Short-term effect of low-dose roxadustat combined with erythropoiesis-stimulating agent treatment for erythropoietin-resistant anemia in patients undergoing maintenance hemodialysis.

Background: Erythropoietin resistance is present in some patients with chronic kidney disease, especially in those undergoing hemodialysis, and is often treated using roxadustat rather than iron supplements and erythropoiesis-stimulating agents (ESAs). However, some patients cannot afford full doses of roxadustat. This retrospective study investigated the efficacy of low-dose roxadustat combined with recombinant human erythropoietin (rhuEPO) therapy in 39 patients with erythropoietin-resistant renal anemia undergoing maintenance hemodialysis (3-4 sessions/week). Methods: The ability of the combination of low-dose roxadustat and rhuEPO to increase the hemoglobin concentration over 12 weeks was assessed. Markers of iron metabolism were evaluated. Eligible adults received 50-60% of the recommended dose of roxadustat and higher doses of rhuEPO. Results: The mean hemoglobin level increased from 77.67 ± 11.18 g/dL to 92.0 ± 8.35 g/dL after treatment, and the hemoglobin response rate increased to 72%. The mean hematocrit level significantly increased from 24.26 ± 3.99% to 30.04 ± 3.69%. The soluble transferrin receptor level increased (27.29 ± 13.60 mg/L to 38.09 ± 12.78 mg/L), while the total iron binding capacity (49.22 ± 11.29 mg/L to 43.91 ± 12.88 mg/L) and ferritin level (171.05 ± 54.75 ng/mL to 140.83 ± 42.03 ng/mL) decreased. Conclusion: Therefore, in patients with ESA-resistant anemia who are undergoing hemodialysis, the combination of low-dose roxadustat and rhuEPO effectively improves renal anemia and iron metabolism.

Hematopoietic stem cell transplantation from an infected SARS-CoV2 haploidentical donor: A case report.

Introduction: We report a case of an adult hematopoietic stem cell donor who developed active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the donation of stem cells, the final transplantation was successfully completed without SARS-CoV-2 transmission. Case report: We report on a 34-year-old female diagnosed with acute lymphoblastic leukemia who underwent hemiploid hematopoietic stem cell transplantation (HSCT). Both patient and donor received three doses of inactivated SARS-CoV-2 vaccine before transplantation. PB-HSC was collected by the donor during the process of infection with SARS-CoV-2 (mild), and the patient did not show symptoms related to SARS-CoV-2 after transplantation. Nucleic acid and antigen were negative in regular tests. Conclusion: In the context of the current Omicron epidemic and high vaccination rate in the population, it is feasible to receive PB-HSC from infected donors even for immunocompromised patients. This also provides some references for our later donor selection.

FN1 and TGFBI are key biomarkers of macrophage immune injury in diabetic kidney disease.

The pathogenesis of diabetic kidney disease (DKD) is complex, and the existing treatment methods cannot control disease progression well. Macrophages play an important role in the development of DKD. This study aimed to search for biomarkers involved in immune injury induced by macrophages in DKD. The GSE96804 dataset was downloaded and analyzed by the CIBERSORT algorithm to understand the differential infiltration of macrophages between DKD and normal controls. Weighted gene co-expression network analysis was used to explore the correlation between gene expression modules and macrophages in renal tissue of DKD patients. Protein-protein interaction network and machine learning algorithm were used to screen the hub genes in the key modules. Subsequently, the GSE30528 dataset was used to further validate the expression of hub genes and analyze the diagnostic effect by the receiver operating characteristic curve. The clinical data were applied to explore the prognostic significance of hub genes. CIBERSORT analysis showed that macrophages increased significantly in DKD renal tissue samples. A total of ten modules were generated by weighted gene co-expression network analysis, of which the blue module was closely associated with macrophages. The blue module mainly played an important role in biological processes such as immune response and fibrosis. Fibronectin 1 (FN1) and transforming growth factor beta induced (TGFBI) were identified as hub genes of DKD patients. Receiver operating characteristic curve analysis was performed in the test cohort: FN1 and TGFBI had larger area under the curve values (0.99 and 0.88, respectively). Clinical validation showed that 2 hub genes were negatively correlated with the estimated glomerular filtration rate in DKD patients. In addition, FN1 and TGFBI showed a strong positive correlation with macrophage alternative activation. FN1 and TGFBI are promising biomarkers for the diagnosis and treatment of DKD patients, which may participate in immune response and fibrosis induced by macrophages.

Systematic analysis of the necroptosis index in pan-cancer and classification in discriminating the prognosis and immunotherapy responses of 1716 glioma patients.

Necroptosis is a programmed form of necrotic cell death that serves as a host gatekeeper for defense against invasion by certain pathogens. Previous studies have uncovered the essential role of necroptosis in tumor progression and implied the potential for novel therapies targeting necroptosis. However, no comprehensive analysis of multi-omics data has been conducted to better understand the relationship between necroptosis and tumor. We developed the necroptosis index (NI) to uncover the effect of necroptosis in most cancers. NI not only correlated with clinical characteristics of multiple tumors, but also could influence drug sensitivity in glioma. Based on necroptosis-related differentially expressed genes, the consensus clustering was used to classify glioma patients into two NI subgroups. Then, we revealed NI subgroup I were more sensitive to immunotherapy, particularly anti-PD1 therapy. This new NI-based classification may have prospective predictive factors for prognosis and guide physicians in prioritizing immunotherapy for potential responders.

Antidepressant effects of repeated s-ketamine administration as NMDAR Antagonist: Involvement of CaMKIIα and mTOR signaling in the hippocampus of CUMS mice.

With the approval of s-ketamine nasal spray as a novel antidepressant, its robust antidepressant effects have been intensively examined in clinical trials. However, the therapeutic efficacy and mechanisms of repeated intermittent drug administration remain unclear. In the present study, we applied a classic chronic unpredictable mild stress (CUMS) model to induce depressive-like behaviors of mice and evaluated the role of repeated s-ketamine administration (10 mg/kg, 7 consecutive days) in ameliorating depressive-like behaviors and modulating related molecular pathways. A battery of behavioral tests were performed to assess CUMS-induced depression. The protein expressions of GluN1, GluN2A, GluN2B, GluR1, CaMKIIα, phosphorylated CaMKIIα (p-CaMKIIα), BDNF, TrkB, phosphorylated TrkB (p-TrkB), mTOR, and phosphorylated mTOR (p-mTOR) as well as modification of synaptic ultrastructure was identified in hippocampal tissues. It turned out that s-ketamine manifested evident antidepressant effects with improved synaptic plasticity. Meanwhile, the results suggested that s-ketamine could differentially modulate glutamate receptors with upregulated GluN1 and GluR1 levels and downregulated GluN2B levels. CUMS-induced elevation of CaMKIIα phosphorylation and decline of BDNF, TrkB phosphorylation and mTOR could also be reversed through s-ketamine treatment. Together, our study provided evidence that selectively modulated glutamate receptors as well as CaMKIIα and mTOR signaling were involved in repeated s-ketamine administration.

Sevoflurane Preconditioning Alleviates Posttraumatic Stress Disorder-Induced Apoptosis in the Hippocampus via the EZH2-Regulated Akt/mTOR Axis and Improves Synaptic Plasticity.

Posttraumatic stress disorder (PTSD) is a persistent and severe psychological and mental disorder resulting from experiences of serious trauma or stress and is suffered by many individuals. Previous studies have shown that pretreatment with sevoflurane is efficient in reducing the incidence of PTSD. However, we require a more comprehensive understanding of the specific mechanisms by which sevoflurane works. Enhancer of zeste homolog 2 (EZH2) has been reported to be regulated by sevoflurane, and to improve patient cognition. In this study, we aimed to explore the mechanisms of sevoflurane and the role of EZH2 in PTSD cases. We explored the effects of sevoflurane and EPZ-6438 (inhibitor of EZH2) on rat behavior, followed by an investigation of EZH2 mRNA and protein expression. The effects of sevoflurane and EZH2 on neuronal survival were assessed by western blotting and TUNEL staining, while western blotting was used to examine the expression of PSD95 and the AKT/mTOR proteins. Sevoflurane preconditioning restored EZH2 expression and significantly inhibited apoptosis by regulating phosphorylation of the AKT/mTOR pathway. Synaptic plasticity was also significantly improved. These results suggest that pretreatment with sevoflurane could play an important role in PTSD prevention by regulating EZH2 expression.

Sphingomonas cremea sp. nov., isolated from ginseng soil.

A novel Gram-stain-negative, aerobic, rod-shaped, non-motile, cream-coloured strain (G124T) was isolated from ginseng soil collected in Yeongju, Republic of Korea. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain G124T belongs to a distinct lineage within the genus Sphingomonas (family Sphingomonadaceae, order Sphingomonadales and class Alphaproteobacteria). Strain G124T was closely related to Sphingomonas rhizophila THG-T61T (98.5 % 16S rRNA gene sequence similarity), Sphingomonas mesophila SYSUP0001T (98.3 %), Sphingomonas edaphi DAC4T (97.6 %) and Sphingomonas jaspsi TDMA-16T (97.6 %). The strain contained ubiquinone 10 as the major respiratory quinone. The major polar lipid profile of strain G124T comprised phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine and sphingoglycolipids. The predominant cellular fatty acids of strain G124T were summed feature 8 (C18 : 1 ω7c/C18 : 1 ω6c; 33.4 %), summed feature 3 (C16 : 1 ω6c/C16 : 1 ω7c; 27.2 %) and C16 : 0 (18.3 %). The genome size of strain G124T was 2 549 305 bp. The genomic DNA G+C content is 62.0 mol%. The average nucleotide identity and digital DNA-DNA hybridization values between strain G124T and other Sphingomonas species were in the range of 71.2-75.9 % and 18.7-19.9 %, respectively. Based on the polyphasic analysis such as biochemical, phylogenetic and chemotaxonomic characteristics, strain G124T represents a novel species of the genus Sphingomonas, for which the name Sphingomonas cremea sp. nov. is proposed. The type strain is G124T (=KACC 21691T=LMG 31729T).

Study of 60 Adult Patients to Compare Standard Postoperative Clinical Assessment with Train-of-Four Ratio ≥0.9 on Patient Outcomes Using Postoperative Spirometry and Neuromuscular Function Measurements Following Extubation.

BACKGROUND Postoperative tracheal extubation requires optimal timing to ensure patient safety and normal muscle function. The train-of-four ratio (TOFR) of the fourth muscle response compared with the first indicates a non-depolarizing neuromuscular block, and a ratio ≥0.9 can be used as an objective measurement of neuromuscular reversal. This study of 60 adult patients who underwent elective surgery with general anesthesia that included the neuromuscular blocking agent cisatracurium aimed to compare standard postoperative clinical assessment with the TOFR ≥0.9 on patient outcomes using postoperative neuromuscular function assessed by grip strength and ability to sit up unaided and spirometry measurements following extubation. MATERIAL AND METHODS The 30 patients extubated postoperatively in the TOF group were required to have a TOFR ≥0.9, while the 30 patients in the clinical assessment group were awake and following simple commands and had a 5-second head lift and spontaneous breathing with acceptable oxygenation. The main outcomes were the incentive spirometry and grip strength and ability to sit up unaided measured at 10, 30, 50 min and 24 h after extubation. RESULTS The groups had no difference in recovery path of incentive spirometry volume (P=0.072) and no difference in postoperative incentive spirometry decrease from baseline except at 10 min after extubation (P=0.005). There was no difference in handgrip strength and independent sitting between groups. CONCLUSIONS The findings showed that using the TOF ratio ≥0.9 before extubation did not improve early postoperative strength quantified by spirometry volume, handgrip strength, and proportion of unaided sitting.

Mesenchymal Stem Cell-Derived Exosomes Ameliorate Diabetic Kidney Disease Through the NLRP3 Signaling Pathway.

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease worldwide. Exosomes (Exo) derived from human umbilical cord mesenchymal stem cells (HUC-MSCs) have been demonstrated to be an effective therapy for DKD, but the underlying mechanisms of this action remain poorly defined. We investigated the association of DKD with inflammasome activation and the pathophysiological relevance of Exo-mediated inflammation relief as well as damage repair in this progression. We co-cultured podocytes and HUC-MSCs derived Exo (MSCs-Exo) under high glucose (HG) and injected MSCs-Exo into diabetic mice, then we detected the NLRP3 inflammasome both in vitro and in vivo. We found that HG reduced the viability of podocytes, activated the NLRP3 signaling pathway and increased inflammation in podocytes and diabetic mice. MSCs-Exo attenuated the inflammation, including the expression of IL-6, IL-1ß, IL-18, TNF-α; depressed the activation of NLRP3 signaling pathway in podocytes under HG and diabetic mice, ameliorated kidney injury. Furthermore, miR-22-3p, which is relatively highly expressed miRNAs in exosomes of MSCs, may be the key point in this progress, by suppressing the expression of its known target, NLRP3. Knocking down miR-22-3p from MSCs-Exo abolished their anti-inflammation activity and beneficial function both in vitro and in vivo. Collectively, our results have demonstrated that exosomes transferring miR-22-3p protected the podocytes and diabetic mice from inflammation by mediating NLRP3 inflammasome, indicating that MSC-derived exosomes may be a promising therapeutic cell-free strategy for DKD.

Nocardioides panacis sp. nov., isolated from soil of a ginseng field.

A bacterial strain designated as G188T was isolated from ginseng field soil in the Republic of Korea. Phylogenetic analysis of 16S rRNA gene sequences showed that strain G188T formed a distinct lineage within the genus Nocardioides, family Nocardioidaceae, order Propionibacteriales. Sequence similarity revealed that strain G188T was most closely related to Nocardioides iriomotensis IR27-S3T (97.7 % 16S rRNA similarity). The genome size of strain G188T was 4 901 775 bp, and the genomic DNA G+C content was 72.3 mol%. The average nucleotide identity and DNA-DNA hybridization values with other Nocardioides species were less than 75.6 and 20.1 %, respectively. The main fatty acids of strain G188T were C17 : 0, C17 : 1 ω8c and iso-C16 : 0. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, and phosphatidylinositol, and the major respiratory quinone was menaquinone 8, supporting that strain G188T was affiliated with the genus Nocardioides. Based on biochemical, chemotaxonomic and phylogenetic analyses, the novel species Nocardioides panacis G188T (KACC 21695T=LMG 31733T) is proposed.

Autophagy: A New Mechanism for Esketamine as a Depression Therapeutic.

Depression is a serious physical and mental disease, with major depressive disorder (MDD) being a hard-to-treat, life-threatening form of the condition. Currently, esketamine (ESK) is used in the clinical treatment of MDD, but the drug mechanisms continue to be unclear. In this study, we explored the therapeutic efficacy of ESK against lipopolysaccharide (LPS)-induced neuroinflammatory, autophagic, and depressive symptoms and the possible mechanisms behind them. Our study demonstrated that LPS increased cytokine levels (TNF-α, IL-1ß, IL-6), induced neuroinflammation, led to increased levels of autophagy markers, and enhanced autophagy activation, which ultimately caused depressive symptoms in mouse models. ESK inhibited autophagy via the mTOR-BDNF signaling pathway and significantly alleviated the adverse effects induced by LPS, mainly in the form of reduced levels of cytokines, apoptotic factors, and autophagic markers; elevated BDNF levels; and improved depression-like behavior. Furthermore, we were interested to know if ESK in combination with other autophagy inhibitors would have a better antidepressant effect, and we chose the autophagy inhibitor 3-MA for this attempt. Interestingly, the use of 3-MA did not attenuate or even enhance the therapeutic effect of ESK. The results suggest that, in the LPS-induced depression models, ESK conveyed an antidepressant effect via the inhibition of autophagy through the mTOR-BDNF pathway.

Hanamia caeni gen. nov., sp. nov., a Member of the Family Chitinophagaceae Isolated from Activated Sludge in Korea.

A novel Gram-stain-negative, aerobic, yellowish-pigmented, non-motile, rod-shaped bacterial strain, designated strain BO-59T, was isolated from the activated sludge of a wastewater treatment plant in Hanam City, South Korea. Phylogenetic study based on the 16S rRNA gene sequence positioned BO-59T in a distinct lineage in the family Chitinophagaceae, sharing less than 92.8% sequence similarity with members of the closely related genera Ferruginibacter, Flavitalea, Pseudoflavitalea, Flavisolibacter, Niastella, and Terrimonas. Phylogenomic- and genomic relatedness analyses revealed that strain BO-59T is clearly distinguished from other genera in the family Chitinophagaceae by average nucleotide identity < 66.9%) and the genome-to-genome distance (< 29.5%) values. The strain BO-59T contained MK-7 as the predominant quinone, and iso-C15:0, iso-C17:0 3OH, and iso-C15:1 G as major fatty acids (> 10%). The DNA G + C content was 39.1 mol% based on genome sequence analysis. The polar lipids of strain BO-59T were phosphatidylethanolamine, an unidentified aminophospholipid and three unidentified polar lipids. 16S rRNA gene sequence similarity, physiological, and biochemical characteristics indicated that strain BO-59T represents a novel species of a new genus, for which the name Hanamia caeni gen. nov., sp. nov. is proposed. The type strain is BO-59T (= KACC 19646T = LMG 30865 T).

Interplay between autophagy and Sindbis virus in cells derived from key arbovirus vectors, Aedes albopictus and Aedes aegypti mosquitoes.

Aedes albopictus and Aedes aegypti are two species of Aedes mosquitoes which transmit multiple arboviruses causing serious diseases in human. Intriguingly, infection of arbovirus in both Aedes mosquitoes does not cause dramatic pathology, indicating that both mosquitoes have evolved mechanisms to tolerate persistent infection and restrict viral replication to nonpathogenic levels. Therefore, understanding how these mosquitoes interact with viruses would help to find targets for controlling the related mosquito-borne diseases. Autophagy is a conserved cellular recycling process functioning in maintenance of cellular homeostasis and recirculation of cytoplasmic materials under stressful conditions. Autophagy also acts as a cellular defense mechanism against viral infection. It is known that autophagy plays important roles in the replication of several Aedes mosquito-borne viruses in mammalian systems. However, little information is available regarding the role of autophagy in replication of those viruses in their primary vector, Aedes mosquitoes. This study found that interaction between autophagy and replication of Sindbis virus (SINV) occurred in Aedes albopictus C6/36 cells and Ae. aegypti Aag2 cells. Moreover, it discovered that the patterns of interaction between autophagy and SINV replication are different in C6/36 cells and Aag2 cells. It was shown that replication of SINV induced complete autophagy in C6/36 cells but suppressed autophagy in Aag2 cells. Moreover, induction of autophagy by rapamycin treatment restricted SINV replication in C6/36 cells but promoted SINV replication in Aag2 cells. Consistent with this, suppression of autophagy by down regulation of Atg8 promoted SINV replication in C6/36 cells but restricted SINV replication in Aag2 cells. It was also found that, in both C6/36 and Aag2 cells, interaction between autophagy and SINV replication occurred after viral entry and prior to viral assembly. Collectively, this work demonstrated that SINV replication manipulated autophagy in Aedes mosquito cells and provided strong evidence of the role autophagy played in viral replication in Aedes mosquitoes. The findings have laid a foundation to elucidate the correlation between autophagy and arbovirus replication in Aedes mosquitoes and could help to understand the difference in viral transmission capacity of the two Aedes mosquitoes, Ae. albopictus and Ae. aegypti.

Quantitative Proteomics Analysis of Susceptibility and Resilience to Stress in a Rat model of PTSD.

Posttraumatic stress disorder (PTSD) is a prevalent psychiatric disorder and sometimes deadly consequence of exposure to severe psychological trauma. However, there has been little known about the definitive molecular changes involved in determining vulnerability to PTSD. In the current study, we used proteomics to quantify protein changes in the hippocampus of foot shocks rats. A total of 6151 proteins were quantified and 97 proteins were significantly differentially expressed. The protein-protein interaction (PPI) analysis showed that oxidation-reduction process and glutathione homeostasis may be the potential key progress of being vulnerable to PTSD. The Gene Ontology analysis revealed enriched GO terms in the protein groups of Susceptible group vs Control group rats for glutathione binding,oligopeptide binding,modified amino acid binding,and glutathione transferase activity for their molecular functions (MF) and in the process of cellular response to toxic substance,xenobiotic metabolic process, urea metabolic process, and response to drug for the biological process (BP).SIGNIFICANCE:In recent years, there has been a growing interest in mental illness associated with trauma exposure. We found that stress susceptibility was associated with increased expression of arginase 1 indicated as a potential treatment target. Our results also proposed that carbonic anhydrases 3 could be a biomarker for the development of PTSD. This research helps to explain the potential molecular mechanism in PTSD and supply a new method for ameliorating PTSD.

Human umbilical cord mesenchymal stem cells attenuate podocyte injury under high glucose via TLR2 and TLR4 signaling.

AIMS: This research aimed to investigate the effects of high glucose (HG) on the innate immunity of podocytes and diabetic nephropathy (DN) mice via Toll like receptor (TLR) signaling, and explore the protective effectsof human umbilical cord mesenchymal stem cells (HUC-MSCs) on this process. METHODS: HUC-MSCs obtained from human umbilical cord were cocultured with podocytes and transplanted into DN mice. Flow cytometry, CCK-8assay, ELISA, western blot analysis, periodicacid-schiff, masson, immunohistochemistry and immunofluorescence staining was used to detect the inflammation, TLR signaling, physical, biochemical and morphological parameters in podocytes and DN mice. RESULTS: HG reduced the viability of podocytes, activated TLR2 and TLR4 signaling pathway and increased the expression of inflammatory cytokines such as IL-6, IL-1ß, TNF-α, and MCP-1 in podocytes and DN mice. However, HUC-MSCs decreased the inflammation and restrained the TLR signaling pathway caused by HG in vitro and in vivo. Furthermore the rhHGF decreased the expression of TLR2 and TLR4 while the blockade of HGF increased the expression of TLR2 and TLR4 in podocytes. CONCLUSIONS: HUC-MSCs have benefits to the podocytes under HG and the progression of DN by inhibiting TLR signaling pathway and depressing the inflammation. HUC-MSCs may be a therapeutic strategy for treating patients with DN.

Systematic identification of autophagy-related proteins in Aedes albopictus.

Autophagy is a conserved cellular process playing a role in maintenance of cellular homeostasis and response to changing nutrient conditions via degradation and recirculation of cellular redundant components. Autophagy-related proteins (Atg) play important function in autophagy pathway. Aedes albopictus mosquito is an effective vector transmitting multiple viruses which cause serious human diseases. Moreover, Aedes albopictus mosquito is becoming a serious threat to human health due to its widening distribution in recent years and thus worth of more research attention. It was reported that autophagy might play a role in viral infection in Aedes mosquito. To better understand the interaction between autophagy and arbovirus infection in mosquito system, it is necessary to identify autophagy pathway in the system. However, autophagy in Aedes albopictus mosquito is still poorly understood so far. We recently identified AaAtg8, the first Atg protein reported in Aedes albopictus mosquito. This work further identified twelve atg genes in Aedes albopictus mosquito. Sequence and phylogenetic analysis of the twelve atg genes were performed. Expression profiles of all the twelve Aaatg genes in different developmental stages and genders of Aedes albopictus mosquito were conducted. Effects of chemicals inhibiting or inducing autophagy on the levels of eight identified AaAtg proteins were examined. The function of two identified AaAtg proteins AaAtg6 and AaAtg16 and their response to arbovirus SINV infection were studied preliminarily. Taken together, this work systematically identified Aedes albopictus atg genes and provided basic information which might help to elucidate the autophagy pathway and the role of autophagy in arbovirus infection in Aedes mosquito system.

Induced pluripotent stem cell-derived neural progenitor cell transplantation promotes regeneration and functional recovery after post-traumatic stress disorder in rats.

Post-traumatic stress disorder (PTSD) is a mental disorder characterized by hippocampal neuron loss and cognitive dysfunction. The aim of the present study was to investigate the potential functional outcomes of transplantation of induced pluripotent stem cell-derived neural progenitor cells (iPSC-NPCs) for treating PTSD. Human induced pluripotent stem cell (iPSCs), differentiated into neural progenitor cells (NPCs) in vitro, were transplanted into the brain of rat. Following iPSC-NPCs transplantation, cognitive function was determined. The open field test and fear condition test indicated that long-term iPSC-NPCs transplantation ameliorated cognitive dysfunction and reduced freezing time in PTSD rats. Following testing, the brain of rat was analyzed using immunocytochemistry and immunofluorescence. The results revealed that iPSC-NPCs differentiated into neurons replacing the loss of hippocampus neurons, and iPSC-NPCs transplantation showed higher expression of glial fibrillary acidic protein (GFAP) and increased number of NeuN compared with the control group. Moreover, western blot analysis suggested enhanced expression of brain-derived neurotrophic factor (BDNF) in hippocampus tissue of iPSC-NPCs transplanted rats in comparison to the PBS group. Collectively, these findings showed that iPSC-NPCs could promote regeneration and motor function recovery in PTSD model.

Nocardioides convexus sp. nov. and Nocardioides anomalus sp. nov., isolated from soil and mineral water.

Two bacterial strains designated as W3-2-3T and HKS04T were isolated from mineral water and a soil sample, respectively, in the Republic of Korea. The 16S rRNA genes of the two strains shared a sequence similarity of 93.5 %. Phylogenetic analysis based on 16S rRNA gene sequences showed that strains W3-2-3T and HKS04T formed a distinct lineage within the genus Nocardioides of the family Nocardioidaceae (order Propionibacteriales). The closely related species of strain W3-2-3T were Nocardioides albidus (98.9 %), Nocardioides caeni (98.8 %), Nocardioides kongjuensis (98.6 %), Nocardioides aromaticivorans (98.5 %), Nocardioides nitrophenolicus (98.4 %), Nocardioides flava (98.2 %) and Nocardioides ginsengisoli (98.1 %). The closest species of strain HKS04T was Nocardioides halotolerans (98.7 %). The genome sizes of strains W3-2-3T and HKS04T were 4741198 and 5 120341 bp, respectively. The genomic DNA G+C contents of strains W3-2-3T and HKS04T were 73.3 and 72.1 mol%, respectively. The main fatty acids of strain W3-2-3T were C17:1 ω6c and iso-C16:0 and those of strain HKS04T were iso-C16:0 and iso-C16:0 H. The main polar lipids of both strains were diphosphatidylglycerol and phosphatidylglycerol and the predominant respiratory quinone was MK-8(H4), supporting the affiliation of these strains with the genus Nocardioides. Based on the results of biochemical, chemotaxonomic and phylogenetic analyses, two novel species, Nocardioides convexus W3-2-3T (KACC 21211T=LMG 31251T) and Nocardioides anomalus HKS04T (KACC 18879T=LMG 31249T), are proposed.

Devosia ginsengisoli sp. nov., isolated from ginseng cultivation soil.

A Gram-stain-negative, strictly aerobic, motile, ivory-coloured and rod-shaped bacterium (designated Gsoil 520T) isolated from ginseng cultivation soil was characterized by using a polyphasic approach to clarify its taxonomic position. Strain Gsoil 520T was observed to grow optimally at 30 °C and pH 7.0 on Reasoner's 2A agar medium. The results of phylogenetic analysis, based on 16S rRNA gene sequence similarities, indicated that Gsoil 520T belongs to the genus Devosia of the family Hyphomicrobiaceae and was most closely related to Devosia epidermidihirudinis E84T (98.0 %), Devosia yakushimensis Yak96BT (97.7 %), Devosia neptuniae J1T (97.7 %) and Devosia chinhatensis IPL18T (96.8 %). The complete genome of strain Gsoil 520T is a presumptive circular chromosome of 4 480 314 base pairs having G+C content of 63.7 mol%. A total of 4 354 genes, 4 303 CDS and 43 rRNA genes were assigned a putative function. The major isoprenoid quinone was Q-10. The main polar lipids were phosphatidylglycerol, diphosphatidylglycerol and two unidentified aminolipids (AL1 and AL3). The predominant fatty acids of strain Gsoil 520T were C18 : 1ω7c 11-methyl, C16 : 0 and C18 : 1ω7c/C18 : 1ω6c (summed feature 8) supporting the affiliation of strain Gsoil 520T to the genus Devosia. The low values of DNA-DNA hybridization distinguished strain Gsoil 520T from the recognized species of the genus Devosia. Thus, the novel isolate represents a novel species of the genus Devosia, for which the name Devosia ginsengisoli sp. nov. is proposed, with the type strain Gsoil 520T (=KACC 19440T=LMG 30329T).

Mesenchymal stem cells modified with angiotensin-converting enzyme 2 are superior for amelioration of glomerular fibrosis in diabetic nephropathy.

AIMS: This study aimed to detect the effect of angiotensin-converting enzyme (ACE) 2-modified mesenchymal stem cells (MSCs) on glomerular fibrosis in vitro and in vivo and investigate the underlying molecular mechanism. METHODS: MSCs transduced with the ACE2 gene (MSCs-ACE2) were cocultured with glomerular mesangial cells (GMCs) following Ang II stimulation. MSCs-ACE2 were transplanted into streptozotocin-induced diabetic rats. Physical, biochemical and morphological parameters were measured, and fibrotic indicators and renin-angiotensin system (RAS) components in GMCs and kidney tissues were assessed. RESULTS: The transduction efficiency of MSCs was as high as 85%. The modified MSCs secreted soluble ACE2 protein into the culture medium. After transplantation into rats with diabetes, MSCs-ACE2 targeted injured kidneys and enhanced local expression of ACE2. Compared with MSC treatment alone, MSC-ACE2 treatment was superior in reducing albuminuria and improving glomerulosclerosis. In vitro and in vivo, MSCs-ACE2 were more beneficial than MSCs alone in decreasing Ang II and increasing Ang1-7, thereby inhibiting the detrimental effects of Ang II accumulation by downregulating collagen I and fibronectin (FN) expression and inhibiting the transforming growth factor (TGF-ß)/Smad pathway. CONCLUSIONS: MSCs modified with ACE2 therapy have additional benefits to the progression of diabetic nephropathy (DN) by inhibiting renal RAS activation and reducing glomerular fibrosis.