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Vegetation greening has long been acknowledged, but recent studies have pointed out that vegetation greening is possibly stalled or even reversed. However, detailed analyses about greening reversal or increased browning of vegetation remain scarce. In this study, we utilized the normalized difference vegetation index (NDVI) as an indicator of vegetation to investigate the trends of vegetation greening and browning (monotonic, interruption, and reversal) through the breaks for the additive season and trend (BFAST) method across China’s drylands from 1982 to 2022. It also reveals the impacts of ecological restoration programs (ERPs) and climate change on these vegetation trends. We find that the vegetation displays an obvious pattern of east-greening and west-browning in China’s drylands. Greening trends mainly exhibits monotonic greening (29.8 %) and greening with setback (36.8 %), whereas browning shows a greening to browning reversal (19.2 %). The increase rate of greening to browning reversal is 0.0342/yr, which is apparently greater than that of greening with setback, 0.0078/yr. This research highlights that, under the background of widespread vegetation greening, vegetation browning is progressively increasing due to the effects of climate change. Furthermore, the ERPs have significantly increased vegetation coverage, with the increase rate in 2000–2022 being twice as much as that of 1982–1999 in revegetation regions. Vegetation browning in southwestern Qingzang Plateau is primarily driven by adverse climatic factors and anthropogenic disturbances, which offset the efforts of ERPs.

Abstract Obesity shapes anti-tumor immunity through lipid metabolism; however, the mechanisms underlying how colorectal cancer (CRC) cells utilize lipids to suppress anti-tumor immunity remain unclear. Here, we show that tumor cell-intrinsic ATP6V0A1 drives exogenous cholesterol-induced immunosuppression in CRC. ATP6V0A1 facilitates cholesterol absorption in CRC cells through RAB guanine nucleotide exchange factor 1 (RABGEF1)-dependent endosome maturation, leading to cholesterol accumulation within the endoplasmic reticulum and elevated production of 24-hydroxycholesterol (24-OHC). ATP6V0A1-induced 24-OHC upregulates TGF-β1 by activating the liver X receptor (LXR) signaling. Subsequently, the release of TGF-β1 into the tumor microenvironment by CRC cells activates the SMAD3 pathway in memory CD8+ T cells, ultimately suppressing their anti-tumor activities. Moreover, we identify daclatasvir, a clinically used anti-hepatitis C virus (HCV) drug, as an ATP6V0A1 inhibitor that can effectively enhance the memory CD8+ T cell activity and suppress tumor growth in CRC. These findings shed light on the potential for ATP6V0A1-targeted immunotherapy in CRC.

Abstract Background The Atribacterota are widely distributed in the subsurface biosphere. Recently, the first Atribacterota isolate was described and the number of Atribacterota genome sequences retrieved from environmental samples has increased significantly; however, their diversity, physiology, ecology, and evolution remain poorly understood. Results We report the isolation of the second member of Atribacterota, Thermatribacter velox gen. nov., sp. nov., within a new family Thermatribacteraceae fam. nov., and the short-term laboratory cultivation of a member of the JS1 lineage, Phoenicimicrobium oleiphilum HX-OS.bin.34TS, both from a terrestrial oil reservoir. Physiological and metatranscriptomics analyses showed that Thermatribacter velox B11T and Phoenicimicrobium oleiphilum HX-OS.bin.34TS ferment sugars and n-alkanes, respectively, producing H2, CO2, and acetate as common products. Comparative genomics showed that all members of the Atribacterota lack a complete Wood-Ljungdahl Pathway (WLP), but that the Reductive Glycine Pathway (RGP) is widespread, indicating that the RGP, rather than WLP, is a central hub in Atribacterota metabolism. Ancestral character state reconstructions and phylogenetic analyses showed that key genes encoding the RGP (fdhA, fhs, folD, glyA, gcvT, gcvPAB, pdhD) and other central functions were gained independently in the two classes, Atribacteria (OP9) and Phoenicimicrobiia (JS1), after which they were inherited vertically; these genes included fumarate-adding enzymes (faeA; Phoenicimicrobiia only), the CODH/ACS complex (acsABCDE), and diverse hydrogenases (NiFe group 3b, 4b and FeFe group A3, C). Finally, we present genome-resolved community metabolic models showing the central roles of Atribacteria (OP9) and Phoenicimicrobiia (JS1) in acetate- and hydrocarbon-rich environments. Conclusion Our findings expand the knowledge of the diversity, physiology, ecology, and evolution of the phylum Atribacterota. This study is a starting point for promoting more incisive studies of their syntrophic biology and may guide the rational design of strategies to cultivate them in the laboratory. Video Abstract

Abstract Tumor-associated macrophages (TAMs) are a promising target for cancer immunotherapy, but delivering therapeutic agents to TAMs within the tumor microenvironment (TME) is challenging. In this study, a photosensitive, dual-targeting nanoparticle system (M.RGD@Cr-CTS-siYTHDF1 NPs) was developed. The structure includes a shell of DSPE-modified RGD peptides targeting integrin receptors on tumor cells and carboxymethyl mannose targeting CD206 receptors on macrophages, with a core of chitosan adsorbing m6A reading protein YTHDF1 siRNA and chromium nanoparticles (Cr NPs). The approach is specifically designed to target TAM and cancer cells, utilizing the photothermal effect of Cr NPs to disrupt the TME and deliver siYTHDF1 to TAM. In experiments with tumor-bearing mice, M.RGD@Cr-CTS-siYTHDF1 NPs, when exposed to laser irradiation, effectively killed tumor cells, disrupted the TME, delivered siYTHDF1 to TAMs, silenced the YTHDF1 gene, and shifted the STAT3-STAT1 equilibrium by reducing STAT3 and enhancing STAT1 expression. This reprogramming of TAMs towards an anti-tumor phenotype led to a pro-immunogenic TME state. The strategy also suppressed immunosuppressive IL-10 production, increased expression of immunostimulatory factors (IL-12 and IFN-γ), boosted CD8 + T cell infiltration and M1-type TAMs, and reduced Tregs and M2-type TAMs within the TME. In conclusion, the dual-targeting M.RGD@Cr-CTS-siYTHDF1 NPs, integrating dual-targeting capabilities with photothermal therapy (PTT) and RNA interference, offer a promising approach for molecular targeted cancer immunotherapy with potential for clinical application. Graphical Abstract

The present study designed and prepared a novel platinum alloy system Pt-xAu-5Ni (x = 0, 2, 5, wt.%) with high strength and good electrical resistivity. The mechanical, electrical properties and related microstructure during the cold deformation and subsequent aging process were investigated. The cold-deformed Pt–5Ni alloy obtained the yield strength of 581 MPa, the ultimate tensile strength of 828 MPa, the hardness of 283 HV, and the electrical resistivity of 23.9 μΩ⋅cm. The subsequent aging process and the Au addition into Pt–5Ni alloy were found to both enhance the mechanical properties. Therefore, with the dual strengthening effect of the subsequent aging and the Au addition, Pt–5Au–5Ni alloy achieved the high yield strength of 889 MPa, the high ultimate tensile strength of 1117 MPa, the high hardness of 361 HV with the electrical resistivity of 26.7 μΩ⋅cm. The precipitation of L12-type Pt3Ni nanoparticles and L11-type CSRO dominated the age-strengthening behavior of Pt–2Au–5Ni and Pt–5Au–5Ni alloys after cold deformation. The Au addition refined the grains via the experimental observations, and predictably favored the L12-type Pt3Ni nanoprecipitation based on the thermodynamical calculations, thus the Au addition effectively strengthened Pt–5Ni alloy. This study provides a novel platinum alloy system with excellent mechanical and electrical properties, which has potential application in the electrical contact field.

Ultrafiltration and nanofiltration membrane coupling technology was used to investigate the effects of membrane coupling technology on the concentration effect of biogas slurry and wastewater purification capacity under pH 5-9. The results showed that under the condition of VRF as 5 and 10 times, the concentration and nutrient removal effects under pH of 5-7 were better than those under alkaline condition. With pH of 7 and VRF of 10 times,the concentrations of TN,TP and TK in concentrated liquid were 1 760 mg/L, 435 mg/L and 2 100 mg/L, respectively,and the concentration times were 8.8, 7.63 and 6.34 times, which showed the best salt removal effect and concentration effect. The removal rates of NH4+-N, TN, TP and COD in the filtrate reached 89.71%, 81%, 99.82% and 95.77%, respectively. The effluent quality reached the secondary standards of Pollutant Discharge Standards for Urban Sewage Treatment Plants(GB18918—2002). According to the analysis of scanning electron microscope(SEM) and X-ray energy analyzer(EDX), the membrane pollution included organic-inorganic co-pollution. The removal of pollutants on the membrane surface could be partially achieved by acid and alkali washing.

Abstract Tumor vaccines, a crucial immunotherapy, have gained growing interest because of their unique capability to initiate precise anti-tumor immune responses and establish enduring immune memory. Injected tumor vaccines passively diffuse to the adjacent draining lymph nodes, where the residing antigen-presenting cells capture and present tumor antigens to T cells. This process represents the initial phase of the immune response to the tumor vaccines and constitutes a pivotal determinant of their effectiveness. Nevertheless, the granularity paradox, arising from the different requirements between the passive targeting delivery of tumor vaccines to lymph nodes and the uptake by antigen-presenting cells, diminishes the efficacy of lymph node-targeting tumor vaccines. This study addressed this challenge by employing a vaccine formulation with a tunable, controlled particle size. Manganese dioxide (MnO2) nanoparticles were synthesized, loaded with ovalbumin (OVA), and modified with A50 or T20 DNA single strands to obtain MnO2/OVA/A50 and MnO2/OVA/T20, respectively. Administering the vaccines sequentially, upon reaching the lymph nodes, the two vaccines converge and simultaneously aggregate into MnO2/OVA/A50-T20 particles through base pairing. This process enhances both vaccine uptake and antigen delivery. In vitro and in vivo studies demonstrated that, the combined vaccine, comprising MnO2/OVA/A50 and MnO2/OVA/T20, exhibited robust immunization effects and remarkable anti-tumor efficacy in the melanoma animal models. The strategy of controlling tumor vaccine size and consequently improving tumor antigen presentation efficiency and vaccine efficacy via the DNA base-pairing principle, provides novel concepts for the development of efficient tumor vaccines. Graphical Abstract

Abstract Background Inadequate DNA damage repair promotes aberrant differentiation of mammary epithelial cells. Mammary luminal cell fate is mainly determined by a few transcription factors including GATA3. We previously reported that GATA3 functions downstream of BRCA1 to suppress aberrant differentiation in breast cancer. How GATA3 impacts DNA damage repair preventing aberrant cell differentiation in breast cancer remains elusive. We previously demonstrated that loss of p18, a cell cycle inhibitor, in mice induces luminal-type mammary tumors, whereas depletion of either Brca1 or Gata3 in p18 null mice leads to basal-like breast cancers (BLBCs) with activation of epithelial-mesenchymal transition (EMT). We took advantage of these mutant mice to examine the role of Gata3 as well as the interaction of Gata3 and Brca1 in DNA damage repair in mammary tumorigenesis. Results Depletion of Gata3, like that of Brca1, promoted DNA damage accumulation in breast cancer cells in vitro and in basal-like breast cancers in vivo. Reconstitution of Gata3 improved DNA damage repair in Brca1-deficient mammary tumorigenesis. Overexpression of GATA3 promoted homologous recombination (HR)-mediated DNA damage repair and restored HR efficiency of BRCA1-deficient cells. Depletion of Gata3 sensitized tumor cells to PARP inhibitor (PARPi), and reconstitution of Gata3 enhanced resistance of Brca1-deficient tumor cells to PARP inhibitor. Conclusions These results demonstrate that Gata3 functions downstream of BRCA1 to promote DNA damage repair and suppress dedifferentiation in mammary tumorigenesis and progression. Our findings suggest that PARP inhibitors are effective for the treatment of GATA3-deficient BLBCs.

Ascribing to the abundance of Ti element, exceptional electrical conductivity, and electrocatalytic performance, titanium carbide MXene (Ti3C2Tx, MX) is considered as an ideal conductive matrix and employed for in situ preparation of promising TiO2 NPs@MX/reduced graphene oxide (rGO) heterojunction electrodes for uric acid (UA) detection. However, the incapability of achieving the controllable growth and synthesis of TiO2 nanoparticles (NPs) on MX nanosheets is a bottleneck in fabricating optimal and controllable TiO2 NPs@MX hybrid. Herein, an “on‐site transformation strategy” is developed to synthetize TiO2 NPs@MX/rGO heterojunction platform controllably by in situ electrochemical oxidizing MX nanosheets at various treatment times. The proposed approach allows for the greater operability to controllably grow and synthetize TiO2 NPs on the surface of MX nanosheets. The heterojunction electrodes present a linear voltammetric response toward UA in the concentration range of 0.003–0.3 and 0.3–300 μm and a low detection limit of 0.78 nm (S/N = 3). Additionally, a handheld electrochemical system with a smartphone readout is developed for point‐of‐care health monitoring, enabling fast, precise, and specific recognition of UA in real urine samples. The study provides a facile and controllable approach to fabricate TiO2 NPs@MX/rGO heterojunction platform for future use in other biomolecules' detection.

Background: Neoadjuvant therapy improves survival benefits in patients with locally advanced non-small cell lung cancer but increases tissue density, presenting challenges for surgeons. Objectives: To compare the differences in surgical complexity and short-term prognostic outcomes between neoadjuvant targeted therapy (NTT) and neoadjuvant chemoimmunotherapy (NCI). Design/methods: This study enrolled 106 patients underwent curative surgery after neoadjuvant therapy between January 2020 and December 2023 at the National Cancer Center of China. Differences in surgical complexity and short-term prognostic outcomes between the two neoadjuvant therapy cohorts were evaluated. The pathological indicators such as pathological response rate and lymph node upstaging/downstaging were then analyzed. Results: In total, 33 patients underwent NTT and 73 underwent NCI preoperatively. Patients who received NTT showed a higher minimally invasive surgery rate (84.8% versus 53.4%, p < 0.01), shorter operative time (144 versus 184 min, p < 0.01), lower conversion rate (3.3% versus 17.8%, p = 0.03), less postoperative drainage (day 3: 140 versus 200 mL, p = 0.03), and lower incidence of postoperative complications including arrhythmias (6.1% versus 26%, p = 0.02). The pathological response rate in the NTT and NCI groups was 70% and 75%, respectively, with the latter group showing a higher complete pathological response rate. The two groups had no significant differences in major pathological response and lymph node pathological response rate. Conclusion: Patients who received NTT presented fewer surgical challenges for surgeons and had better surgical outcomes than those who received NCI therapy, with comparable pathological response rates between the two cohorts. Accordingly, NTT is the preferred induction regimen for patients harboring mutation status.

ObjectiveTo explore the application effect of the online and offline mixed teaching mode in nursing practice teaching based on the Source Message Channel Receiver (SMCR) communication model.MethodsBy using the convenience sampling method, 15 nursing students who practiced their internship in the Department of Critical Care Medicine at Beijing Friendship Hospital affiliated to Capital Medical University for 4 weeks, from 1 April 2022 to 31 December 2023, were selected as the experimental group. A total of 16 nursing students who practiced in the same hospital in 2021 were selected as the control group. The control group used traditional teaching mode for teaching, and the experimental group used the online and offline teaching mode for teaching. The theoretical and practical achievements, competency, and teaching satisfaction of the two groups of nursing students were compared and analyzed after the internship.ResultsThe theoretical knowledge, operational performance, competence of the nurses, and satisfaction with the teaching in the experimental group were higher than those of the control group (P < 0.05).ConclusionBased on the SMCR communication model, exploring the online and offline mixed teaching mode plays an important role in the teaching process of nursing practice, which can not only effectively improve the comprehensive performance of nursing students but also help to improve their satisfaction with teaching and has a positive impact on the cultivation of high-quality nursing talents.

Purpose: Invasive micropapillary carcinoma (IMPC) of the breast has a high propensity for lymphovascular invasion and axillary lymph node metastasis and displays an ‘inside-out’ growth pattern, but the molecular mechanism of invasion, metastasis and cell polarity reversal in IMPC is unclear. Methods: and Patients: Cell growth curves, tumor sphere formation assays, transwell assays, mouse xenograft model and immunofluorescence were evaluated to investigate the effects of miR-30c and MTDH. Dual luciferase reporter assays was performed to confirm that the MTDH (metadherin) 3′UTR bound to miR-30c. MiRNA in situ hybridization (ISH) and immunohistochemistry (IHC) were carried out on IMPC patient tissues for miR-30c and MTDH expression, respectively. Results: We found miR-30c as a tumor suppressor gene in cell proliferation, metastasis and polarity reversal of IMPC. Overexpression of miR-30c inhibited cell growth and metastasis in vitro and in vivo. MiR-30c could directly target the MTDH 3′UTR. MiR-30c overexpression inhibited breast cancer cell proliferation, invasion and metastasis by targeting MTDH. Moreover, miR-30c/MTDH axis could also regulate cell polarity reversal of IMPC. By ISH and IHC analyses, miR-30c and MTDH were significantly correlated with tumor size, lymph nodule status and tumor grade, the ‘inside-out’ growth pattern, overall survival (OS) and disease-free survival (DFS) in IMPC patients. Conclusions: Overall, miR-30c/MTDH axis was responsible for tumor proliferation, metastasis and polarity reversal. It may provide promising therapeutic targets and prognostic biomarkers for patients with IMPC.

In this paper, we prepared and investigated the electrical switching behaviors of Cu3P/Ag2S heterojunction in the absence/presence of light/heat excitation. The structure exhibited bipolar memristor characteristics. The resistive switching mechanism is due to the formation of Ag conductive filaments and phase transition in Cu3P. We found that the resistance ratio (ROFF/RON) increased by a factor of 1.4/1.8 after light/heat excitation. The underlying mechanism was due to the photoelectric effect/Seebeck effect. Our results are helpful for the understanding of the resistive switching performance of Cu3P/Ag2S junctions, providing valuable insights into the factors influencing resistive switching performance and a clue for the enhancement of the memristor performance.

Abstract Non-alcoholic fatty liver disease (NAFLD) has emerged as one of the major causes of liver-related morbidity and mortality globally. It ranges from simple steatosis to non-alcoholic steatohepatitis (NASH) characterized by ballooning and hepatic inflammation. In the past few years, pyroptosis has been shown as a type of programmed cell death that triggers inflammation and plays a role in the development of NASH. However, the roles of pyroptosis-related genes (PRGs) in NASH remained unclear. In this study, we studied the expression level of pyroptosis-related genes (PRGs) in NASH and healthy controls, developed a diagnostic model of NASH based on PRGs and explored the pathological mechanisms associated with pyroptosis. We further compared immune status between NASH and healthy controls, analyzed immune status in different subtypes of NASH. We identified altogether twenty PRGs that were differentially expressed between NASH and normal liver tissues. Then, a novel diagnostic model consisting of seven PRGs including CASP3, ELANE, GZMA, CASP4, CASP9, IL6 and TP63 for NASH was constructed with an area under the ROC curve (AUC) of 0.978 (CI 0.965–0.99). Obvious variations in immune status between healthy controls and NASH cases were detected. Subsequently, the consensus clustering method based on differentially expressed PRGs was constructed to divide all NASH cases into two distinct pyroptosis subtypes with different immune and biological characteristics. Pyroptosis-related genes may play an important role in NASH and can provide new insights into the diagnosis and underlying mechanisms of NASH.

In the chip encapsulation process, internal defects arise due to both natural and anthropogenic factors, primarily manifesting as a diverse array of missing Gold Wires and Solder Joints. Accurate delineation of these Gold Wires and Solder Joints through a mask is essential for defect analysis. Notably, Gold Wires exhibit a large spatial scale, while Solder Joints have a smaller scale; both possess intricate textures. Although Transformer methods can effectively model relationships between distant pixels, they tend to lose fine-grained texture information. Conversely, CNN methods excel in learning local information but may compromise spatial relationships between targets. Consequently, utilizing either of these methods alone presents limitations. In addressing this issue, we propose the Global-Local Feature Multilevel Fusion Network architecture—SegCAF, which combines the strengths of CNN and Transformer. Our research introduces a dual-branch interactive parallel network, where the CNN branch extracts local information, and the Transformer branch captures global dependencies. Subsequently, a feature fusion module aligns and aggregates the encoded features from both branches, leveraging both global context and local details. Furthermore, an auxiliary segmentation head is added to the Transformer branch to enhance training efficiency and reinforce information interaction between the two branches. In the experimental phase, we collected and annotated a dataset of X-ray images depicting internal defects in industrially produced chipsets. We conducted feature visualization analysis and model performance evaluations on this dataset. The results demonstrate that the proposed SegCAF model significantly outperforms existing mainstream models, achieving an mIoU of $90.56\%$ and an mPA of $81.17\%$ . This indicates that SegCAF effectively addresses the challenge of precise segmentation of chip defects using both local and global information in network design and optimization. Consequently, it enhances the quality of relevant electronic products and improves production inspection efficiency.

This study presents a novel method to assess the learning effectiveness using Electroencephalography (EEG)-based deep learning model. It is difficult to assess the learning effectiveness of professional courses in cultivating students’ ability objectively by questionnaire or other assessment methods. Research in the field of brain has shown that innovation ability can be reflected from cognitive ability which can be embodied by EEG signal features. Three navigation tasks of increasing cognitive difficulty were designed and a total of 41 subjects participated in the experiment. For the classification and tracking of the subjects’ EEG signals, a convolutional neural network (CNN)-based Multi-Time Scale Spatiotemporal Compound Model (MTSC) is proposed in this paper to extract and classify the features of the subjects’ EEG signals. Furthermore, Spiking neural networks (SNN) -based NeuCube is used to assess the learning effectiveness and demonstrate cognitive processes, acknowledging that NeuCube is an excellent method to display the spatiotemporal differences between spikes emitted by neurons. The results of the classification experiment show that the cognitive training traces of different students in solving three navigational problems can be effectively distinguished. More importantly, new information about navigation is revealed through the analysis of feature vector visualization and model dynamics. This work provides a foundation for future research on cognitive navigation and the training of students’ navigational skills.

Diabetic wounds pose a clinical challenge due to persistent inflammation, severe bacterial infections, inadequate vascularization, and pronounced oxidative stress. Current therapeutic modalities fail to provide satisfactory outcomes in managing these conditions, resulting in considerable patient distress. Two-dimensional nanomaterials (2DNMs), characterized by their unique nanosheet structures, expansive surface areas, and remarkable physicochemical properties, have garnered considerable attention for their potential in therapeutic applications. Emerging 2DNMs can be loaded with various pharmacological agents, including small molecules, metal ions, and liposomes. Moreover, they can be integrated with various biomaterials such as hydrogels, microneedles, and microspheres, thus demonstrating unprecedented advantages in expediting the healing process of diabetic wounds. Moreover, 2DNMs exhibit exceptional performance characteristics, including high biocompatibility, effective antimicrobial properties, optimal phototherapeutic effects, and enhanced electrostimulation capabilities. These properties enable them to modulate the wound microenvironment, leading to widespread application in tissue repair with remarkable outcomes. This review delineates several emerging 2DNMs, such as graphene and its derivatives, black phosphorus, MXenes, and transition metal dichalcogenides, in the context of diabetic wound repair. Furthermore, it elucidates the translational challenges and future perspectives of 2DNMs in wound healing treatments. Overall, 2DNMs present a highly promising strategy for ameliorating diabetic wounds, thus providing novel avenues for diagnostic and therapeutic strategies in diabetic wound management.

Silk fibroin (SF), which is extensively utilized in tissue engineering and vascular grafts for enhancing vascular regeneration, has not been thoroughly investigated for its epigenetic effects on endothelial cells (EC). This study employed RNA sequencing analysis to evaluate the activation of histone modification regulatory genes in EC treated with SF. Subsequent investigations revealed elevated H3K9me3 levels in SF-treated EC, as evidenced by immunofluorescence and western blot analysis. The study utilized H2B-eGFP endothelial cells to demonstrate that SF treatment results in the accumulation of H2B-marked chromatin in the nuclear inner cavities of EC. Inhibition of H3K9me3 levels by a histone deacetylase inhibitor TSA decreased cell proliferation. Furthermore, the activation of the MAPK signaling pathway using chromium picolinate decreased the proliferative activity and H3K9me3 level in SF-treated EC. SF also appeared to enhance cell growth and proliferation by modulating the H3K9me3 level and reorganizing chromatin, particularly after oxidative stress induced by H2O2 treatment. In summary, these findings indicate that SF promotes EC proliferation by increasing the H3K9me3 level even under stress conditions.

At present, it is widely believed that a 95–96% average nucleotide identity (ANI) value is equivalent to a 70% digital DNA–DNA hybridization (dDDH) value in the prokaryotic taxonomy. However, in the present study, comparative genome analysis of 29 pairs of Amycolatopsis type strains revealed that a 70% dDDH value did not correspond to a 95–96% ANI based on the MuMmer ultra-rapid aligning tool (ANIm) but approximately corresponded to a 96.6% ANIm value in the genus Amycolatopsis. Based on this corresponding relationship, phenotypic and chemotaxonomical characteristics, as well as phylogenetic analysis, an actinobacterial strain HUAS 11-8T isolated from the rhizosphere soil of Cynara scolymus, was subjected to a polyphasic taxonomic characterization. Based on EzBioCloud alignment, it was found that strain HUAS11-8T had the 16S rRNA gene similarities of 99.78% with A. rhizosphaerae JCM 32589T, 97.8% with A. dongchuanensis YIM 75904T, and

Focusing on the situation of the low helium content in natural gas resource in China and the high cost of helium extraction, the OPEX prediction model of helium extraction that based on the Response Surface Methodology (RSM) is proposed. This method applies ASPEN-HYSYS software to simulate the helium extraction process flow for a given product composition, pressure, and temperature; Applying the Design Expert module for Response Surface Methodology(RSM) parameter design, combined with OPEX of existing projects, determine the key influencing factors and upper and lower limits of OPEX, and obtaining the corresponding OPEX for different parameter values; Applying the Box Behnken Design (BBD) principle to optimize the helium extraction process parameters of RSM, based on fitting results and parameter significance verification of second-order regression function, the OPEX prediction model is built.This method is applied to a domestic helium extraction project, and the unit helium extraction cost is between 100 and 119.52 yuan/m3, IRR is 13.37%. The result shows the project has economic benefit, and the method presents a good perspective application.

In this paper, we study the bifurcation of limit cycles from a class of cubic integrable non-Hamiltonian systems under arbitrarily small piecewise smooth perturbations of degree $n$. By using the averaging theory and complex method, the lower and upper bounds for the maximum number of limit cycles bifurcating from the period annulus of the unperturbed systems are given at first order in $\varepsilon$. It is also shown that in this case, the maximum number of limit cycles produced by piecewise smooth perturbations is almost twice the upper bound of the maximum number of limit cycles produced by smooth perturbations for the considered systems.

Microstructure evolution and coarsening behavior of precipitated O phase were systematically investigated in this study, and the corresponding microstructures were characterized by scanning electron microscopy and transmission electron microscopy. The results showed that the original microstructure was composed of lath O phase, α2 phase and B2 matrix. The precipitated O phase presented different morphologies and sizes during heat treatment. With the increase of solution temperature and holding time, the O phase occurred coarsening, with a thickness ranging from 0.73 increased to 2.64 μm. But the volume fraction decreased from 57.65 to 18.40 %. During aging treatment, large amounts of fine secondary acicular O phase have precipitated from the matrix. As the aging temperature increases, the O phase underwent coarsening and the thickness increases from 0.70 to 1.40 μm. However, the aging temperature has little effect on the precipitation of acicular O phase, and the volume fraction decreases from 37.66 to 33.32 %. Research found that the small-sized O phase gradually dissolved in the matrix, while the large-sized O phase grew. This phenomenon can be explained by Ostwald ripening mechanism. The TEM analysis revealed that the O phase occurred separation, mainly due to the diffusion of solute atoms and the embedding of B2 matrix. Meanwhile, the O phase had been completed and segmented. The coarsening mechanism of the O phase was also explained by the boundary splitting mechanism and terminal migration mechanism.

Abstract Background The epididymis is crucial for post-testicular sperm development which is termed sperm maturation. During this process, fertilizing ability is acquired through the epididymis-sperm communication via exchange of protein and small non-coding RNAs (sncRNAs). More importantly, epididymal-derived exosomes secreted by the epididymal epithelial cells transfer sncRNAs into maturing sperm. These sncRNAs could mediate intergenerational inheritance which further influences the health of their offspring. Recently, the linkage and mechanism involved in regulating sperm function and sncRNAs during epididymal sperm maturation are increasingly gaining more and more attention. Methods An epididymal-specific ribonuclease T2 (RNase T2) knock-in (KI) mouse model was constructed to investigate its role in developing sperm fertilizing capability. The sperm parameters of RNase T2 KI males were evaluated and the metabolic phenotypes of their offspring were characterized. Pandora sequencing technology profiled and sequenced the sperm sncRNA expression pattern to determine the effect of epididymal RNase T2 on the expression levels of sperm sncRNAs. Furthermore, the expression levels of RNase T2 in the epididymal epithelial cells in response to environmental stress were confirmed both in vitro and in vivo. Results Overexpression of RNase T2 caused severe subfertility associated with astheno-teratozoospermia in mice caput epididymis, and furthermore contributed to the acquired metabolic disorders in the offspring, including hyperglycemia, hyperlipidemia, and hyperinsulinemia. Pandora sequencing showed altered profiles of sncRNAs especially rRNA-derived small RNAs (rsRNAs) and tRNA-derived small RNAs (tsRNAs) in RNase T2 KI sperm compared to control sperm. Moreover, environmental stress upregulated RNase T2 in the caput epididymis. Conclusions The importance was demonstrated of epididymal RNase T2 in inducing sperm maturation and intergenerational inheritance. Overexpressed RNase T2 in the caput epididymis leads to astheno-teratozoospermia and metabolic disorder in the offspring.

Abstract Background Progression of Alzheimer’s disease leads to synapse loss, neural network dysfunction and cognitive failure. Accumulation of protein aggregates and brain immune activation have triggering roles in synaptic failure but the neuronal mechanisms underlying synapse loss are unclear. On the neuronal surface, cellular prion protein (PrPC) is known to be a high-affinity binding site for Amyloid-β oligomers (Aβo). However, PrPC’s dependence in knock-in AD models for tau accumulation, transcriptomic alterations and imaging biomarkers is unknown. Methods The necessity of PrPC was examined as a function of age in homozygous App NL−G−F /hMapt double knock-in mice (DKI). Phenotypes of App NL−G−F /hMapt mice with a deletion of Prnp expression (DKI; Prnp −/− ) were compared with DKI mice with intact Prnp, mice with a targeted deletion of Prnp (Prnp −/− ), and mice with intact Prnp (WT). Phenotypes examined included behavioral deficits, synapse loss by PET imaging, synapse loss by immunohistology, tau pathology, gliosis, inflammatory markers, and snRNA-seq transcriptomic profiling. Results By 9 months age, DKI mice showed learning and memory impairment, but DKI; Prnp −/− and Prnp −/− groups were indistinguishable from WT. Synapse loss in DKI brain, measured by [18F]SynVesT-1 SV2A PET or anti-SV2A immunohistology, was prevented by Prnp deletion. Accumulation of Tau phosphorylated at aa 217 and 202/205, C1q tagging of synapses, and dystrophic neurites were all increased in DKI mice but each decreased to WT levels with Prnp deletion. In contrast, astrogliosis, microgliosis and Aβ levels were unchanged between DKI and DKI; Prnp −/− groups. Single-nuclei transcriptomics revealed differential expression in neurons and glia of DKI mice relative to WT. For DKI; Prnp −/− mice, the majority of neuronal genes differentially expressed in DKI mice were no longer significantly altered relative to WT, but most glial DKI-dependent gene expression changes persisted. The DKI-dependent neuronal genes corrected by Prnp deletion associated bioinformatically with synaptic function. Additional genes were uniquely altered only in the Prnp −/− or the DKI; Prnp −/− groups. Conclusions Thus, PrPC-dependent synapse loss, phospho-tau accumulation and neuronal gene expression in AD mice can be reversed without clearing Aβ plaque or preventing gliotic reaction. This supports targeting the Aβo-PrPC interaction to prevent Aβo-neurotoxicity and pathologic tau accumulation in AD.

Gut dysbiosis is associated with several pathological processes. Previous study showed that regular exercise can protect against dysmetabolism in high-fat diet (HFD) fed mice through butyrate-SESN2 pathway, and SESN2 ablation weakened the protective effects of exercise. Here, we investigated whether SESN2-deficiency suppresses the exercise response to microbiota composition and subsequently reduces the benefits of exercise on dysmetabolism induced by HFD. Wild type (WT) and SESN2−/− mice were assigned to five-groups, fed with either normal chow or HFD and with or without exercise training for 15-week. Fecal microbiota composition and function were assessed by 16S rRNA sequencing. The sequencing results showed that SESN2−/− mice displayed differed microbiome profile from WT mice. Exercise enriched the microflora diversity and increased the beneficial microbial species in WT mice, and SESN2 ablation weakened the beneficial effects of exercise on microbial resilience following HFD consumption. Moreover, network analysis revealed that exercise increased correlation density and clustering of operational taxonomic units in WT mice only. KEGG demonstrated that some dominant metabolism-related enzymes and modules increased in SESN2−/− mice. Our results indicated that the effects of exercise on metabolism are associated with the perturbations of gut microbiota composition and function, suggesting that SESN2 contributes to maintain metabolic homeostasis.−

This study investigated the effects of nano zero-valent iron-modified biochar (nZVI@BC) as a soil amendment on potted rice growth, soil properties, and heavy metal dynamics. Seven treatments with varying amounts of soil conditioner, biochar, and nZVI@BC were applied to potted rice. Results showed that nZVI@BC application significantly improved rice agronomic traits, with the 15 g·kg−1 treatment increasing the panicle formation rate by 15% and 100-grain weight by 8% compared to the control. Soil fertility was enhanced, with available phosphorus increasing from 137 to 281 mg·kg−1 in the most effective treatment. Heavy metal analysis revealed that nZVI@BC application did not increase soil heavy metal content, with Cd levels remaining below 0.3 mg·kg−1 across treatments. Notably, the 10 g·kg−1 nZVI@BC treatment showed potential for slight Cd immobilization, reducing its concentration from 0.32 to 0.26 mg·kg−1. Microbial community analysis showed that nZVI@BC altered soil microbial diversity and composition, with the 10 g·kg−1 treatment resulting in the highest fungal diversity (Chao1 index: 294.219). The relative abundance of the beneficial fungal class Agaricomycetes increased from 40% to 55% with optimal nZVI@BC application. These findings suggest that nZVI@BC has potential as an effective soil amendment for improving rice cultivation while maintaining soil health, microbial diversity, and potentially mitigating heavy metal contamination.

Oxalic acid (OA) is a predominant constituent in kidney stones, contributing to 70–80% of all cases. Rapid detection of OA is vital for the early diagnosis and treatment of kidney stone conditions. This work introduces a novel electrochemical sensing approach for OA, leveraging vanadium disulfide (VS2) nanoflowers synthesized via hydrothermal synthesis. These VS2 nanoflowers, known for their excellent electrocatalytic properties and large surface area, are used to modify glassy carbon electrodes for enhanced OA sensing. The proposed OA sensor exhibits high sensitivity and selectivity across a wide linear detection range of 0.2–20 μM, with an impressively low detection limit of 0.188 μM. The practicality of this sensor was validated through interference studies, offering a promising tool for the early diagnosis and monitoring of kidney stone diseases.

This review critically examines the progress and challenges in the field of nanostructured tungsten oxide (WO3) gas sensors. It delves into the significant advancements achieved through nanostructuring and composite formation of WO3, which have markedly improved sensor sensitivity for gases like NO2, NH3, and VOCs, achieving detection limits in the ppb range. The review systematically explores various innovative approaches, such as doping WO3 with transition metals, creating heterojunctions with materials like CuO and graphene, and employing machine learning models to optimize sensor configurations. The challenges facing WO3 sensors are also thoroughly examined. Key issues include cross-sensitivity to different gases, particularly at higher temperatures, and long-term stability affected by factors like grain growth and volatility of dopants. The review assesses potential solutions to these challenges, including statistical analysis of sensor arrays, surface functionalization, and the use of novel nanostructures for enhanced performance and selectivity. In addition, the review discusses the impact of ambient humidity on sensor performance and the current strategies to mitigate it, such as composite materials with humidity shielding effects and surface functionalization with hydrophobic groups. The need for high operating temperatures, leading to higher power consumption, is also addressed, along with possible solutions like the use of advanced materials and new transduction principles to lower temperature requirements. The review concludes by highlighting the necessity for a multidisciplinary approach in future research. This approach should combine materials synthesis, device engineering, and data science to develop the next generation of WO3 sensors with enhanced sensitivity, ultrafast response rates, and improved portability. The integration of machine learning and IoT connectivity is posited as a key driver for new applications in areas like personal exposure monitoring, wearable diagnostics, and smart city networks, underlining WO3's potential as a robust gas sensing material in future technological advancements.

Strengthening columns holds a crucial role in structural engineering and is frequently called for due to a range of factors, including heightened load requirements, structural degradation, design flaws, or the need for seismic retrofitting. Natural Fiber-Reinforced Polymers (NFRP) in concrete reinforcement has gained significant attention in recent years as a sustainable and eco-friendly alternative to strengthened reinforced concrete. NFRP jacketing presents an adaptable option, as it delivers an improved load-carrying capability as a confining effect. This paper explores the fundamental reasons behind the need for column strengthening and the advantages of employing NFRP jacketing as a preferred method. The study examined the influence of varying fiber densities and the number of fiber layers in NFRP on the mechanical properties of concrete, with a specific focus on its confined concrete compressive strength. The test specimen was a cylinder with a diameter of 150mm and a height of 300mm. NFRP, made from abaca fiber and resin, was attached around the specimen’s circumference to provide a confinement effect. Axial load was applied to the test specimen. The findings indicated that introducing abaca fiber as an NFRP material increased confined concrete compressive strength by up to 37% compared to unconfined concrete. Moreover, the application of three layers of NFRP fibers results in a 15% rise in confined concrete stress, especially when higher-density fiber types are utilized. Study findings suggest that natural fiber density and the number of layers play a role in enhancing concrete strength, however, their influence may not be significantly pronounced.

ObjectiveThe relationships between circulating inflammatory proteins and COVID-19 have been observed in previous cohorts. However, it is not unclear which circulating inflammatory proteins may boost the risk of or protect against COVID-19.MethodsWe performed Mendelian randomization (MR) analysis using GWAS summary result of 91 circulating inflammation-related proteins (N = 14,824) to assess their causal impact on severe COVID-19. The COVID-19 phenotypes encompassed both hospitalized (N = 2,095,324) and critical COVID-19 (N = 1,086,211). Moreover, sensitivity analyses were conducted to evaluate the robustness and reliability.ResultsWe found that seven circulating inflammatory proteins confer positive causal effects on severe COVID-19. Among them, serum levels of IL-10RB, FGF-19, and CCL-2 positively contributed to both hospitalized and critical COVID-19 conditions (OR: 1.10~1.16), while the other 4 proteins conferred risk on critical COVID-19 only (OR: 1.07~1.16), including EIF4EBP1, IL-7, NTF3, and LIF. Meanwhile, five proteins exert protective effects against hospitalization and progression to critical COVID-19 (OR: 0.85~0.95), including CXCL11, CDCP1, CCL4/MIP, IFNG, and LIFR. Sensitivity analyses did not support the presence of heterogeneity in the majority of MR analyses.ConclusionsOur study revealed risk and protective inflammatory proteins for severe COVID-19, which may have vital implications for the treatment of the disease.

A new biphase tandem redox electrolyte system is designed by immobilizing imidazolium iodide on Co, N‐doped carbon electrode in conjunction with polysulfide redox mediator in aqueous solution. Due to its biphasic feature, this redox system is enabled to separate the redox reactions in different phases, and hence, prevent the intertwined problem of redox reactions that occurred in one‐phase tandem redox system. Investigations show that the biphase redox system can efficiently accelerate electron reduction, and thereby inhibit charge recombination. Consequently, quantum dot (QD)‐sensitized solar cell fabricates using this biphase tandem redox together with CdSe QD‐sensitized photoanode achieved a high cell efficiency of 6.85% at 100 mW cm2 simulated AM 1.5, showing about 33% increment as compared to the traditional pure polysulfide‐based device (5.14%). The encouraging results indicate that the utilization of biphase tandem electrolytes can be an efficient way to improve the performance of sensitized solar cells.

Background: Epidemiological evidence on the association of PM2.5 (particulate matter with aerodynamic diameter ≤ 2.5 μm) and its specific components with hypertension and blood pressure is limited. Methods: We applied information of participants from the World Health Organization's (WHO) Study on Global Ageing and Adult Health (SAGE) to estimate the associations of long-term PM2.5 mass and its chemical components exposure with blood pressure (BP) and hypertension incidence in Chinese adults ≥ 50 years during 2007–2018. Generalized linear mixed model and Cox proportional hazard model were applied to investigate the effects of PM2.5 mass and its chemical components on the incidence of hypertension and BP, respectively. Results: Each interquartile range (IQR = 16.80 μg/m3) increase in the one-year average of PM2.5 mass concentration was associated with a 17 % increase in the risk of hypertension (HR = 1.17, 95 % CI: 1.10, 1.24), and the population attributable fraction (PAF) was 23.44 % (95 % CI: 14.69 %, 31.55 %). Each IQR μg/m3 increase in PM2.5 exposure was also related to increases of systolic blood pressure (SBP) by 2.54 mmHg (95 % CI:1.99, 3.10), and of diastolic blood pressure (DBP) by 1.36 mmHg (95 % CI: 1.04, 1.68). Additionally, the chemical components of SO42−, NO3−, NH4+, OM, and BC were also positively associated with an increased risk of hypertension incidence and elevated blood pressure. Conclusions: These results indicate that long-term exposure to PM2.5 mass and its specific components may be major drivers of escalation in hypertension diseases.

Introduction: Autophagy is an important mechanism of cell homeostasis maintenance. As essential serine/threonine-protein kinases, casein kinase I family members affect tumorigenesis by regulating a variety of cellular progression. However, the mechanism by which they regulate autophagy remains unclear. Materials and methods: We silenced CK1δ/ε in cancer cells and observed cell morphology, the expression of autophagy-related genes, and its impact on cancer cell growth and viability. By inhibiting CK1δ/ε-induced upregulation of autophagy genes, we profiled the regulatory mechanism of CK1δ/ε on autophagy and cancer cell growth. The impact of CK1δ/ε inhibition on tumor cell growth was also assessed in vivo. Results: Here, we found that CK1δ/ε played an important role in ULK1-mediated autophagy regulation in both lung cancer and melanoma cells. Mechanically, silencing CK1δ/ε increased ULK1 expression with enhanced autophagic flux and suppressed cancer cell proliferation, while ULK1 knockdown blocked the activation of autophagy caused by CK1δ/ε inhibition. By silencing CK1δ/ε in syngeneic mouse model bearing LLC1 murine lung cancer cells in vivo, we observed tumor growth suppression mediated by CK1δ/ε inhibition. Conclusion: Our results provide evidence for the role of CK1δ/ε in the regulation of tumorigenesis via the ULK1-mediated autophagy, and also suggest the impact of CK1δ/ε inhibition on tumor growth and its significance as a potential therapeutic target.

BackgroundCivil aviation pilots are actual operators of civil aircraft. Their job operations are directly associated with passenger safety and flight safety. Unsafe aviation operations are related to fatigue caused by poor sleep quality. Recently, with the promotion of China's air transportation business, irregular working hours of civil aviation pilots rise gradually. However, there is still a lack of relevant research on the influence of working conditions on sleep quality in this group.ObjectiveTo explore potential impact factors of sleep quality among civil aviation pilots, for the purposes of improving sleep quality and health level of this group and ensuring aviation flight safety by formulating health management suggestions in a targeted manner.MethodsAll pilots of an aviation company were approached when they visited the Shanghai Hospital of Civil Aviation Administration of China for their health examinations. After informed consent, an online questionnaire survey was conducted. Self-made questionnaires were used to collect information on general conditions, lifestyle, and subjective work stress levels. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. A total of 1204 valid questionnaires were recovered. Statistical analysis was conducted using SPSS 26.0 software.ResultsThere were 410 pilots (16.8%) who reported sleep disorders, including insufficient sleep time, difficulty falling asleep, and poor sleep quality, and 894 pilots (74.3%) who reported moderate to severe work stress. Associations were identified between sleep quality of pilots and work stress or lifestyle indicators (P

Based on the rockery photos of 10 classical gardens including world cultural heritage, this paper incorporates the combined analysis and comparison of constituent elements (rockeries, buildings and plants) of scenic surfaces, and probes into the fractal characteristics of landscaping through the theory and the fractal dimension (FD) value analysis software. Studies have shown that the quantitative evaluation data of visual complexity (FD, i.e., fractal dimension) can characterize the contour morphology of constituent elements of the scenic surface of rockeries. The relevant analysis results are as follows: (1) FD can directly quantify the morphological contour of each element. Through the statistical analysis, it can effectively avoid the misjudgment of empirical cognition and subjective feeling. Therefore, FD value can be used as one of the effective indexes to evaluate the complexity and diversity of rockery and landscape elements. (2) The change in the level of the FD value enables the intuitive analysis of the effects of the plant varieties and landscaping techniques on rockery morphological complexity. (3) Higher FD value is not always better. Necessary morphological maintenance is required to avoid excessive FD value of plants.

Abstract Urbanization is inevitable in both developing and developed countries. However, this growth and transformation of the urban area can pose a significant threat to urban cultural heritage, which is a sensitive component of the urban environment. As cities modernize and change, a risk of irreparable loss of cultural heritage exists. Therefore, taking steps to protect and preserve these sites for posterity is crucial. To better protect urban cultural heritage, decision-makers must rapidly assess the impact of urbanization on cultural heritage while maintaining a balance between cultural heritage preservation and urban growth. This study developed a risk-based cumulative impact assessment (CIA) method that integrates a set of quantifiable indicators to address these issues. This method generates standardized assessment results based on game theory and set pair analysis theory. In contrast to other CIA methods, this risk-based approach effectively manages scientific complexity and uncertainties, thus enhancing the quality of the assessment results. This method was applied to 21 classical gardens in Suzhou, China. The results show that Suzhou classical gardens are impacted by urbanization. This study confirmed that adopting a risk-based CIA method that considers the impact of adverse urbanization on cultural heritage sites is an efficient approach. Successful implementation of the proposed method can provide decision-making support for different types of cultural heritage in other areas.

Abstract Gastric cancer (GC) is notoriously resistant to current therapies due to tumor heterogeneity. Cancer stem cells (CSCs) possess infinite self-renewal potential and contribute to the inherent heterogeneity of GC. Despite its crucial role in chemoresistance, the mechanism of stemness maintenance of gastric cancer stem cells (GCSCs) remains largely unknown. Here, we present evidence that lengsin, lens protein with glutamine synthetase domain (LGSN), a vital cell fate determinant, is overexpressed in GCSCs and is highly correlated with malignant progression and poor survival in GC patients. Ectopic overexpression of LGSN in GCSC-derived differentiated cells facilitated their dedifferentiation and treatment resistance by interacting with vimentin and inducing an epithelial-to-mesenchymal transition. Notably, genetic interference of LGSN effectively suppressed tumor formation by inhibiting GCSC stemness maintenance and provoking gasdermin-D-mediated pyroptosis through vimentin degradation/NLRP3 signaling. Depletion of LGSN combined with the chemo-drugs 5-fluorouracil and oxaliplatin could offer a unique and promising approach to synergistically rendering this deadly cancer eradicable in vivo. Our data place focus on the role of LGSN in GCSC regeneration and emphasize the critical importance of pyroptosis in battling GCSC.

Ultra-high-temperature ceramics (UHTCs) are materials capable of withstanding temperatures above 2000 °C while maintaining exceptional properties, making them ideal for aerospace, automotive, and energy applications. However, they face challenges such as brittleness and limited oxidation resistance. This review highlights the potential benefits of modifying UHTCs with graphene, a material known for its excellent mechanical, thermal, and electrical properties. Incorporating graphene into UHTCs can enhance their mechanical properties, improve the oxidation resistance, increase the thermal conductivity, and tailor the electrical properties, while also improving the processability. By addressing the inherent limitations of UHTCs and enhancing their properties, graphene-modified UHTCs show promise for a wide range of high-temperature applications. The review covers recent research achievements in graphene/UHTCs composites, focusing on the synthesis methods, microstructures, macroscopic mechanical properties, oxidation resistance, thermal shock resistance, and the underlying mechanisms.

Abstract Background Accurate prediction of lymph node metastasis (LNM) is critical for selecting optimal surgical procedures in early‐stage lung adenocarcinoma (LUAD). This study aimed to develop nomograms for intraoperative prediction of LNM in clinical stage IA LUAD. Methods A total of 1227 patients with clinical stage IA LUADs on computed tomography (CT) were enrolled to construct and validate nomograms for predicting LNM (LNM nomogram) and mediastinal LNM (LNM‐N2 nomogram). Recurrence‐free survival (RFS) and overall survival (OS) were compared between limited mediastinal lymphadenectomy (LML) and systematic mediastinal lymphadenectomy (SML) in the high‐ and low‐risk groups for LNM‐N2, respectively. Results Three variables were incorporated into the LNM nomogram and the LNM‐N2 nomogram, including preoperative serum carcinoembryonic antigen (CEA) level, CT appearance, and tumor size. The LNM nomogram showed good discriminatory performance, with C‐indexes of 0.879 (95% CI, 0.847–0.911) and 0.880 (95% CI, 0.834–0.926) in the development and validation cohorts, respectively. The C‐indexes of the LNM‐N2 nomogram were 0.812 (95% CI, 0.766–0.858) and 0.822 (95% CI, 0.762–0.882) in the development and validation cohorts, respectively. LML and SML had similar survival outcomes among patients with low risk of LNM‐N2 (5‐year RFS, 88.1% vs. 89.5%, Pp = 0.790; 5‐year OS, 96.0% vs. 93.0%, p = 0.370). However, for patients with high risk of LNM‐N2, LML was associated with worse survival (5‐year RFS, 64.0% vs. 77.4%, p = 0.036; 5‐year OS, 66.0% vs. 85.9%, p = 0.038). Conclusions We developed and validated nomograms to predict LNM and LNM‐N2 intraoperatively in patients with clinical stage IA LUAD on CT. These nomograms may help surgeons to select optimal surgical procedures.

Abstract Uveal melanoma arises from stromal melanocytes and is the most prevalent primary intraocular tumor in adults. It poses a significant diagnostic and therapeutic challenge due to its high malignancy and early onset of metastases. In recent years, there has been a growing interest in the role of diverse immune cells in tumor cell development and metastasis. Using The Cancer Genome Atlas and the gene expression omnibus databases, and the CIBERSORT method, we investigated the topography of intra-tumor immune infiltration in uveal melanoma in this research. We evaluated the prognosis of uveal melanoma patients using the M2 macrophage immune cell infiltration score in conjunction with clinical tumor patient data. We built a prognostic model based on the distinctive genes of M2 macrophages and combined it with patients’ clinical data in the database; we ran a survival prognostic analysis to authenticate the model’s accuracy. The functional study revealed the importance of macrophage-associated genes in the development of uveal melanoma. Moreover, the reliability of our prediction model was verified by combining tumor mutational load, immune checkpoint, and drug sensitivity, respectively. Our study provides a reference for the follow-up study of uveal melanoma.

Epidural and subdural hematomas are commonly associated with traumatic brain injury. While surgical removal is the primary intervention for these hematomas, it is also critical to prevent and reduce complications such as post-traumatic epilepsy, which may result from inflammatory responses in the injured brain areas. In the present study, we observed that high mobility group box-1 (HMGB1) decreased in the injured brain area beneath the epidural hematoma (EDH) in rats, concurrent with elevated plasma levels of HMGB1. Anti-HMGB1 monoclonal antibody therapy strongly inhibited both HMGB1 release and the subsequent increase in plasma levels. Moreover, this treatment suppressed the up-regulation of inflammatory cytokines and related molecules such as interleukin-1-beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and inducible nitric oxide synthase (iNOS) in the injured areas. Our in vitro experiments using SH-SY5Y demonstrated that hematoma components—thrombin, heme, and ferrous ion— prompted HMGB1 translocation from the nuclei to the cytoplasm, a process inhibited by the addition of the anti-HMGB1 mAb. These findings suggest that anti-HMGB1 mAb treatment not only inhibits HMGB1 translocation but also curtails inflammation in injured areas, thereby protecting the neural tissue. Thus, anti-HMGB1 mAb therapy could serve as a complementary therapy for an EDH before/after surgery.

Recent advancements in polymer-assisted layer-by-layer (LbL) fabrication have revolutionized the development of wearable sensors for health monitoring. LbL self-assembly has emerged as a powerful and versatile technique for creating conformal, flexible, and multi-functional films on various substrates, making it particularly suitable for fabricating wearable sensors. The incorporation of polymers, both natural and synthetic, has played a crucial role in enhancing the performance, stability, and biocompatibility of these sensors. This review provides a comprehensive overview of the principles of LbL self-assembly, the role of polymers in sensor fabrication, and the various types of LbL-fabricated wearable sensors for physical, chemical, and biological sensing. The applications of these sensors in continuous health monitoring, disease diagnosis, and management are discussed in detail, highlighting their potential to revolutionize personalized healthcare. Despite significant progress, challenges related to long-term stability, biocompatibility, data acquisition, and large-scale manufacturing are still to be addressed, providing insights into future research directions. With continued advancements in polymer-assisted LbL fabrication and related fields, wearable sensors are poised to improve the quality of life for individuals worldwide.

Objective: We aimed to evaluate bidirectional genetic relationships between posttraumatic stress disorder (PTSD) and COVID-19. Methods: We investigated potential causal associations between PTSD and two COVID-19 conditions (COVID-19 hospitalization and SARS-CoV-2 infection) via Mendelian randomization (MR) analyses. Three genome-wide association study (GWAS) summary datasets were used in the study, including PTSD (N = 174,659), SARS-CoV-2 infection (N = 2,597,856), and COVID-19 hospitalization (N = 2,095,324). We performed a literature-based analysis to uncover molecular pathways connecting PTSD and COVID-19. Results: We found that PTSD exerts a causal effect on SARS-CoV-2 infection (odds ratio (OR): 1.10, 95% confidence interval (CI): 1.00–1.21, p = 0.048) and hospitalized COVID-19 (OR: 1.34, 95% CI: 1.07–1.67, p = 0.001). However, both SARS-CoV-2 infection and hospitalized COVID-19 were not associated with the risk of PTSD. Pathway analysis revealed that several immunity-related genes may link PTSD to COVID-19. Conclusions: Our study suggests that PTSD was associated with increased risks for COVID-19 susceptibility and severity. Early diagnosis and effective treatment of PTSD in individuals infected with the coronavirus may improve the management of the outcomes of COVID-19.

Umbilical cord blood (UCB) is an advantageous source for hematopoietic stem/progenitor cell (HSPC) transplantation, yet the current strategies for large-scale and cost-effective UCB-HSPC preparation are still unavailable. To overcome these obstacles, we systematically evaluate the feasibility of our newly identified CH02 peptide for ex vivo expansion of CD34+ UCB-HSPCs. We herein report that the CH02 peptide is specifically enriched in HSPC proliferation via activating the FLT3 signaling. Notably, the CH02-based cocktails are adequate for boosting 12-fold ex vivo expansion of UCB-HSPCs. Meanwhile, CH02-preconditioned UCB-HSPCs manifest preferable efficacy upon wound healing in diabetic mice via bidirectional orchestration of proinflammatory and anti-inflammatory factors. Together, our data indicate the advantages of the CH02-based strategy for ex vivo expansion of CD34+ UCB-HSPCs, which will provide new strategies for further development of large-scale HSPC preparation for clinical purposes.

Psoriasis is a systemic immune-mediated inflammatory disease that presents at any age and is characterized by excessive proliferation and abnormal differentiation of keratinocytes as well as infiltration of multiple inflammatory cells. It has been gradually attracting more attention because of not only the increased risk of cardiovascular, metabolic, and autoimmune-related diseases but also the accompanying depression, anxiety, self-affirmation impairments, dementia, sleep disorders, and other mental disorders that place a substantial psychosocial burden on society and individuals. Mental and psychological disorders are involved in the occurrence, development, outcome, recurrence, and treatment of psoriasis through the neuroendocrine-immune signaling network. This review summarizes the pathogenesis of psychological and psychological disorders in patients with psoriasis with the aim of deepening clinicians’ awareness of the mental and psychiatric comorbidities in patients with psoriasis.

Abstract Resistance to epidermal growth factor tyrosine kinase inhibitors (EGFR-TKI) remains one of the major challenges in lung adenocarcinoma (LUAD) therapy. Here, we find an increased frequency of the L12_16 amino acid deletion mutation in the signal peptide region of NOTCH4 (NOTCH4ΔL12_16) in EGFR-TKI-sensitive patients. Functionally, exogenous induction of NOTCH4ΔL12_16 in EGFR-TKI -resistant LUAD cells sensitizes them to EGFR-TKIs. This process is mainly mediated by the reduction of the intracellular domain of NOTCH4 (NICD4) caused by the NOTCH4ΔL12_16 mutation, which results in a lower localization of NOTCH4 in the plasma membrane. Mechanistically, NICD4 transcriptionally upregulates the expression of HES1 by competitively binding to the gene promoter relative to p-STAT3. Because p-STAT3 can downregulate the expression of HES1 in EGFR-TKI-resistant LUAD cells, the reduction of NICD4 induced by NOTCH4ΔL12_16 mutation leads to a decrease in HES1. Moreover, inhibition of the NOTCH4-HES1 pathway using inhibitors and siRNAs abolishes the resistance of EGFR-TKI. Overall, we report that the NOTCH4ΔL12_16 mutation sensitizes LUAD patients to EGFR-TKIs through transcriptional down-regulation of HES1 and that targeted blockade of this signaling cohort could reverse EGFR-TKI -resistance in LUAD, providing a potential approach to overcome resistance to EGFR-TKI -therapy.

Friction stir processing (FSP) with high rotating speed were successfully employed to fabricate a novel AZ31 magnesium matrix composites (MMCs) reinforced by biological particles of nano-hydroxyapatite (nHA) and nano-magnesium oxide (nMgO). The influences of tool rotating speed on the microstructure evolution, mechanical properties and corrosion resistance of MMCs were investigated. In results, high rotating speed not only significantly refined the grains of the stirred zone (SZ) in MMCs due to sufficient dynamic recrystallization (DRX), but also reduced the size of β-Al12Mg17 precipitates and caused them homogeneously distributed. With the increase of rotating speed, the bio-reinforced particles exhibited a larger range with uniform distribution in SZ of MMCs, and the microhardness, tensile strength and corrosion resistance of MMCs were also improved. At high rotating speed of 6000 rpm, MMCs had a maximum tensile strength of 235.5 MPa with cleavage fracture of ductile-brittle mixed mode. Meanwhile, the self-corrosion potential of MMCs (−1.408 V) was 10.4% higher than the matrix (−1.571 V), while the self-corrosion current density (9.328 × 10−5 A/cm2) was 96.4% much lower than the matrix (2.607 × 10−3 A/cm2), indicating that the corrosion resistance of MMCs was significantly enhanced than matrix. And the corrosion morphologies of MMCs presented mud cracking due to relatively uniform corrosion.

Abstract Purpose Esophageal squamous cell carcinoma (ESCC) remains one of the most common causes of cancer death due to the lack of effective therapeutic options. New targets and the targeted drugs are required to be identified and developed. Methods Highly expressed genes in ESCA were identified using the edgeR package from public datasets. Immunostaining assay verified the high expression level of EFNA1 in ESCC. CCK-8, colony formation and wound healing assays were performed to examine the role of EFNA1 and EPHA2 in ESCC progression. Cell cycle was analyzed by flow cytometry and autophagy activation was determined by autophagolysosome formation using transmission electron microscopy. The small molecule targeting to EFNA1 was identified by molecular docking and the anti-tumor effects were verified by in vitro and in vivo models with radiation treatment. Results EFNA1 was highly expressed in esophageal cancer and significantly associated with poor prognosis. Downregulation of EFNA1 remarkably inhibited cell proliferation and migration. Furthermore, decreased EFNA1 significantly suppressed the expression of cMYC along with its representative downstream genes involved in cell cycle, and activated autophagy. Similar effects on ESCC progression were obtained from knockdown of the corresponding receptor, EPHA2. The potential small molecule targeting to EFNA1, salvianolic acid A (SAA), could significantly suppress ESCC progression and increase the sensitivity to radiotherapy. Conclusion We revealed that EFNA1 facilitated the ESCC progression via the possible mechanism of activating cMYC-modulated cell proliferation and suppressing autophagy, and identified SAA as a potential drug targeting EFNA1, providing new options for the future treatments for ESCC patients.

Abstract Owing to the lack of appropriate protection measures, natural and human factors have led to the deterioration of rockeries, which are a distinct cultural heritage with both aesthetic and historical value and an essential component of Chinese classical gardens. The state of rockeries is evaluated by craftsmen who assess the damage levels based on their experience. While this is a common practice, it lacks standardization, which may cause a great uncertainty that influences the efficiency of the protection of rockeries. The preservation and risk mitigation of cultural heritages require the use of reliable tools that provide an accurate diagnosis of their conditions. Multi-criteria decision-making techniques have been applied in several previous studies and proven to be a reliable method for conducting vulnerability or risk assessment for cultural heritage. Therefore, this study developed a health risk assessment tool based on multi-criteria decision-making techniques that can be applied to rockeries in Chinese classical gardens. In contrast to other multi-criteria decision-making methodologies, the proposed method emphasizes the detailed analysis of the health state of rockeries based on impartial and objective data. Moreover, based on the ultimate risk rating for rockeries, the decision makers can arrange the priorities of action in a hierarchical manner, and the cost-efficient protection measures can be identified. Results from the application of four different case studies are illustrated to demonstrate the usefulness of the proposed method.

Biochar-based materials, derived from renewable biomass resources, have emerged as promising candidates for electroanalytical applications due to their unique physicochemical properties, such as high surface area, excellent biocompatibility, and good chemical stability. This review provides a comprehensive overview of recent advancements in the development and application of biochar-based materials in electrochemical devices, including sensors, energy storage, and catalysis. We discuss the synthesis and functionalization of biochar materials, focusing on the effects of feedstock and pyrolysis conditions on their properties. The applications of biochar-based materials in electrochemical devices are reviewed, with a particular emphasis on enzyme-based biosensors, DNA-based biosensors, and immunosensors. Despite their promising performance, challenges such as reproducibility, electrical conductivity, and long-term stability need to be addressed to facilitate their widespread adoption in the industry. We also discuss emerging trends, such as the development of multifunctional hybrid materials and integration into flexible devices. Finally, we highlight the importance of policy, regulatory aspects, and environmental assessments to ensure the safe and sustainable use of biochar-based materials in electroanalytical applications.