A Mechanically Resilient Soft Hydrogel Improves Drug Delivery for Treating Post-Traumatic Osteoarthritis in Physically Active Joints.

Intra-articular delivery of disease-modifying osteoarthritis drugs (DMOADs) is likely to be most effective in early post-traumatic osteoarthritis (PTOA) when symptoms are minimal and patients are physically active. DMOAD delivery systems therefore must withstand repeated mechanical loading without affecting the drug release kinetics. Although soft materials are preferred for DMOAD delivery, mechanical loading can compromise their structural integrity and disrupt drug release. Here, we report a mechanically resilient soft hydrogel that rapidly self-heals under conditions resembling human running while maintaining sustained release of the cathepsin-K inhibitor L-006235 used as a proof-of-concept DMOAD. Notably, this hydrogel outperformed a previously reported hydrogel designed for intra-articular drug delivery, used as a control in our study, which neither recovered nor maintained drug release under mechanical loading. Upon injection into mouse knee joints, the hydrogel showed consistent release kinetics of the encapsulated agent in both treadmill-running and non-running mice. In a mouse model of aggressive PTOA exacerbated by treadmill running, L-006235 hydrogel markedly reduced cartilage degeneration. To our knowledge, this is the first hydrogel proven to withstand human running conditions and enable sustained DMOAD delivery in physically active joints, and the first study demonstrating reduced disease progression in a severe PTOA model under rigorous physical activity, highlighting the hydrogel's potential for PTOA treatment in active patients.

Application value of real-time 3D speckle tracking imaging in left atrial function evaluation of patients with paroxysmal atrial fibrillation.

OBJECTIVE: To evaluate left atrial volume and function in patients with paroxysmal atrial fibrillation (AF) combined with left atrial appendage thrombosis and patients with paroxysmal AF without left atrial appendage thrombosis by 3-dimensional speckle tracking imaging (3D-STI), and to explore the application value of this set of parameters in the evaluation of left atrial function in patients with paroxysmal AF. MATERIALS AND METHODS: A total of 40 patients with paroxysmal AF admitted from December 2018 to December 2020 were selected as the observation group. All patients with paroxysmal AF in the observation group underwent transesophageal echocardiography. According to the presence of left atrial appendage thrombosis, the patients were divided into the AF without thrombosis group (24 cases) and the AF with thrombosis group (16 cases). Thirty normal people were selected as control group who were chosen as having no heart-related disease. The left atrial volume parameters (Left atrial maximum volume LAVmax, Left atrial minimum volume LAVmin, Left atrial volume before atrial contraction LAVpre-A, Left atrial stroke volume LAEV), left atrial ejection fraction (LAEF) and left atrial strain parameters (Left atrial reservoir longitudinal strain LASr, Left atrial conduit longitudinal strain LAScd, Left atrial contraction longitudinal strain LASct, Left atrial reservoir circumferential strain LASr-c, Left atrial conduit circumferential strain LAScd-c, Left atrial contraction circumferential strain LASct-c) of the 3 groups were measured by 3D-STI. RESULTS: With the progression of paroxysmal AF, the left atrial volume increased, and the reservoir, conduit and contractile function were damaged. The left atrial volume continued to increase, and the reservoir, conduit and contractile function further decreased significantly in patients with AF combined with left atrial appendage thrombosis. LAEF was positively correlated with LASr and LASr_c. CONCLUSION: Real-time 3-dimensional spot tracking imaging (3D-STI) can evaluate the changes in left atrial volume and function in patients with paroxysmal AF, and has a certain reference value for clinical judgment of disease progression and prognosis.

The Chinese Version of the Compensatory ADHD Behaviors Scale (CABS): A Study on Reliability, Validity, and Clinical Utility.

Purpose: With the further development of attention-deficit/hyperactivity disorder (ADHD) research, more and more assessment tools related to ADHD have been used. However, there is still no measurement instrument to evaluate the compensatory behavior of ADHD in China. This study aimed to examine the reliability and validity of the Compensatory ADHD Behaviors Scale (CABS) adapted in Chinese and explore ecological characteristics in adults with ADHD using the CABS. Patients and Methods: Data were collected from a sample of 306 adults (Mage = 26.43 years, SD = 5.32; 46.08% male). The original version CABS was translated into Chinese using the forward and backward translation procedures. Participants completed the CABS and questionnaires assessing ADHD symptoms and executive function. We utilized content validity, exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and criterion validity to test the validity. Internal consistency and test-retest reliability were employed to test the reliability. Analysis of variance (ANOVA) was employed to compare ADHD subgroups based on gender, ADHD subtype, comorbidities, and medication status, while controlling for demographic variables as covariates. Results: CABS exhibited good construct validity (two factors: present-oriented and future-oriented), content validity (content validity index: 0.98), internal consistency reliability (Cronbach's alpha coefficient: 0.85 to 0.87) and test-retest reliability (intraclass correlation coefficient: 0.59 to 0.88). The results of CFA showed acceptable fitness for each subscale. CABS demonstrated significant associations with inattention symptoms and plan/organizational abilities. Medicated ADHD individuals scored higher on future-oriented effectiveness subscale of CABS than non-medicated (F = 6.106, p = 0.014). Conclusion: The results indicate that the Chinese CABS exhibited good validity and reliability. It can be considered a valid tool for assessing compensatory behaviors in Chinese adults with ADHD. Further research is needed to explore the connection between medication and compensatory behavior.

Screening and diagnosis of cardiovascular disease using artificial intelligence-enabled cardiac magnetic resonance imaging.

Cardiac magnetic resonance imaging (CMR) is the gold standard for cardiac function assessment and plays a crucial role in diagnosing cardiovascular disease (CVD). However, its widespread application has been limited by the heavy resource burden of CMR interpretation. Here, to address this challenge, we developed and validated computerized CMR interpretation for screening and diagnosis of 11 types of CVD in 9,719 patients. We propose a two-stage paradigm consisting of noninvasive cine-based CVD screening followed by cine and late gadolinium enhancement-based diagnosis. The screening and diagnostic models achieved high performance (area under the curve of 0.988 ± 0.3% and 0.991 ± 0.0%, respectively) in both internal and external datasets. Furthermore, the diagnostic model outperformed cardiologists in diagnosing pulmonary arterial hypertension, demonstrating the ability of artificial intelligence-enabled CMR to detect previously unidentified CMR features. This proof-of-concept study holds the potential to substantially advance the efficiency and scalability of CMR interpretation, thereby improving CVD screening and diagnosis.

Strong Angular Oscillation of Rotationally Resolved Differential Cross Section in the H + HD → H2 + D Reaction at the Collision Energy of 2.07 eV: Evidence of Geometric Phase Effects.

Geometric phase (GP) effects in chemical reactions are subtle quantum phenomena that are challenging to identify. In this work, we report a joint experimental and theoretical study of the H + HD → H2 + D reaction at a collision energy of 2.07 eV, which is far below the energy of the conical intersection of 2.53 eV. The rotationally state-resolved differential cross sections were measured by a crossed-beam experiment with the scheme of D-atom Rydberg tagging time-of-flight detection. Experimental angular distributions of three rotational states of H2 products exhibit notable variation near the backward scattering direction. Time-dependent quantum mechanics calculations (TDQMs) were carried out at the same collision energy, with and without the inclusion of GP. The experimental angular distributions are in good agreement with TDQM results with the inclusion of GP but do not agree with TDQM results without the inclusion of GP. This work demonstrates the existence of GP effects at energy far below the conical intersection.

Association between blood pressure variability and risk of kidney function decline in hypertensive patients without chronic kidney disease: a post hoc analysis of Systolic Blood Pressure Intervention Trial study.

BACKGROUND: Blood pressure variability (BPV) is a risk factor for poor kidney function independent of blood pressure (BP) in chronic kidney disease (CKD). Little is known about the association between kidney function decline and BPV in hypertensive patients without CKD. METHODS: A post-hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) was performed. BPV was measured as standard deviation (SD) and average real variability (ARV). Cox proportional hazard models were employed to explore the relationship between BPV and incident CKD and albuminuria. RESULTS: A total of 5700 patients were included, with a mean age of 66.4 years old. During a median of 3.29 years follow-up, 150 (2.6%) patients developed CKD and 222 (7.2%) patients developed albuminuria. Patients were divided into four groups according to the quartiles of BPV. Compared with SBPV Q1, the incidence of CKD was higher in SBPV Q2-Q4; hazard ratios and 95% confidence interval were 1.81 (1.07-3.04), 1.85 (1.10-3.12) and 1.90 (1.13-3.19), respectively. The association between incident CKD and albuminuria with DBPV was less significant than SBPV. Similar results were found when measuring BPV as ARV and SD. No interaction was detected in BP-lowering strategy and SBPV on incident CKD and albuminuria ( P  > 0.05). CONCLUSION: This study found that BPV was a risk factor for incident CKD and albuminuria in patients without CKD, especially SBPV. Although intensive BP control increased the risk of CKD, the association between SBPV and kidney function decline did not differ between the two treatment groups. REGISTRATION: URL: https://clinicaltrials.gov/ , Unique identifier: NCT01206062.

Nanoscopic Imaging of Self-Propelled Ultrasmall Catalytic Nanomotors.

Ultrasmall nanomotors (<100 nm) are highly desirable nanomachines for their size-specific advantages over their larger counterparts in applications spanning nanomedicine, directed assembly, active sensing, and environmental remediation. While there are extensive studies on motors larger than 100 nm, the design and understanding of ultrasmall nanomotors have been scant due to the lack of high-resolution imaging of their propelled motions with orientation and shape details resolved. Here, we report the imaging of the propelled motions of catalytically powered ultrasmall nanomotors─hundreds of them─at the nanometer resolution using liquid-phase transmission electron microscopy. These nanomotors are Pt nanoparticles of asymmetric shapes ("tadpoles" and "boomerangs"), which are colloidally synthesized and observed to be fueled by the catalyzed decomposition of NaBH4 in solution. Statistical analysis of the orientation and position trajectories of fueled and unfueled motors, coupled with finite element simulation, reveals that the shape asymmetry alone is sufficient to induce local chemical concentration gradient and self-diffusiophoresis to act against random Brownian motion. Our work elucidates the colloidal design and fundamental forces involved in the motions of ultrasmall nanomotors, which hold promise as active nanomachines to perform tasks in confined environments such as drug delivery and chemical sensing.

Hypoxic tumor microenvironment: Destroyer of natural killer cell function.

In recent years, immunotherapy has made remarkable progress in treating certain tumors and hematological malignancies. However, the efficacy of natural killer (NK) cells, which are an important subset of innate lymphocytes used in anticancer immunotherapy, remains limited. Hypoxia, a critical characteristic of the tumor microenvironment (TME), is involved in tumor development and resistance to radiotherapy, chemotherapy, and immunotherapy. Moreover, hypoxia contributes to the impairment of NK cell function and may be a significant factor that limits their therapeutic effects. Targeted hypoxia therapy has emerged as a promising research area for enhancing the efficacy of NK cell therapy. Therefore, understanding how the hypoxic TME influences NK cell function is crucial for improving antitumor treatment outcomes.

Colloidal synthesis of metallodielectric Janus matchsticks.

We present a gram-scale synthesis of metallodielectric Janus matchsticks, which feature a gold-coated silica sphere and a silica rod. SiO2 Janus matchsticks are synthesized in one batch by growing amine-functionalized SiO2 spheres at the end of SiO2 rods. Gold deposition on the spheres produces Au-SiO2 Janus matchsticks with an aspect ratio controlled by the rod length. The metallodielectric Janus matchsticks, produced by scalable colloidal synthesis, hold great potential as functional colloidal materials.

CG9920 is necessary for mitochondrial morphogenesis and individualization during spermatogenesis in Drosophila melanogaster.

Drosophila melanogaster is an ideal model organism for investigating spermatogenesis due to its powerful genetics, conserved genes and visible morphology of germ cells during sperm production. Our previous work revealed that ocnus (ocn) knockdown resulted in male sterility, and CG9920 was identified as a significantly downregulated protein in fly abdomen after ocn knockdown, suggesting a role of CG9920 in male reproduction. In this study, we found that CG9920 was highly expressed in fly testes. CG9920 knockdown in fly testes caused male infertility with no mature sperms in seminal vesicles. Immunofluorescence staining showed that depletion of CG9920 resulted in scattered spermatid nuclear bundles, fewer elongation cones that did not migrate to the anterior region of the testis, and almost no individualization complexes. Transmission electron microscopy revealed that CG9920 knockdown severely disrupted mitochondrial morphogenesis during spermatogenesis. Notably, we found that CG9920 might not directly interact with Ocn, but rather was inhibited by STAT92E, which itself was indirectly affected by Ocn. We propose a possible novel pathway essential for spermatogenesis in D. melanogaster, whereby Ocn indirectly induces CG9920 expression, potentially counteracting its inhibition by the JAK-STAT signaling pathway.

Comparison of 1-stage and 2-stage Managements for Common Bile Duct Stones and Gallstones (CBDS): A Retrospective Study.

OBJECTIVE: The aim of this study was to evaluate the efficacy, safety, and surgical outcomes of 2-stage management, namely preoperative endoscopic retrograde cholangiopancreatography (ERCP) + laparoscopic cholecystectomy (ERCP+LC) or LC + postoperative ERCP (LC+ERCP), as well as 1-stage management, LC + laparoscopic common bile duct exploration (LCBDE) for treating patients with gallstones and common bile duct stones (CBDS). METHODS: This retrospective study analyzed the data of 180 patients with common bile duct stones (CBDS) who were admitted to the Department of General Surgery at Tongji Hospital, Tongji University, between January 2019 and June 2021. The study included 3 groups: ERCP+LC (group 1), LC+ERCP (group 2), and LC+LCBDE (group 3), each consisting of 60 patients. Clinical metrics of the patients were collected and compared among the groups. RESULTS: Group 3 had the shortest operation duration and hospital stay compared with group 1 and group 2. In addition, group 3 had the lowest long-term postoperative complications, particularly the recurrence rate of CBDS. The total cost was also the lowest in group 3. Furthermore, patients in group 3 had the lowest postoperative amylase levels. All patients in the study achieved successful stone clearance. There were no significant differences in the conversion to other procedures rate, postoperative alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, and mortality among the three groups (P > 0.05). CONCLUSIONS: Both 1-stage management and 2-stage management are effective treatments for CBDS. The LC+LCBDE management is a safe treatment option, offering shorter hospital stays and operation duration, lower costs, and fewer complications.

Thermal-Rectified Gradient Porous Polymeric Film for Solar-Thermal Regulatory Cooling.

Solar-thermal regulation concerning thermal insulation and solar modulation is pivotal for cooling textiles and smart buildings. Nevertheless, a contradiction arises in balancing the demand to prevent external heat infiltration with the efficient dissipation of excess heat from enclosed spaces. Here, a concentration-gradient polymerization strategy is presented for fabricating a gradient porous polymeric film comprising interconnected polymeric microspheres. This method involves establishing an electric field-driven gradient distribution of charged crosslinkers in the precursor solution, followed by subsequent polymerization and freeze-drying processes. The resulting porous film exhibits a significant porosity gradient along its thickness, leading to exceptional unidirectional thermal insulation capabilities with a thermal rectification factor of 21%. The gradient porous film, with its thermal rectification properties, effectively reconciles the conflicting demands of diverse thermal conductivity for cooling unheated and spontaneously heated enclosed spaces. Consequently, the gradient porous film demonstrates remarkable enhancements in solar-thermal management, achieving temperature reductions of 3.0 and 4.1 °C for unheated and spontaneously heated enclosed spaces, respectively, compared to uniform porous films. The developed gradient-structured porous film thus holds promise for the development of thermal-rectified materials tailored to regulate solar-thermal conditions within enclosed environments.

Identification of two distinct head and neck squamous cell carcinoma subtypes based on fatty acid metabolism-related signatures: Implications for immunotherapy and chemotherapy.

The dysregulation of lipid metabolism is a critical factor in the initiation and progression of tumors. In this investigation, we aim to characterize the molecular subtypes of head and neck squamous cell carcinoma (HNSCC) based on their association with fatty acid metabolism and develop a prognostic risk model. The transcriptomic and clinical data about HNSCC were obtained from public databases. Clustering analysis was conducted on fatty acid metabolism genes (FAMG) associated with prognosis, utilizing the non-negative matrix factorization algorithm. The immune infiltration, response to immune therapy, and drug sensitivity between molecular subtypes were evaluated. Differential expression genes were identified between subtypes, and a prognostic model was constructed using Cox regression analyses. A nomogram for HNSCC was constructed and evaluated. Thirty FAMGs have been found to exhibit differential expression in HNSCC, out of which three are associated with HNSCC prognosis. By performing clustering analysis on these 3 genes, 2 distinct molecular subtypes of HNSCC were identified that exhibit significant heterogeneity in prognosis, immune landscape, and treatment response. Using a set of 7778 genes that displayed differential expression between the 2 molecular subtypes, a prognostic risk model for HNSCC was constructed comprising 11 genes. This model has the ability to stratify HNSCC patients into high-risk and low-risk groups, which exhibit significant differences in prognosis, immune infiltration, and immune therapy response. Moreover, our data suggest that this risk model is negatively correlated with B cells and most T cells, but positively correlated with macrophages, mast cells, and dendritic cells. Ultimately, we constructed a nomogram incorporating both the risk signature and radiotherapy, which has demonstrated exceptional performance in predicting prognosis for HNSCC patients. A molecular classification system and prognostic risk models were developed for HNSCC based on FAMGs. This study revealed the potential involvement of FAMGs in modulating tumor immune microenvironment and response to treatment.

Aggregation induced emission dynamic chiral europium(III) complexes with excellent circularly polarized luminescence and smart sensors.

The synthesis of dynamic chiral lanthanide complex emitters has always been difficult. Herein, we report three pairs of dynamic chiral EuIII complex emitters (R/S-Eu-R-1, R = Et/Me; R/S-Eu-Et-2) with aggregation-induced emission. In the molecular state, these EuIII complexes have almost no obvious emission, while in the aggregate state, they greatly enhance the EuIII emission through restriction of intramolecular rotation and restriction of intramolecular vibration. The asymmetry factor and the circularly polarized luminescence brightness are as high as 0.64 (5D0 → 7F1) and 2429 M-1cm-1 of R-Eu-Et-1, achieving a rare double improvement. R-Eu-Et-1/2 exhibit excellent sensing properties for low concentrations of CuII ions, and their detection limits are as low as 2.55 and 4.44 nM, respectively. Dynamic EuIII complexes are constructed by using chiral ligands with rotor structures or vibration units, an approach that opens a door for the construction of dynamic chiral luminescent materials.

The underlying neuropsychological and neural correlates of the impaired Chinese reading skills in children with attention deficit hyperactivity disorder.

Impaired basic academic skills (e.g., word recognition) are common in children with Attention Deficit Hyperactivity Disorder (ADHD). The underlying neuropsychological and neural correlates of impaired Chinese reading skills in children with ADHD have not been substantially explored. Three hundred and two children with ADHD (all medication-naïve) and 105 healthy controls underwent the Chinese language skill assessment, and 175 also underwent fMRI scans (84 ADHD and 91 controls). Between-group and mediation analyses were applied to explore the interrelationships of the diagnosis of ADHD, cognitive dysfunction, and impaired reading skills. Five ADHD-related brain functional networks, including the default mode network (DMN) and the dorsal attention network (DAN), were built using predefined regions of interest. Voxel-based group-wise comparisons were performed. The ADHD group performed worse than the control group in word-level reading ability tests, with lower scores in Chinese character recognition (CR) and word chains (WS) (all P < 0.05). With full-scale IQ and sustained attention in the mediation model, the direct effect of ADHD status on the CR score became insignificant (P = 0.066). The underlying neural correlates for the orthographic knowledge (OT) and CR differed between the ADHD and the control group. The ADHD group tended to recruit more DMN regions to maintain their reading performance, while the control group seemed to utilize more DAN regions. Children with ADHD generally presented impaired word-level reading skills, which might be caused by impaired sustained attention and lower IQ. According to the brain functional results, we infer that ADHD children might utilize a different strategy to maintain their orthographic knowledge and character recognition performance.

Efficiency and Durability of EIVOM on Acute Reconnection After Mitral Isthmus Bidirectional Block.

BACKGROUND: Reconnection after mitral isthmus (MI) block with radiofrequency ablation is common. OBJECTIVES: The aim of this study was to investigate the effects of ethanol infusion in the vein of Marshall (EIVOM) on acute reconnection after MI bidirectional block. METHODS: Patients with persistent atrial fibrillation who were scheduled to receive radiofrequency ablation for the first time were randomly assigned to the radiofrequency catheter ablation (RFCA) group (n = 44) or the EIVOM group (n = 45). The RFCA group's strategy was bilateral pulmonary vein ablation and linear ablation; in the EIVOM group, EIVOM was performed first. The primary endpoint was acute reconnection 30 minutes after MI bidirectional block. RESULTS: A total of 89 patients (average age 62.9 years; 57.3% male) were enrolled. The average duration for persistent atrial fibrillation was 2.3 years. Before observation, all patients in the EIVOM group achieved MI bidirectional block (45 of 45 [100%]), compared with 84.1% (37 of 44) in the RFCA group. After the observation, 3 cases of MI reconnection occurred in the EIVOM group and 13 cases in the RFCA group (6.7% vs 35.1%; P < 0.05). After additional ablation, the final MI block rates in the EIVOM and RFCA groups were 97.8% (44 of 45) and 72.7% (32 of 44), respectively. During a 1-year follow-up, 8 of 45 patients who underwent EIVOM had recurrent atrial fibrillation, compared with 14 of 44 in the RFCA group (17.8% vs 31.8%; P < 0.01). CONCLUSIONS: EIVOM can reduce acute reconnection after MI bidirectional block and significantly increase first-pass MI block.

Study on the Effect of Electrolytes on Processing Efficiency and Accuracy of Titanium Alloy Utilizing Laser and Shaped Tube Electrochemical Machining.

Electrochemical machining (ECM) has become more prevalent in titanium alloy processing. However, the presence of the passivation layer on the titanium alloys significantly impacts the performance of ECM. In an attempt to overcome the passivation effects, a high-temperature electrolyte or the addition of halogen ions to the electrolyte has been used. Still, it often results in compromised machining accuracy and surface roughness. This study applied laser and shaped tube electrolytic machining (Laser-STEM) for titanium alloy drilling, where the laser was guided to the machining zone via total internal reflection. The performance of Laser-STEM using different types of electrolytes was compared. Further, the effects of laser power and pulse voltage on the machining side gap, material removal rate (MRR), and surface roughness were experimentally studied while drilling small holes in titanium alloy. The results indicated that the use of passivating electrolytes improved the machining precision, while the MRR decreased with an increase in laser power during Laser-STEM. The MRR showed an increase while using aggressive electrolytes; however, at the same time, the machining precision deteriorated with the increase in laser power. Particularly, the maximum feeding rate of 6.0 mm/min for the tool electrode was achieved using NaCl solution as the electrolyte during Laser-STEM, marking a 100% increase compared to the rate without the use of a laser. Moreover, the model and equivalent circuits were also established to illustrate the material removal mechanisms of Laser-STEM in different electrolytes. Lastly, the processing of deep small holes with a diameter of 1.5 mm, a depth of 38 mm, and a surface roughness of Ra 2 µm was achieved via Laser-STEM without the presence of a recast layer and heat-affected zones. In addition, the cross-inner flow channels in the titanium alloys were effectively processed.

Healing with precision: A multi-functional hydrogel-bioactive glass dressing boosts infected wound recovery and enhances neurogenesis in the wound bed.

Chronic skin wounds, especially infected ones, pose a significant clinical challenge due to their increasing incidence and poor outcomes. The deteriorative microenvironment in such wounds, characterized by reduced extracellular matrix, impaired angiogenesis, insufficient neurogenesis, and persistent bacterial infection, has prompted the exploration of novel therapeutic strategies. In this study, we developed an injectable multifunctional hydrogel (GEL/BG@Cu + Mg) incorporating Gelatin-Tannic acid/ N-hydroxysuccinimide functionalized polyethylene glycol and Bioactive glass doped with copper and magnesium ions to accelerate the healing of infected wounds. The GEL/BG@Cu + Mg hydrogel composite demonstrates good biocompatibility, degradability, and rapid formation of a protective barrier to stop bleeding. Synergistic bactericidal effects are achieved through the photothermal properties of BG@Cu + Mg and sustained copper ions release, with the latter further promoting angiogenesis. Furthermore, the hydrogel enhances neurogenesis by stimulating axons and Schwann cells in the wound bed through the beneficial effects of magnesium ions. Our results demonstrate that the designed novel multifunctional hydrogel holds tremendous promise for treating infected wounds and allowing regenerative neurogenesis at the wound site, which provides a viable alternative for further improving clinical outcomes.

Molecular subtype identification of cerebral ischemic stroke based on ferroptosis-related genes.

Cerebral ischemic stroke (CIS) has the characteristics of a high incidence, disability, and mortality rate. Here, we aimed to explore the potential pathogenic mechanisms of ferroptosis-related genes (FRGs) in CIS. Three microarray datasets from the Gene Expression Omnibus (GEO) database were utilized to analyze differentially expressed genes (DEGs) between CIS and normal controls. FRGs were obtained from a literature report and the FerrDb database. Weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network were used to screen hub genes. The receiver operating characteristic (ROC) curve was adopted to evaluate the diagnostic value of key genes in CIS, followed by analysis of immune microenvironment, transcription factor (TF) regulatory network, drug prediction, and molecular docking. In total, 128 CIS samples were divided into 2 subgroups after clustering analysis. Compared with cluster A, 1560 DEGs were identified in cluster B. After the construction of the WGCNA and PPI network, 5 hub genes, including MAPK3, WAS, DNAJC5, PRKCD, and GRB2, were identified for CIS. Interestingly, MAPK3 was a FRG that differentially expressed between cluster A and cluster B. The expression levels of 5 hub genes were all specifically highly in cluster A subtype. It is noted that neutrophils were the most positively correlated with all 5 real hub genes. PRKCD was one of the target genes of FASUDIL. In conclusion, five real hub genes were identified as potential diagnostic markers, which can distinguish the two subtypes well.

Association between per- and poly-fluoroalkyl substances and nonalcoholic fatty liver disease: A nested case-control study in northwest China.

Per- and poly-fluoroalkyl substances (PFAS) have been reported to have hepatotoxic effects. However, it is unclear whether they are linked to non-alcoholic fatty liver disease (NAFLD). This nested case-control study focused on the epidemiological links between PFAS and the prevalence of NAFLD. We selected 476 new cases of NAFLD and 952 age- and sex-matched controls from the Jinchang cohort population between 2014 and 2019. Serum concentrations of PFAS were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Only PFAS with a detection rate of ≥90 % were included for analysis, which included PFPeA, PFOA, PFNA, PFHxS, PFOS, and 9Cl-PF3ONS. The relationship between single and co-exposure to PFAS and the occurrence of NAFLD was evaluated using conditional logistic regression, Quantile g-computation (QgC), and Bayesian kernel machine regression (BKMR) model. Logistic regression indicated that PFPeA, PFOA, and 9Cl-PF3ONS were positive correlation with the incidence of NAFLD after adjusting for confounders, with odds ratios (OR) and 95 % confidence interval (CI) of 3.13 (95 % CI: 2.53, 3.86), 1.39 (95 % CI: 1.12, 1.73), and 1.41 (95 % CI: 1.20, 1.66), respectively. PFNA, PFHxS, and PFOS were nonlinearly and negatively associated with the incidence of NAFLD, with OR (95 % CI) of 0.53 (0.46, 0.62), 0.83 (0.73, 0.95), and 0.52 (0.44, 0.61), respectively. QgC showed a significant joint effect of PFAS mixture on NAFLD onset (OR: 1.52, 95 % CI: 1.24, 1.88). BKMR showed a weak positive trend between PFAS mixtures and NAFLD incidence. Positive correlations were primarily driven by PFPeA and 9Cl-PF3ONS, while negative correlations were mainly influenced by PFNA and PFOS. The BKMR model also suggested that there was an interaction between PFOS and PFNA and other four PFAS compounds. In conclusion, our findings suggest that individual and co-exposure to PFAS is associated with a risk of NAFLD onset.