Relationships between obesity and prevalence of gout in patients with type 2 diabetes mellitus: a cross-sectional population-based study.

BACKGROUND: The purpose of this study was to investigate the relationships between generalized, abdominal, and visceral fat obesity and the prevalence of gout in patients with type 2 diabetes mellitus (T2DM). METHODS: Data were obtained from the electronic medical databases of the National Metabolic Management Center (MMC) of Yuhuan Second People's Hospital and Taizhou Central Hospital (Taizhou University Hospital) between September 2017 and June 2023. Four obesity indicators were analyzed: waist circumference (WC), waist-to-hip ratio (WHR), body mass index (BMI), and visceral fat area (VFA). The relationships between these parameters and gout prevalence were analyzed using multivariate logistic regression and restricted cubic spline (RCS) analyses. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficacy of the four parameters for gout. RESULTS: This cross-sectional study enrolled 10,535 participants (600 cases and 9,935 controls). Obesity was more common in patients with gout, and the obesity indicators were markedly higher in this group. After adjustment for confounders, obesity, as defined by BMI, WC, WHR, and VFA, was found to be associated with greater gout prevalence, with odds ratios (OR) of 1.775, 1.691, 1.858, and 1.578, respectively (P < 0.001). The gout odds ratios increased markedly in relation to the obesity indicator quartiles (P-value for trend < 0.001), and the obesity indicators were positively correlated with gout prevalence, as shown using RCS. The area under the ROC curve values for BMI, WC, WHR, and VFA were 0.629, 0.651, 0.634, and 0.633, respectively. CONCLUSION: Obesity-whether general, abdominal, or visceral fat obesity-was positively linked with elevated gout risk. But uncovering the causality behind the relationship requires further prospective study. Obesity indicators (BMI, WC, WHR, and VFA) may have potential value for diagnosing gout in clinical practice.

Hofmeister Effect-Assisted Facile Fabrication of Self-Assembled Poly(Vinyl Alcohol)/Graphite Composite Sponge-Like Hydrogel for Solar Steam Generation.

The use of hydrogel-based interfacial solar evaporators for desalination is a green, sustainable, and extremely concerned freshwater acquisition strategy. However, developing evaporators that are easy to manufacture, cheap, and have excellent porous structures still remains a considerable challenge. This work proposes a novel strategy for preparing a self-assembling sponge-like poly(vinyl alcohol)/graphite composite hydrogel based on the Hofmeister effect for the first time. The sponge-like hydrogel interfacial solar evaporator (PGCNG) is successfully obtained after combining with graphite. The whole process is environmental-friendly and of low-carbon free of freezing process. The PGCNG can be conventionally dried and stored. PGCNG shows impressive water storage performance and water transmission capacity, excellent steam generation performance and salt resistance. PGCNG has a high evaporation rate of 3.5 kg m-2 h-1 under 1 kW m-2 h-1 solar irradiation and PGCNG demonstrates stable evaporation performance over both 10 h of continuous brine evaporation and 30 cycles of brine evaporation. Its excellent performance and simple, scalable preparation strategy make it a valuable material for practical interface solar seawater desalination devices.

Association between physical activity and the prevalence of gout among patients with type 2 diabetes mellitus and hyperuricemia: a two-center population-based cross-sectional study.

INTRODUCTION: Diabetes mellitus (DM) and gout cohabitation severely reduces patient life quality while raising financial burden on individual and society. The aim of this study was to elucidate the association between physical activity (PA) and the prevalence of gout among type 2 DM (T2DM) and hyperuricemia (HUA) patients. METHODS: In all, we recruited 2291 T2DM patients with HUA. Among them, 448 had gout and 1843 did not. We collected patient data, such as anthropometry, laboratory reports, and medical history, for our analyses. The PA assessment was based on the Chinese version of International PA Questionnaire-short (IPAQ). Moreover, the relationship between PA and gout risk was examined using multivariate logistic regression models. RESULTS: Total PA was markedly low among gout patients, relative to controls (p < 0.05). Based on the IPAQ categorical score, 38.2% exhibited "low," 26.8% "moderate," and 35.0% "high" PA among gout patients. In comparison, 12.4% performed "low," 53.8% "moderate," and 33.8% "high" PA among controls. Multivariate analysis revealed that, after adjustment of confounding factors, both low (OR 6.382) and high PA (OR 2.048) had a higher prevalence of gout, as compared to moderate PA. Moreover, we revealed that the male sex, age, HUA duration, serum uric acid, glycated hemoglobin, dyslipidemia history, and drinking status were also independent indicators of the prevalence of gout. Furthermore, stratification analyses revealed results consistent with our prior results. CONCLUSIONS: PA intensity was associated with the prevalence of gout among T2DM and HUA patients, and the lowest prevalence was achieved from moderate intensity PA. Key Points • PA intensity was associated with the prevalence of gout among T2DM and HUA patients. • The lowest prevalence of gout was achieved from moderate intensity PA.

Feasibility study of a novel digital template-guided flapless extraction for maxillary palatal impacted teeth.

OBJECTIVE: With the increasing maturity of 3D printing technology, the application of digital guide template in the extraction of impacted teeth has become more sophisticated. However, for maxillary palatal deeply impacted teeth, there still exist significant clinical challenges. This experiment introduces a novel digital guide template and innovatively employs a flapless technique to explore a minimally invasive approach for the extraction of palatal deeply impacted teeth. METHODS: This experiment included 40 patients diagnosed with palatal completely impacted teeth, randomly divided into an experimental group and a control group. The experimental group used the new digital guide template for flapless extraction, while the control group employed the traditional freehand flap technique. RESULTS: The experimental group can significantly reduce the localization time of palatally impacted teeth (P < 0.001), with total surgery times of 18.15 ± 4.88 min and 22.00 ± 7.71 min for the experimental and control groups, respectively (P = 0.067). Although there were no significant statistical differences between the two groups in terms of intraoperative bleeding, adjacent tooth damage, infection, or damage to nearby important anatomical structures, the experimental group showed significant improvements in postoperative pain (P < 0.05), swelling (P < 0.001), and patient satisfaction (P < 0.001) compared to the control group. CONCLUSION: Compared to traditional freehand flap surgery, flapless extraction of palatally impacted teeth guided by digital templates significantly reduces the localization time of impacted teeth and demonstrates notable advantages in some postoperative complications. Future studies with larger sample sizes are needed to substantiate the feasibility of this technique.

Listeria-vectored cervical cancer vaccine candidate strains reduce MDSCs via the JAK-STAT signaling pathway.

BACKGROUND: Immunosuppressive status is prevalent in cancer patients and increases the complexity of tumor immunotherapy. It has been found that Listeria-vectored tumor vaccines had the potential ability of two-side regulatory effect on the immune response during immunotherapy. RESULTS: The results show that the combined immunotherapy with the LM∆E6E7 and LI∆E6E7, the two cervical cancer vaccine candidate strains constructed by our lab, improves the antitumor immune response and inhibits the suppressive immune response in tumor-bearing mice in vivo, confirming the two-sided regulatory ability of the immune response caused by Listeria-vectored tumor vaccines. The immunotherapy reduces the expression level of myeloid-derived suppressor cells (MDSCs)-inducing factors and then inhibits the phosphorylation level of STAT3 protein, the regulatory factor of MDSCs differentiation, to reduce the MDSCs formation ability. Moreover, vaccines reduce the expression of functional molecules associated with MDSCs may by inhibiting the phosphorylation level of the JAK1-STAT1 and JAK2-STAT3 pathways in tumor tissues to attenuate the immunosuppressive function of MDSCs. CONCLUSIONS: Immunotherapy with Listeria-vectored cervical cancer vaccines significantly reduces the level and function of MDSCs in vivo, which is the key point to the destruction of immunosuppression. The study for the first to elucidate the mechanism of breaking the immunosuppression.

[Immunoadjuvant Effect of Chitosan Oligosaccharide and Its Feasibility of Being Used as an Adjuvant for Attenuated Live Bacteria Vector Vaccines]. / å£³å¯¡ç³–çš„å ç–«ä½å‰‚æ•ˆæžœåŠä½œä¸ºå‡æ¯’æ´»èŒè½½ä½“ç–«è‹—ä½å‰‚çš„å¯è¡Œæ€§æŽ¢ç´¢.

Objective: To study the immunoadjuvant effects of chitosan oligosaccharide (COS), including the immune activation and the triggering of lysosomal escape, and to explore whether COS can be used as an adjuvant for attenuated live bacteria vector vaccines. Methods: 1) Mouse macrophages RAW264.7 cells were cultured with COS at 0 mg/mL (the control group) and 0.1-4 mg/mL for 24 h and the effect on cell viability was measured by CCK8 assay. Mouse macrophages RAW264.7 were treated with COS at 0 (the control group), 1, 2, and 4 mg/mL for 24 h. Then, the mRNA expression levels of the cytokines, including IFN-γ, IL-10, TGF-ß, and TLR4, were determined by RT-qPCR assay. 2) RAW264.7 cells were treated with 1 mL of PBS containing different components, including calcein at 50 µg/mL, COS at 2 mg/mL, and bafilomycin A1, an inhibitor, at 1 µmol/mL, for culturing. The cells were divided into the Calcein group, Calcein+COS group, and Calcein+COS+Bafilomycin A1 group accordingly. Laser scanning confocal microscopy was used to observe the phagocytosis and the intracellular fluorescence distribution of calcein, a fluorescent dye, in RAW264.7 cells in the presence or absence of COS intervention to determine whether COS was able to trigger lysosomal escape. 3) LM∆E6E7 and LI∆E6E7, the attenuated Listeria vector candidate therapeutic vaccines for cervical cancer, were encapsulated with COS at the mass concentrations of 0.5 mg/mL, 1 mg/mL, 2 mg/mL , 4 mg/mL, and 8 mg/mL. Then, the changes in zeta potential were measured to select the concentration of COS that successfully encapsulated the bacteria. Phagocytosis of the vaccine strains by RAW264.7 cells was measured before and after LM∆E6E7 and LI∆E6E7 were coated with COS at 2 mg/mL. Results: 1) CCK8 assays showed that, compared with the findings for the control group, the intervention of RAW264.7 cells with COS at different concentrations for 24 h was not toxic to the cells and promoted cell proliferation, with the difference being statistically significant (P<0.05). According to the RT-qPCR results, compared with those of the control group, the COS intervention up-regulated the mRNA levels of TLR4 and IFN-γ in RAW264.7 cells, while it inhibited the mRNA expression levels of TGF-ß and IL-10, with the most prominent effect being observed in the 4 mg/mL COS group (P<0.05). 2) Laser scanning confocal microscopy revealed that the amount of fluorescent dye released from lysosomes into the cells was greater in the Calcein+COS group than that in the Calcein group. In other words, a greater amount of fluorescent dye was released from lysosomes into the cells under COS intervention. Furthermore, this process could be blocked by bafilomycin A1. 3) The zeta potential results showed that COS could successfully encapsulate the surface of bacteria when its mass concentration reached 2 mg/mL. Before and after the vaccine strain was encapsulated by COS, the phagocytosis of LM∆E6E7 by RAW264.7 cells was 5.70% and 22.00%, respectively, showing statistically significant differences (P<0.05); the phagocytosis of LI∆E6E7 by RAW264.7 cells was 1.55% and 6.12%, respectively, showing statistically significant differences (P<0.05). Conclusion: COS has the effect of activating the immune response of macrophages and triggering lysosomal escape. The candidates strains of coated live attenuated bacterial vector vaccines can promote the phagocytosis of bacteria by macrophages. Further research is warranted to develop COS into an adjuvant for bacterial vector vaccine.

Discovery of a triphenylamine-based ligand that targets mitochondrial DNA G-quadruplexes and activates the cGAS-STING immunomodulatory pathway.

Stabilization of G-quadruplex (G4) structures in mitochondria leads to the damage of mitochondrial DNA (mtDNA), making mtDNA G4s a promising target in the field of cancer therapy in recent years. Damaged mtDNA released into the cytosol can stimulate cytosolic DNA-sensing pathways, and cGAS-STING pathway is a typical one with potent immunostimulatory effects. A few small molecule ligands of mtDNA G4s are identified with antitumor efficacy, but little is known about their results and mechanisms on immunomodulation. In this study, we engineered a series of triphenylamine-based analogues targeting mtDNA G4s, and A6 was determined as the most promising compound. Cellular studies indicated that A6 caused severe mtDNA damage. Then, damaged mtDNA stimulated cGAS-STING pathway, resulting in the following cytokine production of tumor cells and the maturation of DCs. In vivo experiments certified that A6 exerted suppressive influences on tumor growth and metastasis in 4T1 cell-bearing mice by the regulation of TME, including the remodeling of macrophages and the activation of T cells. To our knowledge, it is the first time to report a ligand targeting mtDNA G4s to activate the cGAS-STING immunomodulatory pathway, providing a novel strategy for the future development of mtDNA G4-based antitumor agents.

Dietary Supplementation of Astragalus membranaceus Extract Affects Growth Performance, Antioxidant Capacity, Immune Response, and Energy Metabolism of Largemouth Bass (Micropterus salmoides).

The present study investigated the effects of Astragalus membranaceus extract (AME) on growth performance, immune response, and energy metabolism of juvenile largemouth bass (Micropterus salmoides). Seven diets containing 0%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, and 0.6% AME (Con, AME0.1, AME0.2, AME0.3, AME0.4, AME0.5, and AME0.6 groups) were formulated and fed to M. salmoides for 8 weeks. Final body weight (FBW), feed intake (FI), weight gain (WG), and specific growth rate (SGR) were all significantly higher in AME0.4 group than in Con group (P < 0.05). Feed conversion rate (FCR) was significantly improved in AME0.5 group compared with Con group (P < 0.05). Whole-body crude protein contents were significantly increased in AME0.2 group (P < 0.05). Whole-body crude lipid contents were significantly lower in AME0.2 and AME0.3 groups, while muscle lipid was upregulated by dietary AME (P < 0.05). Hepatic malondialdehyde (MDA) contents were significantly lowered in AME0.3 and AME0.4 groups, and catalase (CAT) activities were significantly increased in AME0.1 and AME0.2 groups (P < 0.05). Plasma aspartate aminotransferase (AST) level was significantly lowered in AME0.5, and AME0.6 groups, and alanine aminotransferase (ALT) level was lowered in AME0.5 groups (P < 0.05). Plasma triglyceride was declined in AME0.6 group, and glucose was decreased by 0.3%-0.5% AME (P < 0.05). Significantly higher hepatocyte diameter, lamina propria width, and submucosal layer thickness were recorded in AME0.6 groups, while the longest villi height was obtained in AME0.2 and AME0.3 groups (P < 0.05). The mRNA expression levels of insulin-like growth factor 1 (igf1) revealed the growth-promoting effect of AME. The anti-inflammatory and antiapoptotic effects of AME were demonstrated by transcription levels of interleukin 8 (il-8), tumor necrosis factor-alpha (tnf-a), caspase, B-cell lymphoma-xl (Bcl-xl), bcl-2 associated x (Bax), and bcl-2-associated death protein (Bad). The transcription levels of lipid metabolism and gluconeogenesis related genes, including acetyl-CoA carboxylase alpha (acc1), fatty acid synthase (fasn), fatty acid binding protein 1 (fabp1), phosphoenolpyruvate carboxykinase 2 (pepck2), and glucose-6-phosphatase catalytic subunit 1a (g6pc), were reduced by AME treatment, while the levels of glycolysis-related genes, including glucokinase (gck) and pyruvate kinase (pk), were the highest in AME0.2 and AME0.3 groups (P < 0.05). According to polynomial regression analysis of SGR, WG, FCR, whole-body crude lipid, MDA, and ALT, the optimal AME supplementation level was estimated to be 0.320%-0.429% of the diet. These results provided insights into the roles of AME in regulating immunity and metabolism, which highly indicated its potential as immunostimulants and metabolic regulators in diverse aquatic animals.

Preimmunization with Listeria-vectored cervical cancer vaccine candidate strains can establish specific T-cell immune memory and prevent tumorigenesis.

BACKGROUND: Although HPV prophylactic vaccines can provide effective immune protection against high-risk HPV infection, studies have shown that the protective effect provided by them would decrease with the increased age of vaccination, and they are not recommended for those who are not in the appropriate age range for vaccination. Therefore, in those people who are not suitable for HPV prophylactic vaccines, it is worth considering establishing memory T-cell immunity to provide long-term immune surveillance and generate a rapid response against lesional cells to prevent tumorigenesis. METHODS: In this study, healthy mice were preimmunized with LM∆E6E7 and LI∆E6E7, the two Listeria-vectored cervical cancer vaccine candidate strains constructed previously by our laboratory, and then inoculated with tumor cells 40 d later. RESULTS: The results showed that preimmunization with LM∆E6E7 and LI∆E6E7 could establish protective memory T-cell immunity against tumor antigens in mice, which effectively eliminate tumor cells. 60% of mice preimmunized with vaccines did not develop tumors, and for the remaining mice, tumor growth was significantly inhibited. We found that preimmunization with vaccines may exert antitumor effects by promoting the enrichment of T cells at tumor site to exert specific immune responses, as well as inhibiting intratumoral angiogenesis and cell proliferation. CONCLUSION: Altogether, this study suggests that preimmunization with LM∆E6E7 and LI∆E6E7 can establish memory T-cell immunity against tumor antigens in vivo, which provides a viable plan for preventing tumorigenesis and inhibiting tumor progression.

An age classification model based on DNA methylation biomarkers of aging in human peripheral blood using random forest and artificial neural network.

Recent epigenetic studies have revealed a strong association between DNA methylation and aging and lifespan, which changes (increases or decreases) with age. Based on these, the construction of age prediction models associated with DNA methylation levels can be used to infer biological ages closer to the functional state of the organism. We downloaded methylation data from the Gene Expression Omnibus (GEO) public database for normal peripheral blood samples from people of different ages. We grouped the samples according to age (18-35 years and >50 years), screened the methylation sites that differed between the two groups, identified 44 differentially methylated sites, and subsequently obtained 11 age-related characteristic methylation sites using the random forest method. Then, we constructed an age classification model with these 11 characteristic methylation sites using an artificial neural network and evaluated its efficacy. The age classification model was constructed by an artificial neural network and its efficacy was evaluated. The model predicted an area under the curve (AUC) of 0.97 in the validation set and accurately distinguished between those aged 18-35 and >50 years. Furthermore, the levels of these 11 characteristic methylation sites also differed significantly between the two sets of samples in the validation set, including six newly identified age-related methylation sites (P<0.001). Finally, we constructed a multifactor regulatory network based on the corresponding genes of age-related methylation sites to reveal the transcriptional and post-transcriptional regulation patterns. As a result of the increasing problem of aging, the age classification model we constructed allows us to accurately distinguish different age groups at the molecular level, which will be more predictive than chronological age for assessing individual aging and future health status.

Efficacy and Mechanism of Highly Active Umbilical Cord Mesenchymal Stem Cells in the Treatment of Osteoporosis in Rats.

Background: Osteoporosis increases bone brittleness and the risk of fracture. Umbilical cord mesenchymal stem cell (UCMSC) treatment is effective, but how to improve the biological activity and clinical efficacy of UCMSCs has not been determined. METHODS: A rat model of osteoporosis was induced with dexamethasone sodium phosphate. Highly active umbilical cord mesenchymal stem cells (HA-UCMSCs) and UCMSCs were isolated, cultured, identified, and infused intravenously once at a dose of 2.29 × 106 cells/kg. In the 4th week of treatment, bone mineral density (BMD) was evaluated via cross-micro-CT, tibial structure was observed via HE staining, osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs) was examined via alizarin red staining, and carboxy-terminal cross-linked telopeptide (CTX), nuclear factor-κß ligand (RANKL), procollagen type 1 N-terminal propeptide (PINP) and osteoprotegerin (OPG) levels were investigated via enzyme-linked immunosorbent assays (ELISAs). BMMSCs were treated with 10-6 mol/L dexamethasone and cocultured with HA-UCMSCs and UCMSCs in transwells. The osteogenic and adipogenic differentiation of BMMSCs was subsequently examined through directional induction culture. The protein expression levels of WNT, ß-catenin, RUNX2, IFN-γ and IL-17 in the bone tissue were measured via Western blotting. RESULTS: The BMD in the healthy group was higher than that in the model group. Both UCMSCs and HA-UCMSCs exhibited a fusiform morphology; swirling growth; high expression of CD73, CD90 and CD105; and low expression of CD34 and CD45 and could differentiate into adipocytes, osteoblasts and chondrocytes, while HA-UCMSCs were smaller in size; had a higher nuclear percentage; and higher differentiation efficiency. Compared with those in the model group, the BMD increased, the bone structure improved, the trabecular area, number, and perimeter increased, the osteogenic differentiation of BMMSCs increased, RANKL expression decreased, and PINP expression increased after UCMSC and HA-UCMSC treatment for 4 weeks. Furthermore, the BMD, trabecular area, number and perimeter, calcareous nodule counts, and OPG/RANKL ratio were higher in the HA-UCMSC treatment group than in the UCMSC treatment group. The osteogenic and adipogenic differentiation of dexamethasone-treated BMMSCs was enhanced after the coculture of UCMSCs and HA-UCMSCs, and the HA-UCMSC group exhibited better effects than the UCMSC coculture group. The protein expression of WNT, ß-catenin, and runx2 was upregulated, and IFN-γ and IL-17 expression was downregulated after UCMSC and HA-UCMSC treatment. CONCLUSION: HA-UCMSCs have a stronger therapeutic effect on osteoporosis compared with that of UCMSCs. These effects include an improved bone structure, increased BMD, an increased number and perimeter of trabeculae, and enhanced osteogenic differentiation of BMMSCs via activation of the WNT/ß-catenin pathway and inhibition of inflammation.

Effects of Low-Fish-Meal Diet Supplemented with Coenzyme Q10 on Growth Performance, Antioxidant Capacity, Intestinal Morphology, Immunity and Hypoxic Resistance of Litopenaeus vannamei.

The aim of this study was to evaluate the effects of a low-fish-meal diet supplemented with coenzyme Q10 on the growth, antioxidant capacity, immunity, intestinal health and hypoxic resistance of Litopenaeus vannamei. L.vannamei with an initial weight of 0.66 g were fed with the experimental diets for 56 days. Diets D1 (20% FM level) and D2-D7 (15% FM level), supplemented with 0%, 0.002%, 0.004%, 0.006%, 0.008% and 0.01% coenzyme Q10 were formulated. In terms of growth performance, the weight gain and specific growth rate in the D2 diet were significantly lower than those in the D1 diet (p < 0.05). The final body weight, weight gain and specific growth rate in the D2-D7 diets had an upward trend, and the condition factor in the D2-D7 diets was lower than those in the D1 diet (p < 0.05). There were no significant differences in the crude protein and crude lipid levels in the whole body among all diet treatments (p > 0.05). In terms of hepatopancreas antioxidant parameters, the D5 and D6 diets significantly promoted the total antioxidant capacity and total superoxide dismutase activity, and significantly decreased the malondialdehyde content (p < 0.05). The expression levels of cat, mnsod and gpx in shrimp fed with the D5 and D6 diets were significantly higher than those of shrimp fed with the D2 diet (p < 0.05). In addition, the mRNA level of ProPO was increased in the D4 and D5 diets, and LZM expression was increased in the D6 diet compared with the D1 diet (p < 0.05). The villus height of shrimp fed with diets supplemented with coenzyme Q10 was significantly increased (p < 0.05), and the intestinal thickness and submucosal thickness of shrimp fed with the D6 diet were the highest (p < 0.05). After acute hypoxia stress, lethal dose 50 time in the D3-D7 diets was significantly increased compared with the D1 and D2 diets (p < 0.05), and the highest value was found in the D4 diet (p < 0.05). After stress, the expression levels of TLR pathway-related genes (Toll, Myd88, Pelle, TRAF6 and Dorsal) in the D4 and D6 diets were significantly increased compared with the D2 diet. In general, Litopenaeus vannamei fed with the D6 diet achieved the best growth, antioxidant capacity, immunity, and intestinal morphology among all low FM diets and D4-D6 diets improved hypoxic resistance.

Correction: Dietary L-tryptophan alleviated LPS-induced intestinal barrier injury by regulating tight junctions in a Caco-2 cell monolayer model.

Correction for 'Dietary L-tryptophan alleviated LPS-induced intestinal barrier injury by regulating tight junctions in a Caco-2 cell monolayer model' by Mengdie Chen et al., Food Funct., 2019, 10, 2390-2398, https://doi.org/10.1039/C9FO00123A.

Association between Age at Type 2 Diabetes Onset and Diabetic Retinopathy: A Double-Center Retrospective Study.

Background: With the decreasing age of type 2 diabetes mellitus (T2DM) onset, the incidence of diabetic complications is gradually increasing. We evaluated the independent effect of age at diabetes onset on diabetic retinopathy (DR) development. Methods: A total of 7472 patients with T2DM were enrolled in the National Metabolic Management Center from September 2017 to May 2022. Anthropometry data, laboratory reports, and medical history were collected. The independent association of DR with age at diabetes onset was analyzed using multivariable logistic regression models. In addition, a stratified analysis was performed to determine the effect of confounding variables. Results: Of the 7472 patients recruited, 1642 (21.98%) had DR. Patients with DR had considerably younger ages of diabetes onset than those without DR (45 (38-53) years vs. 50 (43-57) years, P < 0.001). The proportion of patients with T2DM onset at a younger age was higher in the DR group than that in the non-DR group. Participants were divided into four groups according to their age at diabetes onset, namely, ≥60, <40, 40-49, and 50-59 years. Compared with patients with diabetes onset at age ≥ 60 years, those with diabetes onset at <40 years (odds ratio (OR): 5.56, 95% confidence interval (CI): 3.731-8.285, P < 0.001), 40-49 years (OR: 2.751, 95% CI: 2.047-3.695, P < 0.001), and 50-59 years (OR: 1.606, 95% CI: 1.263-2.042, P < 0.001) were at an increased risk of DR after adjusting for potential confounding factors. Furthermore, stratification analyses demonstrated that young age at diabetes onset is an independent risk factor for DR. Conclusions: Compared with diabetes onset at an older age, diabetes onset at a younger age is associated with a significantly increased DR risk.

[Listeria Balanced Lethal Systems Expressing Cervical Cancer Antigen Genes: Construction and Basic Biological Characteristics]. / è¡¨è¾¾å®«é¢ˆç™ŒæŠ—åŽŸåŸºå› çš„æŽæ–¯ç‰¹èŒå¹³è¡¡è‡´æ­»ç³»ç»Ÿçš„æž„å»ºåŠå ¶ç”Ÿç‰©å­¦ç‰¹æ€§ç ”ç©¶.

Objective: To construct Listeria monocytogenes (LM) and Listeria ivanovii (LI) balanced lethal systems expressing cervical cancer antigens, to study their basic biological characteristics, and to provide reference data for the immunotherapy of cervical cancer. Methods: Through seamless cloning via in vitro ligation kit, the HPV16 E6E7 fusion protein antigen gene constructed in our lab was spliced to the complement plasmid pCWgfp-LM dal-Amp that contained the nutritional gene dal. Then, we replaced the ampicillin (Amp) resistance gene of the complement plasmid with the asd nutrition gene. The ligation reaction mixture was transformed into Escherichia coli (E. coli) recipient bacteria DH5αΔasd and the complement plasmid pCWgfp-E6E7-LM dal-Ampfree, which expressed cervical cancer antigens and had no Amp resistance, was obtained by nutrition screening from the E. coli DH5αΔasd. The plasmid pCWgfp-E6E7-LM dal-Ampfree was complemented into LMΔdd and LIΔdd, the attenuated nutrition-deficient Listeria strains with the virulence genes actA and plcB and nutrition genes dal and dat deleted by electroporation, thereby obtaining LM and LI balanced lethal systems expressing cervical cancer antigen genes. The in vitro growth of the strains was observed. Western blot was performed to examine the status of antigen protein expression. PCR was performed to measure the in vitro passage stability of complement plasmid pCWgfp-E6E7-LM dal-Ampfree. Their basic biological characteristics were examined by biochemical reaction tests and hemolysis assay. Results: Two Listeria balanced lethal systems expressing cervical cancer antigen were successfully constructed. The HPV16 type E6E7 fusion protein was successfully expressed in the two Listeria balanced lethal systems. pCWgfp-E6E7-LM dal-Ampfree, the positive plasmid expressing cervical cancer antigen, maintained stable existence in the two Listeria balanced lethal systems. The two Listeria balanced lethal systems expressing cervical cancer antigen showed significantly better recovery growth in comparison with Listeria nutrition deficiency strains. The results of biochemical reaction tests showed that most of the biochemical reaction of the two Listeria balanced lethal systems expressing cervical cancer antigen were consistent with those of Listeria attenuated strains. The two Listeria balanced lethal systems expressing cervical cancer antigen still maintained the hemolytic ability, although their hemolytic ability was slightly inferior to that of the Listeria balanced lethal systems not expressing cervical cancer antigen and the Listeria attenuated strains. Conclusion: The two Listeria balanced lethal systems expressing cervical cancer antigen genes are constructed successfully. They display normal in vitro growth. The complement plasmid pCWgfp-E6E7-LM dal-Ampfree can maintain stable existence in vitro, showing little change in its biochemical characteristics and hemolytic ability. Further research should be conducted to investigate the potential of these two recombinant strains to be used as candidate strains for cervical cancer therapeutic vaccine.

Effects of Barranca yajiagengensis Powder in the Diet of Trachinotus ovatus on the Growth Performance, Antioxidant Capacity, Immunity and Morphology of the Liver and Intestine.

Barranca yajiagengensis, a novel filamentous microalga, can accumulate lutein under high-light and low-nitrogen conditions. It is well known that lutein has antioxidant, anti-inflammatory and immune-modulating properties. The purpose of this study is to evaluate the effects of including lutein-rich B. yajiagengensis powder in the diet of Trachinotus ovatus on the growth performance, antioxidant capacity, immunity, liver, and intestinal morphology. For this aim, three experimental diets containing 0% (BY0), 1% (BY1), and 5% (BY5) B. yajiagengensis powder were formulated for six-week feeding trials. The results indicated that growth performance, feed utilization, and intestinal morphology were not affected by different diet treatments. Fish fed with the BY5 diet promoted antioxidant ability by activating the Nrf2-ARE signal pathway and enhancing antioxidant enzymes activities. Furthermore, the BY5 diet improved non-specific immunity and antibacterial ability by activating lysozymes and the complement system and increasing the nitric oxide (NO) content and total nitric oxide synthase activity. Dietary B. yajiagengensis supplementation improved the liver morphology and exerted hepatoprotective effects. Therefore, as a natural source of lutein, B. yajiagengensis has the potential as a safe and non-toxic immunostimulant for T. ovatus. A diet supplemented with 5% B. yajiagengensis is recommended to improve the growth, antioxidant capacity, immune response, and liver health of T. ovatus.

The structure-based optimization of δ-sultone-fused pyrazoles as selective BuChE inhibitors.

Structure-based optimization was conducted to improve the potency and selectivity of BuChE inhibitors with δ-sulfonolactone-fused pyrazole scaffold. By mimicking the hydrophobic interactions of donepezil at PAS, the introduction of a tertiary benzylamine at 5-position can significantly increase BuChE inhibitory activity. Compounds C4 and C6 were identified as high selective nanomolar BuChE inhibitors (IC50 = 8.3 and 7.7 nM, respectively), which exhibited mild antioxidant capacity, nontoxicity, lipophilicity and neuroprotective activity. Kinetic studies showed that BuChE inhibition of compound C6 was mixed-type against BuChE (Ki = 24 nM) and >2000-fold selectivity for BuChE over AChE. The proposed binding mode of new inhibitors was consistent with the results of structure-activity relationship analysis.