atToc159 is a selective transit peptide receptor for the import of nucleus-encoded chloroplast proteins

The members of the Toc159 family of GTPases act as the primary receptors for the import of nucleus-encoded preproteins into plastids. Toc159, the most abundant member of this family in chloroplasts, is required for chloroplast biogenesis (Bauer, J., K. Chen, A. Hiltbunner, E. Wehrli, M. Eugster, D. Schnell, and F. Kessler. 2000. Nature. 403:203–207) and has been shown to covalently cross-link to bound preproteins at the chloroplast surface (Ma, Y., A. Kouranov, S. LaSala, and D.J. Schnell. 1996. J. Cell Biol. 134:1–13; Perry, S.E., and K. Keegstra. 1994. Plant Cell. 6:93–105). These reports led to the hypothesis that Toc159 functions as a selective import receptor for preproteins that are required for chloroplast development. In this report, we provide evidence that Toc159 is required for the import of several highly expressed photosynthetic preproteins in vivo. Furthermore, we demonstrate that the cytoplasmic and recombinant forms of soluble Toc159 bind directly and selectively to the transit peptides of these representative photosynthetic preproteins, but not representative constitutively expressed plastid preproteins. These data support the function of Toc159 as a selective import receptor for the targeting of a set of preproteins required for chloroplast biogenesis

Effectiveness of Educational Interventions for Health Workers on Antibiotic Prescribing in Outpatient Settings in China: A Systematic Review and Meta-Analysis

Educational interventions are considered an important component of antibiotic stewardship, but their effect has not been systematically evaluated in outpatient settings in China. This research aims to evaluate the effectiveness of educational interventions for health workers on antibiotic prescribing rates in Chinese outpatient settings. Eight databases were searched for relevant randomized clinical trials, non-randomized trials, controlled before-after studies and interrupted time-series studies from January 2001 to July 2021. A total of 16 studies were included in the systematic review and 12 in the meta-analysis. The results showed that educational interventions overall reduced the antibiotic prescription rate significantly (relative risk, RR 0.72, 95% confidence interval, CI 0.61 to 0.84). Subgroup analysis demonstrated that certain features of education interventions had a significant effect on antibiotic prescription rate reduction: (1) combined with compulsory administrative regulations (RR With: 0.65 vs. Without: 0.78); (2) combined with financial incentives (RR With: 0.51 vs. Without: 0.77). Educational interventions can also significantly reduce antibiotic injection rates (RR 0.83, 95% CI 0.74 to 0.94) and the inappropriate use of antibiotics (RR 0.61, 95% CI 0.51 to 0.73). The limited number of high-quality studies limits the validity and reliability of the results. More high-quality educational interventions targeting the reduction of antibiotic prescribing rates are needed

Effects of exercise interventions on negative emotions, cognitive performance and drug craving in methamphetamine addiction

IntroductionMethamphetamine is currently one of the most commonly used addictive substances with strong addiction and a high relapse rate. This systematic review aims to examine the effectiveness of physical activity in improving negative emotions, cognitive impairment, and drug craving in people with methamphetamine use disorder (MUD).MethodsA total of 17 studies out of 133 found from Embase and PubMed were identified, reporting results from 1836 participants from MUD populations. Original research using clearly described physical activity as interventions and reporting quantifiable outcomes of negative mood, cognitive function and drug craving level in people with MUD were eligible for inclusion. We included prospective studies, randomized controlled trials, or intervention studies, focusing on the neurological effects of physical activity on MUD.ResultsTaken together, the available clinical evidence showed that physical activity-based interventions may be effective in managing MUD-related withdrawal symptoms.DiscussionPhysical exercise may improve drug rehabilitation efficiency by improving negative emotions, cognitive behaviors, and drug cravings.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024530359

A NOVEL NON-TOXIC XYLENE SUBSTITUTE (SBO) FOR HISTOLOGY

Xylene has been generally used as a clearing and deparaffinizing agent in histology. Because of the potential toxic and flammable nature of xylene, its substitutes have been introduced into some laboratories. In this study, we introduced a novel, non-toxic xylene substitute (SBO), which was generated through a mixture of 86% of white oil No.2 and 14% of N-heptane. SBO had a high boiling point (188°C) and flash point (144°C) coupled with a scentless and decreased volatility. To compare the effectiveness of SBO and xylene in histology, a wide range of tissue samples from rats and human beings were processed in parallel in SBO and xylene, subjected to various staining procedures. Similar to the xylene-processed paraffin blocks, the SBO-processed counterparts were easy to section without any evidence of cell shrinkage. Assessment of the SBO-treated sections stained with hematoxylin-eosin revealed a good maintenance of cell morphology and structure, and a clear definition of the cytoplasm and the nucleus. Moreover, comparable good results were achieved between the SBO- and xylene-processed tissues in other histochemical and immunohistochemical stainings. Six-month clinical applications at one department of pathology supported the potentials of SBO as a xylene substitute. In conclusion, we suggest that SBO is a safe and efficient substitute of xylene and may probably replace xylene without losing valuable diagnostic information

Prognosis of HIV Patients Receiving Antiretroviral Therapy According to CD4 Counts: A Long-term Follow-up study in Yunnan, China

We aim to evaluate the overall survival and associated risk factors for HIV-infected Chinese patients on antiretroviral therapy (ART). 2517 patients receiving ART between 2006 and 2016 were prospectively enrolled in Yunnan province. Kaplan-Meier analyses and Cox proportional hazard regression analyses were performed. 216/2517 patients died during a median 17.5 (interquartile range [IQR] 6.8-33.2) months of follow-up. 82/216 occurred within 6 months of starting ART. Adjusted hazard ratios were10.69 (95%CI 2.38-48.02, p = 0.002) for old age, 1.94 (95%CI 1.40-2.69, p < 0.0001) for advanced WHO stage, and 0.42 (95%CI 0.27-0.63, p < 0.0001) for heterosexual transmission compared to injecting drug users. Surprisingly, adjusted hazard ratios comparing low CD4 counts group (<50 cells/μl) with high CD4 counts group (≥500 cells/μl) within six months after starting ART was 20.17 (95%CI 4.62-87.95, p < 0.0001) and it declined to 3.57 (95%CI 1.10-11.58, p = 0.034) afterwards. Age, WHO stage, transmission route are significantly independent risk factors for ART treated HIV patients. Importantly, baseline CD4 counts is strongly inversely associated with survival in the first six months; whereas it becomes a weak prognostic factor after six months of starting ART

Negative Elongation Factor Controls Energy Homeostasis in Cardiomyocytes

SummaryNegative elongation factor (NELF) is known to enforce promoter-proximal pausing of RNA polymerase II (Pol II), a pervasive phenomenon observed across multicellular genomes. However, the physiological impact of NELF on tissue homeostasis remains unclear. Here, we show that whole-body conditional deletion of the B subunit of NELF (NELF-B) in adult mice results in cardiomyopathy and impaired response to cardiac stress. Tissue-specific knockout of NELF-B confirms its cell-autonomous function in cardiomyocytes. NELF directly supports transcription of those genes encoding rate-limiting enzymes in fatty acid oxidation (FAO) and the tricarboxylic acid (TCA) cycle. NELF also shares extensively transcriptional target genes with peroxisome proliferator-activated receptor α (PPARα), a master regulator of energy metabolism in the myocardium. Mechanistically, NELF helps stabilize the transcription initiation complex at the metabolism-related genes. Our findings strongly indicate that NELF is part of the PPARα-mediated transcription regulatory network that maintains metabolic homeostasis in cardiomyocytes

A correlation analysis of HHV infection and its predictive factors in an HIV-seropositive population in Yunnan, China

Human herpesviruses (HHVs) have a particularly high prevalence in certain high-risk populations and cause increased morbidity and mortality in patients with acquired immunodeficiency syndrome (AIDS). Screening and treating subclinical HHV infections reduce human immunodeficiency virus (HIV) infection incidence, disease progression, and transmission. However, there are few studies on HHVs, HIV coinfection rates, and their related risk factors. We aimed to clarify the prevalence of all eight HHVs in peripheral blood samples collected from HIV-positive patients, and explore the association of HHV infection in HIV-positive patients in an HIV-seropositive population in Yunnan. We recruited 121 HIV-positive patients with highly active antiretroviral therapy (HAART) and 45 healthy individuals. All the eight HHVs were detected using polymerase chain reaction and their epidemiological information and clinical data were collected and statistically analyzed. A high prevalence of HHVs (89.3%) was observed in individuals with HIV infections and with herpes simplex virus (HSV)-2 (65.3%), and HSV-1 (59.5%) being the most common. Coinfection with more than two different HHVs was more common in patients with HIV infections receiving HAART (72.7%) than in healthy controls. Older age, being married, higher HIV-1 plasma viral loads, and use of antiviral protease inhibitors were independently correlated with an increased frequency of HHVs, but we found no association with CD4 count, WHO HIV clinical stage, and HIV infection duration. Our findings are of great significance for the prevention of HHV opportunistic infection in patients with AIDS and their clinical treatment

A study on the treatment effects of Crataegus pinnatifida polysaccharide on non-alcoholic fatty liver in mice by modulating gut microbiota

The objective of this study was to investigate the protective effect of Crataegus pinnatifida polysaccharide (CPP) on non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD) in mice. The findings demonstrated that CPP improved free fatty acid (FFA)-induced lipid accumulation in HepG2 cells and effectively reduced liver steatosis and epididymal fat weight in NAFLD mice, as well as decreased serum levels of TG, TC, AST, ALT, and LDL-C. Furthermore, CPP exhibited inhibitory effects on the expression of fatty acid synthesis genes FASN and ACC while activating the expression of fatty acid oxidation genes CPT1A and PPARα. Additionally, CPP reversed disturbances in intestinal microbiota composition caused by HFD consumption. CPP decreased the firmicutes/Bacteroidetes ratio, increased Akkermansia abundance, and elevated levels of total short-chain fatty acid (SCFA) content specifically butyric acid and acetic acid. Our results concluded that CPP may intervene in the development of NAFLD by regulating of intes-tinal microbiota imbalance and SCFAs production. Our study highlights that CPP has a potential to modulate lipid-related pathways via alterations to gut microbiome composition thereby ex-erting inhibitory effects on obesity and NAFLD development

Increased Functional Connectivity Between Medulla and Inferior Parietal Cortex in Medication-Free Major Depressive Disorder

Emerging evidence has documented the abnormalities of primary brain functions in major depressive disorder (MDD). The brainstem has shown to play an important role in regulating basic functions of the human brain, but little is known about its role in MDD, especially the roles of its subregions. To uncover this, the present study adopted resting-state functional magnetic resonance imaging with fine-grained brainstem atlas in 23 medication-free MDD patients and 34 matched healthy controls (HC). The analysis revealed significantly increased functional connectivity of the medulla, one of the brainstem subregions, with the inferior parietal cortex (IPC) in MDD patients. A positive correlation was further identified between the increased medulla-IPC functional connectivity and Hamilton anxiety scores. Functional characterization of the medulla and IPC using a meta-analysis revealed that both regions primarily participated in action execution and inhibition. Our findings suggest that increased medulla-IPC functional connectivity may be related to over-activity or abnormal control of negative emotions in MDD, which provides a new insight for the neurobiology of MDD

Modeling Rett Syndrome Using TALEN-Edited MECP2 Mutant Cynomolgus Monkeys

Gene-editing technologies have made it feasible to create nonhuman primate models for human genetic disorders. Here, we report detailed genotypes and phenotypes of TALEN-edited MECP2 mutant cynomolgus monkeys serving as a model for a neurodevelopmental disorder, Rett syndrome (RTT), which is caused by loss-of-function mutations in the human MECP2 gene. Male mutant monkeys were embryonic lethal, reiterating that RTT is a disease of females. Through a battery of behavioral analyses, including primate-unique eye-tracking tests, in combination with brain imaging via MRI, we found a series of physiological, behavioral, and structural abnormalities resembling clinical manifestations of RTT. Moreover, blood transcriptome profiling revealed that mutant monkeys resembled RTT patients in immune gene dysregulation. Taken together, the stark similarity in phenotype and/or endophenotype between monkeys and patients suggested that gene-edited RTT founder monkeys would be of value for disease mechanistic studies as well as development of potential therapeutic interventions for RTT