First-line immunotherapy efficacy in advanced squamous non-small cell lung cancer with PD-L1 expression ≥50%: a network meta-analysis of randomized controlled trials.

Objective: The optimal first-line immunotherapy regimen for patients with PD-L1 expression ≥50% in squamous non-small cell lung cancer (Sq-NSCLC) remains uncertain. This study utilized net-work meta-analysis (NMA) to indirectly compare the efficacy of various first-line immuno-therapy regimens in this patient subset. Methods: Systematic searches were conducted across PubMed, the Cochrane Library, Web of Science, and Embase databases for randomized controlled trials reporting overall survival (OS) and progression-free survival (PFS) outcomes. The search spanned from database inception to November 3, 2023. Bayesian network meta-analysis was employed for a comprehen-sive analysis. To ensure scientific rigor and transparency, this study is registered in the Interna-tional Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD42022349712. Results: The NMA encompassed 9 randomized controlled trials (RCTs), involving 2170 patients and investigating 9 distinct immunotherapy regimens. For OS, the combination of camrelizumab and chemotherapy demonstrated the highest probability (36.68%) of efficacy, fol-lowed by cemiplimab (33.86%) and atezolizumab plus chemotherapy (23.87%). Regarding PFS, the camrelizumab and chemotherapy combination had the highest probability (39.70%) of efficacy, followed by pembrolizumab (22.88%) and pembrolizumab plus chemotherapy (17.69%). Compared to chemotherapy, first-line treatment with immune checkpoint inhibitors (ICIs) in Sq-NSCLC pa-tients exhibited significant improvements in OS (HR 0.59, 95% CI 0.47-0.75) and PFS (HR 0.44, 95% CI 0.37-0.52). Conclusion: This study suggests that, for Sq-NSCLC patients with PD-L1 expression ≥50%, the first-line immunotherapy regimen of camrelizumab plus chemotherapy provides superior OS and PFS outcomes. Furthermore, ICIs demonstrate enhanced efficacy compared to chemotherapy in this patient population. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD 42022349712.

GC/MS-based untargeted metabolomics reveals the differential metabolites for discriminating vintage of Chenxiang-type baijiu.

The "outstanding and unique aged aroma" of Chinese Chenxiang-type baijiu (CXB)-Daoguang 25 (DG25) mainly originates from a "extraordinary storage technology" of Mujiuhai (a wooden container), so it is mysterious and interesting. In this study, an untargeted GC/MS-based metabolomics was used to reveals the volatile differential metabolites for discriminating six different vintages of DG25 combing with chemometrics. A total of 100 volatile metabolites (including unknowns) were extracted and identified, including esters (41%), alcohols (10%) and acids (7%) so on. Finally, 33 differential metabolites were identified as aging-markers. Among them, 25 aging-markers showed a downtrend, including 17 esters such as ethyl acetate, ethyl hexanoate and ethyl palmitate so on. Moreover, it was interesting and to further study that furans showed a significant downtrend. Statistically speaking, ethyl benzoate played an important role in discriminating vintage of 1Y and 3Y, and the other 24 differential metabolites with downtrend discriminating the unstored (0Y-aged) DG25. Eight differential metabolites, such as ethyl octanoate, benzaldehyde, 3-methylbutanol and 1,1-diethoxyaccetal so on increased during aging of DG25, and they played a statistical role in discriminating the 5Y-, 10Y- and 20Y-aged DG25. This study provides a theoretical basis way for the formation mechanism of aging aroma for CXB.

Poor healthy lifestyle and life's essential 8 are associated with higher risk of new-onset migraine: a prospective cohort study.

BACKGROUND: Lifestyle are closely related to migraine. However, there is a lack of studies investigating the association between Healthy lifestyle or Life's Essential 8 (LE8) and the risk of migraine. The objective of this research was to investigate the relationship between Healthy lifestyle scores and Life's essential 8 scores, and migraine. METHODS: 332,895 UK Biobank participants without migraine were included. Healthy lifestyle were assessed using seven lifestyle factors, and categorized as poor, intermediate, or ideal. LE8, based on the American Heart Association (AHA) Guidelines for Cardiovascular Health (CVH), consist of eight indicators classified as low, moderate, or high CVH. The Cox proportional hazard model was employed to examine the association between Healthy lifestyle scores, LE8 scores, and migraine, with calculations for population-attributable fraction (PAF) and cumulative incidence. RESULTS: During a median follow-up of 13.58 years, participants in intermediate (HR: 0.91; 95% CI: 0.85, 0.99) or ideal category of Healthy lifestyle (HR: 0.81; 95% CI: 0.73, 0.91) significantly reduced migraine risk compared to the poor category. Similarly, high CVH (HR: 0.73; 95% CI: 0.58, 0.92) also lowered migraine risk, while moderate CVH (HR: 0.93; 95% CI: 0.85, 1.02) did not show a difference compared to low CVH. If all individuals adhered to higher categories of Healthy lifestyle and LE8, approximately 11.38% and 22.05% of migraine cases could be prevented. Among individual lifestyle factors, maintaining an ideal body mass index (BMI), physical activity, sleep duration, sleep pattern, and sedentary time were associated with substantial reductions in migraine risk, by 5.65%, 0.81%, 10.16%, 16.39%, and 6.57%, respectively. CONCLUSION: Our study provides evidence that poor Healthy lifestyle and Life's Essential 8 are associated with higher risk of new-onset migraine.

Aqueous AlCl3/ZnCl2 solution room-induced the self-growing strategy of expanded topological network for cellulose/polyacrylamide-based solid-state electrolytes.

The green synthesis strategy for cellulose-containing hydrogel electrolytes is significant for effectively managing resources, energy, and environmental concerns in the contemporary world. Herein, we propose an all-green strategy using AlCl3/ZnCl2/H2O solvent to create cellulose/polyacrylamide-based hydrogel (AZ-Cel/PAM) with expanded hierarchical topologies. The aqueous AlCl3/ZnCl2 facilitates the efficient dissolution of cellulose at room temperature, and the dispersed Al3+-Zn2+ ions autocatalytic system catalyzes in-situ polymerization of acrylamide (AM) monomer. This expands the AM network within the cellulose framework, forming multiple bonding interactions and stable ion channels. The resulting hybrid hydrogel exhibits improved mechanical properties (tensile strength of 56.54 kPa and compressive strength of 359.43 kPa) and enhanced ionic conductivity (1.99 S/m). Furthermore, it also demonstrates excellent adhesion, freeze resistance (-45 °C), and water retention capabilities. Quantum simulations further clarify the mechanical composition and ion transport mechanism of AZ-Cel/PAM hydrogels. The assembled supercapacitor with the hydrogel electrolyte, demonstrates an ideal area-specific capacitance of 203.80 mF/cm2. This all-green strategy presents a novel approach to developing sustainable energy storage devices.

Two telomere-to-telomere gapless genomes reveal insights into Capsicum evolution and capsaicinoid biosynthesis.

Chili pepper (Capsicum) is known for its unique fruit pungency due to the presence of capsaicinoids. The evolutionary history of capsaicinoid biosynthesis and the mechanism of their tissue specificity remain obscure due to the lack of high-quality Capsicum genomes. Here, we report two telomere-to-telomere (T2T) gap-free genomes of C. annuum and its wild nonpungent relative C. rhomboideum to investigate the evolution of fruit pungency in chili peppers. We precisely delineate Capsicum centromeres, which lack high-copy tandem repeats but are extensively invaded by CRM retrotransposons. Through phylogenomic analyses, we estimate the evolutionary timing of capsaicinoid biosynthesis. We reveal disrupted coding and regulatory regions of key biosynthesis genes in nonpungent species. We also find conserved placenta-specific accessible chromatin regions, which likely allow for tissue-specific biosynthetic gene coregulation and capsaicinoid accumulation. These T2T genomic resources will accelerate chili pepper genetic improvement and help to understand Capsicum genome evolution.

Genome-Wide Identification, Phylogenetic and Expression Analysis of Expansin Gene Family in Medicago sativa L.

Expansins, a class of cell-wall-loosening proteins that regulate plant growth and stress resistance, have been studied in a variety of plant species. However, little is known about the Expansins present in alfalfa (Medicago sativa L.) due to the complexity of its tetraploidy. Based on the alfalfa (cultivar "XinjiangDaye") reference genome, we identified 168 Expansin members (MsEXPs). Phylogenetic analysis showed that MsEXPs consist of four subfamilies: MsEXPAs (123), MsEXPBs (25), MsEXLAs (2), and MsEXLBs (18). MsEXPAs, which account for 73.2% of MsEXPs, and are divided into twelve groups (EXPA-I-EXPA-XII). Of these, EXPA-XI members are specific to Medicago trunctula and alfalfa. Gene composition analysis revealed that the members of each individual subfamily shared a similar structure. Interestingly, about 56.3% of the cis-acting elements were predicted to be associated with abiotic stress, and the majority were MYB- and MYC-binding motifs, accounting for 33.9% and 36.0%, respectively. Our short-term treatment (≤24 h) with NaCl (200 mM) or PEG (polyethylene glycol, 15%) showed that the transcriptional levels of 12 MsEXPs in seedlings were significantly altered at the tested time point(s), indicating that MsEXPs are osmotic-responsive. These findings imply the potential functions of MsEXPs in alfalfa adaptation to high salinity and/or drought. Future studies on MsEXP expression profiles under long-term (>24 h) stress treatment would provide valuable information on their involvement in the response of alfalfa to abiotic stress.

An Effect of Chronic Negative Stress on Hippocampal Structures and Functional Connectivity in Patients with Depressive Disorder.

Purpose: Depressive disorder is a mental health disorder with complicated etiopathogenesis. Environmental stress and neurodevelopment combined with other factors contribute to the occurrence of depression. Especially for the depressive disorder with chronic negative stress, it has characteristics of recurrence and poor curative effect because of unclear mechanism. Here, we investigated the hippocampal structures and functional connectivity (FC) according to resting-state functional magnetic resonance imaging in patients with depression who underwent chronic negative stress. Patients and Methods: A total of 65 patients with depression (34 underwent chronic negative stress and 31 non-underwent chronic negative stress) and 30 healthy controls who did not undergo chronic negative stress were included in the study. The volumes of hippocampal subfields, seed-based FCs between hippocampus and the whole brain voxels, and ROI-wise-based FC between hippocampal subfields were compared among the three groups. Results: In the patients with depression who underwent chronic negative stress, the volumes of right_GC-ML-DG-head, right_CA4-head and right_CA3-head increased, FCs between Temporal_Mid_R, Precuneus_R, Frontal_Sup_R, Temporal_Sup_R, Angular_L, Frontal_Inf_Tri_R, Supp_Motor_Area_R, Precentral_L and hippocampus increased, and FCs between parasubiculum and CA3, and presubiculum and CA1 decreased. When compared to the patients who did not undergo chronic negative stress, the patients who underwent chronic negative stress had larger volumes of right_GC-ML-DG-head and right_CA3-head, higher FCs between Frontal_Sup_R, Frontal_Inf_Tri_R and hippocampus, and lower FCs between presubiculum and CA1. Conclusion: The depression underwent chronic negative stress may experience disrupted hippocampal structures and functional connectivity. It may be one of potential depressive disorder subtypes.

Comprehensive analysis of immune-related lncRNAs in AML patients uncovers potential therapeutic targets and prognostic biomarkers.

Purpose: The objective of this study was to provide theoretically feasible strategies by understanding the relationship between the immune microenvironment and the diagnosis and prognosis of AML patients. To this end, we built a ceRNA network with lncRNAs as the core and analyzed the related lncRNAs in the immune microenvironment by bioinformatics analysis. Methods: AML transcriptome expression data and immune-related gene sets were obtained from TCGA and ImmPort. Utilizing Pearson correlation analysis, differentially expressed immune-related lncRNAs were identified. Then, the LASSO-Cox regression analysis was performed to generate a risk signature consisting immune-related lncRNAs. Accuracy of signature in predicting patient survival was evaluated using univariate and multivariate analysis. Next, GO and KEGG gene enrichment and ssGSEA were carried out for pathway enrichment analysis of 183 differentially expressed genes, followed by drug sensitivity and immune infiltration analysis with pRRophetic and CIBERSORT, respectively. Cytoscape was used to construct the ceRNA network for these lncRNAs. Results: 816 common lncRNAs were selected to acquire the components related to prognosis. The final risk signature established by multivariate Cox and stepwise regression analysis contained 12 lncRNAs engaged in tumor apoptotic and metastatic processes: LINC02595, HCP5, AC020934.2, AC008770.3, LINC01770, AC092718.4, AL589863.1, AC131097.4, AC012368.1, C1RL-AS1, STARD4-AS1, and AC243960.1. Based on this predictive model, high-risk patients exhibited lower overall survival rates than low-risk patients. Signature lncRNAs showed significant correlation with tumor-infiltrating immune cells. In addition, significant differences in PD-1/PD-L1 expression and bleomycin/paclitaxel sensitivity were observed between risk groups. Conclusion: LncRNAs related to immune microenvironment were prospective prognostic and therapeutic options for AML.

Investigating the role of TGF-ß and BDNF in cancer-related depression: a primary cross-sectional study.

BACKGROUND: Cancer-related depression is a well-documented condition that significantly impacts long-term quality of life. Brain-derived neurotrophic factor (BDNF), a neurotrophin essential for neurogenesis and neuronal plasticity, has been implicated in various neuropsychological disorders including depression associated with cancer. Cytokines, on the other hand, play a crucial role in regulating depression, potentially by influencing BDNF expression. Transforming growth factor-ß (TGF-ß), a key immune regulator within the tumor microenvironment, has been found to elevate BDNF levels, establishing a link between peripheral immune responses and depression. The study aims to investigate the correlation of TGF-ß and BDNF in cancer-related depression. METHODS: This study involved a cohort of 153 gynecological patients, including 61 patients with gynecological cancer and 92 patients without cancer. Depression levels were assessed using the subscale of Hospital Anxiety and Depression Scale (HADS-D), and TGF-ß and BDNF plasma levels were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: The study revealed elevated plasma TGF-ß levels in patients with cancer (32.24 ± 22.93 ng/ml) compared to those without cancer (25.24 ± 19.72 ng/ml) (P = 0.046). Additionally, reduced levels of BDNF were observed in patients presenting depression symptoms (44.96 ± 41.06 pg/ml) compared to those without depression (133.5 ± 176.7 pg/ml) (P = 0.036). Importantly, a significant correlation between TGF-ß and BDNF was found in patients without cancer but with depression (correlation coefficient = 0.893, **P < 0.01). Interestingly, cancer appeared to influence the association between TGF-ß and BDNF in patients with depression, as evidenced by a significant difference in the correlation of TGF-ß and BDNF between cancer and non-cancer groups (P = 0.041). CONCLUSIONS: These findings underscore the active involvement of TGF-ß and BDNF crosstalk in the context of cancer-related depression.

CD73 polymorphisms are associated with schizophrenia.

Ecto-5'-nucleotidase/CD73 enzyme plays a key role in the regulation of extracellular adenosine levels, thereby exerting influence on adenosine homeostasis. Emerging evidence suggests that perturbations in purines and ecto-5'-nucleotidase activity are associated with an augmented susceptibility to schizophrenia. However, the precise impact of genetic variations in CD73 on individuals with schizophrenia remains poorly understood. Here, our study demonstrated that rs3734442 allele and rs4431401 heterozygote were conferred a significant risk of schizophrenia disease (rs3734442: odds ratio, 0.556; 95% CI, 0.375 to 0.825; p = 0.004; rs4431401: odds ratio, 1.881, 95% CI, 1.117 to 3.166; p = 0.020). Comparing different genders, we observed a significant association between rs3734442 genotypes and male cases (rs3734442: odds ratio, 0.452; 95% CI, 0.257 to 0.796; p = 0.007). Likewise, there was a significant association between rs4431401 genotypes and male patients (rs4431401: odds ratio, 2.570; 95% CI, 1.196 to 5.522; p = 0.015). Based on family history and antipsychotics medication usage, our data reveals that the rs9444348 allele exhibits the most significant association with familial susceptibility to schizophrenia (odds ratio, 1.541; 95% CI, 1.009 to 2.353; p = 0.048 for A vs G). Moreover, individuals carrying variants of rs6922, rs2229523, and rs2065114 while being treated with clozapine demonstrate a higher frequency proportion compared to those receiving risperidone treatment (p = 0.035; p = 0.049; p = 0.027 respectively). Additionally, our results indicate that patients with GG genotype of rs9444348 had significantly higher likelihood of using clozapine instead of sulpiride (p = 0.048). Overall, our data strongly suggest that genetic variations in CD73 are significantly associated with schizophrenia risk and may serve as valuable resources for identifying therapeutic targets.

Exploring Central and Bridge Symptoms in Patients with Lung Cancer: A Network Analysis.

OBJECTIVES: This study aimed to identify symptom clusters in lung cancer patients undergoing chemotherapy and the central and bridge symptoms within each symptom cluster. METHODS: In this cross-sectional study, 1,255 patients with lung cancer were recruited through convenience sampling at Nanfang Hospital. Patient symptom burden was assessed using the M.D. Anderson Symptom Inventory (MDASI) and the Lung Cancer module of the MDASI (MDASI-LC). Symptom clusters were identified using the Walktrap algorithm, and central and bridge symptoms in the symptom clusters were identified by network analysis. RESULTS: The patients included 818 (65.18%) males and 437 (34.82%) females with a mean age of 56.56 ± 11.78 years. Four symptom clusters were identified: fatigue, gastrointestinal, psychoneurological and respiratory. Their central symptoms were fatigue, vomiting, distress and hemoptysis, respectively, and their bridge symptoms were pain, vomiting, dry mouth and shortness of breath. CONCLUSIONS: Lung cancer symptoms show certain strong correlations with each other, resulting in symptom clusters. Central symptoms may influence other symptoms within a symptom cluster, and bridge symptoms might impact the density of the symptom network. This study identified central and bridge symptoms in lung cancer patients undergoing chemotherapy. Targeting these symptoms with interventions for symptom clusters could make symptom management more precise and effective. IMPLICATIONS FOR NURSING PRACTICE: In clinical settings, the burden of symptom clusters may be reduced by intervening against the central symptoms of these symptom clusters. Alternatively, if the objective is to diminish the connections between different symptom clusters and holistically alleviate the overall burden, interventions focused on bridge symptoms may be employed.

USP10 alleviates Nε-carboxymethyl-lysine-induced vascular calcification and atherogenesis in diabetes mellitus by promoting AMPK activation.

Vascular calcification (VC) is a characteristic feature in patients with diabetes mellitus (DM) and is closely associated with the osteogenic differentiation of vascular smooth muscle cells (VSMCs). Ubiquitin-Specific Protease 10 (USP10) has been shown to regulate multiple cellular processes; however, its relationship with diabetic VC remains unclear. This study aims to elucidate the role of USP10 in VC development and the underlying regulatory mechanisms. Nε-carboxymethyl lysine (CML) was significantly increased in calcified ateries from diabetic atherosclerosis ApoE-/- mice fed with high-fat diets. CML downregulated USP10 expression in VSMCs and calcified mice coronary arteries, as assessd by Western blotting, RT-qPCR,immunofluorescence and immunohistochemistry. Loss-and gain-of-function experiments were conducted both in vitro and in vivo to verify the biological functions of USP10. Ectopic expression of USP10 mitigated the severity of VC. With regard to the mechanism, the interaction between USP10 and AMPKα was investigated through double-label immunofluorescence and Co-immunoprecipitation. In vitro ubiquitination assay revealed that USP10 was capable of mediating AMPKα ubiquitination and caused increased AMPKα phosphorylation level at Thr172. Moreover, the anticalcification effect of USP10 was reversed by pharmacological inhibition of AMPK signaling pathway. The current fundings suggest an important role of USP10 in diabetic VC progression, at least in part, via mediating the ubiquitination and activation of AMPKα. USP10 may serve as a novel therapeutic target for the treatment of diabetic VC.

Bioinformatics to Identify Biomarkers of Diabetic Nephropathy based on Sphingolipid Metabolism and their Molecular Mechanisms.

ACKGROUND: Diabetes mellitus (DM) frequently results in Diabetic Nephropathy (DN), which has a significant negative impact on the quality of life of diabetic patients. Sphingolipid metabolism is associated with diabetes, but its relationship with DN is unclear. Therefore, screening biomarkers related to sphingolipid metabolism is crucial for treating DN. METHODS: To identify Differentially Expressed Genes (DEGs) in the GSE142153 dataset, we conducted a differential expression analysis (DN samples versus control samples). The intersection genes were obtained by overlapping DEGs and Sphingolipid Metabolism-Related Genes (SMRGs). Furthermore, The Least Absolute Shrinkage and Selection Operator (LASSO) and Support Vector Machine Recursive Feature Elimination (SVM-RFE) algorithms were used to filter biomarkers. We further analyzed the Gene Set Enrichment analysis (GSEA) and the immunoinfiltrational analysis based on biomarkers. RESULTS: We identified 2,186 DEGs associated with DN. Then, five SMR-DEGs were obtained. Subsequently, biomarkers associated with sphingolipid metabolism (S1PR1 and SELL) were identified by applying machine learning and expression analysis. In addition, GSEA showed that these biomarkers were correlated with cytokine cytokine receptor interaction'. Significant variations in B cells, DCs, Tems, and Th2 cells between the two groups suggested that these cells might have a role in DN. CONCLUSION: Overall, we obtained two sphingolipid metabolism-related biomarkers (S1PR1 and SELL) associated with DN, which laid a theoretical foundation for treating DN.

Cardiac function evaluation in children with spinal muscular atrophy: A case-control study.

BACKGROUND: Spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by degeneration of lower motor neurons, resulting in progressive muscle weakness and atrophy. However, little is known regarding the cardiac function of children with SMA. METHODS: We recruited SMA patients younger than 18 years of age from January 1, 2022, to April 1, 2022, in the First Affiliated Hospital of Sun Yat-sen University. All patients underwent a comprehensive cardiac evaluation before treatment, including history taking, physical examination, blood tests of cardiac biomarkers, assessment of echocardiography and electrocardiogram. Age/gender-matched healthy volunteers were recruited as controls. RESULTS: A total of 36 SMA patients (26 with SMA type 2 and 10 with SMA type 3) and 40 controls were enrolled in the study. No patient was clinically diagnosed with heart failure. Blood tests showed elevated values of creatine kinase isoenzyme M and isoenzyme B (CK-MB) mass and high-sensitivity cardiac troponin T (hs-cTnT) in spinal muscular atrophy (SMA) patients. Regarding echocardiographic parameters, SMA children were detected with lower global left and right ventricular longitudinal strain, abnormal diastolic filling velocities of trans-mitral and trans-tricuspid flow. The results revealed no clinical heart dysfunction in SMA patients, but subclinical ventricular dysfunction was seen in SMA children including the diastolic function and myocardial performance. Some patients presented with elevated heart rate and abnormal echogenicity of aortic valve or wall. Among these SMA patients, seven patients (19.4%) had scoliosis. The Cobb's angles showed a significant negative correlation with LVEDd/BSA, but no correlation with other parameters, suggesting that mild scoliosis did not lead to significant cardiac dysfunction. CONCLUSIONS: Our findings warrant increased attention to the cardiac status and highlight the need to investigate cardiac interventions in SMA children.

CoPS/Co 4 S 3 Heterojunction with Highly Exposed Active Sites and Dual-site Synergy for Effective Hydrogen Evolution Reactions.

Cobalt phosphosulphide (CoPS) has recently been recognized as a potentially effective electrocatalyst for the hydrogen evolution reaction (HER). However, there have been no research on the design of CoPS-based heterojunctions to boost their HER performance. Herein, CoPS/Co4S3 heterojunction was prepared by phosphating treatment based on defect-rich flower-like Co1-xS precursors. The high specific surface area of nanopetals, together with the heterojunction structure with inhomogeneous strain, exposes more active sites in the catalyst. The electronic structure of the catalyst is reconfigured as a result of the interfacial interactions, which promote the catalyst's ability to adsorb hydrogen and conduct electricity. The synergistic effect of the Co and S dual-site further enhance the catalytic activity. The catalyst has overpotentials of 61 and 70 mV to attain a current density of 10 mA cm-2 in acidic and alkaline media, respectively, which renders it competitive with previously reported analogous catalysts. This work proposes an effective technique for constructing transition metal phosphosulfide heterojunctions, as well as the development of an efficient HER electrocatalyst.

Unraveling transcriptomic signatures and dysregulated pathways in systemic lupus erythematosus across disease states.

OBJECTIVES: This study aims to elucidate the transcriptomic signatures and dysregulated pathways in patients with Systemic Lupus Erythematosus (SLE), with a particular focus on those persisting during disease remission. METHODS: We conducted bulk RNA-sequencing of peripheral blood mononuclear cells (PBMCs) from a well-defined cohort comprising 26 remission patients meeting the Low Lupus Disease Activity State (LLDAS) criteria, 76 patients experiencing disease flares, and 15 healthy controls. To elucidate immune signature changes associated with varying disease states, we performed extensive analyses, including the identification of differentially expressed genes and pathways, as well as the construction of protein-protein interaction networks. RESULTS: Several transcriptomic features recovered during remission compared to the active disease state, including down-regulation of plasma and cell cycle signatures, as well as up-regulation of lymphocytes. However, specific innate immune response signatures, such as the interferon (IFN) signature, and gene modules involved in chromatin structure modification, persisted across different disease states. Drug repurposing analysis revealed certain drug classes that can target these persistent signatures, potentially preventing disease relapse. CONCLUSION: Our comprehensive transcriptomic study revealed gene expression signatures for SLE in both active and remission states. The discovery of gene expression modules persisting in the remission stage may shed light on the underlying mechanisms of vulnerability to relapse in these patients, providing valuable insights for their treatment.

Unlocking Maximum Synergy: Screen-Printing Fabrication of Heterostructured Microsupercapacitor Stacks.

A cost-effective and scalable approach for the fabrication of heterostructured microsupercapacitors (MSCs) employing screen-printing followed by sequential electrochemical and microspray deposition techniques has been demonstrated. The microsupercapacitor electrode (MSC) that composed of stacked layers of mesoporous carbon, polyaniline (PANI), and MXene hold significant promise for wearable electronics. By adjusting the deposition and spray cycles, the MSC can be readily coated with PANI and MXene. The sequentially stacked two layers of MXene and PANI on the mesoporous carbon spheres (PMPM-MSC) yielded a specific capacitance of 1003 mF cm-2 at 0.5 mA cm-2, surpassing the performance of PANI/mesoporous carbon electrode by 1.6 times (771 mF cm-2). After 10,000 cycles of charge and discharge, PMPM-MSCs retained more than 86% of their initial capacitance. In-situ Raman spectroscopy confirmed the synergistic effects between MXene and PANI within the heterostructured stacked PMPM-MSC electrodes, including enhanced electronic conductivity and improved electrolyte ion dissociation, which aligned with the electrochemical measurement results, such as fast charge/discharge rates and reduced internal and mass transport resistance. This study demonstrates the potential of screen-printed heterostructured MSC stacks with maximum electrochemical synergy for portable and wearable energy storage devices.

Life-Long Aerobic Exercise is a Non-Pharmacological Approach for Inducing Autophagy and Delaying Muscle Atrophy in the Aging Population.

Numerous bodily processes deteriorate with age, chief among them being the loss of muscle mass and function. The condition referred to as aging myasthenia gravis impairs older persons' quality of life and is linked to a higher risk of several chronic illnesses. An increasing number of studies conducted in the last several years has demonstrated that moderate exercise can halt this process. Specifically, by promoting autophagy, aerobic exercise helps to postpone the onset of senile myasthenia gravis. In this work, we will explore how aerobic exercise modulates autophagy to prevent muscle aging and examine the most recent findings in this area of study. We discovered that exercise-induced autophagy can effectively balance protein degradation and relieve skeletal muscle atrophy by looking through pertinent literature. Aerobic exercise has a direct impact on autophagy, but it can also delay the onset of senile myasthenia gravis by enhancing blood flow, lowering inflammation, and boosting muscle oxidative capacity. In order to postpone the onset of senile myasthenia gravis, research on the mechanism of action of aerobic exercise in inducing autophagy will be discussed in detail in this study.

Association between early spontaneous abortion and homocysteine metabolism.

Objective: The purpose of this study is to explore the effects of homocysteine (HCY) metabolism and related factors on early spontaneous abortion. Methods: We conducted a hospital-based case-control study and included a total of 500 cases and 1,000 controls in Shaanxi China. Pregnant women waiting for delivery in the hospital were interviewed to report their characteristics and other relevant information during pregnancy. The unconditional Logisitic regression model was applied to assess the association between early spontaneous abortion and HCY metabolism and related factors. The multiplicative model was applied to assess the effects of interaction of HCY metabolism and related factors on early spontaneous abortion. The logit test method of generalized structural equation model (GSEM) was used to construct the pathway diagram of HCY metabolism and related factors affecting early spontaneous abortion. Results: Folic acid supplementation and adequate folic acid supplementation during periconception were the protective factors of early spontaneous abortion (OR = 0.50, 95% CI: 0.38-0.65; OR = 0.44, 95% CI: 0.35-0.54). The serum folate deficiency, higher plasma HCY in early pregnancy, the women who carried the MTHFR 677TT genotype were the risk factors of early spontaneous abortion (OR = 5.87, 95% CI: 1.53-22.50; OR = 2.94, 95% CI: 1.14-7.57; OR = 2.32, 95% CI: 1.20-4.50). The women's educational level and maternal and child health care utilization affected the occurrence of early spontaneous abortion by influencing the folic acid supplementation during periconception. The folic acid supplementation during periconception affected the occurrence of early spontaneous abortion by influencing the level of serum folate or plasma HCY in early pregnancy. The maternal MTHFR 677 gene polymorphism affected the occurrence of early spontaneous abortion by influencing the level of serum folate in early pregnancy. In terms of the risks for early spontaneous abortion, there was multiplicative interaction between higher plasma HCY in early pregnancy, serum folate deficiency in early pregnancy and maternal MTHFR 677TT genotype (OR = 1.76, 95% CI: 1.17-4.03), and there was multiplicative interaction between higher plasma HCY and serum folate deficiency in early pregnancy (OR = 3.46, 95% CI: 2.49-4.81), and there was multiplicative interaction between serum folate deficiency in early pregnancy and maternal MTHFR 677TT genotype (OR = 3.50, 95% CI: 2.78-5.18). The above interactions are all synergistic. The occurrence risk of early spontaneous abortion was significantly increased if multiple factors existed at the same time. Conclusion: Our study is the first time to construct the pathway of HCY metabolism and related factors affecting early spontaneous abortion, and provides a comprehensively new idea to prevent and reduce the occurrence of spontaneous abortion.

Intervention model under the Omaha system framework can effectively improve the sleep quality and negative emotion of patients with mid to late-stage lung cancer and is a protective factor for quality of life.

This study aims to evaluate the effects of Omaha System framework interventions on quality of life, emotional well-being, and sleep quality in 507 mid to late-stage lung cancer patients. Retrospectively, we compared data of 294 patients receiving conventional care (conventional group) with 213 patients undergoing Omaha System interventions (intervention group) from January 2019 to January 2023. Key indicators included quality of life (FACT-L), anxiety (SAS), depression (SDS), sleep quality (PSQI), hope (HHS), and dignity (PDI). Post-intervention, the intervention group showed a significant increase in FACT-L scores (P<0.001), indicating enhanced quality of life. There was a notable reduction in PSQI scores (P<0.001), suggesting improved sleep quality. Additionally, their anxiety and depression levels significantly decreased, as evidenced by lower SAS (P<0.001) and SDS scores (P<0.001). Logistic regression revealed that care nursing intervention scheme (P=0.007), age (P=0.008), marital status (P=0.002), per capita monthly household income (P=0.004), SAS after intervention (P=0.002), and PSQI after intervention (P=0.002) had a positive influence on quality of life. In conclusion, the Omaha System interventions markedly improved the quality of life, emotional state, and sleep in lung cancer patients.