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BackgroundArsenic, cobalt, barium, and other individual metal exposure have been confirmed to be associated with the incidence of kidney stones. However, there are few studies on the association between mixed metal exposure and kidney stones, especially in occupational groups. ObjectiveTo investigate the association between mixed metal exposure and kidney stones in an occupational population from a metal smelting plant. MethodsA questionnaire survey was conducted to collect sociodemographic characteristics, medical history, and lifestyle information of 1158 mixed metal-exposed workers in a metal smelting plant in Guangdong Province from July 2021 to January 2022. Midstream morning urine samples were collected from the workers, the concentrations of 18 metals including lithium, vanadium, chromium, manganese, cobalt, nickel, copper, zinc, arsenic, selenium, strontium, molybdenum, cadmium, cesium, barium, tungsten, titanium, and lead were measured by inductively coupled plasma mass spectrometry, and the urinary mercury levels were measured by cold atomic absorption spectroscopy. Based on predetermined inclusion criteria, a total of 919 mixed metal-exposed workers were included in the study, including 117 workers in the kidney stone group and 802 workers in the non-kidney stone group. With a detection rate of urinary metals greater than 80% as entry criterion, 16 eligible metals were finally included for further analysis. Parametric or non-parametric methods were used to compare the differences between continuous or categorical variables of the non-kidney stone group and the kidney stone group. Logistic regression models were constructed to explore the association between individual metal exposures and kidney stones. Weighted quantile sum (WQS) regression models were used to evaluate the association between mixed metal exposure and kidney stones, as well as the weights of each metal on kidney stones. Then Bayesian kernel machine regression (BKMR) models were used to explore the overall effect of mixed metal exposure on renal calculi and the potential interactions between metals. ResultsWe found that there were significant differences in sex, age, length of service, and body mass Index (BMI) between the non-kidney stone group and the kidney stone group (P

Abstract Background Bile acids (BAs) concentration can affect metabolic improvement caused by bariatric surgery and BA concentrations increase in patients after sleeve gastrectomy (SG). Here, how BAs after SG affect metabolism in nonalcoholic fatty liver disease (NAFLD) was studied. Methods Mice were given high‐fat diet (HFD) to induce NAFLD and received SG surgery. Hepatic and fecal BA concentrations in mice were detected by liquid chromatography‐tandem mass spectrometry method. BA‐related genes were detected by quantitative real‐time polymerase chain reaction. G protein BA receptor 1 (GPBAR1) expression was identified using western blot analysis. NAFLD mice after SG received GPBAR1 inhibitor Triamterene. The weight of mice and mice liver was detected. Mouse liver tissue was observed by hematoxylin–eosin and Oil Red O staining. Triglyceride (TG), nonesterified fatty acid (NEFA), and cyclic adenosine monophosphate (cAMP) levels in mouse liver tissue were analyzed by metabolic assay and enzyme‐linked immune sorbent assay. Results SG boosted increase in hepatic total/conjugated BAs and related genes and GPBAR1 expression, and attenuated increase in fecal total BAs/muricholic acid in HFD‐induced mice and increased fecal taurine‐BAs in HFD‐induced mice. Triamterene (72 mg/kg) reversed the inhibitory role of SG in HFD‐induced increase of body weight, lipid accumulation, inflammatory cell infiltration, and increase of hepatic weight and TG/NEFA content, and counteracted the positive role of SG in HFD‐induced increase of hepatic cAMP concentration in mice. Conclusions BAs improve metabolism via activating GPBAR1 to increase cAMP in NAFLD mice after SG.

To improve the limited bioavailability of resveratrol (RSV) due to its poor water solubility, stability and bioaccessibility, there is an urgent need for the development of food-grade delivery systems. Herein, RSV was loaded into Spirulina platensis (SP) through passive diffusion, electrostatic and hydrogen bond interactions to create a Spirulina platensis (SP)-based edible vehicle called SP@RSV, with a maximum loading content of 45.36 ± 1.08 % and loading efficiency of 86.72 ± 4.41 %. RSV was endowed with ultraviolet resistance after loading. SP@RSV showed both a broad-spectrum scavenging capacity against free radicals after digestion of gastrointestinal fluids, and a high bioaccessibility. Furthermore, SP@RSV could significantly prolong the life span of Caenorhabditis elegans by enhancing the activity of antioxidases and without causing acute toxicity. Besides, SP@RSV-contained jelly was prepared and sensory evaluated to showcase its potential utilization in the nutraceuticals industry. These findings confirm the feasibility of using SP as a vehicle to enhance the stability, intestinal targeting and bioaccessibility of RSV.

Abstract Acidification, as an effective measure to remove blockages and restore oil well productivity, has received widespread concern. However, conventional acid systems can only be used to unblock near‐wellbore zones and are difficult to act on far‐wellbore reservoirs. In this article, scanning electron microscope, energy‐dispersive X‐ray spectroscope, and X‐ray diffractometer were used to analyze the blockages in the Bai 823 well area, and it was determined that their main components were CaCO3 and FeCO3, which provided the basis for the construction of the unblocking formula. Then, the acid dissolution experiments on the plugging materials showed that the dissolution rate of 10% HCl can reach more than 85% for the scale sample; the acid dissolution experiments on the rock sample showed that the autogenous mud acid has better dissolution performance and better retardation performance for the rock sample, and the effective action time is longer, so it can be used for deeper unplugging of the reservoir. Finally, the process parameters such as the optimal acid concentration, acid dosage, and discharge volume were optimized by establishing the fracture‐matrix acid flow reaction model. Research results indicate that the autogenous mud acid can act on the blockage in the far‐wellbore area to improve the acidification effect.

The anisotropic mechanical behavior of rocks under high-stress and high-temperature coupled conditions is crucial for analyzing the stability of surrounding rocks in deep underground engineering. This paper is devoted to studying the anisotropic strength, deformation and failure behavior of gneiss granite from the deep boreholes of a railway tunnel that suffers from high tectonic stress and ground temperature in the eastern tectonic knot in the Tibet Plateau. High-temperature true triaxial compression tests are performed on the samples using a self-developed testing device with five different loading directions and three temperature values that are representative of the geological conditions of the deep underground tunnels in the region. Effect of temperature and loading direction on the strength, elastic modulus, Poisson's ratio, and failure mode are analyzed. The method for quantitative identification of anisotropic failure is also proposed. The anisotropic mechanical behaviors of the gneiss granite are very sensitive to the changes in loading direction and temperature under true triaxial compression, and the high temperature seems to weaken the inherent anisotropy and stress-induced deformation anisotropy. The strength and deformation show obvious thermal degradation at 200 °C due to the weakening of friction between failure surfaces and the transition of the failure pattern in rock grains. In the range of 25 °C–200 °C, the failure is mainly governed by the loading direction due to the inherent anisotropy. This study is helpful to the in-depth understanding of the thermal-mechanical behavior of anisotropic rocks in deep underground projects.

Abstract The increasing number of plant mitochondrial DNA genomes (mtDNA) sequenced reveals the extent of transfer from both chloroplast DNA genomes (cpDNA) and nuclear DNA genomes (nDNA). This study created a library and assembled the chloroplast and mitochondrial genomes of the leafy sweet potato better to understand the extent of mitochondrial and chloroplast gene transfer. The full-length chloroplast genome of the leafy sweet potato (OM808940) is 161,387 bp, with 132 genes annotated, including 87 protein-coding genes, 8 rRNA genes, and 37 tRNA genes. The mitochondrial genome (OM808941) was 269,578 bp in length and contained 69 functional genes, including 39 protein-coding genes, 6 rRNA genes, and 24 tRNA genes. 68 SSR loci were found in the leafy sweet potato organelle genome, including 54 in the chloroplast genome and 14 in the mitochondria genome. In the sweet potato mitochondrial genome, most genes have RNA editing sites, and the conversion ratio from hydrophilic amino acids to hydrophobic amino acids is the highest, reaching 47.12%. Horizontal transfer occurs in the sweet potato organelle genome and nuclear genome. 40 mitochondrial genome segments share high homology with 14 chloroplast genome segments, 33 of which may be derived from chloroplast genome horizontal transfer. 171 mitochondrial genome sequences come from the horizontal transfer of nuclear genome. The phylogenetic analysis of organelle genes revealed that the leafy sweet potato was closely related to the tetraploid wild species Ipomoea tabascana and the wild diploid species Ipomoea trifida.

In this paper, a computer-vision-assisted simulation method is proposed to address the issue of training dataset acquisition for wireless hand gesture recognition. In the existing literature, in order to classify gestures via the wireless channel estimation, massive training samples should be measured in a consistent environment, consuming significant efforts. In the proposed CASTER simulator, however, the training dataset can be simulated via existing videos. Particularly, in the channel simulation, a gesture is represented by a sequence of snapshots, and the channel impulse response of each snapshot is calculated via tracing the rays scattered off a primitive-based hand model. Moreover, CASTER simulator relies on the existing video clips to extract the motion data of gestures. Thus, the massive measurements of wireless channel can be eliminated. The experiments first demonstrate an 83.0% average recognition accuracy of simulation-to-reality inference in recognizing 5 categories of gestures. Moreover, this accuracy can be boosted to 96.5% via the method of transfer learning.

Abstract Large language models (LLMs) have shown superior performance in various areas. And LLMs have the potential to revolutionize data management by serving as the "brain" of next-generation database systems. However, there are several challenges that utilize LLMs to optimize databases. First, it is challenging to provide appropriate prompts (e.g., instructions and demonstration examples) to enable LLMs to understand the database optimization problems. Second, LLMs only capture the logical database characters (e.g., SQL semantics) but are not aware of physical characters (e.g., data distributions), and it requires to fine-tune LLMs to capture both physical and logical information. Third, LLMs are not well trained for databases with strict constraints (e.g., query plan equivalence) and privacy-preserving requirements, and it is challenging to train database-specific LLMs while ensuring database privacy. To overcome these challenges, this vision paper proposes a LLM-based database framework (DB-GPT), including automatic prompt generation, DB-specific model fine-tuning, and DB-specific model design and pre-training. Preliminary experiments show that DB-GPT achieves relatively good performance in database tasks like query rewrite and index tuning. The source code and datasets are available at github.com/TsinghuaDatabaseGroup/DB-GPT.

Abstract Background The low efficiency of genetic transformation in Chinese cabbage (Brassica rapa L. ssp. pekinensis) is the key problem affecting functional verification. Particle bombardment is a widely used method along with the Agrobacterium-mediated method. As a physical means, it has almost no restrictions on the type of host and a wide range of receptor types, which largely avoids the restriction of explants. The bombardment parameters, which include the number of bombardments, the bombardment pressure, and the bombardment distance, may affect the microspores' genetic transformation efficiency. Results The transformation efficiency was improved using the particle bombardment method under the combination of bombardment shot times (3, 4, 5) × bombardment pressure (900, 1100, 1350 psi) × bombardment distance (3, 6, 9 cm). The average viability of microspores in the treatment group ranged from 74.76 to 88.55%, while the control group was 88.09%. When the number of shot times was 4, the number of embryos incubated in the treatment group ranged from 16 to 236 per dish, and the control group had 117 embryos per dish. When the bombardment parameters of the biolistic method were 4 shot times—1350 psi—3 cm, 4 times—1100 psi—3 cm, and 4 times—900 psi—3 cm, they had high transient expression efficiency, and the average number of transformed microspores was 21.67, 11.67, and 11.67 per dish (3.5 mL), respectively. When the bombardment parameters were 4 times, 900 psi, and 6 cm, the highest genetically transformed embryos were obtained, and the transformation efficiency reached 10.82%. Conclusion A new genetic transformation system with proper parameters for Chinese cabbage microspores was established using particle bombardment. This proper transformation system could provide a useful tool for the improvement of cultivar quality and the investigation of functional genes in Chinese cabbage.

With the increasing integrations of renewable energy resources into distribution networks (DNs) and microgrids (MGs), the imperative for an effective market scheduling mechanism becomes paramount to enhance the operational safety, reliability, and economic efficiency of distribution grids. Taking advantage of bi-level programming theory, this study meticulously formulates a comprehensive optimization scheduling model for the multi-MGs distribution network. The upper-level optimization objective is to minimize both the operational losses and total costs of the DN. Concurrently, the lower-level optimization pursues the maximization of daily operational revenue for MGs. Recognizing the pervasive impact of the inherent uncertainty associated with renewable energy sources on system safety and reliability, a cutting-edge scenario-based stochastic planning framework is introduced. The methodology integrates a heuristic matrix matching approach to effectively handle the intricate challenges posed by uncertainties from wind and photovoltaic generations. Moreover, in addressing the proposed nonlinear models, a sophisticated method is employed, utilizing the second-order cone relaxation and linearization methods. These methods meticulously transform the upper and lower-level models into second-order cone planning and mixed-integer linear programming issues, respectively. Finally, the proposed methodologies are rigorously scrutinized and validated with intricate case studies, providing a nuanced understanding of their efficacy. The empirical results underscore the theoretical feasibility and superiority of the proposed scheduling scheme. Notably, the operational performance of the DN as well as the economic viability of multiple MGs can also be significantly improved.

BackgroundHeavy metal exposure is an important cause of reduced bone mineral density (BMD). Epidemiological studies focusing on the effects of mixed heavy metal exposure on BMD in middle-aged and older people are scarce. In single-metal studies, men and women have shown distinct responses of BMD to environmental metal exposure. This study therefore aimed to elucidate the association between mixed heavy metal exposure and BMD and to investigate whether it is sex-specific.MethodsData from the 2017–2020 National Health and Nutrition Examination Survey were selected for this cross-sectional study. The study used three statistical methods, i.e., linear regression, Bayesian kernel machine regression (BKMR) modeling, and weighted quartiles (WQS) regression, to explore the association between the urinary concentrations of 11 metals (barium, cadmium, cobalt, cesium, manganese, molybdenum, lead, antimony, tin, thallium, and Tungsten), either individually or as a mixture, and total femoral BMD.ResultsA total of 1,031 participants were included in this study. Femoral BMD was found to be higher in men than women. A significant negative correlation between the urinary concentrations of the 10 metals and femoral BMD was found in the overall cohort. Further gender sub-stratified analyses showed that in men, urinary metal concentrations were negatively correlated with femoral BMD, with cobalt and barium playing a significant and non-linear role in this effect. In women, although urinary metal concentrations negatively modulated femoral BMD, none of the correlations was statistically significant. Antimony showed sex-specific differences in its effect.ConclusionThe urinary concentrations of 10 mixed heavy metals were negatively correlated with femoral BMD in middle-aged and older participants, and this effect showed gender differences. These findings emphasize the differing role of mixed metal exposure in the process of BMD reduction between the sexes but require further validation by prospective studies.

Gastric-type endocervical adenocarcinoma (G-EAC) represents a rare variant of cervical mucinous adenocarcinoma that is typically unrelated to human papillomavirus (HPV) infection. G-EAC exhibits highly atypical clinical presentations and characteristics, and aggressive biological behavior often leads to challenges in timely diagnosis. Here, we present a case study involving a 74-year-old Chinese woman who experienced urinary incontinence for one month. Biopsy pathology confirmed the diagnosis of G-EAC, revealing stage IVa by imaging examinations. The patient subsequently underwent three cycles of chemotherapy, followed by adjuvant radiotherapy and surgical excision of residual tumor foci. This comprehensive treatment approach yielded a favorable survival outcome. For patients with advanced G-EAC, a multimodal therapeutic approach holds promise and warrants further exploration.

Abstract The evolution due to temperature and pressure of shale reservoir permeability affects the productivity evaluation and development decision of shale gas reservoirs, which is very important for the exploration and development of unconventional gas reservoirs. This study analyzed the coupling effects of temperature (25, 50, and 75°C), effective stress (15 and 30 MPa), and pore pressure (0.5, 2.0, 4.0, and 8.0 MPa) on the permeability of the shale sample in the Longmaxi Formation. As the temperature and pressure increased, the apparent permeability exhibited a downward trend, and the absolute permeability decreased with the rise of temperature or effective stress. An in‐depth analysis of the gas slippage factors under the conditions of different temperature and pressure was conducted to evaluate the trend of the average pore width with temperature and pressure. The results were then verified by scanning electron microscopy (SEM). The results provide new insights into evaluating the permeability of the Longmaxi shale and can be used to enhance the gas recovery rate of deep shale gas reservoirs.

Changes in FOXA1 (forkhead box protein A1) protein levels are well associated with prostate cancer (PCa) progression. Unfortunately, direct targeting of FOXA1 in progressive PCa remains challenging due to variations in FOXA1 protein levels, increased FOXA1 mutations at different stages of PCa, and elusive post‐translational FOXA1 regulating mechanisms. Here, we show that SKP2 (S‐phase kinase‐associated protein 2) catalyzes K6‐ and K29‐linked polyubiquitination of FOXA1 for lysosomal‐dependent degradation. Our data indicate increased SKP2:FOXA1 protein ratios in stage IV human PCa compared to stages I–III, together with a strong inverse correlation (r = −0.9659) between SKP2 and FOXA1 levels, suggesting that SKP2–FOXA1 protein interactions play a significant role in PCa progression. Prostate tumors of Pten/Trp53 mice displayed increased Skp2–Foxa1–Pcna signaling and colocalization, whereas disruption of the Skp2–Foxa1 interplay in Pten/Trp53/Skp2 triple‐null mice demonstrated decreased Pcna levels and increased expression of Foxa1 and luminal positive cells. Treatment of xenograft mice with the SKP2 inhibitor SZL P1‐41 decreased tumor proliferation, SKP2:FOXA1 ratios, and colocalization. Thus, our results highlight the significance of the SKP2–FOXA1 interplay on the luminal lineage in PCa and the potential of therapeutically targeting FOXA1 through SKP2 to improve PCa control.

This study examined the thermal reflective properties of composite inorganic coatings applied to various wall types. It evaluated the influence of these coatings on the thermal insulation and reflectivity of the walls. The findings indicate that coating application markedly enhances a wall’s thermal insulation capabilities and increases its heat flux reflection ratio. These results offer crucial theoretical backing and practical guidance for the future use of coating technologies in construction. By refining the coating formulations and application processes, the thermal insulation properties of walls can be further enhanced, thus making a significant contribution to building energy efficiency and environmental protection. Consequently, this research provides essential references and insights for advancing coating technology in the construction industry.

Abstract Antimicrobial resistance (AMR) from pathogenic bacterial biofilms has become a global health issue while developing novel antimicrobials is inefficient and costly. Combining existing multiple drugs with enhanced efficacy and/or reduced toxicity may be a promising approach to treat AMR. D‐amino acids mixtures coupled with antibiotics can provide new therapies for drug‐resistance infection with reduced toxicity by lower drug dosage requirements. However, iterative trial‐and‐error experiments are not tenable to prioritize credible drug formulations, owing to the extremely large number of possible combinations. Herein, a new avenue is provide to accelerate the exploration of desirable antimicrobial formulations via high‐throughput screening and machine learning optimization. Such an intelligent method can navigate the large search space and rapidly identify the D‐amino acid mixtures with the highest anti‐biofilm efficiency and also the synergisms between D‐amino acid mixtures and antibiotics. The optimized drug cocktails exhibit high antimicrobial efficacy while remaining non‐toxic, which is demonstrated not only from in vitro assessments but also the first in vivo study using a lung infection mouse model.

Summary: Enhancers of polycomb 1 (EPC1) and 2 (EPC2) are involved in multiple biological processes as components of histone acetyltransferases/deacetylase complexes and transcriptional cofactors, and their dysfunction was associated with developmental defects and diseases. However, it remains unknown how their dysfunction induces hematopoietic stem and progenitor cell (HSPC) defects. Here, we show that depletion of EPC1/2 significantly reduced the number of hematopoietic stem and progenitor cells (HSPCs) in the aorta-gonad mesonephros and caudal hematopoietic tissue regions by impairing HSPC proliferation, and consistently downregulated the expression of HSPC genes in K562 cells. This study demonstrates the functions of EPC1/2 in regulating histone H3 acetylation, and in regulating DLST (dihydrolipoamide S-succinyltransferase) via H3 acetylation and cooperating with transcription factors serum response factor and FOXR2 together, and in the subsequent HSPC emergence and proliferation. Our results demonstrate the essential roles of EPC1/2 in regulating H3 acetylation, and DLST as a linkage between EPC1 and EPC2 with mitochondria metabolism, in HSPC emergence and proliferation.

IntroductionRevealing factors and mechanisms in determining species co-existence are crucial to community ecology, but studies using gut microbiota data are still lacking.MethodsUsing gut microbiota data of 556 Brandt’s voles from 37 treatments in eight experiments, we examined the relationship of species co-occurrence of gut microbiota in Brandt’s voles (Lasiopodomys brandtii) with genetic distance (or genetic relatedness), community diversity, and several environmental variables.ResultsWe found that the species co-occurrence index (a larger index indicates a higher co-occurrence probability) of gut microbiota in Brandt’s voles was negatively associated with the genetic distance between paired ASVs and the number of cohabitating voles in the experimental space (a larger number represents more crowding social stress), but positively with Shannon diversity index, grass diets (representing natural foods), and non-physical contact within an experimental space (representing less stress).DiscussionOur study demonstrated that high diversity, close genetic relatedness, and favorable living conditions would benefit species co-occurrence of gut microbiota in hosts. Our results provide novel insights into factors and mechanisms that shape the community structure and function of gut microbiota and highlight the significance of preserving the biodiversity of gut microbiota.

BackgroundOccupational exposure to lead, cadmium, or arsenic is a potential risk factor for blood pressure elevation. Current studies mainly focus on the relationship between a single metal and blood pressure. However, mixed metal exposure often exists in the actual working environment, and the interactive effects of polymetallic interactions on blood pressure and the dose-effect relationship remain unclear yet. ObjectiveTo explore the influence proportion of occupational exposure to lead, cadmium, or arsenic on blood pressure and their interactive effects. MethodsFrom January to December 2021, workers from a smelter in southern China were selected. Demographic characteristics, height, weight, and blood pressure of workers were collected through questionnaire and physical examination. At the same time, their urine samples were collected and the levels of urinary lead, urinary cadmium, and urinary arsenic were detected by inductively coupled plasma mass spectrometry, and corrected by urinary creatinine (Cr). Linear regression and logistic regression were used to analyze the relationship between urinary lead, cadmium, and arsenic and blood pressure. Weighted quantile sum (WQS) regression was applied to evaluate the dose-effect relationship between urinary lead, cadmium, and arsenic exposures and blood pressure and the effect weight of each metal on blood pressure. Generalized linear regression and additive/multiplicative scaling were used to identify interactive effects of the three metals on blood pressure. ResultsA total of 1075 workers were included in this study, with a mean age of (44.68±5.11) years and mean working seniority of (24.66±5.23) years. There were 891 males (88.9%) and 184 were females (17.1%); 24.7% workers were drinkers and 45.7% workers were smokers; 302 workers (28.1%) reported hypertension and 37 of them were taking antihypertensive drugs. The P50 (P25, P75) levels of urinary lead, urinary cadmium, and urinary arsenic were 6.11 (3.71, 11.08), 3.88 (2.68, 5.44), and 26.04 (19.99, 35.11) μg·g−1, respectively. After adjusting for gender, age, working seniority, body mass index, smoking, drinking, and the usage of antihypertensive drugs, systolic and diastolic blood pressure increased by 0.772 and 0.418 mmHg respectively for 10% increase in lead, cadmium, and arsenic mixed exposure. Urinary cadmium, among the three single exposures, had the greatest effect on systolic and diastolic blood pressure, weight (w)=0.523 and 0.551 respectively. The interaction of urinary lead and urinary cadmium was positively correlated with the occurrence of hypertension, multiplicative interaction OR (ORint)=1.88 (95%CI: 1.09, 3.63), attributable proportion due to interaction (AP)=1.19 (95%CI: 0.40, 8.18). ConclusionThis study shows that mixed exposure to lead, cadmium, and arsenic has a positive relationship with blood pressure, in which cadmium plays a major role. Co-exposure to lead and cadmium has a positive interactive effect on hypertension development and systolic blood pressure elevation.

Abstract Background Although spatial organization of compartments and topologically associating domains at large scale is relatively well studied, the spatial organization of regulatory elements at fine scale is poorly understood in plants. Results Here we perform high-resolution chromatin interaction analysis using paired-end tag sequencing approach. We map chromatin interactions tethered with RNA polymerase II and associated with heterochromatic, transcriptionally active, and Polycomb-repressive histone modifications in Arabidopsis. Analysis of the regulatory repertoire shows that distal active cis-regulatory elements are linked to their target genes through long-range chromatin interactions with increased expression of the target genes, while poised cis-regulatory elements are linked to their target genes through long-range chromatin interactions with depressed expression of the target genes. Furthermore, we demonstrate that transcription factor MYC2 is critical for chromatin spatial organization, and propose that MYC2 occupancy and MYC2-mediated chromatin interactions coordinately facilitate transcription within the framework of 3D chromatin architecture. Analysis of functionally related gene-defined chromatin connectivity networks reveals that genes implicated in flowering-time control are functionally compartmentalized into separate subdomains via their spatial activity in the leaf or shoot apical meristem, linking active mark- or Polycomb-repressive mark-associated chromatin conformation to coordinated gene expression. Conclusion The results reveal that the regulation of gene transcription in Arabidopsis is not only by linear juxtaposition, but also by long-range chromatin interactions. Our study uncovers the fine scale genome organization of Arabidopsis and the potential roles of such organization in orchestrating transcription and development.

This article addresses several sharp weighted Adams type inequalities in Lorentz-Sobolev spaces by using symmetry, rearrangement and the Riesz representation formula. In particular, the sharpness of these inequalities were also obtained by constructing a proper test sequence.

Raman spectroscopy for rapid identification of foodborne pathogens based on phenotype has attracted increasing attention, and the reliability of the Raman fingerprint database through genotypic determination is crucial. In the research, the classification model of four foodborne pathogens was established based on t-distributed stochastic neighbor embedding (t-SNE) and support vector machine (SVM); the recognition accuracy was 97.04%. The target bacteria named by the model were ejected through Raman-activated cell ejection (RACE), and then single-cell genomic DNA was amplified for species analysis. The accuracy of correct matches between the predicted phenotype and the actual genotype of the target cells was at least 83.3%. Furthermore, all anticipant sequencing results brought into correspondence with the species were predicted through the model. In sum, the Raman fingerprint database based on Raman spectroscopy combined with machine learning was reliable and promising in the field of rapid detection of foodborne pathogens.

Current challenges in visible and infrared image fusion include color information distortion, texture detail loss, and target edge blur. To address these issues, a fusion algorithm based on double-domain transform filter and nonlinear contrast transform feature extraction (DDCTFuse) is proposed. First, for the problem of incomplete detail extraction that exists in the traditional transform domain image decomposition, an adaptive high-pass filter is proposed to decompose images into high-frequency and low-frequency portions. Second, in order to address the issue of fuzzy fusion target caused by contrast loss during the fusion process, a novel feature extraction algorithm is devised based on a novel nonlinear transform function. Finally, the fusion results are optimized and color-corrected by our proposed spatial-domain logical filter, in order to solve the color loss and edge blur generated in the fusion process. To validate the benefits of the proposed algorithm, nine classical algorithms are compared on the LLVIP, MSRS, INO, and Roadscene datasets. The results of these experiments indicate that the proposed fusion algorithm exhibits distinct targets, provides comprehensive scene information, and offers significant image contrast.

Studies on the lung cancer genome are indispensable for developing a cure for lung cancer. Whole-genome resequencing, genome-wide association studies, and transcriptome sequencing have greatly improved our understanding of the cancer genome. However, dysregulation of long-range chromatin interactions in lung cancer remains poorly described. To better understand the three-dimensional (3D) genomic interaction features of the lung cancer genome, we used the A549 cell line as a model system and generated high-resolution chromatin interactions associated with RNA polymerase II (RNAPII), CCCTC-binding factor (CTCF), enhancer of zeste homolog 2 (EZH2), and histone 3 lysine 27 trimethylation (H3K27me3) using long-read chromatin interaction analysis by paired-end tag sequencing (ChIA-PET). Analysis showed that EZH2/H3K27me3-mediated interactions further repressed target genes, either through loops or domains, and their distributions along the genome were distinct from and complementary to those associated with RNAPII. Cancer-related genes were highly enriched with chromatin interactions, and chromatin interactions specific to the A549 cell line were associated with oncogenes and tumor suppressor genes, such as additional repressive interactions on FOXO4 and promoter–promoter interactions between NF1 and RNF135. Knockout of an anchor associated with chromatin interactions reversed the dysregulation of cancer-related genes, suggesting that chromatin interactions are essential for proper expression of lung cancer-related genes. These findings demonstrate the 3D landscape and gene regulatory relationships of the lung cancer genome.

Macrocystis pyrifera is a large perennial brown alga used as a raw material in the chemical, energy, and medicine industries. It is also a high-quality material for the construction of seaweed beds with extremely high economic and ecological value. In the 1980s, M. pyrifera was introduced to China, and many experiments on its seedling and cultivation technologies were undertaken. However, research on its ecological adaptability is relatively challenging, and the aquaculture industry has not yet developed due to bottleneck problems. In the present study, the MaxEnt model was used to predict the suitability and potential invasion risk of M. pyrifera in China to lay a foundation for M. pyrifera culture industry development and marine ecological construction. Parameter optimization showed that the predictive performance of the model was the best when the feature combination was product, quadratic, and hinge features and the regularization multiplier was 0.8. Considering the correlation between environmental attributes and their contribution to the model, six environmental factors were selected to construct a prediction model for the suitability of M. pyrifera. Among these, light intensity and temperature produced the greatest impact on the natural distribution of M. pyrifera. For high suitable growth probability, the optimal light intensity was > 2 μmol/(m2·s) and the optimum temperature range was 10.5~17℃. Combined with ArcGIS, the modeling results showed that the suitable habitats for M. pyrifera in China are mainly distributed in the Yellow Sea and Bohai Sea, accounting for approximately 13.17% of the sea area, with a marginal suitability of 5.46%, low suitability of 2.85%, moderate suitability of 1.20%, and high suitability of 3.66%. Furthermore, Liaodong Bay and Bohai Bay are suitable sea areas for the introduction and cultivation of M. pyrifera as well as the construction of M. pyrifera farms. Some areas in Liaodong Bay are highly suitable, indicating a certain risk of invasion. Therefore, ecological safety evaluations should be strengthened if M. pyrifera cultivation is promoted near this area.

Abstract Background While immune checkpoint inhibitors (ICIs) are associated with elevated cardiovascular risks, evidence of any association between ICIs and myocardial infarction (MI) was scarce, especially in Asians. Methods Using prospectively collected population‐based data, this self‐controlled case series included patients prescribed an ICI between 1/1/2014 and 31/12/2020 in Hong Kong who had MI within January 1, 2013 to December 31, 2021. Incidence rate ratios (IRRs) for MI during and after ICI exposure were estimated, compared to the year before ICI initiation. Results Of 3684 identified ICI users, 24 had MI during the study period. MI incidence increased significantly in the first 90 days of exposure (IRR 3.59 [95% confidence interval: 1.31–9.83], p = 0.013), but not days 91–180 (p = 0.148) or ≥181 (p = 0.591) of exposure, nor postexposure (p = 0.923). Sensitivity analyses excluding patients with MI‐related death and incorporating extended exposure periods produced consistent results separately. Conclusions ICIs were associated with increased MI incidence in Asian Chinese patients during the first 90 days of use, but not later.

A nitrate transporter gene, named B46NRT2.1, from salt-tolerant Zea mays L. B46 has been cloned. B46NRT2.1 contained the same domain belonging to the major facilitator superfamily (PLN00028). The results of the phylogenetic tree indicated that B46NRT2.1 exhibits sequence similarity and the closest relationship with those known nitrate transporters of the NRT2 family. Through RT-qPCR, we found that the expression of B46NRT2.1 mainly happens in the root and leaf. Moreover, the treatment with NaCl, Na2CO3, and NaHCO3 could significantly increase the expression of B46NRT2.1. B46NRT2.1 was located in the plasma membrane. Through the study of yeast and plant salt response brought by B46NRT2.1 overexpression, we have preliminary knowledge that the expression of B46NRT2.1 makes yeast and plants respond to salt shock. There are 10 different kinds of cis-acting regulatory elements (CRES) in the promotor sequences of B46NRT2.1 gene using the PlantCARE web server to analyze. It mainly includes hormone response, abscisic acid, salicylic acid, gibberellin, methyl jasmonate, and auxin. The B46NRT2.1 gene’s co-expression network showed that it was co-expressed with a number of other genes in several biological pathways, including regulation of NO3 long-distance transit, modulation of nitrate sensing and metabolism, nitrate assimilation, and transduction of Jasmonic acid-independent wound signal. The results of this work should serve as a good scientific foundation for further research on the functions of the NRT2 gene family in plants (inbred line B46), and this research adds to our understanding of the molecular mechanisms under salt tolerance.

In order to further improve the efficiency of energy utilization, Integrated Energy Systems (IES) connect various energy systems closer, which has become an important energy utilization mode in the process of energy transition. Because the complex and variable multiple load is an important part of the new power system, the load forecasting is of great significance for the planning, operation, control, and dispatching of the new power system. In order to timely track the latest research progress of the load forecasting method and grasp the current research hotspot and the direction of load forecasting, this paper reviews the relevant research content of the forecasting methods. Firstly, a brief overview of Integrated Energy Systems and load forecasting is provided. Secondly, traditional forecasting methods based on statistical analysis and intelligent forecasting methods based on machine learning are discussed in two directions to analyze the advantages, disadvantages, and applicability of different methods. Then, the results of Integrated Energy Systemss multiple load forecasting for the past 5 years are compiled and analyzed. Finally, the Integrated Energy Systems load forecasting is summarized and looked forward.

Summary: Background: Cervical squamous cell carcinoma (CSCC) and adenocarcinoma (CAde) are two major pathological types of cervical cancer (CC), but their high-resolution heterogeneity of tumor and immune microenvironment remains elusive. Methods: Here, we performed single-nucleus RNA sequencing (snRNA-seq) from five CSCC and three CAde samples, and systematically outlined their specific transcriptome atlas. Findings: We found CD8+ T cells in CSCC were more cytotoxic but lower exhausted compared to those in CAde, and phagocytic MRC1+ macrophages were specifically enriched in CSCC. Interestingly, we discovered that pro-tumoral cancer-associated myofibroblasts (myoCAFs) and cancer-associated vascular-fibroblasts (vCAFs) were more abundant in CSCC, and further verified their pro-metastatic roles in vitro. Furthermore, we also identified some specific chemotherapy drugs for CSCC (Dasatinib and Doramapimod) and CAde (Pyrimethamine and Lapatinib) by revealing their heterogeneity in transcriptomic profiles of malignant epithelial cells, and further verified their specific sensitivity in cell lines and constructed CC-derived organoids. Cell–cell communication networks revealed that the pathways of NRG1-ERBB2, and FN1-ITAG3 were specific for CAde and CSCC, respectively, which may partly explain the specificities of identified chemotherapy drugs. Interpretation: Our study described the immune heterogeneity and specific cellular interactions between CSCC and CAde, which could provide insights for uncovering pathogenesis and designing personalized treatment. Fundings: National Key R&D Program of China (2021YFC2701201), National Natural Science Foundation of China (82072895, 82141106, 82103134, 81903114).

This study aimed to understand the community successions driven by different starters and their effects on the flavor development of Chinese fermented sausages. The results showed that the bacterial genus (67.6%) and pH (32.4%) were the key factors influencing the volatile profile. Inoculated the starters composed of Pediococcus and staphylococci maintained the stable community succession patterns dominated by staphylococci (samples T and S). Although the highly acidic environment (pH 5.4) resulted in a stable succession pattern of the microbial community, and it was not conducive to the accumulation of aldehydes, alcohols and esters.

Abstract The ongoing coronavirus disease 2019 (COVID‐19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has caused great public health concern and has been a global threat due to its high transmissibility and morbidity. Although the SARS‐CoV‐2 transmission mainly relies on the person‐to‐person route through the respiratory droplets, the possible transmission through the contaminated cold‐chain food and packaging to humans has raised widespread concerns. This review discussed the possibility of SARS‐CoV‐2 transmission via the contaminated cold‐chain food and packaging by tracing the occurrence, the survival of SARS‐CoV‐2 in the contaminated cold‐chain food and packaging, as well as the transmission and outbreaks related to the contaminated cold‐chain food and packaging. Rapid, accurate, and reliable diagnostics of SARS‐CoV‐2 is of great importance for preventing and controlling the COVID‐19 resurgence. Therefore, we summarized the recent advances on the emerging clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system‐based biosensing technology that is promising and powerful for preventing the possible COVID‐19 resurgence caused by the contaminated cold‐chain food and packaging during the COVID‐19 pandemic, including CRISPR/Cas system‐based biosensors and their integration with portable devices (e.g., smartphone, lateral flow assays, microfluidic chips, and nanopores). Impressively, this review not only provided an insight on the possibility of SARS‐CoV‐2 transmission through the food supply chain, but also proposed the future opportunities and challenges on the development of CRISPR/Cas system‐based detection methods for the diagnosis of SARS‐CoV‐2.

Temperature is an important environmental factor affecting streamer discharge. However, the mechanism and regularity of the influence are still unclear. This paper analyzes the mechanism of how the parameters in the hydrodynamic model are affected by temperature and the finite element method is used to solve three particle continuity equations along with Poisson’s equation simultaneously. The results show that the increase in temperature inhibits the ionization and the attachment process, and the reduction rate of the ionization coefficient is 40 times the attachment coefficient numerically, which means that the streamer is easier to initiate at low temperatures. The increase in temperature accelerates the diffusion and drift of electrons. This effect increases the average velocity of the streamer, and the average velocity increases by about 4.89m/( $\text{s}\cdot \text{K}$ ) with temperature, which means that the fast-moving charged particles at high temperature may affect the discharge signals. The essence of the influence of temperature on the physical quntities in the streamer discharge is its influence on ionization, attachment, diffusion, and drift effects. The results in this paper can comprehensively consider the effects and obtain the effect mechanism of temperature on the micro-process of the streamer, contributing to the research on the insulation design of power equipment and the influence of temperature on the discharge signals.

The purple-leaf phenotype in pak choi is due to the accumulation of anthocyanin. The main regulated genes are unclear. The gene controlling the purple-leaf phenotype was mapped on A03 using BSA-seq, but the candidate interval was not further narrowed with InDel markers. Based on our previous study, we hypothesized that the candidate gene that regulates purple leaves in pak choi may also be the Dark_Pur gene from B. juncea. Using the Dark_Pur-1 marker to identify P1, P2, F1, and F2, it was confirmed that the purple trait in purple-leaf pak choi was controlled by the Dark_Pur gene from B. juncea through distant hybridization. A DNA segment of approximately 514 Kb containing the Dark_Pur gene was reintroduced into pak choi from B. juncea. Meanwhile, a new purple pak choi germplasm line was created with green pak choi × purple B. juncea via distant hybridization, which proved that distant hybridization is an effective method for creating new germplasms. Furthermore, the purple-leaf phenotypes of 20 pak choi varieties were identified, and the purple-leaf traits of all lines were derived from B. juncea via distant hybridization. At present, few studies have focused on the background of the purple trait in pak choi; however, in this study, our results suggest that there is a high probability that the purple trait in pak choi may be completely derived from purple B. juncea via distant hybridization. This study also lays a good foundation for research on the creation of new germplasms through distant hybridization among the Brassica species.

The soil-borne pathogen Plasmodiophora brassicae is the causal agent of clubroot, a major disease in Chinese cabbage (Brassica rapa ssp. pekinensis). The host’s resistance genes often confer immunity to only specific pathotypes and may be rapidly overcome. Identification of novel clubroot resistance (CR) from germplasm sources is necessary. In this study, Bap246 was tested by being crossed with different highly susceptible B. rapa materials and showed recessive resistance to clubroot. An F2 population derived from Bap246 × Bac1344 was used to locate the resistance Quantitative Trait Loci (QTL) by Bulk Segregant Analysis Sequencing (BSA-Seq) and QTL mapping methods. Two QTL on chromosomes A01 (4.67–6.06 Mb) and A08 (10.42–11.43 Mb) were found and named Cr4Ba1.1 and Cr4Ba8.1, respectively. Fifteen and eleven SNP/InDel markers were used to narrow the target regions in the larger F2 population to 4.67–5.17 Mb (A01) and 10.70–10.84 Mb (A08), with 85 and 19 candidate genes, respectively. The phenotypic variation explained (PVE) of the two QTL were 30.97% and 8.65%, respectively. Combined with gene annotation, mutation site analysis, and real-time quantitative polymerase chain reaction (qRT-PCR) analysis, one candidate gene in A08 was identified, namely Bra020861. And an insertion and deletion (InDel) marker (co-segregated) named Crr1-196 was developed based on the gene sequence. Bra013275, Bra013299, Bra013336, Bra013339, Bra013341, and Bra013357 in A01 were the candidate genes that may confer clubroot resistance in Chinese cabbage. The resistance resource and the developed marker will be helpful in Brassica breeding programs.

Vernalization plays a crucial role in the flowering and yield of Chinese cabbage, a process intricately influenced by long non-coding RNAs (lncRNAs). Our research focused on lncFLC1, lncFLC2a, and lncFLC2b, which emerged as key players in this process. These lncRNAs exhibited an inverse expression pattern to the flowering repressor genes FLOWERING LOCUS C 1 (BrFLC1) and FLOWERING LOCUS C 2 (BrFLC2) during vernalization, suggesting a complex regulatory mechanism. Notably, their expression in the shoot apex and leaves was confirmed through in fluorescent in situ hybridization (FISH). Furthermore, when these lncRNAs were overexpressed in Arabidopsis, a noticeable acceleration in flowering was observed, unveiling functional similarities to Arabidopsis’s COLD ASSISTED INTRONIC NONCODING RNA (COOLAIR). This resemblance suggests a potentially conserved regulatory mechanism across species. This study not only enhances our understanding of lncRNAs in flowering regulation, but also opens up new possibilities for their application in agricultural practices.

Strong gravitational lensing is a powerful tool for investigating dark matter and dark energy properties. With the advent of large-scale sky surveys, we can discover strong-lensing systems on an unprecedented scale, which requires efficient tools to extract them from billions of astronomical objects. The existing mainstream lens-finding tools are based on machine-learning algorithms and applied to cutout-centered galaxies. However, according to the design and survey strategy of optical surveys by the China Space Station Telescope (CSST), preparing cutouts with multiple bands requires considerable efforts. To overcome these challenges, we have developed a framework based on a hierarchical visual transformer with a sliding window technique to search for strong-lensing systems within entire images. Moreover, given that multicolor images of strong-lensing systems can provide insights into their physical characteristics, our framework is specifically crafted to identify strong-lensing systems in images with any number of channels. As evaluated using CSST mock data based on a semianalytic model named CosmoDC2, our framework achieves precision and recall rates of 0.98 and 0.90, respectively. To evaluate the effectiveness of our method in real observations, we have applied it to a subset of images from the DESI Legacy Imaging Surveys and media images from Euclid Early Release Observations. A total of 61 new strong-lensing system candidates are discovered by our method. However, we also identified false positives arising primarily from the simplified galaxy morphology assumptions within the simulation. This underscores the practical limitations of our approach while simultaneously highlighting potential avenues for future improvements.

Drought stress can seriously affect the yield and quality of wheat (Triticum aestivum). So far, although few wheat heat shock transcription factors (Hsfs) have been found to be involved in the stress response, the biological functions of them, especially the members of the HsfC (heat shock transcription factor C) subclass, remain largely unknown. Here, we identified a class C encoding gene, TaHsfC3-4, based on our previous omics data and analyzed its biological function in transgenic plants. TaHsfC3-4 encodes a protein containing 274 amino acids and shows the basic characteristics of the HsfC class. Gene expression profiles revealed that TaHsfC3-4 was constitutively expressed in many tissues of wheat and was induced during seed maturation. TaHsfC3-4 could be upregulated by PEG and abscisic acid (ABA), suggesting that this Hsf may be involved in the regulation pathway depending on ABA in drought resistance. Further results represented that TaHsfC3-4 was localized in the nucleus but had no transcriptional activation activity. Notably, overexpression of TaHsfC3-4 in Arabidopsis thaliana pyr1pyl1pyl2pyl4 (pyr1pyl124) quadruple mutant plants complemented the ABA-hyposensitive phenotypes of the quadruple mutant including cotyledon greening, root elongation, seedling growth, and increased tolerance to drought, indicating positive roles of TaHsfC3-4 in the ABA signaling pathway and drought tolerance. Furthermore, we identified TaHsfA2-11 as a TaHsfC3-4-interacting protein by yeast two-hybrid (Y2H) screening. The experimental data show that TaHsfC3-4 can indeed interact with TaHsfA2-11 in vitro and in vivo. Moreover, transgenic Arabidopsis TaHsfA2-11 overexpression lines exhibited enhanced drought tolerance, too. In summary, our study confirmed the role of TaHsfC3-4 in response to drought stress and provided a target locus for marker-assisted selection breeding to improve drought tolerance in wheat.

Maize is one of the major crops that has demonstrated success in the utilization of heterosis. Developing high-yield hybrids is a crucial part of plant breeding to secure global food demand. In this study, we conducted a genome-wide association study (GWAS) for 10 agronomic traits using a typical breeder population comprised 442 single-cross hybrids by evaluating additive, dominance, and epistatic effects. A total of 49 significant single nucleotide polymorphisms (SNPs) and 69 significant pairs of epistasis were identified, explaining 26.2% to 64.3% of the phenotypic variation across the 10 traits. The enrichment of favorable genotypes is significantly correlated to the corresponding phenotype. In the confident region of the associated site, 532 protein-coding genes were discovered. Among these genes, the Zm00001d044211 candidate gene was found to negatively regulate starch synthesis and potentially impact yield. This typical breeding population provided a valuable resource for dissecting the genetic architecture of yield-related traits. We proposed a novel mating strategy to increase the GWAS efficiency without utilizing more resources. Finally, we analyzed the enrichment of favorable alleles in the Shaan A and Shaan B groups, as well as in each inbred line. Our breeding practice led to consistent results. Not only does this study demonstrate the feasibility of GWAS in F1 hybrid populations, it also provides a valuable basis for further molecular biology and breeding research.

The James Webb Space Telescope (JWST) marks a new era of astronomical observation and discovery, providing unrivaled precision in various measurements, including photometry, morphology, and shear measurement. Accurate point-spread function (PSF) models are essential for many of these measurements. In this paper, we introduce HybPSF, a hybrid PSF construction method for JWST NIRCam imaging data that combines the WebbPSF software, which simulates the PSF for JWST, with observed data to produce more accurate and reliable PSF models. We apply this method to the SMACS J0723 imaging data and construct supplementary structures from residuals obtained by subtracting the WebbPSF PSF model from the data. Our results show that HybPSF significantly reduces discrepancies between the PSF model and the data compared to WebbPSF. Specifically, the PSF shape parameter ellipticity and size comparisons indicate that HybPSF improves precision by approximately 10 times for R ^2 and 50% for e . This improvement has important implications for astronomical measurements using JWST NIRCam imaging data.

Abstract Lung cancer is the leading cause of cancer‐related deaths worldwide. DNA methylation has been recognized as a potential biomarker for lung cancer diagnosis. Most reported DNA methylation biomarkers focus on promoter regions, leaving enhancer regions largely unexplored. Here, we employed multiomics data to identify DNA methylation biomarkers for non‐small‐cell lung cancer diagnosis. Especially, we linked enhancers to their target genes using long‐range chromatin interactions for biomarker prediction. We discovered two sets of DNA methylation biomarkers: one in promoter regions and another in enhancer regions. Both achieved extremely high sensitivity and specificity in five independent validation data sets. Compared with three other reported biomarker sets, both groups in our study demonstrated better and more robust classification performance in validation data sets. These novel DNA methylation biomarkers may improve lung cancer screening and ultimately contribute to improved clinical outcomes for patients. To our best knowledge, this is the first time to introduce chromatin interactions to link enhancers to their targets for biomarker study, highlighting the potential of enhancer methylation as a complement to current promoter‐based DNA methylation biomarkers. Our approach may have potential applications for other cancer types and could be a valuable direction for future research in the field of cancer biomarker discovery.

Abstract Atrial cardiomyopathy refers to structural and electrical remodelling of the atria, which can lead to impaired mechanical function. While historical studies have implicated atrial fibrillation as the leading cause of cardioembolic stroke, atrial cardiomyopathy may be an important, underestimated contributor. To date, the relationship between atrial cardiomyopathy, atrial fibrillation, and cardioembolic stroke remains obscure. This review summarizes the pathogenesis of atrial cardiomyopathy, with a special focus on neurohormonal and inflammatory mechanisms, as well as the role of adipose tissue, especially epicardial fat in atrial remodelling. It reviews the current evidence implicating atrial cardiomyopathy as a cause of embolic stroke, with atrial fibrillation as a lagging marker of an increased thrombogenic atrial substrate. Finally, it discusses the potential of antithrombotic therapy in embolic stroke with undetermined source and appraises the available diagnostic techniques for atrial cardiomyopathy, including imaging techniques such as echocardiography, computed tomography, and magnetic resonance imaging as well as electroanatomic mapping, electrocardiogram, biomarkers, and genetic testing. More prospective studies are needed to define the relationship between atrial cardiomyopathy, atrial fibrillation, and embolic stroke and to establish a prompt diagnosis and specific treatment strategies in these patients with atrial cardiomyopathy for the secondary and even primary prevention of embolic stroke.

Background and aims: Adventitial remodeling is an important pathological process of atherosclerosis, but cues implicated in adventitial remodeling are far from fully understood. Periostin (POSTN), a matricellular protein, has been demonstrated to have multiple roles in cardiovascular diseases. The aim of the study was to explore the function of POSTN in adventitial remodeling during atherosclerosis. Methods: An atherosclerosis model was constructed based on ApoE-/- mice fed a high-fat and high-cholesterol diet. The expression of POSTN in the adventitia of mouse atherosclerotic vascular specimens was detected by immunohistochemical staining. The roles of POSTN in regulating adventitial fibroblast activation were assessed by cell contractility and activation marker α-smooth muscle actin (α-SMA) expression evaluation in adventitial fibroblasts overexpressing POSTN. In addition, we performed quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting to examine the expression of the proinflammatory chemokines transforming growth factor-β1 (TGF-β1) and monocyte chemotactic protein 1 (MCP1), as well as some extracellular matrix (ECM)-related proteins, in POSTN-overexpressing adventitial fibroblasts. Finally, the integrin-related signaling pathway was detected upon POSTN overexpression in adventitial fibroblasts. Results: POSTN was highly expressed in the adventitia of atherosclerotic aortae in the mouse atherosclerosis model and promoted the activation and contraction of adventitial fibroblasts. Meanwhile, POSTN also induced adventitial fibroblasts to express TGF-β1, monocyte chemotactic protein-1 (MCP1), and ECM-related proteins and activated the phosphorylation of focal adhesion kinase (FAK) and Src. Conclusions: Our results revealed that POSTN is elevated in adventitia during atherosclerosis and contributes to the adventitial remodeling of atherosclerosis by activating adventitial fibroblasts.

Abstract Background Quantum nanodots especially carbon nanoparticles (CNPs) have been widely studied in biomedicine in imaging, and drug delivery, but anti-cancer mechanisms remain elusive. Methods Here, we investigated a type of cell death induced by food (beet, soybean) derived CNPs in cancer cells and tested whether CNPs induced DNA damage and resistant to anti-cancer agent PARP inhibitor (PARPi) could be overcome by quantum calculations, TEM, AFM, FT-IR, soft agar assay, and cytotoxicity assay. Results At high doses, CNPs derived from beet lead to a pop-like apoptosis (Carbopoptosis) in cancer cells. Quantum mechanical calculations confirmed CNPs binding with phosphate groups as well as DNA bases. At low doses, CNPs develop PARPi drug resistance through interactions between CNPs and PARPi. A synergistic drug effect was achieved with the combination of phosphatase inhibitor (PPi), PARPi, and CNPs. This is corroborated by the fact that sulfur modulated CNPs which exhibit super high phosphatase nanozyme activity abrogated the CNPs induced colony formation in anchorage-independent cancer cell growth. Conclusion Thus, our data suggest the CNPs intrinsic nanozyme activity of phosphatase may crosstalk with drug resistance, which can be reversed upon modulations.

Abstract Background Seasonal breeding in mammals has been widely recognized to be regulated by photoperiod, but the association of gut microbiota with photoperiodic regulation of seasonal breeding has never been investigated. Results In this study, we investigated the association of gut microbiota with photoperiod-induced reproduction in male Brandt’s voles (Lasiopodomys brandtii) through a long-day and short-day photoperiod manipulation experiment and fecal microbiota transplantation (FMT) experiment. We found photoperiod significantly altered reproductive hormone and gene expression levels, and gut microbiota of voles. Specific gut microbes were significantly associated with the reproductive hormones and genes of voles during photoperiod acclimation. Transplantation of gut microbes into recipient voles induced similar changes in three hormones (melatonin, follicle-stimulating hormone, and luteinizing hormone) and three genes (hypothalamic Kiss-1, testicular Dio3, and Dio2/Dio3 ratio) to those in long-day and short-day photoperiod donor voles and altered circadian rhythm peaks of recipient voles. Conclusions Our study firstly revealed the association of gut microbiota with photoperiodic regulation of seasonal breeding through the HPG axis, melatonin, and Kisspeptin/GPR54 system. Our results may have significant implications for pest control, livestock animal breeding, and human health management. Video Abstract

Here the authors delineate the dynamic changes in 3D genome and epigenome of differentiating macrophages and during infection with Mycobacterium tuberculosis. They reveal a role for NF-κB upon infection and identify SNPs in disease-susceptible loci, including rs1873613 that is located in the anchor of a dynamic chromatin loop.

Abstract Background The combination of oncolytic viruses (OVs) with immune checkpoint blockades is a research hotspot and has shown good efficacy. Here, we present the first attempt to combine oncolytic herpes simplex virus 2 (OH2) with an anti-SIRPα antibody as an antitumour treatment. Our results provide unique insight into the combination of innate immunity with OV. Methods We verified the polarization and activation of OH2 in RAW264.7 cells in vitro. Subsequently, we evaluated the antitumour ability of OH2 and anti-SIRPα combined therapy in a tumour-bearing mouse model. RNA-seq and Single-cell RNA-seq were used to characterize the changes in the tumour microenvironment. Results The OH2 lysates effectively stimulated RAW264.7 cells to polarize towards the M1 but not the M2 phenotype and activated the function of the M1 phenotype in vitro. In the macrophage clearance experiment, OH2 therapy induced polarization of M1 macrophages and participated in the antitumour immune response in a tumour-bearing mouse model. Treatment with a combination of OH2 and anti-SIRPα effectively inhibited tumour growth and significantly prolonged the survival time of the mice, and this result was more obvious in the mouse model with a larger tumour volume at the beginning of the treatment. These results suggest that combination therapy can more profoundly reshape the TME and activate stronger innate and adaptive immune responses. Conclusions Our data support the feasibility of oncolytic virus therapy in combination with anti-SIRPα antibodies and suggest a new strategy for oncolytic virus therapy.

Abstract Background It is challenging to determine the effect of DNA methylation on the epigenetic landscape and the function in higher organisms due to the lack of DNA methylation-free mutants. Results Here, the analysis of a recently generated Arabidopsis mutant completely devoid of DNA methylation reveals that DNA methylation underpins the genome-wide landscape of histone modifications. Complete loss of DNA methylation causes an upheaval of the histone modification landscape, including complete loss of H3K9me2 and widespread redistribution of active and H3K27me3 histone marks, mostly owing to the role of DNA methylation in initiating H3K9me2 deposition and excluding active marks and repressive mark H3K27me3; CG and non-CG methylation can act independently at some genomic regions while they act cooperatively at many other regions. The transcriptional reprogramming upon loss of all DNA methylation correlates with the extensive redistribution or switches of the examined histone modifications. Histone modifications retained or gained in the DNA methylation-free mutant serve as DNA methylation-independent transcriptional regulatory signals: active marks promote genome transcription, whereas the repressive mark H3K27me3 compensates for the lack of DNA hypermethylation/H3K9me2 at multiple transposon families. Conclusions Our results show that an intact DNA methylome constitutes the scaffolding of the epigenomic landscape in Arabidopsis and is critical for controlled genome transcription and ultimately for proper growth and development.

Abstract Background The laboratory mouse was domesticated from the wild house mouse. Understanding the genetics underlying domestication in laboratory mice, especially in the widely used classical inbred mice, is vital for studies using mouse models. However, the genetic mechanism of laboratory mouse domestication remains unknown due to lack of adequate genomic sequences of wild mice. Results We analyze the genetic relationships by whole-genome resequencing of 36 wild mice and 36 inbred strains. All classical inbred mice cluster together distinctly from wild and wild-derived inbred mice. Using nucleotide diversity analysis, Fst, and XP-CLR, we identify 339 positively selected genes that are closely associated with nervous system function. Approximately one third of these positively selected genes are highly expressed in brain tissues, and genetic mouse models of 125 genes in the positively selected genes exhibit abnormal behavioral or nervous system phenotypes. These positively selected genes show a higher ratio of differential expression between wild and classical inbred mice compared with all genes, especially in the hippocampus and frontal lobe. Using a mutant mouse model, we find that the SNP rs27900929 (T>C) in gene Astn2 significantly reduces the tameness of mice and modifies the ratio of the two Astn2 (a/b) isoforms. Conclusion Our study indicates that classical inbred mice experienced high selection pressure during domestication under laboratory conditions. The analysis shows the positively selected genes are closely associated with behavior and the nervous system in mice. Tameness may be related to the Astn2 mutation and regulated by the ratio of the two Astn2 (a/b) isoforms.

The role of chemokines in predicting the prognosis of colon cancer has not been mentioned. Chemokines have been shown to be associated with immune cell chemotaxis and activation, so the expression of chemokine genes in tumor tissue may be related to prognosis. We used a least absolute shrinkage and selection operator (LASSO) model based on chemokine gene families to construct a model that can predict the prognosis of colon cancer patients. We divided patients into high-risk groups and low-risk groups to study the prognosis. Then, we evaluated the relationship between the different risk groups in infiltration of immune cells. It was found that there was less immune cell infiltration in the high-risk group. We conducted a functional enrichment analysis based on model stratification, and explored the biological signal pathways enriched in the high and low-risk groups, which provided ideas for studying the mechanism behind its impact on prognosis. In addition, the chemokine-related gene signature could predict the response of patients to immunotherapy and chemotherapy.