Identification of bioactive compounds and inhibitory effects of TNF-α and COX-2 in the extract from cultured three-spot seahorse (H. trimaculatus).

Three-spot seahorse (Hippocampus trimaculatus) has been consumed as traditional Chinese medicine in Asian society. This study was designed to analyze the bioactive compounds of the solvent extracts from cultured three-spot seahorse by high pressure liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC-ESI/MS/MS). Subsequently, their biological activities were evaluated and confirmed by cell modes and Western blot analysis. Experimental results indicated that taurine and arginine were the primary bioactive compounds identified and quantified without pre- or post-column derivatization within 20 min retention time. The analytical method was established and validated with intraday/interday RSD from 0.25% to 3.34% and with recovery from 87.8% to 91.2%. As compared to other extracts, water layer extract (WLE) contained the most taurine and arginine contents of 6.807 and 0.437 mg/g (dry basis), respectively. In the meanwhile, WLE also showed anti-inflammatory activity on LPS-induced NO production and inhibited the protein expression of TNF-α and COX-2 by Western blot analysis with better cell viability.

Root microbiota of tea plants regulate nitrogen homeostasis and theanine synthesis to influence tea quality.

The flavor profile of tea is influenced not only by different tea varieties but also by the surrounding soil environment. Recent studies have indicated the regulatory role of soil microbes residing in plant roots in nutrient uptake and metabolism. However, the impact of this regulatory mechanism on tea quality remains unclear. In this study, we showed that a consortium of microbes isolated from tea roots enhanced ammonia uptake and facilitated the synthesis of theanine, a key determinant of tea taste. Variations were observed in the composition of microbial populations colonizing tea roots and the rhizosphere across different seasons and tea varieties. By comparing the root microorganisms of the high-theanine tea variety Rougui with the low-theanine variety Maoxie, we identified a specific group of microbes that potentially modulate nitrogen metabolism, subsequently influencing the theanine levels in tea. Furthermore, we constructed a synthetic microbial community (SynCom) mirroring the microbe population composition found in Rougui roots. Remarkably, applying SynCom resulted in a significant increase in the theanine content of tea plants and imparted greater tolerance to nitrogen deficiency in Arabidopsis. Our study provides compelling evidence supporting the use of root microorganisms as functional microbial fertilizers to enhance tea quality.

Purple Napiergrass (Pennisetum purpureum Schumach) Hot Water Extracts Ameliorate High-Fat Diet-Induced Obesity and Metabolic Disorders in Mice.

Purple Pennisetum (Pennisetum purpureum Schumach), a hybrid between Taihucao No. 2 and the local wild species of purple Pennisetum, has dark red stems and leaves due to its anthocyanin content. This study explores the potential of purple napiergrass extracts (PNE) in alleviating obesity and metabolic disorders induced by a high-fat diet in mice, where 50% of the caloric content is derived from fat. Mice were orally administered low-dose or high-dose PNE alongside a high-fat diet. Experimental findings indicate that PNE attenuated weight gain, reduced liver, and adipose tissue weight, and lowered blood cholesterol, triglyceride, low-density lipoprotein, and blood sugar levels. Stained sections showed that PNE inhibited lipid accumulation and fat hypertrophy in the liver. Immunoblotting analysis suggested that PNE improved the inflammatory response associated with obesity, dyslipidemia, and hyperglycemia induced by a high-fat diet. Furthermore, PNE potentially functions as a PPAR-γ agonist, increasing the adiponectin (ADIPOQ) concentration and suppressing inflammatory factors, while elevating the anti-inflammatory factor interleukin-10 (IL-10) in the liver. PNE-treated mice showed enhanced activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) and AMP-activated protein kinase (AMPK) pathways and increased fatty acid oxidation and liver lipolysis. In conclusion, this study elucidated the mechanisms underlying the anti-inflammatory, PI3K/Akt, and AMPK pathways in a high-fat diet-induced obesity model. These findings highlight the potential of PNE in reducing weight, inhibiting inflammation, and improving blood sugar and lipid levels, showing the potential for addressing obesity-related metabolic disorders in humans.

Phellinus linteus mycelia extract in COVID-19 prevention and identification of its key metabolic compounds profiling using UPLC-QTOF-MS/MS spectrometry.

For centuries, food, herbal medicines, and natural products have been valuable resources for discovering novel antiviral drugs, uncovering new structure-activity relationships, and developing effective strategies to prevent/treat viral infections. One such resource is Phellinus linteus, a mushroom used in folk medicine in Taiwan, Japan, Korea, and China. In this rich historical context, the key metabolites of Phellinus linteus mycelia ethanolic extract (GKPL) impacting the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at multiple stages have yet to be explored. Thus, this study systematically identifies and assesses the inhibitory effect of GKPL on the SARS-CoV-2 virus. Initially, the concentrations and contact times of GKPL against SARS-CoV-2 pseudovirus were assessed in HepG2 cells. Subsequently, utilizing the Ultra Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry method, potential biomarkers in the fungal extract were discerned. Metabolomic analysis identified 18 compounds in GKPL, with hispidin and hypholomine B present in the highest amounts. These compounds were isolated using chromatographic techniques and further identified through 1D NMR spectroscopic and mass spectrometry analysis. Hispidin and hypholomine B were found to inhibit the infection of SARS-CoV-2 pseudovirus by reducing angiotensin-converting enzyme 2 gene expression in HepG2, thereby decreasing viral entry. Moreover, hispidin and hypholomine B effectively block the spike receptor-binding domain, while hypholomine B, for the first time, showed significant inhibition of 3CL protease. This suggests that GKPL, enriched with hispidin and hypholomine B, has the potential to be used as an active ingredient against SARS-CoV-2.

Agricultural non-point source pollution and rural transformation in a plain river network: Insights from Jiaxing city, China.

Recently, agricultural non-point source pollution (ANPSP) has gained increasing attention in China. However, using a uniform paradigm to analyze ANPSP in all regions is difficult, considering their geographical, economic, and policy differences. In this study, we adopted the inventory analysis method to estimate the ANPSP of Jiaxing City, Zhejiang Province as a representative region of the plain river network area from 2001 to 2020 and analyzed it in the framework of policies and rural transformation development (RTD). The ANPSP showed an overall decreasing trend over 20 years. Compared to 2001, total nitrogen (TN), total phosphorus (TP), and chemical oxygen demand (COD) decreased by 33.93%, 25.77%, and 43.94%, respectively, in 2020. COD accounted for the largest annual average (67.02%), whereas TP contributed the most to the equivalent emissions (50.9%). The highest contribution of TN, TP, and COD, which fluctuated and decreased over the past 20 years, originated from livestock and poultry farming. However, the contribution of TN and TP from aquaculture increased. The overall trend of RTD and ANPSP showed an inverted "U" shape with time, and the evolution of both showed similar stage characteristics. With the gradual stabilization of RTD, ANPSP successively went through three stages: high-level stabilization (2001-2009), rapid-decreasing (2010-2014), and low-level stabilization (2015-2020). Additionally, the relationships between pollution loads from different agricultural sources and indicators of different dimensions of RTD varied. These findings provide a reference for the governance and planning of ANPSP in the plain river network area and a new perspective for investigating the relationship between rural development and the environment.

Complex components of Shengmai formula interact with organic cation transporter 2 (OCT2) in MDCK cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Shengmai formula (SMF) is a well-known Chinese herbal compound preparation, which is utilized extensively for the treatment of myocardial ischemia, arrhythmia and other life-threatening conditions. Our previous researches have shown that some of the active ingredients in SMF can interact with organic anion transport polypeptide 1B1 (OATP1B1), breast cancer resistance protein (BCRP) and organic anion transporter 1 (OAT1), etc. Organic cation transporter 2 (OCT2) is a highly expressed uptake transporter in the kidney, and its interaction with the major active components in SMF remains unclear. AIM OF THE STUDY: We purposed to explore OCT2-mediated interactions and compatibility mechanisms of the main active compounds in SMF. MATERIALS AND METHODS: Fifteen active ingredients of SMF, including ginsenoside Rb1, Rd, Re, Rg1, Rf, Ro and Rc, methylophiopogonanone A and B, ophiopogonin D and D', schizandrin A and B, schizandrol A and B, were selected to investigate OCT2-mediated interactions in Madin-Darby cacine kidney (MDCK) cells stably expressing OCT2. RESULTS: Among the above 15 main active components, only ginsenosides Rd, Re and schizandrin B could significantly inhibit the uptake of 4-(4-(dimethylamino)styryl)-N-methyl pyridiniumiodide (ASP+), a classical substrate of OCT2. Ginsenoside Rb1 and methylophiopogonanone A can be transported by MDCK-OCT2 cells, and their uptake was significantly reduced when OCT2 inhibitor decynium-22 was added. Ginsenoside Rd could remarkably reduce the uptake of methylophiopogonanone A and ginsenoside Rb1 by OCT2, ginsenoside Re only decreased the uptake of ginsenoside Rb1, while schizandrin B had no effect on the uptake of both. CONCLUSIONS: OCT2 mediates the interaction of the major active components in SMF. Ginsenosides Rd, Re and schizandrin B are the potential inhibitors of OCT2, while ginsenosides Rb1 and methylophiopogonanone A are the potential substrates of OCT2. There is an OCT2-mediated compatibility mechanism among these active ingredients of SMF.

HIV/AIDS Curability Study, Different Approaches and Drug Combination.

AIM: HIV infection is currently an incurable disease characterized by life-long drug utility. Its incurable causality and mechanism are still unknown to us. METHODS: To overcome this therapeutic setback, some breakthroughs should be made by utilizing different approaches. How to plan some experimental and clinical novelty for HIV curability is a modern challenge. In this article, new ideas and approaches for global HIV/AIDS therapeutic strategies are proposed and represented by scientific insights. RESULTS: Pharmaceutical characteristics, herbal medicine, novel drug targets, cutting-edge biotherapy, drug combination, animal modalities, and immune-stimuli for HIV latency, as well as clearance, are highlighted. DISCUSSION: To elucidate our understanding of curative treatment for HIV/AIDS, many new pathological discoveries, expansion, technical advances, and potential drug targets are constructed. After the discovery of novel pathogenesis and therapeutic evolution, HIV/AIDS therapeutic curability may become achievable and a reality. CONCLUSION: Transformation from animal model investigation to widespread therapies for larger volume of human population is a necessity in modern medicine. In this infectious treatment scenario, major breakthroughs in medicine and drug development are anticipated.

Effect of hot water extracts of Arthrospira maxima (spirulina) against respiratory syncytial virus.

BACKGROUND: Spirulina (Arthrospira maxima) hot water extracts such as calcium spirulan (Ca-SP) have demonstrated antiviral effects against herpes simplex virus (HSV), human immunodeficiency virus-1 (HIV-1), and influenza virus infections. There is no prior evidence suggesting the anti-viral activity of the spirulina hot water extract against respiratory syncytial virus (RSV). PURPOSE: There are currently no effective antivirals available to treat RSV infection. Therefore, the development of safe and novel anti-RSV drugs is urgent and necessary. The aim of this work was to demonstrate the anti-RSV activity of spirulina hot water extracts and determine the potential mechanism of action. METHODS: Cytotoxicity and anti-RSV activity of spirulina hot water extracts were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and neutralization assays, respectively. Potential mechanisms and components were assessed using time of addition, attachment, internalization, pull-down assays, and composition analysis. RESULTS: The polysaccharide-enriched high-molecular weight fraction (>100 kDa, SHD1) had a high total sugar content, with rhamnose accounting for approximately 60 mol% of total monosaccharides. The main glycosyl linkages included 3-, 4-, and 2,3-rhamnopyranosyl linkages. All spirulina hot water extracts showed no toxicity toward human epithelial type 2 (HEp-2) cells but demonstrated anti-RSV activity. The SHD1 had a half maximal effective concentration (EC50) of 0.0915 mg/ml and a selective index (SI) of >261.5 against RSV. SHD1 significantly reduced viral yield in a dose-dependent manner during the RSV attachment stage. SHD1 disrupted RSV internalization and inhibited RSV attachment (G) protein binding to heparan sulfate receptors on the host cell surface, thus preventing RSV attachment and entry. CONCLUSION: SHD1 serves as an effective candidate for novel drug development against RSV infection.

Human induced pluripotent stem cell (hiPSC)-derived cardiomyocyte modelling of cardiovascular diseases for natural compound discovery.

Cardiovascular disease (CVD) remains the leading cause of death worldwide. Natural compounds extracted from medicinal plants characterized by diverse biological activities and low toxicity or side effects, are increasingly taking center stage in the search for new drugs. Currently, preclinical evaluation of natural products relies mainly on the use of immortalized cell lines of human origin or animal models. Increasing evidence indicates that cardiomyopathy models based on immortalized cell lines do not recapitulate pathogenic phenotypes accurately and a substantial physiological discrepancy between animals and humans casts doubt on the clinical relevance of animal models for these studies. The newly developed human induced pluripotent stem cell (hiPSC) technology in combination with highly-efficient cardiomyocyte differentiation methods provides an ideal tool for modeling human cardiomyopathies in vitro. Screening of drugs, especially screening of natural products, based on these models has been widely used and has shown that evaluation in such models can recapitulate important aspects of the physiological properties of drugs. The purpose of this review is to provide information on the latest developments in this area of research and to help researchers perform screening of natural products using the hiPSC-CM platform.

A systematic, complexity-reduction approach to dissect the kombucha tea microbiome.

One defining goal of microbiome research is to uncover mechanistic causation that dictates the emergence of structural and functional traits of microbiomes. However, the extraordinary degree of ecosystem complexity has hampered the realization of the goal. Here, we developed a systematic, complexity-reducing strategy to mechanistically elucidate the compositional and metabolic characteristics of microbiome by using the kombucha tea microbiome as an example. The strategy centered around a two-species core that was abstracted from but recapitulated the native counterpart. The core was convergent in its composition, coordinated on temporal metabolic patterns, and capable for pellicle formation. Controlled fermentations uncovered the drivers of these characteristics, which were also demonstrated translatable to provide insights into the properties of communities with increased complexity and altered conditions. This work unravels the pattern and process underlying the kombucha tea microbiome, providing a potential conceptual framework for mechanistic investigation of microbiome behaviors.

Drug Sensitivity Testing for Cancer Therapy, Key Areas.

AIMS: Cancer is a high-mortality disease (9.6 million deaths in 2018 worldwide). Given various anticancer drugs, drug selection plays a key role in patient survival in clinical trials. METHODS: Drug Sensitivity Testing (DST), one of the leading drug selective systems, was widely practiced for therapeutic promotion in the clinic. Notably, DSTs assist in drug selection that benefits drug responses against cancer from 20-22% to 30-35% over the past two decades. The relationship between drug resistance in vitro and drug treatment benefits was associated with different tumor origins and subtypes. Medical theory and underlying DST mechanisms remain poorly understood until now. The study of the clinical scenario, sustainability and financial support for mechanism and technical promotions is indispensable. RESULTS: Despite the great technical advance, therapeutic prediction and drug selection by DST needs to be miniature, versatility and cost-effective in the clinic. Multi-parameters and automation of DST should be a future trend. Advanced biomedical knowledge and clinical approaches to translating oncologic profiles into drug selection were the main focuses of DST developments. With a great technical stride, the clinical architecture of the DST platform was entering higher levels (drug response testing at any stage of cancer patients and miniaturization of tumor samples). DISCUSSION: The cancer biology and pharmacology for drug selection mutually benefit the clinic. New proposals to reveal more therapeutic information and drug response prediction at genetic, molecular and omics levels should be estimated overall. CONCLUSION: By upholding this goal of non-invasive, versatility and automation, DST could save the life of several thousand annually worldwide. In this article, new insights into DST novelty and development are highlighted.

Press tack needle stimulation for blunt chest trauma: a randomized double-blind control trial.

OBJECTIVES: Blunt chest trauma is often associated with severe pain, reduced lung function and decreased sleep quality. This study aims to investigate the immediate and long-term effect of acupuncture on these factors using a randomized control double-blind design. METHODS: A total of 72 patients were randomized into 2 groups: treatment group (press tack acupuncture) and control group (press tack placebo). The face rating scale, numerical rating scale (NRS), portable incentive spirometer and Verran Snyder-Halpern sleep scale were measured at baseline, immediately after the intervention, and at the 4th day, with 2-weeks and 3-months follow-ups. RESULTS: There were no significant changes between the groups at the baseline measurements, with the exception of hypertension comorbidity. Immediately after the intervention and on the 4th day follow-up, the patients in the treatment group showed a significantly lower face rating scale when compared to the control (P < 0.05). There were no significant changes in any of the other measurements between the groups (P > 0.05). Subgroup analysis revealed that the NRS for turn over on the 4th day was reduced significantly in the treatment group of patients without lung contusion (P < 0.05). For patients without pleural drainage, cough NRS in the treatment group was significantly reduced in the 2-week follow-up (P < 0.05). CONCLUSIONS: This study showed that press tack acupuncture effects on pain reduction were inconclusive. However, future studies on the effect of acupuncture on blunt chest trauma patients are needed. CLINICAL TRIAL REGISTRATION: clinicaltirl.gov: NCT04318496.

Reporting and methodological quality of meta-analyses of acupuncture for patients with migraine: A methodological investigation with evidence map.

BACKGROUND: Acupuncture has been widely used to relieve migraine-related symptoms. However, the findings of previous systematic reviews (SRs) and meta-analyses (MAs) are still not completely consistent. Their quality is also unknown, so a comprehensive study is needed. OBJECTIVE: To evaluate the reporting and methodological quality of these MAs concerning acupuncture for migraine, and summarize evidence about the efficacy and safety of acupuncture for migraine. SEARCH STRATEGY: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Databases, Wanfang Data, and VIP databases were searched from inception to September 2020, with a comprehensive search strategy. INCLUSION CRITERIA: The pairwise MAs of randomized controlled trials (RCTs) concerning migraine treated by acupuncture or acupuncture-based therapies, with a control group that received sham acupuncture, medication, no treatment, or acupuncture at different acupoints were included. DATA EXTRACTION AND ANALYSIS: Two independent investigators screened studies, extracted relevant data, and assessed reporting and methodological quality using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2009 and A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2), then all results were cross-checked. Spearman correlation test was used to evaluate the correlation between reporting and methodological quality scores. RESULTS: A total of 20 MAs were included in this study. The included MAs indicated that acupuncture was efficacious and safe in preventing and treating migraine when compared with control intervention. There was a high correlation between reporting and methodological quality scores (rs = 0.87, P < 0.001). The quality of the included SRs needs to be improved mainly with regard to protocol and prospective registration, using a comprehensive search strategy, summarizing the strength of evidence body for key outcomes, a full list of excluded studies with reasons for exclusion, reporting of RCTs' funding sources, and assessing the potential impact of risk of bias in RCTs on MA results. CONCLUSION: Acupuncture is an effective and safe intervention for preventing and treating migraine, and could be considered as a good option for patients with migraine. However, the reporting and methodological quality of MAs included in this overview is suboptimal. In the future, AMSTAR 2 and PRISMA tools should be followed when making and reporting an SR with MA.

Omega-3 fatty acids and blood-based biomarkers in Alzheimer's disease and mild cognitive impairment: A randomized placebo-controlled trial.

BACKGROUND: Increased serum levels of pro-inflammatory biomarkers are consistently associated with cognitive decline. The omega-3 unsaturated fatty acids (n-3 PUFAs) had been linked to slowing cognitive decline due to their potential anti-inflammatory effects. To our knowledge, the different regiments of pure DHA, pure EPA, and their combination on various associated symptoms of dementia, including a mild form of cognitive impairment (MCI) and Alzheimer's disease (AD), have never been studied. METHODS: This multisite, randomized, double-blind, placebo-controlled trial was conducted at two veteran's retirement centers and one medical center in central Taiwan between 2013 and 2015. 163 MCI or AD patients were randomly assigned to placebo (n = 40), docosahexaenoic acid (DHA, 0.7 g/day, n = 41), eicosapentaenoic acid (EPA, 1.6 g/day, n = 40), or EPA (0.8 g/day) + DHA (0.35 g/day) (n = 42) group for 24 months. The results were measured as the cognitive and functional abilities, biochemical, and inflammatory cytokines profiles. Chi-square tests, two-sample t-test, ANOVA, and linear mixedeffects models were conducted with p < 0.05. RESULTS: 131 (80%) participants had completed the trial with all cognitive, functional, and mood status assessments. The statistically significant difference between the placebo and treatment groups was not determined, concerning the changes in cognitive, functional, and mood status scores, the biochemical profiles, and inflammatory cytokines levels. However, EPA was found to reduce the C-C motif ligands 4 (CCL4) level (p < 0.001). Additionally, EPA could reduce the constructional praxis (p < 0.05) and spoken language ability scores (p < 0.01), and DHA also reduced the spoken language ability score (p < 0.05). CONCLUSION: Overall, n-3 PUFAs supplements did not reduce cognitive, functional, and depressive symptom outcomes, but spoken language ability and constructional praxis subitems of ADAS-cog. These findings show that attention to clinical heterogeneity in dementia is crucial when studying nutrients interventions, such as n-3 PUFAs. In addition, with small effect size CCL4 is a better indicator than other inflammatory cytokines for EPA treatment response.

Effectiveness of traditional Chinese medicine in treating gastrointestinal dysfunction in patients with acute stroke: a systematic review and meta-analysis of 16 randomized controlled trials.

BACKGROUND: Gastrointestinal dysfunction is one of the complications after stroke. If it is not treated in time, it will affect the rehabilitation process after stroke and reduce the quality of life of patients. In this study, we conducted a systematic review and meta-analysis of the reports on the treatment of gastrointestinal dysfunction after stroke with traditional Chinese medicine (TCM) in recent years to provide evidence for clinical diagnosis and treatment. METHODS: The clinical randomized controlled trials (RCTs) published in Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Medline, and Web of Science databases from January 2010 to August 2021 were searched. After screening the qualified literatures, literature quality evaluation was performed. The software Stata 16.0 was used to analyze and compare the outcome indicators of TCM and conventional western medicine treatment, and the utility of TCM in the treatment of gastrointestinal disorders after stroke was comprehensively evaluated. RESULTS: A total of 16 studies were finally selected including a total of 1,589. Meta-analysis showed that TCM treatment of gastrointestinal disorders after stroke was more effective than conventional western medicine treatment [odds ratio (OR) =3.94; 95% confidence interval (CI): 2.63 to 5.89; P=0.000]. It was also shown that TCM can reduce the recovery time of bowel sounds and is superior to conventional western medicine [standard mean difference (SMD) =-1.92; 95% CI: -2.51 to -1.34; P=0.000]; reduce defecation and flatulence recovery time (SMD =-2.51; 95% CI: -3.41 to -1.61; P=0.000); increase gastrin level (SMD =0.80; 95% CI: 0.35 to 1.25; P=0.001); increase motilin level (SMD =2.27; 95% CI: 1.55 to 3.00; P=0.000); increase serum albumin level (SMD =0.72; 95% CI: 0.54 to 0.90; P=0.000); increase transferrin levels (SMD =1.11; 95% CI: 0.86 to 1.36; P=0.000); and it can increase serum prealbumin levels (SMD =1.50; 95% CI: 0.78 to 2.22; P=0.000). DISCUSSION: The use of TCM in the treatment of gastrointestinal dysfunction after stroke can effectively reduce symptoms, shorten the recovery time of bowel sounds, the first defecation and flatulence time, promote gastric motility and gastrointestinal hormone secretion, and improve the nutritional status of patients.

Keratin-Based Nanoparticles with Tumor-Targeting and Cascade Catalytic Capabilities for the Combinational Oxidation Phototherapy of Breast Cancer.

Photodynamic therapy (PDT) holds tantalizing prospects of a prominent cancer treatment strategy. However, its efficacy remains limited by virtue of the hypoxic tumor microenvironment and the inadequate tumor-targeted delivery of photosensitizers, and these can be further exacerbated by the lack of development of a well-controlled nitric oxide (NO) release system at the target site. Inspired by Chinese medicine, we propose a revealing new keratin application. Keratin has garnered attention as an NO generator; however, its oncological use has rarely been investigated. We hypothesized that the incorporation of a phenylboronic acid (PBA) targeting ligand/methylene blue (MB) photosensitizer with a keratin NO donor would facilitate precise tumor delivery, enhancing PDT. Herein, we demonstrated that MB@keratin/PBA/d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) nanoparticles (MB@KPTNPs) specifically targeted breast cancer cells and effectively suppressed their growth. Through MB-mediated biometabolism, the endocytic MB@KPTNPs produced a sufficient amount of intracellular NO that reduced the glutathione level while boosting the efficiency of PDT. A therapeutic combination of NO/PDT was therefore achieved, resulting in significant inhibition of both in vivo tumor growth and lung metastasis. These findings underscore the importance of utilizing keratin-based nanoparticles that simultaneously combine targeting of the tumor and self-generating NO with a cascading catalytic ability as a novel oxidation therapeutic strategy for enhancing PDT.

Evaluation of the efficacy of traditional Chinese medicine for the reproductive and pregnancy outcomes in women with endometriosis: A nationwide population-based study.

OBJECTIVE: Patients with endometriosis may seek traditional Chinese medicine (TCM) to help them conceive. The present study aims to evaluate the effects of TCM on reproductive and pregnancy outcomes in patients with endometriosis. MATERIALS AND METHODS: The patients with endometriosis taken from the National Health Insurance (NHI) research database between 2000 and 2012 were divided into two cohorts based on the use of TCM treatment. The two cohorts were matched by age and comorbidities and followed up until a new diagnosis of infertility, ectopic pregnancy, or miscarriage. Multivariable Cox proportional hazards models were used to evaluate the hazard ratio (HR) of reproductive and pregnancy outcomes. RESULTS: A total of 5244 patients with endometriosis were analyzed, including 1748 TCM users and 3496 matched control subjects. The proportion of infertility was higher in TCM users than in non-TCM users (adjusted hazard ratio [HR]: 1.34, 95% confidence interval [CI]: 1.13-1.60). However, there was no significant difference in the proportion of ectopic pregnancies between TCM users and non-TCM users (adjusted HR: 0.82, 95% CI: 0.60-1.13). There was no significant difference in the proportion of miscarriages between TCM users and non-TCM users (adjusted HR: 1.23, 95% CI: 0.95-1.61). CONCLUSION: TCM treatment showed insignificant efficacy in decreasing the risk of ectopic pregnancy and miscarriage in patients with endometriosis.

Acupuncture for blunt chest trauma: A protocol for a double-blind randomized control trial.

INTRODUCTION: Blunt chest trauma (BCT) accounts for up to 65% of polytrauma patients. In patients with 0 to 2 rib fractures, treatment interventions are typically limited to oral analgesics and breathing exercises. Patients suffering from BCT experience symptoms of severe pain, poor sleep, and inability to perform simple daily life activities for an extended period of time thereafter. In this trial, we aim to investigate the efficacy of acupuncture as a functional and reliable treatment option for blunt chest trauma patients. METHODS: The study is designed as a double-blind randomized control trial. We will include 72 patients divided into 2 groups; the acupuncture group (Acu) and placebo group (Con). The acupuncture group will receive true acupuncture using a uniquely designed press tack needle. The control group will receive placebo acupuncture treatment through the use of a similarly designed press tack needle without the needle element. The acupoints selected for both groups are GB 34, GB 36, LI 4, LU 7, ST 36, and TH 5. Both groups will receive 1 treatment only following the initial visit to the medical facility and upon diagnosis of BCT. Patient outcome measurements include: Numerical Rating Scale, Face Rating Scale, respiratory function flowmeter, Verran Snyder-Halpern sleep scale, and the total amount of allopathic medication used. Follow-up time will be scheduled at 4 days, 2 weeks, and lastly 3 months. EXPECTED OUTCOME: The results of this study can potentially provide a simple and cost-effective analgesic solution to blunt chest trauma patients. This novel study design can serve as supporting evidence for future double-blind studies within the field of acupuncture. OTHER INFORMATION: The study will be conducted in the thoracic surgical department and acupuncture department in China Medical University Hospital, Taichung, Taiwan. The study will be conducted on blunt chest trauma patients and is anticipated to have minimum risk of adverse events. Enrollment of the patients and data collection will start from March 2020. Study completion time is expected in March 2022. PROTOCOL REGISTRATION: (CMUH109-REC1-002), (NCT04318496).

Dual-Targeting Glycol Chitosan/Heparin-Decorated Polypyrrole Nanoparticle for Augmented Photothermal Thrombolytic Therapy.

Near-infrared (NIR)-light-modulated photothermal thrombolysis has been investigated to overcome the hemorrhage danger posed by clinical clot-busting substances. A long-standing issue in thrombosis fibrinolytics is the lack of lesion-specific therapy, which should not be ignored. Herein, a novel thrombolysis therapy using photothermal disintegration of a fibrin clot was explored through dual-targeting glycol chitosan/heparin-decorated polypyrrole nanoparticles (GCS-PPY-H NPs) to enhance thrombus delivery and thrombolytic therapeutic efficacy. GCS-PPY-H NPs can target acidic/P-selectin high-expression inflammatory endothelial cells/thrombus sites for initiating lesion-site-specific thrombolysis by hyperthermia using NIR irradiation. A significant fibrin clot-clearance rate was achieved with thrombolysis using dual-targeting/modality photothermal clot disintegration in vivo. The molecular level mechanisms of the developed nanoformulations and interface properties were determined using multiple surface specific analytical techniques, such as particle size distribution, zeta potential, electron microscopy, Fourier-transform infrared spectroscopy (FTIR), wavelength absorbance, photothermal, immunofluorescence, and histology. Owing to the augmented thrombus delivery of GCS-PPY-H NPs and swift treatment time, dual-targeting photothermal clot disintegration as a systematic treatment using GCS-PPY-H NPs can be effectively applied in thrombolysis. This novel approach possesses a promising future for thrombolytic treatment.

Experimental study on static and dynamic mechanical properties of phosphogypsum.

Phosphogypsum (PG) is a solid waste product of the wet-process phosphoric acid industry that accumulates in large amounts on the ground, forming PG ponds. In recent years, the amount of PG produced and discharged into ponds has increased significantly with the increase in the market demand for phosphate fertilizers. To enrich the basic knowledge of PG properties and provide basic data for the stability analysis of PG dams, a series of laboratory geotechnical tests, including permeability tests, compressibility tests, triaxial shear tests, and dynamic triaxial tests, were conducted in this study. During the preparation of the test samples, solubility and high-temperature dehydration of PG were considered. The results indicated that PG exhibits medium compressibility and medium to weak permeability characteristics. The stress-strain curves of the triaxial shear tests were divided into three typical stages: initial deformation stage, strain hardening stage, and destruction stage. With increasing dry density and consolidation confining pressure, both the shear strength and deformation modulus significantly increased. The relationship between the deformation modulus and confining pressure gradually changed from linear to logarithmic with increasing density. The liquefaction resistance curves (CSR-NL curves) of PG were expressed by power functions. With increasing dry density, the curves shifted higher and became steeper. Compared with the Hardin-Drnevich model, the Davidenkov model was found to be more suitable for describing the relationship between the dynamic shear modulus ratio and damping ratio of PG and the dynamic shear strain. Furthermore, compared with those of tailings and natural soils, the engineering mechanical properties of PG were relatively poor, which may be related to its uniform particle distribution and neat particle stacking structure.