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Summary: Background: Heterologous vaccine schedules have been recommended to provide superior immunity and protection against emergent SARS-CoV-2 variants of concern. We aimed to evaluate the safety, immunogenicity, and efficacy of an mRNA COVID-19 vaccine RQ3013 compared with adenoviral vectored vaccine Ad5-nCoV and protein subunit vaccine ZF2001 as the fourth dose in adults primed with three doses of inactivated vaccines in China. Methods: We conducted a double-blinded, randomised, controlled, phase 3b trial among healthy Chinese adults at Lancang County, Yunnan, China. Adults who had received three doses of inactivated COVID-19 vaccines at least 6 months prior were randomly allocated (3:1:1) to receive heterologous boosters with RQ3013, Ad5-nCoV, or ZF2001. We assessed safety within 28 days post boost and the serum geometric mean titres (GMTs) of neutralising antibodies (NAbs) against the live SARS-CoV-2 omicron variant BA.5 on day 14 post-boost. We used Poisson regression to assess the vaccine efficacy against the first episode of virologically confirmed symptomatic COVID-19 occurring at least 7 days post boost. Subgroup analyses categorized by age and sex were also performed for safety and immunogenicity outcomes. This trial has been registered with the Chinese Clinical Trial Registry (ChiCTR2200065281) and is now complete. Findings: Between December 12 and December 18, 2022, a total of 1382 adults were screened, and 1250 were enrolled and randomly assigned to receive one dose of RQ3013 (n = 750), Ad5-nCoV (n = 250), or ZF2001 (n = 250). Although solicited adverse reactions within 28 days post boost were more frequent in the RQ3013 group (175 [23.3%]) compared to the control groups (24 [9.6%] in both the Ad5-nCOV and ZF2001 groups, P 0.05). On day 14 post-boost, RQ3013 (GMT 69.14, 95% CI 47.90–99.81) elicited 4.8-fold and 5.6-fold higher concentrations of NAbs against BA.5 than did Ad5-nCoV (14.37, 7.78–26.56) and ZF2001 (12.21, 5.13–29.06), respectively. On day 28 post-boost, RQ3013 demonstrated a relative efficacy of 62.2% (95% CI 13.7–83.1, P = 0.02) compared to Ad5-nCoV, and of 69.0% (33.5–85.7, P = 0.002) compared to ZF2001. Interpretation: The administrations of all the three heterologous boosters were well tolerated. The heterologous prime-boost regimen with RQ3013 elicited superior immune responses and demonstrated better protection against symptomatic SARS-CoV-2 infections compared with Ad5-nCoV or ZF2001, supporting the use of RQ3013 as a booster vaccination in adults. Funding: Yunnan Province Science and Technology Department (grant no.202302AA310047).

Taking gob-side entry retaining in Sichuan Coal Group Xuyong No.1 mine as an engineering background, the displacement inverse analysis method is used to calibrate the physical and mechanical parameters test results of coal and rock, and the numerical simulation method is used to analyze the mine pressure distribution law of gob-side entry retaining roadway. Field observation shows that during the working face mining, the maximum relative displacement of roadway roof and floor is 743 mm. Roof subsidence is the main displacement mode of roadway roof and floor. The average roof subsidence is 3.6 times of floor heave, and the numerical simulation result is 3.5 times. The parameter calibration results show that the reduction of elastic modulus and cohesion has a significant impact on the roof and floor approach. At the same calculation step, the roof and floor approach increases with the decrease of elastic modulus and cohesion. When the elastic modulus is reduced to 20%, the maximum value of roof and floor approach increases to 800 mm. The numerical simulation results show that the abutment pressure at the high wall of gob-side entry retaining roadway at the rear of mining face increases significantly, and the abutment pressure distribution is low on both sides and “convex” with the middle height, and the peak value of abutment pressure increases with the advance of working face. The influence range of the average leading abutment pressure of the working face is 77 m.

Abstract. Background:. Cluster of differentiation 8 (CD8 T) cells play critical roles in eradicating human immunodeficiency virus (HIV)-1 infection, but little is known about the effects of T cells expressing CD8 at low levels (CD8low) or high levels (CD8high) on HIV-1 replication inhibition after HIV-1 invasion into individual. Methods:. Nineteen patients who had been acutely infected with HIV-1 (AHI) and 20 patients with chronic infection (CHI) for ≥2 years were enrolled in this study to investigate the dynamics of the quantity, activation, and immune responses of CD3+CD8low T cells and their counterpart CD3+CD8high T cells at different stages of HIV-1 infection. Results:. Compared with healthy donors, CD3+CD8low T cells expanded in HIV-1-infected individuals at different stages of infection. As HIV-1 infection progressed, CD3+CD8low T cells gradually decreased. Simultaneously, CD3+CD8high T cells was significantly reduced in the first month of AHI and then increased gradually as HIV-1 infection progressed. The classical activation of CD3+CD8low T cells was highest in the first month of AHI and then reduced as HIV-1 infection progressed and entered the chronic stage. Meanwhile, activated CD38−HLA-DR+CD8low T cells did not increase in the first month of AHI, and the number of these cells was inversely associated with viral load (r = −0.664, P = 0.004) but positively associated with the CD4 T-cell count (r = 0.586, P = 0.014). Increased programmed cell death protein 1 (PD-1) abundance on CD3+CD8low T cells was observed from the 1st month of AHI but did not continue to be enhanced, while a significant T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif (ITIM) domains (TIGIT) abundance increase was observed in the 12th month of infection. Furthermore, increased PD-1 and TIGIT abundance on CD3+CD8low T cells was associated with a low CD4 T-cell count (PD-1: r = −0.456, P = 0.043; TIGIT: r = −0.488, P = 0.029) in CHI. Nonetheless, the nonincrease in PD-1 expression on classically activated CD3+CD8low T cells was inversely associated with HIV-1 viremia in the first month of AHI (r = −0.578, P = 0.015). Notably, in the first month of AHI, few CD3+CD8low T cells, but comparable amounts of CD3+CD8high T cells, responded to Gag peptides. Then, weaker HIV-1-specific T-cell responses were induced in CD3+CD8low T cells than CD3+CD8high T cells at the 3rd and 12th months of AHI and in CHI. Conclusions:. Our findings suggest that CD3+CD8low T cells play an anti-HIV role in the first month of infection due to their abundance but induce a weak HIV-1-specific immune response. Subsequently, CD3+CD8low T-cell number decreased gradually as infection persisted, and their anti-HIV functions were inferior to those of CD3+CD8high T cells.

Abstract Aims Acute viral myocarditis (AVMC) is the aetiology of heart failure (HF) with few specific treatments. The improvement of left ventricular ejection fraction (LVEF) is a critical predictor for the prognosis of AVMC. LCZ696 is a drug used in HF to improve LVEF, with a few research on AVMC. In this research, we evaluated the effects and mechanism of LCZ696 in improving LVEF in AVMC. Methods Eighty 4‐week‐old male BALB/c mice were randomly divided into four groups of 20: Sham; Sham + LCZ696 (60 mg/kg/d); AVMC; AVMC + LCZ696. The above experiments were repeated by CVB3‐infected HL‐1 and Mdivi‐1 to down‐regulated dynamin‐related protein 1(Drp1). Adeno‐associated virus 9 (AAV9) with enhanced green fluorescent proteins (GFP) was injected to produce Drp1‐overexpression mice and set up four groups: AVMC group, AVMC + AAV group, AVMC + LCZ696 group, and AVMC + LCZ696 + AAV group (n = 20 in each group). LVEF was evaluated by echocardiography at a similar heart rate (HR) at d7, Drp1 (p‐Drp1), inflammation and apoptosis by histology and Western blot (WB), and mitochondrial by electron microscopy. Results Cardiac function were injured in AVMC that LCZ696 reversed (LVEF, %: Sham: 68.99 ± 9.67; Sham + LCZ696: 71.96 ± 6.20; AVMC: 30.95 ± 6.40*; AVMC + LCZ696: 68.99 ± 9.67*#, *P

Taxus cuspidata S. et Z. is a precious species of frigid zone plant belonging to the Taxaceae family, which possesses anticancer, anti-inflammatory, hypoglycemic, and antibacterial pharmacological properties. While taxane extracted from Taxus chinensis has been reported to elicit antioxidant activities, whether Taxus cuspidata S. et Z. has skin-protective actions against injuries remained unknown. This study aims to explore the pharmacological effects of three Taxus extracts on skin melanin deposition, oxidation, inflammation, and allergy so as to provide new ideas for the prevention and treatment of various diseases related to skin damage.

We report here a series of alkyl group-modified trimesic amide molecules (TAs) with excellent anion transport activities. Among them, TA6, with the highest ion transport activity and excellent selectivity, efficiently transports anions across the membrane in the order of ClO4− > I− > NO3− > Br− > Cl−, with an EC50 value as low as 17.6 nM (0.022 mol% relative to lipid molecules) for ClO4−, which outperforms other anions by 5- to 22-folds and manifests as the best perchlorate transporter ever reported.

This paper introduces ‘SkeletonCLIP++’, an extension of our prior work in human action recognition, emphasizing the use of semantic information beyond traditional label-based methods. The innovation, ‘Weighted Frame Integration’ (WFI), shifts video feature computation from averaging to a weighted frame approach, enabling a more nuanced representation of human movements in line with semantic relevance. Another key development, ‘Contrastive Sample Identification’ (CSI), introduces a novel discriminative task within the model. This task involves identifying the most similar negative sample among positive ones, enhancing the model’s ability to distinguish between closely related actions. Incorporating the ‘BERT Text Encoder Integration’ (BTEI) leverages the pre-trained BERT model as our text encoder to refine the model’s performance. Empirical evaluations on HMDB-51, UCF-101, and NTU RGB+D 60 datasets illustrate positive improvements, especially in smaller datasets. ‘SkeletonCLIP++’ thus offers a refined approach to human action recognition, ensuring semantic integrity and detailed differentiation in video data analysis.

This study examines a versatile polymer known as polysurfactant, which is synthesized by co-polymerizing flexible acrylamide and sodium acrylate hydrocarbon chain. The polymer serves as a backbone and possesses active functional groups. Notably, the polysurfactant exhibits superior plugging and flooding abilities compared to conventional polymers. The primary objective of this paper is to investigate the properties and oil displacement characteristics of the polysurfactant through indoor physical simulation experiments. The results demonstrate that the multi-branched structure of the polysurfactant enhances its ability to associate, leading to the formation of a unique spatial network structure. The inclusion of multi-branched structures notably amplifies the association effect. The critical concentration for the association is estimated to be around 800 mg/L, at which juncture the polysurfactant exhibits a viscosity retention rate surpassing 90% subsequent to shearing. Furthermore, this spatial network structure exhibits self-recovery capabilities after experiencing shear failure and displaying strong viscosity and shear resistance. In addition, the concentration of the polysurfactant can control the hydrodynamic feature size, which shows its adaptability in regulation and oil-repelling functions at reservoir permeabilities ranging from 500 to 2000 × 10−3 μm2 with resistance coefficients ranging from 108 to 320. During the microscopic oil displacement process, the polysurfactant exerts a significant impact on mobility control, while the elastic pull clearly demonstrates a commendable viscoelastic oil displacement effect. The polysurfactant exhibits a specific degree of emulsification capability towards crude oil, leading to the emulsion exhibiting typical pseudoplastic fluid characteristics. The utilization of emulsification transportation and emulsification blockage contributes to the enhancement of oil recovery. As a result, the polysurfactant exhibits multifaceted capabilities, encompassing profile control, flooding, and plugging, owing to its unique structural characteristics. Through the implementation of a field test focused on flooding in the Daqing Oilfield, a significant enhancement in the recovery rate of 10.85% is observed, accompanied by a favorable input–output ratio of 1:3.86, thereby generating significant economic advantages.

Periodontitis and diabetes have a bidirectional link, making therapeutic treatment of periodontitis and diabetes challenging. Numerous factors, including microbes, inflammatory cytokines, immune cell activity, glucose levels, and metabolic disorders, contribute to the bidirectional relationship of periodontitis and diabetes. Basic periodontal treatment, medication, surgical treatment, and combined treatment are the most widely used treatments, but their efficacy are limited. Because of their capacity to support bone remodeling and tissue regeneration and restoration, reduce blood glucose levels, restore islet function, and ameliorate local and systemic inflammation, stem cell-derived exosomes have emerged as a possible therapeutic. In this review, we summarize the utilization of stem cell-derived exosomes in periodontitis and diabetes，discuss their potential mechanisms in periodontitis and diabetes bidirectional promoters. It provides some theoretical basis for using stem cell-derived exosomes to regulate the bidirectional link between periodontitis and diabetes.

This was a phase 1 dose-escalation study of ZR202-CoV, a recombinant protein vaccine candidate containing a pre-fusion format of the spike (S)-protein (S-trimer) combined with the dual-adjuvant system of Alum/CpG. A total of 230 participants were screened and 72 healthy adults aged 18–59 years were enrolled and randomized to receive two doses at a 28-day interval of three different ZR202-CoV formulations or normal saline. We assessed the safety for 28 days after each vaccination and collected blood samples for immunogenicity evaluation. All formulations of ZR202-CoV were well-tolerated, with no observed solicited adverse events ≥ Grade 3 within 7 days after vaccination. No unsolicited adverse events ≥ Grade 3, or serious adverse events related to vaccination occurred as determined by the investigator. After the first dose, detectable immune responses were observed in all subjects. All subjects that received ZR202-CoV seroconverted at 14 days after the second dose by S-binding IgG antibody, pseudovirus and live-virus based neutralizing antibody assays. S-binding response (GMCs: 2708.7 ~ 4050.0 BAU/mL) and neutralizing activity by pseudovirus (GMCs: 363.1 ~ 627.0 IU/mL) and live virus SARS-CoV-2 (GMT: 101.7 ~ 175.0) peaked at 14 days after the second dose of ZR202-CoV. The magnitudes of immune responses compared favorably with COVID-19 vaccines with reported protective efficacy.

We analyze the epidemiological characteristics of varicella and breakthrough cases in Qing Yang City, Gansu Province, and provide a basis for the formulation of varicella prevention and control policies. Varicella and breakthrough cases, public health emergency events in Qing Yang City during 2014–2022 were obtained from the China Disease Prevention and Control information System, and the immunization history of the cases were collected from the Gansu Provincial Immunization Planning Information System, descriptive epidemiological analysis of the obtained information was then performed. A total of 6961 cases of varicella were reported in Qing Yang City from 2014 to 2022, yielding an annual incidence of 36.99 cases per 100 000 population. The incidence increased from 19.74/100,000 in 2014 to 35.97/100,000 in 2022; the incidence peaks were observed from May to July and from November to January of the next year. The reported incidence is higher in males (37.70/100,000) than in females (31.54/100,000), and the main age groups were 4 ~ 6 years old (241.98/100,000), 7 ~ 9 years old (142.39/100,000), 10 ~ 14 years old (101.99/100,000). There were 1975 breakthrough cases, accounting for 28.4% of the total reported cases; the majority of patients were students, children in nursery care and scattered children; a total of 10 outbreaks of varicella were reported in primary schools (40.0%), secondary schools (30.0%), kindergartens (20.0%) and high schools (10.0%). The incidence of varicella showed an increasing trend, children and students are high-risk population. It is suggested that varicella vaccine should be included into the immunization program, and the vaccination rate of two-dose of varicella vaccine should be increased for age-eligible children, and varicella surveillance should be strengthened.

Affordable, polyvalent meningococcal vaccines are needed for use in emergency reactive immunization campaigns. A phase IV randomized, observer-blind, controlled study compared the safety and immunogenicity of a quadrivalent meningococcal polysaccharide vaccine (MPV-4, MPV ACYW135) and quadrivalent meningococcal ACWY conjugate vaccine (MCV-4, Menactra®). Healthy, 2- to 10-year-old children in Bamako, Mali, were randomized 1:1 to receive one dose of MPV-4 or MCV-4. Safety outcomes were evaluated for 6 months post-immunization. Immunogenicity for all serogroups was assessed for non-inferiority between MPV-4 and MCV-4 30 days post immunization by serum bactericidal antibody assay using baby rabbit complement (rSBA). From December 2020 to July 2021, 260 healthy subjects were consented and randomized. At Day 30 post-immunization, the proportions of subjects with rSBA titers ≥ 128 for all serogroups in the MPV-4 group were non-inferior to those in MCV-4 group. The proportions of subjects with rSBA ≥ 4-fold increase and rSBA titers ≥ 8 for all serogroups were similar among vaccine groups (P > .05). Geometric Mean Titers and Geometric Mean Fold Increases for all serogroups in both vaccine groups were similar (P > .05). Few local and systemic post-immunization reactions of similar severity and duration were observed within 7 days and were similar in both groups (P > .05). All resolved without sequelae. Unsolicited adverse events were similar in both groups regarding relationship to study vaccine, severity and duration. No serious adverse events were reported during the study period. MPV ACYW135 showed a non-inferior immunogenicity profile and a comparable reactogenicity profile to MCV-4 in Malian children aged 2–10 years. Clinical Trial Registration: NCT04450498.

Accumulating evidence suggests that circRNAs play crucial roles in human diseases. CircRNA-disease association prediction is extremely helpful in understanding pathogenesis, diagnosis, and prevention, as well as identifying relevant biomarkers. During the past few years, a large number of deep learning (DL) based methods have been proposed for predicting circRNA-disease association and achieved impressive prediction performance. However, there are two main drawbacks to these methods. The first is these methods underutilize biometric information in the data. Second, the features extracted by these methods are not outstanding to represent association characteristics between circRNAs and diseases. In this study, we developed a novel deep learning model, named iCircDA-NEAE, to predict circRNA-disease associations. In particular, we use disease semantic similarity, Gaussian interaction profile kernel, circRNA expression profile similarity, and Jaccard similarity simultaneously for the first time, and extract hidden features based on accelerated attribute network embedding (AANE) and dynamic convolutional autoencoder (DCAE). Experimental results on the circR2Disease dataset show that iCircDA-NEAE outperforms other competing methods significantly. Besides, 16 of the top 20 circRNA-disease pairs with the highest prediction scores were validated by relevant literature. Furthermore, we observe that iCircDA-NEAE can effectively predict new potential circRNA-disease associations.

With the rapid development of the times, people have entered the era of intelligence, and the application of big data algorithms is becoming increasingly widespread. The satisfaction of consumers in online shopping is closely related to communication and interaction during shopping. Based on this, this article studies the impact of online e-commerce interaction on consumer satisfaction based on big data algorithms. This article introduces the mediating variable of consumer satisfaction from the perspective of interaction, constructs a model between interaction and trust, and studies the internal impact mechanism of online interaction on consumer satisfaction in online shopping. This article takes the JD interactive shopping platform as the research object, and analyzes and explores the target consumer satisfaction of the women's clothing interactive shopping platform. Analyzed the impact of interaction on merchant qualifications and service satisfaction evaluations, store size, and logistics of purchased goods. The research results indicate that the normalization coefficients of the H1a and H1b pathways are 0.131 and 0.118, respectively, which are slightly smaller, indicating that the impact of perceived risk on consumer satisfaction is not significant. Meanwhile, the CR in H1 is a positive number and the direction of influence is positive, which is contrary to the assumption. Therefore, it is necessary to calibrate the initial model. After correction, the GFI value is 0.816, AGFI value is 0.825, RMSEA value is 0.042, TFI value is 0.930, CFI value is 0.955, PGFI value is 0.718, and PNFI value is 0.810. The degree is within an acceptable range. Therefore, when implementing interactive shopping, e-commerce companies need to create a good shopping environment for the implementation of interactive activities between sellers and customers. The impact of online e-commerce interaction based on big data algorithms on consumer satisfaction is a hot topic. Personalized recommendations can improve consumer satisfaction and loyalty, but data privacy and security issues are also receiving increasing attention. In addition, it is also necessary to consider the fairness and bias issues of the algorithm, as well as the transparency issues of data analysis and decision-making. On the premise of ensuring data privacy and security, it is necessary to improve the fairness and transparency of algorithms to improve consumer satisfaction and trust, and achieve sustainable development.

BackgroundSkin and Soft Tissue Infections (SSTIs) Surveillance Network of S. aureus In Pediatrics in China was established in 2009 to routinely report epidemiological changes. We aimed to monitor the present antibiotic sensitivity and molecular characteristics of S. aureus and methicillin-resistant S. aureus (MRSA) from SSTIs in children nationwide and track the changes over the past decade.MethodsPatients diagnosed with SSTIs from the dermatology departments of 22 tertiary pediatric hospitals in seven geographical regions of China were recruited continuously from May 2019 to August 2021. S. aureus was isolated, and its sensitivity to 15 antimicrobials was evaluated using the broth microdilution method. The molecular characteristics of the MRSA isolates were determined through multilocus sequence typing (MLST) and staphylococcal cassette chromosome mec (SCCmec) typing. The presence of the Panton–Valentine leukocidin gene (pvl) was determined.ResultsThe detection rate of S. aureus was 62.57% (1379/2204), among which MRSA accounted for 14.79% (204/1379), significantly higher than the result in previous study in 2009-2011 (2.58%, 44/1075). Compared with previous study, the sensitivity to cephalosporins and fusidic acid decreased to varying degrees, while that to chloramphenicol, ciprofloxacin, clindamycin, erythromycin, gentamicin, penicillin, and tetracycline increased significantly. The sensitivity to mupirocin, trimethoprim/sulfamethoxazole (TRISUL), and rifampicin still maintained at a high level (97.90%, 99.35% and 96.66% respectively). The leading multidrug resistance pattern of MRSA and methicillin-sensitive S. aureus (MSSA) were erythromycin-clindamycin-tetracycline (55.84%; 43/77) and erythromycin-clindamycin-chloramphenicol (27.85%, 44/158) respectively. 12 high-level mupirocin-resistant strains were detected, and notable differences in geographical distribution and seasonal variation were observed. The main types of MRSA were ST121 (46.08%, 94/204), followed by ST59 (19.61%, 40/204). SCCmec V (65.69%, 134/204) and SCCmec IV (31.86%, 65/204) were dominant epidemic types. ST121-V, ST59-IV, and ST22-V were the most prevalent clones nationwide. The detection rate of pvl had increased markedly from 9.09% (4/44) in 2009-2011 to 22.55% (46/204) in 2019-2021 (P

Abstract Eucommia ulmoides staminate flowers (EUF), a newly approved functional food in China, have great potential for hormonal regulation. Herein, we aim to demonstrate the chemical composition and pharmacological activity of EUF in testosterone production and hormonal regulation. EUF extract and its components, kaempferol and geniposidic acid, exhibited a strong stimulating effect by increasing testosterone secretion, reducing ROS production, or promoting viability in Leydig cells. Meanwhile, the increased testosterone production was related to the upregulation of mRNA and protein expression of the steroidogenic pathway, such as steroidogenic acute-regulatory protein (StAR), 3β -hydroxysteroid dehydrogenase type 1 (HSD3B1), 17α-hydroxylase/17,20-lyase (CYP17A1), and nuclear receptor subfamily 5 group A member 1 (NR5A1). However, PKA inhibitor H89 or adenylyl cyclase inhibitor SQ22536 could block their effect. The results of transgenic yeast models showed the androgenic agonistic effects of kaempferol and naringenin and the estrogenic agonistic effects of rutin. These results indicated that the testosterone promotional effect of EUF was related to the activation of the steroidogenic pathway and potential hormonal regulation. Kaempferol and geniposidic acid might be the key active ingredients.

Abstract Background There is little evidence about consistency between nasopharyngeal and pulmonary pathogens in children with severe pneumonia. This study aims to compare the difference of pathogens between nasopharyngeal aspirates (NPAs) collected before bronchoscopy and bronchoalveolar lavage fluids (BALFs) in children with severe community-acquired pneumonia (SCAP). Methods NPAs and BALFs were collected form pediatric SCAP cases hospitalized from January 2018 to March 2019. NPAs were colleced within 3 days before bronchoscopy. Samples were detected by direct immunofluorescence assay (DFA) for seven respiratory viruses and by routine bacterial culture in the clinical microbiology laboratory. Respiratory syncytial virus (RSV), Adenovirus (ADV), Influenza virus types A, B (IV-A and IV-B), Parainfluenza virus 1–3 (PIV1-3) were detected with a commercial assay. The virological and bacteriological detention results of NPAs were compared with the results of BALFs. Results In total 204 cases with mean age of 3.4 ± 2.8 years (IQR, 1 month-14 years) were included in the study. Both NPA and BALF were collected from those cases. The positive rates of pathogen in NPAs and BALFs were 25.0% (51/204) and 36.7% (75/204), respectively (x2 = 6.614, P = 0.010). Respiratory viruses were found in 16.1% (33/204) from NPAs and 32.3% (66/204) from BALFs (x2 = 14.524, P

ABSTRACT: Lactococcus lactis, a lactic acid bacterium, has been widely used in the fermented dairy products. The acid tolerance of L. lactis is of great importance to food fermentation and probiotic applications. As the first barrier of bacteria, the cell wall has a protective effect on strains under many stress conditions, whereas the regulatory mechanism has rarely been reported. Here, based on the transcription analysis of 9 cell wall or membrane-related genes of L. lactis F44 under acid stress, the transcription levels of DACB, DLTD, YLBA, HRTA, WP_080613266.1 (1610), and ERFK genes were significantly increased. We constructed 9 overexpressing strains with the cell wall or membrane-related genes, respectively. It was demonstrated that the survival rates under acid stress of DACB, DLTD, and ERFK were significantly higher than that of wild-type F44. To investigate the regulatory mechanism, a DNA pull-down assay was used to identify the transcriptional regulators of these 3 genes. It was discovered that the 2-component system (TCS) transcriptional regulator TCSR7 bound to the upstream region of DLTD involved in the teichoic acid (TA) alanylation. The combination was confirmed through an electrophoretic mobility shift assay in vitro. Reverse-transcription quantitative PCR results indicated that TCSR7 upregulated the expression of DLTD gene. In addition, the transcription level of TCSR7 increased approximately 1.8-fold (log2 fold change) under acidic conditions. In summary, this study found that TCSR7 was induced by acid stress to upregulate the transcription level of the DLT operon genes, which might increase the positive charge on the cell membrane surface to increase the acid tolerance of the strain. This study lays the foundation for the regulatory mechanism of TA alanylation under acid stress.

Thermoacidophilic type III pullulan hydrolase TK-PUL can completely hydrolyze starch to starch sugar under liquefaction condition. It has great application potential in the ''one step liquefaction-saccharification'' starch syrup production process. In this study, error-prone PCR technology was used to improve the catalytic activity of TK-PUL. After two sequential error-prone PCR and high-throughput screening, the mutant L538D with improved catalytic activity was obtained. Compared with TK-PUL, the specific activity of L538D with soluble starch as substrate increased by 50%, the specific activity of L538D toward pullulan increased by 21%. And the kcat/Km value of L538D for soluble starch, pullulan increased by 44% and 27%, respectively. In other words, the hydrolytic activity of L538D toward α-1,4-glycosidic bond and α-1,6-glycosidic bond were significantly improved, and the hydrolytic activity of L538D toward α-1,4-glycosidic bond increased to a greater degree. Homology modeling showed that replacing Leu538 with Asp in TK-PUL may improve the flexibility of the loop structure including the catalytic site Glu538 by shortening the length of the side chain of amino acid residues and reducing the hydrophobicity of amino acid residues, thus improving the catalytic activity of the enzyme. The results demonstrated that Leu538 in TK-PUL is vital for its catalytic activity.

Acute promyelocyte leukaemia (APL) is a subgroup of acute myeloid leukaemia. Dysregulation of clock genes has been revealed to be involved in APL progression. Herein, the mechanism of clock gene aryl hydrocarbon receptor nuclear translocator- like (ARNTL) in APL was explored. The expression of ARNTL, period circadian regulator 1 and 2 (PER1 and PER2) in APL tissue samples and normal samples was analysed by bioinformatic analysis. Gene expression in APL cells was detected by reverse transcription quantitative polymerase chain reaction. Acute promyelocyte leukaemia cell viability and cell cycle progression were assessed by cell counting kit 8 (CCK-8) assays and flow cytometry analyses, respectively. The protein levels of ARNTL and cell cycle markers were examined by western blotting. Interaction between ARNTL and miR-320a/b was confirmed by luciferase reporter assays. Aryl hydrocarbon receptor nuclear translocator-like was overexpressed in marrow tissues of patients with acute myeloid leukaemia and predicted poor outcome. Aryl hydrocarbon receptor nuclear translocator-like knockdown inhibited APL cell viability and arrested APL cells in the G1 phase. Mechanically, ARNTL was targeted by miR-320a/b. Moreover, miR-320a/b upregulation promoted cell cycle arrest in the G1 phase and suppressed the viability of APL cells, and the impacts were reversed by ARNTL overexpression. In conclusion, miR-320a/b suppresses cell viability and leads to cell cycle arrest by suppressing ARNTL in APL.

Abstract Background Circular RNAs (CircRNAs) play critical roles in gene expression regulation and disease development. Understanding the regulation mechanism of CircRNAs formation can help reveal the role of CircRNAs in various biological processes mentioned above. Back-splicing is important for CircRNAs formation. Back-splicing sites prediction helps uncover the mysteries of CircRNAs formation. Several methods were proposed for back-splicing sites prediction or circRNA-realted prediction tasks. Model performance was constrained by poor feature learning and using ability. Results In this study, CircCNN was proposed to predict pre-mRNA back-splicing sites. Convolution neural network and batch normalization are the main parts of CircCNN. Experimental results on three datasets show that CircCNN outperforms other baseline models. Moreover, PPM (Position Probability Matrix) features extract by CircCNN were converted as motifs. Further analysis reveals that some of motifs found by CircCNN match known motifs involved in gene expression regulation, the distribution of motif and special short sequence is important for pre-mRNA back-splicing. Conclusions In general, the findings in this study provide a new direction for exploring CircRNA-related gene expression regulatory mechanism and identifying potential targets for complex malignant diseases. The datasets and source code of this study are freely available at: https://github.com/szhh521/CircCNN .

Abstract The water-soluble β-cyclodextrin–curcumin (CDC) is used in pharmaceutical applications and as a natural food colorant. The previous study revealed that curcumin potentially impacted the reproductive system. The present study investigated the possible roles of the CDC in testosterone secretion in Leydig cells and mice. Primary Leydig cells were treated with the CDC to determine their effect on cell proliferation, testosterone levels, the protein and mRNA expression of the transcription factor, and steroidogenic enzymes. Our data showed that CDC stimulated testosterone production via upregulating transcription factor steroidogenic factor-1 (NR5A1), cAMP-response element-binding protein (CREB), and steroidogenic enzymes steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage enzyme (CYP11A1), 17-alpha-hydroxylase/17,20-lyase (CYP17A1), 3β-/17β-hydroxysteroid dehydrogenase type 1 (3β/17β-HSD, HSD3b1/HSD17b1). CDC could significantly stimulate H89-suppressed StAR and CREB expression but not reverse melatonin-suppressed StAR expression. We further detected the hormonal activity with transgenic yeast, and CDC showed potential androgenic antagonistic activity. Meanwhile, we investigated its aphrodisiac effect on hydrocortisone-induced mice. Exposure to hydrocortisone decreased the mating ability, reproductive organs, and testosterone level and disrupted testicular histology. However, all of these effects were significantly improved by CDC treatment. In conclusion, these results indicated that mechanisms of CDC in stimulating testosterone production involve upregulating the cAMP-PKA pathway.

Abstract Fluorescent probes based on rhodamine skeleton are extensively used in biological imaging. However, the construction of ratiometric fluorescent probes based on the rhodamine skeleton without introducing additional fluorophores is still challenging. Herein, we propose an effective method to construct a rhodamine‐based ratiometric fluorescent probe through the regulation of electron cloud density. A ratiometric fluorescent probe RDQF‐RB‐NTR was successfully constructed for the detection of nitroreductase (NTR). RDQF‐RB‐NTR exhibits good sensitivity, high selectivity, and ratiometric response to NTR. Cell imaging experiments showed that RDQF‐RB‐NTR can rapidly and accurately detect the fluctuation of NTR in cells and difference of NTR levels between normal cells and cancer cells. In addition, RDQF‐RB‐NTR was successfully applied to the imaging of NTR in liver tissue slices, and we found that the level of NTR was upregulated in liver cirrhosis.

To develop a biocatalyst with high efficiency, stability and reusability for the degradation of organic pollutant acridine in wastewater, a novel biocatalyst named bienzyme-inorganic hybrid nanoflowers beads were successfully prepared in the present work, designated as biE-HNFs-beads. This bienzyme biocatalyst composed of bienzyme-inorganic hybrid nanoflowers and traditional beads carriers were characterized by SEM, TEM, FT-IR, XRD, and EPR. The biE-HNFs-beads showed better stability, recyclability and improved catalytic activity for acridine degradation than that of free bienzyme. Furthermore, biE-HNFs-beads could reduce the diffusion and decomposition of the intermediate H2O2 through the bienzyme cascade reactions, which not only improved the stability of the bienzyme, but also accelerated the degradation of acridine. Under optimized conditions, the degradation rate of acridine by biE-HNFs-beads could reach 99.9 %. The stability study indicated that the biE-HNFs-beads exhibited enhanced stability, reusability and storage stability. Besides, the bioconversion products analysis of acridine degraded by biE-HNFs-beads biocatalyst were identified by LC-MS, and the enzymatic degradation pathway of acridine was inferred for the first time.

Background: Acute lung injury (ALI) is a common clinical disease with high mortality. Rujin Jiedu powder (RJJD) has been clinically utilized for the treatment of ALI in China, but the active constituents in RJJD and its protective mechanisms against ALI are still unclear.Methodology: ALI mice were established by intraperitoneal injection of LPS to test the effectiveness of RJJD in treating ALI. Histopathologic analysis was used to assess the extent of lung injury. An MPO (myeloperoxidase) activity assay was used to evaluate neutrophil infiltration. Network pharmacology was used to explore the potential targets of RJJD against ALI. Immunohistochemistry and TUNEL staining were performed to detect apoptotic cells in lung tissues. RAW264.7 and BEAS-2B cells were used to explore the protective mechanisms of RJJD and its components on ALI in vitro. The inflammatory factors (TNF-α, IL-6, IL-1β and IL-18) in serum, BALF and cell supernatant were assayed using ELISA. Western blotting was performed to detect apoptosis-related markers in lung tissues and BEAS-2B cells.Results: RJJD ameliorated pathological injury and neutrophil infiltration in the lungs of ALI mice and decreased the levels of inflammatory factors in serum and BALF. Network pharmacology investigations suggested that RJJD treated ALI via regulating apoptotic signaling pathways, with AKT1 and CASP3 as crucial targets and PI3K-AKT signaling as the main pathway. Meanwhile, baicalein, daidzein, quercetin and luteolin were identified as key constituents in RJJD targeting on the above crucial targets. Experimental investigations showed that RJJD significantly upregulated the expression of p-PI3K, p-Akt and Bcl-2, downregulated the expression of Bax, caspase-3 and caspase-9 in ALI mice, and attenuated lung tissue apoptosis. Four active constituents in RJJD (baicalein, daidzein, quercetin and luteolin) inhibited the secretion of TNF-α and IL-6 in LPS-induced RAW264.7 cells. Among these components, daidzein and luteolin activated the PI3K-AKT pathway and downregulated the expression of apoptosis-related markers induced by LPS in BEAS-2B cells.Conclusion: RJJD alleviates the inflammatory storm and prevents apoptosis in the lungs of ALI mice. The mechanism of RJJD in treating ALI is related to the activation of PI3K-AKT signaling pathway. This study provides a scientific basis for the clinical application of RJJD.

HIV-1 infection causes T cell dysfunction that cannot be fully restored by anti-retroviral therapy (ART). Myeloid-derived suppressor cells (MDSCs) expand and suppress T cell function during viral infection. In this study, we evaluated the dynamics of phenotypes and function of T cells and MDSCs and the effects of their interaction on CD4+ T cell reconstitution in people with acute HIV-1 infection (PWAH) with early ART. Flow cytometry was used to detect the phenotypic dynamics and function of T cells and MDSCs at pre-ART, 4, 24, 48, and 96 weeks of ART. We observed that T cells were hyper-activated and hyper-proliferative in PWAH at pre-ART. Early ART normalized T cell activation but not their proliferation. T cell proliferation, enriched in PD-1+ T cells, was persisted and negatively associated with CD4+ T-cell counts after ART. Moreover, M-MDSCs frequency was increased and positively correlated with T cell proliferation after 96 weeks of ART. M-MDSCs persisted and inhibited T cell proliferation ex vivo, which could be partially reversed by PD-L1 blockade. Further, we found higher frequencies of proliferative CD4+ T cells and M-MDSCs in PWAH with lower CD4+ T cell numbers (600 cells/μL) after 96 weeks of ART. Our findings indicate that persistent T cell proliferation, MDSCs expansion, and their interaction may affect CD4+ T-cell recovery in PWAH with early ART.

To improve the tribological characteristics of materials employed in spatial mechanisms, there is a significant requirement to develop solid lubricating composites with superior performance. This study investigates the tribological characteristics of composites consisting of a nickel matrix combined with silver molybdate and barium molybdate. The experimental analysis focuses on evaluating the tribological behaviors of these composites from 25 °C to 800 °C. The findings indicate that the combined application of silver molybdate and barium molybdate resulted in enhanced self-lubricating properties of the composites, particularly at temperatures over 400 °C. The inclusion of both silver molybdate and barium molybdate in the composite resulted in the achievement of a low friction coefficient (0.34–0.5), as well as a wear rate ranging from 0.47 to 1.25 × 10−4 mm3 N−1m−1, within the temperature range of 400 to 800 °C. Furthermore, an analysis was conducted to examine the wear processes of the composites at various sliding temperatures. This analysis was based on the evaluation of the chemical composition and morphologies of the sliding surfaces, which were verified by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and Raman spectroscopy.

Leaching in cement-based materials and dissolution in rocks are important problems in civil engineering. In the past century, concrete damage caused by leaching have occurred worldwide. And, rock dissolution is usually the main cause of karst rock erosions. This paper provides a review of the causes, influencing factors, and effects on engineering properties of dissolution of rocks and leaching of cement-based materials. The applied experimental methods for leaching and dissolution have been sorted out and discussed. In situ field experiments can be used to study dissolution under natural conditions, while the laboratory experiments can effectively shorten the experiment time length (by changing pH, temperature, pressure or other factors that affect the leaching or dissolution) to quickly investigate the mechanism of dissolution and leaching. Micro tests including XRD, SEM, EDS, and other testing methods can obtain the changes in material properties and microstructures under leaching and dissolution. In addition, with the advances in technologies and updated instruments, more and more new testing methods are being used. The factors affecting the leaching and dissolution include environmental factors, materials, and solvent parameters. The mechanisms and deterioration processes of leaching and dissolution varies according to the types of material and the compositions.

Various endeavours into semantic web technologies and ontology engineering have been made within the organisation of cultural data, facilitating public access to digital assets. Although models for conceptualising objects have reached a certain level of maturity, only a few have delved into the tacit roles of individuals in the development of knowledge. Simultaneously, the field of cultural analytics demands practical methods for integrating diverse multilingual materials into a consistent data representation. In this context, our work addresses a human-centred perspective to construct a knowledge graph presenting historical Chinese kung fu masters, aptly named MA2KG (Martial Arts MAsters Knowledge Graph). The data workflow is built upon an established ontology model that describes traditional martial arts. It aggregates information from heterogeneous bilingual sources through direct connections and rule-based inference, incorporating data from English Wikidata and Chinese Baidu Baike and complemented with manual annotations. In addition, we describe our methodology and process in making the dataset available with scripts for reproducing similar agent-mediated contexts, data application and inspection cases are provided to discuss our findings and concerns regarding the use of linked open data strategies.

Extensive occurrence of rice sheath blight has been observed in China in recent years due to agricultural practices and climatic conditions, posing a serious threat to rice production. Assessing habitat suitability for rice sheath blight at a regional scale can provide important information for disease forecasting. In this context, the present study aims to propose a regional-scale habitat suitability evaluation method for rice sheath blight in Yangzhou city using multisource data, including remote sensing data, meteorological data, and disease survey data. By combining the epidemiological characteristics of the crop disease and the Relief-F algorithm, some habitat variables from key stages were selected. The maximum entropy (Maxent) and logistic regression models were adopted and compared in constructing the disease habitat suitability assessment model. The results from the Relief-F algorithm showed that some remote sensing variables in specific temporal phases are particularly crucial for evaluating disease habitat suitability, including the MODIS products of LAI (4–20 August), FPAR (9–25 June), NDVI (12–20 August), and LST (11–27 July). Based on these remote sensing variables and meteorological features, the Maxent model yielded better accuracy than the logistic regression model, with an area under the curve (AUC) value of 0.90, overall accuracy (OA) of 0.75, and a true skill statistics (TSS) value of 0.76. Indeed, the results of the habitat suitability assessment models were consistent with the actual distribution of the disease in the study area, suggesting promising predictive capability. Therefore, it is feasible to utilize remotely sensed and meteorological variables for assessing disease habitat suitability at a regional scale. The proposed method is expected to facilitate prevention and control practices for rice sheath blight disease.

Fucosylated glycosaminoglycans (FGs) derived from sea cucumbers exhibit potent intrinsic Xase (iXase) inhibition, anticoagulation, and antithrombosis. Plasma activated partial thromboplastin time (APTT), a widely used screening test worldwide, is crucial for evaluating anticoagulant efficacy. However, the applicability of these commercially available APTT reagents for assessing anticoagulation of FGs remains unreported. In this study, we investigated the disparity between ellagic acid and colloidal silica APTT reagents in evaluating anticoagulation of dHG-5 and dHLFG-4, two depolymerized FGs, and elucidated the underlying rationale. The results demonstrated that dHG-5 and dHLFG-4 exhibited heightened sensitivity to the ellagic acid APTT reagent both in vitro and in vivo, and did not significantly affect the activation of APTT reagents for plasma. In addition, both ellagic acid and colloidal silica APTT reagents inhibited the anti-iXase of dHG-5 and dHLFG-4, and the inhibition of the ellagic acid APTT reagent was less pronounced compared to the colloidal silica APTT reagent. These findings suggest that the reduced impact of the ellagic acid APTT reagent on the anti-iXase activity of dHG-5 and dHLFG-4 is responsible for the increased sensitivity in plasma APTT analysis. This study offers valuable insights into the characteristics of two APTT reagents applied for assessing the anticoagulant activity of FG-related compounds.

Sesquiterpenes are a type of abundant natural product with widespread applications in several industries. They are biosynthesized by sesquiterpene synthases (STSs). As valuable and abundant biological resources, mushroom-forming fungi are rich in new sesquiterpenes and STSs, which remain largely unexploited. In the present study, we collected information on 172 STSs from mushroom-forming fungi with experimentally characterized products from the literature and sorted them to develop a dataset. Furthermore, we analyzed and discussed the phylogenetic tree, catalytic products, and conserved motifs of STSs. Phylogenetic analysis revealed that the STSs were clustered into four clades. Furthermore, their cyclization reaction mechanism was divided into four corresponding categories. This database was used to predict 12 putative STS genes from the edible fungi Flammulina velutipes. Finally, three FvSTSs were selected to experimentally characterize their functions. FvSTS03 predominantly produced Δ-cadinol and FvSTS08 synthesized β-barbatene as the main product; these findings were consistent with those of the functional prediction analysis. A product titer of 78.8 mg/L β-barbatene was achieved in Saccharomyces cerevisiae via metabolic engineering. Our study findings will help screen or design STSs from fungi with specific product profiles as functional elements for applications in synthetic biology.

The convection initiation (CI) mechanisms of severe storms have received increasing attention because severe storms have been occurring more frequently around the globe in recent years. In this work, the CI mechanisms of severe convective weather associated with a gust front (GF) which occurred on 9 July 2016, near the Korla at the northern edge of the Tarim Basin, Xinjiang, is investigated using observational data including Doppler weather radar data and automatic weather stations data, and high-resolution numerical simulation data. The results showed that, during the eastward movement of the GF, a number of convective cells were successively triggered in the vicinity of the GF, which developed rapidly and continuously merged with the convective system from behind, resulting in the further development and maintenance of this convective system. According to the diagnostic analysis of vertical acceleration which can be decomposed into dynamic acceleration (ad) and buoyant acceleration (ab), it was found that both ad (up to ~4 × 10−3 m s−2) and ab (up to ~7 × 10−3 m s−2) made positive contributions to the CI. Further analyses based on the decompositions of the ad and ab revealed that the extension term was the main contributor for the ad, while the warming of the dry air due to the release of latent heat from the precipitation condensate made the major contribution to the ab. The extension term indicates the elevated convergence jointly induced by the airflow of mid-level horizontal convective rolls (MHCRs) and updraft flow near the leading edge of the GF. The jointly induced elevated convergent updraft can be considered to be an important contributor for the CI mechanisms.

Abstract Background Previous studies have primarily implemented problem-based learning (PBL) or flipped classroom (FC) teaching models in different majors; however, research on the combined PBL-FC teaching method in clinical medicine is scarce. Therefore, we investigated the combined PBL-FC teaching method in teaching ocular trauma on students’ competencies. Method About 75 ophthalmology postgraduates were randomly divided into PBL-FC and traditional teaching groups. Students completed pre-and post-class theoretical examinations, skills evaluation, learning ability scales, and feedback questionnaires. Results Both groups showed significantly higher theoretical scores and improved learning ability. Feedback questionnaire scores of the PBL-FC group’s postgraduates without clinical experience were significantly higher than the traditional group’s for some items; there was no difference between groups in postgraduates with clinical experience. PBL-FC group’s pre-class preparation time was significantly longer than the traditional group’s, but the post-class review time was significantly shorter. PBL-FC group’s post-class theoretical performance was significantly higher than the traditional group’s. There was no statistical difference between the groups regarding skill operation. Among postgraduates without clinical experience, the PBL-FC group’s skill operation performance was significantly higher than the traditional group’s; for postgraduates with clinical experience, the traditional group’s skill operation performance was significantly higher than the PBL-FC group’s. Conclusions PBL-FC teaching is better for students without clinical experience or knowledge of ophthalmic diseases. Meanwhile, traditional teaching is a good choice for students with clinical experience who need more relevant knowledge.

Super-resolution microscopy is a powerful tool for cellular studies but requires bright and stable fluorescent probes. Here, the authors report on a strategy to introduce quinoxaline motifs to conventional probes to make them brighter, more photostable, larger Stokes shift, and demonstrate the probes for biosensing applications.

As global supply is still inadequate to address the worldwide requirements for HPV vaccines, we assessed the safety and immunogenicity of a new bivalent HPV16/18 vaccine. In this randomized, double-blind, placebo-controlled, phase 2 trial, healthy 9–45-year-old Chinese females in three age cohorts (600 aged 9–17 years; 240 aged 18–26 years; 360 aged 27–45 years) were randomized 1:1 to receive three doses (0,2,6 months) of HPV16/18 vaccine or placebo. We measured neutralizing antibodies against HPV 16 and 18 at 7 months and monitored safety to 12 months in all age cohorts; 9–17-year-old girls were monitored for safety and immunogenicity to 48 months. In vaccinees, 99.8% seroconverted for HPV 16 and 18 types at 7 months; respective GMTs of 5827 (95% CI: 5249, 6468) and 4223 (3785, 4713) were significantly (p

The aircraft is subjected to high-temperature and high-pressure conditions during flight, which renders it susceptible to the occurrence of creep phenomenon. Several academics have conducted extensive research on this issue. This research paper provides a comprehensive overview of the existing literature on creep phenomena in aircraft engines. First, several classical creep calculation models are enumerated and categorized as creep life calculation, creep-fatigue life calculation, and creep deformation calculation. Studies on creep phenomena are conducted in various components of aircraft engines, such as the engine’s turbine blades, turbine disks, and combustion chambers. The creep behavior of turbine blades in aircraft engines has been extensively researched. Furthermore, the protective measures aimed at mitigating creep are presented. Materials with high creep resistance can be used, and alternative fuels could be implemented. This paper provides an in-depth analysis of the advantages of creep in aircraft, presented in a favorable perspective. Finally, the prospective future research direction is discussed.

ObjectiveThis study aims to analyze the serotype distribution and drug resistance of Streptococcus pneumoniae isolated from children aged 8 days to 7 years in Urumqi, China, between 2014 to 2021, during which PCV13 was introduced in the private sector’s immunization program and COVID-19 control was administrated in the last 2 years.MethodsSerotypes of S. pneumoniae isolates were determined by Quellung reaction, and their susceptibility against 14 antimicrobials were tested. According to the start year of PCV13 administration (2017) and COVID-19 control (2020), the study period was divided into three stages: 2014–2015, 2018–2019, and 2020–2021.ResultsA total of 317 isolates were involved in this study. The most common serotypes were type 19F (34.4%), followed by 19A (15.8%), 23F (11.7%), 6B (11.4%), and 6A(5.0%). The coverage rate of both PCV13 and PCV15 was 83.0%. The coverage of PCV20 was a little higher at 85.2%. The resistance rate against penicillin was 28.6% according to the breakpoints of oral penicillin, which would reach up to 91.8% based on the breakpoints of parenteral penicillin for meningitis. The resistance rates to erythromycin, clindamycin, tetracycline, and sulfamethoxazole-trimethoprim were 95.9%, 90.2%, 88.9%, and 78.8%, respectively. The PCV13 isolate was more resistant to penicillin than the non-PCV13 ones. There was not any significant change found in the serotype distribution since the PCV13 introduction and the COVID-19 control. The resistance rate against oral penicillin slightly elevated to 34.5% in 2018–2019 from 30.7% in 2014–2015 and then decreased significantly to 18.1% in 2020–2021 (χ2 = 7.716, P < 0.05), while the resistance rate to ceftriaxone (non-meningitis) continuously declined from 16.0% in 2014–2015 to 1.4% in 2018–2019 and 0% in 2020–2021 (Fisher = 24.463, P < 0.01).ConclusionThe common serotypes of S. pneumoniae isolated from children in Urumqi were types 19F, 19A, 23F, 6B, and 6A, which we found to have no marked change since the PCV13 introduction and the COVID-19 control However, the resistance rate to oral penicillin and ceftriaxone significantly declined in the COVID-19 control stage.

Due to the gradual depletion of shallow mineral resources at present, mines are now gradually entering the deep mining stage. To promote the safe and efficient green mining of deep coal resources and sustainable energy development, and to improve the production efficiency of paste filling mining, the research group has performed this study on the green filling mining technology and application of the working face. Taking working face 1241 (3) of the Xieqiao coal mine as the engineering background, the selection and experiment of filling materials were carried out, and the gangue, fly ash and cement produced by the Xieqiao coal mine were used as the filling aggregate. Next, the strength changes before and after paste filling was obtained by theoretical calculation. The strength at the early stage of filling was no less than 0.13 MPa, and that at the late stage of filling was no less than 2 MPa. Based on previous experimental research and theoretical calculation, the mixing pumping process of paste material ratio and the gangue crushing process were determined, and the filling pipeline system was designed. Then, based on the traditional coal mining technology, a filling mining technology of working face was designed and optimized. The field application of the research results shows that after the goaf of the working face had been filled, the ground pressure behavior of the coal wall of the working face was significantly weakened, and the stability of the surrounding rock of the working face was effectively controlled. Therefore, the method achieved good results, effectively controlled the stability of surrounding rock in goaf, and provided a theoretical basis and data support for realizing safe, efficient and green mining of deep coal resources. The results of this study bear important significance and application value.

Systemic lupus erythematosus (SLE) is a common multisystem, multiorgan heterozygous autoimmune disease. The main pathological features of the disease are autoantibody production and immune complex deposition. Autophagy is an important mechanism to maintain cell homeostasis. Autophagy functional abnormalities lead to the accumulation of apoptosis and induce the autoantibodies that result in immune disorders. Therefore, improving autophagy may alleviate the development of SLE. For SLE, glucocorticoids or immunosuppressive agents are commonly used in clinical treatment, but long-term use of these drugs causes serious side effects in humans. Immunosuppressive agents are expensive. Traditional Chinese medicines (TCMs) are widely used for immune diseases due to their low toxicity and few side effects. Many recent studies found that TCM and its active ingredients affected the pathological development of SLE by regulating autophagy. This article explains how autophagy interferes with immune system homeostasis and participates in the occurrence and development of SLE. It also summarizes several studies on TCM-regulated autophagy intervention in SLE to generate new ideas for basic research, the development of novel medications, and the clinical treatment of SLE.

IntroductionSix species of alfalfa commonly found in northern China were collected in the present study.MethodsThe chemical composition and epiphytic microbial communities during the ensiling were analyzed; and their effects on fermentation quality and silage bacterial communities were assessed. The effects of physicochemical characteristics of alfalfa on the bacterial community were also investigated in terms of nutritional sources of microbial growth and reproduction.Results and discussionThe results showed that the chemical composition was significantly different in various alfalfa varieties, yet, the dominant genera attached to each variety of alfalfa was similar, except for pantoea (p

Abstract Background With an increase in the diagnosis of plastic bronchitis (PB) cases, to enhance paediatricians’ knowledge and add to the few existing studies, we explored the clinical characteristics, diagnosis, and treatment of PB in children. Methods The clinicopathological data of 43 children admitted to the Xiamen Children’s Hospital and the Women and Children’s Hospital, affiliated to the Xiamen University from December 2016 to December 2019, were retrospectively analysed. Results All the children had cough, with 41 of them having associated fever. A peak temperature > 40 ℃ was observed in 25 children. Twenty-six children had shortness of breath, 27 had reduced respiratory sounds on the affected side, and 35 had audible moist rales on the affected side. Lactate dehydrogenase in all children increased to different degrees, and 29 had elevated D-dimer and fibrinogen degradation products. Lung imaging showed pulmonary consolidation and atelectasis, mainly in the bilateral lower lung lobes, in all the children. However, 31 had pleural effusion, mainly a small parapneumonic effusion. The infections were mainly caused by adenovirus and Mycoplasma pneumoniae. The casts in all 43 children were sucked or clamped out under bronchoscopy, and 10 were found to have type I PB on pathological examination. All children were treated with anti-infective therapy in addition to bronchoscopic cast removal. Thirty-one children were treated with methylprednisolone, and 16 with gamma globulin. Except for one child who was non-adherent to treatment, all other children showed improvement, or were cured and discharged from the hospital. Follow-up lung imaging at 3 months revealed that the lungs were fully re-expanded in 40 children. At the 6-month follow-up, six children had small airway lesions, four had obliterative bronchiolitis, and one had bronchiectasis. Conclusions Paediatric PB often occurs secondary to respiratory tract infections and progresses rapidly, with hyperpyrexia, cough, and shortness of breath as the main clinical manifestations. Pulmonary consolidation, atelectasis, and pleural effusion are seen on lung imaging, and early bronchoscopy and removal of casts in the trachea and bronchi are effective treatment options.

Abstract Background Growing evidence suggests an association between Parkinson’s disease (PD) and diabetes mellitus (DM). At the cellular level, long-term elevated levels of glucose have been shown to lead to nigrostriatal degeneration in PD models. However, the underlying mechanism is still unclear. Previously, we have elucidated the potential of type 2 diabetes mellitus (T2DM) in facilitating PD progression, involving aggregation of both alpha-synuclein (α-syn) and islet amyloid polypeptide in the pancreatic and brain tissues. However, due to the complicated effect of insulin resistance on PD onset, the actual mechanism of hyperglycemia-induced dopaminergic degeneration remains unknown. Methods We employed the type 1 diabetes mellitus (T1DM) model induced by streptozotocin (STZ) injection in a transgenic mouse line (BAC-α-syn-GFP) overexpressing human α-syn, to investigate the direct effect of elevated blood glucose on nigrostriatal degeneration. Results STZ treatment induced more severe pathological alterations in the pancreatic islets and T1DM symptoms in α-syn-overexpressing mice than in wild-type mice, at one month and three months after STZ injections. Behavioral tests evaluating motor performance confirmed the nigrostriatal degeneration. Furthermore, there was a marked decrease in dopaminergic profiles and an increase of α-syn accumulation and Serine 129 (S129) phosphorylation in STZ-treated α-syn mice compared with the vehicle-treated mice. In addition, more severe neuroinflammation was observed in the brains of the STZ-treated α-syn mice. Conclusion Our results solidify the potential link between DM and PD, providing insights into how hyperglycemia induces nigrostriatal degeneration and contributes to pathogenic mechanisms in PD.

Abstract Background Lung ultrasound (LUS) is a useful tool for assessing the severity of lung disease, without radiation exposure. However, there is little data on the practicality of LUS in assessing the severity of bronchopulmonary dysplasia (BPD) and evaluating short-term clinical outcomes. We adapted a LUS score to evaluate BPD severity and assess the reliability of mLUS score correlated with short-term clinical outcomes. Methods Prospective diagnostic accuracy study was designed to enroll preterm infants with gestational age

This article investigates the optimal sliding mode control approach for consensus of nonlinear discrete-time high-order multi-agent systems (MASs). First, the nonlinearity and communication delay in the MAS is solved by designing a distributed discrete-time integral sliding mode control law, together with a proof of reachability of the sliding mode surface, as well as a proof that the chattering of the system is attenuated. In addition, the optimal controller is designed based on the model obtained after the distributed sliding mode control law is applied to the system. The merits of the proposed distributed sliding mode controller with the fusion of optimal control are that it can reduce the chattering of the MASs and their existence of quasi-sliding modes, as well as tolerate the negative impact caused by communication delay among agents. The MASs can achieve consensus quickly with the combined action of the sliding mode controller and the optimal controller. Finally, two examples are given to verify the effectiveness of the control method proposed in this paper.

Endometrial cancer (EC) is one of the three fatal tumors of the female reproductive system. Epigenetic alterations have been reported to be important in tumorigenesis, especially the chromatin accessibility changes and transcription factor binding differences. However, the regulatory mechanism underlying epigenetic alterations in EC development remains unclear. Here, we identified and characterized transcription factor binding site clustered regions (TFCRs) by integrating chromatin accessibility and transcription factor binding information. We totally identified 78,820 TFCRs and explored the relationship between TFCRs and regulatory elements, gene expression and mutation. Finally, we constructed a bioinformatic framework to identify candidate oncogenes and screened 13 candidate key genes, which may serve as potential diagnostic markers or therapeutic targets of EC.

In recent years, aluminum alloy has been increasingly used in building structures, becoming an important construction material for metal structures. Currently, aluminum alloy is commonly used in buildings as beam–column components, profiled roof panels, and door and window frames, among other forms. However, there is limited research on the mechanical properties of aluminum alloy roof panels with irregular curved surfaces. In this study, a full-scale curved double-layer anisotropic riveted aluminum alloy roof panel was subjected to a load test to analyze its deformation patterns and failure mechanisms. The results indicate that the load-bearing capacity of the roof panel meets the design requirements. During failure, neither the upper nor lower layers of the panel enter the plastic deformation stage, indicating sufficient safety redundancy. The failure mode observed is a ductile failure with noticeable deformation with the weak points of the component being the riveted connections of the stiffeners. A finite element model was established for numerical simulation and the results matched well with the experimental data. Finally, a theoretical calculation for the ultimate load-bearing capacity of the roof panel was derived, providing a reference for design purposes.

As resources provided by single unmanned aerial vehicles (UAVs) are limited, we propose a cross-platform UAV swarm key management scheme for task scenarios in denied environments. In denied environments where the communication link is open and the UAV nodes may go invalid, secure communication is often at stake. To solve this problem, we propose a key management scheme which, based on the Chinese remainder theorem (CRT) and the Hash function, constructs a swarm key by combining the local key and the session key to reduce the overhead of individual UAV nodes in the swarm. Meanwhile, the swarm head node constructs broadcast messages according to the key update needs, which reduces the overhead of the member nodes, improves the efficiency of key updating, and fulfills the key establishment and updating of the UAV swarm. Experiments show that our proposed scheme has forward and backward security and can defend against collusion attacks and replay attacks; our method was compared with other methods on the MIRACL cryptographic library in Visual Studio 2019, and it was found that our method has a lower computing and communication overhead, provides a solution to cross-platform key management of UAV swarms in denied environments, and ensures safe communication of UAVs in the swarm.