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Serum response factor (SRF) controls gene transcription in vascular smooth muscle cells (VSMCs) and regulates VSMC phenotypic switch from a contractile to a synthetic state, which plays a key role in the pathogenesis of cardiovascular diseases (CVD). It is not known how post-translational SUMOylation regulates the SRF activity in CVD. Here we show that Senp1 deficiency in VSMCs increased SUMOylated SRF and the SRF-ELK complex, leading to augmented vascular remodeling and neointimal formation in mice. Mechanistically, SENP1 deficiency in VSMCs increases SRF SUMOylation at lysine 143, reducing SRF lysosomal localization concomitant with increased nuclear accumulation and switching a contractile phenotype-responsive SRF-myocardin complex to a synthetic phenotype-responsive SRF-ELK1 complex. SUMOylated SRF and phospho-ELK1 are increased in VSMCs from coronary arteries of CVD patients. Importantly, ELK inhibitor AZD6244 prevents the shift from SRF-myocardin to SRF-ELK complex, attenuating VSMC synthetic phenotypes and neointimal formation in Senp1-deficient mice. Therefore, targeting the SRF complex may have a therapeutic potential for the treatment of CVD. How post-translational SUMOylation regulates the SRF activity in cardiovascular disease is unclear. Here, the authors report that SRF SUMOylation increased by SENP1 deficiency switches vascular smooth muscle cells from a healthy contractile phenotype to a disease-associated synthetic phenotype. [ABSTRACT FROM AUTHOR]

Despite sufficient studies performed in non-primate animal models, there exists scanty information obtained from pilot trials in non-human primate animal models, severely hindering nanomaterials moving from basic research into clinical practice. We herein present a pioneering demonstration of nanomaterials based optical imaging-guided surgical operation by using macaques as a typical kind of non-human primate-animal models. Typically, taking advantages of strong and stable fluorescence of the small-sized (diameter: ~ 5 nm) silicon-based nanoparticles (SiNPs), lymphatic drainage patterns can be vividly visualized in a real-time manner, and lymph nodes (LN) are able to be sensitively detected and precisely excised from small animal models (e.g., rats and rabbits) to non-human primate animal models (e.g., cynomolgus macaque (Macaca fascicularis) and rhesus macaque (Macaca mulatta)). Compared to clinically used invisible near-infrared (NIR) lymphatic tracers (i.e., indocyanine green (ICG); etc.), we fully indicate that the SiNPs feature unique advantages for naked-eye visible fluorescence-guided surgical operation in long-term manners. Thorough toxicological analysis in macaque models further provides confirming evidence of favorable biocompatibility of the SiNPs probes. We expect that our findings would facilitate the translation of nanomaterials from the laboratory to the clinic, especially in the field of cancer treatment. [ABSTRACT FROM AUTHOR]

Postoperative acute kidney injury (AKI) is a common complication that is associated with chronic kidney disease, early postsurgical mortality, and prolonged hospital stays. Preterm neonates who undergo surgery are at risk factors for AKI due to underdeveloped kidneys. To date, little is known about the incidence and perioperative risk factors for AKI in preterm neonates undergoing noncardiac surgery. Preterm neonates who underwent noncardiac surgery between January May 1, 2020, and February 28, 2023, were enrolled in the trial according to the inclusion criteria. Both multivariable and logistic regression analyses were used to analyze the associations between characteristic data and AKI. In total, 106 preterm neonates met the inclusion criteria, and 25 preterm neonates (23.6%) developed postoperative AKI. Multivariate analysis revealed that the factors associated with AKI were gestational age < 32 weeks [OR: 4.88; 95% CI (1.23–19.42)], preoperative sepsis [OR: 3.98; 95% CI (1.29–12.28)], and intraoperative hypotension [OR: 3.75; 95% CI (1.26–11.15)]. Preterm neonates who developed AKI were more likely to have longer hospital length of stays (38 [18,69] days vs. 21[12,46]) and higher medical costs (93,181.6 [620450.0,173,219.0] ￥ vs. 58,134.6 [31015.1,97,224,1) ￥ than neonates who did not develop AKI. Preterm neonates who underwent noncardiac surgery had a high incidence of AKI. Independent risk factors for AKI in preterm neonates who underwent noncardiac surgery were low gestational age, preoperative sepsis, and intraoperative hypotension. Preterm neonates who developed AKI were more likely to have longer hospital stays and higher medical costs. [ABSTRACT FROM AUTHOR]

Host defense peptide (HDP)-mimicking polymers are promising therapeutic alternatives to antibiotics and have large-scale untapped potential. Artificial intelligence (AI) exhibits promising performance on large-scale chemical-content design, however, existing AI methods face difficulties on scarcity data in each family of HDP-mimicking polymers (<102), much smaller than public polymer datasets (>105), and multi-constraints on properties and structures when exploring high-dimensional polymer space. Herein, we develop a universal AI-guided few-shot inverse design framework by designing multi-modal representations to enrich polymer information for predictions and creating a graph grammar distillation for chemical space restriction to improve the efficiency of multi-constrained polymer generation with reinforcement learning. Exampled with HDP-mimicking β-amino acid polymers, we successfully simulate predictions of over 105 polymers and identify 83 optimal polymers. Furthermore, we synthesize an optimal polymer DM0.8iPen0.2 and find that this polymer exhibits broad-spectrum and potent antibacterial activity against multiple clinically isolated antibiotic-resistant pathogens, validating the effectiveness of AI-guided design strategy. Host defense peptide (HDP)-mimicking polymers are promising therapeutic alternatives. Here, the authors develop an AI-guided framework, and synthesize a polymer DM0.8iPen0.2, which exhibits broad-spectrum and potent antibacterial activity. [ABSTRACT FROM AUTHOR]

The MgO-CaO-B2O3-SiO2 (MCBS) glass–ceramics with different MgO/CaO ratio were designed and prepared. The phase transition, microstructure, dielectric properties and flexural strength of the MCBS system were investigated. The quantitative calculations results showed that the MgO/CaO ratio favored the formation of CaMgSi2O6 phase but hindered the formation of CaSiO3 and CaB2O4 phases. With increasing MgO/CaO ratio, the microstructure of sample changes from dendritic to polygonal shape. The MgO/CaO ratio also affected the properties of matrix. In this study, the 5MgO-36CaO-18B2O3-41SiO2 (mol%) sample sintered at 825 °C for 15 min exhibited superior performance: the density of 2.64 g cm−3, a moderate dielectric constant of 5.92, the dielectric loss of 1.54 × 10–3 (10 GHz), the thermal expansion coefficient of 9.61 ppm K−1, the thermal conductivity of 3.02 W m−1 K−1, and a high flexural strength of 208.7 MPa, which might be a potential material for LTCC applications. [ABSTRACT FROM AUTHOR]

5-Fluorouracil (5-Fu) is a basic drug that is used to treat colorectal cancer. Patients who receive 5-Fu chemotherapy often experience side effects that affect the digestive system, such as intestinal injury and diarrhoea, which significantly affect patient compliance with anticancer treatment and quality of life. Therefore, identifying approaches to treat or prevent these side effects is urgent. Dasabuvir (DSV) is a hepatitis C virus inhibitor, but its impact on 5-Fu-induced intestinal injury remains unknown. Our study investigated the effects of DSV on 5-Fu-induced intestinal injury in HUVECs, HIECs and male BALB/c mice. We found that 5-Fu caused intestinal damage by inducing senescence, increasing inflammatory factor expression, and generating oxidative stress. Compared with 5-Fu treatment alone, DSV inhibited senescence by reducing senescence-β-galactosidase (SA-β-gal) activity, the senescence-associated secretory phenotype (SASP, including IL-1, IL-6, and TNF-α) and senescence marker expression levels (p16, p21, and p53). Moreover, the anti-senescence effect of DSV was achieved by inhibiting the mTOR signaling pathway. DSV increased antioxidant enzyme levels and alleviated intestinal tissue injury in mice. In addition, DSV suppressed the 5-Fu-induced increase the diarrhoea scores and ameliorated the weight loss, food intake and water intake of the mice. Overall, this study indicated that DSV could be used to treat chemotherapy-induced intestinal damage. [ABSTRACT FROM AUTHOR]

Aims: Global warming due to increasing greenhouse gas emissions intensifies frequency and duration of extreme high temperature which has become a primary threat to cool-season crops worldwide. Aim of this study was to examine root adaptability to high temperature regulated by γ-aminobutyric acid (GABA) associated with changes in antioxidant metabolism, root vitality, osmotic balance, and global metabolites remodeling in roots. Methods: A cool-season creeping bentgrass (Agrostis stolonifera) plants were pretreated with or without the 0.5 mM GABA before being subjected to heat stress (35/30 °C) or optimal temperature condition (23/19 °C) for 15 days. Roots were sampled to analyze changes in physiological parameters and metabolomics. Results: Heat stress significantly induced reactive oxygen species production in roots resulting in oxidative damage to proteins and cell membranes. However, the GABA could effectively alleviate heat-induced decline in total antioxidant capacity and also improve multiple antioxidant enzyme activities, root vitality, and osmotic adjustment ability in roots. Metabolomic analysis found that a total of 71 metabolites were jointly or differentially regulated by heat stress or heat stress together with the GABA application in roots. In response to heat stress, the GABA improved the accumulation of multiple amino acids, sugars, organic acids, and other metabolites (urea, putrescine, myoinositol, arbutin, campesterol, and stigmasterol) in roots. Conclusions: GABA could effectively increase antioxidant capacity, root vitality, and osmotic adjustment associated with improved root adaptability to heat stress. In addition, the GABA-regulated metabolites remodeling could be attributed to better energy metabolism, osmotic balance, antioxidant capacity, and cellular structures in roots under heat stress. [ABSTRACT FROM AUTHOR]

For a positive definite Lagrangian, the minimal measure was defined in terms of first homology or cohomology class. For a configuration manifold that has a larger fundamental group than its first homology group, it makes a difference to define minimal measure in terms of path in fundamental group. Unlike Mather measures that are supported only on the level set not below the Mañé critical value in autonomous case, it is found in this paper that newly defined minimal measures are supported on the level sets not only above but also below the Mañé critical value. In particular, the support of the measure for a commutator looks like a figure of four petals that persists when the energy crosses the critical value. [ABSTRACT FROM AUTHOR]

Main conclusion: γ-Aminobutyric acid alleviates acid-aluminum toxicity to roots associated with enhanced antioxidant metabolism as well as accumulation and transportation of citric and malic acids. Aluminum (Al) toxicity has become the main limiting factor for crop growth and development in acidic soils and is further being aggravated worldwide due to continuous industrial pollution. The current study was designed to examine effects of GABA priming on alleviating acid-Al toxicity in terms of root growth, antioxidant defense, citrate and malate metabolisms, and extensive metabolites remodeling in roots under acidic conditions. Thirty-seven-day-old creeping bentgrass (Agrostis stolonifera) plants were used as test materials. Roots priming with or without 0.5 mM GABA for 3 days were cultivated in standard nutrient solution for 15 days as control or subjected to nutrient solution containing 5 mM AlCl3·6H2O for 15 days as acid-Al stress treatment. Roots were sampled for determinations of root characteristics, physiological and biochemical parameters, and metabolomics. GABA priming significantly alleviated acid-Al-induced root growth inhibition and oxidative damage, despite it promoted the accumulation of Al in roots. Analysis of metabolomics showed that GABA priming significantly increased accumulations of organic acids, amino acids, carbohydrates, and other metabolites in roots under acid-Al stress. In addition, GABA priming also significantly up-regulated key genes related to accumulation and transportation of malic and citric acids in roots under acid-Al stress. GABA-regulated metabolites participated in tricarboxylic acid cycle, GABA shunt, antioxidant defense system, and lipid metabolism, which played positive roles in reactive oxygen species scavenging, energy conversion, osmotic adjustment, and Al ion chelation in roots. [ABSTRACT FROM AUTHOR]

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Most current methods for image denoising exploit the global low-rankness and local smoothness priors of images to model them, including independent coding methods and fusion coding methods. However, the former methods require tedious tuning of more than two parameters, while the latter methods treat each singular value of the gradient matrices/tensors equally, thus limiting the flexibility to handle realistic issues. In this paper, we propose the reweighted tensor correlated total variation (RTCTV) norm to further explore and fully exploit the intrinsic structural properties of gradient tensors. The proposed RTCTV regularizer does not require trade-off parameters to balance the two priors, and further effectively utilizes the prior distribution information of the singular values of the gradient tensors. Moreover, for better completing the image denoising task, we consider the importance of gradient tensors in different directions and design a broader denoising model based on RTCTV. We then design an alternating direction method of multipliers-based algorithm to solve the proposed model. Extensive experimental results on multiple types of visual tensor data demonstrate that the proposed method outperforms the compared image denoising methods in both evaluation metrics and visual effects. [ABSTRACT FROM AUTHOR]

Applying a low surface energy water-repellent finish agents to fabric is one of the effective ways to make it obtain water-repellent function. Water-repellent finish agents are mainly divided into two categories, fluorinated and non-fluorinated, and fluorinated water-repellent agents will be gradually banned because of environmental protection issues. Organosilicons, polyacrylates, and dendritic macromolecules are the most studied types of non-fluorinated water-repellent agents, but there are some problems in the preparation and use of these non-fluorinated water-repellent agents. Here, using 58 # fully refined paraffin wax as raw material, the paraffin wax was modified by no catalytic oxidation modification method to improve its emulsification performance. The oxidation-modified paraffin wax was used as raw material to prepare a stable, uniform and good fluidity water-repellent emulsion. The oxidation-modified paraffin wax emulsion was used as a water-repellent agent, and waterborne polyurethane (WPU) was used as a crosslinking agent to finish pure cotton fabrics and polyester/cotton-blended fabrics. After water-repellent finish, the contact angle of pure cotton fabric was 135° and that of polyester/cotton-blended fabric was 145°. This study provides a useful way for exploring non-fluorinated water-repellent agent with low cost and simple production process. [ABSTRACT FROM AUTHOR]

The impact of digital industrialization on regional pollution control and carbon reduction in China is an area that remains largely unexplored despite being a new driving force in promoting high-quality economic development. This study constructs a combined system synergy model to measure the synergistic governance effect of regional pollution and carbon reduction in China from 2011 to 2020 and then estimates the direct impact and spatial spillover effect using a spatial dual-weight model. Our findings indicate that digital industrialization has a greater impact on regional pollution reduction and carbon reduction as geographical distance decreases, with the spillover effect with close geographical relationships being higher than that of adjacent. Furthermore, the heterogeneity analysis reveals that the added value of digital technology and services has a significantly positive effect, while the spatial spillover effect of the added value of digital infrastructure is significantly negative. Finally, our mechanism judgements prove digital industrialization can impact the level of regional co-governance of pollution and carbon reduction through source prevention, process control, and end-treatment. Our study provides a factual basis for further promoting China's environmental pollution control and carbon reduction behavior and offers a method to use different spatial weights in depth. [ABSTRACT FROM AUTHOR]

Association of circulating glycoprotein acetyls (GlycA), a systemic inflammation biomarker, with lung function and respiratory diseases remain to be investigated. We examined the genetic correlation, shared genetics, and potential causality of GlycA (N = 115,078) with lung function and respiratory diseases (N = 497,000). GlycA showed significant genetic correlation with FEV1 (rg = −0.14), FVC (rg = −0.18), asthma (rg = 0.21) and COPD (rg = 0.31). We consistently identified ten shared loci (including chr3p21.31 and chr8p23.1) at both SNP and gene level revealing potential shared biological mechanisms involving ubiquitination, immune response, Wnt/β-catenin signaling, cell growth and differentiation in tissues or cells including blood, epithelium, fibroblast, fetal thymus, and fetal intestine. Genetically elevated GlycA was significantly correlated with lung function and asthma susceptibility (354.13 ml decrement of FEV1, 442.28 ml decrement of FVC, and 144% increased risk of asthma per SD increment of GlycA) from MR analyses. Our findings provide insights into biological mechanisms of GlycA in relating to lung function, asthma, and COPD. Here, the authors observed significant genetic correlation of GlycA with lung function, asthma and COPD and identified ten shared loci revealing potential shared biological mechanisms involving ubiquitination and Wnt/β-catenin signaling. [ABSTRACT FROM AUTHOR]

Use of real-world data (RWD) is gaining wide attention. To bridge the gap between diverse healthcare stakeholders and to leverage the impact of Chinese real-world evidence (RWE) globally, a multi-stakeholder External Advisory Committee (EAC) and EAC meetings were initiated, aiming to elucidate the current and evolving RWD landscape in China, articulate the values of RWE in ensuring Chinese patients' equitable access to affordable medicines and solutions, and identify strategic opportunities and partnerships for expansion of RWE generation in China. Chinese and international experts who are clinicians and academic researchers were selected as EAC members based on their professional background and familiarity with RWD/RWE. Three EAC meetings were held quarterly in 2023. Various topics were presented and discussed for insights and suggestions. Nine experts from China, one from South Korea, and two from Europe were selected as EAC members and attended these meetings. Experts' presentations were summarized by theme, including the RWD landscape and RWE enablement in China, as well as global development of a patient-centric ecosystem. Experts' insights and suggestions on maximizing the RWD/RWE value to accelerate healthcare transformation in China were collected. We concluded that though data access, sharing, and quality are still challenging, RWD is developing to support evidence generation in the medicinal product lifecycle, inform clinical practice, and empower patient management in China. RWD/RWE creates value, accelerates healthcare transformation, and improves patient outcomes. Fostering a patient-centric ecosystem across healthcare stakeholders and maintaining global partnerships and collaboration are essential for unlocking the power of RWD/RWE. [ABSTRACT FROM AUTHOR]

Objective: Whether coal mine dust exposure increases cardiovascular diseases (CVDs) risk was rarely explored. Our objective was to examine the association between coal mine dust exposure and cardiovascular risk. Methods: We estimated cumulative coal mine dust exposure (CDE) for 1327 coal miners by combining data on workplace dust concentrations and work history. We used brachial-ankle pulse wave velocity (baPWV, a representative indicator of arterial stiffness) and ten-year atherosclerotic cardiovascular disease (ASCVD) risk to assess potential CVD risk, exploring their associations with CDE. Results: Positive dose-response relationships of CDE with baPWV and ten-year ASCVD risk were observed after adjusting for covariates. Specifically, each 1 standard deviation (SD) increase in CDE was related to a 0.27 m/s (95% CI: 0.21, 0.34) increase in baPWV and a 1.29 (95% CI: 1.14, 1.46) elevation in OR (odds ratio) of risk of abnormal baPWV. Moreover, each 1 SD increase in CDE was associated with a 0.74% (95% CI: 0.63%, 0.85%) increase in scores of ten-year ASCVD and a 1.91 (95% CI: 1.62, 2.26) increase in OR of risk of ten-year ASCVD. When compared with groups unexposed to coal mine dust, significant increase in the risk of arterial stiffness and ten-year ASCVD in the highest CDE groups were detected. Conclusion: The study suggested that cumulative exposure to coal mine dust was associated with elevated arterial stiffness and ten-year ASCVD risk in a dose-response manner. These findings contribute valuable insights for cardiovascular risk associated with coal mine dust. [ABSTRACT FROM AUTHOR]

Two new stilbenes, 5-methoxy-6-(4-methoxystyryl)-3-methylbenzofuran (1) and 5-methoxy-6-(4- hydroxystyryl)-3-methylbenzofuran (2), together with six known ones, bauhiniastatin D (3), gramideoxybenzoin B (4), gramistilbenoid A (5), gramistilbenoid B (6), gramniphenol H (7), and pterostilbene (8), were isolated from the whole plants of Arundina graminifolia. Their structures were established by their 1D, 2D NMR, and MS spectral data. Compounds 1 and 2 were tested for their anti-SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) activity. The results revealed that compound 1 exhibited potential activity with IC50 of 17.4 μM for delta strain and 28.5 μM for Omicron BA.1 strain, compound 2 also showed potential activity with IC50 of 15.3 μM for delta strain and 22.6 μM for Omicron BA.1 strain, respectively. [ABSTRACT FROM AUTHOR]

To evaluate the potential ecotoxicity of ethiprole and early warning to earthworms (Eisenia fetida), different concentrations (0 mg·kg−1, 416 mg·kg−1, 625 mg·kg−1, and 1000 mg·kg−1) of ethiprole were added to artificial soil. The key bioindicators were measured and screened at 3 days, 7 days, 14 days, 21 days, and 28 days. The results show that the activity of catalase (CAT) was inhibited for all treatments during the whole exposure period. Besides, the olive tail moment (OTM) value increased gradually as the concentration got higher, which exhibited a dose-time-dependent relationship. Superoxide dismutase (SOD) gene reached the maximum on the 7th day. Mitochondrial large ribosomal RNA (l-rRNA) subunit gene was always in a downregulated state as the concentration increased. Our results show that different concentrations of ethiprole induced certain oxidative stress, DNA damage, and genotoxicity in earthworms. The CAT activity, OTM, and SOD gene could be the most sensitive biomarkers to monitor the toxicity of ethiprole in the soil. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effect of intraperitoneal infusion of ropivacaine combined with dexmedetomidine and ropivacaine alone on the quality of postoperative recovery of patients undergoing total laparoscopic hysterectomy (TLH). Methods: Female patients scheduled to undergo a TLH under general anesthesia at Fujian Maternity and Child Health Hospital were included. Before the end of pneumoperitoneum, patients were laparoscopically administered an intraperitoneal infusion of 0.25% ropivacaine 40 ml (R group) or 0.25% ropivacaine combined with 1 µg/kg dexmedetomidine 40 ml (RD group). The primary outcome was QoR-40, which was assessed before surgery and 24 h after surgery. Secondary outcomes included postoperative NRS scores, postoperative anesthetic dosage, the time to ambulation, urinary catheter removal, and anal exhaust. The incidence of dizziness, nausea, and vomiting was also analyzed. Results: A total of 109 women were recruited. The RD group had higher QoR scores than the R group at 24 h after surgery (p < 0.05). Compared with the R group, NRS scores in the RD group decreased at 2, 6, 12, and 24 h after surgery (all p < 0.05). In the RD group, the time to the first dosage of postoperative opioid was longer and the cumulative and effective times of PCA compression were less than those in the R group (all p < 0.05). Simultaneously, the time to ambulation (p = 0.033), anal exhaust (p = 0.002), and urethral catheter removal (p = 0.018) was shortened in the RD group. The RD group had a lower incidence of dizziness, nausea, and vomiting (p < 0.05). Conclusion: Intraperitoneal infusion of ropivacaine combined with dexmedetomidine improved the quality of recovery in patients undergoing TLH. Trial registration: ChiCTR2000033209, Registration Date: May 24, 2020. [ABSTRACT FROM AUTHOR]

Digital collections, loved and valued by the public, have become a new trend in cultural tourism consumption. Their ultimate aim is to boost cultural tourism consumption and empower offline tourism. This study constructs a theoretical model of "digital collectibles involvement (DCI)-perceived value (PV)-tourist intention to visit on site (TIVS)" based on the theory of involvement and Stimulus-Organism-Response (SOR). It empirically investigates the influence of DCI on TIVS. The study found that digital collection involvement has a significant positive influence on tourists' intentions to visit on-site, and the positive impact of digital collectibles' persistent involvement on TIVS is higher than digital collectibles' contextual involvement. Perceived value plays a fully mediating role in the relationship between DCI and TIVS. Visual perception is a positive moderator in the relationship between DCI and TIVS. The moderating effect of cultural attributes was not significant. The research conclusion provides a theoretical reference for the development of offline tourism by using digital collectibles. [ABSTRACT FROM AUTHOR]

Faculty supervisor profiles on the graduate school webpages of universities offer an explicit assertion of self-representation regarding the author's academic identity, from which potential graduates can gain official information about their future faculty supervisors. Though scholars' identity construction on blogs or homepages has drawn sufficient attention, supervisors' identity construction on graduate school webpages across authors' status, gender, and disciplines in the Chinese context has not been sufficient. Based on the analysis of moves and processes, this study explores academic identity construction across authors' status, gender, and disciplines. Professor/Ph.D. faculty supervisors (PPSs) generally tend to use more moves than associate professors/master supervisors (APMs); different relational and material processes are used most frequently for scholars of different statuses. For gender, male academics use more words than females for move and process items. For disciplinary differences, art scholars pay close attention to education, achievement and community service, presenting more relational processes, while history and telecommunications scholars concentrate on their research directions and main publications. The results are further discussed with reference to status advantage, women's dilemma, and disciplinary culture in the Chinese academic community. [ABSTRACT FROM AUTHOR]

Photocatalytic water splitting (PWS) as the holy grail reaction for solar-to-chemical energy conversion is challenged by sluggish oxygen evolution reaction (OER) at water/catalyst interface. Experimental evidence interestingly shows that temperature can significantly accelerate OER, but the atomic-level mechanism remains elusive in both experiment and theory. In contrast to the traditional Arrhenius-type temperature dependence, we quantitatively prove for the first time that the temperature-induced interface microenvironment variation, particularly the formation of bubble-water/TiO2(110) triphase interface, has a drastic influence on optimizing the OER kinetics. We demonstrate that liquid-vapor coexistence state creates a disordered and loose hydrogen-bond network while preserving the proton transfer channel, which greatly facilitates the formation of semi-hydrophobic •OH radical and O-O coupling, thereby accelerating OER. Furthermore, we propose that adding a hydrophobic substance onto TiO2(110) can manipulate the local microenvironment to enhance OER without additional thermal energy input. This result could open new possibilities for PWS catalyst design.Temperature has demonstrated the potential to regulate the photocatalytic oxygen evolution reaction (OER). This study confirms that the temperature-induced bubble-water/catalyst triphase interface microenvironment significantly enhances OER by optimizing the formation and deprotonation of semi-hydrophobic OH radicals. [ABSTRACT FROM AUTHOR]

The rapid development of artificial intelligence poses an urgent need for low-energy-consumption and small-sized artificial photonic synapses. Here, it is pretty novel to demonstrate a light-stimulated synaptic device based on a single (Al,Ga)N nanowire successfully. Thanks to the presence of vacancy defects in the single nanowire, the artificial synaptic device can simulate multiple functions of biological synapses under stimulation of both 310 and 365 nm light photons, including paired-pulse facilitation, spike timing dependent plasticity, and memory learning capabilities. The energy consumption of artificial synaptic device can be reduced as little as 5.58 × 10−13 J, which is close to that of the biological synapse in human brain. Furthermore, the synaptic device is demonstrated to have the high stability for both long-time stimulation and long-time storage. Based on the experimental conductance of long-term potentiation and long-term depression, the simulated three-layer neural network can achieve a high recognition rate of 92% after only 10 training epochs. With a brain-like behavior, the single-nanowire-based synaptic devices can promote the development of visual neuromorphic computing technology and artificial intelligence systems requiring ultralow energy consumption. [ABSTRACT FROM AUTHOR]

With the aim of screening more bioactivity metabolites, in this study, two new stilbenes, 5-methoxy-6-(4- methoxystyryl)benzofuran (1) and 6-(4-methoxystyryl)benzofuran-5-ol (2) were isolated from the leaves and stems of Bletilla striata. Their structures were established by their 1D, 2D NMR, and MS spectral data. Interestingly, the anti-SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) activity revealed that compound 1 exhibited potential anti-SARS-CoV-2 activity with IC50 of 15.2 μM for the delta strain and 22.8 μM for the omicron BA.1 strain; compound 2 also showed potential anti-SARS-CoV-2 activity with IC50 of 10.2 μM for the delta strain and 16.8 μM for the omicron BA.1 strain. These values are lower than that of a positive control (with IC50 of 1.2 μM for the delta strain and 3.4 μM for the omicron BA.1 strain). [ABSTRACT FROM AUTHOR]

Background: Various genetic and nongenetic variables influence the high on-treatment platelet reactivity (HTPR) in patients taking clopidogrel. Aim: This study aimed to develop a novel machine learning (ML) model to predict HTPR in Chinese patients after percutaneous coronary intervention (PCI). Method: This cohort study collected information on 507 patients taking clopidogrel. Data were randomly divided into a training set (90%) and a testing set (10%). Nine candidate Machine learning (ML) models and multiple logistic regression (LR) analysis were developed on the training set. Their performance was assessed according to the area under the receiver operating characteristic curve, precision, recall, F1 score, and accuracy on the test set. Model interpretations were generated using importance scores by transforming model variables into scaled features and representing in radar plots. Finally, we established a prediction platform for the prediction of HTPR. Results: A total of 461 patients (HTPR rate: 19.52%) were enrolled in building the prediction model for HTPR. The XGBoost model had an optimized performance, with an AUC of 0.82, a precision of 0.80, a recall of 0.44, an F1 score of 0.57, and an accuracy of 0.87, which was superior to those of LR. Furthermore, the XGBoost method identified 7 main predictive variables. To facilitate the application of the model, we established an XGBoost prediction platform consisting of 7 variables and all variables for the HTPR prediction. Conclusion: A ML-based approach, such as XGBoost, showed optimum performance and might help predict HTPR on clopidogrel after PCI and guide clinical decision-making. Further validated studies will strengthen this finding. [ABSTRACT FROM AUTHOR]

Purpose: Cytokeratin 19-positive cancer stem cells (CK19 + CSCs) and their tumor-associated macrophages (TAMs) have not been fully explored yet in the hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Experimental design: Single-cell RNA sequencing was performed on the viable cells obtained from 11 treatment-naïve HBV-associated HCC patients, including 8 CK19 + patients, to elucidate their transcriptomic landscape, CK19 + CSC heterogeneity, and immune microenvironment. Two in-house primary HCC cohorts (96 cases-related HBV and 89 cases with recurrence), TCGA external cohort, and in vitro and in vivo experiments were used to validate the results. Results: A total of 64,581 single cells derived from the human HCC and adjacent normal tissues were sequenced, and 11 cell types were identified. The result showed that CK19 + CSCs were phenotypically and transcriptionally heterogeneous, co-expressed multiple hepatics CSC markers, and were positively correlated with worse prognosis. Moreover, the SPP1 + TAMs (TAM_SPP1) with strong M2-like features and worse prognosis were specifically enriched in the CK19 + HCC and promoted tumor invasion and metastasis by activating angiogenesis. Importantly, matrix metalloproteinase 9 (MMP9) derived from TAM_SPP1, as the hub gene of CK19 + HCC, was activated by the VEGFA signal. Conclusions: This study revealed the heterogeneity and stemness characteristics of CK19 + CSCs and specific immunosuppressive TAM_SPP1 in CK19 + HCC. The VEGFA signal can activate TAM_SPP1-derived MMP9 to promote the invasion and metastasis of CK19 + HCC tumors. This might provide novel insights into the clinical treatment of HCC patients. Lay summary: Cytokeratin 19-positive hepatocellular carcinoma is a highly aggressive malignancy with poor therapeutic progress. Understanding the characteristics of CK19 + CSCs and their immune microenvironment better might facilitate the development of effective targeted and immunotherapy. This study identified the heterogeneity and characteristics of CK19 + CSCs and explored their unique immunosuppressive SPP1+TAM niche. The results suggested that the VEGFA signal activates TAM_SPP1-derived MMP9 to promote the invasion and metastasis of CK19 + HCC tumors. The study might have an important therapeutic value. [ABSTRACT FROM AUTHOR]

We aimed to investigate the safety and efficacy of nirmatrelvir/ritonavir (Paxlovid) therapy for hemodialysis-dependent patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Thirteen hemodialysis patients infected with the Omicron variant of SARS-CoV-2 from April 3 to May 30, 2022, were recruited. Laboratory parameters and chest CT (computed tomography) imaging were analyzed. The treatment group included six patients who received 150 mg/100 mg of Paxlovid orally once daily for 5 days, whereas the control group included seven patients who received basic treatment. No serious adverse reactions or safety events were recorded. Four control patients progressed to moderate disease, and none in the treatment group showed progression of chest CT findings (P < 0.05). Paxlovid therapy tended toward early viral clearance and low viral load on Day 8. Moreover, 83.3% of the patients in the treatment group and 57.1% of the patients in the control group turned negative within 22 days. In the Paxlovid treatment group, we found significantly increased levels of lymphocytes (P=0.03) and eosinophils (P=0.02) and decreased levels of D-dimer on Day 8 compared with those on Day 1. Paxlovid therapy showed a potential therapeutic effect with good tolerance in hemodialysis patients. The optimal dose and effectiveness evaluation must be further investigated in a largeer cohort. [ABSTRACT FROM AUTHOR]

The CaO-B2O3-SiO2 (CBS) glass-ceramics with different B2O3 content were prepared by glass melt quenching followed by sintering method. The crystallization behavior and dielectric properties of CBS glass-ceramics were systemically investigated. The thermal properties and flexural strength of CBS glass-ceramics were also characterized. Results show that the main crystal phases of each composition are CaSiO3, SiO2 and CaB2O4. Quantitative analysis of the crystal phase found that B2O3 content stimulates the formation of CaB2O4 phase but inhibits the generation of CaSiO3 phase. In addition, the B2O3 content also acts on the properties of CBS glass-ceramics. In this study, the 41CaO-41SiO2-18B2O3 (mol%) sample sintered at 900 °C for 15 min has the optimum properties: the density of 2.65 g/cm3, a moderate dielectric constant of 6.13, a low dielectric loss of 1.6 × 10–3 (10 GHz), the thermal expansion coefficient of 8.79 ppm/K, the thermal conductivity of 2.85 W/m/K, a high flexural strength of 191.0 MPa. Such glass-ceramics with high flexural strength and excellent dielectric properties have good development prospect for LTCC applications. [ABSTRACT FROM AUTHOR]

Highlights: The latest advancements in Cu-based catalysts for photocatalytic and electrocatalytic CO2 reduction into C2+ products are reported. The relationship between the Cu surfaces and their efficiency in photocatalytic and electrocatalytic CO2 reduction is emphasized. The opportunities and challenges associated with Cu-based materials in the CO2 catalytic reduction applications are presented. Carbon dioxide conversion into valuable products using photocatalysis and electrocatalysis is an effective approach to mitigate global environmental issues and the energy shortages. Among the materials utilized for catalytic reduction of CO2, Cu-based materials are highly advantageous owing to their widespread availability, cost-effectiveness, and environmental sustainability. Furthermore, Cu-based materials demonstrate interesting abilities in the adsorption and activation of carbon dioxide, allowing the formation of C2+ compounds through C–C coupling process. Herein, the basic principles of photocatalytic CO2 reduction reactions (PCO2RR) and electrocatalytic CO2 reduction reaction (ECO2RR) and the pathways for the generation C2+ products are introduced. This review categorizes Cu-based materials into different groups including Cu metal, Cu oxides, Cu alloys, and Cu SACs, Cu heterojunctions based on their catalytic applications. The relationship between the Cu surfaces and their efficiency in both PCO2RR and ECO2RR is emphasized. Through a review of recent studies on PCO2RR and ECO2RR using Cu-based catalysts, the focus is on understanding the underlying reasons for the enhanced selectivity toward C2+ products. Finally, the opportunities and challenges associated with Cu-based materials in the CO2 catalytic reduction applications are presented, along with research directions that can guide for the design of highly active and selective Cu-based materials for CO2 reduction processes in the future. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate changes in retinal and choroidal vascularity using swept-source optical coherence tomography (SS-OCT) and optical coherence tomography angiography (OCTA) in patients with systemic lupus erythematosus (SLE). Methods: In this prospective, cross-sectional study, 48 SLE patients and 40 healthy control (group HC) participants were included. The SLE patients were divided into two subgroups: patients with SLE with no ocular disease (group I) and patients with SLE with signs of retinopathy (group II). The superficial vessel density (SVD), deep vessel density (DVD), peripapillary retinal vessel densities (pRVD), choroidal thickness (ChT), and choroidal vascularity including total choroidal area (TCA), luminal area (LA), stromal area (SA), and choroidal vascularity index (CVI) were measured using SS-OCT/OCTA. Physical and ophthalmic examinations as well as the assessments of immunological markers were performed. The results of SS-OCT/OCTA were compared between group I, group II, and group HC, while the correlations among the parameters were analyzed. Results: The SVD, DVD, and pRVD were found to be significantly lower in SLE patients than group HC, especially in SLE patients with signs of retinopathy. ChT were found to be significantly higher in group II. CVI was positively correlated with SVD and DVD in the fovea, as well as the foveal and parafoveal thickness. A significant decrease in SVD and DVD in the fovea among subjects positive for anti-dsDNA antibodies was noted. Conclusions: The application of OCTA in the evaluation of microvasculature may be useful in subclinical changes. Retinal microvascular density decreased in patients with SLE with greater severity of SLE. Disturbed retinal circulation was related to SLE disease activity, disease duration, CVI, and being positive for anti-dsDNA antibodies. The study results also suggest that SLE with signs of retinopathy may affect the choroid with increases in LA, SA, TCA, and ChT. [ABSTRACT FROM AUTHOR]

Overcoming multidrug resistance (MDR) represents a major obstacle in cancer chemotherapy. Cardiac glycosides (CGs) are efficient in the treatment of heart failure and recently emerged in a new role in the treatment of cancer. ZINC253504760, a synthetic cardenolide that is structurally similar to well-known GCs, digitoxin and digoxin, has not been investigated yet. This study aims to investigate the cytotoxicity of ZINC253504760 on MDR cell lines and its molecular mode of action for cancer treatment. Four drug-resistant cell lines (P-glycoprotein-, ABCB5-, and EGFR-overexpressing cells, and TP53-knockout cells) did not show cross-resistance to ZINC253504760 except BCRP-overexpressing cells. Transcriptomic profiling indicated that cell death and survival as well as cell cycle (G2/M damage) were the top cellular functions affected by ZINC253504760 in CCRF-CEM cells, while CDK1 was linked with the downregulation of MEK and ERK. With flow cytometry, ZINC253504760 induced G2/M phase arrest. Interestingly, ZINC253504760 induced a novel state-of-the-art mode of cell death (parthanatos) through PARP and PAR overexpression as shown by western blotting, apoptosis-inducing factor (AIF) translocation by immunofluorescence, DNA damage by comet assay, and mitochondrial membrane potential collapse by flow cytometry. These results were ROS-independent. Furthermore, ZINC253504760 is an ATP-competitive MEK inhibitor evidenced by its interaction with the MEK phosphorylation site as shown by molecular docking in silico and binding to recombinant MEK by microscale thermophoresis in vitro. To the best of our knowledge, this is the first time to describe a cardenolide that induces parthanatos in leukemia cells, which may help to improve efforts to overcome drug resistance in cancer. A cardiac glycoside compound ZINC253504760 displayed cytotoxicity against different multidrug-resistant cell lines. ZINC253504760 exhibited cytotoxicity in CCRF-CEM leukemia cells by predominantly inducing a new mode of cell death (parthanatos). ZINC253504760 downregulated MEK1/2 phosphorylation and further affected ERK activation, which induced G2/M phase arrest. [ABSTRACT FROM AUTHOR]

Peanut (Arachis hypogaea L.) is an important global food crop, providing a valuable source of protein, oil and nutrition. The functional analysis of genes associated with yield traits is an important step in molecular breeding, which requires effective methods of genetic transformation. In this study, we applied the CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 system in conjunction with Agrobacterium tumefaciens-mediated pollen tube transformation to create knockout mutants of the peanut MUTATOR-LIKE TRANSPOSABLE ELEMENT9A (AhMULE9A) gene, which plays an importantly regulatory role in response to Al stress in peanut. The gene mutations were identified by the analysis of genomic sequences flanking the sgRNA target sites. The sequencing of AhMULE9A mutations showed that eleven of the fifteen transgenics produced resulted in protein sequence changes, demonstrating the efficacy of this method for the production of targeted mutations in allotetraploid peanut. Key message: This study highlights the efficiency and utility of CRISPR/Cas9 gene editing in peanut in conjunction with Agrobacterium tumefaciens-mediated pollen tube transformation. [ABSTRACT FROM AUTHOR]

Vibrio parahaemolyticus, the causative agent of seafood-associated gastroenteritis, undergoes wrinkly and smooth colony switching on the plate. The wrinkly spreader grew faster, had stronger motility and biofilm capacity when compared with the smooth one. However, whether the two phenotypes differ in their virulence still needs to be further investigated. In this study, the data showed that the smooth spreader had stronger virulence phenotypes, including the cytotoxicity against HeLa cells, antibacterial activity against E. coli, adhesive capacity toward HeLa cells, and lethality in zebrafish, relative to the wrinkly one. However, the colony morphology variation had no influence on the haemolytic activity. The mRNA levels of major virulence genes including T3SS1, T6SS1, and T6SS2 were significantly enhanced in the smooth colonies relative to those in the wrinkly colonies. Taken together, the presented work highlighted the different virulence profiles of the wrinkly and smooth colony phenotypes. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported at the end of 2019 as a worldwide health concern causing a pandemic of unusual viral pneumonia and many other organ damages, which was defined by the World Health Organization as coronavirus disease 2019 (COVID-19). The pandemic is considered a significant threat to global public health till now. In this review, we have summarized the lessons learnt during the emergence and spread of SARS-CoV-2, including its prototype and variants. The overall clinical features of variants of concern (VOC), heterogeneity in the clinical manifestations, radiology and pathology of COVID-19 patients are also discussed, along with advances in therapeutic agents. [ABSTRACT FROM AUTHOR]

Background: Tobacco mosaic virus (TMV) is a harmful plant pathogen that causes a decline in the quality and yield of many economic crops. Natural products are important potential sources of biopesticides for the prevention and treatment of TMV. This study focuses on the discovery of anti-TMV active compounds from Aspergillus versicolor and investigates their activities against TMV. Results: In this study, four isocoumarins 7-methoxy-3-(2-oxopropy)-5-hydroxymethyl-isocoumarin (1), 7-methyl-3-(2-oxopropy)-5-hydroxymethyl-isocoumarin (2), oryzaein A (4) and oryzaein B (5), two indole alkaloids aspergilline F (6) and aspergilline G (7), and one indole alkaloid and isocoumarin hybrid aspergillactone A (3) were isolated from Nicotiana tabacum-derived A. versicolor YNCA0363. Among them, compounds 1–3 are new isolates, compound 3 represents the first example of indole alkaloid and isocoumarin connected by C(12)-N(1′) bond. The inactivation efficacies for compounds 1, 2 and 3 were 58.9, 43.8 and 52.6% at the concentration of 50 μg/mL, respectively, which were significantly higher than that of positive control, ningnanmycin. The protective effects of these three compounds ranged from 48.6 to 62.3%, which were significantly higher than that of positive control. At the same time, the content of TMV-CP was also significantly lower than that of positive control, and compound 1 was the lowest. The curative efficacy for compound 1 was also much better than that of positive control. Transmission electron microscopy (TEM) showed that compound 1 could directly destroy viral particles into small fragments. The results of molecular docking showed that the binding ability of compounds 1, 3, 2 to TMV-CP protein decreased in turn, which was consistent with the results of activities assays. Conclusion: Compounds 1–3 from A. versicolor showed potent antiviral activities against TMV including inactivation, protective and curative effects. Compound 1 can directly destroy the virus particles to achieve the effect of anti-TMV. In addition, compounds 1–3 can bind to TMV-CP protein in molecular docking experiments. The above experimental results show that TMV-CP was an important target for active indole alkaloid and isocoumarin derivatives to fracture TMV particle. The results provided evidence that indole alkaloid and isocoumarin derivatives from A. versicolor have the potential to control TMV. [ABSTRACT FROM AUTHOR]

Background: Inflammatory adipokines and cytokines play a pivotal role in linking obesity and breast cancer (BC) risk in women. We investigated the longitudinal associations between BMI change and trajectories of inflammatory biomarkers related to BC risk. Methods: A longitudinal study was conducted among 442 Chinese women with 3-year repeated measures from 2019 to 2021. Plasma circulating inflammatory biomarkers related to BC risk, including adiponectin (ADP), resistin (RETN), soluble leptin receptor (sOB-R), insulin-like growth factor-binding protein-3 (IGFBP-3), and C-reactive protein (CRP), were examined annually. Linear mixed-effect models (LMM) were applied to investigate associations of time-varying BMI with trajectories of biomarkers. We additionally examined the modification effect of baseline BMI groups, menopausal status, and metabolic syndrome. Results: BMI was associated with increased levels of RETN, CRP, sOB-R, and decreased levels of ADP at baseline. An increasing BMI rate was significantly associated with an average 3-year increase in RETN (β = 0.019, 95% CI 0.004 to 0.034) and sOB-R (β = 0.022, 95% CI 0.009 to 0.035), as well as a decrease in ADP (β = − 0.006, 95% CI − 0.012 to 0.001). These associations persisted across different baseline BMI groups. An increasing BMI rate was significantly associated with an average 3-year increase in CRP levels among normal weight (β = 0.045, 95% CI 0.001 to 0.088) and overweight (β = 0.060, 95% CI 0.014 to 0.107) women. As BMI increased over time, a more remarkable decrease in ADP was observed among women with metabolic syndrome (β = − 0.016, 95% CI − 0.029 to − 0.004) than those without metabolic syndrome at baseline. Conclusions: A higher increase rate of BMI was associated with poorer trajectories of inflammatory biomarkers related to BC risk. Recommendations for BMI reduction may benefit BC prevention in women, particularly for those with metabolic syndrome. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the ability of neurite orientation dispersion and density imaging (NODDI) for detecting white matter (WM) microstructural abnormalities in minimal hepatic encephalopathy (MHE). Methods: Diffusion-weighted images, enabling the estimation of NODDI and diffusion tensor imaging (DTI) parameters, were acquired from 20 healthy controls (HC), 22 cirrhotic patients without MHE (NHE), and 15 cirrhotic patients with MHE. Tract-based spatial statistics were used to determine differences in DTI (including fractional anisotropy [FA] and mean/axial/radial diffusivity [MD/AD/RD]) and NODDI parameters (including neurite density index [NDI], orientation dispersion index [ODI], and isotropic volume fraction [ISO]). Voxel-wise analyses of correlations between diffusion parameters and neurocognitive performance determined by Psychometric Hepatic Encephalopathy Score (PHES) were completed. Results: MHE patients had extensive NDI reduction and rare ODI reduction, primarily involving the genu and body of corpus callosum and the bilateral frontal lobe, corona radiata, external capsule, anterior limb of internal capsule, temporal lobe, posterior thalamic radiation, and brainstem. The extent of NDI and ODI reduction expanded from NHE to MHE. In both MHE and NHE groups, the extent of NDI change was quite larger than that of FA change. No significant intergroup difference in ISO/MD/AD/RD was observed. Tissue specificity afforded by NODDI revealed the underpinning of FA reduction in MHE. The NDI in left frontal lobe was significantly correlated with PHES. Conclusion: MHE is characterized by diffuse WM microstructural impairment (especially neurite density reduction). NODDI can improve the detection of WM microstructural impairments in MHE and provides more precise information about MHE-related pathology than DTI. [ABSTRACT FROM AUTHOR]

Background: Iodine is an essential element for the biosynthesis of thyroid-stimulating hormone (TSH). Both excessive and deficient iodine are major risk factors for thyroid diseases, including thyroid dysfunction, thyroid nodules, and thyroid autoimmunity (TAI). This study aimed to elucidate the relationship between iodine status and the prevalence of thyroid diseases through a national cross-sectional epidemiological survey in Jiangxi province (China). Methods: This population-based, cross-sectional study enrolled 2636 Chinese local inhabitants who aged over 18 years old from April to August in 2015. Physical examination was performed and biochemical indices, urinary iodine concentration (UIC), and TSH level were measured. The Chi-square test, nonparametric test, and 4 multivariate logistic regression models adjusted for risk factors were applied to analysis. Spearman correlation coefficients were calculated to investigate the relationship between iodine intake level and the prevalence of thyroid diseases. Results: The median UIC was 176.4 μg/L, and a significant difference was found in median UIC between men (182.45 μg/L) and women (169.25 μg/L) (P = 0.03). Among these study subjects, 14.4%, 44.5%, 26.1%, and 15.0% had deficient, adequate, more than adequate, and excessive iodine concentrations, respectively. The prevalence rates of hyperthyroidism, subclinical hyperthyroidism, hypothyroidism, subclinical hypothyroidism, thyroid nodules, and TAI were 0.91%, 0.57%, 0.34% and 7.89%, 9.45%, and 12.7%, respectively. Significant differences were found in iodine status, waist circumstance, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), TSH, thyroid nodules, and TAI between men and women (P < 0.05). Compared with those with adequate UIC, subjects with excessive UIC had higher prevalence rates of thyroid dysfunction (odds ratio (OR) = 1.74, 95% confidence interval (CI): 1.40–2.54) and thyroid nodules (OR = 3.33, 95%CI 1.32–8.42). In addition, subjects with deficient and excessive UIC were at the higher risk of TAI compared with those with adequate UIC (OR = 1.68, 95%CI: 1.19–2.60; OR = 1.52, 95%CI: 1.04–2.96, respectively). UIC was positively correlated with the prevalence rates of thyroid nodules (r = −0.44, P < 0.01) and TAI (r = −0.055, P < 0.01). On the contrary, UIC was negatively correlated with the risk of thyroid dysfunction (r = −0.24, P > 0.05). Conclusion: Adult inhabitants from Jiangxi province in the TIDE study were in the adequate iodine status. Excessive iodine status was noted as a risk factor for thyroid dysfunction and thyroid nodules. In addition, both iodine deficiency and excessive iodine were risk factors for TAI. [ABSTRACT FROM AUTHOR]

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Purpose: This meta-analysis aims to evaluate the therapeutic efficacy of anterior versus posterior surgical approaches for multisegment cervical spondylotic myelopathy (MCSM). Methods: Eligible studies published between the period of January 2001 and April 2022 and comparing the anterior and posterior surgical approaches for treating cervical spondylotic myelopathy were retrieved from the PubMed, Web of Science, Embase, and Cochrane databases. Results: A total of 17 articles were selected based on the inclusion and exclusion criteria. This meta-analysis failed to show any significant difference in the duration of surgery, the hospitalization time, or the improvement in the Japanese Orthopedic Association score between the anterior and posterior approaches. The anterior approach, however, exhibited increased efficacy in the improvement of the neck disability index, reduction in the visual analog scale for cervical pain, and improvement in the cervical curvature compared with the posterior approach. Conclusion: Bleeding was also less with the anterior surgical approach. The posterior approach provided a significantly higher range of motion of the cervical spine and showed fewer postoperative complications compared with the anterior approach. While both the surgical approaches have good clinical outcomes and show postoperative neurological function improvement, the meta-analysis shows that both anterior and posterior approaches have certain merits and shortcomings. A meta-analysis of a larger number of randomized controlled trials with longer follow-up can conclusively determine which of the surgical approaches is more beneficial in the treatment of MCSM. [ABSTRACT FROM AUTHOR]

In this paper, the authors discuss an optimal control problem of a reaction-diffusion leukemia immune model that describes the dynamics of leukemia cells, normal cells, and CAR-T cells. In order to overcome the defects of traditional biotherapy for leukemia by injecting CAR-T cells in a large dose at one time, dynamic low-dose injection of CAR-T cells is considered in this paper. To minimize the total amount of leukemia cells and the injection amount of CAR-T cells and to maximize the total amount of normal cells, an optimal control problem is proposed. We first show the existence, uniqueness, and some estimates of the positive strong solution to the controlled system by using semigroup and functional analysis techniques. Then, the existence of the optimal control is proved by employing minimal sequence methods. On this basis, we further give the first-order necessary conditions satisfied by the optimal control strategy by using the convex perturbation and dual methods. Finally, a specific example and its numerical implementation are offered, which further confirm the theoretical results. [ABSTRACT FROM AUTHOR]

Background: Personalisation strategies of ovarian stimulation for in vitro fertilisation (IVF)/ intracytoplasmic sperm injection (ICSI) treatments using exogenous follicle-stimulating hormone (FSH) have been extensively studied over the past 20 years. This research aimed to develop a FSH population pharmacokinetic (PPK) model taking into account the contribution of gene polymorphisms in Chinese reproductive-age women. Methods: Data from 173 patients undergoing GnRH agonist down-regulation long protocols of IVF/ICSI treatment were collected. PPK analysis was subsequently conducted using the nonlinear mixed-effect model (NONMEM) software. Several covariates, including 18 single nucleotide polymorphisms, demographic factors and biological characteristics, were evaluated. The final PPK model was extensively validated using bootstrapping and normalised prediction error distribution, as well as external validation on an independent group of 35 patients. Results: FSH PPK was accurately described by a one-compartment model with first-order absorption. The typical population value of apparent clearance was estimated to be 0.81 L/h [relative standard errors (RSE) 5.3%] with an inter-individual variability (IIV) of 16.0%. The typical apparent distribution volume was 8.36 L (RSE 9.7%, 59.7% IIV), and the absorption rate constant was estimated to be 0.0444 h−1 (RSE 9.1%). Body weight, basal prolactin concentration and the gene ADIPOQ (rs1501299) showed a significant covariate effect on the FSH clearance rate and exposure concentration. Genotypes of THADA (rs12478601) significantly influenced the distribution volume. Simulation results indicated that patients with the TT genotype of THADA (rs12478601) required a longer time to reach steady state and had less fluctuation in FSH levels. Model evaluations showed that the final model accurately and precisely described the observed data and demonstrated effective prediction performance. Conclusion: PPK models of FSH have been developed, which could potentially be used for FSH dosage individualisation in the clinical setting. Clinical trial registration: This study has been registered with the Chinese Clinical Trials Registry (ChiCTR2100049142). [ABSTRACT FROM AUTHOR]