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Abstract Premature infants are often exposed to hyperoxia. However, there is limited data regarding the mechanistic underpinnings linking neonatal hyperoxia exposure and its contribution to cardio-renal dysfunction in adults born preterm. Our objective was to determine whether neonatal hyperoxia induces systemic vascular stiffness and cardio-renal dysfunction in adulthood. Newborn rats were randomly assigned to room air (RA) or hyperoxia (85% O2) from postnatal day 1 to 14, then recovered in RA until 1 year of life. Arterial stiffness, cardio-renal histomorphometry, and fibrosis in the aorta, heart, and kidney were assessed. RNA-sequencing (RNA-seq) of the aorta and kidney was also done. Adult rats exposed to neonatal hyperoxia had increased aortic and mesenteric artery stiffness as demonstrated by wire and pressure myography. They also had cardiomyocyte hypertrophy, glomerulomegaly, and tubular injury. Hyperoxia exposure altered the transcriptome profile associated with fibrosis and matrix remodeling in the aorta and kidney. There was also increased TGF-β1 levels and fibrosis in the aorta, left ventricle, and kidney. In conclusion, neonatal hyperoxia exposure was associated with systemic vascular and cardio-renal alterations in 1-year-old rats. Further studies to determine how targeted therapies could reprogram cardio-renal injury after neonatal hyperoxia exposure are indicated.

Abstract Introduction Premature ovarian insufficiency (POI) is one of the causes of female infertility. Unexplained POI is increasingly affecting women in their reproductive years. However, the etiology of POI is diverse and remains elusive. We and others have shown that brain-derived neurotrophic factor (BDNF) plays an important role in adult ovarian function. Here, we report on a novel role of BDNF in the Developmental Origins of POI. Methods Placental BDNF knockout mice were created using CRISPR/CAS9. Homozygous knockout (cKO(HO)) mice didn’t survive, while heterozygous knockout (cKO(HE)) mice did. BDNF reduction in cKO(HE) mice was confirmed via immunohistochemistry and Western blots. Ovaries were collected from cKO(HE) mice at various ages, analyzing ovarian metrics, FSH expression, and litter sizes. In one-month-old mice, oocyte numbers were assessed using super-ovulation, and oocyte gene expression was analyzed with smart RNAseq. Ovaries of P7 mice were studied with SEM, and gene expression was confirmed with RT-qPCR. Alkaline phosphatase staining at E11.5 and immunofluorescence for cyclinD1 assessed germ cell number and cell proliferation. Results cKO(HE) mice had decreased ovarian function and litter size in adulthood. They were insensitive to ovulation induction drugs manifested by lower oocyte release after superovulation in one-month-old cKO(HE) mice. The transcriptome and SEM results indicate that mitochondria-mediated cell death or aging might occur in cKO(HE) ovaries. Decreased placental BDNF led to diminished primordial germ cell proliferation at E11.5 and ovarian reserve which may underlie POI in adulthood. Conclusion The current results showed decreased placental BDNF diminished primordial germ cell proliferation in female fetuses during pregnancy and POI in adulthood. Our findings can provide insights into understanding the underlying mechanisms of POI.

Abstract It is important to ensure the nutritional quality and safe production of rice. Here, plot experiments were used to analyze the effects of three soil amendments—10 t ha−1 of biochar (BC), 1.5 t ha−1 of lime (LM), and 2.25 t ha−1 of silicon–calcium fertilizer (SC)—on the soil characteristics, rice yield and quality of double-cropping rice grown in mildly cadmium-polluted paddy fields. Compared with the control treatment (CK), the BC and SC treatments significantly improved rice processing, appearance and nutritional quality, but reduced cooking quality. All three soil amendments significantly reduced cadmium (Cd) content in brown rice. Soil amendments could significantly increase soil pH and reduce soil available Cd content. The application of the BC and SC treatments increased the content of each nutrient index in the soil (SOM, NN, AP, AK). Correlation analysis showed that the improvement in rice processing, appearance, and nutritional quality was mainly affected by the comprehensive effects of soil SOM, NN, AP and AK; the hygiene quality was mainly affected by soil pH and available Cd. In terms of benefit analysis combined with cost, the SC treatment had the highest benefit effect. Taken together, in mildly cadmium-polluted paddy fields, the application of silicon–calcium fertilizer improved the soil quality, thereby increased the yield and quality of rice, and had the best effect on increasing income.

Artificial Intelligence (AI) and robotic technologies have been applied in healthcare sectors for many years. Along with the ageing trend rising globally, the use of AI and intelligent service robots in home care for elderly or disabled bedridden people has generated considerable attention. A robot that can physically assist care-workers and the elderly or disabled bedridden people in daily activities may help ease care-workers’ burden and help older people live independently for longer with higher quality of life. This survey gives a comprehensive overview in the latest AI and robotic technologies applications in elderly care, providing a detailed analysis on the current products in the market, and discusses the problems and the future trend in this topic.

Abstract Background Soil salinization is one of the vital factors threatening the world’s food security. To reveal the biological mechanism of response to salt stress in wheat, this study was conducted to resolve the transcription level difference to salt stress between CM6005 (salt-tolerant) and KN9204 (salt-sensitive) at the germination and seedling stage. Results To investigate the molecular mechanism underlying salt tolerance in wheat, we conducted comprehensive transcriptome analyses at the seedling and germination stages. Two wheat cultivars, CM6005 (salt-tolerant) and KN9204 (salt-sensitive) were subjected to salt treatment, resulting in a total of 24 transcriptomes. Through expression-network analysis, we identified 17 modules, 16 and 13 of which highly correlate with salt tolerance-related phenotypes in the germination and seedling stages, respectively. Moreover, we identified candidate Hub genes associated with specific modules and explored their regulatory relationships using co-expression data. Enrichment analysis revealed specific enrichment of gibberellin-related terms and pathways in CM6005, highlighting the potential importance of gibberellin regulation in enhancing salt tolerance. In contrast, KN9204 exhibited specific enrichment in glutathione-related terms and activities, suggesting the involvement of glutathione-mediated antioxidant mechanisms in conferring resistance to salt stress. Additionally, glucose transport was found to be a fundamental mechanism for salt tolerance during wheat seedling and germination stages, indicating its potential universality in wheat. Wheat plants improve their resilience and productivity by utilizing adaptive mechanisms like adjusting osmotic balance, bolstering antioxidant defenses, accumulating compatible solutes, altering root morphology, and regulating hormones, enabling them to better withstand extended periods of salt stress. Conclusion Through utilizing transcriptome-level analysis employing WGCNA, we have revealed a potential regulatory mechanism that governs the response to salt stress and recovery in wheat cultivars. Furthermore, we have identified key candidate central genes that play a crucial role in this mechanism. These central genes are likely to be vital components within the gene expression network associated with salt tolerance. The findings of this study strongly support the molecular breeding of salt-tolerant wheat, particularly by utilizing the genetic advancements based on CM6005 and KN9204.

BackgroundOxidative stress and apoptosis of neurons significantly contribute to the pathophysiological cascade of spinal cord injury (SCI). However, the role of hypoxic-preconditioned mesenchymal stem cell-derived small extracellular vesicles (H-sEVs) in promoting SCI repair remains unclear. Hence, the present study aims to investigate the regulatory effects of H-sEVs on neuronal oxidative stress and apoptotic responses following SCI.MethodsThe administration of H-sEVs of SCI rats was assessed using behavioral evaluations such as Basso-Beattie-Bresnahan (BBB) scores, neuroelectrophysiological monitoring, and Catwalk gait analysis. Indices of oxidative stress (including superoxide dismutase [SOD], total antioxidant capacity [T-AOC], and malondialdehyde [MDA]) were measured. Neuronal survival was evaluated through Nissl staining, while the expression level of sirtuin 1 (SIRT1) was examined using immunohistochemical staining. Additionally, histological evaluation of lesion size was performed using hematoxylin-eosin (HE) staining. Tunel cell apoptosis staining and analysis of apoptosis-associated proteins (B-cell lymphoma-2 [Bcl2] and BCL2-Associated X [Bax]) were conducted through immunofluorescence staining and western blot, respectively. Furthermore, the model of oxidative stress was established using PC12 cells, and apoptosis levels were assessed via flow cytometry and western blot analysis. Importantly, to ascertain the critical role of SIRT1, we performed SIRT1 knockout experiments in PC12 cells using lentivirus transfection, followed by western blot.ResultsUsing those behavioral evaluations, we observed significant functional improvement after H-sEVs treatment. Nissl staining revealed that H-sEVs treatment promoted neuronal survival. Moreover, we found that H-sEVs effectively reduced oxidative stress levels after SCI. HE staining demonstrated that H-sEVs could reduce lesion area. Immunohistochemical analysis revealed that H-sEVs enhanced SIRT1 expression. Furthermore, Tunel cell apoptosis staining and western blot analysis of apoptosis-related proteins confirmed the anti-apoptotic effects of H-sEVs. The PC12 cells were used to further substantiate the neuroprotective properties of H-sEVs by significantly inhibiting neuronal death and attenuating oxidative stress. Remarkably, SIRT1 knockout in PC12 cells reversed the antioxidant stress effects induced by H-sEVs treatment. Additionally, we elucidated the involvement of the downstream Nrf2/HO-1 signaling pathway.ConclusionOur study provides valuable insights into the effects of H-sEVs on neuronal oxidative stress and apoptosis after SCI. These findings underscore the potential clinical significance of H-sEVs-based therapies for SCI.

BackgroundOvarian carcinoma (OC) is a prevalent gynecological malignancy associated with high recurrence rates and mortality, often diagnosed at advanced stages. Despite advances in immunotherapy, immune exhaustion remains a significant challenge in achieving optimal tumor control. However, the exploration of intratumoral heterogeneity of malignant epithelial cells and the ovarian cancer tumor microenvironment is still limited, hindering our comprehensive understanding of the disease.Materials and methodsUtilizing single-cell RNA sequencing (scRNA-seq), we comprehensively investigated the cellular composition across six ovarian cancer patients with omental metastasis. Our focus centered on analysis of the malignant epithelial cells. Employing CytoTRACE and slingshot pseudotime analyses, we identified critical subpopulations and explored associated transcription factors (TFs) influencing ovarian cancer progression. Furthermore, by integrating clinical factors from a large cohort of bulk RNA sequencing data, we have established a novel prognostic model to investigate the impact of the tumor immune microenvironment on ovarian cancer patients. Furthermore, we have investigated the condition of immunological exhaustion.ResultsOur study identified a distinct and highly proliferative subgroup of malignant epithelial cells, known as C2 TOP2A+ TCs. This subgroup primarily consisted of patients who hadn’t received neoadjuvant chemotherapy. Ovarian cancer patients with elevated TOP2A expression exhibited heightened sensitivity to neoadjuvant chemotherapy (NACT). Moreover, the transcription factor MYBL2 in this subgroup played a critical role in ovarian cancer development. Additionally, we developed an independent prognostic indicator, the TOP2A TCs Risk Score (TTRS), which revealed a correlation between the High TTRS Group and unfavorable outcomes. Furthermore, immune infiltration and drug sensitivity analyses demonstrated increased responsiveness to Paclitaxel, Cisplatin, and Gemcitabine in the Low TTRS Group.ConclusionThis research deepens our understanding of malignant epithelial cells in ovarian cancer and enhances our knowledge of the ovarian cancer immune microenvironment and immune exhaustion. We have revealed the heightened susceptibility of the C2 TOP2A+ TCs subgroup to neoadjuvant chemotherapy and emphasized the role of MYBL2 within the C2 subgroup in promoting the occurrence and progression of ovarian cancer. These insights provide valuable guidance for the management of ovarian cancer treatment.

Preclinical evidence has firmly established a bidirectional interaction among the lung, gut, and gut microbiome. There are many complex communication pathways between the lung and intestine, which affect each other's balance. Some metabolites produced by intestinal microorganisms, intestinal immune cells, and immune factors enter lung tissue through blood circulation and participate in lung immune function. Altered gut–lung–microbiome interactions have been identified in rodent models and humans of several lung diseases such as pulmonary fibrosis, chronic obstructive pulmonary disease, lung cancer, asthma, etc. Emerging evidence suggests that microbial therapies can prevent and treat respiratory diseases, but it is unclear whether this association is a simple correlation with the pathological mechanisms of the disease or the result of causation. In this review, we summarize the complex and critical link between the gut microbiota and the lung, as well as the influence and mechanism of the gut microbiota on respiratory diseases, and discuss the role of interventions such as prebiotics and fecal bacteria transplantation on respiratory diseases. To provide a reference for the rational design of large-scale clinical studies, the direct application of microbial therapy to respiratory-related diseases can reduce the incidence and severity of diseases and accompanying complications.

Abstract Cuproptosis and disulfidptosis, recently discovered mechanisms of cell death, have demonstrated that differential expression of key genes and long non-coding RNAs (lncRNAs) profoundly influences tumor development and affects their drug sensitivity. Clear cell renal cell carcinoma (ccRCC), the most common subtype of kidney cancer, presently lacks research utilizing cuproptosis and disulfidptosis-related lncRNAs (CDRLRs) as prognostic markers. In this study, we analyzed RNA-seq data, clinical information, and mutation data from The Cancer Genome Atlas (TCGA) on ccRCC and cross-referenced it with known cuproptosis and disulfidptosis-related genes (CDRGs). Using the LASSO machine learning algorithm, we identified four CDRLRs—ACVR2B-AS1, AC095055.1, AL161782.1, and MANEA-DT—that are strongly associated with prognosis and used them to construct a prognostic risk model. To verify the model's reliability and validate these four CDRLRs as significant prognostic factors, we performed dataset grouping validation, followed by RT-qPCR and external database validation for differential expression and prognosis of CDRLRs in ccRCC. Gene function and pathway analysis were conducted using Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA) for high- and low-risk groups. Additionally, we have analyzed the tumor mutation burden (TMB) and the immune microenvironment (TME), employing the oncoPredict and Immunophenoscore (IPS) algorithms to assess the sensitivity of diverse risk categories to targeted therapeutics and immunosuppressants. Our predominant objective is to refine prognostic predictions for patients with ccRCC and inform treatment decisions by conducting an exhaustive study on cuproptosis and disulfidptosis.

The transient receptor potential melastatin 7 channel (TRPM7) is a nonselective cation channel highly expressed in some human cancer tissues. TRPM7 is involved in the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of cancer cells. Modulation of TRPM7 could be a promising therapeutic strategy for treating cancer; however, efficient and selective pharmacological TRPM7 modulators are lacking. In this study we investigated N- [4- (4, 6-dimethyl- 2-pyrimidinyloxy) − 3- methylphenyl] -N’ - [2 -(dimethylamino)] benzoylurea (SUD), a newly synthesized benzoylurea derivative, for its effects on cancer cell migration and EMT and on functional expression of TRPM7. Our previous studies showed that SUD induces cell cycle arrest and apoptosis of MCF-7 and BGC-823 cells (human breast cancer and gastric cancer cell lines, respectively). Here, we show that SUD significantly decreased the migration of both types of cancer cells. Moreover, SUD decreased vimentin expression and increased E-cadherin expression in both cell types, indicating that EMT is also decreased by SUD. Importantly, SUD potentially reduced the TRPM7-like current in a concentration-dependent manner and decreased TRPM7 expression through the PI3K/Akt signaling pathway. Finally, molecular docking simulations were used to investigate potential SUD binding sites on TRPM7. In summary, our research demonstrated that SUD is an effective TRPM7 inhibitor and a potential agent to suppress the metastasis of breast and gastric cancer by inhibiting TRPM7 expression and function.

The occurrence of excitotoxic damage caused by cerebral ischemia-reperfusion (I/R) injury is closely linked to a decrease in central inhibitory function, in which the concentration of chloride inside the cells ([Cl−]i) plays a crucial role. The outflow and inflow of [Cl−]i are controlled by KCC2 and NKCC1, which are cellular cotransporters for K+/Cl− and Na+/K+/Cl−, respectively. NKCC1/KCC2 is regulated by upstream regulators such as SPAK and OSR1, whose activity is influenced by I/R. Sevoflurane is the most commonly used and controversial general anesthetic. To elucidate the impact of sevoflurane on cerebral ischemia-reperfusion (I/R) injury and its underlying mechanism, we investigated its influence on cognitive function and the mechanism of action utilizing a rat model of I/R. By activating the kinase Spak/OSR1, we discovered that I/R damage enhanced the function of NKCC1 and inhibited the function of KCC2, which triggered an imbalance of [Cl−]i concentration, leading to neurological dysfunction and cognitive dysfunction. At the beginning of reperfusion, administration of 1.3 MAC sevoflurane for 3 h increased activation of Spak/OSR1 kinases on day 7 post-perfusion, resulting in an additional dysregulation of NKCC1 and KCC2 activity, which disappeared on day 14. Administration of Closantel, a Spak/OSR1 kinase inhibitor, to animals treated with sevoflurane reverses the additional stimulation. The research revealed that sevoflurane modified the functioning of NKCC1 and KCC2, resulting in cognitive decline by activating Spak/OSR1 kinase. However, this issue could be resolved by inhibiting Spak/OSR1. The research revealed that sevoflurane transiently alters the function of NKCC1 and KCC2, resulting in exacerbating cognitive decline. However, this can be fixed by suppressing Spak/OSR1.

BackgroundThere was little evidence of autologous stem cell transplantation (ASCT) as consolidation therapy after remission of induction for patients with Peripheral T-cell lymphoma (PTCL). In this study, we conducted a comparative analysis of real-world survival outcomes between consolidation therapy and observation in patients with PTCL.MethodsA total of 92 patients with peripheral T-cell lymphoma (PTCL) who were admitted to the Department of Hematology, Huadong Hospital Affiliated with Fudan University from January 2013 to April 2019 were divided into two groups based on whether they were treated with high-dose therapy (HDT) followed by autologous hematopoietic stem cell transplantation (ASCT): ASCT as consolidation therapy (n=30) and observation (n=62). Clinical characteristics, treatment patterns, and survival outcomes were analyzed between the two groups. Univariate and Cox multivariate regression analyses were also performed to detect prognostic factors of survival.ResultsWith a median follow-up time of 41 months, the median overall survival (OS) of peripheral T-cell lymphoma patients treated with ASCT was not reached; the median progression-free survival (PFS) was 77.0 months, which was much higher than that of patients without ASCT (p

IntroductionThe ratoon rice planting area is gradually expanding, but there has been relatively little research on ratoon rice grains contaminated with Cd.MethodsIn this study, five ratoon rice varieties were selected and divided into three groups according to early-maturity (growth duration: 100–110 days), mid-maturity (growth duration: 110–120 days) and late-maturity (growth duration: 120–130 days) varieties. Field experiments were done to study the differences in Cd accumulation among ratoon rice varieties with different growth duration.ResultsThe results showed that the Cd accumulation and concentration of grains spikelet at each growth stage in the main crop were in the order of late-maturity > mid-maturity > early-maturity varieties. However, the trends in Cd concentration and accumulation in grains spikelet during the ratoon crop were the opposite. Analysis found that as the growth duration of the variety extended, the accumulated temperature and daily average temperature in the main crop increased, which significantly increased the translocation factors of Cd from root, stem, and leaf to grains spikelet, and increased the daily average Cd accumulation rate in grains spikelet. The daily average temperature in the ratoon crop increased as the growth duration shortened. The early-maturity variety had higher Cd accumulation in stubble, which promoted the translocation of Cd from the root, stem, and leaf of the plant to the grains spikelet.DiscussionTherefore, appropriately shortening the growth duration of the main crop and extending the growth duration of the ratoon crop are important ways to reduce Cd accumulation in ratoon rice in areas with mild Cd pollution.

Friction rolling additive manufacturing (FRAM) is a solid-state additive manufacturing method capable of accommodating a wide range of material forms. However, there is a lack of comprehensive research on the optimal feedstock form. Thus, this study investigated the influence of feedstock shape on material formation, microstructure, and mechanical properties. The results revealed that irrespective of whether a strip or wire was used, the plasticized material flowed through a thin plastic flow channel (approximately 112 μm) between the tool head and the feedstock. Wire feedstock resulted in greater deformation and more significant grain refinement than strip feedstock, with grain refinements of 95 % and 81 %, respectively. Additionally, gaps between multiple wires were filled with plasticized material, forming a dense and defect-free mixing zone. Moreover, the tensile performances of the deposited samples obtained from wire and strip feedstocks exhibited no significant differences, measuring 143.9 MPa and 144.5 MPa, respectively. Numerical simulations were employed to elucidate the underlying mechanism of the temperature field and material flow behavior when strips and wires were used as feed materials. The findings of this study are anticipated to serve as a reference for selecting feedstock forms for FRAM.

Abstract The upper lip bite test (ULBT) is considered an effective method for predicting difficult airways, but data on the ULBT for predicting difficult tracheal intubation are lacking. This study aimed to examine the clinical utility of the ULBT in predicting difficult endotracheal intubation. We conducted an observational case-cohort study of adult patients undergoing elective surgery and requiring endotracheal intubation for general anesthesia. Difficult airway assessment was performed on the recruited patients before the operation, including the ULBT, mouth opening, thyromental distance, modified Mallampati test, and body mass index. The primary outcome was the incidence of difficult tracheal intubation. The receiver operating characteristic curve analysis was used to compare the performance of variables in predicting difficult tracheal intubation. We successfully recruited 2522 patients for analysis and observed 64 patients with difficult tracheal intubation. When predicting difficult tracheal intubation, grade 2 ULBT had a sensitivity of 0.75 and a specificity of 0.54, and grade 3 had a sensitivity of 0.28 and a specificity of 0.75. Compared with mouth opening, the area under the receiver operating characteristic curve of the ULBT was lower in predicting difficult tracheal intubation (0.69 [95% confidence interval: 0.67–0.71] vs. 0.84 [95% confidence interval: 0.82–0.87], P

Abstract Neonatal hyperoxia induces long-term systemic vascular stiffness and cardiovascular remodeling, but the mechanisms are unclear. Chemokine receptor 7 (CXCR7) represents a key regulator of vascular homeostasis and repair by modulating TGF-β1 signaling. This study investigated whether pharmacological CXCR7 agonism prevents neonatal hyperoxia-induced systemic vascular stiffness and cardiac dysfunction in juvenile rats. Newborn Sprague Dawley rat pups assigned to room air or hyperoxia (85% oxygen), received CXCR7 agonist, TC14012 or placebo for 3 weeks. These rat pups were maintained in room air until 6 weeks when aortic pulse wave velocity doppler, cardiac echocardiography, aortic and left ventricular (LV) fibrosis were assessed. Neonatal hyperoxia induced systemic vascular stiffness and cardiac dysfunction in 6-week-old rats. This was associated with decreased aortic and LV CXCR7 expression. Early treatment with TC14012, partially protected against neonatal hyperoxia-induced systemic vascular stiffness and improved LV dysfunction and fibrosis in juvenile rats by decreasing TGF-β1 expression. In vitro, hyperoxia-exposed human umbilical arterial endothelial cells and coronary artery endothelial cells had increased TGF-β1 levels. However, treatment with TC14012 significantly reduced the TGF-β1 levels. These results suggest that dysregulation of endothelial CXCR7 signaling may contribute to neonatal hyperoxia-induced systemic vascular stiffness and cardiac dysfunction.

Abstract Background The anatomical characteristics of difficult airways can be analysed geometrically. This study aims to develop and validate a geometry-assisted difficult airway screening method (GADAS method) for difficult tracheal intubation. Methods In the GADAS method, a geometric simulated model was established based on computer graphics. According to the law of deformation of the upper airway on laryngoscopy, the expected visibility of the glottis was calculated to simulate the real visibility on laryngoscopy. Validation of the new method: Approved by the Ethics Committee of Yijishan Hospital of Wannan Medical College. Adult patients who needed tracheal intubation under general anaesthesia for elective surgery were enrolled. The data of patients were input into the computer software to calculate the expected visibility of the glottis. The results of tracheal intubation were recorded by anaesthesiologists. The primary observation outcome was the screening performance of the expected visibility of the glottis for difficult tracheal intubation. Results The geometric model and software of the GADAS method were successfully developed and are available for use. We successfully observed 2068 patients, of whom 56 patients had difficult intubation. The area under the receiver operating characteristic curve of low expected glottis visibility for predicting difficult laryngoscopy was 0.96 (95% confidence interval [CI]: 0.95–0.96). The sensitivity and specificity were 89.3% (95% CI: 78.1-96.0%) and 94.3% (95% CI: 93.2%-95.3), respectively. Conclusions It is feasible to screen difficult-airway patients by applying computer techniques to simulate geometric changes in the upper airway.

Abstract Epidermal growth factor receptor‐targeted (EGFR‐targeted) therapies show promise for non‐small cell lung cancer (NSCLC), but they are ineffective in a third of patients who lack EGFR mutations. This underlines the need for personalized treatments for patients with EGFR wild‐type NSCLC. A genome‐wide CRISPR/Cas9 screen has identified the enzyme phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS), which is vital in de novo purine biosynthesis and tumor development, as a potential drug target for EGFR wild‐type NSCLC. We have further confirmed that PAICS expression is significantly increased in NSCLC tissues and correlates with poor patient prognosis. Knockdown of PAICS resulted in a marked reduction in both in vitro and in vivo proliferation of EGFR wild‐type NSCLC cells. Additionally, PAICS silencing led to cell‐cycle arrest in these cells, with genes involved in the cell cycle pathway being differentially expressed. Consistently, an increase in cell proliferation ability and colony number was observed in cells with upregulated PAICS in EGFR wild‐type NSCLC. PAICS silencing also caused DNA damage and cell‐cycle arrest by interacting with DNA repair genes. Moreover, decreased IMPDH2 activity and activated PI3K–AKT signaling were observed in NSCLC cells with EGFR mutations, which may compromise the effectiveness of PAICS knockdown. Therefore, PAICS plays an oncogenic role in EGFR wild‐type NSCLC and represents a potential therapeutic target for this disease.

Background: Intra-amniotic inflammation (IAI) is associated with increased risk of preterm birth and bronchopulmonary dysplasia (BPD), but the mechanisms by which IAI leads to preterm birth and BPD are poorly understood, and there are no effective therapies for preterm birth and BPD. The transcription factor c-Myc regulates various biological processes like cell growth, apoptosis, and inflammation. We hypothesized that c-Myc modulates inflammation at the maternal-fetal interface, and neonatal lung remodeling. The objectives of our study were 1) to determine the kinetics of c-Myc in the placenta, fetal membranes and neonatal lungs exposed to IAI, and 2) to determine the role of c-Myc in modulating inflammation at the maternal-fetal interface, and neonatal lung remodeling induced by IAI.Methods: Pregnant Sprague-Dawley rats were randomized into three groups: 1) Intra-amniotic saline injections only (control), 2) Intra-amniotic lipopolysaccharide (LPS) injections only, and 3) Intra-amniotic LPS injections with c-Myc inhibitor 10058-F4. c-Myc expression, markers of inflammation, angiogenesis, immunohistochemistry, and transcriptomic analyses were performed on placenta and fetal membranes, and neonatal lungs to determine kinetics of c-Myc expression in response to IAI, and effects of prenatal systemic c-Myc inhibition on lung remodeling at postnatal day 14.Results: c-Myc was upregulated in the placenta, fetal membranes, and neonatal lungs exposed to IAI. IAI caused neutrophil infiltration and neutrophil extracellular trap (NET) formation in the placenta and fetal membranes, and neonatal lung remodeling with pulmonary hypertension consistent with a BPD phenotype. Prenatal inhibition of c-Myc with 10058-F4 in IAI decreased neutrophil infiltration and NET formation, and improved neonatal lung remodeling induced by LPS, with improved alveolarization, increased angiogenesis, and decreased pulmonary vascular remodeling.Discussion: In a rat model of IAI, c-Myc regulates neutrophil recruitment and NET formation in the placenta and fetal membranes. c-Myc also participates in neonatal lung remodeling induced by IAI. Further studies are needed to investigate c-Myc as a potential therapeutic target for IAI and IAI-associated BPD.

Abstract There have been contradictory reports on the biological role of transforming growth factor‐βs (TGFβs) in breast cancer (BC), especially with regard to their ability to promote epithelial‐mesenchymal transition (EMT). Here, we show that TGFβ2 is preferentially expressed in mesenchymal‐like BCs and maintains the EMT phenotype, correlating with cancer stem cell‐like characteristics, growth, metastasis and chemo‐resistance and predicting worse clinical outcomes. However, this is only true in ERα− BC. In ERα+ luminal‐type BC, estrogen receptor interacts with p‐Smads to block TGFβ signalling. Furthermore, we also identify a microRNAs (miRNAs) signature (miRNAsTGFβ2) that is weakened in TGFβ2‐overexpressing BC cells. We discover that TGFβ2‐Snail1 recruits enhancer of zeste homolog‐2 to convert miRNAsTGFβ2 promoters from an active to repressive chromatin configuration and then repress miRNAsTGFβ2 transcription, forming a negative feedback loop. On the other hand, miRNAsTGFβ2 overexpression reverses the mesenchymal‐like traits in agreement with the inhibition of TGFβ2‐Snail1 signalling in BC cells. These findings clarify the roles of TGFβ2 in BC and suggest novel therapeutic strategies based on the TGFβ2‐Snail1‐miRNAsTGFβ2 loop for a subset type of human BCs.

Introduction: Idiopathic pulmonary fibrosis is a chronic interstitial lung disease characterized by excessive deposition of extracellular matrix. Cannabidiol, a natural component extracted from plant cannabis, has been shown to have therapeutic effects on lung diseases, but its exact mechanism of action is unknown, hindering its therapeutic effectiveness.Methods: To establish a pulmonary fibrosis model, combined with UPLC-Q-TOF/MS metabolomics and 16S rDNA sequencing, to explore cannabidiol’s mechanism in treating pulmonary fibrosis. The rats were randomly divided into the control group, pulmonary fibrosis model group, prednisone treatment group, and cannabidiol low, medium, and high dose groups. The expression levels of HYP, SOD, and MDA in lung tissue and the expression levels of TNF-α, IL-1β, and IL-6 in serum were detected. Intestinal microbiota was detected using UPLC-QTOF/MS analysis of metabolomic properties and 16S rDNA sequencing.Results: Pathological studies and biochemical indexes showed that cannabidiol treatment could significantly alleviate IPF symptoms, significantly reduce the levels of TNF-α, IL-1β, IL-6, MDA, and HYP, and increase the expression level of SOD (p < 0.05). CBD-H can regulate Lachnospiraceae_NK4A136_group, Pseudomonas, Clostridia_UCG-014, Collinsella, Prevotella, [Eubacterium]_coprostanoligenes_group, Fusobacterium, Ruminococcus, and Streptococcus, it can restore intestinal microbiota function and reverse fecal metabolism trend. It also plays the role of fibrosis through the metabolism of linoleic acid, glycerol, linolenic acid, and sphingolipid.Discussion: Cannabidiol reverses intestinal microbiota imbalance and attenuates pulmonary fibrosis in rats through anti-inflammatory, antioxidant, and anti-fibrotic effects. This study lays the foundation for future research on the pathological mechanisms of IPF and the development of new drug candidates.

Abstract Recently, segmentation-based approaches have been proposed to tackle arbitrary-shaped text detection. The trade-off between speed and accuracy is still a challenge that hinders its deployment in practical applications. Previous methods adopt complex pipelines to improve accuracy while ignoring inference speed. Moreover, the performance of most efficient scene text detectors often suffers from weak feature extraction when equipping lightweight networks. In this paper, we propose a novel distillation method for efficient and accurate arbitrary-shaped text detection, termed kernel-mask knowledge distillation. Our approach equips a low computational-cost visual transformer module (VTM) and a feature adaptation layer to make full use of feature-based and response-based knowledge in distillation. More specifically, first, the text features are obtained by aggregating the multi-level information extracted in the respective backbones of the teacher and student networks. Second, the text features are respectively sent to the VTM to enhance the feature representation ability. Then, we distill the feature-based and response-based kernel knowledge of the teacher network to obtain an efficient and accurate arbitrary-shaped text detection model. Extensive experiments on publicly available datasets demonstrate the state-of-the-art performance of our method. It is worth noting that our method can achieve a competitive F-measure of 86.92% at 34.5 FPS on Total-text. Code is available at https://github.com/giganticpower/KKDnet .

Abstract Hypertension is the most prevalent chronic disease World-wide, and the leading preventable risk factor for cardiovascular disease (CVD). Few patients accomplish the objective of decreasing blood pressure and avoiding hypertensive target organ damage after treatments with antihypertensive agents which opens the door for other treatments, such as herbal-and antihypertensive combination therapy. Captopril (CAP), as a-pril which inhibits angiotensin converting enzyme has long been used in the management of hypertension and CVD. Gedan Jiangya Decoction (GJD) is known for antihypertensive effects in prior studies. The research is aimed to determine whether GJD in combination with captopril has antihypertensive, kidney protective, antioxidant, and vasoactive effects in spontaneously hypertensive rats (SHR). Regular measurements of systolic and diastolic blood pressure (SBP and DBP), and body weight were monitored weekly. H&E staining was utilized to examine histopathology. The combined effects were studied using ELISA, immunohistochemistry, and qRT-PCR. Significant reductions in SBP, DBP, aortic wall thickness, and improvement in renal tissue were observed following GJD + CAP treatment, with increased serum levels of NO, SOD, GSH-Px, and CAT and decreases in Ang II, ET-1, and MDA. Similarly, GJD + CAP treatment of SHR's significantly decreased ET-1 and AGTR1 mRNA and protein expression while increasing eNOS mRNA and protein expression in thoracic aorta and kidney tissue. In conclusion, the present investigation found that GJD + CAP treatment decreases SHR blood pressure, improves aorta remodeling and renal protection, and that this effect could be attributable, in part, due to antioxidant and vascular tone improvement.

The ratoon rice planting area is gradually expanding, and decreasing Cadmium (Cd) accumulation in ratoon rice is important for food safety and human health. In this study, conventional indica rice (HHZ, Huanghuazhan), three-line indica–japonica hybrid rice (YY-4149, Yongyou 4149), and two-line indica hybrid rice (LY-121, Liangyou 121) were compared regarding ratoon rice yield and Cd uptake, transport, and accumulation. The distribution of Cd at different nodes in the ratoon crop was also examined. The rank-order of the Cd contents in each part (root, stem, leaf, stubble, and spike) of the main and ratoon crops of the tested cultivars was HHZ > LY-121 > YY-4149. The rank-order of the Cd content in each plant part at different nodes in the ratoon crop was HHZ > LY-121 > YY-4149. The Cd content in each plant part increased as the node position (i.e., according to the germination position of regenerated seedlings, the nodes are divided into the second, third, and fourth or fifth node from the top in stubble) was lowered. The redundancy analysis indicated that the low-node brown rice Cd content had the largest effect on the total brown rice Cd content in the ratoon crop. Accordingly, indica–japonica hybrid cultivars should be selected for the production of ratoon rice in mildly Cd-polluted areas, and the height of the main crop stubble should be maximized during harvest.

Abstract Background The purpose of this study is to investigate the performance and fracture resistance of different resin-matrix ceramic materials for use in implant-supported single crowns with respect to the abutment design (crown thickness: 1 mm, 2 and 3 mm). Methods Forty-eight abutments and crowns were fabricated on implants in the right lower first molar. Two resin-matrix ceramic materials for dental crowns were selected for study: (1) a glass-ceramic in a resin interpenetrating matrix (Vita Enamic, Vita, Germany) and (2) a resin-based composite with nanoparticle ceramic filler (Lava Ultimate, 3 M ESPE, USA). Three types of abutments were designed: 1 mm thick crown + custom titanium abutment, 2 mm thick crown + custom titanium abutment and 3 mm thick crown + prefabricated titanium abutment. The experiment was divided into 6 groups (n = 8) according to the crown materials and abutment designs. After 10,000 thermocycles, fracture resistance was measured using a universal testing machine. The statistical significance of differences between various groups were analysed with ANOVA followed by a post hoc Tukey’s honestly significant difference test. The surfaces of the fractured specimens were examined with scanning electron microscopy (SEM). Results Two-way ANOVA revealed that the abutment design (F = 28.44, P = 1.52 × 10− 8

Abstract Background The treatment of high‐risk B‐cell lymphoma (BCL) remains a challenge, especially in the elderly. Methods A total of 83 patients (median age 65 years), who have achieved a complete response after induction therapy, were divided into two groups: R2 + GM‐CSF regimen (lenalidomide, rituximab, granulocyte‐macrophage colony‐stimulating factor [GM‐CSF]) as maintenance therapy (n = 39) and observation (n = 44). The efficacy of the R2 + GM‐CSF regimen as maintenance in patient with high‐risk BCL was analyzed and compared with observation. Results The number of natural killer cells in patients increased after R2 + GM‐CSF regimen administration (0.131 × 109/L vs. 0.061 × 109/L, p = 0.0244). Patients receiving the R2 + GM‐CSF regimen as maintenance therapy had longer remission (duration of response: 18.9 vs. 11.3 months, p = 0.001), and longer progression‐free survival (not reached (NR) vs. 31.7 months, p = 0.037), and overall survival (OS) (NR vs. NR, p = 0.015). The R2 + GM‐CSF regimen was safe and well tolerated. High international prognostic index score (p = 0.012), and high tumor burden (p = 0.005) appeared to be independent prognostic factors for worse PFS. Conclusions The maintenance therapy of R2 + GM‐CSF regimen may improve survival in high‐risk BCL patients, which might be modulated by amplification of natural killer cells. The efficacy of the R2 + GM‐CSF maintenance regimen has to be further validated in prospective random clinical trials.

Abstract Background Brain-derived neurotrophic factor (BDNF) plays an important role in ovarian function including follicle development and oocyte maturation, and embryonic development. However, whether BDNF treatment can reimpose ovarian aging and impaired fertility remains elusive. In this study, we investigated the reproductive outcomes of BDNF treatment and potential mechanisms in aged mice. Method “Aged” mice (35–37 weeks old, n = 68) were treated with recombinant human BDNF protein (rhBDNF, 1 µg/200 µL) through daily intraperitoneal (IP) injection for 10 days with/without ovulation induction. Reproductive age mice (8–10 weeks old, n = 28) were treated with ANA 12 (a selective BDNF receptor, TrkB antagonist) through daily IP injection for 5 days with/without ovulation induction. Ovarian function was assessed by ovarian weight, number of follicles, and sex hormone productions. Following induction of ovulation, the number of total oocytes or abnormal oocytes, and blastocyst formation were assessed. Reproductive functions of the mice were evaluated, including pregnancy rate, mating duration for conception, implantation sites, litter size, and weight of offspring. Finally, the molecular mechanism of the effects of BDNF on ovarian cell functions in mice were examined by Western blot and immunofluorescence. Results rhBDNF treatment increased the ovarian weight, number of follicles, number and quality of oocytes including increased blastocysts formation, blood estrogen levels, and pregnancy rate in 35-37-week-old mice. Conversely, BDNF receptor antagonist, ANA 12, treatment decreased the ovarian volume and number of antral follicles and increased the proportion of abnormal oocytes in 8-10-week-old mice. We further demonstrated that BDNF treatment promoted ovarian cell proliferation as well as activation of TrkB and cyclinD1-creb signalling. Conclusion We demonstrated that ten consecutive days of daily IP injection of rhBDNF rescued ovarian function in aged mice. Our results further indicate that TrkB and cyclin D1-creb signaling may underlie the BDNF function in ovaries. Targeting BDNF-TrkB signaling is a potential novel therapeutic strategy to reverse ovarian aging.

Abstract Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is currently the standard first-line therapy for EGFR-mutated advanced non-small cell lung cancer (NSCLC). The life quality and survival of this subgroup of patients were constantly improving owing to the continuous iteration and optimization of EGFR-TKI. Osimertinib, an oral, third-generation, irreversible EGFR-TKI, was initially approved for the treatment of NSCLC patients carrying EGFR T790M mutations, and has currently become the dominant first-line targeted therapy for most EGFR mutant lung cancer. Unfortunately, resistance to osimertinib inevitably develops during the treatment and therefore limits its long-term effectiveness. For both fundamental and clinical researchers, it stands for a major challenge to reveal the mechanism, and a dire need to develop novel therapeutics to overcome the resistance. In this article, we focus on the acquired resistance to osimertinib caused by EGFR mutations which account for approximately 1/3 of all reported resistance mechanisms. We also review the proposed therapeutic strategies for each type of mutation conferring resistance to osimertinib and give an outlook to the development of the next generation EGFR inhibitors. Video Abstract

FOXD1, a new member of the FOX transcription factor family, serves as a mediator and biomarker for cell reprogramming. But its contribution to prognosis of uveal melanoma (UVM) is unclear. This study demonstrated that FOXD1 might promote tumor growth and invasion, because FOXD1 expression was negatively correlated with overall survival, progression-free survival, and disease-specific survival in UVM patients. This conjecture was verified in cell culture with human uveal melanoma cell line (MUM2B) as model cells. Additionally, the biological mechanisms of FOXD1 based on FOXD1-related genomic spectrum, molecular pathways, tumor microenvironment, and drug treatment sensitivity were examined using The Cancer Genome Atlas (TCGA) database, aiming to reasonably explain why FOXD1 leads to poor prognosis of UVM. On these bases, a novel tumor prognostic model was established using the FOXD1-related immunomodulators TMEM173, TNFRSF4, TNFSF13, and ULBP1, which will enable the stratification of disease seriousness and clinical treatment for patients.

Huangqi Chifeng Decoction (HQCFT), a traditional Chinese medicine preparation, has long been used to treat cardiovascular and cerebrovascular diseases. However, the mechanism of the beneficial effect of HQCFT on atherosclerosis remains to be explored. In this work, to investigate the effects of HQCFT on bile acid (BA) metabolism and the gut microbiome in atherosclerosis, ApoE−/− mice were fed a with high-fat diet for 16 weeks to establish the AS model. HQCFT(1.95 g kg−1 and 3.9 g kg−1 per day) was administered intragastrically for 8 weeks to investigate the regulatory effects of HQCFT on gut microbiota and bile acid metabolism and to inhibit the occurrence and development of AS induced by a high-fat diet. Histopathology, liver function and blood lipids were used to assess whether HQCFT can reduce plaque area, regulate lipid levels and alleviate liver steatosis in AS mice. In addition, 16S rDNA sequencing was used to screen the gut microbiota structure, and ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC‒MS/MS) was used to determine the bile acid profile. The mRNA and protein expression levels of bile acid metabolism were detected by RT‒PCR and WB to find the potential correlation. Results: HQCFT can regulate gut microbiota disorders, which was achieved by increasing gut microbiota diversity and altering Proteobacteria, Desulfobacterota, Deferribacteres, Rodentibacter, Parasutterella, and Mucispirillum interference abundance to improve AS-induced gut microbiota. HQCFT can also adjust the content of bile acids (TCA, LCA, DCA, TDCA, TLCA, UDCA, etc.), regulate bile acid metabolism, relieve liver fat accumulation, and inhibit the process of AS. In addition, HQCFT can restore the abnormal metabolism of bile acid caused by AS by regulating the expression of farnesoid X receptor (FXR), liver X receptor α (LXRα), ABCA1, ABCG1 and CYP7A1. Conclusion: HQCFT may play a part in the prevention of atherosclerosis by inhibiting the FXR/LXRα axis, increasing the expression of CYP7A1 in the liver, and regulating the interaction between the gut microbiota and bile acid metabolism.

While existing research has illuminated the environmental dangers and neurotoxic effects of MC-LR exposure, the molecular underpinnings of brain damage from environmentally-relevant MC-LR exposure remain elusive. Employing a comprehensive approach involving RNA sequencing, histopathological examination, and biochemical analyses, we discovered genes differentially expressed and enriched in the ferroptosis pathway. This finding was associated with mitochondrial structural impairment and downregulation of Gpx4 and Slc7a11 in mice brains subjected to low-dose MC-LR over 180 days. Mirroring these findings, we noted reduced cell viability and GSH/GSSH ratio, along with an increased ROS level, in HT-22, BV-2, and bEnd.3 cells following MC-LR exposure. Intriguingly, MC-LR also amplified phospho-Erk levels in both in vivo and in vitro settings, and the effects were mitigated by treatment with PD98059, an Erk inhibitor. Taken together, our findings implicate the activation of the Erk/MAPK signaling pathway in MC-LR-induced ferroptosis, shedding valuable light on the neurotoxic mechanisms of MC-LR. These insights could guide future strategies to prevent MC-induced neurodegenerative diseases.

Abstract Bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) are among the most common morbidities affecting extremely premature infants who receive oxygen therapy. Many clinical studies indicate that BPD is associated with advanced ROP. However, the mechanistic link between hyperoxia, BPD, and ROP remains to be explored. Gasdermin D (GSDMD) is a key executor of inflammasome-induced pyroptosis and inflammation. Inhibition of GSDMD has been shown to attenuate hyperoxia-induced BPD and brain injury in neonatal mice. The objective of this study was to further define the mechanistic roles of GSDMD in the pathogenesis of hyperoxia-induced BPD and ROP in mouse models. Here we show that global GSDMD knockout (GSDMD-KO) protects against hyperoxia-induced BPD by reducing macrophage infiltration, improving alveolarization and vascular development, and decreasing cell death. In addition, GSDMD deficiency prevented hyperoxia-induced ROP by reducing vasoobliteration and neovascularization, improving thinning of multiple retinal tissue layers, and decreasing microglial activation. RNA sequencing analyses of lungs and retinas showed that similar genes, including those from inflammatory, cell death, tissue remodeling, and tissue and vascular developmental signaling pathways, were induced by hyperoxia and impacted by GSDMD-KO in both models. These data highlight the importance of GSDMD in the pathogenesis of BPD and ROP and suggest that targeting GSDMD may be beneficial in preventing and treating BPD and ROP in premature infants.

A novel zero-reference low-light image-enhancement approach based on noise estimation (ZLEN) is proposed to mitigate noise interference in image-enhancement processes, while the tenets of zero-reference and lightweight network architecture are maintained. ZLEN improves the high-order curve expression governing the mapping of low-light images to their enhanced counterparts, addressing image noise through a meticulously designed noise-estimation module and a zero-reference noise loss function. First, the higher-order curve expression with a noise term is defined, and then the noise map undergoes feature extraction through the semantic-aware attention module; following this, the resulting features are integrated with the low-light image. Ultimately, a lightweight convolutional neural network is adjusted to estimate higher-order curve parameters that link the low-light image to its enhanced version. Notably, ZLEN achieves luminance enhancement and noise reduction without paired or unpaired training data. Rigorous qualitative and quantitative evaluations were conducted on diverse benchmark datasets, demonstrating that ZLEN attained state-of-the-art (SOAT) status among existing zero-reference and unpaired-reference image-enhancement methodologies, while it exhibited comparable performance to full-reference image-enhancement methods. To confirm the practicality and robustness of ZLEN, the luminance enhancement was applied to mine images, which yielded satisfactory results.

The physics potential of detecting ^8 B solar neutrinos will be exploited at the Jiangmen Underground Neutrino Observatory (JUNO), in a model-independent manner by using three distinct channels of the charged current (CC), neutral current (NC), and elastic scattering (ES) interactions. Due to the largest-ever mass of ^13 C nuclei in the liquid scintillator detectors and the expected low background level, ^8 B solar neutrinos are observable in the CC and NC interactions on ^13 C for the first time. By virtue of optimized event selections and muon veto strategies, backgrounds from the accidental coincidence, muon-induced isotopes, and external backgrounds can be greatly suppressed. Excellent signal-to-background ratios can be achieved in the CC, NC, and ES channels to guarantee the observation of the ^8 B solar neutrinos. From the sensitivity studies performed in this work, we show that JUNO, with 10 yr of data, can reach the 1 σ precision levels of 5%, 8%, and 20% for the ^8 B neutrino flux, ${\sin }^{2}{\theta }_{12}$ , and ${\rm{\Delta }}{m}_{21}^{2}$ , respectively. Probing the details of both solar physics and neutrino physics would be unique and helpful. In addition, when combined with the Sudbury Neutrino Observatory measurement, the world's best precision of 3% is expected for the measurement of the ^8 B neutrino flux.

The coronavirus disease-19 (COVID-19) pandemic, declared in early 2020, has left an indelible mark on global health, with over 7.0 million deaths and persistent challenges. While the pharmaceutical industry raced to develop vaccines, the emergence of mutant severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) strains continues to pose a significant threat. Beyond the immediate concerns, the long-term health repercussions of COVID-19 survivors are garnering attention, particularly due to documented cases of cardiovascular issues, liver dysfunction, pulmonary complications, kidney impairments, and notable neurocognitive deficits. Recent studies have delved into the pathophysiological changes in various organs following post-acute infection with murine hepatitis virus-1 (MHV-1), a coronavirus, in mice. One aspect that stands out is the impact on the skin, a previously underexplored facet of long-term COVID-19 effects. The research reveals significant cutaneous findings during both the acute and long-term phases post-MHV-1 infection, mirroring certain alterations observed in humans post-SARS-CoV-2 infection. In the acute stages, mice exhibited destruction of the epidermal layer, increased hair follicles, extensive collagen deposition in the dermal layer, and hyperplasticity of sebaceous glands. Moreover, the thinning of the panniculus carnosus and adventitial layer was noted, consistent with human studies. A long-term investigation revealed the absence of hair follicles, destruction of adipose tissues, and further damage to the epidermal layer. Remarkably, treatment with a synthetic peptide, SPIKENET (SPK), designed to prevent Spike glycoprotein-1 binding with host receptors and elicit a potent anti-inflammatory response, showed protection against MHV-1 infection. Precisely, SPK treatment restored hair follicle loss in MHV-1 infection, re-architected the epidermal and dermal layers, and successfully overhauled fatty tissue destruction. These promising findings underscore the potential of SPK as a therapeutic intervention to prevent long-term skin alterations initiated by SARS-CoV-2, providing a glimmer of hope in the battle against the lingering effects of the pandemic.

Neuropathic pain (NP) is known to be associated with abnormal changes in specific brain regions, but the complex neural network behind it is vast and complex and lacks a systematic summary. With the help of various animal models of NP, a literature search on NP brain regions and circuits revealed that the related brain nuclei included the periaqueductal gray (PAG), lateral habenula (LHb), medial prefrontal cortex (mPFC), and anterior cingulate cortex (ACC); the related brain circuits included the PAG-LHb and mPFC-ACC. Moreover, acupuncture and injurious information can affect different brain regions and influence brain functions via multiple aspects to play an analgesic role and improve synaptic plasticity by regulating the morphology and structure of brain synapses and the expression of synapse-related proteins; maintain the balance of excitatory and inhibitory neurons by regulating the secretion of glutamate, γ-aminobutyric acid, 5-hydroxytryptamine, and other neurotransmitters and receptors in the brain tissues; inhibit the overactivation of glial cells and reduce the release of pro-inflammatory mediators such as interleukins to reduce neuroinflammation in brain regions; maintain homeostasis of glucose metabolism and regulate the metabolic connections in the brain; and play a role in analgesia through the mediation of signaling pathways and signal transduction molecules. These factors help to deepen the understanding of NP brain circuits and the brain mechanisms of acupuncture analgesia.

Abstract Main goal of the JUNO experiment is to determine the neutrino mass ordering using a 20 kt liquid-scintillator detector. Its key feature is an excellent energy resolution of at least 3% at 1 MeV, for which its instruments need to meet a certain quality and thus have to be fully characterized. More than 20,000 20-inch PMTs have been received and assessed by JUNO after a detailed testing program which began in 2017 and elapsed for about four years. Based on this mass characterization and a set of specific requirements, a good quality of all accepted PMTs could be ascertained. This paper presents the performed testing procedure with the designed testing systems as well as the statistical characteristics of all 20-inch PMTs intended to be used in the JUNO experiment, covering more than fifteen performance parameters including the photocathode uniformity. This constitutes the largest sample of 20-inch PMTs ever produced and studied in detail to date, i.e. 15,000 of the newly developed 20-inch MCP-PMTs from Northern Night Vision Technology Co. (NNVT) and 5000 of dynode PMTs from Hamamatsu Photonics K. K.(HPK).

The anti-seismic support and hanger are firmly connected to the building structure and are anti-seismic support equipment with seismic force as the main load. Real-time and accurate acquisition of the service status of the seismic support and hanger to check and judge whether the seismic support and hanger are in a normal working state is of great significance for practical engineering applications. In this paper, based on distributed sensor technology, a set of intelligent monitoring systems for seismic support and hanger of buildings is established. The sensing equipment installed on the seismic support and hanger senses the signal, and then the data collection, storage and processing are used to accurately judge the seismic support and hanger. Service performance status. To effectively fuse multi-source data in distributed sensor environment, an improved method based on wavelet and neural network data fusion is proposed. Compared with the existing methods, the experimental results show that the proposed method has good robustness. Besides, it has better performance in building seismic multi-source monitoring data fusion and is less affected by the data overlap ratio.

Abstract Background This research aimed to explore feasibility and the time required when erbium-doped yttrium aluminum garnet (Er:YAG) laser as a non-invasive treatment modality to retrieve different thicknesses of zirconia material bonded by two dental cements from titanium implant abutments. Methods Prepared 80 titanium blocks (length: 20 mm, width: 10 mm, height: 10 mm) and square zirconia sheets (length: 10 mm) with different thicknesses (1 mm, 2 mm, 3 mm, and 4 mm) were 20 pieces each. Resin modified glass ionomer cement (RelyX Luting 2; RXL) and resin cement (Clearfil SA luting; CSL) were used to bond zirconia sheet and titanium block. Specimens were kept in 100% humidity for 48 h. Er:YAG laser was used to retrieve the zirconia sheet and recorded the time. Universal testing machine was used to measure the residual adhesion of the samples that did not retrieve after 5 min of laser irradiation. Shear bond strength (MPa) and the time data (s) were analyzed using Kruskal–Wallis Test. The bonding surface and the irradiation surface of the zirconia sheet was examined with the scanning electron microscopy (SEM). Results Within 5 min of laser irradiation, RXL group: 1 mm group all fell off, 2 mm group had 3 specimens did not fall off, there was no statistical difference in the average time between the two groups; CSL group: half of the 1 mm group fell off. Shear bond strength test results: there was no statistical difference between 1 and 2 mm in RXL group and 1 mm in CSL group, there was no statistical difference between 3 mm in RXL group and 2 mm in CSL group, and there were significant differences statistically in comparison between any two groups in the rest. SEM inspection showed that the bonding surface and the irradiation surface of the zirconia sheet had changes. Conclusion In this vitro study, the following could be concluded: it is faster to remove zirconia crowns with thickness less than 2 mm from titanium abutment when luted with RelyX Luting 2 compared to Clearfil SA luting.

The advent of topological semi-metals with peculiar band structure and exotic quantum-transport provides novel pathways for upgrading the performance of terahertz (THz) detection. HgTe is among such a candidate with the unique advantages of a negative bandgap, ultra-high mobility, and thermoelectricity, which ignites the possibility of addressing the technical bottlenecks of traditional routes for THz detection. Herein, for the first time, we report large-area (3 in.) growth of high-mobility HgTe thin-film via molecular-beam epitaxial and the implementation of bow-tie antennas based HgTe THz-detector with the abilities of ultrafast response, low noise, and high ambient-stability at room temperature. By exploration of strong light-coupling and superior hot-carrier transport, the bow-tie antenna-based HgTe photodetector can achieve a responsivity of 0.04 A/W and a noise equivalent power of less than 0.6 nW/Hz1/2 at 0.3 THz. Furthermore, the sensitivity can be further improved by nearly an order of magnitude up to 0.36 A/W at 0.3 THz by incorporating a short channel asymmetric cubic resonator. The reported performances allow a realistic exploration of high-mobility bulk states in topological semimetals for large area, fast-imaging applications in the THz band.

Abstract We study damping signatures at the Jiangmen Underground Neutrino Observatory (JUNO), a medium-baseline reactor neutrino oscillation experiment. These damping signatures are motivated by various new physics models, including quantum decoherence, ν 3 decay, neutrino absorption, and wave packet decoherence. The phenomenological effects of these models can be characterized by exponential damping factors at the probability level. We assess how well JUNO can constrain these damping parameters and how to disentangle these different damping signatures at JUNO. Compared to current experimental limits, JUNO can significantly improve the limits on τ 3/m 3 in the ν 3 decay model, the width of the neutrino wave packet σ x , and the intrinsic relative dispersion of neutrino momentum σ rel.

Abstract Traditional calibration technology has been widely used in measurement and monitoring; however, there are limitations of poor calibration accuracy, which can not meet the accuracy requirements in some scenarios. About this problem, we proposed a grey wolf optimization algorithm based on levy flight and mutation mechanism to solve camera internal parameters in this paper. The algorithm is based on the actual nonlinear model, which takes the minimum average value of reprojection error as the objective function. The grey wolf position is randomly generated within a given range. Then, the grey wolf optimization algorithm based on levy flight and mutation mechanism is used to iteratively calculate the optimal position, which is the internal parameters of cameras. The two groups of experimental data were performed to verify the algorithm. The result shows better effectiveness and calibration accuracy of the proposed algorithm compared with other optimization methods.

Abstract Semiconductor nanowires (NWs) could simultaneously provide gain medium and optical cavity for performing nanoscale lasers with easy integration, ultracompact footprint, and low energy consumption. Here, we report III–V semiconductor NW lasers can also be used for self-frequency conversion to extend their output wavelengths, as a result of their non-centrosymmetric crystal structure and strongly localized optical field in the NWs. From a GaAs/In0.16Ga0.84As core/shell NW lasing at 1016 nm, an extra visible laser output at 508 nm is obtained via the process of second-harmonic generation, as confirmed by the far-field polarization dependence measurements and numerical modeling. From another NW laser with a larger diameter which supports multiple fundamental lasing wavelengths, multiple self-frequency-conversion lasing modes are observed due to second-harmonic generation and sum-frequency generation. The demonstrated self-frequency conversion of NW lasers opens an avenue for extending the working wavelengths of nanoscale lasers, even to the deep ultraviolet and THz range.

Introduction: A combination of deep eutectic solvent with ethanol was developed for pretreatment of Broussonetia papyrifera to effectively extract lignin and promote the subsequent enzymatic hydrolysis.Methods: In order to further explore the optimal conditions for enzymatic hydrolysis, a central composite design method was applied.Results and Discussion: The correlation between each factor and glucose yield was obtained, and the optimal conditions was 160°C, 60 min, the ratio of DES to E was 1/1 (mol/mol). The results showed that compared with control, the glucose yield increased by 130.67% under the optimal pretreatment conditions. Furthermore, the specific surface area of biomass was increased by 66.95%, and the content of xylan and lignin was decreased by 86.71% and 85.83%. The correlation between xylan/lignin removal and enzymatic hydrolysis showed that the removal of lignin facilitated the glucose yield more significantly than that of xylan. To further explore the lignin valorization, the structural and antioxidant analysis of recovered lignin revealed that high temperature was favorable for lignin with good antioxidant performance. This pretreatment is a promising method for separating lignin with high antioxidant activity and improving cellulose digestibility.

Background: Zhijing Powder (ZJP) is a traditional Chinese medicine containing two kinds of Chinese medicine. Those studies analyze the molecular mechanism of ZJP in treating hypertension through network pharmacology, combined with animal experiments. Methods: First, the effective ingredients and potential targets of the drug were obtained through drug databases, while the targets of disease obtained through disease target databases. The potential targets, cellular bioanalysis and signaling pathways were found in some platforms by analyzing collected targets. Further experiments were conducted to verify the effect and mechanism of drugs on cold and high salt in an induced-hypertension rat model. Results: There are 17 effective components of centipedes and 10 of scorpions, with 464 drug targets obtained after screening. A total of 1263 hypertension targets were obtained after screening and integration, resulting in a protein-protein interaction network (PPI) with 145 points and 1310 edges. Gene ontology (GO) analysis shows that blood circulation regulation and activation of G protein-coupled receptors are mainly biological processes. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis shows that neuroactive ligand-receptor interaction, calcium signaling pathways, PI3K-AKT signaling pathways are the most abundant gene-enriched pathway. Animal experiments indicated that ZJP can reduce blood pressure (BP), affect expression of the PI3K-AKT signaling pathway, and improve oxidative stress in the body. Conclusion: ZJP ameliorates oxidative stress and reduces BP in hypertensive rats caused by cold stimuli and high salt, revealing its effect on the expression of the PI3K/AKT signaling pathway in the rat aorta.

Antibiotic resistance genes (ARGs) are a new environmental contaminant that poses a major hazard to humans and the environment. This research discusses the methods and drawbacks of two ARG removal approaches, constructed wetlands (CWs) and photocatalysis. CWs primarily rely on the synergistic effects of substrate adsorption, plant uptake, and microbial processes to remove ARGs. The removal of ARGs can be influenced by wetland plants, substrate type, wetland type, and hydraulic conditions. The absolute abundance of ARGs in effluent decreased, but their relative abundance increased. Photocatalysis deactivates ARGs predominantly through reactive oxygen species, with removal effectiveness determined by catalyst type, radiation type, and radiation intensity. The drawback is that it exposes intracellular resistance genes, perhaps increasing the risk of ARG spread. To address the current shortcomings, this paper proposes the feasibility of combining a constructed wetland with photocatalysis technology, which provides a novel strategy for ARG removal.

Baicalin (BA) is among the most effective and abundant flavonoids extracted from Scutellaria baicalensis that may be utilized to treat diseases associated with hepatic fibrosis (HF). Through network pharmacology, gut microbiota, and experimental validation, this research intends to elucidate the multi-target mechanism of BA on HF. BA targets were screened using databases and literature. As a result, In the anti-HF mechanism, the BA and 191 HF-associated targets interact, with 9 specific targets indicating that the BA’s anti-HF mechanism is closely linked to gut microbiota. Consequently, rat intestinal content samples were obtained and examined using 16S rRNA sequencing. In the BA-treated group, the gut microbiota was positively regulated at the phylum,and genus levels, with Lactobacillus performing significantly. The study concluded that BA has a multi-targeted anti-HF effect and has changed the gut microbial ecosystem.

Base on the precipitation forecast of ECWMF model from 2016 to 2019 and the observation data, five schemes are designed to carry out revision experiment on numerical model clear-rainy forecast, including Optimal Percentile (OP), the Optimal Threat Score (OTS), the Probability Matching (PM), the sub-district OTS and the sub-district PM-OTS fusion scheme. The results show that: (1) The clear-rainy revised thresholds of OP and PM are static, and that of OTS is dynamic. The thresholds of the 5 schemes are all applicable to Area A(basin, northern Aba Prefecture and northern Garze Prefecture), among which the thresholds of PM and sub-district PM-OTS are more applicable to Area B(southern Ganzi Prefecture and panxi area) with obvious wet deviation of the numerical model. (2) Each scheme has obvious revised ability for ECWMF model clear-rainy forecast. The revised effect of 24 h is the best, and that of Area B is superior to Area B, autumn and winter is better than spring and summer. (3) Revised scheme scores after subdivision are better than before, and the sub-district PM-OTS is the best. Individual cases and batch tests show that the revised effects of the schemes in Area A are comparable, the rainfall distribution in Area B are more close to the observed precipitation after revised of PM, sub-district OTS and PM-OTS fusion schemes, among which the sub-district PM-OTS is the best.

Leptin is the pivotal modulator in the onset and progression of breast cancer and obesity. Celastrol, which is extracted from the roots of Tripterygium wilfordi plants, exerts various anticancer bioactivities and has recently emerged as a candidate to treat obesity by improving leptin sensitivity. However, the relationship between leptin and celastrol in the treatment of breast cancer is unknown. Here, the growth and migration of MCF-7 cells induced by leptin were tested to demonstrate the antineoplastic activity of celastrol. Transcriptomic analysis and western blotting were conducted to explore the biological roles of leptin in treating breast cancer with celastrol. The present findings showed that celastrol remarkably reversed leptin-triggered cell proliferation and migration in MCF-7 cells. Fifty-two mRNAs with fivefold higher counts and 149 mRNAs with fivefold lower counts were identified in the celastrol-treated MCF-7 cells. According to the GO and KEGG analyses, the effects of celastrol on MCF-7 cells forced lipid metabolism and the endocrine system. Moreover, leptin treatment induced phosphorylation of leptin receptor and PI3K/AKT in MCF-7 cells, whereas pretreatment with celastrol partly abrogated leptin activation. The binding of celastrol to the leptin receptor was also confirmed by molecular docking. The antitumor effect of celastrol is proposed to be mediated by its binding to the leptin receptor and controlled downregulation of the PI3K/AKT pathway.