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Background Recently, attention has focused on the impact of global climate change on infectious diseases. Storm flooding is an extreme weather phenomenon that not only impacts the health of the environment but also worsens the spread of pathogens. This poses a significant challenge to public health security. However, there is still a lack of research on how different levels of storm flooding affect susceptible enteric infectious diseases over time. Methods Data on enteric infectious diseases, storm flooding events, and meteorology were collected for Changsha, Hunan Province, between 2016 and 2020. The Wilcoxon Rank Sum Test was used to identify the enteric infectious diseases that are susceptible to storm flooding. Then, the lagged effects of different levels of storm flooding on susceptible enteric infectious diseases were analyzed using a distributed lag nonlinear model. Results There were eleven storm flooding events in Changsha from 2016 to 2020, concentrated in June and July. 37,882 cases of enteric infectious diseases were reported. During non-flooding days, the daily incidence rates of typhoid/paratyphoid and bacillary dysentery were 0.3/100,000 and 0.1/100,000, respectively. During flooding days, the corresponding rates increased to 2.0/100,000 and 0.8/100,000, respectively. The incidence rates of both diseases showed statistically significant differences between non-flooding and flooding days. Correlation analysis shows that the best lags for typhoid/paratyphoid and bacillary dysentery relative to storm flooding events may be 1 and 3 days. The results of the distributed lag nonlinear model showed that typhoid/paratyphoid had the highest cumulative RR values of 2.86 (95% CI: 1.71–4.76) and 8.16 (95% CI: 2.93–22.67) after 4 days of general flooding and heavy flooding, respectively; and bacillary dysentery had the highest cumulative RR values of 1.82 (95% CI: 1.40–2.35) and 3.31 (95% CI: 1.97–5.55) after 5 days of general flooding and heavy flooding, respectively. Conclusions Typhoid/paratyphoid and bacillary dysentery are sensitive enteric infectious diseases related to storm flooding in Changsha. There is a lagging effect of storm flooding on the onset of typhoid/paratyphoid and bacillary dysentery, with the best lagging periods being days 1 and 3, respectively. The cumulative risk of typhoid/paratyphoid and bacillary dysentery was highest at 4/5 days lag, respectively. The higher of storm flooding, the higher the risk of disease, which suggests that the authorities should take appropriate preventive and control measures before and after storm flooding.

This study retrospectively analyzed the spatio-temporal distribution and spatial clustering of scarlet fever in mainland China from 2004 to 2017. In recent years, the incidence of scarlet fever is increasing. Previous studies on the spatial distribution of scarlet fever in China are mainly focused at the provincial and municipal levels, and there is few systematic report on the spatial and temporal distribution characteristics of scarlet fever on the national level. Based on the incidence information of scarlet fever in mainland China between 2004 and 2017 collected from the China Center for Disease Control, this paper systematically explored the Spatio-temporal distribution of scarlet fever by three methods, contains spatial autocorrelation analysis, Spatio-temporal scanning analysis, and trend surface analysis. The results demonstrate that the incidence of scarlet fever varies by seasons, which is in line with double-peak distribution.The first peak generally occurs from May to June and the second one from November to December, while February and August is the lowest period of incidence. Trend surface analysis indicates that the incidence of scarlet fever in northern China is higher than the south, slightly higher in western compared to the east, and lower in the central part. Additionally, the results show that the clustering regions of scarlet fever centrally distributed in the northeast, northwest, north china and some provinces in the east, such as Zhejiang, Shanghai, Shandong, and Jiangsu.       

BackgroundA large number of new causative and risk genes for amyotrophic lateral sclerosis (ALS) have been identified mostly in patients of European ancestry. In contrast, we know relatively little regarding the genetics of ALS in other ethnic populations. This study aims to provide a comprehensive analysis of the genetics of ALS in an unprecedented large cohort of Chinese mainland population and correlate with the clinical features of rare variants carriers.MethodsA total of 1587 patients, including 64 familial ALS (FALS) and 1523 sporadic ALS (SALS), and 1866 in-house controls were analysed by whole-exome sequencing and/or testing for G4C2 repeats in C9orf72. Forty-one ALS-associated genes were analysed.Findings155 patients, including 26 (40.6%) FALS and 129 (8.5%) SALS, carrying rare pathogenic/likely pathogenic (P/LP) variants of ALS causative genes were identified. SOD1 was the most common mutated gene, followed by C9orf72, FUS, NEK1, TARDBP and TBK1. By burden analysis, rare variants in SOD1, FUS and TARDBP contributed to the collective risk for ALS (p<2.5e-6) at the gene level, but at the allelic level TARDBP p.Gly294Val and FUS p.Arg521Cys and p.Arg521His were the most important single variants causing ALS. Clinically, P/LP variants in TARDBP and C9orf72 were associated with poor prognosis, in FUS linked with younger age of onset, and C9orf72 repeats tended to affect cognition.ConclusionsOur data provide essential information for understanding the genetic and clinical features of ALS in China and for optimal design of genetic testing and evaluation of disease prognosis.

Whole-exome sequencing has been successful in identifying genetic factors contributing to familial or sporadic Parkinson’s disease (PD). However, this approach has not been applied to explore the impact of de novo mutations on PD pathogenesis. Here, we sequenced the exomes of 39 early onset patients, their parents, and 20 unaffected siblings to investigate the effects of de novo mutations on PD. We identified 12 genes with de novo mutations (MAD1L1, NUP98, PPP2CB, PKMYT1, TRIM24, CEP131, CTTNBP2, NUS1, SMPD3, MGRN1, IFI35, and RUSC2), which could be functionally relevant to PD pathogenesis. Further analyses of two independent case-control cohorts (1,852 patients and 1,565 controls in one cohort and 3,237 patients and 2,858 controls in the other) revealed that NUS1 harbors significantly more rare nonsynonymous variants (P = 1.01E-5, odds ratio = 11.3) in PD patients than in controls. Functional studies in Drosophila demonstrated that the loss of NUS1 could reduce the climbing ability, dopamine level, and number of dopaminergic neurons in 30-day-old flies and could induce apoptosis in fly brain. Together, our data suggest that de novo mutations could contribute to early onset PD pathogenesis and identify NUS1 as a candidate gene for PD.

The formation of auxin glucose conjugate is proposed to be one of the molecular modifications controlling auxin homeostasis. However, the involved mechanisms and relevant physiological significances are largely unknown or poorly understood. In this study, Arabidopsis UGT75D1 was at the first time identified to be an indole-3-butyric acid (IBA) preferring glycosyltransferase. Assessment of enzyme activity and IBA conjugates in transgenic plants ectopically expressing UGT75D1 indicated that the UGT75D1 catalytic specificity was maintained in planta. It was found that the expression pattern of UGT75D1 was specific in germinating seeds. Consistently, we found that transgenic seedlings with over-produced UGT75D1 exhibited smaller cotyledons and cotyledon epidermal cells than the wild type. In addition, UGT75D1 was found to be up-regulated under mannitol, salt and ABA treatments and the over-expression lines were tolerant to osmotic and salt stresses during germination, resulting in an increased germination rate. Quantitative RT-PCR analysis revealed that the mRNA levels of ABA INSENSITIVE 3 (ABI3) and ABI5 gene in ABA signaling were substantially down-regulated in the transgenic lines under stress treatments. Interestingly, AUXIN RESPONSE FACTOR 16 (ARF16) gene of transgenic lines was also dramatically down-regulated under the same stress conditions. Since ARF16 functions as an activator of ABI3 transcription, we supposed that UGT75D1 might play a role in stress tolerance during germination through modulating ARF16–ABI3 signaling. Taken together, our work indicated that, serving as the IBA preferring glycosyltransferase but distinct from other auxin glycosyltransferases identified so far, UGT75D1 might be a very important player mediating a crosstalk between cotyledon development and stress tolerance of germination at the early stage of plant growth.

This study employed a multi-technique approach to investigate the structural and conformational changes in proteins in ( ) adductor, foot, and siphon tissues during boiling. Data-independent acquisition (DIA) quantitative proteomics was utilized to identify differentially expressed proteins (DEPs) in six temporal comparison groups (20-0 s, 40-20 s, 60-40 s, 80-60 s, 100-80 s, and 120-100 s). The results showed that key myofibrillar proteins, including myosin heavy chain, paramyosin, and actin, exhibited tissue-specific expression patterns, while low-molecular-weight degradation fragments (<17 kDa) appeared with prolonged heating. Turbidity measurements peaked in adductor and siphon tissues at 60 s and in foot tissue at 80 s. Heating resulted in a narrowed particle size distribution (100-1000 nm), and a decreased zeta potential, indicating a reduction in protein surface charge. Fourier transform infrared spectroscopy revealed hydrogen bond disruption and secondary structure transitions, marked by a reduction in α-helix content with a corresponding increase in β-sheet and random coil structures. In total, 6527 proteins were identified, and Gene Ontology (GO) enrichment analysis highlighted the DEPs' involvement in biological regulation and metabolic processes. Collectively, these results provide comprehensive characterization of protein denaturation, degradation, and structural reorganization in tissues during the boiling process.

Background Colon cancer remains one of the leading causes of cancer-related deaths worldwide and is associated with high rates of recurrence and metastasis despite advances in therapy. The tumor microenvironment (TME), characterized by complex immune and stromal interactions, plays a pivotal role in tumor progression and treatment resistance. Neutrophil extracellular traps (NETs), an emerging component of the TME, have been implicated in promoting tumor invasion, metastasis, and immune evasion. However, their specific role in colon cancer remains unclear. Methods Comprehensive transcriptomic analyses were conducted using datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to identify NETs-associated genes involved in colon cancer. Single-cell RNA sequencing (scRNA-seq) was utilized to assess cellular heterogeneity, and spatial transcriptomics mapped NETs activity and cell–cell interactions within the TME. A prognostic model was constructed using multivariate Cox and LASSO regression analyses based on key NETs-related genes. Model performance was validated using internal and external cohorts. Additionally, colocalization analysis between TUBB2A eQTL signals and colorectal cancer overall survival GWAS effects was performed to investigate potential genetic correlations. Results Two distinct NETs-related molecular subtypes of colon cancer were identified, differing in immune composition, metabolic activity, and gene expression profiles. NETs-high malignant cells demonstrated metabolic reprogramming involving oxidative phosphorylation and cellular respiration, contributing to immune escape and therapeutic resistance. A four-gene prognostic signature ( ARRDC1, TUBB2A, DUSP5 , and SLC2A3 ) was developed and showed moderate prognostic discrimination across internal and external cohorts, indicating potential value for risk stratification but limited predictive accuracy at the current stage. Colocalization analysis revealed a modest negative correlation between TUBB2A expression and overall survival and cancer-specific survival, suggesting that increased TUBB2A expression may be associated with adverse clinical outcomes. Conclusions This study reveals that NETs-associated genes play crucial roles in colon cancer progression, immune modulation, and metabolic reprogramming. The identified four-gene signature may serve as a candidate biomarker for risk stratification in colon cancer, although further validation is needed.

Background and aimHuntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder caused by CAG repeats expansion. Cognitive decline contributes to the loss of daily activity in manifest HD. We aimed to examine the cognition status in a Chinese HD cohort and explore factors influencing the diverse cognitive domains.MethodsA total of 205 participants were recruited in the study with the assessment by neuropsychological batteries, including the mini–mental state examination (MMSE), Stroop test, symbol digit modalities test (SDMT), trail making test (TMT), verbal fluency test (VFT), and Hopkins verbal learning test–revised, as well as motor and psychiatric assessment. Pearson correlation and multiple linear regression models were applied to investigate the correlation.ResultsOnly 41.46% of patients had normal global function first come to our center. There was a significantly difference in MMSE, Stroop test, SDMT, TMT, and VFT across each stage of HD patients (p < .05). Apathy of PBA-s was correlated to MMSE, animal VFT and Stroop-interference tests performance. Severity of motor symptoms, functional capacity, age, and age of motor symptom onset were correlated to all neuropsychological scores, whereas education attainment and diagnostic delay were correlated to most neuropsychological scores except TMT. Severity of motor symptoms, functional capacity, and education attainment showed independent predicting effect (p < .05) in diverse cognitive domains.ConclusionCognitive impairment was very common in Chinese HD patients at the first visit and worse in the patients in advanced phase. The severity of motor symptoms and functional capacity were correlated to the diverse cognitive domains.

Natural polymeric proteins, isolated from scallop gonad, had already shown promise as a potent nutraceutical. The purpose of this study was to fabricate scallop gonad protein isolates (SGPIs) as a natural alternative emulsifier designed for improving the physicochemical stability of β-carotene (BC). The influence of carrier oil, including long- and medium-chain triglycerides (LCT/MCT), on the physicochemical stability of BC emulsions was investigated. The SGPI-stabilized BC emulsions were characterized in terms of viscosity, particle diameter, zeta-potential, atomic force microscopy (AFM), cryogenic scanning electron microscopy (cryo-SEM), and confocal laser scanning microscopy (CLSM). Compared to SGPI-MCT emulsions, SGPI-LCT emulsions had better resistance to high ionic strengths and thermal treatment. During the 30-day storage period, the particle diameter, zeta-potential, and BC degradation of both emulsions had a great change at 37 °C than at 25 or 4 °C, and the variation of SGPI-MCT emulsions was more obvious than that of SGPI-LCT, which could be attributed to the high viscosity of SGPI-LCT emulsions. These results indicate that SGPIs can be applied in protecting lipophilic bioactives by using emulsion-based systems, in which LCT oil was more effective for encapsulating and protecting BC than MCT oil. Graphical abstract

Background Polypodiales suborder Dennstaedtiineae contain a single family Dennstaedtiaceae, eleven genera, and about 270 species, and include some groups that were previously placed in Dennstaedtiaceae, Hypolepidaceae, Monachosoraceae, and Pteridaceae. The classification and phylogenetic relationships among these eleven genera have been poorly understood. To explore the deep relationships within suborder Dennstaedtiineae and estimate the early diversification of this morphologically heterogeneous group, we analyzed complete plastomes of 57 samples representing all eleven genera of suborder Dennstaedtiineae using maximum likelihood and Bayesian inference. Results The phylogenetic relationships of all the lineages in the bracken fern family Dennstaedtiaceae were well resolved with strong support values. All six genera of Hypolepidoideae were recovered as forming a monophyletic group with full support, and Pteridium was fully supported as sister to all the other genera in Hypolepidoideae. Dennstaedtioideae ( Dennstaedtia s.l. ) fell into four clades with full support: the Microlepia clade, the northern Dennstaedtia clade, the Dennstaedtia globulifera clade, and the Dennstaedtia s.s. clade. Monachosorum was strongly resolved as sister to all the remaining genera of suborder Dennstaedtiineae. Based on the well resolved relationships among genera, the divergence between Monachosorum and other groups of suborder Dennstaedtiineae was estimated to have occurred in the Early Cretaceous, and all extant genera (and clades) in Dennstaedtiineae, were inferred to have diversified since the Late Oligocene. Conclusion This study supports reinstating a previously published family Monachosoraceae as a segregate from Dennstaedtiaceae, based on unique morphological evidence, the shady habitat, and the deep evolutionary divergence from its closest relatives.