A Dietary Pattern with More Fruits and Vegetables in Children of Mothers who Immigrated to the U.S. from Latin America is Associated with Healthful Nutrient Intake and Weight Status.

BACKGROUND: Children from families who immigrated to the U.S. may consume a lower-quality diet compared to their U.S.-born peers. However, specific features of their dietary patterns, which could be a focus for improving diet quality, are not well-studied. OBJECTIVE: To examine dietary patterns that distinguish interpersonal variability in dietary intake and explore the association of dietary patterns with nutrient intake and weight status. DESIGN: This study was a cross-sectional analysis of baseline data from the Live Well randomized controlled trial collected between 2009 - 2010. PARTICIPANTS/SETTING: 313 children (3 - 12 years) whose mothers immigrated to the U.S. from Latin America and resided in Somerville, MA. MAIN OUTCOME MEASURES: dietary patterns (derived using principal component analysis); nutrient intake (derived from dietary data collected using the Block Food Screener); and weight status (categorized using BMI z-score based on measured height and weight) STATISTICAL ANALYSES PERFORMED: Nutrient intake levels were compared across quartiles for dietary patterns using ANCOVA. Multivariable logistic or linear regression models were used to determine the associations between dietary pattern scores and odds of overweight or obesity or BMI z-scores. RESULTS: Two dietary patterns emerged: "fruits and vegetables" (FV) and "meat and sweets" (MS). Highest adherence to the FV pattern was associated with more healthful nutrient intake and lower odds of having overweight or obesity (OR = 0.37, 95%CI = 0.16, 0.98) but not BMI z-score (ß = -0.07, 95%CI = -0.51, 0.36) compared with the lowest adherence. Adherence to the MS pattern was associated with less healthful nutrient intake but not with the odds of experiencing overweight or obesity (OR = 0.48, 95%CI = 0.16, 1.46). CONCLUSIONS: A healthful dietary pattern in children of families who immigrated to the U.S. from Latin America may include a variety of fruits and vegetables. Longitudinal studies should be conducted to further assess the role of dietary intake patterns on health of these children.

High-Acuity Alcohol-Related Complications During the COVID-19 Pandemic.

Importance: Research has demonstrated an association between the COVID-19 pandemic and increased alcohol-related liver disease hospitalizations and deaths. However, trends in alcohol-related complications more broadly are unclear, especially among subgroups disproportionately affected by alcohol use. Objective: To assess trends in people with high-acuity alcohol-related complications admitted to the emergency department, observation unit, or hospital during the COVID-19 pandemic, focusing on demographic differences. Design, Setting, and Participants: This longitudinal interrupted time series cohort study analyzed US national insurance claims data using Optum's deidentified Clinformatics Data Mart database from March 2017 to September 2021, before and after the March 2020 COVID-19 pandemic onset. A rolling cohort of people 15 years and older who had at least 6 months of continuous commercial or Medicare Advantage coverage were included. Subgroups of interest included males and females stratified by age group. Data were analyzed from April 2023 to January 2024. Exposure: COVID-19 pandemic environment from March 2020 to September 2021. Main Outcomes and Measures: Differences between monthly rates vs predicted rates of high-acuity alcohol-related complication episodes, determined using claims-based algorithms and alcohol-specific diagnosis codes. The secondary outcome was the subset of complication episodes due to alcohol-related liver disease. Results: Rates of high-acuity alcohol-related complications were statistically higher than expected in 4 of 18 pandemic months after March 2020 (range of absolute and relative increases: 0.4-0.8 episodes per 100 000 people and 8.3%-19.4%, respectively). Women aged 40 to 64 years experienced statistically significant increases in 10 of 18 pandemic months (range of absolute and relative increases: 1.3-2.1 episodes per 100 000 people and 33.3%-56.0%, respectively). In this same population, rates of complication episodes due to alcohol-related liver disease increased above expected in 16 of 18 pandemic months (range of absolute and relative increases: 0.8-2.1 episodes per 100 000 people and 34.1%-94.7%, respectively). Conclusions and Relevance: In this cohort study of a national, commercially insured population, high-acuity alcohol-related complication episodes increased beyond what was expected in 4 of 18 COVID-19 pandemic months. Women aged 40 to 64 years experienced 33.3% to 56.0% increases in complication episodes in 10 of 18 pandemic months, a pattern associated with large and sustained increases in high-acuity alcohol-related liver disease complications. Findings underscore the need for increased attention to alcohol use disorder risk factors, alcohol use patterns, alcohol-related health effects, and alcohol regulations and policies, especially among women aged 40 to 64 years.

Self-Supported Chiral Dirhodium Organic Frameworks Enables Efficient Asymmetric Cyclopropanation.

The development of heterogeneous chiral dirhodium catalysts for fabricating important bioactive substances and reducing the loss of noble metals has long been of significant interest. However, there still remains formidable synthetic challenges since it requires multiple steps of the synthetic process, and rhodium is easily leached from solid materials during the reaction. Here, we demonstrated a self-supported strategy based on the Suzuki-Miyaura coupling reaction to construct two chiral dirhodium organic frameworks for heterogeneous asymmetric catalysis. The synthetic approach is simple and efficient since it requires only a small number of preparation steps and does not require any catalyst supporting materials. The obtained chiral dirhodium materials can be highly efficient and recyclable heterogeneous catalysts for asymmetric cyclopropanation between diazooxindole and alkenes. Importantly, Rh2-MOCP-2 exhibited almost similar catalytic performance compared to homogeneous catalyst Rh2(S-Br-NTTL)4. The afforded catalytic performance (93.9% yield with 80.9% ee) highly surpasses previous heterogeneous dirhodium catalysts reported to date.

Ultra-processed food consumption and mortality among patients with stages I-III colorectal cancer: a prospective cohort study.

Background: Ultra-processed foods (UPFs) are emerging as a risk factor for colorectal cancer (CRC), yet how post-diagnostic UPF intake may impact CRC prognosis remains unexplored. Methods: Data collected from food frequency questionnaires were used to estimate intakes of total UPFs and UPF subgroups (serving/d) at least 6 months but less than 4 years post-diagnosis among 2498 patients diagnosed with stages I-III CRC within the Nurses' Health Study and Health Professionals Follow-up Study during 1980-2016. Hazard ratios (HR) and 95% confidence intervals (CIs) of all-cause, CRC- and cardiovascular disease (CVD)-specific mortality in association with UPF consumption were estimated using an inverse probability weighted multivariable Cox proportional hazards regression model, adjusted for confounders. Findings: The mean (SD) age of patients at diagnosis was 68.5 (9.4) years. A total of 1661 deaths were documented, including 321 from CRC and 335 from CVD. Compared to those in the lowest quintile (median = 3.6 servings/d), patients in the highest quintile (median = 10 servings/d) of post-diagnostic UPF intake had higher CVD mortality (HR = 1.65, 95% CI = 1.13-2.40) but not CRC or all-cause mortality. Among UPF subgroups, higher consumption of fats/condiments/sauces was associated with a higher risk of CVD-specific mortality (highest vs. lowest quintile of intake, HR = 1.96, 95% CI = 1.41-2.73), and higher intake of ice cream/sherbet was associated with an increased risk of CRC-specific mortality (highest vs. lowest quintile, HR = 1.86, 95% CI: 1.33-2.61). No statistically significant association was found between UPF subgroups and overall mortality. Interpretation: Higher post-diagnostic intake of total UPFs and fats/condiments/sauces in CRC survivors is associated with higher CVD mortality, and higher ice cream/sherbet intake is linked to higher CRC mortality. Funding: US National Institutes of Health and the American Cancer Society.

Emerging Chemistry for Wide-Temperature Sodium-Ion Batteries.

The shortage of resources such as lithium and cobalt has promoted the development of novel battery systems with low cost, abundance, high performance, and efficient environmental adaptability. Due to the abundance and low cost of sodium, sodium-ion battery chemistry has drawn worldwide attention in energy storage systems. It is widely considered that wide-temperature tolerance sodium-ion batteries (WT-SIBs) can be rapidly developed due to their unique electrochemical and chemical properties. However, WT-SIBs, especially for their electrode materials and electrolyte systems, still face various challenges in harsh-temperature conditions. In this review, we focus on the achievements, failure mechanisms, fundamental chemistry, and scientific challenges of WT-SIBs. The insights of their design principles, current research, and safety issues are presented. Moreover, the possible future research directions on the battery materials for WT-SIBs are deeply discussed. Progress toward a comprehensive understanding of the emerging chemistry for WT-SIBs comprehensively discussed in this review will accelerate the practical applications of wide-temperature tolerance rechargeable batteries.

Identification of a novel intronic variant of ATP6V0A2 in a Han-Chinese family with cutis laxa.

BACKGROUND: Cutis laxa is a connective tissue disease caused by abnormal synthesis or secretion of skin elastic fibers, leading to skin flabby and saggy in various body parts. It can be divided into congenital cutis laxa and acquired cutis laxa, and inherited cutis laxa syndromes is more common in clinic. METHODS: In this study, we reported a case of a Han-Chinese male newborn with ATP6V0A2 gene variant leading to cutis laxa. The proband was identified by whole-exome sequencing to determine the novel variant, and their parents were verified by Sanger sequencing. Bioinformatics analysis and minigene assay were used to verify the effect of this variant on splicing function. RESULTS: The main manifestations of the proband are skin laxity, abnormal facial features, and enlargement of the anterior fontanelle. Whole-exome sequencing showed that the newborn carried a non-canonical splicing-site variant c.117 + 5G > T, p. (?) in ATP6V0A2 gene. Sanger sequencing showed that both parents of the proband carried the heterozygous variant. The results of bioinformatics analysis and minigene assay displayed that the variant site affected the splicing function of pre-mRNA of the ATP6V0A2 gene. CONCLUSIONS: In this study, it was identified that ATP6V0A2 gene c. 117 + 5G > T may be the cause of the disease. The non-canonical splicing variants of ATP6V0A2 gene were rarely reported in the past, and this variant expanded the variants spectrum of the gene. The functional study of minigene assay plays a certain role in improving the level of evidence for the pathogenicity of splicing variants, which lays a foundation for prenatal counseling and follow-up gene therapy.

SF3A2 promotes progression and cisplatin resistance in triple-negative breast cancer via alternative splicing of MKRN1.

Triple-negative breast cancer (TNBC) is the deadliest subtype of breast cancer owing to the lack of effective therapeutic targets. Splicing factor 3a subunit 2 (SF3A2), a poorly defined splicing factor, was notably elevated in TNBC tissues and promoted TNBC progression, as confirmed by cell proliferation, colony formation, transwell migration, and invasion assays. Mechanistic investigations revealed that E3 ubiquitin-protein ligase UBR5 promoted the ubiquitination-dependent degradation of SF3A2, which in turn regulated UBR5, thus forming a feedback loop to balance these two oncoproteins. Moreover, SF3A2 accelerated TNBC progression by, at least in part, specifically regulating the alternative splicing of makorin ring finger protein 1 (MKRN1) and promoting the expression of the dominant and oncogenic isoform, MKRN1-T1. Furthermore, SF3A2 participated in the regulation of both extrinsic and intrinsic apoptosis, leading to cisplatin resistance in TNBC cells. Collectively, these findings reveal a previously unknown role of SF3A2 in TNBC progression and cisplatin resistance, highlighting SF3A2 as a potential therapeutic target for patients with TNBC.

Caregiver perceptions of a pediatric produce prescription program during the COVID-19 pandemic.

Introduction: Produce prescription programs are rapidly expanding as a type of Food is Medicine intervention with prospects for mitigating food insecurity and reducing diet-related health disparities. Gaining insight into participant perspectives on program logistics and perceived impacts is crucial to program success and improvements. Methods: Between May and June 2021, we conducted individual and small group interviews with 23 caregivers with children aged 1-5 years who participated in a produce prescription program from 2020 to 2021 in Texas, U.S. They were provided with a gift card to a major national grocery retailer to purchase fresh produce. The card was reloaded $60 monthly for 8 months with automatic roll-over of unused funds to the next month. Participants also received nutrition education in the form of two videos. A deductive analysis approach was employed, and NVivo qualitative data analysis software was used to perform coding and to assist with subsequent analyses. Results: All 23 participants were female, with an average age of 37.5 years, and the majority identified as Hispanic/Latino (83%). About 43% of the families had three or more children. Six themes were generated from interviews. Three of these themes were related to program logistics: (1) ease of program use; (2) participant satisfaction with the incentive; and (3) desire for additional store options. The remaining main themes pertained to program impact: (1) the enhanced ability to purchase produce; (2) the usefulness of the nutrition education; and (3) persistent challenges encountered when preparing the produce for picky eaters and young children. Conclusion: A pediatric produce prescription program was perceived as logistically easy and a helpful source of financial support for accessing fresh produce. Program features such as card-based incentive system and partnership with major grocery retailer were favored by participants. For future program design, it may be beneficial to consider collaborating with multiple grocery outlets and enhancing the intensity and targeting of nutrition education.

Relationship between sarcopenia and fatty liver in middle-aged and elderly patients with type 2 diabetes mellitus.

OBJECTIVE: In this study, we investigated the relationship between sarcopenia and fatty liver in middle-aged and elderly patients diagnosed with type 2 diabetes mellitus (T2DM) to provide a theoretical foundation for the prevention and treatment of sarcopenia. METHODS: A total of 282 patients diagnosed with T2DM aged 50 and older and were admitted to the Endocrinology Department of Xin Medical University First Affiliated Hospital between December 2021 and February 2023, were selected. Body mass index (BMI), and limb and trunk muscle mass of the patients were measured, and data were collected. Patients were grouped based on the sarcopenia diagnostic criteria. All study participants underwent the same physical examinations and laboratory tests. The relationship between the onset of sarcopenia and fatty liver in middle-aged and elderly patients diagnosed with T2DM was then investigated using statistical analysis. RESULTS: Comparing the sarcopenia group to the non-sarcopenia group revealed statistically significant variations in gender, BMI, fatty liver prevalence rate, uric acid (UA), alanine aminotransferase (ALT), blood glucose, blood lipid associated indicators, and limb skeletal muscle content. There were, however, no statistically significant differences in age, disease duration, hypertension, smoking, or alcohol intake. There was a positive correlation between BMI, UA, fasting c-peptide, and Appendicular Skeletal Muscle Index (ASMI). Higher levels of BMI, ASMI, and UA were identified as protective variables against sarcopenia by multifactorial logistic regression analysis. CONCLUSION: Higher levels of BMI, ASMI, and UA can greatly reduce skeletal muscle atrophy in patients with T2DM. Patients with a fatty liver may be less vulnerable to sarcopenia. There is little evidence, however, that a fatty liver works as a preventive factor against sarcopenia.

[Preliminary application of antibiotic bone cement directly inducing skin regeneration technology in repairing of wound in lateral toe flap donor area].

Objective: To investigate the feasibility and effectiveness of antibiotic bone cement directly inducing skin regeneration technology in the repairing of wound in the lateral toe flap donor area. Methods: Between June 2020 and February 2023, antibiotic bone cement directly inducing skin regeneration technology was used to repair lateral toe flap donor area in 10 patients with a total of 11 wounds, including 7 males and 3 females. The patients' age ranged from 21 to 63 years, with an average of 40.6 years. There were 3 cases of the distal segment of the thumb, 2 cases of the distal segment of the index finger, 1 case of the middle segment of the index and middle fingers, 1 case of the distal segment of the middle finger, and 3 cases of the distal segment of the ring finger. The size of the skin defect of the hand ranged from 2.4 cm×1.8 cm to 4.3 cm×3.4 cm. The disease duration ranged from 1 to 15 days, with an average of 6.9 days. The flap donor sites were located at fibular side of the great toe in 5 sites, tibial side of the second toe in 5 sites, and tibial side of the third toe in 1 site. The skin flap donor site wounds could not be directly sutured, with 2 cases having exposed tendons, all of which were covered with antibiotic bone cement. Results: All patients were followed up 6 months to 2 years, with an average of 14.7 months. All the 11 flaps survived and had good appearance. The wound healing time was 40-72 days, with an average of 51.7 days. There was no hypertrophic scar in the donor site, which was similar to the color of the surrounding normal skin; the appearance of the foot was good, and wearing shoes and walking of the donor foot were not affected. Conclusion: It is a feasible method to repair the wound in the lateral foot flap donor area with the antibiotic bone cement directly inducing skin regeneration technology. The wound heals spontaneously, the operation is simple, and there is no second donor site injury.

STING Mediates LPS-induced Acute Lung Injury by Regulating Ferroptosis.

The pathogenesis of acute lung injury is not fully understood. Stimulator of interferon genes (STING) and ferroptosis have been implicated in various pathological and physiological processes, including acute lung injury (ALI). However, the relationship between STING and ferroptosis in lipopolysaccharide (LPS)-induced ALI is unclear. We found that LPS stimulation activated STING and ferroptosis. Furthermore, STING knockout and ferroptosis inhibitor alleviated lung inflammation and epithelial cell damage. Also, STING knockout reduced inflammation injury and ferroptosis. Notably, the ferroptosis inducer reversed the alleviation of inflammation caused by STING knockout. These results show that STING participates in the inflammation injury of ALI by regulating ferroptosis. Results also showed that p-STAT3 levels increased after STING knockout, suggesting that STING negatively regulates STAT3 activation. Besides, STAT3 inhibitor aggravated ferroptosis after STING knockout, indicating that STING regulates ferroptosis through STAT3 signaling. In conclusion, STING mediates LPS-induced ALI by regulating ferroptosis, indicating that STING and ferroptosis may be new targets for ALI treatment.

A bibliometric study on trends in chiropractic research from 1920 to 2023.

OBJECTIVE: An increasing body of evidence suggests a positive role of chiropractic in the treatment of neuro-musculoskeletal disorders. This study aims to explore current research hotspots and trends, providing insights into the broad prospects of this field. METHODS: A bibliometric review was conducted on all chiropractic articles included in the Web of Science Core Collection before December 31, 2023. RESULTS: Over the past century, the volume of research in the field of chiropractic has been fluctuating annually, with four peaks observed in total. The United States, Canada, Australia, and the United Kingdom are leading countries. Chu, Eric Chun-Pu is the author with the most publications, while Bronfort, Gert has the highest total citation count. The University of Southern Denmark has produced the most publications, while Queens University - Canada is the most central institution. The Journal of Manipulative and Physiological Therapeutics is the journal with the most publications and citations, while the Journal of the American Medical Association is the most central journal. The two most-cited articles were both authored by Eisenberg DM. Emerging keywords include "chronic pain" and "skills". The theoretical mechanisms and scientific basis of chiropractic, its clinical practice and safety, education and training, integration with other disciplines, and patient experiences and satisfaction are the frontiers and hotspots of research. CONCLUSION: This study integrates bibliometric analysis to summarize the current state of research and global network centers in the field of chiropractic, further highlighting the hotspots and trends in this field. However, Individual and national rankings should be interpreted with caution due to our focus on Web of Science rather than PubMed.

High-efficiency electrodeposition of magnesium alloy-based anodes for ultra-stable rechargeable magnesium-ion batteries.

Rechargeable magnesium batteries (RMBs) have attracted much attention because of their high theoretical volumetric capacity and high safety. However, the uneven deposition behavior, harmful corrosion reaction and poor stability of magnesium metal anodes have hindered the practical application of RMBs. Herein, we propose a facile alloy electrodeposition method to construct an artificial layer on an Mg anode. Experimental results show that the polarization of the symmetric magnesium alloy-based (Mg-Sn@Mg and Mg-Bi@Mg) cells is significantly reduced (∼0.05 V) at a current density of 0.1 mA cm-2. The symmetric cells using the prepared Mg alloy anodes exhibited lower voltage hysteresis and ultra-stable cycling performance at a higher density of 1.0 mA cm-2 over 700 h. The in situ optical microscopy study clearly demonstrated that the Mg dendrite formation was successfully retarded by the designed Mg-Sn and Mg-Bi alloy artificial protective layer on Mg anodes. The superiority of Mg-Sn@Mg and Mg-Bi@Mg was further confirmed in full cells using Mo6S8 as the cathode. Compared with the Mo6S8//Mg full cell, the Mo6S8//Mg-Sn@Mg and Mo6S8//Mg-Bi@Mg full cells maintained an ultra-stable electrochemical performance even after 5000 cycles. This proof-of-concept provides a novel scope for the artificial coating layers on Mg anodes prepared by alloy electrodeposition and can be extended to other alloy anodes (i.e. Mg-Cu@Mg and so on). This work provides an avenue for the design of practical and high-performance RMBs and beyond.

Engineering Phage Nanocarriers Integrated with Bio-Intelligent Plasmids for Personalized and Tunable Enzyme Delivery to Enhance Chemodynamic Therapy.

Customizable and number-tunable enzyme delivery nanocarriers will be useful in tumor therapy. Herein, a phage vehicle, T4-Lox-DNA-Fe (TLDF), which adeptly modulates enzyme numbers using phage display technology to remodel the tumor microenvironment (TME) is presented. Regarding the demand for lactic acid in tumors, each phage is engineered to display 720 lactate oxidase (Lox), contributing to the depletion of lactic acid to restructure the tumor's energy metabolism. The phage vehicle incorporated dextran iron (Fe) with Fenton reaction capabilities. H2O2 is generated through the Lox catalytic reaction, amplifying the H2O2 supply for dextran iron-based chemodynamic therapy (CDT). Drawing inspiration from the erythropoietin (EPO) biosynthetic process, an EPO enhancer is constructed to impart the EPO-Keap1 plasmid (DNA) with tumor hypoxia-activated functionality, disrupting the redox homeostasis of the TME. Lox consumes local oxygen, and positive feedback between the Lox and the plasmid promotes the expression of kelch ECH Associated Protein 1 (Keap1). Consequently, the downregulation of the antioxidant transcription factor Nrf2, in synergy with CDT, amplifies the oxidative killing effect, leading to tumor suppression of up to 78%. This study seamlessly integrates adaptable T4 phage vehicles with bio-intelligent plasmids, presenting a promising approach for tumor therapy.

Cucurbitacin B induces ferroptosis in oral leukoplakia via the SLC7A11/mitochondrial oxidative stress pathway.

BACKGROUND: Oral leukoplakia (OLK), characterized by abnormal epithelial hyperplasia, is the most common precancerous oral mucosa lesion and is closely related to oxidative stress. Cucurbitacin B (CuB), a tetracyclic triterpenoid molecule derived from plants, has shown promising anti-proliferative and antioxidant effects in preclinical studies. However, whether CuB can play an antiproliferative role in OLK by regulating oxidative stress remains elusive. PURPOSE: To investigate the role of CuB in inhibiting the malignant progression of oral leukoplakia and to further explore its underlying mechanisms of action. METHODS: In vitro, the effect of CuB on the proliferation, migration, apoptosis, and cell cycle of OLK cells DOK was detected. The core genes and key pathways of OLK and CuB were analyzed in the transcriptome database, by using immunofluorescence, qRT-PCR, and Western blot to evaluate the expression levels of the ferroptosis markers ROS, GSH, MDA, Fe2+, and marker genes SLC7A11, GPX4, and FTH1. Immunohistochemistry of human tissue was performed to investigate the expression of the SLC7A11. In vivo, the model of OLK was established in C57BL/6 mice and the biosafety of CuB treatment for OLK was further evaluated. RESULTS: CuB substantially suppressed the proliferation of DOK cells. Bioinformatics analysis showed that the core targets of OLK crossing with CuB include SLC7A11 and that the essential pathways involve ROS and ferroptosis. In vitro experiments indicated that CuB might promote ferroptosis by down-regulating the expression of SLC7A11. We observed a gradual increase in SLC7A11 expression levels during the progression from normal oral mucosa to oral leukoplakia with varying degrees of epithelial dysplasia. In vivo experiments demonstrated that CuB inhibited the malignant progression of OLK by promoting ferroptosis in OLK mice and exhibited a certain level of biosafety. CONCLUSION: This study demonstrated for the first time that CuB could effectively inhibit the malignant progression of OLK by inducing ferroptosis via activating the SLC7A11/ mitochondrial oxidative stress pathway. These findings indicate that CuB could serve as the lead compound for the future development of anti-oral leukoplakia drugs.

Association of State Insulin Out-of-Pocket Caps With Insulin Cost-Sharing and Use Among Commercially Insured Patients With Diabetes : A Pre-Post Study With a Control Group.

BACKGROUND: Twenty-five states have implemented insulin out-of-pocket (OOP) cost caps, but their effectiveness is uncertain. OBJECTIVE: To examine the effect of state insulin OOP caps on insulin use and OOP costs among commercially insured persons with diabetes. DESIGN: Pre-post study with control group. SETTING: Eight states implementing insulin OOP caps of $25 to $30, $50, or $100 in January 2021, and 17 control states. PARTICIPANTS: Commercially insured persons with diabetes and insulin users younger than 65 years. Subgroups of particular interest included members from states with insulin OOP caps of $25 to $30, enrollees with health savings accounts (HSAs) that require high insulin OOP payments, and lower-income members. MEASUREMENTS: Mean monthly 30-day insulin fills and OOP costs. RESULTS: State insulin caps were not associated with changes in insulin use in the overall population (relative change in fills per month, 1.8% [95% CI, -3.2% to 6.9%]). Insulin users in intervention states saw a 17.4% (CI, -23.9% to -10.9%) relative reduction in insulin OOP costs, largely driven by reductions among HSA enrollees; there was no difference in OOP costs among nonaccount plan members. More generous ($25 to $30) state insulin OOP caps were associated with insulin OOP cost reductions of 40.0% (CI, -62.5% to -17.6%), again primarily driven by a larger reduction in the subgroup with HSA plans. LIMITATIONS: Single national insurer; 9-month follow-up. CONCLUSION: Insulin OOP caps were associated with reduced insulin OOP costs but no overall increases in insulin use. A proposed national insulin cap of $35 for commercially insured persons might lead to meaningful insulin OOP savings but have a limited effect on insulin use. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention and National Institute of Diabetes and Digestive and Kidney Diseases.

Origin and significance of leucine-rich glioma-inactivated 1 antibodies in cerebrospinal fluid.

BACKGROUND: Whether antibodies against leucine-rich glioma-inactivated 1 (LGI1-Abs) in cerebrospinal fluid (CSF) are partially transferred from serum and the impact of CSF-LGI1-Ab positivity on clinical features and prognosis are unclear. Therefore, we aim to investigate the differences in serum titers, clinical features, and outcomes between LGI1-Ab CSF-positive and LGI1-Ab CSF-negative patients. METHODS: Retrospective analysis of serum titers and clinical features according to CSF LGI1-Ab status. In addition, univariate and multivariate logistic regression were performed to identify predictors of worse outcomes. RESULTS: A total of 60 patients with anti-LGI1 encephalitis and positive serum LGI1-Abs were identified, of whom 8 (13.3%) patients were excluded due to the absence of CSF LGI1-Ab testing. Among the remaining 52 patients, 33 (63.5%) were positive for LGI1-Abs in CSF. CSF-positive patients were more likely to have high serum titers (≥ 1:100) than CSF-negative patients (p = 0.003), and Spearman's correlation analysis showed a positive correlation between CSF and serum titers in CSF-positive patients (r2 = 0.405, p = 0.019). Psychiatric symptoms and hyponatremia were more frequent in CSF-positive patients (p < 0.05). Both univariate and multivariate logistic regression analyses showed that CSF LGI1-Ab positivity and delayed immunotherapy are independent risk factors for incomplete recovery (modified Rankin Scale (mRS) > 0 at last follow-up). CONCLUSIONS: LGI1-Ab CSF-positive patients have higher serum titers, and their CSF titers are positively correlated with serum titers, indicating a possible peripheral origin of CSF LGI1-Abs. CSF-positive patients more often present with psychiatric symptoms, hyponatremia, and worse outcomes, suggesting more severe neuronal damage.

Visible light-induced metal-free cascade denitrogenative borylation and iodination of nitroarenes.

An efficient method was developed for the one-pot construction of C-B and C-I via visible light-induced transformation of nitroarenes. This protocol relies on the photochemical properties of nitroarenes under visible light, followed by reduction with B2pin2 and diazotization with tBuONO. An array of arylboronates and iodobenzenes were constructed smoothly after excitation with purple LEDs at room temperature. In addition, the synthetic utility of this method was further demonstrated in the late-stage modification of a drug molecule. The advantages of this strategy include metal-free system, mild reaction conditions and acceptable substrate scope.

Effect of Heteroatom Doping on Electrochemical Properties of Olivine LiFePO4 Cathodes for High-Performance Lithium-Ion Batteries.

Lithium iron phosphate (LiFePO4, LFP), an olivine-type cathode material, represents a highly suitable cathode option for lithium-ion batteries that is widely applied in electric vehicles and renewable energy storage systems. This work employed the ball milling technique to synthesize LiFePO4/carbon (LFP/C) composites and investigated the effects of various doping elements, including F, Mn, Nb, and Mg, on the electrochemical behavior of LFP/C composite cathodes. Our comprehensive work indicates that optimized F doping could improve the discharge capacity of the LFP/C composites at high rates, achieving 113.7 mAh g-1 at 10 C. Rational Nb doping boosted the cycling stability and improved the capacity retention rate (above 96.1% after 100 cycles at 0.2 C). The designed Mn doping escalated the discharge capacity of the LFP/C composite under a low temperature of -15 °C (101.2 mAh g-1 at 0.2 C). By optimizing the doping elements and levels, the role of doping as a modification method on the diverse properties of LFP/C cathode materials was effectively explored.

Propofol improves survival in a murine model of sepsis via inhibiting Rab5a-mediated intracellular trafficking of TLR4.

BACKGROUND: Propofol is a widely used anesthetic and sedative, which has been reported to exert an anti-inflammatory effect. TLR4 plays a critical role in coordinating the immuno-inflammatory response during sepsis. Whether propofol can act as an immunomodulator through regulating TLR4 is still unclear. Given its potential as a sepsis therapy, we investigated the mechanisms underlying the immunomodulatory activity of propofol. METHODS: The effects of propofol on TLR4 and Rab5a (a master regulator involved in intracellular trafficking of immune factors) were investigated in macrophage (from Rab5a-/- and WT mice) following treatment with lipopolysaccharide (LPS) or cecal ligation and puncture (CLP) in vitro and in vivo, and peripheral blood monocyte from sepsis patients and healthy volunteers. RESULTS: We showed that propofol reduced membrane TLR4 expression on macrophages in vitro and in vivo. Rab5a participated in TLR4 intracellular trafficking and both Rab5a expression and the interaction between Rab5a and TLR4 were inhibited by propofol. We also showed Rab5a upregulation in peripheral blood monocytes of septic patients, accompanied by increased TLR4 expression on the cell surface. Propofol downregulated the expression of Rab5a and TLR4 in these cells. CONCLUSIONS: We demonstrated that Rab5a regulates intracellular trafficking of TLR4 and that propofol reduces membrane TLR4 expression on macrophages by targeting Rab5a. Our study not only reveals a novel mechanism for the immunomodulatory effect of propofol but also indicates that Rab5a may be a potential therapeutic target against sepsis.