Enhancing melanoma therapy by modulating the immunosuppressive microenvironment with an MMP-2 sensitive and nHA/GNE co-encapsulated hydrogel.

The immunosuppressive tumor microenvironment, such as lactic acid and matrix metalloproteinases (MMPs) overexpression, has been well confirmed to be adverse for tumor therapy. In current study, a tumor microenvironment modulatory hydrogel was successfully developed to treat melanoma by taking advantage of the synergistic effects of nano-hydroxyapatite (nHA) with well-documented selective anti-tumor action, lactate dehydrogenase A inhibitor (R)-GNE-140 (GNE), and matrix metalloproteinase-2 (MMP-2) sensitive peptide. The hydrogel was acquired by the reaction of 4-arm-polyethylene glycol-maleic anhydride (4-arm-PEG-MAL) and MMP-2 sensitive peptide (CC-14), in which nHA and GNE were co-encapsulated physically. The in vitro degradation tests confirmed the accelerated release of nHA and GNE from the hydrogel under less-acidic (pH 6.8) and MMP-2 containing conditions compared to those neutral or without MMP-2 conditions, demonstrating the pH and MMP-2 responsive properties of as-prepared hydrogel. Findings from in vitro cell experiments revealed that the hydrogel could stop the proliferation of melanoma cells by stacking cell cycle via lactic acid metabolic dysregulation and boosting cell apoptosis via nHA direct killing effect. Moreover, after hydrogel treatment, the rate of migration and aggressiveness of melanoma cells both reduced significantly. An in vivo anti-melanoma study showed that the hydrogel could inhibit tumor growth significantly and result in more CD8+ T cells and antigen-presenting cells but less Treg cells infiltration, ultimately leading to an enhanced therapeutic efficacy. As thus, the fabricated hydrogel demonstrated great promise for treating melanoma and could be a new potent strategy for efficient melanoma therapy. STATEMENT OF SIGNIFICANCE: Nano-hydroxyapatite (nHA) has the capability of selectively killing cancer cells. The study reported a tumor microenvironment (TME) modulatory hydrogel with the goal of enhancing melanoma therapy efficacy by combining nHA administration with immunosuppressive microenvironment modulation. The hydrogel demonstrated pH and MMP-2 sensitivity. Hence, controlled release of nHA and lactate dehydrogenase A inhibitor (GNE) could be observed, and in situ MMP-2 consumption at the tumor site occurred. The hydrogel effectively inhibited the growth of melanoma cells. Furthermore, hydrogel increased the production of CD8+ T cells and antigen-presenting cells while decreasing the infiltration of Treg cells at the tumor site. This could transform the initial "cold" tumor into a "hot" tumor, ultimately resulting in an enhanced therapeutic effect.

Hsa_circ_0000825 promotes the progression of laryngeal squamous cell carcinoma by sponging miR-766 and interacting with ELAVL1.

Emerging evidence suggests that circular RNAs (circRNAs) are involved in the regulation of tumourigenesis and progression of a variety of malignant tumours. In this study, we aimed to identify laryngeal squamous cell carcinoma (LSCC)-specific circRNAs and explore their biological functions and underlying molecular mechanisms. Employing microarray and qRT-PCR, hsa_circ_0000825 was found to be significantly increased in LSCC tissues versus para-cancerous tissues. High hsa_circ_0000825 expression was positively associated with advanced clinical stages, lymph node metastasis, and poor survival. Furthermore, the overexpression of hsa_circ_0000825 in TU177 and AMC-HN-8 cells promoted cell proliferation. Transwell assays showed enhanced migration and invasion of TU177 and AMC-HN-8 cells upon overexpression of hsa_circ_0000825. Conversely, the knockdown of hsa_circ_0000825 had the opposite effect. Xenograft tumours in BALB/c nude mice derived from hsa_circ_0000825-overexpressed TU177 cells showed greater volume and weight than those derived from control TU177 cells. Mechanistically, nuclear-cytoplasmic fractionation assay confirmed that hsa_circ_0000825 was mainly located in the cytoplasm of TU177 and AMC-HN-8 cells. The AGO2-RNA immunoprecipitation (RIP) assay revealed that hsa_circ_0000825 was significantly enriched in the AGO2-precipitated complex in both TU177 and AMC-HN-8 cells, suggesting that this circRNA may function via a competitive endogenous RNA (ceRNA) mechanism. Next, bioinformatics analysis, biotinylated-oligo pull-down assay and dual-luciferase reporter assay verified that miR-766 could be sponged by hsa_circ_0000825 and also target 3'UTR of HOXD10 mRNA. Moreover, miR-766 was shown to be involved in the pro-oncogenic effect of hsa_circ_0000825. This occurred via the mediation of hsa_circ_0000825-enhanced HOXD10 mRNA by the ceRNA mechanism in TU177 and AMC-HN-8 cells. Besides, RNA-binding protein (RBP) ELAVL1 interacted with hsa_circ_0000825 in TU177 and AMC-HN-8 cells, as revealed through bioinformatics analysis, biotinylated-oligo pull-down assays, and RIP assays. ELAVL1 knockdown decreased cell proliferation by 38 % and 34 % in hsa_circ_0000825-overexpressed TU177 and AMC-HN-8 cells (P < 0.05). Similarly, ELAVL1 was involved in the pro-migration and pro-invasion effects of hsa_circ_0000825 overexpression. In addition, comprehensive analysis of mRNA-seq in hsa_circ_0000825-overexpressed TU177 cells, as well as catRAPID and TCGA databases, suggested that ITGB2, HOXD10, and MTCL1 might be crucial downstream target mRNAs of ELAVL1 in LSCC, participating in the hsa_circ_0000825-ELAVL1 axis pro-oncogenic effect. Taken together, hsa_circ_0000825 plays a pro-oncogenic role in LSCC via the miR-766/HOXD10 axis and ELAVL1 and may serve as a promising specific biomarker and therapeutic target for LSCC.

Proteomic characterization of the medial prefrontal cortex in chronic restraint stress mice.

Depression is a prominent contributor to global disability. A growing body of data suggests that depression is associated with the pathophysiology of the medial prefrontal cortex (mPFC), but the underlying mechanisms remain poorly understood. Mice were subjected to chronic restraint stress (CRS) for 3 weeks to create depression models during this investigation. Protein tandem mass tag (TMT) quantification and LC-MS/MS analysis were conducted to examine proteome patterns. Afterwards, to further explore the enrichment of differential proteins and the signaling pathways involved, we annotated these differentially expressed proteins. We confirmed that CRS mice developed depression-like and anxiety-like behaviors. Among the 8081 measured proteins, a total of 15 proteins were found to be differentially expressed. These proteins exhibited functional enrichment in a variety of biological functions, and among these pathways, alterations in synaptic function and autophagy are noteworthy. In addition, we identified a differentially expressed protein called Wnt2b and found that CRS may disrupt synaptic plasticity by affecting the activation of the Wnt2b/ß-catenin pathway. Our findings showed depression-like behaviors in the CRS mouse model and molecular alterations in the mPFC, which may help explain the pathogenesis of depression and identify novel antidepressant medication targets. SIGNIFICANCE: Depression is a prevalent and frequent chronic mental illness and is now a significant contributor to global disability. In this study, we used chronic restraint stress to establish a mouse model of depression, and differentially expressed proteins in the medial prefrontal cortex of depressed model mice were detected by TMT proteomics. Our study verified the presence of altered synaptic function and excessive autophagy in the mPFC of CRS-induced mice from a proteomic perspective. Furthermore, we demonstrated that CRS may disrupt synaptic plasticity by affecting the activation of the Wnt2b/ß-catenin pathway, which may be a key link in the pathogenesis of depression and may provide new insights for identifying new antidepressant drug targets.

Purifying Photon Indistinguishability through Quantum Interference.

Indistinguishability between photons is a key requirement for scalable photonic quantum technologies. We experimentally demonstrate that partly distinguishable single photons can be purified to reach near-unity indistinguishability by the process of quantum interference with ancillary photons followed by heralded detection of a subset of them. We report on the indistinguishability of the purified photons by interfering two purified photons and show improvements in the photon indistinguishability of 2.774(3)% in the low-noise regime, and as high as 10.2(5)% in the high-noise regime.

Effect of group online-based peer support intervention on psychological distress of adolescent and young adult cancer patients: a randomized controlled trial.

PURPOSE: Adolescent and young adult (AYA) cancer patients, aged between 15 to 39 years old, suffer from long-term psychological distress, confronting low self-efficacy and various psychological problems. This study constructs a group online-based peer support intervention combined with offline activities to explore its impact on the psychological distress of AYA cancer patients. METHODS: A randomized, two-arm clinical trial was conducted in which 90 AYA cancer patients were recruited. The control group (N = 45) received conventional psychological care and treatment, and the experimental group (N = 45) received 8 weeks of an online peer support intervention. Outcome measures included psychological distress (Distress Thermometer, DT), anxiety and depression (Hospital Anxiety and Depression Scale, HADS), perceived peer support (Cancer Peer Support Scales, CaPSS), and readiness for return to work (Readiness to Return-To-Work Scale, RRTW). RESULTS: Eight-week peer support intervention was effective in improving psychological distress, anxiety, and depressive symptoms in the experimental group with statistically significant differences (P < 0.05). Time affected psychological distress, anxiety, and depressive symptoms in AYA cancer patients (P < 0.05), and there was an interaction with intervention factors (P < 0.05). The intervention has a positive effect on relieving the psychological status of AYA cancer patients. For readiness for return to work, the experimental group was in the preparation for the action-behavioral stage immediately, 1 month and 3 months after the end of the intervention (P < 0.01), supporting AYA cancer patients who have not returned to work to maintain optimal return-to-work readiness. CONCLUSIONS: The group online-based peer support intervention is popular and has good scientificity, effectiveness, and practical significance for AYA cancer patients. TRIAL REGISTRATION: This study was registered at clinicaltrials.gov. (ChiCTR2100053091, registered on 10 November 2021).

Comparison of clinical research trends and hotspots in allergic rhinitis and asthma from 2013 to 2023 based on bibliometric analysis.

Purpose: To analyze and compare clinical research trends and hot topics in allergic rhinitis (AR) and asthma and provide valuable theoretical data and references for future research. Methods: Clinical studies focusing on AR or asthma published from 2013 to 2023 were retrieved from the Web of Science Core Collection. Eligible articles were screened and analyzed using bibliometrics from multiple indicators. Results: A total of 261 eligible articles on AR and 991 qualified articles on asthma were screened. The following bibliometric analyses identified the Journal of Allergy and Clinical Immunology as the most influential publication on AR and asthma and proved the significant contributions of Harvard University in clinical studies on AR and asthma. The analyses also revealed that the top ten prolific authors for AR were from China, the United Kingdom, Japan, and Germany, whereas the top ten productive authors for asthma were mainly from the USA. Collaborations among countries for AR were relatively concentrated in the Occident, whereas international cooperation on asthma was mainly achieved by the Occident and certain Eastern countries. Conclusions: This study compared and analyzed the current status and evolution of AR and asthma-related clinical research using bibliometric analysis. Additionally, the study comprehensively summarized the impactful authors, institutions, and countries, and revealed the replacement and evolution of hotspots.

Formation of Linear Plasmonic Heterotrimers Using Nanoparticle Docking to DNA Origami Cages.

The fabrication of complex assemblies with interesting collective properties from plasmonic nanoparticles (NPs) is often challenging. While DNA-directed self-assembly has emerged as one of the most promising approaches to forming such complex assemblies, the resulting structures tend to have large variability in gap sizes and shapes, as the DNA strands used to organize these particles are flexible, and the polydispersity of the NPs leads to variability in these critical structural features. Here, we use a new strategy termed docking to DNA origami cages (D-DOC) to organize spherical NPs into a linear heterotrimer with a precisely defined geometrical arrangement. Instead of binding NPs to the exterior of the DNA templates, D-DOC binds the NPs to either the interior or the opening of a 3D cage, which significantly reduces the variability of critical structural features by incorporating multiple diametrically arranged capture strands to tether NPs. Additionally, such a spatial arrangement of the capture strand can work synergistically with shape complementarity to achieve tighter confinement. To assemble NPs via D-DOC, we developed a multistep assembly process that first encapsulates an NP inside a cage and then binds two other NPs to the openings. Microscopic characterization shows low variability in the bond angles and gap sizes. Both UV-vis absorption and surface-enhanced Raman scattering (SERS) measurements showed strong plasmonic coupling that aligned with predictions by electrodynamic simulations, further confirming the precision of the assembly. These results suggest D-DOC could open new opportunities in biomolecular sensing, SERS and fluorescence spectroscopies, and energy harvesting through the self-assembly of NPs into more complex 3D assemblies.

ROS-responsive hydrogels: from design and additive manufacturing to biomedical applications.

Hydrogels with intricate 3D networks and high hydrophilicity have qualities resembling those of biological tissues, making them ideal candidates for use as smart biomedical materials. Reactive oxygen species (ROS) responsive hydrogels are an innovative class of smart hydrogels, and are cross-linked by ROS-responsive modules through covalent interactions, coordination interactions, or supramolecular interactions. Due to the introduction of ROS response modules, this class of hydrogels exhibits a sensitive response to the oxidative stress microenvironment existing in organisms. Simultaneously, due to the modularity of the ROS-responsive structure, ROS-responsive hydrogels can be manufactured on a large scale through additive manufacturing. This review will delve into the design, fabrication, and applications of ROS-responsive hydrogels. The main goal is to clarify the chemical principles that govern the response mechanism of these hydrogels, further providing new perspectives and methods for designing responsive hydrogel materials.

A robust and biodegradable hydroxyapatite/poly(lactide-co-ε-caprolactone) electrospun membrane for dura repair.

Typically occurring after trauma or neurosurgery treatments, dura mater defect and the ensuing cerebrospinal fluid (CSF) leakage could lead to a number of serious complications and even patient's death. Although numerous natural and synthetic dura mater substitutes have been reported, none of them have been able to fulfill the essential properties, such as anti-adhesion, leakage blockage, and pro-dura rebuilding. In this study, we devised and prepared a series of robust and biodegradable hydroxyapatite/poly(lactide-co-ε-caprolactone) (nHA/PLCL) membranes for dura repair via an electrospinning technique. In particular, PLLA/PCL (80/20) was selected for electrospinning due to its mechanical properties that most closely resembled natural dural tissue. Studies by SEM, XRD, water contact angle and in vitro degradation showed that the introduction of nHA would destroy PLCL's crystalline structure, which would further affect the mechanical properties of the nHA/PLCL membranes. When the amount of nHA added increased, so did the wettability and in vitro degradation rate, which accelerated the release of nHA. In addition, the high biocompatibility of nHA/PLCL membranes was demonstrated by in vitro cytotoxicity data. The in vivo rabbit dura repair model results showed that nHA/PLCL membranes provided a strong physical barrier to stop tissue adhesion at dura defects. Meanwhile, the nHA/PLCL and commercial group's CSF had a significantly lower number of inflammatory cells than the control groups, validating the nHA/PLCL's ability to effectively lower the risk of intracranial infection. Findings from H&E and Masson-trichrome staining verified that the nHA/PLCL electrospun membrane was more favorable for fostering dural defect repair and skull regeneration. Moreover, the relative molecular weight of PLCL declined dramatically after 3 months of implantation, according to the results of the in vivo degradation test, but it retained the fiber network structure and promoted tissue growth, demonstrating the good stability of the nHA/PLCL membranes. Collectively, the nHA/PLCL electrospun membrane presents itself as a viable option for dura repair.

Integration RNA bulk and single cell RNA sequencing to explore the change of glycolysis-related immune microenvironment and construct prognostic signature in head and neck squamous cell carcinoma.

BACKGROUND: Glycolysis is an indispensable process for tumor cell,but the effect of glycolysis on the prognosis and immune cell infiltration of head and neck squamous cell carcinoma is not clear. METHODS: Based on RNA bulk and single cell RNA sequencing data of head and neck squamous cell carcinoma from The Cancer Genome Atlas(TCGA) and GSE195832, the effect of glycolysis level on immune cell infiltration was analyzed. Then, we obtained the prognostic genes related to glycolysis through survival analysis to construct prognostic risk signature. Our sample and GSE65858 datasets are used as external verification datasets to verify the validity of the signature. Finally, we used Western blot and cell function assays to determine the relationship between risk genes and glycolysis and the function of prognostic genes. RESULT: The level of glycolysis was related to the prognosis of head and neck tumors (P = 0.0044). The results of immune infiltration analysis of TCGA database showed that high level glycolysis subgroup had less infiltration of macrophages, T cells and monocytes. Results of single cell sequencing analysis validates the above results. Additionally, Five risk genes(MUCL1,TRIML2,RAB3B,SPINK6,IGSF11) were selected to construct signature.Risk score was an independent prognostic factor(P < 0.01). The external validation set also shows the same result. In vitro functional and Western blot assays confirmed that the above five genes affect tumor function and related to the process of glycolysis. CONCLUSION: Glycolysis-related risk signatures can be used to predict the prognosis and immune infiltration of head and neck squamous cell carcinoma.

ZBP1-mediated apoptosis and inflammation exacerbate steatotic liver ischemia/reperfusion injury.

Steatotic donor livers are becoming more and more common in liver transplantation. However, the current use of steatotic grafts is less acceptable than normal grafts due to their higher susceptibility to ischemia/reperfusion (I/R) injury. To investigate the mechanism underlying the susceptibility of steatotic liver to I/R injury, we detected cell death markers and inflammation in clinical donor livers and animal models. We found that caspase-8-mediated hepatic apoptosis is activated in steatotic liver I/R injury. However, ablation of caspase-8 only slightly mitigated steatotic liver I/R injury without affecting inflammation. We further demonstrated that RIPK1 kinase induces both caspase-8-mediated apoptosis and cell death-independent inflammation. Inhibition of RIPK1 kinase significantly protects against steatotic liver I/R injury by alleviating both hepatic apoptosis and inflammation. Additionally, we found that RIPK1 activation is induced by Z-DNA binding protein 1 (ZBP1) but not the canonical TNF-α pathway during steatotic liver I/R injury. Deletion of ZBP1 substantially decreases the steatotic liver I/R injury. Mechanistically, ZBP1 is amplified by palmitic acid-activated JNK pathway in steatotic livers. Upon I/R injury, excessive reactive oxygen species trigger ZBP1 activation by inducing its aggregation independent of the Z-nucleic acids sensing action in steatotic livers, leading to the kinase activation of RIPK1 and the subsequent aggravation of liver injury. Thus, ZBP1-mediated RIPK1-driven apoptosis and inflammation exacerbate steatotic liver I/R injury, which could be targeted to protect steatotic donor livers during transplantation.

Adsorption of humic acid from different organic solid waste compost to phenanthrene, is fluorescence excitation or quenching?

Humic acid (HA) from different organic solid waste (OSW) compost has been shown good adsorption properties for phenanthrene. However, the raw material of HA can affect its structure, resulting in differences in adsorption capacity. Therefore, this study focused on the adsorption characteristics of phenanthrene by HA from different OSW compost. In this work, chicken manure (CM), rice straw (RS) and lawn waste (LW) were selected as sources of composted HA. The adsorption mechanism of HA from different OSW compost were revealed through analytical techniques including three-dimensional fluorescence spectroscopy (EEM), two-dimensional correlation spectroscopy (2DCOS), and Fourier-transform infrared spectroscopy (FTIR). The results suggested that HA from LW compost had a better adsorption affinity for phenanthrene because of its more complex fluorescent component, where C1 as a simple component determined the adsorption process specifically. Furthermore, after HA from LW compost adsorbed phenanthrene, the increase in aromatic -COOH and -NH was the main reason for fluorescence quenching. These results indicated that HA from LW compost had better adsorption effect for phenanthrene. The results of this study were expected to provide a selection scheme for the control of phenanthrene pollution and environmental remediation.

Protein-enriched and anti-inflammatory dietary patterns, healthy lifestyle index and depressive symptoms: A cross-sectional study of 287,945 adults in China.

OBJECTIVES: Depressive symptoms have a considerable negative impact on mental health. This study aimed to understand the relationship between the protein-enriched and anti-inflammatory dietary index scores, modified healthy lifestyle index scores (Modified HLIS), and depressive symptoms. METHODS: This study used convenience sampling to conduct a single-center cross-sectional survey. From January 1, 2015 to December 31, 2020, a total of 287,945 Chinese adults from a health management center of a general hospital completed an online self-reported health questionnaire, which included demographic characteristics, the Dietary Diversity Scale, the Modified Healthy Lifestyle Index Scores and the Patient Health Questionnaire-9. RESULTS: The higher anti-inflammatory dietary index scores (POR = 0.87; 95 % CI: 0.86-0.87; p < 0.001), moderate modified healthy lifestyle index scores (POR = 0.76; 95 % CI: 0.75-0.78; p < 0.001) and sufficient modified healthy lifestyle index scores (POR = 0.53; 95 % CI: 0.52-0.54; p < 0.001) were negatively associated with depressive symptoms, while the higher protein-enriched dietary index scores (POR = 1.01; 95 % CI: 1.01-1.02; p < 0.001) was positively correlated with depressive symptoms. CONCLUSIONS: This study demonstrated that protein-enriched and anti-inflammatory dietary index scores, and multiple healthy lifestyles are associated depressive symptoms in adults.

IGF2BP2-m6A-circMMP9 axis recruits ETS1 to promote TRIM59 transcription in laryngeal squamous cell carcinoma.

Laryngeal squamous cell carcinoma (LSCC) is a common malignancy of the head and neck. Recently, circular RNA (circRNA) has been studied extensively in multisystem diseases. However, there are few research on biological functions and molecular mechanisms of circRNAs in LSCC. CircRNA array was used to detect the differentially expressed circRNAs. Kaplan-Meier and cox regression analysis were used to identify survival based on circMMP9. The qRT-PCR, RNase R treatment, sanger sequencing and in situ hybridization were used to verify circMMP9 expression, characteristics and localization in LSCC tissues and cells. Functionally, colony formation, MTS, transwell and in vivo assays were proceeded to detect the biological function of circMMP9 in LSCC progression. The RNA-seq was conducted to identify the molecular targets of circMMP9. Mechanically, MeRIP, RNA Immunoprecipitation (RIP), RNA pulldown, Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays were carried on to verify the regulatory mechanism of circMMP9. CircMMP9 was discovered upregulated in LSCC tissues and cells, and high level of circMMP9 was associated with poor prognosis, low degree of pathological grading, high TNM stage and lymph node metastasis of LSCC. CircMMP9 knockdown prevented LSCC progression both in vitro and in vivo, whereas, circMMP9 overexpression had the opposite effect. CircMMP9 was stabilized by IGF2BP2 in m6A-dependent manner. TRIM59 was identified as downstream target of circMMP9. CircMMP9 recruited ETS1 to stimulate TRIM59 transcription. Moreover, TRIM59 accelerated LSCC progression via activating the PI3K/AKT signal pathway. Our findings offered a unique regulatory mechanism for circMMP9 in LSCC, as well as a novel proof that circMMP9 may be utilize as a diagnostic marker and therapeutic target for LSCC patients.

Robust and Multifunctional Therapeutic Nanoparticles against Peritonitis-Induced Sepsis.

Apart from bacterial growth and endotoxin generation, the excessive production of reactive radicals linked with sepsis also has a substantial impact on triggering an inflammatory response and further treatment failure. Hence, the rational design and fabrication of robust and multifunctional nanoparticles (NPs) present a viable means of overcoming this dilemma. In this study, we used antibiotic polymyxin B (PMB) and antioxidant natural polyphenolic protocatechualdehyde (PCA) to construct robust and multifunctional NPs for sepsis treatment, leveraging the rich chemistries of PCA. The PMB release profile from the NPs demonstrated pH-responsive behavior, which allowed the NPs to exhibit effective bacterial killing and radical scavenging properties. Data from in vitro cells stimulated with H2O2 and lipopolysaccharide (LPS) showed the multifunctionalities of NPs, including intracellular reactive oxygen species (ROS) scavenging, elimination of the bacterial toxin LPS, inhibiting macrophage M1 polarization, and anti-inflammation capabilities. Additionally, in vivo studies further demonstrated that NPs could increase the effectiveness of sepsis treatment by lowering the bacterial survival ratio, the expression of the oxidative marker malondialdehyde (MDA), and the expression of inflammatory cytokine TNF-α. Overall, this work provides ideas of using those robust and multifunctional therapeutic NPs toward enhanced sepsis therapy efficiency.

Associations between healthy lifestyle behavioral patterns and mental health problems: A latent class analysis of 161,744 Chinese young adults.

BACKGROUND: Youth mental health problems are a public health priority. Multiple healthy lifestyle behaviors may cluster into healthy lifestyle behavioral patterns (HLBPs) that increase mental health risks in adolescents and older adults, but little is known regarding young adults. This study aimed to explore the associations between cluster HLBPs and mental health problems in young adults. METHODS: We selected 161,744 young adults aged 20-39 as participants from the database of a Chinese general hospital health management center for the years 2015-2020. The latent class analysis was used to identify HLBPs. RESULTS: A total of 15.0 % of young adults have at least one mental health problem. Five clusters of HLBPs were identified, characterized as low-risk class (1.6 %), moderate-risk class 1 (12.0 %), moderate-risk class 2 (2.1 %), moderate-risk class 3 (56.8 %), and high-risk class (27.4 %). The odds ratios (ORs) for young adults with two mental health problems increased with the risk grade of HLBPs, while the ORs for young adults with one or three mental health problems ranged from high to low according to the risk grade of HLBPs: high-risk class, moderate-risk class 2, moderate-risk class 3, moderate-risk class 1. LIMITATIONS: Cross-sectional design and no causal conclusions could be drawn. CONCLUSION: Young adults demonstrated a cluster phenomenon of healthy lifestyle behaviors and significant associations between HLBPs and mental health problems. Young adults with a higher risk grade for HLBPs were more likely to have mental health problems. Different HLBPs should be taken into account when implementing mental health interventions.

Attenuating Epithelial-to-Mesenchymal Transition in Cancer through Angiopoietin-Like 4 Inhibition in a 3D Tumor Microenvironment Model.

Epithelial-to-mesenchymal transition (EMT) plays a crucial role in metastatic cancer progression, and current research, which relies heavily on 2D monolayer cultures, falls short in recapitulating the complexity of a 3D tumor microenvironment. To address this limitation, a transcriptomic meta-analysis is conducted on diverse cancer types undergoing EMT in 2D and 3D cultures. It is found that mechanotransduction is elevated in 3D cultures and is further intensified during EMT, but not during 2D EMT. This analysis reveals a distinct 3D EMT gene signature, characterized by extracellular matrix remodeling coordinated by angiopoietin-like 4 (Angptl4) along with other canonical EMT regulators. Utilizing hydrogel-based 3D matrices with adjustable mechanical forces, 3D cancer cultures are established at varying physiological stiffness levels. A YAP:EGR-1 mediated up-regulation of Angptl4 expression is observed, accompanied by an upregulation of mesenchymal markers, at higher stiffness during cancer EMT. Suppression of Angptl4 using antisense oligonucleotides or anti-cAngptl4 antibodies leads to a dose-dependent abolishment of EMT-mediated chemoresistance and tumor self-organization in 3D, ultimately resulting in diminished metastatic potential and stunted growth of tumor xenografts. This unique programmable 3D cancer cultures simulate stiffness levels in the tumor microenvironment and unveil Angptl4 as a promising therapeutic target to inhibit EMT and impede cancer progression.

Predicting ICU readmission risks in intracerebral hemorrhage patients: Insights from machine learning models using MIMIC databases.

BACKGROUND: Intracerebral hemorrhage (ICH) is a stroke subtype characterized by high mortality and complex post-event complications. Research has extensively covered the acute phase of ICH; however, ICU readmission determinants remain less explored. Utilizing the MIMIC-III and MIMIC-IV databases, this investigation develops machine learning (ML) models to anticipate ICU readmissions in ICH patients. METHODS: Retrospective data from 2242 ICH patients were evaluated using ICD-9 codes. Recursive feature elimination with cross-validation (RFECV) discerned significant predictors of ICU readmissions. Four ML models-AdaBoost, RandomForest, LightGBM, and XGBoost-underwent development and rigorous validation. SHapley Additive exPlanations (SHAP) elucidated the effect of distinct features on model outcomes. RESULTS: ICU readmission rates were 9.6% for MIMIC-III and 10.6% for MIMIC-IV. The LightGBM model, with an AUC of 0.736 (95% CI: 0.668-0.801), surpassed other models in validation datasets. SHAP analysis revealed hydrocephalus, sex, neutrophils, Glasgow Coma Scale (GCS), specific oxygen saturation (SpO2) levels, and creatinine as significant predictors of readmission. CONCLUSION: The LightGBM model demonstrates considerable potential in predicting ICU readmissions for ICH patients, highlighting the importance of certain clinical predictors. This research contributes to optimizing patient care and ICU resource management. Further prospective studies are warranted to corroborate and enhance these predictive insights for clinical utilization.

Diverse Post-Metathesis Reactivities of Mixed Amido-Isothiocyanato Molybdenum Complexes.

Attempts to prepare mixed isothiocyanato-bis(imido) MoVI complexes led to the discovery of post-metathesis rearrangements toward three distinct products (1-3), which feature the NCS-derived chelators [N(NMe2)CS]2- (L1 in dinuclear 1 and 2) and [N(SiMe3)(NMe2)CS]- (L2 in mononuclear 3). Notably, the preparation of bidentate ligand L1 and its coordination chemistry are unprecedented. Together with computational studies, it is proposed that the putative "mono-substituted" intermediate [Mo(NtBu)2(NMe2)(NCS)] serves as the common starting point for the observed molecular transformations. Construction of the [Mo(NtBu)2(NCS)2] core was ultimately possible in the presence of additional stabilizing donors (THF or PMe3), which yielded the complexes [Mo(NtBu)2(NCS)2(THF)2] (4) and [Mo(NtBu)2(NCS)2(PMe3)2] (5).