Differential expression of microRNAs in serum exosomes of obese and non-obese mice and analysis of their function.

OBJECTIVE: To extract exosomes from obese and non-obese mice, screen specifically expressed microRNAs by high-throughput sequencing and explore their roles. METHODS: An animal obesity model was constructed, and the successful construction of the obesity model was verified by HE staining, Western Blot and RT-qPCR. In addition, exosomes were extracted and verified by Western Blot. High-throughput sequencing was performed on the extracted serum exosomes to screen for differentially expressed microRNAs. fluorescence quantitative RT-PCR (RT-qPCR) was used to validate the differentially expressed miRNAs and explore their functions. RESULTS: 8 microRNAs were up-regulated and 11 microRNAs were down-regulated. mmu-miR-674-5p and X_28316 were significantly down-regulated and had the greatest impact on protein pathways. 8_13258 was significantly up-regulated and affected multiple protein pathways. GO enrichment analysis suggested that the differentially expressed microRNAs were mainly involved in the cleavage of microtubule activity, transferase activity/transferase pentameric acid. GO enrichment analysis suggested that differentially expressed microRNAs were mainly involved in the processes of cleavage microtubule activity, transferase activity/transfer pentamer, and threonine phosphatase/threonine kinase activity.KEGG pathway enrichment analysis showed that differentially expressed microRNAs were mainly involved in the processes of regulating the phosphorylation of TP53 activity, the G2/M DNA damage checkpoint, and the processing of the ends of DNA double-strand breaks. Protein interaction networks were enriched for Stat3, Fgr, Camk2b, Rac1, Asb6, and Ankfy1. Suggesting that they may be mediated by differential genes to participate in the process of insulin resistance. qRT-PCR results showed that the expression trend of mmu-miR-674-5p was consistent with the sequencing results. It suggests that it may be able to participate in the regulation of insulin resistance as a target gene. CONCLUSION: microRNAs were differentially expressed in serum exosomes of obese and non-obese mice and might be involved in the specific regulation of insulin resistance. mmu-miR-674-5p was differentially expressed significantly and the validation trend was consistent with it, suggesting that it might be able to participate in the regulation of insulin resistance as a target gene.

The mediating role of synovitis in meniscus pathology and knee osteoarthritis radiographic progression.

Meniscus pathologies (damage, extrusion) and synovitis are associated with knee osteoarthritis (KOA); however, whether synovitis mediates the relationship between meniscus pathologies and KOA radiographic progression remains unclear. We conducted an observational study in the Osteoarthritis Initiative (OAI) cohort, with a 48-month follow-up. Meniscus pathology and synovitis were measured by MRI osteoarthritis knee score (MOAKS) at baseline and 24 months, and a comprehensive synovitis score was calculated using effusion and Hoffa synovitis scores. The knee osteoarthritis radiographic progression was considered that Kellgren-Lawrence (KL) grade and joint space narrowing (JSN) grade at 48 months were increased compared to those at baseline. This study included a total of 589 participants, with KL grades mainly being KL1 (26.5%), KL2 (34.1%), and KL3 (30.2%) at baseline, while JSN grades were mostly 0 at baseline. A logistic regression model was used to analyze the relationship between meniscus pathology, synovitis, and KOA progression. Mediation analysis was used to evaluate the mediation effect of synovitis. The average age of the participants was 61 years old, 62% of which were female. The medial meniscus extrusion was longitudinally correlated with the progression of KL (odds ratio [OR]: 2.271, 95% confidence interval [CI]: 1.412-3.694) and medial JSN (OR: 3.211, 95% CI: 2.040-5.054). Additionally, the longitudinal correlation between medial meniscus damage and progression of KOA (OR: 1.853, 95% CI: 1.177-2.941) and medial JSN (OR: 1.655, 95% CI: 1.053-2.602) was significant. Synovitis was found to mediate the relationship between medial meniscus extrusion and KL and medial JSN progression at baseline (ß: 0.029, 95% CI: 0.010-0.053; ß: 0.022, 95% CI: 0.005-0.046) and beyond 24 months (ß: 0.039, 95% CI: 0.016-0.068; ß: 0.047, 95% CI: 0.020-0.078). However, we did not find evidence of synovitis mediating the relationship between meniscal damage and KOA progression. Synovitis mediates the relationship between medial meniscus extrusion (rather than meniscus damage) and KOA progression.

Compound heterozygous mutation of the SNX14 gene causes autosomal recessive spinocerebellar ataxia 20.

Objective: The article aims to provide genetic counseling to a family with two children who were experiencing growth and developmental delays. Methods: Clinical information of the proband was collected. Peripheral blood was collected from core family members to identify the initial reason for growth and developmental delays by whole exome sequencing (WES) and Sanger sequencing. To ascertain the consequences of the newly discovered variants, details of the variants detected were analyzed by bioinformatic tools. Furthermore, we performed in vitro experimentation targeting SNX14 gene expression to confirm whether the variants could alter the expression of SNX14. Results: The proband had prenatal ultrasound findings that included flattened frontal bones, increased interocular distance, widened bilateral cerebral sulci, and shortened long bones, which resulted in subsequent postnatal developmental delays. The older sister also displayed growth developmental delays and poor muscle tone. WES identified compound heterozygous variants of c.712A>T (p.Arg238Ter) and .2744A>T (p.Gln915Leu) in the SNX14 gene in these two children. Both are novel missense variant that originates from the father and mother, respectively. Sanger sequencing confirmed this result. Following the guideline of the American College of Medical Genetics and Genomics (ACMG), the SNX14 c.712A>T (p.Arg238Ter) variant was predicted to be pathogenic (P), while the SNX14 c.2744A>T (p.Gln915Leu) variant was predicted to be a variant of uncertain significance (VUS). The structural analysis revealed that the c.2744A>T (p.Gln915Leu) variant may impact the stability of the SNX14 protein. In vitro experiments demonstrated that both variants reduced SNX14 expression. Conclusion: The SNX14 gene c.712A>T (p.Arg238Ter) and c.2744A>T (p.Gln915Leu) were identified as the genetic causes of growth and developmental delay in two affected children. This conclusion was based on the clinical presentations of the children, structural analysis of the mutant protein, and in vitro experimental validation. This discovery expands the range of SNX14 gene variants and provides a foundation for genetic counseling and guidance for future pregnancies in the affected children's families.

Highly Efficient One-pot Electrosynthesis of Oxime Ethers from NOx over Ultrafine MgO Nanoparticles Derived from Mg-based Metal-Organic Frameworks.

Oxime ethers are attractive compounds in medicinal scaffolds due to the biological and pharmaceutical properties, however, the crucial and widespread step of industrial oxime formation using explosive hydroxylamine (NH2OH) is insecure and troublesome. Herein, we present a convenient method of oxime ether synthesis in a one-pot tandem electrochemical system using magnesium based metal-organic framework-derived magnesium oxide anchoring in self-supporting carbon nanofiber membrane catalyst (MgO-SCM), the in situ produced NH2OH from nitrogen oxides electrocatalytic reduction coupled with aldehyde to produce 4-cyanobenzaldoxime with a selectivity of 93 % and Faraday efficiency up to 65.1 %, which further reacted with benzyl bromide to directly give oxime ether precipitate with a purity of 97 % by convenient filtering separation. The high efficiency was attributed to the ultrafine MgO nanoparticles in MgO-SCM, effectively inhibiting hydrogen evolution reaction and accelerating the production of NH2OH, which rapidly attacked carbonyl of aldehydes to form oximes, but hardly crossed the hydrogenation barrier of forming amines, thus leading to a high yield of oxime ether when coupling benzyl bromide nucleophilic reaction. This work highlights the importance of kinetic control in complex electrosynthetic organonitrogen system and demonstrates a green and safe alternative method for synthesis of organic nitrogen drug molecules.

Identification of chromosomal abnormalities in miscarriages by CNV-Seq.

OBJECTIVE: The primary object of this study is to analyze chromosomal abnormalities in miscarriages detected by copy number variants sequencing (CNV-Seq), establish potential pathways or genes related to miscarriages, and provide guidance for birth health in the following pregnancies. METHODS: This study enrolled 580 miscarriage cases with paired clinical information and chromosomal detection results analyzed by CNV-Seq. Further bioinformatic analyses were performed on validated pathogenic CNVs (pCNVs). RESULTS: Of 580 miscarriage cases, three were excluded as maternal cell contamination, 357 cases showed abnormal chromosomal results, and the remaining 220 were normal, with a positive detection rate of 61.87% (357/577). In the 357 miscarriage cases, 470 variants were discovered, of which 65.32% (307/470) were pathogenic. Among all variants detected, 251 were numerical chromosomal abnormalities, and 219 were structural abnormalities. With advanced maternal age, the proportion of numerical abnormalities increased, but the proportion of structural abnormalities decreased. Kyoto Encyclopedia of Genes and Genomes pathway and gene ontology analysis revealed that eleven pathways and 636 biological processes were enriched in pCNVs region genes. Protein-protein interaction analysis of 226 dosage-sensitive genes showed that TP53, CTNNB1, UBE3A, EP300, SOX2, ATM, and MECP2 might be significant in the development of miscarriages. CONCLUSION: Our study provides evidence that chromosomal abnormalities contribute to miscarriages, and emphasizes the significance of microdeletions or duplications in causing miscarriages apart from numerical abnormalities. Essential genes found in pCNVs regions may account for miscarriages which need further validation.

Electrocatalytic Systems for NOx Valorization in Organonitrogen Synthesis.

Inorganic nitrogen oxide (NOx ) species, such as NO, NO2 , NO3 - , NO2 - generated from the decomposition of organic matters, volcanic eruptions and lightning activated nitrogen, play important roles in the nitrogen cycle system and exploring the origin of life. Meanwhile, excessive emission of NOx gases and residues from industry and transportation causes troubling problems to the environment and human health. How to efficiently handle these wastes is a global problem. In response to the growing demand for sustainability, scientists are actively pursuing sustainable electrochemical technologies powered by renewable energy sources and efficient utilization of hydrogen energy to convert NOx species into high-value organonitrogen chemicals. In this minireview, recent advances of electrocatalytic systems for NOx species valorization in organonitrogen synthesis are classified and described, such as amino acids, amide, urea, oximes, nitrile etc., that have been widely applied in medicine, life science and agriculture. Additionally, the current challenges including multiple side reactions and complicated paths, viable solutions along with future directions ahead in this field are also proposed. The coupling electrocatalytic systems provide a green mode for fixing nitrogen cycle bacteria and bring enlightenment to human sustainable development.

In Situ Deposition of Drug and Gene Nanoparticles on a Patterned Supramolecular Hydrogel to Construct a Directionally Osteochondral Plug.

The integrated repair of bone and cartilage boasts advantages for osteochondral restoration such as a long-term repair effect and less deterioration compared to repairing cartilage alone. Constructing multifactorial, spatially oriented scaffolds to stimulate osteochondral regeneration, has immense significance. Herein, targeted drugs, namely kartogenin@polydopamine (KGN@PDA) nanoparticles for cartilage repair and miRNA@calcium phosphate (miRNA@CaP) NPs for bone regeneration, were in situ deposited on a patterned supramolecular-assembled 2-ureido-4 [lH]-pyrimidinone (UPy) modified gelation hydrogel film, facilitated by the dynamic and responsive coordination and complexation of metal ions and their ligands. This hydrogel film can be rolled into a cylindrical plug, mimicking the Haversian canal structure of natural bone. The resultant hydrogel demonstrates stable mechanical properties, a self-healing ability, a high capability for reactive oxygen species capture, and controlled release of KGN and miR-26a. In vitro, KGN@PDA and miRNA@CaP promote chondrogenic and osteogenic differentiation of mesenchymal stem cells via the JNK/RUNX1 and GSK-3ß/ß-catenin pathways, respectively. In vivo, the osteochondral plug exhibits optimal subchondral bone and cartilage regeneration, evidenced by a significant increase in glycosaminoglycan and collagen accumulation in specific zones, along with the successful integration of neocartilage with subchondral bone. This biomaterial delivery approach represents a significant toward improved osteochondral repair.

Electrocatalytic Synthesis of Pyridine Oximes using in Situ Generated NH2 OH from NO species on Nanofiber Membranes Derived from NH2 -MIL-53(Al).

Pyridine oximes produced from aldehyde or ketone with hydroxylamine (NH2 OH) have been widely applied in pharmaceutics, enzymatic and sterilization. However, the important raw material NH2 OH exhibits corrosive and unstable properties, leading to substantial energy consumption during storage and transportation. Herein, this work presents a novel method for directly synthesizing highly valuable pyridine oximes using in situ generated NH2 OH from electrocatalytic NO reduction with well-design nanofiber membranes (Al-NFM) derived from NH2 -MIL-53(Al). Particularly, 2-pyridinealdoxime, the precursor of antidote pralidoxime (2-PAM) for nerve agents suffering from scarcity and high cost, was achieved with a Faraday efficiency up to 49.8 % and a yield of 92.1 %, attributing to the high selectivity of NH2 OH production on Al-NFM, further easily reacted with iodomethane to produce 2-PAM. This study proposes a creative approach, having wide universality for synthesizing pyridine and other oximes with a range of functional groups, which not only facilitates the conversion of exhaust gas (NO) and waste water (NO2 - ) into valuable chemicals especially NH2 OH production and in situ utilization through electrochemistry, but also holds significant potential for synthesis of neuro detoxifying drugs to humanity security.

Walnut (Juglans regia L.) Oligopeptides Alleviate Alcohol-Induced Acute Liver Injury through the Inhibition of Inflammation and Oxidative Stress in Rats.

The study was aimed at investigating the effects of walnut oligopeptides (WOPs) on alcohol-induced acute liver injury and its underlying mechanisms. Male Sprague Dawley (SD) rats were randomly assigned to six groups: normal control, alcohol control, whey protein (440 mg/kg.bw), and three WOPs (220 mg/kg.bw, 440 mg/kg.bw, 880 mg/kg.bw) groups. After 30 days of gavage, ethanol with a volume fraction of 50%, administered at a dose of 7 g/kg.bw., caused acute liver injury. A righting reflex experiment and a blood ethanol concentration evaluation were then performed. Serum biochemical parameters, inflammatory cytokines, liver alcohol metabolism enzymes, oxidative stress biomarkers, liver nuclear factor-κB (NF-κB p65), and cytochrome P4502E1 expression were determined. The results revealed that the intervention of 440 mg/kg and 880 mg/kg WOPs could alleviate the degree of intoxication, decrease blood ethanol concentration, alleviate alcohol-induced hepatic steatosis, enhance the activity of hepatic ethanol metabolizing enzymes and antioxidant capacity, reduce lipid oxidation products and pro-inflammatory factor contents, and inhibit the expression of NF-κBp65 in the livers of rats. The outcomes of the study suggest that WOPs have beneficial effects on liver damage caused by acute ethanol binge drinking, with the high-dose WOPs (880 mg/kg.bw) exerting the most pronounced hepatoprotective effect.

Recent Advances in Co3O4-Based Composites: Synthesis and Application in Combustion of Methane.

In recent years, it has been found that adjusting the organizational structure of Co3O4 through solid solution and other methods can effectively improve its catalytic performance for the oxidation of low concentration methane. Its catalytic activity is close to that of metal Pd, which is expected to replace costly noble metal catalysts. Therefore, the in-depth research on the mechanism and methods of Co3O4 microstructure regulation has very important academic value and economic benefits. In this paper, we reviewed the catalytic oxidation mechanism, microstructure regulation mechanism, and methods of nano-Co3O4 on methane gas, which provides reference for the development of high-activity Co3O4-based methane combustion catalysts. Through literature investigation, it is found that the surface energy state of nano-Co3O4 can be adjusted by loading of noble metals, resulting in the reduction of Co-O bond strength, thus accelerating the formation of reactive oxygen species chemical bonds, and improving its catalytic effect. Secondly, the use of metal oxides and non-metallic oxide carriers helps to disperse and stabilize cobalt ions, improve the structural elasticity of Co3O4, and ultimately improve its catalytic performance. In addition, the performance of the catalyst can be improved by adjusting the microstructure of the composite catalyst and optimizing the preparation process. In this review, we summarize the catalytic mechanism and microstructure regulation of nano-Co3O4 and its composite catalysts (embedded with noble metals or combined with metallic and nonmetallic oxides) for methane combustion. Notably, this review delves into the substance of measures that can be used to improve the catalytic performance of Co3O4, highlighting the constructive role of components in composite catalysts that can improve the catalytic capacity of Co3O4. Firstly, the research status of Co3O4 composite catalyst is reviewed in this paper. It is hoped that relevant researchers can get inspiration from this paper and develop high-activity Co3O4-based methane combustion catalyst.

Evaluation of the prognostic value of the anatomical characteristics of the bony structures in the shoulder in bursal-sided partial-thickness rotator cuff tears.

Background: In recent studies, individual scapular anatomy has been found to be related to degenerative full-thickness rotator cuff tears. However, research on the relationship between the anatomical characteristics of shoulder radiographs and bursal-sided partial-thickness rotator cuff tears (PTRCTs) is limited, and the risk factors for this pathology still need to be determined. Methods: The bursal-sided PTRCTs group included 102 patients without a history of shoulder trauma who underwent arthroscopy between January 2021 and October 2022. A total of 102 demographically matched outpatients with intact rotator cuffs were selected as the control group. Radiographs were used to measure the lateral acromial angle (LAA), critical shoulder angle (CSA), greater tuberosity angle (GTA), ß-angle, acromion index (AI), acromiohumeral distance (AHD), acromial tilt (AT), acromial slope (AS), acromial type, and acromial spur by two independent observers. Multivariate analyses of these data were used to identify potential risk factors for bursal-sided PTRCTs. Receiver operating characteristic (ROC) analysis was performed to assess the sensitivity and specificity of CSA, GTA, and AI for this type of pathology. Result: The ß-angle, AHD, AS and acromion type showed no difference between bursal-sided PTRCTs and controls (p = 0.009, 0.200, 0.747 and 0.078, respectively). CSA, GTA and AI were significantly higher in bursal-sided PTRCTs (p < 0.001). LAA, ß-angle and AT were significantly lower in bursal-sided PTRCTs. Multivariate logistic regression analysis demonstrated significant correlations between the acromial spur (p = 0.024), GTA (p = 0.004), CSA (p = 0.003) and AI (p = 0.048) and bursal-sided PTRCTs. The areas under the ROC curves for AI, CSA, and GTA were 0.655 (95% CI 0.580-0.729), 0.714 (95% CI 0.644-0.784), and 0.695 (95% CI 0.622-0.767), respectively. Conclusion: Acromial spur, GTA, CSA, and AI were independent risk factors for bursal-sided PTRCTs. Furthermore, CSA was the most powerful predictor of bursal-sided PTRCTs compared to GTA and AI.

The Protective Effect of Walnut Oligopeptides against Indomethacin-Induced Gastric Ulcer in Rats.

The aim of this study was to investigate the potential protective effects of walnut oligopeptides (WOPs) on indomethacin-induced gastric ulcers in rats. The rats were divided into the following groups: normal group, model group, omeprazole group (0.02 g/kg), and WOPs groups (0.22, 0.44, and 0.88 g/kg, respectively). After receiving gavage once per day for 30 consecutive days, the rats were injected intraperitoneally with indomethacin 48 mg/kg to induce gastric ulcers. Then, the serum inflammatory cytokines and gastric prostaglandin E2 (PGE2), oxidative stress-related indicators, and the RNA expression of COX-1 and COX-2 were measured. The results revealed that WOPs confer significant gastroprotection on gastric ulcers caused by indomethacin, regulating inflammatory cytokines, oxidative stress, and prostaglandins synthesis, and enhancing the expression of COX-1 and COX-2 in gastric tissue, thus exerting its protective effect on gastric mucosa. The gastroprotective mechanism may be related to the involvement of the arachidonic acid metabolism and upregulation of tryptophan, phenylalanine, tyrosine, and alpha-Linolenic acid metabolism synthesis in vivo.

The Effects of Peanut Oligopeptides on Exercise-Induced Fatigue in Mice and Its Underlying Mechanism.

The aim of this study was to clarify the anti-fatigue effect of peanut oligopeptides (POPs) in mice and to investigate its possible underlying mechanism. A total of 150 male ICR mice were randomly assigned into five groups: control, whey protein (0.50 g/kg·bw), and three peanut peptide groups (0.25, 0.50, and 1.00 g/kg·bw). All the mice were treated with intra-gastric administration for 30 days. Following the intervention, a weight-loaded swimming test, blood lactate concentration, glycogen content, the activities of antioxidant factors and energy metabolism enzymes, and the function of mitochondria in the skeletal muscle were examined. The results show that POP intervention significantly prolonged the exhaustive swimming time, decreased blood lactate concentration levels, regulated the process of energy metabolism, and increased the level of antioxidant enzymes, muscle glycogen, and expressions of mtTFA and NRF-1 in the mitochondria of the gastrocnemius muscle. The results suggest that POPs produce an anti-fatigue effect in the animals, and they may exert this effect through the mechanism of improving the animals' antioxidant capacity to reduce oxidative damage levels and regulating the process of energy metabolism.

Locking Effect in Metal@MOF with Superior Stability for Highly Chemoselective Catalysis.

Ultrasmall metal nanoparticles (NPs) show high catalytic activity in heterogeneous catalysis but are prone to reunion and loss during the catalytic process, resulting in low chemoselectivity and poor efficiency. Herein, a locking effect strategy is proposed to synthesize high-loading and ultrafine metal NPs in metal-organic frameworks (MOFs) for efficient chemoselective catalysis with high stability. Briefly, the MOF ZIF-90 with aldehyde groups cooperating with diamine chains via aldimine condensation was interlocked, which was employed to confine in situ formation of Au NPs, denoted as Au@L-ZIF-90. The optimized Au@La-ZIF-90 has highly dispersed Au NPs (2.60 ± 0.81 nm) with a loading amount around 22 wt % and shows a great performance toward 3-aminophenylacetylene (3-APA) from the selective hydrogenation of 3-nitrophenylacetylene (3-NPA) with a high yield (99%) and excellent durability (over 20 cycles), far superior to contrast catalysts without chains locking and other reported catalysts. In addition, experimental characterization and systematic density functional theory calculations further demonstrate that the locked MOF modulates the charge of Au nanoparticles, making them highly specific for nitro group hydrogenation to obtain 3-APA with high selectivity (99%). Furthermore, this locking effect strategy is also applicable to other metal nanoparticles confined in a variety of MOFs, and all of these catalysts locked with chains show great selectivity (≥90%) of 3-APA. The proposed strategy in this work provides a novel and universal method for precise control of the inherent activity of accessible metal nanoparticles with a programmable MOF microenvironment toward highly specific catalysis.

Rejuvenation of tendon stem/progenitor cells for functional tendon regeneration through platelet-derived exosomes loaded with recombinant Yap1.

The regenerative capabilities including self-renewal, migration and differentiation potentials shift from the embryonic phase to the mature period of endogenous tendon stem/progenitor cells (TSPCs) characterize restricted functions and disabilities following tendon injuries. Recent studies have shown that tendon regeneration and repair rely on multiple specific transcription factors to maintain TSPCs characteristics and functions. Here, we demonstrate Yap, a Hippo pathway downstream effector, is associated with TSPCs phenotype and regenerative potentials through gene expression analysis of tendon development and repair process. Exosomes have been proven an efficient transport platform for drug delivery. In this study, purified exosomes derived from donor platelets are loaded with recombinant Yap1 protein (PLT-Exo-Yap1) via electroporation to promote the stemness and differentiation potentials of TSPCs in vitro. Programmed TSPCs with Yap1 import maintain stemness and functions after long-term passage in vitro. The increased oxidative stress levels of TSPCs are related to the phenotype changes in duplicative senescent processes. The results show that treatment with PLT-Exo-Yap1 significantly protects TSPCs against oxidative stressor-induced stemness loss and senescence-associated secretory phenotype (SASP) through the NF-κB signaling pathway. In addition, we fabricate an Exos-Yap1-functioned GelMA hydrogel with a parallel-aligned substrate structure to enhance TSPCs adhesion, promote cell stemness and force regenerative cells toward the tendon lineage for in vitro and in vivo tendon regeneration. The application of Exos-Yap1 functioned implant assists new tendon-like tissue formation with good mechanical properties and locomotor functions in a full-cut Achilles tendon defect model. Thus, PLT-Exo-Yap1-functionalized GelMA promotes the rejuvenation of TSPCs to facilitate functional tendon regeneration. STATEMENT OF SIGNIFICANCE: This is the first study to explore that the hippo pathway downstream effector Yap is involved in tendon aging and repair processes, and is associated with the regenerative capabilities of TSPCs. In this syudy, Platelet-derived exosomes (PLT-Exos) act as an appropriate carrier platform for the delivery of recombinant Yap1 into TSPCs to regulate Yap activity. Effective Yap1 delivery inhibit oxidative stress-induced senescence associated phenotype of TSPCs by blocking ROS-mediated NF-κb signaling pathway activation. This study emphasizes that combined application of biomimetic scaffolds and Yap1 loaded PLT-Exos can provide structural support and promote rejuvenation of resident cells to assist functional regeneration for Achilles tendon defect, and has the prospect of clinical setting.

ZnO nanoparticle modified chitosan/borosilicate bioglass composite scaffold for inhibiting bacterial infection and promoting bone regeneration.

The treatment of implant-associated bone infection remains a significant clinical challenge. However, bone scaffolds with antimicrobial activity and osteoinductive properties can prevent these infections and improve clinical outcomes. In this study, borosilicate bioglass and chitosan composite scaffolds were prepared, and then the surface was modified with nano-zinc oxide.In vitroandin vivoexperiments showed that the chitosan/borosilicate bioglass scaffolds have good degradation and osteogenic properties, while the oxidized Zinc scaffolds have better antibacterial properties.

Inert metal induces the modulation of unsaturated aldehyde absorption mode for enhanced selective hydrogenation.

Selective hydrogenation of α,ß-unsaturated aldehydes to obtain a high yield of unsaturated alcohols is important in industrial production. This is still a great challenge because it is thermally more favorable for the hydrogenation of CC than for the CO bond. Various strategies have been developed to optimize the catalysts for improving selectivity but are usually accompanied by the sacrifice of catalytic activity. Herein, we adopt the inert metal inducement strategy to synthesize a series of Ir-M alloy nanoparticle catalysts. The optimal catalyst IrCd5 exhibits impressive catalytic performance in the selective hydrogenation of cinnamaldehyde, achieving 96.7% conversion with 94.3% selectivity for cinnamal alcohol, which is far superior to that of the Ir counterpart. Furthermore, the H2 temperature-programmed desorption (H2-TPD) test, styrene-TPD test, surface valence band test and density functional theory calculations demonstrate that the adsorption mode of cinnamaldehyde shifted from parallel to vertical configurations after introducing an inert metal. Compared to Ir, the weaker adsorption of alkene and stronger adsorption of the substrate for IrCd5 lead to the prior adsorption and hydrogenation of the CO bond, thus elevating the selectivity of the cinnamal alcohol. This strategy disperses precious metal nanoparticles effectively, maximizes atomic utilization, and improves the selectivity, which provides a new avenue to design bimetal alloy catalysts for the selective hydrogenation of α,ß-unsaturated aldehydes.

Association of low birthweight and small for gestational age with maternal ferritin levels: A retrospective cohort study in China.

Background: Birthweight have profound impacts on health status throughout lifetime, however, the relationship between maternal ferritin level in pregnancy and birthweight of the newborn remains controversial. Objective: This retrospective cohort research was to analyze the association between maternal ferritin levels during pregnancy with birthweight outcomes, primarily for low birthweight (LBW) and small for gestational age (SGA). Methods: Newborns weighing lower than 2,500 grams were defined as LBW. SGA is defined as birthweight lower than the 10th percentile of the distribution of newborns' birthweight of the same gestational age. Multivariable logistic regressions have been used to explore the association of maternal ferritin levels and birthweight related outcomes, in which the ferritin concentration was logarithm transformed in the model. We further used restricted cubic spline models to explore linear/non-linear dose-response manners of ferritin level and birthweight outcomes. Results: A total of 3,566 pregnant women were included in the study. In the results of the present study, we observed that maternal ferritin levels were linearly associated with the risk of LBW (p-trend = 0.005) and SGA (p-trend = 0.04), with the adjusted odds ratios (ORs) of 1.78 (95% CI 1.37-2.32) for LBW and 1.87 (95% CI 1.38-2.54) for SGA with an increase in Ln-ferritin concentrations per unit. The adjusted ORs across quartiles of ferritin levels were 2.14 (95% CI 1.03-4.47) for Quartile 2, 3.13 (95% CI 1.47-6.69) for Quartile 3, and 3.63 (95% CI 1.52-8.68) for Quartile 4 for LBW. The adjusted ORs of LBW and SGA among women using supplemental iron were 0.56 (95% CI 0.38, 0.85) and 0.65 (95% CI 0.40, 1.05) compared with non-users, respectively. Conclusions: Our findings found a linear dose-response relationship between ferritin levels and an increased risk of poor birthweight outcomes, suggesting that maternal ferritin level during pregnancy may provide an additional predictor for differentiating poor birthweight related outcomes. Further exploration should be conducted to ensure maternal ferritin thresholds and iron supplement doses.

Colorectal cancer organoid models uncover oxaliplatin-resistant mechanisms at single cell resolution.

PURPOSE: Oxaliplatin-based chemotherapy is a standard treatment for advanced colorectal cancer (CRC) patients. However, chemoresistance-induced resistance is an essential cause for mortality. Therefore, it is necessary to study the mechanism of drug resistance in CRC. METHODS: Here, we established two strains of patient-derived organoids (PDOs) selected from oxaliplatin-resistant and treatment-naïve CRC patients. To dissect the drug-resistant mechanisms, these CRC-PDOs were subjected to single-cell RNA sequencing (scRNA-Seq). RESULTS: We found that the drug sensitivity test outcome from these organoids subjected to oxaliplatin and 5-FU exposure was consistent with the clinic readout. CRC-PDOs well recapitulated the morphology and histology of their parental biopsies based on HE and IHC staining of pathological biomarkers. The scRNA-Seq data filtered drug-resistant cell populations and related signaling pathways (e.g. oxidative phosphorylation and ATP metabolic process). The data also revealed several putative drug resistant-driven genes (STMN1, VEGFA and NDRG1) and transcription factors (E2F1, BRCA1, MYBL2, CDX2 and CDX1). CONCLUSION: We generated an oxaliplatin-resistant CRC organoid model that was employed to provide potential therapeutic targets for treating CRC patients exhibiting oxaliplatin-resistance.