Trojan-horse inspired nanoblaster: X-ray triggered spot attack on radio-resistant cancer through radiodynamic therapy.

Radiotherapy as a mainstay of in-depth cervical cancer (CC) treatment suffers from its radioresistance. Radiodynamic therapy (RDT) effectively reverses radio-resistance by generating reactive oxygen species (ROS) with deep tissue penetration. However, the photosensitizers stimulated by X-ray have high toxicity and energy attenuation. Therefore, X-ray responsive diselenide-bridged mesoporous silica nanoparticles (DMSNs) are designed, loading X-ray-activated photosensitizer acridine orange (AO) for spot blasting RDT like Trojan-horse against radio-resistance cervical cancer (R-CC). DMSNs can encapsulate a large amount of AO, in the tumor microenvironment (TME), which has a high concentration of hydrogen peroxide, X-ray radiation triggers the cleavage of diselenide bonds, leading to the degradation of DMSNs and the consequent release of AO directly at the tumor site. On the one hand, it solves the problems of rapid drug clearance, adverse distribution, and side effects caused by simple AO treatment. On the other hand, it fully utilizes the advantages of highly penetrating X-ray responsive RDT to enhance radiotherapy sensitivity. This approach results in ROS-induced mitochondria damage, inhibition of DNA damage repair, cell cycle arrest and promotion of cancer cell apoptosis in R-CC. The X-ray responsive DMSNs@AO hold considerable potential in overcoming obstacles for advanced RDT in the treatment of R-CC.

Manipulation of anisotropic Zhang-Rice exciton in NiPS3 by magnetic field.

The effect of external magnetic fields on the behavior of the Zhang-Rice exciton in NiPS3, which captures the physics of spin-orbital entanglement in 2D XY-type antiferromagnets, remains unclear. This study presents systematic study of angle-resolved and polarization-resolved magneto-optical photoluminescence spectra of NiPS3 in the Voigt geometry. We observed highly anisotropic, non-linear Zeeman splitting and polarization rotation of the Zhang-Rice exciton, which depends on the direction and intensity of the magnetic field and can be attributed to the spin-orbital coupling and field-induced spin reorientation. Furthermore, above the critical magnetic field, we detected additional splitting of the exciton peaks, indicating the coexistence of various orientations of Néel vector. This study characterizes orbital change of Zhang-Rice exciton and field-induced spin-reorientation phase transitions in a 2D hexagonal XY-type antiferromagnet, and it further demonstrates the continuous manipulation of the spin and polarization of the Zhang-Rice exciton.

Effects of cellulase treatment on properties of lignocellulose-based biochar.

As the most abundant renewable carbon source, lignocellulose holds potential as a raw material for biofuels and biochar. The components required for biofuel production differ from those for biochar, so combining processes can reduce costs. Biofuel preparation necessitates cellulase treatment of lignocellulose. This study examines the effects of various enzyme treatment conditions (dosage, time, temperature) on lignocellulose, focusing on the properties of biochar derived from it (BC-SR). A mathematical model was constructed to study the relationship between enzyme treatment conditions and BC-SR properties. BC-SR exhibited high adsorption selectivity for bisphenol A and outperformed untreated biochar in fixed-bed column experiments, demonstrating greater removal efficiency and structural integrity. This study provides insights into the impact of enzymatic treatment on biochar and offers a cost-effective method for producing stable, efficient biochar. Additionally, a highly persistent biochar can enter the carbon trading market as a carbon-neutral technology, further realizing economic and environmental benefits.

Four novel species of Pleurotheciaceae collected from freshwater habitats in Jiangxi Province, China.

During an investigation of fungal diversity from freshwater environments in different regions in Jiangxi Province, China, four interesting species were collected. Morphology coupled with combined gene analysis of an ITS, LSU, SSU, and rpb2 DNA sequence data showed that they belong to the family Pleurotheciaceae. Four new species, Pleurotheciella ganzhouensis, Pla. irregularis, Pla. verrucosa, and Pleurothecium jiangxiense are herein described. Pleurotheciella ganzhouensis is characterized by its capsule-shaped conidia and short conidiophores, while Pla. irregularis has amorphous conidiophores and 3-septate conidia. Pleurotheciella verrucosa has cylindrical or verrucolose conidiogenous cells, 1-septate, narrowly fusiform, meniscus or subclavate conidia. Pleurothecium jiangxiense characterized in having conidiogenous cells with dense cylindrical denticles and short conidiophores. Pleurothecium obovoideum was transferred to Neomonodictys based on phylogenetic evidence. All species are compared with other similar species and comprehensive descriptions, micrographs, and phylogenetic data are provided.

NFS1 as a Candidate Prognostic Biomarker for Gastric Cancer Correlated with Immune Infiltrates.

Background: Cysteine desulfurase (NFS1) is closely associated with the occurrence and development of human tumors, but its relationship with the prognosis and immunity of gastric cancer (GC) patients remains unclear. Methods: To study the relationship between NFS1 and GC, GC-related data of TCGA were downloaded and analyzed. At the same time, Tumor Immune Estimation Resource (TIMER) and Kaplan‒Meier Plotter were used for relevant online analysis. Clinical samples were collected for immunohistochemical testing to validate the results. Results: The mRNA and protein levels of NFS1 in GC tissues were significantly higher than those in normal tissues. In terms of the operating characteristic curve (ROC), the area under the curve (AUC) was 0.793, indicating that NFS1 had a high diagnostic value for GC. Further analysis showed that NFS1 expression was highly correlated with the depth of tumor invasion, lymph node metastasis, and tumor stage. Survival analysis showed that patients with high expression of NFS1 had a poorer prognosis, and NFS1 was an independent risk factor. Enrichment analysis by GO, KEGG, and GSEA showed that NFS1 was enriched in immune-related pathways. The expression of NFS1 was significantly positively correlated with the proportion of macrophages M0 and plasma cells but negatively correlated with the proportion of B cells memory, monocytes, and mast cells resting. In addition, NFS1 expression was significantly correlated with TMB levels and responses to immunotherapy. Conclusion: Our results suggest that NFS1 may be a potential biomarker for the diagnosis and prediction of prognosis and immunotherapy efficacy in GC.

Rapidly molded sodium alginate/soy protein adhesive hydrogel with 808-nm laser inhibition of infected wounds.

Infected wounds produce pus and heal slowly. To address this issue, we developed a rapid-setting SP/SA@BP-C hydrogel by combining sodium alginate (SA) and soy protein (SP) with black phosphorus (BP) grafted with clarithromycin (Cla) and incorporating Ca2+ for chelation. This hydrogel dressing exhibits excellent photothermal (PT) and photodynamic (PD) bacteriostatic effects without biotoxicity, making it suitable for treating infected wounds. Characterization confirmed its successful fabrication, and the bacteriostatic effect demonstrated over 99 % efficacy through the synergistic effects of PT, PD, and Cla. Cellular studies indicated nontoxicity and a promoting effect on cell proliferation (121.6 %). In the mouse-infected wound model, the hydrogel led to complete healing in 12 days, with good recovery of the skin's superficial dermal layer and appendages. Consequently, SP/SA@BP-C is a natural hydrogel dressing with promising properties.

N6-methyladenosine demethylase FTO regulates neuronal oxidative stress via YTHDC1-ATF3 axis in arsenic-induced cognitive dysfunction.

Excessive exposure to metals in daily life has been proposed as an environmental risk factor for neurological disorders. Oxidative stress is an inevitable stage involved in the neurotoxic effects induced by metals, nevertheless, the underlying mechanisms are still unclear. In this study, we used arsenic as a representative environmental heavy metal to induce neuronal oxidative stress and demonstrated that both in vitro and in vivo exposure to arsenic significantly increased the level of N6-methyladenosine (m6A) by down-regulating its demethylase FTO. Importantly, the results obtained from FTO transgenic mice and FTO overexpressed/knockout cells indicated that FTO likely regulated neuronal oxidative stress by modulating activating transcription factor 3 (ATF3) in a m6A-dependent manner. We also identified the specific m6A reader protein, YTHDC1, which interacted with ATF3 and thereby affecting its regulatory effects on oxidative stress. To further explore potential intervention strategies, cerebral metabolomics was conducted and we newly identified myo-inositol as a metabolite that exhibited potential in protecting against arsenic-induced oxidative stress and cognitive dysfunction. Overall, these findings provide new insights into the importance of the FTO-ATF3 signaling axis in neuronal oxidative stress from an m6A perspective, and highlight a beneficial metabolite that can counteract the oxidative stress induced by arsenic.

Perioperative toripalimab plus neoadjuvant chemotherapy might improve outcomes in resectable esophageal cancer: an interim analysis of a phase III randomized clinical trial.

BACKGROUND: In the era of immunotherapy, neoadjuvant immunochemotherapy (NAIC) for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC) is used clinically but lacks of high-level clinical evidence. This study aimed to compare the safety and long-term efficacy of NAIC followed by minimally invasive esophagectomy (MIE) with those of neoadjuvant chemotherapy (NAC) followed by MIE. METHODS: A prospective, single-center, open-label, randomized phase III clinical trial was conducted at Henan Cancer Hospital, Zhengzhou, China. Patients were randomly assigned to receive either neoadjuvant toripalimab (240 mg) plus paclitaxel (175 mg/m2) + cisplatin (75 mg/m2) (toripalimab group) or paclitaxel + cisplatin alone (chemotherapy group) every 3 weeks for 2 cycles. After surgery, the toripalimab group received toripalimab (240 mg every 3 weeks for up to 6 months). The primary endpoint was event-free survival (EFS). The pathological complete response (pCR) and overall survival (OS) were key secondary endpoints. Adverse events (AEs) and quality of life were also assessed. RESULTS: Between May 15, 2020 and August 13, 2021, 252 ESCC patients ranging from T1N1-3M0 to T2-3N0-3M0 were enrolled for interim analysis, with 127 in the toripalimab group and 125 in the chemotherapy group. The 1-year EFS rate was 77.9% in the toripalimab group compared to 64.3% in the chemotherapy group (hazard ratio [HR] = 0.62; 95% confidence interval [CI] = 0.39 to 1.00; P = 0.05). The 1-year OS rates were 94.1% and 83.0% in the toripalimab and chemotherapy groups, respectively (HR = 0.48; 95% CI = 0.24 to 0.97; P = 0.037). The patients in the toripalimab group had a higher pCR rate (18.6% vs. 4.6%; P = 0.001). The rates of postoperative Clavien-Dindo grade IIIb or higher morbidity were 9.8% in the toripalimab group and 6.8% in the chemotherapy group, with no significant difference observed (P = 0.460). The rates of grade 3 or 4 treatment-related AEs did not differ between the two groups (12.5% versus 12.4%). CONCLUSIONS: The interim results of this ongoing trial showed that in resectable ESCC, the addition of perioperative toripalimab to NAC is safe, may improve OS and might change the standard treatment in the future.

Multi-site phantomless bone mineral density from clinical quantitative computed tomography in males.

Volumetric bone mineral density (vBMD) is commonly assessed using QCT. Although standard vBMD calculation methods require phantom rods that may not be available, internal-reference phantomless (IPL) and direct measurements of Hounsfield units (HU) can be used to calculate vBMD in their absence. Yet, neither approach has been systemically assessed across skeletal sites, and HU need further validation as a vBMD proxy. This study evaluated the accuracy of phantomless methods, including IPL and regression-based phantomless (RPL) calibration using HU to calculate vBMD, compared to phantom-based (PB) methods. vBMD from QCT scans of 100 male post-mortem human subjects (PMHS) was calculated using site-specific PB calibration at multiple skeletal sites throughout the body. A development sample of 50/100 PMHS was used to determine site-specific reference material density for IPL calibration and RPL equations. Reference densities and equations from the development sample were used to calculate IPL and RPL vBMD on the remaining 50/100 PMHS for method validation. PB and IPL/RPL vBMD were not significantly different (p > .05). Univariate regressions between PB and IPL/RPL vBMD were universally significant (p < 0.05), except for IPL Rad-30 (p = 0.078), with a percent difference across all sites of 6.97% ± 5.95% and 5.22% ± 4.59% between PB and IPL/RPL vBMD, respectively. As vBMD increased, there were weaker relationships and larger differences between PB vBMD and IPL/RPL vBMD. IPL and RPL vBMD had strong relationships with PB vBMD across sites (R2 = 97.99, R2 = 99.17%, respectively), but larger residual differences were found for IPL vBMD. As the accuracy of IPL/RPL vBMD varied between sites, phantomless methods should be site-specific to provide values more comparable to PB vBMD. Overall, this study suggests that RPL calibration may better represent PB vBMD compared to IPL calibration, increases the utility of opportunistic QCT, and provides insight into bone quality and fracture risk.

Pulmonary Spindle Cell Carcinoma Mimicking Granulomatous Inflammation: A Rare Case Report and Brief Review of the Literature.

Background: Pulmonary spindle cell carcinoma (PSCC), a highly malignant tumor, often exhibits cell pleomorphism, a histopathological characteristic. Owing to its extremely low incidence, atypical imaging and clinical presentations, and insufficient awareness among clinicians, PSCC is often misdiagnosed, which results in delays in treatment. Herein, we reported a rare case of PSCC that was initially misdiagnosed as granulomatous inflammation. Case Presentation: A 66-year-old male visited a local hospital with symptoms such as cough and hemoptysis. A computed tomography (CT) scan of the chest revealed a mass in his right lung, and no mediastinal lymphadenopathy was observed. Bronchoscopy showed no major abnormalities, and the results of fine needle aspiration biopsy showed granulomatous inflammation. Even though the patient received anti-infection treatment, his symptoms did not improve markedly. After two months, a follow-up CT scan of the lung showed a noticeably enlarged mass accompanied by multiple instances of mediastinal lymphadenopathy in the upper lobe of the right lung. Consequently, he underwent a second CT-guided lung biopsy at our hospital. The pathology report indicated PSCC. Due to financial constraints, genetic testing was not performed. Given his poor overall physical condition, the patient was unable to undergo systemic chemotherapy and instead received palliative radiotherapy. The prescribed radiotherapy dose for the right upper lobe lung cancer and multiple metastatic lymph nodes was 60 Gy, administered in 30 fractions. Unfortunately, he failed to adhere to scheduled follow-ups and succumbed to the disease 6 months later, as confirmed during a telephone follow-up. Conclusion: PSCC is a rare but highly malignant lung cancer. Multiple pathological biopsies are necessary to accurately and promptly diagnose the disease, which is crucial for early treatment intervention as well as improving patient prognosis.

De novo Whole-Genome Assembly of the 10-Gigabase Fokienia Hodginsii Genome to Reveal Differential Epigenetic Events Between Callus and Xylem.

Fokienia hodginsii (F. hodginsii), belonging to the genus Fokienia of the Cupressaceae. F. hodginsii has significant application value due to its wood properties and great research value in evolutionary studies as a gymnosperm. However, the genome of F. hodginsii remains unknown due to the large size of gymnosperms genome. Pacific Bioscience sequencing, Hi-C mapping, whole-genome Bisulfite Sequencing (BS-Seq), long-read isoform sequencing (Iso-Seq), direct RNA sequencing (DRS), quantitative proteomics, and metabonomics analysis are employed to facilitate genome assembly, gene annotation, and investigation into epigenetic mechanisms. In this study, the 10G F. hodginsii genome is assembled into 11 chromosomes. Furthermore, 50 521 protein-coding genes are annotated and determined that 65% of F. hodginsii genome comprises repetitive sequences. It is discovered that transposable element (TE)-including introns is associated with higher expression. The DNA methylome of F. hodginsii reveals that xylem has a higher DNA methylation level compared to callus. Moreover, DRS reveals the significant alterations in RNA full-length ratio, which potentially associated with poly(A) length (PAL) and alternative polyadenylation (APA). Finally, the morphology measurement and metabonomics analysis revealed the difference of 14 cultivars. In summary, the genomes and epigenetics datasets provide a molecular basis for callus formation in the gymnosperm family.

Relationship between postoperative rehabilitation style, gastrointestinal function, and inflammatory factor levels in children with intussusception.

BACKGROUND: Intussusception occurs in children and progresses rapidly. If not treated in time, it may lead to secondary complications such as intestinal perforation, which affect the quality of life and health of children. Surgery is the most common clinical treatment and has a good effect. However, the postoperative prognosis of children with intussusception has a correlation with the postoperative rehabilitation method. Therefore, in this study, we explored the relationship between postoperative rehabilitation, gastrointestinal function, and the expression of inflammatory factors in children with intussusception. AIM: To explore the relationship between postoperative rehabilitation, gastrointestinal function, and inflammatory factor levels in children with intussusception. METHODS: The medical records of 18 children who were admitted to our hospital for intussusception surgery between October 2022 and May 2024 were retrospectively reviewed. The patients were divided into the routine nursing group (n = 6) and rehabilitation training group (n = 12) according to the postoperative rehabilitation method. The general data, gastrointestinal function, and inflammatory factor levels of the two groups were statistically analyzed. Pearson correlation analysis of gastrointestinal function, inflammatory factors, and postoperative rehabilitation was performed. RESULTS: We found no significant intergroup differences in sex, age, or disease course (P > 0.05). The times to first defecation, bowel sound recovery, and anal exhaust were shorter and inflammatory factor levels were lower in the rehabilitation training group than in the routine nursing group (P < 0.05). Pearson correlation analysis showed that gastrin and motilin levels were positively correlated with postoperative rehabilitation (P < 0.05). Interleukin (IL)-2, IL-4, IL-6, IL-10, high-sensitivity C-reactive protein, and tumor necrosis factor-α levels were negatively correlated with postoperative rehabilitation (P < 0.05). Gastrointestinal function was positively correlated (P < 0.05), and levels of inflammatory factors were negatively correlated with postoperative recovery time (P < 0.05). CONCLUSION: We found a positive correlation between gastrointestinal function and postoperative rehabilitation training, and a negative correlation between inflammatory factor levels and rehabilitation training in children with intussusception.

Facet Engineering Boosts Interfacial Compatibility of Inorganic-Polymer Composites.

The interfacial compatibility between inorganic particles and polymer is crucial for ensuring high performance of composites. Current efforts to improve interfacial compatibility preferentially rely on organic modification of inorganic particles, leading to their complex process, high costs, and short lifespans due to aging and decomposition of organic modifiers. However, the fabrication of inorganic particles free from organic modification that is highly compatible in polymer still remains a great challenge. Herein, a novel facet-engineered inorganic particle that exhibit high compatibility with widely used polymer interface without organic modification is reported. Theoretical calculations and experimental results show that (020) and (102) facets of inorganic particles modulate local coordination environment of Ca atoms, which in turn regulate d-orbital electron density of Ca atoms and electron transfer paths at interfaces between polymer and inorganic particles. This difference alters the molecular diffusion, orientation of molecular chains on surface of inorganic particles, further modulating interfacial compatibility of composites. Surprisingly, the facet-engineered inorganic particles show exceptional mechanical properties, especially for tensile strain at break, which increases by 395%, far superior to state-of-the-art composites counterparts. Thus, the method can offer a more benign approach to the general production of high-performance and low-cost polymer-inorganic composites for diverse potential applications.

A pathology foundation model for cancer diagnosis and prognosis prediction.

Histopathology image evaluation is indispensable for cancer diagnoses and subtype classification. Standard artificial intelligence methods for histopathology image analyses have focused on optimizing specialized models for each diagnostic task1,2. Although such methods have achieved some success, they often have limited generalizability to images generated by different digitization protocols or samples collected from different populations3. Here, to address this challenge, we devised the Clinical Histopathology Imaging Evaluation Foundation (CHIEF) model, a general-purpose weakly supervised machine learning framework to extract pathology imaging features for systematic cancer evaluation. CHIEF leverages two complementary pretraining methods to extract diverse pathology representations: unsupervised pretraining for tile-level feature identification and weakly supervised pretraining for whole-slide pattern recognition. We developed CHIEF using 60,530 whole-slide images spanning 19 anatomical sites. Through pretraining on 44 terabytes of high-resolution pathology imaging datasets, CHIEF extracted microscopic representations useful for cancer cell detection, tumour origin identification, molecular profile characterization and prognostic prediction. We successfully validated CHIEF using 19,491 whole-slide images from 32 independent slide sets collected from 24 hospitals and cohorts internationally. Overall, CHIEF outperformed the state-of-the-art deep learning methods by up to 36.1%, showing its ability to address domain shifts observed in samples from diverse populations and processed by different slide preparation methods. CHIEF provides a generalizable foundation for efficient digital pathology evaluation for patients with cancer.

Oroxylin A alleviates myocardial ischemia-reperfusion injury by quelling ferroptosis via activating the DUSP10/MAPK-Nrf2 pathway.

Reperfusion therapy is the primary treatment strategy for acute myocardial infarction (AMI). Paradoxically, it can lead to myocardial damage, namely myocardial ischemia/reperfusion injury (MIRI). This study explored whether oroxylin A (OA) protects the myocardium after MIRI by inhibiting ferroptosis and the underlying mechanism. In vivo, we established an MIRI model to investigate the protective effect of OA. In vitro, H9C2 cells were used to explore the regulation of ferroptosis by OA through immunofluorescence staining, western blotting, assay kits, etc. Additionally, RNA sequencing analysis (RNA-seq) and network pharmacology analyses were conducted to elucidate the molecular mechanisms. Our results showed that MIRI caused cardiac structural and functional damage in rats. MIRI promoted ferroptosis, which was consistently observed in vitro. However, pretreatment with OA reversed these effects. The mitogen-activated protein kinases (MAPK) signaling pathway participated in the MIRI process, with dual-specificity phosphatase 10 (DUSP10) found to regulate it. Further confirmation was provided by knocking down DUSP10 using small interfering RNA (siRNA), demonstrating the activation of the DUSP10/MAPK-Nrf2 pathway by OA to protect H9C2 cells from ferroptosis. Our research has demonstrated the mitigating effect of OA on MIRI and the improvement of myocardial function for the first time. The inhibition of ferroptosis has been identified as one of the mechanisms through which OA exerts its myocardial protective effects. Moreover, we have first unveiled that DUSP10 serves as an upstream target involved in mediating ferroptosis, and the regulation of the DUSP10/MAPK-Nrf2 pathway by OA is crucial in inhibiting ferroptosis to protect the myocardium.

Observational and genetic evidence disagree on the association between loneliness and risk of multiple diseases.

Loneliness-the subjective experience of social disconnection-is now widely regarded as a health risk factor. However, whether the associations between loneliness and multiple diseases are consistent with causal effects remains largely unexplored. Here we combined behavioural, genetic and hospitalization data from the UK Biobank to examine the associations of loneliness with a wide range of non-overlapping diseases. During a median 12.2-year follow-up, loneliness was associated with greater risks in 13 of 14 disease categories and 30 of 56 individual diseases considered. Of the 30 diseases significantly associated with loneliness, 26 had genetic data available for Mendelian randomization (MR) analyses. After Benjamini‒Hochberg correction and multiple sensitivity analyses within the MR framework, non-causal associations were identified between genetic liability to loneliness and 20 out of the 26 specific diseases, including cardiovascular diseases, type 2 diabetes mellitus, obesity, chronic liver diseases, chronic kidney disease, most neurological diseases and the other common diseases. Genetic liability to loneliness was only potentially causally associated with the remaining six diseases. Socioeconomic factors, health behaviours, baseline depressive symptoms and comorbidities largely explained the associations between loneliness and diseases. Overall, our study revealed a dissociation between observational and genetic evidence regarding the associations of loneliness with multiple diseases. These findings suggest that loneliness may serve as a potential surrogate marker rather than a causal risk factor for most diseases tested here.

Biological and genomic characterization of a polyvalent phage PSH-1 against multidrug-resistant Salmonella Enteritidis.

BACKGROUND: Bacteriophage has been renewed attention as a new antibacterial agent due to the limitations of antibiotic treatment. Bacteriophages are generally thought to be highly host specific and even strain specific, but a small number of polyvalent bacteriophages have been found to infect bacteria of different genera. RESULTS: In this study, a virulent lytic bacteriophage (named Salmonella phage PSH-1) of Salmonella Enteritidis was isolated from the sewage samples of a large-scale pig farm, PSH-1 demonstrated lytic activity against four multidrug-resistant Salmonella Enteritidis isolates and Escherichia coli, and then its biological characteristics, genome and bacteriostatic ability were investigated. The results showed that the initial titer of PSH-1 was 1.15 × 1010 PFU/mL and the optimal multiplicity of infection (MOI) was 0.01, PSH-1 has stable activity in the range of pH 3.0-11.0. One-step growth curve showed that its latent period was 20 min, burst time was 80 min, and the burst was 495 particles. The whole-genome sequencing results revealed phage PSH-1 had a linear dsDNA with 48,466 bp length. The G/C content was 45.33%. Non-coding RNA genes and virulence factors were not found. Eighty- five open reading frames (ORFs) were identified after online annotation. By tests, the use of phage could succeed in controlling the artificial Salmonella contamination in milk at a range of temperatures. CONCLUSIONS: This study reports a novel Salmonella Enteritidis phage PSH-1, which has a robust lytic ability, no virulence factors, and good stability. The characterization and genomic analysis of PSH-1 will develop our understanding of phage biology and diversity and provide a potential arsenal for controlling of salmonellosis.

Gut microbiome pattern impacts treatment response in primary biliary cholangitis.

BACKGROUND: Primary biliary cholangitis (PBC) is a progressive autoimmune liver disease. An inadequate response to ursodeoxycholic acid (UDCA) poses a high risk of progression toward end-stage liver disease. Gut dysbiosis has been implicated in PBC. Here, we aimed to investigate microbial signatures that permit risk stratification and provide mechanistic insights into novel therapies for PBC. METHODS: We prospectively recruited UDCA treatment-naive patients with PBC and performed metagenomic sequencing and metabolomic profiling using stool and serum samples obtained before (n = 132) and after (n = 59) treatment. PBC microbiome subtypes were identified using unsupervised machine learning methods and validated in two independent cohorts. FINDINGS: PBC baseline metagenomes clustered into two community subtypes characterized by varying abundances of Clostridia taxa. Compared with Clostridialow microbiomes, Clostridiahigh microbiomes were more similar to healthy controls. Notably, patients in the Clostridialow subtype exhibited a 2-fold higher UDCA non-response rate compared to those in the Clostridiahigh subtype (41% vs. 20%, p = 0.015). Integrative analysis of metagenomic and metabolomic data revealed divergent functional modules and metabolic activities between the two metacommunities. In particular, anaerobic fermentation and the production of bioactive metabolites, including tryptophan derivatives and secondary bile acids, crucial for immune regulation and gut barrier maintenance, were markedly diminished in the Clostridialow subtype. Moreover, UDCA administration reconfigured the fecal microbial and metabolic profiles only in the Clostridiahigh group. Importantly, the microbiome subtypes and their associations with UDCA response were reproducible in two independent treatment-naive PBC cohorts. CONCLUSIONS: Characterizing baseline microbiota patterns may enable the prediction of treatment outcomes in PBC and facilitate personalized treatment strategies. FUNDING: This research was mainly supported by the National Natural Science Foundation of China.