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Burkholderia semiarida has only been reported as a plant pathogen causing onion sour skin (1). The Burkholderia genus encompasses >120 bacterial species that are typically reported to inhabit soil and [...]

Abstract Quantum effects in photosynthetic energy transport in nature, especially for the typical Fenna-Matthews-Olson (FMO) complexes, are extensively studied in quantum biology. Such energy transport processes can be investigated as open quantum systems that blend the quantum coherence and environmental noise, and have been experimentally simulated on a few quantum devices. However, the existing experiments always lack a solid quantum simulation for the FMO energy transport due to their constraints to map a variety of issues in actual FMO complexes that have rich biological meanings. Here we successfully map the full coupling profile of the seven-site FMO structure by comprehensive characterisation and precise control of the evanescent coupling of the three-dimensional waveguide array. By applying a stochastic dynamical modulation on each waveguide, we introduce the base site energy and the dephasing term in coloured noise to faithfully simulate the power spectral density of the FMO complexes. We show our photonic model well interprets the phenomena including reorganisation energy, vibrational assistance, exciton transfer and energy localisation. We further experimentally demonstrate the existence of an optimal transport efficiency at certain dephasing strength, providing a window to closely investigate environment-assisted quantum transport.

Background: collagen type I is a fundamental composition of extracellular matrix. Typically it exists in the form of a heterotrimer, consisting of two α1 chains encoded by COL1A1 and one α2 chain encoded by COL1A2. However, in cancer a homotrimeric form of collagen type I comprises three α1 chains encoded by COL1A1 was founded. There is still a lack of transcriptional and histologic methods for detecting homotrimeric collagen type I. Furthermore, a comprehensive analysis of the pan-cancer distribution pattern and clinical relevance of homotrimeric collagen type I is conspicuously absent. Method: Using transcriptional and immunoflourance method, we established homocol signature, which is able to transcriptionally and histologically detect homotrimeric collagen type I. We investigated the diagnostic and prognostic potential of homocol as a novel cancer biomarker in a pan-cancer cohort. Furthermore, we assessed its association with clinical manifestations in a liver cancer cohort undergoing treatment at our institute. Result: Homotrimer Collagen Type I is predominantly expressed by cancer cells and is linked to several critical cancer hallmarks, particularly inflammatory response and proliferation. Survival analyses have indicated that a high Homocol expression is correlated with poor outcomes in most types of cancer studied. In terms of cancer detection, Homocol demonstrated strong performance in Receiver Operating Characteristic (ROC) analysis, with an Area Under Curve (AUC) of 0.83 for pan-cancer detection and between 0.72 and 0.99 for individual cancers.In cohorts undergoing PD1 treatment, we noted a higher presence of Homocol in the response group. In a Hepatocellular Carcinoma (HCC) clinical set, high Homocol expression was associated with an increased formation of intra-tumor tertiary lymphoid structures (TLS), larger tumor sizes, more advanced Barcelona Clinic Liver Cancer (BCLC) stages, higher microvascular invasion (MVI) grades, absence of a capsule, and an enriched para-tumor collagen presence. Conclusion: our research has led to the development of a novel gene signature that facilitates the detection of Homotrimer Collagen Type I. This may greatly assist efforts in cancer detection, prognosis, treatment response prediction, and further research into Homotrimer Collagen Type I.

Abstract Background Hepatocellular carcinoma (HCC) is closely associatedwith chronic liver diseases, particularly liver cirrhosis, which has an altered extracellular matrix (ECM) composition. The influence and its mechanism of the cirrhotic-ECM on the response of HCC to immune checkpoint inhibitor (ICI) remains less clarified. Methods In silico, proteomic and pathological assessment of alteration of cirrhotic-ECM were applied in clinical cohort. Multiple pre-clinical models with ECM manipulation were used to evaluate cirrhotic-ECM’s effect on ICI treatment. In silico, flow cytometry and IHC were applied to explore how cirrhotic-ECM affect HCC microenvironment. In vitro and in vivo experiments were carried out to identify the mechanism of how cirrhotic-ECM undermined ICI treatment. Results We defined “a pro-tumor cirrhotic-ECM” which was featured as the up-regulation of collagen type 1 (Col1). Cirrhotic-ECM/Col1 was closely related to impaired T cell function and limited anti PD-1 (aPD-1) response of HCC patients from the TCGA pan cancer cohort and the authors’ institution, as well as in multiple pre-clinical models. Mechanically, cirrhotic-ECM/Col1 orchestrated an immunosuppressive microenvironment (TME) by triggering Col1-DDR1-NFκB-CXCL8 axis, which initiated neutrophil extracellular traps (NETs) formation to shield HCC cells from attacking T cells and impede approaching T cells. Nilotinib, an inhibitor of DDR1, reversed the neutrophils/NETs dominant TME and efficiently enhanced the response of HCC to aPD-1. Conclusions Cirrhotic-ECM modulated a NETs enriched TME in HCC, produced an immune suppressive TME and weakened ICI efficiency. Col1 receptor DDR1 could be a potential target synergically used with ICI to overcome ECM mediated ICI resistance. These provide a mechanical insight and novel strategy to overcome the ICI resistance of HCC.

Background COVID-19 carriers experience psychological stresses and mental health issues such as varying degrees of stigma. The Social Impact Scale (SIS) can be used to measure the stigmatisation of COVID-19 carriers who experience such problems. Aims To evaluate the reliability and validity of the Chinese version of the SIS, and the association between stigma and depression among asymptomatic COVID-19 carriers in Shanghai, China. Method A total of 1283 asymptomatic COVID-19 carriers from Shanghai Ruijin Jiahe Fangcang Shelter Hospital were recruited, with a mean age of 39.64 ± 11.14 years (59.6% male). Participants completed questionnaires, including baseline information and psychological measurements, the SIS and Self-Rating Depression Scale. The psychometrics of the SIS and its association with depression were examined through exploratory factor analysis, confirmatory factor analysis and receiver operating characteristic analysis. Results The average participant SIS score was 42.66 ± 14.61 (range: 24–96) years. Analyses suggested the model had four factors: social rejection, financial insecurity, internalised shame and social isolation. The model fit statistics of the four-factor SIS were 0.913 for the comparative fit index, 0.902 for the Tucker–Lewis index and 0.088 for root-mean-square error of approximation. Standard estimated factor loadings ranged from 0.509 to 0.836. After controlling for demographic characteristics, the total score of the 23-item SIS predicted depression (odds ratio: 1.087, 95% CI 1.061–1.115; area under the curve: 0.84, 95% CI 0.788–0.892). Conclusions The Chinese version of the SIS showed good psychometric properties and can be used to assess the level of perceived stigma experienced by asymptomatic COVID-19 carriers.

Abstract Foundation models, often pre-trained with large-scale data, have achieved paramount success in jump-starting various vision and language applications. Recent advances further enable adapting foundation models in downstream tasks efficiently using only a few training samples, e.g., in-context learning. Yet, the application of such learning paradigms in medical image analysis remains scarce due to the shortage of publicly accessible data and benchmarks. In this paper, we aim at approaches adapting the foundation models for medical image classification and present a novel dataset and benchmark for the evaluation, i.e., examining the overall performance of accommodating the large-scale foundation models downstream on a set of diverse real-world clinical tasks. We collect five sets of medical imaging data from multiple institutes targeting a variety of real-world clinical tasks (22,349 images in total), i.e., thoracic diseases screening in X-rays, pathological lesion tissue screening, lesion detection in endoscopy images, neonatal jaundice evaluation, and diabetic retinopathy grading. Results of multiple baseline methods are demonstrated using the proposed dataset from both accuracy and cost-effective perspectives.

Sensorineural hearing loss (SNHL), a highly prevalent sensory impairment, results from a multifaceted interaction of genetic and environmental factors. As we continually gain insights into the molecular basis of auditory development and the growing compendium of deafness genes identified, research on gene therapy for SNHL has significantly deepened. Adeno-associated virus (AAV), considered a relatively secure vector for gene therapy in clinical trials, can deliver various transgenes based on gene therapy strategies such as gene replacement, gene silencing, gene editing, or gene addition to alleviate diverse types of SNHL. This review delved into the preclinical advances in AAV-based gene therapy for SNHL, spanning hereditary and acquired types. Particular focus is placed on the dual-AAV construction method and its application, the vector delivery route of mouse inner ear models (local, systemic, fetal, and cerebrospinal fluid administration), and the significant considerations in transforming from AAV-based animal model inner ear gene therapy to clinical implementation.

Abstract Objectives This study explores whether feelings of defeat (i.e., a sense of failed struggle and losing rank; referred to as defeat for simplicity) mediated the effect of work stress on depression/anxiety, the effect of interpersonal needs on depression/anxiety for Chinese industrial workers, and the possible moderating role of social support. Method A cross-sectional study was conducted in Shenzhen, China in 2019, in total, 2023 industrial workers (of 2700 invited; response rate = 75%) completed a self-administered survey consisted of Job Stress Scale, Interpersonal Needs Questionnaire, Defeat Scale, Centre for Epidemiological Studies Depression Scale, Generalized Anxiety Disorder Scale, two face-valid questions for social support, as well as sociodemographic information. Moderated mediation model was tested and loop plots were applied to probe into the conditional effects of work and interpersonal stress on depression and anxiety symptoms. Result Both the direct and indirect effect of work stress on depression and anxiety through defeat were significant (Work stress→ Depression: B = 0.035, p

Objective: To study the laxative effect of Lactiplantibacillus plantarum P9 on functional constipation in mice and its effect on the gut microbiota. Methods: One hundred Balb/c male mice were randomly divided into five groups of 20 mice each: blank, model, low-dose P9 (dried bacterial powder with a viable cell count of 2.0 × 1011 CFU/g, 0.42 mg/(kg mb·d)), medium-dose P9 (0.84 mg/(kg mb·d)), and high-dose P9 (2.5 mg/(kg mb·d)). The mice in the three dose groups were gavaged with L. plantarum P9 suspension in sterile deionized water at 10 mL/(kg mb·d) for 15 days, while those in the blank and model groups were gavaged with an equal volume of distilled water. On day 16 of the experiment, loperamide at 4 mg/(kg mb·d) was applied by gavage to induce functional constipation in mice. Ten mice with constipation were randomly selected for defecation test, where the time of the first black stool and the weight of black stool at 6 h were measured. The remaining 10 mice were measured for the rate of ink advancement, and the composition of the cecal flora was determined by 16S rRNA high-throughput sequencing. After the end of the defecation test, the remaining mice in the model and P9 intervention groups were continuously gavaged with loperamide at 4 mg/(kg mb·d) to establish a mouse model of functional constipation, while those in the blank group was given an equal volume of distilled water. The mice in the P9 intervention groups were administered with L. plantarum P9 at 1 h after modeling, whereas those in the blank and model groups were given an equal volume of distilled water by gavage for six days. The histopathological changes of the colon were observed by hematoxylin-eosin (HE) staining, and serum motilin (MTL), gastrin (GAS), acetylcholine (AchE), and nitric oxide (NO) levels were determined. Results: Compared with the model group, the medium dose of L. plantarum P9 significantly shortened the time the first black stool in mice with functional constipation (P < 0.05), and the medium and high doses of L. plantarum P9 significantly increased the volume of black stool excretion at 6 h (P < 0.01 and P < 0.001). The low, medium and high doses of L. plantarum P9 significantly increased the rate of ink advancement in mice (P < 0.01, P < 0.05, and P < 0.001), and augmented the serum levels of MTL, GAS and AchE. The low dose of L. plantarum P9 significantly increased the level of GAS (P < 0.001), the high dose of L. plantarum P9 significantly increased the level of MTL (P < 0.01), the low and medium doses of L. plantarum P9 significantly increased the level of AchE (P < 0.05), and the low and medium doses of L. plantarum P9 significantly decreased the level of NO (P < 0.05). The damaged intestinal barrier was repaired and the richness and diversity of the gut microbiota were significantly increased at all doses of L. plantarum P9. Conclusion: L. plantarum P9 has a good laxative effect, and its mechanism may be related to improving intestinal motility, regulating gastrointestinal serum neurotransmitters and increasing the richness and diversity of the gut microbiota.

Abstract Objective To identify DNA methylation and clinical features, and to construct machine learning classifiers to assign the patients with major depressive disorder (MDD) into responders and non-responders after a 2-week treatment into responders and non-responders. Method Han Chinese patients (291 in total) with MDD comprised the study population. Datasets contained demographic information, environment stress factors, and the methylation levels of 38 methylated sites of tryptophan hydroxylase 2 (TPH2) genes in peripheral blood samples. Recursive Feature Elimination (RFE) was employed to select features. Five classification algorithms (logistic regression, classification and regression trees, support vector machine, logitboost and random forests) were used to establish the models. Performance metrics (AUC, F-Measure, G-Mean, accuracy, sensitivity, specificity, positive predictive value and negative predictive value) were computed with 5-fold-cross-validation. Variable importance was evaluated by random forest algorithm. Result RF with RFE outperformed the other models in our samples based on the demographic information and clinical features (AUC = 61.2%, 95%CI: 60.1-62.4%) / TPH2 CpGs features (AUC = 66.6%, 95%CI: 65.4-67.8%) / both clinical and TPH2 CpGs features (AUC = 72.9%, 95%CI: 71.8-74.0%). Conclusion The effects of TPH2 on the early-stage antidepressant response were explored by machine learning algorithms. On the basis of the baseline depression severity and TPH2 CpG sites, machine learning approaches can enhance our ability to predict the early-stage antidepressant response. Some potentially important predictors (e.g., TPH2-10-60 (rs2129575), TPH2-2-163 (rs11178998), age of first onset, age) in early-stage treatment response could be utilized in future fundamental research, drug development and clinical practice.

Abstract Several groups of bacteria have complex life cycles involving cellular differentiation and multicellular structures. For example, actinobacteria of the genus Streptomyces form multicellular vegetative hyphae, aerial hyphae, and spores. However, similar life cycles have not yet been described for archaea. Here, we show that several haloarchaea of the family Halobacteriaceae display a life cycle resembling that of Streptomyces bacteria. Strain YIM 93972 (isolated from a salt marsh) undergoes cellular differentiation into mycelia and spores. Other closely related strains are also able to form mycelia, and comparative genomic analyses point to gene signatures (apparent gain or loss of certain genes) that are shared by members of this clade within the Halobacteriaceae. Genomic, transcriptomic and proteomic analyses of non-differentiating mutants suggest that a Cdc48-family ATPase might be involved in cellular differentiation in strain YIM 93972. Additionally, a gene encoding a putative oligopeptide transporter from YIM 93972 can restore the ability to form hyphae in a Streptomyces coelicolor mutant that carries a deletion in a homologous gene cluster (bldKA-bldKE), suggesting functional equivalence. We propose strain YIM 93972 as representative of a new species in a new genus within the family Halobacteriaceae, for which the name Actinoarchaeum halophilum gen. nov., sp. nov. is herewith proposed. Our demonstration of a complex life cycle in a group of haloarchaea adds a new dimension to our understanding of the biological diversity and environmental adaptation of archaea.

BackgroundOsteoporosis represents a significant health concern as a widespread metabolic bone condition. In this study, we aim to utilize path analysis to examine the intricate relationships among demographic information, Health Belief Model (HBM) constructs and osteoporosis preventive behavior among Shanghai residents over 40 years of age.MethodsA multi-center population study was conducted in 20 volunteer communities in Shanghai, China. Out of the 2,000 participants who volunteered, 1,903 completed the field survey.Results56.0% of participants were females. Their mean age was 63.64 ± 10.30 years. The self-efficacy score among females (42.27 ± 15.82) was also significantly higher than that among males (40.68 ± 15.20). in the pathway analysis. In the path analysis preventive behaviors were significantly predicted by education (β = 0.082, p < 0.001), knowledge (β = 0.132, p < 0.001) and self-efficacy (β = 0.392, p < 0.001).ConclusionsThis study highlights the importance of gender, education, knowledge and self-efficacy in promoting OP preventive behaviors using the Health Belief Model. The findings emphasize the need for tailored interventions to address the specific needs of different demographic groups.

PurposeEndothelial dysfunction, which was associated with chronic hypothyroidism, was an early event in atherosclerosis. Whether short-term hypothyroidism following thyroxine withdrawal during radioiodine (RAI) therapy was associated with endothelial dysfunction in patients with differentiated thyroid cancer (DTC) was unclear. Aim of the study was to assess whether short-term hypothyroidism could impair endothelial function and the accompanied metabolic changes in the whole process of RAI therapy.MethodsWe recruited fifty-one patients who underwent total thyroidectomy surgery and would accept RAI therapy for DTC. We analyzed thyroid function, endothelial function and serum lipids levels of the patients at three time points: the day before thyroxine withdrawal(P1), the day before 131I administration(P2) and 4-6 weeks after RAI therapy(P3). A high-resolution ultrasound named flow-mediated dilation (FMD) was used to measure endothelial function of the patients.ResultsWe analyzed the changes of FMD, thyroid function and lipids at three time points. FMD(P2) decreased significantly compared to FMD(P1) (P1vsP2, 8.05 ± 1.55vs 7.26 ± 1.50, p

IntroductionThe diversity, nitrogen-fixing capacity and heavy metal tolerance of culturable rhizobia in symbiotic relationship with Pongamia pinnata surviving in vanadium (V) - titanium (Ti) magnetite (VTM) tailings is still unknown, and the rhizobia isolates from the extreme barren VTM tailings contaminated with a variety of metals would provide available rhizobia resources for bioremediation.MethodsP. pinnata plants were cultivated in pots containing the VTM tailings until root nodules formed, and then culturable rhizobia were isolated from root nodules. The diversity, nitrogen-fixing capacity and heavy metal tolerance of rhizobia were performed.ResultsAmong 57 rhizobia isolated from these nodules, only twenty strains showed different levels of tolerance to copper (Cu), nickel (Ni), manganese (Mn) and zinc (Zn), especially strains PP1 and PP76 showing high tolerance against these four heavy metals. Based on the phylogenetic analysis of 16S rRNA and four house-keeping genes (atpD, recA, rpoB, glnII), twelve isolates were identified as Bradyrhizobium pachyrhizi, four as Ochrobactrum anthropic, three as Rhizobium selenitireducens and one as Rhizobium pisi. Some rhizobia isolates showed a high nitrogen-fixing capacity and promoted P. pinnata growth by increasing nitrogen content by 10%-145% in aboveground plant part and 13%-79% in the root. R. pachyrhizi PP1 showed the strongest capacity of nitrogen fixation, plant growth promotion and resistance to heavy metals, which provided effective rhizobia strains for bioremediation of VTM tailings or other contaminated soils. This study demonstrated that there are at least three genera of culturable rhizobia in symbiosis with P. pinnata in VTM tailings.DiscussionAbundant culturable rhizobia with the capacity of nitrogen fixation, plant growth promotion and resistance to heavy metals survived in VTM tailings, indicating more valuable functional microbes could be isolated from extreme soil environments such as VTM tailings.

Summary: Alveolar epithelial type 2 (AT2) cells harbor the facultative progenitor capacity in the lung alveolus to drive regeneration after lung injury. Using single-cell transcriptomics, software-guided segmentation of tissue damage, and in vivo mouse lineage tracing, we identified the grainyhead transcription factor cellular promoter 2-like 1 (Tfcp2l1) as a regulator of this regenerative process. Tfcp2l1 loss in adult AT2 cells inhibits self-renewal and enhances AT2-AT1 differentiation during tissue regeneration. Conversely, Tfcp2l1 blunts the proliferative response to inflammatory signaling during the early acute injury phase. Tfcp2l1 temporally regulates AT2 self-renewal and differentiation in alveolar regions undergoing active regeneration. Single-cell transcriptomics and lineage tracing reveal that Tfcp2l1 regulates cell fate dynamics across the AT2-AT1 differentiation and restricts the inflammatory program in murine AT2 cells. Organoid modeling shows that Tfcp2l1 regulation of interleukin-1 (IL-1) receptor expression controlled these cell fate dynamics. These findings highlight the critical role Tfcp2l1 plays in balancing epithelial cell self-renewal and differentiation during alveolar regeneration.