PLCL/SF/NGF nerve conduit loaded with RGD-TA-PPY hydrogel promotes regeneration of sciatic nerve defects in rats through PI3K/AKT signalling pathways.

Peripheral nerve defect are common clinical problem caused by trauma or other diseases, often leading to the loss of sensory and motor function in patients. Autologous nerve transplantation has been the gold standard for repairing peripheral nerve defects, but its clinical application is limited due to insufficient donor tissue. In recent years, the application of tissue engineering methods to synthesize nerve conduits for treating peripheral nerve defect has become a current research focus. This study introduces a novel approach for treating peripheral nerve defects using a tissue-engineered PLCL/SF/NGF@TA-PPy-RGD conduit. The conduit was fabricated by combining electrospun PLCL/SF with an NGF-loaded conductive TA-PPy-RGD gel. The gel, synthesized from RGD-modified tannic acid (TA) and polypyrrole (PPy), provides growth anchor points for nerve cells. In vitro results showed that this hybrid conduit could enhance PC12 cell proliferation, migration, and reduce apoptosis under oxidative stress. Furthermore, the conduit activated the PI3K/AKT signalling pathway in PC12 cells. In a rat model of sciatic nerve defect, the PLCL/SF/NGF@TA-PPy-RGD conduit significantly improved motor function, gastrocnemius muscle function, and myelin sheath axon thickness, comparable to autologous nerve transplantation. It also promoted angiogenesis around the nerve defect. This study suggests that PLCL/SF/NGF@TA-PPy-RGD conduits provide a conducive environment for nerve regeneration, offering a new strategy for peripheral nerve defect treatment, this study provided theoretical basis and new strategies for the research and treatment of peripheral nerve defect.

LncRNA LOC730101 Promotes Darolutamide Resistance in Prostate Cancer by Suppressing miR-1-3p.

Antiandrogen is part of the standard-of-care treatment option for metastatic prostate cancer. However, prostate cancers frequently relapse, and the underlying resistance mechanism remains incompletely understood. This study seeks to investigate whether long non-coding RNAs (lncRNAs) contribute to the resistance against the latest antiandrogen drug, darolutamide. Our RNA sequencing analysis revealed significant overexpression of LOC730101 in darolutamide-resistant cancer cells compared to the parental cells. Elevated LOC730101 levels were also observed in clinical samples of metastatic castration-resistant prostate cancer (CRPC) compared to primary prostate cancer samples. Silencing LOC730101 with siRNA significantly impaired the growth of darolutamide-resistant cells. Additional RNA sequencing analysis identified a set of genes regulated by LOC730101, including key players in the cell cycle regulatory pathway. We further demonstrated that LOC730101 promotes darolutamide resistance by competitively inhibiting microRNA miR-1-3p. Moreover, by Hi-C sequencing, we found that LOC730101 is located in a topologically associating domain (TAD) that undergoes specific gene induction in darolutamide-resistant cells. Collectively, our study demonstrates the crucial role of the lncRNA LOC730101 in darolutamide resistance and its potential as a target for overcoming antiandrogen resistance in CRPC.

Tear Fluid Progranulin as a Noninvasive Biomarker for the Monitoring of Corneal Innervation Changes in Patients With Type 2 Diabetes Mellitus.

Purpose: This study aimed to investigate the expression levels of progranulin (PGRN) in the tears of patients with diabetic retinopathy (DR) versus healthy controls. Additionally, we sought to explore the correlation between PGRN levels and the severity of ocular surface complications in patients with diabetes. Methods: In this prospective, single-visit, cross-sectional study, patients with DR (n = 48) and age-matched healthy controls (n = 22) were included and underwent dry eye examinations. Tear fluid was collected, and its components were analyzed using the Luminex assay. The subbasal nerve plexus of all participants was evaluated by in vivo confocal microscopy. Results: Patients with DR exhibited more severe dry eye symptoms, along with a reduction in nerve fiber density, length, and branch density within the subbasal nerve plexus, accompanied by an increase in the number of dendritic cells. Tear PGRN levels were also significantly lower in patients with diabetes than in normal controls, and the levels of some inflammatory factors (TNF-α, IL-6, and MMP-9) were higher in patients with DR. Remarkably, the PGRN level significantly correlated with nerve fiber density (R = 0.48, P < 0.001), nerve fiber length (R = 0.65, P < 0.001), and nerve branch density (R = 0.69, P < 0.001). Conclusions: Tear PGRN levels might reflect morphological changes in the corneal nerve plexus under diabetic conditions, suggesting that PGRN itself is a reliable indicator for predicting the advancement of neurotrophic keratopathy in patients with diabetes. Translational Relevance: PGRN insufficiency on the ocular surface under diabetic conditions was found to be closely associated with nerve impairment, providing a novel perspective to discover the pathogenesis of diabetic complications, which could help in developing innovative therapeutic strategies.

Parental hesitancy about COVID-19, influenza, HPV, and other childhood vaccines.

BACKGROUND: Some public health professionals have expressed concern that the COVID-19 pandemic has increased vaccine hesitancy about routine childhood vaccines; however, the differential prevalence of vaccine hesitancy about specific vaccines has not been measured. METHODS: Data from the National Immunization Survey-Child COVID-19 Module (NIS-CCM) were analyzed to assess the proportion of children ages 6 months-17 years who have a parent with hesitancy about: COVID-19, influenza, human papillomavirus (HPV) (for children ≥ 9 years) vaccines, and "all other childhood shots." Interviews from October 2022 through April 2023 were analyzed. RESULTS: The percentage of children with a vaccine-hesitant parent varied by vaccine. 55.9% of children had a parent hesitant about COVID-19 vaccine, 30.9% hesitant about influenza vaccine, 30.1% hesitant about HPV vaccine, and 12.2% had a parent hesitant about other vaccines such as measles, polio, and tetanus. CONCLUSION: The study findings suggest that differential interventions and communications to parents be used to educate about COVID-19, influenza, HPV, and routine childhood vaccinations because the hesitancy levels differ widely.

Multi-mode resonance of bound states in the continuum in dielectric metasurfaces.

Bound states in the continuum (BIC) represent distinct non-radiative states endowed with infinite lifetime and vanishing resonance linewidth. Introducing asymmetric perturbation to the system can convert true BICs into high quality leaky modes which is useful in many photonic applications. Previously, such perturbation and resonance of interest is only limited to a single factor. However, different perturbations by unit cell gap, geometry and rotation angle result distinctive resonance modes. The combination of two perturbation factors can excite multi-mode resonance contributed from each asymmetric factor which coexist simultaneously; thus, the number of reflectance peaks can be controlled. In addition, we have carefully analyzed the electric field variations under different perturbation factors, followed by a multipolar decomposition of resonances to reveal underlying mechanisms of distinct resonance modes. Through simulations, we find that the introduction of multiple asymmetric perturbations also influences the metasurface sensitivity in refractive index sensing and compare the performance of different resonance modes. These observations provide structural design insights for achieving high quality resonance with multiple modes and ultra-sensitive sensing.

Associations between sexual identity stigma and positive sexual identity, and depression among men who have sex with men in China: A mediation analysis using structural equation modelling.

PURPOSE: High levels of depression are common among men who have sex with men (MSM) in China, and there is limited research on the relationship between MSM stigma and depression. Guided by the psychological mediation framework, to explore the relationship between stigma and depression among MSM and how positive sexual identity plays a role in it, we tested this model whether: 1) enacted MSM stigma, perceived MSM stigma, and positive sexual identity are associated with depression; 2) their effects on depression are mediated through resilient coping and social support; and 3) perceived MSM stigma is a mediator of the effects of enacted MSM stigma and positive sexual identity on depression. METHODS: We conducted mediation analyses using structural equation modeling (SEM) on data from a cross-sectional survey conducted among 1014 MSM recruited using a non-probability sampling method in December 2022. The data passed general analyses such as normality and correlation, which allowed for modeling. The final SEM fit metrics indicated that the model was acceptable. RESULTS: Structural equation modeling results showed that enacted stigma directly and positively affected depressive symptoms (ß = 0.558, 95 % confidence interval = 0.457 ～ 0.644, P < 0.001). Perceived stigma had a positive effect on depressive symptoms (ß = 0.114, 95 %CI = 0.036 ～ 0.200, P = 0.002). Positive identity had a positive effect on depressive symptoms (ß = 0.086, 95 %CI = 0.016 ～ 0.162, P = 0.013). In addition, the results of mediation effect analysis showed that the indirect effect of enacted stigma on the effect of depression through social support was (ß = 0.040, 95 %CI = 0.003 ∼ 0.017, P = 0.049); The indirect effect of perceived stigma on the effect of depression through resilient coping was (ß = -0.015, 95 %CI = -0.034 ∼ -0.002, P = 0.056); The indirect effects of positive sexual identity on the effect of depression through resilient coping and social support were (ß = -0.025, 95 %CI = -0.056 ∼ -0.002, P = 0.052) and (ß = -0.056, 95 %CI = -0.101 ∼ -0.023, P = 0.005). CONCLUSION: Resilient coping and social support mediated the relationship between stigma and depression, and both were influenced by positive identity. This study reveals that enhancing coping and social support may reduce the impact of stigma on depressive symptoms, both of which are potential targets for interventions for MSM. Guiding MSM to develop a positive sexual identity is conducive to reducing the prevalence of depressive symptoms among MSM.

[A prospective cohort study of association between early childhood body mass index trajectories and the risk of overweight].

OBJECTIVE: To compare the association between body mass index (BMI) trajectories determined by different methods and the risk of overweight in early childhood in a prospective cohort study, and to identify children with higher risk of obesity during critical growth windows of early childhood. METHODS: A total of 1 330 children from Peking University Birth Cohort in Tongzhou (PKUBC-T) were included in this study. The children were followed up at birth, 1, 3, 6, 9, 12, 18, and 24 months and 3 years of age to obtain their height/length and weight data, and calculate BMI Z-score. Latent class growth mixture modeling (GMM) and longitudinal data-based k-means clustering algorithm (KML) were used to determine the grouping of early childhood BMI trajectories from birth to 24 mouths. Linear regression was used to compare the association between early childhood BMI trajectories determined by different methods and BMI Z-score at 3 years of age. The predictive performance of early childhood BMI trajectories determined by different methods in predicting the risk of overweight (BMI Z-score > 1) at 3 years was compared using the average area under the curve (AUC) of 5-fold cross-validation in Logistic regression models. RESULTS: In the study population included in this research, the three-category trajectories determined using GMM were classified as low, medium, and high, accounting for 39.7%, 54.1%, and 6.2% of the participants, respectively. The two-category trajectories determined using the KML method were classified as low and high, representing 50. 3% and 49. 7% of the participants, respectively. The three-category trajectories determined using the KML method were classified as low, medium, and high, accounting for 31.1%, 47.4%, and 21.5% of the participants, respectively. There were certain differences in the growth patterns reflected by the early childhood BMI trajectories determined using different methods. Linear regression analysis found that after adjusting for maternal ethnicity, educational level, delivery mode, parity, maternal age at delivery, gestational week at delivery, children' s gender, and breastfeeding at 1 month of age, the association between the high trajectory group in the three-category trajectories determined by the KML method (manifested by a slightly higher BMI at birth, followed by rapid growth during infancy and a stable-high BMI until 24 months) and BMI Z-scores at 3 years was the strongest. Logistic regression analysis revealed that the three-category trajectory grouping determined by the KML method had the best predictive performance for the risk of overweight at 3 years. The results were basically consistent after additional adjustment for the high bound score of the child' s diet balanced index, average daily physical activity time, and screen time. CONCLUSION: This study used different methods to identify early childhood BMI trajectories with varying characteristics, and found that the high trajectory group determined by the KML method was better able to identify children with a higher risk of overweight in early childhood. This provides scientific evidence for selecting appropriate methods to define early childhood BMI trajectories.

Assessment Methods and Intervention Strategies for Cleft-Related Lateral Misarticulation in Chinese-Speaking Children.

The aim of this study was to analyze the characteristics and error speech features of cleft-related lateral misarticulation and provide a basis for clinical evaluation and rational intervention. Participants who were diagnosed with lateral misarticulation after cleft palate repairment were 126 children aged 4, 6 to 16, and 11, and they had complete palatopharyngeal closure, no abnormalities in their speech organs and occlusion, and no hearing or intellectual impairments. The Chinese standard pronunciation clarity word list, the American KAY CSL4500, the Beijing Yangchen YF-16 computer speech analysis workstation, soundproof rooms, Wechsler scales of intelligence-fourth edition, and audiometers were used to evaluate the cleft-related lateral misarticulation. Statistical analysis was performed on the age, gender, error rate, corner of the mouth deviation direction, comorbidity, duration of intervention, period of treatment, and therapeutic effect of concentrated or normal intervention group in different patients. Our results showed that 2 to 3 straight stripes were visible at the onset of consonants /ti:/ /t'i:/, and 3 clear straight lines were visible in /tʂ/, indicating that the lateralized sound had 2 or 3 bursts and lasted for 1 to 2 ms. The onset age of lateralized sound was mostly below 12 years old. Chinese lateralized sound mainly occurred in vowel /i:/, and the occurrence rate of consonants with tongue surface /tɕ]/ /tɕ'/ /ɕ/ was the highest. In addition, the corner of the mouth deviation was also an indicator of lateralization sound, and other types of speech disorders mostly accompanied it. There was a significant difference in the improvement of speech clarity between the concentrated intervention group and the normal group before and after treatment. The 2 groups' average duration and course of treatment were not significantly different. Still, the period of concentrated intervention was shortened considerably, and the speech clarity of both groups of children after treatment exceeded 96%, reaching a normal level.

Liver X Receptor Ligand GAC0001E5 Downregulates Antioxidant Capacity and ERBB2/HER2 Expression in HER2-Positive Breast Cancer Cells.

The HER2-positive subtype accounts for approximately one-fifth of all breast cancers. Insensitivity and development of acquired resistance to targeted therapies in some patients contribute to their poor prognosis. HER2 overexpression is associated with metabolic reprogramming, facilitating cancer cell growth and survival. Novel liver X receptor (LXR) ligand GAC0001E5 (1E5) has been shown to inhibit cancer cell proliferation by disrupting glutaminolysis and inducing oxidative stress. In this study, HER2-positive breast cancer cells were treated with 1E5 to determine their potential inhibitory effects and mechanisms of action in HER2-positive breast cancers. Similar to previous observations in other cancer types, 1E5 treatments inhibited LXR activity, expression, and cancer cell proliferation. Expression of fatty acid synthesis genes, including fatty acid synthase (FASN), was downregulated following 1E5 treatment, and results from co-treatment experiments with an FASN inhibitor suggest that the same pathway is targeted by 1E5. Treatments with 1E5 disrupted glutaminolysis and resulted in increased oxidative stress. Strikingly, HER2 transcript and protein levels were both significantly downregulated by 1E5. Taken together, these findings indicate the therapeutic potential of targeting HER2 overexpression and associated metabolic reprogramming via the modulation of LXR in HER2-positive breast cancers.

Medication Usage Record-Based Predictive Modeling of Neurodevelopmental Abnormality in Infants under One Year: A Prospective Birth Cohort Study.

Early identification of children with neurodevelopmental abnormality is a major challenge, which is crucial for improving symptoms and preventing further decline in children with neurodevelopmental abnormality. This study focuses on developing a predictive model with maternal sociodemographic, behavioral, and medication-usage information during pregnancy to identify infants with abnormal neurodevelopment before the age of one. In addition, an interpretable machine-learning approach was utilized to assess the importance of the variables in the model. In this study, artificial neural network models were developed for the neurodevelopment of five areas of infants during the first year of life and achieved good predictive efficacy in the areas of fine motor and problem solving, with median AUC = 0.670 (IQR: 0.594, 0.764) and median AUC = 0.643 (IQR: 0.550, 0.731), respectively. The final model for neurodevelopmental abnormalities in any energy region of one-year-old children also achieved good prediction performance. The sensitivity is 0.700 (IQR: 0.597, 0.797), the AUC is 0.821 (IQR: 0.716, 0.833), the accuracy is 0.721 (IQR: 0.696, 0.739), and the specificity is 0.742 (IQR: 0.680, 0.748). In addition, interpretable machine-learning methods suggest that maternal exposure to drugs such as acetaminophen, ferrous succinate, and midazolam during pregnancy affects the development of specific areas of the offspring during the first year of life. This study established predictive models of neurodevelopmental abnormality in infants under one year and underscored the prediction value of medication exposure during pregnancy for the neurodevelopmental outcomes of the offspring.

Toward More Selective Antibiotic Inhibitors: A Structural View of the Complexed Binding Pocket of E. coli Peptide Deformylase.

Peptide deformylase (PDF) is involved in bacterial protein maturation processes. Originating from the interest in a new antibiotic, tremendous effort was put into the refinement of PDF inhibitors (PDFIs) and their selectivity. We obtained a full NMR backbone assignment the emergent additional protein backbone resonances of ecPDF 1-147 in complex with 2-(5-bromo-1H-indol-3-yl)-N-hydroxyacetamide (2), a potential new structural scaffold for more selective PDFIs. We also determined the complex crystal structures of E. coli PDF (ecPDF fl) and 2. Our structure suggests an alternative ligand conformation within the protein, a possible starting point for further selectivity optimization. The orientation of the second ligand conformation in the crystal structure points toward a small region of the S1' pocket, which differs between bacterial PDFs and human PDF. Moreover, we analyzed the binding mode of 2 via NMR TITAN line shape analysis, revealing an induced fit mechanism.

Super High Contrast USPIO-Enhanced Cerebrovascular Angiography Using Ultrashort Time-to-Echo MRI.

Background: Ferumoxytol (Ferahame, AMAG Pharmaceuticals, Waltham, MA) is increasingly used off-label as an MR contrast agent due to its relaxivity and safety profiles. However, its potent T2∗ relaxivity limits achievable T1-weighted positive contrast and leads to artifacts in standard MRI protocols. Optimization of protocols for ferumoxytol deployment is necessary to realize its potential. Methods: We present first-in-human clinical results of the Quantitative Ultrashort Time-to-Echo Contrast Enhanced (QUTE-CE) MRA technique using the superparamagnetic iron oxide nanoparticle agent ferumoxytol for vascular imaging of the head/brain in 15 subjects at 3.0T. The QUTE-CE MRA method was implemented on a 3T scanner using a stack-of-spirals 3D Ultrashort Time-to-Echo sequence. Time-of-flight MRA and standard TE T1-weighted (T1w) images were also collected. For comparison, gadolinium-enhanced blood pool phase images were obtained retrospectively from clinical practice. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and intraluminal signal heterogeneity (ISH) were assessed and compared across approaches with Welch's two-sided t-test. Results: Fifteen volunteers (54 ± 17 years old, 9 women) participated. QUTE-CE MRA provided high-contrast snapshots of the arterial and venous networks with lower intraluminal heterogeneity. QUTE-CE demonstrated significantly higher SNR (1707 ± 226), blood-tissue CNR (1447 ± 189), and lower ISH (0.091 ± 0.031) compared to ferumoxytol T1-weighted (551 ± 171; 319 ± 144; 0.186 ± 0.066, respectively) and time-of-flight (343 ± 104; 269 ± 82; 0.190 ± 0.016, respectively), with p < 0.001 in each comparison. The high CNR increased the depth of vessel visualization. Vessel lumina were captured with lower heterogeneity. Conclusion: Quantitative Ultrashort Time-to-Echo Contrast-Enhanced MR angiography provides approximately 5-fold superior contrast with fewer artifacts compared to other contrast-enhanced vascular imaging techniques using ferumoxytol or gadolinium, and to noncontrast time-of-flight MR angiography, for clinical vascular imaging. This trial is registered with NCT03266848.

Exploring relevant factors of cognitive impairment in the elderly Chinese population using Lasso regression and Bayesian networks.

Older adults are highly susceptible to developing cognitive impairment(CI). Various factors contribute to the prevalence of CI, but the potential relationships among these factors remain unclear. This study aims to explore the relevant factors associated with CI in Chinese older adults and analyze the potential relationships between CI and these factors.We analyzed the data on 6886 older adults aged≥60 from the China Health and Retirement Longitudinal Study (CHARLS) 2018. Lasso regression was initially used to screening variables. Bayesian Networks(BNs) were used to identify the correlates of CI and potential associations between factors. After screening with Lasso regression, 11 variables were finally included in the BNs. The BNs, by establishing a complex network relationship, revealed that age, education, and indoor air pollution were the direct correlates affecting the occurrence of CI in older adults. It also indicated that marital status indirectly influenced CI through age, and residence indirectly linked to CI through two pathways: indoor air pollution and education.Our findings underscore the effectiveness of BNs in unveiling the intricate network linkages among CI and its associated factors, holding promising applications. It can serve as a reference for public health departments to address the prevention of CI in the elderly.

A Time-Consistency Curriculum for Learning From Instance-Dependent Noisy Labels.

Many machine learning algorithms are known to be fragile on simple instance-independent noisy labels. However, noisy labels in real-world data are more devastating since they are produced by more complicated mechanisms in an instance-dependent manner. In this paper, we target this practical challenge of Instance-Dependent Noisy Labels by jointly training (1) a model reversely engineering the noise generating mechanism, which produces an instance-dependent mapping between the clean label posterior and the observed noisy label and (2) a robust classifier that produces clean label posteriors. Compared to previous methods, the former model is novel and enables end-to-end learning of the latter directly from noisy labels. An extensive empirical study indicates that the time-consistency of data is critical to the success of training both models and motivates us to develop a curriculum selecting training data based on their dynamics on the two models' outputs over the course of training. We show that the curriculum-selected data provide both clean labels and high-quality input-output pairs for training the two models. Therefore, it leads to promising and robust classification performance even in notably challenging settings of instance-dependent noisy labels where many SoTA methods could easily fail. Extensive experimental comparisons and ablation studies further demonstrate the advantages and significance of the time-consistency curriculum in learning from instance-dependent noisy labels on multiple benchmark datasets.

False Correlation Reduction for Offline Reinforcement Learning.

Offline reinforcement learning (RL) harnesses the power of massive datasets for resolving sequential decision problems. Most existing papers only discuss defending against out-of-distribution (OOD) actions while we investigate a broader issue, the false correlations between epistemic uncertainty and decision-making, an essential factor that causes suboptimality. In this paper, we propose falSe COrrelation REduction (SCORE) for offline RL, a practically effective and theoretically provable algorithm. We empirically show that SCORE achieves the SoTA performance with 3.1x acceleration on various tasks in a standard benchmark (D4RL). The proposed algorithm introduces an annealing behavior cloning regularizer to help produce a high-quality estimation of uncertainty which is critical for eliminating false correlations from suboptimality. Theoretically, we justify the rationality of the proposed method and prove its convergence to the optimal policy with a sublinear rate under mild assumptions.

Structural Insights into Antibacterial Payload Release from Gold Nanoparticles Bound to E. coli Peptide Deformylase.

The lack of new antibiotics and the rapidly rising number of pathogens resistant to antibiotics pose a serious problem to mankind. In bacteria, the cell membrane provides the first line of defence to antibiotics by preventing them from reaching their molecular target. To overcome this entrance barrier, it has been suggested[1] that small Gold-Nanoparticles (AuNP) could possibly function as drug delivery systems for antibiotic ligands. Using actinonin-based ligands, we provide here proof-of-principle of AuNP functionalisation, the capability to bind and inhibit the target protein of the ligand, and the possibility to selectively release the antimicrobial payload. To this end, we successfully synthesised AuNP coated with thio-functionalised actinonin and a derivative. Interactions between 15N-enriched His-peptide deformylase 1-147 from E. coli (His-ecPDF 1-147) and compound-coated AuNP were investigated via 2D 1H-15N-HSQC NMR spectra proving the direct binding to His-ecPDF 1-147. More importantly by adding dithiothreitol (DTT), we show that the derivative is successfully released from AuNPs while still bound to His-ecPDF 1-147. Our findings indicate that AuNP-conjugated ligands can address and bind intracellular target proteins. The system introduced here presents a new delivery platform for antibiotics and allows for the easy optimisation of ligand coated AuNPs.

Super-tough poly(lactic acid)/silicone rubber thermoplastic vulcanizates: The organic and inorganic synergistic interfacial compatibilization.

Polymer modification using silicone rubber represents a promising avenue for enhancing physico-mechanical properties. However, achieving optimal performance through direct blending is hindered by the poor interface compatibility between silicone rubber and the matrix. In this study, we prepared super-tough thermoplastic vulcanizates (TPVs) of polylactic acid/silicone rubber through dynamic vulcanization with PLA, methyl vinyl silicone rubber (MVQ), glycidyl methacrylate grafted MVQ (MVQ-g-GMA), and fumed silica nanoparticles (SiO2). The impact of the SiO2 addition in MVQ on the morphology, mechanical properties, crystallization, and thermal properties of the TPVs was investigated. The results showed that MVQ-g-GMA and SiO2 exhibited a synergistic compatibilization effect significantly improving the interfacial adhesion between PLA and MVQ. Therefore, the impact and tensile strength of the TPVs increased from 8.0 kJ/m2 and 22.2 MPa to 62.6 kJ/m2 and 36.7 MPa, respectively. Moreover, the TPVs also presented good low-temperature toughness with a maximum impact strength of 40.4 kJ/m2 at -20 °C. Additionally, improvements in thermal stability and crystallization rate were also observed. Overall, combining organic and inorganic synergistic compatibilization is a feasible and effective method to fabricate outstanding low-temperature toughness to PLA.

Monkeypox Virus Crosstalk with HIV: An Integrated Skin Transcriptome and Machine Learning Study.

The emergence of the monkeypox virus (MPXV) outbreak presents a formidable challenge to human health. Emerging evidence suggests that individuals with HIV have been disproportionately affected by MPXV, with adverse clinical outcomes and higher mortality rates. However, the shared molecular mechanisms underlying MPXV and HIV remain elusive. We identified differentially expressed genes (DEGs) from two public data sets, GSE219036 and GSE184320, and extracted common DEGs between MPXV and HIV. We further performed gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interactions (PPI), candidate drug assessment, and immune correlation of hub genes analysis. We validated the key biomarkers using multiple machine learning (ML) methods including random forest (RF), t-distributed stochastic neighbor embedding (tSNE), and uniform manifold approximation and projection (UMAP). A total of 59 common DEGs were identified between MPXV and HIV. Our functional analysis highlighted multiple pathways, including the ERK cascade, NF-κB signaling, and various immune responses, playing a collaborative role in the progression of both diseases. The PPI and gene co-expression networks were constructed, and five key genes with significant immune correlations were identified and validated by multiple ML models, including SPRED1, SPHK1, ATF3, AKT3, and AKT1S1. Our study emphasizes the common pathogenesis of HIV and MPXV and highlights the pivotal genes and shared pathways, providing new opportunities for evidence-based management strategies in HIV patients co-infected with MPXV.

Genetic evidence implicating circulating lipids and lipid drug targets in pterygium.

There is limited knowledge about the impact of circulating lipids and lipid-modifying drugs on pterygium development, with conflicting results reported. Our study aimed to address these questions by applying the Mendelian randomization (MR) approach. A two-step MR model was developed. In the first step, bidirectional two-sample MR was employed to establish the causal relationship between circulating lipids and pterygium risk. In the second step, drug-target MR analysis was conducted to assess the causal effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) inhibitors on pterygium outcomes. Genetically predicted low-density lipoprotein cholesterol (LDL-c) levels were found to be significantly associated with an increased risk of pterygium (Inverse variance weighted [IVW] odds ratio [OR] = 2.227; P = 1.53 × 10-4). Similarly, higher total cholesterol (TC) levels exhibited a suggestive association with greater susceptibility to pterygium (IVW OR = 1.806; P = 1.70 × 10-3). Through drug-target MR, a positive causal association was noted between HMGCR-mediated LDL-c levels and pterygium (IVW OR = 6.999; P = 0.016), suggesting that statins may be effective in reducing pterygium risk. The present findings suggest that circulating TC and LDL-c are risk factors for pterygium. Additionally, the results indicate that HMGCR inhibitors, which lower LDL-c levels, have a potential protective effect on pterygium outcomes. Further research is warranted to elucidate the underlying mechanisms involved in pterygium pathogenesis, with a particular focus on cholesterol metabolism.

A Study of the Relationship between Men Who Have Sex with Men Stigma and Depression: A Moderated Mediation Model.

(1) Background: Men who have sex with men (MSM) have a high prevalence of depression due to stigma. However, whether resilience and social support play a moderating role in the effects of stigma on depression remains to be tested. This study constructed a moderated mediation model to explore the mediating role of perceived stigma in the relationship between enacted stigma and depression and whether this relationship is moderated by social support. (2) Methods: MSM were recruited during November-December 2022 using a non-probability sampling method, and a total of 1091 participants were included. Enacted stigma, perceived stigma, resilience, social support, and depressive symptoms were measured. Mediation and moderated mediation models were used to analyze the relationships between these variables. (3) Results: Moderated mediation analyses show that enacted stigma indirectly affects depression through perceived stigma (ß = 0.315, 95% confidence interval = 0.221 to 0.421). Social support had a positive moderating effect between enacted stigma and depressive symptoms (ß = 0.194, p < 0.001) and a negative moderating effect between perceived stigma and depressive symptoms (ß = -0.188, p < 0.001). (4) Resilience and perceived stigma mediated the relationship between enacted stigma and depression, and the relationship between enacted stigma, perceived stigma, and depression was moderated by social support. Reducing stigma while increasing social support has the potential to alleviate depressive symptoms among Chinese MSM.