Implementation of Newborn Screening for Mucopolysaccharidosis Type IVA and Long-Term Monitoring in Taiwan.

BACKGROUND: Mucopolysaccharidosis IVA (MPS IVA) is a rare lysosomal storage disorder arising from a deficiency in N-acetylgalactosamine-6-sulfatase (GALNS). METHODS: From September 2019 to October 2023, a total of 264,843 Taiwanese newborns underwent screening for MPS IVA using dried blood spots and tandem mass spectrometry. RESULTS: Among the 95 referred infants, nine (9%) were confirmed to have MPS IVA (Group 1), 18 (19%) were highly suspected to have MPS IVA (Group 2), 61 (64%) were identified as heterozygotes of MPS IVA (Group 3), and seven (7%) were determined not to have MPS IVA (Group 4). A total of 34 different GALNS (HGNC:4122) gene variants were identified through our MPS IVA newborn screening program. The most prevalent variant was c.857C>T p.(Thr286Met), found in 33 cases (29%), followed by c.953T>G p.(Met318Arg) in 22 cases (19%). Intravenous enzyme replacement therapy (ERT) was initiated in five patients at ages ranging from 0.3 to 1.7 years. The estimated incidence of MPS IVA in this screening program was 3.4 per 100,000 live births. CONCLUSIONS: Due to the progressive nature of MPS IVA, an early diagnosis facilitated by newborn screening and prompt initiation of ERT before irreversible organ damage occurs may result in improved clinical outcomes.

Autophagy accompanying the developmental process of male germline stem cells.

Germline stem cells are a crucial type of stem cell that can stably pass on genetic information to the next generation, providing the necessary foundation for the reproduction and survival of organisms. Male mammalian germline stem cells are unique cell types that include primordial germ cells and spermatogonial stem cells. They can differentiate into germ cells, such as sperm and eggs, thereby facilitating offspring reproduction. In addition, they continuously generate stem cells through self-renewal mechanisms to support the normal function of the reproductive system. Autophagy involves the use of lysosomes to degrade proteins and organelles that are regulated by relevant genes. This process plays an important role in maintaining the homeostasis of germline stem cells and the synthesis, degradation, and recycling of germline stem cell products. Recently, the developmental regulatory mechanism of germline stem cells has been further elucidated, and autophagy has been shown to be involved in the regulation of self-renewal and differentiation of germline stem cells. In this review, we introduce autophagy accompanying the development of germline stem cells, focusing on the autophagy process accompanying the development of male spermatogonial stem cells and the roles of related genes and proteins. We also briefly outline the effects of autophagy dysfunction on germline stem cells and reproduction.

Modeling nitrogen removal performance based on novel microbial activity indicators in WWTP by machine learning and biological interpretation.

Modeling the pollutant removal performance of wastewater treatment plants (WWTPs) plays a crucial role in regulating their operation, mitigating effluent anomalies and reducing operating costs. Pollutants removal in WWTPs is closely related to microbial activity. However, there is extremely limited knowledge on the models accurately characterizing pollutants removal performance by microbial activity indicators. This study proposed a novel specific oxygen uptake rate (SOURATP) with adenosine triphosphate (ATP) as biomass. Firstly, it was found that SOURATP and total nitrogen (TN) removal rate showed similar fluctuated trends, and their correlation was stronger than that of TN removal rate and common SOURMLSS with mixed liquor suspended solids (MLSS) as biomass. Then, support vector regressor (SVR), K-nearest neighbor regressor (KNR), linear regressor (LR), and random forest (RF) models were developed to predict TN removal rate only with microbial activity as features. Models utilizing the novel SOURATP resulted in better performance than those based on SOURMLSS. A model fusion (MF) algorithm based on the above four models was proposed to enhance the accuracy with lower root mean square error (RMSE) of 2.25 mg/L/h and explained 75% of the variation in the test data with SOURATP as features as opposed to other base learners. Furthermore, the interpretation of predictive results was explored through microbial community structure and metabolic pathway. Strong correlations were found between SOURATP and the proportion of nitrifiers in aerobic pool, as well as between heterotrophic bacteria respiratory activity (SOURATP_HB) and the proportion of denitrifies in anoxic pool. SOURATP also displayed consistent positive responses with most key enzymes in Embden-Meyerhof-Parnas pathway (EMP), tricarboxylic acid cycle (TCA) and oxidative phosphorylation cycle. In this study, SOURATP provides a reliable indication of the composition and metabolic activity of nitrogen removal bacteria, revealing the potential reasons underlying the accurate predictive result of nitrogen removal rates based on novel microbial activity indicators. This study offers new insights for the prediction and further optimization operation of WWTPs from the perspective of microbial activity regulation.

[Screening for Characteristic Genes of Different Traditional Chinese Medicine Syndromes of Psoriasis Vulgaris: A Study Based on Bioinformatics and Machine Learning]. / ç”Ÿç‰©ä¿¡æ¯å­¦å’Œæœºå™¨å­¦ä¹ ç­›é€‰é“¶å±‘ç— ä¸­åŒ»è¯åž‹ç‰¹å¾åŸºå› .

Objective: To screen for the key characteristic genes of the psoriasis vulgaris (PV) patients with different Traditional Chinese Medicine (TCM) syndromes, including blood-heat syndrome (BHS), blood stasis syndrome (BSS), and blood-dryness syndrome (BDS), through bioinformatics and machine learning and to provide a scientific basis for the clinical diagnosis and treatment of PV of different TCM syndrome types. Methods: The GSE192867 dataset was downloaded from Gene Expression Omnibus (GEO). The limma package was used to screen for the differentially expressed genes (DEGs) of PV, BHS, BSS, and BDS in PV patients and healthy populations. In addition, KEGG (Kyoto Encyclopedia of Genes and Genes) pathway enrichment analysis was performed. The DEGs associated with PV, BHS, BSS, and BDS were identified in the screening and were intersected separately to obtain differentially characterized genes. Out of two algorithms, the support vector machine (SVM) and random forest (RF), the one that produced the optimal performance was used to analyze the characteristic genes and the top 5 genes were identified as the key characteristic genes. The receiver operating characteristic (ROC) curves of the key characteristic genes were plotted by using the pROC package, the area under curve (AUC) was calculated, and the diagnostic performance was evaluated, accordingly. Results: The numbers of DEGs associated with PV, BHS, BSS, and BDS were 7699, 7291, 7654, and 6578, respectively. KEGG enrichment analysis was focused on Janus kinase (JAK)/signal transducer and activator of transcription (STAT), cyclic adenosine monophosphate (cAMP), mitogen-activated protein kinase (MAPK), apoptosis, and other pathways. A total of 13 key characteristic genes were identified in the screening by machine learning. Among the 13 key characteristic genes, malectin (MLEC), TUB like protein 3 (TULP3), SET domain containing 9 (SETD9), nuclear envelope integral membrane protein 2 (NEMP2), and BTG anti-proliferation factor 3 (BTG3) were the key characteristic genes of BHS; phosphatase 15 (DUSP15), C1q and tumor necrosis factor related protein 7 (C1QTNF7), solute carrier family 12 member 5 (SLC12A5), tripartite motif containing 63 (TRIM63), and ubiquitin associated protein 1 like (UBAP1L) were the key characteristic genes of BSS; recombinant mouse protein (RRNAD1), GTPase-activating protein ASAP3 Protein (ASAP3), and human myomesin 2 (MYOM2) were the key characteristic genes of BDS. Moreover, all of them showed high diagnostic efficacy. Conclusion: There are significant differences in the characteristic genes of different PV syndromes and they may be potential biomarkers for diagnosing TCM syndromes of PV.

[Effects of 4-hydroxy-2(3H)-benzoxazolone on proliferation and apoptosis of pancreatic cancer L3.6 cells].

This study explored the effects of 4-hydroxy-2(3H)-benzoxazolone(HBOA) on the proliferation and apoptosis of pancreatic cancer cells and its molecular mechanism. The L3.6 cells cultured in vitro were treated with HBOA of 0-1.0 mmol·L~(-1). The cell viability was detected by the cell counting kit-8(CCK-8) method, and the half inhibitory concentration(IC_(50)) was analyzed to determine the drug concentration and time. The cell morphology was observed under an inverted microscope and by acridine orange(AO) staining. The ability of proliferation and self-renewal were evaluated through live cell counting and colony formation experiments. The cell cycle progression and cell apoptosis rate were detected by flow cytometry. The morphology of cell apoptosis was observed by scanning electron microscopy. The mRNA expression of proliferating cell nuclear antigen(PCNA), cyclinA1, cyclinA2, cyclin dependent kinase 2(CDK2), and cyclin dependent kinase inhibitor 1A(P21) were determined by qPCR. The level of reactive oxygen species(ROS), lipid peroxide, and mitochondrial membrane potential were measured by flow cytometry. The activity of protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathway was detected by Western blot. Compared with the control group, the cells treated with HBOA exhibited a significant decrease in viability. Then the optimal concentration and intervention time of HBOA were determined to be 0.4 mmol·L~(-1), 0.6 mmol·L~(-1), and 48 h. Compared with the control group, groups with HBOA of 0.4 mmol·L~(-1 )and 0.6 mmol·L~(-1) showed a significant suppression in cell proliferation and colony formation ability, down-regulated mRNA of PCNA, cyclinA1, cyclinA2, and CDK2, up-regulated P21 mRNA, S-phase cell cycle arrest, and increased cell apoptosis rate. There was an appearance of apoptotic bodies, increased ROS and lipid peroxide, decreased mitochondrial membrane potential(with a significant decrease in 0.6 mmol·L~(-1) group), and down-regulated p-Akt and p-mTOR proteins. The results show that HBOA inhibits the proliferation of pancreatic cancer L3.6 cells and induces cell apoptosis, which may be related to the increase in reactive oxygen species and the inhibition of the Akt/mTOR pathway.

Nanomaterials-Enabled Physicochemical Antibacterial Therapeutics: Toward the Antibiotic-Free Disinfections.

Bacterial infection continues to be an increasing global health problem with the most widely accepted treatment paradigms restricted to antibiotics. However, the overuse and misuse of antibiotics have triggered multidrug resistance of bacteria, frustrating therapeutic outcomes, and leading to higher mortality rates. Even worse, the tendency of bacteria to form biofilms on living and nonliving surfaces further increases the difficulty in confronting bacteria because the extracellular matrix can act as a robust barrier to prevent the penetration of antibiotics and resist environmental damage. As a result, the inability to eliminate bacteria and biofilms often leads to persistent infection, implant failure, and device damage. Therefore, it is of paramount importance to develop alternative antimicrobial agents while avoiding the generation of bacterial resistance to prevent the large-scale growth of bacterial resistance. In recent years, nano-antibacterial materials have played a vital role in the antibacterial field because of their excellent physical and chemical properties. This review focuses on new physicochemical antibacterial strategies and versatile antibacterial nanomaterials, especially the mechanism and types of 2D antibacterial nanomaterials. In addition, this advanced review provides guidance on the development direction of antibiotic-free disinfections in the antibacterial field in the future.

Serum interα-trypsin inhibitor heavy chain H4 may be an anti-inflammatory marker reflecting disease risk, activity and treatment outcome of ankylosing spondylitis.

Interα-trypsin inhibitor heavy chain H4 (ITIH4) modulates inflammation and immunity, which take part in the pathogenesis of ankylosing spondylitis (AS). The current research intended to discover the clinical value of serum ITIH4 quantification for AS management. Serum ITIH4 among 80 AS patients before current treatment initiation (baseline) at weeks (W) 4, 8 and 12 after treatment was detected by ELISA. Serum ITIH4 from 20 disease controls (DCs) and 20 healthy controls (HCs) was detected. ITIH4 expression was lower in AS patients than in DCs (p = 0.002) and HCs (p < 0.001). Among AS patients, ITIH4 was negatively associated with C-reactive protein (CRP) (r = -0.311, p = 0.005), bath AS disease activity index (BASDAI) (r = -0.223, p = 0.047), total pack pain (r = -0.273, p = 0.014) and AS disease activity score (ASDAS) (CRP) (r = -0.265, p = 0.018). Meanwhile, ITIH4 was negatively related to tumor necrosis factor (TNF)-α (r = -0.364, p = 0.001), interleukin (IL)-1ß (r = -0.251, p = 0.025), IL-6 (r = -0.292, p = 0.009) and IL-17A (r = -0.254, p = 0.023). After treatment, the assessment of the spondylitis arthritis international society 40 response rate was 28.7% at W4, 46.3% at W8 and 55.0% at W12; ITIH4 showed an increasing trend from baseline to W12 (p < 0.001). Furthermore, ITIH4 at W8 (p = 0.020) and W12 (p = 0.035), but not at baseline or W4 (both p > 0.05), was enhanced in response patients vs. nonresponse patients. Additionally, ITIH4 at W12 was increased in AS patients receiving TNF inhibitors vs. those receiving nonsteroidal anti-inflammatory drugs (NSAIDs) (p = 0.024). Serum ITIH4 increases after treatment, and its augmentation is correlated with lower disease activity, decreased inflammation and enhanced treatment response in AS patients.

Effects of qufeng xuanfei formula in guinea pig model of airway hyperergy.

This work aimed to clarify the potential regulating effects of Qufeng Xuanfei formula (QFXF) on airway neurogenic inflammation and its underlying target signal pathway. Guinea pig model of airway hyperergy (AHR) was used. The relative susceptibility of major proteins to airway neurogenic inflammation was assessed using Western blot immunoassay followed by being separated by SDS-PAGE. Compared to the model group, QFXF of all concentrations effectively depressed the capsaicin enhanced cough in guinea pigs and the peak values of airway resistance significantly decreased. The results illustrated that QFXF alleviated cough symptom in guinea pigs and reduced airway neurogenic inflammation when compared to AHR model group. Airway inflammation and damage, as well as the levels of NGF, SP and c-Fos in QFXF decreased the most in the high-dose group. The mechanism of antitussive activity may be associated with reducing airway inflammation. QFXF displayed effect on chronic cough through reducing the levels of neuropeptides, attenuating airway inflammation and promoting recovery from disease to decrease the airway neuro sensitivity, suggesting that the potential mechanism may be related to Ras/ERK/c-Fos pathway.

Tunable Structured MXenes With Modulated Atomic Environments: A Powerful New Platform for Electrocatalytic Energy Conversion.

Owing to their rich surface chemistry, high conductivity, tunable bandgap, and thermal stability, structured 2D transition-metal carbides, nitrides, and carbonitrides (MXenes) with modulated atomic environments have emerged as efficient electrochemical energy conversion systems in the past decade. Herein, the most recent advances in the engineering of tunable structured MXenes as a powerful new platform for electrocatalytic energy conversion are comprehensively summarized. First, the state-of-the-art synthetic and processing methods, tunable nanostructures, electronic properties, and modulation principles of engineering MXene-derived nanoarchitectures are focused on. The current breakthroughs in the design of catalytic centers, atomic environments, and the corresponding structure-performance correlations, including termination engineering, heteroatom doping, defect engineering, heterojunctions, and alloying, are discussed. Furthermore, representative electrocatalytic applications of structured MXenes in energy conversion systems are also summarized. Finally, the challenges in and prospects for constructing MXene-based electrocatalytic materials are also discussed. This review provides a leading-edge understanding of the engineering of various MXene-based electrocatalysts and offers theoretical and experimental guidance for prospective studies, thereby promoting the practical applications of tunable structured MXenes in electrocatalytic energy conversion systems.

Overexpression of hsa_circ_0022742 suppressed hyperglycemia-induced endothelial dysfunction by targeting the miR-503-5p/FBXW7 axis.

Type I and II diabetes adversely affect the microvasculature of several organs, although the regulatory mechanisms remain unclear. Previous studies have found that differentially expressed circRNAs associated with hyperglycemia (HG) induce endothelial dysfunction. In the present study, high-throughput sequencing was employed to assess abnormal circRNA expression in human umbilical vein endothelial cells (HUVECs) after HG treatment. Then, bioinformatics analysis, luciferase reporting analysis, angiogenic differentiation analysis, flow cytometry, and qRT-PCR analysis were performed to investigate the underlying regulatory mechanism and targets. The results demonstrate that hsa_circ_0022742 expression in HUVECs was decreased by HG treatment and overexpression of hsa_circ_0022742 suppressed HG-induced endothelial dysfunction. Luciferase analysis showed that miR-503-5p and FBXW7 were downstream targets of hsa_circ_0022742. Both overexpression of FBXW7 and inhibition of miR-503-5p reversed the protective effect of hsa_circ_0022742 against HG-induced endothelial dysfunction, including apoptosis, abnormal vascular differentiation, and secretion of inflammatory factors, indicating that hsa_circ_0022742 enhanced FBXW7 expression by sponging miR-503-5p. Taken together, these findings demonstrate that overexpression of hsa_circ_0022742 suppressed HG-induced endothelial dysfunction by targeting the miR-503-5p/FBXW7 axis.

π-Conjugated Copper Phthalocyanine Nanoparticles as Highly Sensitive Sensor for Colorimetric Detection of Biomarkers.

Though numerous nanomaterials with enzyme-like activities have been utilized as probes and sensors for detecting biological molecules, it is still challenging to construct highly sensitive detectors for biomarkers using polymeric materials. Benefiting from the π-d delocalization effect of electrons, excellent metal-chelating property, high electron transferability, and good chemical stability of π-conjugated phthalocyanine, the design of the copper phthalocyanine-based conjugated polymer nanoparticles (Cu-PcCP NPs) as a colorimetric sensor for a variety of biomarkers is reported. The Cu-PcCP NPs are synthesized through a simple microwave-assisted polymerization, and their chemical structures are thoroughly characterized. The colorimetric results of Cu-PcCP NPs demonstrate excellent peroxidase-like detecting activity and also great substrate selectivity than most of the reported Cu-based nanomaterials. The Cu-PcCP NPs can achieve a detection limit of 4.88 µM for the H2 O2 , 4.27 µM for the L-cysteine, and 21.10 µM for the glucose via a cascade catalytic system, which shows comparable detecting sensitivity as that of many earlier reported enzyme-like nanomaterials. Moreover, Cu-PcCP NPs present remarkable resistance to harsh conditions, including high temperature, low pH, and excessive salts. These highly specific π-conjugated copper-phthalocyanine nanoparticles not only overcome the current limitation of polymeric material-based sensors but also provide a new direction for designing next-generation enzyme-like nanomaterial-based colorimetric biosensors.

Novel Deep Eutectic Solvent-Hydrogel Systems for Synergistic Transdermal Delivery of Chinese Herb Medicine and Local Treatments for Rheumatoid Arthritis.

In this study, a novel hydrogel system incorporating an amino acid-based deep eutectic solvent (DES) was prepared, and the skin-permeation enhancement of traditional Chinese herb medicine was evaluated using "sanwujiaowan" extract as the model formula. Briefly, a DES-extract complex was constructed by co-heating the herb formula extracts with the amino acid as the hydrogen receptor and citric acid as the hydrogen donor. The DES-extract complex demonstrated excellent dissolution and skin permeability of the complicated ingredients in the extracts. Consequently, the DES-extract complex was introduced to a hydrogel system, which showed better mechanical properties and viscoelasticity performance. Using a collagen-induced arthritis rat model, the DES-hydrogels exerted an enhanced therapeutic effect that significantly reduced the inflammatory response with systemic toxicity of the extracts. Therefore, our work suggests a novel strategy for synergistic transdermal delivery of Chinese herb medicine and local treatments for rheumatoid arthritis.

Associations between UASMS2 polymorphism in leptin gene and growth, carcass and meat quality traits of cattle: a meta-analysis.

Although numerous studies investigated the effect of UASMS2 polymorphism in leptin gene on cattle production, a consensus has not yet been reached. Therefore, we reviewed and meta-analyzed the effects of UASMS2 on cattle. We searched potentially relevant studies from seven databases (to December 25, 2019). Standard mean difference along with 95% confidence intervals was calculated to assess the strength of association through the random-effects model. Six published articles containing 1378 cattle samples were included in our meta-analysis. We found UASMS2 was not related to carcass weight, dressing percentage and loin muscle area in the recessive genetic model, but there was a significant association between UASMS2 and average daily weight gain, dry matter intake, body weight, marbling score, and backfat thickness. This meta-analysis indicated that UASMS2 was associated with growth and meat quality traits of cattle, implying that this SNP can be used reliably in beef cattle breeding. This study may provide valuable information on improving beef yield and quality in cattle production.

Gestational PM2.5 exposure may increase the risk of small for gestational age through maternal blood pressure and hemoglobin: A mediation analysis based on a prospective cohort in China, 2014-2018.

BACKGROUND: Maternal gestational PM2.5 exposure was associated with small for gestational age (SGA). Identifying potential mediating factors may help design preventive strategies to reduce this risk. OBJECTIVE: This study aimed to explore the roles of maternal blood pressure and hemoglobin may play in the PM2.5 exposure and SGA relationship among 117,162 births in 16 counties across China during 2014-2018. METHODS: Daily PM2.5 concentration was collected from China National Environmental Monitoring Center. According to maternal residency during pregnancy, the PM2.5 exposure for each trimester and the whole pregnancy was assessed using an inverse-distance weighting approach. Repeated measurements of maternal blood pressure and hemoglobin during pregnancy were collected for each woman. We estimated the total effect of gestational PM2.5 exposure on SGA, and further tested the mediation effects of maternal blood pressure and hemoglobin concentration during pregnancy. RESULTS: Of 117,162 included mother-infant pairs, 11,361 (9.7 %) were SGA. The odds ratios of SGA associated with PM2.5 exposure (per 10 µg/m3 increase) in the second trimester and the whole pregnancy were 1.023 (95 % CI: 1.009, 1.037) and 1.024 (1.001, 1.048), respectively. We identified the independent mediating effect of blood pressure and hemoglobin in the second and third trimesters, with the proportion of mediation ranging from 1.64 % to 5.78 % and 2.40 % to 8.70 %, respectively. When considering the mediators jointly, we found a stronger mediating effect with a proportion of mediation ranging from 3.93 % to 13.69 %. DISCUSSION: Increases in maternal blood pressure and hemoglobin in the second and third trimesters can independently and jointly mediate the effects of gestational PM2.5 exposure on SGA. Monitoring and managing maternal blood pressure and hemoglobin during prenatal care may constitute a promising avenue to reducing SGA risk associated with gestational PM2.5 exposure.

Effect of BMP-Wnt-Nodal signal on stem cell differentiation.

The generation of germ cells from embryonic stem cells in vitro has current historical significance. Western blot, qPCR, immunofluorescence and flow cytometry assays were used to investigate the differences in expression levels of totipotency and specific markers for Wnt regulation and the related signalling pathways during primordial germ cell-like cell (PGCLC) induction and differentiation. During PGCLC induction, activation of WNT3a increased the expression of NANOG, SOX2 and OCT4, but Mvh, DAZL, Blimp1, TFAP2C, Gata4, SOX17, EOMES, Brachyury and PRDM1 expression levels were significantly reduced. Inhibition of the WNT signal demonstrated the opposite effect. Similarly, inhibitors of BMP and the Nodal/Activin signal were used to determine the effect of signal pathways on differentiation. CER1 affected the Wnt signal and differentiation, but the inhibitor SB only regulated differentiation. BMP-WNT-NODAL were mainly responsible for regulating differentiation. Our results provide a reliable theoretical basis and feasibility for further clinical medical research.

Association of PM2.5 and PM10 with Acute Exacerbation of Chronic Obstructive Pulmonary Disease at lag0 to lag7: A Systematic Review and Meta-Analysis.

This study aimed to conduct a meta-analysis to investigate whether short-term exposure to fine (PM2.5) and coarse (PM10) particulate matter was associated with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) hospitalization, emergency room visit, and outpatient visit at different lag values. PubMed, Embase, and the Cochrane Library were searched for relevant papers published up to March 2021. For studies reporting results per 1-µg/m3 increase in PM2.5, the results were recalculated as per 10-µg/m3 increase. We manually calculated the RRs for these two studies and transferred the RRs to estimate 10 µg/m3 increases in PM2.5. Automation tools were initially used to remove ineligible studies. Two reviewers independently screened the remaining records and retrieved reports. Twenty-six studies (28 datasets; 7,018,419 patients) were included. There was a significant association between PM2.5 and AECOPD events on lag0 (ES = 1.01, 95%CI: 1.01-1.02, p < 0.001; I2=88.6%, Pheterogeneity<0.001), lag1 (ES = 1.00, 95%CI: 1.00-1.01, p < 0.001; I2=82.5%, Pheterogeneity<0.001), lag2 (ES = 1.01, 95%CI: 1.01-1.01, p < 0.001; I2=90.6%, Pheterogeneity<0.001), lag3 (ES = 1.01, 95%CI: 1.00-1.01, p < 0.001; I2=88.9%, Pheterogeneity<0.001), lag4 (ES = 1.00, 95%CI: 1.00-1.01, p < 0.001; I2=83.7%, Pheterogeneity<0.001), and lag7 (ES = 1.00, 95%CI: 1.00-1.00, p < 0.001; I2=0.0%, Pheterogeneity=0.743). The subgroup analyses showed that PM2.5 influenced the rates of hospitalization, emergency room visits, and outpatient visits. Similar trends were observed with PM10. The risk of AECOPD events (hospitalization, emergency room visit, and outpatient visit) was significantly increased with a 10-µg/m3 increment in PM2.5 and PM10 from lag0 to lag7.List Of Abbreviations: particulate matter (PM2.5 and PM10); acute exacerbation of chronic obstructive pulmonary disease (AECOPD); Chronic obstructive pulmonary disease (COPD); Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA); Effect sizes [48]; confidence intervals (CIs).

Effect of Remote Ischemic Conditioning vs Usual Care on Neurologic Function in Patients With Acute Moderate Ischemic Stroke: The RICAMIS Randomized Clinical Trial.

Importance: Preclinical and clinical studies have suggested a neuroprotective effect of remote ischemic conditioning (RIC), which involves repeated occlusion/release cycles on bilateral upper limb arteries; however, robust evidence in patients with ischemic stroke is lacking. Objective: To assess the efficacy of RIC for acute moderate ischemic stroke. Design, Setting, and Participants: This multicenter, open-label, blinded-end point, randomized clinical trial including 1893 patients with acute moderate ischemic stroke was conducted at 55 hospitals in China from December 26, 2018, through January 19, 2021, and the date of final follow-up was April 19, 2021. Interventions: Eligible patients were randomly assigned within 48 hours after symptom onset to receive treatment with RIC (using a pneumatic electronic device and consisting of 5 cycles of cuff inflation for 5 minutes and deflation for 5 minutes to the bilateral upper limbs to 200 mm Hg) for 10 to 14 days as an adjunct to guideline-based treatment (n = 922) or guideline-based treatment alone (n = 971). Main Outcomes and Measures: The primary end point was excellent functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 1. All end points had blinded assessment and were analyzed on a full analysis set. Results: Among 1893 eligible patients with acute moderate ischemic stroke who were randomized (mean [SD] age, 65 [10.3] years; 606 women [34.1%]), 1776 (93.8%) completed the trial. The number with excellent functional outcome at 90 days was 582 (67.4%) in the RIC group and 566 (62.0%) in the control group (risk difference, 5.4% [95% CI, 1.0%-9.9%]; odds ratio, 1.27 [95% CI, 1.05-1.54]; P = .02). The proportion of patients with any adverse events was 6.8% (59/863) in the RIC group and 5.6% (51/913) in the control group. Conclusions and Relevance: Among adults with acute moderate ischemic stroke, treatment with remote ischemic conditioning compared with usual care significantly increased the likelihood of excellent neurologic function at 90 days. However, these findings require replication in another trial before concluding efficacy for this intervention. Trial Registration: ClinicalTrials.gov Identifier: NCT03740971.

Updated Confirmatory Diagnosis for Mucopolysaccharidoses in Taiwanese Infants and the Application of Gene Variants.

Mucopolysaccharidosis (MPS) is a lysosomal storage disease caused by genetic defects that result in deficiency of one specific enzyme activity, consequently impairing the stepwise degradation of glycosaminoglycans (GAGs). Except for MPS II, the other types of MPS have autosomal recessive inheritance in which two copies of an abnormal allele must be present in order for the disease to develop. In this study, we present the status of variant alleles and biochemistry results found in infants suspected of having MPS I, II, IVA, and VI. A total of 324 suspected infants, including 12 for MPS I, 223 for MPS II, 72 for MPS IVA, and 17 for MPS VI, who were referred for MPS confirmation from newborn screening centers in Taiwan, were enrolled. In all of these infants, one specific enzyme activity in dried blood spot filter paper was lower than the cut-off value in the first blood sample, as well asin a second follow-up sample. The confirmatory methods used in this study included Sanger sequencing, next-generation sequencing, leukocyte enzyme fluorometric assay, and GAG-derived disaccharides in urine using tandem mass spectrometry assays. The results showed that five, nine, and six infants had MPS I, II, and IVA, respectively, and all of them were asymptomatic. Thus, a laboratory diagnosis is extremely important to confirm the diagnosis of MPS. The other infants with identified nucleotide variations and reductions in leukocyte enzyme activities were categorized as being highly suspected cases requiring long-term and intensive follow-up examinations. In summary, the final confirmation of MPS depends on the most powerful biomarkers found in urine, i.e., the quantification of GAG-derived disaccharides including dermatan sulfate, heparan sulfate, and keratan sulfate, and analysis of genetic variants can help predict outcomes and guide treatment.

[Time-dependent injury of mouse cerebral cortex and hippocampus by acute hypoxia].

The aim of this study was to investigate the harmful effects of acute hypoxia on mouse cerebral cortex and hippocampus and the underlying mechanism. Mouse model of acute hypoxia was constructed by using a sealed glass jar. Laser speckle contrast imaging was used to detect the changes of cerebral blood flow after different time duration of hypoxia. Total superoxide dismutase (T-SOD) and malondialdehyde (MDA) assay kits were used to detect oxidative stress in cerebral cortex and hippocampus. Immunofluorescent staining was used to detect neuroinflammatory response of microglia in the cerebral cortex and hippocampus. One-step TUNEL method was used to detect neuronal apoptosis. The results showed that, compared with non-hypoxia (0 min hypoxia) group, 30 min hypoxia group exhibited decreased cerebral blood flow, higher percentage of CD68+/Iba1+ microglia, and increased neural apoptosis in the cerebral cortex and hippocampus. Compared with 30 min group, 60 min hypoxia group showed significantly decreased cerebral blood flow, increased MDA content in the cortex, as well as greater percentage of CD68+/Iba1+ microglia and neuronal apoptosis in the cerebral cortex and hippocampus. These results suggest that acute hypoxia damages brain tissue in a time-dependent manner and the oxidative stress and neuroinflammation are important mechanisms.

Bacterial mechanosensing: the force will be with you, always.

Whether bacteria are in the planktonic state, free-swimming or free-floating in liquid, or in the biofilm state, sessile on surfaces, they are always subject to mechanical forces. The long, successful evolutionary history of bacteria implies that they are capable of adapting to varied mechanical forces, and probably even actively respond to mechanical cues in their changing environments. However, the sensing of mechanical cues by bacteria, or bacterial mechanosensing, has been under-investigated. This leaves the mechanisms underlying how bacteria perceive and respond to mechanical cues largely unknown. In this Review, we first examine the surface-associated behavior of bacteria, outline the clear evidence for bacterial mechanosensing and summarize the role of flagella, type-IV pili, and envelope proteins as potential mechanosensors, before presenting indirect evidence for mechanosensing in bacteria. The general themes underlying bacterial mechanosensing that we highlight here may provide a framework for future research.