A synthetic bacterial consortium improved the phytoremediation efficiency of ryegrass on polymetallic contaminated soil.

Polymetallic contamination of soils caused by mining activities seriously threatens soil fertility, biodiversity and human health. Bioremediation is thought to be of low cost and has minimal environmental risk but its effectiveness needs to be improved. This study aimed to identify the combined effect of plant growth and microbial strains with different functions on the enhancement of bioremediation of polymetallic contaminated soil. The microbiological mechanism of bioremediation was explored by amplicon sequencing and gene prediction. Soil was collected from polymetallic mine wastelands and a non-contaminated site for use in a pot experiment. Remediation efficiency of this method was evaluated by planting ryegrass and applying a mixed bacterial consortium comprising P-solubilizing, N-fixing and SO4-reducing bacteria. The plant-microbe joint remediation method significantly enhanced the above-ground biomass of ryegrass and soil nutrient contents, and at the same time reduced the content of heavy metals in the plant shoots and soil. The application of the composite bacterial inoculum significantly affected the structure of soil bacterial communities and increased the bacterial diversity and complexity, and the stability of co-occurrence networks. The relative abundance of the multifunctional genera to which the strains belonged showed a significant positive correlation with the soil nutrient content. Genera related to carbon (C), nitrogen (N), phosphorus (P), and sulphur (S) cycling and heavy metal resistance showed an up-regulation trend in heavy metal-contaminated soils after the application of the mixed bacterial consortium. Also, bacterial strains with specific functions in the mixed consortium regulated the expression of genes involved in soil nutrient cycling, and thus assisted in making the soil self-sustainable after remediation. These results suggested that the remediation of heavy metal-contaminated soil needs to give priority to the use of multifunctional bacterial agents.

Identification of differentially expressed genes of blood leukocytes for Schizophrenia.

Background: Schizophrenia (SCZ) is a severe neurodevelopmental disorder with brain dysfunction. This study aimed to use bioinformatic analysis to identify candidate blood biomarkers for SCZ. Methods: The study collected peripheral blood leukocyte samples of 9 SCZ patients and 20 healthy controls for RNA sequencing analysis. Bioinformatic analyses included differentially expressed genes (DEGs) analysis, pathway enrichment analysis, and weighted gene co-expression network analysis (WGCNA). Results: This study identified 1,205 statistically significant DEGs, of which 623 genes were upregulated and 582 genes were downregulated. Functional enrichment analysis showed that DEGs were mainly enriched in cell chemotaxis, cell surface, and serine peptidase activity, as well as involved in Natural killer cell-mediated cytotoxicity. WGCNA identified 16 gene co-expression modules, and five modules were significantly correlated with SCZ (p < 0.05). There were 106 upregulated genes and 90 downregulated genes in the five modules. The top ten genes sorted by the Degree algorithm were RPS28, BRD4, FUS, PABPC1, PCBP1, PCBP2, RPL27A, RPS21, RAG1, and RPL27. RAG1 and the other nine genes belonged to the turquoise and pink module respectively. Pathway enrichment analysis indicated that these 10 genes were mainly involved in processes such as Ribosome, cytoplasmic translation, RNA binding, and protein binding. Conclusion: This study finds that the gene functions in key modules and related enrichment pathways may help to elucidate the molecular pathogenesis of SCZ, and the potential of key genes to become blood biomarkers for SCZ warrants further validation.

Active Beam Steering Enabled by Photonic-Crystal Surface-Emitting Laser.

Emitting light toward on-demand directions is important for various optoelectronic applications, such as optical communication, displaying, and ranging. However, almost all existing directional emitters are assemblies of passive optical antennae and external light sources, which are usually bulky and fragile and show unendurable loss of light power. Here we theoretically propose and experimentally demonstrate a conceptual design of a directional emitter, by using a single surface-emitting laser source itself to achieve dynamically controlled beam steering. The laser is built on photonic crystals that operate near the band edges in the continuum. By shrinking laser sizes to tens-of-wavelength, the optical modes quantize in three-dimensional momentum space, and each of them directionally radiates toward the far-field. Further utilizing the luminescence spectrum shifting effect under current injection, we consecutively select a sequence of modes into lasing action and show the laser maintaining single-mode operation with line widths at a minimum of 1.8 MHz and an emitting power of ∼10 milliwatts, and we demonstrate fast beam steering across a range of 3.2° × 4° on a time scale of 500 ns. Our work proposes a method for on-chip active beam steering for the development of automotive, industrial, and robotic applications.

Investigating the mechanism and the effect of aquaporin 5 (AQP5) on the self-renewal capacity of gastric cancer stem cells.

Aquaporin 5 (AQP5) has been shown to have a pro-carcinogenic effect in numerous types of malignancies. This research intends to investigate the role and the molecular mechanism of AQP5 on enriched gastric cancer stem cells (GCSCs). Methods: Immunohistochemistry, western blot (WB), and RT-qPCR techniques were employed to identify the presence of AQP5 in gastric cancer (GC) and the neighboring paracancerous tissues. Additionally, a statistical analysis was conducted to determine the correlation between AQP5 expression and the pathological and histological parameters. Furthermore, the study aimed to assess the predictive value of AQP5 expression in long-term survival after GC surgery. GCSCs were enriched using the serum-free culture method. The expression of AQP5 in enriched GCSCs was explored using RT-qPCR and WB. Plate cloning, transwell, WB, RT-qPCR, and the sphere-forming assay were utilized to monitor the proliferation, migration, and self-renewal capability of GCSCs after AQP5 knockdown. WB and Immunofluorescence for Detecting the Effect of AQP5 on Autophagy. WB, RT-qPCR, and other experiments were used for in-depth investigation of the potential molecular regulatory mechanism of AQP5 in GC. Results: AQP5 was highly expressed in GC tissues and GC cells, and overexpression of AQP5 was associated with lymph node metastasis, increased tumor size, and low 5-year postoperative survival in GC patients; other studies have shown that the AQP5 was highly expressed in GCSCs. Knockdown of AQP5 suppressed tumorigenesis in vivo and inhibited the proliferative, migratory, and self-renewal capability of GCSCs. It was also found that AQP5 could activate the autophagy phenomenon of GCSCs, and mechanistically, we found that AQP5 could regulate TRPV4 to affect the self-renewal ability of GCSCs. Conclusion: AQP5 can be further explored for GC therapy, as it has shown a significant impact on the self-renewal capability of GCSCs, which prevents GC progression.

The association between endometrial polyps and insulin resistance from the expression of PI3K and AKT proteins perspective.

BACKGROUND: Insulin resistance (IR) induces hyperinsulinemia, which activates downstream signaling pathways such as the phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) pathway, ultimately leading to abnormal proliferation and apoptosis of endometrial cells. This is thought to be a key pathogenic mechanism underlying the development of endometrial polyps (EP). This study aims to investigate the relationship between IR and the development of EP, the expression levels of downstream signaling molecules, including PI3K and AKT, and related laboratory parameters were examined. METHODS: A total of 100 patients who visited the gynecology outpatient clinic of Zhongda Hospital affiliated with Southeast University from May 2021 to March 2023 and were diagnosed with abnormal endometrial echoes by vaginal ultrasound and underwent hysteroscopic diagnostic curettage were enrolled in this study. General data and relevant hematological indicators were compared, and intraoperative specimens were obtained for pathological examination. Possible factors influencing the development of endometrial polyps were analyzed using Pearson correlation analysis and logistic regression analysis. RESULTS: In terms of body mass index, waist circumference, fasting insulin, insulin resistance index, serum total testosterone, and free testosterone index, women of childbearing age in the endometrial polyp group had higher values than those in the non-polyp group, while sex hormone-binding globulin in the endometrial polyp group was lower than that in the non-polyp group, and the differences were statistically significant (P < 0.05). The expression scores and mRNA expression levels of PI3K and AKT proteins were higher in the EP group than in the non-EP group (p < 0.05). Pearson correlation analysis showed a positive correlation between HOMA-IR and the expression scores of PI3K and AKT proteins (p < 0.01). CONCLUSIONS: Insulin resistance and abnormal activation of the phosphatidylinositol 3-kinase/protein kinase B signaling pathway may be potential pathogenic mechanisms for the development of endometrial polyps.

Comparative effects of different metals on the Japanese medaka embryos and larvae.

Rapid evaluation of the toxicity of metals using fish embryo acute toxicity is facilitative to ecological risk assessment of aquatic organisms. However, this approach has seldom been utilized for the comparative study on the effects of different metals to fish. In this study, acute and sub-chronic tests were used to compare the toxicity of Se(IV) and Cd in the embryos and larvae of Japanese medaka (Oryzias latipes). The embryos with different levels of dechorionation and/or pre-exposure were also exposed to Se(IV) and Cd at various concentrations. The results showed that the LC50-144 h of Cd was 1.3-5.2 folds higher than that of Se(IV) for the embryos. In contrast, LC50-96 h of Se(IV) were 200-400 folds higher than that of Cd for the larvae. Meanwhile, dechorionated embryos were more sensitive to both Se and Cd than the intact embryos. At elevated concentrations, both Se and Cd caused mortality and deformity in the embryos and larvae. In addition, pre-exposure to Cd at the embryonic stages enhanced the resistance to Cd in the larvae. However, pre-exposure to Se(IV) at the embryonic stages did not affect the toxicity of Se(IV) to the larvae. This study has distinguished the nuance differences in effects between Se(IV) and Cd after acute and sub-chronic exposures with/without chorion. The approach might have a potential in the comparative toxicology of metals (or other pollutants) and in the assessment of their risks to aquatic ecosystems.

Human Umbilical Cord Mesenchymal Stem Cell-derived Exosomes Induce Macrophage M2 Polarization by Antagonizing LPS-mediated Stimulation of the NF-κB and STAT3 Pathways.

BACKGROUND: Many studies have documented the protective effects of regulating macrophage M1/M2 polarization in inflammatory diseases characterized by their imbalance state. In pathological diseases associated with inflammation, mesenchymal stem cells (MSCs) regulate macrophages, thereby having anti-inflammatory and tissue regenerative effects. Exosomes have been suggested as an alternative mechanism that underlies the paracrine function of MSCs. Thus, this study explored the anti-inflammatory impact of human umbilical cord MSCssecreted exosomes (hucMSCs-EX) by influencing macrophage polarization in normal and inflammatory environments in vitro. METHODS: In this study, hucMSCs-conditioned medium (hucMSCs-CM) and hucMSCs- EX were used to treat RAW264.7 macrophages with or without LPS. The expressions of TNF- α, IL-10, IL-6, IL-1ß, and Arg-1 were quantified by qPCR. The expressions of IL-6 and IL-10 were evaluated by ELISAs. Western blots (WB) were performed to observe the expressions of CD206, NF-κB P65, NF-κB p-p65, p-STAT3, STAT3, and NF-κB phosphorylation. The number of cells expressing CD206 and the fluorescence intensity were measured via flow cytometry (FC) and immunofluorescence staining. Cell propagation and migration were examined via MTT and transwell assays, respectively. RESULTS: The inhibition of LPS-induced inflammatory polarization by hucMSCs-EX or hucMSCs- CM led to increases in IL-10 and arginase (Arg) levels and decreases in those of IL-6 and TNF-α. Moreover, hucMSCs-EX enhanced the CD206 expression in RAW264.7 cells and accelerated the propagation and migration of LPS-induced cells. The suppressive impact of hucMSCs-EX on the LPS-induced phenotypic polarization of M1 macrophages was linked with the reduction of NF-κB signaling. They stimulated the transition of M2 macrophages by enhancing the activity of STAT3 in RAW264.7 cells. CONCLUSION: This study indicated that hucMSCs-EX enhances the macrophage transition into the M2 phenotype by inhibiting the NF-κB p65 axis and stimulating that of STAT3.

Advances in PGD2/PTGDR2 signaling pathway in tumors: A review.

Studies have shown that the prostaglandin (PG) family acts as allergic inflammatory mediator in malignant diseases. Furthermore, prostaglandin E2 (PGE2) and its related receptors, as well as the prostaglandin D2 (PGD2)/PGD2 receptor (PTGDR2), play irreplaceable roles in tumorigenesis and anti-tumor therapy. Several experiments have demonstrated that PGD2 signaling through PTGDR2 not only directly inhibits cancer cell survival, proliferation, and migration but also reduces resistance towards conventional chemotherapeutic agents. Recent studies from our and other laboratories have shown that PGD2, its ligands, and related metabolites can significantly alter the tumor microenvironment (TME) by promoting the secretion of chemokines and cytokines, thereby inhibiting tumor progression. Additionally, reduced PGD2 expression has been associated with poor prognosis in patients with gastric, breast, lung, and pancreatic cancers, validating the preclinical findings and their clinical relevance. This review focuses on the current understanding of PGD2/PTGDR2 expression patterns and biological activity in cancer, proposing questions to guide the assessment of PGD2 and its receptors as potential targets for effective cancer therapies.

Effects of four antibiotics on the photosynthetic light reactions in the green alga Chlorella pyrenoidosa.

Antibiotics are ubiquitously present in aquatic environments, posing a serious ecological risk to aquatic ecosystems. However, the effects of antibiotics on the photosynthetic light reactions of freshwater algae and the underlying mechanisms are relatively less understood. In this study, the effects of 4 representative antibiotics (clarithromycin, enrofloxacin, tetracycline, and sulfamethazine) on a freshwater alga (Chlorella pyrenoidosa) and the associated mechanisms, primarily focusing on key regulators of the photosynthetic light reactions, were evaluated. Algae were exposed to different concentrations of clarithromycin (0.0-0.3 mg/L), enrofloxacin (0.0-30.0 mg/L), tetracycline (0.0-10.0 mg/L), and sulfamethazine (0.0-50.0 mg/L) for 7 days. The results showed that the 4 antibiotics inhibited the growth, the photosynthetic pigment contents, and the activity of antioxidant enzymes. In addition, exposure to clarithromycin caused a 118.4 % increase in malondialdehyde (MDA) levels at 0.3 mg/L. Furthermore, the transcripts of genes for the adenosine triphosphate (ATP) - dependent chloroplast proteases (ftsH and clpP), genes in photosystem II (psbA, psbB, and psbC), genes related to ATP synthase (atpA, atpB, and atpH), and petA (related to cytochrome b6/f complex) were altered by clarithromycin. This study contributes to a better understanding of the risk of antibiotics on primary producers in aquatic environment.

Pretreatment with interleukin-15 attenuates inflammation and apoptosis by inhibiting NF-κB signaling in sepsis-induced myocardial dysfunction.

Sepsis-induced myocardial dysfunction (SIMD) is associated with poor prognosis and increased mortality in patients with sepsis. Cytokines are important regulators of both the initiation and progression of sepsis. Interleukin-15 (IL-15), a pro-inflammatory cytokine, has been linked to protective effects against myocardial infarction and myocarditis. However, the role of IL-15 in SIMD remains unclear. We established a mouse model of SIMD via cecal ligation puncture (CLP) surgery and a cell model of myocardial injury via lipopolysaccharide (LPS) stimulation. IL-15 expression was prominently upregulated in septic hearts as well as cardiomyocytes challenged with LPS. IL-15 pretreatment attenuated cardiac inflammation and cell apoptosis and improved cardiac function in the CLP model. Similar cardioprotective effects of IL-15 pretreatment were observed in vitro. As expected, IL-15 knockdown had the opposite effect on LPS-stimulated cardiomyocytes. Mechanistically, we found that IL-15 pretreatment reduced the expression of the pro-apoptotic proteins cleaved caspase-3 and Bax and upregulated the anti-apoptotic protein Bcl-2. RNA sequencing and Western blotting further confirmed that IL-15 pretreatment suppressed the activation of nuclear factor kappa B (NF-κB) signaling in mice with sepsis. Besides, the addition of NF-κB inhibitor can significantly attenuate cardiomyocyte apoptosis compared to the control findings. Our results suggest that IL-15 pretreatment attenuated the cardiac inflammatory responses and reduced cardiomyocyte apoptosis by partially inhibiting NF-κB signaling in vivo and in vitro, thereby improving cardiac function in mice with sepsis. These findings highlight a promising therapeutic strategy for SIMD.

Ultralow-loss optical interconnect enabled by topological unidirectional guided resonance.

Grating couplers that interconnect photonic chips to off-chip components are crucial for various optoelectronics applications. Despite numerous efforts in past decades, the existing grating couplers are still far from optimal in energy efficiency and thus hinder photonic integration toward a larger scale. Here, we propose a strategy to achieve ultralow-loss grating couplers by using unidirectional guided resonances (UGRs), suppressing the useless downward radiation with no mirror on the bottom. By engineering the dispersion and apodizing the geometry of grating, we experimentally realize a grating coupler with a record-low loss of -0.34 dB and 1-dB bandwidth exceeding 30 nm at the telecom wavelength of 1550 nm and further demonstrate an optic via with a loss of only -0.94 dB. Given that UGRs ubiquitously exist in a variety of grating geometries, our work sheds light on a systematic method to achieve energy-efficient optical interconnect and paves the way to large-scale photonic integration.

Selection Signal Analysis Reveals Hainan Yellow Cattle Are Being Selectively Bred for Heat Tolerance.

Hainan yellow cattle are indigenous Zebu cattle from southern China known for their tolerance of heat and strong resistance to disease. Generations of adaptation to the tropical environment of southern China and decades of artificial breeding have left identifiable selection signals in their genomic makeup. However, information on the selection signatures of Hainan yellow cattle is scarce. Herein, we compared the genomes of Hainan yellow cattle with those of Zebu, Qinchuan, Nanyang, and Yanbian cattle breeds by the composite likelihood ratio method (CLR), Tajima's D method, and identifying runs of homozygosity (ROHs), each of which may provide evidence of the genes responsible for heat tolerance in Hainan yellow cattle. The results showed that 5210, 1972, and 1290 single nucleotide polymorphisms (SNPs) were screened by the CLR method, Tajima's D method, and ROH method, respectively. A total of 453, 450, and 325 genes, respectively, were identified near these SNPs. These genes were significantly enriched in 65 Gene Ontology (GO) functional terms and 11 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways (corrected p < 0.05). Five genes-Adenosylhomocysteinase-like 2, DnaJ heat shock protein family (Hsp40) member C3, heat shock protein family A (Hsp70) member 1A, CD53 molecule, and zinc finger and BTB domain containing 12-were recognized as candidate genes associated with heat tolerance. After further functional verification of these genes, the research results may benefit the understanding of the genetic mechanism of the heat tolerance in Hainan yellow cattle, which lay the foundation for subsequent studies on heat stress in this breed.

Multifunctional cardiac microphysiological system based on transparent ITO electrodes for simultaneous optical measurement and electrical signal monitoring.

Drug-induced cardiotoxicity is a significant contributor to drug recalls, primarily attributed to limitations in existing drug screening platforms. Traditional heart-on-a-chip platforms often employ metallic electrodes to record cardiomyocyte electrical signals. However, this approach hinders direct cardiomyocyte morphology observation and typically yields limited functionality. Consequently, this limitation may lead to an incomplete understanding of cardiomyocyte characteristics. To address these challenges, we introduce a multifunctional cardiac microphysiological system featuring transparent indium tin oxide electrodes. This innovative design aims to overcome the limitations of conventional heart-on-a-chip systems where metal electrodes interfere with the observation of cells and increase the difficulty of subsequent image processing of cell images. In addition to facilitating optical measurement combined with image processing capabilities, this system integrates a range of electrodes with diverse functionalities. These electrodes can realize cellular electrical stimulation, field potential monitoring, and impedance change tracking, enabling a comprehensive investigation of various cardiomyocyte traits. To demonstrate its versatility, we investigate the effects of four cardiac drugs with distinct pharmacological profiles on cardiomyocytes using this system. This platform provides a means for quantitatively and predictively assessing cardiac toxicity, which could be applied to conduct a comprehensive evaluation during the drug discovery process.

Predicting Dysphonia by Measuring Surface Electromyographic Activity of the Supralaryngeal Muscles.

PURPOSE: This study set out to investigate whether individuals with dysphonia, as determined by either self-assessment or clinician-based auditory-perceptual judgment, exhibited differences in perilaryngeal muscle activities using surface electromyography (sEMG) during various phonatory tasks. Additionally, the study aimed to assess the effectiveness of sEMG in identifying dysphonic cases. METHOD: A total of 77 adults (44 women, 33 men, Mage = 30.4 years) participated in this study, with dysphonic cases identified separately using either a 10-item Voice Handicap Index (VHI-10) or clinician-based auditory-perceptual voice quality (APVQ) evaluation. sEMG activities were measured from the areas of suprahyoid and sternocleidomastoid muscles during prolonged vowel /i/ phonations at different pitch and loudness levels. Normalized root-mean-square value against the maximal voluntary contraction (RMS %MVC) of the sEMG signals was obtained for each phonation and compared between subject groups and across phonatory tasks. Additionally, binary logistic regression analysis was performed to determine how the sEMG measures could predict the VHI-10-based or APVQ-based dysphonic cases. RESULTS: Participants who scored above the criteria on either the VHI-10 (n = 29) or APVQ judgment (n = 17) exhibited significantly higher RMS %MVC in the right suprahyoid muscles compared to the corresponding control groups. Although the RMS %MVC value from the right suprahyoid muscles alone was not a significant predictor of self-evaluated dysphonic cases, a combination of the RMS %MVC values from both the right and left suprahyoid muscles significantly predicted APVQ-based dysphonic cases with a 69.66% fair level. CONCLUSIONS: This study found that individuals with dysphonia, as determined by either self-assessment or APVQ judgment, displayed more imbalanced suprahyoid muscle activities in voice production compared to nondysphonic groups. The combination of the sEMG measures from both left and right suprahyoid muscles showed potential as a predictor of dysphonia with a fair level of confidence. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25112804.

Engineered M2 macrophage-derived extracellular vesicles with platelet membrane fusion for targeted therapy of atherosclerosis.

Atherosclerosis is featured as chronic low-grade inflammation in the arteries, which leads to the formation of plaques rich in lipids. M2 macrophage-derived extracellular vesicles (M2EV) have significant potential for anti-atherosclerotic therapy. However, their therapeutic effectiveness has been hindered by their limited targeting capability in vivo. The objective of this study was to create the P-M2EV (platelet membrane-modified M2EV) using the membrane fusion technique in order to imitate the interaction between platelets and macrophages. P-M2EV exhibited excellent physicochemical properties, and microRNA (miRNA)-sequencing revealed that the extrusion process had no detrimental effects on miRNAs carried by the nanocarriers. Remarkably, miR-99a-5p was identified as the miRNA with the highest expression level, which targeted the mRNA of Homeobox A1 (HOXA1) and effectively suppressed the formation of foam cells in vitro. In an atherosclerotic low-density lipoprotein receptor-deficient (Ldlr-/-) mouse model, the intravenous injection of P-M2EV showed enhanced targeting and greater infiltration into atherosclerotic plaques compared to regular extracellular vesicles. Crucially, P-M2EV successfully suppressed the progression of atherosclerosis without causing systemic toxicity. The findings demonstrated a biomimetic platelet-mimic system that holds great promise for the treatment of atherosclerosis in clinical settings.

Research on the characteristics and influencing factors of the spatial correlation network of cultivated land utilization ecological efficiency in the upper reaches of the Yangtze River, China.

Researching the structural characteristics of the spatial correlation network of cultivated land utilization ecological efficiency is of great significance to China's food security and agricultural green and low-carbon development. Taking 47 cities (autonomous prefectures) in the upper reaches of the Yangtze River as the research object, the ecological efficiency of cultivated land utilization from 2010 to 2020 was measured based on the unexpected output model (Super SBM), and the spatial correlation matrix was constructed using the revised gravity model. The structural characteristics of the spatial correlation network were analyzed using the social network model (SNA), and finally, the factors affecting the spatial correlation network of cultivated land utilization ecological efficiency in the upper reaches of the Yangtze River were analyzed through the quadratic assignment procedure (QAP) model. The results show that: (1) the ecological efficiency of cultivated land utilization in the upper reaches of the Yangtze River has been increasing year by year, but the overall level is low, and there is a large gap among provinces. Sichuan Province has the highest average value of 0.605, and Yunnan Province has the lowest average value of 0.359. (2) The ecological efficiency of cultivated land utilization in the upper reaches of the Yangtze River has broken through the provincial boundaries and has formed an obvious spatial correlation network, but the overall density is low, and the network is still relatively loose, needing further development and improvement. Chengdu, Yibin, Luzhou, and other cities are located in the center of the network and have formed four cohesive subgroups. (3)The differences in the level of agricultural economic development, the rural per capita disposable income, the differences in agricultural mechanization intensity, the regional population differences, and spatial adjacency have an impact on the spatial network of ecological efficiency of cultivated land utilization in the upper reaches of the Yangtze River. The difference in the level of agricultural economic development, the rural per capita disposable income, and the differences in agricultural mechanization intensity are negatively correlated, while the regional population differences are positively correlated with spatial adjacency.

Detection of Runs of Homozygosity and Identification of Candidate Genes in the Whole Genome of Tunchang Pigs.

Tunchang pigs are an indigenous pig population in China known for their high tolerance to roughage, delicious meat, and fecundity. However, the number of Tunchang pigs has been declining due to the influence of commercial breeds and African swine fever, which could potentially lead to inbreeding. To assess the inbreeding level and the genetic basis of important traits in Tunchang pigs, our research investigated the patterns in "runs of homozygosity" (ROHs) using whole genome resequencing data from 32 Tunchang pigs. The study aimed to determine the length, number, coverage, and distribution model of ROHs in Tunchang pigs, as well as genomic regions with high ROH frequencies. The results of the study revealed that a total of 20,499,374 single-nucleotide polymorphisms (SNPs) and 1953 ROH fragments were recognized in 32 individuals. The ROH fragments in Tunchang pigs were predominantly short, ranging from 0.5 to 1 megabases (Mb) in length. Furthermore, the coverage of ROHs varied across chromosomes, with chromosome 3 having the highest coverage and chromosome 11 having the lowest coverage. The genetic diversity of Tunchang pigs was found to be relatively high based on the values of HE (expected heterozygosity), HO (observed heterozygosity), pi (nucleotide diversity), Ne (effective population size), and MAF (minor allele frequency). The average inbreeding coefficients of Tunchang pigs, as determined by three different methods (FHOM, FGRM, and FROH), were 0.019, 0.0138, and 0.0304, respectively. These values indicate that the level of inbreeding in Tunchang pigs is currently low. Additionally, the study identified a total of 13 ROH islands on all chromosomes, which in total contained 38,913 SNPs and 120 genes. These ROH islands included genes associated with economically important traits, including meat quality (GYS1, PHLPP1, SLC27A5, and CRTC1), growth and development (ANKS1A, TAF11, SPDEF, LHB, and PACSIN1), and environmental adaptation (SLC26A7). The findings of this research offer valuable perspectives on the present status of Tunchang pig resources and offer a reference for breeding conservation plans and the efficient utilization of Tunchang pigs in the future. By understanding the inbreeding level and genetic basis of important traits in Tunchang pigs, conservation efforts can be targeted towards maintaining genetic diversity and promoting the sustainable development of this indigenous pig population.

Characteristics of gut microbiota and metabolomic of Hainan Tunchang pigs at various growth stages.

Numerous gut microorganisms residing in the gut tract and their metabolites play an important role in animal growth. Diet, as the main factor, affects the changes of gut microbiota, and host genetics also have a significant impact on gut microbiota, including growth stages. However, the differences of gut microbiota and its metabolites at various growth stages in local pig breed remains unclear. We used 16S rRNA gene sequencing and untargeted metabolomics to investigate the fecal microbiota and metabolites in different developmental stages of Hainan Tunchang pigs. The relative proportions of dominant bacteria Firmicutes and Spirochaetes increased, Bacteroidetes and Proteobacteria decreased with the development. As age increased, different physiological states led to structural and functional changes in animal nutrition metabolism and immune needs, as well as changes in gut microbiota and its metabolites. We have detected several statistically different microbial and metabolic biomarkers at different growth stages. Meanwhile, through correlation analysis between differential bacteria and metabolites, it was found that the bacteria forming networks with their significant related metabolites were different at various growth stages, Holdemanella, Sharpea, Subdoligranulum, and uncultured_bacterium_o_Bacteroidales were enriched between preweaning piglets and weaning piglets, and they all positive correlated with related metabolites. We also found that the differential bacteria were significantly related to short-chain fatty acid. These findings might provide new insights into the developmental changes of gut microbiota in local pig breeds and the interaction mechanism between the body, and improve pig growth performance and efficiency by regulating the composition of gut microbiota and metabolites.

Exploring potential causal associations between autoimmune diseases and colorectal cancer using bidirectional Mendelian randomization.

Several observational studies have revealed an association between autoimmune diseases (AIDs) and colorectal cancer (CRC), although their causal association remained controversial. Therefore, our study used a two-sample Mendelian randomization (MR) analysis to verify the causal association between AIDs and CRC. We employed three common MR approaches, including inverse variance weighted (IVW), weighted median, and MR-Egger methods, to assess the causal association between type 1 diabetes (T1D), systemic lupus erythematosus, rheumatoid arthritis, psoriasis, multiple sclerosis, juvenile idiopathic arthritis, celiac disease, and primary sclerosing cholangitis (PSC) and CRC. The reverse MR analysis was performed to assess the possibility of reverse causation. To evaluate the validity of the analysis, we also performed sensitivity analysis, such as the heterogeneity test, the horizontal pleiotropy test, and the leave-one-out sensitivity analysis, and validated the results in the validation cohort. Our results showed that genetically predicted T1D was nominally associated with a lower risk of CRC (IVW OR = 0.965, 95% CI = 0.939-0.992, P = 0.012). However, genetic susceptibility to psoriasis nominally increased the risk of CRC (IVW OR = 1.026, 95% CI = 1.002-1.050, P = 0.037). Genetically predicted PSC had a significant causal effect on the increasing risk of CRC (IVW OR = 1.038, 95% CI = 1.016-1.060, P = 5.85 × 10-4). Furthermore, the MR analysis between PSC and the CRC validation cohort indicated consistent results. We found no causal association between genetically predicted other five AIDs and CRC (P > 0.05). The results of reverse MR analysis showed that genetically predicted CRC had no causal effect on T1D, psoriasis, and PSC (P > 0.05). The sensitivity analysis demonstrated that the results of the MR analysis were reliable. Our findings help to understand the causal association between AIDs and CRC, which deserves further investigation.

Multi-level magnetic microrobot delivery strategy within a hierarchical vascularized organ-on-a-chip.

Targeted microrobotic delivery within the circulatory system holds significant potential for medical theranostic applications. Existing delivery strategies of microrobots encounter challenges such as slow speed, limited navigation control, and dispersal under dynamic flow conditions. Furthermore, within the realm of microrobots, in vitro testing platforms often lack essential biological microenvironments, while in vivo studies conducted on animal models are constrained by limited detection resolution. In this study, we propose a multi-level magnetic delivery strategy that integrates a tethered microrobotic guidewire and untethered swimming microrobots. The amalgamation compensates for their inherent constraints, ensuring a robust and highly efficient delivery of microrobots under complex physiological conditions over extensive distances. Concurrently, a hierarchical vascular network encompassing engineered arteries/veins and capillary networks was constructed by integrating vasculogenesis and endothelial cell (EC) lining strategies, thereby providing an in vivo-like testing platform for microrobots. Experimental evidence demonstrates that the flexible microrobotic guidewire can be precisely directed to any entrance of the second-tier branches, with its inner lumen providing an "express lane" for rapid passage of microrobots through complex fluidic environments without direct contact. After release, dynamically assembled swarms could effectively locomote on the micro-topography of the EC-lined channel surface without becoming trapped and congregate within specified regions inside capillary lumens when guided collectively by a biologically safe magnetic field. Additionally, the superparamagnetic capabilities of microrobotic swarms ensure their dissolution into monodispersed entities upon withdrawal of the magnetic field, mitigating the risk of intravascular thrombosis. The hierarchical vascularized organ-on-a-chip platform establishes a comprehensive testing platform that integrates imaging, control, and a functional 3D microvascular environment, thereby enhancing its suitability for microrobotic applications encompassing targeted drug delivery, thrombus ablation, sensing and diagnosis, etc.