Search

The integrated and indivisible nature of the SDGs is facing implementation challenges due to the silo approaches. We present the three interconnected foci (SDG interactions, modeling, and tools) at the science-policy interface to address these challenges. Accounting for them will support accelerated SDG progress, operationalizing the integration and indivisibility principles.

The second-to-fourth digit (2D:4D) ratio is thought to be associated with prenatal androgen exposure. However, the relationship between the 2D:4D ratio and hypospadias is poorly understood, and its molecular mechanism is not clear. In this study, by analyzing the hand digit length of 142 boys with hypospadias (23 distal, 68 middle, and 51 proximal) and 196 controls enrolled in Shanghai Children’s Hospital (Shanghai, China) from December 2020 to December 2021, we found that the 2D:4D ratio was significantly increased in boys with hypospadias (P < 0.001) and it was positively correlated with the severity of the hypospadias. This was further verified by the comparison of control mice and prenatal low testosterone mice model obtained by knocking out the risk gene (dynein axonemal heavy chain 8 [DNAH8]) associated with hypospadias. Furthermore, the discrepancy was mainly caused by a shift in 4D. Proteomic characterization of a mouse model validated that low testosterone levels during pregnancy can impair the growth and development of 4D. Comprehensive mechanistic explorations revealed that during the androgen-sensitive window, the downregulation of the androgen receptor (AR) caused by low testosterone levels, as well as the suppressed expression of chondrocyte proliferation-related genes such as Wnt family member 5a (Wnt5a), Wnt5b, Smad family member 2 (Smad2), and Smad3; mitochondrial function-related genes in cartilage such as AMP-activated protein kinase (AMPK) and nuclear respiratory factor 1 (Nrf-1); and vascular development-related genes such as myosin light chain (MLC), notch receptor 3 (Notch3), and sphingosine kinase 1 (Sphk1), are responsible for the limitation of 4D growth, which results in a higher 2D:4D ratio in boys with hypospadias via decreased endochondral ossification. This study indicates that the ratio of 2D:4D is a risk marker of hypospadias and provides a potential molecular mechanism.

In situ-forming hydrogels are an attractive option for corneal regeneration, and the delivery of growth factors from such constructs have the potential to improve re-epithelialization and stromal remodeling. However, challenges persist in controlling the release of therapeutic molecules from hydrogels. Here, an in situ-forming bio-orthogonally crosslinked hydrogel containing growth factors tethered via photocleavable linkages (PC-HACol hydrogel) was developed to accelerate corneal regeneration. Epidermal growth factor (EGF) was conjugated to the hydrogel backbone through photo-cleavable (PC) spacer arms and was released when exposed to mild intensity ultraviolet (UV) light (2–5 mW/cm2, 365 nm). The PC-HACol hydrogel rapidly gelled within a few minutes when applied to corneal defects, with excellent transparency and biocompatibility. After subsequent exposure to UV irradiation, the hydrogel promoted the proliferation and migration of corneal epithelial cells in vitro. The rate of re-epithelialization was positively correlated to the frequency of irradiation, verified through ex vivo rabbit cornea organ culture studies. In an in vivo rat corneal wound healing study, the PC-HACol hydrogel exposed to UV light significantly promoted re-epithelialization, the remodeling of stromal layers, and exhibited significant anti-scarring effects, with minimal α-SMA and robust ALDH3A1 expression. Normal differentiation of the regenerated epithelia after healing was evaluated by expression of the corneal epithelial biomarker, CK12. The remodeled cornea exhibited full recovery of corneal thickness and layer number without hyperplasia of the epithelium.

Sinamma Lin & Li, 2014 is a small tetrablemmid genus distributed in China, with three currently known species: Sinamma oxycera Lin & Li, 2014 from Guangxi Zhuang Autonomous Region and S. quadrata Tong & Li, 2022 and S. yingae Tong & Li, 2022 from Guangdong Province.While examining spider specimens obtained by sifting leaf litter from Danxiashan National Nature Reserve in Guangdong Province of China, we discovered a new species of the genus Sinamma, S. danxia sp. nov., which is described here.

The nutritional quality and safety of fruit and vegetable products are the urgent problems and research hotspots in the processing field. High-pressure homogenization, a non-thermal processing technology, can maximize the preservation of the nutritional quality, color and flavor of fruit and vegetable products while sterilizing and inactivating enzymes, and is expected to replace thermal processing technology. This article reviews the effects of high-pressure homogenization on the color, stability and nutritional components of fruit and vegetable products, and summarizes the killing effect and mechanism of high-pressure homogenization on microorganisms. It discusses the prospects and challenges of high-pressure homogenization technology in the application of fruit and vegetable products from two aspectsof equipment and technology, providing a theoretical reference for the innovation of high-pressure homogenization technology and equipment.

Abstract Background Delirium, marked by acute cognitive decline, poses a life-threatening issue among older individuals, especially after cardiac surgery, with prevalence ranging from 15 to 80%. Postoperative delirium is linked to increased morbidity and mortality. Although clinical trials suggest preventability, there is limited research on intranasal insulin (INI) for cardiac surgery-related delirium. INI has shown promise in managing cognitive disorders. It rapidly elevates brain hormone levels, enhancing memory even in non-impaired individuals. While effective in preventing delirium in gastrointestinal surgery, its impact after cardiac surgery remains understudied, especially for middle-aged patients. Method This is a prospective randomized, double-blind, single-center controlled trial. A total of 76 eligible participants scheduled for elective on-pump cardiac surgery will be enrolled and randomly assigned in a 1:1 ratio to either receive Intranasally administered insulin (INI) or intranasally administered normal saline. The primary outcome of our study is the incidence of postoperative delirium (POD). Secondary outcomes include duration of ICU, postoperative hospital length of stay, all in-hospital mortality, the change in MMSE scores pre- and post-operation, and incidence of postoperative cognitive dysfunction at 1 month, 3 months, and 6 months after operation. Moreover, we will subjectively and objectively evaluate perioperative sleep quality to investigate the potential impact of nasal insulin on the development of delirium by influencing sleep regulation. Discussion Our study will aim to assess the impact of intranasal administration of insulin on the incidence of postoperative delirium in middle-aged patients undergoing on-pump elective cardiac surgery. If intranasal insulin proves to be more effective, it may be considered as a viable alternative for preventing postoperative delirium. Trial registration ChiCTR ChiCTR2400081444. Registered on March 1, 2024.

Abstract Background The interleukin-1 receptor accessory protein (IL1RAP) is highly expressed on acute myeloid leukemia (AML) bulk blasts and leukemic stem cells (LSCs), but not on normal hematopoietic stem cells (HSCs), providing an opportunity to target and eliminate the disease, while sparing normal hematopoiesis. Herein, we report the activity of BIF002, a novel anti-IL1RAP/CD3 T cell engager (TCE) in AML. Methods Antibodies to IL1RAP were isolated from CD138+ B cells collected from the immunized mice by optoelectric positioning and single cell sequencing. Individual mouse monoclonal antibodies (mAbs) were produced and characterized, from which we generated BIF002, an anti-human IL1RAP/CD3 TCE using Fab arm exchange. Mutations in human IgG1 Fc were introduced to reduce FcγR binding. The antileukemic activity of BIF002 was characterized in vitro and in vivo using multiple cell lines and patient derived AML samples. Results IL1RAP was found to be highly expressed on most human AML cell lines and primary blasts, including CD34+ LSC-enriched subpopulation from patients with both de novo and relapsed/refractory (R/R) leukemia, but not on normal HSCs. In co-culture of T cells from healthy donors and IL1RAPhigh AML cell lines and primary blasts, BIF002 induced dose- and effector-to-target (E:T) ratio-dependent T cell activation and leukemic cell lysis at subnanomolar concentrations. BIF002 administered intravenously along with human T cells led to depletion of leukemic cells, and significantly prolonged survival of IL1RAPhigh MOLM13 or AML patient-derived xenografts with no off-target side effects, compared to controls. Of note, BiF002 effectively redirects T cells to eliminate LSCs, as evidenced by the absence of disease initiation in secondary recipients of bone marrow (BM) from BIF002+T cells-treated donors (median survival not reached; all survived > 200 days) compared with recipients of BM from vehicle- (median survival: 26 days; p = 0.0004) or isotype control antibody+T cells-treated donors (26 days; p = 0.0002). Conclusions The novel anti-IL1RAP/CD3 TCE, BIF002, eradicates LSCs and significantly prolongs survival of AML xenografts, representing a promising, novel treatment for AML.

Abstract The maintenance of hematopoietic stem cell (HSC) functional integrity is essential for effective hematopoietic regeneration when suffering from injuries. Studies have shown that the innate immune pathways play crucial roles in the stress response of HSCs, whereas how to precisely modulate these pathways is not well characterized. Here, we identify the E3 ubiquitin ligase tripartite motif-containing 47 (Trim47) as a negative regulator of the mitochondrial antiviral-signaling protein (MAVS)-mediated innate immune pathway in HSCs. We find that Trim47 is predominantly enriched in HSCs, and its deficiency impairs the function and survival of HSCs after exposure to 5-flurouracil (5-FU) and irradiation (IR). Mechanistically, Trim47 impedes the excessive activation of the innate immune signaling and inflammatory response via K48-linked ubiquitination and degradation of MAVS. Collectively, our findings demonstrate a role of Trim47 in preventing stress-induced hematopoietic failure and thus provide a promising avenue for treatment of related diseases in the clinic.

Jatropha curcas L. (J. curcas), a shrub plant of the Euphorbiaceae family, has received enormous attention as a promising biofuel plant for the production of biodiesel and medical potential in ethnopharmacology. However, the tumor-promoter toxin phorbol esters present in J. curcas raise concerns for health and environmental risk as its large-scale cultivation limits the use of meal obtained after oil extraction for animal feed. Here, we determined the variation of phorbol ester profiles and contents in eight J. curcas tissues by high-performance liquid chromatography (HPLC) and found phorbol esters present in all parts of the plant except the seed shell. We showed tissue-specific patterns of accumulation of phorbol esters and associated terpenoids at the transcriptional level with high transcript levels in reproductive and young tissues. Genes involved in the same module of terpenoids biosynthesis were positively correlated. We further present diverse abiotic and biotic stresses that had different effects on the accumulation of transcripts in terpenoids shared and branched terpenoid pathways in plant seedlings. The fine-tuning of terpenoids biosynthesis may link with ecological functions in plants under extreme environments and defense against pathogens.

【Objective】The study was carried out to explore the distribution patterns of rhizospheric microbial communities in different resistant pepper varieties, aiming to provide a basis for the targeted optimization of rhizospheric microbial community structure of pepper.【Method】Taking the susceptible pepper variety 'Hailan 99' (HL99) and the resistant variety 'Sanxiaqing' (SSQ) as experimental materials, high-throughput sequencing technology was employed to analyze and compare the effects of susceptible and non-susceptible soil environments on the community diversity, species composition, correlation networks and function of bacteria and fungi in the rhizosphere soil of different disease-resistant pepper plants.【Result】Through high-throughput sequencing, a total of 66 617 operational taxonomic units (OTUs) from soil bacterial samples were obtained, among which the dominant phyla were Proteobacteria and Bacteroidetes, with the relative abundances of approximately 40.1% and 15.3%, respectively. From soil fungal samples, 2 948 OTUs were obtained, among which the dominant phylum was Ascomycota, with an average relative abundance of approximately 47.8%. The rhizospheric microbial community structure and species composition of pepper varieties showed significant differences under different soil conditions. Under susceptible soil conditions, the diversity of bacterial communities in pepper rhizosphere decreased, while the diversity of fungal communities increased. The bacterial OTUs decreased by 6.5%-7.8%, and fungal OTUs increased by 8.8%-9.8%. The relative abundance of Fusarium fungi was significantly higher in the susceptible group (5.0%) compared with that in the resistant group (4.8%), while the relative abundance of beneficial fungi like Mortierella and Trichoderma and beneficial bacteria like Pseudomonas and Bacillus was significantly lower in the susceptible group than that in the resistant group. Overall, under the susceptible soil conditions, the abundance of beneficial rhizosphere fungi and bacteria in the resistant group was higher than that in the susceptible group, contributing to a better soil micro-ecological environment. Based on species abundance tables, the correlation relationships of fungi-fungi, fungi-bacteria and bacteria-bacteria species were calculated respectively at the genus level. The results indicated that the rhizosphere microorganisms of pepper formed a complex ecological network, with high co-occurrence between fungi-fungi and fungi-bacteria (with a positive correlation percentage higher than 50%), suggesting that cooperative relationships outweighed competitive ones. The bacteria-bacteria network structure was more complex, with a positive correlation percentage of about 49.9%.【Conclusion】The rhizospheric microbial community structures of different resistant varieties exhibit significant differences under different soil conditions. The interaction of rhizosphere microorganisms forms a complex microbial ecological network structure. The relative abundance of beneficial fungi and bacteria is higher in the resistant variety than that in the susceptible variety, which suppresses more pathogenic microbes, leading to a healthier soil micro-ecological environment. The key groups identified in this study, including Fusarium, Verticillium, Trichoderma, Bacillus and Pseudomonas, will provide important information for the targeted optimization of rhizospheric microbial community structures and offer crucial theoretical references for the biological control of soil-borne diseases.

Abstract The development of cathode materials with controllable physicochemical structures and explicit catalytic sites is important in rechargeable Zn–air batteries (ZABs). Covalent organic frameworks (COFs) have garnered increasing attention owing to their facile synthesis methods, ordered pore structure, and selectivity of functional groups. However, the sluggish kinetics of oxygen evolution reaction (OER) or oxygen reduction reaction (ORR) inhibit their practical applications in ZABs. Herein, nucleophilic substitution is adopted to synthesize pyridine bi‐triazine covalent organic framework (denoted as O‐COF), and meanwhile, ionothermal conversion synthesis is employed to load MOx (M=Fe, Co) onto carbon nanosheet (named as FeCo@NC) to modulate the electronic structure. The Fe, Co‐N codoped carbon material possesses a large portion of pyridinic N and M‐N, high graphitization, and a larger BET surface area. An outstanding bifunctional activity has been exhibited in FeCo@NC, which provides a small voltage at 10 mA cm−2 for OER (E10 = 1.67 V) and a remarkable half‐wave voltage for ORR (E1/2 = 0.86 V). More impressively, when assembling ZABs, it displays notable rate performance, significant specific capacity (783.9 mAh gZn−1), and satisfactory long‐term endurance. This method of regulating covalent organic framework and ionothermal synthesis can be extended to design diverse catalysts.

Abstract The analysis of genomic variations in offspring after implantation has been infrequently studied. In this study, we aim to investigate the extent of de novo mutations in humans from developing fetus to birth. Using high-depth whole-genome sequencing, 443 parent-offspring trios were studied to compare the results of de novo mutations (DNMs) between different groups. The focus was on fetuses and newborns, with DNA samples obtained from the families’ blood and the aspirated embryonic tissues subjected to deep sequencing. It was observed that the average number of total DNMs in the newborns group was 56.26 (54.17–58.35), which appeared to be lower than that the multifetal reduction group, which was 76.05 (69.70–82.40) (F = 2.42, P = 0.12). However, after adjusting for parental age and maternal pre-pregnancy body mass index (BMI), significant differences were found between the two groups. The analysis was further divided into single nucleotide variants (SNVs) and insertion/deletion of a small number of bases (indels), and it was discovered that the average number of de novo SNVs associated with the multifetal reduction group and the newborn group was 49.89 (45.59–54.20) and 51.09 (49.22–52.96), respectively. No significant differences were noted between the groups (F = 1.01, P = 0.32). However, a significant difference was observed for de novo indels, with a higher average number found in the multifetal reduction group compared to the newborn group (F = 194.17, P

Abstract Background Compared to traditional thoracotomy, transapical transcatheter aortic valve implantation (TAVI) surgery offers reduced trauma and faster recovery, fostering the adoption of enhanced recovery after surgery (ERAS) protocols in cardiac surgery. Despite these advancements, postoperative pain management has received insufficient attention. The potential effects of multi-mode analgesia, including ultrasound-guided serratus anterior plane block (SAPB), on postoperative pain and early quality of recovery have not been widely studied, lacking comprehensive prospective evidence. Therefore, this study aims to investigate the impact of SAPB combined with general anesthesia on early recovery quality and analgesic efficacy in transapical TAVI patients. Methods This prospective, randomized controlled study will enroll 70 patients undergoing transapical TAVI, randomly allocated to either the SAPB group or the control group. The primary outcome, assessed using Quality of Recovery-40 (QOR-40) scale, focuses on the quality of recovery at 24 h and 48 h postoperatively. Secondary outcomes include the visual analog scale (VAS) pain scores at rest and during coughing at 6 h, 12 h, 24 h, and 48 h after surgery, frequency of patient-controlled analgesia (PCA) utilization at 24 h and 48 h, opioid consumption at 24 h and 48 h, time and frequency of rescue analgesia and severe pain at 24 h and 48 h, incidence of nausea and vomiting at 48 h after surgery, and dosage of antiemetic drugs. Discussion The purpose of our study is to evaluate the effects of ultrasound-guided SAPB combined with general anesthesia on postoperative early quality of recovery and analgesia in transapical TAVI patients. The results obtained may provide valuable insight for the implementation of multi-mode analgesia and enhanced ERAS in this specific patient population. Trial registration China Clinical Trial Register ChiCTR2300068584. Registered on 24 February 2023.

Abstract Background Off-pump coronary artery bypass grafting (OPCABG) presents distinct hemodynamic characteristics, yet the relationship between intraoperative hypotension and short-term adverse outcomes remains clear. Our study aims to investigate association between intraoperative hypotension and postoperative acute kidney injury (AKI), mortality and length of stay in OPCABG patients. Methods Retrospective data of 494 patients underwent OPCABG from January 2016 to July 2023 were collected. We analyzed the relationship between intraoperative various hypotension absolute values (MAP > 75, 65 65 mmHg emerges as a significant independent protective factor for AKI in OPCABG and IOH is related to length of hospital stay. Proactive intervention targeting intraoperative hypotension may provide a potential opportunity to reduce postoperative renal injury and hospital stay. Trial registration ChiCTR2400082518. Registered 31 March 2024. https://www.chictr.org.cn/bin/project/edit?pid=225349 .

Abstract Background Ocular tuberculosis is a relatively rare extrapulmonary manifestation of tuberculosis. This vision-threatening disease is extremely challenging to diagnose, particularly because it can mimic other diseases. We report a case of tuberculous ciliary body granuloma initially diagnosed as bullous retinal detachment. Case report A 52-year-old female presented with bullous retinal detachment in her left eye, and ultrasound biomicroscopy (UBM) verified the presence of a lesion with ciliary body granulomatous inflammation. The T-SPOT was positive, and the purified protein derivative (PPD) test was strongly positive (diameter of 20 mm). Following the administration of oral anti-tuberculosis regimen combined with prednisone, the retina gradually became reattached, the ciliary body granuloma became significantly reduced in size, and the visual acuity of the patient noticeably improved. Conclusions Tuberculous ciliary body granulomas can cause bullous exudative retinal detachment and can be diagnosed with UBM. Early and full-course anti-tuberculosis treatment (ATT) combined with corticosteroid therapy can improve the patient prognosis.

Abstract Variants in potassium channel‐related genes are one of the most important mechanisms underlying abnormal neuronal excitation and disturbances in the cellular resting membrane potential. These variants can cause different forms of epilepsy, which can seriously affect the physical and mental health of patients, especially those with refractory epilepsy or status epilepticus, which are common among pediatric patients and are potentially life‐threatening. Variants in potassium ion channel‐related genes have been reported in few studies; however, to our knowledge, no systematic review has been published. This study aimed to summarize the epilepsy phenotypes, functional studies, and pharmacological advances associated with different potassium channel gene variants to assist clinical practitioners and drug development teams to develop evidence‐based medicine and guide research strategies. PubMed and Google Scholar were searched for relevant literature on potassium channel‐related epilepsy reported in the past 5–10 years. Various common potassium ion channel gene variants can lead to heterogeneous epilepsy phenotypes, and functional effects can result from gene deletions and compound effects. Administration of select anti‐seizure medications is the primary treatment for this type of epilepsy. Most patients are refractory to anti‐seizure medications, and some novel anti‐seizure medications have been found to improve seizures. Use of targeted drugs to correct aberrant channel function based on the type of potassium channel gene variant can be used as an evidence‐based pathway to achieve precise and individualized treatment for children with epilepsy. Plain Language Summary In this article, the pathogenesis and clinical characteristics of epilepsy caused by different types of potassium channel gene variants are reviewed in the light of the latest research literature at home and abroad, with the expectation of providing a certain theoretical basis for the diagnosis and treatment of children with this type of disease.

Abstract Objective To develop an AI-assisted MRI model to identify surgical target areas in pediatric hip and periarticular infections. Methods A retrospective study was conducted on the pediatric patients with hip and periarticular infections who underwent Magnetic Resonance Imaging(MRI)examinations from January 2010 to January 2023 in three hospitals in China. A total of 7970 axial Short Tau Inversion Recovery (STIR) images were selected, and the corresponding regions of osteomyelitis (label 1) and abscess (label 2) were labeled using the Labelme software. The images were randomly divided into training group, validation group, and test group at a ratio of 7:2:1. A Mask R-CNN model was constructed and optimized, and the performance of identifying label 1 and label 2 was evaluated using receiver operating characteristic (ROC) curves. Calculation of the average time it took for the model and specialists to process an image in the test group. Comparison of the accuracy of the model in the interpretation of MRI images with four orthopaedic surgeons, with statistical significance set at P

Abstract Background Hematopoietic stem cell (HSC) regeneration underlies hematopoietic recovery from myelosuppression, which is a life-threatening side effect of cytotoxicity. HSC niche is profoundly disrupted after myelosuppressive injury, while if and how the niche is reshaped and regulates HSC regeneration are poorly understood. Methods A mouse model of radiation injury-induced myelosuppression was built by exposing mice to a sublethal dose of ionizing radiation. The dynamic changes in the number, distribution and functionality of HSCs and megakaryocytes were determined by flow cytometry, immunofluorescence, colony assay and bone marrow transplantation, in combination with transcriptomic analysis. The communication between HSCs and megakaryocytes was determined using a coculture system and adoptive transfer. The signaling mechanism was investigated both in vivo and in vitro, and was consolidated using megakaryocyte-specific knockout mice and transgenic mice. Results Megakaryocytes become a predominant component of HSC niche and localize closer to HSCs after radiation injury. Meanwhile, transient insulin-like growth factor 1 (IGF1) hypersecretion is predominantly provoked in megakaryocytes after radiation injury, whereas HSCs regenerate paralleling megakaryocytic IGF1 hypersecretion. Mechanistically, HSCs are particularly susceptible to megakaryocytic IGF1 hypersecretion, and mTOR downstream of IGF1 signaling not only promotes activation including proliferation and mitochondrial oxidative metabolism of HSCs, but also inhibits ferritinophagy to restrict HSC ferroptosis. Consequently, the delicate coordination between proliferation, mitochondrial oxidative metabolism and ferroptosis ensures functional HSC expansion after radiation injury. Importantly, punctual IGF1 administration simultaneously promotes HSC regeneration and hematopoietic recovery after radiation injury, representing a superior therapeutic approach for myelosuppression. Conclusions Our study identifies megakaryocytes as a last line of defense against myelosuppressive injury and megakaryocytic IGF1 as a novel niche signal safeguarding HSC regeneration.

Abstract Transcriptome-wide association study (TWAS) is a popular approach to dissect the functional consequence of disease associated non-coding variants. Most existing TWAS use bulk tissues and may not have the resolution to reveal cell-type specific target genes. Single-cell expression quantitative trait loci (sc-eQTL) datasets are emerging. The largest bulk- and sc-eQTL datasets are most conveniently available as summary statistics, but have not been broadly utilized in TWAS. Here, we present a new method EXPRESSO (EXpression PREdiction with Summary Statistics Only), to analyze sc-eQTL summary statistics, which also integrates 3D genomic data and epigenomic annotation to prioritize causal variants. EXPRESSO substantially improves existing methods. We apply EXPRESSO to analyze multi-ancestry GWAS datasets for 14 autoimmune diseases. EXPRESSO uniquely identifies 958 novel gene x trait associations, which is 26% more than the second-best method. Among them, 492 are unique to cell type level analysis and missed by TWAS using whole blood. We also develop a cell type aware drug repurposing pipeline, which leverages EXPRESSO results to identify drug compounds that can reverse disease gene expressions in relevant cell types. Our results point to multiple drugs with therapeutic potentials, including metformin for type 1 diabetes, and vitamin K for ulcerative colitis.

Highlights The homogeneous hybridization of organic–inorganic-metal elements in 3D aerogel was achieved by an expeditious method. The aerogel tightly integrates excellent thermal insulation (49.6 mW m−1 K−1), ablative resistance, mechanical strength, and superhydrophobic properties. The ablated carbon aerogel combines notable electromagnetic interference shielding properties (31.6 dB) and load-carrying properties (272.8 kN·m kg−1).

Abstract The dispersion stability of carbonyl iron particle (CIP)-based magnetorheological fluid (MRF) is improved by CIP, which particle is etched with hydrochloric acid (HCl) to form porous structure with many hydroxyl groups and subsequently coated with silane coupling agents that have varying chain lengths. The microstructures, coating effect and magnetism of the CIPs were examined using the Scanning Electron Microscopy, Automatic Surface and Porosity Analyzer (BET), Fourier-Transform Infrared Spectroscopy, Thermogravimetric Analysis and Vibrating Sample Magnetometer. Furthermore, the rheological properties and dispersion stability of the MRFs were assessed using a Rotating Rheometer and Turbiscan-lab. The results revealed that the nanoporous structure appeared on the CIPs and the specific surface area increased remarkably after being etched by hydrochloric acid. Additionally, as the chain length of the silane coupling agent increases, the coated mass on the particles increases, the the density and the saturation magnetization of particles decreased, and the coated particles with different shell thicknesses were obtained; without a magnetic field, the viscosity of MRF prepared by coated particles increase slightly, due to the enhancement of special three-dimensional network structure; under a magnetic field, the viscosity of the MRF decreased distinctly; the sedimentation rate of MRF decreased from 58 to 3.5% after 100 days of sedimentation, and the migration distances of the MRFs were 22.4, 3.7, 2.4, and 0 mm, with particle sedimentation rates of 0.149, 0.019, 0.017, and 0 mm/h, respectively. The MRF with high dispersion stability was obtained, and the etching of CIP by HCl and the proper chain length of the coating of silane coupling agent were proved effective manners to improve the dispersion stability of MRF.

Endometriosis (EMs) is a prevalent chronic gynecological condition that depends on estrogen, marked by the presence of active endometrial tissue (glands and stroma) outside the uterus. Although pathologically benign, it exhibits biological behaviors such as invasion and metastasis akin to malignant tumors. Endometriosis-associated ovarian carcinoma (EAOC), arising from malignant transformation of EMs, poses significant clinical challenges. However, the mechanisms underlying EAOC pathogenesis remain incompletely understood, with a lack of reliable biomarkers for early diagnosis and personalized treatment strategies. Considering the significant number of EMs patients and the extended period during which malignant transformation can occur, EAOC deserves significant attention. Current research both domestically and internationally indicates that the pathogenesis of EAOC is complex, involving genetic mutations, immune microenvironment, oxidative stress, epigenetic changes, and related areas. This review summarizes the mechanisms underlying the development of EAOC.

ObjectiveTo investigate the efficacy of comparing tibia transverse transport (TTT) and periosteal distraction in treating diabetic foot ulcers.MethodsA retrospective analysis of 19 patients with diabetic foot ulcers treated with both procedures between February 2020 and November 2022, 8 of whom were treated with the tibial transverse transfer technique (transfer group) and 11 with the osteochondral distraction technique (distraction group), was performed to compare and analyze the clinical efficacy of the two methods.ResultsAll wounds were healed in both groups, and the healing time ranged from 15 to 41days with a mean of 28d. The limb preservation rate was 100%. The operative time, intraoperative bleeding, and pain score in the operative area were significantly less in the distraction group than in the removal group, with statistically significant differences (P 0.05).ConclusionsThe Periosteal distraction technique can significantly promote the healing of diabetic foot ulcers. It has the same efficacy as TTT in promoting the healing of diabetic foot ulcer wounds and improving the peripheral circulation of affected limbs. In addition, the periosteal distraction technique has the advantages of small trauma, simple operation, few complications, and convenient nursing care.

ABSTRACT: Egg turning in incubation is crucial to the development of embryos and hatching performance. We aimed to develop a high performance duck egg incubation technique by enlarging and changing egg turning angles. Increasing turning angle from 45 to 75° did not affect the embryo early mortality during the first 15 d of incubation, which ranged from 3.5 to 4.0%, but accelerated chorioallantoic membrane (CAM) development by 17 h, and significantly (P < 0.01) reduced the late mortality from 9.4 ± 0.98% to 5.31 ± 0.63%. As the result, fertile egg hatchability increased from 91.03 ± 0.97% to 94.64 ± 0.61% (P < 0.05), so was healthy duckling rate from 87.24 ± 1.17% to 92.08 ± 0.55% (P < 0.05), and duckling live weight from 60.74 ± 0.63 g to 63.15 ± 0.35 g (P < 0.05). Changing turning angle from 75°to 60°during incubation d 15 to 25 further reduced late embryo mortality to 3.88 ± 0.47 and increased hatchability to 96.58 ± 0.68%. This changing angle turning hatched ducklings exhibited the highest growth performance during rearing than those hatched by 45 and 75° egg turning. The enhanced growth rate was paralleled by upregulations of somatotropic axis genes mRNA expression levels of the hypothalamus GHRH, liver GHR and IGF-1 during embryo incubation and duckling rearing. In conclusion, a changing angle egg turning incubation technique, 75°in the first 15 d and 60°thereafter, can enhance CAM development, upregulate somatotropic axis genes expressions, and can maximally improve embryo livability, duckling hatchability and growth performance.

BackgroundCNV in KCTD13 has been identified to influence androgen receptor function via its changes in gene dosage, which might contribute to hypospadias. However, there is lack of population-level evidence to assess the contribution of KCTD13 CNV to hypospadias.Methods349 isolated hypospadias patients were recruited and their genotyping was performed using real-time qPCR. We use Database of Genomic Variants (DGV) and CNV calls from SNP-array intensity data in 1,008 Chinese healthy men as reference.Results11.17% of patients were identified to have KCTD13 CNV deletion, significantly higher than 0.05% in DGV (P 0.05).ConclusionsWe demonstrate KCTD13 CNV deletion is strongly associated with hypospadias and its severity, but duplication is not, characterizing KCTD13 genetic variation in more detail than previously described.

Background: The present study aimed to investigate the relationship between swollen limb circumference and compartment pressure after a snakebite and to evaluate the diagnostic value of the circumference difference between the healthy and affected sides and the circumference growth rate for snake venom-induced compartment syndrome (CS). Method: The study was based on a prospective cohort study of snakebite patients at the emergency department of West China Hospital from May 2021 to October 2022. The snakebite patients were divided into the CS and non-compartment syndrome (NCS) groups. The diagnostic value of the circumference of the swollen limb for the CS after snakebite was evaluated using a receiver-operating characteristic curve analysis, and the cut-off value of the circumference of the swollen limb for CS after snakebite was calculated with sensitivity and specificity. Result: The present study enrolled 115 patients with severely swollen limbs after snakebite. The mean age was 59.1 ± 13.6 years, with 58 (50.4 %) female cases and 57 (49.6 %) male cases. There were 33 (28.7 %) cases where the upper limbs were injured and 82 (71.3 %) cases where the lower limbs were injured. These patients were divided into CS (n = 19) and NCS (n = 96) groups. The area under the curve (AUC) for the 15 cm circumference difference and circumferential growth rate of the upper edge of the patella was 0.683 (95 % CI 0.508 to 0.858, P = 0.037), and 0.685 (95 % CI 0.512 to 0.858, P = 0.035). The optimal cut-off values for the 15 cm circumference difference and circumferential growth rate of the upper edge of the patella to distinguish CS and NCS were 2.8 cm (sensitivity = 76.9 %, specificity = 66.7 %) and 7 % (sensitivity = 76.9 %, specificity = 66.7 %), respectively. Conclusion: Limb circumference measurement is a non-invasive, convenient, effective, and repeatable bedside test that can assist clinicians in the early detection of suspected snake venom-induced CS in patients exhibiting limb swelling after snake bites.

BackgroundCellular senescence (CS) is believed to be a major factor in the evolution of cancer. However, CS-related lncRNAs (CSRLs) involved in colon cancer regulation are not fully understood. Our goal was to create a novel CSRLs prognostic model for predicting prognosis and immunotherapy and exploring its potential molecular function in colon cancer.MethodsThe mRNA sequencing data and relevant clinical information of GDC TCGA Colon Cancer (TCGA-COAD) were obtained from UCSC Xena platform, and CS-associated genes was acquired from the CellAge website. Pearson correlation analysis was used to identify CSRLs. Then we used Kaplan–Meier survival curve analysis and univariate Cox analysis to acquire prognostic CSRL. Next, we created a CSRLs prognostic model using LASSO and multivariate Cox analysis, and evaluated its prognostic power by Kaplan–Meier and ROC curve analysis. Besides, we explored the difference in tumor microenvironment, somatic mutation, immunotherapy, and drug sensitivity between high-risk and low-risk groups. Finally, we verified the functions of MYOSLID in cell experiments.ResultsThree CSRLs (AC025165.1, LINC02257 and MYOSLID) were identified as prognostic CSRLs. The prognostic model exhibited a powerful predictive ability for overall survival and clinicopathological features in colon cancer. Moreover, there was a significant difference in the proportion of immune cells and the expression of immunosuppressive point biomarkers between the different groups. The high-risk group benefited from the chemotherapy drugs, such as Teniposide and Mitoxantrone. Finally, cell proliferation and CS were suppressed after MYOSLID knockdown.ConclusionCSRLs are promising biomarkers to forecast survival and therapeutic responses in colon cancer patients. Furthermore, MYOSLID, one of 3-CSRLs in the prognostic model, could dramatically regulate the proliferation and CS of colon cancer.

High levels of urinary lactate are an increased risk of progression in patients with diabetic kidney disease (DKD). However, it is still unveiled how lactate drive DKD. Epithelial-mesenchymal transition (EMT), which is characterized by the loss of epithelial cells polarity and cell-cell adhesion, and the acquisition of mesenchymal-like phenotypes, is widely recognized a critical contributor to DKD. Here, we found a switch from oxidative phosphorylation (OXPHOS) toward glycolysis in AGEs-induced renal tubular epithelial cells, thus leading to elevated levels of renal lactic acid. We demonstrated that reducing the lactate levels markedly delayed EMT progression and improved renal tubular fibrosis in DKD. Mechanically, we observed lactate increased the levels of histone H3 lysine 14 lactylation (H3K14la) in DKD. ChIP-seq & RNA-seq results showed histone lactylation contributed to EMT process by facilitating KLF5 expression. Moreover, KLF5 recognized the promotor of cdh1 and inhibited its transcription, which accelerated EMT of DKD. Additionally, nephro-specific knockdown and pharmacological inhibition of KLF5 diminished EMT development and attenuated DKD fibrosis. Thus, our study provides better understanding of epigenetic regulation of DKD pathogenesis, and new therapeutic strategy for DKD by disruption of the lactate-drived H3K14la/KLF5 pathway.

During the motion of a knee joint, the instantaneous center of rotation (ICR) of the tibia relative to the femur is not fixed but moves along a curve decided by the joint structure. Adapting to wearer’s personalized knee joint structure is important to improve the wearing comfort and rehabilitation effect of the exoskeleton. The paper proposes a design method of a personalized knee rehabilitation exoskeleton with high human-machine compliance. Firstly, an instantaneous center curve (ICC) generation algorithm is proposed, which extracts feature points of the tibia from the medical images of the wearer’s knee joint, generates ICRs of the tibia at different knee joint angles, and then fits the ICRs into the ICC of the knee joint. Secondly, a four-bar linkage model for the knee joint is applied, and the structure parameters of the linkage are optimized by minimizing the deviations between the ICRs of the linkage and the wearer. Finally, a lower limb rehabilitation exoskeleton is implemented, adopting a lightweight transmission scheme using conjugate cams combined with Bowden cables. The experimental results show that the designed exoskeleton is lightweight and has small relative movement and small interaction forces with the wearer, realizing good wearing comfort and motion compliance.

BackgroundPeripheral neuropathy (PN) is a common neurological disorder, and circulating plasma proteins with causal genetic evidence are a major source of therapeutic targets. This study identifies several potential plasma proteins that are causally related to PN risk, providing new insights into protein-mediated pathogenesis of PN and potential targets for novel therapies.MethodsTo identify potential therapeutic targets for PN, we employed two-sample Mendelian randomization (MR) to identify plasma proteins associated with six common PN. First, we screened for proteins related to PN using genome-wide association studies (GWAS), obtaining genetic data on plasma proteomes from 35,559 Icelanders. Summary data for six common PN, including Carpal Tunnel Syndrome (CTS), Trigeminal Neuralgia (TN), Alcoholic Neuropathy (AIP), Drug-induced Neuropathy (DIP), Diabetic Neuropathy (DP), and Guillain-Barré syndrome (GBS), were obtained from the FinnGen database. Two-sample MR and colocalization analyses were then conducted to further identify protein-PN pairs with presumed causal relationships. Enrichment analysis of positive proteins revealed potential biological processes and pathways. Based on drug-gene interaction analysis, we ultimately identified causal proteins associated with PN that could serve as potential drug targets for treating PN.ResultsThrough MR analysis, we identified eight proteins (UBC12, SEM4C, IL23R, Prothrombin, CBS, Microglobulin, MATN4, COLEC12) with causal relationships to PN. We found that UBC12 is a protective factor for DP and CTS, while the remaining proteins are risk factors. Further colocalization analysis showed a posterior probability of hypothesis 4 (PPH4) less than 0.75, indicating no positive colocalization results were found. From the pathway enrichment analysis, we discovered that the proteins were mainly concentrated in pathways related to defense response to bacterium, receptor signaling pathway via STAT, cell killing, negative regulation of cytokine production, and leukocyte mediated immunity. Finally, in Drug-Gene Interaction database (DGIdb), we identified three protein-coding genes (IL23R, F2, CBS) as potential drug targets for PN.ConclusionMendelian randomization studies confirm the causal relationship between genetically predicted PN-related risk and genetically predicted plasma protein abundance. Plasma proteins, as biomarkers associated with PN, can provide potential drug targets for etiological intervention research in PN.

IntroductionNeuromyelitis Optica spectrum disorder (NMOSD) is an autoimmune disease characterized by anti-aquaporin-4 (AQP4) auto-antibodies. The discovery of antibodies AQP4 and myelin oligodendrocyte glycoprotein (MOG) has expanded our understanding of the pathogenesis of neuromyelitis optica. However, the molecular mechanisms underlying the disease, particularly AQP4-associated optic neuritis (AQP4-ON), remain to be fully elucidated.MethodsIn this study, we utilized Weighted Gene Co-expression Network Analysis (WGCNA) to investigate the transcriptomic profiles of peripheral blood samples from patients with AQP4-ON and MOG-positive optic neuritis (MOG-ON), compared to healthy controls.ResultsWGCNA revealed a brown module (ME brown) strongly associated with AQP4-ON, which correlated positively with post-onset visual acuity decline. A total of 132 critical genes were identified, mainly involved in histone modification and microtubule dynamics. Notably, genes HDAC4, HDAC7, KDM6A, and KDM5C demonstrated high AUC values in ROC analysis, indicating their potential as biomarkers for AQP4-ON.ConclusionOur findings provide novel insights into the molecular signature of AQP4-ON and highlight the potential of systems biology approaches in identifying biomarkers for NMOSD. The identified histone modification genes warrant further investigation for their role in disease pathogenesis and as therapeutic targets.

Diagnosis and treatment of urological tumors, relying on auxiliary data such as medical imaging, while incorporating individual patient characteristics into treatment selection, has long been a key challenge in clinical medicine. Traditionally, clinicians used extensive experience for decision-making, but recent artificial intelligence (AI) advancements offer new solutions. Machine learning (ML) and deep learning (DL), notably convolutional neural networks (CNNs) in medical image recognition, enable precise tumor diagnosis and treatment. These technologies analyze complex medical image patterns, improving accuracy and efficiency. AI systems, by learning from vast datasets, reveal hidden features, offering reliable diagnostics and personalized treatment plans. Early detection is crucial for tumors like renal cell carcinoma (RCC), bladder cancer (BC), and Prostate Cancer (PCa). AI, coupled with data analysis, improves early detection and reduces misdiagnosis rates, enhancing treatment precision. AI’s application in urological tumors is a research focus, promising a vital role in urological surgery with improved patient outcomes. This paper examines ML, DL in urological tumors, and AI’s role in clinical decisions, providing insights for future AI applications in urological surgery.

ObjectiveTo investigate the situation and influencing factors of the economic burden of childhood hand, foot, and mouth disease (HFMD) in Anhui province in the 2018 – 2019 season to provide evidence for health policy development. MethodsIn January 2018, 14 county-level and municipal hospitals in Anhui province were selected as research sites using a multistage stratified random sampling method. The information of 2 941 outpatients and hospitalized children with HFMD who visited the research site from January 2018 to December 2019 was collected by a combination of questionnaire survey, hospital billing system query, and telephone follow-up. The direct and indirect economic burden (median [M], 25th percentile, 75th percentile [P25, P75] in Chinese yuan) of children with HFMD was calculated, and the main influencing factors of the disease economic burden were analyzed. ResultsA total of 2 140 children with HFMD were included in the analysis, including 1 119 outpatients (52.3%) and 1 021 inpatients (47.7%). The direct economic burden of outpatients and inpatients was 216.0 (138.4, 339.0) yuan and 2 740.0 (1 870.6, 3 627.6) yuan, the indirect economic burden was 66.0 (0.0, 132.0) yuan and 264.0 (198.0, 429.0) yuan, and the total economic burden was 299.8 (216.0, 452.0) yuan and 3 088.4 (2 173.1, 4 072.9) yuan, respectively. The results of multivariate unconditional logistic regression analysis showed that the HFMD outpatients with higher average monthly family income were more likely to have a significantly higher total economic burden, but those who were kindergarten children and primary school students were more likely to have a significantly lower total economic burden; while the likelihood of having a higher total economic burden was significantly higher for HFMD inpatients aged 12 – 36 months, whose guardians had a college education and above, and with a hospitalization duration of 6 days and more. ConclusionChildhood HFMD can increase the economic burden of the patient′s family and the society in Anhui province. The age, identity, average monthly family income, guardian′s education level and hospitalization time are the main influencing factors of the economic burden.

BackgroundLong-term exposure to free silica particles will lead to fibrosis of lung tissue, and abnormal expression of microRNA (miRNA) may affect the occurrence and process of fibrosis. ObjectiveTo observed possible intervention effect of miR-204-3p overexpression adenovirus on silicosis fibrosis induced by silica dust using a silicosis rat model via non-exposed intratracheal instillation. MethodsForty SD rats were randomly divided into four groups: control group, silicosis model group, miRNA-NC group, and miR-204-3p intervention group. Under ether anesthesia, rats in the silicosis model group, miRNA-NC group, and miR-204-3p intervention group were injected with 1 mL (50 mg·mL−1) of free silica dust suspension into the trachea, while the control group was injected with the same volume of normal saline. After 30 d of dust exposure, the miR-204-3p intervention group was injected with rno-mir-204 adenovirus vector to overexpress miR-204-3p, and the miRNA-NC group was given empty virus vector. After 30 d of normal feeding, the animals were sacrificed by chloral hydrate anesthesia, and the lung tissue was taken for subsequent experiments. The relative expression level of miR-204-3p in lung tissue of rats in each group was detected by real-time fluorescence quantitative PCR (RT-qPCR). HE staining, Masson staining, and Sirius red staining were used for pathological observation. Immunohistochemistry was used to detect the expression of Fibronectin and Collagen I in lung tissue of rats in each group. RT-qPCR was used to detect the relative gene expression levels of fibrosis markers Fibronectin, Vimentin, Collagen I, and Collagen III in lung tissue of rats in each group. Western blot was used to detect the protein expression levels of fibrosis markers Fibronectin, Vimentin, Collagen I, and Collagen III in lung tissue of rats in each group. ResultsThe anatomical features of lung tissue in the control group were pink lung tissue with soft texture and smooth surface, while those in the silicosis model were grayish white tissue with hard texture and scars and grayish white silicon nodules on the surface. Compared with the silicosis model group, the color of lung tissue in the miR-204-3p intervention group became ruddy, the surface was smooth, and the texture became soft. The staining results showed that the alveolar wall of the control group was thin, there were a small number of capillaries in the alveoli, and the alveolar structure was clear and complete. In the silicosis model group, the alveolar wall became thicker, the pulmonary septum was partially broken, the alveolar structure was defective, and a large amount of collagen fibers were deposited. The alveolar structure of the miR-204-3p intervention group was relatively clear and there was a small amount of collagen fiber deposition. RT-qPCR results showed that compared with the control group, the relative expression levels of miR-204-3p in lung tissue of the silicosis model group and the miRNA-NC group were decreased (P

Abstract Macroautophagy is a process that cells engulf cytosolic materials by autophagosomes and deliver them to lysosomes for degradation. The biogenesis of autophagosomes requires ATG2 as a lipid transfer protein to transport lipids from existing membranes to phagophores. It is generally believed that endoplasmic reticulum is the main source for lipid supply of the forming autophagosomes; whether ATG2 can transfer lipids from other organelles to phagophores remains elusive. In this study, we identified a new ATG2A-binding protein, ANKFY1. Depletion of this endosome-localized protein led to the impaired autophagosome growth and the reduced autophagy flux, which largely phenocopied ATG2A/B depletion. A pool of ANKFY1 co-localized with ATG2A between endosomes and phagophores and depletion of UVRAG, ANKFY1 or ATG2A/B led to reduction of PI3P distribution on phagophores. Purified recombinant ANKFY1 bound to PI3P on membrane through its FYVE domain and enhanced ATG2A-mediated lipid transfer between PI3P-containing liposomes. Therefore, we propose that ANKFY1 recruits ATG2A to PI3P-enriched endosomes and promotes ATG2A-mediated lipid transfer from endosomes to phagophores. This finding implicates a new lipid source for ATG2A-mediated phagophore expansion, where endosomes donate PI3P and other lipids to phagophores via lipid transfer.

This study uses the network flow theory to optimize regional water resource allocation. In order to solve the problem of inefficient utilization of water resources with decentralized decision-making by different administrative units, a regional water resource networking and joint dispatching model with multi-objective nonlinear characteristics based on the network flow theory (hereinafter referred to as the network flow model) is constructed in the study. The network flow model was simulated and applied in the Xin-Sheng area of the Cao'e River, a tributary of the Qiantang River, and the results of the study showed that the network flow model scheduling increased significantly in efficiency compared with the current conventional scheduling, with an increase of 35.24 and 9.91% in the water resource utilization rate in the two typical years of 2019 and 2022, respectively, and showed that 2022, which has less rainfall, has a better effect than 2019. The study concludes that the network flow model can effectively improve the efficiency of water resource utilization, solve the problem of water resource imbalance between cities in the region, and play a positive role in the construction of the national water network. HIGHLIGHTS The aim of this study is to construct a network flow model based on nonlinear multi-objective optimization.; Scheduling objective is to maximize water use under industry-dominated economic conditions.; The network flow model couples incentive compatibility mechanisms between different administrative agents.; Network flow modeling can test whether certain administrative units have over-exploited resources.;

The hematopoietic system is susceptible to ionizing radiation (IR), which can cause acute hematopoietic failure or long-term myelosuppression. As the most primitive cells of the hematopoietic hierarchy, hematopoietic stem cells (HSCs) maintain lifelong hematopoietic homeostasis and promote hematopoietic regeneration during stress. Numerous studies have shown that nuclear and mitochondrial genomes are the main targets of radiation injury in HSCs. More importantly, the damage of DNA may trigger a series of biological responses that largely determine HSC fate following IR exposure. Although some essential pathways and factors involved in DNA injury and damage in HSCs have been revealed, a comprehensive understanding of the biological effects of radiation on HSCs still needs to be improved. This review focuses on recent insights into the molecular mechanisms underlying DNA damage and repair in HSCs after IR. Then summarize corresponding regulatory measures, which may provide a reference for further research in this field.

Abstract Acrylamide (AA) is a neurotoxic and potentially carcinogenic contaminant, usually generated during food processing. MicroRNAs are a class of noncoding small RNAs, which serve essential pathogenic roles in linking exposure to toxic contaminants with their pathological outcomes. Our previous research identified miR‐27a‐5p as a key regulator in AA toxicity, as it induces mitochondria‐dependent apoptosis by targeting Btf3 in rats. However, the mechanisms by which miR‐27a‐5p is regulated to exert its toxic effects remain unclear. Here, the transcription factors that bind to the promoter of miR‐27a‐5p and their potential regulatory functions are investigated in cell lines and rats. The results showed that nuclear factor kappa‐B 1 (NF‐κB1) is a promising transcription factor from bioinformatic analysis. The luciferase reporter assay demonstrated that NF‐κB1 enhances the transcriptional activity of the miR‐27a‐5p promoter, whereas the cleavage under targets and tagmentation assay successfully verified the specific binding sites at −305/−298 bp. Furthermore, the inhibition of NF‐κB1 resulted in the suppression of miR‐27a‐5p expression and its associated target pathways, with additional validation provided by in vivo experimentation. Consequently, the upregulation of miR‐27a‐5p induced by AA and its subsequent intrinsic apoptosis can be attributed to the binding of NF‐κB1 to the miR‐27a‐5p promoter. This binding event may serve as the initial step in the molecular network regulated by miR‐27a‐5p that underlies AA toxicity.

Abstract Accelerating efforts for the Sustainable Development Goals requires understanding their synergies and trade-offs at the national and sub-national levels, which will help identify the key hurdles and opportunities to prioritize them in an indivisible manner for a country. Here, we present the importance of the 17 goals through synergy and trade-off networks. Our results reveal that 19 provinces show the highest trade-offs in SDG13 (Combating Climate Change) or SDG5 (Gender Equality) consistent with the national level, with other 12 provinces varying. 24 provinces show the highest synergies in SDG1 (No Poverty) or SDG6 (Clean Water and Sanitation) consistent with the national level, with the remaining 7 provinces varying. These common but differentiated SDG priorities reflect that to ensure a coordinated national response, China should pay more attention to the provincial situation, so that provincial governments can formulate more targeted policies in line with their own priorities towards accelerating sustainable development.

Abstract Many real-world optimization problems, particularly engineering ones, involve constraints that make finding a feasible solution challenging. Numerous researchers have investigated this challenge for constrained single- and multi-objective optimization problems. In particular, this work extends the boundary update (BU) method proposed by Gandomi and Deb (Comput. Methods Appl. Mech. Eng. 363:112917, 2020) for the constrained optimization problem. BU is an implicit constraint handling technique that aims to cut the infeasible search space over iterations to find the feasible region faster. In doing so, the search space is twisted, which can make the optimization problem more challenging. In response, two switching mechanisms are implemented that transform the landscape along with the variables to the original problem when the feasible region is found. To achieve this objective, two thresholds, representing distinct switching methods, are taken into account. In the first approach, the optimization process transitions to a state without utilizing the BU approach when constraint violations reach zero. In the second method, the optimization process shifts to a BU method-free optimization phase when there is no further change observed in the objective space. To validate, benchmarks and engineering problems are considered to be solved with well-known evolutionary single- and multi-objective optimization algorithms. Herein, the proposed method is benchmarked using with and without BU approaches over the whole search process. The results show that the proposed method can significantly boost the solutions in both convergence speed and finding better solutions for constrained optimization problems.

Sheep are a primary species in animal husbandry. Accurate sheep population counts are vital for managing husbandry practices and preventing grassland overgrazing. Current methods using UAV images are time-consuming and costly. The small size of sheep and complex backgrounds in large-scale areas make accurate extraction challenging. We propose the Small Object Extraction Net (SOENet), a semantic segmentation model with an encoder–decoder structure. The SOENet encoder resizes the original images to three resolutions to extract multi-scale sheep features. A Multi-resolution Context Enhancement (MCE) module is proposed to extract complicated contextual features of sheep by concatenating different scales of feature maps to reduce the possibility of commission errors. To minimize omission errors, a Multi-resolution Feature Fusion (MFF) module is proposed by introducing more scales of features to the encoder, facilitating the sharing and exchange of multi-scale sheep features. Our model outperforms nine deep learning models, with a 7.9% improvement in precision and a 1.2% increase in mIoU. SOENet provides an effective solution for large-scale sheep extraction from various ground objects.

ABSTRACTAccurate extraction of built-up areas is helpful to urban development and map updating. Nighttime light (NTL) data can capture the lighting signal of ground objects. However, most built-up area extraction is conducted on public limited coarse spatial resolution NTL images. The Sustainable Development Science Satellite-1 (SDGSAT-1) provides 10 m spatial resolution panchromatic NTL images, making it possible to map detailed urban lighting structures. In urban extraction, the boundaries of urban areas are easily confused with background objects due to the similar spectral and textual features. To address this problem, we proposed a multi-task deep learning model, CG-CFPANet, to extract illuminated built-up areas by synthesizing SDGSAT-1 NTL data and optical remote sensing images. In CG-CFPANet, a convolutional feature pyramid attention (CFPA) module for better contextual recognition and a concatenation group (CG) module to merge the two remote sensing images are developed. Our proposed CG-CFPANet achieved 1.3% higher precision in built-up area extraction than ten other recently proposed network structures: UNet, UNet++, PSPNet, DeeplabV3, FCN, ExtremeC3Net, SegNet, BiseNet, Res2-UNet, and CBRNet. It shows higher applicability for large-scale built-up area extraction.

Accurate haplotyping facilitates distinguishing allele-specific expression, identifying cis-regulatory elements, and characterizing genomic variations, which enables more precise investigations into the relationship between genotype and phenotype. Recent advances in third-generation single-molecule long read and synthetic co-barcoded read sequencing techniques have harnessed long-range information to simplify the assembly graph and improve assembly genomic sequence. However, it remains methodologically challenging to reconstruct the complete haplotypes due to high sequencing error rates of long reads and limited capturing efficiency of co-barcoded reads. We here present a pipeline, AsmMix, for generating both contiguous and accurate diploid genomes. It first assembles co-barcoded reads to generate accurate haplotype-resolved assemblies that may contain many gaps, while the long-read assembly is contiguous but susceptible to errors. Then two assembly sets are integrated into haplotype-resolved assemblies with reduced misassembles. Through extensive evaluation on multiple synthetic datasets, AsmMix consistently demonstrates high precision and recall rates for haplotyping across diverse sequencing platforms, coverage depths, read lengths, and read accuracies, significantly outperforming other existing tools in the field. Furthermore, we validate the effectiveness of our pipeline using a human whole genome dataset (HG002), and produce highly contiguous, accurate, and haplotype-resolved assemblies. These assemblies are evaluated using the GIAB benchmarks, confirming the accuracy of variant calling. Our results demonstrate that AsmMix offers a straightforward yet highly efficient approach that effectively leverages both long reads and co-barcoded reads for haplotype-resolved assembly.

Sinonasal squamous cell carcinoma (SNSCC) is the most common, high-aggressive sinonasal malignancies that have remained relatively stable poor outcomes over the past decade. As a first-line treatment for SNSCC, surgery plus adjuvant radiotherapy is recommended. However, complete surgical resection may not be appropriate due to the proximity of the nasal cavity and sinuses to key structures such as orbit or intracranial. Currently, immune checkpoint inhibitors (ICIs) have been established as one of the first-line therapies for many solid tumors with unresectable stage. However, evidence on the efficacy of ICIs in sinonasal malignancy is scarce and no ICIs are approved for use in SNSCC up to day. In this report, we report a case of a 64-year-old man with SNSCC treated by multi-protocol exploration. The patient achieved pathological complete response (pCR) after receiving two cycles of Docetaxel and cisplatin combined with tislelizumab. To the best of our knowledge, this is the first case of SNSCC treated with tislelizumab that achieved pCR. This case offers real-world evidence that chemotherapy plus immunotherapy is a promising treatment for SNSCC.

Background: Currently, there are few studies on immune-related prognostic analysis of hepatocellular carcinoma (HCC). Our aim was to establish an immune-correlated prognostic model for HCC. Methods: Immune-associated cells were obtained from the scRNA-seq dataset (GSE149614) of HCC. Differentially expressed genes between normal and tumor cells from immune-associated cells and the immune-related genes from the ImmPort database were used to identify immune-related differentially expressed genes (IRDEGs). Subsequently, the risk model was established in the TCGA-LIHC cohort (n = 438) from the Cancer Genome Atlas (TCGA) database by using Kaplan-Meier (K-M) survival curve, univariate/multivariate Cox regression analysis. Subsequently, we further analyzed tumor immune microenvironment characteristics, somatic mutation, immune checkpoint and its ligand expression levels between high- and low-risk groups, as well as drug sensitivity prediction. ICGC cohort was set as the validation cohort. TCGA-LIHC cohort and three independent the Gene Expression Omnibus (GEO) datasets (GSE54236, GSE14520, and GSE64041) was used to verify IRDEGs expression, as well as PCR assays using clinical samples. Results: The IRDEGs was composed of 4 genes, namely B2M, SPP1, PPIA, and HRG. The 438 HCC patients were divided into high- and low-risk group. The high-risk group was associated with poor prognosis, including higher T stage, advanced pathological stages, less immune cell infiltration, higher TP53 mutation rate, the high expression of CTLA4 and HAVCR2. Besides, high-risk populations benefit from most chemotherapy drugs. Similarly, the performance of the risk model was validated in the ICGC. All four datasets (TCGA-LIHC cohort, GSE54236, GSE14520, and GSE64041) and clinical q-PCR results demonstrated that, compared with normal samples, the expressions of B2M and HRG were lower in tumor samples, and the expression of SPP1 was higher. Conclusion: In summary, the immune-related prognostic signature had a good predictive performance on prognosis and immunotherapy for HCC patients.

ABSTRACT: Honokiol is a multifunctional polyphenol present in Magnolia officinalis. The effects of honokiol as a supplement in broiler chicken diets, and the underlying mechanisms, remain unclear. Therefore, the aim of the present study was to investigate the effects of honokiol on the growth performance, antioxidant capacity, and intestinal histomorphology of broiler chickens and to explore the underlying mechanisms. In total, 240 one-day-old broilers were randomly allocated to 5 dietary treatments, with 6 replicate pens and 8 birds per pen. Birds were fed a basal diet supplemented with 0 (blank control, BC), 100, 200, or 400 mg/kg honokiol (H100, H200, and H400), or 200 mg/kg bacitracin zinc (PC) for 42 d. The results showed that H200 and H400 increased body weight gain (BWG) and decreased feed conversion ratio (FCR) during the starter period (P < 0.05). H100 and H200 increased total superoxide dismutase (T-SOD) activity in the serum and decreased malondialdehyde (MDA) amount in the jejunum on d 42 (P < 0.05). Moreover, H100 increased villus height-to-crypt depth ratio in both the jejunum and ileum on d 21 (P < 0.05). PCR analysis showed that honokiol upregulated intestinal expression of glutathione peroxidase (GSH-Px) and downregulated intestinal expression of inducible nitric oxide synthase (iNOS) on d 42 (P < 0.05). The Shannon index, which represents the microbial alpha diversity, was reduced for the PC, H200, and H400 groups. Notably, honokiol treatment altered the cecal microbial community structure and promoted the enrichment of several bacteria, including Firmicutes and Lactobacillus. Higher production of short-chain fatty acids was observed in the cecal digesta of H100 birds, accompanied by an enriched glycolysis/gluconeogenesis pathway, according to the functional prediction of the cecal microbiota. This study provides evidence that honokiol improves growth performance, antioxidant capacity, and intestinal health of broiler chickens, possibly by manipulating the composition and function of the microbial community.

Aim We aimed to explore a new and readily available practical marker for rapidly progressive interstitial lung disease (RP-ILD) and poor short-term outcomes in patients with idiopathic inflammatory myopathies (IIM).Methods A total of 1822 consecutive patients with IIM between 2009 and 2021 were evaluated retrospectively. All proven cases of naïve ILD with complete medical records were included. Red cell distribution width (RDW) values at the initial stage, 3 months and last follow-up were collected. The clinical characteristics and outcomes of the patients were recorded.Results We identified 532 patients with IIM with an average follow-up of 4 years. ILD prevalence was higher in patients of elevated RDW (p0 was higher in patients with RP-ILD and positive for anti-melanoma differentiation-associated gene 5 antibody who died within 3 months (87.5%) compared with those alive at 3 months (24.6%) (p

Based on the essential fatty acids (EFA) precision nutrition, a blend oil (BO) of fish oil and terrestrial oils was developed, and applied successfully to the low marine diets of golden pompano (Trachinotus ovatus). To evaluate whether medium- and short-chain fatty acids (MCFA and SCFA), efficient energy supplements for animals, can spare the dietary EFA, four iso-proteic (48%) and iso-lipidic (11%) low fishmeal (FM) diets (D1-D4, contained 6% FM) were formulated and fed T. ovatus juveniles (initial weight ∼8.50 g) for 9 weeks in sea cages. Control diets (D1) contained 8% BO, while the BO of diets D2-D4 were replaced 50% with coconut oil, coconut oil + sodium butyrate, and coconut oil + n-3 LC-PUFA enriched oil, respectively. The results showed that compared to the D1 group, the growth performance of D2 and D3 were significantly lower, while a comparable growth was detected in the D4 group. The muscle and hepatic n-3 PUFA levels in the D2 and D3 groups were significantly low, and these fatty acid contents were modified in the D4 group. Meanwhile, the muscle textural firmness of the D2-D4 groups was decreased. Regarding the health index of fish, compared to the D1 group, high serum triglyceride (TG) contents and low HDL/LDL ratio were detected in the D2-D4 groups, and high ACP, AST, and ALT activities were observed in these groups. Meanwhile, high HSI and low hepatic enzymatic activities of CAT and ALT were measured in the D2-D3 groups. Additionally, the mRNA levels of hepatic fatty acid synthesis-related genes (fas, acc, and pparγ) were significantly increased in D2-D4 groups, and the expression levels of lipid catabolism genes (cpt-1 and lpl) showed an upward trend. Moreover, the D2 group exhibited the lowest intestinal wall thickness, the mRNA levels of intestine anti-inflammatory cytokines (il-10) were up-regulated in the D2-D4 groups, and the highest mRNA levels of pro-inflammatory cytokines (il-8) were detected in the D2 group. In conclusion, the EFA deficiency leads to a decline in the growth and muscle quality of T. ovatus fed low marine diets, which cannot be mitigated by the addition of medium-short chain fatty acids. The results indicated that MCFA and SCFA cannot spare the EFA of low marine diets in T. ovatus.