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Abstract Objective Immune-mediated necrotising myopathy (IMNM) is a subset of idiopathic inflammatory myopathies (IIM) characterized by significantly elevated creatine kinase level, muscle weakness and predominant muscle fibre necrosis in muscle biopsy. This study aimed to investigate the clinical and pathological characteristics of patients with IMNM in a single-centre muscle biopsy cohort. Methods A total of 860 patients who had muscle biopsy reports in our centre from May 2008 to December 2017 were enrolled in this study. IMNM was diagnosed according to the 2018 European Neuromuscular Centre (ENMC) clinicopathological diagnostic criteria for IMNM. Results The muscle biopsy cohort consisted of 531 patients with IIM (61.7%), 253 patients with non-IIM (29.4%), and 76 undiagnosed patients (8.8%). IIM cases were classified as IMNM (68[7.9%]), dermatomyositis (346[40.2%]), anti-synthetase syndrome (82[9.5%]), polymyositis (32[3.7%]), and sporadic inclusion body myositis (3[0.3%]). Limb girdle muscular dystrophy (LGMD) 2B and lipid storage myopathy (LSM) are the two most common non-IIM disorders in our muscle biopsy cohort. IMNM patients had a higher onset age (41.57 ± 14.45 vs 21.66 ± 7.86 and 24.56 ± 10.78, p

Let $ f:\, X\to Y $ be a semistable non-isotrivial family of $ n $-folds over a smooth projective curve with discriminant locus $ S \subseteq Y $ and with general fiber $ F $ of general type. We show the strict Arakelov inequality $ {\deg f_*\omega_{X/Y}^\nu \over {{{\rm{rank\,}}}} f_*\omega_{X/Y}^\nu} < {n\nu\over 2}\cdot\deg\Omega^1_Y(\log S), $ for all $ \nu\in \mathbb N $ such that the $ \nu $-th pluricanonical linear system $ |\omega^\nu_F| $ is birational. This answers a question asked by Möller, Viehweg and the third named author [1].

Abstract Background Occult breast cancer (OBC) is a special type of breast cancer. Because of its rarity, clinicopathological information is still insufficient, causing a controversial condition about its treatment recommendation. Thus, we aimed to clarify major clinicopathological information, treatment strategies and prognosis of OBC based on a large population. Methods We retrospectively collected adult female OBC population from Surveillance, Epidemiology, and End Results database. We divided the whole cohort into two groups based on surgical treatment in-breast. Descriptive analysis of 18 clinicopathological variables was conducted. Survival analysis was performed based on different clinicopathological factors. Univariate and multivariate Cox regression analysis was performed to identify potential independent predictor for prognosis of OBC. Results 1189 OBC patients were in final analysis and most of them were diagnosed as an early-stage carcinoma. Patients received breast-conserving treatment (BCT) was nearly two times of ones received mastectomy. Patients receiving radiotherapy in BCT group were significantly more than patients receiving radiotherapy in mastectomy group (61.76 vs. 50.9%, P

The influence of structural parameters on the thermal resistance of electrical heat sinks with a circular heating area is analyzed using a numerical model experimentally verified. The correlation of the dimensionless thermal resistance regarding to working parameters and other geometric parameters is obtained. The correlation not only can reveal various kinds of the trends of thermal resistance changes with the parameters but also can directly predict the thermal resistance. The results provide a theoretical basis for designing this type of heat sink.

Summary: Background: Synergistic antitumor effects of immunotherapy and chemotherapy have been demonstrated in several solid tumors. However, this combination strategy has not been addressed in gestational trophoblastic neoplasia (GTN) cases. We therefore compared the safety and therapeutic effect of anti-programmed cell death 1 (PD-1) therapy combined with chemotherapy versus anti-PD-1 monotherapy among high-risk chemorefractory or relapsed GTN patients. Methods: This retrospective cohort study was conducted at three teaching hospitals in China. Chemorefractory or relapsed GTN cases receiving anti-PD-1 therapy combined with chemotherapy or anti-PD-1 monotherapy were selected from each center between August 2018 and March 2022. Study endpoints included objective response rate (ORR), treatment duration, overall survival (OS) and progression-free survival (PFS). The nature, prevalence and severity of treatment-related adverse events (TRAEs) were evaluated. Findings: This work enrolled 66 cases. Thirty-five and 31 patients received anti-PD-1 therapy alone and combined with chemotherapy, respectively. The combined treatment dramatically increased the objective response rate from 62.9% (22/35) to 96.8% (30/31) (p

Phosphate solubilizing microorganisms (PSMs) are known as bacteria or fungi that make insoluble phosphorus in soil available to plants. To date, as beneficial microbes, studies on PSMs indicated they have potential applications in agriculture, environmental engineering, bioremediation, and biotechnology. Currently high cost and competition from local microbe are the most important factors hindering PSMs commercialization and application as for instance biofertilizer, soil conditioner or remediation agent, etc. There are several technical strategies can be engaged to approach the solutions of these issues, for instance mass production, advance soil preparation, genetic engineering, etc. On the other hand, further studies are needed to improve the efficiency and effectiveness of PSMs in solubilizing phosphates, promoting plant growth, soil remediation preferably. Hopefully, PSMs are going to be developed into ecofriendly tools for sustainable agriculture, environment protection and management in the future.

IntroductionGenome-based analysis is crucial in monitoring antibiotic-resistant bacteria (ARB)and antibiotic-resistance genes (ARGs). Short-read sequencing is typically used to obtain incomplete draft genomes, while long-read sequencing can obtain genomes of multidrug resistance (MDR) plasmids and track the transmission of plasmid-borne antimicrobial resistance genes in bacteria. However, long-read sequencing suffers from low-accuracy base calling, and short-read sequencing is often required to improve genome accuracy. This increases costs and turnaround time.MethodsIn this study, a novel ONT sequencing method is described, which uses the latest ONT chemistry with improved accuracy to assemble genomes of MDR strains and plasmids from long-read sequencing data only. Three strains of Salmonella carrying MDR plasmids were sequenced using the ONT SQK-LSK114 kit with flow cell R10.4.1, and de novo genome assembly was performed with average read accuracy (Q > 10) of 98.9%.Results and DiscussionFor a 5-Mb-long bacterial genome, finished genome sequences with accuracy of >99.99% could be obtained at 75× sequencing coverage depth using Flye and Medaka software. Thus, this new ONT method greatly improves base-calling accuracy, allowing for the de novo assembly of high-quality finished bacterial or plasmid genomes without the need for short-read sequencing. This saves both money and time and supports the application of ONT data in critical genome-based epidemiological analyses. The novel ONT approach described in this study can take the place of traditional combination genome assembly based on short- and long-read sequencing, enabling pangenomic analyses based on high-quality complete bacterial and plasmid genomes to monitor the spread of antibiotic-resistant bacteria and antibiotic resistance genes.

Pneumatosis cystoides intestinalis (PCI) in adult dermatomyositis (DM) is rarely described. This report aimed to describe the clinical features and prognosis of PCI in six adult patients with DM (four with anti-MDA5 antibodies, one with anti-SAE antibodies, and one with anti-TIF-1γ antibodies). Except for one patient with transient abdominal pain, the remaining five patients were asymptomatic. PCI occurred in the ascending colon in all patients, of whom five had free gas in the abdominal cavity. No patients received excessive treatment, and PCI disappeared in four patients during the follow-up. Additionally, we reviewed previous studies on this complication.

Introduction To investigate the clinical, radiographic and pathological features of interstitial lung disease (ILD) in patients with anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis (anti-MDA5+DM).Methods We retrospectively analysed the medical records of patients with anti-MDA5+DM who had undergone radiological examination, and lung histopathology was performed on 17 of them.Results This study examined 329 patients with anti-MDA5+DM, of whom 308 (93.6%) were diagnosed with ILD and 177 (53.8%) exhibited rapidly progressive ILD (RPILD). The most common radiographic patterns were organising pneumonia (OP) (43.2%), non-specific interstitial pneumonia (NSIP) (26.4%) and NSIP+OP (18.5%). Histological analysis showed NSIP (41.2%) and NSIP+OP (47.1%) to be the predominant patterns. However, in the 17 patients who underwent lung histopathology, the coincidence rate between radiological and histopathological diagnoses was only 11.8%. Compared with patients without RPILD, those with RPILD showed a higher prevalence of NSIP+OP (26.6% vs 10.7%, p=0.001) and a lower prevalence of NSIP pattern (21.5% vs 37.4%, p=0.002) on high-resolution CT. Furthermore, patients with radiographic patterns of NSIP+OP or diffuse alveolar damage (DAD) had more risk factors for poor prognosis, with 12-month mortality rates of 45.9% and 100%, respectively.Conclusions RPILD was commonly observed in patients with anti-MDA5+DM. OP was identified as the predominant radiographic pattern, which corresponded to a histopathological pattern of NSIP or NSIP+OP. Notably, patients exhibiting radiographic patterns of NSIP+OP or DAD were shown to have a poor prognosis.

A 58-year-old male was admitted to the liver surgery ward of Peking Union Medical College Hospital as the result of recurrent cholangitis in the past six months. Preoperative abdominal CT and gastrointestinal radiography showed duodenal dilatation and reconstruction of gastrointestinal tract, which might be related to the laparotomy and hemostasis performed due to traffic accident 30 years ago. The operative method of that surgery might be the reason for the patient's choledocholithiasis and duodenal dilatation.

The heat transfer ability of ventilated passage of the disc brake has important effect on heat dissipation rate of the disc brake. The disc brake using uniform diameter circular pin fins to form ventilated passages has been widely used, but there is less reported heat transfer performance data of this type of ventilated passage. This paper investigated the heat transfer characteristics of the ventilated passage which is 10 times smaller than the real ventilated passage. The effects of the geometric parameters of the passage on its heat transfer ability are studied. The results show that the diameter and the number of the pin fin have stronger effect than the height of the pin fin has on the heat transfer. The results show great difference between the results predicted by the available correlation for ventilated passage formed by straight vane at small or large Reynolds number region. The reasons that cause the difference between the present results and other reported results are discussed. A correlation of Nusselt number vs. Reynolds number, the diameter, the number and the height of the pin fin is provided.

Abstract Efficiently improving the moisture stability of β‐Li3PS4 materials could significantly reduce production costs and eventually enable the mass application. Nanoporous multiphase β‐Li3PS4 materials prepared via solvent‐assistant routes usually contain solvent or solvent decomposition segments associated with the amorphous Li3PS4 phase in their structures. Herein, the solvent ethyl propionate (EP) remains in the β‐Li3PS4 even after 220 h of annealing at 220°C. The possibility of tuning the moisture stability of β‐Li3PS4 by adjusting the content of the solvent is investigated by environmental scanning electron microscopy (ESEM) combined with other structural analysis techniques. The results demonstrated that the hydrogen‐containing amorphous Li3PS4 not only stabilizes the β‐phase at room temperature but also improves the moisture stability of the material. Although the rapid hydrolysis occurs on the surface of solvent‐containing β‐Li3PS4 materials under ambient conditions within 10 s, with 4 wt% EP content, the material can be exposed to 1.6% relative humidity (R.H.) for at least 8 h without any structural or microstructural change. Even with the lower amount of EP (1.2 wt%) in the Li3PS4 structure, the material can withstand 1% R.H. for more than 8 h, which allows the material to be manufactured in a dry room. Our observation proposes a simple method to slightly modify the moisture stability of β‐Li3PS4 to match the different manufacturing conditions.

Curcumin, the primary bioactive substance in turmeric, exhibits potential therapeutic effects on ulcerative colitis. However, its mechanism for regulating necroptosis in colitis has not been fully elucidated. In this study, the effect of curcumin on experimental colitis-induced necroptosis of intestinal epithelial cells was investigated, and its molecular mechanism was further explored. We found that curcumin blocked necroptosis in a dose-dependent manner by inhibiting the phosphorylation of RIP3 and MLKL instead of RIP1 in HT-29 cells. Co-Immunoprecipitation assay showed that curcumin weakened the interaction between RIP1 and RIP3, possibly due to the direct binding of curcumin to RIP3 as suggested by drug affinity responsive target stability analysis. In a classical in vivo model of TNF-α and pan-caspase inhibitor-induced necroptosis in C57BL/6 mice, curcumin potently inhibited systemic inflammatory responses initiated by the necroptosis signaling pathway. Then, using a dextran sodium sulfate-induced colitis model in C57BL/6 mice, we found that curcumin inhibited the expression of p-RIP3 in the intestinal epithelium, reduced intestinal epithelial cells loss, improved the function of the intestinal tight junction barrier, and reduced local intestinal inflammation. Collectively, our findings suggest that curcumin is a potent targeted RIP3 inhibitor with anti-necroptotic and anti-inflammatory effects, maintains intestinal barrier function, and effectively alleviates colitis injury.

Liver cancer is the third greatest cause of cancer-related mortality, which of the major pathological type is hepatocellular carcinoma (HCC) accounting for more than 90%. HCC is characterized by high mortality and is predisposed to metastasis and relapse, leading to a low five-year survival rate and poor clinical prognosis. Numerous crosstalk among tumor parenchymal cells, anti-tumor cells, stroma cells, and immunosuppressive cells contributes to the immunosuppressive tumor microenvironment (TME), in which the function and frequency of anti-tumor cells are reduced with that of associated pro-tumor cells increasing, accordingly resulting in tumor malignant progression. Indeed, sorting out and understanding the signaling pathways and molecular mechanisms of cellular crosstalk in TME is crucial to discover more key targets and specific biomarkers, so that develop more efficient methods for early diagnosis and individualized treatment of liver cancer. This piece of writing offers insight into the recent advances in HCC-TME and reviews various mechanisms that promote HCC malignant progression from the perspective of mutual crosstalk among different types of cells in TME, aiming to assist in identifying the possible research directions and methods in the future for discovering new targets that could prevent HCC malignant progression.

Background: In recent years, liquid biopsy has shown great potential for improving cancer diagnosis and treatment. This study aimed to explore the trends and prospects in liquid biopsy for cancer from a bibliometric perspective.Methods: Reviews and articles on liquid biopsy and cancer were collected from the Web of Science Core Collection (WoSCC). Key bibliometric characteristics were analyzed using CiteSpace. Co-occurrence analysis of keywords and co-citation analysis of references was performed.Results: A total of 6331 publications from 11 years of scientific research were retrieved. Ninety-five countries and 7004 institutions in liquid biopsy and cancer contributed. The United States (US) and China published the most articles. The institution with the most published articles was the University of Texas MD Anderson Cancer Center. The most published journals were Cancer and Frontiers in Oncology. “Bettegowda (2014)'' was the most cited reference with the highest burst strength in the last decade. Cluster analysis revealed that the recent hot topics were “circulating tumor cells,” “cancer,” and “exosomes.''Conclusions: This bibliometric analysis maps the basic knowledge structure of the field of liquid biopsy for cancer. The field is entering a phase of rapid development. The hot spots identified in this study deserve further investigation.

The early embryo maintains its structure in the face of large mechanical stresses during morphogenesis. Here they show that ASPP2 acts to preserve epithelial integrity in regions of high apical tension during early development.

This paper develops a multisensor data fusion-based deep learning algorithm to locate and classify faults in a leader-following multiagent system. First, sequences of one-dimensional data collected from multiple sensors of followers are fused into a two-dimensional image. Then, the image is employed to train a convolution neural network with a batch normalisation layer. The trained network can locate and classify three typical fault types: the actuator limitation fault, the sensor failure and the communication failure. Moreover, faults can exist in both leaders and followers, and the faults in leaders can be identified through data from followers, indicating that the developed deep learning fault diagnosis is distributed. The effectiveness of the deep learning-based fault diagnosis algorithm is demonstrated via Quanser Servo 2 rotating inverted pendulums with a leader-follower protocol. From the experimental results, the fault classification accuracy can reach 98.9%.

Abstract Objectives The purpose was to clarify the characteristics of interstitial lung disease (ILD) in immune-mediated necrotizing myopathy (IMNM) patients with anti-signal recognition particle (SRP) antibodies. Methods Medical records of IMNM patients with anti-SRP antibodies were reviewed retrospectively. Results A total of 60 patients were identified. Twenty-seven (45.0%) patients were diagnosed with ILD based on lung imaging: nonspecific interstitial pneumonia (NSIP) in 17 patients (63.0%) and organizing pneumonia in 9 patients (33.3%). Reticulation pattern was identified in 17 patients (63.0%) whereas 10 cases (37.0%) showed ground glass opacity and patchy shadows by high-resolution computed tomography (HRCT). Pulmonary function tests (PFTs) were available in 18 patients, 6 (33.3%) and 10 (55.6%) patients were included in the mild and moderate group, respectively. The average age at the time of ILD onset was significantly older than those without ILD (48.6 ± 14.4 years vs. 41.2 ± 15.4 years, p

Abstract Background The development of an influenza vaccine for poultry that provides broadly protective immunity against influenza H5Nx viruses is a challenging goal. Results Lactococcus lactis (L. lactis)/pNZ8149-HA1-M2 expressing hemagglutinin-1 (HA1) of A/chicken/Vietnam/NCVD-15A59/2015 (H5N6) and the conserved M2 gene of A/Vietnam/1203/2004 (H5N1) was generated. L. lactis/pNZ8149-HA1-M2 could induce significant humoral, mucosal and cell-mediated immune responses, as well as neutralization antibodies. Importantly, L. lactis/pNZ8149-HA1-M2 could prevent disease symptoms without significant weight loss and confer protective immunity in a chicken model against lethal challenge with divergent influenza H5Nx viruses, including H5N6 and H5N1. Conclusions L. lactis/pNZ8149-HA1-M2 can serve as a promising vaccine candidate in poultry industry for providing protection against H5Nx virus infection in the field application.

Shigella is one of the main food-borne pathogens, and its low infectious dose and serious hazard have attracted people's attention. Therefore, it is essential to develop rapid, sensitive and efficient methods for the detection of Shigella and to ensure food quality and safety. Methods for detecting Shigella can be divided into three categories: traditional culture methods, immunological methods and molecular biology methods. Many studies have made various improvements in order to make the detection technology more practical in sample detection. This article reviews recent methods for the detection of Shigella, including improved traditional methods, immunological methods, molecular biology methods, as well as new and emerging detection methods. The application scope and progress of these methods are highlighted to provide a reference for the selection of detection methods for Shigella.

Abstract Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease in the central nervous system (CNS). The NLRP3 inflammasome is considered an important regulator of immunity and inflammation, both of which play a critical role in MS. However, the underlying mechanism of NLRP3 inflammasome activation is not fully understood. Here we identified that the TRPV1 (transient receptor potential vanilloid type 1) channel in microglia, as a Ca2+ influx-regulating channel, played an important role in NLRP3 inflammasome activation. Deletion or pharmacological blockade of TRPV1 inhibited NLRP3 inflammasome activation in microglia in vitro. Further research revealed that TRPV1 channel regulated ATP-induced NLRP3 inflammasome activation through mediating Ca2+ influx and phosphorylation of phosphatase PP2A in microglia. In addition, TRPV1 deletion could alleviate mice experimental autoimmune encephalomyelitis (EAE) and reduce neuroinflammation by inhibiting NLRP3 inflammasome activation. These data suggested that the TRPV1 channel in microglia can regulate NLRP3 inflammasome activation and consequently mediate neuroinflammation. Meanwhile, our study indicated that TRPV1–Ca2+–PP2A pathway may be a novel regulator of NLRP3 inflammasome activation, pointing to TRPV1 as a potential target for CNS inflammatory diseases.

Due to the diversity and variability of Chinese syntax and semantics, accurately identifying and distinguishing individual emotions from online texts is challenging. To overcome this limitation, we incorporate a new source of individual sentiment, emojis, which contain thousands of graphic symbols and are increasingly being used for expressing emotion in online conversations. We examined popular sentiment analysis algorithms, including rule-based and classification algorithms, to evaluate the impact of supplementing emojis as additional features to improve the algorithm performance. Emojis were also translated into corresponding sentiment words when constructing features for comparison with those directly generated from emoji label words. In addition, considering different functions of emojis in texts, we classified all posts in the dataset by their emoji usage and examined the changes in algorithm performance. We found that emojis are effective as expanding features for improving the accuracy of sentiment analysis algorithms, and the algorithm performance can be further increased by taking different emoji usages into consideration. In this study, we developed an improved emoji-embedding model based on Bi-LSTM (namely, CEmo-LSTM), which achieves the highest accuracy (around 0.95) when analyzing online Chinese texts. We applied the CEmo-LSTM algorithm to a large dataset collected from Weibo from December 1, 2019 to March 20, 2020 to understand the sentiment evolution of online users during the COVID-19 pandemic. We found that the pandemic remarkably impacted individual sentiments and caused more passive emotions (e.g., horror and sadness). Our novel emoji-embedding algorithm creatively combined emojis as well as emoji usage with the sentiment analysis model and can handle emotion mining tasks more effectively and efficiently.

Sustainability and environmental consciousness directed attention toward research and innovation in the field of natural fiber composites. Baobab (Adansonia digitata L.) is tropical tree of the silk-cotton family that is native to Africa. The aim of this study is to pore over the use of baobab bast fibers as potential reinforcement in polymer composites. The baobab bast fibers were extracted from the bark of baobab tree in Sudan. Fibers were investigated by chemical analysis, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and single fiber tensile test. Further, the density and relative humidity of fibers were determined.The cellulose, hemicellulose, lignin, ash, and moisture contents present in the fiber are 60.70%, 21.98%, 5.91%, 5.32%, 13%, respectively. The fiber has a density of 1.1041 g/cm3. FTIR spectra for cellulose and nanocellulose confirms absorption bands characteristic of pure celluloses at 3330, 2919, 1640, 1028. Scanning electron micrographs showed roughening of the fiber surface and crack-like lines indicate fiber clusters being held together. The baobab fiber possessed a crystallinity index of 48.01% with thermal stability up to 250°C. The results revealed that baobab fiber can be utilized as reinforcement in polymer composites.

Summary: At the moment of union in fertilization, sperm and oocyte are transcriptionally silent. The ensuing onset of embryonic transcription (embryonic genome activation [EGA]) is critical for development, yet its timing and profile remain elusive in any vertebrate species. We here dissect transcription during EGA by high-resolution single-cell RNA sequencing of precisely synchronized mouse one-cell embryos. This reveals a program of embryonic gene expression (immediate EGA [iEGA]) initiating within 4 h of fertilization. Expression during iEGA produces canonically spliced transcripts, occurs substantially from the maternal genome, and is mostly downregulated at the two-cell stage. Transcribed genes predict regulation by transcription factors (TFs) associated with cancer, including c-Myc. Blocking c-Myc or other predicted regulatory TF activities disrupts iEGA and induces acute developmental arrest. These findings illuminate intracellular mechanisms that regulate the onset of mammalian development and hold promise for the study of cancer.

ABSTRACT Candida albicans remains the most common species causing invasive candidiasis. In this study, we present the population structure of 551 global C. albicans strains. Of these, the antifungal susceptibilities of 370 strains were tested. Specifically, 66.6% of the azole-nonsusceptible (NS)/non-wild-type (NWT) strains that were tested belonged to Clade 1. A phylogenetic analysis, a principal components analysis, the population structure, and a loss of heterozygosity events revealed two nested subclades in Clade 1, namely, Clade 1-R and Clade 1-R-α, that exhibited higher azole-NS/NWT rates (75.0% and 100%, respectively). In contrast, 6.4% (21/326) of the non-Clade 1-R isolates were NS/NWT to at least 1 of 4 azoles. Notably, all of the Clade 1-R-α isolates were pan-azole-NS/NWT that carried unique A114S and Y257H double substitutions in Erg11p and had the overexpression of ABC-type efflux pumps introduced by the substitution A736V in transcript factor Tac1p. It is worth noting that the Clade 1-R and Clade 1-R-α isolates were from different cities that are distributed over a large geographic span. Our study demonstrated the presence of specific phylogenetic subclades that are associated with antifungal resistance among C. albicans Clade 1, which calls for public attention on the monitoring of the future spread of these clones. IMPORTANCE Invasive candidiasis is the most common human fungal disease among hospitalized patients, and Candida albicans is the predominant pathogen. Considering the large number of infected cases and the limited alternative therapies, the azole-resistance of C. albicans brings a huge clinical threat. Here, our study suggested that antifungal resistance in C. albicans could also be associated with phylogenetic lineages. Specifically, it was revealed that more than half of the azole-resistant C. albicans strains belonged to the same clade. Furthermore, two nested subclades of the clade exhibited extremely high azole-resistance. It is worth noting that the isolates of two subclades were from different cities that are distributed over a large geographic span in China. This indicates that the azole-resistant C. albicans subclades may develop into serious public health concerns.

Nowadays, adolescents would like to share their daily lives via social media platforms, which presents an excellent opportunity for us to leverage these data to develop techniques to measure their mental health status, such as depression. Previous researches focus on the more accurate detection of depression through statistical learning and ignore psychological understanding of depression. However, psychologists have given lots of theoretical evidence for depression. Such as according to cognitive psychology research, cognitive distortions will result in depression. Thus, in this study, we propose a new task, explainable depression detection, to not only automatically detect depression but also try to give clues to depression based on cognitive distortion theory. For this purpose, we construct a multi-task learning model based on a pre-trained model to detect depression and identify cognitive distortion. And we use many analytical means including word clouds for data analysis to draw our conclusion. Previous social media users' depression corpus and our cognitive distortion corpus are utilized for analysis and experiment. Our experimental results outperform the baseline results and interesting conclusions about adolescent depression are drawn.

Some serovars of Salmonella are not or rare found to cause salmonellosis in human. In our clinic-based surveillance, three rare Salmonella 4,5,12:a:- strains were recovered from three patients with diarrhea. To explore their genetic and epidemiological characteristics and pathogenesis, we conducted whole-genome sequencing, in vitro invasion assays in mammalian cells, and in vivo virulence assays in an animal model. The three isolates had indistinguishable molecular patterns and similar genome sequences, and clustered together with an isolate from edible fish traded among countries. The isolates had biochemical reactions identical with those of Salmonella subspecies enterica but belonged to subspecies salamae according to genome phylogeny, revealing a new serovar, S. enterica subsp. II serovar 4,5,12:a:-. The strains contained multiple virulence genes, elicited temporary bacteremia and enteritidis and caused cell damage in the mouse liver and cecum. This study provides evidence that this new Salmonella salamae serovar can infect humans and cause clusters of cases, and whole-genome sequencing detection and surveillance of Salmonella can help to accurately define Salmonella classification and clonality, improve diagnosis, facilitate outbreak detection and aid in the source tracing of salmonellosis epidemics.

To improve the mechanical compatibility and biocompatibility of porous scaffolds for dental application, functionally graded porous titanium scaffolds with average porosity of 20–80 % were designed and fabricated by selective laser melting. Finite element modeling in the oral environment showed that the maximum von-Mises strains of cortical and cancellous bone around graded scaffolds with 20–50 % porosities were in the range of 100–3000 με and 1000–3000 με, respectively, which is beneficial for bone regeneration. Additionally, the graded scaffolds exhibited higher compressive yield strength (206.1–477.5 MPa) yet suitable elastic modulus (8.5–20.7 GPa) compared with human cortical bone. Permeability of graded scaffolds increased with increasing porosity that all fall in the range of the permeability for human bone. Corrosion rate of graded scaffolds with 20–40 % porosity satisfied the corrosion resistance for metallic implants (2.5 × 10−4/mm/yr). Moreover, the graded scaffolds with 20–40 % porosity exhibited 0-I grade toxic effects on mouse embryonic osteoblast precursor cell proliferation in vitro. Taken together, the graded scaffold with 30 % porosity meets all requirements as a promising dental implant. In addition, this study provided a rational approach for screening the best geometrical design of the implants in dentistry.

BackgroundDespite providing clinical benefit, immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs) in a number of patients. This study explored the development pattern in irAEs research from a bibliometric perspective.MethodsWe obtained articles and reviews related to irAEs from the Web of Science Core Collection (WoSCC) (retrieved on September 13, 2022). Using the R package “Bibliometrix”, the main bibliometric features were calculated, and a three-filed plot was generated to show the relationship between authors, institutions, and topics. VOSviewer was used for co-authorship and keyword co-occurrence analysis and visualization. CiteSpace was used to detect burst references and keywords.ResultsA total of 3995 publications on irAEs were included. The United States (US), Japan, and China had the highest publications. The Journal for ImmunoTherapy of Cancer had the highest number of publications. In addition to “immune-related adverse events”, “immune checkpoint inhibitors”, “immunotherapy”, and “nivolumab” were the most frequently used keywords.ConclusionsA bibliometric analysis of 17 years of irAEs research was conducted to map a basic knowledge structure including countries, institutions, authors, journals, and publications. The findings provided a comprehensive perspective on the broad future of this research area.

Maize with a high kernel protein content (PC) is desirable for human food and livestock fodder. However, improvements in its PC have been hampered by a lack of desirable molecular markers. To identify quantitative trait loci (QTL) and candidate genes for kernel PC, we employed a genotyping-by-sequencing strategy to construct a high-resolution linkage map with 6,433 bin markers for 275 recombinant inbred lines (RILs) derived from a high-PC female Ji846 and low-PC male Ye3189. The total genetic distance covered by the linkage map was 2180.93 cM, and the average distance between adjacent markers was 0.32 cM, with a physical distance of approximately 0.37 Mb. Using this linkage map, 11 QTLs affecting kernel PC were identified, including qPC7 and qPC2-2, which were identified in at least two environments. For the qPC2-2 locus, a marker named IndelPC2-2 was developed with closely linked polymorphisms in both parents, and when tested in 30 high and 30 low PC inbred lines, it showed significant differences (P = 1.9E-03). To identify the candidate genes for this locus, transcriptome sequencing data and PC best linear unbiased estimates (BLUE) for 348 inbred lines were combined, and the expression levels of the four genes were correlated with PC. Among the four genes, Zm00001d002625, which encodes an S-adenosyl-L-methionine-dependent methyltransferase superfamily protein, showed significantly different expression levels between two RIL parents in the endosperm and is speculated to be a potential candidate gene for qPC2-2. This study will contribute to further research on the mechanisms underlying the regulation of maize PC, while also providing a genetic basis for marker-assisted selection in the future.

Summary: The functional tight junctions’ integrity plays an important role in liver physiology. A variety of liver diseases have been associated with the perturbation of tight junctions. Herein, we showed that the lower expression of α5 integrin in hepatocytes in patients with liver cirrhosis is associated with matrix deposition in the space of Disse. Selective silencing of α5 integrin in hepatocytes compromised the ultrastructure of tight junctions by downregulating claudin 1 in an SRC (proto-oncogene, non-receptor tyrosine kinase) signaling-dependent manner. α5 integrin signaling induced SRC-TET-mediated changes in 5-hydroxymethylcytosine and 5-methylcytosine levels in hepatocytes in vitro and in vivo. hMeDIP sequencing showed intergenic hypohydroxymethylation of the claudin 1 gene in hepatocytes after α5 integrin silencing in mice. Therefore, understanding the mechanisms regulating hepatic tight junction integrity in which α5 integrin-SRC signaling and epigenetic modifications cooperate might help advance the development of useful diagnostics and therapeutic approaches for liver disease.

ObjectivePolymyxins are currently the last line of defense in the treatment of carbapenem-resistant organisms (CRO). As a kind of polymyxin available for clinical use in China, we aim to explore the efficacy and safety of colistin sulfate (Polymyxin E sulfate, PES) in this study.MethodsThis real-world retrospective study included 119 patients diagnosed with CRO infection and treated with PES for more than 72 h, from May 2020 to July 2022 at West China Hospital. The primary outcome was clinical efficacy at the end of treatment, and secondary outcomes included microbial response, in-hospital mortality and incidence of nephrotoxicity.ResultsThe effective clinical and microbiological responses were 53.8% and 49.1%, respectively. And the in-hospital mortality was 27.7%. Only 9.2% of patients occurred with PES-related nephrotoxicity. Multivariate analysis revealed that duration of PES was an independent predictor of effective therapy, while age-adjusted Charlson comorbidity index (aCCI) and post-treatment PCT(p-PCT) were independent risk factors for poor outcome.ConclusionsPES can be a salvage treatment for CRO-induced infections with favorable efficacy and low nephrotoxicity. The treatment duration of PES, aCCI and p-PCT were factors related to the clinical effectiveness of PES.

Abstract Sociality is known to be capable of slowing individual senescence, but it is unclear whether the effect differs for reproduction versus survival in a sex‐specific manner. Here we predict that social benefits are directed toward (1) somatic maintenance in harsh environments where high survival prospects of adults over young intensify the trade‐off between current and future reproduction, and (2) females that invest more in reproduction and have a greater marginal effect if their survival is improved by reducing the cost of reproduction. These two predictions are tested with cooperatively breeding Tibetan ground tits (Pseudopodoces humilis). Across the lifetime, both mothers and fathers with helpers did not differ in brood size at fledging from their counterparts without helpers. The presence of helpers reduced survival senescence of both parents, but mothers benefited more than fathers from receiving help. Consequently, the inherent sex difference in life span and along with lifetime reproductive success, as expressed in breeders of never‐receiving help, became no longer obvious. The model of social modulation for senescence should facilitate the persistence of cooperative breeding in challenging environments.

Current toxicology research on nanoplastics (NPs) generally uses commercial spherical NPs. However, the physicochemical characteristics of commercial NPs are significantly different from those of NPs formed under natural conditions, possibly affecting the validity of the results. In analytical chemistry, a reference sample is selected such that its physicochemical properties are as similar as possible to the target. Therefore, a simulated “natural” NP synthesized in the laboratory that closely resembles naturally derived NPs would be used as an authentic standard. Here, we established the assay of scanning electron microscope (SEM)-particle size distribution analyzer (PSDA)-surface-enhanced Raman scattering (SERS) to detect NPs and prepared simulated “natural” NPs from polypropylene food packaging material using a method that mimics natural conditions. Nanofiltration was used to isolate three sets of simulated NPs with particle sizes ranging from 50–100 nm, 100–200 nm, and 200–400 nm. These simulated “natural” NPs were more similar to naturally occurring counterparts when compared with commercial NPs. These new standard NPs, which should be scalable for large-scale use, will improve the accuracy, reliability, and translatability of toxicological studies of NPs.

The availability of cadmium (Cd) in soils is an important factor affecting the safe production of crops. The application of certain soil amendments could reduce the soil Cd availability via the passivation of Cd. However, the passivation of Cd in alkaline soils is limited. Thus, different inorganic and organic amendments and their compound treatments were selected as passivators for reducing the Cd availability in a weakly alkaline farmland soil. The effects of different single and compound amendments on the soil pH and Cd availability, as well as the interactions between inorganic and organic components in immobilizing Cd, were evaluated. The results showed that the inorganic–organic compound amendments can considerably improve the Cd passivation efficiency in the weakly alkaline soil. Moreover, the inorganic and organic components in the compound amendments exerted different synergistic effects in Cd passivation. The manganese dioxide-based compound amendments showed the most remarkable synergistic effects, while the calcium–magnesium–phosphate fertilizer-based compound amendments displayed the weakest synergistic effects. The underlying mechanisms regarding the synergistic effects may be that the compound amendments enhanced the adsorption/specific adsorption, co-precipitation, and surface complexation of Cd in the alkaline soil. A more balanced recommendation for Cd immobilization in the weakly alkaline soil may be manganese dioxide-based compound amendments, given the synergistic effects and Cd immobilization capabilities of various compound materials. This study may provide a theoretical foundation for the passivation remediation of alkaline Cd-contaminated farmland soils by using inorganic–organic compound amendments.

Arid and semiarid wetlands, the core geographical unit of desert oases, significantly benefit and improve the ecological environment. In this study, we systematically compared the spatiotemporal dynamics and driving forces of natural and constructed wetlands in arid and semiarid regions of northern China from 1995 to 2019. For these comparisons, we utilized a land-use transition matrix, partial least-squares–structural equation model (PLS-SEM), and geographically weighted regression (GWR) model. The results showed that (1) the area of wetlands as a whole showed an upward trend, with natural and constructed wetlands increasing by 4.16% and 11.86%, respectively. The increases mainly resulted from conversions of grassland and other lands (shrub, sparse vegetation, and bare land). (2) The direct dominant factors that drove natural wetland changes were soil and terrain, while those that drove constructed wetlands were human disturbances. Human disturbance, by affecting soil, had a higher significant indirect effect on natural wetlands. Heat, by affecting moisture, had the greatest indirect effect on constructed wetlands. (3) The sensitivity of natural and constructed wetlands to the responses of different drivers showed significant spatial heterogeneity. This study explores the interaction and driving mechanisms of human and natural attributes on natural and constructed wetlands and provides a scientific foundation for the restoration and sustainable development of wetlands in arid and semiarid areas.

TiAl alloys are difficult to obtain high density through traditional pressing and sintering process. Sn is a promising liquid-phase sintering addition for TiAl alloys; however, the further studies have elaborated that the liquid phase sintering of Sn is limited due to poor wettability between TiAl and melt Sn. Based on it, this study adopts Sn–Al powder addition instead of pure Sn powder. The results describe that a small amount of active Al enhanced the wettability of the Sn droplets to the TiAl matrix, thereby further promoting the liquid phase sintering effect of the addition of Sn. The sample sintered at 1320–1350 °C has a density excess of 95%, near γ or duplex microstructure with small proportion of lamellar colonies. Through subsequent non-encapsulation HIP, the fine-grained structure is maintained at the same time to reach full density, which enables the as-sintered samples to obtain moderate tensile properties at room temperatures (UST = 520 ± 5 MPa, YS = 401 ± 7 MPa, EL = 1.33 ± 0.1).

Abstract Heterotopic ossification (HO) represents a common problem after tendon injury with no effective treatment yet being developed. Tenomodulin (Tnmd), the best-known mature marker for tendon lineage cells, has important effects in tendon tissue aging and function. We have reported that loss of Tnmd leads to inferior early tendon repair characterized by fibrovascular scaring and therefore hypothesized that its lack will persistently cause deficient repair during later stages. Tnmd knockout (Tnmd −/− ) and wild-type (WT) animals were subjected to complete Achilles tendon surgical transection followed by end-to-end suture. Lineage tracing revealed a reduction in tendon-lineage cells marked by ScleraxisGFP, but an increase in alpha smooth muscle actin myofibroblasts in Tnmd − /− tendon scars. At the proliferative stage, more pro-inflammatory M1 macrophages and larger collagen II cartilaginous template were detected in this group. At the remodeling stage, histological scoring revealed lower repair quality in the injured Tnmd −/− tendons, which was coupled with higher HO quantified by micro-CT. Tendon biomechanical properties were compromised in both groups upon injury, however we identified an abnormal stiffening of non-injured Tnmd −/ − tendons, which possessed higher static and dynamic E-moduli. Pathologically thicker and abnormally shaped collagen fibrils were observed by TEM in Tnmd −/− tendons and this, together with augmented HO, resulted in diminished running capacity of Tnmd −/− mice. These novel findings demonstrate that Tnmd plays a protecting role against trauma-induced endochondral HO and can inspire the generation of novel therapeutics to accelerate repair.

Abstract Background Lymphovascular space invasion (LVSI) is the first step of hematogenous metastasis. Exploration of the differential miRNA expression profiles between LVSI-positive and LVSI-negative ovarian cancer tissues may help to identify key miRNAs involved in the hematogenous metastasis of ovarian cancer. This study is aimed to identify microRNAs (miRNAs) that are differentially expressed between LVSI-positive and LVSI-negative ovarian cancer tissues, followed by exploring their association with bevacizumab response in ovarian cancer patients. Methods The Cancer Genome Altas (TGGA) dataset was used to identify the differentially expressed miRNAs between LVSI-positive and LVSI-negative ovarian cancer tissues. The prognostic value of the differentially expressed miRNAs was determined using GSE140082 dataset. Results We showed that miR-25 and miR-142 were differentially expressed between LVSI-positive and LVSI-negative ovarian cancer tumors. Kaplan-Meier analysis indicated that high miR-25 expression was associated with increased progression free survival (PFS) and extended overall survival (OS). Moreover, patients with low miR-25 expression benefited significantly from bevacizumab treatment in terms of PFS. A similar trend was observed in terms of OS though without reaching statistical significance. In contrast, no significant survival benefits from bevacizumab were observed in patients with high miR-25 expression in terms of PFS and OS. There was no significant correlation between miR-142 expression and PFS. In contrast, high miR-142 expression was associated with reduced OS. Moreover, patients with high miR-142 expression benefited significantly from bevacizumab treatment in terms of PFS and OS. However, bevacizumab treatment conferred no significant improvements in both PFS and OS in patients with low miR-142 expression. The nomogram for PFS indicated that miR-25 expression had a larger contribution to PFS than debulking status and bevacizumab treatment. And the nomogram for OS illustrated both miR-25 expression and miR-142 expression as sharing a larger contribution to OS than bevacizumab treatment and debulking status. Conclusion In conclusion, miR-25 expression correlates with a better PFS and OS in ovarian cancer. Patients with low miR-25 expression and high miR-142 expression could benefit from bevacizumab treatment significantly.

Abstract. Background:. Since the outbreak of coronavirus disease 2019 (COVID-19), human mobility restriction measures have raised controversies, partly because of the inconsistent findings. An empirical study is promptly needed to reliably assess the causal effects of the mobility restriction. The purpose of this study was to quantify the causal effects of human mobility restriction on the spread of COVID-19. Methods:. Our study applied the difference-in-difference (DID) model to assess the declines of population mobility at the city level, and used the log–log regression model to examine the effects of population mobility declines on the disease spread measured by cumulative or new cases of COVID-19 over time after adjusting for confounders. Results:. The DID model showed that a continual expansion of the relative declines over time in 2020. After 4 weeks, population mobility declined by −54.81% (interquartile range, −65.50% to −43.56%). The accrued population mobility declines were associated with the significant reduction of cumulative COVID-19 cases throughout 6 weeks (ie, 1% decline of population mobility was associated with 0.72% [95% CI: 0.50%–0.93%] reduction of cumulative cases for 1 week, 1.42% 2 weeks, 1.69% 3 weeks, 1.72% 4 weeks, 1.64% 5 weeks, and 1.52% 6 weeks). The impact on the weekly new cases seemed greater in the first 4 weeks but faded thereafter. The effects on cumulative cases differed by cities of different population sizes, with greater effects seen in larger cities. Conclusions:. Persistent population mobility restrictions are well deserved. Implementation of mobility restrictions in major cities with large population sizes may be even more important.

While incomplete non-medical data has been integrated into prediction models for epidemics, the accuracy and the generalizability of the data are difficult to guarantee. To comprehensively evaluate the ability and applicability of using social media data to predict the development of COVID-19, a new confirmed case prediction algorithm improving the Google Flu Trends algorithm is established, called Weibo COVID-19 Trends (WCT), based on the post dataset generated by all users in Wuhan on Sina Weibo. A genetic algorithm is designed to select the keyword set for filtering COVID-19 related posts. WCT can constantly outperform the highest average test score in the training set between daily new confirmed case counts and the prediction results. It remains to produce the best prediction results among other algorithms when the number of forecast days increases from one to eight days with the highest correlation score from 0.98 (P ​< 0.01) to 0.86 (P ​< 0.01) during all analysis period. Additionally, WCT effectively improves the Google Flu Trends algorithm's shortcoming of overestimating the epidemic peak value. This study offers a highly adaptive approach for feature engineering of third-party data in epidemic prediction, providing useful insights for the prediction of newly emerging infectious diseases at an early stage.

Prognosis prediction is difficult in hepatocellular carcinoma (HCC) due to high heterogeneity and complex etiology. It has recently been discovered that cuproptosis is a type of programmed cell death. However, its significance for HCC is still unclear. We analyzed mRNA expression profiles and clinical information from public databases to determine whether cuproptosis-related genes are associated with improved prognoses for HCC patients. The training cohort consisted of HCC patients from The Cancer Genome Atlas (TCGA), and the validation cohort relied on the International Cancer Genome Consortium (ICGC) database. We constructed a signature containing four genes using the least absolute shrinkage and selection operator (LASSO) COX regression model for calculating risk scores. Two risk groups were formed based on the median score. A significant improvement in survival was observed in the low-risk group compared to the high-risk. The multivariate Cox regression analysis showed that the risk score was an independent predictor of overall survival (OS). Further confirmation of the predictive accuracy of this signature is provided by receiver operating characteristic (ROC) analysis. Functional analysis revealed differences in immune status between the two risk groups. All the results described above were confirmed in the validation cohort. Therefore, a novel cuproptosis-related signature has the potential as a prognostic biomarker for HCC patients. Drugs developed to target cuproptosis-related genes may open up new pathways for treating HCC.

Vaccination is one of the most vigorous ways to intervene in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Cases of autoimmune hepatitis (AIH) after coronavirus disease (COVID-19) vaccination have been increasingly reported. Twenty-seven cases of AIH are summarized in this study, providing emerging evidence of autoimmune reactions in response to various COVID-19 vaccines, including in patients with special disease backgrounds such as primary sclerosing cholangitis (PSC), liver transplantation, and previous hepatitis C virus (HCV) treatment. Molecular mimicry, adjuvants, epitope spreading, bystander activation, X chromosome, and sceptical hepatotropism of SARS-CoV-2 may account for, to some extent, such autoimmune phenomena. Immunosuppressive corticosteroids perform well with or without azathioprine in such post-COVID-19-vaccination AIH. However, determination of the exact mechanism and establishment of causality require further confirmation.

The heat transfer characteristics of the wall formed by the aluminum extrusion and multi insulation material layers are studied experimentally and numerically. The experimental results show that the equivalent thermal conductivity of the wall does not depend on the temperature difference and its position regarding to the gravity direction. These results indicate that the roles of the natural convection and the radiation heat transfer in the aluminum extrusion are very weak, which are confirmed by the numerical results. The numerical results show that the aluminum extrusion formed by the aluminum tape with thickness less than 5% of the wall thickness transfers more than 99% of the total heat transferred through the combined layer. As resulting, a more uniform temperature distribution is obtained on the surface in contact with the air in the aluminum extrusion. The results suggest that the natural convection and heat radiation in the combined layer can be safely ignored.

IntroductionParathyroid carcinoma (PC) is a very rare endocrine malignancy occurring in less than 1% of all cases of primary hyperparathyroidism (pHPT). The liver is the second most common target organ for distant metastases of PC, but no guidelines are available for the diagnosis and treatment of liver metastases. In this study, we attempted to summarize the characteristics of the diagnosis and treatment of liver metastases based on our patients and other cases reported in the literature.Materials and methodsThe files of all patients diagnosed with PC with liver metastases summarized at our center between 2000 and 2022 were reviewed, and three datasets from Medline, Web of Science, and Embase were systematically searched to identify relevant articles.ResultsThree patients with liver metastases from our center and 11 patients from the literature were included in the study. All patients had pHPT with borderline remission of hypercalcemia after each operation. A total of 71.4% of the patients’ liver lesions were found by abdominal CT scans, while 35.7% were found by MRI, PET-CT, and fine-needle aspiration biopsy (FNAB), which were also helpful for diagnosis. Eight of nine patients (88.9%) who underwent surgery, radiofrequency ablation (RFA), or transcatheter arterial embolization (TAE) were alive, and only one postoperative patient died after a follow-up of 60 months.ConclusionsPC is a rare malignant tumor prone to recurrence and metastasis, and postoperative reviews should be carried out routinely. Abnormally elevated parathyroid hormone (PTH) and serum calcium can indicate recurrence or metastasis. Enhanced CT and MRI can provide valuable support for the diagnosis of liver metastases, but whether [18F]FDG-PET-CT, [18F]FCH-PET-CT, or [11C]choline-PET-CT can be used as a diagnostic basis requires further study. Resection of liver metastases, segmental hepatectomy, or RFA can significantly improve patients’ symptoms.