Unified Model for Children's Brain Image Segmentation with Co-Registration Framework Guided by Longitudinal MRI.

Accurate segmentation of brain structures is crucial for analyzing longitudinal changes in children's brains. However, existing methods are mostly based on models established at a single time-point due to difficulty in obtaining annotated data and dynamic variation of tissue intensity. The main problem with such approaches is that, when conducting longitudinal analysis, images from different time points are segmented by different models, leading to significant variation in estimating development trends. In this paper, we propose a novel unified model with co-registration framework to segment children's brain images covering neonates to preschoolers, which is formulated as two stages. First, to overcome the shortage of annotated data, we propose building gold-standard segmentation with co-registration framework guided by longitudinal data. Second, we construct a unified segmentation model tailored to brain images at 0-6 years old through the introduction of a convolutional network (named SE-VB-Net), which combines our previously proposed VB-Net with Squeeze-and-Excitation (SE) block. Moreover, different from existing methods that only require both T1- and T2-weighted MR images as inputs, our designed model also allows a single T1-weighted MR image as input. The proposed method is evaluated on the main dataset (320 longitudinal subjects with average 2 time-points) and two external datasets (10 cases with 6-month-old and 40 cases with 20-45 weeks, respectively). Results demonstrate that our proposed method achieves a high performance (>92%), even over a single time-point. This means that it is suitable for brain image analysis with large appearance variation, and largely broadens the application scenarios.

Role of C/EBP Homologous Protein in Vascular Stenosis After Carotid Artery Injury.

The study aims to explore the fluctuating expression of C/EBP Homologous Protein (CHOP) following rat carotid artery injury and its central role in vascular stenosis. Using in vivo rat carotid artery injury models and in vitro ischemia and hypoxia cell models employing human aortic endothelial cells (HAECs) and vascular smooth muscle cells (T/G HA-VSMCs), a comprehensive investigative framework was established. Histological analysis confirmed intimal hyperplasia in rat models. CHOP expression in vascular tissues was assessed using Western blot and immunohistochemical staining, and its presence in HAECs and T/G HA-VSMCs was determined through RT-PCR and Western blot. The study evaluated HAEC apoptosis, inflammatory cytokine secretion, cell proliferation, and T/G HA-VSMCs migration through Western blot, ELISA, CCK8, and Transwell migration assays. The rat carotid artery injury model revealed substantial fibrous plaque formation and vascular stenosis, resulting in an increased intimal area and plaque-to-lumen area ratio. Notably, CHOP is markedly elevated in vessels of the carotid artery injury model compared to normal vessels. Atorvastatin effectively mitigated vascular stenosis and suppresses CHOP protein expression. In HAECs, ischemia and hypoxia-induced CHOP upregulation, along with heightened TNFα, IL-6, caspase3, and caspase8 levels, while reducing cell proliferation. Atorvastatin demonstrated a dose-dependent suppression of CHOP expression in HAECs. Downregulation of CHOP or atorvastatin treatment led to reduced IL-6 and TNFα secretion, coupled with augmented cell proliferation. Similarly, ischemia and hypoxia conditions increased CHOP expression in T/G HA-VSMCs, which was concentration-dependently inhibited by atorvastatin. Furthermore, significantly increased MMP-9 and MMP-2 concentrations in the cell culture supernatant correlated with enhanced T/G HA-VSMCs migration. However, interventions targeting CHOP downregulation and atorvastatin usage curtailed MMP-9 and MMP-2 secretion and suppressed cell migration. In conclusion, CHOP plays a crucial role in endothelial injury, proliferation, and VSMCs migration during carotid artery injury, serving as a pivotal regulator in post-injury fibrous plaque formation and vascular remodeling. Statins emerge as protectors of endothelial cells, restraining VSMCs migration by modulating CHOP expression.

Salmonellosis outbreak archive in China: data collection and assembly.

Infectious disease outbreaks transcend the medical and public health realms, triggering widespread panic and impeding socio-economic development. Considering that self-limiting diarrhoea of sporadic cases is usually underreported, the Salmonella outbreak (SO) study offers a unique opportunity for source tracing, spatiotemporal correlation, and outbreak prediction. To summarize the pattern of SO and estimate observational epidemiological indicators, 1,134 qualitative reports screened from 1949 to 2023 were included in the systematic review dataset, which contained a 506-study meta-analysis dataset. In addition to the dataset comprising over 50 columns with a total of 46,494 entries eligible for inclusion in systematic reviews or input into prediction models, we also provide initial literature collection datasets and datasets containing socio-economic and climate information for relevant regions. This study has a broad impact on advancing knowledge regarding epidemic trends and prevention priorities in diverse salmonellosis outbreaks and guiding rational policy-making or predictive modeling to mitigate the infringement upon the right to life imposed by significant epidemics.

Microbiological hazards in infant and toddler food in China: A comprehensive study between 2004 and 2022.

Infant and toddler food (ITF), including powdered infant and follow-up formula (PIFF) and complementary food (CF), provides the majority of early-life nutrients for young children. As infants and toddlers are more vulnerable to foodborne diseases, the safety concern of ITF is the ultimate priority. However, nationwide surveillance for the presence of hazards, specifically microbiological hazards, in the Chinese ITF is partially known, posing a significant knowledge gap for risk ranking. Most importantly, the related regional surveys were largely published in Chinese, making the data unavailable for global sharing. To bridge these gaps, we screened 5,306 publications and conducted a comprehensive meta-analysis for microbiological hazards using 129 qualified studies. The four most reported microbiological hazards in ITF were Bacillus cereus (13.4 %), Cronobacter (4.8 %), Staphylococcus aureus (1.3 %), and Salmonella (1.1 %). B. cereus is a risk factor in ITF, specifically in PIFF, cereals, and ready-to-eat food. The prevalence of B. cereus was high in Northern and Southern China, while the prevalence of Cronobacter was high in Central China. Cronobacter is a microbiological hazard, specifically in PIFF, with a prevalence of 3.0 %. Interestingly, the prevalence dynamics of Cronobacter and B. cereus in ITF were rising and stable, respectively, whereas the prevalence of S. aureus and Salmonella decreased over time. Together, our analysis will promote the global sharing of these critical findings and may guide future policy making.

Fast and sensitive differential diagnosis of pseudorabies virus-infected versus pseudorabies virus-vaccinated swine using CRISPR-Cas12a.

IMPORTANCE: Pseudorabies virus (PRV) causes high mortality and miscarriage rates in the infected swine, and the eradication policy coupled with large-scale vaccination of live attenuated vaccines has been adopted globally against PRV. Differential diagnosis of the vaccinated and infected swine is highly demanded. Our multienzyme isothermal rapid amplification (MIRA)-Cas12a detection method described in this study can diagnose PRV with a superior sensitivity comparable to the quantitative PCR (qPCR) and a competitive detection speed (only half the time as qPCR needs). The portable feature and the simple procedure of MIRA-Cas12a make it easier to deploy for clinical diagnosis, even in resource-limited settings. The MIRA-Cas12a method would provide immediate and accurate diagnostic information for policymakers to respond promptly.

Beam-wise dose composition learning for head and neck cancer dose prediction in radiotherapy.

Automatic and accurate dose distribution prediction plays an important role in radiotherapy plan. Although previous methods can provide promising performance, most methods did not consider beam-shaped radiation of treatment delivery in clinical practice. This leads to inaccurate prediction, especially on beam paths. To solve this problem, we propose a beam-wise dose composition learning (BDCL) method for dose prediction in the context of head and neck (H&N) radiotherapy plan. Specifically, a global dose network is first utilized to predict coarse dose values in the whole-image space. Then, we propose to generate individual beam masks to decompose the coarse dose distribution into multiple field doses, called beam voters, which are further refined by a subsequent beam dose network and reassembled to form the final dose distribution. In particular, we design an overlap consistency module to keep the similarity of high-level features in overlapping regions between different beam voters. To make the predicted dose distribution more consistent with the real radiotherapy plan, we also propose a dose-volume histogram (DVH) calibration process to facilitate feature learning in some clinically concerned regions. We further apply an edge enhancement procedure to enhance the learning of the extracted feature from the dose falloff regions. Experimental results on a public H&N cancer dataset from the AAPM OpenKBP challenge show that our method achieves superior performance over other state-of-the-art approaches by significant margins. Source code is released at https://github.com/TL9792/BDCLDosePrediction.

Interphylum dissemination of NDM-5-positive plasmids in hospital wastewater from Fuzhou, China: a single-centre, culture-independent, plasmid transmission study.

BACKGROUND: The global spread of plasmid-borne carbapenem resistance is an ongoing public health challenge; however, the nature of such horizontal gene transfer events among complex bacterial communities remains poorly understood. We examined the in-situ transfer of the globally dominant New Delhi metallo-ß-lactamase (NDM)-5-positive IncX3 plasmid (denoted pX3_NDM-5) in hospital wastewater to simulate a real-world, One Health antimicrobial resistance context. METHODS: For this transmission study, we tagged pX3_NDM-5 with the green fluorescent protein gene, gfp, using a CRISPR-based method and transferred the plasmid to a donor Escherichia coli strain. Bacteria were extracted from a hospital wastewater treatment plant (Fujian Provincial Maternity and Children's Hospital, Fuzhou, China) as the bacterial recipient community. We mixed this recipient community with the E coli donor strain carrying the gfp-tagged plasmid, both with and without sodium hypochlorite (NaClO) as an environmental stressor, and conducted several culture-based and culture-independent conjugation assays. The conjugation events were observed microscopically and quantified by fluorescence-activated cell sorting. We analysed the taxonomic composition of the sorted transconjugal pool by 16S rRNA gene amplicon sequencing and assessed the stability of the plasmid in the isolated transconjugants and its ability to transfer back to E coli. FINDINGS: We show that the plasmid pX3_NDM-5 has a broad host range and can transfer across various bacterial phyla, including between Gram-negative and Gram-positive bacteria. Although environmental stress with NaClO did not affect the overall plasmid transfer frequency, it reduced the breadth of the transconjugant pool. The taxonomic composition of the transconjugal pool was distinct from that of the recipient communities, and environmental stress modulated the permissiveness of some operational taxonomic units towards the acquisition of pX3_NDM-5. Notably, pX3_NDM-5 transconjugants included the Gram-positive pathogen Enterococcus faecalis, and the plasmid could subsequently be reconjugated back to E coli. These findings suggest that E faecalis could act as a natural shuttle vector for the wide dissemination of pX3_NDM-5 plasmids. INTERPRETATION: Our culture-independent conjugation model simulates natural environmental conditions and challenges the established theory that Gram-negative and Gram-positive bacteria rarely exchange clinically important plasmids. The data show that plasmids disseminate more widely across genera and phyla than previously thought. These findings have substantial implications when considering the spread of antimicrobial resistance across One Health sectors. FUNDING: The Laboratory of Lingnan Modern Agriculture Project, the National Natural Science Foundation of China, the Natural Science Foundation of Fujian Province of China, and the Outstanding Young Research Talents Program of Fujian Agriculture and Forestry University.

Glutamate secretion by embryonic stem cells as an autocrine signal to promote proliferation.

Glutamate, the major excitatory neurotransmitter in the central nervous system, has also been found to play a role in embryonic stem (ES) cells. However, the exact mechanism and function of glutamatergic signaling in ES cells remain poorly understood. In this study, we identified a glutamatergic transmission circuit in ES cells that operates through an autocrine mechanism and regulates cell proliferation. We performed biological analyses to identify the key components involved in glutamate biosynthesis, packaging for secretion, reaction, and reuptake in ES cells, including glutaminase, vesicular glutamate transporter, glutamate N-methyl-D-aspartate (NMDA) receptor, and cell membrane excitatory amino-acid transporter (EAAT). We directly quantified the released glutamate signal using microdialysis-high performance liquid chromatography-tandem mass spectrometry (MD-HPLC-MS-MS). Pharmacological inhibition of endogenous glutamate release and the resulting tonic activation of NMDA receptors significantly affected ES cell proliferation, suggesting that ES cells establish a glutamatergic autocrine niche via releasing and responding to the transmitter for their own regulation.

Genome degradation promotes Salmonella pathoadaptation by remodeling fimbriae-mediated proinflammatory response.

Understanding changes in pathogen behavior (e.g. increased virulence, a shift in transmission channel) is critical for the public health management of emerging infectious diseases. Genome degradation via gene depletion or inactivation is recognized as a pathoadaptive feature of the pathogen evolving with the host. However, little is known about the exact role of genome degradation in affecting pathogenic behavior, and the underlying molecular detail has yet to be examined. Using large-scale global avian-restricted Salmonella genomes spanning more than a century, we projected the genetic diversity of Salmonella Pullorum (bvSP) by showing increasingly antimicrobial-resistant ST92 prevalent in Chinese flocks. The phylogenomic analysis identified three lineages in bvSP, with an enhancement of virulence in the two recently emerged lineages (L2/L3), as evidenced in chicken and embryo infection assays. Notably, the ancestor L1 lineage resembles the Salmonella serovars with higher metabolic flexibilities and more robust environmental tolerance, indicating stepwise evolutionary trajectories towards avian-restricted lineages. Pan-genome analysis pinpointed fimbrial degradation from a virulent lineage. The later engineered fim-deletion mutant, and all other five fimbrial systems, revealed behavior switching that restricted horizontal fecal-oral transmission but boosted virulence in chicks. By depleting fimbrial appendages, bvSP established persistent replication with less proinflammation in chick macrophages and adopted vertical transovarial transmission, accompanied by ever-increasing intensification in the poultry industry. Together, we uncovered a previously unseen paradigm for remodeling bacterial surface appendages that supplements virulence-enhanced evolution with increased vertical transmission.

Mobilome-driven partitions of the resistome in Salmonella.

IMPORTANCE: Antimicrobial resistance (AMR) has become a significant global challenge, with an estimated 10 million deaths annually by 2050. The emergence of AMR is mainly attributed to mobile genetic elements (MGEs or mobilomes), which accelerate wide dissemination among pathogens. The interaction between mobilomes and AMR genes (or resistomes) in Salmonella, a primary cause of diarrheal diseases that results in over 90 million cases annually, remains poorly understood. The available fragmented or incomplete genomes remain a significant limitation in investigating the relationship between AMR and MGEs. Here, we collected the most extensive closed Salmonella genomes (n = 1,817) from various sources across 58 countries. Notably, our results demonstrate that resistome transmission between Salmonella lineages follows a specific pattern of MGEs and is influenced by external drivers, including certain socioeconomic factors. Therefore, targeted interventions are urgently needed to mitigate the catastrophic consequences of Salmonella AMR.

An integrated nationwide genomics study reveals transmission modes of typhoid fever in China.

IMPORTANCE: Typhoid fever is a life-threatening disease caused by Salmonella enterica serovar Typhi, resulting in a significant disease burden across developing countries. Historically, China was very much close to the global epicenter of typhoid, but the role of typhoid transmission within China and among epicenter remains overlooked in previous investigations. By using newly produced genomics on a national scale, we clarify the complex local and global transmission history of such a notorious disease agent in China spanning the most recent five decades, which largely undermines the global public health network.

Glycopolypeptide hydrogels with adjustable enzyme-triggered degradation: A novel proteoglycans analogue to repair articular-cartilage defects.

Proteoglycans (PGs), also known as a viscous lubricant, is the main component of the cartilage extracellular matrix (ECM). The loss of PGs is accompanied by the chronic degeneration of cartilage tissue, which is an irreversible degeneration process that eventually develops into osteoarthritis (OA). Unfortunately, there is still no substitute for PGs in clinical treatments. Herein, we propose a new PGs analogue. The Glycopolypeptide hydrogels in the experimental groups with different concentrations were prepared by Schiff base reaction (Gel-1, Gel-2, Gel-3, Gel-4, Gel-5 and Gel-6). They have good biocompatibility and adjustable enzyme-triggered degradability. The hydrogels have a loose and porous structure suitable for the proliferation, adhesion, and migration of chondrocytes, good anti-swelling, and reduce the reactive oxygen species (ROS) in chondrocytes. In vitro experiments confirmed that the glycopolypeptide hydrogels significantly promoted ECM deposition and up-regulated the expression of cartilage-specific genes, such as type-II collagen, aggrecan, and glycosaminoglycans (sGAG). In vivo, the New Zealand rabbit knee articular cartilage defect model was established and the hydrogels were implanted to repair it, the results showed good cartilage regeneration potential. It is worth noting that the Gel-3 group, with a pore size of 122 â€‹± â€‹12 â€‹µm, was particularly prominent in the above experiments, and provides a theoretical reference for the design of cartilage-tissue regeneration materials in the future.

An Intelligent System to Sense Textual Cues for Location Assistance in Autonomous Vehicles.

The current technological world is growing rapidly and each aspect of life is being transformed toward automation for human comfort and reliability. With autonomous vehicle technology, the communication gap between the driver and the traditional vehicle is being reduced through multiple technologies and methods. In this regard, state-of-the-art methods have proposed several approaches for advanced driver assistance systems (ADAS) to meet the requirement of a level-5 autonomous vehicle. Consequently, this work explores the role of textual cues present in the outer environment for finding the desired locations and assisting the driver where to stop. Firstly, the driver inputs the keywords of the desired location to assist the proposed system. Secondly, the system will start sensing the textual cues present in the outer environment through natural language processing techniques. Thirdly, the system keeps matching the similar keywords input by the driver and the outer environment using similarity learning. Whenever the system finds a location having any similar keyword in the outer environment, the system informs the driver, slows down, and applies the brake to stop. The experimental results on four benchmark datasets show the efficiency and accuracy of the proposed system for finding the desired locations by sensing textual cues in autonomous vehicles.

Infant food production environments: A potential reservoir for vancomycin-resistant enterococci non-nosocomial infections.

Enterococcus has been considered one of the most important nosocomial pathogens for human infections, and the hospital environment is an important reservoir for vancomycin-resistant enterococci (VRE) that leads to antimicrobial therapeutic failure. However, infant foods and their production environments could pose risks for the immature population, while this question remains unaddressed. This study conducted an extensive and thorough Enterococcus isolation, VRE risk assessment of the Chinese infant food production chains and additional online-marketing infant foods, including powdered infant formula (PIF) and infant complementary food (ICF). To investigate the prevalence of Enterococcus along infant food chains and commodities, a total of 482 strains of Enterococcus, including E. faecium (n = 363), E. faecalis (n = 84), E. casseliflavus (n = 13), E. mundtii (n = 12), E. gallinarum (n = 4), E. hirae (n = 4), and E. durans (n = 2) were recovered from 459 samples collected from infant food production chains (71/254) and food commodities (67/205). A decreasing trend for Enterococcus detection rate was found in the PIF production chain (PIF-PC), particularly during the preparation of the PIF base powder (From 100 % in raw milk to 8.70 % in end products), while an increasing trend was observed in the ICF production chain (ICF-PC) mainly during the initial processing of farm crops and the further processing of the product (20 % at farm crops increasing to 76.92 % at end products). The result indicated that the PIF-PC process effectively reduced Enterococcus contamination, while the ICF-PC showed the opposite trend. Importantly, eleven VRE isolates were recovered from the infant food production chain, including seven E. casseliflavus isolates carrying vanC2/C3 and four E. gallinarum isolates carrying vanC1. Ten VRE isolates were from food production environments. Collectively, our study demonstrated that infant food production environments represent potential reservoirs for VRE non-nosocomial infections in vulnerable populations.

A Cross-Sectional Study of Companion Animal-Derived Multidrug-Resistant Escherichia coli in Hangzhou, China.

Antimicrobial resistance poses a challenge to global public health, and companion animals could serve as the reservoir for antimicrobial-resistant bacteria. However, the prevalence of antimicrobial-resistant bacteria, especially multidrug-resistant (MDR) bacteria, and the associated risk factors from companion animals are partially understood. Here, we aim to investigate the prevalence of MDR Escherichia coli, as an indicator bacterium, in pet cats and dogs in Hangzhou, China, and evaluate the factors affecting the prevalence of MDR E. coli. The proportion of pets carrying MDR E. coli was 35.77% (49/137), i.e., 40.96% (34/83) for dogs and 27.28% (15/54) for cats. Isolates resistant to trimethoprim-sulfamethoxazole (49.40% and 44.44%), amoxicillin-clavulanic acid (42.17% and 38.89%), and nalidixic acid (40.96% and 35.19%) were the most prevalent in dogs and cats. Interestingly, comparable prevalence of MDR E. coli was observed in pet dogs and cats regardless of the health condition and the history of antibiotic use. Genetic diversity analysis indicates a total of 86 sequencing types (23 clonal complexes), with ST12 being the most dominant. Further genomic investigation of a carbapenem-resistant E. coli ST410 isolate reveals abundant antimicrobial-resistance genes and a plasmid-borne carbapenemase gene (NDM-5) flanked by insertion sequences of IS91 and IS31, suggesting the plasmid and insertion sequences may be involved in carbapenem-resistance dissemination. These data show that companion animal-derived MDR bacteria could threaten public health, and further regulation and supervision of antimicrobial use in pet clinics should be established in China. IMPORTANCE MDR Escherichia coli are considered a global threat because of the decreasing options for antimicrobial therapy. Companion animals could be a reservoir of MDR E. coli, and the numbers of pets and households owning pets in China are booming. However, the prevalence and risk factors of MDR E. coli carriage in Chinese pets were rarely studied. Here, we investigated the prevalence of MDR E. coli in pets in Hangzhou, one of the leading cities with the most established pet market in China, and explored the factors that affected the prevalence. Our findings showed high prevalences of MDR E. coli in pet dogs and cats regardless of their health condition and the history of antibiotic use, suggesting their potential role of public health risk. A call-to-action for improved regulation of antimicrobial use in companion animal is needed in China.

Combined Medial and Lateral Approach Versus Paratricipital Approach in Open Reduction and Internal Fixation for Type C Distal Humerus Fracture: A Randomized Controlled Study.

OBJECTIVE: Olecranon osteotomy and paratricipital approaches were widely used in the treatment of type C distal humerus fracture but some disadvantages exist, so a combined medial and lateral approach was designed. The objective of this study was to investigate and compare the clinical outcomes of combined medial and lateral approach with the paratricipital approach in open reduction and internal fixation of type C distal humerus fractures. METHODS: From May 2018 to April 2020, 37 patients with type C distal humerus fracture who accepted open reduction and internal fixation in our hospital were enrolled in this study. All cases were randomly divided into two groups according to the surgical approach: combined medial and lateral approach group (19 cases), paratricipital approach group (18 cases). All of the patients received open reduction and double vertical plates fixation. The operation and follow-up indexes, including operation time, blood loss, incision length, triceps muscle strength, flexion-extension arc of elbow and forearm rotation arc, were recorded and compared. Caja score was used to assess the quality of fractures reduction. Mayo Elbow Performance Score (MEPS) was used to evaluate the elbow function in the follow-up. Complications such as incision infection, ulnar nerve injury, degenerative osteoarthritis, and heterotopic ossification were analyzed. RESULTS: The differences in age, gender, and AO classification of fractures between two groups were not statistically significant (p > 0.05). The sum of medial and lateral incision length of combined approach group was longer than the midline incision of paratricipital approach group (15.4 ± 0.8 vs. 14.6 ± 0.8, p < 0.05), but there was no significant difference in operation time (103.5 ± 10.2 vs. 106.0 ± 8.8, p > 0.05), blood loss (71.3 ± 24.5 vs. 72.8 ± 24.6, p > 0.05), and Caja score (16.05 ± 5.67 vs. 15.56 ± 5.66, p > 0.05). During the follow-up, the MEPS of combined approach group was higher than that of paratricipital approach group at 3 months postoperatively (80.5 ± 5.7 vs. 68.9 ± 8.1, p < 0.05), but there was no significant difference in MEPS at 6 months postoperatively (83.9 ± 6.6 vs. 79.7 ± 7.0, p > 0.05) and at the last follow-up (86.8 ± 7.1 vs. 86.9 ± 7.7, p > 0.05) between the two groups. There was no significant difference in triceps muscle strength (p > 0.05), flexion-extension arc (126.8 ± 5.3 vs. 128.9 ± 6.0, p > 0.05), and forearm rotation arc (163.2 ± 5.3 vs. 163.6 ± 4.8, p > 0.05) at the last follow-up. Although the incidence of complication of combined approach group (15.8%) was lower than that of paratricipital approach group (22.2%), the difference was not statistically significant (p > 0.05). CONCLUSIONS: The combined medial and lateral approach was an effective and safe way of open reduction and internal fixation for type C distal humerus fractures. Compared with the paratricipital approach, the combined medial and lateral approach could restore the elbow function more quickly postoperatively, and the long-term results were comparable.

Identification of nine mutant genes and establishment of three prediction models of organ tropism metastases of non-small cell lung cancer.

BACKGROUND: Most Non-small cell lung cancer (NSCLC) patients tend to have metastases at the initial diagnosis. However, limited knowledge has been established regarding which factors, are associated with its metastases. This study aims to identify more biomarkers associated with its organ tropism metastasis and to establish models for prediction of its metastatic organs. METHODS: We performed targeted next-generation sequencing (NGS) to detect genes related to lung cancer in 272 patients with primary advanced NSCLC from Northeast China. We adopted Fisher test, multivariate logistic regression analysis to identify metastasis-related gene mutations and to establish prediction models. RESULTS: Mutations of EGFR (p = 0.0003, OR = 2.554) (especially EGFR L858R [p = 0.02, OR = 2.009]), ATM (p = 0.008, OR = 11.032), and JAK2 (p = 0.009, OR = Inf) were positively and of TP53 exon4mut (p = 0.001, OR = 0.173) was negatively correlated with lung metastasis, and those of CSF1R (p = 0.01, OR = Inf), KIT (p = 0.03, OR = 4.746), MYC (p = 0.05, OR = 7.938), and ERBB2 (p = 0.02, OR = 2.666) were positively correlated with pleural dissemination; those of TP53 (p = 0.01, OR = 0.417) was negatively, while of SMAD4 (p = 0.03, OR = 4.957) was positively correlated with brain metastasis of NSCLC. Additionally, smoking history (p = 0.004, OR = 0.004) was negatively correlated with pleural dissemination of NSCLC. Furthermore, models for prediction of lung metastasis (AUC = 0.706), pleural dissemination (AUC = 0.651), and brane metastasis (AUC = 0.629) were established. CONCLUSION: Taken together, this study revealed nine mutant genes and smoking history associated with organ tropism metastases of NSCLC and provided three models for the prediction of metastatic organs. This study enables us to predict the organs to which non-small cell lung cancer metastasizes before it does develop.

Phage controlling method against novel freshwater-derived Vibrio parahaemolyticus in ready-to-eat crayfish (Procambarus clarkii).

Vibrio parahaemolyticus is a halophilic foodborne pathogen majorly isolated from seafood, threatening public health worldwide. However, our recent study reported the presence of this bacterium in freshwater crayfish, which were rarely identified and investigated. Its pathogenicity and genomic features remain unclear, and the controlling method to inhibit this bacterium in ready-to-eat (RTE) crayfish is not developed. Compared with a clinical strain (ATCC17802), the representative strain (LVP1) from freshwater crayfish showed higher pathogenicity in a zebrafish model, indicating its hypervirulence and foodborne infection risk. Unlike most clinical V. parahaemolyticus isolates that carried tdh and (or) trh, two classic virulence factor genes associated with clinical infections, the hypervirulent LVP1 lacked these two genes, indicating it is a novel strain and other unknown virulence factors play key roles in its pathogenicity. Genomic and phylogenetic analyses demonstrated this strain is V. parahaemolyticus, while it is phylogenetically distant from other global isolates. Therefore, LVP1 is considered a novel V. parahaemolyticus strain from freshwater crayfish, being hypervirulent, and lacking virulence marker genes. The antimicrobial resistant genes drfA6 and qnrV1 were unique in LVP1 and absent in other reference V. parahaemolyticus strains. Antimicrobial susceptibility testing confirms it as multidrug resistance, with resistance to ampicillin, amoxicillin/clavulanate, trimethoprim, and colistin. To control this novel and multidrug-resistant V. parahaemolyticus strain in food production chains, we developed a phage cocktail and applied it to the surface of RTE crayfish meat, resulting in a significant decrease in the bacterial load by 2.36 log10 CFU/mL. These data highlight freshwater food products pose threats to public health through 'farm-to-fork' transmission of hypervirulent V. parahaemolyticus and reveal the phage cocktail as a promising method to attenuate this bacterium in RTE food, emphasizing the necessity to prevent food contamination caused by this bacterium from freshwater products.

Hydrogen-Induced Dislocation Nucleation and Plastic Deformation of 〈001〉 and 〈11¯0〉 Grain Boundaries in Nickel.

The grain boundary (GB) plays a crucial role in dominating hydrogen-induced plastic deformation and intergranular failure in polycrystal metals. In the present study, molecular dynamics simulations were employed to study the effects of hydrogen segregation on dislocation plasticity of a series of symmetrical tilt grain boundaries (STGBs) with various hydrogen concentrations. Our study shows that hydrogen both enhances and reduces dislocation nucleation events from STGBs, depending on different GB structures. Specifically, for ⟨001⟩ STGBs, hydrogen does not affect the mode of heterogeneous dislocation nucleation (HDN), but facilitates nucleation events as a consequence of hydrogen disordering the GB structure. Conversely, hydrogen retards dislocation nucleation due to the fact that hydrogen segregation disrupts the transformation of boundary structure such as Σ9 (2 2 1¯) ⟨11¯0⟩ STGB. These results are helpful for deepening our understanding of GB-mediated hydrogen embrittlement (HE) mechanisms.

A nontyphoidal Salmonella serovar domestication accompanying enhanced niche adaptation.

Invasive nontyphoidal Salmonella (iNTS) causes extraintestinal infections with ~15% case fatality in many countries. However, the mechanism by which iNTS emerged in China remains unaddressed. We conducted clinical investigations of iNTS infection with recurrent treatment failure, caused by underreported Salmonella enterica serovar Livingstone (SL). Genomic epidemiology demonstrated five clades in the SL population and suggested that the international animal feed trade was a likely vehicle for their introduction into China, as evidenced by multiple independent transmission incidents. Importantly, isolates from Clade-5-I-a/b, predominant in China, showed an invasive nature in mice, chicken and zebrafish infection models. The antimicrobial susceptibility testing revealed most isolates (> 96%) in China are multidrug-resistant (MDR). Overall, we offer exploiting genomics in uncovering international transmission led by the animal feed trade and highlight an emerging hypervirulent clade with increased resistance to frontline antibiotics.