Role of the screening with coronary computed tomography angiography on lipid management and risk factors control in an asymptomatic Chinese population: a community-based, parallel-group, open-label, randomized clinical trial (RESPECT2).

BACKGROUND: Lipid management based on cardiovascular risk level is the cornerstone of primary prevention of coronary artery disease (CAD), while the accuracy and adherence of traditional cardiovascular risk stratification have been questioned. Prevention strategies based on imaging screening for atherosclerotic plaques are found to be more objective and adherent in recent studies. This trial aims to investigate the role of coronary computed tomography angiography (CCTA) in guiding the primary prevention of CAD in a randomized controlled design. METHODS: Approximately 3400 middle-aged asymptomatic community participants will be recruited and randomized in a 1:1 ratio to a traditional cardiovascular risk score-guided (usual care group) or CCTA-guided (CCTA group) strategy. Participants with cardiovascular disease, prior lipid-lowering therapy, CCTA contraindication, or serious diseases that affect life span will be excluded. The intervention strategy includes blood pressure, blood glucose, and lipid management and lifestyle modifications. Blood pressure and glucose targets and lifestyle modification recommendations keep the same in both strategies, while lipid management is personalized based on traditional risk level or CCTA results, respectively. The primary outcome is the proportion of participants taking lipid-lowering medication regularly at both 6 and 12 months. The secondary outcomes include the proportion of participants achieving low-density lipoprotein cholesterol lowering targets at 12 months, mean changes in lipid levels from baseline to 12 months, barriers to adherence, adverse reactions related to CCTA examination, and cardiovascular events. DISCUSSION: The study is the first randomized clinical trial to examine the effectiveness of a CCTA-guided versus a traditional risk score-guided primary prevention strategy in an asymptomatic community-based population. TRIAL REGISTRATION: ClinicalTrials.gov NCT05725096. Registered on 2 February 2023.

Global progress in clinical research on human respiratory syncytial virus vaccines.

Human respiratory syncytial virus (hRSV) not only affects newborns but also older adults, contributing to a substantial worldwide burden of disease. However, only three approved hRSV vaccines remain commercially available to date. The development of a safe, practical and broad-spectrum vaccine suitable for all age groups remains extremely challenging. Using five different approaches-live-attenuated, recombinant-vector, subunit, particle-based, and mRNA-nearly 30 hRSV vaccine candidates are currently conducting clinical trials worldwide; moreover, > 30 vaccines are under preclinical evaluation. This review presents a comprehensive overview of these hRSV vaccines along with prospects for the development of infectious disease vaccines in the post-COVID-19 pandemic era.

Continuous Synthesis and Processing of Covalent Organic Frameworks in a Flow Reactor.

Covalent organic frameworks (COFs) are typically prepared in the form of insoluble microcrystalline powders using batch solvothermal reactions that are energy-intensive and require long annealing periods (>120 °C, >72 h). Thus, their wide-scale adoption in a variety of potential applications is impeded by complications related to synthesis, upscaling, and processing, which also compromise their commercialization. Here we report a strategy to address both the need for scalable synthesis and processing approaches through the continuous, accelerated synthesis, and processing of imine- and hydrazone-linked COFs using a flow microreactor. The flow microreactor is capable of unprecedented COF productivities, up to 61,111 kg m-3 day-1, and provides control over key stages of COF formation, including nanoparticle growth, self-assembly, and precipitation. Additionally, the technique successfully yields highly crystalline and porous COFs in versatile macroscopic structures such as monoliths, membranes, prints, and packed beds. We also show that a COF synthesized using the flow microreactor acts as an excellent photocatalyst for the photocatalytic degradation of perfluorooctanoic acid (PFOA) outperforming the degradation efficiency of its batch analogue and other classical photocatalysts such as titanium dioxide (TiO2).

NiO/AgNPs nanowell enhanced SERS sensor for efficient detection of micro/nanoplastics in beverages.

The ubiquity of plastic products has led to an increased exposure to micro and nano plastics across diverse environments, presenting a novel class of pollutants with substantial health implications. Emerging research indicates their capacity to infiltrate human organs, posing risks of tissue damage and carcinogenesis. Given the prevalent consumption of beverages as a primary vector for these plastics' entry into the human system, there is an imperative need for the advancement of precise detection methodologies in liquids. In this study, we introduce a substrate comprising a Nickel Oxide (NiO) nanosheet array decorated with Silver Nanoparticles (AgNPs) for the Surface-Enhanced Raman Spectroscopy (SERS) analysis of micro//nano plastics. This configuration, leveraging a unique nanowell architecture alongside silver plasmonic enhancement, demonstrates unparalleled sensitivity and repeatability in signal, facilitating the accurate quantification of these contaminants. Through the application of a portable Raman apparatus, this study successfully identifies prevalent micro/nano plastics including polystyrene (PS), polyethylene (PE), and polypropylene (PP), achieving detection sensitivities of 5 µg/mL, 25 µg/mL, and 25 µg/mL, respectively. Moreover, the substrate's efficacy extends to the detection of PS within commonly consumed beverages such as water, milk, and liquor with sensitivities of 25 µg/mL, 50 µg/mL, and 50 µg/mL, respectively. These findings highlight the substrate's potential as an expedient and effective sensor for the real-time monitoring of micro/nano plastic pollutants.

Tracking chemical feature releases from plastic food packaging to humans.

Humankind are being exposed to a cocktail of chemicals, such as chemicals released from plastic food packaging. It is of great importance to evaluate the prevalence of plastic food packaging-derived chemicals pollution along the flow of food-human. We developed a robust and practical database of 2101 chemical features associated with plastic food packaging that combined data from three sources, 925 of which were acquired from non-target screening of chemical extracts from eight commonly used plastic food packaging materials. In this database, 625 features, especially half of the non-targets, were potential migrants who likely entered our bodies through dietary intake. Biomonitoring analysis of plastic chemical features in foodstuffs or human serum samples showed that approximately 78 % of the 2101 features were detectable and approximately half were non-targets. Of these, 17 plastic chemicals with high detection frequencies (DFs) in the human serum were confirmed to be functional chemical additives. Together, our work indicates that the number of plastic chemicals in our bodies could be far greater than previously recognized, and human exposure to plastic chemicals might pose a potential health risk.

Research on Adaptive Closed-Loop Control of Microelectromechanical System Gyroscopes under Temperature Disturbance.

Microelectromechanical System (MEMS) gyroscopes are inertial sensors used to measure angular velocity. Due to their small size and low power consumption, MEMS devices are widely employed in consumer electronics and the automotive industry. MEMS gyroscopes typically use closed-loop control systems, which often use PID controllers with fixed parameters. These classical PID controllers require a trade-off between overshoot and rise time. However, temperature variations can cause changes in the gyroscope's parameters, which in turn affect the PID controller's performance. To address this issue, this paper proposes an adaptive PID controller that adjusts its parameters in response to temperature-induced changes in the gyroscope's characteristics, based on the error value. A closed-loop control system using the adaptive PID was developed in Simulink and compared with a classical PID controller. The results demonstrate that the adaptive PID controller effectively tracked the changes in the gyroscope's parameters, reducing overshoot by 96% while maintaining a similar rise time. During gyroscope startup, the adaptive PID controller achieves faster stabilization with a 0.036 s settling time, outperforming the 0.06 s of the conventional PID controller.

Research on the Mechanism of Buyang Huanwu Decoction in the Amelioration of Age-Associated Memory Impairment Based on the "Co-occurrence Network Regulation of Intestinal Microecology-Host Metabolism-Immune Function".

ETHNOPHARMACOLOGICAL RELEVANCE: Brain aging can promote neuronal damage, contributing to aging-related diseases like memory dysfunction. Buyang Huanwu Decoction (BYHWD), a traditional Chinese medicine formula known for tonifying qi and activating blood circulation, shows neuroprotective properties. Despite this, the specific mechanism by which BYHWD improves age-associated memory impairment (AAMI) has not been explored in existing literature. AIM OF THE STUDY: This study aimed to investigate the mechanism of BYHWD in the improvement of AAMI based on the "co-occurrence network regulation of intestinal microecology-host metabolism- immune function". MATERIALS AND METHODS: Firstly, D-galactose was performed to induce a rat model of AAMI. Learning and memory deficits was assessed by the Morris water maze test. H&E and Nissl staining were used to observe the pathological changes in neurons in the hippocampus of rats. Meanwhile, the levels of pro-inflammatory cytokines and the activation of antioxidant enzymes in rat serum were measured using ELISA. Finally, an integrated pharmacological approach was applied to explore the potential mechanism of BYHWD in improving AAMI. RESULTS: Our results indicated that BYHWD significantly mitigated the pathological structure of the hippocampus, reversed the levels of IL-6, TNF-α, GSH, and CAT in the serum, and improved learning and memory in aging rats. Transcriptomics combined with network pharmacology showed that energy metabolism and the inflammatory response were the key biological pathways for BYHWD to ameliorate AAMI. Integrative analysis of the microbiome and metabolomics revealed that BYHWD has the potential to restore the balance of abundance between probiotics and harmful bacteria, and ameliorate the reprogramming of energy metabolism caused by aging in the brain. The co-occurrence network analysis demonstrated that a strong correlation between the treatment of AAMI and the stability of intestinal microecology, host metabolism, and immune network. CONCLUSION: The findings of this study collectively support the notion that BYHWD has a superior therapeutic effect in an AAMI rat model. The mechanism involves regulating the "intestinal microecology-metabolism-immune function co-occurrence network" system to restore the composition of gut microbiota and metabolites. This further improves the metabolic phenotype of brain tissue and maintains the homeostasis of central nervous system's immunity, leading to an improvement in AAMI. Consequently, this study offers a unique perspective on the prevention and treatment of AAMI. And, BYHWD is also considered to be a promising preclinical treatment for improving AAMI.

Risk factors and clinical outcomes associated with multiple as opposed to single pathogens detected on the gastrointestinal disease polymerase chain reaction assay.

BACKGROUND: The use of gastrointestinal disease multiplex polymerase chain reaction (GI PCR) testing has become common for suspected gastrointestinal infection. Patients often test positive for multiple pathogens simultaneously through GI PCR, although the clinical significance of this is uncertain. METHODS: This retrospective cohort study investigated risk factors and clinical outcomes associated with detection of multiple (as opposed to single) pathogens on GI PCR. We included adult patients who underwent GI PCR testing from 2020 to 2023 and had one or more pathogens detected. We compared patients with multiple versus those with single pathogens and hypothesized that immunosuppression would be a risk factor for detection of multiple pathogens. We further hypothesized that, during the 90 days after GI PCR testing, patients with multiple pathogens would have worse clinical outcomes such as increased rates of emergency department (ED) visits, death, hospitalization, or ambulatory care visits. RESULTS: GI PCR was positive in 1341 (29%) of tested patients; 356 patients had multiple pathogens and 985 had one pathogen. The most common pathogens included Enteropathogenic Escherichia coli (EPEC, 27%), norovirus (17%), and Enteroaggregative E. coli (EAEC, 14%) in both multi- and singly positive patients. Immunosuppression was not associated with multiple pathogens (adjusted odds ratio [aOR] 1.35, 95% CI 0.96, 1.86). The factors most associated with multiple pathogens were Hispanic ethnicity (OR 1.86, 95% CI 1.42, 2.45) and chronic kidney disease (OR 1.69, 95% CI 1.13, 2.49). Patients with multiple pathogens were more likely to have ED visits during the 90 days after GI PCR testing (40% vs. 32%, p < 0.01), but they were not more likely to die, be hospitalized, or to have ambulatory medical visits. CONCLUSIONS: Immunosuppression was not associated with detection of multiple as opposed to single pathogens on GI PCR testing. There were worse clinical outcomes associated with detection of multiple pathogens, although these effects were modest.

Polyaptamer-Driven Crystallization of Alendronate for Synergistic Osteoporosis Treatment through Osteoclastic Inhibition and Osteogenic Promotion.

Osteoclastic inhibition using antiresorptive bisphosphonates and osteogenic promotion using antisclerostin agents represent two distinct osteoporosis treatments in clinical practice, each individual treatment suffers from unsatisfactory therapeutic efficacy due to its indirect intervention in osteoclasis and promotion of osteogenesis simultaneously. Although this issue is anticipated to be resolved by drug synergism, a tempting carrier-free dual-medication nanoassembly remains elusive. Herein, we prepare such a nanoassembly made of antiresorptive alendronate (ALN) crystal and antisclerostin polyaptamer (Apt) via a nucleic acid-driven crystallization method. This nanoparticle can protect Apt from rapid nuclease degradation, avoid the high cytotoxicity of free ALN, and effectively concentrate in the cancellous bone by virtue of the bone-binding ability of DNA and ALN. More importantly, the acid microenvironment of cancellous bone triggers the disassociation of nanoparticles for sustained drug release, from which ALN inhibits the osteoclast-mediated bone resorption while Apt promotes osteogenic differentiation. Our work represents a pioneering demonstration of nucleic acid-driven crystallization of a bisphosphonate into a tempting carrier-free dual-medication nanoassembly. This inaugural advancement augments the antiosteoporosis efficacy through direct inhibition of osteoclasis and promotion of osteogenesis simultaneously and establishes a paradigm for profound understanding of the underlying synergistic antiosteoporosis mechanism of antiresorptive and antisclerostin components. It is envisioned that this study provides a highly generalizable strategy applicable to the tailoring of a diverse array of DNA-inorganic nanocomposites for targeted regulation of intricate pathological niches.

Study on the structure parameters and design method optimization of blade-type screw steel pipe pile.

The rationality of structure parameters of the blade-type screw steel pipe pile is the major factor in determining the safety, applicability, and economy of a pile foundation, but the existing design methods have not defined the specific approaches to calculating structure parameters of blades and steel pipes. To address this issue, an analysis of the strength theory was performed on spatial helical blades, revealing the ratio of blade width to steel pipe radius as the core index to do the structure parameters design of blade-type screw steel pipe pile and established a mathematical calculation model between the vertical bearing capacity of single pile and a. The rational value of a is 2.0-3.0 using numerical calculation. The correlation between blade thickness and wall thickness of steel pipes was determined using the force analysis based on the synergy between blades and steel pipes. Then the structure parameters design method of blade-type screw steel pipe pile with coordinated parameters was proposed. The rationality and superiority of this design method were verified by comparing the existing test data and the finite element simulative analysis. Based on this design method and the current specifications, such as the Technical Code for Building Pile Foundations, a safe, applicable, and economical optimization design method and flow of blade-type screw steel pipe piles were further proposed for engineering design reference.

In Situ Colorimetric LAMP Based on One-Step Modified Filter Paper to Screen Human Papillomavirus (HPV)16/18 from Clinical Samples.

Cervical cancer is among the most common malignant tumors in women. The development of rapid screening techniques plays an important role in early screening for cancer treatment. We have developed an HPV screening method, which effectively combines the high-efficiency nucleic acid enrichment of chitosan-modified filter paper and the rapid visual detectability of colorimetric LAMP, along with the enhancement of the tolerance ability of the pH-sensitive LAMP reagent to acidic original samples, making the detection of HPV 16/18 easy to carry out and reliable, which is helpful for the epidemiological prevention and control strategies of HPV-induced cancer. This technique can simultaneously exhibit the "in situ amplification" capability of chitosan-modified filter paper and the nontemperature cycle dependence of visual LAMP detection. Therefore, DNA extraction and amplification can be performed efficiently and quickly within a single reaction where all DNA is concentrated in the QF paper disc. By embedding amino-modified filter paper into the plastic chip, a simple and reliable disposable chip was prepared for rapid HPV16 and HPV18 detection from clinical endometrial samples, and the results were 100% consistent with clinical diagnosis. More importantly, even after the sample was diluted 100-fold, HPV16/18-infected cells could be accurately identified, showing the advantages of the system in early cancer screening. Moreover, for endometrial samples containing plenty of cells, the filter paper could be used to enrich cells by filtration, preventing the acidic fluid from impacting pH-induced colorimetric LAMP detection and realizing direct amplification for HPV identification without nucleic acid extraction. This easy-to-operate system that can analyze a wide range of samples will be suitable for routine on-site HPV screening, dramatically extending the applications and utility for rapid, near-patient nucleic acid testing.

[Advances in synthesis of succinic acid using yeast cell factories].

Succinic acid is an important C4 platform compound that serves as a raw material for the production of 1,4-butanediol, tetrahydrofuran, and biodegradable plastics such as polybutylene succinate (PBS). Compared to the traditional petrochemical-based route that uses maleic anhydride as a raw material, the microbial fermentation method for producing succinic acid offers more sustainable economic value and environmental friendliness. Yeasts with good acid tolerance can achieve low-pH fermentation of succinic acid, significantly reducing the cost of product extraction. Therefore, constructing high-yield succinic acid yeast strains through metabolic engineering has garnered increasing attention. This paper systematically introduced the application value and market size of succinic acid, summarized the pathways and key enzymes involved in succinic acid synthesis in microorganisms, and elaborated on the latest research progress in the synthesis of succinic acid using yeast cell factories. It also presented the current status of succinic acid synthesis using non-food raw materials such as glycerol, acetic acid, lignocellulosic hydrolysate, and others as substrates by engineered yeast strains. Finally, the paper provided a prospect for low-pH succinic acid biomanufacturing based on yeast cell factories.

Latent Profile Analysis of Self-Stigma Among Individuals With Schizophrenia and Its Relationship With Illness Perception.

PURPOSE: To investigate self-stigma among individuals with schizophrenia, identify potential categories of self-stigma, and analyze the association between self-stigma categories and dimensions of disease perception. METHOD: Convenience sampling was used to select individuals with schizophrenia (N = 216) in psychiatric hospitals. A General Demographic Information Questionnaire, the Internalized Stigma of Mental Illness Inventory, and Brief Illness Perception Questionnaire were used for data collection. A latent profile analysis was performed on self-stigma characteristics of participants, and potential categories of influencing factors and their relationship with illness perception were examined. RESULTS: Participants were classified into three potential categories: low self-stigma-low resistance (19.4%), medium self-stigma (55.6%), and high self-stigma-high discrimination (25%). Compared with the low self-stigma-low resistance group, those with higher illness representation and illness understanding scores were more likely to be classified as medium self-stigma, and emotional representation was the strongest predictor for high self-stigma-high discrimination. CONCLUSION: Self-stigma among participants was mostly medium to high. Self-stigma of individuals with schizophrenia demonstrates group heterogeneity; therefore, nurses should formulate targeted interventions based on the characteristics of each category to achieve precise interventions and reduce self-stigma. [Journal of Psychosocial Nursing and Mental Health Services, xx(xx), xx-xx.].

The Effects of Climate Change on the Distribution Pattern of Species Richness of Endemic Wetland Plants in the Qinghai-Tibet Plateau.

Wetland ecosystems in the Qinghai-Tibet Plateau (QTP), the region with the richest biodiversity and the most important ecological barrier function at high altitudes, are highly sensitive to global change, and wetland plants, which are important indicators of wetland ecosystem structure and function, are also threatened by wetland degradation. Therefore, a comprehensive study of changes in the geographical distribution pattern of plant diversity, as well as species loss and turnover of wetlands in the QTP in the context of global climate change is of great importance for the conservation and restoration of wetland ecosystems in the QTP. In this study, species turnover and loss of 395 endemic wetland plants of the QTP were predicted based on the SSP2-4.5 climate change scenarios. The results showed that there were interspecific differences in the effects of climate change on the potential distribution of species, and that most endemic wetland plants would experience range contraction. Under the climate change scenarios, the loss of suitable wetland plant habitat is expected to occur mainly in parts of the southern, north-central and north-western parts of the plateau, while the gain is mainly concentrated in parts of the western Sichuan Plateau, the Qilian Mountains, the Three Rivers Source Region and the northern Tibetan Plateau. Overlaying the analysis of priority protected areas with the established protected areas in the QTP has resulted in the following conservation gaps: the eastern Himalayan region, midstream of the Yarlung Zangbo River, the transition zone between the northern Tibetan Plateau and the Hengduan Mountains, Minshan-Qionglai mountain, Anyemaqen Mountains (southeast) to Bayankala (southeast) mountains, the southern foothills of the Qilian Mountains and the northern Tibetan Plateau region. In the future, the study of wetland plant diversity in the QTP and the optimisation of protected areas should focus on the conservation gaps. This study is of great importance for the study and conservation of wetland plant diversity in the QTP, and also provides a scientific basis for predicting the response of wetland plants to climate change in the QTP.

A novel bispecific antibody targeting two overlapping epitopes in RBD improves neutralizing potency and breadth against SARS-CoV-2.

SARS-CoV-2 has been evolving into a large number of variants, including the highly pathogenic Delta variant, and the currently prevalent Omicron subvariants with extensive evasion capability, which raises an urgent need to develop new broad-spectrum neutralizing antibodies. Herein, we engineer two IgG-(scFv)2 form bispecific antibodies with overlapping epitopes (bsAb1) or non-overlapping epitopes (bsAb2). Both bsAbs are significantly superior to the parental monoclonal antibodies in terms of their antigen-binding and virus-neutralizing activities against all tested circulating SARS-CoV-2 variants including currently dominant JN.1. The bsAb1 can efficiently neutralize all variants insensitive to parental monoclonal antibodies or the cocktail with IC50 lower than 20 ng/mL, even slightly better than bsAb2. Furthermore, the cryo-EM structures of bsAb1 in complex with the Omicron spike protein revealed that bsAb1 with overlapping epitopes effectively locked the S protein, which accounts for its conserved neutralization against Omicron variants. The bispecific antibody strategy engineered from overlapping epitopes provides a novel solution for dealing with viral immune evasion.

Dual auxotrophy coupled red labeling strategy for efficient genome editing in Saccharomyces cerevisiae.

The homologous recombination strategy has a long history of editing Saccharomyces cerevisiae target genes. The application of CRISPR/Cas9 strategy to editing target genes in S. cerevisiae has also received a lot of attention in recent years. All findings seem to indicate that editing relevant target genes in S. cerevisiae is an extremely easy event. In this study, we systematically analyzed the advantages and disadvantages of homologous recombination (HR) strategy, CRISPR/Cas9 strategy, and CRISPR/Cas9 combined homology-mediated repair (CRISPR/Case9-HDR) strategy in knocking out BY4742 ade2. Our data showed that when the ade2 was knocked out by HR strategy, a large number of clones appeared to be off-target, and 10 %-80 % of the so-called knockout clones obtained were heteroclones. When the CRISPR/Cas9 strategy was applied, 60% of clones were off-target and the rest were all heteroclones. Interestingly, most of the cells were edited successfully, but at least 60 % of the clones were heteroclones, when the CRISPR/Cas9-HDR strategy was employed. Our results clearly showed that the emergence of heteroclone seems inevitable regardless of the strategies used for editing BY4742 ade2. Given the characteristics of BY4742 defective in ade2 showing red on the YPD plate, we attempted to build an efficient yeast gene editing strategy, in which the CRISPR/Cas9 combines homology-mediated repair template carrying an ade2 expression cassette, BY4742(ade2Δ0) as the start strain. We used this strategy to successfully achieve 100 % knockout efficiency of trp1, indicating that technical challenges of how to easily screen out pure knockout clones without color phenotype have been solved. Our data showed in this study not only establishes an efficient yeast gene knockout strategy with dual auxotrophy coupled red labeling but also provides new ideas and references for the knockout of target genes in the monokaryotic mycelium of macrofungi.

Clonorchis sinensis aggravated liver fibrosis by activating PARP-1 signaling to induce parthanatos via DNA damage.

Clonorchis sinensis is an important food-borne zoonotic parasite that is highly associated with liver fibrosis and cholangiocarcinoma. Further understanding of the pathogenesis of C. sinensis, especially liver fibrosis, could help us develop novel strategies for controlling clonorchiasis. Poly (ADP-ribose) polymerase-1 (PARP-1) can induce cellular parthanatos which is reported to be involved in liver fibrosis. Currently, whether C. sinensis could activate PARP-1 signaling to induce parthanatos or whether parthanatos play a role in C. sinensis-induced liver fibrosis is not clear. In the present study, the expression of PARP-1 and parthanatos indicators were detected in C. sinensis-infected mouse liver and in human intrahepatic biliary epithelial cells (HiBEpiCs) incubated with excretory/secretory products (ESPs) of C. sinensis. To explore the role of PARP-1 in C. sinensis infection, PARP-1 inhibitor NMS-P118 was used to block PARP-1 expression in vivo and vitro. The mortality rate, body weight, worm load, liver and bile duct lesions as well as PARP-1 and parthanatos indicators in C57BL/6 mice infected with C. sinensis, or in HiBEpiCs incubated with C. sinensis ESPs and NMS-P118 were analyzed and compared to the group without NMS-P118. The results showed that C. sinensis infection induced the activation of PARP-1 signaling as well as the translocation of AIF and MIF into the nucleus in mouse liver. ESPs of C. sinensis could induce PARP-1 up-regulation, ATP depletion and DNA damage in HiBEpiCs, indicating that C. sinensis could induce parthanatos. Inhibiting PARP-1 with NMS-P118 significantly reduced liver fibrosis and the number of larvae, increased the survival rate and body weight gain of the mice infected with C. sinensis. In addition, NMS-P118 decreased the expression of PARP-1 and alleviated ATP depletion as well as DNA damage in HiBEpiCs incubated with ESPs of C. sinensis. Our data indicated that C. sinensis and its ESPs could activate PARP-1 signaling to induce cellular parthanatos. NMS-P118 treatment alleviated liver fibrosis and promoted survival of the mice by inhibiting PARP-1, which suggested that PARP-1 could be used as a potential therapeutic target against clonorchiasis.

A novel nomogram to predict the recurrence of hepatocellular carcinoma after liver transplantation using extended selection criteria.

BACKGROUND: Liver transplantations (LTs) with extended criteria have produced surgical results comparable to those obtained with traditional standards. However, it is not sufficient to predict hepatocellular carcinoma (HCC) recurrence after LT according to morphological criteria alone. The present study aimed to construct a nomogram for predicting HCC recurrence after LT using extended selection criteria. METHODS: Retrospective data on patients with HCC, including pathology, serological markers and follow-up data, were collected from January 2015 to April 2020 at Huashan Hospital, Fudan University, Shanghai, China. Logistic least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analyses were performed to identify and construct the prognostic nomogram. Receiver operating characteristic (ROC) curves, Kaplan-Meier curves, decision curve analyses (DCAs), calibration diagrams, net reclassification indices (NRIs) and integrated discrimination improvement (IDI) values were used to assess the prognostic capacity of the nomogram. RESULTS: A total of 301 patients with HCC who underwent LT were enrolled in the study. The nomogram was constructed, and the ROC curve showed good performance in predicting survival in both the development set (2/3) and the validation set (1/3) (the area under the curve reached 0.748 and 0.716, respectively). According to the median value of the risk score, the patients were categorized into the high- and low-risk groups, which had significantly different recurrence-free survival (RFS) rates (P < 0.01). Compared with the Milan criteria and University of California San Francisco (UCSF) criteria, DCA revealed that the new nomogram model had the best net benefit in predicting 1-, 3- and 5-year RFS. The nomogram performed well for calibration, NRI and IDI improvement. CONCLUSIONS: The nomogram, based on the Milan criteria and serological markers, showed good accuracy in predicting the recurrence of HCC after LT using extended selection criteria.

Surface electromyography analysis of ankle flexor and extensor activity under different standing stability levels.

Background: To observe the activation strategies of the ankle muscles using surface electromyography (sEMG) during single-leg standing (SLS) and both-leg standing (BLS) on flat ground (FG), soft mat (SM), and BOSU ball (BB) surfaces. Methods: Thirty healthy young adults participated in the study. The muscle activities of the tibialis anterior (TA) and gastrocnemius medial (GM) were measured on the three surfaces during SLS and BLS. Electromyographic evaluations of the TA and GM were recorded during maximum voluntary isometric contractions (MVIC). Muscle activation was evaluated using MVIC%, and muscle co-contraction was evaluated using the co-contraction index (CI). Results: A statistically significant increase was observed in the MVIC% of the TA, GM, and CI on the three surfaces during SLS compared to BLS, except for the comparison of CI on BB between SLS and BLS (t = -1.35, p = 0.19). The MVIC% of the TA and GM during SLS and BLS on BB was significantly increased in comparison with FG and SM. The CI during BLS on BB increased compared to FG (t = 3.19, p < 0.01) and SM (t = 4.64, p < 0.01). The CI during BLS on SM (t = -1.46, p = 0.15) decreased when compared to FG but without statistical significance. Conclusions: SLS and unstable surfaces can induce greater muscle activation, and SLS can have a greater influence on ankle muscles.