Heme biosynthesis is a highly conserved pathway from bacteria to higher animals. Heme, which serves as a prosthetic group for various enzymes involved in multiple biochemical processes, is essential in almost all species, making heme homeostasis vital for life. However, studies on the biological functions of heme in filamentous fungi are scarce. In this study, we investigated the role of heme in Fusarium graminearum. A mutant lacking the rate-limiting enzymes in heme synthesis, coproporphyrinogen III oxidase (Cpo) or ferrochelatase (Fc), was constructed using a homologous recombination strategy. The results showed that the absence of these enzymes was lethal to F. graminearum, but the growth defect could be rescued by the addition of hemin, so we carried out further studies with the help of hemin. The results demonstrated that heme was required for the activity of FgCyp51, and its absence increased the sensitivity to tebuconazole and led to the upregulation of FgCYP51 in F. graminearum. Additionally, heme plays an indispensable role in the life cycle of F. graminearum, which is essential for vegetative growth, conidiation, external stress response (especially oxidative stress), lipid accumulation, fatty acid β-oxidation, autophagy, and virulence. Full article

Amidst an unprecedented period of technological progress, incorporating digital platforms into diverse domains of existence has become indispensable, fundamentally altering the operational processes of governments, businesses, and individuals. Nevertheless, the swift process of digitization has concurrently led to the emergence of cybercrime, which takes advantage of weaknesses in interconnected systems. The growing dependence of society on digital communication, commerce, and information sharing has led to the exploitation of these platforms by malicious actors for hacking, identity theft, ransomware, and phishing attacks. With the growing dependence of organizations, businesses, and individuals on digital platforms for information exchange, commerce, and communication, malicious actors have identified the susceptibilities present in these systems and have begun to exploit them. This study examines 28 research papers focusing on intrusion detection systems (IDS), and phishing detection in particular, and how quickly responses and detections in cybersecurity may be made. We investigate various approaches and quantitative measurements to comprehend the link between reaction time and detection time and emphasize the necessity of minimizing both for improved cybersecurity. The research focuses on reducing detection and reaction times, especially for phishing attempts, to improve cybersecurity. In smart grids and automobile control networks, faster attack detection is important, and machine learning can help. It also stresses the necessity to improve protocols to address increasing cyber risks while maintaining scalability, interoperability, and resilience. Although machine-learning-based techniques have the potential for detection precision and reaction speed, obstacles still need to be addressed to attain real-time capabilities and adjust to constantly changing threats. To create effective defensive mechanisms against cyberattacks, future research topics include investigating innovative methodologies, integrating real-time threat intelligence, and encouraging collaboration. Full article

Botulinum neurotoxins E (BoNT/E) and A (BoNT/A) act by cleaving Synaptosome-Associated Protein 25 (SNAP25) at two different C-terminal sites, but they display very distinct durations of action, BoNT/E being short acting and BoNT/A long acting. We investigated the duration of action, spread and neuronal transport of BoNT/E (6.5 ng/kg) and BoNT/A (125 pg/kg) after single intramuscular administrations of high equivalent efficacious doses, in rats, over a 30- or 75-day periods, respectively. To achieve this, we used (i) digit abduction score assay, (ii) immunohistochemistry for SNAP25 (N-ter part; SNAP25^N-ter and C-ter part; SNAP25^C-ter) and its cleavage sites (cleaved SNAP25; c-SNAP25^E and c-SNAP25^A) and (iii) muscular changes in histopathology evaluation. Combined in vivo observation and immunohistochemistry analysis revealed that, compared to BoNT/A, BoNT/E induces minimal muscular changes, possesses a lower duration of action, a reduced ability to spread and a decreased capacity to be transported to the lumbar spinal cord. Interestingly, SNAP25^C-ter completely disappeared for both toxins during the peak of efficacy, suggesting that the persistence of toxin effects is driven by the persistence of proteases in tissues. These data unveil some new molecular mechanisms of action of the short-acting BoNT/E and long-acting BoNT/A, and reinforce their overall safety profiles. Full article

In the past few decades, considerable scientific strides have been made in the subject of drug analysis in human biological samples. However, the risk caused by incorrect drug plasma levels in patients still remains an important concern. This review paper attempts to investigate the advances made over the last ten years in common sample preparation techniques (SPT) for biological samples based on solid sorbents, including solid-phase extraction (SPE) and solid-phase micro-extraction (SPME), and in particular in the field of molecularly imprinted polymers (MIPs), including non-stimuli-responsive and stimuli-responsive adsorbents. This class of materials is known as ‘smart adsorbents’, exhibiting tailored responses to various stimuli such as magnetic fields, pH, temperature, and light. Details are provided on how these advanced SPT are changing the landscape of modern drug analysis in their coupling with liquid chromatography-mass spectrometry (LC-MS) analytical techniques, a general term that includes high-performance liquid chromatography (HPLC) and ultra-high performance liquid chromatography (UHPLC), as well as any variation of MS, such as tandem (MS/MS), multiple-stage (MSⁿ), and high-resolution (HRMS) mass spectrometry. Some notes are also provided on coupling with less-performing techniques, such as high-performance liquid chromatography with ultraviolet (HPLC-UV) and diode array detection (HPLC-DAD) detection. Finally, we provide a general review of the difficulties and benefits of the proposed approaches and the future prospects of this research area. Full article

Mesoscale eddies are ubiquitous oceanic phenomena and play an important role in ocean circulation, ocean dynamics, and the transport of material energy. Temperature anomalies are a crucial parameter that reflects the state of mesoscale eddies. This study proposes a Gaussian function model to fit the vertical temperature anomaly (TA) profile to facilitate the analysis of variations, and the principle of the model is based on the fact that each TA profile tends to fluctuate around one or more peaks. The model is extracted and validated using Argo profiles within cyclonic and anticyclonic eddies in the Northwest Pacific Ocean spanning over the period from 2002 to 2021. The validation demonstrates that the model can accurately recover the vertical TA profiles with a limited number of parameters. This makes it suitable for analysing the spatial distribution patterns that require a large sample count. The analysis indicates that eddies with different TA profiles have a spatial aggregation effect in geographic distribution. Eddies with lower extreme temperature anomalies, at depths of 200–300 m, are mainly distributed along two bands on the north side of the Kuroshio Extension (KE) and the North Equatorial Current. Eddies with extreme TAs at the deepest depth (500–600 m) are distributed along the KE. Full article

The outdoor thermal environment (OTE) is closely related to sustainable urban development and human living, and related research has attracted widespread attention. The research hotspots and research frontiers were obtained using CiteSpace to analyze 4473 relevant studies published in English from the Web of Science (WOS) core database from 1998 to 2023. The results show that (1) Hong Kong Polytechnic University, National University of Singapore, Chinese Academy of Sciences, Tsinghua University, and Harbin Institute of Technology are important in OTE research. China has the largest number of publications in the field of OTE, but the United States has the greatest centrality and significant influence. (2) The focus of OTE keyword clustering research is divided into four main categories: thermal environment perception, the thermal environment index, thermal environment quality, and thermal environment optimization. (3) The frontiers of OTE research have changed from focusing on environmental quality, thermal perception, numerical simulation, urban space, and thermal adaptation to thermal mitigation, energy conservation, energy consumption, and optimization strategies. Visualization research in the field of OTE helps to provide references for the direction of future research on improving climate change, human thermal comfort, urban planning, and pre-planning. Full article

Anterior commissure is involved in about 20% of early-stage glottic squamous cell carcinomas (EGSCCs). Treatment outcomes and prognostic factors for EGSCC with anterior commissure involvement (ACI) were evaluated by focusing on hyperfractionated radiotherapy (74.4 Gy in 62 fractions). One-hundred and fifty-three patients with T1–T2 EGSCC were included in this study. The median total doses for T1a, T1b, and T2 were 66, 74.4, and 74.4 Gy, respectively. Overall, 49 (32%) patients had T1a, 38 (25%) had T1b, and 66 (43%) had T2 disease. The median treatment duration was 46 days. The median follow-up duration was 5.1 years. The 10-year overall and cause-specific survival rates were 72% and 97%, respectively. The 10-year local control rates were 94% for T1a, 88% for T1b, and 81% for T2 disease. Local control rates in patients with ACI were slightly better than those in patients without ACI with T1a and T1b diseases; however, the difference was not significant. The 10-year laryngeal preservation rate was 96%. Six patients experienced grade 3 mucositis, and four patients had grade 3 dermatitis. Hyperfractionated radiotherapy was effective for T1 disease with ACI, but insufficient for T2 disease with ACI. Our treatment strategy resulted in excellent laryngeal preservation. Full article

It is known that ginger oleoresin contains various active components and possesses bioactivities. In this study, ginger oleoresin from Chinese ginger (Zingiber officinale var. roscoe) was extracted using a CO₂ supercritical fluid extraction method with a 0.52% yield (g/g), based on dry weights. Zingiberene with a content of 51.6 mg/g was the main volatile in the ginger oleoresin. In total, 17 phenolic compounds were identified, and their contents were calculated as 587.54 mg/g. Among them, a new gingertriol was detected in the Z. officinale. Antioxidant activity tests showed that the ginger oleoresin and six gingerols exhibited strong scavenging free radical activities, and the zingerone exhibited the strongest antioxidant activity, with IC₅₀ values of 11.3 µg/mL for the 2, 2′-diphenyl-1-picrylhydrazyl radical and 19.0 µg/mL for the 2, 2′-amino-di (2-ethyl-benzothiazoline sulphonic acid-6) ammonium salt radical cation, comparable to vitamin C. Ginger oleoresin inhibits HGC-27 human gastric cancer cell proliferation at a rate of 4.05~41.69% and induces cell apoptosis at a rate of 10.4~20.9%. The Western blot result demonstrated that the AKT signaling pathway has the potential mechanism of ginger oleoresin acting on HGC-27 cells. The anticancer potential of the gingerol standards on HGC-27 cells followed the order of 8-gingerol > 6-gingerol > 10-gingerol > zingerone. The different antioxidant and anticancer potentials of the ginger phenolic compounds could be attributed to the presence of hydroxyl groups in the unbranched 1-alkyl chain and the length of carbon side chain. Consequently, ginger oleoresin shows substantial antioxidant and anticancer therapeutic potential and can be used for novel food–drug development. Full article

TAFRO syndrome is an acute systemic inflammatory disorder characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis, renal dysfunction, and organomegaly. While its lymph node pathology is similar to that of idiopathic multicentric Castleman disease (iMCD), the clinical features of TAFRO syndrome differ from those of typical iMCD, as they include a more aggressive clinical course and high mortality. However, an optimal treatment strategy for TAFRO syndrome has not yet been established, owing to a poor understanding of its pathogenesis. The limited cases we encountered suggest that tacrolimus treatment in combination with glucocorticoids may potentially be effective and well tolerated as an initial treatment, and hold promise as a glucocorticoid-sparing agent. Herein, we report an additional case and review the sparse literature available regarding TAFRO syndrome treated via tacrolimus. Full article

Multiple myeloma (MM) is the second most common hematological malignancy, which remains incurable despite recent advances in treatment strategies. Like other forms of cancer, MM is characterized by genomic instability, caused by defects in DNA repair. Along with mutations in DNA repair genes and genotoxic drugs used to treat MM, non-canonical secondary DNA structures (four-stranded G-quadruplex structures) can affect accumulation of somatic mutations and chromosomal abnormalities in the tumor cells of MM patients. Here, we tested the hypothesis that G-quadruplex structures may influence the distribution of somatic mutations in the tumor cells of MM patients. We sequenced exomes of normal and tumor cells of 11 MM patients and analyzed the data for the presence of G4 context around points of somatic mutations. To identify molecular mechanisms that could affect mutational profile of tumors, we also analyzed mutational signatures in tumor cells as well as germline mutations for the presence of specific SNPs in DNA repair genes or in genes regulating G-quadruplex unwinding. In several patients, we found that sites of somatic mutations are frequently located in regions with G4 context. This pattern correlated with specific germline variants found in these patients. We discuss the possible implications of these variants for mutation accumulation and specificity in MM and propose that the extent of G4 context enrichment around somatic mutation sites may be a novel metric characterizing mutational processes in tumors. Full article

In this article, we demonstrate a high-energy, wide-spectrum, spatiotemporal mode-locked (STML) fiber laser. Unlike traditional single-mode fiber lasers, STML fiber lasers theoretically enable mode-locking with various combinations of transverse modes. The laser can deliver two different STML pulse sequences with different pulse widths, spectra and beam profiles, due to the different compositions of transverse modes in the output pulses. Moreover, we achieve a wide-spectrum pulsed output with a single-pulse energy of up to 116 nJ, by weakening the spectral filtering and utilizing self-cleaning. Strong spatial and spectral filtering are usually thought to be necessary for achieving STML. Our experiment verifies the necessity of spatial filtering for achieving STML, and we show that weakening unnecessary spectral filtering provides an effective way to increase the pulse energy and spectrum width of mode-locked fiber lasers. Full article

Objectives: This overview was conducted following the Preferred Reporting Items for Overviews of Reviews guidelines and aimed to collect and compare the results of systematic reviews on temporomandibular joint injection treatment. Methods: Systematic reviews of randomized clinical trials on temporomandibular disorders treated with lavage or intra-articular administrations were qualified for syntheses. The final searches were conducted on 27 February 2024, without time frame restrictions. Results: Of the 232 identified records, 42 systematic reviews were selected. The most evidence-based conclusions call into question the clinical differences between many therapeutic approaches, including the following: (1) injectable selection for the treatment of pain and hypomobility; (2) the method of performing arthrocentesis; (3) the use of imaging when rinsing the TMJ cavity; (4) the supplementation of the extracapsular administration of unprocessed blood with intracapsular deposition in the treatment of TMJ hypermobility. Conclusions: Systematic reviews based solely on randomized clinical trials proved the following differences: (1) in painful temporomandibular hypomobility, a better therapeutic effect is observed with arthrocentesis followed by I-PRF administration compared to lavage alone; (2) in painful temporomandibular hypomobility, inferior- or double-compartment injection leads to better results than superior-compartment injection; (3) in temporomandibular joint recurrent dislocation, hypertonic dextrose administration is superior to placebo, although (4) unprocessed blood has a better effect than hypertonic dextrose. PROSPERO registration number: CRD42024496142. Full article

Although the mesomorphic phase as an intermediate state has been introduced to understand polymer crystallization, the understanding of the mesomorphic phase is far from complete. Here, the effect of chain mobility on the mesophase structuring in melt-quenched poly(ʟ-lactide) (PLLA) treated in low-pressure CO₂ at 1.6–2.0 MPa and 0 °C was investigated using infrared (IR) spectroscopy, differential scanning calorimetry (DSC), and atomic force microscopy (AFM). The IR and AFM results demonstrated that the final degree of order and the kinetics of structural evolution during the CO₂-induced mesophase formation were critically dependent on the CO₂ pressure. This was attributed to the distinct dynamics of conformational evolution (gg to gt conformer transition) due to the different CO₂ pressures. The thermal behavior from the DSC results showed that CO₂ pressure dominated both the scale and dynamics of the chain motion of PLLA. At a lower CO₂ pressure of 1.6 MPa, smaller-scale segmental motion was not replaced by the larger-scale cooperative motion that occurred at a relatively higher CO₂ pressure of 2 MPa, which was favorable for faster mesophase formation. Consequently, by inhibiting direct crystallization under limited mobility conditions, it was demonstrated that varying the chain mobility controlled by CO₂ pressure and thus CO₂ solubility impacted the dynamics of the mesophase formation of PLLA. The present results have implications for understanding the role of chain mobility in determining the intermediate structural phases in semicrystalline polymers. Full article

This essay aims to defend the need to help animals in any disaster situation, be it anthropogenic, natural, or hybrid. To this end, I will first establish a brief foundation of the antispeciesist principles that have been advocated by different theorists over the last decades. Then, I will describe the conflict between environmental and animal approaches as a problem for the consideration of animals in unfavorable situations. This will be followed by the ways in which animals can be harmed in such contexts. After that, I will argue that many anthropogenic disasters affect animals, but they also deserve aid in the face of natural disasters: they are sentient beings and capable of suffering just like humans, to whom help is offered unconditionally in such cases. Finally, I will propose sentience, particularly suffering, and an ecofeminist and antispeciesist approach to address the situation of animals in disaster situations in a dialogic way between environmentalist and individual-centered positions. Full article

Small oceanic islands, such as São Miguel Island in the Azores (Portugal), face heightened susceptibility to the adverse impacts of climate change, biological invasions, and land cover changes, posing threats to biodiversity and ecosystem functions and services. Over the years, persistent conservation endeavors, notably those supported by the EU LIFE Programme since 2003, have played a pivotal role in alleviating biodiversity decline, particularly in the eastern region of São Miguel Island. This study advocates the application of remote sensing data and techniques to support the management and effective monitoring of LIFE Nature projects with land cover impacts. A land cover change detection approach utilizing Rao’s Q diversity index identified and assessed changes from 2002 to 2021 in intervention areas. The study analyzed the changes in LIFE project areas using ASTER, Landsat 8, and Sentinel 2 data through Google Earth Engine on Google Colab (with Python). This methodological approach identified and assessed land cover changes in project intervention areas within defined timelines. This technological integration enhances the potential of remote sensing for near-real-time monitoring of conservation projects, making it possible to assess their land cover impacts and intervention achievements. Full article

The combustion of diesel fuel in internal combustion engines faces challenges associated with excessive emissions of pollutants. A direct solution to this issue is the incorporation of cleaner energy sources. In this study, a numerical model was constructed to investigate the characteristics of ammonia–diesel dual-fuel application in a medium-speed diesel engine. Effects of ammonia–diesel blending ratios on engine performance and emissions were investigated. The results indicate that for this engine model, the optimal diesel energy ratio is about 22%. When the diesel energy ratio is less than 22%, the engine’s output performance is significantly affected by the diesel energy ratio, while above 22%, the influence of the intake becomes more pronounced. When the diesel energy ratio is below 16%, the cylinder cannot reach combustion conditions. Diesel energy ratios below 22% can cause ammonia leakage. With increasing diesel energy ratio, the final emissions of carbon oxides increase. With a higher diesel energy ratio, NO emissions become lower. When the diesel fuel energy ratio exceeds 22%, the N₂O emissions can be almost neglected, while below 22%, with poor combustion conditions inside the cylinder, the N₂O emissions will increase. Full article

This paper establishes a quasi-natural experiment grounded in the exogenous shock occasioned by the implementation of a compulsory corporate social responsibility (CSR) information disclosure policy. It investigates the ramifications of this mandated CSR information disclosure policy on firms’ total factor productivity (TFP) through the integration of the difference-in-differences (DID) methodology. The investigation reveals that obligatory disclosure of CSR information significantly augments firms’ total factor productivity (TFP) by mitigating agency conflicts and financial constraints. Further analysis elucidates investment efficiency and innovation enhancement as pivotal conduits through which the mandatory CSR information disclosure policy fosters firms’ TFP. The study explores the impact of mandatory CSR information disclosure on firms’ TFP mechanism, which has significant policy value and can provide useful reference for the high-standard development of China’s corporate economic transformation. Full article

Oxidative stress during in vitro of ovarian tissues has adverse effects on follicle survival. α-pinene is a monoterpenoid molecule with antioxidant activity that has great potential to maintain cell survival in vitro. This study investigated the effect of α-pinene (1.25, 2.5, 5.0, 10.0, or 20.0 μg/mL) on primordial follicle growth and morphology, as well as on stromal cells and collagen fibers in bovine ovarian slices cultured for six days. The effect of α-pinene on transcripts of catalase (CAT), superoxide dismutase (SOD), peroxiredoxin 6 (PRDX6), glutathione peroxidase (GPX1), and nuclear factor erythroid 2-related factor 2 (NRF2) was investigated by real-time PCR. The tissues were processed for histological analysis to evaluate follicular growth, morphology, stromal cell density, and collagen fibers. The results showed that 2.5, 5.0, or 10.0 µg/mL α-pinene increased the percentages of normal follicles but did not influence follicular growth. The α-pinene (10.0 µg/mL) kept the stromal cell density and collagen levels in cultured bovine ovarian tissue like uncultured tissues. Ovarian tissues cultured in control medium had reduced expression of mRNA for NRF2, SOD, CAT, GPX1, and PRDX6, but α-pinene (10.0 µg/mL) increased mRNA levels for NRF2 and PRDX6. In conclusion, 10.0 µg/mL α-pinene improves the follicular survival, preserves stromal cell density and collagen levels, and increases transcripts of NRF2 and PRDX6 after in vitro culture of bovine ovarian tissue. Full article

Surface-enhanced Raman spectroscopy (SERS) is a powerful tool for elucidating the molecular makeup of materials. It possesses the unique characteristics of single-molecule sensitivity and extremely high specificity. However, the true potential of SERS, particularly in capturing the biochemical content of particles, remains underexplored. In this study, we harnessed transformer neural networks to interpret SERS spectra, aiming to discern the amino acid profiles within proteins. By training the network on the SERS profiles of 20 amino acids of human proteins, we explore the feasibility of predicting the predominant proteins within the µL-scale detection volume of SERS. Our results highlight a consistent alignment between the model’s predictions and the protein’s known amino acid compositions, deepening our understanding of the inherent information contained within SERS spectra. For instance, the model achieved low root mean square error (RMSE) scores and minimal deviation in the prediction of amino acid compositions for proteins such as Bovine Serum Albumin (BSA), ACE2 protein, and CD63 antigen. This novel methodology offers a robust avenue not only for protein analytics but also sets a precedent for the broader realm of spectral analyses across diverse material categories. It represents a solid step forward to establishing SERS-based proteomics. Full article

Multifunctional wearable electronic sensors exhibit significant potential for applications in health management, motion tracking, intelligent healthcare, etc. In this study, we developed a novel assembly method for a polymeric silver nanowire (Ag NW)/transition metal carbide/nitride (MXene) @Loofah device using a facile solution dip-coating technique. During the pretreatment phase, the loofah was conditioned with polydiallyldimethylammonium chloride (PDAC), promoting the self-assembly of MXene layers and bolstering device stability. Then, the Ag NWs/MXene@Loofah was packaged with polyurethane to form a piezoresistive pressure sensor, which demonstrated superior pressure-sensing capabilities and was adept at registering movements of human joints and even subtle pulses. The design strategy presents a novel and rational approach to developing efficient pressure sensors. Full article

The effect of tetrasodium of 1-hydroxy ethylidene-1, 1-diphosphonic acid (HEDP·4Na) on the microstructure and phase characterization of alkali-activated fly ash–slag (AAFS) materials is not clear or well documented. In this study, XRD, DTG, TAM-air, and SEM analyses of AAFS were used to identify the microstructural changes in AAFS made with HEDP·4Na. Meanwhile, the workability and compressive strength of AAFS were evaluated. The results demonstrated that the early-age alkaline-activated reactions were retarded due to the addition of HEDP·4Na in the AAFS mixture. However, the degree of gel formation was relatively increased at a later age in the AAFS made with HEDP·4Na compared to the plain AAFS mixture. Additionally, in comparison to the control group, the incorporation of HEDP·4Na in AAFS specimens resulted in improved flowability, with increments of 5%, 15%, and 24% for concentrations of 0.1%, 0.2%, and 0.3%, respectively. The initial and final setting times were prolonged by 5% to 50%, indicating a beneficial impact on the rheological properties of the AAFS fresh mixture. Furthermore, the addition of HEDP·4Na led to an improvement in compressive strength in the AAFS mixtures, with enhancements ranging from 13% to 16% at 28 days compared to the control group. With the presence of HEDP·4Na, the increase in the degree of reactions shifted to the formation of gel phases, like C-S-H, through the combined measurement of TGA, XRD, and SEM, resulting in a denser microstructure in the AAFS matrix. This study presents novel insights into the intricate compatibility between the properties of AAFS mixtures and HEDP·4Na, facilitating a more profound comprehension of the potential improvements in the sustainable development of AAFS systems. Full article