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Background Creatine supplementation aids the Phosphagen system by increasing the amount of free creatine and phosphocreatine available to replenish adenosine triphosphate. The purpose of this study was to investigate the effects of a creatine and electrolyte formulated multi-ingredient performance supplement (MIPS) on strength and power performance compared to a placebo. Maximal strength along with total concentric work, mean rate of force development (mRFD), mean power, peak power, and peak force for both bench press and back squat were determined at pre-test and post-test separated by 6 weeks of supplementation. Methods Twenty-two subjects (6 females, 21 ± 2 yrs., 72.46 ± 11.18 kg, 1.72 ± 0.09 m) performed a one-repetition maximum (1RM) for back squat and bench press. Eighty percent of the subject’s pre-test 1RM was used for a maximal repetition test to assess performance variables. Testing was separated by 6 weeks of supplementation of a MIPS dose per day in a double-blind fashion for comparison. A two-way mixed analysis of covariance (ANCOVA) was applied with an alpha level of 0.05. Results For their back squat 1RM, the MIPS group displayed significant increase of 13.4% (95% CI: 2.77, 23.8%) while placebo displayed a decrease of − 0.2% (95% CI: − 1.46, 2.87%) (p = 0.047, η p 2 = 0.201). The MIPS displayed a significant increase of 5.9% (95% CI: 2.5, 10.1%) and placebo displayed a non-significant increase of 0.7% (95% CI: − 3.49, 3.9%) in bench press maximal strength (p = 0.033,0.217). The MIPS group displayed a significant increase as well in total concentric work (26.5, 95% CI: 6.07, 46.87%, p = 0.008, η p 2 = 0.330) and mean power (17.9, 95% CI: 3.42, 32.46%, p = 0.003, η p 2 = 0.402) for the maximal repetition bench press test at 80% of their 1RM. Conclusions The MIPS was found to be beneficial to recreationally trained individuals compared to a placebo. The greatest benefits are seen in bench press and back squat maximal strength as well as multiple repetition tests to fatigue during the bench press exercise.

Background Creatine supplementation is recommended as an ergogenic aid to improve repeated sprint cycling performance. Furthermore, creatine uptake is increased in the presence of electrolytes. Prior research examining the effect of a creatine-electrolyte (CE) supplement on repeated sprint cycling performance, however, did not show post-supplementation improvement. The purpose of this double blind randomized control study was to investigate the effect of a six-week CE supplementation intervention on overall and repeated peak and mean power output during repeated cycling sprints with recovery periods of 2 min between sprints. Methods Peak and mean power generated by 23 male recreational cyclists (CE group: n = 12; 24.0 ± 4.2 years; placebo (P) group: n = 11; 23.3 ± 3.1 years) were measured on a Velotron ergometer as they completed five 15-s cycling sprints, with 2 min of recovery between sprints, pre- and post-supplementation. Mixed-model ANOVAs were used for statistical analyses. Results A supplement-time interaction showed a 4% increase in overall peak power (pre: 734 ± 75 W; post: 765 ± 71 W; p = 0.040; ηp 2 = 0.187) and a 5% increase in overall mean power (pre: 586 ± 72 W; post: 615 ± 74 W; p = 0.019; ηp 2 = 0.234) from pre- to post-supplementation for the CE group. For the P group, no differences were observed in overall peak (pre: 768 ± 95 W; post: 772 ± 108 W; p = 0.735) and overall mean power (pre: 638 ± 77 W; post: 643 ± 92 W; p = 0.435) from pre- to post-testing. For repeated sprint analysis, peak (pre: 737 ± 88 W; post: 767 ± 92 W; p = 0.002; ηp 2 = 0.380) and mean (pre: 650 ± 92 W; post: 694 ± 87 W; p

Cross-country running is becoming an increasingly popular sport, with a significant participation noted at the high school level. The aim of this study was to compare gender and bilateral hip extension range of motion and hip and knee extension strength of high school cross-country runners. 31 participants volunteered from a local high school cross-country team (16 males and 15 females). The modified Thomas test was utilized to measure hip extension range of motion bilaterally using a digital inclinometer. In order to measure hip and knee isometric strengths, an isokinetic dynamometer was employed. A mixed model approach revealed a statistically significant difference in peak hip extension strength between genders but not the side. Male athletes demonstrated a 29.2 Nm/kg (P

Uncertainties surrounding the evolutionary origin of the epipelagic fish family Scombridae (tunas and mackerels) are symptomatic of the difficulties in resolving suprafamilial relationships within Percomorpha, a hyperdiverse teleost radiation that contains approximately 17,000 species placed in 13 ill-defined orders and 269 families. Here we find that scombrids share a common ancestry with 14 families based on (i) bioinformatic analyses using partial mitochondrial and nuclear gene sequences from all percomorphs deposited in GenBank (10,733 sequences) and (ii) subsequent mitogenomic analysis based on 57 species from those targeted 15 families and 67 outgroup taxa. Morphological heterogeneity among these 15 families is so extraordinary that they have been placed in six different perciform suborders. However, members of the 15 families are either coastal or oceanic pelagic in their ecology with diverse modes of life, suggesting that they represent a previously undetected adaptive radiation in the pelagic realm. Time-calibrated phylogenies imply that scombrids originated from a deep-ocean ancestor and began to radiate after the end-Cretaceous when large predatory epipelagic fishes were selective victims of the Cretaceous-Paleogene mass extinction. We name this clade of open-ocean fishes containing Scombridae "Pelagia" in reference to the common habitat preference that links the 15 families.

APOE ɛ4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE ɛ4+ (10 352 cases and 9207 controls) and APOE ɛ4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE ɛ4 status. Suggestive associations (P

Abstract For the blasting scenario, our research develops an emulsion explosive grasping and filling system suitable for tunnel robots. Firstly, we designed a system, YOLO-SimAM-GRCNN, which consists of an inference module and a control module. The inference module primarily consists of a blast hole position detection network based on YOLOv8 and an explosive grasping network based on SimAM-GRCNN. The control module plans and executes the robot’s motion control based on the output of the inference module to achieve symmetric grasping and filling operations. Meanwhile, The SimAM-GRCNN grasping network model is utilized to carry out comparative evaluated on the Cornell and Jacquard dataset, achieving a grasping detection accuracy of 98.8% and 95.2%, respectively. In addition, on a self-built emulsion explosive dataset, the grasping detection accuracy reaches 96.4%. The SimAM-GRCNN grasping network model outperforms the original GRCNN by an average of 1.7% in accuracy, achieving a balance between blast holes detection, grasping accuracy and filling speed. Finally, experiments are conducted on the Universal Robots 3 manipulator arm, using distributed deployment and manipulator arm motion control mode to achieve an end-to-end grasping and filling process. On the Jetson Xavier NX development board, the average time consumption is 119.67 s, with average success rates of 87.1% for grasping and 79.2% for filling emulsion explosives.

Abstract Neoadjuvant PD-1 inhibitor is promising in cutaneous melanoma but remains unknown in acral melanoma (AM). This phase Ib trial study (Clinicaltrials.gov NCT04197882) assessed the efficacy and safety of the combination of neoadjuvant oncolytic virus orienX010 (ori) and anti-PD-1 toripalimab (tori) for resectable AM. Thirty patients of stage III/IV received neoadjuvant therapy of ori and tori for 12 weeks before surgery, followed by adjuvant treatment with tori for 1 year. Primary endpoints were radiographic and pathological response rates, with secondary endpoints of 1- and 2-year recurrence-free survival (RFS) rates, event-free survival (EFS) rates, and safety. Twenty-seven completed surgery and tori adjuvant treatment and median follow-up was 35.7 months. Radiographic and pathological response rates were 36.7% and 77.8%, with complete response rates of 3.3% and 14.8%, 1- and 2-year RFS rates of 85.2% and 81.5%, and 1- and 2-year EFS rates of 83% and 73%, respectively. Adverse events occurred in all patients, mainly grade 1–2. There was no correlation between PET/CT evaluation and pathological response or progression-free survival/overall survival. Patients with pathological response showed tumor beds with high tertiary lymphoid structures (TLSs) and tumor-infiltrating lymphocytes (TILs). Cytokines and chemokines analysis showed the combination therapy significantly increases the secretion of proinflammatory cytokines and chemokines in both responders and non-responders. Therefore, neoadjuvant ori and tori demonstrated promising antitumor activity with high response rates and high 2-year RFS/EFS for AM with acceptable tolerability.

Abstract Aim The present work set out to classify cell subpopulations related to liver metastasis from gastric cancer (GC) and the mechanisms of their interactions with other immune cell subpopulations. Background GC is characterized by a high degree of heterogeneity and liver metastasis. Exploring the mechanism of liver metastasis of GC from the perspective of heterogeneity of the tumor microenvironment (TME) might help improve the efficacy of GC treatment. Objective Based on the cellular subpopulation characteristics of GC with liver metastasis, the regulatory mechanisms contributing to GC progression were analyzed, with special focuses on the roles of signaling pathways, transcription factors (TFs) and ligand–receptor pairs. Methods The GSE163558 dataset was downloaded from the Gene Expression Omnibus (GEO) database to collect single-cell transcriptomic data of GC patients and their metastasis groups for cell clustering and relevant analyses. Differentially expressed genes (DEGs) in the GC and GC liver metastasis groups were screened and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. SCENIC analysis was used to mine TFs that affected cellular subpopulations during liver metastasis from GC. The relative expression levels of TFs in GC were determined using qRT-PCR. Transwell and wound healing assays were utilized to verify the regulation of the TFs on the migration and invasion of GC cells. Interaction network between the cellular subpopulations was developed applying CellChat. Results Single-cell clustering was performed to group six major cell subpopulations, namely, Myeloid cells, B cells, Mast cells, Epithelial cells, Fibroblasts, and TNK cells, among which the number of TNK cells was significantly increased in the GC liver metastasis group. Differentially enriched pathways of TNK cells between GC and GC liver metastasis groups mainly included IL-17 and Pi3k–Akt signaling pathways. TNK cell subsets could be further categorized into CD8 T cells, Exhausted T cells, NK cells, NKT cells, and Treg cells, with the GC liver metastasis group showing significantly more CD8 T cells and NKT cells. FOS and JUNB were the TFs of TNK cell marker genes that contributed to liver metastasis from GC and the invasion and migration of GC cell lines. Significant differences in immune cell communication ligand–receptor pairs existed between the GC and GC liver metastasis groups. Conclusion This study revealed the critical role of TNK cell subsets in GC with liver metastasis applying single-cell transcriptomics analysis. The findings provided an important theoretical basis for developing novel therapies to inhibit liver metastasis from GC.

Abstract Pyroptosis is a lytic and inflammatory form of gasdermin protein-mediated programmed cell death that is typically initiated by inflammasomes. The inflammasome response is an effective mechanism for eradicating germs and cancer cells in the event of cellular injury. The gasdermin family is responsible for initiating pyroptosis, a process in which holes are made in the cell membrane to allow inflammatory chemicals to escape. Mounting evidence indicates that pyroptosis is critical for controlling the development of cancer. In this review, we provide a general overview of pyroptosis, examine the relationship between the primary elements of pyroptosis and tumors, and stress the necessity of pyroptosis-targeted therapy in tumors. Furthermore, we explore its dual nature as a double-edged sword capable of both inhibiting and facilitating the growth of cancer, depending on the specific conditions. Ultimately, pyroptosis is a phenomenon that has both positive and negative effects on tumors. Using this dual impact in a reasonable manner may facilitate investigation into the initiation and progression of tumors and offer insights for the development of novel treatments centered on pyroptosis.

Abstract The long-term operation performance of HVDC transmission systems is significantly influenced by the reliability of thyristors. However, the current reliability research of thyristors is mainly based on the leakage current and there is no comprehensive degradation characteristics of thyristors. In this article, the degradation characteristics of thyristors under voltage and temperature accelerated ageing tests are obtained, including the reverse recovery characteristic, on-state characteristic, blocking characteristic and gate characteristic. The reverse recovery characteristic obviously degrades under the voltage accelerated ageing tests. The reverse recovery charge and reverse recovery time decrease by over 10% after the tests. Seven thyristors operating for a certain number of years from two HVDC stations are tested, and the results verify the thyristor degradation characteristics obtained from the ageing tests. Moreover, the mechanisms of the leakage current and reverse recovery characteristic are analyzed in detail.

Abstract Severe psoriasis has a long course and poor outcome, and it has long been a problem for patients. Understanding the independent risk factors that contribute to patients with severe psoriasis is critical for the development of effective treatment strategies. This large, multicenter study recruited 2,109 plaque psoriasis patients from 12 hospitals across China (October 31, 2019 – May 31, 2022). The logistic regression model underwent internal validation and external validation using two independent cohorts over future time periods (June 1, 2022 – January 31, 2023). The discriminative power of our model was substantiated by a C-index of 0.863 (95% CI: 0.848–0.879) in internal validation, further affirmed through 1,000 bootstrap validation (C-index: 0.860, 95% CI: 0.836–0.885) and external validation cohorts, where the C-index reached up to 0.910 (95% CI: 0.868–0.953) and 0.951 (95% CI: 0.924–0.977) in 2 external validation cohorts. To enhance accessibility for clinicians, the model has been made available as a dynamic nomogram and QR code. Our study identified 10 risk factors (the “DELPHI” consensus dichotomy, the DLQI index, the extent of skin involvement as measured by body surface area, the age of the patient at the time of clinical visit, sex, body weight in kilograms, career, the presence of scalp involvement, facial involvement, and arthropathy) for the overall severity of psoriasis (PASI ≥ 10). “Nomogram-10” provides clinicians with a practical tool to develop personalized intervention strategies based on an individual’s risk profile. Trial registration: Chinese Clinical Trial Registry: ChiCTR1900024852.

Abstract Clinical studies and meta-analyses have suggested a link between thyroid dysfunction and lens opacification. The objective of this study is to investigate the causal relationship between hyperthyroidism and the development of cataracts using the Mendelian randomization approach, with the aim of filling the gap in knowledge about the systemic effects of hyperthyroidism on ocular health. Leveraging genetic variants as instrumental variables, the analysis used extensive datasets from the UK Biobank and the FinnGen Database and employed three common approaches for causal inference (the Inverse Variance Weighted method, a regression based method the Weighted Median estimator, and MR-Egger regression) and accompanying sensitivity analyses to ensure robustness. The results demonstrate that there is a strong likely causal relationship, with hyperthyroidism increasing the risk of developing senile cataracts (OR = 361.09, 95%CI 5.024 to 2.60 × 104, P = 0.007). A sensitivity analysis provided no evidence of horizontal pleiotropy and no significant outliers, suggesting the results are robust. In conclusion, our study established a significant causal relationship between hyperthyroidism and increased risk of cataract development, underscoring the importance of considering the systemic effects of hyperthyroidism in clinical and public health interventions and policies. Future research should focus on elucidating the molecular mechanisms underlying this association, exploring the potential benefits of early intervention in hyperthyroidism to prevent cataract development, and investigating whether these findings translate across different ethnic populations. Additionally, further GWAS studies aimed at identifying genetic variants associated with both hyperthyroidism and cataracts are warranted to confirm and expand upon our results.

Abstract Background The discovery of viruses in small mammalian populations, particularly rodents, has expanded the family Paramyxoviridae. The overlap in habitats between rodents and humans increases the risk of zoonotic events, underscoring the importance of active surveillance. Rodent species, such as Apodemus agrarius, are natural hosts for Paramyxoviridae in the Republic of Korea (ROK). However, it is unknown whether Paramyxoviridae is present in Micromys minutus, another common rodent. Method Here, we screened M. minutus collected from the Gangwon Province in the ROK for paramyxoviruses using nested polymerase chain reaction and confirm positive samples by next-generation metagenomic sequencing. Complete paramyxovirus genomes were further characterized by phylogenetic analysis, amino acid similarity, secondary structure, and cophylogeny. Result Overall, 57 of 145 (39.3%) M. minutus kidney samples tested positive for paramyxoviruses. Among them, four whole genome sequences were identified and clustered within the genus Jeilongvirus. One sequence was determined as Samak Micromys paramyxovirus 1 (SMPV-1; 19,911 nucleotides long) and three sequences as Samak Micromys paramyxovirus 2 (SMPV-2; 18,199 nucleotides long). SMPV-1 has a smaller hydrophobic gene and a longer glycoprotein gene than SMPV-2. Cophylogenetic analysis suggests that SMPV-1 evolved through co-divergence, whereas SMPV-2 was inferred to have undergone transfer events. Conclusion These findings highlight the prevalence of paramyxoviruses in the wild and the potential of M. minutus as a natural viral reservoir. The discovery of SMPV-1 and SMPV − 2 also reveals the genetic diversity and evolutionary history of the genus Jeilongvirus in the Paramyxoviridae.

Abstract Prostate cancer (PCa), with high heterogeneity and poor prognosis, is one of the most common malignant tumors in men. Circular RNAs (circRNAs) have been identified in tumor progression and resistance to medication in numerous studies. However, the role of circ_0001047 in PCa is unclear. In this research, we found that circ_0001047 had low expression in PCa cells and tissues and was negatively correlated with testosterone secretion in vivo. Overexpression of circ_0001047 inhibited the proliferation, migration, invasion, and anti-apoptotic abilities of human PCa cells in vitro. Mechanistically, circ_0001047 promoted the expression of FKBP5 through sponge adsorption of miR-122-5p and then inhibited the proliferation, anti-apoptotic migration, and invasion abilities of PCa cells. In addition, overexpression of circ_0001047 enhanced the sensitivity of PCa cells to abiraterone by inhibiting AKT phosphorylation activation through upregulation of FKBP5/PHLPP1. This study revealed a novel mechanism by which circ_0001047 regulates PCa progression and treatment sensitivity via the miR-122-5p/FKBP5/PHLPP1/AKT axis. These findings deepen our comprehension of the molecular mechanisms in latent PCa progression and treatment resistance. Graphical Abstract

Abstract Background The post COVID-19 health condition of Chinese residents infected with Omicron is not clear after the change of epidemic prevention policies. This study aimed to clarify the epidemiology and associated factors about health status of rehabilitation patients. Methods A quick questionnaire study based on C19-YRSm was conducted in mainland China through internet from May 1, 2023, to May 7, 2023. Chinese native speakers infected with Omicron variant agreed to participate were included. Persisting symptom and living habits were simultaneously inquired. Logistic regression analysis was used to identify the associated factors. Results In this study 753 individuals were included. Of whom 57.90% were males, 89.38% did not seek medical service, 99.47% recovered within less than 120 days. Breathlessness (47.68%), cognitive impairment (44.89%), Anxiety/mood changes (33.20%), pain/discomfort (32.94%), fatigue or tiredness not improved by rest (32.27%) and post-exertional malaise (30.01%) were the top reported key symptoms. Less than 10% respondents reported functional limitations. The prevalence of fever was reported greater than that of other symptoms, with dry eyes at 14.87%, appetite change at 14.34%, and hair loss at 12.22%. Middle age (OR: 2.353, 95%CI: 1.171 ~ 4.729), underlying diseases (OR: 2.293, 95%CI: 1.216 ~ 4.324), severe key symptom (OR: 6.168, 95%CI: 1.376 ~ 27.642) and at least one other symptom (OR: 1.847, 95%CI: 1.225 ~ 2.718)during the recovery were the risk factors of poor overall health after infection (current overall health score

Abstract Objective This study aims to evaluate the long-term outcomes of compensatory hyperhidrosis (CH) after thoracoscopic sympathectomy and explore the risk factors affecting postoperative CH in primary palmar hyperhidrosis(PPH) patients. Method A retrospective analysis was conducted on patients who underwent thoracoscopic sympathectomy in the thoracic surgery department of our hospital from January 2015 to May 2022. Long-term follow-up surveys was conducted to collect data on post-operative satisfaction, PPH recurrence, and CH occurrence. Postoperative CH outcomes were assessed using the HDSS and satisfaction scores scale. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for postoperative CH. Result A total of 152 patients was included in the final study, with 113 cases in the CH group and 39 cases in the nCH group. The incidence of postoperative CH was 74.3% (113/152), within which 33.6% (38/113) were severe CH. The median follow-up time was 3.1 years(2.5-5.5y) and the median interval of CH onset after surgery was 30 days (14-90d). Univariate analysis showed that body mass index(BMI), surgical time, and transected nerve level are correlated with CH, with statistically significant differences. Multivariate logistic regression analysis indicated a higher BMI (OR = 0.864, 95% CI 0.755–0.989, P

Abstract Background Hydrogen sulfide (H2S), the third gasotransmitter discovered, regulates a variety of physiological functions. Whether H2S alleviates skeletal muscle ageing by regulating autophagy has not been reported. Methods Mice were administered 150 mg/kg/day of D‐galactose (D‐gal), and C2C12 myotubes were cultured in 20 g/L D‐gal to induce ageing. Sodium hydrosulfide (NaHS) was employed as an exogenous donor in the treatment group. The intracellular concentration of H2S was quantified by the 7‐azido‐4‐methylcoumarin fluorescence probe. The proteins involved in the ubiquitin‐mediated degradation of AMPKα1 were detected by liquid chromatography tandem mass spectrometry (LC–MS/MS) and co‐immunoprecipitation (Co‐IP). S‐sulfhydration of USP5 was tested by a biotin‐switch assay. Associated proteins were analysed by western blot. Results NaHS was found to effectively restore the H2S content in both ageing gastrocnemius (+91.89%, P

Abstract The Eastern Zhou period of China, characterised by complex interactions among vassal states, witnessed significant advancements in bronze production technology. However, the investigation of interactions based on technological comparison among dominant and dependent states remains limited. Focusing on two newly excavated foundry sites, Baidian in Houma, Shanxi, and Xincun in Hebi, Henan, this study provides crucial insights into the bronze production technologies and material sources used by Jin, a major vassal state in Central China, and Wei, a dependent state of Jin, during the Eastern Zhou period. Elemental analysis and microstructural examinations of slags, fragments of crucible wall and furnace wall, show the diversity of bronze production techniques between these two sites: in the Baidian site, bronzes were predominantly produced by co-melting of metallic copper and tin, and remelting of recycled bronzes, whereas in the Xincun site, bronze were probably made by co-melting of copper and tin ore. Furthermore, lead isotope analysis results suggest that the lead materials used for the bronze production at both the sites were likely from the Xiaoqinling region. Integrated with the historical background of complex interactions among vassal states, these findings not only shed light on the technological advancements and resource networks of the Jin and Wei states but also explain the relationships between technology, resources and social dynamics from various perspective. Hopefully this research would promote archeometallurgical study among regions and be applied to other Bronze Age cultures in the world.

Abstract Treatment options for patients with relapsed extensive-stage small cell lung cancer (ES-SCLC) remain scarce. This study aims to evaluate the efficacy and safety of combining anlotinib and sintilimab plus chemotherapy as a second line or later therapy for ES-SCLC patients. This is a phase II clinical trial (ChiCTR2100049390) conducting at Shandong Cancer Hospital. Patients with ES-SCLC and received at least one prior systemic treatment were enrolled. The trial design involved a combination therapy (sintilimab, anlotinib, and nab-paclitaxel) administered over six 21-day cycles, followed by maintenance sintilimab therapy. The primary endpoint was objective response rate (ORR). Circulating tumor DNA sequencing was employed for exploratory analysis. From July 2021 to April 2023, 25 eligible patients were enrolled. The confirmed ORR was 60% (95% CI: 38.7–78.9%) and the DCR was 76% (95% CI: 54.9–90.6%). The mPFS was 6.0 months (95% CI: 5.4–9.7), and the 6-month PFS rate was 49.2%. The mOS was 13.4 months (95% CI: 11.8-NR), with a 12-month survival rate of 62.2%. Treatment-related adverse events (TRAEs) of any grade occurred in 80% of patients, with the most common being fatigue (40%) and nausea (32%). TRAEs of Grade 3 or higher were reported in 12% of patients. ctDNA analysis indicated that low on-treatment blood tumor mutation burden was associated with longer PFS and OS and a potential role of KMT2D mutation in treatment resistance. This combination therapy shows promising efficacy and a manageable safety profile as a second-line or later treatment for ES-SCLC, with genomic insights providing potential biomarkers for treatment response.

The mechanical response characteristics of rock under low-frequency perturbation loads and high-stress conditions are important factors affecting the stability of interlayer rock in the goaf during upward mining. Taking the coal-bearing sedimentary rock sandstone as the research object, the dynamic uniaxial compression tests were conducted on high-stress sandstone (80%UCS) under low-frequency perturbation loads (5 Hz) using a self-developed dynamic-static coupled electro-hydraulic servo testing machine. The progressive damage behavior and nonlinear mechanical dynamic response characteristics of high-stress rock under low-frequency perturbations were revealed. The results are as follows: ① During the process of small amplitude low-frequency disturbance load, high-stress sandstone does not experience dynamic failure, the threshold value of low-frequency disturbance load amplitude to induce sandstone damage is 15%UCS. Under the action of low-frequency disturbance load above the threshold value, the number of disturbance load cycles before the failure of high-stress sandstone decreases exponentially with the increase of amplitude. ② The progressive initiation and accumulation of randomly distributed microcracks within the sandstone, as well as their gradual extension, significantly affect the nonlinear evolution characteristics of dynamic secant modulus, strain peak, plastic deformation, dissipated energy density, and b-value. ③ During the low-frequency perturbation process, the b-value and dissipated energy density exhibit a three-stage evolution characteristic consistent with the strain. The exponential strain evolution curve has a distinct inflection point before the failure of the sandstone, which can serve as a precursor information of dynamic failure under low-frequency perturbations and be used for corresponding dynamic disaster warnings. ④ During the low-frequency perturbation load process beyond the threshold, the dynamic secant modulus evolution curve approximates an exponential decay. The parameters in the nonlinear fitting relationship can be used to quantify the degradation rate of the elastic modulus. And the degradation rate of secant modulus of sandstone changes nonlinearly with the increase of amplitude. ⑤ The magnitude of the RA value in the initial stage of disturbance load can be used to predict the dynamic failure of sandstone in advance. Correspondingly, the sudden increase of RA during the low-frequency disturbance load process can serve as a precursor warning of dynamic instability of high stress sandstone. During the process of small-amplitude disturbance load below the threshold value, the microcracks mainly undergo tensile or mixed fracture, with shear fracture accounting for only 12.15%. During the low-frequency disturbance load processes with amplitudes of 15%UCS, 20%UCS, and 25%UCS, the shear fracture accounts for 37.17%, 52.75%, and 53.62% respectively. The proportion of shear fractures exhibits a logarithmic increase with the increase of amplitude.

Abstract Severity of deceased donor kidney fibrosis impacts graft survival in deceased-donor kidney transplantation. Our aim was to identify potential miRNA biomarkers in urinary exosomes that mirror interstitial fibrosis and tubular atrophy (IFTA) severity. Among 109 urine samples from deceased donors, 34 displayed no IFTA in the zero-day biopsy (No IFTA group), while the remaining 75 deceased donor kidneys exhibited an IFTA score ≥ 1 (IFTA group). After analyzing previous reports and electronic databases, six miRNAs (miR-19, miR-21, miR-29c, miR-150, miR-200b, and miR-205) were selected as potential IFTA biomarker candidates. MiR-21, miR-29c, miR-150, and miR-205 levels were significantly higher, while miR-19 expression was significantly lower in the IFTA group. MiR-21 (AUC = 0.762; P

Data-driven fault diagnosis techniques are significant for the stable operation of nuclear power plants (NPPs). However, in practical applications, the fault diagnosis of NPPs usually faces imbalance data problems with small fault samples and much redundant data which results in low model training efficiency and poor generalization performance. Thus, this paper proposes a convolutional variational autoencoding gradient-penalty Wasserstein generative adversarial network with random forest (CVGR) to reduce the impact of imbalanced samples on fault diagnosis. Firstly, a feature selection method based on the random forest is used to identify the most relevant measurements and reduce the impact of redundant data on fault diagnosis. Then, variational autoencoding is introduced into gradient-penalty Wasserstein generative adversarial to effectively extract original sample features and generate high-quality samples with high rationality and diversity. In addition, the convolutional neural network is used to extract the features of mixed samples to realize intelligent fault diagnosis. Finally, several experiments based on the Fuqing Unit 2 full-scope simulator under different operating conditions are used to validate the performance of the CVGR in data enhancement and intelligent fault diagnosis. The results show that the proposed method can effectively mitigate the imbalance data problem, which gives insights into intelligent fault diagnosis of NPPs.

Adenoid cystic carcinoma (ACC) is a rare malignancy predominantly found in the salivary, lacrimal, upper gastrointestinal, and respiratory mucosal glands; adenoid cystic carcinoma of the external auditory canal (EAC) is particularly rare. Characterized by a proclivity for recurrence and metastasis, advanced adenoid cystic carcinoma often proves refractory to conventional chemotherapy. Novel therapeutic approaches, notably targeted therapies, are imperative to enhance treatment response rates in advanced adenoid cystic carcinoma patients. Herein, we present a case of primary adenoid cystic carcinoma affecting the right external auditory canal in a 56-year-old male presenting with symptoms of pruritus, swelling, pain, and hearing loss in the affected ear. Despite multiple attempts with diverse chemotherapy regimens yielding no success, the patient developed advanced lung metastases, prompting the utilization of anlotinib-targeted therapy. Subsequent administration of anlotinib led to a partial remission (PR), resulting in approximately 8 months of progression-free survival (PFS) in this individual.

【Objective】Guizhou Province is an area for annual breeding of Spodoptera frugiperda. The use of molecular markers were used to identify the population biotypes of S. frugiperda in Guiyang, Guizhou, and its adaptability to Zea mays, Sorghum bicolor and Oryza sativa were studied, with a view to clarifying the biotype of S. frugiperda invading Guiyang and understanding the characteristics of its biotypes.【Method】A total of 32 S. frugiperda samples from three counties or cities in Guiyang, Guizhou were amplified, sequenced and analyzed for comparison by using CO Ⅰ and Tpi molecular marker methods, to determine the biotype of the population invading Guiyang, Guizhou. Additionally, the developmental duration, adult emergence rate and survival time of S. frugiperda larvae of various instars after feeding on three host plants (Zea mays, S. bicolor and O. sativa) were recorded to evaluate the adaptability of S. frugiperda to these three host plants.【Result】The results showed that among the 32 S. frugiperda samples, 93.75% belonged to the rice biotype while 6.25% belonged to the corn biotype based on the mitochondrial CO Ⅰ gene analysis. The sequence characteristics were highly consistent with the corresponding biotypes of S. frugiperda population. Meanwhile, the analysis of nuclear genome Tpi gene revealed that all samples showed the haplotype characteristics of the corn strain. The adaptability study indicated that the invasive S. frugiperda in Guiyang had the shortest larval period (13.22 d), longest adult survival time (16.42 d) and highest emergence rate (95.14 %) on Z. mays, followed by S. bicolor; while it had the longest larval period (16.59 d), shortest adult survival time (8.56 d) and lowest emergence rate (75.15 %) on O. sativa.【Conclusion】The biotypes of S. frugiperda invaded Guiyang, Guizhou Province were 93.75% rice type, 6.25% maize type using CO Ⅰ molecular marker, and 100% maize type using Tpi molecu lar marker. The life span of female S. frugiperda feeding on maize was significantly higher than those feeding on rice and S. bicolor. The results provide a basis for the prevention and control of S. frugiperda on S. bicolor.

The accurate determination of coal temperature in the hidden spaces such as goaf has always been a worldwide problem that needs to be solved urgently. The study of acoustic temperature measurement technology is of great practical significance for a fast and accurate detection of loose coal temperature, and the scientific and accurate construction of the mapping relationship between sound velocity and coal temperature is the key to acoustic coal temperature measurement. In this paper, considering the influence of the characteristic parameters of spontaneous combustion process of loose coal on sound wave propagation, a mapping model of sound velocity and coal temperature in the quasi-porous media of loose coal was established. An acoustic temperature measurement experimental system for loose coal was designed and built. By conducting the acoustic temperature measurement tests for the loose coal with various particle sizes (0.6～1.5, 1～3, 3～5 cm), the effect of gas composition and concentration on sound propagation during the low-temperature oxidation stage (30～50 ℃) of coal samples with different particle sizes was studied, and the equivalent path conversion factor λ was determined. Based on the relationship between the measured sound velocity and the equivalent path conversion factor, the medium correction coefficient φ of the gas component was proposed and determined, and the feasibility of the sound-temperature mapping relationship model was verified. The results show that the acoustic wave propagation path of loose coal is affected by the characteristic parameters of coal particle size, temperature and the change of gas component medium, etc. A mapping model of sound velocity and coal temperature was established. At normal temperature, the propagation path of sound waves in the quasi-porous medium of loose coal is mainly affected by the pores between the coal particles. The equivalent path conversion factor λ of sound waves is 1.426 1, 1.371 1 and 1.315 2, respectively, when the coal particle size is 0.6～1.5, 1～3, 3～5 cm, which is negatively correlated with the particle size. The influence of coal temperature on acoustic wave propagation is manifested by the change of gas component medium in the process of spontaneous combustion of coal, which verifies the feasibility of the mapping relationship between sound velocity and coal temperature. The error rate between the inversion model and the experimental coal temperature is 0～6.46%, and the average coal temperature error is 2.52 ℃, which can reflect the coal body temperature well.

Abstract In the burgeoning field of quantum topological photonics, waveguide systems play a crucial role. This perspective delves into the intricate interplay between photonic waveguides and topological phenomena, underscoring the theoretical underpinnings of topological insulators and their photonic manifestations. We highlight key milestones and breakthroughs in topological photonics using waveguide systems, alongside an in-depth analysis of their fabrication techniques and tunability. The discussion includes the technological advancements and challenges, limitations of current methods, and potential strategies for improvement. This perspective also examines the quantum states of light in topological waveguides, where the confluence of topology and quantum optics promises robust avenues for quantum communication and computing. Concluding with a forward-looking view, we aim to inspire new research and innovation in quantum topological photonics, highlighting its potential for the next generation of photonic technologies.

Abstract Background Cuproptosis is a unique copper-dependent form of cell death that is highly correlated with the metabolic state of cells. Triptolide exerts pharmacological activity by altering the regulation of metal ions. Cuproptosis is poorly understood in cancer, so in this study, we explored whether triptolide could induce cuproptosis in cervical cancer cells. Methods The human cervical cancer cell lines HeLa and SiHa, which primarily rely on oxidative phosphorylation, were treated with triptolide. Cell viability, proliferation and migration, copper levels and cuproptosis-related protein levels were evaluated in these cell lines. The copper ion chelator tetrathiomolybdate (TTM) was administered to determine whether it could reverse the cuproptosis induced by triptolide. In addition, a nude mouse cervical cancer xenograft model was established to determine the effects of triptolide on cuproptosis in isolated tumor tissues. Results The copper concentration increased with triptolide treatment. The levels of cuproptosis -related proteins, such as FDX1, LIAS, and DLAT, in the HeLa and SiHa cell lines decreased with triptolide treatment. XIAP, the target of triptolide, played a role in cuproptosis by regulating COMMD1. The level of copper exporters (ATP7A/B) decreased, but the level of the copper importer (CTR1) did not change with triptolide treatment. Furthermore, triptolide inhibited cervical cancer growth and induced cuproptosis in vivo. Conclusions In summary, we report a new antitumor mechanism by which triptolide disrupted intracellular copper homeostasis and induced cuproptosis in cervical cancer by regulating the XIAP/COMMD1/ATP7A/B axis.

Abstract Malignant melanoma represents a particularly aggressive type of skin cancer, originating from the pathological transformation of melanocytes. While conventional interventions such as surgical resection, chemotherapy, and radiation therapy are available, their non-specificity and collateral damage to normal cells has shifted the focus towards immunotherapy as a notable approach. Extracellular vesicles (EVs) are naturally occurring transporters, and are capable of delivering tumor-specific antigens and directly engaging in the immune response. Multiple types of EVs have emerged as promising platforms for melanoma vaccination. The effectiveness of EV-based melanoma vaccines manifests their ability to potentiate the immune response, particularly by activating dendritic cells (DCs) and CD8+ T lymphocytes, through engineering a synergy of antigen presentation and targeted delivery. Here, this review mainly focuses on the construction strategies for EV vaccines from various sources, their effects, and immunological mechanisms in treating melanoma, as well as the shortcomings and future perspectives in this field. These findings will provide novel insights into the innovative exploitation of EV-based vaccines for melanoma immune therapy.

Abstract Biological ion channels usually conduct the high-flux transport of 107 ~ 108 ions·s− 1; however, the underlying mechanism is still lacking. Here, by applying the KcsA potassium channel as a typical example, and performing multitimescale molecular dynamics simulations, we demonstrate that there is coherence of the K+ ions confined in biological channels, which determines transport. The coherent oscillation state of confined K+ ions with a nanosecond-level lifetime in the channel dominates each transport event, serving as the physical basis for the high flux of ~108 ions∙s− 1. The coherent transfer of confined K+ ions only takes several picoseconds and has no perturbation effect on the ion coherence, acting as the directional key of transport. Such ion coherence is allowed by quantum mechanics. An increase in the coherence can significantly enhance the ion conductance. These findings provide a potential explanation from the perspective of coherence for the high-flux ion transport with ultralow energy consumption of biological channels.

Abstract Acquiring multi-dimensional optical information, such as intensity, spectrum, polarization, and phase, can significantly enhance the performance of photodetectors. Incorporating these dimensions allows for improved image contrast, enhanced recognition capabilities, reduced interference, and better adaptation to complex environments. However, the challenge lies in obtaining these dimensions on a single photodetector. Here we propose a misaligned unipolar barrier photodetector based on van der Waals heterojunction to address this issue. This structure enables spectral detection by switching between two absorbing layers with different cut-off wavelengths for dual-band detection. For polarization detection, anisotropic semiconductors like black phosphorus and black arsenic phosphorus inherently possess polarization-detection capabilities without additional complex elements. By manipulating the crystal direction of these materials during heterojunction fabrication, the device becomes sensitive to incident light at different polarization angles. This research showcases the potential of the misaligned unipolar barrier photodetector in capturing multi-dimensional optical information, paving the way for next-generation photodetectors.

Abstract On a global note, oral health plays a critical role in improving the overall human health. In this vein, dental-related issues with dentin exposure often facilitate the risk of developing various oral-related diseases in gums and teeth. Several oral-based ailments include gums-associated (gingivitis or periodontitis), tooth-based (dental caries, root infection, enamel erosion, and edentulous or total tooth loss), as well as miscellaneous diseases in the buccal or oral cavity (bad breath, mouth sores, and oral cancer). Although established conventional treatment modalities have been available to improve oral health, these therapeutic options suffer from several limitations, such as fail to eradicate bacterial biofilms, deprived regeneration of dental pulp cells, and poor remineralization of teeth, resulting in dental emergencies. To this end, the advent of nanotechnology has resulted in the development of various innovative nanoarchitectured composites from diverse sources. This review presents a comprehensive overview of different nanoarchitectured composites for improving overall oral health. Initially, we emphasize various oral-related diseases, providing detailed pathological circumstances and their effects on human health along with deficiencies of the conventional therapeutic modalities. Further, the importance of various nanostructured components is emphasized, highlighting their predominant actions in solving crucial dental issues, such as anti-bacterial, remineralization, and tissue regeneration abilities. In addition to an emphasis on the synthesis of different nanostructures, various nano-therapeutic solutions from diverse sources are discussed, including natural (plant, animal, and marine)-based components and other synthetic (organic- and inorganic-) architectures, as well as their composites for improving oral health. Finally, we summarize the article with an interesting outlook on overcoming the challenges of translating these innovative platforms to clinics. Graphical abstract