Ficolin-A induces macrophage polarization to a novel pro-inflammatory phenotype distinct from classical M1.

BACKGROUND: Macrophages are key inflammatory immune cells that orchestrate the initiation and progression of autoimmune diseases. The characters of macrophage in diseases are determined by its phenotype in response to the local microenvironment. Ficolins have been confirmed as crucial contributors to autoimmune diseases, with Ficolin-2 being particularly elevated in patients with autoimmune diseases. However, whether Ficolin-A stimulates macrophage polarization is still poorly understood. METHODS: We investigated the transcriptomic expression profile of murine bone marrow-derived macrophages (BMDMs) stimulated with Ficolin-A using RNA-sequencing. To further confirm a distinct phenotype activated by Ficolin-A, quantitative RT-PCR and Luminex assay were performed in this study. Additionally, we assessed the activation of underlying cell signaling pathways triggered by Ficolin-A. Finally, the impact of Ficolin-A on macrophages were investigated in vivo through building Collagen-induced arthritis (CIA) and Dextran Sulfate Sodium Salt (DSS)-induced colitis mouse models with Fcna-/- mice. RESULTS: Ficolin-A activated macrophages into a pro-inflammatory phenotype distinct to LPS-, IFN-γ- and IFN-γ + LPS-induced phenotypes. The transcriptomic profile induced by Ficolin-A was primarily characterized by upregulation of interleukins, chemokines, iNOS, and Arginase 1, along with downregulation of CD86 and CD206, setting it apart from the M1 and M2 phenotypes. The activation effect of Ficolin-A on macrophages deteriorated the symptoms of CIA and DSS mouse models, and the deletion of Fcna significantly alleviated the severity of diseases in mice. CONCLUSION: Our work used transcriptomic analysis by RNA-Seq to investigate the impact of Ficolin-A on macrophage polarization. Our findings demonstrate that Ficolin-A induces a novel pro-inflammatory phenotype distinct to the phenotypes activated by LPS, IFN-γ and IFN-γ + LPS on macrophages.

Prediction of esophageal cancer risk based on genetic variants and environmental risk factors in Chinese population.

BACKGROUND: Results regarding whether it is essential to incorporate genetic variants into risk prediction models for esophageal cancer (EC) are inconsistent due to the different genetic backgrounds of the populations studied. We aimed to identify single-nucleotide polymorphisms (SNPs) associated with EC among the Chinese population and to evaluate the performance of genetic and non-genetic factors in a risk model for developing EC. METHODS: A meta-analysis was performed to systematically identify potential SNPs, which were further verified by a case-control study. Three risk models were developed: a genetic model with weighted genetic risk score (wGRS) based on promising SNPs, a non-genetic model with environmental risk factors, and a combined model including both genetic and non-genetic factors. The discrimination ability of the models was compared using the area under the receiver operating characteristic curve (AUC) and the net reclassification index (NRI). The Akaike information criterion (AIC) and Bayesian information criterion (BIC) were used to assess the goodness-of-fit of the models. RESULTS: Five promising SNPs were ultimately utilized to calculate the wGRS. Individuals in the highest quartile of the wGRS had a 4.93-fold (95% confidence interval [CI]: 2.59 to 9.38) increased risk of EC compared with those in the lowest quartile. The genetic or non-genetic model identified EC patients with AUCs ranging from 0.618 to 0.650. The combined model had an AUC of 0.707 (95% CI: 0.669 to 0.743) and was the best-fitting model (AIC = 750.55, BIC = 759.34). The NRI improved when the wGRS was added to the risk model with non-genetic factors only (NRI = 0.082, P = 0.037). CONCLUSIONS: Among the three risk models for EC, the combined model showed optimal predictive performance and can help to identify individuals at risk of EC for tailored preventive measures.

Structural basis of TRPV1 modulation by endogenous bioactive lipids.

TRP ion channels are modulated by phosphoinositide lipids, but the underlying structural mechanisms remain unclear. The capsaicin- and heat-activated receptor, TRPV1, has served as a model for deciphering lipid modulation, which is relevant to understanding how pro-algesic agents enhance channel activity in the setting of inflammatory pain. Identification of a pocket within the TRPV1 transmembrane core has provided initial clues as to how phosphoinositide lipids bind to and regulate the channel. Here we show that this regulatory pocket in rat TRPV1 can accommodate diverse lipid species, including the inflammatory lipid lysophosphatidic acid, whose actions are determined by their specific modes of binding. Furthermore, we show that an empty-pocket channel lacking an endogenous phosphoinositide lipid assumes an agonist-like state, even at low temperature, substantiating the concept that phosphoinositide lipids serve as negative TRPV1 modulators whose ejection from the binding pocket is a critical step toward activation by thermal or chemical stimuli.

Near-Infrared Triggered Biodegradable Microneedle Patch for Controlled Macromolecule Drug Release.

Transdermal drug delivery of macromolecule drugs attracts significant attention due to the advantage of convenience and biocompatibility. However, the practical usage of it is limited by the low delivery efficiency and poor drug absorption. To develop an efficient, safe, and controllable transdermal delivery method, the near-infrared (NIR) triggered calcium sulfate and gelatin biodegradable composite microneedle (MN) patches are developed. The MN patches are fabricated by polydimethylsiloxane (PDMS) molds, and the structure data can be adjusted by changing the molds. Such an MN patch can release both macro and micro molecule drugs. After loading with photothermal converter IR780, which can transfer energy of light to heat, the release of macromolecule drugs in MNs can be controlled by applying NIR irradiation. The control effect can be enhanced by spraying 1-tetradecanol (TD) coating and optimizing the ratio (weight) of gelatin and calcium sulfate to 2:6. Besides, the MN patch can deliver drugs through the skin barrier, and the process can be controlled by NIR. Moreover, the insulin-loaded MN patch exhibits some therapeutic effects on healthy mice. This work suggests that biodegradable MNs can achieve controllable drug delivery and potentially be applied in individual treatment via transdermal ingestion.

Structure and function of an intermediate GPCR-Gαßγ complex.

Unraveling the signaling roles of intermediate complexes is pivotal for G protein-coupled receptor (GPCR) drug development. Despite hundreds of GPCR-Gαßγ structures, these snapshots primarily capture the fully activated end-state complex. Consequently, a comprehensive understanding of the conformational transitions during GPCR activation and the roles of intermediate GPCR-G protein complexes in signaling remain elusive. Guided by a conformational landscape profiled by 19 F quantitative NMR ( 19 F-qNMR) and Molecular Dynamics (MD) simulations, we resolved the structure of an unliganded GPCR-G protein intermediate complex by blocking its transition to the fully activated end-state complex. More importantly, we presented direct evidence that the intermediate GPCR-Gαsßγ complex initiates a rate-limited nucleotide exchange without progressing to the fully activated end-state complex, thereby bridging a significant gap in our understanding the complexity of GPCR signaling. Understanding the roles of individual conformational states and their complexes in signaling efficacy and bias will help us to design drugs that discriminately target a disease-related conformation.

Comparing Electrochemical Passivation and Surface Film Chemistry of 654SMO Stainless Steel and C276 Alloy in Simulated Flue Gas Desulfurization Condensates.

This research examines the behavior of electrochemical passivation and the chemistry of surface films on 654SMO super austenitic stainless steel and C276 nickel-based alloy in simulated condensates from flue gas desulfurization in power plant chimneys. The findings indicate that the resistance to polarization of the protective film on both materials initially rises and then falls with either time spent in the solution or the potential of anodic polarization. Comparatively, 654SMO exhibits greater polarization resistance than C276, indicating its potential suitability as a chimney lining material. Mott-Schottky analysis demonstrates that the density of donors in the passive film formed on 654SMO exceeds that on C276, potentially due to the abundance of Fe oxide in the passive film, which exhibits the characteristics of an n-type semiconductor. The primary components of the passive films on both materials are Fe oxides and Cr oxides. The formation of a thin passive film on C276 in the simulated condensates is a result of the low Gibbs free energy of nickel oxide and low Cr content. The slower diffusion coefficient of point defects leads to the development of a thicker and more compact passive film on the surface of 654SMO.

Surgical options and survival prognosis in geriatric patients beyond average lifespan with locally advanced gastric cancer: a propensity score-matched analysis.

BACKGROUND: The appropriateness of laparoscopic gastrectomy (LG) for super-geriatric patients with locally advanced gastric cancer (LAGC) is inconclusive, and the prognostic factors are also yet to be elucidated. Herein, we aimed to investigate the surgical and oncological outcomes of LG versus open gastrectomy (OG) for geriatric patients with LAGC who have outlived the average lifespan of the Chinese population (≥ 78 years). METHODS: This is a monocentric, retrospective, comparative study. A 1:1 propensity score matching (PSM) was performed to minimize selection bias and ensure well-balanced characteristics. The primary endpoint of interest was 3-year overall survival, while secondary endpoints included procedure-related variables, postoperative recovery indices, and complications. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify unfavorable prognostic factors. RESULTS: Of 196 eligible individuals, 107 underwent LG and 89 underwent OG, with a median age (interquartile range [IQR]) of 82 [79, 84] years. PSM yielded 61 matched pairs, with comparable demographic and tumor characteristics. The LG group had a significantly lower overall complication rate than the OG group (31.1% vs. 49.2%, P = 0.042), as well as shorter duration of postoperative hospital stay [12 (11, 13) vs. 13 (12, 15.5) d, P < 0. 001], less intraoperative blood loss [95 (75, 150) vs. 230 (195, 290) mL, P < 0.001], but a longer operative time [228 (210, 255.5) vs. 196 (180, 219.5) min, P < 0.001]. The times to first aerofluxus, defecation, liquid diet, and half-liquid diet were comparable. Kaplan-Meier analyses revealed no significant difference in 3-year overall survival between the groups, either in the entire cohort or in subgroups with different TNM staging. Moreover, Age-adjusted Charlson Comorbidity Index scores of > 6 [hazard ratio (HR) 4.003; P = 0.021] and pathologic TNM stage III (HR 3.816, P = 0.023) were independent unfavorable prognostic factors for long-term survival. CONCLUSIONS: LG performed by experienced surgeons offers the benefits of comparable or better surgical and oncological safety profiles than OG for super-geriatric patients with LAGC.

Deep learning radiomics-based prediction model of metachronous distant metastasis following curative resection for retroperitoneal leiomyosarcoma: a bicentric study.

BACKGROUND: Combining conventional radiomics models with deep learning features can result in superior performance in predicting the prognosis of patients with tumors; however, this approach has never been evaluated for the prediction of metachronous distant metastasis (MDM) among patients with retroperitoneal leiomyosarcoma (RLS). Thus, the purpose of this study was to develop and validate a preoperative contrast-enhanced computed tomography (CECT)-based deep learning radiomics model for predicting the occurrence of MDM in patients with RLS undergoing complete surgical resection. METHODS: A total of 179 patients who had undergone surgery for the treatment of histologically confirmed RLS were retrospectively recruited from two tertiary sarcoma centers. Semantic segmentation features derived from a convolutional neural network deep learning model as well as conventional hand-crafted radiomics features were extracted from preoperative three-phase CECT images to quantify the sarcoma phenotypes. A conventional radiomics signature (RS) and a deep learning radiomics signature (DLRS) that incorporated hand-crafted radiomics and deep learning features were developed to predict the risk of MDM. Additionally, a deep learning radiomics nomogram (DLRN) was established to evaluate the incremental prognostic significance of the DLRS in combination with clinico-radiological predictors. RESULTS: The comparison of the area under the curve (AUC) values in the external validation set, as determined by the DeLong test, demonstrated that the integrated DLRN, DLRS, and RS models all exhibited superior predictive performance compared with that of the clinical model (AUC 0.786 [95% confidence interval 0.649-0.923] vs. 0.822 [0.692-0.952] vs. 0.733 [0.573-0.892] vs. 0.511 [0.359-0.662]; both P < 0.05). The decision curve analyses graphically indicated that utilizing the DLRN for risk stratification provided greater net benefits than those achieved using the DLRS, RS and clinical models. Good alignment with the calibration curve indicated that the DLRN also exhibited good performance. CONCLUSIONS: The novel CECT-based DLRN developed in this study demonstrated promising performance in the preoperative prediction of the risk of MDM following curative resection in patients with RLS. The DLRN, which outperformed the other three models, could provide valuable information for predicting surgical efficacy and tailoring individualized treatment plans in this patient population. TRIAL REGISTRATION: Not applicable.

The composition of Tibetan kefir grain TKG-Y and the antibacterial potential and milk fermentation ability of S. warneri KYS-164 screened from TKG-Y.

This study utilized high-throughput sequencing and SEM observation to elucidate the microbial composition of a Tibetan herder's homemade kefir grain named TKG-Y. Subsequently, S. warneri KYS-164 was isolated from TKG-Y, which can produce mixed protein substances with antibacterial activity, namely bacteriocin-like inhibitory substances (BLIS). BLIS can significantly reduce the growth rate of Escherichia coli 366-a, Staphylococcus aureus CICC 10384 and mixed strains at low concentrations (1 × MIC). The presence of the warnericin-centered gene cluster in KYS-164 may explain the antibacterial properties of the BLIS. Pepsin and an acidic environment can reduce the number of colonies of KYS-164 by 2.5 Log10 CFU mL-1 within 1 h, and reduce the antibacterial activity of BLIS by 21.48%. S. warneri KYS-164 showed no antibiotic resistance and biological toxicity after 80 subcultures, while BLIS produced by 40 generations of the strain retained their inhibitory efficacy against pathogenic bacteria. After 48-hour fermentation of milk with KYS-164, volatile compounds such as aldehydes, phenols, esters, and alcohols, giving it a floral, fruity, milky, oily, and nutty aroma, were released, enriching the sensory characteristics of dairy products. This study not only revealed the bacterial colony composition information of home-made kefir grain TKG-Y but also discovered and proved that S. warneri KYS-164 has the potential to inhibit bacteria and ferment dairy products. This will provide a basis for subsequent applied research on KYS-164.

Serum anti-CFL1, anti-EZR, and anti-CYPA autoantibody as diagnostic markers in ovarian cancer.

The purpose of this study was to identify novel autoantibodies against tumor-associated antigens (TAAs) and explore a diagnostic panel for Ovarian cancer (OC). Enzyme-linked immunosorbent assay was used to detect the expression of five anti-TAA autoantibodies in the discovery (70 OC and 70 normal controls) and validation cohorts (128 OC and 128 normal controls). Machine learning methods were used to construct a diagnostic panel. Serum samples from 81 patients with benign ovarian disease were used to identify the specificity of anti-TAA autoantibodies for OC. In both the discovery and validation cohorts, the expression of anti-CFL1, anti-EZR, anti-CYPA, and anti-PFN1 was higher in patients with OC than that in normal controls. The area under the receiver operating characteristic curve, sensitivity, and specificity of the panel containing anti-CFL1, anti-EZR, and anti-CYPA were 0.762, 55.56%, and 81.31%. The panel identified 53.06%, 53.33%, and 51.11% of CA125 negative, HE4 negative and the Risk of Ovarian Malignancy Algorithm negative OC patients, respectively. The combination of the three anti-TAA autoantibodies can serve as a favorable diagnostic tool for OC and has the potential to be a complementary biomarker for CA125 and HE4 in the diagnosis of ovarian cancer.

Functionalized graphene-oxide grids enable high-resolution cryo-EM structures of the SNF2h-nucleosome complex without crosslinking.

Single-particle cryo-EM is widely used to determine enzyme-nucleosome complex structures. However, cryo-EM sample preparation remains challenging and inconsistent due to complex denaturation at the air-water interface (AWI). Here, to address this issue, we develop graphene-oxide-coated EM grids functionalized with either single-stranded DNA (ssDNA) or thiol-poly(acrylic acid-co-styrene) (TAASTY) co-polymer. These grids protect complexes between the chromatin remodeler SNF2h and nucleosomes from the AWI and facilitate collection of high-quality micrographs of intact SNF2h-nucleosome complexes in the absence of crosslinking. The data yields maps ranging from 2.3 to 3 Å in resolution. 3D variability analysis reveals nucleotide-state linked conformational changes in SNF2h bound to a nucleosome. In addition, the analysis provides structural evidence for asymmetric coordination between two SNF2h protomers acting on the same nucleosome. We envision these grids will enable similar detailed structural analyses for other enzyme-nucleosome complexes and possibly other protein-nucleic acid complexes in general.

Performance of LWIR to VLWIR barrier photodetectors based on M-structure superlattices.

Antimonide superlattice materials with tunable energy bands, high electron mobility, and easy attainment of good uniformity in large-area materials, are considered to be the material of choice for third-generation infrared photodetectors. Based on energy band engineering, this paper designs a series of long-wave infrared(LWIR) to very-long-wave infrared(VLWIR) photodetectors by employing M-structure superlattice(M-SL) as both absorber layer and barrier layer. The photodetectors' performances at different temperatures are simulated in this manuscript. At 77K, while minimizing the lattice mismatch, effectively suppresses the dark current of the device which can be as low as 1× 10-8A/cm2, with a quantum efficiency reaching 20.85% and normalized detectivity achieves 4.78×1011 cm·Hz1/2/W for LWIR photodetector with a cutoff wavelength of 11.1 µm. For the VLWIR photodetector with a cutoff wavelength of 16.7 µm, the corresponding figures are 1×10-6A/cm2, 16.77% and 3.09×1010 cm·Hz1/2/W, respectively.

Renormalized-Residue-Based Multireference Configuration Interaction Method for Strongly Correlated Systems.

The implementation of multireference configuration interaction (MRCI) methods in quantum systems with large active spaces is hindered by the expansion of configuration bases or the intricate handling of reduced density matrices (RDMs). In this work, we present a spin-adapted renormalized-residue-based MRCI (RR-MRCI) approach that leverages renormalized residues to effectively capture the entanglement between active and inactive orbitals. This approach is reinforced by a novel efficient algorithm, which also facilitates an efficient deployment of spin-adapted matrix product state MRCI (MPS-MRCI). The RR-MRCI framework possesses several advantages: (1) It considers the orbital entanglement and utilizes highly compressed MPS structure, improving computational accuracy and efficiency compared with internally contracted (ic) MRCI. (2) Utilizing small-sized buffer environments of a few external orbitals as probes based on quantum information theory, it enhances computational efficiency over MPS-MRCI and offers potential application to large molecular systems. (3) The RR framework can be implemented in conjunction with ic-MRCI, eliminating the need for high-rank RDMs, by using distinct renormalized residues. We evaluated this method across nine diverse molecular systems, including Cu2O22+ with an active space of (24e,24o) and two complexes of lanthanide and actinide with active space (38e,36o), demonstrating the method's versatility and efficacy.

Structural basis of prostaglandin efflux by MRP4.

Multidrug resistance protein 4 (MRP4) is a broadly expressed ATP-binding cassette transporter that is unique among the MRP subfamily for transporting prostanoids, a group of signaling molecules derived from unsaturated fatty acids. To better understand the basis of the substrate selectivity of MRP4, we used cryogenic-electron microscopy to determine six structures of nanodisc-reconstituted MRP4 at various stages throughout its transport cycle. Substrate-bound structures of MRP4 in complex with PGE1, PGE2 and the sulfonated-sterol DHEA-S reveal a common binding site that accommodates a diverse set of organic anions and suggest an allosteric mechanism for substrate-induced enhancement of MRP4 ATPase activity. Our structure of a catalytically compromised MRP4 mutant bound to ATP-Mg2+ is outward-occluded, a conformation previously unobserved in the MRP subfamily and consistent with an alternating-access transport mechanism. Our study provides insights into the endogenous function of this versatile efflux transporter and establishes a basis for MRP4-targeted drug design.

ZPR1 is an immunodiagnostic biomarker and promotes tumor progression in esophageal squamous cell carcinoma.

To evaluate the potential of zinc finger protein 1 (ZPR1) as a diagnostic biomarker and explore the underlying role for esophageal squamous cell carcinoma (ESCC). A human proteome microarray was customized to identify anti-ZPR1 autoantibody, and enzyme-linked immunosorbent assay (ELISA) was adopted to assess the diagnostic performance of anti-ZPR1 autoantibody in 294 patients with ESCC and 294 normal controls. The expression of ZPR1 protein was measured by immunohistochemistry. The effect of ZPR1 on the proliferation, migration, and invasion of ESCC cells was investigated through CCK-8, wound healing, and Transwell assays. The expression level of anti-ZPR1 autoantibody (fold change = 2.77) in ESCC patients was higher than that in normal controls. The receiver operating characteristic (ROC) analysis manifested anti-ZPR1 autoantibody achieved area under the ROC curve (AUC) of 0.726 and 0.734 to distinguish ESCC from normal controls with sensitivity of 50.0% and 42.3%, and specificity of 91.0% and 92.0% in the test group and validation group, respectively. The positive rate of ZPR1 protein was significantly higher in ESCC tissues (75.5%, 80/106) than paracancerous tissues (9.4%, 5/53). Compared with the human normal esophageal cell line, the expression level of ZPR1 mRNA and protein in ESCC lines (KYSE150, Eca109, and TE1) had an increased trend. The knockdown or overexpression of ZPR1 reduced and enhanced the proliferation, migration, and invasion of ESCC cell, respectively. ZPR1 was a potential immunodiagnostic biomarker for noninvasive detection and could be a promotional factor in tumor progression of ESCC.

Biomimetic Wearable Sensors: Emerging Combination of Intelligence and Electronics.

Owing to the advancement of interdisciplinary concepts, for example, wearable electronics, bioelectronics, and intelligent sensing, during the microelectronics industrial revolution, nowadays, extensively mature wearable sensing devices have become new favorites in the noninvasive human healthcare industry. The combination of wearable sensing devices with bionics is driving frontier developments in various fields, such as personalized medical monitoring and flexible electronics, due to the superior biocompatibilities and diverse sensing mechanisms. It is noticed that the integration of desired functions into wearable device materials can be realized by grafting biomimetic intelligence. Therefore, herein, the mechanism by which biomimetic materials satisfy and further enhance system functionality is reviewed. Next, wearable artificial sensory systems that integrate biomimetic sensing into portable sensing devices are introduced, which have received significant attention from the industry owing to their novel sensing approaches and portabilities. To address the limitations encountered by important signal and data units in biomimetic wearable sensing systems, two paths forward are identified and current challenges and opportunities are presented in this field. In summary, this review provides a further comprehensive understanding of the development of biomimetic wearable sensing devices from both breadth and depth perspectives, offering valuable guidance for future research and application expansion of these devices.

How inflammation dictates diabetic peripheral neuropathy: An enlightening review.

BACKGROUND: Diabetic peripheral neuropathy (DPN) constitutes a debilitating complication associated with diabetes. Although, the past decade has seen rapid developments in understanding the complex etiology of DPN, there are no approved therapies that can halt the development of DPN, or target the damaged nerve. Therefore, clarifying the pathogenesis of DPN and finding effective treatment are the crucial issues for the clinical management of DPN. AIMS: This review is aiming to summary the current knowledge on the pathogenesis of DPN, especially the mechanism and application of inflammatory response. METHODS: We systematically summarized the latest studies on the pathogenesis and therapeutic strategies of diabetic neuropathy in PubMed. RESULTS: In this seminal review, the underappreciated role of immune activation in the progression of DPN is scrutinized. Novel insights into the inflammatory regulatory mechanisms of DPN have been unearthed, illuminating potential therapeutic strategies of notable clinical significance. Additionally, a nuanced examination of DPN's complex etiology, including aberrations in glycemic control and insulin signaling pathways, is presented. Crucially, an emphasis has been placed on translating these novel understandings into tangible clinical interventions to ameliorate patient outcomes. CONCLUSIONS: This review is distinguished by synthesizing cutting-edge mechanisms linking inflammation to DPN and identifying innovative, inflammation-targeted therapeutic approaches.

The Potential Predicting Value of D-Dimer to Fibrinogen Ratio on Functional Outcome at 1 Year after Acute Ischemic Stroke: A Longitudinal Study.

INTRODUCTION: Previous studies have suggested that the D-dimer to fibrinogen ratio (DD/Fg) could be a potential predictor for deep vein thrombosis, pulmonary embolism, and stroke severity. However, the association between plasma DD/Fg and functional outcome following acute ischemic stroke (AIS) has been unclear. METHODS: Our study followed the STROBE guideline and used a prospective cohort design to investigate this association. A total of 454 patients with AIS were enrolled consecutively in our study, and the National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) were assessed for stroke severity and functional outcome, respectively. RESULTS: We found a significant difference in DD/Fg values between the three groups based on NIHSS scores at admission. Specifically, the DD/Fg values were higher in the poor functional outcome group (mRS score of 2-6) compared to the favorable functional outcome group (mRS score of 0-1) at the 1-year follow-up (p < 0.001). Additionally, the DD/Fg values were independently associated with poor functional prognosis at 1 year following the onset of stroke, even after adjusting for potential confounders (OR 9.21, 95% CI, 3.68-23.02, p < 0.001). CONCLUSIONS: Our findings suggest that DD/Fg values at admission may serve as risk predictors for poor functional outcomes in patients with AIS 1 year after the stroke.

hccTAAb Atlas: An Integrated Knowledge Database for Tumor-Associated Autoantibodies in Hepatocellular Carcinoma.

Tumor-associated autoantibodies (TAAbs) have demonstrated potential as biomarkers for cancer detection. However, the understanding of their role in hepatocellular carcinoma (HCC) remains limited. In this study, we aimed to systematically collect and standardize information about these TAAbs and establish a comprehensive database as a platform for in-depth research. A total of 170 TAAbs were identified from published papers retrieved from PubMed, Web of Science, and Embase. Following normative reannotation, these TAAbs were referred to as 162 official symbols. The hccTAAb (tumor-associated autoantibodies in hepatocellular carcinoma) atlas was developed using the R Shiny framework and incorporating literature-based and multiomics data sets. This comprehensive online resource provides key information such as sensitivity, specificity, and additional details such as official symbols, official full names, UniProt, NCBI, HPA, neXtProt, and aliases through hyperlinks. Additionally, hccTAAb offers six analytical modules for visualizing expression profiles, survival analysis, immune infiltration, similarity analysis, DNA methylation, and DNA mutation analysis. Overall, the hccTAAb Atlas provides valuable insights into the mechanisms underlying TAAb and has the potential to enhance the diagnosis and treatment of HCC using autoantibodies. The hccTAAb Atlas is freely accessible at https://nscc.v.zzu.edu.cn/hccTAAb/.

Barriers and facilitators of implementing the practice programme for upright positions in the second stage of labour: A mixed-method study.

OBJECTIVE: To explore the possible barriers and facilitators to implementing the Upright Positions in the Second Stage of Labour (UPSSL) programme in Chinese healthcare settings. DESIGN: A mixed-method convergent design with the guidance of Consolidated Framework for Implementation Research (CFIR). METHODS: An online survey study and semi-structured interviews were conducted between March and May 2023. Healthcare professionals were recruited from four hospitals in Shijiazhuang, China. One hundred and thirty-one participants completed the survey study, and 23 of them were interviewed individually. Descriptive statistics evaluated the possible barriers and facilitators of implementing the UPSSL programme within the CFIR framework quantitatively. Guided by the CFIR framework, qualitative data were analysed using directed content analysis to summarize healthcare professionals' perspectives on barriers and facilitators of the UPSSL programme. RESULTS: Multiple intersectional barriers and facilitators were identified from the survey and semi-interviews. Healthcare professionals believed that the UPSSL programme has a scientific evidence base, systematic contents, and possible benefits for women. However, various barriers existed at individual, system, and organizational levels. Major barriers included healthcare professionals and women's safety concerns towards the use of upright positions during childbirth, the healthcare professionals' unfamiliarity with assisting an upright position birth, poor adaptability of the programme protocol, inadequate facilities and staffing, and a lack of readiness to change in the clinical setting. CONCLUSIONS: To facilitate the implementation of the UPSSL programme in China, tailored antenatal education on upright positions, especially addressing safety-related issues, should be provided to pregnant women, their families, or peers to enhance their understanding of and familiarity with such positions. Healthcare professionals should also be offered adequate training opportunities and necessary facilities. Furthermore, national-level policy changes might be required to address midwifery workforce shortages. Additionally, further research is warranted to select, adapt, and test effective implementation strategies for programme adoption. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: What problem did the study address? The adoption of upright positions during the second stage of labour could promote better maternal and neonatal outcomes and a positive childbirth experience. However, the adoption of upright positions during the second stage of labour is suboptimal in healthcare settings in China. Barriers and facilitators of implementing upright positions during childbirth are unclear. What were the main findings? A range of barriers and facilitators within the CFIR framework to promote upright positions during childbirth from healthcare professionals' perspectives were identified, and the major barriers included safety concerns towards and unfamiliarity with an upright position birth, inadequate facilities and staffing, and a lack of readiness to change in the clinical setting. Where and on whom will the research have an impact? This study will enable a better understanding of the barriers and facilitators to promoting upright positions in the second stage of labour in China. The smooth and effective implementation of the UPSSL programme could help to promote better maternal and neonatal outcomes and improve women's childbirth experiences. REPORTING METHOD: The reporting of this study followed the Consolidated Criteria for Reporting Qualitative Research (COREQ) and Good Reporting of A Mixed Methods Study (GRAMMS) guidelines. PATIENT OR PUBLIC CONTRIBUTION: In this study, healthcare professionals were involved in refining the topic guides and survey questions. Additionally, findings from the interviews were returned to them for comments and corrections.