Potential Molecular Markers for Cholecystic Inflammation-Induced Carcinogenesis Based on RNA-Seq Gene Screening.

BACKGROUND: Uncontrolled inflammation plays an important role in the initiation and progression of tumors. The repeated circulation and continuous stimulation of gallbladder epithelium caused by gallstones is an important risk factor for gallbladder cancer. METHODS: To study pathogenesis, samples were collected for chronic cholecystitis caused by gallstones and early and advanced gallbladder cancer with gallstones and subjected to RNA-seq analysis. Gene Ontology and Kyoto Gene and Genome Encyclopedia analyses were used to elucidate the protein-protein interaction network and identify differentially expressed genes. RESULTS: Nine potential molecular markers, VTN, CHAD, AKR1C4, ABCC2, AOX1, ADH1A, ADH1C, PLA2G2A, and CYP4F3, with elevated expression gradients in cholecystitis and early and advanced gallbladder cancer, were identified. Using qPCR and immunohistochemistry on clinical tissues, we confirmed three factors, VTN, CYP4F3, and AOX1, to be worthy of further research. To demonstrate that these three genes are potential molecular markers for gallbladder cancer, their cellular biological functions were confirmed in gallbladder cancer cell lines through siRNA transfection. CONCLUSION: The potential molecular markers CYP4F3, VTN, and AOX1 for cholecystitis and different stages of gallbladder cancer were identified. Further studies on differentially expressed genes vital in gallbladder cancer progression can help provide potential targets for the early diagnosis and treatment of gallbladder cancer.

The role of serum lipid in predicting coronary artery lesions and intravenous immunoglobulin resistance in Kawasaki disease: a cohort study.

OBJECTIVE: To assess the predictive value of the serum lipid profile for initial intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs) in patients with Kawasaki disease (KD). METHODS: This retrospective cohort study enrolled patients with KD and divided them into IVIG-responsive and IVIG-resistant groups. They were also stratified based on the presence of CALs (CALs and non-CALs groups). Clinical, echocardiographic and biochemical values were evaluated. A subgroup analysis was performed on complete and incomplete KD. Predictors of initial IVIG resistance and CALs were determined by multivariate logistic regression analysis. RESULTS: A total of 649 KD patients were enrolled: 151 had CALs and 76 had initial IVIG resistance. Low-density lipoprotein cholesterol (LDL-C) was significantly lower in the IVIG-resistant group than in the IVIG-responsive group. LDL-C and apolipoprotein (Apo) B were significantly lower in the CALs group compared with the non-CALs group. Multivariate logistic regression failed to identify the serum lipid profile (LDL-C, Apo A or Apo B) as an independent risk factor for initial IVIG resistance or CALs in KD patients. CONCLUSION: KD patients might have dyslipidaemia in the acute phase, but the serum lipid profile might not be suitable as a single predictor for initial IVIG resistance or CALs.

The cGAS-STING pathway in cardiovascular diseases: from basic research to clinical perspectives.

The cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase-stimulator of interferon genes (cGAS-STING) signaling pathway, an important component of the innate immune system, is involved in the development of several diseases. Ectopic DNA-induced inflammatory responses are involved in several pathological processes. Repeated damage to tissues and metabolic organelles releases a large number of damage-associated molecular patterns (mitochondrial DNA, nuclear DNA, and exogenous DNA). The DNA fragments released into the cytoplasm are sensed by the sensor cGAS to initiate immune responses through the bridging protein STING. Many recent studies have revealed a regulatory role of the cGAS-STING signaling pathway in cardiovascular diseases (CVDs) such as myocardial infarction, heart failure, atherosclerosis, and aortic dissection/aneurysm. Furthermore, increasing evidence suggests that inhibiting the cGAS-STING signaling pathway can significantly inhibit myocardial hypertrophy and inflammatory cell infiltration. Therefore, this review is intended to identify risk factors for activating the cGAS-STING pathway to reduce risks and to simultaneously further elucidate the biological function of this pathway in the cardiovascular field, as well as its potential as a therapeutic target.

Synthesis of Nitrones and Nitroalkanes via Chiral Cyclic Imines.

A series of structurally chiral cyclic imines efficiently yields chiral nitrones and nitroalkanes. This is the first report of the synthesis of nitro groups by C═N bond cleavage of imines through a nitrone intermediate.

A SAW-Based Programmable Controlled RNA Detecting Device: Rapid In Situ Cytolysis-RNA Capture-RNA Release-PCR in One Mini Chamber.

Viral RNA detection is crucial in preventing and treating early infectious diseases. Traditional methods of RNA detection require a large amount of equipment and technical personnel. In this study, proposed a programmable controlled surface acoustic wave (SAW)-based RNA detecting device has been proposed. The proposed device can perform the entire viral RNA detection process, including cell lysis by cell-microparticle collision through SAW-induced liquid whirling, RNA capture by SAW-suspended magnetic beads, RNA elution through SAW-induced high streaming force, and PCR thermal cycling through SAW-generated heat. The device has completed all RNA detection steps in one mini chamber, requiring only 489 µl reagents for RNA extraction, much smaller than the amount used in manual RNA extraction (2065 µl). The experimental results have shown that PCR results from the device are comparable to those achieved via commercial qPCR instrumental detection. This work has demonstrated the potential of SAW-based lab-on-a-chip devices for point-of-care testing and provided a novel approach for rapidly detecting infectious diseases.

Polyprodrug nanomedicine for chemiexcitation-triggered self-augmented cancer chemotherapy and gas therapy.

Carbon monoxide (CO) has emerged as a potential antitumor agent by inducing the dysfunction of mitochondria and the apoptosis of cancer cells. However, it remains challenging to deliver appropriate amount of CO into tumor to ensure efficient tumor growth suppression with minimum side effects. Herein we developed a CO prodrug-loaded nanomedicine based on the self-assembly of camptothecin (CPT) polyprodrug amphiphiles. The polyprodrug nanoparticles readily dissociate upon exposure to endogenous H2O2 in the tumor, resulting in rapid release of CPT and generation of high-energy intermediate dioxetanedione. The latter can transfer the energy to neighboring CO prodrugs to activate CO production by chemiexcitation, while CPT promotes the generation of H2O2 in tumors, which in turn facilitates cascade CPT and CO release. As a result, the polyprodrug nanoparticles display remarkable tumor suppression in both subcutaneous and orthotopic breast tumor-bearing mice owing to the self-augmented CPT release and CO generation. In addition, no obvious systemic toxicity was observed in mice treated with the metal-free CO prodrug-loaded nanomedicine, suggesting the good biocompatibility of the polyprodrug nanoparticles. Our work provides new insights into the design and construction of polyprodrug nanomedicines for synergistic chemo/gas therapy.

Association Between Vitamin D Level and Clinical Outcomes of Assisted Reproductive Treatment: A Systematic Review and Dose-Response Meta-Analysis.

The investigation about association between vitamin D level and clinical outcomes of assisted reproductive treatment showed various outcomes. This study aimed to review the correlation between vitamin D and outcomes of assisted reproductive treatment. The search was registered on the PROSPERO database (CRD42023458040). PubMed, Embase, Medline, ClinicalTrials.gov, and Cochrane databases were searched up to July 2023. Twenty-three observational studies were selected for meta-analysis. Comparing groups with deficient and 'insufficient + sufficient' vitamin D level, meta-analysis showed positive correlation between clinical pregnancy rate and vitamin D (OR 0.81, 95%CI: 0.70, 0.95, P = 0.0001). Comparing groups with 'deficient + insufficient' and sufficient vitamin D level, meta-analysis showed positive correlation between vitamin D and clinical pregnancy rate (OR 0.71, 95%CI: 0.55, 0.91, P = 0.006), vitamin D and live birth rate (OR 0.69, 95%CI: 0.54, 0.89, P = 0.003). Subgroup analysis did not show the source of high heterogeneity. No correlation was found in biochemical pregnancy rate, ongoing pregnancy rate, miscarriage rate and implantation rate. In dose-response meta-analysis, a nonlinear association was found between vitamin D levels and outcomes when levels are below approximately 24 ng/L. The study shows that vitamin D level is associated with clinical pregnancy rate and live birth rate. Low vitamin D level does not influence biochemical pregnancy rate, ongoing pregnancy rate, miscarriage rate and implantation rate. Furthermore, 24 ng/L may be a possible threshold of vitamin D concentration in assisted reproduction therapy.

Internal fistula stenosis with true pseudoaneurysm formation in a patient on maintenance hemodialysis: A case report.

BACKGROUND: Arteriovenous fistula stenosis can directly lead to the formation of autologous arteriovenous fistula aneurysms (AVFAs), but the coexistence of true and pseudoaneurysms is relatively rare. The coexistence of true and pseudoaneurysms increases the risk of rupture of the arteriovenous fistula and complicates subsequent surgical intervention, potentially posing a threat to the patient's life, and thus requires significant attention. CASE PRESENTATION: The patient presented with arteriovenous fistula (AVF) after hemodialysis 6 years ago. 2 years ago, the patient presented with a mass that had formed near the left forearm arteriovenous fistula and gradually increased in size. Preoperatively, the AVF stenosis was identified as the cause of the mass formation, and the patient was operated on. First, the blood flow was controlled to reduce the pressure at the aneurysm, and then the incision was enlarged to separate the AVF anastomosis from the mass area. The stenotic segment of the true and pseudo aneurysms and cephalic vein was removed and the over-dilated proximal cephalic vein was locally narrowed and subsequently anastomosed with the proximal radial artery to create AVF. The patient was dialyzed with an internal fistula the next day and showed no clinical manifestations related to end-limb ischemia. CONCLUSION: We removed a true pseudoaneurysm in AVF and secured the patient's vascular access. This report provides an effective strategy to manage this condition.

Efficacy and safety of PD-1/PD-L1 immune checkpoint inhibitors in the treatment of recurrent ovarian cancer: A systematic review and meta-analysis.

BACKGROUND: Recurrent ovarian cancer (OC) presents a significant therapeutic challenge with limited treatment success. Programmed cell death protein 1 (PD-1/PD-L1) immune checkpoint inhibitors have emerged as a potential treatment avenue, necessitating a systematic review and meta-analysis to evaluate their efficacy and safety. METHODS: Adhering to preferred reporting items for systematic reviews and meta-analyses guidelines, we conducted a comprehensive literature search across PubMed, Embase, Web of Science, and Cochrane Library, culminating in the inclusion of studies focusing on the treatment of recurrent OC with PD-1/PD-L1 inhibitors. Studies were evaluated using the Newcastle-Ottawa Scale and analyzed using fixed or random effects models depending on heterogeneity levels. RESULTS: Our search yielded 1215 articles, with 6 meeting the inclusion criteria for final analysis. Studies varied in size and reported median age, overall survival (OS), progression-free survival (PFS), and adverse events. The meta-analysis showed improved Objective Response Rates (ORR), Disease Control Rate (DCR), and PFS in patients treated with PD-1/PD-L1 inhibitors. The overall adverse event rate was 17.9%, indicating a need for careful patient selection and monitoring. No significant publication bias was detected, enhancing the reliability of our findings. CONCLUSIONS: PD-1/PD-L1 inhibitors offer a promising treatment option for recurrent OC, improving ORR, DCR, and PFS. However, the higher incidence of adverse events necessitates a cautious approach to their use. Future research should focus on long-term outcomes, biomarker identification, and optimal combination therapies.

Mechanism of fibroblast growth factor 1 regulating fatty liver disorder in mule ducks.

Mule ducks tend to accumulate abundant fat in their livers via feeding, which leads to the formation of a fatty liver that is several times larger than a normal liver. However, the mechanism underlying fatty liver formation has not yet been elucidated. Fibroblast growth factor 1 (FGF1), a member of the FGF superfamily, is involved in cellular lipid metabolism and mitosis. This study aims to investigate the regulatory effect of FGF1 on lipid metabolism disorders induced by complex fatty acids in primary mule duck liver cells and elucidate the underlying molecular mechanism. Hepatocytes were induced by adding 1,500:750 µmol/L oleic and palmitic acid concentrations for 36 h, which were stimulated with FGF1 concentrations of 0, 10, 100, and 1000 ng/mL for 12 h. The results showed that FGF1 significantly reduced the hepatic lipid droplet deposition and triglyceride content induced by complex fatty acids; it also reduced oxidative stress; decreased reactive oxygen species fluorescence intensity and malondialdehyde content; upregulated the expression of antioxidant factors nuclear factor erythroid 2 related factor 2 (Nrf2), HO-1, and NQO-1; significantly enhanced liver cell activity; promoted cell cycle progression; inhibited cell apoptosis; upregulated cyclin-dependent kinase 1 (CDK1) and BCL-2 mRNA expression; and downregulated Bax and Caspase-3 expression. In addition, FGF1 promoted AMPK phosphorylation, activated the AMPK pathway, upregulated AMPK gene expression, and downregulated the expression of SREBP1 and ACC1 genes, thereby alleviating excessive fat accumulation in liver cells induced by complex fatty acids. In summary, FGF1 may alleviate lipid metabolism disorders induced by complex fatty acids in primary mule duck liver cells by activating the AMPK signaling pathway.

The role of interleukin-20 in liver disease: Functions, mechanisms and clinical applications.

Liver disease is a severe public health concern worldwide. There is a close relationship between the liver and cytokines, and liver inflammation from a variety of causes leads to the release and activation of cytokines. The functions of cytokines are complex and variable, and are closely related to their cellular origin, target molecules and mode of action. Interleukin (IL)-20 has been studied as a pro-inflammatory cytokine that is expressed and regulated in some diseases. Furthermore, accumulating evidences has shown that IL-20 is highly expressed in clinical samples from patients with liver disease, promoting the production of pro-inflammatory molecules involved in liver disease progression, and antagonists of IL-20 can effectively inhibit liver injury and produce protective effects. This review highlights the potential of targeting IL-20 in liver diseases, elucidates the potential mechanisms of IL-20 inducing liver injury, and suggests multiple viable strategies to mitigate the pro-inflammatory response to IL-20. Genomic CRISPR/Cas9-based screens may be a feasible way to further explore the signaling pathways and regulation of IL-20 in liver diseases. Nanovector systems targeting IL-20 offer new possibilities for the treatment and prevention of liver diseases.

Fabrication of Loose Nanofiltration Membrane by Crosslinking TEMPO-Oxidized Cellulose Nanofibers for Effective Dye/Salt Separation.

Dye/salt separation has gained increasing attention in recent years, prompting the quest to find cost-effective and environmentally friendly raw materials for synthesizing high performance nanofiltration (NF) membrane for effective dye/salt separation. Herein, a high-performance loose-structured NF membrane was fabricated via a simple vacuum filtration method using a green nanomaterial, 2,2,6,6-tetramethylpiperidine-1-oxide radical (TEMPO)-oxidized cellulose nanofiber (TOCNF), by sequentially filtrating larger-sized and finer-sized TOCNFs on a microporous substrate, followed by crosslinking with trimesoyl chloride. The resulting TCM membrane possessed a separating layer composed entirely of pure TOCNF, eliminating the need for other polymer or nanomaterial additives. TCM membranes exhibit high performance and effective dye/salt selectivity. Scanning Electron Microscope (SEM) analysis shows that the TCM membrane with the Fine-TOCNF layer has a tight layered structure. Further characterizations via Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) confirmed the presence of functional groups and chemical bonds of the crosslinked membrane. Notably, the optimized TCM-5 membrane exhibits a rejection rate of over 99% for various dyes (Congo red and orange yellow) and 14.2% for NaCl, showcasing a potential candidate for efficient dye wastewater treatment.

Preoperative prediction of microvascular invasion classification in hepatocellular carcinoma based on clinical features and MRI parameters.

Microvascular invasion (MVI) in hepatocellular carcinoma (HCC) is a critical pathological factor and the degree of MVI influences treatment decisions and patient prognosis. The present study aimed to predict the MVI classification based on preoperative MRI features and clinical parameters. The present retrospective cohort study included 150 patients (training cohort, n=108; validation cohort, n=42) with pathologically confirmed HCC. Clinical and imaging characteristics data were collected from Shengli Oilfield Central Hospital (Dongying, China). Univariate and multivariate logistic regression analyses were conducted to assess the association of clinical variables and MRI parameters with MVI (grade M1 and M2) and the M2 classification. Nomograms were developed based on the predictive factors of MVI and the M2 classification. The discrimination capability, calibration and clinical usefulness of the nomograms were evaluated. Multivariate analysis revealed an association between the Lens culinaris agglutinin-reactive fraction of α-fetoprotein, protein induced by vitamin K absence-II and tumor margin and MVI-positive status, while peritumoral enhancement and tumor size were demonstrated to be marginal predictors, but were also included in the nomogram. However, among MVI-positive patients, only peritumoral hypointensity and tumor size were demonstrated to be risk factors for the M2 classification. The nomograms, incorporating these variables, exhibited a strong ability to discriminate between MVI-positive and MVI-negative patients with HCC in both the training and validation cohort [area under the curve (AUC), 0.877 and 0.914, respectively] and good performance in predicting the M2 classification in the training and validation cohorts (AUC, 0.720 and 0.782, respectively). Nomograms incorporating clinical parameters and preoperative MRI features demonstrated promising potential as straightforward and effective tools for predicting MVI and the M2 classification in patients with HCC. Such predictive tools could aid in the judicious selection of optimal clinical treatments.

Physiology and transcriptomic analysis revealed the mechanism of silicon promoting cadmium accumulation in Sedum alfredii Hance.

Silicon (Si) effectively promote the yield of many crops, mainly due to its ability to enhance plants resistance to stress. However, how Si helps hyperaccumulators to extract Cadmium (Cd) from soil has remained unclear. In this study, Sedum alfredii Hance (S. alfredii) was used as material to study how exogenous Si affected biomass, Cd accumulation, antioxidation, cell ultrastructure, subcellular distribution and changes in gene expression after Cd exposure. The study has shown that as Si concentration increases (1, 2 mM), the shoot biomass of plants increased by 33.1%-63.6%, the Cd accumulation increased by 31.9%-96.6%, and the chlorophyll, carotenoid content, photosynthetic gas exchange parameters significantly increased. Si reduced Pro and MDA, promoted the concentrations of SOD, CAT and POD to reduce antioxidant stress damage. In addition, Si promoted GSH and PC to chelate Cd in vacuoles, repaired damaged cell ultrastructure, improved the fixation of Cd and cell wall (especially in pectin), and reduced the toxic effects of Cd. Transcriptome analysis found that genes encoding Cd detoxification, Cd absorption and transport were up-regulated by Si supplying, including photosynthetic pathways (PSB, LHCB, PSA), antioxidant defense systems (CAT, APX, CSD, RBOH), cell wall biosynthesis such as pectinesterase (PME), chelation (GST, MT, NAS, GR), Cd absorption (Nramp3, Nramp5, ZNT) and Cd transport (HMA, PCR). Our result revealed the tentative mechanism of Si promotes Cd accumulation and enhances Cd tolerance in S. alfredii, and thereby provides a solid theoretical support for the practical use of Si fertilizer in phytoextraction.

Integrative Single-Cell Analysis of Cardiomyopathy Identifies Differences in Cell Stemness and Transcriptional Regulatory Networks among Fibroblast Subpopulations.

Background: Cardiomyopathy encompasses a broad spectrum of diseases affecting myocardial tissue, characterized clinically by abnormalities in cardiac structure, heart failure, and/or arrhythmias. Clinically heterogeneous, major types include dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RM), ischemic cardiomyopathy (ICM), among which DCM is more prevalent, while ICM exhibits higher incidence and mortality rates. Myocardial injury during cardiomyopathy progression may lead to myocardial fibrosis. Failure to intervene early and inhibit the process of myocardial fibrosis may culminate in heart failure. Cardiac fibroblasts constitute crucial cellular components determining the extent and quality of myocardial fibrosis, with various subpopulations exerting diverse roles in cardiomyopathy progression. Despite this, understanding of the cellular plasticity and transcriptional regulatory networks of cardiac fibroblasts in cardiomyopathy remains limited. Therefore, in this study, we conducted comprehensive single-cell analysis of cardiac fibroblasts in cardiomyopathy to explore differences in cellular plasticity and transcriptional regulatory networks among fibroblast subpopulations, with the aim of providing as many useful references as possible for the diagnosis, prognosis, and treatment of cardiomyopathy. Materials and Methods: Cells with mitochondrial gene expression comprising >20% of total expressed genes were excluded. Differential expression genes (DEGs) and stemness genes within cardiac fibroblast subpopulations were subjected to Gene Ontology (GO) analysis of biological processes (BP) and AUCell analysis. Monocle software was employed to analyze the pseudo-temporal trajectory of cardiac fibroblasts in cardiomyopathy. Additionally, the Python package SCENIC was utilized to assess enrichment of transcription factors and activity of regulators within cardiac fibroblast subpopulations in cardiomyopathy. Results: Following batch effect correction, 179,927 cells were clustered into 32 clusters, designated as T_NK cells, endothelial cells, myeloid cells, fibroblasts, pericytes, SMCs, CMs, proliferating cells, EndoCs, and EPCs. Among them, 8148 fibroblasts were further subdivided into 4 subpopulations, namely C0 THBS4+ Fibroblasts, C1 LINC01133+ Fibroblasts, C2 FGF7+ Fibroblasts, and C3 AGT + Fibroblasts. Results from GO_BP and AUCell analyses suggest that C3 AGT + Fibroblasts may be associated with immune response activation, protein transport, and myocardial contractile function, correlating with disease progression in cardiomyopathy. Transcription factor enrichment analysis indicates that FOS is the most significant TF in C3 AGT + Fibroblasts, also associated with the M1 module, possibly implicated in protein hydrolysis, intracellular DNA replication, and cell proliferation. Moreover, correlation analysis of transcriptional regulatory activity between fibroblast subpopulations reveals a more pronounced heterogeneity within C3 AGT + Fibroblasts in cardiomyopathy. Conclusion: C3 AGT + Fibroblasts exhibit increased sensitivity towards adverse outcomes in cardiomyopathy, such as myocardial fibrosis and impaired cardiac contractile function, compared to other cardiac fibroblast subpopulations. The differential cellular plasticity and transcriptional regulatory activity between C3 AGT + Fibroblasts and other subgroups offer new perspectives for targeting fibroblast subpopulation activity to treat cardiomyopathy. Additionally, stemness genes EPAS1 and MYC, along with the regulator FOS, may play roles in modulating the biological processes of cardiac fibroblasts in cardiomyopathy.

Long-term relapse-free survival enabled by integrating targeted antibacteria in antitumor treatment.

The role of tumor-resident intracellular microbiota (TRIM) in carcinogenesis has sparked enormous interest. Nevertheless, the impact of TRIM-targeted antibacteria on tumor inhibition and immune regulation in the tumor microenvironment (TME) remains unexplored. Herein, we report long-term relapse-free survival by coordinating antibacteria with antitumor treatment, addressing the aggravated immunosuppression and tumor overgrowth induced by TRIM using breast and prostate cancer models. Combining Ag+ release with a Fenton-like reaction and photothermal conversion, simultaneous bacteria killing and multimodal antitumor therapy are enabled by a single agent. Free of immune-stimulating drugs, the agent restores antitumor immune surveillance and activates immunological responses. Secondary inoculation and distal tumor analysis confirm lasting immunological memory and systemic immune responses. A relapse-free survival of >700 days is achieved. This work unravels the crucial role of TRIM-targeted antibacteria in tumor inhibition and unlocks an unconventional route for immune regulation in TME and a complete cure for cancer.

Enhanced burn wound healing by controlled-release 3D ADMSC-derived exosome-loaded hyaluronan hydrogel.

Adipose mesenchymal stem cell (ADMSC)-derived exosomes (ADMSC-Exos) have shown great potential in regenerative medicine and been evidenced benefiting wound repair such as burns. However, the low yield, easy loss after direct coating, and no suitable loading system to improve their availability and efficacy hinder their clinical application for wound healing. And few studies focused on the comparison of biological functions between exosomes derived from different culture techniques, especially in exosome-releasing hydrogel system. Therefore, we designed a high-performance exosome controllable releasing hydrogel system for burn wound healing, namely loading 3D-printed microfiber culture-derived exosomes in a highly biocompatible hyaluronic acid (HA). In this project, we compared the biological functions in vitro and in a burn model among exosomes derived from the conventional two-dimensional (2D) plate culture (2D-Exos), microcarrier culture (2.5D-Exos), and 3D-printed microfiber culture (3D-Exos). Results showed that compared with 2D-Exos and 2.5D-Exos, 3D-Exos promoted HACATs and HUVECs cell proliferation and migration more significantly. Additionally, 3D-Exos had stronger angiogenesis-promoting effects in tube formation of (HUVECs) cells. Moreover, we found HA-loaded 3D-Exos showed better burn wound healing promotion compared to 2D-Exos and 2.5D-Exos, including accelerated burn wound healing rate and better collagen remodeling. The study findings reveal that the HA-loaded, controllable-release 3D-Exos repair system distinctly augments therapeutic efficacy in terms of wound healing, while concurrently introducing a facile application approach. This system markedly bolsters the exosomal loading efficiency, provides a robust protective milieu, and potentiates the inherent biological functionalities of the exosomes. Our findings provide a rationale for more efficient utilization of high-quality and high-yield 3D exosomes in the future, and a novel strategy for healing severe burns.

Biobased Inks Based on Cuttlefish Ink and Cellulose Nanofibers for Biodegradable Patterned Soft Actuators.

Soft actuators with stimuli-responsive and reversible deformations have shown great promise in soft robotics. However, some challenges remain in existing actuators, such as the materials involved derived from nonrenewable resources, complex and nonscalable preparation methods, and incapability of complex and programmable deformation. Here, a biobased ink based on cuttlefish ink nanoparticles (CINPs) and cellulose nanofibers (CNFs) was developed, allowing for the preparation of biodegradable patterned actuators by direct ink writing technology. The hybrid CNF/CINP ink displays good rheological properties, allowing it to be accurately printed on a variety of flexible substrates. A bilayer actuator was developed by printing an ink layer on a biodegradable poly(lactic acid) film using extrusion-based 3D printing technology, which exhibits reversible and large bending behavior under the stimuli of humidity and light. Furthermore, programmable and reversible folding and coiling deformations in response to stimuli have been achieved by adjusting the ink patterns. This work offers a fast, scalable, and cost-effective strategy for the development of biodegradable patterned actuators with programmable shape-morphing.

Exposure to per- and polyfluoroalkyl substances in lung cancer patients and their associations with clinical health indicators.

Per- and polyfluoroalkyl substances (PFASs) have potential carcinogenicity, immunotoxicity, and hepatotoxicity. Research has been conducted on PFAS exposure in people to discuss their potential health effects, excluding lung cancer. In this study, we recruited participants (n = 282) with lung cancer from Heilongjiang Province, northeast China. The PFAS concentrations were measured in their serum to fill the data gap of exposure, and relationships were explored in levels between PFASs and clinical indicators of tumor, immune and liver function. Ten PFASs were found in over 80 % of samples and their total concentrations were 5.27-152 ng/mL, with the highest level for perfluorooctanesulfonate (median: 12.4 ng/mL). Long-chain PFASs were the main congeners and their median concentration (20.5 ng/mL) was nearly three times to that of short-chain PFASs (7.61 ng/mL). Significantly higher concentrations of perfluorobutanoic acid, perfluorononanoic acid and perfluorohexanesulfonate were found in males than in females (p < 0.05). Serum levels of neuro-specific enolase were positively associated with perfluoropentanoic acid in all participants and were negatively associated with perfluorononanesulfonate in females (p < 0.05, multiple linear regression models). Exposure to PFAS mixture was significantly positively associated with the lymphocytic absolute value (difference: 0.224, 95% CI: 0.018, 0.470; p < 0.05, quantile g-computation models) and serum total bilirubin (difference: 2.177, 95% CI: 0.0335, 4.33; p < 0.05). Moreover, PFAS exposure can affect γ-glutamyl transpeptidase through several immune markers (p < 0.05, mediating test). Our results suggest that exposure to certain PFASs could interfere with clinical indicators in lung cancer patients. To our knowledge, this is the first study to detect serum PFAS occurrence and check their associations with clinical indicators in lung cancer patients.

Spontaneous miscarriage and social support in predicting risks of depression and anxiety: a cohort study in UK Biobank.

BACKGROUND: It is still unclear whether social support can moderate the high risk of depression and anxiety due to spontaneous miscarriage. OBJECTIVE: This study prospectively investigated the associations of spontaneous miscarriage with risks of depression and anxiety, and evaluated the interactions between spontaneous miscarriage and the degree of social support in relation to depression and anxiety risks. STUDY DESIGN: A total of 179,000 participants from the UK Biobank with pregnancy experience and without depression or anxiety at baseline were included. Spontaneous miscarriage was defined by self-report from participants at enrollment or by International Classification of Diseases codes. The degree of social support was defined as the number of social support factors including living with a spouse or partner, participation in social activities, and confiding. Cox proportional hazards models were used to evaluate the joint association of spontaneous miscarriage and social support with the risks of depression and anxiety. RESULTS: During a median follow-up of 12.3 years, 4939 depression incidents and 5742 anxiety incidents were documented. For participants with 1, 2, and ≥3 spontaneous miscarriages, hazard ratios (95% confidence intervals) for depression were 1.10 (1.02-1.19), 1.31 (1.14-1.50), and 1.40 (1.18-1.67), respectively (P trend <.001), compared with participants without a history of spontaneous miscarriage, after adjustment for covariates. For anxiety, the hazard ratios (95% confidence intervals) were 1.07 (1.00-1.15), 1.04 (0.90-1.19), and 1.21 (1.02-1.44), respectively (P trend=.01). Moreover, we found that the risk of depression associated with a combination of spontaneous miscarriage and low degree of social support in later life was greater than the sum of the risks associated with each individual factor, indicating significant interactions on an additive scale (P interaction=.03). CONCLUSION: Spontaneous miscarriage is associated with higher risks of depression and anxiety, and the risk of depression is further increased when there is also low degree of social support.