PLIN5 Suppresses Lipotoxicity and Ferroptosis in Cardiomyocyte via Modulating PIR/NF-κB Axis.

Cardiomyocyte lipotoxicity and ferroptosis are the key to the development of diabetic cardiomyopathy (DCM). Perilipin 5 (PLIN5) is perceived as a significant target of DCM. This study aimed to focus on the role and mechanism of PLIN5 on lipotoxicity and ferroptosis in DCM.Following transfection, mouse cardiomyocytes HL-1 were induced by 0.1 mM palmitic acid (PA) to set up lipotoxic cardiomyocyte models. The cell viability and lipid accumulation were evaluated by cell counting kit-8 assay and Oil red O staining, respectively. Ferrous ion (Fe2+), glutathione (GSH), malondialdehyde (MDA), and reactive oxygen species (ROS) levels were determined to verify the effects of PLIN5 or Pirin (PIR) on ferroptosis. Quantitative real-time reverse transcription polymerase chain reaction or Western blot was performed for quantitative analysis.PLIN5 overexpression promoted the viability, GSH level, and expression of GPX4/PIR/intracellular P65, yet suppressed lipid accumulation, level of Fe2+/MDA/ROS, and expression of interleukin (IL) -1ß/IL-18/intranuclear P65 in PA-stimulated HL-1 cells. PIR silencing counteracted the roles of PLIN5 overexpression in PA-stimulated HL-1 cells.PLIN5 suppresses lipotoxicity and ferroptosis in cardiomyocyte via modulating PIR/NF-κB axis, hinting its potential as a therapeutic target in DCM.

Source-specific probabilistic health risk assessment of heavy metals in surface water of the Yangtze River Basin.

The detrimental effects of heavy metal accumulation on both ecosystems and public health have raised widespread concern. Source-specific risk assessment is crucial for developing effective strategies to prevent and control heavy metal contamination in surface water. This study aims to investigate the contamination characteristics of heavy metals in the Yangtze River Basin, identifying the pollution sources, assessing the risk levels, and further evaluating the health risks to humans. The results indicated that the average concentrations of heavy metals were ranked as follows: zinc (Zn) > arsenic (As) > copper (Cu) > chromium (Cr) > cadmium (Cd) > nickel (Ni) > lead (Pb), with average concentrations of 38.02 µg/L, 4.34 µg/L, 2.53 µg/L, 2.10 µg/L, 1.17 µg/L, 0.84 µg/L, and 0.32 µg/L, respectively, all below the WHO 2017 standards for safe drinking water. The distribution trend indicates higher concentrations in the upper and lower reaches and lower concentrations in the mid-reaches of the river. By integrating the Absolute Principal Component Scores-Multiple Linear Regression (APCS-MLR) receptor model and Positive Matrix Factorization (PMF) model, the main sources of heavy metals were identified as industrial activities (APCS-MLR: 41.3 %; PMF: 42.1 %), agricultural activities (APCS-MLR: 30.1 %; PMF: 27.4 %), and unknown mix sources (APCS-MLR: 29.1 %; PMF: 30.4 %). The calculation of the hazard index (HI) for both children and adults was <1, indicating no non-carcinogenic or carcinogenic risks. Based on the source-specific risk assessment, agricultural activities contribute the most to non-carcinogenic risks, while industrial activities pose the greatest contribution to carcinogenic risks. This study offers a reference for monitoring heavy metals and controlling health risks to residents, and provides crucial evidence for the utilization and protection of surface water in the Yangtze River Basin.

The effects of respiratory muscle training on respiratory function and functional capacity in patients with early stroke: a meta-analysis.

BACKGROUND: Respiratory muscle training is a continuous and standardized training of respiratory muscles, but the evidence of the effects on early stroke patients is not clear. This meta-analysis aimed to investigate the effects of respiratory muscle training on respiratory function and functional capacity in patients with early stroke. METHODS: PubMed, Embase, PEDro, ScienceDirect, AMED, CINAHL, and China National Knowledge Infrastructure databases were searched from inception to December 8, 2023 for articles about studies that 1) stroke patients with age ≥ 18 years old. Early stroke < 3 months at the time of diagnosis, 2) respiratory muscle training, including inspiratory and expiratory muscle training, 3) the following measurements are the outcomes: respiratory muscle strength, respiratory muscle endurance, pulmonary function testing, dyspnea fatigue score, and functional capacity, 4) randomized controlled trials. Studies that met the inclusion criteria were extracted data and appraised the methodological quality and risk of bias using the Physiotherapy Evidence Database scale and the Cochrane Risk of Bias tool by two independent reviewers. RevMan 5.4 with a random effect model was used for data synthesis and analysis. Mean differences (MD) or standard mean differences (SMD), and 95% confidence interval were calculated (95%CI). RESULTS: Nine studies met inclusion criteria, recruiting 526 participants (mean age 61.6 years). Respiratory muscle training produced a statistically significant effect on improving maximal inspiratory pressure (MD = 10.93, 95%CI: 8.51-13.36), maximal expiratory pressure (MD = 9.01, 95%CI: 5.34-12.69), forced vital capacity (MD = 0.82, 95%CI: 0.54-1.10), peak expiratory flow (MD = 1.28, 95%CI: 0.94-1.63), forced expiratory volume in 1 s (MD = 1.36, 95%CI: 1.13-1.59), functional capacity (SMD = 0.51, 95%CI: 0.05-0.98) in patients with early stroke. Subgroup analysis showed that inspiratory muscle training combined with expiratory muscle training was beneficial to the recovery of maximal inspiratory pressure (MD = 9.78, 95%CI: 5.96-13.60), maximal expiratory pressure (MD = 11.62, 95%CI: 3.80-19.43), forced vital capacity (MD = 0.87, 95%CI: 0.47-1.27), peak expiratory flow (MD = 1.51, 95%CI: 1.22-1.80), forced expiratory volume in 1 s (MD = 0.76, 95%CI: 0.41-1.11), functional capacity (SMD = 0.61, 95%CI: 0.08-1.13), while inspiratory muscle training could improve maximal inspiratory pressure (MD = 11.60, 95%CI: 8.15-15.05), maximal expiratory pressure (MD = 7.06, 95%CI: 3.50-10.62), forced vital capacity (MD = 0.71, 95%CI: 0.21-1.21), peak expiratory flow (MD = 0.84, 95%CI: 0.37-1.31), forced expiratory volume in 1 s (MD = 0.40, 95%CI: 0.08-0.72). CONCLUSIONS: This study provides good-quality evidence that respiratory muscle training is effective in improving respiratory muscle strength, pulmonary function, and functional capacity for patients with early stroke. Inspiratory muscle training combined with expiratory muscle training seems to promote functional recovery in patients with early stroke more than inspiratory muscle training alone. TRIAL REGISTRATION: Prospero registration number: CRD42021291918.

Influence of TMX2-CTNND1 polymorphism on cortical thickness in schizophrenia and their unaffected sibling: an exploratory study based on target region sequencing.

OBJECTIVES: The advancement of neuroimaging and genetic research has revealed the presence of morphological abnormalities and numerous risk genes, along with their associations. METHODS: The cortical thickness of 129 schizophrenia patients, 42 unaffected siblings of patients and 112 healthy controls was measured, and the candidate genes were sequenced. Comparisons of cortical thickness (including 68 regions of Desikan-Kiliany atlas) and genetic variants (within 108 risk genes for schizophrenia) among the three groups were made, and correlation analyses were performed between cortical thickness, clinical symptoms, cognitive tests like N-back and logical memory test and genetic variants. RESULTS: The study revealed that schizophrenia patients had significantly thinner bilateral frontal, temporal, and parietal gyrus compared to healthy controls and unaffected siblings. Furthermore, association analyses in target genes found 4 SNVs were significantly associated with schizophrenia diagnosis, including TMX2-CTNND1 (SNV20673) (PFDR = 0.008) and CENPM (rs35542507, rs41277477, rs73165153) (PFDR = 0.030). Additionally, cortical thickness in right pars triangularis was observed to be thinner in carriers of the SNV20673 variant compared to non-carriers (PFDR = 0.048). Lastly, a positive correlation was found between right pars triangularis cortical thickness and logical memory in schizophrenia patients (r = 0.199, p = 0.032). CONCLUSIONS: This study identified regional morphological abnormalities in schizophrenia, including the right homologue of Broca's area, which was associated with a risk variant affecting delta-1 catenin and affected logical memory. These findings suggest a potential association between candidate gene loci, cortical thickness, and schizophrenia.

Tracing sulfate sources and transformations of surface water using multiple isotopes in a mining-rural-urban agglomeration area.

Rapid urbanization and mining activities are exacerbating sulfate (SO42-) pollution in surface water, and the information on its sources and transformations is crucial for understanding the sulphur cycle in mining areas. In this study, the SO42- in the surface water of Huaibei mining area were monitored and the main sources of pollution and biogeochemical processes were identified using stable isotopes (δD, δ18O-H2O, δ34S-SO42- and δ18O-SO42-) and water chemistry. The results demonstrated the SO42- content in the Huihe River and Linhuan subsidence water area (SWA) is higher than that in other rivers and SWAs, which exceeded the environmental quality standard of surface water. The SO42- content of different rivers and SWAs showed seasonal differences, and the dry season was higher than the wet season. In addition, the SO42- in Tuohe River and Suihe River is primarily caused by urban sewage and agriculture activities, while in Zhonghu and Shuoxihu SWA is mainly contributed by natural evaporate dissolution. Notably, the input of SO42- in the Huihe River and Linhuan SWA caused by mining activities cannot be disregarded. The aerobic environment and isotopic fractionation of surface water indicate that sulfide oxidation is not the major cause of SO42- formation. This work has revealed the multiple sources and transformation mechanisms of SO42-, and provided a reference for the development of comprehensive management and effective remediation strategies of SO42- contamination in surface water around mining areas.

Identification of nitrate accumulation mechanism of surface water in a mining-rural-urban agglomeration area based on multiple isotopic evidence.

The accumulation of nitrate (NO3-) in surface waters resulting from mining activities and rapid urbanization has raised widespread concerns. Therefore, it is crucial to develop a nitrate transformation information system to elucidate the nitrogen cycle and ensure sustainable water quality management. In this study, we focused on the main river and subsidence area of the Huaibei mining region to monitor the temporal and spatial variations in the NO3- content. Multiple isotopes (δD, δ18O-H2O, δ15N-NO3-, δ18O-NO3-, and δ15N-NH4+) along with water chemistry indicators were employed to identify the key mechanisms responsible for nitrate accumulation (e.g., nitrification and denitrification). The NO3- concentrations in surface water ranged from 0.28 to 7.50 mg/L, with NO3- being the predominant form of nitrogen pollution. Moreover, the average NO3- levels were higher during the dry season than during the wet season. Nitrification was identified as the primary process driving NO3- accumulation in rivers and subsidence areas, which was further supported by the linear relationship between δ15N-NO3- and δ15N-NH4+. The redox conditions and the relationship between δ15N-NO3- and δ18O-NO3-, and lower isotope enrichment factor of denitrification indicated that denitrification was weakened. Phytoplankton preferentially utilized available NH4+ sources while inhibiting NO3- assimilation because of their abundance. These findings provide direct evidence regarding the mechanism underlying nitrate accumulation in mining areas, while aiding in formulating improved measures for effectively managing water environments to prevent further deterioration.

Autosomal recessive intellectual disability caused by compound heterozygous variants of the EEF1D gene in a Chinese family.

BACKGROUND: Intellectual disability is a prevalent neurodevelopmental disorder, with the majority of affected children exhibiting global developmental delay before the age of 5 years. In recent years, certain children have been found to carry homozygous variations of the EEF1D gene, leading to autosomal recessive intellectual disability. However, the pathogenicity of compound heterozygous variations in this gene remains largely unknown. METHODS: Trio whole-exome sequencing and copy number variation sequencing were done for the genetic etiological diagnosis of a 3-year and 11-month-old Chinese boy who presented with brachycephaly, severe to profound global developmental delay, and hypotonia in the lower limbs. RESULTS: In this case, compound heterozygous variants of the EEF1D gene were found in the child through trio whole-exome sequencing; one was a splice variant (NM_032378.6:c.1905+1G>A) inherited from his father, and the other was a nonsense variant (NM_032378.6:c.676C>T) inherited from his mother. The nonsense variant leads to the production of a premature termination (p.Gln226*). These variations have the ability to explain the clinical phenotypes of the child. CONCLUSIONS: Our study expands the variation spectrum and provides compelling evidence for EEF1D as a candidate gene for autosomal recessive intellectual disability. However, due to the deficient number of reported cases, researchers need to further study EEF1D and supplement the clinical phenotypes and treatment measures.

Hippocampal circAnk3 Deficiency Causes Anxiety-like Behaviors and Social Deficits by Regulating the miR-7080-3p/IQGAP1 Pathway in Mice.

BACKGROUND: Circular RNAs are highly enriched in the synapses of the mammalian brain and play important roles in neurological function by acting as molecular sponges of microRNAs. circAnk3 is derived from the 11th intron of the ankyrin-3 gene, Ank3, a strong genetic risk factor for neuropsychiatric disorders; however, the function of circAnk3 remains elusive. In this study, we investigated the function of circAnk3 and its downstream regulatory network for target genes in the hippocampus of mice. METHODS: The DNA sequence from which circAnk3 is generated was modified using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/Cas9) technology, and neurobehavioral tests (anxiety and depression-like behaviors, social behaviors) were performed in circAnk3+/- mice. A series of molecular and biochemical assays were used to investigate the function of circAnk3 as a microRNA sponge and its downstream regulatory network for target genes. RESULTS: circAnk3+/- mice exhibited both anxiety-like behaviors and social deficits. circAnk3 was predominantly located in the cytoplasm of neuronal cells and functioned as a miR-7080-3p sponge to regulate the expression of Iqgap1. Inhibition of miR-7080-3p or restoration of Iqgap1 in the hippocampus ameliorated the behavioral deficits of circAnk3+/- mice. Furthermore, circAnk3 deficiency decreased the expression of the NMDA receptor subunit GluN2a and impaired the structural plasticity of dendritic synapses in the hippocampus. CONCLUSIONS: Our results reveal an important role of the circAnk3/miR-7080-3p/IQGAP1 axis in maintaining the structural plasticity of hippocampal synapses. circAnk3 might offer new insights into the involvement of circular RNAs in neuropsychiatric disorders.

Transparent silk fibroin film-facilitated infected-wound healing through antibacterial, improved fibroblast adhesion and immune modulation.

The clinical application of regenerated silk fibroin (RSF) films for wound treatment is restricted by its undesirable mechanical properties and lack of antibacterial activity. Herein, different pluronic polymers were introduced to optimize their mechanical properties and the RSF film with 2.5% pluronic F127 (RSFPF127) stood out to address the above issues owing to its satisfactory mechanical properties, hydrophilicity, and transmittance. Diverse antibacterial agents (curcumin, Ag nanoparticles, and antimicrobial peptide KR-12) were separately encapsulated in RSFPF127 to endow it with antibacterial activity. In vitro experiments revealed that the medicated RSFPF127 could persistently release drugs and had desirable bioactivities toward killing bacteria, promoting fibroblast adhesion, and modulating macrophage polarization. In vivo experiments revealed that medicated RSFPF127 not only eradicated methicillin-resistant Staphylococcus aureus in the wound area and inhibited inflammatory responses, but also facilitated angiogenesis and re-epithelialization, regardless of the types of antibacterial agents, thus accelerating the recovery of infected wounds. These results demonstrate that RSFPF127 is an ideal matrix platform to load different types of drugs for application as wound dressings.

Basin-wide tracking of nitrate cycling in Yangtze River through dual isotope and machine learning.

The nitrate (NO3-) input has adversely affected the water quality and ecological function in the whole basin of the Yangtze River. The protection of water sources and implementation of "great protection of Yangtze River" policy require large-scale information on water contamination. In this study, dual isotope and Bayesian mixing model were used to research the transformation and sources of nitrate. Chemical fertilizers contribute 76 % of the nitrate sources in the upstream, while chemical fertilizers were also dominant in the midstream (39 %) and downstream (39 %) of Yangtze River. In addition, nitrification process occurred in the whole basin. Four machine learning models were used to relate nitrate concentrations to explanatory variables describing influence factors to predict nitrate concentrations in the whole basin of Yangtze River. The anthropogenic and natural factors, such as rainfall, GDP and population were chosen to take as predictor variables. The eXtreme Gradient Boosting (XGBoost) model for nitrate has a better predictive performance with an R2 of 0.74. The predictive models of nitrate concentrations will help identify the nitrate distribution and transport in the whole Yangtze River basin. Overall, this study represents the first basin-wide data-driven assessment of the nitrate cycling in the Yangtze River basin.

CaO2-Cu2O micromotors accelerate infected wound healing through antibacterial functions, hemostasis, improved cell migration, and inflammatory regulation.

During the wound tissue healing process, the relatively weak driving forces of tissue barriers and concentration gradients lead to a slow and inefficient penetration of bioactive substances into the wound area, consequently showing an impact on the effectiveness of deep wound healing. To overcome these challenges, we constructed biocompatible CaO2-Cu2O "micromotors". These micromotors reacted with the fluids at the wound site, releasing oxygen bubbles and propelling particles deep into the wound tissue. In vitro experimental results revealed that these micromotors not only exhibited antibacterial and hemostatic functions but also facilitated the migration of dermal fibroblasts and vascular endothelial cells, while modulating the inflammatory microenvironment. A methicillin-resistant Staphylococcus aureus infected full-thickness-wound model was created in rats, in which CaO2-Cu2O micromotors markedly expedited the wound healing process. Specifically, CaO2-Cu2O provided a sterile microenvironment for wounds and increased the amounts of M1-type macrophages during infection and inflammation. During the proliferation and remodeling stages, the amount of M1 macrophages gradually decreased, while the amount of M2 macrophages increased, and CaO2-Cu2O did not prolong the inflammatory period. Furthermore, the introduction of a regenerated silk fibroin (RSF) film on the wound surface successfully enhanced the therapeutic effects of CaO2-Cu2O against the infected wound. The combined application of oxygen-producing CaO2-Cu2O micromotors and a RSF film demonstrates significant therapeutic potential and emerges as a promising candidate for the treatment of infected wounds.

Profile and mental health characterization of childhood overprotection/overcontrol experiences among Chinese university students: a nationwide survey.

Introduction: The childhood experiences of being overprotected and overcontrolled by family members have been suggested to be potentially traumatic. However, the possible associated factors of these experiences among young people are still not well studied. This study aimed to partly fill such gaps by a relatively large, nationwide survey of Chinese university students. Methods: A total of 5,823 university students across nine different provinces in China were included by the convenience sampling method in the data analyses. All participants completed the overprotection/overcontrol (OP/OC) subscale in a recently developed 33-item childhood trauma questionnaire (CTQ- 33). Data were also collected on all participants' socio-demographic profiles and characterization of mental health. Binary logistic regression was conducted to investigate the associated socio-demographic and psychological factors of OP/ OC. Results: The prevalence of childhood OP/OC was estimated as 15.63% (910/5,823) based on a cutoff OP/OC subscale score of ≥ 13. Binary logistic regression suggested that being male, being a single child, having depression, having psychotic-like experiences, lower family functioning, and lower psychological resilience were independently associated with childhood OP/OC experiences (all corrected-p < 0.05). The OP/OC was also positively associated with all the other trauma subtypes (abuses and neglects) in the CTQ-33, while there are both shared and unique associated factors between the OP/OC and other trauma subtypes. Post-hoc analyses suggested that OP/OC experiences were associated with depression in only females and associated with anxiety in only males. Discussion: Our results may provide initial evidence that childhood OP/OC experiences would have negative effects on young people's mental health which merits further investigations, especially in clinical populations.

TRAF6 triggers Mycobacterium-infected host autophagy through Rab7 ubiquitination.

Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an E3 ubiquitin ligase that is extensively involved in the autophagy process by interacting with diverse autophagy initiation and autophagosome maturation molecules. However, whether TRAF6 interacts with lysosomal proteins to regulate Mycobacterium-induced autophagy has not been completely characterized. Herein, the present study showed that TRAF6 interacted with lysosomal key proteins Rab7 through RING domain which caused Rab7 ubiquitination and subsequently ubiquitinated Rab7 binds to STX17 (syntaxin 17, a SNARE protein that is essential for mature autophagosome), and thus promoted the fusion of autophagosomes and lysosomes. Furthermore, TRAF6 enhanced the initiation and formation of autophagosomes in Mycobacterium-induced autophagy in both BMDMs and RAW264.7 cells, as evidenced by autophagic flux, colocalization of LC3 and BCG, autophagy rates, and autophagy-associated protein expression. Noteworthy to mention, TRAF6 deficiency exacerbated lung injury and promoted BCG survival. Taken together, these results identify novel molecular and cellular mechanisms by which TRAF6 positively regulates Mycobacterium-induced autophagy.

A diagnostic model for sepsis-induced acute lung injury using a consensus machine learning approach and its therapeutic implications.

BACKGROUND: A significant proportion of septic patients with acute lung injury (ALI) are recognized late due to the absence of an efficient diagnostic test, leading to the postponed treatments and consequently higher mortality. Identifying diagnostic biomarkers may improve screening to identify septic patients at high risk of ALI earlier and provide the potential effective therapeutic drugs. Machine learning represents a powerful approach for making sense of complex gene expression data to find robust ALI diagnostic biomarkers. METHODS: The datasets were obtained from GEO and ArrayExpress databases. Following quality control and normalization, the datasets (GSE66890, GSE10474 and GSE32707) were merged as the training set, and four machine learning feature selection methods (Elastic net, SVM, random forest and XGBoost) were applied to construct the diagnostic model. The other datasets were considered as the validation sets. To further evaluate the performance and predictive value of diagnostic model, nomogram, Decision Curve Analysis (DCA) and Clinical Impact Curve (CIC) were constructed. Finally, the potential small molecular compounds interacting with selected features were explored from the CTD database. RESULTS: The results of GSEA showed that immune response and metabolism might play an important role in the pathogenesis of sepsis-induced ALI. Then, 52 genes were identified as putative biomarkers by consensus feature selection from all four methods. Among them, 5 genes (ARHGDIB, ALDH1A1, TACR3, TREM1 and PI3) were selected by all methods and used to predict ALI diagnosis with high accuracy. The external datasets (E-MTAB-5273 and E-MTAB-5274) demonstrated that the diagnostic model had great accuracy with AUC value of 0.725 and 0.833, respectively. In addition, the nomogram, DCA and CIC showed that the diagnostic model had great performance and predictive value. Finally, the small molecular compounds (Curcumin, Tretinoin, Acetaminophen, Estradiol and Dexamethasone) were screened as the potential therapeutic agents for sepsis-induced ALI. CONCLUSION: This consensus of multiple machine learning algorithms identified 5 genes that were able to distinguish ALI from septic patients. The diagnostic model could identify septic patients at high risk of ALI, and provide potential therapeutic targets for sepsis-induced ALI.

Polysaccharide-Based Supramolecular Hydrogel Coatings with Corrosion Barrier Zone for Protection of Patina Bronze.

Protective coatings for bronze relics should adhere to the basic principles of cultural relic preservation, such as not altering the color and appearance of the artifacts, and being moderately combined with the artifacts to resist erosion due to external environments (such as water and gas). This paper presents the development of a physically crosslinked supramolecular hydrogel produced from guanidinium-based chitosan (GC). The hydrogel exhibits the excellent adsorption protection of bronze, and the addition of clay enhances the water barrier properties of the chitosan film. The supramolecular interaction between sodium polyacrylate/GC/clay confers corrosion buffering capability to the hydrogel coating in corrosive environments, and the gel coating can be self-healing at room temperature for 24 h. The fabricated nanocomposites were comprehensively characterized using various methods (Fourier transform infrared spectroscopy, X-ray diffraction, thermogravimetric analysis, X-ray photoelectron spectroscopy, scanning electron microscopy, etc.). The electrochemical properties of coated specimens were evaluated, and the impedance spectrum revealed a large impedance arc indicating high charge resistance, which has a corrosion resistance effect.

Polygenic risk for schizophrenia and the language network: Putative compensatory reorganization in unaffected siblings.

Language-related symptoms, such as disorganized, impoverished speech and communicative behaviors, are one of the core features of schizophrenia. These features most strongly correlate with cognitive deficits and polygenic risk among various symptom dimensions of schizophrenia. Nevertheless, unaffected siblings with genetic high-risk fail to show consistent deficits in language network (LN), indicating that either (1) polygenic risk has no notable effect on LN and/or (2) siblings show compensatory changes in opposing direction to patients. To answer this question, we related polygenic risk scores (PRS) to the region-level, tract-level, and systems-level structure (cortical thickness and fiber connectivity) of LN in 182 patients, 48 unaffected siblings and 135 healthy controls. We also studied the relationships between symptoms, language-related cognition, social functioning and LN structure. We observed a significantly lower thickness in LN (especially the Broca's, Wernicke's area and their right homologues) in patients. Siblings had a distinctly higher thickness in parts of the LN and a more pronounced small-world-like structural integration within the LN. Patients with reduced LN thickness had higher PRS, more disorganization and impoverished speech with lower language-related cognition and social functioning. We conclude that the genetic susceptibility and putative compensatory changes for schizophrenia operate, in part, via key regions in the Language Network.

Effects of first-line antidiabetic drugs on the improvement of arterial stiffness: A Bayesian network meta-analysis.

BACKGROUND: Changes in vascular function are closely associated with the development of cardiovascular disease (CVD). Pulse wave velocity (PWV) is a potential indicator of vascular dysfunction; it allows noninvasive assessment of arterial stiffness. Currently, evidence for the effects of different classes of antidiabetic drugs on arterial stiffness remains limited. In this study, a network meta-analysis (NMA) was performed to explore the associations between changes in arterial stiffness and first-line antidiabetic drugs by evaluating PWV in patients with different metabolic abnormalities. METHODS: We systematically searched several electronic databases for randomized controlled trials (RCTs) published from inception until 25 August 2022, without language restrictions. The primary outcome was the change in PWV (ΔPWV) in all included studies; subgroup analysis was performed for patients with abnormal glucose metabolism, including prediabetes and diabetes mellitus. NMA was performed to calculate the mean differences (MDs) with 95% confidence intervals (CIs) as effect sizes to evaluate the ΔPWV. RESULTS: Among the 2257 candidate articles identified in the initial search, 18 RCTs were eventually included in the analysis. In all studies, two classes of new antidiabetic drugs, glucagon-like peptide-1 receptor (GLP-1R) agonists and sSodium-glucose co-transporter 2 (SGLT-2) inhibitors, improved arterial stiffness by decreasing PWV compared with placebo (MD = -1.11, 95% CI: -1.94 to 0.28) and (MD = -0.76, 95% CI: -1.45 to -0.08). A conventional antidiabetic drug, metformin, also showed similar efficacy compared with placebo (MD = -0.73, 95% CI: -1.33 to -0.12). Finally, in subgroup studies of patients with abnormal glucose metabolism diseases, GLP-1R agonists (MD = -1.06, 95% CI: -2.05 to -0.10) significantly decreased PWV compared with placebo. CONCLUSION: Three classes of antidiabetic drugs-GLP-1R agonists, SGLT-2 inhibitors, and metformin-have the potential to improve arterial stiffness. Among the six classes of antidiabetic drugs analyzed, GLP-1R agonists constitute the only class of drugs that improves arterial stiffness in patients with abnormal glucose metabolism diseases.

Occurrence and source analysis of heavy metals and dissolved organic matter in Nanyi Lake, Anhui Province.

Nanyi Lake is a tributary in the lower reaches of the Yangtze River and the largest freshwater lake in southern Anhui. Anthropogenic activities have significantly affected the lake with the rapid development of the surrounding economy in recent years. This study collected a total of 39 × 2 water samples of surface water and overlying water, detected the heavy metal concentrations (As, Cr, Cu, Mn, Ni, Pb, Sb, Zn, Fe, Cd), and analyzed the spectral characteristics of the dissolved organic matter (DOM). The results demonstrated that the concentrations of heavy metals (As, Cr, Cu, Mn, Ni, Pb, Sb, Zn, Fe, Cd) in the surface water were 1.00-7.78, 0.40-5.59, 0.20-4.52, 20.00-269.50, 0.40-5.56, 0.20-5.06, 1.00-7.64, 20.00-252.50, 60.00-590.00, and 0.04-0.60, respectively (unit: µg L-1). The risk assessment showed that the carcinogenic risks of heavy metals (As, Cr, Cd) through drinking water were ranged from 10-7 to 10-4a-1 in Nanyi Lake, and Cr was the main carcinogen which should be the focus of environmental health risk management. The average personal non-carcinogenic risks of heavy metals (Cu, Mn, Ni, Pb, Sb, Zn, Fe) were ranged from 10-9 to 10-13a-1, and considered to be acceptable risk level. The contour map of spatial distribution demonstrated different degrees of heavy metals (except Zn) enrichment near the Langchuan River in the East Lake District. Parallel factor analysis showed that the main components of DOM in Nanyi Lake were tryptophan like, fulvic acid like, and tyrosine like, and the dissolved organic matter was primarily derived from autogenous endogenous sources. The heavy metals Cr, Ni, Pb, Fe, Cd, and HIX in the surface water of West Lake were significantly positively correlated, among which Ni, Fe and C2 were significantly negatively correlated (P < 0.05), Mn and BIX demonstrated extremely significant positive correlations (P < 0.01), while no significant correlation was observed between heavy metals and the DOM indexes in the surface water of the East Lake. The principal component and correlation analysis showed that the heavy metals in Nanyi Lake were primarily derived from the production wastewater discharged by the surrounding industrial and mining enterprises through the rivers input, followed by the non-point source runoff input of the surrounding agricultural production and lake aquaculture.

The effects of programmed optical zones on achieved corneal refractive power with myopic astigmatism after small incision lenticule extraction (SMILE): a vector analysis.

PURPOSE: To evaluate the effects of different programmed optical zones (POZs) on achieved corneal refractive power (CRP) with myopic astigmatism after small incision lenticule extraction (SMILE). METHODS: In total, 113 patients (113 eyes) were included in this retrospective study. The eyes were divided into two groups according to POZ: group A (6.5, 6.6, and 6.7 mm, n = 59) and group B (6.8, 6.9, and 7.0 mm, n = 54). Fourier vector analysis was applied to evaluate the error values between the attempted and achieved corneal refractive power (CRP). Alpins vector analysis was used to calculate surgically induced astigmatism (SIA), difference vector (DV), magnitude of error (ME), and astigmatism correction index (ACI). Multivariate regression analysis was performed to assess potential factors associated with the error values. RESULTS: The error values in the group with large POZ were closer to zero, and significantly associated with the POZ at 2 and 4 mm of the cornea (ß = - 0.50, 95% confidence interval [CI] [- 0.80, - 0.20]; ß = - 0.37, 95% CI [- 0.63, - 0.10], P < 0.05, respectively). For the correction of astigmatism, the values of SIA, ME, and ACI were lower in group B than in group A (P < 0.05). The fitting curves between TIA and SIA were y = 0.83x + 0.19 (R2 = 0.84) and y = 1.05x + 0.04 (R2 = 0.90), respectively. CONCLUSIONS: Smaller POZs resulted in higher error values between the achieved- and attempted-CRP in the SMILE procedure, which should be considered when performing surgery.