A Hybrid Redox-Mediated Zinc-Air Fuel Cell for Scalable and Sustained Power Generation.

Zinc-air batteries (ZABs) have attracted considerable attention for their high energy density, safety, low noise, and eco-friendliness. However, the capacity of mechanically rechargeable ZABs was limited by the cumbersome procedure for replacing the zinc anode, while electrically rechargeable ZABs suffer from issues including low depth of discharge, zinc dendrite and dead zinc formation, and sluggish oxygen evolution reaction, etc. To address these issues, we report a hybrid redox-mediated zinc-air fuel cell (HRM-ZAFC) utilizing 7,8-dihydroxyphenazine-2-sulfonic acid (DHPS) as the anolyte redox mediator, which shifts the zinc oxidation reaction from the electrode surface to a separate fuel tank. This approach decouples fuel feeding and electricity generation, providing greater operation flexibility and scalability for large-scale power generation applications. The DHPS-mediated ZAFC exhibited a superior peak power density of 0.51 W/cm2 and a continuous discharge capacity of 48.82 Ah with ZnO as the discharge product in the tank, highlighting its potential for power generation.

Association between vitamin D, depression, and sleep health in the National Health and Nutrition Examination Surveys: a mediation analysis.

OBJECTIVE: This study aimed to assess the association between vitamin D and sleep health and to investigate whether depression could mediate this relationship. METHODS: A cross-sectional analysis was performed using the 2005-2014 US National Health and Nutrition Examination Survey (NHANES) data. The logistic regression models were conducted to evaluate association of serum vitamin D concentrations with sleep health and depression. Mediation analyses were conducted to investigate the mediated effects of depression on the association of vitamin D with sleep health. RESULTS: In multivariate logistic models, vitamin D was found to be negatively associated with an increased risk of poor sleep health, with an odds ratio (OR) of vitamin D deficiency versus sufficiency was 1.256 (95% CI = 1.084-1.455). Additionally, univariate logistic models showed that vitamin D was also negatively associated with depression risk (vitamin D deficiency vs. sufficiency: OR = 1.699, 95% CI = (1.373-2.103). Further mediation analyses showed that the association of vitamin D with sleep health was mediated by depression, with the mediating effects of depression accounted for 44.56% of the total effects. CONCLUSION: Vitamin D affects sleep health directly and indirectly through depression. The results suggest that interventions increasing intake of vitamin D should be prioritized to promote sleep health of persons with or at risk of depression.

Characterization of non-cardiac arrest PulsePoint activations in public and private settings.

BACKGROUND: Geospatial smartphone application alert systems are used in some communities to crowdsource community response for out-of-hospital cardiac arrest (OHCA). Although the clinical focus of this strategy is OHCA, dispatch identification of OHCA is imperfect so that activation may occur for the non-arrest patient. The frequency and clinical profile of such non-arrest patients has not been well-investigated. METHODS: We undertook a prospective 3-year cohort investigation of patients for whom a smartphone geospatial application was activated for suspected OHCA in four United States communities (total population ~1 million). The current investigation evaluates those patients with an activation for suspected OHCA who did not experience cardiac arrest. The volunteer response cohort included off-duty, volunteer public safety personnel (verified responders) notified regardless of location (public or private) and laypersons notified to public locations. The study linked the smartphone application information with the EMS records to report the frequency, condition type, and EMS treatment for these non-arrest patients. RESULTS: Of 1779 calls where volunteers were activated, 756 had suffered OHCA, resulting in 1023 non-arrest patients for study evaluation. The most common EMS assessments were syncope (15.9%, n=163), altered mental status (15.5%, n=159), seizure (14.3%, n=146), overdose (13.0%, n=133), and choking (10.5%, n=107). The assessment distribution was similar for private and public locations. Overall, the most common EMS interventions included placement of an intravenous line (43.1%, n=441), 12-Lead ECG(27.9%, n=285), naloxone treatment (9.8%, n=100), airway or ventilation assistance (8.7%, n=89), and oxygen administration (6.6%, n=68). CONCLUSIONS: More than half of patients activated for suspected OHCA had conditions other than cardiac arrest. A subset of these conditions may benefit from earlier care that could be provided by both layperson and public safety volunteers if they were appropriately trained and equipped.

Improving Mitochondrial Function in Skeletal Muscle Contributes to the Amelioration of Insulin Resistance by Nicotinamide Riboside.

High-fat diet (HFD)-induced insulin resistance (IR) in skeletal muscle is often accompanied by mitochondrial dysfunction and oxidative stress. Boosting nicotinamide adenine dinucleotide (NAD) using nicotinamide riboside (NR) can effectively decrease oxidative stress and increase mitochondrial function. However, whether NR can ameliorate IR in skeletal muscle is still inconclusive. We fed male C57BL/6J mice with an HFD (60% fat) ± 400 mg/kg·bw NR for 24 weeks. C2C12 myotube cells were treated with 0.25 mM palmitic acid (PA) ± 0.5 mM NR for 24 h. Indicators for IR and mitochondrial dysfunction were analyzed. NR treatment alleviated IR in HFD-fed mice with regard to improved glucose tolerance and a remarkable decrease in the levels of fasting blood glucose, fasting insulin and HOMA-IR index. NR-treated HFD-fed mice also showed improved metabolic status regarding a significant reduction in body weight and lipid contents in serum and the liver. NR activated AMPK in the skeletal muscle of HFD-fed mice and PA-treated C2C12 myotube cells and upregulated the expression of mitochondria-related transcriptional factors and coactivators, thereby improving mitochondrial function and alleviating oxidative stress. Upon inhibiting AMPK using Compound C, NR lost its ability in enhancing mitochondrial function and protection against IR induced by PA. In summary, improving mitochondrial function through the activation of AMPK pathway in skeletal muscle may play an important role in the amelioration of IR using NR.

High-Power Near-Neutral Aqueous All Organic Redox Flow Battery Enabled with a Pair of Anionic Redox Species.

Aqueous organic redox flow batteries (AORFBs) are regarded as a promising alternative for low-cost and durable grid-scale energy storage. However, the narrow potential gap, chemical lability and membrane fouling in most AORFBs constitute formidable roadblocks for practical applications. Herein, a pair of anionic organic molecules, namely (PPBPy)Br2 and PSS-TEMPO, are proposed. The (PPBPy)Br2 in anolyte reveals remarkable electrochemical stability without degradation after 1000 cycles, while PSS-TEMPO in catholyte presents a capacity decay rate as low as 0.012 %/cycle. At near-neutral conditions, the (PPBPy)Br2 /PSS-TEMPO flow cell exhibits a high voltage of 1.61 V, extremely low permeability across cation-exchange membrane and thus excellent cycling stability. Notably, a highest peak power density of 509 mW cm-2 has been achieved among reported all-organic aqueous RFBs. The molecular engineering strategies demonstrated here could provide a credible example of high-performance AORFBs.

Decoupled Redox Catalytic Hydrogen Production with a Robust Electrolyte-Borne Electron and Proton Carrier.

Electrolytic water splitting is an effective approach for H2 mass production. A conventional water electrolyzer concurrently generates H2 and O2 in neighboring electrode compartments separated by a membrane, which brings about compromised purity, energy efficiency, and system durability. On the basis of distinct redox electrochemistry, here, we report a system that enables the decoupling of both the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) from the electrodes to two spatially separated catalyst bed reactors in alkaline solutions. Through a pair of close-loop electrochemical-chemical cycles, the system operates upon 7,8-dihydroxy-2-phenazinesulfonic acid (DHPS) and ferricyanide-mediated HER and OER, respectively, on Pt/Ni(OH)2 and NiFe(OH)2 catalysts. Near unity faradaic efficiency and sustained production of hydrogen has been demonstrated at a current density up to 100 mA/cm2. The superior reaction kinetics, particularly the HER reaction mechanism of DHPS as a robust electrolyte-borne electron and proton carriers, were scrutinized both computationally and experimentally. We anticipate the system demonstrated here would provide an intriguing alternative to the conventional water electrolytic hydrogen production.

The anti-cancer compound Schweinfurthin A targets Osh2 and disrupts lipid metabolism in the yeast model.

Schweinfurthin A (Sch A) is a natural product with a selective and strong anti-cancer effect. Although it is known to target oxysterol binding proteins, the detailed mode of action is not well understood. Here, we provide strong evidence that yeast cells can be used as a eukaryotic model system to decipher the molecular modes of Sch A. We show that Sch A (100 µM) targets Osh2 (a yeast oxysterol binding protein homolog) genetically and taking advantage of computational chemistry indicate that the tetrahydro-2H-xanthene portion of Sch A forms H-bonds with residues Ser105, Val113, and Lys201, while its isoprenoid side chain is placed in a hydrophobic pocket lined by the side chains of Leu41, Leu45, Leu58, Met56, and Phe174 in Osh2. This model suggests that Sch A occupies the same binding pocket in Osh2 which is occupied by its natural substrate, ergosterol. Osh proteins transport sterol and PI(4)P in a cyclic manner between two membranes. Therefore, we suggest that Sch A interferes with this function of Osh2. In support of this hypothesis, we show that Sch A toxicity rate changes upon manipulating the enzymes that modify the levels of sterol and PI(4)P. This approach also informs how Sch A exerts its toxic effect in yeast cells. These enzymes include Coq1, Sac1, Plc1, Stt4, Pik1, and Mss4. We demonstrate that Coq1 an enzyme required for coenzyme Q synthesis (also involved in sterol metabolism indirectly), Sac1, and Stt4 the enzymes governing PI(4)P level modify Sch A toxicity and finally propose Sch A disrupts sterol/PI(4)P exchange between membranes by occupying the sterol/PI(4)P binding pocket in Osh2.

Design, synthesis, and fungicidal evaluation of novel oxysterol binding protein inhibitors for combatting resistance associated with oxathiapiprolin.

Oxathiapiprolin, the first successful oxysterol binding protein (OSBP) inhibitor for oomycete control, is regarded as an important milestone in the history of fungicide discovery. However, its interaction with OSBP remain unclear. Moreover, some plant pathogenic oomycetes have developed medium to high resistance to oxathiapiprolin. In this paper, the three-dimensional (3D) structure of OSBP from Phytophthora capsici (pcOSBP) was built, and its interaction with oxathiapiprolin was systematically investigated by integrating molecular docking, molecular dynamics simulations, and molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) calculations. The computational results showed that oxathiapiprolin bound to pcOSBP forms H-bonds with Leu73, Lys74, Ser69, and water molecules. Then, based on its interaction with pcOSBP, oxathiapiprolin was structurally modified to discover new analogs with high fungicidal activity and a low risk of resistance. Fortunately, compound 1e was successfully designed and synthesized as the most potent candidate, and it showed a much lower resistance risk (RF < 1) against LP3-M and LP3-H in P. capsici. The present work indicated that the piperidinyl-thiazole-isoxazoline moiety is useful for further optimization. Furthermore, compound 1e could be used as a lead compound for the discovery of new OSBP inhibitors.

MX-Chain Compounds with ReO4 Counterions: Exploration of the Robin-Day Class I-II Boundary.

MX chains have been widely studied as a 1D mixed-valence system. Although there have been a large number of studies on the boundary between class II and III materials of the Robin-Day classification, there are few studies of compounds at the boundary between classes I and II. In this study, we synthesized a series of Pt- and Pd- MX-chain compounds with perrhenate counterions, [M(en)2][M(en)2X2](ReO4)4 (X = Br for M = Pd and X = Cl, Br, and I for M = Pt). All compounds were isostructural, and the metal-metal distances within the chain exceed 6 Å, which is the longest among MX-chain compounds thus far reported. For [Pt(en)2][Pt(en)2Cl2](ReO4)4 (PtCl), an intervalence charge transfer (IVCT) transition was observed in the UV region at 335 nm (3.7 eV), which is the shortest wavelength for the MX-chain compounds thus far reported, indicating that PtCl is the closest to the Robin-Day class I limit.

The role of Cyclin Dependent Kinase Inhibitor 3 (CDKN3) in promoting human tumors: Literature review and pan-cancer analysis.

Background: Although many experiments and clinical studies have proved the link between the expression of CDKN3 and human tumors, we have not been able to identify any bioinformatics study in which the extensive tumor-promoting effect of CDKN3 was systematically analyzed. Objective: Explore the extensive tumor-promoting effects of CDKN3 and review the research progress of CDKN3 in cancer. Methods: We systematically reviewed the literature on CDKN3 and tumors. We explored the potential tumor-promoting effects of CDKN3 on different tumors in the TCGA database and the GTEx database using multiple platforms and websites. We studied the expression level of CDKN3, survival, prognosis, diagnosis, genetic variation, immune infiltration, and enrichment analysis using databases such as TIMER 2.0, GEPIA2, cBioPortal, and STRING. Results: We found that CDKN3 is highly expressed in most tumors. The expression of CDKN3 is closely related to the prognosis of some tumors. And CDKN3 may have diagnostic value. The conclusion of our literature review is roughly the same, but there are differences, which are worthy of further study. Moreover, CDKN3 may be related to immune cell infiltration in tumor tissues. The genetic alteration of LUAD, STAD, SARC, PCPG, and ESCA with "Amplification" as the main type. In addition, through enrichment analysis, we found that CDKN3 affects tumors mainly through the control of the cell cycle and mitosis. Conclusion: CDKN3 is highly expressed in most tumor tissues and has a statistical correlation with survival prognosis. It has extensive tumor-promoting effects that may be related to mechanisms such as immune infiltration.

The diagnostic accuracy of a shock advisory algorithm in automated external defibrillators in the presence of real-world artifacts.

BACKGROUND: The current standards for shock advisory algorithms in AEDs require performance testing on artifact-free ECGs. However, AED analysis in the real world is more challenging due to potential artifacts from various sources (e.g., patient handling, and electromagnetic interference). This retrospective data analysis reports the real-world performance and behavior of a shock advisory algorithm used in three AED models with the presence of artifacts. METHODS: ECG rhythm analyses recorded during the use of three AED models (HS1, FRx and FR3) were reviewed. The shock recommendations made in the AEDs were compared to the expert annotations of reviewers. The effects of real-world artifacts and the handling by the algorithm were analyzed. RESULTS: Among the 3,941 analyses, 619 were annotated as shockable rhythms, and 2,912 were non-shockable. The overall sensitivity and specificity were 97.1% (601/619), and 99.9% (2,908/2,912), respectively. Artifacts were detected by the algorithm in 23.3% (918/3,941) of the analysis periods. The algorithm performance for the analysis periods with artifacts detected was 95.2% (80/84) for sensitivity and 100.0% (687/687) for specificity. In the remaining analysis periods with no artifacts detected, the sensitivity was 97.4% (521/535), and specificity was 99.8% (2,221/2,225). CONCLUSIONS: The performance of this shock advisory algorithm during real-world resuscitations with or without artifacts, exceeded AHA recommendations and the requirements in international standards. The high sensitivity and specificity demonstrate the effectiveness and safety of this algorithm in all three AED models.

Tangshen formula targets the gut microbiota to treat non-alcoholic fatty liver disease in HFD mice: A 16S rRNA and non-targeted metabolomics analyses.

BACKGROUND: Tangshen formula (TSF) has an ameliorative effect on hepatic lipid metabolism in non-alcoholic fatty liver disease (NAFLD), but the role played by the gut microbiota in this process is unknown. METHOD: We conducted three batches of experiments to explore the role played by the gut microbiota: TSF administration, antibiotic treatment, and fecal microbial transplantation. NAFLD mice were induced with a high-fat diet to investigate the ameliorative effects of TSF on NAFLD features and intestinal barrier function. 16S rRNA sequencing and serum untargeted metabolomics were performed to further investigate the modulatory effects of TSF on the gut microbiota and metabolic dysregulation in the body. RESULTS: TSF ameliorated insulin resistance, hypercholesterolemia, lipid metabolism disorders, inflammation, and impairment of intestinal barrier function. 16S rRNA sequencing analysis revealed that TSF regulated the composition of the gut microbiota and increased the abundance of beneficial bacteria. Antibiotic treatment and fecal microbiota transplantation confirmed the importance of the gut microbiota in the treatment of NAFLD with TSF. Subsequently, untargeted metabolomics identified 172 differential metabolites due to the treatment of TSF. Functional predictions suggest that metabolisms of choline, glycerophospholipid, linoleic acid, alpha-linolenic acid, and arachidonic acid are the key metabolic pathways by which TSF ameliorates NAFLD and this may be influenced by the gut microbiota. CONCLUSION: TSF treats the NAFLD phenotype by remodeling the gut microbiota and improving metabolic profile, suggesting that TSF is a functional gut microbial and metabolic modulator for the treatment of NAFLD.

Inhibition of ethanol-induced eNAMPT secretion attenuates liver ferroptosis through BAT-Liver communication.

BACKGROUND & AIMS: Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) has long been recognized as an adipokine. However, the exact role of eNAMPT in alcoholic liver disease (ALD) and its relevance to brown adipose tissue (BAT) remain largely unknown. This study aimed to evaluate the impact of eNAMPT on liver function and the underlying mechanisms involved in BAT-Liver communication. METHODS: Serum eNAMPT levels were detected in the serum of both ALD patients and mice. Chronic and binge ethanol feeding was used to induce alcoholic liver injury in mice. An eNAMPT antibody, a coculture model of brown adipocytes and hepatocytes, and BAT-specific Nampt knockdown mice were used to investigate the role of eNAMPT in ALD. RESULTS: Serum eNAMPT levels are elevated in ALD patients and are significantly positively correlated with the liver injury index. In ALD mice, neutralizing eNAMPT reduced the elevated levels of circulating eNAMPT induced by ethanol and attenuated liver injury. In vitro experiments revealed that eNAMPT induced hepatocyte ferroptosis through the TLR4-dependent mitochondrial ROS-induced ferritinophagy pathway. Furthermore, ethanol stimulated eNAMPT secretion from brown adipocytes but not from other adipocytes. In the coculture model, ethanol-induced release of eNAMPT from brown adipocytes promoted hepatocyte ferroptosis. In BAT-specific Nampt-knockdown mice, ethanol-induced eNAMPT secretion was significantly reduced, and alcoholic liver injury were attenuated. These effects can be reversed by intraperitoneal injection of eNAMPT. CONCLUSION: Inhibition of ethanol-induced eNAMPT secretion from BAT attenuates liver injury and ferroptosis. Our study reveals a previously uncharacterized critical role of eNAMPT-mediated BAT-Liver communication in ALD and highlights its potential as a therapeutic target.

Does dexmedetomidine reduce the risk of acute kidney injury after cardiac surgery? A meta-analysis of randomized controlled trials.

BACKGROUND: Acute Kidney Injury (AKI) is a common complication after cardiac surgery and has been associated with poor outcomes. Dexmedetomidine (DEX) has been shown to confer direct renoprotection based on some animal and clinical studies, but data from other trials came to the opposite conclusion following cardiac surgery. This meta-analysis was conducted to evaluate the effects of perioperative DEX administration on the occurrence of AKI and the outcomes after cardiac surgery. METHODS: We searched databases including EMBASE, PubMed, and Cochrane CENTRAL for Randomized Controlled Trials (RCTs) focused on DEX for AKI in adult patients after cardiac surgery. The primary outcome was incidence of AKI. Secondary outcomes were Mechanical Ventilation (MV) duration, Intensive Care Unit (ICU) Length Of Stay (LOS), hospital LOS and mortality. RESULTS: Fifteen trials enrolling 2907 study patients were collected in the meta-analyses. Compared with controls, DEX reduced the incidence of postoperative AKI (Odds Ratio [OR = 0.66]; 95% Confidence Interval [95% CI 0.48-0.91]; p = 0.01), and there was no significant difference between groups in postoperative mortality (OR = 0.63; 95% CI 0.32-1.26; p = 0.19), MV duration (Weighted Mean Difference [WMD = -0.44]; 95% CI -1.50-0.63; p = 0.42), ICU LOS (WMD = -1.19; 95% CI -2.89-0.51; p = 0.17), and hospital LOS (WMD = -0.31; 95% CI -0.76-0.15; p = 0.19). CONCLUSIONS: Perioperative DEX reduced the incidence of postoperative AKI in adult patients undergoing cardiac surgery. No significant decrease existed in mortality, MV duration, ICU LOS and hospital LOS owing to DEX administration.

Association between C-reactive protein-albumin ratio and overall survival in Parkinson's disease using publicly available data: A retrospective cohort study.

Background: At present, many studies have confirmed that inflammation plays a central role in Parkinson's disease (PD). The inflammatory index is related to the prognosis of the disease, but a single inflammatory index has some limitations. The C-reactive protein-albumin ratio (CAR) is a better marker of inflammation or nutritional status than C-reactive protein (CRP) or albumin (Alb), but there is limited study on the association between CAR and the overall survival (OS) of PD. Object: To study the association between CAR and OS in PD patients. Methods: All of these data were obtained from the Dryad Digital Repository, based on which we conducted a secondary analysis. The study was conducted by the Department of Neurology, the National Regional Center for Neurological Disorders, and the National Hospital of Utano study between March 2004 to November 2007. The final analytic sample included 235 PD patients with the outcome of survival or all-cause death from the study registration to the endpoint. In this study, univariate and multivariate COX regression analyses were used to calculate the adjusted hazard ratio (HR), with a 95% confidence interval (CI). In addition, the association between CAR and OS in PD patients was explored by Kaplan-Meier curve and subgroup analysis. Results: This study included 235 PD patients with an average age of 62.25 years, including 135 females and 100 males, and 45 died during the follow-up period. CAR was associated with gender, modified Hoehn-Yahr stages (mH-Y), and Mini-Mental State Examination (MMSE) of PD patients. In the COX multivariate regression model, after adjusting the age, gender, PD duration, mH-Y, MMSE, and the non-steroidal anti-inflammatory drugs, CAR was found to be associated with the OS in PD (HR = 1.54, 95% CI = 1.01-2.34, p = 0.044). Subgroup analysis showed that the subgroup did not play an interactive role in the association between the prognosis of patients with CAR and PD (p for interaction >0.05), and the results remained stable. Conclusions: The all-cause mortality of PD patients with a high level of CAR is higher, which indicates that the poor overall survival of PD patients is associated with the increase of CAR. The CAR may be a reliable prognostic biomarker for PD patients.

Analysis of codon usage patterns in Bupleurum falcatum chloroplast genome.

Objective: In order to distinguish the traditional Chinese medicine Bupleurum falcatum and its adulterants effectively and develop a better understanding of the factors affecting synonymous codon usage, codon usage patterns of chloroplast genome, we determine the complete chloroplast (cp) genome of B. falcatum and clarify the main factors that influence codon usage patterns of 78 genes in B. falcatum chloroplast genome. Methods: The total genomic DNA of fresh leaves from a single individual of B. falcatum was extracted with EASYspin plus Total DNA Isolation Kit and 2 µg genome DNA was sequenced using Illumina Hiseq 2500 Sequencing Platform. The cp genome of B. falcatum was reconstructed with MITObim v1.8 and annotated in the program CPGAVAS2 with default parameters. Python script and Codon W were used to calculate the codon usage bias parameters. Results: The full length of B. falcatum cp genome was 155 851 bp, 132 different genes were annotated in this cp genome containing 80 protein-coding genes, 30 tRNA genes, and four rRNA genes. The codon usage models tended to use A/T-ending codons. The neutrality plot, ENC plot, PR2-Bias plot and correspondence analysis showed that both compositional constraint under selection and mutation could affect the codon usage models in B. falcatum cp genome. Furthermore, three optimal codons were identified and most of these three optimal codons ended with G/U. Conclusion: The cp genome of B. falcatum has been characterized and the codon usage bias in B. falcatum cp genome is influenced by natural selection, mutation pressure and nucleotide composition. The results will provide much more barcode information for species discrimination and lay a foundation for future research on codon optimization of exogenous genes, genetic engineering and molecular evolution in B. falcatum.

Diabetic vascular diseases: molecular mechanisms and therapeutic strategies.

Vascular complications of diabetes pose a severe threat to human health. Prevention and treatment protocols based on a single vascular complication are no longer suitable for the long-term management of patients with diabetes. Diabetic panvascular disease (DPD) is a clinical syndrome in which vessels of various sizes, including macrovessels and microvessels in the cardiac, cerebral, renal, ophthalmic, and peripheral systems of patients with diabetes, develop atherosclerosis as a common pathology. Pathological manifestations of DPDs usually manifest macrovascular atherosclerosis, as well as microvascular endothelial function impairment, basement membrane thickening, and microthrombosis. Cardiac, cerebral, and peripheral microangiopathy coexist with microangiopathy, while renal and retinal are predominantly microangiopathic. The following associations exist between DPDs: numerous similar molecular mechanisms, and risk-predictive relationships between diseases. Aggressive glycemic control combined with early comprehensive vascular intervention is the key to prevention and treatment. In addition to the widely recommended metformin, glucagon-like peptide-1 agonist, and sodium-glucose cotransporter-2 inhibitors, for the latest molecular mechanisms, aldose reductase inhibitors, peroxisome proliferator-activated receptor-γ agonizts, glucokinases agonizts, mitochondrial energy modulators, etc. are under active development. DPDs are proposed for patients to obtain more systematic clinical care requires a comprehensive diabetes care center focusing on panvascular diseases. This would leverage the advantages of a cross-disciplinary approach to achieve better integration of the pathogenesis and therapeutic evidence. Such a strategy would confer more clinical benefits to patients and promote the comprehensive development of DPD as a discipline.

Independent predictive value of blood inflammatory composite markers in ovarian cancer: recent clinical evidence and perspective focusing on NLR and PLR.

Ovarian cancer (OC) is one of the deadliest malignant tumors affecting women worldwide. The predictive value of some blood inflammatory composite markers in OC has been extensively reported. They can be used for early detection and differential diagnosis of OC and can be used for predicting survival, treatment response, and recurrence in the affected patients. Here, we reviewed the predictive values of composite inflammatory markers based on complete blood count, namely neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio, and systemic inflammation index and markers based on blood protein, namely C-reactive protein-to-albumin ratio and prognostic nutritional index in OC, with a focus on NLR and PLR. We referred to the clinical studies on these six markers, reviewed the patient population, and summarized the marker cut-off values, significance, and limitations of these studies. All these studies were retrospective and most of them were single-center clinical studies with small sample sizes. We found that the cut-off values of these markers have not been unified, and methods used to determine these values varied among studies. The predictive value of these markers on survival was mainly reflected in the postoperative patients of multiple subtypes of ovarian cancer including epithelial OC, high-grade serous ovarian carcinoma, and ovarian clear cell carcinoma. We focused on NLR and PLR and calculated their pooled hazard ratios. NLR and PLR were reliable in predicting overall and progression-free survivals in patients with OC. Therefore, it is necessary to adjust important confounding factors and conduct a long-term follow-up prospective cohort study to further clarify the cut-off values of NLR and PLR and their clinical applications.

Ferritinophagy-mediated iron competition in RUTIs: Tug-of-war between UPEC and host.

Uropathogenic Escherichia coli (UPEC) is the main pathogen of recurrent urinary tract infections (RUTIs). Urinary tract infection is a complicated interaction between UPEC and the host. During infection, UPEC can evade the host's immune response and retain in bladder epithelial cells, which requires adequate nutritional support. Iron is the first necessary trace element in life and a key nutritional factor, making it an important part of the competition between UPEC and the host. On the one hand, UPEC grabs iron to satisfy its reproduction, on the other hand, the host relies on iron to build nutritional immunity defenses against UPEC. Ferritinophagy is a selective autophagy of ferritin mediated by nuclear receptor coactivator 4, which is not only a way for the host to regulate iron metabolism to maintain iron homeostasis, but also a key point of competition between the host and UPEC. Although recent studies have confirmed the role of ferritinophagy in the progression of many diseases, the mechanism of potential interactions between ferritinophagy in UPEC and the host is poorly understood. In this paper, we reviewed the potential mechanisms of ferritinophagy-mediated iron competition in the UPEC-host interactions. This competitive relationship, like a tug-of-war, is a confrontation between the capability of UPEC to capture iron and the host's nutritional immunity defense, which could be the trigger for RUTIs. Therefore, understanding ferritinophagy-mediated iron competition may provide new strategies for exploring effective antibiotic alternative therapies to prevent and treat RUTIs.

Research progress and value of albumin-related inflammatory markers in the prognosis of non-small cell lung cancer: a review of clinical evidence.

Inflammatory markers have a wide range of predictive values in the prognosis of non-small lung cancer (NSCLC). Poor nutritional status usually means a poor prognosis in patients with NSCLC, which is widely recognized by oncologists and nutritionists. Serum albumin has a certain value in evaluating the prognosis of patients. Several inflammatory albumin-related markers have been proposed, but they have not been widely used in predicting the prognosis of NSCLC in clinical practice. We aim to systematically review the published clinical evidence of albumin-related inflammatory markers in predicting the prognosis of NSCLC and to describe their progress and value. The results showed that the markers included in the review could be prognostic indicators in patients with NSCLC. However, we found that the cut-off value of albumin-related inflammatory markers with quantitative nature was very chaotic and needed to be defined by recognized standards. We summarized and compared the advantages and disadvantages of these markers, but a prospective cohort study with long-term follow-up after adjustment for important confounders is still necessary. Whether the results and conclusions could be directly applied in clinical practice needs to be identified and evaluated. There is an urgent need to classify and standardize the albumin-related inflammatory markers that play an important role in the prognosis of NSCLC, which is the key to ensuring the transformation from clinical study to clinical application.

Albumin-related inflammatory markers could be prognostic indicators in non-small cell lung cancer.The classification and standardization of albumin-related inflammatory markers guarantee the transformation from clinical study to clinical application.Future prospective studies of albumin-related inflammatory markers excluding confounding factors are very necessary.