Clinical characteristics and risk factors of Hepatitis E virus infection in Zhejiang Province: a multicenter case-control study.

Introduction: Hepatitis E (HE), caused by the Hepatitis E virus (HEV), is a significant cause of acute viral hepatitis globally and a major public health concern, particularly in specific high-prevalence areas in China, which have diverse transmission routes and regional differences. Identifying the primary risk factors for HE transmission is essential to develop targeted interventions for vulnerable populations. Methods: This study employed a 1:1 matched case-control methodology, using a standardized questionnaire complemented by medical records for data validation. Results: Among the 442 HE cases and 428 healthy controls, the case group had a higher prevalence of fatigue (46.21%) and loss of appetite (43.84%) compared to the control group. Furthermore, liver function indicators were significantly higher in the case group, with an average alanine aminotransferase (ALT) level of 621.94 U/L and aspartate aminotransferase (AST) level of 411.53 U/L. Severe HE patients were predominantly male, with significantly increased ALT and AST levels reaching 1443.81 U/L and 862.31 U/L respectively, along with a higher incidence of fatigue (90%) and loss of appetite (75%). Multifactorial analysis indicated that frequent dining out (OR = 2.553, 95%CI:1.686-3.868), poor hygiene conditions (OR = 3.889, 95%CI:1.399-10.807), and comorbid chronic illnesses (OR = 2.275, 95%CI:1.616-3.202) were risk factors for HE infection; conversely, good hygiene practices were protective factors against HE infection (OR = 0.698, 95%CI:0.521-0.934). Conclusion: In conclusion, HE infection in Zhejiang Province is closely associated with dietary habits and environmental hygiene, and individuals with chronic diseases or co-infections are at increased risk. This highlights the need for targeted health education to reduce the incidence of HE among these populations.

Two-Step Hydrothermal Synthesis of Submicrometric and Hierarchical Hollow SAPO-34 with Superior Catalytic Performance in Methanol to Olefin (MTO) Reaction.

A submicrometric and hierarchical hollow SAPO-34 molecular sieve was synthesized by an easy and low-cost two-step hydrothermal method. First, the crystallized mixture was obtained by direct drying after a first-step hydrothermal reaction. Then, the SAPO-34 product was obtained by adding the crystallized mixture to silicon-free gel and using cheap and common template agents. Compared to conventional SAPO-34, the submicrometric and hierarchical hollow SAPO-34 exhibits superior catalytic activity in the MTO reaction.

Efficient Self-Sorting Behaviours of Metallacages with Subtle Structural Differences.

Investigating the self-sorting behaviour of assemblies with subtle structural differences is a captivating yet challenging endeavour. Herein, we elucidate the unusual self-sorting behaviour of metallacages with subtle structural differences in batch reactors and microdroplets. Narcissistic self-sorting of metallacages has been observed for two ligands with identical sizes, shapes, and symmetries, with only minor differences in the substituted groups. In particular, the self-sorting process in microdroplets occurs within 1 min at room temperature, in stark contrast to batch reactors, which require equilibration for 30 min. To reveal the mechanism of self-sorting and the role of microdroplets, we conducted a series of experiments and theoretical calculations, including competitive self-assembly, cage-to-cage transformation, control experiments involving model metallacages with larger cavities, noncovalent interaction analysis, and root mean square deviation (RMSD) analysis. This research demonstrates an unusual case of self-sorting of very similar assemblies and provides a new strategy for facilitating the self-sorting efficiency of supramolecular systems.

Genetically evaluating the causal role of peripheral immune cells in colorectal cancer: a two-sample Mendelian randomization study.

BACKGROUND: Investigating novel therapeutic strategies for colorectal cancer (CRC) is imperative. However, there is limited research on the use of drugs to target peripheral blood immune cells in this context. To address this gap, we performed a two-sample Mendelian randomization (MR) analysis to identify potential therapeutic targets for CRC. METHODS: We applied two-sample MR to identify the causal relationship between peripheral blood immune cells and CRC. GWAS data were obtained from the IEU OPEN GWAS project. Based on the implications from the MR results, we conducted a comprehensive database search and genetic analysis to explore potential underlying mechanisms. We predicted miRNAs for each gene and employed extensive research for potential therapeutic applications. RESULTS: We have identified causal associations between two peripheral immune cells and colorectal cancer. Activated & resting Treg %CD4 + cell was positively associated with the risks of CRC, while DN (CD4-CD8-) %leukocyte cell exhibited a protective role in tumor progression. NEK7 (NIMA related kinase 7) and LHX9 (LIM homeobox 9) expressed in Treg cells were positively associated with CRC risks and may play a vital role in carcinogenesis. CONCLUSIONS: This study identified causal relationship between peripheral immune cell and CRC. Treg and DN T cells were implicated to own promoting and inhibiting effects on CRC progression respectively. NEK7 and LHX9 in Treg cells were identified as potential biotarget for antitumor therapies.

Microfluidic-Based dsRNA Delivery Nanoplatform for Efficient Spodoptera exigua Control.

Nanotechnology-based RNA interference (RNAi) offers a promising approach to pest control. However, current methods for producing RNAi nanopesticides are mainly implemented in a batch-to-batch manner, lacking consistent quality control. Herein, we present a microfluidic-based nanoplatform for RNA nanopesticide preparation using lipid nanoparticles (LNPs) as nanocarriers, taking advantage of the enhanced mass transfer and continuous processing capabilities of microfluidic technology. The dsRNA@LNPs were rapidly formed within seconds, which showed uniform size distribution, improved leaf wettability, and excellent dispersion properties. The delivery efficiency of dsRNA@LNPs was evaluated by targeting the chitin synthetase B (CHSB) gene ofSpodoptera exigua. The dsRNA@LNPs can effectively resist nuclease-rich midgut fluid degradation. Importantly, dsCHSB@LNPs exhibited increased mortality rates, significant reduction of larvae growth, and enhanced gene suppression efficiency. Therefore, a continuous nanoplatform for RNAi nanopesticide preparation is demonstrated by utilizing microfluidic technology, representing a new route to produce RNAi nanopesticides with enhanced quality control and might accelerate their practical applications.

Prevalence of Respiratory Viruses in Children With Acute Respiratory Infections in Shanghai, China, From 2013 to 2022.

BACKGROUND: A variety of viruses can cause acute respiratory infections (ARIs), resulting in a high disease burden worldwide. To explore the dominant viruses and their prevalence characteristics in children with ARIs, comprehensive surveillance was carried out in the Pudong New Area of Shanghai. METHODS: Between January 2013 and December 2022, the basic and clinical information, and respiratory tract specimens of 0-14 years old children with ARIs were collected in five sentinel hospitals in Shanghai Pudong. Each specimen was tested for eight respiratory viruses, and the positive rates of different age groups, case types (inpatient or outpatient) were analyzed. RESULTS: In our study, 30.67% (1294/4219) children with ARIs were positive for at least one virus. Influenza virus (IFV) was the most commonly detected respiratory virus (349/4219, 8.27%), followed by respiratory syncytial virus (RSV) (217/4219, 5.14%), para-influenza virus (PIV) (215/4219, 5.10%), and human coronavirus (HCoV, including 229E, OC43, NL63, and HKU1) (184/4219, 4.36%). IFV was the leading respiratory virus in outpatients aged 5-14 years (201/1673, 12.01%); RSV was the most prevalent respiratory virus in both inpatients (61/238, 25.63%) and outpatients (4/50, 8.00%) for ARI patients aged <6 months old. For PIV, HMPV, HCoV, and HRV, the risk of infection usually was higher among young children. Co-infection with more than two viruses was seen in 3.25% (137/4219). CONCLUSIONS: IFV and RSV played important roles in ARIs among children, but the risk populations were different. There are needs for targeted diagnosis and treatment and necessary immunization and non-pharmaceutical interventions.

Prioritization of therapeutic targets for cancers using integrative multi-omics analysis.

BACKGROUND: The integration of transcriptomic, proteomic, druggable genetic and metabolomic association studies facilitated a comprehensive investigation of molecular features and shared pathways for cancers' development and progression. METHODS: Comprehensive approaches consisting of transcriptome-wide association studies (TWAS), proteome-wide association studies (PWAS), summary-data-based Mendelian randomization (SMR) and MR were performed to identify genes significantly associated with cancers. The results identified in above analyzes were subsequently involved in phenotype scanning and enrichment analyzes to explore the possible health effects and shared pathways. Additionally, we also conducted MR analysis   to investigate metabolic pathways related to cancers. RESULTS: Totally 24 genes (18 transcriptomic, 1 proteomic and 5 druggable genetic) showed significant associations with cancers risk. All genes identified in multiple methods were mainly enriched in nuclear factor erythroid 2-related factor 2 (NRF2) pathway. Additionally, biosynthesis of ubiquinol and urate were found to play an important role in gastrointestinal tumors. CONCLUSIONS: A set of putatively causal genes and pathways relevant to cancers were identified in this study, shedding light on the shared biological processes for tumorigenesis and providing compelling genetic evidence to prioritize anti-cancer drugs development.

Clinical and molecular heterogeneity associated with tumor sidedness in colorectal liver metastasis: a multicenter propensity cohort study.

Background: Colorectal liver metastasis (CRLM) exhibits highly heterogeneity, with clinically and molecularly defined subgroups that differ in their prognosis. The aim of this study is to explore whether left-sided tumors is clinically and gnomically distinct from right-sided tumors in CRLM. Methods: This retrospective study included 1,307 patients who underwent primary tumor and metastases resection at three academic centers in China from January 1, 2012, to December 31, 2020. Propensity score matching with 1:1 ratio matching was performed. The prognostic impact of tumor sidedness was determined after stratifying by the KRAS mutational status. Moreover, whole-exome sequencing (WES) of 200 liver tumor tissues were performed to describe the heterogeneity across the analysis of somatic and germline profiles. Results: The median follow-up was 68 months. Matching yielded 481 pairs of patients. Compared to right-sided CRLM, left-sided patients experienced with better 5-year overall survival (OS) in surgery responsiveness, with a 14.6 lower risk of death [hazard ratio (HR), 1.36, 95% confidence interval (CI), 1.10-1.69, P=0.004]. Interaction between tumor sidedness and KRAS status was statistically significant: left-sidedness was associated with better prognosis among KRAS wild-type patients (HR 1.71; 95% CI: 1.20-2.45; P=0.003), but not among KRAS mutated-type patients. Integrated molecular analyses showed that right-sided tumors more frequently harbored TP53, APC, KRAS, and BRAF alterations, and identified a critical role of KRAS mutation in correlation with their survival differences. Higher pathogenic germline variants were identified in the right-sided tumors compared with left-sided tumors (29.3% vs. 15.5%, P=0.03). Conclusions: We demonstrated that the prognostic impacts of tumor sidedness in CRLM is restricted patients with KRAS wild-type tumors. Tumor sidedness displays considerable clinical and molecular heterogeneity that may associate with their therapy benefits and prognosis.

A novel feature-level fusion scheme with multimodal attention CNN for heart sound classification.

BACKGROUND AND OBJECTIVE: Most of the existing machine learning-based heart sound classification methods achieve limited accuracy. Since they primarily depend on single domain feature information and tend to focus equally on each part of the signal rather than employing a selective attention mechanism. In addition, they fail to exploit convolutional neural network (CNN) - based features with an effective fusion strategy. METHODS: In order to overcome these limitations, a novel multimodal attention convolutional neural network (MACNN) with a feature-level fusion strategy, in which Mel-cepstral domain as well as general frequency domain features are incorporated to increase the diversity of the features, is proposed in this paper. In the proposed method, DilationAttenNet is first utilized to construct attention-based CNN feature extractors and then these feature extractors are jointly optimized in MACNN at the feature-level. The attention mechanism aims to suppress irrelevant information and focus on crucial diverse features extracted from the CNN. RESULTS: Extensive experiments are carried out to study the efficacy of the feature level fusion in comparison to that with early fusion. The results show that the proposed MACNN method significantly outperforms the state-of-the-art approaches in terms of accuracy and score for the two publicly available Github and Physionet datasets. CONCLUSION: The findings of our experiments demonstrated the high performance for heart sound classification based on the proposed MACNN, and hence have potential clinical usefulness in the identification of heart diseases. This technique can assist cardiologists and researchers in the design and development of heart sound classification methods.

The Characteristics of the Influenza Virus Epidemic Around the SARS-CoV-2 Epidemic Period in the Pudong New Area of Shanghai.

OBJECTIVES: The concurrent impact of COVID-19 and influenza on disease burden is a topic of great concern. This discussion delves into the epidemiological characteristics of seasonal influenza activity in Shanghai within the context of the SARS-CoV-2 epidemic. METHODS: From 2017 to 2023, a total of 11,081 patients having influenza-like illness (ILI) were included in this study for influenza virus detection. Reverse transcription polymerase chain reaction (RT-PCR) assays were conducted according to standardised protocols to identify the types and subtypes of influenza viruses. The positivity rate of the influenza virus among the sampled ILI cases served as a surrogate measure for estimating various influenza seasonal characteristics, such as periodicity, duration, peak occurrences, and the prevalent subtypes or lineages. Epidemiological aspects across different years and age groups were subjected to comprehensive analysis. For categorical variables, the Chi-square test or Fisher's exact test was employed, as deemed appropriate. RESULTS: A total of 1553 (14.0%) tested positive for influenza virus pathogens. The highest positivity rate for influenza was observed in adults aged 25-59 years (18.8%), while the lowest rate was recorded in children under 5 years (3.8%). The influenza circulation patterns in Shanghai were characterised: (1) 2 years exhibited semiannual periodicity (2017-2018, 2022-2023); (2) 3 years displayed annual periodicity (2018-2019, 2019-2020, and 2021-2022); and (3) during 2020-2021, epidemic periodicities of seasonal influenza viruses disappeared. In terms of influenza subtypes, four subtypes were identified during 2017-2018. In 2018-2019 and 2019-2020, A/H3N2, A/H1N1, and B/Victoria were circulating. Notably, one case of B/Victoria was detected in 2020-2021. The epidemic period of 2021-2022 was attributed to B/Victoria, and during 2022-2023, the influenza A virus was the dominant circulating strain. CONCLUSIONS: The seasonal epidemic period and the predominant subtype/lineage of influenza viruses around the SARS-CoV-2 epidemic period in Shanghai city are complex. This underscores the necessity for vigilant influenza control strategies amidst the backdrop of other respiratory virus pandemics.

Changes of influenza vaccination rate and associated influencing factors after the COVID-19 pandemic in Shanghai, China.

The vaccination rate for seasonal influenza remains low in most regions of China. It is essential to understand the factors that associated with the low influenza vaccination rate in various populations after the COVID-19 pandemic. A cross-sectional survey was conducted with residents in Pudong New Area, Shanghai, China. Respondents' vaccination condition during the 2021-2022 flu season and the reasons for receiving or not receiving influenza vaccine were investigated. Binary logistic regression was conducted to explore potential factors influencing vaccination uptake. 2,476 of 14,001 respondents received an influenza vaccine, with a total coverage of 17.68% (95% CI: 17.05%, 18.32%). Children had the highest vaccination coverage (35.68%; 95% CI: 34.02, 37.33), followed by adults (12.75%; 95% CI: 11.91%, 13.58%) and elderly individuals (11.70%, 95% CI: 10.78%, 12.62%). For children, lower household income was an significant promoting factor. For adults, factors significantly associated with vaccination were household income, sex, and education level. For elderly, factors significantly associated with vaccination were household income, education level, living state, and having underlying diseases. (P < .05)The main reason for vaccine hesitancy among children was worried about side effects (21.49%), for adults and elderly was self-rated good health (adults: 37.14%, elderly people: 30.66%). The overall influenza vaccination coverage rate in Shanghai, especially among elderly individuals, is lower than many developed countries. Appropriate strategies and programs targeting different populations need to be implemented to enhance influenza vaccine coverage.

The vaccination rate for seasonal influenza remains low in most regions of China. However, the COVID-19 pandemic has resulted in an increase in public awareness regarding the prevention and control of infectious diseases and changes in people's health behaviors thus may leading to changes in influenza vaccination rates and vaccination willingness. We conducted a survey on the medical service utilization behavior of community residents in Shanghai, the biggest city in eastern China. The vaccination status of respondents during the 2021­2022 flu season and the reasons for receiving or not receiving the vaccine were investigated among 14,001 local residents. The influenza vaccination rate in 2021­2022 season (17.68%) was higher than that in 2018­2019 season (11.8%) in the same area. And this trend was found in population of different age groups. However, the overall influenza vaccination coverage rate in Shanghai is still low, especially among elderly, it remains inadequate to establish an immune barrier and lags behind other developed regions. For children, lower household income was an independent promoting factor. For adults, factors significantly associated with vaccination were  household income, sex, and education level. For elderly, factors significantly associated with vaccination were household income, education level, living state, and having underlying diseases. (P < .05) The main reason for vaccine hesitancy among children was worried about side effects (21.49%), for adults and elderly was self-rated good health (adults: 37.14%,elderly people: 30.66%).Efforts should be made to increase awareness of influenza vaccines according to the characteristics of different population.

Site 1 protease aggravates acute kidney injury by promoting tubular epithelial cell ferroptosis through SIRT3-SOD2-mtROS signaling.

Ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) is a common clinical syndrome with high morbidity and mortality. Ferroptosis, a newly discovered form of oxidative cell death, is involved in the pathogenesis of renal I/R injury; however, the underlying mechanism remains to be explored. Here, we reported that site 1 protease (S1P) promotes ischemic kidney injury by regulating ferroptotic cell death of tubular epithelial cells. S1P abundance was measured in hypoxia/reoxygenation (H/R)-treated Boston University mouse proximal tubular (BUMPT) cells and I/R-induced murine kidney tissue. S1P expression in BUMPT cells and kidneys was initially activated by hypoxic stimulation, accompanied by the ferroptotic response. Blocking S1P blunted H/R-induced ferroptotic cell death, which also restored sirtuin 3 (SIRT3) expression and superoxide dismutase 2 (SOD2) activity in BUMPT cells. Next, inhibition of S1P expression restored I/R-suppressed SIRT3 abundance, SOD2 activity and reduced the elevated level of mitochondria reactive oxygen species (mtROS), which attenuated tubular cell ferroptosis and renal I/R injury. In conclusion, S1P promoted renal tubular epithelial cell ferroptosis under I/R status by activating SIRT3-SOD2-mtROS signaling, thereby accelerating kidney injury. Thus, targeting S1P signaling may serve as a promising strategy for I/R kidney injury.