Terahertz-triggered ultrafast nonlinear optical activities in two-dimensional centrosymmetric PtSe2.

The nonlinear mechanisms of polarization and optical fields can induce extensive responses in materials. In this study, we report on two kinds of nonlinear mechanisms in the topological semimetal PtSe2 crystal under the excitation of intense terahertz (THz) pulses, which are manipulated by the real and imaginary parts of the nonlinear susceptibility of PtSe2. Regarding the real part, the broken inversion symmetry of PtSe2 is achieved through a THz-electric-field polarization approach, which is characterized by second harmonic generation (SHG) measurements. The transient THz-laser-induced SHG signal occurs within 100 fs and recombines to the equilibrium state within 1 ps, along with a high signal-to-noise ratio (∼51 dB) and a high on/off ratio (∼102). Regarding the imaginary part, a nonlinear absorption change can be generated in the media. We reveal a THz-induced absorption enhancement in PtSe2 via nonlinear transmittance measurements, and the sheet conductivity can be modulated up to 42% by THz electric fields in our experiment. Therefore, the THz-induced ultrafast nonlinear photoresponse reveals the application potential of PtSe2 in photonic and optoelectronic devices in the THz technology.

Blood FOLR3 methylation dysregulations and heterogeneity in non-small lung cancer highlight its strong associations with lung squamous carcinoma.

BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for the vast majority of lung cancers. Early detection is crucial to reduce lung cancer-related mortality. Aberrant DNA methylation occurs early during carcinogenesis and can be detected in blood. It is essential to investigate the dysregulated blood methylation markers for early diagnosis of NSCLC. METHODS: NSCLC-associated methylation gene folate receptor gamma (FOLR3) was selected from an Illumina 850K array analysis of peripheral blood samples. Mass spectrometry was used for validation in two independent case-control studies (validation I: n = 2548; validation II: n = 3866). Patients with lung squamous carcinoma (LUSC) or lung adenocarcinoma (LUAD), normal controls (NCs) and benign pulmonary nodule (BPN) cases were included. FOLR3 methylations were compared among different populations. Their associations with NSCLC clinical features were investigated. Receiver operating characteristic analyses, Kruskal-Wallis test, Wilcoxon test, logistics regression analysis and nomogram analysis were performed. RESULTS: Two CpG sites (CpG_1 and CpG_2) of FOLR3 was significantly lower methylated in NSCLC patients than NCs in the discovery round. In the two validations, both LUSC and LUAD patients presented significant FOLR3 hypomethylations. LUSC patients were highlighted to have significantly lower methylation levels of CpG_1 and CpG_2 than BPN cases and LUAD patients. Both in the two validations, CpG_1 methylation and CpG_2 methylation could discriminate LUSC from NCs well, with areas under the curve (AUCs) of 0.818 and 0.832 in validation I, and 0.789 and 0.780 in validation II. They could also differentiate LUAD from NCs, but with lower efficiency. CpG_1 and CpG_2 methylations could also discriminate LUSC from BPNs well individually in the two validations. With the combined dataset of two validations, the independent associations of age, gender, and FOLR3 methylation with LUSC and LUAD risk were shown and the age-gender-CpG_1 signature could discriminate LUSC and LUAD from NCs and BPNs, with higher efficiency for LUSC. CONCLUSIONS: Blood-based FOLR3 hypomethylation was shown in LUSC and LUAD. FOLR3 methylation heterogeneity between LUSC and LUAD highlighted its stronger associations with LUSC. FOLR3 methylation and the age-gender-CpG_1 signature might be novel diagnostic markers for the early detection of NSCLC, especially for LUSC.

Adaptive Aromaticity in 18e Metallapentalenes.

Complexes with aromaticity in both the lowest singlet state (S0) and the lowest triplet state (T1) (denoted as adaptive aromaticity) are rare because according to Hückel's and Baird's rules, a species could be aromatic in either the S0 or T1 state in most cases. Thus, it is particularly challenging to design species with adaptive aromaticity. Previous reports on adaptive aromaticity were mainly focused on 16e metallapentalenes. Here, we demonstrate that 18e metallapentalenes could possess adaptive aromaticity supported by a set of aromaticity indices when the nitrido and imido ligands are introduced via density functional theory calculations. Further investigation suggests that the metal-carbon bond strength plays an important role in the S0 state aromaticity and the T1 state aromaticity could be attributed to spin electron localization. All these findings could be useful for the development of metallaaromatic chemistry.

Association between nontraditional lipid profiles and the severity of obstructive sleep apnea: A retrospective study.

BACKGROUND: Due to the significant role of dyslipidemia, cardiovascular diseases (CVDs) are very common in obstructive sleep apnea (OSA). Nontraditional lipid indices are considered to be a better predictive index for cardiovascular risk. Nevertheless, the association between nontraditional lipid profiles and the severity of OSA is not clear. METHODS: A retrospective study was proceeded on 635 patients. Subjects were diagnosed with OSA through polysomnography (PSG). The association between severe OSA and nontraditional lipid profiles [triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) ratio, total cholesterol (TC)/HDL-C ratio, low-density lipoprotein cholesterol (LDL-C)/HDL-C ratio, non-high-density lipoprotein cholesterol (non-HDL-C), atherogenic index (AI), and lipoprotein combine index (LCI)] was examined by utilizing the restricted cubic spline and multivariate logistic regression analysis. RESULTS: All nontraditional lipid indices had positive relationships with the severity of OSA. By multivariable adjustment, the per SD increment of the TG/HDL-C, TC/ HDL-C, LDL-C/HDL-C, non-HDL-C, AI, and LCI were significantly associated with 88%, 50%, 42%, 40%, 50%, and 125% higher risk for severe OSA respectively. Compared with the lowest tertiles, the adjusted ORs (95% CI) were 2.42 (1.57-3.75), 2.39 (1.53-3.73), 2.35 (1.52-3.64), 1.86 (1.21-2.86), 2.39 (1.53-3.73), and 2.23 (1.43-3.48) for the top tertiles of TG/HDL-C, TC/ HDL-C, LDL-C/HDL-C, non-HDL-C, AI, and LCI respectively. CONCLUSION: All nontraditional lipid indices had positive relationship with the severity of OSA. In addition, TG/HDL-C, TC/HDL-C, and AI had better performance than the other nontraditional lipid indices for predicting severe OSA. These findings could help to determine the risk of cardiovascular diseases and improve the dyslipidemia management of OSA patients.

Role of raphe magnus 5-HT1A receptor in increased ventilatory responses induced by intermittent hypoxia in rats.

BACKGROUND: Intermittent hypoxia induces increased ventilatory responses in a 5-HT-dependent manner. This study aimed to explore that effect of raphe magnus serotonin 1A receptor (5-HT1A) receptor on the increased ventilatory responses induced by intermittent hypoxia. METHODS: Stereotaxic surgery was performed in adult male rats, and acute and chronic intermittent hypoxia models were established after recovery from surgery. The experimental group received microinjections of 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) into the raphe magnus nucleus (RMg). Meanwhile, the control group received microinjections of artificial cerebrospinal fluid instead of 8-OH-DPAT. Ventilatory responses were compared among the different groups of oxygen status. 5-HT expressions in the RMg region were assessed by immunohistochemistry after chronic intermittent hypoxia. RESULTS: Compared with the normoxia group, the acute intermittent hypoxia group exhibited higher ventilatory responses (e.g., shorter inspiratory time and higher tidal volume, frequency of breathing, minute ventilation, and mean inspiratory flow) (P < 0.05). 8-OH-DPAT microinjection partly weakened these changes in the acute intermittent hypoxia group. Further, compared with the acute intermittent hypoxia group, rats in chronic intermittent hypoxia group exhibited higher measures of ventilatory responses after 1 day of intermittent hypoxia (P < 0.05). These effects peaked after 3 days of intermittent hypoxia treatment and then decreased gradually. Moreover, these changes were diminished in the experimental group. 5-HT expression in the RMg region increased after chronic intermittent hypoxia, which was consistent with the changing trend of ventilatory responses. While activation of the 5-HT1A receptor in the RMg region alleviated this phenomenon. CONCLUSIONS: The results indicate that RMg 5-HT1A receptor, via changing the expression level of 5-HT in the RMg region, is involved in the modulation of the increased ventilatory responses induced by intermittent hypoxia.

Relationship between body dissatisfaction, insufficient physical activity, and disordered eating behaviors among university students in southern China.

BACKGROUND: With an increasing incidence of obesity, the relationship between obesity and body image has become a hot research topic worldwide. From high school to university, young people experience changes in their social environment. University students have a high incidence of eating disorders and insufficient physical activity. The purpose of this study was to explore the relationship between body dissatisfaction, insufficient physical activity, and disordered eating behaviors among university students in southern China. METHODS: In total, 1296 university students aged 18-23 years were recruited for this study. The participants completed anthropometric measurements, the Physical Activity Rating scale-3 (PARS-3), and the Chinese-Dutch Eating Behavior Questionnaire (C-DEBQ). The ideal weight and silhouette were reported by university students using a questionnaire. RESULTS: Compared with men, young women had a higher level of body dissatisfaction. For men, body mass index (BMI; ß = 0.76, P <  0.01), physical activity score (ß = - 0.11, P <  0.01), and restrained eating score (ß = 0.10, P <  0.01) were the significant factors predictive of body dissatisfaction. For women, BMI (ß = 0.57, P <  0.01), muscle mass (ß = 0.12, P <  0.01), physical activity score (ß = - 0.11, P <  0.01), and restrained eating score (ß = 0.09, P <  0.01) were the significant factors predictive of body dissatisfaction. CONCLUSIONS: University students with high body dissatisfaction had lower physical activity scores and higher restrained eating scores. The data presented here highlight the impact of university students' body dissatisfaction on physical activity deficiency and disordered eating behaviors in China.

Biomimetic Injectable Hydrogel Based on Methacrylate-Modified Silk Fibroin Embedded with Kartogenin for Superficial Cartilage Regeneration.

The weak regeneration ability of chondrocytes is one of the main reasons that limit the therapeutic effect of clinical cartilage injury. Injectable hydrogels are potential scaffolds for cartilage tissue engineering with advantages such as minimally invasive surgery, porous structure, and drug sustained-release ability. At present, many biomaterials have been developed for the repair of deep cartilage defects. However, cartilage injury often begins on the surface, which requires us to propose a treatment strategy suitable for superficial cartilage injury repair. In this study, we fabricated a biomimetic injectable hydrogel based on methacrylate-modified silk fibroin (SilMA) embedded with kartogenin (KGN). The SilMA/KGN hydrogels have good biohistocompatibility and the ability to promote cartilage differentiation. In addition, SEM results show that it has a porous structure conducive to cell adhesion and proliferation. Most importantly, it has demonstrated remarkable superficial cartilage repair ability in vivo, showing potential in cartilage tissue engineering.

Cost-effective and natural-inspired lotus root/GelMA scaffolds enhanced wound healing via ROS scavenging, angiogenesis and reepithelialization.

Skin wounds, prevalent and fraught with complications, significantly impact individuals and society. Wound healing encounters numerous obstacles, such as excessive reactive oxygen species (ROS) production and impaired angiogenesis, thus promoting the development of chronic wound. Traditional clinical interventions like hemostasis, debridement, and surgery face considerable challenges, including the risk of secondary infections. While therapies designed to scavenge excess ROS and enhance proangiogenic properties have shown effectiveness in wound healing, their clinical adoption is hindered by high costs, complex manufacturing processes, and the potential for allergic reactions. Lotus root, distinguished by its natural micro and macro porous architecture, exhibits significant promise as a tissue engineering scaffold. This study introduced a novel scaffold based on hybridization of lotus root-inspired and Gelatin Methacryloyl (GelMA), verified with satisfactory physicochemical properties, biocompatibility, antioxidative capabilities and proangiogenic abilities. In vivo tests employing a full-thickness wound model revealed that these scaffolds notably enhanced micro vessel formation and collagen remodeling within the wound bed, thus accelerating the healing process. Given the straightforward accessibility of lotus roots and the cost-effective production of the scaffolds, the novel scaffolds with ROS scavenging, pro-angiogenesis and re-epithelialization abilities are anticipated to have clinical applicability for various chronic wounds.

Deferoxamine-Loaded Injectable Chitosan-Grafted Chlorogenic Acid/Oxidized Hyaluronic Acid Hybrid Hydrogel with Antibacterial, Anti-inflammatory, and Angiogenesis-Promoting Properties for Diabetic Wound Repair.

Diabetic chronic wounds are notoriously difficult to heal as a result of their susceptibility to infection. To address this issue, we constructed an innovated and adaptable solution in the form of injectable chitosan (CS) hydrogel, denoted as CCOD, with enhanced antibacterial and anti-inflammatory properties. This hydrogel is created through a Schiff base reaction that combines chitosan-grafted chlorogenic acid (CS-CGA) and oxidized hyaluronic acid (OHA) with deferoxamine (DFO) as a model drug. The combination of CS and CGA has demonstrated excellent antibacterial and anti-inflammatory properties, while grafting played a pivotal role in making these positive effects stable. These unique features make it possible to customize injectable hydrogel and fit any wound shape, allowing for more effective and personalized treatment of complex bacterial infections. Furthermore, the hydrogel system is not only effective against inflammation and bacterial infections but also possesses antioxidant and angiogenic abilities, making it an ideal solution for the repair of chronic wounds that have been previously thought of as unmanageable.

Prediction of Prognosis and Immunotherapy Response of Gastric Cancer Based on Glutamine Metabolism-Related Genes.

BACKGROUND: Reprogramming of glutamine metabolism in Gastric Cancer (GC) can significantly affect the tumor immune microenvironment and immunotherapy. This study examines the role of glutamine metabolism in the microenvironment and prognosis of gastric cancer. METHODS: We obtained gene expression data and clinical information of patients from the TCGA database. The patients were divided into two metabolic subtypes based on consistent clustering. A prognostic risk model containing three glutamine metabolism-related genes (GMRGs) was developed using Lasso-Cox. It was validated by the GEO validation cohort. Additionally, the immune microenvironment composition of the highand low-risk groups was assessed using ESTIMATE, CIBERSORT, and ssGSEA. Drug sensitivity analysis was conducted using the "oncoPredict" R package. RESULTS: We outlined the distinct clinical characteristics of two subtypes and developed a prognostic risk model. The high-risk group has a poorer prognosis due to an increased expression of immune checkpoints and immunosuppressive cellular infiltration. Our analysis, which included Cox risk regression, ROC curves, and nomogram, demonstrated that this risk model is an independent prognostic factor. The TIDE score was higher in the high-risk group than in the low-risk group. Additionally, the high-risk group did not respond well to chemotherapeutic drug treatment. CONCLUSION: This study shows that modelling glutamine metabolism is a good predictor of prognosis and immunotherapy efficacy in gastric cancer. Thus, we can better understand the role of glutamine metabolism in the development of cancer and use these insights to develop more targeted and effective treatments.

Natural pachypodol integrated, lung targeted and inhaled lipid nanomedicine ameliorates acute lung injury via anti-inflammation and repairing lung barrier.

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a high-mortality disease caused by multiple disorders such as COVID-19, influenza, and sepsis. Current therapies mainly rely on the inhalation of nitric oxide or injection of pharmaceutical drugs (e.g., glucocorticoids); however, their toxicity, side effects, or administration routes limit their clinical application. In this study, pachypodol (Pac), a hydrophobic flavonol with anti-inflammatory effects, was extracted from Pogostemon cablin Benth and intercalated in liposomes (Pac@liposome, Pac-lipo) to improve its solubility, biodistribution, and bioavailability, aiming at enhanced ALI/ARDS therapy. Nanosized Pac-lipo was confirmed to have stable physical properties, good biodistribution, and reliable biocompatibility. In vitro tests proved that Pac-lipo has anti-inflammatory property and protective effects on endothelial and epithelial barriers in lipopolysaccharide (LPS)-induced macrophages and endothelial cells, respectively. Further, the roles of Pac-lipo were validated on treating LPS-induced ALI in mice. Pac-lipo showed better effects than did Pac alone on relieving ALI phenotypes: It significantly attenuated lung index, improved pulmonary functions, inhibited cytokine expression such as TNF-α, IL-6, IL-1ß, and iNOS in lung tissues, alleviated lung injury shown by HE staining, reduced protein content and total cell number in bronchoalveolar lavage fluid, and repaired lung epithelial and vascular endothelial barriers. As regards the underlying mechanisms, RNA sequencing results showed that the effects of the drugs were associated with numerous immune- and inflammation-related signaling pathways. Molecular docking and western blotting demonstrated that Pac-lipo inhibited the activation of the TLR4-MyD88-NF-κB/MAPK signaling pathway. Taken together, for the first time, our new drug (Pac-lipo) ameliorates ALI via inhibition of TLR4-MyD88-NF-κB/MAPK pathway-mediated inflammation and disruption of lung barrier. These findings may provide a promising strategy for ALI treatment in the clinic.

Topical treatment of tyrosine kinase 2 inhibitor through borneol-embedded hydrogel: Evaluation for preventive, therapeutic, and Recurrent management of psoriasis.

Psoriasis, an immune-mediated inflammatory skin disorder characterized by a chronically relapsing-remitting course, continues to be primarily managed through topical therapy. While oral administration of tyrosine kinase 2 inhibitors (TYK2i) stands as an effective approach for psoriasis treatment, the potential efficacy of topical application of TYK2i remains unexplored. Herein, the carbomer/alginic acid hydrogel is embedded with borneol (BO) as a new topical carrier of TYK2i for achieving enhanced transdermal permeation and anti-psoriasis efficacy. The hydrogel system, i.e., TYK2i-BO-gel, exhibits significantly improved preventative and therapeutic effects in mice models of psoriasiform dermatitis, as evidenced by phenotypical images, psoriasis severity score index (PSI), histology, immunohistochemical staining, and PCR analysis. Remarkably, TYK2i-BO-gel outperforms conventional topical corticosteroid therapy by significantly preventing psoriatic lesion recurrence as measured by a nearly 50 % reduction in ear thickness changes (p < 0.0001), PSI (p < 0.0001) and epidermal thickness (p < 0.05). Moreover, a strengthened anti-inflammatory effect caused by TYK2i-BO-gel is seen in a human skin explant model, implying its potential application for human patients. With the addition of BO, the TYK2i-BO-gel not only increases skin permeability but also inhibits the expression of antimicrobial peptides in keratinocytes and facilitates the anti-Th17 response of TYK2i with suppressed activation of STAT3. Therefore, this work represents the accessibility and effectiveness of TYK2i-BO-hydrogel as a new topical formulation for anti-psoriasis management and shows great potential for clinical application.

Ferroptosis participated in inhaled polystyrene nanoplastics-induced liver injury and fibrosis.

The emerging contaminant nanoplastics (NPs) have received considerable attention. Due to their tiny size and unique colloidal properties, NPs could more easily enter the body and cross biological barriers with inhalation exposure. While NPs-induced hepatotoxicity has been reported, the hepatic impact of inhaled NPs was still unknown. To close this gap, a 40 nm polystyrene NPs (PS-NPs) inhalation exposure mice model was developed to explore the hepatotoxicity during acute (1 week), subacute (4 weeks), and subchronic period (12 weeks), with four exposure doses (0, 16, 40, and 100 µg/day). Results showed that inhaled PS-NPs caused a remarkable increase of ALT, AST, and ALP with a decrease of CHE, indicating liver dysfunction. Various histological abnormalities and significantly higher levels of inflammation in a dose- and time-dependent manner were observed. Moreover, after 4 weeks and 12 weeks of exposure, Masson staining and upregulated expression of TGF-ß, α-SMA, and Col1a1 identified that inhaled PS-NPs exposure triggered the progression of liver fibrosis with the exposure time prolonged. From the mechanistic perspective, transcriptome analysis revealed that ferroptosis was involved in PS-NPs-induced liver hepatotoxicity, and key features of ferroptosis were detected, including persistent oxidative stress, iron overload, increased LPO, mitochondria damage, and the expression changes of GPX4, TFRC, and Ferritin. And in vitro and in vivo recovery tests showed that ferroptosis inhibitor Fer-1 treatment alleviated liver injury and fibrosis. The above results confirmed the critical role of ferroptosis in PS-NPs-induced hepatotoxicity. Furthermore, to better conclude our findings and understand the mechanistic causality within it, an adverse outcome pathway (AOP) framework was established. In total, this present study conducted the first experimental assessment of inhalation exposure to PS-NPs on the liver, identified that continuous inhaled PS-NPs could cause liver injury and fibrosis, and PS-NPs- ferroptosis provided a novel mechanistic explanation.

FAM72A degrades UNG2 through the GID/CTLH complex to promote mutagenic repair during antibody maturation.

A diverse antibody repertoire is essential for humoral immunity. Antibody diversification requires the introduction of deoxyuridine (dU) mutations within immunoglobulin genes to initiate somatic hypermutation (SHM) and class switch recombination (CSR). dUs are normally recognized and excised by the base excision repair (BER) protein uracil-DNA glycosylase 2 (UNG2). However, FAM72A downregulates UNG2 permitting dUs to persist and trigger SHM and CSR. How FAM72A promotes UNG2 degradation is unknown. Here, we show that FAM72A recruits a C-terminal to LisH (CTLH) E3 ligase complex to target UNG2 for proteasomal degradation. Deficiency in CTLH complex components result in elevated UNG2 and reduced SHM and CSR. Cryo-EM structural analysis reveals FAM72A directly binds to MKLN1 within the CTLH complex to recruit and ubiquitinate UNG2. Our study further suggests that FAM72A hijacks the CTLH complex to promote mutagenesis in cancer. These findings show that FAM72A is an E3 ligase substrate adaptor critical for humoral immunity and cancer development.

Tomato based gelatin methacryloyl hydrogel as an effective natural and low-cost scaffold for accelerative wound healing.

Oxidative stress and infection are the main reasons for postponement of wound healing rate. They can potentially lead to serious inflammation and eventually lead to a longer and more painful recovery phase. Although wound dressings based on synthetic materials with antioxidative property have been proved to exhibit remarkable effect in controlling ROS level and improving wound healing, issues, such as high cost in raw materials, complicated procedures, usage of various toxic additives, and potential allergies, have significantly confined further clinical applications. In this study, a novel type of tissue engineering scaffold, based on tomatoes (Solanum lycopersicon) and gelatin methacryloyl (GelMA), was prepared via facile lyophilization and photo cross-link method (SL/GelMA). By taking advantages of various antioxidative components, such as carotenoids, flavonoids, phenolic acids, vitamin E, and vitamin C in tomatoes, SL/GelMA can effectively regulate ROS level, relieve the oxidative stress in wound bed, promote cell migration and angiogenesis, contribute to collagen deposition, and thus accelerate the rate of wound enclosure. Along with its high biocompatibility and low allergic potential, we believe that the food-derived wound dressing with facile preparation method, easy accessibility, and high cost-effectiveness can be translated for clinical treatments of various chronic wounds.

Integrated microbiome-metabolome-genome axis data of Laiwu and Lulai pigs.

Excessive fat deposition can trigger metabolic diseases, and it is crucial to identify factors that can break the link between fat deposition and metabolic diseases. Healthy obese Laiwu pigs (LW) are high in fat content but resistant to metabolic diseases. In this study, we compared the fecal microbiome, fecal and blood metabolome, and genome of LW and Lulai pigs (LU) to identify factors that can block the link between fat deposition and metabolic diseases. Our results show significant differences in Spirochetes and Treponema, which are involved in carbohydrate metabolism, between LW and LU. The fecal and blood metabolome composition was similar, and some anti-metabolic disease components of blood metabolites were different between the two breeds of pigs. The predicted differential RNA is mainly enriched in lipid metabolism and glucose metabolism, which is consistent with the functions of differential microbiota and metabolites. The down-regulated gene RGP1 is strongly negatively correlated with Treponema. Our omics data would provide valuable resources for further scientific research on healthy obesity in both human and porcine.

Autoantibodies of inflammatory cytokines as serum biomarkers in OSA patients.

As many as 90% of patients with obstructive sleep apnea (OSA) may be undiagnosed. It is necessary to explore the potential value of autoantibodies against CRP, IL-6, IL-8 and TNF-α in the diagnosis of OSA. ELISA was performed to detect the level of autoantibodies against CRP, IL-6, IL-8 and TNF-α in sera from 264 OSA patients and 231 normal controls (NCs). The expression level of autoantibodies against CRP, IL-6 and IL-8 in OSA were significantly higher than that in NC while the level of anti-TNF-α was lower in OSA than that in NC. The per SD increment of anti-CRP, anti-IL-6 and anti-IL-8 autoantibodies were significantly associated with a 430%, 100% and 31% higher risk for OSA, respectively. The AUC of anti-CRP was 0.808 (95% CI: 0.771-0.845) when comparing OSA with NC, while the AUC increased to 0.876 (95% CI: 0.846-0.906) combining four autoantibodies. For discrimination of severe OSA versus NC and non-severe OSA versus NC, the AUC for four autoantibodies combination was 0.885 (95% CI: 0.851-0.918) and 0.876 (95% CI: 0.842-0.913). This study revealed the association between autoantibodies against inflammatory factors and OSA, and the combination of autoantibodies against CRP, IL-6, IL-8 and TNF-α may function as novel biomarker for monitoring the presence of OSA.

A remarkably diverse and well-organized virus community in a filter-feeding oyster.

BACKGROUND: Viruses play critical roles in the marine environment because of their interactions with an extremely broad range of potential hosts. Many studies of viruses in seawater have been published, but viruses that inhabit marine animals have been largely neglected. Oysters are keystone species in coastal ecosystems, yet as filter-feeding bivalves with very large roosting numbers and species co-habitation, it is not clear what role they play in marine virus transmission and coastal microbiome regulation. RESULTS: Here, we report a Dataset of Oyster Virome (DOV) that contains 728,784 nonredundant viral operational taxonomic unit contigs (≥ 800 bp) and 3473 high-quality viral genomes, enabling the first comprehensive overview of both DNA and RNA viral communities in the oyster Crassostrea hongkongensis. We discovered tremendous diversity among novel viruses that inhabit this oyster using multiple approaches, including reads recruitment, viral operational taxonomic units, and high-quality virus genomes. Our results show that these viruses are very different from viruses in the oceans or other habitats. In particular, the high diversity of novel circoviruses that we found in the oysters indicates that oysters may be potential hotspots for circoviruses. Notably, the viruses that were enriched in oysters are not random but are well-organized communities that can respond to changes in the health state of the host and the external environment at both compositional and functional levels. CONCLUSIONS: In this study, we generated a first "knowledge landscape" of the oyster virome, which has increased the number of known oyster-related viruses by tens of thousands. Our results suggest that oysters provide a unique habitat that is different from that of seawater, and highlight the importance of filter-feeding bivalves for marine virus exploration as well as their essential but still invisible roles in regulating marine ecosystems. Video Abstract.

Blocking TGF-ß Expression Attenuates Tumor Growth in Lung Cancers, Potentially Mediated by Skewing Development of Neutrophils.

In the tumor microenvironment (TME), cells secrete a cytokine known as transforming growth factor-ß (TGF-ß), which polarizes tumor-associated neutrophils (TANs) towards a protumor phenotype. In this work, C57BL/6 mice with TGF-ß1 gene knocked out selectively in myofibroblasts receive orthotopic implantation of Lewis lung carcinoma (LLC). Then, TANs' differentiation and tumor growth are studied both in vivo and in vitro, to examine the potential effects of TGF-ß levels in TME on neutrophil polarization and cancer progression. Possible results are anticipated and discussed from various aspects. Though tumor suppression via inhibition of TGF-ß signaling has been widely studied in this field, this study is the first to present a detailed experimental design for evaluating the potential antitumor effects of blocking TGF-ß expression. This work provides a creative approach for cancer treatment targeting specific cytokines, and the experimental design presented here may apply to future research on other cytokines, promoting the development of novel cancer-treating strategies.

Hydrogel Development for Rotator Cuff Repair.

Rotator cuff tears (RCTs) are common in shoulder disease and disability. Despite significant advances in surgical repair techniques, 20-70% of patients still have postoperative rotator cuff dysfunction. These functional defects may be related to retear or rotator cuff quality deterioration due to tendon retraction and scar tissue at the repair site. As an effective delivery system, hydrogel scaffolds may improve the healing of RCTs and be a useful treatment for irreparable rotator cuff injuries. Although many studies have tested this hypothesis, most are limited to laboratory animal experiments. This review summarizes differences in hydrogel scaffold construction, active ingredients, and application methods in recent research. Efforts to determine the indications of hydrogel scaffolds (with different constructions and cargos) for various types of RCTs, as well as the effectiveness and reliability of application methods and devices, are also discussed.