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Methyl 7,7′-dimethoxy-5′-(morpholinomethyl)-[4,4′-bibenzo[d][1,3] dioxole]-5-carboxylate methanesulfonate (IMM) is an innovative drug for the treatment of nonalcoholic fatty liver disease (NAFLD) owing to its high efficacy and low toxicity. In this study, five minor impurities (I, II, III, IV, and V) were identified and analyzed using spectroscopic evidence, chemical synthetic methods, and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The impurities included hydrolysates and oxidation by-products extracted from both the drug in its final formulation and during synthesis. Toxicity prediction revealed potential carcinogenicity of impurity V containing an N-oxygen fragment. A reliable and selective HPLC method for the quantitative analysis of impurities I–IV and a sensitive HPLC-MS/MS method for potential genotoxic impurity V were developed and optimized. The methods were validated based on the International Council for Harmonization guidelines. Satisfactory linearity was obtained for the analytes over the range of 0.1–2.0 μg/mL for impurities I–IV and 0.3–30.0 ng/mL for impurity V, and in all cases, the fitting correlation coefficients exceeded 0.999. The obtained limits of detection values were 0.05 ng/mL and 0.005 μg/mL for impurity V and impurities I–IV, respectively. The precision and repeatability of the methods were less than 1.08% and 8.72% for each impurity. The recovery percentages of all impurities were in the range of 91.18%–111.27%, with the relative standard deviation of less than 3.69%. The greenness assessment of the HPLC method and the HPLC-MS/MS method were evaluated by using AGREE software with a score value of 0.72 and 0.68, respectively. The recommended procedures that were accurate, specific, and ecofriendly were applied to the existing active pharmaceutical ingredients of IMM, and they generated satisfactory results.

Recently, ecological damage and environmental pollution have become increasingly serious. Experts in various fields have started to study related issues from diverse points of view. To prevent the accelerated deterioration of the ecological environment, ecolinguistics emerged. Eco-critical discourse analysis is one of the important parts of ecolinguistics research, that is, it is a critical discourse analysis of the use of language from the perspective of the language's ecological environment. Firstly, an ecological tone and modality system are constructed from an ecological perspective. Under the guidance of the ecological philosophy of "equality, harmony, and symbiosis", this study conducts an ecological discourse analysis on the Sino-US trade friction reports, aiming to present the similarities and differences between the two newspapers' trade friction discourses and to reveal the ecological significance of international ecological factors in the discourse. Secondly, this method establishes a vector expression of abstract words based on emotion dictionary resources and introduces emotion polarity and part-of-speech features of words. Then the word vector is formed into the text feature matrix, which is used as the input of the Convolutional Neural Network (CNN) model, and the Back Propagation algorithm is adopted to train the model. Finally, in the light of the trained CNN model, the unlabeled news is predicted, and the experimental results are analyzed. The results reveal that during the training process of Chinese and English datasets, the accuracy of the training set can reach nearly 100%, and the loss rate can be reduced to 0. On the test set, the classification accuracy of Chinese text can reach 83%, while that of English text can reach 90%, and the experimental results are ideal. This study provides an explanatory approach for ecological discourse analysis on the news reports of Sino-US trade frictions and has certain guiding significance for the comparative research on political news reports under different ideologies between China and the United States.

Cyclin-dependent kinases 4 and 6 (CDK4/6) are key regulatory proteins in the cell division and proliferative cycle in humans. They are overactive in many malignant tumors, particularly in triple-negative breast cancer (TNBC). Inhibition of CDK4/6 targets can have anti-tumor effects. Here, we designed and synthesized a novel derivative of Ribociclib that could affect CDK4/6, named WXJ-202. This study aimed to investigate the effects of compound WXJ-202 on proliferation, apoptosis, and cell cycle arrest in human breast cancer cell lines and their molecular mechanisms. We assayed cell viability with methyl thiazolyl tetrazolium (MTT) assay. Clone formation, migration, and invasion ability were assayed by clone formation assay, wound healing assay, and transwell invasion assay. The effect of compound WXJ-202 on apoptosis and cell cycle was detected by flow cytometry analysis. Western blotting was performed to detect the expression of proteins related to the CDK4/6-Rb-E2F pathway. The anti-cancer effects were studied in vivo transplantation tumor models. WXJ-202 was shown to inhibit cell proliferation, colony formation, migration, and invasion, as well as induce apoptosis and cycle arrest in breast cancer cells. The levels of proteins related to the CDK4/6-Rb-E2F pathway, such as CDK4, CDK6, and p-Rb, were decreased. Finally, studies had shown that compound WXJ-202 exhibited significant anti-tumor activity in transplantation tumor models. In this research, the compound WXJ-202 was shown to have better anti-tumor cell proliferative effects and could be used as a potential candidate against TNBC tumors.

The prevalence of soluble aluminum (Al) ions is one of the major limitations to crop production worldwide on acid soils. Therefore, understanding the Al tolerance mechanism of rice and applying Al tolerance functional genes in sensitive plants can significantly improve Al stress resistance. In this study, transcriptomics and metabolomics analyses were performed to reveal the mechanism of Al tolerance differences between two rice landraces (Al-tolerant genotype Shibanzhan (KR) and Al-sensitive genotype Hekedanuo (MR) with different Al tolerance. The results showed that DEG related to phenylpropanoid biosynthesis was highly enriched in KR and MR after Al stress, indicating that phenylpropanoid biosynthesis may be closely related to Al tolerance. E1.11.1.7 (peroxidase) was the most significant enzyme of phenylpropanoid biosynthesis in KR and MR under Al stress and is regulated by multiple genes. We further identified that two candidate genes Os02g0770800 and Os06g0521900 may be involved in the regulation of Al tolerance in rice. Our results not only reveal the resistance mechanism of rice to Al stress to some extent, but also provide a useful reference for the molecular mechanism of different effects of Al poisoning on plants.

AIM: To investigate the clinical features of adult patients with ocular toxocariasis (OT) in north China and to diagnose adults OT patients in early stage. METHODS: Clinical data of 24 adults with OT were retrospectively analyzed. Slit lamp photographs and fundus photographs and other imaging examinations of all the patients were reviewed. A questionnaire concerning the pet ownership and place of residence was completed to investigate the possible infection origin. Descriptive statistical analyses were performed on the demographic data, clinical features, funduscopic findings and ELISA results. RESULTS: Among the 24 patients diagnosed with OT by Toxocara IgG antibody in intraocular fluid, 16 (66.7%) eyes were right eye. The onset age of 12 eyes (50.0%) was between 30 and 40 years old, and 21 (87.5%) eyes were of peripheral granuloma type. The most common sign was vitreous opacity. Granulomas were detected in all the eyes, and 20 (83.3%) patients resided in rural area. In 4 patients, the concentration of anti-Toxocara antibody both in anterior humor and in vitreous humor were detected, and the results showed the concentration in vitreous humor was much higher than aqueous humor. CONCLUSION: Our study analyzes the clinical manifestation of OT in adults, which may have been under-recognized before. Eye side, residence, and detection of granuloma may help us in diagnosis of OT in patients with monocular vitreous opacity. For adult patients with presumed OT, negative results of anti-Toxocara antibody in anterior humor cannot rule out the possibility of OT, further detection of vitreous humor is suggested for final diagnosis.

Abstract Background Only when people feel they have received timely disclosure will they have sufficient incentive to implement community prevention and control measures. The timely and standardized information published by authorities as a response to the crisis can better inform the public and enable better preparations for the pandemic during the low transmission period of COVID-19; however, there is limited evidence of whether people consent that information is disclosed timely and influencing factors. Methods A cross-sectional survey was conducted in China from 4 to 26 February 2021. Convenient sampling strategy was adopted to recruit participators. Participants were asked to filled out the questions that assessed questionnaire on the residents’ attitudes to information disclosure timely. A binary logistic regression analysis was performed to identify the risk factors affecting the residents’ attitudes. Results A total of 2361 residents filled out the questionnaire. 1704 (72.17%) consented COVID-19 information has been disclosed timely. Furthermore, age (OR = 0.093, 95%CI = 0.043 ~ 0.201), gender (OR = 1.396, 95%CI = 1.085 ~ 1.797), place of residence (OR = 0.650, 95%CI = 0.525 ~ 0.804), employed status (OR = 2.757, 95%CI = 1.598 ~ 4.756), highest educational level (OR = 0.394, 95%CI = 0.176 ~ 0.880), region (OR = 0.561, 95%CI = 0.437 ~ 0.720) and impact on life by the COVID-19 (OR = 0.482, 95%CI = 0.270 ~ 0.861) were mainly factors associated with residents’ attitudes. Conclusions The aims of this study were to evaluate the residents attitudes to information disclosure timely during the low transmission period in China and to provide a scientific basis for effective information communication in future public health crises. Timely and effective efforts to disclose information need to been made during the low transmission period. Continued improvements to local authority reporting will contribute to more effective public communication and efficient public health research responses. The development of protocols and the standardization of epidemic message templates—as well as the use of uniform operating procedures to provide regular information updates—should be prioritized to ensure a coordinated national response.

Abstract Four high-entropy perovskite (HEP) RETa3O9 samples were fabricated via a spark plasma sintering (SPS) method, and the corresponding thermophysical properties and underlying mechanisms were investigated for environmental/thermal barrier coating (E/TBC) applications. The prepared samples maintained low thermal conductivity (1.50 W·m−1·K−1), high hardness (10 GPa), and an appropriate Young’s modulus (180 GPa), while the fracture toughness increased to 2.5 MPa·m1/2. Nanoindentation results showed the HEP ceramics had excellent mechanical properties and good component homogeneity. We analysed the influence of different parameters (the disorder parameters of the electronegativity, ionic radius, and atomic mass, as well as the tolerance factor) of A-site atoms on the thermal conductivity. Enhanced thermal expansion coefficients, combined with a high melting point and extraordinary phase stability, expanded the applications of the HEP RETa3O9. The results of this study had motivated a follow-up study on tantalate high-entropy ceramics with desirable properties.

Nonalcoholic steatohepatitis (NASH) is a chronic liver disease with complex disease mechanisms. Here the authors report that the E3 ubiquitin-protein ligase Trim31 mitigates development of NASH via inhibition of rhomboid 5 homolog 2 (Rhbdf2) in mice.

Therapeutic oligonucleotides (TOs) represent one of the most promising drug candidates in the targeted cancer treatment due to their high specificity and capability of modulating cellular pathways that are not readily druggable. However, efficiently delivering of TOs to cancer cellular targets is still the biggest challenge in promoting their clinical translations. Emerging as a significant drug delivery vector, nanoparticles (NPs) can not only protect TOs from nuclease degradation and enhance their tumor accumulation, but also can improve the cell uptake efficiency of TOs as well as the following endosomal escape to increase the therapeutic index. Furthermore, targeted and on-demand drug release of TOs can also be approached to minimize the risk of toxicity towards normal tissues using stimuli-responsive NPs. In the past decades, remarkable progresses have been made on the TOs delivery based on various NPs with specific purposes. In this review, we will first give a brief introduction on the basis of TOs as well as the action mechanisms of several typical TOs, and then describe the obstacles that prevent the clinical translation of TOs, followed by a comprehensive overview of the recent progresses on TOs delivery based on several various types of nanocarriers containing lipid-based nanoparticles, polymeric nanoparticles, gold nanoparticles, porous nanoparticles, DNA/RNA nanoassembly, extracellular vesicles, and imaging-guided drug delivery nanoparticles.

Abstract Background Physicians' depression can damage their physical and mental health and can also lead to prescribing errors and reduced quality of health care. Emergency physicians are a potentially high-risk community, but there have been no large-sample studies on the prevalence and predictors of depression among this population. Methods A nationally representative cross-sectional survey of 15,243 emergency physicians was conducted in 31 provinces across China between July and September 2019. Multivariable logistic regression analysis was performed to identify predictors of depression. Results A total of 35.59% of emergency physicians suffered from depression. Emergency physicians who were male (OR=0.91) and older [>37 and ≤43 (OR=0.83) or >43 (OR=0.71)], had high (OR=0.63) or middle (OR=0.70) level income, and participated in physical inactivity (OR=0.85) were not more likely to suffer depression. Meanwhile, those who were unmarried (OR=1.13) and smokers (OR=1.12) had higher education levels [Bachelor’s degree (OR=1.57) or Master’s degree or higher (OR=1.82)], long work tenure [>6 and ≤11 (OR=1.15) or >11;11 (OR=1.19)], poorer health status [fair (OR=1.67) or poor (OR=3.79)] and sleep quality [fair (OR=2.23) or poor (OR=4.94)], a history of hypertension (OR=1.13) and coronary heart disease (OR=1.57) and experienced shift work (OR=1.91) and violence (OR=4.94)]. Conclusion Nearly one third of emergency physicians in China suffered from depression. Targeted measures should be taken to reduce the prevalence of depression to avoid a decline in health care quality and adversely impact the supply of emergency medical services.

Objective: To identify the molecular mechanisms of the effects of the Buyin Qianzheng formula (BYQZF) on the mitochondrial dynamics in a Parkin overexpression Parkinson's disease (PD) cell model. Methods: First, a stable Parkin overexpression cell model was constructed using plasmid transfection. Then, we examined the protective effect of BYQZF on the mitochondrial dysfunction of the Parkin overexpression PD cell model induced by neurotoxin 1-methyl-4-phenylpyridinium ion (MPP+). The mRNA expression level of Parkin was evaluated using real-time quantitative PCR. The cell survival rate was detected using the Cell Counting Kit-8 assay. We evaluated the cellular adenosine triphosphate (ATP) levels using luciferase assays. A laser scanning confocal microscope was used to observe the mitochondrial morphology, activity, and mitochondrial membrane potential (ΔΨm). Western blot was conducted to evaluate the levels of the fusion proteins mitofusin1, mitofusin2, optic atrophy 1, dynamin-related protein 1, and mitochondrial fission protein 1. Results: Parkin overexpression attenuated MPP+ -induced mitochondrial damage, increased mitochondrial activity and ΔΨm. BYQZF increased the survival of MPP+-induced cells that overexpressed Parkin and upregulated the mitochondrial form factor and activity. It also inhibited a decrease in the ΔΨm and ATP levels. These findings suggested that BYQZF protected against MPP+-induced mitochondrial dysfunction and enhanced the protective effect of Parkin overexpression. Furthermore, the formula upregulated the expression of the fusion proteins mitofusin1, mitofusin2, and optic atrophy 1 (closely related to mitochondrial quality remodeling), and reduced the expression of the fission protein dynamic-related protein 1, as well as mitochondrial fission protein 1. Conclusion: The mechanism by which BYQZF increased the mitochondrial protective effect of Parkin gene overexpression in MPP+ -induced cells may be related to improving mitochondrial function and regulating the balance of mitochondrial division and fusion proteins.

Queries of youth orthopedic sports injuries from the U.S. National Electronic Surveillance System, a database from the Consumer Product Safety Commission, demonstrate decreased orthopedic injuries related to team sports during the COVID-19 pandemic, indicative of reduced sports participation. Multiple articles have shown that COVID-19 had a marked effect on the physical and psychological wellbeing of the youth. The lockdown resulted in a cessation in school attendance and sports activities, especially team sports. Though increased emphasis has been placed on children infected by COVID-19, less attention has been given to healthy children. Numerous articles discussed the physical and psychological benefits for the youth returning to physical activity and sports; however, few have addressed detraining and deconditioning concerns postpandemic. This article discusses a safe return to team sports for the youth experiencing physical and psychological changes related to the pandemic. Orthopedic injuries are anticipated to increase as restrictions are relaxed. A multidisciplinary team presents a review of common youth sports orthopedic injuries, a discussion of psychological issues youths have experienced during COVID and why sports participation is beneficial for youth, and a risk assessment for pain and limited range of motion for youth returning to sports. The intent of this article is to increase awareness of the physical and psychological changes experienced by youth due to their inability to participate in team sports during the pandemic. Family medicine and primary care providers need to recognize the increased risks for injury and proactively encourage the youth to return to sports in a safe manner.

Background: The Tibetan chicken has adapted well to high altitudes genetically after its long-term habitation in the plateau. In this study, we analyzed the selection signal of Tibetan black chickens (TBCs) and discovered genes associated with the characteristics of germplasm. Methods: Whole-genome sequencing (WGS) was used to identify the single-nucleotide polymorphism (SNP) markers and genetic structures in the genome of Tibetan black chickens. Further, we performed a comparative population genomics analysis between the genomic data obtained in this present study and the genomic data for five wild red jungle fowls (RJFs) accessed from the NCBI database (GenBank accession number PRJNA241474). Thereafter, the Fst and Pi selections were used to identify genes under positive selection in the Tibetan black chicken genome. Results: A total of 9,490,690 SNPs were identified in the Tibetan black chickens. In addition, the results from the gene ontology (GO) analysis showed that 732 genes of TBCs were enriched in a total of 210 GO terms with specific molecular functions such as regulation of cellular catabolic process, the MAPK signaling pathway, regulation of ion transport, growth, morphogenesis and lung alveolus development which may provide a better mechanism to facilitate oxygen transport and utilization in TBCs. Moreover, the results from the KEGG analysis showed that 732 genes of the TBCs were significantly enriched in the calcium signaling pathway, circadian entrainment (ADCY1, GNG7 and PER3), oxytocin signaling pathway and pathways of multiple neurodegeneration diseases. In addition, the CD86 antigen (CD86) was identified as a gene associated with the immune response in chickens. It was also revealed that genes such as TRIT1, HPCAL4, NT5C1A and HEYL were discovered under selection in Tibetan black chickens on chromosome 23. These genes may be related to the local adaptive characteristics of Tibetan black chickens, for instance, NT5C1A and HEYL may be involved in the high-altitude adaption of oxygen delivery in Tibetan black chickens. Conclusions: In summary, we found that selection mainly affects the disease resistance and cold acclimatization of Tibetan black chickens. Hence, these results may provide important genetic information for the evolution and breeding of Tibetan black chickens.

Polyaluminum chloride (PAC) is used widely and increasingly in wastewater treatment plants, resulting in its inevitably high production in sludge. Previous studies have indicated that the production of short-chain fatty acids (SCFAs) is inhibited by the existence of PAC in sludge anaerobic fermentation, so it is necessary to study how to promote sludge anaerobic fermentation under low concentrations of PAC. In this study, sodium citrate (SC) was first used to improve the efficiency of anaerobic fermentation under low concentrations of PAC. The results showed that the production of SCFAs increased with SC, especially when the ratio of PAC to SC was 1:2, and the maximum production of SCFAs reached 2890 mg/L, which is 2.5 times more than when PAC only exists. The mechanism studies showed that SC could remove the Al3+ in the sludge floc, which led to deflocculation of the sludge floc, accelerated the destruction of extracellular polymers (EPS), and released soluble substances in the sludge. At the same time, the key enzymes that were bound and hidden originally in the sludge were also released, which promoted the further degradation of organic matter and shortened the anaerobic fermentation period. However, the higher concentration of SC was not conducive to sludge dehydration. Therefore, the optimal distribution ratio of PAC to SC should be 1:1. This study provides a new idea for the research and practical application of sludge anaerobic fermentation.

This study aimed to develop extended-release tablets containing 25 mg IMM-H014, an original drug formulated by a direct powder pressing method based on pharmaceutical-grade hydrophilic matrix polymers such as hydroxypropyl methylcellulose, to establish an in vitro–in vivo correlation (IVIVC) to predict bioavailability. The tablets’ mechanical properties and in vitro and in vivo performance were studied. The formulation was optimized using a single-factor experiment and the reproducibility was confirmed. The in vitro dissolution profiles of the tablet were determined in five dissolution media, in which the drug released from the hydrophilic tablets followed the Ritger–Peppas model kinetics in 0.01 N HCl medium for the first 2 h, and in phosphate-buffered saline medium (pH 7.5) for a further 24 h. Accelerated stability studies (40 °C, 75% relative humidity) proved that the optimal formulation was stable for 6 months. The in vivo pharmacokinetics study in beagle dogs showed that compared to the IMM-H014 immediate release preparation, the maximum plasma concentration of the extended-release (ER) preparation was significantly decreased, while the maximum time to peak and mean residence time were significantly prolonged. The relative bioavailability was 97.9% based on the area under curve, indicating that the optimal formulation has an obvious ER profile, and a good IVIVC was established, which could be used to predict in vivo pharmacokinetics based on the formulation composition.

Holographic synthetic aperture radar tomography (HoloSAR) combines circular synthetic aperture radar (CSAR) and SAR tomography (TomoSAR) to enable a 360° azimuth observation of the considered scene. This imaging mode achieves a high-resolution three-dimensional (3-D) reconstruction across a full 360°. To capture the deformation information of the observed target, this paper first explores the differential HoloSAR imaging mode, which combines the technologies of CSAR and differential TomoSAR (D-TomoSAR). Then, we propose an imaging method based on the orthogonal matching pursuit (OMP) algorithm and a support generalized likelihood ratio (Sup-GLRT), aiming to achieve high-precision multi-dimensional reconstruction of the surveillance area. In addition, a statistical outlier removal (SOR) point cloud filtering technique is applied to enhance the accuracy of the reconstructed point cloud. Finally, this paper presents the detection of vehicle changes in a parking lot based on the 3-D reconstructed results.

The multi-task convolutional neural network (MTCNN) face detection algorithm has a low detection rate of small faces in classroom scenes. An improved MTCNN algorithm that integrates context features was thus proposed. Firstly, the context convolution module was integrated with the R-Net layer network of the MTCNN model, and the feature map receptive field was expanded to obtain more small face information. Secondly, the deconvolution layer and the max-pooling layer were introduced to solve the problem of inconsistency of feature fusion data dimensions. Finally, the O-Net layer network of the MTCNN model integrated the context convolution module to further extract the small face feature information, and two convolutional pooling layers were introduced for feature fusion. The experimental results show the detection accuracy increased by 3% on the FDDB data set, the face detection recall rate and the F1 score increased by 8.69% and 4.94% respectively on the classroom scene data set compared with those of MTCNN algorithm.

Postvaccination serologic testing (PVST) is utilized to monitor the success or failure of vaccination against hepatitis B virus (HBV) infection in infants of hepatitis B surface antigen (HBsAg) positive mothers. This secondary analysis of 1255 infants of HBsAg-positive mothers at 7–14 months age included in two prospective studies aimed to determine the optimal interval for PVST after three hepatitis B vaccine doses. HBsAg and anti-HBs were quantitatively tested with microparticle enzyme immunoassay. The average PVST interval was 3.8 ± 2.2 months. Overall, 1.7% (21/1255) infants had anti-HBs

The objectives of this study were to determine coronavirus disease 2019 (COVID-19) vaccination hesitancy and influencing factors in China, while broadening the applicability of the Vaccine Hesitancy Scale (VHS). A cross-sectional survey was conducted in China from 4th to 26th February 2021. Convenience sampling method was adopted to recruit participants. A total of 2,361 residents filled out the questionnaire. Confirmatory factor analysis was used on the validation set to confirm the latent structure that resulted from the exploratory factor analysis, which was conducted on the construction set. Multiple linear regression model analyses were used to identify significant associations between the identified the revised version of VHS subscales and hypothesized explanatory variables. Two subscales were identified within the VHS through data analysis, including “lack of confidence in the need for vaccines” and “aversion to the risk of side effects.” The results indicated that the hesitancy of the participants in our sample was both driven the two mainly aspects. In addition, more than 40% of the participants expressed hesitation in half of the items in VHS. This study characterized COVID-19 vaccine hesitancy in China, and identified disparities in vaccine hesitancy by socio-demographic groups and knowledge about the vaccine. Knowledge of the vaccine was statistically linked to respondents’ answers to the clustered ‘lack of confidence’ and ‘risks perception’ items. Our results characterize Chinese citizens’ COVID-19 vaccine concerns and will inform targeted health communications.

Objective: To reveal the mechanism of Mahuang Lianqiao Chixiaodou decoction and its disassembled formula for improving the skin barrier function in a mouse model of atopic dermatitis (AD). Methods: Sixty specific-pathogen free male BALB/c mice were randomly divided into the control group, model group, whole formula group (WF), exterior-releasing formula group (ERF), interior-clearing formula group (ICF), and positive control group (PC). A mouse model of AD was established using the semi-antigen 2,4-dinitrofluorobenzene induction method. The lesion scores, transepidermal water loss and pH, and skin histopathology of mice in each group were observed. The expressions of filaggrin, loricrin, and involucrin were detected by the streptavidin peroxidase immunohistochemical method and western blotting, and their mRNA expressions were detected by quantitative polymerase chain reaction. Results: Mice in the WF, ERF, ICF, and PC groups showed reduced skin lesion performance, improved histopathology, decreased skin lesion score, transepidermal water loss and pH, and upregulated expressions of proteins including filaggrin, loricrin, and involucrin, and their mRNAs. The most obvious regulatory effect was observed in the WF group, followed by the ICF, ERF, and PC groups, accordingly. Conclusions: Mahuang Lianqiao Chixiaodou decoction and its disassembled formula can improve the skin barrier function in a mouse model of AD by upregulating filaggrin, loricrin, and involucrin, and their mRNA expressions, and the most optimal effect was noted in the WF group, followed by the ICF and ERF groups, which suggests that the effect of clearing heat and resolving dampness in improving the skin barrier function of AD is more obvious and is one of the key treatments for AD.

Abstract Triple‐negative breast cancer (TNBC) is still the most aggressive cancer in women. Combination chemotherapy holds great potential for cancer therapy; however, the off‐target and side effects of free chemotherapy administration remain a major challenge. In this study, we developed a photo/thermo‐responsive nanoplatform that can be used for TNBC treatment via photothermic therapy in combination with multidrug therapy. By conjugating the chemotherapy drug PTX prodrug on the surface of mesoporous silica‐coated gold nanorod nanoparticles and then loading another chemotherapy drug, CPT, the Au@MSN‐PTX@CPT nanoparticles exhibited great photothermal response, redox response drug release and cancer cell inhibition abilities. Otherwise, we further coated the Au@MSN‐PTX@CPT nanoparticle with a temperature‐sensitive polymer poly(N‐isopropylacrylamide‐co‐methacrylic acid) (p(NIPAM‐co‐MAAc)), and the polymer‐coated Au@MSN‐PTX@TPT@polymer nanoparticles showed perfect near‐infrared (NIR) light controlled drug release. Finally, the Au@MSN‐PTX@CPT@polymer nanoparticles were injected into the 4T1 breast cancer mouse model. The Au@MSN‐PTX@CPT@polymer nanoparticles preferably accumulated at the tumor site and had reduced chemotherapy injuries and great antitumor activity when combined with 650 nm laser treatment. In summary, our developed Au@MSN‐PTX@CPT@polymer nanoparticles served as a good method for controlled chemodrug delivery and provided a good choice for TNBC combination therapy.

In the context of resource constraints, how different dimensions of entrepreneurial alertness affect the entrepreneurial opportunity recognition of new ventures is an important issue worth studying. From entrepreneurial cognition theory and bricolage theory perspectives, we systematically investigate the intrinsic relationships among entrepreneurial alertness, entrepreneurial bricolage, entrepreneurial passion, and entrepreneurial opportunity recognition. Further, it explored the intrinsic mechanism of role in exploring entrepreneurial opportunity recognition. This study applied stepwise regression analyses and the Bootstrap method to test the hypotheses on a sample of 295 questionnaires of the new venture. The findings revealed that entrepreneurial alertness is positively related to entrepreneurial opportunity recognition. Entrepreneurial bricolage is positively related to entrepreneurial opportunity recognition. Entrepreneurial bricolage partially mediates between entrepreneurial alertness and entrepreneurial opportunity recognition. Entrepreneurial passion positively moderates the relationship between entrepreneurial bricolage and entrepreneurial opportunity identification. The study guides new ventures to enhance entrepreneurial alertness and reasonably use entrepreneurial bricolage to explore entrepreneurial opportunities.

To defend against a vast variety of challenges in oxygenated environments, all life forms have evolutionally established a set of antioxidants, detoxification, and cytoprotective systems during natural selection and adaptive survival, to maintain cell redox homeostasis and organ integrity in the healthy development and growth. Such antioxidant defense systems are predominantly regulated by two key transcription factors Nrf1 and Nrf2, but the underlying mechanism(s) for their coordinated redox control remains elusive. Here, we found that loss of full-length Nrf1 led to a dramatic increase in reactive oxygen species (ROS) and oxidative damages in Nrf1α–∕– cells, and this increase was not eliminated by drastic elevation of Nrf2, even though the antioxidant systems were also substantially enhanced by hyperactive Nrf2. Further studies revealed that the increased ROS production in Nrf1α–∕– resulted from a striking impairment in the mitochondrial oxidative respiratory chain and its gene expression regulated by nuclear respiratory factors, called αPalNRF1 and GABPNRF2. In addition to the antioxidant capacity of cells, glycolysis was greatly augmented by aberrantly-elevated Nrf2, so to partially relieve the cellular energy demands, but aggravate its mitochondrial stress. The generation of ROS was also differentially regulated by Nrf1 and Nrf2 through miR-195 and/or mIR-497-mediated UCP2 pathway. Consequently, the epithelial-mesenchymal transformation (EMT) of Nrf1α–∕– cells was activated by putative ROS-stimulated signaling via MAPK, HIF1α, NF-ƙB, PI3K and AKT, all players involved in cancer development and progression. Taken together, it is inferable that Nrf1 acts as a potent integrator of redox regulation by multi-hierarchical networks.

Jasmine [Jasminum sambac (L.) Aiton] is a commercially important cultivated plant species known for its fragrant flowers used in the perfume industry, medicine and cosmetics. In the present study, we obtained a draft genome for the J. sambac cultivar ‘Danbanmoli’ (JSDB, a single-petal phenotype). We showed that the final genome of J. sambac was 520.80 Mb in size (contig N50 = 145.43 kb; scaffold N50 = 145.53 kb) and comprised 35,363 genes. Our analyses revealed that the J. sambac genome has undergone only an ancient whole-genome duplication (WGD) event. We estimated that the lineage that has given rise to J. sambac diverged from the lineage leading to Osmanthus fragrans and Olea europaea approximately 31.1 million years ago (Mya). On the basis of a combination of genomic and transcriptomic analyses, we identified 92 transcription factors (TFs) and 206 genes related to heat stress response. Base on a combination of genomic, transcriptomic and metabolomic analyses, a range of aroma compounds and genes involved in the benzenoid/phenylpropanoid and terpenoid biosynthesis pathways were identified. In the newly assembled J. sambac genome, we identified a total of 122 MYB, 122 bHLH and 69 WRKY genes. Our assembled J. sambac JSDB genome provides fundamental knowledge to study the molecular mechanism of heat stress tolerance, and improve jasmine flowers and dissect its fragrance.

Background: Previous studies have reported that the Toll-like receptors (TLRs) are related with the progress of chronic obstructive pulmonary disease (COPD). We aimed to explore the association of TLRs single nucleotide polymorphisms (SNPs) and COPD risk.Methods: 170 COPD patients and 181 healthy controls were enrolled in this case-control study. MassARRAY platform was used for genotyping seven tagging SNPs (TLR2: rs3804100, rs4696480, rs3804099; TLR3: rs3775290, rs3775291, rs5743305; TLR9: rs352140) of TLRs. The correlations between the SNPs and COPD risk were determined using logistic regression.Results: We found that the rs3775291 of TLR3 significant decreased the risk of COPD (TT versus CC: non-adjusted OR = 0.329, 95% CI = 0.123–0.879, p = 0.027). In the genetic models analysis, the rs3775291 was associated with a decreased effect of COPD based on the recessive model (TT versus CC/CT: non-adjusted OR = 0.377, 95% CI = 0.144–0.988 p = 0.047). The rs4696480 of TLR2 gene was associated with a decreased risk of COPD after adjustment by age and gender (TA versus AA: adjusted OR = 0.606, 95% CI = 0.376–0.975, p = 0.039).Conclusion: Our study showed that genetic variants in TLRs were associated with risk of COPD. The rs3775291 and rs4696480 may act as a potential biomarker for predicting the risk of COPD in Chinese population.

Advances in synthetic biology and the clinical application of bacteriotherapy enable the use of genetically engineered bacteria (GEB) to combat various diseases. GEB act as a small ‘machine factory’ in the intestine or other tissues to continuously produce heterologous proteins or molecular compounds and, thus, diagnose or cure disease or work as an adjuvant reagent for disease treatment by regulating the immune system. Although the achievements of GEBs in the treatment or adjuvant therapy of diseases are promising, the practical implementation of this new therapeutic modality remains a grand challenge, especially at the initial stage. In this review, we introduce the development of GEBs and their advantages in disease management, summarize the latest research advances in microbial genetic techniques, and discuss their administration routes, performance indicators and the limitations of GEBs used as platforms for disease management. We also present several examples of GEB applications in the treatment of cancers and metabolic diseases and further highlight their great potential for clinical application in the near future.

Background: Numerous clinical studies have shown that atopic dermatitis (AD) is often associated with mental disorders. This could contribute to the overall burden of atopic dermatitis. However, the underlying mechanism of mental health symptoms in AD has not been fully elucidated.Methods: An AD mouse was induced by 2,4-dinitrofluorobenzene (DNFB), which was repeatedly applied to the back skin of the BALB/C mice to establish an atopic dermatitis mental disorder model. The role of neuroinflammation in the pathogenesis of atopic dermatitis mental disorders was then explored.Results: After the stimulation of DNFB for 35 days, the skin lesions, the HE staining of skin lesions, and the behavioral experiments (including elevated plus maze assay and tail suspension test) suggested that the AD mental disorder mouse model was successfully replicated. The expression of neuroinflammatory factors in the hippocampus was then investigated through Western blotting. The results showed a significant increase in the protein expression of NLRP3, caspase-1, and IL-1β.Conclusion: Mental disorders in AD might be related to the neuroinflammatory response in the hippocampus. An alternative yet essential approach to promoting AD recovery could be through reducing neuroinflammation and improving mental disorders.

Abstract Background Congestive heart failure (CHF) is a major cause of the development of progressive chronic kidney disease (CKD), while the mechanism is still unknown. LncRNA PVT1 contributes to kidney injury. This study aimed to explore the role of PVT1 in the development of CKD in CHF patients. Methods Expression of PVT1 in plasma samples of CHF patients with and without CKD was determined by RT-qPCR. The diagnostic value of plasma PVT1 for CKD was evaluated by ROC curve analysis. The predictive value of PVT1 for the development of CKD in CHF patients was analyzed by a 2-year follow-up study. Changes in PVT1 expression in CKD patients during treatment were analyzed by RT-qPCR and reflected by heatmaps. Results Plasma PVT1 was downregulated in CHF and further downregulated in CHF patients complicated with progressive CKD. ROC curve analysis showed that plasma PVT1 levels could be used to distinguish CHF patients complicated with CKD from CHF patients without CKD and healthy controls. During a 2-year follow-up, patients with high CHF levels had a low incidence of progressive CKD among CHF patients. Moreover, with the treatment of progressive CKD, plasma PVT1 was upregulated. Conclusions LncRNA-PVT1 downregulation may participate in the development of progressive CKD among patients with CHF.

AIM: To understand retinopathy of prematurity (ROP) screening and treatment preferences among Chinese ophthalmologists. METHODS: A Chinese language survey was administered anonymously using WebQ (Catalyst, Seattle, WA, USA) among Chinese ROP screeners from December 2016 to January 2017. RESULTS: Among 70 ophthalmologists contacted, 65 responded (93%; 78% female, mean age 40y, 57% pediatric ophthalmologists and 25% retina specialists). Most used screening criteria of birth weight ≤2 kg (62%) with variation in cut-off gestational age (≤37wk, 34%; ≤34wk, 22%; ≤32wk, 31%). RetCam (Natus Medical Incorporated, Pleasanton, CA, USA) wide-field fundus photography assisted most screeners (72%) and was exclusively used by many (29%). Among 55 ophthalmologists treating ROP, anti-vascular endothelial growth factor (VEGF) was preferred over laser for both zone I (76% vs 24%) and zone II ROP (58% vs 42%). Retina specialists (P=0.004) and ophthalmologists with >3mo of training (P=0.03) were more likely to use anti-VEGF over laser for zone I ROP. Lack of laser training (8/20, 40%), access (6/20, 30%) and anesthesia (4/20, 20%) were common barriers to laser treatment. CONCLUSION: Chinese ROP screeners favor anti-VEGF injection and RetCam imaging for ROP management. A better understanding of ROP screening and treatment informs future research and education efforts in China.

We report a feasible method to realize tunable surface plasmon-polariton (SPP) resonance in organic light-emitting devices (OLEDs) by employing corrugated Ag-Al alloy electrodes. The excited SPP resonance induced by the periodic corrugations can be precisely tuned based on the composition ratios of the Ag-Al alloy electrodes. With an appropriate composition ratio of the corrugated alloy electrode, the photons trapped in SPP modes are recovered and extracted effectively. The 25% increasement in luminance and 21% enhancement in current efficiency have been achieved by using the corrugated Ag-Al alloy electrodes in OLEDs.

ABSTRACT: Fatty liver hemorrhagic syndrome (FLHS) is a chronic hepatic disease which occurs when there is a disorder in lipid metabolism. FLHS is often observed in caged laying hens and characterized by a decrease in egg production and dramatic increase of mortality. Salidroside (SDS) is an herbal drug which has shown numerous pharmacological activities, such as protecting mitochondrial function, attenuating cell apoptosis and inflammation, and promoting antioxidant defense system. We aimed to determine the therapeutic effects of SDS on FLHS in laying hens and investigate the underlying mechanisms through which SDS operates these functions. We constructed oleic acid (OA)-induced fatty liver model in vitro and high-fat diet-induced FLHS of laying hens in vivo. The results indicated that SDS inhibited OA-induced lipid accumulation in chicken primary hepatocytes, increased hepatocyte activity, elevated the mRNA expression of proliferation related genes PCNA, CDK2, and cyclinD1 and increased the protein levels of PCNA and CDK2 (P < 0.05), as well as decreased the cleavage levels of Caspase-9, Caspase-8, and Caspase-3 and apoptosis in hepatocytes (P < 0.05). Moreover, SDS promoted the phosphorylation levels of PDK1, AKT, and Gsk3-β, while inhibited the PI3K inhibitor (P < 0.05). Additionally, we found that high-fat diet-induced FLHS hens had heavier body weight, liver weight, and abdominal fat weight, and severe steatosis in histology, compared with the control group (Con). However, hens fed with SDS maintained lighter body weight, liver weight, and abdominal fat weight, as well as normal liver without hepatic steatosis. In addition, high-fat diet-induced FLHS hens had high levels of serum total cholesterol (TC), triglyceride (TG), alanine transaminase (ALT), and aspartate aminotransferase (AST) compared to the Con group, however, in the Model+SDS group, the levels of TC, TG, ALT, and AST decreased significantly, whereas the level of superoxide dismutase (SOD) increased significantly (P < 0.05). We also found that SDS significantly decreased the mRNA expression abundance of PPARγ, SCD, and FAS in the liver, as well as increased levels of PPARα and MTTP, and decreased the mRNA expression of TNF-α, IL-1β, IL-6, and IL-8 in the Model+SDS group (P < 0.05). In summary, this study showed that 0.3 mg/mL SDS attenuated ROS generation, inhibited lipid accumulation and hepatocyte apoptosis, and promoted hepatocyte proliferation by targeting the PI3K/AKT/Gsk3-β pathway in OA-induced fatty liver model in vitro, and 20 mg/kg SDS alleviated high-fat-diet-induced hepatic steatosis, oxidative stress, and inflammatory response in laying hens in vivo.

Deep learning evolves into a new form of machine learning technology that is classified under artificial intelligence (AI), which has substantial potential for large-scale healthcare screening and may allow the determination of the most appropriate specific treatment for individual patients. Recent developments in diagnostic technologies facilitated studies on retinal conditions and ocular disease in metabolism and endocrinology. Globally, diabetic retinopathy (DR) is regarded as a major cause of vision loss. Deep learning systems are effective and accurate in the detection of DR from digital fundus photographs or optical coherence tomography. Thus, using AI techniques, systems with high accuracy and efficiency can be developed for diagnosing and screening DR at an early stage and without the resources that are only accessible in special clinics. Deep learning enables early diagnosis with high specificity and sensitivity, which makes decisions based on minimally handcrafted features paving the way for personalized DR progression real-time monitoring and in-time ophthalmic or endocrine therapies. This review will discuss cutting-edge AI algorithms, the automated detecting systems of DR stage grading and feature segmentation, the prediction of DR outcomes and therapeutics, and the ophthalmic indications of other systemic diseases revealed by AI.

Spotted fever group (SFG) rickettsioses are important zoonoses, threatening human health seriously and gradually attracting more attention in the world. SFG rickettsiae are classified as neglected pathogens. If these pathogens are detected at all, they are usually recognized very late in the infection through indirect detection of specific antibodies. Previous studies have shown that Rickettsia raoultii (R. raoultii), a member of the SFG rickettsiae, occurs with increasing incidence in remote countries. Therefore, a rapid detection method for R. raoultii is in urgently need. In this study, a R. raoultii diagnosis method by closed dumbbell-mediated isothermal amplification (R-CDA) assay targeting a conserved sequence of the outer membrane protein A (OmpA) gene with high sensitivity and specificity was developed. This assay offered a rapid and simple method for on-site detection of R. raoultii. Firstly, four pairs of R-CDA primers were designed and the optimum primer set was selected to amplify target gene specifically and effectively. Then, a pair of outer primer was designed to accelerate the reaction based on the inner primers to establish the RO-CDA reaction. In addition, the results of real-time amplification curves, melting curves and end-point colorimetric judgements showed that the established visual RO-CDA reaction could accurately detect R. raoultii without cross-reaction with other closely related pathogens. Furthermore, the detection limit of visual RO-CDA assay was 10 copies/μL, which was feasible for on-site detection with merits of easy-operation, rapidity, high sensitivity, and specificity. In conclusion, the developed RO-CDA detection method could be helpful for pathogen screening and epidemic prevention at the point of care.

ObjectiveTo investigate the relations of Triglyceride glucose (TyG) index with cerebral small vessel disease (CSVD) burden and cognitive function in aged patients with type 2 diabetes mellitus (T2DM).MethodsA total of 308 elderly patients with T2DM were included in this retrospective study. The standardized Chinese version of Mini-Mental State Examination was used to assess cognitive function. The total CSVD burden score was assessed by combining four imaging markers of CSVD, including the presence of white matter hyperintensity, cerebral microbleeds in the deep, lacunes and enlarged perivascular spaces in the basal ganglia. The TyG index was calculated as the formula of ln [fasting triglyceride (mg/dl) × fasting plasma glucose (mg/dl)/2]. We used logistic regression analysis and mediation analysis to investigate the relations of TyG index with CSVD and cognitive function.ResultsMultivariate binary logistic regression analysis showed that increased TyG index (OR: 2.241; 95% Confidence Interval(CI): 1.439 to 3.490; P

Objectives: We aim to find out the prevalence, characteristics, and predictors of workplace violence (WPV) against current Chinese emergency department (ED) nurses.Methods: A cross-sectional survey of 20,136 ED nurses was conducted in 31 provinces in China between July and September 2019. Descriptive analyses were used to examine the prevalence and characteristics of WPV. Chi-square analysis and Binary logistic regression analysis were used to identify the predictors of WPV.Results: During the past 12 months, there are 79.39% of ED nurses exposed to any type of WPV, including 78.38% and 39.65% exposed to nonphysical and physical violence, respectively. Binary logistic regression analysis shows that ED nurses who were male, had bachelor’s degrees, had average monthly salary between 5,001 and 12,000, worked in central China, had higher professional titles, were more experienced, arranging shift work, and had higher work stress were more likely to experience WPV.Conclusion: A relatively high prevalence of WPV against Chinese ED nurses has been revealed in this study. The characteristics and predictors of WPV remind us to take positive measures to reduce WPV.

Background and AimsOral xerostomia remains one of the most common complications of differentiated thyroid carcinoma patients (DTC) after radioiodine therapy (RAI). Environmental factors in the etiology of xerostomia are largely unknown. We aimed to characterize the oral microbiota signatures and related biological functions associated with xerostomia and identify environmental factors affecting them.MethodsSaliva was collected from 30 DTC patients with xerostomia (XAs), 32 patients without xerostomia (indicated as non-XAs) following RAI after total thyroidectomy, and 40 healthy people (HCs) for 16S rRNA sequencing analysis.ResultsThe oral microbiota of XAs and non-XAs exhibited significant differences in α and β diversities and bacterial taxa. The abundance of porphyromonas, fusobacterium, and treponema_2 were significantly higher in XAs, while the abundance of the streptococcus was lower in the microbiota of non-XAs. Fusobacterium, and porphyromonas were negatively correlated with unstimulated/stimulated whole salivary secretion (USW)/(SWS), while fusobacterium, porphyromonas, and treponema_2 genera levels were positively associated with cumulative radioiodine dose. PICRUSt2 and BugBase suggested a significant difference in the expression of potentially_pathogenic, anaerobic, gram_negative, the arachidonic acid metabolism, and lipopolysaccharide (LPS) biosynthesis between XAs and non-XAs, possibly interdependent on radioiodine-induced inflammation. NetShift analysis revealed that porphyromonas genus might play as a key driver during the process of xerostomia. Five genera effectively distinguished XAs from non-XAs (AUC = 0.87).ConclusionOur study suggests for the first time that DTC patients with xerostomia after RAI display microbiota profiles and associated functional changes that may promote a pro-inflammatory environment. Dysbiosis of the oral microbiota may contribute to exacerbating the severity of xerostomia. Our results provide a research direction of the interaction mechanism between oral microbiota alteration and the progress of xerostomia.

ABSTRACT Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is a crucial disease for wheat worldwide and constantly threatens wheat production in southwestern and northwestern China, where the environment is a good fit for Pst oversummering and overwintering. However, the underlying genetic dynamics of spring epidemic Pst populations across large areas of continuous planting in the southwestern and northwestern regions are poorly understood. A total of 2,103 Pst isolates were sampled in the spring of 2019 from the two agroecosystems and grouped into three horizontal spatial scales (countywide, provincial, and regional subpopulations) and two vertical spatial scales that consisted of elevational and geomorphic subpopulations. A total of 776 multilocus genotypes were identified, with the highest genetic diversity found in the northern and Sichuan populations, particularly in the Ningxia and Sichuan Basins, while the lowest genetic diversity was found in the Yunnan and Guizhou populations. Multivariate discriminant analysis of principal components (DAPC) and STRUCTURE (STRUCTURE 2.3.4) analyses revealed variation in the genotypic compositions of the molecular groups on horizontal and vertical dimensions from north to south or vice versa and from low to high or vice versa, respectively. The regional neighbor-joining tree revealed three large spatial structures consisting of the southwestern, the northwestern, and the Xinjiang regions, while the Tibetan population connected the southwestern and northwestern regions. The isolates of the Sichuan Basin were scattered over the four quartiles by principal coordinate analysis, which indicated frequent genotype interchange with others. Greater genetic differentiation was observed between the southwestern and northwestern regions. Linkage equilibrium (P ≥ 0.05) was detected on different spatial scales, suggesting that Pst populations are using sexual reproduction or mixed reproduction (sexual and clonal reproduction) in southwestern and northwestern China. IMPORTANCE Understanding the epidemiology and population genetics of plant pathogens is crucial to formulate efficient predictions of disease outbreaks and achieve sustainable integrated disease management, especially for pathogens with migratory capability. Here, this study covers the genetic homogeneity and heterogeneity of different geographical Pst populations on broad to fine spatial scales from the key epidemic regions of the two agroecosystems in China, where wheat stripe rust occurs annually. We provide knowledge of the population genetics of Pst and reveal that, for instance, there is greater genetic diversity in northwestern China, there are close genetic relationships between Yunnan and Guizhou and between Gansu-Ningxia and Qinghai, and there are effects of altitude on genetic compositions, etc. All of these findings clarify the genetic relationships and expand the insights into the population dynamics and evolutionary mechanisms of Pst in southwestern and northwestern China, providing a theoretical basis for achieving sustainable control of wheat stripe rust in key epidemic regions.

The current study proposes a green synthesis method for silver nanoparticles (Ag NPs) using various concentrations of Flos Sophorae Immaturus extract as reducing and capping agents. The UV-Visible (UV-Vis) spectroscopy, X-ray Diffraction (XRD), Fourier Transform Infrared spectroscopy (FTIR), X-ray Photoelectron Spectroscopy (XPS), Dynamic Light Scattering (DLS) and Transmission Electron Microscopy (TEM) were used to characterize resulting brown nanopowder. The as-prepared Ag NPs had a high negative zeta potential value of ∼ -38 mv, indicating the existence of electrostatic stabilization. The average sizes of ∼27.8 nm, 28.5 nm, 34.3 nm and 36.5 nm were measured by TEM. Moreover, FTIR and XPS analyses validated the production and chemical composition of Ag NPs from silver nitrate. The antibacterial activity of Ag NPs was examined against E. coli, P. aeruginosa, and S. aureus using agar well diffusion and the minimum inhibitory concentration (MIC) method. The antibacterial activity of the as-prepared Ag NPs from 4 mL extract was excellent against E. coli, P. aeruginosa, and S. aureus and the MIC values were 31.250, 15.625, and 31.250 mg/L, respectively. Based on these results, this study proposes a practical approach for the synthesis of Ag NPs in the industry and medical fields.

In this study, we explored the clinical value of next-generation metagenome sequencing (mNGS) using bronchoalveolar lavage fluid (BALF) samples from patients with acid-fast staining (AFS) sputum smear-negative pulmonary tuberculosis (PTB) and non-tuberculous mycobacterial pulmonary disease (NTM-PD). Data corresponding to hospitalized patients with pulmonary infection admitted to the hospital between July 2018 and July 2021, who were finally diagnosed with AFS sputum smear-negative PTB and NTM-PD, were retrospectively analyzed. Bronchoscopy data as well as mNGS, Xpert, AFS (BALF analysis), and T-SPOT (blood) data, were extracted from medical records. Thereafter, the diagnostic performances of these methods with respect to PTB and NTM-PD were compared. Seventy-one patients with PTB and 23 with NTM-PD were included in the study. The sensitivities of mNGS, Xpert, T-SPOT, and AFS for the diagnosis of PTB were 94.4% (67/71), 85.9% (61/71), 64.8% (46/71), and 28.2% (20/71), respectively, and the diagnostic sensitivity of mNGS combined with Xpert was the highest (97.2%, 67/71). The specificity of Xpert was 100%, while those of AFS and T-SPOT were 73.9% (17/23) and 91.3% (21/23), respectively. Further, the 23 patients with NTM-PD could be identified using mNGS, and in the population with immunosuppression, the sensitivities of mNGS, Xpert, T-SPOT, and AFS were 93.5% (29/31), 80.6% (25/31), 48.4% (15/31), and 32.3% (10/31), respectively, and the diagnostic sensitivity of mNGS combined with Xpert was the highest (100%, 31/31). The specificities of Xpert and T-SPOT in this regard were both 100%, while that of AFS was 40% (2/5). Furthermore, using mNGS, all the NTM samples could be identified. Thus, the analysis of BALF samples using mNGS has a high accuracy in the differential diagnosis of MTB and NTM. Further, mNGS combined with Xpert can improve the detection of MTB, especially in AFS sputum smear-negative samples from patients with compromised immune states or poor responses to empirical antibiotics.

Abstract DNA nanomachines with artificial intelligence have attracted great interest, which may open a new era of precision medicine. However, their in vivo behavior, including early diagnosis and therapeutic effect are limited by their targeting efficiency. Here, a tetrahedral DNA framework (TDF)‐based nanodevice for in vivo near‐infrared (NIR) diagnosis of early‐stage AKI is developed. This nanodevice comprises three functional modules: a size‐tunable TDF nanostructure as kidney‐targeting vehicle, a binding module for the biomarker kidney injury molecule‐1 (Kim‐1), and a NIR signaling module. The cooperation of these modules allows the nanodevice to be selectively accumulated in injured kidney tissues with high Kim‐1 level, generating strong NIR fluorescence; whereas the nanodevice with the proper size can be rapidly cleared in healthy kidneys to minimize the background. By using this nanodevice, the early diagnosis of AKI onset is demonstrated at least 6 h ahead of Kim‐1 urinalysis, or 12 h ahead of blood detection. It is envisioned that this TDF‐based nanodevice may have implications for the early diagnosis of AKI and other kidney diseases.

ObjectiveTo investigate the relations of serum total homocysteine (tHcy) with cerebral small vessel disease (CSVD) and cognitive function and evaluate whether CSVD mediates the effect of serum tHcy on cognitive function.MethodsA total of 1,033 consecutive eligible participants who received serum tHcy, brain magnetic resonance imaging (MRI), and neuropsychological assessment were included in this retrospective study. White matter hyperintensity, lacune, cerebral microbleed, and enlarged perivascular space were evaluated based on brain MRI. We used multivariate binary logistic regression analysis, multivariate ordinal logistic regression analysis, and mediation analyses to assess the relations of serum tHcy with CSVD and cognitive function.ResultsSerum tHcy levels were higher in patients with cognitive impairment than those with no cognitive impairment. Logistic regression analyses showed elevated serum tHcy was associated with cognitive impairment [odds ratio (OR): 10.475; 95% confidence interval (CI): 4.522 to 24.264; p < 0.001] and a higher CSVD burden score (OR: 17.151; 95% CI: 8.785 to 33.921; p < 0.001) after adjusting potential confounders. Compared with the lowest tHcy quartile, the multivariable-adjusted OR of the highest quartile was 4.851 (95% CI: 3.152 to 7.466; p for the trend < 0.001) for cognitive impairment, 3.862 (95% CI: 2.467 to 6.047; p for the trend < 0.001) for a severe CSVD burden score. Mediation analyses showed significant moderating effects (9.3–23.6%) by different imaging markers of CSVD on the association between higher serum tHcy levels and cognitive impairment.ConclusionElevated serum tHcy is associated with cognitive impairment and the development of CSVD. A proportion of the association between elevated serum tHcy and cognitive impairment may be attributed to the presence of different imaging markers of CSVD, especially the severe CSVD burden score.

Many real-world scenarios can be naturally modeled as heterogeneous graphs, which contain both symmetry and asymmetry information. How to learn useful knowledge from the graph has become one of the hot spots of research in artificial intelligence. Based on Metapath2vec algorithm, an improved Metapath2vec algorithm is presented, which combines Metapath random walk, used to capture semantics and structure information between different nodes of a heterogeneous network, and GloVe model to consider the advantage of global text representation. In order to verify the feasibility and effectiveness of the model, node clustering and link prediction experiments were conducted on the self-generated ideal dataset and the MOOC course data. The analysis of experimental data on these tasks shows that the Metapath–GloVe algorithm learns consistently better embedding of heterogeneous nodes, and the algorithm improves the node embedding performance to better characterize the heterogeneous network structure and learn the characteristics of nodes, which proves the effectiveness and scalability of the proposed method in heterogeneous network mining tasks. It is also shown through extensive experiments that the Metapath–GloVe algorithm is more efficient than the non-negative matrix decomposition algorithm (NMF), and it can obtain better clustering results and more accurate prediction results in the video recommendation task.

Research background and Objectives: Age is an independent risk factor for cardiovascular disease (CVD), but CVD risk factors are preventable, and lack of awareness of its risk factors is a contributing factor to CVDs. Middle-aged people may be more likely to engage in unhealthy lifestyle behaviours which can increase the risk of CVD. Health self-assessment is crucial for early detection and management of health issues and early lifestyle intervention for better personalised health management. This study aims to determine the self-assessment of INTERHEART risk classification among the middle-aged community in Malaysia. Method: Local community members aged 40–60 years and who are currently residing in Malaysia were recruited via non-randomised sampling. Sociodemographic characteristics and dietary pattern related to salt, fibre, fat (deep fried/snacks), poultry/meat intakes, and other cardiovascular risk factors (waist-hip ratio, medical history related to diabetes/hypertension, history/exposure of tobacco use, psychosocial status, and level of physical activity) were assessed; INTERHEART risk scores were then computed and stratified into low, medium and high risks. Results: Approximately 45% (n = 273/602) of middle-aged respondents in Malaysia are at moderate-to-high risk of cardiovascular events, with men being more likely to develop CVD compared to women. The results of the survey indicated that poultry/meat intake (61%), physical inactivity (59%), and second-hand smoke (SHS) exposure (54%) are the most prevalent risk factors among the respondents. One-third of the respondents consumed excessive salty food and deep fried foods/snacks/fast food, and only one-third of them consumed vegetables/fruits at a recommended level. It is worrying that about a quarter of the respondents felt several periodical/permanent stresses and even felt sad/blue/depressed for two weeks or more in a row. Males, labour workers, and those with lower educational levels are more likely to develop CVD events. Conclusions: This study found that 45% of the middle-aged respondents were having moderate-to-high risk for cardiovascular events with multiple risk factors related to unhealthy lifestyle habits and environmental factors. In addition to non-modifiable factors such as gender and age, sociodemographic factors, i.e., educational level and occupation, are equally important factors to determine CVD risk. Overall, the findings of this study emphasize the clinical relevance of assessing multiple factors in the determination of CVD risks for early prevention and management of cardiovascular diseases.

Ultrasound–microwave combined extraction (UMCE), gradient ethanol precipitation, chemical characterization, and antioxidant and hypoglycemic activities of Lycium barbarum leaf polysaccharides (LLP) were systematically studied. The optimal conditions for UMCE of LLP achieved by response surface method (RSM) were as follows: microwave time of 16 min, ultrasonic time of 20 min, particle size of 100 mesh, and ratio of liquid to solid of 55:1. Three novel polysaccharide fractions (LLP30, LLP50, LLP70) with different molecular weights were obtained by gradient ethanol precipitation. Polysaccharide samples exhibited scavenging capacities against ABTS and DPPH radicals and inhibitory activities against α-glucosidase and α-amylase. Among the three fractions, LLP30 possessed relatively high antioxidant and hypoglycemic activities in vitro, which showed a potential for becoming a nutraceutical or a phytopharmaceutical for prevention and treatment of hyperglycemia or diabetes.

With the development of plasma-activated water (PAW) technology, its applications in the fields of food, agriculture, and biomedicine are becoming increasingly widespread. PAW has sterilization, pesticide residue reduction, anti-cancer, and blood clotting functions. Traditional methods for pesticide degradation include home processing, baking and freeze-drying, and UV treatment; however, they generally suffer from poor degradation efficiency and adverse effects on fruit quality. This study found that PAW treatment is a green and efficient environmental technology with the advantages of simple operation, good treatment effect, and no secondary pollution. This paper investigated the efficiency of PAW on the reduction of two acaricides, namely, bifenazate and spirodiclofen, and the effect of PAW treatment on the quality of Cuimi kumquat. The results showed that after PAW treatment, the residual amounts of bifenazate and spirodiclofen were reduced to a minimum of 1.19 mg·kg−1 and 0.23 mg·kg−1, with a reduction of 74.35% and 59.37% respectively compared to the control. Moreover, PAW treatment did not have any negative effects on the storage quality of Cuimi kumquat.

Abstract Background The incidence and risk of tuberculosis (TB) among the elderly population have increased with the ageing population in China. This study aimed to assess the current status and associated factors of TB knowledge, attitudes, and practices among elderly people in Shenzhen City, China, which may provide references for the development of TB prevention and treatment policies targeting elderly people. Methods A multistage random sampling method was used to collect data with a self-designed questionnaire from 1078 elderly people (response rate, 90.66%) living in Bao’an District of Shenzhen between September and October 2019. Univariate and multiple linear regression analyses were used to analyse factors associated with TB knowledge, attitudes, and practices among elderly people. Results Among the respondents, 3.13% had previously been treated for TB, and 3.09% of respondents had family members or friends with a previous TB history. The percentages of elderly people who were aware of TB and had positive attitudes and practices regarding TB were 69.23%, 48.87%, and 42.62%, respectively. Multiple linear stepwise regression analysis showed that elderly people with a junior high school education or higher, a family annual income per capita of less than 100,000 RMB, a better self-perceived health status, and family members or friends with a previous TB history had higher TB knowledge scores (P

Abstract Background The complex interrelationships between professional identity, job satisfaction, burnout, and turnover intention among general practitioners (GPs) are insufficiently understood in China. This study aimed to investigate the interrelationships between professional identity, job satisfaction, burnout, and turnover intention in China, and to examine whether job satisfaction and burnout played mediating roles between professional identity and turnover intention. Methods A cross-sectional survey was conducted between October, 2017 and February, 2018 in China. The participants were selected using a multistage stratified random sampling method. Data were collected with a self-administered questionnaire from 3236 GPs (response rate, 99.8%) working in community health institutions in China. Professional identity was measured by the 13 items scale, and job satisfaction scale with an 11-item designed by Shi et al. was employed. Burnout was measured using a 22-item Maslach Burnout Inventory-Human Services Survey, and turnover intention was measured with a 6 items scale. Descriptive statistics were calculated and groups’ differences were estimated Student’s t-test and analyses of variance. Pearson’s correlation analysis was used to assess the degree of correlation among different dimensions of professional identity, job satisfaction, burnout, and turnover intention. Structural equation modeling analysis was applied to examine the interrelationships among these study variables based on the hypothesized model. Results The proposed model achieved a good model fit. Job satisfaction had a direct negative effect on turnover intention (β = − 0.38, P

Abstract In order to reduce the thermal stress in high chromium cast iron (HCCI) matrix composites reinforced by zirconia toughened alumina (ZTA) ceramic particles, finite element simulation is performed to optimize the geometric configuration of ceramics perform. The previous model simplifies the overall structure of the ceramic particle preform and adds boundary conditions to simulate the particles, which will cause uncontrollable error in the results. In this work, the equivalent grain models are used to describe the actual preform, making the simulation results closer to the actual experimental results. The solidification process of composite material is simulated, and the infiltration between molten iron and ceramic particles is realized. Thermal stress in solidification process and compression stress distribution are obtained. The results show that adding 10-mm round holes on the preform can improve the performance of the composite, which is helpful to prevent the cracks and increases the plasticity of the material.

This study investigates rare earth RE3TaO7 ceramics and shows that these materials may be optimal for thermal barrier coatings. ZrO2-Sm3TaO7 ceramics were prepared through a solid-state reaction. X-ray diffusion and structural refinement revealed a phase structure with an ordered orthorhombic phase for the Ccmm space group. The degree of structural disorder increased with increasing ZrO2 content. Gaussian function fitting of the oxygen 1s X-ray photoelectron spectra showed that the Sm3+ and Ta5+ ions were replaced by Zr4+ ions. At high temperatures, 8 mol% ZrO2-Sm3TaO7 has a high thermal expansion coefficient (10.9 × 10−6 K−1). The thermal conductivities of ZrO2-Sm3TaO7 (1.17 − 1.75 W·m−1 K−1) are lower than those of 7–8 wt.% yttria-stabilized zirconia, while those of 2% ZrO2-Sm3TaO7 are the lowest. The oxygen vacancies maintain the charge in equilibrium and enhance phonon scattering while decreasing the thermal conductivity. These results indicate that Sm3TaO7 can be used as a TBC.