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Super-enhancers (SEs) govern the expression of genes defining cell identity. However, the dynamic landscape of SEs and their critical constituent enhancers involved in skeletal muscle development remains unclear. In this study, using pig as a model, we employed CUT&Tag to profile the enhancer-associated histone modification marker H3K27ac in skeletal muscle across two prenatal and three postnatal stages and investigated how SEs influence skeletal muscle development. We identified three SE families with distinct temporal dynamics: continuous (Con, 397), transient (TS, 434), and de novo (DN, 756). These SE families are associated with different temporal gene expression trajectories, biological functions, and DNA methylation levels. Notably, several lines of evidence suggest a potential prominent role of Con SEs in regulating porcine muscle development and meat traits. To pinpoint key cis -regulatory units in Con SEs, we developed an integrative approach that leverages information from eRNA annotation, GWAS signals and high-throughput capture STARR-seq experiments. Within Con SEs, we identified 20 candidate critical enhancers with meat and carcass-associated DNA variations that affect enhancer activity and inferred their upstream TFs and downstream target genes. As a proof of concept, we experimentally validated the role of one such enhancer and its potential target gene during myogenesis. Our findings reveal the dynamic regulatory features of SEs in skeletal muscle development and provide a general integrative framework for identifying critical enhancers underlying the formation of complex traits., (Published by Cold Spring Harbor Laboratory Press.)

Organic anion transporting polypeptides (OATP, gene symbol SLCO ) are well-recognized key determinants for the absorption, distribution, and excretion of a wide spectrum of endogenous and exogenous compounds including many antineoplastic agents. It was therefore proposed as a potential drug target for cancer therapy. In our previous study, it was found that low-dose X-ray and carbon ion irradiation both upregulated the expression of OATP family member OATP1A2 and in turn, led to a more dramatic killing effect when cancer cells were cotreated with antitumor drugs such as methotrexate. In the present study, the underlying mechanism of the phenomenon was explored in breast cancer cell line MCF-7. It was found that the nonreceptor tyrosine kinase v-YES-1 Yamaguchi sarcoma viral oncogene homolog 1 (YES-1) was temporally coordinated with the change of OATP1A2 after irradiation. The overexpression of YES-1 significantly increased OATP1A2 both at the mRNA and protein level. The signal transducer and activator of transcription 3 (STAT3) pathway is likely the downstream target of YES-1 because phosphorylation and nuclear accumulation of STAT3 were both enhanced after overexpressing YES-1 in MCF-7 cells. Further investigation revealed that there are two possible binding sites of STAT3 localized at the upstream sequence of SLCO1A2 , the encoding gene of OATP1A2. Electrophoretic mobility shift assay and chromatin immunoprecipitation analysis suggested that these two sites bound to STAT3 specifically and the overexpression of YES-1 significantly increased the association of the transcription factor with the putative binding sites. Finally, inhibition or knockdown of YES-1 attenuated the induction effect of radiation on the expression of OATP1A2. SIGNIFICANCE STATEMENT: The present study found that the effect of X-rays on v-YES-1 Yamaguchi sarcoma viral oncogene homolog 1 (YES-1) and organic anion transporting polypeptides (OATP)1A2 was temporally coordinated. YES-1 phosphorylates and increases the nuclear accumulation of signal transducer and activator of transcription 3, which in turn binds to the upstream regulatory sequences of SLCO1A2 , the coding gene for OATP1A2. Hence, inhibitors of YES-1 may suppress the radiation induction effect on OATP1A2., (Copyright © 2024 by The American Society for Pharmacology and Experimental Therapeutics.)

Conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) by ten-eleven translocation (TET) family proteins leads to the accumulation of 5hmC in the central nervous system; however, the role of 5hmC in the postnatal brain and how its levels and target genes are regulated by TETs remain elusive. We have generated mice that lack all three Tet genes specifically in postnatal excitatory neurons. These mice exhibit significantly reduced 5hmC levels, altered dendritic spine morphology within brain regions crucial for cognition, and substantially impaired spatial and associative memories. Transcriptome profiling combined with epigenetic mapping reveals that a subset of genes, which display changes in both 5hmC/5mC levels and expression patterns, are involved in synapse-related functions. Our findings provide insight into the role of postnatally accumulated 5hmC in the mouse brain and underscore the impact of 5hmC modification on the expression of genes essential for synapse development and function., (© 2024. Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences.)

To tackle the clinical challenge of noninvasively assessing immunotherapy efficacy in patients, here we used positron emission tomography (PET) with 68 Ga-grazytracer, which targets granzyme B, a crucial effector molecule secreted by activated CD8 + T cells. In this phase 1/2 clinical trial (NCT05000372) involving a diverse cohort of 24 patients with solid tumors and lymphomas who received immunotherapies, including immune checkpoint inhibitors (either alone or with chemotherapies) and chimeric antigen receptor-T cell therapy, we examined the in vivo behaviors of 68 Ga-grazytracer. Primary endpoints were safety, biodistribution, granzyme B specificity, and the predictive utility of 68 Ga-grazytracer, while secondary endpoint was the relationship between 68 Ga-grazytracer uptake and tumor immune phenotype. 68 Ga-grazytracer exhibited a safe profile and specifically targeted granzyme B in patients. 68 Ga-grazytracer PET showed superior predictive value for short-term prognosis and progression-free survival than those of conventional assessment criteria, including RECIST 1.1 and PERCIST. Moreover, the uptake of 68 Ga-grazytracer in tumors was significantly higher in those with a "non-desert" immune phenotype than those with an immune "desert" phenotype, thereby meeting the primary and secondary endpoints of this trial. Collectively, we successfully visualized CD8 + T cell effector function in humans using 68 Ga-grazytracer PET, offering insights for enhancing immunotherapy assessment, patient stratification and treatment planning., (© 2024. The Author(s).)

In this work, three alkoxy-substituted quinoxaline core-based small-molecule acceptors (BQO-F, BQDO-F, and BQDO-Cl) are developed to elucidate the impact of ethoxy substituents on the physicochemical and photoelectric properties. Comparative analysis reveals that dialkoxy-substituted BQDO-F has a more planar molecular skeleton, a red-shifted absorption spectrum, upshifted energy levels, stronger crystallinity, and reduced energetic disorder compared to the monoalkoxy-substituted BQO-F. Although the replacement of fluorine atoms with chlorine atoms on the end-capped units of BQDO-F leads to a bathochromically shifted absorption spectrum, the resulting molecule BQDO-Cl shows worse π-π packing order compared to BQDO-F. Benefiting from the more favorable active layer morphology and improved carrier dynamics, the PBDB-T:BQDO-F-based organic solar cell achieves a much higher power conversion efficiency (PCE) of 16.41% compared to that of 14.48% obtained in the BQO-F-based device. In comparison with the BQDO-F-based device, the higher voltage loss of the BQDO-Cl-based device results in a lower PCE of 15.89%. The results clarify the effects of ethoxy substituents and end-capped substitutions of quinoxaline core-based small-molecule acceptors on efficient organic solar cells.

Purpose: Immunohistochemical staining of programmed death-ligand 1 (PD-L1) in tumor biopsies acquired through invasive procedures is routinely employed in clinical practice to identify patients who are most likely to benefit from anti-programmed cell death protein 1 (PD-1) therapy. Nevertheless, PD-L1 expression is observed in various cellular subsets within tumors and their microenvironments, including tumor cells, dendritic cells, and macrophages. The impact of PD-L1 expression across these different cell types on the responsiveness to anti-PD-1 treatment is yet to be fully understood., Methods: We synthesized polymer-based lysosome-targeting chimeras (LYTACs) that incorporate both PD-L1-targeting motifs and liver cell-specific asialoglycoprotein receptor (ASGPR) recognition elements. Small-animal positron emission tomography (PET) imaging of PD-L1 expression was also conducted using a PD-L1-specific radiotracer 89 Zr-αPD-L1/Fab., Results: The PD-L1 LYTAC platform was capable of specifically degrading PD-L1 expressed on liver cancer cells through the lysosomal degradation pathway via ASGPR without impacting the PD-L1 expression on host cells. When coupled with whole-body PD-L1 PET imaging, our studies revealed that host cell PD-L1, rather than tumor cell PD-L1, is pivotal in the antitumor response to anti-PD-1 therapy in a mouse model of liver cancer., Conclusion: The LYTAC strategy, enhanced by PET imaging, has the potential to surmount the limitations of knockout mouse models and to provide a versatile approach for the selective degradation of target proteins in vivo. This could significantly aid in the investigation of the roles and mechanisms of protein functions associated with specific cell subsets in living subjects., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To explore the effects of a single dose of uridine adenosine tetraphosphate (Up 4 A) administered through the tail vein, on the blood pressure of mice., Methods: The mice were separated into three groups: the Up 4 A group, the norepinephrine (NA) group, and the α, β-methylene adenosine triphosphate (α, β-meATP) group. Each group of mice were injected drugs through the tail vein at 1, 3, 10, and 30 nmol/kg doses in an ascending order. Additionally, six mice were injected Up 4 A through the tail vein at 20, 40, 60, and 80 nmol/kg doses in an ascending order. The administration intervals for each dose were 20 min., Results: Mice in these groups experienced a rapid increase in blood pressure, reaching its peak within 10 s after drug administration. It took approximately 120 s for the blood pressure to return to baseline levels after the administration of the drugs in both the NA and α, β-meATP groups. After higher doses of Up 4 A were administered to the mice, their blood pressure exhibited biphasic changes. Initially, blood pressure of the mice rapidly dropped to a minimum within 10 s, then rose rapidly to a peak within 30 s. Subsequently, it gradually declined, taking around 10 min to return to the levels before the drug administration., Conclusion: Compared to NA and α, β-meATP, Up 4 A, which contains purine and pyrimidine components, displayed a weaker blood pressure-elevating potency. Through its corresponding structure, Up 4 A exerted vasodilatory and vasoconstrictive effects throughout the entire experiment resulting in biphasic changes in blood pressure., (© 2024. The Author(s).)

Chaenomeles speciosa (Sweet) Nakai ( C. speciosa ) is a traditional Chinese herbal medicine that possesses not only abundant nutritional value but also significant medicinal properties. The extracts of C. speciosa fruits effectively reduce urate levels, but the specific chemical constituents responsible for this effect in C. speciosa fruits are still unknown. Therefore, this study aims to investigate and analyze the structure-activity relationships of these constituents to better understand their ability to lower uric acid. Activity-guided fractionation and purification processes were used to isolate compounds with xanthine oxidase (XO) inhibitory activity from C. speciosa fruits, resulting in three extracts: petroleum ether, ethyl acetate, and n -butanol. The ethyl acetate and n -butanol fractions showed strong activity and underwent further separation and purification using chromatographic techniques. Twenty-four compounds were isolated and identified, with nine showing potent activity, including chlorogenic acid, methyl chlorogenate, butyl chlorogenate, ethyl chlorogenate, cryptochlorogenic acid methyl ester, caffeic acid, p -coumaric acid, benzoic acid and protocatechuic acid. The docking analysis showed that these compounds interacted with amino acid residues in the active site of XO through hydrogen bonding and hydrophobic interactions. These findings suggest that these compounds help reduce uric acid in C. speciosa , supporting further investigation into their mechanism of action.

Nilaparvata lugens is a notorious rice pest causing significant annual yield and economic losses. The use of entomopathogenic fungi offers a promising and eco-friendly approach to sustainable pest management programs. However, research in this area is currently limited to a few specific types of insects and other arthropods. This study aimed to analyze the biocontrol potential of Lecanicillium attenuatum against N. lugens. Bioassays showed that L. attenuatum 3166 induced >80% mortality in N. lugens following 7 d exposure. Greenhouse and field investigations demonstrated that L. attenuatum 3166 application leads to a substantial reduction in N. lugens populations. Under greenhouse conditions, fluorescence was detected in GFP-labeled L. attenuatum 3166 hyphae enveloping the bodies of N. lugens. In field trials, L. attenuatum 3166 treatment exhibited a control efficacy of up to 68.94% at 14 d post-application, which was comparable to that of the commercial entomopathogenic fungal agent. Genomic sequencing of L. attenuatum 3166 revealed a comprehensive array of genes implicated in its infestation and lethality. Further, the transcriptome sequencing analysis highlighted the elevated expression levels of genes encoding proteases, chitinases, cutinases, and phospholipases. Our findings highlight the potential of L. attenuatum 3166 as an effective biological control agent against N. lugens., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Soybean is a food crop with strong selenium (Se) enrichment ability. Selenium nanoparticles (SeNPs) are a low-toxic Se source. To develop strategies in SeNPs biofortification of soybean and natto, the effects of Se enrichment and natto fermentation on selenoamino acids, mineral elements, free amino acids, γ-polyglutamic acid, nattokinase, and bioaccessibility were investigated. Soybean grains were able to convert SeNPs into selenomethionine (SeMet). Selenium enrichment and natto fermentation influenced the enrichment and distribution of multi-elements in soybean, as well as the composition of free and bound amino acids. Selenium enrichment had no significant effect on the bioaccessibility of amino acids. After natto fermentation, the bioaccessibility of SeMet, Fe, Mn, Cu, and Zn in the gastrointestinal tract increased significantly by 10.1-18.9 %. These findings indicate that SeNPs can enhance the Se content of soybean grains, and natto fermentation can further improve the nutritional quality of Se-enriched soybean., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

With the increasing shortage of water resources and the aggravation of water pollution, solar-driven interfacial steam generation (SISG) technology has garnered considerable attention because of its low energy consumption, simple operation, and environmental friendliness. The popular multi-layer SISG evaporator is composed of two basic structures: a photothermal layer and a support layer. Herein, the support layer underlies the photothermal layer and carries out thermal management, supports the photothermal layer, and transports water to the evaporation interface to improve the stability of the evaporator. While most research focuses on the photothermal layer, the support layer is typically viewed as a supporting object for the photothermal layer. This review focuses on the support layer, which is relatively neglected in evaporator development. It summarizes existing progress in the field of multi-layer interface evaporators, based on various polymers and biomaterials, along with their advantages and disadvantages. Specifically, mainly polymer-based support layers are reviewed, including polymer foams, gels, and their corresponding functional materials, while biomaterial support layers, including natural plants, carbonized biomaterials, and other innovation biomaterials are not. Additionally, the corresponding structure design strategies for the support layer were also involved. It was found that the selection and optimal design of the substrate also played an important role in the efficient operation of the whole steam generation system. Their evolution and refinement are vital for advancing the sustainability and effectiveness of interfacial evaporation technology. The corresponding potential future research direction and application prospects of support layer materials are carefully presented to enable effective responses to global water challenges.

When IL-1 receptor antagonist (IL-1rn) is knocked out, mice have shown strain background dependent and major QTL regulated susceptibility to spontaneously inflammatory arthritis disease (SAD). The impact on bone properties resulting from the interactions of IL-1rn, genomic background strains, and the QTL locus, is unknown. Bone properties in the four specifically bred mouse strains with mutation of IL-1rn and variations in genomic components were investigated with high-resolution MicroCT and genomic analytical tools. Two congenic mouse strains were also measured to evaluate the influence on bone properties by a QTL in the region in chromosome 1. Our results reveal that several bone phenotypes, including bone mineral density (BMD), bone volume, tibial length, and cortical thickness of the tibia are different between wild type and IL-1rn knockout mice in both Balb/c and DBA/1 backgrounds, but IL-1rn knockout affects BMD differently between the two mouse strains. The absence of IL-1rn decreases BMD in Balb/c mice but increases BMD in DBA/1 -/- mice compared to their respective wild type counterparts. A QTL transferred from the Balb/c genetic background which affects arthritis in congenic strains appears to also regulate BMD. While several genes, including Ctsg and Prg2, may affect BMD, Ifi202b is the most favored candidate gene for regulating BMD as well as SAD. In conclusion, the previously mentioned bone phenotypes are each influenced in different ways by the loss of IL-1ra when considered in mice from varying genomic backgrounds., (© 2024. The Author(s).)

Selenium nanoparticles (SeNPs) enhance the immune response as adjuvants, increasing the efficacy of viral vaccines, including those for COVID-19. However, the efficiency of mucosal SeNPs in boosting vaccine-induced protective immunity against tuberculosis remains unclear. Therefore, this study aims to investigate whether the combination of SeNPs with the AH antigen (Ag85A-HspX) can boost respiratory mucosal immunity and thereby enhance the protective effects against tuberculosis. We synthesized SeNPs and assessed their impact on the immune response and protection against Mycobacterium bovis (M. bovis) as a mucosal adjuvant in mice, administered intranasally at a dose of 20 µg. SeNPs outperformed polyinosinic-polycytidylic acid (Poly IC) in stimulating the maturation of bone marrow-derived dendritic cells (BMDCs), which enhanced antigen presentation. SeNPs significantly activated and proliferated tissue-resident memory T cells (T RMs ) and effector CD4 + T cells in the lungs. The vaccines elicited specific antibody responses in the respiratory tract and stimulated systemic Th1 and Th17 immune responses. Immunization with AH and SeNPs led to higher levels of mucosal secretory IgA in bronchoalveolar lavage fluid (BALF) and secretory IL-17 in splenocytes. Moreover, SeNPs immunized mice showed reduced M. bovis infection loads and inflammatory lesions in the lungs post-challenge. Notably, immunization with AH and SeNPs significantly reduced bacterial load in the lungs, achieving the lowest levels compared to all other tested groups. This study calls for pre-clinical investigation of AHB-SeNPs as an anti-bovine tuberculosis vaccine and for exploring its human vaccine potential, which is anticipated to aid in the development of innovative vaccines or adjuvants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To evaluate the efficacy and safety of semaglutide combined with metformin in treating type 2 diabetes mellitus (T2DM) patients who are overweight or obese., Methods: We conducted a comprehensive search across multiple databases including Wanfang, CNKI, Chinese Biomedical Literature, VIP, Embase, PubMed, Cochrane Library, and Web of Science. Studies were screened to include randomized controlled trials (RCTs) comparing semaglutide combined with metformin versus metformin alone in T2DM patients with obesity or who are overweight. Primary outcomes included glycemic efficacy and body mass index (BMI). Secondary endpoints included pancreatic function, blood lipids, and incidence of adverse effects. Pooled and sensitivity analyses were performed, and risk of bias was assessed., Results: Ten studies met the inclusion criteria, all involving oral semaglutide. Compared with placebo, semaglutide with metformin significantly reduced fasting blood glucose (SMD: -0.94; 95% CI: -1.53 to -0.35) and 2-hour postprandial glucose (SMD: -0.97; 95% CI: -1.44 to -1.50; P<0.0001). It also lowered HbA1c levels (SMD: -1.13; 95% CI: -1.85 to -0.42; P<0.001) and BMI (SMD: -1.08; 95% CI: -1.47 to -0.69). Improvements were also noted in HOMA-IR and blood lipid levels. However, there were no significant differences in the incidence of adverse reactions, such as hypoglycemia, gastrointestinal reactions, and dizziness and headache between the two groups (all P>0.05)., Conclusion: Treatment with semaglutide combined with metformin significantly improved glycemic control, insulin resistance, weight, BMI, and lipid profiles in patients with T2DM who are overweight or obese., Competing Interests: None., (AJTR Copyright © 2024.)

Acteoside (ACT) was the main bioactive components in phenylethanoid glycosides of Cistanche tubulosa. Currently, the development of an efficient method for selectively separating ACT was crucial. Consequently, yolk-shell magnetic mesoporous carbon (YSMMC) was synthesized as a nanofiller to prepare molecularly imprinted membranes (ACT-MIMs) with instant noodles-like structure for selectively separating ACT. The numerous YSMMC were moved to the upper surface of ACT-MIMs by magnetic guidance and constructed the instant noodles-like structure in ACT-MIMs. The instant noodle-like structure increased the surface roughness of ACT-MIMs, which was conducive to improving the effective imprinted interface, increasing the selectivity of ACT-MIMs. In addition, the instant noodle-like structure had dendritic interleaved pathways in ACT-MIMs. The dendritic interleaved pathways can intercept ACT through ACT-MIMs, enhancing the permselectivity of ACT-MIMs. The prepared YSMMC possessed the dendritic shell and interlayer cavity structure can provide a great accommodation space, improving the rebinding capacities of ACT-MIMs. The high permselectivity (14.49), remarkable selectivity (7.52), and excellent rebinding capacity (120.48 mg/g) were achieved for the prepared ACT-MIMs. Thus, the design of ACT-MIMs with the instant noodles-like structure were valuable for selectively separating of bioactive components., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The uncontrolled lithium (Li) dendrite growth significantly impacts the safety performance of polymer separators. To mitigate this growth, this study introduces Si 3 N 4 into sulfonated poly(ether Ether Ketone) (SPEEK) and prepares Si 3 N 4 /SPEEK composite separators via electrospinning. At the interface between the Si 3 N 4 /SPEEK separator and the Li anode, the Si nanowires that form impede Li dendrite growth, thereby enhancing the electrochemical performance of lithium-ion batteries (LIBs). The Li deposition test of the 10 % Si 3 N 4 /SPEEK separator can operate for 1000 h without short-circuiting. Additionally, the LiFePO 4 ||Li cell with the 10 % Si 3 N 4 /SPEEK separator shows improved initial discharge capacity (157.8 mAh g -1 at 1C) and superior rate performance (125 mAh g -1 at 10C). Moreover, the nano-scale Si 3 N 4 endows the separator with robust thermal and mechanical properties. The FLIR observations reveal that the 10 % Si 3 N 4 /SPEEK separator maintains uniform thermal distribution and structural integrity even at 300 °C, ensuring safe battery operation at high temperatures. The additional load of the 10 % Si 3 N 4 /SPEEK separator can reach 10.2 mN, which enhances the puncture resistance of the separator. This work provides a solid approach for the application of SPEEK as a high-safety and high-rate LIB separator., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The construction of heterojunctions can reduce the energy barrier for the oxygen evolution reaction (OER), which is crucial for the design of efficient electrocatalysts. A novel OER electrocatalyst, composed of g-C 3 N 4 -supported NiFeP spherical nanoclusters, was successfully synthesized using a simple hydrothermal method and a gas-phase precipitation method. Benefiting from its unique spherical nanocluster structure and strong electronic interactions among Ni, Fe, and P, the catalyst exhibited outstanding performance under alkaline conditions, with an overpotential of only 232 mV at a current density of 10 mA cm -2 and a Tafel slope of 103 mV dec -1 . Additionally, the electrical resistance of NiFeP/g-C 3 N 4 (R ct  = 5.1 Ω) was much lower than that of NiFeP (R ct  = 10.8 Ω) and layered g-C 3 N 4 (R ct  = 44.8 Ω). The formation of a Schottky barrier heterojunction efficiently reduced electron transfer impedance during the OER process, accelerating the electron transfer from g-C 3 N 4 to NiFeP, enhancing the carrier concentration, and thereby improving the OER activity. Moreover, The robust g-C 3 N 4 chain-mail protects NiFeP from adverse reaction environments, maintaining a balance between catalytic activity and stability. Furthermore, ab initio molecular dynamics (AIMD) and density functional theory (DFT) were conducted to explore the thermal stability and internal electron transfer behavior of the cluster heterojunction structure. This study offers a broader design strategy for the development of transition metal phosphide (TMPs) materials in the oxygen evolution reaction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Blood composition is indicative of health-related traits such as immunity and metabolism. The use of molecular genetics to investigate alterations in these attributes in laying ducks is a novel approach. Our objective was to employ genome - wide association studies (GWAS) and haplotype - sharing analysis to identify genomic regions and potential genes associated with 11 blood components in Shaoxing ducks. Our findings revealed 35 SNPs and 1 SNP associated with low-density lipoprotein cholesterol (LDL) and globulin (GLB), respectively. We identified 36 putative candidate genes for the LDL trait in close proximity to major QTLs and key loci. Based on their biochemical and physiological properties, TRA2A , NPY , ARHGEF26 , DHX36 , and AADAC are the strongest putative candidate genes. Through linkage disequilibrium analysis and haplotype sharing analysis, we identified three haplotypes and one haplotype, respectively, that were significantly linked with LDL and GLB. These haplotypes could be selected as potential candidate haplotypes for molecular breeding of Shaoxing ducks. Additionally, we utilized a bootstrap test to verify the reliability of GWAS with small experimental samples. The test can be accessed at https://github.com/xuwenwu24/Bootstrap-test.

Purpose: Our study aimed to compare the accuracy of the effective atomic number (Z eff ) of five dual-energy CT (DECT) from three vendors and different generations under different scanning parameters., Methods: Z eff accuracy of five DECT scanners with twelve tube voltage configurations was evaluated by using the TomoTherapy cheese phantom. The potential dose dependence of the Z eff was investigated using three radiation dose (5, 15, and 25 mGy), and the robustness of Z eff was simulated for different organs of the body by placing the inserts at different positional depths. Bias and mean absolute percentage error (MAPE) were used to characterize the accuracy of Zeff. Data underwent analysis using one-way ANOVA, followed by the Turky and LSD post hoc tests, simple linear regression, and linear mixed models., Results: All tube voltage configurations had a bias of less than 1. Dual layer detector DECT (dl-DECT) -140 kV has the lowest MAPE (1.79 %±1.93 %). The third generation dual source DECT (ds-DECT) and the second generation rapid switch DECT (rs-DECT) have higher MAPE than their predecessor DECT. The results of the linear mixed model showed that tube voltage configuration (F=16.92, p < 0.001) and insert type (F=53.26, p < 0.001) significantly affect the MAPE. In contrast, radiation dose only has a significant effect on the MAPE of rs-DECT. The inserts position does not affect the final MAPE., Conclusion: When scanning different inserts, Z eff accuracy varies by vendor and DECT generation. Of all the scanners, dl-DECT had the highest Z eff accuracy. Upgrading DECT generation doesn't lead to higher accuracy, or even lower., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Optimizing feed efficiency through the feed conversion ratio (FCR) is paramount for economic viability and sustainability. In this study, we integrated RNA-seq, ATAC-seq, and genome-wide association study (GWAS) data to investigate key functional variants associated with feed efficiency in pigs. Identification of differentially expressed genes in the duodenal and muscle tissues of low- and high-FCR pigs revealed that pathways related to digestion of dietary carbohydrate are responsible for differences in feed efficiency between individuals. Differential open chromatin regions identified by ATAC-seq were linked to genes involved in glycolytic and fatty acid processes. GWAS identified 211 significant single-nucleotide polymorphisms associated with feed efficiency traits, with candidate genes PPP1R14C , TH , and CTSD . Integration of duodenal ATAC-seq data and GWAS data identified six key functional variants, particularly in the 1500985-1509676 region on chromosome 2. In those regions, CTSD was found to be highly expressed in the duodenal tissues of pigs with a high feed conversion ratio, suggesting its role as a potential target gene. Overall, the integration of multi-omics data provided insights into the genetic basis of feed efficiency, offering valuable information for breeding more efficient pig breeds.

This study presents a sensitive and reproducible mass spectrometry method for quantifying skatole in porcine adipose tissue, muscle, and serum samples applicable for abattoirs and laboratories. Leveraging gas chromatography-high-resolution Orbitrap microscopy and microwave-assisted liquefication of the adipose tissue, the method demonstrates robust performance across key parameters. Impressive linearity (R 2 ) values of 0.9999 and 0.9996 for adipose tissue and serum, respectively. Notably, the method exhibits a low Limit of Detection (LoD) of 0.5 ppb for adipose tissue and 0.9 ppb for serum, with corresponding Limits of Quantification (LoQ) at 1.65 ppb and 3.04 ppb, respectively. The method showed significant reproducibility of 5.9% and repeatability (RSD%) of 8.78% for adipose tissue and 4.08% for serum, with recovery rates of 90% and 87%, respectively. This streamlined method offers promising, effective quantification of boar taint compounds, emphasizing its sensitivity and reproducibility., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Electroacupuncture (EA) has been shown to promote functional recovery after cerebral ischemia-reperfusion (I/R) injury. However, the contribution of mitochondrial dynamics to recovery remains unclear. The aim of this study was to investigate whether mitochondrial dynamics are involved in the effects of EA on cerebral I/R injury., Methods: The rats with cerebral I/R injury were established by the middle cerebral artery occlusion/reperfusion. Subsequently, EA was applied to Baihui (GV20) and Dazhui (GV14) acupoints, with 2 Hz/5 Hz in frequency, 1.0 mA in intensity, 20 min each time, once a day for seven consecutive days. The therapeutic outcomes were assessed by modified neurological severity score (mNSS), 2,3,5-Triphenyte-trazolium chloride (TTC) staining, and hematoxylin-eosin (HE) staining. Mitochondrial morphology was observed under transmission electron microscopy. Adenosine triphosphate (ATP) content and ATP synthases (ATPases) activity were evaluated to measure mitochondrial function using ELISA. Finally, mitochondrial dynamics-related molecules, including dynamin-related protein 1 (Drp1), fission 1 (Fis1), mitofusin 1 (Mfn1), mitofusin 2 (Mfn2), and optic atrophy 1 (OPA1), were detected by Western blot and immunofluorescence staining., Results: Cerebral I/R injury induced neurological dysfunction, cerebral infarction and neuronal injury, all of which were ameliorated by EA . And EA improved mitochondrial morphology and function. Moreover, EA altered the balance of mitochondrial dynamics. Specifically, the data showed a significant decrease in the expression of Drp1 and Fis1, leading to the inhibition of mitochondrial fission. Additionally, Mfn1, Mfn2 and Opa1, which are related to mitochondrial fusion, were effectively promoted after EA treatment. However, sham EA did not show any neuroprotective effects in rats with cerebral I/R injury., Conclusions: In summary, our study indicates that the balance of mitochondrial dynamics is crucial for EA therapy to treat cerebral I/R injury., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Purpose: Head injury criterion (HIC) companied by a rotation-based metric was widely believed to be helpful for head injury prediction in road traffic accidents. Recently, the Euro-New Car Assessment Program utilized a newly developed metric called diffuse axonal multi-axis general evaluation (DAMAGE) to explain test device for human occupant restraint (THOR) head injury, which demonstrated excellent ability in capturing concussions and diffuse axonal injuries. However, there is still a lack of comprehensive understanding regarding the effectiveness of using DAMAGE for Hybrid Ⅲ 50th percentile male dummy (H50th) head injury assessment. The objective of this study is to determine whether the DAMAGE could capture the risk of H50th brain injury during small overlap barrier tests., Methods: To achieve this objective, a total of 24 vehicle crash loading curves were collected as input data for the multi-body simulation. Two commercially available mathematical dynamic models, namely H50th and THOR, were utilized to investigate the differences in head injury response. Subsequently, a decision method known as simple additive weighting was employed to establish a comprehensive brain injury metric by incorporating the weighted HIC and either DAMAGE or brain injury criterion. Furthermore, 35 sets of vehicle crash test data were used to analyze these brain injury metrics., Results: The rotational displacement of the THOR head is significantly greater than that of the H50th head. The maximum linear and rotational head accelerations experienced by H50th and THOR models were (544.6 ± 341.7) m/s 2 , (2468.2 ± 1309.4) rad/s 2 and (715.2 ± 332.8) m/s 2 , (3778.7 ± 1660.6) rad/s 2 , respectively. Under the same loading condition during small overlap barrier (SOB) tests, THOR exhibits a higher risk of head injury compared to the H50th model. It was observed that the overall head injury response during the small overlap left test condition is greater than that during the small overlap right test. Additionally, an equation was formulated to establish the necessary relationship between the DAMAGE values of THOR and H50th., Conclusion: If H50th rather than THOR is employed as an evaluation tool in SOB crash tests, newly designed vehicles are more likely to achieve superior performance scores. According to the current injury curve for DAMAGE and brain injury criterion, it is highly recommended that HIC along with DAMAGE was prioritized for brain injury assessment in SOB tests., (Copyright © 2024 Chinese Medical Association. Production and hosting by Elsevier B.V. All rights reserved.)

Purpose: Under-foot impact loadings can cause serious lower limb injuries in many activities, such as automobile collisions and underbody explosions to military vehicles. The present study aims to compare the biomechanical responses of the mainstream vehicle occupant dummies with the human body lower limb model and analyze their robustness and applicability for assessing lower limb injury risk in under-foot impact loading environments., Methods: The Hybrid III model, the test device for human occupant restraint (THOR) model, and a hybrid human body model with the human active lower limb model were adopted for under-foot impact analysis regarding different impact velocities and initial lower limb postures., Results: The results show that the 2 dummy models have larger peak tibial axial force and higher sensitivity to the impact velocities and initial postures than the human lower limb model. In particular, the Hybrid III dummy model presented extremely larger peak tibial axial forces than the human lower limb model. In the case of minimal difference in tibial axial force, Hybrid III's tibial axial force (7.5 KN) is still 312.5% that of human active lower limb's (2.4 KN). Even with closer peak tibial axial force values, the biomechanical response curve shapes of the THOR model show significant differences from the human lower limb model., Conclusion: Based on the present results, the Hybrid III dummy cannot be used to evaluate the lower limb injury risk in under-foot loading environments. In contrast, potential improvement in ankle biofidelity and related soft tissues of the THOR dummy can be implemented in the future for better applicability., (Copyright © 2024. Production and hosting by Elsevier B.V.)

Skeletal muscle satellite cells, the resident stem cells in pig skeletal muscle, undergo proliferation and differentiation to enable muscle tissue repair. The proliferative and differentiative abilities of these cells gradually decrease during in vitro cultivation as the cell passage number increases. Despite extensive research, the precise molecular mechanisms that regulate this process are not fully understood. To bridge this knowledge gap, we conducted transcriptomic analysis of skeletal muscle satellite cells during in vitro cultivation to quantify passage number-dependent changes in the expression of genes associated with proliferation. Additionally, we explored the relationships between gene transcriptional activity and chromatin accessibility using transposase-accessible chromatin sequencing. This revealed the closure of numerous open chromatin regions, which were primarily located in intergenic regions, as the cell passage number increased. Integrated analysis of the transcriptomic and epigenomic data demonstrated a weak correlation between gene transcriptional activity and chromatin openness in expressed genic regions; although some genes (e.g., GNB4 and FGD5 ) showed consistent relationships between gene expression and chromatin openness, a substantial number of differentially expressed genes had no clear association with chromatin openness in expressed genic regions. The p53-p21-RB signaling pathway may play a critical regulatory role in cell proliferation processes. The combined transcriptomic and epigenomic approach taken here provided key insights into changes in gene expression and chromatin openness during in vitro cultivation of skeletal muscle satellite cells. These findings enhance our understanding of the intricate mechanisms underlying the decline in cellular proliferation capacity in cultured cells.

Genetic testing is crucial for precision cancer medicine. However, detecting multiple same-site insertions or deletions (indels) is challenging. Here, we introduce CoHIT (Cas12a-based One-for-all High-speed Isothermal Test), a one-pot CRISPR-based assay for indel detection. Leveraging an engineered AsCas12a protein variant with high mismatch tolerance and broad PAM scope, CoHIT can use a single crRNA to detect multiple NPM1 gene c.863&#95;864 4-bp insertions in acute myeloid leukemia (AML). After optimizing multiple parameters, CoHIT achieves a detection limit of 0.01% and rapid results within 30 minutes, without wild-type cross-reactivity. It successfully identifies NPM1 mutations in 30 out of 108 AML patients and demonstrates potential in monitoring minimal residual disease (MRD) through continuous sample analysis from three patients. The CoHIT method is also competent for detecting indels of KIT, BRAF, and EGFR genes. Integration with lateral flow test strips and microfluidic chips highlights CoHIT's adaptability and multiplexing capability, promising significant advancements in clinical cancer diagnostics., (© 2024. The Author(s).)

Biogenic selenium nanoparticles (SeNPs) are the most favorable Se form for nutritional supplementation due to their high stability, low toxicity, and high activity. However, the interaction between the surface-binding proteins and their stable biogenic SeNPs, as well as their impact on the stability and bioavailability of SeNPs, remains to be understood. In vitro stabilization experiments revealed an amino acid segment (F(235-386)) in Rahnella aquatilis ' flagellin FliC, with surfactant-like properties, stabilizing SeNPs under harsh conditions. FliC and F(235-386) were employed as stabilizers to synthesize SeNPs (FliC@SeNPs and F(235-386)@SeNPs), and surface chemistry analysis revealed coordination reactions between the proteins and Se atoms on the surface of SeNPs. Both FliC and F(235-386) enhanced SeNPs uptake in wheat seedlings but reduced it in bacteria and yeast. This study highlights FliC's core function in stabilizing SeNPs and enhancing their bioavailability, paving the way for agricultural and nutritional applications.

Aims: Some studies have indicated that the alterations in cellular morphology induced by selenite [Se(Ⅳ)] may be attributed to its inhibitory effects on cell division. However, whether the genes associated with cell division are implicated in Se(Ⅳ) metabolism remains unclear., Methods and Results: The ftsK gene in Rahnella aquatilis HX2 was mutated with an in-frame deletion strategy. The ftsK mutation strongly reduced the tolerance to selenite [Se(Ⅳ)] and the production of red elemental selenium [Se(0)] in R. aquatilis HX2, and this effect could not be attributed solely to the inhibition of cell growth. Deleting the ftsK gene also resulted in a significant decrease in bacterial growth of R. aquatilis HX2 during both exponential and stationary phases. The deletion of ftsK inhibited cell division, resulting in the development of elongated filamentous cells. Furthermore, the loss-of-function of FtsK significantly impacted the expression of seven genes linked to cell division and Se(Ⅳ) metabolism by at least 2-fold, as unveiled by real-time quantitative PCR (RT-qPCR) under Se(Ⅳ) treatment., Conclusions: These findings suggest that FtsK is associated with Se(Ⅳ) tolerance and Se(0) generation and is a key player in coordinating bacterial growth and cell morphology in R. aquatilis HX2., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)

In this study, Cu-Cu 2 O/PtPd nanocomposites were synthesized and characterized for their peroxidase-like enzyme activity. X-ray diffraction and energy dispersive X-ray spectroscopy analyses confirmed the successful synthesis of the nanocomposites, which exhibited a flower-like morphology and a more uniform dispersion than Cu-Cu 2 O. The catalytic activity of Cu-Cu 2 O/PtPd was evaluated using the chromogenic substrate 3,3',5,5'-tetramethylbenzidine (TMB), finding that Cu-Cu 2 O/PtPd outperformed Cu-Cu 2 O. The optimal temperature and pH for the catalytic activity of Cu-Cu 2 O/PtPd were determined to be 40 °C and pH 4.0, respectively. A kinetic analysis revealed that Cu-Cu 2 O/PtPd followed Michaelis-Menten kinetics and exhibited a higher affinity toward TMB than the horseradish peroxidase enzyme. The catalytic mechanism of Cu-Cu 2 O/PtPd involved the generation of hydroxyl radicals, which facilitated the oxidation of TMB. Furthermore, the Cu-Cu 2 O/PtPd nanocomposite was successfully applied for the colorimetric detection of glucose, demonstrating a linear range of 8-90 μM, a detection limit of 2.389 μM, and high selectivity for glucose over other sugars., Competing Interests: Declaration of competing interest All authors disclosed no relevant relationships., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To review the effectiveness of different physical therapies for acute and sub-acute low back pain supported by evidence, and create clinical recommendations and expert consensus for physiotherapists on clinical prescriptions., Data Sources: A systematic search was conducted in PubMed and the Cochrane Library for studies published within the previous 15 years., Review Methods: Systematic review and meta-analysis, randomized controlled trials assessing patients with acute and sub-acute low back pain were included. Two reviewers independently screened relevant studies using the same inclusion criteria. The Physiotherapy Evidence Database and the Assessment of Multiple Systematic Reviews tool were used to grade the quality assessment of randomized controlled trials and systematic reviews, respectively. The final recommendation grades were based on the consensus discussion results of the Delphi of 22 international experts., Results: Twenty-one systematic reviews and 21 randomized controlled trials were included. Spinal manipulative therapy and low-level laser therapy are recommended for acute low back pain. Core stability exercise/motor control, spinal manipulative therapy, and massage can be used to treat sub-acute low back pain., Conclusions: The consensus statements provided medical staff with appliable recommendations of physical therapy for acute and sub-acute low back pain. This consensus statement will require regular updates after 5-10 years., Competing Interests: Declaration of conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: The absence of predictive models for early latent tuberculosis infection (LTBI) progression persists. This study aimed to create a screening model to identify high-risk LTBI patients prome to active tuberculosis (ATB) reactivation., Methodology: Patients with confirmed ATB were enrolled alongside LTBI individuals as a reference, with relevant clinical data gathered. LASSO regression cross-validation reduced data dimensionality. A nomogram was developed using multiple logistic regression, internally validated with Bootstrap resampling. Evaluation included C-index, receiver operating characteristic (ROC) curve, and calibration curves, with clinical utility assessed through decision curve analysis., Results: The final nomogram incorporated serum albumin (OR = 1.337, p = 0.046), CD4+ (OR = 1.010, p = 0.004), and CD64 index (OR = 0.009, p = 0.020). The model achieved a C-index of 0.964, an area under the ROC curve of 0.962 (95% CI: 0.926-0.997), sensitivity of 0.971, and specificity of 0.910. Internal validation showed a mean absolute error of 0.013 and 86.4% identification accuracy. The decision curve indicated substantial net benefit at a risk threshold exceeding 10% (1: 9)., Conclusions: This study established a biologically-rooted nomogram for high-risk LTBI patients prone to ATB reactivation, offering strong predictability, concordance, and clinical value. It serves as a personalized risk assessment tool, accurately identifying patients necessitating priority prophylactic treatment, complementing existing host risk factors effectively., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 Kui Li, Siyi Liu, Yingli He, Renyu Ran.)

Herein, ionomer-free amorphous iridium oxide (IrO x ) thin electrodes are first developed as highly active anodes for proton exchange membrane electrolyzer cells (PEMECs) via low-cost, environmentally friendly, and easily scalable electrodeposition at room temperature. Combined with a Nafion 117 membrane, the IrO x -integrated electrode with an ultralow loading of 0.075 mg cm -2 delivers a high cell efficiency of about 90%, achieving more than 96% catalyst savings and 42-fold higher catalyst utilization compared to commercial catalyst-coated membrane (2 mg cm -2 ). Additionally, the IrO x electrode demonstrates superior performance, higher catalyst utilization and significantly simplified fabrication with easy scalability compared with the most previously reported anodes. Notably, the remarkable performance could be mainly due to the amorphous phase property, sufficient Ir 3+ content, and rich surface hydroxide groups in catalysts. Overall, due to the high activity, high cell efficiency, an economical, greatly simplified and easily scalable fabrication process, and ultrahigh material utilization, the IrO x electrode shows great potential to be applied in industry and accelerates the commercialization of PEMECs and renewable energy evolution., (© 2024. The Author(s).)

The combination of radiotherapy (RT) and immunotherapy shows promise in improving the clinical treatment of solid tumors; however, it faces challenges of low response rates and systemic toxicity. Herein, an implantable alginate/collagen hydrogel encapsulating C-C motif ligand 21 (CCL21)-expressing dendritic cells (CCL21-DCs@gel) was developed to potentiate the systemic antitumor effects of RT. The hydrogel functioned as a suitable reservoir for in vivo culture and proliferation of CCL21-DCs, thereby enabling sustained CCL21 release. The local CCL21 gradient induced by CCL21-DCs@gel significantly enhanced the efficacy of RT in suppressing primary tumor growth and inhibiting distant metastasis across several mouse models. Furthermore, the combination of RT with CCL21-DCs@gel provided complete prophylactic protection to mice. Mechanistic investigations revealed that CCL21-DCs@gel potentiated RT by promoting tumor lymphangiogenesis and attracting immune cell infiltration into the tumor. Collectively, these results suggest that CCL21-DCs@gel is a promising adjunct to RT for effectively eradicating tumors and preventing tumor recurrence.

Biofilms attached to submerged macrophytes play an important role in improving the water quality of the water environment supplemented with reclaimed water. In order to explore the effects of reclaimed water quality and submerged macrophyte species on the characteristics of an epiphytic bacterial community, different types of submerged macrophytes were selected as research objects in this study. 16S rRNA high-throughput sequencing technology was used on the epiphytic bacteria and the surrounding environmental samples to analyze the bacterial community structure and functional genes. The results showed that approximately 20%-35% of the nitrogen and phosphorus nutrients were absorbed and utilized in the water environment supplemented with reclaimed water. However, the COD, turbidity, and chroma of the downstream water were significantly increased. The bacterial community of the biofilms attached to submerged macrophytes was significantly different from that in the surrounding environment (soil, sediment, and water body) and in the activated sludge that was treated by reclaimed water. In terms of bacterial community diversity, the richness and diversity were significantly lower than those of soil and sediment but higher than those of plankton bacteria in water. In terms of bacterial community composition, dominant genera and corresponding abundances were also different from those of other samples. The main dominant bacterial genera were Sphingomonas , Aeromonas , Pseudomonas, and Acinetobacter , accounting for 7%-40%, respectively. Both macrophyte species and the quality of reclaimed water (BOD 5 , TN, NH 4 + -N, and TP) could affect the bacterial community. However, the effect of water quality of the bacterial community was greater than that of macrophytes species. Additionally, the quality of reclaimed water also affected the abundance of functional genes in the bacterial community, and the relative abundance of nitrogen and phosphorus cycling functional genes was higher in areas with higher nitrogen and phosphorus concentrations.

Background: Structural variations (SVs) have significant impacts on complex phenotypes by rearranging large amounts of DNA sequence., Results: We present a comprehensive SV catalog based on the whole-genome sequence of 1060 pigs (Sus scrofa) representing 101 breeds, covering 9.6% of the pig genome. This catalog includes 42,487 deletions, 37,913 mobile element insertions, 3308 duplications, 1664 inversions, and 45,184 break ends. Estimates of breed ancestry and hybridization using genotyped SVs align well with those from single nucleotide polymorphisms. Geographically stratified deletions are observed, along with known duplications of the KIT gene, responsible for white coat color in European pigs. Additionally, we identify a recent SINE element insertion in MYO5A transcripts of European pigs, potentially influencing alternative splicing patterns and coat color alterations. Furthermore, a Yorkshire-specific copy number gain within ABCG2 is found, impacting chromatin interactions and gene expression across multiple tissues over a stretch of genomic region of ~200 kb. Preliminary investigations into SV's impact on gene expression and traits using the Pig Genotype-Tissue Expression (PigGTEx) data reveal SV associations with regulatory variants and gene-trait pairs. For instance, a 51-bp deletion is linked to the lead eQTL of the lipid metabolism regulating gene FADS3, whose expression in embryo may affect loin muscle area, as revealed by our transcriptome-wide association studies., Conclusions: This SV catalog serves as a valuable resource for studying diversity, evolutionary history, and functional shaping of the pig genome by processes like domestication, trait-based breeding, and adaptive evolution., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Biogenic selenium nanoparticles (SeNPs) show numerous advantages including their high stability, low toxicity, and high bioactivity. While metabolism of SeNPs remains not well studied and need more investigation to reveal the process., Purpose: The objective of the study was to investigate the relationship between nitrate reductase and selenite reduction in Rahnella aquatilis HX2, characterize the properties of HX2 produced SeNPs, and explore their potential applications, particularly their anticancer activity., Procedures: Selenium species were measured by high-performance liquid chromatography coupled to inductively coupled plasma - Mass spectrometry (HPLC-ICP-MS). Transcription level of nitrate reductase was determined by Real-time quantitative PCR. Morphology, particle size, crystal structure and surface chemistry of SeNPs were determined by electron microscopy, dynamic light scattering method, Raman scattering, X-ray photoelectron spectroscopy, respectively. Anti cancer cell activity was measured by CCK-8 assay., Main Findings: SeNP production in R. aquatilis HX2 was correlated with the cell growth. The products of selenite reduction in HX2 detected by HPLC-ICP-MS included SeNPs, selenocysteine (SeCys), Se-Methylselenocysteine (MeSeCys), and 7 unknown compounds. Nitrate addition experiments suggested the involvement of nitrate reductase in selenite reduction in HX2. Both the cellular membrane and cytoplasm of HX2 exhibited selenite-reducing ability, indicating that membrane-associated nitrate reductase was not the sole selenite reductase in HX2. Characterization of the biogenic SeNPs revealed a spherical morphology and amorphous structure of them. Surface chemistry analysis implicated the binding of extracellular polymeric substances to the biogenic SeNPs, and the presence of Se 0 , Se 2- , and electron-rich Se atoms on the surface of SeNPs. Finally, the IC50 values of the biogenic SeNPs were 36.49 μM for HepG2 and 3.70 μM for HeLa cells., Conclusions: The study first revealed that the nitrate reductase is involving in selenite reduction in R. aquatilis HX2. The biogenic SeNPs coordinated with organic substances in the surface. And SeNPs produced by R. aquatilis HX2 showed excellent anticancer activities on HepG2 and HeLa cells., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Conflict of Interest All authors declare that there is no conflict of interest in this work., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Immune checkpoint blockade (ICB) has achieved groundbreaking results in clinical cancer therapy; however, only a subset of patients experience durable benefits. The aim of this study was to explore strategies for predicting tumor responses to optimize the intervention approach using ICB therapy. Methods: We used a bilateral mouse model for proteomics analysis to identify new imaging biomarkers for tumor responses to ICB therapy. A PET radiotracer was synthesized by radiolabeling the identified biomarker-targeting antibody with 124 I. The radiotracer was then tested for PET prediction of tumor responses to ICB therapy. Results: We identified galectin-1 (Gal-1), a member of the carbohydrate-binding lectin family, as a potential negative biomarker for ICB efficacy. We established that Gal-1 inhibition promotes a sensitive immune phenotype within the tumor microenvironment (TME) for ICB therapy. To assess the pre-ICB treatment status of the TME, a Gal-1-targeted PET radiotracer, 124 I-αGal-1, was developed. PET imaging with 124 I-αGal-1 showed the pretreatment immunosuppressive status of the TME before the initiation of therapy, thus enabling the prediction of ICB resistance in advance. Moreover, the use of hydrogel scaffolds loaded with a Gal-1 inhibitor, thiodigalactoside, demonstrated that a single dose of thiodigalactoside-hydrogel significantly potentiated ICB and adoptive cell transfer immunotherapies by remodeling the immunosuppressive TME. Conclusion: Our study underscores the potential of Gal-1-targeted PET imaging as a valuable strategy for early-stage monitoring of tumor responses to ICB therapy. Additionally, Gal-1 inhibition effectively counteracts the immunosuppressive TME, resulting in enhanced immunotherapy efficacy., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: Cerebral edema (CE) is the main secondary injury following traumatic brain injury (TBI) caused by road traffic accidents (RTAs). It is challenging to be predicted timely. In this study, we aimed to develop a prediction model for CE by identifying its risk factors and comparing the timing of edema occurrence in TBI patients with varying levels of injuries., Methods: This case-control study included 218 patients with TBI caused by RTAs. The cohort was divided into CE and non-CE groups, according to CT results within 7 days. Demographic data, imaging data, and clinical data were collected and analyzed. Quantitative variables that follow normal distribution were presented as mean ± standard deviation, those that do not follow normal distribution were presented as median (Q 1 , Q 3 ). Categorical variables were expressed as percentages. The Chi-square test and logistic regression analysis were used to identify risk factors for CE. Logistic curve fitting was performed to predict the time to secondary CE in TBI patients with different levels of injuries. The efficacy of the model was evaluated using the receiver operator characteristic curve., Results: According to the study, almost half (47.3%) of the patients were found to have CE. The risk factors associated with CE were bilateral frontal lobe contusion, unilateral frontal lobe contusion, cerebral contusion, subarachnoid hemorrhage, and abbreviated injury scale (AIS). The odds ratio values for these factors were 7.27 (95% confidence interval (CI): 2.08 - 25.42, p = 0.002), 2.85 (95% CI: 1.11 - 7.31, p = 0.030), 2.62 (95% CI: 1.12 - 6.13, p = 0.027), 2.44 (95% CI: 1.25 - 4.76, p = 0.009), and 1.5 (95% CI: 1.10 - 2.04, p = 0.009), respectively. We also observed that patients with mild/moderate TBI (AIS ≤ 3) had a 50% probability of developing CE 19.7 h after injury (χ 2  = 13.82, adjusted R 2  = 0.51), while patients with severe TBI (AIS > 3) developed CE after 12.5 h (χ 2  = 18.48, adjusted R 2  = 0.54). Finally, we conducted a receiver operator characteristic curve analysis of CE time, which showed an area under the curve of 0.744 and 0.672 for severe and mild/moderate TBI, respectively., Conclusion: Our study found that the onset of CE in individuals with TBI resulting from RTAs was correlated with the severity of the injury. Specifically, those with more severe injuries experienced an earlier onset of CE. These findings suggest that there is a critical time window for clinical intervention in cases of CE secondary to TBI., (Copyright © 2024 Chinese Medical Association. Production and hosting by Elsevier B.V. All rights reserved.)

Acidic residues (Asp and Glu) have a high prevalence on protein surfaces, but cross-linking reactions targeting these residues are limited. Existing methods either require high-concentration coupling reagents or have low structural compatibility. Here a previously reported "plant-and-cast" strategy is extended to develop heterobifunctional cross-linkers. These cross-linkers first react rapidly with Lys sidechains and then react with Asp and Glu sidechains, in a proximity-enhanced fashion. The cross-linking reaction proceeds at neutral pH and room temperature without coupling reagents. The efficiency and robustness of cross-linking using model proteins, ranging from small monomeric proteins to large protein complexes are demonstrated. Importantly, it is shown that this type of cross-linkers are efficient at identifying protein-protein interactions involving acidic domains. The Cross-linking mass spectrometry (XL-MS) study with p53 identified 87 putative binders of the C-terminal domain of p53. Among them, SARNP, ZRAB2, and WBP11 are shown to regulate the expression and alternative splicing of p53 target genes. Thus, these carboxylate-reactive cross-linkers will further expand the power of XL-MS in the analysis of protein structures and protein-protein interactions., (© 2023 Wiley‐VCH GmbH.)

Tripartite-motif protein-56 (TRIM56) positively regulates the induction of type I interferon response via the TLR3 pathway by enhancing IRF3 activation and depends on its C-terminal residues 621-750 for interacting with the adaptor TRIF. However, the precise underlying mechanism and detailed TRIM56 determinants remain unclear. Herein, we show ectopic expression of murine TRIM56 also enhances TLR3-dependent interferon-β promoter activation, suggesting functional conservation. We found that endogenous TRIM56 and TRIF formed a complex early (0.5-2 h) after poly-I:C stimulation and that TRIM56 overexpression also promoted activation of NF-κB by poly-I:C but not that by TNF-α or IL-1β, consistent with a specific effect on TRIF prior to the bifurcation of NF-κB and IRF3. Using transient transfection and Tet-regulated cell lines expressing various TRIM56 mutants, we demonstrated the Coiled-coil domain and a segment spanning residues ∼434-610, but not the B-box or residues 355-433, were required for TRIM56 augmentation of TLR3 signaling. Moreover, alanine substitution at each putative phosphorylation site, Ser 471 , Ser 475 , and Ser 710 , abrogated TRIM56 function. Concordantly, mutants bearing Ser 471 Ala, Ser 475 Ala, or Ser 710 Ala, or lacking the Coiled-coil domain, all lost the capacity to enhance poly-I:C-induced establishment of an antiviral state. Furthermore, the Ser 710 Ala mutation disrupted the TRIM56-TRIF association. Using phospho-specific antibodies, we detected biphasic phosphorylation of TRIM56 at Ser 471 and Ser 475 following TLR3 stimulation, with the early phase occurring at ∼0.5 to 1 h, prior to IRF3 phosphorylation. Together, these data reveal novel molecular details critical for the TRIM56 augmentation of TLR3-dependent antiviral response and highlight important roles for TRIM56 scaffolding and phosphorylation., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Enhancer RNAs (eRNAs) play a crucial role in transcriptional regulation. While significant progress has been made in understanding epigenetic regulation mediated by eRNAs, research on the construction of eRNA-mediated gene regulatory networks (eGRN) and the identification of critical network components that influence complex traits is lacking., Results: Here, employing the pig as a model, we conducted a comprehensive study using H3K27ac histone ChIP-seq and RNA-seq data to construct eRNA expression profiles from multiple tissues of two distinct pig breeds, namely Enshi Black (ES) and Duroc. In addition to revealing the regulatory landscape of eRNAs at the tissue level, we developed an innovative network construction and refinement method by integrating RNA-seq, ChIP-seq, genome-wide association study (GWAS) signals and enhancer-modulating effects of single nucleotide polymorphisms (SNPs) measured by self-transcribing active regulatory region sequencing (STARR-seq) experiments. Using this approach, we unraveled eGRN that significantly influence the growth and development of muscle and fat tissues, and identified several novel genes that affect adipocyte differentiation in a cell line model., Conclusions: Our work not only provides novel insights into the genetic basis of economic pig traits, but also offers a generalizable approach to elucidate the eRNA-mediated transcriptional regulation underlying a wide spectrum of complex traits for diverse organisms., (© 2024. The Author(s).)

The performance of two thermoluminescent dosimetry systems (RGD-3D and RE2000) manufactured in China and Finland was compared. Both of these dosimetry systems demonstrated satisfactory results as their performance met the requirements of the standard. The two dosimetry systems showed similar performance in the energy response. The RGD-3D dosimetry system performed better in nonlinear response, minimum detectable level and blind sample tests, whereas the RE2000 dosimetry system showed better stability., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Aims: Isoniazid (INH) has been used as a first-line drug to treat tuberculosis (TB) for more than 50 years. However, large interindividual variability was found in its pharmacokinetics, and effects of nonadherence to INH treatment and corresponding remedy regime remain unclear. This study aimed to develop a population pharmacokinetic (PPK) model of INH in Chinese patients with TB to provide model-informed precision dosing and explore appropriate remedial dosing regimens for nonadherent patients., Methods: In total, 1012 INH observations from 736 TB patients were included. A nonlinear mixed-effects modelling was used to analyse the PPK of INH. Using Monte Carlo simulations to determine optimal dosage regimens and design remedial dosing regimens., Results: A 2-compartmental model, including first-order absorption and elimination with allometric scaling, was found to best describe the PK characteristics of INH. A mixture model was used to characterize dual rates of INH elimination. Estimates of apparent clearance in fast and slow eliminators were 28.0 and 11.2 L/h, respectively. The proportion of fast eliminators in the population was estimated to be 40.5%. Monte Carlo simulations determined optimal dosage regimens for slow and fast eliminators with different body weight. For remedial dosing regimens, the missed dose should be taken as soon as possible when the delay does not exceed 12 h, and an additional dose is not needed. delay for an INH dose exceeds 12 h, the patient only needs to take the next single dose normally., Conclusion: PPK modelling and simulation provide valid evidence on the precision dosing and remedial dosing regimen of INH., (© 2024 British Pharmacological Society.)

Background: The fetal neurodevelopmental microstructural alterations of intrauterine exposure to preeclampsia (PE) or gestational hypertension (GH) remain unknown., Purpose: To evaluate the differences in diffusion-weighted imaging (DWI) of the fetal brain between normotensive pregnancies and PE/GH pregnancies, with a focus on PE/GH pregnancies with fetal growth restriction (FGR)., Study Type: Retrospective matched case-control study., Population: 40 singleton pregnancies with PE/GH complicated by FGR, and 3 paired control groups (PE/GH without FGR, normotensive FGR, normotensive pregnancies) (28-38 gestational weeks)., Field Strength/sequence: DWI with single-shot echo-planar imaging at 1.5 Tesla., Assessment: The apparent diffusion coefficient (ADC) values were calculated in the centrum semi-ovale (CSO), parietal white matter (PWM), frontal white matter (FWM), occipital white matter (OWM), temporal white matter (TWM), basal ganglia, thalamus (THAL), pons, and cerebellar hemisphere., Statistical Tests: Student t test or Wilcoxon matched test was used to reveal the difference of ADC values among the investigated brain regions. A correlation between gestational age (GA) and ADC values was determined by linear regression analysis., Results: Compared with fetuses in PE/GH without FGR and those with normotensive pregnancies, fetuses in the PE/GH with FGR group had significantly lower average ADC measurements of supratentorial regions (1.65 ± 0.09 vs. 1.71 ± 0.10 10 -3  mm 2 /sec; vs. 1.73 ± 0.11 10 -3  mm 2 /sec, respectively). Regions of significantly decreased ADC values in the fetal brain included CSO, FWM, PWM, OWM, TWM and THAL in cases of PE/GH with FGR. ADC values from supratentorial regions in PE/GH pregnancies were not significantly correlated with GA (P = 0.12, 0.26); however, this trend was statistically significant in the normotensive groups., Data Conclusion: ADC values may indicate fetal brain developmental alterations in PE/GH with FGR fetuses but more microscopic and morphological studies are necessary to provide additional evidence to offer a different interpretation of this trend in fetal brain., Level of Evidence: 4 TECHNICAL EFFICACY STAGE: 3., (© 2023 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Two Gram-stain-negative bacterial strains, R39 T and R73 T , were isolated from the rhizosphere soil of the selenium hyperaccumulator Cardamine hupingshanesis in China. Strain R39 T transformed selenite into elemental and volatile selenium, whereas strain R73 T transformed both selenate and selenite into elemental selenium. Phylogenetic and phylogenomic analyses indicated that strain R39 T belonged to the genus Achromobacter , while strain R73 T belonged to the genus Buttiauxella . Strain R39 T (genome size, 6.68 Mb; G+C content, 61.6 mol%) showed the closest relationship to Achromobacter marplatensis LMG 26219 T and Achromobacter kerstersii LMG 3441 T , with average nucleotide identity (ANI) values of 83.6 and 83.4 %, respectively. Strain R73 T (genome size, 5.22 Mb; G+C content, 50.3 mol%) was most closely related to Buttiauxella ferragutiae ATCC 51602 T with an ANI value of 86.4 %. Furthermore, strain A111 from the GenBank database was found to cluster with strain R73 T within the genus Buttiauxella through phylogenomic analyses. The ANI and digital DNA-DNA hybridization values between strains R73 T and A111 were 97.5 and 80.0% respectively, indicating that they belong to the same species. Phenotypic characteristics also differentiated strain R39 T and strain R73 T from their closely related species. Based on the polyphasic analyses, strain R39 T and strain R73 T represent novel species of the genera Achromobacter and Buttiauxella , respectively, for which the names Achromobacter seleniivolatilans sp. nov. (type strain R39 T =GDMCC 1.3843 T =JCM 36009 T ) and Buttiauxella selenatireducens sp. nov. (type strain R73 T =GDMCC 1.3636 T =JCM 35850 T ) are proposed.

Tripartite motif 21 (TRIM21) is a cytosolic Fc receptor that targets antibody-bound, internalized pathogens for destruction. Apart from this intrinsic defense role, TRIM21 is implicated in autoimmune diseases, inflammation, and autophagy. Whether TRIM21 participates in host interactions with influenza A virus (IAV), however, is unknown. By computational modeling of body weight and lung transcriptome data from the BXD parents (C57BL/6 J (B6) and DBA/2 J (D2)) and 41 BXD mouse strains challenged by IAV, we reveal that a Trim21-associated gene network modulates the early host responses to IAV infection. Trim21 transcripts were significantly upregulated in infected mice of both B6 and D2 backgrounds. Its expression was significantly higher in infected D2 than in infected B6 early after infection and significantly correlated with body weight loss. We identified significant trans-eQTL on chromosome 14 that regulates Trim21 expression. Nr1d2 and Il3ra were among the strongest candidate genes. Pathway analysis found Trim21 to be involved in inflammation and immunity related pathways, such as inflammation signaling pathways (TNF, IL-17, and NF-κB), viral detection signaling pathways (NOD-like and RIG-I-like), influenza, and other respiratory viral infections. Knockdown of TRIM21 in human lung epithelial A549 cells significantly augmented IAV-induced expression of IFNB1, IFNL1, CCL5, CXCL10, and IFN-stimulated genes including DDX58 and IFIH1, among others. Our data suggest that a TRIM21-associated gene network is involved in several aspects of inflammation and viral detection mechanisms during IAV infection. We identify and validate TRIM21 as a critical regulator of innate immune responses to IAV in human lung epithelial cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Objective: The pathogenesis of diarrhea-predominant irritable bowel syndrome (IBS-D) is related to damage to the intestinal mucosal barrier function. Based on the Mast cell (MC)/Tryptase/Protease-activated receptor-2 (PAR-2)/Myosin light chain kinase (MLCK) pathway, this study explored the effect of electroacupuncture (EA) on IBS-D rats and its possible mechanism of protecting the intestinal mucosal barrier., Methods: The IBS-D rat model was established by mother-offspring separation, acetic acid enema, and chronic restraint stress. The efficacy of EA on IBS-D rats was evaluated by observing the rate of loose stool (LSP) and the minimum volume threshold of abdominal withdrawal reflex (AWR) in rats. Mast cells and the ultrastructure of intestinal mucosa were observed by H&E staining, toluidine blue staining, and transmission electron microscopy. The expression levels of Tryptase, PAR-2, MLCK, zonula occludens-1 (ZO-1), and Occludin in rats were detected by ELISA, qRT-PCR, and western blot., Results: After 7 days of intervention, compared to the IBS-D group, the loose stool rates of rats in IBS-D + EA group and IBS-D + ketotifen group were decreased ( P < 0.01), the minimum volume thresholds of AWR were improved ( P < 0.01), the inflammation of colon tissue decreased, the number of MCs were decreased ( P < 0.01), the expression of Tryptase, PAR-2, and MLCK were lowered ( P < 0.01, P < 0.05), and the expression of ZO-1 and Occludin were enhanced ( P < 0.01, P < 0.05). Compared to the EA group, there was no significant difference in each index between the ketotifen groups ( P > 0.05)., Conclusion: EA has a good therapeutic effect on IBS-D rats. Regulating the MCs/Tryptase/PAR-2/MLCK pathway may be a mechanism to protect the intestinal mucosal barrier., Competing Interests: None., (AJTR Copyright © 2024.)

Microorganisms play a critical role in the biogeochemical cycling of selenium, often reducing selenite/selenate to elemental selenium nanoparticles (SeNPs). These SeNPs typically exist in an amorphous structure but can transform into a trigonal allotrope. However, the crystal structural transition process and its impact on selenium bioavailability have not been well studied. To shed light on this, we prepared chemosynthetic and biogenic SeNPs and investigated the stability of their crystal structure. We found that biogenic SeNPs exhibited a highly stable amorphous structure in various conditions, such as lyophilization, washing, and laser irradiation, whereas chemosynthetic SeNPs transformed into a trigonal structure in the same conditions. Additionally, a core-shell structure was observed in biogenic SeNPs after electron beam irradiation. Further analysis revealed that biogenic SeNPs showed a coordination reaction between Se atoms and surface binding biomacromolecules, indicating that the outer layer of Se-biomacromolecules complex prevented the SeNPs from crystallizing. We also investigated the effects of SeNPs crystal structures on the bioavailability in bacteria, yeast, and plants, finding that the amorphous structure of SeNPs determined Se bioavailability., Competing Interests: Declaration of competing interest No conflict of interest exists in the submission of this manuscript, and manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. All the authors listed (Kui Li, Jing Li, Sasa Zhang, Jingrui Zhang, Qiaolin Xu, Zhongnan Xu, and Yanbin Guo) have approved the manuscript that is enclosed.., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The impact of carbonate alkalinity in saline-alkaline water on aquatic organisms, particularly Penaeus vannamei, a significant species in aquaculture, remains a critical area of study. To elucidate the acute response mechanisms of P. vannamei to elevated carbonate alkalinity environments, we utilized 16S rRNA gene and transcriptome sequencing technologies to analyze intestinal bacteria and gene expressions within various tissues. Our investigation revealed notable changes in specific intestinal bacterial OTUs, whose abundances varied preceding the overall bacterial community, indicating the sensitivity to carbonate alkalinity exposure. These shifts are accompanied by a simplification in bacterial networks and alterations in pathogenic OTUs, notably Aeromonas OTU. Concurrently, gene expression variations were observed across the hepatopancreas, gills, muscles, and intestines, with decreasing numbers of DEGs in the mentioned order. Annotation of these DEGs revealed enrichments in pathways related to transport, catabolism, immune responses, circulatory functions, and lipid metabolism. Notably, correlations between specific intestinal bacterial OTUs and gene expression shifts were identified across these tissues. Several OTUs, attributed to Rhizobiales, Saccharimonadales, Acidovora, and Aeromona, exhibited a correlation with DEGs in all four tissues, primarily associated with amino acid metabolism, signal transduction, and transport and catabolism pathways. Our study provides comprehensive insights into the dynamic responses of P. vannamei to elevated carbonate alkalinity stress. These findings contribute crucial knowledge for effective P. vannamei cultivation in saline-alkaline water, advancing our understanding in this field., (Copyright © 2024 Elsevier Ltd. All rights reserved.)