Collagen-rich liver-derived extracellular matrix hydrogels augment survival and function of primary rat liver sinusoidal endothelial cells and hepatocytes.

Liver sinusoidal endothelial cells (LSECs) are key targets for addressing metabolic dysfunction-associated steatotic liver disease (MASLD). However, isolating and culturing primary LSECs is challenging due to rapid dedifferentiation, resulting in loss of function. The extracellular matrix (ECM) likely plays a crucial role in maintaining the fate and function of LSECs. In this study, we explored the influence of liver-ECM (L-ECM) on liver cells and developed culture conditions that maintain the differentiated function of liver cells in vitro for prolonged periods. Porcine liver-derived L-ECM, containing 34.9 % protein, 0.045 % glycosaminoglycans, and negligible residual DNA (41.2 ng/mg), was utilized to culture primary rat liver cells in generated hydrogels. Proteomic analyses and molecular weight distribution of proteins of solubilized L-ECM revealed the typical diverse ECM core matrisome, with abundant collagens. L-ECM hydrogels showed suitable stiffness and stress relaxation properties. Furthermore, we demonstrated that collagen-rich L-ECM hydrogels enhanced LSECs' and hepatocytes' viability, and reduced the dedifferentiation rate of LSECs. In addition, hepatocyte function was maintained longer by culture on L-ECM hydrogels compared to traditional culturing. These beneficial effects are likely attributed to the bioactive macromolecules including collagens, and mechanical and microarchitectural properties of the L-ECM hydrogels.

ß-glucan: a potent adjuvant in immunotherapy for digestive tract tumors.

The immunotherapy for gastrointestinal tumors, as a significant research direction in the field of oncology treatment in recent years, has garnered extensive attention due to its potential therapeutic efficacy and promising clinical application prospects. Recent advances in immunotherapy notwithstanding, challenges persist, such as side effects, the complexity of the tumor immune microenvironment, variable patient responses, and drug resistance. Consequently, there is a pressing need to explore novel adjunctive therapeutic modalities. ß-glucan, an immunomodulatory agent, has exhibited promising anti-tumor efficacy in preclinical studies involving colorectal cancer, pancreatic cancer, and gastric cancer, while also mitigating the adverse reactions associated with chemotherapy and enhancing patients' quality of life. However, further clinical and fundamental research is warranted to comprehensively evaluate its therapeutic potential and underlying biological mechanisms. In the future, ß-glucan holds promise as an adjunctive treatment for gastrointestinal tumors, potentially bringing significant benefits to patients.

Experimental study on axial tensile properties of basalt fibre reinforced recycled aggregate concrete.

In order to investigate the tensile properties of basalt fibre reinforced recycled aggregate concrete (BFRAC), the axial tensile tests were carried out on BFRAC specimens using the concrete axial tensile testing device. The effects of basalt fibre (BF) content and recycled aggregate replacement rate on the tensile properties of BFRAC were quantitatively investigated, and the tensile damage mechanism of BFRAC was analysed. The following conclusions were drawn: The volume fraction of BF had the most prominent effect on the axial tensile properties of BFRAC. The axial tensile strength and peak tensile strain of BFRAC both showed the change rule of first increasing and then decreasing with the increase of BF volume fraction. The replacement rate of recycled aggregate is negatively correlated with the tensile properties of BFRAC. The larger the replacement rate, the worse the tensile properties of BFRAC. When the replacement rate of recycled aggregate is 30 % and the volume fraction of BF is 0.3 %, the tensile properties of BFRAC are better, as well as its economic and environmental performance. The axial tensile strength and peak tensile strain were 2.08 MPa and 114 × 10-6, respectively. BFRAC exhibits the toughening and crack arresting effect of BF, and the crack development is relatively slow, showing more obvious plastic damage characteristics.

Mendelian randomization demonstrates a causal link between peripheral circulating acylcarnitines and intracranial aneurysms.

Intracranial aneurysm (IA) is the most prevalent type of cerebral vascular disease causing life-threatening subarachnoid hemorrhages (SAH). A long-term vascular structure remodeling is considered as the main pathophysiological feature of IAs. However, the causal factors triggering the pathophysiological process are not clear. Recently, the abnormalities of peripheral circulating proteins and metabolites have been found in IAs patients and associated with the ruptures. We comprehensively investigated the potential causal relationship between blood metabolites and proteins and IAs using the mendelian randomization (MR) analysis. We applied two-sample MR to explore the potential causal association between peripheral circulating metabolites (191 blood metabolites) and proteins (1398 proteins) and IAs using data from the FinnGen study and the GWAS datasets published by Bakker et al. We identified palmitoylcarnitine, stearoylcarnitine and 2-tetradecenoylcarnitine as causal contributors of IAs and ruptures. Further two-step mediation MR analysis suggested that hypertension as one of the contributors of IAs and ruptures mediated the causal relationship between palmitoylcarnitine, stearoylcarnitine and 2-tetradecenoylcarnitine and IAs. Together, our study demonstrates that blood metabolic palmitoylcarnitine, stearoylcarnitine and 2-tetradecenoylcarnitine are causally linked to the formation and rupture of IAs. Hypertension partially mediates the causal effects.

IL-17B alleviates the pathogenesis of systemic lupus erythematosus by inhibiting FASN-mediated differentiation of B cells.

The interleukin-17 (IL-17) family of cytokines has emerged as a critical player in autoimmune disease, including systemic lupus erythematosus (SLE). However, the role of IL-17B, a poorly understood cytokine, in the pathogenesis of SLE is still not clear. In this study, we investigated the role of IL-17B in the activation and differentiation of B cells, and the pathogenesis of SLE. Intriguingly, IL-17B deficiency aggravated disease in lupus-prone mice and promoted the activation of B cells and the differentiation of germinal center (GC) B cells and plasma cells, while recombinant mouse IL-17B (rmIL-17B) significantly alleviated disease in lupus-prone mice. Mechanistically, rmIL-17B inhibited the activation of the Toll-like receptor (TLR) and interferon (IFN) pathways in B cells by downregulating the FASN-mediated lipid metabolism. Loss of FASN significantly alleviated the disease in lupus-prone mice and inhibited the activation and differentiation of B cells. In addition, B cells had greater FASN expression and lower IL-17RB levels in patients with SLE than in healthy controls. Our study described the role of IL-17B in regulating B-cell activation and differentiation, and alleviating the onset of SLE. These findings will lay a theoretical foundation for further understanding of the pathogenesis of SLE.

Relationship between cognitive function and sleep quality in middle-aged and older adults for minimizing disparities and achieving equity in health: Evidence from multiple nationwide cohorts.

BACKGROUND: Cognitive decline, a heavy burden on middle-aged and older adults as global aging is aggravated, was found to be associated with sleep quality. However, the country-between heterogeneity of the association prevented us from quantifying underlying relationship and identifying potential effect modifiers for vulnerable populations and targeted interventions. METHODS: We collected data from 79,922 eligible adults in five nationwide cohorts, examined the respective relationships between cognitive function and sleep quality, synthesized underlying average relationships by meta-analysis, and explored effect modifiers by meta-regressions. Additionally, we conducted subgroup and interaction analyses to identify vulnerable populations and to determine their disparities in vulnerability. RESULTS: Although country-between disparities exist, cognitive function is robustly associated with sleep quality in middle-aged and older adults worldwide, with an effect (ß) of 0.015 [0.003, 0.027]. Executive function is the subdomain most relevant to sleep quality. Disparities in the effects of sleep quality on subdomains exist in populations with different sexes (orientation: ßfemale/ßmale = 1.615, P = 0.020), marital statuses (orientation: ßunmarried/ßmarried = 2.074, P < 0.001), education levels (orientation:ßuneducated/ßeducated = 2.074, P < 0.001) and chronic disease statuses (memory: ßunhealthy/ßhealthy = 1.560, P = 0.005). CONCLUSIONS: Cognitive function decreases with worsening sleep quality in middle-aged and older adults. Vulnerability to poor sleep generally persists in singles, females, the uneducated and people with chronic diseases. To minimize disparities and achieve health equity, we advocate for targeted interventions, i.e., encouraging socialization in singles, confirming effectiveness of hormone replacement therapy in females, employing compulsory education in middle-aged and older adults.

SelK promotes glioblastoma cell proliferation by inhibiting ß-TrCP1 mediated ubiquitin-dependent degradation of CDK4.

BACKGROUND: Glioblastoma (GB) is recognized as one of the most aggressive brain tumors, with a median survival of 14.6 months. However, there are still some patients whose survival time was greater than 3 years, and the biological reasons behind this clinical phenomenon arouse our research interests. By conducting proteomic analysis on tumor tissues obtained from GB patients who survived over 3 years compared to those who survived less than 1 year, we identified a significant upregulation of SelK in patients with shorter survival times. Therefore, we hypothesized that SelK may be an important indicator related to the occurrence and progression of GBM. METHODS: Proteomics and immunohistochemistry from GB patients were analyzed to investigate the correlation between SelK and clinical prognosis. Cellular phenotypes were evaluated by cell cycle analysis, cell viability assays, and xenograft models. Immunoblots and co-immunoprecipitation were conducted to verify SelK-mediated ubiquitin-dependent degradation of CDK4. RESULTS: SelK was found to be significantly upregulated in GB samples from short-term survivors (≤ 1 year) compared to those from long-term survivors (≥ 3 years), and its expression levels were negatively correlated with clinical prognosis. Knocking down of SelK expression reduced GB cell viability, induced G0/G1 phase arrest, and impaired the growth of transplanted glioma cells in nude mice. Down-regulation of SelK-induced ER stress leads to a reduction in the expression of SKP2 and an up-regulation of ß-TrCP1 expression. Up-regulation of ß-TrCP1, thereby accelerating the ubiquitin-dependent degradation of CDK4 and ultimately inhibiting the malignant proliferation of the GB cells. CONCLUSION: This study discovered a significant increase in SelK expression in GB patients with poor prognosis, revealing a negative correlation between SelK expression and patient outcomes. Further mechanistic investigations revealed that SelK enhances the proliferation of GB cells by targeting the endoplasmic reticulum stress/SKP2/ß-TrCP1/CDK4 axis.

Single-cell transcriptomic analysis of immune cell dynamics in the healthy human endometrium.

The microenvironment of the endometrial immune system is crucial to the success of placental implantation and healthy pregnancy. However, the functionalities of immune cells across various stages of the reproductive cycle have yet to be fully comprehended. To address this, we conducted advanced bioinformatic analysis on 230,049 high-quality single-cell transcriptomes from healthy endometrial samples obtained during the proliferative, secretory, early pregnancy, and late pregnancy stages. Our investigation has unveiled that proliferative natural killer (NK) cells, a potential source of endometrial NK cells, exhibit the most robust proliferative and differentiation potential during non-pregnant stages. We have also identified similar differentiation trajectories of NK cells originating from proliferative NK cells across four stages. Notably, during early pregnancy, NK cells demonstrate the highest oxidative phosphorylation metabolism activity, and, in conjunction with macrophages and T cells, exhibit the strongest type II interferon response. With spatial transcriptome data, we have discerned that the most robust immune-non-immune interactions are associated with the promotion and inhibition of cell proliferation, differentiation and migration during four stages. Furthermore, we have compiled lists of stage-specific risk genes implicated in reproductive diseases, which hold promise as potential disease biomarkers. Our study provides insights into the dynamics of the endometrial immune microenvironment during different reproductive cycle stages, thus serving as a reference for detecting pathological changes during pregnancy.

Association between depressive duration and cognitive decline in middle-aged and older adults: Evidence from the Health and Retirement Study 2010-2018.

BACKGROUND: Depression has been found to be associated with cognitive decline, but whether longer depressive durations lead to more severe cognitive declines has not been investigated. We aimed to estimate the association between depressive duration and cognitive decline in middle-aged and older Americans based on a large-scale representative population study. METHODS: We included 27,886 participants from the Health and Retirement Study (HRS) in 2010-2018. Four datasets with 2-, 4-, 6-, and 8-year consecutive interviews were further derived which involving persistent depressed and persistent depression-free individuals. Multiple linear regressions were constructed to estimate the effects of each depressive duration on the decline in global cognition, memory and mental status. Meta-regressions were performed to test the linear trends and to explore the heterogeneity between sex, age and baseline cognitive function along with subgroup analyses. RESULTS: Depressive durations of 2, 4, 6, and 8 years were associated with reductions in global cognitive scores of 0.62 points (95% CI: 0.51-0.73), 0.77 points (95% CI: 0.60-0.94), 0.83 points (95% CI: 0.55-1.10), and 1.09 points (95% CI: 0.63-1.55), respectively, indicating a linear trend (P = 0.016). More pronounced associations were observed in middle-aged adults and females. Similar patterns were found in the associations between depressive duration and two subdomains, i.e., memory and mental health. LIMITATIONS: This study is essentially a cross-sectional study and therefore cannot provide causal associations. CONCLUSIONS: Longer depressive durations were linearly related to more severe cognitive declines. Timely intervention for depression targeted middle-aged adults can more effectively alleviate cognition-related burdens.

Factors influencing the survival status of the hip joint in post-collapse femoral head necrosis.

BACKGROUND: Despite hip function typically deteriorating in the post-collapse stage of osteonecrosis of the femoral head (ONFH), some patients can still demonstrate long-term favorable hip function, a state termed "survival with collapse". This study aims to identify the characteristics of patients suitable for "survival with collapse" in cases of ONFH. METHODS: This cross-sectional study included 65 patients (87 hips) diagnosed with post-collapse ONFH for ≥ 3 years (average 9.1 years, range 3-23 years). Hip function was assessed using the Harris Hip Score (HHS). Demographic, clinical, and radiographic data were compared between the favorable group (HHS > 80) and the poor group (HHS ≤ 80). Independent protective factors for hip function were identified by multivariate analysis and receiver operating characteristic (ROC) curve analysis was further applied to evaluate these factors' diagnostic efficacy. RESULTS: The favorable and poor groups included 46 and 41 hips, respectively. Significant differences were found in body mass index (BMI), Association Research Circulation Osseous (ARCO) stage, collapse degree, Japanese Investigation Committee (JIC) classification, necrotic size, and hip subluxation between the two groups (p < 0.05). Multivariate logistic regression identified collapse < 3 mm(OR:14.49, 95%CI: 3.52-59.68, p < 0.001), JIC types B (OR: 11.08, 95% CI: 1.07-115.12, p < 0.05) and C1(OR: 5.18, 95% CI: 1.47-18.20, p < 0.05) as independent protective factors for hip function, while BMI (OR: 0.76, 95% CI: 0.59-0.97, p = 0.029) was an independent risk factor. ROC curve analysis demonstrated that both collapse degree (AUC = 0.798, sensitivity = 91.3%, specificity = 68.3%, p < 0.0001) and JIC classification (AUC = 0.787, sensitivity = 80.4%, specificity = 73.2%, p < 0.0001) had satisfactory diagnostic value for hip function. Combining JIC classification and collapse degree (AUC = 0.868, sensitivity = 76.1%, specificity = 85.4%, p < 0.0001) significantly enhanced diagnostic efficacy compared to using either alone (p < 0.05). CONCLUSION: In ONFH, femoral head collapse does not necessarily determine a poor prognosis. Patients with mild collapse (< 3 mm) and preserved anterolateral wall are more likely to retain satisfactory hip function, making them candidates for "survival with collapse."

Sparse reconstruction of sound field using pattern-coupled Bayesian compressive sensing.

Conventional near-field acoustic holography based on compressive sensing either does not fully exploit the underlying block-sparse structures of the signal or suffers from a mismatch between the actual and predefined block structure due to the lack of prior information about block partitions, resulting in poor accuracy in sound field reconstruction. In this paper, a pattern-coupled Bayesian compressive sensing method is proposed for sparse reconstruction of sound fields. The proposed method establishes a hierarchical Gaussian-Gamma probability model with a pattern-coupled prior based on the equivalent source method, transforming the sound field reconstruction problem into recovering the sparse coefficient vector of the equivalent source strengths within the compressive sensing framework. A set of hyperparameters is introduced to control the sparsity of each element in the sparse coefficient vector of the equivalent source strengths, where the sparsity of each element is determined by both its own hyperparameters and those of its immediate neighbors. This approach enables the promotion of block sparse solutions and achieves better performance in solving for the sparse coefficient vector of the equivalent source strengths without prior information of block partitions. The effectiveness and superiority of the proposed method in reconstructing sound fields are verified by simulations and experiments.

Optimal dosage ranges of various exercise types for enhancing timed up and go performance in Parkinson's disease patients: a systematic review and Bayesian network meta-analysis.

Objective: To examine the dose-response relationship between specific types of exercise for alleviating Timed up and Go (TUG) in Parkinson's disease PD. Design: Systematic review and Bayesian network meta-analysis. Data sources: PubMed, Medline, Embase, PsycINFO, Cochrane Library, and Web of Science were searched from inception until February 5th, 2024. Study analysis: Data analysis was conducted using R software with the MBNMA package. Effect sizes of outcome indicators were expressed as mean deviation (MD) and 95% confidence intervals (95% CrI). The risk of bias in the network was evaluated independently by two reviewers using ROB2. Results: A total of 73 studies involving 3,354 PD patients. The text discusses dose-response relationships in improving TUG performance among PD patients across various exercise types. Notably, Aquatic (AQE), Mix Exercise (Mul_C), Sensory Exercise (SE), and Resistance Training (RT) demonstrate effective dose ranges, with AQE optimal at 1500 METs-min/week (MD: -8.359, 95% CI: -1.398 to -2.648), Mul_C at 1000 METs-min/week (MD: -4.551, 95% CI: -8.083 to -0.946), SE at 1200 METs-min/week (MD: -5.145, 95% CI: -9.643 to -0.472), and RT at 610 METs-min/week (MD: -2.187, 95% CI: -3.161 to -1.278), respectively. However, no effective doses are found for Aerobic Exercise (AE), Balance Gait Training (BGT), Dance, and Treadmill Training (TT). Mind-body exercise (MBE) shows promise with an effective range of 130 to 750 METs-min/week and an optimal dose of 750 METs-min/week (MD: -2.822, 95% CI: -4.604 to -0.996). According to the GRADE system, the included studies' overall quality of the evidence was identified moderate level. Conclusion: This study identifies specific exercise modalities and dosages that significantly enhance TUG performance in PD patients. AQE emerges as the most effective modality, with an optimal dosage of 1,500 METs-min/week. MBE shows significant benefits at lower dosages, catering to patients with varying exercise capacities. RT exhibits a nuanced "U-shaped" dose-response relationship, suggesting an optimal range balancing efficacy and the risk of overtraining. These findings advocate for tailored exercise programs in PD management, emphasizing personalized prescriptions to maximize outcomes.Systematic Review Registration: International Prospective Register of Systematic Reviews (PROSPERO) (CRD42024506968).

Effects of exoskeleton-assisted walking on bowel function in motor-complete spinal cord injury patients: involvement of the brain-gut axis, a pilot study.

Evidence has demonstrated that exoskeleton robots can improve intestinal function in patients with spinal cord injury (SCI). However, the underlying mechanisms remain unelucidated. This study investigated the effects of exoskeleton-assisted walking (EAW) on intestinal function and intestinal flora structure in T2-L1 motor complete paraplegia patients. The results showed that five participants in the EAW group and three in the conventional group reported improvements in at least one bowel management index, including an increased frequency of bowel evacuations, less time spent on bowel management per day, and less external assistance (manual digital stimulation, medication, and enema usage). After 8 weeks of training, the amount of glycerol used in the EAW group decreased significantly (p <0.05). The EAW group showed an increasing trend in the neurogenic bowel dysfunction (NBD) score after 8 weeks of training, while the conventional group showed a worsening trend. Patients who received the EAW intervention exhibited a decreased abundance of Bacteroidetes and Verrucomicrobia, while Firmicutes, Proteobacteria, and Actinobacteria were upregulated. In addition, there were decreases in the abundances of Bacteroides, Prevotella, Parabacteroides, Akkermansia, Blautia, Ruminococcus 2, and Megamonas. In contrast, Ruminococcus 1, Ruminococcaceae UCG002, Faecalibacterium, Dialister, Ralstonia, Escherichia-Shigella, and Bifidobacterium showed upregulation among the top 15 genera. The abundance of Ralstonia was significantly higher in the EAW group than in the conventional group, and Dialister increased significantly in EAW individuals at 8 weeks. This study suggests that EAW can improve intestinal function of SCI patients in a limited way, and may be associated with changes in the abundance of intestinal flora, especially an increase in beneficial bacteria. In the future, we need to further understand the changes in microbial groups caused by EAW training and all related impact mechanisms, especially intestinal flora metabolites. Clinical trial registration: https://www.chictr.org.cn/.

A self-healing thermogelling polymer with tunable transparency based on biomolecule alginate grafting phenylboronic acid.

Thermogelling polymers with transparency, structure stability and biocompatibility are promising for biomedicine application. In this study, a thermogelling polymer P-C5PEG with tunable transparency was developed by the reaction between alternating copolymer C5PEG and chemically modified biomolecule Alg-PBA via boronic ester bonds. The sol-to-gel transition of P-C5PEG aqueous solution sensitively responded to changes in temperature, and the critical value could be adjusted between 15 and 40 °C by varying the content of C5PEG and Alg-PBA. As the weight ratio of Alg-PBA to C5PEG was over 0.3, the transparency of as-synthesized hydrogel kept above 75 % at 37 °C. Meanwhile, immersion P-C5PEG hydrogel in CaCl2 solution significantly increased its mechanical strength by 3 times due to chelation effect. The shear-resistance and self-healing properties were ensured by dynamic boronic ester bonds due to the protective effect of hydrophobic gel network. As a drug delivery, P-C5PEG hydrogel had a swelling rate of 3748.7 ± 103 % in PBS and could continuously release fluorescein sodium within 24 h. Moreover, the in vitro degradability and cytotoxicity of P-C5PEG was confirmed. Finally, the mechanisms behind the thermogelling property and tunable transparency were revealed. Overall, this thermogelling P-C5PEG polymer, with tunable transparency and thermo-responsiveness, exhibits great potential for biomedicine application.

Extracellular vesicles originating from steatotic hepatocytes promote hepatic stellate cell senescence via AKT/mTOR signaling.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing rapidly due to the obesity epidemic. In the inflammatory stages of MASLD (MASH), activation of hepatic stellate cells (HSCs) leads to initiation and progression of liver fibrosis. Extracellular vesicles (EVs) are released from all cell types and play an important role in intercellular communication. However, the role of EVs released from hepatocytes in the context of MASLD is largely unknown. Therefore, the present study aimed to investigate the role of EVs derived from both normal and steatotic (free fatty acid-treated) hepatocytes on the phenotype of HSCs via the senescence pathway. Primary rat hepatocytes were treated with free fatty acids (FFAs: oleic acid and palmitic acid). EVs were collected by ultracentrifugation. EVs markers and HSCs activation and senescence markers were assessed by Western blot analysis, qPCR and cytochemistry. Reactive oxygen species (ROS) production was assessed by fluorescence assay. RNA profiles of EVs were evaluated by sequencing. We found that EVs from hepatocytes treated with FFAs (FFA-EVs) inhibit collagen type 1 and α-smooth muscle actin expression, increase the production of ROS and the expression of senescence markers (IL-6, IL-1ß, p21 and senescence-associated ß-galactosidase activity) in early activating HSCs via the AKT-mTOR pathway. Sequencing showed differentially enriched RNA species between the EVs groups. In conclusion, EVs from FFA-treated hepatocytes inhibit HSC activation by inducing senescence via the AKT-mTOR signaling pathway. Determining the components in EVs from steatotic hepatocytes that induce HSC senescence may lead to the identification of novel targets for intervention in the treatment of MASLD in the future.

Double loading of nickel phosphide surface for efficient hydrogen evolution reaction.

Metal phosphide, as a highly conductive, chemically stable catalyst material, modulating its hydrogen adsorption is crucial to enhance hydrogen evolution reaction (HER) activity. In this study, we propose a double loading strategy to build Ag and AgP2 heterogeneous structures on Ni2P nanosheets (Ag-AgP2/Ni2P). This is the first application of AgP2 materials in HER. This innovative synthesis was achieved by liquid-phase adsorption of precursors and heat-treatment phosphorization, surface adsorbed AgNO3 is converted to Ag-AgP2 double loading at the same time as Ni2P formation. Density functional theory (DFT) calculations reveal that the double loading structure optimizes charge distribution and d-band center. Its hydrogen adsorption free energy is closer to electroneutrality than that of single loading and simple heterostructures. Benefiting from the special structure, Ag-AgP2/Ni2P exhibits excellent HER performance in alkaline media, requiring only 78 mV overpotential to reach 10 mA cm-2 and stability up to 200 h. This dual loading strategy broadens the perspective of heterogeneous electrocatalyst development.

Expression pattern of serum interleukin-7 in elderly septic patients and its prognostic value for predicting short-term mortality.

BACKGROUND: The identification of novel prognostic biomarkers in elderly septic patients are essential for the improvement of mortality in sepsis in the context of precision medicine. The purpose of this study was to explore the expression pattern and prognostic value of serum interleukin-7 (IL-7) in predicting 28-day mortality in elderly patients with sepsis. METHODS: Patients were retrospectively enrolled according to the sepsis-3.0 diagnostic criteria and divided into the survival group and non-survival group based on the clinical outcome at the 28-day interval. The baseline characteristic data, samples for the laboratory tests, and the SOFA, Acute Physiology and Chronic Health Evaluation (APACHE II), as well as Glasgow coma scale (GCS) scores, were recorded within 24 h after admission to the emergency department. Serum levels of IL-7 and TNF-α of the patients were quantified by the Luminex assay. Spearman correlation analysis, logistic regressive analysis and receiver operating characteristic curve (ROC) analysis were performed, respectively. RESULTS: Totally, 220 elderly patients with sepsis were enrolled, 151 of whom died in a 28-day period. Albumin (ALB), high-density lipoprotein (HDL), systolic pressure (SBP), and platelet (PLT) were found to be significantly higher in the survival group (p < 0.05). IL-7 was shown to be correlated with TNF-α in the non-survival group (p = 0.030) but not in the survival group (p = 0.194). No correlation was shown between IL-7 and other factors (p > 0.05). IL-7 and TNF-α were found to be independent risk factors associated with the 28-day mortality (OR = 1.215, 1.420). Combination of IL-7, SOFA and ALB can make an AUROC of 0.874 with the specificity of 90.77 %. Combination of IL-7 and TNF-α can make an AUROC of 0.901 with the sensitivity of 90.41 % while the combination of IL-7, TNF-α, and ALB can make an AUROC of 0.898 with the sensitivity of 94.52 %. CONCLUSIONS: This study highlights the importance of monitoring the serum level of IL-7 and TNF-α in elderly septic patients as well as evaluating the combinations with other routine risk factors which can be potentially used for the identification of elderly septic patients with higher risk of mortality.

In-Sb Covalent Bonds over Sb2Se3/In2Se3 Heterojunction for Enhanced Photoelectrochemical Water Splitting.

Antimony selenide is a promising P-type photocatalyst, but it has a large number of deep energy level defects, leading to severe carrier recombination. The construction of a heterojunction is a common way to resolve this problem. However, the conventional heterojunction system inevitably introduces interface defects. Herein, we employ in situ synthesis to epitaxially grow In2Se3 nanosheets on Sb2Se3 nanorods and form In-Sb covalent interfacial bonds. This petal-shaped heterostructure reduced interface defects and enhanced the efficiency of carrier separation and transport. In this work, the photocurrent density in the proposed Sb2Se3/In2Se3 photocathode is 0.485 mA cm-2 at 0 VRHE, which is 30 times higher than that of pristine Sb2Se3 and it has prominent long-term stability for 24 h without obvious decay. The results reveal that the synergy of the bidirectional built-in electric field constructed between In2Se3 and Sb2Se3 and the solid In-Sb interfacial bonds together build a high-efficiency transport channel for the photogenerated carriers that display enhanced photoelectrochemical (PEC) water-splitting performance. This work provides efficient guidance for reducing interface defects via the in situ synthesis and construction of interfacial bonds.

Little ones can do big things: Small molecule inhibitors target PTPN2/PTPN1 for tumor immunotherapy.

AC484 was developed by designing compounds based on the PTPN2 protein structure. AC484 enhances antitumor immunity through multiple mechanisms: increasing tumor sensitivity to IFN-γ, improving T-cell functions, stimulating tumor microenvironment inflammation, expanding TCR diversity, and preventing T-cell exhaustion. Interestingly, the efficacy of AC484 was also mediated by CD8+ and NK cells.

Mechanisms of secondary biogenic coalbed methane formation in bituminous coal seams: a joint experimental and multi-omics study.

Coal seam microbes, as endogenous drivers of secondary biogenic gas production in coal seams, might be related to methane production in coal seams. In this study, we carried out anaerobic indoor culture experiments of microorganisms from three different depths of bituminous coal seams in Huainan mining area, and revealed the secondary biogas generation mechanism of bituminous coal seams by using the combined analysis of macro-genome and metabolism multi-omics. The results showed that the cumulative mass molar concentrations (Molality) of biomethane production increased with the increase of the coal seam depth in two consecutive cycles. At the genus level, there were significant differences in the bacterial and archaeal community structures corresponding to the three coal seams 1#, 6#, and 9#(p < 0.05). The volatile matter of air-dry basis (Vad) of coal was significantly correlated with differences in genus-level composition of bacteria and archaea, with correlations of R bacterial = 0.368 and R archaeal = 0.463, respectively. Functional gene analysis showed that the relative abundance of methanogenesis increased by 42% before and after anaerobic fermentation cultivation. Meanwhile, a total of 11 classes of carbon metabolism homologues closely related to methanogenesis were detected in the liquid metabolites of coal bed microbes after 60 days of incubation. Finally, the fatty acid, amino acid and carbohydrate synergistic methanogenic metabolic pathway was reconstructed based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The expression level of mcrA gene within the metabolic pathway of the 1# deep coal sample was significantly higher than that of the other two groups (p < 0.05 for significance), and the efficient expression of mcrA gene at the end of the methanogenic pathway promoted the conversion of bituminous coal organic matter to methane. Therefore, coal matrix compositions may be the key factors causing diversity in microbial community and metabolic function, which might be related to the different methane content in different coal seams.