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Abstract Protein aggregation plays key roles in age-related degenerative diseases, but how different proteins coalesce to form inclusions that vary in composition, morphology, molecular dynamics and confer physiological consequences is poorly understood. Here we employ a general reporter based on mutant Hsp104 to identify proteins forming aggregates in human cells under common proteotoxic stress. We identify over 300 proteins that form different inclusions containing subsets of aggregating proteins. In particular, TDP43, implicated in Amyotrophic Lateral Sclerosis (ALS), partitions dynamically between two distinct types of aggregates: stress granule and a previously unknown non-dynamic (solid-like) inclusion at the ER exit sites (ERES). TDP43-ERES co-aggregation is induced by diverse proteotoxic stresses and observed in the motor neurons of ALS patients. Such aggregation causes retention of secretory cargos at ERES and therefore delays ER-to-Golgi transport, providing a link between TDP43 aggregation and compromised cellular function in ALS patients.

Abstract Background Ailanthone (Ail) extracted from medicinal plants has played an anticancer role in multiple cancers, while there is no research about Ail in renal cell carcinoma (RCC). Methods In the present study, we performed CCK-8 and flow cytometry to assess the effect of Ail on cell viability, apoptosis and cycle. We also performed tandem mass tags (TMT)-labeled quantitative proteomic technology and bioinformatic analysis to identify the functional pathway and proteins of Ail in RCC. Results The results showed Ail could inhibit cell viability and induce cell apoptosis. Proteomic profiling identified 1732 differentially expressed proteins in cells treated with Ail, compared to the negative control group. Gene ontology function annotation and Gene Set Enrichment Analysis (GSEA) were performed to identified the involved biological processes, molecular function and pathway. Results of GSEA proved the enrichment of Deps in EZH2 targets. The comparison between Deps and EZH2 co-expressed genes revealed 44 overlapped genes and we identified 4 hub genes (CDC20, CEP55, TOP2A, and UBE2C) associated with RCC progression. The molecular docking study revealed a moderate to tight binding potential of Ail and EZH2, and western blotting showed EZH2 was suppressed after cells treated with Ail. Conclusion Altogether, we identified the anticancer role of Ail in RCC, including inhibition of cell proliferation and induction of apoptosis. The results also screened the key proteins mediate the function of Ail, which have laid a theoretical foundation for elucidating the applications of Ail in clinical research.

Abstract Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by mitochondrial dysfunction and accumulation of alpha-synuclein (α-Syn)-containing protein aggregates known as Lewy bodies (LB). Here, we investigated the entry of α-Syn into mitochondria to cause mitochondrial dysfunction and loss of cellular fitness in vivo. We show that α-Syn expressed in yeast and human cells is constitutively imported into mitochondria. In a transgenic mouse model, the level of endogenous α-Syn accumulation in mitochondria of dopaminergic neurons and microglia increases with age. The imported α-Syn is degraded by conserved mitochondrial proteases, most notably NLN and PITRM1 (Prd1 and Cym1 in yeast, respectively). α-Syn in the mitochondrial matrix that is not degraded interacts with respiratory chain complexes, leading to loss of mitochondrial DNA (mtDNA), mitochondrial membrane potential and cellular fitness decline. Importantly, enhancing mitochondrial proteolysis by increasing levels of specific proteases alleviated these defects in yeast, human cells, and a PD model of mouse primary neurons. Together, our results provide a direct link between α-synuclein-mediated cellular toxicity and its import into mitochondria and reveal potential therapeutic targets for the treatment of α-synucleinopathies.

In subjects with peculiar susceptibility to severe infections by common pyogenic bacteria, mutations of interleukin-1 receptor-associated kinase proteins (IRAK)1 and IRAK4 had been identified. The IRAK kinases function as downstream signal transductors following the activation of pathogen recognition receptors. In two patients with sequential or repeated invasive infections: herpes simplex virus-triggered hemophagocytic lymphohistiocytosis with tuberculosis, and Streptococcus pneumoniae bacteremia with candidemia respectively, novel mutations of IRAK2 were identified. These mutations compromised the capacity to ubiquinate (or functionally modify) the signal adaptor tumor necrosis factor receptor-associated factor 6. The result is impairment of the cytokine tumor necrosis factor-alpha production. This susceptibility to a varied range of pathogens underlines a potential central role played by IRAK2 in mediating host defense in infectious diseases.

Abstract Purpose To explore the clinical value of tumor abnormal protein (TAP) in the diagnosis and prognosis evaluation of prostate cancer. Methods This study enrolled a total of 265 patients who underwent prostate biopsy procedures from December 2017. TAP levels were assayed in their blood samples using a validated TAP testing kit. Comprehensive pathological assessments, including Gleason scores, TNM staging, and AJCC prognosis stages, were conducted on prostate cancer patients. Further analysis was carried out to examine the correlation between TAP expression levels and various clinical characteristics. Results A significantly elevated TAP concentration was discerned in prostate cancer patients relative to those with benign prostate hyperplasia. Moreover, a significantly elevated TAP expression was detected in prostate cancer patients with high Gleason score (≥ 8) and advanced stages (III and IV), as compared to those with Gleason scores of 6 and 7 and lower stages (I and II). When diagnosing prostate cancer in gray area of PSA, TAP demonstrated superior diagnostic capabilities over PSA alone, with higher diagnostic sensitivity, specificity and accuracy than fPSA/tPSA ratio. Additionally, post-surgical or hormonal treatment, there was a marked reduction in TAP expression level among prostate cancer patients. Conclusion The assessment of TAP presents itself as a promising tool for early diagnosis and holds potential for sensitivity in monitoring treatment reponse in prostate cancer patients.

Abstract Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne viral disease caused by the SFTS virus (Dabie bandavirus), which has become a substantial risk to public health. No specific treatment is available now, that calls for an effective vaccine. Given this, we aimed to develop a multi-epitope DNA vaccine through the help of bioinformatics. The final DNA vaccine was inserted into a special plasmid vector pVAX1, consisting of CD8+ T cell epitopes, CD4+ T cell epitopes and B cell epitopes (six epitopes each) screened from four genome-encoded proteins——nuclear protein (NP), glycoprotein (GP), RNA-dependent RNA polymerase (RdRp), as well as nonstructural protein (NSs). To ascertain if the predicted structure would be stable and successful in preventing infection, an immunological simulation was run on it. In conclusion, we designed a multi-epitope DNA vaccine that is expected to be effective against Dabie bandavirus, but in vivo trials are needed to verify this claim.

Abstract Background Traditional process for clinically significant prostate cancer (csPCA) diagnosis relies on invasive biopsy and may bring pain and complications. Radiomic features of magnetic resonance imaging MRI and methylation of the PRKY promoter were found to be associated with prostate cancer. Methods Fifty-four Patients who underwent prostate biopsy or photoselective vaporization of the prostate (PVP) from 2022 to 2023 were selected for this study, and their clinical data, blood samples and MRI images were obtained before the operation. Methylation level of two PRKY promoter sites, cg05618150 and cg05163709, were tested through bisulfite sequencing PCR (BSP). The PI-RADS score of each patient was estimated and the region of interest (ROI) was delineated by 2 experienced radiologists. After being extracted by a plug-in of 3D-slicer, radiomic features were selected through LASSCO regression and t-test. Selected radiomic features, methylation levels and clinical data were used for model construction through the random forest (RF) algorithm, and the predictive efficiency was analyzed by the area under the receiver operation characteristic (ROC) curve (AUC). Results Methylation level of the site, cg05618150, was observed to be associated with prostate cancer, for which the AUC was 0.74. The AUC of T2WI in csPCA prediction was 0.84, which was higher than that of the apparent diffusion coefficient ADC (AUC = 0.81). The model combined with T2WI and clinical data reached an AUC of 0.94. The AUC of the T2WI-clinic-methylation-combined model was 0.97, which was greater than that of the model combined with the PI-RADS score, clinical data and PRKY promoter methylation levels (AUC = 0.86). Conclusions The model combining with radiomic features, clinical data and PRKY promoter methylation levels based on machine learning had high predictive efficiency in csPCA diagnosis.

Abstract The development of advanced materials capable of autonomous self-healing and mechanical stimulus sensing in aquatic environments holds great promise for applications in underwater soft electronics, underwater robotics, and water-resistant human-machine interfaces. However, achieving superior autonomous self-healing properties and effective sensing simultaneously in an aquatic environment is rarely feasible. Here, we present an ultrafast underwater molecularly engineered self-healing piezo-ionic elastomer inspired by the cephalopod’s suckers, which possess self-healing properties and mechanosensitive ion channels. Through strategic engineering of hydrophobic C–F groups, hydrolytic boronate ester bonds, and ions, the material achieves outstanding self-healing efficiencies, with speeds of 94.5% (9.1 µm/min) in air and 89.6% (13.3 µm/min) underwater, coupled with remarkable pressure sensitivity (18.1 kPa–1) for sensing performance. Furthermore, integration of this mechanosensitive device into an underwater submarine for signal transmission and light emitting diode modulation demonstrates its potential for underwater robotics and smarter human-machine interactions.

The interplay between immune components and the epithelium plays a crucial role in the development and progression of head and neck squamous cell carcinoma (HNSCC). Natural killer (NK) cells, one of the main tumor-killing immune cell populations, have received increasing attention in HNSCC immunotherapy. In this review, we explore the mechanism underlying the interplay between NK cells and HNSCC. A series of immune evasion strategies utilized by cancer cells restrict HNSCC infiltration of NK cells. Overcoming these limitations can fully exploit the antineoplastic potential of NK cells. We also investigated the tumor-killing efficacy of NK cell-based immunotherapies, immunotherapeutic strategies, and new results from clinical trials. Notably, cetuximab, the most essential component of NK cell-based immunotherapy, inhibits the epidermal growth factor receptor (EGFR) signaling pathway and activates the immune system in conjunction with NK cells, inducing innate effector functions and improving patient prognosis. In addition, we compiled information on other areas for the improvement of patient prognosis using anti-EGFR receptor-based monoclonal antibody drugs and the underlying mechanisms and prognoses of new immunotherapeutic strategies for the treatment of HNSCC.

Molecular chaperons stabilize protein folding and play a vital role in maintaining tissue homeostasis. To this intent, mitochondrial molecular chaperons may be involved in the regulation of oxidative phosphorylation and apoptosis during stress events such as infections. However, specific human infectious diseases relatable to defects in molecular chaperons have yet to be identified. To this end, we performed whole exome sequencing and functional immune assessment in a previously healthy Asian female, who experienced severe respiratory failure due to Pneumocystis jiroveci pneumonia and non-HIV-related CD4 lymphocytopenia. This revealed that a chaperon, the mitochondrial paralog of HSP90, TRAP1, may have been involved in the patient’s susceptibility to an opportunistic infection. Two rare heterozygous variants in TRAP1, E93Q, and A64T were detected. The patient’s peripheral blood mononuclear cells displayed diminished TRAP1 expression, but had increased active, cleaved caspase-3, caspase-7, and elevated IL-1β production. Transfection of A64T and E93Q variants in cell lines yielded decreased TRAP1 compared to transfected wildtype TRAP1 and re-capitulated the immunotypic phenotype of enhanced caspase-3 and caspase-7 activity. When infected with live P. jiroveci, the E93Q or A64T TRAP1 mutant expressing cells also exhibited reduced viability. Patient cells and cell lines transfected with the TRAP1 E93Q/A64T mutants had impaired respiration, glycolysis, and increased ROS production. Of note, co-expression of E93Q/A64T double mutants caused more functional aberration than either mutant singly. Taken together, our study uncovered a previously unrecognized role of TRAP1 in CD4+ lymphocytopenia, conferring susceptibility to opportunistic infections.

ObjectiveMeige syndrome (MS) is an adult-onset segmental dystonia for which no satisfactory remedy currently exists. Our team developed a novel surgical approach called bilateral trigeminal/facial nerve combing (BTFC). This study aimed to evaluate the outcomes of patients who underwent BFTC (Clinical Trial Registry Number: ChiCTR2000033481).MethodWe assigned 22 patients with MS to undergo BTFC. The primary outcome was assessed using the movement subscale of the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS-M) at 12 months postoperatively. The second outcome was evaluated using the Medical Outcome Study (MOS) 36-item Short Form Health Survey (SF-36), the dysfunction subscale of the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS-D), and the sub-item scores of the BFMDRS-M. Safety outcomes included the House-Brackmann (HB) functional grading score and the visual analog scale (VAS) for facial numbness.ResultsAt the final follow-up at 12 months, the BFMDRS-M showed a mean improvement of 70.7% from baseline. Mean scores of the BFMDRS-M sub-motor (including the eyes, mouth, and speech/swallowing) improved by 65.6, 81.00, and 60%, respectively. The median score of the total BFMDRS-D score was 0.70 ± 1.17 compared with 1.86 ± 2.21 at baseline. There were no serious operative complications in this population. The quality of life of the patients significantly improved (P < 0.05).ConclusionBFTC has proven to be effective in relieving the symptoms of Meige syndrome. This novel surgical approach offers a new alternative treatment for patients who have failed to respond to medications, botulinum toxin injections, and deep brain stimulation (DBS).Clinical Trial Registrationhttps://www.chictr.org.cn/bin/project/edit?pid=54567, ChiCTR2000033481.

Objective: The present study aimed to explore the function of human bone marrow mesenchymal stem cells (hBMMSCs)-derived exosomal long noncoding RNA histocompatibility leukocyte antigen complex P5 (HCP5) in the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) to improve chronic periodontitis (CP). Methods: Exosomes were extracted from hBMMSCs. Alizarin red S staining was used to detect mineralised nodules. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to measure HCP5 and miR-24-3p expression. The mRNA and protein levels of alkaline phosphatase (ALP), osteocalcin, osterix, runt-related transcription factor 2, bone morphogenetic protein 2, osteopontin, fibronectin, collagen 1, heme oxygenase 1 (HO1), P38, and ETS transcription factor ELK1 (ELK1) were detected using RT-qPCR and Western blot. Enzyme-linked immunosorbent assay (ELISA) kits were used to determine the HO1 and carbon monoxide concentrations. Heme, biliverdin, and Fe2+ levels were determined using detection kits. Micro-computed tomography, hematoxylin and eosin staining, ALP staining, tartrate-resistant acid phosphatase staining, ELISA, and RT-qPCR were conducted to evaluate the effect of HCP5 on CP mice. Dual luciferase, RNA immunoprecipitation, and RNA pulldown experiments were performed to identify the interactions among HCP5, miR-24-3p, and HO1. Results: The osteogenic ability of hPDLSCs significantly increased when co-cultured with hBMMSCs or hBMMSCs exosomes. Overexpression of HCP5 and HO1 in hBMMSCs exosomes promoted the osteogenic differentiation of hPDLSCs, and knockdown of HCP5 repressed the osteogenic differentiation of hPDLSCs. HCP5 knockdown enhanced the inflammatory response and repressed osteogenesis in CP mice. MiR-24-3p overexpression diminished the stimulatory effect of HCP5 on the osteogenic ability of hPDLSCs. Mechanistically, HCP5 acted as a sponge for miR-24-3p and regulated HO1 expression, and HO1 activated the P38/ELK1 pathway. Conclusion: HBMMSCs-derived exosomal HCP5 promotes the osteogenic differentiation of hPDLSCs and alleviates CP by regulating the miR-24-3p/HO1/P38/ELK1 signalling pathway.

Mitochondria are the cellular energy hub and central target of metabolic regulation. Mitochondria also facilitate proteostasis through pathways such as the ‘mitochondria as guardian in cytosol’ (MAGIC) whereby cytosolic misfolded proteins (MPs) are imported into and degraded inside mitochondria. In this study, a genome-wide screen in Saccharomyces cerevisiae uncovered that Snf1, the yeast AMP-activated protein kinase (AMPK), inhibits the import of MPs into mitochondria while promoting mitochondrial biogenesis under glucose starvation. We show that this inhibition requires a downstream transcription factor regulating mitochondrial gene expression and is likely to be conferred through substrate competition and mitochondrial import channel selectivity. We further show that Snf1/AMPK activation protects mitochondrial fitness in yeast and human cells under stress induced by MPs such as those associated with neurodegenerative diseases.

Due to the superior physical properties and high-level alignment of the nanoscale building blocks, assembly of high-quality two-dimensional (2D) nanosheets into macroscopic engineering structure materials can achieve many unexpected performance. Natural mica nanosheets (MNSs) are abundant and with superlative properties, showing huge prospect for engineering structural materials. However, the difficulty of the mass production with large size and high aspect ratio are the current factors that limit this. Inspired by the well-known scotch-tape exfoliation, herein we develop a gummy-tape exfoliation (GTE) method by using liquid oligomers as mediums in ball-milling process to massively produce large-size and ultrathin MNSs. As a confirmation, the obtained MNSs show a record high aspect ratio of ≈1320 and a large actual yield of ∼ 80 %. A transparent biobased aromatic polyester nanocomposite film made of such MNSs and polyethylene furandicarboxylate (PEF) matrix possesses remarkably improved mechanical, barrier properties, and UV-shielding performances at an extremely low filler loading (≤0.5 vol%), making it a novel potential engineering material for packing fields in foods, drugs, and electronic products, etc.

Improving the heat resistance of bio-based and biodegradable polyesters is of great significance to extend their applications. Herein, N,N’-trans-1,4-cyclohexane-bis(pyrrolidone-4-methyl carboxylate) (T-CBPMC) was prepared through efficient Michael-addition reaction between dimethyl itaconate and trans-1,4-cyclohexanediamine. The obtained T-CBPMC was copolymerized into aliphatic poly(butylene succinate) (PBS), and a series of PBSPs copolymers with T-CBPMC (BP) molar percentages between 41−80 mol % and weight average molecular weight (Mw) values ranging between 5.77*104 and 6.67*104 g/mol were prepared. BP units efficiently facilitated the melting temperature (203-251 °C) and isothermal-crystallization rate (t1/2 < 20 s) of PBSPs, endowing the highest heat resistance among commercial biodegradable polyesters, which helps maintain stable in pasteurization, high-temperature disinfection, and microwave environments. Moreover, these copolymers displayed remarkable mechanical, gas barrier properties and degradability. PBSP40-PBSP60 obtained high elastic modulus (335–872 MPa) and tensile strength (24.7–31.5 MPa), and good toughness simultaneously. Multiple-ring structures and large steric hindrance of BP units resulted in superior O2 barrier performance than that of non-degradable PET films. Importantly, the PBSP copolyesters showed obvious degradation in water environments and relatively better enzymatic degradation. It was interesting to find that even with 70 % of the BP units, the PBSP copolyesters still retained hydrolysis ability. The resulting PBSP copolyesters open the way for alternative candidates of biodegradable packaging materials with rapid crystallization, high heat-resistance and gas barrier.

Despite the importance of interregional skilled migration to regional development, few studies have explored its spatial spillover effects and their changes over time. Thus, employing the Spatial Durbin Model, we investigate the presence of regional spillovers of skilled migration at both national and sub-national levels in China. Especially, we focus on the regional difference and change in the spatial spillover. Although our results confirm positive spillover effects at the national level due to the strong mobility characteristic of skilled migrants, developed regions benefit more from spillovers of skilled migration than developing regions, and such effects are divergent in different regions over time. Our findings also indicate that changes in spatial spillovers among regions are closely associated with the mobility of economic factors in geography. Theoretically, by considering the spatial effects of skilled migration on the innovation output of recipient regions, we extend the labour economics literature into geographical economic agglomeration, especially innovation economic geography. Methodologically, we examine the spatial effects at both national and sub-national levels, and capture the spatial externalities; we also apply Maximum Likelihood estimation to assess the endogeneity issues to understand the mechanisms of spillover change over time. The study can be of significance for municipalities in the policy-making of attracting talents and promoting regional innovation.

Abstract Proper differentiation of corneal epithelial cells (CECs) from limbal stem/progenitor cells (LSCs) is required for maintenance of ocular homeostasis and clear vision. Here, using a single-cell transcriptomic atlas, we delineate the comprehensive and refined molecular regulatory dynamics during human CEC development and differentiation. We find that RORA is a CEC-specific molecular switch that initiates and drives LSCs to differentiate into mature CECs by activating PITX1. RORA dictates CEC differentiation by establishing CEC-specific enhancers and chromatin interactions between CEC gene promoters and distal regulatory elements. Conversely, RORA silences LSC-specific promoters and disrupts promoter-anchored chromatin loops to turn off LSC genes. Collectively, our work provides detailed and comprehensive insights into the transcriptional dynamics and RORA-mediated epigenetic remodeling underlying human corneal epithelial differentiation.

Abstract Purpose This research was conducted to investigate the potential of short-chain fatty acids (SCFAs) in protecting organs from heat stress-induced injuries and gut microbiota modulation. Methods Sprague–Dawley rats were randomly assigned to various groups including a control group, a room temperature training group, a hyperthermia training group, SCFAs pretreatment group, and recipients received feces from the HT group. After strenuous training at high temperatures, the levels of plasma enzymes AST, ALT, BUN, and Cr were evaluated. The changes in gut microbiota and fecal metabolites were detected using 16S rRNA sequencing and GC–MS methods. Pathological examination of colon and liver tissues was conducted, and immunohistochemical techniques were employed to assess intestinal barrier function. Results The findings indicate that SCFAs hold the potential for mitigating liver and colon damage caused by heat stress. With the intervention of SCFAs, there were observable changes in the structure and metabolites of the intestinal microbiota, as well as improvements in intestinal barrier function. Further support for the benefits of SCFAs was found through fecal microbiota transplantation, which demonstrated that modified gut microbiota can effectively reduce organ damage. Conclusions This study provides evidence that SCFAs, as metabolites of the gut microbiota, have a valuable role to play in regulating gut health and mitigating the harmful effects of heat stress.

Objectives Scaphoid nonunion remains a challenging problem to manage with no general consensus on its treatment recommendations. We propose a novel minimally invasive (MIS) technique of arthroscopic bone grafting (ABG) with robot‐assisted fixation for the treatment of scaphoid nonunions. Methods Patients with radiographically proven scaphoid nonunion treated by this novel surgical technique were included. Following arthroscopic debridement and iliac crest bone grafting, the scaphoid was fixed percutaneously using either multiple Kirschner (K)‐wires or a headless compression screw using a robotic navigation system. Results Six male patients with an average age of 29.2 years were enrolled. Four patients had scaphoid waist fractures, and the other two were proximal pole fractures. During wrist arthroscopy, punctate bleeding of the proximal scaphoid fragment was observed in four out of the six patients. Half of the patients were fixed using a headless compression screw and the other half using multiple K‐wires. All the guidewires were placed with a single‐attempt using the robotic navigation system. Postoperatively, all the scaphoid fractures had complete radiographic union by 16 weeks. At a mean follow‐up of 18.3 months, there were significant improvements in wrist range of motion, grip strength, and patient‐rated outcomes. No intraoperative or early postoperative complications were encountered in any of our patients. Conclusion Arthroscopic bone grafting with robot‐assisted fixation is a feasible and promising therapeutic option for scaphoid nonunions, regardless of the vascularity of the proximal pole fragment. This novel technique allows for anatomic restoration of the scaphoid alignment and accurate, targeted placement of implants into the scaphoid nonunion site within a single‐attempt using a robotic navigation system.

Limbal epithelial stem/progenitor cells (LESCs) proliferate, migrate and differentiate into mature corneal epithelium cells (CECs) that cover the ocular surface. LESCs play a crucial role in the maintenance and regeneration of the corneal epithelium, and their dysfunction can lead to various corneal diseases. Neuregulin 1 (NRG1) is a member of the epidermal growth factor family that regulates the growth and differentiation of epithelial tissues. Here, we depicted the dynamic transcriptomic profiles during human CEC differentiation, identifying six gene co-expression modules that were specific to different differentiation stages. We found that the expression of NRG1 was high in human LESCs and decreased dramatically upon differentiation. Knockdown of NRG1 significantly inhibited LESC proliferation and upregulated the expression of the terminal differentiation marker genes KRT3, KRT12 and CLU. In addition, the scratch wound closure assay showed that knockdown of NRG1 attenuated wound closure of LESCs over 24 h. Together, we dissected the transcriptional regulatory dynamics during CEC differentiation and identified NRG1 as a key regulator that promoted LESC proliferation and migration and maintained the undifferentiated state.

Polyurethane is an excellent and widely used polymer material. In synthesizing polyurethane, the structure of soft and hard segments in polyurethane could be adjusted, which can obtain better properties than other polymer materials, such as good mechanical properties and biocompatibility. In recent years, due to their excellent chemical stability, biocompatibility, and low cytotoxicity, polyurethanes have been widely used for biomedical applications. To solve the problems of degradation and recycling, the development of bio-based polyurethane has also become a current hot spot. This paper summarizes the research progress and applications of polyurethane materials for dressings, skin sensors, orthopedics, and cardiovascular. It also looks forward to the future development of polyurethane medical materials.

Purpose This study aims to systematically review the efficacy and safety of total ankle replacement (TAR) and ankle fusion (AF) as treatment options for end-stage ankle arthritis. Methods A comprehensive literature search was conducted on data from multiple databases, including PubMed, The Cochrane Library, Construction and Building Materials, Embase, Web of Science, and Scopus for RCTs and prospective cohort studies comparing TAR and AF in patients with end-stage ankle arthritis from inception up to June, 2023. Our primary outcomes of interest included patients’ clinical function scores and complications. We employed Review Manager 5.4 and Stata/MP 14.0 software for the meta-analysis. Results Our analysis incorporated 13 comparative studies, including 11 prospective studies, one pilot RCT, and one RCT. The pooled results revealed no significant difference in postoperative Short Form-36 scores between the TAR and AF groups (MD = −1.19, 95% CI: −3.89 to 1.50, p = .39). However, the postoperative Foot and Ankle Ability Measure scores in the AF group were significantly higher than in the TAR group (MD = 8.30, 95% CI: 1.01–15.60, p = .03). There was no significant difference in postoperative complication rates between the TAR and AF groups (RR = 0.95, 95% CI: 0.59 to 1.54, p = .85). Conclusion Currently available evidence suggests no significant disparity in postoperative outcomes between TAR and AF. In the short term, TAR demonstrates better clinical scores than AF and lower complication rates. Conversely, in the long term, AF exhibits superior clinical scores and lower complication rates, although this difference is not statistically significant.

This study explores the mitigation of cavitation damage in hydraulic engineering through air entrainment. The primary aim is to experimentally analyze the shock wave characteristics emitted by cavitation bubbles adjacent to air bubbles affixed to a tube nozzle. The schlieren optical system is utilized to visualize the shock wave, while a hydrophone measures its pressure. Experiments are conducted on cavitation bubbles induced by the spark-generated method in the vicinity of air bubbles, varying the dimensionless distances and sizes of the air bubbles. The results indicate that (1) The introduction of an air bubble noticeably changes the morphology, kinematic behavior, and shock wave features of the cavitation bubble. (2) Four distinct shock wave patterns are identified based on the quantity and shape of the shock wave, with variations in the cavitation bubble's collapsing behavior and shock wave characteristics across different patterns. (3) The dimensionless distance γ and size δ exert significant influence on the shock wave's quantity, pressure peak, shape, and energy. With γ decreases or δ increases, the shock wave quantity increases while the shock wave intensity decreases. This investigation of the interaction between cavitation bubbles and air bubbles is essential for elucidating the mechanism through which air entrainment mitigates cavitation damage.

The arid inland river basins in northwestern China have been experienced various stages of soil and water resources over-exploitation over the past 50 years, as well as ecological protection and restoration in recent years, which has significantly influenced the regional groundwater and ecological environment. However, the long-term evolution of groundwater and its ecological effects remain unclear. In this study, the Kongque River Basin is chosen as a study area, and the spatio-temporal evolution of groundwater flow field is analyzed based on the comparison of recent groundwater monitoring data and historical data. The ecological effects of long-term groundwater evolution are discussed by analyzing the influence of regional groundwater to Populus euphratica in the riparian zone. The results show that from 1971 to 2021, the groundwater flow in the Kongque River Basin has undergone drastic variation due to excessive groundwater exploitation, and the groundwater levels have shown a general downward trend. The total area where the groundwater levels have decreased by more than 40 m is 204.69 km2, as well as 1735.81 and 1018.56 km2 for 20−40 and 5−20 m, and eventually led to the formation of a regional drawdown funnel, which have seriously affected the water consumption of Populus euphratica in the middle and lower reaches. From 1971 to 2016, the regional groundwater level depth in the riparian zone of the Kongque River Basin decreased by more than 10 m, with a degradation and shrinkage of Populus euphratica. After the implementation of the ecological water transport project since 2016, the groundwater level depth has gradually increased by 2−4 m, and reached the critical groundwater level of Populus euphratica. From 2014 to 2018, the regional NDVI increased by 17%, which indicates that the coverage rate of natural vegetation has improved. This study can improve the understanding of evolution patterns in groundwater and ecological environment in arid inland river basins of the northwestern China, and provide scientific references for sustainable development and utilization of groundwater and ecological protection in similar regions.

Abstract This paper studies an optimization problem of antenna placement for multiple heading angles of the target in a distributed multiple-input multiple-output (MIMO) radar system. An improved method to calculate the system’s coverage area in light of the changing target heading is presented. The antenna placement optimization problem is mathematically modelled as a sequential decision problem for compatibility with reinforcement learning solutions. A reinforcement learning agent is established, which uses the long short-term memory (LSTM)-based proximal policy optimization (PPO) method as the core algorithm to solve the antenna placement problem. Finally, the experimental findings demonstrate that the method can enhance the coverage area of antenna placement and thus has reference value for providing new ideas for the antenna placement optimization of distributed MIMO radar.

As a typical case of the optimal planning for the provision of restricted medical resources, widespread vaccination is considered an effective and sustainable way to prevent and control large-scale novel coronavirus disease 2019 (COVID-19) outbreaks. However, an initial supply shortage of vaccines is inevitable because of the narrow production and logistical capacity. This work focuses on the multi-type vaccine resource allocation problem in a two-dose vaccination campaign under limited supply. To address this issue, we extended an age-stratified susceptible, exposed, infectious, and recovered (SEIR) epidemiological model to incorporate a two-dose vaccination campaign involving multiple vaccine types to fully characterize the various stages of infection and vaccination. Afterward, we integrated the proposed epidemiological model into a nonlinear programming (NLP) model to determine the optimal allocation strategy under supply capacity and vaccine hesitancy constraints with the goal of minimizing the cumulative number of deaths due to the pandemic over the entire planning horizon. A case study based on real-world data from the initial mass vaccination campaign against COVID-19 in the Midlands, England, was taken to validate the applicability of our model. Then, we performed a comparative study to demonstrate the performance of the proposed method and conducted an extensive sensitivity analysis on critical model parameters. Our results indicate that prioritizing the allocation of vaccines to elderly persons is an effective strategy for reducing COVID-19-related fatalities. Furthermore, we found that vaccination alone will not be sufficient for epidemic control in the short term, and appropriate non-pharmacological interventions are still important for effective viral containment during the initial vaccine rollout. The results also showed that the relative efficacy of the first dose is a vital factor affecting the optimal interval between doses. It is always best to complete the two-dose vaccination schedule as soon as possible when the relative efficacy of the first dose is low. Conversely, delaying the second dose of a vaccine as long as possible to increase the proportion of the population vaccinated with a single dose tends to be more favorable when the relative efficacy of the first dose is high. Finally, our proposed model is general and easily extendable to the study of other infectious disease outbreaks and provides important implications for public health authorities seeking to develop effective vaccine allocation strategies for tackling possible future pandemics.

Detecting small dark targets underwater, such as fishing nets, is critical to the operation of underwater robots. Existing techniques often require more computational resources and operate under harsh underwater imaging conditions when handling such tasks. This study aims to develop a model with low computational resource consumption and high efficiency to improve the detection accuracy of fishing nets for safe and efficient underwater operations. The Light-YOLO model proposed in this paper introduces an attention mechanism based on sparse connectivity and deformable convolution optimized for complex underwater lighting and visual conditions. This novel attention mechanism enhances the detection performance by focusing on the key visual features of fishing nets, while the introduced CoTAttention and SEAM modules further improve the model’s recognition accuracy of fishing nets through deeper feature interactions. The results demonstrate that the proposed Light-YOLO model achieves a precision of 89.3%, a recall of 80.7%, and an mAP@0.5 of 86.7%. Compared to other models, our model has the highest precision for its computational size and is the lightest while maintaining similar accuracy, providing an effective solution for fishing net detection and identification.

Abstract Sphingosine kinases (SphK), including SphK1 and SphK2, are important enzymes promoting progression of prostate cancer. SKI-178 is a novel and highly potent SphK1/2 dual inhibitor. We here tested the potential anti-prostate cancer cell activity of SKI-178. Bioinformatics analyses and results from local tissues demonstrated that that both SphK1 and SphK2 are upregulated in human prostate cancer tissues. Ectopic overexpression of SphK1 and SphK2, by lentiviral constructs, promoted primary prostate cancer cell proliferation and migration. In primary human prostate cancer cells and immortalized cell lines, SKI-178 potently inhibited cell viability, proliferation, cell cycle progression and cell migration, causing robust cell death and apoptosis. SKI-178 impaired mitochondrial functions, causing mitochondrial depolarization, reactive oxygen species production and ATP depletion.SKI-178 potently inhibited SphK activity and induced ceramide production, without affecting SphK1/2 expression in prostate cancer cells. Further, SKI-178 inhibited Akt-mTOR activation and induced JNK activation in prostate cancer cells. Contrarily, a constitutively-active Akt1 construct or the pharmacological JNK inhibitors attenuated SKI-178-induced cytotoxicity in prostate cancer cells. In vivo, daily intraperitoneal injection of a single dose of SKI-178 potently inhibited PC-3 xenograft growth in nude mice. SphK inhibition, ceramide production, ATP depletion and lipid peroxidation as well as Akt-mTOR inactivation and JNK activation were detected in PC-3 xenograft tissues with SKI-178 administration. Together, targeting SphK1/2 by SKI-178 potently inhibited prostate cancer cell growth in vitro and in vivo.

Abstract Purpose To predict the International Neuroblastoma Pathology Classification (INPC) in neuroblastoma using a computed tomography (CT)-based radiomics approach. Methods We enrolled 297 patients with neuroblastoma retrospectively and divided them into a training group (n = 208) and a testing group (n = 89). To balance the classes in the training group, a Synthetic Minority Over-sampling Technique was applied. A logistic regression radiomics model based on the radiomics features after dimensionality reduction was then constructed and validated in both the training and testing groups. To evaluate the diagnostic performance of the radiomics model, the receiver operating characteristic curve and calibration curve were utilized. Moreover, the decision curve analysis to assess the net benefits of the radiomics model at different high-risk thresholds was employed. Results Seventeen radiomics features were used to construct radiomics model. In the training group, radiomics model achieved an area under the curve (AUC), accuracy, sensitivity, and specificity of 0.851 (95% confidence interval (CI) 0.805–0.897), 0.770, 0.694, and 0.847, respectively. In the testing group, radiomics model achieved an AUC, accuracy, sensitivity, and specificity of 0.816 (95% CI 0.725–0.906), 0.787, 0.793, and 0.778, respectively. The calibration curve indicated that the radiomics model was well fitted in both the training and testing groups (p > 0.05). Decision curve analysis further confirmed that the radiomics model performed well at different high-risk thresholds. Conclusion Radiomics analysis of contrast-enhanced CT demonstrates favorable diagnostic capabilities in distinguishing the INPC subgroups of neuroblastoma. Graphical Abstract Critical relevance statement Radiomics features of contrast-enhanced CT images correlate with the International Neuroblastoma Pathology Classification (INPC) of neuroblastoma.

Grafting is the most important means of breeding peach, plum, apricot, and other fruit trees, and the selection of the rootstock is crucial to the quality of the grafting and the yield of the products. The traditional commonly used peach rootstock is susceptible to root-knot nematode infections, resulting in a decreased yield, while a variety of cherry plum rootstocks, Mirabolano 29C, is resistant to root-knot nematode. In this study, root-knot nematode infection experiments on seedlings of traditional peach rootstocks and Mirabolano 29C confirmed that Mirabolano 29C was indeed more resistant to root-knot nematodes. At the same time, we compared the roots of the root-knot nematode uninfected and infected Mirabolano 29C by transcriptome sequencing and found 3 176 differentially expressed genes. A further functional enrichment analysis of these genes found that the secondary metabolites, phenylpropane and flavonoids, may be responsible for the high resistance of Mirabolano 29C to root-knot nematodes. These results can provide a reference value for the disease resistance breeding of rootstocks.

Objective: This study aimed to investigate brain activity changes in patients suffering from neuropathic pain (NP) following brachial plexus avulsion (BPA). Methods: Fifteen patients with NP following BPA and eight healthy participants (HP) were recruited for this study. All participants underwent examination using resting-state functional MRI. The amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) were calculated and compared between the BPA group, left-BPA subgroup, right-BPA subgroup, and the HP group using independent samples t-tests. Results: In the BPA group, there were notable increases in ALFF/ReHo observed in the left rolandic operculum, insula, and supramarginal gyrus, while decreases were observed in the left paracentral lobule, fusiform gyrus, calcarine fissure and surrounding cortex, lingual gyrus, precuneus, as well as the bilateral anterior/median cingulate and paracingulate gyri, supplementary motor area, and cerebellum. In the left-BPA subgroup, elevated ALFF/ReHo levels were identified in the left middle/inferior frontal gyri, rolandic operculum, and supramarginal gyrus, with corresponding decreases in the left calcarine fissure and surrounding cortex, inferior occipital gyrus, fusiform gyrus, lingual gyrus, as well as the bilateral anterior/median cingulate and paracingulate gyri, postcentral gyri, supplementary motor area, paracentral lobules, and cerebellum. The right-BPA subgroup displayed increased ALFF/ReHo in the left frontal lobe, rolandic operculum, insula, fusiform gyrus, and lingual gyrus, as well as the right cerebellum. Conversely, decreases in ALFF/ReHo were observed in the bilateral anterior/median cingulate and paracingulate gyri, calcarine fissure and surrounding cortex, cuneus, and occipital lobes. Conclusions: The NP after BPA caused spontaneous activity changes in brain regions associated with linguistic, visual, somatosensory, and motor coordination and processing function. The majority of these abnormal areas were situated in the left cerebral hemisphere, while the effect of cingulate gyri and cerebellum seemed to be bilateral.

This article presents a DOD-SOH equalization method for a DRB system based on the Deep DQN algorithm. The proposed method utilizes DQN to learn the operational processes of the system. By integrating the advantages of DRB with SOH equalization theory and the DQN algorithm from the perspective of DOD, our method significantly improve battery performance and ensure cell balancing. To begin with, we present a dynamic reconfigurable battery system with a simple topological structure and outline its switching control process. Additionly, we provide an analysis of the SOH balancing principle and elaborate on the control process of DQN algorithm. Finally, subsequent simulations are carried out, and the simulation results demonstrate outstanding performances in reducing the variance of SOHs, which indicates an enhancement in the level of SOH balancing as well.

Summary: Accumulation of protein aggregates is a hallmark of cellular aging and degenerative disorders. This could result from either increased protein misfolding and aggregation or impaired dissolution of aggregates formed under stress, the latter of which is poorly understood. In this study, we employed quantitative live-cell imaging to investigate the dynamic process of protein disaggregation in yeast. We show that protein aggregates formed upon heat stress are solid condensates, but after stress attenuation these protein aggregates first transition into a liquid-like state during their dissolution. This solid-to-liquid phase transition (SLPT) accompanies the reduction in aggregate number due to the fusion of the liquid condensates. The chaperone activity of Hsp104, a Clp/HSP100 family chaperone, is required for both SLPT and subsequent dispersal of the liquid condensates. Sse1, a yeast HSP110 chaperone, also facilitates SLPT. These results illuminate an unexpected mechanistic framework of cellular control over protein disaggregation upon stress attenuation.

A thorough understanding of aerodynamic characteristics of a high-speed train in a bridge–tunnel section is of extremely importance to ensure the vehicle safety of driving. This study presents a numerical investigation on aerodynamic characteristics of a high-speed train travelling through a bridge–tunnel section under non-uniform airflows caused by mountain terrain effect. First, the wind field distribution of the section is obtained from a large-scale numerical simulation model of a mountain terrain. Second, a high-fidelity small-scale model is established to simulate the aerodynamic characteristics. It is validated by the wind tunnel test. Third, the influence of non-uniform wind speeds and wind attack angles airflows on the aerodynamic characteristics are investigated. Finally, a derived empirical equation is introduced to predict the aerodynamic coefficients of the vehicle under non-uniform airflows caused by the mountain terrain. The results demonstrate that due to the effect of mountain terrain, the trend of aerodynamic coefficients varies slowly when the vehicle travels in the bridge–tunnel section. Meanwhile, when the vehicle travels near the tunnel exit, the jumping property of the pressure along the vehicle longitudinal axis is reduced. Furthermore, the predictions of the overturning moment coefficients via the simple empirical equation are consistent with the numerical simulation results.

Polymeric nanofibers are attractive nanomaterials owing to their high surfacearea- to-volume ratio and superior flexibility but designing durable and recyclable polymer nanofibers is challenging. Here, the authors integrate the concept of covalent adaptable networks to produce dynamic covalently crosslinked nanofibers via electrospinning.

Ionizing radiation has its unique popularity as a non-thermal decontamination technique treating with protein-rich foodstuffs to ensure the microbial and sensory quality, particularly for shell eggs. However, the changes in the functional properties of egg protein fractions such as liquid egg white (LEW) with macro/microstructural information are still controversial. Hence, this study was designed to elaborate the foaming and heat-set gelation functionality of LEW following different γ-ray irradiation dose treatments (0, 1, 3 or 5 kGy). For such, the physicochemical properties (active sulfhydryl and the hydrophobicity of protein moieties), structural characteristics (through X-ray diffraction, Fourier-transform infrared spectroscopy and differential scanning calorimetry) and interfacial activities (rheological viscosity, interfacial tension, microrheological performance) were investigated. Then, the thermal gelation of LEW in relation to the texture profile and microstructure (by means of a scanning electron microscope) was evaluated followed by the swelling potency analysis of LEW gel in enzyme-free simulated gastric juice. The results indicated that irradiation significantly increased the hydrophobicity of liquid egg white proteins (LEWPs) (p < 0.05) by exposing non-polar groups and the interfacial rearrangement from a β-sheet to linear and smaller crystal structure, leading to an enhanced foaming capacity. Microstructural analysis revealed that the higher dose irradiation (up to 5 kGy) could promote the proteins’ oxidation of LEW alongside protein aggregates formed in the amorphous region, which favored heat-set gelation. As evidenced in microrheology, ≤3 kGy irradiation provided an improved viscoelastic interface film of LEW during gelatinization. Particularly, the LEW gel treated with 1 kGy irradiation had evident swelling resistance during the times of acidification at pH 1.2. These results gave new insight into the irradiation-assisted enhancement of foaming and heat-set gelation properties of LEW.

Anthropogenic waste deposition in aquatic environments precipitates a decline in water quality, engendering pollution that adversely impacts human health, ecological integrity, and economic endeavors. The evolution of underwater robotic technologies heralds a new era in the timely identification and extraction of submerged litter, offering a proactive measure against the scourge of water pollution. This study introduces a refined YOLOv8-based algorithm tailored for the enhanced detection of small-scale underwater debris, aiming to mitigate the prevalent challenges of high miss and false detection rates in aquatic settings. The research presents the YOLOv8-C2f-Faster-EMA algorithm, which optimizes the backbone, neck layer, and C2f module for underwater characteristics and incorporates an effective attention mechanism. This algorithm improves the accuracy of underwater litter detection while simplifying the computational model. Empirical evidence underscores the superiority of this method over the conventional YOLOv8n framework, manifesting in a significant uplift in detection performance. Notably, the proposed method realized a 6.7% increase in precision (P), a 4.1% surge in recall (R), and a 5% enhancement in mean average precision (mAP). Transcending its foundational utility in marine conservation, this methodology harbors potential for subsequent integration into remote sensing ventures. Such an adaptation could substantially enhance the precision of detection models, particularly in the realm of localized surveillance, thereby broadening the scope of its applicability and impact.

The research domain about the selection and design methodology of battery topology structures for energy storage systems, grounded in practical application scenarios, remains significantly underexplored. Furthermore, a substantial gap exists in the current state of research, where the majority of studies lack a comprehensive analysis of losses and reliability associated with reconfigurable battery topology structures. This paper quantitatively analyzes existing MOSFET-based topologies from three key dimensions: losses, costs, and reliability. The study aims to discern the impact of different topology structures and energy storage systems with redundant units on these three dimensions. Subsequently, while ensuring the adaptability of the topology structure, we propose a novel reconfigurable battery system topology suitable for DC microgrids, accompanied by its corresponding control strategy. Through comparative analysis with three typical topology structures, this topology structure has been validated to exhibit certain advantages in terms of losses, reliability, and costs. Lastly, the feasibility of the introduced topology structure is demonstrated through simulation using MATLAB/Simulink. Simulation results indicate that the proposed topology structure not only provides precise control of charge and discharge currents but also demonstrates excellent battery balancing capabilities.

Abstract NEDD8-conjugating enzymes, E2s, include the well-studied ubiquitin-conjugating enzyme E2 M (UBE2M) and the poorly characterized ubiquitin-conjugating enzyme E2 F (UBE2F). UBE2M and UBE2F have distinct and prominent roles in catalyzing the neddylation of Cullin or non-Cullin substrates. These enzymes are overexpressed in various malignancies, conferring a worse overall survival. Targeting UBE2M to influence tumor growth by either modulating several biological responses of tumor cells (such as DNA-damage response, apoptosis, or senescence) or regulating the anti-tumor immunity holds strong therapeutic potential. Multiple inhibitors that target the interaction between UBE2M and defective cullin neddylation protein 1 (DCN1), a co-E3 for neddylation, exhibit promising anti-tumor effects. By contrast, the potential benefits of targeting UBE2F are still to be explored. It is currently reported to inhibit apoptosis and then induce cell growth; hence, targeting UBE2F serves as an effective chemo-/radiosensitizing strategy by triggering apoptosis. This review highlights the most recent advances in the roles of UBE2M and UBE2F in tumor progression, indicating these E2s as two promising anti-tumor targets.

Sensing properties of the human skin are inspiring for the design of stretchable iontronics but achieving self-healing properties, elasticity and effective control of ion dynamics at the same time is challenging. Here, the Authors report a Cl-functionalized iontronic pressure sensitive material and realize good self-healing properties and mechanosensitive piezo-ionic dynamics.

Abstract Background The American Joint Committee on Cancer (AJCC) 8th staging system of prostate cancer may be insufficient in predicting the prognosis of some staged patients. This study aimed to modify the AJCC 8th staging system in patients with advanced prostate cancer. Methods Data of patients with advanced prostate cancer from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2016 were enrolled in this cohort study. All patients were divided into the training set and the testing set with a ratio of 6:4. Multivariate Cox survival model was utilized to obtain the nomogram score for each stage variable. The modified staging system was based on the total nomogram score. The C-index and Kaplan-Meier (K-M) curves were used to show the prognostic prediction effect of patients with different staging systems. Results A total of 28,006 patients were included for analysis. T stage, N stage, M stage, primary Gleason pattern score, secondary Gleason pattern score, and PSA level were included as stage variables. Patients with AJCC stage III C [hazard ratio (HR) = 4.17, 95% confidence interval (CI), 3.39–5.13] and AJCC stage IV B (HR = 3.19, 95%CI, 1.79–5.69) were associated with worse prognosis compared with those of AJCC stage III B, while no statistical significance was found in patients with stage IV A (P > 0.05). In terms of the modified staging system, patients with modified stage III C (HR = 2.06, 95%CI, 1.46–2.92), modified stage IV A (HR = 6.91, 95%CI, 4.81–9.94), and modified stage IV B (HR = 21.89, 95%CI, 14.76–32.46) were associated with a poorer prognosis compared with patients with modified stage III B. The prognostic ability (C-index) of the modified staging system (0.789; 95%CI, 0.777–0.801) was better than that of the AJCC 8th edition system (0.762; 95%CI, 0.748–0.776) (0.789 vs. 0.762, P = 0.004). The K-M curves indicated that the modified staging system may be distinguished prognostic differences in patients with different stages. Conclusion Modified staging system may be better than AJCC 8th staging system for predicting prognosis in prostate cancer patients. The AJCC 8th staging system should be further optimized.

In order to solve the problem of difficult coordination of traditional overcurrent relay protection caused by short supply radius and little difference of fault current along urban distribution network, a coordinated relay protection strategy based on economical fault current limiter (FCL) is proposed. The FCL device is configured at the export of the main transformer, by using quick fault identification method, setting different protection current value and relay protection delay time, once the fault occurs, the FCL can quickly limit the fault current first then cooperate with the circuit break and switches on the feeder line to achieved the coordinated relay protection. Combining with faults occurring at different locations along the feeder line, the composition and basic working principle of the FCL are discussed, the theory of fast fault identification method and the setting method of the coordinated relay protection parameters are emphatically discussed. The simulation results show that the proposed current limiting coordinated relay protection strategy can effectively reduce the short-circuit current level and bus voltage drop during the fault handle processing, thus reduce the damage to the distribution system and influence range of the fault, greatly improve the selectivity of the relay protection finally.

The multiport hybrid dc circuit breaker (M-HCB) is a cost-effective choice for fault blocking in meshed HVDC system. Various M-HCB topologies have been proposed in recent years. However, the topology derivation has randomness and uncertainty. Whether the topology can be improved and how to derive new topology from existing topology has less discussion. In this paper, a topology optimization and evaluation method based on graph theory is proposed to deduce more M-HCB topologies from existing topologies. A series of new topologies is quickly derived from the proposed method, and the performance can be evaluated based on the feasible path calculation. Compared with the existing topology, the derived topologies have the advantages of cost and loss in specific application scenarios. Simulation and experiment results are given to verify the topologies. The comparison between the existing topologies proves the superiority of the deduced topologies and the feasibility of the proposed method.

Conjunctival melanoma (CM) is a rare and fatal malignant eye tumor. In this study, we deciphered a novel anti-CM mechanism of a natural tetracyclic compound named as cucurbitacin B (CuB). We found that CuB remarkably inhibited the proliferation of CM cells including CM-AS16, CRMM1, CRMM2 and CM2005.1, without toxicity to normal cells. CuB can also induce CM cells G2/M cell cycle arrest. RNA-seq screening identified KIF20A, a key downstream effector of FOXM1 pathway, was abolished by CuB treatment. Further target identification by activity-based protein profiling chemoproteomic approach revealed that GRP78 is a potential target of CuB. Several lines of evidence demonstrated that CuB interacted with GRP78 and bound with a Kd value of 0.11 μmol/L. Furthermore, ATPase activity evaluation showed that CuB suppressed GRP78 both in human recombinant GRP78 protein and cellular lysates. Knockdown of the GRP78 gene significantly induced the downregulation of FOXM1 and related pathway proteins including KIF20A, underlying an interesting therapeutic perspective. Finally, CuB significantly inhibited tumor progression in NCG mice without causing obvious side effects in vivo. Taken together, our current work proved that GRP78–FOXM1–KIF20A as a promising pathway for CM therapy, and the traditional medicine CuB as a candidate drug to hinder this pathway.

BackgroundSevere fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that was caused by the Dabie bandavirus (DBV), and it has become a global public health threat. Cytokine storm is considered to be an important pathogenesis of critical SFTS. Tripartite motif-containing 3 (TRIM3), as a member of the TRIM protein family, may contribute to the regulation of the immune and inflammatory responses after viral infection. However, whether TRIM3 plays a major role in the pathogenesis of SFTS has not yet been investigated.MethodsTRIM3 mRNA levels were detected in PBMCs between 29 SFTS patients and 29 healthy controls by qRT-PCR. We established the pathogenic IFNAR−/− SFTS mouse model successfully by inoculating subcutaneously with DBV and testing the expression levels of TRIM3 mRNA and protein by qRT-PCR and immunofluorescence in the livers, spleens, lungs, and kidneys. TRIM3OE THP-1 cells and peritoneal macrophages extracted from TRIM3−/− mice were infected with DBV. The effect of TRIM3 on cytokines was detected by qRT-PCR and ELISA. Then we examined Toll-like receptor 3 (TLR3) and protein phosphorylation in the MAPK pathway after DBV infection using Western blot. Flow cytometry was used to verify TLR3 expression on peripheral blood monocytes in SFTS patients. We further explored the interaction between TRIM3 and TLR3 using CO-IP and Western blot.ResultsCompared to healthy controls, TRIM3 mRNA expression in PBMCs is decreased in SFTS patients, especially in severe cases. TRIM3 mRNA and protein were synchronously reduced in the livers, spleens, lungs, and kidney tissues of the IFNAR−/− SFTS mice model. In the DBV-infected cell model, TRIM3 overexpression can inhibit the DBV-induced release of IL-1β, IL-6, and TNF-α, the expression of TLR3, and protein phosphorylation in the MAPK pathway, which plays an anti-inflammatory role, while TRIM3 deficiency exacerbates the pro-inflammatory effects. We further found that TRIM3 can promote TLR3 degradation through K48-linked ubiquitination.ConclusionTRIM3 can inhibit the production of cytokines by regulating the degradation of TLR3 through K48-linked ubiquitination, which can be a therapeutic target for improving the prognosis of SFTS.

ObjectivesInvasive pulmonary aspergillosis (IPA) is common in immuno-compromised people, and a high incidence of IPA has been found in patients with severe fever with thrombocytopenia syndrome (SFTS). Our study aimed to determine the independent risk factors for IPA and the relationship between smoking status and the risk of IPA in SFTS patients.MethodsA retrospective analysis of SFTS patients in the First Affiliated Hospital of Nanjing Medical University from May 2011 to December 2021 was reviewed. The patients were divided into two groups: IPA and non-IPA groups. We compared demographic characteristics, clinical manifestation, laboratory parameters, treatment, and prognosis, and explored the risk factors of IPA using logistic regression and ROC curve. The dose-dependent effect of smoking on the risk of IPA was further estimated, including the age of smoking initiation, daily smoking amount, smoking duration, and pack-years of smoking.ResultsIn total, 189 individuals were included. Compared with the non-IPA group, the IPA group had higher levels of smoking, drinking, cough, dyspnea, aCCI scores, Dabie bandavirus (DBV) RNA load, ferritin, PCT, IL-6, APTT, LDH, BUN, creatinine, and lower levels of FT4 and TSH. The incidences of MODS, admission to ICU, ventilation, and broad-spectrum antibiotic treatment were significantly higher in the IPA group than in the non-IPA group. Multivariable logistic analysis showed that smoking history, cough, creatinine, admission to ICU, broad-spectrum, and corticosteroid therapies were the independent risk factors for IPA in SFTS patients. We further confirmed that the age of smoking initiation

We present an innovative approach to mitigating brightness variations in the unmanned aerial vehicle (UAV)-based 3D reconstruction of tidal flat environments, emphasizing industrial applications. Our work focuses on enhancing the accuracy and efficiency of neural radiance fields (NeRF) for 3D scene synthesis. We introduce a novel luminance correction technique to address challenging illumination conditions, employing a convolutional neural network (CNN) for image enhancement in cases of overexposure and underexposure. Additionally, we propose a hash encoding method to optimize the spatial position encoding efficiency of NeRF. The efficacy of our method is validated using diverse datasets, including a custom tidal flat dataset and the Mip-NeRF 360 dataset, demonstrating superior performance across various lighting scenarios.

The modern urban transportation service network could be split into unrestricted and restricted networks depending on whether travelers face limitations in route selection. Along with the continuous expansion of the city, it is difficult for travelers to find a more reasonable travel solution when confronted with such a complex transportation service network, which combines both unrestricted and restricted networks, especially for the park-and-ride (P&R) travel mode. This paper addresses the issue of route analysis in modern urban transportation service systems to provide travelers with reasonable travel solutions based on multiple types of transportation services. An improved A* algorithm is proposed to address the optimal path analysis for restricted networks to provide reasonable travel solutions for public transportation trips. Furthermore, by establishing the topological relationship between restricted and unrestricted networks, this paper presented an improved A* algorithm based on hybrid networks that solves the optimal path analysis problem for P&R trips, bringing convenience to many urban travelers.