Development and advancements in rodent MRI-based brain atlases.

Rodents, particularly mice and rats, are extensively utilized in fundamental neuroscience research. Brain atlases have played a pivotal role in this field, evolving from traditional printed histology atlases to digital atlases incorporating diverse imaging datasets. Magnetic resonance imaging (MRI)-based brain atlases, also known as brain maps, have been employed in specific studies. However, the existence of numerous versions of MRI-based brain atlases has impeded their standardized application and widespread use, despite the consensus within the academic community regarding their significance in mice and rats. Furthermore, there is a dearth of comprehensive and systematic reviews on MRI-based brain atlases for rodents. This review aims to bridge this gap by providing a comprehensive overview of the advancements in MRI-based brain atlases for rodents, with a specific focus on mice and rats. It seeks to explore the advantages and disadvantages of histologically printed brain atlases in comparison to MRI brain atlases, delineate the standardized methods for creating MRI brain atlases, and summarize their primary applications in neuroscience research. Additionally, this review aims to assist researchers in selecting appropriate versions of MRI brain atlases for their studies or refining existing MRI brain atlas resources, thereby facilitating the development and widespread adoption of standardized MRI-based brain atlases in rodents.

Polysaccharide-Based Coating with Excellent Antibiofilm and Repeatable Antifouling-Bactericidal Properties for Treating Infected Hernia.

In recent years, the utilization of medical devices has gradually increased and implantation procedures have become common treatments. However, patients are susceptible to the risk of implant infections. This study utilized chemical grafting to immobilize polyethylenimine (QPEI) and hyaluronic acid (HA) on the surface of the mesh to improve biocompatibility while being able to achieve antifouling antimicrobial effects. From the in vitro testing, PP-PDA-Q-HA exhibited a high antibacterial ratio of 93% against S. aureus, 93% against E. coli, and 85% against C. albicans. In addition, after five rounds of antimicrobial testing, the coating continued to exhibit excellent antimicrobial properties; PP-PDA-Q-HA also inhibits the formation of bacterial biofilms. In addition, PP-PDA-Q-HA has good hemocompatibility and cytocompatibility. In vivo studies in animal implantation infection models also demonstrated the excellent antimicrobial properties of PP-PDA-Q-HA. Our study provides a promising strategy for the development of antimicrobial surface medical materials with excellent biocompatibility.

Effectiveness of conjunctival bleb scarring by knock-down of heat shock protein 47 in rat model.

AIM: To evaluate the effectiveness of knock-down of heat shock protein 47 (HSP47) on conjunctival bleb scarring in a rat model and its possible mechanism. METHODS: Male Sprague-Dawley rats were used for glaucoma filtration surgery (GFS) and were treated with either phosphate buffered solution, shControl, mitomycin C, or sh-HSP47 using a microsyringe immediately after GFS. The morphology of filtering blebs was observed postoperatively. The levels of HSP47 were analyzed at 2, 5, 8, and 11d after GFS via real-time quantitative polymerase chain reaction (PCR) and Western blot. The silencing effect of HSP47, the expression of collagen I and III, and the potential signaling pathways of HSP47 during scarification were explored 11d post GFS. The protein levels of transforming growth factor-ß1 (TGF-ß1), phospho-Smad2 (pSmad2), phospho-Smad3 (p-Smad3), and phospho-p38 (p-p38) were also analyzed using Western blot. RESULTS: Sh-HSP47 treatment significantly prolonged the functional filtration bleb retention. The levels of HSP47 were increased significantly at 5, 8, and 11d postoperatively compared to the control group (P<0.05, P<0.01, and P<0.001). The levels of HSP47 protein at day 11 postoperatively were significantly down-regulated after HSP47 silencing using sh-HSP47 adenovirus transfection (P<0.01). Expression levels of collagen I and III within the blebs were significantly reduced in the absence of HSP47 (P<0.01). Moreover, the protein levels of TGF-ß1, p-Smad2/3, and p-p38 were dramatically inhibited after treatment with sh-HSP47 (P<0.01). CONCLUSION: The inhibitory effects of HSP47 knock-down on scarring after GFS have the potential to be an efficacious therapeutic option for the treatment of conjunctival bleb scarring.

The decreased of peripheral blood natural killer cell is associated with serum IL-2 level in the renal tubular acidosis in patients with primary sjogren's syndrome.

BACKGROUND: Primary Sjogren's Syndrome (pSS) is a lymphoproliferative disease with autoimmune characteristics, which is characterized by lymphocyte infiltration of exocrine glands and involvement and dysfunction of extraglandular organs. Renal tubular acidosis (RTA) is a common renal involvement in pSS. This study investigated the phenotypic characteristics of peripheral blood lymphocyte subsets and cytokines in pSS patients complicated with RTA (pSS-RTA). METHOD: This retrospective study included 25 pSS patients complicated with RTA and 54 pSS patients without RTA (pSS-no-RTA). To examine the level of peripheral lymphocytes subsets, flow cytometry analysis was used. The level of serum cytokines were detected by flow cytometry bead array(CBA). The influencing factors related to the occurrence of pSS-RTA were identified through logistic regression analyze. RESULTS: The absolute number of CD4 + T cells and Th2 cells in peripheral blood were decreased in pSS-RTA patients than pSS-no-RTA patients. Moreover, the absolute number of NK cells and Treg cells were also decreased in pSS-RTA patients than pSS-no-RTA. The level of serum IL-2 was higher in pSS-RTA patients than pSS-no-RTA patients, and is negatively correlated with the number of NK cells, the number and percentage of Th17 cells, and Th17/Treg. Serum IL-2 level is also correlated with various cytokines. Multivariate logistic analysis proved that elevated ESR and ALP were risk factors for pSS complicated with RTA, while Treg was a protective factor. CONCLUSION: The increase of serum IL-2 level and the decrease of peripheral blood NK cells and Treg cells may be the immune mechanism of the development of pSS-RTA disease.

Multifunctional xyloglucan-containing electrospun nanofibrous dressings for accelerating infected wound healing.

Preventing wound infection is a major challenge in biomedicine. Conventional wound dressings often have poor moisturizing and antimicrobial properties unfavorable for wound healing. In this study, we prepared a multifunctional electrospun nanofiber dressing (PCQX-M) containing xyloglucan, quaternized chitosan, Polyvinyl alcohol, and collagen. By applying the concept of wet healing, xyloglucan and quaternized chitosan polysaccharides with excellent water solubility were employed to improve the absorption and moisturizing properties and maintain a moist microenvironment for the wound healing process. PCQX-M demonstrated high mechanical, thermodynamic, and biocompatible properties, providing suitable healing conditions for wounds. In addition, PCQX-M showed exceptional antibacterial properties and a potential inhibitory effect on the growth of microorganisms in infected wounds. More intriguingly, the restorative healing effect was investigated on a mouse model of whole skin injury infected with Staphylococcus aureus. Wound healing, collagen deposition, and immunofluorescence results showed that PCQX-M significantly promoted cell proliferation and angiogenesis at the injury site and facilitated the healing of the infected wound. Our study suggests that PCQX-M has excellent potential for clinical application in infected wound healing.

Validation of a Disease-Free Survival Prediction Model Using UBE2C and Clinical Indicators in Breast Cancer Patients.

Objective: To explore the validation of a disease-free survival (DFS) model for predicting disease progression based on the combination of ubiquitin-conjugating enzyme E2 C (UBE2C) levels and clinical indicators in breast cancer patients. Methods: We enrolled 121 patients with breast cancer, collected their baseline characteristics and follow-up data, and analyzed the UBE2C levels in tumor tissues. We studied the relationship between UBE2C expression in tumor tissues and disease progression events of patients. We used the Kaplan-Meier method for identifying the disease-free survival rate of patients, and the multivariate Cox regression analysis to study the risk factors affecting the prognosis of patients. We sought to develop and validate a model for predicting disease progression. Results: We found that the level of expression of UBE2C could effectively distinguish the prognosis of patients. In the Receiver Operating Characteristic (ROC) curve analysis, the Area under the ROC Curve (AUC) = 0.826 (0.714-0.938) indicating that high levels of UBE2C was a high-risk factor for poor prognosis. After evaluating different models using the ROC curve, Concordance index (C-index), calibration curve, Net Reclassification Index (NRI), Integrated Discrimination Improvement Index (IDI), and other methods, we finally developed a model for the expression of Tumor-Node (TN) staging using Ki-67 and UBE2C, which had an AUC=0.870, 95% CI of 0.786-0.953. The traditional TN model had an AUC=0.717, and 95% CI of 0.581-0.853. Decision Curve Analysis (DCA) and Clinical Impact Curve (CIC) analysis indicated that the model had good clinical benefits and it was relatively simple to use. Conclusion: We found that high levels of UBE2C was a high-risk factor for poor prognosis. The use of UBE2C in addition to other breast cancer-related indicators effectively predicted the possible disease progression, thus providing a reliable basis for clinical decision-making.

Network meta-analysis of intravitreal conbercept as an adjuvant to vitrectomy for proliferative diabetic retinopathy.

Purpose: Intravitreal Conbercept (IVC) has been shown to be effective in treating proliferative diabetic retinopathy (PDR) as an adjuvant in pars plana vitrectomy (PPV); however, the best timing of IVC injection remains unknown. This network meta-analysis (NMA) sought to ascertain the comparative efficacy of different timings of IVC injection as an adjuvant to PPV on PDR. Methods: A comprehensive literature search was conducted in PubMed, EMBASE, and the Cochrane Library to identify relevant studies published before August 11, 2022. According to the mean time of IVC injection before PPV, the strategy was defined as very long interval if it was > 7 days but ≤ 9 days, long interval if it was > 5 days but ≤ 7 days, mid interval if it was > 3 days but ≤ 5 days, and short interval if it was ≤ 3 days, respectively. The strategy was defined as perioperative IVC if IVC was injected both before and at the end of PPV, and the strategy was intraoperative IVC if injected immediately at the end of PPV. The mean difference (MD) and odds ratio (OR) with corresponding 95% confidence interval (CI) for continuous and binary variables, respectively, were computed through network meta-analysis using Stata 14.0 MP. Results: Eighteen studies involving 1149 patients were included. There was no statistical difference between intraoperative IVC and control in treating PDR. Except for a very long interval, preoperative IVC significantly shortened operation time, and reduced intraoperative bleeding and iatrogenic retinal breaks. Long and short intervals reduced endodiathermy application, and mid and short intervals reduced postoperative vitreous hemorrhage. Moreover, long and mid intervals improved BCVA and central macular thickness. However, very long interval was associated with an increased risk of postoperative vitreous hemorrhage (RR: 3.27, 95%CI: 1.84 to 5.83). Moreover, mid interval was better than intraoperative IVC in shortening operation time (MD: -19.74, 95%CI: -33.31 to -6.17). Conclusions: There are no discernible effects of intraoperative IVC on PDR, but preoperative IVC, except for very long interval, is an effective adjuvant to PPV for treating PDR.

Conductive Polyaniline Particles Regulating In Vitro Hydrolytic Degradation and Erosion of Hydroxyapatite/Poly(lactide-co-glycolide) Porous Scaffolds for Bone Tissue Engineering.

In addition to biocompatibility and bioactivity, scaffolds with superior bone tissue regenerative capacity should possess excellent functionality (e.g., electroactivity and conductivity) and biodegradability matching with the rate of bone reconstruction. However, current conductive scaffolds display a reduced biodegradability rate and weakened biocompatibility. In this study, injectable conductive porous scaffolds were fabricated, incorporating camphor sulfonic acid-doped polyaniline (PANI) into hydroxyapatite/poly(lactide-co-glycolide) (HA/PLGA) scaffolds, using solvent-casting/particulate-leaching methodology. These scaffolds demonstrated excellent electroactivity, conductivity, hydrophilicity, thermodynamic properties, antibacterial properties, and biocompatibility. Their degradation behavior was explored by regulating the PANI content. The results demonstrated that adding an appropriate content of PANI would increase the pore size, porosity, and water absorption of the conductive scaffold and promote the formation of filamentous fiber byproducts with acidic hydrolysates, which accelerated the degradation rate of the scaffold. Owing to π-π stacking and hydrogen bonding, the conductive scaffold with 10 wt % PANI efficiently retarded the decrease in the thermal and mechanical properties of the scaffolds during a 16 week degradation. Thus, better regulation of degradation behavior and correlation would allow conductive porous scaffolds, such as bone implants, to achieve better bone ingrowth and restoration.

The expression pattern, subcellular localization and function of three sterol 14α-demethylases in Aspergillus oryzae.

Sterol 14α-demethylase catalyzes lanosterol hydroxylation, which is one of the key reactions in the biosynthetic pathway of sterols. There is only one sterol 14α-demethylases gene named Erg11 in Saccharomyces cerevisiae genome. In this study, three sterol 14α-demethylases genes named AoErg11A, AoErg11B and AoErg11C were identified in Aspergillus oryzae genome through bioinformatics analysis. The function of these three genes were studied by yeast complementation, and the expression pattern/subcellular localization of these genes/proteins were detected. The results showed that the three AoErg11s were expressed differently at different growth times and under different abiotic stresses. All of the three proteins were located in endoplasmic reticulum. The AoErg11s could not restore the temperature-sensitive phenotype of S. cerevisiae erg11 mutant. Overexpression of the three AoErg11s affected both growth and sporulation, which may be due to the effect of AoErg11s on ergosterol content. Therefore, this study revealed the functions of three AoErg11s and their effects on the growth and ergosterol biosynthesis of A. oryzae, which may contribute to the further understanding of the ergosterol biosynthesis and regulation mechanism in this important filamentous fungus, A. oryzae.

Gamma-Aminobutyric Acid Promotes Beige Adipocyte Reconstruction by Modulating the Gut Microbiota in Obese Mice.

Given the increasing prevalence of obesity, the white-to-beige adipocyte conversion has attracted interest as a target for obesity treatment. Gamma-aminobutyric acid (GABA) treatment can reduce obesity, but the underlying mechanism remains unclear. Here, we aimed to investigate the mechanism by which GABA triggers weight loss by improving the beiging of inguinal white adipose tissue (iWAT) and the role of gut microbiota in this process. The results showed that GABA reduced body weight and adipose inflammation and promoted the expression of thermogenic genes in the iWAT. The 16S rRNA sequence analysis of gut microbiota showed that GABA treatment increased the relative abundance of Bacteroidetes, Akkermansia, and Romboutsia and reduced that of Firmicutes and Erysipelatoclostridium in obese mice. Additionally, serum metabolomic analysis revealed that GABA treatment increased 3-hydroxybutyrate and reduced oxidized lipid levels in obese mice. Spearman's correlation analysis showed that Akkermansia and Romboutsia were negatively associated with the levels of oxidized lipids. Fecal microbiota transplantation analysis confirmed that the gut microbiota was involved in the white-to-beige adipocyte reconstruction by GABA. Overall, our findings suggest that GABA treatment may promote iWAT beiging through the gut microbiota in obese mice. GABA may be utilized to protect obese people against metabolic abnormalities brought on by obesity and gut dysbiosis.

Low-dose interleukin-2 treatment increases the proportion of regulatory T cells in patients with rheumatic diseases: A meta-analysis.

BACKGROUND: It is now accepted that immune tolerance disorders caused by inadequate Treg cell function or number are important factors in the development and progression of rheumatic diseases. There is increasing evidence that ld IL-2 treatment increases the proportion of Treg cells in patients' peripheral blood, but this conclusion is still controversial. Here, we performed a meta-analysis of reports documenting the proportion of Treg cells and the rate of adverse events in patients with rheumatic disease before and after the administration of ld IL-2 to better understand its effect and safety on Treg cells in the field of rheumatic diseases. METHODS: We systematically searched PubMed, Embase, Scopus, Cochrane Library, and Web of science databases up to 15th November 2022 and identified studies that reported the proportion of peripheral blood Treg cells before and after ld IL-2 treatment in patients with rheumatic disease. Random-effects model was used to perform a meta-analysis of Treg cell proportions before and after ld IL-2 administration, and a meta-regression analysis was performed to explore heterogeneity. Inconsistency was evaluated using the I-squared index (I2), and publication bias was assessed by examining funnel plot asymmetry using the Egger tests. RESULTS: Eighteen studies involving 1608 patients were included in the meta-analysis. The proportion of Treg cells in peripheral blood of these patients increased significantly after receiving ld IL-2 treatment [1.07 (95% CI 0.86,1.27), p < 0.001, I2 = 67.3%]. Next, Meta-regression was performed for 5 variables including publish year, disease type, trail type and dosage and duration of the medication. The results suggest that these variables do not lead to high heterogeneity. (p = 0.698, 0.267, 0.502, 0.843, 0.560, respectively). And finally, statistical analysis showed no difference in adverse reactions between ld IL-2 group and control group in treatment [1.06 (95% CI 0.86,1.31), p = 0.586, I2 = 53.8%], which is unreliable because the data is so small. CONCLUSIONS: Ld IL-2 does increase the proportion of peripheral blood Treg cells in patients with rheumatism, and single and cumulative doses must be considered when using ld IL-2. In addition, more studies on the safety of ld IL-2 are urgently needed.

Establishment and Validation of a Model for Disease-Free Survival Rate Prediction Using the Combination of microRNA-381 and Clinical Indicators in Patients with Breast Cancer.

Objective: We have found that miR-381 can regulate the proliferation of breast cancer cells by regulating TWIST protein, it can serve as a potential marker for the tumor progression. Thus, we herein establishment and validation of a model for predicting disease progression in patients with breast cancer using a combination of microRNA-381 (miR-381) and clinical indicators. Methods: Data from 160 breast cancer patients in the First People's Hospital of Lianyungang were collected, The relationship between miR-381 expression and tumor subtype was analyzed. The Kaplan-Meier (K-M) curve method was used to investigate the disease-free survival rate, while multivariate Cox regression analysis was used to investigate the risk factors affecting the prognosis of the patients. A model for predicting disease progression was subsequently established and validated. Results: The miR-381 was significantly higher in the stage I patients than stage II/III patients. The miR-381 level of triple-negative breast cancer (TNBC) type was significantly decreased. The miR-381 could be used to effectively predict the prognosis, using cut-off value of 0.2515, with a sensitivity of 65.38% (51.8-76.85%), specificity of 75.00% (46.77-91.11%). The K-M survival curve indicated that the patients with higher miR-381 expression had a better prognosis. The miR-381+Ki-67+TN model and TN (T and N in TNM staging) model were established and subsequently compared. The TN model had an area under the curve (AUC) of 0.479 (95% CI 0.329, 0.629); in comparison, the our model had an AUC of 0.719 (95% CI 0.580, 0.857), showing better performance. Conclusion: The miR-381 expression was correlated with different (TNM) stages and tumor subtypes. The higher the TNM stage, the lower the miR-381 expression in the tumor tissue, while it was significantly decreased in TNBC. A prediction model consisting of combination of miR-381 and Ki-67 and TN indicators could predict disease progression more effectively.

Decreased absolute number of peripheral regulatory T cells in patients with idiopathic retroperitoneal fibrosis.

Objective: In order to determine whether the immune balance of T helper 17(Th17)/regulatory T(Treg) is related to the pathogenesis of idiopathic retroperitoneal fibrosis (IRPF), we analyzed the differences in peripheral blood lymphocytes, CD4+T cell subsets and cytokines between patients with IRPF and healthy people to clarify the CD4+T cell subsets, especially Treg cell subsets, and the role of cytokines in the pathogenesis of IRPF. Methods: This study included 22 patients with IRPF, 36 patients with IgG4-related diseases (IgG4-RD) without retroperitoneal fibrosis (RPF), and 28 healthy controls. The absolute numbers and percentage of peripheral blood lymphocyte subsets and CD4+T cell subsets in each group were detected by flow cytometry, and the serum cytokine level was detected by flow cytometric bead array (CBA). Results: Compared with the healthy group, the absolute value of B cells in peripheral blood of IRPF patients was significantly decreased, and T, natural killer (NK), CD4+ and CD8+ were not significantly abnormal. The absolute numbers of Th2 cells were lower than healthy group(p=0.043). In particular, the absolute numbers of Treg cells were significantly lower than healthy group(p<0.001), while the absolute numbers of Th17 cells increased(p=0.682). Th17/Treg was significantly higher than healthy group (p< 0.001). Cytokine analysis showed that the level of interleukin (IL)-4 in IRPF patients was higher than healthy group(p=0.011), IL-6, IL-10, IL-17, TNF-α and IFN-γ were significantly higher than healthy group (all p<0.001). Receiver operating characteristic (ROC) curves showed that IL-10 and TNF-α could distinguish bilateral ureteral dilatation in IRPF patients, with areas under the ROC curve (AUCs) of 0.813 (95% CI:0.607-1.000, p=0.026) and 0.950 (95% CI:0.856-1.000, p=0.001), respectively. IL-6 could distinguish bilateral ureteral obstruction, with an AUC of 0.861 (95% CI: 0.682-1.000, p=0.015). Conclusions: Our study showed that IRPF patients had reduced Treg cells and indeed had Th17/Treg imbalance, which may be related to the pathogenesis of the disease. The levels of IL-6, IL-10 and TNF-α appear to be associated with the progression of IRPF.

High Levels of Heat Shock Protein 47 in the Aqueous Humor of Patients with Acute Primary Angle Closure.

INTRODUCTION: Acute primary angle closure (APAC) is often characterized by acute elevation of intraocular pressure (IOP) accompanied by severe ocular and systemic symptoms. Excessive collagen accumulation, which can be caused by upregulated heat shock protein 47 (HSP47) expression, can produce scarring in rat conjunctival blebs. Meanwhile, the presence of HSP47 in human aqueous humor and its levels are yet to be determined. METHODS: We examined 32 consecutive patients with APAC and 16 age-matched participants without APAC scheduled for cataract surgery who were enrolled as a control group. Aqueous humor samples were collected from all subjects at the time of surgery and compared between the subjects with and without APAC. RESULTS: The levels of HSP47 in the aqueous humor of patients with APAC (1,210.4 ± 450.2 pg/mL) were found to be significantly increased (P = 0.001) compared with those in the control group (863.4 ± 240.0 pg/mL). Notably, the levels of HSP47 negatively correlated with the age of patients with APAC (P = 0.023). CONCLUSION: HSP47 was upregulated in the aqueous humor of patients with APAC and may play a role in scarring after trabeculectomy for APAC.

Application value of blood metagenomic next-generation sequencing in patients with connective tissue diseases.

Objective: This study aimed to analyze the application value of blood metagenomic next-generation sequencing (mNGS) in patients with connective tissue diseases (CTDs) to provide a reference for infection diagnosis and guidance for treatment. Methods: A total of 126 CTD patients with suspected infections who were hospitalized in the Department of Rheumatology, the Second Hospital of Shanxi Medical University from January 2020 to December 2021 were enrolled in this study. We retrospectively reviewed the results of mNGS and conventional diagnostic tests (CDTs). Results: Systemic lupus erythematosus (SLE) and polymyositis/dermatomyositis (DM/PM) had the highest incidence of infections. The positive pathogen detection rates of mNGS were higher than those of CDT. The virus infections are the most common type in CTD patients with single or mixed infection, especially Human gammaherpesvirus 4 (EBV), Human betaherpesvirus 5 (CMV), and Human alphaherpesvirus 1. The incidence of prokaryote and eukaryote infections is secondary to viruses. Bloodstream infections of rare pathogens such as Pneumocystis jirovecii should be of concern. Meanwhile, the most common mixed infection was bacterial-virus coinfection. Conclusion: mNGS has incremental application value in patients with CTD suspected of co-infection. It has a high sensitivity, and a wide detection range for microorganisms in CTD patients. Furthermore, the high incidence of opportunistic virus infections in CTD patients should be of sufficient concern.

Immunological risk factors for nonalcoholic fatty liver disease in patients with psoriatic arthritis: New predictive nomograms and natural killer cells.

Objective: To search for the immunological risk factors of Psoriatic arthritis (PsA) combined with nonalcoholic fatty liver disease (NAFLD), development and assessment of predictive nomograms for NAFLD risk in patients with PsA, and to further explore the correlation between risk factors and dyslipidemia. Methds: A total of 127 patients with PsA (46 with NAFLD and 81 without NAFLD) were included in this retrospective study. The clinical and serological parameters of the patients were collected. The percentage and the absolute number of lymphocytes and CD4+T cells were determined by Flow cytometry. Univariate and multivariate binary logistic regression analysis was used to screen independent risk factors of PsA complicated with NAFLD in the model population, and a nomogram prediction model was developed and assessed. Results: (1) Univariate and multivariate logistic regression analysis of the modeling population showed that the percentage of peripheral blood T helper 1 cells (Th1%) (OR=1.12, P=0.001), body mass index (BMI) (OR=1.22, P=0.005) and triglycerides (TG) (OR=4.78, P=0.003) were independent risk factors for NAFLD in patients with PsA, which were incorporated and established a nomogram prediction model. The model has good discrimination and calibration, and also has certain clinical application value. (2) The number of peripheral blood NK cells in PsA patients was significantly positively correlated with serum triglyceride (TG) (r=0.489, P<0.001), cholesterol (CHOL) (r=0.314, P=0.003) and low-density lipoprotein (LDL) (r=0.362, P=0.001) levels. Conclusions: Our study shows that the novel NAFLD nomogram could assess the risk of NAFLD in PsA patients with good efficiency. In addition, peripheral blood NK cell levels may be associated with dyslipidemia in patients with PsA.

Preliminary Study on the Imbalance Between Th17 and Regulatory T Cells in Antiphospholipid Syndrome.

Objective: Patients with antiphospholipid syndrome (APS) have immune cell abnormalities that remain poorly understood. This study compared primary APS (PAPS) and secondary APS (SAPS) patients with healthy controls with respect to peripheral blood lymphocytes, CD4+T cell subsets, and cytokine levels. The correlation between antiphospholipid antibody titres and T helper 17 (Th17) and T regulatory (Treg) cell subsets was also analyzed, together with the correlations between cytokine profiles and the clinical characteristics of APS patients. Methods: The retrospective study population consisted of 67 APS patients (12 with PAPS, 55 with SAPS) and 40 healthy controls. Absolute numbers of peripheral blood lymphocyte subsets and CD4+ T cell subsets were detected by flow cytometry, and serum cytokine levels by flow cytometry bead array. Results: Patients with SAPS had lower absolute values of T, B and CD4+T cells than the healthy control group, while only natural killer (NK) cell levels were decreased in patients with PAPS. Absolute numbers of T, B, NK, and CD4+T cells were significantly higher in the PAPS than SAPS group. The trends in CD4+T cell subsets were the same in PAPS and SAPS patients as in healthy controls, with increased Th1, decreased Th2, and decreased Treg levels, and thus an increased Th17/Treg ratio. Th2, Th17, and Treg cell counts were higher in the PAPS than SAPS group. Cytokine analysis showed that only IL-10 levels differed between the two APS groups. However, the levels of all of the studied cytokines were higher in APS patients than healthy controls, and correlated with the clinical characteristics of the patients. In the PAPS group, the titres of two autoantibodies correlated positively with the Th17/Treg ratio and negatively with the levels of D-dimer and Treg subsets. Conclusions: Our study clearly showed that APS patients have immune disturbances, the most prominent of which is an increase in the Th17/Treg ratio, due to a decrease in the number of Treg cells. These abnormalities may be involved in the occurrence and progression of APS. An additional finding was a higher level of peripheral blood lymphocytes in PAPS than SAPS patients, which may be related to the immunosuppressive treatment of SAPS patients.

Comparison of Chinese and American subjects on the self-administered Waterless Empirical Taste Test.

Cultural differences have been reported between the taste sensitivity of persons of Asian and European ancestry, although findings have been mixed. This study sought to determine whether American and Chinese adults perform differently on a novel taste test that requires no water, can be self-administered, and employs a representative of umami as one of its tastants. This 53-trial test was administered to 113 Chinese and 214 Americans. The subjects orally sampled monomer cellulose pads containing one of four dried concentrations of sucrose, citric acid, NaCl, caffeine, and monosodium glutamate and indicated whether a sweet, sour, bitter, salty, brothy, or no taste sensation was perceived. Separate gender by culture analyses of covariance with age as the covariate were performed on the total score and the scores of each taste stimulus. For all taste qualities, women outperformed men and test scores declined with age. No difference between American and Chinese subjects was found for the total taste score (p = .129) or for the sucrose (p = .129) or NaCl (p = .368) scores. However, for monosodium glutamate, the scores were 28.40% higher for the Chinese than for the American subjects (p = .024), and for citric acid and caffeine, the scores were 24.12 and 21.79% higher for the American subjects (p's = .001 and .029). The basis for these differences is unclear, although both anatomical (e.g., differences in density or distribution of taste buds) and cultural factors may be involved. Future work is needed to determine the cause of these largely novel findings and whether they generalize to other Chinese and American samples. Practical applicationsIn this study, a practical self-administered quantitative taste test that requires no water was found to be sensitive to quality-specific differences in test scores between Chinese and American subjects, as well as to age and gender. The Chinese subjects outperformed the American subjects in correctly identifying the quality of monosodium glutamate (umami), whereas the American subjects outperformed Chinese subjects in correctly identifying the bitter and sour qualities of caffeine and citric acid, respectively. Experiential factors related to culture-specific cuisines may explain some of these differences. This research indicates that a relatively rapid taste test, which can be sent through the mail and which requires no test administrator or source of water, can be used in cross-cultural studies to elucidate individual differences in taste perception.

Inhibition of RIPK1 by ZJU-37 promotes oligodendrocyte progenitor proliferation and remyelination via NF-κB pathway.

Receptor interacting serine/threonine protein kinase 1 (RIPK1) activation and necroptosis have been genetically and mechanistically linked with human multiple sclerosis and neurodegenerative diseases for which demyelination is a common key pathology. Demyelination can be healed through remyelination which is mediated by new oligodendrocytes derived from the adult oligodendrocyte progenitor cells (OPCs). Unfortunately, the efficiency of remyelination declines with progressive aging partially due to the depletion of OPCs following chronic or repeated demyelination. However, to our knowledge, so far there is no drug which enhances proliferation of OPCs, and it is unknown whether inhibiting RIPK1 activity directly affect OPCs, the central player of remyelination. Using TNFα induced RIPK1-dependent necroptosis in Jurkat FADD-/- cells as a cell death assay, we screened from 2112 FDA-approved drugs and the drug candidates of new RIPK1 inhibitors selected by ourselves, and identified ZJU-37, a small molecule modified by introducing an amide bond to Nec-1s, is a new RIPK1 kinase inhibitor with higher potency than Nec-1s which has the best reported potency. We unveil in addition to protecting myelin from demyelination and axons from degeneration, ZJU-37 exhibits a new role on promoting proliferation of OPCs and enhancing remyelination by inhibiting RIPK1 kinase activity with higher potency than Nec-1s. Mechanistically, ZJU-37 promotes proliferation of OPCs by enhancing the transcription of platelet derived growth factor receptor alpha via NF-κB pathway. This work identifies ZJU-37 as a new drug candidate which enhances remyelination by promoting proliferation of OPCs, paving the way for a potential drug to enhance myelin repair.

Research Progress on Cordycepin Synthesis and Methods for Enhancement of Cordycepin Production in Cordyceps militaris.

C. militaris is an insect-born fungus that belongs to Ascomycota and Cordyceps. It has a variety of biological activities that can be applied in medicine, health-care products, cosmeceuticals and other fields. Cordycepin (COR) is one of the major bioactive components identified from C. militaris. Thus, C. militaris and COR have attracted extensive attention. In this study, chemical synthetic methods and the biosynthesis pathway of COR were reviewed. As commercially COR was mainly isolated from C. militaris fermentation, the optimizations for liquid and solid fermentation and genetic modifications of C. militaris to increase COR content were also summarized. Moreover, the research progress of genetic modifications of C. militaris and methods for separation and purification COR were introduced. Finally, the existing problems and future research direction of C. militaris were discussed. This study provides a reference for the production of COR in the future.