Muscle growth differences in Lijiang pigs revealed by ATAC-seq multi-omics.

As one of the largest tissues in the animal body, skeletal muscle plays a pivotal role in the production and quality of pork. Consequently, it is of paramount importance to investigate the growth and developmental processes of skeletal muscle. Lijiang pigs, which naturally have two subtypes, fast-growing and slow-growing, provide an ideal model for such studies by eliminating breed-related influences. In this study, we selected three fast-growing and three slow-growing 6-month-old Lijiang pigs as subjects. We utilized assay for transposase-accessible chromatin with sequencing (ATAC-seq) combined with genomics, RNA sequencing, and proteomics to screen for differentially expressed genes and transcription factors linked to increased longissimus dorsi muscle volume in Lijiang pigs. We identified 126 genes through ATAC-seq, including PPARA, TNRC6B, NEDD1, and FKBP5, that exhibited differential expression patterns during muscle growth. Additionally, we identified 59 transcription factors, including Foxh1, JunB, Mef2 family members (Mef2a/b/c/d), NeuroD1, and TEAD4. By examining open chromatin regions (OCRs) with significant genetic differentiation, genes such as SAV1, CACNA1H, PRKCG, and FGFR4 were found. Integrating ATAC-seq with transcriptomics and transcriptomics with proteomics, we identified differences in open chromatin regions, transcription, and protein levels of FKBP5 and SCARB2 genes in fast-growing and slow-growing Lijiang pigs. Utilizing multi-omics analysis with R packages, we jointed ATAC-seq, transcriptome, and proteome datasets, identifying enriched pathways related to glycogen metabolism and skeletal muscle cell differentiation. We pinpointed genes such as MYF6 and HABP2 that exhibit strong correlations across these diverse data types. This study provides a multi-faceted understanding of the molecular mechanisms that lead to differences in pig muscle fiber growth.

Tangzu granule alleviate neuroinflammation in diabetic peripheral neuropathy by suppressing pyroptosis through P2X7R /NLRP3 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus, mainly manifested as paresthesia. Tangzu granule (TZG) is derived from famous traditional Chinese medicine decoctions and optimized by long-term temporary practice. TZG has good efficacy in improving numbness, pain and pruritus of the lower extremities of DPN patients. However, the overall regulatory mechanisms underlying its effects on DPN remain unclear. AIM OF THE STUDY: This study aims to explore the potential mechanism of TZG for treating DPN. MATERIALS AND METHODS: Sprague-Dawley (SD) rats were used to establish an in vivo model of DPN with streptozotocin (STZ) injection and high-fat diet (HFD) feeding. Additionally, sciatic glial RSC96 cells were induced with high glucose in vitro. SD rats in intervention group received TZG treatment for 12 weeks. After 12 weeks of treatment, sciatic nerve function was evaluated by intelligent hot plate meter and neuro electrophysiology detector. The morphological changes of sciatic nerve cells were observed by hematoxylin-eosin staining and transmission electron microscope. IL-1ß, IL-18 inflammatory cytokines, pyroptosis and P2X7R/NLRP3 signaling pathway were observed by Western blotting, immunofluorescence staining and ELISA. RESULTS: TZG improved nerve conduction velocity and sciatic neuropathy rational structural changes in DPN rats. It also inhibited RSC96 inflammatory response and cell death that induced by high glucose. This may be related to TZG inhibiting P2X7R, decreasing the activation of NLRP3 inflammasomes, down-regulating the levels of pyroptosis proteins such as caspase-1, cleaved caspase-1, gasdermin D (GSDMD), and GSDMD-N, and inhibiting the release of interleuki (IL)-18 and IL-1ß inflammatory cytokines. CONCLUSIONS: TZG inhibited pyroptosis through P2X7R/NLRP3 signaling pathway, alleviated neuroinflammation, and showed protective effect in the treatment of DPN.

Tumor-associated exosomes in cancer progression and therapeutic targets.

Exosomes are small membrane vesicles that are released by cells into the extracellular environment. Tumor-associated exosomes (TAEs) are extracellular vesicles that play a significant role in cancer progression by mediating intercellular communication and contributing to various hallmarks of cancer. These vesicles carry a cargo of proteins, lipids, nucleic acids, and other biomolecules that can be transferred to recipient cells, modifying their behavior and promoting tumor growth, angiogenesis, immune modulation, and drug resistance. Several potential therapeutic targets within the TAEs cargo have been identified, including oncogenic proteins, miRNAs, tumor-associated antigens, immune checkpoint proteins, drug resistance proteins, and tissue factor. In this review, we will systematically summarize the biogenesis, composition, and function of TAEs in cancer progression and highlight potential therapeutic targets. Considering the complexity of exosome-mediated signaling and the pleiotropic effects of exosome cargoes has challenge in developing effective therapeutic strategies. Further research is needed to fully understand the role of TAEs in cancer and to develop effective therapies that target them. In particular, the development of strategies to block TAEs release, target TAEs cargo, inhibit TAEs uptake, and modulate TAEs content could provide novel approaches to cancer treatment.

[Diagnostic Value of Interleukin 6, Interleukin 12P70, Serum Amyloid A, and Procalcitonin for Rheumatoid Arthritis and Their Relationship With the Disease Activity]. / ç™½ä»‹ç´ 6ã€ç™½ä»‹ç´ 12P70ã€è¡€æ¸ æ·€ç²‰æ ·è›‹ç™½é ¶Aå’Œé™é’™ç´ åŽŸå¯¹ç±»é£Žæ¹¿å ³èŠ‚ç‚Žçš„è¯Šæ–­ä»·å€¼åŠä¸Žç–¾ç— æ´»åŠ¨åº¦çš„å ³ç³».

Objective: To observe the diagnostic value of four serum inflammatory biomarkers, including interleukin 6 (IL-6), interleukin 12P70 (IL-12P70), serum amyloid A (SAA), and procalcitonin (PCT), in rheumatoid arthritis (RA) and to analyze their relationship with the disease activity. Methods: The study included 60 RA patients admitted to the Department of Rheumatology at Anhui Provincial Hospital of Traditional Chinese Medicine between December 2022 and December 2023. Thirty healthy individuals from the hospital's physical examination center served as the control group. Serum levels of IL-6 and IL-12P70 were detected using flow cytometry. SAA levels were determined by immunoturbidimetry, and PCT levels were assessed by chemiluminescence. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), and anticyclic citrullinated peptide (ACCP) were detected using an automated biochemical analyzer. The 28-joint disease activity scores (DAS28-ESR) based on ESR were observed. Statistical analysis included t-tests, rank-sum tests, and Kruskal-Wallis H tests to compare the expression differences of the biomarkers among different groups. The diagnostic value of these biomarkers for RA was analyzed by ROC curve analysis. Spearman correlation analysis was performed to assess the relationships between the four inflammatory biomarkers and CRP, ESR, RF, ACCP, and DAS28-ESR. Results: 1) The expression levels of SAA, IL-6, and IL-12P70 in the RA group were significantly higher than those in the control group (P<0.01). 2) ROC curve analysis showed that the area under the curve (AUC) for PCT was 0.611 (95% confidence interval [CI]: 0.488-0.735, P>0.05), for SAA, it was 0.819 (95% CI: 0.733-0.906, P<0.01), for IL-6, it was 0.875 (95% CI: 0.803-0.946, P<0.01), and for IL-12P70, it was 0.832 (95% CI: 0.746-0.917, P<0.01). The combined index of IL-6, IL-12P70, SAA, and PCT had an AUC of 0.973 (95% CI: 0.942-1.000, P<0.01). This indicates that the four inflammatory biomarkers can assist in the diagnosis of rheumatoid arthritis. 3) The expression levels of PCT and SAA varied significantly among the high, moderate, and low activity RA groups (P<0.01). 4) In RA patients, CRP was positively correlated with SAA (rs =0.75, P<0.01), and IL-6 (rs =0.52, P<0.01). ESR was positively correlated with SAA (rs =0.36, P<0.01). DAS28-ESR was positively correlated with PCT (rs =0.34, P=0.01), SAA (rs =0.51, P<0.01) and IL-6 (rs =0.33, P=0.01). Conclusion: The four inflammatory biomarkers (PCT, SAA, IL-6, and IL-12P70) are closely related to rheumatoid arthritis disease activity and can serve as serum indicators to assist in the diagnosis and assessment of RA.

[The application of inflammation-related cytokines in early diagnosis and disease assessment of rheumatoid arthritis].

Objective To measure the serum contents of cytokines in patients with rheumatoid arthritis (RA) and explore the clinical application value of combined detection of inflammatory cytokines in evaluating the severity of RA. Methods This study recruited 28 RA patients and 15 healthy individuals who received health checkups during the same period. The expression of inflammatory cytokines including interleukin 1ß (IL-1ß), IL-2, IL-5, IL-6, IL-8, IL-12P70, IL-17, tumor necrosis factor-α (TNF-α), interferon α (IFN-α), IFN-γ, IL-4 and IL-10 were detected with the multiplexed microsphere-based flow cytometric immunoassay. C-reactive protein (CRP) was detected with an automatic biochemical instrument, and erythrocyte sedimentation rate (ESR) was measured by the Westergren method. The disease activity score in 28 joints (DAS28) in the RA group was calculated, and the area under the curve (AUC) of each cytokine and RA disease activity was compared. The correlation of serum levels of inflammatory cytokines with CRP and ESR was analyzed in RA patients. Results In RA patients, the serum levels of IL-2, IL-6, IL-12P70, IL-4 and IL-10 were significantly correlated with the indicator of RA disease activity DAS28-CRP, and the serum levels of IL-12P70, TNF-α and IL-4 were markedly correlated with the indicator of RA disease activity DAS28-ESR. CRP was positively correlated with IL-6 (r=0.515), IL-12P70 (r=0.530), IL-4 (r=0.539), and IL-10(r=0.434). ESR was positively correlated with IL-6 (r=0.403), IL-12P70 (r=0.475), TNF-α (r=0.497), and IL-4 (r=0.450). Compared with the normal CRP and ESR group, the abnormal CRP group showed an increase in the levels of IL-6, IL-12P70, IL-2, IL-4 and IL-10, and the abnormal ESR group exhibited an elevation in the levels of IL-12P70, IL-4 and TNF-α. The expression of IL-8, IFN-α and IFN-γ was higher in the experimental group than in the control group. Conclusion Serum inflammatory cytokines detection has shed light on the early diagnosis and severity evaluation of RA and can be used as a pivotal indcator for the diagnosis of RA.

Tumor necrosis factor α deficiency promotes myogenesis and muscle regeneration.

Tumor necrosis factor α (TNFα) exhibits diverse biological functions; however, its regulatory roles in myogenesis are not fully understood. In the present study, we explored the function of TNFα in myoblast proliferation, differentiation, migration, and myotube fusion in primary myoblasts and C2C12 cells. To this end, we constructed TNFα muscle-conditional knockout ( TNFα-CKO) mice and compared them with flox mice to assess the effects of TNFα knockout on skeletal muscles. Results indicated that TNFα-CKO mice displayed phenotypes such as accelerated muscle development, enhanced regenerative capacity, and improved exercise endurance compared to flox mice, with no significant differences observed in major visceral organs or skeletal structure. Using label-free proteomic analysis, we found that TNFα-CKO altered the distribution of several muscle development-related proteins, such as Hira, Casz1, Casp7, Arhgap10, Gas1, Diaph1, Map3k20, Cfl2, and Igf2, in the nucleus and cytoplasm. Gene set enrichment analysis (GSEA) further revealed that TNFα deficiency resulted in positive enrichment in oxidative phosphorylation and MyoD targets and negative enrichment in JAK-STAT signaling. These findings suggest that TNFα-CKO positively regulates muscle growth and development, possibly via these newly identified targets and pathways.

Genome-wide identification of quantitative trait loci and candidate genes for seven carcass traits in a four-way intercross porcine population.

BACKGROUND: Carcass traits are essential economic traits in the commercial pig industry. However, the genetic mechanism of carcass traits is still unclear. In this study, we performed a genome-wide association study (GWAS) based on the specific-locus amplified fragment sequencing (SLAF-seq) to study seven carcass traits on 223 four-way intercross pigs, including dressing percentage (DP), number of ribs (RIB), skin thinkness (ST), carcass straight length (CSL), carcass diagonal length (CDL), loin eye width (LEW), and loin eye thickness (LET). RESULTS: A total of 227,921 high-quality single nucleotide polymorphisms (SNPs) were detected to perform GWAS. A total of 30 SNPs were identified for seven carcass traits using the mixed linear model (MLM) (p < 1.0 × 10- 5), of which 9 SNPs were located in previously reported quantitative trait loci (QTL) regions. The phenotypic variation explained (PVE) by the significant SNPs was from 2.43 to 16.32%. Furthermore, 11 candidate genes (LYPLAL1, EPC1, MATN2, ZFAT, ZBTB10, ZNF704, INHBA, SMYD3, PAK1, SPTBN2, and ACTN3) were found for carcass traits in pigs. CONCLUSIONS: The GWAS results will improve our understanding of the genetic basis of carcass traits. We hypothesized that the candidate genes associated with these discovered SNPs would offer a biological basis for enhancing the carcass quality of pigs in swine breeding.

Transcriptomic Analyses Reveal the Effects of Walnut Kernel Cake on Adipose Deposition in Pigs.

With the rising cost of animal feed protein, finding affordable and effective substitutes is crucial. Walnut kernel cake, a polyphenol-, fiber-, protein- and fat-rich byproduct of walnut oil extraction, has been underexplored as a potential protein replacement in pig feed. In this study, we found that feeding large Diqing Tibetan pigs walnut kernel cake promoted adipose deposition and improved pork quality during pig growth. Transcriptome analysis revealed the upregulation of genes ANGPTL8, CCNP, ETV4, and TRIB3, associated with adipose deposition. Pathway analysis highlighted enrichment in adipose deposition-related pathways, including PPAR, insulin, PI3K-Akt, Wnt, and MAPK signaling. Further analysis identified DEGs (differentially expressed genes) positively correlated with adipose-related traits, such as PER2 and PTGES. Single-cell transcriptome data pointed to the specific expression of CD248 and PTGES in adipocyte progenitor/stem cells (APSCs), pivotal for adipocyte differentiation and adipose deposition regulation. This study demonstrates walnut kernel cake's potential to substitute soybean cake in pig feed, providing high-quality protein and promoting adipose deposition. It offers insights into feed protein replacement, human functional food, fat metabolism, and related diseases, with marker genes and pathways supporting pig breeding and pork quality improvement.

CuSO4/H2O2induced polydopamine/polysulfobetaine methacrylate co-deposition on poly(amino acid) membranes for improved anti-protein adsorption and antibacterial activity.

Stopping postoperative soft tissue adhesions is one of the most challenging clinical problems that needs to be addressed urgently to avoid secondary injury and pain to patients. Currently, membrane materials with anti-protein adsorption and antibacterial activity are recognized as an effective and promising anti-adhesion barrier to prevent postoperative adhesion and the recurrent adhesion after adhesiolysis. Herein, poly(amino acid) (PAA), which is structurally similar to collagen, is selected as the membrane base material to successfully synthesize PAA-5 membranes with excellent mechanical and degradation properties by in-situ melt polymerization and hot-melt film-forming technology. Subsequently, the co-deposition of polydopamine/polysulfobetaine methacrylate (PDA/PSBMA) coatings induced by CuSO4/H2O2on PAA-5 membranes results in the formation of PDC-5S and PDC-10S, which exhibit excellent hemocompatibility, protein antifouling properties, and cytocompatibility. Additionally, PDC-5S and PDC-10S demonstrated significant antibacterial activity againstEscherichia coliandStaphylococcus aureus, with an inhibition rate of more than 90%. As a result, this study sheds light on newly discovered PAA membranes with anti-protein adsorption and antibacterial activity can sever as one of the promising candidates for the prevention of postoperative peritoneum adhesions.

Expression of PDLIM5 Spliceosomes and Regulatory Functions on Myogenesis in Pigs.

Meat yield, determined by muscle growth and development, is an important economic trait for the swine industry and a focus of research in animal genetics and breeding. PDZ and LIM domain 5 (PDLIM5) are cytoskeleton-related proteins that play key roles in various tissues and cells. These proteins have multiple isoforms, primarily categorized as short (PDLIM5-short) and long (PDLIM5-long) types, distinguished by the absence and presence of an LIM domain, respectively. However, the expression patterns of swine PDLIM5 isoforms and their regulation during porcine skeletal muscle development remain largely unexplored. We observed that PDLIM5-long was expressed at very low levels in pig muscles and that PDLIM5-short and total PDLIM5 were highly expressed in the muscles of slow-growing pigs, suggesting that PDLIM5-short, the dominant transcript in pigs, is associated with a slow rate of muscle growth. PDLIM5-short suppressed myoblast proliferation and myogenic differentiation in vitro. We also identified two single nucleotide polymorphisms (-258 A > T and -191 T > G) in the 5' flanking region of PDLIM5, which influenced the activity of the promoter and were associated with muscle growth rate in pigs. In summary, we demonstrated that PDLIM5-short negatively regulates myoblast proliferation and differentiation, providing a theoretical basis for improving pig breeding programs.

Genetic introgression from commercial European pigs to the indigenous Chinese Lijiang breed and associated changes in phenotypes.

BACKGROUND: Gene flow is crucial for enhancing economic traits of livestock. In China, breeders have used hybridization strategies for decades to improve livestock performance. Here, we performed whole-genome sequencing of a native Chinese Lijiang pig (LJP) breed. By integrating previously published data, we explored the genetic structure and introgression of genetic components from commercial European pigs (EP) into the LJP, and examined the impact of this introgression on phenotypic traits. RESULTS: Our analysis revealed significant introgression of EP breeds into the LJP and other domestic pig breeds in China. Using a haplotype-based approach, we quantified introgression levels and compared EP to LJP and other Chinese domestic pigs. The results show that EP introgression is widely prevalent in Chinese domestic pigs, although there are significant differences between breeds. We propose that LJP could potentially act as a mediator for the transmission of EP haplotypes. We also examined the correlation between EP introgression and the number of thoracic vertebrae in LJP and identified VRTN and STUM as candidate genes for this trait. CONCLUSIONS: Our study provides evidence of introgressed European haplotypes in the LJP breed and describes the potential role of EP introgression on phenotypic changes of this indigenous breed.

APP1/NTL9-CalS8 module ensures proper phloem differentiation by stabilizing callose accumulation and symplastic communication.

Phloem sieve elements (PSE), the primary conduits collaborating with neighboring phloem pole pericycle (PPP) cells to facilitate unloading in Arabidopsis roots, undergo a series of developmental stages before achieving maturation and functionality. However, the mechanism that maintains the proper progression of these differentiation stages remains largely unknown. We identified a gain-of-function mutant altered phloem pole pericycle 1 Dominant (app1D), producing a truncated, nuclear-localized active form of NAC with Transmembrane Motif 1-like (NTL9). This mutation leads to ectopic expression of its downstream target CALLOSE SYNTHASE 8 (CalS8), thereby inducing callose accumulation, impeding SE differentiation, impairing phloem transport, and inhibiting root growth. The app1D phenotype could be reproduced by blocking the symplastic channels of cells within APP1 expression domain in wild-type (WT) roots. The WT APP1 is primarily membrane-tethered and dormant in the root meristem cells but entries into the nucleus in several cells in PPP near the unloading region, and this import is inhibited by blocking the symplastic intercellular transport in differentiating SE. Our results suggest a potential maintenance mechanism involving an APP1-CalS8 module, which induces CalS8 expression and modulates symplastic communication, and the proper activation of this module is crucial for the successful differentiation of SE in the Arabidopsis root.

Self-Supervised Node Representation Learning via Node-to-Neighbourhood Alignment.

Self-supervised node representation learning aims to learn node representations from unlabelled graphs that rival the supervised counterparts. The key towards learning informative node representations lies in how to effectively gain contextual information from the graph structure. In this work, we present simple-yet-effective self-supervised node representation learning via aligning the hidden representations of nodes and their neighbourhood. Our first idea achieves such node-to-neighbourhood alignment by directly maximizing the mutual information between their representations, which, we prove theoretically, plays the role of graph smoothing. Our framework is optimized via a surrogate contrastive loss and a Topology-Aware Positive Sampling (TAPS) strategy is proposed to sample positives by considering the structural dependencies between nodes, which enables offline positive selection. Considering the excessive memory overheads of contrastive learning, we further propose a negative-free solution, where the main contribution is a Graph Signal Decorrelation (GSD) constraint to avoid representation collapse and over-smoothing. The GSD constraint unifies some of the existing constraints and can be used to derive new implementations to combat representation collapse. By applying our methods on top of simple MLP-based node representation encoders, we learn node representations that achieve promising node classification performance on a set of graph-structured datasets from small- to large-scale.

E3 ligases MAC3A and MAC3B ubiquitinate UBIQUITIN-SPECIFIC PROTEASE14 to regulate organ size in Arabidopsis.

The molecular mechanisms controlling organ size during plant development ultimately influence crop yield. However, a deep understanding of these mechanisms is still lacking. UBIQUITIN-SPECIFIC PROTEASE14 (UBP14), encoded by DA3, is an essential factor determining organ size in Arabidopsis (Arabidopsis thaliana). Here, we identified two suppressors of the da3-1 mutant phenotype, namely SUPPRESSOR OF da3-1 1 and 2 (SUD1 and SUD2), which encode the E3 ligases MOS4-ASSOCIATED COMPLEX 3A (MAC3A) and MAC3B, respectively. The mac3a-1 and mac3b-1 mutations partially suppressed the high ploidy level and organ size phenotypes observed in the da3-1 mutant. Biochemical analysis showed that MAC3A and MAC3B physically interacted with and ubiquitinated UBP14/DA3 to modulate its stability. We previously reported that UBP14/DA3 acts upstream of the B-type cyclin-dependent kinase CDKB1;1 and maintains its stability to inhibit endoreduplication and cell growth. In this work, MAC3A and MAC3B were found to promote the degradation of CDKB1;1 by ubiquitinating UBP14/DA3. Genetic analysis suggests that MAC3A and MAC3B act in a common pathway with UBP14/DA3 to control endoreduplication and organ size. Thus, our findings define a regulatory module, MAC3A/MAC3B-UBP14-CDKB1;1, that plays a critical role in determining organ size and endoreduplication in Arabidopsis.

AGIDB: a versatile database for genotype imputation and variant decoding across species.

The high cost of large-scale, high-coverage whole-genome sequencing has limited its application in genomics and genetics research. The common approach has been to impute whole-genome sequence variants obtained from a few individuals for a larger population of interest individually genotyped using SNP chip. An alternative involves low-coverage whole-genome sequencing (lcWGS) of all individuals in the larger population, followed by imputation to sequence resolution. To overcome limitations of processing lcWGS data and meeting specific genotype imputation requirements, we developed AGIDB (https://agidb.pro), a website comprising tools and database with an unprecedented sample size and comprehensive variant decoding for animals. AGIDB integrates whole-genome sequencing and chip data from 17 360 and 174 945 individuals, respectively, across 89 species to identify over one billion variants, totaling a massive 688.57 TB of processed data. AGIDB focuses on integrating multiple genotype imputation scenarios. It also provides user-friendly searching and data analysis modules that enable comprehensive annotation of genetic variants for specific populations. To meet a wide range of research requirements, AGIDB offers downloadable reference panels for each species in addition to its extensive dataset, variant decoding and utility tools. We hope that AGIDB will become a key foundational resource in genetics and breeding, providing robust support to researchers.

Evidential support for garlic supplements against diabetic kidney disease: a preclinical meta-analysis and systematic review.

Garlic (Allium sativum L.) is a popular spice that is widely used for food and medicinal purposes and has shown potential effects on diabetic kidney disease (DKD). Nevertheless, systematic preclinical studies are still lacking. In this meta-analysis and systematic review, we evaluated the role and potential mechanisms of action of garlic and its derived components in animal models of DKD. We searched eight databases for relevant studies from the establishment of the databases to December 2022 and updated in April 2023 before the completion of this review. A total of 24 trials were included in the meta-analysis. It provided preliminary evidence that supplementing with garlic could improve the indicators of renal function (BUN, Scr, 24 h urine volume, proteinuria, and KI) and metabolic disorders (BG, insulin, and body weight). Meanwhile, the beneficial effects of garlic and its components in DKD could be related to alleviating oxidative stress, suppressing inflammatory reactions, delaying renal fibrosis, and improving glucose metabolism. Furthermore, time-dose interval analysis exhibited relatively greater effectiveness when garlic products were supplied at doses of 500 mg kg-1 with interventions lasting 8-10 weeks, and garlic components were administered at doses of 45-150 mg kg-1 with interventions lasting 4-10 weeks. This meta-analysis and systematic review highlights for the first time the therapeutic potential of garlic supplementation in animal models of DKD and offers a more thorough evaluation of its effects and mechanisms to establish an evidence-based basis for designing future clinical trials.

326K at E Protein Is Critical for Mammalian Adaption of TMUV.

Outbreaks of Tembusu virus (TMUV) infection have caused huge economic losses to the poultry industry in China since 2010. However, the potential threat of TMUV to mammals has not been well studied. In this study, a TMUV HB strain isolated from diseased ducks showed high virulence in BALB/c mice inoculated intranasally compared with the reference duck TMUV strain. Further studies revealed that the olfactory epithelium is one pathway for the TMUV HB strain to invade the central nervous system of mice. Genetic analysis revealed that the TMUV HB virus contains two unique residues in E and NS3 proteins (326K and 519T) compared with duck TMUV reference strains. K326E substitution weakens the neuroinvasiveness and neurovirulence of TMUV HB in mice. Remarkably, the TMUV HB strain induced significantly higher levels of IL-1ß, IL-6, IL-8, and interferon (IFN)-α/ß than mutant virus with K326E substitution in the brain tissue of the infected mice, which suggested that TMUV HB caused more severe inflammation in the mouse brains. Moreover, application of IFN-ß to infected mouse brain exacerbated the disease, indicating that overstimulated IFN response in the brain is harmful to mice upon TMUV infection. Further studies showed that TMUV HB upregulated RIG-I and IRF7 more significantly than mutant virus containing the K326E mutation in mouse brain, which suggested that HB stimulated the IFN response through the RIG-I-IRF7 pathway. Our findings provide insights into the pathogenesis and potential risk of TMUV to mammals.

Cu-doped mesoporous SnO2 nanoparticles with rich grain boundaries and oxygen vacancies for photocatalytic CO2-to-CO conversion.

Photocatalytic conversion of carbon dioxide into fuels provides an effective approach to realize carbon resource utilization. However, the photocatalytic efficiency is still relatively low due to the recombination of photogenerated charges. Herein, we have designed Cu-doped SnO2 nanoparticles (Cu-SnO2) using a glucose-involved hydrothermal crystallization method for the photocatalytic reduction of CO2. The rich oxygen vacancies facilitated the separation and transfer of photogenerated charges, and the confined effect of the typical mesoporous structure promoted the adsorption of CO2, especially a high density of grain boundaries (GBs) and the doping of atomic Cu would introduce new active sites to activate CO2 molecules. This elaborately designed catalyst exhibited super and stable photocatalytic conversion activity of CO2-into-CO, with a CO optimal yield of 107 µmol g-1 in 4 h, which was 2.75 times that over pure SnO2. In situ Raman results indicated that the CO2 reduction reaction followed a *COOH pathway on Cu-SnO2. This work provides implications for the construction of a catalyst with rich defects in the field of energy and environmental catalysis.

Conserved and unique functions of NIN-like proteins in nitrate sensing and signaling.

Nitrogen is the most abundant element in the atmosphere and serves as the foundation block of life, including plants on earth. Unlike carbon fixation through photosynthesis, plants rely heavily on external supports to acquire nitrogen. To this end, plants have adapted various strategies such as forming mutualistic relationships with nitrogen-fixing bacteria and evolving a large regulatory network that includes multiple transporters, sensors, and transcription factors for fine-tuning nitrate sensing and signaling. Nodule Inception (NIN) and NIN-like protein (NLP) are central in this network by executing multiple functions such as initiating and regulating the nodule symbiosis for nitrogen fixation, acting as the intracellular sensor to monitor the nitrate fluctuations in the environment, and activating the transcription of nitrate-responsive genes for optimal nitrogen uptake, assimilation, and usage. The involvement of NLPs in intracellular nitrate binding and early nitrate responses highlight their pivotal role in the primary nitrate response (PNR). Genome-wide reprogramming in response to nitrate by NLP is highly transient and rapid, requiring regulation in a precise and dynamic manner. This review aims to summarize recent progress in the study of NIN/NLP for a better understanding of the molecular basis of their roles and regulations in nitrate sensing and signaling, with the hope of shedding light on increasing biological nitrogen fixation and improving nitrogen use efficiency (NUE) to minimize fertilizer input in agriculture.

Generation and characterization of chimeric Tembusu viruses containing pre-membrane and envelope genes of Japanese encephalitis virus.

Since its outbreak in 2010, Tembusu virus (TMUV) has spread widely throughout China and Southeast Asia, causing significant economic losses to the poultry industry. In 2018, an attenuated vaccine called FX2010-180P (180P) was licensed for use in China. The 180P vaccine has demonstrated its immunogenicity and safety in mice and ducks. The potential use of 180P as a backbone for flavivirus vaccine development was explored by replacing the pre-membrane (prM) and envelope (E) genes of the 180P vaccine strain with those of Japanese encephalitis virus (JEV). Two chimeric viruses, 180P/JEV-prM-E and 180P/JEV-prM-ES156P with an additional E protein S156P mutation were successfully rescued and characterized. Growth kinetics studies showed that the two chimeric viruses replicated to similar titers as the parental 180P virus in cells. Animal studies also revealed that the virulence and neuroinvasiveness of the 180P/JEV-prM-E chimeric virus was decreased in mice inoculated intracerebrally (i.c.) and intranasally (i.n.), respectively, compared to the wild-type JEV strain. However, the chimeric 180P/JEV-prM-E virus was still more virulent than the parent 180P vaccine in mice. Additionally, the introduction of a single ES156P mutation in the chimeric virus 180P/JEV-prM-ES156P further attenuated the virus, which provided complete protection against challenge with a virulent JEV strain in the mouse model. These results indicated that the FX2010-180P could be used as a promising backbone for flavivirus vaccine development.