The RING-finger ubiquitin E3 ligase TaPIR1 targets TaHRP1 for degradation to suppress chloroplast function.

Chloroplasts are key players in photosynthesis and immunity against microbial pathogens. However, the precise and timely regulatory mechanisms governing the control of photosynthesis-associated nuclear genes (PhANGs) expression in plant immunity remain largely unknown. Here we report that TaPIR1, a Pst-induced RING-finger E3 ubiquitin ligase, negatively regulates Pst resistance by specifically interacting with TaHRP1, an atypical transcription factor histidine-rich protein. TaPIR1 ubiquitinates the lysine residues K131 and K136 in TaHRP1 to regulate its stability. TaHRP1 directly binds to the TaHRP1-binding site elements within the PhANGs promoter to activate their transcription via the histidine-rich domain of TaHRP1. PhANGs expression induces the production of chloroplast-derived ROS. Although knocking out TaHRP1 reduces Pst resistance, TaHRP1 overexpression contributes to photosynthesis, and chloroplast-derived ROS production, and improves disease resistance. TaPIR1 expression inhibits the downstream activation of TaHRP1 and TaHRP1-induced ROS accumulation in chloroplasts. Overall, we show that the TaPIR1-mediated ubiquitination and degradation of TaHRP1 alters PhANGs expression to disrupt chloroplast function, thereby increasing plant susceptibility to Pst.

Case report: ATM A1159T mutation in malignant peritoneal mesothelioma may be associated with tumor recurrence.

Malignant peritoneal mesothelioma is an exceedingly rare malignant tumor. Herein, we present a case of malignant peritoneal mesothelioma in a 59-year-old Chinese female patient who was stable after treatment for multiple relapses. Imaging revealed massive ascites and an irregular thickening of the peritoneal mesangium. Laparoscopic biopsy revealed heterogeneous cell nests in the parietal peritoneal fibrous tissue, which were confirmed by immunohistochemical staining for Calretinin, WT-1, and D2-40. In terms of genetic screening, BAP1, CSF1R, and other key driver gene variants closely related to malignant peritoneal mesothelioma have been explored in tumor tissues. Notably, CARD11 driver mutation was first found in all malignant peritoneal mesothelioma patients, and ATM A1159T gene mutation found in recurrent focal tissue may be associated with recurrent tumor recurrence.

Vitamin D/vitamin D receptor protects intestinal barrier against colitis by positively regulating Notch pathway.

Objective: Vitamin D/Vitamin D receptor (VD/VDR) signaling and the Notch pathway are involved in intestinal barrier restoration in colitis; however, their relationship and underlying mechanism are largely unknown. Therefore, this study aimed to investigate the role and mechanism of VD/VDR and the Notch pathways in intestinal barrier protection. Methods: Genetic Vdr knockout (VDR KO) and VD deficient (VDd) mice were established, and colitis was induced by feeding 2.5% dextran sodium sulfate (DSS) water. Mechanistic studies, including real-time PCR, immunofluorescence, Western blotting and dual-luciferase reporter assays, were performed on cultured Caco-2 cells and intestinal organoids. Results: VD deficiency and VDR genetical KO increased the severity of DSS-induced colitis in mice, which presented a higher disease activity index score, increased intestinal permeability, and more severe intestinal histological damage than controls, accompanied by decreased and disrupted claudin-1 and claudin-3. Moreover, inhibition of Notch pathway by LY411,575 aggravated the severity of DSS-induced colitis and intestinal injury. In Caco-2 cells and intestinal organoids, the expression of Notch-1, N1ICD and Hes1 decreased upon downregulation or KO of VDR but increased upon paricalcitol (PAR, a VDR agonist) treatment. Meanwhile, PAR rescued claudin-1 and claudin-3 impairments that resulted from TNF-α exposure but failed to restore claudin-3 upon Notch inhibition. The dual-luciferase reporter assay further suggested that VD/VDR positively regulated the Notch signaling pathway by modulating Notch-1 transcription. Conclusion: VD/VDR positively modulates Notch activation by promoting Notch-1 transcription to maintain intestinal tight junction integrity and barrier function. This highlights the VD/VDR-Notch pathway as a potential new therapeutic target for protecting the intestinal barrier against ulcerative colitis.

Metabolomics and transcriptomics combined with physiology reveal key metabolic pathway responses in tobacco roots exposed to NaHS.

Hydrogen sulfide (H2S) has emerged as a novel endogenous gas signaling molecule, joining the ranks of nitric oxide (NO) and carbon monoxide (CO). Recent research has highlighted its involvement in various physiological processes, such as promoting root organogenesis, regulating stomatal movement and photosynthesis, and enhancing plant growth, development, and stress resistance. Tobacco, a significant cash crop crucial for farmers' economic income, relies heavily on root development to affect leaf growth, disease resistance, chemical composition, and yield. Despite its importance, there remains a scarcity of studies investigating the role of H2S in promoting tobacco growth. This study exposed tobacco seedlings to different concentrations of NaHS (an exogenous H2S donor) - 0, 200, 400, 600, and 800 mg/L. Results indicated a positive correlation between NaHS concentration and root length, wet weight, root activity, and antioxidant enzymatic activities (CAT, SOD, and POD) in tobacco roots. Transcriptomic and metabolomic analyses revealed that treatment with 600 mg/L NaHS significantly effected 162 key genes, 44 key enzymes, and two metabolic pathways (brassinosteroid synthesis and aspartate biosynthesis) in tobacco seedlings. The addition of exogenous NaHS not only promoted tobacco root development but also potentially reduced pesticide usage, contributing to a more sustainable ecological environment. Overall, this study sheds light on the primary metabolic pathways involved in tobacco root response to NaHS, offering new genetic insights for future investigations into plant root development.

Atmospheric H2O2 during haze episodes in a Chinese megacity: Concentration, source, and implication on sulfate production.

Atmospheric hydrogen peroxide (H2O2), as an important oxidant, plays a key role in atmospheric chemistry. To reveal its characteristics in polluted areas, comprehensive observations were conducted in Zhengzhou, China from February 22 to March 4, 2019, including heavy pollution days (HP) and light pollution days (LP). High NO concentrations (18 ± 26 ppbv) were recorded in HP, preventing the recombination reaction of two HO2• radicals. Surprisingly, higher concentrations of H2O2 were observed in HP (1.5 ± 0.6 ppbv) than those in LP (1.2 ± 0.6 ppbv). In addition to low wind speed and relative humidity, the elevated H2O2 in HP could be mainly attributed to intensified particle-phase photoreactions and biomass burning. In terms of sulfate formation, transition-metal ions (TMI)-catalyzed oxidation emerged as the predominant oxidant pathway in both HP and LP. Note that the average H2O2 oxidation rate increased from 3.6 × 10-2 in LP to 1.1 × 10-1 µg m-3 h-1 in HP. Moreover, the oxidation by H2O2 might exceed that of TMI catalysis under specific conditions, emerging as the primary driver of sulfate formation.

Rash caused by lurasidone in old chinese patient with bipolar disorder: case-based review.

BACKGROUND: Rash is one of common adverse drug reaction and which have been reported in typical and atypical antipsychotics. Reports of lurasidone induced skin reactions are sparse. In this study, we report a case of rash caused by lurasidone. CASE PRESENTATION: A 63-year-old man with bipolar disorder (BD) who is treated by lurasidone. However, the patient presents a rash all over after lurasidone dose increasing from 40 mg/day to 60 mg/day. With the diagnosis of drug induced rash, lurasidone was discontinued, and the rash complete disappears within 2 weeks. In addition, all case reports about antipsychotics associated rash were reviewed by searching English and Chinese database including Pubmed, Embase, Cochrane Library, CNKI and Wanfang database. A total of 139 articles contained 172 patients were included in our study. The literature review and our case suggest that the cutaneous adverse events caused by antipsychotic drugs should not be ignored, particularly for the patient who was first use or at dose increasing of antipsychotic. CONCLUSIONS: In conclusion, we report a case of lurasidone related rash and review rash caused by antipsychotics. Psychiatrists should be alert to the possibility of the rash caused by antipsychotics, especially the patient was first use of antipsychotics or the antipsychotic dose was increasing.

Poly(3,4-dihydroxyphenylalanine)-modified cellulose paper for the extraction of deoxyribonucleic acid by a laboratory-built automated extraction device.

The success of polymerase chain reaction (PCR) depends on the quality of deoxyribonucleic acid (DNA) templates. This study developed a cost-effective and eco-friendly DNA extraction system utilizing poly(3,4-dihydroxyphenylalanine)-modified cellulose paper (polyDOPA@paper). PolyDOPA@paper was prepared by oxidatively self-polymerizing DOPA under weak alkaline conditions and utilizing the adhesive property of polyDOPA on different materials. Compared to the uncoated cellulose paper, polyDOPA coating significantly enhances DNA adsorption owing to its abundant amino, carboxyl, and hydroxyl moieties. The DNA extraction mechanism using polyDOPA@paper was discussed. The maximum adsorption capacity of polyDOPA@paper for DNA was 20.7 µg cm-2. Moreover, an automated extraction system was designed and fabricated using 3D printing technology. The device simplifies the operation and ensures the reproducibility and consistency of the results. More importantly, it eliminates the need for specialized training of operators. The feasibility of the polyDOPA@paper-based automated extraction system was evaluated by quantitatively detecting Escherichia coli in spiked milk samples via a real-time PCR. The detection limit was 102 cfu mL-1. The results suggest that the system would have significant potential in detecting pathogens.

Associations of body mass index, waist circumference and the weight-adjusted waist index with daily living ability impairment in older Chinese people: A cross-sectional study of the Chinese Longitudinal Healthy Longevity Survey.

AIM: To investigate the associations of body mass index (BMI), waist circumference (WC) and the weight-adjusted waist index (WWI) with the impairment of activities of daily living (ADL) in older Chinese people. METHODS: A total of 13 260 participants aged 65 years and older from the 2018 Chinese Longitudinal Healthy Longevity Survey were included in this cross-sectional study. BMI, WC and the WWI were calculated from measurements of height, weight and WC. Binary logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Non-linear correlations were investigated using restricted cubic spline curves. RESULTS: In multivariate logistic regression fully adjusted for confounding variables, our analyses revealed significant associations between WC and WWI and ADL impairment, with adjusted ORs (95% CI) of 1.01 (1.00, 1.01) and 1.08 (1.03, 1.12), respectively. Meanwhile, participants with a high WWI had a higher risk of ADL impairment compared with those with a low WWI, with an adjusted OR (95% CI) of 1.12 (1.02, 1.23). Subgroup analyses showed that only the association between WWI and ADL impairment did not differ in any of the different populations. In addition, we found that BMI, WC and WWI were non-linearly associated with ADL impairment. CONCLUSIONS: There are significant associations between WC and WWI and ADL impairment in older Chinese people. The findings show the ability of the WWI to serve as a comprehensive and effective indicator of obesity in older Chinese people and emphasize the importance of assessing WWI in screening and preventing ADL impairment in older people.

Highly sensitive detection of Salmonella typhimurium via gold and magnetic nanoparticle-mediated sandwich hybridization coupled with ICP-MS.

Foodborne pathogens including Salmonella typhimurium (S. typhimurium) are responsible for over 600 million global incidences of illness annually, posing a significant threat to public health. Inductively coupled plasma mass spectrometry (ICP-MS), coupled with element labeling strategies, has emerged as a promising platform for multivariate and accurate pathogen detection. However, achieving high specificity and sensitivity remains a critical challenge. Herein, we synthesize clustered magnetic nanoparticles (MNPs) and popcorn-shaped gold nanoparticles (AuNPs) to conjugate capture and report DNA probes for S. typhimurium, respectively. These engineered nanoparticles facilitate the identification of S. typhimurium DNA through a sandwich hybridization technique. ICP-MS quantification of Au within the sandwich-structure complexes allows for precise S. typhimurium detection. The unique morphology of the AuNPs and MNPs increases the available sites for probe attachment, enhancing the efficiency of S. typhimurium DNA capture, broadening the detection range to 101-1010 copies mL-1, and achieving a low detection limit of 1 copy mL-1, and the overall assay time is 70 min. The high specificity of this method is verified by anti-interference assays against ten other pathogens. The recovery was 96.8-102.8% for detecting S. typhimurium DNA in biological samples. As these specially designed nanoparticles may facilitate the attachment of various proteins and nucleic acid probes, they may become an effective platform for detecting multiple pathogens.

Cost-Effectiveness Analysis of 6 Tyrosine Kinase Inhibitors as First-Line Treatment for ALK-Positive NSCLC in China.

Background: Lung cancer ranks first in both cancer incidence and mortality in China. The emergence of novel treatments for ALK-positive NSCLC led to an improvement in survival and quality of life for patients with advanced ALK mutation-positive non-small cell lung cancer (NSCLC). This study sought to assess the cost-effectiveness of 6 tyrosine kinase inhibitors (TKIs)-crizotinib, alectinib, ceritinib, brigatinib, ensartinib, and lorlatinib-as first-line treatments for ALK-positive NSCLC from the perspective of the Chinese health care system. Methods: A Markov model was developed to estimate the cost-effectiveness of these 6 TKIs. In this model, ALK-positive NSCLC patients were initially simulated to receive 1 of the 6 TKIs as first-line therapy, followed by different TKIs as subsequent treatment and salvage chemotherapy as last-line treatment. Survival data were sourced from the latest published clinical trials. Costs were derived from recent national health insurance negotiations and hospital information systems of selected health care facilities. Utilities for healthy states and adverse events were obtained from the literature. One-way and probabilistic sensitivity analysis as well as scenario analysis was conducted to assess the robustness of the results. Results: Compared to ensartinib, crizotinib, alectinib, ceritinib, brigatinib, and lorlatinib demonstrated incremental quality-adjusted life years (QALYs) of -1.13, 0.39, -0.58, -0.09, and 0.35, respectively. The corresponding incremental costs were $10 677, $33 501, -$6426, $2672, and $24 358. This resulted in ICERs of -$9449/QALY, $85 900/QALY, $11 079/QALY, $29 689/QALY and $69 594/QALY, respectively. Conclusion: Crizotinib was considered to be absolutely dominated by ensartinib. Under a willingness-to-pay threshold of $38 223/QALY, ceritinib and brigatinib were cost-effective compared with ensartinib, while lorlatinib and alectinib were not cost-effective when compared with ensartinib. Overall, brigatinib emerged as the most cost-effective treatment among all the options considered.

Latest insights into the epidemiology, characteristics, and therapeutic strategies of chronic hepatitis B patients in indeterminate phase.

As a hepatotropic virus, hepatitis B virus (HBV) can establish a persistent chronic infection in the liver, termed, chronic hepatitis B (CHB), which causes a series of liver-related complications, including fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). HCC with HBV infection has a significantly increased morbidity and mortality, whereas it could be preventable. The current goal of antiviral therapy for HBV infection is to decrease CHB-related morbidity and mortality, and achieve sustained suppression of virus replication, which is known as a functional or immunological cure. The natural history of chronic HBV infection includes four immune phases: the immune-tolerant phase, immune-active phase, inactive phase, and reactivation phase. However, many CHB patients do not fit into any of these defined phases and are regarded as indeterminate. A large proportion of indeterminate patients are only treated with dynamic monitoring rather than recommended antiviral therapy, mainly due to the lack of definite guidelines. However, many of these patients may gradually have significant liver histopathological changes during disease progression. Recent studies have focused on the prevalence, progression, and carcinogenicity of indeterminate CHB, and more attention has been given to the prevention, detection, and treatment for these patients. Herein, we discuss the latest understanding of the epidemiology, clinical characteristics, and therapeutic strategies of indeterminate CHB, to provide avenues for the management of these patients.

Pathogen detection via inductively coupled plasma mass spectrometry analysis with nanoparticles.

Infections caused by viruses and bacteria pose a significant threat to global public health, emphasizing the critical importance of timely and precise detection methods. Inductively coupled plasma mass spectrometry (ICP-MS), a contemporary approach for pathogen detection, offers distinct advantages such as high sensitivity, a wide linear range, and multi-index capabilities. This review elucidates the underexplored application of ICP-MS in conjunction with functional nanoparticles (NPs) for the identification of viruses and bacteria. The review commences with an elucidation of the underlying principles, procedures, target pathogens, and NP requirements for this innovative approach. Subsequently, a thorough analysis of the advantages and limitations associated with these techniques is provided. Furthermore, the review delves into a comprehensive examination of the challenges encountered when utilizing NPs and ICP-MS for pathogen detection, culminating in a forward-looking assessment of the potential pathways for advancement in this domain. Thus, this review contributes novel perspectives to the field of pathogen detection in biomedicine by showcasing the promising synergy of ICP-MS and NPs.

Metabolomic analysis of the Puerarin hypoglycemic activity via AMPK-mTOR and PPARγ-NF-κB signaling pathways.

BACKGROUND: Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycemia, and its increasing prevalence is a global concern. Early diagnostic markers and therapeutic targets are essential for DM prevention and treatment. Pueraria, derived from kudzu root, is used clinically for various symptoms, and its active compound, Puerarin, shows promise in improving insulin resistance and reducing inflammation. PURPOSE: This study aims to evaluate the protective effects of metformin and Puerarin at different doses in an STZ-induced DM mouse model. The intricate metabolites within the serum of STZ-induced diabetic mice were subjected to thorough investigation, thus elucidating the intricate mechanism through which Puerarin demonstrates notable efficacy in the treatment of diabetes. METHODS: An STZ-induced DM mouse model is established. Mice are treated with metformin and puerarin at varying doses. Physiological, biochemical, and histomorphological assessments are performed. Metabolomics analysis is carried out on serum samples from control, DM, metformin, and medium-dose Puerarin groups. Western blot and qRT-PCR technologies are used to validate the mechanisms. RESULTS: The DM mouse model replicates abnormal blood glucose, insulin levels, physiological, biochemical irregularities, as well as liver and pancreas damage. Treatment with metformin and Puerarin restores these abnormalities, reduces organ injury, and modulates AMPK, PPARγ, mTOR, and NF-κB protein and mRNA expression. Puerarin activates the AMPK-mTOR and PPARγ-NF-κB signaling pathways, regulating insulin signaling, glucolipid metabolism, and mitigating inflammatory damage. CONCLUSION: This study demonstrates that Puerarin has the potential to treat diabetes by modulating key signaling pathways. The focus was on the finding that Puerarin has been shown to improve insulin signaling, glucolipid metabolism and attenuate inflammatory damage through the modulation of the AMPK-mTOR and PPARγ-NF-κB pathways. The discovery of Puerarin's favorable protective effect and extremely complex mechanism highlights its prospect in the treatment of diabetes and provides theoretical support for its comprehensive development and utilization.

Temperature measurement accuracy of peripheral thermometer in the pediatric emergency department: A meta-analysis and systematic review.

BACKGROUND: It is necessary to evaluate the accuracy of peripheral thermometer in outpatient and emergency temperature measurement of children by diagnostic meta-analysis, to provide evidence for clinical temperature measurement and nursing care of children. METHODS: Two authors searched PubMed, Web of science, CINAHL, EBSCO, OVID, Embase, CNKI, Wanfang and Weipu databases for studies on the temperature measurement accuracy of peripheral thermometer in children in outpatient and emergency department until November 20, 2023. RESULTS: 10 studies involving 3448 children were included. The combined sensitivity was 82 % (95 % CI: 81 % ∼ 84 %), the combined specificity was 88 % (95 % CI: 87 % ∼ 89 %), the combined positive likelihood ratio was 11. 35 (95 % CI: 6. 07 âˆ¼ 21). 20), the combined negative likelihood ratio was 0.20 (95 % CI: 0.14 âˆ¼ 0.29). The odds ratio of combined diagnosis was 58.02 (95 % CI: 30.66 âˆ¼ 109.76), and the area under ROC curve (AUC) was 0.95. CONCLUSIONS: The peripheral temperature measurement can reflect a certain core temperature, among which the infrared tympanic membrane thermometer has the highest sensitivity, which is worthy of clinical application.

Advancements in Ultrasound Techniques for Evaluating Intracranial Pressure Through Optic Nerve Sheath Diameter Measurement.

Elevated intracranial pressure (ICP) in patients with cerebral lesions has garnered considerable attention in research. It often manifests as a common symptom in conditions such as intracranial tumors, intracerebral hemorrhage, and cerebral edema. This paper provides an overview of ICP concepts, discusses the advantages and disadvantages of traditional monitoring methods, explores the physiological and anatomical aspects of the optic nerve sheath, examines the utility of ultrasound measurement of optic nerve sheath diameter (ONSD) in both nervous system and nonnervous system disorders, and outlines the cutoff values and normal ranges for assessing elevated ICP using ultrasound measurement of ONSD. The review underscores ultrasound measurement of ONSD as a promising noninvasive, safe, straightforward, and repeatable examination technique for various diseases. Nevertheless, the lack of standardized cutoff values for elevated ICP remains a challenge. Summarizing studies on optic nerve sheaths is crucial for enhancing the efficacy of ultrasound measurement of ONSD in assessing ICP.

Professional characteristics, numbers, distribution and training of China's mental health workforce from 2000 to 2020: a scoping review.

Over the last 20 years, the numbers, types, distribution, and qualifications of mental health professionals in China have changed dramatically. However, there has been no systematic attempt to collect information about this transformation in the human resources available to provide mental health services-information that needs to be regularly updated to improve the country's coordination of these services. This scoping review compiles current details about China's mental health workforce and identifies critical gaps in available research and reporting. We reviewed all relevant studies and reports published between 1 January 2000 and 30 June 2021 in two English-language and four Chinese-language databases, the website of China's National Health Commission, and national and provincial health services yearbooks. In addition to summarising data from government yearbooks, we integrated relevant results from 82 peer-reviewed publications and two government reports. From 2000 to 2020, the number of psychiatrists in the country increased by 139%, and the number of psychiatric nurses increased by 340%. However, the much higher ratio of mental health professionals per 100,000 population and the better quality of training of mental health professionals in urban, eastern provinces compared to rural, western provinces has not changed. Progress has been made in standardising the training of psychiatrists, but there are no standardised training programs for psychiatric nurses, clinical psychologists, or psychiatric social workers. Future research needs to address several issues that limit the effectiveness of policies aimed at increasing the size, quality and equitable distribution of China's mental health workforce: 1) limited data available about the numbers and characteristics of professionals who provide mental health services, 2) absence of nationally standardised training programs for non-psychiatric medical professionals and non-medical personnel who provide essential monitoring and supportive care to persons with mental illnesses, and 3) failure to scientifically assess the outcomes of currently available training programs.

High-Branched Natural Polysaccharide Flaxseed Gum Binder for Silicon-Based Lithium-Ion Batteries with High Capacity.

Silicon-based anodes heavily depend on the binder to preserve the unbroken electrode structure. In the present work, natural flaxseed gum (FG) is used as a binder of silicon nanoparticles (SiNPs) anode for the first time. Owing to a large number of polar groups and a rich branched structure, this material not only anchors tightly to the surface of SiNPs through bonding interactions but also formed a hydrogen bonding network structure among molecules. As a result, the FG binder can endow the silicon electrode with stable interfacial adhesion and outstanding mechanical properties. In addition, FG with a high viscosity facilitates the homogeneous dispersion of the electrode components. When FG is used as a binder, the cycling performance of the Si anode is greatly improved. After one hundred cycles at an applied current density of 1 A g-1, the electrode continues to display remarkable electrochemical properties with a significant cyclic capacity (2213 mA h g-1) and initial Coulombic efficiency (ICE) of 89.7%.