Association analysis of the sorting nexin 29 (SNX29) gene copy number variations with growth traits in Diannan small-ear (DSE) pigs.

SNX29 is a potential functional gene associated with meat production traits. Previous studies have shown that SNX29 copy number variation (CNV) could be implicated with phenotype in goats. However, in Diannan small-ear (DSE) pigs, the genetic impact of SNX29 CNV on growth traits remains unclear. Therefore, this study investigated the associations between SNX29 CNVs (CNV10810 and CNV10811) and growth traits in 415 DSE pigs. The results revealed that the CNV10810 mutation was significantly associated with backfat thickness in DSE pigs at 12 and 15 months old (P < 0.05), while the CNV10811 mutation had significant effects on various growth traits at 6 and 12 months old, particularly for body weight, body height, back height and backfat thickness (P < 0.05 or P < 0.001). In conclusion, our results confirm that SNX29 CNV plays a role in regulating growth and development in pigs, thus suggesting its potential application for pig breeding programmes.

Methylene Blue-Doped Carbonized Polymer Dots: A Potent Photooxygenation Scavenger Targeting Alzheimer's ß-Amyloid.

The abnormal aggregation of ß-amyloid protein (Aß) is one of the main pathological hallmarks of Alzheimer's disease (AD), and thus development of potent scavengers targeting Aß is considered an effective strategy for AD treatment. Herein, photosensitizer-doped carbonized polymer dots (PS-CPDs) were synthesized by a one-step hydrothermal method using photosensitizer (PS) and o-phenylenediamine (oPD) as precursors, and furtherly applied to inhibit Aß aggregation via photooxygenation. The inhibition efficiency of such PS-CPDs can be adjusted by varying the type of photosensitizer, and among them, methylene blue-doped carbonized polymer dots (MB-CPDs) showed the strongest photooxygenation inhibition capability. The results demonstrated that under 650 nm NIR light irradiation, MB-CPDs (2 µg/mL) produced reactive oxygen species (ROS) to efficiently inhibit Aß fibrillization and disaggregate mature Aß fibrils and increased the cultured cell viability from 50% to 83%. In vivo studies confirmed that MB-CPDs extended the lifespan of AD nematodes by 4 days. Notably, the inhibitory capability of MB-CPDs is much stronger than that of MB and previously reported carbonized polymer dots. This work indicated that potent photooxygenation carbon dots can be obtained by using a photosensitizer as one of the precursors, and the results have provided new insights into the design of potent photooxygenation carbon nanomaterials targeting Aß in AD treatment.

Efficacy and safety of acupuncture for pregnancy-related low back pain: A systematic review and meta-analysis.

Background: Pregnancy-related low back pain (PLBP) is a common musculoskeletal disorder, affecting people's physical and psychological health. Acupuncture is widely used in clinical practice as a treatment for PLBP. This study aimed to evaluate the efficacy and safety of acupuncture or acupuncture combined with other treatments for PLBP patients. Methods: The Cochrane Library, PubMed, EMBASE, Web of Science, the Chinese Biological Medicine Database, China National Knowledge Infrastructure, WanFang Database, and VIP information database were searched from inception to January 31, 2022. Randomized controlled trials (RCTs) were eligible, without blinding and language restriction. Cochrane's risk of bias tool was used to assess the methodological quality. Meta-analysis was performed using RevMan 5.3. Results: Twelve randomized controlled trials involving 1302 patients were included. The results showed that compared to the control group, the VAS score was significantly decreased after acupuncture treatment. In addition, no significant difference was found in the preterm delivery rate (RR = 0.38, 95%CI: 0.24 to 0.61, P = 0.97) after acupuncture treatment. Compared with other therapies, acupuncture or acupuncture plus other therapies revealed a significant increase in the effective rate (OR: 6.92, 95%CI: 2.44 to 19.67, I2 = 0%). No serious adverse events owing to acupuncture were reported. Conclusion: Acupuncture or acupuncture combined with other interventions was a safe and effective therapy for treating PLBP. However, the methodological quality of the RCTs was low. More rigorous and well-designed trials should be conducted.

Genome-Wide Association Analysis Identifies Genomic Regions and Candidate Genes for Growth and Fatness Traits in Diannan Small-Ear (DSE) Pigs.

In the livestock industry, the growth and fatness traits are directly related to production efficiency and economic profits. As for Diannan small-ear (DSE) pigs, a unique indigenous breed, the genetic architecture of growth and fatness traits is still elusive. The aim of this study was to search the genetic loci and candidate genes associated with phenotypic traits in DSE pigs using GWAS based on the Geneseek Porcine 50K SNP Chip data. A total of 22,146 single nucleotide polymorphisms (SNPs) were detected in 265 DSE pigs and used for Genome-wide association studies (GWAS) analysis. Seven SNPs were found to be associated with back height, chest circumference, cannon bone circumference, and backfat thickness at the suggestive significance level. Based on gene annotation results, these seven SNPs were, respectively, mapped to the following candidate genes, VIPR2, SLC10A2, NUCKS1, MCT1, CHCHD3, SMOX, and GPR1, which are mainly involved with adipocyte differentiation, lipid metabolism, skeletal muscle development, and average daily weight gain. Our work offers novel insights into the genetic architecture of economically important traits in swine and may play an important role in breeding using molecular markers in the DSE breed.

Epigallocatechin gallate-derived carbonized polymer dots: A multifunctional scavenger targeting Alzheimer's ß-amyloid plaques.

The design of high-efficiency scavengers targeting ß-amyloid protein (Aß) plaques in the progress of Alzheimer's disease (AD) has been recognized as an effective way to prevent and treat AD. Herein, epigallocatechin gallate (EGCG)-derived carbonized polymer dots (E-CPDs) were synthesized for the first time via a hydrothermal method using EGCG, an Aß inhibitor, as one of the raw materials. The inhibitory efficiency and fluorescent property of E-CPDs were elegantly modulated by adjusting the molar ratio of EGCG to nitrogen-containing dopant, o-phenylenediamine (oPD), and 75E-CPDs fabricated with 75 mM EGCG and 50 mM oPD showed the highest inhibitory capability. The multifunctionality of 75E-CPDs on inhibition of Aß fibrillization, Aß fibrils disaggregation, amyloid fluorescent detection, and intracellular reactive oxygen species scavenging was demonstrated. 75E-CPDs inhibited the formation of ß-sheet-rich Aß aggregates, alleviated Aß-induced cytotoxicity of cultured cells from 47% to 15%, and prolonged the lifespan of AD nematodes by scavenging in vivo amyloid plaques, demonstrating much higher performance than either EGCG or EGCG-free carbon dots. Notably, 75E-CPDs could rapidly disaggregate Aß fibrils on "second" scale, faster than any other disaggregating agents. The aromatic structure as well as hydroxyl and carboxyl groups existing on 75E-CPDs surface, which would interact with Aß species via hydrogen bonding, electrostatic interactions, and hydrophobic interactions, played critical roles in their inhibition and disaggregation capabilities. This work reveals that potent CDs can be fabricated by using an Aß inhibitor as the precursor, providing a new perspective for the design of multifunctional scavengers targeting amyloid plaques. STATEMENT OF SIGNIFICANCE: Alzheimer's disease (AD) is one of the top ten causes of death worldwide and seriously threatens human health. Recently, carbon nanomaterials have attracted much attention because of their good biocompatibility and capability in modulating Aß aggregation via multiple interactions. This work has for the first time fabricated epigallocatechin gallate-derived carbonized polymer dots (E-CPDs) and revealed the multifunctional potency of E-CPDs on alleviating the multifaced symptoms associated with ß-amyloid protein (Aß) fibrillization in the progression of AD. Notably, E-CPDs exhibited enhanced fluorescence emission upon binding to Aß fibrils, possessing potential as Aß fluorescent probes. It is believed that this work would open a new horizon in the design of multifunctional carbon nanomaterials as a potent amyloid scavenger for AD theranostics.

Effects of Genetic Variation of the Sorting Nexin 29 (SNX29) Gene on Growth Traits of Xiangdong Black Goat.

Previous studies have found that the copy number variation (CNV) and insertion/deletion (indels) located in the sorting nexin 29 (SNX29) gene, which is an important candidate gene related to meat production and quality, are associated with growth traits of African goats and Shaanbei white cashmere goats. However, the genetic effects of SNX29 genetic variation on growth traits of Xiangdong black (XDB) goat (a representative meat goat breed in China) are still unclear. The purpose of this study was to detect the mRNA expression level of SNX29 and to explore the genetic effects of CNV and indel within SNX29 on growth traits and gene expression in XDB goat. The SNX29 mRNA expression profile showed that the SNX29 was highly expressed in adipose tissues, indicating that the SNX29 gene could play a key role in subcutaneous adipose deposition of XDB goat. 17 bp indel (g.10559298-10559314), 21 bp indel (g.10918982-10919002) and CNV were detected in 516 individuals of XDB goat by PCR or qPCR. The association analysis of SNX29 CNV with growth traits in XDB goats showed that SNX29 CNV was significantly correlated with chest circumference and abdominal circumference (p < 0.01), and the normal type of SNX29 CNV goat individuals were more advantageous. For the mRNA expression of SNX29 gene, individuals with SNX29 copy number normal type had a higher trend than that of SNX29 gene with copy number gain type in longissimus dorsi muscle (p = 0.07), whereas individuals with SNX29 copy number gain type had a higher trend in abdominal adipose (p = 0.09). Overall, these results suggested that the SNX29 gene could play an important role in growth and development of XDB goats and could be used for marker-assisted selection (MAS) in XDB goats.

KAT2B Gene Polymorphisms Are Associated with Body Measure Traits in Four Chinese Cattle Breeds.

Identifying molecular markers related to growth characteristics or meat quality is significant for improving beef cattle breeds. K(lysine) acetyltransferase 2B (KAT2B) is a transcriptional co-activator regulating the acetylation modification of histones, which may be involved in the development and metabolism of muscle and adipose. However, investigations of KAT2B genetic variations in Chinese native cattle are still limited. This study aimed to identify crucial single nucleotide polymorphisms (SNPs) influencing the body measurements of Chinese native cattle. Biological evolution and conservation analysis showed that KAT2B was highly conserved among the ruminants. By qPCR assay, KAT2B gene expression was found to be spatiotemporally specific in bovine tissues such as adipose and liver. By the RFLP-PCR method, three SNPs of KAT2B (g.T61908C, g.T62131C, and g.C73406T) were identified in 827 individuals of four Chinese cattle breeds, including Qinchuan (n = 658), Fu (n = 52), Yak (n = 48), and Chaidam (n = 69) cattle. Association analysis between these KAT2B polymorphisms and the body measurements of Chinese native cattle revealed significant observations. The genetic effects of g.T61908C, g.T62131C, and g.C73406T on the associated phenotypes were illustrated in each breed. In Qinchuan cattle, g.T62131C was significantly associated with better body height, chest width, hip width, and withers height, for which TC and/or TT were the advantageous genotype. In Fu cattle, TT genotype of g.T61908C was associated to better body length, while individuals with TT or CC of g.T62131C showed higher circumference of cannon bone than those with TC genotype. In Yak, individuals with TT genotype of g.C73406T had heavier body weight. In Chaidam cattle, TC genotype of g.C73406T was associated to superior body weight, while CC genotype of g.C73406T was associated to superior chest girth and circumference of cannon bone. These findings suggest that KAT2B gene polymorphisms can be used as the molecular markers for the early molecular marker-assisted selection in beef cattle breeding programs.

A multi-target theranostic nano-composite against Alzheimer's disease fabricated by conjugating carbon dots and triple-functionalized human serum albumin.

The complex pathogenesis of Alzheimer's disease (AD) involves the aggregation and accumulation of amyloid ß-protein (Aß) as well as elevated levels of reactive oxygen species (ROS), which requires the development of comprehensive diagnostic and therapeutic interventions. In this work, a multifunctional theranostic nano-composite (HSA-BFP@CDs) is constructed by conjugating triple-functionalized human serum albumin (HSA-BFP) as a theranostic agent targeting Aß and carbon dots (CDs) as an ROS scavenger. HSA-BFP@CDs exhibits a fluorescence "off-on" effect at 700 nm upon interaction with Aß aggregates, showing the capability for detection of Aß plaques and potential for early diagnosis of AD. Besides, HSA-BFP@CDs effectively inhibits the aggregation of Aß, increasing the viability of Aß-treated cells from 74% to over 95% at 100 µg/mL. Moreover, multiple ROS, including hydroxyl radicals, superoxide radicals, hydrogen peroxide, and Aß-Cu2+-induced-ROS, can be scavenged by HSA-BFP@CDs, thus resulting in the mitigation of cellular oxidative damages. Experiments with the AD model of Caenorhabditis elegans further demonstrate the multifunctionality of HSA-BFP@CDs in imaging amyloid plaques, reducing Aß deposition, and relieving oxidative stress in vivo, showing the prospect for Aß- and ROS-targeted AD diagnosis and treatment. This work provided new insight into the design of protein-carbon dots conjugate and the development of multi-target therapy of AD. STATEMENT OF SIGNIFICANCE: Alzheimer's disease (AD) is the most common form of dementia, which currently affects over 55 million people worldwide. Due to the complex pathogenesis of AD involving amyloid ß-protein (Aß) aggregation as well as elevated levels of reactive oxygen species (ROS), it is highly desired to develop comprehensive diagnostic and therapeutic interventions. In this paper, we fabricated a multifunctional theranostic nano-composite (HSA-BFP@CDs) via the conjugation of triple-functionalized human serum albumin (HSA-BFP) and carbon dots (CDs). The multifunctionality of HSA-BFP@CDs for efficient detection of Aß aggregates and inhibition of Aß aggregation as well as scavenging of ROS was demonstrated, demonstrating the potential of the protein-carbon dots conjugate for the multi-target therapy of AD.

L-type calcium channel blockers decrease the iron overload-mediated oxidative stress in renal epithelial cells by reducing iron accumulation.

Iron-mediated oxidative stress has been recognized as one of the leading causes of chronic kidney injury. The effect of L-type calcium channel (LTCC) blocker on iron overload has been shown in cardiomyocytes, liver cells, and nerve cells. So far, few studies have examined whether blockers improve kidney iron-mediated oxidative stress. Yet, the precise mechanism through which blockers regulate kidney iron transport still remains unclear. In the present work, treatment with nifedipine or verapamil decreased oxidative stress and reduced the cell apoptosis-induced by ferric ammonium citrate (P < 0.05), decreased cellular iron contents, and prevented the rising of iron level-induced by ferric ammonium citrate (P > 0.05) in HK-2 and HEK293 cells. Besides, nifedipine and verapamil treatments increased the expression of divalent metal transporter 1, divalent metal transporter ZIP14, and ferroportin1 in HK-2 cells and increased ferroportin1 expression in HEK293 cells. In summary, LTCC blockers alleviate iron overload-induced oxidative stress in renal epithelial cells by blocking the iron uptake and enhancing cellular iron transport and/or iron export, thus synergistically reducing the cellular iron accumulation. Consequently, LTCC blockers may be used as a novel treatment for the prevention of primary or secondary iron overload-kidney injury.

Loading Auristatin PE onto boron nitride nanotubes and their effects on the apoptosis of Hep G2 cells.

Auristatin PE (PE) as an anti-microtubule agent possesses good anticancer activity. However, the poor target effect and strong side effect limit the clinical application of PE. Boron nitride nanotubes (BNNTs) represent an outstanding carrier candidate providing a wise choice for liver-targeted drug delivery. A drug delivery system based on BNNTs and PE (BNNTs-PE) against liver cancer cells was designed and constructed in this study. Firstly, BNNTs were prepared and hydroxylated, subsequently, PE was loaded onto BNNTs by noncovalent conjugation and was stable at neutral pH but released at pH 4.49. It was found that BNNTs-PE demonstrates an enhanced anticancer activity against Hep G2 cells in comparison with free PE. BNNTs-PE kills cancer cells in a manner of mitochondria-mediated apoptosis pathway through reducing the mitochondrial membrane potential, activating caspase cascade. This BNNTs-PE system may be very promising for the treatment of liver cancer in the future.

Quercetin Improves Glucose and Lipid Metabolism of Diabetic Rats: Involvement of Akt Signaling and SIRT1.

Glucose and lipid metabolism disorder in diabetes mellitus often causes damage to multiple tissues and organs. Diabetes mellitus is beneficially affected by quercetin. However, its concrete mechanisms are yet to be fully elucidated. In our study, diabetes was induced in Sprague-Dawley rats by STZ injection. The rats were randomly divided into normal control, diabetic model, low-dose quercetin treatment, high-dose quercetin treatment, and pioglitazone treatment groups. Fasting blood glucose was collected to evaluate diabetes. Immunohistochemistry and fluorometric assay were performed to explore SIRT1. Akt levels were measured through immunoprecipitation and Western blot. After 12 weeks of quercetin treatment, the biochemical parameters of glucose and lipid metabolism improved to varying degrees. Hepatic histomorphological injury was alleviated, and hepatic glycogen content was increased. The expression and activity of hepatic SIRT1 were enhanced, and Akt was activated by phosphorylation and deacetylation. These results suggested that the beneficial effects of quercetin on glucose and lipid metabolism disorder are probably associated with the upregulated activity and protein level of SIRT1 and its influence on Akt signaling pathway. Hence, quercetin shows potential for the treatment of glucose and lipid metabolism disorder in diabetes mellitus.