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The response to ischemia in peripheral artery disease (PAD) depends on compensatory neovascularization and coordination of tissue regeneration. Identifying novel mechanisms regulating these processes is critical to the development of nonsurgical treatments for PAD. E-selectin is an adhesion molecule that mediates cell recruitment during neovascularization. Therapeutic priming of ischemic limb tissues with intramuscular E-selectin gene therapy promotes angiogenesis and reduces tissue loss in a murine hindlimb gangrene model. In this study, we evaluated the effects of E-selectin gene therapy on skeletal muscle recovery, specifically focusing on exercise performance and myofiber regeneration. C57BL/6J mice were treated with intramuscular E-selectin/adeno-associated virus serotype 2/2 gene therapy (E-sel/AAV) or LacZ/AAV2/2 (LacZ/AAV) as control and then subjected to femoral artery coagulation. Recovery of hindlimb perfusion was assessed by laser Doppler perfusion imaging and muscle function by treadmill exhaustion and grip strength testing. After three postoperative weeks, hindlimb muscle was harvested for immunofluorescence analysis. At all postoperative time points, mice treated with E-sel/AAV had improved hindlimb perfusion and exercise capacity. E-sel/AAV gene therapy also increased the coexpression of MyoD and Ki-67 in skeletal muscle progenitors and the proportion of Myh7+ myofibers. Altogether, our findings demonstrate that in addition to improving reperfusion, intramuscular E-sel/AAV gene therapy enhances the regeneration of ischemic skeletal muscle with a corresponding benefit on exercise performance. These results suggest a potential role for E-sel/AAV gene therapy as a nonsurgical adjunct in patients with life-limiting PAD.

Cyclopentanol (CPL) was an eco-friendly solvent as well as important platform chemical which could be generated from biomass-derived furfural (FFA). In this paper, a series of Ni, Cu, Mo, Co bimetallic catalysts with different metals loadings supported on carbon nanotubes (CNT) were synthesized by an impregnation method for aqueous-phase hydrogenation of FFA to obtain CPL. Various effects of reaction parameters such as reaction solvent, reaction temperature, reaction time and different loading amounts of Ni over bimetallic Ni-based CNT catalysts were fully investigated. Among the catalysts studied, (15 + 5) wt% NiCu/CNT catalysts showed a high conversion of FFA and 88% selectivity towards CPL in water and 96% selectivity towards acetal in methanol at the mild condition of 160℃, 2 MPa hydrogen and 4 h reaction time. NiCu bimetallic synergistic effect was interpreted through H2-TPR and NH3-TPD measurement and a possible pathway was proposed. The features of the CNT-supported catalysts were investigated via XRD, XPS, TEM, H2-TPR and NH3-TPD. The Ni and bimetallic NiCu catalysts synthesized in this work were inexpensive and simple, which made them a promising candidate for the conversion of biomass-derived FFA to CPL.

Efficient and nondestructive technology for identifying wood species facilitates the transition from digital forestry to smart forestry. While near-infrared spectroscopy applied to wood identification is well documented, the detailed mechanisms for chemometrics remain unclear. In this study, twelve wood species were identified by using near-infrared spectroscopy combined with six machine learning algorithms (support vector machine, logistic regression, naïve Bayes, k-nearest neighbors, random forest, and artificial neural network). Above all, isolated forest and local outlier factor were used to detect and exclude outliers. Then feature engineering strategies were developed from three perspectives to process feature matrices: feature selection, feature extraction, and feature selection combined with feature extraction. Next, the learning curve, grid search method, and K-fold cross-validation were used to optimize the model parameters. Finally, the accuracy, operation time, and confusion matrix were used to evaluate the model performance. When the local outlier factor was used to remove outliers and principal component analysis was used to extract features, the support-vector-machine-based wood-species identification model produced the most accurate results, with 98.24% accuracy. These results offer new avenues for constructing automatic wood-identification systems.

Noroviruses (NoVs) are the primary cause of acute gastroenteritis worldwide. Histo-blood group antigens (HBGAs) are receptors or attachment factors that affect the prevalence and host susceptibility of NoVs. GII.6 NoV is one of the predominant genotypes in humans, which recognizes the type ABO secretor of HBGAs. However, the structural basis of GII.6 NoV's interaction with HBGAs receptors remains elusive. In this study, we investigated the binding features of the GII.6 strain to HBGAs using saliva- and glycan-ELISA assays and characterized the molecular basis of the GII.6 virus that recognizes H disaccharide. We showed that the GII.6 ​P domain recognized some A and O secretor's saliva samples, most B secretor's saliva samples, and H disaccharide antigen, but did not bind non-secretors' saliva. Further, we determined the crystal structures of GII.6 and its complex with H disaccharides at 1.7 ​Å, revealing that the P domain of GII.6 shares the conventional binding interface and mode of GII HBGAs. Single residue mutations at the GII.6-H binding sites could inhibit the binding of GII.6 to HBGAs, demonstrating that the interaction residues were crucial in maintaining NoV-glycan integrity. Finally, structural and sequence analyses showed that the major residues of the GII.6-H interaction were conserved among NoVs in the GII genogroup. Taken together, our study characterized the functional and structural features of GII.6 that allow it to interact with HBGAs, and shed light on NoV evolution, epidemiology, and anti-viral drug development.

Northern peatlands are globally important carbon stores. With increasing fire frequency, the re-establishment of bryophytes becomes crucial for their carbon sequestration. Smoke-responsive germination is a common trait of seeds in fire-prone ecosystems but has not been demonstrated in bryophytes. To investigate the potential role of smoke in post-fire peatland recovery, we tested the germination of spores of 15 bryophyte species after treatment with smoke-water. The smoke responsiveness of spores with different laboratory storage times and burial depths/age (3–200 years) was subsequently tested. Smoke increased the germination percentage for 10 of the species and the germination speed for four of these. Smoke responsiveness increased along the fire frequency gradient from open expanse to forest margin, consistent with the theory that this selects for the maintenance of fire-adapted traits. Smoke enhanced the germinability of 1-year but not 4-year laboratory-stored spores, and considerably increased the germinability of spores naturally buried in peat for up to ~200 years. The effect of fire may be overlooked in non-fire-prone ecosystems, such as those in which wetland bryophytes dominate. Our study reveals a mechanism by which an increase in fire frequency may lead to shifts in species dominance, which may affect long-term carbon sequestration in peatlands.

Natural products (NPs) and their structural analogs represent a major source of novel drug development for disease prevention and treatment. The development of new drugs from NPs includes two crucial aspects. One is the discovery of NPs from medicinal plants/microorganisms, and the other is the evaluation of the NPs in vivo at various physiological and pathological states. The heterogeneous spatial distribution of NPs in medicinal plants/microorganisms or in vivo can provide valuable information for drug development. However, few molecular imaging technologies can detect thousands of compounds simultaneously on a label-free basis. Over the last two decades, mass spectrometry imaging (MSI) methods have progressively improved and diversified, thereby allowing for the development of various applications of NPs in plants/microorganisms and in vivo NP research. Because MSI allows for the spatial mapping of the production and distribution of numerous molecules in situ without labeling, it provides a visualization tool for NP research. Therefore, we have focused this mini-review on summarizing the applications of MSI technology in discovering NPs from medicinal plants and evaluating NPs in preclinical studies from the perspective of new drug research and development (RD). Additionally, we briefly reviewed the factors that should be carefully considered to obtain the desired MSI results. Finally, the future development of MSI in new drug RD is proposed.

Isopsoralen, one of the main active and quality-control compounds inThis study investigates the effect of three- or seven-day exposure of low dose isopsoralen (80 mg/kg) on bile acid homeostasis in C57BL/6J mice.Forty-two C57BL/6J mice were randomly divided into control, three- and seven-day groups (In the study, isopsoralen increased the levels of serum AST, ALT in three- and seven-day groups, and caused vacuolar degeneration and swelling in the liver. Canalicular efflux transporters BSEP, OSTα, MRP2, MRP3, and basolateral uptake transporters NTCP, OATP4 were inhibited after seven-day-administration. Moreover, amino acid binding enzymes (BAAT and BACS) were also inhibited after seven-day-administration. The composition of BAs changed greatly and the concentration of some unconjugated-BAs which have stronger hydrophobicity, such as CA, CDCA, was significantly increased.Isopsoralen (80 mg/kg) caused hepatotoxicity after short-term exposure by inhibiting the expression of efflux transporters, amino acid binding enzymes, and disrupting BAs spectrum.

Based on sedimentary theory and high-resolution sequence stratigraphic theory, Denglouku third member in the south of Shuangcheng area is finely divided into a long-term reference surface cycle, 3 medium-term reference surface cycles and 20 short-term reference surface cycles. Denglouku third member is divided into three sand groups from top to bottom according to the medium-term reference surface cycles, and 6 layers, 6 layers, 8 layers in the groups respectively. Through fine observation of rock cores and data analysis of nearly one hundred wells, it is believed that alluvial fan facies, fluvial facies and delta facies are developed in the study area, which can be further divided into 6 subfacies and 12 microfacies. After the analysis to the plane distribution and vertical evolution characteristics of sedimentary facies, it is found that Denglouku third member in the south of Shuangcheng area shows a water-transgression sedimentary cycle from bottom to top which reflects the sedimentary process of water body gradually deepening.

Lei Zhang, Jun Zhao, Yun Bai, Xiuping Liu Department of Obstetrics and Gynecology, the Third Hospital of Hebei Medical University, Shijiazhuang City, 050051, People’s Republic of ChinaCorrespondence: Lei Zhang, Department of Obstetrics and Gynecology, the third hospital of Hebei Medical University, No. 139 of Ziqiang Road, Qiaoxi District, Shijiazhuang City, Hebei Province, 050051, People’s Republic of China, Tel +86-0311-88602058, Email leizhang1442@163.comObjective: This study aimed to compare fertility outcomes in patients who underwent different laparoscopic surgeries and to determine the most beneficial surgical treatment for tubal ectopic pregnancy (EP) patients who wished to become pregnant in the future.Methods: In this retrospective study, patients aged 18– 36 years, who had been diagnosed with a tubal EP in our hospital, were enrolled. Based on the treatment methods, the patients were divided into three groups, ie a salpingectomy group, a salpingotomy with suturing group and a salpingotomy without suturing group. The follow-up time for the enrolled patients was more than three years. Serum beta (β)-human chorionic gonadotropin (β-HCG) levels were monitored after surgery. The intrauterine pregnancy (IUP) rate at 12, 24 and 36 months postoperatively, and recurrent EP rate were compared.Results: The median time for β-HCG level returning to normal in the salpingectomy group was much shorter than in the salpingotomy with suturing or salpingotomy without suturing groups (P < 0.001). The 12, 24 and 36-month IUP rates among the three groups were not significantly different. A recurrent EP was found in only one patient in the salpingotomy with suturing group and two patients in the salpingotomy without suturing group.Conclusion: In this study, we found that salpingectomy and salpingotomy with or without suturing methods reflected no significant differences in fertility outcomes for tubal EP patients.Keywords: ectopic pregnancy, salpingectomy, salpingotomy, intrauterine pregnancy, fertility

Co-doped LaFe1−xCoxO3 (x = 0, 0.1, 0.2, 0.4, 0.6, 0.9) nanomaterial films were prepared via a citric acidassisted sol–gel method and characterized by various techniques. Compared with pure LaFeO3, the optimum operating temperature of the LaFe0.9Co0.1O3 gas sensor dropped to 110 °C from 140 °C. The response value to 100 ppm acetone was 35.89, with a fast response–recovery time of 14/9 s. The enhanced gas sensitivity may be attributed to the higher number of surface oxygen vacancies and larger specific surface area of LaFe0.9Co0.1O3. Doping with Co ions improved the moisture resistance of the LaFeO3 sensor at 18%–54% relative humidity. Appropriate doping of Co3+ into LaFeO3 nanofibers is a promising method for designing and fabricating an acetone sensor with high gas-sensing performance.

Leaf senescence is the final stage of leaf development which is induced by many genetic and environmental factors. To reveal the role of transcription factors in leaf senescence, we studied the function of a bHLH transcription factor ZmbHLH121 in maize. The overexpression of ZmbHLH121 exhibited phenotypes with leaf senescence. Higher expression pattern of ZmbHLH121 was observed in the immature leaves through expression analysis at early vegetative developmental stages. Results of 3,3-diaminobenzidine (DAB), nitroblue tetrazolium chloride (NBT) histochemical analysis, quantitative measurement of reactive oxygen species (ROS), chlorophyll quantification and transcriptome analysis revealed that, ZmbHLH121 positively regulated leaf senescence by accelerating ROS production and chlorophyll breakdown in maize leaves. It is suggested that, ZmbHLH121 regulated leaf senescence might be due to the excess amount of ROS production and chlorophyll loss in leaves. This study provided useful clue about the mechanism of ZmbHLH121 mediated leaf senescence.

Our country’s international status as a cultural power has been further enhanced, and the protection of intangible cultural heritage containing the essence of traditional culture is also gradually being carried out. In addition, with the rapid development of the digital environment, the public’s cultural needs continue to grow, and the contradiction between the supply and demand of public digital cultural services continues to intensify. Converting intangible cultural heritage into digital form for protection and providing resource services for the public has become an important trend in the protection and inheritance of intangible cultural heritage at home and abroad, and it is also an inevitable requirement to solve the contradiction between supply and demand. Improving public cultural services is one of the key projects. At present, our country’s research and practice of intangible cultural heritage digitization and services are also in progress, but there is no research on intangible cultural heritage digital resource services and system construction from the perspective of information service elements. Based on the digital resource service of intangible cultural heritage, the manual course is one of the main skill courses for preschool education majors. At this stage, the short class hours of manual courses, the lack of class hours, the low utilization rate of teaching materials, and the disconnection between the content and the needs of the kindergarten are all problems that need to be solved at present. Just relying on cross-references between schools, the manual knowledge and skills mastered by graduates are not comprehensive enough to complete the manual tasks assigned by the kindergarten. This paper implements the concept of intangible cultural heritage and hopes that by studying the manual knowledge and skills that today’s kindergarten teachers need to possess, the content of existing manual courses can be adjusted in a targeted manner, so that the electronic culture dissemination of manual curriculum resources for preschool education is more reasonable, meeting the requirements of kindergarten teachers in terms of manual knowledge and skills.

Background Cattle (Bos taurus) are a major large livestock, however, compared with other species, the transcriptional specificity of bovine oocyte development has not been emphasised. Results To reveal the unique transcriptional signatures of bovine oocyte development, we used integrated multispecies comparative analysis and weighted gene co-expression network analysis (WGCNA) to perform bioinformatic analysis of the germinal follicle (GV) and second meiosis (MII) gene expression profile from cattle, sheep, pigs and mice. We found that the expression levels of most genes were down-regulated from GV to MII in all species. Next, the multispecies comparative analysis showed more genes involved in the regulation of cAMP signalling during bovine oocyte development. Moreover, the green module identified by WGCNA was closely related to bovine oocyte development. Finally, integrated multispecies comparative analysis and WGCNA picked up 61 bovine-specific signature genes that participate in metabolic regulation and steroid hormone biosynthesis. Conclusion In a short, this study provides new insights into the regulation of cattle oocyte development from a cross-species comparison.

Bromodomain and extraterminal inhibitors (BETi) are promising cancer therapies, yet prominent side effects of BETi at effective doses have been reported in phase I clinical trials. Here, we screened a panel of small molecules targeting epigenetic modulators against human metastatic melanoma cells. Cells were pretreated with or without ascorbate (vitamin C), which promotes DNA demethylation and subsequently changes the sensitivity to drugs. Top hits were structurally unrelated BETi, including JQ1, I-BET151, CPI-203, and BI-2536. Ascorbate enhanced the efficacy of BETi by decreasing acetylation of histone H4, but not H3, while exerting no effect on the expression of BRD proteins. Histone acetyltransferase 1 (HAT1), which catalyzes H4K5ac and H4K12ac, was downregulated by ascorbate mainly via the TET-mediated DNA hydroxymethylation pathway. Loss of H4ac, especially H4K5ac and H4K12ac, disrupted the interaction between BRD4 and H4 by which ascorbate and BETi blocked the binding of BRD4 to acetylated histones. Cotreatment with ascorbate and JQ1 induced apoptosis and inhibited proliferation of cultured melanoma cells. Ascorbate deficiency as modeled in Gulo−/− mice diminished the treatment outcome of JQ1 for melanoma tumorgraft. In contrast, ascorbate supplementation lowered the effective dose of JQ1 needed to successfully inhibit melanoma tumors in mice. On the basis of our findings, future clinical trials with BETi should consider ascorbate levels in patients. Furthermore, ascorbate supplementation might help reduce the severe side effects that arise from BETi therapy by reducing the dosage necessary for treatment.Significance: This study shows that ascorbate can enhance the efficacy of BET inhibitors, providing a possible clinical solution to challenges arising in phase I trials from the dose-dependent side effects of this class of epigenetic therapy. Cancer Res; 78(2); 572–83. ©2017 AACR.

This file contains the following supplementary figures, tables and other materials. Figure S1: The expression of BRD2, BRD3 and BRD4 in melanocytes and melanoma cells. Figure S2: Knocking down the expression of BRD4 by siRNA. Figure S3: The effect of ascorbate on the expression of BRDs. Figure S4: hMeDIP-qPCR of HAT1 in its promoter and gene body. Figure S5: Decreased acetylation of soluble H4 by ascorbate treatment. Figure S6: The effect of ascorbate on H4K8ac and H4K16ac. Figure S7: Isobologram analysis of JQ1 and ascorbate interaction in A2058 cells. Figure S8: Ascorbate sensitizes murine melanoma cell B16-F10 to BETi. Table S1. Primers for hMeDIP-qPCR of HAT1. Table S2: Epigenetic drug screening panel. Table S3: Ascorbate decreases the EC50 of BET inhibitors in melanoma cell lines. Supplementary Material and Methods Supplementary reference

Supplementary Table 1 from Active Notch1 Confers a Transformed Phenotype to Primary Human Melanocytes

Supplementary Methods and Materials from Active Notch1 Confers a Transformed Phenotype to Primary Human Melanocytes

Supplementary Figure 1 from Active Notch1 Confers a Transformed Phenotype to Primary Human Melanocytes

Supplementary Figure Legends 1-2 from Active Notch1 Confers a Transformed Phenotype to Primary Human Melanocytes

Supplementary Figure 2 from Active Notch1 Confers a Transformed Phenotype to Primary Human Melanocytes

The Wnt/β-catenin signaling pathway is a classical Wnt pathway that regulates the stability and nuclear localization of β-catenin and plays an important role in adult heart development and cardiac tissue homeostasis. In recent years, an increasing number of researchers have implicated the dysregulation of this signaling pathway in a variety of cardiac diseases, such as myocardial infarction, arrhythmias, arrhythmogenic cardiomyopathy, diabetic cardiomyopathies, and myocardial hypertrophy. The morbidity and mortality of cardiac diseases are increasing, which brings great challenges to clinical treatment and seriously affects patient health. Thus, understanding the biological roles of the Wnt/β-catenin pathway in these diseases may be essential for cardiac disease treatment and diagnosis to improve patient quality of life. In this review, we summarize current research on the roles of β-catenin in human cardiac diseases and potential inhibitors of Wnt/β-catenin, which may provide new strategies for cardiac disease therapies.

To provide a basis for further optimization of the polio sequential immunization schedule, this study evaluated the effectiveness of booster immunization with one dose of bivalent oral poliovirus vaccine (bOPV) at 48 months of age after different primary polio immunization schedules. At 48 months of age, one dose of bOPV was administered, and their poliovirus types 1–3 (PV1, PV2, and PV3, respectively)-specific neutralizing antibody levels were determined. Participants found to be negative for any type of PV-specific neutralizing antibody at 24, 36, or 48 months of age were re-vaccinated with inactivated polio vaccine (IPV). The 439 subjects who received a bOPV booster immunization at the age of 48 months had lower PV2-specific antibody levels compared with those who received IPV. One dose of IPV during basic polio immunization induced the lowest PV2-specific antibody levels. On the basis of our findings, to ensure that no less than 70% of the vaccinated have protection efficiency, we recommend the following: if basic immunization was conducted with 1IPV + 2bOPV (especially Sabin strain-based IPV), a booster immunization with IPV is recommended at 36 months of age, whereas if basic immunization was conducted with 2IPV + 1bOPV, a booster immunization with IPV is recommended at 48 months of age. A sequential immunization schedule of 2IPV + 1bOPV + 1IPV can not only maintain high levels of antibody against PV1 and PV3 but also increases immunity to PV2 and induces early intestinal mucosal immunity, with relatively good safety. Thus, this may be the best sequential immunization schedule for polio in countries or regions at high risk for polio.

Anti-Aβ therapy has dominated clinical trials for the prevention and treatment of Alzheimer's disease (AD). However, suppressing Aβ aggregation and disintegrating mature fibrils simultaneously remains a great challenge. In this work, we developed a new strategy using a charged tubular supramolecule (CTS) with pillar[5]arene as the backbone and modifying amino and carboxyl groups at the tubular terminals (noted as CTS-A, CTS-A/C, and CTS-C, respectively) to suppress Aβ fibrillation for the first time. According to the spectroscopic and microscopic characterizations, Aβ40 fibrillation can be efficiently suppressed by CTS-A in a very low inhibitor:peptide (I:P) molar ratio (1:10). A greatly alleviated cytotoxic effect of Aβ peptides after the inhibition or disaggregation process is further disclosed. The well-organized supramolecular structure drives multivalent interaction and gains enhanced efficiency on amyloid fibrillar modulation. These results open a new path for the design of supramolecules in the application of AD treatment.

Background: Drug-induced liver injury (DILI) is a potentially serious adverse drug reaction. Due to the lack of definite etiology, specific clinical manifestations, and diagnostic methods, its prediction and diagnosis are challenging. Elderly individuals are deemed to be at high risk for DILI due to abnormal pharmacokinetics, aging tissue repair function, comorbidities, and taking multiple drugs. This study aimed to identify the clinical characteristics and explore the risk factors associated with the severity of illness in elderly patients with DILI.Methods: In the present study, the clinical characteristics at the time of liver biopsy of consecutive patients with biopsy-proven DILI who presented at our hospital from June 2005 to September 2022 were evaluated. Hepatic inflammation and fibrosis were assessed according to the Scheuer scoring system. The presence of autoimmunity was considered if IgG level >1.1 × ULN (1826 mg/dL), or high titer (>1:80) of ANA, or SMA.Results: In total, 441 patients were enrolled, and the median age was 63.3 years (IQR, 61.0–66.0); 122 (27.7%), 195 (44.2%), or 124 (28.1%) were classified as having minor, moderate, or severe hepatic inflammation, respectively; and 188 (42.6%), 210 (47.6%) or 43 (9.8%) patients presented minor, significant fibrosis or cirrhosis, respectively. Female sex (73.5%) and the cholestatic pattern (47.6%) were dominant in elderly DILI patients. Autoimmunity existed in 201 patients (45.6%). Comorbidities were not directly associated with the severity of DILI. PLT (OR: 0.994, 95% CI: 0.991–0.997; p < 0.001), AST (OR: 1.001, 95% CI: 1.000–1.003, p = 0.012), TBIL (OR: 1.006, 95% CI: 1.003–1.010, p < 0.001), and autoimmunity (OR: 1.831, 95% CI: 1.258–2.672, p = 0.002) were associated with the degree of hepatic inflammation. Meanwhile, PLT (OR: 0.990, 95% CI: 0.986–0.993, p < 0.001), TBIL (OR: 1.004, 95% CI: 1.000–1.007, p = 0.028), age (OR: 1.123, 95% CI: 1.067–1.183, p < 0.001), and autoimmunity (OR: 1.760, 95% CI: 1.191–2.608, p = 0.005) were associated with the stage of hepatic fibrosis.Conclusion: This study revealed that the presence of autoimmunity represents a more serious illness state of DILI, deserving more intensive monitoring and progressive treatment.

Objective: To isolate a prevalent G9P[8] group A rotavirus (RVA) strain (N4006) in China and investigate its genomic and evolutionary characteristics, with the goal of facilitating the development of a new rotavirus vaccine. Methods: An RVA strain of the G9P[8] genotype from a diarrhea sample was passaged in MA104 cells. The strain was evaluated by SEM, polyacrylamide gel electrophoresis, and indirect immunofluorescence assay. The complete genome of the strain was obtained by RT-PCR and sequencing. The genomic and evolutionary characteristics of the strain were evaluated by nucleic acid sequence analysis with MEGA ver. 5.0.5 and DNASTAR software. The neutralizing epitopes of VP7 and VP4 (VP5* and VP8*) were analyzed using BioEdit ver. 7.0.9.0 and PyMOL ver. 2.5.2. Results: The N4006 strain (G9P[8] genotype) was adapted in MA104 cells with a high titer (105.5 PFU/mL). Whole-genome sequence analysis showed N4006 to be a reassortant rotavirus of Wa-like G9P[8] RVA and the NSP4 gene of DS-1-like G2P[4] RVA, with the genotype constellation G9-P[8]-I1-R1-C1-M1-A1-N1-T1-E2-H1 (G9P[8]-E2). Phylogenetic analysis indicated that N4006 had a common ancestor with Japanese G9P[8]-E2 rotavirus strains. Neutralizing epitope analysis showed that VP7, VP5*, and VP8* of N4006 had low homology with vaccine strains of the same genotype and marked differences with vaccine strains of other genotypes. Conclusion: The G9P[8] genotype rotavirus with the G9-P[8]-I1-R1-C1-M1-A1-N1-T1-E2-H1 (G9P[8]-E2) constellation predominates in China and may originate from reassortment between Japanese G9P[8] with Japanese DS-1-like G2P[4] rotaviruses. The antigenic variation of N4006 with the vaccine strain necessitates evaluation of the effect of the rotavirus vaccine on G9P[8]-E2 genotype rotavirus.

Progressive peripheral arterial disease (PAD) can result in chronic limb-threatening ischemia (CLTI) characterized by clinical complications including rest pain, gangrene and tissue loss. These complications can propagate even more precipitously in the setting of common concomitant diseases in patients with CLTI such as diabetes mellitus (DM). CLTI ulcers are cutaneous, non-healing wounds that persist due to the reduced perfusion and dysfunctional neovascularization associated with severe PAD. Existing therapies for CLTI are primarily limited to anatomic revascularization and medical management of contributing factors such as atherosclerosis and glycemic control. However, many patients fail these treatment strategies and are considered “no-option,” thereby requiring extremity amputation, particularly if non-healing wounds become infected or fulminant gangrene develops. Given the high economic burden imposed on patients, decreased quality of life, and poor survival of no-option CLTI patients, regenerative therapies aimed at neovascularization to improve wound healing and limb salvage hold significant promise. Cell-based therapy, specifically utilizing mesenchymal stem/stromal cells (MSCs), is one such regenerative strategy to stimulate therapeutic angiogenesis and tissue regeneration. Although previous reviews have focused primarily on revascularization outcomes after MSC treatments of CLTI with less attention given to their effects on wound healing, here we review advances in pre-clinical and clinical studies related to specific effects of MSC-based therapeutics upon ischemic non-healing wounds associated with CLTI.