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Mitochondria are essential organelles that not only undergo dynamic morphological changes but also exhibit functional activities such as mitochondrial membrane potential (MMP). While super-resolution techniques such as stimulated emission depletion (STED) nanoscopy can visualize the ultrastructure of mitochondria and the MMP probe can monitor mitochondria function, few dyes meet both demands. Here, a small molecule (MitoPDI-90) based on perylene diimide with cationic groups is reported and used for mitochondrial STED imaging and MMP indication. Characterized by excellent photostability, biocompatibility, and high quantum yield, MitoPDI-90 exhibits STED imaging compatibility, facilitating visualization of mitochondrial cristae and time-lapse imaging of highly dynamic mitochondria in living cells. Besides, MitoPDI-90 targets the mitochondria through electrical potential, also enabling live-cell MMP monitoring. MitoPDI-90 allows for super-resolution visualization and time-lapse imaging of mitochondria, and more importantly, indication of changes in MMP, providing insight into the functional activity of live-cell mitochondria., (© 2024 Wiley‐VCH GmbH.)

Background: Evidence has demonstrated that visceral fat area (VFA) and subcutaneous fat area (SFA) had different influences on cardiovascular disease (CVD) risk in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate the relationship between the visceral fat area (VFA) to subcutaneous fat area (SFA) ratio (V/S) and carotid atherosclerosis (CAS) in patients with T2DM., Methods: From January 2018 to May 2023, 1,838 patients with T2DM admitted to the National Metabolic Management Centre in our hospital were assigned to two groups based on comorbid CAS. Dual bioelectrical impedance analysis was used to measure the VAF and SFA, and the V/S was calculated. Patient characteristics and serum biochemical indices were compared between groups. Factors influencing comorbid CAS were determined, and correlations between V/S and other clinical indices were analyzed., Results: The group with comorbid CAS included 858 individuals and 980 without comorbid CAS. Those with comorbid CAS were older and had a longer disease duration, more significant systolic blood pressure, and greater V/S. The proportions of patients with comorbid hypertension increased significantly with the V/S ratio. The V/S ratio positively correlated with triglyceride (TG), low-density lipoprotein cholesterol levels, and waist circumference. According to binary logistic regression analysis, V/S was an independent risk factor for CAS., Conclusion: Elevated V/S is an independent risk factor for CAS in patients with T2DM.

Essential oils (EO), secondary metabolites of plants are fragrant oily liquids with antibacterial, antiviral, anti-inflammatory, anti-allergic, and antioxidant effects. They are widely applied in food, medicine, cosmetics, and other fields. However, the quality of EOs remain uncertain owing to their high volatility and susceptibility to oxidation, influenced by factors such as the harvesting season, extraction, and separation techniques. Additionally, the huge economic value of EOs has led to a market marked by widespread and varied adulteration, making the assessment of their quality challenging. Therefore, developing simple, quick, and effective identification techniques for EOs is essential. This review comprehensively summarizes the techniques for assessing EO quality and identifying adulteration. It covers sensory evaluation, physical and chemical property evaluation, and chemical composition analysis, which are widely used and of great significance for the quality evaluation and adulteration detection of EOs., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that may have influenced the work reported in this study., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background and Aim: The TyG index has been linked with cardiometabolic diseases. Our study aimed to investigate the specific relationship between the triglyceride and glucose index (TyG) and both all-cause and cardiovascular mortality in diabetic patients., Methods and Results: We enrolled 3120 participants with diabetes from the National Health and Nutrition Examination Survey. The TyG index was calculated using the formula ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Hazard ratios (HRs) of TyG associated with mortality risk were assessed using Cox proportional hazard regression models. Over a follow-up period of 10.8 thousand person-years, we observed 768 all-cause deaths and 155 cardiovascular deaths. Compared to the reference quartile, the multivariate-adjusted hazard ratios and 95% confidence intervals for all-cause mortality were 1.02 (1.01-1.05; p = 0.008) in the fourth quartile. Dose-response analysis revealed a non-linear association. However, no significant associations were found between the TyG index and cardiovascular mortality., Conclusions: The TyG index exhibited a non-linear association with the risk of all-cause mortality in diabetic patients., Competing Interests: Declaration of competing interest All authors have nothing to disclose regarding conflict of interest with respect to this manuscript., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Due to the chelation of phosphorus in the soil, it becomes unavailable for plant growth and development. The mechanisms by which phosphorus-solubilizing bacteria activate immobilized phosphorus to promote the growth and development of woody plants, as well as the intrinsic molecular mechanisms, are not clear. Through the analysis of microbial communities in the rhizosphere 16S V3-V4 and a homologous gene encoding microbial alkaline phosphomonoesterase (phoD) in phosphate-efficient (PE) and phosphate-inefficient apple rootstocks, it was found that PE significantly enriched beneficial rhizobacteria. The best phosphorus-solubilizing bacteria, Bacillus sp. strain 7DB1 (B2), was isolated, purified, and identified from the rhizosphere soil of PE rootstocks. Incubating with Bacillus B2 into the rhizosphere of apple rootstocks significantly increased the soluble phosphorus and flavonoid content in the rhizosphere soil. Simultaneously, this process stimulates the root development of the rootstocks and enhances plant phosphorus uptake. After root transcriptome sequencing, candidate transcription factor MhMYB15, responsive to Bacillus B2, was identified through heatmap and co-expression network analysis. Yeast one-hybrid, electrophoretic mobility shift assay, and LUC assay confirmed that MhMYB15 can directly bind to the promoter regions of downstream functional genes, including chalcone synthase MhCHS2 and phosphate transporter MhPHT1;15. Transgenic experiments with MhMYB15 revealed that RNAi-MhMYB15 silenced lines failed to induce an increase in flavonoid content and phosphorus levels in the roots under the treatment of Bacillus B2, and plant growth was slower than the control. In conclusion, MhMYB15 actively responds to Bacillus B2, regulating the accumulation of flavonoids and the uptake of phosphorus, thereby influencing plant growth and development., (© 2024 Society for Experimental Biology and John Wiley & Sons Ltd.)

Micro/nanoplastics (MNPs), as emerging pollutants, have been detected in both the maternal and fetal sides of the placenta in pregnant women, and their reproductive toxicity has been demonstrated in in vivo and in vitro experimental models. The Targeted Risk Assessment of Environmental Chemicals (TRAEC) strategy has been innovatively devised to facilitate valid risk assessment, encompassing a comprehensive evaluation of reliability, correlation, outcome fitness, and integrity across four dimensions based on the included published evidence and our own findings. This study serves as an application case of TRAEC, with 40 items of research evidence on the toxicity of MNPs to the placenta, which were rigorously screened and incorporated into the final scoring system. The final score for this TRAEC case study is 5.63, suggesting a moderate-to-low risk of reproductive toxicity associated with MNPs in the placenta, which may potentially increase with decreasing particle size. It is essential to emphasize that the findings also report original data from assays indicating that exposure to high-dose groups (100 μg/mL, 200 μg/mL) of 50 nm and 200 nm polystyrene nanoplastics (PS-NPs) induces HTR8/SVneo cell cycle arrest and cell apoptosis, which lead to reproductive toxicity in the placenta by disrupting mitochondrial function. Overall, this study employed the TRAEC strategy to provide comprehensive insight into the potential reproductive health effects of ubiquitous MNPs.

Purpose: This study aims to investigate patient characteristics with lens zonular ligament abnormalities in Acute Primary Angle Closure (APAC), identifying related risk factors, and evaluating the efficacy of Pilocarpine, a miotic agent., Design: Retrospective case-control study., Methods: Conducted as a retrospective case-control study at Hebei Provincial Eye Hospital from January 1, 2019, to December 31, 2021, the study included APAC cases undergoing ultrasound phacoemulsification with or without glaucoma surgery. Zonular ligament status was determined by intraoperative indicators such as lens equator visibility post-mydriasis and anterior capsule wrinkling during capsulorhexis. Patients were categorized into APAC and APAC with Lens Subluxation (APACLS) groups. Demographic details, Central Anterior Chamber Depth (ACD), Axial Length (AL), ACD difference between eyes (ACDD), Lens Thickness (LT), Lens Position (LP), and Relative Lens Position (RLP) were recorded and compared. Pilocarpine's impact on intraocular pressure reduction was assessed. Statistical analysis involved bilateral t-tests (for normally distributed data comparing both eyes in each group), non-parametric tests (for comparing two groups with non-normally distributed data), binary logistic regression, and Receiver Operating Characteristic (ROC) curve analysis for cutoff value determination related to zonular abnormalities., Results: The APAC and APACLS groups showed no significant difference in age of onset (70.11 ± 8.67 years vs. 70.11 ± 8.67 years, P = 0.159) or axial length of the eye (22.35 ± 0.64 mm vs. 22.36 ± 0.78 mm, P = 0.929). In the APACLS group, LT was greater (5.24 ± 0.37 mm vs. 5.01 ± 0.36 mm, P = 0.011), ACD was shallower (1.42 ± 0.24 mm vs. 1.69 ± 0.24 mm, P = 0.000), and ACDD was larger (0.38 ± 0.22 mm vs. 0.18 ± 0.18 mm, P = 0.000). The LP was lower (4.04 ± 0.32 vs. 4.20 ± 0.22, P = 0.013), and RLP was also lower (0.18 ± 0.02 vs. 0.19 ± 0.01, P = 0.015) in the APACLS group. A shallow ACD and a large ACDD were identified as risk factors associated with lens zonular abnormalities in the affected eyes (ACD OR value 63.97, P = 0.027; ACDD OR value 0.029, P = 0.027). Using ROC curve analysis, the cutoff value for ACDD was determined to be 0.375 mm, and for ACD, it was 1.6 mm. After pupil constriction with Pilocarpine eye drops, the proportion of patients whose intraocular pressure normalized was 75.36 % (52/69) in the APAC group and 71.43 % (25/35) in the APACLS group., Conclusion: ACD and ACDD in the affected eye are indicative of increased risk for APACLS. An ACD <1.6 mm and ACDD >0.375 mm should prompt consideration of zonular ligament abnormalities. Pilocarpine as a miotic treatment is safe and effective for such patients., Competing Interests: None declared., (© 2024 The Authors. Published by Elsevier Ltd.)

Knowledge distillation (KD), as an effective compression technology, is used to reduce the resource consumption of graph neural networks (GNNs) and facilitate their deployment on resource-constrained devices. Numerous studies exist on GNN distillation, and however, the impacts of knowledge complexity and differences in learning behavior between teachers and students on distillation efficiency remain underexplored. We propose a KD method for fine-grained learning behavior (FLB), comprising two main components: feature knowledge decoupling (FKD) and teacher learning behavior guidance (TLBG). Specifically, FKD decouples the intermediate-layer features of the student network into two types: teacher-related features (TRFs) and downstream features (DFs), enhancing knowledge comprehension and learning efficiency by guiding the student to simultaneously focus on these features. TLBG maps the teacher model's learning behaviors to provide reliable guidance for correcting deviations in student learning. Extensive experiments across eight datasets and 12 baseline frameworks demonstrate that FLB significantly enhances the performance and robustness of student GNNs within the original framework.

The side reactions and dendrite growth at the interface of Zn anodes greatly limit their practical applications in Zn metal batteries. Herein, we propose a hybrid molecular sieve-based interfacial layer (denoted as Z 7 M 3 ) with a hierarchical porous structure for Zn metal anodes, which contains 70 vol % microporous ZSM-5 molecular sieves and 30 vol % mesoporous MCM-41 molecular sieves. Through comprehensive molecular dynamics simulations, we demonstrate that the mesopores (∼2.5 nm) of MCM-41 can limit the disordered diffusion of free water molecules and increase the wettability of the interfacial layer toward aqueous electrolytes. In addition, the micropores (∼0.56 nm) of ZSM-5 can optimize the Zn 2+ solvation structures by reducing the bonded water molecules, which simultaneously decrease the constraint force of solvated water molecules to Zn 2+ ions, thus promoting the penetrability and diffusion kinetics of Zn 2+ ions in Z 7 M 3 . The synergetic effects from the hybrid molecular sieves maintain a constant Zn 2+ concentration on the surface of the Zn electrode during Zn deposition, contributing to dendrite-free Zn anodes. Consequently, Z 7 M 3 -coated Zn electrodes achieved excellent cycling stability in both half and full cells.

Hybrid systems combined eletrocatalysis and Fenton-like process attract a lot of attention due their outstanding performance and unique mechanism. Here, we proposed an efficient, cost-effective, and versatile electrochemical activation (ECA) system for efficient water purification, and intensively studied the synergistic effects between electrocatalysis and peroxymonosulfate (PMS)-based advanced oxidation. The ECA system achieved complete removal of 20 ppm tetracycline hydrochloride (TCH) in 15 min, with a rate constant of 0.338 min -1 . Its performance was assessed across various operational parameters (PMS dosage, pH, applied voltage, electrode interval, temperature, co-existed ions, biomass, different oxidants), demonstrating its broad applicability and stability. Excellent degradation and mineralization for other 12 kinds of refractory organic pollutants were also achieved. The outstanding performance can be attributed to the synergistic effect in the system, in which electrocatalytic reduction of dissolved oxygen generated H 2 O 2 and O 2 •- , boosting the number of reactive species, such as 1 O 2 , by interacting with PMS. Furthermore, the presence of organic matter promotes electron transfer, amplifying the system's degradation capability. These findings not only highlight the ECA system's effectiveness in organic pollutant removal but also offer insights into the underlying degradation mechanisms, paving the way for future advancements in water purification technologies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Initial investigative research indicated that the essential oil from Chimonanthus nitens Oliv. Leaves (CLO) significantly reduces lung tissues inflammation and effectively repairs Acute lung injury (ALI) mice model. However, the mechanism underlying is not clear, and the impacts of CLO on oxidative stress require further investigation., Aim of the Study: The purpose of the experiment was to validate the influence of CLO in ALI model mice, as well as its potential mechanisms., Materials and Methods: Lipopolysaccharide-induced establishment of the A549 cell inflammation model, and ALI mice model was established by intrathecal administration of LPS., Results: CLO significantly reduced the release of inflammatory cytokines in A549 cells, lowered MDA and ROS levels, and enhanced SOD activity. Animal experiment results showed that CLO dramatically decreased white blood cell count, the expression of inflammatory cytokines, and the destruction of alveolar structures. CLO enhances the activity of antioxidant enzymes. Western Blot and q-PCR analyses have revealed that the mechanism of CLO is correlation with the NF-κB and Nrf2 signaling pathways in cellular and animal models. Pathway inhibitor experiments indicated that there might be functional crosstalk between these two pathways., Conclusions: CLO may regulate inflammation and oxidative stress in LPS-induced ALI through NF-κB and Nrf2 signaling pathways. This finding could be novel in the pharmacological treatment of ALI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Infective endophthalmitis is an ophthalmic infection that in severe cases can cause complete loss of vision. In children, the defense against infection is low and eye tissue is not fully developed, leading to increased vulnerability to endophthalmitis. Children may be unable to understand the symptoms; thus, developing a method for prevention and treatment of this disease in children is important. Therefore, we analyzed the clinical and pathogenic characteristics of infectious endophthalmitis in children and provided evidence for clinical treatment. The clinical data of 78 children (78 eyes) with infectious endophthalmitis were retrospectively analyzed. The clinical characteristics, pathogen distribution, drug sensitivity, clinical medication, and treatments were summarized and analyzed. In total, 74 (94.87%) had ocular infections caused by trauma and 75 (96.15%) were from rural townships. A total of 108 sterile specimens were examined, with a positive detection rate of 37.04%. The sensitivity rates of Gram-positive cocci and bacilli to vancomycin were 100%. The sensitivity rates of Gram-negative bacilli to ceftazidime, piperacillin/tazobactam, amikacin, gentamicin, ciprofloxacin, and levofloxacin were 100%. Of the 78 patients, 53 (67.95%) received intravitreal injection and 54 (69.23%) underwent vitrectomy. Trauma is the main factor leading to infectious endophthalmitis in children, wherein Gram-positive bacteria are the most common pathogens. Thus, a timely understanding of the pathogen and drug sensitivity is needed. Intravitreal injection and vitrectomy are effective treatments., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Development of low temperature catalytic pyrolysis technology for heated tobacco sheets is expected to increase the aroma of heated tobacco products and improve their overall smoking quality. In this study, the low temperature pyrolysis performances of heated tobacco sheets catalyzed by various anionic sodium salts were investigated using TG-DTG, Py-GC-MS technology and smoke routine chemical composition analysis. The results showed that the total weight loss between 100°C and 300°C increased by 7.8%-13.15% after adding various anionic sodium salts, among which, sodium acetate and sodium tartrate showed a relatively higher weight loss. The relative content of free hydroxyacetone, furfuryl alcohol, butyrolactone and megastigmatrienone in the pyrolysis gas increased, while the relative content of free nicotine decreased. With the change of anionic species, the catalytic decomposition ability of cellulose, lignin, and other substances may change, resulting in the distribution alteration of compounds in the pyrolysis gas. After adding sodium acetate and sodium citrate, the release of total particulate matter (TPM), glycerol, and nicotine in flue gas increased. Overall, the addition of sodium acetate and sodium citrate showed a higher low temperature pyrolysis performance of heated tobacco sheets. The research results in this paper provide data support for changing the low temperature catalytic pyrolysis performance of heated tobacco sheets by adjusting the type of anions in sodium salts., Competing Interests: Authors XZ, QW, DA, HT, ZZ, KC, YW, WQ, BoL, YN, and BiL were employed by China Tobacco Henan Industrial Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhao, Wang, Ai, Tian, Zhang, Cao, Wang, Qi, Li, Niu, Meng, Gao and Li.)

This study addresses the energy-intensive nature of conventional wastewater treatment processes and proposes a solution through the development of a green, low-energy, and multifunctional wastewater treatment technology. The research focuses on a multifunctional self-driven photoelectrocatalytic (PEC) system, exploring its four-in-one applications in eliminating organic pollutants, reducing U(VI), generating electrical energy, and disinfecting pathogenic microorganisms. A TiO 2 -decorated carbon felt (CF@TiO 2 ) cathode is synthesized to enhance interfacial charge transfer, with TiO 2 coating improving surface binding sites (edge TiO and adsorbed -OH) for UO 2 2+ adsorption and reduction. The self-driven PEC system, illuminated solely with simulated sunlight, exhibits remarkable efficiency in removing nearly 100 % of uranium within 0.5 h and simultaneously degrading 99.9 % of sulfamethoxazole (SMX) within 1.5 h, all while generating a maximum power output density (P max ) of approximately 1065 μW·cm -2 . The system demonstrates significant anti-interference properties across a wide pH range and coexisting ions. Moreover, 49.4 % of the fixed uranium on the cathode is reduced into U(IV) species, limiting its migration. The self-driven PEC system also excels in detoxifying various toxic organic compounds, including tetracycline, chlortetracycline, and oxytetracycline, and exhibits exceptional sterilization ability by disinfecting nearly 100 % of Escherichia coli within 0.5 h. This work presents an energy-saving, sustainable, and easily recyclable wastewater purification system with four-in-one capabilities, relying solely on sunlight for operation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Thin polysilicon (poly-Si)-based passivating contacts can reduce parasitic absorption and the cost of n-TOPCon solar cells. Herein, n + -poly-Si layers with thicknesses of 30~100 nm were fabricated by low-pressure chemical vapor deposition (LPCVD) to create passivating contacts. We investigated the effect of n + -poly-Si layer thickness on the microstructure of the metallization contact formation, passivation, and electronic performance of n-TOPCon solar cells. The thickness of the poly-Si layer significantly affected the passivation of metallization-induced recombination under the metal contact ( J 0, metal ) and the contact resistivity ( ρ c ) of the cells. However, it had a minimal impact on the short-circuit current density ( J sc ), which was primarily associated with corroded silver (Ag) at depths of the n + -poly-Si layer exceeding 40 nm. We introduced a thin n + -poly-Si layer with a thickness of 70 nm and a surface concentration of 5 × 10 20 atoms/cm 3 . This layer can meet the requirements for low J 0, metal and ρ c values, leading to an increase in conversion efficiency of 25.65%. This optimized process of depositing a phosphorus-doped poly-Si layer can be commercially applied in photovoltaics to reduce processing times and lower costs.

Ischemic stroke (IS) remains a serious threat to human health. Neuroinflammatory response is an important pathophysiological process after IS. Circular RNAs (circRNAs), a member of the non-coding RNA family, are highly expressed in the central nervous system and widely involved in regulating physiological and pathophysiological processes. This study reviews the current evidence on neuroinflammatory responses, the role of circRNAs in IS and their potential mechanisms in regulating inflammatory cells, and inflammatory factors affecting IS damage. This review lays a foundation for future clinical application of circRNAs as novel biomarkers and therapeutic targets., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

Heteroions doped Ag 2 S nanocrystals (NCs) exhibiting enhanced near-infrared-II emission (NIR-II) hold great promise for glioma diagnosis. Nevertheless, current doped Ag 2 S NCs paradoxically improved properties via toxic dopants, and the blood-brain barrier (BBB) constitutes another challenge for orthotopic glioma imaging. Thus, it is urgent to develop biofriendly high-bright Ag 2 S NCs with active BBB-penetration for glioma-targeted imaging. Herein, bismuth (Bi) was screened to obtain Bi-Ag 2 S NCs with high absolute PLQY (∼13.3%) for its matched ionic-radius (1.03 Å) with Ag + . The Bi-Ag 2 S NCs exhibited a higher luminance and deeper penetration (5-6 mm) than clinical indocyanine green. Upon conjugation with lactoferrin, the NCs acquired BBB-crossing and glioma-targeting abilities. Time-dependent NIR-II-imaging demonstrated their effective accumulation in glioma with skull/scalp intact after intravenous injection. Moreover, the toxic-metal-free NCs exhibited negligible toxicity and great biocompatibility. The success of leveraging the ion-radii comparison may unlock the full potential of doped-Ag 2 S NCs in bioimaging and inspire the development of various doped NIR-II NCs.

The EP300-ZNF384 fusion gene is an oncogenic driver in B-cell acute lymphoblastic leukemia (B-ALL). In the present study, we demonstrated that EP300-ZNF384 substantially induces the transcription of IL3RA and the expression of IL3Rα (CD123) on B-ALL cell membranes. Interleukin 3 (IL-3) supplementation promotes the proliferation of EP300-ZNF348-positive B-ALL cells by activating STAT5. Conditional knockdown of IL3RA in EP300-ZF384-positive cells inhibited the proliferation in vitro, and induced a significant increase in overall survival of mice, which is attributed to impaired propagation ability of leukemia cells. Mechanistically, the EP300-ZNF384 fusion protein transactivates the promoter activity of IL3RA by binding to an A-rich sequence localized at -222/-234 of IL3RA. Furthermore, forced EP300-ZNF384 expression induces the expression of IL3Rα on cell membranes and the secretion of IL-3 in CD19-positive B precursor cells derived from healthy individuals. Doxorubicin displayed a selective killing of EP300-ZNF384-positive B-ALL cells in vitro and in vivo. Collectively, we identify IL3RA as a direct downstream target of EP300-ZNF384, suggesting CD123 is a potent biomarker for EP300-ZNF384-driven B-ALL. Targeting CD123 may be a novel therapeutic approach to EP300-ZNF384-positive patients, alternative or, more likely, complementary to standard chemotherapy regimen in clinical setting., (© 2024. The Author(s).)

The emerging stress caused by nanomaterials in the environment is of great concern because they can have toxic effects on organisms. However, thorough study of the interactions between cells and diverse nanoparticles (NPs) using a unified approach is challenging. Here, we present a novel approach combining stimulated emission depletion (STED) microscopy and scanning transmission electron microscopy (STEM) for quantitative assessment, real-time tracking, and in situ imaging of the intracellular behavior of gold-silver nanoclusters (AuAgNCs), based on their fluorescence and electron properties. The results revealed an aggregated state of AuAgNCs within the mitochondria and an increase in sulfur content in AuAgNCs, presumably owing to their reaction with thiol-containing molecules inside the mitochondria. Moreover, AuAgNCs (100 μg/mL) induced a 75% decline in mitochondrial membrane potential and a 12-fold increase of mitochondrial reactive oxygen species in comparison to control. This mitochondrial damage may be triggered by the reaction of AuAgNCs with thiol, which provides direct imaging evidence for uncovering the action mechanism of AuAgNCs on the mitochondria. The proposed dual-imaging strategy using STED and STEM is a potential tool to offer valuable insights into cytotoxicity between subcellular structures and diverse NPs, and can serve as a key strategy for nanomaterial biosafety assessment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

For the aroma enhancement research of heated cigarettes, it is worth exploring whether tobacco can be pyrolyzed into pyrolysis liquids containing a large number of volatile aroma components. In this study, tobacco pyrolysis liquids were prepared in subcritical/supercritical ethanol, and their applications in the aroma enhancement of heated cigarettes were investigated. The optimal conditions of supercritical liquefaction reactions were determined by optimizing the reaction time, liquid/solid mass ratio and temperature conditions. Moreover, the effect of supercritical liquefaction conditions on volatile aroma components in tobacco pyrolysis liquids was investigated by GC-MS. The results indicated that the reaction temperature had the most significant impact on the tobacco pyrolysis reaction, and higher reaction temperature promoted the pyrolysis conversion of tobacco, resulting in enhanced tobacco conversion and a high content of volatile components in the tobacco pyrolysis liquid. The optimal reaction conditions for the preparation of tobacco pyrolysis liquid were found to be a temperature of 220°C, a liquid/solid mass ratio = 15, and a 2-h reaction time. Meanwhile, the content of ester compounds and nicotine in the tobacco pyrolysis liquid increased significantly with the increase of reaction temperature. Sub/supercritical ethanol treatment significantly destroyed the surface structure of tobacco, and the degree of tobacco depolymerization increased when temperature rised. The analysis of aroma compounds in the smoke of heated cigarettes indicated that the tobacco pyrolysis liquid could significantly increase the release of aromatic substances and has a significant aroma-enhancing effect. This article proposed and prepared tobacco pyrolysis liquid in subcritical/supercritical ethanol and explored its potential application in the aroma enhancement of heated cigarettes, offering a new route for flavor enhancement technology for this type of product., Competing Interests: Authors XZ, SZ, YX, HX, ZZ, HT, and SM were employed by China Tobacco Henan Industrial Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhao, Zhao, Xu, Xu, Zhang, Tian, He, Ma, Gao and Ma.)

Objective: Hydroxychloroquine (HCQ) is an essential drug in the treatment of systemic lupus erythematosus (SLE). This study aimed to detect the concentrations of HCQ and its metabolites from peripheral blood of SLE patients and to investigate the relationship between those concentrations and SLE disease activity., Methods: 176 SLE patients treated with HCQ were enrolled in this study. The concentrations of HCQ and its metabolites in their peripheral blood were measured by high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Patients' disease activity was evaluated with the systemic lupus erythematosus disease activity index (SLEDAI). The variables between different concentrations or treatments were statistically analyzed. Linear regression was employed to explore relationships between the concentrations of HCQ and its metabolites with the disease activity., Results: The SLEDAI was lower in patients with higher concentrations of HCQ, desethylhydroxychloroquine (DHCQ), and desethylchloroquine (DCQ) (P = 0.024, P = 0.018, and P = 0.003, respectively). There were no significant differences in SLEDAI and the concentrations of HCQ and its metabolites among groups with different treatments (P > 0.05). After adjusting age, gender, disease duration, HCQ dose adjusted to actual body weight, and glucocorticoid (GC) dose, the SLEDAI was negatively correlated with the concentrations of HCQ, DHCQ, DCQ and bisdesethylchloroquine (BDCQ) (P = 0.007, P = 0.011, P = 0.029, and P = 0.008, respectively). After grouping analysis, in patients treated with HCQ and GC, the SLEDAI was negatively correlated with concentrations of HCQ, DHCQ and BDCQ (P = 0.011, P = 0.035, and P = 0.036, respectively)., Conclusions: The concentrations of HCQ and metabolites were correlated with the SLE disease activity after adjusting possible confounding factors, indicating that HCQ and its metabolites might play certain immunoregulatory roles in SLE treatment. Moreover, GC might have a synergistic effect with HCQ. It is helpful in clinical management and follow-up to monitor the concentrations of HCQ and its metabolites in SLE patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

We aimed to explore the role of immune and inflammatory indicators in cognitive dysfunction and disease severity in patients with Parkinson's disease (PD). A total of 123 patients with Parkinson's disease were enrolled in the PD group and 49 healthy volunteers in the control group. The patients with PD were further divided into 2 subgroups by evaluating cognitive function using the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE): the normal cognitive function (PD-NCI) group and the mild cognitive impairment (PD-MCI) group. Moreover, the PD patients were also divided into 2 subgroups using the defined scale of the Hoehn and Yahr (H-Y) stage: the early-stage group and the middle- and late-stage group. Immune and inflammatory indicators, including serum Aβ 1-42 , Tau, CD4 + , CD8 + , CD3 + , B lymphocytes cell, NK cell, Th17 cell, Treg cell, IL-6, IL-17, and TNF-α levels, were evaluated and analyzed to explore the potential correlation with the cognitive dysfunction and disease severity of PD. Among the 123 PD patients, 60 (48.8%) were diagnosed with mild cognitive impairment. Aβ 1-42 , CD4 + , CD8 + , CD3 + , and Treg levels observed in the PD-NCI group were lower than the control group (P < 0.001), while higher than the PD-MCI group (P < 0.001). The levels of Tau, Th17, IL-6, IL-17, and TNF-α observed in the PD-NCI group were higher than the control group (P < 0.001), while lower than in the PD-MCI group (P < 0.01). Using the same method, the results of the early-stage group and the middle- and the late-stage group were the same as above. Logistic regression analysis and ROC curve estimation were performed and indicated that the variation of Tau, CD8 + , Treg, TNF-α levels was associated with cognitive decline in PD patients, and may serve as markers of PD onset. Furthermore, the variation of Aβ 1-42 , IL-6, and TNF-α levels was found to correlate with the disease severity of PD. The immune and inflammatory-related indicators may represent an important factor in the pathogenesis of PD, cognitive dysfunction, and disease severity. The variation of Tau protein, CD8 + , Treg, and TNF-α levels are associated with the cognitive dysfunction of PD, which may be considered as onset markers. Moreover, the variation of Aβ 1-42 , IL-6, and TNF-α levels can predict the progression of PD., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Coronary microvascular disease (CMVD) is associated with adverse cardiovascular outcomes. However, there is no reliable and noninvasive quantitative diagnostic method available for CMVD. The use of a pressure wire to measure the index of microcirculatory resistance (IMR) is possible, but it has inevitable practical restrictions. We hypothesized that computation of the quantitative flow ratio could be used to predict CMVD with symptoms of ischemia and no obstructive coronary artery disease (INOCA)., Methods: We retrospectively assessed the diagnostic efficiency of the quantitative flow ratio-derived index of microcirculatory resistance (QMR) in 103 vessels from 66 patients and compared it with invasive IMR using the thermodilution technique., Results: Patients were divided into the CMVD group (41/66, 62.1%) and non-CMVD group (25/66, 37.9%). Pressure wire IMR measurements were made in 103 coronary vessels, including 44 left descending arteries, 18 left circumflex arteries, and 41 right coronary arteries. ROC curve analysis showed a good diagnostic performance of QMR for all arteries (area under the curve = 0.820, 95% confidence interval 0.736-0.904, p &lt; 0.001) in predicting microcirculatory function. The optimal cut-off for QMR to predict microcirculatory function was 266 (sensitivity: 82.9%, specificity: 72.6%, and diagnostic accuracy: 76.7%)., Conclusion: QMR is a promising tool for the assessment of coronary microcirculation. The assessment of the IMR without the use of a pressure wire may enable more rapid, convenient, and cost-effective assessment of coronary microvascular function., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Highly proliferative and metastatic tumors are constantly exposed to both intrinsic and extrinsic factors that induce adaptation to stressful conditions. Chronic adaptation to endoplasmic reticulum (ER) ER stress is common to many different types of cancers, and poses a major challenge for acquired drug resistance. Here we report that LAMC2, an extracellular matrix protein upregulated in many types of cancers, is localized in the ER of lung, breast, and liver cancer cells. Under tunicamycin-induced ER stress, protein level of LAMC2 is upregulated. Transfection of cancer cells with LAMC2 resulted in the attenuation of ER stress phenotype, accompanied by elevation in mitochondrial membrane potential as well as reduction in reactive oxygen species (ROS) levels and apoptosis. In addition, LAMC2 forms protein complexes with MYH9 and MYH10 to promote mitochondrial aggregation and increased ER-mitochondria interaction at the perinuclear region. Moreover, overexpression of LAMC2 counteracts the effects of ER stress and promotes tumor growth in vivo. Taken together, our results revealed that in complex with MYH9 and MYH10, LAMC2 is essential for promoting ER-mitochondria interaction to alleviate ER stress and allow cancer cells to adapt and proliferate under stressful conditions. This study provides new insights and highlights the promising potential of LAMC2 as a therapeutic target for cancer treatment., (© 2023. The Author(s).)

Although great progress has been made in the diagnosis and treatment of acute myocardial infarction (AMI) in recent years, its morbidity and mortality are still relatively high. In this study, we explain that the function of Sestrin2 gene in Anxiety and Depression Myocardial infarction and its possible mechanism. 26 patients with Anxiety and Depression Myocardial infarction (ADMI) and 26 normal volunteers were collected from our hospital. All mice anaesthetized using 50 mg/kg of pentobarbital sodium and the left anterior descending arteries (LAD) were ligated to induce myocardial infarction. H9c2 cells were stimulated with 5% oxygen (O2) and 5% carbon dioxide (CO2) and 90% N2 for 24 h. The serum expression of Sestrin2 in patients with ADMI was up-regulated. Sestrin2 gene up-regulation reduced collagen I/II and KEAP1 mRNA expressions, and increased GPX4 and Nrf2 mRNA expressions in vitro model of AMI. Down-regulation of Sestrin2 increased collagen I/II and KEAP1 mRNA expressions, and decreased GPX4 and Nrf2 mRNA expressions in vitro model of AMI. These data confirmed that Sestrin2 reduced inflammation and ferroptosis in model of ADMI by LKB1-mediated AMPK activation. This infers that Sestrin2 is potential target to be used in the treatment of premature AMI.

There is an argument that BPA substitutes may have the same or more deleterious health effects as BPA due to their structural similarity. This study explored the association between urinary BPA substitutes and precocious puberty among girls by including 120 girls with precocious puberty (cases) aged 2-10 years enrolled at Nanjing Children's Hospital Department of Endocrinology in China between April 2021 to September 2021 and 145 healthy girls (controls) recruited from a primary school. Logistic regression was used to evaluate the effect of single exposures, and Bayesian kernel machine regression (BKMR) and quantile-based g-computation were used for the mixed effect. In the multivariate logistic regression, BPS (bisphenol S), TBBPA (tetrabromobisphenol A), and BPFL (bisphenol-FL) were significantly associated with increased risk of precocious puberty (odds ratio (OR) = 1.75, 95% confidence interval (CI): 1.13, 2.76, p = 0.014), (OR = 1.46, CI: 1.06, 2.05; p = 0.023), and (OR = 1.47, CI: 1.01, 2.18; p = 0.047), respectively. The BMKR and quantile-based g-computation models revealed consistent associations for single exposures and there was insufficient evidence for the associations of the mixed exposure of bisphenols with precocious puberty. In conclusion, BPA substitutes such as BPS, TBBPA, and BPFL may be associated with an increased risk of precocious puberty in girls.

Electrocatalytic reduction of CO 2 to valuable chemicals can alleviate the energy crisis, and solve the greenhouse effect. The key is to develop non-noble metal electrocatalysts with high activity, selectivity, and stability. Herein, bimetallic metal organic frameworks (MOFs) materials (BiZn-MOF, BiSn-MOF, and BiIn-MOF) were constructed by coordinating the metals Zn, In, Sn, and Bi with the organic ligand 3-amino-1H-1,2,4-triazole-5-carboxylic acid (H 2 atzc) through a rapid microwave synthesis approach. The coordination centers in bimetallic MOF catalyst were regulated to optimize the catalytic performance for electrochemical CO 2 reduction reaction (CO 2 RR). The optimized catalyst BiZn-MOF exhibited higher catalytic activity than those of Bi-MOF, BiSn-MOF, and BiIn-MOF. BiZn-MOF exhibited a higher selectivity for formate production with a Faradic efficiency (FE = 92%) at a potential of -0.9 V (vs. RHE, reversible hydrogen electrode) with a current density of 13 mA cm -2 . The current density maintained continuous electrolysis for 13 h. The electrochemical conversion of CO 2 to formate mainly follows the *OCHO pathway. The good catalytic performance of BiZn-MOF may be attributed to the Bi-Zn bimetallic coordination centers in the MOF, which can reduce the binding energies of the reaction intermediates by tuning the electronic structure and atomic arrangement. This study provides a feasible strategy for performance optimization of bismuth-based catalysts.

Background: The correlation between percutaneous coronary intervention (PCI)-related microvascular dysfunction (MVD) and plaque characteristics remains unclear. To investigate this correlation and its prognosis, we assessed changes in MVD by angiographic microvascular resistance (AMR) and intracoronary ultrasound scans after PCI., Methods: We conducted a retrospective study that enrolled 250 patients with coronary artery disease between July 2016 and December 2018. We collected demographic characteristics, laboratory tests, coronary angiography (CAG) and intracoronary ultrasound findings. We calculated quantitative flow ratio (QFR) and AMR by CAG. The endpoint was vessel-oriented composite outcomes (VOCOs)., Results: After 47 exclusions, we divided 203 cases into a deteriorated group (n=139) and an improved group (n=64) based on AMR change after PCI. Compared with the improved group, the deteriorated group had smaller lumen area [3.03 (interquartile range, 2.20-3.91) vs . 3.55 mm 2 (interquartile range, 2.45-4.57), P=0.033], higher plaque burden [78.92% (interquartile range, 73.95-82.61%) vs . 71.93% (interquartile range, 62.70-77.51%), P<0.001], and higher proportion of lipidic components (13.86%±4.67% vs . 11.78%±4.41%, P=0.024). Of 186 patients who completed 4.81±1.55 years follow-up, 56 developed VOCOs. Receiver-operating characteristic (ROC) curve analysis showed post-PCI AMR and VOCOs correlation (area under the curve: 0.729, P<0.001). Multivariate regression analysis showed post-PCI AMR >285 mmHg·s/m correlated with adverse outcome (hazard ratio =4.350; 95% confidence interval: 1.95-9.703; P<0.001)., Conclusions: Intravascular ultrasound (IVUS) imaging and AMR revealed an association of post-PCI MVD with a smaller lumen area, more severe plaque burden, and a higher percentage of lipidic components. Post-PCI MVD was an independent risk factor for poor prognosis., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-414/coif). JX received grants from the Hangzhou Agricultural and Social Development Scientific Research Project (No. 20220919Y066). JH received grants from Funds for International Cooperation and Exchange of the National Natural Science Foundation of China (No. 62161160312) and Zhejiang Provincial Key Research and Development Program (No. 2020C03018). The other authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Objective: To explore the correlation of mitochondrial DNA (mtDNA) variants and coronary heart disease (CHD) in a Chinese pedigree and the possible molecular mechanisms., Methods: A Chinese pedigree featuring matrilineal inheritance of CHD who visited Hangzhou First People's Hospital in May 2022 was selected as the study subject. Clinical data of the proband and her affected relatives was collected. By sequencing the mtDNA of the proband and her pedigree members, candidate variants were identified through comparison with wild type mitochondrial genes. Conservative analysis among various species was conducted, and bioinformatics software was used to predict the impact of variants on the secondary structure of tRNA. Real-time PCR was carried out to determine the copy number of mtDNA, and a transmitochondrial cell line was established for analyzing the mitochondrial functions, including membrane potential and ATP level., Results: This pedigree had contained thirty-two members from four generations. Among ten maternal members, four had CHD, which yielded a penetrance rate of 40%. Sequence analysis of proband and her matrilineal relatives revealed the presence of a novel m.4420A>T variant and a m.10463T>C variant, both of which were highly conserved among various species. Structurally, the m.4420A>T variant had occurred at position 22 in the D-arm of tRNAMet, which disrupted the 13T-22A base-pairing, while the m.10463T>C variant was located at position 67 in the acceptor arm of tRNAArg, a position critical for steady-state level of the tRNA. Functional analysis revealed that patients with the m.4420A>T and m.10463T>C variants exhibited much fewer copy number of mtDNA and lower mitochondrial membrane potential (MMP) and ATP contents (P < 0.05), which were decreased by approximately 50.47%, 39.6% and 47.4%, respectively., Conclusion: Mitochondrial tRNAMet 4420A>T and tRNAArg 10463T>C variants may underlay the maternally transmitted CHD in this pedigree, which had shown variation in mtDNA homogeneity, age of onset, clinical phenotype and other differences, suggesting that nuclear genes, environmental factors and mitochondrial genetic background have certain influence on the pathogenesis of CHD.

Background: Anaplastic lymphoma kinase (ALK) overexpression and gene alterations have been detected in several mesenchymal tumors, with significant implications for diagnosis, therapy and prognosis. However, few studies have investigated the correlation between ALK expression status and clinicopathological characteristics in patients with gastrointestinal stromal tumors (GISTs)., Methods: A total of 506 GIST patients were enrolled. Sanger sequencing was employed to detect c-KIT and PDGFRA gene mutations. The tissue microarray (TMA) technique and immunohistochemistry were employed to identify the ALK (clone: 1A4 and D5F3) expression status in the tumor tissues. The ALK gene variants of IHC-positive cases were analyzed by fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS). The clinicopathological data were analyzed using SPSS Statistics 26.0., Results: Among the 506 GIST patients, the c-KIT mutation accounted for 84.2% (426/506), followed by PDGFRA mutation (10.3%, 52/506), while the wild-type accounted for the least (5.5%, 28/506). ALK-positive expression was detected in PDGFRA-mutant GISTs (7.7%, 4/52) but negative for c-KIT-mutant or wild-type GISTs by IHC. Four ALK IHC-positive patients were all male. The tumors all occurred outside the stomach. The predominant patterns of growth were epithelioid (2/4), spindle (1/4), and mixed type (1/4). They were all identified as high-risk classification according to the National Institutes of Health (NIH) classification. Aberrant ALK mutations were not identified by DNA-based NGS except in one of the 4 cases with amplification by FISH., Conclusion: Our study revealed 7.7% (4/52) of ALK expression in PDGFRA-mutant GISTs, indicating that molecular tests were required to rule out the possibility of PDGFRA-mutant GISTs when encountering ALK-positive mesenchymal tumors with CD117-negative or weakly positive in immunohistochemical staining., (© 2023. The Author(s).)

Background: It has previously been observed that the prognostic value of tumor size varied according to different stages patients enrolled in gastric cancer. We aimed to investigate the influence of T stage on the prognostic and predicting value of tumor size., Material and Methods: A total of 13,585 patients with stage I-III gastric cancer were selected from the Surveillance, Epidemiology, and End Results Program (SEER) database. Univariate and multivariate cox regression analysis stratified by T stage were performed. C-index and time-dependent receiver operating characteristic curve (ROC) curve were applied to assess discrimination ability of tumor size and other factors. Nomograms were constructed to further assess the performance of tumor size in a specific model. Calibration ability, discrimination ability, reclassification ability and clinical benefits were executed to judge the performance of models., Results: Stratified analyses according to T stage illustrated that with the increase of T stage, the effect of tumor size on overall survival (OS) and cancer-specific survival (CSS) significantly decreased. Moreover, tumor size showed superior discrimination ability in T1 gastric cancer, outperformed other prognostic factors in predicting both CSS (C-index: 0.666, AUC: 0.687) and OS (C-index: 0.635, AUC: 0.660). The cox regression model included tumor size showed better performance than the model excluded tumor size in every aspect., Conclusion: T stage had a negative impact on the predicting value of tumor size. Tumor size showed significant prognostic value in T1 gastric cancer, which may be effective in clinical practice., (© 2023. The Author(s).)

Background: Epicardial adipose tissue (EAT) is directly related to coronary artery disease (CAD), but little is known about its role in hemodynamically significant CAD. Therefore, our goal is to explore the impact of EAT volume on hemodynamically significant CAD., Methods: Patients who underwent coronary computed tomography angiography (CCTA) and received coronary angiography within 30 days were retrospectively included. Measurements of EAT volume and coronary artery calcium score (CACs) were performed on a semi-automatic software based on CCTA images, while quantitative flow ratio (QFR) was automatically calculated by the AngioPlus system according to coronary angiographic images., Results: This study included 277 patients, 112 of whom had hemodynamically significant CAD and showed higher EAT volume. In multivariate analysis, EAT volume was independently and positively correlated with hemodynamically significant CAD [per standard deviation (SD) cm 3 ; odds ratio (OR), 2.78; 95% confidence interval (CI), 1.86-4.15; P  < 0.001], but negatively associated with QFR min (per SD cm 3 ; β coefficient, -0.068; 95% CI, -0.109 to -0.027; P  = 0.001) after adjustment for traditional risk factors and CACs. Receiver operating characteristics curve analysis demonstrated a significant improvement in predictive value for hemodynamically significant CAD with the addition of EAT volume to obstructive CAD alone (area under the curve, 0.950 vs. 0.891; P  < 0.001)., Conclusion: In this study, we found that EAT volume correlated substantially and positively with the existence and severity of hemodynamically significant CAD in Chinese patients with known or suspected CAD, which was independent of traditional risk factors and CACs. In combination with obstructive CAD, EAT volume significantly improved diagnostic performance for hemodynamically significant CAD, suggesting that EAT could be a reliable noninvasive indicator of hemodynamically significant CAD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Jin, Gao, Zheng, Wu, Zhang, Zhu, Zhu, Xie, Wang, Tong and Huang.)

Background: The extensive usage of pesticides has led to a ubiquitous exposure in the Chinese general population. Previous studies have demonstrated developmental neurotoxicity associated with prenatal exposure to pesticides., Objectives: We aimed to delineate the landscape of internal pesticides exposure levels from pregnant women's blood serum samples, and to identify the specific pesticides associated with the domain-specific neuropsychological development., Methods: Participants included 710 mother-child pairs in a prospective cohort study initiated and maintained in Nanjing Maternity and Child Health Care Hospital. Maternal spot blood samples were collected at enrollment. Leveraging on an accurate, sensitive and reproducible analysis method for 88 pesticides, a total of 49 pesticides were measured simultaneously using gas chromatography-triple quadrupole tandem mass spectrometry (GC-MS/MS). After implementing a strict quality control (QC) management, 29 pesticides were reported. We assessed neuropsychological development in 12-month-old (n = 172) and 18-month-old (n = 138) children using the Ages and Stages Questionnaire (ASQ), Third Edition. Negative binomial regression models were used to investigate the associations between prenatal exposure to pesticides and ASQ domain-specific scores at age 12 and 18 months. Restricted cubic spline (RCS) analysis and generalized additive models (GAMs) were fitted to evaluate non-linear patterns. Longitudinal models with generalized estimating equations (GEE) were conducted to account for correlations among repeated observations. Weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were applied to examining the joint effect of the mixture of pesticides. Several sensitivity analyses were performed to assess the robustness of the results., Results: We observed that prenatal exposure to chlorpyrifos was significantly associated with a 4 % decrease in the ASQ communication scores both at age 12 months (RR, 0.96; 95 % CI, 0.94-0.98; P < 0.001) and 18 months (RR, 0.96; 95 % CI, 0.93-0.99; P < 0.01). In the ASQ gross motor domain, higher concentrations of mirex (RR, 0.96; 95 % CI, 0.94-0.99, P < 0.01 for 12-month-old children; RR, 0.98; 95 % CI, 0.97-1.00, P = 0.01 for 18-month-old children), and atrazine (RR, 0.97; 95 % CI, 0.95-0.99, P < 0.01 for 12-month-old children; RR, 0.99; 95 % CI, 0.97-1.00, P = 0.03 for 18-month-old children) were associated with decreased scores. In the ASQ fine motor domain, higher concentrations of mirex (RR, 0.98; 95 % CI, 0.96-1.00, P = 0.04 for 12-month-old children; RR, 0.98; 95 % CI, 0.96-0.99, P < 0.01 for 18-month-old children), atrazine (RR, 0.97; 95 % CI, 0.95-0.99, P < 0.001 for 12-month-old children; RR, 0.98; 95 % CI, 0.97-1.00, P = 0.01 for 18-month-old children), and dimethipin (RR, 0.94; 95 % CI, 0.89-1.00, P = 0.04 for 12-month-old children; RR, 0.93; 95 % CI, 0.88-0.98, P < 0.01 for 18-month-old children) were associated with decreased scores. The associations were not modified by child sex. There was no evidence of statistically significant nonlinear relationships between pesticides exposure and RRs of delayed neurodevelopment (P nonlinearity  > 0.05). Longitudinal analyses implicated the consistent findings., Conclusion: This study gave an integrated picture of pesticides exposure in Chinese pregnant women. We found significant inverse associations between prenatal exposure to chlorpyrifos, mirex, atrazine, dimethipin and the domain-specific neuropsychological development (i.e., communication, gross motor and fine motor) of children at 12 and 18 months of age. These findings identified specific pesticides with high risk of neurotoxicity, and highlighted the need for priority regulation of them., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Wide exposure to endocrine-disrupting chemicals (EDCs) poses a great risk on human health. However, few large-scale cohort studies have comprehensively estimated the association between EDCs exposure and mortality risk. This study aimed to investigate the association of urinary EDCs exposure with mortality risk and quantify attributable mortality and economic loss. Multivariable Cox proportional hazards regression models were performed to investigate the association of 38 representative EDCs exposure with mortality risk in the National Health and Nutrition Examination Survey (NHANES). During a median follow-up of 7.7 years, 47,279 individuals were enrolled. All-cause mortality was positively associated with 1-hydroxynaphthalene, 2-hydroxynaphthalene, cadmium, antimony, cobalt, and monobenzyl phthalate. Cancer mortality was positively associated with cadmium. Cardiovascular disease (CVD) mortality was positively associated with 1-hydroxynaphthalene, 2-hydroxynaphthalene, and 2-hydroxyfluorene. Nonlinear U-shaped relationships were found between all-cause mortality and cadmium and cobalt, which was also identified between 2-hydroxyfluorene and CVD mortality. J-shaped association of cadmium exposure with cancer mortality was also determined. EDCs exposure may cause 56.52% of total deaths (1,528,500 deaths) and around 1,897 billion USD in economic costs. Exposure to certain phthalates, polycyclic aromatic hydrocarbons, phytoestrogens, or toxic metals, even at substantially low levels, is significantly associated with mortality and induces high economic costs.

Nitrogen is critical for plant growth and development. With the increase of nitrogen fertilizer application, nitrogen use efficiency decreases, resulting in wasted resources. In apple (Malus domestica) rootstocks, the potential molecular mechanism for improving nitrogen uptake efficiency to alleviate low-nitrogen stress remains unclear. We utilized multi-omics approaches to investigate the mechanism of nitrogen uptake in two apple rootstocks with different responses to nitrogen stress, Malus hupehensis and Malus sieversii. Under low-nitrogen stress, Malus sieversii showed higher efficiency in nitrogen uptake. Multi-omics analysis revealed substantial differences in the expression of genes involved in flavonoid and lignin synthesis pathways between the two materials, which were related to the corresponding metabolites. We discovered that basic helix-loop-helix 130 (bHLH130) transcription factor was highly negatively associated with the flavonoid biosynthetic pathway. bHLH130 may directly bind to the chalcone synthase gene (CHS) promoter and inhibit its expression. Overexpressing CHS increased flavonoid accumulation and nitrogen uptake. Inhibiting bHLH130 increased flavonoid biosynthesis while decreasing lignin accumulation, thus improving nitrogen uptake efficiency. These findings revealed the molecular mechanism by which bHLH130 regulates flavonoid and lignin biosyntheses in apple rootstocks under low-nitrogen stress., Competing Interests: Conflict of interest statement. None declared., (© American Society of Plant Biologists 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous, EPA-designated priority pollutants for soil and groundwater, remaining recalcitrant to bioremediation because of limited bioavailability. In this work, we used naphthalene as a model PAH and soil bacteria Pseudomonas putida G7 to investigate the potential role of chemotaxis to enhance access to PAHs in heterogenous porous media. To this aim, we conducted transport experiments and numerical simulations with chemotactic bacteria and naphthalene trapped within a non-aqueous phase liquid (NAPL) mainly in low permeable areas of a dual-permeability microfluidic device. Microscopic imaging showed higher accumulations of chemotactic bacteria, about eight times that of nonchemotactic bacteria, at the junctures between high and low permeability regions. Pore-scale simulations for fluid flow and naphthalene revealed that the junctures are stagnant areas of fluid flow, which generated strong and temporally persistent naphthalene gradients. The landscape and densities of bacterial accumulation at the junctures were strongly regulated by flow profiles and naphthalene gradients especially those transverse to flow. We conducted macroscale simulations using convective dispersion equations with an added chemotactic velocity to account for directed migration toward naphthalene. Simulated results showed good consistency with experiments and pore-scale simulation as normalized bacterial accumulation per mm of NAPL was 7.80, 7.84 and 7.71 mm -1 for experiments, pore-scale and macroscale simulations, respectively. Macroscale simulations indicated that in the absence of grain-boundary restrictions associated with the pore structure bacterial dispersion needed to be increased by 50 % to account for the interplay between chemotactic response and naphthalene gradients at the pore-scale level. Our work details the mechanism of pore-scale chemotaxis in enhancing bioavailability of PAHs and its impact on biomass retention at the system level, which provides a potential solution toward more efficient bioremediation for contaminants such as PAHs with limited bioavailability., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

A cobalt (Co)-doped perovskite molybdenum trioxide (α-MoO 3 ) catalyst (Co-MO) was synthesized by a facile pyrolysis strategy and used for degrading various organic contaminants via peroxymonosulfate (PMS) activation. The doped Co was inserted in the inter space between the octahedron [MoO 6 ], facilitating the growth of the α-MoO 3 crystal on the [010] direction. This unique structure accelerated the activation of PMS as the Co-MO could function as a carrier for electron transfer to facilitate the Co(II)/Co(III) cycle in the Co-MO/PMS system. As a result, the Co-MO/PMS system showed noticeable activity for removing 100% bisphenol A (BPA) under a broad conditions within 30 min. The radical quenching test and electron paramagnetic resonance analysis revealed that singlet oxygen ( 1 O 2 ) was the main active species for BPA degradation in the Co-MO/PMS system, while free radicals, such as O 2 •- , SO 4 •- and •OH, were also produced as the intermediate species. Furthermore, the carrier mechanism may enable the Co-MO/PMS system maintain relatively high performance during repeat use, and also excellent adaptability was revealed by the well function in various water matrices and high activity in degrading various refractory organic pollutants. Our findings pave a useful avenue for the rational design of novel cobalt-doped catalysts with high catalytic performance toward wide environmental applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In concert with hijacking key genes to drive tumor progression, cancer cells also have the unique ability to dynamically interact with host microenvironment and discreetly manipulate the surrounding stroma, also known as the tumor microenvironment (TME), to provide optimal conditions for tumor cells to thrive and evade host immunity. Complex cellular crosstalk and molecular signaling between cancer cells, surrounding non-malignant cells, and non-cellular components are involved in this process. While intercellular communication traditionally centers around chemokines, cytokines, inflammatory mediators, and growth factors, emerging pathways involving extracellular vesicles (EVs) are gaining increasing attention. The immunosuppressive TME is created and maintained in part by the large abundance of tumor-associated macrophages (TMAs), which are associated with drug resistance, poor prognosis, and have emerged as potential targets for cancer immunotherapy. TMAs are highly dynamic, and can be polarized into either M1 or M2-like macrophages. EVs are efficient cell-cell communication molecules that have been catapulted to the center of TMA polarization. In this article, we provide detailed examination of the determinative role of EVs in sustaining the TME through mediating crosstalk between tumor cells and tumor-associated macrophages., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Coronary microvascular dysfunction (CMD) refers to a group of disorders affecting the structure and function of coronary microcirculation and is associated with an increased risk of major adverse cardiovascular events. At present, great progress has been made in the diagnosis of CMD, but there is no specific treatment for it because of the complexity of CMD pathogenesis. Vascular dysfunction is one of the important causes of CMD, but previous reviews mostly considered microvascular dysfunction as a whole abnormality so the obtained conclusions are skewed. The coronary microvascular function is co-regulated by multiple mechanisms, and the mechanisms by which microvessels of different luminal diameters are regulated vary. The main purpose of this review is to revisit the mechanisms by which coronary microvessels at different diameters regulate coronary microcirculation through integrated sequential activation and briefly discuss the pathogenesis, diagnosis, and treatment progress of CMD from this perspective., (© 2022. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

Recent years have witnessed the emergence of innovative analytical methods with high sensitivity and spatiotemporal resolution that allowed qualitative and quantitative analysis to be carried out at single-cell and subcellular levels. Electrochemiluminescence (ECL) is a unique chemiluminescence of high-energy electron transfer triggered by electrical excitation. The ingenious combination of electrochemistry and chemiluminescence results in the distinct advantages of high sensitivity, a wide dynamic range and good reproducibility. Specifically, single-cell ECL (SCECL) analysis with excellent spatiotemporal resolution has emerged as a promising toolbox in bioanalysis for revealing individual cells' heterogeneity and stochastic processes. This review focuses on advances in SCECL analysis and bioimaging. The history and recent advances in ECL probes and strategies for system design are briefly reviewed. Subsequently, the latest advances in representative SCECL analysis techniques for bioassays, bioimaging and therapeutics are also highlighted. Then, the current challenges and future perspectives are discussed.

Purpose: To study the relationship between the TyG index and the risk of AAC., Methods: We enrolled 1,486 participants from the National Health and Nutrition Examination Survey (NHANES). The TyG index was calculated in the log-transformed of triglycerides multipled by glucose, and the presence of AAC was diagnosed as AAC score above than 0., Results: Our suggested found that TyG level was positively correlated with the presence of AAC and log-transformed AAC score. After adjusted for other variables, comparing with the lowest quartile of TyG index, the highest quartile of TyG level was significantly associated with the presence of AAC (OR 2.12, 95%CI 1.05-4.35, p = 0.038) and severe AAC (OR 2.12, 95%CI 1.05-4.35, p = 0.038)., Conclusions: TyG index was significantly associated with the risk of AAC and severe AAC, which could be a marker in clinical practice., (© 2022. The Author(s).)

Background: Coronary microvascular dysfunction (CMD) may play an important role in various cardiovascular diseases, including HFpEF and both obstructive and non-obstructive coronary artery disease (CAD). To date, there has been no bibliometric analysis to summarize this field. Here, we aim to conduct a bibliometric analysis of CMD to determine the current status and frontiers in this field., Materials and Methods: Publications about CMD were taken from the Web of Science Core Collection database (WOSCC). WOSCC's literature analysis wire, the VOSviewer 1.6.16, and CiteSpace 5.1.3 were used to conduct the analysis., Results: A total of 785 publications containing 206 reviews and 579 articles are included in the sample. The leading authors are Iacopo Olivotto, Paolo G. Camici, and Carl J. Pepine. The most productive institutions are the University of Florence, Cedars Sinai Medical Center, and Harvard University. The most productive countries are the USA, Italy, and England. There are a total of 237 journals that contribute to this field, and the leading journals in our study were the International Journal of Cardiology, the European Heart Journal and the JACC. From 2012 to 2021, the top three most-cited articles focused on the association between HFpEF and CMD. The important keywords are heart failure, hypertrophic cardiomyopathy, chest pain, women, coronary flow reserve (CFR), endothelial dysfunction and prognostic value. "Positron emission tomography" shows the strongest burst strength, followed by "blow flow" and "artery." The keywords that started to burst from 2015 are particularly emphasized, including "heart failure," "coronary flow reserve," and "management.", Conclusion: Studies about CMD are relatively limited, and the largest contribution comes from the USA, Italy and England. More studies are needed, and publications from other countries should be enhanced. The main research hotspots in the CMD field include CMD in patients with HFpEF, sex differences, the new methods of diagnosis for CMD, and the effective treatment of CMD. Attention should be given to CMD in patients with HFpEF, and untangling the association between CMD and HFpEF could be helpful in the development of physiology-stratified treatment for patients with CMD and HFpEF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lin, Wu, Gao, Wang and Huang.)

Background: Lipoprotein (a) [Lp(a)] is an independent risk factor for coronary artery disease (CAD). Recent studies have indicated that statins tend to increase Lp(a) levels by 10-20%. However, the association of statin-mediated increases in Lp(a) levels with CAD has not been determined.  METHODS: This study included 488 patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI). Lp(a) levels were measured at baseline and 1 month after statin therapy. The study endpoints were major adverse cardiovascular events (MACE). Hazard ratios for the MACE were adjusted for potential confounder using Cox regression., Results: After statin therapy, the mean level of Lp(a) increased by 19.3% from baseline. Lp(a) levels increased in 307 patients (62.9%) with a median elevation of 4.1 mg/dL. Patients with an increase in Lp(a) were at higher risk for MACE than those without an increase in Lp(a) (p = 0.044). Subgroup analyses revealed that a mild-to-moderate increase in Lp(a) was not associated with MACE, whereas there was a strong correlation between the highest quartile increase in Lp(a) (≥ 10.1 mg/dL) and MACE (HR = 2.29, 95%CI = 1.36-3.84, p = 0.002). This correlation was independent of baseline Lp(a) levels but not independent of on-statin Lp(a) levels., Conclusions: Severe increases in Lp(a) following statin therapy raise the risk of MACE, but a mild-to-moderate increase in Lp(a) may not affect the cardiovascular prognosis of CAD patients. Even if the baseline Lp(a) levels are low, it is necessary to continue testing for Lp(a) concentration at least once after statin., (© 2022. The Author(s).)

Mitochondria are important organelles whose primary role is generating energy through the oxidative phosphorylation (OXPHOS) system. Cardiomyopathy, a common clinical disorder, is frequently associated with pathogenic mutations in nuclear and mitochondrial genes. To date, a growing number of nuclear gene mutations have been linked with cardiomyopathy; however, knowledge about mitochondrial tRNAs (mt-tRNAs) mutations in this disease remain inadequately understood. In fact, defects in mt-tRNA metabolism caused by pathogenic mutations may influence the functioning of the OXPHOS complexes, thereby impairing mitochondrial translation, which plays a critical role in the predisposition of this disease. In this review, we summarize some basic knowledge about tRNA biology, including its structure and function relations, modification, CCA-addition, and tRNA import into mitochondria. Furthermore, a variety of molecular mechanisms underlying tRNA mutations that cause mitochondrial dysfunctions are also discussed in this article.

One new lignan sinensiol H ( 1 ) and two new bisnorlignans, sinensiols I and J ( 2 and 3 ), along with three known compounds were isolated from the whole plants of Selaginella sinensis . Their structures were elucidated on the basis of 1D and 2D NMR spectroscopy as well as high-resolution mass spectrometry. The absolute configuration of 1 was established by ECD calculation. Compounds 2 and 3 represent rare examples of naturally occurring 9,9'-bisnorlignans. All the isolated compounds were assayed for their inhibitory effects on LPS-induced nitric oxide production in RAW 264.7 macrophages., (Copyright © 2022, Zhu et al.)