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Abstract Autism Spectrum Disorder (ASD) is a prevalent neurological condition with multiple co-occurring comorbidities that seriously affect mental health. Precisely diagnosis of ASD is crucial to intervention and rehabilitation. A single modality may not fully reflect the complex mechanisms underlying ASD, and combining multiple modalities enables a more comprehensive understanding. Here, we propose, DeepASD, an end-to-end trainable regularized graph learning method for ASD prediction, which incorporates heterogeneous multimodal data and latent inter-patient relationships to better understand the pathogenesis of ASD. DeepASD first learns cross-modal feature representations through a multimodal adversarial-regularized encoder, and then constructs adaptive patient similarity networks by leveraging the representations of each modality. DeepASD exploits inter-patient relationships to boost the ASD diagnosis that is implemented by a classifier compositing of graph neural networks. We apply DeepASD to the benchmarking Autism Brain Imaging Data Exchange (ABIDE) data with four modalities. Experimental results show that the proposed DeepASD outperforms eight state-of-the-art baselines on the benchmarking ABIDE data, showing an improvement of 13.25% in accuracy, 7.69% in AUC-ROC, and 17.10% in specificity. DeepASD holds promise for a more comprehensive insight of the complex mechanisms of ASD, leading to improved diagnosis performance.

Abstract Posttraumatic osteoarthritis (PTOA) is closely related to the inflammatory response caused by mechanical injury and leads to joint degeneration. Herein, we aimed to evaluate the role and underlying mechanism of NUMB in PTOA progression. Anterior cruciate ligament transection (ACLT)-induced rats and interleukin (IL)-1β-treated chondrocytes were used as in vivo and in vitro models of PTOA, respectively. The NUMB overexpression plasmid (pcDNA-NUMB) was administered by intra-articular injection to PTOA model rats, and safranin O-fast green staining, the Osteoarthritis Research Society International (OARSI) scoring system, and HE staining were used to evaluate the severity of cartilage damage. The secretion of inflammatory cytokines (TNF-α, IL-1β, and IL-6) and chondrocyte-specific markers (MMP13 and COL2A1) was detected via ELISA. Cell viability and apoptosis were evaluated by MTT and TUNEL assays. NUMB was expressed at lower levels in ACLT-induced PTOA rats and in IL-1β-treated chondrocytes than in control rats and cells. NUMB overexpression enhanced cell viability and reduced cell apoptosis, inflammation and cartilage degradation in chondrocytes stimulated by IL-1β. NUMB bound to BTRC to promote p-IκBα expression, resulting in NF-κB pathway inactivation. BTRC overexpression reversed the promoting effect of NUMB overexpression on cell viability and the inhibitory effects of NUMB overexpression on apoptosis, inflammation and cartilage degradation in IL-1β-induced chondrocytes. In addition, overexpression of NUMB alleviated articular cartilage damage by repressing inflammation and cartilage degradation in ACLT-induced PTOA rats. Our data indicated that NUMB regulated PTOA progression through the BTRC/NF-κB pathway, which may be a viable therapeutic target in PTOA.

Abstract Aim This study aims to explore the duration and influencing factors of care‐seeking delay among patients with heart failure (HF) in China. Methods and results A convergent mixed method containing a cross‐sectional study and two parts of qualitative studies was designed, following the STROBE and COREQ guidelines. Convenience sampling was applied to recruit patients with HF from two general hospitals from December 2021 to December 2022. Purposive sampling was used to enrol healthcare professionals from two general hospitals and two community hospitals from June to November 2022. Among the 258 patients with HF in the cross‐sectional study, the median duration of care‐seeking delay was 7.5 days. The result integration indicated that the delay duration was influenced by the dyspnoea symptom burden, the oedema symptom burden, and the depression status. The lower dyspnoea symptom burden, the higher oedema symptom burden, and the higher depression score were related to the prolonged care‐seeking delay duration. The duration was also affected by the COVID‐19 pandemic, level of support from medical system, and the symptom management abilities of the caregivers. The COVID‐19 pandemic, low level of support from medical system, and limited symptom management abilities of caregivers were related to the prolonged care‐seeking delay duration. Conclusions Care‐seeking delay among patients with HF needs attention in China. The duration of care‐seeking delay of patients with HF was influenced by the dyspnoea symptom burden, the oedema symptom burden, and depression status, as well as the COVID‐19 pandemic, level of support from medical system, and the symptom management abilities of the caregivers.

Abstract Background Clinicians traditionally aim to identify a singular explanation for the clinical presentation of a patient; however, in some cases, the diagnosis may remain elusive or fail to comprehensively explain the clinical findings. In recent years, advancements in next-generation sequencing, including whole-exome sequencing, have led to the incidental identification of dual diagnoses in patients. Herein we present the cases of five pediatric patients diagnosed with dual rare genetic diseases. Their natural history and diagnostic process were explored, and lessons learned from utilizing next-generation diagnostic technologies have been reported. Results Five pediatric cases (3 boys, 2 girls) with dual diagnoses were reported. The age at diagnosis was from 3 months to 10 years. The main clinical presentations were psychomotor retardation and increased muscular tension, some accompanied with liver dysfunction, abnormal appearance, precocious puberty, dorsiflexion restriction and varus of both feet, etc. After whole-exome sequencing, nine diseases were confirmed in these patients: Angelman syndrome and Krabbe disease in case 1, Citrin deficiency and Kabuki syndrome in case 2, Homocysteinemia type 2 and Copy number variant in case 3, Isolated methylmalonic acidemia and Niemann-Pick disease type B in case 4, Isolated methylmalonic acidemia and 21-hydroxylase deficiency in case 5. Fifteen gene mutations and 2 CNVs were identified. Four novel mutations were observed, including c.15292de1A in KMT2D, c.159_164inv and c.1427G > A in SLC25A13, and c.591 C > G in MTHFR. Conclusions Our findings underscore the importance of clinicians being vigilant about the significance of historical and physical examination. Comprehensive clinical experience is crucial for identifying atypical clinical features, particularly in cases involving dual rare genetic diseases.

Abstract Aims We aim to develop and validate a questionnaire on the behaviour of self‐volume management of patients with chronic heart failure. Methods and results Based on the specific situation theory of heart failure self‐care, the items of this questionnaire were formed through literature review and expert consultation. Content validity is judged by expert consultation. Item analysis was used for further filter entries. Cronbach's alpha and retest were used for reliability. Exploratory factor analysis and confirmatory factor analysis were used to test the structural validity. The questionnaire finally contained 3 subscales and 22 items. The Cronbach's α was between 0.732 and 0.797. The reliability of the retest was between 0.983 and 0.998. In expert consultation, the I‐CVI of each item was 0.92–1, and the S‐CVI of each subscale was 0.99, 1.00, and 0.99. In exploratory factor analysis, each subscale has two factors. In confirmatory factor analysis, the model fits of the three subscales were good: χ2/df 0.9, TLI > 0.9, and SRMR

BackgroundSulfasalazine is a widely used anti-inflammatory medication for treating autoimmune disorders such as ulcerative colitis (UC), Crohn’s disease, and rheumatoid arthritis. However, its safety profile has not been systematically evaluated in real-world settings. By analyzing the FDA Adverse Event Reporting System (FAERS) database, we identified risk signals associated with adverse reactions to sulfasalazine, offering valuable insights for clinical decision-making and risk management.MethodsReports of adverse events (AEs) associated with sulfasalazine, covering the period from Q1 2004 to Q4 2023, were extracted from the FAERS database. Detailed case information was aggregated to assess demographic characteristics. The associations between sulfasalazine and adverse events were evaluated using the Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayes Geometric Mean (EBGM).ResultsWe extracted 7,156 adverse event reports from the FAERS database where sulfasalazine was identified as the “Primary Suspect (PS)” drug. Using disproportionality analysis, we identified 101 preferred terms (PT) related to sulfasalazine across 24 organ systems. Notable adverse reactions consistent with the drug’s labeling were observed, including Stevens-Johnson syndrome, agranulocytosis, eosinophilic pneumonia, and crystalluria. Additionally, novel positive signals not previously documented in the drug label were identified, including acute febrile neutrophilic dermatosis, aseptic meningitis, glomerulonephritis, and hepatosplenic T-cell lymphoma.ConclusionMost of the adverse reaction findings in this study are consistent with previous clinical research, and we have also identified new potential AEs associated with sulfasalazine. These findings provide valuable insights for the safety monitoring and clinical application of sulfasalazine.

Many autologous melanocytes are required for surgical treatment of depigmentation diseases such as vitiligo. However, primary cultured melanocytes have a limited number of in vitro passages. The production of functional epidermal melanocytes from stem cells provides an unprecedented source of cell therapy for vitiligo. This study explores the clinical application of melanocytes induced by hair follicle neural crest stem cells (HFNCSCs). This study established an in vitro differentiation model of HFNCSCs into melanocytes. Results demonstrate that most differentiated melanocytes expressed the proteins C-KIT, MITF, S–100B, TYRP1, TYRP2, and tyrosinase. The HFNCSC-derived melanocytes were successfully transplanted onto the dorsal skin of mice and survived in the local tissues, expressing marker protein of melanocytes. In conclusion, HFNCSCs in mice can be induced to differentiate into melanocytes under specific conditions. These induced melanocytes exhibit the potential to facilitate repigmentation in the lesion areas of vitiligo-affected mice, suggesting a promising avenue for therapeutic intervention.

Abstract Commencing with the breakdown of the diabetic osteoimmune microenvironment, multiple pathogenic factors, including hyperglycemia, inflammation, hypoxia, and deleterious cytokines, are conjointly involved in the progression of diabetic periodontal bone regeneration. Based on the challenge of periodontal bone regeneration treatment and the absence of real‐time feedback of blood oxygen fluctuation in diabetes mellitus, a novel self‐adaptive hyperthermia supramolecular cascade nano‐reactor ACFDG is constructed via one‐step supramolecular self‐assembly strategy to address multiple factors in diabetic periodontal bone regeneration. Hyperthermia supramolecular ACFDG possesses high photothermal conversion efficiency (32.1%), and it can effectively inhibit the vicious cycle of ROS‐inflammatory cascade through catalytic cascade reactions, up‐regulate the expression of heat shock proteins (HSPs) under near‐infrared (NIR) irradiation, which promotes periodontal bone regeneration. Remarkably, ACFDG can provide real‐time non‐invasive diagnosis of blood oxygen changes during periodontal bone regeneration through photoacoustic (PA) imaging, thus can timely monitor periodontal hypoxia status. In conclusion, this multifunctional supramolecular nano‐reactor combined with PA imaging for real‐time efficacy monitoring provides important insights into the biological mechanisms of diabetic periodontal bone regeneration and potential clinical theranostics.

Changes in keratin gene expression and spatiotemporal regulation determine the compositional content and cellular localization of wool keratin, thereby affecting wool traits. Therefore, keratin gene family member 32 (KRT32) was selected for a study using RT-qPCR, immunofluorescence, and penta-primer amplification refractory mutation system (PARMS) techniques. The results showed that KRT32 mRNA was highly expressed in the skin and localized to the inner root sheath (IRS), outer root sheath (ORS) and dermal papilla (DP). Sequencing results identified eight SNPs in KRT32, and association analyses revealed that the variations were significantly associated with multiple traits in wool (p < 0.05), including MFD, CF and MFC. The constructed haplotype combination H2H3 has higher CF and smaller MFD than other haplotype combination (p < 0.05). In conclusion, KRT32 can be used as a candidate gene for molecular genetic improvement of wool in Gansu Alpine Fine-wool sheep.

Abstract Objective Idiopathic infantile hypercalcemia (IIH) is a rare disorder of PTH-independent hypercalcemia. CYP24A1 and SLC34A1 gene mutations cause two forms of hereditary IIH. In this study, the clinical manifestations and molecular aspects of six new Chinese patients were investigated. Methods The clinical manifestations and laboratory study of six patients with idiopathic infantile hypercalcemia were analyzed retrospectively. Results Five of the patients were diagnosed with hypercalcemia, hypercalciuria, and bilateral medullary nephrocalcinosis. Their clinical symptoms and biochemical abnormalities improved after treatment. One patient presented at age 11 years old with arterial hypertension, hypercalciuria and nephrocalcinosis, but normal serum calcium. Gene analysis showed that two patients had compound heterozygous mutations of CYP24A1, one patient had a monoallelic CYP24A1 variant, and three patients had a monoallelic SLC34A1 variant. Four novel CYP24A1 variants (c.116G > C, c.287T > A, c.476G > A and c.1349T > C) and three novel SLC34A1 variants (c.1322 A > G, c.1697_1698insT and c.1726T > C) were found in these patients. Conclusions A monoallelic variant of CYP24A1 or SLC34A1 gene contributes to symptomatic hypercalcemia, hypercalciuria and nephrocalcinosis. Manifestations of IIH vary with onset age. Hypercalcemia may not necessarily present after infancy and IIH should be considered in patients with nephrolithiasis either in older children or adults.

Abstract Background The pathogenesis of vitiligo remains unclear. The genes encoding vitiligo-related RNA-binding proteins (RBPs) and their underlying pathogenic mechanism have not been determined. Results Single-cell transcriptome sequencing (scRNA-seq) data from the CNCB database was obtained to identify distinct cell types and subpopulations and the relative proportion changes in vitiligo and healthy samples. We identified 14 different cell types and 28 cell subpopulations. The proportion of each cell subpopulation significantly differed between the patients with vitiligo and healthy groups. Using RBP genes for unsupervised clustering, we obtained the specific RBP genes of different cell types in vitiligo and healthy groups. The RBP gene expression was highly heterogeneous; there were significant differences in some cell types, such as keratinocytes, Langerhans, and melanocytes, while there were no significant differences in other cells, such as T cells and fibroblasts, in the two groups. The melanocyte-specific RBP genes were enriched in the apoptosis and immune-related pathways in the patients with vitiligo. Combined with the bulk RNA-seq data of melanocytes, key RBP genes related to melanocytes were identified, including eight upregulated RBP genes (CDKN2A, HLA-A, RPL12, RPL29, RPL31, RPS19, RPS21, and RPS28) and one downregulated RBP gene (SLC3A2). Cell experiments were conducted to explore the role of the key RBP gene SLC3A2 in vitiligo. Cell experiments confirmed that melanocyte proliferation decreased, whereas apoptosis increased, after SLC3A2 knockdown. SLC3A2 knockdown in melanocytes also decreased the SOD activity and melanin content; increased the Fe2+, ROS, and MDA content; significantly increased the expression levels of TYR and COX2; and decreased the expression levels of glutathione and GPX4. Conclusion We identified the RBP genes of different cell subsets in patients with vitiligo and confirmed that downregulating SLC3A2 can promote ferroptosis in melanocytes. These findings provide new insights into the pathogenesis of vitiligo.

Chimeric antigen receptor T cell denoted as CAR-T therapy has realized incredible therapeutic advancements for B cell malignancy treatment. However, its therapeutic validity has yet to be successfully achieved in solid tumors. Different from hematological cancers, solid tumors are characterized by dysregulated blood vessels, dense extracellular matrix, and filled with immunosuppressive signals, which together result in CAR-T cells’ insufficient infiltration and rapid dysfunction. The insufficient recognition of tumor cells and tumor heterogeneity eventually causes cancer reoccurrences. In addition, CAR-T therapy also raises safety concerns, including potential cytokine release storm, on-target/off-tumor toxicities, and neuro-system side effects. Here we comprehensively review various targeting aspects, including CAR-T cell design, tumor modulation, and delivery strategy. We believe it is essential to rationally design a combinatory CAR-T therapy via constructing optimized CAR-T cells, directly manipulating tumor tissue microenvironments, and selecting the most suitable delivery strategy to achieve the optimal outcome in both safety and efficacy.

Abstract This work aims to investigate how smoking exerts effect on the development of inflammatory bowel disease (IBD). A prospective cohort study and a Mendelian randomization study are first conducted to evaluate the association between smoking behaviors, smoking-related DNA methylation and the risks of Crohn’s disease (CD) and ulcerative colitis (UC). We then perform both genome-wide methylation analysis and co-localization analysis to validate the observed associations. Compared to never smoking, current and previous smoking habits are associated with increased CD (P = 7.09 × 10−10) and UC (P

Abstract Background Diabetic nephropathy (DN) is a diabetic complication. LncRNAs are reported to participate in the pathophysiology of DN. Here, the function and mechanism of lncRNA small nucleolar RNA host gene 14 (SNHG14) in DN were explored. Methods Streptozotocin (STZ)‐induced DN mouse models and high glucose (HG)‐treated human mesangial cells (MCs) were used to detect SNHG14 expression. SNHG14 silencing plasmids were applied to examine the function of SNHG14 on proliferation and fibrosis in HG‐treated MCs. Potential targets of SNHG14 were predicted using bioinformatics tools and verified by luciferase reporter, RNA pulldown, and northern blotting assays. The functional role of SNHG14 in DN in vivo was detected by injection with adenoviral vector carrying sh‐SNHG14 into DN mice. Serum creatinine, blood urea nitrogen, blood glucose, 24‐h proteinuria, relative kidney weight, and renal pathological changes were examined in DN mice. Results SNHG14 expression was elevated in the kidneys of DN mice and HG‐treated MCs. SNHG14 silencing inhibited proliferation and fibrosis of HG‐stimulated MCs. SNHG14 bound to miR‐30e‐5p to upregulate SOX4 expression. In rescue assays, SOX4 elevation diminished the effects of SNHG14 silencing in HG‐treated MCs, and SOX4 silencing reversed the effects of SNHG14 overexpression. In in vivo studies, SNHG14 downregulation significantly ameliorated renal injuries and renal interstitial fibrosis in DN mice. Conclusions SNHG14 silencing attenuates kidney injury in DN mice and reduces proliferation and fibrotic phenotype of HG‐stimulated MCs via the miR‐30e‐5p/SOX4 axis.

Summary: Large prospective studies are required to better elucidate the associations of physical activity, sedentary behaviors (SBs), and sleep with overall cancer and site-specific cancer risk, accounting for the interactions with genetic predisposition. The study included 360,271 individuals in UK Biobank. After a median follow-up of 12.52 years, we found higher total physical activity (TPA) level and higher sleep scores were related to reduced risk of cancer while higher SB level showed a positive association with cancer. Compared with high TPA-healthy sleep group and low SB-healthy sleep group, low TPA-poor sleep group and high SB-poor sleep group had the highest risk for overall cancer, breast cancer, and lung cancer. Adherence to a more active exercise pattern was associated with a lower risk of cancer irrespective of genetic risk. Our study suggests that improving the quality of sleep and developing physical activity habits might yield benefits in mitigating the cancer risk.

Abstract Insufficient tumor immunogenicity and immune escape from tumors remain common problems in all tumor immunotherapies. Recent studies have shown that pyroptosis, a form of programmed cell death that is accompanied by immune checkpoint inhibitors, can induce effective immunogenic cell death and long‐term immune activation. Therapeutic strategies to jointly induce pyroptosis and reverse immunosuppressive tumor microenvironments are promising for cancer immunotherapy. In this regard, a dual‐responsive supramolecular polymeric nanomedicine (NCSNPs) to self‐cascade amplify the benefits of cancer immunotherapy is designed. The NCSNPs are formulated by β‐cyclodextrin coupling nitric oxide (NO) donor, a pyroptosis activator, and NLG919, an indoleamine 2,3‐dioxygenase (IDO) inhibitor, and self‐assembled through host–guest molecular recognition and hydrophobic interaction to obtain nanoparticles. NCSNPs possess excellent tumor accumulation and bioavailability attributed to ingenious supramolecular engineering. The study not only confirms the occurrence of NO‐triggered pyroptosis in tumors for the first time but also reverses the immunosuppressive microenvironment in tumor sites via an IDO inhibitor by enhancing the infiltration of cytotoxic T lymphocytes, to achieve remarkable inhibition of tumor proliferation. Thus, this study provides a novel strategy for cancer immunotherapy.

In this study, a two-dimensional Ti3C2Tx MXene compounded with carbon nanohorn (CNH) by an electrostatic self-assembly method was proposed and then fabricated as room temperature ammonia (NH3) gas sensors. The successful preparation of the Ti3C2Tx/CNH nanocomposite has been characterized in detail. The NH3 sensing performance based on Ti3C2Tx/CNH also has been tested at room temperature. The optimal Ti3C2Tx/CNH sensor has a response value of 21.6% to 100 ppm NH3 at room temperature, which is 10 times higher than that of the pure Ti3C2Tx sensor. Furthermore, this sensor is endowed with excellent selectivity, reliable long-term stability, and reproducibility. The enhanced sensing performance is associated with the interconnected structure and the synergistic effect of Ti3C2Tx and CNH. This work provides an effective way to prepare MXene-based sensitive materials for NH3 sensors, which shows excellent NH3 detection potential at room temperature.

This paper discusses the significance of pipeline gas drainage tester for coal mine safety production, analyzes the problems existing in the use of similar products in coal mines. In accordance with the provisions of article 47 of the Detailed Rules for the Prevention and Control of Coal and Gas Outburst on drill hole measurement in pre-drainage coal seams, we have developed a portable multi-parameter measuring instrument for gas drainage pipelines from three aspects: process technology, optimization algorithm and internal structure. This article provides a detailed introduction to the design scheme of the measuring instrument from key hardware aspects such as overall scheme and performance indicators, power supply and storage, as well as key software aspects such as data reception, storage protection, and flow calculation. Through extensive on-site testing and certification, the measuring instrument has solved the problems of “slow measurement, inaccurate measurement, and heavy instrument” in the concentration and negative pressure of the pumping borehole, ensuring that the staff master the accuracy of the pre pumping borehole parameters.

Objectives: This study aimed to review and summarize the studies of nurse-coordinated home-based cardiac rehabilitation for patients with heart failure. Methods: The review was performed using Arksey and O’Malley’s scoping review framework. A systematic search was conducted across eight databases, including PubMed, Embase, Web of Science, EBSCO, China Biomedical Literature Service System (SinoMed), China National Knowledge Infrastructure (CNKI), Wanfang Database, and Chinese Science and Technology Journals (CSTJ) Database, and Chinese Clinical Trial Registry, from inception to 30 April 2023. Articles relevant to the nurse-coordinated home-based cardiac rehabilitation for patients with heart failure were included. Results: Eighteen studies were included in this review. These studies showed that nurses primarily focused on patient assessment, home-based cardiac rehabilitation planning and guidance, and follow-up. The studies also reported positive outcomes in patient safety, feasibility, and efficacy of the programs coordinated by nurses. Conclusions: Home-based cardiac rehabilitation coordinated by nurses is beneficial to patients with heart failure. Future research will explore the potential of nurses in home-based cardiac rehabilitation for patients with heart failure, determine optimal evaluation criteria, and formulate safe, effective, and economical rehabilitation programs suitable for the patients.

Abstract Backscatter communication (BackCom), the underlying technology for modern‐day Radio Frequency Identification, has been studied as a promising solution for future ultra‐low power Internet‐of‐Things (IoT) applications. Its development has pushed the performance boundaries significantly, in terms of communication distance, data transmission rate, and power consumption. An up‐to‐date review of one branch of BackCom systems, namely Ambient BackCom, which utilises the already available ambient signals, instead of a dedicated radio frequency carrier in most of the BackCom works, to establish BackCom links is conducted. This further reduces the cost and complexity of the system and opens an opportunity for mass deployment.

The toxicity of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is generally believed to be mediated by aryl hydrocarbon receptor (AhR), but some evidence suggests that the effects of TCDD can also be produced through AhR-independent mechanisms. In previous experiments, we found that mainly AhR-dependent mechanism was involved in the migration inhibition of glioblastoma U87 cells by TCDD. Due to the heterogeneity of glioblastomas, not all tumor cells have significant AhR expression. The effects and mechanisms of TCDD on the migration of glioblastomas with low AhR expression are still unclear. We employed a glioblastoma cell line A172 with low AhR expression as a model, using wound healing and Transwell® assay to detect the effect of TCDD on cell migration. We found that TCDD can inhibit the migration of A172 cells without activating AhR signaling pathway. Further, after being pre-treated with AhR antagonist CH223191, the inhibition of TCDD on A172 cells migration was not changed, indicating that the effect of TCDD on A172 cells is not dependent on AhR activation. By transcriptome sequencing analysis, we propose dysregulation of the expression of certain migration-related genes, such as IL6, IL1B, CXCL8, FOS, SYK, and PTGS2 involved in cytokines, MAPK, NF-κB, and IL-17 signaling pathways, as potential AhR-independent mechanisms that mediate the inhibition of TCDD migration in A172 cells.

Abstract Achieving hemostasis effectively is essential for surgical success and excellent patient outcomes. However, it is challenging to develop hemostatic adhesives that are fast‐acting, strongly adherent, long‐lasting, and biocompatible for treating hemorrhage. In this study, a sequential crosslinking fibrin glue (SCFG) is developed, of which the first network of the fibrin glue forms in situ within 2 s to act as an initial physical barrier and locks the gelatin methacryloyl precursor for tight construction of the second network to enhance wet adhesion and durability for tissues covered with blood. The sequential crosslinking glue can provide large pressures (≈280 mmHg of burst pressure), makes strong (38 kPa of shear strength) and tough (≈60 J m−2 of interfacial toughness) interfaces with wet tissues, and outperforms commercial hemostatic agents and gelatin methacryloyl. SCFG are demonstrated as an effective and safe sealant to enhance the treatment outcomes of bleeding tissues in rat, rabbit, and pig models. The ultrafast gelation, strong adhesion and durability, excellent compatibility, and easy manufacture of SCFG make it a promising hemostatic adhesive for clinical applications.

Introduction The widespread popularity of e-cigarettes is considered an important public health concern. However, only some studies have investigated the prevalence of e-cigarette use in Shanghai, China. Research on the perceived harmfulness of e-cigarettes and public support for e-cigarette regulations in China is limited. This study aimed to estimate e-cigarette awareness, prevalence, and associated factors among adults in Shanghai, China. Methods This study used data from a representative survey conducted in Shanghai, China, in 2019. The survey was conducted at 64 surveillance points in Shanghai, China, using a multistage, stratified, cluster-randomized sampling design, recruiting community-based Chinese adults aged ≥15 years. Based on the principles outlined in the Global Adult Tobacco Survey (GATS) China Project, data were collected by conducting face-to-face interviews in households. Of the 3200 selected households, 3060 people completed the individual survey. The overall response rate was 97.4%. Results In all, 72.3% of the respondents had heard of e-cigarettes. The respondents who had used e-cigarettes at some point in their life, used them in the last 12 months, and used them currently were 5.8%, 2.6%, and 1.3%, respectively. Among adult residents who had heard of e-cigarettes, 38.2% thought they were less harmful than traditional cigarettes. The respondents who perceived e-cigarettes as more harmful than traditional cigarettes were less likely to have ever used e-cigarettes (AOR=0.2; 95% CI: 0.1–0.5, p=0.0015) and more likely to support incorporating e-cigarettes into the regulation of smoking control (AOR=3.9; 95% CI: 1.8–8.6, p=0.0008). Conclusions Our findings reveal that the awareness about e-cigarettes was high, and the prevalence of e-cigarette use was similar to the findings from previous studies in China. The harmful perception of e-cigarettes warrants further attention from public health practitioners.

The sideroflexin (SFXN) family is a group of mitochondrial membrane proteins. Although the function of the SFXN family in mitochondria has been widely recognized, the expression levels, role, and prognostic value of this family in breast cancer (BC) have not been clearly articulated and systematically analysed. In our research, SFXN1 and SFXN2 were significantly upregulated in BC versus normal samples based on Gene Expression Profiling Interactive Analysis 2 and the Human Protein Atlas databases. We found that high SFXN1 expression was significantly related to poor prognosis in BC patients and that high SFXN2 expression was significantly associated with good prognosis in BC patients. Gene Ontology analysis of the SFXN family was performed based on the STRING database to explore the potential functions of this family, including biological processes, cellular components, and molecular functions. Based on the MethSurv database, we found that two SFXN1 CpG sites (5′-UTR-S_Shelf-cg06573254 and TSS200-Island-cg17647431), two SFXN2 CpG sites (3′-UTR-Open_Sea-cg04774043 and Body-Open_Sea-cg18994254), one SFXN3 CpG site (Body-S_Shelf-cg17858697), and nine SFXN5 CpG sites (1stExon;5′-UTR-Island-cg03856450, Body-Open_Sea-cg04016113, Body-Open_Sea-cg04197631, Body-Open_Sea-cg07558704, Body-Open_Sea-cg08383863, Body-Open_Sea-cg10040131, Body-Open_Sea-cg10588340, Body-Open_Sea-cg17046766, and Body-Open_Sea-cg22830638) were significantly related to the prognosis of BC patients. According to the ENCORI database, four negative regulatory miRNAs for SFXN1 (hsa-miR-22-3p, hsa-miR-140-5p, hsa-miR-532-5p, and hsa-miR-582-3p) and four negative regulatory miRNAs for SFXN2 (hsa-miR-9-5p, hsa-miR-34a-5p, hsa-miR-532-5p, and hsa-miR-885-5p) were related to poor prognosis for BC patients. This study suggests that SFXN1 and SFXN2 are valuable biomarkers and treatment targets for patients with BC.

ABSTRACTBreakthrough infections by SARS-CoV-2 variants pose a global challenge to COVID-19 pandemic control, and the development of more effective vaccines of broad-spectrum protection is needed. In this study, we constructed pVAX1-based plasmids encoding receptor-binding domain (RBD) chimera of SARS-CoV-1 and SARS-CoV-2 variants, including pAD1002 (encoding RBDSARS/BA1), pAD1003 (encoding RBDSARS/Beta) and pAD131 (encoding RBDBA1/Beta). Plasmids pAD1002 and pAD131 were far more immunogenic than pAD1003 in terms of eliciting RBD-specific IgG when intramuscularly administered without electroporation. Furthermore, dissolvable microneedle array patches (MAP) greatly enhanced the immunogenicity of these DNA constructs in mice and rabbits. MAP laden with pAD1002 (MAP-1002) significantly outperformed inactivated SARS-CoV-2 virus vaccine in inducing RBD-specific IFN-γ+ effector and memory T cells, and generated T lymphocytes of different homing patterns compared to that induced by electroporated DNA in mice. In consistence with the high titer neutralization results of MAP-1002 antisera against SARS-CoV-2 pseudoviruses, MAP-1002 protected human ACE2-transgenic mice from Omicron BA.1 challenge. Collectively, MAP-based DNA constructs encoding chimeric RBDs of SARS-CoV-1 and SARS-CoV-2 variants, as represented by MAP-1002, are potential COVID-19 vaccine candidates worthy further translational study.

Summary: Accurate detection of liver lesions from multi-phase contrast-enhanced CT (CECT) scans is a fundamental step for precise liver diagnosis and treatment. However, the analysis of multi-phase contexts is heavily challenged by the misalignment caused by respiration coupled with the movement of organs. Here, we proposed an AI system for multi-phase liver lesion segmentation (named MULLET) for precise and fully automatic segmentation of real-patient CECT images. MULLET enables effectively embedding the important ROIs of CECT images and exploring multi-phase contexts by introducing a transformer-based attention mechanism. Evaluated on 1,229 CECT scans from 1,197 patients, MULLET demonstrated significant performance gains in terms of Dice, Recall, and F2 score, which are 5.80%, 6.57%, and 5.87% higher than state of the arts, respectively. MULLET has been successfully deployed in real-world settings. The deployed AI web server provides a powerful system to boost clinical workflows of liver lesion diagnosis and could be straightforwardly extended to general CECT analyses.

Abstract Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) are prevalent critical illnesses with a high mortality rate among patients in intensive care units. Neutrophil extracellular traps (NETs) are implicated in the pathogenesis of ALI/ARDS and represent a promising therapeutic target. However, the clinical application of deoxyribonuclease I (DNase I), the only drug currently available to clear NETs, is limited due to the lack of precise and efficient delivery strategies. Therefore, targeted delivery of DNase I to the inflamed lung remains a critical issue to be addressed. Herein, a novel biomimetic DNase I delivery system is developed (DCNV) that employs genetically and bioorthogonally engineered cellular nanovesicles for pulmonary NETs clearance. The CXC motif chemokine receptor 2 overexpressed cellular nanovesicles can mimic the inflammatory chemotaxis of neutrophils in ALI/ARDS, leading to enhanced lung accumulation. Furthermore, DNase I immobilized through bioorthogonal chemistry exhibits remarkable enzymatic activity in NETs degradation, thus restraining inflammation and safeguarding lung tissue in the lipopolysaccharide‐induced ALI murine model. Collectively, the findings present a groundbreaking proof‐of‐concept in the utilization of biomimetic cellular nanovesicles to deliver DNase I for treating ALI/ARDS. This innovative strategy may usher in a new era in the development of pharmacological interventions for various inflammation‐related diseases.

Abstract Aryl hydrocarbon receptor (AHR) is a ligand-dependent transcriptional factor widely expressed among immune, epithelial, endothelial and stromal cells in barrier tissues. It can be activated by small molecules provided by pollutants, microorganisms, food, and metabolism. It has been demonstrated that AHR plays an important role in modulating the response to many microbial pathogens, and the abnormal expression of AHR signaling pathways may disrupt endocrine, cause immunotoxicity, and even lead to the occurrence of cancer. Most humans are infected with at least one known human cancer virus. While the initial infection with these viruses does not cause major disease, the metabolic activity of infected cells changes, thus affecting the activation of oncogenic signaling pathways. In the past few years, lots of studies have shown that viral infections can affect disease progression by regulating the transmission of multiple signaling pathways. This review aims to discuss the potential effects of virus infections on AHR signaling pathways so that we may find a new strategy to minimize the adverse effects of the AHR pathway on diseases. Video Abstract

The subarray-level multibeam structure is advantageous for minimizing system complexity and enhancing multi-target detection and estimation performance. Furthermore, the subarray configuration plays a major role in determining the multibeam antenna pattern parameters. Therefore, we propose a subarray partition technique based on the tournament algorithm to enable spatial multibeam synthesis. In this paper, subarray configuration and excitation are alternately optimized through multiple rounds of tournament iterations. Each iteration calculates subarray excitations using convex optimization methods to fulfill requirements for the main radiation direction and low sidelobes, among other performance criteria. At the same time, excitations for each unassigned array element are calculated within each subarray separately. Simulation results for linear arrays demonstrate the proposed algorithm is not only suitable for linear arrays but also applicable to other array configurations, such as circular ring arrays and cylindrical arrays. And the proposed algorithm is effective in subarray periodicity, suppressing sidelobe levels, and allocating resources based on priority.

Existing methods for restoring color-distorted images in specific environments typically focus on a singular type of distortion, making it challenging to generalize their application across various types of color-distorted images. If it were possible to leverage the intrinsic connections between different types of color-distorted images and coordinate their interactions during model training, it would simultaneously enhance generalization, address potential overfitting and underfitting issues during data fitting, and consequently lead to a positive performance boost. In this paper, our approach primarily addresses three distinct types of color-distorted images, namely dust-laden images, hazy images, and underwater images. By thoroughly exploiting the unique characteristics and interrelationships of these types, we achieve the objective of multitask processing. Within this endeavor, identifying appropriate correlations is pivotal. To this end, we propose a knowledge selection and allocation strategy that optimally distributes the features and correlations acquired by the network from the images to different tasks, enabling a more refined task differentiation. Moreover, given the challenge of difficult dataset pairing, we employ unsupervised learning techniques and introduce novel Transformer blocks, feedforward networks, and hybrid modules to enhance context relevance. Through extensive experimentation, we demonstrate that our proposed method significantly enhances the performance of color-distorted image restoration.

This study investigated the impact of soil colloidal characteristics on the transfer patterns of different Cu and Cd speciation in contaminated soil treated with three different amendments: lime (L), zero-valent iron (ZVI), and attapulgite (ATP). It seeks to clarify the activation hazards and aging processes of these modifications on Cu and Cd. Compared with the control (CK), the available Cu concentrations treated with amendments reduced in the short term (6 months) by 96.49%, 5.54%, and 89.78%, respectively, and Cd declined by 55.43%, 32.31%, and 93.80%, respectively. Over a 12-year period, there was no significant change in the immobile effect with L, while Cu and Cd fell by 19.06% and 40.65% with ZVI and by 7.63% and 40.78% with ATP. Short- and long-term increases in the readily reducible iron and manganese oxide fraction of Cu and Cd were accompanied by a considerable rise in the concentrations of amorphous iron oxide in the soil and colloid after amendment treatment. This suggested that Cu and Cd were immobilized and stabilized in part by amorphous iron oxide.

Landmark building models typically exhibit intricate structures, posing challenges for retrieval using generic descriptors. To address this challenge, this paper abstracts and simplifies the model into simple topological structures grounded in topological perceptual theory and introduces a novel categorization of landmark building models. Furthermore, based on view, the quotient distance–angle histogram algorithm is proposed for extracting model topological features. This approach facilitates the identification of intricate landmark building models and enhances retrieval performance. In addition, a new projection method is also proposed. Based on the fact that most landmark building models have correct upright direction and the significant topological features predominantly emerge in the top or side views of these models, this method can accelerate the subsequent extraction and matching of shape descriptors by reducing the extraction of model views. Compared with the existing methods, the proposed projection method is more consistent with human visual perception, and the experimental results verify that the proposed method can improve the retrieval performance when classifying the topological structure of 3D landmark building models.

Human papillomavirus (HPV) infection is the main cause of cervical cancer. HPV vaccination is considered an effective way to prevent cervical cancer. Although the vast majority of people experience no obvious adverse reactions after being vaccinated with HPV vaccine, the continuous monitoring of adverse events following immunization is important. Herein, we report the case of a previously healthy young woman who developed unilateral extraocular muscle palsy after receiving the third dose of the Gardasil HPV 9-valent vaccine (9vHPV) and was diagnosed with myasthenia gravis (MG). The patient developed swelling of the left eye on the 3rd day after vaccination and ptosis of the left eyelid on the 18th day after vaccination. She was treated with oral pyridostigmine and methylprednisolone. Her symptoms began to improve after 2 weeks of treatment and resolved completely after 3 weeks. After excluding other possible causes and considering the close temporal relationship between the timing of the 9vHPV vaccination and the onset of symptoms, 9vHPV appears to have triggered MG. To our knowledge, this is the first documented case report of 9vHPV-associated MG in China. Although ocular MG may be a rare adverse event after vaccination with 9vHPV, there is currently no direct evidence establishing a causal relationship; therefore, the safety of 9vHPV remains unquestioned.

Abstract Recent works have shown that by using time‐modulated arrays (TMAs), directional modulation (DM) physical‐layer secured transmitters for orthogonal frequency‐division multiplexing (OFDM) wireless data transfer can be constructed. In this paper, three‐state TMAs are introduced for OFDM DM systems which allow more flexible manipulation of the injected orthogonal artificial noise and hence improve security. In particular, this paper presents for the first time both static and dynamic three‐state time‐modulated OFDM DM systems. Simulated bit error rate (BER) spatial distributions are shown for various system configurations in order to illustrate representative examples of secrecy performance enhancement that can be achieved by the proposed transmitter arrangement.

Abstract Background Childhood asthma has substantial effects on children's health. It is important to identify factors in early life that influence childhood asthma. Accumulating evidence indicates that Helicobacter pylori may protect against allergic diseases. This study aimed to evaluate the relationship between H. pylori infection and pediatric asthma in Chongqing, China. Materials and methods This cross-sectional study included healthy children aged 4–18 years who underwent a 13C urea breath test during medical checkups in 2021. All medical information was extracted from electronic medical records and a big data system. Logistic regression was used to evaluate the association between H. pylori infection and pediatric asthma, and multivariate regression models were adjusted for covariates. Results In our study, 2241 participants, including 1240 boys (55.33%) and 1001 girls (44.67%), underwent urea breath testing (average age: 8.67 ± 2.70 years). Among them, 292 (13.03%) were positive for H. pylori and 152 (6.78%) had asthma. The rates of asthma diagnosis in H. pylori-negative and -positive children were 7.23% and 3.77%, respectively (odds ratio = 1.995; 95% confidence interval: 1.003–3.968; P

Abstract Backscatter communication, an emerging ultra‐low‐power wireless communication paradigm, has been studied as a promising solution for wireless communications in some Internet‐of‐Things (IoT) applications. The required ubiquitous data transmission in the IoT world is demanding information security. Different from mathematical encryption at higher protocol layers, the directional modulation (DM) technology can provide physical‐layer wireless security, which does not require digital and computation resources that are otherwise scarce in low‐power IoT devices. In this paper, a synthesis‐free Van‐Atta backscatter array is constructed and studied. The authors show that a Van‐Atta array can be made to project orthogonal interference upon the backscattered signals in the radio frequency domain. The design details of the Van‐Atta DM array are elaborated, and its efficacy is validated via bit error rate simulations.

Timely, accurate, and efficient extraction of aquaculture sea is important for the scientific and rational utilization of marine resources and protection of the marine environment. To improve the classification accuracy of remote sensing of aquaculture seas, this study proposes an automatic extraction method for aquaculture seas based on the improved SegNet model. This method adds a pyramid convolution module and a convolutional block attention module based on the SegNet network model, which can effectively increase the utilization ability of features and capture more global image information. Taking the Gaofen-1D image as an example, the effectiveness of the improved method was proven through ablation experiments on the two modules. The prediction results of the proposed method were compared with those of the U-Net, SegNet, and DenseNet models, as well as with those of the traditional support vector machine and random forest methods. The results showed that the improved model has a stronger generalization ability and higher extraction accuracy. The overall accuracy, mean intersection over union, and F1 score of the three test areas were 94.86%, 87.23%, and 96.59%, respectively. The accuracy of the method is significantly higher than those of the other methods, which proves the effectiveness of the method for the extraction of aquaculture seas and provides new technical support for automatic extraction of such areas.

BackgroundCholangiocarcinoma (CCA) is a highly heterogeneous malignant tumor, and more than 60% of patients have recurrence and metastasis after surgery. The efficacy of postoperative adjuvant therapy for CCA remains unclear. This study aimed to explore whether adjuvant therapy benefits patients with CCA and examine the independent prognostic factors for overall survival (OS) and progression-free survival (PFS).MethodsPatients with CCA undergoing surgery were retrospectively enrolled in this study from June 2016 to June 2022. The chi-square test or Fisher exact test was used to analyze the correlation between clinicopathologic characteristics. Survival curves were plotted using the Kaplan-Meier method, and the Cox regression model was used for univariate and multivariate analysis to search for independent prognostic factors.ResultsOf the 215 eligible patients, 119 patients received adjuvant therapy, and the other 96 patients did not. The median follow-up was 37.5 months. The median OS of CCA patients with and without adjuvant therapy was 45 and 18 months (P < 0.001), respectively. The median PFS of CCA patients with and without adjuvant therapy was 34 and 8 months (P < 0.001), respectively. The Cox univariate and multivariate regression analysis showed that preoperative aspartate transaminase and carbohydrate antigen 19-9, microvascular invasion, lymph node metastasis, differentiation degree, and adjuvant therapy were independent prognostic factors for OS (all P values < 0.05). Preoperative carbohydrate antigen 125, microvascular invasion, lymph node metastasis, differentiation degree, and adjuvant therapy were independent prognostic factors for PFS (all P values < 0.05). The stratified analysis by TMN stage detected significant differences in the early stages (median OS [mOS]: P = 0.0128; median PFS [mPFS]: P = 0.0209) and advanced stages (mOS and mPFS: both P values < 0.001). Adjuvant therapy was also identified as a significantly favorable prognostic factor for OS and PFS in the early stages and advanced stages.ConclusionPostoperative adjuvant therapy can improve the prognosis of patients with CCA, even in the early stages and advanced stages. All data suggest that adjuvant therapy should be incorporated into the treatment of CCA in all cases, where appropriate.

Introduction: With the worsening global climate problem, carbon peak and carbon neutrality have become crucial objects to realize sustainable development. Regarded as the engine of economic development in the new era, it is worth exploring whether digitalization could contribute to carbon goals. Meanwhile, carbon reduction should not be advocated at the cost of economic recession and contains the risk of reversal when the economy renews in growth.Material and Methods: This paper evaluates carbon efficiency using the total factor non-radial directional distance function, which reflects the economic performance and environmental performance of 246 China’s prefecture-level cities during 2011–2019. Fixed effect and mediation effect models are used to explore the non-linear relationship and transmission channels between digital development and carbon efficiency.Results: It is found that: 1) digital development would hinder carbon efficiency first and then promote it after reaching a certain level; 2) digital development could indirectly affect carbon efficiency through industrial agglomeration, industrial structure upgrading, and industrial electricity productivity in non-linear ways. 3) Heterogeneity exists in the relationship between digital development and carbon efficiency due to different regions and development types.Discussion: Due to digital development itself having high carbon-negative externalities at the initial stage, its impact on carbon efficiency is complex and non-liner even when decomposing through multiple channels. A well-structured development strategy is needed during the digitalization process in order to prompt carbon efficiency.

The Liutex based vortex identification method is superior to previous methods in that it overcomes the issues of threshold problem, shear contamination, etc., with a clear physical meaning that the direction of the Liutex vector represents the local axis of rotation, while the magnitude is equal to twice the angular velocity of the rigid-rotation part of the flow. The current study focuses on the interaction between the Liutex represented rotation and the residual shear part during the development of Λ vortex and hairpin vortex in boundary layer transition. The temporal–spatial evolution and development of typical vortical structures are analyzed based on the Liutex–shear decomposition with particular attention paid to the position and strength changes of Liutex and shear. Vortex core lines are extracted to investigate the mutual interactions between rotation and shear inside vortices. It is demonstrated that for the Λ vortex, spanwise rotating motions are formed at the head region and can persist for a long time under the influence of surrounding shear, while the tail region of the Λ vortex stretches down near the wall but then becomes weaker due to dissipation. High-shear regions tend to be located on top or below the vortices. When the shear layer formed between the legs gets stronger, it will be rolled up to form new vortices. On the one hand, the vortex legs together with the newly formed spanwise vortex consist of a new hairpin vortex, which, in turn, leads to the generation of the second- and third-level hairpin vortices. On the other hand, it also generates many smaller streamwise vortices in the near wall region. The results show that the interaction between Liutex and shear is very important in the development of vortical structures during transition.

The formation and transformation of secondary iron (oxyhydr)oxides and their role in the stabilization of copper (Cu) and zinc (Zn) in acid mine drainage (AMD) after limestone treatment are worth studying to better understand the impacts of limestone AMD treatment. In this study, the wastewater from a copper mine ditch was sampled. Two different doses of limestone (S: 5.33 g L−1 and SS: 8.00 g L−1) were applied to adjust the pH range of the sampled AMD. The concentrations of Fe, Cu and Zn in the supernatant and the levels of iron (oxyhydr)oxides and heavy metals in AMD sediments were dynamically monitored for 300 days to analyze the transformation of the secondary iron mineral phase and the role iron (oxyhydr)oxides play in the removal and stabilization of Cu and Zn. The results showed that the pH rose rapidly to 6.82, decreased to 5.82 on the 150th day, and finally decreased to approximately 4.63 by the 300th day, when the dosage of limestone (S) was 5.33 g L−1. Goethite was the main form of iron oxides in the sediments. As the incubation time increased, so did the content of crystalline Fe (oxyhydr)oxides. In addition, the Cu and Zn content in the fraction of crystalline Fe (oxyhydr)oxides increased as the corresponding iron (oxyhydr)oxide increased. When the high dosage of limestone (8.00 g L−1 or SS) was applied, the pH remained at approximately at 7.46 during the whole period and goethite and lepidocrocite were present in the sediment. Amorphous/ poorly crystalline Fe-oxyhydroxide was the main product after SS limestone dosage, indicating that the risk of Cu and Zn reactivation in the sediment was higher with a higher limestone treatment dosage.

Tumor resistance to apoptosis and the immunosuppressive tumor microenvironment are two main reasons for the poor outcomes of tumor treatment. Pyroptosis is a newly discovered form of programmed cell death, featuring surprising proinflammatory activity. Recent evidence shows that tumor cell pyroptosis leads to strong inflammatory responses and significant tumor regression, which is different from apoptotic cell death. Strategies based on different types of nanoparticles for pyroptosis induction have become a useful tool for tumor treatment. Reactive oxygen species (ROS) is considered an efficient way to cause pyroptosis, and ROS‐based nanotechnologies have been a powerful strategy for pyroptosis induction and cancer treatments. This review covers recent progress in ROS‐induced pyroptosis and nanotherapy to trigger ROS‐mediated pyroptosis in cancer.

Abstract Background Propionic acidemia is a severe inherited metabolic disorder, caused by the deficiency of propionyl-CoA carboxylase which encoded by the PCCA and PCCB genes. The aim of the study was to investigate the clinical features and outcomes, molecular epidemiology and phenotype-genotype relationship in Chinese population. Methods We conducted a retrospective study of 60 Chinese patients diagnosed at Peking University First Hospital from 2007 to 2020. Their clinical and laboratory data were reviewed. The next-generation sequencing was conducted on blood samples from 58 patients. Results Only 5 (8.3%) patients were identified by newborn screening. In the rest 55 patients, 25 had early-onset (≤ 3 months) disease and 30 had late-onset (> 3 months) disease. Neurological abnormalities were the most frequent complications. Five cases detected by newborn screening had basically normal development. Nine (15%) cases died in our cohort. 24 patients (41.4%) harbored PCCA variants, and 34 (58.6%) harbored PCCB variants. 30 (11 reported and 19 novel) variants in PCCA and 28 (18 reported and 10 novel) variants in PCCB mere identified. c.2002G>A and c.937C>T in PCCA, and c.838dupC in PCCB were the most common variants in this cohort, with the frequency of 13.9% (6/44 alleles), 13.9% (6/44 alleles) and 12.5% (8/64 alleles), respectively. There was no difference in clinical features and outcomes between patients with PCCA and PCCB variants. Certain variants with high frequencies and homozygotes may be associated with early-onset or late-onset propionic acidemia. Conclusions Although the genotype–phenotype correlation is still unclear, certain variants seemed to be related to early-onset or late-onset propionic acidemia. Our study further delineated the complex clinical manifestations of propionic acidemia and expanded the spectrum of gene variants associated with propionic acidemia.

The COVID-19 disease caused by infection with SARS-CoV-2 and its variants is devastating to the global public health and economy. To date, over a hundred COVID-19 vaccines are known to be under development, and the few that have been approved to fight the disease are using the spike protein as the primary target antigen. Although virus-neutralizing epitopes are mainly located within the RBD of the spike protein, the presence of T cell epitopes, particularly the CTL epitopes that are likely to be needed for killing infected cells, has received comparatively little attention. This study predicted several potential T cell epitopes with web-based analytic tools and narrowed them down from several potential MHC–I and MHC–II epitopes by ELIspot and cytolytic assays to a conserved MHC–I epitope. The epitope is highly conserved in current viral variants and compatible with a presentation by most HLA alleles worldwide. In conclusion, we identified a CTL epitope suitable for evaluating the CD8+ T cell-mediated cellular response and potentially for addition into future COVID-19 vaccine candidates to maximize CTL responses against SARS-CoV-2.

A promising solution for massive Multiple-Input Multiple-Output (m-MIMO) systems is Hybrid digital-analogue (HDA) beamforming as it offers a balanced trade-off between energy efficiency (EE) and spectral efficiency (SE). The lack of practical demonstrations in the open literature is primarily because those most existing works require a large number of phase shifters (PSs), radio frequency (RF) switches, power dividers (PDs), and power combiners which contribute to high hardware complexity and energy consumption (due to insertion loss). In this paper, we introduce a practical dynamic subarray m-MIMO structure that is based on reconfigurable power dividers (RPDs). The extensive system simulation results, considering hardware imperfection extracted from a practical RPD implementation, indicate that the proposed RPD-based dynamic HDA m-MIMO outperforms the fixed subarray counterpart.

Future broadband satellite communication (SatCom) systems require a high throughput of data transmission, which calls for operation at higher frequency bands. Adaptive coding and modulation (ACM) technology has been considered as a means to obtain improved performance further at these frequencies. However, the ACM protocols in current DVB-S2 and DVB-S2(X) standards do not take the effects that arise from the non-linear link with memory into account, which is generated by the cascade of a high-power amplifier (HPA) and digital root raised cosine (RRC) filters. This paper first reveals the non-linear characteristics of the SatCom link, and transfers this into an equivalent full-linear link with an additive noise source thanks to the pre-distortion algorithm. Using this equivalent modeling, an approach of selecting/adapting the optimum coding, modulation scheme and associated system configurations for a given channel fading level is proposed. Both simulations and experimental test-bed performance are presented to validate the proposed method.

Abstract Background Limited information about Toxoplasma gondii infection in pet cats and their owners is available in China. Methods In this study, blood samples were randomly collected from 306 pet cats and 397 corresponding pet owners in Jilin province, northeastern China. Sera from the pet cats and the pet owners were tested for anti-T. gondii antibodies using an modified agglutination test (MAT) and an enzyme-linked immunosorbent assay (ELISA), respectively. Moreover, the risk factors for T. gondii infection in pet cats and corresponding pet owners were explored. Result In total, 62 sera out of 306 examined pet cats (20.3%) and 18.1% (72/397) pet cat owners were seropositive for T. gondii, respectively. The results of statistical analysis showed that both pet cats and their owners from rural area had significantly higher T. gondii seroprevalence than those from urban area (p