Upregulation of GPX4 drives ferroptosis resistance in scleroderma skin fibroblasts.

The pathogenesis of systemic sclerosis (SSC) fibrosis involves the rapid proliferation of skin fibroblasts, and current anti-fibrotic treatments are limited. This study investigated the relationship between ferroptosis and SSC skin fibroblasts. We observed that erastin-induced ferroptosis was suppressed in SSC fibroblasts. RSL3, a direct inhibitor of Glutathione Peroxidase 4 (GPX4), significantly reduced the viability of the fibroblasts, and upregulation of GPX4 in the SSC fibroblasts contributed to ferroptosis resistance. Furthermore, we demonstrated that transferrin receptor 1 (TfR1) was a crucial transporter for iron deposition in the fibroblasts. Collectively, our results highlight that GPX4 inhibition could enhance the sensitivity to ferroptosis by SSC fibroblasts, which showed distinct characteristics of iron metabolism that were not observed in normal fibroblasts in this study. Taken together, these results suggest that targeting ferroptosis could be a therapeutic strategy for the treatment of SSC.

Evaluation of Renal Microhemodynamics Heterogeneity in Different Strains and Sexes of Mice.

Addressing the existing gaps in our understanding of sex- and strain-dependent disparities in renal microhemodynamics, this study conducts an investigation into the variations in renal function and related biological oscillators. Utilizing the genetically diverse mouse models BALB/c, C57BL/6, and KM, which serve as established proxies for the study of renal pathophysiology, we implemented laser Doppler flowmetry conjoined with wavelet transform analyses to interrogate the dynamic renal microcirculation. Creatinine, urea, uric acid, glucose, and cystatin C, were quantified to investigate potential divergences attributable to sex and genetic lineage. Our findings reveal marked sexual dimorphism in metabolite concentrations, as well as strain-specific variances, particularly in creatinine and cystatin C levels. Through the combination of Mantel tests and Pearson's correlation coefficients, we delineated the associations between renal functional metrics and microhemodynamics, uncovering interactions in female BALB/c mice for creatinine and uric acid, and in male C57BL/6 mice for cystatin C. Histopathological examination confirmed an augmented microvascular density in females and elucidating variations in the expression of estrogen receptor ß amongst the strains. These data collectively highlight the influence of both sex and genetic constitution on renal microcirculation, providing an understanding that may inform the etiological exploration of renal ailments.

Cognitive Function and Medication Adherence in Older Adults With H-Type Hypertension: The Mediating Effect of Metamemory.

PURPOSE: Medication adherence in adults with H-type hypertension plays a crucial role in lowering blood pressure and treating complications. Cognitive function has been identified as a significant influencing factor for medication adherence, whereas excessive levels of homocysteine can impair cognitive function. Metamemory, which is influenced by cognitive function, also affects medication adherence. However, the complex relationship among these factors remains poorly understood among adults with H-type hypertension. Therefore, we hypothesize that metamemory serves as a mediator for the impact of cognitive function on medication adherence. METHOD: A total of 232 adults with H-type hypertension were enrolled to provide cognitive function scores, metamemory scores, and medication adherence rates. RESULTS: A pairwise correlation exists among cognitive function, metamemory, and medication adherence. Metamemory partially mediates (57.5%) the relationship between cognitive function and medication adherence. CONCLUSION: Our findings suggest that interventions targeting improvements in metamemory may enhance medication adherence among individuals with H-type hypertension. [Journal of Gerontological Nursing, 50(6), 44-52.].

Dataset on cardiac structural and functional parameters in TMAO-challenged mouse.

Trimethylamine-N-oxide (TMAO) is a gut-derived metabolite formed from dietary choline and l-carnitine, known to impede cholesterol metabolism and is implicated in the pathogenesis of thrombosis and atherosclerosis, contributing to the etiology of cardiovascular diseases. We present a dataset derived from an experimental study designed to elucidate the cardiotoxic effects of TMAO. This dataset encompasses echocardiographic assessments from two cohorts of mice: one subjected to a 6-week regimen of 20 mg/kg/day TMAO injections (n = 16) and a control group (n = 18). Each subject's echocardiographic dataset comprises six high-resolution TIFF images, capturing both B-type and M-mode views in standard echocardiographic planes, along with two additional M-mode images enriched with analysed cardiac functional data. Complementing these images, a CSV-formatted report details critical cardiac parameters, including heart rate, ejection fraction, and fractional shortening, among others. In a novel approach to enhance data integrity and permit tailored analyses, we provide the original output files from the echocardiography apparatus, which researchers can reprocess using dedicated analysis software. This dataset is anticipated to be instrumental in advancing our understanding of the mechanistic links between TMAO exposure and cardiac dysfunction.

Efficacy of botanical lozenges in the treatment of chronic pharyngitis: a randomized controlled trial.

Background: In clinical practice, antibiotics and/or inhaled or oral hormone preparations are the first line of treatment for chronic pharyngitis. However, this therapeutic regimen is not satisfactory enough. At present, medicinal plants as dietary supplements or functional foods are widely recognized for the treatment and prevention of different diseases. Purpose: This study aimed to evaluate the efficacy of the botanical lozenge made from several medicinal plant extracts in the treatment of chronic pharyngitis and its effects on patients' illness perception and adherence to treatment. Methods: Patients with chronic pharyngitis were randomly assigned to the experimental group (n = 52) or the control group (n = 51). Patients were given botanical lozenges prepared from the extracts of medicinal plants such as Siraitia grosvenorii (Swingle) C. Jeffrey ex A.M.Lu and Zhi Y. Zhang [Cucurbitaceae; Siraitiae fructus], Lonicera japonica Thunb [Caprifoliaceae; Lonicerae japonicae flos], Platycodon grandiflorus (Jacq.) A. DC [Campanulaceae; Platycodon radix], and Glycyrrhiza uralensis Fisch. ex DC [Fabaceae; Glycyrrhizae radix et rhizoma] or placebos made of starch for 15 days. The improvement of pharyngeal symptoms and signs, illness perception, and adherence to treatment were evaluated at the end of the intervention. Results: The total score of pharyngeal symptoms of patients in the experimental group (3.33 ± 2.33) was significantly lower than that in the control group (5.20 ± 2.93) (p < 0.01). In comparison to the control group (3.43 ± 1.43), the total pharyngeal signs score of patients in the experimental group (2.69 ± 1.59) was considerably lower (p < 0.01). The improvement rates of pharyngeal itching, dry throat, pharyngeal foreign body sensation, aggravation due to excessive speaking, and congestion of pharyngeal mucosa in the experimental group were 73.81%, 67.50%, 67.57%, 65.22% and 44%, respectively, which were significantly higher than those in the control group (p < 0.05). In addition, patients taking botanical lozenges had better illness perception and adherence to treatment than those taking placebos (p < 0.05). Patients with low adherence to treatment showed less personal control, concerns, and understanding of chronic pharyngitis (p < 0.05). Conclusion: Botanical lozenges not only aided patients in recovering from chronic pharyngitis but also improved their positive perceptions of the disease, which helped them adhere to their treatment regimen. Clinical Trial Registration: [https://www.chictr.org.cn/], identifier [ChiCTR2200062139].

Endoscopic treatment for early duodenal papillary carcinoma: long-term outcomes.

BACKGROUND AND AIM: This study aims to determine whether endoscopic papillectomy (EP) is a safe and effective treatment for early duodenal papillary carcinoma with long-term follow-up. METHODS: From June 2012 to September 2022, 48 patients with early duodenal papilloma carcinoma who received endoscopic treatment were included. The histological types, percentage of complete resections, postoperative residuals, adverse events, and recurrences were evaluated. RESULTS: EP was successful in all patients; 46 were lumped, and two were fragmented, with a 95.8% intact removal rate (46/48). The preoperative biopsy pathological positive rate was 70.8% (34/48). The incidence of early postoperative adverse events (within 1 month after EP) were 16.7% (8/48), including four cases of acute pancreatitis, three cases of delayed bleeding, and one case of acute cholangitis. In addition, 4.2% (2/48) of the late adverse events were bile duct stenosis. After 6 months, the postoperative residual rate was 0%. The median time to recurrence was 17.5 months, and the postoperative recurrence rate was 16.7% (8/48) in patients treated with radiofrequency ablation. The median progression-free survival was 18.6 months (95% CI, 12.1-25.1), and the median overall survival was 121.5 months (95% CI, 105.6-120.9). CONCLUSIONS: EP is a safe and efficient alternative therapy for early duodenal papillary carcinoma. Endoscopic follow-up and treatment are essential because of the potential for recurrence.

Tiny clue reveals the general trend: a bibliometric and visualized analysis of renal microcirculation.

BACKGROUND: Renal microcirculation plays a pivotal role in kidney function by maintaining structural and functional integrity, facilitating oxygen and nutrient delivery, and waste removal. However, a thorough bibliometric analysis in this area remains lacking. Therefore, we aim to provide valuable insights through a bibliometric analysis of renal microcirculation literature using the Web of Science database. METHODS: We collected renal microcirculation-related publications from the Web of Science database from January 01, 1990, to December 31, 2022. The co-authorship of authors, organizations, and countries/regions was analyzed with VOSviewer1.6.18. The co-occurrence of keywords and co-cited references were analyzed using CiteSpace6.1.R6 software to generate visualization maps. Additionally, burst detection was applied to keywords and cited references to forecast research hotspots and future trends. RESULTS: Our search yielded 7462 publications, with the American Journal of Physiology-Renal Physiology contributing the most articles. The United States, Mayo Clinic, and Lerman Lilach O emerged with the highest publication count, indicating their active collaborations. 'Type 2 diabetes' was the most significant keyword cluster, and 'diabetic kidney disease' was the largest cluster of cited references. 'Cardiovascular outcome' and 'diabetic kidney diseases' were identified as keywords in their burst period over the past three years. CONCLUSION: Our bibliometric analysis illuminates the contours of nephrology and microcirculation research, revealing a landscape ripe for challenges and the seeds of future scientific innovation. While the trends discerned from the literature emerging opportunities in diagnostic innovation, renal microcirculation research, and precision medicine interventions, their translation to clinical practice is anticipated to be a deliberate process.

Insights into optimal surgical fixation for posterior malleolar fractures.

Aims: The optimal management of posterior malleolar ankle fractures, a prevalent type of ankle trauma, is essential for improved prognosis. However, there remains a debate over the most effective surgical approach, particularly between screw and plate fixation methods. This study aims to investigate the differences in outcomes associated with these fixation techniques. Methods: We conducted a comprehensive review of clinical trials comparing anteroposterior (A-P) screws, posteroanterior (P-A) screws, and plate fixation. Two investigators validated the data sourced from multiple databases (MEDLINE, EMBASE, and Web of Science). Following PRISMA guidelines, we carried out a network meta-analysis (NMA) using visual analogue scale and American Orthopaedic Foot and Ankle Score (AOFAS) as primary outcomes. Secondary outcomes included range of motion limitations, radiological outcomes, and complication rates. Results: The NMA encompassed 13 studies, consisting of four randomized trials and eight retrospective ones. According to the surface under the cumulative ranking curve-based ranking, the A-P screw was ranked highest for improvements in AOFAS and exhibited lowest in infection and peroneal nerve injury incidence. The P-A screws, on the other hand, excelled in terms of VAS score improvements. Conversely, posterior buttress plate fixation showed the least incidence of osteoarthritis grade progression, postoperative articular step-off ≥ 2 mm, nonunions, and loss of ankle dorsiflexion ≥ 5°, though it underperformed in most other clinical outcomes. Conclusion: The NMA suggests that open plating is more likely to provide better radiological outcomes, while screw fixation may have a greater potential for superior functional and pain results. Nevertheless, clinicians should still consider the fragment size and fracture pattern, weighing the advantages of rigid biomechanical fixation against the possibility of soft-tissue damage, to optimize treatment results.

A novel class of inhibitors that disrupts the stability of integrin heterodimers identified by CRISPR-tiling-instructed genetic screens.

The plasma membrane is enriched for receptors and signaling proteins that are accessible from the extracellular space for pharmacological intervention. Here we conducted a series of CRISPR screens using human cell surface proteome and integrin family libraries in multiple cancer models. Our results identified ITGAV (integrin αV) and its heterodimer partner ITGB5 (integrin ß5) as the essential integrin α/ß pair for cancer cell expansion. High-density CRISPR gene tiling further pinpointed the integral pocket within the ß-propeller domain of ITGAV for integrin αVß5 dimerization. Combined with in silico compound docking, we developed a CRISPR-Tiling-Instructed Computer-Aided (CRISPR-TICA) pipeline for drug discovery and identified Cpd_AV2 as a lead inhibitor targeting the ß-propeller central pocket of ITGAV. Cpd_AV2 treatment led to rapid uncoupling of integrin αVß5 and cellular apoptosis, providing a unique class of therapeutic action that eliminates the integrin signaling via heterodimer dissociation. We also foresee the CRISPR-TICA approach to be an accessible method for future drug discovery studies.

Low-Temperature and Fast-Charge Sodium Metal Batteries.

Low-temperature operation of sodium metal batteries (SMBs) at the high rate faces challenges of unstable solid electrolyte interphase (SEI), Na dendrite growth, and sluggish Na+ transfer kinetics, causing a largely capacity curtailment. Herein, low-temperature and fast-charge SMBs are successfully constructed by synergetic design of the electrolyte and electrode. The optimized weak-solvation dual-salt electrolyte enables high Na plating/stripping reversibility and the formation of NaF-rich SEI layer to stabilize sodium metal. Moreover, an integrated copper sulfide electrode is in situ fabricated by directly chemical sulfuration of copper current collector with micro-sized sulfur particles, which significantly improves the electronic conductivity and Na+ diffusion, knocking down the kinetic barriers. Consequently, this SMB achieves the reversible capacity of 202.8 mAh g-1 at -20 °C and 1 C (1 C = 558 mA g-1 ). Even at -40 °C, a high capacity of 230.0 mAh g-1 can still be delivered at 0.2 C. This study is encouraging for further exploration of cryogenic alkali metal batteries, and enriches the electrode material for low-temperature energy storage.

Improved Photovoltaic Performance of Inverted Two-Dimensional Perovskite Solar Cells via a Simple Molecular Bridge on Buried Interface.

NiOx-based two-dimensional perovskite solar cells (2D-PSCs) have the advantages of low fabrication temperature, suitable energy level matching, suppressed hysteresis, and superior stability, while the poor interfacial contacts between NiOx and perovskite layers limit the perovskite film growth and charge transfer. Herein, a simple molecule, urea, was used as a molecular modifier to form bifacial passivation on the buried interface of NiOx/perovskite, resulting in better interfacial contact and efficient bifacial passivation. We demonstrated that efficient bifacial passivation mainly comes from strong interactions between urea and NiOx or perovskite, which make urea a molecular bridge for smoother charge transfer. Moreover, urea can regulate the ratio of Ni3+/Ni2+, therefore boosting the conductivity of NiOx, and adjust the morphology of the NiOx film for better 2D-perovskite crystal growth. Besides, urea also passivates the bifacial defect states of both NiOx and perovskite film, yielding reduced defect density of the perovskite film and superior charge transfer on the buried interface. Consequently, inverted 2D-PSCs with urea modification proved significant improvements in short-circuit current density and fill factor, resulting in improved power conversion efficiency from 14.64 to 16.84% with better stability in air.

Ultra-sensitive molecular residual disease detection through whole genome sequencing with single-read error correction.

While whole genome sequencing (WGS) of cell-free DNA (cfDNA) holds enormous promise for molecular residual disease (MRD) detection, its performance is limited by WGS error rate. Here we introduce AccuScan, an efficient cfDNA WGS technology that enables genome-wide error correction at single read level, achieving an error rate of 4.2×10 -7 , which is about two orders of magnitude lower than a read-centric de-noising method. When applied to MRD detection, AccuScan demonstrated analytical sensitivity down to 10 -6 circulating tumor allele fraction at 99% sample level specificity. In colorectal cancer, AccuScan showed 90% landmark sensitivity for predicting relapse. It also showed robust MRD performance with esophageal cancer using samples collected as early as 1 week after surgery, and predictive value for immunotherapy monitoring with melanoma patients. Overall, AccuScan provides a highly accurate WGS solution for MRD, empowering circulating tumor DNA detection at parts per million range without high sample input nor personalized reagents. One Sentence Summary: AccuScan showed remarkable ultra-low limit of detection with a short turnaround time, low sample requirement and a simple workflow for MRD detection.

Bulk bismuth anodes for wide-temperature sodium-ion batteries enabled by electrolyte chemistry modulation.

Sodium ion batteries (SIBs) are considered reliable supplies for next-generation energy devices. However, there is a limited understanding of strategies to prevent the performance deterioration of SIBs under extreme temperature conditions. This study aimed to address this challenge by developing modified electrolyte chemistry to achieve stable wide-temperature SIBs. Weakly Na+-solvating solvent 2-methyltetrahydrofuran (MeTHF) was used to promote the kinetics of Na+ de-solvation. Moreover, 1,2-dimethoxyethane (DME) was introduced as a co-solvent because of the high solubility for Na salts and the coupling reaction mechanism with the Bi electrode. The formulated electrolyte not only endows an anion-dominated NaF-rich solid electrolyte interface (SEI) layer, but also reduces the energy required for the Na+ across the SEI layer (from 291.2 to 89.6 meV). Consequently, Na||Bi half batteries achieve stable cycles at 400 mA g-1 at -20, 20 and 60 °C, respectively. Meanwhile, the extreme operating temperature of the batteries can be extended to -40 and 80 °C, which exceeds those of most current lithium/sodium-based batteries. Furthermore, full batteries employing Na3V2(PO4)3 as the cathode material exhibit stable operation over a wide temperature range of -20 to 60 °C. This electrolyte design strategy presented in this study shows significant promise for enabling wide-temperature SIBs with improved performance.

Xanthohumol attenuates collagen synthesis in scleroderma skin fibroblasts by ROS/Nrf2/TGFß1/Smad3 pathway.

Skin fibrosis, the most obvious clinical manifestation of systemic sclerosis (SSc), has a high unmet need for treatment. Xanthohumol (Xn) has been shown to have beneficial effects on fibrotic diseases, but its efficacy in SSc remains unreported. This study aims to elucidate the effects and mechanisms of Xn on collagen synthesis in SSc skin fibroblasts (SScF). We found increased collagen production in SScF cultured in vitro, accompanied by dysregulated levels of oxidative stress. Cell experiments showed that Xn inhibited cell proliferation and promoted apoptosis. In addition, Xn was shown for the first time to upregulate reactive oxygen species (ROS) and nuclear factor erythroid 2-related factor 2 (Nrf2)levels in SScF, and when combined with the ROS scavenger N-acetylcysteine (NAC), Nrf2 expression was decreased. Importantly, we demonstrated that Xn significantly attenuated collagen synthesis by blocking the fibrotic classical transforming growth factor beta 1 (TGFß1)/Smad3 pathway, which interestingly was upregulated when combined with the Nrf2 inhibitor 385. Taken together, Xn suppressed the TGFß1/Smad3 pathway to ameliorate collagen overproduction by promoting ROS-induced oxidative stress damage and activating Nrf2, suggesting that Xn administration may be an emerging therapeutic strategy for skin fibrosis in SSc.

Gualou xiebai decoction ameliorates cardiorenal syndrome type II by regulation of PI3K/AKT/NF-κB signalling pathway.

BACKGROUND: Cardiorenal syndromes type II (CRS2) is a multi-organ ailment that manifests as a combination of cardiac and renal dysfunction, resulting in chronic kidney disease due to chronic cardiac insufficiency. It affects at least 26 million people worldwide, and its prevalence is increasing. Gualou Xiebai Decoction (GXD), a traditional Chinese medicine (TCM) with a rich history of application in the management of coronary artery disease, has been explored for its potential therapeutic benefits in CRS2. Nevertheless, the mechanism by which GXD alleviates CRS2 remains obscure, necessitating further investigation. PURPOSE: The aim of this study was to assess the effects of the ethanolic extract of GXD on CRS2 and to elucidate the underlying mechanism in a rat model of myocardial infarction, offering a potential target for clinical treatment for CRS2. STUDY DESIGN AND METHODS: A rat model of CRS2 was induced by surgical myocardial infarction and treated with GXD for 10 weeks. Cardiac function was assessed using echocardiography, while serum and urine biochemistry were analyzed to evaluate potential cardiac and renal damage. Furthermore, tissue samples were obtained for histological, protein, and genetic investigations. In addition, network pharmacology analysis and molecular docking were utilized to predict the primary active compounds, potential therapeutic targets, and interventional pathways through which GXD could potentially exert its effects on CRS2. Subsequently, these predictions were confirmed in vivo and vitro through various analyses. RESULTS: The current investigation employed echocardiography to exhibit the apparent cardiac remodeling following the induction of myocardial infarction. Damage to the heart and kidneys of CRS2 rats was effectively ameliorated by administration of GXD. The outcomes derived from the analyses of HE and Masson staining indicated that the pathological damage to the heart and kidney tissues of rats in the GXD groups was considerably alleviated. Using network pharmacology analysis, AKT1, IL-6, and TNF-α were identified as plausible therapeutic targets for the treatment of CRS with GXD. Subsequent functional and pathway enrichment analysis of the underlying targets disclosed that the PI3K/AKT/NF-κB signaling pathway may be involved in the mechanism of GXD in the treatment of CRS2. Immunohistochemical, western blot, RT-PCR and immunofluorescence staining were employed to demonstrate that GXD can regulate the PI3K/AKT/NF-κB signaling pathway in the CRS2 rat model. Ultimately, administration of the PI3K/AKT agonist 740Y-P counteracted the effect of diosmetin, which was one of the potential active components of GXD analysed by compound-target-disease network, on p-PI3K and p-AKT in vitro. CONCLUSIONS: The findings of this study suggest that GXD improves cardiac and renal function in CRS2 rats and that the underlying mechanism involves inhibition of the PI3K/AKT/NF-κB pathway.

An Ultra-Low-Temperature Alternating Current Filter.

Traditional alternating current filter based on aluminum electrolytic capacitors (AECs) suffer from abrupt drop of filtering capability at ultra-low temperatures (≤-30 °C), which greatly hinders the reliable working of electronics at extremely cold conditions. Herein, an ultra-low-temperature alternating current (AC) filter for the first time enabled by high-frequency supercapacitor based on covalently bonded hollow carbon onion-graphene hybrid structure is reported. It is found that the covalent bonding junctions enable high electronic conductivity and efficient ion adsorption/desorption behavior in the hybrid structure. Moreover, the hybrid structure owns positive curvature and shallows pores for fast ion diffusion kinetics. Consequently, the supercapacitor exhibits a record short resistor-capacitor time constant (τRC ) of 0.098 ms at 120 Hz at room temperature. Combining with low-melting-point electrolyte, the supercapacitor possesses excellent filtering capability and can output stable direct current signal with low fluctuation coefficients in a temperature range of -50 to 0 °C. More interestingly, the filter presents high negative phase angle, low dissipation factor, short τRC , and high capacitance retention below -30 °C, whereas AEC cannot work properly owing to its phase angle<45°. This work realizes the fabrication of an ultra-low-temperature AC filter, which presents a critical step forward for promoting the development of ultra-low-temperature electronics.

Determining the Optimal Treatment for Idiopathic Clubfoot: A Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Clubfoot, or congenital talipes equinovarus deformity, is a common anomaly affecting the foot in infants. However, clinical equipoise remains between different interventions, especially those based on the Ponseti method. The aim of this study was to examine the clinical outcomes of the various interventions for treating idiopathic clubfoot. METHODS: Searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Scopus, and CINAHL were conducted. Randomized controlled trials comparing different interventions, including the Ponseti method, accelerated Ponseti method, Ponseti method with botulinum toxin type A (Botox) injection, Ponseti method with early tibialis anterior tendon transfer (TATT), Kite method, and surgical treatment, were included. Network meta-analyses (NMAs) were conducted according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) reporting guidelines. The primary outcomes were the change in total Pirani score and maximal ankle dorsiflexion. Secondary outcomes were the number of casts, time in casts, and rates of tenotomy, total complications, relapse, adverse events, and additional required major surgery. RESULTS: Eleven randomized controlled trials involving 740 feet were included. According to the SUCRA (surface under the cumulative ranking curve)-based relative ranking, the Ponseti method was associated with the best outcomes in terms of Pirani score changes, maximal ankle dorsiflexion, number of casts, adverse events, and total complications, whereas the accelerated Ponseti method was associated with the best outcomes in terms of time in casts and tenotomy rate. Early TATT ranked best in terms of relapse rate. The Ponseti method with Botox injection was associated with the best outcomes in terms of the need for additional major surgery. CONCLUSIONS: The NMAs suggest that the Ponseti method is the optimal treatment overall, despite potential drawbacks such as longer time in casts and higher rates of tenotomy, relapse, and the need for additional surgery compared with other modified approaches. Therefore, clinicians should consider how treatments can be tailored individually. LEVEL OF EVIDENCE: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Realizing Low-Temperature Graphite-based Rechargeable Potassium-Ion Full Battery.

Graphite (Gr) has been considered as the most promising anode material for potassium-ion batteries (PIBs) commercialization due to its high theoretical specific capacity and low cost. However, Gr-based PIBs remain unfeasible at low temperature (LT), suffering from either poor kinetics based on conventional carbonate electrolytes or K+ -solvent co-intercalation issue based on typical ether electrolytes. Herein, a high-performance Gr-based LT rechargeable PIB is realized for the first time by electrolyte chemistry. Applying unidentate-ether-based molecule as the solvent dramatically weakens the K+ -solvent interactions and lowers corresponding K+ de-solvation kinetic barrier. Meanwhile, introduction of steric hindrance suppresses co-intercalation of K+ -solvent into Gr, greatly elevating operating voltage and cyclability of the full battery. Consequently, the as-prepared Gr||prepotassiated 3,4,9,10-perylene-tetracarboxylicacid-dianhydride (KPTCDA) full PIB can reversibly charge/discharge between -30 and 45 °C with a considerable energy density up to 197 Wh kgcathode -1 at -20 °C, hopefully facilitating the development of LT PIBs.

Harnessing the benefits of glycine supplementation for improved pancreatic microcirculation in type 1 diabetes mellitus.

Type 1 diabetes mellitus (T1DM) is predominantly managed using insulin replacement therapy, however, pancreatic microcirculatory disturbances play a critical role in T1DM pathogenesis, necessitating alternative therapies. This study aimed to investigate the protective effects of glycine supplementation on pancreatic microcirculation in T1DM. Streptozotocin-induced T1DM and glycine-supplemented mice (n = 6 per group) were used alongside control mice. Pancreatic microcirculatory profiles were determined using a laser Doppler blood perfusion monitoring system and wavelet transform spectral analysis. The T1DM group exhibited disorganized pancreatic microcirculatory oscillation. Glycine supplementation significantly restored regular biorhythmic contraction and relaxation, improving blood distribution patterns. Further-more, glycine reversed the lower amplitudes of endothelial oscillators in T1DM mice. Ultrastructural deterioration of islet microvascular endothelial cells (IMECs) and islet microvascular pericytes, including membrane and organelle damage, collagenous fiber proliferation, and reduced edema, was substantially reversed by glycine supplementation. Additionally, glycine supplementation inhibited the production of IL-6, TNF-α, IFN-γ, pro-MMP-9, and VEGF-A in T1DM, with no significant changes in energetic metabolism observed in glycine-supplemented IMECs. A statistically significant decrease in MDA levels accompanied by an increase in SOD levels was also observed with glycine supplementation. Notably, negative correlations emerged between inflammatory cytokines and microhemodynamic profiles. These findings suggest that glycine supplementation may offer a promising therapeutic approach for protecting against pancreatic microcirculatory dysfunction in T1DM.