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Abstract Diabetic nephropathy (DN) is a prototypical chronic energy metabolism imbalance disease. The AMPK/Sirt1/PGC-1α signaling pathway plays a pivotal role in regulating energy metabolism throughout the body. Gut microbiota ferment indigestible carbohydrates to produce a variety of metabolites, particularly short-chain fatty acids (SCFAs), which exert positive effects on energy metabolism. However, the potential for SCFAs to ameliorate DN-associated renal injury via the AMPK/Sirt1/PGC-1α pathway remains a matter of debate. In this study, we investigated the effects of sodium butyrate (NaB), a SCFA, on energy metabolism in mice with spontaneous DN at two different doses. Body weight, blood glucose and lipid levels, urinary protein excretion, liver and kidney function, interleukin-6 (IL-6) levels, and the expressions of AMPK, phosphorylated AMPK (p-AMPK), mitofusin 2 (MFN2), optic atrophy 1 (OPA1), and glucagon-like peptide-1 receptor (GLP-1R) were monitored in mice. Additionally, butyrate levels, gut microbiota composition, and diversity in colonic stool were also assessed. Our findings demonstrate that exogenous NaB supplementation can improve hyperglycemia and albuminuria, reduce renal tissue inflammation, inhibit extracellular matrix accumulation and glomerular hypertrophy, and could alter the gut microbiota composition in DN. Furthermore, NaB was found to upregulate the expressions of MFN2, OPA1, p-AMPK, and GLP-1R in DN renal tissue. These results suggest that NaB could improve the composition of gut microbiota in DN, activate the AMPK/Sirt1/PGC-1α signaling pathway, and enhance mitochondrial function to regulate energy metabolism throughout the body. Collectively, our findings indicate that NaB may be a novel therapeutic agent for the treatment of DN.

Abstract UFMylation is a highly conserved ubiquitin-like post-translational modification that catalyzes the covalent linkage of UFM1 to its target proteins. This modification plays a critical role in the maintenance of endoplasmic reticulum proteostasis, DNA damage response, autophagy, and transcriptional regulation. Mutations in UFM1, as well as in its specific E1 enzyme UBA5 and E2 enzyme UFC1, have been genetically linked to microcephaly. Our previous research unveiled the important role of UFMylation in regulating mitosis. However, the underlying mechanisms have remained unclear due to the limited identification of substrates. In this study, we identified Eg5, a motor protein crucial for mitotic spindle assembly and maintenance, as a novel substrate for UFMylation and identified Lys564 as the crucial UFMylation site. UFMylation did not alter its transcriptional level, phosphorylation level, or protein stability, but affected the mono-ubiquitination of Eg5. During mitosis, Eg5 and UFM1 co-localize at the centrosome and spindle apparatus, and defective UFMylation leads to diminished spindle localization of Eg5. Notably, the UFMylation-defective Eg5 mutant (K564R) exhibited shorter spindles, metaphase arrest, spindle checkpoint activation, and a failure of cell division in HeLa cells. Overall, Eg5 UFMylation is essential for proper spindle organization, mitotic progression, and cell proliferation.

Abstract Melanoma is one of the most prevalent skin cancers, with high metastatic rates and poor prognosis. Understanding its molecular pathogenesis is crucial for improving its diagnosis and treatment. Integrated analysis of multi-omics data from 207 treatment-naïve melanomas (primary-cutaneous-melanomas (CM, n = 28), primary-acral-melanomas (AM, n = 81), primary-mucosal-melanomas (MM, n = 28), metastatic-melanomas (n = 27), and nevi (n = 43)) provides insights into melanoma biology. Multivariate analysis reveals that PRKDC amplification is a prognostic molecule for melanomas. Further proteogenomic analysis combined with functional experiments reveals that the cis-effect of PRKDC amplification may lead to tumor proliferation through the activation of DNA repair and folate metabolism pathways. Proteome-based stratification of primary melanomas defines three prognosis-related subtypes, namely, the ECM subtype, angiogenesis subtype (with a high metastasis rate), and cell proliferation subtype, which provides an essential framework for the utilization of specific targeted therapies for particular melanoma subtypes. The immune classification identifies three immune subtypes. Further analysis combined with an independent anti-PD-1 treatment cohort reveals that upregulation of the MAPK7-NFKB signaling pathway may facilitate T-cell recruitment and increase the sensitivity of patients to immunotherapy. In contrast, PRKDC may reduce the sensitivity of melanoma patients to immunotherapy by promoting DNA repair in melanoma cells. These results emphasize the clinical value of multi-omics data and have the potential to improve the understanding of melanoma treatment.

Abstract Background The advances in deep learning-based pathological image analysis have invoked tremendous insights into cancer prognostication. Still, lack of interpretability remains a significant barrier to clinical application. Methods We established an integrative prognostic neural network for intrahepatic cholangiocarcinoma (iCCA), towards a comprehensive evaluation of both architectural and fine-grained information from whole-slide images. Then, leveraging on multi-modal data, we conducted extensive interrogative approaches to the models, to extract and visualize the morphological features that most correlated with clinical outcome and underlying molecular alterations. Results The models were developed and optimized on 373 iCCA patients from our center and demonstrated consistent accuracy and robustness on both internal (n = 213) and external (n = 168) cohorts. The occlusion sensitivity map revealed that the distribution of tertiary lymphoid structures, the geometric traits of the invasive margin, the relative composition of tumor parenchyma and stroma, the extent of necrosis, the presence of the disseminated foci, and the tumor-adjacent micro-vessels were the determining architectural features that impacted on prognosis. Quantifiable morphological vector extracted by CellProfiler demonstrated that tumor nuclei from high-risk patients exhibited significant larger size, more distorted shape, with less prominent nuclear envelope and textural contrast. The multi-omics data (n = 187) further revealed key molecular alterations left morphological imprints that could be attended by the network, including glycolysis, hypoxia, apical junction, mTORC1 signaling, and immune infiltration. Conclusions We proposed an interpretable deep-learning framework to gain insights into the biological behavior of iCCA. Most of the significant morphological prognosticators perceived by the network are comprehensible to human minds. Graphical Abstract

Abstract Hybrid mapping is a powerful approach to efficiently identify and characterize genes regulated through mechanisms in cis. In this study, using reciprocal crosses of the phenotypically divergent Duroc and Lulai pig breeds, we perform a comprehensive multi-omic characterization of regulatory variation across the brain, liver, muscle, and placenta through four developmental stages. We produce one of the largest multi-omic datasets in pigs to date, including 16 whole genome sequenced individuals, as well as 48 whole genome bisulfite sequencing, 168 ATAC-Seq and 168 RNA-Seq samples. We develop a read count-based method to reliably assess allele-specific methylation, chromatin accessibility, and RNA expression. We show that tissue specificity was much stronger than developmental stage specificity in all of DNA methylation, chromatin accessibility, and gene expression. We identify 573 genes showing allele specific expression, including those influenced by parent-of-origin as well as allele genotype effects. We integrate methylation, chromatin accessibility, and gene expression data to show that allele specific expression can be explained in great part by allele specific methylation and/or chromatin accessibility. This study provides a comprehensive characterization of regulatory variation across multiple tissues and developmental stages in pigs.

Abstract Multichannel meta-imaging, inspired by the parallel-processing capability of neuromorphic computing, offers considerable advancements in resolution enhancement and edge discrimination in imaging systems, extending even into the mid- to far-infrared spectrum. Currently typical multichannel infrared imaging systems consist of separating optical gratings or merging multi-cameras, which require complex circuit design and heavy power consumption, hindering the implementation of advanced human-eye-like imagers. Here, we present printable graphene plasmonic photodetector arrays driven by a ferroelectric superdomain for multichannel meta-infrared imaging with enhanced edge discrimination. The fabricated photodetectors exhibited multiple spectral responses with zero-bias operation by directly rescaling the ferroelectric superdomain instead of reconstructing the separated gratings. We also demonstrated enhanced and faster shape classification (98.1%) and edge detection (98.2%) using our multichannel infrared images compared with single-channel detectors. Our proof-of-concept photodetector arrays simplify multichannel infrared imaging systems and offer potential solutions in efficient edge detection in human-brain-type machine vision.

DNA has emerged as a promising storage medium to meet the soaring need for archival data storage because of its exceptional storage density and stability. However, current DNA‐based data storage systems are incompetent of achieving high‐quality random multiplexed access and frequently accessed data storage, which impedes its practical applications. Here, a dual‐mode storage system is proposed that combines DNA‐based archival data and nanodot‐based active data. This novel data‐storage system is constructed by writing the active and archival data on the same substrate through a facile two‐step process involving scanning probe lithography (SPL), DNA synthesis, and chemical immobilization. The data files are categorized and stored orderly in different microregions of the substrate to achieve efficient random access. On each microregion, the nanodot array stores not only the concise information for the archival DNA data but also contains the corresponding primer sequence. Such interrelation between active and archival data allows for facilely data reading by efficient microscopic modalities and in situ polymerase chain reaction (PCR). Facilitated by the integration of nanodot and DNA, this novel dual‐mode storage system demonstrates efficient data access and the potential of excellent storing capacity, paving the way for the advancement of DNA‐based data storage.

During pregnancy, the maternal body undergoes a series of adaptative physiological changes, leading to a slight increase in serum bile acid (BA) levels. Although the fetal liver can synthesize BAs since the first trimester through the alternative pathway, the BA metabolic system is immature in the fetus. Compared to adults, the fetus has a distinct composition of BA pool and limited expression of BA synthesis enzymes and transporters. Besides, the “enterohepatic circulation” of BAs is absent in fetus. Thus, fetal BAs need to be transported to the mother through the placenta for further metabolism and excretion, and maternal BAs can also be transported to the fetus. That is what we call the “fetal-placental-maternal BA circulation”. Various BA transporters and nuclear receptors are essential for maintaining the balance of this BA circulation to ensure normal fetal development. However, prenatal adverse environments can alter fetal BA metabolism, resulting in intrauterine developmental abnormalities and susceptibility to a variety of adult chronic diseases. This review summarizes the current understanding of the fetal-placental-maternal BA circulation and discusses the effects of prenatal adverse environments on this particular BA circulation, aiming to provide a theoretical basis for exploring early prevention and treatment strategies for BA metabolism-associated adverse pregnancy outcomes and long-term impairments.

The intestinal tract plays an important role in digestion and absorption, nutrient metabolism, and immune anti-stress. At the same time, the intestine is also the major site for pathogens and various harmful substances to invade. Probiotics, as living microbial agents, improve animal health by maintaining the microecological balance of the host's intestinal flora. To explore the protective effect of Clostridium butyricum (CB) on the gut, we investigated the changes in digestion, antioxidant, and gut microbiota in juvenile largemouth bass. The fish were fed with diets containing 0 (control, CB0), 4.3×108 (CB1), 7.5×108 (CB2), 1.5×109 (CB3), and 3.2×109 (CB4) CFU/kg Clostridium butyricum for 56 days. After 56 days of dietary supplementation with 4.3×108 and 3.2×109 CFU/kg of CB, significant growth promotion and feed utilization improvement were observed in largemouth bass (P < 0.05). The activities of digestive enzymes (trypsin, protease and amylase) and intestinal functional indicators (sodium-potassium ATP, γ-GT and CK) were significantly increased in the intestine of largemouth bass (P < 0.05). The contents of intestinal short-chain fatty acids (acetic acid, propionic acid, isobutyric acid, N-butyric acid and isovaleric acid) in largemouth bass were significantly increased (P < 0.05). CB significantly increased the activities of antioxidant enzymes (T-AOC, CAT, POD, GSH-Px and SOD) and decreased the content of MDA in the intestine of largemouth bass (P < 0.05). It was also observed that CB significantly increased the activities of immune-related markers lysozyme and alkaline phosphatase (P < 0.05). High-throughput sequencing of the 16 S rRNA gene in largemouth bass revealed a significant increase in gut microbial richness. KEGG pathway analysis showed that CB had significant effects on intestinal microbiota functions, such as nutrient metabolism and energy conversion. The results showed that CB could stimulate intestine to produce the organic product butyric acid, which was customized in the gut to enhance digestive performance, promote nutrient metabolism, and protect microbial homeostasis in the intestinal tract of largemouth bass. These results provide new insights into the protective effects of CB on the intestinal tract of aquatic animals.

Abstract Cuproptosis is a newly discovered form of programmed cell death significantly depending on the transport efficacy of copper (Cu) ionophores. However, existing Cu ionophores, primarily small molecules with a short blood half‐life, face challenges in transporting enough amounts of Cu ions into tumor cells. This work describes the construction of carrier‐free nanoparticles (Ce6@Cu NPs), which self‐assembled by the coordination of Cu2+ with the sonosensitizer chlorin e6 (Ce6), facilitating sonodynamic‐triggered combination of cuproptosis and ferroptosis. Ce6@Cu NPs internalized by U87MG cells induce a sonodynamic effect and glutathione (GSH) depletion capability, promoting lipid peroxidation and eventually inducing ferroptosis. Furthermore, Cu+ concentration in tumor cells significantly increases as Cu2+ reacts with reductive GSH, resulting in the downregulation of ferredoxin‐1 and lipoyl synthase. This induces the oligomerization of lipoylated dihydrolipoamide S‐acetyltransferase, causing proteotoxic stress and irreversible cuproptosis. Ce6@Cu NPs possess a satisfactory ability to penetrate the blood‐brain barrier, resulting in significant accumulation in orthotopic U87MG‐Luc glioblastoma. The sonodynamic‐triggered combination of ferroptosis and cuproptosis in the tumor by Ce6@Cu NPs is evidenced both in vitro and in vivo with minimal side effects. This work represents a promising tumor therapeutic strategy combining ferroptosis and cuproptosis, potentially inspiring further research in developing logical and effective cancer therapies based on cuproptosis.

Abstract Soft tissue sarcoma is a broad family of mesenchymal malignancies exhibiting remarkable histological diversity. We portray the proteomic landscape of 272 soft tissue sarcomas representing 12 major subtypes. Hierarchical classification finds the similarity of proteomic features between angiosarcoma and epithelial sarcoma, and elevated expression of SHC1 in AS and ES is correlated with poor prognosis. Moreover, proteomic clustering classifies patients of soft tissue sarcoma into 3 proteomic clusters with diverse driven pathways and clinical outcomes. In the proteomic cluster featured with the high cell proliferation rate, APEX1 and NPM1 are found to promote cell proliferation and drive the progression of cancer cells. The classification based on immune signatures defines three immune subtypes with distinctive tumor microenvironments. Further analysis illustrates the potential association between immune evasion markers (PD-L1 and CD80) and tumor metastasis in soft tissue sarcoma. Overall, this analysis uncovers sarcoma-type-specific changes in proteins, providing insights about relationships of soft tissue sarcoma.

Bidirectional interlinking converter (BIC) is the core equipment in a hybrid AC/DC microgrid connected between AC and DC sub-grids. However, the variety of control modes and flexible bidirectional power flow complicate the influence of AC faults on BIC itself and on DC sub-grid, which potentially threaten both converter safety and system reliability. This study first investigates AC fault influence on the BIC and DC bus voltage under different BIC control modes and different pre-fault operation states, by developing a mathematical model and equivalent sequence network. Second, based on the analysis results, a general accommodative current limiting strategy is proposed for BIC without limitations to specific mode or operation condition. Current amplitude is predicted and constrained according to the critical requirements to protect the BIC and relieving the AC fault influence on the DC bus voltage. Compared with conventional methods, potential current limit failure and distortions under asymmetric faults can also be avoided. Finally, experiments verify feasibility of the proposed method.

Abstract Objective The outbreak of the COVID-19 pandemic has drawn attention from all sectors of society to the level of public health services. This study aims to investigate the level of public health service supply in the four major regions of Guangdong Province, providing a basis for optimizing health resource allocation. Methods This article uses the entropy method and panel data of 21 prefecture-level cities in Guangdong Province from 2005 to 2021 to construct the evaluation index system of public health service supply and calculate its supply index. On this basis, the standard deviation ellipse method, kernel density estimation, and Markov chain are used to analyze the spatiotemporal evolution trend of the public health service supply level in Guangdong Province. The Dagum Gini coefficient and panel regression model are further used to analyze the relative differences and the key influencing factors of difference formation. Finally, the threshold effect model is used to explore the action mechanism of the key factors. Results Overall, the level of public health service supply in Guangdong Province is on an upward trend. Among them, polarization and gradient effects are observed in the Pearl River Delta and Eastern Guangdong regions; the balance of public health service supply in Western Guangdong and Northern Mountainous areas has improved. During the observation period, the level of public health services in Guangdong Province shifted towards a higher level with a smaller probability of leapfrogging transition, and regions with a high level of supply demonstrated a positive spillover effect. The overall difference, intra-regional difference and inter-regional difference in the level of public health service supply in Guangdong Province during the observation period showed different evolutionary trends, and spatial differences still exist. These differences are more significantly positively affected by factors such as the level of regional economic development, the degree of fiscal decentralization, and the urbanization rate. Under different economic development threshold values, the degree of fiscal decentralization and urbanization rate both have a double threshold effect on the role of public health service supply level. Conclusion The overall level of public health service supply in Guangdong Province has improved, but spatial differences still exist. Key factors influencing these differences include the level of regional economic development, the degree of fiscal decentralization, and the urbanization rate, all of which exhibit threshold effects. It is suggested that, in view of the actual situation of each region, efforts should be made to build and maintain their own advantages, enhance the spatial linkage of public health service supply, and consider the threshold effects of key factors in order to optimize the allocation of health resources.

Abstract The recently discovered kagome superconductors offer a promising platform for investigating intertwined orders and novel states, including topology, superconductivity, charge density waves, and more. The interplay among these orders can spontaneously break rotational symmetry, giving rise to exotic phenomena such as nematicity or even nematic superconductivity. Here we present our findings on the two-fold symmetric superconductivity in thin-flake RbV3Sb5 in response to direction-dependent in-plane magnetic fields, in contrast to the inherent six-fold structural symmetry of the crystal lattice. The two-fold symmetry was evidenced through a combination of magnetoresistance transport experiments, critical magnetic field measurements, and observations of anisotropic superconducting gaps. Additionally, by altering the experimental configuration, we also detected the presence of six-fold symmetric components superimposed on the two-fold symmetry at the boundary between normal and superconducting states. Our results underscore the correlation-driven symmetry-breaking phenomena and emphasize the potential of this correlated kagome family as a promising platform for investigating intertwined orders, including unconventional superconductivity.

In order to further understand the characteristics of phytoplankton community in the sea area near Changbiao Island in Xiapu, the data of phytoplankton and water environment from four cruises in May (spring), September (summer), December (autumn) and February (winter) in 2019—2020 were analyzed, and the characteristics of phytoplankton community structure were analyzed. The main environmental factors affecting the structure of phytoplankton community were studied by redundancy analysis. The results showed that there were 170 species of phytoplankton in 60 genera, 48 genera and 131 species of diatoms, 26 species of dinoflagellates in 10 genera, 2 species of cyanobacteria in 1 genera and 1 species of diatoms in 1 genera. Phytoplankton are mainly coastal wide-temperature and wide-salt species and warm water species. There are 13 dominant species throughout the year. In spring, Prorocentrum donghaiense and Noctiluca are the main species, and Skeletonema costatum and Siegesbeckia qiongshi are the main species in summer, autumn and winter. The spatial distribution of phytoplankton abundance shows a trend of high nearshore, low farshore, low in the south, and high in the north. Seasonal variation of phytoplankton is mainly affected by water temperature. Appropriate temperature and nutrients in spring and summer promote a large increase in phytoplankton, while autumn and winter are mainly affected by temperature. Now in spring and summer, the coastal nuclear power station of Changbiao Island in Xiapu should focus on monitoring the occurrence of red tide in spring and summer.

ABSTRACTUltrasonic-assisted enzymatic extraction (UAEE) technology was employed to extract the polysaccharides from Dendrobium offcinale Kimura et Migo (D. offcinale). The extraction conditions were optimized by central composite design (CCD) found in the response surface methodology (RSM). The polysaccharide yield (34.05 ± 1.03%) was well matched with the predicted value, as obtained under the optimum parameters: enzyme activity of 2040 U/g, a liquid-solid ratio of 71 mL/g, and a time of 84 min. Compared to other extraction methods, UAEE was able to yield D. offcinale polysaccharide (DOP) highly efficiently in a shorter extraction time period and at a lower extraction temperature. The extracted polysaccharide (DOPUAEE) showcased a better nitrite scavenging ability, a high antioxidant activity, and more potency in inhibiting α-glucosidase, expanding its versatility in food applications.

This work presents a facile way to fabricate a polymer/ceramics composite gel electrolyte to improve the overall properties of lithium-ion batteries. Lithium salt-grafted silica was synthesized and mixed with P(VDF-HFP) to produce a nanofiber film by the electrostatic spinning method. After coating a layer of SiO2 onto the surface of nanofibers through a sol-gel method, a composite nanofiber film was obtained. It was then immersed in plasticizer until saturation to make a composite gel electrolyte film. Electrochemical test results showed that the obtained gel electrolyte film shows high thermal stability (~450 °C), high ionic conductivity of 1.3 × 10−3 S cm−1 at 25 °C and a lithium-ion transference number of 0.58, and superior cycling stability, providing a new direction for manufacturing secondary batteries with higher safety and performance.

Lateolabrax maculatus iridovirus (LMIV) is a variant strain of red sea bream iridovirus (RSIV), causing serious economic losses in aquaculture. Claudins (CLDNs) are major components of tight junctions (TJs) forming an important line of defense against pathogens. Our pilot miRNA-mRNA joint analysis indicated the degradation of CLDN3, as well as its interaction with miR-181a during LMIV infection. To elucidate the miR-181a/CLDN3/LMIV interactions, in vitro assays were carried out on LMB-L cells. We first confirmed that LMIV infection could decrease the expression of CLDN3, accompanied by the enhancement of permeability, suggesting the dysfunction of TJs. Contrary to the inhibition of CLDN3, the activation of miR-181a was proved, presenting a negative correlation between miR-181a and CLDN3 (Pearson r = −0.773 and p < 0.01). In addition, the influence of CLDN3 on LMIV replication was analyzed by knockdown and over-expression of CLDN3. When CLDN3 was silenced in LMB-L cells with siCLDN3-623 at 9 days post transfection (dpt), LMIV copies and titers were significantly up-regulated by 1.59-fold and 13.87-fold, respectively. By contrast, LMIV replication in LMB-L cells was reduced by 60% and 71%, post transfection with pcDNA3.1-CLDN3 over-expressed plasmid at 6 dpt and 9 dpt, respectively. Ultimately, the regulatory relationship between miR-181a and CLDN3 was further validated by dual luciferase reporter assays. Taking into account the above-described results, we proposed a “miR-181a/CLDN3/LMIV” regulatory relationship. This study provides a new insight for understanding the mechanism of LMIV replication.

Background: We explore the association between leucocyte telomere length (LTL) and all-cause and cardiovascular disease (CVD)-specific death in CVD patients. Methods: We acquired 1599 CVD patients from a nationally representative US population survey for this study. We applied Kaplan–Meier curves, adjusted weighted Cox regression models, and restricted cubic spline to investigate the association between LTL and all-cause death. Additionally, we employed competing risk regression to assess the impact of LTL on cardiovascular-specific death, setting non-cardiovascular death as a competing event. Results: The overall mortality rate was 31.0% after a median follow-up of 13.9 years. Patients with shorter LTL exhibited a higher risk of all-cause death, with an adjusted hazard ratio (HR) of 1.25 (95% confidence interval (CI): 1.05–1.48). Restricted cubic spline illustrated a linear dose-response relationship. In gender-specific analyses, female patients with shorter LTL showed a higher risk of death (weighted HR, 1.79; 95% CI, 1.29–2.48), whereas this association was not observed in males (weighted HR, 0.90; 95% CI, 0.61–1.32). The Fine–Gray competing risk model revealed no significant relationship between LTL and cardiovascular-specific mortality but a significant association with non-cardiovascular death (adjusted HR, 1.24; 95% CI, 1.02–1.51). Conclusions: LTL is inversely associated with all-cause death in female CVD patients. The significant correlation between reduced LTL and increased all-cause mortality emphasizes LTL as a potential marker for tertiary prevention against cardiovascular disease.

Renovascular hypertension (RH), a secondary hypertension, can significantly impact heart health, resulting in heart damage and dysfunction, thereby elevating the risk of cardiovascular diseases. Coniferol (CA), which has vascular relaxation properties, is expected to be able to treat hypertension-related diseases. However, its potential effects on cardiac function after RH remain unclear. In this study, in combination with network pharmacology, the antihypertensive and cardioprotective effects of CA in a two-kidney, one-clip (2K1C) mice model and its ability to mitigate angiotensin II (Ang II)-induced hypertrophy in H9C2 cells were investigated. The findings revealed that CA effectively reduced blood pressure, myocardial tissue damage, and inflammation after RH. The possible targets of CA for RH treatment were screened by network pharmacology. The interleukin-17 (IL-17) and tumor necrosis factor (TNF) signaling pathways were identified using a Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The inflammatory response was identified using a Gene Ontology (GO) enrichment analysis. Western blot analysis confirmed that CA reduced the expression of IL-17, matrix metallopeptidase 9 (MMP9), cyclooxygenase 2 (COX2), and TNF α in heart tissues and the H9C2 cells. In summary, CA inhibited cardiac inflammation and fibrohypertrophy following RH. This effect was closely linked to the expression of MMP9/COX2/TNF α/IL-17. This study sheds light on the therapeutic potential of CA for treating RH-induced myocardial hypertrophy and provides insights into its underlying mechanisms, positioning CA as a promising candidate for future drug development.

Summary: Mating behavior is an essential fitness trait. We used the inbred, sequenced lines of the Drosophila Genetic Reference Panel (DGRP) to gain insights into the evolution of mating success and to evaluate the overlap in genetic architecture of mating behavior between the sexes. We found significant genetic variation for mating success when DGRP males and females from the same line were mated together, and when DGRP males and females were mated to an unrelated strain of the opposite sex. The mating success of DGRP males and females was not correlated when they were paired with the unrelated strain, suggesting independent genetic architecture of mating success in males and females that was confirmed by genome-wide association analyses. However, the mating success between pairs of the same or different DGRP lines was predicted accurately by the respective female and male mating success with the unrelated line.

This study focuses on understanding family electricity consumption behaviors in response to income and price changes from 1994 to 2022 across 12 prominent European countries. We employ a unique econometric approach, Auto-selection Models, to analyze the nuances of energy demand elasticity. Our methodology includes the use of saturation techniques, which are highly effective in identifying anomalies and discontinuities in the data, ensuring the reliability of our results. The Auto-metrics method streamlines the model selection process and enhances the accuracy of elasticity predictions. We use Error Correction Models (ECMs) for each country to examine the long-term equilibrium relationships among key variables such as energy consumption, household income, electricity prices, and weather patterns, taking into account any observed anomalies and significant structural changes. The findings reveal varying levels of income and price elasticity across the countries, reflecting their unique economic and climatic conditions. The study's results hold significant implications for policymaking. By recognizing and adapting to the varied characteristics of electricity demand elasticity, energy policies can be more accurately tailored at both the national and European Union levels.

Abstract Background Fabry disease (FD) is an X-linked, hereditary dysfunction of glycosphingolipid storage caused by mutations in the GLA gene encoding alpha-galactosidase A enzyme. In rare cases, FD may coexist with immunoglobulin A nephropathy (IgAN). We describe a case of concurrent FD, IgAN, and dilated cardiomyopathy-causing mutations in the TTN and BAG3 genes, which has not been reported previously. Case presentation A 60-year-old female patient was admitted with a one-week history of facial and lower-limb edema, two-year history of left ventricular hypertrophy and sinus bradycardia, and recurring numbness and pain in three lateral digits with bilateral thenar muscle atrophy. Renal biopsy revealed concurrent FD (confirmed via an alpha-galactosidase A enzyme assay, Lyso-GL-3 quantification, and GLA gene sequencing) and IgAN. Heterozygous mutations in the TTN (c.30,484 C > A;p.P10162T) and BAG3 (c.88 A > G;p.I30V) genes were observed. The patient reported that two of her brothers had undergone kidney transplantation; one died suddenly at 60 years of age, and the other required a cardiac pacemaker. The 35-year-old son of the patient was screened for the GLA gene mutation and found to be positive for the same mutation as the patient. The patient was administered oral losartan (50 mg/day). Enzyme replacement therapy was refused due to financial reasons. Her renal and cardiac functions were stable yet worth closely monitoring during follow-up. Conclusion The family history of patients with concurrent heart and renal diseases should be assessed in detail. Genetic testing and histological examinations are essential for diagnosing FD with IgAN.

Abstract Shading in combination with extended photoperiods can cause exaggerated stem elongation (ESE) in soybean, leading to lodging and reduced yields when planted at high-density in high-latitude regions. However, the genetic basis of plant height in adaptation to these regions remains unclear. Here, through a genome-wide association study, we identify a plant height regulating gene on chromosome 13 (PH13) encoding a WD40 protein with three main haplotypes in natural populations. We find that an insertion of a Ty1/Copia-like retrotransposon in the haplotype 3 leads to a truncated PH13H3 with reduced interaction with GmCOP1s, resulting in accumulation of STF1/2, and reduced plant height. In addition, PH13 H3 allele has been strongly selected for genetic improvement at high latitudes. Deletion of both PH13 and its paralogue PHP can prevent shade-induced ESE and allow high-density planting. This study provides insights into the mechanism of shade-resistance and offers potential solutions for breeding high-yielding soybean cultivar for high-latitude regions.

Edible mushrooms are well received by consumers due to their various nutrients and tasty. However, mushrooms are prone to cap opening, browning, rotten and other deterioration phenomena after harvest, which severely limits the development of mushrooms industry. Therefore,this paper summarizes the quality evaluation factors of mushrooms, including sensory quality, intrinsic quality and safety. As an example, the preservation technologies of Agaricus bisporus are summarized, including physical preservation (low temperature preservation, modified atmosphere preservation, radiation preservation, dehydration treatment preservation, magnetic field preservation and electrostatic field preservation), chemical preservation (chemical preservatives preservation, ozone preservation, electrolyzed water and plasma-activated water preservation) and biological preservation (biological coating preservation, plant extracts preservation, microbial preservatives preservation and antagonistic bacteria preservation). The application of preservation technologies in mushrooms is also summarized. The shortcomings in the current quality evaluation and preservation technologies of mushrooms are put forward. The development of the quality evaluation and preservation of mushrooms is prospected in order to promote the progress and development of mushrooms industry in the future.

Photodetectors converting light into electrical signals are crucial in various applications. The pursuit of high-performance photodetectors with high sensitivity and broad spectral range simultaneously has always been challenging in conventional semiconductor materials. Graphene, with its zero bandgap and high electron mobility, is an attractive candidate, but its low light absorption coefficient restricts its practical application in light detection. Integrating graphene with light-absorbing materials like PbS quantum dots (QDs) can potentially enhance its photodetection capabilities. Here, this work presents a broadband photodetector with enhanced sensitivity based on a graphene–PbS QD heterostructure. The device leverages the high carrier mobility of graphene and the strong light absorption of PbS QDs, achieving a wide detection range from ultraviolet to near-infrared. Employing a simple spinning method, the heterostructure demonstrates ultrahigh responsivity up to the order of 107 A/W and a specific detectivity on the order of 1013 Jones, showcasing significant potential for photoelectric applications.

Glabridin is a widely used product in the cosmetics and pharmaceutical industry, which is generally isolated and purified from Licorice (Glycyrrhiza glabra) extract in industrial production. It has wide clinical applications, but significant toxicity has also been reported. The purity of glabridin raw material is generally between 90% and 98%. We have identified a toxic impurity, glabrene, in the industrial product glabridin. Our investigation using an AB wild-type zebrafish toxicity test showed that glabrene has a significant lethal effect with an LC10 of 2.8 μM. Glabrene induced obvious malformation and disrupted cartilage development in zebrafish larvae. Furthermore, the compound significantly reduced larval mobility and caused damage to brain neural tissues. Metabolic pathway analysis and neurotransmitter quantification via ELISA indicated abnormal activation of the phenylalanine metabolic pathway, resulting in elevated dopamine and acetylcholine levels in vivo. These findings provide insights into the potential risks of glabrene contamination and offer a new reference point for enhancing safety measures and quality controls in licorice-derived products.

Lentinula edodes (L. edodes) is a globally popular edible mushroom because of its characteristic sulfur-containing flavor compounds. However, the formation of the volatile sulfur-containing compounds in the mycelium of L. edodes has not been studied. We found that there were also sulfur-containing aroma compounds in the mycelium of L. edodes, and the content and composition varied at different stages of mycelial growth and development. The γ-glutamyl-transpeptidase (GGT) and cysteine sulfoxide lyase (C-S lyase) related to the generation of sulfur compounds showed the highest activities in the 15-day sample. Candidate genes for the metabolism of volatile sulfur compounds in mycelium were screened using transcriptome analysis, including encoding the GGT enzyme, C-S lyase, fatty acid oxidase, HSP20, and P450 genes. The expression patterns of Leggt3 and Leccsl3 genes were consistent with the measured activities of GGT and C-S lyase during the cultivation of mycelium and molecular dynamics simulations showed that they could stably bind to the substrate. Our findings provide insights into the formation of sulfur-containing flavor compounds in L. edodes. The mycelium of L. edodes is suggested for use as material for the production of sulfur-containing flavor compounds.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12890-021-01657-6.

【Objective】In order to provide reference for the application of condensed tannins in Micropterus salmoides feed, this study was conducted to assess the effects of short-term feeding condensed tannins on growth performance and liver health of large-sized M. salmoides.【Method】A total of 600 fish with an initial weight of 510 (±10.4) g were selected and randomly divided into 4 groups, with 3 replicates per group and 50 fish per replicates. Fish in the control group were fed with basic diet (G1), while fish in the experimental groups were fed with basic diet supplemented with 0.1% (G2), 0.2% (G3) and 0.4% (G4) of condensed tannins, respectively. The experimental period was 30 d.【Result】Compared with G1, the feed coefficient of fish in G4 was significantly increased by 17.44% (P < 0.05), while the survival rate was significantly decreased by 15.79% (P < 0.05); The abdominal fat rate of fish in G2, G3, and G4 were significantly decreased by 12.03%, 16.18%, and 13.69% respectively (P < 0.05). There was no significant difference in feed intake, weight gain rate, specific growth rate among all groups; The contents of serum glucose, total cholesterol, and triglycerides of fish in G4 were significantly decreased by 49.73%, 28.46% and 35.71%, respectively (P < 0.05), while the contents of serum low-density lipoprotein cholesterol of fish in G3 and G4 were significantly decreased by 38.71% and 51.61% respectively (P < 0.05). There was no significant difference in the contents of albumin, globulin, high-density lipoprotein cholesterol and the activities of alanine transaminase and glutamic transaminase among all groups; With the increase of dietary condensed tannins, the "fatty liver" status of large-sized M. salmoides was improved, the vacuolation and inflammatory infiltration of liver tissue were also weakened, and the liver lipid content and lipid droplet area ratio were significantly reduced.【Conclusion】Dietary supplemented with 0.1% and 0.2% of condensed tannins had no significant effects on the survival rate and feed coefficient of large-sized M. salmoides. However, it could promote the metabolism of glucose and lipid, reduce liver fat and abdominal fat, and improve liver health of fish. If the evaluation is based on liver health, the appropriate concentration of condensed tannins in the diet of M. salmoides is 0.2%.

Abstract The booming growth of cloud manufacturing services provides users with more choices. However, cloud manufacturing service recommendation remains a challenging issue due to numerous similar candidate services and diverse user preferences. The purpose of this paper is to provide an efficient and accurate cloud manufacturing service recommendation method. A spectral clustering algorithm is first designed to cluster the cloud manufacturing services. Then the candidate rating service set is constructed based on the service clusters by service function comparison and parameter matching. Finally, an improved Slope one algorithm, which integrates user similarity and service similarity, is proposed to rate the cloud manufacturing services. The top-k services with the highest scores are recommended to the users. Experiments show that the proposed method can provide more accurate service rating with less time consumption. The service recommendation performance of this method is also proved to be superior to other methods in terms of precision, recall, and F-score.

Ductile Cu–Al–Mn shape memory alloys obtain the damping capacity through the movement of martensite boundaries. To reduce the number of vacancies at martensite boundaries can improve their damping capacity. Our results showed that Ni alloying could remarkably suppress the vacancy movement during the process of cooling from high temperature and heating as well as ageing. The Cu-18.0Al-8.4Mn-2.5Ni alloy showed remarkably higher damping capacity than the Cu-18.0Al-9.4Mn alloy did due to the reduced vacancies at martensite boundaries by the Ni alloying, regardless of the direct quenching, up-quenching, and step-quenching. The occurrence of martensitic stabilization could rationalize the lower improvement of damping capacity in the up-quenched Cu-18.0Al-9.4Mn alloy. The present results also further confirmed that the original number of vacancies at the martensite boundaries determined the occurrence of martensitic stabilization.

Objective: The protective effect of polyphenol of lotus seed epicarp on HepG2 oxidative stress damage induced by tert-butylhydro-peroxide (T-BHP) was investigated. Method: The concentration of T-BHP with a survival rate close to 50% was selected as the concentration for establishing the oxidative damage model. To evaluate the anti-oxidative stress activity levels of polyphenol of lotus seed epicarp at different concentrations (2.5, 5, and 7.5 μg/mL), cell viability, reactive oxygen species (ROS), malondialdehyde (MDA), lactic dehydrogenase (LDH), glutathione (GSH) and antioxidant enzyme-related gene expression were used as evaluation indicators, and tea polyphenol was used as the positive control. Result: When 120 μmol/L concentration of T-BHP was established for 4 h, the cell survival rate reached 49.18%±7.55%, which met the requirements of model construction. Therefore, 120 μmol/L was selected as the modeling concentration of the oxidative damage model for subsequent experiments. The polyphenol from lotus seed epicarp significantly inhibited the decrease of cell survival rate induced by T-BHP (P

To verify the effect of storage temperature on the preservation of Stropharia rugoso-annula, fresh Stropharia rugoso-annulata was stored at different temperatures (0, 15 ℃) for 12 days, and the cap opening rate, decay rate, weight loss rate, color, hardness, chewiness and volatile flavor compounds were determinated at regular time. The results showed that fresh Stropharia rugoso-annulata could be stored at 15 ℃ for about 4~6 days while exhibited good quality after storage for 12 days at 0 ℃. Compared with 15 ℃, Stropharia rugoso-annulata storage at 0 ℃ had lower cap opening rate, decay rate and weight loss rate, and higher hardness, chewiness and color. After 12 days of storage at 0 ℃, the decay rate of Stropharia rugoso-annulata was 12.12%, which was significantly lower than that of 15 ℃ group (95.45%, P

Abstract The incidence of bladder cancer (BLCA) in men is higher than that in women. Differences in androgen levels between men and women are considered the main causes of incidence rate differences. In this study, dihydrotestosterone (DHT) significantly increased the proliferation and invasion of BLCA cells. In addition, BLCA formation and metastatic rates were higher in N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-treated male mice than in female and castrated male mice in vivo. However, immunohistochemistry showed that androgen receptor (AR) was expressed at low levels in normal and BLCA tissues of men and women. The classical AR pathway considers that DHT binds to AR and induces it to enter the nucleus, where it functions as a transcription factor. Here, a non-AR combination pathway of androgen that promoted BLCA development was investigated. The EPPK1 protein was bombarded with DHT, as determined by biotinylated DHT-binding pull-down experiments. EPPK1 was highly expressed in BLCA tissues, and EPPK1 knockdown significantly inhibited BLCA cell proliferation and invasion promoted by DHT. Moreover, JUP expression was elevated in DHT-treated high-EPPK1 expressing cells, and JUP knockdown inhibited cell proliferation and invasion. EPPK1 overexpression increased tumour growth and JUP expression in nude mice. Furthermore, DHT increased the expression of the MAPK signals p38, p-p38, and c-Jun, and c-Jun could bind to the JUP promoter. However, the promotion of p38, p-p38, and c-Jun expression by DHT was not observed in EPPK1 knockdown cells, and a p38 inhibitor suppressed the DHT-induced effects, indicating that p38 MAPK may be involved in the regulation of DHT-dependent EPPK1-JUP-promoted BLCA cell proliferation and invasion. The growth of bladder tumours in BBN-treated mice was inhibited by the addition of the hormone inhibitor goserelin. Our findings indicated the potential oncogenic role and mechanism of DHT in BLCA pathogenesis through a non-AR pathway, which may serve as a novel therapeutic target for BLCA.

ObjectiveMercury sphygmomanometer (MS) has now been less and less used and no new devices have been manufactured (according to Minamata convention 2013). The application of the electronic sphygmomanometer (ES) in clinical practice has become increasingly common. However, reliable evidence for the use of the ES in high-altitude areas remains scarce. The purpose of this study was to validate the applicability of the ES in high altitude areas.MethodsIn Luhuo County, Sichuan Province, China, 3,400 m above the sea level, two trained physicians measured the blood pressure (BP) of participants using both the mercury sphygmomanometer and the ES. Pearson correlation analysis and paired T-test, respectively, were used to compare the correlation and the difference between the BP values measured by the two devices. The applicability of the ES in high-altitude areas was evaluated according to the validation standards of the 2018 Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization (AAMI/ESH/ISO) Collaboration Statement.ResultsIn this study, 257 participants were included. There was a strong correlation between BP values measured by the two devices, with correlation coefficients for systolic blood pressure (SBP) and diastolic blood pressure (DBP) of 0.97 and 0.93, respectively. Compared with the MS, the ES tended to measure the subjects' DBP (76.21 ± 13.29 mmHg vs. 76.53 ± 14.07 mmHg; P = 0.557) accurately, but overestimate the SBP of the subjects (123.32 ± 22.25 mmHg vs. 121.34 ± 22.88 mmHg; P

A soft and tunable microwave bandpass Chebyshev microstrip end-coupled filter is demonstrated on a polydimethylsiloxane substrate based on high electrically conductive composites made of silver nanoparticle-covered flakes, even with large strain. To achieve a precise design, key microwave parameters such as the impedance, S-parameters, and transmission matrix are defined as a function of strain. This strain vector polar coordinate is used to represent the relationship between the type and the performance of a filter. Then, the most important Chebyshev or quasi-Chebyshev type of filter can be accurately realized by looking up its polar coordinates to find the corresponding strain magnitude and direction of stretching. An end-coupled Chebyshev microstrip bandpass filter with a center frequency of 12.8 GHz and bandwidth of 22% was designed and fabricated for demonstration. Experimentally, at a lateral elongation of 8% and 10.7%, the center frequency decreases by 0.61 and 0.88 dB, respectively, matching the simulation results very well. One potential application for this tunable filter is a front-end module mounted on the biomimetic robot driven by its mechanic movements.

Thromboembolism resulting from platelet dysfunction constitutes a significant contributor to the development of cardiovascular disease. Sirtuin 6 (SIRT6), an essential NAD+-dependent enzyme, has been linked to arterial thrombosis when absent in endothelial cells. In the present study, we have confirmed the presence of SIRT6 protein in anucleated platelets. However, the precise regulatory role of platelet endogenous SIRT6 in platelet activation and thrombotic processes has remained uncertain. Herein, we present compelling evidence demonstrating that platelets isolated from SIRT6-knockout mice (SIRT6−/−) exhibit a notable augmentation in thrombin-induced platelet activation, aggregation, and clot retraction. In contrast, activation of SIRT6 through specific agonist treatment (UBCS039) confers a pronounced protective effect on platelet activation and arterial thrombosis. Moreover, in platelet adoptive transfer experiments between wild-type (WT) and SIRT6−/− mice, the loss of SIRT6 in platelets significantly prolongs the mean thrombus occlusion time in a FeCl3-induced arterial thrombosis mouse model. Mechanistically, we have identified that SIRT6 deficiency in platelets leads to the enhanced expression and release of proprotein convertase subtilisin/kexin type 9 (PCSK9), subsequently activating the platelet activation-associated mitogen-activated protein kinase (MAPK) signaling pathway. These findings collectively unveil a novel protective role of platelet endogenous SIRT6 in platelet activation and thrombosis. This protective effect is, at least in part, attributed to the inhibition of platelet PCSK9 secretion and mitogen-activated protein kinase signaling transduction. Our study provides valuable insights into the intricate interplay between SIRT6 and platelet function, shedding light on potential therapeutic avenues for managing thrombotic disorders.

Foamed concrete, due to its lightweight and high-strength characteristics, offers significant advantages as a roadbed material. However, its mechanical properties are notably influenced by its density and microstructure. Comprehensive research addressing the correlation between the density, mechanical properties, and microstructure of roadbed foamed concrete, especially within real construction scenarios, remains limited. To address this research gap, we undertook compressive strength tests and a set of microstructural analyses on four sets foamed concrete samples of varying densities prepared on-site. The objective was to deeply understand the mechanical and microstructural characterization of roadbed foamed concrete at different densities and correlation Analysis. The findings indicate an exponential correlation between density and compressive strength, most prominently within the density range of 800–1000 kg/m3, accompanied by commendable thermal stability. X-ray Computed Tomography (X-CT) analyses further demonstrate that density increase is pivotal in enhancing the pore structure, thereby achieving lower porosity, fewer detrimental pores, more homogeneous pore distribution, and superior pore sphericity. Scanning Electron Microscopy (SEM) evaluations suggest that enhancing the density of the sample can mitigate the damage to individual pores, reduce internal cavities, and curb initial defects. Furthermore, the pore intersections exhibit a more intact and dense crystalline structure. Upon assessment, we discerned a significant correlation between porosity, compressive strength, and density. The Pearson correlation coefficient (r) between any two of these parameters is notably close to 1 (−1). These research results show that it is feasible to optimize the density of foam concrete to enhance its microstructure and thereby enhance its compressive performance. This provides strong data support for the wider application of foam concrete in roadbed engineering.

To enhance the adaptability of foam concrete in roadbed engineering, there is also a consideration to satisfy the increasing demand for sustainable and green building materials. This research examines the augmenting of the durability and mechanical properties of lightweight roadbed foam concrete (Basalt and Sisal fiber Lightweight Roadbed Foam Concrete - BSLRFC), through the incorporation of basalt and sisal fibers. A meticulous experimental investigation was executed on BSLRFC specimens, which comprised varying volume fractions (0.15%, 0.30%, and 0.45%) and disparate mixing ratios (2:1, 1:1, 1:2), to evaluate their mechanical, durability, and microscopic characteristics. The consequential observations indicate that the performance of the specimens manifests a pattern of initial improvement followed by a subsequent decline with the increasing volume fraction of the mixed fibers. Optimal mechanical attributes and durability performance were realized when the hybrid fibers volume fraction was calibrated at 0.3%, and an appropriate mixing ratio design was incorporated (with a basalt fiber to sisal fiber ratio of 1:2). The comprehensive microstructural analysis revealed the reinforced mechanism for the mechanical characteristics and longevity of the BSLRFC specimens. This provides strong data support for the wider application of BSLRFC in roadbed engineering.

Hydrogen (H2) gas is recognized for its anti-oxidative, anti-apoptotic, and anti-inflammatory properties in multiple plant and animal models. Nevertheless, there is a lack of research on the effects of H2 administration on fish. This research seeks to investigate how H2 administration affects the growth performance, mammalian target of rapamycin (mTOR) and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways, and intestinal microbiota of juvenile largemouth bass under normal feeding conditions. The research randomly allocated 240 fish (3.55 ± 0.01 g) into two treatment groups, each comprising 4 replicate tanks with 30 fish per tank. The control group was maintained in regular water, while the experimental group (referred to as H2 group) was treated with H2-dissolved water for 1 h per day for 6 weeks. Upon analysis of both groups, it was revealed that the weight gain, final weight, feed intake, specific growth rate, and survival rate were significantly improved by H2 treatment (P

Abstract Most patients with hypertension are complicated with insulin resistance (IR), which is one of the risk factors of hypertension and can increase the level of serum homocysteine (Hcy) by affecting Hcy's metabolic enzyme and insulin level. Investigations in recent years have shown that Hcy is an independent risk factor for cardiovascular diseases. At present, folic acid is the prominent medicine used to reduce Hcy, but its effection for Hcy has an obvious individual difference, which is closely related to individual genes. Moreover, folic acid is chiefly used in patients with Hcy ≥15 μmol/L, but Hcy ≥10 μmol/L has had an adverse effect on the cardiovascular system. Randomized clinical trials have shown that dapagliflozin can improve IR. Therefore, whether it can reduce Hcy has become a new direction. This study was a retrospective case–control study. Patients with high serum Hcy and hypertension complicated with IR were divided into two groups: the dapagliflozin group (n = 166) and the control group (n = 198). Before and after 12 weeks of treatment, the changes in serum Hcy and IR index were measured and compared. We found that dapagliflozin could reduce the serum Hcy level of patients with hypertension and IR to a certain extent. Dapagliflozin could be a viable option for hypertension complicated with IR and hyperhomocysteinemia. However, these findings need to be further confirmed in future randomized clinical trials with a large number of samples.

Abstract Genetic mapping to identify genes and alleles associated with or causing economically important quantitative trait variation in livestock animals such as pigs is a major goal in animal genetic improvement. Despite recent advances in high-throughput genotyping technologies, the resolution of genetic mapping in pigs remains poor due in part to the low density of genotyped variant sites. In this study, we overcame this limitation by developing a reference haplotype panel for pigs based on 2259 whole genome-sequenced animals representing 44 pig breeds. We evaluated software combinations and breed composition to optimize the imputation procedure and achieved an average concordance rate in excess of 96%, a non-reference concordance rate of 88%, and an r 2 of 0.85. We demonstrated in two case studies that genotype imputation using this resource can dramatically improve the resolution of genetic mapping. A public web server has been developed to allow the pig genetics community to fully utilize this resource. We expect this resource to facilitate genetic mapping and accelerate genetic improvement in pigs.

Abstract Background The digital economy based on the internet and IT is developing rapidly in China, which makes a profound impact on urban environmental quality and residents’ health activities. Thus, this study introduces environmental pollution as a mediating variable based on Grossman’s health production function to explore the impact of digital economic development on the health of the population and its influence path. Methods Based on the panel data of 279 prefecture-level cities in China from 2011 to 2017, this paper investigates the acting mechanism of digital economic development on residents’ health by employing a combination of mediating effects model and spatial Durbin model. Results The development of digital economy makes direct improvement on residents’ health condition, which is also obtained indirectly by means of environmental pollution mitigation. Besides, from the perspective of spatial spillover effect, the development of digital economy also has a significant promoting effect on the health of adjacent urban residents, and further analysis reveals that the promoting effect in the central and western regions of China is more pronounced than that in the eastern region. Conclusions Digital economy can have a direct promoting effect on the health of residents, and environmental pollution has an intermediary effect between digital economy and residents’ health; At the same time, there is also a regional heterogeneity among the three relationships. Therefore, this paper believes that the government should continue to formulate and implement scientific digital economy development policies at the macro and micro levels to narrow the regional digital divide, improve environmental quality and enhance the health level of residents.

Abstract Background Alternative splicing is an important step in gene expression, generating multiple isoforms for the same genes and greatly expanding the diversity of proteomes. Genetic variation in alternative splicing contributes to phenotypic diversity in natural populations. However, the genetic basis of variation in alternative splicing in livestock including pigs remains poorly understood. Results In this study, using a Duroc x Pietrain F2 pig population, we performed genome-wide analysis of alternative splicing estimated from stranded RNA-Seq data in skeletal muscle. We characterized the genetic architecture of alternative splicing and compared its basic features with those of overall gene expression. We detected a large number of novel alternative splicing events that were not previously annotated. We found heritability of quantitative alternative splicing scores (percent spliced in or PSI) to be lower than that of overall gene expression. In addition, heritabilities showed little correlation between alternative splicing and overall gene expression. We mapped expression QTLs (eQTLs) and splice QTLs (sQTLs) and found them to be largely non-overlapping. Finally, we integrated sQTL mapping with phenotype QTL (pQTL mapping to identify potential mediator of pQTL effect by alternative splicing. Conclusions Our results suggest that regulatory variation exists at multiple levels and that their genetic controls are distinct, offering opportunities for genetic improvement.

AbstractUnderstanding statistics is essential for engineers. However, statistics courses remain challenging for many students, as they find them rigid, abstract, and demanding. Prior research has indicated that using project-based learning (PjBL) to demonstrate the relevance of statistics to students can have a significant effect on learning in these courses. Consequently, this study sought to explore the impact of a PjBL intervention on student perceptions of the relevance of engineering and statistics. The purpose of the intervention was to help students understand the connection between statistics and their academic majors, lives, and future careers. Four mini-projects connecting statistics to students’ experiences and future careers were designed and implemented during a 16-week course and students’ perceptions were compared to those of students who took a traditional statistics course. Students enrolled in the experimental group (a synchronous learning experience) and the control group (an online learning experience) were sent the same survey at the end of the semester. The survey results suggest that the PjBL intervention could potentially increase students’ understanding of the usefulness of statistics and effectively enhance their perceptions of belonging to the engineering community. This study summarizes the results of this PjBL intervention, the limitations of the research design, and suggests implications for improving future statistics courses in the context of engineering.

Elastic spherical polishing tools effectively conform to the polishing surface and exhibit high efficiency in the removal of materials, so they are extensively used in the sub-aperture polishing stages of optical components. However, their processing is often accompanied by significant mid-spatial frequency (MSF) errors, which critically degrade the performance of optical systems. To suppress the MSF errors generated during polishing with spherical tools, this study investigates the influence factor of MSF errors during the polishing process through an analysis of the convolution effect in material removal. A material removal profile model is established, and a uniform removal simulation is conducted to assess the influence of different shape material removal profiles on MSF errors. Simulation and experimental results show that a Gaussian-like shape material removal profile is more effective in suppressing the MSF errors during polishing compared to the “W” and trapezoidal shape material removal profiles. In addition, based on the characteristics of the RMS decreasing in a serrated trend with the decrease in path spacing, a path spacing optimization method considering the polishing efficiency is proposed to improve the polishing efficiency while controlling the MSF errors, and the effectiveness of the path spacing optimization method is verified by comparing the MSF error at the maximum theoretical path spacing and the path spacing that is less than this. Finally, the path spacing optimization method is used to polish single-crystal silicon to further illustrate its practicality.

Severe acute pancreatitis (SAP), a widespread inflammatory condition impacting the abdomen with a high mortality rate, poses challenges due to its unclear pathogenesis and the absence of effective treatment options. Isorhamnetin (ISO), a naturally occurring flavonoid, demonstrates robust antioxidant and anti-inflammatory properties intricately linked to the modulation of mitochondrial function. However, the specific protective impact of ISO on SAP remains to be fully elucidated. In this study, we demonstrated that ISO treatment significantly alleviated pancreatic damage and reduced serum lipase and amylase levels in the mouse model of SAP induced by sodium taurocholate (STC) or L-arginine. Utilizing an in vitro SAP cell model, we found that ISO co-administration markedly prevented STC-induced pancreatic acinar cell necrosis, primarily by inhibiting mitochondrial ROS generation, preserving ATP production, maintaining mitochondrial membrane potential, and preventing the oxidative damage and release of mitochondrial DNA. Mechanistically, our investigation identified that high-temperature requirement A2 (HtrA2) may play a central regulatory role in mediating the protective effect of ISO on mitochondrial dysfunction in STC-injured acinar cells. Furthermore, through an integrated approach involving bioinformatics analysis, molecular docking analysis, and experimental validation, we uncovered that ISO may directly impede the histone demethylation activity of KDM5B, leading to the restoration of pancreatic HtrA2 expression and thereby preserving mitochondrial function in pancreatic acinar cells following STC treatment. In conclusion, this study not only sheds new light on the intricate molecular complexities associated with mitochondrial dysfunction during the progression of SAP but also underscores the promising value of ISO as a natural therapeutic option for SAP.

The aim of this study was to investigate the effects of sodium butyrate (SB) supplementation on growth performance, antioxidant enzyme activities, inflammatory factors, and hypoxic stress in largemouth bass (Micropterus salmoides). Diets were supplemented with different doses of SB at 0 (SB0), 0.5 (SB1), 1.0 (SB2) and 2.0 (SB3) g/kg. The hypoxic stress experiment was performed after 56 days of culture. The results showed that compared with the SB0 group, the final body weight, weight gain rate and protein deposition rate of the SB3 group were significantly increased (P