Uncoupling of macrophage inflammation from self-renewal modulates host recovery from respiratory viral infection.

Tissue macrophages self-renew during homeostasis and produce inflammatory mediators upon microbial infection. We examined the relationship between proliferative and inflammatory properties of tissue macrophages by defining the impact of the Wnt/ß-catenin pathway, a central regulator of self-renewal, in alveolar macrophages (AMs). Activation of ß-catenin by Wnt ligand inhibited AM proliferation and stemness, but promoted inflammatory activity. In a murine influenza viral pneumonia model, ß-catenin-mediated AM inflammatory activity promoted acute host morbidity; in contrast, AM proliferation enabled repopulation of reparative AMs and tissue recovery following viral clearance. Mechanistically, Wnt treatment promoted ß-catenin-HIF-1α interaction and glycolysis-dependent inflammation while suppressing mitochondrial metabolism and thereby, AM proliferation. Differential HIF-1α activities distinguished proliferative and inflammatory AMs in vivo. This ß-catenin-HIF-1α axis was conserved in human AMs and enhanced HIF-1α expression associated with macrophage inflammation in COVID-19 patients. Thus, inflammatory and reparative activities of lung macrophages are regulated by ß-catenin-HIF-1α signaling, with implications for the treatment of severe respiratory diseases.

The Transcription Factor Bhlhe40 Programs Mitochondrial Regulation of Resident CD8+ T Cell Fitness and Functionality.

Tissue-resident memory CD8+ T (Trm) cells share core residency gene programs with tumor-infiltrating lymphocytes (TILs). However, the transcriptional, metabolic, and epigenetic regulation of Trm cell and TIL development and function is largely undefined. Here, we found that the transcription factor Bhlhe40 was specifically required for Trm cell and TIL development and polyfunctionality. Local PD-1 signaling inhibited TIL Bhlhe40 expression, and Bhlhe40 was critical for TIL reinvigoration following anti-PD-L1 blockade. Mechanistically, Bhlhe40 sustained Trm cell and TIL mitochondrial fitness and a functional epigenetic state. Building on these findings, we identified an epigenetic and metabolic regimen that promoted Trm cell and TIL gene signatures associated with tissue residency and polyfunctionality. This regimen empowered the anti-tumor activity of CD8+ T cells and possessed therapeutic potential even at an advanced tumor stage in mouse models. Our results provide mechanistic insights into the local regulation of Trm cell and TIL function.

Physical exercise in liver diseases.

Liver diseases contribute to ~2 million deaths each year and account for 4% of all deaths globally. Despite various treatment options, the management of liver diseases remains challenging. Physical exercise is a promising nonpharmacological approach to maintain and restore homeostasis and effectively prevent and mitigate liver diseases. In this review, we delve into the mechanisms of physical exercise in preventing and treating liver diseases, highlighting its effects on improving insulin sensitivity, regulating lipid homeostasis, and modulating immune function. In addition, we evaluate the impact of physical exercise on various liver diseases, including liver ischemia/reperfusion injury, cardiogenic liver disease, metabolic dysfunction-associated steatotic liver disease, portal hypertension, cirrhosis, and liver cancer. In conclusion, the review underscores the effectiveness of physical exercise as a beneficial intervention in combating liver diseases.

Establishment of patient-derived organoids for guiding personalized therapies in breast cancer patients.

Breast cancer has become the most commonly diagnosed cancer. The intra- and interpatient heterogeneity induced a considerable variation in treatment efficacy. There is an urgent requirement for preclinical models to anticipate the effectiveness of individualized drug responses. Patient-derived organoids (PDOs) can accurately recapitulate the architecture and biological characteristics of the origin tumor, making them a promising model that can overtake many limitations of cell lines and PDXs. However, it is still unclear whether PDOs-based drug testing can benefit breast cancer patients, particularly those with tumor recurrence or treatment resistance. Fresh tumor samples were surgically resected for organoid culture. Primary tumor samples and PDOs were subsequently subjected to H&E staining, immunohistochemical (IHC) analysis, and whole-exome sequencing (WES) to make comparisons. Drug sensitivity tests were performed to evaluate the feasibility of this model for predicting patient drug response in clinical practice. We established 75 patient-derived breast cancer organoid models. The results of H&E staining, IHC, and WES revealed that PDOs inherited the histologic and genetic characteristics of their parental tumor tissues. The PDOs successfully predicted the patient's drug response, and most cases exhibited consistency between PDOs' drug susceptibility test results and the clinical response of the matched patient. We conclude that the breast cancer organoids platform can be a potential preclinical tool used for the selection of effective drugs and guided personalized therapies for patients with advanced breast cancer.

Gustative Roussy Immune Score is a Predictor for Major Pathological Response in Rectal Cancer: A Result from the Preoperative Intraarterial Chemoembolization Combined with Radiotherapy (PCAR) Study.

Despite the emergence of various treatment strategies for rectal cancer based on neoadjuvant chemoradiotherapy, there is currently a lack of reliable biomarkers to determine which patients will respond well to neoadjuvant chemoradiotherapy. Through collecting hematological and biochemical parameters data of patients prior to receiving neoadjuvant chemoradiotherapy, we evaluated the predictive value of systemic inflammatory indices for pathological response and prognosis in rectal cancer patients. We found that baseline GRIm-Score was an independent predictor for MPR in rectal cancer patients. However, no association was observed between several commonly systemic inflammation indices and long-term outcome.

TFAM-Dependent Mitochondrial Metabolism Is Required for Alveolar Macrophage Maintenance and Homeostasis.

Alveolar macrophages (AMs) are major lung tissue-resident macrophages capable of proliferating and self-renewal in situ. AMs are vital in pulmonary antimicrobial immunity and surfactant clearance. The mechanisms regulating AM compartment formation and maintenance remain to be fully elucidated currently. In this study, we have explored the roles of mitochondrial transcription factor A (TFAM)-mediated mitochondrial fitness and metabolism in regulating AM formation and function. We found that TFAM deficiency in mice resulted in significantly reduced AM numbers and impaired AM maturation in vivo. TFAM deficiency was not required for the generation of AM precursors nor the differentiation of AM precursors into AMs, but was critical for the maintenance of AM compartment. Mechanistically, TFAM deficiency diminished gene programs associated with AM proliferation and self-renewal and promoted the expression of inflammatory genes in AMs. We further showed that TFAM-mediated AM compartment impairment resulted in defective clearance of cellular debris and surfactant in the lung and increased the host susceptibility to severe influenza virus infection. Finally, we found that influenza virus infection in AMs led to impaired TFAM expression and diminished mitochondrial fitness and metabolism. Thus, our data have established the critical function of TFAM-mediated mitochondrial metabolism in AM maintenance and function.

Workplace violence and depressive symptoms: the mediating role of fear of future workplace violence and burnout among Chinese nurses.

BACKGROUND: The mechanisms underlying the relationship between workplace violence (WPV) and depressive symptoms in nurses have been less studied. This study aims to examine the mediating role of fear of future workplace violence (FFWV) and burnout in the association between WPV and depressive symptoms. METHODS: We conducted a cross-sectional web survey at 12 tertiary hospitals in Shandong province, China, in 2020. The Center for Epidemiologic Studies Depression Scale (CESD-10), the Chinese version of the Maslach Burnout Inventory-General Survey and the Fear of Future Violence at Work Scale were used to collect data. Descriptive statistics, independent sample t-test, one-way analysis of variance, Pearson's correlation coefficient, and ordinary least squares regression with bootstrap resampling were used to analyze the data. RESULTS: The prevalence of depressive symptoms was 45.9% among nurses. The regression model showed that FFWV and burnout mediated the relationship between WPV and depressive symptoms. The total effects of WPV on depressive symptoms (3.109, 95% bootstrap CI:2.324 - 3.713) could be decomposed into direct (2.250, 95% bootstrap CI:1.583 - 2.917) and indirect effects (0.769, 95% bootstrap CI:0.543 - 1.012). Indirect effects mediated by FFWV and burnout were 0.203 (95% bootstrap CI:0.090 - 0.348) and 0.443 (95% bootstrap CI:0.262 - 0.642), respectively. Furthermore, serial multiple mediation analyses indicated that the indirect effect mediated by FFWV and burnout in a sequential manner was 0.123 (95% bootstrap CI:0.070 - 0.189). CONCLUSION: The prevalence of depressive symptoms among Chinese nurses was high. The WPV was an important risk factor for depressive symptoms and its negative effect was mediated by FFWV and burnout. The importance of decreasing WPV exposure and level of FFWV and burnout was emphasized to prevent depressive symptoms among nurses. The findings implied that hospital managers and health policy makers should not only develop targeted interventions to reduce exposure to WPV in daily work among all nurses, but also provide psychological support to nurses with WPV experience to reduce FFWV and burnout.

Acute kidney injury in hospitalized patients with nonmalignant pleural effusions: a retrospective cohort study.

BACKGROUND: Nonmalignant pleural effusion (NMPE) is common and remains a definite health care problem. Pleural effusion was supposed to be a risk factor for acute kidney injury (AKI). Incidence of AKI in NMPE patients and whether there is correlation between the size of effusions and AKI is unknown. OBJECTIVE: To assess the incidence of AKI in NMPE inpatients and its association with effusion size. STUDY DESIGN AND METHOD: We conducted a retrospective cohort study of inpatients admitted to the Chinese PLA General Hospital with pleural effusion from 2018-2021. All patients with pleural effusions confirmed by chest radiography (CT or X-ray) were included, excluding patients with diagnosis of malignancy, chronic dialysis, end-stage renal disease (ESRD), community-acquired AKI, hospital-acquired AKI before chest radiography, and fewer than two serum creatinine tests during hospitalization. Multivariate logistic regression and LASSO logistic regression models were used to identify risk factors associated with AKI. Subgroup analyses and interaction tests for effusion volume were performed adjusted for the variables selected by LASSO. Causal mediation analysis was used to estimate the mediating effect of heart failure, pneumonia, and eGFR < 60 ml/min/1.73m2 on AKI through effusion volume. RESULTS: NMPE was present in 7.8% of internal medicine inpatients. Of the 3047 patients included, 360 (11.8%) developed AKI during hospitalization. After adjustment by covariates selected by LASSO, moderate and large effusions increased the risk of AKI compared with small effusions (moderate: OR 1.47, 95%CI 1.11-1.94 p = 0.006; large: OR 1.86, 95%CI 1.05-3.20 p = 0.028). No significant modification effect was observed among age, gender, diabetes, bilateral effusions, and eGFR. Volume of effusions mediated 6.8% (p = 0.005), 4.0% (p = 0.046) and 4.6% (p < 0.001) of the effect of heart failure, pneumonia and low eGFR on the development of AKI respectively. CONCLUSION: The incidence of AKI is high among NMPE patients. Moderate and large effusion volume is independently associated with AKI compared to small size. The effusion size acts as a mediator in heart failure, pneumonia, and eGFR.

Baicalein enhances immune response in TNBC by inhibiting leptin expression of adipocytes.

Triple-negative breast cancer (TNBC) is a special pathological type of breast cancer (BC) with poor prognosis. Obesity is shown to be involved in TNBC tumor progression. The interaction between obesity and BC has generated great attention in recent years, however, the mechanism is still unclear. Here, we showed that leptin secreted by adipocytes upregulated PD-L1 expression in TNBC through the p-STAT3 signaling pathway and that baicalein inhibited PD-L1 expression in tumor microenvironment by suppressing leptin transcription of adipocytes. Collectively, our findings suggest that leptin may be the key factor participating in obesity-related tumor progression and that baicalein can break through the dilemma to boost the anti-tumor immune response.

Novel models by machine learning to predict prognosis of breast cancer brain metastases.

BACKGROUND: Breast cancer brain metastases (BCBM) are the most fatal, with limited survival in all breast cancer distant metastases. These patients are deemed to be incurable. Thus, survival time is their foremost concern. However, there is a lack of accurate prediction models in the clinic. What's more, primary surgery for BCBM patients is still controversial. METHODS: The data used for analysis in this study was obtained from the SEER database (2010-2019). We made a COX regression analysis to identify prognostic factors of BCBM patients. Through cross-validation, we constructed XGBoost models to predict survival in patients with BCBM. Meanwhile, a BCBM cohort from our hospital was used to validate our models. We also investigated the prognosis of patients treated with surgery or not, using propensity score matching and K-M survival analysis. Our results were further validated by subgroup COX analysis in patients with different molecular subtypes. RESULTS: The XGBoost models we created had high precision and correctness, and they were the most accurate models to predict the survival of BCBM patients (6-month AUC = 0.824, 1-year AUC = 0.813, 2-year AUC = 0.800 and 3-year survival AUC = 0.803). Moreover, the models still exhibited good performance in an externally independent dataset (6-month: AUC = 0.820; 1-year: AUC = 0.732; 2-year: AUC = 0.795; 3-year: AUC = 0.936). Then we used Shiny-Web tool to make our models be easily used from website. Interestingly, we found that the BCBM patients with an annual income of over USD$70,000 had better BCSS (HR = 0.523, 95%CI 0.273-0.999, P < 0.05) than those with less than USD$40,000. The results showed that in all distant metastasis sites, only lung metastasis was an independent poor prognostic factor for patients with BCBM (OS: HR = 1.606, 95%CI 1.157-2.230, P < 0.01; BCSS: HR = 1.698, 95%CI 1.219-2.365, P < 0.01), while bone, liver, distant lymph nodes and other metastases were not. We also found that surgical treatment significantly improved both OS and BCSS in BCBM patients with the HER2 + molecular subtypes and was beneficial to OS of the HR-/HER2- subtype. In contrast, surgery could not help BCBM patients with HR + /HER2- subtype improve their prognosis (OS: HR = 0.887, 95%CI 0.608-1.293, P = 0.510; BCSS: HR = 0.909, 95%CI 0.604-1.368, P = 0.630). CONCLUSION: We analyzed the clinical features of BCBM patients and constructed 4 machine-learning prognostic models to predict their survival. Our validation results indicate that these models should be highly reproducible in patients with BCBM. We also identified potential prognostic factors for BCBM patients and suggested that primary surgery might improve the survival of BCBM patients with HER2 + and triple-negative subtypes.

Causal effects of COVID-19 on cancer risk: A Mendelian randomization study.

In contemporary literature, little attention has been paid to the association between coronavirus disease-2019 (COVID-19) and cancer risk. We performed the Mendelian randomization (MR) to investigate the causal associations between the three types of COVID-19 exposures (critically ill COVID-19, hospitalized COVID-19, and respiratory syndrome coronavirus 2 (SARS-CoV-2) infection) and 33 different types of cancers of the European population. The results of the inverse-variance-weighted model indicated that genetic liabilities to critically ill COVID-19 had suggestive causal associations with the increased risk for HER2-positive breast cancer (odds ratio [OR] = 1.0924; p-value = 0.0116), esophageal cancer (OR = 1.0004; p-value = 0.0226), colorectal cancer (OR = 1.0010; p-value = 0.0242), stomach cancer (OR = 1.2394; p-value = 0.0331), and colon cancer (OR = 1.0006; p-value = 0.0453). The genetic liabilities to hospitalized COVID-19 had suggestive causal associations with the increased risk for HER2-positive breast cancer (OR = 1.1096; p-value = 0.0458), esophageal cancer (OR = 1.0005; p-value = 0.0440) as well as stomach cancer (OR = 1.3043; p-value = 0.0476). The genetic liabilities to SARS-CoV-2 infection had suggestive causal associations with the increased risk for stomach cancer (OR = 2.8563; p-value = 0.0019) but with the decreasing risk for head and neck cancer (OR = 0.9986, p-value = 0.0426). The causal associations of the above combinations were robust through the test of heterogeneity and pleiotropy. Together, our study indicated that COVID-19 had causal effects on cancer risk.

Effects of land clearing for agriculture on soil organic carbon stocks in drylands: A meta-analysis.

Agricultural activities have been expanding globally with the pressure to provide food security to the earth's growing population. These agricultural activities have profoundly impacted soil organic carbon (SOC) stocks in global drylands. However, the effects of clearing natural ecosystems for cropland (CNEC) on SOC are uncertain. To improve our understanding of carbon emissions and sequestration under different land uses, it is necessary to characterize the response patterns of SOC stocks to different types of CNEC. We conducted a meta-analysis with mixed-effect model based on 873 paired observations of SOC in croplands and adjacent natural ecosystems from 159 individual studies in global drylands. Our results indicate that CNEC significantly (p < .05) affects SOC stocks, resulting from a combination of natural land clearing, cropland management practices (fertilizer application, crop species, cultivation duration) and the significant negative effects of initial SOC stocks. Increases in SOC stocks (in 1 m depth) were found in croplands which previously natural land (deserts and shrublands) had low SOC stocks, and the increases were 278.86% (95% confidence interval, 196.43%-361.29%) and 45.38% (26.53%-62.23%), respectively. In contrast, SOC stocks (in 1 m depth) decreased by 24.11% (18.38%-29.85%) and 10.70% (1.80%-19.59%) in clearing forests and grasslands for cropland, respectively. We also established the general response curves of SOC stocks change to increasing cultivation duration, which is crucial for accurately estimating regional carbon dynamics following CNEC. SOC stocks increased significantly (p < .05) with high long-term fertilizer consumption in cleared grasslands with low initial SOC stocks (about 27.2 Mg ha-1 ). The results derived from our meta-analysis could be used for refining the estimation of dryland carbon dynamics and developing SOC sequestration strategies to achieve the removal of CO2 from the atmosphere.

Income-related equity in inpatient care utilization and unmet needs between 2013 and 2018 in Tibet, China.

BACKGROUND: Providing equitable access to health care for all populations is an important sustainable development goal. China has made significant progress in achieving equity in healthcare utilization. However, research on equity in healthcare utilization in Tibet is sparse. This study aims to evaluate changes in income-related inequity in inpatient care utilization and unmet needs between 2013 and 2018 among the Tibetan population and identify the inequity source. METHODS: Data for this cross-sectional study were obtained from the fifth and sixth waves of the National Health Services Survey in 2013 and 2018. After excluding observations with missing values for key variables, 11,092 and 10,397 respondents were included in this study, respectively. The outcome variables of interest were inpatient service utilization and unmet hospitalization needs. The concentration index and horizontal inequity index (HI) were used to assess income-related inequity. Non-linear decompositions were performed to identify the main contributors to inequity. In the decomposition method, need variables included sex, age, chronic diseases, and the EuroQol-Visual Analog Scale; non-need variables consisted of income, education, employment status, marital status, and health insurance schemes. RESULTS: The probability of inpatient care utilization increased from 6.40% in 2013 to 8.50% in 2018. The HI for inpatient care utilization was 0.19 (P < 0.001) in 2013, whereas it decreased to 0.07 (P < 0.001) in 2018. The contribution of income to inequity in inpatient care utilization decreased from 87.09% in 2013 to 59.79% in 2018. As for unmet inpatient care needs, although its probability increased from 0.76 to 1.48%, the percentage of reasons for financial hardship decreased from 47.62 to 28.57%. The HI for unmet hospitalization need was - 0.07 in 2013 and - 0.05 in 2018, and neither was statistically significant. The New Rural Cooperative Medical Scheme made majority contributions to promote equity in unmet hospitalization need. Moreover, the female respondents reporting low EuroQol-Visual Analog Scale scores and patients with chronic disease were not only more likely to seek for inpatient care, but also have more unmet need than the reference groups. CONCLUSIONS: The inequity in inpatient care utilization in Tibet narrowed from 2013 to 2018, and there was no inequity in unmet hospitalization needs in 2013 and 2018. Income and the New Rural Cooperative Medical Scheme are the main drivers of equity promotion. To promote access to inpatient care utilization and decrease the probability of unmet hospitalization need in future, policymakers should target high-need residents in Tibet to improve accessibility, availability, and acceptability.

Mapping the Seattle Angina Questionnaire to EQ-5D-5L in patients with coronary heart disease.

BACKGROUND: Health economic evaluation is critical in supporting novel cardiovascular disease therapies. However, most clinical studies do not include preference-based questionnaires to calculate utilities for health economic evaluations. Thus, this study aimed to develop mapping algorithms that convert the Seattle Angina Questionnaire (SAQ) to EQ-5D-5L health utility scores for patients with coronary health disease (CHD) in China. METHODS: Data were obtained from a longitudinal study of patients with CHD conducted at the Tianjin Medical University General Hospital in China. Convenience sampling was used to recruit patients with CHD. The inclusion criteria were having been diagnosed with CHD through a medical examination and being aged 18 years or older. The exclusion criteria were a lack of comprehension ability, serious comorbidities, mental illness, and hearing or vision impairment. All eligible patients were invited to participate, and 305 and 75 patients participated at baseline and in the follow-up, respectively. Seven regression models were developed using a direct approach. Furthermore, we predicted the five EQ-5D items using ordered logit model and derived the utility score from predicted responses using an indirect approach. Model performances were evaluated using mean absolute error (MAE), root mean squared error (RMSE), correlation coefficient (ρ), and Lin's concordance correlation coefficient (CCC). A five-fold cross-validation method was used to evaluate internal validation. RESULTS: The average age was 63.04 years, and 53.72% of the included patients were male. Most (70.05%) patients had unstable angina pectoris, and the mean illness duration was 2.50 years. The EQ-5D scores were highly correlated with five subscales of the SAQ, with Spearman's rank correlation coefficients ranging from 0.6184 to 0.7093. The mixture beta model outperformed the other regression models in the direct approach, with the lowest MAE and RMSE and highest ρ and CCC. The ordered logit model in the indirect approach performed the same as the mixture beta regression with equal MAE, lower RMSE, and higher ρ and CCC. CONCLUSION: Mapping algorithms developed using mixture beta and ordered logit models accurately converted SAQ scores to EQ-5D-5L health utility values, which could support health economic evaluations related to coronary heart disease.

Nonadiabatic heavy atom tunneling in 1nσ*-mediated photodissociation of thioanisole.

The 1nσ*-mediated photodissociation dynamics of thioanisole is investigated quantum mechanically using a three-dimensional model based on a newly constructed diabatic potential energy matrix. The lifetimes of the low-lying S1(1ππ*) resonances are determined and found to accord well with available experimental data. Specifically, our theoretical results demonstrate that the photodissociation of thioanisole at the low-lying S1(1ππ*) levels takes place via the heavy atom tunneling due to the higher S1/S2 conical intersection and two equivalent out-of-plane saddle points appearing on the dissociation path. The isotopic effect on the lifetimes is found to be pronounced, manifesting the nature of the tunneling process. Moreover, the geometric phase effect around the S1/S2 conical intersection is found to slightly impact the lifetimes due to the weak destructive or constructive interferences in this heavy atom tunneling, which differs significantly from the scenario in the nonadiabatic hydrogen atom tunneling. Importantly, the quantum mechanical treatment is essentially required to accurately describe the 1nσ*-mediated photodissociation dynamics of thioanisole owing to involving quantum tunneling and geometric phase effects near the conical intersection.

Hidden Markov Modeling Reveals Prolonged "Baseline" State and Shortened Antagonistic State across the Adult Lifespan.

The brain networks undergo functional reorganization across the whole lifespan, but the dynamic patterns behind the reorganization remain largely unclear. This study models the dynamics of spontaneous activity of large-scale networks using hidden Markov model (HMM), and investigates how it changes with age on two adult lifespan datasets of 176/157 subjects (aged 20-80 years). Results for both datasets showed that 1) older adults tended to spend less time on a state where default mode network (DMN) and attentional networks show antagonistic activity, 2) older adults spent more time on a "baseline" state with moderate-level activation of all networks, accompanied with lower transition probabilities from this state to the others and higher transition probabilities from the others to this state, and 3) HMM exhibited higher sensitivity in uncovering the age effects compared with temporal clustering method. Our results suggest that the aging brain is characterized by the shortening of the antagonistic instances between DMN and attention systems, as well as the prolongation of the inactive period of all networks, which might reflect the shift of the dynamical working point near criticality in older adults.

Clinical characteristics and prognosis of patients with idiopathic membranous nephropathy with kidney tubulointerstitial damage.

BACKGROUND: To investigate the clinical and kidney pathological features and prognosis of idiopathic membranous nephropathy (IMN) with kidney tubulointerstitial damage (TID). METHODS: Based on the presence or absence of kidney TID by kidney biopsy, 300 patients diagnosed with IMN were categorized into non-TID (TID-) and tubulointerstitial injury (TID+) groups. The clinical and pathological data were analyzed retrospectively. All patients were followed up for 6-24 months after treatment with glucocorticoids (GCs) combined with cyclophosphamide or GCs combined with calcineurin inhibitors (CNIs) to observe treatment effects on patient prognosis. RESULTS: The patients in the TID + group were older and more likely to be male. The 24-h urine protein, blood urea nitrogen, serum creatinine, cystatin C, ß2-microglobulin, and antiphospholipase A2 receptor antibody levels were higher than those in the TID - group and the pathological manifestations were more severe. After 1 year of follow-up, the overall response rate (complete response + partial response) in the TID + group was lower (66.67% vs. 80.89%, p = .022) than in the other. After combined GC and CNI therapy, the complete remission rate in the TID + group was significantly lower than that in the TID - group (13.79% vs. 35.46%, p = .022). The 24-h urine protein level was an independent risk factor for worsening kidney condition (p = .038). CONCLUSION: Patients with IMN with TID have more severe clinical manifestations and pathological damage and lower remission rates. IMN with TID is a risk factor for worsening kidney condition; however, it is not an independent risk factor.

Human Umbilical Vein Endothelial Cells Survive on the Ischemic TCA Cycle under Lethal Ischemic Conditions.

It is generally believed that vascular endothelial cells (VECs) rely on glycolysis instead of the tricarboxylic acid (TCA) cycle under both normoxic and hypoxic conditions. However, the metabolic pattern of human umbilical vein endothelial cells (HUVECs) under extreme ischemia (hypoxia and nutrient deprivation) needs to be elucidated. We initiated a lethal ischemic model of HUVECs, performed proteomics and bioinformatics, and verified the metabolic pattern shift of HUVECs. Ischemic HUVECs displayed extensive aerobic respiration, including upregulation of the TCA cycle and mitochondrial respiratory chain in mitochondria and downregulation of glycolysis in cytoplasm. The TCA cycle was enhanced while the cell viability was decreased through the citrate synthase pathway when substrates of the TCA cycle (acetate and/or pyruvate) were added and vice versa when inhibitors of the TCA cycle (palmitoyl-CoA and/or avidin) were applied. The inconsistency of the TCA cycle level and cell viability suggested that the extensive TCA cycle can keep cells alive yet generate toxic substances that reduce cell viability. The data revealed that HUVECs depend on "ischemic TCA cycle" instead of glycolysis to keep cells alive under lethal ischemic conditions, but consideration must be given to relieve cell injury.

Phase Conversion Accelerating "Zn-Escape" Effect in ZnSe-CFs Heterostructure for High Performance Sodium-Ion Half/Full Batteries.

Sodium-ion batteries (SIBs) are considered as a promising large-scale energy storage system owing to the abundant and low-cost sodium resources. However, their practical application still needs to overcome some problems like slow redox kinetics and poor capacity retention rate. Here, a high-performance ZnSe/carbon fibers (ZnSe-CFs) anode is demonstrated with high electrons/Na+ transport efficiency for sodium-ion half/full batteries by engineering ZnSe/C heterostructure. The electrochemical behavior of the ZnSe-CFs heterostructure anode is deeply studied via in situ characterizations and theoretical calculations. Phase conversion is revealed to accelerate the "Zn-escape" effect for the formation of robust solid electrolyte interphase (SEI). This leads to the ZnSe-CFs delivering a superior rate performance of 206 mAh g-1 at 1500 mA g-1 for half battery and an initial discharge capacity of 197.4 mAh g-1 at a current density of 1 A g-1 for full battery. The work here heralds a promising strategy to synthesize advanced heterostructured anodes for SIBs, and provides the guidance for a better understanding of phase conversion anodes.