Examination of primary aromatic amines content in polylactic acid straws and migration into food simulants using SERS with LC-MS.

Polylactic acid (PLA) straws hold eco-friendly potential; however, residual diisocyanates used to enhance the mechanical strength can generate carcinogenic primary aromatic amines (PAAs), posing health risks. Herein, we present a rapid, comprehensive strategy to detecting PAAs in 18 brands of food-grade PLA straws and assessing their migration into diverse food simulants. Surface-enhanced Raman spectroscopy was conducted to rapidly screen straws for PAAs. Subsequently, qualitative determination of migrating PAAs into various food simulants (4 % acetic acid, 10 % ethanol, 50 % ethanol) occurred at 70 °C for 2 h using liquid chromatography-mass spectrometry. Three PAAs including 4,4'-methylenedianiline, 2,4'-methylenedianiline, and 2,4-diaminotoluene were detected in all straws. Specifically, 2,4-diaminotoluene in 50 % ethanol exceeded specific migration limit of 2 µg/kg, raising safety concerns. Notably, PAAs migration to 10 % and 50 % ethanol surpassed that to 4 % acetic acid within a short 2-hour period. Moreover, PLA straws underwent varying degrees of shape changes before and after migration. Straws with poly(butylene succinate) resisted deformation compared to those without, indicating enhanced heat resistance, while poly(butyleneadipate-co-terephthalate) improved hydrolysis resistance. Importantly, swelling study unveiled swelling effect wasn't the primary factor contributing to the increased PAAs migration in ethanol food simulant, as there was no significant disparity in swelling degrees across different food simulants. FT-IR and DSC analysis revealed higher PAAs content in 50 % ethanol were due to highly concentrated polar ethanol disrupting hydrogen bonds and van der Waal forces holding PLA molecules together. Overall, minimizing contact between PLA straws and alcoholic foods is crucial to avoid potential safety risks posed by PAAs.

NOX4 exacerbates Parkinson's disease pathology by promoting neuronal ferroptosis and neuroinflammation.

JOURNAL/nrgr/04.03/01300535-202507000-00026/figure1/v/2024-09-09T124005Z/r/image-tiff Parkinson's disease is primarily caused by the loss of dopaminergic neurons in the substantia nigra compacta. Ferroptosis, a novel form of regulated cell death characterized by iron accumulation and lipid peroxidation, plays a vital role in the death of dopaminergic neurons. However, the molecular mechanisms underlying ferroptosis in dopaminergic neurons have not yet been completely elucidated. NADPH oxidase 4 is related to oxidative stress, however, whether it regulates dopaminergic neuronal ferroptosis remains unknown. The aim of this study was to determine whether NADPH oxidase 4 is involved in dopaminergic neuronal ferroptosis, and if so, by what mechanism. We found that the transcriptional regulator activating transcription factor 3 increased NADPH oxidase 4 expression in dopaminergic neurons and astrocytes in an 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced Parkinson's disease model. NADPH oxidase 4 inhibition improved the behavioral impairments observed in the Parkinson's disease model animals and reduced the death of dopaminergic neurons. Moreover, NADPH oxidase 4 inhibition reduced lipid peroxidation and iron accumulation in the substantia nigra of the Parkinson's disease model animals. Mechanistically, we found that NADPH oxidase 4 interacted with activated protein kinase C α to prevent ferroptosis of dopaminergic neurons. Furthermore, by lowering the astrocytic lipocalin-2 expression, NADPH oxidase 4 inhibition reduced 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced neuroinflammation. These findings demonstrate that NADPH oxidase 4 promotes ferroptosis of dopaminergic neurons and neuroinflammation, which contribute to dopaminergic neuron death, suggesting that NADPH oxidase 4 is a possible therapeutic target for Parkinson's disease.

Signaling Pathways (TNF-α-NF-κB, TLR2-TLR4 as well as ROS-MDA) and Cardiac Damages during Cardiac Surgeries (Coronary stenting, Permanent Pacemaker Implantations, Radiofrequency Ablations).

INTRODUCTION: The mutual activations of multiple signaling pathways are the key factors in the development and progression of myocardial cell injuries. OBJECTIVE: This research aimed to compare the different degrees of myocardial injury after coronary stenting, permanent pacemaker implantations, or cardiac radiofrequency ablation and to investigate the effects of the mutual activation of TNF-α/NF-κB, TLR2/TLR4, and ROS/MDA signaling pathways on myocardial injury in elderly patients after coronary stents or permanent pacemakers or radiofrequency ablation. METHODS: We determined reactive oxygen species (ROS), malondialdehyde (MDA), toll-like receptor 2 (TLR2), toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), tumor necrosis factor- α (TNF-α) and high-sensitive cardiac troponin T (hs-cTnT) as a marker of myocardial injury in patients. RESULTS: The levels of ROS, MDA, TLR2, TLR4, NF-κB, TNF-α, and hs-cTnT were increased in patients with permanent pacemaker implantations when compared to patients with cardiac radiofrequency ablation (P < 0.01) at 6 months and were further increased in patients with coronary stenting compared to patients with cardiac radiofrequency ablation and permanent pacemaker implantations at 6 months, respectively (P < 0.01). This research confirmed that ROS, MDA, TLR2, TLR4, NF-κB, and TNF-α predicted myocardial injury severity. CONCLUSION: Oxidative stress (ROS/MDA signaling pathway) may be linked to immune response (TLR2/TLR4 signaling pathway) and pro-inflammatory response (TNF-α/NF-κB signaling pathway) in myocardial injury, and ROS/MDA signaling may play a dominant role.

The chemokine receptor type 5 inhibitor maraviroc alleviates sepsis-associated liver injury by regulating MAPK/NF-κB signaling.

Sepsis-related organ damage, as the most intractable problem in intensive care units (ICUs), receives a great deal of attention from healthcare professionals. Sepsis-associated liver injury (SALI) often leads to poor clinical outcomes due to its complex physiological mechanism. In previous studies, chemokine receptor 5 (CCR5) inhibitors were shown to exert unique anti-inflammatory effects. As the therapeutic effect of maraviroc (MVC) on SALI is still unclear, we aimed to explore whether MVC is effective in treating SALI. We established a model of SALI by cecal ligation and puncture (CLP) and intraperitoneally injected 20 mg/kg MVC 2 h after CLP. The results showed that MVC could significantly ameliorate liver injury after CLP. Furthermore, we demonstrated that MVC reduced inflammatory infiltration and apoptosis after SALI. In addition, we found that the function of MVC in reducing inflammation was obtained through the inhibition of the two inflammatory signaling pathways mentioned above. Finally, the JNK agonist AN was chosen for reverse research. As shown by the results, the therapeutic effects of MVC disappeared after AN treatment, indicating that MVC exerted anti-inflammatory and antiapoptotic effects through JNK. Our study revealed that MVC could reduce liver injury after SALI by inhibiting liver inflammation and hepatocyte apoptosis induced by CLP and that MVC exerted diminish inflammatory effects by inhibiting the NF-κB and MAPK signaling pathways.

Hybrid recognition-enabled ratiometric electrochemical sensing of Staphylococcus aureus via in-situ growth of MOF/Ti3C2Tx-MXene and a self-reporting bacterial imprinted polymer.

Rapid and effective analysis of foodborne bacteria is crucial for preventing and controlling bacterial infections. Here, we present the synthesis of a self-reporting molecularly imprinted polymer (MIP) as an inner reference probe (IR), and the in-situ growth of metal-organic frameworks on transition metal carbon nitrides (MOF/Ti3C2TX-MXene) as a signaling nanoprobe (SP). These advancements are then applied in a ratiometric electrochemical bioassay for Staphylococcus aureus (S. aureus) using a hybrid recognition mechanism. When S. aureus is present, the aptamer-integrated MIP (MIP@Apt) efficiently captures it, followed by binding with SP to form a sandwich structure. This leads to decreased current response of IR (IIR) and increased current intensity of SP (Isp), enabling quantification through utilization of the ISP to IIR ratio. The biosensor shows a wide detection range (10-108 CFU mL-1) and low detection limit of 1.2 CFU mL-1. Its feasibility for testing complex samples indicates the potential application in food analysis.

Nurses' preferences for working in Uber-style 'Internet plus' nursing services: A discrete choice experiment.

BACKGROUND: China's 'Internet Plus' nursing services, which are Uber-style home care services with an 'online application, offline service' approach, have been evolving over the past five years. Registered nurses' preference for these Uber-style Internet Plus nursing services are crucial for improving human resource management and service efficiency, yet research in this area remains scarce. OBJECTIVE: This study aimed to explore registered nurses' preferences for Uber-style Internet Plus nursing services and provide optimization recommendations from a supply-side perspective. DESIGN: A cross-sectional study utilising a discrete choice experiment. SETTING(S): Two public tertiary hospitals located in Tianjin, China, which have implemented Internet Plus nursing services. PARTICIPANTS: 211 registered nurses who participated in Internet Plus nursing services. METHODS: The survey was conducted anonymously using an online survey platform. Respondents were presented with choices between two alternatives, based on five key attributes: income, safety and security, patient and family cooperation, commute time, and service type. Mixed logit models estimated the stated preferences for attributes. Relative importance scores, willingness-to-pay estimates, and simulations of service-type uptake rates were calculated. Subgroup analysis and seemingly unrelated regression estimation were performed to examine heterogeneity in preferences. RESULTS: A total of 3202 choice observations were generated. When sorted by the strength of preference, the five attributes related to registered nurses' choice of Uber-style Internet Plus nursing services, measured by their relative importance scores, are as follows: safety and security (30.89 %), income (27.41 %), patient and family cooperation (18.47 %), service type (11.96 %), and commuting time (11.27 %). Elevating safety and security from low to high levels has the same utility as a 31.81 % increase in monthly income, equivalent to 2586.14 yuan. Subgroup analysis showed that senior nurses place more value on safety and security than junior nurses (ß = 1.421 vs.ß = 0.725; P = 0.011), and unmarried nurses had a stronger preference for family and caregiver cooperation (ß = 1.105 vs.ß = 0.314; P = 0.023). CONCLUSIONS: The strength and heterogeneity of registered nurses' preferences should be highlighted in the dispatch algorithms model of Uber-style Internet Plus nursing services, thereby enhancing the efficiency and humanity of Uber-style Internet Plus nursing services. TWEETABLE ABSTRACT: Registered nurses prioritise safety and security, acknowledging heterogeneous preferences in Uber-style Internet Plus nursing services.

Cryptosporidium PI(4)K inhibitor EDI048 is a gut-restricted parasiticidal agent to treat paediatric enteric cryptosporidiosis.

Diarrhoeal disease caused by Cryptosporidium is a major cause of morbidity and mortality in young and malnourished children from low- and middle-income countries, with no vaccine or effective treatment. Here we describe the discovery of EDI048, a Cryptosporidium PI(4)K inhibitor, designed to be active at the infection site in the gastrointestinal tract and undergo rapid metabolism in the liver. By using mutational analysis and crystal structure, we show that EDI048 binds to highly conserved amino acid residues in the ATP-binding site. EDI048 is orally efficacious in an immunocompromised mouse model despite negligible circulating concentrations, thus demonstrating that gastrointestinal exposure is necessary and sufficient for efficacy. In neonatal calves, a clinical model of cryptosporidiosis, EDI048 treatment resulted in rapid resolution of diarrhoea and significant reduction in faecal oocyst shedding. Safety and pharmacological studies demonstrated predictable metabolism and low systemic exposure of EDI048, providing a substantial safety margin required for a paediatric indication. EDI048 is a promising clinical candidate for the treatment of life-threatening paediatric cryptosporidiosis.

Unveiling shared diagnostic biomarkers and molecular mechanisms between T2DM and sepsis: Insights from bioinformatics to experimental assays.

Septic patients with T2DM were prone to prolonged recovery and unfavorable prognoses. Thus, this study aimed to pinpoint potential genes related to sepsis with T2DM and develop a predictive model for the disease. The candidate genes were screened using protein-protein interaction networks (PPI) and machine learning algorithms. The nomogram and receiver operating characteristic curve were developed to assess the diagnostic efficiency of the biomarkers. The relationship between sepsis and immune cells was analyzed using the CIBERSORT algorithm. The biomarkers were validated by qPCR and western blotting in basic experiments, and differences in organ damage in mice were studied. Three genes (MMP8, CD177, and S100A12) were identified using PPI and machine learning algorithms, demonstrating strong predictive capabilities. These biomarkers presented significant differences in gene expression patterns between diseased and healthy conditions. Additionally, the expression levels of biomarkers in mouse models and blood samples were consistent with the findings of the bioinformatics analysis. The study elucidated the common molecular mechanisms associated with the pathogenesis of T2DM and sepsis and developed a gene signature-based prediction model for sepsis. These findings provide new targets for the diagnosis and intervention of sepsis complicated with T2DM.

Exogenous and endogenous formaldehyde-induced DNA damage in the aging brain: mechanisms and implications for brain diseases.

Exogenous gaseous formaldehyde (FA) is recognized as a significant indoor air pollutant due to its chemical reactivity and documented mutagenic and carcinogenic properties, particularly in its capacity to damage DNA and impact human health. Despite increasing attention on the adverse effects of exogenous FA on human health, the potential detrimental effects of endogenous FA in the brain have been largely neglected in current research. Endogenous FA have been observed to accumulate in the aging brain due to dysregulation in the expression and activity of enzymes involved in FA metabolism. Surprisingly, excessive FA have been implicated in the development of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and brain cancers. Notably, FA has the ability to not only initiate DNA double strand breaks but also induce the formation of crosslinks of DNA-DNA, DNA-RNA, and DNA-protein, which further exacerbate the progression of these brain diseases. However, recent research has identified that FA-resistant gene exonuclease-1 (EXO1) and FA scavengers can potentially mitigate FA toxicity, offering a promising strategy for mitigating or repairing FA-induced DNA damage. The present review offers novel insights into the impact of FA metabolism on brain ageing and the contribution of FA-damaged DNA to the progression of neurological disorders.

Hyaluronic acid-zein shell-core biopolymer nanoparticles enhance hepatocellular carcinoma therapy of celastrol via CD44-mediated cellular uptake.

Low concentrations or limited residence times in tumor tissues, making celastrol (Cel) difficult to exert significant therapeutic effects. Thus, we developed Zein/hyaluronic acid core-shell nanoparticles (Cel/Zein@HA NPs) for active targeted delivery of Cel via CD44 receptor over-expression on cancer cells, which may strengthen the therapeutic efficacy of Cel and improve delivery targeting. Cel-loaded Zein nanoparticles (core), are elegantly enveloped by a hydrophilic HA coating that forms the shell, resulting in significantly improved encapsulation efficiency and ensured good stability. The cellular uptake of Cel/Zein@HA NPs in HepG2 cells was 1.57-fold higher than nontargeting Cel/Zein NPs. Near-infrared fluorescence imaging confirmed the accumulation of Cel/Zein@HA NPs in H22 liver cancer tumors in mice, resulting in effective antitumor effects and good biosafety. Besides, in vitro and in vivo experiments showed that compared with Cel/Zein NPs, Cel/Zein@HA NPs had more efficient inhibitory effect on tumor proliferation and lower systemic toxicity. Further studies revealed that Cel/Zein@HA NPs induced apoptosis in hepatocellular carcinoma cells by modulating Bax and Bcl-2 expression, while also inhibiting tumor angiogenesis by decreasing CD31 and VEGF levels. Overall, this study presents a promising strategy for enhancing targeted liver cancer therapy through the utilization of biopolymer nanoparticle-based nano-pharmaceuticals that facilitate CD44-mediated cellular uptake.

Trifluoperazine effect on human sperm: the accumulation of reactive oxygen species and the decrease in the mitochondrial membrane potential.

A strong link between antipsychotic drug use and reduced human sperm quality has been reported. Trifluoperazine (TFP), a commonly used antipsychotic, is now being explored for anticancer applications. Although there are hints that TFP might affect the male reproductive system, its impact on human sperm quality remains uncertain. Using a human sperm and TFP in vitro coculture system, we examined the effect of TFP (12.5, 25, 50 and 100µM) on human sperm function and physiological parameters. The results showed that 50µM and 100µM TFP induced the accumulation of reactive oxygen species (ROS) and a decrease in the mitochondrial membrane potential (MMP) of human sperm, leading to decreased sperm viability, while 25µM TFP inhibited only the penetration ability, total sperm motility, and progressive motility. Although 12.5µM and 25µM TFP increased [Ca2+]i in human sperm, they did not affect capacitation or the acrosome reaction. These results may be explained by the observation that 12.5µM and 25µM TFP did not increase tyrosine phosphorylation in human sperm, although TFP increased [Ca2+]i in a time-course traces similar to that of progesterone. Our results indicated that TFP could cause male reproductive toxicity by inducing the accumulation of ROS and a decrease in the MMP in human sperm.

Ion-Engineered Clay Nanozyme via Tumor Microenvironment Remodeling for Enhanced Tumor Therapy.

Metal ions show tremendous promise for tumor therapy due to their critical roles in many important catalytic circulations and immune processes. However, the valence state variability and systemic side-effects of metal ions cause ineffective ion enrichment in tumor cells, which limit their further application. Here, a Mn3+ ion delivery system (Mn-HNT) is constructed based on halloysite nanotubes (HNT) via an ion-engineered strategy. Due to the stabilizing effect of HNT on Mn3+ ions, Mn-HNT not only maintained the valence state of Mn3+ ions, but also presented strong catalase (CAT)- and glutathione oxidase (GSHOx)-like catalytic activity to catalyze O2 generation and GSH consumption to relieve the inhibition of tumor microenvironment on photodynamic therapy (PDT). After further coordination with the photosensitizer porphyrin (TCPP), obtained TCPP-Mn-HNT not only inherited the catalytic properties of Mn-HNT to produce oxygen and consume GSH, but acted as photosensitizer for ROS accumulation to effectively destroy tumor cells. Moreover, TCPP-Mn-HNT can promote the maturation of dendritic cells (≈2.8 times), and present the tumor antigen triggered by PDT to T cells to strengthen high-efficient tumor therapy. The study provides new opportunities for designing metal ion delivery system with versatile biofunctions and offers a paradigm of synergistic metal-ion-mediated tumor therapy.

Exploring the Efficacy of Hyperthermic Intraperitoneal Perfusion Chemotherapy in Gastric Cancer: Meta-analysis Based on Randomized Controlled Trials.

PURPOSE: Based on randomized clinical trials, this meta-analysis evaluated the efficacy and safety of intent-to-cure or prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of gastric cancer. METHODS: PubMed, Cochrane Library, Medline, and Embase databases were all systemically searched from 2004 to 2023. The quality of the study was assessed by using the Cochrane risk of bias method. The certainty of the evidence was determined by using the GRADE evaluation. RESULTS: In this study, 12 articles with a total of 1181 patients were analyzed based on the inclusion criteria. The findings revealed that HIPEC had a higher survival rate (risk ratio [RR] 0.60; 95% confidence interval [CI] [0.43, 0.86], P = 0.005, RR 0.82; 95% CI [0.70, 0.97], P = 0.02, RR 0.83; 95% CI [0.71, 0.96], P < 0.01, and RR 0.63 [0.54, 0.73], P < 0.00001) after 1, 2, 3, and 5 years compared with the control group. The RR was statistically significant for 1, 2, 3, and 5 years. Furthermore, the observed overall recurrence rate for the HIPEC group was lower than control group and statistically significant (RR 0.59; 95% CI [0.50, 0.68], P < 0.0001). Higher disease-free survival rate (RR 1.42; 95% CI [1.07, 1.89], P < 0.01) was observed in the HIPEC group and statistically significant. CONCLUSIONS: Gastric cancer patients treated with HIPEC have shown promising outcomes with regard to survival, recurrence, disease-free survival, and adverse reactions. However, multicenter trials with larger sample sizes consisting of different ethnicities is suggested.

Bioorthogonal chemistry-based prodrug strategies for enhanced biosafety in tumor treatments: current progress and challenges.

Cancer is a significant global health challenge, and while chemotherapy remains a widely used treatment, its non-specific toxicity and broad distribution can lead to systemic side effects and limit its effectiveness against tumors. Therefore, the development of safer chemotherapy alternatives is crucial. Prodrugs hold great promise, as they remain inactive until they reach the cancer site, where they are selectively activated by enzymes or specific factors, thereby reducing side effects and improving targeting. However, subtle differences in the microenvironments between tumors and normal tissue may still result in unintended cytotoxicity. Bioorthogonal reactions, known for their selectivity and precision without interfering with natural biochemical processes, are gaining attention. When combined with prodrug strategies, these reactions offer the potential to create highly effective chemotherapy drugs. This review examines the safety and efficacy of prodrug strategies utilizing various bioorthogonal reactions in cancer treatment.

Vitrectomy Combined with Repeated Intravitreal Injection of Ceftazidime for the Treatment of Brucellosis Endophthalmitis: A Case Report and Literature Review.

PURPOSE: To present a treatment regimen for Brucellosis endophthalmitis that resulted in a good visual outcome. Additionally, we conducted a literature review on the treatment and visual prognosis of related cases. CASE PRESENTATION: A 49-year-old woman with the chief complaint of decreased vision and redness in the right eye was initially diagnosed with noninfectious uveitis and prescribed high-dose steroids which led to transient improvement followed by a decline in vision. An infectious cause was suspected. Metagenomic next-generation sequencing of vitreous fluid and serological testing confirmed Brucella melitensis infection. The patient underwent vitrectomy combined with six intravitreal injections of ceftazidime in the right eye in addition to systemic antibiotic treatment. The intraocular inflammation was completely resolved, and the visual acuity recovered to 20/25, which is the best-documented recovery in Brucella endophthalmitis cases, as revealed by the literature review. CONCLUSION: Vitrectomy combined with repeated intravitreal injections of ceftazidime can enhance the treatment for brucellosis endophthalmitis and achieve a better visual prognosis.

Lower serum LH level was related to poor embryo quality and adverse pregnancy outcomes in fixed GnRH antagonist protocol with estradiol pretreatment.

OBJECTIVE: To disclose the relationships between serum LH and reproductive outcomes in Gonadotropin-releasing hormone (GnRH) antagonist protocol pretreated with luteal estradiol. METHODS: 371 patients, pretreated with estradiol, followed the GnRH antagonist protocol. They were divided into four groups based on the quartiles of serum LH levels on the day of gonadotropin (Gn) initiation(LHGI) and trigger (LHtrigger). Data on various pregnancy outcomes were collected. RESULTS: As serum LHGI increased, anti-Müllerian hormone (AMH) level, antral follicle count (AFC), LHtrigger, estradiol (E2) and P on the trigger day, E2/oocytes, and oocyte numbers increased and peaked in Q4, while Gn dose decreased. Good-quality embryo and blast formation rates increased and peaked in Q3. LHGI <3.93 mIU/ml impaired ongoing pregnancy rate and LBR. After adjusting for AMH and AFC, the impacts were not significant. As LHtrigger increased, E2/oocytes and good-quality embryo rate increased and peaked in T4 and implantation rate increased and peaked in T3. LHtrigger <1.49 mIU/ml independently influenced clinical pregnancy rate (CPR) after adjusting for AMH and AFC. LHGI was positively related to AMH, AFC, LHtrigger, blast formation rate and negatively related to BMI, age and Gn dose. LHtrigger was positively related to E2/oocytes and good quality embryo rate. CONCLUSIONS: Lower serum LH represents as a potential indicator for embryo quality and reproductive outcomes in GnRH antagonist fixed protocol pretreated with estradiol. Early identification of excessive suppression of LH levels will benefit individuals with normal ovarian reserve more.

Total Synthesis of Rhizopodin Enabled by a Late-Stage Oxazole Ring Formation Strategy.

Actin stabilizers that are capable of interfering with actin cytoskeleton dynamics play an important role in chemical biology. Rhizopodin, a novel actin stabilizer, affects the actin cytoskeleton at nanomolar concentrations and exhibits potent antiproliferative activities against a range of tumor cell lines with IC50 values in the low nanomolar range. Herein, we report the total synthesis of rhizopodin based on a late-stage oxazole ring formation strategy, whose success demonstrates the feasibility of late-stage oxazole ring formation in the synthesis of complex oxazole containing natural products. Other features of the synthesis include a Nagao aldol reaction, a Suzuki coupling, a Yamaguchi esterification, a modified Robinson-Gabriel synthesis of the oxazoles, and a bidirectional Ba(OH)2-mediated Horner-Wadsworth-Emmons (HWE) reaction.

Associations of Dietary Magnesium Intake with All-Cause and Cause-Specific Mortality Among Individuals with Gout and Hyperuricemia.

We aimed to evaluate the relationship of dietary magnesium intake with all-cause and cause-specific mortality among patients with gout and hyperuricemia (HUA). We analyzed data of 1171 gout patients and 6707 HUA patients from the National Health and Nutrition Examination Survey (NHANES) 2007-2018 and 2001-2018, respectively. Dietary intake data were obtained from 24-h dietary recall interviews. Mortality status was determined using the NHANES public-use linked mortality fill. We used Cox regression model and restricted cubic spline analysis to probe the association of dietary magnesium intake and mortality among gout and HUA patients. During 7081 person-years of follow-up, 257 deaths were documented in gout patients, among which 74 died from cardiovascular disease (CVD) and 48 died from cancer. For HUA patients followed up for 58,216 person-years, 1315 all-cause deaths occurred, including 411 CVD deaths and 224 cancer deaths. After multifactorial adjustments, higher dietary magnesium intake was associated with lower risk of all-cause mortality. Nonlinear negative associations were found between dietary magnesium intake and CVD mortality among gout and HUA patients, with inflection points of 152.5 mg/day and 303 mg/day, respectively, and cancer mortality among HUA patients, with the inflection point of 232 mg/day. The results were robust in subgroup and sensitivity analyses. High dietary magnesium intake is linearly related to all-cause mortality, and nonlinearly associated with cause-specific mortality among gout and HUA patients.

Sex differences in the development of experimental diabetic retinopathy.

This study aimed to characterize the role of female sex in the pathogenesis of diabetic retinopathy. In the retinae of female Ins2Akita-diabetic mice (F-IA), ovariectomized female Ins2Akita-diabetic mice (F-IA/OVX), male Ins2Akita-diabetic mice (M-IA), and female STZ-diabetic mice (F-STZ), the formation of reactive metabolites and post-translational modifications, damage to the neurovascular unit, and expression of cellular stress response genes were analyzed. Compared to the male diabetic retina, the concentrations of the glycation adduct fructosyl-lysine, the Maillard product 3-deoxyglucosone, and the reactive metabolite methylglyoxal were significantly reduced in females. In females, there was also less evidence of diabetic damage to the neurovascular unit, as shown by decreased pericyte loss and reduced microglial activation. In the male diabetic retina, the expression of several members of the crystallin gene family (Cryab, Cryaa, Crybb2, Crybb1, and Cryba4) was increased. Clinical data from type 1 diabetic females showed that premenopausal women had a significantly lower prevalence of diabetic retinopathy compared to postmenopausal women stratified for disease duration and glycemic control. These data emphasize the importance of estradiol in protecting the diabetic retina and highlight the pathogenic relevance of sex in diabetic retinopathy.