Cellular communication network factor 1 promotes retinal leakage in diabetic retinopathy via inducing neutrophil stasis and neutrophil extracellular traps extrusion.

BACKGROUND: Diabetic retinopathy (DR) is a major cause of blindness and is characterized by dysfunction of the retinal microvasculature. Neutrophil stasis, resulting in retinal inflammation and the occlusion of retinal microvessels, is a key mechanism driving DR. These plugging neutrophils subsequently release neutrophil extracellular traps (NETs), which further disrupts the retinal vasculature. Nevertheless, the primary catalyst for NETs extrusion in the retinal microenvironment under diabetic conditions remains unidentified. In recent studies, cellular communication network factor 1 (CCN1) has emerged as a central molecule modulating inflammation in pathological settings. Additionally, our previous research has shed light on the pathogenic role of CCN1 in maintaining endothelial integrity. However, the precise role of CCN1 in microvascular occlusion and its potential interaction with neutrophils in diabetic retinopathy have not yet been investigated. METHODS: We first examined the circulating level of CCN1 and NETs in our study cohort and analyzed related clinical parameters. To further evaluate the effects of CCN1 in vivo, we used recombinant CCN1 protein and CCN1 overexpression for gain-of-function, and CCN1 knockdown for loss-of-function by intravitreal injection in diabetic mice. The underlying mechanisms were further validated on human and mouse primary neutrophils and dHL60 cells. RESULTS: We detected increases in CCN1 and neutrophil elastase in the plasma of DR patients and the retinas of diabetic mice. CCN1 gain-of-function in the retina resulted in neutrophil stasis, NETs extrusion, capillary degeneration, and retinal leakage. Pre-treatment with DNase I to reduce NETs effectively eliminated CCN1-induced retinal leakage. Notably, both CCN1 knockdown and DNase I treatment rescued the retinal leakage in the context of diabetes. In vitro, CCN1 promoted adherence, migration, and NETs extrusion of neutrophils. CONCLUSION: In this study, we uncover that CCN1 contributed to retinal inflammation, vessel occlusion and leakage by recruiting neutrophils and triggering NETs extrusion under diabetic conditions. Notably, manipulating CCN1 was able to hold therapeutic promise for the treatment of diabetic retinopathy.

The Significance of the 98th Amino Acid in GP2a for Porcine Reproductive and Respiratory Syndrome Virus Adaptation in Marc-145 Cells.

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important pathogens in the pig industry. Marc-145 cells are widely used for PRRSV isolation, vaccine production, and investigations into virus biological characteristics. Despite their significance in PRRSV research, Marc-145 cells struggle to isolate specific strains of the North American virus genotype (PRRSV-2). The involvement of viral GP2a, GP2b, and GP3 in this phenomenon has been noted. However, the vital amino acids have not yet been identified. In this study, we increased the number of blind passages and successfully isolated two strains that were previously difficult to isolate with Marc-145 cells. Both strains carried an amino acid substitution in GP2a, specifically phenylalanine to leucine at the 98th amino acid position. Through a phylogenetic and epidemiologic analysis of 32 strains, those that were not amenable to isolation widely exhibited this mutation. Then, by using the PRRSV reverse genetics system, IFA, and Western blotting, we identified the mutation that could affect the tropism of PRRSV-2 for Marc-145 cells. Furthermore, an animal experiment was conducted. Through comparisons of clinical signs, mortality rates, and viral load in the organs and sera, we found that mutation did not affect the pathogenicity of PRRSV-2. In conclusion, our study firmly establishes the 98th amino acid in GP2a as a key determinant of PRRSV-2 tropism for Marc-145 cells.

Research on the Mechanical, Thermal and Induction Healing Properties of Asphalt Wearing Course with Steel Fibers.

Induction healing technology can effectively repair microcracks in asphalt mixtures and is a promising maintenance technology for asphalt pavements. However, it requires the addition of steel wool fibers to asphalt mixtures and cannot be directly used to repair existing pavements. In order to improve the practicality of the induction healing technology, this article designs a wearing course asphalt mixture with induction healing function that is going to be paved above the existing road surface. The AC-10 asphalt wearing course for induction heating was prepared by adding steel fiber (SF). Analysis of the overall temperature of the surface revealed the unevenness of the temperature distribution, and the healing properties were investigated through protective heating that controlled the maximum temperature of the upper surface. The results show that the addition of SF can improve the high-temperature stability, low-temperature and intermediate-temperature crack resistance, and moisture stability of asphalt wearing courses; however, it has adverse effects on volumetric performance and skid resistance. The heating temperature increases with the increase in SF content, but higher maximum temperature heating rate causes worse heating uniformity and lower healing effect. The maximum heating rate of the sample with 10% SF reaches 3.92 °C/s, while its heating rate at minimum temperature is similar to that of the sample with 6% SF, which is only 0.7 °C/s, indicating the worst heating uniformity. The best healing effect occurs when the maximum temperature of the upper surface reaches 160 °C. The recommended optimal SF content is 6% of the asphalt volume. The asphalt mixture with 6% SF has an appropriate volume performance, moisture stability, and skid resistance; additionally, it has the best high-temperature stability, as well as low-temperature and intermediate-temperature crack resistance. Meanwhile, it also has uniform temperature distribution and efficient healing efficiency.

A Portable, Integrated, Sample-In Result-Out Nucleic Acid Diagnostic Device for Rapid and Sensitive Chikungunya Virus Detection.

Chikungunya virus, a mosquito-borne virus that causes epidemics, is often misdiagnosed due to symptom similarities with other arboviruses. Here, a portable and integrated nucleic acid-based diagnostic device, which combines reverse transcription-loop-mediated isothermal amplification and lateral-flow detection, was developed. The device is simple to use, precise, equipment-free, and highly sensitive, enabling rapid chikungunya virus identification. The result can be obtained by the naked eye within 40 min. The assay can effectively distinguish chikungunya virus from dengue virus, Japanese encephalitis virus, Zika virus, and yellow fever virus with high specificity and sensitivity as low as 598.46 copies mL-1. It has many benefits for the community screening and monitoring of chikungunya virus in resource-limited areas because of its effectiveness and simplicity. The platform has great potential for the rapid nucleic acid detection of other viruses.

Nano-Enhanced Phase Reinforced Magnesium Matrix Composites: A Review of the Matrix, Reinforcement, Interface Design, Properties and Potential Applications.

Magnesium matrix composites are essential lightweight metal matrix composites, following aluminum matrix composites, with outstanding application prospects in automotive, aerospace lightweight and biomedical materials because of their high specific strength, low density and specific stiffness, good casting performance and rich resources. However, the inherent low plasticity and poor fatigue resistance of magnesium hamper its further application to a certain extent. Many researchers have tried many strengthening methods to improve the properties of magnesium alloys, while the relationship between wear resistance and plasticity still needs to be further improved. The nanoparticles added exhibit a good strengthening effect, especially the ceramic nanoparticles. Nanoparticle-reinforced magnesium matrix composites not only exhibit a high impact toughness, but also maintain the high strength and wear resistance of ceramic materials, effectively balancing the restriction between the strength and toughness. Therefore, this work aims to provide a review of the state of the art of research on the matrix, reinforcement, design, properties and potential applications of nano-reinforced phase-reinforced magnesium matrix composites (especially ceramic nanoparticle-reinforced ones). The conventional and potential matrices for the fabrication of magnesium matrix composites are introduced. The classification and influence of ceramic reinforcements are assessed, and the factors influencing interface bonding strength between reinforcements and matrix, regulation and design, performance and application are analyzed. Finally, the scope of future research in this field is discussed.

Mild hyperthermia enhanced synergistic uric acid degradation and multiple ROS elimination for an effective acute gout therapy.

BACKGROUND: Acute gouty is caused by the excessive accumulation of Monosodium Urate (MSU) crystals within various parts of the body, which leads to a deterioration of the local microenvironment. This degradation is marked by elevated levels of uric acid (UA), increased reactive oxygen species (ROS) production, hypoxic conditions, an upsurge in pro-inflammatory mediators, and mitochondrial dysfunction. RESULTS: In this study, we developed a multifunctional nanoparticle of polydopamine-platinum (PDA@Pt) to combat acute gout by leveraging mild hyperthermia to synergistically enhance UA degradation and anti-inflammatory effect. Herein, PDA acts as a foundational template that facilitates the growth of a Pt shell on the surface of its nanospheres, leading to the formation of the PDA@Pt nanomedicine. Within this therapeutic agent, the Pt nanoparticle catalyzes the decomposition of UA and actively breaks down endogenous hydrogen peroxide (H2O2) to produce O2, which helps to alleviate hypoxic conditions. Concurrently, the PDA component possesses exceptional capacity for ROS scavenging. Most significantly, Both PDA and Pt shell exhibit absorption in the Near-Infrared-II (NIR-II) region, which not only endow PDA@Pt with superior photothermal conversion efficiency for effective photothermal therapy (PTT) but also substantially enhances the nanomedicine's capacity for UA degradation, O2 production and ROS scavenging enzymatic activities. This photothermally-enhanced approach effectively facilitates the repair of mitochondrial damage and downregulates the NF-κB signaling pathway to inhibit the expression of pro-inflammatory cytokines. CONCLUSIONS: The multifunctional nanomedicine PDA@Pt exhibits exceptional efficacy in UA reduction and anti-inflammatory effects, presenting a promising potential therapeutic strategy for the management of acute gout.

Upgraded and Light-Up Biosensing Platform: Entropy-Driven Catalysis Circuit Manipulates the Configuration Transformation of Novel DNA Silver Nanoclusters on the Graphene Oxide Surface.

To tackle the predicament of the traditional turn-off mechanism, exploring an activated turn-on system remains an intriguing and crucial objective in biosensing fields. Herein, a dark DNA Ag nanocluster (NC) with hairpin-structured DNA containing a six-base cytosine loop (6C loop) as a template is atypically synthesized. Intriguingly, the dark DNA Ag NCs can be lit to display strong red-emission nanoclusters. Building upon these exciting findings, an unprecedented and upgraded turn-on biosensing system [entropy-driven catalysis circuit (EDCC)-Ag NCs/graphene oxide (GO)] has been created, which employs an EDCC to precisely manipulate the conformational transition of DNA Ag NCs on the GO surface from adsorption to desorption. Benefiting from the effective quenching of GO and signal amplification capability of the EDCC, the newly developed EDCC-Ag NCs/GO biosensing system displays a high signal-to-background (S/B) ratio (26-fold) and sensitivity (limit of detection as low as 0.4 pM). Meanwhile, it has good specificity, excellent stability, and reliability in both buffer and biological samples. To the best of our knowledge, it is the first example that adopts an EDCC to precisely modulate the configuration transformation of DNA Ag NCs on the GO surface to obtain a biosensor with low background, strong fluorescence, high contrast, and sensitivity. This exciting finding may provide a new route to fabricate a novel turn-on biosensor based on hairpin-templated DNA Ag NCs in the optical imaging and bioanalytical fields.

Technological advances and challenges of reclaimed asphalt pavement (RAP) application in road engineering-a bibliometric analysis from 2000 to 2022.

Reclaimed asphalt pavement (RAP) is a valuable material that can be recycled and reused in road engineering to reduce environmental impact, resource utilization, and economic costs. However, the application of RAP in road engineering presents both opportunities and challenges. This study visually analyzes the knowledge background, research status, and latest knowledge structure of literature related to RAP using scientific metric methods such as VOSviewer and Citespace. The Web of Science (WoS) core collection database identified 2963 research publications from 2000 to 2022. Collaborative networks between highly cited references, journals, authors, academic institutions, countries, and funding organizations are analyzed in this study, along with a co-occurrence analysis of keywords for the RAP research publications. Results showed that the USA has long been a leader in RAP research, China surpassed the USA in annual publication output in 2019, increasing from 2 publications in 2002 to 177 publications in 2022, and has made significant investments in technological aspects. Chang'an University ranked first in total publication output (131 publications, 4.4%). Current major research themes include road performance, recycling technology, regeneration mechanisms, and the life cycle assessment of RAP. In addition, based on cluster analysis of keywords, text content analysis, and SWOT analysis, this study also discusses RAP's challenges and future development directions in road engineering. These findings provide scholars with valuable information to gain insight into technological advances and challenges in the field of RAP.

Seismic performance of soft soil foundation with a new type of assembled wall tuned mass damper.

The design of tuned mass damper (TMD) parameters is influenced by the soil-structure-TMD coupling system; thus, it is important to consider the soil-structure interaction (SSI) for the vibration control effect of the TMD. Recently, the acquisition of TMD parameters considering soil-structure interactions has only remained at the theoretical stage, lacking relevant experimental verification. Traditional TMD face the problems of occupying a large building space, increasing construction costs, and non-replaceable components. In this study, an assembled wall-type damping TMD was designed. By comparing the dynamic response of the uncontrolled and controlled structures equipped with the newly assembled wall-type damping TMD in the shaking table test on a soft soil foundation, we analyzed whether the SSI effect was considered in the TMD design parameters on the damping effect of the newly assembled wall-type tuned mass damper. The TMD parameters optimized using the artificial intelligence algorithm were verified experimentally. The results indicated that the traditional TMD design parameters were discordant because the SSI effect was not considered. The SSI effect in the soil effectively reduces the dynamic response of the superstructure. By considering the SSI effect and improving the multi-population genetic algorithm, a wall-type damping TMD with optimized parameters can achieve a good damping effect.

Modified double-pulley fixation provides better reduction of bone fragments and union compared to single-point fixation in bony Bankart lesions.

PURPOSE: The purpose of this study was to compare clinical scores and imaging outcomes of bony Bankart lesions that underwent single-point and modified double-pulley fixation after at least 2 years of follow-up. METHODS: Patients who underwent surgery to treat bony Bankart injuries were included and divided into groups A and B. A total of 69 patients were included (32 in group A and 37 in group B). Patients in group A underwent arthroscopic modified double-pulley fixation and patients in group B underwent arthroscopic single-point fixation. Three-dimensional computed tomography (3D-CT) was used to assess glenoid reduction one day after surgery. Postoperative bony union was assessed using 3D-CT and multiplanar reconstruction images 6 months after surgery. Constant-Murley, Rowe rating system, visual analogue scale and University of California at Los Angeles and American Shoulder and Elbow Surgeons scores were recorded before and after surgery. RESULTS: In terms of imaging measurements, there was no significant group difference in the preoperative size of the glenoid defect, the size of the bony fragment or the expected postoperative size of the glenoid defect. The sizes of the actual postoperative glenoid defects differed significantly between the groups (p = 0.027), as did the absolute difference between the expected and actual glenoid defect sizes (p < 0.001). At 6 months postoperatively, 50.0% of group A patients and 24.3% of group B patients exhibited complete bony union (p = 0.027); the rates of partial union were 37.5% and 56.8%, respectively. At the final follow-up, all clinical scores were significantly better than the preoperative scores (all p < 0.05), with no significant group differences (not significant). CONCLUSIONS: The use of the modified double-pulley technique with two anchors to treat bony Bankart injuries provides a better reduction of bone fragments than single-point fixation with two anchors and was associated with a higher rate of early bone union. LEVEL OF EVIDENCE: Level III.

Microsatellite Instability Detection in Cancer: A Multiplex qPCR Approach that Obviates the Need for Matching Normal Samples.

BACKGROUND: Microsatellite instability (MSI) indicates DNA mismatch repair deficiency in certain types of cancer, such as colorectal cancer. The current gold standard technique, PCR-capillary electrophoresis (CE), requires matching normal samples and specialized instrumentation. We developed VarTrace, a rapid and low-cost quantitative PCR (qPCR) assay, to evaluate MSI using solely the tumor sample DNA, obviating the requirement for matching normal samples. METHODS: One hundred and one formalin-fixed paraffin-embedded (FFPE) tumor samples were tested using VarTrace and compared with the Promega OncoMate assay utilizing PCR-CE. Tumor percentage limit of detection was evaluated on contrived samples derived from clinical high MSI (MSI-H) samples. Analytical sensitivity, specificity, limit of detection, and input requirements were assessed using synthetic commercial reference standards. RESULTS: VarTrace successfully analyzed all 101 clinical FFPE samples, demonstrating 100% sensitivity and 98% specificity compared to OncoMate. It detected MSI-H with 97% accuracy down to 10% tumor. Analytical studies using synthetic samples showed a limit of detection of 5% variant allele frequency and a limit of input of 0.5 ng. CONCLUSIONS: This study validates VarTrace as a swift, accurate, and economical assay for MSI detection in samples with low tumor percentages without the need for matching normal DNA. VarTrace's capacity for highly sensitive MSI analysis holds potential for enhancing the efficiency of clinical work flows and broadening the availability of this test.

Soybean steroids improve crop abiotic stress tolerance and increase yield.

Sterols have long been associated with diverse fields, such as cancer treatment, drug development, and plant growth; however, their underlying mechanisms and functions remain enigmatic. Here, we unveil a critical role played by a GmNF-YC9-mediated CCAAT-box transcription complex in modulating the steroid metabolism pathway within soybeans. Specifically, this complex directly activates squalene monooxygenase (GmSQE1), which is a rate-limiting enzyme in steroid synthesis. Our findings demonstrate that overexpression of either GmNF-YC9 or GmSQE1 significantly enhances soybean stress tolerance, while the inhibition of SQE weakens this tolerance. Field experiments conducted over two seasons further reveal increased yields per plant in both GmNF-YC9 and GmSQE1 overexpressing plants under drought stress conditions. This enhanced stress tolerance is attributed to the reduction of abiotic stress-induced cell oxidative damage. Transcriptome and metabolome analyses shed light on the upregulation of multiple sterol compounds, including fucosterol and soyasaponin II, in GmNF-YC9 and GmSQE1 overexpressing soybean plants under stress conditions. Intriguingly, the application of soybean steroids, including fucosterol and soyasaponin II, significantly improves drought tolerance in soybean, wheat, foxtail millet, and maize. These findings underscore the pivotal role of soybean steroids in countering oxidative stress in plants and offer a new research strategy for enhancing crop stress tolerance and quality from gene regulation to chemical intervention.

Association between urinary BTEX metabolites and dyslexic odds among school-aged children.

Benzene, toluene, ethylbenzene, and xylene (BTEX) are ubiquitous in the environment, and all of them can cause neurotoxicity. However, the association between BTEX exposure and dyslexia, a disorder with language network-related regions in left hemisphere affected, remains unclear. We aimed to assess the relationship between BTEX exposure and dyslexic odds among school-aged children. A case-control study, including 355 dyslexics and 390 controls from three cities in China, was conducted. Six BTEX metabolites were measured in their urine samples. Logistic regression model was used to explore the association between the BTEX metabolites and the dyslexic odds. Urinary trans,trans-muconic acid (MU: a metabolite of benzene) was significantly associated with an increased dyslexic odds [odds ratio (OR) = 1.23, 95% confidence interval (CI): 1.01, 1.50], and the adjusted OR of the dyslexic odds in the third tertile was 1.72 (95% CI: 1.06, 2.77) compared to that in the lowest tertile regarding urinary MU concentration. Furthermore, the association between urinary MU level and the dyslexic odds was more pronounced among children from low-income families based on stratified analyses. Urinary metabolite levels of toluene, ethylbenzene, and xylene were not found to be associated with the dyslexic odds. In summary, elevated MU concentrations may be associated with an increased dyslexic odds. We should take measures to reduce MU related exposure among children, particularly those with low family income.

Clinical characteristics of ulcerative colitis patients with different types of Helicobacter pylori infection.

There has been a suggestion of a potential protective effect of Helicobacter pylori (H. pylori) in the development of ulcerative colitis (UC). Virulence factor is an important factor in H. pylori, but little is known about the clinical characteristics of ulcerative colitis. In this retrospective study, a total of 322 patients with UC were analyzed. They were divided into three groups based on H. pylori antibody typing classification: type I H. pylori infection group, type II H. pylori infection group, and H. pylori-negative group. The study aimed to analyze the clinical characteristics of different types of H. pylori infection groups. The proportions of disease course, nationality, clinical type, and disease severity among UC patients in different types of H. pylori infection groups exhibited statistically significant differences (P < 0.05). However, no significant differences were observed in terms of sex, age, smoking status, alcohol consumption, body mass index (BMI), or lesion range (P > 0.05). Among the extraintestinal manifestations, the incidence of joint lesions in the type I H. pylori infection group was significantly lower compared with H. pylori-negative group (P < 0.05). The levels of red blood cell, hemoglobin, packed cell volume, albumin, A/G, and alanine aminotransferase were significantly higher in the type I H. pylori infection group compared with both the type II H. pylori infection group and H. pylori-negative group in the hematology index. Conversely, the levels of D-Dimer, C-reactive protein, and erythrocyte sedimentation rate were significantly lower in the type II H. pylori infection group (P < 0.05). In patients with UC, infections with the highly virulent type I H. pylori exhibit a negative correlation with both the severity of the disease and extraintestinal manifestations. While infections with the less virulent type II H. pylori are negatively correlated only with the disease severity. Therefore, the virulence factors of H. pylori play an important role in the regulation of UC. IMPORTANCE: The number of patients with ulcerative colitis (UC) has increased dramatically worldwide, posing a global public health challenge, There has been a suggestion of a potential protective effect of Helicobacter pylori in the development of UC. Virulence factor is an important factor in H. pylori, but high-quality clinical evidence is lacking. This study comprehensively analyzed the clinical characteristics of UC patients with different types of H. pylori infection. Infections with the highly virulent type I H. pylori are found to be negatively correlated with the severity of the disease as well as extraintestinal manifestations, whereas infections with the less virulent type II H. pylori demonstrate a negative correlation solely with disease severity. These results suggest that the virulence factors of H. pylori play a pivotal role in UC. Consequently, virulence factors should be taken into consideration when targeting H. pylori eradication in clinical practice, particularly in UC patients. It is crucial to evaluate the individual benefits to optimize personalized eradication therapies.

Longitudinal Associations Between Physical Activity and Depressive Symptoms in Chinese Children: Evidence from the Tongji Mental Health Cohort Study.

BACKGROUND: We aimed to examine the associations between depressive symptoms and physical activity parameters (e.g., intensity, frequency, and duration) among Chinese school-aged children. METHOD: Participants in this study were extracted from the Tongji Mental Health Cohort Study. The baseline survey was conducted in June 2020 involving 2588 school-aged children from two primary schools in Hubei Province, China. A total of 2435 children were followed up successfully in December 2020. The Children's Depression Inventory Short Form (CDI-S) was applied to evaluate depressive symptoms among school-aged children. The Physical Activity Rating Scale-3 (PARS-3) was adopted to estimate children's physical activity parameters including the intensity, frequency, and duration. Generalized estimation equation models were used to explore the longitudinal associations between physical activity and depressive symptoms among school-aged children. RESULTS: Engaging in moderate levels of physical activity (OR, 0.800; 95%CI, 0.692-0.924) or high levels of physical activity (OR, 0.808; 95%CI, 0.689-0.947) in the baseline survey was associated with a reduced risk of developing depressive symptoms in the follow-up survey compared with children engaging in low levels of physical activity. Stratified analyses revealed that the associations between physical activity and depressive symptoms exhibited a significant correlation among boys and children in the older age group (11-12 years). Our findings showed that engaging in physical activity more than once a week, with each session lasting 20 min or longer, was related to significant reductions in depressive symptoms by 43.8% and 22.3%, respectively. CONCLUSION: Self-reported physical activity is positively associated with improved mental health among Chinese school-aged children, especially when considering parameters such as frequency and duration. The association between vigorous-intensity physical activity and depressive symptoms in children should be cautiously interpreted. Future research should continue to explore the effects of vigorous-intensity physical activity on depressive symptoms in children.

Heterojunction of MXenes and MN4-graphene: Machine learning to accelerate the design of bifunctional oxygen electrocatalysts.

Oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) are essential for the development of excellent bifunctional electrocatalysts, which are key functions in clean energy production. The emphasis of this study lies in the rapid design and investigation of 153 MN4-graphene (Gra)/ MXene (M2NO) electrocatalysts for ORR/OER catalytic activity using machine learning (ML) and density functional theory (DFT). The DFT results indicated that CoN4-Gra/Ti2NO had both good ORR (0.37 V) and OER (0.30 V) overpotentials, while TiN4-Gra/M2NO and MN4-Gra/Cr2NO had high overpotentials. Our research further indicated orbital spin polarization and d-band centers far from the Fermi energy level, affecting the adsorption energy of oxygen-containing intermediates and thus reducing the catalytic activity. The ML results showed that the gradient boosting regression (GBR) model successfully predicted the overpotentials of the monofunctional catalysts RhN4-Gra/Ti2NO (ORR, 0.39 V) and RuN4-Gra/W2NO (OER, 0.45 V) as well as the overpotentials of the bifunctional catalyst RuN4-Gra/W2NO (ORR, 0.39 V; OER, 0.45 V). The symbolic regression (SR) algorithm was used to construct the overpotential descriptors without environmental variable features to accelerate the catalyst screening and shorten the trial-and-error costs from the source, providing a reliable theoretical basis for the experimental synthesis of MXene heterostructures.

Unraveling the mechanism of norfloxacin removal and fate of antibiotics resistance genes (ARGs) in the sulfur-mediated autotrophic denitrification via metagenomic and metatranscriptomic analyses.

The co-contamination of antibiotics and nitrogen has attracted widespread concerns due to its potential harm to ecological safety and human health. Sulfur-driven autotrophic denitrification (SAD) with low sludge production rate was adopted to treat antibiotics laden-organic deficient wastewater. Herein, a lab-scale sequencing batch reactor (SBR) was established to explore the simultaneous removal of nitrate and antibiotics, i.e. Norfloxacin (NOR), as well as microbial response mechanism of SAD sludge system towards NOR exposure. About 80.78 % of NOR was removed by SAD sludge when the influent NOR level was 0.5 mg/L, in which biodegradation was dominant removal route. The nitrate removal efficiency decreased slightly from 98.37 ± 0.58 % to 96.58 ± 1.03 % in the presence of NOR. Thiobacillus and Sulfurimonas were the most abundant sulfur-oxidizing bacteria (SOB) in SAD system, but Thiobacillus was more sensitive to NOR. The up-regulated genes related to Xenobiotics biodegradation and metabolism and CYP450 indicated the occurrence of NOR biotransformation in SAD system. The resistance of SAD sludge to the exposure of NOR was mainly ascribed to antibiotic efflux. And the effect of antibiotic inactivation was enhanced after long-term fed with NOR. The NOR exposure resulted in the increased level of antibiotics resistance genes (ARGs) and mobile genetic elements (MGEs). Besides, the enhanced ARG-MGE co-existence patterns further reveals the higher horizontal mobility potential of ARGs under NOR exposure pressures. The most enriched sulfur oxidizing bacterium Thiobacillus was a potential host for most of ARGs. This study provides a new insight for the treatment of NOR-laden wastewater with low C/N ratio based on the sulfur-mediated biological process.

The Efficacy of Adalimumab in Children with Chronic Non-infectious Posterior Uveitis and Panuveitis: A Retrospective Cohort Study.

INTRODUCTION: This study aimed to assess the efficacy and safety of adalimumab in pediatric patients with chronic non-infectious posterior uveitis and panuveitis (not associated with juvenile idiopathic arthritis). METHODS: The medical records of children (< 18 years old) with chronic non-infectious posterior uveitis and panuveitis were collected and analyzed in this retrospective cohort study. Children were allocated to a conventional adalimumab-free treatment (CT) or adalimumab (ADA) group based on whether they additionally received adalimumab. RESULTS: In total, 69 children (138 eyes) were included, with 21 (42 eyes) and 48 (96 eyes) in the CT and ADA groups, respectively. During the average follow-up period of 24 months, the improvement in all ocular parameters (best-corrected visual acuity, intraocular inflammation, fluorescein angiography score) was better in the ADA group than in the CT group, except for changes in central macular thickness, which did not significantly differ between the groups. The mean time of first alleviation, which was after 1.03 ± 0.12 months of therapy, was earlier in the ADA group than in the CT group (2.30 ± 0.46 months). In the ADA group, 90.6% of children had remission within 3 months, and 47.9% had no relapse during follow-up. Cough and cold were the most common adverse events in the ADA group; however, the number of adverse events was similar between both the groups. CONCLUSIONS: Adalimumab was effective in the treatment of chronic noninfectious posterior uveitis and panuveitis in pediatric patients, and disease inactivity was accomplished in the majority of the patients, thereby improving visual outcomes and maintaining disease stability. Adverse events were limited and tolerable.

Trends of Drug-Resistant Tuberculosis in an Urban and a Rural Area in China: A 10-Year Population-Based Molecular Epidemiological Study.

Objective: Drug resistance is the critical determinant for appropriate tuberculosis (TB) treatment regimens and an important indicator of the local TB burden. We aimed to investigate and compare trends in TB drug resistance in the urban Songjiang District of Shanghai from 2011 to 2020, and the rural Wusheng County of Sichuan Province from 2009 to 2020, to assess the effectiveness of local TB control and treatment programs. Methods: Whole-genome sequencing data of Mycobacterium tuberculosis were used to predict drug-resistance profiles and identify genomic clusters. Clustered, retreated cases of drug-resistant TB with identical resistance mutations, as well as all new resistant cases, were defined as transmitted resistance. The Cochran-Armitage trend test was used to identify trends in the proportions. Differences between groups were tested using the Wilcoxon rank sum or chi-square tests. Results: The annual proportions of rifampicin-resistant (RR), isoniazid-resistant (INH-R) and multidrug-resistant (MDR) TB cases did not change significantly in Songjiang. In Wusheng, however, the percentage of total TB cases that were RR decreased from 13.2% in 2009 to 3.7% in 2020, the INH-R cases decreased from 16.5% to 7.3%, and the MDR cases decreased from 10.7% to 3.7%. In retreated cases, the percentage of drug resistance decreased in both Songjiang and Wusheng, suggesting improved treatment programs. Transmitted resistance accounted for more than two thirds of drug-resistant cases over the entire study periods, and in recent years this proportion has increased significantly in Songjiang. Conclusion: In both urban Songjiang and rural Wusheng, drug-resistant TB is mostly the result of transmission of drug resistant strains and the percentage of transmitted resistance will likely increase with on-going improvements in the TB treatment programs. Reducing the prevalence of drug resistance depends principally upon decreasing transmission through the prompt diagnosis and effective treatment of drug-resistant TB cases.