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When simulating drying-rewetting process of grid cells in numerical groundwater modeling using the block-centered finite-difference approach, the models is highly probable to run into non-convergence, which could greatly affect the applicability of groundwater models. This study used ideal case and practical simulation in Denmark to comprehensively compare the simulation capabilities and characteristics of two algorithms, namely the empirical trial (ET) method proposed by MODFLOW and the always active cell (AAC) method proposed by COMUS, in the drying-rewetting simulation. The results show that: (1) For the ET method, the selection of parameter combination has a significant influence on the model convergence and the simulation results. It is compulsory to continuously optimize the parameter to avoid model failures such as non-convergence and large simulation errors when using the ET method, which greatly increases the difficulty of groundwater model application and time cost. (2) The simulation results from the AAC method are more reliable than those from the ET method. Theoretically, the effect of the AAC method is equivalent to the optimal parameter set in the ET method. Therefore, parameter optimization is no longer needed in the AAC method, which can effectively reduce the difficulty of using groundwater models and meanwhile reduce the uncertainty of simulation results. (3) The numerical accuracy of the intercell horizontal hydraulic conductance in the AAC method is consistent with that of the classical harmonic average method, demonstrating that the AAC method can also be used in the simulation without the drying-rewetting process. In summary, the AAC method is more suitable for simulating the drying-rewetting process of groundwater model cells and is expected to be more widely used in groundwater numerical simulation.

Abstract The centrality of job satisfaction in fostering the stability and progression of the teaching cadre and in underpinning the effective operation of educational institutions is paramount. Drawing from motivation theory and the Job Demands-Resources model, this research delves into the influence of psychological empowerment on the job satisfaction of 533 preschool educators in China, employing the Psychological Empowerment Questionnaire, the Occupational Identity Questionnaire, and the Job Satisfaction Scale. The inquiry probes the intermediary function of occupational identity in the nexus between psychological empowerment and job satisfaction within the cohort of preschool teachers. The findings underscore that psychological empowerment substantially foretells heightened job satisfaction in preschool educators, and concurrently, occupational identity serves as a partial mediator in the association between psychological empowerment and job satisfaction. Augmenting levels of psychological empowerment and occupational identity among preschool teachers is a strategic avenue for fortifying their holistic contentment in their professional roles, thereby contributing indispensably to the fortification of a robust teaching workforce in kindergarten establishments.

Abstract Purpose Delirium has a significant impact on millions of people globally and is closely linked to an unfavorable prognosis for complications. Observational studies suggest that plasma metabolites may play significant roles as markers and effectors of delirium, but causal relationships have not yet been elucidated. Based on the most recent genome-wide association study (GWAS) data, our study aims to present novel insights into the genetic relationship between delirium and plasma metabolites. This investigation offers potential clues for utilizing plasma metabolites as predictors of delirium development. Methods We performed a thorough Mendelian randomization (MR) analysis to investigate the causal relationship between 1,091 individual metabolites and 309 metabolite ratios in plasma with respect to delirium. Inverse-variance weighting (IVW) was employed as the primary estimation method, while MR-Egger and weighed median methods were utilized to assess the robustness of the results. Sensitivity analyses encompassing the MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test, Cochran Q test, leave-one-out analysis and MR Egger intercept analysis were also undertaken. Additionally, the MR Steiger test was performed to explore any potential reverse causal effect of metabolites on delirium. Results A total of 63 types of plasma metabolites associated with delirium were detected using the IVW method (p < 0.05). Among the known metabolites, our analysis revealed that two specific metabolites (1-palmitoyl-2-palmitoleoyl-gpc (16:0/16:1) and homovanillate) and a metabolite ratio (phosphate to oleoyl-linoleoyl-glycerol (18:1 to 18:2)) demonstrated a consistent and significant causal relationship with delirium across all analysis methods. Finally, no evidence of pleiotropy was detected in our analysis. Conclusions Our study has revealed a causal association between blood metabolites and the risk of delirium. homovanillate is known to be associated with immunity and redox, 1-palmitoyl-2-palmitoleoyl-gpc (16:0/16:1) and metabolite ratio (phosphate to oleoyl-linoleoyl-glycerol (18:1 to 18:2)) may play a role in lipid regulation. These findings may provide fresh insights into the identification of suitable diagnostic markers and potential treatment strategies focused on specific plasma metabolites in patients with delirium. However, further experiments are required to gain a comprehensive understanding of the underlying biological mechanisms involved.

Abstract Natural killer (NK) cell-based therapies have made great progress in treating both hematological and solid tumors. Their unique mechanism of action does not rely on antigen presentation to recognize and eliminate tumor cells, making them a promising approach for cancer immunotherapy. In this review, we present a comprehensive summary of the latest clinical data of the novel NK cell-based therapies from the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, highlighting the potential of these advancements to revolutionize the treatment of hematologic malignancies and solid tumors.

Abstract Background There is currently scarcity of information on small cell neuroendocrine carcinoma of the nasopharynx (SCNEC-nasopharynx). It is believed that this type of cancer is not associated with Epstein-Barr virus (EBV) infection and is indistinguishable from classic SCNEC occurring in other organs. Materials and methods Herein we provided 3 cases of nasopharyngeal mass in our hospital, two males and one female. On admission, these patients were considered nasopharyngeal carcinoma with lymph node metastasis, and one of them had liver metastasis. The nasopharyngeal mucosal tissues were biopsied for pathological examination including immunohistochemistry and in situ hybridization. PubMed database was searched for articles about SCNEC-nasopharynx published up to April 2024 in any language. Result The 3 cases had similar histological features of SCNEC in other organs but differed in rich- tumor-infiltrating lymphocytes (TILs). All of them stained for pancytokeratin (panCK) and epidermal growth factor receptor (EGFR). Case 1 and Case 2 diffusely expressed insulinoma-associated protein 1(INSM-1) and synaptophysin (Syn), Case 3 strongly stained for CD56 and Syn. Immunostaining of all 3 cases for p40, p63, TTF-1, CK20, S-100 and NUT showed negative. BRG-1, INI-1 and Rb were retained. And p53 all showed wild-type expression. The Ki-67 labeling indiced of case 1, 2, and 3 were 80%, 90%, and 80%, respectively. In situ hybridization showed strong and uniform nuclear positivity of EBV-encoded small RNAs (EBER) in the neoplastic cells of 3 cases. Conclusion EBV-positive SCNEC-nasopharynx was exactly rare. The origin of this tumor is still controversial. It may originate from EBV-infected mucosal epithelium like nasopharyngeal carcinoma. Based on our cases and relevant literature, we found EBV-positive SCNEC-nasopharynx as a probably site-specific subtype of SCNEC with differing pathogenetic mechanism. The subtype not only virus positivity but also that it was associated with TILs and did not show p53 or Rb alterations by immunohistochemistry. It may be more responsive to treatment and have a better prognosis than classic SCNEC. We will continue to follow-up these patients and collect additional cases to further understand the unique biology of this rare solid tumor.

Objective: To summarize the imaging and clinical features of ovarian Sertoli–Leydig cell tumors (SLCT) to improve our understanding of the disease. Methods: The clinical and imaging data of 15 patients with SLCT confirmed by surgery and pathology were analyzed retrospectively. All patients underwent contrast-enhanced MRI, and five patients underwent contrast-enhanced CT. The expression levels of tumor markers and endocrine hormones were detected in 15 and 10 patients, respectively. Results: All 15 cases of SLCT were unilateral: 8 tumors in the left accessory and 7 tumors in the right accessory, and 4 solid tumors and 11 cystic solid tumors. MRI findings showed that solid components in masses were mainly indicated by intermediate intensity on T1WI and slight hyperintensity on T2WI, while cystic components were indicated by hypo-signal on T1WI and hyper-signal on T2WI. Solid components showed hyper-signals on DWI and hypo-signals on the ADC map. Four cases of solid tumors showed marked enhancement; all the solid components in five cases of cystic solid tumors showed marked enhancement, presenting as nodular, irregular septa, or cystic wall; and the other six cases of cystic solids showed mixed enhancement after administration of contrast medium. Among the six cases of mixed enhancement, five were moderately to poorly differentiated, and one was moderately differentiated. CT findings revealed that the solid components had soft tissue density, whereas cystic components had watery density. Three cases of solid tumors showed marked enhancement, while two cases of cystic solid tumors showed marked enhancement of the solid components or mixed enhancement. Nine patients had increased testosterone levels . Three patients had elevated AFP levels, two had elevated CA125 levels, and one had raised CA199 levels. Ten patients presented with androgen stimulation-related symptoms, two with estrogen stimulation-related symptoms, two with the co-action of estrogen and androgen and one without symptoms. Histopathological results showed that two cases were highly differentiated, seven were moderately differentiated, five were moderately to poorly differentiated, and one was poorly differentiated. Conclusion: SLCT presents as a solid or cystic solid mass, and solid components show either marked or mixed enhancement. Patients with moderate-to-poor and poor differentiation may present with mixed enhancement. SLCT often presents with symptoms related to stimulation of hormones, most commonly androgen.

The grassland areas in eastern Inner Mongolia and northern Xinjiang are rich in coal and groundwater resources. The mining fissures formed by high-intensity coal mining are easy to lead to the strong water-rich aquifer, and it is very easy to cause the destruction of the groundwater system in the overlying strata, the accident of water inrush and sand inrush is easy to happen, especially the height of coal caving is difficult to control in fully mechanized top coal caving mining under aquifer. In this paper, the system protection of overlying aquifer in extra-thick coal seam is taken as the research object, the protection of aquifer and the safety control of water-sand disaster are the research objectives, and the key technology of intelligent caving for overlying aquifer protection in extra-thick coal seam is developed, based on the technology of preventing and controlling water inrush and sand inrush in coal mine, the fundamental way of protecting the groundwater system above the extra-thick coal seam is obtained. An intelligent top-coal caving technology is developed and applied, including top-coal movement tracking system, multi-round memory caving method and system. Based on the precise exploration of hydrogeological conditions, the actual measurement of overburden failure height and the determination of top coal caving height, the intelligent top coal caving technology of multi-round coal caving is applied to Control the height of mining fracture zone. Taking the applied working face as an example, the hydrogeological fine exploration and drilling verification, the acquisition of overburden failure height and the intelligent top-coal caving technology are applied, the safety and precise control of water-sand disaster in overlying aquifer is realized in the process of mining, and the overlying strong water-rich aquifer is effectively protected.

Abstract Background Migratory birds exhibit heterogeneity in foraging strategies during wintering to cope with environmental and migratory pressures, and gut bacteria respond to changes in host diet. However, less is known about the dynamics of diet and gut fungi during the wintering period in black-necked cranes (Grus nigricollis). Results In this work, we performed amplicon sequencing of the trnL-P6 loop and ITS1 regions to characterize the dietary composition and gut fungal composition of black-necked cranes during wintering. Results indicated that during the wintering period, the plant-based diet of black-necked cranes mainly consisted of families Poaceae, Solanaceae, and Polygonaceae. Among them, the abundance of Solanaceae, Polygonaceae, Fabaceae, and Caryophyllaceae was significantly higher in the late wintering period, which also led to a more even consumption of various food types by black-necked cranes during this period. The diversity of gut fungal communities and the abundance of core fungi were more conserved during the wintering period, primarily dominated by Ascomycota and Basidiomycota. LEfSe analysis (P 2) found that Pyxidiophora, Pseudopeziza, Sporormiella, Geotrichum, and Papiliotrema were significantly enriched in early winter, Ramularia and Dendryphion were significantly enriched in mid-winter, Barnettozyma was significantly abundant in late winter, and Pleuroascus was significantly abundant in late winter. Finally, mantel test revealed a significant correlation between winter diet and gut fungal. Conclusions This study revealed the dynamic changes in the food composition and gut fungal community of black-necked cranes during wintering in Dashanbao. In the late wintering period, their response to environmental and migratory pressures was to broaden their diet, increase the intake of non-preferred foods, and promote a more balanced consumption ratio of various foods. Balanced food composition played an important role in stabilizing the structure of the gut fungal community. While gut fungal effectively enhanced the host’s food utilization rate, they may also faced potential risks of introducing pathogenic fungi. Additionally, we recongnized the limitations of fecal testing in studying the composition of animal gut fungal, as it cannot effectively distinguished between fungal taxa from food or soil inadvertently ingested and intestines. Future research on functions such as cultivation and metagenomics may further elucidate the role of fungi in the gut ecosystem.

Abstract Background There is growing evidence indicating that deubiquitinating enzymes may contribute to tumor progression and can serve as promising therapeutic targets. Methods The overexpression of deubiquitinase OTUD6B in lung adenocarcinoma (LUAD) and its adjacent tissues was analyzed by immunohistochemistry and TCGA/GO database. Survival analysis further supported OTUD6B as a potential target for LUAD treatment. We assessed the effect of OTUD6B on LUAD cell growth using cell viability assays and conducted TUNEL staining, migration, and invasion experiments to investigate the impact of OTUD6B on the apoptosis and metastasis of LUAD cells. Additionally, we established a transplanted tumor model in nude mice to validate our findings in vivo. Finally, using IP mass spectrometry and co-IP experiments, we screened and confirmed the influence of RIPK1 as a substrate of OTUD6B in LUAD. Results OTUD6B is highly overexpressed in human LUAD and predicts poor prognosis in LUAD patients. OTUD6B knockdown inhibited the proliferation of LUAD cells and enhanced apoptosis and inhibited metastasis in LUAD cells suppressed. A549 xenografts revealed that OTUD6B deletion can slow down tumour growth. Additionally, OTUD6B can bind to RIPK1, reduce its ubiquitination level and increase its protein stability. Conclusions Our results suggest that OTUD6B is a promising clinical target for LUAD treatment and that targeting OTUD6B may constitute an effective anti-LUAD strategy.

Abstract Traditional DID models overlook variations in policy intensity, causing estimation deviations from the actual situation and a limited understanding of the influence mechanism. In response, the Intensity Modified SDID Model is built to examine the influence mechanism of ETS's carbon reductions. Moreover, through model extensions, the study explores the spatiotemporal characteristics and heterogeneities of ETS’s effects. Results show that: (1) "Dual-circulation" influence mechanism is confirmed, where ETS directly contributes to carbon reductions (2.70% to 10.0% impact) through external pathways, and internal pathways continuously strengthen reduction effects, comprehensive mechanisms are thereby formed and enhanced based on interaction among internal and external pathways. (2) Reasonable ETS levels are estimated and proposed to achieve "Dual Carbon Target", constraining nationwide carbon quotas by 20 billion tons/year, increasing carbon trading volumes by 80 thousand tons/year, and elevating the carbon trading prices by 100 RMB (14 USD) per ton. (3) ETS's carbon reduction effects are identified with temporal and spatial characteristics, temporally, effects peak in the 4th period (Event +4 ) but diminish in the 5th period (Event +5 ), spatially, effects peak in areas distancing around 1000 km but disappear beyond 1500 km. (4) ETS also has synergistic effects with atmospheric pollution reduction, including industrial emissions of sulfur dioxide and smoke (dust), but are insignificant to industrial emissions of wastewater and solid waste.

Abstract To solve the problem of oscillation instability in permanent magnetic synchronous generator (PMSG)-based wind power connected systems during low-voltage ride through (LVRT) process, a parameter adjustment strategy based on interaction energy path optimization is proposed in this paper. Firstly, a modular state-space model of PMSG under fault transient conditions is constructed, and the system is divided into five subsystems. Then, the dynamic energy function of subsystems reflecting the oscillation stability of the system is derived. Based on that, the dynamic energy flow path is described considering the introduction of LVRT control. On this basis, the interaction energy between LVRT control links and subsystems is analyzed, and the coupling mechanism of voltage support and damping characteristics in the LVRT process is explained. Further, aiming at the optimal change rate of the total interaction energy in the LVRT process, the adjustment strategy of LVRT control parameters is constructed to meet voltage and damping requirements. Finally, a PMSG-connected system model is built on the MATLAB/Simulink platform to verify the effectiveness of the adjustment strategy. The results show that the proposed method can effectively improve the damping level under the fault transient condition, as well as supporting system voltage.

Abstract Objective To translate Amyotrophic Lateral Sclerosis-Specific Quality of Life-Short Form (ALSSQOL-SF) and test its reliability and validity, so that explore feasibility in Chinese mainland and make up the gap of specific tools for measuring quality of life of patients with ALS. Methods This was a cross-sectional design. The Brislin translation model was used to translate ALSSQOL-SF, and the Chinese version of ALSSQOL-SF (C-ALSSQOL-SF) was revised through cultural adaptation and pre-test. The convenience sampling method was used to investigate 138 patients with ALS in Tianjin to test the reliability and validity of the C-ALSSQOL-SF. Results The C-ALSSQOL-SF included 20 items, covering 6 dimensions: physical symptoms, bulbar function, negative emotion, interaction with people and the environment, religiosity and intimacy. The scale-level content validity index (S-CVI) of C-ALSSQOL-SF was 0.964, and the item-level content validity index (I-CVI) was between 0.857 to 1.000. The results of Confirmatory Factor Analysis (CFA) showed that CMIN/DF = 1.161, RMSEA = 0.034, GFI = 0.892, IFI = 0.976, TLI = 0.969, CFI = 0.975, and the 6-factor model fitted well. The scores of C-ALSSQOL-SF and WHOQOL-BREF were positively correlated (r = 0.745). The Cronbach’s α coefficient of the scale was 0.85, the Cronbach’s α coefficient of each dimension was between 0.59 to 0.86, and the split-half reliability was 0.78. Conclusion The Chinese version of ALSSQOL-SF has good reliability and validity, and can be used as a tool to evaluate the quality of life of patients with ALS in Chinese mainland.

Abstract Background Radiotherapy interruption (RTI) prolongs the overall total treatment time and leads to local control loss in many cancers, but it is unclear in esophageal cancer. We aimed to evaluate the influence of RTI on the overall survival (OS), progression-free survival (PFS), and local-regional recurrence-free survival (LRFS) of patients with esophageal cancer undergoing chemoradiotherapy. Methods A total of 299 patients with esophageal squamous cell carcinoma from 2017 to 2019 were retrospectively analyzed to investigate the effect of RTI on OS, PFS, and LRFS. The delayed time of radiotherapy interruption was calculated as the actual radiation treatment time minus the scheduled time. The univariate and multivariate analyses were performed by the COX proportional hazards regression models, and the survival analysis was performed through the Kaplan‒Meier method, and compared with the log-rank test. Results The 3-year OS, PFS, and LRFS rates were 53.0%, 42.0%, and 48.0%, respectively. The univariate and multivariate analyses showed that the delayed time > 3 days was an independent adverse prognostic factor for OS (HR = 1.68, 95% CI 1.10–2.55, p = 0.016), and LRFS (HR = 1.74, 95% CI 1.18–2.57, p = 0.006). The patient with a delayed time of > 3 days had poorer survival rates of OS, and LRFS than patients with a delayed time of ≤ 3 days (OS, p = 0.047; LRFS, p = 0.013), and the survival outcomes of patients with shorter delayed time (1–3 days) were slightly different from the patients without interruptions. The impact of delay time on PFS is not statistically significant, but the survival outcomes of the two groups were slightly different. Conclusion There was a significant correlation between delayed time and local control of esophageal cancer. The delayed time for more than 3 days might decrease the survival outcome, and increase the local recurrence risk.

Abstract Background Freezing stress is one of the major abiotic stresses that causes extensive damage to plants. LEA (Late embryogenesis abundant) proteins play a crucial role in plant growth, development, and abiotic stress. However, there is limited research on the function of LEA genes in low-temperature stress in Brassica napus (rapeseed). Results Total 306 potential LEA genes were identified in B. rapa (79), B. oleracea (79) and B. napus (148) and divided into eight subgroups. LEA genes of the same subgroup had similar gene structures and predicted subcellular locations. Cis-regulatory elements analysis showed that the promoters of BnaLEA genes rich in cis-regulatory elements related to various abiotic stresses. Additionally, RNA-seq and real-time PCR results indicated that the majority of BnaLEA family members were highly expressed in senescent tissues of rapeseed, especially during late stages of seed maturation, and most BnaLEA genes can be induced by salt and osmotic stress. Interestingly, the BnaA.LEA6.a and BnaC.LEA6.a genes were highly expressed across different vegetative and reproductive organs during different development stages, and showed strong responses to salt, osmotic, and cold stress, particularly freezing stress. Further analysis showed that overexpression of BnaA.LEA6.a increased the freezing tolerance in rapeseed, as evidenced by lower relative electrical leakage and higher survival rates compared to the wild-type (WT) under freezing treatment. Conclusion This study is of great significance for understanding the functions of BnaLEA genes in freezing tolerance in rapeseed and offers an ideal candidate gene (BnaA.LEA6.a) for molecular breeding of freezing-tolerant rapeseed cultivars.

Abstract To evaluate the influence distance and evolution law of the jet blast under the full thrust state of the aircraft engine, we constructed a refined single-engine nozzle model in this study. Using a specific B737-800 engine as an illustrative example, this model takes into account both the internal combustion of the engine and the shearing effect of the tail cone on the airflow; based on a structured grid, the grid and far-field independence of the numerical solution were verified. The numerical simulation results obtained via the Fluent software were compared with the data outlined in the Boeing aircraft characteristics manual for a thorough analysis. Our results indicated that the calculated jet influence distance from the refined nozzle model aligns more closely with the data in the aircraft characteristics manual, albeit with superior accuracy compared to the simplified nozzle model employed in previous studies. The findings of this study can serve as a valuable reference for computing jet influence distances across various aircraft types and engine models, providing data support for the study of safety intervals for aircraft crossing the runway behind the takeoff point.

The investigation of hidden structures and the prediction of gas abnormal area form the foundation of gas disaster prevention engineering. In accordance with the laws and regulations governing coal mining in our country, a gas pumping project must be implemented prior to mining coal seams with a gas hazard. Typically, geologic anomaly area represent gas hazard zones, where the combination of tectonic stress field and mining-induced stress field can disturb coal bodies and pressurize gas. To accurately locate geologic anomaly areas and evaluate their gas disaster potential, a gas geologic anomaly survey method has been proposed based on gas extraction projects. This method uses drilling parameters and records to calculate the coordinates of the control points of the coal seam roof and bottom, and then utilizes two-dimensional projection diagrams and three-dimensional stress field models to survey and forecast small, hidden geological structures (such as small faults, folds, and locally abnormal coal thicknesses). By analyzing the additional stress field surrounding small geological structures, gas disaster potential can be dynamically predicted. The application of this method enables the detailed investigation of geological anomalies and reveals the general pattern of gas geological evolution at coal mining worksites. The research results provide a scientific basis for the optimal design and effective implementation of disaster prevention and control measures for coal seams with high gas content or at risk of gas outbursts.

Abstract Background Transposable elements (TEs) have a profound influence on the trajectory of plant evolution, driving genome expansion and catalyzing phenotypic diversification. The pangenome, a comprehensive genetic pool encompassing all variations within a species, serves as an invaluable tool, unaffected by the confounding factors of intraspecific diversity. This allows for a more nuanced exploration of plant TE evolution. Results Here, we constructed a pangenome for diploid A-genome cotton using 344 accessions from representative geographical regions, including 223 from China as the main component. We found 511 Mb of non-reference sequences (NRSs) and revealed the presence of 5479 previously undiscovered protein-coding genes. Our comprehensive approach enabled us to decipher the genetic underpinnings of the distinct geographic distributions of cotton. Notably, we identified 3301 presence-absence variations (PAVs) that are closely tied to gene expression patterns within the pangenome, among which 2342 novel expression quantitative trait loci (eQTLs) were found residing in NRSs. Our investigation also unveiled contrasting patterns of transposon proliferation between diploid and tetraploid cotton, with long terminal repeat (LTR) retrotransposons exhibiting a synchronized surge in polyploids. Furthermore, the invasion of LTR retrotransposons from the A subgenome to the D subgenome triggered a substantial expansion of the latter following polyploidization. In addition, we found that TE insertions were responsible for the loss of 36.2% of species-specific genes, as well as the generation of entirely new species-specific genes. Conclusions Our pangenome analyses provide new insights into cotton genomics and subgenome dynamics after polyploidization and demonstrate the power of pangenome approaches for elucidating transposon impacts and genome evolution.

Abstract Background Chimeric antigen receptor T (CAR-T) cell therapy, as an emerging anti-tumor treatment, has garnered extensive attention in the study of targeted therapy of multiple tumor-associated antigens in hepatocellular carcinoma (HCC). However, the suppressive microenvironment and individual heterogeneity results in downregulation of these antigens in certain patients’ cancer cells. Therefore, optimizing CAR-T cell therapy for HCC is imperative. Methods In this study, we administered FGFR4-ferritin (FGFR4-HPF) nanoparticles to the alpaca and constructed a phage library of nanobodies (Nbs) derived from alpaca, following which we screened for Nbs targeting FGFR4. Then, we conducted the functional validation of Nbs. Furthermore, we developed Nb-derived CAR-T cells and evaluated their anti-tumor ability against HCC through in vitro and in vivo validation. Results Our findings demonstrated that we successfully obtained high specificity and high affinity Nbs targeting FGFR4 after screening. And the specificity of Nbs targeting FGFR4 was markedly superior to their binding to other members of the FGFR family proteins. Furthermore, the Nb-derived CAR-T cells, targeting FGFR4, exhibited significantly enhanced anti-tumor efficacy in both experiments when in vitro and in vivo. Conclusions In summary, the results of this study suggest that the CAR-T cells derived from high specificity and high affinity Nbs, targeting FGFR4, exhibited significantly enhanced anti-tumor efficacy in vitro and in vivo. This is an exploration of FGFR4 in the field of Nb-derived CAR-T cell therapy for HCC, holding promise for enhancing safety and effectiveness in the clinical treatment of HCC in the future.

Abstract Homer1a and A2 astrocytes are involved in the regulation of inflammation induced by intracerebral hemorrhage (ICH). However, there is no anticipated treatment strategy based on the anti-inflammatory effect of Homer1a and A2 astrocytes. Here, we successfully induced A2 astrocytes in vitro, and then we report an efficient method to prepare Homer1a+ EVs derived from A2 astrocytes which making it more stable, safe, and targetable to injured neurons. Homer1a+ EVs promotes the conversion of A1 to A2 astrocytes in ICH mice. Homer1a+ EVs inhibits activation and nuclear translocation of NF-κB, thereby regulating transcription of IL-17A in neurons. Homer1a+ EVs inhibits the RAGE/NF-κB/IL-17 signaling pathway and the binding ability of IL-17A: IL17-AR and RAGE: DIAPH1. In addition, Homer1a+ EVs ameliorates the pathology, behavior, and survival rate in GFAPCreHomer1fl/−Homer1a± and NestinCreRAGEfl/fl ICH mice. Our study provides a novel insight and potential for the clinical translation of Homer1a+ EVs in the treatment of ICH.

Abstract Solid polymer electrolytes (SPEs) are pivotal in advancing the practical implementation of all‐solid‐state batteries. Poly(1,3‐dioxane) (PDOL)‐based electrolytes have attracted significant attention due to the pseudo‐high conductivity achieved through sophisticated in situ polymerization methods; however, such PDOL‐based electrolytes present challenges of crystallization over time and monomers residual during processing. In this study, integrating LiTFSI and LiDFOB as a universal copolymerization strategy for developing high‐performance PDOL electrolytes with a wide range of epoxy crosslinkers is proposed. It is discovered that this approach leverages the protective effects of TFSI anions on the boron active center and catalyzes polymer chain growth via crosslinking. The homogenously crosslinked (benzene‐centered) PDOL electrolyte exhibits remarkable thermo‐mechanical stability (up to 100 °C), high ion migration number (tLi+ = 0.42), a wide electrochemical window (≈5.0 V vs Li+/Li), and high ionic conductivity (4.5×10−4 S cm−1). Notably, the crosslinked PDOL electrolyte is in the all‐solid‐state with minimal monomer/oligomer residual, exhibiting no crystallization during relaxation, delivering a robust performance in all‐solid‐state lithium metal batteries.

Vibrio rotiferianus is a pathogenic bacterium that is widely distributed in the ocean and can cause diseases in a variety of marine animals, including fish, shrimp and shellfish. In this study, we isolated and identified V. rotiferianus strain TO-01 from diseased Trachinotus ovatus. Infected fish exhibited a range of pathological symptoms, including lethargy in swimming, blackened body coloration, skin ulceration and erratic side swimming. Tissue section examination revealed pronounced damage to the liver, spleen and gills of the infected fish. An analysis of immune factor expression revealed a significant increase in the expression of inflammatory factors, including interleukin (IL)-1, IL-2, IL-6 receptor and IL-21, in the spleen and kidney of fish infected with TO-01 at 6 h post-infection. To gain a more in-depth comprehension of the pathogenicity and drug resistance of V. rotiferianus, we conducted whole genome sequencing. The total genome length of V. rotiferianus was 4734,075 bp, and 74 virulence factors were predicted within the genome. Most of these virulence genes were associated with bacterial adhesion and flagellar motility. A gene associated with group sensing, cqsA, and a gene associated with hemolysin, tlh, were also identified. The prediction of drug resistance genes was in agreement with the results of drug sensitivity assays, both of which indicated that TO-01 has significant resistance to β-lactams. The findings of this study significantly enhance our understanding of the pathogenic mechanism of V. rotiferianus and give crucial insights into disease prevention and control in the management of T. ovatus.

The role of load modeling in power systems is crucial for both operational and regulatory considerations. It is essential to develop an effective and reliable method for optimizing load modeling parameter identification. In this paper, the dung beetle algorithm is improved by using the good point set, and a load model parameter identification strategy based on the good point set dung beetle optimization algorithm (GDBO) within the framework of the measurement-based load modeling method. The proposed parameter identification strategy involves utilizing PMU voltage data as input, selecting a comprehensive load model, and refining the initialization process based on the good point set to mitigate the influence of local maxima. Through iterative optimization of the objective function using the Dung Beetle Optimizer (DBO) algorithm, the optimal parameters for the comprehensive load model are determined, enhancing the model’s ability to accurately capture the power curve. Analysis of examples pertaining to PMU-measured modeling parameter identification reveals that the proposed GDBO algorithm, which incorporates a good point set, outperforms alternative methods such as the improved differential evolution algorithm (IDE), particle swarm optimization algorithm (PSO), grey wolf optimization algorithm (GWO), and conventional DBO algorithm. This demonstrates the superior performance of the introduced approach in the context of load model parameter identification.

BackgroundGeneralized pustular psoriasis (GPP) is a severe type of psoriasis. The current treatment primarily relies on corticosteroids and immunosuppressants. In recent years, biologics have been increasingly utilized in the treatment of this disease, and have demonstrated good clinical efficacy. However, children and adolescents are primarily treated with immunosuppressants, which have limited clinical application due to the serious side effects they may cause. At the same time, the effectiveness of current treatments is unsatisfactory. Secukinumab has been widely reported to be effective and safe in treating this disease. However, there are still insufficient data on its use in treating GPP in children.ObjectiveTo conduct a systematic review of the existing literature on the use of secukinumab for treating generalized pustular psoriasis in children and adolescents, and to evaluate its clinical effectiveness and safety.MethodsWe conducted a systematic review of all the literature reporting on the treatment of GPP in children and adolescents with secukinumab.ResultsA total of 7 papers (46 patients) were included in this study. After 12 weeks of treatment, all 46 participants were able to achieve a GPPASI score of 90 or higher, with approximately 96% of patients achieving complete clearing of the lesions (GPPASI 100 or JDA0). Adverse events were reported in 8 patients, the rate of adverse reactions was approximately 17%.ConclusionThe treatment of GPP in children and adolescents with secukinumab has a rapid onset of action and a high safety profile. However, the results of the literature may be influenced by publication bias.

Background: Breast cancer (BC) is a highly common form of cancer that occurs in many parts of the world. However, early -stage BC is curable. Many patients with BC have poor prognostic outcomes owing to ineffective diagnostic and therapeutic tools. The ubiquitination system and associated proteins were found influencing the outcome of individuals with cancer. Therefore, developing a biomarker associated with ubiquitination genes to forecast BC patient outcomes is a feasible strategy. Objective: The primary goal of this work was to develop a novel risk score signature capable of accurately estimate the future outcome of patients with BC by targeting ubiquitinated genes. Methods: Univariate Cox regression analysis was conducted utilizing the E1, E2, and E3 ubiquitination-related genes in the GSE20685 dataset. Genes with p

In this study, a compressible supersonic numerical model was established based on the open-source computational fluid dynamics software OpenFOAM. The supersonic air inflow was set in sinusoidal variation and gas hydrogen was employed as fuel for the DLR engine numerical simulation. The SST k-ω model and a 9-species 27-reaction hydrogen/oxygen chemical reaction model was employed as the turbulence and reaction mechanical kinetics models respectively. The effect of continuous variable inflow on the combustion performance for the scramjet engine was analyzed and the results showed that the combustion flame inside the scramjet engine exhibited significant partitioning phenomena around the combustion stabilization zones under periodic continuous variable inflow conditions. It was found that intense combustion zones were formed at both upstream and downstream flow as the induction of intersecting shock waves. When the flame was stabilized in the engine, the initiation position of the intense combustion zone at the upstream was transferred to the distance of twice the strut length, while the initiation position of the intense combustion zone at the downstream was anchored at a distance of about five times the strut length.

Abstract Short‐term load forecasting is critical for power system planning and operations, and ensemble forecasting methods for electricity loads have been shown to be effective in obtaining accurate forecasts. However, the weights in ensemble prediction models are usually preset based on the overall performance after training, which prevents the model from adapting in the face of different scenarios, limiting the improvement of prediction performance. In order to improve the accurateness and validity of the ensemble prediction method further, this paper proposes an ensemble deep reinforcement learning approach using Q‐learning dynamic weight assignment to consider local behaviours caused by changes in the external environment. Firstly, the variational mode decomposition is used to reduce the non‐stationarity of the original data by decomposing the load sequence. Then, the recurrent neural network (RNN), long short‐term memory (LSTM), and gated recurrent unit (GRU) are selected as the basic power load predictors. Finally, the optimal weights are ensembled for the three sub‐predictors by the optimal weights generated using the Q‐learning algorithm, and the final results are obtained by combining their respective predictions. The results show that the forecasting capability of the proposed method outperforms all sub‐models and several baseline ensemble forecasting methods.

ObjectiveSeveral studies have investigated the correlation between blood lipids and homocysteine, but no clear conclusions have been defined yet. Therefore, we utilized data from National Health and Nutrition Examination Survey (NHANES) to explore the correlation between serum homocysteine (Hcy) levels and hyperlipidemia, which is determined by the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). We believe this study can provide a scientific basis for the prevention and treatment of lipid abnormalities.MethodsThe data used in this study were sourced from NHANES 1999–2006, linked with National Death Index mortality data from January 1999 to December 2019. We employed logistic regression to assess the associations between Hcy levels and the presence of hyperlipidemia. Additionally, survival analysis using Kaplan-Meier estimate and Cox proportional hazards regression model was conducted to evaluate the associations between Hcy levels and all-cause mortality in the hyperlipidemia population.Results(1) A total of 13,661 subjects were included in the study. There were statistically significant differences in Hcy levels across different groups based on gender, age, race, marital status, education level, hypertension status, diabetes status, and Body Mass Index (BMI) (P

Joint stiffness and fibrosis are common complications that affect mobility and quality of life, necessitating effective therapeutic strategies to alleviate these issues. The study aimed to observe the therapeutic effect of static progressive stretching (SPS) combined with botulinum toxin type A (BTX-A) on knee joint stiffness in rats and its effect on the transforming growth factor beta 1 (TGF-β1)/small mother against decapentaplegic (Smad) pathway in the development of joint capsule fibrosis. Forty Sprague Dawley rats were randomly divided into the blank control group, model control group, SPS intervention group, BTX-A intervention group, and SPS combined with BTX-A intervention group. Except for the blank control group, the right knee joints of the other rats were surgically fixed with Kirschner wire internal immobilization in full flexion for four weeks to form joint flexion contracture and cause fibrotic stiffness of the joint. The therapeutic effect of each intervention was assessed by the range of motion (ROM) of the knee joint, joint stiffness, the number of total cells, and collagen deposition in the posterior joint capsule, as well as the protein level expressions of TGF-β1, Smad2, Smad3, Smad4, p-Smad2/3, collagen I and III, and alpha smooth muscle actin (α-SMA) in the posterior joint capsule in the TGF-β1/Smad pathway. SPS combined with BTX-A was more effective in relieving joint fibrosis stiffness, improving the histopathological changes in the posterior joint capsule, and suppressing the high expression of target proteins and the overactivated TGF-β1/Smad pathway. The overactivated TGF-β1/Smad pathway was involved in the formation of knee joint fibrosis stiffness in rats. SPS combined with BTX-A was effective in relieving joint flexion contracture and fibrosis of the joint capsule. Moreover, the inhibition of the overactivated TGF-β1/Smad pathway may be the potential molecular mechanism for its therapeutic effect.

To overcome the poor solubility, permeability, and bioavailability of the plant isoflavone daidzein (DAI), a novel salt of DAI with anhydrous piperazine (PIP) was obtained based on cocrystallization strategy. The new salt DAI-PIP was characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier-transform infrared (FT-IR) spectroscopy, and optical microscopy. The results showed that the maximum apparent solubility (Smax) of DAI-PIP increased by 7.27-fold and 1000-fold compared to DAI in pH 6.8 buffer and water, respectively. The peak apparent permeability coefficient (Papp) of DAI-PIP in the Caco-2 cell model was 30.57 ± 1.08 × 10−6 cm/s, which was 34.08% higher than that of DAI. Additionally, compared to DAI, the maximum plasma concentration (Cmax) value of DAI-PIP in beagle dogs was approximately 4.3 times higher, and the area under the concentration-time curve (AUC0-24) was approximately 2.4 times higher. This study provides a new strategy to enhance the dissolution performance and bioavailability of flavonoid drugs, laying a foundation for expanding their clinical applications.

Introduction The efficacy of belimumab in SLE has been demonstrated in randomised clinical trials, and its real-world effectiveness has been shown in studies in several countries. While belimumab was approved for treating SLE in China in 2019, data on its benefit in clinical practice are limited. This study will evaluate belimumab’s effectiveness in China, using practical clinical measures, such as Lupus Low Disease Activity State (LLDAS), to add to the body of real-world evidence.Methods and analysis The Real-world Effectiveness of beLImumAB in patients with systemic Lupus Erythematosus in China (RELIABLE) is an ambidirectional, observational descriptive cohort study across approximately 15 centres in China. Adults with SLE newly initiating belimumab with ≥1 measure of all five LLDAS components (SLE Disease Activity Index-2000; no new lupus disease activity; Physician Global Assessment; prednisolone-equivalent dose; immunosuppressants/biologics use) in the 3 months preceding belimumab initiation (index date) will be eligible and retrospectively and/or prospectively enrolled, depending on data availability. The retrospective follow-up will be ≤6 months, and retrospective and prospective patients will have a maximum 24-month follow-up. The primary objectives will be to describe the proportion of patients achieving LLDAS at 12 and 24 months post-index. The key secondary objective will be to describe the proportion of patients achieving LLDAS and each component at 3, 6, 9 and 18 months post-index. All data will be analysed descriptively; a statistical estimand will be applied to account for intercurrent events expected in a real-world setting.Ethics and dissemination This study will comply with all applicable laws regarding patient privacy; institutional review board approval will be obtained before the study commencement.Conclusions This study will evaluate belimumab’s effectiveness in patients with SLE initiating belimumab in clinical practice in China. Using LLDAS will provide clinicians with valuable insights into the impact of belimumab on the treat-to-target strategy with a relevant measure that can be repeated across the clinical practice.

ABSTRACT: Baicalein (BAI) is a natural flavonoid with antioxidant, antitumor and antibacterial properties. However, the bioavailability of BAI was limited due to low solubility. This study aims to improve the solubility of BAI through the amorphous solid dispersion (ASD) and evaluate changes in its pharmacokinetics and pharmacodynamics in Taihang chickens. Polyethylene caprolactam-polyvinyl acetate-polyethylene glycol grafted copolymer (Soluplus) was chosen as the carrier, and ASD was prepared by rotary evaporation and was characterized by powder X-ray diffractions (PXRD), differential scanning calorimetry (DSC) and fourier transform infrared spectroscopy (FT-IR). In vitro dissolution assays were used to screen the optimal ratio of drug to carrier, in vivo pharmacokinetic assays were conducted to investigate the promoting effect on the absorption. In addition, the effects of ASD on the growth performance, meat quality, antioxidant capacity and intestinal flora were investigated. ASD (1:9 and 2:8) did not exhibit crystal diffraction peaks of BAI in PXRD or endothermic peaks in DSC, indicating the successful preparation of ASD. The results of in vitro dissolution assay showed that the cumulative dissolution rate of ASD (2:8) within 600 min was 52.67%, which was 7.84-fold higher than BAI. The pharmacokinetic results showed that the peak concentration (Cmax) and the area under the drug-time curve (AUC0∼24) of ASD (2:8) was (5.20 ± 0.82) μg/mL and (17.03 ± 0.67) μg·h/mL, which was 1.91 and 2.64-fold higher than BAI, respectively. Dietary supplementation of BAI and ASD could increase average daily gain (ADG), while decrease feed conversion ratio (FCR), but there was no significant difference (P > 0.05). The drip loss of BAIASD group was lower than BAI group (P < 0.05). In addition, the antioxidant capacity of Taihang chickens were enhanced, the diversity and the abundance of beneficial bacteria was improved. Results of BAI upon the dietary supplementation tested in Taihang chickens, after preparation of ASD, indicating a superior enhancement effect in growth performance, meat quality, antioxidant capacity and intestinal flora due to an improved solubility and optimized bioavailability.

ABSTRACT: In laying hens, fatty liver hemorrhagic syndrome (FLHS) is a common metabolic disorder, which can affect egg production and nutritional value. However, the impact of FLHS on the lipid content in egg yolks was not clear. In this study, FLHS model was induced by using high-energy low-protein diet, and the egg quality was evaluated. Egg yolk lipids were quantitatively analyzed by using ultra-performance liquid chromatography-mass spectrometry combined with multivariate statistical analysis. Gene expressions of the lipoprotein were determined by qRT-PCR and antioxidant capacity of the egg yolk were determined by kits. The elevated blood lipids and extensive lipid droplets observed indicated successful establishment of the FLHS model in laying hens. Measurements of egg quality showed that egg yolk weight was increased in the FLHS group. Lipidomics revealed that 1,401 lipids, comprising 27 lipid subclasses in the egg yolk. According to score plots of principal component analysis and orthogonal partial least squares discriminant analysis, different lipid profile was observed between the control and FLHS groups. A total of 97 different lipid species were screen out. Sphingolipid and glycerophospholipid metabolism were identified as key pathways. Free polyunsaturated fatty acids (PUFA) exhibited an increase in the FLHS group (P < 0.05). Notably, the form of PUFAs was changed that the FLHS group showed an increase in triacylglycerol-docosahexenoic acid and triacylglycerol-arachidonic acid in the egg yolk, while triacylglycerol-α-linolenic acid was decreased (P < 0.05). Total superoxide dismutase was decreased in the egg yolks affected by FLHS. Gene expressions of vitellogenin 2 (VTG2), VTG3, very low-density apolipoprotein II and apolipoprotein B were increased in the liver of laying hens with FLHS (P < 0.05). In conclusion, FLHS promoted the lipid transport from the liver to the yolk by upregulating lipoprotein expression, which altered lipid profile, and reduced antioxidant capacity in the yolk. This study provided a foundation for understanding the changes in lipids, lipid transport and lipid antioxidation capacity in egg yolk from laying hens with FLHS.

BackgroundMultiple studies have shown a close relationship between changes in gut microbiota composition and obesity, and research results are influenced by factors such as race and geographical location, but there are few studies on children. ObjectiveTo analyze the diversity of gut microbiota related to obesity in a population of 2-6 years old, observe the distribution characteristics and species differences of gut microbiota between obese/overweight and normal weight groups, and explore the association betweenobese/overweight and gut microbiota diversity. MethodsFecal samples were collected from 74 children aged 2-6 years in Shanghai, including 18 obese/overweight individuals, 6 males and 12 females (male to female ratio of 1∶2), and 56 normal weight individuals, 18 males and 38 females (male to female ratio is nearly 1∶2). The 16S rDNA was extracted from bacteria in fecal samples, followed by PCR amplification, cDNA construction, and high-throughput sequencing. Naive Bayes algorithm was used to perform taxonomic analysis (phylum, class, order, family, genus, species) and community diversity analysis (Sobs index, Shannon index, Shannoneven index, Coverage index, PD index, and principal co-ordinates analysis) on representative sequences and abundance of amplicon sequence variants (ASV). Wilcoxon rank sum test, P-value multiple test correction, and analysis of similarities were used to test differences between the two groups to obtain information on the distribution characteristics and species differences of intestinal microbiota in children. ResultsSeventy-four fecal samples were sequenced, and the sequencing results were subjected to quality control and filtering. A total of 4905306 optimized sequences were obtained, resulting in 1860 ASVs. The diversity data analysis of ASVs generated 889 species annotation results at 8 taxonomic levels. The alpha diversity analysis showed that the richness (Sobs index), diversity (Shannon index), evenness (Shannoneven index), and phylogenetic diversity (PD index) of fecal community of the obese/overweight children were increased compared to those of the normal weight children, but there were no statistical differences between the two groups (P>0.05). The beta diversity analysis showed that there was little difference in the composition of microbial species between the two groups, and no significant clustering separation was observed. The results of species composition analysis at phylum, order, family, and genus levels of 74 samples showed a consistent core microbiota structure in the two groups of gut microbiota, but there were differences in microbiota composition. The differences in microbial community composition between the two groups were manifested at the taxonomic levels of order, family, and genus, among which phylum Firmicutes, order Erysipelotrichales, family Erysipelatocyclostridiaceae, genus Erysipelotrichaceae_ UCG-003 and genus Catenibacterium were significantly enriched in the obese/overweight group and contributed significantly to the phenotypic difference of obese/overweight [linear discriminant analysis (LDA)=3.72, P

Abstract Mobile edge computing (MEC) is a novel computing paradigm that pushes computation and storage resources to the edge of the network. The interconnection of edge servers forms small-scale data centers, enabling MEC to provide low-latency network services for mobile users. Nowadays, Remote Direct Memory Access (RDMA) has been widely deployed in such data centers to reduce CPU overhead and network latency. Plenty of congestion control mechanisms have been proposed for RDMA data centers, aiming to provide low-latency data delivery and high throughput network services. However, our fine-grained experimental analysis reveals that existing congestion control mechanisms still have performance limitations due to inappropriate congestion notifications and the long congestion feedback cycle. In this paper, we propose Mercury, which is an accurate and fast congestion feedback mechanism. Mercury comprises two key components: (1) the state-driven congestion detection and (2) the window-based congestion notification. Specifically, the state-driven congestion detection monitors the queue length and the number of packets received at the switch egress port when the PFC is triggered. It determines the states of egress ports and identifies flows that really contribute to congestion. Then, window-based congestion notification calculates the window sizes for congested flows and rapidly returns Congestion Notification Packets (CNPs) with the window information to the sender. It facilitates the rate adjustment of congested flows. Mercury is compatible with existing RDMA CC mechanisms and can be easily implemented in switches. We employ real-world data sets and conduct both micro-benchmark and large-scale simulations to evaluate the performance of Mercury. The results indicate that, thanks to the accurate and fast congestion feedback, Mercury achieves a reduction in the 99th tail flow completion time by up to 45.1%, 41.8%, 38.7%, 30.9%, and 37.9% compared with Timely, DCQCN, DCQCN+TCD, PACC, and HPCC, respectively.

Abstract Rapid urbanization has reformed the peripheries of China’s main cities during the last four decades. The rural areas have been constantly developed through infrastructure development in recent days which introduces a newly semi-urban region referred to as Desakota. The purpose of this research is to discover potential influencing factors of housing construction technology in desakotas of China which needs to be assessed for the implementation of Desakotas forming globally. In this study, a total of six key primary factors and twenty key secondary factors have been shortlisted, which were surveyed by 120 respondents. After the statistical analysis, it is seen that one primary factor, “Architectural and engineering mechanical factors” has been ranked top. Moreover, “Cost, financial and economic evaluation and Analysis of the impact of the natural environment on buildings” both ranked top among twenty secondary factors. This study adds to the body of knowledge by revealing the primary contributing elements for the first time that need to be taken into consideration in the rural and town communities of desakotas in China. The study results could help stakeholders, construction firms, academicians, researchers, and the government to focus their efforts and resources on the significant changes in the Desakotas in preparation for rapid urban development.

Sacrificial metallic coatings are an effective strategy for mitigating corrosion in steel operating in industrial environments. This review article focuses on examining the protection mechanism of zinc-aluminum-magnesium (Zn-Al-Mg) coatings on steel substrates. Specifically, it investigates the effects of various elements and their corrosion products on the corrosion resistance of Zn-Al-Mg coatings. Furthermore, this review summarizes the formation mechanisms of various specialized corrosion modes that occur following the corrosion of Zn-Al-Mg coatings, based on previous experimental findings. It also includes suggestions for further research areas that could contribute to the development of highly corrosion-resistant and long-lasting coatings. These suggestions are based on published laboratory and field test results available in literature.

Multi-level chemical-structural heterogeneities extensively exist in additively manufactured (AM) metals due to the intrinsic layer-by-layer non-equilibrium solidification process. Strategies designed with particular metastable substructures aiming at advanced performances are significant for AM counterparts. In this work, Si and Mo additions are conducted based on the regulations of dislocation cell substructures and stacking fault energies for stainless steel (SS) 316L fabricated by laser powder bed fusion (PBF-LB). Their load-bearing performance and corrosion behavior are characterized. Results show that additional Mo segregation at cellular boundaries contributes a stronger strengthening effect than Si, which periodically hinders dislocation slip during deformation. Addition of Si triggers deformation twinning at an early stage due to decreased stacking fault energy, and subsequent dynamic Hall-Petch effects improve strain-hardening capability and plasticity for PBF-LB SS 316L+Si. Meanwhile, addition of Mo enhances pitting corrosion resistance of PBF-LB 316L+Mo SS in chloride-containing solutions, especially the pitting re-passivation, which is opposite in the Si addition case due to the increased quantiy of undesired Si/Mn-rich oxides. Underlying deformation and corrosion mechanisms for Mo/Si-added PBF-LB SSs are discussed. Our work is anticipated to motivate the alloy design concept based on particular metastable substructures for advanced AM alloys.

Abstract Background This study aims to compare the clinical effects of two distinct surgical approaches, namely 3D printing-assisted extracorporeal pre-fenestration and Castor integrated branch stent techniques, in treating patients with Stanford type B aortic dissections (TBAD) characterized by inadequate proximal landing zones. Methods A retrospective analysis was conducted on 84 patients with type B aortic dissection (TBAD) who underwent thoracic endovascular aortic repair (TEVAR) with left subclavian artery (LSA) reconstruction at our center from January 2022 to July 2023. Based on the different surgical approaches, the patients were divided into two groups: the group assisted by 3D printing for extracorporeal pre-fenestration (n = 44) and the group using the castor integrated branch stent (n = 40). Clinical indicators: including general patient information, operative time, surgical success rate, intraoperative and postoperative complication rates, re-intervention rate, and mortality, as well as postoperative aortic remodeling, were compared between the two groups. The endpoint of this study is the post-TEVAR mortality rate in patients. Results The surgical success rate and device deployment success rate were 100% in both groups, with no statistically significant difference (P > 0.05). However, the group assisted by 3D printing for extracorporeal pre-fenestration had a significantly longer operative time (184.20 ± 54.857 min) compared to the group using the castor integrated branch stent (152.75 ± 33.068 min), with a statistically significant difference (t = 3.215, p = 0.002, P 0.05). Notably, computed tomography angiography images revealed the expansion of the vascular true lumen and the reduction of the false lumen at three specified levels of the thoracic aorta. The follow-up duration did not show any statistically significant difference between the two groups (10.59 ± 4.52 vs. 9.08 ± 4.35 months, t = 1.561, p = 0.122 > 0.05). Throughout the follow-up period, neither group experienced new endoleaks, spinal cord injuries, nor limb ischemia. In the castor-integrated branch stent group, one patient developed a new distal dissection, prompting further follow-up. Additionally, there was one case of mortality due to COVID-19 in each group. There were no statistically significant differences between the two groups in terms of re-intervention rate and survival rate (P > 0.05). Conclusion Both 3D printing-assisted extracorporeal pre-fenestration TEVAR and castor-integrated branch stent techniques demonstrate good safety and efficacy in treating Stanford type B aortic dissection with inadequate proximal anchoring. The 3D printing-assisted extracorporeal pre-fenestration TEVAR technique has a lower incidence of postoperative cerebral infarction and beak sign, while the castor-integrated branch stent technique has advantages in operative time.

Abstract Patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) often exhibit limited responses to traditional chemotherapy, resulting in poor prognosis. The combination of venetoclax (VEN) with hypomethylating agents has been established as the standard treatment for elderly or medically unfit AML patients unable to undergo intensive chemotherapy. Despite this, the availability of novel VEN-based therapies specifically tailored for those with R/R AML remains scarce. Here, we provide a comprehensive overview of the latest data presented at the 65th American Society of Hematology Annual Meeting, shedding light on the progress and efficacy of VEN-based therapies for R/R AML.

Abstract Background The primary objective of rapeseed breeding is to enhance oil content, which is predominantly influenced by environmental factors. However, the molecular mechanisms underlying the impact of these environmental factors on oil accumulation remain inadequately elucidated. In this study, we used transcriptome data from two higher (HOC) and two lower oil content (LOC) inbred lines at 35 days after pollination (DAP) to investigate genes exhibiting stable expression across three different environments. Meanwhile, a genome-wide association study (GWAS) was utilized to detect candidate genes exhibiting significant associations with seed oil content across three distinct environments. Results The study found a total of 405 stable differentially expressed genes (DEGs), including 25 involved in lipid/fatty acid metabolism and 14 classified as transcription factors. Among these genes, BnBZIP10-A09, BnMYB61-A06, BnAPA1-A08, BnPAS2-A10, BnLCAT3-C05 and BnKASIII-C09 were also found to exhibit significant associations with oil content across multiple different environments based on GWAS of 50 re-sequenced semi-winter rapeseed inbred lines and previously reported intervals. Otherwise, we revealed the presence of additive effects among BnBZIP10-A09, BnKASIII-C09, BnPAS2-A10 and BnAPA1-A08, resulting in a significant increase in seed oil content. Meanwhile, the majority of these stable DEGs are interconnected either directly or indirectly through co-expression network analysis, thereby giving rise to an elaborate molecular network implicated in the potential regulation of seed oil accumulation and stability. Conclusions The combination of transcription and GWAS revealed that natural variation in six environment-insensitive gene regions exhibited significant correlations with seed oil content phenotypes. These results provide important molecular marker information for us to further improve oil content accumulation and stability in rapeseed.

Abstract Lithium- and manganese-rich layered oxide cathode materials have attracted extensive interest because of their high energy density. However, the rapid capacity fading and serve voltage decay over cycling make the waste management and recycling of key components indispensable. Herein, we report a facile concentrated solar radiation strategy for the direct recycling of Lithium- and manganese-rich cathodes, which enables the recovery of capacity and effectively improves its electrochemical stability. The phase change from layered to spinel on the particle surface and metastable state structure of cycled material provides the precondition for photocatalytic reaction and thermal reconstruction during concentrated solar radiation processing. The inducement of partial inverse spinel phase is identified after concentrated solar radiation treatment, which strongly enhances the redox activity of transition metal cations and oxygen anion, and reversibility of lattice structure. This study sheds new light on the reparation of spent cathode materials and designing high-performance compositions to mitigate structural degradation.

Abstract Excited states are essential to many chemical processes in photosynthesis, solar cells, light-emitting diodes, and so on, yet how to formulate, quantify, and predict physiochemical properties for excited states from the theoretical perspective is far from being established. In this work, we leverage the four density-based frameworks from density functional theory (DFT) including orbital-free DFT, conceptual DFT, information-theoretic approach and direct use of density associated descriptors and apply them to the lowest singlet and triplet excited states for a variety of molecular systems to examine their stability, bonding, and reactivity propensities. Our results from the present study elucidate that it is feasible to employ these density-based frameworks to appreciate physiochemical properties for excited states and that excited state propensities can be markedly different from, sometime completely opposite to, those in the ground state. This work is the first effort, to the best of our knowledge, utilizing density-based reactivity frameworks to excited state. It should offer ample opportunities in the future to deal with real-world problems in photophysical and photochemical processes and transformations. Graphical Abstract

Abstract Background Metastasis is one of the leading cause contributes to treatment failure and poor prognosis of hepatocellular carcinoma (HCC) patients. The underlying mechanism of HCC metastasis remains to be determined. Although several RNA binding proteins (RBPs) have been found to participate in tumorigenesis and progression of liver cancer, the role of RBPs in HCC patients with extrahepatic metastases is poorly understood. Methods By performing RNA-seq of primary HCC tissues (including HCC with extrahepatic metastasis and those did not develop metastasis), we identified a set of HCC metastasis-associated RBPs candidates. Among which, ribosomal protein S7 (RPS7) was found to be remarkably increased in HCC tissues and be strongly related to HCC poor survival. Overexpression or CRISPR-Cas9–mediated knockout were applied to investigate the role of RPS7 on the metastasis-associated phenotypes of HCC cells. RNA sequencing, RIP, RNA-pull down, dual luciferase reporter assay, nascent RNA capture assay, and RNA decay and so on, were applied to reveal the underlying mechanism of RPS7 induced HCC metastasis. Results Gain- and loss- of function analyses revealed that RPS7 promoted HCC cells adhesion, migration and invasion capabilities, as well as lung metastasis. Mechanistically, we uncovered that lysyl oxidase-like 2 (LOXL2) was a critical downstream target of RPS7. RPS7 could stabilize LOXL2 mRNA by binding to AUUUA motifs in the 3155–3375 region of the 3’UTR of LOXL2 mRNA, thus increased LOXL2 expression via elevating LOXL2 mRNA abundance. Further research revealed that LOXL2 could accelerate focal adhesion formation through maintaining the protein stability of ITGB1 and activating ITGB1-mediated FAK/SRC signaling pathway, and thereby contribute to the pro-metastasis effect of RPS7. Conclusions Taken together, our data reveal a novel function of RPS7 in HCC metastasis, also reveal the critical roles of the RPS7/LOXL2/ITGB1 axis in HCC metastasis and shed new light on the exploration of molecular drugs against HCC.

This paper proposes a scheme to integrate data communication, wireless energy harvesting and anti-eavesdropping functions into a hybrid beamforming downlink system to satisfy the demand for expanded functionalities in a communication system. To solve this difficult nonconvex problem, the Semidefinite Relaxation (SDR) method is employed to obtain the digital transmitter, the SDR method and penalty convex-concave procedure (CCP) method are employed to obtain the analog transmitter. Simulation results shows four conclusions about the system. Firstly, the larger the SINR target or the energy harvest target, the more transmit power is required. Secondly, the lower the data rate obtained by the eavesdropper, the more transmit power is required. Thirdly, the SDR method and the penalty CCP method complement each other. Finally, the transmit power can be reduced by increasing the number of RF chains or transmit antennas.

Abstract Viruses, as opportunistic intracellular parasites, hijack the cellular machinery of host cells to support their survival and propagation. Numerous viral proteins are subjected to host-mediated post-translational modifications. Here, we demonstrate that the SARS-CoV-2 nucleocapsid protein (SARS2-NP) is SUMOylated on the lysine 65 residue, which efficiently mediates SARS2-NP’s ability in homo-oligomerization, RNA association, liquid-liquid phase separation (LLPS). Thereby the innate antiviral immune response is suppressed robustly. These roles can be achieved through intermolecular association between SUMO conjugation and a newly identified SUMO-interacting motif in SARS2-NP. Importantly, the widespread SARS2-NP R203K mutation gains a novel site of SUMOylation which further increases SARS2-NP’s LLPS and immunosuppression. Notably, the SUMO E3 ligase TRIM28 is responsible for catalyzing SARS2-NP SUMOylation. An interfering peptide targeting the TRIM28 and SARS2-NP interaction was screened out to block SARS2-NP SUMOylation and LLPS, and consequently inhibit SARS-CoV-2 replication and rescue innate antiviral immunity. Collectively, these data support SARS2-NP SUMOylation is critical for SARS-CoV-2 virulence, and therefore provide a strategy to antagonize SARS-CoV-2.

Abstract Background Major depressive disorder (MDD) is a common but severe psychiatric illness characterized by depressive mood and diminished interest. Both nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 1 (NLRP1) inflammasome and autophagy have been reported to implicate in the pathological processes of depression. However, the mechanistic interplay between NLRP1 inflammasome, autophagy, and depression is still poorly known. Methods Animal model of depression was established by chronic social defeat stress (CSDS). Depressive-like behaviors were determined by social interaction test (SIT), sucrose preference test (SPT), open field test (OFT), forced swim test (FST), and tail-suspension test (TST). The protein expression levels of NLRP1 inflammasome complexes, pro-inflammatory cytokines, phosphorylated-phosphatidylinositol 3-kinase (p-PI3K)/PI3K, phosphorylated-AKT (p-AKT)/AKT, phosphorylated-mechanistic target of rapamycin (p-mTOR)/mTOR, brain-derived neurotrophic factor (BDNF), phosphorylated-tyrosine kinase receptor B (p-TrkB)/TrkB, Bcl-2-associated X protein (Bax)/B-cell lymphoma-2 (Bcl2) and cleaved cysteinyl aspartate-specific proteinase-3 (caspase-3) were examined by western blotting. The mRNA expression levels of pro-inflammatory cytokines were tested by quantitative real-time PCR. The interaction between proteins was detected by immunofluorescence and coimmunoprecipitation. Neuronal injury was assessed by Nissl staining. The autophagosomes were visualized by transmission electron microscopy. Nlrp1a knockdown was performed using an adeno-associated virus (AAV) vector containing Nlrp1a–shRNA–eGFP infusion. Results CSDS exposure caused a bidirectional change in hippocampal autophagy function, which was activated in the initial period but impaired at the later stage. In addition, CSDS exposure increased the expression levels of hippocampal NLRP1 inflammasome complexes, pro-inflammatory cytokines, p-PI3K, p-AKT and p-mTOR in a time-dependent manner. Interestingly, NLRP1 is immunoprecipitated with mTOR but not PI3K/AKT and CSDS exposure facilitated the immunoprecipitation between them. Hippocampal Nlrp1a knockdown inhibited the activity of PI3K/AKT/mTOR signaling, rescued the impaired autophagy and ameliorated depressive-like behavior induced by CSDS. In addition, rapamycin, an autophagy inducer, abolished NLRP1 inflammasome-driven inflammatory reactions, alleviated depressive-like behavior and exerted a neuroprotective effect. Conclusions Autophagy dysfunction contributes to NLRP1 inflammasome-linked depressive-like behavior in mice and the regulation of autophagy could be a valuable therapeutic strategy for the management of depression.

Elevated intraocular pressure (IOP) is one of the causes of retinal ischemia/reperfusion injury, which results in NLRP3 inflammasome activation and leads to visual damage. Homer1a is reported to play a protective role in neuroinflammation in the cerebrum. However, the effects of Homer1a on NLRP3 inflammasomes in retinal ischemia/reperfusion injury caused by elevated IOP remain unknown. In our study, animal models were constructed using C57BL/6J and Homer1flox/–/Homer1a+/–/Nestin-Cre+/– mice with elevated IOP-induced retinal ischemia/reperfusion injury. For in vitro experiments, the oxygen-glucose deprivation/reperfusion injury model was constructed with Müller cells. We found that Homer1a overexpression ameliorated the decreases in retinal thickness and Müller cell viability after ischemia/reperfusion injury. Furthermore, Homer1a knockdown promoted NF-κB P65Ser536 activation via caspase-8, NF-κB P65 nuclear translocation, NLRP3 inflammasome formation, and the production and processing of interleukin-1β and interleukin-18. The opposite results were observed with Homer1a overexpression. Finally, the combined administration of Homer1a protein and JSH-23 significantly inhibited the reduction in retinal thickness in Homer1flox/–/Homer1a+/–/Nestin-Cre+/– mice and apoptosis in Müller cells after ischemia/reperfusion injury. Taken together, these studies demonstrate that Homer1a exerts protective effects on retinal tissue and Müller cells via the caspase-8/NF-κB P65/NLRP3 pathway after I/R injury.

Abstract The functions of macrophages are governed by distinct polarization phenotypes, which can be categorized as either anti-tumor/M1 type or pro-tumor/M2 type. Glycosylation is known to play a crucial role in various cellular processes, but its influence on macrophage polarization is not well-studied. In this study, we observed a significant decrease in bisecting GlcNAc during M0-M1 polarization, and impaired bisecting GlcNAc was found to drive M0-M1 polarization. Using a glycoproteomics strategy, we identified Lgals3bp as a specific glycoprotein carrying bisecting GlcNAc. A high level of bisecting GlcNAc modification facilitated the degradation of Lgals3bp, while a low level of bisecting GlcNAc stabilized Lgals3bp. Elevated levels of Lgals3bp promoted M1 polarization through the activation of the NF-кB pathway. Conversely, the activated NF-кB pathway significantly repressed the transcription of MGAT3, leading to reduced levels of bisecting GlcNAc modification on Lgals3bp. Overall, our study highlights the impact of glycosylation on macrophage polarization and suggests the potential of engineered macrophages via glycosylated modification. Video Abstract

Background: Mutations in Slc26a2 cause a spectrum of autosomal-recessive chondrodysplasia with a significant and negligible influence on the quality of life. It has been reported that Slc26a2 deficiency triggers the ATF6 branch of the UPR, which may, in turn, activate the negative regulator of the FGFR3 signaling pathway. However, the correlation between the deletion of Slc26a2 and the augmentation of downstream phosphorylation of FGFR3 has not been investigated in vivo. Methods: First, we constructed Slc26a2 and Fgfr3 double knockout mouse lines and observed gross views of the born mice and histological staining of the tibial growth plates. The second approach was to construct tamoxifen-inducible Cre-ERT2 mouse models to replicate SLC26A2-related non-lethal dysplastic conditions. Pharmacological intervention was performed by administering the FGFR3 inhibitor NVP-BGJ398. The effect of NVP-BGJ398 on chondrocytes was assessed by Alcian blue staining, proliferation, apoptosis, and chondrocyte-specific markers and then verified by western blotting for variations in the downstream markers of FGFR3. The growth process was detected using X-rays, micro-CT examination, histomorphometry staining of growth plates, and immunofluorescence. Results: Genetic ablation of Fgfr3 in embryonic Slc26a2-deficient chondrocytes slightly attenuated chondrodysplasia. Subsequently, in the constructed mild dysplasia model, we found that postnatal intervention with Fgfr3 gene in Slc26a2-deficient chondrocytes partially alleviated chondrodysplasia. In chondrocyte assays, NVP-BGJ398 suppressed the defective phenotype of Slc26a2-deficient chondrocytes and restored the phosphorylation downstream of FGFR3 in a concentration-dependent manner. In addition, in vivo experiments showed significant alleviation of impaired chondrocyte differentiation, and micro-CT analysis showed a clear improvement in trabecular bone microarchitectural parameters. Conclusion: Our results suggested that inhibition of FGFR3 signaling pathway overactivation and NVP-BGJ398 has promising therapeutic implications for the development of SLC26A2-related skeletal diseases in humans. The translational potential of this article: Our data provide genetic and pharmacological evidence that targeting FGFR3 signaling via NVP-BGJ398 could be a route for the treatment of SLC26A2-associated skeletal disorders, which promisingly advances translational applications and therapeutic development.