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ABSTRACT Aims/Introduction The coronary physiology and prognosis of patients with different hemoglobin A1c (HbA1c) levels after percutaneous coronary intervention (PCI) are currently unknown. The aim of this study was to assess the effect of different levels of HbA1c control on coronary physiology in patients who underwent PCI for coronary heart disease combined with type 2 diabetes mellitus by quantitative flow ratio (QFR). Materials and Methods Patients who successfully underwent PCI and completed 1‐year coronary angiographic follow up were enrolled, clinical data were collected, and QFR at immediate and 1‐year follow up after PCI was retrospectively analyzed. A total of 257 patients (361 vessels) were finally enrolled and divided into the hemoglobin A1c (HbA1c)‐compliance group (103 patients, 138 vessels) and non‐HbA1c‐compliance group (154 patients, 223 vessels) according to the HbA1c cut‐off value of 7%. We compared the results of QFR analysis and clinical outcomes between the two groups. Results At 1‐year follow up after PCI, the QFR was significantly higher (0.94 ± 0.07 vs 0.92 ± 0.10, P = 0.019) and declined less (0.014 ± 0.066 vs 0.033 ± 0.095, P = 0.029) in the HbA1c‐compliance group. Meanwhile, the incidence of physiological restenosis was lower in the HbA1c‐compliance group (2.9% vs 8.5%, P = 0.034). Additionally, the target vessel revascularization rate was lower in the HbA1c‐compliance group (6.8% vs 16.9%, P = 0.018). Furthermore, HbA1c ≥7% (OR 2.113, 95% confidence interval 1.081–4.128, P = 0.029) and QFR decline (OR 2.215, 95% confidence interval 1.147–4.277, P = 0.018) were independent risk factors for target vessel revascularization. Conclusion Patients with well‐controlled HbA1c levels have better coronary physiological benefits and the incidence of adverse clinical outcome events might be reduced.

Abstract Background The nucleus accumbens (Nac) is a crucial brain region in the pathophysiology of major depressive disorder (MDD) patients with anhedonia. However, the relationship between the functional imaging characteristics of Nac subregions and anhedonia remains unclear. Thus, this study aimed to investigate the role of resting-state functional connectivity (rsFC) of the Nac subregions between MDD and anhedonia. Methods We performed resting-state functional magnetic resonance imaging (fMRI) to measure the rsFC of Nac subregions in 55 MDD patients and 30 healthy controls (HCs). A two-sample t test was performed to determine the brain regions with varying rsFC among Nac subregions between groups. Then, correlation analyses were carried out to investigate the relationships between the aberrant rsFC of Nac subregions and the severity of anhedonia. Furthermore, we constructed a mediation model to explain the role of the aberrant rsFC of Nac subregions between MDD and the severity of anhedonia. Results Compared with the HC group, decreased rsFC of Nac subregions with regions of the prefrontal cortex, insula, lingual gyrus, and visual association cortex was observed in MDD patients. In the MDD group, the rsFC of the right Nac shell-like subregions with the middle frontal gyrus (MFG)/superior frontal gyrus (SFG) was correlated with consummatory anhedonia, and the rsFC of the Nac core-like subdivisions with the inferior frontal gyrus (IFG)/insula and lingual gyrus/visual association cortex was correlated with anticipatory anhedonia. More importantly, the functional alterations in the Nac subregions mediated the association between anhedonia and depression. Conclusions The present findings suggest that the functional alteration of the Nac subregions mediates the association between MDD and anhedonia, which provides evidence for the hypothesis that MDD patients have neurobiological underpinnings of reward systems that differ from those of HCs.

Clear cell renal cell carcinoma (ccRCC), the most common malignant subtype of renal cell carcinoma, is characterized by the accumulation of lipid droplets in the cytoplasm. RNASET2 is a protein coding gene with a low expression level in ovarian cancers, but it is overexpressed in poorly differentiated neuroendocrine carcinomas. There is a correlation between RNASET2 upregulation and triglyceride expression levels in human serum but is unknown whether such an association is a factor contributing to lipid accumulation in ccRCC. Herein, we show that RNASET2 expression levels in ccRCC tissues and cell lines are significantly higher than those in both normal adjacent tissues and renal tubular epithelial cells. Furthermore, its upregulation is associated with increases in ccRCC malignancy and declines in patient survival. We also show that an association exists between increases in both cytoplasmic lipid accumulation and HIF‐2α transcription factor upregulation, and increases in both RNASET2 and triglyceride expression levels in ccRCC tissues. In addition, DGAT1 and DGAT2, two key enzymes involved in triglyceride synthesis, are highly expressed in ccRCC tissues. By contrast, RNASET2 knockdown inhibited their expression levels and lowered lipid droplet accumulation, as well as suppressing in vitro cell proliferation, cell invasion, and migration. In conclusion, our data suggest HIF2α upregulates RNASET2 transcription in ccRCC cells, which promotes both the synthesis of triglycerides and ccRCC migration. As such, RNASET2 may have the potential as a biomarker or target for the diagnosis and treatment of ccRCC.

Abstract Background The precise pathogenesis of poor endometrial receptivity in recurrent implantation failure (RIF) remains unclear. This study was aimed at exploring the effects of different CD44 isoforms in the mid-secretory phase endometrium on endometrial receptivity in women with RIF. Methods Mid-secretory phase endometrial tissue samples were obtained from the following two groups of women who had undergone IVF: (a) 24 patients with RIF and (b) 18 patients with infertility due to tubal obstruction, who had achieved a successful clinical pregnancy after the first embryo transfer in IVF (control group). Identification of differentially expressed CD44 isoforms in endometrial tissues was assessed using immunohistochemistry, qPCR, and western blotting. Effects of overexpression and knockdown of CD44v3 on proliferation and decidualization of immortalized human endometrial stromal cells (T-HESCs) and primary HESCs were investigated by qPCR and western blot analysis. A heterologous coculture system of embryo implantation was constructed to mimic the process of trophoblast invasion during implantation. Results The expression of CD44v3 was significantly higher in the mid-secretory phase of endometrial stromal cells than in the proliferation phase, but was notably lower in RIF patients. Knockdown of CD44v3 significantly downregulated cell proliferation both in T-HESCs and HESCs. The expression of decidualization markers, prolactin (PRL) and insulin like growth factor binding protein-1 (IGFBP1), was notably decreased following the knockdown of CD44v3, whereas the expression of both PRL and IGFBP1 increased after its overexpression in HESCs. Furthermore, the CD44v3-knockdown HESCs displayed significant deficiency in supporting trophoblast outgrowth in a coculture system of embryo implantation; however, overexpression of CD44v3 in HESCs promoted trophoblast outgrowth. Conclusion The reduced expression of CD44v3 suppresses the proliferation and decidualization of HESCs, which might play a pivotal role in poor endometrial receptivity in women with RIF.

Abstract Background Mammalian sperm maturation in the epididymis is mainly modulated by exosomes that are secreted into the epididymal lumen from epididymal epithelial cells (EECs). Exposure to oxidative stress (OS) resulting from being fed a high fat diet (HFD) reduces sperm fertility, which is one of the cause inducing male infertility. Thus, we hypothesize that stress-induced changes in exosome content play a critical role in mediating this detrimental process. Methods An obese mouse model was established by feeding a HFD. Then oxidative stress status was measured in the mouse caput epididymis, epididymal fluid and spermatozoa. Meanwhile, epididymis-derived purified exosomes were isolated and validated. Subsequently, liquid chromatography tandem mass spectrometry (LC-MS) was used to perform proteomic analysis of purified exosomes. Gene Ontology (GO) analysis was performed along with pathway enrichment to identify differentially expressed proteins (DEPs). Results Two hundred and two DEPs mostly related to endoplasmic reticulum (ER) function were identified in the exosomes separated from the epididymis of control mice and obese mice. The ER stress and CD63 (an exosome marker), both increased in the caput epididymis of obese mice. Furthermore, an in vitro study showed that palmitic acid (PA), an-oxidative stress inducer, increased exosome biogenesis and secretion in the EECs. Conclusion Oxidative stress in the epididymal microenvironment induces ER stress in the EECs. This effect alters the epididymis-derived exosome content, profile and amounts of their differentially expressed ER proteins. Such changes may affect exosome biogenesis and cargo packaging, finally leading to abnormalities in sperm maturation and fertility.

Abstract Background Premature ovarian insufficiency (POI) is a refractory disease that seriously affects the reproductive health of women and is increasing in incidence and prevalence globally. There is enormous demand to improve fertility in women with POI, while there is still lack of effective therapeutic methods in clinic. Cell-free fat extract (CEFFE) has been reported to contain thousands of active proteins which possess the ability to promote tissue repair in other diseases. In our study, we aimed to observe the efficacy and biosecurity of CEFFE on the repair of ovarian function and fertility of mice with POI and further explore the underlying mechanism. Methods In vivo, POI mice model, established by cyclophosphamide (CTX, 120 mg/kg) and busulfan (BUS, 12 mg/kg), was treated with CEFFE via the tail vein every two days for 2 weeks. Then, the weight of ovaries, estrous cycle and follicle count by H&E staining were measured. The content of AMH, E2 and FSH in serum was measured by Enzyme-linked immunosorbent assay. Fertility was evaluated by the number of oocytes retrieved, the development of embryos in vitro and the litter size. Biosecurity of parent mice and their pups were examined by body mass and visceral index. The proliferation and apoptosis of cells in ovaries were examined by immunohistochemistry and transmission electron microscopy. Furthermore, the mRNA-Seq of mouse ovarian granulosa cells was performed to explore underlying mechanism of CEFFE. In vitro, KGN cell line and human primary ovarian granulosa cells (hGCs) were treated with 250 μM CTX for 48 h with/without CEFFE. The proliferative ability of cells was detected by cell counting kit-8 assay (CCK-8) and EDU test; the apoptosis of cells was detected by TUNEL and flow cytometry. Results CEFFE recovered the content of AMH, E2 and FSH in serum, increased the number of follicles and the retrieved oocytes of POI mice (P

Objective. To investigate the serum levels of CXC chemokine 13 (CXCL-13), retinol binding protein-4 (RBP-4), and interleukin 6 (IL-6) in patients with Graves’ disease (GD). The correlation between CXCL-13, RBP-4, and IL-6 levels and the basal metabolic rate (BMR) was analyzed. Methods. 118 GD patients diagnosed in our hospital were selected as the observation group from March 2017 to December 2018. According to the measured BMR value, 118 GD patients were divided into the mild group (n = 39), the moderate group (n = 47), and the severe group (n = 32), three subgroups. 60 healthy subjects were selected as the control group. The serum levels of CXCL-13, RBP-4, IL-6, TSH, FT3, and FT4 in every group were measured. Pearson correlation analysis was used to observe the correlation of serum CXCL-13, RBP-4, and IL-6 levels with TSH, FT3, FT4, and BMR. Results. The levels of serum CXCL-13, RBP-4, and IL-6 in the observation group were higher than those of the control group, and the differences were statistically significant (P

The treatment of radioactive wastewater is one of the major problems in the current research. With the development of nuclear energy, the efficient removal of 99TcO4− in radioactive wastewater has attracted the attention of countries all over the world. In this study, a novel functional polyamide polymer p-(Amide)-PAM was synthesized by the two-step method. The experimental results show that p-(Amide)-PAM has good adsorptive properties for 99TcO4−/ReO4− and has good selectivity in the nitric acid system. The kinetics of the reaction of p-(Amide)-PAM with 99TcO4−/ReO4− was studied. The results show that p-(Amide)-PAM has a fast adsorption rate for 99TcO4−/ReO4−, the saturated adsorption capacity reaches 346.02 mg/g, and the material has good reusability. This new polyamide-functionalized polyacrylamide polymer material has good application prospects in the removal of 99TcO4− from radioactive wastewater.

Abstract Background Obesity is a worldwide crisis impairing human health. In this condition, declines in sperm quality stem from reductions in sperm concentration, motility and increase in sperm deformity. The mechanism underlying these alterations remains largely unknown. This study, determined if obesity-associated proteomic expression patterns in mice sperm parallel those in spermatozoa obtained from obese humans. Methods An obese mouse model was established via feeding a high-fat diet (HFD). Histological analysis identified testicular morphology and a computer assisted semen analyzer (CASA) evaluated sperm parameters. Proteome analysis was performed using a label-free quantitative LC-MS/MS system. Western blot, immunohistochemical and immunofluorescent analyses characterized protein expression levels and localization in testis, sperm and clinical samples. Results Bodyweight gains on the HFD induced hepatic steatosis. Declines in sperm motility accompanied sperm deformity development. Differential proteomic analysis identified reduced cytoskeletal proteins, centrosome and spindle pole associated protein 1 (CSPP1) and Centrin 1 (CETN1), in sperm from obese mice. In normal weight mice, both CSPP1 and CETN1 were localized in the spermatocytes and spermatids. Their expression was appreciable in the post-acrosomal region parallel to the microtubule tracks of the manchette structure in spermatids, which affects spermatid head shaping and morphological maintenance. Moreover, CSPP1 was localized in the head–tail coupling apparatus of the mature sperm, while CETN1 expression was delimited to the post-acrosomal region within the sperm head. Importantly, sperm CSPP1 and CETN1 abundance in both the overweight and obese males decreased in comparison with that in normal weight men. Conclusion These findings show that regionally distinct expression and localization of CETN1 and CSPP1 is strongly related to spermiogenesis and sperm morphology maintaining. Obesity is associated with declines in the CETN1 and CSPP1 abundance and compromise of both sperm morphology in mice and relevant clinical samples. This parallelism between altered protein expression in mice and humans suggests that these effects may contribute to poor sperm quality including increased deformity.

Abstract Background Spermatogenesis is a complex process involving the self-renewal and differentiation of spermatogonia into mature spermatids in the seminiferous tubules. During spermatogenesis, germ cells migrate from the basement membrane to cross the blood-testis barrier (BTB) and finally reach the luminal side of the seminiferous epithelium. However, the mechanism for regulating the migration of germ cells remains unclear. In this study, we focused on the expression and function of transcriptional factor EB (TFEB), a master regulator of lysosomal biogenesis, autophagy and endocytosis, in spermatogenesis. Methods The expression pattern of the TFEB in mouse testes were investigated by Western blotting and immunohistochemistry analyses. Either undifferentiated spermatogonia or differentiating spermatogonia were isolated from testes using magnetic-activated cell sorting based on specific cell surface markers. Differentiation of spermatogonia was induced with 100 nM retinoic acid (RA). shRNA was used to knock down TFEB in cells. TFEB expression was detected by immunofluorescence, qRT-PCR, and Western blotting. Cell migration was determined by both transwell migration assay and wound healing assay applied to a cell line of immortalized spermatogonia, GC-1 cells. Results During testicular development, TFEB expression was rapidly increased in the testes at the period of 7 days post-partum (dpp) to 14 dpp, whereas in adult testis, it was predominantly localized in the nucleus of spermatogonia at stages VI to VIII of the seminiferous epithelial cycle. Accordingly, TFEB was observed to be mainly expressed in differentiating spermatogonia and was activated for nuclear translocation by RA treatment. Moreover, knockdown of TFEB expression by RNAi did not affect spermatogonial differentiation, but significantly reduced cell migration in GC-1 cells. Conclusion These findings imply that regionally distinct expression and activation of TFEB was strongly associated with RA signaling, and therefore may promote cell migration across the BTB and transport along the seminiferous epithelium.

An accurate and effective method combining ion chromatography (IC) and inductively coupled plasma optical emission spectrometry (ICP-OES) was applied in this work to qualitatively and quantitatively analyze individual and co-existing iodide (I−) and iodate (IO3−) at various concentrations. More specifically, a very strong linear relationship for the peak area for the co-existing I− and IO3− ions was reached, and a high resolution value between two peaks was observed, which proves the effectiveness of our combined IC-ICP-OES method at analyzing iodine species. We observed lower accessible porosity for the diffusion of both I− and IO3− in samples of bentonite clay using IC-ICP-OES detection methods, where the effective diffusion coefficient varied based on the anion exclusion effect and the size of the diffusing molecules. In fact, the distribution coefficients (Kd) of both I− and IO3− were close to 0, which indicates that there was no adsorption on bentonite clay. This finding can be explained by the fact that no change in speciation took place during the diffusion of I− and IO3− ions in bentonite clay. Our IC-ICP-OES method can be used to estimate the diffusion coefficients of various iodine species in natural environments.

Advection-dispersion experiments (ADE) were effectively designed for inadequate transport models through a calibration/validation process. HTO, selenium (Se), and cesium (Cs) transport in crushed granite were studied using a highly reliable, dynamic column device in order to obtain the retardation factors (R) and the dispersion coefficients (D) by fitting experimental breakthrough curves (BTCs) for various path lengths. In order to conduct a safety assessment (SA) of a deep geological repository for high-level radioactive waste, radionuclide transport in rock systems is necessary to clarify and establish a suitable model. A dynamic column with a radiotracer (HTO, Se(IV), and Cs) was applied to 2, 4, and 8 cm path lengths using a STANMOD simulation. The results showed similar results between the BTCs of Se and Cs by fitting a non-equilibrium sorption model due to the retardation effect. In fact, there was a relatively obvious sorption of Se and Cs in the BTCs obtained by fitting a retardation factor (R) value higher than 1. In addition, a two-region (physical) and a two-site (chemical) non-equilibrium model with either the lowest sum of squared residuals (SSQ) or the root mean square error (RMSE) were applied to determine the Se and Cs sorption mechanisms on granite.

Various numerical methods have been being extensively used to estimate the diffusion parameters of pertechnetate (99TcO4−) in compacted MX80 bentonite clay using through-diffusion (TD) techniques. In this study, an improved TD column test was applied, and the diffusion fluxes of tritium (HTO) as a non-reactive radionuclide, and 99TcO4− with various dry densities, were compared under the same experimental conditions. Similar results were obtained for the apparent diffusion coefficients of HTO and 99TcO4− using three estimation methods: a graphical method applying the asymptote calculation, an analytical solution using Lsqcurvefit installed in MATLAB, and the Marquardt–Levenberg optimization algorithm in the HYDRUS-1D inverse method. The statistical analysis showed that the densities using a one-way analysis of variance (ANOVA) for the three estimation methods ranged from 1200 to 2000 kg/m3, which indicated that there were no obvious differences between HTO and 99TcO4−. In general, the diffusion parameters of 99TcO4− were lower than those for HTO due to anion exclusion effects and lower accessible porosity.

Clay rock in the Tamusu (TMS) area in the Inner Mongolia province is one candidate as a geological disposal site for highly radioactive waste in China. The diffusion behavior of HTO and Se(IV) in Tamusu clay rock was studied by through-diffusion (TD) experiments and numerical analysis to determine the spatial and temporal variation. A minimum error analysis was conducted to determine the HTO and Se(IV) diffusion coefficients in compacted TMS clay. The TD experimental results and numerical analysis showed that the diffusion of HTO and Se reached a steady state within 7 and 50 days, respectively, and the apparent diffusion coefficients (Da) decreased with the increases in the compacted density. In fact, there was retardation of Se diffusion in intact TMS clay rock. A two-site sorption model for Se was applied to simulate fast and slow sorption behavior quantitatively.

Abstract The effect of obesity on diabetic retinopathy (DR) has been under scrutiny in recent years. The weight-adjusted waist index (WWI) has been reported to better assess the degree of centripetal obesity in humans, with a higher WWI indicating a higher amount of body fat. The present study is the first to investigate the relationship between WWI and DR and to assess the difference in the predictive ability of WWI and other obesity indices for DR. This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2008. Researchers collected complete anthropometric data (weight and waist circumference), dilated fundus images, and adult baseline information. Independent interactions between WWI and DR were investigated using multivariate regression and subgroup analyses. In addition, nonlinear associations and threshold effects between WWI and DR were searched for by smoothed curve fitting and by two-stage linear regression modeling. Finally, the receiver operating characteristic curve (ROC) was plotted to compare the predictive power of WWI with other indices of obesity for DR. A total of 1228 eligible patients with diabetes were collected in this study. There were 631 (51.38%) males and 597 (48.62%) females. Among them, 545 (44.38%) were without diabetic retinopathy, 555 (45.20%) had mild diabetic retinopathy, 100 (8.14%) had moderate/severe diabetic retinopathy and 28 (2.28%) had proliferative diabetic retinopathy (PDR). In the fully adjusted model, each unit increase in WWI was associated with a corresponding 31% reduction in the prevalence of DR [OR (95% CI) = 0.69 (0.58, 0.83)]. Compared with subjects in the lowest quartile (quartile 1), subjects in the highest quartile of WWI levels (quartile 4) were 45% less likely to have DR [OR (95% CI) = 0.55 (0.38, 0.78)]. In the case of female participants, a U-shaped correlation was observed between WWI and DR with an inflection point of 11.49. WWI also possesses a better predictive ability for DR compared to obesity indicators such as weight, BMI, and ABSI. This study showed a negative association between WWI and DR in the U.S. population aged 40 years and older.

IntroductionResveratrol (RSV) is a natural polyphenolic compound derived from a variety of plants that possesses a wide range of biological activities, including antioxidant, anti-inflammatory, antitumor, antibacterial, antiviral, anti-aging, anti-radiation damage, anti-apoptosis, immune modulation, regulation of glucolipid metabolism, inhibition of lipid deposition, and anti-neuro. It is therefore considered a promising drug with the potential to treat a wide range of diseases.MethodIn this study, using Web of Science Core Collection (WoSCC) and CiteSpace bibliometric tool, VOSviewer quantitatively visualized the number of countries, number of authors, number of institutions, number of publications, keywords, and references of 16,934 resveratrol-related papers from 2014–2023 for quantitative and qualitative analysis. ResultsThe results showed that an average of 1693.4 papers were published per year, with a general upward trend. China had the most publications with 5877. China Medical University was the institution with the largest number of publications and the highest number of citations in the field. The research team was mainly led by Prof. Richard Tristan, and the journal with the highest number of published papers was Molecular. Dietary polyphenols, oxidative stress, and antioxidant and anti-inflammatory effects are the most frequently cited articles. Oxidative stress, apoptosis, expression, and other keywords play an important role in connecting other branches of the field.DiscussionOur analysis indicates that the integration of nanoparticles with RSV is poised to become a significant trend. RSV markedly inhibits harmful bacteria, fosters the proliferation of beneficial bacteria, and enhances the diversity of the intestinal flora, thereby preventing intestinal flora dysbiosis. Additionally, RSV exhibits both antibacterial and antiviral properties. It also promotes osteogenesis and serves a neuroprotective function in models of Alzheimer's disease. The potential applications of RSV in medicine and healthcare are vast. A future research challenge lies in modifying its structure to develop RSV derivatives with superior biological activity and bioavailability. In the coming years, innovative pharmaceutical formulations of RSV, including oral, injectable, and topical preparations, may be developed to enhance its bioavailability and therapeutic efficacy.

Abstract Pseudomonas aeruginosa is an important cause of lower respiratory tract infections, such as ventilator-associated bacterial pneumonia (VABP). Using inhaled antibiotics to treat VABP can achieve high drug concentrations at the infection site while minimizing systemic toxicities. Despite the theoretical advantages, clinical trials have failed to show a benefit for inhaled antibiotic therapy in treating VABP. A potential reason for this discordance is the presence of biofilm-embedded bacteria in lower respiratory tract infections. Drug selection and dosing are often based on data from bacteria grown planktonically. In the present study, an in vitro air-liquid interface pharmacokinetic/pharmacodynamic biofilm model was optimized to evaluate the activity of simulated epithelial lining fluid exposures of inhaled and intravenous doses of polymyxin B and tobramycin against two P. aeruginosa strains. Antibiotic activity was also determined against the P. aeruginosa strains grown planktonically. Our study revealed that inhaled antibiotic exposures were more active than their intravenous counterparts across biofilm and planktonic populations. Inhaled exposures of polymyxin B and tobramycin exhibited comparable activity against planktonic P. aeruginosa. Although inhaled polymyxin B exposures were initially more active against P. aeruginosa biofilms (through 6 h), tobramycin was more active by the end of the experiment (48 h). Together, these data slightly favor the use of inhaled tobramycin for VABP caused by biofilm-forming P. aeruginosa that are not resistant to either antibiotic. The optimized in vitro air-liquid interface pharmacokinetic/pharmacodynamic biofilm model may be beneficial for the development of novel anti-biofilm agents or to optimize antibiotic dosing for infections such as VABP.

BackgroundIn recent years, the incidence of insulin resistance is increasing, and it can cause a variety of Metabolic syndrome. Ginsenosides have been clinically proven to improve fat metabolism and reduce insulin resistance, but their components and mechanism of action are still unclear.ObjectiveGinsenoside, a bioactive compound derived from ginseng, exhibits significant potential in treating obesity, diabetes, and metabolic disorders. Despite evidence supporting its efficacy in ameliorating insulin resistance (IR) in obesity, the specific bioactive components and underlying mechanisms remain obscure. In this study, we endeavored to elucidate the potential molecular targets and pathways influenced by ginsenoside Rh3 (GRh3) to ameliorate IR in liver tissue. We employed a comprehensive approach that integrates system pharmacology and bioinformatics analysis.Materials and methodsOur methodology involved the identification of candidate targets for GRh3 and the profiling of differentially expressed genes (DEGs) related to IR in individuals with insulin resistance. The coalescence of candidate targets and DEGs facilitated the construction of a “GRh3-targets-disease” network for each tissue type, ultimately yielding 38 shared target genes. Subsequently, we conducted pathway enrichment analysis, established protein-protein interaction (PPI) networks, and identified hub targets among the GRh3 targets and IR-related DEGs. Additionally, we conducted animal experiments to corroborate the role of these hub targets in the context of GRh3.ResultsOur investigation identified a total of 38 overlapping targets as potential candidates. Notably, our analysis revealed crucial hub targets such as EGFR, SRC, ESR1, MAPK1, and CASP3, alongside implicated signaling pathways, including those related to insulin resistance, the FoxO signaling pathway, the PPAR signaling pathway, and the IL-17 signaling pathway. This study establishes a robust foundation for the mechanisms underlying GRh3’s efficacy in mitigating IR. Furthermore, these results suggest that GRh3 may serve as a representative compound within the ginsenoside family.ConclusionThis study elucidates the potential molecular targets and associated pathways through which GRh3 ameliorates IR, showcasing its multifaceted nature, spanning multiple targets, pathways, and mechanisms. These findings establish a robust foundation for subsequent experimental inquiries and clinical applications.

Dairy slurry could be a significant source of nitrogen (N) for plants, but mismanagement can lead to atmospheric ammonia losses or nitrate leaching into groundwater. To make the use of dairy slurry efficient and reasonable, the loss of N pollution to the environment should be reduced. We used repacked lysimeters to comprehensively determine ammonia emission and N leaching losses in an alfalfa–soil system. The application of dairy slurry had no significant effect on alfalfa yield at the same rate of N application in comparison to chemical fertilizer, and adding humic acids significantly increased yield by about 12%. However, the application of dairy slurry increased the ammonia emission rate significantly, leading to an increase in the cumulative amount of ammonia emission, while the addition of humic acids reduced the ammonia emissions by 11%. Chemical fertilizer and dairy slurry application significantly increased nitrate leaching compared to the control treatment, while the addition of humic acids can significantly reduce ammonium N leaching. Dairy slurry was proven to be as effective as chemical N fertilizer in achieving the optimum biomass, and adding humic acids can significantly reduce N loss to the atmosphere and groundwater. This study showed the possibility of replacing chemical fertilizer with dairy slurry in alfalfa production and the advantages of humic acids’ addition to alfalfa to maintain production yield and improve environmental friendliness.

Background. Serum uric acid (SUA) and glycosylated hemoglobin (HbA1c) were closely related to the body’s metabolism. This study aimed to investigate the relationship between HbA1c and SUA in adults. Methods. This study selected 7293 participants aged ≥20 from 2011 to 2020 in the National Health and Nutrition Examination Survey (NHANES). The multivariate linear regression model was used to test the association between HbA1c and SUA. Subgroup analysis was performed according to age, gender, race, and body mass index (BMI). This study solved the relationship between HbA1c and SUA by fitting a smooth curve. Finally, the inflection point in the nonlinear relationship was calculated by the recursive algorithm, and the relationship between HbA1c and SUA on both sides of the inflection point was analyzed by the two-segment piecewise linear regression model. Results. All 7293 participants found a negative correlation between HbA1c and SUA by completely adjusting the model (β = −7.93 and 95% CI: −9.49–−6.37). In addition, when this study was stratified by gender, age, race, and BMI status, this negative correlation was still statistically significant. In the subgroup analysis, we found that the relationship between the two had different results due to gender differences. In men, HbA1c had a significant negative correlation with SUA. However, in women, the HbA1c value was positively correlated with SUA before 6.8%, and the HbA1c value was negatively correlated with SUA after 6.8%, which indicates that the relationship between HbA1c and SUA in women has changed in prediabetes and diabetes. Conclusion. This study shows that HbA1c is positively correlated with SUA in American adults before 7%. There is a negative correlation after the HbA1c value of 7%.

Abstract Background Tumor-associated macrophages are considered to be a major contributor affecting the development of tumors. Recently, numerous studies have shown that tumor cells were able to educate their microenvironment by delivering a significant amount of exosomes, however, the mechanism that exosomes from PCa cells work in macrophage polarization remains obscure. Therefore, we sought to determine whether blockade of exosome generation by GW4869, an inhibitor of exosome biogenesis, would impede macrophages from differentiating into M2 cells. Results In this study, we first obtained exosomes from the supernatant media of PCa cells cultured with exosome-free serum using the Magcapture™ Exosome Isolation Kit PS, and then investigated their effects on macrophages. Our data confirmed that exosomes released by prostate cancer cells can induce macrophages to differentiate into M2 cells. Mechanistically speaking, exosomes exert their effects on macrophages through activating the AKT and STAT3 signaling pathways. Importantly, treatment with GW4869 significantly inhibited the release of exosomes from PCa cells, and further impaired M2 differentiation of macrophages and their pro-tumor activity. We also demonstrated that GW4869 was able to inhibit the education of M2 macrophages, and then inhibit the progression of prostate cancer in vivo. Conclusions In brief, our findings indicated that GW4869 impeded the PCa exosome-induced M2 differentiation of macrophages and the progression of prostate cancer, suggesting that GW4869 could play an important role in the treatment of prostate cancer metastasis as an inhibitor of tumor exosome secretion.

Glioma is the most common primary adult brain tumor. Mounting research has illustrated the function of long noncoding RNAs (lncRNAs) in glioma progress, but almost no studies have reported the role of TCL1 upstream neural differentiation-associated RNA (TUNAR) in glioma cells. This study aimed to investigate the function of TUNAR in glioma. The GL15 cell line was used in this study. The interactions between TUNAR and miR-200a, or miR-200a and Rac1 were determined by cotransfection experiments. TUNAR overexpression significantly inhibited glioma malignancy by decreasing cell viability, migration, and invasion and promoting cell apoptosis. TUNAR was confirmed to positively regulate miR-200a, and knockdown of miR-200a reversed the TUNAR-induced inhibitory effects on glioma cells. Further, Rac1 was negatively regulated by miR-200a. Rac1 overexpression abolished miR-200a overexpression-induced inhibition of viability, migration, and invasion, as well as the increase in apoptosis. Rac1 knockdown inhibited glioma by inactivating the Wnt/b-catenin and NF-kB signaling pathways. Our findings suggested that TUNAR played an anticancer role in glioma cells by upregulating miR-200a and inhibiting Rac1, and so might represent a potential therapeutic target for the treatment of human glioma. [ABSTRACT FROM AUTHOR]