Synergistically improved cardiovascular outcomes in type 2 diabetes mellitus patients with combined treatment of SGLT-2 inhibitors and pioglitazone.

Background: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) have cardiovascular (CV) benefits, particularly in reducing the risk of heart failure (HF). Pioglitazone (Pio) has shown potential in decreasing the risks of recurrent stroke, non-fatal myocardial infarction (MI), and all-cause mortality but increasing risks of HF. Our study aimed to examine the synergistic effects on CV outcomes in patients with type 2 diabetes mellitus (T2DM) who received the combined treatment of SGLT2i and Pio. Materials and methods: A total of 117,850 patients with T2DM and without a history of HF were selected as the observational study cohort from the Chang Gung Research Database (CGRD) in Taiwan between January 1, 2016, and December 31, 2019. The primary composite outcome was 4-point major adverse CV events (4P-MACE), including CV death, non-fatal MI, non-fatal ischemic stroke, and hospitalization for HF. The study was divided into four groups: a combined treatment group in which SGLT2i and Pio were used, two individual groups in which SGLT2i or Pio was used separately, and a reference group (non-study drugs). Results: Combined treatment of SGLT2i and Pio had the lowest risk of 4P-MACE (adjusted hazard ratio [aHR], 0.66; 95% confidence interval [CI], 0.54-0.80) compared with the reference group after a mean follow-up of 2.2 years. There was no significant difference in risks of hospitalization for HF (adjusted subdistribution hazard ratio, 0.73; 95% CI, 0.49-1.07) compared with the reference group. Conclusions: In T2DM patients without HF, the combined treatment with SGLT2i and Pio may synergistically provide CV benefits without increasing risks of HF.

Association between large neutral amino acids and white matter hyperintensities in middle-aged adults at varying metabolic risk.

This investigation delves into the interplay between large neutral amino acids (LNAA) and metabolic syndrome (MetS) in midlife adults, examining their collective influence on brain structure. While LNAA, such as tryptophan and phenylalanine, are known to bolster cognition in youth, these relationships often reverse later in life. Our study hypothesized an earlier reversal of these benefits in middle-aged adults with MetS, potentially signaling premature brain aging. Eighty participants between 40-61 years underwent MetS component quantification, LNAA measurement via high-performance liquid chromatography, and brain imaging to evaluate white matter hyperintensities (WMH) volume and medial temporal lobe (MTL) cortical thickness. Our linear regression analyses, adjusting for sex, age, and education, revealed that phenylalanine levels moderated the relationship between MetS and WMH volume (F(6, 69) = 3.134, p < 0.05, R2 = 0.214), suggesting the brain impact of MetS may be partly due to phenylalanine catabolism byproducts. LNAA metabolites did not significantly modulate the MetS-MTL cortical thickness relationship. These findings suggest that better understanding of the role of phenylalanine in the pathogenesis of cerebrovascular disease in midlife may be essential to developing early interventions to protect cognitive health. Further research is crucial to elucidate the longitudinal influence of LNAA and MetS on brain health, thereby informing strategies to mitigate cognitive decline.

A Real-World Pharmacovigilance Study of the FDA Adverse Event Reporting System Events for Trametinib.

OBJECTIVE: This research investigates adverse drug events (ADEs) linked to trametinib, utilizing data from the FDA Adverse Event Reporting System (FAERS) database, covering the period from Q2 2013 to Q4 2023. METHODS: We gathered data on ADEs associated with trametinib from the second quarter of 2013 to the fourth quarter of 2023. After standardizing the data, we applied various analytical methods to quantify signals, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation for Neural Networks (BCPNN), and multi-item gamma Poisson shrinker (MGPS). RESULTS: In our examination of 2200 ADE reports with trametinib cited as the primary suspect, we identified 191 adverse reaction terms across 23 system organ classifications. The most frequently reported classifications were general disorders and administration site conditions, with 1254 cases (ROR 0.83, PRR 0.85, IC -0.23, EBGM 0.85), followed by neoplasms (benign, malignant, and unspecified, including cysts and polyps) with 802 cases (ROR 3.59, PRR 3.32, IC 1.73, EBGM 3.32), and investigations with 794 cases (ROR 1.74, PRR 1.66, IC 0.73, EBGM 1.66). Notably, this study also uncovered previously unlabeled adverse reactions such as cheilitis, lobular panniculitis, ulcerative keratitis, and stridor. CONCLUSION: While trametinib provides therapeutic advantages, it is associated with several potential adverse reactions. It is crucial for healthcare providers to closely monitor patients for symptoms such as cheilitis, lobular panniculitis, ulcerative keratitis, stridor, and other adverse events (AEs) during treatment.

Interplay of Large Neutral Amino Acids, Metabolic Syndrome, and Apolipoprotein E ε4 on Brain Integrity at Midlife.

INTRODUCTION: Large neutral amino acids (LNAAs) tryptophan and phenylalanine have been implicated in the pathogenesis of neurodegenerative diseases. Given limited research on the effects of LNAA on brain health across different life stages, vascular risk, and genetic backgrounds, our study aimed to explore the interaction of LNAA levels, metabolic syndrome (MetS), and the presence of the apolipoprotein E ε4 (ApoE ε4) allele brain integrity at midlife. METHODS: Sixty-eight adults aged 40-61 underwent a health assessment to calculate the number of MetS components, quantify LNAA, measure white matter hyperintensity (WMH) volume, and genotype ApoE ε4. Multivariate linear regression analyses were performed to test the joint effect of LNAA, MetS, and ApoE ε4 on WMH while adjusting for sex, age, and education. RESULTS: Significant 3-way interactions were observed between serum tryptophan (ß = 0.042, SE = 0.018, p < 0.05) and phenylalanine (ß = 0.044, SE = 0.013, p < 0.01) levels, number of MetS components, and ApoE ε4 alleles status on WMH volume. Neither individual LNAA levels nor MetS components alone predicted WMH volume. CONCLUSIONS: The study highlights significant 3-way interactions between LNAA, MetS, and genetic risk factors in the pathology of WMH, particularly in individuals genetically predisposed to Alzheimer's disease. These interactions suggest differential impacts of LNAA on WMH volume dependent on both genetic and metabolic factors. Results emphasize the need for personalized metabolic and genetic profile assessments in neurodegenerative disease management.

Comprehensive assessment of the impact of intravitreal faricimab on retinal diseases: A systematic review, meta-analysis, and trial sequential analysis.

BACKGROUND: Faricimab stands as the inaugural and sole bispecific antibody approved by the US Food and Drug Administration (FDA) for intravitreal injection. Nonetheless, the efficacy and safety of intravitreal faricimab remained uncertain. OBJECTIVES: The purpose of this study was to evaluate faricimab. METHODS: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (CRD42023398320). Five databases (Pubmed, Embase, Web of science, Cochrane Library, ClinicalTrials gov) were searched. We calculated pooled standard mean difference or odds ratio with 95 % confident interval under a random-effect model or fixed-effect model. Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was employed to ascertain the reliability of the analyses. Trial sequential analysis was performed to gauge the statistical reliability of the data in the cumulative meta-analysis. RESULTS: 8 studies (3975 participants) were included. The use of faricimab was associated with central subfield thickness (CST) change, but no difference was found in other primary efficacy outcomes. Apart from that, a correlation was observed between the use of faricimab and the risk of vitreous floaters. Based on TSA, strong evidence indicates that compared to the control group, faricimab aided in reducing CST but increasing the risk of vitreous floaters. CONCLUSIONS: In this study, a correlation existed between the use of faricimab and a reduction in CST, indicating a superior therapeutic effect. Moreover, participants treated with faricimab demonstrated a higher risk of vitreous floaters. More randomized controlled trials are essential to further explore the efficacy and safety of faricimab.

Enhancement of Docosahexaenoic Acid and Eicosapentaenoic Acid Biosynthesis in Isochrysis galbana by Bacillus jeotgali.

Isochrysis galbana is valuable in aquaculture due to its production of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). However, achieving high yields of polyunsaturated fatty acids (PUFAs) presents challenges, leading to exploration of innovative approaches. This study investigated the influence of Bacillus jeotgali on the growth of I. galbana and its fatty acid composition. Co-culturing I. galbana with B. jeotgali significantly increased chlorophyll a content and cell abundance, particularly at higher bacterial population densities (algae-to-bacteria ratio of 1:10). Physiological and biochemical analyses found elevated soluble protein content in microalgae co-cultured with B. jeotgali, accompanied by decreased superoxide dismutase (SOD) activity. Fatty acid composition analysis demonstrated a distinctive profile in co-cultured I. galbana, characterized by increased PUFAs, especially EPA and DHA. Gene expression analysis indicated an upregulation of desaturase genes (d4FAD, d5FAD, d6FAD, and d8FAD) associated with PUFA synthesis pathway in I. galbana during co-culturing with B. jeotgali. This study advances our understanding of bacteria-microalgae interactions and presents a promising strategy for enhancing the production of DHA and EPA.

Comparative Study on the Effectiveness, Safety, and Economic Costs of Endoscopic Submucosal Dissection for Colorectal Tumors Under Conscious Sedation and General Anesthesia.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a minimally invasive surgical procedure used for en bloc removal of colorectal tumors. Although colorectal ESD is ideally conducted under conscious sedation, it is often performed under general anesthesia because of its complexity and lengthy duration. Currently, there is limited research on colorectal ESD performed under conscious sedation. The purpose of this study was to evaluate the effectiveness, safety, and economic cost of colorectal ESD under conscious sedation compared to general anesthesia. MATERIALS AND METHODS: Retrospective analysis of 301 patients who underwent ESD treatment for colorectal tumors at the Endoscopy Center of Peking University Cancer Hospital from January 2018 to November 2020. Patients were divided into the sedation group (group S, n=88) and the general anesthesia group (group A, n=213) based on the anesthetic method. To balance the confounding factors between the 2 groups, 75 matched pairs were obtained after using propensity score matching (PSM). Intraoperative and postoperative parameters were then compared between the matched groups. RESULTS: After PSM, there was no statistically significant difference between group S and group A in terms of the surgical time, en bloc resection rate, and complete resection rate. There was also no statistically significant difference in the occurrence rates of bleeding, perforation, and post-ESD electrocoagulation syndrome (PEECS) between the 2 groups. However, the length of hospital stay was significantly shorter in group S (1.23±0.89d) than in group A (5.92±3.05d) (P<0.05). The hospitalization costs were also significantly lower in group S (16482.34±13154.32 yuan) compared with group A (34743.74±13779.40 yuan) (P<0.05). CONCLUSIONS: Compared to general anesthesia, performing ESD for colorectal tumors under conscious sedation has equivalent effectiveness and safety while shortening the hospital stay and reducing the economic costs.

Rational Construction of a 3D Self-Supported Electrode Based on ZIF-67 and Amorphous NiCoP for an Enhanced Oxygen Evolution Reaction.

The development of efficient and Earth-abundant electrocatalysts for the oxygen evolution reaction (OER) is an urgent requirement in the field of electrochemical water splitting. The electrocatalytic performance of the OER can be greatly enhanced by the synergistic combination of zeolite imidazolate frameworks (ZIFs) and transition-metal phosphides, both of which individually exhibit promising capabilities in this regard. In this study, a novel amorphous NiCoP deposited on ZIF-67 sheets supported on Ni foam (labeled as NiCoP/ZIF-67/NF) as an OER electrocatalytic material was successfully synthesized using a simple, secure, and time-efficient two-step strategy. The experimental results demonstrate that NiCoP/ZIF-67/NF possesses a large active surface area with abundant active sites. Also, the synergistic effect and interaction between NiCoP and ZIF-67, as well as between Ni and Co within NiCoP, effectively enhance its electrochemical performance under alkaline conditions. Consequently, NiCoP/ZIF-67/NF exhibits outstanding catalytic activity for OER with an overpotential (η) of 175 mV at a current density of 10 mA cm-2 and a long-term stability over 40 h at 20 mA cm-2 in a 1.0 M KOH electrolyte. The corresponding analyses suggest that the real active sites responsible for the OER are identified as NiOOH and CoOOH species within the structure of NiCoP/ZIF-67/NF. Additionally, the catalytic function and stability of ZIF-67 toward the OER under alkaline conditions were also briefly discussed. This work provides a novel catalytic material for the OER along with a facile strategy to fabricate superior, efficient, and noble metal-free catalysts suitable for energy-related applications.

Gut Microbiome and Atherosclerosis: A Mendelian Randomization Study.

Background: According to recent studies, atherosclerosis and gut microbiota are related. Nevertheless, it has been discovered that the gut microbiota varies across studies, with its function still being debated, and such relationships not proven to be causal. Thus, our study aimed to identify the key gut microbiota taxa (GM taxa) at different taxonomic levels, namely, the phylum, class, order, family, and genus, to investigate any potential causal links to atherosclerosis. Methods: We employed summary data from the MiBioGen consortium on the gut microbiota to conduct a sophisticated two-sample Mendelian randomization (MR) analysis. Pertinent information regarding atherosclerosis statistics was acquired from the FinnGen Consortium R8 publication. To assess causality, the utilized principal analytical technique was the inverse variance-weighted (IVW) method. Supplementary to IVW, additional MR methodologies were employed, including weighted median, MR-Egger, weighted methods, and simple mode. Sensitivity analyses involved the application of Cochrane's Q-test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out analysis. Results: Finally, after performing an MR study on the risk of 211 GM taxa on atherosclerosis, we discovered 20 nominal links and one strong causal link. Firmicutes (phylum ID: 1672) (odds ratio (OR) = 0.852 (0.763, 0.950), p = 0.004) continued to be connected with a lower incidence of coronary atherosclerosis, even after Bonferroni correction. Conclusions: Based on the discovered data, it was established that the phylum Firmicutes exhibits a causal relationship with a reduced occurrence of coronary atherosclerosis. This investigation could potentially provide novel insights into therapeutic objectives for atherosclerosis by focusing on the gut microbiota.

C-H Functionalization-Enabled 11-Step Semisynthesis of (-)-Veragranine A and Characterization of Synthetic Analogs in Osteoarthritis-related Pain Treatment.

We report an efficient semisynthesis of the cholestane steroidal alkaloid (-)-veragranine A with a 6/6/6/5/6/6 hexacyclic ring system, eight stereocenters, and a unique C12-C23 linkage. Our synthesis features a Schönecker-Baran C-H oxidation at C12, a Suzuki-Miyaura cross-coupling to form the C12-C23 bond, and a hydrogen atom transfer (HAT)-initiated Minisci C-H cyclization to forge the C20-C22 bond with desired stereochemistry at C20. These enabling transformations significantly enhanced the overall synthetic efficiency and delivered (-)-veragranine A in 11 steps and over 200 mg from cheap and readily available dehydroepiandrosterone. In addition, this approach allowed flexible syntheses of novel synthetic analogs for biological evaluations in sensory neurons in vitro and in an in vivo model of arthritic pain, from which two novel lead compounds were identified for further development.

Copper-Catalyzed Dearomative 1,2-Hydroamination.

Catalytic olefin hydroamination reactions are some of the most atom-economical transformations that bridge readily available starting materials-olefins and high-value-added amines. Despite significant advances in this field over the last two decades, the formal hydroamination of nonactivated aromatic compounds remains an unsolved challenge. Herein, we report the extension of olefin hydroamination to aromatic π-systems by using arenophile-mediated dearomatization and Cu-catalysis to perform 1,2-hydroamination on nonactivated arenes. This strategy was applied to a variety of substituted arenes and heteroarenes to provide general access to structurally complex amines. We conducted DFT calculations to inform mechanistic understanding and rationalize unexpected selectivity trends. Furthermore, we developed a practical, scalable desymmetrization to deliver enantioenriched dearomatized products and enable downstream synthetic applications. We ultimately used this dearomative strategy to efficiently synthesize a collection of densely functionalized small molecules.

Unveiling Low Temperature Assembly of Dense Fe-N4 Active Sites via Hydrogenation in Advanced Oxygen Reduction Catalysts.

The single-atom Fe-N-C is a prominent material with exceptional reactivity in areas of sustainable energy and catalysis research. It is challenging to obtain the dense Fe-N4 site without the Fe nanoparticles (NPs) sintering during the Fe-N-C synthesis via high-temperature pyrolysis. Thus, a novel approach is devised for the Fe-N-C synthesis at low temperatures. Taking FeCl2 as Fe source, a hydrogen environment can facilitate oxygen removal and dichlorination processes in the synthesis, efficiently favouring Fe-N4 site formation without Fe NPs clustering at as low as 360 °C. We shed light on the reaction mechanism about hydrogen promoting Fe-N4 formation in the synthesis. By adjusting the temperature and duration, the Fe-N4 structural evolution and site density can be precisely tuned to directly influence the catalytic behaviour of the Fe-N-C material. The FeNC-H2-360 catalyst demonstrates a remarkable Fe dispersion (8.3 wt %) and superior acid ORR activity with a half-wave potential of 0.85 V and a peak power density of 1.21 W cm-2 in fuel cell. This method also generally facilitates the synthesis of various high-performance M-N-C materials (M=Fe, Co, Mn, Ni, Zn, Ru) with elevated single-atom loadings.

Large Neutral Amino Acids Moderate the Effects of Metabolic Syndrome on Cognitive Performance in Middle-Aged Adults.

INTRODUCTION: Two large neutral amino acids (LNAA), tryptophan and tyrosine, are precursors to cerebral neurotransmitters and are involved in cognitive function. Higher levels of LNAA in young adults are associated with improved cognition, although these associations appear to reverse over time. Given that exposure to metabolic syndrome (MetS) may induce premature cognitive aging, the current project aims to fill the gap in the literature by examining the effect of LNAA on cognitive performance in midlife adults with metabolic risks. METHODS: Eighty-eight adults, ages 40-61 years, participated in this cross-sectional study. LNAA metabolites were quantified, MetS components were measured using high-performance liquid chromatography, and MetS components were assessed in the laboratory. Composite verbal memory and executive functioning scores were computed using principal component analysis. We used linear regression models to test the interaction between LNAA and MetS while covarying for sex, age, and education. RESULTS: The kynurenine/tryptophan ratio moderated the relation between MetS and verbal memory, even after adjusting for relevant covariates. Tyrosine metabolites were not significant moderators of the association between MetS and executive functioning. CONCLUSION: Our findings suggest that the detected weaker memory performance in adults with a high number of MetS components may be related to relative tryptophan depletion and possible decreases in serotonin production. Further investigation is warranted to examine the potential role of LNAA in associations between cognitive performance and metabolic risks over time.

Valorization of Nannochloropsis oceanica for integrated co-production of violaxanthin cycle carotenoids.

The development of integrated co-production of multiple high-purity carotenoids from microalgal cells holds considerable significance for the valorization of microalgae. In this study, the economical microalga Nannochloropsis oceanica was identified as an accumulator of violaxanthin cycle carotenoids, including violaxanthin, antheraxanthin, and zeaxanthin. Notably, a novel and competent approach for the integrated co-production of violaxanthin cycle carotenoids was explored, encompassing four steps: microalgal cultivation, solvent extraction, octadecylsilyl open-column chromatography, and ethanol precipitation. Under optimal co-production conditions, the purities of the obtained violaxanthin, antheraxanthin, and zeaxanthin all exceeded 92%, with total recovery rates of approximately 51%, 40%, and 60%, respectively. Utilizing nuclear magnetic resonance techniques, the purified violaxanthin, antheraxanthin, and zeaxanthin were identified as all-trans-violaxanthin, all-trans-antheraxanthin, and all-trans-zeaxanthin, respectively. This method held significance for the multiproduct biorefinery of the microalga N. oceanica and carried potential future implications for the violaxanthin cycle carotenoids.

Tanshinone I Stimulates Pyroptosis of Cisplatin-Resistant Gastric Cancer Cells by Activating the NF-κB/Caspase-3(8)/GSDME Signaling Pathway.

Cisplatin (DDP) resistance frequently occurs in gastric cancer (GC) therapy. Tanshinone I is a liposoluble phenanthraquinone compound present in the roots of Salvia miltiorrhiza Bunge (Danshen). In this study, we aimed to explore the effects of tanshinone I on modulating DDP resistance of GC cells in vitro and in vivo. DDP-resistant GC cell models (BGC823/DDP and SGC7901/DDP) were established, and their viability, proliferation, migration, lactate dehydrogenase activity, reactive oxygen species (ROS) generation, and pyroptosis were assessed after DDP treatment with or without tanshinone I. In addition, a mouse model with subcutaneously transplanted GC tumors was established to confirm the effects of tanshinone I and DDP on tumor growth and cell pyroptosis. The results revealed that tanshinone I inhibited DDP-resistant GC cell proliferation and migration; increased intracellular ROS levels; and activated cell pyroptosis by enhancing the levels of cleaved caspase-8, cleaved caspase-3, GSDME-NT, phospho-IKK-α/ß, and nuclear factor kappa-B (NF-κB). GSDME knockdown weakened these effects of tanshinone I on DDP-resistant GC cells. Furthermore, DDP combined with tanshinone I inhibited the growth of subcutaneously transplanted GC tumors in mice by reducing cell proliferation and inducing pyroptosis. In conclusion, tanshinone I reversed DDP resistance of GC cells by stimulating pyroptosis, by activating NF-κB/caspase-3(8)/GSDME signaling pathway.

Doping Ru on FeNi LDH/FeII/III-MOF heterogeneous core-shell structure for efficient oxygen evolution.

Noble metal-based catalysts such as RuO2 and IrO2 are widely used in the catalysis of the OER. However, because of their high price and poor stability, it is urgent to develop transition metal-based electrocatalysts with low precious metal doping as an alternative. Layered double hydroxides (LDHs) grown on 3D metal-organic frameworks (MOFs) are ideal for doping precious metals owing to abundant defects at the heterointerface, large surface area, and intrinsic oxygen evolution activity. In this study, a novel FeNi LDH/MOF heterostructure was prepared via a two-step solvothermal method using Fe-soc-MOFs as the substrate. Subsequently, Ru was introduced through a hydrothermal process. The as-synthesized Ru@FeNi LDH/MOF has an overpotential of only 242 mV at a current density of 10 mA cm-2 and can be used in continuous electrolysis for 48 h. Its unique nanocubic core-shell structure and flower-like LDHs on its surface provide a large number of active sites, which become the key to ensuring high activity and stability. With the doping of Ru, the electronic structure was adjusted and electron transfer was accelerated, further improving electrochemical activity. This study provides a new idea for developing transition metal-based catalysts with low noble metal loading.

Ultralong Cycling and Safe Lithium-Sulfur Pouch Cells for Sustainable Energy Storage.

While layered metal oxides remain the dominant cathode materials for the state-of-the-art lithium-ion batteries, conversion-type cathodes such as sulfur present unique opportunities in developing cheaper, safer, and more energy-dense next-generation battery technologies. There has been remarkable progress in advancing the laboratory scale lithium-sulfur (Li-S) coin cells to a high level of performance. However, the relevant strategies cannot be readily translated to practical cell formats such as pouch cells and even battery pack. Here these key technical challenges are addressed by molecular engineering of the Li metal for hydrophobicization, fluorination and thus favorable anode chemistry. The introduced tris(2,4-di-tert-butylphenyl) phosphite (TBP) and tetrabutylammonium fluoride (TBA+F-) as well as cellulose membrane by rolling enables the formation of a functional thin layer that eliminates the vulnerability of Li metal towards the already demanding environment required (1.55% relative humidity) for cell production and gives rise to LiF-rich solid electrolyte interphase (SEI) to suppress dendrite growth. As a result, Li-S pouch cells assembled at a pilot production line survive 400 full charge/discharge cycles with an average Coulombic efficiency of 99.55% and impressive rate performance of 1.5 C. A cell-level energy density of 417 Wh kg-1 and power density of 2766 W kg-1 are also delivered via multilayer Li-S pouch cell. The Li-S battery pack can even power an unmanned aerial vehicle of 3 kg for a fairly long flight time. This work represents a big step forward acceleration in Li-S battery marketization for future energy storage featuring improved safety, sustainability, higher energy density as well as reduced cost.

Fe-Based Metal Organic Framework-Derived FeNiP/N-Doped Carbon Heterogeneous Core-Shell Structures for Oxygen Evolution.

It is of great significance to explore high activity, low overpotential, and outstanding durability electrocatalysts without precious metals for oxygen evolution reaction to reduce the energy consumption in the electrolysis of water to product hydrogen. Metal organic frameworks (MOFs) with periodic structure and uniform pore distribution have been widely used as precursors for the synthesis of transition metal electrocatalysts. Herein, we first synthesized nanoscale Fe-soc-MOFs with relatively high specific surface area and in situ converted it into nickel-iron double layer hydroxide/MOF (FeNi LDH/MOF) by Ni2+ etching. Finally, a nickel-iron phosphide/nitrogen-doped carbon cubic nanocage (FeNiP/NC) was obtained by calcination and phosphating. FeNiP/NC with its unique core-shell structure has an overpotential of only 240 mV at a current density of 10 mA/cm2 and can be continuously electrolyzed for 45 h. High catalytic activity of FeNiP/NC is mainly attributed to the action of Fe and Ni bimetals and the synergistic effect between FeNiP and N-doped porous carbon, which was confirmed by the calculation of density functional theory (i.e., Gibbs free energy). After a long period of electrolysis, FeNiP was converted to MOOH (M = Fe and Ni) and became the new active site. This study provides a feasible optimization strategy for the development of high-efficiency three-dimensional electrode materials without precious metals.

Novel and Advanced Ultrasound Techniques for Thyroid Thermal Ablation.

Thyroid radiofrequency ablation and microwave ablation are widely adopted minimally invasive treatments for diverse thyroid conditions worldwide. Fundamental skills such as the trans-isthmic approach and the moving shot technique are crucial for performing thyroid ablation, and advanced techniques, including hydrodissection and vascular ablation, improve safety and efficacy and reduce complications. Given the learning curve associated with ultrasound-guided therapeutic procedures, operators need training and experience. While training models exist, limited attention has been given to ultrasound maneuvers in ablation needle manipulation. This article introduces two essential maneuvers, the zigzag moving technique and the alienate maneuver, while also reviewing the latest ultrasound techniques in thyroid ablation, contributing valuable insights into this evolving field.

Association between Large Neutral Amino Acids and Brain Integrity in Middle-Aged Adults at Metabolic Risk.

This investigation delves into the interplay between large neutral amino acids (LNAA) and metabolic syndrome (MetS) in midlife adults, examining their collective influence on brain structure and cognitive function. While LNAA, such as tryptophan and phenylalanine, are known to bolster cognition in youth, our study hypothesizes a reversal of these benefits in older adults with MetS, potentially signaling premature cognitive aging. Eighty participants between 40-61 years underwent MetS component quantification, LNAA measurement via high-performance liquid chromatography, and brain imaging to evaluate white matter hyperintensity (WMH) volume and medial temporal lobe (MTL) cortical thickness. Our linear regression analysis, adjusting for sex, age, and education, revealed that phenylalanine levels moderated the relationship between MetS and WMH volume (F(6, 69) = 3.134, p < 0.05, R2 = 0.214), suggesting that MetS's cognitive impact may be partly due to phenylalanine catabolism byproducts. However, LNAA metabolites did not significantly modulate the MetS-MTL cortical thickness relationship. The findings suggest that LNAA metabolic dysregulation, marked by elevated levels in the presence of MetS, could correlate with brain structural compromises, particularly in the form of MTL cortical thinning and increased WMH load, detectable in midlife. This nuanced understanding of LNAA's role in cognitive health amid cardiovascular risk factors is pivotal, proposing a potential biomarker for early intervention. Further research is crucial to elucidate the longitudinal influence of LNAA and MetS on brain health, thereby informing strategies to mitigate cognitive decline.