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Objective: We analyze the characteristics and related factors of human chorionic gonadotropin (hCG) of pituitary origin to establish the reference interval to resolve clinical confusion and avoid harmful therapy to Chinese postmenopausal women with “positive” hCG. Materials and methods: This retrospective cohort study identified individuals who underwent hCG measurements at an academic hospital. Three gonadotropins (hCG, follicle stimulating hormone (FSH), and luteinizing hormone (LH)) was drawn from medical records. The age-stratified analyses were performed first. Then the correlations of hCG and FSH, LH as well as age were analysed. Finally, characteristics and associations of hCG, LH, and FSH were evaluated to identify pituitary hCG in postmenopausal women in clinical settings. Results: In total, 9796 cases from 11172 records met inclusion criteria and contributed 9796 hCG, 7541 FSH, and 7536 LH values. The upper reference interval for our cohorts was 5.3 IU/L. HCG, FSH, and LH concentration had no significant correlations with age. HCG moderately correlated with FSH (r = 0.47) and LH level (r = 0.53). However, it was FSH but not LH that manifested good clinical applicability. Conclusion: The prevalence of hCG≥5.0 IU/L and 5.3 IU/L in women ≥55 years is 2.8% and 2.3% in the study population from China. The level of hCG 5.3 IU/L was suggested to be the positive threshold for postmenopausal women. FSH≥40IU/L helps to distinguish the pituitary source of hCG in postmenopausal women whose serum hCG concentrations were between 5.3 and 16 IU/L.

Dysregulated inflammation after trauma or infection could result in the further disease and delayed tissue reconstruction. The conventional anti-inflammatory drug treatment suffers to the poor bioavailability and side effects. Herein, we developed an amphiphilic multifunctional poly (citrate-polyglycol-curcumin) (PCGC) nano oligomer with the robust anti-inflammatory activity for treating acute lung injury (ALI) and Methicillin-resistant staphylococcus aureus (MRSA) infected wound. PCGC demonstrated the sustained curcumin release, inherent photoluminescence, good cellular compatibility, hemocompatibility, robust antioxidant activity and enhanced cellular uptake. PCGC could efficiently scavenge nitrogen-based free radicals, oxygen-based free radicals, and intracellular oxygen species, enhance the endothelial cell migration and reduce the expression of pro-inflammatory factors through the NF-κB signal pathway. Combined the anti-inflammation and antioxidant properties, PCGC can shortened the inflammatory process. In animal model of ALI, PCGC was able to reduce the pulmonary edema, bronchial cell infiltration, and lung inflammation, while exhibiting rapid metabolic behavior in vivo. The MRSA-infection wound model showed that PCGC significantly reduced the expression of pro-inflammatory factors, promoted the angiogenesis and accelerated the wound healing. The transcriptome sequencing and molecular mechanism studies further demonstrated that PCGC could inhibit multiple inflammatory related pathways including TNFAIP3, IL-15RA, NF-κB. This work demonstrates that PCGC is efficient in resolving inflammation and promotes the prospect of application in inflammatory diseases as the drug-loaded therapeutic system.

Abstract Background The role of histone methyltransferase SETDB1 in renal ischemia–reperfusion (I/R) injury has not been explored yet. This study aims to investigate the potential mechanism of SETDB1 in regulating renal I/R injury and its impact on mitochondrial damage and oxidative stress. Methods The in vivo model of renal I/R in mice and the in vitro model of hypoxia/reoxygenation (H/R) in human renal tubular epithelial cells (HK-2) were constructed to detect the expression of SETDB1. Next, the specific inhibitor (R,R)-59 and knockdown viruses were used to inhibit SETDB1 and verify its effects on mitochondrial damage and oxidative stress. Chromatin immunoprecipitation (ChIP) and coimmunoprecipitation (CoIP) were implemented to explore the in-depth mechanism of SETDB1 regulating renal I/R injury. Results The study found that SETDB1 had a regulatory role in mitochondrial damage and oxidative stress during renal I/R injury. Notably, SESN2 was identified as a target of SETDB1, and its expression was under the influence of SETDB1. Besides, SESN2 mediated the regulation of SETDB1 on renal I/R injury. Through deeper mechanistic studies, we uncovered that SETDB1 collaborates with heterochromatin HP1β, facilitating the labeling of H3K9me3 on the SESN2 promoter and impeding SESN2 expression. Conclusions The SETDB1/HP1β-SESN2 axis emerges as a potential therapeutic strategy for mitigating renal I/R injury.

Abstract Wheat is a crucial crop worldwide, and accurate detection and counting of wheat spikes are vital for yield estimation and breeding. However, these tasks are daunting in complex field environments. To tackle this, we introduce RIA-SpikeNet, a model designed to detect and count wheat spikes in such conditions. First, we introduce an Implicit Decoupling Detection Head to incorporate more implicit knowledge, enabling the model to better distinguish visually similar wheat spikes. Second, Asymmetric Loss is employed as the confidence loss function, enhancing the learning weights of positive and hard samples, thus improving performance in complex scenes. Lastly, the backbone network is modified through reparameterization and the use of larger convolutional kernels, expanding the effective receptive field and improving shape information extraction. These enhancements significantly improve the model’s ability to detect and count wheat spikes accurately. RIA-SpikeNet outperforms the state-of-the-art YOLOv8 detection model, achieving a competitive 81.54% mAP and 90.29% R2. The model demonstrates superior performance in challenging scenarios, providing an effective tool for wheat spike yield estimation in field environments and valuable support for wheat production and breeding efforts.

Abstract Background Interlaminar endoscopic lumbar discectomy (IELD) is a prevalent method for managing lumbar disc herniation. Local anesthesia (LA) is frequently employed during IELD, albeit with its merits and drawbacks. The spinal anesthesia (SA) represents a feasible anesthetic strategy for IELD; however, the availability of clinical research data is currently limited. Methods The propensity score matching was conducted to ensure the comparability of the SA and LA groups. The outcome measures were operation time, intraoperative visual analogue scale (VAS) for pain, need for adjuvant analgesia, intraoperative vital signs, blood loss, adverse surgical events, anesthesia-related complications, postoperative bed rest duration, VAS for pain at 2 h postoperatively, Oswestry Disability Index score (ODI), satisfaction with surgical efficacy, and willingness to undergo reoperation at 6 months postoperatively. Results Fifty-six patients were assigned to each group. Significant differences were found between the groups regarding intraoperative VAS for pain, use of adjuvant analgesics, willingness to undergo reoperation, maximum intraoperative systolic blood pressure, and variability (P 0.05). Conclusion SA as an alternative anesthesia for IELD surgery holds great promise, exhibiting superior efficacy compared to LA. However, it is crucial to meticulously evaluate the indications due to potential risks associated with this form of anesthesia.

Abstract Background Endonucleases play a crucial role in plant growth and stress response by breaking down nuclear DNA. However, the specific members and biological functions of the endonuclease encoding genes in wheat remain to be determined. Results In this study, we identified a total of 26 TaENDO family genes at the wheat genome-wide level. These genes were located on chromosomes 2 A, 2B, 2D, 3 A, 3B, and 3D and classified into four groups, each sharing similar gene structures and conserved motifs. Furthermore, we identified diverse stress-response and growth-related cis-elements in the promoter of TaENDO genes, which were broadly expressed in different organs, and several TaENDO genes were significantly induced under drought and salt stresses. We further examined the biological function of TaENDO23 gene since it was rapidly induced under drought stress and exhibited high expression in spikes and grains. Subcellular localization analysis revealed that TaENDO23 was localized in the cytoplasm of wheat protoplasts. qRT-PCR results indicated that the expression of TaENDO23 increased under PEG6000 and abscisic acid treatments, but decreased under NaCl treatment. TaENDO23 mainly expressed in leaves and spikes. A kompetitive allele-specific PCR (KASP) marker was developed to identify single nucleotide polymorphisms in TaENDO23 gene in 256 wheat accessions. The alleles with TaENDO23-HapI haplotypes had higher grain weight and size compared to TaENDO23-HapII. The geographical and annual frequency distributions of the two TaENDO23 haplotypes revealed that the elite haplotype TaENDO23-HapI was positively selected in the wheat breeding process. Conclusion We systematically analyzed the evolutionary relationships, gene structure characteristics, and expression patterns of TaENDO genes in wheat. The expression of TaENDO23, in particular, was induced under drought stress, mainly expressed in the leaves and grains. The KASP marker of TaENDO23 gene successfully distinguished between the wheat accessions, revealing TaENDO23-HapI as the elite haplotype associated with improved grain weight and size. These findings provide insights into the evolution and characteristics of TaENDO genes at the genome-wide level in wheat, laying the foundation for further biological analysis of TaENDO23 gene, especially in response to drought stress and grain development.

Abstract Herpes simplex virus (HSV), an epidemic human pathogen threatening global public health, gains notoriety for its complex pathogenesis that encompasses lytic infection of mucosal cells, latent infection within neurons, and periodic reactivation. This intricate interplay, coupled with HSV's sophisticated immune evasion strategies, gives rise to various diseases, including genital lesions, neonatal encephalitis, and cancer. Despite more than 70 years of relentless research, an effective preventive or therapeutic vaccine against HSV has yet to emerge, primarily due to the limited understanding of virus-host interactions, which in turn impedes the identification of effective vaccine targets. However, HSV's unique pathological features, including its substantial genetic load capacity, high replicability, transmissibility, and neurotropism, render it a promising candidate for various applications, spanning oncolytic virotherapy, gene and immune therapies, and even as an imaging tracer in neuroscience. In this review, we comprehensively update recent breakthroughs in HSV pathogenesis and immune evasion, critically summarize the progress made in vaccine candidate development, and discuss the multifaceted applications of HSV as a biological tool. Importantly, we highlight both success and challenges, emphasizing the critical need for intensified research into HSV, with the aim of providing deeper insights that can not only advance HSV treatment strategies but also broaden its application horizons.

Abstract The giant river prawn (Macrobrachium rosenbergii) is one of the most widely cultured crustacean species. In recent years, its aquaculture has faced challenges, including the degradation of germplasm resources and the emergence of viral diseases. Genomic information can be a valuable resource for developing molecular breeding programs for this important aquaculture species. Here we constructed a high-quality reference genome for M. rosenbergii by integrating Nanopore, Illumina, and high-throughput chromosome conformation capture (Hi-C) technologies. The final genome assembly is 3.18 Gb in size, with scaffold N50 and contig N50 of 62.73 Mb and 8.92 Mb, respectively. Approximately 98.6% of the assembled sequences were anchored into 59 pseudo-chromosomes. Benchmarking Universal Single-Copy Orthologs (BUSCO) benchmark of the genome assembly reached 94.5%. Repetitive sequences comprise 43.77% of the assembled genome, and 17,436 protein-coding genes were annotated. The high-quality genome of M. rosenbergii will empower molecular breeding efforts and provide invaluable resources for comparative genomic analysis of decapod species.

Abstract Background The Hippo pathway is a conserved tumour suppressor signalling pathway, and its dysregulation is often associated with abnormal cell growth and tumorigenesis. We previously revealed that the transcriptional coactivator Yes-associated protein (YAP), the key effector of the Hippo pathway, is a molecular target for glioblastoma (GBM), the most common malignant brain tumour. Inhibiting YAP with small interfering RNA (siYAP) or the specific inhibitor verteporfin (VP) can diminish GBM growth to a certain degree. Results In this study, to enhance the anti-GBM effect of siYAP and VP, we designed stepwise-targeting and hypoxia-responsive liposomes (AMVY@NPs), which encapsulate hypoxia-responsive polymetronidazole-coated VP and DOTAP adsorbed siYAP, with angiopep-2 (A2) modification on the surface. AMVY@NPs exhibited excellent blood‒brain barrier crossing, GBM targeting, and hypoxia-responsive and efficient siYAP and VP release properties. By inhibiting the expression and function of YAP, AMVY@NPs synergistically inhibited both the growth and stemness of GBM in vitro. Moreover, AMVY@NPs strongly inhibited the growth of orthotopic U87 xenografts and improved the survival of tumour-bearing mice without adverse effects. Conclusion Specific targeting of YAP with stepwise-targeting and hypoxia-responsive liposome AMVY@NPs carrying siYAP and VP efficiently inhibited GBM progression. This study provides a valuable drug delivery platform and creative insights for molecular targeted treatment of GBM in the future.

Abstract Background Accurate prediction of postoperative vault in implantable collamer lens (ICL) implantation is crucial; however, current formulas often fail to account for individual anatomical variations, leading to suboptimal visual outcomes and necessitating improved predictive models. We aimed to verify the prediction accuracy of our new predictive model for vaulting based on anterior and posterior chamber structural parameters. Methods This retrospective observational study included 137 patients (240 eyes) who previously underwent ICL surgery. Patients were randomly divided into the model establishment (192 eyes) or validation (48 eyes) groups. Preoperative measurements of the anterior and posterior chamber structures were obtained using Pentacam, CASIA2 anterior segment optical coherence tomography (AS-OCT), ultrasound biomicroscopy, and other devices. Stepwise multiple linear regression analysis was used to evaluate the relationship between the vault and each variable (WL formula). The Friedman test was performed for the vaulting prediction results of the WL, NK (Ver. 3), and KS formulas (Ver. 4) in CASIA2 AS-OCT, as well as the Zhu formula and vault measurements. The proportions of prediction error within ± 250 μm per formula were compared. Results The predicted vault values of the WL, NK, KS, and Zhu formulas and vault measurements were 668.74 ± 162.12, 650.85 ± 248.47, 546.56 ± 128.99, 486.56 ± 210.76, and 716.06 ± 233.84 μm, respectively, with a significant difference (χ2 = 69.883, P = 0.000). Significant differences were also found between the measured vault value and Zhu formula, measured vault value and KS formula, WL formula and Zhu formula, WL formula and KS formula, NK formula and KS formula, and NK formula and Zhu formula (P NK formula (70.8%) > KS formula (66.7%) > Zhu formula (54.2%). Conclusions The WL formula, which considers the complexity of the anterior and posterior chamber structures, demonstrates greater calculation accuracy, compared with the KS (Ver. 4) and Zhu formulas. The proportion of absolute prediction error ≤ 250 μm is higher with the WL formula than with the NK formula (ver. 3). This enhanced predictive capability can improve ICL sizing decisions, thereby increasing the safety and efficacy of ICL implantation surgeries.

Abstract Electrochemical reactions via carbocation intermediates remain fundamental transformations that build up molecular functionality and complexity in a sustainable manner. Enantioselective control of such processes is a great challenge in a highly ionic electrolyte solution. Here, we report an anodic generation of chiral α-imino carbocation intermediates by enamine catalysis. The chiral carbocation intermediates can be intercepted by a variety of nucleophiles such as alcohols, water and thiols with high stereoselectivity. The key SN1 step proceeds via a tertiary amine-mediated proton shuttle that facilitates facial selection in reacting with carbocation.

Abstract A macroscopic perspective is indispensable for understanding the intricate relationship between deubiquitinases and tumorigenesis. Proteomics has been proposed as a viable approach for elucidating the complex role of deubiquitylation in cellular progression. Instead of studying the function of a single ubiquitinase, research on a deubiquitinase family with similar catalytic core(s) may provide a new perspective for the pathological understanding of cancer. The Ubiquitin C-terminal hydrolase L (UCHL) family consists of four members: UCHL1, UCHL3, UCHL5, and BRAC1 associated protein-1 (BAP1), and they have been implicated in tumorigenesis and metastasis. Some members are considered hallmarks of intracranial lesions, colon cancer, chromatin remodeling, and histone stability. The present study uncovered an unknown correlation between the UCHL family and renal cancer. We discovered that UCHLs exhibit diverse regulatory effects in renal cancer, establishing connections between the renal cancer and truncated gene mutations, mitochondrial energetic metastasis, immune cell infiltration, and chromosomal stability of UCHLs family. Notably, we found that the increase of UCHL5 expression in renal cancer cells decreases the antigen processing and presentation of RCC tumor-infiltrating B cells. Further research identified that the expression of UCHL5 in RCC tumors is correlated with transport proteins, which led us to find that the abundance of UCHL5 in the blood of late-stage renal cell cancer patients is upregulated from 18 ng/L to 500 ng/L. Therefore, we propose that the abundance of UCHL5 in patients' blood can be a possible indicator of poor prognosis for renal cell cancer.

Abstract Background Atherogenic index of plasma (AIP) has been reported as a critical predictor on the risks and clinical outcomes of cardiovascular diseases (CVDs), and we aimed to explore the potential predictive value of cumulative AIP on major adverse cardiac events (MACE), stroke, myocardial infarction (MI) and cardiovascular mortality. Methods A large-scale community-based prospective cohort was established from December 2011 to April 2012 and followed up in May to July 2014. The endpoint outcomes were obtained before December 31, 2021. AIP was calculated as the logarithmically transformed ratio of triglyceride (TG) to high-density lipoprotein cholesterol (HDL-c) and cumulative AIP was the average value of AIP in 2012 and 2014. Results An overall of 3820 participants (36.1% male) with mean (SD) age of 59.1 (8.7) years, were enrolled. Within a median follow-up of 7.5 years, a total of 371 (9.7%) participants were documented with MACE, 293 (7.7%) participants developed stroke, 68 (1.8%) suffered from MI and 65 (1.7%) experienced cardiovascular mortality. Multivariable Cox regression analysis revealed significant associations between cumulative AIP and the risk of MACE, stroke and MI. Regarding MACE, individuals with one higher unit of cumulative AIP were associated with 75% increment on the incidence of going through MACE in fully adjusted model, while categorizing participants into four groups, individuals in the highest cumulative AIP quartile were significantly associated with increased incidence of MACE (HR = 1.76, 95%CI: 1.27–2.44, p

The increasing utilization of transparent ceramics in laser systems, particularly the magnesium aluminate spinel (MgAl2O4) transparent ceramic, has positioned it as the primary candidate for high energy laser system exit windows. Nevertheless, the increased energy and power of laser output necessitate higher standards for the laser-induced damage threshold in transparent ceramics. Residual micropores within transparent ceramics pose a potential source of damage. In this study, we employed the post-annealing process to effectively modulate the density and size of micropores. We first established the relationship between the density and size of micropores and laser damage threshold, which described the damage morphology of transparent ceramic in detail. Subsequently, we developed a multi-physical field coupled kinetic model of laser damage in micropores, providing a quantitative analysis of how factors such as micropore size and density influence the damage morphology of transparent ceramic surfaces when subjected to laser irradiation. Using time-resolved pumping and probing technology, we conducted in situ detection of laser damage caused by micropores, enabling detailed examination of damage kinetic behavior. Ultimately, this study elucidated the physical mechanism behind micropore-induced transparent ceramic damage. This has significant implications for enhancing the anti-laser damage performance of transparent ceramics in high-intensity laser systems.

In this study, the effect of heat treatment on the microstructure and mechanical properties of 2209 duplex stainless steel fabricated by wire arc additive was analyzed. It was found that solution treatment at 1100°C for 2 hours and tempering at 300°C for 2 hours can effectively improve the grain inhomogeneity of 2209 duplex stainless steel, eliminate γ2 and harmful brittle phases, and take into account the mechanical properties and corrosion resistance. Compared with the original deposition state, the hardness and yield strength increased by 10% and 31.8% to 245.6 HV and 499.7 MPa, which meet the requirements of engineering propellers. Electron back-scattered diffraction studies showed that the grains became refined and austenite maintained //Z orientation after solution heat treatment. Many small-angle grain boundaries were present in both the original sample and the solid solution, but further tempering transformed the small-angle grain boundaries into large-angle grain boundaries.

Abstract Latent bioreactive unnatural amino acids (Uaas) have been widely used in the development of covalent drugs and identification of protein interactors, such as proteins, DNA, RNA and carbohydrates. However, it is challenging to perform high-throughput identification of Uaa cross-linking products due to the complexities of protein samples and the data analysis processes. Enrichable Uaas can effectively reduce the complexities of protein samples and simplify data analysis, but few cross-linked peptides were identified from mammalian cell samples with these Uaas. Here we develop an enrichable and multiple amino acids reactive Uaa, eFSY, and demonstrate that eFSY is MS cleavable when eFSY-Lys and eFSY-His are the cross-linking products. An identification software, AixUaa is developed to decipher eFSY mass cleavable data. We systematically identify direct interactomes of Thioredoxin 1 (Trx1) and Selenoprotein M (SELM) with eFSY and AixUaa.

Chlorine-rich Li-argyrodite sulfide solid electrolytes Li5.5PS4.5Cl1.5 are applied in all-solid-state batteries (ASSBs) due to the promising ionic transport and structural stability. However, the poor air/moisture stability and incompatibility to Li metal impede their practical applications. Herein, we synthesized a Li5.5PS4.5Cl1.5-based argyrodite exhibiting improved moisture stability and electrochemical performance to metallic Li, as well as high-voltage cathodes through O doping. The prepared oxygen-doped Li5.5PS4.5Cl1.5 samples (Li5.5PS4.425O0.075Cl1.5) possess significantly enhanced air stability and lower migration barrier in comparison with pristine Li5.5PS4.5Cl1.5. Moreover, Li5.5PS4.425O0.075Cl1.5 exhibits lower polarization voltage and better compatibility with lithium metal in the constant current charge-discharge tests of Li-Li symmetrical cell. This is attributed to the Cl-O coexistence coating interface that observed in the interface of Li/Li5.5PS4.425O0.075Cl1.5. To fully leverage the ultrafast ionic conductivity of Li5.5PS4.5Cl1.5, we construct ASSBs using optimized Li5.5PS4.425O0.075Cl1.5 as buffer layer between pristine LiNi0.6Mn0.2Co0.2O2 cathode materials and Li5.5PS4.5Cl1.5, leading to higher discharge capacities and elevated capacity retention. Based on above results, we further introduce LiNbO3-coated LiCoO2 as cathode, combined with Li5.5PS4.425O0.075Cl1.5 as an isolating layer between Li anode and Li5.5PS4.5Cl1.5 to suppress the growth of Li dendrite and achieve superior cyclability at wide voltage windows. Consequently, the all-solid-state lithium batteries exhibit promising application in a wide temperature range. This work provides a compelling strategy for achieving improved Chlorine-rich Li-argyrodite solid electrolytes with excellent air stability, high ionic conductivity and Li dendrite suppression capability, hence enabling all-solid-state batteries with high energy density and superior cyclability.

Abstract Seven in absentia proteins, which contain a conserved SINA domain, are involved in regulating various aspects of wheat (Triticum aestivum L.) growth and development, especially in response to environmental stresses. However, it is unclear whether TaSINA family members are involved in regulating grain development until now. In this study, the expression pattern, genomic polymorphism, and relationship with grain‐related traits were analyzed for all TaSINA members. Most of the TaSINA genes identified showed higher expression levels in young wheat spikes or grains than other organs. The genomic polymorphism analysis revealed that at least 62 TaSINA genes had different haplotypes, where the haplotypes of five genes were significantly correlated with grain‐related traits. Kompetitive allele‐specific PCR markers were developed to confirm the single nucleotide polymorphisms in TaSINA101 and TaSINA109 among the five selected genes in a set of 292 wheat accessions. The TaSINA101‐Hap II and TaSINA109‐Hap II haplotypes had higher grain weight and width compared to TaSINA101‐Hap I and TaSINA109‐Hap I in at least three environments, respectively. The qRT‐PCR assays revealed that TaSINA101 was highly expressed in the palea shell, seed coat, and embryo in young wheat grains. The TaSINA101 protein was unevenly distributed in the nucleus when transiently expressed in the protoplast of wheat. Three homozygous TaSINA101 transgenic lines in rice (Oryza sativa L.) showed higher grain weight and size compared to the wild type. These findings provide valuable insight into the biological function and elite haplotype of TaSINA family genes in wheat grain development at a genomic‐wide level.

Shunt capacitor banks are essential for reactive power compensation, ensuring voltage stability, and reducing system losses. These banks consist of multiple units with components in series and parallel. A few component failures do not immediately affect the safe operation of the capacitor bank, but component breakdown can lead to voltage redistribution. Under combined factors such as system overvoltage and equipment aging, and others can trigger an avalanche effect causing capacitor breakdown, resulting in significant safety accident risks. Practical operation experience shows that partial component breakdown generates many transient disturbance signals. Quantitative analysis of these signals can detect capacitor bank anomalies early. This paper proposes the quantitative extraction of transient disturbance characteristics using the Prony algorithm and estimates the phase and number of capacitors that break down to judge capacitor anomalies. The simulation part verifies the theoretical analysis and detection algorithm’s correctness through numerical simulations and PSCAD (Power Systems Computer Aided Design) electromagnetic transient simulations. The numerical simulations consider different signal lengths, noise levels, attenuation coefficients, and oscillation frequencies. In the PSCAD simulation environment, verification models are built under varying sampling frequencies, numbers of breakdown components, signal lengths, and signal-to-noise ratios. These simulation results verify the accuracy of the detection algorithm under different conditions.

Summary: LC is one of the most common malignant tumours that often presents with no distinct symptoms in the early stages, leading to late diagnoses when patients are at an advanced stage and no longer suitable for surgical treatment. Although adjuvant treatments are available, patients frequently develop tolerance to these treatments over time, resulting in poor prognoses for patients with advanced LC. Recently, circular RNAs (circRNAs), a type of non-coding RNA, have gained significant attention in LC research. Owing to their unique circular structure, circRNAs are highly stable within cells. This review systematically summarises the expression, characteristics, biological functions, and molecular regulatory mechanisms of circRNAs involved in therapy resistance as well as the potential applications in early diagnosis and gene targeting therapy in LC.

In order to find new potential fungicides and anticancer agents, a series of new coumarin amide derivatives bearing fluorine were synthesized and characterized spectroscopically. Compounds A6, B11, C2 and C7 were confirmed by X-ray diffraction further. The antifungal bioassays against five typical pathogenic fungi showed that compound C5 exhibited more remarkable fungicidal activities against Alternaria alternata (EC50 = 11.5 μg/mL), Colletotrichum gloeosporioides (EC50 = 18.0 μg/mL), Pyricularia grisea (EC50 = 33.8 μg/mL), surpassing kresoxim-methyl. Molecular docking result indicated that C5 displayed high binding affinity to chitinase, which plays crucial role in degradation and remodeling of fungal cell walls. In addition, the anticancer bioassays against three cancer cells demonstrated that compound A4 displayed excellent growth inhibitory effect against Hela cells with IC50 value of 8.13 μM, and low cytotoxicity against human normal cells BEAS-2B. Flow cytometric analysis further demonstrated that A4 significantly arrested cell cycle at the S phase and trigger apoptosis. With the above interesting biological profile, these coumarin derivatives could be used as anfungicides and anticancer candidates.

Andrographolide is the main active ingredient of Andrographis paniculata, which has the functions of clearing heat and detoxifying, antibacterial and anti-inflammatory, protecting liver and improving gallbladder. It is clinically used to treat pneumonia in children and upper respiratory tract infection. In recent years, because of the influence of environmental factors for a long time, not high purity and good varieties of selective breeding work lag and so on reasons, greatly restricted the quality improvement of andrographolide. In the quality evaluation of A. paniculata, the content of andrographolide is a very important index. Analyzing the molecular mechanism and accumulation rule of andrographolide biosynthesis is helpful to improve the quality of A. paniculata. In this review, the biosynthetic pathways and regulatory molecular mechanisms of andrographolide are comprehensively discussed. The biosynthesis of andrographolide is mainly divided into two stages, including the synthesis stage of andrographolide precursor and the modification stage of andrographolide synthesis. The synthesis of precursor has been relatively clear, but the mining of the pathways and key enzymes in the modification stage of andrographolide synthesis is still at a blank, and further research is needed. Through the excavation of the key factors affecting the synthesis and accumulation of andrographolide from the two levels of environmental factors and cropping systems, it is conducive to the establishment of a perfect and high-quality A. paniculata cultivation system. In addition, the research progress on the regulation of andrographolide biosynthesis was summarized and prospected, in order to provide research reference for the improvement of A. paniculata quality.

Locusts and other migratory grasshoppers are transboundary pests. Monitoring and control, therefore, involve a complex system made up of social, ecological, and technological factors. Researchers and those involved in active management are calling for more integration between these siloed but often interrelated sectors. In this paper, we bring together 38 coauthors from six continents and 34 unique organizations, representing much of the social-ecological-technological system (SETS) related to grasshopper and locust management and research around the globe, to introduce current topics of interest and review recent advancements. Together, the paper explores the relationships, strengths, and weaknesses of the organizations responsible for the management of major locust-affected regions. The authors cover topics spanning humanities, social science, and the history of locust biological research and offer insights and approaches for the future of collaborative sustainable locust management. These perspectives will help support sustainable locust management, which still faces immense challenges such as fluctuations in funding, focus, isolated agendas, trust, communication, transparency, pesticide use, and environmental and human health standards. Arizona State University launched the Global Locust Initiative (GLI) in 2018 as a response to some of these challenges. The GLI welcomes individuals with interests in locusts and grasshoppers, transboundary pests, integrated pest management, landscape-level processes, food security, and/or cross-sectoral initiatives.

Abstract The direct alkenylation with simple alkenes stands out as the most ideal yet challenging strategy for obtaining high-valued desaturated alkanes. Here we present a direct asymmetric dehydrogenative α-C(sp3)-H alkenylation of carbonyls based on synergistic photoredox-cobalt-chiral primary amine catalysis under visible light. The ternary catalytic system enables the direct coupling of β-keto-carbonyls and alkenes through a cooperative radical addition-dehydrogenation process involving a chiral α-imino radical and Co(II)-metalloradical intermediate. A catalytic H-transfer process involving nitrobenzene is engaged to quench in situ generated cobalt hydride species, ensuring a chemoselective alkenylation in good yields and high enantioselectivities.

Triosephosphate isomerase (TPI) is an enzyme that functions in plant energy production, accumulation, and conversion. To understand its function in maize, we characterized a maize TPI mutant, zmtpi4. In comparison to the wild type, zmtpi4 mutants showed altered ear development, reduced kernel weight and starch content, modified starch granule morphology, and altered amylose and amylopectin content. Protein, ATP, and pyruvate contents were reduced, indicating ZmTPI4 was involved in glycolysis. Although subcellular localization confirmed ZmTPI4 as a cytosolic rather than a plastid isoform of TPI, the zmtpi4 mutant showed reduced leaf size and chlorophyll content. Overexpression of ZmTPI4 in Arabidopsis led to enlarged leaves and increased seed weight, suggesting a positive regulatory role of ZmTPI4 in kernel weight and starch content. We conclude that ZmTPI4 functions in maize kernel development, starch synthesis, glycolysis, and photosynthesis.

Abstract Micro RNAs (miRs) have been implicated in various tumorigenic processes. Osteosarcoma (OS) is a primary bone malignancy seen in adolescents. However, the mechanism of miRs in OS has not been fully demonstrated yet. Here, miR-134-5p was found to inhibit OS progression and was also expressed at significantly lower levels in OS tissues and cells relative to normal controls. miR-134-5p was found to reduce vasculogenic mimicry, proliferation, invasion, and migration of OS cells, with miR-134-5p knockdown having the opposite effects. Mechanistically, miR-134-5p inhibited expression of the ITGB1/MMP2/PI3K/Akt axis, thus reducing the malignant features of OS cells. In summary, miR-134-5p reduced OS tumorigenesis by modulation of the ITGB1/MMP2/PI3K/Akt axis, suggesting the potential for using miR-134-5p as a target for treating OS.

Abstract Background Ubiquitination is an important regulatory step of selective protein degradation in the plant UPS (ubiquitin–proteasome system), which is involved in various biological processes in eukaryotes. Ubiquitin-conjugating enzymes play an intermediate role in the process of protein ubiquitination reactions and thus play an essential role in regulating plant growth and response to adverse environmental conditions. However, a genome-wide analysis of the UBC gene family in wheat (Triticum aestivum L.) has not yet been performed. Results In this study, the number, physiochemical properties, gene structure, collinearity, and phylogenetic relationships of TaUBC family members in wheat were analyzed using bioinformatics methods. The expression pattern of TaUBC genes in different tissues/organs and developmental periods, as well as the transcript levels under abiotic stress treatment, were analyzed using RNA-Seq data and qRT-PCR. Meanwhile, favorable haplotypes of TaUBC25 were investigated based on wheat resequencing data of 681 wheat cultivars from the Wheat Union Database. The analyses identified a total of 93 TaUBC family members containing a UBC domain in wheat genome. These genes were unevenly distributed across 21 chromosomes, and numerous duplication events were observed between gene members. Based on phylogenetic analysis, the TaUBC family was divided into 13 E2 groups and a separate UEV group. We investigated the expression of TaUBC family genes under different tissue/organ and stress conditions by quantitative real-time PCR (qRT-PCR) analysis. The results showed that some TaUBC genes were specifically expressed in certain tissues/organs and that most TaUBC genes responded to NaCl, PEG6000, and ABA treatment with different levels of expression. In addition, we performed association analysis for the two haplotypes based on key agronomic traits such as thousand-kernel weight (TKW), kernel length (KL), kernel weight (KW), and kernel thickness (KT), examining 122 wheat accessions at three environmental sites. The results showed that TaUBC25-Hap II had significantly higher TKW, KL, KW, and KT than TaUBC25-Hap I. The distribution analysis of haplotypes showed that TaUBC25-Hap II was preferred in the natural population of wheat. Conclusion Our results identified 93 members of the TaUBC family in wheat, and several genes involved in grain development and abiotic stress response. Based on the SNPs detected in the TaUBC sequence, two haplotypes, TaUBC25-Hap I and TaUBC25-Hap II, were identified among wheat cultivars, and their potential value for wheat breeding was validated by association analysis. The above results provide a theoretical basis for elucidating the evolutionary relationships of the TaUBC gene family and lay the foundation for studying the functions of family members in the future.

Abstract Background Larval settlement and metamorphosis represent critical events in the life history of marine benthic animals. Myoinhibitory peptide (MIP) plays a pivotal role in larval settlement of marine invertebrates. However, the molecular mechanisms of MIP involved in this process are not well understood. Results In this study, we evaluated the effects of thirteen MIP mature peptides on triggering the larval settlement of Urechis unicinctus (Xenopneusta, Urechidae), and determined that MIP2 was the principal neuropeptide. Transcriptomic analysis was employed to identify differentially expressed genes (DEGs) between the MIP2-treated larvae and normal early-segmentation larvae. Both cAMP and calcium signaling pathways were enriched in the DEGs of the MIP2-treated larvae, and two neuropeptide receptor genes (Spr, Fmrfar) were up-regulated in the MIP2-treated larvae. The activation of the SPR-cAMP pathway by MIP2 was experimentally validated in HEK293T cells. Furthermore, fourteen cilia-related genes, including Tctex1d2, Cfap45, Ift43, Ift74, Ift22, Cav1 and Mns1, etc. exhibited down-regulated expression in the MIP2-treated larvae. Whole-mount in situ hybridization identified two selected ciliary genes, Tctex1d2 and Cfap45, were specially expressed in circumoral ciliary cells of the early-segmentation larvae. Knocking down Tctex1d2 mRNA levels by in vivo RNA interference significantly increased the larval settlement rate. Conclusion Our findings suggest that MIP2 inhibits the function of the cilia-related genes, such as Tctex1d2, through the SPR-cAMP-PKA pathway, thereby inducing larval settlement in U. unicinctus. The study contributes important data to the understanding of neuropeptide regulation in larval settlement.

Abstract Insufficient attention has been given to the recycling of excess urea despite its potential detrimental effects on soil nutrient equilibrium, geological structure, and crop health. In this study, corncob-derived porous biochar (CPB), which is rich in surface functional groups, was prepared from biomass corncob in two steps as an adsorbent to remove urea from wastewater. Compared with the typical carbonization and activation processes, this process resulted in a higher yield of CPB and an ultrahigh adsorption capacity for urea. Response surface analysis was utilized to determine the optimal carbonization conditions, which were found to be 500 °C for 6 h with a heating rate of 15 °C/min. The exceptional adsorption capability of CPB can be ascribed to its porous structure and significant presence of oxygen-containing functional groups, which facilitate a synergistic interaction of physisorption and chemisorption. This adsorption phenomenon aligns with the Harkins–Jura isotherm model and adheres to pseudo-second order kinetics. CPB demonstrates potential as an adsorbent for the elimination of urea from wastewater in an economical and effective fashion.

Abstract Background Lung adenocarcinoma (LUAD) is the predominant histological subtype of lung cancer and the leading cause of cancer-related mortality. Identifying effective drug targets is crucial for advancing LUAD treatment strategies. Methods This study employed proteome-wide Mendelian randomization (MR) and colocalization analyses. We collected data on 1394 plasma proteins from a protein quantitative trait loci (pQTL) study involving 4907 individuals. Genetic associations with LUAD were derived from the Transdisciplinary Research in Cancer of the Lung (TRICL) study, including 11,245 cases and 54,619 controls. We integrated pQTL and LUAD genome-wide association studies (GWASs) data to identify candidate proteins. MR utilizes single nucleotide polymorphisms (SNPs) as genetic instruments to estimate the causal effect of exposure on outcome, while Bayesian colocalization analysis determines the probability of shared causal genetic variants between traits. Our study applied these methods to assess causality between plasma proteins and LUAD. Furthermore, we employed a two-step MR to quantify the proportion of risk factors mediated by proteins on LUAD. Finally, protein–protein interaction (PPI) analysis elucidated potential links between proteins and current LUAD medications. Results We identified nine plasma proteins significantly associated with LUAD. Increased levels of ALAD, FLT1, ICAM5, and VWC2 exhibited protective effects, with odds ratios of 0.79 (95% CI 0.72–0.87), 0.39 (95% CI 0.28–0.55), 0.91 (95% CI 0.72–0.87), and 0.85 (95% CI 0.79–0.92), respectively. Conversely, MDGA2 (OR, 1.13; 95% CI 1.08–1.19), NTM (OR, 1.12; 95% CI 1.09–1.16), PMM2 (OR, 1.35; 95% CI 1.18–1.53), RNASET2 (OR, 1.15; 95% CI 1.08–1.21), and TFPI (OR, 4.58; 95% CI 3.02–6.94) increased LUAD risk. Notably, none of the nine proteins showed evidence of reverse causality. Bayesian colocalization indicated that RNASET2, TFPI, and VWC2 shared the same variant with LUAD. Furthermore, NTM and FLT1 demonstrated interactions with targets of current LUAD medications. Additionally, FLT1 and TFPI are currently under evaluation as therapeutic targets, while NTM, RNASET2, and VWC2 are potentially druggable. These findings shed light on LUAD pathogenesis, highlighting the tumor-promoting effects of RNASET2, TFPI, and NTM, along with the protective effects of VWC2 and FLT1, providing a significant biological foundation for future LUAD therapeutic targets. Conclusions Our proteome-wide MR analysis highlighted RNASET2, TFPI, VWC2, NTM, and FLT1 as potential drug targets for further clinical investigation in LUAD. However, the specific mechanisms by which these proteins influence LUAD remain elusive. Targeting these proteins in drug development holds the potential for successful clinical trials, providing a pathway to prioritize and reduce costs in LUAD therapeutics.

Background: Recently, the osteogenic potential of Adiponectin-labeled adipogenic lineage progenitors (Adipoq-lineage progenitors) in bone marrow has been observed to support bone maintenance and repair. However, little is known about the function of Schnurri-3 (SHN3, also known as HIVEP3) in other mesenchymal lineage cells, apart from its negative regulation of bone formation on osteoblasts. Method: In this study, we used single-cell RNA sequencing (scRNA-seq) profiling to demonstrate that Adipoq-lineage progenitors express higher levels of Shn3 compared to other mesenchymal cell populations in mice and humans. To investigate the role of SHN3 in Adipoq-lineage progenitors, we generated a murine model specifically harboring a Shn3-deficient allele in Adipoq-expressing cells. Information of mice body weight was collected weekly to generate body weight curve. Bone phenotype was analyzed using micro-CT and histomorphometric studies. To eliminate the role of peripheral adipose tissue on bone, we collected adipose wet weight, performed intraperitoneal glucose tolerance tests and intraperitoneal insulin tolerance tests, and conducted a fat-transplantation study. Osteoblast and osteoclast functions were assessed through toluidine blue staining and TRAP staining, respectively. We further investigated the effect of Shn3 depletion on the differentiation of Adipoq-lineage progenitors through immunostaining and in vitro differentiation assays. Finally, we evaluated whether Shn3 deficiency in Adipoq-lineage progenitors affects the fracture healing process by generating bi-cortical femoral fracture models. Results: Depletion of Shn3 in Adipoq-lineage progenitors resulted in a significant increase in trabecular bone mass and bone formation in vivo, without disrupting whole-body energy metabolism and skeletal development. Consistent with these findings, both cell-lineage tracing and functional assays revealed that Shn3 ablation effectively shifted the cell fate of Adipoq-lineage progenitors towards an osteogenic phenotype in the bone marrow. Furthermore, in vivo studies demonstrated that the lack of Shn3 in Adipoq-lineage progenitors also enhanced bone fracture healing under pathological conditions. Conclusion: Overall, our findings provide a novel strategy for targeting the osteoanabolic potential of bone marrow Adipoq-lineage progenitors as a potential treatment for bone loss-related disorders. Translational potential of this article: We have identified a novel gene target that directs the cell fate of a previously identified non-osteogenic cell population under physiological conditions. This study not only expands the therapeutic value of Shn3 ablation in treating osteoporotic or traumatic bone diseases but also provides new insights into the contribution of bone marrow Adipoq-lineage progenitors to osteogenesis. Thus, this article further supports Shn3 silencing as a valuable approach to treat osteopenia and accelerate fracture healing (see graphical abstract)

Abstract The occurrence of many autoimmune diseases takes root on the disrupted balance among Treg cells, Teff cells, etc. Low-dose interleukin-2 (IL-2) cytokine demonstrates promising clinical efficacy in the expansion of Treg cells and the treatment of autoimmune diseases. However, its clinical application is hindered by the small therapeutic index and short half-life. Previous studies have shown that non-covalent complex of human IL-2 and anti-IL-2 antibody biases cytokine activity towards Treg cells and extends IL-2’s half-life. The clinical translation of such complex is non-trivial. In this study, we discover an anti-human IL-2 antibody and engineer a covalently-linked single-agent fusion of human IL-2 and its antibody that selectively expands Treg cells and exhibits superior disease control activity in animal models of ulcerative colitis and systemic lupus erythematosus, with proper safety profile and good developability. These studies pave the road for its clinical development in diverse autoimmune diseases.

Objectives Transplant renal artery stenosis (TRAS) is now recognized as a curable disease with a good prognosis if intervention occurs in the early stage. However, the mid-term outcomes of TRAS when treated by percutaneous transluminal angioplasty with stent placement have yet to be fully elucidated. The purpose of this study was to compare mid-term graft and patient survival of TRAS group with a control group.Patients and methods Ninety-two patients were diagnosed of TRAS between January 2016 and January 2022 in our center. Fifty-six pairs of recipients with grafts from the same donor were selected as a study group with TRAS and a control group without TRAS, respectively. All donor kidneys were from deceased organ donation rather than living donors. The primary endpoints were graft and patient survival. The secondary outcomes were changes in renal graft function.Results The mean follow-up time for the TRAS group was 43.6 months, while the mean follow-up time for the control group was 45.3 months. In the TRAS group, the age of patients ranged from 11 to 62 years with 39 males and 17 females. In the control group, the age of patients ranged from 18 to 67 years with 40 males and 16 females. In the TRAS group, there were more patients with diabetic nephropathy as the primary renal disease compared to the control group (5/56 vs 0/56), and the incidence of acute rejection was higher in the TRAS group than in the control group (12/56 vs 3/56). Eight patients in the TRAS group and one patient in the control group experienced graft loss (p = .019). Four patients in the TRAS group and four patients in the control group died with functional renal allograft during the follow-up time (p = .989). The levels of eGFR did not differ significantly between the two groups in the first three years after kidney transplant (p > .05). Patients in the TRAS group had worse graft functionality (eGFR, 44.96 ± 18.9 vs 54.9 ± 19.6 mL/min) in the fourth year when compared with the control group (p = .01).Conclusions The graft function deteriorated faster, and graft survival was lower in the TRAS group treated by stent placement when compared with a control group without TRAS over the mid-term.

Abstract This study aimed to investigate the effects of adding different levels (0, 50, 100, 200 and 300 mg/kg) of dietary β‐carotene on the color and flavor quality of adult female E. sinensis ovaries. Adding moderate amount of β‐carotene to the feed could regulate the distribution of carotenoids, fatty acids, and free amino acids in the ovaries of E. sinensis, as well as increase the content of total carotenoids, total fatty acids, sweet and umami amino acids in the ovaries. The dietary β‐carotene have limited coloring effects and a significant impact on the flavor of the ovaries. During thermal process, the addition of 100 mg/kg β‐carotene could effectively promote formation of aroma precursors and generate more characteristic aroma components (2‐methylbutanal, 3‐methylbutanal, hexanal, benzaldehyde, methylpyrazine). However, excessive β‐carotene supplementation (300 mg/kg) led to adverse effects on physiological metabolism and flavor of E. sinensis ovaries. Considering both feed cost and quality improvement, β‐carotene supplementation at 100 mg/kg can be considered the optimal feed supplementation for adult female E. sinensis within a 70‐day rearing period to improve edible quality of ovaries.

IntroductionPrevious research has established associations between alterations in gut microbiota composition and various gynecologic tumors. However, establishing a causal relationship between gut microbiota and these tumors remains necessary. This study employs a two-sample Mendelian randomization (MR) approach to investigate causality, aiming to identify pathogenic bacterial communities potentially involved in gynecologic tumor development.MethodsData from the MiBioGen consortium’s Genome-Wide Association Study (GWAS) on gut microbiota were used as the exposure variable. Four common gynecologic neoplasms, including uterine fibroids (UF), endometrial cancer (EC), ovarian cancer (OC), and cervical cancer (CC), were selected as outcome variables. Single-nucleotide polymorphisms (SNPs) significantly associated with gut microbiota were chosen as instrumental variables (IVs). The inverse variance-weighted (IVW) method was used as the primary MR analysis to assess the causal relationship. External validation An was conducted using an independent. Sensitivity analyses were performed to ensure robustness. Reverse MR analysis was also conducted to assess potential reverse causation.ResultsCombining discovery and validation cohorts, we found that higher relative abundance of Lachnospiraceae is associated with lower UF risk (OR: 0.882, 95% CI: 0.793-0.982, P = 0.022). Conversely, higher OC incidence is associated with increased relative abundance of Lachnospiraceae (OR: 1.329, 95% CI: 1.019–1.732, P = 0.036). Sensitivity analyses confirmed these findings’ reliability. Reverse MR analysis showed no evidence of reverse causation between UF, OC, and Lachnospiraceae.DiscussionThis study establishes a causal relationship between Lachnospiraceae relative abundance and both UF and OC. These findings provide new insights into the potential role of gut microbiota in mechanisms underlying gynecological tumors development.

Background: Zhiqiao Gancao decoction (ZQGCD) was created by Professor Gong Zhengfeng, a renowned Chinese medicine expert. Clinical studies have shown its efficacy in alleviating pain and enhancing lumbar function in intervertebral disc degeneration (IDD) patients. However, the precise mechanism of ZQGCD in treating IDD remains unclear. Methods: The active components of ZQGCD were identified using Liquid chromatography-tandem mass spectrometry (LC-MS/MS). A rat model of intervertebral disc degeneration was established, and rats in each group received ZQGCD for three weeks. Assessment parameters included hyperalgesia status, observation of intervertebral disc tissue degeneration and macrophage infiltration, and analysis of JAK2/STAT3 pathway protein expression in the intervertebral disc. Primary macrophage M1 polarization was induced using LPS, with cells treated using the JAK2 inhibitor (AZD1480) and ZQGCD to evaluate macrophage polarization, cellular supernatant inflammatory factors, and JAK2/STAT3 pathway expression. Macrophage supernatant served as a conditioned medium to observe its effects on the proliferation of nucleus pulposus cells (NPCs) and the expression of collagen II and MMP3 proteins. Results: A total of 81 active components were identified in ZQGCD. Following ZQGCD treatment, infiltrating macrophages in intervertebral disc tissues of model rats decreased, the content of M1 macrophages decreased, while the content of M2 macrophages increased, the expression of proinflammatory factors and pain-inducing factors in serum decreased, and the expression of substance P in intervertebral disc tissue decreased. Consequently, the intervertebral disc degeneration and hyperalgesia of rats were improved. In vitro studies revealed that LPS induced M1 macrophage polarization. By inhibiting the JAK2/STAT3 pathway, both JAK2 inhibitors and ZQGCD effectively suppressed M1 polarization, resulting in decreased levels of IL-1β, IL-6, TNF-α, and various other inflammatory factors. Consequently, this inhibition led to a delay in the degeneration of NPCs. Conclusion: There is macrophage infiltration in the intervertebral disc tissue of IDD rats, and JAK2/STAT3 pathway is activated, macrophages are polarized to M1 type, resulting in inflammatory microenvironment, leading to intervertebral disc degeneration and hyperalgesia. ZQGCD exhibited a delaying effect on IDD and improved hyperalgesia by inhibiting the JAK2/STAT3/macrophage M1 polarization pathway.

In this paper, the No. 30201 working face of a specific colliery was determined as the study area in the Yushen mining area, China. The objective of this paper is to determine the optimal position for pressure regulation measures during the final mining stage. A mechanical calculation model for stabilized coal pillar was developed. The analytical solution for the front abutment pressure function was obtained. Limit equilibrium theory and beam theory were employed to compute the critical width value of the stabilized coal pillar. The analysis focused on examining the spatiotemporal relationship between the rotational deformation of the main roof and the stability of the retracement channel. The study utilized numerical simulation to investigate the failure characteristics of the surrounding rock and the stress redistribution in the stabilized coal pillar within the working face. Through comprehensive analysis, a reasonable width of 15 m for the stabilized coal pillar was determined and successfully implemented in field practices. A method of using Artificial Neural Network (ANN) to select the stabilized coal pillar width was proposed. The input characteristics of ANN were determined through theoretical analysis. Four models of BP, WOA-BP, PSO-BP, and CPSO-BP were trained. The calculation accuracy of each model is evaluated by three quantitative metrics: MAE, MRE, and RMSE. The MAE value of the CPSO-BP model is 0.9489, showing a reduction of 70.87% compared to the BP model, 55.84% compared to the WOA-BP model, and 51.26% compared to the PSO-BP model. The MRE value is 0.0559, which is 71.51%, 56.29%, and 53.24% lower than the other models, respectively. The RMSE value is 1.0617, which is 68.92%, 56.13%, and 53.03% lower than other models, respectively. The four models were employed to compute the width of the stabilized coal pillar. The values for the BP, WOA-BP, PSO-BP, and CPSO-BP models were 12.7 m, 16.3 m, 14.1 m, and 15.2 m, respectively, indicating that the CPSO-BP model can effectively determine the width of the stabilized coal pillar.

The cure rate for patients with osteosarcoma (OS) has stagnated over the past few decades. Penfluridol, a first-generation antipsychotic, has demonstrated to prevent lung and esophageal malignancies from proliferation and metastasis. However, the effect of penfluridol on OS and its underlying molecular mechanism remains unclear. This study revealed that penfluridol effectively inhibited cell proliferation and migration, and induced G2/M phase arrest in OS cells. In addition, penfluridol treatment was found to increased reactive oxygen species (ROS) levels in OS cells. Combined with the RNA-Seq results, the anti-OS effect of penfluridol was hypothesized to be attributed to the induction of ferroptosis. Western blot results showed that penfluridol promoted intracellular Fe2+ concentration, membrane lipid peroxidation, and decreased intracellular GSH level to induce ferroptosis. Further studies showed that p62/Keap1/Nrf2 signaling pathway was implicated in penfluridol-induced ferroptosis in OS cells. Overexpression of p62 effectively reversed penfluridol-induced ferroptosis. In vivo, penfluridol effectively inhibited proliferation and prolonged survival in xenograft tumor model. Therefore, penfluridol is a promising drug targeting OS in the future.

BackgroundStatins, being the primary pharmacological intervention for hypercholesterolemia, exhibit a notable degree of interpatient variability in their effectiveness, which may be associated with gut microbiota. This study sought to identify the biomarkers for evaluating differences in statin efficacy.MethodsA quasi case-control study was conducted among participants with hypercholesterolemia and coronary heart disease taking rosuvastatin essential. According to the level of low density lipoprotein cholesterol (LDL-C), participants was divided into the “Up to standard” (US) group and the “Below standard” (BS) group. 16S rDNA sequencing and untargeted metabolomics were applied to detected the information of gut microbiota and related metabolites.ResultsA total of 8 US and 8 BS group matched by age and sex were included in the final analysis. 16S rDNA sequencing results indicated that the characteristic strains of the US group were f-Eubacterium_coprostanoligenes and g-Papillibacter, while the characteristic flora of the BS group were o-C0119, g-Pseudolabrys, s-Dyella-Marensis and f-Xanthobacaceae. Metabolomic results suggested that the levels of chenodeoxycholic acid-3-β-D-glucuronide, 1-methylnicotinamide and acetoacetate in stool samples of the US group were significantly higher than those of the BS group. By identifying the differentially abundant bacterial taxa, the gut microbiota could modulate the efficacy of statins through producing enzymes involved in cholesterol metabolism.ConclusionsThe findings suggest that the difference in statin efficacy may be related to gut microbiota strains that can produce short-chain fatty acids and secondary bile acids and affect the efficacy of statins by regulating the activities of cholesterol metabolite-related proteins. Metabolites related to short-chain fatty acids and secondary bile acids in the gut are expected to be biomarkers indicating the efficacy of statins.

The dissimilar metal welding joint is connected by the metallurgical bond of intermetallic compounds at the interface, which easily causes stress concentration at the interface and cracks continuously along the interface, resulting in low reliability in impact environments. A novel multi-layer plug and bolt connection for TC4/7A52 dissimilar metal butt joints is proposed in this manuscript and analyzes the influence mechanism of the structural design on impact toughness. The impact toughness of the Ti/Al composite butt joint is 30.3 J/cm2, which is 2.6 times that of the 7A52 BM. The layered toughening design significantly reduces stress concentrations for the butt joint at impact for the Ti/Al composite butt joint. Upon impact, the Ti/Al composite butt joint does not fracture continuously at the V-notch and exhibits significant macroscopic plastic deformation. For the microstructure of each TC4 and 7A52 layer in the impact fracture, more intragranular slip systems are activated and show a higher dislocation density. Therefore, this structural design can enable dissimilar metals to absorb more impact energy during the impact process.

Coenzyme Q10 (CoQ10) is an essential medicinal ingredient. In this study, we obtained a high-yielding mutant strain of CoQ10, VK-2-3, by subjecting R. sphaeroides V-0 (V-0) to a 12C6+ heavy ion beam and high-voltage prick electric field treatment. To investigate the mutation mechanism, the complete genomes of VK-2-3 and V-0 were sequenced. Collinearity analysis revealed that the nicotinamide adenine dinucleotide-dependent dehydrogenase (NAD) gene underwent rearrangement in the VK-2-3 genome. The NAD gene was overexpressed and silenced in V-0, and this construct was named RS.NAD and RS.ΔNAD. The results showed that the titers of CoQ10 in the RS.NAD and RS.ΔNAD increased and decreased by 16.00 and 33.92%, respectively, compared to those in V-0, and these differences were significant. Our results revealed the mechanism by which the VK-2-3 CoQ10 yield increases through reverse metabolic engineering, providing insights for genetic breeding and mechanistic analysis.

Abstract The rhomboid‐like (RBL) gene encodes serine protease, which plays an important role in the response to cell development and diverse stresses. However, genome‐wide identification, expression profiles, and haplotype analysis of the RBL family genes have not been performed in wheat (Triticum aestivum L.). This study investigated the phylogeny and diversity of the RBL family genes in the wheat genome through various approaches, including gene structure analysis, evolutionary relationship analysis, promoter cis‐acting element analysis, expression pattern analysis, and haplotype analysis. The 41 TaRBL genes were identified and divided into five subfamilies in the wheat genome. RBL family genes were expanded through segmented duplication and purification selection. The cis‐element analysis revealed their involvement in various stress responses and plant development. The results of RNA‐seq and quantitative real‐time‐PCR showed that TaRBL genes displayed higher expression levels in developing spike/grain and were differentially regulated under polyethylene glycol, NaCl, and abscisic acid treatments, indicating their roles in grain development and abiotic stress response. A kompetitive allele‐specific PCR molecular marker was developed to confirm the single nucleotide polymorphism of TaRBL14a gene in 263 wheat accessions. We found that the elite haplotype TaRBL14a‐Hap2 showed a significantly higher 1000‐grain weight than TaRBL14a‐Hap11 in at least three environments, and the TaRBL14a‐Hap2 was positively selected in wheat breeding. The findings will provide a good insight into the evolutionary and functional characteristics of the TaRBL genes family in wheat and lay the foundation for future exploration of the regulatory mechanisms of TaRBL genes in plant growth and development, as well as their response to abiotic stresses.

BackgroundGut microbiome (GM) and type 2 diabetes mellitus (T2DM) have two-way effects. Improving T2DM by modulating GM in various ways, such as diet, exercise, and medication, is gradually becoming popular, and related studies have yielded positive results. However, there is still a lack of high-quality bibliometric analyses of research in this area. This study aims to systematize and comprehensively summarize the knowledge structure, research tropics, and research trends of GM and T2DM through bibliometric analysis.MethodsPublications related to GM and T2DM before January 9, 2024, in the Web of Science Core Collection (WOSCC) were searched in this study. Microsoft Excel 2019 was used to analyze publishing trends and CiteSpace (v.6.1.R6 Advanced) was used to analyze institutions, cited journals, references, and keywords.SCImago Graphica (v.1.0.39) was used to analyze countries/regions, institutions’ collaborations, cited authors, and published journals.ResultsWe finally included 1004 articles published from 2008 to 2023. The number of published articles showed an upward trend and reached its peak in 2022. China is the country with the largest number of articles, Univ Copenhagen is the institution with the largest number of articles, Fukui, Michiaki, Hamaguchi, Masahide are the scholars with the largest number of articles, and Cani and Patrice D. are the scholars with the largest number of citations. NUTRIENTS(Q1/5.9) published the most publications, while Nature (Q1/64.8; Cited 804 times) is the most frequently cited journal. Gut microbiota, Obesity, and insulin resistance are the most frequently used keywords. This study found that current researches focus on the effects of diet, exercise, and pharmacological modification of GM to improve T2DM and explores specific mechanisms. Future researches will focus on three areas: complications of T2DM and specific physiological processes, methods and measures to regulate GM, and new experimental techniques and assays.ConclusionThe current researches confirmed the effects and specific mechanisms of modulating GM to improve T2DM. Further exploration of the effects of modulating GM on T2DM complications and specific physiologic processes is a future trend of research. Exploring specific methods for regulating GM and developing new experimental techniques and assays are important for future research.

ObjectiveInternet addiction and depressive symptoms are common mental health problems in adolescents. Due to the comorbidity of Internet addiction and depressive symptoms, their mutual relationship influences their developmental trajectories over time. Thus, this study aimed to identify the joint trajectories of Internet addiction and depressive symptoms, and examined the individual, family, and school antecedents of these trajectories among Chinese adolescents.MethodsUsing a battery of self-report scales, three waves of data collection were conducted in a Chinese adolescent sample (N = 1,301). The co-developmental trajectories of Internet addiction and depressive symptoms were extracted by adopting parallel-process latent class growth modeling (PPLCGM). Multinomial logistic regression was performed to assess predictive factors.ResultsFour unique joint trajectory classes were detected: the Health Group (n = 912, 70.1%), Comorbidity-Worsening Group (n = 85, 6.5%), Asymptomatic-Comorbid Risk Group (n = 148, 11.4%), and Prominent Depressive Symptoms-Remission Group (n = 156, 12.0%). Individual, family, and school factors (e.g., gender, positive youth development, family function, academic performance) significantly predicted the membership in these distinct co-developmental trajectories.ConclusionOur findings illustrate that the joint development of Internet addiction and depressive symptoms among adolescents presents a heterogeneous distribution, which could better inform prevention and intervention strategies since each co-developmental trajectory may represent unique experience for adolescents who need targeted treatment. Various individual, family, and school factors are important predictors that play different roles in distinguishing the joint trajectories of Internet addiction and depressive symptoms during this critical developmental transition period.