LAPTM4B-35 promotes cancer cell migration via stimulating integrin beta1 recycling and focal adhesion dynamics

Metastasis is the main cause of cancer patients' death despite tremendous efforts invested in developing the related molecular mechanisms. During cancer cell migration, cells undergo dynamic regulation of filopodia, focal adhesion, and endosome trafficking. Cdc42 is imperative for maintaining cell morphology and filopodia, regulating cell movement. Integrin beta1 activates on the endosome, the majority of which distributes itself on the plasma membrane, indicating that endocytic trafficking is essential for this activity. In cancers, high expression of lysosome-associated protein transmembrane 4B (LAPTM4B) is associated with poor prognosis. LAPTM4B-35 has been reported as displaying plasma membrane distribution and being associated with cancer cell migration. However, the detailed mechanism of its isoform-specific distribution and whether it relates to cell migration remain unknown. Here, we first report and quantify the filopodia localization of LAPTM4B-35: mechanically, that specific interaction with Cdc42 promoted its localization to the filopodia. Furthermore, our data show that LAPTM4B-35 stabilized filopodia and regulated integrin beta1 recycling via interaction and cotrafficking on the endosome. In our zebrafish xenograft model, LAPTM4B-35 stimulated the formation and dynamics of focal adhesion, further promoting cancer cell dissemination, whereas in skin cancer patients, LAPTM4B level correlated with poor prognosis. In short, this study establishes an insight into the mechanism of LAPTM4B-35 filopodia distribution, as well as into its biological effects and its clinical significance, providing a novel target for cancer therapeutics development.Peer reviewe

Single botanical drugs in the Ayurvedic Pharmacopoeia of India—A quantitative ethnobotanical analysis

Developing evidence-based uses of herbal medicines and natural product-based drug discovery are two core aims of ethnopharmacology. This requires an understanding of the medicinal plants and the traditional medical knowledge associated with them which is a basis for cross-cultural comparison. The botanical drugs of traditional medical systems are still not understood well, even for well-known and widely respected traditions like Ayurveda. In this study, a quantitative ethnobotanical analysis was performed on the single botanical drugs included in the Ayurvedic Pharmacopoeia of India (API), presenting an overview on the medicinal plants of Ayurveda from perspectives of plant systematics and medical ethnobotany. Part-I of API includes 621 single botanical drugs, which are sourced from 393 species (323 genera in 115 families). Of these, 96 species yield two or more drugs, together accounting for 238 drugs. Taking the traditional concepts, biomedical uses and the pragmatic disease classification into account, therapeutic uses of these botanical drugs are sorted into 20 categories, which meet primary health demands. The therapeutic uses of the drugs sourced from the same species may differ considerably, but 30 of the 238 drugs are used in highly similar way. The comparative phylogenetic analysis identifies 172 species with high potential for specific therapeutic uses. This medical ethnobotanical assessment for the first time provides a comprehensive understanding on the single botanical drugs in API from the perspective of medical botany using an “etic” (scientist-oriented) approach. This study also highlights the importance of quantitative ethnobotanic methods in understanding traditional medical knowledge

A modified modulation scheme for three-level diode-clamped matrix converter under unbalanced input conditions

The three-level diode-clamped matrix converter topology has outstanding performance under ideal operating conditions. However, input disturbance can influence the waveforms at the output side of the converter due to the direct coupling between the input and output. This paper proposes a modified modulation scheme for three-level diode-clamped matrix converter during operation with unbalanced input voltages and when different transformer turns ratios are used for an isolation transformer at the input. With this modulation technique, sinusoidal and balanced output voltages are guaranteed and the input current harmonics are minimized. Experimental results are presented to demonstrate the feasibility and effectiveness of the proposed modulation scheme

Factors influencing inappropriate use of antibiotics in outpatient and community settings in China: a mixed-methods systematic review.

BACKGROUND: For decades, antibiotics have been excessively consumed around the world, contributing to increased antimicrobial resistance (AMR) and negatively impacting health outcomes and expenditures. Antibiotic use in China accounts for half of worldwide antibiotic consumption, which mainly takes place in outpatient and community settings, and often unnecessarily for self-limiting community-acquired infections. This study aimed to identify and assess factors of inappropriate use of antibiotics in the Chinese context to inform the development of interventions to mitigate inappropriate consumption in the absence of clinical indications. METHODS: We conducted a mixed-methods systematic review and included empirical studies with original data conducted in mainland China, Hong Kong and Taiwan that investigated factors of antibiotic use in the community including outpatient care among patients, caregivers and prescribers. We searched MEDLINE, EMBASE, the Cochrane Library, PsycINFO, Google Scholar and one Chinese database CNKI (China Knowledge Resource Integrated Database), using a combination of the key terms 'antibiotic', 'antimicrobial', 'use', 'consumption', 'behaviour', 'prescribe' and related syntax for all peer-reviewed publications published before June 2020. Health Belief Model was employed for data synthesis. FINDINGS: Fifty-four studies were included in the full-text review: 44 quantitative, 5 qualitative and 5 mixed-methods studies. Despite a high AMR awareness, public perception/misconception of antibiotic efficacy and easy access to antibiotics for self-limiting conditions drive inappropriate demand and use in the community including primary care setting. Providers' prescribing behaviours are influenced by financial incentives, lack of diagnostic capacity and concerns over complications. CONCLUSIONS: Inappropriate outpatient and community antibiotic use is influenced by non-biomedical factors at the individual, community, health system and societal levels in mainland China, contributing to a high antibiotic use rate. This study calls for context-tailored One Health interventions, restrictive antibiotic drug policy and multifaceted antibiotic stewardship programmes that simultaneously address drivers of inappropriate use from both the supply-side and demand-side within and beyond clinical settings. PROSPERO REGISTRATION NUMBER: CRD42019139591

Study on pathological and clinical characteristics of chronic HBV infected patients with HBsAg positive, HBV DNA negative, HBeAg negative

AimsStudy of clinical characteristics of hepatitis B virus deoxyribonucleic acid (HBV DNA)-negative, hepatitis B surface antigen (HBsAg)-positive, hepatitis B e antigen (HBeAg)-negative patients based on liver histopathology.MethodsWe retrospectively enrolled patients with chronic HBV infection diagnosis at Beijing Ditan Hospital from May 2008 to November 2020. To study the differences between patients with significant hepatic histopathology and those without significant hepatic histopathology. And to study the independent factors of significant hepatic histopathology.Results85 HBV DNA-negative and HBeAg-negative patients were 37.90 ± 10.30 years old, 23.50% of patients with grade of inflammation (G) >1, 35.30% of patients with liver fibrosis stage (S) >1, 44.70% patients were diagnosed with significant hepatic histopathology. Compared to the no significant hepatic histopathology group, another group had older age (41.70 ± 10.70 vs 34.80 ± 8.87 years, t=-3.28, P=0.002), higher total bilirubin (TBIL) [14.9(10.3, 22.4) vs 11(8.9, 14.4) μmol/L, z=-2.26, P=0.024], lower cholinesterase (CHE) (t=-2.86, P=0.005, 7388.00 ± 2156.00 vs 8988.00 ± 2823.00 U/L) and lower platelet (PLT) (t=2.75, P=0.007, 157.00 ± 61.40 vs 194.00 ± 61.00 10^9/L). Abnormal ALT patients are more likely to have significant hepatic histopathology (z=5.44, P=0.020, 66.70% vs 337.50%). G had significant correlation with CHE (P=0.008, r=-0.23), alanine aminotransferase (ALT) (P=0.041, r=0.18), aspartate aminotransferase (AST) (P=0.001, r=0.29). S had significant correlation with TBIL (P = 0.008, r = 0.23), age (P < 0.001, r = 0.32), international normalized ratio (INR) (P = 0.04, r = 0.23), CHE (P < 0.001, r = -0.30), PLT (P < 0.001, r = -0.40) and prothrombin time activity (PTA) (P = 0.046, r = -0.22). Multivariate logistic analysis indicated only age (95%CI=1.014~1.130, OR=1.069, P=0.013) was an impact factor for significant hepatic histopathology. The cutoff point of age was 34.30 years.ConclusionsA large proportion of chronic HBV infection patients with HBeAg-negative and HBV DNA-negative still have chronic hepatitis. Age is an independent factor for significant hepatic histopatholog

Quality control of goji (fruits of Lycium barbarum L. and L. chinense Mill.): A value chain analysis perspective

Ethnopharmacological relevance Goji (fruits of Lycium barbarum L. and L. chinense Mill., Solanaceae) have been used as a traditional food and medicine for hundreds of years in Asian countries and are now consumed globally. Quality of herbal medicines is critical for safe use and has been shown to be affected by value chains. Aim of the study Using a value chain (VC) framework, we aim at understanding the influence of different VC types on goji quality and revenue of stakeholders. Materials and methods Participant observation and semi-structured interviews were conducted during five months of fieldwork in the main production areas in China with a total of 65 stakeholders. Quality of goji, behaviour and financial performance of stakeholders was documented and analysed for different VCs. Results Ten different types of VCs were identified. VCs with vertical integration and horizontal collaboration were found to have a more coherent quality control and better goji quality as well as improved stakeholders’ financial performance. Vertical integration at different levels was found for independent farmer-based VCs, horizontal collaboration was found in the cooperative-based VCs. Full vertically integrated VCs were found in large-scale production. Conclusions Goji quality and stakeholders’ revenues are linked with different types of VCs which mirror stakeholders’ behaviour driven by target markets. Considering their positive influence on quality and revenues, well-developed vertically integrated value chains are likely to become more important in the near future

Non-biomedical factors affecting antibiotic use in the community: a mixed-methods systematic review and meta-analysis

Objectives: In the past two decades, human antibiotic consumption has increased globally, contributing to the emergence and spread of antimicrobial resistance and needing urgent effective actions. Our objectives were to systematically identify and collate studies exploring non-biomedical factors influencing healthcare consumers' antibiotic use globally, in order to inform future interventions to improve practices in antibiotic use. Methods: Data sources were PubMed, EMBASE, PsycINFO, and Cochrane. Study eligibility criteria were original and empirical studies that identified factors for healthcare consumers' antibiotic use. Participants were healthcare consumers. Assessment of risk of bias used adapted BMJ survey appraisal tools, the Critical Appraisal Skills Programme checklist, and the Mixed Methods Appraisal Tool for quality assessment. Methods of data synthesis employed the Social Ecological Framework and Health Belief Model for data synthesis. We did random-effects meta-analyses to pool the odds ratios of risk factors for antibiotic use. Results: We included 71 articles for systematic review and analysis; 54 were quantitative, nine were qualitative, and eight were mixed-methods studies. Prevalent non-prescription antibiotic use and irresponsible prescriptions were reported globally, especially in low-to-middle-income countries. Barriers to healthcare-wait time, transportation, stigmatization-influenced people's practices in antibiotic use. Further, lack of oversight and regulation in the drug manufacturing and a weak supply chain have led to the use of substandard or falsified antibiotics. Knowledge had mixed effects on antibiotic use behaviours. Meta-analyses identified pro-attitudes towards self-medication with antibiotics, relatives having medical backgrounds, older age, living in rural areas, and storing antibiotics at home to be risk factors for self-medication with antibiotics. Conclusions: Non-prescription antibiotic use and irresponsible prescriptions in the community are prevalent in all WHO regions and are driven largely by a mixed collection of non-biomedical factors specific to the respective setting. Future antimicrobial resistance strategies should incorporate an implementation science approach for community-based complex interventions that address drivers of the target behaviours tailored to local contexts.</p

Enantiomer separations on a vancomycin stationary phase and retention mechanism of pressurized capillary electrochromatography

Several chiral drugs, promethazine, carteolol, celiprolol, and albuterol, were resolved with vancomycin as the chiral stationary phase by pressurized capillary electrochromatography (pressurized CEC) and capillary HPLC. The effects of pressure and electrical field strength on efficiency, resolution, and capacity factor in pressurized CEC were investigated. A mathematical model describing the relationship of capacity factor in pressurized CEC with voltage, pressurized flow velocity, electroosmotic mobility, and electrophoretic mobility was established, which was in good agreement with the experimental data