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Precipitable water vapor (PWV) is one of the most dynamic components of the atmosphere, playing a critical role in precipitation formation, the hydrological cycle, and climate change. This study used SuomiNet Global Positioning System (GPS) data from April 2021 to June 2023 in the United States to comprehensively evaluate 3 and 6 h Global Forecast System (GFS) PWV products (i.e., PWV3h and PWV6h). There was high consistency between the GFS PWV and GPS PWV data, with correlation coefficients (Rs) higher than 0.98 and a root mean square error (RMSE) of about 0.23 cm. The PWV3h product performed slightly better than PWV6h. PWV tended to be underestimated when PWV > 4 cm, and the degree of underestimation increased with increasing water vapor value. The RMSE showed obvious seasonal and diurnal variations, with the RMSE value in summer (i.e., 0.280 cm) considerably higher than in winter (i.e., 0.158 cm), and nighttime were RMSEs higher than daytime RMSEs. Clear-sky conditions showed smaller RMSEs, while cloudy-sky conditions exhibited a smaller range of monthly RMSEs and higher Rs. PWV demonstrated a clear spatial pattern, with both Rs and RMSEs decreasing with increasing elevation and latitude. Based on these temporal and spatial patterns, Back Propagation neural network and random forest (RF) models were employed, using PWV, Julian day, and geographic information (i.e., latitude, longitude, and elevation) as input data to correct the GFS PWV products. The results indicated that the RF model was more advantageous for water vapor correction, improving overall accuracy by 12.08%. In addition, the accuracy of GFS PWV forecasts during hurricane weather was also evaluated. In this extreme weather, the RMSE of the GFS PWV forecast increased comparably to normal weather, but it remained less than 0.4 cm in most cases. [ABSTRACT FROM AUTHOR]

Aerosol research is important for the protection of the ecological environment, the improvement of air quality, and as a response to climate change. In this study, a random forest (RF) estimation model of aerosol optical depth (AOD) and extinction coefficient vertical profiles was, respectively, established using Orbiting Carbon Observatory-2 (OCO-2) oxygen-A band (O2 A-band) data from China and its surrounding areas in 2016, combined with geographical information (longitude, latitude, and elevation) and viewing angle data. To address the high number of OCO-2 O2 A-band channels, principal component analysis (PCA) was employed for dimensionality reduction. The model was then applied to estimate the aerosol extinction coefficients for the region in 2017, and its validity was verified by comparing the estimated values with the Cloud-Aerosol Lidar Infrared Pathfinder Satellite Observations (CALIPSO) Level 2 extinction coefficients. In the comprehensive analysis of overall performance, an AOD model was initially constructed using variables, achieving a correlation coefficient (R) of 0.676. Subsequently, predictions for aerosol extinction coefficients were generated, revealing a satisfactory agreement between the predicted and the actual values in the vertical direction, with an R of 0.535 and a root mean square error (RMSE) of 0.107 km−1. Of the four seasons of the year, the model performs best in autumn (R = 0.557), while its performance was relatively lower in summer (R = 0.442). Height had a significant effect on the model, with both R and RMSE decreasing as height increased. Furthermore, the accuracy of aerosol profile inversion shows a dependence on AOD, with a better accuracy when AOD is less than 0.3 and RMSE can be less than 0.06 km−1. [ABSTRACT FROM AUTHOR]

Equine influenza (EI) is a severe infectious disease that causes huge economic losses to the horse industry. Spatial epidemiology technology can explore the spatiotemporal distribution characteristics and occurrence risks of infectious diseases, it has played an important role in the prevention and control of major infectious diseases in humans and animals. For the first time, this study conducted a systematic analysis of the spatiotemporal distribution of EI using SaTScan software and investigated the important environmental variables and suitable areas for EI occurrence using the Maxent model. A total of 517 occurrences of EI from 2005 to 2022 were evaluated, and 14 significant spatiotemporal clusters were identified. Furthermore, a Maxent model was successfully established with high prediction accuracy (AUC = 0.920 ± 0.008). The results indicated that annual average ultraviolet radiation, horse density, and precipitation of the coldest quarter were the three most important environmental variables affecting EI occurrence. The suitable areas for EI occurrence are widely distributed across all continents, especially in Asia (India, Mongolia, and China) and the Americas (Brazil, Uruguay, USA, and Mexico). In the future, these suitable areas will expand and move eastward. The largest expansion is predicted under SSP126 scenarios, while the opposite trend will be observed under SSP585 scenarios. This study presents the spatial epidemiological characteristics of EI for the first time. The results could provide valuable scientific insights that can effectively inform prevention and control strategies in regions at risk of EI worldwide. [ABSTRACT FROM AUTHOR]

In order to clarify the relationship between the conventional diffusion models and the time-dependent diffusion model during gas desorption, a porous diffusion model during gas desorption in coal was established by modeling the pore structure according to the porous diffusion theory and fractal theory. Gas diffusion processes were experimentally measured using a series of coal samples with different ranks and types under different gas equilibrium pressures. And the established theoretical model was furthermore verified by experimental data. The theoretical data derived from the established porous diffusion model agreed well with the experimental data with correlation coefficients greater than 99.0%. The attenuation of diffusion coefficient during gas desorption was essentially attributed to the gradual decrease of the gas diffusion amount for large pores during unsteady diffusion of gas in porous media. The effective diffusion coefficient presented a first fast and then slow decreasing trend with the prolonged diffusion time. The diffusion coefficient increased with the increase of gas equilibrium pressure as well as the metamorphic grade and fragmentation degree of coal. The pore connectivity enhanced as the surface area proportion of larger pores increased, leading to an increase in the proportion of the gas diffusion quantity in larger pores and the diffusion coefficient and meanwhile a decrease in the fractal dimension. This study will provide theoretical support for in-depth understanding of the gas diffusion mechanism in gas-containing coal. [ABSTRACT FROM AUTHOR]

The article deals with the control of the process of rapprochement of a tether system with a passive space object (cargo, space debris, etc.) in an almost circular near-Earth orbit. It is assumed that the active spacecraft, which includes a tether system with a capture device (not deployed), is located in a close (relative to the orbit of the cargo) orbit, which was formed using some known long-range guidance algorithm. It is assumed that the active spacecraft, which includes a tether system with a capture device (not deployed), is located in a close (relative to the orbit of the cargo) orbit, which was formed using some known long-range guidance algorithm. The position of the dummy point is chosen based on the fact that, after the deployment of the tether system, the capture device appears in the vicinity of the cargo immediately or after some small portion of passive movement in orbit. The control of the process of approaching the spacecraft with a fictitious point in the spatial case is constructed using the Bellman dynamic programming principle using a linearized system. Continuous control is used with the help of jet engines with finite thrust. The components of the reactive forces for which the control is being constructed are directed along the transversal and binormal in the orbital coordinate system. It is assumed that the unavoidable guidance errors can be corrected by changing the length of the tether or in some other way. A numerical example of modeling the processes under consideration using nonlinear equations of motion is given illustrating the proposed control scheme. [ABSTRACT FROM AUTHOR]

Neuroblastoma (NB) is the most frequent solid tumor in pediatric cases, contributing to around 15% of childhood cancer-related deaths. The wideranging genetic, morphological, and clinical diversity within NB complicates the success of current treatment methods. Acquiring an in-depth understanding of genetic alterations implicated in the development of NB is essential for creating safer and more efficient therapies for this severe condition. Several molecular signatures are being studied as potential targets for developing new treatments for NB patients. In this article, we have examined the molecular factors and genetic irregularities, including those within insulin gene enhancer binding protein 1 (ISL1), dihydropyrimidinase-like 3 (DPYSL3), receptor tyrosine kinase-like orphan receptor 1 (ROR1) and murine double minute 2-tumor protein 53 (MDM2-P53) that play an essential role in the development of NB. A thorough summary of the molecular targeted treatments currently being studied in preclinical and clinical trials has been described. Recent studies of immunotherapeutic agents used in NB are also studied in this article. Moreover, we explore potential future directions to discover new targets and treatments to enhance existing therapies and ultimately improve treatment outcomes and survival rates for NB patients. [ABSTRACT FROM AUTHOR]

The mitochondrial permeability transition pore (mPTP) is a channel in the inner mitochondrial membrane whose sustained opening in response to elevated mitochondrial matrix Ca2+ concentrations triggers necrotic cell death. The molecular identity of mPTP is unknown. One proposed candidate is the mitochondrial ATP synthase, whose canonical function is to generate most ATP in multicellular organisms. Here, we present mitochondrial, cellular, and in vivo evidence that, rather than serving as mPTP, the mitochondrial ATP synthase inhibits this pore. Our studies confirm previous work showing persistence of mPTP in HAP1 cell lines lacking an assembled mitochondrial ATP synthase. Unexpectedly, however, we observe that Ca2+-induced pore opening is markedly sensitized by loss of the mitochondrial ATP synthase. Further, mPTP opening in cells lacking the mitochondrial ATP synthase is desensitized by pharmacological inhi)bition and genetic depletion of the mitochondrial cis-trans prolyl isomerase cyclophilin D as in wild-type cells, indicating that cyclophilin D can modulate mPTP through substrates other than subunits in the assembled mitochondrial ATP synthase. Mitoplast patch clamping studies showed that mPTP channel conductance was unaffected by loss of the mitochondrial ATP synthase but still blocked by cyclophilin D inhibition. Cardiac mitochondria from mice whose heart muscle cells we engineered deficient in the mitochondrial ATP synthase also demonstrate sensitization of Ca2+-induced mPTP opening and desensitization by cyclophilin D inhibition. Further, these mice exhibit strikingly larger myocardial infarctions when challenged with ischemia/reperfusion in vivo. We conclude that the mitochondrial ATP synthase does not function as mPTP and instead negatively regulates this pore. [ABSTRACT FROM AUTHOR]

This article presents the findings of a study on the correlation between renal resistive index (RRI), renal microvessel density (RMD), and fibrosis in patients with chronic kidney disease (CKD). The study found no correlation between RRI and RMD or between RRI and fibrosis across CKD stages 1 to 5. However, RRI negatively correlated with CD34 PPA-glomerulus across CKD stages 2 to 5. The study suggests that RMD may be a useful indicator of renal function in CKD patients, but further research is needed to explore the correlation between RRI and renal microvascular disease. [Extracted from the article]

Atopic dermatitis (AD) is one of the most common inflammatory skin diseases with complex pathogenesis involving epidermal barrier dysfunction, skin microbiome abnormalities and type-2-skewed immune dysregulation. Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that plays critical roles in various biological processes. However, the role of STAT3 in epidermal keratinocytes in AD remains unclear. In this study, we generated an epidermal keratinocyte-specific Stat3-deficient mouse strain (termed Stat3 cKO mice). After topical 2,4-dinitrochlorobenzene (DNCB) treatment, Stat3 cKO mice developed worsened AD-like skin inflammation with increased Ki67+ cells, decreased filaggrin and loricrin expression, and downregulated S100A9 and LL37. The dominant microbial population in Stat3 cKO mice changed from Ralstonia to Staphylococcus. DNCB-treated Stat3 cKO mice displayed more infiltrating type-2 inflammatory cells, including mast cells, eosinophils, and CD4+T cells, accompanied by increased skin IL-4 and serum IgE levels. Moreover, thymic stromal lymphopoietin (TSLP), mainly produced by keratinocytes, was highly expressed in the ear skin of Stat3 cKO mice and chemoattracted more TSLPR+ cells. TSLP blockade significantly alleviated DNCB-induced AD-like skin inflammation in Stat3 cKO mice. Thus, epidermal keratinocyte-specific STAT3 deficiency can aggravate AD-like skin inflammation in mice, possibly through TSLP dysregulation. [ABSTRACT FROM AUTHOR]

Objective: We aimed to explore the association between serum complements and kidney function of diabetic kidney disease (DKD) in Chinese patients. Methods: This is a retrospective study involving 2,441 participants. DKD was diagnosed according to the Kidney Disease: Improving Global Outcomes (KDIGO) categories. Participants were classified as stages G1-G5 by KDIGO glomerular filtration rate (GFR) categories. Effect sizes are expressed as odds ratio (OR) with 95% confidence interval (CI). Results: After balancing age, gender, systolic blood pressure (SBP), hemoglobin A1c (HbA1C), serum triglyceride (TG), and urinary albumin-to-creatinine ratio (UACR) between the G2-G5 and control groups, per 0.1 g/L increment in serum complement C3 was significantly associated with a 27.8% reduced risk of DKD at G5 stage (OR, 95% CI, P: 0.722, 0.616-0.847, <0.001) relative to the G1 stage. Conversely, per 0.1 g/L increment in serum complement C4 was associated with an 83.0-177.6% increased risk of G2-G5 stage (P<0.001). Serum complement C1q was not statistically significant compared to controls at all stages prior to or after propensity score matching. Conclusions: Our results indicate that high concentrations of serum C4 were associated with the significantly elevated risk of kidney function deterioration across all stages, and reduced serum C3 levels with an increased risk of DKD stage G5. [ABSTRACT FROM AUTHOR]

Background: Glioma is the most common primary brain tumor. Traditional treatments for glioma include surgical resection, radiotherapy, chemotherapy, and bevacizumab therapy, but their efficacies are limited. Immunotherapy provides a new direction for glioma treatment. This study aimed to summarize the knowledge structure and research hotspots of glioma immunotherapy through a bibliometric analysis. Method: Publications pertaining to glioma immunotherapy published during the period from 1st January 1990 to 27th March 2023 were downloaded from the Web of Science Core Collection (WoSCC). Bibliometric analysis and visualization were performed using the CiteSpace, VOSviewer, Online Analysis Platform of Literature Metrology, and R software. The hotspots and prospects of glioma immunotherapy research were illustrated via analyzing the countries, institutions, journals, authors, citations and keywords of eligible publications. Results: A total of 1,929 publications pertaining to glioma immunotherapy in 502 journals were identified as of 27th March 2023, involving 9,505 authors from 1,988 institutions in 62 countries. Among them were 1,285 articles and 644 reviews. Most of publications were produced by the United States. JOURNAL OF NEURO-ONCOLOGY published the majority of publications pertaining to glioma immunotherapy. Among the authors, Lim M contributed the largest number of publications. Through analyzing keyword bursts and co-cited references, immune-checkpoint inhibitors (ICIs) were identified as the research focus and hotspot. Conclusion: Using a bibliometric analysis, this study provided the knowledge structure and research hotspots in glioma immunotherapy research during the past 33 years, with ICIs staying in the current and future hotspot. Our findings may direct the research of glioma immunotherapy in the future. [ABSTRACT FROM AUTHOR]

Plant-derived exosome-like nanoparticles (PDENs) have been paid great attention in the treatment of ulcerative colitis (UC). As a proof of concept, we isolated and identified Portulaca oleracea L-derived exosome-like nanoparticles (PELNs) from edible Portulaca oleracea L, which exhibited desirable nano-size (~ 160 nm) and a negative zeta potential value (-31.4 mV). Oral administration of PELNs effectively suppressed the expressions of pro-inflammatory cytokines (TNF-α, IL-6, IL-12, and IL-1β) and myeloperoxidase (MPO), increased levels of the anti-inflammatory cytokine (IL-10), and alleviated acute colitis in dextran sulfate sodium (DSS)-induced C57 mice and IL-10−/− mice. Notably, PELNs exhibited excellent stability and safety within the gastrointestinal tract and displayed specific targeting to inflamed sites in the colons of mice. Mechanistically, oral administration of PELNs played a crucial role in maintaining the diversity and balance of gut microbiota. Furthermore, PELNs treatment enhanced Lactobacillus reuteri growth and elevated indole derivative levels, which might activate the aryl-hydrocarbon receptor (AhR) in conventional CD4+ T cells. This activation downregulated Zbtb7b expression, leading to the reprogramming of conventional CD4+ T cells into double-positive CD4+CD8+T cells (DP CD4+CD8+ T cells). In conclusion, our findings highlighted the potential of orally administered PELNs as a novel, natural, and colon-targeted agent, offering a promising therapeutic approach for managing UC. Schematic illustration of therapeutic effects of oral Portulaca oleracea L -derived natural exosome-like nanoparticles (PELNs) on UC. PELNs treatment enhanced Lactobacillus reuteri growth and elevated indole derivative levels, which activate the aryl-hydrocarbon receptor (AhR) in conventional CD4+ T cells leading to downregulate the expression of Zbtb7b, reprogram of conventional CD4+ T cells into double-positive CD4+CD8+T cells (DP CD4+CD8+ T cells), and decrease the levels of pro-inflammatory cytokines. [ABSTRACT FROM AUTHOR]

Aging and replicative cellular senescence are associated with the reduced therapeutic potential of mesenchymal stem cells (MSCs) on a variety of diseases. This study aimed to determine the mechanism in MSC senescence and further explore a modification strategy to reverse senescence-associated cell dysfunction to improve the therapeutic efficacy of MSCs on acute liver failure (ALF). We found that the adipose tissue-derived MSCs from old mice (oAMSCs) exhibited senescence phenotypes and showed reduced therapeutic efficacy in lipopolysaccharide and D-galactosamine-induced ALF, as shown by the increased hepatic necrosis, liver histology activity index scores, serum liver function indicator levels, and inflammatory cytokine levels. The expression of miR-17-92 cluster members, especially miR-17 and miR-20a, was obviously decreased in oAMSCs and replicatively senescent AMSCs, and was consistent with the decreased oncogene c-Myc level during AMSC senescence and may mediate cMyc stemness addiction. Further experiments revealed that c-Myc-regulated miR-17-92 expression contributed to increased p21 expression and redox system dysregulation during AMSC senescence. Furthermore, modification of AMSCs with the two key miRNAs in the miR-17-92 cluster mentioned above reversed the senescence features of oAMSCs and restored the therapeutic effect of senescent AMSCs on ALF. In conclusion, the cellular miR-17-92 cluster level is correlated with AMSC senescence and can be used both as an index for evaluating and as a modification target for improving the therapeutic potential of AMSCs. NEW & NOTEWORTHY We reported for the first time that c-Myc-regulated miR-17-92 contributed to increased p21 expression and redox system dysregulation during AMSC senescence and was associated with the reduced therapeutic effects of senescent AMSCs on ALF. Moreover, modifying the expression of the miR-17-92 cluster members, especially miR-17 and/or miR-20a, could reverse AMSC senescence. Thus, miR-17-92 cluster can be used both as an index for evaluating and as a modification strategy for improving the therapeutic potential of AMSCs. [ABSTRACT FROM AUTHOR]

In this study, comparing multiple models of machine learning, a multiple linear regression (MLP), multilayer feed-forward artificial neural network (BP) model, and a radial-basis feed-forward artificial neural network (RBF-BP) model are selected for the optimization of the thermal properties of TiO2/water nanofluids. In particular, the least squares support vector machine (LS-SVM) method and radial basis support vector machine (RB-SVM) method are implemented. First, curve fitting is performed by means of multiple linear regression in order to obtain bivariate correlation functions for thermal conductivity and viscosity of the nanofluid. Then the aforementioned models are used for a predictive analysis of the dependence of its thermal conductivity and viscosity on temperature and volume fraction. The results show that the least squares support vector machine (LS-SVM) has a prediction accuracy higher than the other models. The model predicts the thermal conductivity of TiO2/water MSE = 1.0853 × 10-6, R² = 0.99864, MAE = 0.00092, RMSE = 0.00104, and the viscosity of TiO2/ water MSE = 8.1397 × 10-6, R²= 0.99995, MAE = 0.00074, RMSE = 0.0009. [ABSTRACT FROM AUTHOR]

Messenger RNA (mRNA) holds great potential in developing immunotherapy, protein replacement, and genome editing. In general, mRNA does not have the risk of being incorporated into the host genome and does not need to enter the nucleus for transfection, and it can be expressed even in nondividing cells. Therefore, mRNA‐based therapeutics provide a promising strategy for clinical treatment. However, the efficient and safe delivery of mRNA remains a crucial constraint for the clinical application of mRNA therapeutics. Although the stability and tolerability of mRNA can be enhanced by directly retouching the mRNA structure, there is still an urgent need to improve the delivery of mRNA. Recently, significant progress has been made in nanobiotechnology, providing tools for developing mRNA nanocarriers. Nano‐drug delivery system is directly used for loading, protecting, and releasing mRNA in the biological microenvironment and can be used to stimulate the translation of mRNA to develop effective intervention strategies. In the present review, we summarized the concept of emerging nanomaterials for mRNA delivery and the latest progress in enhancing the function of mRNA, primarily focusing on the role of exosomes in mRNA delivery. Moreover, we outlined its clinical applications so far. Finally, the key obstacles of mRNA nanocarriers are emphasized, and promising strategies to overcome these obstacles are proposed. Collectively, nano‐design materials exert functions for specific mRNA applications, provide new perception for next‐generation nanomaterials, and thus revolution of mRNA technology. [ABSTRACT FROM AUTHOR]

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Bacteria form a highly complex ecosystem in the gastrointestinal (GI) tract. In recent years, mounting evidence has shown that bacteria can release nanoscale phospholipid bilayer particles that encapsulate nucleic acids, proteins, lipids, and other molecules. Extracellular vesicles (EVs) are secreted by microorganisms and can transport a variety of important factors, such as virulence factors, antibiotics, HGT, and defensive factors produced by host eukaryotic cells. In addition, these EVs are vital in facilitating communication between microbiota and the host. Therefore, bacterial EVs play a crucial role in maintaining the GI tract's health and proper functioning. In this review, we outlined the structure and composition of bacterial EVs. Additionally, we highlighted the critical role that bacterial EVs play in immune regulation and in maintaining the balance of the gut microbiota. To further elucidate progress in the field of intestinal research and to provide a reference for future EV studies, we also discussed the clinical and pharmacological potential of bacterial EVs, as well as the necessary efforts required to understand the mechanisms of interaction between bacterial EVs and gut pathogenesis. [ABSTRACT FROM AUTHOR]

As double membrane-encapsulated nanovesicles (30-150 nm), exosomes (Exos) shuttle between different cells to mediate intercellular communication and transport active cargoes of paracrine factors. The anti-inflammatory and immunomodulatory activities of mesenchymal stem cell (MSC)-derived Exos (MSC-Exos) provide a rationale for novel cell-free therapies for inflammatory bowel disease (IBD). Growing evidence has shown that MSC-Exos can be a potential candidate for treating IBD. In the present review, we summarized the most critical advances in the properties of MSC-Exos, provided the research progress of MSC-Exos in treating IBD, and discussed the molecular mechanisms underlying these effects. Collectively, MSC-Exos had great potential for cell-free therapy in IBD. However, further studies are required to understand the full dimensions of the complex Exo system and how to optimize its effects. [ABSTRACT FROM AUTHOR]

HIV infection has been reported to cause bone loss and a higher risk of fracture. Under normal conditions, bone metabolism is regulated by mesenchymal cells, osteoclasts differentiated from mononuclear macro-phages, osteoblasts, and their expression of regulatory factors, such as receptor activator of nuclear factor-kappa B ligand (RANKL), M-SCF, and transforming growth factor-beta. The balance between bone resorption and osteogenesis depends on the balance between osteoclasts and osteoblasts. In addition, some immune cells, such as B-cells, T-cells, and other non-immune cells expressing RANKL, can contribute to osteoporosis under inflammatory conditions. HIV proteins consist of three types: regulatory proteins, accessory proteins, and structural proteins, which contribute to HIV-mediated bone loss partly by upregulating NF-κB expression, tumor necrosis factor alpha content, and release of inflammatory cytokines. Even worse, although antiretrovi-ral therapy has reduced HIV infection mortality and successfully transformed acquired immunodeficiency syndrome into a chronic disease, its impact on bone loss should not be overlooked, especially when the drug contains tenofovir. This review analyzes some reports focusing on the overall osteolytic situation due to imbalances in osteogenesis and bone resorption due to HIV infection and antiviral therapy. The intrinsic mechanism of bone loss provides a reference for researchers to analyze the risk factors for HIV patients complicated with bone loss and helps clinicians to provide ideas for the intervention and prevention of bone loss during clinical treatment and chronic disease management of HIV patients. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is the most prevalent cancer worldwide and accounts for approximately 20% of cancer-related death in China every year. High-grade lung cancer poses a significant threat to patients, and developing a novel treatment for these patients requires an understanding of its underlying mechanism. Methods: Chinese patients with lung cancer were enrolled. The tumor samples were collected by surgery or puncture and applied for next-generation sequencing. A panel of pan-cancer genes was targeted, and the sequencing depth was set to over 1,000 to improve the sensitivity of detecting mutations. Short-length mutations (substitution, insertion, and deletion), copy number variation, and gene fusion were called. Gene mutations were compared between low-grade, middle-grade, and high-grade tumors using Fisher's exact test. The enriched pathways in each grade of tumors were also inferred. Results: The study included 173 Chinese patients with non-small cell lung cancer, of whom 98 (56.6%) patients were female and 75 (43.4%) were male, with a mean age of 56.8 years. All patients were microsatellite stable; 66.4% were at the early stages (Stages 0, I, and II) with a tumor mutational burden of approximately 2.5 (confidence interval = [0, 48.3]). Compared to low-grade tumors, high-grade tumors had a significantly higher percentage of mutations in TP53 (75.9% vs 34.4%, p = 1.86e-3) and PIK3CA (24.1% vs. 0%, p = 3.58e-3). Pathway analysis found that high-grade tumors were enriched with mutations in bacterial invasion of epithelial cells (31% vs. 0%, p = 5.8e-4), Epstein-Barr virus infection (79.3% vs. 37.5%, p = 1.72e-3), and the Wnt signaling pathway (75.9% vs. 34.4%, p = 1.91e-3). High-grade tumors had a significantly higher tumor mutational burden than low-grade tumors (p-value = 0.0017). However, actionable mutations with high-level evidence were lower in high-grade tumors. Conclusion: Patients with high-grade tumors from lung cancer may be more affected by bacteria and Epstein-Barr virus than low-grade tumors. High-grade tumors were specially mutated in TP53 and PIK3CA and may benefit more from immunotherapy. Further research on the underlying mechanism of high-grade lung cancer is necessary to develop new therapeutic options. Lung cancer, tumor grade, genomic mutations, Epstein-Barr virus, pathway analysis. [ABSTRACT FROM AUTHOR]

Tomato disease is an important disease affecting agricultural production, and the combined infection of tomato chlorosis virus (ToCV) and tomato yellow leaf curl virus (TYLCV) has gradually expanded in recent years, but no effective control method has been developed to date. Both viruses are transmitted by Bemisia tabaci Mediteranean (MED). Previously, we found that after B. tabaci MED was fed on ToCV-and TYLCV-infected plants, the transmission efficiency of ToCV was significantly higher than that on plants infected only with ToCV. Therefore, we hypothesize that co-infection could enhance the transmission rates of the virus. In this study, transcriptome sequencing was performed to compare the changes of related transcription factors in B. tabaci MED co-infected with ToCV and TYLCV and infected only with ToCV. Hence, transmission experiments were carried out using B. tabaci MED to clarify the role of cathepsin in virus transmission. The gene expression level and enzyme activity of cathepsin B (Cath B) in B. tabaci MED co-infected with ToCV and TYLCV increased compared with those under ToCV infection alone. After the decrease in cathepsin activity in B. tabaci MED or cathepsin B was silenced, its ability to acquire and transmit ToCV was significantly reduced. We verified the hypothesis that the relative expression of cathepsin B was reduced, which helped reduce ToCV transmission by B. tabaci MED. Therefore, it was speculated that cathepsin has profound research significance in the control of B. tabaci MED and the spread of viral diseases. [ABSTRACT FROM AUTHOR]

The stable operation of power transmission and distribution is closely related to the overall performance and construction quality of circuit breakers. Focusing on circuit breakers as the research subject, we propose a machine vision method for automated defect detection, which can be applied in intelligent robots to improve detection efficiency, reduce costs, and address the issues related to performance and assembly quality. Based on the LeNet-5 convolutional neural network, a method for the detection of character defects on labels is proposed. This method is then combined with squeezing and excitation networks to achieve more precise classification with a feature graph mechanism. The experimental results show the accuracy of the LeNet-CB model can reach up to 99.75%, while the average time for single character detection is 17.9 milliseconds. Although the LeNet-SE model demonstrates certain limitations in handling some easily confused characters, it maintains an average accuracy of 98.95%. Through further optimization, a label content detection method based on the LSTM framework is constructed, with an average accuracy of 99.57%, and an average detection time of 84 milliseconds. Overall, the system meets the detection accuracy requirements and delivers a rapid response. making the results of this research a meaningful contribution to the practical foundation for ongoing improvements in robot intelligence and machine vision. [ABSTRACT FROM AUTHOR]

Objective: Lumbar cistern blockage is a common complication of continuous lumbar cistern drainage. This paper analyzes the risk factors for lumbar cistern blockage drainage due to various causes and proposes a series of prevention and intervention measures to reduce blockage or improve recanalization after blockage. Methods: The clinical data of 637 patients with various lesions who underwent lumbar cistern drainage in our hospital were retrospectively collected and analyzed. Perioperative clinical and imaging data were assessed. Variates were analyzed using univariate and multivariate logistic regression analyses. Results: A total of 13.7% (87/637) of patients had lumbar cistern blockage. Multivariate analysis revealed that drainage time (≥7 days), CSF volume <200 (mL/d), CSF leakage, and abnormal CSF properties were predictors of lumbar cistern blockage. Reducing the probability of lumbar cistern blockage can be achieved by repeatedly flushing, increasing the drainage flow and shortening the drainage time. The recanalization rate after blockage was 67.8% (59/87). After the drainage tube was removed, no complications related to the drainage tube occurred during the 1-week follow-up. Conclusion: Lumbar cistern blockage is the main reason for poor drainage. Prevention or early intervention can effectively reduce the probability of blockage and achieve the purpose of drainage of cerebrospinal fluid. [ABSTRACT FROM AUTHOR]

The first mitotic division of the initial cell is a key event in all multicellular organisms and is associated with the establishment of major developmental axes and cell fates. The brown alga Ectocarpus has a haploid-diploid life cycle that involves the development of two multicellular generations: the sporophyte and the gametophyte. Each generation deploys a distinct developmental programme autonomously from an initial cell, the first cell division of which sets up the future body pattern. Here, we show that mutations in the BASELESS (BAS) gene result in multiple cellular defects during the first cell division and subsequent failure to produce basal structures during both generations. BAS encodes a type B? regulatory subunit of protein phosphatase 2A (PP2A), and transcriptomic analysis identified potential effector genes that may be involved in determining basal cell fate. The bas mutant phenotype is very similar to that observed in distag (dis) mutants, which lack a functional Tubulin-binding co-factor Cd1 (TBCCd1) protein, indicating that TBCCd1 and PP2A are two essential components of the cellular machinery that regulates the first cell division and mediates basal cell fate determination. [ABSTRACT FROM AUTHOR]

Cyclic GMP-AMP Synthase (cGAS) is a pivotal adaptor of the signaling pathways involving the pattern recognition receptors and plays an important role in apoptosis and immune regulation. The cGAS function in mammals has been investigated extensively; however, the function of duck cGAS (du-cGAS) in response to viral infections is still unclear. This study aimed to clone the mallard (Anas platyrhynchos) cGAS homolog to investigate the function of duck cGAS (ducGAS) in host antiviral innate immunity. The results showed that the open reading frame (ORF) region of the du-cGAS gene was 1296 bp, encoding 432 amino acids (aa) and exhibiting similar functional domains with its chicken counterpart. Knockdown of the endogenous du-cGAS by specific sgRNA strongly increased the replication of DNA viruses, including duck adenovirus B2 (DAdV B2) and duck short beak and dwarfism syndrome virus (SBDSV). However, the knockout did not impair the replication of novel duck reovirus (NDRV), an RNA virus. Furthermore, the mRNA expressions of type I interferon (IFNs) and vital interferon-stimulated genes (ISGs) were remarkably reduced in the du-cGAS knockout DEF cell line. Inversely, du-cGAS overexpression greatly activated the transcription of IFN-a, IFN-β, and vital ISGs, and impaired the replication of DAdV B2, SBDSV, and NDRV in the DEF cell line. Importantly, we found that a deletion of 68 aa in the N terminus didn't impair the antiviral function of du-cGAS. Overexpressing NTase Core, CDomain (Mab21), or Zinc-Ribbon domain independently had no antiviral effects. Generally, these results reveal that du-cGAS is a vital component of the innate immune system of ducks, with a universal antiviral activity, and provides a useful strategy for the control of waterfowl viral diseases. [ABSTRACT FROM AUTHOR]

Background: This multicenter phase 1b/2 trial aimed to explore the maximum toler- ated dose (MTD), activity, and safety of anlotinib plus chemotherapy in patients with T790M-negative epidermal growth factor receptor (EGFR)-mutant advanced non- squamous non-small cell lung cancer (NSCLC) after resistance to first- or second- generation EGFR tyrosine kinase inhibitors (TKIs). Methods: In the phase 1b stage, patients received anlotinib (8/10/12 mg, days 1--14) combined with cisplatin (75 mg/m2, day 1) or carboplatin (AUC = 5, day 1) plus peme- trexed (500 mg/m2, day 1) for a 3-week cycle based on a 3 + 3 dose-escalation design. In the phase 2 single-arm stage, anlotinib was administered at MTD combined with plati- num plus pemetrexed for four cycles, followed by anlotinib maintenance therapy. The primary endpoint of the phase 2 stage was progression-free survival (PFS). Results: The study was prematurely terminated due to slow accrual after 19 patients had been enrolled between January 18, 2019, and March 21, 2021. The MTD of anloti- nib was 12 mg. The median PFS was 5.75 (95% confidence interval, 4.37--7.52) months. The objective response rate was 47.4% (95% confidence interval, 24.5%-- 71.1%). In the 12 mg group, seven (58.3%) patients experienced grade 3--4 treatment- related adverse events, and the most common ones were hypertension (6 [50.0%]), decreased platelet count (2 [16.7%]), and hypertriglyceridemia (1 [8.3%]). No treatment-related deaths occurred. Conclusion: Anlotinib plus platinum and pemetrexed showed promising antitumor activity with manageable toxicity in patients with T790M-negative EGFR-mutant advanced nonsquamous NSCLC after progression on first- or second-generation EGFR TKIs. [ABSTRACT FROM AUTHOR]

As a group of chronic and idiopathic gastrointestinal (GI) disorders, inflammatory bowel disease (IBD) is characterized by recurrent intestinal mucosal inflammation. Oral administration is critical for the treatment of IBD. Unfortunately, it is difficult to target the bowel located in the GI tract due to multiple physical barriers. The unique physicochemical properties of nanoparticle-based drug delivery systems (DDSs) and their enhanced permeability and retention effects in the inflamed bowel, render nanomedicines to be used to implement precise drug delivery at diseased sites in IBD therapy. In this review, we described the pathophysiological features of IBD, and designed strategies to exploit these features for intestinal targeting. In addition, we introduced the types of currently developed nano-targeted carriers, including synthetic nanoparticle-based and emerging naturally derived nanoparticles (e.g., extracellular vesicles and plant-derived nanoparticles). Moreover, recent developments in targeted oral nanoparticles for IBD therapy were also highlighted. Finally, we presented challenges associated with nanotechnology and potential directions for future IBD treatment. [ABSTRACT FROM AUTHOR]

Background: TNF-α inhibitors are effective biological agents for treating psoriasis, but the treatment responses differ across patients. This study aimed to identify genetic biomarkers of anti-TNF-α response in Chinese psoriasis patients using a genome-wide association approach.Methods: We recruited two independent cohorts of Chinese psoriasis patients administered etanercept biosimilar (with or without methotrexate). We identified 61 and 87 good responders (PASI improvement ≥75%), 19 and 10 poor responders (PASI improvement <50%) after 24 weeks treatment in the two cohorts, respectively. Then we performed genome-wide association studies (GWAS) on anti-TNF-α response in each cohort independently, followed by a fixed-effects inverse-variance meta-analysis in the 148 good and 29 poor responders.Results: We tested genetic associations with >3 million genetic variants in either cohort. Meta-analysis identified significant associations within seven loci at p < 10−5, which also showed consistent association evidence in the two cohorts. These seven loci include rs2431355 (OR = 6.65, p = 4.46 × 10−7, IQGAP2-F2RL2 on 5q13.3), rs11801616 (OR = 0.11, p = 1.75 × 10−6, SDC3 on 1p35.2), rs3754679 (OR = 0.17, p = 7.71 × 10−6, CNOT11 on 2q11.2), rs13166823 (OR = 0.09, p = 3.71 × 10−6, IRF1-AS1 on 5q31.1), rs10220768 (OR = 5.49, p = 1.48 × 10−6, NPAP1 on 15q11.2), rs4796752 (OR = 5.56, p = 1.49 × 10−6, KRT31 on 17q21.2), and rs13045590 (OR = 0.08, p = 9.67 × 10−7, CTSZ on 20q13.3). Of the seven SNPs, six SNPs showed significant eQTL effect (p < 1 × 10−6) for several genes in multiple tissues.Conclusion: These results suggest novel biological mechanisms and potential biomarkers for the response to anti-TNF therapies. These findings warrant further validation. [ABSTRACT FROM AUTHOR]

To achieve energy-efficient shortcut nitrogen removal of wastewater in the future, selective elimination of nitrite-oxidizing bacteria (NOB) while enriching ammonia-oxidizing microorganisms is a crucial step. However, the underlying mechanisms of partial nitrification are still not well understood, especially the newly discovered ultrasound-based partial nitrification. To elucidate this issue, in this study two bioreactors were set up, with one established partial nitrification by ultrasonication while the other didn't. During the operation of both reactors, the taxonomic and functional composition of the microbial community were investigated through metagenomics analysis. The result showed that during ultrasonic partial nitrification, ammonia-oxidizing archaea (AOA), Nitrososphaerales, was enriched more than ammonia-oxidizing bacteria (AOB), Nitrosomonas. The enrichment of microorganisms in the community increased the abundance of genes involved in microbial energy generation from lipid and carbohydrates. On the other hand, the abundance of NOB, Nitrospira and Nitrolancea, and Comammox Nitrospira decreased. Selective inhibition of NOB was highly correlated with genes involved in signal transduction enzymes, such as encoding histidine kinase and serine/threonine kinase. These findings provided deep insight into partial nitrification and contributed to the development of shortcut nitrification in wastewater treatment plants. [ABSTRACT FROM AUTHOR]

To overcome the challenges of the low efficiency of artemisinin (ART) in anticancer therapy due to its poor water solubility and poor bioavailability, we constructed folate (FA)-modified erythrocyte membrane (EM)camouflaged poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) (PFH/ ART@PLGA/Fe3O4-eFA). Specifically, the inner core of these NPs is mainly composed of phase-changeable perfluorohexane (PFH), magnetic Fe3O4 and ART. In vitro experiments showed that the prepared PFH/ART@PLGA/Fe3O4eFA was readily taken up by 4T1 cancer cells. PFH/ART@PLGA/Fe3O4-eFA was exposed to low-intensity focused ultrasound (LIFU) irradiation to induce PFH phase transition and NPs collapse, which promoted the release of ART and Fe3O4. After LIFU irradiation, the proportion of dead 4T1 cells, the level of reactive oxygen species (ROS) and the concentration of intracellular Fe2+ ions in the PFH/ART@PLGA/Fe3O4-eFA group were much higher than those in the other group, indicating that the synergistic effect between the intracellular Fe2+ ions and the released ART played a critical role in tumor cell ferroptosis by enhancing ROSgenerationinvitro. Wedemonstrated thatFA-modifiedEMNPs could enhance the targeting and accumulation of the NPs at the tumor site in vivo. After LIFU irradiation at 3 W/m² for 7 min, tumor growth was completely suppressed through FA-modified EM NPs collapse and the release of ART and Fe3O4, whichexerted synergistic effects in inducing tumor ferroptosis. Because of these characteristics, these NPs are considered as a promising approach for the delivery of drugs with poor water solubility for efficient cancer therapy. [ABSTRACT FROM AUTHOR]

Objective: Long-term acupoint stimulation (LAS), also called embedding acupuncture, is a modified acupuncture technique. The preliminary results have demonstrated its efficacy in body-weight control. However, the low quality of available trials limited its application. This study aimed to evaluate the efficacy and safety of LAS in body-weight control by using a randomized, parallel, sham-controlled clinical trial design. Methods: This was a randomized, single-blind, sham-controlled clinical trial including 84 adult participants (18-60 years) with a body mass index (BMI) of = 24 kg/m² conducted in three general hospitals in Shanghai, China. Participants were equally assigned to receive LAS or sham LAS (SLAS) once per 10 days, eight times in total. After completion, an additional intervention with a 3-month follow-up period was set to examine the continued effect of LAS. The primary outcome was the change in body weight from baseline to treatment endpoint within the intention-to-treat (ITT) analysis. Secondary outcomes contained changes in waist-to-hip ratio (WHR), lipid metabolism, and visceral and subcutaneous adipose tissues. Results: From 14 May 2018 to 03 November 2019, 84 participants out of 201 screened individuals met the eligibility criteria, were randomized, and were analyzed (42 participants in each group). From baseline to treatment endpoint, the body-weight reduction in the LAS group was significantly larger than in the sham control (net difference: 1.57 kg, 95% CI: 0.29-2.86, p = 0.012). The superior weight reduction effect persisted in the follow-up period (net difference: 3.20 kg, 95% CI: 1.17-5.21, p = 0.001). LAS therapy also showed improvement in triglyceride and subcutaneous adipose tissue (SAT) compared with sham control. One participant in the LAS group reported a slightly uncomfortable and tingling sensation after the additional intervention. No other adverse events (AEs) were documented. Conclusion: LAS, a modified acupuncture technique, is safe and effective in body-weight control. It could be used as an alternative choice to classical acupuncture for obesity management. [ABSTRACT FROM AUTHOR]

To achieve energy-efficient shortcut nitrogen removal of wastewater in the future, selective elimination of nitrite-oxidizing bacteria (NOB) while enriching ammoniaoxidizing microorganisms is a crucial step. However, the underlying mechanisms of partial nitrification are still not well understood, especially the newly discovered ultrasound-based partial nitrification. To elucidate this issue, in this study two bioreactors were set up, with one established partial nitrification by ultrasonication while the other didn't. During the operation of both reactors, the taxonomic and functional composition of the microbial community were investigated through metagenomics analysis. The result showed that during ultrasonic partial nitrification, ammonia-oxidizing archaea (AOA), Nitrososphaerales, was enriched more than ammonia-oxidizing bacteria (AOB), Nitrosomonas. The enrichment of microorganisms in the community increased the abundance of genes involved in microbial energy generation from lipid and carbohydrates. On the other hand, the abundance of NOB, Nitrospira and Nitrolancea, and Comammox Nitrospira decreased. Selective inhibition of NOB was highly correlated with genes involved in signal transduction enzymes, such as encoding histidine kinase and serine/threonine kinase. These findings provided deep insight into partial nitrification and contributed to the development of shortcut nitrification in wastewater treatment plants. [ABSTRACT FROM AUTHOR]

Swab samples were collected from 34 pangolins in Guangxi Province, China. Metavirome sequencing and bioinformatics approaches were undertaken to determine the abundant viral sequences in the viromes. The results showed that the viral sequences belong to 24 virus taxonomic families. To verify the results, PCR combined with phylogenetic analysis was conducted. Some viral sequences including Japanese encephalitis virus (JEV), Getah virus (GETV), and chikungunya virus (CHIKV) were detected. On the basis of the metavirome analysis, seven segments belonging to JEV were further identified through PCR amplification. Sequence comparison showed that, among seven sequences, JEVChina/P2020E-1 displayed the highest nucleotide (80.6%), with the JEV isolated in South Korea, 1988, and all of which belonging to genotype III. Seven CHIKV sequences were detected, with the highest homology (80.6%) to the Aedes africanus in CoÌ, te d'Ivoire, 1993. Moreover, passage from BHK-21 to Vero cells makes the newly isolated CHIKVChina/P2020-1 more contagious. In addition, the newly verified GETV sequences shared 86.4% identity with the 1955 GETV isolated from Malaysia. Some sudden and recurrent viruses have also been observed from the virome of pangolin in Guangxi Province, China; hence, dissemination tests will be implemented in the future. [ABSTRACT FROM AUTHOR]

Plant and fruit surfaces are covered with cuticle wax and provide a protective barrier against biotic and abiotic stresses. Cuticle wax consists of very-long-chain fatty acids (VLCFAs) and their derivatives. β-Ketoacyl-CoA synthase (KCS) is a key enzyme in the synthesis of VLCFAs and provides a precursor for the synthesis of cuticle wax, but the KCS gene family was yet to be reported in the passion fruit (Passiflora edulis). In this study, thirty-two KCS genes were identified in the passion fruit genome and phylogenetically grouped as KCS1 -like, FAE1 -like, FDH -like, and CER6 -like. Furthermore, thirty-one PeKCS genes were positioned on seven chromosomes, while one PeKCS was localized to the unassembled genomic scaffold. The cis -element analysis provides insight into the possible role of PeKCS genes in phytohormones and stress responses. Syntenic analysis revealed that gene duplication played a crucial role in the expansion of the PeKCS gene family and underwent a strong purifying selection. All PeKCS proteins shared similar 3D structures, and a protein–protein interaction network was predicted with known Arabidopsis proteins. There were twenty putative ped-miRNAs which were also predicted that belong to nine families targeting thirteen PeKCS genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation results were highly associated with fatty acid synthase and elongase activity, lipid metabolism, stress responses, and plant-pathogen interaction. The highly enriched transcription factors (TFs) including ERF, MYB, Dof, C2H2, TCP, LBD, NAC, and bHLH were predicted in PeKCS genes. qRT-PCR expression analysis revealed that most PeKCS genes were highly upregulated in leaves including PeKCS2, PeKCS4, PeKCS8, PeKCS13 , and PeKCS9 but not in stem and roots tissues under drought stress conditions compared with controls. Notably, most PeKCS genes were upregulated at 9th dpi under Fusarium kyushuense biotic stress condition compared to controls. This study provides a basis for further understanding the functions of KCS genes, improving wax and VLCFA biosynthesis, and improvement of passion fruit resistance. [ABSTRACT FROM AUTHOR]

Although lithium--sulfur (Li--S) batteries possess great potential to become the next generation of energy storage technology due to their fivefold higher energy density than commercial lithium-ion batteries, their practical application is still hindered by their poor cycling stability, especially resulting from the disturbing shuttle effect of soluble intermediates. In this study, vanadium dioxide (VO2) nanosheets were successfully grown onto CNTs to form CNTs@VO2 through hydrothermal and calcining processes. The hollow structure of the high conductive CNTs offers internal space and mesopores to accommodate the electrolyte combined with the polar metal oxide VO2 nanosheets providing the chemical anchoring. The hollow binary core--shell host acting as the nanoreactor that serves as the modifier of the separator results in the intensive physical and chemical dual adsorption of lithium polysulfide species (LiPSs), promoting the conversion of long-chain LiPSs to alleviate the shuttle effect significantly and boosting the performance. In addition, the CNTs enhance the electronic conductivity and the electrolyte infiltration of the separator. Notably, the modified separator demonstrates a high initial discharge capacity of 1397 mA h g-1 at 0.2C and retains a stable cycling ability with a reversible capacity of 965 mA h g-1 over 200 cycles at 1C. Even for the high sulfur loading of 7.4 mg cm-2, it can deliver a high areal capacity of 5.4 mA h cm-2 at 0.5C. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible coronavirus responsible for the global COVID-19 pandemic. Herein, we provide evidence that SARS-CoV-2 spreads through cell-cell contact in cultures, mediated by the spike glycoprotein. SARS-CoV-2 spike is more efficient in facilitating cellto-cell transmission than is SARS-CoV spike, which reflects, in part, their differential cell-cell fusion activity. Interestingly, treatment of cocultured cells with endosomal entry inhibitors impairs cell-to-cell transmission, implicating endosomal membrane fusion as an underlying mechanism. Compared with cell-free infection, cell-to-cell transmission of SARS-CoV-2 is refractory to inhibition by neutralizing antibody or convalescent sera of COVID-19 patients. While angiotensin-converting enzyme 2 enhances cell-to-cell transmission, we find that it is not absolutely required. Notably, despite differences in cell-free infectivity, the authentic variants of concern (VOCs) B.1.1.7 (alpha) and B.1.351 (beta) have similar cell-to-cell transmission capability. Moreover, B.1.351 is more resistant to neutralization by vaccinee sera in cell-free infection, whereas B.1.1.7 is more resistant to inhibition by vaccinee sera in cell-to-cell transmission. Overall, our study reveals critical features of SARS-CoV-2 spikemediated cell-to-cell transmission, with important implications for a better understanding of SARS-CoV-2 spread and pathogenesis. [ABSTRACT FROM AUTHOR]