In practical applications, rapid prediction and optimization of heat transfer performance are essential for premixed methane impinging flame jets (PMIFJs). This study uses computational fluid dynamics (CFD) combined with a methane detailed chemical reaction mechanism (GRI–Mech 3.0) to study the equivalence ratio (), Reynolds number (Re) of the mixture, and the normalized nozzle–to–plate distance (H/d) on the heat transfer performance of PMIFJs. Moreover, the Kriging model (KM) was used to construct a prediction model of PMIFJ heat transfer performance. A genetic algorithm (GA) was used to determine the maximum likelihood function (MLE) of the model parameters for constructing KM and identify the points with the maximum root mean square error (RMSE) as the new infilled points for surrogate–based optimization (SBO). Combining these methods to analyze the simulation results, the results show that the global heat transfer performance of PMIFJs is enhanced with the increase in , the increase in Re, and the decrease in H/d. Sensitivity analysis points out that Re and significantly affect enhanced heat transfer, while H/d has a relatively small effect. In addition, GA was also used to search for the optimal heat transfer performance, and the global heat transfer performance at specific conditions was significantly enhanced. This study deepens the understanding of the heat transfer mechanism of impinging flame jets and provides an efficient method framework for practical applications. Full article

Due to the high death rate associated with gastric cancer, a great deal of research has been conducted on this disease. The goal of this paper was to start a trimestral review of 2024 for the year that had just started. The scientific literature from 1 January 2024 was chosen with consideration of the the guidelines of the European Society of Medical Oncology (ESMO), which are updated with new findings but not systematically reviewed annually. We used the search term “gastric cancer” to find the most current publications in the PubMed database related to the prognosis and treatment of gastric cancer. As previously said, the only articles that satisfied the inclusion criteria were those from 2024. Articles with case reports were eliminated since they had nothing to do with our research. The treatment of gastric cancer is the focus of the majority of articles from 2024. The primary research axes include surgery and immunonutrition, immunotherapy and Helicobacter pylori, and therapeutic targets. Patients with GC may experience less psychological, social, and financial hardship if the recently identified markers discovered in circulation are better assessed and validated. This could be achieved by either including the markers in an artificial intelligence-based diagnostic score or by using them in conjunction with traditional diagnostic methods. Due to the rising death rate associated with GC, funding for research into diagnosis, prognosis, therapy, and therapeutic targets is essential. Full article

This paper works with functions defined in metric spaces and takes values in complete paranormed vector spaces or in Banach spaces, and proves some necessary and sufficient conditions for weak convergence of probability measures. Our main result is as follows: Let X be a complete paranormed vector space and <!-- MathType@Translator@5@5@MathML2 (no namespace).tdl@MathML 2.0 (no namespace)@ --><math> <semantics> <mi>&#x03A9;</mi> <annotation encoding='MathType-MTEF'>MathType@MTEF@5@5@+= feaahqart1ev3aqatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbWexLMBbXgBd9gzLbvyNv2CaeHbl7mZLdGeaGqiVu0Je9sqqr pepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9vqaqpepm0xbba9pwe9Q8fs 0=yqaqpepae9pg0FirpepeKkFr0xfr=xfr=xb9adbaqaaeGaciGaai aabeqaamaabaabauaakeaacqqHPoWvaaa@40AD@ </annotation> </semantics></math><!-- MathType@End@5@5@ --> an arbitrary metric space, then a sequence <!-- MathType@Translator@5@5@MathML2 (no namespace).tdl@MathML 2.0 (no namespace)@ --><math> <semantics> <mrow> <mo>&#x007B;</mo><msub> <mi>&#x03BC;</mi> <mi>n</mi> </msub> <mo>&#x007D;</mo></mrow> <annotation encoding='MathType-MTEF'>MathType@MTEF@5@5@+= feaahqart1ev3aqatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbWexLMBbXgBd9gzLbvyNv2CaeHbl7mZLdGeaGqiVu0Je9sqqr pepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9vqaqpepm0xbba9pwe9Q8fs 0=yqaqpepae9pg0FirpepeKkFr0xfr=xfr=xb9adbaqaaeGaciGaai aabeqaamaabaabauaakeaacaGG7bGaeqiVd02aaSbaaSqaaiaad6ga aeqaaOGaaiyFaaaa@43FE@ </annotation> </semantics></math><!-- MathType@End@5@5@ --> of probability measures is weakly convergent to a probability measure <!-- MathType@Translator@5@5@MathML2 (no namespace).tdl@MathML 2.0 (no namespace)@ --><math> <semantics> <mi>&#x03BC;</mi> <annotation encoding='MathType-MTEF'>MathType@MTEF@5@5@+= feaahqart1ev3aqatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbWexLMBbXgBd9gzLbvyNv2CaeHbl7mZLdGeaGqiVu0Je9sqqr pepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9vqaqpepm0xbba9pwe9Q8fs 0=yqaqpepae9pg0FirpepeKkFr0xfr=xfr=xb9adbaqaaeGaciGaai aabeqaamaabaabauaakeaacqaH8oqBaaa@40D5@ </annotation> </semantics></math><!-- MathType@End@5@5@ --> if and only if <!-- MathType@Translator@5@5@MathML2 (no namespace).tdl@MathML 2.0 (no namespace)@ --><math> <semantics> <mrow> <munder> <mrow> <mi>lim</mi></mrow> <mrow> <mi>n</mi><mo>&#x2192;</mo><mi>&#x221E;</mi></mrow> </munder> <mstyle displaystyle='true'> <mrow> <msub> <mo>&#x222B;</mo> <mi>&#x03A9;</mi> </msub> <mrow></mrow> </mrow> </mstyle><mi>g</mi><mo stretchy='false'>(</mo><mi>s</mi><mo stretchy='false'>)</mo><mi>d</mi><msubsup> <mi>&#x03BC;</mi> <mi>n</mi> <mrow></mrow> </msubsup> <mo>=</mo><mstyle displaystyle='true'> <mrow> <msub> <mo>&#x222B;</mo> <mi>&#x03A9;</mi> </msub> <mrow></mrow> </mrow> </mstyle><mi>g</mi><mo stretchy='false'>(</mo><mi>s</mi><mo stretchy='false'>)</mo><mi>d</mi><mi>&#x03BC;</mi></mrow> <annotation encoding='MathType-MTEF'>MathType@MTEF@5@5@+= feaahqart1ev3aqatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbWexLMBbXgBd9gzLbvyNv2CaeHbl7mZLdGeaGqiVu0Je9sqqr pepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9vqaqpepm0xbba9pwe9Q8fs 0=yqaqpepae9pg0FirpepeKkFr0xfr=xfr=xb9adbaqaaeGaciGaai aabeqaamaabaabauaakeaadaWfqaqaaiGacYgacaGGPbGaaiyBaaWc baGaamOBaiabgkziUkabg6HiLcqabaGcdaWdraqaaaWcbaGaeuyQdC fabeqdcqGHRiI8aOGaam4zaiaacIcacaWGZbGaaiykaiaadsgacqaH 8oqBdaqhaaWcbaGaamOBaaqaaaaakiabg2da9maapebabaaaleaacq qHPoWvaeqaniabgUIiYdGccaWGNbGaaiikaiaadohacaGGPaGaamiz aiabeY7aTbaa@5BAF@ </annotation> </semantics></math><!-- MathType@End@5@5@ --> for every bounded continuous function g: Ω → X. A special case is as the following: if X is a Banach space, <!-- MathType@Translator@5@5@MathML2 (no namespace).tdl@MathML 2.0 (no namespace)@ --><math> <semantics> <mi>&#x03A9;</mi> <annotation encoding='MathType-MTEF'>MathType@MTEF@5@5@+= feaahqart1ev3aqatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbWexLMBbXgBd9gzLbvyNv2CaeHbl7mZLdGeaGqiVu0Je9sqqr pepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9vqaqpepm0xbba9pwe9Q8fs 0=yqaqpepae9pg0FirpepeKkFr0xfr=xfr=xb9adbaqaaeGaciGaai aabeqaamaabaabauaakeaacqqHPoWvaaa@40AD@ </annotation> </semantics></math><!-- MathType@End@5@5@ --> an arbitrary metric space, then <!-- MathType@Translator@5@5@MathML2 (no namespace).tdl@MathML 2.0 (no namespace)@ --><math> <semantics> <mrow> <mo>&#x007B;</mo><msub> <mi>&#x03BC;</mi> <mi>n</mi> </msub> <mo>&#x007D;</mo></mrow> <annotation encoding='MathType-MTEF'>MathType@MTEF@5@5@+= feaahqart1ev3aqatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbWexLMBbXgBd9gzLbvyNv2CaeHbl7mZLdGeaGqiVu0Je9sqqr pepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9vqaqpepm0xbba9pwe9Q8fs 0=yqaqpepae9pg0FirpepeKkFr0xfr=xfr=xb9adbaqaaeGaciGaai aabeqaamaabaabauaakeaacaGG7bGaeqiVd02aaSbaaSqaaiaad6ga aeqaaOGaaiyFaaaa@43FE@ </annotation> </semantics></math><!-- MathType@End@5@5@ --> is weakly convergent to <!-- MathType@Translator@5@5@MathML2 (no namespace).tdl@MathML 2.0 (no namespace)@ --><math> <semantics> <mi>&#x03BC;</mi> <annotation encoding='MathType-MTEF'>MathType@MTEF@5@5@+= feaahqart1ev3aqatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbWexLMBbXgBd9gzLbvyNv2CaeHbl7mZLdGeaGqiVu0Je9sqqr pepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9vqaqpepm0xbba9pwe9Q8fs 0=yqaqpepae9pg0FirpepeKkFr0xfr=xfr=xb9adbaqaaeGaciGaai aabeqaamaabaabauaakeaacqaH8oqBaaa@40D5@ </annotation> </semantics></math><!-- MathType@End@5@5@ --> if and only if <!-- MathType@Translator@5@5@MathML2 (no namespace).tdl@MathML 2.0 (no namespace)@ --><math> <semantics> <mrow> <munder> <mrow> <mi>lim</mi></mrow> <mrow> <mi>n</mi><mo>&#x2192;</mo><mi>&#x221E;</mi></mrow> </munder> <mstyle displaystyle='true'> <mrow> <msub> <mo>&#x222B;</mo> <mi>&#x03A9;</mi> </msub> <mrow></mrow> </mrow> </mstyle><mi>g</mi><mo stretchy='false'>(</mo><mi>s</mi><mo stretchy='false'>)</mo><mi>d</mi><msubsup> <mi>&#x03BC;</mi> <mi>n</mi> <mrow></mrow> </msubsup> <mo>=</mo><mstyle displaystyle='true'> <mrow> <msub> <mo>&#x222B;</mo> <mi>&#x03A9;</mi> </msub> <mrow></mrow> </mrow> </mstyle><mi>g</mi><mo stretchy='false'>(</mo><mi>s</mi><mo stretchy='false'>)</mo><mi>d</mi><mi>&#x03BC;</mi></mrow> <annotation encoding='MathType-MTEF'>MathType@MTEF@5@5@+= feaahqart1ev3aqatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr 4rNCHbWexLMBbXgBd9gzLbvyNv2CaeHbl7mZLdGeaGqiVu0Je9sqqr pepC0xbbL8F4rqqrFfpeea0xe9Lq=Jc9vqaqpepm0xbba9pwe9Q8fs 0=yqaqpepae9pg0FirpepeKkFr0xfr=xfr=xb9adbaqaaeGaciGaai aabeqaamaabaabauaakeaadaWfqaqaaiGacYgacaGGPbGaaiyBaaWc baGaamOBaiabgkziUkabg6HiLcqabaGcdaWdraqaaaWcbaGaeuyQdC fabeqdcqGHRiI8aOGaam4zaiaacIcacaWGZbGaaiykaiaadsgacqaH 8oqBdaqhaaWcbaGaamOBaaqaaaaakiabg2da9maapebabaaaleaacq qHPoWvaeqaniabgUIiYdGccaWGNbGaaiikaiaadohacaGGPaGaamiz aiabeY7aTbaa@5BAF@ </annotation> </semantics></math><!-- MathType@End@5@5@ --> for every bounded continuous function g: Ω → X. Our theorems and corollaries in the article modified or generalized some recent results regarding the convergence of sequences of measures. Full article

L-asparaginase is an essential drug used to treat acute lymphoid leukemia (ALL), a cancer of high prevalence in children. Several adverse reactions associated with L-asparaginase have been observed, mainly caused by immunogenicity and allergenicity. Some strategies have been adopted, such as searching for new microorganisms that produce the enzyme and applying protein engineering. Therefore, this work aimed to elucidate the molecular structure and predict the immunogenic profile of L-asparaginase from Penicillium cerradense, recently revealed as a new fungus of the genus Penicillium and producer of the enzyme, as a motivation to search for alternatives to bacterial L-asparaginase. In the evolutionary relationship, L-asparaginase from P. cerradense closely matches Aspergillus species. Using in silico tools, we characterized the enzyme as a protein fragment of 378 amino acids (39 kDa), including a signal peptide containing 17 amino acids, and the isoelectric point at 5.13. The oligomeric state was predicted to be a homotetramer. Also, this L-asparaginase presented a similar immunogenicity response (T- and B-cell epitopes) compared to Escherichia coli and Dickeya chrysanthemi enzymes. These results suggest a potentially useful L-asparaginase, with insights that can drive strategies to improve enzyme production. Full article

Erythropoiesis is initiated with the transformation of multipotent hematopoietic stem cells into committed erythroid progenitor cells in the erythroblastic islands of the bone marrow in adults. These cells undergo several stages of differentiation, including erythroblast formation, normoblast formation, and finally, the expulsion of the nucleus to form mature red blood cells. The erythropoietin (EPO) pathway, which is activated by hypoxia, induces stimulation of the erythroid progenitor cells and the promotion of their proliferation and survival as well as maturation and hemoglobin synthesis. The regulation of erythropoiesis is a complex and dynamic interaction of a myriad of factors, such as transcription factors (GATA-1, STAT5), cytokines (IL-3, IL-6, IL-11), iron metabolism and cell cycle regulators. Multiple microRNAs are involved in erythropoiesis, mediating cell growth and development, regulating oxidative stress, erythrocyte maturation and differentiation, hemoglobin synthesis, transferrin function and iron homeostasis. This review aims to explore the physiology of steady-state erythropoiesis and to outline key mechanisms involved in ineffective erythropoiesis linked to anemia, chronic inflammation, stress, and hematological malignancies. Studying aberrations in erythropoiesis in various diseases allows a more in-depth understanding of the heterogeneity within erythroid populations and the development of gene therapies to treat hematological disorders. Full article

Increasing attention is being given to reduce the specific energy consumption in desalination processes, which translates into greater use of exergy analysis. An exergetic analysis provides relevant information related to the influence of the efficiency of a single component in the global plant performance and in the exergy cost of the product. Therefore, an exergy analysis identifies the main improvement potentials in a productive thermodynamic process. Related to desalination technologies, many previous papers deal with the calculation of the parameters involved in the exergy analysis, the exergetic efficiency of different processes, plants, and technologies among them. However, different approaches for formulating the exergetic efficiency have been suggested in the literature, often without sufficient understanding and consistency. In this work, these formulations, applied to the main desalination components and processes, are compared and critically reviewed. Two definitions of exergy efficiency are applied to the desalination components of the three main thermal desalination processes (multieffect distillation–thermal vapour compression, multistage flash distillation, and direct-contact membrane distillation). The results obtained for the exergy efficiency of the MED-TVC, MSF, and DCMD processes for the input–output approach are 21.35%, 17.08%, and 1.28%, respectively, compared to the consumed–produced approach that presented 3.1%, 1.58%, and 0.37%, respectively. The consumed–produced approach seems to better fit the thermodynamic behaviour of thermal desalination systems. Full article

Calcitonin gene-related peptide (CGRP) has long been implicated in both the physiology and pathophysiology of the respiratory tract. The objective of our study was to determine the serum concentration of alpha CGRP (αCGRP) in cystic fibrosis (CF) that arises from mutations in the gene responsible for encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Currently, there are not many data in the literature about the role of CGRP in CF. The serum level of αCGRP was estimated using the enzyme-linked immunosorbent assay among 64 patients with CF and 31 healthy controls. The αCGRP concentration in the CF group was 62.51 ± 15.45 pg/mL, while in the control group it was 47.43 ± 8.06 pg/mL (p < 0.001). We also compared the level of αCGRP in CF patients according to the type of CFTR mutation. Homozygotes for ΔF508 had higher αCGRP levels than heterozygotes (67.9 ± 10.2 vs. 54.5 ± 18.3 pg/mL, p < 0.01). The level of this neuropeptide was statistically higher in patients with severe disease than in those with mild CF (p = 0.003) when patients were divided into three groups by spirometry results. αCGRP concentration was not correlated with age, sex, clinical parameters, and pulmonary function test results in the study participants. The results of our study suggest a significant increase in the concentration of αCGRP in the serum of patients with CF compared to the control group. This observation opens interesting possibilities for understanding the role of αCGRP in the context of CF pathophysiology. Full article

In recent years, kaempferol, a natural flavonoid present in various fruits and vegetables, has received significant attention in gastrointestinal cancer research due to its varied therapeutic effects. Kaempferol has been proven to alter several molecular mechanisms and pathways, such as the PI3/Akt, mTOR, and Erk/MAPK pathway involved in cancer progression, showing its inhibitory effects on cell proliferation, survival, angiogenesis, metastasis, and migration. Kaempferol is processed in the liver and small intestine, but limited bioavailability has been a major concern in the clinical implications of kaempferol. Nano formulations have been proven to enhance kaempferol’s efficacy in cancer prevention. The synergy of nanotechnology and kaempferol has shown promising results in in vitro studies, highlighting the importance for more in vivo research and clinical trials to determine safety and efficacy. This review aims to focus on the role of kaempferol in various types of gastrointestinal cancer and how the combination of kaempferol with nanotechnology helps in improving therapeutic efficacy in cancer treatment. Full article

Objective: The vast majority of gastrointestinal stromal tumors (GISTs) are driven by activating mutations in KIT, PDGFRA, or components of the succinate dehydrogenase (SDH) complex (SDHA, SDHB, SDHC, and SDHD genes). A small fraction of GISTs lack alterations in KIT, PDGFRA, and SDH. We aimed to further characterize the clinical and genomic characteristics of these so-called “triple-negative” GISTs. Methods: We extracted clinical and genomic data from patients seen at MD Anderson Cancer Center with a diagnosis of GIST and available clinical next generation sequencing data to identify “triple-negative” patients. Results: Of the 20 patients identified, 11 (55.0%) had gastric, 8 (40.0%) had small intestinal, and 1 (5.0%) had rectal primary sites. In total, 18 patients (90.0%) eventually developed recurrent or metastatic disease, and 8 of these presented with de novo metastatic disease. For the 13 patients with evaluable response to imatinib (e.g., neoadjuvant treatment or for recurrent/metastatic disease), the median PFS with imatinib was 4.4 months (range 0.5–191.8 months). Outcomes varied widely, as some patients rapidly developed progressive disease while others had more indolent disease. Regarding potential genomic drivers, four patients were found to have alterations in the RAS/RAF/MAPK pathway: two with a BRAF V600E mutation and two with NF1 loss-of-function (LOF) mutations (one deletion and one splice site mutation). In addition, we identified two with TP53 LOF mutations, one with NTRK3 fusion (ETV6-NTRK3), one with PTEN deletion, one with FGFR1 gain-of-function (GOF) mutation (K654E), one with CHEK2 LOF mutation (T367fs*), one with Aurora kinase A fusion (AURKA-CSTF1), and one with FANCA deletion. Patients had better responses with molecularly targeted therapies than with imatinib. Conclusions: Triple-negative GISTs comprise a diverse cohort with different driver mutations. Compared to KIT/PDGFRA-mutant GIST, limited benefit was observed with imatinib in triple-negative GIST. In depth molecular profiling can be helpful in identifying driver mutations and guiding therapy. Full article

Stress is an important risk factor for the onset of anxiety and depression. The ability to cope with stressful events varies among different subjects, probably depending on different genetic variants, sex and previous life experiences. The Val66Met variant of Brain-Derived Neurotrophic Factor (BDNF), which impairs the activity-dependent secretion of BDNF, has been associated with increased susceptibility to the development of various neuropsychiatric disorders. Adult male and female wild-type Val/Val (BDNF^V/V) and heterozygous Val/Met (BDNF^V/M) mice were exposed to two sessions of forced swimming stress (FSS) per day for two consecutive days. The mice were behaviorally tested 1 day (short-term effect) or 11 days (long-term effect) after the last stress session. Protein and mRNA levels were measured in the hippocampus 16 days after the end of stress exposure. Stressed mice showed a higher anxiety-like phenotype compared to non-stressed mice, regardless of the sex and genotype, when analyzed following the short period of stress. In the prolonged period, anxiety-like behavior persisted only in male BDNF^V/M mice (p < 0.0001). Interestingly, recovery in male BDNF^V/V mice was accompanied by an increase in pCREB (p < 0.001) and Bdnf4 (p < 0.01) transcript and a decrease in HDAC1 (p < 0.05) and Dnmt3a (p = 0.01) in the hippocampus. Overall, our results show that male and female BDNF Val66Met knock-in mice can recover from subchronic stress in different ways. Full article

Background and Objectives: No comparative study has evaluated the inter-method agreement and reliability between Heuron AD and other clinically available brain volumetric software packages. Hence, we aimed to investigate the inter-method agreement and reliability of three clinically available brain volumetric software packages: FreeSurfer (FS), NeuroQuant^® (NQ), and Heuron AD (HAD). Materials and Methods: In this study, we retrospectively included 78 patients who underwent conventional three-dimensional (3D) T1-weighed imaging (T1WI) to evaluate their memory impairment, including 21 with normal objective cognitive function, 24 with mild cognitive impairment, and 33 with Alzheimer’s disease (AD). All 3D T1WI scans were analyzed using three different volumetric software packages. Repeated-measures analysis of variance, intraclass correlation coefficient, effect size measurements, and Bland–Altman analysis were used to evaluate the inter-method agreement and reliability. Results: The measured volumes demonstrated substantial to almost perfect agreement for most brain regions bilaterally, except for the bilateral globi pallidi. However, the volumes measured using the three software packages showed significant mean differences for most brain regions, with consistent systematic biases and wide limits of agreement in the Bland–Altman analyses. The pallidum showed the largest effect size in the comparisons between NQ and FS (5.20–6.93) and between NQ and HAD (2.01–6.17), while the cortical gray matter showed the largest effect size in the comparisons between FS and HAD (0.79–1.91). These differences and variations between the software packages were also observed in the subset analyses of 45 patients without AD and 33 patients with AD. Conclusions: Despite their favorable reliability, the software-based brain volume measurements showed significant differences and systematic biases in most regions. Thus, these volumetric measurements should be interpreted based on the type of volumetric software used, particularly for smaller structures. Moreover, users should consider the replaceability-related limitations when using these packages in real-world practice. Full article

The high affinity of the biotin–streptavidin interaction has made this non-covalent coupling an indispensable strategy for the immobilization and enrichment of biomolecular affinity reagents. However, the irreversible nature of the biotin–streptavidin bond renders surfaces functionalized using this strategy permanently modified and not amenable to regeneration strategies that could increase assay reusability and throughput. To increase the utility of biotinylated targets, we here introduce a method for reversibly immobilizing biotinylated thrombin-binding aptamers onto a Ni-nitrilotriacetic acid (Ni-NTA) sensor chip using 6xHis-tagged streptavidin as a regenerable capture ligand. This approach enabled the reproducible immobilization of aptamers and measurements of aptamer–protein interaction in a surface plasmon resonance assay. The immobilized aptamer surface was stable during five experiments over two days, despite the reversible attachment of 6xHis-streptavidin to the Ni-NTA surface. In addition, we demonstrate the reproducibility of this immobilization method and the affinity assays performed using it. Finally, we verify the specificity of the biotin tag–streptavidin interaction and assess the efficiency of a straightforward method to regenerate and reuse the surface. The method described here will allow researchers to leverage the versatility and stability of the biotin–streptavidin interaction while increasing throughput and improving assay efficiency. Full article

Three-dimensional integrated circuits can significantly mitigate the challenges posed by shrinking feature sizes and enable heterogeneous integration. This paper focuses on the 3D floorplanning problem. We formulate it as a multi-objective optimization issue and employ multi-objective simulated annealing to simultaneously optimize area, wirelength and number of vias. During the optimization process, neighboring solutions are explored in the design space through inter-layer or intra-layer perturbations, and decision criteria for the exploration process are formulated based on the dominance relationship of solutions. Test results on the GSRC benchmark demonstrate that our approach delivers superior performance in optimizing area and wirelength. Compared to 2D floorplanning, our method reduces the area by approximately 49% and the wirelength by 21%. Compared to other similar 3D floorplanning methods, we raise the success rate in satisfying the fixed-outline constraint to 100% and improve the wirelength by 3%. The multi-objective simulated annealing method proposed in this paper can effectively address the 3D floorplanning problem. Full article

Internal discharge and overheating faults in sulfur hexafluoride (SF₆) gas-insulated electrical equipment will generate a series of characteristic gas products. Hydrogen fluoride (HF) is one of the main decomposition gases under discharge failure. Because of its extremely corrosive nature, it can react with other materials in gas-insulated switchgear (GIS), resulting in a short existence time, so it needs to be detected online. Resonant gas photoacoustic spectroscopy has the advantage of high sensitivity, fast response, and no sample gas consumption, and can be used for the online detection of flowing gas. In this paper, a simulated GIS corona discharge experimental platform was built, and the HF generated in the discharge was detected online by gas photoacoustic spectroscopy. The absorption peak of HF molecule near 1312.59 nm was selected as the absorption spectral line, and a resonant photoacoustic cell was designed. To improve the detection sensitivity of HF, wavelength modulation and second-harmonic detection technology were used. The online monitoring of HF in the simulated GIS corona discharge fault was successfully realized. The experimental results show that the sensitivity of the designed photoacoustic spectroscopy detection system for HF is 0.445 μV/(μL/L), and the limit of detection (LOD) is 0.611 μL/L. Full article

The general requirements of China’s rural revitalization strategy are industrial prosperity, ecological livability and rich life. However, the traditional livestock breeding model has struggled to balance the dual requirements of production development and ecological protection, and it is urgent to inject new impetus and explore new development paths. At present, e-commerce has become a bridge between pastoral areas and cities, herdsmen and consumers. E-commerce participation is not only an important starting point for herdsmen to increase the added value and profit space of livestock products, but also an effective way to change the original breeding behavior based on the premise of destroying grassland. Therefore, this paper presents an in-depth study on the issue of e-commerce enabling grassland ecological restoration, aiming to provide more scientific and effective guidance for e-commerce to be used to achieve a win–win situation in economy and ecology. Therefore, based on the data of 271 herdsmen in pastoral areas of Inner Mongolia, we used the OLS model and the two-stage least squares (2SLS) method to identify the direct impact of herdsmen’s e-commerce participation on grassland utilization pressure. The empirical results show that e-commerce participation can significantly decrease the grassland utilization pressure. The conclusion was still valid after alleviating endogeneity and conducting a robustness test. The results of a mechanism analysis suggest that the reduction effect of e-commerce participation on grassland utilization pressure is mainly due to price incentive, reputation incentive and place identity. Subjective norms can strengthen the inhibitory effect of e-commerce participation on grassland utilization pressure. Furthermore, a heterogeneity analysis demonstrates that e-commerce participation has a better, decreased impact on the grassland utilization pressure on the banners of China’s rural e-commerce demonstration county program. Under a counterfactual assumption, if herdsmen who can participate in e-commerce choose not to do this, their grassland utilization pressure will increase. Full article

Prior research has suggested that resistance exercise may result in a temporary decrease in vascular function, as measured by flow-mediated dilation (FMD), among untrained young individuals. However, the immediate impact of combined elastic and weight resistance training on older adults remains insufficiently explored. We assessed vascular function before, after, and 30 min after acute exercise under three resistance conditions to evaluate whether a combination of weight and elastic resistance exercises has an acute effect on vascular function in older adults. Fourteen older adults (65.6 ± 2.9 years) executed three sets of 12 repetitions at 65% of one repetition maximum (1 RM) of the bench press (BP) exercise. Testing was performed on three separate days as follows: (1) barbell alone (BA); (2) barbell plus elastic bands (10% of 65% 1 RM) (BE10); and (3) barbell plus elastic bands (20% of 65% 1 RM) (BE20). A two-way (time × condition) repeated measures analysis of variance was employed to assess the time and condition effects on flow-mediated dilation (FMD) and pulse wave velocity (PWV). At 0 min post-exercise, FMD was significantly higher during BE10 than during BA (p < 0.05); however, at 30 min post-exercise, no significant difference (p ≥ 0.05) was observed between the three conditions. In each condition, FMD results did not differ significantly at different times (p ≥ 0.05). For FMD, the main effect of the condition (F[2,26] = 3.86, p = 0.034) and that of the time and condition (F[4,52] = 3.66, p = 0.011) were significant. For PWV, only the difference between the BA and BE10 conditions was significant at 0 min (p < 0.05). PWV increased from baseline in the BA condition (p < 0.05) but not significantly in the BE10 and BE20 conditions (p ≥ 0.05). Therefore, BA, BE10, and BE20 demonstrated various changes in vascular function. Long-term training intervention studies are needed to validate these findings. Full article

Parkinson’s disease (PD) significantly impacts millions of individuals worldwide. Although our understanding of the genetic foundations of PD has advanced, a substantial portion of the genetic variation contributing to disease risk remains unknown. Current PD genetic studies have primarily focused on one form of genetic variation, single nucleotide variants (SNVs), while other important forms of genetic variation, such as structural variants (SVs), are mostly ignored due to the complexity of detecting these variants with traditional sequencing methods. Yet, these forms of genetic variation play crucial roles in gene expression and regulation in the human brain and are causative of numerous neurological disorders, including forms of PD. This review aims to provide a comprehensive overview of our current understanding of the involvement of coding and noncoding SVs in the genetic architecture of PD. Full article

Background and Objectives: This review systematically evaluates the potential of electrical neuromodulation techniques—vagus nerve stimulation (VNS), sacral nerve stimulation (SNS), and tibial nerve stimulation (TNS)—as alternative treatments for inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s Disease (CD). It aims to synthesize current evidence on the efficacy and safety of these modalities, addressing the significant burden of IBD on patient quality of life and the limitations of existing pharmacological therapies. Materials and Methods: We conducted a comprehensive analysis of studies from PubMed, focusing on research published between 1978 and 2024. The review included animal models and clinical trials investigating the mechanisms, effectiveness, and safety of VNS, SNS, and TNS in IBD management. Special attention was given to the modulation of inflammatory responses and its impact on gastrointestinal motility and functional gastrointestinal disorders associated with IBD. Results: Preliminary findings suggest that VNS, SNS, and TNS can significantly reduce inflammatory markers and improve symptoms in IBD patients. These techniques also show potential in treating related gastrointestinal disorders during IBD remission phases. However, the specific mechanisms underlying these benefits remain to be fully elucidated, and there is considerable variability in treatment parameters. Conclusions: Electrical neuromodulation holds promise as a novel therapeutic avenue for IBD, offering an alternative to patients who do not respond to traditional treatments or experience adverse effects. The review highlights the need for further rigorous studies to optimize stimulation parameters, understand long-term outcomes, and integrate neuromodulation effectively into IBD treatment protocols. Full article

Altitude plays a crucial role in shaping the diversity and distribution of species in forest landscapes in mountainous regions. However, existing studies often lack comprehensive analysis of the intricate relationships among environmental factors, disturbances, and species diversity. This study aims to address this gap by thoroughly analyzing major species’ diversity, distribution, and regeneration status, along with their influencing factors, across different altitudinal gradients (1850 to 2350 m). Field surveys were conducted to examine the major species in different vegetation layers of the secondary Picea forest in Guandi Mountain. The key findings from the study include the following: (1) the study area recorded a total of nine species of adult trees, belonging to eight genera in five families, fourteen species of shrubs from eight genera in five families, and fifty-two herb species representing forty-eight genera in twenty-six families. Dominant species varied across layers, with Picea asperata Mast. and Larix principis-rupprechtii Mayr. dominating the arborous layer, Lonicera ferdinandii Franch. and Cotoneaster acutifolius Turcz. in the shrub layer, and Poa pratensis L. and Duchesnea indica (Andrews.) Focke in the herb layer. (2) Altitude significantly influenced species diversity, with the most pronounced effects observed in the shrub and herb layers. (3) Tree species regeneration varied with altitude, with Picea asperata exhibiting the highest regeneration performance, particularly in the high-altitude zone (2250–2350 m). Regeneration parameters were significantly correlated with species diversity indices in both tree and shrub layers. (4) Redundancy analysis revealed that, apart from altitude, cutting (p = 0.015) influenced the species diversity of the tree layer, while annual precipitation (p = 0.006) and temperature (p = 0.01) determined the diversity of the shrub layer. Grazing (p = 0.042) was identified as a determining factor for species diversity in the herb layer. Overall, these findings provide valuable insights into the sustainable management of forest ecosystems in the study area and offer practical guidance for forest management in similar mountainous landscapes worldwide. Full article

α7 nicotinic acetylcholine receptors (nAChRs) are mainly distributed in the central nervous system (CNS), including the hippocampus, striatum, and cortex of the brain. The α7 nAChR has high Ca²⁺ permeability and can be quickly activated and desensitized, and is closely related to Alzheimer’s disease (AD), epilepsy, schizophrenia, lung cancer, Parkinson’s disease (PD), inflammation, and other diseases. α-conotoxins from marine cone snail venom are typically short, disulfide-rich neuropeptides targeting nAChRs and can distinguish various subtypes, providing vital pharmacological tools for the functional research of nAChRs. [Q1G, ΔR14]LvΙB is a rat α7 nAChRs selective antagonist, modified from α-conotoxin LvΙB. In this study, we utilized three types of fluorescein after N-Hydroxy succinimide (NHS) activation treatment: 6-TAMRA-SE, Cy3 NHS, and BODIPY-FL NHS, labeling the N-Terminal of [Q1G, ΔR14]LvΙB under weak alkaline conditions, obtaining three fluorescent analogs: LvIB-R, LvIB-C, and LvIB-B, respectively. The potency of [Q1G, ΔR14]LvΙB fluorescent analogs was evaluated at rat α7 nAChRs expressed in Xenopus laevis oocytes. Using a two-electrode voltage clamp (TEVC), the half-maximal inhibitory concentration (IC₅₀) values of LvIB-R, LvIB-C, and LvIB-B were 643.3 nM, 298.0 nM, and 186.9 nM, respectively. The stability of cerebrospinal fluid analysis showed that after incubation for 12 h, the retention rates of the three fluorescent analogs were 52.2%, 22.1%, and 0%, respectively. [Q1G, ΔR14]LvΙB fluorescent analogs were applied to explore the distribution of α7 nAChRs in the hippocampus and striatum of rat brain tissue and it was found that Cy3- and BODIPY FL-labeled [Q1G, ΔR14]LvΙB exhibited better imaging characteristics than 6-TAMARA-. It was also found that α7 nAChRs are widely distributed in the cerebral cortex and cerebellar lobules. Taking into account potency, imaging, and stability, [Q1G, ΔR14]LvΙB -BODIPY FL is an ideal pharmacological tool to investigate the tissue distribution and function of α7 nAChRs. Our findings not only provide a foundation for the development of conotoxins as visual pharmacological probes, but also demonstrate the distribution of α7 nAChRs in the rat brain. Full article

A retrospective study at the 4th Military Clinical Hospital in Wroclaw, Poland, assessed PCR testing alongside blood cultures to guide antimicrobial therapy decisions in hospitalized patients, to determine how much time the results of the molecular tests preceded conventional methods. Among 118 patients, Staphylococcus aureus (37%) and Escherichia coli (21%) were the most common bloodstream infection agents. Blood cultures utilized the BacT/ALERT 3D system, and molecular diagnostics were conducted using the FilmArray platform with the BIOFIRE BCID2 panel. Methicillin susceptibility was observed in 66% of S. aureus strains, while 26% of Gram-negative bacilli exhibited an ESBL phenotype. Therapeutic decisions based on molecular test results were often incorrect for S. aureus infections, particularly MSSA (64.5%), but generally accurate for Gram-negative bacilli. The median times from positive blood culture to BCID2 and pathogen identification/susceptibility were 10 h and 52 h, respectively. Molecular diagnostics facilitated faster initiation of appropriate antibiotic therapy, highlighting the need to educate medical staff on proper interpretation. Consulting within an antimicrobial stewardship program (ASP) could enhance the benefits of implementing molecular methods in bloodstream infection diagnostics. Full article

Even though inhalation dosimetry is determined by three factors (i.e., breathing, aerosols, and the respiratory tract), the first two categories have been more widely studied than the last. Both breathing and aerosols are quantitative variables that can be easily changed, while respiratory airway morphologies are difficult to reconstruct, modify, and quantify. Although several methods are available for model reconstruction and modification, developing an anatomically accurate airway model and morphing it to various physiological conditions remains labor-intensive and technically challenging. The objective of this study is to explore the feasibility of using an adjoint–CFD model to understand airway shape effects on vapor deposition and control vapor flux into the lung. A mouth–throat model was used, with the shape of the mouth and tongue being automatically varied via adjoint morphing and the vapor transport being simulated using ANSYS Fluent coupled with a wall absorption model. Two chemicals with varying adsorption rates, Acetaldehyde and Benzene, were considered, which exhibited large differences in dosimetry sensitivity to airway shapes. For both chemicals, the maximal possible morphing was first identified and then morphology parametric studies were conducted. Results show that changing the mouth–tongue shape can alter the oral filtration by 3.2% for Acetaldehyde and 0.27% for Benzene under a given inhalation condition. The front tongue exerts a significant impact on all cases considered, while the impact of other regions varies among cases. This study demonstrates that the hybrid adjoint–CFD approach can be a practical and efficient method to investigate morphology-associated variability in the dosimetry of vapors and nanomedicines under steady inhalation. Full article