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Background: The causal associations and potential mechanisms between prostatic diseases, the predominant male urological disorders, and the course of COVID-19 remain unclear. Methods: A two-sample Mendelian randomization (MR) analysis was performed to evaluate causal associations between prostate cancer, benign prostatic hyperplasia, and prostatitis and different COVID-19 outcomes (SARS-CoV-2 infection, hospitalized COVID-19, and severe COVID-19). Reverse MR, linkage disequilibrium score regression, and Bayesian colocalization analyses were subsequently performed to strengthen the identified causal relationships. Furthermore, immunome- and metabolome-wide MR analysis was conducted to prioritize COVID-19-associated immune characteristics and metabolites. Two-step MR analysis was performed to evaluate the mediating effects of the immunome and metabolome on the associations between prostatic diseases and COVID-19. Results: Genetically predicted prostatic diseases were not causally associated with severe COVID-19, while prostatitis was suggested to be an independent risk factor for SARS-CoV-2 infection (odds ratio (OR) = 1.11, 95% confidence interval (CI) 1.01 to 1.23; P = 0.03). Multiple sensitivity tests verified the reliability of the established causal relationships. Dozens of blood immune and metabolic features were identified to reveal the immune and metabolic profiles of different COVID-19 courses. Moreover, PDL-1 on monocyte was found to mediate the interaction between prostatitis and SARS-CoV-2 infection, with a mediation proportion of 9.2%. Conclusion: Our study identified the causal relationships of prostatic diseases with COVID-19 and suggested pathways explaining these associations through alterations in the blood immunome and metabolome.

Abstract A large amount of heat accumulates in the engine bay for a short time after the engine runs at high load and shuts down, that will lead to thermal damage and thermal fatigue caused by the temperature rise of some heat sensitive components. This paper uses an aero-thermal coupling approach to study the heat transfer problem in the engine bay of an SUV model under thermal soak conditions. Due to the transient characteristics of the heat transfer process, the natural transient CFD software developed based on the LBM method is used to study the engine bay heat transfer during the 400 s key-off soak process. The analysis reveals that convection and radiation are the main heat transfer modes in the early stage of hot immersion (0–120 s), and conduction only makes a significant contribution in contact with high temperature sources. The radiation and convection are the key contributors to heat transfer processes of engine bay during soak, but the efficiency of radiation heat transfer decreases with the increase of time, whereas the efficiency of convection heat transfer is not always reduced, it will increase and then decrease with the increase of time. The coupling method established can predict the thermal state in the engine bay well, and is in good agreement with the experimental results. The results show that the error in the engine coolant temperature is less than 1 °C, and the error in the temperature of the heat-sensitive components is less than 5 °C. Finally, the potential risks of thermal damage and thermal fatigue states were assessed, providing an important reference for the control design of cooling fan running time after key-off.

Cassia Semen, derived from the dried ripe seeds of leguminous plant Cassia obtusifolia Linn. or Cassia. tora Linn., exhibits a variety of pharmacological effects such as clearing heat to brighten the eyes, lubricating the intestine to relieve constipation, lowering blood pressure and lipids, hepatoprotection and anti-diabetes, etc. And due to its homology of medicine and food, it has broad development prospects in the fields of medicine and food. Based on the summary and analysis of the published literatures, this paper systematically reviews the integrated research progress of Cassiae Semen in recent years from the aspects of bioactive ingredients, pharmacological effects, toxicity and its applications in the food field. Additionally, the emerging challenges and possible development directions for the study of Cassiae Semen are discussed as well. In future research on Cassiae Semen, more attention should be paid to the pharmacological effects of naphthopyranones and polysaccharides and their mechanisms underlying improving eye diseases. Meanwhile, it is essential to focus on strengthening the researches on the pharmacokinetics of Cassiae Semen and the safety evaluation of its related functional foods. This article provides new basic information for further research, development, and utilization of Cassiae Semen.

Abstract Ovalbumin (OVA) in egg is one of the predominant causes of food allergy around the world. In the present study, the alleviating effect of selenium‐enriched tea polysaccharide (Se‐TPS) on OVA allergy was evaluated, and the underlying mechanistic insights were investigated. Se‐TPS significantly alleviated the clinical manifestations and diarrhea of allergic mice, accelerated the recovery of jejunal injury, and decreased the immune organ index. Meanwhile, Se‐TPS decreased the levels of immunoglobulin E (IgE), histamine, and IL‐4 in serum, increased the levels of IFN‐γ, and promoted the balance of Th1/Th2 cells. Furthermore, the intervention of Se‐TPS reshaped the gut microbiota structure of OVA‐allergic mice. Se‐TPS increased the abundance of Lachnospiraceae_NK4A136_group, unclassified_f_Lachnospiraceae, and Alistipes, whereas decreased the Faecalibaculum abundance. Analysis of intestinal metabolites showed that Se‐TPS treatment caused a significant increase in homocitrulline and 7a‐hydroxyandrost‐4‐ene‐3,17‐dione levels. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment results indicated that Se‐TPS treatment may alleviate allergic symptoms by enhancing the anti‐inflammatory ability of OVA‐allergic mice through neuroimmunity.

Abstract Prostate cancer (PCa) is the most common cancer among men in the United States and the leading cause of cancer-related death. The Solute Carrier Family 14 Member 1 (SLC14A1) is a member of urea transporters which are important for the regulation of urine concentration. However, the physiological significance of SLC14A1 in PCa still remains unclear. In the present study, via bioinformatics analysis and experiments, we found that expression of SLC14A1 is significantly decreased in PCa progression, which could be attributed to hypermethylation on SLC14A1 promoter region. Moreover, its low expression and hypermethylation on SLC14A1 promoter are closely related to the poor prognosis of PCa patients. On the other hand, overexpression of SLC14A1 inhibited cell proliferation and metastasis while its overexpression also suppressed CDK1/CCNB1 pathway and mTOR/MMP-9 signaling pathway. Additionally, SLC14A1 expression is enriched in prostate basal-type cells. In summary, our study indicates that its low expression level and promoter hypermethylation of SLC14A1 may represent novel indicators for PCa progression and prognosis, and SLC14A1 could inhibit the progression of PCa.

Abstract Accurate cropland map serves as the cornerstone of effective agricultural monitoring. Despite the continuous enrichment of remotely sensed cropland maps, pervasive inconsistencies have impeded their further application. This issue is particularly evident in areas with limited valid observations, such as southwestern China, which is characterized by its complex topography and fragmented parcels. In this study, we constructed multi-sourced samples independent of the data producers, taking advantage of open-source validation datasets and sampling to rectify the accuracy of ten contemporary cropland maps in southwestern China, decoded their inconsistencies, and generated a refined cropland map (CroplandSyn) by leveraging ten state-of-the-art remotely sensed cropland maps released from 2021 onwards using the self-adaptive threshold method. Validations, conducted at both prefecture and county scales, underscored the superiority of the refined cropland map, aligning more closely with national land survey data. The refined cropland map and samples are publicly available to users. Our study offers valuable insights for improving agricultural practices and land management in under-monitored areas by providing high-quality cropland maps and validation datasets.

Abstract Objective This study was performed to explore the differences in the clinical characteristics and oxidative stress indicators, inflammatory factors, and pathological proteins in serum between Parkinson’s disease (PD) with anxiety (PD-A) and with no anxiety (PD-NA) patients, and further correlations among clinical characteristics and above variables were analyzed in PD-A and PD-NA groups. Methods A total of 121 patients with PD were enrolled in this study and assessed by the Hamilton Anxiety Scale (14 items) (HAMA-14). These patients were divided into PD-A and PD-NA groups according to a cut-off point of 7 of HAMA-14. Demographic variables were collected, and clinical symptoms were assessed by multiple rating scales. The levels of free radicals, inflammatory factors, and pathological proteins in serum were measured by chemical colorimetric method and enzyme-linked immunosorbent assay (ELISA). The differences of above variables were compared between PD-A and PD-NA groups, and the correlations of clinical symptoms with the abovevariables were analyzed in PD-A and PD-NA groups. Results The frequency of PD-A was 62.81%. PD-A group exhibited significantly impaired motor dysfunction and multiple non-motor symptoms, including fatigue, sleep behavior disorder, restless leg syndrome and autonomic dysfunction, and dramatically compromised activities of daily living compard with PD-NA group. PD-A group displayed prominently increasedlevels of hydroxyl radical (·OH) and tumor necrosis factor (TNF)-α, and a decreased nitric oxide (NO) level in serum compared with PD-NA group (P

Amorphous carbon coatings by various physical vapor deposition (PVD) have been widely attempted for enhancing both anti-wear and corrosion resistance of bulk materials used in harsh marine environments. However, PVD coatings are apt to be worn due to the existence of growth defects mostly like macro-size nodular particles. In this work, we deliberately fabricated the SiO2 nanoparticles with a size of 200 nm as nodular defects in Cr and graphite-like carbon (Cr/GLC) multilayer coatings, and the dependence of tribocorrosion behavior of coating on the nodular defects was focused by the comprehensively tribological and electrochemical tests. The results showed that introducing SiO2 nodular particles could not degrade the mechanical properties of Cr/GLC coating, but significantly accelerated both the abrasive wear in early sliding-stage under dry friction and the corrosive failure in chloride solution. Particularly, once the tribocorrosion tests in 3.5 wt.% NaCl solution were conducted for the Cr/GLC coating with nodular defects, the distinct ploughing damage originated from abrasive wear promoted the localized spallation of coatings, which thereafter enabled the easy water wedging along spallation for the substantial catastrophe of coatings. The present observations could evident the importance to fabricate the defect-free protective coatings required for harsh tribocorrosion applications.

Lycodon gammiei (Blanford, 1878), a rarely encountered species of Asian snake, is characterized by ambiguous systematics and biology. Based on a sole specimen of L. gammiei rediscovered in southeastern Xizang, China, we conduct a detailed morphological examination and description, and investigate the systematic position of this species. Morphologically, the newly collected specimen is closely aligned with specimens previously described. Mitochondrial DNA-based phylogenetic analyses reveal that L. gammiei constitutes an independent evolutionary lineage, forming a clade with L. fasciatus (Anderson, 1879), L. gongshan Vogel & Luo, 2011, L. butleri Boulenger, 1900, and L. cavernicolus Grismer, Quah, Anuar, Muin, Wood & Nor, 2014. The closest genetic distance between L. gammiei and its congeners was 10.2%. The discovery of L. gammiei in Medog County, China, signifies an eastward expansion of its known geographical distribution.

Abstract The corrosion failure of amorphous carbon (a-C) coatings is commonly ascribed to the existence of growth microdefects, which serve as pathways for corrosive fluids to permeate the substrate. Atomic layer deposition (ALD) is renowned for its ability to augment the corrosion resistance of metallic materials. Graphite-like carbon (GLC) is one of the amorphous carbon materials dominated by hybridized sp2-C bonds. In this study, an ALD-deposited Al2O3 layer is specially introduced on the Cr/GLC multilayer coating to solve the aforementioned corrosion risk of a-C by taking the sealing conception for defects. Compared to the as-deposited Cr/GLC coating, the coating encapsulated with Al2O3 layer depicts the reduction of corrosion current density over two orders of magnitude under a wide pressure range of 0.1 ~ 15 MPa. Particularly, the presence of released Crn+ and Fen+ in the corrosion solution is significantly diminished, accompanying with a small quantity of Aln+ generated in sealed coating during corrosion. Microstructural analysis and electrochemical results identified that both the dense Al2O3 layer offered strong safeguard for Cr elements released from multilayers, whilst amorphous carbon network inhibited the likelihood chloride penetration induced by partially infiltrated Al2O3, which made the synergistic contributions to the enhancement of corrosion resistance for Cr/GLC coating for deep-sea applications.

Zein is widely used in loading and delivery of food functional components due to its unique self-assembly properties. However, due to the strong hydrophobicity, the interface stability of the pure Zein-based Pickering emulsion is difficult to meet the needs of practical applications, and the construction of a composite system with appropriate polysaccharides is an effective strategy to improve the stability of its emulsion. On account of this, composite particles (NZPs) using Zein and Nicandra physaloides gum (NPG) with different protein-polysaccharide compounding ratios were prepared in this work by complex coacervation method. The physicochemical properties, structure and emulsion properties of NZPs were characterized. The results showed that the surface wettability of NZPs increased with the increasing addition of NPG, and meanwhile the formed composite particles became smaller with better dispersity, caused by the specific electrostatic force between protein and polysaccharide. The endogenous fluorescence spectrum of NZPs showed that the peak intensity of the corresponding characteristic peaks was proportional to the content of Zein and NPG, respectively, and the introduction of NPG affected the microenvironment polarity of tyrosine residues in Zein molecules. The shift of the absorption peak in Fourier transform infrared spectroscopy (FT-IR) indicated the enhanced hydrogen bond interaction and the generation of new peaks indicated the formation of new chemical bonds in NZPs. The storage modulus (G') of NZPs-based Pickering emulsions was higher than the loss modulus (G"). When the compounding ratio was 1:1 (Zein:NPG), both G' and G" of emulsions reached the maximum, obtaining the optimum emulsion system structure. The creaming index (CI) results showed that the stability of NZPs-based Pickering emulsions was generally higher than that of the pure Zein or NPG emulsions under different pH and heating treatments. This study provides a theoretical reference for the development of new Zein-polysaccharide composite system and its highly efficient and stable Pickering emulsions.

Immunotherapy represents a promising strategy for cancer treatment that utilizes immune cells or drugs to activate the patient’s own immune system and eliminate cancer cells. One of the most exciting advances within this field is the targeting of neoantigens, which are peptides derived from non-synonymous somatic mutations that are found exclusively within cancer cells and absent in normal cells. Although neoantigen-based therapeutic vaccines have not received approval for standard cancer treatment, early clinical trials have yielded encouraging outcomes as standalone monotherapy or when combined with checkpoint inhibitors. Progress made in high-throughput sequencing and bioinformatics have greatly facilitated the precise and efficient identification of neoantigens. Consequently, personalized neoantigen-based vaccines tailored to each patient have been developed that are capable of eliciting a robust and long-lasting immune response which effectively eliminates tumors and prevents recurrences. This review provides a concise overview consolidating the latest clinical advances in neoantigen-based therapeutic vaccines, and also discusses challenges and future perspectives for this innovative approach, particularly emphasizing the potential of neoantigen-based therapeutic vaccines to enhance clinical efficacy against advanced solid tumors.

Abstract Therapeutic benefits and underlying biomechanism(s) of antibody drug conjugates (ADC) in combination with other targeted therapeutics are largely unknown. Here, the synergy between ADC and epigenetic drug decitabine (DAC), a clinically approved DNA methylation inhibitor, in multiple preclinical models of melanoma specifically investigated. Mechanistically, the underlying biomechanisms of how DAC cooperatively worked with ICAM1 antibody conjugated DNA topoisomerase I inhibitor DXd (I1‐DXd) is elucidated. DAC treatment significantly enhanced anti‐tumor efficacy of I1‐DXd by upregulating antigen expression, enhancing antibody internalization and potentiating tumor sensitivity by epigenetically reprogramming of melanoma. Meanwhile, I1‐DXd/DAC combination also exerted regulatory effects on tumor microenvironment (TME) by enhancing tumor infiltration of innate and adaptive immune cells and improving penetration of ADCs with a boosted antitumor immunity. This study provides a rational ADC combination strategy for solid tumor treatment.

IntroductionThe cardiothoracic ratio (CTR) based on postero-anterior chest X-rays (P-A CXR) images is one of the most commonly used cardiac measurement methods and an indicator for initially evaluating cardiac diseases. However, the hearts are not readily observable on P-A CXR images compared to the lung fields. Therefore, radiologists often manually determine the CTR’s right and left heart border points of the adjacent left and right lung fields to the heart based on P-A CXR images. Meanwhile, manual CTR measurement based on the P-A CXR image requires experienced radiologists and is time-consuming and laborious.MethodsBased on the above, this article proposes a novel, fully automatic CTR calculation method based on lung fields abstracted from the P-A CXR images using convolutional neural networks (CNNs), overcoming the limitations to heart segmentation and avoiding errors in heart segmentation. First, the lung field mask images are abstracted from the P-A CXR images based on the pre-trained CNNs. Second, a novel localization method of the heart’s right and left border points is proposed based on the two-dimensional projection morphology of the lung field mask images using graphics.ResultsThe results show that the mean distance errors at the x-axis direction of the CTR’s four key points in the test sets T1 (21 × 512 × 512 static P-A CXR images) and T2 (13 × 512 × 512 dynamic P-A CXR images) based on various pre-trained CNNs are 4.1161 and 3.2116 pixels, respectively. In addition, the mean CTR errors on the test sets T1 and T2 based on four proposed models are 0.0208 and 0.0180, respectively.DiscussionOur proposed model achieves the equivalent performance of CTR calculation as the previous CardioNet model, overcomes heart segmentation, and takes less time. Therefore, our proposed method is practical and feasible and may become an effective tool for initially evaluating cardiac diseases.

Humic electron mediators can facilitate the reductive dehalogenation of organohalogenated compounds by accelerating electron transfer. To investigate the effect of humic electron mediators on the microbial anaerobic reductive dechlorination of Polychlorinated biphenyls (PCBs), three types of humic electron mediators, humin (HM), humic acid (HA), and anthraquinone-2,6-disulfonic acid (AQDS, HA analogs), were added to PCB dechlorination cultures enriched from different sources in terrestrial and marine environments (T and M cultures). The results showed that meta- and para-site dechlorination occurred in the M culture, while only meta-site dechlorination occurred in the T culture. The dechlorination process N and the dechlorination process H or H′ are presented in both cultures. HM enhanced PCB dechlorination metabolic activity in both cultures mainly by promoting meta-site dechlorination. HA showed a weak promoting effect on the M culture by promoting para-chlorine removal but inhibited the dechlorination metabolism of the terrestrial-origin culture, inhibiting meta-chlorine removal. AQDS showed inhibitory effects on both cultures by inhibiting the microbial removal of meta-chlorine. High-throughput sequencing and qPCR results suggest that HM is not a carbon source for the potential dechlorinating metabolism of Dehalococcoides but may promote reductive dechlorination by changing the community structure, and AQDS may inhibit anaerobic reductive dechlorination of PCBs by inhibiting the growth of Dehalococcoides. This study provides insights into the mechanism of enhancing PCB microbial dechlorination mediated by humic substances and plays a significant role in extending the application prospects of PCBs bioremediation technology.

Puerarin, a monomer of traditional Chinese medicine, is a key component of Pueraria radix. Both clinical and experimental researches demonstrated that puerarin has therapeutic effects on Parkinson's disease (PD). Puerarin's pharmacological mechanisms include: 1) Anti-apoptosis. Puerarin inhibits cell apoptosis through the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (Akt) and c-Jun N-terminal kinase (JNK) signaling pathways. Puerarin also exerts a hormone-like effect against cell apoptosis; 2) Anti-oxidative stress injury. Puerarin inhibits the Nrf2 nuclear exclusion through the GSK-3β/Fyn pathway to promote the Nrf2 accumulation in the nucleus, and then promotes the antioxidant synthesis through the Nrf2/ARE signaling pathway to protect against oxidative stress; 3) Neuroprotective effects by intervening in the ubiquitin-proteasome system (UPS) and autophagy-lysosomal pathway (ALP). Puerarin significantly enhances the activity of chaperone-mediated autophagy (CMA), which downregulates the expression of α-synuclein, reduces its accumulation, and thus improves the function of damaged neurons. Additionally, puerarin increases proteasome activity and decreases ubiquitin-binding proteins, thereby preventing toxic accumulation of intracellular proteins; 4) Alleviating inflammatory response. Puerarin inhibits the conversion of microglia to the M1 phenotype while inducing the transition of microglia to the M2 phenotype. Furthermore, puerarin promotes the secretion of anti-inflammatory factor and inhibits the expression of pro-inflammatory factors; 5) Increasing the levels of dopamine and its metabolites. Puerarin could increase the levels of dopamine, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum; 6) Promoting neurotrophic factor expression and neuronal repair. Puerarin increases the expression of glial cell-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), thereby exerting a neuroprotective effect. Moreover, the regulation of the gut microbiota by puerarin may be a potential mechanism for the treatment of PD. The current review discusses the molecular mechanisms of puerarin, which may provide insight into the active components of traditional Chinese medicine in the treatment of PD.

Information on vegetation dynamics is important for agricultural and ecological management. However, a systematic framework for the study of vegetation dynamics is still lacking. Therefore, this study developed the Vegetation Dynamic Change And Land Cover (VDCALC) framework to achieve a comprehensive analysis of vegetation dynamic change. The framework uses the Normalized Difference Vegetation Index (NDVI) data derived from the Moderate Resolution Imaging Spectroradiometer (MODIS) and Global Inventory Modeling and Mapping Studies (GIMMS), along with land cover data as input. It combines several models, including the Theil-Sen median, Mann-Kendall test and coefficient of variation, which can qualitatively and quantitatively study the spatiotemporal dynamic change of vegetation, and Hurst exponent model, which was used to predict the future change. Meteorological and statistical data were used as auxiliary data in this framework to analyze the influencing factors of vegetation change. Results showed that the degradation area was mainly concentrated in the coastal areas of the peninsula, Rizhao, Weifang, Linyi and Zibo during the period from 2001 to 2015, accounting for 36.05%. Based on annual-scale data, the NDVI showed an overall improvement trend, with significant increases in spring and autumn. However, predictions indicated that the degraded area would account for 37.18% in the future. In addition, meteorological factors were found to influence vegetation growth differently depending on the season. This study demonstrated a complete and reliable framework for effectively reflecting regional vegetation changes. It is recommended for application in large-scale areas to guide agricultural and ecological management.

Since the patients suffering from female lower genital tract diseases are getting younger and younger and the human papilloma virus (HPV) infection is becoming more widespread, the novel non-invasive precise modalities of diagnosis and therapy are required to remain structures of the organ and tissue, and fertility as well, by which the less damage to normal tissue and fewer adverse effects are able to be achieved. In all nucleated mammalian cells, 5-Aminolevulinic acid (5-ALA) is an amino acid that occurs spontaneously, which further synthesizes in the heme biosynthetic pathway into protoporphyrin IX (PpIX) as a porphyrin precursor and photosensitizing agent. Exogenous 5-ALA avoids the rate-limiting step in the process, causing PpIX buildup in tumor tissues. This tumor-selective PpIX distribution after 5-ALA application has been used successfully for tumor photodynamic diagnosis (PDD) and photodynamic therapy (PDT). Several ALA-based drugs have been used for ALA-PDD and ALA-PDT in treating many (pre)cancerous diseases, including the female lower genital tract diseases, yet the ALA-induced fluorescent theranostics is needed to be explored further. In this paper, we are going to review the studies of the mechanisms and applications mainly on ALA-mediated photodynamic reactions and its effectiveness in treating female lower genital tract diseases.

Abstract Steroid receptor coactivator-1 (SRC-1, also known as NCOA1) frequently functions as a transcriptional coactivator by directly binding to transcription factors and recruiting to the target gene promoters to promote gene transcription by increasing chromatin accessibility and promoting the formation of transcriptional complexes. In recent decades, various biological and pathological functions of SRC-1 have been reported, especially in the context of tumorigenesis. SRC-1 is a facilitator of the progression of multiple cancers, including breast cancer, prostate cancer, gastrointestinal cancer, neurological cancer, and female genital system cancer. The emerging multiorgan oncogenic role of SRC-1 is still being studied and may not be limited to only steroid hormone-producing tissues. Growing evidence suggests that SRC-1 promotes target gene expression by directly binding to transcription factors, which may constitute a novel coactivation pattern independent of AR or ER. In addition, the antitumour effect of pharmacological inhibition of SRC-1 with agents including various small molecules or naturally active compounds has been reported, but their practical application in clinical cancer therapy is very limited. For this review, we gathered typical evidence on the oncogenic role of SRC-1, highlighted its major collaborators and regulatory genes, and mapped the potential mechanisms by which SRC-1 promotes primary tumour progression.

Abstract Background CT examination for lung cancer has been carried out for more than 20 years and great achievements have been made in the early detection of lung cancer. However, in the clinical work, a large number of advanced central lung squamous cell carcinoma are still detected through bronchoscopy. Meanwhile, a part of CT-occult central lung squamous cell carcinoma and squamous epithelial precancerous lesions are also accidentally detected through bronchoscopy. Methods This study retrospectively collects the medical records of patients in the bronchoscopy room of the Endoscopy Department of Zhejiang Cancer Hospital from January 2014 to December 2018. The inclusion criteria for patients includes: 1.Patient medical records completed, 2.Without history of lung cancer before the diagnosis and first pathological diagnosis of primary lung cancer, 3.Have the lung CT data of the same period, 4.Have the bronchoscopy records and related pathological diagnosis, 5.The patients undergoing radical surgical treatment must have a complete postoperative pathological diagnosis. Finally, a total of 10,851 patients with primary lung cancer are included in the study, including 7175 males and 3676 females, aged 22–98 years. Firstly, 130 patients with CT-occult lesions are extracted and their clinical features are analyzed. Then, 604 cases of single central squamous cell carcinoma and 3569 cases of peripheral adenocarcinoma are extracted and compares in postoperative tumor diameter and lymph node metastasis. Results 115 cases of CT-occult central lung squamous cell carcinoma and 15 cases of squamous epithelial precancerous lesions are found. In the total lung cancer, the proportion of CT-occult lesions is 130/10,851 (1.20%). Meanwhile, all these patients are middle-aged and elderly men with a history of heavy smoking. There are statistically significant differences in postoperative median tumor diameter (3.65 cm vs.1.70 cm, P

Abstract Photocatalytic overall water splitting into hydrogen and oxygen is desirable for long-term renewable, sustainable and clean fuel production on earth. Metal sulfides are considered as ideal hydrogen-evolved photocatalysts, but their component homogeneity and typical sulfur instability cause an inert oxygen production, which remains a huge obstacle to overall water-splitting. Here, a distortion-evoked cation-site oxygen doping of ZnIn2S4 (D-O-ZIS) creates significant electronegativity differences between adjacent atomic sites, with S1 sites being electron-rich and S2 sites being electron-deficient in the local structure of S1–S2–O sites. The strong charge redistribution character activates stable oxygen reactions at S2 sites and avoids the common issue of sulfur instability in metal sulfide photocatalysis, while S1 sites favor the adsorption/desorption of hydrogen. Consequently, an overall water-splitting reaction has been realized in D-O-ZIS with a remarkable solar-to-hydrogen conversion efficiency of 0.57%, accompanying a ~ 91% retention rate after 120 h photocatalytic test. In this work, we inspire an universal design from electronegativity differences perspective to activate and stabilize metal sulfide photocatalysts for efficient overall water-splitting.

Abstract Antibody-drug conjugates (ADCs) represent an important class of cancer therapies that have revolutionized the treatment paradigm of solid tumors. To date, many ongoing studies of ADC combinations with a variety of anticancer drugs, encompassing chemotherapy, molecularly targeted agents, and immunotherapy, are being rigorously conducted in both preclinical studies and clinical trial settings. Nevertheless, combination therapy does not always guarantee a synergistic or additive effect and may entail overlapping toxicity risks. Therefore, understanding the current status and underlying mechanisms of ADC combination therapy is urgently required. This comprehensive review analyzes existing evidence concerning the additive or synergistic effect of ADCs with other classes of oncology medicines. Here, we discuss the biological mechanisms of different ADC combination therapy strategies, provide prominent examples, and assess their benefits and challenges. Finally, we discuss future opportunities for ADC combination therapy in clinical practice.

Abstract B-cell lymphoma 2 (Bcl-2)-associated athanogene (BAG) family genes play prominent roles in regulating plant growth, development, and stress response. Although the molecular mechanism underlying BAG’s response to abiotic stress has been studied in Arabidopsis, the function of OsBAG underlying saline-alkaline stress tolerance in rice remains unclear. In this study, OsBAG6, a chaperone regulator localized to mitochondria, was identified as a novel negative regulator of saline-alkaline stress tolerance in rice. The expression level of OsBAG6 was induced by high concentration of salt, high pH, heat and abscisic acid treatments. Overexpression of OsBAG6 in rice resulted in significantly reduced plant heights, grain size, grain weight, as well as higher sensitivity to saline-alkaline stress. By contrast, the osbag6 loss-of-function mutants exhibited decreased sensitivity to saline-alkaline stress. The transcriptomic analysis uncovered differentially expressed genes related to the function of “response to oxidative stress”, “defense response”, and “secondary metabolite biosynthetic process” in the shoots and roots of OsBAG6-overexpressing transgenic lines. Furthermore, cytoplasmic levels of Ca2+ increase rapidly in plants exposed to saline-alkaline stress. OsBAG6 bound to calcium sensor OsCaM1-1 under normal conditions, which was identified by comparative interactomics, but not in the presence of elevated Ca2+. Released OsCaM1-1 saturated with Ca2+ is then able to regulate downstream stress-responsive genes as part of the response to saline-alkaline stress. OsBAG6 also interacted with energy biosynthesis and metabolic pathway proteins that are involved in plant growth and saline-alkaline stress response mechanisms. This study reveals a novel function for mitochondrial localized OsBAG6 proteins in the saline-alkaline stress response alongside OsCaM1-1.

Abstract The biomechanical characteristics of runs in firefighters with different rescue tasks are unclear. This study aimed to explore the biomechanical characteristics of firefighters running in different rescue tasks and provide theoretical and practical references for firefighter training and occupational injury prevention. Eighteen professional healthy male firefighters were randomly selected as participants and tested running on different rescue tasks: wearing firefighting protective clothing (FPC), FPC+carrying a gas can (20 kg, FPC+ C), and FPC+carrying a mannequin (60 kg, FPC+M). Eight Qualisys infrared cameras and an AMTI 3D force measurement platform were used for the participant's acquisition of lower limb kinematic/kinetic data. The results showed that gait velocity and stride length of the FPC+GC and FPC+ M rescue tasks were significantly decreased compared to the FPC rescue task, while the support time was significantly increased. Compared to the FPC rescue task, the FPC+GC rescue task showed significant decreases in vertical ground reaction force (vGRF), minimum ankle dorsiflexion angle, and the maximum ankle plantarflexion power. In contrast, the FPC+M rescue task demonstrated significant increases in ankle range of motion, maximum hip extension angle, minimum knee flexion angle, maximum ankle dorsiflexion angle, maximum hip extension moment, maximum knee flexion moment, maximum hip flexion power, and hip and knee stiffness while exhibiting significant decreases in minimum ankle dorsiflexion angle. Compared to the FPC+ GC rescue task, the FPC+M rescue task exhibited significant increases in the maximum hip extension angle, minimum knee flexion angle, maximum ankle dorsiflexion angle, maximum hip flexion moment, maximum hip extension moment, maximum knee flexion moment, maximum ankle plantarflexion moment, maximum hip flexion power, maximum ankle dorsiflexion power, hip stiffness, and vGRF. Conversely, it showed significant decreases in the maximum knee flexion power. In conclusion, compared to the FPC rescue task, the FPC+GC and FPC+M rescue tasks altered the firefighter's gait performance, as evidenced by decreased gait velocity and stride length and increased support time. FPC+M rescue task would increase firefighter's risk of hip and knee injuries. Therefore, we suggest firefighters increase their strength training of the trunk, hip, and knee joint muscles as part of their daily training programs under large weight load status (60 kg and above) to reduce injury risk during rescue tasks.

In this study, the amorphous carbon (a-C) films were deposited using HiPIMS and DCMS at same average power. The composition, microstructure and the anti-tribocorrosion property at hydrostatic pressure environment were investigated in detail. The results showed the HiPIMS:a-C film exhibited a higher fraction of sp3 bonding (59 %) compared to DCMS. The increased sp3 fraction led to improved mechanical properties and significantly enhanced the film's capacity loading during sliding. Furthermore, due to the denser structure, the HiPIMS:a-C film demonstrated enhanced localized corrosion resistance at 30 MPa, which can be attributed to its lower defect density. These findings highlight the substantial advantage of HiPIMS in producing high-performance a-C films suitable for harsh deep-sea environments.

ABSTRACTThe evolution and future trajectory of island shorelines, amidst global climate change, are of increasing concern to governments, communities and researchers worldwide. However, the field of island studies is often hampered by a lack of data and inconsistent methodologies, leading to an inadequate understanding of the processes driving shoreline changes on islands within the context of climate change. This research aims to bridge this gap by analyzing islands in Southeast Asia, the Indian Ocean and the Mediterranean Sea from 1990 to 2020 using remote sensing. Of over 13,000 islands examined, approximately 12% experienced significant shifts in shoreline positions. The total shoreline length of these islands approaches 200,000 km, with 7.57% showing signs of landward erosion and 6.05% expanding seaward. Human activities, particularly reclamation and land filling, were identified as primary drivers of local shoreline transformations, while natural factors have a comparatively minor impact. Moreover, the ongoing rise in sea levels is identified as an exacerbating factor for coastal erosion rather than the primary cause. Drawing from these findings, we propose several adaptive measures for islands in response to climate change. Taken together, this research provides comprehensive data and a basis for decision-making for sustainable development of island territories.

ABSTRACTSoil moisture plays a crucial role in understanding the hydrological cycle and the ecological environment. This research presents an improved change detection method that leverages time series data from Sentinel-1 radar and Sentinel-2 optical sensors (2019–2021) to estimate surface soil moisture. The response of backscatter to soil moisture in bare soil was expressed in a logarithmic form, and the influence function of the normalized difference vegetation index (NDVI) on the backscatter difference was established for various vegetation-covered surfaces. Therefore, the impact of vegetation on backscatter is effectively mitigated, and the resulting change in backscatter relative to bare soil conditions can be obtained. An empirical function is subsequently formulated to ascertain the reference values of soil moisture in each pixel. The retrieval of soil moisture is demonstrated in the Wudaoliang permafrost region of the Qinghai-Tibet Plateau and validated against ground measurements. The retrieval results of the improved change detection method exhibit correlation coefficients ranging from 0.672 to 0.941, with root mean squared errors (RMSE) ranging from 0.031 [Formula: see text] to 0.073 [Formula: see text]. Compared to the Soil Moisture Active Passive (SMAP) 9-km product, our new method demonstrates higher correlation (0.898 vs. 0.867) and lower RMSE (0.037 [Formula: see text] vs. 0.044[Formula: see text]). The soil moisture retrieved from Sentinel shows a strong correlation with the SMAP 9-km soil moisture in the time series, thereby providing a better representation of the region’s soil moisture heterogeneity. Our method demonstrates the feasibility of combining Sentinel-1 and 2 for high-resolution (100 m) soil moisture mapping in permafrost regions.

Although thermosonication (TS) treatment has been widely used in food sterilization, the viable but non‐culturable (VBNC) of bacteria with TS treatment has still concerned potential food safety and public health. The molecular mechanism of VBNC status of bacteria with TS treatment is not clearly known. Therefore, in this study, we used Shewanella putrefaciens, which was a common putrefactive bacteria in aquatic products, to study the VBNC state of bacteria with TS treatment. Firstly, our results revealed that S. putrefaciens still could enter the VBNC state after TS treatments: 50 kHz, 300 W, 30 min ultrasonic treatment and 70 °C heating; Subsequently, we found the VBNC state of S. putrefaciens can resist the damage of TS treatment, such as cell wall break, DNA degradation, etc; Finally, four-dimensional data-independent acquisition-based proteomics showed that under VBNC state, S. putrefaciens upregulated functional proteins to resist TS treatment, such as: ribosomal proteins to accelerate the synthesis of stress proteins to counteract TS treatments, ornithine decarboxylase SpeF and MraY to repair TS treatment-induced damage, etc. Meanwhile, S. putrefaciens downregulates metabolic and transport functional proteins such as dehydrogenase to reduce the metabolism. Importantly, among those proteins, the ribosomal transcriptional regulatory protein family, such as rpsB, etc, may be the key proteins for S. putrefaciens entering VBNC state. This finding can provide some new strategies for preventing VBNC status of bacteria with TS treatment, such as: inhibition of key proteins, etc.

Abstract Habitat is fundamental for facilitating various life activities in animals, for instance, snakes procure essential energy for survival and reproduction by selecting ambush microhabitats. While there has been extensive research on the selection of microhabitat for feeding in terrestrial and aquatic snakes, little is known about arboreal snakes. In the present study, we analyzed the ambush microhabitat preferences of Viridovipera stejnegeri, a widely distributed Asian pitviper in China, conducted association analysis between snake microhabitat and prey microhabitat and abundance to determine the ro5le of microhabitat selection in feeding. Employing random forest analysis and habitat selection functions, we further constructed a predictive framework for assessing the probability of ambush site selection by V. stejnegeri. Our results revealed that V. stejnegeri exhibited a distinct microhabitat preference for ambush prey. Among the 13 environmental factors assessed, V. stejnegeri showed pronounced preferences towards 12 of these factors, including climatic factors, geographical factors, and vegetation factors. Furthermore, although the preferences of V. stejnegeri overlapped substantially with those of its prey across multiple habitat factors, food abundance shows no significant association with various habitat factors of V. stejnegeri, and does not have significant predictive effect on habitat selection of V. stejnegeri. Therefore, we infer that V. stejnegeri does not preferentially select microhabitats with the highest food abundance, which does not support the hypothesis that “snakes select habitats based on the spatial distribution of prey abundance.” By analyzing the characteristics of vegetation, geography, and climate, we conclude that V. stejnegeri tends to choose microhabitats with better ambush conditions to increase attack success rate, thereby achieving the optimal feeding success rate at the microhabitat scale, which is in line with the predictions of optimal foraging theory. This study provides new insights into the predation ecology and habitat selection of snakes.

Abstract Although several phylogeographic studies of Asian snakes have been conducted, most have focused on pitvipers, with non‐venomous snakes, such as colubrids or natricids, remaining poorly studied. The Chinese keelback water snake (Trimerodytes percarinatus Boulenger) is a widespread, semiaquatic, non‐venomous species occurring in China and southeastern Asia. Based on mitochondrial DNA (mtDNA) and single nucleotide polymorphism (SNP) data, we explored the population genetic structure, genetic diversity, and evolutionary history of this species. MtDNA‐based phylogenetic analysis showed that T. percarinatus was composed of five highly supported and geographically structured lineages. SNP‐based phylogenetic analysis, principal component analysis, and population structure analysis consistently revealed four distinct, geographically non‐overlapping lineages, which was different from the mtDNA‐based analysis in topology. Estimation of divergence dates and ancestral area of origin suggest that T. percarinatus originated ~12.68 million years ago (95% highest posterior density: 10.36–15.96 Mya) in a region covering southwestern China and Vietnam. Intraspecific divergence may have been triggered by the Qinghai‐Xizang Plateau uplift. Population demographics and ecological niche modeling indicated that the effective population size fluctuated during 0.5 Mya and 0.002 Mya. Based on the data collected here, we also comment on the intraspecific taxonomy of T. percarinatus and question the validity of the subspecies T. p. suriki.

Engineered noble metal nanomaterials (NMN) possess adjustable optical, electrical, and biocompatible properties that make them excellent tools for probing the nano‐bio‐interface. Understanding their interactions with biomolecules, cells, and tissues at the nano‐bio‐interface is crucial in designing these nanomaterials for biomedical applications. This review summarizes the structure, properties, synthesis, and passivation methods of noble metal nanoparticles, as well as the construction strategy and detection technology of the nano‐bio‐interface to provide important information about their uptake, distribution, metabolism, and degradation in vivo and in vitro. The related action mechanisms include the kinetic and thermodynamic processes of the nano‐bio‐interface, the driving forces for its formation, and the chemical reactions at the nano‐bio‐interface. By exploring the action mechanism of the nano‐bio‐interface, the antibacterial properties and cytotoxicity of NMN could be better understood, and open up more extensive biological applications. Finally, the future trends of NMNs in the biological field and the challenges encountered in realizing these technologies are discussed.

PurposeTo compare the prognosis of complete and insufficient ablation of transarterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) in treating medium and large hepatocellular carcinoma (HCC) and to explore the differences in recurrence patterns between the two groupsPatients and methodsPatients´ medical records and imaging data of patients with confirmed HCC from January 2014 to January 2022 were collected. These patients were divided into 2 groups: complete ablation (n=172) and insufficient ablation (n=171). Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier curve and the log-rank test was used to compared. Fisher’s exact test was used to compare recurrence patterns between the two groups.ResultsThe median OS time was 72.8 months (95%CI:69.5-76.1) and 62.0 months (95%CI: 55.3-68.7) in the complete and insufficient ablation groups, respectively. The median PFS time in the complete ablation group was 67.8 months (95% CI: 65.2-70.4) and 38.6 months (95%CI: 29.8-47.4) in the insufficient ablation group. The OS and PFS rates of the complete ablation group were significantly better than those of the insufficient ablation group (P

AbstractHuman papillomavirus (HPV) infection and related diseases are clinical challenges. The efficacy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) using red laser (630 ± 5 nm) is remarkable and safe. In this study, we aim to investigate the efficacy of ALA-450 nm PDT comparing with ALA-635 nm PDT. We detected cell proliferation and cell apoptosis through MTT assay and flow cytometry assay respectively. Flow cytometry assay determined the intracellular reactive oxygen species (ROS) generation. Western blotting analysis investigated the protein expression. In vivo, immunohistochemical staining assay and TUNEL assay were performer to detect cell apoptosis. ALA-450 nm PDT inhibited the proliferation of End1 and HeLa cells, promoted cell apoptosis more effectively than ALA-635 nm PDT, and induced cell death probably through increasing the intracellular ROS generation and caspase-dependent apoptosis pathway. In vivo, ALA-450 nm PDT significantly inhibited tumour growth and activated cell apoptosis. The ALA-450 nm PDT had an advantage over ALA-635 nm PDT on inhibiting the proliferation of End1 and HeLa cells and inducing cell apoptosis. The ALA-450 nm PDT might be a promising therapeutic strategy for eradicating the HR-HPV infected cells and promoting the integration of diagnosis and treatment of HR-HPV related diseases.HighlightsWe combined 5-aminolevulinic acid with 450 nm blue laser using as a novel type of photodynamic therapy.The ALA-450 nm PDT had an advantage over ALA-635 nm PDT on inhibition of the proliferation of End1 and HeLa cells and inducing cell apoptosis in vitro and in vivo.The ALA-450 nm PDT may provide a novel alternative therapeutic option in patients with persistent HPV infection and promote the integration of diagnosis and treatment.

Abstract Background Due to the fact that the CT-occult central lung squamous cell carcinoma and squamous epithelial precancerous lesions. (CT-occult CLSCC and SEPL) cannot be detected by lung CT screening, early and timely diagnosis of central lung cancer becomes very difficult, which directly affects the prognosis of patients. Methods We retrospectively review medical records of patients at the Zhejiang Cancer Hospital and enrolled 41 patients with the CT-occult CLSCC and SEPL and 48 patients without the CT-occult CLSCC and SEPL. We compare the clinical characteristics, imaging features and Changes in the number of pixels under different CT value intervals of patients with and without the CT-occult CLSCC and SEPL and we perform univariate and multivariate logistic regression analysis to explore independent factors for the CT-occult CLSCC and SEPL in the patients. Results We demonstrate that pack-years ≥ 20 (OR: 3.848, 95% CI: 1.086 ~ 13.633), the number of pixels change of CT value in interval [-850 ~ -750HU] (OR: 5.302, 95% CI: 1.122 ~ 25.057) and in interval [-900 ~ -850HU] (OR: 3.478, 95% CI: 1.167 ~ 10.365) are independently associated with the CT-occult CLSCC and SEPL in the patients. Ultimately, the logistic model obtained is statistically significant (p

Abstract Background Colorectal cancer is a common malignant tumour. Invasive growth and distant metastasis are the main characteristics of its malignant biological behaviour, and they are also the primary factors leading to death in colon cancer patients. Atovaquone is an antimalarial drug, and its anticancer effect has recently been demonstrated in several cancer models in vitro and in vivo, but it has not been examined in the treatment of colorectal cancer. Methods To elucidate the effect of atovaquone on colorectal cancer. We used RNA transcriptome sequencing, RT‒PCR and Western blot experiments to examine the expression of NF-κB (p-P65), EMT-related proteins and related inflammatory factors (IL1B, IL6, CCL20, CCL2, CXCL8, CXCL6, IL6ST, FAS, IL10 and IL1A). The effect of atovaquone on colorectal cancer metastasis was validated using an animal model of lung metastases. We further used transcriptome sequencing, the GCBI bioinformatics database and the STRING database to predict relevant target proteins. Furthermore, pathological sections were collected from relevant cases for immunohistochemical verification. Results This study showed that atovaquone could inhibit colorectal cancer metastasis and invasion in vivo and in vitro, inhibit the expression of E-cadherin protein, and promote the protein expression of N-cadherin, vimentin, ZEB1, Snail and Slug. Atovaquone could inhibit EMT by inhibiting NF-κB (p-P65) and related inflammatory factors. Further bioinformatics analysis and verification showed that PDGFRβ was one of the targets of atovaquone. Conclusion In summary, atovaquone can inhibit the expression of NF-κB (p-P65) and related inflammatory factors by inhibiting the protein expression of p-PDGFRβ, thereby inhibiting colorectal cancer metastasis. Atovaquone may be a promising drug for the treatment of colorectal cancer metastasis.

Abstract Because China produces the most crayfish in the world, safe solutions must be improved to mitigate the risks of ongoing heavy metal stressors accumulation. This study aimed to use Saccharomyces cerevisiae as a bioremediation agent to counteract the harmful effect of cadmium (Cd) on crayfish (Procambarus clarkia). Our study used three concentrations of S. cerevisiae on crayfish feed to assess their Cd toxicity remediation effect by measuring total antioxidant capacity (TAC) and the biomarkers related to oxidative stress like malondialdehyde (MDA), protein carbonyl derivates (PCO), and DNA–protein crosslink (DPC). A graphite furnace atomic absorption spectroscopy device was used to determine Cd contents in crayfish. Furthermore, the mRNA expression levels of lysozyme (LSZ), metallothionein (MT), and prophenoloxidase (proPO) were evaluated before and following the addition of S. cerevisiae. The results indicated that S. cerevisae at 5% supplemented in fundamental feed exhibited the best removal effect, and Cd removal rates at days 4th, 8th, 12th, and 21st were 12, 19, 29.7, and 66.45%, respectively, which were significantly higher than the basal diet of crayfish. The addition of S. cerevisiae increased TAC levels. On the other hand, it decreased MDA, PCO, and DPC, which had risen due to Cd exposure. Furthermore, it increased the expression of proPO, which was reduced by Cd exposure, and decreased the expression of LSZ and MT, acting in the opposite direction of Cd exposure alone. These findings demonstrated that feeding S. cerevisiae effectively reduces the Cd from crayfish and could be used to develop Cd-free crayfish-based foods.

Abstract Background Microvascular dysfunction is one of the most common pathological characteristics in Type 2 diabetes. Human mesenchymal stem cell-derived exosomes (hUCMSCs-Exo) have diverse functions in improving microcirculation; however, the molecular mechanism of hUCMSCs-Exo in regulating burn-induced inflammation is not well understood. Methods hUCMSCs-Exo were extracted by hypervelocity centrifugation method, and exosome morphology was observed by transmission electron microscopy, exosome diameter distribution was detected by particle size analysis, and exosome specific proteins were identified by Western blot.2. DB/DB mice were randomly divided into exosomes group and PBS group. Exosomes and PBS were injected into the tail vein, respectively, and the calf muscle tissue was taken 28 days later. 0.5% Evans blue fluorescence assessment microvascular permeability. The expression of CD31 was detected by immunofluorescence.The morphology and function of microvessels in muscle tissue of lower limbs was evaluated by transmission electron microscopy.3. TMT proteomics was used to detect the changes of differential protein expression in lower limb muscle tissues of the PBS group and the exosome group, and data analysis was performed to screen key signal molecules and their involved biological pathways. Key signal molecules CD105 were verified by Western blot. The expression of TGF-β1 in exosomes were evaluated by Western blot. Results Electron microscopy showed that hUCMSCs-Exo presented a uniform vesicle structure, and NTA showed that its diameter was about 160 nm. Western blot showed positive expression of specific proteins CD9, CD81 and TSG101 on exosomes.2. There is no significant change in blood glucose and body weight before and after the exosome treatment. The exosome group can significantly reduce the exudation of Evans blue. Compared with the PBS group. Meanwhile, CD31 immunofluorescence showed that the red fluorescence of exosome treatment was significantly increased, which was higher than that of PBS group. Transmission electron microscopy showed smooth capillary lumen and smooth and complete surface of endothelial cells in the exosome group, while narrow capillary lumen and fingerlike protrusion of endothelial cells in the PBS group.3.Quantitative analysis of TMT proteomics showed that there were 82 differential proteins, including 49 down-regulated proteins and 33 up-regulated proteins. Go enrichment analysis showed that the differential proteins were involved in molecular function, biological process, cell components,among which CD105 was one of the up-regulated proteins. Through literature search, CD105 was found to be related to endothelial cell proliferation. Therefore, this study verified the changes of CD105 in the exosome group, and it was used as the mechanism study of this study. 4. Western blot analysis showed that the expression of CD105 protein in lower limb muscle tissue of exosome group was significantly increased compared with that of PBS group. Based on the fact that CD105 is a component of the TGF-β1 receptor complex and exosomes are rich in growth factors and cytokines, this study further examined the expression of TGF-β1 in exosomes, and the results showed that exosomes had high expression of TGF-β1. Conclusion By improving the integrity of microvascular endothelial cells, hUCMSCs-Exo can improve the permeability of microvessels in diabetic lower muscle tissue, further promote the proliferation of lower limb muscle cells and inhibit the apoptosis of tissue cells. The mechanism may be associated with exosomes rich in TGF-β1, which is likely to promote endothelial cell proliferation and improve permeability through binding to the endothelial CD105/TβR-II receptor complex, while promoting angiogenesis and protecting skeletal muscle cells from apoptosis.

A new species of Xenophrys is described from Yadong County, Tibet Autonomous Region, China based on morphological and molecular evidence. Phylogenetic analyses based on the mitochondrial genes 16S rRNA and COI indicated that this new species represents an independent lineage and the minimum p-distance based on 16S rRNA between this species and its congeners is 4.4%. Additionally, the new species is distinguished from its congeners by a combination of the following morphological characters: (1) small body size, SVL 17.9–22.2 mm in adult males and SVL 23.4 mm in the single adult female; (2) tympanum indistinct, supratympanic fold distinct; (3) canthus rostralis well-developed, snout tip far beyond the margin of the lower lip; (5) pupil vertical; (6) vomerine teeth present, maxillary teeth present; (7) tongue notched posteriorly; (8) supernumerary tubercles absent, subarticular, metacarpal and metatarsal tubercles indistinct; (9) relative finger lengths I < II < IV < III, finger tips rounded, slightly expanded relative to digit widths; (10) toes with narrow lateral fringes and tarsal folds; (11) a dark triangular marking with light edge between eyes, a dark “)(”-shaped marking, with light edge, present on center of dorsum, pectoral glands on sides of the breast.

The objective of this study is to investigate the storage stability and rheological property of bio-oil/lignin composite-modified asphalt. The composite-modified asphalt with different proportions of bio-oil was prepared and cured at 105 °C, 135 °C, and 165 °C for 24 h and 48 h. The storage stability of the composite-modified asphalt was evaluated based on the softening point difference, the storage stability index derived from rotational viscosity, the segregation rate based on temperature sweep, and the non-recoverable creep compliance measured through the Multiple Stress Creep Recovery test. The storage stability of bio-oil/lignin composite-modified asphalt was evaluated through testing and analysis of its infrared spectroscopy and scanning electron microscopy before and after thermal storage. The research results indicate that the maximum difference in softening point is 0.9 °C, and the calculated storage stability index is generally below 0.1. The maximum value of the segregation rate is 0.43, indicating excellent storage stability of the bio-oil/lignin composite-modified asphalt. According to the results from infrared spectroscopy, no chemical reactions occurred during the storage process of the composite-modified asphalt. The scanning electron microscope confirmed that the samples became more stable after 48 h of storage.

Bacterial resistance to antibiotics can lead to long-lasting, hard-to-cure infections that pose significant threats to human health. One key mechanism of antimicrobial resistance (AMR) is to reduce the antibiotic permeation of cellular membranes. For instance, the lack of outer membrane porins (OMPs) can lead to elevated AMR levels. However, knowledge on whether mutations of OMPs can also influence antibiotic susceptibility is limited. This work aims to address this question and identified an A226D mutation in OmpC, a trimeric OMP, in Escherichia coli. Surveillance studies found that this mutation is present in 50 E. coli strains for which whole genomic sequences are available. Measurement of minimum inhibition concentrations (MICs) found that this mutation leads to a 2-fold decrease in MICs for β-lactams ampicillin and piperacillin. Further survival assays confirmed the role this mutation plays in β-lactam susceptibility. With molecular dynamics, we found that the A226D mutation led to increased overall flexibility of the protein, thus facilitating antibiotic uptake, and that binding with piperacillin was weakened, leading to easier antibiotic penetration. This work reports a novel mutation that plays a role in antibiotic susceptibility, along with mechanistic studies, and further confirms the role of OMPs in bacterial tolerance to antibiotics.

Environmental variations initiate chromatin modifications, leading to the exchange of histone subunits or the repositioning of nucleosomes. The phosphorylated histone variant H2A.X (γH2A.X) is recognized for the formation of foci that serve as established markers of DNA double-strand breaks (DSBs). Nevertheless, the precise roles of H2A.X in the cellular response to genotoxic stress and the impact of the plant hormone abscisic acid (ABA) remain incompletely understood. In this investigation, we implemented CRISPR/Cas9 technology to produce loss-of-function mutants of AtHTA3 and AtHTA5 in Arabidopsis. The phenotypes of the athta3 and athta5 single mutants were nearly identical to those of the wild-type Col-0. Nevertheless, the athta3 athta5 double mutants exhibited aberrant embryonic development, increased sensitivity to DNA damage, and higher sensitivity to ABA. The RT-qPCR analysis indicates that AtHTA3 and AtHTA5 negatively regulate the expression of AtABI3, a fundamental regulator in the ABA signaling pathway. Subsequent investigation demonstrated that AtABI3 participates in the genotoxic stress response by influencing the expression of DNA damage response genes, such as AtBRCA1, AtRAD51, and AtWEE1. Our research offers new insights into the role of H2A.X in the genotoxic and ABA responses of Arabidopsis.

The visibility of retail frontages is critical for earning profits from spontaneous traffic visits to retail shops located along a street. The urban tree canopy plays a crucial role in enhancing the street-side environment, yet more is not always better when considering the placement of retail shops behind trees with big canopies. Related evidence in the literature is rarely provided, and an unclear relationship has been reported to exist between the number of shops for a specific retail type and the quantified ratio of the canopy shade in a street view. In this study, both big data crawling and deep learning were employed to unravel this relationship for retail shops in Changchun, Northeast China. The entire study area was divided into 6037 grid cells with a side length of ~0.6 km, wherein the number of shops of five retail types (food and beverage, shopping, life services, entertainment, and hotel) were quantified by computer counting their points of interest (POIs). The canopy shade was evaluated using the green view index (GVI) quantified through the ratio of canopy pixels divided by all the pixels in a street view image obtained through an online map API. A neighboring road network was categorized into four classes: class I road density mainly reduced the number of retail shops, and the road densities of classes III and IV accounted for more retail shops. The relationship between the number of retail shops and the GVI could be fitted with positive skewness curves for class II roads, where the critical peak of the GVI was estimated to be about 3.27%. The optimization scheme indicated that more retail shops should be placed along class I and II roads. In conclusion, more retail shops for food and beverage, shopping, and life services should be placed in the landscape neighboring big canopies.

Federated learning is an effective approach for preserving data privacy and security, enabling machine learning to occur in a distributed environment and promoting its development. However, an urgent problem that needs to be addressed is how to encourage active client participation in federated learning. The Shapley value, a classical concept in cooperative game theory, has been utilized for data valuation in machine learning services. Nevertheless, existing numerical evaluation schemes based on the Shapley value are impractical, as they necessitate additional model training, leading to increased communication overhead. Moreover, participants’ data may exhibit Non-IID characteristics, posing a significant challenge to evaluating participant contributions. Non-IID data have greatly affected the accuracy of the global model, weakened the marginal effect of the participants, and led to the underestimated contribution measurement results of the participants. Current work often overlooks the impact of heterogeneity on model aggregation. This paper presents a fair federated learning contribution measurement scheme that addresses the need for additional model computations. By introducing a novel aggregation weight, it enhances the accuracy of the contribution measurement. Experiments on the MNIST and Fashion MNIST dataset show that the proposed method can accurately compute the contributions of participants. Compared to existing baseline algorithms, the model accuracy is significantly improved, with a similar time cost.

The objective of this study was to investigate the umami characteristics of soy sauce using electronic tongue evaluation and amino acid composition and matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI−TOF MS) analysis. The soy sauce peptides were isolated from soy sauce using XAD−16 macroporous resin combined with ethanol solution. The results showed that the soy sauce peptide fraction eluted by 60% ethanol (SS−60%) exhibited a prominent umami taste, and the umami scores were highly positively correlated with the amino acid nitrogen contents of soy sauces. The umami scores of SS−60% were significantly positively correlated with the contents of free amino acids. Especially, Phe showed the highest positive correlation with the umami scores. In addition, five characteristic ion peaks with m/z at 499, 561, 643, 649, and 855 were identified in the peptide mass fingerprinting. Therefore, this study provides new insights into the umami characteristics for the taste evaluation and reality identification of soy sauce.

Plasma bubbles represent notable ionospheric irregularities primarily observed in low latitudes, characterized by plasma depletions exhibiting large spatial scales, which can make a significant impact on the propagation of OTHR (over-the-horizon radar) waves. Firstly, we constructed a three-dimensional model of plasma bubbles, which is modulated by Gaussian function distribution in the horizontal direction, and then we analyzed the impact of EPBs (Equatorial Plasma Bubbles) on the ray path of OTHR shortwaves. When radio waves propagate through EPBs with different RMS ΔN/N, there is a significant difference in the propagation path of OTHR waves. For the EPB with an RMS ΔN/N of 75%, radio waves exhibit more pronounced refraction than those with lower RMS values, the focusing effect of radio waves is more obvious, and the focusing point is relatively lower. In terms of different seasons, OTHR shortwaves propagating through EPBs exhibit different degrees of refraction. In addition, radio waves show the effect of inward focusing in different seasons: the focusing effect is the most pronounced in spring, followed by autumn, then summer, and the weakest in winter. For different solar activities, the impact of EPBs on OTHR shortwaves is more significant in the high-solar-activity year.

BackgroundMalnutrition is the most common nutritional issue in Alzheimer’s disease (AD) patients, but there is still a lack of a comprehensive evaluation of the nutritional status in AD patients. This study aimed to determine the potential association of various nutritional indices with AD at different stages.MethodsSubjects, including individuals with normal cognition (NC) and patients diagnosed with AD, were consecutively enrolled in this cross-sectional study. Demographics, body composition, dietary patterns, nutritional assessment scales and nutrition-related laboratory variables were collected. Binary logistics regression analyses and receiver operating characteristic (ROC) curves were used to indicate the association between nutrition-related variables and AD at different stages.ResultsTotals of 266 subjects, including 73 subjects with NC, 72 subjects with mild cognitive impairment due to AD (AD-MCI) and 121 subjects with dementia due to AD (AD-D) were included. There was no significant difference in dietary patterns, including Mediterranean diet and Mediterranean-DASH diet intervention for neurodegenerative delay (MIND) diet between the three groups. Lower BMI value, smaller hip and calf circumferences, lower Mini Nutritional Assessment (MNA) and Geriatric Nutritional Risk Index (GNRI) scores, and lower levels of total protein, albumin, globulin, and apolipoprotein A1 were associated with AD (all p

The negative impacts of anthropogenic disturbances on the ecology of small island states or regions are important topics mentioned by United Nations' Sustainable Development Goals. This study used the coastline as an indicator to analyze four parameters (the annual variation rate of the artificial coastline length, the index of coastline utilization degree, the index of coastline type diversity, and the standard deviation ellipse of the latter two indicators) to study the changing characteristics of coastal development and utilization of over 13,000 islands, revealing the spatiotemporal evolution characteristics and patterns of human disturbance in island coastal zones. The results indicated that:(1) The spatial–temporal patterns of coastline length and structure undergone significant changes. The length of artificial coastline increased, while natural coastline decreased. The most pronounced change in the artificial coastline was the proliferation of aquaculture embankments, and the most drastic changes occurred in the coastal areas of Southeast Asia.(2) The intensity of coastal development and utilization, as well as the diversity of coastline types, showed an upward trend on the islands. (3) The centroid of coastline utilization degree and type diversity both shifted southeastward by 59.53 km and 931.05 km, respectively. (4) The anthropogenic disturbance patterns on the islands primarily included land reclamation and occupation of original wetland systems. Our study revealed the spatiotemporal characteristics and multiple scenario patterns of anthropogenic disturbance on islands at a large spatial scale from 1990 to 2020, and we quantitatively analyzed the relationship between anthropogenic disturbance factors and changes in the coastline of islands. Islands are currently facing significant pressures from development and conservation. This work is of great significance for the study of sustainable development and management of islands experiencing high-intensity human activities.

Accurately portraying the mechanism of the flow of natural resource consumption between regions and its impact on ecology is of crucial value in deepening the understanding of the coordinated relationship between population, resources, environment and development. Consequently, this promotes the sustainable development of the natural economy and society. Based on a regional-industrial perspective, this study used a localized three-dimensional ecological footprint model to measure and decompose natural resources in Xinjiang from 2005 to 2020. In doing so, the study clarified the supply, demand, and flow utilization of natural capital in Xinjiang, the balance of spatial and temporal allocation of resources, the coupling between economic growth and resource consumption, and the coordination between industrial structure and ecological environment. The results showed that (1) Xinjiang's per capita ecological deficit grew from 2.096 to 11.667 in 2005–2020. Moreover, the energy footprint was a decisive part of the ecological deficit throughout the study period. Furthermore, the trend of increased ecological pressure was higher in northern and eastern Xinjiang than in southern Xinjiang. (2) The overall Gini coefficient of Xinjiang's ecological carrying capacity was at the critical value of spatial equilibrium (0.4), with differences between the groups: Northern & Southern Xinjiang > Northern & Eastern Xinjiang > Eastern & Southern Xinjiang. The reasons for this inter-regional economic disparity are related to fiscal expenditure/GDP, level of urbanization, and regional industrial output. Overall, the decoupling relationship between environmental pressures and economic growth was optimistic. (3) From an industrial perspective, the levels of industrial structural efficiency and the industrial ecological harmony index were still relatively low, but the overall trend was on the rise. (4) Resource endowment, economic development, consumption structure, and population had significant driving effects on the ecological footprint, whereas environmental protection, science, and technology could inhibit its growth to a certain extent. This study aimed to provide an in-depth analysis of the current situation and problems of natural resource use in Xinjiang and provide theoretical and practical references for sustainable development in the region.

Abstract Understanding the adsorption interactions between carbon materials and sulfur compounds has far‐reaching impacts, in addition to their well‐known important role in energy storage and conversion, such as lithium‐ion batteries. In this paper, properties of intrinsic B or Si single‐atom doped, and B–Si codoped graphene (GR) and graphdiyne (GDY) were investigated by using density functional theory‐based calculations, in which the optimal doping configurations were explored for potential applications in adsorbing sulfur compounds. Results showed that both B or Si single‐atom doping and B–Si codoping could substantially enhance the electron transport properties of GR and GDY, improving their surface activity. Notably, B and Si atoms displayed synergistic effects for the codoped configurations, where B–Si codoped GR/GDY exhibited much better performance in the adsorption of sulfur‐containing chemicals than single‐atom doped systems. In addition, results demonstrated that, after B–Si codoping, the adsorption energy and charge transfer amounts of GDY with sulfur compounds were much larger than those of GR, indicating that B–Si codoped GDY might be a favorable material for more effectively interacting with sulfur reagents.