Expanded encyclopaedias of DNA elements in the human and mouse genomes.

The human and mouse genomes contain instructions that specify RNAs and proteins and govern the timing, magnitude, and cellular context of their production. To better delineate these elements, phase III of the Encyclopedia of DNA Elements (ENCODE) Project has expanded analysis of the cell and tissue repertoires of RNA transcription, chromatin structure and modification, DNA methylation, chromatin looping, and occupancy by transcription factors and RNA-binding proteins. Here we summarize these efforts, which have produced 5,992 new experimental datasets, including systematic determinations across mouse fetal development. All data are available through the ENCODE data portal (https://www.encodeproject.org), including phase II ENCODE1 and Roadmap Epigenomics2 data. We have developed a registry of 926,535 human and 339,815 mouse candidate cis-regulatory elements, covering 7.9 and 3.4% of their respective genomes, by integrating selected datatypes associated with gene regulation, and constructed a web-based server (SCREEN; http://screen.encodeproject.org) to provide flexible, user-defined access to this resource. Collectively, the ENCODE data and registry provide an expansive resource for the scientific community to build a better understanding of the organization and function of the human and mouse genomes.

The FLOWERING LOCUS T 5b positively regulates photoperiodic flowering and improves the geographical adaptation of soybean.

Plants can sense the photoperiod to flower at the right time. As a sensitive short-day crop, soybean (Glycine max) flowering varies greatly depending on photoperiods, affecting yields. Adaptive changes in soybeans rely on variable genetic loci such as E1 and FLOWERING LOCUS T orthologs. However, the precise coordination and control of these molecular components remain largely unknown. In this study, we demonstrate that GmFT5b functions as a crucial factor for soybean flowering. Overexpressed or mutated GmFT5b resulted in significantly early or later flowering, altering expression profiles for several downstream flowering-related genes under a long-day photoperiod. GmFT5b interacts with the transcription factor GmFDL15, suggesting transcriptional tuning of flowering time regulatory genes via the GmFT5b/GmFDL15 complex. Notably, GmFT5a partially compensated for GmFT5b function, as ft5a ft5b double mutants exhibited an enhanced late-flowering phenotype. Association mapping revealed that GmFT5b was associated with flowering time, maturity, and geographical distribution of soybean accessions, all associated with the E1 locus. Therefore, GmFT5b is a valuable target for enhancing regional adaptability. Natural variants or multiple mutants in this region can be utilized to generate optimized soybean varieties with precise flowering times.

Protein profiles reveal MSH6/MSH2 as a potential biomarker for hepatocellular carcinoma with microvascular invasion.

AIM: Microvascular invasion (MVI) is an independent risk factor for postoperative recurrence and metastasis in hepatocellular carcinoma (HCC). However, the specific protein expression profiles that differentiate HCC with MVI from those without MVI remain unclear. METHODS: The profiles of proteins in early-stage HCC tissues and normal liver tissues were characterized by quantitative proteomics techniques. Immunohistochemical (IHC) staining was undertaken on tissue microarrays from 80 HCC patients to assess the expression of MSH2 and MSH6. Cell counting, colony formation, migration, and invasion assays were carried out in vitro. RESULTS: We identified 5164 proteins in both HCC tissues and adjacent normal liver tissues. Compared to HCC without MVI, 148 upregulated proteins and 97 downregulated proteins were found in HCC with MVI. Particularly noteworthy was the remarkable upregulation of MSH6/MSH2 among these dysregulated proteins in HCC with MVI. Further validation through bioinformatics prediction and IHC confirmed the elevated expression of MSH6/MSH2, which correlated with aggressive disease characteristics and poor prognosis. Receiver operating characteristic curve analyses revealed a substantial area under the curve of 0.761 (specificity 71.79%, sensitivity 73.17%) for the combined use of MSH6/MSH2. Knockdown of MSH6/MSH2 significantly inhibited HCC cell proliferation and invasion in vitro. CONCLUSIONS: Our study establishes MSH6 or MSH2 as an oncogene that is prominently overexpressed during HCC progression, which provides new targets for HCC with MVI.

Clinical application of repetitive transcranial magnetic stimulation in improving functional impairments post-stroke: review of the current evidence and potential challenges.

In recent years, the stroke incidence has been increasing year by year, and the related sequelae after stroke, such as cognitive impairment, motor dysfunction, and post-stroke depression, seriously affect the patient's rehabilitation and daily activities. Repetitive transcranial magnetic stimulation (rTMS), as a safe, non-invasive, and effective new rehabilitation method, has been widely recognized in clinical practice. This article reviews the application and research progress of rTMS in treating different functional impairments (cognitive impairment, motor dysfunction, unilateral spatial neglect, depression) after stroke in recent years, and preliminary summarized the possible mechanisms. It has been found that the key parameters that determine the effectiveness of rTMS in improving post-stroke functional impairments include pulse number, stimulated brain areas, stimulation intensity and frequency, as well as duration. Generally, high-frequency stimulation is used to excite the ipsilateral cerebral cortex, while low-frequency stimulation is used to inhibit the contralateral cerebral cortex, thus achieving a balance of excitability between the two hemispheres. However, the specific mechanisms and the optimal stimulation mode for different functional impairments have not yet reached a consistent conclusion, and more research is needed to explore and clarify the best way to use rTMS. Furthermore, we will identify the issues and challenges in the current research, explore possible mechanisms to deepen understanding of rTMS, propose future research directions, and offer insightful insights for better clinical applications.

Increased serum methylmalonic acid levels were associated with the presence of cognitive dysfunction in older chronic kidney disease patients with albuminuria.

BACKGROUND: This study aimed to evaluate the correlation between serum methylmalonic acid (MMA) levels and cognition function in patients with chronic kidney disease (CKD). METHODS: In this cross-sectional study, we included 537 CKD individuals aged ≥ 60-year-old with albuminuria from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Four cognitive tests including the Digit Symbol Substitution Test (DSST), the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Delayed Recall and Word Learning tests, and the Animal Fluency test (AF) were performed. Associations between MMA and cognition scores were assessed with linear regression models. RESULTS: MMA level was negatively associated with residual renal function and nutrition status. After multivariate adjustment, elevated serum MMA levels were independently correlated with decline of cognition in CKD patients with albuminuria. CONCLUSION: Our study showed that higher serum MMA levels were independently associated with the presence of cognition dysfunction in CKD patients. The exact pathogenesis of MMA and cognition needs further research.

Sex-specific associations between body mass index trajectories and risk of hypertension.

BACKGROUND: Although it is well established that obesity is a risk factor for hypertension, the effect of distinct long-term patterns of body mass index (BMI) on blood pressure (BP) in later life is poorly understood. METHODS: Based on the China Health and Nutrition Survey, we analyzed 2920 participants aged 3-17 years with initial normal BP at baseline (1991-2011), who were followed up for the development of hypertension (1993-2015). The group-based trajectory model was applied to identify BMI trajectories, and Cox regression was used to assess their associations with hypertension risk. Stratified analyses were conducted to explore differences across subgroups. RESULTS: During an average follow-up time of 11.20 (7.69) years for males and 7.20 (5.21) years for females, 339 males and 212 females were identified with hypertension, respectively. Three BMI trajectories were identified: low-increasing (60.58% of males and 73.03% of females), moderate-increasing (33.08% of males and 24.22% of females), and high-increasing (6.34% of males and 2.76% of females). Our study found a significant positive association between a higher BMI trajectory and hypertension risk in males (all P for trend < 0.05). Specifically, males in the high-increasing BMI group had a higher risk of hypertension compared with those in the low-increasing group (HR = 1.76, 95% CI: 1.04-2.97). Stratified analyses revealed stronger associations among smokers, drinkers, and inactive individuals. CONCLUSION: Our findings suggest that maintaining a normal BMI and healthy lifestyle from childhood may lower subsequent risk of hypertension.

Rapid diagnosis and tumor margin assessment during pancreatic cancer surgery with the MasSpec Pen technology.

Intraoperative delineation of tumor margins is critical for effective pancreatic cancer surgery. Yet, intraoperative frozen section analysis of tumor margins is a time-consuming and often challenging procedure that can yield confounding results due to histologic heterogeneity and tissue-processing artifacts. We have previously described the development of the MasSpec Pen technology as a handheld mass spectrometry-based device for nondestructive tissue analysis. Here, we evaluated the usefulness of the MasSpec Pen for intraoperative diagnosis of pancreatic ductal adenocarcinoma based on alterations in the metabolite and lipid profiles in in vivo and ex vivo tissues. We used the MasSpec Pen to analyze 157 banked human tissues, including pancreatic ductal adenocarcinoma, pancreatic, and bile duct tissues. Classification models generated from the molecular data yielded an overall agreement with pathology of 91.5%, sensitivity of 95.5%, and specificity of 89.7% for discriminating normal pancreas from cancer. We built a second classifier to distinguish bile duct from pancreatic cancer, achieving an overall accuracy of 95%, sensitivity of 92%, and specificity of 100%. We then translated the MasSpec Pen to the operative room and predicted on in vivo and ex vivo data acquired during 18 pancreatic surgeries, achieving 93.8% overall agreement with final postoperative pathology reports. Notably, when integrating banked tissue data with intraoperative data, an improved agreement of 100% was achieved. The result obtained demonstrate that the MasSpec Pen provides high predictive performance for tissue diagnosis and compatibility for intraoperative use, suggesting that the technology may be useful to guide surgical decision-making during pancreatic cancer surgeries.

Yi-Shen-Hua-Shi regulates intestinal microbiota dysbiosis and protects against proteinuria in patients with chronic kidney disease: a randomized controlled study.

CONTEXT: Yi-Shen-Hua-Shi (YSHS) is a traditional Chinese medicine that treats chronic kidney disease (CKD). However, its efficacy in reducing proteinuria and underlying mechanisms is unknown. OBJECTIVE: This single-center randomized controlled trial explored whether YSHS could improve proteinuria and modulate the gut microbiota. MATERIALS AND METHODS: 120 CKD patients were enrolled and randomized to receive the renin-angiotensin-aldosterone system (RAAS) inhibitor plus YSHS (n = 56) or RAAS inhibitor (n = 47) alone for 4 months, and 103 patients completed the study. We collected baseline and follow-up fecal samples and clinical outcomes from participants. Total bacterial DNA was extracted, and the fecal microbiome was analyzed using bioinformatics. RESULTS: Patients in the intervention group had a significantly higher decrease in 24-h proteinuria. After 4 months of the YSHS intervention, the relative abundance of bacteria that have beneficial effects on the body, such as Faecalibacterium, Lachnospiraceae, Lachnoclostridium, and Sutterella increased significantly, while pathogenic bacteria such as the Eggerthella and Clostridium innocuum group decreased. However, we could not find these changes in the control group. Redundancy analysis showed that the decline in 24-h proteinuria during follow-up was significantly correlated with various taxa of gut bacteria, such as Lachnospiraceae and the Lachnoclostridium genus in the YSHS group. KEGG analysis also showed the potential role of YSHS in regulating glycan, lipid, and vitamin metabolism. DISCUSSION AND CONCLUSION: The YSHS granule reduced proteinuria associated with mitigating intestinal microbiota dysbiosis in CKD patients. The definite mechanisms of YSHS to improve proteinuria need to be further explored. TRIAL REGISTRATION: ChiCTR2300076136, retrospectively registered.

Acupuncture for chemotherapy-associated insomnia in breast cancer patients: an assessor-participant blinded, randomized, sham-controlled trial.

BACKGROUND: Insomnia is a highly prevalent symptom occurred during and post-chemotherapy. Acupuncture may have beneficial effects in the management of chemotherapy-associated insomnia. This study was conducted to determine the efficacy and safety of acupuncture in improving chemotherapy-associated insomnia in breast cancer patients. METHODS: This assessor-participant blinded, randomized, sham-controlled trial was conducted from November 2019 to January 2022 (follow-up completed July 2022). Participants were referred by oncologists from two Hong Kong hospitals. Assessments and interventions were conducted at the outpatient clinic of School of Chinese Medicine, the University of Hong Kong. The 138 breast cancer patients with chemotherapy-associated insomnia were randomly assigned to receive either 15 sessions of active acupuncture regimen by combining needling into body acupoints and acupressure on auricular acupoints or sham acupuncture control (69 each) for 18 weeks, followed by 24 weeks of follow-up. The primary outcome was measured using Insomnia Severity Index (ISI). Secondary outcomes included the Pittsburgh Sleep Quality Index, Actiwatch and sleep diary for sleep parameters, depression and anxiety, fatigue and pain, and quality of life. RESULTS: There were 87.7% (121/138) participants who completed the primary endpoint (week-6). The active acupuncture regimen was not superior to the sham control in reducing ISI score from baseline to 6 weeks (mean difference: - 0.4, 95% CI - 1.8-1.1; P = 0.609), but produced short-term treatment and long-term follow-up better outcomes in improving sleep onset latency, total sleep time, sleep efficiency, anxiety, depression, and quality of life. Participants of the active acupuncture group had a pronouncedly higher cessation rate of sleeping medications than the sham control (56.5% vs. 14.3%, P = 0.011). All treatment-related adverse events were mild. No participants discontinued treatments due to adverse events. CONCLUSION: The active acupuncture regimen could be considered as an effective option for the management of chemotherapy-associated insomnia. It also could serve as a tapering approach to reduce and even replace the use of sleeping medications in breast cancer patients. Trial registration Clinicaltrials.gov : NCT04144309. Registered 30 October 2019.

Prevalence and risk factors of long COVID 6-12 months after infection with the Omicron variant among nonhospitalized patients in Hong Kong.

Long COVID has been reported among patients with COVID-19, but little is known about the prevalence and risk factors associated with long COVID 6-12 months after infection with the Omicron variant. This is a large-scale retrospective study. A total of 6242 out of 12 950 nonhospitalized subjects of all ages with SARS-CoV-2 infection (confirmed by polymerase chain reaction/rapid antigen test) during the Omicron dominant outbreak (December 31, 2021-May 6, 2022) in Hong Kong were included. Prevalence of long COVID, frequencies of symptoms, and risk factors were analyzed. Three thousand four hundred and thirty (55.0%) subjects reported at least one long COVID symptom. The most reported symptom was fatigue (1241, 36.2%). Female gender, middle age, obesity, comorbidities, vaccination after infection, having more symptoms, and presenting fatigue/chest tightness/headache/diarrhea in the acute stage of illness were identified as associated risk factors for long COVID. Patients who had received three or more doses of vaccine were not associated with a lower risk of long COVID (adjusted odds ratio 1.105, 95% confidence interval 0.985-1.239, p = 0.088). Among patients with at least three doses of vaccine, there was no significant difference in the risk of long COVID between the CoronaVac vaccine and BNT162b2 vaccine (p > 0.05). Omicron infection can lead to long COVID in a significant proportion of nonhospitalized patients 6-12 months after infection. Further investigation is needed to uncover the mechanisms underlying the development of long COVID and determine the impact of various risk factors such as vaccines.

Weekly symptom profiles of nonhospitalized individuals infected with SARS-CoV-2 during the Omicron outbreak in Hong Kong: A retrospective observational study from a telemedicine center.

Omicron BA.2.2 is the dominant variant in the Hong Kong outbreak since December 31, 2021. There is no study reporting the weekly symptom profile after infection. In this retrospective study, participants who tested positive for SARS-CoV-2 after December 31, 2021, and registered in the telemedicine system between March 14 and May 6, 2022, were analyzed. Among registered 12 950 self-quarantined COVID-19-positive patients, 11 776 symptomatic patients were included for weekly symptom profile analysis. A total of 4718 (40.1%) patients reported symptoms in the first week after a positive test, 2501 (21.2%) in the second week, 1498 (12.7%) in the third week, 1048 (8.9%) in the fourth week, and 2011 (17.1%) in over 4 weeks. Cough was the most common symptom in all participants. Patients in the first week had higher odds of reporting fever (0.206, 95% confidence interval [CI]: 0.161-0.263, p < 0.001) and sore throat (0.228, 95% CI: 0.208-0.252, p < 0.001). Patients in over 4 weeks had higher odds of reporting fatigue (1.263, 95% CI: 1.139-1.402, p < 0.001). Further, having at least two vaccine doses linked to lower odds of having fever (0.675, 95% CI: 0.562-0.811, p < 0.001), but not associated with the presence of cough and fatigue. Diabetic patients had higher odds of reporting diarrhea (1.637, 95% CI: 1.351-1.982, p < 0.001). Symptoms from Omicron infection may last for more than 4 weeks and symptom profiles vary from week to week. Vaccination and comorbidity affect the symptom profiles.

RING finger E3 ubiquitin ligase gene TaAIRP2-1B controls spike length in wheat.

E3 ubiquitin ligase genes play important roles in the regulation of plant development. They have been well studied in plants, but have not been sufficiently investigated in wheat. Here, we identified a highly expressed RING finger E3 ubiquitin ligase gene TaAIRP2-1B (ABA-insensitive RING protein 2) in wheat spike. Sequence polymorphism and association analysis showed that TaAIRP2-1B is significantly associated with spike length under various conditions. The genotype with haplotype Hap-1B-1 of TaAIRP2-1B has a longer spike than that of Hap-1B-2, and was positively selected in the process of wheat breeding in China. Moreover, the TaAIRP2-1B-overexpressing rice lines have longer panicles compared with wild-type plants. The expression levels of TaAIRP2-1B in Hap-1B-1 accessions were higher than in Hap-1B-2 accessions. Further study revealed that the expression of TaAIRP2-1B was negatively regulated by TaERF3 (ethylene-responsive factor 3) via binding to the Hap-1B-2 promoter, but not via binding of Hap-1B-1. Additionally, several candidate genes interacting with TaAIRP2-1B were obtained by screening the cDNA library of wheat in yeast cells. It was found that TaAIRP2-1B interacted with TaHIPP3 (heavy metal-associated isoprenylated protein 3) and promoted TaHIPP3 degradation. Our study demonstrates that TaAIRP2-1B controls spike length, and the haplotype Hap-1B-1 of TaAIRP2-1B is a favorable natural variation for spike length enhancement in wheat. This work also provides genetic resources and functional markers for wheat molecular breeding.

Minocycline, a classic antibiotic, exerts psychotropic effects by normalizing microglial neuroinflammation-evoked tryptophan-kynurenine pathway dysregulation in chronically stressed male mice.

The dysregulation of tryptophan-kynurenine pathway (TKP) is extensively involved in the pathophysiology of Alzheimer's disease, depression, and neurodegenerative disorders. Minocycline, a classic antibiotic, may exert psychotropic effects associated with the modulation of TKP. In this study, we examined the effects of minocycline in improving behaviour and modulating TKP components in chronically stressed male mice. Following repeated treatment with 22.5 mg/kg and 45 mg/kg minocycline for 27 days, the stressed mice particularly with higher dose displayed significant improvement on cognitive impairment, depression- and anxiety-like behaviour. Minocycline suppressed stress-induced overexpression of pro-inflammatory cytokines and restored anti-inflammatory cytokines. Chronic stress dramatically suppressed blood and prefrontal cortical levels of the primary substrate tryptophan (TRP), the neuroprotective metabolite kynurenic acid (KYNA), and KYNA/KYN ratio, but increased the intermediate kynurenine (KYN), 3-hydroxykynurenine (3-HK), KYN/TRP ratio, and the neurotoxic metabolite quinolinic acid (QUIN). Minocycline partially or completely reversed changes in these components. Minocycline also inhibited stress-induced overexpression of QUIN-related enzymes, indoleamine 2, 3-dioxygenase 1(iDO-1), kynureninase (KYNU), kynurenine 3-monooxygenase (KMO), 3-hydroxyanthranilate 3,4-dioxygenase (3-HAO), but rescued the decreased expression of kynurenine aminotransferase (KAT) in brain regions. Behavioral improvements were correlated with multiple TKP metabolites and enzymes. These results suggest that the psychotropic effects of minocycline are mainly associated with the restoration of biodistribution of the primary substrate in the brain and normalization of neuroinflammation-evoked TKP dysregulation.

Prognostic value of red cell distribution width and mean corpuscular volume on mortality in hemodialysis patients.

BACKGROUND: Anemia is a common consequence of chronic kidney disease (CKD). Red cell distribution width (RDW) and mean corpuscular volume (MCV) are principally used for differential diagnosis of anemia. Limited evidence is available for its prognostic value for mortality in hemodialysis (HD) patients. We aimed to definite the relationship between RDW and MCV and mortality in HD patients. METHOD: This cohort study examined all-cause and cardiovascular (CV) mortality with 181 maintenance HD patients from February 2015. Patients were divided into four groups according to the median of RDW and MCV. Pearson analysis was conducted to determine the related factors of RDW and MCV. The independent association of RDW and MCV with mortality was examined with Kaplan-Meier curve and Cox regression analysis. RESULTS: This study included 181 HD patients for a median follow-up of 71 months. We found RDW was positively related to neutrophil count, C-reaction protein, and ferritin, while negatively related to hemoglobin, albumin, and creatinine. Only neutrophil count and ferritin were significantly related to MCV in this study. In the multivariate Cox regression analysis, the high RDW group was associated with higher risk of all-cause mortality (odds ratio, 3.787; 95% confidence interval, 1.037 to 13.834; p = 0.044). The relationship between RDW and MCV and CV mortality was not significant. CONCLUSIONS: RDW could emerge as an additive risk factor for all-cause mortality in maintenance HD patients, independent of other factors. An absolute value of MCV to predict mortality and the underlying pathophysiologic mechanisms should be confirmed in the future.

Phospholipase A2 Receptor Antibodies and Clinical Prognosis in Patients with Idiopathic Membranous Nephropathy: An Updated Systematic Review and Meta-Analysis.

BACKGROUND: Idiopathic membranous nephropathy (IMN) is the most common form of primary nephrotic syndrome in adults. Antibodies against the M-type phospholipase A2 receptor (PLA2R-ab) are considered as diagnostic biomarkers of IMN. OBJECTIVE: Here, we performed an updated meta-analysis to assess the diagnostic value of PLA2R-ab for clinical remission in IMN patients. METHOD: PubMed, Embase, and Cochrane databases were searched for relevant studies published before September 2022. Odds ratios and corresponding 95% confidence intervals were determined using a fixed or random effects model. The heterogeneity among studies was explored by subgroup analysis. RESULTS: Sixteen studies involving 1,761 IMN participants were included. There were significant differences between PLA2R-ab (+) and PLA2R-ab (-) patients in terms of complete remission (CR) and spontaneous remission. The rates of partial remission (PR) and relapse were similar between the two groups. Patients with PLA2R-ab (-) were at a higher CR rate when treated with a calcineurin inhibitor or a treatment course for 3 months and 6 months, while the spontaneous remission rate was higher in PLA2R-ab seronegative patients from Asia. However, the CR and spontaneous remission rate only significantly declined in IMN patients with the highest titer, but not a middle titer, when compared to those with the lowest titer. CONCLUSION: In contrast with previous meta-analyses, our results verified that PLA2R-ab can likely predict CR and spontaneous remission in IMN patients, instead of PR and relapse. Race, immunosuppressive agents, and duration of treatment may affect the prognostic value of PLA2R-ab. Considering that the remission rate of IMN patients with a middle level of PLA2R-ab was not different from that of patients with the lowest level, a proper cut-off value of PLA2R-ab for prognosis should be clarified.

Irisin Ameliorated Skeletal Muscle Atrophy by Inhibiting Fatty Acid Oxidation and Pyroptosis Induced by Palmitic Acid in Chronic Kidney Disease.

INTRODUCTION: Protein-energy waste (PEW) is a common complication in patients with chronic kidney disease (CKD), among which skeletal muscle atrophy is one of the most important clinical features of PEW. Pyroptosis is a type of proinflammatory, programmed cell death associated with skeletal muscle disease. Irisin, as a novel myokine, has attracted extensive attention for its protective role in the complications associated with CKD, but its role in muscle atrophy in CKD is unclear. METHODS: Palmitic acid (PA)-induced muscular atrophy was evaluated by a reduction in C2C12 myotube diameter. Muscle atrophy model was established in male C57BL/6J mice treated with 0.2% adenine for 4 weeks and then fed a 45% high-fat diet. Blood urea nitrogen and creatinine levels, body and muscle weight, and muscle histology were assessed. The expression of carnitine palmitoyltransferase 1A (CPT1A) and pyroptosis-related protein was analysed by Western blots or immunohistochemistry. The release of IL-1ß was detected by enzyme-linked immunosorbent assay. RESULTS: In this study, we showed that PA-induced muscular atrophy manifested as a reduction in C2C12 myotube diameter. During this process, PA can also induce pyroptosis, as shown by the upregulation of NLRP3, cleaved caspase-1 and GSDMD-N expression and the increased IL-1ß release and PI-positive cell rate. Inhibition of caspase-1 or NLRP3 attenuated PA-induced pyroptosis and myotube atrophy in C2C12 cells. Importantly, irisin treatment significantly ameliorated PA-induced skeletal muscle pyroptosis and atrophy. In terms of mechanism, PA upregulated CPT1A, a key enzyme of fatty acid oxidation (FAO), and irisin attenuated this effect, which was consistent with etomoxir (CPT1A inhibitor) treatment. Moreover, irisin improved skeletal muscle atrophy and pyroptosis in adenine-induced mice by regulating FAO. CONCLUSION: Our study firstly verifies that pyroptosis is a novel mechanism of skeletal muscle atrophy in CKD. Irisin ameliorates skeletal muscle atrophy by inhibiting FAO and pyroptosis in CKD, and irisin may be developed as a potential therapeutic agent for the treatment of muscle wasting in CKD patients.

Clinical Outcomes of Prolonged Antiplatelet Therapy after Percutaneous Coronary Intervention in Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) is not established in chronic kidney disease (CKD) patients. OBJECTIVE: In this meta-analysis, we evaluated the efficacy and safety of long duration DAPT compared with short duration DAPT in CKD patients after PCI. METHODS: We searched PubMed, Cochrane, and Embase to identify studies assessing the effect of DAPT duration in CKD patients with PCI. Endpoints included all-cause mortality, major adverse cardiovascular events (MACE), death or myocardial infarction (MI), revascularization, and bleeding. Event rates were compared with a random-effects model expressed by odds ratio (OR) and 95% confidence interval (CI). RESULTS: Six studies were included. CKD patients with extended DAPT duration were at a lower risk of mortality (OR 1.40, 95% CI: 1.11-1.77), MACE (OR 1.33, 95% CI: 1.17-1.51), mortality or MI (OR 1.24, 95% CI: 1.10-1.40), and stroke (OR 1.28, 95% CI: 1.05-1.56). However, there was no significant difference in revascularization and bleeding events between the two groups. Mortality was higher in patients with dialysis or drug-eluting stent comparing short- to long-term DAPT. CONCLUSIONS: Prolonged DAPT might decrease the risk of mortality, MACE, and stroke in patients with CKD without any significant difference in bleeding or revascularization. Additional studies are required to determine whether long-term DAPT could be considered for most CKD patients after PCI.

Risk factors for acute kidney injury in COVID-19 patients: an updated systematic review and meta-analysis.

Objectives: Acute kidney injury (AKI) is associated with increased mortality among coronavirus disease 2019 (COVID-19) patients. This meta-analysis aimed to identify risk factors for the development of AKI in patients with COVID-19.Methods: A systematic literature search was conducted in PubMed and EMBASE from 1 December 2019 to 1 January 2023. Due to significant study heterogeneity, meta-analyses were conducted using random-effects models. Meta-regression and sensitivity analysis were also performed.Results: A total of 153,600 COVID-19 patients from 39 studies were included, and 28,003 patients developed AKI. By meta-analysis, we discovered that age, male sex, obesity, black race, invasive ventilation, and the use of diuretics, steroids and vasopressors, in addition to comorbidities such as hypertension, congestive heart failure, chronic kidney disease, acute respiratory distress syndrome, and diabetes, were significant risk factors for COVID-19-associated AKI.Conclusions: Early detection of these risk factors is essential to reduce the incidence of AKI and improve the prognosis of COVID-19 patients.

Recovery of phosphorus from wastewater containing humic substances through vivianite crystallization: Interaction and mechanism analysis.

Vivianite crystallization has been regarded as a suitable option for recovering phosphorus (P) from P-containing wastewater. However, the presence of humic substances (HS) would inevitably affect the formation of vivianite crystals. Therefore, the influences of HS on vivianite crystallization and the changes in the harvested vivianite crystals were investigated in this study. The results suggested the inhibition effect of 70 mg/L HS on vivianite crystallization reached 12.24%, while it could be attenuated by increasing the pH and Fe/P ratio of the solution. Meanwhile, the addition of HS altered the size, purity, and morphology of recovered vivianite crystals due to the blockage of the growth sites on the crystal surface. Additionally, the formation of phosphate ester group, hydrogen bonding, and COOH-Fe2+ complexes are the potential mechanisms of HS interaction with vivianite crystals. The results obtained herein will help to elucidate the underlying mechanism of HS on vivianite crystallization from P-containing wastewater.