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Context Yi-Qi Cong-Ming (YQCM) decoction has been widely used to prevent age-related hearing loss (ARHL), the most prevalent neurodegenerative disease in the elderly.Objective To explore the mechanism of YQCM decoction in the treatment of ARHL.Materials and methods The chemical constituents of YQCM were screened from the Traditional Chinese Medicine Systems Pharmacology Database. Potential targets of YQCM against ARHL were predicted by DrugBank, GeneCards, and OMIM database. Protein-protein network and enrichment analysis were used for exploring possible molecular mechanisms. Molecular docking and an in vitro model of ARHL by exposing auditory cells with 100 μM H2O2 for 3 h were applied. Cell viability and mitochondrial membrane potential (ΔΨM) were detected by CCK-8 and high-content analysis. γH2AX and cleaved caspase-3 were detected by Western blot.Results The main compounds have good affinities with hub targets, especially AKT1, PTGS2, and CASP3. GO and KEGG analysis showed that the main biological process and key targets were related to negative regulation of the apoptotic process. H2O2 treatment could reduce the cell viability by 68% and impaired ΔΨM, while 90 μg/mL YQCM pre-treatment could restore the cell viability by 97.45% and increase ΔΨM (2-fold higher). YQCM pre-treatment also reduced γH2AX and cleaved caspase-3 protein levels.Conclusions Our study suggested that YQCM prevents ARHL by modulating the apoptosis process in auditory hair cells. Moreover, this study proved that bioinformatics analysis combined with molecular docking and cell model is a promising method to explore other possible pharmacological interventions of ARHL.

Pyrimidine nucleosides (PN) are abundant in mammalian milk and mainly involved in glycogen deposition and lipid metabolism. To investigate the effects of maternal supplementation with pyrimidine nucleoside on glucose, fatty acids (FAs), and amino acids (AAs) metabolism in neonatal piglets. Forty pregnant sows were randomly assigned into the control (CON) group (fed a basal diet, n = 20) or the PN group (fed a basal diet supplemented with PN at 150 g/t, n = 20). Litter size, born alive and birth litter weight were recorded. The serum and placenta of sows, and jejunum and liver of neonatal piglets were sampled. The results indicated that supplementing sow diets with PN decreased birth mortality and increased the birth weight of piglets (P

With the increasing demand for high-quality pork, more nutritional substances have been studied for the regulation of meat quality. Zero-dimensional fullerenes (C60) can modulate the biological behavior of a variety of cell lines and animals. In this study, we report the biological effects of C60 on finishing pigs at different concentrations. A total of 24 barrows (Duroc × Large White × Landrace), with an average body weight of 21.01 ± 0.98 kg, were divided into 3 groups and each treated daily with C60 (100 or 200 mg per kg feed) or a control diet until the end of the experiment. Our results showed that dietary C60 supplementation improved flesh color, marbling scores, and flavor amino acid contents of longissimus dorsi (LD) of growing-finishing pigs (P

Sodium aescinate (SA) is often used for intravenous (IV) injection owing to its anti-inflammatory, anti-exudative, increasing venous tension, improving blood circulation and reducing swelling activities. However, the clinical application of SA is limited by strong irritation, short half-life and low bioavailability. To overcome these defects, we intended to modify SA by encapsualing it with liposomes . SA was mixed with a proper amount of phospholipid and lyophilized to prepare the liposome of sodium aescinate for injection (SA-Lip-I). Its physical properties, cumulative release and dilution stability were evaluated in vitro. Its pharmacodynamic characteristics were evaluated. Safety of SA-Lip-I was evaluated in terms of hemolysis, IV irritation and acute toxicity. The mean particle size of SA-Lip-I was 117.33±0.95 nm, polydispersity index (PDI) was 0.140±0.017, Zeta potential was -30.34±0.23 mv, The cumulative release of SA-Lip at 12 h was more than 80%, which met the release requirements of nanoparticles. SA-Lip-I was well stable in the four mediators and met the clinical medication requirements. In addition, SA-Lip-I had better efficacy than the SA-I and has a significant difference. Furthermore, SA-Lip-I did not induce hemolysis at 37°C, and produced by far milder venous irritation as compared with SA-I. In addition, LD50 of SA-Lip-I was 2.12 fold that of the commercial SA-I, with no obvious side effects.The modified SA-Lip-I is a promising preparation which can reduce the irritation and toxic side effects, improve the treatment effect to a certain extent, but greatly alleviate pain of the patient during treatment, achieving the optimal curative effect.

Biomass energy can reduce the consumption of fossil fuels and reduce environmental pollution. The project site selection affects the production efficiency and economic benefits. Firstly, this study proposes a macro-site selection decision framework for biomass cogeneration considering carbon emission reduction. Secondly, this paper innovatively uses Nash equilibrium as the coordination goal, and introduces Game Theory to determine the optimal combination weight of Best-Worst Method (BWM) and Criteria Importance Though Intercriteria Correlation (CRITIC). Further thinking is needed to improve the comprehensive closeness measurement method, establish a Technique for Order Preference by Similarity to an Ideal Solution and Grey Relational Analysis (TOPSIS-GRA) site selection model that reflects distance and curve shape, and sort the plans. And then explore the barriers to improving the site selection environment. Finally take five cities in China as an example. The feasibility and the stability of the site selection decision-making framework in practical applications are verified by comparative analysis and weight sensitivity analysis. The results show that carbon emission is the primary barrier factor in the criterion layer. In the sub-criterion layer, transportation costs, carbon emission pressure, carbon benefits, industrial policies, and heating rate are the common obstacle factors in each region. To promote the long-term healthy development of the project, this study provides a theoretical reference for the new construction and expansion of biomass cogeneration projects, and has guiding significance for improving the location suitability of the project.

Abstract Background Avian influenza A H7N9 emerged in 2013, threatening public health and causing acute respiratory distress syndrome, and even death, in the human population. However, the underlying mechanism by which H7N9 virus causes human infection remains elusive. Methods Herein, we infected A549 cells with H7N9 virus for different times and assessed tripartite motif-containing protein 46 (TRIM46) expression. To determine the role of TRIM46 in H7N9 infection, we applied lentivirus-based TRIM46 short hairpin RNA sequences and overexpression plasmids to explore virus replication, and changes in type I interferons and interferon regulatory factor 3 (IRF3) phosphorylation levels in response to silencing and overexpression of TRIM46. Finally, we used Co-immunoprecipitation and ubiquitination assays to examine the mechanism by which TRIM46 mediated the activity of TANK-binding kinase 1 (TBK1). Results Type I interferons play an important role in defending virus infection. Here, we found that TRIM46 levels were significantly increased during H7N9 virus infection. Furthermore, TRIM46 knockdown inhibited H7N9 virus replication compared to that in the control group, while the production of type I interferons increased. Meanwhile, overexpression of TRIM46 promoted H7N9 virus replication and decrease the production of type I interferons. In addition, the level of phosphorylated IRF3, an important interferon regulatory factor, was increased in TRIM46-silenced cells, but decreased in TRIM46 overexpressing cells. Mechanistically, we observed that TRIM46 could interact with TBK1 to induce its K48-linked ubiquitination, which promoted H7N9 virus infection. Conclusion Our results suggest that TRIM46 negatively regulates the human innate immune response against H7N9 virus infection.

Abstract Background Patients with systemic lupus erythematosus (SLE) are highly susceptible to infection and cardiovascular events, suggesting that chronic antigenic stimulation may accelerate premature aging in SLE patients. Premature aging in SLE is often accompanied with the expansion of cytotoxic CD4 + CD28−T cells. Damage caused by CD4 + CD28− T cells enhances the progressive aging of the tissue function and loss of organism’s fitness. The high serum level of IL-15 has been implicated in the pathogenesis of SLE, but its role in CD4 + CD28−T cell-mediated cytotoxicity in nephritic SLE remains unclear. The aim of this study was to investigate the effect of IL-15 on functional properties and associated renal damage of cytotoxic CD4 + CD28− T cell in lupus nephritis (LN). Results Flow cytometry showed that the number of circulating innate-like CD4 + CD28− T cells was increased in patients with nephritic SLE. Immunofluorescence showed CD4 + CD28− T cell infiltration in the kidney of LN patients, which was correlated with multiple clinicopathological features including estimated glomerular filtration rate (eGFR), proteinuria, the proportion of glomerulosclerosis and the degree of renal chronicity. In addition, a high level of IL-15 and IL15-expressing macrophage infiltration was detected in the periglomerular and intraglomerular tissues of LN patients, which enhanced the innate features, cytokine secretion and migratory capability of CD4 + CD28− T cells, and finally exerted direct TCR-independent cytotoxicity on glomerular endothelial cells in an IL-15-dependent manner in vitro. Conclusion Our study demonstrated that excessive IL-15 potentially promoted cytotoxic CD4 + CD28− T cell-mediated renal damage in LN. This finding may provide new insights into the potential association of premature aging and tissue damage in LN.

The recent development of imaging and sequencing technologies enables systematic advances in the clinical study of lung cancer. Meanwhile, the human mind is limited in effectively handling and fully utilizing the accumulation of such enormous amounts of data. Machine learning-based approaches play a critical role in integrating and analyzing these large and complex datasets, which have extensively characterized lung cancer through the use of different perspectives from these accrued data. In this review, we provide an overview of machine learning-based approaches that strengthen the varying aspects of lung cancer diagnosis and therapy, including early detection, auxiliary diagnosis, prognosis prediction, and immunotherapy practice. Moreover, we highlight the challenges and opportunities for future applications of machine learning in lung cancer.

Abstract We study the influence of parameter $$\alpha $$ α on the optical features of Schwarzschild-MOG black holes with different thin accretions in scalar-tensor-vector gravity. As $$\alpha $$ α increases from 0, the radii of the event horizon, photon sphere, and observed shadow increase in comparison with the Schwarzschild black hole. We constrain the parameter $$\alpha $$ α with the experimental data reported by the Event Horizon Telescope Collaboration for M87 $$^{*}$$ ∗ and Sagittarius A $$^{*}$$ ∗ . In the situation of spherical accretions, we unveil that the parameter $$\alpha $$ α has a positive effect on the shadow size but a negative effect on the observed specific intensities. Considering that the Schwarzschild-MOG black hole is surrounded by an optical and geometrically thin accretion disk, we find that the total observed specific intensities are mainly contributed by the direct emissions, while the photon rings and lensed rings provide small contributions. It is also found that with the increase of $$\alpha $$ α , the black hole shadow expands, the photon rings and lensed rings become larger and thicker. Besides, we emphasize that the boundary of the observed shadow cast by the aim black hole in the disk accretion scenario is determined by the direct emissions rather than the photon ring emissions. Consequently, we unveil that there is a linear relationship involving the critical impact parameter and the starting point of the direct emissions. This finding helps to use the experimental results of the Event Horizon Telescope to infer the critical impact parameter and to test General Relativity.

The application of surface texture technology can cut down the friction of journal bearing in internal combustion engines, so as to reduce energy consumption and improve effective. A three-dimensional simulation model of the lubrication characteristics is established so as to investigate the effect of surface texture on the load capacity of journal bearing. The accuracy of the simulation model is verified by comparing with the test. On this basis, through the establishment of a two-dimensional texture unit lubrication characteristics simulation model, the influence law of four different texture shapes, such as triangle, arc, rectangle and trapezoid, and typical structural parameters on the load capacity of the load capacity is studied. Finally, a three-dimensional simulation model of lubrication characteristics of the rectangular textured journal bearing is established. Based on this model, the effect of texture distribution position on the load capacity is studied. It shows that the position of the texture will affect the load capacity. The maximum pressure and load capacity are increased when the texture is in the wedge gap convergence region, but they will decrease when in the divergence region.

The application of surface texture technology can cut down the friction of journal bearing in internal combustion engines, so as to reduce energy consumption and improve effective. A three-dimensional simulation model of the lubrication characteristics is established so as to investigate the effect of surface texture on the load capacity of journal bearing. The accuracy of the simulation model is verified by comparing with the test. On this basis, through the establishment of a two-dimensional texture unit lubrication characteristics simulation model, the influence law of four different texture shapes, such as triangle, arc, rectangle and trapezoid, and typical structural parameters on the load capacity of the load capacity is studied. Finally, a three-dimensional simulation model of lubrication characteristics of the rectangular textured journal bearing is established. Based on this model, the effect of texture distribution position on the load capacity is studied. It shows that the position of the texture will affect the load capacity. The maximum pressure and load capacity are increased when the texture is in the wedge gap convergence region, but they will decrease when in the divergence region.

Abstract Surgical resection is the main treatment option for most solid tumors, yet cancer recurrence after surgical resection remains a significant challenge in cancer therapy. Recent advances in cancer immunotherapy are enabling radical cures for many tumor patients, but these technologies remain challenging to apply because of side effects related to uncontrollable immune system activation. Here, we develop far-red light-controlled immunomodulatory engineered cells (FLICs) that we load into a hydrogel scaffold, enabling the precise optogenetic control of cytokines release (IFN-β, TNF-α, and IL-12) upon illumination. Experiments with a B16F10 melanoma resection mouse model show that FLICs-loaded hydrogel implants placed at the surgical wound site achieve sustainable release of immunomodulatory cytokines, leading to prevention of tumor recurrence and increased animal survival. Moreover, the FLICs-loaded hydrogel implants elicit long-term immunological memory that prevents against tumor recurrence. Our findings illustrate that this optogenetic perioperative immunotherapy with FLICs-loaded hydrogel implants offers a safe treatment option for solid tumors based on activating host innate and adaptive immune systems to inhibit tumor recurrence after surgery. Beyond extending the optogenetics toolbox for immunotherapy, we envision that our optogenetic-controlled living cell factory platform could be deployed for other biomedical contexts requiring precision induction of bio-therapeutic dosage.

Abstract Objective Thyroid carcinoma (TC) is the most common endocrine tumor in the human body. Papillary thyroid carcinoma (PTC) accounts for more than 80% of thyroid cancers. Accurate prediction of elderly PTC can help reduce the mortality of patients. We aimed to construct a nomogram predicting cancer-specific survival (CSS) in elderly patients with PTC. Methods Patient information was downloaded from the Surveillance, Epidemiology, and End Results (SEER) program. Univariate and multivariate Cox regression models were used to screen the independent risk factors for patients with PTC. The nomogram of elderly patients with PTC was constructed based on the multivariate Cox regression model. We used the concordance index (C-index), the area under the receiver operating characteristic curve (AUC) and the calibration curve to test the accuracy and discrimination of the prediction model. Decision curve analysis (DCA) was used to test the clinical value of the model. Results A total of 14,138 elderly patients with PTC were included in this study. Patients from 2004 to 2015 were randomly divided into a training set (N = 7379) and a validation set (N = 3141), and data from 2016 to 2018 were divided into an external validation set (N = 3618). Proportional sub-distribution hazard model showed that age, sex, tumor size, histological grade, TNM stage, surgery and chemotherapy were independent risk factors for prognosis. In the training set, validation set and external validation set, the C-index was 0.87(95%CI: 0.852–0.888), 0.891(95%CI: 0.866–0.916) and 0.931(95%CI:0.894–0.968), respectively, indicating that the nomogram had good discrimination. Calibration curves and AUC suggest that the prediction model has good discrimination and accuracy. Conclusions We constructed a new nomogram to predict CSS in elderly patients with PTC. Internal cross-validation and external validation indicate that the model has good discrimination and accuracy. The predictive model can help doctors and patients make clinical decisions.

The genetic bases of yak adaptations to extreme conditions remains elusive. This study compares yak and cattle at a genomic and transcriptomic level, revealing a new type of endothelial cell and candidate genes related with elastic fiber formation in yak lungs that might contribute to high altitude adaptation.

BackgroundOxidative stress plays a significant role in the tumorigenesis and progression of tumors. We aimed to develop a prognostic signature using oxidative stress-related genes (ORGs) to predict clinical outcome and provide light on the immunotherapy responses of clear cell renal cell carcinoma (ccRCC).MethodsThe information of ccRCC patients were collected from the TCGA and the E-MTAB-1980 datasets. Univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) were conducted to screen out overall survival (OS)-related genes. Then, an ORGs risk signature was built by multivariate Cox regression analyses. The performance of the risk signature was evaluated with Kaplan-Meier (K-M) survival. The ssGSEA and CIBERSORT algorithms were performed to evaluate immune infiltration status. Finally, immunotherapy responses was analyzed based on expression of several immune checkpoints.ResultsA prognostic 9-gene signature with ABCB1, AGER, E2F1, FOXM1, HADH, ISG15, KCNMA1, PLG, and TEK. The patients in the high risk group had apparently poor survival (TCGA: p < 0.001; E-MTAB-1980: p < 0.001). The AUC of the signature was 0.81 at 1 year, 0.76 at 3 years, and 0.78 at 5 years in the TCGA, respectively, and was 0.8 at 1 year, 0.82 at 3 years, and 0.83 at 5 years in the E-MTAB-1980, respectively. Independent prognostic analysis proved the stable clinical prognostic value of the signature (TCGA cohort: HR = 1.188, 95% CI =1.142-1.236, p < 0.001; E-MTAB-1980 cohort: HR =1.877, 95% CI= 1.377-2.588, p < 0.001). Clinical features correlation analysis proved that patients in the high risk group were more likely to have a larger range of clinical tumor progression. The ssGSEA and CIBERSORT analysis indicated that immune infiltration status were significantly different between two risk groups. Finally, we found that patients in the high risk group tended to respond more actively to immunotherapy.ConclusionWe developed a robust prognostic signature based on ORGs, which may contribute to predict survival and guide personalize immunotherapy of individuals with ccRCC.

The objective of this study was to investigate the colonic microbiome compositions and immune response and reveal their correlations in weaned piglets fed with garlic essential oil (GEO). Twelve 21-day-old crossbred piglets with the same parity and similar weight (BW = 7.07 ± 0.37 Kg) were randomly divided into control and experimental groups based on BW and sex, which fed either a basal diet (CON group), or a basal diet supplemented with 1.5 g/kg GEO (GEO group). UHPLC-QE-MS showed the main component of GEO were belonged to carbohydrates, organic acid, flavonoids, phenylpropanoids and terpenoids. GEO decreased serum IL-1β, IL-8 content and the down-regulated mRNA expression of IFN-γ, TLR2 in jejunal mucosa but increased serum IgG, IL-4 content and up-regulated the mRNA expression of IL-4, IL-1β, TNF-α in ileal mucosa. What's more, the metagenomic analysis demonstrated that GEO increased the abundance of Bacteroidetes, Euryarchaeota and Spirochaetes, while decreased the abundance of Firmicutes and Actinobacteria at Phylum level and Selenomonas_boris, Selenomonadaceae_bacterium_DSM_108025, Clostridiales_bacterium and Phascolarctobacterium_succinatutens at species level. Notably, the main function pathway of virulence factor (VFDB) enriched in GEO group were Fibronection-binding protein, Zn++ metallophrotease and Capsular polysaccharide, while the main function pathway of VFDB enriched in CON group were heme biosynthesis, Lap and FeoAB. Spearman correlation analysis indicated the Spirochaetes had a positive association with IL-6 and IL-4. Acinobacteria was positively correlated with IL-1β, while negative with the IL-6; In addition, Euryarchaeota had a positive correlation with IL-4, but a negative correlation with IL-1β; Tenericutes was negative with IL-8; Phascolarcolarctobacterium_succinatutens and was negative with IL-6; Ruminococcaceae_bacterium was negative with TNF-α. While Selenomonadaceae_bacterium_DSM_108025 had a positive correlation with IL-8. In conclusion, our results uncovered that immune regulation effects of GEO may be associated with the microbiome compositions in response to GEO.

Summary: Bidirectional communication between the developing conceptus and endometrium is essential for pregnancy recognition and establishment in ruminants. We dissect the transcriptomic dynamics of sheep conceptus and corresponding endometrium at pre- and peri-implantation stages using single-cell RNA sequencing. Spherical blastocysts contain five cell types, with 68.62% trophectoderm cells. Strikingly, elongated conceptuses differentiate into 17 cell types, indicating dramatic cell fate specifications. Cell-type-specific gene expression delineates the features of distinctive trophectoderm lineages and indicates that the transition from polar trophectoderm to trophoblast increases interferon-tau expression and likely drives elongation initiation. We identify 13 endometrium-derived cell types and elucidate their molecular responses to conceptus development. Integrated analyses uncover multiple paired transcripts mediating the dialogues between extraembryonic membrane and endometrium, including IGF2-IGF1R, FGF19-FGFR1, NPY-NPY1R, PROS1-AXL, and ADGRE5-CD55. These data provide insight into the molecular regulation of conceptus elongation and represent a valuable resource for functional investigations of pre- and peri-implantation ruminant development.

Atherosclerosis is a complex inflammatory disease that affects the arteries and can lead to severe complications such as heart attack and stroke. Macrophages, a type of immune cell, play a crucial role in atherosclerosis initiation and progression. Emerging studies revealed that ion channels regulate macrophage activation, polarization, phagocytosis, and cytokine secretion. Moreover, macrophage ion channel dysfunction is implicated in macrophage-derived foam cell formation and atherogenesis. In this context, exploring the regulatory role of ion channels in macrophage function and their impacts on the progression of atherosclerosis emerges as a promising avenue for research. Studies in the field will provide insights into novel therapeutic targets for the treatment of atherosclerosis.

Abstract With the skyrocketed power conversion efficiency and enhanced lifetime of perovskite solar cells (PVSCs), the environmental issues from materials to device processing, operation, and recycling become critical for their commercialization. Developing eco‐friendly PVSCs via the exploration of lead‐free perovskite materials, non‐toxic solvents, and effective lead‐adsorbing materials are the key points to realizing eco‐friendly PVSCs, which have drawn significant attention in the past 3 years. This critical review presents a comprehensive overview of the recent progress of eco‐friendly PVSCs in a close loop, including eco‐friendly perovskite materials, eco‐friendly device processing, eco‐friendly device operation, and eco‐friendly perovskite recycling. The innovation of perovskite materials, criteria of green solvent selection, and design principles of lead adsorbents are thoroughly introduced, with their combination for the device processing and operation well explained. An outlook of further material innovation and device optimization is provided to offer instruction for the development of this research field.

ObjectiveRegular check-up with ultrasound in underserved rural and/or remote areas is hampered due to the limited availability of sonologists and ultrasound devices. This study aimed to assess the feasibility and satisfaction of health check-ups with a 5G-based robotic teleultrasound diagnostic system.MethodsIn this prospective study, sonologists from two hospitals manipulated the telerobotic ultrasound system to perform teleultrasound check-ups of the liver, gallbladder, pancreas, spleen, kidneys, bladder, prostate (male), uterus and ovaries (female) for the subjects. The feasibility and satisfaction of health check-ups with a 5G-based robotic teleultrasound diagnostic system were evaluated in terms of examination results, examination duration, and satisfaction questionnaire survey.ResultsA total of 546 subjects were included with the most frequently diagnosed being abdominal disorders (n = 343) and male reproductive illnesses (n = 97), of which fatty liver (n = 204) and prostatic calcification (n = 54) were the most. The median teleultrasound examination duration (interquartile range) for men and women was 9 (9–11) min and 9 (7–11) min (p = 0.236), respectively. All the subjects were satisfied with this new type of telerobotic ultrasound check-ups and 96% reported no fear of the robotic arm during the examination.ConclusionThe 5G-based teleultrasound robotic diagnostic system in health check-ups is feasible and satisfactory, indicating that this teleultrasound robot system may have significant application value in underserved rural and/or remote areas to mitigate disparity in achieving health equity.

BackgroundIBSP is a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family that plays a vital role in bone formation, renewal and repair. Emerging evidence revealed that IBSP participated in the tumorigenesis and progression in some cancers. However, its significance in tumour prognosis and immunotherapy is still unknown.MethodsIn the current study, we studied the role of IBSP in tumorigenesis, tumor diagnosis, genomic heterogeneity, methylation modifications, immune infiltration, and therapy response in pan-cancer. In addition, we constructed a risk score model to assessed the prognostic classification efficiency of IBSP using the co-expression genes of IBSP in osteosarcoma (OS), and analyzed the expression and role of IBSP in OS through a series of assays in vitro.ResultsIBSP was upregulated in various cancers compared to the paired normal tissues, and it was strongly correlated with the prognosis, pathological stage, diagnostic accuracy, genomic heterogeneity, methylation modification, immune infiltration, immune and checkpoint. Moreover, the predictive model we established in combination with the clinical characteristics of OS patients showed high survival predictive power in these individuals. The assays in vitro showed that IBSP promoted the proliferation, migration and invasion of OS cells, which further confirmed IBSP’s role in cancers.ConclusionsOur research revealed the multifunctionality of IBSP in the tumorigenesis, progression and therapy in various cancers, which demonstrated that IBSP may serve as a potential prognostic biomarker and a novel immunotherapy target in pan-cancer.

Diabetes mellitus is an established risk factor for periodontal disease that can aggravate the severity of periodontal inflammation and accelerate periodontal destruction. The chronic high glucose condition is a hallmark of diabetes-related pathogenesis, and has been demonstrated to impair the osteogenic differentiation of periodontal ligament stem cells (PDLSCs), leading to delayed recovery of periodontal defects in diabetic patients. Reactive oxygen species (ROS) are small molecules that can influence cell fate determination and the direction of cell differentiation. Although excessive accumulation of ROS has been found to be associated with high glucose-induced cell damage, the underlying mechanisms remain unclear. Nicotinamide adenine dinucleotide phosphate (NADPH) is an important electron donor and functions as a critical ROS scavenger in antioxidant systems. It has been identified as a key mediator of various biological processes, including energy metabolism and cell differentiation. However, whether NADPH is involved in the dysregulation of ROS and further compromise of PDLSC osteogenic differentiation under high glucose conditions is still not known. In the present study, we found that PDLSCs incubated under high glucose conditions showed impaired osteogenic differentiation, excessive ROS accumulation and increased NADPH production. Furthermore, after inhibiting the synthesis of NADPH, the osteogenic differentiation of PDLSCs was significantly enhanced, accompanied by reduced cellular ROS accumulation. Our findings demonstrated the crucial role of NADPH in regulating cellular osteogenic differentiation under high glucose conditions and suggested a new target for rescuing high glucose-induced cell dysfunction and promoting tissue regeneration in the future.

Ultrasound elastography (USE) provides complementary information of tissue stiffness and elasticity to conventional ultrasound imaging. It is noninvasive and free of radiation, and has become a valuable tool to improve diagnostic performance with conventional ultrasound imaging. However, the diagnostic accuracy will be reduced due to high operator-dependence and intra- and inter-observer variability in visual observations of radiologists. Artificial intelligence (AI) has great potential to perform automatic medical image analysis tasks to provide a more objective, accurate and intelligent diagnosis. More recently, the enhanced diagnostic performance of AI applied to USE have been demonstrated for various disease evaluations. This review provides an overview of the basic concepts of USE and AI techniques for clinical radiologists and then introduces the applications of AI in USE imaging that focus on the following anatomical sites: liver, breast, thyroid and other organs for lesion detection and segmentation, machine learning (ML) - assisted classification and prognosis prediction. In addition, the existing challenges and future trends of AI in USE are also discussed.

Summary: Background: Early diagnosis of breast cancer has always been a difficult clinical challenge. We developed a deep-learning model EDL-BC to discriminate early breast cancer with ultrasound (US) benign findings. This study aimed to investigate how the EDL-BC model could help radiologists improve the detection rate of early breast cancer while reducing misdiagnosis. Methods: In this retrospective, multicentre cohort study, we developed an ensemble deep learning model called EDL-BC based on deep convolutional neural networks. The EDL-BC model was trained and internally validated on B-mode and color Doppler US image of 7955 lesions from 6795 patients between January 1, 2015 and December 31, 2021 in the First Affiliated Hospital of Army Medical University (SW), Chongqing, China. The model was assessed by internal and external validations, and outperformed radiologists. The model performance was validated in two independent external validation cohorts included 448 lesions from 391 patients between January 1 to December 31, 2021 in the Tangshan People's Hospital (TS), Chongqing, China, and 245 lesions from 235 patients between January 1 to December 31, 2021 in the Dazu People's Hospital (DZ), Chongqing, China. All lesions in the training and total validation cohort were US benign findings during screening and biopsy-confirmed malignant, benign, and benign with 3-year follow-up records. Six radiologists performed the clinical diagnostic performance of EDL-BC, and six radiologists independently reviewed the retrospective datasets on a web-based rating platform. Findings: The area under the receiver operating characteristic curve (AUC) of the internal validation cohort and two independent external validation cohorts for EDL-BC was 0.950 (95% confidence interval [CI]: 0.909–0.969), 0.956 (95% [CI]: 0.939–0.971), and 0.907 (95% [CI]: 0.877–0.938), respectively. The sensitivity values were 94.4% (95% [CI]: 72.7%–99.9%), 100% (95% [CI]: 69.2%–100%), and 80% (95% [CI]: 28.4%–99.5%), respectively, at 0.76. The AUC for accurate diagnosis of EDL-BC (0.945 [95% [CI]: 0.933–0.965]) and radiologists with artificial intelligence (AI) assistance (0.899 [95% [CI]: 0.883–0.913]) was significantly higher than that of the radiologists without AI assistance (0.716 [95% [CI]: 0.693–0.738]; p

We present the characterization of a highly segmented “large area” hybrid pixel detector (Timepix3, 512 × 512 pixels, pixel pitch 55 µm) for application in space experiments. We demonstrate that the nominal power consumption of 6 W can be reduced by changing the settings of the Timepix3 analog front-end and reducing the matrix clock frequency (from the nominal 40 MHz to 5 MHz) to 2 W (in the best case). We then present a comprehensive study of the impact of these changes on the particle tracking performance, the energy resolution and time stamping precision by utilizing data measured at the Super-Proton-Synchrotron (SPS) at CERN and at the Danish Center for Particle Therapy (DCPT). While the impact of the slower sampling frequency on energy measurement can be mitigated by prolongation of the falling edge of the analog signal, we find a reduction of the time resolution from 1.8 ns (in standard settings) to 5.6 ns (in analog low-power), which is further reduced utilizing a lower sampling clock (e.g., 5 MHz, in digital low-power operation) to 73.5 ns. We have studied the temperature dependence of the energy measurement for ambient temperatures between −20 °C and 50 °C separately for the different settings.

Age-related muscle atrophy (sarcopenia), characterized by reduced skeletal muscle mass and muscle strength, is becoming increasingly prevalent worldwide, which is especially true for older people, and can seriously damage health and quality of life in older adults. This study aims to investigate the beneficial effects of 5′-cytimidine monophosphate (CMP) on H2O2-induced muscular atrophy in C2C12 myotubes. C2C12 myotubes were treated with H2O2 in the presence and absence of CMP and the changes in the anti-oxidation, mitochondrial functions, and expression of sarcopenia-related proteins were observed. Immunofluorescence analysis showed that CMP significantly increased the diameter of myotubes. We found that CMP could increase the activity of antioxidant enzymes and improve mitochondrial dysfunction, as well as reduce inflammatory cytokine levels associated with sarcopenia. RNA-seq analysis showed that CMP could relieve insulin resistance and promote protein digestion and absorption. Western blot analysis further confirmed that CMP could promote the activation of the IRS-1/Akt/S6K signaling pathway and decrease the expression of MuRF1 and Atrogin-1, which are important markers of muscle atrophy. The above results suggest that CMP protects myotubes from H2O2-induced atrophy and that its potential mechanism is associated with activating the IRS-1/Akt/S6K pathway to promote protein synthesis by improving mitochondrial dysfunction and insulin resistance. These results indicate that CMP can improve aging-related sarcopenia.

The luminescence properties and excellent carrier transfer ability of carbon quantum dots (CQDs) have attracted much attention in the field of photocatalysis. In this work, we loaded the CQDs on the surface of Cu2O to enhance the visible-light property of Cu2O. Furthermore, the composite was used for selective oxidation of benzyl alcohol to benzaldehyde. The composite catalyst achieved high selectivity (90%) for benzaldehyde at room temperature, leveraging its visible-light-induced electron transfer properties and its photocatalytic activity for hydrogen peroxide decomposition. ·OH was shown to be the main reactive oxygen species in the selective oxidation reaction of benzyl alcohol. The formation of heterostructures of CQDs/Cu2O promoted charge carrier separation and provided a fast channel for photoinduced electron transfer. This novel material exhibited enhanced levels of activity and stability for selective oxidation of benzyl alcohol. Potential applications of carbon quantum dot composites in conventional alcohol oxidation reactions are shown.

In older men, an age-related decline in testosterone is closely associated with various adverse health outcomes. With the progression of aging, hyperactivation of the local renin–angiotensin system (RAS) and oxidative stress increase in the testis. The regulation of RAS antioxidants may be a target to delay testicular aging and maintain testosterone levels. Exogenous nucleotides (NTs) have anti-aging potential in several systems, but there are no studies of their effects on the reproductive system. In our study, we examined the effects of exogenous NTs on testosterone synthesis and explored possible mechanisms of action. Therefore, senescence-accelerated mouse prone-8 (SAMP8) mice and senescence-accelerated mouse resistant 1 (SAMR1) were used in the experiment, and they were randomly divided into an NTs free group (NTs-F), a normal control group (control), a low-dose NTs group (NTs-L), a middle-dose NTs (NTs-M), a high-dose NTs group (NTs-H) and SAMR1 groups, and the testis of the mice were collected for testing after 9 months of intervention. The results showed that exogenous NTs could increase the testicular organ index in mice during aging, and delayed the age-associated decline in testosterone levels in SAMP8 male mice, possibly by modulating the local RAS antioxidant pathway and reducing oxidative stress to protect the testis. The present study provides new research clues for the development of preventive and therapeutic strategies for related diseases.

In September 2011, Zhuonai Lake (ZL) in the northeast of Hoh Xil (HX) on the Qinghai–Tibet Plateau (QTP) broke out. The outburst event seriously changed the environmental hydraulics in this region. Due to the insufficient temporal resolution of observations, it is challenging to assess the impact of this event on short-period variations of water volumes in three lakes downstream of ZL. Combining multisource remote sensing data, we constructed long and high-temporal-resolution time series for the lake level, area, and lake water storage (LWS) of Kusai Lake (KL) to characterize the variabilities before and after the outburst. The water level, area, and LWS time series contain 1051 samples from 1990 to 2022, with uncertainties of 0.16 m, 2.5 km2, and 0.016 km3, respectively. The accuracies verified using the Database for Hydrological Time Series of Inland Waters (DAHITI) are 0.26 m, 2.64 km2, and 0.08 km3 for water level, area, and LWS, respectively. We characterized the LWS variations during the past 30 years based on the high temporal resolution LWS time series. Before the outburst, the 1-year and 3.5-year variations dominated the LWS time series, and there was no obvious semi-annual signal. After the outburst, the 3.5-year variation disappeared, and a strong semi-annual oscillation was observed. From 2012 to 2015, the periodic LWS variations in KL were disturbed by the ZL outburst and the subsequent outflow of KL led by the outburst. Regular cyclic signals have been restored since 2016, with an amplified annual fluctuation. By analysis, precipitation, evaporation, and glacier area change are excluded as driving factors of the pattern change in LWS variations of KL. It can be concluded that the altered recharge pattern of KL triggered by the outburst directly resulted in the observed changes in TWS behavior. For the first time, we identified the periodic patterns of LWS variations of KL during the past 30 years and revealed that the ZL outburst event significantly influenced these patterns. This finding contributes to the comprehensive understanding of the effects of the ZL outburst on downstream lake dynamics. Furthermore, the presented procedure for constructing long and high-resolution time series of LWS allows for monitoring and characterizing the short-period variabilities of Tibetan lakes that lack hydrological data.

Thermophilic β-1,4-endoglucanases (Cel5A) have garnered significant interest due to their potential applications in various industries, particularly in biofuel production and biorefineries. However, despite inherent stability, thermophilic Cel5A still face challenges in terms of further enhancing their catalytic efficiency and thermostability. In this study, a novel B-factor analysis method was used to predict beneficial amino acid substitutions within a 4 Å radius of the catalytic site in the tunnel of thermophilic Cel5A from Acidomyces richmondensis (ArCel5A). A combined strategy involving site-saturation mutagenesis and high-throughput screening was employed to identify the variants with the highest endoglucanase activity. Genomic sequencing revealed a mutation at position 299 in the starting strain T. reesei A2H, where the nucleotide sequence changed from TAC to TGC, resulting in a corresponding amino acid substitution from Tyrosine(Y) to Cystine(C). The endoglucanase activity of the mutant ArCel5A reached 3251 IU/mL, representing an 85.2% increase compared to wild-type ArCel5A at the fermentation time of 94 h. Significantly, the ArCel5A-Y299C mutant showed superior thermostability, retaining 93.8% of its initial activity after 30 min at 70 °C, and 91.5% after 10 min at 80 °C. Various computational simulation methods confirmed that the Y299C mutation enhanced the stability of the catalytic pocket, thereby improving the overall stability and catalytic efficiency of ArCel5A. This study offers an effective strategy for mining target sites for rational mutagenesis based on highly conserved sequences, which simultaneously improves both the thermostability and catalytic efficiency of thermophilic Cel5A.

Coal mining has caused significant soil nitrogen loss in mining areas, limiting reclamation and reuse in agriculture. This article studies the effects of organic fertilizer, inorganic fertilizer, and the combined application of Pseudomonas fluorescens with the ability of nitrogen fixation on soil nitrogen accumulation and composition in the reclamation area of the Tunlan Coal Mine from 2016 to 2022 under the conditions of equal nitrogen application, providing a scientific basis for microbial fertilization and the rapid increase in nitrogen content in the reclaimed soil of mining areas. The results showed that as the reclamation time increased, the nitrogen content and the composition and structure of the soil treated with fertilization rapidly evolved toward normal farmland soil. The soil nitrogen content increased most rapidly in the presence of added P. fluorescens + organic fertilizer (MB). Compared to other treatments (inorganic fertilizer (CF), organic fertilizer (M), and P. fluorescens + inorganic fertilizer (CFB)), MB increased total nitrogen (TN) to normal farmland soil levels 1–3 years earlier. The comprehensive scores of MB and CFB on the two principal components increased by 1.58 and 0.79 compared to those of M and CF treatments, respectively. This indicates that the combination of P. fluorescens and organic fertilizer improves soil nitrogen accumulation more effectively than the combination of P. fluorescens and inorganic fertilizer. In addition, the application of P. fluorescens increases the content of unknown nitrogen (UN) in acid-hydrolysable nitrogen (AHN) and decreases the content of amino acid nitrogen (AAN) and ammonia nitrogen (AN). However, there was no significant effect on the content of ammonium nitrogen (NH4+-N) and nitrate nitrogen (NO3−-N) in soil-mineralized nitrogen (SMN). When combined with inorganic fertilizer, the contribution of SMN to TN increased by 14.78%, while when combined with organic fertilizer, the contribution of AHN to TN increased by 44.77%. In summary, the use of P. fluorescens is beneficial for nitrogen recovery in the reclaimed soil of coal-mining areas. The optimal fertilization method under the experimental conditions is the combination of P. fluorescens and organic fertilizer.

The role of lncRNA Gm20743 in the development of diabetic sarcopenia is explored using a mouse model.

Abstract Exploring the functions of human-specific genes (HSGs) is challenging due to the lack of a tractable genetic model system. Testosterone is essential for maintaining human spermatogenesis and fertility, but the underlying mechanism is unclear. Here, we identified Cancer/Testis Antigen gene family 47 (CT47) as an essential regulator of human-specific spermatogenesis by stabilizing arginine methyltransferase 5 (PRMT5). A humanized mouse model revealed that CT47 functions to arrest spermatogenesis by interacting with and regulating CT47/PRMT5 accumulation in the nucleus during the leptotene/zygotene-to-pachytene transition of meiosis. We demonstrate that testosterone induces nuclear depletion of CT47/PRMT5 and rescues leptotene-arrested spermatocyte progression in humanized testes. Loss of CT47 in human embryonic stem cells (hESCs) by CRISPR/Cas9 led to an increase in haploid cells but blocked the testosterone-induced increase in haploid cells when hESCs were differentiated into haploid spermatogenic cells. Moreover, CT47 levels were decreased in nonobstructive azoospermia. Together, these results established CT47 as a crucial regulator of human spermatogenesis by preventing meiosis initiation before the testosterone surge.

Quantification of anion binding by molecular receptors within lipid bilayers is challenging. Here, the authors synthesise a high-affinity macrocyclic anion receptor which provides insights into determinants of anion binding within lipid bilayers.