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Abstract Low-grade glioma (LGG) is a primary, slow-growing brain tumor; however, its treatment and prognosis remain challenging. In this study, we analyzed cancer data from the TCGA database, focusing particularly on the expression of the CDKN3 gene in LGG. The results showed that high CDKN3 expression in LGG patients was significantly associated with poor survival outcomes. Further gene expression analysis revealed that 379 genes were significantly upregulated in LGG samples with high CDKN3 expression, and these genes were primarily involved in the mitotic cell cycle and extracellular matrix organization. Additionally, high CDKN3 expression was closely linked to key signaling pathways such as tumor inflammation, hypoxic response, and tumor proliferation. Immune microenvironment analysis showed that high CDKN3 expression significantly increased the expression of CD4 + T cells and specific immune checkpoint genes, suggesting a potentially poor response to immune checkpoint blockade therapy. Through in vitro and in vivo experiments, we confirmed that CDKN3 silencing significantly inhibited the proliferative capacity of LGG cells. Proteomics revealed that CDKN3 can bind ARG1 and inhibite the intracellular arginase activity. These findings not only improve our understanding of LGG biology but also provide scientific evidence for developing potential therapeutic strategies targeting CDKN3.

Abstract Background This study aims to identify a pathogenic SDHD mutation associated with hereditary head and neck paraganglioma (HNPGL) in a Chinese family and to explore its implications for genetic counseling. Methods The study involved a family with 15 members spanning three generations. A 31-year-old patient (II-4) was diagnosed with a left parotid gland tumor and a right carotid body tumor, while both the father and elder sister had right carotid body tumors, and the third sister had bilateral carotid body tumors. Whole exome sequencing and Sanger sequencing were employed to identify candidate pathogenic variants. Genetic counseling was conducted for third-generation descendants to assess the likelihood of carrying the mutation and to guide future diagnosis and treatment. Results A nonsense mutation in the SDHD gene (NM_001276503:exon2:c.C64T: p.R22X) was identified in the patient and three other affected family members. Genetic counseling for the third generation revealed that only one child (III-4) carried the pathogenic mutation inherited from the patient’s third sister. Conclusion We identified a pathogenic mutation in SDHD in a Chinese HNPGL family, which is the second reported case of its kind. Our genetic counseling analysis for the third generation provided important information for the family and guidance for future diagnosis and treatment.

Abstract Bioactive peptides and proteins (BAPPs) are promising therapeutic agents for tissue repair with considerable advantages, including multifunctionality, specificity, biocompatibility, and biodegradability. However, the high complexity of tissue microenvironments and their inherent deficiencies such as short half-live and susceptibility to enzymatic degradation, adversely affect their therapeutic efficacy and clinical applications. Investigating the fundamental mechanisms by which BAPPs modulate the microenvironment and developing rational delivery strategies are essential for optimizing their administration in distinct tissue repairs and facilitating clinical translation. This review initially focuses on the mechanisms through which BAPPs influence the microenvironment for tissue repair via reactive oxygen species, blood and lymphatic vessels, immune cells, and repair cells. Then, a variety of delivery platforms, including scaffolds and hydrogels, electrospun fibers, surface coatings, assisted particles, nanotubes, two-dimensional nanomaterials, and nanoparticles engineered cells, are summarized to incorporate BAPPs for effective tissue repair, modification strategies aimed at enhancing loading efficiencies and release kinetics are also reviewed. Additionally, the delivery of BAPPs can be precisely regulated by endogenous stimuli (glucose, reactive oxygen species, enzymes, pH) or exogenous stimuli (ultrasound, heat, light, magnetic field, and electric field) to achieve on-demand release tailored for specific tissue repair needs. Furthermore, this review focuses on the clinical potential of BAPPs in facilitating tissue repair across various types, including bone, cartilage, intervertebral discs, muscle, tendons, periodontal tissues, skin, myocardium, nervous system (encompassing brain, spinal cord, and peripheral nerve), endometrium, as well as ear and ocular tissue. Finally, current challenges and prospects are discussed.

Abstract Background Patients with light-chain (AL) amyloidosis and concomitant multiple myeloma (MM) are known to have a worse prognosis, while the prognostic implication of cytogenetic abnormalities (CA) and optimal treatment schemes are not well-established. By comparing patients with MM or AL amyloidosis (AL) alone, this study aimed to evaluate the clinical characteristics, CA, and outcomes of patients with AL amyloidosis and concomitant symptomatic MM (MM-AL) and sought to provide evidence for their management. Methods In total, 915 consecutive patients with newly diagnosed AL amyloidosis or MM were retrospectively analyzed. Patients were classified as MM-alone, MM-AL or AL-alone. The presence of symptomatic MM was based on the International Myeloma Working Group criteria, and the diagnosis of AL amyloidosis was confirmed by Congo-red-positive biopsy and immunoelectron microscopy. Results Of 915 patients, 658, 106, and 151 were in the MM-alone group, MM-AL group, and AL-alone group, respectively. The three groups shared a similar incidence rate of CA, while the prevalence of t(11;14) was significantly higher in the AL-alone group than in the MM-AL and MM-alone group (40.7% vs. 25.7% vs. 16.6%, p

Abstract Salix, an economically and ecologically multifunctional tree species widely distributed in China, encompasses five ornamental species sequenced in this study, which are highly beneficial for plant phytoremediation due to their ability to absorb heavy metals. This research utilized high-throughput sequencing to acquire chloroplast genome sequences of Salix, analyzing their gene composition and structural characteristics, identifying potential molecular markers, and laying a foundation for Salix identification and resource classification. Chloroplast DNA was extracted from the leaves of Salix argyracea, Salix dasyclados, Salix eriocephala, Salix integra ‘Hakuro Nishiki’, and Salix suchowensis using an optimized CTAB method. Sequencing was conducted on the Illumina NovaSeq PE150 platform, and bioinformatics tools were employed to compare the structural features and variations within the chloroplast genomes of the Salix. Analysis revealed high similarity among the chloroplast genome sequences of the five Salix species, with a subsequent examination identifying 276, 269, 270, 273, and 273 SSR loci, respectively, along with unique simple repeat sequences in each variety. Comparison of chloroplast genomes across 22 Salix highlighted variations in regions such as matK-trnQ, ndhC-trnV, psbE-petL, rpl36-rps8, and ndhB-rps7, which may serve as valuable molecular markers for willow resource classification studies. In this study, chloroplast genome sequencing and structural analysis of Salix not only enhances the genetic resources of Salix but also forms a critical basis for the development of molecular markers and the exploration of interspecific phylogeny in the genus.

In this study, toroidal soft magnetic composites (SMCs) with the same specifications, positively engraved (FeSiBC–F) and side-engraved (FeSiBC–S) were prepared by pressing FeSiBC amorphous flake powder into a block, and then engraving from the front part and the side part, respectively. In addition, different mass fractions of FeSiBCCr amorphous spherical fine powder were mixed in the FeSiBC flake powder. Therefore, the effects of flake powder orientation and mixed FeSiBCCr fine powder on the magnetic properties of the compound SMCs were investigated deeply. The results show that FeSiBC–F has higher permeability and lower loss than FeSiBC–S as well as FeSiBCCr SMCs. This is because the powder's long axis in FeSiBC–F is parallel to the diameter direction of the SMCs, originating from the demagnetization effect induced by the shape anisotropy of the flake powder. Calculations of the loss separation of the compound SMCs mixed with FeSiBCCr fine powder show that the eddy current energy loss is only 1/120-1/200 of the total energy loss that can be neglected, which is due to the high resistivity and integrity of the insulating layer. While the hysteresis energy loss and excess energy loss are affected by the density of compound SMCs and the volume fraction of non-magnetic pores, which dominate the total energy loss and tend to decrease initially, then increase as the mass fraction of FeSiBCCr amorphous spherical fine powder increases. Compared with pure FeSiBC SMCs, compound SMCs with the optimal microstructure can be obtained by mixing 15 wt% of FeSiBCCr fine powder, resulting in an all-around improvement in comprehensive soft magnetic properties. Its permeability increased from 66.69 to 67.34, and the DC bias performance at 100 Oe improved by 0.77%. The total loss decreased from 165.48 mW/cm³ to 153.39 mW/cm³ at 100 kHz, 500 Gs. It is shown that mixing appropriate amount of amorphous spherical fine powder in FeSiBC amorphous flake powder to fill the non-magnetic pores is an effective way to optimize the microstructure of amorphous SMCs, and to fully utilize the high-frequency soft magnetic properties of amorphous SMCs.

This umbrella review was conducted aiming to assess the association between genetic variations and the development of diabetic retinopathy (DR) by collecting and evaluating available systematic reviews and meta-analysis results. We evaluated the methodological quality using the Measurement Tool to Assess Systematic Reviews (AMSTAR) 2.0, estimated the summary effect size by using the random effects model and calculated the 95% prediction intervals (PIs). Evidence from the included meta-analyses was graded according to established criteria as follows: convincing, highly suggestive, suggestive, weak, or not significant. This umbrella review included 32 meta-analyses of 52 candidate SNPs. The 12 selected meta-analyses were rated as “high,” 2 studies were rated as “moderate,” 11 studies were graded as “low,” and the remaining 7 studies were graded as “critically low” in terms of methodological quality. Carriers of specific genotypes and alleles of the transcription Factor 7-like 2 C/T (TCF7L2 C/T) polymorphism (rs7903146, p < 0.001) might be more susceptible to the occurrence of DR in the homozygous and recessive models, and these associations were supported by “convincing” evidence. Significant associations were also found between interleukin-6 (IL-6) -174 G/C (rs1800795; p < 0.05) or vascular endothelial growth factor (VEGF) polymorphisms (rs2010963, rs699947, rs1570360, rs2010963, rs699947, rs2146323; all p values

Study region: Hetao Irrigation District (Hetao) is the second-largest irrigation district in the Yellow River basin. It is located in a seasonally frozen soil area with shallow groundwater and salinization. These conditions significantly influence the freeze-thaw processes in the soil. Study focus: In this study, a novel water-heat-salt coupling model was developed. An improved soil freezing characteristic curve (SFCC) was proposed to evaluate the effect of salt content on the water-ice phase transition. Additionally, an equilibrium state assumption for the unfrozen soil layers was adopted to describe soil water distribution influenced by shallow groundwater. New hydrological insights for the region: The model effectively captured the spatiotemporal dynamics of water, heat, and salt driven by soil freeze-thaw processes. Besides, it accurately estimated the total water content in the 0–40 cm soil layer, which is the main crop root zone (RMSE < 0.05 cm³/cm³, R² > 0.49). Note that the developed model could accurately simulate soil temperature dynamics, with R² > 0.85 and NSE > 0.77. This study developed a high-efficiency freeze-thaw model for regions like Hetao, with shallow groundwater and severe soil salinization. Compared to complex numerical models, the proposed model has greater potential for regional application.

Water stemming is an efficient method of removing blasting dust by wetting. There is still a lack of methods for rapid optimization of water stemming components with high wettability. Herein, blasting dust was collected from a tunnel in Chongqing (China) to investigate its removal performance by different water stemmings. The two most important components of blasting dust were SiO2 and CaCO3 by characterization analysis. Notably, hydrophilic blasting dust has significantly more SiO2 than hydrophobic blasting dust. The density functional theory calculation predicted the wettability of water stemming containing sucrose fatty acid ester (SE) higher than that of water stemming containing other surfactants. Moreover, the water contact angle and surface tension experiments determined the addition of inorganic salts to the water stemming containing SE could increase its wettability, with the addition of Al3+ giving the best performance. The sink test and water retention experiment further prove that our synthesized water stemming has a good wetting ability on both hydrophobic and hydrophilic blasting dust. The findings of this study advance the development of reliable methods for optimizing water stemming with high wettability for removing the blasting dust.

A convenient and efficient method for undergraduate student experiments involves the one-pot synthesis of phenytoin from benzoin. This method utilized ultrasonic irradiation in the presence of basic catalyst at room temperature and atmospheric pressure, resulting in shortened reaction times, good yields, and excellent reproducibility. By employing a low-cost ultrasonic cleaner for ultrasonic irradiation in student experiments, the need for expensive equipment investment during the teaching process can be minimized. Consequently, this approach is suitable for widespread promotion and application in undergraduate education.

Summary: Glioblastoma (GBM) is a highly lethal malignant brain tumor with poor survival rates, and chemoresistance poses a significant challenge to the treatment of patients with GBM. Here, we show that transketolase (TKT), a metabolic enzyme in the pentose phosphate pathway (PPP), attenuates the chemotherapy sensitivity of glioma cells in a manner independent of catalytic activity. Mechanistically, chemotherapeutic drugs can facilitate the translocation of TKT protein from the cytosol into the nucleus, where TKT physically interacts with XRN2 to regulate the resolution and removal of R-loops. Depletion of TKT leads to increased R-loop accumulation and genome instability, increasing the susceptibility of glioma cells to chemotherapy. In conclusion, our study reveals a non-metabolic function of TKT in regulating R-loop dynamics, genome instability, and chemotherapy sensitivity in gliomas.

Hollow-core anti-resonant optical fiber (HC-ARF) provides solutions for breaking the bottlenecks in areas of high-power transmission and high-efficiency optical waveguide. Other than transporting light wave, HC-ARFs can synergistically combine microfluidics and optics in a single fiber with unprecedented light path length not readily achievable by planar optofluidic configurations. The unique features of strict light confinement, wide transmission band and low transmission loss of HC-ARFs enable high sensing performance with low sample consumption, outcompeting conventional optical assays. In this review, we provide a comprehensive overview of HC-ARFs for label-free molecular sensing. We deliver information on the light propagation mechanism and state-of-the-art structures of HC-ARFs, as well as recent progress in chemical and biomedical sensing mainly covering gas, liquid, DNA and protein sensors along with exosome-based liquid biopsy and cancer cell detection. At the end, challenges and prospects of HC-ARF for sensing applications are discussed.

Sheep play an important role in China’s agricultural development, but they are also potential hosts for many viruses, some of which have been identified as zoonotic pathogens, which may pose a serious threat to social public health and animal husbandry. Therefore, clarifying the characteristics of viruses in sheep will provide an important basis for the study of pathogenic ecology and viral evolution of viruses carried by sheep. We collected nasal and anal swabs from 688 sheep in 22 counties in Shaanxi, Gansu, and Ningxia, China, between January 2022 and July 2023, and utilized next-generation sequencing technology and bioinformatics approaches to identify the viruses in the samples. A total of 38 virus families carried by sheep were identified, including 12 ssRNA (+) virus families, 2 dsRNA virus families, 8 ssDNA (+) virus families, and 18 dsDNA virus families. Among them, Astroviridae, Coronaviridae, Picornaviridae, and Tobaniviridae in RNA virus families and Herpesviridae, Adenoviridae, and Circoviridae in DNA virus families are all viruses that are frequently detected in most ruminants. Alpha and beta diversity results showed that there was no difference in the overall richness and diversity of RNA and DNA viruses among the three provinces (p > 0.05). The evolutionary analysis demonstrated a tight link between the viral members carried by sheep and other ruminant viruses, implying that these viruses may spread across different species of ruminants. This study established a library of RNA and DNA viruses carried by sheep in the Shaanxi-Gansu-Ningxia region, providing an overview of the viruses present in this population. The findings offer valuable data for further research on virus evolution and monitoring in sheep.

Background Evidence on maintenance therapy following frontline induction is sparse in primary light-chain amyloidosis (AL), especially for those who do not undergo autologous haematopoietic stem cell transplantation (ASCT).Methods We enrolled primary AL patients who achieved at least haematologic very good partial response (VGPR) by the 4th month at the frontline from December 2008 to June 2023 at Zhongshan Hospital, Fudan University. Those who followed maintenance therapy were identified as the maintenance group (n = 44), whereas those entering the observational phase were classified as the observational group (n = 24).Results After 7.2(interquartile range, 4.7–18.6) months of maintenance therapy, 9(20.5%), 14(31.8%) and 5 (11.4%) patients achieved improvement in haematologic, cardiac and renal response respectively. Five (11.4%) patients had minimal residual disease (MRD) response conversion from positive to negative based on maintenance therapy. In the observation group, none of the patients had haematologic response improvement, with 3(12.5%) and 1(4.2%) patient showing cardiac and renal response improvement during follow-up.Conclusion This study identified the clinical benefits of maintenance therapy in patients with AL who did not undergo ASCT in real-world practice.

Abstract Objective Transfer RNA-derived fragments (tRFs) are short non-coding RNA (ncRNA) sequences, ranging from 14 to 30 nucleotides, produced through the precise cleavage of precursor and mature tRNAs. While tRFs have been implicated in various diseases, including cancer, their role in lung adenocarcinoma (LUAD) remains underexplored. This study aims to investigate the impact of tRF-Val-CAC-010, a specific tRF molecule, on the phenotype of LUAD cells and its role in tumorigenesis and progression in vivo. Methods The expression level of tRF-Val-CAC-010 was quantified using quantitative real-time polymerase chain reaction (qRT-PCR). Specific inhibitors and mimics of tRF-Val-CAC-010 were synthesized for transient transfection. Cell proliferation was assessed using the Cell Counting Kit-8 (CCK-8), while cell invasion and migration were evaluated through Transwell invasion and scratch assays. Flow cytometry was utilized to analyze cell cycle and apoptosis. The in vivo effects of tRF-Val-CAC-010 on tumor growth and metastasis were determined through tumor formation and metastasis imaging experiments in nude mice. Results The expression level of tRF-Val-CAC-010 was upregulated in A549 and PC9 LUAD cells (P

Abstract METTL3 and METTL14 are traditionally posited to assemble the m6A methyltransferase complex in a stoichiometric 1:1 ratio, modulating mRNA fate via m6A modifications. Nevertheless, recent investigations reveal inconsistent expression levels and prognostic significance of METTL3 and METTL14 across various tumor types, challenging their consistent functional engagement in neoplastic contexts. A pan-cancer analysis leveraging The Cancer Genome Atlas (TCGA) data has identified pronounced disparities in the expression patterns, functional roles, and correlations with tumor burden between METTL3 and METTL14, particularly in esophageal squamous cell carcinoma (ESCC). Knockdown experiments of METTL3 in EC109 cells markedly suppress cell proliferation both in vitro and in vivo, whereas METTL14 knockdown shows a comparatively muted effect on proliferation and does not significantly alter METTL3 protein levels. mRNA sequencing indicates that METTL3 singularly governs the expression of 1615 genes, with only 776 genes co-regulated with METTL14. Additionally, immunofluorescence co-localization studies suggest discrepancies in cellular localization between METTL3 and METTL14. High-performance liquid chromatography–mass spectrometry (HPLC–MS) analyses demonstrate that METTL3 uniquely associates with the Nop56p-linked pre-rRNA complex and mRNA splicing machinery, independent of METTL14. Preliminary bioinformatics and multi-omics investigations reveal that METTL3’s autonomous role in modulating tumor cell proliferation and its involvement in mRNA splicing are potentially pivotal molecular mechanisms. Our study lays both experimental and theoretical groundwork for a deeper understanding of the m6A methyltransferase complex and the development of targeted tumor therapies focusing on METTL3.

Abstract Convergent evolution is central in the origins of multicellularity. Identifying the basis for convergent multicellular evolution is challenging because of the diverse evolutionary origins and environments involved. Haploid Kluyveromyces lactis populations evolve multicellularity during selection for increased settling in liquid media. Strong genomic and phenotypic convergence is observed between K. lactis and previously selected S. cerevisiae populations under similar selection, despite their >100-million-year divergence. We find K. lactis multicellularity is conferred by mutations in genes ACE2 or AIM44, with ACE2 being predominant. They are a subset of the six genes involved in the S. cerevisiae multicellularity. Both ACE2 and AIM44 regulate cell division, indicating that the genetic convergence is likely due to conserved cellular replication mechanisms. Complex population dynamics involving multiple ACE2/AIM44 genotypes are found in most K. lactis lineages. The results show common ancestry and natural selection shape convergence while chance and contingency determine the degree of divergence.

Rice bran, a byproduct of rice processing, holds great nutritional value. However, its application in the food industry is greatly restricted due to its high susceptibility to rancidity and spoilage during storage. Currently, it is primarily used as animal feed with low added value. The presence of lipase and lipoxygenase is the major cause of rapid rancidity of rice bran, and other factors such as water activity, microorganisms and phenolic substances also affect the rancidity reaction. Stabilization treatment of rice bran is a key prerequisite to achieving high-value utilization of the product. This paper provides an overview of the rancidity mechanism of rice bran, the common methods for stabilizing rice bran and their impact on its quality and nutritional characteristics, with a view to providing guidance and reference for the research and development of rice bran as a food-grade raw material.

Abstract In chronic kidney disease (CKD), renal fibrosis is an unavoidable result of various manifestations. However, its pathogenesis is not yet fully understood. Here, we revealed the novel role of Homeobox D10 (HOXD10) in CKD-related fibrosis. HOXD10 expression was downregulated in CKD-related in vitro and in vivo fibrosis models. UUO model mice were administered adeno-associated virus (AAV) containing HOXD10, and HOXD10 overexpression plasmids were introduced into human proximal tubular epithelial cells induced by TGF-β1. The levels of iron, reactive oxygen species (ROS), lipid ROS, the oxidized glutathione/total glutathione (GSSG/GSH) ratio, malonaldehyde (MDA), and superoxide dismutase (SOD) were determined using respective assay kits. Treatment with AAV–HOXD10 significantly attenuated fibrosis and renal dysfunction in UUO model mice by inhibiting NOX4 transcription, ferroptosis pathway activation, and oxidative stress. High levels of NOX4 transcription, ferroptosis pathway activation and profibrotic gene expression induced by TGF-β1/erastin (a ferroptosis agonist) were abrogated by HOXD10 overexpression in HK-2 cells. Moreover, bisulfite sequencing PCR result determined that HOXD10 showed a hypermethylated level in TGF-β1-treated HK-2 cells. The binding of HOXD10 to the NOX4 promoter was confirmed by chromatin immunoprecipitation (ChIP) analysis and dual-luciferase reporter assays. Targeting HOXD10 may represent an innovative therapeutic strategy for fibrosis treatment in CKD.

Abstract Theanine (Thea) is a unique metabolite in tea plants, but its physiological functions remain elusive. A low soil pH increases cadmium (Cd) availability, affecting the quality of tea plant products. In this study, we found that Thea reversed the Cd-induced reduction in free amino acid (FAA) and caffeine (CAF) in the young tea leaves, as well as the down-regulation in the expression of nitrate transporters CsNRT1.2 and CsNRT2.5, and genes responsible for the nitrogen (N) assimilation. We demonstrated that Thea could alleviate Cd-induced oxidative stresses and enhance photosynthesis. Moreover, an ATP-binding cassette (ABC) transporter, CsABCG11.2, could uptake distinct Cd substrates and the five major amino acids in tea plants. Heterologous expression of CsABCG11.2 in yeast indicated a competitive absorption between Cd and Thea in a concentration-dependent pattern. CsABCG11.2-overexpressing Arabidopsis plants exhibited increased sensitivity to Cd due to enhanced Cd concentration, accumulation in the shoots, and reduction in the primary root length. Exogenous application of Thea at environmentally regular levels attenuated the adverse effects of Cd-induced growth inhibition and chlorosis in CsABCG11.2-overexpressing Arabidopsis plants. Knockdown of CsABCG11.2 tea plants significantly lowered Cd levels in young shoots. Our results suggest that Thea plays beneficial roles in alleviating Cd stress directly or indirectly by modulating CsABCG11.2-mediated Cd uptake and translocation within plants.

Summary: China, holding nearly half of the global coal-fired power capacity, must shift from its coal-centric energy system to meet climate and air quality goals. This study explores the optimal utilization of natural gas by evaluating the environmental and economic costs of gas- and coal-fired power using plant-level data and a multidisciplinary modeling approach. We find that gas power has substantially lower air pollution costs (0.77 versus 12.2 cents/kWh) and moderately lower GHG costs (2.8 versus 4.5 cents/kWh), with an average environmental advantage of 12.1 cents/kWh and a social benefit of 10.4 cents/kWh when considering LCOE. The benefits vary spatially with the highest benefits in east-central China. Prioritizing substitution in regions with high environmental benefits could reduce SO2, NOx, and PM emissions by 28%, 15%, and 56%, respectively, offering a 52% higher environmental benefit than existing gas power plans. This study provides quantitative support for gas power development in China.

Summary: The catalytic activity of most epigenetic enzymes requires a metabolite produced by central carbon metabolism as a cofactor or (co-)substrate. The concentrations of these metabolites undergo dynamic changes in response to nutrient levels and environmental conditions, reprogramming metabolic processes and epigenetic landscapes. Abnormal accumulations of epigenetic modulatory metabolites resulting from mutations in metabolic enzymes contribute to tumorigenesis. In this review, we first present the concept that metabolite regulation of gene expression represents an evolutionarily conserved mechanism from prokaryotes to eukaryotes. We then review how individual metabolites affect epigenetic enzymes and cancer development. Lastly, we discuss the advancement of and opportunity for therapeutic targeting of metabolite-epigenetic regulation in cancer therapy.

Cover crops are one of the climate-smart agricultural practices used to increase soil organic carbon (SOC) sequestration. However, the SOC sequestration potential and underlying mechanisms under different cover crops, especially in orchard agroecosystems, have not been fully elucidated. Here, we investigated three orchards in China using SOC fractionation methods, high-throughput sequencing, and biomarker analysis. Our objectives were to determine the effect of cover crops on the physical fractions and chemical compositions of SOC, as well as on microbial properties, and to clarify why legume and non-legume cover crops sequester SOC differently. The results showed different increases in SOC between legume and non-legume cover crops (+38% vs. +16%) compared with those in the control plots without cover crops. Legume cover crops increased mineral-associated and particulate organic carbon, whereas non-legume cover crops increased mineral-associated organic carbon only. These differences were attributed to their distinct effects on microbial SOC transformation pathways. Legume cover crops positively impacted microbial pathways by increasing the availability of soil substrates and nitrogen, such as dissolved organic carbon (+84%), O-alkyl carbon (+18%), and ammonium nitrogen (+42%). These results were supported by the increases in carbon and nitrogen enzyme activities, microbial community diversity indices, the abundance of dominant fungal taxa (Sordariomycetes), microbial biomass carbon (+105%), and microbial necromass carbon (+47%). Non-legume cover crops might have induced microbial nitrogen starvation, decreasing the efficiency of microbial pathways, as evidenced by the low β-glucosidase to β-N-acetylglucosaminidase ratios (−7%) and the lack of significant changes in the bacterial Shannon index or microbial necromass carbon. In addition, redundancy analysis revealed that enzyme activity, the microbial community, and microbial necromass carbon collectively dominated the changes in the SOC physical fraction. Site-specific soil properties such as soil texture and nitrogen availability were important factors influencing SOC sequestration under cover crops. Our study provides essential insights for optimizing cover crop management to increase SOC sequestration in orchard agroecosystems.

Summary: Background: This was a multicenter, single-arm dose-ranging phase 2 study aimed to assess the efficacy and safety of LY01610, a liposomal irinotecan, at various doses for patients with relapsed small cell lung cancer (SCLC). Methods: This study (NCT04381910) enrolled patients with relapsed SCLC at 10 hospitals across China, who have failed with previous platinum-based treatments. LY01610 was administered at doses of 60 mg/m2, 80 mg/m2, and 100 mg/m2. Primary endpoints were investigator-assessed objective response rate (ORR) and investigator-assessed duration of response (DoR). Secondary endpoints included investigator-assessed disease control rate (DCR), investigator-assessed progression-free survival (PFS), overall survival (OS), and safety. Findings: From September 3, 2020 to March 3, 2022, a total of 66 patients were enrolled, with 6, 30, and 30 allocated to the 60 mg/m2, 80 mg/m2, and 100 mg/m2 dose groups, respectively, with 68% (45/66) having a chemotherapy-free interval

Objective In this study, we aimed to explore the potential association between COVID-19 infection, hospitalization, severe COVID-19, and erection dysfunction (ED) using the two-sample Mendelian randomization (MR) method. Methods Data pertaining to COVID-19 were extracted from the latest version of the COVID-19 Host Genetics Initiative genome-wide association study (GWAS) meta-analyses (Round 7, April 2022), and outcome data were obtained from the Open GWAS database. We applied various MR analysis methods, including the inverse variance weighted method, weighted median method, and MR-Egger regression. Results Our investigation revealed a negative causal association between COVID-19 hospitalization and ED (total testosterone levels: beta = −0.026; 95% confidence interval: −0.049 to −0.001). However, no evidence supported causal relationships between COVID-19 infection, hospitalization for COVID-19, or severe COVID-19 and other ED risk factors. Conclusion The results of this comprehensive MR analysis suggest a negative causal link between COVID-19 hospitalization and total testosterone levels. Nonetheless, COVID-19 (comprising infection, hospitalization, and severe illness) may not directly correlate with an increased risk of ED. These findings imply that COVID-19 may exert a distinct impact on ED through indirect pathways.

Abstract Bovine viral diarrhea virus (BVDV) is considered to be the most common agent of severe diarrhea in cattle worldwide, causing fever, diarrhea, ulcers, and abortion. Bovine herpesvirus 1 (BoHV-1) is also a major bovine respiratory disease agent that spreads worldwide and causes extensive damage to the livestock industry. Recombinase polymerase amplification (RPA) is a novel nucleic acid amplification method with the advantages of high efficiency, rapidity and sensitivity, which has been widely used in the diagnosis of infectious diseases. A dual RPA assay was developed for the simultaneous detection of BVDV and BoHV-1. The assay was completed at a constant temperature of 37 °C for 30 min. It was highly sensitive and had no cross-reactivity with other common bovine viruses. The detection rate of BVDV RPA in clinical samples (36.67%) was higher than that of PCR (33.33%), the detection rate of BoHV-1 RPA and PCR were equal. Therefore, the established dual RPA assay for BVDV and BoHV-1 could be a potential candidate for use as an immediate diagnostic.

Abstract Background The pollution of soil by heavy metals, particularly Cd, is constitutes a critical international environmental concern. Willow species are renowned for their efficacy in the phytoremediation of heavy metals owing to their high Cd absorption rate and rapid growth. However, the mechanisms underlying microbial regulation for high- and low-accumulating willow species remain poorly understood. Therefore, we investigated the responses of soil and rhizosphere microbial communities to high- and low-Cd-accumulating willows and Cd contamination. We analyzed soil properties were analyzed in bulk soil (SM) and rhizosphere soil (RM) planted with high-accumulating (H) and low-accumulating (L) willow species. Results Rhizosphere soil for different willow species had more NH4+ than that of bulk soil, and RM-H soil had more than RM-L had. The available phosphorus content was greater in hyper-accumulated species than it was in lower-accumulated species, especially in RM-H. Genome sequencing of bacterial and fungal communities showed that RM-L exhibited the highest bacterial diversity, whereas RM-H displayed the greatest richness than the other groups. SM-L exhibited the highest diversity and richness of fungal communities. Ralstonia emerged as the predominant bacterium in RM-H, whereas Basidiomycota and Cercozoa were the most enriched fungi in SM-H. Annotation of the N and C metabolism pathways revealed differential patterns: expression levels of NRT2, NarB, nirA, nirD, nrfA, and nosZ were highest in RM-H, demonstrating the effects of NO3 -and N on the high accumulation of Cd in RM-H. The annotated genes associated with C metabolism indicated a preference for the tricarboxylic pathway in RM-H, whereas the hydroxypropionate-hydroxybutyrate cycle was implicated in C sequestration in SM-L. Conclusions These contribute to elucidation of the mechanism underlying high Cd accumulation in willows, particularly in respect of the roles of microbes and N and C utilization. This will provide valuable insights for repairing polluted soil using N and employing organic acids to improve heavy metal remediation efficiency.

Abstract Enhancing immune response activation through the synergy of effective antigen delivery and immune enhancement using natural, biodegradable materials with immune-adjuvant capabilities is challenging. Here, we present NAPS L.p that can activate the Toll-like receptor 4 (TLR4) pathway, an amphiphilic exopolysaccharide, as a potential self-assembly adjuvant delivery platform. Its molecular structure and unique properties exhibited remarkable self-assembly, forming a homogeneous nanovaccine with ovalbumin (OVA) as the model antigen. When used as an adjuvant, NAPS L.p significantly increased OVA uptake by dendritic cells. In vivo imaging revealed prolonged pharmacokinetics of NAPS L. p -delivered OVA compared to OVA alone. Notably, NAPS L.p induced elevated levels of specific serum IgG and isotype titers, enhancing rejection of B16-OVA melanoma xenografts in vaccinated mice. Additionally, NAPS L.p formulation improved therapeutic effects, inhibiting tumor growth, and increasing animal survival rates. The nanovaccine elicited CD4+ and CD8+ T cell-based immune responses, demonstrating the potential for melanoma prevention. Furthermore, NAPS L.p -based vaccination showed stronger protective effects against influenza compared to Al (OH)3 adjuvant. Our findings suggest NAPS L.p as a promising, natural self-adjuvanting delivery platform to enhance vaccine design across applications.

Abstract Background Pelvic floor myofascial pain is one of the pelvic floor dysfunction diseases disturbing women after delivery. There is a lack of objective standardization for the diagnosis of pelvic floor myofascial pain due to the various symptoms and the dependence on the palpating evaluation. Ultrasound imaging has the advantages of safety, simplicity, economy and high resolution, which makes it an ideal tool for the assistant diagnosis of pelvic floor myofascial pain and evaluation after treatment. Methods This is a retrospective case-control study including women accepting evaluation of pelvic floor function at 6 weeks to 1 year postpartum. They were divided into pelvic floor myofascial pain group and normal control group. A BCL 10–5 biplane transducer was applied to observed their puborectalis. The length, minimum width, area, deficiency, deficiency length, deficiency width, deficiency area, rate of deficiency area, local thickening,angle between the tendinous arch of levator ani muscle and puborectalis of corresponding puborectalis in different groups were observed and measured. Results A total of 220 postpartum women participated in the study, with 77 in the pelvic floor myofascial pain group and 143 in the normal control group. The Intraclass correlation coefficient value was over 0.750, and Kappa ranged from 0.600 to 0.800. puborectalis deficiency (adjusted odds ratio = 11.625, 95% confidence interval = 4.557–29.658) and focal thickening (adjusted odds ratio = 16.891, 95% confidence interval = 1.819–156.805) were significantly associated with higher odds of having postpartum pelvic floor myofascial pain. Grayscale or the angle between the arch tendineus levator ani and puborectalis measurements on the pain side tended to be smaller than on the non-pain side in patients with unilateral puborectalis or iliococcygeus pain (P

Abstract Doxorubicin has been used extensively as a potent anticancer agent, but its clinical use is limited by its cardiotoxicity. However, the underlying mechanisms remain to be fully elucidated. In this study, we tested whether NADPH oxidase 2 (Nox2) mediates cardiac sympathetic nerve terminal abnormalities and myocyte autophagy, resulting in cardiac atrophy and dysfunction in doxorubicin-induced heart failure. Nox2 knockout (KO) and wild-type (WT) mice were randomly assigned to receive a single injection of doxorubicin (15 mg/kg, i.p.) or saline. WT doxorubicin mice exhibited the decreases in survival rate, left ventricular (LV) wall thickness and LV fractional shortening and the increase in the lung wet-to-dry weight ratio 1 week after the injections. These alterations were attenuated in Nox2 KO doxorubicin mice. In WT doxorubicin mice, myocardial oxidative stress was increased, myocardial noradrenergic nerve fibers were reduced, myocardial expression of PGP9.5, GAP43, tyrosine hydroxylase and norepinephrine transporter was decreased, and these changes were prevented in Nox2 KO doxorubicin mice. Myocyte autophagy was increased and myocyte size was decreased in WT doxorubicin mice, but not in Nox2 KO doxorubicin mice. Nox2 mediates cardiac sympathetic nerve terminal abnormalities and myocyte autophagy—both of which contribute to cardiac atrophy and failure after doxorubicin treatment.

Objective This study was based on the network pharmacology to explore the mechanisms whereby Tribulus terrestris affects vitiligo. Methods The screening criteria for oral bioavailability (OB) and drug-likeness (DL) were set as OB≥30% and DL≥0.18, respectively. The databases of Traditional Chinese Medicine Systems Pharmacology and analysis platforms of OMIM, Swiss Target Prediction and GeneCards were used to screen out target genes of main active ingredients of Tribulus terrestris and construct an "active ingredients-target" network using Cytoscape 3.9.1 software. Then the target genes of the main active ingredients of Tribulus terrestris and the target genes of vitiligo were intersected to construct a "disease-pathway-target-component-drug" network. In addition, the intersection targets were respectively imported into the STRING platform to construct Protein-Protein Interaction (PPI) Networks, and into the DAVID database for GO and KEGG pathway enrichment analyses. The structure of small molecules of key drug components and vitiligo-related protein structure were searched on PubChem and PBD. After setting up receptors and ligands, the molecular docking of these two was performed. Results Through screening, we identified 12 active ingredients, including kaempferol, terrestramide, isorhamnetin, sitosterol, which possibly affect 71 targets. PPI network analysis showed ten major targets, including AKT1, TNF, ESR1, PPARG, HPGDS, CASP3, and PTGS2. These targets were involved in many biological processes, such as apoptosis, peptide serine phosphorylation, and cell response to reactive oxygen species, through various signaling pathways, including apoptosis, tumor necrosis factor and reactive oxygen species signaling. Molecular docking results showed that the main active components such as kaverol and isorhamnetin were stably bound to the core targets, such as AKT1, TNF and ESR1, the core components regulating key targets. Conclusion Tribulus terrestris may improve vitiligo through regulating inflammation, apoptosis, immune function and oxidative stress.

Railway turnout is a critical railway infrastructure that guides trains in switching tracks. Over time, uneven rail wear can lead to switch rail reduction value (SRRV) deviation, a typical structural defect that compromises turnout functionality and jeopardizes train operation safety. Current SRRV deviation detection methods rely primarily on inefficient manual inspections, making it difficult to ensure operational safety. To address this issue, the study carried out a comprehensive investigation combining numerical and experimental analyses. First, a rigid–flexible coupled dynamics model of a vehicle-turnout system was developed to analyze the wheel–rail dynamic interaction forces and contact relationships under various SRRV deviation conditions. The results revealed that SRRV deviation significantly affects both wheel–rail interaction forces and the turnout structural irregularity wavelength. Thus, based on discrete wavelet transform (DWT), a wheel–rail force trend component was derived that can effectively analyze the turnout structural irregular wavelength, and the mapping relationship between SRRV deviation and the wheel–rail force trend component was then established. Finally, an efficient and accurate method for identifying SRRV deviation based on wheel–rail force trend component was proposed and validated using field-measured data from trains passing through turnouts. This study contributes to the timely detection of track defects, helping to prevent safety incidents during train operations.