[Spatial Distribution Characteristics of PM2.5 and O3 in Beijing-Tianjin-Hebei Region Based on Time Series Decomposition].

Notably, clear spatial differences occur in the distribution of air pollution among cities in the Beijing-Tianjin-Hebei (BTH) Region. Clarifying the concentration distribution of PM2.5 and O3 at different time scales is helpful to formulate scientific and effective pollution prevention and control measures. Here, the concentrations of PM2.5 and O3 were decomposed using a seasonal-trend decomposition procedure based on the loess (STL) method; their long-term, seasonal, and short-term components were obtained; and their temporal and spatial distribution characteristics were studied. The results showed that the decrease in PM2.5 concentration in the BTH Region from 2017 to 2021 was higher than that of O3. There was a positive correlation between PM2.5 and O3 concentrations in spring and summer and a negative correlation in autumn and winter. The short-term component and seasonal component had the greatest contribution to PM2.5 and O3 concentrations, respectively. There were two principal components in the seasonal and short-term components of PM2.5 and the long-term and short-term components of O3, corresponding to the central and southern part of Hebei Province and the northern part of the BTH Region. Sub-regional distribution of PM2.5 and O3 in the BTH Region at different time scales were found. Compared with that in the original series, the long-term component could better reflect the evolution trend of PM2.5 and O3 concentrations, and the standard deviation (SD) of the seasonal component and short-term component could be used to measure the fluctuation in PM2.5 and O3 concentrations in various cities. The SD of the seasonal and short-term components of the PM2.5 concentration in every city in front of Taihang Mountain was higher, and the SD of the short-term component of the O3 concentration in Tangshan was the highest.

[Source and Cause Analysis of High Concentration of Inorganic Aerosol During Two Typical Pollution Processes in Winter over Tianjin].

Inorganic aerosol is the main component of haze days in winter over Tianjin. In this study, two typical high concentrations of secondary inorganic aerosol (SIA) processes, defined as CASE1 and CASE2, were selected during polluted days in January 2020 over Tianjin, and the effects of meteorological factors, regional transport, and chemical processes were comprehensively investigated combined with observations and numerical models (WRF-NAQPMS). The average SIA concentrations in CASE1 and CASE2 were 76.8 µg·m-3 and 66.0 µg·m-3, respectively, and the nitrate concentration was higher than that of sulfate and ammonium, which were typical nitrate-dominated pollution processes. Meteorological conditions played a role in inorganic aerosol formation. The temperature of approximately -6-0℃ and 2-4℃ and the relative humidity of 50%-60% and 80%-100% would be suitable conditions for the high SIA concentration (>80 µg·m-3) in CASE1, whereas the temperature of approximately 2-4℃ and the relative humidity of 60%-70% would be suitable in CASE2. The average contribution rates of external sources to SIA in the CASE1 and CASE2 processes were 62.3% and 22.1%, which were regional transport-dominant processes and local emission-dominant processes, respectively. The contribution of the local emission of CASE1 to nitrate and sulfate was 16.2 µg·m-3 and 8.2 µg·m-3, respectively, higher than that of external sources (31.7 µg·m-3 and 8.8 µg·m-3). the local contribution of CASE2 to nitrate and sulfate was 29.3 µg·m-3 and 25.1 µg·m-3, respectively, whereas the contribution from external sources was 8.1 µg·m-3 and 9.4 µg·m-3, respectively. The quantitative result indicated that local formation and regional transport resulted in higher nitrate concentration than sulfate in CASE1, in contrast to only local sources in CASE2. The gas phase reaction was the main source of inorganic aerosol formation, contributing 48.9% and 57.8% in CASE1 and CASE2, respectively, whereas the heterogeneous reactions were also important processes, with contribution rates of 48.1% and 42.2% to SIA. The effect of aqueous phase reaction was negligible.

Efficacy and safety of bimekizumab in the treatment of psoriatic arthritis: a systematic review and meta-analysis.

BACKGROUND: Bimekizumab, a humanized monoclonal IgG1 antibody targeting both interleukin (IL)-17A and IL-17F, could be effective for treating Psoriatic arthritis (PsA). This study aimed to systematically evaluate the efficacy and safety of bimekizumab in the management of PsA. RESEARCH DESIGN AND METHODS: A comprehensive literature search by August 2023 was performed through PubMed, Embase, Cochrane Controlled Register of Trials, and ClinicalTrials.gov. investigating the efficacy or safety data of bimekizumab in the treatment of PsA. Data was pooled using the random-effects models. Egger tests were used to evaluate potential publication bias. RESULTS: A total of 4 RCTs, involving 892 PsA patients and 467 placebo controls, were included in this analysis. Bimekizumab significantly increased the rates of PASI75 and PASI100 compared with placebos [RR = 7.22, 95% CI (5.24, 9.94), p < 0.001; RR = 10.12, 95% CI (6.00, 17.09), p < 0.001]. The rate of overall adverse events was slightly higher in the bimekizumab group [RR = 1.42, 95% CI (1.05, 1.93) p = 0.023). However, there were fewer adverse severe drug reactions in the bimekizumab group compared to the placebo. CONCLUSION: Bimekizumab had a significant clinical benefit in managing PsA and an acceptable safety profile.

Exploring the therapeutic potential of regulatory T cell in rheumatoid arthritis: Insights into subsets, markers, and signaling pathways.

Rheumatoid arthritis (RA) is a complex autoimmune inflammatory rheumatic disease characterized by an imbalance between immunological reactivity and immune tolerance. Regulatory T cells (Tregs), which play a crucial role in controlling ongoing autoimmunity and maintaining peripheral tolerance, have shown great potential for the treatment of autoimmune inflammatory rheumatic diseases such as RA. This review aims to provide an updated summary of the latest insights into Treg-targeting techniques in RA. We focus on current therapeutic strategies for targeting Tregs based on discussing their subsets, surface markers, suppressive function, and signaling pathways in RA.

Genetic prediction of modifiable lifestyle factors for erectile dysfunction.

Background: The causal relationship between certain lifestyle factors and erectile dysfunction (ED) is still uncertain. Aim: The study sought to investigate the causal effect of 9 life factors on ED through 2-sample single-variable Mendelian randomization (SVMR) and multivariable Mendelian randomization (MVMR). Methods: Genetic instruments to proxy 9 risk factors were identified by genome-wide association studies. The genome-wide association studies estimated the connection of these genetic variants with ED risk (n = 223 805). We conducted SVMR, inverse variance-weighting, Cochran's Q, weighted median, MR-Egger, MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier), and MVMR analyses to explore the total and direct relationship between life factors and ED. Outcomes: The primary outcome was defined as self or physician-reported ED, or using oral ED medication, or a history of surgery related to ED. Results: In SVMR analyses, suggestive associations with increased the risk of ED were noted for ever smoked (odds ratio [OR], 5.894; 95% confidence interval [CI], 0.469 to 3.079; P = .008), alcohol consumption (OR, 1.495; 95% CI, 0.044 to 0.760; P = .028) and body mass index (BMI) (OR, 1.177; 95% CI, 0.057 to 0.268; P = .003). Earlier age at first intercourse was significantly related to reduced ED risk (OR, 0.659; 95% CI, -0.592 to -0.244; P = 2.5 × 10-6). No strong evidence was found for the effect of coffee intake, time spent driving, physical activity, and leisure sedentary behaviors on the incidence of ED (All P > .05). The result of MVMR analysis for BMI (OR, 1.13; 95% CI, 1.01 to 1.25; P = .045) and earlier age at first intercourse (OR, 0.77; 95% CI, 0.56 to 0.99; P = .018) provided suggestive evidence for the direct impact on ED, while no causal factor was detected for alcoholic drinks per week and ever smoked. Clinical implications: This study provides evidence for the impact of certain modifiable lifestyle factors on the development of ED. Strengths and limitations: We performed both SVMR and MVMR to strengthen the causal relationship between exposures and outcomes. However, the population in this study was limited to European ancestry. Conclusion: Ever smoked, alcoholic drinks per week, BMI, and age first had sexual intercourse were causally related to ED, while the potential connection between coffee intake, physical activity, recreational sedentary habits, and increased risk of ED needs to be further confirmed.

Longitudinal change of intrinsic capacity and associated factors in older Chinese adults: China Health and Retirement Longitudinal Study.

BACKGROUND: Although intrinsic capacity (IC) has been constructed in older populations, whether IC retains the same structure over time has not been formally examined, nor have the factors associated with the changes in IC over time been thoroughly investigated. This study aimed to establish that the structure of IC remains unchanged over time by testing its longitudinal measurement invariance and to investigate factors that influence the longitudinal change of IC over time. METHODS: Data came from 7,271 participants aged 60 and older from the China Health and Retirement Longitudinal Study in 2011 (Wave 1) and 2015 (Wave 3). Bifactor confirmatory factor analysis (CFA) was used to construct IC with its domains, and the longitudinal measurement invariance of IC between Waves was tested. RESULTS: Bifactor CFA fitted the data well at both Waves and showed good construct validity. Partial scalar invariance was supported with non-invariant intercepts for delayed word recall, math, and close vision. Decreases in IC were associated with increasing age, being female (-0.030, 95% CI: -0.045, -0.016), living in rural areas (-0.019, 95% CI: -0.030, -0.009), BMI < 18.5 (-0.019, 95% CI: -0.035, -0.003), and hypertension (-0.012, 95% CI: -0.022, -0.001). Increases in IC were associated with higher education (primary school: 0.012, 95% CI: 0.001, 0.024; lower secondary school: 0.023, 95% CI: 0.005, 0.041) and drinking ≥4/week (0.019, 95% CI: 0.003, 0.034). Stratifying the sample by gender, the protective effect of education was observed only in women. CONCLUSIONS: The bifactor structure of the IC construct was valid and retained its meaning over time. Longitudinal changes in IC were associated with various sociodemographic factors, lifestyle, and health conditions, confirming the need to monitor IC for timely intervention, particularly in those with risk factors for IC decline.

The outcome of combined use of iRoot BP Plus and iRoot SP for root-end filling in endodontic microsurgery: a randomized controlled trial.

OBJECTIVES: Root-end filling is important for the clinical outcome of endodontic microsurgery. Our previous study showed that combined application of iRoot BP Plus Root Repair Material (BP-RRM) and iRoot SP Injectable Root Canal Sealer (SP-RCS) in root-end filling exhibited better apical sealing as compared to the application of BP-RRM alone. The aim of this randomized controlled clinical trial was to evaluate the effect of the combined use of BP-RRM and SP-RCS on the prognosis of teeth with refractory periapical diseases after endodontic microsurgery. MATERIALS AND METHODS: 240 teeth with refractory periapical diseases scheduled for endodontic microsurgery were randomly divided into BP-RRM/SP-RCS group (n = 120) and BP-RRM group (n = 120). The patients were followed up at 3 months, 6 months, and 12 months after endodontic microsurgery. Pre- and post-operative clinical and radiographic examinations were performed to evaluate the treatment outcome. The 1-year success rate of endodontic microsurgery in BP-RRM/SP-RCS and BP-RRM groups was compared by Chi-square test. Factors that might impact the prognosis were further analyzed using Chi-square test or Fisher's exact test. RESULTS: A total of 221 teeth completed the 12-month follow-up. The 1-year success rates of the BP-RRM/SP-RCS and BP-RRM groups were 94.5% (104/110) and 92.8% (103/111), respectively. The combined use of BP-RRM and SP-RCS achieved a clinical outcome comparable to BP-RRM alone (P = 0.784). Tooth type (P = 0.002), through-and-through/apico-marginal lesion (P = 0.049), periodontal status (P < 0.0001), and Kim's lesion classification (P < 0.0001) were critical factors associated with the 1-year success of endodontic microsurgery. CONCLUSIONS: The combined use of BP-RRM and SP-RCS is a practicable method for root-end filling in endodontic microsurgery with a satisfactory 1-year clinical outcome. CLINICAL RELEVANCE: The combined application of BP-RRM and SP-RCS in EMS is an effective root-end filling method with a satisfactory 1-year clinical outcome. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (ChiCTR2100052174).

Expert consensus on difficulty assessment of endodontic therapy.

Endodontic diseases are a kind of chronic infectious oral disease. Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha. However, it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy (RCT). Recent research, encompassing bacterial etiology and advanced imaging techniques, contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT. Success in RCT hinges on factors like patients, infection severity, root canal anatomy, and treatment techniques. Therefore, improving disease management is a key issue to combat endodontic diseases and cure periapical lesions. The clinical difficulty assessment system of RCT is established based on patient conditions, tooth conditions, root canal configuration, and root canal needing retreatment, and emphasizes pre-treatment risk assessment for optimal outcomes. The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT. These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

Efficacy and Safety of Risankizumab in Patients with Psoriatic Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Currently, the cause of psoriatic arthritis (PsA) is unknown, and the effectiveness of current drug treatments is unsatisfactory. In March 2019, the US Food and Drug Administration (FDA) approved risankizumab, a humanized immunoglobulin G1 (IgG1) monoclonal antibody targeting the p19 subunit of interleukin (IL)-23, for the treatment of PsA in adults. This study aimed to conduct a meta-analysis of double-blind, randomized, placebo-controlled trials to evaluate the effectiveness and safety of risankizumab in moderate-to-severe PsA. METHODS: We conducted a thorough search of relevant databases from the establishment of the databases to October 1, 2023. We conducted a meta-analysis using Stata 12.0 and utilized I2 and Egger tests to assess heterogeneity and publication bias among the studies. Bias assessment was performed using the risk bias map and bias risk summary diagram generated by Revman5.4 software. The review protocols were registered on PROSPERO (CRD42023451894) and adhered to the preferred reporting item of system evaluation (PRISMA) guideline. RESULTS: Six randomized controlled trials (RCTs) involving 5038 patients with PsA treated with either risankizumab or placebo were included in the analysis. At 24 weeks, the risankizumab group demonstrated a significantly higher American College of Rheumatology-20 (ACR20) response rate compared to the placebo group (RR 1.760, 95% CI 1.568-1.977, P < 0.001). Additionally, the risankizumab group showed a significantly higher Minimal Disease Activity (MDA) response rate compared to the placebo group (RR 1.827, 95% CI 1.048-3.184, P < 0.05). The risankizumab group also exhibited improvement in Short Form 36 Questionnaire (SF-36) score (SMD 0.51, 95% CI 0.33-0.69, P < 0.001), with significantly lower Health Assessment Questionnaire Disability Index (HAQ-DI) score (SMD - 0.27, 95% CI - 0.37 to - 0.17, P < 0.001) and higher Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score (SMD 0.27, 95% CI 0.20-0.35, P < 0.001) compared to the placebo group. Moreover, the risankizumab group had a significantly lower Psoriasis Area and Severity Index (PASI) score (SMD - 6.12, 95% CI - 10.02 to 2.23, P < 0.001). A study by Mease et al. indicated that patients receiving risankizumab generally demonstrated numerical improvements in the Leeds Enthesitis Index (LEI), although the small sample size limits the evidence. Further research is necessary to provide evidence-based guidelines. There were no significant differences in the incidence of serious adverse events (SAE) and serious treatment-emergent adverse events (STEAE) between the risankizumab and placebo groups (RR 0.76, 95% CI 0.45-1.28, P = 0.31; RR 0.99, 95% CI 0.49-1.99, P = 0.97, respectively), and the overall incidence of adverse events (AE) was not comparable (RR 1.10, 95% CI 0.63-1.94, P = 0.73). CONCLUSION: Risankizumab showed superior efficacy across multiple outcome measures compared to placebo, with no significant increase in adverse events. Our findings endorse risankizumab as an excellent treatment option for PsA, offering valuable insights for clinicians and patients when choosing appropriate therapeutic interventions. TRIAL REGISTRATION: Retrospectively registered (CRD42023451894, 16 August 2023).

miR828a-CsMYB114 Module Negatively Regulates the Biosynthesis of Theobromine in Camellia sinensis.

Theobromine is an important quality component in tea plants (Camellia sinensis), which is produced from 7-methylxanthine by theobromine synthase (CsTbS), the key rate-limiting enzyme in theobromine biosynthetic pathway. Our transcriptomics and widely targeted metabolomics analyses suggested that CsMYB114 acted as a potential hub gene involved in the regulation of theobromine biosynthesis. The inhibition of CsMYB114 expression using antisense oligonucleotides (ASO) led to a 70.21% reduction of theobromine level in leaves of the tea plant, which verified the involvement of CsMYB114 in theobromine biosynthesis. Furthermore, we found that CsMYB114 was located in the nucleus of the cells and showed the characteristic of a transcription factor. The dual luciferase analysis, a yeast one-hybrid assay, and an electrophoretic mobility shift assay (EMSA) showed that CsMYB114 activated the transcription of CsTbS, through binding to CsTbS promoter. In addition, a microRNA, miR828a, was identified that directly cleaved the mRNA of CsMYB114. Therefore, we conclude that CsMYB114, as a transcription factor of CsTbS, promotes the production of theobromine, which is inhibited by miR828a through cleaving the mRNA of CsMYB114.

Effect of male HBV infection on the outcomes of IVF/ICSI cycles: a retrospective cohort study based on propensity score matching.

ABSTRACT: This study aimed to investigate the effects of male hepatitis B virus (HBV) infection on male fertility, embryonic development, and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes. We performed a retrospective cohort study that included 3965 infertile couples who received fresh embryo transfer cycles for the first time at the Fujian Maternity and Child Health Hospital (Fuzhou, China) from January 2018 to January 2021. Infertile couples were categorized based on their HBV infection status into the HBV group (HBV-positive men and HBV-negative women) and the control group (HBV-negative couples). A 1:1 propensity score matching was performed with relatively balanced covariates. Baseline characteristics, semen parameters, laboratory outcomes, clinical outcomes, and obstetric and neonatal outcomes were compared between groups. After propensity score matching, 821 couples were included in each group. Both groups had similar semen parameters and obstetric and neonatal outcomes. The HBV group showed a significantly lower live birth rate than the control group (P < 0.05). The HBV group had a significantly higher abortion rate than the control group (P < 0.05). The rates of high-quality embryos and blastocyst formation were significantly lower in the HBV group than those in the control group (both P < 0.05). In conclusion, in couples who undergo IVF/ICSI, male HBV infection reduces the live birth rate and increases the risk of miscarriage. However, the incidence of low birth weight in women with IVF/ICSI does not increase with male HBV infection.

Improved gene therapy for spinal muscular atrophy in mice using codon-optimized hSMN1 transgene and hSMN1 gene-derived promotor.

Physiological regulation of transgene expression is a major challenge in gene therapy. Onasemnogene abeparvovec (Zolgensma®) is an approved adeno-associated virus (AAV) vector gene therapy for infants with spinal muscular atrophy (SMA), however, adverse events have been observed in both animals and patients following treatment. The construct contains a native human survival motor neuron 1 (hSMN1) transgene driven by a strong, cytomegalovirus enhancer/chicken ß-actin (CMVen/CB) promoter providing high, ubiquitous tissue expression of SMN. We developed a second-generation AAV9 gene therapy expressing a codon-optimized hSMN1 transgene driven by a promoter derived from the native hSMN1 gene. This vector restored SMN expression close to physiological levels in the central nervous system and major systemic organs of a severe SMA mouse model. In a head-to-head comparison between the second-generation vector and a benchmark vector, identical in design to onasemnogene abeparvovec, the 2nd-generation vector showed better safety and improved efficacy in SMA mouse model.

Research on the village layout optimization in China's developed areas based on daily life circles.

Public service facilities are the basic material carrier of social services. It is of great significance for the operation of social justice and the improvement of residents' wellbeing. In the process of rapid urbanization, the demand for traffic convenience and diversity of public service facilities in rural areas has been further improved. Since the sudden outbreak of the COVID-19 epidemic, it is more necessary to meet the public service needs of human daily life within a certain space. The huge gap between urban and rural infrastructures, human living conditions, and supporting public services such as education, health, and culture has become a key bottleneck constraining the integration of urban and rural areas. It is appropriate to focus on the requirements for the construction of daily life circles and prioritize the satisfaction of villagers' increasing demand for public services in regions characterized by high levels of urban-rural integration. The behavior preference of public service facilities significantly affects the choice of residential areas. The existing research on village layout optimization focused on the spatial pattern, landscape morphology, influencing factors, and other contents. To some extent, the preference for equalization of public services in the context of urban-rural integration has been ignored. Uneven distribution and low utilization of public service facilities in villages resulted in an inability to adapt spatially and functionally in response to the renewal of urban-rural relations. Taking a highly developed urban and rural integration area named Wuxi City of Jiangsu Province in China as an example, this paper combines the current situation of public service facility allocation and the transport situation of residents in rural areas to build a life-circle system of different levels. On this basis, combined with the optimization goal of public service facilities and the constraints of agglomeration coverage, we try to determine the village layout optimization scheme under the construction of both the daily life circle and location-allocation model. The study can effectively adjust the allocation of public resources in rural areas and solve the problems of irrational village layout leading to long travel distances. It can also serve as a reference for improving the situation of lagging rural public service functions and promoting urban-rural equalization.

Development and external validation of a nomogram for the early prediction of acute kidney injury in septic patients: a multicenter retrospective clinical study.

Background and purpose: Acute kidney injury (AKI) is a common serious complication in sepsis patients with a high mortality rate. This study aimed to develop and validate a predictive model for sepsis associated acute kidney injury (SA-AKI). Methods: In our study, we retrospectively constructed a development cohort comprising 733 septic patients admitted to eight Grade-A tertiary hospitals in Shanghai from January 2021 to October 2022. Additionally, we established an external validation cohort consisting of 336 septic patients admitted to our hospital from January 2017 to December 2019. Risk predictors were selected by LASSO regression, and a corresponding nomogram was constructed. We evaluated the model's discrimination, precision and clinical benefit through receiver operating characteristic (ROC) curves, calibration plots, decision curve analysis (DCA) and clinical impact curves (CIC) in both internal and external validation. Results: AKI incidence was 53.2% in the development cohort and 48.2% in the external validation cohort. The model included five independent indicators: chronic kidney disease stages 1 to 3, blood urea nitrogen, procalcitonin, D-dimer and creatine kinase isoenzyme. The AUC of the model in the development and validation cohorts was 0.914 (95% CI, 0.894-0.934) and 0.923 (95% CI, 0.895-0.952), respectively. The calibration plot, DCA, and CIC demonstrated the model's favorable clinical applicability. Conclusion: We developed and validated a robust nomogram model, which might identify patients at risk of SA-AKI and promising for clinical applications.

Efficacy, safety and the lymphocyte subsets changes of low-dose IL-2 in patients with systemic lupus erythematosus: A systematic review and meta-analysis.

INTRODUCTION: Existing therapies of systemic lupus erythematosus (SLE) are efficacious only in certain patients. Developing new treatment methods is urgent. This meta-analysis aimed to evaluate the efficacy and safety of low-dose IL-2 (LD-IL-2). METHODS: According to published data from PubMed, Web of Science, Embase, ClinicalTrials.gov, MEDLINE, MEDLINE, Web of Knowledge, Cochrane Library, and FDA.gov, eight trials were included. RESULTS: After the LD-IL-2 treatment, 54.8% of patients had distinct clinical remission. The SRI-4 response rates were 0.819 (95% confidence interval [CI]: 0.745-0.894), and the SELENA-SLEDAI scores were significantly decreased (SMD = -2.109, 95% CI: [-3.271, -0.947], p < .001). Besides, the proportions of CD4+ T (SMD = 0.614, 95% CI: [0.250, 0.979], p = .001) and Treg cells (SMD = 1.096, 95% CI: [0.544, 1.649], p < .001) were increased dramatically after LD-IL-2 treatment, while there were no statistical differences in the proportions of CD8+ T cells, Th1 cells, Th2 cells, and Th17 cells (p > .05). Besides, the proportions of Th17 (SMD = 1.121, 95% CI: [0.709, 1.533], p < .001) and Treg (SMD = 0.655, 95% CI: [0.273, 1.038], p = .001) were significantly increased after receiving subcutaneously 0.5 million IU of LD-IL-2 treatment per day for 5 days, but there were no statistical differences in the proportions of Treg after receiving 1 million IU every other day subcutaneously of LD-IL-2 treatment. Injection site reaction and fever were common side effects of IL-2, which occurred in 33.1% and 14.4% of patients. No serious adverse events were reported. CONCLUSION: LD-IL-2 was promising and well-tolerated in treating SLE, which could promote Treg's proliferation and functional recovery. Injecting 0.5 million IU of IL-2 daily can better induce the differentiation of Treg cells and maintain immune homeostasis than injecting 1 million IU every other day.

Response of salivary microbiome to temporal, environmental, and surface characteristics under in vitro exposure.

The microbiome of saliva stains deposited at crime scenes and in everyday settings is valuable for forensic investigations and environmental ecology. However, the dynamics and applications of microbial communities in these saliva stains have not been fully explored. In this study, we analyzed saliva samples that were exposed to indoor conditions for up to 1 year and to different carriers (cotton, sterile absorbent cotton swab, woolen, dacron) in both indoor and outdoor environments for 1 month using high-throughput sequencing. The analysis of microbial composition and Mfuzz clustering showed that the salivary flora, specifically Streptococcus (cluster7), which was associated with microbial contamination, remained stable over short periods of time. However, prolonged exposure led to significant differences due to the invasion of environmental bacteria such as Pseudomonas and Achromobacter. The growth and colonization of environmental flora were promoted by humidity. The neutral model predictions indicated that the assembly of salivary microbial communities in outdoor environments was significantly influenced by stochastic processes, with environmental characteristics having a greater impact on community change compared to surface characteristics. By incorporating data from previous studies on fecal and vaginal secretion microbiology, we developed RF and XGBoost classification models that achieved high accuracy (>98 %) and AUC (>0.8). Additionally, a RF regression model was created to determine the time since deposition (TsD) of the stains. Time inference models yielded a mean absolute error (MAE) of 7.1 days for stains exposed for 1 year and 14.2 h for stains exposed for 14 days. These findings enhance our understanding of the changes in the microbiome of saliva stains over time, in different environments, and on different surfaces. They also have potential applications in assessing potential microbial contamination, identifying body fluids, and inferring the time of deposition.

Natural lignocellulosic kapok fiber/MXene constructed hydrogel evaporators for high efficiency solar steam generation.

Solar-driven interfacial evaporation (SDIE) is a green and sustainable technique for desalination. Hydrogel composite evaporators have been widely used for SDIE, but it is still challenging for the hydrogel evaporators to achieve uniform distribution of the light absorbing nanomaterials and at the same time possess satisfactory evaporation rate, durability and environmental applicability. We developed a 3D hydrogel evaporator with an asymmetric structure for high-efficiency SDIE. Natural kapok fibers, an important lignocellulosic plant fiber with a hollow structure, are decorated with MXene nanosheets for construction of one-dimensional photothermal conversion network. The top composite hydrogel serves as the light-absorption layer where MXene-modified kapok fibers are evenly dispersed in PVA hydrogel, while the bottom PVA hydrogel with an oriented structure acts as water delivery path. The evaporator exhibits a high solar evaporation rate and efficiency (2.49 kg·m-2·h-1 and 91.5 %, respectively) under one sun irradiation (1 kW·m-2). Even in a high salinity brine, emulsion and corrosive solutions, the evaporator can work normally with a slightly decreased evaporation rate. The 3D hydrogel evaporator with long-term stability and durability shows promising applications in purification of seawater and different waste water.

Hepatocellular Ballooning is Due to Highly Pronounced Glycogenosis Potentially Associated with Steatosis and Metabolic Reprogramming.

Background and Aims: Hepatocellular ballooning is a common finding in chronic liver disease, mainly characterized by rarefied cytoplasm that often contains Mallory-Denk bodies (MDB). Ballooning has mostly been attributed to degeneration but its striking resemblance to glycogenotic/steatotic changes characterizing preneoplastic hepatocellular lesions in animal models and chronic human liver diseases prompts the question whether ballooned hepatocytes (BH) are damaged cells on the path to death or rather viable cells, possibly involved in neoplastic development. Methods: Using specimens from 96 cirrhotic human livers, BH characteristics were assessed for their glycogen/lipid stores, enzyme activities, and proto-oncogenic signaling cascades by enzyme- and immunohistochemical approaches with serial paraffin and cryostat sections. Results: BH were present in 43.8% of cirrhotic livers. Particularly pronounced excess glycogen storage of (glycogenosis) and/or lipids (steatosis) were characteristic, ground glass features and MDB were often observed. Decreased glucose-6-phosphatase, increased glucose-6-phosphate dehydrogenase activity and altered immunoreactivity of enzymes involved in glycolysis, lipid metabolism, and cholesterol biosynthesis were discovered. Furthermore, components of the insulin signaling cascade were upregulated along with insulin dependent glucose transporter glucose transporter 4 and the v-akt murine thymoma viral oncogene homolog/mammalian target of rapamycin signaling pathway associated with de novo lipogenesis. Conclusions: BH are hallmarked by particularly pronounced glycogenosis with facultative steatosis, many of their features being reminiscent of metabolic aberrations documented in preneoplastic hepatocellular lesions in experimental animals and chronic human liver diseases. Hence, BH are not damaged entities facing death but rather viable cells featuring metabolic reprogramming, indicative of a preneoplastic nature.

The antennal transcriptome analysis and characterizations of odorant-binding proteins in Megachile saussurei (Hymenoptera, Megachilidae).

BACKGROUND: Odorant-binding proteins (OBPs) are essential in insect's daily behaviors mediated by olfactory perception. Megachile saussurei Radoszkowski (Hymenoptera, Megachilidae) is a principal insect pollinating alfalfa (Medicago sativa) in Northwestern China. The olfactory function have been less conducted, which provides a lot of possibilities for our research. RESULTS: Our results showed that 20 OBPs were identified in total. Multiple sequence alignment analysis indicated MsauOBPs were highly conserved with a 6-cysteine motif pattern and all belonged to the classic subfamily, coding 113-196 amino acids and sharing 41.32%-99.12% amino acid identity with known OBPs of other bees. Phylogenetic analysis indicated there were certain homologies existed among MsauOBPs and most sequences were clustered with that of Osmia cornuta (Hymenoptera, Megachilidae). Expression analysis showed the identified OBPs were mostly enriched in antennae instead of other four body parts, especially the MsauOBP2, MsauOBP3, MsauOBP4, MsauOBP8, MsauOBP11 and MsauOBP17, in which the MsauOBP2, MsauOBP4 and MsauOBP8 presented obvious tissue-biased expression pattern. Molecular docking results indicated MsauOBP4 might be the most significant protein in recognizing alfalfa flower volatile 3-Octanone, while MsauOBP13 might be the most crucial protein identifying (Z)-3-hexenyl acetate. It was also found the lysine was a momentous hydrophilic amino acid in docking simulations. CONCLUSION: In this study, we identified and analyzed 20 OBPs of M. saussurei. The certain homology existed among these OBPs, while some degree of divergence could also be noticed, indicating the complex functions that different MsauOBPs performed. Besides, the M. saussurei and Osmia cornuta were very likely to share similar physiological functions as most of their OBPs were clustered together. MsauOBP4 might be the key protein in recognizing 3-Octanone, while MsauOBP13 might be the key protein in binding (Z)-3-hexenyl acetate. These two proteins might contribute to the alfalfa-locating during the pollination process. The relevant results may help determine the highly specific and effective attractants for M. saussurei in alfalfa pollination and reveal the molecular mechanism of odor-evoked pollinating behavior between these two species.

Real-world tobacco cessation practice in China: findings from the prospective, nationwide multicenter China National Tobacco Cessation Cohort Study (CNTCCS).

Background: Tobacco cessation is proven to be the most effective and cost-effective strategy for smokers to reduce their risk of smoking-related disease and premature death. Providing effective, efficient, safe, and patient-centred tobacco cessation treatment to reach those who need them is a significant challenge. To date, only a few nationwide studies in China have assessed the overall clinical care practice and treatment outcome of tobacco cessation. Methods: This a prospective, nationwide, multicenter, cohort study covering all Eastern China, Northwest China, Central China, North China, Southwest China, Northeast China, and South China. Participants who were current smokers aged 18-85 years attending clinic for smoking cessation were included. All the participants were treated with 3-month cessation treatment and followed up for 3 months. Data were collected prospectively using online system. The primary outcome was 7-day point abstinence rate at 24 weeks, validated biochemically by an expired carbon monoxide level of less than 10 ppm. The participants lost to follow-up or not providing validation were included as non-abstainers. Findings: A representative sample of 3557 participants were recruited and 2943 participants were included into this analysis. These participants had mean age of 53.05 years, and 94.8% were males, with 75.8% showing symptoms of tobacco dependence. A total of 965 (32.8%) participants were treated with Bupropion + behavioural counselling, followed by 935 (31.8%) with behavioural counselling, 778 (26.4%) with Varenicline + behavioural counselling, 135 (4.6%) with alternative treatments + behavioural counselling, and 130 (4.4%) with nicotine replacement therapy (NRT) + behavioural counselling. After 3-month treatment and 3-month follow-up, 21.74% of the participants quit smoking at 24 weeks. In the multivariable-adjusted analyses, quitting smoking was significantly associated with female, higher socioeconomic status, poor health condition, different treatment received, and less smoking intensity. The tobacco cessation treatment varied widely across different areas of China. In particular, the areas with higher usage of cessation medication were associated with better cessation treatment outcome. Interpretation: The CNTCCS is the first large-scale nationwide cohort study of smoking cessation in China. Rich data collected from this prospective cohort study provided the opportunity to evaluate the clinical practice of tobacco cessation treatment in China. Funding: Chinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine (CAMS 2021-I2M-1-010), Heilongjiang Provincial Science and Technology Key Program (2022ZXJ03C02), and National Key R&D Program of China (grant no. 2017YFC1309400).