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Abstract Background Trihliex transcription factors (TFs) play crucial roles in plant growth and development, stress response, and plant hormone signaling network transmission. In order to comprehensively investigate the functions of trihliex genes in eggplant development and the abiotic stress response, we conducted an extensive analysis of the trihliex gene family in the eggplant genome. Results In this study, 30 trihelix gene family members were unevenly distributed on 12 chromosomes. On the basis of their phylogenetic relationships, these genes were conserved in different plant species and could be divided into six subfamilies, with trihelix genes within the same subfamily sharing similar structures. The promoter regions of trihelix genes contained cis-acting elements related to plant growth and development, plant hormones, and abiotic stress responses, suggesting potential applications in the development of more resistant crops. Selective pressure assessments indicated that trihliex genes have undergone purifying selection pressure. Expression analysis on the basis of transcriptomic profiles revealed that SmGT18, SmGT29, SmGT6, and SmGT28 are highly expressed in roots, leaves, flowers, and fruits, respectively. Expression analysis via quantitative real-time PCR (qRT‒PCR) revealed that most trihelix genes respond to low temperature, abscisic acid (ABA), and salicylic acid (SA), with SmGT29 exhibiting significant upregulation under cold stress conditions. The SmGT29 gene was subsequently successfully cloned from eggplant, which was located in the nucleus, robust transcriptional activity, and a protein molecular weight of 74.59 kDa. On the basis of these findings, SmGT29 was postulated to be a pivotal candidate gene that actively responds to biotic stress stimuli, thereby supporting the plant’s innate stress resistance mechanisms. Conclusion In summary, this study was the first report on trihelix genes and their potential roles in eggplant plants. These results provided valuable insights for enhancing stress resistance and quality traits in eggplant breeding, thereby serving as a crucial reference for future improvement efforts.

Abstract Prostate cancer (PC) treatment, particularly androgen deprivation therapy (ADT), remains pivotal, albeit linked to increased fracture risk due to osteoporosis. The advent of novel hormonal agents (NHAs) has spurred inquiries into their influence on bone health. This study aimed to evaluate the impact of NHAs on bone health in patients receiving combination therapy. We conducted a retrospective analysis using Taiwan’s National Health Insurance Research Database, encompassing men aged 45 and above diagnosed with PC without bone metastasis and undergoing ADT between 2000 and 2018. The study involved 25,949 patients, categorized into those receiving standard ADT (n = 25,166) and those on NHA combination therapy (n = 783). Our analysis delved into fracture risk, comorbidities, and osteoporosis treatments. Patients on NHA combination therapy faced significantly higher risks of any osteoporotic fracture and major osteoporotic fracture than those on ADT alone (HR = 1.29, 95% CI 1.04–1.61; HR = 1.37, 95% CI 1.06–1.75, respectively). Notably, age emerged as a critical factor, with the highest risk observed in those aged 90 or above. The 5-year overall survival rates were lower for patients who experienced any osteoporotic fracture, major osteoporotic fracture, and hospitalization due to osteoporotic fracture compared to those who did not experience these fractures (51.5% vs. 56.5%, 47.1% vs. 56.7%, and 48.2% vs. 56.3%, respectively, p

Abstract Lupus nephritis (LN) is a prevalent and severe manifestation of systemic lupus erythematosus (SLE), leading to significant morbidity and mortality. OTUB1, a deubiquitinating enzyme, has emerged as a potential therapeutic target due to its role in cellular protection and regulation of ferroptosis, a form of cell death linked to LN. Our study revealed significantly reduced OTUB1 expression in the glomeruli of LN patients and podocytes, correlated with disease severity. CRISPR/Cas9-mediated OTUB1 knockout in podocytes resulted in pronounced injury, indicated by decreased levels of nephrin and podocin. Ferrostatin-1 treatment effectively mitigated this injury, restoring SLC7A11 expression and significantly reducing MDA levels, Fe2+ levels, BODIPY C11 expression, and normalized cysteine and glutathione expression. In the MRL/lpr mouse model, Ferrostatin-1 significantly improved renal function decreased proteinuria, and ameliorated renal histopathological changes, including reduced glomerular endothelial swelling, mesangial cell proliferation, and leukocyte infiltration. These results underscore the protective role of Ferrostatin-1 in modulating the pathogenesis of LN. OTUB1 plays a crucial protective role against podocyte injury in LN by regulating ferroptosis. Ferrostatin-1 effectively mitigates podocyte damage induced by OTUB1 deficiency, suggesting that targeting ferroptosis could be a promising therapeutic strategy for LN.

Abstract Antibacterial bone cements (ABCs), such as antibiotic-loaded bone cements (ALBCs), have been widely utilized in clinical treatments. Currently, bone cements loaded with vancomycin, gentamicin, tobramycin, or clindamycin are approved by the US Food and Drug Administration. However, traditional ALBCs exhibit drawbacks like burst release and bacterial resistance. Therefore, there is a demand for the development of antibacterial bone cements containing novel agents to address these defects. In this review, we provide an overview and prospect of the new antibacterial agents that can be used or have the potential to be applied in bone cement, including metallic antibacterial agents, pH-switchable antibacterial agents, cationic polymers, N-halamines, non-leaching acrylic monomers, antimicrobial peptides and enzymes. Additionally, we have conducted a preliminary assessment of the feasibility of bone cement containing N-halamine, which has demonstrated good antibacterial activities. The conclusion of this review is that the research and utilization of bone cement containing novel antibacterial agents contribute to addressing the limitations of ALBCs. Therefore, it is necessary to continue expanding the research and use of bone cement incorporating novel antibacterial agents. This review offers a novel perspectives for designing ABCs and treating bone infections. Graphical abstract

Abstract Background The ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (NHHR) is a novel lipid measure for assessing the risk of cardiovascular disease. Lipid metabolism disorders are reportedly associated with hearing impairment. This study aimed to investigate the potential association between NHHR and hearing. Methods The data used in this study were obtained from the National Health and Nutrition Examination Survey (NHANES) cycles of 2005–2010 and 2017–2018, including 4,296 participants aged 6–19 years. The NHHR was calculated from lipid profiles, and hearing was assessed using pure-tone audiometry. Weighted multivariate logistic regression analyses were used to investigate the association between the NHHR and hearing loss. Subgroup and sensitivity analyses were performed to verify the robustness of the results. Results Univariate analysis revealed significant associations between the NHHR and hearing threshold at all categorized frequency (low, speech, or high-frequency) (P

Abstract Oxaliplatin is effective against colorectal cancer (CRC), but resistance hampers treatment. We found upregulated Dickkopf-1 (DKK1, a secreted protein) in oxaliplatin-resistant (OR) CRC cell lines and DKK1 levels increased by more than 2-fold in approximately 50% of oxaliplatin-resistant CRC tumors. DKK1 activates AKT via cytoskeleton-associated protein 4 (CKAP4, a DKK1 receptor), modulating oxaliplatin responses in vitro and in vivo. The leucine zipper (LZ) domain of CKAP4 and cysteine-rich domain 1 (CRD1) of secreted DKK1 are crucial for their interaction and AKT signaling. By utilizing the LZ protein, we disrupted DKK1 signaling, enhancing oxaliplatin sensitivity in OR CRC cells and xenograft tumors. This suggests that DKK1 as a chemoresistant factor in CRC via AKT activation. Targeting DKK1 with the LZ protein offers a promising therapeutic strategy for oxaliplatin-resistant CRC with high DKK1 levels. This study sheds light on oxaliplatin resistance mechanisms and proposes an innovative intervention for managing this challenge.

Abstract Background Bisphosphonate (BP) can treat osteoporosis and prevent osteoporotic fractures in clinical. However, the effect of BP on microstructure and mechanical properties of cortical and trabecular bone has been taken little attention, separately. Methods In this study, BP was used to intervene in ovariectomized female SD rats. The femoral micro-CT images were used to measure the structural parameters and reconstruct the 3D models in volume of interest. The structural parameters of cortical and trabecular bone were measured, and the mechanical properties were predicted using micro-finite element analysis. Results There was almost no significant difference in the morphological structure parameters and mechanical properties of cortical bone between normal, ovariectomized (sham-OVX) and BP intervention groups. However, BP could significantly improve bone volume fraction (BV/TV) and trabecular separation (Tb.SP) in inter-femoral condyles (IT) (sham-OVX vs. BP, p

Abstract Background Visceral adipose tissue in individuals with obesity is an independent cardiovascular risk indicator. However, it remains unclear whether adipose tissue influences common cardiovascular diseases, such as atherosclerosis, through its secreted exosomes. Methods The exosomes secreted by adipose tissue from diet-induced obesity mice were isolated to examine their impact on the progression of atherosclerosis and the associated mechanism. Endothelial apoptosis and the proliferation and migration of vascular smooth muscle cells (VSMCs) within the atherosclerotic plaque were evaluated. Statistical significance was analyzed using GraphPad Prism 9.0 with appropriate statistical tests. Results We demonstrate that adipose tissue-derived exosomes (AT-EX) exacerbate atherosclerosis progression by promoting endothelial apoptosis, proliferation, and migration of VSMCs within the plaque in vivo. MicroRNA-132/212 (miR-132/212) was detected within AT-EX cargo. Mechanistically, miR-132/212-enriched AT-EX exacerbates palmitate acid-induced endothelial apoptosis via targeting G protein subunit alpha 12 and enhances platelet-derived growth factor type BB-induced VSMC proliferation and migration by targeting phosphatase and tensin homolog in vitro. Importantly, melatonin decreases exosomal miR-132/212 levels, thereby mitigating the pro-atherosclerotic impact of AT-EX. Conclusion These data uncover the pathological mechanism by which adipose tissue-derived exosomes regulate the progression of atherosclerosis and identify miR-132/212 as potential diagnostic and therapeutic targets for atherosclerosis. Graphical Abstract

Abstract Ginsenoside Rb1 exhibits a wide range of biological activities, and gut microbiota is considered the main metabolic site for Rb1. However, the impact of gut microbiota on the pharmacokinetics of Rb1 are still uncertain. In this study, we investigated the gut microbiome changes and the pharmacokinetics after a 30 d Rb1 intervention. Results reveal that the systemic exposure and metabolic clearance rate of Rb1 and Rd were substantially affected after orally supplementing Rb1 (60 mg/kg) to rats. Significant increase in the relative abundance of Bacteroides cellulosilyticus in gut microbiota and specific glycoside hydrolase (GH) families, such as GH2, GH92, and GH20 were observed based on microbiome and metagenomic analysis. Moreover, a robust association was identified between the pharmacokinetic parameters of Rb1 and the relative abundance of specific Bacteroides species, and glycoside hydrolase families. Our study demonstrates that Rb1 administration significantly affects the gut microbiome, revealing a complex relationship between B. cellulosilyticus, key GH families, and Rb1 pharmacokinetics.

The dry matter content in buffalo milk is relatively high, and its comprehensive nutritional value, which is higher than that of ordinary milk, is considered a good source of various bioactive components. Therefore, buffalo milk and its related products are receiving increasing attention from consumers. In this paper, the contents of protein, fat, carbohydrate and other nutrients in buffalo milk and their physical and chemical properties are introduced according to the cutting-edge research results on buffalo milk nutrients and their products. Meanwhile, the preparation and related research of buffalo milk dairy products, such as cheese, cream, yogurt and ice cream are summarized. Finally, this paper provides some insights on the possibility of developing functional food based on bioactive substances in buffalo milk and reference for enterprises to develop buffalo-milk-related products.

Yeast has been an indispensable host for synthesizing complex plant-derived natural compounds, yet the yields remained largely constrained. This limitation mainly arises from overlooking the importance of cell and pathway suitability during the optimization of enzymes and pathways. Herein, beyond conventional enzyme engineering, we dissected metabolic suitability with a framework for simultaneously augmenting cofactors and carbon flux to enhance the biosynthesis of heterogenous triterpenoids. We further developed phospholipid microenvironment engineering strategies, dramatically improving yeast's suitability for the high performance of endoplasmic reticulum (ER)-localized, rate-limiting plant P450s. Combining metabolic and microenvironment suitability by manipulating only three genes, NHMGR (NADH-dependent HMG-CoA reductase), SIP4 (a DNA-binding transcription factor)and GPP1 (Glycerol-1-phosphate phosphohydrolase 1), we enabled the high-level production of 4.92 g/L rare licorice triterpenoids derived from consecutive oxidation of β-amyrin by two P450 enzymes after fermentation optimization. This production holds substantial commercial value, highlighting the critical role of establishing cell suitability in enhancing triterpenoid biosynthesis and offering a versatile framework applicable to various plant natural product biosynthetic pathways.

ABSTRACT: Objectives: The emergence of carbapenem-resistant Klebsiella pneumoniae presents significant health challenges. Here, we present the structural genome sequence of an NDM-5–producing K. pneumoniae (HZKP2) in China. Methods: Antimicrobial susceptibility tests were conducted via broth microdilution. Whole-genome sequencing was performed for genomic analysis. Wzi and capsular polysaccharide (KL) were analysed using Kaptive. Resistance genes, virulence factors, and comparative genomics analyses were also conducted. Multilocus sequence typing (MLST), replicons type, and core genome MLST analysis were further conducted using BacWGSTdb server. Results: HZKP2 was resistant to cefepime, ceftazidime, ciprofloxacin, ciprofloxacin, meropenem, and ertapenem. It harboured fosA, blaSHV-187, oqxA, oqxB, sul1, dfrA1, tet(A), floR, aph(6)-Id, aph(3′')-Ib, sul2, blaCTX-M-55, and blaNDM-5. Based on the RAST results, 5563 genes that belonged to 398 subsystems were annotated. The complete genome sequence of HZKP2 was characterized as ST1, wzi 19, and KL19, 5 five contigs totalling 5 654 446 bp, including one chromosome and four plasmids. Further analysis found that blaNDM-5 was located in a 46 161 bp IncX3 plasmid (pHZKP2-3). The genetic structure of blaNDM-5 gene was ISKox3-IS26-bleMBL-blaNDM-5-IS5-ISAb125-IS3000. Further analysis revealed that insertion sequences mediated the dissemination of blaNDM-5 from other species of Enterobacterales. Phylogenetic analysis showed that the closest relative was from a human stool specimen in China, which differed by 53 core genome MLST alleles. Conclusions: Our study provides the first structural perspective of the ST1 K. pneumoniae isolate producing NDM-5 in China. These results could provide valuable insights into the genetic characteristics, antimicrobial resistance mechanisms, and transmission dynamics of carbapenem-resistant K. pneumoniae in clinical settings.

For marine soft soil under the periodic wave loading, the pore water content in soil suffering dry-wet cycle for a long time, which affects its microstructure and macroscopic mechanical strength, resulting in insufficient bearing capacity and excessive deformation of soft soil. To reveal the microstructural characteristics and strength attenuation law of marine soft soil under dry-wet cycle condition, electron microscopy scanning and direct shear tests under different times of dry-wet cycles were carried out, and the mathematical equations of pore structure and strength parameters were established based on fractal theory. The research results showed that: (1) The pore structure changed considerably after the first dry-wet cycle, and then changed gently with the increase of dry-wet cycle times, which was reflected by the fractal dimension D value decreases to a constant value gradually. (2) The shear strength of the soil diminishes with an increase in the number of dry-wet cycle times, and the maximum attenuation occurs after the first dry-wet cycle. (3) The relationship between cohesion (c), internal friction angle (φ), and fractal dimension (D) is exponential, with the curve shapes being concave and convex, respectively.

Vascular calcification and vascular ageing are “silent” diseases but are highly prevalent in patients with end stage renal failure and type 2 diabetes, as well as in the ageing population. Melatonin (MT) has been shown to induce cardiovascular protection effects. However, the role of MT on vascular calcification and ageing has not been well-identified. In this study, the aortic transcriptional landscape revealed clues for MT related cell-to-cell communication between endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) in vascular calcification and vascular ageing. Furthermore, we elucidated that it was exosomes that participate in the information transportation from ECs to VSMCs. The exosomes secreted from melatonin-treated ECs (MT-ECs-Exos) inhibited calcification and senescence of VSMCs. Mechanistically, miR-302d-5p was highly enriched in MT-ECs-Exos, while depletion of miR-302d-5p blocked the ability of MT-ECs-Exos to suppress VSMC calcification and senescence. Notably, Wnt3 was a bona fide target of miR-302d-5p and modulated VSMC calcification and senescence. Furthermore, we found that maturation of endothelial derived exosomal miR-302d-5p was promoted by WTAP in an N6-methyladenosine (m6A)-dependent manner. Interestingly, MT alleviated vascular calcification and ageing in 5/6-nephrectomy (5/6 NTP) mice, a chronic kidney disease (CKD) induced vascular calcification and vascular ageing mouse model. MT-ECs-Exos was absorbed by VSMCs in vivo and effectively prevented vascular calcification and ageing in 5/6 NTP mice. ECs-derived miR-302d-5p mediated MT induced anti-calcification and anti-ageing effects in 5/6 NTP mice. Our study suggests that MT-ECs-Exos alleviate vascular calcification and ageing through the miR-302d-5p/Wnt3 signaling pathway, dependent on m6A methylation.

ABSTRACTBackground Traditional vaccine development, often a lengthy and costly process of three separated phases. However, the swift development of COVID-19 vaccines highlighted the critical importance of accelerating the approval of vaccines. This article showcases a seamless phase 2/3 trial design to expedite the development process, particularly for multi-valent vaccines.Research Design and Methods This study utilizes simulation to compare the performance of seamless phase 2/3 design with that of conventional trial design, specifically by re-envisioning a 9-valent HPV vaccine trial. Across three cases, several key performance metrics are evaluated: overall power, type I error rate, average sample size, trial duration, the percentage of early stop, and the accuracy of dose selection.Results On average, when the experimental vaccine was assumed to be effective, the seamless design that performed interim analyses based solely on efficacy saved 555.73 subjects, shortened trials by 10.29 months, and increased power by 3.70%. When the experimental vaccine was less effective than control, it saved an average of 887.73 subjects while maintaining the type I error rate below 0.025.Conclusion The seamless design proves to be a compelling strategy for vaccine development, given its versatility in early stopping, re-estimating sample sizes, and shortening trial durations.

Abstract Background UV-B, an important environmental factor, has been shown to affect the yield and quality of rice (Oryza sativa) worldwide. However, the molecular mechanisms underlying the response to UV-B stress remain elusive in rice. Results We perform comprehensive metabolic profiling of leaves from 160 diverse rice accessions under UV-B and normal light conditions using a widely targeted metabolomics approach. Our results reveal substantial differences in metabolite accumulation between the two major rice subspecies indica and japonica, especially after UV-B treatment, implying the possible role and mechanism of metabolome changes in subspecies differentiation and the stress response. We next conduct a transcriptome analysis from four representative rice varieties under UV-B stress, revealing genes from amino acid and flavonoid pathways involved in the UV-B response. We further perform a metabolite-based genome-wide association study (mGWAS), which reveals 3307 distinct loci under UV-B stress. Identification and functional validation of candidate genes show that OsMYB44 regulates tryptamine accumulation to mediate UV-B tolerance, while OsUVR8 interacts with OsMYB110 to promote flavonoid accumulation and UV-B tolerance in a coordinated manner. Additionally, haplotype analysis suggests that natural variation of OsUVR8 groupA contributes to UV-B resistance in rice. Conclusions Our study reveals the complex biochemical and genetic foundations that govern the metabolite dynamics underlying the response, tolerance, and adaptive strategies of rice to UV-B stress. These findings provide new insights into the biochemical and genetic basis of the metabolome underlying the crop response, tolerance, and adaptation to UV-B stress.

Abstract Background The relationship between human gut microbiota and high-altitude hypoxia acclimatization remains highly controversial. This stems primarily from uncertainties regarding both the potential temporal changes in the microbiota under such conditions and the existence of any dominant or core bacteria that may assist in host acclimatization. Results To address these issues, and to control for variables commonly present in previous studies which significantly impact the results obtained, namely genetic background, ethnicity, lifestyle, and diet, we conducted a 108-day longitudinal study on the same cohort comprising 45 healthy Han adults who traveled from lowland Chongqing, 243 masl, to high-altitude plateau Lhasa, Xizang, 3658 masl, and back. Using shotgun metagenomic profiling, we study temporal changes in gut microbiota composition at different timepoints. The results show a significant reduction in the species and functional diversity of the gut microbiota, along with a marked increase in functional redundancy. These changes are primarily driven by the overgrowth of Blautia A, a genus that is also abundant in six independent Han cohorts with long-term duration in lower hypoxia environment in Shigatse, Xizang, at 4700 masl. Further animal experiments indicate that Blautia A-fed mice exhibit enhanced intestinal health and a better acclimatization phenotype to sustained hypoxic stress. Conclusions Our study underscores the importance of Blautia A species in the gut microbiota’s rapid response to high-altitude hypoxia and its potential role in maintaining intestinal health and aiding host adaptation to extreme environments, likely via anti-inflammation and intestinal barrier protection.

Abstract DNA polymerase ζ (Pol ζ) plays an essential role in replicating damaged DNA templates but contributes to mutagenesis due to its low fidelity. Therefore, ensuring tight control of Pol ζ’s activity is critical for continuous and accurate DNA replication, yet the specific mechanisms remain unclear. This study reveals a regulation mechanism of Pol ζ activity in human cells. Under normal conditions, an autoinhibition mechanism keeps the catalytic subunit, REV3L, inactive. Upon encountering replication stress, however, ATR-mediated phosphorylation of REV3L’s S279 cluster activates REV3L and triggers its degradation via a caspase-mediated pathway. This regulation confines the activity of Pol ζ, balancing its essential role against its mutations causing potential during replication stress. Overall, our findings elucidate a control scheme that fine tunes the low-fidelity polymerase activity of Pol ζ under challenging replication scenarios.

Abstract Rationale Warthin tumor (WT) is the second most common benign tumor in salivary gland. It has a slow growth rate and most frequently occurs in the parotid gland. Most patients present with an incidental finding of a painless mass inferior/anterior to the ear. Besides the epithelial component of the tumor, WT is characteristically associated with lymphoid stroma that is considered benign. While there have been a few reports of malignant transformation of the lymphoid components in WT, cases of WT concomitant with mantle cell lymphoma (MCL) are extremely rare. To the best of our knowledge, two cases have been described in the English literature. Herein, we report a case of WT concomitant with MCL in a 70-year-old female patient, and emphasize the importance of careful examination of lymphoid stroma in WT so that concurrent lymphoma is not missed. Patient concerns A 70-year-old Chinese woman with a 40-year history of cigarette smoking presented with a one year history of a right submaxillary mass with recent enlargement. Diagnosis Cervical ultrasound (US) and computed tomography (CT) scans of the neck revealed a well-circumscribed mass in the right parotid with a maximum diameter of 3.1 cm. Surgical resection of the mass was performed. Histopathological examination revealed a characteristic double-layer of neoplastic epithelium with prominent lymphoid stroma, suggesting WT. In addition, morphology and immunohistochemistry studies confirmed the coexistence of MCL. Thereafter, the final diagnosis of this case was WT concomitant with MCL. Interventions The patient was staged as stage I after clinical assessment. Due to the slow growth of parotid lesions, close observation was decided with periodic clinical and radiological monitoring. Outcomes Currently, the patient demonstrates a stable disease by clinical evaluation. Lessons To the best of our knowledge, reported cases of WT concomitant with MCL are very rare. This case highlights the importance of a comprehensive assessment of the lymphoid stroma of WT to avoid missed diagnosis of a lymphoma component in a collision tumor.

Abstract Background The prognostic value of the pretreatment prognostic nutritional index (PNI) for gynaecological malignancies remain unclear. This meta-analysis aimed to explore the predictive significance of the PNI for gynaecological tumours. Methods The PubMed, Embase, Web of Science, and Cochrane Library databases were searched up to January 30, 2024, to identify relevant studies. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to assess the associations of the PNI with overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) in patients with gynaecological tumours. We examined the correlation of the PNI with clinicopathological parameters of patients with gynaecological carcinoma by utilizing pooled odds ratios (ORs) and 95% CIs. Results A total of 28 articles involving 9,428 patients were included in the meta-analysis. The results revealed that a low PNI significantly predicted worse OS (HR = 1.60, 95% CI: 1.39–1.84, P

Abstract Purpose Our study aimed to develop and validate a homologous recombination deficiency (HRD) scoring algorithm in the Chinese breast cancer population. Methods and materials Ninety-six in-house breast cancer (BC) samples and 6 HRD-positive standard cells were analyzed by whole-genome sequencing (WGS). Besides, 122 BCs from the TCGA database were down-sampled to ~ 1X WGS. We constructed an algorithm named AcornHRD for HRD score calculated based on WGS at low coverage as input data to estimate large-scale copy number alteration (LCNA) events on the genome. A clinical cohort of 50 BCs (15 cases carrying BRCA mutation) was used to assess the association between HRD status and anthracyclines-based neoadjuvant treatment outcomes. Results A 100-kb window was defined as the optimal size using 41 in-house cases and the TCGA dataset. HRD score high threshold was determined as HRD score ≥ 10 using 55 in-house BCs with BRCA mutation to achieve a 95% BRCA-positive agreement rate. Furthermore, the HRD status agreement rate of AcornHRD is 100%, while the ShallowHRD is 60% in standard cells. BRCA mutation was significantly associated with a high HRD score evaluated by AcornHRD and ShallowHRD (p = 0.008 and p = 0.003, respectively) in the TCGA dataset. However, AcornHRD showed a higher positive agreement rate than did the ShallowHRD algorithm (70% vs 60%). In addition, the BRCA-positive agreement rate of AcornHRD was superior to that of ShallowHRD (87% vs 13%) in the clinical cohort. Importantly, the high HRD score assessed by AcornHRD was significantly correlated with a residual cancer burden score of 0 or 1 (RCB0/1). Besides, the HRD-positive group was more likely to respond to anthracycline-based chemotherapy than the HRD-negative group (pCR [OR = 9.5, 95% CI 1.11–81.5, p = 0.040] and RCB0/1 [OR = 10.29, 95% CI 2.02–52.36, p = 0.005]). Conclusion Using the AcornHRD algorithm evaluation, our analysis demonstrated the high performance of the LCNA genomic signature for HRD detection in breast cancers.

Abstract Stretchable electronics commonly assemble multiple material modules with varied bulk moduli and surface chemistry on one packaging substrate. Preventing the strain-induced delamination between the module and the substrate has been a critical challenge. Here we develop a packaging substrate that delivers mechanically stable module/substrate interfaces for a broad range of stiff and stretchable modules with varied surface chemistries. The key design of the substrate was to introduce module-specific stretchability and universal adhesiveness by regionally tuning the bulk molecular mobility and surface molecular polarity of a near-hermetic elastic polymer matrix. The packaging substrate can customize the deformation of different modules while avoiding delamination upon stretching up to 600%. Based on this substrate, we fabricated a fully stretchable bioelectronic device that can serve as a respiration sensor or an electric generator with an in vivo lifetime of 10 weeks. This substrate could be a versatile platform for device assembly.

Abstract Background Extracellular matrix (ECM) remodeling in skeletal muscle is a significant factor in the development of sarcopenia. This study aims to evaluate changes in ECM remodeling in the lumbar paravertebral muscles of sarcopenic rats using diffusion-tensor magnetic resonance imaging (DT-MRI) and compare them with histology. Methods Twenty 6-month-old female Sprague Dawley rats were randomly divided into the dexamethasone (DEX) group and the control (CON) group. Both groups underwent 3.0T MRI scanning, including Mensa, T2WI, and DT-MRI sequences. The changes in muscle fibers and extracellular matrix (ECM) of the erector spinal muscle were observed using hematoxylineosin and sirius red staining. The expressions of collagen I, III, and fibronectin in the erector spinae were detected by western blot. Pearson correlation analysis was employed to assess the correlation between MRI quantitative parameters and corresponding histopathology markers. Results The cross-sectional area and fractional anisotropy values of the erector spinae in the DEX group rats were significantly lower than those in the CON group (p

Abstract Spinal cord injury (SCI) is a complex tissue injury that results in a wide range of physical deficits, including permanent or progressive disabilities of sensory, motor and autonomic functions. To date, limitations in current clinical treatment options can leave SCI patients with lifelong disabilities. There is an urgent need to develop new therapies for reconstructing the damaged spinal cord neuron-glia network and restoring connectivity with the supraspinal pathways. Neural stem cells (NSCs) possess the ability to self-renew and differentiate into neurons and neuroglia, including oligodendrocytes, which are cells responsible for the formation and maintenance of the myelin sheath and the regeneration of demyelinated axons. For these properties, NSCs are considered to be a promising cell source for rebuilding damaged neural circuits and promoting myelin regeneration. Over the past decade, transplantation of NSCs has been extensively tested in a variety of preclinical models of SCI. This review aims to highlight the pathophysiology of SCI and promote the understanding of the role of NSCs in SCI repair therapy and the current advances in pathological mechanism, pre-clinical studies, as well as clinical trials of SCI via NSC transplantation therapeutic strategy. Understanding and mastering these frontier updates will pave the way for establishing novel therapeutic strategies to improve the quality of recovery from SCI.

Abstract In the geothermal development of hot dry rock (HDR), both the drilling of the wellbore and the heat exchange of the heat reservoir involve the effects of different cold and hot conditions on the high-temperature rock mass. The testing machine for rock mechanics was used to conduct a uniaxial compression test and carry out micro testing on the treated samples; furthermore, with the help of scanning electron microscopy the fracture mechanism of granite subjected to different temperatures and cooling methods was studied. The results show: (1) With the gradual increase in temperature, the compressive strength of granite under the two cooling methods gradually decreases. (2) The failure modes of the samples under the two cooling methods are mainly shear failure of the "Y" type. The degree of damage of the sample under water cooling is significantly greater than that under natural cooling. Electron micrographs could confirm these results. (3) It can be obtained by testing the mineral composition and element changes of granite at different temperatures. When the temperature reaches 600℃, its change is more pronounced. The results of this study can provide a theoretical reference for the failure of the wellbore and the degree of fracture of the thermal reservoir rock mass during geothermal development.

The genus Lucasioides Kwon, 1993 (Isopoda: Oniscidea: Agnaridae) occurs in Asia, but confined only to China, Japan, Korea, and Russian Siberia. The ambiguously morphological differences among some members of the genus make a dilemma: the species recognition, whether morphologically similar or different, is uncertain. In this paper, we present first morphometric and molecular data for the genus from a broad sample. DNA sequences (mitochondrial COI, nuclear 18S rRNA, 28S rRNA, and NaK) were generated and integrated with morphological evidence to reveal the cryptic species and delimit the new species within the genus. Seven species are described as new to science: Lucasioides digitatus sp. nov., L. dissectus sp. nov., L. dianensis sp. nov., L. formosus sp. nov., L. gracilentus sp. nov., L. schmidti sp. nov. and L. subcurvatus sp. nov. To date, Lucasioides species from China are 44.4% as many as all the known congeners worldwide, showing the exceptional species diversity of Lucasioides species from China. The results demonstrate that the integrative taxonomy is especially important to reveal the cryptic species among the high morphological similarity of taxa, as well as providing an effective way for species identification to accelerate the exploration of woodlice biodiversity.

Objective As a charismatic species, cashmere goats have rich genetic resources. In the Inner Mongolia Autonomous Region, there are three cashmere goat varieties named and approved by the state. These goats are renowned for their high cashmere production and superior cashmere quality. Therefore, it is vitally important to protect their genetic resources as they will serve as breeding material for developing new varieties in the future. Methods Three breeds including Inner Mongolia cashmere goats (IMCG), Hanshan White cashmere goats (HS), and Ujimqin white cashmere goats (WZMQ) were studied. IMCG were of three types: Aerbas (AEBS), Erlangshan (ELS), and Alashan (ALS). Nine DNA samples were collected for each population, and they were genomically re-sequenced to obtain high-depth data. The genetic diversity parameters of each population were estimated to determine selection intensity. Principal component analysis, phylogenetic tree construction and genetic differentiation parameter estimation were performed to determine genetic relationships among populations. Results Samples from the 45 individuals from the five goat populations were sequenced, and 30,601,671 raw single nucleotide polymorphisms (SNPs) obtained. Then, variant calling was conducted using the reference genome, and 17,214,526 SNPs were retained after quality control. Individual sequencing depth of individuals ranged from 21.13× to 46.18×, with an average of 28.5×. In the AEBS, locus polymorphism (79.28) and expected heterozygosity (0.2554) proportions were the lowest, and the homologous consistency ratio (0.1021) and average inbreeding coefficient (0.1348) were the highest, indicating that this population had strong selection intensity. Conversely, ALS and WZMQ selection intensity was relatively low. Genetic distance between HS and the other four populations was relatively high, and genetic exchange existed among the other four populations. Conclusion The Inner Mongolia cashmere goat (AEBS type) population has a relatively high selection intensity and a low genetic diversity. The IMCG (ALS type) and WZMQ populations had relatively low selection intensity and high genetic diversity. The genetic distance between HS and the other four populations was relatively high, with a moderate degree of differentiation. Overall, these genetic variations provide a solid foundation for resource identification of Inner Mongolia Autonomous Region cashmere goats in the future.

Ultraviolet (UV) radiation causes skin damage including oxidative stress, inflammation, and photoaging. Extremophile fermentation products have been found to effectively protect the skin from UV-induced damage. This study aimed to investigate the impact of acid-induced stress on the content of bioactive compounds, as well as the anti-inflammatory and anti-photoaging properties of sorghum fermentation by the extremophilic Monascus pilosus. The study compared acid-stress fermentation (ASF) of sorghum with conventional fermentation (CF) and examined differences in total phenolic content, antioxidant activity, and short-chain fatty acid levels. Using gas chromatography–mass spectrometry assay, the ASF sample had lower total phenolic content compared to CF, but significantly higher levels of short-chain fatty acids. Butyric acid was the predominant metabolite in the ASF sample, followed by propionic acid. The ASF sample exhibited superior protection for UV-irradiated human keratinocytes by inhibiting apoptosis, reducing ROS, and downregulating inflammatory mediators. It also decreased metalloproteinases expression levels, increased collagen and elastin production, and mitigated UV-induced photoaging. The effects of ASF samples were evaluated in volunteers, and the results confirmed the ASF sample's effectiveness in ameliorating UV-induced skin symptoms, including pigmentation, redness, and wrinkles. These findings conclude that acid-stress enhances the anti-inflammatory and anti-photoaging capabilities of Monascus pilosus fermented sorghum.

Abstract Urban greening is becoming an important strategy in improving urban ecosystem services and sustainability. Identifying the response of vegetation to urbanization and urban landscape patterns can help in planning for urban greening. Urbanization may lead to both direct and indirect effects on vegetation, and the indirect effects of urbanization on vegetation growth (UIE-VG) have been paid much attention recently in large scale. In this study, we investigated the spatiotemporal evolution of UIE-VG and the effects of landscape patterns on UIE-VG using the boosted regression tree model and remotely sensed data. An increase in average UIE-VG from 4 to 56% was found during urbanization of Kunming, the case study area in southwest China. However, UIE-VG exhibited high variations due to landscape pattern changes at the local scale. Overall, area-related and aggregation-related landscape metrics had greater effects on UIE-VG than the other metrics. The increase and aggregation of built-up land enhanced UIE-VG by 3.1–81.3% while the increase and aggregation of unused land and waterbodies reduced UIE-VG by 0.7–20.6%. Moreover, we found that the large and aggregated vegetation areas may mitigate the negative UIE-VG in low urbanization areas. Our findings have important implications for integrating urban landscape planning into sustainable urban greening strategies.

Abstract AI Generated Content Law was extensively promoted in 2023; hence, it is crucial to uncover factors influencing people’s behavioral intentions to comply with the AI Generated Content Law. This study extends the theory of planned behavior to explore the factors influencing people to follow AI Generated Content Law in China. In addition to the factors in TPB model, such as one’s attitudinal factors, normative factors, and perceived behavioral control, we add another factor-moral obligation to extend the theory of planned behavior model. We used convenient sampling and there were 712 effective samples. Using the statistical software Amos17.0, the result shows that attitude, subjective norms, perceived behavioral control and moral obligation all have positive effects on intentions to follow AI Generated Content Law.

The Gaoligong Mountains are characterized by large variations in elevation and topography, which support high levels of biodiversity and endemism that remain largely understudied. Herein, based on the integration of morphological comparisons and phylogenetic reconstruction, we describe a new species of Rhacophorus from the northern Gaoligong Mountains, Yunnan Province, China. The new species, Rhacophorus dulongensis sp. nov., is morphologically distinguishable from its congeners based on the differences in body size, head length, tibia length, snout and tongue shape, toe webbing formula and coloration, ventral skin texture and coloration, dorsal pattern and coloration, body macroglands, iris coloration, and pattern of markings on flanks. Phylogenetically, it differs from its congeners by uncorrected p-distances of >4.8% for the 16S rRNA gene fragment. Rhacophorus dulongensis sp. nov. is likely to be found in Myanmar, considering its type locality lies close to the China-Myanmar border. The phylogenetic analysis revealed that the “widespread” species, R. rhodopus, is a species complex and a composite of five distinct lineages. The results revealed that R. napoensis is also found in Vietnam, making it a new country record for Vietnam. Interestingly, R. dulongensis sp. nov. likely breeds in bamboo, a hidden behavioral characteristic that makes them easy to overlook. Given the ongoing habitat loss and degradation in the region, further biological exploration is urgently needed in the Gaoligong Mountains as a biodiversity reservoir.

Abstract Objective Currently, there are still some shortcomings in EBM education in China.The study aimed to investigate the effectiveness of the novel evidence-based medicine (EBM) learning model of “autonomy-collaboration.” Methods A total of 91 undergraduate students majoring in clinical medicine at Zhongshan Clinical College of Dalian University from the 2019 batch were selected as the participants in this study. They were instructed to follow the EBM learning model of “autonomy-collaboration.” Upon completion of the course, questionnaires, records of participants’ sentiments and insights, and evidence-based clinical practice reports were used as indicators to evaluate the effectiveness of the training. Results This learning modality effectively enhanced independent learning ability of the students, stimulated their interest in learning, and strengthened the communication between students and teachers, thereby improving the quality of teaching. Conclusion The novel EBM learning model of “autonomy-collaboration,” exhibited robust effectiveness in instruction and facilitated the seamless integration of theoretical knowledge with clinical practice. Consequently, its widespread adoption is strongly recommended.

Abstract Two-dimensional topological insulators hosting the quantum spin Hall effect have application potential in dissipationless electronics. To observe the quantum spin Hall effect at elevated temperatures, a wide band gap is indispensable to efficiently suppress bulk conduction. Yet, most candidate materials exhibit narrow or even negative band gaps. Here, via elegant control of van der Waals epitaxy, we have successfully grown monolayer ZrTe5 on a bilayer graphene/SiC substrate. The epitaxial ZrTe5 monolayer crystalizes in two allotrope isomers with different intralayer alignments of ZrTe3 prisms. Our scanning tunneling microscopy/spectroscopy characterization unveils an intrinsic full band gap as large as 254 meV and one-dimensional edge states localized along the periphery of the ZrTe5 monolayer. First-principles calculations further confirm that the large band gap originates from strong spin−orbit coupling, and the edge states are topologically nontrivial. These findings thus provide a highly desirable material platform for the exploration of the high-temperature quantum spin Hall effect.