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Abstract This paper introduces an adaptive control scheme for quadrotor suspended load systems, to track desired trajectory with variable payload and wind disturbances. The dynamic model of the quadrotor suspended load system is developed, taking into account the impact of the wind field described by the Dryden model. To attenuate the effects of payload variation and wind disturbances on the system, an adaptive control method based on disturbance observers is devised. Additionally, the uniform boundedness of all error signals is demonstrated. The effectiveness of the designed control method is verified through simulations, which serves to strengthen its applicability in practical applications.

Background: Sivelestat, a neutrophil elastase inhibitor, is postulated to mitigate acute lung injury in patients following emergency surgery. However, its efficacy in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) induced by coronavirus disease 2019 (COVID-19) remains uncertain. This study aims to evaluate the pulmonary protective effects of sivelestat in COVID-19 patients with ALI/ARDS. Methods: A retrospective study was conducted involving 2454 COVID-19 patients between October 5, 2022, and February 1, 2023. Of these, 102 patients received sivelestat (0.2 mg/kg/h), while 2352 age- and sex-matched controls were identified. Propensity score matching (PSM) analysis was used to match sivelestat and non-sivelestat subgroups in ratios of 1:1 and 1:3 for sensitivity analysis. The primary outcome was a composite of effective outcomes, including 30-day mortality. Secondary outcomes included changes in partial pressure of arterial oxygen (PaO2), the ratio of PaO2 to the fraction of inspired oxygen (PaO2/FiO2), and various cytokine levels. Safety evaluations included assessments of liver function, kidney function, and leukopenia. Results: In the propensity score-matched analysis, the sivelestat group had a higher proportion of severe/critical patients (87.26 % vs. 51.02 %, P

ABSTRACT The global burden of infections due to the pathogenic fungus Cryptococcus is substantial in persons with low CD4+ T-cell counts. Previously, we deleted three chitin deacetylase genes from Cryptococcus neoformans to create a chitosan-deficient, avirulent strain, designated as cda1∆2∆3∆, which, when used as a vaccine, protected mice from challenge with virulent C. neoformans strain KN99. Here, we explored the immunological basis for protection. Vaccine-mediated protection was maintained in mice lacking B cells or CD8+ T cells. In contrast, protection was lost in mice lacking α/β T cells or CD4+ T cells. Moreover, CD4+ T cells from vaccinated mice conferred protection upon adoptive transfer to naive mice. Importantly, while monoclonal antibody-mediated depletion of CD4+ T cells just prior to vaccination resulted in complete loss of protection, significant protection was retained in mice depleted of CD4+ T cells after vaccination but prior to challenge. Vaccine-mediated protection was lost in mice genetically deficient in interferon-γ (IFNγ), tumor necrosis factor alpha (TNFα), or interleukin (IL)-23p19. A robust influx of leukocytes and IFNγ- and TNFα-expressing CD4+ T cells was seen in the lungs of vaccinated and challenged mice. Finally, a higher level of IFNγ production by lung cells stimulated ex vivo correlated with lower fungal burden in the lungs. Thus, while B cells and CD8+ T cells are dispensable, IFNγ and CD4+ T cells have overlapping roles in generating protective immunity prior to cda1∆2∆3∆ vaccination. However, once vaccinated, protection becomes less dependent on CD4+ T cells, suggesting a strategy for vaccinating HIV+ persons prior to loss of CD4+ T cells.IMPORTANCEThe fungus Cryptococcus neoformans is responsible for >100,000 deaths annually, mostly in persons with impaired CD4+ T-cell function such as AIDS. There are no approved human vaccines. We previously created a genetically engineered avirulent strain of C. neoformans, designated as cda1∆2∆3∆. When used as a vaccine, cda1∆2∆3∆ protects mice against a subsequent challenge with a virulent C. neoformans strain. Here, we defined components of the immune system responsible for vaccine-mediated protection. We found that while B cells and CD8+ T cells were dispensible, protection was lost in mice genetically deficient in CD4+ T cells and the cytokines IFNγ, TNFα, or IL-23. A robust influx of cytokine-producing CD4+ T cells was seen in the lungs of vaccinated mice following infection. Importantly, protection was retained in mice depleted of CD4+ T cells following vaccination, suggesting a strategy to protect persons who are at risk of future CD4+ T-cell dysfunction.

The fungal infection, cryptococcosis, is responsible for >100,000 deaths annually. No licensed vaccines are available. We explored the efficacy and immune responses of subunit cryptococcal vaccines adjuvanted with Cationic Adjuvant Formulation 01 (CAF01). CAF01 promotes humoral and T helper (Th) 1 and Th17 immune responses and has been safely used in human vaccine trials. Four subcutaneous vaccines, each containing single recombinant Cryptococcus neoformans protein antigens, partially protected mice from experimental cryptococcosis. Protection increased, up to 100%, in mice that received bivalent and quadrivalent vaccine formulations. Vaccinated mice that received a pulmonary challenge with C. neoformans had an influx of leukocytes into the lung including robust numbers of polyfunctional CD4+ T cells which produced interferon gamma (IFNγ), tumor necrosis factor alpha (TNFα), and interleukin (IL)-17 upon ex vivo antigenic stimulation. Cytokine-producing lung CD8+ T cells were also found, albeit in lesser numbers. A significant, durable IFNγ response was observed in the lungs, spleen, and blood. Moreover, IFNγ secretion following ex vivo stimulation directly correlated with fungal control in the lungs. Thus, we have developed multivalent cryptococcal vaccines which protect mice from experimental cryptococcosis using an adjuvant which has been safely tested in humans. These preclinical studies suggest a path towards human cryptococcal vaccine trials.

Introduction and Objectives: Type 2 Diabetes Mellitus (T2DM), a prevalent metabolic disorder, often coexists with a range of complications, with retinopathy being particularly common. Recent studies have shed light on a potential connection between diabetic retinopathy (DR) and hepatic fibrosis, indicating a possible shared pathophysiological foundation in T2DM. This study investigates the correlation between retinopathy and hepatic fibrosis among individuals with T2DM, as well as evaluates the diagnostic value of DR for significant hepatic fibrosis. Materials and Methods: Our cross-sectional analysis incorporated 5413 participants from the National Health and Nutrition Examination Survey (NHANES) 2005-2008. The Fibrosis-4 score (FIB-4) classified hepatic fibrosis into different grades (F0-F4), with significant hepatic fibrosis marked as F2 or higher. Retinopathy severity was determined using retinal imaging and categorized into four levels. The analysis of variance or Chi-square tests facilitated group comparisons. Additionally, the receiver operating characteristic (ROC) analysis appraised the predictive accuracy of retinopathy for significant hepatic fibrosis in the T2DM population. Results: Among 5413 participants, the mean age was 59.56 ± 12.41, with 50.2% male. And 20.6% were diagnosed with T2DM. Hepatic fibrosis grading was positively associated with retinopathy severity (OR [odds ratio]: 1.521, 95%CI [confidence interval]: 1.152-2.008, P = 0.003) across the entire population. The association was amplified in the T2DM population according to Pearson's analysis results. The ROC curve demonstrated retinopathy's diagnostic capacity for significant hepatic fibrosis in the T2DM population (AUC [area under curve] = 0.72, 95%CI: 0.651-0.793, P < 0.001). Conclusions: Retinopathy could serve as an independent predictor of significant hepatic fibrosis in T2DM population. Ophthalmologists are advised to closely monitor T2DM patients with retinopathy.

Abstract We aimed to identify the key potential insulin resistance (IR)-related genes and investigate their correlation with immune cell infiltration in type 2 diabetes (T2D). The GSE78721 dataset (68 diabetic patients and 62 controls) was downloaded from the Gene Expression Omnibus database and utilized for single-sample gene set enrichment analysis. IR-related genes were obtained from the Comparative Toxicology Genetics Database, and the final IR-differentially expressed genes (DEGs) were screened by intersecting with the DEGs obtained from the GSE78721 datasets. Functional enrichment analysis was performed, and the networks of the target gene with microRNA, transcription factor, and drug were constructed. Hub genes were identified based on a protein–protein interaction network. Least absolute shrinkage and selection operator regression and Random Forest and Boruta analysis were combined to screen diagnostic biomarkers in T2D, which were validated using the GSE76894 (19 diabetic patients and 84 controls) and GSE9006 (12 diabetic patients and 24 controls) datasets. Quantitative real-time polymerase chain reaction was performed to validate the biomarker expression in IR mice and control mice. In addition, infiltration of immune cells in T2D and their correlation with the identified markers were computed using CIBERSORT. We identified differential immune gene set regulatory T-cells in the GSE78721 dataset, and T2D samples were assigned into three clusters based on immune infiltration. A total of 2094 IR-DEGs were primarily enriched in response to endoplasmic reticulum stress. Importantly, HDAC9 and ARRDC4 were identified as markers of T2D and associated with different levels of immune cell infiltration. HDAC9 mRNA level were higher in the IR mice than in control mice, while ARRDC4 showed the opposite trend. In summary, we discovered potential vital biomarkers that contribute to immune cell infiltration associated with IR, which offers a new sight of immunotherapy for T2D.

Abstract Background Nutritional deficiencies remain serious medical and public health issues worldwide, especially in children. This study aims to analyze cross-country inequality in four common nutritional deficiencies (protein-energy malnutrition, dietary iron deficiency, vitamin A deficiency and iodine deficiency) among children from 1990 to 2019 based on Global Burden of Disease (GBD) 2019 data. Methods Prevalence and disability-adjusted life years (DALYs) data as measures of four nutritional deficiency burdens in people aged 0 to 14 years were extracted from the GBD Results Tool. We analyzed temporal trends in prevalence by calculating the average annual percent change (AAPC) and quantified cross-country inequalities in disease burden using the slope index. Results Globally, the age-standardized prevalence rates of dietary iron deficiency, vitamin A deficiency and iodine deficiency decreased, with AAPCs of -0.14 (-0.15 to -0.12), -2.77 (-2.96 to -2.58), and -2.17 (-2.3 to -2.03) from 1999 to 2019, respectively. Significant reductions in socio-demographic index (SDI)-related inequality occurred in protein-energy malnutrition and vitamin A deficiency, while the health inequality for dietary iron deficiency and iodine deficiency remained basically unchanged. The age-standardized prevalence and DALY rates of the four nutritional deficiencies decreased as the SDI and healthcare access and quality index increased. Conclusions The global burden of nutritional deficiency has decreased since 1990, but cross-country health inequalities still exist. More efficient public health measures are needed to reduce disease burdens, particularly in low-SDI countries/territories.

Objectives This study focuses on the sealing performance of lifting hatches applied to nuclear power plants under accidental working conditions.MethodsAn experimental setup is built to achieve the quantitative measurement of steam micro-leakage. In this device, saturated steam at 0.66 MPa is charged into a pressurized chamber to simulate accident conditions, the leaking steam is collected through a collection chamber with an insulation layer, and no condensation occurs. The changes in temperature, humidity and pressure in the collection chamber are monitored in real time to estimate the steam leakage rate.ResultsThe experimental results show that the steam leakage rates of the lifting hatch models with 1.5 mm and 3.0 mm composite gaskets are 13.93 g/24h and 11.91 g/24h respectively, both meeting the low leakage design requirements, with the 3.0 mm gasket providing superior sealing performance. An analysis of the dry air and steam measurements with the same gasket and at the same pressure shows that the sealing coefficients nd4 obtained for both are very close, which verifies the accuracy of the experimental device for steam microleakage measurements.ConclusionsThe proposed steam microleakage measurement method can be extended to various sealing structures and pressure systems, and provides a new measurement idea for evaluating the sealability of stack chambers under accident conditions.

Abstract Background The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and its subsequent Omicron variant has raised concerns for chronic obstructive pulmonary disease (COPD) patients due to the potential risk of disruptions to healthcare services and unknown comorbidities between COPD and Omicron. Method In this study, we conducted a follow‐up investigation of 315 COPD patients during the Omicron outbreak at Shanxi Bethune Hospital to understand the impact of the pandemic on this vulnerable population. Among all patients, 228 were infected with Omicron, of which 82 needed hospitalizations. Result We found that COPD patients with high blood eosinophil (EOS) counts exhibited lower susceptibility to Omicron infection and were more likely to have milder symptoms that did not require hospitalization. Conversely, patients with low EOS counts showed higher rates of infection and hospitalization. Moreover, EOS count was positively correlated with T lymphocyte counts in hospitalized patients after Omicron infection, suggesting potential associations between EOS and specific immune responses in COPD patients during viral infections. Correlation analysis revealed a positive correlation between EOS count and lymphocyte and T‐cells, and a negative correlation between EOS count and age, neutrophil, and C‐reactive protein. Conclusion Overall, our study contributes to the knowledge of COPD management during the COVID‐19 Omicron outbreak and emphasizes the importance of considering individual immune profiles to improve care for COPD patients in the face of the ongoing global health crisis.

In spite of the increasing popularity of project-based collaborative learning (PBCL) as a pedagogy, real successful collaboration cannot always be achieved due to the cognitive, motivational and social emotional challenges students encounter during collaboration. Recognizing the challenges and developing regulation strategies to cope with the challenges at both individual and group level is essential for successful collaboration. In the last decades, a growing interest has been developed around socially shared regulation of emotions and how it is interwoven with self-regulation and co-regulation. However, capturing the process of students’ emotional challenges and regulations in a long and dynamic project proves difficult and there remains a paucity of evidence on how co-regulation and socially-shared regulation co-occur with learners’ cognitive and emotional progress in project-based collaborative learning. The purpose of the present study is to investigate and identify what kind of social emotional challenges students encountered during PBCL and how they regulate themselves and the groups in order to finish the projects. A quasi-experimental research design was adopted in an academic English classroom, with thirty-eight students self-reporting their challenges and regulations three times after finishing each of the projects. The results of qualitative analysis plus a case study of two groups indicate that students encounter a variety of social emotional challenges and employed different levels of co-regulation and socially shared regulation in addition to self-regulation, leading to varying collaboration results and experiences. The findings of the study offer insights into the emotional regulation in PBCL and shed light for future design of pedagogical interventions aiming at supporting socially shared regulation.

Streptococcus agalactiae (S.agalactiae), also known as group B Streptococcus (GBS), is a highly infectious pathogen. Prolonged antibiotic usage leads to significant issues of antibiotic residue and resistance. Chelerythrine (CHE) is a naturally occurring benzophenidine alkaloid and chelerythrine chloride (CHEC) is its hydrochloride form with diverse biological and pharmacological activities. However, the antibacterial mechanism of CHEC against GBS remains unclear. Thus, this study aims to investigate the in vitro antibacterial activity of CHEC on GBS and elucidate its underlying mechanism. The antibacterial effect of CHEC on GBS was assessed using inhibitory zone, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) assays, as well as by constructing a time-kill curve. The antibacterial mechanism of CHEC was investigated through techniques such as scanning electron microscopy (SEM) and transmission electron microscopy (TEM), measurement of alkaline phosphatase (AKP) activity, determination of Na+ K+, Ca2+ Mg2+—adenosine triphosphate (ATP) activity, observation of membrane permeability, and analysis of intracellular reactive oxygen species (ROS) and mRNA expression levels of key virulence genes. The results demonstrated that the inhibition zone diameters of CHEC against GBS were 14.32 mm, 12.67 mm, and 10.76 mm at concentrations of 2 mg/mL, 1 mg/mL, and 0.5 mg/mL, respectively. The MIC and MBC values were determined as 256 μg/mL and 512 μg/mL correspondingly. In the time-kill curve, 8 × MIC, 4 × MIC and 2 × MIC CHEC could completely kill GBS within 24 h. SEM and TEM analyses revealed significant morphological alterations in GBS cells treated with CHEC including shrinkage, collapse, and leakage of cellular fluids. Furthermore, the antibacterial mechanism underlying CHEC’s efficacy against GBS was attributed to its disruption of cell wall integrity as well as membrane permeability resulting in extracellular release of intracellular ATP, AKP, Na+ K+, Ca2+ Mg2+. Additionally CHEC could increase the ROS production leading to oxidative damage and downregulating mRNA expression levels of key virulence genes in GBS cells. In conclusion, CHEC holds potential as an antimicrobial agent against GBS and further investigations are necessary to elucidate additional molecular mechanisms.

In recent years, it is not uncommon for swelling soil landslides to occur again after treatment, which has seriously affected the safe operation of highways and railways. The degree of consolidation and cementation of swelling soil is poor, and its fractures are developed and it has a certain expansibility. Under the action of expansion force, its shear strength is obviously reduced. Thus, anti-slide pile support is used to control swelling soil landslides in this study. Based on the geological conditions and genetic mechanism of swelling soil landslide, a three-dimensional geological model with a width of 40 m is established to simulate the interaction mechanism and influencing factors between soil and pile in the process of anti-slip pile support. The results show that the larger the cohesion and internal friction angle, the stronger the soil arch effect, but the sensitivity is higher when the value is small. Therefore, attention should be paid to the weakening effect of soil arch effect in soil with low shear strength. The larger the pile spacing, the less obvious the soil arch effect. The swelling force also has a great influence on the soil arch effect from scratch. With the increase of the expansive force, the soil arch effect is weakened and completely disappears. Therefore, the adverse effects of expansive force should be considered, when designing anti-slide piles in swelling soil areas.

As a representative item of chemical carcinogen, MNNG is closely associated with the onset of gastric cancer (GC), where N6-methyladonosine (m6A) RNA methylation is recognized as a critical epigenetic event. In our previous study, we found that the m6A modification by methyltransferase METTL3 was up-regulated in MNNG-exposed malignant GES-1 cells (MC cells) compared to control cells in vitro, and long non-coding RNA SNHG7 as a downstream target of the METTL3. However, the functional role of METTL3 in mediating the SNHG7 axis in MNNG-induced GC remains unclear. In the present study, we continuously investigate the functional role of METTL3 in mediating the SNHG7 axis in MNNG-induced GC. RIP-PCR and m6A-IP-qPCR were used to examine the molecular mechanism underlying the METTL3/m6A/SNHG7 axis in MNNG-induced GC. A METTL3 knockout mice model was constructed and exposed by MNNG. Western blot analysis, IHC analysis, and RT-qPCR were used to measure the expression of METTL3, SNHG7, and EMT markers. In this study, we demonstrated that in MNNG-induced GC tumorigenesis, the m6A modification regulator METTL3 facilitates cellular EMT and biological functions through the m6A/SNHG7 axis using in vitro and in vivo models. In conclusion, our study provides novel insights into critical epigenetic molecular events vital to MNNG-induced gastric carcinogenesis. These findings suggest the potential therapeutic targets of METTL3 for GC treatment.

Mucosal immunity is the main defense line against respiratory disease pathogens. Newcastle disease and avian infectious bronchitis are common respiratory diseases in poultry. However, the mucosal immune response is not sufficiently activated and thus fails to achieve the ideal immune protection. Therefore, it is important to develop a suitable mucosal immune adjuvant to enhance the immune response of live vaccines. Here, the bursal-derived peptide BP7, β-glucan, and hyaluronic acid were selected as the adjuvant to be assembled into the composite nanopolypeptide adjuvant (CNPB7) with ultrasonic dispersion technology. The results showed that after optimizing assembly conditions, the optimal average particle size of nanoparticle CNPB7 was 514.9 nm and PDI was 0.298. To evaluate the non-specific immune responses of nanoparticle CNPB7, the chickens were immunized only with nanoparticle CNPB7. It was confirmed that nanoparticle CNPB7 enhanced the expression of CD3, CD4, CD80, and CD86 factors in the spleen lymphocyte from the chicken immunized with nanoparticle CNPB7. To investigate the mucosal immune response of nanoparticle CNPB7, the chickens were orally immunized with Newcastle disease virus (NDV)–infectious bronchitis virus (IBV) dual vaccines and CNPB7. The results proved that the levels of immunoglobulin SIgA, IL-4, IFN-γ, and IL-13 in the mucus samples from the respiratory and digestive tract in chicken immunized with nanoparticle CNPB7 and vaccines were significantly increased, compared to that of vaccine control. Finally, it was observed that nanoparticle CNPB7 promoted specific increased antibody productions against NDV and IBV in the immunized chicken. These results proved that the assembled nanoparticle CNPB7 could enhance the vaccination efficacy in chicken, which provided the experimental basis for the development of new adjuvants, and offered technical support for preventing virus transmission of avian diseases.

BackgroundMaternal smoking during pregnancy (MSDP) is a known risk factor for offspring developing chronic obstructive pulmonary disease (COPD), but the underlying mechanism remains unclear. ObjectiveThis study aimed to explore whether the increased COPD risk associated with MSDP could be attributed to tobacco dependence (TD). MethodsThis case-control study used data from the nationwide cross-sectional China Pulmonary Health study, with controls matched for age, sex, and smoking status. TD was defined as smoking within 30 minutes of waking, and the severity of TD was assessed using the Fagerstrom Test for Nicotine Dependence. COPD was diagnosed when the ratio of forced expiratory volume in 1 second to forced vital capacity was

Abstract Background The fracture risk of patients with chronic obstructive pulmonary disease (COPD) treated with inhaled corticosteroids is controversial. And some large-scale randomized controlled trials have not solved this problem. The purpose of our systematic review and meta-analysis including 44 RCTs is to reveal the effect of inhaled corticosteroids on the fracture risk of COPD patients. Methods Two reviewers independently retrieved randomized controlled trials of inhaled corticosteroids or combinations of inhaled corticosteroids in the treatment of COPD from PubMed, Embase, Medline, Cochrane Library, and Web of Science. The primary outcome was a fracture event. This study was registered at PROSPERO (CRD42022366778). Results Forty-four RCTs were performed in 87,594 patients. Inhaled therapy containing ICSs (RR, 1.19; 95%CI, 1.04–1.37; P = 0.010), especially ICS/LABA (RR, 1.30; 95%CI, 1.10–1.53; P = 0.002) and triple therapy (RR, 1.49; 95%CI, 1.03–2.17; P = 0.04) were significantly associated with the increased risk of fracture in COPD patients when compared with inhaled therapy without ICSs. Subgroup analyses showed that treatment duration ≥ 12 months (RR, 1.19; 95%CI, 1.04–1.38; P = 0.01), budesonide therapy (RR, 1.64; 95%CI., 1.07–2.51; P = 0.02), fluticasone furoate therapy (RR, 1.37; 95%CI, 1.05–1.78; P = 0.02), mean age of study participants ≥ 65 (RR, 1.27; 95%CI, 1.01–1.61; P = 0.04), and GOLD stage III(RR, 1.18; 95%CI, 1.00–1.38; P = 0.04) were significantly associated with an increased risk of fracture. In addition, budesonide ≥ 320 ug bid via MDI (RR, 1.75; 95%CI, 1.07–2.87; P = 0.03) was significantly associated with the increased risk of fracture. Conclusion Inhalation therapy with ICSs, especially ICS/LABA or triple therapy, increased the risk of fracture in patients with COPD compared with inhaled therapy without ICS. Treatment duration, mean age of participants, GOLD stage, drug dosage form, and drug dose participated in this association. Moreover, different inhalation devices of the same drug also had differences in risk of fracture.

Quadrotors are widely applied in many fields, but they often face various external disturbances in actual operation. This makes it necessary to design a controller that can handle disturbances. Disturbance observer and adaptive control techniques are commonly used disturbance rejection techniques, the core idea of which is to estimate the disturbances in real time and incorporate the estimated values into the controller to suppress the disturbances. In this paper, various disturbance observers and adaptive control techniques, including nonlinear disturbance observers, extended state observers, neural networks, and fuzzy logic systems, are introduced, along with their variants or different structures. These techniques improve the adaptability and robustness of quadrotors to complex environments. Finally, future research directions for the disturbance rejection of quadrotors are also presented.

A novel non-isothermal glass hot embossing system utilizes a silicon mold core coated with a three-dimensional carbide-bonded graphene (CBG) coating, which acts as a thin-film resistance heater. The temperature of the system significantly influences the electrical conductivity properties of silicon with a CBG coating. Through simulations and experiments, it has been established that the electrical conductivity of silicon with a CBG coating gradually increases at lower temperatures and rapidly rises as the temperature further increases. The CBG coating predominantly affects electrical conductivity until 400 °C, after which silicon becomes the dominant factor. Furthermore, the dimensions of CBG-coated silicon and the reduction of CBG coating also affect the rate and outcome of conductivity changes. These findings provide valuable insights for detecting CBG-coated silicon during the embossing process, improving efficiency, and predicting the mold core’s service life, thus enhancing the accuracy of optical lens production.

Abstract Background The associations between short- and long-term exposure to ambient fine particulate matter with an aerodynamic diameter ≤ 2.5 µm (PM2.5) and allergic symptoms in middle-aged and elderly populations remain unclear, particularly in China, where most cities have severe air pollution. Methods Participants (n = 10,142; age = 40–75 years) were recruited from ten regions in China from 2018 to 2021 for the Predictive Value of Inflammatory Biomarkers and Forced Expiratory Volume in 1 s (FEV1) for Chronic Obstructive Pulmonary Disease (PIFCOPD) study. Short-term (lag0 and lag0–7 day) and long-term (1-, 3- and 5-year) PM2.5 concentrations at residences were extracted from the air pollutant database known as Tracking Air Pollution (TAP) in China. Multivariate logistic regression models were used to estimate associations for short- and long-term PM2.5 exposure concentrations and long-term exposure models were additionally adjusted for short-term deviations. Results A 10 µg/m3 increase in PM2.5 on the day the allergic symptoms questionnaire was administered (lag0 day) was associated with higher odds of allergic nasal (1.09, 95% CI 1.05, 1.12) and eye symptoms (1.08, 95% CI 1.05, 1.11), worsening dyspnea caused by allergens (1.06, 95% CI 1.02, 1.10), and ≥ 2 allergic symptoms (1.07, 95% CI 1.03, 1.11), which was similar in the lag0–7 day concentrations. A 10 µg/m3 increase in the 1-year average PM2.5 concentration was associated with an increase of 23% for allergic nasal symptoms, 22% for eye symptoms, 20% for worsening dyspnea caused by allergens, and 21% for ≥ 2 allergic symptoms, similar to the 3- and 5-year average PM2.5 concentrations. These associations between long-term PM2.5 concentration and allergic symptoms were generally unchanged after adjustment for short-term deviations. Conclusions Short- and long-term exposure to ambient PM2.5 was associated with an increased risk of allergic nasal and eye symptoms, worsening dyspnea caused by allergens, and ≥ 2 allergic symptoms. Trial registration Clinical trial ID: NCT03532893 (29 Mar 2018).

ABSTRACT Multidrug-resistant (MDR) Pseudomonas aeruginosa infections pose a significant challenge to effective treatment. Although carbapenems were once considered the primary therapeutic option for MDR P. aeruginosa, the clinical use of these antibiotics has become increasingly limited, and the exploration of alternative antimicrobial strategies remains necessary. Bacterial surface glycans are critical in response to antibiotics and represent an attractive therapeutic target. However, the understanding of the role of glycan structures in bacterial resistance is currently quite limited. In this study, we used lectin microarrays to analyze the differences in glycan alterations between 53 drug-sensitive P. aeruginosa (DSPA) strains and 57 carbapenem-resistant P. aeruginosa (CRPA) strains obtained from clinical isolates, with the goal of identifying important glycopatterns associated with carbapenem resistance. The results revealed significant differences in the expression levels of glycan structures [e.g., Fucα1–6GlcNAc, α-d-Man, and Fucα1–3(Galβ1–4)GlcNAc] recognized by 20 lectins (e.g., LCA, PSA, and AAL) on the bacterial surface. Furthermore, we applied K-fold cross-validation to determine the optimal parameters and constructed the DSPA and CRPA models using gradient boosting decision tree (GBDT) algorithm. The GBDT model presented the best performance in an independent test cohort, demonstrating that the screened glycopatterns could serve as potential biomarkers for differentiating bacterial resistance. Our study is the first to apply lectin microarrays to monitor carbapenem resistance in clinical P. aeruginosa isolates, and we hope that the methodology used in this work will serve as an important tool for exploring the association of bacterial resistance with glycosylation mechanisms. IMPORTANCE Bacterial surface glycans are an attractive therapeutic target in response to antibiotics; however, current knowledge of the corresponding mechanisms is rather limited. Antimicrobial susceptibility testing, genome sequencing, and MALDI-TOF MS, commonly used in recent years to analyze bacterial resistance, are unable to rapidly and efficiently establish associations between glycans and resistance. The discovery of new antimicrobial strategies still requires the introduction of promising analytical methods. In this study, we applied lectin microarray technology and a machine-learning model to screen for important glycan structures associated with carbapenem-resistant P. aeruginosa. This work highlights that specific glycopatterns can be important biomarkers associated with bacterial antibiotic resistance, which promises to provide a rapid entry point for exploring new resistance mechanisms in pathogens.

Abstract Lipopolysaccharide (LPS) displays a robust immunostimulatory ability upon Toll-like receptor 4 (TLR4) recognition. N-methyl-D-aspartate receptors (NMDARs) are highly compartmentalized in most cells and implicated in various inflammatory disorders. However, the relationship between TLR4 and NMDARs has not been explored deeply. This study aimed to examine the role of NMDARs and its specific inhibitor MK801 in LPS-treated endothelial cell dysfunction and the related mechanism in vivo and in vitro. The results showed that pre-treatment with MK801 significantly decreased LPS-induced cell death, cellular Ca2+, cellular reactive oxygen species, and glutamate efflux. Moreover, MK801 restrained LPS-induced mitochondrial dysfunction by regulating mitochondrial membrane potential and mitochondrial Ca2+ uptake. The oxygen consumption, basal and maximal respiration rate, and ATP production in LPS-treated HUVECs were reversed by MK801 via regulating ATP synthesis-related protein SDHB2, MTCO1, and ATP5A. The molecular pathway involved in MK801-regulated LPS injury was mediated by phosphorylation of CaMKII and ERK and the expression of MCU, MCUR1, and TLR4. LPS-decreased permeability in HUVECs was improved by MK801 via the Erk/ZO-1/occluding/Cx43 axis. Co-immunoprecipitation assay and western blotting showed three subtypes of NMDARs, NMDAζ1, NMDAε2, and NMDAε4 were bound explicitly to TLR4, suppressed by LPS, and promoted by MK801. Deficiency of NMDAζ1, NMDAε2, or NMDAε4 induced cell apoptosis, Ca2+ uptake, ROS production, and decreased basal and maximal respiration rate, and ATP production, suggesting that NMDARs integrity is vital for cell and mitochondrial function. In vivo investigation showed MK801 improved impairment of vascular permeability, especially in the lung and mesentery in LPS-injured mice. Our study displayed a novel mechanism and utilization of MK801 in LPS-induced ECs injury and permeability.

Abstract Vaccination with glucan particles (GP) containing the Cryptococcus neoformans chitin deacetylases Cda1 and Cda2 protect mice against experimental cryptococcosis. Here, immunological correlates of vaccine-mediated protection were explored. Studies comparing knockout and wild-type mice demonstrated CD4+ T cells are crucial, while B cells and CD8+ T cells are dispensable. Protection was abolished following CD4+ T cell depletion during either vaccination or infection but was retained if CD4+ T cells were only partially depleted. Vaccination elicited systemic and durable antigen-specific immune responses in peripheral blood mononuclear cells (PBMCs), spleens, and lungs. Following vaccination and fungal challenge, robust T-helper (Th) 1 and Th17 responses were observed in the lungs. Protection was abrogated in mice congenitally deficient in interferon (IFN) γ, IFNγ receptor, interleukin (IL)-1β, IL-6, or IL-23. Thus, CD4+ T cells and specific proinflammatory cytokines are required for GP-vaccine-mediated protection. Importantly, retention of protection in the setting of partial CD4+ T depletion suggests a pathway for vaccinating at-risk immunocompromised individuals.

Objective We aimed to establish an easy-to-use screening questionnaire with risk factors and suspected symptoms of COPD for primary health care settings. Methods Based on a nationwide epidemiological study of pulmonary health among adults in mainland China (China Pulmonary Health, CPH study) between 2012 and 2015, participants ≥40 years who completed the questionnaire and spirometry tests were recruited and randomly divided into development set and validation set by the ratio of 2:1. Parameters including sex, age, BMI, residence, education, smoking status, smoking pack-years, biomass exposure, parental history of respiratory diseases and daily respiratory symptoms were initially selected for the development of scoring system. Receiver operating characteristic (ROC) curve, area under curve (AUC), positive and negative predictive values were calculated in development set and validation set. Results After random split by 2:1 ratio, 22443 individuals were assigned to development set and 11221 to validation set. Ten variables were significantly associated with COPD independently in development set after a stepwise selection by multivariable logistic model and used to develop scoring system. The scoring system yielded good discrimination, as measured by AUC of 0.7737, and in the validation set, the AUC was 0.7711. When applying a cutoff point of ≥16, the sensitivity in development set was 0.69 (0.67 − 0.71); specificity 0.72 (0.71 − 0.73), PPV 0.25 (0.24 − 0.26) and NPV 0.94 (0.94 − 0.95). Conclusion We developed and validated a comprehensive screening questionnaire, COPD-CPHS, with good discrimination. The score system still needs to be validated by large cohort in the future. Supplemental data for this article is available online at https://doi.org/10.1080/15412555.2022.2042504 .

Abstract Hypothesis Cochlear microphonic recorded at ear canal (CM‐EC) can be a substitute for the one recorded at round window (CM‐RW). Background Almost all clinics do not measure tone‐burst evoked CM due to technical difficulty although it can provide more information than click evoked CM. Moreover, clinicians like the CM‐EC more than that measured at CM‐RW because CM‐EC is non‐invasive. There is difference between CM‐RW and CM‐EC, for example, CM‐EC is less prominent than CM‐RW, therefore, studying tone‐burst evoked CM‐EC and its relationship with CM‐RW are highly significant and can promote the clinical application of CM‐EC. Method Nine guinea pigs were randomly allocated into three groups, group 1 was not exposed to noise, called normal control. group 2 and group 3 were exposed to the low‐ (0.5–2 kHz) and high‐frequency band‐noise (6–8 kHz) at 120 dB SPL for 1 h, respectively. It was difficulty to record low‐frequency CM due to severe environmental interruption, in current study the recording technology of tone‐burst evoked CM was optimized so that tone‐burst evoked CM was measured across full speech frequency (0.5–8 kHz) in the presence of normal hearing and noise induced hearing loss (NIHL). Results CM‐RW and CM‐EC were successfully recorded across speech frequency. Significant reduction in CM amplitude was observed at 0.5 and 2 kHz in group 2, at 6 and 8 kHz in group 3 as compared to group 1, p

In this study, tin nanoparticles were green synthesized using the aqueous extract of Calendula officinalis. Different techniques such as FE-SEM, XRD, FT-IR, and EDS analysis were used to characterize SnNPs@ C. officinalis. A 21.87 nm was obtained for the crystal size of the tin nanoparticles using XRD analysis. The FE-SEM images show a spherical morphology for SnNPs@ C. officinalis with a range size of 21.63–64.07 for the synthetic nanoparticles. The anti-breast cancer effects of biologically synthesized SnNPs@ C. officinalis against breast cancer cell lines were assessed. The anti-breast cancer properties of the SnNPs@ C. officinalis could significantly remove the MCF7, Hs 319.T, and MCF10 cancer cell lines in a time and concentration-dependent manner by MTT assay. The antioxidant activity of SnNPs@ C. officinalis was determined by the DPPH method. The SnNPs@ C. officinalis showed the highest antioxidant activity according to the IC50 value. It seems the anti-human breast cancer effect of recent nanoparticles is due to their antioxidant effects.

Cyclic-di-GMP transduces extracellular stimuli into intracellular responses to modulate important biological processes. Here, the authors show that AI-2 and bile salts induce cyclic-di-GMP synthesis via YeaJ and YedQ, respectively, to repress the T3SS via a cyclic-di-GMP-responsive T3SS chaperone.

Efficient and inexpensive electrocatalysts play an important role in the hydrogen evolution reaction (HER) of electrolytic water splitting. Herein, Ni2P-MoC/coal-based carbon fiber (Ni2P-MoC/C-CF) self-supporting catalysts were obtained by low-temperature phosphorization and high-temperature carbonization. The Mo source and oxidized coal were uniformly dispersed in the carbon support by electrospinning technology. A precursor of Ni was introduced by the impregnation method. The synergistic effect of MoC and Ni2P may reduce the strong hydrogen adsorption capacity of pure MoC and provide a fast hydrogen release process. In addition, the C-CFs prepared by electrospinning can not only prevent the agglomeration of MoC and Ni2P particles at a high temperature but also provide a self-supporting support for the catalyst. As a result, the catalytic performance of the HER was improved greatly, and a low overpotential of 112 mV at 10 mA cm−2 was exhibited stably by the Ni2P-MoC/C-CFs. This work not only converts coal into coal-based carbon materials but also provides a feasible pathway for the rational design of large-scale molded hydrogen electrocatalysts.

Meningitis due to the fungal pathogen Cryptococcus neoformans is estimated to cause nearly 200,000 deaths annually, mostly in resource-limited regions. We previously identified cryptococcal protein antigens which, when delivered in glucan particles, afford vaccine-mediated protection against an otherwise lethal infection. Many of these proteins exhibit significant homology to other similar cryptococcal proteins leading us to hypothesize that protection may be augmented by immunologic cross-reactivity to multiple members of a protein family. To examine the significance of protein cross-reactivity in vaccination, we utilized strains of Cryptococcus that are genetically deficient in select antigens, yet are still lethal in mice. Vaccination with a protein without homologs (e.g., Mep1 and Lhc1) protected against challenge with wild-type Cryptococcus, but not against a deletion strain lacking that protein. Contrastingly, vaccination with a single chitin deacetylase (Cda) protein protected against the corresponding deletion strain, presumably due to host recognition of one or more other family members still expressed in this strain. Vaccination with a single Cda protein induced cross-reactive antibody and interferon-gamma (IFNγ) immune responses to other Cda protein family members. Paradoxically, we saw no evidence of cross-protection within the carboxypeptidase family of proteins. Factors such as in vivo protein expression and the degree of homology across the family could inform the extent to which vaccine-mediated immunity is amplified. Together, these data suggest a role for prioritizing protein families in fungal vaccine design: increasing the number of immune targets generated by a single antigen may improve efficacy while diminishing the risk of vaccine-resistant strains arising from gene mutations.

Background Chronic cough is a common complaint, but there are no population-based data on its burden in China. We determined the prevalence of chronic cough and its impact on health status in adults stratified by sex, age and the diagnosis of COPD or the presence of small airway dysfunction (SAD). Methods A representative sample of 57 779 Chinese adults aged 20 years or older was recruited and pulmonary function test was measured. Chronic cough was defined as cough lasting for >3 months in each year. Quality of life was assessed by the 12-item Short Form Health Survey (SF-12), and self-reported history of hospital visits was recorded. Results Chronic cough was found in 3.6% (95% CI 3.1–4.1) of Chinese adults, 2.4% (95% CI 1.9–3.1) of those aged 20–49 years and 6.0% (95% CI 5.3–6.8) of those aged 50 years or older. Individuals with chronic cough had an impaired physical component summary (PCS) score of the SF-12 (p

Previous studies have reported religious and non-religious people as having different psychological experiences when visiting sacred landscapes; however, the visual consensus and differences between diverse groups visiting them have rarely been considered. This study used subjective preference evaluation and experimental eye tracking to assess the visual preferences of different groups regarding sacred landscapes. Overall, 48 photos of the Han Chinese Buddhist temples were selected as stimulus materials, including the categories of squares, architecture, waterscapes, and plants. In all, 90 participants were classified into two groups of outsiders and insiders to view the photos. The consensus and differences in their visual preferences and eye movement metrics were evaluated. The results showed that the two groups were more inclined toward the visual preference of religious architectures than the natural landscape that people usually prefer. Another noteworthy discovery revealed the significant differences between the outsiders and the insiders in viewing and evaluating sacred landscapes; the immersion effect explains this result. Specifically, the group with a higher interaction with the environment had greater visual experiences, easier visual information coding, and larger visual exploration range. In addition, this study revealed familiarity with the religious background facilitated achieving a higher consistency between the landscape preference scores and the eye movement metrics. These findings expand the theory of religious environment perception and provided important insights for subsequent research on sacred landscape planning and management.

Ammonia (NH3) synthesis is one of the most important catalytic reactions in energy and chemical fertilizer production, which is of great significance to the sustainable development of society and the economy. The electrochemical nitrogen reduction reaction (eNRR), especially when driven by renewable energy, is generally regarded as an energy-efficient and sustainable process to synthesize NH3 in ambient conditions. However, the performance of the electrocatalyst is far below expectations, with the lack of a high-efficiency catalyst being the main obstacle. Herein, by means of comprehensive spin-polarized density functional theory (DFT) computations, the catalytic performance of MoTM/C2N (TM = 3d transition metal) for use in eNRR was systematically evaluated. Among the results, MoFe/C2N can be considered the most promising catalyst due to its having the lowest limiting potential (−0.26 V) and high selectivity in the context of eNRR. Compared with its homonuclear counterparts, MoMo/C2N and FeFe/C2N, MoFe/C2N can balance the first protonation step and the sixth protonation step synergistically, showing outstanding activity regarding eNRR. Our work not only opens a new door to advancing sustainable NH3 production by tailoring the active sites of heteronuclear diatom catalysts but also promotes the design and production of novel low-cost and efficient nanocatalysts.

Cardiovascular disease (CVD) remains one of the primary causes of morbidity and mortality worldwide. Classic cardiovascular risk factors, such as hypertension, diabetes mellitus (DM), hyperlipidemia, and smoking, have been well identified and given increased attention in clinical practice. However, the incidence and prevalence of CVD remains high, especially in developing countries. Therefore, there has been more attention to non-traditional CVD risk factors such as gut microbiota, sleep disorders, dietary structure, and psychosocial factors in their important roles in the development of CVD. In this review we summarize the association of non-traditional risk factors with CVD with the aim of further reducing the risk of CVD.

Song et al describe and identify monoclonal antibodies that target the SARSCoV-2 Spike protein, including CA521FALA, which demonstrated neutralising potential in vivo and in vitro. They performed structural analysis, which revealed that CA521FALA recognizes an epitope overlapping with angiotensin converting enzyme 2 (ACE2)-binding sites in SARS-CoV-2 Spike protein therefore making it a promising therapeutic antibody.

BackgroundPatients with features of both asthma and chronic obstructive pulmonary disease (COPD) are seen commonly in the clinic but less is known in the general population. We investigated the prevalence and the heterogeneity of COPD with concomitant features of asthma in Chinese adult population.MethodsCOPD was defined as post-bronchodilator ratio of forced expiratory volume in 1s (FEV1) to forced vital capacity of less than the lower limits of normal. COPD with concomitant features of asthma was defined as either COPD with asthma diagnosed by self-reported physician-diagnosis or by presence of current wheeze, or as COPD with high bronchodilator response (HBR) defined as an increase in FEV1 >15% and >400 ml after bronchodilator.ResultsCOPD with concomitant features of asthma was found in 1.62% (95% CI 1.31–2.00) of adults (≥20 years) or in 15.2% (95% CI 13.0–17.7) of COPD patients. Compared with COPD with HBR, COPD with asthma diagnosis or wheeze were older (61.8 ± 1.1 years vs. 47.4 ± 2.8 years, P < 0.001), and with a lower post-bronchodilator FEV1%pred (68.2 ± 2.3 vs. 96.6 ± 3.4, P < 0.001). Age, smoking status, biomass use and allergic rhinitis were associated with increasing prevalence of COPD with asthma diagnosis or wheeze, and had greater impaired health status, more comorbidities and more acute exacerbations in the preceding 12 months.ConclusionsCOPD with concomitant features of asthma is common in people with COPD and those with COPD with asthma diagnosis or wheeze experience worse clinical severity than COPD with HBR. These findings will help toward the definition of the asthma-COPD overlap condition.

Abstract Despite the substantial global burden of human fungal infections, there are no approved fungal vaccines to protect at risk individuals. Here, we review the progress that has been made and the challenges that lie ahead in the quest towards efficacious fungal vaccines. In mouse studies, protection has been achieved with vaccines directed against fungal pathogens, including species of Candida, Cryptococcus, and Aspergillus, that most commonly cause life-threatening human disease. Encouraging results have been obtained with vaccines composed of live-attenuated and killed fungi, crude extracts, recombinant subunit formulations, and nucleic acid vaccines. Novel adjuvants that instruct the immune system to mount the types of protective responses needed to fight mycotic infections are under development. Candidate vaccines include those that target common antigens expressed on multiple genera of fungi thereby protecting against a broad range of mycoses. Encouragingly, three vaccines have reached human clinical trials. Still, formidable obstacles must be overcome before we will have fungal vaccines licensed for human use.

Abstract Background To analyze the risk factors for hypertension in different age groups of urban and rural residents in Tianjin. Methods A total of 33,997 people (35–75 years old) from 13 community health service centers and primary hospitals in Tianjin participated in this study. They were divided into the youth group (≤ 40 years old), middle-aged group (41–65 years old), and elderly group (> 65 years old). Then, a questionnaire survey was administered, followed by physical and blood biochemical examinations. The demographic characteristics and prevalence were recorded and counted. Subsequently, risk factors were analyzed using univariate and stepwise multivariate logistic regression analysis. Results In the youth, middle-aged, and elderly groups, the prevalence rate of hypertension was 18.65, 51.80, and 76.61%, respectively. Logistic regression analysis showed that obesity(OR: 3.263, 95% CI: 1.039–1.656), men (OR: 2.117, 95% CI: 1.691–2.651), diabetes (OR: 1.978, 95% CI: 1.398–2.799), high triglycerides(OR 1.968 95% CI: 1.590–2.434) and family history of stroke (OR: 1.936, 95% CI: 1.287–2.911) are the five factors in youth. In middle-aged group, the significantly associating factors were obesity (OR: 2.478, 95% CI: 2.330–2.636), diabetes (OR: 2.173, 95% CI: 1.398–2.799), family history of stroke (OR: 1.808, 95% CI: 1.619–2.020), maleness (OR: 1.507, 95% CI: 1.412–1.609),Hypertriglyceridemia (OR 1.490 95% CI: 1.409–1.577),family history of cardiovascular disease (OR: 1.484, 95% CI: 1.307–1.684),Hypercholesterolemia (OR 1.228 95% CI: 1.160–1.299). In the elderly group, obesity (OR: 2.104, 95% CI: 1.830–2.418), family history of strokes (OR: 1.688, 95% CI: 1.243–2.292), diabetes mellitus (OR: 1.544, 95% CI: 1.345–1.773), family history of cardiovascular disease (OR: 1.470, 95% CI: 1.061–2.036), hypertriglyceridemia (OR: 1.348, 95% CI: 1.192–1.524) increased the risk for hypertension. Waist circumference (WC) and waist-to-height ratio (WHtR) increased with age, and the value of these two measures for predicting hypertension was better than BMI in middle-aged group. Conclusion Obesity is the most important risk factor for hypertension in all age groups. Diabetes, family history of strokes and high triglyceride were also significant risk factors for all age groups. There was a gender difference between the young and middle-aged groups, with men more likely to hypertension. Waist circumference (WC) and waist-to-height ratio (WHtR) were better predictors of hypertension than BMI in middle-aged group.

Owing to their special physical and chemical properties, nanomaterials with core–shell structures have been extensively synthesized and widely studied in the field of energy storage and conversion [...]

The small molecule AI-2 acts as a quorum sensing signal, mediating communication within and between many bacterial species. Here, the authors identify a new type of AI-2 receptor, consisting of a dCACHE domain that is present in many bacterial and archaeal proteins.

In this study, rice bran protein–chlorogenic acid (RBP–CA) emulsion was subjected to an ultrasonic-assisted treatment technique. The encapsulation efficiency and loading capacity of chlorogenic acid (CA), and the morphology, particle size, zeta (ζ)-potential, atomic force microscopy image, viscosity, turbidity, and interfacial protein content of the emulsion under different ultrasonic power were investigated. The results revealed that the emulsion exhibited an encapsulation efficiency and loading capacity of 86.26 ± 0.11% and 17.25 ± 0.06 g/100 g, respectively, at an ultrasonic power of 400 W. In addition, the size of the emulsion droplets decreased and became more evenly distributed. Furthermore, the viscosity of the emulsion decreased significantly, and it exhibited a turbidity and interfacial protein content of 24,758 and9.34 mg/m2, respectively. Next, the storage, oxidation, thermal, and salt ion stabilities of the emulsion were evaluated. The results revealed that the ultrasonic-assisted treatment considerably improved the stability of the emulsion.

Calenduloside E (CE) is a saponin isolated from Aralia elata (Miq) Seem, which has anti-cardiovascular disease effects. This study aims to evaluate the anti-myocardial ischemia-reperfusion injury (MIRI) mechanisms of CE and regulation of BAG3 on calcium overload. We adopted siRNA to interfere with BAG3 expression in H9c2 cardiomyocytes and used adenovirus to interfere with BAG3 expression (Ad-BAG3) in primary neonatal rat cardiomyocytes (PNRCMs) to clarify the role of BAG3 in mitigating MIRI by CE. The results showed that CE reduced calcium overload, and Ad-BAG3 had a significant regulatory effect on L-type Ca2+ channels (LTCC) but no effects on other calcium-related proteins. And BAG3 and LTCC were colocalized in myocardial tissue and BAG3 inhibited LTCC expression. Surprisingly, CE had no regulatory effect on LTCC mRNA, but CE promoted LTCC degradation through the autophagy-lysosomal pathway rather than the ubiquitination-protease pathway. Autophagy inhibitor played a negative regulation of cardiomyocyte contraction rhythm and field potential signals. Ad-BAG3 inhibited autophagy by regulating the expression of autophagy-related proteins and autophagy agonist treatment suppressed calcium overload. Therefore, CE promoted autophagy through BAG3, thereby regulating LTCC expression, inhibiting calcium overload, and ultimately reducing MIRI.

Myocardial infarction (MI) is the most frequent end-point of cardiovascular pathology, leading to higher mortality worldwide. Due to the particularity of the heart tissue, patients who experience ischemic infarction of the heart, still suffered irreversible damage to the heart even if the vascular reflow by treatment, and severe ones can lead to heart failure or even death. In recent years, several studies have shown that microRNAs (miRNAs), playing a regulatory role in damaged hearts, bring light for patients to alleviate MI. In this review, we summarized the effect of miRNAs on MI with some mechanisms, such as apoptosis, autophagy, proliferation, inflammatory; the regulation of miRNAs on cardiac structural changes after MI, including angiogenesis, myocardial remodeling, fibrosis; the application of miRNAs in stem cell therapy and clinical diagnosis; other non-coding RNAs related to miRNAs in MI during the past 5 years.

The associations of long-term exposure to various constituents of fine particulate matter (≤2.5 μm in aerodynamic diameter, PM2.5) air pollution with lung function were not clearly elucidated in developing countries. The aim was to evaluate the associations of long-term exposure to main constituents of PM2.5 with lung function in China. This is a nationwide, cross-sectional analysis among 50,991 study participants from the China Pulmonary Health study. Multivariable linear regression models were used to obtain differences of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, peak expiratory flow (PEF), and forced expiratory flow at 25–75% of exhaled FVC (FEF25-75%) associated with an interquartile range (IQR) change of PM2.5 or its constituents. Residential annual PM2.5 levels varied from 26 μg/m3 to 92 μg/m3 (average: 53 μg/m3). An IQR increase of PM2.5 concentrations was associated with lower FEV1 (19.82 mL, 95% CI: 11.30–28.33), FVC (17.45 mL, 95% CI: 7.16–27.74), PEF (86.64 mL/s, 95% CI: 59.77–113.52), and FEF25-75% (31.93 mL/s, 95% CI: 16.64–47.22). Black carbon, organic matter, ammonium, sulfate, and nitrate were negatively associated with most lung function indicators, with organic matter and nitrate showing consistently larger magnitude of associations than PM2.5 mass. This large-scale study provides first-hand epidemiological evidence that long-term exposure to ambient PM2.5 and some constituents, especially organic matter and nitrate, were associated with lower large- and small- airway function.

Liquid crystals (LCs) are appealing biomaterials for applications in bone regenerative medicine due to their tunable physical properties and anisotropic viscoelastic behavior. This study reports a novel composite poly (L-lactide) (PLLA) scaffold that is manufactured by a simple electrospinning and biomineralization technique that precisely controls the fibrous structure in liquid LC phase. The enriched-LC composites have superior mineralization ability than neat PLLA; furthermore BMSC cells were inoculated onto the HAP-PLLA/LC with hydroxyapatite (HAP) composite scaffold to test the capability for osteogenesis in vitro. The results show that the PLLA/LC with HAP produced by mineralization leads to better cell compatibility, which is beneficial to cell proliferation, osteogenic differentiation, and expression of the angiogenic CD31 gene. Moreover, in vivo studies showed that the HAP-PLLA/LC scaffold with a bone-like environment significantly accelerates new and mature lamellar bone formation by development of a microenvironment for vascularized bone regeneration. Thus, this bionic composite scaffold in an LC state combining osteogenesis with vascularized activities is a promising biomaterial for bone regeneration in defective areas.

Objective: This work was conducted in order to study the effect of the lower genital tract (vaginal and cervical canal) microbiota on pregnancy outcomes of reproductive-aged women receiving embryo transfer.Study design: A total of 150 reproductive-aged patients who received the first fresh in vitro fertilization-embryo transfer (IVF-ET) were included in the study. Samples from the vagina and cervical site of each patient were collected separately using sterile swabs before ET. Genomic DNA was pyrosequenced for the V3–V4 regions of the 16S ribosomal RNA gene. Further bioinformatics analysis was performed using QIIME and R package. Pregnancy outcomes were followed and analyzed to compare differences in microbial composition.Results: The cervical microbiota had a higher Shannon index than the vaginal microbiota, and the microbial composition was different between the two sites. However, the Sorenson index between the two sites within the same individual was 0.370 (0.309–0.400). A total of 89 patients achieved clinical pregnancy after ET, while 61 failed. The Shannon indices and the microbial community of both vaginal and cervical microbiota between pregnant and non-pregnant groups were not significantly different. The relative abundance of Lactobacillus in the vagina and cervical canal did not differ between the two groups. Linear discriminant analysis, random forest analysis, and receiver-operating characteristic curve analysis showed that Bifidobacterium, Prevotella, and Lactobacillus iners in the vagina, as well as Solanum torvum, Fusobacterium, and Streptococcus in the cervix, may be negatively associated with clinical pregnancy after IVF.Conclusion: The cervical microbiota was more diverse than the vaginal microbiota, but because of anatomical continuity, there was a correlation between the two sites. The microbial composition of the vagina and cervical canal may influence the outcome of IVF-ET, but more samples are needed to verify this conclusion.

Abstract Background Cardiotoxicity remains an important concern in drug discovery and clinical medication. Meanwhile, Sophora tonkinensis Gapnep. (S. tonkinensis) held great value in the clinical application of traditional Chinese medicine, but cardiotoxic effects were reported, with matrine, oxymatrine, cytisine, and sophocarpine being the primary toxic components. Methods In this study, impedance and extracellular field potential (EFP) of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were recorded using the cardio non-labeled cell function analysis and culture system (Cardio-NLCS). The effects of matrine, oxymatrine, cytisine, and sophocarpine (2, 10, 50 μM) on cell viability; level of lactate dehydrogenase (LDH), creatine kinase MB isoenzyme (CK-MB), and cardiac troponin I (CTn-I); antioxidant activities; production of reactive oxygen species (ROS) and malondialdehyde (MDA); and disruption of intracellular calcium homeostasis were also added into the integrated assessment. Results The results showed that matrine and sophocarpine dose-dependently affected both impedance and EFP, while oxymatrine and cytisine altered impedance significantly. Our study also indicated that cardiotoxicity of matrine, oxymatrine, cytisine, and sophocarpine was related to the disruption of calcium homeostasis and oxidative stress. Four alkaloids of S. tonkinensis showed significant cardiotoxicity with dose dependence and structural cardiotoxicity synchronized with functional changes of cardiomyocytes. Conclusions This finding may provide guidance for clinical meditation management. Furthermore, this study introduced an efficient and reliable approach, which offers alternative options for evaluating the cardiotoxicity of the listed drugs and novel drug candidates.

Background/Aims: Total saponins of Aralia elata (Miq) Seem (AS) from the Chinese traditional herb Long ya Aralia chinensis L. reportedly provide cardioprotective effects, but the exact mechanisms require further study. Previous studies have showed that myocardial ischemia/ reperfusion injury (MIRI) was related to calcium homeostasis imbalance and endoplasmic reticulum stress (ERS). Thus, this study aimed to demonstrate protective effects of AS on MIRI. Methods: After administrating AS for 5 days, the left anterior descending artery coronary artery of Sprague-Dawley (SD) rats was ligated for 30 min. After 48 h of reperfusion, haemodynamics, Evans blue/ 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining, masson staining and the levels of lactate dehydrogenase (LDH) and creatine kinase (CK), superoxide dismutase (SOD), malondialdehyde (MDA) were detected to assess MIRI. ATPase activity and Western Blot were used to study the mechanisms. Results: Compared with IR group, AS treatment groups could significantly reduce myocardial infarct size; improve myocardial pathologic progress; decrease content of LDH, CK, and MDA; increase content of SOD; and restore the activities of Ca2+-Mg2+-ATPase, Na+-K+-ATPase, sarcoplasmic reticulum Ca2+-ATPases (SERCA), and calcineurin (CaN). AS treatment groups also significantly up-regulated the expression of GRP78, C/EBP homologous protein (CHOP), and Bax, and down-regulated the expression of Bcl-2, all similar to the effects of ERS. Conclusion: These findings illustrated that AS could prevent myocardial ischemia/reperfusion injury and reduce calcium homeostasis imbalance and ERS-related apoptosis.

Myocardial ischemia is a high-risk disease among middle-aged and senior individuals. After thrombolytic therapy, heart tissue can potentially suffer further damage, which is called myocardial ischemia-reperfusion injury (MIRI). At present, the treatment methods and drugs for MIRI are scarce and cannot meet the current clinical needs. The mechanism of MIRI involves the interaction of multiple factors, and the current research hotspots mainly include oxidative stress, inflammation, calcium overload, energy metabolism disorders, pyroptosis, and ferroptosis. Traditional Chinese medicine (TCM) has multiple targets and few toxic side effects; clinical preparations containing Panax ginseng C. A. Mey., Panax notoginseng (Burk.) F. H. Chen, Aralia chinensis L., cardioprotection, and other Chinese herbal medicines have been used to treat patients with coronary heart disease, angina pectoris, and other cardiovascular diseases. Studies have shown that saponins are the main active substances in TCMs containing Panax ginseng C. A. Mey., Panax notoginseng (Burk.) F. H. Chen, Aralia chinensis L., and Radix astragali. In the present review, we sorted the saponin components with anti-MIRI effects and their regulatory mechanisms. Each saponin can play a cardioprotective role via multiple mechanisms, and the signaling pathways involved in different saponins are not the same. We found that more active saponins in Panax ginseng C. A. Mey. are mainly dammar-type structures and have a strong regulatory effect on energy metabolism. The highly active saponin components of Aralia chinensis L. are oleanolic acid structures, which have significant regulatory effects on calcium homeostasis. Therefore, saponins in Chinese herbal medicine provide a broad application prospect for the development of highly effective and low-toxicity anti-MIRI drugs.

Rice is sensitive to low temperatures, specifically at the booting stage. Chilling tolerance of rice is a quantitative trait loci that is governed by multiple genes, and thus, its precise identification through the conventional methods is an arduous task. In this study, we investigated the candidate genes related to chilling tolerance at the booting stage of rice. The F2 population was derived from Longjing25 (chilling-tolerant) and Longjing11 (chilling-sensitive) cross. Two bulked segregant analysis pools were constructed. A 0.82 Mb region containing 98 annotated genes on chromosomes 6 and 9 was recognized as the candidate region associated with chilling tolerance of rice at the booting stage. Transcriptomic analysis of Longjing25 and Longjing11 revealed 50 differentially expressed genes (DEGs) on the candidate intervals. KEGG pathway enrichment analysis of DEGs was performed. Nine pathways were found to be enriched, which contained 10 DEGs. A total of four genes had different expression patterns or levels between Longjing25 and Longjing11. Four out of the 10 DEGs were considered as potential candidate genes for chilling tolerance. This study will assist in the cloning of the candidate genes responsible for chilling tolerance and molecular breeding of rice for the development of chilling-tolerant rice varieties.