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Abstract Background This study aimed to investigate whether persistent human papillomavirus integration at the same loci (PHISL) before and after treatment can predict recurrent/residual disease in women with CIN2-3. Methods A total of 151 CIN2-3 women treated with conization between August 2020 and September 2021 were included. To investigate the precision of HPV integration, we further analyzed HPV integration-positive patients. Sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively), and the Youden index for predicting recurrence/residual disease were calculated. Results Among the 151 enrolled CIN2-3 women, 56 were HPV integration-positive and 95 had HPV integration-negative results. Six (10.7%) experienced recurrence among 56 HPV integration-positive patients, which was more than those in HPV integration-negative patients (one patient, 1.1%). In the 56 HPV integration-positive patients, 12 had positive HPV results after treatment, seven had PHISL, and two had positive cone margin. Among the seven patients who tested with PHISL, six (85.7%) had residual/recurrent disease. PHISL was a prominent predictor of persistent/recurrent disease. The HPV test, the HPV integration test, and PHISL all had a sensitivity of 100% and a NPV of 100% for residual/recurrent disease. PHISL showed better specificity (98.0% vs. 82.0%, p = 0.005) and PPV (85.7% vs. 40.0%, p = 0.001) than the HPV test for predicting recurrence. Conclusions The HPV-integration-positive CIN2-3 women had much higher relapse rates than HPV-integration-negative CIN2-3 women. The findings indicate that PHISL derived from preoperative and postoperative HPV integration tests may be a precise biomarker for the identification of residual/recurrent CIN 2/3.

Air pollution is a global issue that threatens human health. In recent years, more and more studies have found that air pollution is closely related to the occurrence of depression. As a serious neuropsychiatric disorder whose incidence is rising rapidly year by year, depression has become an invisible killer of public health. At present, studies on the correlation between air pollution and depression are still very limited, and the underlying molecular mechanisms by which air pollution affects depression are not clear. Based on existing epidemiological and toxicological studies, this paper provided a review of the relationship between air pollution and depression and the possible biological mechanisms, with a focus on the relationship between air pollution and depression indicators and the possible factors affecting depression such as types of air pollutants, exposure time, age and health status of study subjects. In addition, the potential roles of neuroinflammation, oxidative stress, neurogenesis, and apoptosis in the process of air pollution-induced depression were also discussed in order to provide a scientific basis for the prevention and treatment of air pollution-induced depression.

Immune nutrition, as an integral component of nutritional support therapy, has garnered significant attention and research in the treatment of gastrointestinal malignancies. Recent advancements in nutritional formulas containing components such as glutamine, omega-3 polyunsaturated fatty acids, and arginine have led to the development of what is now termed immune nutrition or pharmacological nutrition. These formulations go beyond traditional nutritional support, functioning more like nutritional supplements with pharmacological effects. Patients with gastrointestinal malignancies often experience malnutrition and metabolic disturbances, resulting in immune dysfunction, cytokine dysregulation, and endocrine abnormalities. These issues can compromise intestinal mucosal barrier function, affecting the efficacy and prognosis of anticancer therapies. Recent studies indicate that immune nutrition can modulate specific mechanisms involved in various immune and inflammatory pathways, thereby improving patients’ immune status and treatment outcomes. While optimal patient selection, dosing, and timing of immune nutrition are still under investigation, its potential applications in oncology are promising. This article aims to analyze the existing evidence regarding the therapeutic benefits of immune nutrition in gastrointestinal malignancies, offering insights into its clinical standardization and application.

Abstract Convolutional neural networks (CNNs) have been the dominant architectures for feature extraction tasks, but CNNs do not look for and focus on some specific image features. Correlation operations play an important role in visual tracking. However, the correlation operation reserves a large amount of unfavorable background information. In this paper, we propose an effective feature recognizer including channel and spatial attention modules to focus on important object feature information. Thus, the representation power of the feature extraction network is improved. Further, we design a multi-scale feature fusion network. The fusion network performs feature fusion on template feature and encoded feature branches to establish connections between features at different scales. Experiments on six benchmarks demonstrate that the proposed tracker outperforms the state-of-the-art trackers. In particular, the proposed tracker achieves an 80.4% AUC on TrackingNet and a 68.4% AUC on GOT-10k while running at a real-time speed.

Abstract Background Cervical cancer (CC) causes more than 311,000 deaths annually worldwide. The integration of human papillomavirus (HPV) is a crucial genetic event that contributes to cervical carcinogenesis. Despite HPV DNA integration is known to disrupt the genomic architecture of both the host and viral genomes in CC, the complexity of this process remains largely unexplored. Results In this study, we conducted whole-genome sequencing (WGS) at 55-65X coverage utilizing the PacBio long-read sequencing platform in SiHa and HeLa cells, followed by comprehensive analyses of the sequence data to elucidate the complexity of HPV integration. Firstly, our results demonstrated that PacBio long-read sequencing effectively identifies HPV integration breakpoints with comparable accuracy to targeted-capture Next-generation sequencing (NGS) methods. Secondly, we constructed detailed models of complex integrated genome structures that included both the HPV genome and nearby regions of the human genome by utilizing PacBio long-read WGS. Thirdly, our sequencing results revealed the occurrence of a wide variety of genome-wide structural variations (SVs) in SiHa and HeLa cells. Additionally, our analysis further revealed a potential correlation between changes in gene expression levels and SVs on chromosome 13 in the genome of SiHa cells. Conclusions Using PacBio long-read sequencing, we have successfully constructed complex models illustrating HPV integrated genome structures in SiHa and HeLa cells. This accomplishment serves as a compelling demonstration of the valuable capabilities of long-read sequencing in detecting and characterizing HPV genomic integration structures within human cells. Furthermore, these findings offer critical insights into the complex process of HPV16 and HPV18 integration and their potential contribution to the development of cervical cancer.

Abstract Tumor-infiltrating T cells recognize, attack, and clear tumor cells, playing a central role in antitumor immune response. However, certain immune cells can impair this response and help tumor immune escape. Therefore, exploring the factors that influence T-cell infiltration is crucial to understand tumor immunity and improve therapeutic effect of cancer immunotherapy. The use of single-cell RNA sequencing (scRNA-seq) allows the high-resolution analysis of the precise composition of immune cells with different phenotypes and other microenvironmental factors, including non-immune stromal cells and the related molecules in the tumor microenvironment of various cancer types. In this review, we summarized the research progress on T-cell infiltration and the crosstalk of other stromal cells and cytokines during T-cell infiltration using scRNA-seq to provide insights into the mechanisms regulating T-cell infiltration and contribute new perspectives on tumor immunotherapy.

The conflict between multiple functions of human use and habitat conservation represents an intractable challenge for environmental management. While numerous studies on marine conservation prioritize cumulative impact assessments (CIA) to tackle this issue, estuaries — despite their immense conservation significance amidst intense human activities — remain overlooked. Taking the Yangtze River Estuary (YRE) as the case study area, it is one of the most intensely human-utilized estuaries globally, yet it serves as a critical habitat and migratory corridor for the endangered Chinese sturgeon (Acipenser sinensis).We employed ecological indicators and quantitative modeling to assess habitat suitability and cumulative anthropogenic impacts on this endangered species in the YRE. The results demonstrated that suitable habitat distribution and human impact varied for juvenile Chinese sturgeon in the YRE. The suitable habitat distribution for juvenile Chinese sturgeon was concentrated in Chongming Dongtan and the North Channel. Ship density, submarine optical cables, and smooth cord grass invasion were the main anthropogenic factors impacting the Chinese sturgeon's migrating habitat in the YRE. Moreover, existing Chinese sturgeon habitats remain at risk, with 36.24 % of potential habitats and 56.60 % of high human impact areas requiring enhanced protection. Adaptive management strategies were proposed, tailored to the spatial and environmental protection needs across the dynamic habitat demands of aquatic species. Our spatially explicit and indicator-based findings provide key scientific support for enlarging protected areas and implementing adaptive management of human activities to balance conservation and sustainable use in this highly utilized ecosystem.

Abstract CAR T cell therapy has been successfully used in the treatment of hematological malignancies, and the strategy that deletion of inhibitory receptor on the CAR T cell surface, such as PD-1, greatly enhance the antitumor effects. Here, we describe a one-step electroporation for the co-transfection of Cas9:sgRNA and CAR plasmids on primary T cells to demonstrate the effect of SHP-1 deletion in CAR T cells. By using PiggyBac Transposase system, we can achieve more than 90% of T cells express CAR gene and nearly 60% SHP-1 knockout efficiency in T cells. We show that knockout of SHP-1 in CD133 CAR T cells resulted in significantly improve the cytolysis effect on CD133 positive glioma cell lines. We further demonstrate that the enhanced antitumor efficacy of SHP-1 deletion is due to the increased release of TNF-α, IL-2 and IFN-γ in vitro. Finally, we evaluated the biosafety of Cas9 genome editing and did not find any insertions of Cas9 and obvious editing in off-target sites in CAR T cells. These data provide an approach for achieving both intracellular inhibitory molecule, SHP-1 deletion and CD133 CAR gene over-expression in human T cells. And SHP-1 could be a new potential target for adoptive CAR T cells immunotherapy.

The floatability of fluorite and calcite exhibit similar properties, rendering their flotation separation challenging. Macromolecular polysaccharide reagents containing the polyhydroxyl group have shown broad promising application. The selectivity of polysaccharide is relatively low. In this study, the introduction of Fe3+ was employed to enhance the selective adsorption capacity of Pullulan polysaccharide towards fluorite and calcite minerals, thereby achieving effective flotation separation. Furthermore, the mechanism underlying intramolecular interactions was elucidated. The DFT calculation and XPS analysis revealed that the adsorption of Fe3+ on the calcite surface was more favorable, leading to the formation of a Ca-O-Fe structure. The MD simulation, XPS analysis, and Zeta potential analysis revealed that the Fe-OH groups on the surface of calcite reacted with the -OH groups in Pullulan and formed bonds, resulting in the formation of a Calcite-Fe-Pullulan structure. This facilitated the attachment of a significant number of Pullulan molecules to the calcite surface. The formation of a hydrophilic layer on the outer surface of calcite by Pullulan, in contrast to the absence of such layer on fluorite’s surface, results in an increased disparity in surface floatability between these two minerals, thereby enhancing the efficiency of flotation separation.

Neuroinflammation has been identified as another significant pathogenic factor in Alzheimer’s disease following Aβ amyloid deposition and tau protein hyperphosphorylation, activated in the central nervous system by glial cells in response to injury-related and pathogen-related molecular patterns. Moderate glial cell activity can be neuroprotective; however, excessive glial cell activation advances the pathology of Alzheimer’s disease and is accompanied by structural changes in the brain interface, with peripheral immune cells entering the brain through the blood-brain barrier, creating a vicious circle. The immunomodulatory properties of mesenchymal stem cells (MSCs) are primarily conveyed through extracellular vesicles (EVs). MSC-EVs participate in chronic inflammatory and immune processes by transferring nucleic acids, proteins and lipids from the parent cell to the recipient cell, thus MSC-EVs retain their immunomodulatory capacity while avoiding the safety issues associated with living cell therapy, making them a promising focus for immunomodulatory therapy. In this review, we discuss the modulatory effects of MSC-EVs on Alzheimer’s disease-associated immune cells and the mechanisms involved in their treatment of the condition. We have found a clinical trial of MSC-EVs in Alzheimer’s disease treatment and outlined the challenges of this approach. Overall, MSC-EVs have the potential to provide a safe and effective treatment option for Alzheimer’s disease by targeting neuroinflammation.

Choosing a suitable bioaerosol sampler for atmospheric microbial monitoring has been a challenge to researchers interested in environmental microbiology, especially during a pandemic. However, a comprehensive and integrated evaluation method to fully assess bioaerosol sampler performance is still lacking. Herein, we constructed a customized wind tunnel operated at 2–20 km/h wind speed to systematically and efficiently evaluate the performance of six frequently used samplers, where various aerosols, including Arizona test dust, bacterial spores, gram-positive and gram-negative bacteria, phages, and viruses, were generated. After 10 or 60 min of sampling, the physical and biological sampling efficiency and short or long-term sampling capabilities were determined by performing aerodynamic particle size analysis, live microbial culturing, and a qPCR assay. The results showed that AGI-30 and BioSampler impingers have good physical and biological sampling efficiencies for short-term sampling. However, their ability to capture aerosols at low concentrations is restricted. SASS 2300 and BSA-350 wet-wall cyclones had excellent enrichment ratios and high microbial cultivability in both short-term and long-term sampling; however, they were not suitable for quantitative studies of aerosols. Polycarbonate filter samplers showed outstanding performance in physical and long-term sampling but lacked the ability to maintain microbial activity, which can be improved by gelatin filter samplers. However, limitations remain for some fragile microorganisms, such as E. coli phage PhiX174 and coronavirus GX_P2V. In addition, the effects of wind speed and direction should be considered when sampling particles larger than 4 µm. This study provides an improved strategy and guidance for the characterization and selection of a bioaerosol sampler for better measurement and interpretation of collected ambient bioaerosols.

Abstract Siamese-based trackers have been widely studied for their high accuracy and speed. Both the feature extraction and feature fusion are two important components in Siamese-based trackers. Siamese-based trackers obtain fine local features by traditional convolution. However, some important channel information and global information are lost when enhancing local features. In the feature fusion process, cross-correlation-based feature fusion between the template and search region feature ignores the global spatial context information and does not make the best of the spatial information. In this paper, to solve the above problem, we design a novel feature extraction sub-network based on batch-free normalization re-parameterization convolution, which scales the features in the channel dimension and increases the receptive field. Richer channel information is obtained and powerful target features are extracted for the feature fusion. Furthermore, we learn a feature fusion network (FFN) based on feature filter. The FFN fuses the template and search region features in a global spatial context to obtain high-quality fused features by enhancing important features and filtering redundant features. By jointly learning the proposed feature extraction sub-network and FFN, the local and global information are fully exploited. Then, we propose a novel tracking algorithm based on the designed feature extraction sub-network and FFN with re-parameterization convolution and feature filter, referred to as RCFT. We evaluate the proposed RCFT tracker and some recent state-of-the-art (SOTA) trackers on OTB100, VOT2018, LaSOT, GOT-10k, UAV123 and the visual-thermal dataset VOT-RGBT2019 datasets, which achieves superior tracking performance with 45 FPS tracking speed.

The coronavirus disease 2019 (COVID-19) pandemic caused by frequently mutating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a worldwide impact. However, detailed data on the potential aerosol transmission of SARS-CoV-2 in real-world and controlled laboratory settings remain sparse. During the COVID-19 pandemic in Shanghai, China in 2022, samples were collected in a Fangcang shelter hospital, a large-scale temporary hospital rapidly built by converting the existing National Exhibition and Convention Center (Shanghai) into a health care facility. Aerosol samples at different sites and intervals around patients and in public areas, surface samples, and pharyngeal swab samples from corresponding patients were included. Samples were tested for SARS-CoV-2 using real-time quantitative polymerase chain reaction (RT-qPCR) assays, followed by sequencing if the cycle threshold (Ct) value was < 30. The positivity rate for SARS-CoV-2 in aerosol samples was high in contaminated zones (37.5%, 104/277), especially around the bed (41.2%, 68/165) and near ventilation inlets (45.2%, 14/31). The prevalence of SARS-CoV-2 around the bed, public areas, and air inlets of exhaust vents fluctuated and was closely related to the positivity rate among patients at corresponding sampling sites. Some surface samples of different personal protective equipment from medical staff had high positivity rates. Sixty sequences of joined ORF1ab and spike genes obtained from sixty samples represented two main clusters of Omicron SARS-CoV-2. There was consistency in virus sequences from the same patient and their environment, and the detected virus sequences matched those of virus strains in circulation during the collection periods, which indicated a high likelihood of cross-contamination in the Fangcang shelter hospital. In summary, the results provide a quantitative and real landscape of the aerosol transmission of SARS-CoV-2 and a patient-centered view of contamination in large and enclosed spaces and offer a useful guide for taking targeted measures to avoid nosocomial infections during the management of SARS-CoV-2 or other respiratory virus diseases in a Fangcang shelter hospital.

Abstract. Esophageal cancer (EC) is one of the most common aggressive malignant tumors in the digestive system with a severe epidemiological situation and poor prognosis. The early diagnostic rate of EC is low, and most EC patients are diagnosed at an advanced stage. Multiple multimodality treatments have gradually evolved into the main treatment for advanced EC, including surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. And the emergence of targeted therapy and immunotherapy has greatly improved the survival of EC patients. This review highlights the latest advances in targeted therapy and immunotherapy for EC, discusses the efficacy and safety of relevant drugs, summarizes related important clinical trials, and tries to provide references for therapeutic strategy of EC.

Abstract Background Given the serious consequences of depression and the lack of information about it during the crucially developmental period from the National College Entrance Exam (CEE, i.e., Chinese gaokao) to college, this study aimed to estimate the cumulative incidence, prevalence, age of onset, correlates, and service use of depressive disorders (DDs) among youth who passed the CEE and were enrolled at Hunan Normal University in China. Methods A two-stage cross-sectional epidemiological survey of DDs was conducted from October to December, 2017 among 6,922 incoming college students (98.5% effective response, N = 6,818, 71.4% female, age range: 16–25 years, mean age = 18.6). Using a stratified sampling method based on the risk of depression, 926 participants (mean age = 18.5, 75.2% female) were selected and subsequently interviewed with the Kiddie–Schedule for Affective Disorders and Schizophrenia–Present and lifetime version (K-SADS-PL). Results The sex-adjusted 9-month (i.e., 3 months pre-CEE, 3 months after CEE, and 3 months post-matriculation) incidence of new-onset DDs was 2.3% (standard error [S.E.] 0.3%), and the sex-adjusted 1-month, 6-month and lifetime prevalence were 0.7 (S.E. 0.3%), 1.7 (S.E. 0.2%) and 7.5% (S.E. 1.3%), respectively. The median age of onset was 17 (interquartile range: 16–18) years. Critically, over one-third (36.5%, S.E. 0.6) of depressed youth had their new onset during the 9-month period. The risk factors for depression included having mothers with higher education, experiencing major life events, being female, and experiencing parental divorce or death. The adjusted lifetime treatment rate was 8.7%. Conclusion The 9-month incidence of new-onset depression from gaokao to college among the youth sample in China is similar to the global annual incidence (3.0%), but the 1-month and lifetime prevalence are significantly lower than the global point (7.2%) and lifetime prevalence (19%). These findings suggest a high proportion of new-onset depression during the CEE to college among the sample youth in China. The risk of depression is associated with familial and stress correlates. Low treatment is a serious concern. Emphasis on early prevention and available treatment for adolescent and young adult depression is a critical need in China.

Protoplast has been widely used in biotechnologies to circumvent the breeding obstacles in citrus, including long juvenility, polyembryony, and male/female sterility. The protoplast-based transient gene expression system is a powerful tool for gene functional characterization and CRISPR/Cas9 genome editing in higher plants, but it has not been widely used in citrus. In this study, the polyethylene glycol (PEG)-mediated method was optimized for citrus callus protoplast transfection, with an improved transfection efficiency of 68.4%. Consequently, the efficiency of protein subcellular localization assay was increased to 65.8%, through transient expression of the target gene in protoplasts that stably express the fluorescent organelle marker protein. The gene editing frequencies in citrus callus protoplasts reached 14.2% after transient expression of CRISPR/Cas9 constructs. We demonstrated that the intronic polycistronic tRNA-gRNA (inPTG) genome editing construct was functional in both the protoplast transient expression system and epicotyl stable transformation system in citrus. With this optimized protoplast transient expression system, we improved the efficiency of protein subcellular localization assay and developed the genome editing system in callus protoplasts, which provides an approach for prompt test of CRISPR vectors.

Phloroglucinol is commonly used to alleviate dysmenorrhoea and stomach cramps. However, there is little evidence of phloroglucinol in the mechanism of primary dysmenorrhoea (PD) development. In this study, a PD rat model was established. The effects of phloroglucinol on the contraction of rat gastric circular muscle and uterine smooth muscle induced by oxytocin (OT) were investigated. The writhing response, and levels of oestradiol (E2), prostaglandin e2 (PGE2), and prostaglandin f2α (PGF2α) were determined. The protein and mRNA levels of OT receptor (OTR) were detected. OT showed a significant promoting effect on gastric circular muscle and uterine smooth muscle contraction. However, phloroglucinol strongly inhibited the contraction induced by 10−6 mol/L of OT. We also found that phloroglucinol reduced writhing response and attenuated uterine damage. Compared to the blank group, E2 and PGF2α were significantly increased, but PGE2 was significantly decreased in the PD model group. Phloroglucinol was found to reverse the changes of E2, PGF2α and PGE2. Moreover, phloroglucinol reduced the protein and mRNA levels of OTR. In conclusion, phloroglucinol could attenuate PD and inhibit the contraction of rat gastric circular muscle and uterine smooth muscle induced by OT. The mechanism might be related with the regulation of OTR expression.IMPACT STATEMENT What is already known on this subject? Phloroglucinol is commonly used to alleviate dysmenorrhoea and stomach cramps. However, there is little evidence of phloroglucinol in the mechanism of primary dysmenorrhoea (PD) development. What do the results of this study add? Phloroglucinol could attenuate PD and inhibit the contraction of rat gastric circular muscle and uterine smooth muscle induced by OT. The underlying mechanisms of phloroglucinol for PD treatment may be associated with OTR. What are the implications of these findings for clinical practice and/or further research? These findings provide novel ideas for the role of phloroglucinol in PD development.

Abstract Objective To compare the efficacy of dienogest and GnRH-a after endometriosis surgery. Methods Patients with endometriosis who were admitted to our hospital from December 2020 to March 2022 were randomly collected. A total of 81 patients were collected and divided into 40 cases in the control group and 41 cases in the observation group. Among them, the control group was treated with GnRH-a drug, and the observation group was treated with dienogest (DNG). Results The study found that the therapeutic effects of the two drugs were basically the same in patients with endometriosis. The VAS and Kupperman scores of the control group were 0.78 ± 0.8, 3.9 ± 1.84, P

This research aimed to provide an understanding of the selection and safe application of pipeline liner materials for hydrogen transport by examining the permeation properties and mechanisms of hydrogen within polymers commonly used for this purpose, such as high-density polyethylene (HDPE) and ethylene-vinyl alcohol copolymer (EVOH), through molecular simulation. The study was carried out within defined operational parameters of temperature (ranging from room temperature to 80 °C) and pressure (from 2.5 to 10 MPa) that are pertinent to hydrogen pipeline infrastructures. The results reveal that with an increase in temperature from 30 °C to 80 °C, the solubility, diffusion, and permeability coefficients of hydrogen in HDPE increase by 18.7%, 92.9%, and 129.0%, respectively. Similarly, in EVOH, these coefficients experience increments of 15.9%, 81.6%, and 112.7%. Conversely, pressure variations have a negligible effect on permeability in both polymers. HDPE exhibits significantly higher hydrogen permeability compared to EVOH. The unique chain segment configuration of EVOH leads to the formation of robust hydrogen bonds among the hydroxyl groups, thereby impeding the permeation of hydrogen. The process by which hydrogen is adsorbed in polymers involves aggregation at low potential energy levels. During diffusion, the hydrogen molecule primarily vibrates within a limited range, with intermittent occurrences of significant hole-to-hole transitions over larger distances. Hydrogen exhibits a stronger interaction with HDPE compared to EVOH, leading to a higher number of adsorption sites and increased hydrogen adsorption capacity in HDPE. Hydrogen molecules move more actively in HDPE than in EVOH, exhibiting greater hole amplitude and more holes in transition during the diffusion process.

BackgroundDomestic waste classification is one of the major livelihood projects in China. With the introduction of the Shanghai Household Waste Management Regulation in 2019, the work of domestic waste classification has been carried out nationwide, yet its potential risks especially those derived from microorganisms are not clear. ObjectiveTo investigate the microbial characteristics of the domestic waste in typical residential areas in Shanghai, and provide a theoretical basis for health protection during the domestic waste classification process in Shanghai and throughout China. MethodsDry and wet waste from a typical residential community in Shanghai were collected during 2019–2020. Microbial colonies were counted in domestic waste and analyzed for growth patterns. Then through 16S rRNA sequencing using lllumina PE250, hierarchical clustering analysis was conducted to reveal the similarity and dissimilarity of community compositions in different domestic waste groups, alpha diversity was estimated to reflect the richness and diversity of bacterial communities, principal co-ordinates analysis of unweighted UniFrac distance was performed to estimate the beta diversity, and linear discriminant analysis effect size (LEfSe) was used to find features differentially represented among domestic waste groups. ResultsIn the chosen typical residential community of this study, the numbers of microorganisms in waste were quite different, with lower numbers of microorganisms in dry waste than the numbers in wet waste. In addition, different growth curves of microorganisms were shown for different seasons, and the peak baterial colony numbers were 200 CFU·cm−2, 6×105 CFU·mL−1, 10 CFU·cm−2, and 2×106 CFU·mL−1 for summer dry waste, summer wet waste, winter dry waste, and winter wet waste, respectively. The results of 16S RNA demonstrated significant differences in α and β diversity indicators among different waste groups, and the difference in waste classifications was larger than the difference of the same classification of waste in different seasons. The main compositions of bacterial colonies in domestic waste was Proteobacteria, followed by Firmicute and Bacteroidota. The clustering analysis showed that the microbial composition in summer dry waste was close to that in winter dry waste, while other groups were quite different. In total 48 differential bacterial taxa were found at the level of genus including Pseudomonas and Pantoea. ConclusionDifferent seasons and different classifications of domestic waste present varied microbial characteristics, with different potential pathogenic microorganisms. Together with other related studies, we suggest that different measures should be taken for different domestic wastes to prevent and control the health hazards associated with waste classification.

This study presents the construction of a river channel and a bridge adjacent to existing metro tunnels in Changzhou. The influence of simultaneous construction on these existing tunnels was investigated via 3D numerical modelling to predict tunnel deformation before construction. Then, a targeted protection scheme was developed according to the obtained numerical results. The full construction period field monitoring scheme can monitor tunnel responses during construction. Subsequently, the safety of the tunnel structures was evaluated according to the monitoring results, and the evolution of tunnel deformations was analysed. The analytical results can help to clarify the influence characteristics of different construction stages, verify the effect of the proposed protection scheme, and determine the disturbance mechanism of short-distance pile construction. According to the results, the tunnel deformation mainly occurred during pile construction and river channel excavation, and the tunnel vertical displacement and convergence were mainly affected by the construction. The anti-floating scheme of the partition excavation and casting effectively controlled the tunnel heave with an alarm value of approximately 6 mm. The penetration of the short-distance casing resulted in a tunnel deformation. The main construction influence area of the casing pile was within 6D (D is the pile diameter).

Abstract Background Precision medicine highlights the importance of incorporating molecular genetic testing into standard clinical care. Next-generation sequencing can detect cancer-specific gene mutations, and molecular-targeted drugs can be designed to be effective for one or more specific gene mutations. For patients with special site metastases, it is particularly important to use appropriate samples for genetic profiling. This study aimed to determine whether genomic profiling using ASC and PE is effective in detecting genetic mutations. Methods Tissues, plasma, ascites (ASC) supernatants, and pleural effusion (PE) samples from gastrointestinal cancer patients with peritoneal metastasis and lung cancer patients with pleural metastasis were collected for comprehensive genomic profiling. The samples were subjected to next-generation sequencing using a panel of 59 or 1021 cancer-relevant genes panel. Results A total of 156 tissues, 188 plasma samples, 45 ASC supernatants, and 1 PE samples from 304 gastrointestinal cancer patients and 446 PE supernatants, 122 tissues, 389 plasma samples, and 45 PE sediments from 407 lung cancer patients were analyzed. The MSAF was significantly higher in ASC and PE supernatant than that in plasma ctDNA (50.00% vs. 3.00%, p

Recently, the adverse health effects of air pollution on human have attracted more and more attentions. Particulate matters (such as PM2.5 and PM10, with aerodynamic diameters ≤2.5 and ≤10 µm, respectively) and ozone are the major ambient pollutants in China. A large number of studies have shown that exposure to particulate matters or ozone induces metabolic abnormalities, such as type 2 diabetes. However, the underlying biological mechanisms are not clear. In this review, we introduced the epidemiological and toxicological research progress of the effects of air pollutants on hypothalamus-pituitary-adrenal (HPA) axis. Considering the critical role of HPA axis in stress response, the molecular mechanisms of HPA axis-mediated glucose metabolism in fat, liver, muscle, and other tissues were also summarized. By integrating relevant literature and references, we proposed that HPA axis may play an important role in the abnormal glucose metabolism caused by air pollution, providing a scientific basis for future studies on the intervention methods of adverse health effects induced by air pollution.

Multiple genetic changes in the enteric pathogen Yersinia pseudotuberculosis have driven the emergence of Yesinia pestis, the arthropod-borne, etiological agent of plague. These include developing the capacity for biofilm-dependent blockage of the flea foregut to enable transmission by flea bite. Previously, we showed that pseudogenization of rcsA, encoding a component of the Rcs signalling pathway, is an important evolutionary step facilitating Y. pestis flea-borne transmission. Additionally, rcsD, another important gene in the Rcs system, harbours a frameshift mutation. Here, we demonstrated that this rcsD mutation resulted in production of a small protein composing the C-terminal RcsD histidine-phosphotransferase domain (designated RcsD-Hpt) and full-length RcsD. Genetic analysis revealed that the rcsD frameshift mutation followed the emergence of rcsA pseudogenization. It further altered the canonical Rcs phosphorylation signal cascade, fine-tuning biofilm production to be conducive with retention of the pgm locus in modern lineages of Y. pestis. Taken together, our findings suggest that a frameshift mutation in rcsD is an important evolutionary step that fine-tuned biofilm production to ensure perpetuation of flea-mammal plague transmission cycles.

Oxidoreductases are a wide class of enzymes that can catalyze biological oxidation and reduction reactions. Nowadays, oxidoreductases play a vital part in most bioenergetic metabolic pathways, which have important applications in biodegradation, bioremediation, environmental applications, as well as biosensors. However, free oxidoreductases are not stable and hard to be recycled. In addition, cofactors are needed in most oxidoreductases catalyze reactions, which are so expensive and unstable that it hinders their industrial applications. Enzyme immobilization is a feasible strategy that can overcome these problems. Recently, metal–organic frameworks (MOFs) have shown great potential as support materials for immobilizing enzymes due to their unique properties, such as high surface-area-to-volume ratio, chemical stability, functional designability, and tunable pore size. This review discussed the application of MOFs and their composites as immobilized carriers of oxidoreductase, as well as the application of MOFs as catalysts and immobilized carriers in redox reactions in the perspective of the function of MOFs materials. The paper also focuses on the potential of MOF carrier-based oxidoreductase immobilization for designing an enzyme cascade reaction system.

Candida auris is a multidrug-resistant human fungal pathogen responsible for nosocomial outbreaks worldwide. Here, the authors identify differential innate immune responses induced by C. auris and Candida albicans in vitro and in vivo, which correlate with structural features of the cell wall.

Abstract. Gastric cancer (GC) is one of the most common malignant tumors worldwide. Its incidence ranks the 5th among all malignant tumors globally, and it is the 3rd leading cause of death among patients with cancer. Surgical treatment is the first choice in clinical practice. However, targeted therapy, immunotherapy, and other treatment methods have also become research hotspots at home and abroad with the development of individualized precision therapy in recent years, besides traditional radiotherapy and chemotherapy. At present, targeted therapy and immunotherapy are methods used for treating GC, and they have important clinical application value and prospects. This study aimed to review the research progress of targeted therapy and immunotherapy for GC, focusing on its mechanism of action and related important clinical trials, hoping to provide references for the clinical treatment of GC.

Due to the lack of timely and accurate screening modalities and treatments, most pancreatic cancer (PCa) patients undergo fatal PCa progression within a short period since diagnosis. The claudin(CLDN) family is expressed specifically as tight junction structure in a variety of tumors, including PCa, and affects tumor progression by changing the cell junctions. Thus far, many of the 27 members of the claudin family, including claudin-18.2 and claudin-4, have significantly aberrantly expression in pancreatic tumors. In addition, some studies have confirmed the role of some claudin proteins in the diagnosis and treatment of pancreatic tumors. By targeting different targets of claudin protein and combining chemotherapy, further enhance tumor cell necrosis and inhibit tumor invasion and metastasis. Claudins can either promote or inhibit the development of pancreatic cancer, which indicates that the diagnosis and treatment of different kinds of claudins require to consider different biological characteristics. This literature summarizes the functional characteristics and clinical applications of various claudin proteins in Pca cells, with a focus on claudin-18.2 and claudin-4.

Mature biofilm formation by Vibrio parahaemolyticus requires exopolysaccharide (EPS), type IV pili, and capsular polysaccharide (CPS). Production of each is strictly regulated by various control pathways including quorum sensing (QS) and bis-(3′–5′)-cyclic di-GMP (c-di-GMP). QsvR, an AraC-type regulator, integrates into the QS regulatory cascade via direct control of the transcription of the master QS regulators, AphA and OpaR. Deletion of qsvR in wild-type or opaR mutant backgrounds altered the biofilm formation by V. parahaemolyticus, suggesting that QsvR may coordinate with OpaR to control biofilm formation. Herein, we demonstrated both QsvR and OpaR repressed biofilm-associated phenotypes, c-di-GMP metabolism, and the formation of V. parahaemolyticus translucent (TR) colonies. QsvR restored the biofilm-associated phenotypic changes caused by opaR mutation, and vice versa. In addition, QsvR and OpaR worked coordinately to regulate the transcription of EPS-associated genes, type IV pili genes, CPS genes and c-di-GMP metabolism-related genes. These results demonstrated how QsvR works with the QS system to regulate biofilm formation by precisely controlling the transcription of multiple biofilm formation-associated genes in V. parahaemolyticus.

Objective To explore the epidemiological characteristics of patients with lymphoepithelial carcinoma (LEC) of the head and neck and the prognostic factors. Methods We conducted a retrospective cohort study of cases of head and neck LEC retrieved from the Surveillance, Epidemiology and End Results database. Kaplan–Meier survival analysis and the log-rank test were employed to assess overall survival (OS) and cancer-specific survival (CSS). Univariate and multivariate analyses were used to construct Cox regression models. We established nomograms to predict OS and CSS among patients with nasopharyngeal LEC, who were divided into high- and low-risk groups based on the OS nomograms to compare the effects of treatment using the restricted mean survival time (RMST). Results The 5-year OS and CSS rates of the cohort were 70.8% and 74.8%, respectively. Advanced age, unmarried status, black race, distant metastasis, and the absence of surgical treatment were significantly associated with decreased survival rates. RMST did not differ between the combined treatment (radiotherapy and chemotherapy) and radiotherapy monotherapy groups, but chemotherapy alone displayed poor efficacy. Conclusions Head and neck LEC is associated with a favorable prognosis. Radiotherapy plays a significant role in managing patients with nasopharyngeal LEC, which is influenced by multiple prognostic factors.

The undrained shear strength of clay is an important parameter for the design of embankments, shallow foundations, and pile foundations. Among the various methods of testing undrained strength, the simple shear is essential when the shearing mode of the soil surrounding the pile is similar to that in a simple shear test. This study employs a series of undrained strength tests with a Berkeley simple shear apparatus. Three reconstituted natural clays and one artificial clay were tested with a range of coefficients of consolidation. The influence factors, including sample pre-consolidation pressure, saturation back pressure, shearing rate, height of specimen, consolidation stress, and lateral stress ratio, were investigated in undrained simple shear tests. The failure mode in simple shear and corresponding strength parameters are also examined. Based on the test data set, models for describing the undrained strength with simple shear for high plasticity clays are developed and compared to test data for normally consolidated reconstituted clay. Good agreement between models and intact Onsoy clay is also observed when allowance is made for the coefficient of consolidation and strength parameters of undisturbed clay and in situ stress state.

Abstract Aerosol samplers are critical tools for studying indoor and outdoor aerosols. Development and evaluation of samplers is often labor-intensive and time-consuming due to the need to use monodisperse aerosols spanning a range of sizes. This study develops a rapid experimental methodology using polydisperse solid aerosols to evaluate size-resolved aerosol-to-aerosol (AtoA) and aerosol-to-hydrosol (AtoH) sampling efficiencies. Arizona Test Dust (diameter 0.5–20 µm) was generated and dispersed into an aerosol test chamber and two candidate samplers were tested. For the AtoA test, aerosols upstream and downstream of a sampler were measured using an online aerodynamic particle sizer. For the AtoH test, aerosols collected in sampling medium were mixed with a reference sample and then measured by the laser diffraction method. The experimental methodology were validated as an impressive time-saving procedure, with reasonable spatial uniformity and time stability of aerosols in the test chamber and an acceptable accuracy of absolute mass quantification of collected particles. Evaluation results showed that the AGI-30 and the BioSampler sampler had similar size-resolved sampling efficiencies and that efficiencies decreased with decreasing sampling flow rate. The combined evaluation of AtoA and AtoH efficiency provided more comprehensive performance indicators than either test alone. The experimental methodology presented here can facilitate the design and choice of aerosol sampler.

Siamese network based trackers regard visual tracking as a similarity matching task between the target template and search region patches, and achieve a good balance between accuracy and speed in recent years. However, existing trackers do not effectively exploit the spatial and inter-channel cues, which lead to the redundancy of pre-trained model parameters. In this paper, we design a novel visual tracker based on a Learnable Spatial and Channel-wise Transform in Siamese network (SiamLST). The SiamLST tracker includes a powerful feature extraction backbone and an efficient cross-correlation method. The proposed algorithm takes full advantages of CNN and the learnable sparse transform module to represent the template and search patches, which effectively exploit the spatial and channel-wise correlations to deal with complicated scenarios, such as motion blur, in-plane rotation and partial occlusion. Experimental results conducted on multiple tracking benchmarks including OTB2015, VOT2016, GOT-10k and VOT2018 demonstrate that the proposed SiamLST has excellent tracking performances.

In this study, 27SiMn was selected as a substrate, and the powder was a self-made iron-based alloy. Further, the thermophysical properties of the material were predicted by the CALPHAD phase diagram algorithm. In order to verify the accuracy of the numerical model, 10 sets of experiments were set up. The agreement between the results from the model calculations and the experimental results was 92%. Through the study of energy distribution in the laser cladding process, it was found that about 10% of the laser energy was used to heat the substrate to form a melt pool, and at least 53% of the energy was radiated into the environment. Finally, the effects of the temperature gradient and solidification rate on the microstructure of the cladding layer were explored. The numerical simulation results are helpful in predicting the solidification rate, temperature distribution and microstructure of the melt pool, thereby reducing the cost of testing as well as the time for the experimental method of trial–error.

Background: Ambient fine particulate matter (PM2.5) exposure increases local and systemic interleukin-6 (IL-6). However, the pathogenic role of IL-6 signalling following PM2.5 exposure, particularly in the development of pulmonary dysfunction and abnormal glucose homeostasis, has hardly been investigated. Results: In the study, IL-6 receptor (IL-6R)-deficient (IL-6R-/-) and wildtype littermate (IL-6R+/+) mice were exposed to concentrated ambient PM2.5 (CAP) or filtered air (FA), and their pulmonary and metabolic responses to these exposures were analyzed. Our results demonstrated that IL-6R deficiency markedly alleviated PM2.5 exposure-induced increases in lung inflammatory markers including the inflammation score of histological analysis, the number of macrophages in bronchoalveolar lavage fluid (BALF), and mRNA expressions of TNFα, IL-1β and IL-6 and abnormalities in lung function test. However, IL-6R deficiency did not reduce the hepatic insulin resistance nor systemic glucose intolerance and insulin resistance induced by PM2.5 exposure. Conclusion: Our findings support the crucial role of IL-6 signalling in the development of pulmonary inflammation and dysfunction due to PM2.5 exposure but question the putative central role of pulmonary inflammation for the extra-pulmonary dysfunctions following PM2.5 exposure, providing a deep mechanistic insight into the pathogenesis caused by PM2.5 exposure.

ABSTRACT Vibrio parahaemolyticus, a causative agent of seafood-associated gastroenteritis, undergoes opaque-translucent (OP-TR) colony switching associated with capsular polysaccharide (CPS) production. Here, we showed that V. parahaemolyticus was also able to naturally and reversibly switch between wrinkly and smooth phenotypes. More than 1,000 genes were significantly differentially expressed during colony morphology switching, including the major virulence gene loci and key biofilm-related genes. The genes responsible for type III secretion system 1 (T3SS1), type VI secretion systems (T6SS1 and T6SS2), and flagellar synthesis were downregulated in the wrinkly spreader phenotype, whereas genes located on the pathogenicity island Vp-PAI and those responsible for chitin-regulated pili (ChiRP) and Syp exopolysaccharide synthesis were upregulated. In addition, we showed that the wrinkly spreader grew faster, had greater motility and biofilm capacities, and produced more c-di-GMP than the smooth type. A dozen genes potentially associated with c-di-GMP metabolism were shown to be significantly differentially expressed, which may account for the differences in c-di-GMP levels between the two phenotypes. Most importantly, dozens of putative regulators were significantly differentially expressed, and hundreds of noncoding RNAs were detected during colony morphology switching, indicating that phenotype switching is strictly regulated by a complex molecular regulatory network in V. parahaemolyticus. Taken together, the presented work highlighted the gene expression profiles related to wrinkly-smooth switching, showing that the significantly differentially expressed genes were involved in various biological behaviors, including virulence factor production, biofilm formation, metabolism, adaptation, and colonization. IMPORTANCE We showed that Vibrio parahaemolyticus was able to naturally and reversibly switch between wrinkly and smooth phenotypes and disclosed the gene expression profiles related to wrinkly-smooth switching, showing that the significantly differentially expressed genes between the two colony morphology phenotypes were involved in various biological behaviors, including virulence factor production, biofilm formation, metabolism, adaptation, and colonization.

Background: There is growing evidence that allergic rhinitis (AR) is associated with indoor environmental factors, but their role in childhood AR during early life remains unclear. Objective: To investigate the association of preconceptional, prenatal, early postnatal, and current exposure to home environmental factors with childhood AR, and to further explore whether this association can be interacted by outdoor air pollution and temperature. Methods: A retrospective cohort study of 8689 preschool children was conducted during 2019–2020 in Changsha, China. A standard questionnaire was used to collect data on each family’s health outcomes and home environments. We considered home environmental exposures during one year before conception, pregnancy, first year of life, and past year. Associations of indoor air pollution and allergens with AR were assessed by multiple logistic regression models. Results: Pre-birth exposure to indoor air pollution emitted by new furniture or redecoration and dampness related allergen derived from mold/damp stains and mold/damp clothes or bedding during 1 year before conception and pregnancy was significantly associated with increased AR, with adjusted ORs (95% CI) ranging from 1.35 (1.05–1.75) to 1.87 (1.55–2.27). Childhood AR was also significantly related with post-birth exposure to dampness related indoor allergen including mold/damp stains and mold/damp clothes or bedding in first year and past year and pollen allergen including total and nonflowing plants in past year, with a range of ORs (95% CI) from 1.20 (1.01–1.42) to 1.79 (1.42–2.27). We identified that pre-birth, particularly in utero exposure to both indoor air pollution from renovation and dampness related allergens, played a key role in AR development compared to post-birth exposures, and accumulative effect was observed with the highest risk of AR. High exposure to traffic-related air pollution (TRAP) including outdoor PM2.5, NO2, CO, and O3, as well as living near traffic road not only significantly increased adverse effect of home environmental factors but also decreased protective effect of household dogs on childhood AR. Early life exposure to low temperature in pregnancy and high temperature in first year significantly increased AR risk of home environmental exposure. Sensitivity analysis indicated that some sub-groups were more susceptible to AR risk of home environmental exposure. Conclusion: Our study suggests that pre-birth exposure to home environmental factors played an important role in AR development and this effect can be interacted by TRAP and temperature, which supports a hypothesis of “(pre)fetal origin of childhood AR”.

The use of immune checkpoint inhibitors (ICIs) can improve survival of patients with malignant tumors, however, the ICI treatment is associated with unpredictable toxicity as immune-related adverse effects (irAEs). Here we report two cases of metastatic malignant gastrointestinal tumors where severe immune-mediated hepatotoxicity (IMH) developed, characterized by liver failure, after the ICI therapy. Through a strong immunosuppressive treatment and a non-biological artificial liver and supportive treatment, the liver function was restored in both cases, and the anti-tumor treatment effect was guaranteed. These results showed that the non-biological artificial liver could be capable of improve prognosis during the ICI therapy.

Cancer is a major public health problem that threatens human life worldwide. In recent years, immunotherapy has made great progress in both clinical and laboratory research. But the high heterogeneity and dynamics of tumors makes immunotherapy not suitable for all cancers. Dietary polyphenols have attracted researchers' attention due to their ability to induce cancer cell pyroptosis and to regulate the tumor immune microenvironment (TIME). This review expounds the regulation of dietary polyphenols and their new forms on cancer cell pyroptosis and the TIME. These dietary polyphenols include curcumin (CUR), resveratrol (RES), epigallocatechin gallate (EGCG), apigenin, triptolide (TPL), kaempferol, genistein and moscatilin. New forms of dietary polyphenols refer to their synthetic analogs and nano-delivery, liposomes. Studies in the past decade are included. The result shows that dietary polyphenols induce pyroptosis in breast cancer cells, liver cancer cells, oral squamous cells, carcinoma cells, and other cancer cells through different pathways. Moreover, dietary polyphenols exhibit great potential in the TIME regulation by modulating the programmed cell death protein 1(PD-1)/programmed death-ligand 1 (PD-L1) axis, enhancing antitumor immune cells, weakening the function and activity of immunosuppressive cells, and targeting tumor-associated macrophages (TAMs) to reduce their tumor infiltration and promote their polarization toward the M1 type. Dietary polyphenols are also used with radiotherapy and chemotherapy to improve antitumor immunity and shape a beneficial TIME. In conclusion, dietary polyphenols induce cancer cell pyroptosis and regulate the TIME, providing new ideas for safer cancer cures.

Polychlorinated diphenyl ethers (PCDEs) have been detected in various aquatic matrices, which pose potential threats to aquatic ecosystem security. In this work, both micro and macro analysis methods were used to assess the toxicity of PCDEs to zebrafish. Results indicated that after in vivo PCDE exposure, the oxidative stress and related gene of Danio rerio were significantly changed. The higher concentration or longer exposure time could cause more severe oxidative stress in zebrafish tissues. Compared with among the five tested compounds, more obvious changes in the level of oxidative biomarkers of lower chlorinated PCDEs’ (4-mono-CDE and 4,4′-di-CDE) exposure groups were observed. The integrated biomarker response analysis and gene expression results also indicate a similar trend. Histopathological observation suggested that 4,4′-di-CDE could render liver nuclei enlargement and necrosis, hepatocyte vacuolation, and the development inhibition of ovarian cells. Transmission electron microscope photos showed that 4,4′-di-CDE caused organelle damage in the liver and ovary, including the rupture of the endoplasmic reticulum, swelling of mitochondria, and condensation of chromatin in the liver and mitochondria disappeared significantly in the ovary. The degree of damage is enhanced with the increasing exposure doses. In addition, PCDEs also significantly altered vitellogenin content and related gene (vtg1) expression, suggesting that PCDEs may be estrogen endocrine disruptors. Overall, these results provided some valuable toxicological data of PCDEs on aquatic species.

Hypervirulent Klebsiella pneumoniae (hvKp) can cause life-threatening community-acquired infections among healthy young individuals and is thus of concern for global dissemination. In this study, a mouse model of acute primary hvKp pneumonia was established via aerosolized intratracheal (i.t.) inoculation, laying the foundation for conducting extensive studies related to hvKp. Subsequently, a time-course transcriptional profile was created of the lungs from the mouse model at 0, 12, 24, 48 and 60 hours post-infection (hpi) using RNA Sequencing (RNA-Seq). RNA-Seq data were analyzed with the use of Mfuzz time clustering, weighted gene co-expression network analysis (WGCNA) and Immune Cell Abundance Identifier for mouse (ImmuCellAI-mouse). A gradual change in the transcriptional profile of the lungs was observed that reflected expected disease progression. At 12 hpi, genes related to acute phase inflammatory response increased in expression and lipid metabolism appeared to have a pro-inflammatory effect. At 24 hpi, exacerbation of inflammation was observed and active IFN-γ suggested that signaling promoted activation and recruitment of macrophages occurred. Genes related to maintaining the structural integrity of lung tissues showed a sustained decrease in expression after infection and the decrease was especially marked at 48 hpi. TNF, IL-17, MAPK and NF-kB signaling pathways may play key roles in the immunopathogenesis mechanism at all stages of infection. Natural killer (NK) cells consistently decreased in abundance after infection, which has rarely been reported in hvKp infection and could provide a new target for treatment. Genes Saa1 and Slpi were significantly upregulated during infection. Both Saa1, which is associated with lipopolysaccharide (LPS) that elicits host inflammatory response, and Slpi, which encodes an antimicrobial protein, have not previously been reported in hvKp infections and could be important targets for subsequent studies. To t our knowledge, this paper represents the first study to investigate the pulmonary transcriptional response to hvKp infection. The results provide new insights into the molecular mechanisms underlying the pathogenesis of hvKp pulmonary infection that can contribute to the development of therapies to reduce hvKp pneumonia.

Abstract Background The membrane fusion protein (mfp) gene locus of Vibrio parahaemolyticus consists of two operons, cpsQ-mfpABC and mfpABC, which are both required for biofilm formation. ToxR and CalR are required for the full virulence of V. parahaemolyticus, and their mutual regulation has been demonstrated. Moreover, cell density-dependent expression of toxR was previously observed in V. parahaemolyticus, but details about the related mechanisms remained unclear. QsvR can work with the master quorum sensing (QS) regulators AphA and OpaR to regulate virulence expression and biofilm formation. Results In the present work, we showed that QsvR bound to the promoter-proximal DNA regions of toxR and calR to repress their transcription as well as occupying the regulatory regions of cpsQ-mfpABC and mfpABC to activate their transcription. Thus, we reconstructed the QsvR-dependent promoter organization of toxR, calR, cpsQ-mfpABC, and mfpABC. Conclusion QsvR directly repressed toxR and calR transcription as well as directly activated cpsQ-mfpABC and mfpABC transcription. The data presented here promotes us to gain deeper knowledge of the regulatory network of the mfp locus in V. parahaemolyticus.

Niobium-tungsten complex oxides have recently received interest for their use as energy storage materials in lithium-ion batteries. Here, atomic-resolution electron microcopy reveals their structure, including cation ordering.

The cysteine-rich polycomb-like protein (CPP) gene family is a class of transcription factors containing conserved cysteine-rich CRC structural domains that is involved in the regulation of plant growth and stress tolerance to adversity. Relative to other gene families, the CPP gene family has not received sufficient attention. In this study, six SlCPPs were identified for the first time using the most recent genome-wide identification data of tomato. Subsequently, a phylogenetic analysis classified SlCPPs into four subfamilies. The analysis of cis-acting elements in the promoter indicates that SlCPPs are involved in plant growth and development and also stress response. We present for the first time the prediction of the tertiary structure of these SlCPPs proteins using the AlphaFold2 artificial intelligence system developed by the DeepMind team. Transcriptome data analysis showed that SlCPPs were differentially expressed in different tissues. Gene expression profiling showed that all SlCPPs except SlCPP5 were up-regulated under drought stress; SlCPP2, SlCPP3 and SlCPP4 were up-regulated under cold stress; SlCPP2 and SlCPP5 were up-regulated under salt stress; all SlCPPs were up-regulated under inoculation with Cladosporium fulvum; and SlCPP1, SlCPP3, and SlCPP4 were up-regulated under inoculation with Stemphylium lycopersici. We performed a virus-induced gene silencing experiment on SlCPP3, and the results indicated that SlCPP3 was involved in the response to drought stress. Finally, we predicted the interaction network of the key gene SlCPP3, and there was an interaction relationship between SlCPP3 and 10 genes, such as RBR1 and MSI1. The positive outcome showed that SlCPPs responded to environmental stress. This study provides a theoretical and empirical basis for the response mechanisms of tomato in abiotic stresses.

USA300, a dominant clone of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), is circulating globally and can cause necrotizing pneumonia with high morbidity and mortality. To further reveal the host anti-MRSA infection immune response, we established a mouse model of acute primary MRSA pneumonia challenged with aerosols of the USA300 clone. A time-course transcriptome analysis of the lungs collected at 0, 12, 24, 48 and 96 h post-infection (hpi) was conducted using RNA sequencing (RNA-seq) and multiple bioinformatic analysis methods. The change trend of histopathology and five innate immune cell (neutrophils, mononuclear cells, eosinophils, macrophages, DC cells) proportions in the lungs after infection was also examined. We observed a distinct acute pulmonary recovery process. A rapid initiation period of inflammation was present at 12 hpi, during which the IL-17 pathway dominantly mediated inflammation and immune defense. The main stages of host inflammatory response occurred at 24 and 48 hpi, and the regulation of interferon activation and macrophage polarization played an important role in the control of inflammatory balance at this stage. At 96 hpi, cellular proliferation processes associated with host repair were observed, as well as adaptive immunity and complement system responses involving C1q molecules. More importantly, the data provide new insight into and identify potential functional genes involved in the checks and balances occurring between host anti-inflammatory and proinflammatory responses. To the best of our knowledge, this is the first study to investigate transcriptional responses throughout the inflammatory recovery process in the lungs after MRSA infection. Our study uncovers valuable research targets for key regulatory mechanisms underlying the pathogenesis of MRSA lung infections, which may help to develop novel treatment strategies for MRSA pneumonia.

Background: Lung cancer is the leading source of cancer-caused disability-adjusted life years. Medical cost burden impacts the well-being of patients through reducing income, cutting daily expenses, curtailing leisure activities, and depleting exhausting savings. The COmprehensive Score for Financial Toxicity (COST) was created and validated by De Souza and colleagues. Our study intends to measure the financial burdens of cancer therapy and investigate the link between financial toxicity and health-related quality of life (HRQoL) in an advanced lung cancer population.Methods: Patients aged ≥ 18 years with confirmed stage III to IV lung cancer were eligible. The COST questionnaire verified by de Souza et al. was used to identify financial toxicity. Multivariable linear regression analysis with log transformation univariate analysis and Pearson correlations were used to perform the analysis.Results: The majority of the patients (90.8%, n = 138/152) had an annual income of $50,000 ($7,775). The cohort's insurance situation was as follows: 64.5% of the cohort had social insurance, 20.4% had commercial insurance, and 22.0% had both. Patients who were younger age (50–59, P < 0.001), employed but on sick leave, and had lower income reported increased levels of financial toxicity (P < 0.05). The risk factors for high financial toxicity: (i) younger age (50–59), (ii)