Phenolic constituents from the branches of Viburnum chinshanense as potential α-amylase and α-glucosidase inhibitory agents.

This paper reports the isolation of two undescribed phenolic glycosides (1 and 2), together with seven known compounds (3-9) from the branches of Viburnum chinshanense. The structures of undescribed compounds were elucidated by comprehensive spectroscopic methods (1D NMR, 2D NMR, and HRESIMS). The sugar units of compounds 1 and 2 were identified by acid hydrolysis and HPLC analysis of the chiral derivatives of the monosaccharides. Furthermore, the α­amylase and α-glucosidase inhibitory activities of all isolates were evaluated and compounds 1, 5, and 8 displayed potential α­amylase and α-glucosidase inhibitory activities. The molecular docking analyses of compounds 1 and 8 with the potent inhibition towards the target enzymes were also performed.

Inflammatory risk of albumin combined with C-reactive protein predicts long-term cardiovascular risk in patients with diabetes.

AIMS: The purpose of this study was to evaluate the predictive value of inflammatory risk as defined by the Glasgow Prognostic Score (GPS) for cardiovascular death in patients with diabetes. METHODS: This study included 4956 patients (≥18 years old) with diabetes in the National Health and Nutrition Survey from 1999 to 2010. The mortality rate was determined by the correlation with the national death index on December 31, 2019. The GPS was composed of the serum C-reactive protein and the albumin. The primary outcome was cardiovascular death and the secondary outcome was all-cause death. The Cox proportional risk model adjusted for demographic factors and traditional cardiovascular risk factors was used to analyze the cumulative risk of outcomes. RESULTS: Among 4956 diabetes patients with a median follow-up of 10.9 years, 601 cardiovascular deaths and 2187 all-cause deaths were recorded. After adequate model adjustment, compared with the low GPS group, the high GPS group (HR, 1.257 (1.007-1.570), P = 0.043) had a higher cardiovascular mortality. Compared with the low GPS group, the all-cause mortality of the high GPS group (HR, 1.394 (1.245-1.560), P < 0.001) was higher. The results of subgroup analyses were similar with that of the overall cohort. CONCLUSIONS: The inflammatory risk as defined by the GPS was closely related to the increased risk of cardiovascular and all-cause death in patients with diabetes. It may be a convenient and efficient clinical practical risk assessment tool for patients with diabetes.

Phenolic Glycosides from Viburnum chinshanense Leaves and their α-Amylase and α-Glucosidase Inhibitory Activity.

The phytochemical investigation of Viburnum chinshanense leaves led to the isolation and identification of four new phenolic glycosides, viburninsides A-D (1-4), and eight known analogues (5-12). The structures of the four undescribed compounds were determined by spectroscopic techniques, including 1D NMR, 2D NMR, and HRESIMS, and their containing sugar units were confirmed by acid hydrolysis and HPLC analysis of the monosaccharide's chiral derivatives. Additionally, the α-amylase and α-glucosidase inhibitory activities of the isolated compounds were assessed. Compounds 1, 2, 4, 9, and 10 exhibited potential inhibitory activities against α-amylase and α-glucosidase with IC50 values ranging from 35.07 µM to 47.42 µM and 18.27 µM to 43.65 µM, respectively. Molecular docking analysis of compound 4 with the strongest inhibition against the target enzymes was also conducted.

Quality appraisal and descriptive analysis of clinical practice guidelines for self-managed non-pharmacological interventions of cardiovascular diseases: a systematic review.

BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of death around the world. Most CVDs-related death can be prevented by the optimal management of risk factors such as unhealthy diet and physical inactivity. Clinical practice guidelines (CPGs) for CVDs, provide some evidence-based recommendations which help healthcare professionals to achieve the best care for patients with CVDs. This systematic review aims to appraise the methodological quality of CPGs systematically and summarize the recommendations of self-managed non-pharmacological interventions for the prevention and management of CVDs provided by the selected guidelines. METHODS: A comprehensive electronic literature search was conducted via six databases (PubMed, Medline, The Cochrane Library, Embase, CINAHL, and Web of Science), seven professional heart association websites, and nine guideline repositories. The Appraisal of Guidelines, Research and Evaluation II (AGREE II) instrument was adopted to critically appraise the methodological quality of the selected guidelines. Content analysis was used to summarise recommended self-managed non-pharmacological interventions for CVDs. RESULTS: Twenty-three CPGs regarding different CVDs were included, in which four guidelines of CVDs, three for coronary heart diseases, seven for heart failure, two for atrial fibrillation, three for stroke, three for peripheral arterial disease, and one for hypertrophic cardiomyopathy. Twenty CPGs were appraised as high quality, and three CPGs as moderate quality. All twenty-three CPGs were recommended for use with or without modification. The domain of "Editorial Independence" had the highest standardized percentage (93.47%), whereas the domain of "Applicability" had the lowest mean domain score of 75.41%. The content analysis findings summarised some common self-managed non-pharmacological interventions, which include healthy diet, physical activity, smoking cessation, alcohol control, and weight management. Healthy diet and physical acidity are the most common and agreed on self-managed interventions for patients with CVDs. There are some inconsistencies identified in the details of recommended interventions, the intervention itself, the grade of recommendation, and the supported level of evidence. CONCLUSION: The majority of the summarized non-pharmacological interventions were strongly recommended with moderate to high-quality levels of evidence. Healthcare professionals and researchers can adopt the results of this review to design self-managed non-pharmacological interventions for patients with CVDs.

Lignan and phenolic glycosides from Viburnum betulifolium fruits and their α­amylase and α-glucosidase inhibitory activities.

The phytochemical investigation on the methanol extract of Viburnum betulifolium fruits resulted in the isolation and identification of two new lignan constituents (1 and 2) and seven known phenolic glycosides (3-9). The structures of new isolates, including their absolute configurations were elucidated by extensive spectroscopic analyses (1H and 13C NMR, HSQC, HMBC, HRESIMS, and ECD) and chemical methods. In the in vitro enzyme assays, compounds 1, 2, 6, and 8 showed potential α­amylase and α-glucosidase inhibitory activities. Among them, compound 1 exhibited stronger inhibitory effects towards α-amylase and α-glucosidase with the IC50 values of 12.68 and 15.17 µM, respectively, than those of the positive control acarbose (IC50, 29.19 and 18.15 µM, respectively). In addition, the molecular docking analyses of compound 1 with strongest inhibition against the target enzymes were also performed.

Potentiation and Mechanism of Berberine as an Antibiotic Adjuvant Against Multidrug-Resistant Bacteria.

The growing global apprehension towards multi-drug resistant (MDR) bacteria necessitates the development of innovative strategies to combat these infections. Berberine (BER), an isoquinoline quaternary alkaloid derived from various medicinal plants, has surfaced as a promising antibiotic adjuvant due to its ability to enhance the effectiveness of conventional antibiotics against drug-resistant bacterial strains. Here, we overview the augmenting properties and mechanisms of BER as an adjunctive antibiotic against MDR bacteria. BER has been observed to exhibit synergistic effects when co-administered with a range of antibiotics, including ß-lactams, quinolones, aminoglycosides, tetracyclines, macrolides, lincosamides and fusidic acid. The adjunctive properties of BER led to an increase in antimicrobial effectiveness for these antibiotics against the corresponding bacteria, a decrease in minimal inhibitory concentrations, and even the reversal from resistance to susceptibility sometimes. The potential mechanisms responsible for these effects included the inhibition of antibiotic efflux, the disruption of biofilm formation, the modulation of host immune responses, and the restoration of gut microbiota homeostasis. In brief, BER demonstrated significant potential as an antibiotic adjuvant against MDR bacteria and is a promising candidate for combination therapy. Further research is necessary to fully elucidate its mechanism of action and address the challenges associated with its clinical application.

Lignan constituents with α-amylase and α-glucosidase inhibitory activities from the fruits of Viburnum urceolatum.

Eleven previously undescribed lignan constituents, including five 8-O-4' type neolignans, viburnurcosides A-E (1-5), three benzofuran type neolignans, viburnurcosides F-H (6-8), and three tetrahydrofuran type lignans, viburnurcosides I-K (9-11), were isolated from the fruits of Viburnum urceolatum. The structures of all isolates were elucidated by an extensive analysis of the NMR and HRESIMS data. The absolute configurations of these compounds were determined by quantum-chemical electronic circular dichroism calculation and comparison. The sugar units of viburnurcosides A-K were identified by acid hydrolysis and HPLC analysis of the chiral derivatives of monosaccharides. The in vitro enzyme inhibition assay exhibited that viburnurcoside J (10) had the most potent inhibitory activity against α-amylase and α-glucosidase with the IC50 values of 19.75 and 9.14 µM, respectively, which were stronger than those of the positive control acarbose (37.31 and 26.75 µM, respectively). The potential binding modes of viburnurcoside J (10) with α-amylase and α-glucosidase were also analyzed by molecular modeling.

Iridoid constituents from the branches of Viburnum chinshanense and their inhibitory effects on α-amylase and α-glucosidase.

Ten previously undescribed iridoid constituents, viburnshosins A-E (1-5) and viburnshosides A-E (6-10), together with one known analogue (11), were isolated from the branches of Viburnum chinshanense. Their structures were unambiguously elucidated by a comprehensive analysis of 1D and 2D NMR data, together with HRESIMS spectroscopic data. The absolute configurations of compounds 1-10 were assigned by means of the calculated ECD spectra. Interestingly, compounds 2 and 3 are the first iridoids with an unusual C-3-C-7 oxo bridge. Compounds 4, 5, and 10 displayed remarkable inhibitory effects against α-amylase (IC50: 38.42, 37.65, and 21.64 µM, respectively) and α-glucosidase (IC50: 12.97, 19.34, and 25.71 µM, respectively), comparable to those of the positive control acarbose (IC50: 39.75 and 23.66 µM, respectively). The interaction modes of compounds 4 and 10 with two enzymes were analyzed by molecular modeling.

SMYD3 induces sorafenib resistance by activating SMAD2/3-mediated epithelial-mesenchymal transition in hepatocellular carcinoma.

Drug resistance prominently hampers the effects of systemic therapy of sorafenib to hepatocellular carcinoma (HCC). Epigenetics have critical regulatory roles in drug resistance. However, the contributions of histone methylatransferase SET and MYND domain containing 3 (SMYD3) to sorafenib resistance in HCC remain largely unknown. Here, using our established sorafenib-resistant HCC cell and xenograft models, we found SMYD3 was markedly elevated in sorafenib-resistant tumors and cells. Functionally, loss- and gain-of-function studies showed that SMYD3 promoted the migration, invasion, metastasis and stemness of sorafenib-resistant HCC cells. Mechanistically, SMYD3 is required for SMAD2/3-mediated epithelial-mesenchymal transition (EMT) in sorafenib-resistant HCC cells by interacting with SMAD2/3 and epigenetically promoting the expression of SOX4, ZEB1, SNAIL1 and MMP9 genes. In summary, our data demonstrate that targeting SMYD3 is an effective approach to overcome sorafenib resistance in HCC.

Five New Phenolic Glycosides from Viburnum luzonicum.

Viburnum luzonicum is widely distributed in China. Its branch extracts showed potential α-amylase and α-glucosidase inhibitory activities. In order to discover new bioactive constituents, five undescribed phenolic glycosides, viburozosides A-E (1-5), were obtained by bioassay-guided isolation coupled with HPLC-QTOF-MS/MS analysis. Their structures were elucidated by spectroscopic analyses, including 1D NMR, 2D NMR, ECD, and ORD. All compounds were tested for their α-amylase and α-glucosidase inhibitory potency. Compound 1 showed significantly competitive inhibition against α-amylase (IC50 =17.5 µM) and α-glucosidase (IC50 =13.6 µM).

LC-MS guided isolation of phenolic glycosides from Viburnum luzonicum Rolfe leaves and their α­amylase and α-glucosidase inhibitory activities.

Viburnum luzonicum Rolfe is widely used in China as folk medicine. The bioactivity evaluation indicated that the n-BuOH fraction of V. luzonicum leaves (VLLB) could significantly inhibit α­amylase and α-glucosidase. In order to clarify its active constituents, the phytochemical analysis on VLLB was first performed using HPLC-QTOF-MS/MS, and three new phenolic compounds, viburosides A-C (1-3), along with seven known analogues (4-10) were isolated through preparative HPLC. The undescribed compounds were determined by extensive spectroscopic analyses (1H and 13C NMR, HSQC, HMBC, HRESIMS, and ORD) and enzymatic hydrolysis. In the in vitro enzyme assays, compounds 1-8 showed potent α­amylase and α-glucosidase inhibitory activities. The enzymatic kinetics and molecular docking of the strongest inhibitors 2 and 3 against the corresponding target enzyme were also performed.

Influencing factors of medical device-related pressure ulcers in medical personnel during the COVID-19 pandemic: A systematic review and meta-analysis.

OBJECTIVE: To determine the influencing factors of medical device related pressure injury (MDRPU) in medical staff by meta-analysis. METHODS: A comprehensive literature search was conducted by PubMed, Embase, Cochrane Library, Web of Science, CNKI, VIP, CBM, and WanFang Data (from inception to July 27, 2022). Two researchers independently performed literature screening, quality evaluation and data extraction, and meta-analysis was conducted with RevMan 5.4 and Stata12.0 software. RESULTS: Total of 11215 medical staff were included in 9 articles. Meta analysis showed that gender, occupation, sweating, wearing time, single working time, department of COVID-19, preventive measures, and level 3 PPE were the risk factors for MDRPU in medical staff (P < 0.05). CONCLUSION: The outbreak of COVID-19 led to the occurrence of MDRPU among medical staff, and the influencing factors should be focused on. The medical administrator can further improve and standardize the preventive measures of MDRPU according to the influencing factors. Medical staff should accurately identify high-risk factors in the clinical work process, implement intervention measures, and reduce the incidence of MDRPU.

Effects of exercise interventions on cancer-related fatigue in breast cancer patients: an overview of systematic reviews.

OBJECTIVE: This overview of systematic reviews aims to critically appraise and consolidate evidence from current systematic reviews (SRs)/meta-analyses on the effects of exercise interventions on cancer-related fatigue (CRF) in breast cancer patients. METHODS: SRs/meta-analyses that explored the effects of exercise interventions on CRF in breast cancer patients compared with the routine methods of treatment and care were retrieved from nine databases. The methodological quality of the included SRs was appraised using A MeaSurement Tool to Assess systematic Reviews II (AMSTAR II). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to calculate the grading of outcomes in the included SRs. The exercise type, frequency, duration, and inclusion/absence of supervision were further evaluated with subgroup analyses. The Stata 16.0 software was utilized for data analysis. RESULTS: Twenty-nine reviews were included. The overall methodological quality and level of evidence of the included reviews were unsatisfactory, with only three reviews rated as high methodological quality and no review identified as high-quality evidence. Moderate certainty evidence indicated that exercise could improve fatigue in breast cancer patients (SMD = - 0.40 [95%CI - 0.58, - 0.22]; P = 0.0001). Subgroup analysis based on the types of exercise showed that yoga (SMD = - 0.30 [95%CI - 0.56, - 0.05]; I2 = 28.7%) and aerobic exercise (SMD = - 0.29 [95%CI - 0.56, - 0.02]; I2 = 16%) had a significantly better effect on CRF in breast cancer patients; exercising for over 6 months (SMD = - 0.88 [95%CI - 1.59, - 0.17]; I2 = 42.7%; P = 0.0001), three times per week (SMD = - 0.77 [95%CI - 1.04, - 0.05]; I2 = 0%; P = 0.0001), and for 30 to 60 min per session (SMD = - 0.81 [95%CI - 1.15, - 0.47]; I2 = 42.3%; P = 0.0001) can contribute to a moderate improvement of CRF. Supervised exercise (SMD = - 0.48 [95%CI - 0.77, - 0.18]; I2 = 87%; P = 0.001) was shown to relieve CRF. CONCLUSION: Exercise played a favorable role in alleviating CRF in breast cancer. Yoga was recommended as a promising exercise modality for CRF management in the majority of the included studies. Exercising for at least three times per week with 30 to 60 min per session could be recommended as a suitable dosage for achieving improvement in CRF. Supervised exercise was found to be more effective in alleviating CRF than unsupervised exercise. More rigorously designed clinical studies are needed to specify the exact exercise type, duration, frequency, and intensity to have an optimal effect on CRF in breast cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: CRD42020219866.

Lightweight multi-scale network for small object detection.

Small object detection is widely used in the real world. Detecting small objects in complex scenes is extremely difficult as they appear with low resolution. At present, many studies have made significant progress in improving the detection accuracy of small objects. However, some of them cannot balance the detection speed and accuracy well. To solve the above problems, a lightweight multi-scale network (LMSN) was proposed to exploit the multi-scale information in this article. Firstly, it explicitly modeled semantic information interactions at every scale via a multi-scale feature fusion unit. Secondly, the feature extraction capability of the network was intensified by a lightweight receptive field enhancement module. Finally, an efficient channel attention module was employed to enhance the feature representation capability. To validate our proposed network, we implemented extensive experiments on two benchmark datasets. The mAP of LMSN achieved 75.76% and 89.32% on PASCAL VOC and RSOD datasets, respectively, which is 5.79% and 11.14% higher than MobileNetv2-SSD. Notably, its inference speed was up to 61 FPS and 64 FPS, respectively. The experimental results confirm the validity of LMSN for small object detection.

Strip thickness prediction method based on improved border collie optimizing LSTM.

Background: The thickness accuracy of strip is an important indicator to measure the quality of strip, and the control of the thickness accuracy of strip is the key for the high-quality strip products in the rolling industry. Methods: A thickness prediction method of strip based on Long Short-Term Memory (LSTM) optimized by improved border collie optimization (IBCO) algorithm is proposed. First, chaotic mapping and dynamic weighting strategy are introduced into IBCO to overcome the shortcomings of uneven initial population distribution and inaccurate optimization states of some individuals in Border Collie Optimization (BCO). Second, Long Short-Term Memory (LSTM) which can effectively deal with time series data and alleviate long-term dependencies is adopted. What's more, IBCO is utilized to optimize parameters to mitigate the influence of hyperparameters such as the number of hidden neurons and learning rate on the prediction accuracy of LSTM, so IBCO-LSTM is established. Results: The experiments are carried out on the measured strip data, which proves the excellent prediction performance of IBCO-LSTM. The experiments are carried out on the actual strip data, which prove that IBCO-LSTM has excellent capability of prediction.

Malnutrition is Associated with an Increased Risk of Death in Hospitalized Patients with Active Pulmonary Tuberculosis: A Propensity Score Matched Retrospective Cohort Study.

Background: This study aimed to investigate whether nutrition levels in patients with active pulmonary tuberculosis (TB) affect their risk of all-cause mortality during hospitalization and to further evaluate the predictive ability of Geriatric Nutritional Risk Index (GNRI) and Body Mass Index (BMI) for risk of all-cause mortality. Methods: Patients from January 1, 2020 to December 31, 2021 were retrieved, and a total of 1847 were included. The primary outcome was all-cause mortality. Propensity score matching (PSM) was performed for risk adjustment, and receiver operating characteristic (ROC) curve analysis was performed to assess the predictive ability of GNRI and BMI for all-cause mortality. Results: Malnourished TB patients were older, had more congestive heart failure, and had more chronic obstructive pulmonary disease or asthma. Under the nutrition level grouping defined by GNRI, the all-cause mortality in the malnourished group did not appear to reach a statistical difference compared with the nonmalnourished group (P = 0.078). When grouped by level of nutrition as defined by BMI, the all-cause mortality was higher in the malnourished group (P = 0.009), and multivariate logistic regression analysis revealed that malnutrition was an independent risk factor for all-cause mortality. After propensity score matching, the results showed that the all-cause mortality was higher in the malnutrition group, regardless of BMI or GNRI defined nutrition level grouping, compared with the control group (both P < 0.001). The ROC curve analysis revealed that the area under the curve (AUC) was 0.811 ([95% confidence interval (CI) 0.701-0.922], P < 0.001) for GNRI and 0.728 ([95% CI 0.588-0.869], P = 0.001) for BMI. Conclusion: In the clinical treatment of patients with active TB, more attention should be paid to the management of nutritional risk. GNRI may be a highly effective and easy method for predicting short-term outcomes in patients with active pulmonary TB.

Risk Assessment of Major Adverse Cardiovascular and Cerebrovascular Events and Bleeding for Acute Myocardial Infarction With or Without Active Tuberculosis.

PURPOSE: The underlying ischemic and bleeding risks of acute myocardial infarction (AMI) with active tuberculosis (TB) are unknown. The goal of this study was to explore the ischemic and bleeding risks, as well as treatment strategies during hospitalization, in patients with AMI with or without active TB. METHODS: Patients were recruited from a tuberculosis hospital from 2014 to 2021. The primary outcomes were major cardiovascular and cerebrovascular events (MACE) and Bleeding Academic Research Consortium (BARC)-defined type 3 or 5 bleeding. Multivariate logistic regression and propensity score matching were performed for risk adjustment. Subgroups were defined according to AMI with active pulmonary TB and AMI with active TB undergoing percutaneous coronary intervention (PCI). FINDINGS: A total of 242 patients were enrolled. Compared with AMI without active TB, AMI with active TB had a higher risk of MACE and BARC type 3 or 5 bleeding (P < 0.001 and P = 0.002, respectively). Multivariate logistic regression analysis showed that, compared with AMI without active TB, the odds ratio (OR) was 6.513 (95% CI, 2.195-19.331) for MACE in patients with AMI with active TB, and the OR was 16.074 (95% CI 3.337-77.436) for BARC type 3 or 5 bleeding in patients with AMI with active TB. After propensity score matching, AMI with active TB tended to increase the risk of MACE, although not statistically significantly (P = 0.189), and increased BARC type 3 or 5 bleeding (P < 0.001), compared with AMI without active TB. Results of subgroup analyses showed that active TB had outcomes consistent with those of the total cohort. AMI patients with active pulmonary TB who underwent PCI had a lower risk of MACE without an increase in the risk of bleeding compared with those not undergoing PCI. IMPLICATIONS: Patients with AMI with active TB have a higher risk of MACE (or severe MACE) and bleeding than patients with AMI without active TB. However, AMI patients with active TB are still advised to undergo PCI for a high net clinical benefit.

Impacts of demographic and environmental stochasticity on population dynamics with cooperative effects.

Different types of stochasticity play essential roles in shaping complex population dynamics. This paper presents a novel approach to model demographic and environmental stochasticity in a single-species model with cooperative components that are measured by component Allee effects. Our work provides rigorous mathematical proof on stochastic persistence and extinction, ergodicity (i.e., the existence of a unique stationary distribution) and the existence of a nontrivial periodic solution to study the impacts of demographic and environmental stochasticity on population dynamics. The theoretical and numerical results suggest that stochasticity may affect the population system in a variety of ways, specifically: (i) In the weak Allee effects case (e.g., strong cooperative efforts), the demographic stochasticity from the attack rate contributes to the expansion of the population size, while the demographic stochasticity from the handling rate and the environmental stochasticity have the opposite role, and may even lead to population extinction; (ii) In the strong Allee effects case (cooperative efforts not strong enough), both demographic and environmental stochasticity play a similar role in the survival of population, and are related to the initial population level: if the initial population level is large enough, demographic stochasticity and environmental stochasticity may be detrimental to the survival of population, otherwise if the initial population level is small enough, demographic stochasticity and environmental stochasticity may bring survival opportunities for the population that deterministically would extinct indefinitely; (iii) In the extinction case, demographic and environmental stochasticity cannot change the trend of population extinction, but they can delay or promote population extinction.

Potential inhibitors for blocking the interaction of the coronavirus SARS-CoV-2 spike protein and its host cell receptor ACE2.

BACKGROUND: The outbreak of SARS-CoV-2 continues to pose a serious threat to human health and social. The ongoing pandemic of COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made a serious threat to public health and economic stability worldwide. Given the urgency of the situation, researchers are attempting to repurpose existing drugs for treating COVID-19. METHODS: We first established an anti-coronavirus drug screening platform based on the Homogeneous Time Resolved Fluorescence (HTRF) technology and the interaction between the coronavirus spike protein and its host receptor ACE2. Two compound libraries of 2,864 molecules were screened with this platform. Selected candidate compounds were validated by SARS-CoV-2_S pseudotyped lentivirus and ACE2-overexpressing cell system. Molecular docking was used to analyze the interaction between S protein and compounds. RESULTS: We identified three potential anti-coronavirus compounds: tannic acid (TA), TS-1276 (anthraquinone), and TS-984 (9-Methoxycanthin-6-one). Our in vitro validation experiments indicated that TS-984 strongly inhibits the interaction of the coronavirus S protein and the human cell ACE2 receptor. Additionally, tannic acid showed moderate inhibitory effect on the interaction of S protein and ACE2. CONCLUSION: This platform is a rapid, sensitive, specific, and high throughput system, and available for screening large compound libraries. TS-984 is a potent blocker of the interaction between the S-protein and ACE2, which might have the potential to be developed into an effective anti-coronavirus drug.

Self-Managed Non-Pharmacological Interventions for Breast Cancer Survivors: Systematic Quality Appraisal and Content Analysis of Clinical Practice Guidelines.

Background: A growing number of clinical practice guidelines (CPGs) regarding non-pharmacological interventions for breast cancer survivors are available. However, given the limitations in guideline development methodologies and inconsistent recommendations, it remains uncertain how best to design and implement non-pharmacological strategies to tailor interventions for breast cancer survivors with varied health conditions, healthcare needs, and preferences. Aim: To critically appraise and summarise available non-pharmacological interventions for symptom management and health promotion that can be self-managed by breast cancer survivors based on the recommendations of the CPGs. Methods: CPGs, which were published between January 2016 and September 2021 and described non-pharmacological interventions for breast cancer survivors, were systematically searched in six electronic databases, nine relevant guideline databases, and five cancer care society websites. The quality of the included CPGs was assessed by four evaluators using The Appraisal of Guidelines for Research and Evaluation, second edition tool. Content analysis was conducted to synthesise the characteristics of the non-pharmacological interventions recommended by the included CPGs, such as the intervention's form, duration and frequency, level of evidence, grade of recommendation, and source of evidence. Results: A total of 14 CPGs were included. Among which, only five were appraised as high quality. The "range and purpose" domain had the highest standardized percentage (84.61%), while the domain of "applicability" had the lowest (51.04%). Five CPGs were rated "recommended", seven were "recommended with modifications", and the other two were rated "not recommended". The content analysis findings summarised some commonly recommended self-managed non-pharmacological interventions in the 14 guidelines, including physical activity/exercise, meditation, hypnosis, yoga, music therapy, stress management, relaxation, massage and acupressure. Physical activity/exercise was the most frequently recommended approach to managing psychological and physical symptoms by the included guidelines. However, significant variations in the level of evidence and grade of recommendation were identified among the included CPGs. Conclusion: Recommendations for the self-managed non-pharmacological interventions were varied and limited among the 14 CPGs, and some were based on medium- and low-quality evidence. More rigorous methods are required to develop high-quality CPGs to guide clinicians in offering high-quality and tailored breast cancer survivorship care.