NSUN5/TET2-directed chromatin-associated RNA modification of 5-methylcytosine to 5-hydroxymethylcytosine governs glioma immune evasion.

Malignant glioma exhibits immune evasion characterized by highly expressing the immune checkpoint CD47. RNA 5-methylcytosine(m5C) modification plays a pivotal role in tumor pathogenesis. However, the mechanism underlying m5C-modified RNA metabolism remains unclear, as does the contribution of m5C-modified RNA to the glioma immune microenvironment. In this study, we demonstrate that the canonical 28SrRNA methyltransferase NSUN5 down-regulates ß-catenin by promoting the degradation of its mRNA, leading to enhanced phagocytosis of tumor-associated macrophages (TAMs). Specifically, the NSUN5-induced suppression of ß-catenin relies on its methyltransferase activity mediated by cysteine 359 (C359) and is not influenced by its localization in the nucleolus. Intriguingly, NSUN5 directly interacts with and deposits m5C on CTNNB1 caRNA (chromatin-associated RNA). NSUN5-induced recruitment of TET2 to chromatin is independent of its methyltransferase activity. The m5C modification on caRNA is subsequently oxidized into 5-hydroxymethylcytosine (5hmC) by TET2, which is dependent on its binding affinity for Fe2+ and α-KG. Furthermore, NSUN5 enhances the chromatin recruitment of RBFOX2 which acts as a 5hmC-specific reader to recognize and facilitate the degradation of 5hmC caRNA. Notably, hmeRIP-seq analysis reveals numerous mRNA substrates of NSUN5 that potentially undergo this mode of metabolism. In addition, NSUN5 is epigenetically suppressed by DNA methylation and is negatively correlated with IDH1-R132H mutation in glioma patients. Importantly, pharmacological blockage of DNA methylation or IDH1-R132H mutant and CD47/SIRPα signaling synergistically enhances TAM-based phagocytosis and glioma elimination in vivo. Our findings unveil a general mechanism by which NSUN5/TET2/RBFOX2 signaling regulates RNA metabolism and highlight NSUN5 targeting as a potential strategy for glioma immune therapy.

Complex decay dynamics of HIV virions, intact and defective proviruses, and 2LTR circles following initiation of antiretroviral therapy.

In persons living with HIV-1 (PLWH) who start antiretroviral therapy (ART), plasma virus decays in a biphasic fashion to below the detection limit. The first phase reflects the short half-life (<1 d) of cells that produce most of the plasma virus. The second phase represents the slower turnover (t1/2 = 14 d) of another infected cell population, whose identity is unclear. Using the intact proviral DNA assay (IPDA) to distinguish intact and defective proviruses, we analyzed viral decay in 17 PLWH initiating ART. Circulating CD4+ T cells with intact proviruses include few of the rapidly decaying first-phase cells. Instead, this population initially decays more slowly (t1/2 = 12.9 d) in a process that largely represents death or exit from the circulation rather than transition to latency. This more protracted decay potentially allows for immune selection. After ∼3 mo, the decay slope changes, and CD4+ T cells with intact proviruses decay with a half-life of 19 mo, which is still shorter than that of the latently infected cells that persist on long-term ART. Two-long-terminal repeat (2LTR) circles decay with fast and slow phases paralleling intact proviruses, a finding that precludes their use as a simple marker of ongoing viral replication. Proviruses with defects at the 5' or 3' end of the genome show equivalent monophasic decay at rates that vary among individuals. Understanding these complex early decay processes is important for correct use of reservoir assays and may provide insights into properties of surviving cells that can constitute the stable latent reservoir.

Measuring the latent reservoir for HIV-1: Quantification bias in near full-length genome sequencing methods.

Antiretroviral therapy (ART) effectively inhibits HIV-1 replication but is not curative due to the persistence of a latent viral reservoir in resting CD4+ T cells. This reservoir is a major barrier to cure. Sequencing studies have revealed that the population of proviruses persisting in ART-treated individuals is dominated by defective proviruses that cannot give rise to viral rebound due to fatal defects including large deletions and APOBEC3-mediated hypermutation. Near full genome sequencing (nFGS) of individual proviruses is used in reservoir assays to provide an estimate of the fraction of proviruses that are intact. nFGS methods rely on a long-distance outer PCR capturing most (~9 kb) of the genome, followed by nested inner PCRs. The outer PCR is carried out at limit dilution, and interpretation of the results is based on the assumption that all proviruses are quantitatively captured. Here, we evaluate nFGS methods using the intact proviral DNA assay (IPDA), a multiplex digital droplet PCR assay that quantitates intact and defective proviruses with single molecule sensitivity using only short, highly efficient amplicons. We analyzed proviral templates of known sequence to avoid the additional complication of sequence polymorphism. With the IPDA, we quantitated molecular yields at each step of nFGS methods. We demonstrate that nFGS methods are inefficient and miss ~70% of full-length proviruses due to amplification failure at the initial outer PCR step. In contrast, proviruses with large internal deletions encompassing 70% of the genome can be quantitatively amplified under the same conditions. Accurate measurement of the latent reservoir of HIV-1 is essential for evaluating the efficacy of cure strategies, and the bias against full length proviruses in nFGS methods must be considered.

Low phosphorus increases hepatic lipid deposition, oxidative stress and inflammatory response via Acetyl-CoA carboxylase-dependent manner in zebrafish liver cells.

Acetyl-CoA carboxylase (ACC) plays a regulatory role in both fatty acid synthesis and oxidation, controlling the process of lipid deposition in the liver. Given that existing studies have shown a close relationship between low phosphorus (P) and hepatic lipid deposition, this study was conducted to investigate whether ACC plays a crucial role in this relationship. Zebrafish liver cell line (ZFL) was incubated under low P medium (LP, P concentration: 0.77 mg/L) or adequate P medium (AP, P concentration: 35 mg/L) for 240 h. The results showed that, compared with AP-treated cells, LP-treated cells displayed elevated lipid accumulation, and reduced fatty acid ß-oxidation, ATP content, and mitochondrial mass. Furthermore, transcriptomics analysis revealed that LP-treated cells significantly increased lipid synthesis (Acetyl-CoA carboxylases (acc), Stearyl coenzyme A dehydrogenase (scd)) but decreased fatty acid ß-oxidation (Carnitine palmitoyltransferase I (cptI)) and (AMP-activated protein kinase (ampk)) mRNA levels compared to AP-treated cells. The phosphorylation of AMPK and ACC, and the protein expression of CPTI were significantly decreased in LP-treated cells compared with those in AP-treated cells. After 240 h of LP treatment, PF-05175157 (an ACC inhibitor) was supplemented in the LP treatment for an additional 12 h. PF-05175157-treated cells showed higher phosphorylation of ACC, higher protein expression of CPTI, and lower protein expression of FASN, lower TG content, enhanced fatty acid ß-oxidation, increased ATP content, and mitochondrial mass compared with LP-treated cells. PF-05175157 also relieved the LP-induced oxidative stress and inflammatory response. Overall, these findings suggest that ACC is a promising target for treating LP-induced elevation of lipid deposition in ZFL, and can alleviate oxidative stress and inflammatory response.

Omeprazole taken once every other day can effectively prevent aspirin-induced gastrointestinal mucosal damage in rats.

BACKGROUND: Proton-pump inhibitors (PPIs) prevent aspirin-associated gastric and duodenal mucosal damage. However, long-term use of PPIs can lead to various adverse reactions, such as gastric polyps and enterochromaffin-like cell hyperplasia. Current research indicates that the abovementioned adverse reactions are mainly related to hypergastrinemia. We investigated whether low-frequency administration of omeprazole could effectively repair aspirin-induced mucosal damage and reduce the increase in gastrin levels associated with long-term use of PPIs. METHODS: Sprague‒Dawley rats were divided into four treatment groups: daily aspirin, daily aspirin and omeprazole once every day (qd), daily aspirin and omeprazole once every other day (qod), and daily aspirin and omeprazole once every three days (1/d3). After 15 days of feeding, blood samples were collected, and the stomachs of sacrificed rats were subjected to macroscopic, histological, and immunohistochemical studies. Moreover, in clinical practice, patients with peptic ulcers caused by aspirin took a standard dose of omeprazole (20 mg) every other day. Two months later, gastroscopy was performed to examine the healing of the ulcers. RESULTS: Both the omeprazole qd and omeprazole qod administrations effectively prevented aspirin-induced gastric peptic ulcers, with no significant difference between the two groups in the inhibition of parietal cell secretion of gastric acid and cell apoptosis. However, omeprazole 1/d3 failed to completely prevent aspirin-induced gastric mucosal injury. Notably, the gastrin levels, cell proliferation ability and cholecystokinin B receptor expression of the omeprazole qd group were significantly higher than those of the omeprazole qod group. In clinical work, patients with peptic ulcers caused by aspirin were given a standard dose of omeprazole every other day, and their ulcers healed after 2 months, as observed by gastroscopy. CONCLUSIONS: Omeprazole administration once every other day can effectively prevent aspirin-induced peptic ulcers and reduce hypergastrinemia, which may reduce the long-term adverse effects of PPI treatment.

Alisol A inhibits the circ_0001831/miR-346/LIN28B pathway to ameliorate high glucose-induced injury of human renal mesangial cells.

BACKGROUND: Alisol A can ameliorate glucose metabolism disorders, however, there is no data regarding its role in diabetic nephropathy (DN). The present work evaluates the role of Alisol A in DN and the underlying mechanism. METHODS: RNA expression of circ_0001831, miR-346, and lin-28 homolog B (LIN28B) was detected by qRT-PCR. Cell viability and proliferation were investigated by MTT assay and EdU assay, respectively. The inflammatory cytokines were examined by ELISAs. Oxidative stress was evaluated by the commercial kits. Protein expression was detected by western blotting. The interactions among circ_0001831, miR-346, and LIN28B were identified by dual-luciferase reporter assay and RIP assay. DN mouse model assay was used to analyse the effect of Alisol A on renal injury of diabetic mice. RESULTS: HG treatment promoted HRMC proliferation, fibrosis, inflammation, and oxidative stress; however, these effects were reversed after Alisol A treatment. Alisol A treatment ameliorated STZ-induced renal injury of diabetic mice. Additionally, circ_0001831 or LIN28B overexpression or miR-346 downregulation relieved Alisol A-induced effects under HG conditions. Mechanistically, circ_0001831 acted as a miR-346 sponge, and LIN28B was identified as a target gene of miR-346. Further, the regulation of circ_0001831 in HG-induced HRMC dysfunction involved LIN28B. CONCLUSION: Alisol A ameliorated HG-induced HRMC fibrosis, inflammation, and oxidative stress and STZ-induced renal injury of diabetic mice by regulating the circ_0001831/miR-346/LIN28B pathway.

Association of cooking oil and incident of frailty in older adults: a cohort study.

BACKGROUND: Studies examining the potential association between cooking oil and frailty risk in older adults have produced conflicting outcomes. Therefore, our objective was to explore the relationship between cooking oil (vegetable and animal fat oils), changes in oil usage, and the risk of frailty in older adults. METHODS: We included 4,838 participants aged ≥ 65 years without frailty (frailty index < 0.25) from the 2011 wave of the Chinese Longitudinal Healthy Longevity Survey. Follow-up occurred in the 2014 and 2018 waves. Cox proportional hazard models were utilized to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) to examine the association between cooking oil and frailty. Additionally, we evaluated the effect of switching cooking oil on frailty during the follow-up period. RESULTS: During a median follow-up of 3.0 (2.8-6.9) years, 1,348 individuals (27.9%) developed frailty. Compared to those using vegetable oil, users of animal fat oil had a lower risk of frailty (HR = 0.72, 95% CI: 0.61-0.85). Participants who switched from vegetable oil to animal fat oil, as well as those consistently using animal fat oil, had lower risks of frailty with HRs of 0.70 (0.52-0.95) and 0.63 (0.51-0.77) respectively, compared to those who consistently used vegetable oil. Conversely, individuals who switched from animal fat oil to vegetable oil experienced an increased risk of frailty (HR: 1.41, 95% CI: 1.01-1.97). CONCLUSIONS: The utilization of animal fat oil in cooking exhibited a reduced frailty risk among older adults. Conversely, transitioning from animal fat oil to vegetable oil may elevate the risk. These findings propose that substituting vegetable oil with animal fat oil in the diet may safeguard against frailty.

Artificial Intelligence-Assisted Prescription Determination for Orthokeratology Lens Fitting: From Algorithm to Clinical Practice.

OBJECTIVES: To explore the potential of artificial intelligence (AI) to assist prescription determination for orthokeratology (OK) lenses. METHODS: Artificial intelligence algorithm development followed by a real-world trial. A total of 11,502 OK lenses fitting records collected from seven clinical environments covering major brands. Records were randomly divided in a three-way data split. Cross-validation was used to identify the most accurate algorithm, followed by an evaluation using an independent test data set. An online AI-assisted system was implemented and assessed in a real-world trial involving four junior and three senior clinicians. RESULTS: The primary outcome measure was the algorithm's accuracy (ACC). The ACC of the best performance of algorithms to predict the targeted reduction amplitude, lens diameter, and alignment curve of the prescription was 0.80, 0.82, and 0.83, respectively. With the assistance of the AI system, the number of trials required to determine the final prescription significantly decreased for six of the seven participating clinicians (all P <0.01). This reduction was more significant among junior clinicians compared with consultants (0.76±0.60 vs. 0.32±0.60, P <0.001). Junior clinicians achieved clinical outcomes comparable to their seniors, as 93.96% (140/149) and 94.44% (119/126), respectively, of the eyes fitted achieved unaided visual acuity no worse than 0.8 ( P =0.864). CONCLUSIONS: AI can improve prescription efficiency and reduce discrepancies in clinical outcomes among clinicians with differing levels of experience. Embedment of AI in practice should ultimately help lessen the medical burden and improve service quality for myopia boom emerging worldwide.

[Transition metal accumulation and cellular senescence].

Aging refers to a progressive decline in biological functions, leading to age-related diseases and mortality. The transition metals, including iron, copper, and manganese, play important roles in human physiological and pathological processes. Substantial research has demonstrated that senescent cells accumulate higher levels of transition metals, which in turn accelerates the process of cellular senescence and related diseases through mechanisms such as production of excessive reactive oxygen species (ROS), induction of oxidative stress, DNA damage, and mitochondrial dysfunction. This review article provides a comprehensive overview of the causes of transition metal accumulation in senescent cells, as well as the mechanisms by which it further promotes cellular senescence and related diseases. The aim is to provide insights into anti-aging and treatment of aging-related diseases caused by transition metal accumulation.

Melittin inhibits tumor cell migration and enhances cisplatin sensitivity by suppressing IL-17 signaling pathway gene LCN2 in castration-resistant prostate cancer.

BACKGROUND: Melittin is a small molecule polypeptide extracted from the abdominal cavity of bees, which is used to treat inflammatory diseases and relieve pain. However, the antitumor effect of melittin and its mechanisms remain unclear, especially in castration-resistant prostate cancer (CRPC). METHODS: Through CCK-8 assay, colony formation assay, wound healing assay and Transwell migration assay, we explored the effect of melittin on CRPC cell lines. In addition, with microarray analysis, gene ontology analysis and kyoto encyclopedia of genes and genomes analysis, this study identified key genes and signaling pathways that influence the growth of PC-3 cells. Meanwhile, the effect of melittin on CRPC was also verified through subcutaneous tumor formation experiments. Finally, we also tested the relevant indicators of human prostate cancer (PCa) specimens through immunohistochemistry and H＆E stating. RESULTS: Here, melittin was verified to inhibit the cell proliferation and migration of CPRC. Moreover, RNA-sequence analysis demonstrated that Interleukin-17 (IL-17) signaling pathway gene Lipocalin-2 (LCN2) was downregulated by melittin treatment in CRPC. Further investigation revealed that overexpression of LCN2 was able to rescue tumor suppression and cisplatin sensitivity which melittin mediated. Interestingly, the expression of LCN2 is highly related to metastasis in PCa. CONCLUSIONS: In brief, our study indicates that LCN2 plays an oncogenic role in CRPC and melittin may be selected as an attractive candidate for CRPC therapy.

Statins for the Treatment of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: A Systematic Review and Meta-Analysis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has become more common as a result of changes in dietary structure and lifestyle. It is now the most common chronic liver disease both in China and in the rest of the world (NAFLD is also of concern in European and American countries). STUDY QUESTION: NAFLD and nonalcoholic steatohepatitis (NASH) are different stages of fatty liver disease. There is currently a lack of consensus on the use of statin therapy. We conducted a meta-analysis to evaluate the efficacy of statins in the treatment of NAFLD and NASH. DATA SOURCES: PubMed, MEDLINE, and other literature databases, including the Cochrane Library, were searched. STUDY DESIGN: The primary inclusion criteria for studies included the use of different statins for the treatment of NAFLD and NASH. Two reviewers identified documents and extracted data based on predetermined inclusion and exclusion criteria. To examine heterogeneity and publication bias, all analyses were undertaken using the complete meta-analysis Review Manager 5.3 software. RESULTS: The meta-analysis includes 4 randomized controlled studies involving 169 participants with NAFLD and NASH. In comparison with the control group, statins dramatically lowered serum levels of aspartate transaminase, alanine aminotransferase (ALT), triglycerides, and cholesterol. CONCLUSIONS: The use of statins in the treatment of NAFLD and NASH has shown significant histological and biochemical benefits, especially in patients with hyperlipidemia. To assess the effects of statins on NAFLD and NASH, more large research and randomized placebo-controlled trials are needed.

Gender differences in metabolic syndrome and its components in southern china using a healthy lifestyle index: a cross-sectional study.

BACKGROUND: Lifestyle changes are important for the prevention and management of metabolic syndrome (MetS), but studies that focus on gender differences in the lifestyle risk factors of MetS are limited in China. This research aimed to generate a healthy lifestyle index (HLI) to assess the behavioral risk factors of MetS and its components, and to explore the gender differences in HLI score and other influencing factors of MetS. METHODS: A convenience sample of 532 outpatients were recruited from a general hospital in Changsha, China. The general information and HLI scores [including physical activity (PA), diet, smoking, alcohol use, and body mass index (BMI)] of the subjects were collected through questionnaires, and each patient's height, weight, waist circumference, and other physical signs were measured. Logistic regression analysis was used to analyze the risk factors of MetS and its components. RESULTS: The prevalence of MetS was 33.3% for the whole sample (46.3% in males and 23.3% in females). The risk of MetS increased with age, smoking, unhealthy diet, and BMI in males and with age and BMI in females. Our logistic regression analysis showed that lower HLI (male: OR = 0.838,95%CI = 0.757-0.929; female: OR = 0.752, 95%CI = 0.645-0.876) and older age (male: OR = 2.899, 95%CI = 1.446-5.812; female: OR = 4.430, 95%CI = 1.640-11.969) were independent risk factors of MetS, for both sexes. CONCLUSION: Low levels of HLI and older ages were independent risk factors of MetS in both males and females. The association between aging and MetS risk was stronger in females, while the association between unhealthy lifestyles and MetS risk was stronger in males. Our findings reinforced the expected gender differences in MetS prevalence and its risk factors, which has implications for the future development of gender-specific MetS prevention and intervention programs.

HSF1 inhibition attenuates HIV-1 latency reversal mediated by several candidate LRAs In Vitro and Ex Vivo.

HIV-1 latency is a major barrier to cure. Identification of small molecules that destabilize latency and allow immune clearance of infected cells could lead to treatment-free remission. In vitro models of HIV-1 latency involving cell lines or primary cells have been developed for characterization of HIV-1 latency and high-throughput screening for latency-reversing agents (LRAs). We have shown that the majority of LRAs identified to date are relatively ineffective in cells from infected individuals despite activity in model systems. We show here that, for diverse LRAs, latency reversal observed in model systems involves a heat shock factor 1 (HSF1)-mediated stress pathway. Small-molecule inhibition of HSF1 attenuated HIV-1 latency reversal by histone deactylase inhibitors, protein kinase C agonists, and proteasome inhibitors without interfering with the known mechanism of action of these LRAs. However, latency reversal by second mitochondria-derived activator of caspase (SMAC) mimetics was not affected by inhibition of HSF1. In cells from infected individuals, inhibition of HSF1 attenuated latency reversal by phorbol ester+ionomycin but not by anti-CD3+anti-CD28. HSF1 promotes elongation of HIV-1 RNA by recruiting P-TEFb to the HIV-1 long terminal repeat (LTR), and we show that inhibition of HSF1 attenuates the formation of elongated HIV-1 transcripts. We demonstrate that in vitro models of latency have higher levels of the P-TEFb subunit cyclin T1 than primary cells, which may explain why many LRAs are functional in model systems but relatively ineffective in primary cells. Together, these studies provide insights into why particular LRA combinations are effective in reversing latency in cells from infected individuals.

Knowledge, attitudes, and practice of Endocrinology healthcare workers regarding screening for pre-ulcerative diabetic foot lesions.

OBJECTIVE: To investigate knowledge, attitude and practice of screening pre-ulcerative lesions among endocrinology healthcare workers. METHODS: A new questionnaire was developed and distributed online and 1004 valid questionnaires were returned. T-test, ANOVA, Pearson correlation analysis, and multiple linear regression were used for statistical analysis. RESULTS: A total of 1100 questionnaires were returned, and 96 were excluded. The scores of endocrinology healthcare workers' knowledge, attitude, and practice for screening for pre-ulcerative lesions were 45.46 ± 16.26, 92.11 ± 10.50, and 72.27 ± 17.63 respectively. 60.2% participants had been trained to screen for pre-ulcerative lesions, but 39.8% had not been trained. 31.8% of healthcare professionals claimed that their hospital did not have a screening project for pre-ulcer diabetic foot lesions. Positive relationships were found between knowledge and practice and between attitude and practice. Multiple linear regression analysis showed that: level II hospital and tertiary hospital were the main factors influencing the knowledge scores; Undergraduate and participating in relevant training were the main factors influencing the attitude scores; participating in relevant training, hospital conducts relevant projects, and patient cooperation, and working hours were the main factors influencing the practice score. CONCLUSIONS: Endocrinology healthcare workers need more knowledge regarding pre-ulcerative lesions, and their screening practices need to be strengthened. Increased education and training for pre-ulcerative lesion screening should be implemented among healthcare workers in endocrinology departments.

How sandbag-able are concussion sideline assessments? A close look at eye movements to uncover strategies.

Background: Sideline diagnostic tests for concussion are vulnerable to volitional poor performance ("sandbagging") on baseline assessments, motivated by desire to subvert concussion detection and potential removal from play. We investigated eye movements during sandbagging versus best effort on the King-Devick (KD) test, a rapid automatized naming (RAN) task.Methods: Participants performed KD testing during oculography following instructions to sandbag or give best effort.Results: Twenty healthy participants without concussion history were included (mean age 27 ± 8 years). Sandbagging resulted in longer test times (89.6 ± 39.2 s vs 48.2 ± 8.5 s, p < .001), longer inter-saccadic intervals (459.5 ± 125.4 ms vs 311.2 ± 79.1 ms, p < .001) and greater numbers of saccades (171.4 ± 47 vs 138 ± 24.2, p < .001) and reverse saccades (wrong direction for reading) (21.2% vs 11.3%, p < .001). Sandbagging was detectable using a logistic model with KD times as the only predictor, though more robustly detectable using eye movement metrics.Conclusions: KD sandbagging results in eye movement differences that are detectable by eye movement recordings and suggest an invalid test score. Objective eye movement recording during the KD test shows promise for distinguishing between best effort and post-injury performance, as well as for identifying sandbagging red flags.

Detection of normal and slow saccades using implicit piecewise polynomial approximation.

The quantitative analysis of saccades in eye movement data unveils information associated with intention, cognition, and health status. Abnormally slow saccades are indicative of neurological disorders and often imply a specific pathological disturbance. However, conventional saccade detection algorithms are not designed to detect slow saccades, and are correspondingly unreliable when saccades are unusually slow. In this article, we propose an algorithm that is effective for the detection of both normal and slow saccades. The proposed algorithm is partly based on modeling saccadic waveforms as piecewise-quadratic signals. The algorithm first decreases noise in acquired eye-tracking data using optimization to minimize a prescribed objective function, then uses velocity thresholding to detect saccades. Using both simulated saccades and real saccades generated by healthy subjects and patients, we evaluate the performance of the proposed algorithm and 10 other detection algorithms. We show the proposed algorithm is more accurate in detecting both normal and slow saccades than other algorithms.

Development and Clinical Uses of a Mobile Application for Smart Wound Nursing Management.

OBJECTIVE: Establishing a smart platform for wound nursing management is imperative to accelerating the development of this specialty. A mobile application (app) was created based on the clinical needs of wound care to improve working efficiency and wound management, as well as enable information sharing and categorical retrieval of patient records. METHODS: Supported by the National Mobile Laboratory of China, the authors' wound care center collaborated with information technology engineers and user interface designers to establish a multidisciplinary team of experts in wound nursing information management and develop a digital app. Electronic tablets were chosen as a convenient clinical method to collect complete information in a standardized format. In the app, case records are synchronously cataloged for rapid retrieval. The app was designed such that practicing nurses could quickly learn how to use the various functions of the app. Through constant iterative optimization, the relevant functional modules have been further improved. RESULTS AND CONCLUSIONS: After a 1-year clinical trial, app functions have stabilized, fulfilling the expectations of technicians and boosting the operating efficiency of clinical practices. In comparison with traditional methods, the app allows for easy access to patient information; rapidly reviewed, synchronous cataloguing; and convenient retrieval. Further exploration is warranted.

Application of "family member-like" care strategies among COVID-19 patients in an isolation ward. / "家属"ç §æŠ¤ç­–ç•¥åœ¨éš”ç¦»ç— æˆ¿çš„2019å† çŠ¶ç— æ¯’ç— æ‚£è€ ä¸­çš„åº”ç”¨.

OBJECTIVES: To control the pandemic of coronavirus disease 2019 (COVID-19) effectively, strict isolation measures have been taken in China. Suspected patients must be isolated, and the confirmed patients specifically are isolated in negative-pressure isolation rooms. During the isolation, patients face difficulty in adapting to their surrounding environment, worry about the prognosis of the disease, lack confidence in treatment, separate from their families, and have a sense of distance from medical staff. Isolated patients may possess the feelings of negativity, including loneliness, anxiety, depression, insomnia, and despair. Hence, to reduce the risk of adverse psychological outcomes, "family member-like" care strategies were developed and implemented to solve problems associated with the COVID-19 pandemic. This study aims to examine whether using "family member-like" care strategies can improve psychological resilience and reduce depression, anxiety, and stress symptoms among patients with COVID-19 in an isolation ward. METHODS: A quasi-experimental design was used to evaluate the "family member-like" care strategies for adult patients with COVID-19 in an isolation ward. COVID-19 patients in the Xiangya ward of the West District of the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology in Wuhan, Hubei province, were included in this study from February 9 to March 20, 2020. Healthcare providers who volunteered as family members were assigned to patients. They practiced one-to-one care and provided continuous and whole care for the patients who were from admission to discharge. Connor-Davidson Resilience Scale-10 (CD-RISC-10) and Depression Anxiety Stress Scale-21 (DASS-21) were used to evaluate the resilience and psychological status of COVID-19 inpatients upon hospital admission, 2 weeks after admission, and at their discharge from the hospital. RESULTS: The questionnaire response rate of the "family member-like" strategies was 100%. Of the 60 patients, 39 (65.0%) were male, and 21 (35%) were female. The hospital stay was (27.5±3.5) days. All the 60 patients were cured and discharged without any death and serious complications. The total scores for CD-RISC were 8.83±6.86 at admission, 29.13±5.42 at 2 weeks after admission, and 33.87±6.14 at discharge, which were significantly improved at the 2 follow-ups (F=404.564, P<0.001). Multivariate analysis and repeated measurements also indicated that patients experienced significant improvements in tenacity (F=360.839, P<0.001), strength (F=368.217, P<0.001), and optimism (F=328.456, P<0.001) at the 2 follow-ups. The total scores of DASS-21 were 49.27±11.30 at admission, 30.77±16.71 at 2 weeks after admission, and 4.17±11.03 at discharge, and the scores were significantly decreased at the 2 follow-ups (F=270.536, P<0.001). Multivariate analysis and repeated measurements also indicated that patients experienced significant decreases in depression (F=211.938, P<0.001), anxiety (F=285.592, P<0.001), and stress (F=287.478, P<0.001) at the 2 follow-ups. CONCLUSIONS: "Family member-like" strategies had positive effects on improving psychological resilience and reducing the symptoms of anxiety and depression of COVID-19 patients. It might be an effective care method for COVID-19 patients. It should be incorporated into emergency care management to improve care quality during public health emergencies of infectious diseases.

Experimental composable security decoy-state quantum key distribution using time-phase encoding.

Quantum key distribution (QKD) promises provably secure communications. In order to improve the secret key rate, combining a biased basis choice with the decoy-state method is proposed. Concomitantly, there is a basis-independent detection efficiency condition, which usually cannot be satisfied in a practical system, such as the time-phase encoding. Fortunately, this flaw has been recently removed theoretically and experimentally in the four-intensity decoy-state BB84 QKD protocol using the fact that the expected yields of single-photon states prepared in two bases stay the same for a given measurement basis. However, the security proofs do not fully consider the finite-key effects for general attacks. In this work, we provide the rigorous finite-key security bounds in the universally composable framework for the four-intensity decoy-state BB84 QKD protocol. We build a time-phase encoding system with 200 MHz clock to implement this protocol, in which the real-time secret key rate is more than 60 kbps over 50 km single-mode fiber.

ATF4-Mediated Upregulation of REDD1 and Sestrin2 Suppresses mTORC1 Activity during Prolonged Leucine Deprivation.

BACKGROUND: The protein kinase target of rapamycin (mTOR) in complex 1 (mTORC1) is activated by amino acids and in turn upregulates anabolic processes. Under nutrient-deficient conditions, e.g., amino acid insufficiency, mTORC1 activity is suppressed and autophagy is activated. Intralysosomal amino acids generated by autophagy reactivate mTORC1. However, sustained mTORC1 activation during periods of nutrient insufficiency would likely be detrimental to cellular homeostasis. Thus, mechanisms must exist to prevent amino acids released by autophagy from reactivating the kinase. OBJECTIVE: The objective of the present study was to test whether mTORC1 activity is inhibited during prolonged leucine deprivation through ATF4-dependent upregulation of the mTORC1 suppressors regulated in development and DNA damage response 1 (REDD1) and Sestrin2. METHODS: Mice (8 wk old; C57Bl/6 × 129SvEV) were food deprived (FD) overnight and one-half were refed the next morning. Mouse embryo fibroblasts (MEFs) deficient in ATF4, REDD1, and/or Sestrin2 were deprived of leucine for 0-16 h. mTORC1 activity and ATF4, REDD1, and Sestrin2 expression were assessed in liver and cell lysates. RESULTS: Refeeding FD mice resulted in activation of mTORC1 in association with suppressed expression of both REDD1 and Sestrin2 in the liver. In cells in culture, mTORC1 exhibited a triphasic response to leucine deprivation, with an initial suppression followed by a transient reactivation from 2 to 4 h and a subsequent resuppression after 8 h. Resuppression occurred concomitantly with upregulated expression of ATF4, REDD1, and Sestrin2. However, in cells lacking ATF4, neither REDD1 nor Sestrin2 expression was upregulated by leucine deprivation, and resuppression of mTORC1 was absent. Moreover, in cells lacking either REDD1 or Sestrin2, mTORC1 resuppression was attenuated, and in cells lacking both proteins resuppression was further blunted. CONCLUSIONS: The results suggest that leucine deprivation upregulates expression of both REDD1 and Sestrin2 in an ATF4-dependent manner, and that upregulated expression of both proteins is involved in resuppression of mTORC1 during prolonged leucine deprivation.