Regulation of urea cycle by reversible high-stoichiometry lysine succinylation.

The post-translational modification lysine succinylation is implicated in the regulation of various metabolic pathways. However, its biological relevance remains uncertain due to methodological difficulties in determining high-impact succinylation sites. Here, using stable isotope labelling and data-independent acquisition mass spectrometry, we quantified lysine succinylation stoichiometries in mouse livers. Despite the low overall stoichiometry of lysine succinylation, several high-stoichiometry sites were identified, especially upon deletion of the desuccinylase SIRT5. In particular, multiple high-stoichiometry lysine sites identified in argininosuccinate synthase (ASS1), a key enzyme in the urea cycle, are regulated by SIRT5. Mutation of the high-stoichiometry lysine in ASS1 to succinyl-mimetic glutamic acid significantly decreased its enzymatic activity. Metabolomics profiling confirms that SIRT5 deficiency decreases urea cycle activity in liver. Importantly, SIRT5 deficiency compromises ammonia tolerance, which can be reversed by the overexpression of wild-type, but not succinyl-mimetic, ASS1. Therefore, lysine succinylation is functionally important in ammonia metabolism.

Neuroprotective effects of Shenghui decoction via inhibition of the JNK/p38 MAPK signaling pathway in an AlCl3-induced zebrafish (Danio rerio) model of Alzheimer's disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) is a multi-factorial degenerative disease, and multi-targeted therapies targeting multiple pathogenic mechanisms should be explored. Shenghui decoction (SHD) is an ancient traditional Chinese medicine (TCM) formula used clinically to alleviate AD. However, the precise mechanism of action of SHD as a therapeutic agent for AD remains unclear. AIM OF THE STUDY: This study investigated the neuroprotective properties and potential mechanisms of action of SHD in mitigating AD-like symptoms induced by AlCl3 in a zebrafish model. MATERIALS AND METHODS: Active components of SHD were detected using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Zebrafish were exposed to AlCl3 (200 µg/L) for 30 days to establish an AD zebrafish model. AlCl3-exposed zebrafish were treated with SHD or donepezil. Behavioral tests were used to assess learning and memory, locomotor activity, and AD-related anxiety and aggression in AlCl3-exposed zebrafish. Nissl staining and transmission electron microscopy were used to evaluate histological alterations in brain neurons. The concentrations of pro-inflammatory cytokines (tumor necrosis factor-α, TNF-α; interleukin-1ß, IL-1ß) were quantified using Enzyme-linked immunosorbent assay (ELISA). Markers of oxidative stress and cholinergic activity (acetylcholinesterase, AChE) were detected using biochemical assays. Western blotting and immunofluorescence were used to detect the protein expression levels of Aß, p-tau, PSD-95, synaptophysin, TLR4, phosphorylation of NF-κB p65, p38, and JNK. RESULTS: Fifteen SHD compounds were identified by UPLC-MS/MS analysis. SHD improved AlCl3-induced dyskinesia, learning and memory impairment, anxiety-like behavior, and aggressive behavior in zebrafish. AlCl3-exposed zebrafish showed AD-like pathology, overexpression of Aß, hyperphosphorylated tau protein, marked neuronal damage, decreased expression of synaptic proteins, synaptophysin, and PSD-95, and impairment of synaptic structural plasticity. These effects were reversed by the SHD treatment. We also observed that SHD ameliorated oxidative stress and decreased AChE activity and inflammatory cytokine levels. These effects are similar to those observed for donepezil. Meanwhile, SHD could decrease the protein expression of TLR4 and inhibit phosphorylation of NF-κB, JNK, and p38 MAPK. These results demonstrate that SHD has the potential to exert neuroprotective effects, which may be partly mediated via inhibition of the JNK/p38 MAPK signaling pathway. CONCLUSIONS: Our findings revealed the therapeutic mechanism of SHD in mitigating AD progression and suggested that SHD is a potent neuroprotectant that contributes to the future development of TCM modernization and broader clinical applications.

Promoting high-voltage stability through local lattice distortion of halide solid electrolytes.

Stable solid electrolytes are essential to high-safety and high-energy-density lithium batteries, especially for applications with high-voltage cathodes. In such conditions, solid electrolytes may experience severe oxidation, decomposition, and deactivation during charging at high voltages, leading to inadequate cycling performance and even cell failure. Here, we address the high-voltage limitation of halide solid electrolytes by introducing local lattice distortion to confine the distribution of Cl-, which effectively curbs kinetics of their oxidation. The confinement is realized by substituting In with multiple elements in Li3InCl6 to give a high-entropy Li2.75Y0.16Er0.16Yb0.16In0.25Zr0.25Cl6. Meanwhile, the lattice distortion promotes longer Li-Cl bonds, facilitating favorable activation of Li+. Our results show that this high-entropy halide electrolyte boosts the cycle stability of all-solid-state battery by 250% improvement over 500 cycles. In particular, the cell provides a higher discharge capacity of 185 mAh g-1 by increasing the charge cut-off voltage to 4.6 V at a small current rate of 0.2 C, which is more challenging to electrolytes|cathode stability. These findings deepen our understanding of high-entropy materials, advancing their use in energy-related applications.

Photoaffinity labeling coupled with proteomics identify PDI-ADAM17 module is targeted by (-)-vinigrol to induce TNFR1 shedding and ameliorate rheumatoid arthritis in mice.

Various biological agents have been developed to target tumor necrosis factor alpha (TNF-α) and its receptor TNFR1 for the rheumatoid arthritis (RA) treatment, whereas small molecules modulating such cytokine receptors are rarely reported in comparison to the biologicals. Here, by revealing the mechanism of action of vinigrol, a diterpenoid natural product, we show that inhibition of the protein disulfide isomerase (PDI, PDIA1) by small molecules activates A disintegrin and metalloprotease 17 (ADAM17) and then leads to the TNFR1 shedding on mouse and human cell membranes. This small-molecule-induced receptor shedding not only effectively blocks the inflammatory response caused by TNF-α in cells, but also reduces the arthritic score and joint damage in the collagen-induced arthritis mouse model. Our study indicates that targeting the PDI-ADAM17 signaling module to regulate the shedding of cytokine receptors by the chemical approach constitutes a promising strategy for alleviating RA.

Loss of ACTL7A causes small head sperm by defective acrosome-acroplaxome-manchette complex.

BACKGROUND: Actin-like 7 A (ACTL7A) is essential for acrosome formation, fertilization and early embryo development. ACTL7A variants cause acrosome detachment responsible for male infertility and early embryonic arrest. In this study, we aim to explore the additional functions of ACTL7A beyond the process of acrosome biogenesis and investigate the possible underlying mechanisms. METHODS: Nuclear morphology analysis was used to observe the sperm head shape of ACTL7A-mutated patients. Actl7a knock-out (KO) mouse model was generated. Immunofluorescence and transmission electron microscopy (TEM) were performed to analyze the structure of spermatids during spermiogenesis. Tandem mass tags labeling quantitative proteomics strategy was employed to explore the underlying molecular mechanisms. The expression levels of key proteins in the pathway were analyzed by western blotting. Intracytoplasmic sperm injection (ICSI)-artificial oocyte activation (AOA) technology was utilized to overcome fertilization failure in male mice with a complete knockout of Actl7a. RESULTS: The new phenotype of small head sperm associated with loss of ACTL7A in patients was discovered, and further confirmed in Actl7a-KO mice. Immunofluorescence and TEM analyses revealed that the deletion of ACTL7A damaged the formation of acrosome-acroplaxome-manchette complex, leading to abnormalities in the shaping of sperm heads. Moreover, a proteomic analysis of testes from WT and Actl7a-KO mice revealed that differentially expressed genes were notably enriched in PI3K/AKT/mTOR signaling pathway which is strongly associated with autophagy. Inhibition of autophagy via PI3K/AKT/mTOR signaling pathway activation leading to PDLIM1 accumulation might elucidate the hindered development of manchette in Actl7a-KO mice. Remarkably, AOA successfully overcame fertilization failure and allowed for the successful production of healthy offspring from the Actl7a complete knockout male mice. CONCLUSIONS: Loss of ACTL7A causes small head sperm as a result of defective acrosome-acroplaxome-manchette complex via autophagy inhibition. ICSI-AOA is an effective technique to rescue male infertility resulting from ACTL7A deletion. These findings provide essential evidence for the diagnosis and treatment of patients suffering from infertility.

Mediating role of learned helplessness' components in the association between health literacy/social support and self-management among maintenance haemodialysis patients in Changsha, China: a cross-sectional study.

OBJECTIVES: To explore the multiple mediating roles of the learned helplessness's core system in the relationship between health literacy/social support and self-management. DESIGN: Cross-sectional survey design. SETTING: Changsha, China. PARTICIPANTS: 239 Chinese maintenance haemodialysis (MHD) patients. METHODS: Two multiple mediator models were constructed based on the COM-B (Capacity, Opportunity, Motivation - Behaviour) model. A total of 239 Chinese MHD patients participated in a cross-sectional study, which included surveys on the Learned Helplessness Scale for MHD patients, Dialysis Knowledge Questionnaire, Social Support Scale and Self-Management Scale for Haemodialysis. The PROCESS macro in SPSS was used for mediated effects analysis. RESULTS: Helplessness and internality partially mediated the relationship between health literacy/social support and self-management ((ß=-0.212, p<0.01; ß=0.240, p<0.01)/(ß=-0.331, p<0.001; ß=0.376, p<0.001)). The mediation effect size was 0.780 (95% CI (0.373 to 1.218)) in the health literacy model, accounting for 45.29% of the total effect, and 0.286 (95% CI (0.207 to 0.377)) in the social support model, accounting for 57.88% of the total effect. The differences in effect sizes for helplessness and internality in the two models were -0.080 (95% CI (-0.374 to 0.216)) and -0.041 (95% CI (-0.127 to 0.043)), respectively. CONCLUSION: Health literacy/social support directly affects MHD patients' self-management and indirectly affects it by changing learned helplessness, such as increasing internality while reducing helplessness.

Case Report: A rare synchronous multiple gastric carcinoma achieved progression-free disease through NGS-guided serial treatment.

Synchronous multiple gastric carcinoma (SMGC) is a rare condition characterized by the simultaneous occurrence of two or more primary malignant tumors in the stomach, each with its own distinct pathological morphology. SMGC differs from gastric metastases, which originate from primary gastric or non-gastric tumors. At present, the incidence of SMGC is low in China, with no established guidelines for standard treatment. Here, we report a rare case of advanced SMGC that achieved long-lasting clinical benefits through a treatment strategy informed by next-generation sequencing (NGS). Dynamically monitoring of the tumor and/or circulating cell-free DNA guided the patient's treatment sequentially. The patient received anti-HER2 therapy, followed by immunotherapy, pembrolizumab in combination with trastuzumab and chemotherapy, and ultimately underwent successful total gastrectomy. This case highlights a novel approach of utilizing liquid biopsy-based NGS to gain insights into disease progression and molecular response to NGS-guided treatment in SMGC patients.

Ginsenoside Rg1 alleviates sleep deprivation-induced learning and memory impairment by inhibiting excessive neuronal apoptosis in zebrafish.

Sleep deprivation impairs learning and memory. The neuroprotective function of ginsenoside Rg1 (Rg1) has been reported. This study aimed to investigate the alleviative effect and underlying mechanism of action of Rg1 on learning and memory deficits induced by sleep deprivation. Using 72 h of LED light to establish sleep deprivation model and treatment with Rg1-L (0.5 mg/ml), Rg1-H (1 mg/ml), and melatonin (positive control, 0.25 mg/ml), we investigated the behavioral performance of sleep deprivation zebrafish through 24 h autonomous movement tracking, a novel tank diving test, and a T-maze test. Brain injuries and ultrastructural changes were observed, brain water content was measured, and apoptotic events were analyzed using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining. The oxidation-associated biomarkers superoxide dismutase, catalase, and glutathione peroxidase activity and lipid peroxidation product malondialdehyde content were detected. Real-time PCR and western blotting were performed to detect the levels of apoptotic molecules (Bax, caspase-3, and Bcl-2). Rg1-treatment was observed to improve the behavioral performance of sleep-deprivation fish, alleviate brain impairment, and increase oxidative stress-related enzyme activity. Rg1 can effectively exhibit neuroprotective functions and improve learning and memory impairments caused by sleep deprivation, which could be mediated by the Bcl-2/Bax/caspase-3 apoptotic signaling pathway (see Supplementary Video Abstract, Supplemental digital content, http://links.lww.com/WNR/A702 which demonstrates our research objectives, introduction overview of Rg1, and main direction of future research).

Radiomics model based on intravoxel incoherent motion and diffusion kurtosis imaging for predicting histopathological grade and Ki-67 expression level of soft tissue sarcomas.

BACKGROUND: Accurate identification of the histopathological grade and the Ki-67 expression level is important in clinical cases of soft tissue sarcomas (STSs). PURPOSE: To explore the feasibility of a radiomics model based on intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) and diffusion kurtosis imaging (DKI) MRI parameter maps in predicting the histopathological grade and Ki-67 expression level of STSs. MATERIAL AND METHODS: In total, 42 patients diagnosed with STSs between May 2018 and January 2020 were selected. The MADC software in Functool of GE ADW 4.7 workstation was used to obtain standard apparent diffusion coefficient (ADC), D, D*, f, mean diffusivity, and mean kurtosis (MK). The histopathological grade and Ki-67 expression level of STSs were identified. The radiomics features of IVIM and DKI parameter maps were used as the dataset. The area under the receiver operating characteristic curve (AUC) and F1-score were calculated. RESULTS: D-SVM achieved the best diagnostic performance for histopathological grade. The AUC in the validation cohort was 0.88 (sensitivity: 0.75 [low level] and 0.83 [high level]; specificity: 0.83 [low level] and 0.75 [high level]; F1-score: 0.75 [low level] and 0.83 [high level]). MK-SVM achieved the best diagnostic performance for Ki-67 expression level. The AUC in the validation cohort was 0.83 (sensitivity: 0.83 [low level] and 0.50 [high level; specificity: 0.50 [low level] and 0.83 [high level]; F1-score: 0.77 [low level] and 0.57 [high level]). CONCLUSION: The proposed radiomics classifier could predict the pathological grade of STSs and the Ki-67 expression level in STSs.

SARS-CoV-2 protein ORF8 limits expression levels of Spike antigen and facilitates immune evasion of infected host cells.

Recovery from COVID-19 depends on the ability of the host to effectively neutralize virions and infected cells, a process largely driven by antibody-mediated immunity. However, with the newly emerging variants that evade Spike-targeting antibodies, re-infections and breakthrough infections are increasingly common. A full characterization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mechanisms counteracting antibody-mediated immunity is therefore needed. Here, we report that ORF8 is a virally encoded SARS-CoV-2 factor that controls cellular Spike antigen levels. We show that ORF8 limits the availability of mature Spike by inhibiting host protein synthesis and retaining Spike at the endoplasmic reticulum, reducing cell-surface Spike levels and recognition by anti-SARS-CoV-2 antibodies. In conditions of limited Spike availability, we found ORF8 restricts Spike incorporation during viral assembly, reducing Spike levels in virions. Cell entry of these virions then leaves fewer Spike molecules at the cell surface, limiting antibody recognition of infected cells. Based on these findings, we propose that SARS-CoV-2 variants may adopt an ORF8-dependent strategy that facilitates immune evasion of infected cells for extended viral production.

Effect of Vitamin D Supplementation on Clinical Course and T Helper 17/ T-Regulatory Balance in Peripheral Blood of Patients with Crohn's Disease.

BACKGROUND: Vitamin D has anti-inflammatory properties and is involved in immune function, making it a potential therapy for Crohn's disease. This study aimed to investigate the effects of vitamin D supplementation on immune function and the clinical efficacy of patients with Crohn's disease. METHODS: From September 2017 to September 2021, patients with Crohn's disease were recruited and randomly divided into 2 groups: the routine treatment group (n = 52) and the vitamin D supplement group (n = 50). In addition to routine treatment, the vitamin D group received oral calcitriol capsule supplementation, while the routine treatment group did not receive any additional intervention. T helper 17/T-regulatory cell level, inflammatory indicators, and nutritional status were compared between the 2 groups, as well as mucosal healing under endoscopy and the life quality of patients. RESULTS: C-reactive protein was significantly lower in the vitamin D treatment group compared to the routine treatment group (6.08 ± 2.72 vs. 18.91 ± 2.66, P < .05). Compared to the routine treatment group, the ratio of T helper 17/T-regulatory cells was significantly lower in the vitamin D group (0.26 ± 0.12 vs. 0.55 ± 0.11, P < .05). After vitamin D treatment, both of the average Crohn's disease activity index score (from 319.7 ± 72.7 to 179.6 ± 48.5, P < .05) and simple endoscopic score for Crohn's disease score (from 7.9 ± 2.3 to 3.9 ± 0.6, P < .05) were significantly decreased, while the Inflammatory Bowel Disease Questionnaire score was significantly increased (from 137.8 ± 21.2 to 158.1 ± 25.1, P < .05). CONCLUSIONS: Vitamin D has the potential to improve the inflammatory status and immune environment of patients with Crohn's disease, which can reduce the level of inflammatory factors and help the recovery of symptoms, thus improving the clinical course and quality of life in Crohn's disease patients.

Association of serum water-soluble vitamin exposures with the risk of metabolic syndrome: results from NHANES 2003-2006.

Introduction: Existing evidence suggests an association between certain vitamins and metabolic syndrome (MetS), but few epidemiological studies have focused on the effects of multivitamin co-exposure on MetS. This study aims to investigate the associations of the individual or multiple water-soluble vitamins (i.e., vitamin C (VC), vitamin B9 (VB9), and vitamin B12 (VB12)) with co-exposure to MetS, as well as the dose-response relationships among them. Methods: A cross-sectional study was conducted by employing the National Health and Examination Surveys (NHANESs) 2003-2006. Multivariate-adjusted logistic regression models were used to explore the association between individual serum water-soluble vitamins and the risk of MetS and its components, including waist circumference, triglyceride, high-density lipoprotein, blood pressure, and fasting plasma glucose. Restricted cubic splines were performed to explore the dose-response relationships among them. The quantile g-computation method was adopted to explore the associations of multiple water-soluble vitamins co-exposure with MetS risk and MetS components. Results: A total of 8983 subjects were involved in the study, of whom 1443 were diagnosed with MetS. The MetS groups had a higher proportion of participants with age ≥60 years, BMI ≥30 kg/m2, and insufficient physical activity. Compared with the lowest quartile, the third (OR=0.67, 95% CI: 0.48, 0.94) and highest quartiles (OR=0.52, 95%CI: 0.35, 0.76) of VC were associated with lower MetS risk. Restricted cubic splines showed negative dose-response relationships among VC, VB9 and VB12, and MetS. Regarding MetS components, higher VC quartiles were associated with lower waist circumference, triglyceride, blood pressure, and fasting plasma glucose, while higher VC and VB9 quartiles were associated with higher high-density lipoprotein (HDL). Co-exposure to VC, VB9, and VB12 was significantly inversely associated with MetS, with ORs (95% CI) of 0.81 (0.74, 0.89) and 0.84 (0.78, 0.90) in the conditional and marginal structural models, respectively. Furthermore, we found that VC, VB9, and VB12 co-exposure were negatively associated with waist circumference and blood pressure, while VC, VB9, and VB12 co-exposure were positively associated with HDL. Conclusion: This study revealed negative associations of VC, VB9, and VB12 with MetS, while the high water-soluble vitamin co-exposure was associated with a lower MetS risk.

Antibacterial Activity of Epigallocatechin Gallate (EGCG) against Shigella flexneri.

Shigella flexneri (S. flexneri), a major intestinal pathogen, is a global public health concern. The biofilms formed by S. flexneri threaten environmental safety, since they could promote the danger of environmental contamination and strengthen the disease-causing properties of bacteria. Epigallocatechin gallate (EGCG) is an important catechin in tea, which has a high antibacterial activity. However, its antibacterial mechanism is still unclear. This research aims to quantify the antibacterial function and investigate the possible mechanism of EGCG inhibition of S. flexneri. The minimum inhibitory concentration (MIC) of EGCG against planktonic S. flexneri in the investigation was measured to be 400 µg/mL. Besides, SDS-PAGE and field emission scanning electron microscopy showed that EGCG interfered with protein synthesis and changed bacteria morphology. Through controlling the expression of the mdoH gene, EGCG was found to be able to prevent an S. flexneri biofilm extracellular polysaccharide from forming, according to experiments utilizing the real-time PCR test. Additional research revealed that EGCG might stimulate the response of S. flexneri to oxidative stress and prevent bacterial growth. These findings suggest that EGCG, a natural compound, may play a substantial role in S. flexneri growth inhibition.

Does smooth endoplasmic reticulum aggregation in oocytes impact the chromosome aneuploidy of the subsequent embryos? A propensity score matching study.

BACKGROUND: The appearance of smooth endoplasmic reticulum aggregation (SERa) is one of the most common dysmorphic phenotypes of oocytes, however, the impact of SERa occurrence on in vitro fertilization (IVF) outcomes is controversial. This study aimed to investigate the impact of SERa in oocytes on the aneuploidy of the subsequent embryos in IVF. METHODS: In this retrospective cohort study, a total of 114 intracytoplasmic sperm injection (ICSI) cycles with the appearance of SERa undergoing preimplantation genetic testing for aneuploidy (PGT-A) were enrolled, and among them there were 323 SERa(+) oocytes and 1253 sibling unaffected oocytes. The 907 PGT-A cycles without SERa during the same period were enrolled as controls. A propensity score matching of 1:1 ratio between these two groups resulted in 113 matched cycles. The outcome parameters between the SERa(+) cycles/oocytes and the controls were compared. IVF laboratory outcomes, PGT-A outcomes, and clinical and neonatal outcomes were the main outcomes. RESULTS: Increased abnormal fertilization rate and reduced blastocyst formation rate can be observed in both SERa(+) cycles and oocytes, some other parameters on developmental potential, such as available embryo rate at Day 3 and available blastocyst rate, were also impaired in the case of SERa occurrences. Among the 910 blastocysts for PGT-A, the percentage of euploid embryos was similar between the matched cohorts, while an unpredicted increase of the proportions of euploid in the SERa(+) oocytes, compared to the SERa(-) oocytes. Moreover, there was no significance in terms of clinical and neonatal outcomes, such as implantation rate, biochemical pregnancy rate, clinical pregnancy rate, miscarriage rate, and live birth rate, regardless of the presence of SERa in cycles and oocytes. CONCLUSIONS: The appearance of SERa within mature oocytes has no significant impact on the aneuploidy of subsequent blastocysts. It is recommended to utilize these oocytes, especially for those with few oocytes or advanced maternal age, which is likely to increase the cumulative pregnancy rate. This study may offer evidence to assist embryologists to make clinical decisions concerning SERa(+) oocytes more consciously and rationally.

Genetic analysis and elite tree selection of the main resin components of slash pine.

Pine resin, as a natural material, has been widely used in food, pharmaceutical, and chemical industries. Slash pine (Pinus elliottii Engelm var. elliottii) is the primary tree species for resin tapping due to its high resin yield, low resin crystallization rate, and high turpentine content. Current researches focuse on the targeted improvement of several significant components to meet industrial needs rather than just resin yield. The objective of this study was to examine the genetic variation and correlation of genetic and phenotype for four main resin components (α pinene, ß pinene, abietic acid, and levoprimaric acid) of 219 half-sib progenies from 59 families. The results showed that the levopimaric acid had the largest content (mean value = 21.63%), while the ß pinene content had the largest variation coefficient (CV = 0.42). The α pinene content has the highest heritability (h2 = 0.67), while levopimaric acid has the lowest heritability (h2 = 0.51). There was a significant negative correlation between α pinene and the other three components and a significant positive correlation between ß pinene and the two diterpenes. The family ranking and genetic gain suggested that it is possible to improve the contents of main resin components of slash pine through genetic breeding selection.

The Relationship between the Transmission of Different SARS-CoV-2 Strains and Air Quality: A Case Study in China.

Coronavirus Disease 2019 (COVID-19) has been a global public health concern for almost three years, and the transmission characteristics vary among different virus variants. Previous studies have investigated the relationship between air pollutants and COVID-19 infection caused by the original strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, it is unclear whether individuals might be more susceptible to COVID-19 due to exposure to air pollutants, with the SARS-CoV-2 mutating faster and faster. This study aimed to explore the relationship between air pollutants and COVID-19 infection caused by three major SARS-CoV-2 strains (the original strain, Delta variant, and Omicron variant) in China. A generalized additive model was applied to investigate the associations of COVID-19 infection with six air pollutants (PM2.5, PM10, SO2, CO, NO2, and O3). A positive correlation might be indicated between air pollutants (PM2.5, PM10, and NO2) and confirmed cases of COVID-19 caused by different SARS-CoV-2 strains. It also suggested that the mutant variants appear to be more closely associated with air pollutants than the original strain. This study could provide valuable insight into control strategies that limit the concentration of air pollutants at lower levels and would better control the spread of COVID-19 even as the virus continues to mutate.

The cross-cultural adaptation and psychometric evaluation of a learned helplessness scale for maintenance hemodialysis patients in China (LHS-MHD-C).

Learned helplessness (LH) is an important concept in nursing. This study aimed to adapt and translate the Arthritis Helplessness Index scale into a Chinese version of an LH scale for maintenance hemodialysis patients in China (LHS-MHD-C), and to validate its psychometric properties. Data collected included LHS-MHD-C, as well as the Hospital Depression Scale (HADS-D), and the Beck Hopelessness Scale (BHS) for assessing LHS-MHD-C's criterion validity (predictive and concurrent, respectively). The expert consultation and the pilot study demonstrated semantic and conceptual equivalence and content validity (except for Item 3, the item content validity ranged from 0.82 to 1, and the scale content validity was 0.95). An exploratory factor analysis (n = 146) eliminated three items and accepted 11 items for the two factors, explaining 63.87% of the total variance. A CFA (n = 218) showed that the two-factors structure was consistent with the LH theory. The LHS-MHD-C can distinguish between maintenance hemodialysis (MHD) patients of different ages, education, working status, monthly income, and MHD duration. The scale had good concurrent validity with the BHS (r = .78, p < 0.01). Using the HADS-D as a criterion, the LHS-MHD-C showed a sensitivity of 86.2% and a specificity of 96.8%. A total score of 36.5 may be the best cut-off value for predicting MHD patients' depression. The scale showed good reliabilities (Cronbach's α value of .759, test-retest reliability of 0.772, and split-half reliability of 0.774). This study found that the LHS-MHD-C is a reliable and valid scale for assessing Chinese MHD patients' helplessness.

Association between malnutrition risk and hemorrhagic transformation in patients with acute ischemic stroke.

Background and aims: Malnutrition is a prevalent problem occurring in different diseases. Hemorrhagic transformation (HT) is a severe complication of acute ischemic stroke (AIS). Few studies have evaluated the association between malnutrition risk and hemorrhagic transformation in patients with acute stroke. We aim to investigate the influence of malnutrition risk on the risk of hemorrhagic transformation in patients with AIS. Methods: A total of 182 consecutive adults with HT and 182 age- and sex-matched patients with stroke were enrolled in this study. The controlling nutritional status (CONUT) score was calculated to evaluate the malnutrition risk. HT was detected by follow-up imaging assessment and was radiologically classified as hemorrhagic infarction type 1 or 2 or parenchymal hematoma type 1 or 2. Logistic regression models were conducted when participants were divided into different malnutrition risk groups according to the objective nutritional score to assess the risk for HT. Results: The prevalence of moderate to severe malnutrition risk in patients with AIS was 12.5%, according to the CONUT score. Univariate analysis showed that the CONUT score is significantly higher in patients with HT than those without HT. After adjusting for potential covariables, the patients with mild risk and moderate to severe malnutrition risk were associated with a higher risk of HT compared to the patients in the normal nutritional status group [odds ratio, 3.180 (95% CI, 1.139-8.874), P = 0.027; odds ratio, 3.960 (95% CI, 1.015-15.453), P = 0.048, respectively]. Conclusion: Malnutrition risk, measured by CONUT score, was significantly associated with an increased risk of hemorrhagic transformation in patients with AIS.

Effects of sugars, fatty acids and amino acids on cytosolic and mitochondrial hydrogen peroxide release from liver cells.

The rates of formation of superoxide and hydrogen peroxide at different electron-donating sites in isolated mitochondria are critically dependent on the substrates that are added, through their effects on the reduction level of each site and the components of the protonmotive force. However, in intact cells the acute effects of added substrates on different sites of cytosolic and mitochondrial hydrogen peroxide production are unclear. Here we tested the effects of substrate addition on cytosolic and mitochondrial hydrogen peroxide release from intact AML12 liver cells. In 30-min starved cells replete with endogenous substrates, addition of glucose, fructose, palmitate, alanine, leucine or glutamine had no effect on the rate or origin of cellular hydrogen peroxide release. However, following 150-min starvation of the cells to deplete endogenous glycogen (and other substrates), cellular hydrogen peroxide production, particularly from NADPH oxidases (NOXs), was decreased, GSH/GSSH ratio increased, and antioxidant gene expression was unchanged. Addition of glucose or glutamine (but not the other substrates) increased hydrogen peroxide release. There were similar relative increases from each of the three major sites of production: mitochondrial sites IQ and IIIQo, and cytosolic NOXs. Glucose supplementation also restored ATP production and mitochondrial NAD reduction level, suggesting that the increased rates of hydrogen peroxide release from the mitochondrial sites were driven by increases in the protonmotive force and the degree of reduction of the electron transport chain. Long-term (24 h) glucose or glutamine deprivation also diminished hydrogen peroxide release rate, ATP production rate and (for glucose deprivation) NAD reduction level. We conclude that the rates of superoxide and hydrogen peroxide production from mitochondrial sites in liver cells are insensitive to extra added substrates when endogenous substrates are not depleted, but these rates are decreased when endogenous substrates are lowered by 150 min of starvation, and can be enhanced by restoring glucose or glutamine supply through improvements in mitochondrial energetic state.