Mild therapeutic hypothermic protection activates the PI3K/AKT signaling pathway to inhibit TRPM7 and suppress ferroptosis induced by myocardial ischemia­reperfusion injury.

The present study aimed to investigate the role of PI3K­mediated ferroptosis signaling induced by mild therapeutic hypothermia (MTH), which was defined as a temperature of 34˚C, in protecting against myocardial ischemia-reperfusion (I/R) injury (MIRI). To meet this aim, H9C2 cells underwent hypoxia­reperfusion (H/R) and/or MTH. The MTT assay was used to assess cell viability, cytotoxicity was measured using a lactate dehydrogenase cytotoxicity assay, and Annexin V­FITC/PI flow cytometric analysis was used to analyze early and late cell apoptosis. In addition, 84 healthy adult male Sprague­Dawley rats were randomly divided into seven groups (n=12), and underwent I/R and various treatments. Hemodynamics were monitored, and the levels of myocardial injury marker enzymes and oxidative stress markers in myocardial tissue were measured using ELISA. The expression levels of PI3K, AKT, transient receptor potential cation channel subfamily M member 7 (TRPM7), glutathione peroxidase 4 (GPX4) and acyl­CoA synthetase long chain family member 4 (ACSL4) in animals and cells were measured using western blot analysis. These experiments revealed that MTH could effectively reduce myocardial infarct size, improve hemodynamic performance following MIRI and suppress myocardial apoptosis, thereby contributing to the recovery from H/R injury. Mechanistically, MTH was revealed to be able to activate the PI3K/AKT signaling pathway in cells, upregulating GPX4, and downregulating the expression levels of TRPM7 and ACSL4. Treatment with 2­aminoethoxydiphenyl borate (an inhibitor of TRPM7) could further strengthen the myocardial protective effects of MTH, whereas treatment with erastin (promoter of ferroptosis) and wortmannin (inhibitor of PI3K) led to the effective elimination of the myocardial protective effects of MTH. Compared with in the I/R group, the PI3K/AKT activation level and the expression levels of GPX4 were both significantly increased, whereas the expression levels of TRPM7 and ACSL4 were significantly decreased in the I/R + MTH group. Taken together, the results of the present study indicated that MTH may activate the PI3K/AKT signaling pathway to inhibit TRPM7 and suppress ferroptosis induced by MIRI.

A highly sensitive SERS sensor based on PVDF/Au nanofibers for trace analysis of nitrite ions.

Nitrite ions present a significant risk to both environmental and human health, necessitating precise and sensitive detection methods. Herein, we fabricated a highly sensitive SERS sensor based on PVDF/Au nanofibers for nitrite ion detection. The synthesis of PVDF nanofibers involved the utilization of electrospinning apparatus, while the uniformity and high density of SERS activity "hot spots" were achieved by directly coating plasma gold nanoparticles onto the PVDF surface adopting thermal evaporation. The efficient charge transfer of the interface dipole layer directly generated on the surface of PVDF nanofibers was achieved through thermal evaporation. The enhanced Raman responses were due to the combined effects of local surface plasmon resonance of Au nanoparticles and photoelectric and piezoelectric properties of PVDF. It is noteworthy that the prepared SERS substrate exhibited high sensitivity towards rhodamine 6G, boasting an enhancement factor of 9.4 × 107 and a detection limit spanning from 10-6-10-11 M. Furthermore, the PVDF/Au membrane functionalized with p-aminothiophenol (PATP) effectively captured NO2- ions at concentrations as low as 10-8 M and successfully detected NO2- in river water samples. Additionally, the SERS substrate has good repeatability and stability, and can be applied to trace detection in food safety and medical diagnosis.

Harnessing LLMs for multi-dimensional writing assessment: Reliability and alignment with human judgments.

Recent advancements in natural language processing, computational linguistics, and Artificial Intelligence (AI) have propelled the use of Large Language Models (LLMs) in Automated Essay Scoring (AES), offering efficient and unbiased writing assessment. This study assesses the reliability of LLMs in AES tasks, focusing on scoring consistency and alignment with human raters. We explore the impact of prompt engineering, temperature settings, and multi-level rating dimensions on the scoring performance of LLMs. Results indicate that prompt engineering significantly affects the reliability of LLMs, with GPT-4 showing marked improvement over GPT-3.5 and Claude 2, achieving 112% and 114% increase in scoring accuracy under the criteria and sample-referenced justification prompt. Temperature settings also influence the output consistency of LLMs, with lower temperatures producing scores more in line with human evaluations, which is essential for maintaining fairness in large-scale assessment. Regarding multi-dimensional writing assessment, results indicate that GPT-4 performs well in dimensions regarding Ideas (QWK=0.551) and Organization (QWK=0.584) under well-crafted prompt engineering. These findings pave the way for a comprehensive exploration of LLMs' broader educational implications, offering insights into their capability to refine and potentially transform writing instruction, assessment, and the delivery of diagnostic and personalized feedback in the AI-powered educational age. While this study attached importance to the reliability and alignment of LLM-powered multi-dimensional AES, future research should broaden its scope to encompass diverse writing genres and a more extensive sample from varied backgrounds.

Predicting abrupt depletion of dissolved oxygen in Chaohu lake using CNN-BiLSTM with improved attention mechanism.

Depletion of dissolved oxygen (DO) is a significant incentive for biological catastrophic events in freshwater lakes. Although predicting the DO concentrations in lakes with high-frequency real-time data to prevent hypoxic events is effective, few related experimental studies were made. In this study, a short-term predicting model was developed for DO concentrations in three problematic areas in China's Chaohu Lake. To predict the DO concentrations at these representative sites, which coincide with biological abnormal death areas, water quality indicators at the three sampling sites and hydrometeorological features were adopted as input variables. The monitoring data were collected every 4 h between 2020 and 2023 and applied separately to train and test the model at a ratio of 8:2. A new AC-BiLSTM coupling model of the convolution neural network (CNN) and the bidirectional long short-term memory (BiLSTM) with the attention mechanism (AM) was proposed to tackle characteristics of discontinuous dynamic change of DO concentrations in long time series. Compared with the BiLSTM and CNN-BiLSTM models, the AC-BiLSTM showed better performance in the evaluation criteria of MSE, MAE, and R2 and a stronger ability to capture global dependency relationships. Although the prediction accuracy of hypoxic events was slightly worse, the general time series characteristics of abrupt DO depletion were captured. Water temperature regularly affects DO concentrations due to its periodic variations. The high correlation and the universal importance of total nitrogen (TN) and total phosphorus (TP) with DO reveals that point source pollution are critical cause of DO depletion in the freshwater lake. The importance of NTU at the Zhong Miao Station indicates the self-purification capacity of the lake is affected by the flow rate changes brought by the tributaries. Calculating linear correlations of variables in conjunction with a permutation variable importance analysis enhanced the interpretability of the proposed model results. This study demonstrates that the AC-BiLSTM model can complete the task of short-term prediction of DO concentration of lakes and reveal its response features of timing and magnitude of abrupt DO depletion.

Mild therapeutic hypothermia upregulates the O-GlcNAcylation level of COX10 to alleviate mitochondrial damage induced by myocardial ischemia-reperfusion injury.

OBJECTIVE: Mild therapeutic hypothermia (MTH) is an important method for perioperative prevention and treatment of myocardial ischemia-reperfusion injury (MIRI). Modifying mitochondrial proteins after protein translation to regulate mitochondrial function is one of the mechanisms for improving myocardial ischemia-reperfusion injury. This study investigated the relationship between shallow hypothermia treatment improving myocardial ischemia-reperfusion injury and the O-GlcNAcylation level of COX10. METHODS: We used in vivo Langendorff model and in vitro hypoxia/reoxygenation (H/R) cell model to investigate the effects of MTH on myocardial ischemia-reperfusion injury. Histological changes, myocardial enzymes, oxidative stress, and mitochondrial structure/function were assessed. Mechanistic studies involved various molecular biology methods such as ELISA, immunoprecipitation (IP), WB, and immunofluorescence. RESULTS: Our research results indicate that MTH upregulates the O-GlcNACylation level of COX10, improves mitochondrial function, and inhibits the expression of ROS to improve myocardial ischemia-reperfusion injury. In vivo, MTH effectively alleviates ischemia-reperfusion induced cardiac dysfunction, myocardial injury, mitochondrial damage, and redox imbalance. In vitro, the OGT inhibitor ALX inhibits the OGT mediated O-GlcNA acylation signaling pathway, downregulates the O-Glc acylation level of COX10, promotes ROS release, and counteracts the protective effect of MTH. On the contrary, the OGA inhibitor ThG showed opposite effects to ALX, further confirming that MTH activated the OGT mediated O-GlcNAcylation signaling pathway to exert cardioprotective effects. CONCLUSIONS: In summary, MTH activates OGT mediated O-glycosylation modified COX10 to regulate mitochondrial function and improve myocardial ischemia-reperfusion injury, which provides important theoretical basis for the clinical application of MTH.

Gold Nanorod-Loaded Nano-Contrast Agent with Composite Shell-Core Structure for Ultrasonic/Photothermal Imaging-Guided Therapy in Ischemic Muscle Disorders.

Purpose: This study aims to broaden the application of nano-contrast agents (NCAs) within the realm of the musculoskeletal system. It aims to introduce novel methods, strategies, and insights for the clinical management of ischemic muscle disorders, encompassing diagnosis, monitoring, evaluation, and therapeutic intervention. Methods: We developed a composite encapsulation technique employing O-carboxymethyl chitosan (OCMC) and liposome to encapsulate NCA-containing gold nanorods (GNRs) and perfluoropentane (PFP). This nanoscale contrast agent was thoroughly characterized for its basic physicochemical properties and performance. Its capabilities for in vivo and in vitro ultrasound imaging and photothermal imaging were authenticated, alongside a comprehensive biocompatibility assessment to ascertain its effects on microcirculatory perfusion in skeletal muscle using a murine model of hindlimb ischemia, and its potential to augment blood flow and facilitate recovery. Results: The engineered GNR@OCMC-liposome/PFP nanostructure exhibited an average size of 203.18±1.49 nm, characterized by size uniformity, regular morphology, and a good biocompatibility profile. In vitro assessments revealed NCA's potent photothermal response and its transformation into microbubbles (MBs) under near-infrared (NIR) irradiation, thereby enhancing ultrasonographic visibility. Animal studies demonstrated the nanostructure's efficacy in photothermal imaging at ischemic loci in mouse hindlimbs, where NIR irradiation induced rapid temperature increases and significantly increased blood circulation. Conclusion: The dual-modal ultrasound/photothermal NCA, encapsulating GNR and PFP within a composite shell-core architecture, was synthesized successfully. It demonstrated exceptional stability, biocompatibility, and phase transition efficiency. Importantly, it facilitates the encapsulation of PFP, enabling both enhanced ultrasound imaging and photothermal imaging following NIR light exposure. This advancement provides a critical step towards the integrated diagnosis and treatment of ischemic muscle diseases, signifying a pivotal development in nanomedicine for musculoskeletal therapeutics.

Future Directions in Optimizing Anesthesia to Reduce Perioperative Acute Kidney Injury.

BACKGROUND: Perioperative acute kidney injury (AKI) is common in surgical patients and is associated with high morbidity and mortality. There are currently few options for AKI prevention and treatment. Due to its complex pathophysiology, there is no efficient medication therapy to stop the onset of the injury or repair the damage already done. Certain anesthetics, however, have been demonstrated to affect the risk of perioperative AKI in some studies. The impact of anesthetics on renal function is particularly important as it is closely related to the prognosis of patients. Some anesthetics can induce anti-inflammatory, anti-necrotic, and anti-apoptotic effects. Propofol, sevoflurane, and dexmedetomidine are a few examples of anesthetics that have protective association with AKI in the perioperative period. SUMMARY: In this study, we reviewed the clinical characteristics, risk factors, and pathogenesis of AKI. Subsequently, the protective effects of various anesthetic agents against perioperative AKI and the latest research are introduced. KEY MESSAGE: This work demonstrates that a thorough understanding of the reciprocal effects of anesthetic drugs and AKI is crucial for safe perioperative care and prognosis of patients. However, more complete mechanisms and pathophysiological processes still need to be further studied.

Application of magnetic-nanoparticle functionalized whole-cell biosensor array for bioavailability and ecotoxicity estimation at urban contaminated sites.

The bioavailability and ecotoxicity of pollutants are important for urban ecological systems and human health, particularly at contaminated urban sites. Therefore, whole-cell bioreporters are used in many studies to assess the risks of priority chemicals; however, their application is restricted by low throughput for specific compounds and complicated operations for field tests. In this study, an assembly technology for manufacturing Acinetobacter-based biosensor arrays using magnetic nanoparticle functionalization was developed to solve this problem. The bioreporter cells maintained high viability, sensitivity, and specificity in sensing 28 priority chemicals, seven heavy metals, and seven inorganic compounds in a high-throughput manner, and their performance remained acceptable for at least 20 d. We also tested the performance by assessing 22 real environmental soil samples from urban areas in China, and our results showed positive correlations between the biosensor estimation and chemical analysis. Our findings prove the feasibility of the magnetic nanoparticle-functionalized biosensor array to recognize the types and toxicities of multiple contaminants for online environmental monitoring at contaminated sites.

Polysaccharides-based nanocarriers enhance the anti-inflammatory effect of curcumin.

Curcumin (CUR) has been discovered to have many biological activities, including anti-inflammatory, anti-cancer, anti-oxygenation, anti-human immunodeficiency virus, anti-microbial and exhibits a good effect on the prevention and treatment of many diseases. However, the limited properties of CUR, including the poor solubility, bioavailability and instability caused by enzymes, light, metal irons, and oxygen, have compelled researchers to turn their attention to drug carrier application to overcome these drawbacks. Encapsulation may provide potential protective effects to the embedding materials and/or have a synergistic effect with them. Therefore, nanocarriers, especially polysaccharides-based nanocarriers, have been developed in many studies to enhance the anti-inflammatory capacity of CUR. Consequently, it's critical to review current advancements in the encapsulation of CUR using polysaccharides-based nanocarriers, as well as further study the potential mechanisms of action where polysaccharides-based CUR nanoparticles (the complex nanoparticles/Nano CUR-delivery systems) exhibit their anti-inflammatory effects. This work suggests that polysaccharides-based nanocarriers will be a thriving field in the treatment of inflammation and inflammation-related diseases.

Regulation of NcRNA-protein binding in diabetic foot.

Non-coding RNA (ncRNA) is a special type of RNA transcript that makes up more than 90 % of the human genome. Although ncRNA typically does not encode proteins, it indirectly controls a wide range of biological processes, including cellular metabolism, development, proliferation, transcription, and post-transcriptional modification. NcRNAs include small interfering RNA (siRNA), PIWI-interacting RNA (piRNA), tRNA-derived small RNA (tsRNA), etc. The most researched of these are miRNA, lncRNA, and circRNA, which are crucial regulators in the onset of diabetes and the development of associated consequences. The ncRNAs indicated above are linked to numerous diabetes problems by binding proteins, including diabetic foot (DF), diabetic nephropathy, diabetic cardiomyopathy, and diabetic peripheral neuropathy. According to recent studies, Mir-146a can control the AKAP12 axis to promote the proliferation and migration of diabetic foot ulcer (DFU) cells, while lncRNA GAS5 can activate HIF1A/VEGF pathway by binding to TAF15 to promote DFU wound healing. However, there are still many unanswered questions about the mechanism of action of ncRNAs. In this study, we explored the mechanism and new progress of ncRNA-protein binding in DF, which can provide help and guidance for the application of ncRNA in the early diagnosis and potential targeted intervention of DFU.

Bioinspired Macrocyclic Molecule Supported Two-Dimensional Lamellar Membrane with Robust Interlayer Structure for High-Efficiency Nanofiltration.

2D lamellar membranes (2DLMs) are used for efficient desalination and nanofiltration. However, weak interactions between adjacent stacked nanosheets result in susceptibility to swelling that limits practical applicability. Inspired by the super adhesion of multi-point suction cups on octopus tentacles, a 2DLM is constructed from Ti3 C2 Tx MXene supported by the macrocyclic "multi-point" molecule cucurbit[5]uril (CB5) and demonstrated for nanofiltration of methyl blue (MB) and enrichment of uranyl carbonate. Experimental results and density functional theory calculations indicate that CB5 rivets to the surface of the nanoflakes through strong stable interactions between its multiple binding sites and surface hydroxyl functional groups on MXene nanosheets. This novel 2DLM exhibits excellent nanofiltration performance (69 L m-2 h-1 bar-1 permeance with 93.6% rejection for MB) and can be recycled at least 30 times without significant degradation. The 2DLM exhibits excellent swelling resistance at high salinity, with a demonstration of selective enrichment of uranyl carbonate from artificial water and natural seawater. The results provide a new strategy for constructing highly stable 2DLMs with interlayer spacing controllable from sub-nano to nanometer scales, for size-selective sieving of molecules and ions, high-efficiency nanofiltration, and other applications.

Nanoscale Contrast Agents for Ultrasound Imaging of Musculoskeletal System.

Musculoskeletal ultrasound (MSKUS) has been recognized as an important method for the evaluation of diseases of the musculoskeletal system, and contrast-enhanced ultrasound (CEUS) technology is becoming an important branch of it. The development of novel materials and tiny nano-formulations has further expanded ultrasound contrast agents (UCAs) into the field of nanotechnology. Over the years, nanoscale contrast agents have been found to play an unexpected role in the integration of precise imaging for diagnosis and treatment of numerous diseases. It has been demonstrated that nanoscale UCAs (nUCAs) have advantages in imaging over conventional contrast agents, including superior biocompatibility, serum stability, and longer lifetime. The potential value of nUCAs in the musculoskeletal system is that they provide more reliable and clinically valuable guidance for the diagnosis, treatment, and follow-up of related diseases. The frontier of advances in nUCAs, their applications, and insights in MSKUS are reviewed in this paper.

Non-steroidal anti-inflammatory drugs and clinical outcomes in patients with COVID-19.

The use of non-steroidal anti-inflammatory drugs (NSAIDs) in patients with coronavirus disease 2019 (COVID-19) has raised great concerns. The effect of NSAIDs on the clinical status of COVID-19 remains in question. Therefore, we performed a post-hoc analysis from the ORCHID trial. Patients with COVID-19 from the ORCHID trial were categorized into two groups according to NSAID use. The 28-day mortality, hospitalized discharge, and safety outcomes with NSAIDs for patients with COVID-19 were analyzed. A total of 476 hospitalized patients with COVID-19 were included; 412 patients (86.5%) did not receive NSAIDs, while 64 patients (13.5%) took NSAIDs as regular home medication. Patients who took NSAIDs did not have a significant increase in the risk of 28-day mortality (fully adjusted: hazard ratio [HR]: 1.12, 95% CI: 0.52-2.42) in the Cox multivariate analysis. Moreover, NSAIDs did not decrease hospital discharge through 28 days (fully adjusted: HR: 1.02, 95% CI: 0.75-1.37). The results of a meta-analysis including 14 studies involving 48,788 patients with COVID-19 showed that the use of NSAIDs had a survival benefit (summary risk ratio [RR]: 0.70, 95% CI: 0.54-0.91) and decreased the risk of severe COVID-19 (summary: RR: 0.79, 95% CI: 0.71-0.88). In conclusion, the use of NSAIDs is not associated with worse clinical outcomes, including 28-day mortality or hospital discharge in American adult hospitalized patients with COVID-19. Based on current evidence, the use of NSAIDs is safe and should not be cautioned against during the COVID-19 pandemic. Ongoing trials should further assess in-hospital treatment with NSAIDs for patients with COVID-19.

MicroRNAs in Kawasaki disease: An update on diagnosis, therapy and monitoring.

Kawasaki disease (KD) is an acute autoimmune vascular disease featured with a long stage of febrile. It predominantly afflicts children under 5 years old and causes an increased risk of cardiovascular combinations. The onset and progression of KD are impacted by many aspects, including genetic susceptibility, infection, and immunity. In recent years, many studies revealed that miRNAs, a novel class of small non-coding RNAs, may play an indispensable role in the development of KD via differential expression and participation in the central pathogenesis of KD comprise of the modulation of immunity, inflammatory response and vascular dysregulation. Although specific diagnose criteria remains unclear up to date, accumulating clinical evidence indicated that miRNAs, as small molecules, could serve as potential diagnostic biomarkers and exhibit extraordinary specificity and sensitivity. Besides, miRNAs have gained attention in affecting therapies for Kawasaki disease and providing new insights into personalized treatment. Through consanguineous coordination with classical therapies, miRNAs could overcome the inevitable drug-resistance and poor prognosis problem in a novel point of view. In this review, we systematically reviewed the existing literature and summarized those findings to analyze the latest mechanism to explore the role of miRNAs in the treatment of KD from basic and clinical aspects retrospectively. Our discussion helps to better understand the pathogenesis of KD and may offer profound inspiration on KD diagnosis, treatment, and prognosis.

AMPK: The key to ischemia-reperfusion injury.

Ischemia-reperfusion injury (IRI) refers to a syndrome in which tissue damage is further aggravated and organ function further deteriorates when blood flow is restored after a period of tissue ischemia. Acute myocardial infarction, stress ulcer, pancreatitis, intestinal ischemia, intermittent claudication, acute tubular necrosis, postshock liver failure, and multisystem organ failure are all related to reperfusion injury. AMP-activated protein kinase (AMPK) has been identified in multiple catabolic and anabolic signaling pathways. The functions of AMPK during health and diseases are intriguing but still need further research. Except for its conventional roles as an intracellular energy switch, emerging evidence reveals the critical role of AMPK in IRI as an energy-sensing signal molecule by regulating metabolism, autophagy, oxidative stress, inflammation, and other progressions. At the same time, drugs based on AMPK for the treatment of IRI are constantly being researched and applied in clinics. In this review, we summarize the mechanisms underlying the effects of AMPK in IRI and describe the AMPK-targeting drugs in treatment, hoping to increase the understanding of AMPK in IRI and provide new insights into future clinical treatment.

Research progress on ncRNAs regulation of mitochondrial dynamics in diabetes.

Diabetes mellitus and its complications are major health concerns worldwide that should be routinely monitored for evaluating disease progression. And there is currently much evidence to suggest a critical role for mitochondria in the common pathogenesis of diabetes and its complications. Mitochondrial dynamics are involved in the development of diabetes through mediating insulin signaling and insulin resistance, and in the development of diabetes and its complications through mediating endothelial impairment and other closely related pathophysiological mechanisms of diabetic cardiomyopathy (DCM). noncoding RNAs (ncRNAs) are closely linked to mitochondrial dynamics by regulating the expression of mitochondrial dynamic-associated proteins, or by regulating key proteins in related signaling pathways. Therefore, this review summarizes the research progress on the regulation of Mitochondrial Dynamics by ncRNAs in diabetes and its complications, which is a promising area for future antibodies or targeted drug development.

Obesity and clinical outcomes in COVID-19 patients without comorbidities, a post-hoc analysis from ORCHID trial.

Objective: Large body of studies described individuals with obesity experiencing a worse prognosis in COVID-19. However, the effects of obesity on the prognosis of COVID-19 in patients without comorbidities have not been studied. Therefore, the current study aimed to provide evidence of the relationship between obesity and clinical outcomes in COVID-19 patients without comorbidities. Methods: A total of 116 hospitalized COVID-19 patients without comorbidities from the ORCHID study (Patients with COVID-19 from the Outcomes Related to COVID-19 Treated with Hydroxychloroquine among Inpatients with Symptomatic Disease) were included. Obesity is defined as a BMI of ≥30 kg/m2. A Cox regression analysis was used to estimate the hazard ratio (HR) for discharge and death after 28 days. Results: The percentage of obesity in COVID-19 patients without comorbidities was 54.3% (63/116). Discharge at 28 days occurred in 56/63 (84.2%) obese and 51/53 (92.2%) non-obese COVID-19 patients without comorbidities. Four (3.4%) COVID-19 patients without any comorbidities died within 28 days, among whom 2/63 (3.2%) were obese and 2/53 (3.8%) were non-obese. Multivariate Cox regression analyses showed that obesity was independently associated with a decreased rate of 28-day discharge (adjusted HR: 0.55, 95% CI: 0.35-0.83) but was not significantly associated with 28-day death (adjusted HR: 0.94, 95% CI: 0.18-7.06) in COVID-19 patients without any comorbidities. Conclusions: Obesity was independently linked to prolonged hospital length of stay in COVID-19 without any comorbidity. Larger prospective trials are required to assess the role of obesity in COVID-19 related deaths.

Therapeutic hypothermia alleviates myocardial ischaemia-reperfusion injury by inhibiting inflammation and fibrosis via the mediation of the SIRT3/NLRP3 signalling pathway.

Therapeutic hypothermia (TH) may attenuate myocardial ischaemia-reperfusion injury, thereby improving outcomes in acute myocardial infarction. However, the specific mechanism by which TH alleviates MIRI has not been elucidated so far. In this study, 120 healthy male Sprague-Dawley rats were randomly divided into five groups. Haemodynamic parameters, myocardial infarction area, histological changes and the levels of cardiac enzymes, caspase-1 and inflammatory cytokines were determined. In addition, the extent of myocardial fibrosis, the degree of cardiomyocyte apoptosis and the expression levels of SIRT3, GSDMD-N, fibrosis-related proteins and inflammation-related proteins were estimated.TH reduced myocardial infarct area and cardiac enzyme levels, improved cardiomyopathic damage and haemodynamic indexes, and attenuated myocardial fibrosis, the protein expression levels of collagen I and III, myocardial apoptosis, the levels of inflammatory cytokines and inflammation-related proteins. Notably, the immunofluorescence and protein expression levels of SIRT3 were upregulated in the 34H+DMSO group compared to the I/R group, but this protective effect was abolished by the SIRT3 inhibitor 3-TYP. After administration of Mcc950, the reversal effects of 3-TYP were significantly abolished, and TH could protect against MIRI in a rat isolated heart model by inhibiting inflammation and fibrosis. The SIRT3/NLRP3 signalling pathway is one of the most important signalling pathways in this regard.

Colchicine linked with risk reduction for myocardial infarction in gout patients: systematic review and meta-analysis.

INTRODUCTION: This meta-analysis aimed to identify the effect of colchicine on myocardial infarction (MI) in patients with gout. METHODS: In February 2021, a systematic computer-based search was conducted in PubMed, EMBASE, and Cochrane Database of Systematic Reviews. Data on patients with gout that compared colchicine versus others (no use of colchicine) were retrieved. The endpoints were the incidence rate for MI. After testing for heterogeneity between studies, data were aggregated for fixed-effects models when necessary. RESULTS: Three clinical studies with 3012 patients (colchicine group = 1523, control group = 1489) were finally included in the meta-analysis. Colchicine was associated with a decreased risk for myocardial infarction (pooled odds ratio 0.35, 95% confidence interval 0.23-0.55, p < 0.00001). CONCLUSIONS: Colchicine was effective in reducing the incidence of MI in patients with gout.

Modular Assembly of Isostructural Mixed-Ligand Uranyl Coordination Polymers Based on a Patterning Strategy.

Controlling the orderly assembly of molecular building blocks for the formation of the desired architectural, chemical, and physical properties of the resulting solid-state materials remains a long-term goal and deserves to be examined. In this work, we propose a patterning strategy for modular assembly and structural regulation of mixed-ligand uranyl coordination polymers (CPs) through the combination of couples of organic ligands with complementary molecular geometry and well-matched coordination modes. By using a 5-(p-tolyldiazenyl)isophthalic acid ligand (H2ptdi) with different rigid linear bicarboxylic acid linkers to construct a well-defined ladder-like pattern, five novel isostructural uranyl coordination polymers, [(UO)2(ptdi)(bdc)0.5](dma) (1), [(UO)2(ptdi)(bpdc)0.5](dma) (2), [(UO)2(ptdi)(tpdc)0.5](dma) (3), [(UO)2(ptdi)(ndc)0.5](dma) (4), and [(UO)2(ptdi) (pdc)0.5](dma) (5) {H2bdc, 1,4-dicarboxybenzene; H2bpdc, 4,4'-biphenyldicarboxylic acid; H2tpdc, terphenyl-4,4″-dicarboxylic acid; H2ndc, 2,6-naphthalenedicarboxylic acid; H2pdc, 1,6-pyrenedicarboxylic acid; [dma]+, [(CH3)2NH2]+}, were successfully synthesized. Structural analysis reveals that 1-5 have similar ladder-like units but different sizes of one-dimensional nanochannels and interlayer spacing due to the different lengths and widths of the linkers. Because of the changes in interlayer spacing of these isostructural cationic frameworks, differences in the performance of Eu3+ ion exchange with [dma]+ are observed. Moreover, those compounds with high phase purity have been further characterized by thermogravimetric analysis, infrared spectroscopy, and luminescence spectroscopy, element analysis, PXRD and UV spectroscopy. Among them, compound 3 with strong fluorescence can selectively detect Fe3+ over several competing metal cations in aqueous solution. This work not only provides a feasible patterning method for effectively regulating the modular synthesis of functional coordination polymers but also enriches the library of uranyl-based coordination polymers with intriguing structures and functionality.