Peptide-Driven Assembly of Magnetic Beads for Potentiometric Sensing of Bacterial Enzyme at a Subcellular Level.

Bacterial enzymes with different subcellular localizations play a critical ecological role in biogeochemical processing. However, precisely quantifying enzymes localized at certain subcellular levels, such as extracellular enzymes, has not yet been fully realized due to the complexity and dynamism of the bacterial outer membrane. Here we present a magneto-controlled potentiometric sensing platform for the specific detection of extracellular enzymatic activity. Alkaline phosphatase (ALP), which is one of the crucial hydrolytic enzymes in the ocean, was selected as the target enzyme. Magnetic beads functionalized with an ALP-responsive self-assembled peptide (GGGGGFFFpYpYEEE, MBs-peptides) prevent negatively charged peptides from entering the bacterial outer membrane, thereby enabling direct potentiometric sensing of extracellular ALP both attached to the bacterial cell surface and released into the surrounding environment. The dephosphorylation-triggered assembly of peptide-coupled magnetic beads can be directly and sensitively measured by using a magneto-controlled sensor. In this study, extracellular ALP activity of Pseudomonas aeruginosa at concentrations ranging from 10 to 1.0 × 105 CFU mL-1 was specifically and sensitively monitored. Moreover, this magneto-controlled potentiometric method enabled a simple and accurate assay of ALP activity across different subcellular localizations.

Enhanced Selectivity in Microdroplet-Mediated Enzyme Catalysis.

Natural enzymes with enhanced catalytic activity and selectivity have long been studied by tuning the microenvironment around the active site, but how to modulate the active-site electric field in a simple fashion remains challenging. Here, we demonstrate that microdroplets as a simple yet versatile reactor can enhance the electric field at the active site of an enzyme. By using horseradish peroxidase as a model, improved selectivity in microdroplet-mediated enzyme catalysis can be obtained. Quantum mechanical/molecular dynamics calculations and vibrational Stark spectroscopy reveal that the electric field at the microdroplet interface can influence the electrostatic preorganization and orientation of the enzyme to enhance its internal electric field. As a result, the free energies of the substrate and heme can be tuned by the internal electric field, thereby changing its catalytic reaction pathway for a classical substrate, 3,3',5,5'-tetramethylbenzidine, and enabling selective C-N additions for specific substrates. This finding provides a green, simple, and effective way to modulate enzyme-catalyzed reactions and holds promise for a broad spectrum of biosensing and biosynthesis applications.

Where the cerebral infarction meets child, be vigilant about patent foramen ovale: a case report.

Background: While cerebral infarction in children is rare, its prognosis is poor, and this condition can seriously burden society and families. A correlation between patent foramen ovale (PFO) and ischemic stroke has not been found in pediatric patients. Case presentation: We report a 7-year-old boy who suffered from multiple cerebral infarctions. Subsequently, the patient was diagnosed with an abnormal shunt of PFO. He underwent PFO closure and was followed up for 1 year. The patient did not experience any further cerebral infarction. Conclusions: With this case report, we want to illustrate that although the incidence rate of ischemic cerebral infarction in adolescents is very low, we should not neglect the role of PFO. Therefore, after exclusion other causes of cerebral infarction, PFO should be considered in adolescent and adult stroke patients with adult closure criteria in the same way.

Chronopotentiometric sensors for antimicrobial peptide-based biosensing of Staphylococcus aureus.

Charged antimicrobial peptides can be used for direct potentiometric biosensing, but have never been explored. We report here a galvanostatically-controlled potentiometric sensor for antimicrobial peptide-based biosensing. Solid-state pulsed galvanostatic sensors that showed excellent stability under continuous galvanostatic polarization were prepared by utilizing reduced graphene oxide/poly (3,4-ethylenedioxythiophene): poly (4-styrenesulfonate) (rGO/PEDOT: PSS) as a solid contact. More importantly, the chronopotentiometric sensor can be made sensitive to antimicrobial peptides with intrinsic charge on demand via a current pulse. In this study, a positively charged antimicrobial peptide that can bind to Staphylococcus aureus with high affinity and good selectivity was designed as a model. Two arginine residues with positive charges were linked to the C-terminal of the peptide sequence to increase its potentiometric responses on the electrode. The bacteria binding-induced charge or charge density change of the antimicrobial peptide enables the direct chronopotentiometric detection of the target. Under the optimized conditions, the concentration of Staphylococcus aureus can be determined in the linear range 10-1.0 × 105 CFU mL-1 with a detection limit of 10 CFU mL-1. It is anticipated that such a chronopotentiometric sensing platform is readily adaptable to detect other bacteria by choosing the peptides.

Rapid antibiotic screening based on E. coli apoptosis using a potentiometric sensor array.

Phenotypic antimicrobial susceptibility testing enables reliable antibiotic screening but requires multiple strategies to identify each phenotypic change induced by different bactericidal mechanisms. Bacteria apoptosis with typical phenotypic features has never been explored for antibiotic screening. Herein, we developed an antibiotic screening method based on the measurement of antibiotic-induced phosphatidylserine (PS) exposure of apoptotic bacteria. Phosphatidylserine externalization of E. coli that can be widely used as an apoptosis marker for antibiotics with different antibacterial mechanisms was explored. A positively charged PS-binding peptide was immobilized on magnetic beads (MBs) to recognize and capture apoptotic E. coli with PS externalization. Apoptotic E. coli binding led to the charge or charge density change of MBs-peptide, resulting in a potential change on a magneto-controlled polymeric membrane potentiometric sensor. Based on the detection of apoptotic E. coli killed by antibiotics, antibiotic screening for different classes of antibiotics and silver nanoparticles was achieved within 1.5 h using a potentiometric sensor array. This approach enables sensitive, general, and time-saving antibiotic screening, and may open up a new path for antibiotic susceptibility testing.

Role of C/EBP Homologous Protein in Vascular Stenosis After Carotid Artery Injury.

The study aims to explore the fluctuating expression of C/EBP Homologous Protein (CHOP) following rat carotid artery injury and its central role in vascular stenosis. Using in vivo rat carotid artery injury models and in vitro ischemia and hypoxia cell models employing human aortic endothelial cells (HAECs) and vascular smooth muscle cells (T/G HA-VSMCs), a comprehensive investigative framework was established. Histological analysis confirmed intimal hyperplasia in rat models. CHOP expression in vascular tissues was assessed using Western blot and immunohistochemical staining, and its presence in HAECs and T/G HA-VSMCs was determined through RT-PCR and Western blot. The study evaluated HAEC apoptosis, inflammatory cytokine secretion, cell proliferation, and T/G HA-VSMCs migration through Western blot, ELISA, CCK8, and Transwell migration assays. The rat carotid artery injury model revealed substantial fibrous plaque formation and vascular stenosis, resulting in an increased intimal area and plaque-to-lumen area ratio. Notably, CHOP is markedly elevated in vessels of the carotid artery injury model compared to normal vessels. Atorvastatin effectively mitigated vascular stenosis and suppresses CHOP protein expression. In HAECs, ischemia and hypoxia-induced CHOP upregulation, along with heightened TNFα, IL-6, caspase3, and caspase8 levels, while reducing cell proliferation. Atorvastatin demonstrated a dose-dependent suppression of CHOP expression in HAECs. Downregulation of CHOP or atorvastatin treatment led to reduced IL-6 and TNFα secretion, coupled with augmented cell proliferation. Similarly, ischemia and hypoxia conditions increased CHOP expression in T/G HA-VSMCs, which was concentration-dependently inhibited by atorvastatin. Furthermore, significantly increased MMP-9 and MMP-2 concentrations in the cell culture supernatant correlated with enhanced T/G HA-VSMCs migration. However, interventions targeting CHOP downregulation and atorvastatin usage curtailed MMP-9 and MMP-2 secretion and suppressed cell migration. In conclusion, CHOP plays a crucial role in endothelial injury, proliferation, and VSMCs migration during carotid artery injury, serving as a pivotal regulator in post-injury fibrous plaque formation and vascular remodeling. Statins emerge as protectors of endothelial cells, restraining VSMCs migration by modulating CHOP expression.

Adverse Drug Events Observed with the Newly Approved Remimazolam in Comparison to Propofol for General Anesthesia in Patients Undergoing Surgery: A Meta-analysis.

INTRODUCTION: Developments in anesthetic pharmacology have been aiming at minimizing physiological disturbance in addition to maintaining and improving titrateability, recovery profile, and patient experience. Remimazolam, a GABAAlpha receptor agonist, is a new intravenous anesthetic agent which has recently been approved for use. This analysis aimed to systematically compare the adverse drug events reported with the newly approved remimazolam in comparison to propofol for general anesthesia (GA) in patients undergoing surgery. METHODS: Electronic databases were searched from 15 May to 20 December 2023 for relevant publications which compared the outcomes reported with the newly approved remimazolam versus propofol in patients undergoing surgery. Relevant reported adverse drug events were the endpoints of this study. The statistical analysis was carried out using the latest version of the RevMan software. Data analysis was represented by risk ratio (RR) with 95% confidence intervals (CI). RESULTS: Sixteen studies with a total number of 1897 participants were included in this analysis; 1104 participants received remimazolam and 793 participants received propofol. The risks for hypotension (RR 0.50, 95% CI 0.43-0.58; P = 0.00001), hypoxemia (RR 0.43, 95% CI 0.19-0.99; P = 0.05), bradycardia (RR 0.53, 95% CI 0.36-0.78; P = 0.001), pain at injection site (RR 0.07, 95% CI 0.01-0.56; P = 0.01), and total adverse events (RR 0.33, 95% CI 0.24-0.47; P = 0.00001) were significantly lower with remimazolam. However, no significant differences were observed in terms of postoperative nausea and vomiting (RR 0.98, 95% CI 0.66-1.46; P = 0.93), dizziness (RR 0.42, 95% CI 0.11-1.57; P = 0.20), psychiatric symptoms (RR 1.09, 95% CI 0.45-2.67; P = 0.85), and respiratory depression (RR 0.81, 95% CI 0.24-2.76; P = 0.74). CONCLUSION: Our current analysis showed that the newly approved remimazolam was apparently associated with significantly fewer adverse drug events in comparison to propofol for GA in patients undergoing surgery. Therefore, this new drug should be further studied and more research with larger population sizes should be carried out to confirm this hypothesis.

Robust Potentiometric Microelectrodes for In Situ Sensing of Ion Fluxes with High Sensitivity.

Simple, reproducible, and reliable preparation of robust potentiometric microelectrodes is both challenging and of great importance for noninvasive real-time ion sensing. Herein, we report a simple strategy for the large-scale synthesis of nickel cobalt sulfide (NiCo2S4) nanowire arrays grown on carbon fibers for potentiometric microelectrodes. The highly uniform NiCo2S4 nanowire array serving as a transduction layer can provide a high capillary pressure and viscous resistance for loading the ion sensing membrane and exhibit a large redox capacitance for improving the stability. An all-solid-state lead-selective microelectrode, which presents a detection limit of 2.5 × 10-8 M in the simulated soil solution, was designed as a model for noninvasive, in situ, and real-time detection of ion fluxes near the rice root surface. Importantly, the microsensor enables sensitive detection of trace-level ion-fluxes. This work provides a simple yet general strategy for designing potentiometric microelectrodes.

Glutamate secretion by embryonic stem cells as an autocrine signal to promote proliferation.

Glutamate, the major excitatory neurotransmitter in the central nervous system, has also been found to play a role in embryonic stem (ES) cells. However, the exact mechanism and function of glutamatergic signaling in ES cells remain poorly understood. In this study, we identified a glutamatergic transmission circuit in ES cells that operates through an autocrine mechanism and regulates cell proliferation. We performed biological analyses to identify the key components involved in glutamate biosynthesis, packaging for secretion, reaction, and reuptake in ES cells, including glutaminase, vesicular glutamate transporter, glutamate N-methyl-D-aspartate (NMDA) receptor, and cell membrane excitatory amino-acid transporter (EAAT). We directly quantified the released glutamate signal using microdialysis-high performance liquid chromatography-tandem mass spectrometry (MD-HPLC-MS-MS). Pharmacological inhibition of endogenous glutamate release and the resulting tonic activation of NMDA receptors significantly affected ES cell proliferation, suggesting that ES cells establish a glutamatergic autocrine niche via releasing and responding to the transmitter for their own regulation.

Near-Infrared Laser Irradiation-Modulated High-Temperature Solid-Contact Ion-Selective Electrodes: Potentiometric Detection of Ca2+ in Seawater.

The high-temperature potentiometry operated by nonisothermal heating is a promising way to break through the traditional potentiometric responses of ion-selective electrodes (ISEs) at room temperature. Herein, a locally heated strategy through near-infrared region (NIR) laser irradiation upon the photothermal mesoporous carbon material placed between the ion-selective membrane and the glassy carbon substrate is introduced to obtain the high-temperature potentiometric performance of a solid-contact Ca2+-ISE for detection of Ca2+ in seawater. Based on the light-to-heat conversion of the mesoporous carbon-based solid contact, the temperature of the solid-contact Ca2+-ISE upon continuous NIR laser irradiation can be increased from room temperature to 60-70 °C, and the slope of the electrode is promoted up to about 30% according to the thermodynamic steady-state potentiometric response. The pulsed potentiometric response of the solid-contact Ca2+-ISE upon a pulsed NIR laser irradiation of 5 s also shows a linear change as a function of Ca2+ activities, and the improved slope from 27.1 ± 0.6 to 38.1 ± 0.9 mV/dec can be obtained under dual control of the temperature of the electrode and the transient current induced by the pulsed NIR laser irradiation. As compared to the traditional potentiometric measurement under zero-current conditions at room temperature, the NIR laser-modulated high-temperature potentiometric response provides an alternative way for measurement of the solid-contact ISEs.

Modern Potentiometric Biosensing Based on Non-Equilibrium Measurement Techniques.

Modern potentiometric sensors based on polymeric membrane ion-selective electrodes (ISEs) have achieved new breakthroughs in sensitivity, selectivity, and stability and have extended applications in environmental surveillance, medical diagnostics, and industrial analysis. Moreover, nonclassical potentiometry shows promise for many applications and opens up new opportunities for potentiometric biosensing. Here, we aim to provide a concept to summarize advances over the past decade in the development of potentiometric biosensors with polymeric membrane ISEs. This Concept article articulates sensing mechanisms based on non-equilibrium measurement techniques. In particular, we emphasize new trends in potentiometric biosensing based on attractive dynamic approaches. Representative examples are selected to illustrate key applications under zero-current conditions and stimulus-controlled modes. More importantly, fruitful information obtained from non-equilibrium measurements with dynamic responses can be useful for artificial intelligence (AI). The combination of ISEs with advanced AI techniques for effective data processing is also discussed. We hope that this Concept will illustrate the great possibilities offered by non-equilibrium measurement techniques and AI in potentiometric biosensing and encourage further innovations in this exciting field.

Effectively facilitating the degradation of chloramphenicol by the synergism of Shewanella oneidensis MR-1 and the metal-organic framework.

Electroactive bacteria (EAB) and metal oxides are capable of synergistically removing chloramphenicol (CAP). However, the effects of redox-active metal-organic frameworks (MOFs) on CAP degradation with EAB are not yet known. This study investigated the synergism of iron-based MOFs (Fe-MIL-101) and Shewanella oneidensis MR-1 on CAP degradation. 0.5 g/L Fe-MIL-101 with more possible active sites led to a three-fold higher CAP removal rate in the synergistic system with MR-1 (initial bacterial concentration of 0.2 at OD600), and showed a superior catalytic effect than exogenously added Fe(III)/Fe(II) or magnetite. Mass spectrometry revealed that CAP was transformed into smaller molecular weight and less toxic metabolites in cultures. Transcriptomic analysis showed that Fe-MIL-101 enhanced the expression of genes related to nitro and chlorinated contaminants degradation. Additionally, genes encoding hydrogenases and c-type cytochromes associated with extracellular electron transfer were significantly upregulated, which may contribute to the simultaneous bioreduction of CAP both intracellularly and extracellularly. These results indicated that Fe-MIL-101 can be used as a catalyst to synergize with EAB to effectively facilitate CAP degradation, which might shed new light on the application in the in situ bioremediation of antibiotic-contaminated environments.

In Situ Continuous Measurement of Salinity in Estuarine and Coastal Sediments by All-Solid Potentiometric Sensors.

Salinity is crucial for understanding the environmental and ecological processes in estuarine and coastal sediments. In situ measurements in sediments are scarce due to the low water content and particulate adsorption. Here, a new potentiometric sensor principle is proposed for the real-time in situ measurement of salinity in sediments. The sensor system is based on paper sampling and two all-solid electrodes, a cation-selective electrode (copper hexacyanoferrate, CuHCF) and an anion-selective electrode (Ag/AgCl). The spontaneous aqueous electrolyte extraction and redox reaction can produce a Nernstian response on both electrodes that is directly related to salinity. This potentiometric sensor allows for salinity acquisition in a wide salinity range (1-50 ppt), with high resolution (<1 ppt), and at a low water content (<30%), and it has been applied for the in situ measurement of salinity and the interpretation of cycling processes of metals in estuarine and coastal sediments. Moreover, the sensor coupled to a wireless monitoring system exhibited remote-sensing capability and successfully captured the salinity dynamic processes of the overlying water and pore water during the tidal period. This sensor with its low cost, versatility, and applicability represents a valuable tool to advance the comprehension of salinity and the salinity-driven dissolved-matter variations in estuarine and coastal sediments.

Deep Learning-Enhanced Potentiometric Aptasensing with Magneto-Controlled Sensors.

Bioelectronic sensors that report charge changes of a biomolecule upon target binding enable direct and sensitive analyte detection but remain a major challenge for potentiometric measurement, mainly due to Debye Length limitations and the need for molecular-level platforms. Here, we report on a magneto-controlled potentiometric method to directly and sensitively measure the target-binding induced charge change of DNA aptamers assembled on magnetic beads using a polymeric membrane potentiometric ion sensor. The potentiometric responses of the negatively charged aptamer, serving as a receptor and reporter, were dynamically controlled and modulated by applying a magnetic field. Based on a potentiometric array, this non-equilibrium measurement technique combined with deep learning algorithms allows for rapidly and reliably classifying and quantifying diverse small molecules using antibiotics as models. This potentiometric strategy opens new modalities for sensing applications.

Analysis of cardiovascular disease factors on SARS-CoV-2 infection severity.

Background: At present, COVID-19 is a global pandemic and is seriously harmful to humans. In this retrospective study, the aim was to investigate the interaction between CVD and COVID-19. Methods: A total of 180 patients diagnosed with COVID-19 in Yichang Central People's Hospital from 29 January to 17 March 2020 were initially included. The medical history, clinical manifestations at the time of admission, laboratory test results, hospitalization time and complications were recorded. According to the medical history, the patients were assigned to the nonsevere group with non-CVD (n = 90), the nonsevere group with CVD (n = 22), the severe group with non-CVD (n = 40) and the severe group with CVD (n = 28). Results: In the severe group, compared with non-CVD patients, CVD patients had a significantly higher incidence of fever (P < 0.05). However, compared with the nonsevere group, the severe group had significantly higher proportions of patients with hypertension, type 2 diabetes mellitus, CHD and HF (all P < 0.05). Among the patients with nonsevere COVID-19, the WBC count and the levels of IL-6, CRP, D-dimer, NT-proBNP, and FBG were significantly higher and the Hb level was significantly lower in the CVD patients than in the non-CVD patients (all P < 0.05). However, among the patients with severe COVID-19, only the level of NT-proBNP was significantly higher in CVD patients than in non-CVD patients (P < 0.05). In addition, the WBC count and the levels of IL-6, CRP, D-dimer, CKMB, ALT, AST, SCR, NT-proBNP, and FBG were significantly higher and the Hb level was significantly lower in the severe group than in the nonsevere group (all P < 0.05). However, among the patients with severe COVID-19, the incidences of acute myocardial injury, acute kidney injury, arrhythmia, and sudden death were significantly higher in the CVD group than in the non-CVD group (all P < 0.05). The same results were found in the comparison of the nonsevere group with the severe group. Among the patients with nonsevere COVID-19, those without CVD had a mean hospitalization duration of 25.25 (SD 7.61) days, while those with CVD had a mean hospitalization duration of 28.77 (SD 6.11) days; the difference was significant (P < 0.05). The same results were found in the comparison of the severe group. Conclusions: CVD affects the severity of COVID-19. COVID-19 also increases the risk of severe CVD.

Antecedentes: La infección por SARS-CoV-2 está provocando graves consecuencias en la humanidad. El objetivo de este estudio retrospectivo fue investigar el impacto de las enfermedades cardiovasculares (ECV) en la gravedad de dicha infección. Métodos: Entre el 29 de enero y el 17 de marzo de 2020, se diagnosticaron 180 pacientes con neumonía por SARS-CoV-2 en el Hospital Popular Central de Yichang. Se registraron los antecedentes, manifestaciones clínicas, resultados de laboratorio, tiempo de hospitalización y complicaciones. Los pacientes se dividieron en cuatro grupos: 1) infección no grave sin ECV (n = 90), 2) infección no grave con ECV (n = 22), 3) infección grave sin ECV (n = 40) y 4) infección grave con ECV (n = 28). Resultados: La prevalencia de fiebre en los pacientes con ECV fue significativamente mayor que en aquellos sin ECV (P < 0,05). Sin embargo, en comparación con los pacientes no graves, la proporción de pacientes con hipertensión, diabetes mellitus tipo 2, cardiopatía coronaria e insuficiencia cardíaca en los pacientes graves fue significativamente mayor (p< 0,05). Los niveles de recuento de leucocitos, IL-6, PCR, dímero D, NT-proBNP y glucemia en ayunas (GA) en pacientes con ECV fueron significativamente mayores que en los de pacientes sin ECV, aunque los niveles de Hb fueron significativamente menores que los de los pacientes sin ECV (p< 0,05). Sin embargo, los valores de NT-proBNP en pacientes con ECV fueron significativamente mayores que en los pacientes sin ECV (P< 0,05). Además, el recuento de leucocitos y los niveles de IL-6, PCR, dímero D, CK-MB, ALT, AST, creatinina, NT-proBNPy GA en el grupo de pacientes graves fueron significativamente mayores que en el grupo no grave, mientras que los valores de Hb fueron significativamente menores que en el grupo no grave (p< 0,05). La prevalencia de lesión miocárdica aguda, lesión renal aguda, arritmia y muerte súbita en el grupo con ECV fue significativamente mayor que en el grupo sin ECV (p< 0,05). Los mismos resultados se encontraron al comparar los pacientes no graves con aquellos con infección grave. Entre los pacientes no graves, la duración media de la estancia hospitalaria fue de 25,25 (DE: 7,61) días en los pacientes sin ECV, mientras que la duración media de la estancia hospitalaria fue de 28,77 (DE: 6,11) días en los pacientes con ECV (p< 0,05). Los mismos resultados se observaron al comparar los dos grupos con infección grave. Conclusiones: La infección por SARS-CoV-2 es de evolución más grave en los pacientes con ECV.

New progress in diagnosis and treatment of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive disease. Although great progress has been made in its diagnosis and treatment in recent years, its mortality rate is still very significant. The pathophysiology and pathogenesis of PAH are complex and involve endothelial dysfunction, chronic inflammation, smooth muscle cell proliferation, pulmonary arteriole occlusion, antiapoptosis and pulmonary vascular remodeling. These factors will accelerate the progression of the disease, leading to poor prognosis. Therefore, accurate etiological diagnosis, treatment and prognosis judgment are particularly important. Here, we systematically review the pathophysiology, diagnosis, genetics, prognosis and treatment of PAH.

Application of Medical Knowledge Graphs in Cardiology and Cardiovascular Medicine: A Brief Literature Review.

A knowledge graph is defined as a collection of interlinked descriptions of concepts, relationships, entities and events. Medical knowledge graphs have been the most recent advances in technology, therapy and medicine. Nowadays, a number of specific uses and applications rely on knowledge graphs. The application of the knowledge graph, another form of artificial intelligence (AI) in cardiology and cardiovascular medicine, is a new concept, and only a few studies have been carried out on this particular aspect. In this brief literature review, the use and importance of disease-specific knowledge graphs in exploring various aspects of Kawasaki disease were described. A vision of individualized knowledge graphs (iKGs) in cardiovascular medicine was also discussed. Such iKGs would be based on a modern informatics platform of exchange and inquiry that could comprehensively integrate biologic knowledge with medical histories and health outcomes of individual patients. This could transform how clinicians and scientists discover, communicate and apply new knowledge. In addition, we also described how a study based on the comprehensive longitudinal evaluation of dietary factors associated with acute myocardial infarction and fatal coronary heart disease used a knowledge graph to show the dietary factors associated with cardiovascular diseases in Nurses' Health Study data. To conclude, in this fast-developing world, medical knowledge graphs have emerged as attractive methods of data storage and hypothesis generation. They could be a major and effective tool in cardiology and cardiovascular medicine and play an important role in reaching effective clinical decisions during treatment and management of patients in the cardiology department.

Exercise Intervention as a Therapy in Patients with Diabetes Mellitus and Sarcopenia: A Meta-Analysis.

INTRODUCTION: Sarcopenia is defined as a progressive and generalized muscle disorder that involves accelerated loss of muscle mass and impaired function. It is believed to influence the ability to carry out daily activities, muscle strength, and physical capacity in the elderly. Studies have shown that sarcopenia has been implicated as both a cause and a consequence of diabetes mellitus. In this analysis, we aimed to systematically show the impact of exercise intervention as a therapy for patients with diabetes mellitus and sarcopenia. METHODS: Electronic databases, including PubMed, EMBASE, Web of Science, and the Cochrane database, were searched from November to December 2021 for publications based on exercise intervention in patients with sarcopenia. After the selection of studies for this analysis, patients with diabetes mellitus were retrieved. Since dichotomous data including mean and standard deviation were reported, weighted mean difference (MD) with 95% confidence intervals (CI) were used to represent the data following analysis. RESULTS: A total of 431 participants with diabetes mellitus and sarcopenia were included in this meta-analysis. A statistical analysis was carried out on patients with diabetes mellitus who were assigned to the exercise intervention group. Our analysis showed that "sit-to-stand test" and "timed up and go" were significantly in favor of exercise intervention: MD -1.57, 95% confidence interval (CI) -2.26 to -0.87 (P = 0.0001) versus MD -0.61, 95% CI -1.21 to -0.01 (P = 0.05), respectively. Handgrip strength, walking speed and leg strength were also assessed. Another statistical analysis was carried out, this time on patients with diabetes mellitus and sarcopenia who were not assigned to an exercise intervention. The results showed no significant difference among sit-to-stand test, timed up and go, handgrip strength, and leg strength. CONCLUSION: Exercise intervention significantly improved the time taken to stand up from a sitting position, and to "stand up and go" in patients with diabetes mellitus and sarcopenia. Therefore, exercise intervention should be considered a relevant therapy for such patients.

The critical role and molecular mechanisms of ferroptosis in antioxidant systems: a narrative review.

Background and Objective: Ferroptosis is a recently discovered form of cell death which differs from other forms of cell death in terms of morphology, biochemistry, and regulatory mechanisms. Ferroptosis is regulated by a complex system and the precise molecular mechanisms are still being elucidated. Over the past few years, extensive research has revealed that the essence of ferroptosis is iron-dependent accumulation of lipid hydroperoxides induced by oxidative stress, and the System Xc-glutathione (GSH)-glutathione peroxidase 4 (GPX4) pathway is the main ferroptosis prevention system. Meanwhile, other antioxidant systems have also been implicated in regulating ferroptosis, including the transsulfuration pathway, mevalonate pathway, ferroptosis inhibitory protein 1 (FSP1)-Coenzyme Q10 (CoQ10) pathway, dihydroorotate dehydrogenase (DHODH)-dihydroubiquione (CoQH2) pathway, and GTP cyclohydrolase-1 (GCH1)-tetrahydrobiopterin (BH4) pathway. This article reviews the molecular mechanisms of ferroptosis and its critical role in antioxidant systems, aiming to reveal that antioxidation is an important method of inhibiting ferroptosis and to provide a new direction for the treatment of ferroptosis-related diseases. Methods: We searched all original papers and reviews about the molecular mechanisms of ferroptosis in antioxidant systems using PubMed to November 2021. The search terms used included: 'ferroptosis', 'ferroptosis inducers', 'ferroptosis inhibitors', 'ferroptosis and GSH', 'ferroptosis and GPX4', 'ferroptosis and System Xc-', 'SLC7A11', 'P53', 'NRF2 and ferroptosis', 'iron metabolism', 'lipid peroxidation', 'antioxidant systems', 'transsulfuration pathway', 'mevalonate pathway', 'FSP1-CoQ10', 'DHODH-CoQH2', and 'GCH1-BH4'. Key Content and Findings: We first introduced the origin of ferroptosis and its common inhibitors and inducers. Next, we discussed the molecular mechanisms of ferroptosis and its role in antioxidant systems in existing studies. Finally, we briefly summarized the relationship between ferroptosis and diseases. It reveals that antioxidation is an important method of inhibiting ferroptosis. Conclusions: This review discusses the recent rapid progress in the understanding of the molecular mechanisms of ferroptosis and its role in several antioxidant systems.

Permanent His-bundle pacing in the right atrium in a patient with a Mobitz II atrioventricular block: a case presentation.

BACKGROUND: This case report presents a patient diagnosed with sick sinus syndrome who was successfully treated with permanent His-bundle pacing (PHBP). CASE PRESENTATION: A 36-year-old man was transferred to our hospital due to recurrent syncope. He was diagnosed with sick sinus syndrome based on the 24-h Holter and a history of syncope. He was admitted to hospital and successfully treated with PHBP. The postoperative examination showed that the pacing rhythm, pacemaker pacing and perception function were normal. He was discharged without any complications after a successful pacemaker implantation. CONCLUSIONS: We described a case in which PHBP may become an optimal approach to the management of patients with sick sinus syndrome. Right ventricular pacing has been attempted with inconsistent efficacy outcomes. HBP provides a promising alternative pacing option that might provide symptom resolution to patients with sick sinus syndrome.