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Objective The objective of this study was to investigate the effects of prolactin (PRL) on the proliferation and apoptosis of ovine ovarian granulosa cells (GCs) and the secretion of estrogen (E2) and progesterone (P4), as well as to explore the effects of PRL on related genes and proteins. Methods We isolated ovarian GCs from 1-year-old small-tail Han sheep and identified PRL receptor (PRLR) on ovaries and follicle stimulating hormone receptor (FSHR) on ovarian GCs, respectively, using immunohistochemistry. PRL (0, 0.05, 0.50, 5.00 μg/mL) were added to GCs in vitro along with FSH, cell proliferation was measured by cell counting Kit-8 (CCK-8) and apoptosis by flow cytometry. The measurement of E2 and P4 content by enzyme-linked immunosorbent assays after 48 h and 72 h. The expression of functional genes and proteins was identified by real-time quantitative polymerase chain reaction (RT-qPCR) and Western-blot after 48 h. Results PRLR was expressed in both follicular GCs and corpus luteum, whereas FSHR was expressed specifically. The proliferative activity was lower on day 1 while higher on day 4 and day 5. The apoptosis rate of GCs in the 0.05 μg/mL group was significantly higher than that in the control group after treatment with PRL for 24 h (p

Abstract High-grade serous ovarian carcinoma (HGSOC) is one of the most lethal gynecological cancer. Genetic studies have revealed gene copy number alterations (CNAs) frequently occurred in HGSOC pathogenesis, however the function and mechanism of CNAs for microRNAs are still not fully understood. Here, we show the dependence on gene copy number amplification of MIR937 that enhances cell autophagy and dictates HGSOC proliferative activity. Data mining of TCGA database revealed MIR937 amplification is correlated with increased MIR937 expression and cell proliferation of HGSOC. Deletion of MIR937 in HGSOC cells led to impaired autophagy and retarded cell proliferation, and the extent for its inhibitory effects scaled with the degree of MIR937 copy loss. Rescue assay confirmed miR-937-5p, a mature product of MIR937, was sufficient to restore its oncogenic function. Mechanistically, MIR937 amplification raised the expression of miR-937-5p, enhanced its binding to 3′ UTR of FBXO16 transcript, and thereby restricting FBXO16 degradative effects on ULK1. Our results demonstrate that MIR937 amplification augments cell autophagy and proliferation, and suggest an alternative strategy of MIR937/FBXO16/ULK1 targeting for HGSOC treatment.

Abstract Factor XII (FXII) is the zymogen of the plasma protease FXIIa that activates the intrinsic coagulation pathway and the kallikrein kinin-system. The role of FXII in inflammation has been obscure. Here, we report a single-domain antibody (nanobody, Nb) fused to the Fc region of a human immunoglobulin (Nb-Fc) that recognizes FXII in a conformation-dependent manner and interferes with FXIIa formation. Nb-Fc treatment inhibited arterial thrombosis in male mice without affecting hemostasis. In a mouse model of extracorporeal membrane oxygenation (ECMO), FXII inhibition or knockout reduced thrombus deposition on oxygenator membranes and systemic microvascular thrombi. ECMO increased circulating levels of D-dimer, alkaline phosphatase, creatinine and TNF-α and triggered microvascular neutrophil adherence, platelet aggregation and their interaction, which were substantially attenuated by FXII blockade. Both Nb-Fc treatment and FXII knockout markedly ameliorated immune complex-induced local vasculitis and anti-neutrophil cytoplasmic antibody-induced systemic vasculitis, consistent with selectively suppressed neutrophil migration. In human blood microfluidic analysis, Nb-Fc treatment prevented collagen-induced fibrin deposition and neutrophil adhesion/activation. Thus, FXII is an important mediator of inflammatory responses in vasculitis and ECMO, and Nb-Fc provides a promising approach to alleviate thrombo-inflammatory disorders.

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

Abstract Polyamorphic transition (PT) is a compelling and pivotal physical phenomenon in the field of glass and materials science. Understanding this transition is of scientific and technological significance, as it offers an important pathway for effectively tuning the structure and property of glasses. In contrast to the PT observed in conventional metallic glasses (MGs), which typically exhibit a pronounced first-order nature, herein we report a continuous PT (CPT) without first-order characteristics in high-entropy MGs (HEMGs) upon heating. This CPT behavior is featured by the continuous structural evolution at the atomic level and an increasing chemical concentration gradient with temperature, but no abrupt reduction in volume and energy. The continuous transformation is associated with the absence of local favorable structures and chemical heterogeneity caused by the high configurational entropy, which limits the distance and frequency of atomic diffusion. As a result of the CPT, numerous glass states can be generated, which provides an opportunity to understand the nature, atomic packing, formability, and properties of MGs. Moreover, this discovery highlights the implication of configurational entropy in exploring polyamorphic glasses with an identical composition but highly tunable structures and properties.

Abstract Developing light yet strong aluminum (Al)-based alloys has been attracting unremitting efforts due to the soaring demand for energy-efficient structural materials. However, this endeavor is impeded by the limited solubility of other lighter components in Al. Here, we propose to surmount this challenge by converting multiple brittle phases into a ductile solid solution in Al-based complex concentrated alloys (CCA) by applying high pressure and temperature. We successfully develop a face-centered cubic single-phase Al-based CCA, Al55Mg35Li5Zn5, with a low density of 2.40 g/cm3 and a high specific yield strength of 344×103 N·m/kg (typically ~ 200×103 N·m/kg in conventional Al-based alloys). Our analysis reveals that formation of the single-phase CCA can be attributed to the decreased difference in atomic size and electronegativity between the solute elements and Al under high pressure, as well as the synergistic high entropy effect caused by high temperature and high pressure. The increase in strength originates mainly from high solid solution and nanoscale chemical fluctuations. Our findings could offer a viable route to explore lightweight single-phase CCAs in a vast composition-temperature-pressure space with enhanced mechanical properties.

Background: Minimal residual disease (MRD) testing is a promising approach to tailor the treatment of multiple myeloma (MM). However, several major concerns remain to be addressed before moving it into daily practice, most of which stem from the dynamic nature of the MRD status. Thus, it is crucial to understand the MRD dynamics and propose its clinical implications. Methods: We retrospectively analysed the data of patients with newly diagnosed MM (NDMM) who had flow cytometry-based MRD tests at multiple time points after initiation of therapy. The impact of undetectable MRD (including attainment, duration and loss) on clinical outcomes was analysed. Results: In a cohort of 220 patients with NDMM, attainment of MRD− offered favourable outcomes (P < 0.0001 for both progression-free survival (PFS) and overall survival (OS)), regardless of baseline risk factors. Notably, MRD− duration ≥12 months was associated with an 83 % (95 % confidence interval (CI), 0.09−0.34; P < 0.0001) or 69 % (95 % CI, 0.13−0.76; P = 0.0098) reduction in risk of progression/death or death, while the longer MRD− was sustained, the better the outcome was. Loss of MRD− led to poor PFS (hazard ratio (HR) 0.01, 95 % CI 0–0.06, P < 0.0001) and OS (HR 0.03, 95 % CI 0–0.24, P = 0.0008). Most patients (70 %) who lost MRD− status carried high-risk cytogenetic abnormalities (HRCAs). While MRD− was temporally inconsistent with conventional therapeutic responses (eg ≥ complete remission or very good partial response), it predicted disease progression or recurrence more robustly than the latter. Last, the predictive value of the MRD status was independent of baseline risk factors (eg high-risk cytogenetic abnormality, International Staging System (ISS) or Revised (R-)ISS staging). Conclusions: Longitudinal assessment of MRD during the treatment course and follow-up is required for monitoring disease progression or relapse, to guide treatment decisions. Accordingly, a prospective study is currently ongoing to investigate the feasibility and benefit of the MRD-tailored therapy according to the longitudinal changes of the MRD status.

Introduction Pancreatic portal hypertension (PPH) is a rare complication of acute pancreatitis (AP) that can lead to severe gastrointestinal bleeding. The risk factors associated with PPH, as well as the overall prognosis, warrant further investigation. This study aims to develop and validate a nomogram to predict PPH in patients with AP.Methods Consecutive patients with AP from 2015 to 2023 were retrospectively included in the study. Demographic data, clinical manifestations within the first week of AP onset, and initial contrast-enhanced CT findings were used to develop the predictive model. Univariate and multivariate Cox regression analyses were performed to identify risk factors for PPH. Based on the results of the multivariate analysis, a nomogram was developed. The patients were randomly divided into training and validation sets at a 7:3 ratio. The accuracy and discriminative power of the predictive model were assessed using the area under the curve (AUC) from the receiver operating characteristic curve and the calibration curve.Results Of the 1473 patients with AP, 107 (7.3%) developed PPH within 6 months (range: 2–22 months) during follow-up. Multivariate regression analysis showed that body mass index (BMI) (HR, 1.10; 95% CI 1.04 to 1.16; p=0.001), moderately severe grade (HR, 9.36; 95% CI 4.58 to 19.13; p

To avoid carbonate precipitation for CO2 electrolysis, developing CO2 conversion in an acid electrolyte is viewed as an ultimately challenging technology. In Nature, Xia et al. recently explored a proton-exchange membrane system for reducing CO2 to formic acid with a Pb–PbSO4 composite catalyst derived from waste lead-acid batteries based on the lattice carbon activation mechanism. Up to 93% Faradaic efficiency was realized when formic acid was produced by this technology.

Abstract Background Ischemic cardio-cerebrovascular disease is the leading cause of mortality worldwide. However, studies focusing on elderly and very elderly patients are scarce. Hence, our study aimed to characterize and investigate the long-term prognostic implications of ischemic cardio-cerebrovascular diseases in elderly Chinese patients. Methods This retrospective cohort study included 1026 patients aged ≥ 65 years who were categorized into the mono ischemic cardio-cerebrovascular disease (MICCD) (either coronary artery disease or ischemic stroke/transient ischemic attack) (n = 912) and the comorbidity of ischemic cardio-cerebrovascular disease (CICCD) (diagnosed with both coronary artery disease and ischemic stroke/transient ischemic attack at admission) (n = 114). The primary outcome was all-cause death. The mortality risk was evaluated using the Cox proportional hazards risk model with multiple adjustments by conventional and propensity-score-based approaches. Results Of the 2494 consecutive elderly patients admitted to the hospital, 1026 (median age 83 years [interquartile range]: 76.5–86.4; 94.4% men) met the inclusion criteria. Patients with CICCD consisted mostly of very elderly (79.2% vs. 66.1%, P

Abstract It remains a substantial challenge to balance treatment efficacy and toxicity in geriatric patients with multiple myeloma (MM), primarily due to the dynamic nature of frailty. Here, we conducted a prospective study to evaluate the feasibility and benefits of dynamic frailty-tailored therapy (DynaFiT) in elderly patients. Patients with newly diagnosed MM (aged ≥ 65 years) received eight induction cycles of bortezomib, lenalidomide, and dexamethasone (daratumumab was recommended for frail patients), with treatment intensity adjusted according to longitudinal changes in the frailty category (IMWG-FI) at each cycle. Of 90 patients, 33 (37%), 16 (18%), and 41 (45%) were fit, intermediate fit, and frail at baseline, respectively. Of 75 patients who had geriatric assessment at least twice, 28 (37%) experienced frailty category changes at least once. At analysis, 15/26 (58%) frail patients improved (27% became fit and 31% became intermediate fit), 4/15 (27%) intermediate fit patients either improved or deteriorated (two for each), and 6/30 (20%) fit patients deteriorated. During induction, 34/90 (38%) patients discontinued treatment, including 10/33 (30%) fit, 4/16 (25%) intermediate fit, and 20/41 (49%) frail; 14/40 (35%) frail patients discontinued treatment within the first two cycles, mainly because of non-hematologic toxicity (mostly infections). For fit, intermediate-fit, and frail patients, the overall response rate was 100%, 93%, and 73%, respectively; one-year overall survival was 90%, 75%, and 54%, respectively. Therefore, the individualized DynaFiT is feasible and promising for heterogeneous elderly patients.

IntroductionPregnancy toxemia (PT) is a nutritional metabolic disease of ewes in late pregnancy. This study aimed to reveal the relationship between rumen microbiota and PT.MethodsWe selected 10 healthy ewes (CON) and 10 pregnancy toxemia ewes (PT) at 135 days of gestation according to the blood β-hydroxybutyrate (BHBA), glucose (Glu) concentrations and clinical symptoms. Blood and rumen fluid were collected before morning feeding to determine serum biochemical indices and rumen fermentation parameters. Total DNA of rumen fluid was extracted and the V3-V4 regions of 16S rRNA were amplified by PCR for high-throughput sequencing.ResultsThe results showed that the serum concentrations of Glu, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), uric acid (UA), creatinine (Cr), acetate, propionate, butyrate, and microbial crude protein (MCP) were decreased (p

Abstract For lithium‐sulfur batteries (Li‐S batteries), a high‐content electrolyte typically can exacerbate the shuttle effect, while a lean electrolyte may lead to decreased Li‐ion conductivity and reduced catalytic conversion efficiency, so achieving an appropriate electrolyte‐to‐sulfur ratio (E/S ratio) is essential for improving the battery cycling efficiency. A quasi‐solid electrolyte (COF‐SH@PVDF‐HFP) with strong adsorption and high catalytic conversion was constructed for in situ covalent organic framework (COF) growth on highly polarized polyvinylidene fluoride‐hexafluoropropylene (PVDF‐HFP) fibers. COF‐SH@PVDF‐HFP enables efficient Li‐ion conductivity with low‐content liquid electrolyte and effectively suppresses the shuttle effect. The results based on in situ Fourier‐transform infrared, in situ Raman, UV–Vis, X‐ray photoelectron, and density functional theory calculations confirmed the high catalytic conversion of COF‐SH layer containing sulfhydryl and imine groups for the lithium polysulfides. Lithium plating/stripping tests based on Li/COF‐SH@PVDF‐HFP/Li show excellent lithium compatibility (5 mAh cm−2 for 1400 h). The assembled Li‐S battery exhibits excellent rate (2 C 688.7 mAh g−1) and cycle performance (at 2 C of 568.8 mAh g−1 with a capacity retention of 77.3% after 800 cycles). This is the first report to improve the cycling stability of quasi‐solid‐state Li‐S batteries by reducing both the E/S ratio and the designing strategy of sulfhydryl‐functionalized COF for quasi‐solid electrolytes. This process opens up the possibility of the high performance of solid‐state Li‐S batteries.

Cervical cancer ranks fourth in women in terms of incidence and mortality. The RNA-binding protein YTH N6-methyladenosine RNA-binding protein F2 (YTHDF2) contributes to cancer progression by incompletely understood mechanisms. We show how YTHDF2 controls the fate of cervical cancer cells and whether YTHDF2 could be a valid target for the therapy of cervical cancer. Sphere formation and alkaline phosphatase staining assays were performed to evaluate tumor stemness of cervical cancer cells following YTHDF2 knockdown. Apoptosis was detected by flow cytometry and TUNEL assay. The compounds 4PBA and SP600125 were used to investigate the correlation between JNK, endoplasmic reticulum stress, tumor stemness, and apoptosis. Data from The Cancer Genome Atlas (TCGA) databases and Gene Expression Omnibus (GEO) revealed that GLI family zinc finger 2 (GLI2) might be the target of YTHDF2. The transcription inhibitor actinomycin D and dual-luciferase reporter gene assays were employed to investigate the association between the GLI2 mRNA and YTHDF2. Nude mouse xenografts were generated to assess the effects of YTHDF2 knockdown on cervical cancer growth in vivo. Knockdown of YTHDF2 up-regulated the expression of GLI2, leading to JNK phosphorylation and endoplasmic reticulum stress. These processes inhibited the proliferation of cervical cancer cells and their tumor cell stemness and promotion of apoptosis. In conclusion, the knockdown of YTHDF2 significantly affects the progression of cervical cancer cells, making it a potential target for treating cervical cancer.

Abstract The extraction of targets from biological samples for immunoassays using organic solvents, such as methanol, is often necessary. However, high concentrations of organic solvents in extracts invariably lead to instability of the employed antibody, resulting in poor performance of the immunoassay. Evaluating the tolerance ability and exploring the molecular mechanisms of antibody tolerance in organic solvents are essential for the development of robust immunoassays. In this work, 25 monoclonal antibodies and methanol are utilized as models to address these questions. A novel protocol is initially established to precisely and rapidly determine antibody tolerance in methanol, identifying two distinct methanol effect patterns. Through a detailed investigation of the structural basis, a novel hypothesis regarding methanol effect patterns is proposed, termed “folding‐aggregation,” which is subsequently validated through molecular dynamics simulations. Furthermore, the investigation of sequence basis reveals significant differences in residue types within the complementarity‐determining regions and ligand‐binding residues, distinguishing the two antibody methanol effect patterns. Moreover, the methanol effect patterns of the antibodies are defined by germline antibodies. This work represents the first exploration of antibody methanol effect patterns and associated molecular mechanisms, with potential implications for the discovery and engineering of tolerant antibodies for the development of robust immunoassays.

Abstract Background Cutaneous squamous cell carcinoma (cSCC) develops from epithelial keratinocytes by dysregulation of self-renewal and differentiation. Recent studies have found that the size and number of cSCC tumors gradually decrease or even disappear after HPV vaccination. However, the role of the HPV vaccine in the cSCC mechanism is poorly understood. Objective The aim of this study is to investigate the effect and mechanism of the HPV vaccine in cSCC. Methods Immunofluorescence was used to study the immune infiltrating cells in the tumor tissues of patients with cSCC. The effects of the HPV vaccine on cSCC cells and tissues were studied by Cell Culture, Real-time PCR, Western Blot, Cytotoxicity Assay, Enzyme-linked Immunosorbent Assay, m6A Blotting, CCK-8 Assay, m6A Ribonucleic acid Methylation Quantification and tumor transplantation. Results The HPV vaccine enhanced the toxic effect of CD8+T cells on cSCC cells and promoted the secretion of multiple cytokines by CD8+T cells. In addition, HPV vaccines can increase tumor sensitivity to anti-PD-1 therapy by downregulating METTL3 in tumor tissue, with the combination of HPV vaccine and PD-1 monoclonal antibodies producing enhanced immune cell infiltration compared to PD-1 blockade alone. Study limitations It is important to note the limitations of this study, including the small sample size, the construction of the mouse model, and the choice of HPV vaccine and PD-1 monoclonal antibody, which may limit the generalization of our findings to a wider population. Conclusions It is hoped that this research will contribute to a deeper understanding of the role of the HPV vaccine in the treatment of cSCC. HPV vaccine is expected to become an important approach to alleviate the development of cSCC.

Abstract The IVa subfamily of glycine-rich proteins (GRPs) comprises a group of glycine-rich RNA binding proteins referred to as GR-RBPa here. Previous studies have demonstrated functions of GR-RBPa proteins in regulating stress response in plants. However, the mechanisms responsible for the differential regulatory functions of GR-RBPa proteins in different plant species have not been fully elucidated. In this study, we identified and comprehensively studied a total of 34 GR-RBPa proteins from five plant species. Our analysis revealed that GR-RBPa proteins were further classified into two branches, with proteins in branch I being relatively more conserved than those in branch II. When subjected to identical stresses, these genes exhibited intensive and differential expression regulation in different plant species, corresponding to the enrichment of cis-acting regulatory elements involving in environmental and internal signaling in these genes. Unexpectedly, all GR-RBPa genes in branch I underwent intensive alternative splicing (AS) regulation, while almost all genes in branch II were only constitutively spliced, despite having more introns. This study highlights the complex and divergent regulations of a group of conserved RNA binding proteins in different plants when exposed to identical stress conditions. These species-specific regulations may have implications for stress responses and adaptations in different plant species.

Aqueous zinc-ion batteries (AZIBs) have recently attracted worldwide attention due to the natural abundance of Zn, low cost, high safety, and environmental benignity. Up to the present, several kinds of cathode materials have been employed for aqueous zinc-ion batteries, including manganese-based, vanadium-based, organic electrode materials, Prussian Blues, and their analogues, etc. Among all the cathode materials, manganese (Mn)-based oxide cathode materials possess the advantages of low cost, high theoretical specific capacity, and abundance of reserves, making them the most promising cathode materials for commercialization. However, several critical issues, including intrinsically poor conductivity, sluggish diffusion kinetics of Zn2+, Jahn–Teller effect, and Mn dissolution, hinder their practical applications. This Review provides an overview of the development history, research status, and scientific challenges of manganese-based oxide cathode materials for aqueous zinc-ion batteries. In addition, the failure mechanisms of manganese-based oxide materials are also discussed. To address the issues facing manganese-based oxide cathode materials, various strategies, including pre-intercalation, defect engineering, interface modification, morphology regulation, electrolyte optimization, composite construction, and activation of dissolution/deposition mechanism, are summarized. Finally, based on the analysis above, we provide future guidelines for designing Mn-based oxide cathode materials for aqueous zinc-ion batteries.

Abstract Background Most disease resistance (R) genes in plants encode proteins that contain leucine-rich-repeat (LRR) and nucleotide-binding site (NBS) domains, which belong to the NBS-LRR family. The sequenced genomes of Fusarium wilt-susceptible Vernicia fordii and its resistant counterpart, Vernicia montana, offer significant resources for the functional characterization and discovery of novel NBS-LRR genes in tung tree. Results Here, we identified 239 NBS-LRR genes across two tung tree genomes: 90 in V. fordii and 149 in V. montana. Five VmNBS-LRR paralogous were predicted in V. montana, and 43 orthologous were detected between V. fordii and V. montana. The orthologous gene pair Vf11G0978-Vm019719 exhibited distinct expression patterns in V. fordii and V. montana: Vf11G0978 showed downregulated expression in V. fordii, while its orthologous gene Vm019719 demonstrated upregulated expression in V. montana, indicating that this pair may be responsible for the resistance to Fusarium wilt in V. montana. Vm019719 from V. montana, activated by VmWRKY64, was shown to confer resistance to Fusarium wilt in V. montana by a virus-induced gene silencing (VIGS) experiment. However, in the susceptible V. fordii, its allelic counterpart, Vf11G0978, exhibited an ineffective defense response, attributed to a deletion in the promoter’s W-box element. Conclusions This study provides the first systematic analysis of NBS-LRR genes in the tung tree and identifies a candidate gene that can be utilized for marker-assisted breeding to control Fusarium wilt in V. fordii.

Prolactin (PRL) plays a key role in the growth and ovulation of animal follicles, but its impact on follicular recruitment in ewes remains uncertain. In this study, a total of sixteen healthy ewes (Hu sheep, aged 2–3 years, with continuous reproduction and housed separately), matched for parity and weight (52.98 ± 0.96 kg), were randomly assigned to two groups: a control group (C) and a treatment group (T, PRL inhibition). Ovaries were collected in vivo after anesthesia during the estrus stage, and tissue morphology was observed using hematoxylin–eosin (HE) staining. By using RNA sequencing on the ovaries of C and T groups and conducting bioinformatics analysis, the essential genes and pathways involved in the regulation of PRL inhibition were pinpointed. Subcellular localization of key genes in ovarian tissue was determined using a fluorescence in situ hybridization (FISH) assay and immunohistochemistry. The function of key genes was validated using knockout and overexpression techniques. During the estrus phase, we noted a marked rise in the count of large follicles within ovarian tissue following the inhibition of prolactin. In total, 328 differentially expressed genes (DEGs) were detected, with 162 upregulated and 166 downregulated. The results indicated that inhibiting PRL primarily influences follicle recruitment by acting on the target gene PIKfyve. Following the inhibition of PRL during the estrus phase, there was an increase in the expression of PIKfyve. PIKfyve was primarily localized in the ovarian granulosa cells (GCs) and cumulus cells (CCs) in the ovarian tissue of ewes. The overexpression of PIKfyve decreased cell apoptosis and enhanced steroid hormone release, whereas knockout of PIKfyve had the reverse effect. In conclusion, PRL inhibition promoted follicle recruitment in ewes by upregulating PIKfyve during the estrus stage.

Prolactin (PRL) has recently been found to play a role in lipid metabolism in addition to its traditional roles in lactation and reproduction. However, the effects of PRL on lipid metabolism in liver and adipose tissues are unclear. Therefore, we aimed to study the role of PRL on lipid metabolism in goats. Twenty healthy eleven-month-old Yanshan cashmere goats with similar body weights (BWs) were selected and randomly divided into a control (CON) group and a bromocriptine (BCR, a PRL inhibitor, 0.06 mg/kg, BW) group. The experiment lasted for 30 days. Blood was collected on the day before BCR treatment (day 0) and on the 15th and 30th days after BCR treatment (days 15 and 30). On day 30 of treatment, all goats were slaughtered to collect their liver, subcutaneous adipose, and perirenal adipose tissues. A portion of all collected tissues was stored in 4% paraformaldehyde for histological observation, and another portion was immediately stored in liquid nitrogen for RNA extraction. The PRL inhibition had inconclusive effects found on BW and average daily feed intake (ADFI) in goats (p > 0.05). PRL inhibition decreased the hormone-sensitive lipase (HSL) levels on day 30 (p < 0.05), but the effects were inconclusive on days 0 and 15. PRL inhibition had inconclusive effects found on total cholesterol (TCH), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fatty acid synthase (FAS), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), and acetyl-CoA carboxylase (ACC) on days 0, 15, and 30 (p > 0.05). Furthermore, hematoxylin–eosin (HE) staining of the liver, subcutaneous adipose, and perirenal adipose sections showed that PRL inhibition had inconclusive effects on the pathological changes in their histomorphology (p > 0.05), but measuring adipocytes showed that the area of perirenal adipocytes decreased in the BCR group (p < 0.05). The qPCR results showed that PRL inhibition increased the expression of PRL, long-form PRL receptor (LPRLR), and short-form PRL receptor (SPRLR) genes, as well as the expression of genes related to lipid metabolism, including sterol regulatory element binding transcription factor 1 (SREBF1); sterol regulatory element binding transcription factor 2 (SREBF2); acetyl-CoA carboxylase alpha (ACACA); fatty acid synthase (FASN); 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR); 7-dehydrocholesterol reductase (DHCR7); peroxisome proliferator-activated receptor gamma (PPARG); and lipase E, hormone-sensitive type (LIPE) in the liver (p < 0.05). In the subcutaneous adipose tissue, PRL inhibition increased SPRLR gene expression (p < 0.05) and decreased the expression of genes related to lipid metabolism, including SREBF1, SREBF2, ACACA, PPARG, and LIPE (p < 0.05). In the perirenal adipose tissue, the inhibition of PRL decreased the expression of the PRL, SREBF2, and HMGCR genes (p < 0.05). In conclusion, the inhibition of PRL decreases the serum HSL levels in cashmere goats; the effects of PRL on lipid metabolism are different in different tissues; and PRL affects lipid metabolic activity by regulating different PRLRs in liver and subcutaneous adipose tissues, as well as by decreasing the expression of the PRL, SREBF2, and HMGCR genes in perirenal adipose tissue.

The objective of this study was to investigate the differences in the energy metabolites, immunity, antioxidant capacity, and rumen microbiota of ewes with different numbers of fetuses. Thirty healthy ewes were selected and divided into single- (SL, n = 10), twin- (TL, n = 10), and triplet-fetal (PL, n = 10) ewes according to the number of fetuses. Sampling was carried out on days 21 (Q21) and 7 (Q7) before lambing. The results show no differences (p > 0.05) in the DMI and BW of ewes with different numbers of fetuses, and the body condition score (BCS) of PL ewes was lower (p < 0.05) than that of SL ewes. The concentrations of β-hydroxybutyric acid (BHBA), non-esterified fatty acids (NEFA), interleukin-2 (IL-2), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) in the PL ewes were higher (p < 0.05), while the glucose (Glu), triglyceride (TG), total cholesterol (TC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC) values were lower (p < 0.05) than those of the SL ewes. ANOSIM analysis showed that the rumen bacterial structure of the SL, TL, and PL ewes was different on days Q21 and Q7. The relative abundance of Firmicutes and Bacteroidota in the rumen was affected (p < 0.05) by the number of fetuses: the relative abundance of Firmicutes (Ruminococcus, Butyrivibrio, Christensenellaceae_R-7_group, Lachnospiraceae_AC2044_group, Lachnospiraceae_XPB1014_group, and Anaeroplasma) was higher (p < 0.05), while that of Bacteroidota (Prevotella, Prevotellaceae_UCG-003, and Prevotellaceae_UCG-001) was lower (p < 0.05) in the SL ewes than in the PL ewes. In summary, the rumen microbial structure and energy metabolites of ewes in late gestation with different numbers of fetuses were different. Triplet-fetal ewes were characterized by lower BCS and antioxidant capacity and were prone to the triggering of inflammatory responses.

This paper considers the problem of tracking a three-dimensional target under the condition that only a single two-dimensional radar is available. Since a two-dimensional radar can only measure the slant range and azimuth information relative to the target, an unobservability issue arises in this tracking application. Therefore, we first investigate the observability issue of tracking a three-dimensional target with a single two-dimensional radar from two perspectives, including intuitive illustration and quantitative analysis. From the perspective of intuitive illustration, we demonstrate “What is the unobservability issue” and “How does the relative target-radar geometry influence the observability of the tracking system”. From the perspective of quantitative analysis, we construct a novel observability metric for this special tracking problem. Second, aiming at improving tracking performance under the unobservability of target height, we propose an observability-based Gaussian sum cubature Kalman filter. Built within the Gaussian sum framework and based on the height-parameterized strategy, this novel algorithm uses a set of independent fifth-degree cubature Kalman filters, each of which can detect the system observability variation and enhance the tracking accuracy by using a Gaussian splitting scheme under low-degree observability. Finally, the effectiveness of the presented filtering algorithm is validated through lots of simulation experiments.

Hyperspectral image (HSI) classification is a crucial technique that assigns each pixel in an image to a specific land cover category by leveraging both spectral and spatial information. In recent years, HSI classification methods based on convolutional neural networks (CNNs) and Transformers have significantly improved performance due to their strong feature extraction capabilities. However, these improvements often come with increased model complexity, leading to higher computational costs. To address this, we propose a compact and efficient spectral-spatial feature extraction and attention-based neural network (SSFAN) for HSI classification. The SSFAN model consists of three core modules: the Parallel Spectral-Spatial Feature Extraction Block (PSSB), the Scan Block, and the Squeeze-and-Excitation MLP Block (SEMB). After preprocessing the HSI data, it is fed into the PSSB module, which contains two parallel streams, each comprising a 3D convolutional layer and a 2D convolutional layer. The 3D convolutional layer extracts spectral and spatial features from the input hyperspectral data, while the 2D convolutional layer further enhances the spatial feature representation. Next, the Scan Block module employs a layered scanning strategy to extract spatial information at different scales from the central pixel outward, enabling the model to capture both local and global spatial relationships. The SEMB module combines the Spectral-Spatial Recurrent Block (SSRB) and the MLP Block. The SSRB, with its adaptive weight assignment mechanism in the SToken Module, flexibly handles time steps and feature dimensions, performing deep spectral and spatial feature extraction through multiple state updates. Finally, the MLP Block processes the input features through a series of linear transformations, GELU activation functions, and Dropout layers, capturing complex patterns and relationships within the data, and concludes with an argmax layer for classification. Experimental results show that the proposed SSFAN model delivers superior classification performance, outperforming the second-best method by 1.72%, 5.19%, and 1.94% in OA, AA, and Kappa coefficient, respectively, on the Indian Pines dataset. Additionally, it requires less training and testing time compared to other state-of-the-art deep learning methods.

Abstract N‐methyladenosine (m6A) represents a prevalent RNA modification observed in colorectal cancer. Despite its abundance, the biological implications of m6A methylation on the lncRNA CARMN remain elusive in colorectal cancer, especially for mutant p53 gain‐of‐function. Here, we elucidate that CARMN exhibits diminished expression levels in colorectal cancer patients with mutant p53, attributed to its rich m6A methylation, which promotes cancer proliferation, invasion and metastasis in vitro and in vivo. Further investigation illustrates that ALKBH5 acts as a direct demethylase of CARMN, targeting 477 methylation sites, thereby preserving CARMN expression. However, the interaction of mutant p53 with the ALKBH5 promoter impedes its transcription, enhancing m6A methylation levels on CARMN. Subsequently, YTHDF2/YTHDF3 recognise and degrade m6A‐modified CARMN. Concurrently, overexpressing CARMN significantly suppressed colorectal cancer progression in vitro and in vivo. Additionally, miR‐5683 was identified as a direct downstream target of lncRNA CARMN, exerting an antitumour effect by cooperatively downregulating FGF2 expression. Our findings revealed the regulator and functional mechanism of CARMN in colorectal cancer with mutant p53, potentially offering insights into demethylation‐based strategies for cancer diagnosis and therapy. The m6A methylation of CARMN that is prime for mutant p53 gain‐of‐function‐induced malignant progression of colorectal cancer, identifying a promising approach for cancer therapy.

For addressing the limitations of traditional elastic metamaterials in opening wide bandgaps below 100 Hz, a tunable pneumatic metamaterial plate with airbag local resonators is proposed. Utilizing the characteristics of airbags, such as small volume, large load-bearing capacity, easy stiffness adjustment, and the ability to provide multi-directional restoring forces, a structured low-stiffness local resonator with a certain load-bearing capacity is designed. By varying the gauge pressure of the airbag, the bandgap can be moved toward lower frequencies, thereby achieving a broad low-frequency vibration suppression capability for various wave propagations. The low-frequency vibration bandgap characteristics of the tunable pneumatic metamaterial are analyzed and verified by applying the finite element method. The results illustrate that this tunable pneumatic metamaterial can attenuate bending waves in the range of 22–121 Hz by adjusting the air pressure. Moreover, increasing the gauge pressure will not only shift the complete bandgap toward lower frequencies but also significantly expand the bandwidth of the complete bandgap. For instance, increasing the gauge pressure from 0 to 50 kPa reduces the opening frequency of the complete bandgap from 36 to 22 Hz while enhancing the relative bandwidth from 0.52 to 0.85. Extending from this, a parametric study was conducted to examine the impact of the structural parameters of airbag-type resonant units on bandgap evolution, summarizing the general principles for achieving wide low-frequency bandgaps. Finally, the bandgap characteristics of the tunable pneumatic metamaterial are confirmed through the frequency response function of a finite periodic structure.

Developing non-platinum group metal (non-PGM) electrocatalysts for the oxygen reduction reaction (ORR) is a critical effort toward low-cost fuel cells and metal–air batteries. Such catalysts require a uniform dispersion of metal atoms on a solid support, typically consisting of nitrogen doped carbon. However, the synthesis of non-PGM electrocatalysts is often complex, and metal loadings are typically below 10 wt. %, limiting the number of active sites and, therefore, the catalytic activity. In this work, we overcome these limits by synthesizing tandem supported, copper loaded electrocatalysts. Through one-pot pyrolysis, we make carbon black/Cu-doped graphitic carbon nitride (g-C3N4) core–shell structures to optimize the trade-off between conductivity and metal-loading capacity and achieve a Cu loading larger than 20 wt. %. By controlling the pyrolysis temperature, we systematically modulate the catalyst composition, structure, electrocatalytic activity, and stability. At a low pyrolysis temperature of only 600 °C, we achieve an onset potential of 0.90 V and a half-wave potential of 0.81 V vs RHE for alkaline ORR and negligible current loss after 10 000 potential cycles. These results demonstrate an effective approach to realize non-PGM electrocatalysts with optimum metal-loading, activity, and stability, thus unlocking their potential for real-world applications.

One of the primary contributors to automobile exhaust pollution is the significant deviation between the actual and theoretical air-fuel ratios during transient conditions, leading to a decrease in the conversion efficiency of three-way catalytic converters. Therefore, it becomes imperative to enhance fuel economy, reduce pollutant emissions, and improve the accuracy of transient control over air-fuel ratio (AFR) in order to mitigate automobile exhaust pollution. In this study, we propose a Linear Active Disturbance Rejection Control (LADRC) Hydrogen Doping Compensation Controller (HDC) to achieve precise control over the acceleration transient AFR of gasoline engines. By analyzing the dynamic effects of oil film and its impact on AFR, we establish a dynamic effect model for oil film and utilize hydrogen's exceptional auxiliary combustion characteristics as compensation for fuel loss. Comparative experimental results demonstrate that our proposed algorithm can rapidly regulate the AFR close to its ideal value under three different transient conditions while exhibiting superior anti-interference capability and effectively enhancing fuel economy.

Solar wind charge exchange (SWCX) is the process of solar wind high-valence ions exchanging charges with neutral components and generating soft X-rays. Recently, detecting the SWCX emission from the magnetosphere is proposed as a new technique to study the magnetosphere using panoramic soft X-ray imaging. To better prepare for the data analysis of upcoming magnetospheric soft X-ray imaging missions, this paper compares the magnetospheric SWCX emission obtained by two methods in an XMM-Newton observation, during which the solar wind changed dramatically. The two methods differ in the data used to fit the diffuse X-ray background (DXB) parameters in spectral analysis. The method adding data from the ROSAT All-Sky Survey (RASS) is called the RASS method. The method using the quiet observation data is called the Quiet method, where quiet observations usually refer to observations made by the same satellite with the same target but under weaker solar wind conditions. Results show that the spectral compositions of magnetospheric SWCX emission obtained by the two methods are very similar, and the changes in intensity over time are highly consistent, although the intensity obtained by the RASS method is about \begin{document}$2.68\,\pm\, 0.56$\end{document} keV \begin{document}${\rm{cm}}^{-2} {\rm{s}}^{-1} {\rm{sr}}^{-1}$\end{document} higher than that obtained by the Quiet method. Since the DXB intensity obtained by the RASS method is about \begin{document}$2.84\,\pm\, 0.74$\end{document} keV \begin{document}${\rm{ cm}}^{-2} {\rm{s}}^{-1} {\rm{sr}}^{-1}$\end{document} lower than that obtained by the Quiet method, and the linear correlation coefficient between the difference of SWCX and DXB obtained by the two methods in different energy band is close to −1, the differences in magnetospheric SWCX can be fully attributed to the differences in the fitted DXB. The difference between the two methods is most significant when the energy is less than 0.7 keV, which is also the main energy band of SWCX emission. In addition, the difference between the two methods is not related to the SWCX intensity and, to some extent, to solar wind conditions, because SWCX intensity typically varies with the solar wind. In summary, both methods are robust and reliable, and should be considered based on the best available options.

Abstract External cycling regenerating nitrogen oxides (NOx ≡ NO + NO2) from their oxidative reservoir, NOz, is proposed to reshape the temporal–spatial distribution of NOx and consequently hydroxyl radical (OH), the most important oxidant in the atmosphere. Here we verify the in situ external cycling of NOx in various environments with nitrous acid (HONO) as an intermediate based on synthesized field evidence collected onboard aircraft platform at daytime. External cycling helps to reconcile stubborn underestimation on observed ratios of HONO/NO2 and NO2/NOz by current chemical model schemes and rationalize atypical diurnal concentration profiles of HONO and NO2 lacking noontime valleys specially observed in low-NOx atmospheres. Perturbation on the budget of HONO and NOx by external cycling is also found to increase as NOx concentration decreases. Consequently, model underestimation of OH observations by up to 41% in low NOx atmospheres is attributed to the omission of external cycling in models.

Abstract Ferroptosis is a new type of iron-dependent programmed cell death induced by lipid peroxidation. However, the underlying mechanisms and function in tumor therapy still remain undisclosed especially in post-transcription regulation. Here, we found that targeting AKT significantly induced GPX4 dependent ferroptosis and suppressed colorectal cancer growth both in vitro and in vivo. During this process, demethylase FTO was downregulated, which increased the m6A methylation level of GPX4, subsequently recognized by YTHDF2 and degraded. Prediction results showed that there are three potential methylated sites (193/647/766), and 193 site was identified as the right one, which was demethylated by FTO and read by YTHDF2. In parallel, AKT inhibition caused the accumulation of ROS which had a negative feedback on GPX4 expression. In addition, protective autophagy was initiated by MK2206 stimulation, while blocking autophagy further increased ferroptosis and markedly enhanced the anti-tumor activity of MK2206. In a word, inhibiting AKT activated ferroptosis through FTO/YTHDF2/GPX4 axis to suppress colon cancer progression, which raised FTO/GPX4 as potential biomarkers and targets in colorectal cancer therapy.

Abstract To investigate the molecular mechanism of Yiwei Decoction (YWD) in preventing Premature ovarian insufficiency (POI)-related osteoporosis from the hypothalamic perspective , and to screen for the key active and acting molecules in YWD. Cyclophosphamide was used to create the POI rat model. Groups A, B, and C were established. The Model + YWD group was group A, the model control group was group B, and the normal control group was group C. ELISA was used to determine serum GnRH and FSH levels after gavage. The transcription levels of mRNAs in each group's hypothalamus tissues were examined using RNA-seq sequencing technology. The GSEA method was used to enrich pathways based on the gene expression levels of each group. The TCM–active ingredient–target–disease network map was created using differentially expressed mRNAs (DEmRNAs) and network pharmacology. The molecular docking method was employed to investigate the affinity of the active ingredient with key targets. GnRH and FSH levels in POI rats' serum were reduced by YWD. Between groups A and B, there were 638 DEmRNAs (P

We propose a cotton pest and disease recognition method, SpemNet, based on efficient multi-scale attention and stacking patch embedding. By introducing the SPE module and the EMA module, we successfully solve the problems of local feature learning difficulty and insufficient multi-scale feature integration in the traditional Vision Transformer model, which significantly improve the performance and efficiency of the model. In our experiments, we comprehensively validate the SpemNet model on the CottonInsect dataset, and the results show that SpemNet performs well in the cotton pest recognition task, with significant effectiveness and superiority. The SpemNet model excels in key metrics such as precision and F1 score, demonstrating significant potential and superiority in the cotton pest and disease recognition task. This study provides an efficient and reliable solution in the field of cotton pest and disease identification, which is of great theoretical and applied significance.

Aerial-aquatic unmanned vehicles are a combination of unmanned aerial vehicles and unmanned submersibles, capable of conducting patrols in both the air and underwater domains. This article introduces a novel aerial-aquatic unmanned vehicle that integrates fixed-wing configuration and flapping-wing configuration. In order to improve the low efficiency of the classic diagonal motion trajectory, this paper proposed an improved diagonal motion trajectory based on joint optimization of the stroke angle and angle of attack curve. The proposed method has been verified through simulations and experiments. A prototype was developed and experiments were completed, both indoors and outdoors, wherein the system’s transmedium transition capability and flapping propulsion performance were comprehensively validated. Additionally, utilizing flapping propulsion, an average underwater propulsion speed of 0.92 m/s was achieved.

Changes in physiological and biochemical parameters are crucial for the reproductive performance and health of perinatal ewes. This study investigated the temporal variations in feed intake, nutrient digestibility, serum parameters, and ruminal fermentation on days 21, 14, and 7 before lambing (Q21, Q14, and Q7) and days 3, 7, and 14 after lambing (H3, H7, and H14). The results showed that dry matter intake (DMI) and glucose (Glu) gradually decreased (p < 0.05) before lambing and increased (p < 0.05) after lambing. The digestibility of dry matter (DMD), crude protein (CPD), and acid detergent fiber (ADFD) increased (p < 0.05) before lambing, then decreased (p < 0.05) on day H3, and then increased (p < 0.05) on day H14. The rumen pH, NH3-N, and triglycerides (TG) gradually increased (p < 0.05) before lambing and were higher (p < 0.05) on day Q7 than after lambing. The concentrations of acetate, butyrate, and total volatile fatty acids (T-VFA) were lower (p < 0.05) on day Q7 than those on days Q21 and Q14, then increased (p < 0.05) after lambing. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) concentrations gradually decreased (p < 0.05) in perinatal ewes. BHBA and NEFA concentrations were lower (p < 0.05) on day Q21 than those from days Q14 to H14. The rumen microbiota compositions were different (p < 0.05) in perinatal ewes, and g_Anaerovibrio, g_Lachnobacterium, and g_Schwartzia were positively correlated (p < 0.05) with DMI, Glu, acetate, propionate, and T-VFA, and negatively correlated (p < 0.05) with LDL-C. g_Bacillus was negatively correlated (p < 0.05) with DMI, Glu, acetate, propionate, butyrate, and T-VFA, but positively correlated (p < 0.05) with rumen pH and LDL-C. In summary, the DMI, nutrient digestibility, rumen fermentation, and serum parameters changed during the perinatal period of ewes, and the changes in DMI, serum glucose, acetate, propionate, and T-VFA were related to the rumen bacteria.

The coupling between solar wind and the magnetosphere and the dynamic processes in geo-space are the basic driving factors of space weather. Understanding these processes on the system level is essential to the studies of space physics and space weather. Recent solar wind charge exchange (SWCX) X-ray emission discoveries provide a novel approach to detect the large-scale magnetosphere through soft X-ray imaging. SWCX occurs when high-charge heavy ions such as C6+, N7+, O7+, and O8+ in the solar wind interact with neutral atoms or molecules, such as neutral hydrogen atoms in near-Earth space, neutral hydrogen and helium atoms in the heliosphere, and H2O and CO2 molecules on comets and other planets. Solar wind ions become excited by receiving one or more electrons, and then return to the ground state by releasing one or more photons in the soft X-ray band. The characteristics of the SWCX emissions include the X-ray spectrum showing line emissions corresponding to different species of solar wind particles and neutrons, and fast time variations closely related to solar wind variations. The SWCX soft X-ray emission of the Earth's magnetosphere mainly occurs in the magnetosheath on the dayside and the cusp regions. Therefore, the magnetosphere can be remotely imaged using large-scale soft X-ray imaging technology, allowing the fundamental modes of the interaction between the solar wind and magnetosphere to be recognized on a systematic scale.In this context, the European Space Agency (ESA) and Chinese Academy of Sciences (CAS) jointly proposed the Solar wind Magnetosphere Ionosphere Link Explorer (SMILE). SMILE was approved in 2016 and implemented thereafter. SMILE aims to provide remote sensing measurements of the magnetopause and bow shock around the subsolar region, part of the cusp regions, and the aurora, as well as simultaneous in situ observations of the solar wind plasma and magnetic field. SMILE is planned to be launched in 2024–2025. Other missions have also been proposed to image the Earth's magnetosphere, such as the GEOspace X-ray imager (GEO-X) in Japan, Lunar Environment heliospherics X-ray Imager (LEXI) in the United States, and Lunar-based soft X-ray imager (LSXI) in China.With the advent of soft X-ray imaging missions to detect the magnetopause, evaluating the expected soft X-ray images and developing appropriate techniques to extract 3-dimentional boundary information from the 2-dimentional images is essential. Global magnetohydrodynamic (MHD) and instrument simulations are used to generate expected X-ray images under different solar wind conditions with different viewing geometries. Based on these images, several approaches have been developed to analyze the signals, composing the 'arsenal' or 'toolkit' for magnetopause reconstruction. Each approach has its own advantages and disadvantages, applicable to different situations.This paper introduces the mechanism of magnetospheric X-ray emission, reviews the research on the observational evidence and characteristics of SWCX X-ray emissions, summarizes the progress of simulation studies, presents the missions (or concept) of the magnetospheric X-ray detection, and discusses the possibility of future implementation of X-ray imaging for detecting other planets.

To explore the hydraulic coupling characteristics of rocks, triaxial compression tests on water-saturated sandstone under hydro-mechanical coupling were carried out using the MTS815 rock mechanics test system. The test confining pressures were 10, 20, 30 MPa. Under each confining pressure, according to the ratio of pore water pressure to confining pressure, the pore water pressure was set to seven levels, which are 0, 10%、20%、40%、60%、80% and 90%. Then, the influence of the confining pressure and pore water pressure on the mechanical parameters such as the elastic modulus and Poisson’s ratio of the sandstone was analyzed. The energy evolution characteristics of sandstone under hydro-mechanical coupling were discussed in terms of energy curves, characteristic energy parameters and energy change ratios. Finally, the variation patterns of peak and residual strength were analyzed and the applicability of the Mohr-Coulomb and Hoek-Brown criteria under hydro-mechanical coupling was discussed based on the effective stresses. The results show that: ① the peak strength, residual strength, and elastic modulus of water-saturated sandstone increase with the increase of confining pressure, and decrease with increasing pore water pressure. Poisson’s ratio decreases as the confining pressure increases and increases as the pore water pressure increases. ② Under hydro-mechanical coupling, sandstone mainly undergoes shear failure, and as the pore water pressure increases, hydraulic fracturing is significant and its damage becomes more intense. ③ Combined with the test data of the sandstone and the published literatures, the normalized strength attenuation equation of rock peak strength and residual strength under hydro-mechanical coupling is obtained with the ratio of pore water pressure to confining pressure as the characteristic parameter. The strength attenuation coefficient of rock residual strength is greater than that of peak strength. ④ The trend of energy evolution curves of sandstone is consistent, and its energy storage limitation, peak dissipated energy density and residual elastic energy density are positively correlated with confining pressure, and negatively correlated with pore water pressure. ⑤ The evolution law of peak strength and residual strength of rock under hydro-mechanical coupling are in accordance with the Mohr-Coulomb criterion and Hoek-Brown criterion. The effective internal friction angles corresponding to peak and residual rock strengths are less different, while the effective cohesion and Hoek-Brown criterion parameters corresponding to the peak strength are much greater than those corresponding to the residual strength.

A patient presenting with several basal cell carcinomas, pigmented nevi, and developmental defects was diagnosed with nevoid basal cell carcinoma syndrome. Gene panel sequencing and Sanger sequencing were used to identify a novel heterozygous frameshift mutation, c.1312dupA:p.Ser438Lysfs, in exon 9 of PTCH1. I-Tasser and PyMol analyses indicated that the mutated protein patched homolog 1 (PTCH1) lacked 12 transmembrane domains and the intracellular and extracellular rings of ECD2 compared with the wild-type protein, resulting in a remarkably different structure from that of the wild-type protein. This case extends our knowledge of the mutation spectrum of NBCCS.

Crop production is strongly impacted by soil nitrogen supply, which is regulated by soil micro-food webs consisting of nematodes, protists, fungi and bacteria. However, responses of soil micro-food webs to fertilization at the aggregate scale and their relationships with soil nitrogen supply and crop yield remain unclear. To address these knowledge gaps, we investigated soils subjected to typical fertilization treatments in a long-term field experiment, which included: no fertilizer control (CK); synthetic fertilizers (NPK); partial synthetic nitrogen replacement with pig slurry (OMNPK) or crop straw (RSDNPK) and incorporating biochar with synthetic fertilizers (BCNPK). The composition of different biological groups was changed significantly by fertilization, with bacteria under RSDNPK being more responsive than other groups. The co-occurrence network of the soil micro-food web had more edges in microaggregates than those in large and small macroaggregates due to the significantly higher nodal degree of bacteria and fungi. On average, 76 % of the topologically important (TI) taxa in the networks were bacteria. In modules where nematodes and protists were present, 8 %-100 % of them were attributed to TI taxa while the ratio for bacteria was 3 %-7 %. Specific assemblages of functionally important (FI) taxa covering all tested biological groups at the aggregate scale were positively associated with soil labile nitrogen, related enzymes and crop yield. Random forest regression further indicates the high importance of these FI taxa to crop yield. However, less than 20 % of them were attributed to TI taxa of the networks. In summary, distinct assemblages of taxa covering multiple trophic levels regulate network topology and soil nitrogen supply + crop yield, which provides insights for targeted manipulation of soil micro-food webs through knowledge-based fertilization to harness the biological potential of cropland soils.

Acoustic emission is a promising candidate among online process monitoring methods in laser powder bed fusion. Although previous studies have demonstrated the feasibility for acoustic-based monitoring, an underlying understanding of the acoustic specialities related to laser–powder interactions in the enclosed chamber is scarce. This research employed a microphone to collect the acoustic emission signal during laser printing processes. Two contents are contained in the raw data: static pressure variation and acoustic signal. The features of each content are investigated and it follows several significant findings. First, more violent fluctuations of ambient gas static pressure in the chamber are due to the high temperature gradient of ambient gas and recoil pressure over the laser-material interaction zone, which typically occurs in a very low frequency band (10 kHz). For powder bed additive manufacturing, these results offer a guidance for signal processing and machine learning to dig out the signal signatures of a specific defect in terms of acoustic monitoring.

The rapid growth of electronic devices, electric vehicles, and mobile energy storage has produced large quantities of spent batteries, leading to significant environmental issues and a shortage of lithium resources. Recycling spent batteries has become urgent to protect the environment. The key to treating spent lithium-ion batteries is to implement green and efficient regeneration. This study proposes a recycling method for the direct regeneration of spent lithium iron phosphate (LFP) batteries using hydrothermal reduction. Ascorbic acid (AA) was used as a low-cost and environmentally friendly reductant to reduce Fe3+ in spent LiFePO4. We also investigated the role of AA in the hydrothermal process and its effects on the electrochemical properties of the regenerated LiFePO4 cathode material (AA-SR-LFP). The results showed that the hydrothermal reduction direct regeneration method successfully produced AA-SR-LFP with good crystallinity and electrochemical properties. AA-SR-LFP exhibited excellent electrochemical properties, with an initial discharge specific capacity of 144.4 mAh g−1 at 1 C and a capacity retention rate of 98.6% after 100 cycles. In summary, the hydrothermal reduction direct regeneration method effectively repairs the defects in the chemical composition and crystal structure of spent LiFePO4. It can be regarded as a green and effective regeneration approach for spent LiFePO4 cathode materials.

Considering the frequently large price fluctuations for soybean meal, an alternative is the increased use of locally produced high-protein ingredients. The objective of this study was to evaluate the effects of the total replacement of soybean meal with different sources of protein on the growth performance, nutrient digestibility, serum parameters, rumen fermentation parameters, and bacterial communities in growing lambs. Sixty sheep with similar body weights (38.46 ± 0.71 kg) were distributed to one of five treatments: soybean meal (SBM); cottonseed meal (COM); peanut meal (PEM); rapeseed meal (RAM); and distillers’ dried grains with solubles (DDGS). The experiment lasted 62 days with a 10-day adaptation period and a 52-day growing period. The results indicated that the body weight and average daily gain were not affected by different protein sources (p > 0.05), but the dry matter intake of the SBM group was lower than that of the other groups (p < 0.05); otherwise, the feed efficiency was higher (p < 0.05). The digestion of dry matter was higher in the SBM, COM, and RAM groups than in the DDGS and PEM groups (p < 0.05). Meanwhile, compared to the other groups, the SBM group had the highest digestion of gross energy and crude protein (p < 0.05). In addition, the concentration of glutathione peroxidase was highest in the SBM group (p < 0.05). Regarding the rumen fermentation, the SBM group had the highest concentration of NH3-N (p < 0.05). The rumen bacterial community was not affected by treatments (p > 0.05). In conclusion, the total replacement of soybean meal with cottonseed, peanut, rapeseed, or DDGS reduced digestibility but did not impact the body weight or average daily gain of growing lambs and had no effect on the immune function and rumen bacterial community; thus, they can be used to substitute the soybean meal.

Yanshan Cashmere bucks are seasonal breeding animals and an important national genetic resource. This study aimed to investigate the involvement of prolactin (PRL) in the epididymal function of bucks. Twenty eleven-month-old Cashmere bucks were randomly divided into a control (CON) group and a bromocriptine (BCR, a prolactin inhibitor, 0.06 mg/kg body weight (BW)) treatment group. The experiment was conducted from September to October 2020 in Qinhuangdao City, China, and lasted for 30 days. Blood was collected on the last day before the BCR treatment (day 0) and on the 15th and 30th days after the BCR treatment (days 15 and 30). On the 30th day, all bucks were transported to the local slaughterhouse, where epididymal samples were collected immediately after slaughter. The left epididymis was preserved in 4% paraformaldehyde for histological observation, and the right epididymis was immediately preserved in liquid nitrogen for RNA sequencing (RNA-seq). The results show that the PRL inhibitor reduced the serum PRL and estradiol (E2) concentrations (p < 0.05) and tended to decrease luteinizing hormone (LH) concentrations (p = 0.052) by the 30th day, but no differences (p > 0.05) occurred by either day 0 or 15. There were no differences (p > 0.05) observed in the follicle-stimulating hormone (FSH), testosterone (T), and dihydrotestosterone (DHT) concentrations between the two groups. The PRL receptor (PRLR) protein was mainly located in the cytoplasm and intercellular substance of the epididymal epithelial cells. The PRL inhibitor decreased (p < 0.05) the expression of the PRLR protein in the epididymis. In the BCR group, the height of the epididymal epithelium in the caput and cauda increased, as did the diameter of the epididymal duct in the caput (p < 0.05). However, the diameter of the cauda epididymal duct decreased (p < 0.05). Thereafter, a total of 358 differentially expressed genes (DEGs) were identified in the epididymal tissues, among which 191 were upregulated and 167 were downregulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that ESR2, MAPK10, JUN, ACTL7A, and CALML4 were mainly enriched in the estrogen signaling pathway, steroid binding, calcium ion binding, the GnRH signaling pathway, the cAMP signaling pathway, and the chemical carcinogenesis–reactive oxygen species pathway, which are related to epididymal function. In conclusion, the inhibition of PRL may affect the structure of the epididymis by reducing the expression of the PRLR protein and the secretion of E2. ESR2, MAPK10, JUN, ACTL7A, and CALML4 could be the key genes of PRL in its regulation of epididymal reproductive function.

Although deep learning has been proven to significantly outperform most traditional methods in the classification of large-scale balanced image datasets, collecting enough samples for defect classification is extremely time-consuming and costly. In this paper, we propose a lightweight defect classification method based on few-shot image generation and self-attention fused convolution features. We constructed a 4-class dataset using welding seam images collected from a solar cell module packaging production line. To address the issue of limited defect samples, especially for classes with less than 10 images, we implemented two strategies. Geometric enhancement techniques were first used to extend the defective images. Secondly, multi-scale feature fusion Generative Adversarial Networks (GANs) were utilized to further enhance the dataset. We then performed the feature-level fusion of convolution neural networks and self-attention networks, achieving a classification accuracy of 98.19%. Our experimental results demonstrate that the proposed model performs well in small sample defect classification tasks. And, it can be effectively applied to product quality inspection tasks in industrial production lines.

Prolactin (PRL) plays an important role in animal follicle development and ovulation. However, its regulatory effects on the different stages of the estrus cycle in ewes are unclear. In this study, bromocriptine (BCR, PRL inhibitor) was used to study the effect of PRL on the secretion of reproductive hormones and gene expressions in order to explore its regulatory effects on the sexual cycle of ewes. Eighty healthy ewes with the same parity and similar weights were randomly assigned to the control group (C, n = 40) and the treatment group (T, n = 40, fed bromocriptine). After estrus synchronization, thirty-one ewes with overt signs of estrus were selected from each group. Six blood samples were randomly obtained by jugular venipuncture to measure the concentration of PRL, estrogen (E2), progesterone (P4), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and gonadotropin-releasing hormone (GnRH) in the proestrus, estrus, metestrus, and diestrus. At the same time, we collected the ovaries of the six ewes in vivo after anesthesia in order to detect follicle and corpus luteum (CL) counts and measure the expression of hormone-receptor and apoptosis-related genes. The results show that PRL inhibition had no significant effects on the length of the estrus cycle (p > 0.05). In proestrus, the number of large and small follicles, the levels of E2, FSH, and GnRH, and the expressions of ER, FSHR, and the apoptotic gene Caspase-3 were increased (p < 0.05); and the number of middle follicles and the expression of anti-apoptotic gene Bcl-2 were decreased (p < 0.05) in the T group. In estrus, the number of large follicles, the levels of E2 and GnRH, and the expressions of the StAR, CYP19A1, and Bcl-2 genes were increased (p < 0.05), and the number of middle follicles was decreased (p < 0.05) in the T group. In metestrus, the number of small follicles and the expression of LHR (p < 0.05) and the pro-apoptotic gene Bax were increased (p < 0.05); the number of middle follicles was decreased (p < 0.05) in the T group. In diestrus, the number of large follicles, middle follicles, and CL, the level of P4, and the expressions of PR, 3β-HSD, StAR, Caspase-3, and Bax were increased (p < 0.05); the number of small follicles and the expression of Bcl-2 were decreased (p < 0.05) in the T group. In summary, PRL inhibition can affect the secretion of reproductive hormones, the follicle count, and the gene expression during the estrus cycle. These results provide a basis for understanding the mechanisms underlying the regulation of the ewe estrus cycle by PRL.

In the field of biomedicine, efficiently and non-invasively isolating target cells has always been one of the core challenges. Optical fiber tweezers offer precise and non-invasive manipulation of cells within a medium and can be easily integrated with microfluidic systems. Therefore, this paper investigated the mechanism of cell manipulation using scattering force with optical fiber tweezers. We employed flat-ended single-mode fiber to drive and sort cells and derived the corresponding scattering force formula based on the T-matrix model. A single-mode optical tweezers system for cell sorting was developed, and an optofluidic experimental platform was constructed that effectively integrates the optical system with microfluidic chips. The chip, featuring an expanded cross-channel design, successfully achieved continuous separation of yeast cells (8~10 µm in diameter) and polystyrene microspheres (15~20 µm in diameter), with a sorting efficiency of up to 86% and maintaining viability in approximately 90% of the yeast cells. Compared to other sorting systems, this system does not require labeling and can achieve continuous sorting with cell viability at a lower cost of instrumentation.

IntroductionThis study aimed to investigate the digestive function, urea utilization ability, and bacterial composition changes in rumen microbiota under high urea (5% urea in diet) over 23 days of continuous batch culture in vitro.MethodsThe gas production, dry matter digestibility, and bacterial counts were determined for the continuously batch-cultured rumen fluid (CRF). The changes in fermentation parameters, NH3-N utilization efficiency, and microbial taxa were analyzed in CRF and were compared with that of fresh rumen fluid (RF), frozen rumen fluid (FRF, frozen rumen fluid at −80°C for 1 month), and the mixed rumen fluid (MRF, 3/4 RF mixed with 1/4 CRF) with in vitro rumen fermentation.ResultsThe results showed that the dry matter digestibility remained stable while both the microbial counts and diversity significantly decreased over the 23 days of continuous batch culture. However, the NH3-N utilization efficiency of the CRF group was significantly higher than that of RF, FRF, and MRF groups (p