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Abstract Background The triglyceride-glucose (TyG) index is linked to both the development and progression of diabetes, while obesity remains a significant risk factor for this disease. However, the relationship between the TyG index and overweight or obese diabetes remains unclear. Methods This study was a cross-sectional analysis of data from 40,633 participants with body mass index (BMI) ≥ 24 kg/m2 who were screened from January 2018 to December 2023 at Henan Provincial People’s Hospital. Participants were divided into groups of overweight or obese individuals with diabetes and those without diabetes according to the diabetes diagnostic criteria. The TyG index, the dependent variable, was determined using the equation ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. We explored the association between TyG index and diabetes in overweight or obese individuals through multivariate logistic regression, subgroup analysis, generalized additive models, smoothed curve fitting, and analysis of threshold effects. Results Patients who were overweight or obese and had diabetes had higher TyG index levels than those without diabetes. After adjusting for confounders, our findings indicated a significant association between the TyG index and the risk of diabetes in overweight or obese individuals [odds ratio (OR) = 7.38, 95% confidence interval (CI): 6.98–7.81]. There was a J-shaped nonlinear association between TyG index and diabetes. When TyG index was > 4.46, the risk of diabetes increased sharply. Notably, a high baseline TyG index (Q4 group) correlated with a notably greater risk of diabetes than did the Q1 group, with an OR of 22.72 (95% CI: 20.52–25.16). Subgroup analysis revealed that the association between TyG and diabetes was stronger in females than in males (OR = 7.57, 95% CI: 6.76–8.48,), more significant in individuals with a BMI of 24–28 kg/m2 than in those with a BMI ≥ 28 kg/m2 (OR = 8.40, 95% CI: 7.83–9.02), and increased with age (OR = 8.15, 95% CI: 7.25–9.17) (all P for interaction 4.46. Furthermore, factors such as sex, age, and BMI significantly influence the risk of diabetes in overweight or obese individuals. Specifically, older women with a BMI of 24–28 kg/m2 are at a greater risk of diabetes under similar TyG index conditions.

Abstract Introduction Chronic inflammation is the major pathological feature of Atherosclerosis(As). Inflammation may accelerate plaque to develop, which is a key factor resulting in the thinning of the fibrous cap and the vulnerable rupture of plaque. Presently, clinical treatments are still lacking. It is necessary to find a safe and effective treatment for As inflammation. Simiaoyongan Decoction (SMYA) has potential anti-inflammatory and plaque protection effects. This protocol aims to evaluate the efficacy, safety, and mechanism of SMYA for patients with carotid atherosclerotic plaque. Methods/design The assessment of SMYA clinical trial is designed as a randomized, double-blind, placebo-controlled study. The sample size is 86 cases in total, with 43 participants in the intervention group and the control group respectively. The intervention group takes SMYA, while the control group takes SMYA placebo. The medication lasts for 14 days every 10 weeks, with a total of 50 weeks. We will use carotid artery high resolution magnetic resonance imaging (HR-MRI) to measure plaque. The plaque minimum fiber cap thickness (PMFCT) is adopted as the primary outcome. The secondary outcomes include plaque fiber cap volume, volume percentage of fiber cap, lipid-rich necrotic core (LRNC) volume, volume percentage of LRNC, internal bleeding volume of plaque, internal bleeding volume percentage of plaque, plaque calcification volume, volume percentage of plaque calcification, lumen stenosis rate, average and a maximum of vessel wall thickness, vessel wall volume, total vessel wall load, carotid atherosclerosis score, hs-CRP, IL-1β and IL-6, the level of lipid profiles and blood glucose, blood pressure, and body weight. Discussion We anticipate that patients with As plaque will be improved from SMYA by inhibiting inflammation to enhance plaque stability. This study analyzes plaque by using HR-MRI to evaluate the clinical efficacy and safety of SMYA. Moreover, we conduct transcriptome analysis, proteomic analysis, and metagenomic analysis of blood and stool of participants to study the mechanism of SMYA against As plaque. This is the first prospective TCM trial to observe and treat As plaque by inhibiting inflammatory reaction directly. If successful, the finding will be valuable in the treatment of As plaque and drug development, especially in the “statin era”. Trial registration number This trial is registered on Chinese Clinical Trials.gov with number ChiCTR2000039062 on October 15, 2020 ( http://www.chictr.org.cn ).

Abstract Reactive astrogliosis is the main cause of secondary injury to the central nerves. Biomaterials can effectively suppress astrocyte activation, but the mechanism remains unclear. Herein, Differentially Expressed Genes (DEGs) are identified through whole transcriptome sequencing in a mouse model of spinal cord injury, revealing the VIM gene as a pivotal regulator in the reactive astrocytes. Moreover, DEGs are predominantly concentrated in the extracellular matrix (ECM). Based on these, 3D injectable electrospun short fibers are constructed to inhibit reactive astrogliosis. Histological staining and functional analysis indicated that fibers with unique 3D network spatial structures can effectively constrain the reactive astrocytes. RNA sequencing and single‐cell sequencing results reveal that short fibers downregulate the expression of the VIM gene in astrocytes by modulating the “ECM receptor interaction” pathway, inhibiting the transcription of downstream Vimentin protein, and thereby effectively suppressing reactive astrogliosis. Additionally, fibers block the binding of Vimentin protein with inflammation‐related proteins, downregulate the NF‐κB signaling pathway, inhibit neuron apoptosis, and consequently promote the recovery of spinal cord neural function. Through mechanism elucidation‐material design‐feedback regulation, this study provides a detailed analysis of the mechanism chain by which short fibers constrain the abnormal spatial expansion of astrocytes and promote spinal cord neural function.

Abstract Background The association between lipid and bone metabolism, particularly the role of high-density lipoprotein cholesterol (HDL-C) in regulating bone mineral density (BMD), is of significant interest. Despite numerous studies, findings on this relationship remain inconclusive, especially since evidence from large, sexually diverse Chinese populations is sparse. This study, therefore, investigates the correlation between HDL-C and lumbar BMD in people of different genders using extensive population-based data from physical examinations conducted in China. Methods Data from a cross-sectional survey involving 20,351 individuals aged > = 20 years drawn from medical records of health check-ups at the Health Management Centre of the Henan Provincial People’s Hospital formed the basis of this study. The primary objective was to determine the correlation between HDL-C levels and lumbar BMD across genders. The analysis methodology included demographic data analysis, one-way ANOVA, subgroup analyses, multifactorial regression equations, smoothed curve fitting, and threshold and saturation effect analyses. Results Multifactorial regression analysis revealed a significant inverse relationship between HDL-C levels and lumbar BMD in both sexes, controlling for potential confounders (Male: β = -8.77, 95% CI -11.65 to -5.88, P 28 kg/m2 and HDL-C > 1.45 mmol/L and in females with a BMI between 24 and 28 kg/m2. Conclusion Elevated HDL-C is associated with decreased bone mass, particularly in obese males. These findings indicate that individuals with high HDL-C levels should receive careful clinical monitoring to mitigate osteoporosis risk. Trial registration The research protocol received ethics approval from the Ethics Committee at Beijing Jishuitan Hospital, in conformity with the Declaration of Helsinki guidelines (No. 2015-12-02). These data are a contribution of the China Health Quantitative CT Big Data Research team, registered at clinicaltrials.gov (code: NCT03699228).

Abstract Malaria poses an enormous threat to human health. With ever increasing resistance to currently deployed drugs, breakthrough compounds with novel mechanisms of action are urgently needed. Here, we explore pyrimidine-based sulfonamides as a new low molecular weight inhibitor class with drug-like physical parameters and a synthetically accessible scaffold. We show that the exemplar, OSM-S-106, has potent activity against parasite cultures, low mammalian cell toxicity and low propensity for resistance development. In vitro evolution of resistance using a slow ramp-up approach pointed to the Plasmodium falciparum cytoplasmic asparaginyl-tRNA synthetase (PfAsnRS) as the target, consistent with our finding that OSM-S-106 inhibits protein translation and activates the amino acid starvation response. Targeted mass spectrometry confirms that OSM-S-106 is a pro-inhibitor and that inhibition of PfAsnRS occurs via enzyme-mediated production of an Asn-OSM-S-106 adduct. Human AsnRS is much less susceptible to this reaction hijacking mechanism. X-ray crystallographic studies of human AsnRS in complex with inhibitor adducts and docking of pro-inhibitors into a model of Asn-tRNA-bound PfAsnRS provide insights into the structure-activity relationship and the selectivity mechanism.

Systematically predicting carbon emissions in the building sector is crucial for formulating effective policies and plans. However, the timing and potential peak emissions from urban buildings remain unclear. This research integrates socio-economic, urban planning, building technology, and energy consumption factors to develop a LEAP-SD model using Shenzhen as a case study. The model considers the interrelationship between socio-economic development and energy consumption, providing more realistic scenario simulations to predict changes in carbon emissions within the urban building sector. The study investigates potential emission peaks and peak times of buildings under different population and building area development scenarios. The results indicate that achieving carbon peaking by 2030 is challenging under a business as usual (BAU) scenario. However, a 10% greater reduction in energy intensity compared to BAU could result in peaking around 2030. The simulation analysis highlights the significant impact of factors such as population growth rate, per capita residential building area, and energy consumption per unit building area and the need for a comprehensive analysis. It provides more realistic scenario simulations that not only enhance theories and models for predicting carbon emissions but also offer valuable insights for policymakers in establishing effective reduction targets and strategies.

Abstract Efferocytosis, an intrinsic regulatory mechanism to eliminate apoptotic cells, will be suppressed due to the delayed apoptosis process in aging‐related diseases, such as osteoarthritis (OA). In this study, cartilage lesion‐localized hydrogel microspheres are developed to remodel the in situ efferocytosis to reverse cartilage senescence and recruit endogenous stem cells to accelerate cartilage repair. Specifically, aldehyde‐ and methacrylic anhydride (MA)‐modified hyaluronic acid hydrogel microspheres (AHM), loaded with pro‐apoptotic liposomes (liposomes encapsulating ABT263, A‐Lipo) and PDGF‐BB, namely A‐Lipo/PAHM, are prepared by microfluidic and photo‐cross‐linking techniques. By a degraded porcine cartilage explant OA model, the in situ cartilage lesion location experiment illustrated that aldehyde‐functionalized microspheres promote affinity for degraded cartilage. In vitro data showed that A‐Lipo induced apoptosis of senescent chondrocytes (Sn‐chondrocytes), which can then be phagocytosed by the efferocytosis of macrophages, and remodeling efferocytosis facilitated the protection of normal chondrocytes and maintained the chondrogenic differentiation capacity of MSCs. In vivo experiments confirmed that hydrogel microspheres localized to cartilage lesion reversed cartilage senescence and promoted cartilage repair in OA. It is believed this in situ efferocytosis remodeling strategy can be of great significance for tissue regeneration in aging‐related diseases.

Abstract Background Traditional Chinese patent medicines (TCPMs) have been widely used to treat carotid atherosclerotic plaque (CAP) in China. However, systematic evaluation of the clinical efficacy of TCPMs for CAP is still unknown, and the comparative efficacy of different TCPMs is unclear. Objectives This study aims to compare and rank the effectiveness and safety of different TCPMs in treating CAP using a Bayesian network meta− analysis (NMA). Methods This NMA was performed according to the Preferred Reporting Items for Systematic Reviews and Meta− Analyses (PRISMA) Extension Statement. Eight databases were searched from their inception to August 2023 for randomized controlled trials (RCTs). The articles regarding eligibility and extracted data were screened independently by two authors. The Cochrane Risk of Bias tool was used to evaluate quality and bias. The change of carotid artery intimal− medial thickness (IMT), carotid maximal plaque area, carotid atherosclerotic plaque Course score, serum lipid levels, CRP, and adverse events rate (AER) were used as outcomes. Data from each RCTs were first pooled using random− effect pairwise meta− analyses and illustrated as odds ratios (ORs) or standardized mean differences (SMDs) with 95% confidence interval (CI). NMAs were performed using Stata17.0 software and the GeMTC package of R software to evaluate the comparative effectiveness of TCPMs, and displayed as ORs or SMDs with 95% CI. A Bayesian hierarchical random− effects model was used to conduct NMAs using the Markov Chain Monte Carlo algorithm. The GRADE partially contextualised framework was applied for NMA result interpretation. Results NMA included 27 RCT trials with 4131 patients and nine types of TCPMs. Pairwise meta− analyses indicated that Conventional Western medicine (CWM) + TCPM was superior to CWM in reducing the IMT (SMD: − 1.26; 95% CI − 1.59 to − 0.93), the carotid maximal plaque area (SMD − 1.27; 95% CI − 1.71, − 0.82) and the carotid atherosclerotic plaque Course score (SMD − 0.72; 95% CI 95% CI − 1.20, − 0.25). NMAs demonstrated that CWM + Jiangzhiling pill (JZL) with SUCRA 70.6% exhibited the highest effective intervention for reducing IMT. CWM + SXBX (Shexiang baoxin pill) was superior to other TCPMs in reducing the carotid maximal plaque area (83.0%), the atherosclerotic plaque Course score (92.5%), TC (95.6%) and LDL (92.6%) levels. CWM + NXT (Naoxintong capsule), CWM + XS (Xiaoshuang granules/enteric capsule), and CWM + ZBT (Zhibitai) were superior to other CPMs in improving TG (90.1%), HDL (86.1%), and CRP (92.6%), respectively. No serious adverse events were reported. Conclusions For CAP patients, CWM + XSBX was among the most effective in reducing carotid maximal plaque area, atherosclerotic plaque Course score, TC and LDL levels, and CWM + JZL was the most effective in reducing IMT. Overall, CWM + XSBX may be considered an effective intervention for the treatment of CAP. This study provides reference and evidence for the clinical optimization of TCPM selection in CAP treatment. More adequately powered, well− designed clinical trials to increase the quality of the available evidence are still needed in the future due to several limitations.

CRISPR/Cas9 is a revolutionary genome editing technology with the tremendous advantages such as precisely targeting/shearing ability, low cost and convenient operation, becoming an efficient and indispensable tool in biological research. As a disruptive technique, CRISPR/Cas9 genome editing has a great potential to realize a future breakthrough in the clinical bone and cartilage repairing as well. This review highlights the research status of CRISPR/Cas9 system in bone and cartilage repair, illustrates its mechanism for promoting osteogenesis and chondrogenesis, and explores the development tendency of CRISPR/Cas9 in bone and cartilage repair to overcome the current limitations.

Two-stage reverse osmosis (RO) processes with intermediate concentrate demineralization (ICD) provide an efficient strategy to treat brines with high CaSO4 contents and reduce concentrate discharge. In this paper, an SRO concentrate is treated using ICD to remove CaSO4 and then mixed with a PRO concentrate for further desalination in SRO, thereby reducing the discharge of the concentrate. We investigate the selection and degradation of scale inhibitors, as well as seeded precipitation in the two-stage RO process with ICD, to achieve a high water recovery rate. A scale inhibitor is added to restrain CaSO4 crystallization on the membrane surface, and the optimized scale inhibitor, RO-400, is found to inhibit calcium sulfate scaling effectively across a wide range of the saturation index of gypsum (SIg) from 2.3 to 6. Under the optimized parameters of 40 W UV light and 70 mg/L H2O2, UV/H2O2 can degrade RO-400 completely in 15 min to destroy the scale inhibitor in the SRO concentrate. After scale inhibitor degradation, the SRO concentrate is desaturated by seeded precipitation, and the reaction degree of CaSO4 reaches 97.12%, leading to a concentrate with a low SIg (1.07) for cyclic desalination. Three UVD-GSP cycle tests show that the reused gypsum seeds can also ensure the effect of the CaSO4 precipitation process. This paper provides a combined UVD-GSP strategy in two-stage RO processes to improve the water recovery rate for CaSO4-contained concentrate.

Rapid advancements in traditional bone tissue engineering have led to innovation in bone repair models and the resolution of insurmountable clinical issues like graft scarcity. The pathophysiological process of treating bone disease, however, is a multidimensional and multimodal regenerative regulatory mechanism that includes numerous immune, inflammatory, or metabolic responses related to the graft or the organism itself. Based on a 3D in vitro cell culture system that is remarkably identical to the body's bone tissue, the bone organoid is a biomimicking bone organ environment. It can accurately mimic the actual repair and regeneration condition in vivo because it shares the same physiological function, structure, morphology, and metabolic process as endogenous bone tissue. As a disruptive regenerative medicine technology, it has wide application prospects in the fields of organ development, gene editing, disease modeling, and precision therapy. Herein, the development process and physiological basis of different cell‐based bone organoids are reviewed, the current status of the application of different materials, cells, and construction methods for building bone organoids is described, and the prospects and challenges for the development of bone organoids in future medical fields is discussed.

Abstract Postmenopausal osteoporosis is one of the most prevalent skeletal disorders in women and is featured by the imbalance between intraosseous vascularization and bone metabolism. In this study, a pH‐responsive shell–core structured micro/nano‐hydrogel microspheres loaded with polyhedral oligomeric silsesquioxane (POSS) using gas microfluidics and ionic cross‐linking technology are developed. This micro/nano‐hydrogel microsphere system (PDAP@Alg/Cs) can achieve oral delivery, intragastric protection, intestinal slow/controlled release, active targeting to bone tissue, and thus negatively affecting intraosseous angiogenesis and osteoclastogenesis. According to biodistribution data, PDAP@Alg/Cs can successfully enhance drug intestinal absorption and bioavailability through intestine adhesion and bone targeting after oral administration. In vitro and in vivo experiments reveal that PDAP@Alg/Cs promoted type H vessel formation and inhibited bone resorption, effectively mitigating bone loss by activating HIF‐1α/VEGF signaling pathway and promoting heme oxygenase‐1 (HO‐1) expression. In conclusion, this novel oral micro/nano‐hydrogel microsphere system can simultaneously accelerate intraosseous vascularization and decrease bone resorption, offering a brand‐new approach to prevent postmenopausal osteoporosis.

For decades, researches have concentrated on the mechanical properties, biodegradation, and biocompatibility of implants used in the therapy of large size bone defect. In vivo studies demonstrate that bioabsorbable bone substitute materials can reduce the risk of common symptoms such as inflammation and osteonecrosis caused by bio-inert materials after long-term implantation. Several organic, inorganic, and composite materials have been approved for clinical application, based on their unique characteristics and advantages. Although some artificial bioabsorbable bone substitute materials have been used for years, there are still some disadvantages existing, such as low mechanical strength, high brittleness, and low degradation rate. Therefore, novel bioabsorbable composite materials biomaterials have been developed for bone defect repair. In this review, we provide an overview of the development of artificial bioabsorbable bone substitute materials and highlight the advantages and disadvantages. Furthermore, recent advances in bioabsorbable bone substitute materials used in bone defect repair are outlined. Finally, we discuss current challenges and further developments in the clinical application of bioabsorbable bone substitute materials.

There are still challenges in applying drug nanocarriers for in situ sustained macrophage targeting and regulation, due to the rapid clearance of nanocarriers and burst drug release in vivo. Herein, a nanomicelle–hydrogel microsphere, characterized by its macrophage-targeted nanosized secondary structure that allows it to accurately bind to M1 macrophages through active endocytosis, is employed for in situ sustained macrophage targeting and regulation, and addresses the insufficient osteoarthritis therapeutic efficacy caused by rapid clearance of drug nanocarriers. The 3-dimensional structure of a microsphere can prevent the rapid escape and clearance of a nanomicelle, thus keeping it in joints, while the ligand-guided secondary structure can carry drugs to accurately target and enter M1 macrophages, and release drugs via the transition from hydrophobicity to hydrophilicity of nanomicelles under inflammatory stimulation inside the macrophages. The experiments show that the nanomicelle–hydrogel microsphere can in situ sustainably target and regulate M1 macrophages for more than 14 days in joints, and attenuate local “cytokine storm” by continuous M1 macrophage apoptosis promotion and polarization inhibition. This micro/nano-hydrogel system shows excellent ability to sustainably target and regulate macrophage, realizes the improvement of drug utilization and efficacy inside the macrophage, and thereby can be a potential platform for treating macrophage-related diseases.

Summary: Ganoderma lucidum is a traditional Chinese medicine with a variety of active compounds and possesses adequate lipid-lowering and anti-atherosclerotic effects. However, its main active components and potential mechanisms still remain unclear. Here, we evaluated the anti-hyperlipidemic effect of the adenosine extract from Ganoderma lucidum (AEGL) in high-fat-diet (HFD)-induced hyperlipidemic ApoE−/− mice and explored the underlying biological mechanism by multi-omics analysis. Treatment with AEGL for 8 weeks significantly decreased the serum levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-c) by 45.59%, 41.22%, and 39.02%, respectively, as well as reduced liver TC and TG by 44.15% and 76.23%, compared with the HFD-only group. We also observed significant amelioration of hepatic steatosis without liver and kidney damage after AEGL treatment. Regulating the expression and acetylation/crotonylation of proteins involved in the PPAR signaling pathway may be one of the potential mechanisms involved in the observed lipid-lowering effects of AEGL.

BackgroundUnlike chemical drugs with a single or a few kinds of active compounds, traditional Chinese medicines (TCMs)uses herbal formulas composed of numerous kinds of chemical constituents. Therefore, TCM clinical trials require unique and stricter standards for collecting, preserving, and transporting fecal samples than those used for chemical drugs. Unfortunately, there are no special standards for processing fecal samples in TCM clinical trials.MethodsWe invited interdisciplinary experts within TCM clinical trials and gut microbiome research to help formulate this standard. After more than a year’s in-depth discussion and amendments, we achieved a standard via expert interviews, literature research, questionnaire surveys, and public opinion solicitation. This standard has been reviewed and approved by the Standards Office of China of the Association of Chinese medicine.ResultsWe established a sample information processing method prior to TCM clinical sample collection, which is adapted to the unique features of TCM. The method formulates detailed processing requirements for TCM information in addition to the factors that may disturb the gut microbiome. We also constructed a set of methods for collecting, preserving, and transporting fecal samples that meet the characteristics of TCM. These methods formulate detailed operating specifications on the collection approaches, storage conditions, transportation requirements, and management of fecal samples.ConclusionsThis standard guides the information processing prior to sample collection and the standard operating procedures for the collection, preservation, and transportation of fecal samples in TCM clinical trials, which also can be used as a reference by clinicians and researchers in modern medicines.

In situ-activated therapy is a decent option for localized diseases with improved efficacies and reduced side effects, which is heavily dependent on the local conversion or activation of bioinert components. In this work, we applied a phospholipid-mimic artemisinin prodrug (ARP) for preparing an injectable nano/microsphere to first realize an in situ-activated therapy of the typical systemically administrated artemisinin-based medicines for a localized rheumatoid arthritis (RA) lesion. ARP is simultaneously an alternative of phospholipids and an enzyme-independent activable prodrug, which can formulate “drug-in-drug” co-delivery liposomes with cargo of partner drugs (e.g., methotrexate). To further stabilize ARP/methotrexate “drug-in-drug” liposomes (MTX/ARPL) for a long-term intra-articular retention, a liposome-embedded hydrogel nano/microsphere (MTX/ARPL@MS) was prepared. After the local injection, the MTX/ARPL could be slowly released because of imine hydrolysis and targeted to RA synovial macrophages and fibroblasts simultaneously. ARP assembly is relatively stable before cellular internalization but disassembled ARP after lysosomal escape and converted into dihydroartemisinin rapidly to realize the effective in situ activation. Taken together, phospholipid-mimic ARP was applied for the firstly localized in situ-activated RA therapy of artemisinin-based drugs, which also provided a brand-new phospholipid-mimic strategy for other systemically administrated prodrugs to realize a remodeling therapeutic schedule for localized diseases.

Novel polymers applied in economic membrane technologies are a perennial hot topic in the fields of natural gas purification and O2 enrichment. Herein, novel hypercrosslinked polymers (HCPs) incorporating 6FDA-based polyimide (PI) MMMs were prepared via a casting method for enhancing transport of different gases (CO2, CH4, O2, and N2). Intact HCPs/PI MMMs could be obtained due to good compatibility between the HCPs and PI. Pure gas permeation experiments showed that compared with pure PI film, the addition of HCPs effectively promotes gas transport, increases gas permeability, and maintains ideal selectivity. The permeabilities of HCPs/PI MMMs toward CO2 and O2 were as high as 105.85 Barrer and 24.03 Barrer, respectively, and the ideal selectivities of CO2/CH4 and O2/N2 were 15.67 and 3.00, respectively. Molecular simulations further verified that adding HCPs was beneficial to gas transport. Thus, HCPs have potential utility in fabrication of MMMs for facilitating gas transport in the fields of natural gas purification and O2 enrichment.

Background: Given the complexity of stroke treatment and the current widespread use of traditional Chinese medicine (TCM) in the absence of robust, large, long-term effectiveness and safety studies, and the lack of nationwide epidemiology and clinical characteristics of patients with stroke receiving TCM treatment, the acquisition of data from longitudinal cohorts is essential. We intend to generate the major clinical characteristics of patients with stroke who receive TCM treatment and to investigate the effectiveness and safety of TCM in the Chinese population.Methods: The China Stroke Registry for Patients with Traditional Chinese Medicine (CASES-TCM) study is a prospective, multicenter, observational disease registry aiming to register 20,000 hospitalized patients. Eligible adult patients with clearly diagnosed acute ischemic stroke or intracerebral hemorrhage within 7 days of symptom onset will be consecutively registered from 126 participating sites across China. Baseline data will be recorded, and all patients will be regularly followed up at 3, 6, 12, and 24 months after stroke onset. Collected data will be entered into a web-based system with high-level data security. The primary outcomes include the distribution of scores on the modified Rankin Scale at the 3-months follow-up, and recurrent stroke events within the 12-months follow-up.Conclusion: To our knowledge, the CASES-TCM study is the first and largest nationwide registry to document comprehensive data on TCM treatment in patients with acute stroke. The findings of this study will be valuable to improve our knowledge about TCM treatment for patients with stroke and its subsequent outcomes in the actual clinical setting, consequently facilitating and standardizing the optimization of individualized interventions with TCM for stroke prevention and treatment in China.Study registration: This study was registered with Clinicaltrials.gov (URL: https://clinicaltrials.gov/, Unique identifier: NCT04921397).

Electronic instrument transformers are expected to play a significant protection and control role in the future smart grids. This paper aims at improving the performance and accuracy of electronic instrument transformers that are replacing the conventional current and potential transformers in the future digital substations. One of the main issues associated with the electronic instrument transformer is its poor thermal stability that affects the accuracy of the measurements. In this paper, to overcome this issue, a new wireless temperature measurement and compensation technique is proposed. In this technique, the operating temperature of the electronic transformer is continuously monitored and its impact on the measurements is compensated in real-time. The experimental results reveal that the proposed technique can effectively improve the thermal stability and measurement accuracy of the electronic instrument transformers.

Background: Although revascularization treatment is recommended as the first-line therapy for patients with non-minor acute ischemic stroke (AIS), it only benefits a minority of patients. Previous studies have reported the positive effects of Panax notoginseng saponins (PNS) (Xueshuantong lyophilized powder) on AIS, however, there have been no rigorous trials. This study aims to assess the efficacy and safety of PNS therapy for patients with AIS.Methods: The Evaluation of Xueshuantong in Patients with acutE ischemiC sTroke (EXPECT) trial is a multicenter, randomized, placebo-controlled, double-blind study aiming to enroll 480 patients in China. Eligible patients with AIS within 72 h of symptom onset will randomly receive either PNS or PNS placebo for 10 days and subsequently be followed up to 90 days. The primary outcome will be a change in the National Institute of Health Stroke Scale (NIHSS) score from baseline to 10 post-randomization days. The secondary outcomes include early neurological improvement (proportion of patients with NIHSS score 0–1), and Patient-Reported Outcomes Scale for Stroke score at 10 post-randomization days, the proportion of patients with life independence (modified Rankin Scale score of 0–1), the proportion of patients with a favorable outcome (Barthel Index ≥90), and Stroke-Specific Quality of Life score at 90 days. Adverse events or clinically significant changes in vital signs and laboratory parameters, regardless of the severity, will be recorded during the trial to assess the safety of PNS.Conclusions: To our knowledge, this study is the first double-blind trial to assess the efficacy and safety of PNS in patients with AIS. Findings of the EXPECT trial will be valuable in improving evidence regarding the clinical application of PNS therapy in patients with AIS ineligible for revascularization treatment in the reperfusion era.

This paper proposes an improved online calibration technique for digital input electricity meters. The technique employs a double-spectral-line interpolation fast Fourier transform algorithm with four-item, three-order Nuttall window to reduce the measurement error caused by spectrum leakage, frequency fluctuation, noise pollution, and harmonic interference. A calibration system of friendly human-computer interaction is designed using LabVIEW. Simulation and practical results show that the proposed calibration system with improved Nuttall window algorithm is of high accuracy and reliability when compared with the traditional calibration algorithm currently used by industry practice.

This study aimed to provide comparative information of pharmaceutical properties, including particle morphology and distribution uniformity, solubility, presence of residual solvent and insoluble particles, and antimicrobial activities, between brand-name meropenem (Mepem®, BNM) and its six generic products (GPs A-F) marketed in China. Particles of GP-A and -C in dry powder had similar diameters of BNM, while other GPs were larger. Only BNM and GP-A were completely dissolved within 100 s in the lab condition. No insoluble particles >25 μm in diameter were detected in BNM and GP-E. Regarding stability of GPs solutions evaluated by concentration of open-ring metabolites at 6 h and 8 h, BNM showed the lowest open-ringed metabolite concentrates. Residual solvent of acetone detected in one GP showed the maximum value, while ethanol and ethyl acetate were detected both in product E and product F. The concordance rates (%) of minimum inhibitory concentration (MIC) of each generic compared to BNM were 89.5, 85, 87.5, 88, 88.5, and 86.5, respectively, although no significant difference was reached in MIC. Pharmaceutical characteristic differences between the BNM and GPs identified in this study could provide insights into understanding the deviations in the drug manufacturing processes of generic drugs.

In the production of acrylic acid, the concentration of acrylic acid solution from the adsorption tower was low, which would lead to significant energy consumption in the distillation process to purify acrylic acid, along with the production of a large amount of wastewater. Reverse osmosis (RO) was proposed to concentrate the acrylic acid aqueous solution taken from a specific tray in the absorption tower. The effects of operating conditions on the permeate flux and acid retention were studied with two commercial RO membranes (SWC5 and SWC6). When the operating pressure was 4 MPa and the temperature was 25 °C, the permeate fluxes of two membranes were about 20 L·m−2·h−1. The acrylic acid and acetic acid retentions were about 80% and 78%, respectively. After being immersed in the acid solutions for several months, the characteristics of the two membranes were tested to evaluate their acid resistance. After six months of exposure to the acid solution containing 2.5% acrylic acid and 2.5% acetic acid, the retentions of acrylic acid and acetic acid were decreased by 5.7% and 4.1% for SWC5 and 4.9% and 2.2% for SWC6, respectively. The changes of membrane surface morphology and chemical composition showed the hydrolysis of some amide bonds.

The Plasmodium falciparum proteasome is a potential antimalarial drug target. We have identified a series of amino-amide boronates that are potent and specific inhibitors of the P. falciparum 20S proteasome (Pf20S) β5 active site and that exhibit fast-acting antimalarial activity. They selectively inhibit the growth of P. falciparum compared with a human cell line and exhibit high potency against field isolates of P. falciparum and Plasmodium vivax. They have a low propensity for development of resistance and possess liver stage and transmission-blocking activity. Exemplar compounds, MPI-5 and MPI-13, show potent activity against P. falciparum infections in a SCID mouse model with an oral dosing regimen that is well tolerated. We show that MPI-5 binds more strongly to Pf20S than to human constitutive 20S (Hs20Sc). Comparison of the cryoelectron microscopy (EM) structures of Pf20S and Hs20Sc in complex with MPI-5 and Pf20S in complex with the clinically used anti-cancer agent, bortezomib, reveal differences in binding modes that help to explain the selectivity. Together, this work provides insights into the 20S proteasome in P. falciparum, underpinning the design of potent and selective antimalarial proteasome inhibitors. [ABSTRACT FROM AUTHOR]

Takayasu arteritis (TA) is now recognized worldwide and is a disease that mainly affects the aorta and its main branches. TA rarely involves the small or medium-sized vessels. Certain vascular lesions, such as arterial stenosis, occlusion, and aneurysm are common with TA. However, patients with new-onset TA who present with left main trunk acute non-ST segment elevation myocardial infarction are extremely rare. We report a 16-year-old female patient with non-ST segment elevation myocardial infarction due to severe stenosis of the left main coronary artery that was caused by TA. She was eventually diagnosed with TA and underwent successful coronary artery stenting combined with glucocorticoids and folate reductase inhibitor therapy. Over the 1-year follow-up, she experienced two episodes of chest pain and was admitted to the hospital. During the second hospitalization, coronary angiography (CAG) revealed 90% stenosis of the original left main trunk (LM) stent. Following percutaneous coronary angiography (PTCA), drug-coated balloon (DCB) angioplasty was performed. Fortunately, a clear diagnosis of TA was made, and treatment was initiated with an interleukin-6 (IL-6) receptor inhibitor. Early diagnosis and therapy for TA are emphasized.

In order to reduce the cost of chemical softening, the seeded precipitation assisted nanofiltration (NF) process was introduced into zero liquid discharge (ZLD) of flue-gas desulfurization (FGD) wastewater treatment. A pilot-scale system was developed and run for 168 h in a coal-fired power plant. The system mainly consists of lime softening, ambient temperature crystallizer (ATC) and NF, in which the raw water treatment capacity was 1 m3/h. The results indicated that the system operated stably, the softening cost was 13.30 RMB/m3, and the electricity cost was 3.39 RMB/m3 for the FGD wastewater in this pilot system. High quality gypsum was got from the ATC unit, of which the purity was 95.8%. Through this system, the hardness removal rate was higher than 98.9% and the water recovery rate reached 96%. In addition, the pressure and permeate flux kept stable in the ultrafiltration (UF) unit and NF unit, indicating no scaling occurred in the two units during 168 h test. Thus, a feasible and cost-effective process was provided by using the seeded precipitation assisted NF to deal with the FGD wastewater. HIGHLIGHTS Seeded precipitation assisted NF is introduced into ZLD process of FGD wastewater.; The softening cost is 13.30 RMB/m3 and much less than softening by Na2CO3.; The hardness removal rate of this pilot system is higher than 98.9%.; High quality gypsum was got from the ATC unit, of which the purity was 95.8%.;

Increasingly strict constraints on the boron concentration for safe drinking and irrigation water present a tremendous challenge for the design of seawater reverse osmosis (RO) desalination systems. This work presents an optimization study of a seawater reverse osmosis RO network with permeate split (PS) design under boron concentration restrictions. Front part permeates with better quality and higher flux are sent directly to the product, and back part permeates are reprocessed in pass 2 with high pH value. The irreversible thermodynamic model is employed to describe the membrane transport behavior of boron. Constraints for the system flow and operation conditions are added to guarantee safe operating of the RO system. Both single-product and two-product RO systems are optimized for different types of feed seawater. Results show that the PS design is mainly dominated by the boron constraints, while the system recovery is mainly controlled by the feed salt concentration. Due to the upper bound of pH for pass 2, PS design could be introduced for pass 2 to improve the boron rejection. For a two-product output system, the permeates from both RO pass 1 and pass 2 could be split and sent to different products. In general, PS design could offer lower water cost, lower energy consumption, and smaller system size compared with normal design. Not only the operation conditions but also the flow structure of the RO system should be adjusted according to both membrane fouling and degradation with time. [ABSTRACT FROM AUTHOR]

An analytical solution for the seismic-induced thrust and moment of the circular tunnel in half-space under obliquely incident P waves is developed in this study, which is the superposition of the solution for deep tunnels under incident and reflected P waves and the reflected SV waves. To consider tangential contact stiffness at the ground-tunnel interface, a spring-type stiffness coefficient is introduced into the force-displacement relationship. Moreover, the tunnel lining is treated as the thick-wall cylinder, providing more precise forecasts than beam or shell models used in previous analytical solution, especially for tunnels with thick lining. The reliability of the proposed analytical solution is assessed by comparing with the dynamic numerical results. Based on the proposed analytical solution, parametrical studies are conducted to investigate the effect of some critical factors on the tunnel’s seismic response, including the incident angles, the tangential contact stiffness at the ground-tunnel interface, and the relative stiffness between the ground and the tunnel. The results demonstrate that the proposed analytical solution performs well and can be adopted to predict the internal forces of circular tunnels under obliquely incident P waves in seismic design.