Search

Abstract The advent of immunotherapy has greatly improved the prognosis of non-small cell lung (NSCLC) patients. However, given its low response rate and high cost of treatment, the search for valuable predictive markers of treatment efficacy is necessary. Considering the complexity and heterogeneity of the tumour and tumour microenvironment, the construction of a multi-dimensional prediction model is necessary. Therefore, we aimed to integrate clinical parameters, radiomic features, and immune signature data from NSCLC patients receiving immunotherapy to construct a multi-dimensional prediction model to better predict the efficacy of immunotherapy. The current study enrolled 137 NSCLC patients who received immunotherapy. We collected baseline clinical information, CT images, and tumour tissue specimens. Using 3D-Slicer software, radiomic features were extracted from patient CT images, and tumor tissue samples obtained before immunotherapy were subjected to immunohistochemical staining. Then, the least absolute shrinkage and selection operator (LASSO) Cox regression analysis was applied to downscale the data, and the radiomic features and immune signatures associated with the prognosis of immunotherapy patients were identified. The modified lung immune predictive index (mLIPI), radiomics score (Radioscore), immune score and multi-dimensional model nomogram were constructed. The C-index and area under the curve (AUC) were applied to evaluate the predictive efficacy of the models. Three radiomic features and three immune signatures that could predict the efficacy of immunotherapy were eventually screened. Multivariate analysis showed that the mLIPI, Radioscore, and immune score were independent predictive factors for PFS and OS (P

Abstract Background The prevalence of multiple nosocomial infections (MNIs) is on the rise, however, there remains a limited comprehension regarding the associated risk factors, cumulative risk, probability of occurrence, and impact on length of stay (LOS). Method This multicenter study includes all hospitalized patients from 2020 to July 2023 in two sub-hospitals of a tertiary hospital in Guangming District, Shenzhen. The semi-Markov multi-state model (MSM) was utilized to analyze risk factors and cumulative risk of MNI, predict its occurrence probability, and calculate the extra LOS of nosocomial infection (NI). Results The risk factors for MNI include age, community infection at admission, surgery, and combined use of antibiotics. However, the cumulative risk of MNI is lower than that of single nosocomial infection (SNI). MNI is most likely to occur within 14 days after admission. Additionally, SNI prolongs LOS by an average of 7.48 days (95% Confidence Interval, CI: 6.06–8.68 days), while MNI prolongs LOS by an average of 15.94 days (95% CI: 14.03–18.17 days). Furthermore, the more sites of infection there are, the longer the extra LOS will be. Conclusion The longer LOS and increased treatment difficulty of MNI result in a heavier disease burden for patients, necessitating targeted prevention and control measures.

IntroductionAgronomic traits are key components of wheat yield. Exploitation of the major underlying quantitative trait loci (QTLs) can improve the yield potential in wheat breeding.MethodsIn this study, we constructed a recombinant inbred line (RIL) population from Mingxian 169 (MX169) and Pindong 34 (PD34) to determine the QTLs for grain length (GL), grain width (GW), grain length-to-width ratio (LWR), plant height (PH), spike length (SL), grain number per spike (GNS), and the thousand grain weight (TGW) across four environments using wheat 90K SNP array.ResultsA QTL associated with TGW, i.e., QTGWpd.swust-6BS, was identified on chromosome 6B, which explained approximately 14.1%–16.2% of the phenotypic variation. In addition, eight QTLs associated with GL were detected across six chromosomes in four different test environments. These were QGLpd.swust-1BL, QGLpd.swust-2BL, QGLpd.swust-3BL.1, QGLpd.swust-3BL.2, QGLpd.swust-5DL, QGLpd.swust-6AL, QGLpd.swust-6DL.1, and QGLpd.swust-6DL.2. They accounted for 9.0%–21.3% of the phenotypic variation. Two QTLs, namely, QGWpd.swust-3BS and QGWpd.swust-6DL, were detected for GW on chromosomes 3B and 6D, respectively. These QTLs explained 12.8%–14.6% and 10.8%–15.2% of the phenotypic variation, respectively. In addition, two QTLs, i.e., QLWRpd.swust-7AS.1 and QLWRpd.swust-7AS.2, were detected on chromosome 7A for the grain LWR, which explained 10.9%–11.6% and 11.6%–11.2% of the phenotypic variation, respectively. Another QTL, named QGNSpd-swust-6DS, was discovered on chromosome 6D, which determines the GNS and which accounted for 11.4%–13.8% of the phenotypic variation. Furthermore, five QTLs associated with PH were mapped on chromosomes 2D, 3A, 5A, 6B, and 7B. These QTLs were QPHpd.swust-2DL, QPHpd.swust-3AL, QPHpd.swust-5AL, QPHpd.swust-6BL, and QPHpd.swust-7BS, which accounted for 11.3%–19.3% of the phenotypic variation. Lastly, a QTL named QSLpd.swust-3AL, conferring SL, was detected on chromosome 3A and explained 16.1%–17.6% of the phenotypic variation. All of these QTLs were defined within the physical interval of the Chinese spring reference genome.DiscussionThe findings of this study have significant implications for the development of fine genetic maps, for genomic breeding, and for marker-assisted selection to enhance wheat grain yield.

Abstract Aim This study aimed to explore the relationship between nurses' occupational exposure to antineoplastic agents and adverse pregnancy outcomes. Design Meta‐analysis. Methods Data were retrieved from studies published before April 2022 in PubMed, the Cochrane Library, the Web of Science, Embase databases, the China National Knowledge Infrastructure (CNKI), China Biology Medicine disc (CBM), China Science and Technology Journal databases (VIP) and Wan Fang databases (WF). Stata MP (Version 17.0) was used to conduct this meta‐analysis. Results The current evidence shows that occupational exposure to antineoplastic agents increases nurses' risk of spontaneous abortions, stillbirths, and congenital abnormalities. It is necessary to pay attention to occupational exposures caused by antineoplastic agents, especially for female nurses of reproductive age. Managers should take timely and effective countermeasures to ensure their occupational safety and reduce the risk of adverse pregnancy outcomes.

Abstract The liver is an immune organ that plays a vital role in the detection, capture, and clearance of pathogens and foreign antigens that invade the human body. During acute and chronic infections, the liver transforms from a tolerant to an active immune state. The defence mechanism of the liver mainly depends on a complicated network of intrahepatic and translocated immune cells and non-immune cells. Therefore, a comprehensive liver cell atlas in both healthy and diseased states is needed for new therapeutic target development and disease intervention improvement. With the development of high-throughput single-cell technology, we can now decipher heterogeneity, differentiation, and intercellular communication at the single-cell level in sophisticated organs and complicated diseases. In this concise review, we aimed to summarise the advancement of emerging high-throughput single-cell technologies and re-define our understanding of liver function towards infections, including hepatitis B virus, hepatitis C virus, Plasmodium, schistosomiasis, endotoxemia, and corona virus disease 2019 (COVID-19). We also unravel previously unknown pathogenic pathways and disease mechanisms for the development of new therapeutic targets. As high-throughput single-cell technologies mature, their integration into spatial transcriptomics, multiomics, and clinical data analysis will aid in patient stratification and in developing effective treatment plans for patients with or without liver injury due to infectious diseases.

Background Information about orthopedics diseases on the Internet has not been extensively assessed. Our purpose was to evaluate the quality of online information of osteosarcoma on current video-sharing platforms in mainland China. Method TikTok and Bilibili were independently queried from June to July 2023 by four independent researchers using the Microsoft Edge web browser. Information about the videos and creators was recorded, and descriptive analyses were conducted. Results After data extraction, a total of 95 videos were included, in which 43 videos were uploaded by certified doctors (45.3%), with 35 videos (36.8%) uploaded by certified orthopedic surgeons. Of the content of these videos, 78.9% were introduction ( n = 75), 64.2% were on professional knowledge ( n = 61), 28.4% were on treatment ( n = 27), while 5.3% were on surgical techniques ( n = 5). The mean DISCERN total score was 43.8 ± 13.4, and the mean JAMA score was 3.8 ± 0.3. Conclusions Videos about osteosarcoma on current video-sharing platforms were extensive, but were not comprehensive and professional. Although current online videos have the potential to improve public awareness on osteosarcoma, due to their quality and content, were not assessed to be good sources for medical education.

Abstract Background Clear cell type hepatocellular carcinoma (HCC) is an uncommon neoplasm with an ambivalent prognosis compared to common type HCC. Methods First, patients with clear cell or common type HCC were enrolled from the Surveillance, Epidemiology, and End Results (SEER) database, and their demographic and clinical characteristics were identified. Next, overall survival (OS), disease‐specific survival (DSS), and subgroup analysis of the two types of HCC were performed. Next, we utilized a competing risk model to focus on cancer‐caused death. Finally, propensity score matching (PSM) was employed to reduce the confounding factors based on the histopathological type, and sensitivity analysis was conducted. Results A total of 205 cases of clear cell type HCC and 29,954 cases of common type HCC were enrolled in our study. Patients with clear cell type HCC were older and predominantly female than those with common type HCC. OS and DSS were not significantly different between the two groups, and histopathological type was not a prognostic factor of HCC, as verified by the competing risk model. Patient characteristics adjusted by PSM and sensitivity analysis confirmed this conclusion. In subgroup analysis, patients with clear cell type HCC at grade III ~ IV and with lymph nodes metastasis had a better prognosis compared to common type HCC. Conclusions This study revealed that the prognosis of clear cell type HCC is similar to common type HCC. Tumor differentiation grade and status of lymph node metastasis affect the prognosis of HCC.

Abstract Background and aim Patients with autism spectrum disorder (ASD) commonly experience aberrant skin sensation sensitivity; however, the causal relationship is not yet clear. This study uses a bidirectional Mendelian randomization (MR) method to explore the relationship between disturbance of skin sensation (DSS) and ASD. Methods Single‐nucleotide polymorphisms (SNPs) extracted from the summary data of genome‐wide association studies were used as genetic instruments. MR was performed using the inverse‐variance‐weighted method, with alternate methods (e.g., weighted median, MR‐Egger, simple mode, weighted mode, and MR‐pleiotropy residual sum and outlier) and multiple sensitivity analyses to assess horizontal pleiotropy and remove outliers. Results The results of the analysis using six SNPs as genetic instruments showed that the DSS is associated with an increased risk of ASD (odds ratio = 1.126, 95% confidence interval = 1.029–1.132; p = .010). The results of the sensitivity analyses were robust with no evidence of pleiotropy. The reverse MR analyses showed no causal effects of ASD on DSS. Conclusion This study's findings suggest that DSS has potential causal effects on ASD, whereas ASD has no effect on DSS. Thus, skin sensitivity may represent a behavioral marker of ASD, by which some populations could be subtyped in the future.

BackgroundThe prevalence of family dysfunction, anxiety and depression is high in people with disabilities due to long-term activity constraints and social difficulties. Recently, although studies have attempted to provide guidance for family therapy by focusing on the relationship between family function and negative emotions, the specific effects of improved family function during family therapy on alleviation of anxiety and depressive symptoms have been obscured. Thus, this study attempted to elucidate the impact of specific family functioning on specific symptoms of anxiety and depression through network analysis.MethodsFamily APGAR Index Questionnaire (APGAR), Generalized Anxiety Scale (GAD-7), and Patient Health Questionnaire Depression Scale (PHQ-9) were used to survey 897 adults with disabilities in Sichuan Province. Meanwhile, network analysis for studying the relationship between anxiety, depression and family functioning among the disabled via R software.ResultsThe network analysis showed that (1) Nodes PHQ4 (“Energy”), APGAR3 (“Growth”), GAD1 (“Nervousness”) and GAD4 (“Relaxing Trouble”) were central nodes in the network model; (2) Bridge nodes linking family function, anxiety and depressive symptoms in the sample were PHQ9 (“Suicide ideation”), PHQ6 (“Worthlessness”), GAD1 (“Nervousness”) and GAD5 (“Restlessness”); (3) The node APGAR5 (“Resolve”) directly connects the bridge symptoms PHQ9 (“Suicide ideation”) and PHQ8 (“Motor”).ConclusionThis study suggests that therapists could target the resolve of family members during family therapy to reduce suicidal ideation and enhance the level of activity of people with disabilities, thereby improving the network of anxiety and depression symptoms and alleviating negative emotions of people with disabilities.

Abstract One year after the outbreak of COVID-19, medical staff are facing high anxiety due to multiple work stresses. Social support has become a protective factor for healthcare workers' anxiety symptoms, but the exact mechanism of action is not yet known. Based on the buffering model, this study aims to explore the impact and mechanisms of action of healthcare workers' perception of social support (PSS) on anxiety symptoms in the context of the epidemic and to further explore how the emotional characteristics of risk perception (ECRP) and resilience play their influence. To this end, this study measured 839 healthcare workers using an online questionnaire from 4 February to 1 March 2021. The results found that PSS among healthcare workers negatively predicted anxiety symptoms. ECRP partially mediated the relationship between PSS and anxiety symptoms, and resilience moderated the first half of the pathway in the model of PSS through ECRP on anxiety symptoms. The emotional characteristics of risk perception of COVID-19 in individuals with high resilience decrease significantly with the increase of PSS, while this change is not significant in individuals with low resilience.

Abstract Background The natural protoberberine jatrorrhizine (JA) is reported to have several medicinal properties and a significant effect on the gut microbiota of mice. The regulation of gut microbiota is generally known to play an important role in the intestinal mucosal immune response to ulcerative colitis (UC). However, whether JA can be used in the treatment of UC is still unclear. Our study aimed to investigate the underlying therapeutic effects and mechanisms of JA in treating colitis. Results Compared with the DSS-induced colitis model group, the JA + DSS treated group had more significant improvements in weight loss, disease activity index score, colon length shortening, and pathological inflammation. 16s rRNA sequencing analysis showed that JA treatment protected colitis mice against DSS-induced disturbance of gut microbiota. At the phylum level, reductions in Deferribacteres and Proteobacteria were observed in the JA-treated group; At the genus level, the JA-treated group showed an increased relative abundance of Akkermansia and decreased abundance of Escherichia-Shigella, Desulfovibrio, Mucispirillum, etc. Network pharmacology was then used to screen out five drug-disease target genes (NOS2, ESR1, CALM1, CALM2, CALM3). Transcriptomics analysis further validated that the NOS2 expression was significantly reduced in colon tissue of JA-administered mice compared with DSS control mice. Additionally, analysis of correlation suggested that NOS2 expression was negatively correlated with the relative abundance of AKKermansia and positively correlated with Desulfovibrio, Rikenella. Conclusion JA alleviates ulcerative colitis via regulating gut microbiota and NOS2 expression.

The Zα domain has a compact α/β architecture containing a three-helix bundle flanked on one side by a twisted antiparallel β sheet. This domain displays a specific affinity for double-stranded nucleic acids that adopt a left-handed helical conformation. Currently, only three Zα-domain proteins have been identified in eukaryotes, specifically ADAR1, ZBP1, and PKZ. ADAR1 is a double-stranded RNA (dsRNA) binding protein that catalyzes the conversion of adenosine residues to inosine, resulting in changes in RNA structure, function, and expression. In addition to its editing function, ADAR1 has been shown to play a role in antiviral defense, gene regulation, and cellular differentiation. Dysregulation of ADAR1 expression and activity has been associated with various disease states, including cancer, autoimmune disorders, and neurological disorders. As a sensing molecule, ZBP1 exhibits the ability to recognize nucleic acids with a left-handed conformation. ZBP1 harbors a RIP homotypic interaction motif (RHIM), composed of a highly charged surface region and a leucine-rich hydrophobic core, enabling the formation of homotypic interactions between proteins with similar structure. Upon activation, ZBP1 initiates a downstream signaling cascade leading to programmed cell death, a process mediated by RIPK3 via the RHIM motif. PKZ was identified in fish, and contains two Zα domains at the N-terminus. PKZ is essential for normal growth and development and may contribute to the regulation of immune system function in fish. Interestingly, some pathogenic microorganisms also encode Zα domain proteins, such as, Vaccinia virus and Cyprinid Herpesvirus. Zα domain proteins derived from pathogenic microorganisms have been demonstrated to be pivotal contributors in impeding the host immune response and promoting virus replication and spread. This review focuses on the mammalian Zα domain proteins: ADAR1 and ZBP1, and thoroughly elucidates their functions in the immune response.

Zanubrutinib is a Bruton tyrosine kinase (BTK) inhibitor used in B cell malignancy treatment and is generally well tolerated in most patients. Zanubrutinib-induced aseptic meningitis is currently not reported. Herein, we present the first case of zanubrutinib-induced aseptic meningitis. A 33-year-old woman was diagnosed with relapsed/refractory follicular lymphoma and subsequently developed aseptic meningitis after receiving zanubrutinib treatment. We reviewed the literature and uncovered the lack of current reports on zanubrutinib or other BTK inhibitor-induced aseptic meningitis. Moreover, we summarized cases on aseptic meningitis induced by common chemotherapy and targeted drugs used for hematological diseases. Drug-induced aseptic meningitis (DIAM) is a drug-induced meningeal inflammation. The possible pathogenesis is the direct stimulation of the meninges via intrathecal injection of chemotherapy drugs and immune hypersensitivity response caused by immunosuppressive drugs. It is more common in women with immune deficiency and mainly manifests as persistent headache and fever. Cerebrospinal fluid examinations mainly demonstrate a significant increase in cells and proteins. DIAM diagnosis needs to exclude bacterial, fungal, viral, and tuberculosis infections; neoplastic meningitis; and systemic diseases involving the meninges. The prognosis of DIAM is usually favorable, and physicians should detect and stop the causative drug. In conclusion, zanubrutinib-induced aseptic meningitis is a rare but serious complication, and physicians should be promptly aware of this adverse event to avoid serious consequences.

Abstract Single image dehazing, as a key prerequisite of high-level computer vision tasks, catches more and more attentions. Traditional model-based methods recover haze-free images via atmospheric scattering model, which achieve favorable dehazing effect but endure artifacts, halos, and color distortion. By contrast, recent learning-based methods dehaze images by a model-free way, which achieve better color fidelity but tend to acquire under-dehazed results due to lacking of knowledge guiding. To combine these merits, we propose a novel online knowledge distillation network for single image dehazing named OKDNet. Specifically, the proposed OKDNet firstly preprocesses hazy images and acquires abundant shared features by a multiscale network constructed with attention guided residual dense blocks. After that, these features are sent to different branches to generate two preliminary dehazed images via supervision training: one branch acquires dehazed images via the atmospheric scattering model; another branch directly establishes the mapping relationship between hazy images and clear images, which dehazes images by a model-free way. To effectively fuse useful information from these two branches and acquire a better dehazed results, we propose an efficient feature aggregation block consisted of multiple parallel convolutions with different receptive. Moreover, we adopt a one-stage knowledge distillation strategy named online knowledge distillation to joint optimization of our OKDNet. The proposed OKDNet achieves superior performance compared with state-of-the-art methods on both synthetic and real-world images with fewer model parameters. Project website: https://github.com/lanyunwei/OKDNet .

Excessive expansion of cholangiocytes in the liver leads to ductular reaction and liver disease. Here, the authors show that genetic ablation, or pharmacological inhibition, of biliary NIK blocks ductular reaction, liver inflammation, and liver fibrosis in mice by modulating secretion of cholangiokines that mediate liver inflammation and fibrosis.

Patients with heroin use disorder (HUD) often exhibit trait impulsivity, which may be an important factor in and a good predictor of addiction. However, the factor structure of HUD trait impulsivity (motor, attentional, and nonplanning) and its neural correlates are not yet known. A total of 24 male volunteers with HUD and 16 healthy control volunteers were recruited for this cross-sectional study. The Barratt Impulsiveness Scale (BIS-11) and resting-state functional magnetic resonance imaging (rs-fMRI) were employed using the insula as a seed point in an effort to understand the association between trait impulsivity and its intrinsic factors and functional connectivity (FC) between the insula and the whole brain. The HUD group in this study exhibited higher total trait impulsivity scores, motor impulsivity, and nonplanning impulsivity than the control group. Changes in FC between the right insula and the lateral occipital cortex and the right angular gyrus were significantly positively correlated with total trait impulsivity scores, motor impulsivity, and nonplanning impulsivity, whereas changes in the FC between the left insula and the left superior frontal gyrus and left frontopolar brain region were significantly negatively correlated with trait impulsivity. Thus, the insula may serve as an important biomarker for identifying trait impulsivity and its intrinsic factor structure in patients with HUDs.

Background and purposeAs Coronavirus disease (COVID-19) continues to spread around the world, COVID-19 vaccines are the most effective weapons against the global pandemic. Yet vaccine hesitancy remains a serious problem and can pose certain hazards to individuals' mental health, such as rising anxiety. Therefore, based on Self-Discrepancy Theory, this paper aims to explore the role of COVID-19 vaccine hesitancy on individual generalized anxiety disorder and its influence mechanisms through two studies.MethodsStudy one involved 654 Chinese participants using the Vaccine Hesitancy Questionnaire and the Generalized Anxiety Disorder 7-item (GAD-7) scale. In Study two, the Vaccine Hesitation Questionnaire, GAD-7 scale, Perceived Risk of COVID-19 pandemic scale, and Vaccination Status Questionnaire were used and data from 3,282 Chinese residents was collected.ResultsVaccine hesitancy directly increases generalized anxiety disorder; risk perception plays a partial mediating role between vaccine hesitancy and generalized anxiety disorder; vaccination status moderated vaccine hesitancy's effect on risk perception and generalized anxiety disorder.ConclusionVaccine hesitancy predicts generalized anxiety disorder through risk perception, but the mediating role of risk perception is moderated by vaccination status, which means that for the vaccinated group when their vaccine hesitancy is reduced, it will be easier to reduce the risk perception and thus the generalized anxiety disorder.

In order to improve the cavitation performance of the self-excited oscillation nozzle (SEON), a novel SEON with a circular arc curve chamber was designed by changing the chamber wall profile of the SEON. The performance of the circular arc curve chamber SEON was studied numerically. Taking the vapor volume distribution and the vapor volume fraction as the evaluation indexes, the influences of the chamber wall profile on the cavitation performance of the circular arc curve chamber SEON were analyzed. In addition, it was compared with the broken-line chamber SEON. The numerical results show that the cavitation performance of the circular arc curve chamber SEON is first enhanced and then weakened by increasing the circular arc radius. The circular arc curve chamber structure can form a larger central cavitation volume in the nozzle, which improves the cavitation performance of the SEON. When the circular arc radius is 2 mm, the cavitation area and the turbulent kinetic energy of the circular arc curve chamber SEON increase by 122.5% and 16.9%.

Acute liver failure (ALF) is a severe liver disease with a high mortality rate without effective therapeutic drugs. Ferroptosis is a form of programmed cell death that plays an important role in ALF. In this study, we aimed to identify ferroptosis-related genes in ALF, thereby predicting promising compounds to treat ALF. First, mRNA microarray data were utilized to identify the ferroptosis-related differentially expressed genes (DEGs). Hub genes were screened in the protein–protein interaction network and validated. Subsequently, potential drugs to treat ALF were predicted. One of the predicted drugs was tested in an ALF model of mice. Ferroptosis examination and molecular docking were analyzed to explore the mechanism. A total of 37 DEGs were identified, ten hub genes were extracted, and their expression in ALF was validated. The predicted drug niclosamide mitigated lipopolysaccharide/D-galactosamine-induced hepatotoxicity, and decreased mortality of mice in the ALF model. Mechanically, niclosamide may combine with signal transducer and activator of transcription 3 to inhibit ALF progression by suppressing ferroptosis. This study may help advance our understanding of the role of ferroptosis in ALF, and niclosamide may be promising for therapeutic efficacy in patients with ALF.

Objective： A method for simple and rapid determination of potassium content in cigarette paper will be built for workshops of cigarette factory. Methods: An ion-selective electrode method was used by comparing with the pretreatment methods for cigarette paper samples and potential response behaviors of potassium ion-selective electrodes in different buffer solutions. Results: The potassium ion selective electrode possessed excellent response performance for K+ in lithium acetate buffer solution （0.1 mol/L, pH 7.0） with a linear response range of 1.0×10-5 ~1.0×10-2 mol/L, a slope of 55.79 mV/dec （25 ℃）, and a lower limit of detection of 2.14×10-6 mol/L. The average relative standard deviations of the K+ selective electrode on cigarette paper samples were 0.55% for intra-day test and 2.8% for inter-day test, both less than 5%. The test results of the electrode method were in well agreement with that of ion chromatography, with an average relative deviation of 4.1% （n=10） and recoveries between 95.0% and 101.9%. It was demonstrated effectively through a consecutive test over one week. Conclusion: Among the pretreatment methods for cigarette paper samples, the ultrasonic extraction of potassium ions with 1% diluted acetic acid for 30 min has been found to be fast, simple and environmentally friendly. The ion-selective electrode method is accurate and reliable, which is suitable for the rapid detection of potassium in cigarette paper.

Abstract In recent decades, with the continuous development of high‐throughput sequencing technology, data volume in medical research has increased, at the same time, almost all clinical researchers have their own independent omics data, which provided a better condition for data mining and a deeper understanding of gene functions. However, for these large amounts of data, many common and cutting‐edge effective bioinformatics research methods still cannot be widely used. This has encouraged the establishment of many analytical platforms, a portion of databases or platforms were designed to solve the special analysis needs of users, for instance, MG RAST, IMG/M, Qiita, BIGSdb, and TRAPR were developed for specific omics research, and some databases or servers provide solutions for special problems solutions. Metascape was designed to only provide functional annotations of genes as well as function enrichment analysis; BioNumerics and RidomSeqSphere+ perform multilocus sequence typing; CARD provides only antimicrobial resistance annotations. Additionally, some web services are outdated, and inefficient interaction often fails to meet the needs of researchers, such as our previous versions of the platform. Therefore, the demand to complete massive data processing tasks urgently requires a comprehensive bioinformatics analysis platform. Hence, we have developed a website platform, Sangerbox 3.0 (http://vip.sangerbox.com/), a web‐based tool platform. On a user‐friendly interface that also supports differential analysis, the platform provides interactive customizable analysis tools, including various kinds of correlation analyses, pathway enrichment analysis, weighted correlation network analysis, and other common tools and functions, users only need to upload their own corresponding data into Sangerbox 3.0, select required parameters, submit, and wait for the results after the task has been completed. We have also established a new interactive plotting system that allows users to adjust the parameters in the image; moreover, optimized plotting performance enables users to adjust large‐capacity vector maps on the web site. At the same time, we have integrated GEO, TCGA, ICGC, and other databases and processed data in batches, greatly reducing the difficulty to obtain data and improving the efficiency of bioimformatics study for users. Finally, we also provide users with rich sources of bioinformatics analysis courses, offering a platform for researchers to share and exchange knowledge.

Total sleep deprivation (TSD) leads to cognitive decline; however, the neurophysiological mechanisms underlying resting-state electroencephalogram (EEG) changes after TSD remain unclear. In this study, 42 healthy adult participants were subjected to 36 h of sleep deprivation (36 h TSD), and resting-state EEG data were recorded at baseline, after 24 h of sleep deprivation (24 h TSD), and after 36 h TSD. The analysis of resting-state EEG at baseline, after 24 h TSD, and after 36 h TSD using source localization analysis, power spectrum analysis, and functional connectivity analysis revealed a decrease in alpha-band power and a significant increase in delta-band power after TSD and impaired functional connectivity in the default mode network, precuneus, and inferior parietal lobule. The cortical activities of the precuneus, inferior parietal lobule, and superior parietal lobule were significantly reduced, but no difference was found between the 24 h and 36 h TSD groups. This may indicate that TSD caused some damage to the participants, but this damage temporarily slowed during the 24 h to 36 h TSD period.

Acute myocardial infarction (AMI) has a high mortality. The single-cell RNA sequencing (scRNA-seq) method was used to analyze disease heterogeneity at the single-cell level. From the Gene Expression Omnibus (GEO) database (GSE180678), AMI scRNA-seq were downloaded and preprocessed by the Seurat package. Gene expression data came from GSE182923. Cell cluster analysis was conducted. Cell types were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were performed on hub genes. Drugs were predicted by protein–protein interaction (PPI) and molecular docking. In total, 7 cell clusters were defined based on the scRNA-seq dataset, and the clusters were labeled as 5 cell types by marker genes. Hematopoietic stem cell types as a differential subgroups were higher in AMI than in healthy tissues. From available databases and PPI analysis, 52 common genets were identified. Based on 52 genes, 5 clusters were obtained using the MCODE algorithm, and genes in these 5 clusters involved in immune and inflammatory pathways were determined. Correlation analysis showed that hematopoietic stem cell types were negatively correlated with ATM, CARM1, and CASP8 but positively correlated with CASP3 and PPARG. This was reversed with immune cells. Molecular docking analysis showed that DB05490 had the lowest docking score with PPARG. We identified 5 hub genes (ATM, CARM1, CASP8, CASP3, and PPARG) involved in AMI progression. Compound DB05490 was a potential inhibitor of PPAG.

Enhancing thermal conductivity coefficient (λ) of liquid crystal polyesters would further widen their application in electronics and electricals. In this work, a kind of biphenyl-based dihydroxy monomer is synthesized using 4, 4’-biphenyl (BP) and triethylene glycol (TEG) as raw material, which further reacts with three different dicarboxylic acids (succinic acid, p-phenylenediacetic acid, and terephthalic acid, respectively) by melt polycondensation to prepare intrinsically highly thermally conductive poly 4’, 4”’-[1, 2-ethanediyl-bis(oxy-2, 1-ethanediyloxy)]-bis(p-hydroxybiphenyl) succinate (PEOS), poly 4’, 4”’-[1, 2-ethanediyl-bis(oxy-2, 1-ethanediyloxy)]-bis(p-hydroxybiphenyl) p-phenyldiacetate (PEOP) and poly 4’, 4”’-[1, 2-ethanediyl-bis(oxy-2, 1-ethanediyloxy)]-bis(p-hydroxybiphenyl) terephthalate (PEOT), collectively called biphenyl-based liquid crystal polyesters (B-LCPE). The results show that B-LCPE possess the desired molecular structure, exhibit smectic phase in liquid crystal range and semicrystalline polymers at room temperature, and possess excellent intrinsic thermal conductivities, thermal stabilities, and mechanical properties. λ of PEOT is 0.51 W/(m·K), significantly exceeds that of polyethylene terephthalate (0.15 W/(m·K)) which has similar molecular structure with PEOT, and also higher than that of PEOS (0.32 W/(m·K)) and PEOP (0.38 W/(m·K)). The corresponding heat resistance index (THRI), elasticity modulus, and hardness of PEOT are 174.6°C, 3.6 GPa, and 154.5 MPa, respectively, and also higher than those of PEOS (162.2°C, 1.8 GPa, and 83.4 MPa) and PEOP (171.8°C, 2.3 GPa, and 149.6 MPa).

Menopause is accompanied with an increased risk of cardiovascular disease. DNA methylation may have a significant impact on postmenopausal women’s development of coronary heart disease. DNA methylation alterations in peripheral blood mononuclear cells (PBMCs) from women with coronary heart disease and healthy controls were detected using the Illumina Infinium MethylationEPIC BeadChip platform in this work. We employed Sangerbox technology and the GO and KEGG databases to further study the pathogenesis of coronary heart disease in postmenopausal women. After that, we used functional epigenetic module analysis and Cytoscape to remove the hub genes from the protein–protein interaction networks. Five genes (FOXA2, PTRD, CREB1, CTNAP2, and FBN2) were the hub genes. Lipid accumulation, endothelial cell failure, inflammatory responses, monocyte recruitment and aggregation, and other critical biological processes were all influenced by these genes. Finally, we employed methylation-specific PCR to demonstrate that FOXA2 was methylated at a high level in postmenopausal women with coronary heart disease. To better understand coronary heart disease in postmenopausal women’s molecular mechanisms, our study examine the major factors contributing to the state of DNA methylation modification, which will help discover novel diagnostic tools and treatment options.

Background: Previous studies revealed that sleep deprivation (SD) impairs risk perception and leads to poor decision-making efficiency. However, how risk perception is related to brain regions’ communication after SD has not been elucidated. In this study, we investigated the neuropsychological mechanisms of SD-impaired risk perception. Methods: Nineteen healthy male adults were recruited and underwent resting-state functional magnetic resonance imaging during a state of rested wakefulness and after nearly 36 h of total SD. They then completed the balloon analog risk task, which was used to measure the risk perception ability of risky decision-making. Regional homogeneity (ReHo) and voxel-wise functional connectivity were used to investigate neurobiological changes caused by SD. Correlation analysis was used to investigate the relationship between changes in ReHo, function, and risk perception. Results: At the behavioral level, risk perception decreased after 36 h of SD. At the neural level, SD induced a significant increase in ReHo in the right postcentral gyrus and was positively correlated with risk perception changes. The functional connectivity between the right postcentral gyrus, left medial temporal gyrus, and right inferior temporal gyrus was enhanced. Critically, increased right postcentral gyrus and right inferior temporal gyrus connectivity positively correlated with changes in risk perception. Conclusions: SD impairs the risk perception associated with altered postcentral connectivity. The brain requires more energy to process and integrate sensory and perceptual information after SD, which may be one possible reason for decreased risk perception ability after SD.

The submerged cavitation jet is suitable for ocean engineering activities such as ship fouling cleaning, organic wastewater treatment, offshore oil drilling, and natural gas hydrate extraction due to its superior hydraulic performance and erosion capacity. As an intuitive analysis method, image processing is widely used to investigate the characteristics of submerged cavitation jets. However, due to the lack of quantitative evaluation of the cavitation cloud in image processing, it is difficult to establish the relationship between cavitation cloud image and cavitation performance. Therefore, a novel image processing method based on dimensionless grayscale intensity is proposed in this paper. This method was used under different sample spaces to obtain the maximum mass loss of the sample. The results showed that the method could accurately calculate the maximum mass loss of the sample based on the image processing results. When the sample space is 200 images and the working pressure is 20 MPa, the calculation error of the image processing method for the maximum mass loss of the sample is 1.26%. For the sample spaces of 10–5000 images, the maximum calculation error of the image processing method for the maximum mass loss of the samples is 3.29%. The image processing method proposed in this paper establishes the relationship between the cavitation cloud image and the maximum mass loss of the samples, which provides help for further understanding and application of submerged cavitation jets.

Ship fouling not only increases ship resistance and fuel consumption but is equally a type of biological invasion, which causes severe ecological damage. Submerged cavitation jet cleaning is an environmentally friendly, high-efficiency, and energy-saving cleaning method. The nozzle structure has an essential influence on the cleaning effect. Thus, a two-throat nozzle was designed for application in submerged cavitation jet cleaning. To investigate the cavitation characteristics of the two-throat nozzle, a high-speed photographic visualization experiment and an erosion experiment concerning the submerged cavitation jet were carried out in this study. The frame-difference method (FDM) was used to analyze the dynamic changes in the cavitation cloud in a single period. The dynamic changes in the cavitation cloud and the characteristics of the submerged cavitation jet were investigated under different inlet pressures. The sample mass loss and the macroscopic and microscopic changes in surface morphology were used to evaluate the cavitation intensity of the two-throat nozzle submerged jet. The experimental results demonstrate that the two-throat nozzle has a good cavitation effect, and the cavitation cloud of the submerged jet has obvious periodicity. With the increase in inlet pressure, the length, width, and area of the cavitation cloud continue to increase, and the shedding frequency of the cavitation cloud continues to decrease. The intensity of cavitation erosion is related to target distance and impact time. There is an appropriate target distance by which to achieve the optimal cavitation effect. The collapse of cavitation bubbles near the sample surface is related to the erosion distribution on the sample surface. Moreover, the magnitude of the absolute values of the root-mean-square surface roughness and surface skewness increase with cavitation intensity. The results in this paper are helpful for a better understanding of the cavitation characteristics of the two-throat nozzle submerged jet.

Objective To screen the prognostic influencing factors of patients with endovascular treatment for acute basilar artery occlusion (ABAO⁃EVT). Methods The baseline, clinical and follow⁃up data of 215 patients with ABAO⁃EVT from October 2017 to August 2022 in The First Affiliated Hospital of University of Science and Technology of China, Linyi People's Hospital of Shandong and Maoming People's Hospital of Guangdong were retrospectively collected, including sex, age, stroke or transient ischemic attack (TIA), hypertension, diabetes, coronary heart disease, atrial fibrillation, smoking and drinking history, National Institutes of Health Stroke Scale (NIHSS) score, intravenous thrombolysis, first pass effect, times of embolectomy, extended Thrombolysis in Cerebral Infarction (eTICI), and modified Rankin Scale (mRS) score 90 d after operation. According to the 90 d mRS score, the patients were divided into 2 groups: good prognosis group (mRS score 0-3, n = 93) and poor prognosis group (mRS score 4-6, n = 122). Univariate and multivariate stepwise Logistic regression analyses were used to screen the neurological prognostic influencing factors of ABAO ⁃ EVT patients 90 d after operation. Results Logistic regression analysis showed that the baseline NIHSS score increased was a risk factor for poor prognosis of ABAO⁃EVT patients (aOR = 0.936, 95%CI: 0.907-0.965, P = 0.000; aOR = 0.940, 95%CI: 0.910-0.970, P = 0.000), with the first pass effect (aOR = 5.752, 95%CI: 2.875-11.508; P = 0.000), eTICI grade 2c-3 (aOR = 7.113, 95%CI: 3.665-13.805; P = 0.000) were protective factors for good prognosis. Conclusions Low baseline NIHSS score, first pass effect and reperfusion level of eTICI 2c-3 are all protective factors for good neurological prognosis of ABAO⁃EVT patients.

Background It remains unclear whether intensification of the chemotherapy backbone in tandem with an anti-EGFR can confer superior clinical outcomes in a cohort of RAS/BRAF wild-type colorectal cancer (CRC) patients with initially unresectable colorectal liver metastases (CRLM). To that end, we sought to comparatively evaluate the efficacy and safety of cetuximab plus FOLFOXIRI (triplet arm) versus cetuximab plus FOLFOX (doublet arm) as a conversion regimen (i.e., unresectable to resectable) in CRC patients with unresectable CRLM. Methods and findings This open-label, randomized clinical trial was conducted from April 2018 to December 2022 in 7 medical centers across China, enrolling 146 RAS/BRAF wild-type CRC patients with initially unresectable CRLM. A stratified blocked randomization method was utilized to assign patients (1:1) to either the cetuximab plus FOLFOXIRI (n = 72) or cetuximab plus FOLFOX (n = 74) treatment arms. Stratification factors were tumor location (left versus right) and resectability (technically unresectable versus [greater than or equal to]5 metastases). The primary outcome was the objective response rate (ORR). Secondary outcomes included the median depth of tumor response (DpR), early tumor shrinkage (ETS), R0 resection rate, progression-free survival (PFS), overall survival (not mature at the time of analysis), and safety profile. Radiological tumor evaluations were conducted by radiologists blinded to the group allocation. Primary efficacy analyses were conducted based on the intention-to-treat population, while safety analyses were performed on patients who received at least 1 line of chemotherapy. A total of 14 patients (9.6%) were lost to follow-up (9 in the doublet arm and 5 in the triplet arm). The ORR was comparable following adjustment for stratification factors, with 84.7% versus 79.7% in the triplet and doublet arms, respectively (odds ratio [OR] 0.70; 95% confidence intervals [CI] [0.30, 1.67], Chi-square p = 0.42). Moreover, the ETS rate showed no significant difference between the triplet and doublet arms (80.6% (58/72) versus 77.0% (57/74), OR 0.82, 95% CI [0.37, 1.83], Chi-square p = 0.63). Although median DpR was higher in the triplet therapy group (59.6%, interquartile range [IQR], [50.0, 69.7] versus 55.0%, IQR [42.8, 63.8], Mann-Whitney p = 0.039), the R0/R1 resection rate with or without radiofrequency ablation/stereotactic body radiation therapy was comparable with 54.2% (39/72) of patients in the triplet arm versus 52.7% (39/74) in the doublet arm. At a median follow-up of 26.2 months (IQR [12.8, 40.5]), the median PFS was 11.8 months in the triplet arm versus 13.4 months in the doublet arm (hazard ratio [HR] 0.74, 95% CI [0.50, 1.11], Log-rank p = 0.14). Grade [greater than or equal to] 3 events were reported in 47.2% (35/74) of patients in the doublet arm and 55.9% (38/68) of patients in the triplet arm. The triplet arm was associated with a higher incidence of grade [greater than or equal to] 3 neutropenia (44.1% versus 27.0%, p = 0.03) and diarrhea (5.9% versus 0%, p = 0.03). The primary limitations of the study encompass the inherent bias in subjective surgical decisions regarding resection feasibility, as well as the lack of a centralized assessment for ORR and resection. Conclusions The combination of cetuximab with FOLFOXIRI did not significantly improve ORR compared to cetuximab plus FOLFOX. Despite achieving an enhanced DpR, this improvement did not translate into improved R0 resection rates or PFS. Moreover, the triplet arm was associated with an increase in treatment-related toxicity. Trial Registration ClinicalTrials.gov Identifier: NCT03493048., Author(s): De-Shen Wang 1, Chao Ren 1, Shan-Shan Li 2, William Pat Fong 1, Xiao-Jun Wu 3, Jian Xiao 2,4, Bin-Kui Li 5, Yun Zheng 5, Pei-Rong Ding 3, Gong [...]