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Abstract This study investigates the interplay between distal adverse childhood experiences (ACEs) and proximal psychological risk factors in predicting suicidal ideation among men who have sex with men (MSM) using network analysis. A total of 1138 MSM completed self-reported questionnaires on demographics, ACEs, depression, anxiety, interpersonal needs, and suicidal ideation. We employed Gaussian graphical models to perform a network analysis that mapped the relationships between ACEs and proximal psychological variables and identified bridge nodes. Additionally, suicidal ideation was incorporated to reevaluate the network and explore the association between the identified bridge nodes and suicidal ideation. The results show that approximately 88.3% of participants reported experiencing ACEs, with an average occurrence of 3.4 types of ACEs. Suicidal ideation was reported by 31.3% of participants. Key bridging nodes in the psychosocial network included perceived burdensomeness, thwarted belongingness, feeling tired/having little energy, and excessive worrying. Perceived burdensomeness exhibited the strongest correlation with suicidal ideation, followed by thwarted belongingness. Moreover, neglect is strongly associated with suicidal ideation. Our findings suggest that ACEs are associated with suicidal ideation and may be linked to specific proximal psychological factors that correlate with and potentially exacerbate suicidal ideation. These findings provide support to the Interpersonal Theory of Suicide, which suggests that perceived burdensomeness and thwarted belongingness are vital psychological factors in the onset of suicidal ideation. Addressing and intervening in these bridging nodes could help reduce the influence of ACEs on suicide ideation within the MSM community.

Abstract As a critical technology, anomaly detection ensures the smooth operation of cloud systems while maintaining the market competitiveness of cloud service providers. However, the resource data in real-world cloud systems is predominantly unannotated, leading to insufficient supervised signals for anomaly detection. Moreover, complicated topological associations existed between cloud servers (e.g., computation, storage, and communication). While acquiring resource information, correlating the system topology is challenging. To this end, we propose the GCAD for cloud system anomaly detection, which integrates data augmentation, GraphGRU, contrastive learning, and reconstruction. First, GCAD constructs positive and negative sample pairs through the masking and Gaussian noise data augmentation. Then, the GraphGRU processes extended temporal graph data, extracting and fusing spatiotemporal features from resource status and system topology. In addition, GCAD introduces linear attention for encoding spatiotemporal representations to capture their global correlation information. The weight parameters of the encoder are optimized using a contrastive learning mechanism. Finally, GCAD utilizes a reconstruction technique to calculate anomaly scores, facilitating the evaluation of the state of the cloud system at each time point. Experimental results indicate that GCAD outperforms state-of-the-art compared methods on two real-world datasets that contain topology information.

Abstract Multivalent antigen display on nanoparticles can enhance the immunogenicity of nanovaccines targeting viral moieties, such as the receptor binding domain (RBD) of SARS-CoV-2. However, particle morphology and size of current nanovaccines are significantly different from those of SARS-CoV-2. Additionally, surface antigen patterns are not controllable to enable the optimization of B cell activation. Herein, we employ an icosahedral DNA origami (ICO) as a display particle for RBD nanovaccines, achieving morphology and diameter like the virus (91 ± 11 nm). The surface addressability of DNA origami permits facile modification of the ICO surface with numerous RBD antigen clusters (ICO-RBD) to form various antigen patterns. Using an in vitro screening system, we demonstrate that the antigen spacing, antigen copies within clusters and cluster number parameters of the surface antigen pattern all impact the ability of the nanovaccines to activate B cells. Importantly, the optimized ICO-RBD nanovaccines evoke stronger and more enduring humoral and T cell immune responses in female mouse models compared to soluble RBD antigens, and the multivalent display broaden the protection range of B cell responses to more mutant strains. Our vaccines activate similar humoral immunity, observable stronger cellular immunity and more memory immune cells compared to trimeric mRNA vaccines.

In order to solve the problem of high concentration of free ammonia(FA) inhibiting ammonia oxidizing bacteria and causing high concentration of ammonia nitrogen wastewater to be unable biologically treated, natural zeolite was used to alleviate the inhibitory effect of FA. Natural clinoptilolite was added to SBR for partial nitrification treatment of copper-ammonia wastewater with ammonia-nitrogen of 210 mg/L. On the 86th day of operation, the reactor achieved 98.5% of ammonia-nitrogen removal rate at load of 1.105 kg/(m3·d). In-situ biological regeneration during the reaction process ensured the continuous enhancement effect of natural zeolite, with zeolite regeneration rates of 99.0% to 106.3%. Through the analysis of extracellular polymeric substance(EPS) content and composition of sludge, it was found that the increase of influent ammonia-nitrogen led to the increase of EPS content, and protein mass fraction in EPS was increased under the stress of copper ion, which promoted the formation of sludge granulation. High throughput sequencing results showed that Nitrosomonas was the main ammonia-oxidizing functional bacterium genus, with relative abundance varied from 10.3% to 51.7%. Comamonas rapidly increased in the presence of high concentration of ammonia-nitrogen, with relative abundance increasing from 0.6% on the 22nd day to 29.9% on the 86th day. The partial nitrification was strengthened by natural zeolite to realize stable and high-efficient treatment of copper-ammonia wastewater.

Abstract Background In patients with ossification of the posterior longitudinal ligament of the cervical spine (OPLL), high spinal cord signal (HCS) is frequently observed in the spinal cord of the corresponding segment. However, studies on the differences in the improvement of high spinal cord signal due to different surgical approaches are limited. The aim of this study was to investigate the improvement of high spinal cord signal in long and short segments with different choices of surgical approaches. Methods In this study, we conducted a meticulous review of medical records for patients diagnosed with ossification of the posterior longitudinal ligament (OPLL). Demographic variables, including gender, age, and body mass index (BMI), were systematically recorded. We evaluated the severity of neurological impairment using the Japanese Orthopaedic Association (JOA) scores both preoperatively and at multiple postoperative follow-up points. Neurological assessments were complemented by serial magnetic resonance imaging (MRI) T2-weighted imaging (T2WI) to measure the extent of high-signal changes (HCS) in the spinal cord, and the alteration of the HCS was quantified by the SCR (the ratio between the signal intensity value of the HCS region and the signal intensity value of the normal spinal cord region at C7-T1). Results In the short-segment high signal change (HCS) group, comparisons of JOA score improvement (Recovery1) and HCS improvement (CR1) at 6 months postoperatively did not demonstrate significant differences between the surgical approaches (P > 0.05; Table 1). However, at the 2-year follow-up, patients who underwent anterior surgery exhibited significantly greater improvements in both JOA scores (Recovery2) and HCS (CR2), with statistical significance achieved (P 0.05; Table 2). Conclusions In patients with OPLL who present with spinal cord high signal, anterior surgery by resection of the ossified posterior longitudinal ligament and direct decompression is more conducive to regression of small spinal cord high signal and improvement of clinical neurological function if the extent of spinal cord high signal is small.

Abstract This study aims to broaden the morphological scope of SDH-deficient renal cell carcinoma and to assist clinicians and pathologists in better understanding this entity to prevent misdiagnosis. This study used immunohistochemistry staining and the first-generation sequencing Sanger method for gene detection. It retrospectively analysed the clinical pathology, molecular characteristics, biological behaviour, and treatment information of one case of SDH-deficient renal cell carcinoma. The patient was a 57-year-old female with right back pain for more than 20 days and had no personal or family history of kidney tumours. In addition, the tumour cells had clear boundaries in morphology, and residual normal renal tubules could be seen around them. There were also ossification and adipose tissue around the tumour centre. The tumour cells were arranged in a glandular tubular and cord-like manner. Vacuolar and eosinophilic inclusion bodies could be observed in the cytoplasm. The nucleus was regular, the chromatin distribution was fine, and there were no obvious nucleoli. They were low-grade nuclei. In addition, no atypical mitosis or necrosis could been found. Furthermore, immunohistochemistry staining showed SDHB-negative and keratin 20 -positive tumour. Meanwhile, the first-generation sequencing also pointed out the presence of SDHB gene mutations in the tumour. After 12 months of follow-up, there was no evidence of disease recurrence in the patient. SDH-deficient renal cell carcinoma is a rare tumour associated with SDH gene germline mutations, and suspected cases should undergo SDHB immunohistochemistry staining. Most SDH-deficient renal cell carcinomas have a good prognosis, but undifferentiated cases require long-term follow-up.

Abstract The human thermal stress indices and datasets are vital for promoting public health and reducing negative environmental impacts as global climate change and extreme meteorological events increase. The current thermal indices generally use an instantaneous or average value to describe thermal stress which cannot reflect the distribution of thermal comfort conditions over time, and there are no global-scale thermal stress datasets with both 0.1° or higher spatial resolution and hourly temporal resolution available yet. A novel human thermal metric, Thermal Stress Duration (TSD), is proposed to represent the accumulative time of different thermal stress levels within a certain period. A high temporal resolution global gridded dataset of human thermal stress metrics (HiGTS) is presented, which consists of hourly gridded maps of Universal Thermal Climate Index (UTCI), Universal Thermal Stress (UTS), and daily TSD at 0.1° × 0.1° spatial resolution over the global land surface, spanning from January 1, 2000, to December 31, 2023.

The rate of retear after surgical repair remains high. Mesenchymal stem cells (MSCs) have been extensively employed in regenerative medicine for several decades. However, safety and ethical concerns constrain their clinical application. Tendon Stem/Progenitor Cells (TSPCs)-derived exosomes have emerged as promising cell-free therapeutic agents. Therefore, urgent studies are needed to investigate whether TSPC-Exos could enhance tendon-bone healing and elucidate the underlying mechanisms. In this study, TSPC-Exos were found to promote the proliferation, migration, and expression of fibrogenesis markers in BMSCs. Furthermore, TSPC-Exos demonstrated an ability to suppress the polarization of M1 macrophages while promoting M2 macrophage polarization. In a rat model of rotator cuff repair, TSPC-Exos modulated inflammation and improved the histological structure of the tendon-bone interface, the biomechanical properties of the repaired tendon, and the function of the joint. Mechanistically, TSPC-Exos exhibited high expression of miR-21a-5p, which regulated the expression of PDCD4. The PDCD4/AKT/mTOR axis was implicated in the therapeutic effects of TSPC-Exos on proliferation, migration, and fibrogenesis in BMSCs. This study introduces a novel approach utilizing TSPC-Exos therapy as a promising strategy for cell-free therapies, potentially benefiting patients with rotator cuff tear in the future.

High-pressure waterjet-assisted tunnel boring machine (WTBM) is an efficient method for improving the tunneling performance of a tunnel boring machine (TBM) and reducing the wear of its disc cutters in hard rock with high geostresses. Confining pressure directly affects the efficiency of rock breaking and the configuration of the disc cutters. In this study, we evaluated the effect of confining pressure on WTBM rock breaking by developing a self-designed and manufactured experimental system, including confining pressure loading, TBM disc-cutter penetration, and high-pressure waterjet. The macro fracture, acoustic emission (AE), peak normal force drop, and specific energy (SE) were analyzed for four different confining pressures (10, 20, 30, and 35 MPa). The results showed that the cutting depth of the waterjet increased linearly as the waterjet pressure increased and decreased with the gradual increase in the nozzle moving speed. The expansion and development of cracks formed rock debris, and the size of the rock fragments decreased with an increase in confining pressure. When the waterjet pressure was 280 MPa, the nozzle moving velocity was 800 mm/min and the kerf space was 75 mm, which indicated that the confining pressure, which was 23.16 MPa, minimized the cutting SE under this condition. However, regardless of the confining pressure, the maximum normal force of WTBM was less than that of a TBM, whereas the SE of WTBM was less than that of complete TBM cutting mode (CTCM). The average force drop and average drop rate of SE were approximately 25%, and 80%, respectively. The results of this study can inspire the design and mechanism of a TBM assisted by a high-pressure waterjet.

Ectopia lentis (EL), characterised by impaired zonular fibers originating from non-pigmented ciliary epithelial cells (NPCEC), presents formidable surgical complexities and potential risks of visual impairment. Cataract surgery is the only treatment method for EL, but it leads to the loss of accommodative power of the lens post-operatively. Furthermore, the challenge of repairing zonular ligaments in situ remains a significant global issue. Ocular tissue and aqueous humour samples from patients with EL were subjected to RNA sequencing and Olink high-throughput proteomic analysis, revealing the downregulation of pathogenic genes (FBN1, MFAP2) and upregulation of secretory proteins (IL-12, MMP-1). The high expression of FBN1 and MFAP2 in NPCECs suggests their potential as candidates for zonular fiber construction; however, the limited availability of donor sources restricts the feasibility of NPCEC transplantation therapy. The reprogramming and directional differentiation of induced pluripotent stem cells (iPSC) to NPCEC was successfully achieved using the developed biomimetic scaffolds that mimic the microstructures of natural radial zonular fibers. Excitingly, the single injection of induced NPCEC-like cells significantly contributed to restoring and enhancing mechanical properties in zonular fiber structures in a rabbit model with EL. This proposed in situ iPSC-based regeneration technique might serve as an innovative therapeutic strategy for clinical EL patients, reduce the cataract surgery rate, and retain the adjustment capacity of inherent lentis.

Objective The aim of this study is to characterize the deep electrical structure of the Baishawo pegmatite-type deposits, explore the spatial distribution of rare metal mineralization models and ore-conferring carriers, and elucidate the relationship between the location of ore veins to provide a basis for prediction in rare metal mineral exploration. Methods Through the controlled-source audio-geomagnetic method (CSAMT) and the conjugate gradient method of inverse measurement of three exploration profiles, deep hidden rock (ore) bodies were detected. Then, by combining these results with the information from drill holes and elemental geochemical anomalies, a comprehensive analysis was carried out to reveal the distribution of the hidden dikes and the mineralization characteristics. Results The study showed that the concealed pegmatite veins are mainly located in the Lengjiaxi Group, where they are concentrated on the top of the granite body and around tectonic fissures and have burial depths ranging from 50 to 300 m. The geophysical signature of pegmatite vein mineralization is a high-resistance vein-like geologic body intruded from a deep high-resistance body into a shallow low-resistance body. Conclusion The determined distribution and burial depth of concealed pegmatite veins, identified potential concealed veins in the study area, and geophysical characteristics of the pegmatite vein mineralization provide a basis for understanding the formation mechanism of fracture zone-constrained pegmatite veins. Significance The research results provide a scientific basis for follow-up exploration of the Baishawo deposit, reveal the formation mechanism of the pegmatite veins, and provide reliable physical exploration and prediction technology and experience useful for rare metal exploration in northeast Hunan and south China.

Abstract No single treatment significantly reduces the mortality rate and improves neurological outcomes after intracerebral haemorrhage (ICH). New evidence suggests that pyroptosis-specific proteins are highly expressed in the perihaematomal tissues of patients with ICH and that the disulfiram (DSF) inhibits pyroptosis. An ICH model was established in C57BL/6 mice by intracranial injection of collagenase, after which DSF was used to treat the mice. Cell model of ICH was constructed, and DSF was used to treat the cells. HE, TUNEL, Nissl, FJC and IF staining were performed to evaluate the morphology of brain tissues; Western blotting and ELISA were performed to measure the protein expression of NOD-like receptor protein 3 (NLRP3)/Caspase-1/gasdermin D (GSDMD) classical pyroptosis pathway and Toll-likereceptor4 (TLR4)/nuclear factor-kappaB (NF-κB) inflammatory signaling pathway and blood‒brain barrier-associated factoes, and the wet/dry weight method was used to determine the brain water content. The expression of proteins related to the NLRP3/Caspase-1/GSDMD pathway and the TLR4/NF-κB pathway was upregulated in tissues surrounding the haematoma compared with that in control tissues; Moreover, the expression of the blood–brain barrier structural proteins occludin and zonula occludens-1 (ZO-1) was downregulated, and the expression of Aquaporin Protein-4 (AQP4) and matrix metalloprotein 9 (MMP-9) was upregulated. DSF significantly inhibited these changes, reduced the haematoma volume, decreased the brain water content, reduced neuronal death and degeneration and improved neurological function after ICH. ICH activated the classical pyroptosis pathway and TLR4/NF-κB inflammatory pathway, disruped the expression of blood–brain barrier structural proteins, and exacerbated brain injury and neurological dysfunction. DSF inhibited these changes and exerted the therapeutic effects on pathological changes and dysfunction caused by ICH.

Abstract To date, there have been no reports on tertiary lymphoid structures (TLS) in primary adenocarcinoma of jejunum and ileum. In this study, we employed digital pathology image analysis software to classify and quantify TLS, and evaluated the maturity of TLS using immunohistochemistry. Molecular genetics and immunotherapy biomarker detection were performed using next-generation sequencing technology, such as tumor mutational burden (TMB) and microsatellite instability (MSI). The aim of this study was to investigate the presence, location, maturity, association with immunotherapy biomarkers, and prognostic value of TLS in primary adenocarcinoma of jejunum and ileum. Compared to secondary follicle-like TLS (SFL-TLS), intra-tumoral TLS (IT-TLS) were more likely to manifest as early TLS (E-TLS) (P = 0.007). Compared to IT-TLS, SFL-TLS had a higher propensity to occur at the invasive margin (IM) (P = 0.032) and showed a trend towards being more prevalent at the tumor periphery (P = 0.057). In terms of immunotherapy biomarkers, there was a higher trend of IM-TLS density in PD-L1(22C3) score CPS

Abstract Objectives Lung adenocarcinoma (LUAD) continues to pose a significant global health challenge. This research investigates cuproptosis and its association with LUAD progression. Employing various bioinformatics techniques, the study explores the heterogeneity of LUAD cells, identifies prognostic cuproptosis-related genes (CRGs), examines cell-to-cell communication networks, and assesses their functional roles. Methods We downloaded single-cell RNA sequencing data from TISCH2 and bulk RNA sequencing data from TCGA for exploring LUAD cell heterogeneity. Subsequently, “CellChat” package was employed for intercellular communication network analysis, while weighted correlation network analysis was applied for identification of hub CRGs. Further, A cuproptosis related prognostic signature was constructed via LASSO regression, validated through survival analysis, nomogram development, and ROC curves. We assessed immune infiltration, gene mutations, and GSEA of prognostic CRGs. Finally, in vitro experiments were applied to validate CDC25C’s role in LUAD. Results We identified 15 clusters and nine cell type in LUAD. Malignant cells showed active communication and pathway enrichment in “oxidative phosphorylation” and “glycolysis”. Meanwhile, prognostic hub CRGs including PFKP, CDC25C, F12, SIGLEC6, and NLRP7 were identified, with a robust prognostic signature. Immune infiltration, gene mutations, and functional enrichment correlated with prognostic CRGs. In vitro cell experiments have shown that CDC25C-deficient LUAD cell lines exhibited reduced activity. Conclusion This research reveals the heterogeneity of LUAD cells, identifies key prognostic CRGs, and maps intercellular communication networks, providing insights into LUAD pathogenesis. These findings pave the way for developing targeted therapies and precision medicine approaches.

Abstract Objective The diagnostic value of serum human epididymal secretory protein 4 (HE4) for endometrial cancer (EC) was assessed via evidence-based medicine (EBM) and systematic review (SR) methodologies. Methods The Cochrane Library, PubMed, Web of Science, Embase, CBM, CNKI, and Wan Fang databases were searched up to April 1st, 2024, to identify relevant literature. The Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool was utilized to evaluate the quality of the selected studies. The meta-analysis was conducted via RevMan 5.3, STATA 16.1, and Meta-disc software. Results A total of 22 studies comprising 9036 cases (3776 cases in the case group and 5260 cases in the control group) were included. The results revealed that HE4 exhibited a pooled sensitivity of 0.59 [95% CI (0.53, 0.64)], specificity of 0.93 [95% CI (0.88, 0.96)], positive likelihood ratio (PLR) of 6.87 [95% CI (4.57, 10.33)], negative likelihood ratio (NLR) of 0.46 [95% CI (0.39, 0.54)], diagnostic odds ratio (DOR) of 14.36 [95% CI (9.37, 21.17)], and area under the receiver operating characteristic curve (AUC) of 0.78 [95% CI (0.75, 0.82)]. Conclusions Serum HE4 demonstrates high specificity and moderate sensitivity for diagnosing EC, thus serving as a valuable biomarker for clinicians either alone or in conjunction with other tumour markers.

Abstract Colistin is one of the last-resort antibiotics in treating infections caused by multidrug-resistant (MDR) pathogens. Unfortunately, the emergence of colistin-resistant gram-negative strains limit its clinical application. Here, we identify an FDA-approved drug, valnemulin (Val), exhibit a synergistic effect with colistin in eradicating both colistin-resistant and colistin-susceptible gram-negative pathogens both in vitro and in the mouse infection model. Furthermore, Val acts synergistically with colistin in eliminating intracellular bacteria in vitro. Functional studies and transcriptional analysis confirm that the combinational use of Val and colistin could cause membrane permeabilization, proton motive force dissipation, reduction in intracellular ATP level, and suppression in bacterial motility, which result in bacterial membrane disruption and finally cell death. Our findings reveal the potential of Val as a colistin adjuvant to combat MDR bacterial pathogens and treat recalcitrant infections.

Abstract As the first identified multidrug efflux pump in Mycobacterium tuberculosis (Mtb), EfpA is an essential protein and promising drug target. However, the functional and inhibitory mechanisms of EfpA are poorly understood. Here we report cryo-EM structures of EfpA in outward-open conformation, either bound to three endogenous lipids or the inhibitor BRD-8000.3. Three lipids inside EfpA span from the inner leaflet to the outer leaflet of the membrane. BRD-8000.3 occupies one lipid site at the level of inner membrane leaflet, competitively inhibiting lipid binding. EfpA resembles the related lysophospholipid transporter MFSD2A in both overall structure and lipid binding sites and may function as a lipid flippase. Combining AlphaFold-predicted EfpA structure, which is inward-open, we propose a complete conformational transition cycle for EfpA. Together, our results provide a structural and mechanistic foundation to comprehend EfpA function and develop EfpA-targeting anti-TB drugs.

Objective: The aim of the present study is to explore the impact of the tet(A) type I variant (tetA-v1) on its fitness effect in Klebsiella pneumoniae. Methods: Clinical K. pneumoniae strains were utilized as parental strains to generate strains carrying only the plasmid vector (pBBR1MCS-5) or the tetA-v1 recombinant plasmid (ptetA-v1). Antimicrobial susceptibility testing was conducted to estimate the contribution of tetA-v1 to drug resistance. Plasmid stability was evaluated by serial passage over 10 consecutive days in the absence of tigecycline. Biological fitness was examined through growth curve analysis, in vitro competition assays and a neutropenic mouse thigh infection model. Results: A 2–4-fold increase in tigecycline MIC was observed following the acquisition of tetA-v1. Without tigecycline treatment, the stability of ptetA-v1 plasmids has been decreasing since day 1. The ptetA-v1 plasmid in Kp89, Kp91, and Kp93 exhibited a decrease of about 20% compared to the pBBR1MCS-5 plasmid. The acquisition of the tetA-v1 gene could inhibit the growth ability of K. pneumoniae strains both in vitro and in vivo. tetA-v1 gene imposed a fitness cost in K. pneumoniae, particularly in the CRKP strain Kp51, with a W value of approximately 0.56. Conclusion: The presence of tetA-v1 is associated with a significant fitness cost in K. pneumoniae in the absence of tigecycline, both in vitro and in vivo.

Abstract The development of non-noble metal electrocatalysts for the Oxygen Evolution Reaction (OER) is advancing towards the use of multi-element materials. To reveal the complex correlations of multi-element OER electrocatalysts, we developed an iterative workflow combining high-throughput experiments and AI-generated content (AIGC) processes. An increased number of 909 (compared to 145 in previous literature) universal descriptors for inorganic materials science were constructed and used as Artificial Neural Network (ANN) input. A large number of statistical ensembles with each ANN individual ensemble having a reduced number of descriptors were integrated with a new Hierarchical Neural Network (HNN) algorithm. This algorithm addresses the longstanding challenge of balancing overwhelming descriptor numbers with insufficient datasets in traditional ANN approaches to materials science problems. As a result, the combination of AIGC and experimental validation significantly enhanced prediction accuracy, increase the R2 values from 0.7 to 0.98 for Tafel slopes.

Abstract Thyroid cancer (TC) is a significant global healthcare burden. However, the lack of comprehensive data has impeded our understanding of its global impact. We aimed to examine the burden of TC and its trends at the global, regional, and national levels using data stratified by sociodemographic index (SDI), sex, and age. Data on TC, including incidence, mortality, and disability-adjusted life-years (DALYs) from 1990 to 2021, were obtained from the Global Burden of Disease Study 2021. Estimated annual percentage changes (EAPCs) were calculated to assess the incidence rate, mortality, and DALYs trends. The incidence, mortality, and DALYs of TC in 2021 were 249,538 (95% uncertainty interval: 223,290–274,638), 44,799 (39,925–48,541), and 646,741 (599,119–717,357), respectively. The age-standardized incidence rate (ASIR) in 2021 was 2.914 (2.607–3.213), with an EAPC of 1.25 (1.14–1.37) compared to 1990. In 2021, the age-standardized death rate (ASDR) was 0.53 (0.47–0.575) and age-standardized DALYs rate was 14.571 (12.783–16.115). Compared with 1990, the EAPCs of ASDR and age-standardized DALYs rate showed decreasing trends, at − 0.24 (− 0.27 to − 0.21) and − 0.14 (− 0.17 to − 0.11), respectively. Low SDI regions showed the highest ASDR and age-standardized DALYs rate, at 0.642 (0.516–0.799) and 17.976 (14.18–23.06), respectively. Low-middle SDI regions had the highest EAPCs for ASDR and age-standardized DALYs rate, at 0.74 (0.71–0.78) and 0.67 (0.63–0.7), respectively. Females exhibited decreasing trend in ASDR and age-standardized DALYs rate, with EAPCs of − 0.58 (− 0.61 to − 0.55) and − 0.45 (− 0.47 to − 0.42), respectively. In contrast, males showed an increasing trend in ASDR and age-standardized DALYs rate, with EAPCs of 0.41 (0.35–0.46) for both. In high-income regions, most countries with decreased annual changes in deaths experience increasing age-related deaths. Over the past few decades, a notable increase in TC incidence and decreased mortality has been observed globally. Regions characterized by lower SDI, male sex, and an aging population exhibited no improvement in TC mortality. Effective resource allocation, meticulous control of risk factors, and tailored interventions are crucial for addressing these issues.

Abstract Recent advancements in cancer research have led to the generation of innovative nanomaterials for improved diagnostic and therapeutic strategies. Despite the proven potential of two-dimensional (2D) molybdenum disulfide (MoS2) as a versatile platform in biomedical applications, few review articles have focused on MoS2-based platforms for cancer theranostics. This review aims to fill this gap by providing a comprehensive overview of the latest developments in 2D MoS2 cancer theranostics and emerging strategies in this field. This review highlights the potential applications of 2D MoS2 in single-model imaging and therapy, including fluorescence imaging, photoacoustic imaging, photothermal therapy, and catalytic therapy. This review further classifies the potential of 2D MoS2 in multimodal imaging for diagnostic and synergistic theranostic platforms. In particular, this review underscores the progress of 2D MoS2 as an integrated drug delivery system, covering a broad spectrum of therapeutic strategies from chemotherapy and gene therapy to immunotherapy and photodynamic therapy. Finally, this review discusses the current challenges and future perspectives in meeting the diverse demands of advanced cancer diagnostic and theranostic applications. Graphical Abstract

Abstract Perineural invasion (PNI) is a new approach of cervical cancer invasion and metastasis, involving the cross-talk between tumor and nerve. However, the initiating signals and cellular interaction mechanisms of PNI remain largely elusive. The nerve-sparing radical hysterectomy (NSRH) proposed to improve postoperative quality of life is only applicable to cervical cancer patients without PNI. Therefore, it is important to elucidate the underlying mechanisms initiating PNI, and suggest the effective biomarkers to predict PNI before NSRH surgery. Here, we found that PNI is the characteristic of advanced cervical cancer, and Schwann cells were the antecedent cells that initiating PNI. Further, neuropeptide neuromedin B (NMB) produced by cervical cancer cells was determined to induce PNI by reprogramming Schwann cells, including driving their morphological and transcriptional changes, promoting their proliferation and migration, and initiating PNI by secreting CCL2 and directing axon regeneration. Mechanistically, cervical cancer cells-produced NMB activated its receptor NMBR in Schwann cells, and opened the T-type calcium channels to stimulate Ca2+ influx through PKA signaling, which could be blocked by the inhibitor. Clinically, combined examination of serum NMB and CCL2 levels was suggested to effectively predict PNI in cervical cancer patients. Our data demonstrate that cervical cancer-produced NMB initiates the reprograming of Schwann cells, which then direct axon regeneration, thus causing PNI onset. The elevated serum NMB and CCL2 levels may be useful for the decision-making to nerve sparing during hysterectomy surgery of cervical cancer patients.

Abstract Circular RNAs (circRNAs) are unique noncoding RNAs that have a closed and stable loop structure generated through backsplicing. Due to their conservation, stability and tissue specificity, circRNAs can potentially be used as diagnostic indicators and therapeutic targets for certain tumors. Many studies have shown that circRNAs can act as microRNA (miRNA) sponges, and engage in interactions with proteins and translation templates to regulate gene expression and signal transduction, thereby participating in the occurrence and development of a variety of malignant tumors. Immunotherapy has revolutionized the treatment of cancer. Early researches have indicated that circRNAs are involved in regulating tumor immune microenvironment and antitumor immunity. CircRNAs may have the potential to be important targets for increasing sensitivity to immunotherapy and expanding the population of patients who benefit from cancer immunotherapy. However, few studies have investigated the correlation between circRNAs and tumor immunity. In this review, we summarize the current researches on circRNAs involved in antitumor immune regulation through different mechanisms and their potential value in increasing immunotherapy efficacy with the goal of providing new targets for cancer immunotherapy.

Abstract Load prediction tasks aim to predict the dynamic trend of future load based on historical performance sequences, which are crucial for cloud platforms to make timely and reasonable task scheduling. However, existing prediction models are limited while capturing complicated temporal patterns from the load sequences. Besides, the frequently adopted global weighting strategy (e.g., the self-attention mechanism) in temporal modeling schemes has quadratic computational complexity, hindering the immediate response of cloud servers in complex real-time scenarios. To address the above limitations, we propose a Wavelet decomposition-enhanced External Transformer (WETformer) to provide accurate yet efficient load prediction for cloud servers. Specifically, we first incorporate discrete wavelet transform to progressively extract long-term trends, highlighting the intrinsic attributes of temporal sequences. Then, we propose a lightweight multi-head External Attention (EA) mechanism to simultaneously consider the inter-element relationships within load sequences and the correlations across different sequences. Such an external component has linear computational complexity, mitigating the encoding redundancy prevalent and enhancing prediction efficiency. Extensive experiments conducted on Alibaba Cloud’s cluster tracking dataset demonstrate that WETformer achieves superior prediction accuracy and the shortest inference time compared to several state-of-the-art baseline methods.

Abstract Melanoma is one of the most prevalent skin cancers, with high metastatic rates and poor prognosis. Understanding its molecular pathogenesis is crucial for improving its diagnosis and treatment. Integrated analysis of multi-omics data from 207 treatment-naïve melanomas (primary-cutaneous-melanomas (CM, n = 28), primary-acral-melanomas (AM, n = 81), primary-mucosal-melanomas (MM, n = 28), metastatic-melanomas (n = 27), and nevi (n = 43)) provides insights into melanoma biology. Multivariate analysis reveals that PRKDC amplification is a prognostic molecule for melanomas. Further proteogenomic analysis combined with functional experiments reveals that the cis-effect of PRKDC amplification may lead to tumor proliferation through the activation of DNA repair and folate metabolism pathways. Proteome-based stratification of primary melanomas defines three prognosis-related subtypes, namely, the ECM subtype, angiogenesis subtype (with a high metastasis rate), and cell proliferation subtype, which provides an essential framework for the utilization of specific targeted therapies for particular melanoma subtypes. The immune classification identifies three immune subtypes. Further analysis combined with an independent anti-PD-1 treatment cohort reveals that upregulation of the MAPK7-NFKB signaling pathway may facilitate T-cell recruitment and increase the sensitivity of patients to immunotherapy. In contrast, PRKDC may reduce the sensitivity of melanoma patients to immunotherapy by promoting DNA repair in melanoma cells. These results emphasize the clinical value of multi-omics data and have the potential to improve the understanding of melanoma treatment.

Objective To analyze the accuracy of the new generation intraocular lens (IOL) formula and the Wang-Koch (WK) adjustment in individuals with severe myopia undergoing combined anterior-posterior surgery. Methods A total of 100 patients (100 eyes) with axial length (AL) >26 mm undergoing combined anterior and posterior segment surgery in our department from June 2015 to June 2021 were enrolled in this study. Totally 13 IOL calculation formulas, such as Barrett Universal Ⅱ (BUⅡ), Emmetropia Verifying Optical (EVO), Kane, Haigis, Hoffer Q, Holladay, and SRK/T as well as the first generation linear WK eye axis optimization formula (Haigis-WK1, SRK/T-WK1, Hoffer Q-WK1, Holladay 1-WK1) and the second generation linear WK eye axis optimization formula (SRK/T-WK2, Holladay 1-WK2), were utilized to determine IOL diopter. The mean prediction error (ME), mean absolute error (MAE), median absolute error (MedAE), and percentage of prediction error within different refractive thresholds were calculated to assess the accuracy of each formula. In order to investigate the impact of AL on accuracy of IOL calculation, the patients were categorized into group A (38 eyes, 26.00 mm < AL≤28.00 mm), group B (28 eyes, 28.00 mm < AL≤30.00 mm), and group C (34 eyes, AL >30.00 mm). Additionally, the patients were also divided into silicone oil (63 eyes) and non-silicone oil (37 eyes) groups based on preoperative intraocular filling to determine the effect of intraocular filling on IOL calculation. Results The MedAE values of the new-generation IOL formulas (BUⅡ, EVO, and Kane) were significantly lower (0.34D, 0.31D, 0.35D) than those of traditional formulas (P < 0.05). Additionally, the percentage of prediction errors within ±0.25 D, ±0.50 D, ±0.75 D, and ±1.00 D were significantly higher with the new formulas when compared to traditional ones (P < 0.05). Traditional formulas exhibited a hyperopic deviation (0.35D~0.65 D), which could be corrected using the WK eye axis adjustment. WK2 was effective in improving the accuracy of calculation in SRK/T and Holladay 1 formulas, and there was no statistical difference in the MedAE values of SRK/T-WK2 and Holladay 1-WK2 formulas with the new-generation IOL formulas. When comparing the formulas across different axial eye length groups in terms of MedAE, the new IOL formulas (BUⅡ, kane and EVO) and WK-corrected formulas (Haigis-WK1, SRK/T-WK1, SRK/T-WK2, Hoffer Q-WK1, Holladay 1-WK1, Holladay 1-WK2) showed no significant differences among the different AL groups. However, there were significant differences in the MedAE values of traditional formulas among the different AL groups (P < 0.01), with group C displaying the largest MedAE values (Haigis: 0.84D, SRK/T: 1.10D, Hoffer Q: 1.23D, Holladay 1: 1.20D). Comparing the MedAE values of different formulas in various preoperative intraocular filling groups, it was observed that the MedAE values of the new-generation IOL formulas (BUⅡ, kane and EVO), Haigis, and SRK/T formulas were significantly higher in the silicone oil-filled eye group than the non-silicone oil-filled eye group (P < 0.05). Conclusion In patients with high myopia undergoing combined anterior and posterior segment surgery, the precision and consistency of the new-generation IOL formulas and the second-generation linear WK axis correction formula exhibit significant improvements when compared to traditional formulas.

Abstract Multi‐omics studies of breast ductal carcinoma (BRDC) have advanced the understanding of the disease's biology and accelerated targeted therapies. However, the temporal order of a series of biological events in the progression of BRDC is still poorly understood. A comprehensive proteogenomic analysis of 224 samples from 168 patients with malignant and benign breast diseases is carried out. Proteogenomic analysis reveals the characteristics of linear multi‐step progression of BRDC, such as tumor protein P53 (TP53) mutation‐associated estrogen receptor 1 (ESR1) overexpression is involved in the transition from ductal hyperplasia (DH) to ductal carcinoma in situ (DCIS). 6q21 amplification‐associated nuclear receptor subfamily 3 group C member 1 (NR3C1) overexpression helps DCIS_Pure (pure DCIS, no histologic evidence of invasion) cells avoid immune destruction. The T‐cell lymphoma invasion and metastasis 1, androgen receptor, and aldo‐keto reductase family 1 member C1 (TIAM1‐AR‐AKR1C1) axis promotes cell invasion and migration in DCIS_adjIDC (DCIS regions of invasive cancers). In addition, AKR1C1 is identified as a potential therapeutic target and demonstrated the inhibitory effect of aspirin and dydrogesterone as its inhibitors on tumor cells. The integrative multi‐omics analysis helps to understand the progression of BRDC and provides an opportunity to treat BRDC in different stages.

The coastal regions of the China–Pakistan Economic Corridor (CPEC) are crucial links for the “21st Century Maritime Silk Road”. Nonetheless, this region is facing significant ecological challenges due to natural disasters and intensive human activity. To effectively monitor and assess the ecological health of these critical coastal zones, this study employed integrated labels and a deep learning model to obtain land cover data spanning from 2000 to 2023. It then constructed a vigour-organisation-resilience (VOR) model with 12 assessment indicators to evaluate the landscape ecological health of this region. The evaluation results showed distinct spatial patterns. Gwadar and Ormara’s “Bare land” areas remained “Sick,” while Karachi and Lower Indus’ “Impervious surfaces” were “Unhealthy” with minimal fluctuations. The Lower Indus region saw “Sub-healthy” expansion with increased “Crops” areas. Lasbela was “Healthy,” dominated by shrub-based “Other vegetation,” and the Indus Delta’s mangroves maintained a “Very healthy” state. Overall, the CPEC coastal regions were rated “Unhealthy,” with signs of moderate improvement. We recommend that the CPEC coastal areas focus on restoring “Sick” areas, promoting sustainable agriculture in “Sub-healthy” regions, and conserving “Healthy” and “Very healthy” areas. This study demonstrates the efficacy of deep learning and VOR model in assessing long-term ecological health, providing a valuable framework that can be applied in other coastal regions facing similar challenges.

The transformation and upgrading of the industrial structure constitute a pivotal task for sustainable economic development, and the factors influencing this process are also of concern to developing countries around the world. Unfortunately, there is still relatively little systematic discussion on the impact of environmental policy on the industrial structure. Against this backdrop, we have employed the multi-period differences-in-differences (DID) model to assess the impact of the implementation of the National Key Ecological Function Area (NKEFA) policy on the industrial structure in the Yellow River Basin. Our findings reveal that this environmental policy fosters the advancement of industrial structure but does not influence its rationalisation. Regarding mediating effects, we confirm the positive impacts of population density and the investment in education. Furthermore, the policy effects are more pronounced in non-ethnic provinces with better basic conditions, whereas ethnic provinces exhibit almost no effect. The policy effects are more significant in large cities than in small and medium-sized cities. These findings enrich the existing exploration of the impact of environmental policy on industrial structure and provide a strong reference for policy practice in developing countries.

RationaleKidney inflammation plays a crucial role in the pathogenesis of IgA nephropathy (IgAN), yet the specific phenotypes of immune cells involved in disease progression remain incompletely understood. Utilizing joint profiling through longitudinal single-cell RNA-sequencing (scRNAseq) and single-cell assay for transposase-accessible chromatin sequencing (scATACseq) can provide a comprehensive framework for elucidating the development of cell subset diversity and how chromatin accessibility regulates transcription.ObjectiveWe aimed to characterize the dynamic immune cellular landscape at a high resolution in an early IgAN mouse model with acute kidney injury (AKI).Methods and resultsA murine model was utilized to mimic 3 immunological states –”immune stability (IS), immune activation (IA) and immune remission (IR)” in early human IgAN-associated glomerulopathy during AKI, achieved through lipopolysaccharide (LPS) injection. Urinary albumin to creatinine ratio (UACR) was measured to further validate the exacerbation and resolution of kidney inflammation during this course. Paired scRNAseq and scATACseq analysis was performed on CD45+ immune cells isolated from kidney tissues obtained from CTRL (healthy vehicle), IS, IA and IR (4 or 5 mice each). The analyses revealed 7 major cell types and 24 clusters based on 72304 single-cell transcriptomes, allowing for the identification and characterization of various immune cell types within each cluster. Our data offer an impartial depiction of the immunological characteristics, as the proportions of immune cell types fluctuated throughout different stages of the disease. Specifically, these analyses also revealed novel subpopulations, such as a macrophage subset (Nlrp1b Mac) with distinct epigenetic features and a unique transcription factor motif profile, potentially exerting immunoregulatory effects, as well as an early subset of Tex distinguished by their effector and cytolytic potential (CX3CR1-transTeff). Furthermore, in order to investigate the potential interaction between immune cells and renal resident cells, we conducted single-cell RNA sequencing on kidney cells obtained from a separate cohort of IS and IA mice without isolating immune cells. These findings underscored the diverse roles played by macrophages and CD8+ T cells in maintaining homeostasis of endothelial cells (ECs) under stress.ConclusionsThis study presents a comprehensive analysis of the dynamic changes in immune cell profiles in a model of IgAN, identifying key cell types and their roles and interactions. These findings significantly contribute to the understanding of the pathogenesis of IgAN and may provide potential targets for therapeutic intervention.

Lipid droplets (LDs) are organelles associated with lipid storage and energy metabolism, thus, their morphology and quantity are of significant research interest. While commercially available BODIPY dye effectively labels LDs in various cell types, it also labels lysosome-related organelles (LROs) in C. elegans, leading to non-specific LD quantification. Here, we report that the fluorescent signals of BODIPY exhibit distinct fluorescence lifetime patterns for LROs and LDs, which can be captured, visualized, and filtered by fluorescence lifetime imaging microscopy. Furthermore, we proposed and validated a method based on fluorescence lifetime that can improve the accuracy of fat storage quantification in BODIPY vital-staining worms, which holds broad applications, including rapid and accurate LD quantification in forward genetic screening. Additionally, our method enables observing dynamic LD-LRO interactions in living worms, a unique capability of BODIPY vital staining. Our findings highlight distinct BODIPY fluorescence lifetime characteristics of LDs and LROs, providing a valuable tool for future research on LDs, LROs, or their interactions.

Photodynamic therapy (PDT) can produce high levels of reactive oxygen species (ROS) to kill tumor cells and induce antitumor immunity. However, intracellular antioxidant systems, including glutathione (GSH) system and thioredoxin (Trx) system, limit the accumulation of ROS, resulting in compromised PDT and insufficient immune stimulation. Herein, we designed a nanomedicine PtHPs co-loading photosensitizer pyropheophorbide a (PPa) and cisplatin prodrug Pt–COOH(IV) (Pt (IV)) based on hydroxyethyl starch (HES) to inhibit both GSH and Trx antioxidant systems and achieve potent PDT as well as antitumor immune responses. Specifically, HES-PPa and HES-Pt were obtained by coupling HES with PPa and Pt (IV), and assembled into nanoparticle PtHPs by emulsification method to achieve the purpose of co-delivery of PPa and Pt (IV). PtHPs improved PPa photostability while retaining PPa photodynamic properties. In vitro experiments showed that PtHPs reduced GSH, inhibited Trx system and had better cell-killing effect and ROS generation ability. Subcutaneous tumor models showed that PtHPs had good safety and tumor inhibition effect. Bilateral tumor models suggested that PtHPs promoted the release of damage-associated molecular patterns and the maturation of dendritic cells, induced T cell-mediated immune responses, and thus suppressed the growth of both primary and distal tumors. This study reports a novel platinum-based nanomedicine and provides a new strategy for boosting PDT therapy-mediated antitumor immunity by overcoming intrinsic antioxidant systems.

A simplified two-stage method was employed to provide an explicit solution for the time-dependent tunnel-rock interaction, considering the generalized Zhang-Zhu strength criterion. Additionally, a simplified mechanical model of the yielding support structure was established. The tunnel excavation is simplified to a two-stage process: the first stage is affected by the longitudinal effect, while the second stage is affected by rheological behavior. Two cases are considered: one is that the rigid support is constructed during the first stage, and the other is that constructed at the second stage. Distinguished by the support timing at the seconde stage, different kinds of the “yield-resist combination” support method are divided into three categories: “yield before resist” support, “yield-resist” support, and “control-yield-resist” support. Results show that the support reaction of “control-yield-resist” is much higher than that of “yield before resist” if the initial geostress is not very high, but the effect is not obvious on controlling the surrounding rock deformation. So, the “yield before resist” support is much more economical and practical when the ground stress is not very high. However, under high geostress condition, through applying relatively high support reaction actively to surrounding rock at the first stage, the “control-yield-resist” support is superior in controlling the deformation rate of surrounding rock. Therefore, in the high geostress environment, it is recommended to construct prestressed yielding anchor immediately after excavation, and then construct rigid support after the surrounding rock deformation reaches the predetermined deformation.

Mangroves are among the most carbon-rich ecosystems in the world. However, they have experienced widespread loss due to climate change and have been reclaimed for coastal cropland and aquaculture ponds. Studying the impact of climate change on the potential distribution and carbon benefits of mangroves is crucial for their conservation and restoration. Currently, there is limited research on the potential distribution of mangroves in China under future climate change scenarios using ensemble models. Furthermore, there is a relative scarcity of studies that apply simulation results to the restoration and protection of mangroves. Therefore, based on 15 dominant mangrove species, we constructed high-precision species distribution models to simulate the potential distribution of mangroves in China during the current period (1981–2010) and predicted their potential distribution under three climate scenarios (SSP1-2.6, SSP3-7.0, and SSP5-8.5) in the late 21st century (2071–2100). Our study showed that 1) the four most crucial drivers of mangrove suitability in China are: air temperature in the coldest quarter, sea surface temperature range, isothermality, and annual precipitation amount. 2) mangroves tend to expand northward by 2–2.5 degrees of latitude in the end of the 21st century. Meanwhile, the potential distribution of Spartina alterniflora is expected to expand rapidly and pose a significant competitive threat to native mangrove species; 3) by restoring coastal cropland and aquaculture ponds to mangroves in the potential mangrove distribution area, the potential carbon stocks of mangroves would increase by 178.22–296.44 % and 170.31–277.13 % compared to the current carbon stocks of mangroves, the annual blue carbon would increase by 242.64–262.70 % compared to the current blue carbon of mangroves. Our research could provide valuable information for the future conservation and restoration of mangroves in China.

Metallic sodium (Na) serving as anode for sodium-based batteries (SBBs) has caught much attention, owning to its low electrode potential and high theoretical capacity. However, the notorious Na dendrites severely restrict its practical application in Na metal batteries (SMBs). Herein, the hybrid artificial layer (Na/VN-S) composed of sodium sulfide, vanadium nitride and metal vanadium are constructed on Na anode via pretreatment metallic Na with vanadium nitride and vanadium sulfide powders. The obtained Na/VN-S electrode presents superior electrolyte wettability, high sodiophilicity, low activation energy barrier and high Young’s modulus, leading to homogeneous distribution of Na ions and even Na deposition, so that the Na dendrite growth can be suppressed. Owing to these virtues, the Na/VN-S symmetrical cells present a long cycle life of 1400 h at 0.5 mA cm−2 with 1 mAh cm−2, and can stably cycle at a higher current density of 4 mA cm−2. Moreover, when the commercial Na3V2(PO4)3 (NVP) cathodes are coupled with the Na/VN-S anodes, the Na/VN-S||NVP full cells display a prolonged life of 1900 cycles at 5 C with an outstanding capacity retention of 84.2%. This work contributes to the advancement of Na metal anode in high performance SBBs.

Abstract Aiming at the problem of image classification with insignificant morphological structural features, strong target correlation, and low signal-to-noise ratio, combined with prior feature knowledge embedding, a deep learning method based on ResNet and Radial Basis Probabilistic Neural Network (RBPNN) is proposed model. Taking ResNet50 as a visual modeling network, it uses feature pyramid and self-attention mechanism to extract appearance and semantic features of images at multiple scales, and associate and enhance local and global features. Taking into account the diversity of category features, channel cosine similarity attention and dynamic C-means clustering algorithms are used to select representative sample features in different category of sample subsets to implicitly express prior category feature knowledge, and use them as the kernel centers of radial basis probability neurons (RBPN) to realize the embedding of diverse prior feature knowledge. In the RBPNN pattern aggregation layer, the outputs of RBPN are selectively summed according to the category of the kernel center, that is, the subcategory features are combined into category features, and finally the image classification is implemented based on Softmax. The functional module of the proposed method is designed specifically for image characteristics, which can highlight the significance of local and structural features of the image, form a non-convex decision-making area, and reduce the requirements for the completeness of the sample set. Applying the proposed method to medical image classification, experiments were conducted based on the brain tumor MRI image classification public dataset and the actual cardiac ultrasound image dataset, and the accuracy rate reached 85.82% and 83.92% respectively. Compared with the three mainstream image classification models, the performance indicators of this method have been significantly improved.

Abstract Inositol hexaphosphate (InsP6) is the major storage form of phosphorus in seeds. Reducing seed InsP6 content is a breeding objective in agriculture, as InsP6 negatively impacts animal nutrition and the environment. Nevertheless, how InsP6 accumulation is regulated remains largely unknown. Here, we identify a clade of receptor-like cytoplasmic kinases (RLCKs), named Inositol Polyphosphate-related Cytoplasmic Kinases 1-6 (IPCK1-IPCK6), deeply involved in InsP6 accumulation. The InsP6 concentration is dramatically reduced in seeds of ipck quadruple (T-4m/C-4m) and quintuple (C-5m) mutants, accompanied with the obviously increase of phosphate (Pi) concentration. The plasma membrane-localized IPCKs recruit IPK1 involved in InsP6 synthesis, and facilitate its binding and activity via phosphorylation of GRF 14-3-3 proteins. IPCKs also recruit IPK2s and PI-PLCs required for InsP4/InsP5 and InsP3 biosynthesis respectively, to form a potential IPCK-GRF-PLC-IPK2-IPK1 complex. Our findings therefore uncover a regulatory mechanism of InsP6 accumulation governed by IPCKs, shedding light on the mechanisms of InsP biosynthesis in eukaryotes.

AIM:To compare the corneal refractive power and visual quality after three kinds of corneal refractive surgery: laser subepithelial keratomileusis(LASEK), transepithelial photorefractive keratectomy(TransPRK)and femtosecond laser assisted in situ keratomileusis(FS-LASIK).METHODS: Retrospective study. A total of 232 patients(464 eyes)who underwent elective corneal refractive surgery in our hospital from January 2021 to December 2022 were selected as the study subjects. They were divided into the LASEK group of 70 cases(140 eyes), TransPRK group of 76 cases(152 eyes), and FS-LASIK group of 86 cases(172 eyes)according to the different surgical choices made by the patients. Uncorrected visual acuity(UCVA), visual quality, biomechanical stability, tear film break-up time(BUT), Schirmer Ⅰ test(SⅠt)and quality of life were compared among the three groups at 1 and 3 mo postoperatively.RESULTS: The UCVA of the three groups significantly improved at 1 and 3 mo postoperatively, the total high-order aberrations, spherical aberration, horizontal coma, and vertical coma of the entire cornea were significantly increased, while the biomechanical stability in all three groups were significantly reduced(all P0.05).CONCLUSION:In the treatment of ametropia, LASEK, TransPRK and FS-LASIK all have certain effects, and have similar results in improving UCVA and increasing visual quality. However, TransPRK and LASEK have more stable biomechanical properties than FS-LASIK, and have better efficacy in improving patients' quality of life.

The conventional reservoir automatic history matching method requires multiple computationally time-consuming reservoir numerical simulations. Deep learning agent models can perform alternative reservoir numerical simulation calculations with approximate accuracy and greater computational efficiency. In the reservoir automatic history matching method based on the deep learning agent model， the reservoir uncertainty parameters adjusted by the reservoir automatic history matching method are usually used as the input parameters of the deep learning agent model. Existing deep learning agent models are often single input-output neural network model architectures. They do not consider that reservoir automatic history matching methods require the adjustment of multiple reservoir uncertainty parameters. Multiple deep learning agent models need to be trained to predict water saturation field distribution and pressure field distribution in reservoirs. For solving this problem， a reservoir automatic history matching method based on a dual input-output convolutional neural network agent model was proposed to simultaneously predict the water saturation field distribution and pressure field distribution in a reservoir by using a dual input-output convolutional neural network， with the reservoir permeability field distribution and phase permeability parameters as input. The production was calculated with the help of the Peaceman equation. It was coupled to the ensemble smoother with multiple data assimilation （ES-MDA） methods to invert the reservoir permeability field distribution and phase permeability parameters to achieve a more efficient reservoir automatic history matching solution. The results of the study show that the prediction accuracy of the reservoir water saturation field distribution and pressure field distribution is above 93% at the specified time step based on the dual input-output convolutional neural network agent model. Compared with the traditional reservoir automatic history matching method， the proposed reservoir automatic history matching method based on a dual input-output convolutional neural network agent model avoids the time-consuming computation of multiple calls to the reservoir numerical simulator and improves the efficiency of the matching.

To investigate the effect of magnetic field on the electrochemical corrosion behavior of X70 pipeline steel and the effect of magnetic field on the corrosion behavior of X70 steel after immersed in Kuerle soil simulation solution, the electrochemical corrosion behavior of pipeline steel under different magnetic field strengths, directions and the presence or absence of product films was analyzed by electrochemical tests, immersion tests and metallographic analysis. Results showed that as the magnetic field strength increased, the corrosion rate of X70 steel first increased and then decreased. Changing the direction of the magnetic field had no significant effect on the electrochemical corrosion behavior of X70 steel. The corrosion trend of X70 pipeline steel was the same in both cases after immersed for 3 and 5 d, respectively, and the corrosion rate increased with the increase of external magnetic field. Moreover, the adsorption resistance of X70 steel with a product film on its surface was higher than that without a product film, and the X70 steel with the product film exhibited lower corrosion current density and lighter corrosion degree. However, different immersing times had little effect on the corrosion current density.

Abstract Background The maintenance of mitochondrial homeostasis is critical for tumor initiation and malignant progression because it increases tumor cell survival and growth. The molecular events controlling mitochondrial integrity that facilitate the development of hepatocellular carcinoma (HCC) remain unclear. Here, we report that UBX domain-containing protein 1 (UBXN1) hyperactivation is essential for mitochondrial homeostasis and liver tumorigenesis. Methods Oncogene-induced mouse liver tumor models were generated with the Sleeping Beauty (SB) transposon delivery system. Assessment of HCC cell growth in vivo and in vitro, including tumour formation, colony formation, TUNEL and FACS assays, was conducted to determine the effects of UBXN1 on HCC cells, as well as the involvement of the UBXN1-prohibitin (PHB) interaction in mitochondrial function. Coimmunoprecipitation (Co-IP) was used to assess the interaction between UBXN1 and PHB. Liver hepatocellular carcinoma (LIHC) datasets and HCC patient samples were used to assess the expression of UBXN1. Results UBXN1 expression is commonly upregulated in human HCCs and mouse liver tumors and is associated with poor overall survival in HCC patients. UBXN1 facilitates the growth of human HCC cells and promotes mouse liver tumorigenesis driven by the NRas/c-Myc or c-Myc/shp53 combination. UBXN1 interacts with the inner mitochondrial membrane protein PHB and sustains PHB expression. UBXN1 inhibition triggers mitochondrial damage and liver tumor cell apoptosis. Conclusions UBXN1 interacts with PHB and promotes mitochondrial homeostasis during liver tumorigenesis.

Abstract Efficient allocation of tasks and resources is crucial for the performance of heterogeneous cloud computing platforms. To achieve harmony between task completion time, device power consumption, and load balance, we propose a Graph neural network-enhanced Elite Particle Swarm Optimization (EPSO) model for collaborative scheduling, namely GraphEPSO. Specifically, we first construct a Directed Acyclic Graph (DAG) to model the complicated tasks, thereby using Graph Neural Network (GNN) to encode the information of task sets and heterogeneous resources. Then, we treat subtasks and independent tasks as basic task units while considering virtual or physical devices as resource units. Based on this, we exploit the performance adaptation principle and conditional probability to derive the solution space for resource allocation. Besides, we employ EPSO to consider multiple optimization objectives, providing fine-grained perception and utilization of task and resource information. It also increases the diversity of particle swarms, allowing GraphEPSO to adaptively search for the global optimal solution with the highest probability. Experimental results demonstrate the superiority of our proposed GraphEPSO compared to several state-of-the-art baseline methods on all evaluation metrics.

According to the convergence confinement theory, it is an effective measure to control the large deformation of high ground stress in fractured soft rock tunnels by using yielding support. The yielding support can be classified as either radial or circumferential yielding support. Circumferential yielding support is achieved by transforming radial displacement into circumferential tangential closure without compromising the support capacity of the primary lining support structure. Based on this, and inspired by the design principle of dampers, a yielding support structure system with spring damping elements as its core was developed, based on the connection characteristics of steel arches in highway tunnel, which can provide increasing support resistance in the yielding deformation section. Then the mechanical properties of spring damping elements were obtained through indoor axial pressure and flexural tests. In addition, according to these results with numerical calculations, the yielding support structure system with embedded spring damping elements can reduce the internal force of the support structure by approximately 10% and increase the area of the plastic zone of the surrounding rock by 11.23%, which can fully utilize the self-bearing capacity of surrounding rock and verify the effectiveness of circumferential yielding support. Finally, the spring damping support structure system was designed with reference to the construction process of the tunnel excavated by drilling and blasting method, and the transformation of the spring damping element to spring damping support structure was achieved. Based on field test results, surrounding ground pressure for the yielding support optimization scheme was reduced by 40% and more evenly distributed, resulting in the successful application and a reduction in the construction cost of large deformation tunnels in soft rock.

Abstract The prevalence of chirality, or, handedness in biological world is a fundamental phenomenon and a characteristic hallmark of life. Thus, understanding the origin of enantio-selection, i.e., the sense and magnitude of asymmetric induction, has been a long-pursued goal in asymmetric catalysis. Herein, we demonstrated a polarizability-derived electronic effect that was shown to be capable of rationalizing a broad range of stereochemical observations made in the field of asymmetric catalysis. This effect provided a consistent enantio-control model for the prediction of major enantiomers formed in a ruthenium-catalyzed asymmetric transfer hydrogenations of ketones. Direct and quantitative linear free energy relationships between substrates’ local polarizabilities and observed enantio-selectivity were also revealed in three widely known asymmetric catalytic systems covering both reductions and oxidations. This broadly applicable polarizability-based electronic effect, in conjunction with conventional wisdom mainly leveraging on steric effect considerations, should aid rational design of enantio-selective processes for better production of chiral substances.

Objective To explore the genome-wide distribution of histone H3K27ac in intestinal type gastric cancer, analyze remodeling features of enhancers and regulome and construct a prediction model for prognosis. Methods H3K27ac CUT&Tag sequencing and RNA sequencing were performed in intestinal type gastric cancer tissues from 15 patients and normal gastric mucosa tissues from 18 healthy volunteers. Bioinformatics analysis was performed to identify the differences in genome distribution of H3K27ac modifications. Based on the distribution characteristics of H3K27ac, the enhancer elements were identified and the remodeling characteristics of enhancer and related regulome were explored. The prediction model for prognosis based on enhancer related target genes was constructed by univariate Cox and multivariate Cox regression analyses. Results The histone H3K27ac modification was mainly distributed in the enhancer region and displayed no significant differences in the genomic distribution patterns between normal and cancer tissues. Compared with normal gastric mucosa, the level of enhancer H3K27ac modification was higher in intestinal type gastric cancer. A total of 8 847 enhancers with increased activity in intestinal type gastric cancer were identified, accounting for 8.3% of all enhancers, which might promote malignant behaviors such as proliferation and adhesion of gastric cancer cells. A prognosis-predicting model established based on a panel of 6 genes that upregulated by the acquired enhancer in cancers, which was able to predict the overall survival of patients. Conclusion Enhancer remodeling is one of the significant epigenetic features of intestinal type gastric cancer. These enhancers may drive malignant growth and adhesion of cancer cells by upregulating the expression of MYC, E2F3 and other genes. A prognosis model based on enhancer target genes is constructed.

Background: Immune checkpoint inhibitors (ICIs), especially anti-PD-1/PD-L1 antibodies, have emerged as promising therapeutic options for cervical cancer. However, the efficacy of anti-PD-1 antibody monotherapy is limited. Cryoablation could elicit an anti-tumor immune response, thereby presenting itself as a potential approach to augment the response of ICIs. The aim of our study was to investigate the systemic immunological effects of cryoablation and the potential synergistic anti-tumor effects of cryoablation and anti-PD-1 antibody in cervical cancer. Methods: We established U14 murine bilateral subcutaneous cervical cancer model, wherein the primary tumors were treated with cryoablation. Flow cytometry, immunohistochemistry and RNA-seq were used to analyze the immune cell infiltration and immune-associated pathways in the secondary tumor. Results: Our study revealed that cryoablation reprogrammed the immune landscape, leading to an enhanced infiltration of CD8+ T cell in distant tumors. Cryoablation created a conducive environment for increasing the efficacy of anti-PD-1 immunotherapy. Cryoablation in combination with anti-PD-1 antibody inhibited distant tumors growth and improved mouse survival. Mechanistically, this combination therapy could augment the infiltration of CD8+ T cells, CD4+ T cells, dendritic cells and M1-like tumor-associated macrophages, enhance multiple aspects of antitumor immune response, and reduce immunosuppressive cells such as M2-like tumor-associated macrophages and myeloid-derived suppressor cells in distant tumors. Conclusions: Combination therapy with cryoablation and anti-PD-1 antibody induces an effective abscopal effect in murine model of cervical cancer and may be a novel therapeutic approach for patients with advanced/recurrent cervical cancer.

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

The Maritime Silk Road presents not only great opportunities for development but also enormous challenges to marine ecological security. While, there lacks a systematic assessment of the state of marine ecological security at the regional multi-country scale, which leads to the limited understanding of the marine ecological security from integrated dimensions. This study considered 30 countries along the Maritime Silk Road, constructed marine ecological security assessment indicator system based on Environment-Economy-Society (EES) model, and combined with fuzzy object element model, assessed the spatial and temporal changes of marine ecological security of each country from 2013 to 2019. The results showed that Tanzania has the best state of marine environmental security and Bahrain has the worst state of marine environmental security in terms of marine environmental security. In terms of marine economic security, from 2013 to 2019, there is an upward trend in marine economic security in South Asia. In terms of marine social security, Philippines has the best marine social security, with a security index of 0.787. From the comprehensive assessment results, the marine ecological security situation of the countries along the Maritime Silk Road generally shows an upward trend during the 2013–2019 period. Factors such as the construction of marine protected areas, marine industry, port construction, coastal population numbers, and the number of foreign tourists have significant impacts on marine ecological security. Countries along the Maritime Silk Road should take measures in the areas of marine infrastructure construction, marine ecological restoration and protection, and transboundary cooperation and management in order to promote the sustainable development of marine ecological security in the future.

ABSTRACT: Salmonellosis in poultry is detrimental to the advancement of the breeding industry and poses hazards to human health. Approximately 2,600 Salmonella varieties exist, among which S. Enteritidis, S. Pullorum, S. Typhimurium, and S. Infantis are prevalent serotypes in the poultry industry in recent years. They can also infect humans by contaminating poultry eggs and meat. Therefore, identifying these serotypes is crucial for successful preventive and control interventions. The White–Kauffmann–Le Minor scheme is time-consuming and requires expensive reagents. Whole-genome sequencing (WGS) and other molecular biology techniques require skilled technical staff. In comparison, the polymerase chain reaction (PCR) is more accurate, rapid, and inexpensive, thus proving suitable for widespread application in the poultry industry. Here, we selected 4 specific primers: lygD, mdh, ipaJ, and SIN_02055, which correspond to detecting S. Enteritidis, S. Typhimurium, S. Pullorum, and S. Infantis, respectively. They were integrated into a 1-step multiplex PCR method. We optimized the PCR method by utilizing specificity test results to determine the optimal annealing temperature (57°C). The PCR method exhibited excellent sensitivity for genomic DNA and bacterial cultures. We used the developed method to determine 157 clinical Salmonella isolates from various stages of the poultry production chain. The results aligned with serotype data generated via WGS analysis, demonstrating the method's excellent accuracy. In conclusion, this study developed a 1-step multiplex PCR method that simultaneously identifies S. Enteritidis, S. Typhimurium, S. Pullorum, and S. Infantis, allowing routine mass detection in the grass-root poultry industry.