HSP90ß shapes the fate of Th17 cells with the help of glycolysis-controlled methylation modification.

BACKGROUND AND PURPOSE: Ulcerative colitis (UC) is a refractory inflammatory disease associated with immune dysregulation. Elevated levels of heat shock protein (HSP) 90 in the ß but not α subtype were positively associated with disease status in UC patients. This study validated the possibility that pharmacological inhibition or reduction of HSP90ß would alleviate colitis, induced by dextran sulfate sodium, in mice and elucidated its mechanisms. EXPERIMENTAL APPROACH: Histopathological and biochemical analysis assessed disease severity, and bioinformatics and correlation analysis explained the association between the many immune cells and HSP90ß. Flow cytometry was used to analyse the homeostasis and transdifferentiation of Th17 and Treg cells. In vitro inhibition and adoptive transfer assays were used to investigate functions of the phenotypically transformed Th17 cells. Metabolomic analysis, DNA methylation detection and chromatin immunoprecipitation were used to explore these mechanisms. KEY RESULTS: The selective pharmacological inhibitor (HSP90ßi) and shHSP90ß significantly mitigated UC in mice and promoted transformation of Th17 to Treg cell phenotype, via Foxp3 transcription. The phenotypically-transformed Th17 cells by HSP90ßi or shHSP90ß were able to inhibit lymphocyte proliferation and colitis in mice. HSP90ßi and shHSP90ß selectively weakened glycolysis by stopping the direct association of HSP90ß and GLUT1, the key glucose transporter, to accelerate ubiquitination degradation of GLUT1, and enhance the methylation of Foxp3 CNS2 region. Then, the mediator path was identified as the "lactate-STAT5-TET2" cascade. CONCLUSION AND IMPLICATIONS: HSP90ß shapes the fate of Th17 cells via glycolysis-controlled methylation modification to affect UC progression, which provides a new therapeutic target for UC.

A clinical predictive model for pre-transplantation Klebsiella pneumoniae colonization and relevance for clinical outcomes in patients receiving allogeneic hematopoietic stem cell transplantation.

The purpose of this study is to establish a clinical prediction model to discriminate patients at high risk of Klebsiella pneumoniae (KP) colonization before allogeneic hematopoietic stem cell transplantation (allo-HSCT) and evaluate the impact of KP colonization on clinical outcomes after allo-HSCT. We retrospectively collected data from 2,157 consecutive patients receiving allo-HSCT between January 2018 and March 2022. KP colonization was defined as a positive test for KP from a pharyngeal or anal swab before allo-HSCT. Logistic regression was used to build a clinical prediction model. Cox regression analyses were performed to explore the effect of KP colonization on clinical outcomes. Among all the inpatients, 166 patients had KP colonization and 581 with no positive pathogenic finding before transplantation. Seven candidate predictors were entered into the final prediction model. The prediction model had an area under the curve of 0.775 (95% CI 0.723-0.828) in the derivation cohort and 0.846 (95% CI: 0.790-0.902) in the validation cohort. Statistically significantly different incidence rates were observed among patient groups with clinically predicted low, medium, and high risk for KP infection (P < 0.001). The presence of KP colonization delayed platelet engraftment (P < 0.001) and patients with KP colonization were more likely to develop KP bloodstream infections within 100 days after allo-HSCT (P < 0.0001). Patients with KP colonization had higher non-relapse mortality (P = 0.032), worse progression-free survival (P = 0.0027), and worse overall survival within 100 days after allo-HSCT (P = 0.013). Our findings suggest that increased awareness of risks associated with pre-transplantation bacterial colonization is warranted.IMPORTANCESeveral studies have identified that Klebsiella pneumoniae (KP) is among the most common and deadly pathogens for patients in hospital intensive care units and those receiving transplantation. However, there are currently no studies that evaluate the impact of KP colonization to patients undergoing allogeneic hematopoietic stem cell transplantation. Our results confirm that pre-existing KP colonization is relatively common in a hematology transplant ward setting and negatively affects post-transplantation prognosis. Our clinical prediction model for KP colonization can support early intervention in patients at high risk to avoid subsequent bloodstream infections and improve survival outcomes. Altogether, our data suggest that increased awareness of risks associated with pre-transplantation bacterial colonization is warranted. Future studies are needed to confirm these findings and to test early intervention strategies for patients at risk of complications from KP infection.

Effect of particle dispersion on electrochemical performance of Prussian blue analogues electrode materials for sodium ion batteries.

Prussian blue analogues (PBAs) have advantages such as high voltage and low cost, making them one kind of the promising positive electrode materials for sodium-ion batteries. Particle dispersion is a key physical parameter of electrode materials, and understanding its impact on electrochemical performance is a prerequisite for obtaining high-performance PBAs. In this article, two PBAs samples with different particle dispersion were synthesized through sodium citrate-assisted co-precipitation method by means of staying and stirring. The influence of particle dispersion on electrochemical performance was investigated through polarization curve and AC impedance tests. It was found that PBAs with well-dispersed particles exhibited excellent rate performance, with a capacity of ~120 mAh g-1 at 1 C rate and a capacity retention of 75 % after 100 cycles. The capacity retention rate could reach 63 % at 5 C rate, far higher than that of PBAs samples with poor particle dispersion. From the perspective of electrochemical kinetics analysis, it has been shown that PBAs with well-dispersed particles exhibit smaller electrochemical polarization and faster Na+ diffusion reaction kinetics, which are key factors in achieving excellent rate performance.

Risk Factors for Carbapenem-Resistant Enterobacteriaceae Colonization and the Effect on Clinical Outcomes and Prognosis in Allogeneic Hematopoietic Stem Cell Transplanted Patients.

Purpose: The current study assesses which are the main risk factors, clinical outcome and prognosis following the colonization of CRE in patients that underwent allo-HSCT. Patients and Methods: A total of 343 patients subjected to allo-HSCT in the period comprised between June 2021 and June 2022 were enrolled in this retrospective study. The CRE colonization was diagnosed by clinical history and routine microbial culture of perirectal swab. In this regard, a clinical prediction model was designed based on independent risk factors underlying the pre-transplantation CRE colonization using a backward stepwise logistic regression, followed by the evaluation of its discrimination and calibration efficacies, along with clinical usefulness. Furthermore, univariate and multivariate Cox regression analyses were then conducted to assess the risk factors for post-transplantation clinical outcomes. Results: Out of 343 patients enrolled in this study, 135 (39.3%) reported CRE colonization. The independent risk factor variables for CRE colonization were incorporated into the nomogram to build a prediction model, which showed an area under the curve of 0.767 (95% CI: 0.716-0.818), and well-fitted calibration curves (χ2 = 1.737, P = 0.9788). The patients with CRE colonization reported a significantly lower platelet engraftment rate with a higher risk of post-transplantation BSI when compared with the non-CRE colonization group (P = 0.02 and P < 0.001; respectively). The non-relapse mortality (NRM) value was higher in the CRE patients (P < 0.05), consistently with a survival probability that was thus significantly lower for the same timeframe (P < 0.05). Conclusion: A reliable clinical prediction model for pre-transplantation CRE colonization was developed that demonstrated that the CRE colonization negatively affects platelet engraftment and survival outcomes following allo-HSCT.

Characteristics analysis of epidemiological and antimicrobial resistance of 589 meliodosis bloodstream infection cases in Hainan / 中国热带医学

@#Objective　To provide data support for the prevention and control of melioidosis by analyzing epidemiological characteristics of melioidosis bloodstream infection and antibiotic resistance of its pathogen in Hainan Province from 2012 to 2021. Methods Data was collected from Hainan Antimicrobial Resistance Surveillance System, and WHONET 5.6 software was used to merge and analyze data. Results The case numbers of melioidosis bloodstream infection showed an increasing trend year by year from 2012 to 2021. The ratio of male to female patients was 4.6∶1, with 347 cases (58.91%) of patients aged 40-<60, the age group with the highest incidence. The number of cases from July to November were 424 cases (72.0%). Haikou and Sanya reported the largest case number, with 261 and 116 cases respectively. But there were no case reported from central area including Chengmai, Tunchang, Qiongzhong and Baoting. Burkholderia pseudomallei strains were isolated from both blood and other specimens in 105 of the 589 patients, with respiratory tract and wood specimens being the sites with the highest number of strains isolated other than blood; the resistance rates of Burkholderia pseudomallei to five antibiotics showed no obvious trend of change, with the lowest resistance rate to imipenem among the five drugs at 0.6%, followed by ceftazidime at 2.2%. Conclusion During the typhoon season, elderly, middle-aged male in coastal areas should pay attention to avoid or reduce their contact with mud and water. For patients with melioidosis bloodstream infection, imipenem or ceftazidime should be selected as early as possible for initial treatment.

Changes in key aroma-active compounds and sensory characteristics of sunflower oils induced by seed roasting.

This study investigated the changes in aroma composition and perception of sunflower oils induced by seed roasting using sensory-oriented flavor analysis. Volatile compounds were extracted by solvent-assisted flavor evaporation and headspace solid-phase microextraction. Odorants were characterized by gas chromatography-olfactometry-mass spectrometry and aroma extract dilution analysis. The cold-pressed and roasted sunflower oils contained 13 and 50 odorants, respectively, with the flavor dilution factors between 1 and 256. Fifty-six odorants were newly identified in sunflower oils. Quantification of 26 important odorants by the external standard method revealed apparent changes induced by seed roasting in loss of terpenes, formation of Maillard reaction products, and the increase in lipid oxidation products. The most important odorants (odor active values, OAVs = 1-1857) in the cold-pressed sunflower oil included α-pinene (11,145 µg/kg), ß-pinene (4068 µg/kg), linalool (56 µg/kg), hexanal (541 µg/kg), octanal (125 µg/kg), α-phellandrene (36 µg/kg), and (E)-2-octenal (69 µg/kg), contributing to the raw sunflower seed, woody, green, earthy, and sweet aromas of the oil. The most important contributors (OAVs = 1-884) to the roasted, smoky, and burnt aromas of the roasted sunflower oil were 2- and 3-methylbutanal (6726 and 714 µg/kg), 2,6-dimethylpyrazine (2329 µg/kg), 2,5-dimethylpyrazine (12,228 µg/kg), 2,3-dimethylpyrazine (238 µg/kg), 2,3-pentanedione (1456 µg/kg), 2-pentylfuran (1332 µg/kg), 2,3-dimethyl-5-ethylpyrazine (213 µg/kg), and 1-pentanol (693 µg/kg). Aroma recombination of the key odorants in odorless sunflower oil adequately mimicked the general aroma profiles of sunflower oils. This study provides an important foundation for understanding the relationship between oil processing and aroma molecules of sunflower oils. PRACTICAL APPLICATION: The clear changes observed in the composition and concentrations of key aroma compounds explained the changes in sensory characteristics of sunflower seed oils induced by seed roasting on a molecular basis. Characterizing the key aroma-active composition of sunflower oil and investigating its relationship with oil processing could provide important practical applications for the sunflower oil industry in flavor regulation, quality control, product development, and process optimization.

Comparison of key aroma-active compounds between roasted and cold-pressed sesame oils.

This was the first study to compare the key aroma-active compounds that contributed to the different aroma profiles between roasted and cold-pressed sesame oils. Aroma compounds were extracted by headspace solid-phase micro-extraction (HS-SPME) and simultaneous distillation extraction (SDE) and were analysed using gas chromatography-olfactometry-mass spectrometry (GC-O-MS) and aroma extract dilution analysis (AEDA). The numbers of aroma-active compounds with the flavour dilution (FD) factors between 1 and 2048 were 57 and 16 in the roasted and cold-pressed sesame oils, respectively. A total of 28 volatile compounds were identified as aroma-active compounds in sesame oils for the first time. Important aroma compounds (FD ≥ 8) were quantified by the external standard method, and their odour activity values (OAV) were calculated as the ratio of their concentrations to odour thresholds in oil. The numbers of key aroma-active compounds defined by OAVs ≥ 1 were 23 (OAVs = 1-385) and 8 (OAVs = 1-42), respectively, in the roasted and cold-pressed sesame oils. 2-Methoxy-4-vinylphenol (smoked, 1924 µg/kg, OAV = 385), 2-methoxyphenol (smoked, 1488 µg/kg, OAV = 114) and pyrazines (roasted and nutty, 578-22750 µg/kg, OAV = 1-67) were the most important aroma-active compounds in the roasted sesame oil, whereas hexanal (green and fruity, 3094 µg/kg, OAV = 42) was the most important aroma-active compound in the cold-pressed sesame oil, followed by (E,E)-2,4-decadienal (earthy, 4170 µg/kg, OAV = 31), dimethyl sulfone (sulphur-like, 406 µg/kg, OAV = 20) and octanal (green and fruity, 901 µg/kg, OAV = 16). This study provides valuable information for manufacturers to achieve precise flavour control of sesame oil products.

An integrated machine learning framework for a discriminative analysis of schizophrenia using multi-biological data.

Finding effective and objective biomarkers to inform the diagnosis of schizophrenia is of great importance yet remains challenging. Relatively little work has been conducted on multi-biological data for the diagnosis of schizophrenia. In this cross-sectional study, we extracted multiple features from three types of biological data, including gut microbiota data, blood data, and electroencephalogram data. Then, an integrated framework of machine learning consisting of five classifiers, three feature selection algorithms, and four cross validation methods was used to discriminate patients with schizophrenia from healthy controls. Our results show that the support vector machine classifier without feature selection using the input features of multi-biological data achieved the best performance, with an accuracy of 91.7% and an AUC of 96.5% (p < 0.05). These results indicate that multi-biological data showed better discriminative capacity for patients with schizophrenia than single biological data. The top 5% discriminative features selected from the optimal model include the gut microbiota features (Lactobacillus, Haemophilus, and Prevotella), the blood features (superoxide dismutase level, monocyte-lymphocyte ratio, and neutrophil count), and the electroencephalogram features (nodal local efficiency, nodal efficiency, and nodal shortest path length in the temporal and frontal-parietal brain areas). The proposed integrated framework may be helpful for understanding the pathophysiology of schizophrenia and developing biomarkers for schizophrenia using multi-biological data.

[Resveratrol protects human sperm against cryopreservation-induced injury].

OBJECTIVE: To investigate the effects of resveratrol in the cryopreservation medium on the quality and function of post-thaw sperm. METHODS: Semen samples were obtained from 50 normozoospermic and 50 oligoasthenozoospermic men, liquefied and then cryopreserved in the glycerol-egg yolk-citrate (GEYC) medium with or without 30 µmol/L resveratrol. Sperm motility, viability and acrosome reaction (AR) were examined before and after thawing. Sperm lipid peroxidation and the level of reactive oxygen species (ROS) were measured using commercial malondialdehyde (MDA) and the ROS assay kit. Sperm mitochondrial membrane potential (MMP) and DNA damage were determined by Rhodamine 123 staining and TUNEL. RESULTS: The percentage of progressively motile sperm (PMS), total sperm motility, sperm viability, MMP and AR were significantly decreased (P <0.05) while the levels of sperm ROS, MDA and DNA fragmentation index (DFI) remarkably increased in both the normozoospermia and oligoasthenozoospermia groups after cryopreservation as compared with those in the fresh ejaculate (P <0.05). In comparison with the non-resveratrol control, the post-thaw sperm cryopreserved with 30 µmol/L resveratrol showed markedly higher PMS (ï¼»32.7 ± 4.8ï¼½ vs ï¼»43.1 ± 6.3ï¼½ %, P <0.05), total motility (ï¼»44.8 ± 6.9ï¼½ vs ï¼»56.9 ± 7.4ï¼½ %, P <0.05), viability (ï¼»52.3 ± 6.1ï¼½ vs ï¼»67.5 ± 5.6ï¼½ %, P <0.05), MMP (ï¼»56.5 ± 7.0ï¼½ vs ï¼»63.4 ± 7.5ï¼½ %, P <0.05) and AR (ï¼»16.6 ± 3.8ï¼½ vs ï¼»26.3 ± 4.7ï¼½ %, P <0.05) but lower ROS, MDA and DFI (all P <0.05) in the normozoospermia group, and so did the post-thaw sperm in the oligoasthenozoospermia group, with a particularly lower DFI (ï¼»28.5 ± 4.8ï¼½ vs ï¼»36.3 ± 5.7ï¼½%, P <0.01). CONCLUSIONS: Resveratrol in the cryopreservation medium can improve the quality and function of post-thaw human sperm by reducing cryopreservation-induced sperm injury and the level of ROS.

Expression and function of HSP110 family in mouse testis after vasectomy.

HSP110 functions to protect cells, tissues, and organs from noxious conditions. Vasectomy induces apoptosis in the testis; however, little is known about the reason leading to this outcome. The aim of the present study was to evaluate the expression and function of HSP110 in mouse testis after vasectomy. Following bilateral vasectomy, we used fluorescent Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) to detect apoptosis, Western blotting and immunohistochemistry to examine HSP110 expression and localization. Serum antisperm antibody (AsAb) and testosterone were measured by Enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay, respectively. Expression of endoplasmic reticulum stress (ERS) sensors and downstream signaling components was measured by Reverse Transcription-Polymerase Chain Reaction (RT-PCR), and the phosphorylation of eIF2α and JNK was detected by Western blotting. Vasectomy induced morphologic changes, increased apoptosis in the testis, increased serum AsAb, and decreased testosterone levels. After vasectomy, ORP150 mRNA level was increased first and then decreased, Bcl-2 was decreased, and the expression of HSPA4l, GRP78, GADD153, PERK, ATF6, IRE-1, XBP-1s, Bax, Bak, and caspases and the phosphorylation of eIF2α and JNK were increased. We present that an ER stress-mediated pathway is activated and involved in apoptosis in the testis after vasectomy. HSPA4l and ORP150 may play important roles in maintaining the normal structure and function of testis.

Characterisation of Lyzls in mice and antibacterial properties of human LYZL6.

C-type lysozyme genes (Lyzls) belong to the class of lysozymes and are highly expressed in the testis and epididymis. The members Lyzl4 and Spaca3 have been reported to play a role in sperm-egg binding and fertilisation in mice. However, the function of the remaining two mouse c-type lysozyme genes, Lyzl1 and Lyzl6, is still not clear. In the present study, we analysed the tissue expression and androgen-dependent expression of mouse c-type lysozyme genes and the possible contribution of human recombinant LYZL6 (rLYZL6) to immunity. The expression of Lyzls was detected by RT-PCR, Western blots, immunohistochemistry and immunofluorescence. The bacteriolytic activity of rLYZL6 was analysed by a colony-forming assay. In mice, the expression of Lyzl genes was mainly in the testis and epididymis in a developmentally regulated manner and androgen- or testicular factor-regulated manner. Immunodetection revealed the presence of LYZL6 protein in primary spermatocytes and round spermatids of the testis and on the post-acrosomal area and midpiece of mature epididymal spermatozoa. The rLYZL6 protein exhibited antibacterial activity. From the results, Lyzls may play a role in mitochondrial function of spermatozoa and LYZL6 may contribute to the innate immunity of the male genital tract.

Topical administration of peroxiredoxin-6 on the cornea suppresses inflammation and neovascularization induced by ultraviolet radiation.

PURPOSE: To investigate the effect of topical administration of peroxiredoxin-6 (PRDX6) on ultraviolet-induced corneal injury. METHODS: Corneal transparency and neovascularization were observed with a slit-lamp microscope and hematoxylin and eosin staining. The oxidative damage was determined with a commercial malondialdehyde (MDA) kit. The expressions of PRDX6, polymorphonuclear neutrophil (PMN), vascular endothelial growth factor (VEGF), and pigment epithelium-derived factor (PEDF) were determined by immunohistochemistry and Western blot. The expressions of genes related with antioxidant defense systems and cell apoptosis were detected by RT-PCR. RESULTS: The irradiated corneas appeared opaque and had high levels of MDA. Peripheral neovascularization and neutrophils appeared in the control and buffer-treated groups (with no treatment or PRDX6 diluent, respectively), whereas they were significantly suppressed in the PRDX6-treated group. The MDA content of the corneas in the PRDX6-treated group was significantly lower than that of the control and buffer-treated groups (P < 0.05). In the PRDX6-treated group the immunoreactivity of VEGF was lower, and that of PEDF was higher, than that in the control and buffer-treated groups. In addition, there were expression correlations between PRDX6 and PMN, VEGF, PEDF. The expressions of genes related with antioxidant defense systems and cell apoptosis were significant different between buffer- and PRDX6-treated groups (P < 0.05). CONCLUSIONS: The topically administered PRDX6 maintained the homeostasis of corneal cells, reduced inflammation, and suppressed neovascularization and apoptosis under ultraviolet irradiation.

[Forebrain NMDA receptor 2B subunit over-expression has no influence on anxiety behaviors of mice.].

It has been known that the glutamate transmission system and N-methyl-D-aspartate receptor (NMDA-R) were possibly related to anxiety processes. Although anxiety symptom can be relieved by NMDA-R antagonists and partial agonists treatment, the functions of NMDA-R and its subunits in anxiety behaviors remain unclear. We used forebrain specific NR2B over-expression mice to examine whether the increase of NR2B subunit level would induce anxiety behaviors. The results indicated that the juvenile (3-5 months old), middle-aged (8-10 months old) and old (19-22 months old ) NR2B transgenic mice showed no significant difference in open field test and elevated plus maze test as compared with the control mice. Capillary electrophoresis of monoamine neurotransmitter in subregions of forebrain revealed no significant difference between transgenic and control mice of 16-18 months age. These results suggest that the increase of NR2B expression and followed NR1 and NR2A expression augmentations in the forebrain have no significant effect on anxiety-related behaviors in mice.