Molecular chaperones are highly conserved across evolution and play a crucial role in preserving protein homeostasis. The 60 kDa heat shock protein (HSP60), also referred to as chaperonin 60 (Cpn60), resides within mitochondria and is involved in maintaining the organelle’s proteome integrity and homeostasis. The HSP60 family, encompassing Cpn60, plays diverse roles in cellular processes, including protein folding, cell signaling, and managing high-temperature stress. In prokaryotes, HSP60 is well understood as a GroEL/GroES complex, which forms a double-ring cavity and aids in protein folding. In eukaryotes, HSP60 is implicated in numerous biological functions, like facilitating the folding of native proteins and influencing disease and development processes. Notably, research highlights its critical involvement in sustaining oxidative stress and preserving mitochondrial integrity. HSP60 perturbation results in the loss of the mitochondria integrity and activates apoptosis. Currently, numerous clinical investigations are in progress to explore targeting HSP60 both in vivo and in vitro across various disease models. These studies aim to enhance our comprehension of disease mechanisms and potentially harness HSP60 as a therapeutic target for various conditions, including cancer, inflammatory disorders, and neurodegenerative diseases. This review delves into the diverse functions of HSP60 in regulating proteo-homeostasis, oxidative stress, ROS, apoptosis, and its implications in diseases like cancer and neurodegeneration. Full article

Accurately classifying targets and clutter plots is crucial in radar data processing. It is beneficial for filtering out a large amount of clutters and improving the track initiation speed and tracking accuracy of real targets. However, in practical applications, this problem becomes difficult due to complex electromagnetic environments such as cloud and rain clutter, sea clutter, and strong ground clutter. This has led to poor performance of some commonly used radar plot classification algorithms. In order to solve this problem and further improve classification accuracy, the radar plot classification algorithm based on evidence adaptive updating (RPC-EAU) is proposed in this paper. Firstly, the multi-dimensional recognition features of radar plots used for classification are established. Secondly, the construction and combination of mass functions based on feature sample distribution are designed. Then, a confidence network classifier containing an uncertain class was designed, and an iterative update strategy for it was provided. Finally, several experiments based on synthetic and real radar plots were presented. The results show that RPC-EAU can effectively improve the radar plot classification performance, achieving a classification accuracy of about 0.96 and a clutter removal rate of 0.95. Compared with some traditional radar pattern recognition algorithms, it can improve by 1 to 10 percentage points. The target loss rate of RPC-EAU is also the lowest, only about 0.02, which is about one third to one half of the comparison algorithms. In addition, RPC-EAU avoids clustering all radar points in each update, greatly saving the computational time. The proposed algorithm has the characteristics of high classification accuracy, low target loss rate, and less computational time. Therefore, it is suitable for radar data processing with high timeliness requirements and multiple radar plots. Full article

Background and Objectives: Worldwide, preterm birth (PTB) stands as the primary cause of mortality among children under 5 years old. Socioeconomic factors significantly impact pregnancy outcomes, influencing both maternal well-being and newborn health. Understanding and addressing these socioeconomic factors is essential for developing effective public health interventions and policies aimed at improving pregnancy outcomes. This study aims to analyse the relationship between socioeconomic factors (education level, marital status, place of residence and nationality) and PTB in Latvia, considering mother’s health habits, health status, and pregnancy process. Materials and Methods: A cross-sectional study was conducted using data from the Medical Birth Register (MBR) of Latvia about women with singleton pregnancies in 2022 (n = 15,431). Data analysis, involving crosstabs, chi-square tests, and multivariable binary logistic regression, was performed. Adjusted Odds ratios (aOR) with 95% confidence intervals (CI) were estimated. Results: Lower maternal education was statistically significantly associated with increased odds of PTB. Mothers with education levels below secondary education had over two times higher odds of PTB (aOR = 2.07, p < 0.001, CI 1.58–2.70) and those with secondary or vocational secondary education had one and a half times higher odds (aOR = 1.58, p < 0.001, CI 1.33–1.87) after adjusting for other risk factors. Study results also showed the cumulative effect of socioeconomic risk factors on PTB. Additionally, mothers facing two or three socioeconomic risk factors in Latvia exhibited one and a half times higher odds of PTB (aOR = 1.59, p = 0.021). Conclusions: The study highlights the cumulative impact of socioeconomic risk factors on PTB, with higher maternal education demonstrating the highest protective effect against it. This underscores the importance of education in promoting optimal foetal development. Since the influence of socioeconomic factors on PTB is not a widely studied issue in Latvia, further research is needed to improve understanding of this complex topic. Full article

The metabolism of glucose and lipids plays a crucial role in the normal homeostasis of the body. Although glucose is the main energy substrate, in its absence, lipid metabolism becomes the primary source of energy. The main means of fatty acid oxidation (FAO) takes place in the mitochondrial matrix through β-oxidation. Glioblastoma (GBM) is the most common form of primary malignant brain tumor (45.6%), with an incidence of 3.1 per 100,000. The metabolic changes found in GBM cells and in the surrounding microenvironment are associated with proliferation, migration, and resistance to treatment. Tumor cells show a remodeling of metabolism with the use of glycolysis at the expense of oxidative phosphorylation (OXPHOS), known as the Warburg effect. Specialized fatty acids (FAs) transporters such as FAT, FABP, or FATP from the tumor microenvironment are overexpressed in GBM and contribute to the absorption and storage of an increased amount of lipids that will provide sufficient energy used for tumor growth and invasion. This review provides an overview of the key enzymes, transporters, and main regulatory pathways of FAs and ketone bodies (KBs) in normal versus GBM cells, highlighting the need to develop new therapeutic strategies to improve treatment efficacy in patients with GBM. Full article

Though the transition from disposable to reusable surgical gowns holds substantial promise, successful implementation faces challenges. This study investigated tactile and thermophysiological comfort in surgical reusable gowns, comparing them with their disposable counterparts. Parameters such as surface roughness, compression, heat flux, and material rigidity were tested using a Fabric Touch Tester. Additionally, the water vapour permeability and static charge of the gowns were assessed. Thermophysiological comfort of the gowns was evaluated by measuring the temperature and relative humidity (RH) on test subjects during wear trials where they were engaged in an activity that mimics a surgeon’s performance. Skin temperature was monitored using iButton sensors and a thermal camera, and the impact on heart rate during the task was analysed. Following each test, participants provided subjective feedback through a questionnaire. The results indicated that reusable gowns boasted a smoother texture, translating to reduced friction on the skin and better heat transfer compared to the disposable fabrics, as indicated using FTT. They also exhibited higher water vapour permeability compared to their disposable counterparts. The wear trials revealed minimal differences in comfort between disposable and reusable gowns. While performing the activity, an increase in body temperature led to decreased RH, yet this rise did not adversely affect subject comfort, as validated using heart rate and questionnaire survey data. From a comfort point of view, switching from disposable to reusable gowns would not have drawbacks, meaning hospitals should be able to switch provided logistics and costs can be managed. Full article

Oxidative stress increases the apoptosis of intestinal epithelial cells and impairs intestinal epithelial cell renewal, which further promotes intestinal barrier dysfunction and even death. Extensive evidence supports that resveratrol and apigenin have antioxidant, anti-inflammatory, and antiproliferative properties. Here, we investigated the ability of these two compounds to alleviate diquat-induced jejunal oxidative stress and morphological injury, using the duck as a model, as well as the effects of apigenin on oxidative stress induced by H₂O₂ in immortalized duck intestinal epithelial cells (IDECs). Ducks were randomly assigned to the following four groups, with five replicates: a control (CON) group, a diquat-challenged (DIQ) group, a resveratrol (500 mg/kg) + diquat (RES) group, and an apigenin (500 mg/kg) + diquat (API) group. We found that serum catalase (CAT) activity and total antioxidant capacity (T-AOC) markedly reduced in the RES and API groups as compared to the DIQ group (p < 0.05); moreover, serum S superoxide dismutase (SOD) levels increased significantly in the API group as compared to the DIQ group (p < 0.05). In jejunal mucosa, the malondialdehyde (MDA) content in the RES and API groups decreased more than that in the DIQ group (p < 0.05). In addition, the jejunal expression levels of the NRF2 and GCLM genes in the RES and API groups increased notably compared with those in the DIQ group (p < 0.05); meanwhile, CAT activity in the RES and API groups was markedly elevated compared with that in the CON group (p < 0.05). In IDECs, apigenin significantly restrained the H₂O₂-mediated increase in MDA content and decrease in CAT levels (p < 0.05). Furthermore, apigenin increased the protein expression of p-NRF2, NRF2, p-AKT, and p-P38; downregulated that of cleaved caspase-3 and cleaved caspase-9; and reduced the ratio of Bax/Bcl-2 in H₂O₂-treated IDECs (p < 0.05). In conclusion, resveratrol and apigenin can be used as natural feed additives to protect against jejunal oxidative stress in ducks. Full article

Faced with the urgent challenge of global warming, green bonds play an important role in promoting economic transformation and improving environmental quality by financing environmentally friendly projects. However, the actual effects of green bonds, especially their impact on corporate environmental performance, and the mechanisms behind it, still need to be studied and validated. Based on the time-varying difference-in-differences (DID) model, this study uses 85 Chinese A-share listed companies that have issued green bonds from 2013 to 2022, to study the impact of green bond issuance on corporate environmental performance and the potential mechanisms. The results show that green bonds issuance effectively promotes the improvement of corporate environmental performance; this promotion is more significant for labor-intensive enterprises, larger enterprises, and enterprises with more government subsidies. In terms of the influencing mechanism, R&D investment and green innovation play partial mediating roles, media attention and analyst attention play positive moderating roles. This study further validates and complements the signal theory of green bonds and makes relevant suggestions for the development of green bonds in China. Full article

Progesterone (PROG) and estrone (E₁) are typical reproductive hormones in dairy cows. Assessing the levels of these hormones in vivo can aid in estrus identification. In the present work, the feasibility of the qualitative and quantitative detection of PROG and E₁ using terahertz time-domain spectroscopy (THz-TDS) and metamaterial technology was preliminarily investigated. First, the time domain spectra, frequency domain spectra, and absorption coefficients of PROG and E₁ samples were collected and analyzed. A vibration analysis was conducted using density functional theory (DFT). Subsequently, a double-ring (DR) metamaterial structure was designed and simulated using the frequency domain solution algorithm in CST Studio Suite (CST) software. This aimed to ensure that the double resonance peaks of DR were similar to the absorption peaks of PROG and E₁. Finally, the response of DR to different concentrations of PROG/E₁ was analyzed and quantitatively modeled. The results show that a qualitative analysis can be conducted by comparing the corresponding DR resonance peak changes in PROG and E₁ samples at various concentrations. The best R² for the PROG quantitative model was 0.9872, while for E₁, it was 0.9828. This indicates that terahertz spectral–metamaterial technology for the qualitative and quantitative detection of the typical reproductive hormones PROG and E₁ in dairy cows is feasible and worthy of in-depth exploration. This study provides a reference for the identification of dairy cow estrus. Full article

Unhealthy lifestyles (high-fat diet, smoking, alcohol consumption, too little exercise, etc.) in the current society are prone to cause lipid metabolism disorders affecting the health of the organism and inducing the occurrence of diseases. Saponins, as biologically active substances present in plants, have lipid-lowering, inflammation-reducing, and anti-atherosclerotic effects. Saponins are thought to be involved in the regulation of lipid metabolism in the body; it suppresses the appetite and, thus, reduces energy intake by modulating pro-opiomelanocortin/Cocaine amphetamine regulated transcript (POMC/CART) neurons and neuropeptide Y/agouti-related peptide (NPY/AGRP) neurons in the hypothalamus, the appetite control center. Saponins directly activate the AMP-activated protein kinase (AMPK) signaling pathway and related transcriptional regulators such as peroxisome-proliferator-activated-receptors (PPAR), CCAAT/enhancer-binding proteins (C/EBP), and sterol-regulatory element binding proteins (SREBP) increase fatty acid oxidation and inhibit lipid synthesis. It also modulates gut–liver interactions to improve lipid metabolism by regulating gut microbes and their metabolites and derivatives—short-chain fatty acids (SCFAs), bile acids (BAs), trimethylamine (TMA), lipopolysaccharide (LPS), et al. This paper reviews the positive effects of different saponins on lipid metabolism disorders, suggesting that the gut–liver axis plays a crucial role in improving lipid metabolism processes and may be used as a therapeutic target to provide new strategies for treating lipid metabolism disorders. Full article

In the realm of conditionally automated driving, understanding the crucial transition phase after a takeover is paramount. This study delves into the concept of post-takeover stabilization by analyzing data recorded in two driving simulator experiments. By analyzing both driving and physiological signals, we investigate the time required for the driver to regain full control and adapt to the dynamic driving task following automation. Our findings show that the stabilization time varies between measured parameters. While the drivers achieved driving-related stabilization (winding, speed) in eight to ten seconds, physiological parameters (heart rate, phasic skin conductance) exhibited a prolonged response. By elucidating the temporal and cognitive dynamics underlying the stabilization process, our results pave the way for the development of more effective and user-friendly automated driving systems, ultimately enhancing safety and driving experience on the roads. Full article

In this work, a novel approach involving coating fine PEEK powder on prepreg is introduced to improve wedge peel strength and reduce interlaminar voids. CF/PEEK laminates with resin interleaving are in situ consolidated by laser-assisted fiber placement. The morphology of the powdered surface is obtained using an optical profilometer, and the surface roughness and volume of added resin are calculated accordingly. Interface and surface temperature are measured during the layup process. Thermal history indicates that very short bonding time is the dominating factor for voids and limited interlayer strength. Laminate porosity and microscopic features are characterized with an optical microscope. The porosity of resin-interleaved laminates decreases to 3.7%, while the resin content only increases by 4.5% in the meantime. This is because interlayer resin particles rapidly melt under laser heating and quickly fill the voids between layers. The wedge peel strength of resin-interleaved laminates can increase by 30.1% without a repass treatment. This could be attributed to the increase in resin intimate contact and reduction in interlayer voids. Full article

The influence of spatial resolution on classification accuracy strongly depends on the research object. With regard to unmanned aerial vehicle (UAV)-based weed mapping, contradictory results on the influence of spatial resolution have been attained so far. Thus, this study evaluates the effect of spatial resolution on the classification accuracy of weeds in a soybean field located in Belm, Lower Saxony, Germany. RGB imagery of four spatial resolutions (0.27, 0.55, 1.10, and 2.19 cm ground sampling distance) corresponding to flight altitudes of 10, 20, 40, and 80 m were assessed. Multinomial logistic regression was used to classify the study area, using both pixel- and object-based approaches. Additionally, the flight and processing times were monitored. For the purpose of an accuracy assessment, the producer’s, user’s, and overall accuracies as well as the F1 scores were computed and analyzed for statistical significance. Furthermore, McNemar’s test was conducted to ascertain whether statistically significant differences existed between the classifications. A linear relationship between resolution and accuracy was found, with a diminishing accuracy as the resolution decreased. Pixel-based classification outperformed object-based classification across all the resolutions examined, with statistical significance (p < 0.05) for 10 and 20 m. The overall accuracies of the pixel-based approach ranged from 80 to 93 percent, while the accuracies of the object-based approach ranged from 75 to 87 percent. The most substantial drops in the weed-detection accuracy with regard to altitude occurred between 20 and 40 m for the pixel-based approach and between 10 and 20 m for the object-based approach. While the decline in accuracy was roughly linear as the flight altitude increased, the decrease in the total time required was exponential, providing guidance for the planning of future UAV-based weed-mapping missions. Full article

Investigating the factors that influence individual decisions to participate in social health insurance is an essential component of constructing a multi-tiered, comprehensive social health insurance system, and religious beliefs may constitute an important potential factor. Utilising data from the China General Social Survey (CGSS), this study has developed a comprehensive explanatory framework encompassing both macro- and micro-level analyses to ascertain the impact of religious beliefs on individual decisions to participate in social health insurance through quantitative methods. The findings indicate that religious beliefs significantly diminish the likelihood of individuals participating in social health insurance, and the influence varies among different types of religions; endogeneity and robustness tests offer robust support for these conclusions. With respect to heterogeneity, the influence of religious beliefs on the decision to participate in social health insurance exhibits differentiation across dimensions such as educational attainment, social trust levels, income levels, and self-rated health statuses. Furthermore, the social interaction effect and the employment opportunity effect are identified as potential mechanisms driving this influence. Full article

Cellular demise is a pivotal event in both developmental processes and disease states, with mitochondrial regulation playing an essential role. Traditionally, cell death was categorized into distinct types, considered to be linear and mutually exclusive pathways. However, the current understanding has evolved to recognize the complex and interconnected mechanisms of cell death, especially within apoptosis, pyroptosis, and necroptosis. Apoptosis, pyroptosis, and necroptosis are governed by intricate molecular pathways, with mitochondria acting as central decision-makers in steering cells towards either apoptosis or pyroptosis through various mediators. The choice between apoptosis and necroptosis is often determined by mitochondrial signaling and is orchestrated by specific proteins. The molecular dialogue and the regulatory influence of mitochondria within these cell death pathways are critical research areas. Comprehending the shared elements and the interplay between these death modalities is crucial for unraveling the complexities of cellular demise. Full article

Glutamic acid decarboxylase antibody (GADAb) has emerged as a significant biomarker for clinical diagnosis and prognosis in type 1 diabetes (T1D). In this study, we investigated the potential utilization of glass capillary solid-state nanopores as a cost-effective and easily preparable platform for the detection of individual antigens, antibodies, and antigen-antibody complexes without necessitating any modifications to the nanopores. Our findings revealed notable characteristic variations in the translocation events of glutamic acid decarboxylase (GAD65) through nanopores under different voltage conditions, discovered that anomalous phenomenon of protein translocation events increasing with voltage may potentially be caused by the crowding of multiple proteins in the nanopores, and demonstrated that there are multiple components in the polyclonal antibodies (GADAb-poly). Furthermore, we achieved successful differentiation between GAD65, GADAb, and GADAb-GAD65 complexes. These results offer promising prospects for the development of a rapid and reliable GADAb detection method, which holds the potential to be applied in patient serum samples, thereby facilitating a label-free, cost-effective, and early diagnosis of type I diabetes. Full article

Enhancing yield and achieving environmental goals represent challenges for the future of agriculture. Rational nitrogen (N) management is one of the most promising ways to meet this challenge. However, complicated nitrogen management strategies and considerable input requirements still exist in rice–ratoon rice production. To address this issue, field experiments were conducted with two main high-yield rice crop genotypes and five fertilization treatments at six sites in Southwest China from 2018 to 2020. The results showed the following: (1) the yield of the main rice crop was extremely significantly affected by the year, location, and fertilization, but not by genotype; (2) the yield of the ratoon rice was extremely significantly affected by year, genotype, location, and fertilization; and (3) the total plant N content (TPN) and leaf SPAD value at the full heading stage of the main crop were significantly positively correlated with the total soil N content (TSN) and soil available N (SAN) content of the basic soil. The highly efficient N application rate of grain- and bud-promoting fertilizer for ratoon rice was 60–120 kg ha⁻¹. The TSN, SAN, TPN, and SPAD values higher than 0.247 kg N kg⁻¹, 298 mg N kg⁻¹, 2.159 kg N kg⁻¹, and 49.94 were, respectively, considered the reference values when not applying grain- and bud-promoting fertilizer. A regression equation was established to predict the amount of high-efficiency grain- and bud-promoting fertilizer based on the TSN and SPAD. Overall, the yield of rice–ratoon rice was significantly affected by year, genotype, location, fertilization, and their interactions. The use of the predicted grain- and bud-promoting fertilizer regression equation can achieve high yields under simplified and reduced N input practices in the rice–ratoon rice systems. Full article

Lysine acetyltransferase 8, also known as KAT8, is an enzyme involved in epigenetic regulation, primarily recognized for its ability to modulate histone acetylation. This review presents an overview of KAT8, emphasizing its biological functions, which impact many cellular processes and range from chromatin remodeling to genetic and epigenetic regulation. In many model systems, KAT8’s acetylation of histone H4 lysine 16 (H4K16) is critical for chromatin structure modification, which influences gene expression, cell proliferation, differentiation, and apoptosis. Furthermore, this review summarizes the observed genetic variability within the KAT8 gene, underscoring the implications of various single nucleotide polymorphisms (SNPs) that affect its functional efficacy and are linked to diverse phenotypic outcomes, ranging from metabolic traits to neurological disorders. Advanced insights into the structural biology of KAT8 reveal its interaction with multiprotein assemblies, such as the male-specific lethal (MSL) and non-specific lethal (NSL) complexes, which regulate a wide range of transcriptional activities and developmental functions. Additionally, this review focuses on KAT8’s roles in cellular homeostasis, stem cell identity, DNA damage repair, and immune response, highlighting its potential as a therapeutic target. The implications of KAT8 in health and disease, as evidenced by recent studies, affirm its importance in cellular physiology and human pathology. Full article

Bartonella henselae is a Gram-negative bacterium causing a variety of clinical symptoms, ranging from cat-scratch disease to severe systemic infections, and it is primarily transmitted by infected fleas. Its status as an emerging zoonotic pathogen and its capacity to persist within host erythrocytes and endothelial cells emphasize its clinical significance. Despite progress in understanding its pathogenesis, limited knowledge exists about the virulence factors and regulatory mechanisms specific to the B. henselae strain Houston-1. Exploring these aspects is crucial for targeted therapeutic strategies against this versatile pathogen. Using reverse-vaccinology-based subtractive proteomics, this research aimed to identify the most antigenic proteins for formulating a multi-epitope vaccine against the B. henselae strain Houston-1. One crucial virulent and antigenic protein, the PAS domain-containing sensor histidine kinase protein, was identified. Subsequently, the identification of B-cell and T-cell epitopes for the specified protein was carried out and the evaluated epitopes were checked for their antigenicity, allergenicity, solubility, MHC binding capability, and toxicity. The filtered epitopes were merged using linkers and an adjuvant to create a multi-epitope vaccine construct. The structure was then refined, with 92.3% of amino acids falling within the allowed regions. Docking of the human receptor (TLR4) with the vaccine construct was performed and demonstrated a binding energy of −1047.2 Kcal/mol with more interactions. Molecular dynamic simulations confirmed the stability of this docked complex, emphasizing the conformation and interactions between the molecules. Further experimental validation is necessary to evaluate its effectiveness against B. henselae. Full article

A novel station-keeping strategy leveraging periodic revolutions of homeomorphic orbits in the Elliptic Restricted Three-Body Problem within the pulsating frame is presented. A systemic approach founded on arc-length continuation is presented for the discovery, computation, and classification of periodic revolutions that morph from their traditional circular restricted three-body counterparts to build an a priori dataset. The dataset is comprehensive in covering all possible geometric architectures of the restricted problem. Shape similarity is quantified using Hausdorff distance and works as a filter for the station-keeping algorithm in relation to appropriate target conditions. Finally, an efficient scheme to quantify impulsive orbit maintenance maneuvers that minimize the total fuel cost is presented. The proposed approach is salient in its generic applicability across any elliptic three-body system and any periodic orbit family. Finally, average annual station-keeping costs using the described methodology are quantified for selected “orbits of interest” in the cis-lunar and the Sun–Earth systems. The robustness and efficacy of the approach instill confidence in its applicability for realistic mission design scenarios. Full article

In Yaoundé, Cameroon, where walking dominates transport modes, pedestrian safety remains an issue as pedestrians account for a fair share of road traffic casualties, partly due to the lack of walking policies and pedestrian facilities safety data, hindering targeted intervention. This study used a pedestrian safety index (PSI) and the Global Walkability Index (GWI) to investigate 12 road segments frequented by diverse pedestrian groups. Indexes were graded from E—lowest to A—highest and analyzed using description and rank correlation. Main safety issues included lack of adequate and accessible sidewalks, bollards, pedestrian crossings, signage, shade, and street lighting. Only one segment (R7) achieved grade C, while the remainder scored D or E, indicating poor pedestrian safety conditions and an unpleasant walking experience. The correlation coefficient (0.69) between the PSI and GWI at a 99% significance level validated the safety assessment, providing confidence in the results. A seven-year (2024–2030) safety strategy is proposed to improve all roads to grade B. This strategy contains several interventions, including engineering improvement, which have been proven effective. This study offers evidence for city officials to improve pedestrian safety and informs walking policies and the implementation of upcoming projects. Future research should quantify the recommendations’ benefits and validate indexes with crash or conflict data. Full article

Sepsis is a life-threatening syndrome triggered by infection and accompanied by high mortality, with antimicrobial resistances (AMRs) further escalating clinical challenges. The rapid and reliable detection of causative pathogens and AMRs are key factors for fast and appropriate treatment, in order to improve outcomes in septic patients. However, current sepsis diagnostics based on blood culture is limited by low sensitivity and specificity while current molecular approaches fail to enter clinical routine. Therefore, we developed a suppression PCR-based selective enrichment sequencing approach (SUPSETS), providing a molecular method combining multiplex suppression PCR with Nanopore sequencing to identify most common sepsis-causative pathogens and AMRs using plasma cell-free DNA. Applying only 1 mL of plasma, we targeted eight pathogens across three kingdoms and ten AMRs in a proof-of-concept study. SUPSETS was successfully tested in an experimental research study on the first ten clinical samples and revealed comparable results to clinical metagenomics while clearly outperforming blood culture. Several clinically relevant AMRs could be additionally detected. Furthermore, SUPSETS provided first pathogen and AMR-specific sequencing reads within minutes of starting sequencing, thereby potentially decreasing time-to-results to 11–13 h and suggesting diagnostic potential in sepsis. Full article

Innovations in cancer immunotherapy have resulted in the development of several novel immunotherapeutic strategies that can disrupt immunosuppression. One key advancement lies in immune checkpoint inhibitors (ICIs), which have shown significant clinical efficacy and increased survival rates in patients with various therapy-resistant cancers. This immune intervention consists of monoclonal antibodies directed against inhibitory receptors (e.g., PD-1) on cytotoxic CD8 T cells or against corresponding ligands (e.g., PD-L1/PD-L2) overexpressed on cancer cells and other cells in the tumor microenvironment (TME). However, not all cancer cells respond—there are still poor clinical responses, immune-related adverse effects, adaptive resistance, and vulnerability to ICIs in a subset of patients with cancer. This challenge showcases the heterogeneity of cancer, emphasizing the existence of additional immunoregulatory mechanisms in many patients. Therefore, it is essential to investigate PD-L1’s interaction with other oncogenic genes and pathways to further advance targeted therapies and address resistance mechanisms. Accordingly, our aim was to investigate the mechanisms governing PD-L1 expression in tumor cells, given its correlation with immune evasion, to uncover novel mechanisms for decreasing PD-L1 expression and restoring anti-tumor immune responses. Numerous studies have demonstrated that the upregulation of Raf Kinase Inhibitor Protein (RKIP) in many cancers contributes to the suppression of key hyperactive pathways observed in malignant cells, alongside its broadening involvement in immune responses and the modulation of the TME. We, therefore, hypothesized that the role of PD-L1 in cancer immune surveillance may be inversely correlated with the low expression level of the tumor suppressor Raf Kinase Inhibitor Protein (RKIP) expression in cancer cells. This hypothesis was investigated and we found several signaling cross-talk pathways between the regulations of both RKIP and PD-L1 expressions. These pathways and regulatory factors include the MAPK and JAK/STAT pathways, GSK3β, cytokines IFN-γ and IL-1β, Sox2, and transcription factors YY1 and NFκB. The pathways that upregulated PD-L1 were inhibitory for RKIP expression and vice versa. Bioinformatic analyses in various human cancers demonstrated the inverse relationship between PD-L1 and RKIP expressions and their prognostic roles. Therefore, we suspect that the direct upregulation of RKIP and/or the use of targeted RKIP inducers in combination with ICIs could result in a more targeted anti-tumor immune response—addressing the therapeutic challenges related to PD-1/PD-L1 monotherapy alone. Full article