Selection and evaluation of quality markers (Q-markers) of vladimiriae radix extract for cholestatic liver injury based on spectrum-effect relationship, pharmacokinetics, and molecular docking.

ETHNOPHARMACOLOGICAL RELEVANCE: As a representative local medicinal herb produced in China, Vladimiriae Radix (VR) has been proven to exert hepatoprotective and choleretic effects, with particular therapeutic efficacy in cholestatic liver injury (CLI), as demonstrated by the VR extract (VRE). However, the quality markers (Q-markers) of VRE for the treatment of CLI remain unclear. AIM OF THE STUDY: A new strategy based on the core element of "efficacy" was proposed, using a combination of spectrum-effect relationship, pharmacokinetics, and molecular docking methods to select and confirm Q-markers of VRE. MATERIAL AND METHODS: First, the HPLC fingerprinting of 10 batches of VRE was studied, and the in vivo pharmacological index of anti-CLI in rats was determined. The spectrum-effect relationship was utilized as a screening method to identify the Q-markers of VRE. Secondly, Q-markers were used as VRE pharmacokinetic markers to measure their concentrations in normal and CLI rat plasma, and to analyze their disposition. Finally, molecular docking was utilized to predict the potential interaction between the identified Q-markers and crucial targets of CLI. RESULTS: The fingerprints of 10 batches of VRE was established. The in vivo pharmacological evaluation of rats showed that VRE had a significant therapeutic effect on CLI. The spectrum-effect correlation analysis showed that costunolide (COS) and dehydrocostus lactone (DEH) were the Q-markers of VRE anti-CLI. The pharmacokinetic results showed that AUC(0-t), Cmax, CLZ/F, and VZ/F of COS and DEH in CLI rats had significant differences (P < 0.01). They were effectively absorbed into the blood plasma of CLI rats, ensuring ideal bioavailability, and confirming their role as Q-markers. Molecular docking results showed that COS, DEH had good affinity with key targets (FXR, CAR, PXR, MAPK, TGR5, NRF2) for CLI treatment (Binding energy < -4.52 kcal mol-1), further verifying the correctness of Q-marker selection. CONCLUSIONS: In this study, through the combination of experimental and theoretical approaches from the aspects of pharmacodynamic expression, in vivo process rules, and interaction force prediction, the therapeutic effect of VRE and Q-markers (COS、DEH) were elucidated. Furthermore, a new idea based on the principle of "efficacy" was successfully proposed for screening and evaluating Q-markers.

Enhancing Tai Chi Training System: Towards Group-Based and Hyper-Realistic Training Experiences.

In this article, we propose a lightweight and flexible enhanced Tai Chi training system composed of multiple standalone virtual reality (VR) devices. The system aims to enable a hyper-realistic multi-user action training platform at low cost by displaying real-time action guidance trajectories, providing real-world impossible visual effects and functions, and rapidly enhancing movement precision and communication interest for learners. We objectively evaluate participants' action quality at different levels of immersion, including traditional coach guidance (TCG), VR, and mixed reality (MR), along with subjective measures like motion sickness, quality of interaction, social meaning, presence/immersion to comprehensively explore the system's feasibility. The results indicate VR performs the best in training accuracy, but MR provides superior social experience and relatively high accuracy. Unlike TCG, MR offers hyper-realistic hand movement trajectories and Tai Chi social references. Compared with VR, MR provides more realistic avatar companions and a safer environment. In summary, MR balances accuracy and social experience.

The interface engineering and structure design of an alloying-type metal foil anode for lithium ion batteries: a review.

An alloying-type metal foil serves as an integrated anode that is distinct from the prevalent powder-casting production of lithium ion batteries (LIBs) and emerging lithium metal batteries (LMBs), and also its energy density and processing technology can be profoundly developed. However, besides their apparent intriguing advantages of a high specific capacity, electrical conductivity, and the ease of formation, metal foil anodes suffer from slow lithiation kinetics, a trade-off between specific capacity and cycle life, and a low initial Coulombic efficiency (ICE) owing to their multi-scaled structural geometry, huge volume change, and induced interfacial issues during the alloying process. In this review, we attempt to present a comprehensive overview on the recent research progress with respect to alloying-type metal foil anodes toward high-energy-density and low-cost LIBs. The failure mechanism of metal foil anodes during lithiation/delithiation and existing challenges are also summarized. Subsequently, the structural design and interface engineering strategies that have witnessed significant achievements are highlighted, which can promote the practical development of LIBs, including artificial SEI, alloying, structural design, and grain refinement. Furthermore, scientific perspectives are proposed to further improve the overall performance and decouple the complex mechanisms in terms of interdisciplinary fields of electrochemistry, metallic materials science, mechanics, and interfacial science, demonstrating that metal foil anode-based LIBs require more research efforts.

Synergistic effect of berberine hydrochloride and dehydrocostus lactone in the treatment of ulcerative colitis: Take gut microbiota as the target.

Ulcerative colitis (UC) is a difficult-to-cure and recurrent inflammatory bowel disease, and it is difficult to maintain long-term results with a single drug. Inspired by clinical medication in traditional Chinese medicine, we used berberine hydrochloride (BBH) and dehydrocostus lactone (DEH) in combination for the first time and focused on studying their mechanism of treating UC based on gut microbiota. Therefore, we evaluated the therapeutic effects of BBH and DEH on DSS-induced UC mice using ELISA, HE and AB-PAS staining, 16s rDNA amplicon sequencing technology, and fecal transplantation experiments (FMT). In this study, the combination of BBH and DEH significantly relieved symptoms, colonic inflammation, and intestinal barrier damage of DSS-induced UC mice, and they did not show antagonism. In addition, the co-administration of BBH and DEH altered the composition and function of gut microbiota, with BBH increasing the abundance of key beneficial bacterial genus Akkermansia and DEH aiming to enhance species diversity and supplying intestinal proteins to prevent overconsumption. Furthermore, our data showed that BBH and DEH improve the levels of short-chain fatty acids, which also proved the positive regulation of gut microbiota by BBH and DEH. Finally, the FMT confirmed the strong correlation between BBH, DEH, and the gut microbiota. In conclusion, the co-administration of BBH and DEH protected the intestinal barrier and reduced inflammatory damage by regulating gut microbiota, targeting the key beneficial bacterial genus Akkermansia, and maintaining a normal supply of intestinal proteins.

Efficient remediation of soils contaminated with petroleum hydrocarbons using sustainable plant-derived surfactants.

Surfactant-enhanced multiphase extraction is recognized as an effective method to remove petroleum related contaminants from soil. Owing to the high biodegradability and low biotoxicity, plant-derived surfactants are considered as promising alternatives to synthetic surfactants. In this study, two plant surfactants were respectively extracted from Sapindus mukorossi (PS-1) and Fructus Gleditsiae sinensis (PS-2). Component analysis and chemical structure characterization indicated that triterpenoid saponins were the main components of both plant surfactants. The removal efficiency of tetradecane by PS-1 and PS-2 was 75.6% and 62.2%, respectively, which was comparable with that by Tween-80. The results were validated by column leaching experiments. The abundant hydroxyl, aldehyde and epoxy groups in the plant surfactants made them readily self-assemble to form micelles via hydrogen bonding and van der Waals interactions, which promoted the solubilization of tetradecane in the liquid phase, particularly at appropriate ionic strength and temperature. Due to the reduced electrostatic attraction by the acidic and ionizable functional groups in the plant surfactants, their sorption capacities (0.15 and 0.24 g1-n Ln·kg-1 for PS-1 and PS-2, respectively) onto the soil were much lower than that of Tween-80, making them much easier to be extracted from contaminated soil. This study would deepen our understanding to improve the performances of plant surfactants in petroleum hydrocarbons-contaminated soil remediation.

Evaluating a WeChat-Based Health Behavioral Digital Intervention for Patients With Hypertension: Protocol for a Randomized Controlled Trial.

BACKGROUND: Hypertension is the most prevalent chronic condition and a significant risk factor for cardiovascular and kidney diseases. The efficacy of health behavioral interventions in blood pressure (BP) control has been demonstrated by a large and expanding body of literature, with "adherence" playing a crucial role. WeChat is the most common social communication mobile app in China, and it has been shown to be an acceptable delivery platform for delivering health interventions. The WeChat-based health behavioral digital intervention program (WHBDIP) showed high feasibility and efficacy. However, the results regarding BP improvement between the WHBDIP and control groups were inconsistent. OBJECTIVE: The objective of this study is to develop a WHBDIP and assess its efficacy in controlling BP and improving adherence among patients with hypertension. METHODS: A 2-arm, parallel-group, and randomized trial design was used. Patients older than 60 years and with hypertension were randomly assigned to either the control group or the experimental group, which received a 12-week intervention. The program, primarily developed based on the Behavior Change Wheel (BCW) theory, offers health education on exercise, diet, BP monitoring, and medicine adherence (MA). It also includes other behavior interventions guided by an intervention manual, incorporating behavior change techniques (BCTs). The primary outcomes encompass BP and adherence indicators, while the secondary outcomes encompass cardiovascular function indicators, body composition indicators, learning performance, satisfaction, and acceptability. The exercise and blood pressure monitoring adherence (BPMA) indicators for the WHBDIP group were assessed weekly via WeChat during the initial 3 months, while other outcome data for both groups will be collected at the baseline assessment phase, 3 months after the intervention, and 1 year after the program. RESULTS: The trial will assess the efficacy of WHBDIP for patients with hypertension (N=68). The WHBDIP seeks to enhance participants' knowledge of healthy behaviors and assist patients in developing positive health behaviors to improve their health outcomes. Patient recruitment for individuals with hypertension commenced on September 5, 2022, and concluded on September 19, 2022. The 3-month intervention and phased data collection were finalized in January 2023. Data analysis will commence in August 2023, and the final 1-year health outcome results will be collected in September 2023. CONCLUSIONS: A successful WHBDIP will establish the management mode as a feasible approach for hypertension management in the community. Additionally, it will pave the way for the development of related mobile health programs. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200062643; https://tinyurl.com/mwyv67wk. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/46883.

Intrinsic mechanisms for the inhibition effect of graphene oxide on the catalysis activity of alpha amylase.

Comprehending the interactions between graphene oxide (GO) and enzymes is critical for understanding the toxicities of GO. In this study, the inherent interactions of GO with α-amylase as a typical enzyme, and the impacts of GO on the conformation and biological activities of α-amylase were systematically investigated. The results reveal that GO formed ground-state complex with α-amylase primarily via hydrogen bonding and van der Waals interactions, thus quenching the intrinsic fluorescence of the protein statically. Particularly, the strong interactions altered the microenvironment of tyrosine and tryptophan residues, caused rearrangement of polypeptide structure, and reduced the contents of α-helices and ß-sheets, thus changing the conformational structure of α-amylase. According to molecular docking results, GO binds with the amino acid residues (i.e., His299, Asp300, and His305) of α-amylase mainly through hydrogen bonding, which is in accordance with in vitro incubation experiments. As a consequence, the ability of α-amylase to catalyze starch hydrolysis into glucose was depressed by GO, suggesting that GO might cause dysfunction of α-amylase. This study discloses the intrinsic binding mechanisms of GO with α-amylase and provides novel insights into the adverse effects of GO as it enters organisms.

Polygonati Rhizoma with the homology of medicine and food: A review of ethnopharmacology, botany, phytochemistry, pharmacology and applications.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygonati Rhizoma (PR), which contains rich national cultural connotations, is a traditional Chinese medicine with homology of medicine and food. It has been used for a long time as a tonic in China's multi-ethnic medical system, and is also used to treat diseases such as premature graying hair, deficiency of blood and essence, diabetes, hypertension, etc. Meanwhile, PR is often used as food in China, India, South Korea and other Asian countries, which can satisfy hunger and provide many health benefits. AIM OF THE REVIEW: This paper systematically reviewed the ethnopharmacology, botany, phytochemistry, pharmacology and related applications research of PR, and provided a reference for the comprehensive applications of PR, including basic research, product development and clinical applications. This paper also refined the national application characteristics of PR, such as rich plant resources, special chemical components and anti-hidden hungry, which laid a foundation for its high value and high connotation development in the future. MATERIALS AND METHODS: The literature information was collected systematically from the electronic scientific databases, including PubMed, Science Direct, Google Scholar, Web of Science, Geen Medical, China National Knowledge Infrastructure, as well as other literature sources, such as classic books of herbal medicine. RESULTS: A comprehensive analysis of the above literature confirmed that PR has been used in the ethnic medicine system of Asian countries such as China for thousands of years. In this paper, 12 species including official species that can be used as PR are summarized, which provide rich plant resources for PR. The chemical components in PR are divided into nutritional components and active components. The former not only contains non-starch polysaccharides and fructo-oligosaccharides, which account for about 50% in PR and are recognized as high-quality diet in the world, but also contains inorganic elements and mineral elements. And a total of 199 kinds active ingredients, including saponins, flavonoids, alkaloids, etc., were sorted out by us. The above ingredients make PR have a special property of anti-hidden hunger. Studies have shown that PR has a wide range of pharmacological activities, such as immune regulation, blood glucose regulation, lipid-lowering, antioxidant, anti-tumor, antibacterial, etc. It has been widely used in medicine, food, cosmetics, gardens and other fields. CONCLUSIONS: PR, as a classic medicinal material of the same origin, is widely used in the traditional ethnic medicine system. It contains abundant potential plant resources, chemical components and pharmacological activities. This paper also suggests that PR with high application value in food industry, has the potential to become a high-quality coarse grain. Exploring the way of grain and industrialization of PR is beneficial to fully develop the economic value of PR.

YEATS2 regulates the activation of TAK1/NF-κB pathway and is critical for pancreatic ductal adenocarcinoma cell survival.

The prognosis of pancreatic ductal adenocarcinoma (PDAC) is poor despite diagnostic progress and new chemotherapeutic regimens. Constitutive activation of NF-κB is frequently observed in PDAC. In this study, we found that YEATS2, a scaffolding protein of ATAC complex, was highly expressed in human PDAC. Depletion of YEATS2 reduced the growth, survival, and tumorigenesis of PDAC cells. The binding of YEATS2 is crucial for maintaining TAK1 activation and NF-κB transcriptional activity. Of importance, our results reveal that YEATS2 promotes NF-κB transcriptional activity through modulating TAK1 abundance and directly interacting with NF-κB as a co-transcriptional factor.

Circular RNAs as diagnostic biomarkers for gastric cancer: A comprehensive update from emerging functions to clinical significances.

The incidence and mortality of gastric cancer ranks as a fouth leading cause of cancer death worldwide, especially in East Asia. Due to the lack of specific early-stage symptoms, the majority of patients in most developing nations are diagnosed at an advanced stage. Therefore, it is urgent to find more sensitive and reliable biomarkers for gastric cancer screening and diagnosis. Circular RNAs (circRNAs), a novel type of RNAs with covalently closed loops, are becoming a latest hot spot in the field of. In recent years, a great deal of research has demonstrated that abnormal expression of circRNAs was associated with the development of gastric cancer, and suggested that circRNA might serve as a potential biomarker for gastric cancer diagnosis. In this review, we summarize the structural characteristics, formation mechanism and biological function of circRNAs, and elucidate research progress and existing problems in early screening of gastric cancer.

Limonin, an AMPK Activator, Inhibits Hepatic Lipid Accumulation in High Fat Diet Fed Mice.

NAFLD is the most prevalent liver disease in human history. The treatment is still limited yet. In the current study, we reported that limonin inhibited hepatic lipid accumulation and fatty acid synthesis in HFD fed mice. Using AMPK inhibitor and AMPK deficient C. elegans, we revealed the effect was dependent on the activation of AMPK. We found that limonin activated AMPK through inhibition of cellular energy metabolism and increasing ADP:ATP ratio. Furthermore, the treatment of limonin induced AMPK mediated suppression of the transcriptional activity of SREBP1/2. Our study suggests that limonin may a promising therapeutic agent for the treatment of NAFLD.

A randomized trial on the application of a nurse-led early rehabilitation program after minimally invasive lumbar internal fixation.

BACKGROUND: Lumbar degenerative disease (LDD) is a narrowing of the spinal canal and intervertebral foramina caused by aging and degeneration of lumbar spine tissue. Minimally invasive internal lumbar spine fixation is emerging in the treatment of LDD. However, no standard early rehabilitation protocol for orthopedic robot-assisted minimally invasive internal lumbar spine fixation exits. To investigate the effect of a nurse-led early rehabilitation program in the postoperative recovery of patients with lumbar degenerative lesions undergoing orthopedic robot-assisted minimally invasive lumbar internal fixation. METHODS: Eighty patients with minimally invasive orthopedic robot-assisted lumbar degenerative lesions admitted to our hospital between January 2019 and January 2021 were recruited to this study. The patients were randomly allocated to a control group (n=40), involving conventional care, and an observation group (n=38; 40 initially and 2 later excluded) including a nurse-led early rehabilitation program added on the basis of the control group. The primary outcomes were the general postoperative conditions, scores of daily living ability, the degree of low back pain and functional recovery. Participants were also compared in terms of their compliance with the care regimen and the incidence of complications. RESULTS: Participants in the observation group had a significantly shorter first time on the floor after surgery (P<0.001) and shorter hospital stay (P=0.003). Meanwhile, participants in the observation group had higher Barthel index (BI) scores (P=0.039), lower visual analogue scale (VAS) scores (P=0.028), and Oswestry disability index (ODI) scores (P=0.002) at 3 days postoperatively, and there was no difference in the three scores between the two groups at 1 month postoperatively (all P>0.05). The compliance of participants in the observation group was significantly higher than that of the control group (P<0.001). Participants in the observation group were less likely to experience constipation (P=0.043) and bloating (P=0.012) within 1 month after surgery. CONCLUSIONS: Implementation of a nurse-led early rehabilitation program in patients undergoing orthopedic robotic-assisted minimally invasive treatment of lumbar degenerative lesions can significantly improve patient compliance, significantly shorten postoperative flooring and hospitalization time, reduce the incidence of gastrointestinal adverse events, and accelerate postoperative recovery. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100048698.

Primary Hyperoxaluria Type 1 Disease Manifestations and Healthcare Utilization: A Multi-Country, Online, Chart Review Study.

Background: Primary hyperoxaluria type 1 (PH1) is a rare genetic disease that can result in irreversible damage to the kidneys and, eventually, extrarenal organs. While kidney failure is a known consequence of PH1, few studies to date have characterized clinical consequences of PH1 prior to kidney failure, and data on healthcare resource use outcomes across different stages of disease severity in PH1 are also limited. To help fill this knowledge gap, this study characterized the clinical and healthcare resource use (HRU) burden in patients with PH1 with varying stages of kidney disease. Methods: Nephrologists in the United States, Canada, United Kingdom, France, Germany, and Italy abstracted chart data from patients with PH1 under their care via an online questionnaire. Eligible patients had confirmed PH1 and ≥2 office visits from 2016 to 2019. Results: A total of 120 patients were analyzed (median age at diagnosis, 17.4 years old, median age at index 19.5 years old, median eGFR at index 45 ml/min/1.73 m2; median follow-up 1.7 years). During follow-up, the most common PH1 manifestations were kidney stones and urinary tract infections (UTIs, both 56.8%), and the most common symptoms were fatigue/weakness (71.7%) and pain (64.6%). With regard to HRU during follow-up, 37.4% required lithotripsy, 31.3% required ureteroscopy, and 9.6% required nephrolithotomy. PH1-related hospitalizations and emergency/urgent care visits were noted for 84.0 and 81.6% of patients, respectively. Conclusions: The current study demonstrated that patients with PH1 across various stages of kidney disease exhibited a substantial clinical burden, including kidney stones, UTIs, fatigue/weakness, and pain, and required frequent HRU, including kidney stone procedures, hospitalizations, and emergency visits. These findings highlight the significant morbidity and HRU burden in patients with PH1.

Nobiletin Alleviates Non-alcoholic Steatohepatitis in MCD-Induced Mice by Regulating Macrophage Polarization.

Non-alcoholic steatohepatitis (NASH) is an inflammatory disorder that is characterized by chronic activation of the hepatic inflammatory response and subsequent liver damage. The regulation of macrophage polarization in liver is closely related to the progression of NASH. The orphan nuclear receptor retinoic-acid-related orphan receptor α (RORα) and Krüppel-like factor 4 (KLF4) are key regulators which promote hepatic macrophages toward M2 phenotype and protect against NASH in mice. Nobiletin (NOB), a natural polymethoxylated flavone, is previously reported as a RORα regulator in diet-induced obese mice. However, it is still unclear whether NOB has the protective effect on NASH. In this study, we investigated the role of NOB in NASH using a methionine and choline deficient (MCD)-induced NASH mouse model. Our results showed that NOB ameliorated hepatic damage and fibrosis in MCD fed mice. NOB treatment reduced the infiltration of macrophages and neutrophils in the liver in MCD-fed mice. Of importance, NOB significantly increased the proportion of M2 macrophages and the expression of anti-inflammatory factors in vivo and in vitro. Meanwhile, NOB also decreased the population of M1 macrophages and the expression of proinflammatory cytokines. Mechanistically, NOB elevated KLF4 expression in macrophages. Inhibition of KLF4 abolished NOB regulated macrophage polarization. Furthermore, the regulation of NOB in KLF4 expression was dependent on RORα.