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Abstract Homotypic cell-in-cell structures (hoCICs) are associated with tumor proliferation, invasion, and metastasis and is considered a promising prognostic marker in various cancers. However, the role of hoCICs in non-small cell lung cancer (NSCLC) remains unclear. Tumor tissue sections were obtained from 411 NSCLC patients. We analyzed the relationship between clinicopathological variables and the number of hoCICs. LASSO and multivariate Cox regression analysis were employed to identify prognostic factors for NSCLC. The impact of hoCICs on overall survival (OS) and disease-free survival (DFS) was assessed using the Kaplan–Meier curves and log-rank test. Prognostic models for OS and DFS were developed and validated using the C-index, time-dependent area under the curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration curves and decision curve analysis (DCA). Among the cohort, 56% of patients had hoCICs while 44% did not. Notably, hoCICs were primarily found at the tumor invasion front. Male gender, smoking, squamous cell carcinoma, low differentiation, tumor size ≥ 3 cm, advanced TNM stage, lymph node metastasis, pleural invasion, vascular invasion, necrosis, P53 mutation, and high expression of Ki-67 were identified as relative risk factors for hoCICs. Furthermore, hoCICs was found to be a significant prognostic factor for both OS and DFS, with higher frequencies of hoCICs correlating with poorer outcomes. We constructed nomograms for predicting 1-, 3-, and 5-year OS and DFS based on hoCICs, and the calibration curves showed good agreement between the predicted and actual outcomes. The results of the C-index, time-dependent AUC, NRI, IDI, and DCA analyses demonstrated that incorporating hoCICs into the prognostic model significantly enhanced its predictive power and clinical applicability. HoCICs indicated independent perdictive value for OS and DFS in patients with NSCLC. Furthermore, the frequent localization of hoCICs at the tumor invasion front suggested a strong association between hoCICs and tumor invasion as well as metastasis.

Abstract Small cell lung cancer (SCLC) constitutes approximately 10% to 15% of all lung cancer diagnoses and represents a pressing global public health challenge due to its high mortality rates. The efficacy of conventional treatments for SCLC is suboptimal, characterized by limited anti-tumoral effects and frequent relapses. In this context, emerging research has pivoted towards immunotherapy combined with chemotherapy, a rapidly advancing field that has shown promise in ameliorating the clinical outcomes of SCLC patients. Through originally developed for non-small cell lung cancer (NSCLC), these therapies have extended new treatment avenues for SCLC. Currently, a nexus of emerging hot-spot treatments has demonstrated significant therapeutic efficacy. Based on the amalgamation of chemotherapy and immunotherapy, and the development of new immunotherapy agents, the treatment of SCLC has seen the hoping future. Progress has been achieved in enhancing the tumor immune microenvironment through the concomitant use of chemotherapy, immunotherapy, and tyrosine kinase inhibitors (TKI), as evinced by emerging clinical trial data. Moreover, a tripartite approach involving immunotherapy, targeted therapy, and chemotherapy appears auspicious for future clinical applications. Overcoming resistance to post-immunotherapy regimens remains an urgent area of exploration. Finally, bispecific antibodies, adoptive cell transfer (ACT), oncolytic virus, monotherapy, including Delta-like ligand 3 (DLL3) and T cell immunoreceptor with Ig and ITIM domains (TIGIT), as well as precision medicine, may present a prospective route towards achieving curative outcomes in SCLC. This review aims to synthesize extant literature and highlight future directions in SCLC treatment, acknowledging the persistent challenges in the field. Furthermore, the continual development of novel therapeutic agents and technologies renders the future of SCLC treatment increasingly optimistic.

Abstract Background Breast cancer (BC) remains the most commonly malignancy among women worldwide. Although early-stage BC typically presents with curative possibilities, advanced-stage disease, especially with metastasis, is significantly limited in terms of effective therapeutic interventions, thereby establishing it as the second leading cause of cancer-related deaths in women. Antibody–Drug Conjugates (ADCs) establish a groundbreaking class of anti-neoplastic agents characterized by high specificity and targeting precision. These agents have been significant in reshaping the therapeutic approach to breast cancer, especially those subtypes with overexpression of the Human Epidermal Growth Factor Receptor 2 (HER2). Comprising monoclonal antibodies, cytotoxic payloads, and conjugative linkers, ADCs function by specifically targeting antigens on cancer cells, thereby facilitating the intracellular delivery of the toxic payload. The present investigation endeavors to synthesize existing primary research outcomes through rigorous bibliometric and data analytical approaches, thereby elucidating the current research landscape, delineating research foci, and identifying potential avenues for future innovation. Methods For bibliometric analysis, a comprehensive data set comprising 2181 entries related to ADCs in breast cancer was retrieved from the Web of Science Core Collection (WoSCC) spanning the years 1999 to 2023. This data was further filtered from the Science Citation Index Expanded (SCI-Expanded). Analysis software tools such as CiteSpace and VOSviewer were employed for multifaceted analyses such as trends of publications, contributions of countries, and burst analytics. In the dimension of clinical trials, we interrogated databases including ClinicalTrials.gov ( https://www.clinicaltrials.gov ) and the WHO International Clinical Trials Registry Platform (ICTRP) ( https://trialsearch.who.int ). A total of 239 clinical trials were initially sourced, among which, 175 were from ClinicalTrials.gov and 64 from ICTRP. After repetitive and correlation-based screening, 119 trials specifically addressing ADC therapeutic strategies in breast cancer were included. Analytical algorithms were executed using Microsoft-based software to evaluate treatment paradigms, emergent research themes, and progress. Results Our investigations signify a growing trend of research on ADCs, with consistent advancements in scientific achievements. The analysis revealed that variables such as economic stratification of nations, healthcare investment paradigms, and disease incidence rates serve as significant determinants in shaping research output. Geographically, the United States emerged as the predominant contributor to the research corpus (36.56%), closely followed by China (21.33%). The underpinning of research accomplishments was found to be significantly bolstered by advancements in molecular biology, immunology, and genetic research. Moreover, the advent of nuclear magnetic resonance diagnostic modalities has contributed saliently to the diagnostic and therapeutic management of breast cancer. Conclusion Our study provides a comprehensive overview of the ADC research landscape through rigorous bibliometric and clinical trial evaluations. At present, the ADC arena has witnessed the successful development and FDA approval of 14 distinct agents, substantially improving the clinical outcomes for a broad spectrum of oncological patients. Future research imperatives may include the exploration of ADCs targeting mutated oncoproteins, dual-specificity ADCs, combination payload strategies, peptide-drug conjugates (PDCs), and non-internalizing ADC modalities. With sustained academic and clinical focus, the ADC domain is poised for transformative advancements in targeted therapeutics across a variety of malignancies.

Changes in structure and properties of resin matrix caused by water absorption is one of the key factors affecting the long-term durability of fiber reinforced polymer composites used in civil engineering. In the present study, the water diffusion and structural change in an epoxy resin were investigated experimentally through immersion in deionized water at 40, 60 and 80 °C for 135 days. Water absorption, thermal, mechanical and microstructure analysis tests were conducted to evaluate the long-term property evolution. It was found that the water absorption of epoxy resin followed a two-stage model, including an initial Fick's diffusion response and a subsequent relaxation response. Long-term hygrothermal exposure brought about the structural change of epoxy resin, which led to the significant degradation up to 8%–30% in the mechanical properties and 21% in glass transition temperature, respectively. The resin plasticization and hydrolysis was the key factors for the degradation of thermal and mechanical properties. It was proved that the plasticization effect was reversible with the remove of bonding water after the drying. Based on the Arrhenius equation, the long-term life of flexural strength in two service environments were predicted to provide the application guideline. The significant degradation of flexural strength was occurred at the initial exposure of 2000 days and then reached to the stable strength retention of 69.6%.

Abstract Background The myeloblastosis (MYB) transcription factor (TF) family is one of the largest and most important TF families in plants, playing an important role in a life cycle and abiotic stress. Results In this study, 268 Avena sativa MYB (AsMYB) TFs from Avena sativa were identified and named according to their order of location on the chromosomes, respectively. Phylogenetic analysis of the AsMYB and Arabidopsis MYB proteins were performed to determine their homology, the AsMYB1R proteins were classified into 5 subgroups, and the AsMYB2R proteins were classified into 34 subgroups. The conserved domains and gene structure were highly conserved among the subgroups. Eight differentially expressed AsMYB genes were screened in the transcriptome of transcriptional data and validated through RT-qPCR. Three genes in AsMYB2R subgroup, which are related to the shortened growth period, stomatal closure, and nutrient and water transport by PEG-induced drought stress, were investigated in more details. The AsMYB1R subgroup genes LHY and REV 1, together with GST, regulate ROS homeostasis to ensure ROS signal transduction and scavenge excess ROS to avoid oxidative damage. Conclusion The results of this study confirmed that the AsMYB TFs family is involved in the homeostatic regulation of ROS under drought stress. This lays the foundation for further investigating the involvement of the AsMYB TFs family in regulating A. sativa drought response mechanisms.

As an emerging technology, digital twin is expected to bring novel application modes to the whole life cycle process of unmanned ground equipment, including research and development, design, control optimization, operation and maintenance, etc. The highly dynamic, complex, and uncertain characteristics of unmanned ground equipment and the battlefield environment also pose new challenges for digital twin technology. Starting from the new challenges faced by the digital twin of unmanned ground equipment, this paper designs a service-oriented cloud-edge-end collaborative platform architecture of the digital twin system of unmanned ground equipment, and further analyzes several key technologies supporting the implementation of the platform architecture.

Abstract Background Cancer recurrence following surgical resection is a major cause of treatment failure. Finding effective methods to prevent postoperative recurrence and wound infection is an important component of successful surgery. With the development of new nanotechnology, more treatment options have been provided for postoperative adjuvant therapy. This study presents an innovative hydrogel system that stimulates tumoricidal immunity after surgical resection of non-small cell lung cancer (NSCLC) and prevents cancer relapse. Results The hydrogel system is based on the excellent photothermal conversion performance of single-atom platinum (CN-Pt) along with the delivery and release of the chemotherapy drug, gemcitabine (GEM). The system is coated onto the wound surface after tumor removal with subsequent near-infrared (NIR) photothermal therapy, which efficiently induces necroptosis of residual cancer cells, amplifies the levels of damage-associated molecular patterns (DAMPs), and increases the number of M1 macrophages. The significantly higher levels of phagocytic macrophages enhance tumor immunogenicity and sensitize cancer cells to CD8 + T-cell immunity to control postoperative recurrence, which has been verified using an animal model of postoperative lung cancer recurrence. The CN-Pt-GEM-hydrogel with NIR can also inhibit postoperative wound infection. Conclusions These findings introduce an alternative strategy for supplementing antitumor immunity in patients undergoing resection of NSCLC tumors. The CN-Pt-GEM-hydrogel with the NIR system also exhibits good biosafety and may be adaptable for clinical application in relation to tumor resection surgery, wound tissue filling, infection prevention, and recurrence prevention.

Bacillus subtilis and Lactobacillus casei were commonly used in the production of fermented bean products. The effects of fermentation by two types of bacteria on the hypoglycemic and lipid-lowering activities of crude polysaccharides from bean flour were analyzed. In this study, 8 kinds of crude polysaccharide samples from fermented edible beans by the two types of bacteria were prepared. And the composition, water solubility, in vitro hypoglycemic and lipid-lowering activity of crude polysaccharides from before and after bean flour fermentation by the two types of bacteria were compared and analyzed. The results showed that the content of uronic acid in the crude polysaccharide from fermented bean flour increased. The content of uronic acid in the crude polysaccharides from fermented bean flour by Bacillus subtilis (4.05%~22.46%) was significantly higher than that of the crude polysaccharides from fermented bean flour by Lactobacillus casei (2.63%~10.72%) (P

Boscalid is a pesticide with the advantages of broad spectrum bactericidal activity, high efficiency, low toxicity, and no cross-resistance with other fungicides currently available on the market. Herein, we report the synthesis of 4′-chloro-2-nitrobiphenyl, a key intermediate of Boscalid using a palladium-catalyzed Suzuki-Miyaura cross-coupling employing the 2-aryl-substituted indenyl phosphine ligand. 4′-Chloro-2-nitrobiphenyl was prepared in 94 % yield on a 100 g scale. This method allows for the industrial production of alimide and active substances bearing a biphenyl moiety.

Abstract Background Breast cancer is a serious threat to women’s health with high morbidity and mortality. The development of more effective therapies for the treatment of breast cancer is strongly warranted. Growing evidence suggests that targeting glucose metabolism may be a promising cancer treatment strategy. We previously identified a new glyceraldehyde-3-phosphate dehydrogenase (GAPDH) inhibitor, DC-5163, which shows great potential in inhibiting tumor growth. Here, we evaluated the anticancer potential of DC-5163 in breast cancer cells. Methods The effects of DC-5163 on breast cancer cells were investigated in vitro and in vivo. Seahorse, glucose uptake, lactate production, and cellular ATP content assays were performed to examine the impact of DC-5163 on cellular glycolysis. Cell viability, colony-forming ability, cell cycle, and apoptosis were assessed by CCK8 assay, colony formation assay, flow cytometry, and immunoblotting respectively. The anticancer activity of DC-5163 in vivo was evaluated in a mouse breast cancer xenograft model. Results DC-5163 suppressed aerobic glycolysis and reduced energy supply of breast cancer cells, thereby inhibiting breast cancer cell growth, inducing cell cycle arrest in the G0/G1 phase, and increasing apoptosis. The therapeutic efficacy was assessed using a breast cancer xenograft mouse model. DC-5163 treatment markedly suppressed tumor growth in vivo without inducing evident systemic toxicity. Micro-PET/CT scans revealed a notable reduction in tumor 18F-FDG and 18F-FLT uptake in the DC-5163 treatment group compared to the DMSO control group. Conclusions Our results suggest that DC-5163 is a promising GAPDH inhibitor for suppressing breast cancer growth without obvious side effects. 18F-FDG and 18F-FLT PET/CT can noninvasively assess the levels of glycolysis and proliferation in tumors following treatment with DC-5163.

Abstract Epstein-Barr virus (EBV) uses a biphasic lifecycle of latency and lytic reactivation to infect >95% of adults worldwide. Despite its central role in EBV persistence and oncogenesis, much remains unknown about how EBV latency is maintained. We used a human genome-wide CRISPR/Cas9 screen to identify that the nuclear protein SFPQ was critical for latency. SFPQ supported expression of linker histone H1, which stabilizes nucleosomes and regulates nuclear architecture, but has not been previously implicated in EBV gene regulation. H1 occupied latent EBV genomes, including the immediate early gene BZLF1 promoter. Upon reactivation, SFPQ was sequestered into sub-nuclear puncta, and EBV genomic H1 occupancy diminished. Enforced H1 expression blocked EBV reactivation upon SFPQ knockout, confirming it as necessary downstream of SFPQ. SFPQ knockout triggered reactivation of EBV in B and epithelial cells, as well as of Kaposi’s sarcoma-associated herpesvirus in B cells, suggesting a conserved gamma-herpesvirus role. These findings highlight SFPQ as a major regulator of H1 expression and EBV latency.

Abstract Adverse perinatal factors can interfere with the normal development of the brain, potentially resulting in long-term effects on the comprehensive development of children. Presently, the understanding of cognitive and neurodevelopmental processes under conditions of adverse perinatal factors is substantially limited. There is a critical need for an open resource that integrates various perinatal factors with the development of the brain and mental health to facilitate a deeper understanding of these developmental trajectories. In this Data Descriptor, we introduce a multicenter database containing information on perinatal factors that can potentially influence children’s brain-mind development, namely, periCBD, that combines neuroimaging and behavioural phenotypes with perinatal factors at county/region/central district hospitals. PeriCBD was designed to establish a platform for the investigation of individual differences in brain-mind development associated with perinatal factors among children aged 3–10 years. Ultimately, our goal is to help understand how different adverse perinatal factors specifically impact cognitive development and neurodevelopment. Herein, we provide a systematic overview of the data acquisition/cleaning/quality control/sharing, processes of periCBD.

Abstract Hematopoiesis ensures tissue oxygenation, and remodeling as well as immune protection in vertebrates. During embryogenesis, hemangioblasts are the source of all blood cells. Gata1a and pu.1 are co-expressed in hemangioblasts before hemangioblasts are differentiated into blood cells. However, the genes that determine the differentiation of hemangioblasts into myeloid or erythroid cell lineages have not been fully uncovered. Here we showed that miRNA-7145, a miRNA with previously unknown function, was enriched in erythrocytes at the definitive wave, but not expressed in myeloid cells. Overexpression and loss-of-function analysis of miRNA-7145 revealed that miRNA-7145 functions as a strong inhibitor for myeloid progenitor cell differentiation while driving erythropoiesis during the primitive wave. Furthermore, we confirmed that cuedc2 is one of miRNA-7145 targeted-genes. Overexpression or knock-down of cuedc2 partially rescues the phenotype caused by miRNA-7145 overexpression or loss-of-function. As well, overexpression and loss-of-function analysis of cuedc2 showed that cuedc2 is required for myelopoiesis at the expense of erythropoiesis. Finally, we found that overexpression of zebrafish cuedc2 in 293 T cell inhibits the JAK1/STAT3 signaling pathway. Collectively, our results uncover a previously unknown miRNA-7145-cuedc2 axis, which regulate hematopoiesis through inhibiting the JAK1/STAT3 signaling pathway.

Using the planar flow casting method to prepare ultra-thin silicon steel ribbons is an eco-friendly and efficient production method. However, the poor wettability between silicon steel and copper result in difficulties in formability by planar flow casting, which limits its application in production of silicon steel ultra-thin ribbons. The process parameters of planar flow casting are the key factors affecting the formability and magnetic properties of non-oriented silicon steel ribbons, in which the wheel speed determines the solidification rate of the silicon steel melt, which has an important influence on the surface quality and magnetic properties of silicon steel ultra-thin ribbons. Therefore, in this paper, the effect of wheel speed on microstructures and magnetic properties of Fe-3.0 wt %Si alloy are systematically investigated. The results indicate that as the wheel speed increases, the grain size and thickness gradually decrease. When the wheel speed is between 10 and 15 m/s, the surface of the ribbons is relatively flat. As the wheel speed increases, the surface quality of ribbons gradually deteriorates. The ribbons were in fragment with the wheel speed of 35 m/s. Compared with the ribbons before annealing, the magnetic induction B50 increased significantly and the iron losses P1.0/400 decreased sharply at 400 Hz after annealing. The magnetic induction of the ribbons after annealing with the wheel speed of 10 m/s reaches to 1.628 T as the wheel speed is 10 m/s with the corresponding iron loss is 16.171 W/kg. The lower lamination factor and micropores of the ribbons may cause the poorer magnetic properties.

Objective(s): Dexmedetomidine (Dex) is a potent α2-adrenergic receptor(α2-AR) agonist that has been shown to protect against sepsis-induced lung injury, however, the underlying mechanisms of this protection are not fully understood. Autophagy and the Smad2/3 signaling pathway play important roles in sepsis-induced lung injury, but the relationship between Dex and Smad2/3 is not clear. This study aimed to investigate the role of autophagy and the Smad2/3 signaling pathway in Dex-mediated treatment of sepsis-induced lung injury. Sepsis was performed using cecal ligation and puncture (CLP) in C57BL/6J mice. Materials and Methods: Mice were randomly assigned to four groups (n=6 per group): sham, CLP, CLP-Dex, and CLP-Dex-YOH, Yohimbine hydrochloride (YOH) is an α2-AR blocker. The cecum was carefully separated to avoid blood vessel damage and was identified and punctured twice with an 18-gauge needle. The pathological changes, inflammatory factor levels, oxidative stress, autophagy, Smad2/3 signaling pathway-related protein levels in lung tissues, and the activity of superoxide dismutase (SOD) and malonaldehyde (MDA) in the serum were measured.Results: CLP-induced lung injury was reflected by increased levels of inflammatory cytokines, apoptosis, and oxidative stress, along with an increase in the expression of autophagy and Smad2/3 signaling pathway-related proteins. Dex could reverse these changes and confer a protective effect on the lung during sepsis. However, the administration of YOH significantly reduced the positive effects of Dex in mice with sepsis.Conclusion: Dex exerts its beneficial effects against sepsis-induced lung injury through the regulation of autophagy and the Smad2/3 signaling pathway.

Abstract Objective To compare the efficacy of ultrasounic-harmonic scalpel and electrocautery in the treatment of axillary lymph nodes during radical surgery for breast cancer. Methods A prospective study was conducted in the Department of Breast Surgery, Zhongda Hospital Affiliated to Southeast University. A total of 128 patients with pathologically confirmed breast cancer who were treated by the same surgeon from July 2023 to November 2023 were included in the analysis. All breast operations were performed using electrocautery, and surgical instruments for axillary lymph nodes were divided into ultrasounic-harmonic scalpel group and electrocautery group using a random number table. According to the extent of lymph node surgery, it was divided into four groups: sentinel lymph node biopsy, lymph node at station I, lymph node at station I and II, and lymph node dissection at station I, II and III. Under the premise of controlling variables such as BMI, age and neoadjuvant chemotherapy, the effects of ultrasounic-harmonic scalpel and electrocautery in axillary surgery were compared. Results Compared with the electrosurgical group, there were no significant differences in lymph node operation time, intraoperative blood loss, postoperative axillary drainage volume, axillary drainage tube indwelling time, postoperative pain score on the day after surgery, and the incidence of postoperative complications (p>0.05). Conclusion There is no significant difference between ultrasounic-harmonic scalpel and electrocautery in axillary lymph node treatment for breast cancer patients, which can provide a basis for the selection of surgical energy instruments.

Abstract Background Gastric cancer is currently estimated to be the fifth leading common cancer in the world, and responsible for about one million new cases and an estimated 769,000 cancer-related deaths each year. WFDC21P is long non-coding RNA and has been reported to play critical roles in serval types of cancer. Our research aims to investigate the biological effects and molecular mechanism of WFDC21P in gastric cancer. Methods Datasets (GSE53137, GSE58828, and GSE109476) in GEO database were used to screen differential expressed lncRNAs in gastric cancer by online GEO2R analysis tool. Quantitative RT-PCR was used to verify the above prediction in ten pairs of gastric cancer and corresponding paracancerous tissues. Pan-cancer analysis was used to analyze the expression of WFDC21P in different types of cancer. Small interfering RNAs were used to WFDC21P knockdown. CCK-8 and colony formation assays were used to measure the proliferation and tumorigenesis abilities. Wound healing and Transwell assay were used to detect the migration and invasion abilities. Proteins that interact with WFDC21P were predicted by catRAPID database. RNA pull down and RNA Immunoprecipitation were used to confirm the interaction. Western blotting was used to detect the key proteins level in calcium homeostasis signaling pathway. Loss-of-function and rescue assays were used to evaluate the biological function of SEC63 at the background of WFDC21P silencing. Results WFDC21P was upregulated in gastric cancer tissues and cell lines. WFDC21P downregulation suppressed proliferation, tumorigenesis, migration, invasion, and promoted apoptosis in gastric cancer. SEC63 protein had the capability to bind with WFDC21P and the expression of SEC63 was regulated by WFDC21P. SEC63 was also upregulated in gastric cancer and exerted effects during tumor growth and metastasis. Conclusions This study confirmed that lncRNA WFDC21P aggravated gastric cancer malignant behaviors by interacting with SEC63 to regulate the calcium homeostasis signaling pathway.

Abstract Background There are two major genetic types of Epstein-Barr Virus (EBV): type 1 (EBV-1) and type 2 (EBV-2). EBV functions by manipulating gene expression in host B cells, using virus-encoded gene regulatory proteins including Epstein-Barr Nuclear Antigen 2 (EBNA2). While type 1 EBNA2 is known to interact with human transcription factors (hTFs) such as RBPJ, EBF1, and SPI1 (PU.1), type 2 EBNA2 shares only ~ 50% amino acid identity with type 1 and thus may have distinct binding partners, human genome binding locations, and functions. Results In this study, we examined genome-wide EBNA2 binding in EBV-1 and EBV-2 transformed human B cells to identify shared and unique EBNA2 interactions with the human genome, revealing thousands of type-specific EBNA2 ChIP-seq peaks. Computational predictions based on hTF motifs and subsequent ChIP-seq experiments revealed that both type 1 and 2 EBNA2 co-occupy the genome with SPI1 and AP-1 (BATF and JUNB) hTFs. However, type 1 EBNA2 showed preferential co-occupancy with EBF1, and type 2 EBNA2 preferred RBPJ. These differences in hTF co-occupancy revealed possible mechanisms underlying type-specific gene expression of known EBNA2 human target genes: MYC (shared), CXCR7 (type 1 specific), and CD21 (type 2 specific). Both type 1 and 2 EBNA2 binding events were enriched at systemic lupus erythematosus (SLE) and multiple sclerosis (MS) risk loci, while primary biliary cholangitis (PBC) risk loci were specifically enriched for type 2 peaks. Conclusions This study reveals extensive type-specific EBNA2 interactions with the human genome, possible differences in EBNA2 interaction partners, and a possible new role for type 2 EBNA2 in autoimmune disorders. Our results highlight the importance of considering EBV type in the control of human gene expression and disease-related investigations.

Abstract Objective The objective of this study is to investigate the impact of four natural product extracts, namely, aloe-emodin, quercetin, curcumin, and tannic acid, on the in vitro bacteriostatic properties and biocompatibility of gentamicin-loaded bone cement and to establish an experimental groundwork supporting the clinical utility of antibiotic-loaded bone cements (ALBC). Methods Based on the components, the bone cement samples were categorized as follows: the gentamicin combined with aloe-emodin group, the gentamicin combined with quercetin group, the gentamicin combined with curcumin group, the gentamicin combined with tannic acid group, the gentamicin group, the aloe-emodin group, the quercetin group, the curcumin group, and the tannic acid group. Using the disk diffusion test, we investigated the antibacterial properties of the bone cement material against Staphylococcus aureus (n = 4). We tested cell toxicity and proliferation using the cell counting kit-8 (CCK-8) and examined the biocompatibility of bone cement materials. Results The combination of gentamicin with the four natural product extracts resulted in significantly larger diameters of inhibition zones compared to gentamicin alone, and the difference was statistically significant (P

Porcine circovirus type 2 (PCV2) infection leads to multi-system inflammation in pigs, and this effect can be achieved by upregulating host miR-21. The underlying mechanism of miR-21 regulates PCV2-induced inflammation is already known, however, how PCV2 regulates miR-21 levels and function using both autonomic and host factors remains to be further revealed. Here we present the first evidence that PCV2 ORF5 induces an inflammatory response by up-regulating miR-21 level through targeting nuclear miR-30d. In this study, we found that overexpression of ORF5 significantly increased miR-21 level and promoted the expression of inflammatory cytokines and activation of the NF-κB pathway, while ORF5 mutation had the opposite effect. Moreover, the differential expression of miR-21 could significantly change the pro-inflammatory effect of ORF5, indicating that ORF5 promotes inflammatory response by up-regulating miR-21. Bioinformatics analysis and clinical detection found that nuclear miR-30d was significantly down-regulated after ORF5 overexpression and PCV2 infection, and targeted pri-miR-21 and PCV2 ORF5. Functionally, we found that miR-30d inhibited the levels of miR-21 and inflammatory cytokines in cells. Mechanistically, we demonstrated that ORF5 inhibits miR-30d expression levels through direct binding but not via the circRNA pathway, and miR-30d inhibits miR-21 levels by targeting pri-miR-21. In summary, the present study revealed the molecular mechanism of ORF5 upregulation of miR-21, further refined the molecular chain of PCV2-induced inflammatory response and elucidated the role of miRNAs in it.

BackgroundCongenital pulmonary sequestration is a rare lung anomaly that can be classified as intralobar pulmonary sequestration or extralobar lung sequestration (ELS). Infradiaphragmatic pulmonary sequestration is a rare type of ELS. Furthermore, intrathoracic kidney (ITK) is a rare disease that can be associated with a congenital diaphragmatic hernia (CHD) in 0.25% of cases. We report the first case of infradiaphragmatic pulmonary sequestration and ITK associated with CDH in a child.Case report and managementThe patient, male, aged 6 months, visited our hospital 2 months prior due to shortness of breath. Based on chest ultrasonography and enhanced computed tomography (CT) examination, infradiaphragmatic pulmonary sequestration and ITK were considered to be associated with CDH. The patient was admitted to our hospital for treatment. After admission, his blood pressure was 85/61 mmHg, there was no hematuria or proteinuria, creatinine was 14 µmol/L, and urea nitrogen was 2.96 mmol/L, all of which showed no abnormalities. A complete preoperative examination was performed prior to surgical treatment. Thoracoscopy revealed that the right kidney had herniated into the chest cavity on the posterolateral side of the diaphragm. The right kidney was returned to the abdominal cavity, the hernia sac was opened, and a bright red lesion tissue with clear boundaries and an abnormal blood vessel supply was observed. After cutting off the abnormal blood vessels, LigaSure TM was used to remove the diseased tissue, and the renal fat sacs and renal tissue were visible. Intermittent suturing of the hernia ring was performed to seal the diaphragmatic hernia. Postoperative pathological examination revealed infradiaphragmatic pulmonary sequestration. The postoperative recovery of the patient was smooth, and a chest CT scan at 2 months showed that the right kidney had returned to the abdominal cavity and the right diaphragm was in the normal position.ConclusionInfradiaphragmatic pulmonary sequestration and ITK associated with CDH is extremely rare. A diagnosis and appropriate surgical planning can be developed using enhanced CT. For infradiaphragmatic pulmonary sequestration located at the top of the hernia sac in CHD, thoracoscopic resection of the infradiaphragmatic pulmonary sequestration and repair of the diaphragmatic hernia is feasible and effective.

Summary: Both concurrent chemoradiotherapy (CCRT) and induction chemotherapy (ICT) followed by CCRT are standard care of advanced nasopharyngeal carcinoma (NPC). However, tailoring personalized treatment is lacking. Herein, we established a radiogenomic clinical decision support system to classify patients into three subgroups according to their predicted disease-free survival (DFS) with CCRT and ICT response. The CCRT-preferred group was suitable for CCRT since they achieved good survival with CCRT, which could not be improved by ICT. The ICT-preferred group was suitable for ICT plus CCRT since they had poor survival with CCRT; additional ICT could afford an improved DFS. The clinical trial–preferred group was suitable for clinical trials since they exhibited poor survival regardless of receiving CCRT or ICT plus CCRT. These findings suggest that our radiogenomic clinical decision support system could identify optimal candidates for CCRT, ICT plus CCRT, and clinical trials, and may thus aid in personalized management of advanced NPC.

Circular RNAs (circRNAs) are a class of non-coding RNAs (ncRNAs) that can participate in biological processes such as gene expression, growth, and development. However, little has been explored about the function of circRNAs in the development of Apis cerana larval guts. By using our previously gained deep sequencing data from the guts of A. cerana worker larvae at 4-, 5-, and 6-day-old (Ac4, Ac5, and Ac6 groups), the expression pattern and regulatory role of circular RNAs (circRNAs) during the development process was comprehensively investigated, with a focus on differentially expressed circRNAs (DEcircRNAs) relevant to immunity pathways and developmental signaling pathways, followed by validation of the binding relationships among a key competing endogenous RNA (ceRNA) axis. Here, 224 (158) DEcircRNAs were detected in the Ac4 vs. Ac5 (Ac5 vs. Ac6) comparison group. It’s suggested that 172 (123) parental genes of DEcircRNAs were involved in 26 (20) GO terms such as developmental process and metabolic process and 138 (136) KEGG pathways like Hippo and Wnt signaling pathways. Additionally, ceRNA network analysis indicated that 21 (11) DEcircRNAs could target seven (three) DEmiRNAs, further targeting 324 (198) DEmRNAs. These DEmRNAs can be annotated to 33 (26) GO terms and 168 (200) KEGG pathways, including 12 (16) cellular and humoral immune pathways (endocytosis, lysosome, Jak-STAT, etc.) and 10 (nine) developmental signaling pathways (Hippo, mTOR, Hedgehog, etc.). Interestingly, DEcircRNAs in these two comparison groups could target the same ace-miR-6001-y, forming complex sub-networks. The results of PCR and Sanger sequencing confirmed the back-splicing sites within four randomly selected DEcircRNAs. RT-qPCR detection of these four DEcircRNAs verified the reliability of the used transcriptome data. The results of dual-luciferase reporter assay verified the binding relationships between novel_circ_001627 and ace-miR-6001-y and between ace-miR-6001-y and apterous-like. Our data demonstrated that DEcircRNAs were likely to modulate the developmental process of the A. cerana worker larval guts via regulation of parental gene transcription and ceRNA network, and novel_circ_001627/ace-miR-6001-y/apterous-like was a potential regulatory axis in the larval gut development. Findings from this work offer a basis and a candidate ceRNA axis for illustrating the circRNA-modulated mechanisms underlying the A. cerana larval guts.

The high performance and long life of engineering structures can be realized through replacing traditional steel materials with glass fiber reinforced polypropylene composites with high toughness/durability, flexibility design and recycling. In addition, the anchorage problem of composites needs to be solved by developing new anchorage technologies or forms. In the present paper, a new type cable-anchor component was developed to prolong the service life and realize the reliable anchoring of composite. The influence mechanism of arc angle (10°, 20°, and 30°) on the mechanical properties of cable-anchor component was evaluated through the experimental and mechanical simulation. The durability evolution of cable-anchor component exposed to alkali solution environment was investigated through macro-performance test and microstructure analysis. The results showed the tensile strength retention of cable-anchor component was up to 88.7 % at the arc angles of 10° under the circumferential constraint of carbon fiber. Larger arc angle increased the stress concentration and fiber misalignment of transition area between arc and straight segments, leading to the formation and propagation of defects or cracks in transition areas and early fracture failure. The saturated water absorption and diffusion coefficient of glass fiber reinforced polypropylene composites were obtained to be 0.78 % and 4.41×10−14 m2/s, respectively. Compared with nylon 6 and epoxy resin, polypropylene has excellent hydrophobic properties with the diffusion coefficient ratio of 0.0077 and 0.024. At the longest immersion, the tensile strength retentions of cable-anchor component were 61.8 % and the failure mode changed from component longitudinal splitting to brittleness fracture of arc region. The degradation mechanism was attributed to the initial defects of arc section formed and expanded under the complex stress and corrosive medium, which further aggravated the fiber/resin interfacial debonding. Through comparing with other glass fiber reinforced thermoplastic and thermosetting composites, the cable-anchor component has higher tensile strength retention after the immersion of alkaline solution owing to excellent hydrophobicity behavior of polypropylene and efficient preparation process.

The bond between fiber-reinforced composites and concrete plays a critical role in reinforcing concrete structures and composite constructions. The study conducts a comprehensive investigation on the uniaxial tensile behavior of steel-reinforced engineered cementitious composites (ECC) and the bond behavior of reinforced ECC-concrete interface. Fifteen steel reinforced ECC specimens were tested under uniaxial load to experimentally evaluate the effect of reinforcement ratio on tensile behavior. Twenty-seven specimens were tested under double-shear conditions to experimentally evaluate the bond behavior of the reinforced ECC-concrete interface. The experimental results demonstrated that the steel reinforcement can significantly improve the ultimate tensile load of ECC and effectively inhibit the generation and propagation of cracks. Furthermore, a simplified model was proposed to predict the uniaxial tensile behavior of steel reinforced ECC. As the reinforcement ratio, width and thickness increased, the bond strength increased, in which the width and thickness serve as the main contributor to the bond strength. Based on the experimental results, a simplified bond-slip constitutive model for the reinforced ECC-concrete interface was proposed by modifying the existing bond-slip constitutive model, which is shown to be able to accurately describe the bond-slip relationship between reinforced ECC and concrete in ascending stage.

In this paper, an experimental and theoretical study on the uniaxial tensile behavior of a fiber-reinforced polymer (FRP) grid-engineered cementitious composite (ECC) composite layer is described. Based on the test parameters, including the ECC material properties, the ECC cross-sectional area and the FRP grid cross-sectional area, three groups of ECC specimens and six groups of composite layer specimens were tested to reveal their joint action mechanism and tensile behavior. The experimental results showed two failure modes: fibers were pulled off or pulled out in the ECC specimens, and in the composite layer specimens, part of the fiber bars in the FRP grid was pulled off. The stress–strain curves show three stages: the elastic stage, softening stage and hardening stage. Due to the reinforcement of the FRP grid, the ultimate stress of the composite layer increased significantly compared with that of the ECC specimens. The composite layer softening strain was primarily related to the ECC softening strain, and the ultimate strain was primarily related to the FRP grid fracture strain. Moreover, a three-stage model was proposed to predict the stressstrain relationship, exhibiting a higher prediction accuracy and smaller dispersion compared with the three existing models.

Leaf inclination angle (LIA) and tillering impact the winter wheat (Triticum aestivum L.) population canopy structure. Understanding their effects on water use (WU) parameters and yield can guide water-saving strategies through population control. In this study, six near-isogenic lines (NILs) and their parents were selected as materials. These special materials were characterized by varying tillering at the current sowing density, a similar genetic background, and, particularly, a gradient in mean flag leaf LIA. The investigation focused on the jointing to early grain-filling stage, the peak water requirement period of wheat crops. Population-scale transpiration (PT) and evaporation from the soil surface (E) were partitioned from total evapotranspiration (ET) by the means of micro-lysimeters. The results showed decreased PT, E, and ET with increased population density (PD) within a narrow density range derived from varying tillering across genotypes. Significant correlations existed between PD and ET, E, and PT, especially in the wettest 2017–2018 growing season. Within such narrow PD range, all the correlations between WU parameters and PD were negative, although some correlations were not statistically significant, thereby suggesting the population structure’s predominant impact. No significant correlation existed between LIA and both ET and PT within the LIA range of 35°–65°. However, significant correlations occurred between LIA and E in two growing seasons. Genotypes with similar LIA but different PD produced varied ET; while with similar PD, the four pairs of genotypes with different LIA each consumed similar ET, thus highlighting PD’s more crucial role in regulating ET. The yield increased with higher LIA, and showed a significant correlation, emphasizing the LIA’s significant effect on yield. However, no correlation was observed with PD, indicating the minor effect of tillering at the current sowing density. Therefore these results might offer valuable insights for breeding water-saving cultivars and optimizing population structures for effective field water conservation.

BackgroundExcessive sodium and low potassium intake are involved in the development of hypertension. Growing evidence showed that the sodium-to-potassium ratio (Na/K) was significantly associated with blood pressure (BP). However, studies on the dose-response relationship of spot urinary Na/K ratio with hypertension and BP in the general population are scarce, especially in the Chinese population.Materials and methodsData from the post-intervention survey of the Shandong Ministry of Health Action on Salt and Hypertension (SMASH) project was analyzed. Associations between Na/K molar ratio and hypertension prevalence and between Na/K molar ratio and BP indices were analyzed using multivariable logistic and linear regression, respectively, followed by subgroup analysis and interaction analysis. The restricted cubic spline model was used to explore the dose–response relationship. Informed by existing literature, we adjusted for potential confounding factors, including temperature and renal function, to assess the association and dose–response relationship.ResultsThere was a non-linear positive association between Na/K and hypertension (OR:1.09, 95%CI: 1.08–1.11) and a linear positive association between Na/K and systolic BP, diastolic BP, and mean arterial pressure (β 0.53, 95%CI: 0.45–0.60; β 0.36, 95%CI: 0.31–0.41; and β 0.42, 95%CI: 0.36–0.47, respectively). The association was stronger in individuals with hypertension, female patients, those in the 50–59-year age group, and those who were obese. Environmental temperatures had little impact on associations.ConclusionOur findings provide further evidence that the spot urinary Na/K ratio is a simple, useful, and convenient indicator for monitoring salt reduction and potassium increase, which could be used in clinical and public health practices.

Preterm infants face a high risk of various complications, and their gut microbiota plays a pivotal role in health. Delivery modes have been reported to affect the development of gut microbiota in term infants, but its impact on preterm infants remains unclear. Here, we collected fecal samples from 30 preterm infants at five-time points within the first four weeks of life. Employing 16 S rRNA sequencing, principal coordinates analysis, the analysis of similarities, and the Wilcoxon rank-sum test, we examined the top dominant phyla and genera, the temporal changes in specific taxa abundance, and their relationship with delivery modes, such as Escherichia-Shigella and Enterococcus based on vaginal delivery and Pluralibacter related to cesarean section. Moreover, we identified particular bacteria, such as Taonella, Patulibacter, and others, whose proportions fluctuated among preterm infants born via different delivery modes at varying time points, as well as the microbiota types and functions. These results indicated the influence of delivery mode on the composition and function of the preterm infant gut microbiota. Importantly, these effects are time-dependent during the early stages of life. These insights shed light on the pivotal role of delivery mode in shaping the gut microbiota of preterm infants and have significant clinical implications for their care and management.

Abstract Background Thyroid cancer is a leading endocrine malignancy, with anaplastic and medullary subtypes posing treatment challenges. Existing therapies have limited efficacy, highlighting a need for innovative approaches. Methods We analyzed 658 articles and 87 eligible clinical trials using bibliometric tools and database searches, including annual publication and citation trends, were executed using Web of Science, CiteSpace, and VOS Viewer. Results Post-2018, there is a surge in thyroid cancer immunotherapy research, primarily from China and the University of Pisa. Of the 87 trials, 32 were Phase I and 55 were Phase II, mostly exploring combination therapies involving immune checkpoint inhibitors. Conclusion The study's dual approach verifies the swift advancement of thyroid cancer immunotherapy from diverse perspectives. Immune checkpoint inhibitors have become the preferred regimen for advanced MTC and ATC in late therapeutic lines. However, since ICB plays a pivotal role in ATC, current clinical trial data show that ATC patients account for more and the curative effect is more accurate. Anticipated future developments are inclined toward combination regimens integrating immunotherapy with chemotherapy or targeted therapies. Emerging approaches, such as bispecific antibodies, cytokine-based therapies, and adoptive cell therapies like CAR-T and TCR-T, are exhibiting considerable potential. Upcoming research is expected to concentrate on refining the tumor immune milieu and discovering novel biomarkers germane to immunotherapeutic interventions.

Abstract Background The global cellular landscape of the tumor microenvironment (TME) combining primary and metastatic liver tumors has not been comprehensively characterized. Methods Based on the scRNA-seq and spatial transcriptomic data of non-tumor liver tissues (NTs), primary liver tumors (PTs) and metastatic liver tumors (MTs), we performed the tissue preference, trajectory reconstruction, transcription factor activity inference, cell–cell interaction and cellular deconvolution analyses to construct a comprehensive cellular landscape of liver tumors. Results Our analyses depicted the heterogeneous cellular ecosystems in NTs, PTs and MTs. The activated memory B cells and effector T cells were shown to gradually shift to inhibitory B cells, regulatory or exhausted T cells in liver tumors, especially in MTs. Among them, we characterized a unique group of TCF7+ CD8+ memory T cells specifically enriched in MTs that could differentiate into exhausted T cells likely driven by the p38 MAPK signaling. With regard to myeloid cells, the liver-resident macrophages and inflammatory monocyte/macrophages were markedly replaced by tumor-associated macrophages (TAMs), with TREM2+ and UBE2C+ TAMs enriched in PTs, while SPP1+ and WDR45B+ TAMs in MTs. We further showed that the newly identified WDR45B+ TAMs exhibit an M2-like polarization and are associated with adverse prognosis in patients with liver metastases. Additionally, we addressed that endothelial cells display higher immune tolerance and angiogenesis capacity, and provided evidence for the source of the mesenchymal transformation of fibroblasts in tumors. Finally, the malignant hepatocytes and fibroblasts were prioritized as the pivotal cell populations in shaping the microenvironments of PTs and MTs, respectively. Notably, validation analyses by using spatial or bulk transcriptomic data in clinical cohorts concordantly emphasized the clinical significance of these findings. Conclusions This study defines the ontological and functional heterogeneities in cellular ecosystems of primary and metastatic liver tumors, providing a foundation for future investigation of the underlying cellular mechanisms.

Objective: Few studies use all nodule burdens to specify the prognosis of multinodular goiter (MNG) following radiofrequency ablation (RFA), so this study addresses this question for MNG after completely ablating dominant nodules. Methods: The RFA indications for MNG include 2–5 benign nodules with over 50% normal tissue on ultrasound, 1–3 well-defined benign dominant nodules on cytology, largest diameter ≥20 mm and/or with clinical complaints, and patient refusal or unable to undergo surgery. A retrospective study of 185 MNG patients with completely ablated dominant nodules in a single-session RFA was conducted. The efficacy and complications were evaluated at 1, 6, 12 months, and yearly thereafter. Based on retreatment risks, progressive disease (PD), stable disease (SD), and complete relief (CR) were introduced to assess all nodule load changes. PD was clarified as having new/non-target nodules that newly appeared to ACR TI-RADS≥4, or new/enlarged non-target nodules ≥1 cm. Results: The initial ablation ratios of target nodules were 100% at one month. During a mean 22.38 ± 13.75 months (range, 12–60 months), the volume reduction rate of ablated nodules was 98.25% at 24 months without regrowth. Cosmetic and symptomatic scores decreased to 1 and 0, respectively, after 48 months. Of the patients, 9.7% (18/185) had PD and the retreatment rate was 2.2% (4/185). The complication rate was 2.7% (5/185). Conclusion: RFA provides cosmetic and symptomatic relief for an average of two years. RFA is a useful minimally invasive treatment modality for selected MNG patients.

Synthetic aperture radar tomography (TomoSAR) technology effectively mitigates issues such as severe layover in high-resolution synthetic aperture radar (SAR) urban imagery, presenting numerous applications in reconstructing complex 3-D urban scenes. However, prevailing TomoSAR methodologies usually overlook the geometrical feature of the targets, which are particularly pronounced in buildings in urban scenes. To improve the quality of 3-D reconstruction of building targets for large-scale urban scenes, we propose geometric-guided TomoSAR processing in this article. First, the geometrical feature referred to a Z-structure of buildings in TomoSAR point cloud is studied. Then, a Z-structure information extraction approach is proposed to provide prior information for subsequent geometric constraints. Finally, the Z-structure-constraint-based tomographic algorithm is proposed, optimizing the solution space of the original algorithms. Experiments are conducted on real SAR data, and 3-D point clouds of the entire urban scenes are obtained. The proposed algorithm demonstrates commendable performance in point cloud entropy and concentration, especially in the inversion of different floor structures.

All-DC wind power system is one of the important directions of wind power development in the future, and its safe and reliable topology and stable control strategy are the key to the stable operation of the system. In order to solve the problems of poor control flexibility, difficulty of self-starting and low reliability of DC fault crossing in the current all-DC wind farm, this paper presented a topological structure of the parallel all-DC wind power system with turbine-side boost based on a new DC conversion. Based on the dynamic connection mode that each bridge arm of the new DC converter was charged in parallel on the low voltage side and discharged in series on the high voltage side, this paper designed the control strategy of the all-DC wind farm and analysed the operation mode of the all-DC wind farm in the steady state operation stage, the self-starting stage and the DC fault crossing period. Based on PSCAD/EMTDC, the simulation model of the parallel all-DC wind power system with turbine-side boost based on a new DC converter was established. Through the simulation of all-DC wind farm under normal operating conditions, such as steady state and dynamic operation, and fault conditions, such as dynamic cut-in and cut-out of faulty wind turbine and short circuit of DC bus, it was verified that the topology structure of the proposed parallel all-DC wind power system with turbine-side boost based on a new DC converter could improve the control flexibility, reduce the difficulty of self-starting, and ensure the high reliability of DC fault crossing under the premise of feasibility.

Abstract Maintenance tasks in distribution networks are often accompanied by hazards associated with high altitudes and high voltages. By utilising robots instead of human operators to perform these tasks, potential risks can be avoided, while productivity can be increased. This research proposes an intelligent power distribution live‐line operation robot (PDLOR) system based on a stereo camera to replace human to complete work. The PDLOR system consists of several key components, including dual manipulators, wireless tools, a visual perception system, an insulated bucket truck, and a ground control terminal. Once the task is confirmed, the real‐time vision system identification and positioning enable the adjustment of the insulated bucket to position the robot correctly for its intended work. The stereo camera plays a crucial role in accurately recognising and estimating the object's orientation. Additionally, a simplified reconstruction is performed within a virtual simulation environment, which aids in collision detection during path planning. After obtaining the optimal path, it is then communicated to the real manipulator for execution. To validate the feasibility of the PDLOR system, field experiments were conducted in actual distribution network scenarios. The results demonstrate that the PDLOR effectively completes single‐phase power‐line connection tasks within a remarkable 10‐min timeframe.

Compared with the pair-wise registration of point clouds, multi-view point cloud registration is much less studied. In this dissertation, a disordered multi-view point cloud registration method based on the soft trimmed deep network is proposed. In this method, firstly, the expression ability of feature extraction module is improved and the registration accuracy is increased by enhancing feature extraction network with the point pair feature. Secondly, neighborhood and angle similarities are used to measure the consistency of candidate points to surrounding neighborhoods. By combining distance consistency and high dimensional feature consistency, our network introduces the confidence estimation module of registration, so the point cloud trimmed problem can be converted to candidate for the degree of confidence estimation problem, achieving the pair-wise registration of partially overlapping point clouds. Thirdly, the results from pair-wise registration are fed into the model fusion to achieve the rough registration of multi-view point clouds. Finally, the hierarchical clustering is used to iteratively optimize the clustering center model by gradually increasing the number of clustering categories and performing clustering and registration alternately. This method achieves rough point cloud registration quickly in the early stage, improves the accuracy of multi-view point cloud registration in the later stage, and makes full use of global information to achieve robust and accurate multi-view registration without initial value.

Abstract Increased global floating populations is an important driver of local social‐ecological systems change, especially in ecologically fragile areas. However, the limitations of accurate data and specific methods have prevented the exploration of spatial visitation of floating populations and its risk of negative effects on fragile ecosystems. Here, we contribute to filling the knowledge gap in Tibet by adopting large‐scale geolocation data and incorporating factors such as landscape aesthetic value, ecological vulnerability and traffic accessibility. We found that 89.97% of the digital footprints of floating populations in Tibet have entered nature areas with low density of resident population, and 40.57% of them have entered ecologically fragile areas, leading to increased ecological risks. Nature‐based tourism is the main motive for floating populations to enter the ecologically fragile areas, accounting for 65.56%. The central government inadvertently exacerbated ecological risks by leading road construction, resulting in 64.62% of the ecological risks being located in areas with high traffic accessibility. The floating populations entering Tibet have the dual effects of promoting economic development and causing ecological risks. Therefore, it is urgent to put forward strategies to promote the sustainable development in Tibet based on the complex system of “nature‐based tourism–ecological protection–economic income–government behavior”. Read the free Plain Language Summary for this article on the Journal blog.

Investigating the spatiotemporal variation of human activity intensity and its determinants is a crucial basis for further revealing the mechanism of human-environment interaction and optimizing the human development mode. In this study, the human activity intensity on the Qinghai–Tibet Plateau (QTP) from 1990 to 2020 was measured based on the quantitative model of land use data and the actual regional background, and the underlying natural and socioeconomic determinants were investigated using spatial econometric methods. The results demonstrate that (1) the human activity intensity in QTP has increased by 11.96%, and there are differences in different spatial scales; the areas with high human activity intensity are distributed in the Hehuang Valley where Xining City and its surrounding areas are located, as well as the One-River and Two-River Area where Lhasa City and surrounding areas are located. (2) Human activity intensity has significant positive spatial spillover, suggesting that local changes will cause changes in the same direction in adjacent areas. (3) The human activity intensity in QTP is affected by various determinants. Concerning socioeconomic factors, the economic level has no significant impact on the human activity intensity in QTP, which differs from the general regional law. Both urbanization and traffic conditions have a significant positive effect, and the impact intensity continues to increase. Concerning natural factors, topographic relief has a significant positive effect; the impacts of temperature and vegetation coverage have changed from insignificant to a significant positive effect; the impacts of precipitation and river network density have not been verified; there is no linear relationship between altitude and human activity intensity in the entire QTP, while it exists in local regions. Finally, this study proposes three policy implications for the realization of a more harmonious human-environment relationship in QTP.

The effective use of soil biological resources requires a thorough understanding of the ecological roles played by biological communities. The majority of research on soil biological communities has concentrated on their structural aspects, such as diversity and composition. However, further efforts are required to provide a comprehensive understanding of community characteristics. Body size can be used to better understand the ecological activities of soil biological communities, as it is a significant life history feature of organisms. The current study examined alterations to the populations of bacteria, fungi, and nematodes in soil samples that were treated with chemical fertilizer (CF), organic fertilizer (OF), or no fertilizer (CK). The results showed that, in comparison to CK, OF treatments reduced the Shannon diversity of the bacterial community. The fertilization treatments (CF and OF) resulted in a significant increase in the community-weighted mean (CWM) of bacterial body size and the relative abundance of Candidatus koribacter, as compared to the CK treatment. The body size and diversity of the fungal did not significantly differ across the fertilization treatments. Additionally, the CF treatment led to a higher relative abundance of Mortierella in the soil when compared to the CK and OF treatments. The CWM of nematode body size varied dramatically across treatments, whereas there was no discernible variation in diversity or composition. Furthermore, a comprehensive analysis has been carried out utilizing three separate approaches to assess the sensitivity of the soil biological community diversity, composition, and body size to environmental changes. These methods include correlation heatmap, redundancy analysis, and structural equation model. The study consistently showed that the CWM body size of soil organisms is more vulnerable to environmental changes compared to the variety and composition of the community structure. Meanwhile, the current study has revealed that this tendency is less prominent in fungal communities and more apparent in nematode colonies. Our results highlight the importance of body size in characterizing the dynamics of soil biological communities. Our findings imply that when examining the ecological roles of soil biological communities, variations in body size should be taken into account.

IntroductionOur objective in this study was to prepare a novel type of polymethyl methacrylate (PMMA) bone cement, analyze its material properties, and evaluate its safety and antibacterial efficacy.MethodsA halamine compound methacrylate antibacterial PMMA bone cement containing an N-Cl bond structure was formulated, and its material characterization was determined with Fourier transform infrared spectroscopy (FT-IR) and 1H-NMR. The antibacterial properties of the material were studied using contact bacteriostasis and releasing-type bacteriostasis experiments. Finally, in vitro and in vivo biocompatibility experiments were performed to analyze the toxic effects of the material on mice and embryonic osteoblast precursor cells (MC3T3-E1).ResultsIncorporation of the antibacterial methacrylate monomer with the N-halamine compound in the new antibacterial PMMA bone cement significantly increased its contact and releasing-type bacteriostatic performance against Staphylococcus aureus. Notably, at 20% and 25% additions of N-halamine compound, the contact and releasing-type bacteriostasis rates of bone cement samples reached 100% (p < 0.001). Furthermore, the new antibacterial bone cement containing 5%, 10%, and 15% N-halamine compounds showed good biocompatibility in vitro and in vivo.ConclusionIn this study, we found that the novel antibacterial PMMA bone cement with N-halamine compound methacrylate demonstrated good contact and releasing-type bacteriostatic properties against S. aureus. In particular, bone cement containing a 15% N-halamine monomer exhibited strong antibacterial properties and good in vitro and in vivo biocompatibility.

Chondroitin sulfate (CS) is a sulfated linear polysaccharide with different functional activities, including antioxidant, anti-inflammatory, lipid-lowering, and immune regulation. As natural sulfated polysaccharides have high molecular weight, high apparent viscosity, low water solubility, complex structure, and high negative charge, they have difficulty binding to receptors within cells across tissue barriers, resulting in low bioavailability and unclear structure–activity relationships. In this study, an H2O2-Vc oxidative degradation system was employed to perform environmentally friendly and controllable degradation of CS extracted from the nasal cartilage of Shaanxi Yellow cattle. Two low-molecular-weight chondroitin sulfates (LMWCSs), CS-1 (14.8 kDa) and CS-2 (50.9 kDa), that exhibit strong in vitro free radical scavenging ability were obtained, and their structures were characterized. Mice intraperitoneally administered lipopolysaccharide (LPS) were used to explore the cognitive intervention effects of LMWCS. Supplementing CS-1 and CS-2 significantly downregulated the levels of the serum inflammatory factors, TNF-α and IL-1β, promoted the expression of GSH in the brain, and inhibited the production of the lipid peroxidation product, malondialdehyde (MDA), ultimately inhibiting LPS-induced cognitive impairment in mice. Surprisingly, compared to the LPS model group, the abundances of Streptococcus, Eisenbergiella, Vampirovibrio, Coprococcus, Enterococcus and Lachnoanaerobaculum were significantly increased in the intestines of mice in the CS-1 and CS-2 group, whereas those of Parabacteroides and Mycoplasma were significantly decreased. Altogether, this study provides a theoretical basis for the comprehensive utilization of agricultural and animal resources and the application of brain nutrition, anti-inflammatory, and LMWCS health products.

Objective: To evaluate the effectiveness of different acupuncture treatments for mammary gland hyperplasia (MGH) using a network meta-analysis. Methods: Several databases were searched without language restrictions from 2000 to February 2023, including PubMed, Embase, Web of Science, Cochrane Library, China Science and Technology Journal Database, China Biology Medicine Database, Wanfang Database, China National Knowledge Infrastructure Database, and other professional websites and gray literature. Inclusion criteria were adult women diagnosed with MGH; intervention measures included acupuncture and related therapies; the control group was treated with simple drugs; and the research type was a randomized controlled trial (RCT). The primary outcomes were treatment effectiveness and estradiol and progesterone levels. Secondary outcomes were breast lump size and visual analog scale (VAS) score of breast pain. Exclusion criteria were studies unrelated to MGH, incorrect study populations, control measures or interventions, incomplete data, non-RCTs, case reports, and animal experiments. Cochrane tools were used to assess the risk of bias. The R software (x64 version 4.2.1), Review Manager 5.3 software and STATA 16.0 software were used for data analysis. Results: Following a rigorous screening process, data extraction, and quality assessment, 48 eligible RCTs encompassing 4,500 patients with MGH and 16 interventions were included. The results indicated that acupuncture, alone or in combination with traditional Chinese or Western medicine, had better therapeutic effects than conventional therapy. In terms of effectiveness, warm needle acupuncture was the best choice (94.6%). Bloodletting pricking was the most effective method (85.7%) for lowering progesterone levels. Bloodletting pricking was the most effective method (98.3%) for lowering estradiol levels. Manual acupuncture combined with traditional Chinese medicine was the most effective (74.5%) treatment to improve the size of the breast lump. Warm needle acupuncture was the most effective (69.8%) in improving the VAS score. Conclusion: Acupuncture therapy was more effective in treating MGH than drug therapy alone, and warm needle acupuncture and bloodletting pricking were the two best options. However, larger sample sizes and high-quality RCTs are required.

This study aimed to evaluate the protective role and potential mechanisms of Xie Zhuo Tiao Zhi decoction (XZTZ) on alcohol-associated liver disease (ALD). XZTZ significantly alleviated alcohol-induced liver dysfunction, based on histological examinations and biochemical parameters after 4-week administration. Mechanically, alcohol-stimulated hepatic oxidative stress was ameliorated by XZTZ, accompanied by the improvement of Nrf2/Keap1 expression and alcohol-activated phosphorylation of pro-inflammatory transcription factors, including JNK, P38, P65, and IκBα, were rescued by XZTZ. In conclusion, XZTZ demonstrates potential in alleviating alcohol-induced liver injury, oxidative stress, and inflammation possibly through modulation of Nrf2/Keap1 and MAPKs/NF-κB signaling pathways, suggesting its potential as a therapeutic option for patients with alcoholic liver disease.

Coronary heart disease (CHD) is a leading cause of mortality globally and poses a significant threat to public health. Coronary angiography (CAG) is a gold standard for the clinical diagnosis of CHD, but its invasiveness restricts its widespread application. In this study, we utilized a pulse diagnostic device equipped with pressure and photoelectric sensors to synchronously and non-invasively capture wrist pressure pulse waves and fingertip photoplethysmography (FPPG) of patients undergoing CAG. The extracted features were utilized in constructing random forest-based models to assessing the severity of coronary artery lesions. Notably, Model 3, incorporating both wrist pulse and FPPG features, surpassed Model 1 (solely utilizing wrist pulse features) and Model 2 (solely utilizing FPPG features). Model3 achieved an Accuracy, Precision, Recall, and F1-score of 78.79%, 78.69%, 78.79%, and 78.70%, respectively. Compared to Model1 and Model2, Model 3 exhibited improvements by 4.55%, 5.25%, 4.55%, and 5.12%, and 6.06%, 6.58%, 6.06%, and 6.54% respectively. This fusion of wrist pulse and FPPG features in Model 3 highlights the advantages of multi-source information fusion for model optimization. Additionally, this research provides invaluable insights into the novel development of diagnostic devices imbued with TCM principles and their potential in managing cardiovascular diseases.

In the present study, small RNA (sRNA) data from Ascosphaera apis were filtered from sRNA-seq datasets from the gut tissues of A. apis-infected Apis mellifera ligustica worker larvae, which were combined with the previously gained sRNA-seq data from A. apis spores to screen differentially expressed milRNAs (DEmilRNAs), followed by trend analysis and investigation of the DEmilRNAs in relation to significant trends. Additionally, the interactions between the DEmilRNAs and their target mRNAs were verified using a dual-luciferase reporter assay. In total, 974 A. apis milRNAs were identified. The first base of these milRNAs was biased toward U. The expression of six milRNAs was confirmed by stem–loop RT-PCR, and the sequences of milR-3245-y and milR-10285-y were validated using Sanger sequencing. These miRNAs grouped into four significant trends, with the target mRNAs of DEmilRNAs involving 42 GO terms and 120 KEGG pathways, such as the fungal-type cell wall and biosynthesis of secondary metabolites. Further investigation demonstrated that 299 DEmilRNAs (novel-m0011-3p, milR-10048-y, bantam-y, etc.) potentially targeted nine genes encoding secondary metabolite-associated enzymes, while 258 (milR-25-y, milR-14-y, milR-932-x, etc.) and 419 (milR-4561-y, milR-10125-y, let-7-x, etc.) DEmilRNAs putatively targeted virulence factor-encoded genes and nine genes involved in the MAPK signaling pathway, respectively. Additionally, the interaction between ADM-B and milR-6882-x, as well as between PKIA and milR-7009-x were verified. Together, these results not only offer a basis for clarifying the mechanisms underlying DEmilRNA-regulated pathogenesis of A. apis and a novel insight into the interaction between A. apis and honey bee larvae, but also provide candidate DEmilRNA–gene axis for further investigation.

This study investigated the effects of defective pear fermentation (DPF) diets on growth performance and gastrointestinal microbial communities in 60 healthy male small-tailed Han sheep, aged 90 days. The sheep were randomly divided into four groups, each consisting of three replicates with five sheep per replicate. Initially, all groups received a basal diet for seven days during the adaptation stage. Subsequently, for 60 days, group C (control) was fed a basal diet, group X received a basal diet with 2% DPF, group Y had a basal diet with 4% DPF, and group Z was fed a basal diet with 6% DPF. The results indicated that group Y experienced a significant increase in average daily gain (ADG) and average daily feed intake (ADFI). The addition of DPF significantly elevated the levels of GSH-Px and notably reduced MDA content compared to group C. Analysis of gastrointestinal microbiota showed that groups receiving DPF had increased relative abundances of Lachnospiraceae_NK3A20_group, norank_f p-2534-18B5_gut_group, Acetitomaculum, Actinobacteriota, Bacteroidota and Ruminococcus_gauvreauii_group, and decreased abundances of Proteobacteria, Prevotella, Staphylococcus, and Psychrobacter compared to group C. Group X exhibited the highest relative abundance of Olsenella, while group Y showed a significant increase in unclassified_f Lachnospiraceae compared to the other groups. Bacterial function prediction indicated that pathways related to energy metabolism were more prevalent in group X and Y. This study preliminarily confirms the feasibility of using DPF as feed additives, providing a foundation for further research and evaluation of DPF's application in animal production.

In 2020, bladder cancer, which commonly presents as urothelial carcinoma, became the 10th most common malignancy. For patients with metastatic urothelial carcinoma, the standard first-line treatment remains platinum-based chemotherapy, with immunotherapy serving as an alternative in cases of programmed death ligand 1 expression. However, treatment options become limited upon resistance to platinum and programmed death 1 or programmed death ligand 1 agents. Since the FDA’s approval of Enfortumab Vedotin and Sacituzumab Govitecan, the therapeutic landscape has expanded, heralding a shift towards antibody–drug conjugates as potential first-line therapies. Our review employed a robust scientometric approach to assess 475 publications on antibody–drug conjugates in urothelial carcinoma, revealing a surge in related studies since 2018, predominantly led by U.S. institutions. Moreover, 89 clinical trials were examined, with 36 in Phase II and 13 in Phase III, exploring antibody–drug conjugates as both monotherapies and in combination with other agents. Promisingly, novel targets like HER-2 and EpCAM exhibit substantial therapeutic potential. These findings affirm the increasing significance of antibody–drug conjugates in urothelial carcinoma treatment, transitioning them from posterior-line to frontline therapies. Future research is poised to focus on new therapeutic targets, combination therapy optimization, treatment personalization, exploration of double antibody-coupled drugs, and strategies to overcome drug resistance.

Background: The increasing prevalence of hepatic steatosis presents a considerable challenge to public health. There is a critical need for the development of novel preventive and screening strategies for this condition. This study evaluated the potential applications of wrist pulse detection technology for the early detection of liver diseases. The pulse time-domain features of a medical exam population with and without hepatic steatosis were assessed to develop a screening model for this disease. Methods: Participants were consecutively recruited from March 2021 to March 2022 in the medical examination centers of the Yueyang Hospital of Integrated Traditional Chinese and Western Medicine and the Shanghai Municipal Hospital of Traditional Chinese Medicine. Clinical data from 255 participants, including general information (sex, age, and body mass index), and data related to glucose and blood lipids (fasting plasma glucose, triglyceride, total cholesterol, high-density lipoprotein, and low-density lipoprotein levels) were collected. Wrist pulse signals were acquired using a pulse detection device, and the pulse time-domain features, including t1, t4, t5, T, w1, w2, h2/h1, h3/h1, and h5/h1 were extracted. Participants were assigned to hepatic steatosis and non-hepatic steatosis groups according to their abdominal ultrasound examination results. Their clinical data and pulse time-domain features were compared using chi-square and parametric or non-parametric statistical methods. Three datasets were used to construct screening models for hepatic steatosis based on the random forest algorithm. The datasets for modeling were defined as Dataset 1, containing blood glucose and lipid data and general information; Dataset 2, containing time-domain features and general information; Dataset 3, containing time-domain features, blood glucose and lipid data, and general information. The evaluation metrics, accuracy, precision, recall, F1-score, and areas under the receiver operating characteristic curve (AUC) were compared for each model. Results: The time-domain features of the two groups differed significantly. The t1, t4, t5, T, h2/h1, h3/h1, w1, and w2 features were higher in the hepatic steatosis group than in the non-hepatic steatosis group (P < 0.05), while the h5/h1 features were lower in the hepatic steatosis group than in the non-hepatic steatosis group (P < 0.05). The screening models for hepatic steatosis based on both time-domain features and blood glucose and lipid data outperformed those based on time-domain features or blood markers alone. The accuracy, precision, recall, F1-score, and AUC of the combined model were 81.18%, 80.56%, 76.32%, 79%, and 87.79%, respectively. These proportions were 1.57%, 1.86%, 1.76%, 2%, and 3.54% higher, respectively, than those of the model based on time-domain features alone and 3.14%, 4.2%, 2.64%, 4%, and 6.47% higher, respectively, than those of the model based on blood glucose and lipid alone. Conclusion: The early screening model for hepatic steatosis using datasets that included pulse time-domain features achieved better performance. The findings suggest that pulse detection technology could be used to inform the development of a mobile medical device or remote home monitoring system to test for hepatitis steatosis.