Bacterial capsules: Occurrence, mechanism, and function.

In environments characterized by extended multi-stress conditions, pathogens develop a variety of immune escape mechanisms to enhance their ability to infect the host. The capsules, polymers that bacteria secrete near their cell wall, participates in numerous bacterial life processes and plays a crucial role in resisting host immune attacks and adapting to their niche. Here, we discuss the relationship between capsules and bacterial virulence, summarizing the molecular mechanisms of capsular regulation and pathogenesis to provide new insights into the research on the pathogenesis of pathogenic bacteria.

Cooperation of quorum sensing and central carbon metabolism in the pathogenesis of Gram-positive bacteria.

Quorum sensing (QS), an integral component of bacterial communication, is essential in coordinating the collective response of diverse bacterial pathogens. Central carbon metabolism (CCM), serving as the primary metabolic hub for substances such as sugars, lipids, and amino acids, plays a crucial role in the life cycle of bacteria. Pathogenic bacteria often utilize CCM to regulate population metabolism and enhance the synthesis of specific cellular structures, thereby facilitating in adaptation to the host microecological environment and expediting infection. Research has demonstrated that QS can both directly or indirectly affect the CCM of numerous pathogenic bacteria, thus altering their virulence and pathogenicity. This article reviews the interplay between QS and CCM in Gram-positive pathogenic bacteria, details the molecular mechanisms by which QS modulates CCM, and lays the groundwork for investigating bacterial pathogenicity and developing innovative infection treatment drugs.

Early brain cognitive development in late preterm infants: an event-related potential and resting EEG study.

BACKGROUND: Late preterm infants (LPIs) are at risk of neurodevelopmental delay. Research on their cognitive development is helpful for early intervention and follow-up. METHODS: Event-related potential (ERP) and resting electroencephalography (RS-EEG) were used to study the brain cognitive function of LPIs in the early stage of life. The Gesell Developmental Scale (GDS) was used to track the neurodevelopmental status at the age of 1 year after correction, and to explore the neurophysiological indicators that could predict the outcome of cognitive development in the early stage. RESULTS: The results showed that mismatch response (MMR) amplitude, RS-EEG power spectrum and functional connectivity all suggested that LPIs were lagging behind. At the age of 1 year after correction, high-risk LPIs showed no significant delay in gross motor function, but lagged behind in fine motor function, language, personal social interaction and adaptability. The ROC curve was used to evaluate the predictive role of MMR amplitude in the brain cognitive development prognosis at 1 year, showing a sensitivity of 80.00% and a specificity of 90.57%. The area under the curve (AUC) was 0.788, with a P-value of 0.007. CONCLUSIONS: Based on our findings we supposed that the cognitive function of LPI lags behind that of full-term infants in early life. Preterm birth and perinatal diseases or high risk factors affected brain cognitive function in LPIs. MMR amplitude can be used as an early predictor of brain cognitive development in LPIs. TRIAL REGISTRATION: This clinical trial is registered with the Chinese Clinical Trial Registry (ChiCTR). TRIAL REGISTRATION NUMBER: ChiCTR2100041929. Date of registration: 2021-01-10. URL of the trial registry record: https://www.chictr.org.cn/ .

Integrated omics analysis reveals the alteration of gut microbiota and fecal metabolites in Cervus elaphus kansuensis.

The gut microbiota is the largest and most complex microecosystem in animals. It is influenced by the host's dietary habits and living environment, and its composition and diversity play irreplaceable roles in animal nutrient metabolism, immunity, and adaptation to the environment. Although the gut microbiota of red deer has been studied, the composition and function of the gut microbiota in Gansu red deer (Cervus elaphus kansuensis), an endemic subspecies of red deer in China, has not been reported. In this study, the composition and diversity of the gut microbiome and fecal metabolomics of C. elaphus kansuensis were identified and compared for the first time by using 16S rDNA sequencing, metagenomic sequencing, and LC-MS/MS. There were significant differences in gut microbiota structure and diversity between wild and farmed C. elaphus kansuensis. The 16S rDNA sequencing results showed that the genus UCRD-005 was dominant in both captive red deer (CRD) and wild red deer (WRD). Metagenomic sequencing showed similar results to those of 16S rDNA sequencing for gut microbiota in CRD and WRD at the phylum and genus levels. 16S rDNA and metagenomics sequencing data suggested that Bacteroides and Bacillus might serve as marker genera for CRD and WRD, respectively. Fecal metabolomics results showed that 520 metabolites with significant differences were detected between CRD and WRD and most differential metabolites were involved in lipid metabolism. The results suggested that large differences in gut microbiota composition and fecal metabolites between CRD and WRD, indicating that different dietary habits and living environments over time have led to the development of stable gut microbiome characteristics for CRD and WRD to meet their respective survival and reproduction needs. KEY POINTS: • Environment and food affected the gut microbiota and fecal metabolites in red deer • Genera Bacteroides and Bacillus may play important roles in CRD and WRD, respectively • Flavonoids and ascorbic acid in fecal metabolites may influence health of red deer.

Efficacy of postoperative analgesia with intravenous paracetamol and mannitol injection, combined with thoracic paravertebral nerve block in post video-assisted thoracoscopic surgery pain: a prospective, randomized, double-blind controlled trial.

BACKGROUND: Although video-assisted thoracoscopic surgery (VATS) has advantages of reduced injury and faster healing, patients still endure moderate and severe postoperative pain. Paracetamol and mannitol injection, the first acetaminophen injection in China, has the advantages of convenient administration, rapid onset of action, and no first-pass effect. This aim of this study was to investigate the efficacy of postoperative analgesia with paracetamol and mannitol injection, combined with thoracic paravertebral nerve block (TPVB) in post VATS pain. METHODS: This study was a single-center, prospective, randomized, double-blind controlled clinical trial. Patients scheduled for VATS were randomly divided into three groups, general anesthesia group (Group C), TPVB group (Group T) and TPVB + paracetamol and mannitol injection group (Group TP). In this study, the primary outcome was determined as visual analog scale (VAS) scores at rest and coughing, the secondary observation outcomes were the first time to use analgesic pump, the total consumption of oxycodone in the analgesic pump, number of effective and total analgesic pump compressions at first 48 h postoperatively, the perioperative consumption of sufentanil, time to extubation, hospital length of stay, urine volume, and the incidence of adverse events. RESULTS: In a state of rest and cough, patients in the Group TP showed significantly lower VAS pain scores at 1, 12, 24, and 48 postoperative-hour compared with Group C and Group T. Intraoperative sufentanil and postoperative oxycodone consumption, the first time to press analgesic pump, the times of effective and total compressions of patient- controlled analgesia (PCA) were lower than those of the Group C and Group T. Interestingly, urine output was higher in Group TP. There were no differences between the three groups in terms of extubation time, length of hospital stay and adverse effects, indicating that intravenous paracetamol and mannitol injection is an effective and safe perioperative analgesia method. CONCLUSIONS: Paracetamol and mannitol injection, combined with TPVB may provide important beneficial effects on acute pain control and reduce the consumption of opioid in patients undergoing VATS. TRIAL REGISTRATION: The trial was registered on Jun 19, 2023 in the Chinese Clinical Trial Registry ( https://www.chictr.org.cn/showproj.html?proj=199315 ), registration number ChiCTR2300072623 (19/06/2023).

Enhanced meningeal lymphatic drainage ameliorates lipopolysaccharide-induced brain injury in aged mice.

BACKGROUND: Sepsis-associated encephalopathy (SAE) is an acute cerebral dysfunction caused by sepsis. Neuroinflammation induced by sepsis is considered a potential mechanism of SAE; however, very little is known about the role of the meningeal lymphatic system in SAE. METHODS: Sepsis was established in male C57BL/6J mice by intraperitoneal injection of 5 mg/kg lipopolysaccharide, and the function of meningeal lymphatic drainage was assessed. Adeno-associated virus 1-vascular endothelial growth factor C (AAV1-VEGF-C) was injected into the cisterna magna to induce meningeal lymphangiogenesis. Ligation of deep cervical lymph nodes (dCLNs) was performed to induce pre-existing meningeal lymphatic dysfunction. Cognitive function was evaluated by a fear conditioning test, and inflammatory factors were detected by enzyme-linked immunosorbent assay. RESULTS: The aged mice with SAE showed a significant decrease in the drainage of OVA-647 into the dCLNs and the coverage of the Lyve-1 in the meningeal lymphatic, indicating that sepsis impaired meningeal lymphatic drainage and morphology. The meningeal lymphatic function of aged mice was more vulnerable to sepsis in comparison to young mice. Sepsis also decreased the protein levels of caspase-3 and PSD95, which was accompanied by reductions in the activity of hippocampal neurons. Microglia were significantly activated in the hippocampus of SAE mice, which was accompanied by an increase in neuroinflammation, as indicated by increases in interleukin-1 beta, interleukin-6 and Iba1 expression. Cognitive function was impaired in aged mice with SAE. However, the injection of AAV1-VEGF-C significantly increased coverage in the lymphatic system and tracer dye uptake in dCLNs, suggesting that AAV1-VEGF-C promotes meningeal lymphangiogenesis and drainage. Furthermore, AAV1-VEGF-C reduced microglial activation and neuroinflammation and improved cognitive dysfunction. Improvement of meningeal lymphatics also reduced sepsis-induced expression of disease-associated genes in aged mice. Pre-existing lymphatic dysfunction by ligating bilateral dCLNs aggravated sepsis-induced neuroinflammation and cognitive impairment. CONCLUSION: The meningeal lymphatic drainage is damaged in sepsis, and pre-existing defects in this drainage system exacerbate SAE-induced neuroinflammation and cognitive dysfunction. Promoting meningeal lymphatic drainage improves SAE. Manipulation of meningeal lymphangiogenesis could be a new strategy for the treatment of SAE.

First description study on molecular characterization of Hemiclepsis khankiana (Hirudinea: Glossiphoniidae) in China.

BACKGROUND: Leeches are an integral component of aquatic biocenosis and can be found in a wide range of ecosystems such as freshwater, saltwater, flowing, and still-water ecosystems. It especially plays an important role in the freshwater benthic community and is an important part of the food web. In this study, a leech species was found in the mantle cavity of wild freshwater mussels in Zigong City, Sichuan Province, China, and its identity was determined through morphological analysis and molecular biological analysis. RESULTS: The leech is Hemiclepsis khankiana, a new species of Hemiclepsis that has been discovered in Russia in recent years. Through morphological analysis, the current survey observed that the morphological characteristics of Hemiclepsis khankiana eyespots were significantly different from the first reported description. The first pair of eyespots on the leech were separated and clear, while it had been reduced to unclear shadows in the previous report. The phylogenetic tree based on the COI gene showed that the COI gene sequence obtained in this study was in the same evolutionary branch as Hemiclepsis khankiana (MN295420, MN295421). Genetically, it was most closely related to Hemiclepsis kasmiana (mean COI p-distance = 3.98%). CONCLUSIONS: The current study reported on the new distribution range of Hemiclepsis khankiana, which was initially discovered in China. This study indicates that the distribution range of the leech species has expanded, laying a foundation for further studies in China.

Fabrication of multifunctional bio-macromolecule organic-inorganic hybrid system for protein silk: Photochromic, UV protection, fire-proof and super durability.

Nowadays, high value-added and multifunctional textiles have attracted widespread attention due to the changing demands of modern life. This study focused on the fabrication of silk with photochromism, flame retardancy, UV resistance and durability using riboflavin sodium phosphate (RSP) and various metal ions (Fe2+, Fe3+, Al3+, and Ti4+). Attractively, the photochromic performance was one of the most distinctive features of the modified silk, and the yellow silk fabric turned into fluorescent green under UV lamp. After a detailed comparison, it was determined that RSP/Fe3+ hybrid system was most effective in improving anti-UV performance of the silk with a high UPF of 25.8, achieving a "Good" level of UV protection. Specifically, it achieved a B1 fire protection with a low damaged-length of 9.4 cm and a high LOI of 28.3 %. Additionally, the modified silk showed the lowest smoke density, reducing by approximately 84.1 % versus that of pristine silk. Moreover, the modified silk was able to meet the B1 classification and the "Good" UV protection requirements even after 75 washing cycles, making it more durable than most functional textiles reported. The further analysis indicated that RSP and metal ions can synergistically enhance the condensed-phase action, thereby improving the fire resistance of silk.

Vector-delivered artificial miRNA effectively inhibits Porcine epidemic diarrhea virus replication.

BACKGROUND: Porcine epidemic diarrhea virus (PEDV) is an α-coronavirus that causes highly contagious intestinal infectious disease, involving clinically characterized by diarrhea, dehydration, vomiting, and high mortality to suckling piglets. As a strategy for antiviral therapy, artificial microRNA (amiRNA) mediated suppression of viral replication has recently become increasingly important. In this study, we evaluated the advantages of using an amiRNA vector against PEDV. METHODS: In this study, we evaluated the advantages of using an amiRNA vector against PEDV. We designed two single amiRNA sequences for different conserved sequences of the PEDV S and N genes, and tested their inhibitory effects on PEDV in Vero cells. RESULTS: It was obvious from the CCK-8 results that the transient transfection of amiRNA was non-toxic to the cells. In addition, our results showed that the transient expression of two amiRNAs (amiRNA-349 and amiRNA-1447) significantly reduced the expression of viral RNA and protein in the cells. The TCID50 results showed that the release of virus particles into the culture supernatant was significantly reduced, with an effect as high as 90%. To avoid virus mutation escape, the above two single amiRNA sequences were tandem in this study (amiRNA-349 + 1447), enabling a single microRNA to be expressed simultaneously. The real-time PCR and Western blot results showed that the inhibitory effect was significantly enhanced in each of the different time periods. The TCID50 results showed that the release of virus particles in the culture supernatant was significantly reduced at the different time periods. CONCLUSIONS: In summary, these results suggest that an RNAi based on amiRNA targeting the conserved region of the virus is an effective method to improve PEDV nucleic acid inhibitors and provide a novel treatment strategy for PEDV infection.

Multi-generation study of heavy ion beam-induced mutations and agronomic trait variations to accelerate rice breeding.

Heavy ion beam (HIB) is an effective physical mutagen that has been widely used in plant mutational breeding. Systemic knowledge of the effects caused by different HIB doses at developmental and genomic levels will facilitate efficient breeding for crops. Here we examined the effects of HIB systematically. Kitaake rice seeds were irradiated by ten doses of carbon ion beams (CIB, 25 - 300 Gy), which is the most widely used HIB. We initially examined the growth, development and photosynthetic parameters of the M1 population and found that doses exceeding 125 Gy caused significant physiological damages to rice. Subsequently, we analyzed the genomic variations in 179 M2 individuals from six treatments (25 - 150 Gy) via whole-genome sequencing (WGS). The mutation rate peaks at 100 Gy (2.66×10-7/bp). Importantly, we found that mutations shared among different panicles of the same M1 individual are at low ratios, validating the hypothesis that different panicles may be derived from different progenitor cells. Furthermore, we isolated 129 mutants with distinct phenotypic variations, including changes in agronomic traits, from 11,720 M2 plants, accounting for a 1.1% mutation rate. Among them, about 50% possess stable inheritance in M3. WGS data of 11 stable M4 mutants, including three lines with higher yields, reveal their genomic mutational profiles and candidate genes. Our results demonstrate that HIB is an effective tool that facilitates breeding, that the optimal dose range for rice is 67 - 90% median lethal dose (LD50), and that the mutants isolated here can be further used for functional genomic research, genetic analysis, and breeding.

Proteomics of immune cells from liver tumors reveals immunotherapy targets.

Elucidating the mechanisms by which immune cells become dysfunctional in tumors is critical to developing next-generation immunotherapies. We profiled proteomes of cancer tissue as well as monocyte/macrophages, CD4+ and CD8+ T cells, and NK cells isolated from tumors, liver, and blood of 48 patients with hepatocellular carcinoma. We found that tumor macrophages induce the sphingosine-1-phospate-degrading enzyme SGPL1, which dampened their inflammatory phenotype and anti-tumor function in vivo. We further discovered that the signaling scaffold protein AFAP1L2, typically only found in activated NK cells, is also upregulated in chronically stimulated CD8+ T cells in tumors. Ablation of AFAP1L2 in CD8+ T cells increased their viability upon repeated stimulation and enhanced their anti-tumor activity synergistically with PD-L1 blockade in mouse models. Our data reveal new targets for immunotherapy and provide a resource on immune cell proteomes in liver cancer.

Physiological and Transcriptomic Analyses Reveal the Effects of Carbon-Ion Beam on Taraxacum kok-saghyz Rodin Adventitious Buds.

Taraxacum kok-saghyz Rodin (TKS) has great potential as an alternative natural-rubber (NR)-producing crop. The germplasm innovation of TKS still faces great challenges due to its self-incompatibility. Carbon-ion beam (CIB) irradiation is a powerful and non-species-specific physical method for mutation creation. Thus far, the CIB has not been utilized in TKS. To better inform future mutation breeding for TKS by the CIB and provide a basis for dose-selection, adventitious buds, which not only can avoid high levels of heterozygosity, but also further improve breeding efficiency, were irradiated here, and the dynamic changes of the growth and physiologic parameters, as well as gene expression pattern were profiled, comprehensively. The results showed that the CIB (5-40 Gy) caused significant biological effects on TKS, exhibiting inhibitory effects on the fresh weight and the number of regenerated buds and roots. Then,15 Gy was chosen for further study after comprehensive consideration. CIB-15 Gy resulted in significant oxidative damages (hydroxyl radical (OH•) generation activity, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity and malondialdehyde (MDA) content) and activated the antioxidant system (superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and ascorbate peroxidase (APX)) of TKS. Based on RNA-seq analysis, the number of differentially expressed genes (DEGs) peaked at 2 h after CIB irradiation. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that DNA-replication-/repair- (mainly up-regulated), cell-death- (mainly up-regulated), plant-hormone- (auxin and cytokinin, which are related to plant morphogenesis, were mainly down-regulated), and photosynthesis- (mainly down-regulated) related pathways were involved in the response to the CIB. Furthermore, CIB irradiation can also up-regulate the genes involved in NR metabolism, which provides an alternative strategy to elevate the NR production in TKS in the future. These findings are helpful to understand the radiation response mechanism and further guide the future mutation breeding for TKS by the CIB.

Comprehensive profiling of serotypes, antimicrobial resistance and virulence of Salmonella isolates from food animals in China, 2015-2021.

Introduction: Salmonella is a ubiquitous foodborne pathogen and mainly transmitted to human farm-to-fork chain through contaminated foods of animal origin. Methods: In this study, we investigated the serotypes, antimicrobial resistance and virulence of Salmonella from China. Results: A total of 617 Salmonella isolates were collected from 4 major food animal species across 23 provi nces in China from 2015-2021. Highest Salmonella prevalence were observed in Guangdong (44.4%) and Sandong (23.7%). Chickens (43.0%) was shown to be the major source of Salmonella contamination, followed by pigs (34.5%) and ducks (18.5%). The number of Salmonella increased significantly from 5.51% to 27.23% during 2015-2020. S. Derby (17.3%), S. Enteritidis (13.1%) and S. Typhimurium (11.4%) were the most common serotypes among 41 serotypes identifiedin this study. Antibiotic susceptibility testing showing that the majority of the Salmonella isolates were resistant to neomycin (99.7%), tetracycline (98.1%), ampicillin (97.4%), sulfadiazine/trimethoprim (97.1%), nalidixic acid (89.1%), doxycycline (83.1%), ceftria xone (70.3%), spectinomycin (67.7%), florfenicol (60.0%), cefotaxime (52.0%) and lomefloxacin (59.8%). The rates of resistance to multiple antibiotics in S. Derby and S.Typhimurium were higher than that in S. Enteritidis. However, the rate of resistance to fosfomycin were observed from higher to lower by S. Derby, S. Enteritidis, and S. Typhimurium. Biofilm formation ability analysis found that 88.49%of the Salmonella were able to produce biofilms, of which 236 Salmonella isolates were strong biofilm producer. Among the 26 types of antibiotics resistance genes (ARGs) were identified in this study, 4 ARGs (tetB,sul2,aadA2, and aph(3')-IIa) were highly prevalent. In addition, 5 ß-lactam resistance genes (bla TEM, bla SHV, bla CMY-2, bla CTX-M, and bla OXA) and 7 quinolone resistance genes (oqxA, oqxB, qnrB, qnrC, qnrD, qnrS, and qeqA) were detected among these isolates. 12 out of 17 virulence genes selected in this study were commonly presented in the chromosomes of tested isolate, with a detection rate of over 80%, including misL, spiA, stn, pagC, iroN, fim, msgA, sopB, prgH, sitC, ttrC, spaN. Discussion: This study provided a systematical updating on surveillance on prevalence of Salmonella from food animals in China, shedding the light on continued vigilance for Salmonella in food animals.

Prevalence and molecular characteristics of mcr-1-positive Escherichia coli isolated from duck farms and the surrounding environments in coastal China.

The emergence of colistin-resistance is considered a threat to public health and colistin-resistant bacteria have recently been reported in animal, environmental and human sources. Whereas, the epidemic and dissemination of colistin-resistant bacteria in duck farms have not been surveyed, especially the surrounding environmental contamination from duck farms. We investigated the prevalence and molecular characteristics of mcr-1-positive E. coli from duck farms in coastal China. 360 mcr-1-positive E. coli isolates were collected from 1112 samples from duck farms and surrounding environments. The prevalence of mcr-1-positive E. coli in Guangdong province was higher than other two provinces we examined. PFGE analysis indicated clonal spread of mcr-1-positive E. coli between duck farms and surrounding environments, including water and soil. MLST analysis demonstrated that ST10 was more common than ST1011, ST117, and ST48. Phylogenomic analysis also suggested mcr-1-positive E. coli collected from distinct cities were assigned to the same lineage and mcr-1 was primarily located on IncI2 and IncHI2 plasmids. Genomic environment analysis showed mobile gene elements ISApl1 most likely plays a key role in the horizontal transmission of mcr-1. WGS further revealed that mcr-1 was found associated with 27 different ARGs. Our findings emphasize the urgent need for effective colistin resistance surveillance in humans, animals and the environment.

Polydopamine-coated 3D-printed ß-tricalcium phosphate scaffolds to promote the adhesion and osteogenesis of BMSCs for bone-defect repair: mRNA transcriptomic sequencing analysis.

Cellular bioactivity and tissue regeneration can be affected by coatings on tissue-engineered scaffolds. Using mussel-inspired polydopamine (PDA) is a convenient and effective approach to surface modification. Therefore, 3D-printed ß-tricalcium phosphate (ß-TCP) scaffolds were coated with PDA in this study. The effects of the scaffolds on the adhesion and osteogenic differentiation of seeded bone marrow mesenchymal stem cells (BMSCs) in vitro and on new-bone formation in vivo were investigated. The potential mechanisms and related differential genes were assessed using mRNA sequencing. It was seen that PDA coating increased the surface roughness of the 3D-printed ß-TCP scaffolds. Furthermore, it prompted the adhesion and osteogenic differentiation of seeded BMSCs. mRNA sequencing analysis revealed that PDA coating might affect the osteogenic differentiation of BMSCs through the calcium signaling pathway, Wnt signaling pathway, TGF-beta signaling pathway, etc. Moreover, the expression of osteogenesis-related genes, such as R-spondin 1 and chemokine c-c-motif ligand 2, was increased. Finally, both the 3D-printed ß-TCP scaffolds and PDA-coated scaffolds could significantly accelerate the formation of new bone in critical-size calvarial defects in rats compared with the control group; and the new bone formation was obviously higher in the PDA-coated scaffolds than in ß-TCP scaffolds. In summary, 3D-printed ß-TCP scaffolds with a PDA coating can improve the physicochemical characteristics and cellular bioactivity of the scaffold surface for bone regeneration. Potential differential genes were identified, which can be used as a foundation for further research.

MiRNA Profiling and Its Potential Roles in Rapid Growth of Velvet Antler in Gansu Red Deer (Cervus elaphus kansuensis).

A significant variety of cell growth factors are involved in the regulation of antler growth, and the fast proliferation and differentiation of various tissue cells occur during the yearly regeneration of deer antlers. The unique development process of velvet antlers has potential application value in many fields of biomedical research. Among them, the nature of cartilage tissue and the rapid growth and development process make deer antler a model for studying cartilage tissue development or rapid repair of damage. However, the molecular mechanisms underlying the rapid growth of antlers are still not well studied. MicroRNAs are ubiquitous in animals and have a wide range of biological functions. In this study, we used high-throughput sequencing technology to analyze the miRNA expression patterns of antler growth centers at three distinct growth phases, 30, 60, and 90 days following the abscission of the antler base, in order to determine the regulatory function of miRNA on the rapid growth of antlers. Then, we identified the miRNAs that were differentially expressed at various growth stages and annotated the functions of their target genes. The results showed that 4319, 4640, and 4520 miRNAs were found in antler growth centers during the three growth periods. To further identify the essential miRNAs that could regulate fast antler development, five differentially expressed miRNAs (DEMs) were screened, and the functions of their target genes were annotated. The results of KEGG pathway annotation revealed that the target genes of the five DEMs were significantly annotated to the "Wnt signaling pathway", "PI3K-Akt signaling pathway", "MAPK signaling pathway", and "TGF-ß signaling pathway", which were associated with the rapid growth of velvet antlers. Therefore, the five chosen miRNAs, particularly ppy-miR-1, mmu-miR-200b-3p, and novel miR-94, may play crucial roles in rapid antler growth in summer.

Three-dimensional bioprinted BMSCs-laden highly adhesive artificial periosteum containing gelatin-dopamine and graphene oxide nanosheets promoting bone defect repair.

The periosteum is a connective tissue membrane adhering to the surface of bone tissue that primarily provides nutrients and regulates osteogenesis during bone development and injury healing. However, building an artificial periosteum with good adhesion properties and satisfactory osteogenesis for bone defect repair remains a challenge, especially using three-dimensional (3D) bioprinting. In this study, dopamine was first grafted onto the molecular chain of gelatin usingN-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride andN-hydroxysuccinimide (NHS) to activate the carboxyl group and produce modified gelatin-dopamine (GelDA). Next, a methacrylated gelatin, methacrylated silk fibroin, GelDA, and graphene oxide nanosheet composite bioink loaded with bone marrow mesenchymal stem cells was prepared and used for bioprinting. The physicochemical properties, biocompatibility, and osteogenic roles of the bioink and 3D bioprinted artificial periosteum were then systematically evaluated. The results showed that the developed bioink showed good thermosensitivity and printability and could be used to build 3D bioprinted artificial periosteum with satisfactory cell viability and high adhesion. Finally, the 3D bioprinted artificial periosteum could effectively enhance osteogenesis bothin vitroandin vivo. Thus, the developed 3D bioprinted artificial periosteum can prompt new bone formation and provides a promising strategy for bone defect repair.

Development of a quantitative structure-activity relationship model for predicting quantum yield of hydroxyl radical generation from organic compounds.

Organic compounds are capable of generating hydroxyl radicals (˙OH) through their excited triplet states in natural water. It is of significance to reveal the underlying mechanism of the generation and obtain the generation quantum yield of ˙OH from organic compounds for better understanding of its involvement in indirect photochemical processes in the environment. In this study, the ˙OH quantum yields (Φ˙OH) of 20 organic compounds were determined by photochemical experiments. The calculated Φ˙OH values for the selected organic compounds vary from (1.2 ± 0.39) × 10-5 to (7.2 ± 0.16) × 10-4. A quantitative structure-activity relationship (QSAR) model for log Φ˙OH was developed and the established model was proven to have a proper goodness of fit, robustness, and predictive ability. The QSAR model was successfully used to predict the Φ˙OH value of organic pollutants. Mechanistic interpretation showed that the electron distribution and the electronegativity of organic compounds are the most important factors that determine the generation of ˙OH. The results are helpful for understanding the generation mechanism of ˙OH from organic compounds and also provide insights into the generation of ˙OH from dissolved organic matter in natural water.

RNA-Seq Reveals Protective Mechanisms of Mongolian Medicine Molor-Dabos-4 on Acute Indomethacin-Induced Gastric Ulcers in Rats.

This study aimed to apply transcriptomics to determine how Molor-Dabos-4 (MD-4) protects healthy rats against indomethacin (IND)-induced gastric ulcers and to identify the mechanism behind this protective effect. Rats were pretreated with MD-4 (0.3, 1.5, or 3 g/kg per day) for 21 days before inducing gastric ulcers by oral administration with indomethacin (30 mg/kg). Unulcerated and untreated healthy rats were used as controls. Effects of the treatment were assessed based on the ulcer index, histological and pathological examinations, and indicators of inflammation, which were determined by enzyme-linked immunosorbent assay. Transcriptomic analysis was performed for identifying potential pharmacological mechanisms. Eventually, after identifying potential target genes, the latter were validated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). After pretreatment with MD-4, gastric ulcers, along with other histopathological features, were reduced. MD-4 significantly (p < 0.05) increased the superoxide dismutase (SOD) levels in ulcers and reduced pepsin, TNF-α, and IL-6 levels. RNA-seq analysis identified a number of target genes on which MD-4 could potentially act. Many of these genes were involved in pathways that were linked to anti-inflammatory and antioxidant responses, and other protective mechanisms for the gastric mucosa. qRT-PCR showed that altered expression of the selected genes, such as Srm, Ryr-1, Eno3, Prkag3, and Eef1a2, was consistent with the transcriptome results. MD-4 exerts protective effects against IND-induced gastric ulcers by reducing inflammatory cytokines and pepsin and increasing the expression of SOD levels. Downregulation of Srm, Ryr-1, Eno3, Prkag3, and Eef1a2 genes involved in regulating arginine and proline metabolism, calcium signaling pathway, HIF-1 signaling pathway, oxytocin signaling pathway, and legionellosis are possibly involved in MD-4-mediated protection against gastric ulcers.

Lateral-Opening Injection Tool Used in Percutaneous Vertebroplasty to Treat Asymptomatic Osteoporotic Vertebral Burst Fractures: A Retrospective Study.

OBJECTIVE: The adequate management of asymptomatic osteoporotic vertebral burst fractures (OVBFs) was still controversial. Percutaneous vertebroplasty (PVP) could achieve quick recovery with minor trauma, but there were certain safety problems by traditional bone cement injection method. Thus, the aim of this study was to assess the efficacy of lateral-opening injection tool used in PVP treating patients with asymptomatic OVBFs. METHODS: This was a retrospective study of OVBFs treated in our institute from March 2016 to March 2020. A total of 66 patients (mean age 72.10 ± 7.98 years, with 21 men and 45 women) who were diagnosed with acute asymptomatic OVBFs with mild spinal canal compromise were treated with PVP by using a lateral-opening injection tool. Two puncture needles were simultaneously placed transpedicularly in the fractured vertebra, and the inner core was removed, and the lateral-opening injection tool was inserted. The adjustment of lateral hole was to improve the distribution height of bone cement and avoid the entry of bone cement into the posterior wall of vertebral body. Related clinical outcomes and images were assessed, including back pain (visual analog scale [VAS]), vertebral height ratio (fractured vertebral height/average adjacent nonfractured vertebral height), kyphosis Cobb angle, union of the fractured vertebral posterior wall, distribution of bone cement, surgical data, and complications. RESULTS: The average follow-up time of all cases was 21.23 ± 9.35 months. The mean amount of bone cement was 3.28 ± 0.35 ml in the vertebrae and the mean operative time was 34.02 ± 5.23 min. There were 60 cases of bone cement that contacted the upper and lower endplates on at least one side. There was no cement leakage into the spinal canal or fracture displacement of the posterior wall of the vertebral body in all cases. The VAS scores were 3.78 ± 0.42 at 1 day postoperatively and 0.53 ± 0.40 at the last follow-up, significantly lower than 8.40 ± 0.48 preoperatively (p < 0.05). The average height ratio of anterior, middle, and posterior vertebral body after operation increased compared with that pre-operation (p < 0.05), and the postoperative kyphosis angle decreased (p < 0.05). At 6 months follow-up, there was no significant height loss of the vertebral body. Computed tomography examination 3 months postoperatively showed that the fracture of posterior vertebral wall healed well in all cases. There were seven cases of bone cement leakage without clinical symptoms and two adjacent vertebral fractures caused by falling. There were no cases of deep vein embolism, lower limb muscle atrophy, pneumonia, decubitus. CONCLUSION: The lateral opening tool can be safely and effectively used in the PVP treatment on asymptomatic OVBFs with mild spinal canal compromise.