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.

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).

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.

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).

Resveratrol derivative excited postsynaptic potentiation specifically via PKCß-NMDA receptor mediation.

Several decades have passed since resveratrol (RSV) was first identified in red wine. Researchers have reported the pleiotropic anti-oxidant, anti-inflammatory, anti-cancer, anti-aging, and neuronal protective effects of resveratrol and its glycosylated derivative. However, few studies have distinguished the minute differences in the properties between resveratrol and its glycosylated derivative in terms of synaptic plasticity. As an abundant natural product of glycosylated resveratrol, the derivative 2,3,4',5-tetrahydroxystilbene-2-O-ß-d-glucoside (TSG) has been determined to be a better option for long-term potentiation (LTP) in the hippocampus under physiological and pathological conditions than resveratrol. TSG, as well as its parent molecule RSV, could elicit early-LTP and recover fast excitatory postsynaptic potentials (EPSPs) in the hippocampus. Using various modalities, including pre- and post-whole-cell patch clamping techniques in the calyx of Held, pharmacological inhibition of the N-methyl-d-aspartic acid receptor (NMDAr) and the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAr) as well as protein kinase C (PKC) activation, we demonstrated that TSG, unlike RSV, could merely promote NMDA-mediated EPSC via PKCß cascade. Our results provide new knowledge that glycosylation of resveratrol could significantly improve its specificity in promoting sole NMDAr mediation of EPSPs, in addition to improving solubility and resistance against oxidation in vivo. These observations could contribute to further exploration of pharmaceutical evaluation of glycosylated stilbene in the future.

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).

Caballeronia ginsengisoli sp. nov., isolated from ginseng cultivating soil.

A Gram-stain-negative, strictly aerobic, non-motile, ivory colored and rod-shaped bacterium (designated Gsoil 652T) isolated from ginseng cultivating soil, was characterized using a polyphasic approach to clarify its taxonomic position. Strain Gsoil 652T was observed to grow optimally at 30 °C and at pH 7.0 on R2A agar medium. Phylogenetic analysis, based on 16S rRNA gene sequences similarities, indicated that Gsoil 652T belongs to the genus Caballeronia of the family Burkholderiaceae and was most closely related to Caballeronia choica LMG 22940T (98.9%), Caballeronia udeis LMG 27134T (98.9%), Caballeronia sordidicola LMG 22029T (98.2%) and Caballeronia humi LMG 22934T (98.1%). The DNA G+C content was 62.1 mol% and Q-8 was the major isoprenoid quinone. The main polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, unidentified aminophospholipid, and unidentified phospholipid. The predominant fatty acids were C16:0, C17:0 cyclo and C19:0 cyclo ω8c. The DNA-DNA relatedness value between strain Gsoil 652T and closely related type strains of Caballeronia species were less than 36.0%. Moreover, strain Gsoil 652T could be distinguished phenotypically from the recognized species of the genus Caballeronia. The novel isolate, therefore, represents a novel species, for which the name Caballeronia ginsengisoli sp. nov. is proposed, with the type strain Gsoil 652T (= KACC 19441T = LMG 30326T).

Sphingomonas panacisoli sp. nov., bacterium isolated from soil in South Korea.

A newly isolated bacterial strain designated as HKS19 was isolated from a ginseng cultivation soil sample collected in South Korea. Cells of the strain HKS19 were Gram-stain-negative, rod, oval-shaped and they formed yellow colonies when grown on R2A agar at 30 °C. HKS19 showed the highest 16S rRNA gene sequence similarity (98.6%) with Sphingomonas asaccharolytica NBRC 15499T. Its growth was observed at 10-37 °C (optimum 30 °C), pH 6-9 (optimum pH 7), and in the presence of 0-1% NaCl (optimum 0%). The genome size of HKS19 was 3.4 Mb and the G+C content was 65.1 mol%. The main polar lipid of strain HKS19 was diphosphatidylglycerol (DPG), the predominant respiratory quinone was Q-10 and the major fatty acids were a summed feature 8 (C18 : 1 ω6c / C18 : 1 ω7c) and C16 : 0. Based on the phylogenetic, genotypic, phenotypic and chemotaxonomic analysis, strain HKS19 represents a newly isolated species of the genus Sphingomonas, for which the name Sphingomonas panacisoli is proposed. The type strain is HKS19T (=KACC 18881T=LMG 29564 T).

PTEN-Induced Putative Kinase 1 (PINK1)/Parkin-Mediated Mitophagy Protects PC12 Cells Against Cisplatin-Induced Neurotoxicity.

BACKGROUND The pathogenesis of chemotherapy-induced neuropathy, a dose-dependent adverse effect of cisplatin, involves mitochondrial dysfunction. PTEN-induced putative kinase 1 (PINK1)/Parkin-mediated mitophagy removes damaged mitochondria under various pathological conditions. The objective of this study was to determine mitophagy status and its effects on mitochondrial function and neuronal cell damage after cisplatin treatment using an in vitro model of cisplatin-induced neurotoxicity. MATERIAL AND METHODS PC12 cells were transfected with Parkin or Parkin siRNA using lentiviral particles and Lipofectamine 3000™, respectively, and then were exposed to 10 µM cisplatin. The expression of autophagic proteins was measured by Western blot analysis. Mitophagy in PC12 cells was detected by confocal microscopy analysis of mitochondria-lysosomes colocalization and autophagic flux. The effects of PINK1/Parkin-mediated mitophagy on cisplatin-induced neurotoxicity were assessed via mitochondrial function, neuritic length, nuclear diameter, and apoptosis. RESULTS Cisplatin activated PINK1/Parkin-mediated mitophagy in PC12 cells. Autophagic flux analysis revealed that cisplatin inhibits the late stage of the autophagic process. The knockdown of Parkin suppressed cisplatin-induced mitophagy, aggravating cisplatin-induced depolarization of mitochondria, cellular ATP deficits, reactive oxygen species outburst, neuritic shortening, nuclear diameter reduction, and apoptosis, while Parkin overexpression enhanced mitophagy and reversed these effects. CONCLUSIONS PINK1/Parkin-regulated mitophagy can protect against cisplatin-related neurotoxicity, suggesting therapeutic enhancement of mitophagy as a potential intervention for cisplatin-induced peripheral neuropathies. The interference of cisplatin with autophagosome-lysosome fusion may be partly responsible for cisplatin-induced neurotoxicity.

Flavobacterium hankyongi sp. nov., isolated from activated sludge.

A Gram-stain-negative, aerobic, non-motile and rod-shaped bacterium, designated strain KTCe-4T, was isolated from activated sludge. Based on 16S rRNA gene sequencing and phylogenetic analysis, the novel isolate was found to belong to the genus Flavobacterium and was most closely related to Flavobacteriumterrae DSM 18829T (97.8 %), Flavobacteriumvireti THG-SM1T (97.8 %), Flavobacteriumbrevivitae TTM-43T (97.4 %) and shared <96.4 % sequence similarity to the other members of the genus. Strain KTCe-4T contained MK-6 as the predominant isoprenoid quinone and iso-C15 : 0, iso-C15 : 0 G, iso-C15 : 0 3-OH, iso-C17 : 0 3-OH and iso-C17 : 1ω9c, as the major fatty acids. The major polar lipids were phosphatidylethanolamine, two unidentified polar lipids and one unknown amino lipid. The DNA-DNA relatedness values of strain KTCe-4T with respect to type strains of recognized species of the genus Flavobacterium were less than 70 %. Based on 16S rRNA gene sequencing, low values of DNA-DNA hybridization and polyphasic taxonomic analysis, strain KTCe-4T represents a novel species within the genus Flavobacterium, for which the name Flavobacterium hankyongi sp. nov. is proposed. The type strain of Flavobacterium hankyongi is strain KTCe-4T (=KACC 16613T=JCM 18198T).

Genome-wide analysis of synonymous codon usage in Huaiyangshan virus and other bunyaviruses.

Huaiyangshan virus (HYSV) is a newly discovered bunyavirus, which is transmitted by ticks and causes hemorrhagic fever-like illness in human. The interplay of codon usage among viruses and their hosts is expected to affect viral survival, evasion from host's immune system and evolution. However, little is known about the codon usage in HYSV genome. In the present study, we analyzed synonymous codon usage in 120 available full-length HYSV sequences and performed a comparative analysis of synonymous codon usage patterns in HYSV and 42 other bunyaviruses. The relative synonymous codon usage (RSCU) analysis showed that the preferred synonymous codons were G/C-ended. A comparative analysis of RSCU between HYSV and its hosts reflected that codon usage patterns of HYSV were mostly coincident with that of its hosts. Our data suggested that although mutational bias dominated codon usage, patterns of codon usage in HYSV were also under the influence of nature selection. Phylogenetic analysis based on RSCU values across different HYSV strains and 42 other bunyaviruses suggested that codon usage pattern in HYSV was the most similar with that of Uukuniemi virus among these bunyaviruses and that viruses belonged to Phlebovirus showed a diversity of codon usage patterns.

[Impact of morphine on the reproductivity of male rats].

OBJECTIVE: To explore the effect of morphine on male reproductive ability and its mechanisms in the rat model of morphine tolerance. METHODS: Twenty male SD rats were equally randomized to groups I (control) and II (morphine tolerance). On the 1st day, the basic paw withdrawal thermal latency (PWTL) was obtained from all the rats followed by subcutaneous injection of morphine at 10 mg/kg and then calculation of the percentage of the maximal possible effect (MPE) at 30 min after administration. On the 2nd day, the rats of group I were injected subcutaneously with saline and those of group I with morphine at 10 mg/kg bid for 7 days. Then all the rats were killed after behavioral tests and their testes and epididymides harvested for sperm counting and determina- tion of the expressions of Bax and Caspase-3 by immunohistochemistry. RESULTS: On the 1st day, no obvious differences were ob- served between the two groups in the basic PWTL or the percentage of MPE. On the 7th day, the percentage of MPE was significantly decreased in group II as compared with group I (P < 0.05), while the basic PWTL showed no marked difference between the two groups. Group II also exhibited a significantly reduced epididymal perm count (P < 0.05) and remarkably upregulated expressions of Bax and Caspase-3 in comparison with group I. CONCLUSION: Morphine might increase testicular cell apoptosis and reduce sperm concentration by upregulating the expressions of Bax and Caspase-3 in the rat model of morphine tolerance.

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.

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.

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.

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.

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.

Gene silencing efficiency and INF-ß induction effects of splicing miRNA 155-based artificial miRNA with pre-miRNA stem-loop structures.

Artificial microRNA (miRNA) expression vectors have been developed and used for RNA interference. The secondary structure of artificial miRNA is important for RNA interference efficacy. We designed two groups of six artificial splicing miRNA 155-based miRNAs (SM155-based miRNAs) with the same target in the coding region or 3' UTR of a target gene and studied their RNA silencing efficiency and interferon ß (IFN-ß) induction effects. SM155-based miRNA with a mismatch at the +1 position and a bulge at the +11, +12 positions in a miRNA precursor stem-loop structure showed the highest gene silencing efficiency and lowest IFN-ß induction effect (increased IFN-ß mRNA level by 10% in both target cases), regardless of the specificity of the target sequence, suggesting that pSM155-based miRNA with this design could be a valuable miRNA expression vector.