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As one of the most important crops to supply majority plant oil and protein for the whole world, soybean is facing an increasing global demand. Up to now, vast multi-omics data of soybean were generated, thereby providing valuable resources for functional study and molecular breeding. Nevertheless, it is tremendously challenging for researchers to deal with these big multi-omics data, particularly considering the unprecedented rate of data growth. Therefore, we collect the reported high-quality omics, including assembly genomes, graph pan-genome, resequencing and phenotypic data of representative germplasms, transcriptomic and epigenomic data from different tissues, organs and accessions, and construct an integrated soybean multi-omics database, named SoyOmics (https://ngdc.cncb.ac.cn/soyomics). By equipping with multiple analysis modules and toolkits, SoyOmics is of great utility to facilitate the global scientific community to fully use these big omics datasets for a wide range of soybean studies from fundamental functional investigation to molecular breeding.

Familial encephalopathy with neuroserpin inclusion bodies (FENIB), a rare neurogenetic disease, is characterized by progressive cognitive decline and myoclonus and caused by pathogenic variants of the SERPINI1 gene that lead to the formation of neuroserpin inclusion bodies.We described the case of an Asian patient with FENIB associated with a pathogenic variant of SERPINI1 and summarized and analyzed the clinical characteristics of the case. In addition, we conducted a literature review of previously reported patients with this disease.The patient, a 16-year-old Chinese girl, presented with progressive cognitive decline and myoclonus that had started at the age of 11 years. The girl was found to carry a de novo heterozygous c.1175GA (p.G392E) variant of the SERPINI1 gene, which is a pathogenic variant according to the guidelines of the American College of Medical Genetics and Genomics. She had responded poorly to antiseizure medications (ASMs). At the last follow-up, her myoclonus was still out of control, and her self-care ability was poor. Our literature review revealed that 13 similar cases (including 9 cases in male patients) have been reported so far, in which six pathogenetic variations in SERPINI1, including G392E, were responsible for FENIB. All the patients presented with myoclonus, and 12 patients had experienced at least one other type of seizure. Further, as observed in our case, 9 out of 12 patients did not respond to ASMs. Progressive cognitive decline was observed in all the patients, and 10 out of 13 patients had dyskinesia. The median age of disease onset was 21 years, and the median age at the time of death was 33 years. Further, 9 out of 13 patients showed signs of cerebral and/or cerebellar atrophy. Finally, neuroserpin inclusion bodies were identified in six patients who underwent brain biopsy or autopsy.Pathogenic variants of SERPINI1 should be suspected in children with progressive cognitive decline and myoclonus, especially in those with progressive myoclonus epilepsy. Further, gene detection and brain biopsy are important means for the diagnosis of FENIB.

To assess the efficacy of Sanyrene liquid dressing (Urgo Medical) in preventing radiation dermatitis (RD) among patients with cancer after radiotherapy.The authors searched the China National Knowledge Infrastructure, SinoMed, WanFang Data, PubMed, Web of Science, EMBASE, and the Cochrane Library databases for articles published from inception to January 2021.The preliminary search identified 146 studies. After removing duplicates, applying exclusion criteria, and screening titles and abstracts, 19 studies met the inclusion criteria.A standardized form was constructed to extract data from eligible studies. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies.The authors identified a total of 19 studies involving 1,508 patients that assessed the effectiveness of Sanyrene liquid dressing in preventing RD in patients with cancer after radiotherapy. The findings suggested that Sanyrene decreases the total incidence of RD (odds ratio [OR], 5.00; 95% CI, 2.77-9.03; P.00001), as well as the incidence of RD grade 2 (OR, 0.55; 95% CI, 0.36-0.85; P = .007), grade 3 (OR, 0.22; 95% CI, 0.09-0.57; P = .002), and grade 4 (OR, 0.32; 95% CI, 0.13-0.78; P = .01). In addition, in comparison with controls, Sanyrene liquid dressing improves the cure rate (OR, 8.18; 95% CI, 4.03-16.60; P.00001) and delays the occurrence of RD (mean difference, 3.69; 95% CI, 3.03-4.36; P.00001).Sanyrene liquid dressing can decrease both the total incidence of RD and the incidence of RD above grade 2. It also improves the cure rate and delays the occurrence of RD. Thus, Sanyrene may be a superior option for preventing RD after radiotherapy. However, the findings were assessed as moderate- to low-quality evidence and more high-quality trials are needed to support this result.

Reasonable districting plays an important role in the patrolling process. In this paper, workload attributes are considered, and a mixed integer programming model is developed to solve the street patrol districting problem (SPDP). The improved spectral clustering algorithm named spectral clustering algorithm based on the road network (SCRn) and simulated annealing algorithm (SA) are combined. This results in a hybrid algorithm called SCRn-SA. The SCRn-SA algorithm is tested on small examples and real instances in Zhengzhou, China. The experimental results show that the proposed algorithm is effective for solving SPDP. It has better performance when compared to other advanced algorithms.

Purpose Based on the extended resource-based view (ERBV), this paper aims to investigate the relationship between sustainable supply chain management (SSCM), dynamic capabilities (DCs) and enterprise economic performance (EEP). Both the direct effects of SSCM on economic performance and the mediation effect of DCs are investigated. This empirical study also examines the moderating role of firm size. Design/methodology/approach This study applies hierarchical regression analyses to test our hypotheses, and then the mediation test was performed using the macro PROCESS. Data were collected from 178 Chinese manufacturing firms. Findings The findings show that SSCM practices significantly and positively influence both economic performance and DCs. The results indicate that DCs partially mediate the relationship between SSCM practices and EEP. Moreover, firm size has a moderating effect on external SSCM practices that influence EEP, but the moderating effect was not found to be significant for the effects of internal SSCM practices on economic performance and SSCM practices on DCs. Practical implications This study reveals insights into the potential benefits for large enterprises and SMEs related to the utilization of SSCM practices in China and puts forward differentiated suggestions for SSCM practices in large enterprises and SMEs. Originality/value Drawing on the ERBV, this study provides a deeper perspective on the relationship between SSCM and EEP by regarding DCs as a mediating variable and firm size as a moderating variable.

Temozolomide (TMZ) is a standard-of-care chemotherapeutic drug for the treatment of glioblastoma (GBM), but TMZ-acquired resistance limits its therapeutic effect. In this study, TMZ-loaded gold nanoparticles (TMZ@GNPs) with anti-EphA3 modification on the surface (anti-EphA3-TMZ@GNPs) were synthesized for chemical and auxiliary plasma photothermal treatment (GNPs-PPTT), aiming to overcome the problem of glioma resistance to TMZ and improve the therapeutic effects of GBM. The prepared anti-EphA3-TMZ@GNPs were spherical with a particle size of 45.88 ± 1.9 nm, and the drug loading was 7.31 ± 0.38%. In vitro, cell-culture-based experiments showed that anti-EphA3 increased the cellular uptake of GNPs in T98G cells. Upon laser irradiation, the cytotoxicity and apoptosis rate in the anti-EphA3-TMZ@GNPs-treated group were significantly higher than those in the GNPs and nonphotothermal groups (

BackgroundThe CorA / MGT / MRS2 family proteins are an important group of magnesium transporter proteins that maintain magnesium ion homeostasis in plant cells. However, little is known about the MGT functions in wheat.MethodsThe known MGT sequences were used as queries to BlastP against wheat genome IWGSC RefSeq v2.1 assembly (E-value TaMGT gene was obtained from the GFF3 file of the wheat genome data (IWGSCv2.1).The sequence of 1500 bp upstream of the TaMGT genes was extracted from the wheat genome data. The cis-elements were analyzed using PlantCARE online tool.ResultA total of 24 MGT genes were identified on 18 chromosomes of wheat. After functional domain analysis, only TaMGT1A, TaMGT1B, and TaMGT1D had GMN mutations to AMN, while all the other genes had conserved GMN tripeptide motifs. Expression profiling showed that the TaMGT genes were differentially expressed under different stresses and at different growth and development stages. The expression levels of TaMGT4B and TaMGT4A were significantly up-regulated in cold damage. In addition, qRT-PCR results also confirmed that these TaMGT genes are involved in the wheat abiotic stress responses.ConclusionIn conclusion, The results of our research provide a theoretical basis for further research on the function of TaMGT gene family in wheat.

The aim of this study was to investigate the formation rules of 1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP), 1-methyl-9H-pyrido[3,4-b]-indole (Harman), and 9H-pyrido[3,4-b]-indole (Norharman) in chemical model systems containing epicatechin under various reaction conditions and establish their prediction models. The results indicated that at 100-200 °C and pH 5.5-7.5 for 10-90 min, epicatechin inhibited the formation of PhIP, Harman, and Norharman by 32-100, 1-93, and 5-98%, respectively. The exponential growth equation in the growth model with R2 of 0.986-0.997, the second-order equation in the polynomial model with R2 of 0.900-0.949, and the trigonometric function equation in the Fourier model with R2 of 0.513-0.926 were well fitted for the formation of PhIP, Harman, and Norharman at various temperatures, times, and pHs, respectively. The calibration set (R2c) and the prediction set (R2p) of the optimal partial least squares regression prediction model was 0.74 and 0.70 for PhIP, 0.75 and 0.70 for Harman, and 0.90 and 0.91 for Norharman, respectively. The results provide theoretical support to develop technologies or equipment for the real-time synchronous monitoring of PhIP, Harman, and Norharman during meat processing.

AIMS AND OBJECTIVES This study aims to explore the convenience and practicality of the method of establishing buttonholes with indwelling trocars. BACKGROUND Compared with rope-ladder technique, buttonhole cannulation has better applicability for haemodialysis patients, and the method of buttonhole establishment is particularly important. DESIGN Prospective, observational and cohort study. METHODS We conducted a 12-month observational study on 30 patients who used sharp needles to establish buttonholes and 33 patients who used indwelling trocars to establish buttonholes, and compared the differences between the two groups in the buttonhole formation time, patient-reported cannulation pain, buttonhole success rate, AVF-related infection and patency of AVF. The study adhered to STROBE guidelines. RESULTS The buttonhole formation time of the indwelling trocar group is less than that of the sharp needle group (5.48 ± 0.51 vs. 23.23 ± 3.07, p

Purpose Retinol-binding protein 4 (RBP4) has been considered to be related to metabolic related diseases, such as hyperuricemia, obesity, and diabetes mellitus. However, whether nonalcoholic fatty liver disease (NAFLD) is related to RBP4 is unclear. Previous studies on the relationship between NAFLD and RBP4 levels have yielded inconsistent results. Hence, this meta-analysis was aimed to clarify whether circulating RBP4 levels are in relation to the risk of NAFLD. Methods A meta-analysis was performed by applying observational studies to evaluate circulating RBP4 levels and NAFLD. Eligible studies published up to September 23, 2022, were searched in Embase, PubMed, and Cochrane databases. Results In this study, 17 cross-sectional studies involving 8423 participants were included. Results from a random effects model showed that circulating RBP4 levels were higher in NAFLD patients than non-NAFLD (standardized mean difference (SMD) 0.28; 95% confidence intervals (CI): 0.11–0.46, I2: 89.8%). This association was confirmed in the Yellow race. However, no significant association was noted in the Caucasian race. After excluding the morbidly obese Population from the weight loss study (n = 2), the results of the comparison remained largely unchanged (SMD 0.28; 95% CI: 0.10–0.47, I2: 90.8%). Remarkable publication bias was not found. Although considerable heterogeneity was observed among the studies, no potential sources of heterogeneity were found in the subgroup analysis. Diagnostic methods for NAFLD were determined to be a potential source of statistical heterogeneity in meta-regression. Conclusion The findings provide evidence that NAFLD patients exhibit higher levels of circulating RBP4 compared with controls, but high heterogeneity was observed. Thus, a high RBP4 level is probably a potential risk factor for NAFLD. To confirm the causal link between NAFLD and RBP4 level of causality, further prospective cohort studies are needed.

Background High-order chromatin structure plays important roles in gene regulation. However, the diversity of the three-dimensional (3D) genome across plant accessions are seldom reported. Results Here, we perform the pan-3D genome analysis using Hi-C sequencing data from 27 soybean accessions and comprehensively investigate the relationships between 3D genomic variations and structural variations (SVs) as well as gene expression. We find that intersection regions between A/B compartments largely contribute to compartment divergence. Topologically associating domain (TAD) boundaries in A compartments exhibit significantly higher density compared to those in B compartments. Pan-3D genome analysis shows that core TAD boundaries have the highest transcription start site (TSS) density and lowest GC content and repeat percentage. Further investigation shows that non-long terminal repeat (non-LTR) retrotransposons play important roles in maintaining TAD boundaries, while Gypsy elements and satellite repeats are associated with private TAD boundaries. Moreover, presence and absence variation (PAV) is found to be the major contributor to 3D genome variations. Nevertheless, approximately 55% of 3D genome variations are not associated with obvious genetic variations, and half of them affect the flanking gene expression. In addition, we find that the 3D genome may also undergo selection during soybean domestication. Conclusion Our study sheds light on the role of 3D genomes in plant genetic diversity and provides a valuable resource for studying gene regulation and genome evolution.

Purpose This study aimed to explore Chinese breast cancer patients’ quality of sexual life and factors associated with quality of sexual life. Methods In this cross-sectional study, 201 breast cancer patients were required to complete questionnaires assessing characteristic information, cognition and assessment of sexual health, quality of sexual life, self-acceptance and coping style. Finally, hierarchical regression was used to analyze the factors associated with quality of sexual life in Chinese breast cancer patients. Results The average quality of sexual life was 75.14 ± 16.57. Hierarchical regression analysis showed that the associated factors of breast cancer patients’ quality of sexual life included age, education level, type of surgery, cognition and assessment of sexual health, self-acceptance, and avoidance and acceptance-resignation coping styles. Conclusion Concerning age, education level and type of surgery, obtaining correct information on sexual health, improving self-acceptance, and avoiding acceptance-resignation and avoidance coping styles could help breast cancer patients improve their quality of sexual life.

Objectives Extraction of impacted mandibular third molars (IMTMs) is the most common surgery in the Department of Oral and Maxillofacial Surgery. Inferior alveolar nerve (IAN) injury is a rare but severe complication, and the risk is significantly higher for IMTM near the inferior alveolar canal (IAC). The existing surgical method to extract such IMTMs is either not safe enough or is time-consuming. A better surgical design is needed. Materials and Methods From August 2019 to June 2022, 23 patients received treatment by Dr Zhao at Nanjing Stomatological Hospital, Medical School of Nanjing University, to extract their IMTMs and were diagnosed with IMTMs connecting the IAC. Due to high IAN injury risk, these patients undertook coronectomy-miniscrew traction to extract their IMTMs. Results The time between the two surgeries (time of miniscrew traction) was 32.65 ± 2.110 days, which was significantly lower than that of traditional orthodontic traction. No IAJ injury was observed with two-point discrimination testing or reported by patients during follow-up. Other complications such as severe swelling, severe bleeding, dry socket, and limited mouth opening were not observed. Postoperative pain was not significantly higher in the coronectomy-miniscrew traction group than in the traditional IMTM extraction group. Clinical Relevance: For IMTMs connecting the IAC that must be extracted, coronectomy-miniscrew traction is a novel approach to minimize IAN injury risks in a less time-consuming way with a lower possibility of complications.

In parallel with the rapid rise in breast cancer incidence, there is also a noticeable rise in the number of patients who experience persistent negative body image cognition after breast cancer surgery. This study aimed to explore the differences in illness perception, social support, and body image cognition among breast cancer patients with different surgical methods, and the correlation, regression, and mediation among the three variables. The Brief Illness Perception Questionnaire (BIPQ), the Social Support Rating Scale (SSRS) and the Body Image Cognition after Breast Cancer Questionnaire (BIBCQ) were used to evaluate breast cancer patients’ illness perception, social support and body image cognition. Data analyses were performed by descriptive statistics, independent samples t-test, analysis of variance (ANOVA), Pearson correlation, and linear regression. The mediation was explored by the PROCESS V3.3. The study found that breast cancer patients undergoing radical mastectomy (RM) and modified radical mastectomy (MRM) demonstrated more negative illness perception, body image cognition, and lower social support compared with the patients receiving nipple-sparing mastectomy (NSM; p p p

This study sought to analyze long non-coding ribonucleic acid (lncRNA) LINC00273 expression in ovarian cancer tissues, and to preliminarily explore its effect on the growth and invasion of ovarian cancer cells and its influencing mechanism.Quantitative real-time polymerase chain reaction was performed to detect the LINC00273 expression levels of cancerous ovarian tissues and their related cell lines. The ovarian cancer cells with the highest expression of LINC00273 were transfected with a knockdown lentiviral vector targeting the LINC00273 sequence and a negative control plasmid. The effects of the LINC00273 knockdown on the invasion and growth of these cancerous cells were evaluated by clonogenic assays, flow cytometry, EdU (5-Ethynyl-2'-deoxyuridine), Cell Counting Kit-8, and Transwell assays. Western Blot was used to measure the LINC00273 knockdown effects on invasion and migration-related gene expression, and the knockdown effects on the ovarian proliferation ability of the cancer cellsLINC00273 expression was significantly more increased in the cancerous ovarian tissues than the adjacent tissues. The LINC00273 expression of the ovarian cancer cell lines was higher than that of the normal ovarian epithelial cells. LINC00273 knockdown greatly suppressed the proliferative and clonogenic function of these cancerous cells. The flow cytometry results revealed that LINC00273 knockdown notably induced G0/G1 phase arrest in the ovarian cancer cells. LINC00273 knockdown also promoted E-cadherin expression in the ovarian cancer cells, and inhibited vimentin, matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and N-cadherin, expression to inhibit the invasion and migration ability of the ovarian cancer cells. TheLINC00273 is highly expressed in both ovarian cancerous tissues and ovarian cancerous cell lines. LINC00273 knockdown greatly suppressed the proliferative and invasive capabilities of the cancerous ovarian cells. In terms of the molecular process, it may be that the knockdown of LINC00273 promotes E-cadherin and inhibits vimentin, N-cadherin, MMP-2, and MMP-9 expression in cancerous ovarian cells.

Previous studies have shown an association between low serum vitamin B12 levels and the risk of diabetic retinopathy (DR) in type 2 diabetes, but the conclusions from various studies were inconsistent. Therefore, we collected relevant data from various databases to perform a meta-analysis and address the inconsistencies in these studies.We searched PubMed, Embase, Cochrane Library, CNKI, Wanfang and CQVIP for eligible studies published up to April 10, 2022, and performed a meta-analysis using Stata software to assess the association between serum vitamin B12 levels and DR.A total of 15 studies were included in this meta-analysis. Statistical analysis showed that serum vitamin B12 levels were significantly reduced in patients with type 2 diabetic retinopathy ,WMD 95% CI = -68.91 (-76.76, -61.06) (p0.00001, IThis meta-analysis analyzed vitamin B12 in patients with type 2 diabetic retinopathy and emphasized the importance of monitoring serum vitamin B12 levels in patients with type 2 diabetic retinopathy, but this meta-analysis still has deficiencies and limitations, and more clinical studies are needed to confirm this conclusion in the future.

High-fat (HF) diets cause obesity, gut microbial dysbiosis and associated disorders and inflammatory bowel disease (IBD) due to increased intestinal permeability, which is an important reason for chronic inflammation and oxidative stress. This study was to investigate the effects and mechanism by which walnut green husk polysaccharides (WGHP) prevents obesity, oxidative stress, inflammation, liver and colon damage in HF diet induced rats. We found that WGHP alleviated HF-induced abnormal weight gain, disordered lipid metabolism, inflammation, oxidative stress, colonic tissue injury and up-regulate the expression level of colonic tight junction protein in the rats. Besides, the administration of WGHP promoted browning of iWAT and thermogenesis in BAT of HF-fed rats, and improved gut microbiota dysbiosis by increasing the bacterial diversity and reducing the relative abundance of potential pathogenic bacteria in the colon of the rats. Furthermore, WGHP consumption not only increased the SCFAs content but also improved the relative abundance of Prevotellaceae and Allobaculum in the gut of rats. Our results suggest that the protective effect of WGHP on metabolic inflammation caused by HF may be due to the regulation of gut microbiota and SCFAs.

Flavonoids possess the latent ability to protect against sleep disorders. We examined the correlation between daily flavonoid intake and sleep duration, and sleep disorders. We enrolled 8216 participants aged ≥ 20 from the National Health and Nutrition Examination Survey (NHANES, 2007–2010), carrying out a cross-sectional study. Flavonoid intake was collected by dietary intake interview recalls. Logistic regression was utilized to evaluate the association between flavonoid intake sleep duration, and sleep disorders. We used subgroup and interaction analysis to explore differences between subgroups. When adjusting covariates in model 2, anthocyanidins, flavan-3-ols, flavones, flavonols, and the sum of flavonoids were considerably related to insufficient sleep duration (odds ratio (OR) (95% confidence interval (CI)); 0.83 (0.72, 0.95); 0.91 (0.83, 0.98); 0.63 (0.41, 0.98); 0.78 (0.64, 0.94); 0.85 (0.76, 0.95), respectively); the converse association was observed between flavanones, and flavones and the risk of sleep disorders (OR (95% CI); 0.85 (0.77, 0.95); 0.61 (0.41, 0.90), respectively). In relation to insufficient sleep, there were statistically significant interactions between flavonoid consumption and race/ethnicity, and education level. In relation to insufficient sleep, there were statistically significant interactions between flavonoid consumption and working status. In this study, we found that certain flavonoids were linked to increased sleep duration and a lower risk of sleep problems. Our research indicated that flavonoids might be a preventive factor for sleep disorders.

By blocking the DEK protein, DEK-targeted aptamers (DTAs) can reduce the formation of neutrophil extracellular traps (NETs) to reveal a strong anti-inflammatory efficacy in rheumatoid arthritis. However, the poor stability of DTA has greatly limited its clinical application. Thus, in order to design an aptamer with better stability, DTA was modified by methoxy groups (DTA_OMe) and then the exact DEK–DTA interaction mechanisms were explored through theoretical calculations. The corresponding 2′-OCH3-modified nucleotide force field was established and the molecular dynamics (MD) simulations were performed. It was proved that the 2′-OCH3-modification could definitely enhance the stability of DTA on the premise of comparative affinity. Furthermore, the electrostatic interaction contributed the most to the binding of DEK–DTA, which was the primary interaction to maintain stability, in addition to the non-specific interactions between positively-charged residues (e.g., Lys and Arg) of DEK and the negatively-charged phosphate backbone of aptamers. The H-bond network analysis reminded that eight bases could be mutated to probably enhance the affinity of DTA_OMe. Therein, replacing the 29th base from cytosine to thymine of DTA_OMe was theoretically confirmed to be with the best affinity and even better stability. These research studies imply to be a promising new aptamer design strategy for the treatment of inflammatory arthritis.

This study aimed to investigate the protective effects of walnut green husk polysaccharide (WGHP) on liver injury, vascular endothelial dysfunction and disorder of gut microbiota in mice induced by high fructose (HF) diet. The chemical analysis results show that the walnut green husk polysaccharide is a low molecular weight acidic heteropolysaccharide, composed mainly of glucuronic acid, arabinose and galactose. Biochemical analysis showed that WGHP significantly improved glucose metabolism and lipid metabolism and decreased oxidative stress in HF-diet induced obesity mice. Histopathological observation of liver and cardiovascular aorta confirmed the protective effects of WGHP on hepatic steatosis and vascular endothelial dysfunction. Furthermore, 16S rRNA sequencing results demonstrated that WGHP reversed the disorders of gut microbiota caused by HF, decreased the relative abundance of Verrucomicrobia and increased the relative abundance of Deferribacteres at the phylum level, decreased the relative abundance of Akkermansia, Lachnoclostridium and norank_f__Muribaculaceae and increased the relative abundance of Prevotellaceae_UCG-001, Helicobacter, Alloprevotella and Allobaculum at the genus levels. Our results indicate that WGHP may act as a functional polysaccharide for protecting liver and cardiovascular in HF-fed mice.

Most SCN1A missense variants located outside the sodium channel core region show a mild phenotype. However, there are exceptions, because of which it is challenging to determine the correlation between genotype and phenotype. In this study, we aimed to determine whether functional study could be used to determine disease severity in cases with such variants, and elucidate possible genotype-phenotype relationships.Forty-seven patients with SCN1A missense variants were recruited, and one with a Dravet syndrome phenotype with an SCN1A missense variant (c.3811TC/ p.W1271R) located outside the core region was screened with electrophysiological tests. We also reviewed functional SCN1A studies on patients with inconsistent phenotypes and genotypes, and studied the relationship between electrophysiological measurements and clinical phenotype.Patch clamp experiments showed that the W1271R variant caused significantly reduced sodium current, decreased channel voltage sensitivity, loss of channel availability, and prolonged recovery time from inactivation compared with wild type (WT), which ultimately caused a change in loss of function (LOF). Twelve cases of severe SCN1A-related epilepsy with missense variants located outside the channel core region were also included from the functional studies. Nine patients with missense SCN1A variants showed complete (3/9) or partial (6/9) physiological LOF. Two missense SCN1A variants caused physiological gain-and-loss of function (G-LOF), and one caused decreased excitability (DE).Not all missense variants located outside the core region cause a mild phenotype. Although current functional studies in heterologous expression systems do not accurately reflect disease severity caused by SCN1A missense variants, they could be an effective model for generation of data to study the initial effects of SCN1A missense variants.

ERBB3, a member of the ERBB family of receptor tyrosine kinases, plays an important role in cancer, despite its lack of intrinsic carcinogenic mechanism of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). Research on bioinformatics methods through multi-omics, this work proves that ERBB3 gene mutation, methylation modification have extensive regulatory mechanisms on the CESC microenvironment. We found that ERBB3 is involved in carcinogenesis of cervical cancer and is not associated with its prognosis. The carcinogenic mechanism is mainly related to the suppression of the immune system between tumor infiltrating lymphocytes (TILs) and the methylation of the RNA level. Our study indicated ERBB3 is more likely to be a carcinogenic factor than a key prognostic factor for cervical cancer. Methylation of ERBB3 may work as a checkpoint immunotherapy target in CESC, DNA methylation modification of the 4480 base pair downstream of ERBB3 transcription initiation site was the highest.

A new photochemical disulfide-ene reaction system capable of alkylating protein disulfide bonds in seconds has been established. The system is simple, containing acetone and isopropanol for disulfide reduction under 254 nm UV irradiation and norbornene as a highly efficient alkylation reagent. Enhanced characterization of disulfide-rich proteins with significantly shortened analysis time is demonstrated by coupling the reaction online with mass spectrometry.

Pyxinol skeleton is a promising framework of anti-inflammatory agents formed in the human liver from 20S-protopanaxadiol, the main active aglycone of ginsenosides. In the present study, a new series of amino acid-containing derivatives were produced from 12-dehydropyxinol, a pyxinol oxidation metabolite, and its anti-inflammatory activity was assessed using an NO inhibition assay. Interestingly, the dehydrogenation at C-12 of pyxinol derivatives improved their potency greatly. Furthermore, half of the derivatives exhibited better NO inhibitory activity than hydrocortisone sodium succinate, a glucocorticoid drug. The structure–activity relationship analysis indicated that the kinds of amino acid residues and their hydrophilicity influenced the activity to a great extent, as did R/S stereochemistry at C-24. Of the various derivatives, 5c with an N-Boc-protected phenylalanine residue showed the highest NO inhibitory activity and relatively low cytotoxicity. Moreover, derivative 5c could dose-dependently suppress iNOS, IL-1β, and TNF-α via the MAPK and NF-κB pathways, but not the GR pathway. Overall, pyxinol derivatives hold potential for application as anti-inflammatory agents.

Early diagnosis of cervical cancer is essential for a good prognosis. Terahertz wave detection technology is a nondestructive and label-free physical detection technology, which can detect and monitor the cancer cells in real time, especially for patients with deep or inaccessible tumors. In this study, a single-cell-layer microfluidic device was developed. After replacing the optical clearing agent, the characteristics of H8, HeLa and SiHa cell lines in adherent and suspended states were detected. Additionally, the absorption increased with increasing cell density. For the mixed suspension cell samples, principal component analysis-support vector machine method was used to identify benign and malignant cell component. After living cells formaldehyde, changes in cell membrane permeability were evaluated to identify the cell survival status (i.e., dead or living) based on terahertz spectroscopy amplitude differences. Therefore, extending the terahertz spectrum detection to the molecular level can characterize the life essence of cells and tissues.

Hypertension is a chronic disease affecting middle-aged and elderly patients worldwide. Self-management behavior plays a critical role in maintaining blood pressure. Roy adaptation model (RAM), which was proposed by Roy in 1970, has been used to guide hypertension nursing to improve self-management behavior of elderly patients. In the study, to explore the effect of nursing based on the RAM on the self-management behavior of elderly hypertensive patients.A total of 120 elderly hypertensive patients admitted from June 2020 to March 2021 were selected and randomly divided into a control group and observation group based on odd and even numbers of the admission order, with 60 cases in each group. The control group received routine nursing measures while the observation group was given nursing based on the RAM. The self-management behavior, medication compliance, quality of life, and blood pressure control effect were compared between the two groups.The scores of the self-efficacy and self-management behaviors of the observation group and the total score of the scale were higher than those of the control group (P0.05); the observation group patients' medication compliance score was 6.57±1.47, which was higher than that of the control group (4.90±2.16) (P0.01); physiological function, physical pain, energy, social function, emotional function, mental health scores, and total scores of the SF-36 scale in the observation group were all higher than those of the control group (P0.05), while comparison of the general health status dimension scores showed no statistically significant difference; the systolic blood pressure and diastolic blood pressure of the observation group were respectively lower than those of the control group (P0.05); The blood pressure control compliance rate of the observation group was 85.4%, which was higher than that of the control group 64.6% (P0.05).Nursing intervention based on Roy's adaptation model can better enhance the self-efficacy and self-management ability of elderly hypertensive patients, have a positive effect on promoting healthy behavior changes and improving the quality of life, improve medication compliance, and achieve better blood pressure control effects.Chinese Clinical Trial Registry ChiCTR2100052466.

Background The aberrant expression of HER2 is highly associated with tumour occurrence and metastasis, therefore HER2 is extensively targeted for tumour immunotherapy. For example, trastuzumab and pertuzumab are FDA-approved monoclonal antibodies that target HER2-positive tumour cells. Despite their advances in clinical applications, emerging resistance to these two HER2-targeting antibodies has hindered their further application. Somatic mutations in HER2 receptor have been identified as one of the major reasons for resistance to anti-HER2 antibodies. Methods We analysed the frequency of somatic mutations in various tumour types based on TCGA and COSMIC databases. Then, the effect of the most frequent mutation (S310F) on the interaction between pertuzumab and HER2 was analysed by molecular modelling analysis. The effect of the S310F mutation was further evaluated through multiple in vitro binding experiments and antitumour activity assays. Results We found through bioinformatics analysis that S310F, an activating mutation in the HER2 extracellular domain, was the most frequent mutation in HER2. The S310F mutation was shown to confer resistance of HER2-positive tumour cells to pertuzumab treatment. With molecular modelling analysis, we confirmed the possibility that the S310F mutation might disrupt the interaction between pertuzumab and HER2 as a result of a significant change in the critical residue S310. Further functional analyses revealed that the S310F mutation completely abolished pertuzumab binding to HER2 receptor and inhibited pertuzumab antitumour efficacy. Conclusion We demonstrated the loss-of-function mechanism underlying pertuzumab resistance in HER2-positive tumour cells bearing the S310F mutation.

Betulaceae is a well‐defined family of Fagales, including six living genera and more than 160 modern species. Species of the family have high ecological and economic value for the abundant production of wood. However, phylogenetic relationships within Betulaceae have remained partly unresolved, likely due to the lack of a sufficient number of informative sites used in previous studies. Here, we re‐investigate the Betulaceae phylogeny with whole chloroplast genomes from 24 species (17 newly assembled), representing all genera of the family. All the 24 plastomes are relatively conserved with four regions, and each genome is ∼158–161 kb long, with 111 genes. The six genera are all monophyletic in the plastome tree, whereas Ostrya Scop. is nested in the Carpinus clade in the internal transcribed spacer tree. Further incongruencies are also detected within some genera between species. Incomplete lineage sorting and/or hybrid introgression during the diversification of the family could account for such incongruencies. Our dating analysis, based on four fossils, suggests that the most recent common ancestors of the extant genera date back to the mid‐ to late Miocene, and confirms that Betulaceae started to diversify in the upper Cretaceous/early Paleocene. Our results highlight the significance of using more informative sites in resolving phylogenetic relationships. Plastome data and increased taxon sampling will help to better understand the evolutionary history of Betulaceae in the future.

Façade design tends to be diverse with increasing requirements for architectural functions in modern high-rise buildings, leading to various aerodynamic roughness conditions of the building surface. A typical practice is setting vertical ribs on the building façade. This study aims to clarify the effects of vertical ribs on the wind loads and wind-induced responses of high-rise buildings. The models with four vertical rib configurations were tested in the open and suburban exposures using the High-Frequency Force Balance (HFFB) technique in a wind tunnel. The base overturning moments and corresponding responses are demonstrated and compared between models and exposures. Results show that the vertical ribs with a relative width of 4% can not only reduce the mean force coefficients in the along-wind direction but also attenuate the cross-wind vibration by disrupting the regular vortex shedding. Moreover, the half-distributed and full-distributed rib configurations have almost indistinguishable benefit, indicating that the ribs in the corner region of the building façade play a dominant role in reducing the wind-induced responses. Although the cross-wind responses of the building would be less severe in the suburban exposure than those in the open exposure, the reduction rate of the wind-induced responses by the vertical ribs remains almost unchanged.

Buckled hexagonal CSe nanosheet made of earth-abundant elements is investigated for thermoelectric performance by employing the first-principle calculations and the Boltzmann transport theory. The buckled hexagonal CSe sheet is shown to be an indirect-gap semiconductor with a lattice constant of 3.07 A and band gap of 1.51 eV. The maximum power factor of n-type (p-type) CSe sheet is 618 to 483 (9.87 to 7.42) mW m $$^{-1}$$ K $$^{-2}$$ at the temperatures from 300 to 700 K at the carrier concentration of about $$1.17\times 10^{13}$$ ( $$1.24\times 10^{13}$$ ) cm $$^{-2}$$ ). The lattice thermal conductivity of the buckled CSe sheet is in the range of 11.62 to 5.00 W m $$^{-1}$$ K $$^{-1}$$ , and the dimensionless figure of merit of n-type (p-type) CSe sheet is as high as 0.69 to 0.85 (0.18 to 0.40) at the temperatures from 300 to 700 K by choosing appropriate doping level. The high thermoelectric performance indicates that the buckled hexagonal CSe sheet is a promising n-type two-dimensional thermoelectric material.