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Celastrol, triptolide and triptonide are the most significant active ingredients of Tripterygium wilfordii Hook F (TWHF). In 2007, the ‘Cell’ journal ranked celastrol, triptolide, artemisinin, capsaicin and curcumin as the five natural drugs that can be developed into modern medicinal compounds. In this review, we collected relevant data from the Web of Science, PubMed and China Knowledge Resource Integrated databases. Some information was also acquired from government reports and conference papers. Celastrol, triptolide and triptonide have potent pharmacological activity and evident anti-cancer, anti-tumor, anti-obesity and anti-diabetes effects. Because these compounds have demonstrated unique therapeutic potential for acute and chronic inflammation, brain injury, vascular diseases, immune diseases, renal system diseases, bone diseases and cardiac diseases, they can be used as effective drugs in clinical practice in the future. However, celastrol, triptolide and triptonide have certain toxic effects on the liver, kidney, cholangiocyte heart, ear and reproductive system. These shortcomings limit their clinical application. Suitable combination therapy, new dosage forms and new routes of administration can effectively reduce toxicity and increase the effect. In recent years, the development of different targeted drug delivery formulations and administration routes of celastrol and triptolide to overcome their toxic effects and maximise their efficacy has become a major focus of research. However, in-depth investigation is required to elucidate the mechanisms of action of celastrol, triptolide and triptonide, and more clinical trials are required to assess the safety and clinical value of these compounds.

Pseudobagrus ussuriensis is an unscaled fish that is more susceptible to skin damage than scaled fish. To investigate the impacts of hypoxia and reoxygenation on skin and brain immunity, juvenile P. ussuriensis were subjected to hypoxia conditions (DO: 0.8 ± 0.05 mg/L) for durations of 0, 3, 6, and 12 h, followed by 12 h of reoxygenation (DO > 6 mg/L). Histological analysis showed a significant increase in the number of skin mucosal cells after 12 h of hypoxia and a significant decrease after 12 h of reoxygenation when compared to the control group. As the duration of hypoxia increased, an increase in antioxidant (SOD, CAT, GSH, MDA) and immune (cortisol, LZM) physiological parameters of the skin and brain appeared. The results of transcriptomic studies showed that the number of differential genes was greater in skin than in brain. Most of the immune pathways in both tissues under hypoxia conditions were all nonspecific immunity (TNF, IL-17, chemokines), while both tissues maintained their homeostasis through active energy supply and cell cycle regulation. Meanwhile, both physiological parameters and RNA transcriptome results showed that 12 h of reoxygenation could not completely eliminate the negative effects of 12 h of hypoxia. This study offers new insights into the immune responses of P. ussuriensis skin and brain during acute hypoxia and reoxygenation.

ObjectiveTo systematically evaluate the role of blood lipid level in predicting the risk of Alzheimer′s disease (AD). MethodsWe searched Chinese National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database for Chinese Technical Periodicals (VIP), Pubmed, Web of Science, Springer, and Cocharne Library for literatures on the correlation between AD incidence and blood lipid level published in Chinese or English till June 2021 and supplementary manual tracing for some of the references was also conducted. Newcastle-Ottawa-Scale literature quality evaluation scale was adopted to evaluate the quality of the included studies. Statistical analyses were performed with RevMan5.3 software. ResultsA total of 15 eligible studies were selected according to the inclusion and exclusion criteria, and the data on blood lipid level were collected from 1 435 healthy elderly people and 2 162 elderly people with AD. Meta-analysis showed that there was no significant difference in total cholesterol (TC) and triglyceride (TG) level between the AD sufferers and the healthy controls；low-density lipoprotein cholesterol (LDL-C) was significantly higher in the AD sufferers than that in the healthy controls (mean difference [MD] = 3.59，95% confidence interval [95% CI]: 0.98 – 6.21); while, high-density lipoprotein cholesterol (HDL-C) was significantly lower in the AD sufferers than that in the healthy controls (MD = – 3.47，95% CI: – 5.94 – – 0.99). ConclusionHigher LDL-C level but lower HDL-C level may indicate a higher risk of AD in older adults.

BackgroundChemical modification of RNA is a recent hotspot in the field of epigenetics, but the specific mechanism of chemical modification of RNA in aluminum neurotoxicity has not been fully reported.ObjectiveTo investigate the alterations of fat mass and obesity-associated protein (FTO), that demethylates N6-methyladenosine (m6A), and brain-derived neurotrophic factor (BDNF) in different brain regions of rats and rat adrenal pheochromocytoma differentiated cells (PC12 cells) following aluminum exposure.MethodsAnimal experiment: Twenty-four healthy male SD rats were randomly divided into a control group (normal saline) and 10, 20, and 40 μmol·kg−1 exposure groups according to body weight, with 6 rats in each group. Maltol aluminum [Al(mal)3] was injected intraperitoneally every other day for 3 months. Cell experiment: PC12 cells were divided into a control group and 100, 200, and 400 μmol·L−1 exposure groups exposed to Al(mal)3 for 24 h. After exposure, the learning and memory ability of rats was measured by water maze experiment, and the protein expression levels of FTO and BDNF in rat cortex (n=6) and hippocampus (n=6) samples as well as in PC12 cells (n=5) were determined by Western blotting.ResultsThe results of water maze test showed that the escape latency of the 40 μmol·kg−1Al(mal)3 group was higher than those of the control group, the 10 μmol·kg−1Al(mal)3 group, and the 20 μmol·kg−1Al(mal)3 group on day 3, 4, and 5 of training (P

BackgroundOccupational aluminum exposure is closely related to cognitive impairment, and alcohol consumption is also closely related to cognitive dysfunction.ObjectiveTo explore the effects of types of alcohol consumption on cognitive function of occupational aluminum exposed workers.MethodsA total of 181 workers aged from 23 to 56 years were selected by cluster sampling method in an electrolytic aluminum workshop of an aluminum plant in a region and in a maintenance workshop of another plant in the same region from July to August, 2019. Venous blood was collected, and plasma aluminum concentration was determined by inductively coupled plasma mass spectrometry. The study subjects were divided into low and high exposure groups based on the median blood aluminum level and type of work. Their basic information was collected by occupational health examination. Workers' cognitive function was assessed using the Montreal Cognitive Assessment Scale-Beijing Edition. Logistic regression was used to analyze the association between plasma aluminum concentration and cognitive impairment, and between the types of alcohol consumption (including Baijiu, red wine, and beer) and cognitive impairment, Unconditional logistic regression was used to fit multiplicative interaction model as well as additive interaction model of plasma aluminum concentration and the types of alcohol consumption, and to calculate the relative excess relative risk due to interaction (RERI) and attributable proportion due to interaction (AP).ResultsThe M (P25, P75) concentrations of plasma aluminum were 40.01 (25.05, 60.56) µg·L−1 in the total study subjects, 25.16 (17.13, 34.78) µg·L−1 in the low exposure group and 60.56 (47.40, 68.53) µg·L−1 in the high exposure group. After adjusting the type of alcohol consumption, drinking, age, duration of exposure to aluminum, education, marital status, and smoking, the odds ratios for impairments of attention, language expression, and overall cognitive function in the high exposure group were 4.295 (95%CI: 1.912-9.648), 5.687 (95%CI: 1.355-23.867), and 2.720 (95%CI: 1.225-6.040) times of the low exposure group respectively. Besides, after adjusting blood aluminum concentration, total alcohol consumption, age, duration of exposure to aluminum, education, marital status, and smoking, the risk of attention impairment of the Baijiu drinkers was 2.613 (95%CI: 1.054 to 6.837) times of the non-Baijiu drinkers; the risks of impairment of visuospatial abilities and execution functions, language expression, delayed recall, and overall cognitive function of the beer drinkers were 3.165 (95%CI: 1.285-7.797), 17.898 (95%CI: 1.590-201.480), 3.118 (95%CI: 1.215-8.003), and 3.824 (95%CI: 1.736-8.423) times of the non-beer drinkers. There were both additive [RERI (95%CI): 1.745 (1.394-2.097), AP (95%CI): 0.415 (0.201-0.630)] and multiplicative (OR=3.591, 95%CI: 1.393-9.255) interactions between Baijiu intake and plasma aluminum concentration levels on the attention domain. The cognitive impairment attributed to the interactive effects of drinking Baijiu and plasma aluminum concentration in individuals with attention impairment accounted for 41.5%. There were both additive [RERI (95%CI): 5.955 (0.562-11.328), AP (95%CI): 0.829 (0.577-1.081)] and multiplicative (OR=42.174, 95%CI: 5.469-325.252) interactions between beer drinking and plasma aluminum concentration on the overall cognitive function. Among the individuals with overall cognitive impairment, the cognitive impairment caused by the interaction of beer drinking and plasma aluminum concentration accounted for 82.9%.ConclusionOccupation aluminum exposed workers' attention, language expression, and overall cognitive function are closely related to their plasma aluminum concentration. Plasma aluminum concentrations have interactions with Baijiu and beer consumption on cognitive impairment of workers.

IntroductionAutonomous vehicles can have social attributes and make ethical decisions during driving. In this study, we investigated the impact of human-vehicle moral matching on trust in autonomous vehicles and its mechanism.MethodsA 2*2 experiment involving 200 participants was conducted.ResultsThe results of the data analysis show that utilitarian moral individuals have greater trust than deontological moral individuals. Perceived value and perceived risk play a double-edged role in people’s trust in autonomous vehicles. People’s moral type has a positive impact on trust through perceived value and a negative impact through perceived risk. Vehicle moral type moderates the impact of human moral type on trust through perceived value and perceived risk.DiscussionThe conclusion shows that heterogeneous moral matching (people are utilitarian, vehicles are deontology) has a more positive effect on trust than homogenous moral matching (both people and vehicles are deontology or utilitarian), which is consistent with the assumption of selfish preferences of individuals. The results of this study provide theoretical expansion for the fields related to human-vehicle interaction and AI social attributes and provide exploratory suggestions for the functional design of autonomous vehicles.

PurposesDragon boat is a traditional sport in China, but the brain function characteristics of dragon boat athletes are still unclear. Our purpose is to explore the changing characteristics of brain function of dragon boat athletes at different levels before and after exercise by monitoring the changes of EEG power spectrum and microstate of athletes before and after rowing.MethodsTwenty-four expert dragon boat athletes and 25 novice dragon boat athletes were selected as test subjects to perform the 1,000 m all-out paddling exercise on a dragon boat dynamometer. Their resting EEG data was collected pre- and post-exercise, and the EEG data was pre-processed and then analyzed using power spectrum and microstate based on Matlab software.ResultsPost-Exercise, the Heart Rate peak (HR peak), Percentage of Heart Rate max (HR max), Rating of Perceived Exertion (RPE), and Exercise duration of the novice group were significantly higher than expert group (p

The endoplasmic reticulum (ER) is an important cellular organelle, and ER dysfunction has an important impact on a variety of biological processes. In this study, we explored the role of ER stress in cervical cancer by establishing a prognostic model related to ER stress. This study included 309 samples from the TCGA database and 15 pairs of RNA sequencing data before and after radiotherapy. ER stress characteristics were obtained by the LASSO regression model. The prognostic value of risk characteristics was analyzed by Cox regression, Kaplan‒Meier, and ROC curves. The effects of radiation and radiation mucositis on ER stress were evaluated. We found that ER stress-related genes were differentially expressed in cervical cancer and could predict its prognosis. The LASSO regression model suggested that risk genes had a strong ability to predict prognosis. In addition, the regression suggests that the low-risk group may benefit from immunotherapy. Cox regression analysis showed that FOXRED2 and N staging could be independent factors affecting prognosis. ERN1 was significantly affected by radiation and may be related to the occurrence of radiation mucositis. In conclusion, ER stress activation might have a high value in the treatment and prognosis of cervical cancer and has good clinical prospects.

Constipation is a common gastrointestinal symptom characterized by intestinal motility disorder. The effects of Platycodon grandiflorum polysaccharides (PGP) on intestinal motility have not been confirmed. We established a rat model of constipation induced by loperamide hydrochloride to elucidate the therapeutic effect of PGP on intestinal motility disorder and to explore the possible mechanism. After PGP treatment (400 and 800 mg/kg) for 21 d, PGP clearly relieved gastrointestinal motility, including fecal water content, gastric emptying rate, and intestinal transit rate. Moreover, the secretion of motility-related hormones, gastrin and motilin, were increased. Enzyme-linked immunosorbent assay, western blot, immunohistochemistry, and immunofluorescence results confirmed that PGP significantly increased the secretion of 5-hydroxytryptamine (5-HT) and the expression of related proteins, such as tryptophan hydroxylase 1, 5-HT4 receptor, and transient receptor potential ankyrin 1. 16S rRNA gene sequencing showed that PGP significantly increased the relative abundance of Roseburia, Butyricimonas, and Ruminiclostridium, which were positively correlated with 5-HT levels. However, the relative abundance of Clostridia_UCG-014, Lactobacillus, and Enterococcus were decreased. PGP improved intestinal transport by regulating the levels of 5-HT, which interacts with the gut microbiota and the intestinal neuro-endocrine system, further affecting constipation. Overall, PGP is a potential supplement for the treatment of constipation.

The Chinese central government has been running an intensive exchange program called the Mainland China–Hong Kong Ten Thousand Student Exchange Program since 2012 to support local Hong Kong university students’ visits to mainland China, with the aim of promoting exchange and regional cooperation between Hong Kong and mainland China. However, little is known about local Hong Kong university students’ views on regional cooperation and whether the program is effective in changing their views. Using a randomized experimental design, we find that most students hold positive views on regional cooperation between Hong Kong and mainland China, but a considerable percentage of students oppose integration with mainland China. We also find that the program is effective in positively changing students’ views on certain aspects of regional cooperation related to the free trade zones and the Hong Kong–Zhuhai–Macau Bridge, but is not significantly effective on other aspects of regional cooperation. This study provides the first causal quantitative evidence regarding the impact of the mainland China–Hong Kong exchange program on local university students’ views regarding regional cooperation. The findings help inform the public about the prospect of regional cooperation and offer policy implications on youth exchange between mainland China and Hong Kong.

Abstract Background Hereditary hearing loss is a heterogeneous class of disorders that exhibits various patterns of inheritance and involves many genes. Variants in the EYA4 gene in DFNA10 are known to lead to postlingual, progressive, autosomal dominant nonsyndromic hereditary hearing loss. Patients and methods We collected a four-generation Chinese family with autosomal-dominant nonsyndromic hearing loss (ADNSHL). We applied targeted next-generation sequencing (TNGS) in three patients of this pedigree and whole-genome sequencing (WGS) in the proband. The intrafamilial cosegregation of the variant and the deafness phenotype were confirmed by PCR, gap-PCR and Sanger sequencing. Results A novel CNV deletion at 6q23 in exons 8–11 of the EYA4 gene with a 10 bp insertion was identified by TNGS and WGS and segregated with the ADNSHL phenotypes. Conclusions Our results expanded the variant spectrum and genotype‒phenotype correlation of the EYA4 gene and autosomal dominant nonsyndromic hereditary hearing loss in Chinese Han individuals. WGS is an accurate and effective method for verifying the genomic features of CNVs.

This paper proposes a fast direction of arrival (DOA) estimation method based on positive incremental modified Cholesky decomposition atomic norm minimization (PI-CANM) for augmented coprime array sensors. The approach incorporates coprime sampling on the augmented array to generate a non-uniform, discontinuous virtual array. It then utilizes interpolation to convert this into a uniform, continuous virtual array. Based on this, the problem of DOA estimation is equivalently formulated as a gridless optimization problem, which is solved via atomic norm minimization to reconstruct a Hermitian Toeplitz covariance matrix. Furthermore, by positive incremental modified Cholesky decomposition, the covariance matrix is transformed from positive semi-definite to positive definite, which simplifies the constraint of optimization problem and reduces the complexity of the solution. Finally, the Multiple Signal Classification method is utilized to carry out statistical signal processing on the reconstructed covariance matrix, yielding initial DOA angle estimates. Experimental outcomes highlight that the PI-CANM algorithm surpasses other algorithms in estimation accuracy, demonstrating stability in difficult circumstances such as low signal-to-noise ratios and limited snapshots. Additionally, it boasts an impressive computational speed. This method enhances both the accuracy and computational efficiency of DOA estimation, showing potential for broad applicability.

Foamy viruses are members of the Retroviridae family’s Spumaretrovirinae subfamily. They induce cell vacuolation and exhibit a foamy pathogenic impact after infecting cells. DACH1 (dachshund family transcription factor 1) is a crucial cytokine linked to tumor development, and is associated with the growth of many different malignant tumor cells. Additionally, DACH1 suppresses pancreatic cell proliferation and is involved in diabetes insulin signaling. Prototype foamy viruses (PFVs) were used for the investigation of the regulatory mechanism of FVs on cellular DACH1 expression. The results show that DACH1 expression in PFV-infected cells was inconsistent at both the transcriptional and protein levels. At the transcriptional level, DACH1 was significantly activated by PFV transactivator Tas, and dual-luciferase reporter gene tests, EMSA, and ChIP assays found a Tas response element of 21 nucleotides in the DACH1 promoter. PFV and Tas did not boost the levels of DACH1 protein in a manner consistent with the high levels of DACH1 transcription expression. It was noted that Tas increased the expression of the Ser/Thr protein phosphatase PPM1E, causing PPM1E-mediated post-translational SUMOylation alterations of DACH1 to prompt DACH1 to degrade. The reason for DACH1 protein degradation is that DACH1 inhibits PFV replication. To sum up, these findings show that PFV upregulated the transcription of DACH1, while urging its protein into PPM1E-mediated SUMOylation, to eliminate the adverse effect of DACH1 overexpression of host cells on viral replication and promote virus survival.

Aims. This study explores the effects of curcumin as a therapeutic agent against oral squamous cell carcinoma (OSCC). Methods. We acquired the targets of curcumin from three digital databases, including the Comparative Toxicogenomics Database, Search Tool for Interactions of Chemicals, and SwissTargetPrediction. Then, we identified the differentially expressed genes (DEGs) and the weighted gene coexpression network analysis-based key modules using the expression profiles of GSE23558 to acquire the OSCC-related genes. Additionally, the GeneCards and Online Mendelian Inheritance in Man databases were also used to identify the OSCC-related genes. Finally, curcumin-OSCC interaction genes were obtained by overlapping curcumin targets and OSCC-related genes. The enrichment analysis was performed by the ClusterProfiler algorithm and Metascape, respectively. Then, a protein-protein interaction network was created, and the maximal clique centrality algorithm was used to identify the top 10 hub genes. Besides, we examined the expression levels of hub genes in OSCC using The Cancer Genome Atlas database. Results. 927 DEGs were identified, including 308 upregulated ones and 619 downregulated ones. The cluster one-step network construction function of the WGCNA algorithm recognized a soft-thresholding power of 6, and 9083 genes were acquired. 2591 OSCC-related genes were obtained by overlapping the GSE23558-identified genes and the OSCC-related genes from disease target bases. Finally, we identified 70 candidate drug-disease interaction genes by overlapping the disease-related genes with the curcumin target. The enrichment analysis suggested that response to oxidative stress, epithelial cell proliferation, and AGE/RAGE pathway might involve in the effect of curcumin on OSCC. The topologic study identified the ten hub genes, including VEGFA, AKT1, TNF, HIF1A, EGFR, JUN, STAT3, MMP9, EGF, and MAPK3. A significant difference was observed in VEGFA, AKT1, TNF, HIF1A, EGFR, MMP9, EGF, and MAPK3 expression levels between head and neck squamous cell carcinoma and the normal controls. However, no significant difference was observed in JUN (P=0.14) and STAT3 (P=0.054). Conclusion. This study provided an overview and basis for the potential mechanism of curcumin against OSCC. The following experiments should be performed to further understand the effectiveness and safety of curcumin in treating OSCC.

Graphical Abstract

Percutaneous transhepatic cholangiodrainage (PTCD) and percutaneous transhepatic biliary stenting (PTBS) may be used as a palliative treatment for inoperable patients with malignant biliary obstruction (MBO) to improve the prognosis and their quality of life. However, acute pancreatitis is a common and severe complication that cannot be ignored after PTCD and PTBS in patients with MBO. A few cases may develop severe pancreatitis with a higher mortality rate. In this study, we summarize the known risk factors for acute pancreatitis after percutaneous biliary interventional procedures and investigate possible risk factors to reduce its occurrence by early identifying high-risk patients and taking appropriate measures.

Coal workers’ pneumoconiosis (CWP) is a fatal occupational disease caused by inhalation of coal dust particles, which leads to progressive pulmonary fibrosis. Recently, as new signal carriers for intercellular communication, exosomal miRNAs have been validated in the pathogenesis of multiple diseases. However, the research on exosomal miRNAs in CWP is still in the preliminary stage. Here, using miRNA sequencing, exosomal miRNA profiles in bronchoalveolar lavage fluid (BALF) from rats with pulmonary fibrosis induced by coal dust particles were analyzed, and the underlying biological function of putative target genes was explored by GO term analysis and KEGG pathway enrichment analysis. According to the results, intratracheal instillation of coal dust particles can alter the exosomal miRNAs expression in the BALF of rats. Further bioinformatics analysis provided some clues to reveal their function in pathological process of pneumoconiosis. More importantly, we identified 4 differentially expressed exosomal miRNAs (miRNA-21–5p, miRNA-29a-3p, miRNA-26a-5p, and miRNA-34a-5p) by qRT‑PCR and further verified the temporal changes in the expression of these exosomal miRNAs in animal models from 2 weeks to 16 weeks postexposure. In addition, we conducted a preliminary study on Smad7 as a potential target of miRNA-21–5p and found that exosomal miRNA 21–5p/Smad7 may contribute to the pulmonary fibrosis induced by coal dust particles. Our study confirmed the contribution of exosomal miRNAs to coal dust particle-induced pulmonary fibrosis and provided new insights into the pathogenesis of CWP.

Background and objective: Doxorubicin (DOX) is one of the most commonly used antineoplastic agents; however, its considerable nephrotoxicity restricts its clinical use. Kaempferol (KPF), a naturally-occurring flavonoid, possesses various biological benefits, including anti-tumor activity that has garnered increasing attention. This study aimed to evaluate the possible reno-protective role of KPF in DOX nephrotoxicity. Methods: Male BALB/c mice were injected with DOX via the tail vein to imitate renal damage. Their body and kidney were weighed after 2 weeks of KPF therapy, and urine, serum, and tissue samples were obtained to establish proteinuria, serum creatinine, and pathological alterations. The variations in SOD, GSH, CTA, MDA, and SOD2 expression in renal tissues were measured, and p-ASK1, p-p38, and P-JNK were evaluated by western blot. Cell viability was detected using MTT tests. Apoptosis was assessed by TUNEL, Hoechst 33342, PI staining, and western blot. Fluorescent ROS probes were used to assess oxidative cell damage. Results: KPF ameliorated DOX-induced renal injury, improved proteinuria and renal function, restored GSH content, SOD activity and CTA activity in kidneys, inhibited the overproduction of MDA, and suppressed DOX-induced activation of the MAPK signaling pathway. In NRK-52E cells, KPF significantly inhibited DOX-induced ROS overproduction, restrained the activation of MAPK signaling pathway, and alleviated DOX-induced cell morphological damage and loss of cell viability, While it did not affect the toxicity of DOX to 4T1 cells. Conclusion: KPF provides a protective effect against DOX-induced nephrotoxicity while maintaining the cytotoxicity of DOX in breast cancer cells, thereby it may provide a viable solution to lessen renal toxicity in cancer patients receiving DOX.

Aluminum is a known neurotoxin that can induce Aβ deposition and abnormal phosphorylation of tau protein, leading to Alzheimer disease (AD)-like damages such as neuronal damage and decreased learning and memory functions. In this study, we constructed a rat model of subchronic aluminum maltol exposure, and the whole-transcriptome sequencing was performed on the hippocampus of the control group and the middle-dose group. A total of 167 miRNAs, 37 lncRNAs, 256 mRNAs, and 64 circRNAs expression changed. The Kyoto Encyclopedia of Genes and Genomes showed that PI3K/AKT pathway was the most enriched pathway of DEGs, and IRS1 was the core molecule in the PPI network. circRNA/lncRNA-miRNA-mRNA networks of all DEGs, DEGs in the PI3K/AKT pathway, and IRS1 were constructed by Cytoscape. Molecular experiment results showed that aluminum inhibited the IRS1/PI3K/AKT pathway and increased the content of Aβ and tau. In addition, we also constructed an AAV intervention rat model, proving that inhibition of miR-96-5p expression might resist aluminum-induced injury by upregulating expression of IRS1. In general, these results suggest that the ceRNA networks are involved in the neurotoxic process of aluminum, providing a new strategy for studying the toxicity mechanism of aluminum and finding biological targets for the prevention and treatment of AD.

Acorus calamus var. angustatus Besser (ATT) is a traditional herb with a long medicinal history. The volatile oil of ATT (VOA) does possess many pharmacological activities. It can restore the vitality of the brain, nervous system and myocardial cells. It is used to treat various central system, cardiovascular and cerebrovascular diseases. It also showed antibacterial and antioxidant activity. Many studies have explored the benefits of VOA scientifically. This paper reviews the extraction methods, chemical components, pharmacological activities and toxicology of VOA. The molecular mechanism of VOA was elucidated. This paper will serve as a comprehensive resource for further carrying the VOA on improving its medicinal value and clinical use.

Abstract Background Nonalcoholic fatty liver disease (NAFLD) and gallstone disease (GSD) often coexist in the general population owing to shared risk factors. This study explored the relationship between NAFLD and GSD in patients with type 2 diabetes. Methods We conducted a retrospective cross-sectional analysis of 4325 patients with type 2 diabetes. GSD and NAFLD were confirmed using ultrasonography. GSD was defined as either asymptomatic gallstones or previous cholecystectomy, and each was analyzed separately. Result There was no significant difference in the prevalence of GSD between patients with and without NAFLD (23.8% vs. 21.2%, P = 0.15). After case–control matching (1:1) of baseline data such as age, sex, duration of diabetes, and HbA1c between patients with and without NAFLD, there was still no significant difference in the prevalence of GSD (25.5% vs. 23.6%, P = 0.15). The prevalence of NAFLD in patients with asymptomatic gallstones was lower than that of patients without GSD (38.6% vs. 47.3%, P

An apparel product has a unique feature other than other products in that apparel product design must consider three categories of design requirements, namely function (governed by natural sciences), comfort (governed by ergonomics), and pleasure (governed by aesthetics and psychology). This paper proposes a general design theory for apparel products. The theory is based on Axiomatic Design Theory (ADT), which is for the functional aspect of products, particularly by adapting ADT to apparel product design, to which all the aspects (function, comfort, pleasure) need to be considered. The proposed theory is thus called the Axiomatic Design Theory For Apparel (ADT-FA). The ADT-FA has two axioms. Axiom 1 (apparel) concerns coupling in the design requirement, and Axiom 2 (apparel) concerns redundancy in the design parameter. The proposed theory is preliminarily validated with the Zoot suit, which is well known in the community of apparel design. The work opens an avenue for more validations in future.

Background Guidelines recommend catheter ablation of atrial fibrillation (AFCA) as an option for rhythm control. Studies have shown that Black patients are less likely to undergo AFCA compared with White patients. We investigated whether differences in referral patterns play a role in this observed disparity. Methods and Results Using an integrated repository from the electronic medical record at Northwestern Medicine, we conducted a retrospective cohort study of outpatients with newly diagnosed atrial fibrillation. Baseline characteristics by race and ethnicity were compared. Logistic regression models adjusted for socioeconomic and health factors were constructed to determine the association between race and ethnicity and binary dependent variables including referrals and visits to general cardiology and cardiac electrophysiology (EP) and AFCA. Of 5445 patients analyzed, 4652 were non‐Hispanic White (NHW) and 793 were non‐Hispanic Black (NHB). In adjusted models, NHB patients initially diagnosed with atrial fibrillation in internal medicine and primary care had a significantly greater odds of referral to general cardiology; among all patients in the cohort, there was no significant difference in the odds of referral to EP between NHB and NHW patients; and there were no differences in the odds of completing a visit in general cardiology or EP. Among patients completing an EP visit, NHB patients were less likely to undergo AFCA (odds ratio, 0.63 [95% CI, 0.40–0.98], P=0.040). Conclusions Similar referral rates to general cardiology and EP were observed between NHB and NHW patients. Despite this, NHB patients were less likely to undergo AFCA.

Salvianolic acid B is extracted from the roots and rhizomes of Danshen (Salvia miltiorrhiza Bge., family Labiatae). It is a water-soluble, weakly acidic drug that has demonstrated antitumor and anti-inflammatory effects on various organs and tissues such as the lung, heart, kidney, intestine, bone, liver, and skin and protective effects in diseases such as depression and spinal cord injury. The mechanisms underlying the protective effects of salvianolic acid B are mainly related to its anti-inflammatory, antioxidant, anti- or pro-apoptotic, anti- or pro-autophagy, anti-fibrotic, and metabolism-regulating functions. Salvianolic acid B can regulate various signaling pathways, cells, and molecules to achieve maximum therapeutic effects. This review summarizes the safety profile, combination therapy potential, and new dosage forms and delivery routes of salvianolic acid B. Although significant research progress has been made, more in-depth pharmacological studies are warranted to identify the mechanism of action, related signaling pathways, more suitable combination drugs, more effective dosage forms, and novel routes of administration of salvianolic acid B.

Droplet-based microfluidics with the characteristics of high throughput, low sample consumption, increasing reaction speed, and homogeneous volume control have been demonstrated as a useful platform for biomedical research and applications. The traditional fabrication methods of droplet microfluidics largely rely on expensive instruments, sophisticated operations, and even the requirement of an ultraclean room. In this manuscript, we present a 3D printing-based droplet microfluidic system with a specifically designed microstructure for droplet generation aimed at developing a more accessible and cost-effective method. The performance of droplet generation and the encapsulation capacity of the setup were examined. The device was further applied to measure the variation in cell viability over time and monitor the cell’s blebbing activity to investigate its potential ability and feasibility for single-cell analysis. The result demonstrated that the produced droplets remained stable enough to enable the long-time detection of cell viability. Additionally, cell membrane protrusions featuring the life cycle of bleb initiation, expansion, and retraction can be well-observed. Three-dimensional printing-based droplet microfluidics benefit from the ease of manufacture, which is expected to simplify the fabrication of microfluidics and expand the application of the droplet approach in biomedical fields.

In order to alleviate the structural vibrations induced by traffic loads, in this paper, a phonon crystal plate with functionally graded materials is designed based on local resonance theory. The vibration damping performance of the phonon crystal plate is studied via finite element numerical simulation and the band gap is verified via vibration transmission response analysis. Finally, the engineering application mode is simulated to make it have practical engineering application value. The results show that the phonon crystal plate has two complete bandgaps within 0~150 Hz, the initial bandgap frequency is 0.00 Hz, the cut-off frequency is 128.32 Hz, and the internal ratio of 0~100 Hz is 94.13%, which can effectively reduce the structural vibration caused by traffic loads. Finally, stress analysis of the phonon crystal plate is carried out. The results show that phonon crystals of functionally graded materials can reduce stress concentration through adjusting the band gap. The phonon crystal plate designed in this paper can effectively suppress the structural vibration caused by traffic loads, provides a new method for the vibration reduction of traffic infrastructure, and can be applied to the vibration reduction of bridges and their auxiliary facilities.

The role and mechanism of lncRNA XIST (XIST) in the development of rheumatoid arthritis (RA) was explored in this study. RT-qPCRs were performed to detect the expression of XIST and miR-126-3p in synovial tissues and cells. Target gene prediction and luciferase gene reporter assay were used to validate downstream target genes of XIST. MTT assay, EdU staining and Annexin V/PI staining were performed to explore the effects of XIST and miR-126-3p on cell proliferation and apoptosis. Western blotting analysis was used to detect the expression of related proteins. We found that the expression levels of XIST in tissues and cells were significantly higher than that in normal tissues and cells. Down-regulation of XIST could inhibit cell proliferation rate and increase apoptosis rate. Luciferase gene reporter assay showed that miR-126-3p was a downstream target gene of XIST. Overexpression of miR-126-3p significantly inhibited RA-FLS cell proliferation and induced RA-FLS cell apoptosis. In addition, down-regulation of XIST could increase the ratio of caspase-3 and Bax/Bcl-2. In addition, overexpression of miR-126-3p could inhibit the NF-κB signalling pathway by reducing the expression levels of p-p65 and p-IκBα in RA-FLS cells. In conclusion, down-regulation of XIST can inhibit the proliferation of synovial fibroblasts by increasing the expression levels of miR-126-3p/NF-κB, thereby inhibiting the occurrence and development of RA.

Objective:Acanthopanax senticosus (Rupr. et Maxim.) Harms (ASH) is a traditional herbal medicine widely known for its antifatigue and antistress effects, as well as tonifying qi, invigorating spleen and kidney, and tranquilizing the mind. Recent evidence suggests that ASH has a therapeutic effect on major depressive disorder (MDD), but its mechanism is still unclear. The current study aimed to investigate the effect of ASH on MDD and potential therapeutic mechanisms.Materials and Methods: The chemical compound potential target network was predicted based on network pharmacology. Simultaneously, chronic unpredictable mild stress (CUMS) model mice were orally administrated ASH with three dosages (400, 200, and 100 mg/kg) for 6 weeks, and hepatic metabolomics based on gas chromatography–mass spectrometry (GC–MS) was carried out to identify differential metabolites and related metabolic pathways. Next, the integrated analysis of metabolomics and network pharmacology was applied to find the key target. Finally, molecular docking technology was employed to define the combination of the key target and the corresponding compounds.Results: A total of 13 metabolites and four related metabolic pathways were found in metabolomics analysis. From the combined analysis of network pharmacology and metabolomics, six targets (DAO, MAOA, MAOB, GAA, HK1, and PYGM) are the overlapping targets and two metabolic pathways (glycine, serine, and threonine metabolism and starch and sucrose metabolism) are the most related pathways. Finally, DAO, MAOA, MAOB, GAA, HK1, and PYGM were verified bounding well to their corresponding compounds including isofraxidin, eleutheroside B1, eleutheroside C, quercetin, kaempferol, and acacetin.Conclusion: Based on these results, it was implied that the potential mechanism of ASH on MDD was related to the regulation of metabolism of several excitatory amino acids and carbohydrates, as well as the expression of DAO, MAOA, MAOB, GAA, HK1, and PYGM.

In order to reduce the carbon emission of the port and build a green port, a polymorphic distributed energy management method for the low carbon port microgrid with carbon capture and carbon storage device is proposed. Firstly, this paper presents a low carbon port microgrid in a polymorphic network environment to realize the information interaction among energy subjects in different modes and improve network communication performance among port power generation device, main grid, carbon capture and carbon storage device. Secondly, the energy management model of low-carbon port microgrid is constructed considering the additional carbon capture device and carbon storage device in the port. Then, based on the multi-agent consensus algorithm, a distributed energy management method is proposed, which is respectively oriented to the grid-connected operation mode, island operation mode and switching operation mode of the port microgrid, so as to achieve the economic, low carbon and reliable operation of the port microgrid. Finally, the simulation results of Matlab verify the effectiveness of the proposed method.

Objective Lung cancer has high morbidity and mortality. We aimed to determine the value of netrin-1 for the diagnosis and chemotherapeutic monitoring of lung cancer. Methods Thirty pairs of lung cancer tissues and serum were collected. Netrin-1 expression was detected by immunohistochemistry and enzyme-linked immunosorbent assay. Netrin-1 expression was downregulated in A549 cells using small interfering RNA, and the effect of netrin-1 on cisplatin-induced lung cancer cell apoptosis was determined by flow cytometry. Results Netrin-1-positivity was significantly higher in lung cancer tissues than in paracarcinoma tissues and high expression of netrin-1 was closely related to a poor prognosis. Serum netrin-1 levels were also significantly higher in lung cancer patients than in healthy donors, and were higher in patients with lung cancer before the beginning of chemotherapy compared with after the completion of four cycles of chemotherapy. Netrin-1 knockdown increased the rate of cisplatin-induced apoptosis in A549 cells. Conclusions Netrin-1 expression was increased in tissues and serum from lung cancer patients and decreased after chemotherapy, suggesting that it may be a potential diagnostic marker and indicator of chemosensitivity. Netrin-1 may participate in cisplatin resistance by reducing apoptosis, thus providing a new strategy for addressing chemoresistance in patients with lung cancer.

Energy cooperation is the forerunner and main engine of the Belt and Road Initiative. In the past ten years, hundreds of oil and gas cooperation projects have been operated in the countries along the Belt and Road and other countries by Chinese petroleum companies, with fruitful results achieved. The technical service and engineering construction is an important part of the cooperation. As the most important content for construction of oil and gas pipeline, hydrostatic testing is a most common method for verification of pipeline integrity. Based on the design experience of gathering pipelines in the oil and gas fields of the cooperation projects in Middle East and Africa, the 13 hydrostatic testing standards of the international organizations and petroleum corporations such as ASME, API, ISO, BSI, IPS, Saudi Aramco, ADNOC, Shell, Total and BP were sorted out, and the requirements for the test pressure and pressure holding time of the water quality test, strength test and tightness test were compared and analyzed. The research results are expected to provide reference for the design and construction of gathering pipelines in oversea oil and gas fields.

Abstract Background Omega-3 polyunsaturated fatty acids (PUFAs) produce lipid mediators with both anti-inflammatory and pro-resolution properties, including resolvins. The purpose of this study was to detect serum resolvin E1 (RVE1) levels in Hashimoto’s thyroiditis (HT) patients and healthy controls (HCs) and to evaluate the relationship of RVE1 with thyroid autoimmunity. Methods A total of 57 participants were recruited, including 30 untreated HT patients and 27 age- and sex‐matched HCs. The levels of RVE1 in serum were measured via enzyme-linked immunosorbent assay (ELISA). An electrochemiluminescence immunoassay was used for the measurement of thyroid-stimulating hormone (TSH), total T4 (TT4), TT3, free T4 (FT4), FT3, anti-thyroid peroxidase antibody (TPOAb) and anti-thyroglobulin antibody (TgAb) levels. Hemogram tests and routine biochemical analyses were performed on each sample. Results The serum level of RVE1 of HT patients (24.09, 15.76–34.38 pg/mL) was significantly lower than that of healthy controls (28.51, 20.76–51.23 pg/mL) (P = 0.027). RVE1 levels showed a downward trend with increasing TgAb levels (P for trend = 0.001). Multivariable ordinal logistic regression analysis showed that RVE1 levels were negatively correlated with increasing TgAb levels in both the unadjusted (OR = 0.9446, 95 % CI = 0.9111–0.9782, P = 0.002) and adjusted models (OR = 0.9380, 95 % CI = 0.8967–0.9811, P = 0.005). Conclusions Decreased RVE1 levels might be a sign that HT is associated with inflammatory resolution dysfunction. RVE1 may serve as a protective factor against increased TgAb levels.

Histamine receptors are effective targets for allergy treatments and antihistamines are the first choice of many allergic disorders, but the exact mechanism of agonist binding and receptor activation remain unknown. Here, the authors present the cryo-EM structure of histamine-bound H1R/Gq complex and propose a mechanism of ligand induced receptor activation.

The initial and induced anisotropy has a significant effect on the mechanical properties of soft soil in preloading engineering. However, there is a lack of unified research methods for the initial and induced anisotropy. Discrete element method is adopted in this study, and the length-width ratio of particles is used as the quantitative evaluation index. Five types of initial anisotropy samples with different deposition angles are generated. The effects of initial anisotropy and induced anisotropy on the mechanical properties of soft soil are studied by vertical and horizontal loading. At the micro level, the contact form and rotation angle of particles are examined from the point of view of particles, and the development trend of coordination number and contact normal to anisotropy is studied from the point of view of contact. The relationship between shear strength index and anisotropy is explored. The results show that initial and induced anisotropy influences the mechanical properties of the samples. When the loading direction is perpendicular to the soft soil deposition direction, the soil mass has the maximum peak strength. In the particle contact form, the proportion of surface contact gradually increases with loading. The initial modulus and shear strength are influenced. The coordination number and contact normal anisotropy have different evolutions under the influence of particle contact form, and tend to be stable at the later loading stage. In terms of shear strength parameters, the initial anisotropy will increase the cohesion of the sample, and the induced anisotropy will mainly change the internal friction angle, which is consistent with the law of shear strength.

Abstract Cancer-associated fibroblasts (CAFs) contribute to tumour epithelial-mesenchymal transition (EMT) via interaction with cancer cells. However, the molecular mechanisms underlying tumour-promoting EMT of CAFs in lung adenocarcinoma (ADC) remain unclear. Here, we observed that CAFs isolated from lung ADC promoted EMT via production of stromal cell-derived factor-1 (SDF-1) in conditioned medium (CM). CAF-derived SDF-1 enhanced invasiveness and EMT by upregulating CXCR4, β-catenin, and PPARδ, while downregulating these proteins reversed the effect. Furthermore, RNAi-mediated CXCR4 knockdown suppressed β-catenin and PPARδ expression, while β-catenin inhibition effectively downregulated PPARδ without affecting CXCR4; however, treatment with a PPARδ inhibitor did not inhibit CXCR4 or β-catenin expression. Additionally, pairwise analysis revealed that high expression of CXCR4, β-catenin, and PPARδ correlated positively with 75 human lung adenocarcinoma tissues, which was predictive of poor prognosis. Thus, targeting the CAF-derived, SDF-1-mediated CXCR4 β-catenin/ PPARδ cascade may serve as an effective targeted approach for lung cancer treatment.

Over the years, probabilistic nature of renewable energy sources (RES) and its influence on power system adequacy have been well studied. However, rather less attention has been paid to the impact of RES unit itself's and its power conversion system's (PCS') reliability, as well as their various connection topologies. This paper devises a comprehensive sensitivity study on how each of these elements can affect overall generating system reliability. given the plethora of RES configurations and components, it is of import to identify the most vulnerable element in RES. In this work, component importance is extended, for the first time, to generating capacity adequacy assessment (HLI). Measurement index is the centerpiece in reliability importance. New indices have to be introduced to facilitate the study. While the physical meaning of previously developed indices is lost, in this study indices are proposed based on traditional importance measures, of which the physical meaning are strictly retained and consistent with the definitions. With the proposed assessment technique, components in various RES configuration can be ranked according to their reliability importance. It is found in the numerical study that different importance measures (such as risk-achievement based measures and risk-reduction based measures) can result in different rankings. Studies on contributing factors of the reliability importance are also performed. As more and more RES gaining foothold in generating systems, the proposed technique assist to achieve targeted reliability level of the system, by easily identifying and prioritizing reliability improvement tasks among various units/components in the increasing complex system.

Abstract Background Human umbilical cord mesenchymal stem cells (HUC-MSCs) present in the umbilical cord tissue are self-renewing and multipotent. They can renew themselves continuously and, under certain conditions, differentiate into one or more cell types constituting human tissues and organs. HUC-MSCs differentiate, among others, into osteoblasts, chondrocytes, and adipocytes and have the ability to secrete cytokines. The possibility of noninvasive harvesting and low immunogenicity of HUC-MSCs give them a unique advantage in clinical applications. In recent years, HUC-MSCs have been widely used in clinical practice, and some progress has been made in their use for therapeutic purposes. Main body This article describes two aspects of the clinical therapeutic effects of HUC-MSCs. On the one hand, it explains the benefits and mechanisms of HUC-MSC treatment in various diseases. On the other hand, it summarizes the results of basic research on HUC-MSCs related to clinical applications. The first part of this review highlights several functions of HUC-MSCs that are critical for their therapeutic properties: differentiation into terminal cells, immune regulation, paracrine effects, anti-inflammatory effects, anti-fibrotic effects, and regulating non-coding RNA. These characteristics of HUC-MSCs are discussed in the context of diabetes and its complications, liver disease, systemic lupus erythematosus, arthritis, brain injury and cerebrovascular diseases, heart diseases, spinal cord injury, respiratory diseases, viral infections, and other diseases. The second part emphasizes the need to establish an HUC-MSC cell bank, discusses tumorigenicity of HUC-MSCs and the characteristics of different in vitro generations of these cells in the treatment of diseases, and provides technical and theoretical support for the clinical applications of HUC-MSCs. Conclusion HUC-MSCs can treat a variety of diseases clinically and have achieved good therapeutic effects, and the development of HUC-MSC assistive technology has laid the foundation for its clinical application.

Abstract Background Hypothermic ischemia-reperfusion arrhythmia remains the main factor affecting cardiac resuscitation under cardiopulmonary bypass. Existing research shows that certain miRNAs exhibit significantly different expressions and effects in arrhythmias, however, the effect of miRNAs on the progression of hypothermic ischemic–reperfusion arrhythmias (RA) and its potential mechanism remain to be further explored. Methods Sprague-Dawley (SD) rats were randomly divided into two groups (n = 8): a normal control group (Group C) and a hypothermic ischemia-reperfusion group (Group IR), which were used to establish a Langendorff isolated cardiac perfusion model. According to the arrhythmia scoring system, rats in group IR were divided into a high-risk group (IR-H) and a low-risk group (IR-L). miRNAs expression profiles of ventricular myocardium with global hypothermic ischemia–reperfusion and those of ventricular myocardium with hypothermic ischemia–RA were established through high-throughput sequencing. Furthermore, the aberrantly expressed miRNAs in myocardium with and without hypothermic ischemia–RA were screened and verified. The target genes of these aberrantly expressed miRNAs were predicted using RNAhybrid and MiRanda software. Based on Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, we determined the mRNA targets associated with these miRNAs and studied the miRNA–mRNA interaction during the cardiovascular disease progression. The aberrantly expressed miRNAs related to hypothermic ischemia–RA were validated by Real-time Quantitative polymerase chain reaction (RT-qPCR). Results Eight significantly aberrantly expressed miRNAs (rno-miR-122-5p, rno-miR-429, novel_miR-1, novel_miR-16, novel_miR-17, novel_miR-19, novel_miR-30, and novel_miR-43) were identified, among which six were up-regulated and two were down-regulated. Moreover, target genes and signaling pathways associated with these aberrantly expressed miRNAs were predicted and analyzed. The miRNA–mRNA interaction network graph showed that GJA1 gene was considered as the target of novel_miR-17. Conclusions Aberrantly expressed miRNAs were possibly associated with the formation mechanism of hypothermic ischemia–RA. Specific miRNAs, such as novel_miR-17 and rno-miR-429 are probably new potential targets for further functional studies of hypothermic ischemia–RA.

Scavenger receptor-A (SR-A) is mostly expressed by myeloid cells and has been attributed a variety of biological functions. Here the authors assess SR-A as a biomarker for diagnosis of rheumatoid arthritis (RA) using large-scale training and validation cohorts and show that modulating SR-A levels can alter progression of collagen-induced arthritis in mice.

Fast neutron computed tomography (FNCT) generally needs a longer measurement time because of low source strength and low detection efficiency. In order to reduce measurement time, methods of reducing single measurement time and the numbers of projection are employed, but, the two reductions lead to high statistics noise projections and sparse sampling. A good reconstruction algorithm can reduce the influence of these problems for reconstructed images. In this study, the maximum likelihood-expectation maximization algorithm (MLEM) based on the total variation algorithm (TV) and median root prior algorithm (MRP), named MLEM-TV-MRP has been proposed. The proposal incorporates the assumption of the Poisson distribution of projection noises, gradient image sparseness, and locally monotonous. The use of MLEM in the proposal was for reducing the influence of high statistics noise by considering the statistical characteristics of projection noise; the TV algorithm was employed to decrease the influence of sparse sampling by considering gradient image sparseness. Also, the MRP was introduced to remove artifacts and noise by considering the locally monotonous. In addition, a consistency-controlled steepest descent (CCSD) method and TV change method were respectively employed to adaptively adjust the iteration step-size of TV iteration and adaptively stop TV iteration in the proposed algorithm. A classical noise-free phantom was used to initially test the performance of the proposed algorithm- the results showed high-quality reconstruction. To further illustrate its performance in FNCT, a lead-polyethylene (Pb-CH2) sample with 25 high statistics noise projections was employed. SNR value of MLEM-TV-MRP showed an increase of about 62%, 40.7%, 36.7%, and 12.6% respectively as compared to the single-use of MLEM, MLEM-MRP, TV-POCS (projection on convex sets) and MLEM-TV. Also, the profile of the MLEM-TV-MRP algorithm is found to be closest to that of a reference image. In addition, the MLEM-TV-MRP has good convergence performance especlially in convergence value. The results have demonstrated that the proposed algorithm can greatly reduce the influences of few high statistical noise projections on reconstruction in FNCT.

Objective We examined the accuracy of data from an affordable personal monitor (Fitbit Flex) compared with that of data from a research‐grade accelerometer worn simultaneously for 7 days; high accuracy would support substitution with this less‐expensive personal activity monitor in future community‐based arthritis research. Methods Subjects (N = 35) with chronic knee symptoms were recruited for a pilot intervention study using Fitbits to increase physical activity in employees with chronic knee symptoms at an urban corporation. Subjects simultaneously wore for 7 days a Fitbit Flex (wrist‐worn) and ActiGraph GT3X+ (waist‐worn). Fitbit Flex data were regularly stored on a research storage service (Fitabase) by participants. Bland–Altman plots were constructed to examine the agreement between the mean daily times spent in light activity and in bouted moderate‐to‐vigorous physical activity (MVPA). Comparisons were calculated by matching Fitabase data from calendar days the Fitbit was worn with data from valid monitoring days (greater than or equal to 10 hours wear time) of the ActiGraph. Results Participants at baseline were mostly female (69%) and white (57%) and had a mean age of 52 years and body mass index of 32 kg/m2. Bland–Altman analyses indicated systematic bias overall (the Fitbit overestimated both light‐intensity activity and MVPA compared with the ActiGraph). The average error varied in magnitude and direction with changing activity amounts. Conclusion The Fitbit Flex does not appear to be an adequate substitute for research‐grade accelerometry (which represents the gold standard for objective research monitoring of all physical activity intensity levels) in this population of persons with chronic knee symptoms.

TIGIT (T-cell immunoglobulin and ITIM domain) has emerged as a promising target in cancer immunotherapy. It is an immune “checkpoint” inhibitor primarily expressed on activated T cells, NK cells and Tregs. Engagement of TIGIT to its ligands PVR and PVR-L2 leads to inhibitory signaling in T cells, promoting functional exhaustion of tumor-infiltrating T lymphocytes. Here, we described the pre-clinical characterization of Ociperlimab (BGB-A1217), a novel humanized IgG1 anti-TIGIT antibody (mAb), and systemically evaluated the contribution of Fc functions in the TIGIT mAb-mediated anti-tumor activities. BGB-A1217 binds to the extracellular domain of human TIGIT with high affinity (KD = 0.135 nM) and specificity, and efficiently blocks the interaction between TIGIT and its ligands PVR or PVR-L2. Cell-based assays show that BGB-A1217 significantly enhances T-cell functions. In addition, BGB-A1217 induces antibody dependent cellular cytotoxicity (ADCC) against Treg cells, activates NK cells and monocytes, and removes TIGIT from T cell surfaces in an Fc-dependent manner, In vivo, BGB-A1217, either alone or in combination with an anti-PD-1 mAb elicits strong immune responses and potent anti-tumor efficacy in pre-clinical models. Moreover, the Fc effector function is critical for the anti-tumor activity of BGB-A1217 in a syngeneic human TIGIT-knock-in mouse model. The observed anti-tumor efficacy is associated with a pharmacodynamic change of TIGIT down-regulation and Treg reduction. These data support the selection of BGB-A1217 with an effector function competent Fc region for clinical development for the treatment of human cancers.

ABSTRACT Next-generation sequencing (NGS) enables rapid identification of common and rare drug-resistant genetic variations from tuberculosis (TB) patients’ sputum samples and MTB isolates. However, whether this technology is effective for formalin-fixed and paraffin-embedded (FFPE) tissues remains unclear. An amplicon-based targeted NGS sequencing panel was developed to predict susceptibility to 9 antituberculosis drugs, including 3 first-line drugs, by directly detecting FFPE tissues. A total of 178 tissue samples from TB patients who underwent phenotypic drug susceptibility test were retrospectively tested from January 2017 to October 2019 in the Department of Pathology, Beijing Chest Hospital, China. Phenotypic drug susceptibility test results were used as the reference standard. We identified 22 high-quality mutations from 178 FFPE tissue samples, including 15 high+moderate+minimal confidence-level mutations associated with drug resistance (rpoB D435V, S450F/L; KatG S315T; inhA-fabG promoter c-15t; embB G406S, M306V; rpsL K43R, K88R, rrs a1401g, a514c; gyrA D94G/Y/A, A90V), 6 mutations not associated with resistance (rpoB D435Y, H445S, L430P, L452P; embB G406A/D), and one mutation site embB M306I defined as indeterminate. Compared to the phenotypic method, sensitivities (95% CI) for rifampicin, isoniazid, and ethambutol were 96% (79.65–99.90%), 93.55% (78.58–99.21%), and 71.43% (35.24–92.44%), respectively; while for second-line drugs, it varied from 23.53% (9.05–47.77%) for capreomycin to 86.84% (72.20–94.72%) for streptomycin. Specificities for all drugs were satisfactory (>94.51%). Therefore, important pathological FFPE tissue samples, despite partially degraded DNA, can be used as essential specimens for molecular diagnosis of drug resistant TB by amplicon-based targeted NGS technology. IMPORTANCE Amplicon-based targeted NGS technology focuses on a set of gene mutations of known or suspected associations with drug susceptibility in Mycobacterium tuberculosis (MTB). This method offers many benefits, such as low sequencing cost, easy customization, high throughput, shorter testing time and not culture dependent. Formalin-fixed and paraffin-embedded (FFPE) tissues are important pathological specimen in diagnosing tuberculous disease because they are noninfectious and provide excellent preservation of tissue morphology with low storage cost. However, the performance of amplicon-based targeted NGS method on FFPE samples has not been reported yet. Therefore, we evaluated the performance of this method using FFPE samples collected from January 2017 to October 2019 in the Department of Pathology, Beijing Chest Hospital, China. We demonstrate that the amplicon-based targeted NGS method performs excellent on FFPE samples, and it can be applied to pathological diagnosis of drug resistant tuberculosis.

Objectives.The effect of insulin therapy on coronary artery disease (CAD) remains controversial. This study aimed to analyze the association between insulin resistance and the morbidity of severe CAD in type 2 diabetes mellitus (T2DM). Methods. A total of 2044 T2DM patients aged ≥40 years were included in this cross-sectional observational study. Clinical information and laboratory results were collected from the medical records. Those who underwent percutaneous coronary intervention (PCI) were classified as severe CAD, while those who did not have a history of and were not suffering from CAD were classified as patients without CAD. Results. T2DM patients with severe CAD and without CAD had no significant differences in glycosylated hemoglobin A1c (8.55% ± 2.10% vs. 8.39% ± 1.77%, P=0.234). The proportion of insulin treatment was also similar between the two groups (56.85% vs. 53.65%, odds ratio = 1.138, P=0.310). In the patients without insulin treatment, the levels of fasting C peptide (FCP) correlated with severe CAD prevalence. FCP was categorized into 3 tertiles (

Yttria-stabilized zirconia (YSZ) has been widely used in structural and functional ceramics because of its excellent physicochemical properties. In this paper, the density, average gain size, phase structure, and mechanical and electrical properties of conventionally sintered (CS) and two-step sintered (TSS) 5YSZ and 8YSZ are investigated in detail. As the grain size of YSZ ceramics became smaller, dense YSZ materials with a submicron grain size and low sintering temperature were optimized in terms of their mechanical and electrical properties. 5YSZ and 8YSZ in the TSS process significantly improved the plasticity, toughness, and electrical conductivity of the samples and significantly suppressed the rapid grain growth. The experimental results showed that the hardness of the samples was mainly affected by the volume density, that the maximum fracture toughness of 5YSZ increased from 3.514 MPa·m1/2 to 4.034 MPa·m1/2 in the TSS process, an increase of 14.8%, and that the maximum fracture toughness of 8YSZ increased from 1.491 MPa·m1/2 to 2.126 MPa·m1/2, an increase of 42.58%. The maximum total conductivity of the 5YSZ and 8YSZ samples under 680 °C increased from 3.52 × 10−3 S/cm and 6.09 × 10−3 S/cm to 4.52 × 10−3 S/cm and 7.87 × 10−3 S/cm, an increase of 28.41% and 29.22%, respectively.

The study of heterotrophic protists in the ocean is still in its early stages, compared to other microorganisms such as bacteria, archaea, and photoautotrophic protists. Labyrinthulomycetes protists (LP) are a type of unicellular protists that are widely distributed in global waters and have the potential to produce high-value products. In this study, the abundance, diversity, and community structure of LP in the coastal zone of Hainan Island in the South China Sea were investigated through quantitative PCR and high-throughput sequencing. The results showed that LP abundance varied by location and depth, with the highest levels (37.3 × 103 copies/L) found in the middle layer offshore and the lowest (0.386 × 103 copies/L) in the bottom layer offshore. The middle layer (chlorophyll maximum layer) had higher LP abundance both inshore and offshore than the surface and bottom layers. Interestingly, the highest LP richness and diversity was found in the inshore bottom. There was a significant difference in LP abundance between the offshore surface and bottom layers. The LP community was dominated by the genus Aplanochytrium, and four different ecotypes were identified. Additionally, the genus Aurantiochytrium had different cooperative and competitive strategies with bacteria in different habitats. This study sheds light on the abundance and community structure of LP in the coastal zone of Hainan Island, explores the potential interactions between LP and bacterial populations, and raises questions about the potential differentiation of LP ecotypes.

Transmembrane Channel-like (TMC) genes are critical in the carcinogenesis, proliferation, and cell cycle of human cancers. However, the multi-omics features of TMCs and their role in the prognosis and immunotherapeutic response of human cancer have not been explored. We discovered that TMCs 4-8 were commonly deregulated and correlated with patient survival in a variety of cancers. For example, TMC5 and TMC8 were correlated with the relapse and overall survival rates of breast cancer and skin melanoma, respectively. These results were validated by multiple independent cohorts. TMCs were regulated by DNA methylation and somatic alterations, such as TMC5 amplification in breast cancer (523/1062, 49.2%). Six algorithms concordantly uncovered the critical role of TMCs in the tumor microenvironment, potentially regulating immune cell toxicity and lymphocytes infiltration. Moreover, TMCs 4-8 were correlated with tumor mutation burden and expression of PD-1/PD-L1/CTLA4 in 33 cancers. Thus, we established an immunotherapy response prediction (IRP) score based on the signature of TMCs 4-8. Patients with higher IRP scores showed higher immunotherapeutic responses in five cohorts of skin melanoma (area under curve [AUC] = 0.90 in the training cohort, AUCs range from 0.70 to 0.83 in the validation cohorts). Together, our study highlights the great potential of TMCs as biomarkers for prognosis and immunotherapeutic response, which can pave the way for further investigation of the tumor-infiltrating mechanisms and therapeutic potentials of TMCs in cancer.