Development of insomnia in patients with stroke: A systematic review and meta-analysis.

BACKGROUND AND AIM: Stroke is a serious threat to human life and health, and post-stroke insomnia is one of the common complications severely impairing patients' quality of life and delaying recovery. Early understanding of the relationship between stroke and post-stroke insomnia can provide clinical evidence for preventing and treating post-stroke insomnia. This study was to investigate the prevalence of insomnia in patients with stroke. METHODS: The Web of Science, PubMed, Embase, and Cochrane Library databases were used to obtain the eligible studies until June 2023. The quality assessment was performed to extract valid data for meta-analysis. The prevalence rates were used a random-efect. I2 statistics were used to assess the heterogeneity of the studies. RESULTS: Twenty-six studies met the inclusion criteria for meta-analysis, with 1,193,659 participants, of which 497,124 were patients with stroke.The meta-analysis indicated that 150,181 patients with stroke developed insomnia during follow-up [46.98%, 95% confidence interval (CI): 36.91-57.18] and 1806 patients with ischemic stroke (IS) or transient ischemic attack (TIA) developed insomnia (47.21%, 95% CI: 34.26-60.36). Notably, 41.51% of patients with the prevalence of nonclassified stroke developed insomnia (95% CI: 28.86-54.75). The incidence of insomnia was significantly higher in patients with acute strokes than in patients with nonacute strokes (59.16% vs 44.07%, P < 0.0001).Similarly, the incidence of insomnia was significantly higher in the patients with stroke at a mean age of ≥65 than patients with stroke at a mean age of <65 years (47.18% vs 40.50%, P < 0.05). Fifteen studies reported the follow-up time. The incidence of insomnia was significantly higher in the follow-up for ≥3 years than follow-up for <3 years (58.06% vs 43.83%, P < 0.05). Twenty-one studies used the Insomnia Assessment Diagnostic Tool, and the rate of insomnia in patients with stroke was 49.31% (95% CI: 38.59-60.06). Five studies used self-reporting, that the rate of insomnia in patients with stroke was 37.58% (95% CI: 13.44-65.63). CONCLUSIONS: Stroke may be a predisposing factor for insomnia. Insomnia is more likely to occur in acute-phase stroke, and the prevalence of insomnia increases with patient age and follow-up time. Further, the rate of insomnia is higher in patients with stroke who use the Insomnia Assessment Diagnostic Tool.

The Glycine soja cytochrome P450 gene GsCYP82C4 confers alkaline tolerance by promoting reactive oxygen species scavenging.

Recent studies have demonstrated the crucial role of Cytochrome P450 enzymes (CYPs) in the production of secondary metabolites, phytohormones and antioxidants in plants. However, their functional characterization specifically under alkaline stress remains elusive. CYP82C4 was the key gene screened from a family of wild soybean CYPs in our previous studies. The aim of this present study was to clone the Glycine soja GsCYP82C4 gene and characterize its functions in Arabidopsis and Glycine max. The results showed that the GsCYP82C4 gene displayed a high expression in different plant tissues at mature stages compared to young stages. Further, higher temporal expression of the GsCYP82C4 gene was noted at 6, 12 and 24 h time points after alkali treatment in leaves compared to roots. In addition, overexpression of GsCYP82C4 improved alkaline stress tolerance in Arabidopsis via increased root lengths and fresh biomass and strengthened the antioxidant defense system via a reduction in superoxide radicals in transgenic lines compared to wild type (WT) and atcyp82c4 mutants. Further, the expression levels of stress-related marker genes were up-regulated in GsCYP82C4 OX lines under alkali stress. The functional analysis of GsCYP82C4 overexpression in soybean displayed better hairy root growth, increased fresh weight, higher antioxidant enzyme activities and reduced lipid peroxidation rates in OX lines compared to the soybean WT (K599) line. In total, our study displayed positive roles of GsCYP82C4 overexpression in both Arabidopsis and Glycine max to alleviate alkaline stress via altering expression abundance of stress responsive genes, stronger roots, higher antioxidant enzyme activities as well as reduced rates of lipid peroxidation and superoxide radicals.

Combination of an Autoantibody Panel and Alpha-Fetoprotein for Early Detection of Hepatitis B Virus-Associated Hepatocellular Carcinoma.

The purpose of this study was to identify biomarkers associated with hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) and to develop a new combination with good diagnostic performance. This study was divided into four phases: discovery, verification, validation, and modeling. A total of four candidate tumor-associated autoantibodies (TAAb; anti-ZIC2, anti-PCNA, anti-CDC37L1, and anti-DUSP6) were identified by human proteome microarray (52 samples) and bioinformatics analysis. Subsequently, these candidate TAAbs were further confirmed by indirect ELISA with two testing cohorts (120 samples for verification and 663 samples for validation). The AUC for these four TAAbs to identify patients with HBV-HCC from chronic hepatitis B (CHB) patients ranged from 0.693 to 0.739. Finally, a diagnostic panel with three TAAbs (anti-ZIC2, anti-CDC37L1, and anti-DUSP6) was developed. This panel showed superior diagnostic efficiency in identifying early HBV-HCC compared with alpha-fetoprotein (AFP), with an AUC of 0.834 [95% confidence interval (CI), 0.772-0.897] for this panel and 0.727 (95% CI, 0.642-0.812) for AFP (P = 0.0359). In addition, the AUC for this panel to identify AFP-negative patients with HBV-HCC was 0.796 (95% CI, 0.734-0.858), with a sensitivity of 52.4% and a specificity of 89.0%. Importantly, the panel in combination with AFP significantly increased the positive rate for early HBV-HCC to 84.1% (P = 0.005) and for late HBV-HCC to 96.3% (P < 0.001). Our findings suggest that AFP and the autoantibody panel may be independent but complementary serologic biomarkers for HBV-HCC detection. PREVENTION RELEVANCE: We developed a robust diagnostic panel for identifying patients with HBV-HCC from patients with CHB. This autoantibody panel provided superior diagnostic performance for HBV-HCC at an early stage and/or with negative AFP results. Our findings suggest that AFP and the autoantibody panel may be independent but complementary biomarkers for HBV-HCC detection.

Chiral phosphoric acid-catalyzed enantioselective [5+1] cycloaddition reaction of C,N-cyclic azomethine imines with isocyanides.

The first catalytic enantioselective [5+1] cycloaddition reactions of C,N-cyclic azomethine imines with isocyanides are reported herein. The method displays a broad substrate scope and atom-economy. A series of chiral tetrahydroisoquinoline containing indole skeletons were obtained in up to 90% yield with 95% ee under mild reaction conditions. A possible catalytic model was also proposed.

Excitation wavelength-dependent lanthanide-disalicylaldehyde coordination hybrid capable of distinguishing D2O from H2O.

The increasing demands in fields of anti-counterfeiting, fluorescence analysis, clinical therapy and LED illumination are urgently eager for more excellent optically switchable luminescent materials with the stable and multimodal fluorescence in single-component matrix. Herein, the lanthanide-disalicylaldehyde coordination hybrid H2Qj4/TbxEuy is proposed as an efficient luminescent matrix to connect terbium sensibilization with ESIPT (excited-state intramolecular proton transfer) effects, and three multi-emission hybrids are finally designed and synthesized by regulating Tb3+ and Eu3+ ratios. Surprisingly, the H2Qj4/Tb0.91Eu0.09 shows the excitation wavelength-dependent luminescence in solution which originates from two energy transfer ways of terbium sensibilization effect. It exhibits green and red lights under the 369 and 394 nm UV lamp, respectively. Three hybrids are further used as lab-on-a-molecule fluorescent probes to perform multianalyte detection for various solvents by selected fluorescent sensing channels. By means of PCA (principal component analysis) and HCA (hierarchical cluster analysis), all of them can successfully detect and discriminate17 common solvents, especially the H2O and D2O. Moreover, the H2Qj4/Tb0.91Eu0.09 also shows the wide linear responses of H2O content in D2O, discrimination of two-component solvent mixtures, hygroscopicity evaluation of D2O and information encryption which will advance the progress of multimodal luminescent materials and multianalyte chemosensors.

Ultrahigh Degree of Cationic Disorder, Configurational Entropy in New Type of High-Entropy Pseudobrookite Phase.

High-entropy ceramics exhibit various excellent properties owing to their high configurational entropy, which is caused by multi-principal elements sharing one lattice site. The configurational entropy will further increase significantly if multi-principal elements randomly share two different lattice sites. For this purpose, pseudobrookite phase containing two cationic lattice sites (A and B sites) is selected, and corresponding high-entropy pseudobrookite (M2+ 0.4 M3+ 1.2 )Ti1.4 O5 is synthesized. Herein, the distribution of the 2-valent and 3-valent cations in the A and B sites are analysed in depth. The distance between the A and B sites in the crystal structure models which are constructed by the Rietveld analysis is calculated and defined as distance d. Meanwhile, the atomic column positions in the STEM images are quantified by a model-based mathematical algorithm, and the corresponding distance d are calculated. By comparing the distance d, it is determine that the 2-valent and 3-valent cations are jointly and disorderly distributed in the A and B sites in high-entropy (M2+ 0.4 M3+ 1.2 )Ti1.4 O5 . The density functional theory (DFT) simulations also demonstrate that this type of crystal structure is more thermodynamically stable. The higher degree of cationic disorder leads to a higher configurational entropy in high-entropy (M2+ 0.4 M3+ 1.2 )Ti1.4 O5 , and endows high-entropy (M2+ 0.4 M3+ 1.2 )Ti1.4 O5 with very low thermal conductivity (1.187-1.249 W m-1  K-1 ).

Clinical impact of human parainfluenza virus infections before and during the COVID-19 pandemic in Southern China.

Human parainfluenza viruses (HPIVs) are a leading cause of acute respiratory tract infections (ARTIs). Non-pharmaceutical interventions (NPIs) were widely administered to combat the pandemic of the coronavirus disease 2019 (COVID-19). Respiratory specimens were obtained from 10,454 hospitalized children with ARTIs to detect HPIV. We investigated differences in epidemiological and clinical characteristics of HPIV infections before (2017-2019) and during the COVID-19 pandemic (2020-2022). HPIVs were detected in 392 (3.75%, 392/10,454) patients, of whom 70 (17.86%), 48 (12.24%), and 274 (69.90%) were positive for HPIV1, HPIV2, and HPIV3, respectively. Detection rates of HPIV3 were higher in 2020-2022 than in 2017-2019 (3.38% vs. 2.24%). The seasonal distribution of HPIV1 showed no difference, but HPIV3 peaked between September and December during the COVID-19 pandemic, which differed from previous epidemiological patterns. Compared to the period before the COVID-19 pandemic, there has been a noticeable decrease in the incidence of asthma, moist rales, and emesis in patients infected with HPIV1 and in asthma, expectoration, and severe pneumonia in patients infected with HPIV3 during 2020-2022. The detection rates of HPIV increased in Southern China during the COVID-19 outbreak, which underlines the importance of continuous surveillance of HPIV in the next epidemic season.

Oral proprietary Chinese medicine for lupus nephritis: A bayesian network meta-analysis.

Objective: To analyze the efficacy and safety of proprietary Chinese medicines for the treatment of Lupus Nephritis (LN) based on the reticulated meta analysis. The study aim to provide evidence-based evidence for the clinical treatment of LN. Methods: The studies related to the randomized controlled studies (RCTs) on the treatment of LN with oral proprietary Chinese medicines were obtained from China National Knowledge Infrastructure (CNKI), Database for Chinese Technical Periodicals (VIP), SinoMed, Wanfang, PubMed, Web of Science, Embase and Cochrane Library databases since its inception-August 2022. Cochrane tools were used for risk bias assessment, Stata 13.0 and ADDIS 1.16.5 software were used for net evidence analysis.Results.1) 41 RCTs with 3124 L N patients were included, involving 9 types of proprietary Chinese medicines.2) The meta-analysis showed that in terms of efficacy, the top 3 Chinese patent medicine interventions were Xin Gan Bao Capsule (XGB) +western medicines (WM), Huang Kui Capsule (HK) + WM, Kun Xian Capsule (KX) + WM; in terms of reducing adverse event rate, the top 3 Chinese patent medicine interventions were Yi Shen Hua Shi Granules (YSHS) + WM, Jin Shui Bao Capsule (JSB) + WM, HK + WM; in terms of reducing 24 h urine protein, the top 3 Chinese patent medicine interventions were XGB + WM, YSHS + WM, Bai Ling Capsule (BL) + WM; in terms of reducing blood creatinine (Cr), the top 3 Chinese patent medicine interventions were Yi Shen Granules (YS) + WM, JSB + WM, KX + WM; in terms of reducing urea nitrogen (BUN), the top 3 Chinese patent medicine interventions were Shen Kang Capsule (SK) + WM, HK + WM, JSB + WM; in terms of reducing systemic lupus erythematosus disease activity index (SLEDAI) scores, the top 3 Chinese patent medicine interventions were JSB + WM, BL + WM, YSHS + WM; in terms of improving complement C3, the top 3 Chinese patent medicine interventions were HK + WM, XGB + WM, BL + WM; in terms of improving complement C4, the top 3 Chinese patent medicine interventions were KX + WM, YSHS + WM, BL + WM. Conclusion: Xin Gan Bao Capsule has a good efficacy in improving efficiency and the level of complement C3, lowering 24 h urine protein. Jin Shui Bao Capsule and Huang Kui Capsule have a good efficacy in treating LN. However, more multicentre, large sample and high quality RCTs are needed for validation the results.

Development of ankylosing spondylitis in patients with ulcerative colitis: A systematic meta-analysis.

BACKGROUND: Ulcerative colitis (UC) is a manifestation of inflammatory bowel disease (IBD), which can cause inflammation of the intestinal tract. Ankylosing spondylitis (AS) is an inflammatory disease of the sacroiliac joints. Many studies have found that some UC patients progress to AS. In this study, we conducted a literature search and meta-analysis to investigate the prevalence of AS among UC patients during follow-up. METHODS: The studies related to the AS among patients with UC were obtained from PubMed, Web of Science, Embase, and Cochrane Library databases since its inception-December 2022. The literature was screened strictly according to inclusion and exclusion criteria. Forest plots were used to detect the overall incidence of AS in UC and to compare the risk ratios for the development of AS in the UC. The heterogeneity of studies was assessed using I2 statistical methods. RESULTS: 1) 17 studies with 98704 UC patients were included. 2)700 UC patients developed AS during follow-up (1.66%, 95% CI: 0.89-2.62%). Human leukocyte antigen B27 (HLA-B27) was reported in 3 studies. HLA-B27 positivity was significantly higher than the incidence of HLA-B27 negativity in AS patients (68.29% vs 31.71%, P < 0.0001). There was significantly increased risk of AS development in HLA-B27 positive IBD patients (RR: 22.17, 95% CI: 11.79-41.66, P < 0.0001). 3)The definite follow-up time was reported in 12 studies (range: 0.3-40 years). After follow-up for ≥5 years, the incidence of AS among patients with UC was 1.75% (95% CI: 0.62-3.37%). Meanwhile, after follow-up for <5 years, the incidence of AS among patients with UC was 1.41% (95% CI: 0.65-2.37%) which was significant. CONCLUSION: Patients with UC are more likely to develop AS in the future. Furthermore, the IBD patients are at a higher risk of AS who have positive HLA-B27. The incidence of AS increased with longer follow-up time.

Evidence summary on the non-pharmacological management of sleep disorders in shift workers.

PURPOSE: This study aimed to evaluate, and integrate the relevant evidence on the non-pharmacological management of sleep disorders in shift workers to provide a reference for improving sleep of shift workers. METHODS: According to the "6S" pyramid model of evidence, a comprehensive search was conducted in evidence-based databases, including BMJ-Best Practice, UpToDate, DynaMed, Cochrane Library, and Joanna Briggs Institute (JBI); clinical practice guideline websites, such as the Guidelines International Network; professional association websites, such as the World Sleep Society; and literature databases, including PubMed, Embase, CINAHL, China National Knowledge Infrastructure (CNKI), Wanfang Database, and Chinese Biology Medicine disc (CBM) from inception to November 30, 2022. Two researchers independently evaluated the literature in accordance with the evaluation standards; conducted the extraction, classification, and synthesis of the evidence; and evaluated its grade and recommendation grade. RESULTS: A total of 18 studies were included, including 2 clinical decisions, 2 guidelines, 3 expert consensuses, and 11 systematic reviews. In total, 25 pieces of evidence were summarized from 6 aspects: sleep assessment, sleep scheduling, sleep hygiene, light therapy, workplace intervention, and other managements. CONCLUSION: This study summarized the best evidence for the non-pharmacological management of sleep disorders in shift workers. Shift workers should reasonably arrange their sleep time and develop good sleep hygiene. Additionally, work organizations should jointly promote sleep to improve the sleep conditions of shift workers and promote their physical and mental health.

Discovery and Validation of Novel Genes in a Large Chinese Autism Spectrum Disorder Cohort.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that causes impairments in social communication and stereotypical behaviors, often accompanied by developmental delay or intellectual disability. A growing body of evidence suggests that ASD is highly heritable, and genetic studies have defined numerous risk genes. However, most studies have been conducted with individuals of European and Hispanic ancestry, and there is a lack of genetic analyses of ASD in the East Asian population. METHODS: We performed whole-exome sequencing on 772 Chinese ASD trios and combined the data with a previous study of 369 Chinese ASD trios, identifying de novo variants in 1141 ASD trios. We used single-cell RNA sequencing analysis to identify the cell types in which ASD-related genes were enriched. In addition, we validated the function of a candidate high-functioning autism gene in mouse models using genetic approaches. RESULTS: Our findings showed that ASD without developmental delay or intellectual disability carried fewer disruptive de novo variants than ASD with developmental delay or intellectual disability. Moreover, we identified 9 novel ASD candidate genes that were not present in the current ASD gene database. We further validated one such novel ASD candidate gene, SLC35G1, by showing that mice harboring a heterozygous deletion of Slc35g1 exhibited defects in interactive social behaviors. CONCLUSIONS: Our work nominates novel ASD candidate genes and emphasizes the importance of genome-wide genetic studies with ASD cohorts of different ancestries to reveal the comprehensive genetic architecture of ASD.

A method of motion estimation of segmental ventricular wall with tracking of ultrasonic echocardiogram.

BACKGROUND: Ultrasonic echocardiography is commonly used for monitoring myocardial dysfunction. However, it has limitations such as poor quality of echocardiography images and subjective judgment of doctors. METHODS: In this paper, a calculation model based on optical flow tracking of echocardiogram is proposed for the quantitative estimation motion of the segmental wall. To improve the accuracy of optical flow estimation, a method based on confidence-optimized multiresolution(COM) optical flow model is proposed to reduce the estimation errors caused by the large amplitude of myocardial motion and the presence of "shadows" and other image quality problems. In addition, motion vector decomposition and dynamic tracking of the ventricular region of interest are used to extract information regarding the myocardial segmental motion. The proposed method was validated using simulation images and 50 clinical cases (25 patients and 25 healthy volunteers) for myocardial motion analysis. RESULTS: The results demonstrated that the proposed method could track the motion information of myocardial segments well and reduce the estimation errors of optical flow caused due to the use of low-quality echocardiogram images. CONCLUSIONS: The proposed method improves the accuracy of motion estimation for the cardiac ventricular wall.

Increased RNA editing sites revealed as potential novel biomarkers for diagnosis in primary Sjögren's syndrome.

BACKGROUND: Transcriptome-wide aberrant RNA editing has been shown to contribute to autoimmune diseases, but its extent and significance in primary Sjögren's syndrome (pSS) are currently poorly understood. METHODS: We systematically characterized the global pattern and clinical relevance of RNA editing in pSS by performing large-scale RNA sequencing of minor salivary gland tissues obtained from 439 pSS patients and 130 non-pSS or healthy controls. FINDINGS: Compared with controls, pSS patients displayed increased global RNA-editing levels, which were significantly correlated and clinically relevant to various immune features in pSS. The elevated editing levels were likely explained by significantly increased expression of adenosine deaminase acting on RNA 1 (ADAR1) p150 in pSS, which was associated with disease features. In addition, genome-wide differential RNA editing (DRE) analysis between pSS and non-pSS showed that most (249/284) DRE sites were hyper-edited in pSS, especially the top 10 DRE sites dominated by hyper-edited sites and assigned to nine unique genes involved in the inflammatory response or immune system. Interestingly, among all DRE sites, six RNA editing sites were only detected in pSS and resided in three unique genes (NLRC5, IKZF3 and JAK3). Furthermore, these six specific DRE sites with significant clinical relevance in pSS showed a strong capacity to distinguish between pSS and non-pSS, reflecting powerful diagnostic efficacy and accuracy. CONCLUSION: These findings reveal the potential role of RNA editing in contributing to the risk of pSS and further highlight the important prognostic value and diagnostic potential of RNA editing in pSS.

Efficient recovery of bisphenol A from aqueous solution using K2CO3 activated carbon derived from starch-based polyurethane.

Endocrine-disrupting compounds (EDCs) are increasingly polluting water, making it of practical value to develop novel desirable adsorbents for removing these pollutants from wastewater. Here, a simple cross-linking strategy combined with gentle chemical activation was demonstrated to prepare starch polyurethane-activated carbon (STPU-AC) for adsorbing BPA in water. The adsorbents were characterized by various techniques such as FTIR, XPS, Raman, BET, SEM, and zeta potential, and their adsorption properties were investigated comprehensively. Results show that STPU-AC possesses a large surface area (1862.55 m2·g-1) and an abundance of functional groups, which exhibited superior adsorption capacity for BPA (543.4 mg·g-1) and favorable regenerative abilities. The adsorption of BPA by STPU-AC follows a pseudo-second-order kinetic model and a Freundlich isotherm model. The effect of aqueous solution chemistry (pH and ionic strength) and the presence of other contaminants (phenol, heavy metals, and dyes) on BPA adsorption was also analyzed. Moreover, theoretical studies further demonstrate that hydroxyl oxygen and pyrrole nitrogen are the primary adsorption sites. We found that the efficient recovery of BPA was associated with pore filling, hydrogen-bonding interaction, hydrophobic effects, and π-π stacking. These findings demonstrate the promising practical application of STPU-AC and provide a basis for the rational design of starch-derived porous carbon.

Focusing on testosterone levels in male: A half-longitudinal study of polycyclic aromatic hydrocarbon exposure and diastolic blood pressure in coke oven workers.

Polycyclic aromatic hydrocarbons (PAHs) can interfere with testosterone levels, and low levels of testosterone are associated with increased cardiovascular events. To explore the role of testosterone in PAHs exposure and cardiovascular health, we used data from the 2011-2016 National Health and Nutrition Examination Survey (NHANES) and a longitudinal database of 332 male coke oven workers from China. The urine PAHs, tobacco metabolites and plasma testosterone levels of coke oven workers were measured. There were inverse associations between serum (plasma) testosterone concentrations and the risk of dysarteriotony and dyslipidemia among the NHANES participants and coke oven workers. The results of the cross-lagged panel analysis among workers showed that the decrease in testosterone preceded the increase in diastolic blood pressure (DBP), and the absolute value of the path coefficient from baseline testosterone to follow-up DBP (ß2 = -8.162, P = 0.077) was significantly larger than the absolute value of the path coefficient from baseline DBP to follow-up testosterone (ß1 = -0.001, P = 0.781). Results from the half-longitudinal mediation analysis showed that baseline hydroxyfluorene predicted significant decreases in plasma testosterone from baseline to follow-up (path a: 0.71, 95% CI: 1.26, -0.16), whereas plasma testosterone at baseline also predicted significant increments in DBP from baseline to follow-up (path b: 9.22, 95% CI: 17.24, -1.19). The indirect effect of PAHs on DBP via plasma testosterone level was marginally significant (test for indirect effects a*b (P = 0.08)). In conclusion, testosterone level is a longitudinal precursor to increased DBP and plays an essential role in the association between PAHs exposure and damage to the cardiovascular system. Coke oven workers with low plasma testosterone levels are more likely to experience adverse changes in blood pressure and lipid levels after exposure to PAHs.

Experimental investigation of the creep damage evolution of coal rock around gas extraction boreholes at different water contents.

The creep process of the coal rock around the extraction boreholes under stress-water coupling is an important factor affecting the stability of the boreholes. To study the influence of the water content of perimeter of the coal rock around the boreholes on its creep damage, a creep intrinsic model considering water damage was established by introducing the plastic element model from the Nishihara model. To study the steady-state strain and damage evolution of coal rocks containing pores, and verify the practicality of the model, a graded loading water-bearing creep test was designed to explore the role of different water-bearing conditions in the creep process. The following conclusions were obtained: 1) water has a physical erosion and softening water wedge effect on the perimeter of the coal rock around the boreholes, which affects the loading axial strain and displacement of the perforated specimens; 2) an increase in water content reduces the time taken for perforated specimens to enter the creep phase, making the accelerated creep phase come earlier; 3) the parameters of the water damage model are considered to be exponentially related with the water content. The experimental data are similar to the results of the model parameters, and the model shows some practicality; 4) the damage variables in the accelerated creep phase increase rapidly throughout the creep process, leading to local instability in the borehole. The findings of the study provide important theoretical implications for the study of instability in gas extraction boreholes.

CASMART, a one-step CRISPR Cas12a-mediated isothermal amplification for rapid and high-resolution digital detection of rare mutant alleles.

Convenient, ultrasensitive, and accurate detection of rare variants is essential for early cancer diagnosis and precision medicine, however, despite years of efforts, tools that have all these qualities remain elusive. Here, we developed a one-step CRISPR/Cas12a-based digital diagnostic platform for accurately quantifying mutant alleles, referred to as the CRISPR ASsoaciated Mutation Allele Rapid Test (CASMART). The platform accurately quantifies the variant allele frequency of EGFR L858R within 1 h at 42 °C and can detect mutant targets as low as 0.3 copies/µL (0.498 aM) in mock multiplex cfDNA samples. We further investigated the applicability of CASMART using human genomic samples with confirmed EGFR L858R mutations previously measured variant allele frequency by next-generation sequencing. Comparison across platforms revealed equivalent detection performance (Pearson's correlation coefficient, R2 = 0.9208) and high quantification accuracy for mutation allele frequency (intraclass correlation coefficient = 0.959). Our one-step approach enables easy and accurate variant allele frequency measurement of rare mutant alleles without PCR instrumentation, while the assay time was reduced by approximately half compared to the digital PCR with the shortest turnaround. The CASMART is an alternative to conventional single nucleotide polymorphism detection methods with great potential as a next-generation biosensor for rapidly quantifying the variant allele fraction, especially in resource-limited settings.

Microbiota dysbiosis in primary Sjögren's syndrome and the ameliorative effect of hydroxychloroquine.

The human microbiome plays an important role in autoimmune diseases. However, there is limited knowledge regarding the microbiota in individuals with primary Sjögren's syndrome (pSS). Here, we perform 16S ribosomal RNA gene sequencing of fecal, oral, and vaginal samples from a cohort of 133 individuals with pSS, 56 with non-pSS, and 40 healthy control (HC) individuals. Dysbiosis in the gut, oral, and vaginal microbiome is evident in patients with pSS, and oral samples demonstrate the greatest extent of microbial variation. Multiple key indicator bacteria and clinical characteristics are identified across different body sites, implying that microbial dysbiosis has important roles in the pathogenesis of pSS. Furthermore, we observe pSS-like dysbiosis in individuals with pre-clinical pSS or non-pSS-related disease, revealing that microbial shifts could appear prior to pSS. After hydroxychloroquine (HCQ) treatment, microbial dysbiosis in individuals with pSS is partially resolved, although the microbiota composition remain disordered. These results contribute to the overall understanding of the relationship between the microbiome and pSS.