Unraveling the Complexity of Parkinson's Disease: Insights into Pathogenesis and Precision Interventions.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic neuron loss, leading to motor and non-motor symptoms. Early detection before symptom onset is crucial but challenging. This study presents a framework integrating circuit modeling, non-equilibrium dynamics, and optimization to understand PD pathogenesis and enable precision interventions. Neuronal firing patterns, particularly oscillatory activity, play a critical role in PD pathology. The basal ganglia network, specifically the subthalamic nucleus-external globus pallidus (STN-GPe) circuitry, exhibits abnormal activity associated with motor dysfunction. The framework leverages the non-equilibrium landscape and flux theory to identify key connections generating pathological activity, providing insights into disease progression and potential intervention points. The intricate STN-GPe interplay is highlighted, shedding light on compensatory mechanisms within this circuitry may initially counteract changes but later contribute to pathological alterations as disease progresses. The framework addresses the need for comprehensive evaluation methods to assess intervention outcomes. Cross-correlations between state variables provide superior early warning signals compared to traditional indicators relying on critical slowing down. By elucidating compensatory mechanisms and circuit dynamics, the framework contributes to improved management, early detection, risk assessment, and potential prevention/delay of PD development. This pioneering research paves the way for precision medicine in neurodegenerative disorders.

Barriers and facilitators of the nurse providing evidence-based preoperative visit-care for transcatheter aortic valve replacement: a mixed-methods study based on an evidence application setting.

BACKGROUND: Preoperative visit-care for transcatheter aortic valve replacement (TAVR) plays a crucial role in improving the quality of care and patient safety. However, preoperative care for TAVR patients is still in its early stages in China, with the care often being experience-based. The application of relevant evidence in nursing practice is necessary. Little is known regarding the facilitators and barriers to apply and compliance to the evidences about preoperative visit-care for TAVR in nursing. METHODS: The Nurse's Compliance Checklist was used to investigate the evidence-based compliance of nurses (n = 21) who worked in the TAVR team in the evidence-based implementation setting. Meanwhile, an Evidence-Based Practice Beliefs Scale, and Influencing Factors Checklist were used to investigate all nurses (n = 66) who work in the same setting. Stakeholders (Middle and senior-level nursing administrators, frontline clinical nurses, and patients) interview was carried out to further disclose the barriers and facilitators in the process of evidence-based practice. RESULTS: The results of this study showed that only 1 evidence implemented fully (100%) by nurses, 3 evidences with 0% implementation rate, and implementation rate of the other evidences were 9.5∼71.4%. The overall score of nurses' evidence-based nursing belief level was (3.52 ± 0.82). Three domains of barriers were identified: the Context Domain included lack of nursing procedures, inadequate health education materials, insufficient training; the Practitioner Domain included insufficient attention, lack of relevant knowledge, high work pressure and uncertainty of expected results, and Patient Domain included lack of relational knowledge. Facilitating factors included leadership support, nurse' high evidence-based nursing belief, high executive ability and enthusiasm for learning. CONCLUSION: The study indicated that the nurses' compliance of evidence-based practice in preoperative visit-care for TAVR was in lower level. There were some factors influencing the application of the evidences. The study revealed potential modifiable barriers to the successful implementation of evidence-based preoperative visit-care, including a lack of preoperative visit- care routine, related knowledge and training. Leadership support and nurse training should be considered to improve nurses' compliance with evidence-based practice.

Effect of Deep Brain Stimulation on Comorbid Self-injurious Behavior: A Systematic Review and Meta-analysis of Individual Patient Data.

OBJECTIVE: Self-injurious behavior (SIB) can occur in the setting of many neurologic disorders that are amenable to deep brain stimulation (DBS). Although certain brain targets are believed to be particularly effective for SIB, improvements in the primary neurologic condition may also reduce co-occurring SIB. We performed a systematic review and meta-analysis of individual participant data to characterize the effects of DBS across various neurologic disorders and brain targets on comorbid SIB. MATERIALS AND METHODS: A systematic review of all available literature on DBS in treating disorders with co-occurring SIB was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Individual participant data were extracted and standardized mean differences (SMDs) in metrics of SIB severity and/or frequency were calculated for meta-analysis. Demographic variables and adverse events were also collated. RESULTS: Data from 59 patients, identified from 24 articles, with comorbid SIB who underwent DBS for various indications were extracted. The primary neurologic diagnoses included Tourette syndrome (n = 40), dystonia (n = 7), epilepsy (n = 5), acquired brain injury (n = 3), dyskinesia (n = 2), and obsessive-compulsive disorder (n = 2). Overall, DBS was highly effective in treating comorbid SIB (Mean SMD = -2.4, p < 0.0001) across primary disorders and intracranial targets. Patients with dystonia and DBS targeting the posterior hypothalamus had relatively less success at mitigating comorbid SIB. CONCLUSIONS: In patients with comorbid SIB, DBS to treat the primary neurologic condition may also mitigate SIB. Although several targets are emerging for the treatment of severe SIB, this work suggests that DBS targeting the primary neurologic condition should be first considered in comorbid SIB.

Emerging trends and research hotspots in the relationship between mast cells and atopic dermatitis based on the literature from 2001 to 2024: A bibliometric and visualized analysis.

BACKGROUND: Atopic dermatitis (AD) is a prevalent chronic inflammatory and highly pruritic skin condition characterized by the infiltration of immune cells, notably eosinophils and mast cells. Mast cells (MCs) critically participate in the complex pathogenesis of AD through multiple pathways and have recently garnered growing attention in research. Despite the abundance of related studies published over the years, a comprehensive bibliometric analysis on this topic remains lacking. OBJECTIVE: Our objective was to perform an up-to-date bibliometric analysis of the literature focusing on the relationship between MCs and AD. This analysis would provide valuable insights through a thorough bibliometric review, enabling a clearer understanding of the current research landscape, pinpointing key studies, and detecting emerging trends within this field. METHODS: We searched the Web of Science Core Collection (WoSCC) database on 15 July 2024. The data retrieval strategy was structured as follows: #1: TS = ("mast cells") OR TS = ("mast cell") OR TS = ("mastocyte"); #2: TS = ("atopic dermatitis") OR TS = ("atopic eczema") Final data: (#1 AND #2). A total of 2272 items published between 2001 and 2024 were included. Several scientometric visualization tools, including VOSviewer, R-bibliometrix, CiteSpace and an online analytical platform, were utilized to conduct text mining and to visualize the bibliometric data, facilitating a comprehensive analysis of research trends and patterns. RESULTS: Out of the initial 2272 articles retrieved, 2168 were selected for analysis after applying inclusion and exclusion criteria based on publication type. The findings indicate a steady and substantial exponential growth in the annual number of publications focused on the relationship between over the years. The South Korea (547/2168), USA (465/2168) and Japan (436/2168) were the major contributors within this field, collectively constituting more than half of the total publications. To clarify the underlying mechanisms and role of MCs in the pathogenesis of AD and to make MCs prime targets for therapeutic intervention have garnered the most attention in this field. According to references analysis, the research emphasis has shifted to developing MC-related therapeutics and intervention and regulating the immune system of AD patients through modulating the activity of various immune cells. On the basis of keywords analysis, we outlined the following research frontiers and hotpots in the future: the role of oxidative stress in the pathogenesis; imbalance in the different types of T helper (Th) cells during immune response; skin barrier and barrier dysfunction; improving quality of life; sensory neurons; biological agents and small-molecule drugs. Furthermore, IL-13, IL-4, NFKB1, BCGF-1 and CD4 ranked as the top five genes that have received the most investigative attention in the intersection of MCs and AD. CONCLUSION: In a word, this analysis would greatly benefit from a thorough bibliometric review to gain a deeper understanding of the current research landscape, identify pivotal studies and pinpoint emerging trends in the field of MCs and AD. Meanwhile, our findings offered researchers a holistic perspective of ongoing developments, serving as a valuable resource for guiding future research and informing decision-making for both researchers and policymakers in this area.

Broad Adaptability of Coronavirus Adhesion Revealed from the Complementary Surface Affinity of Membrane and Spikes.

Coronavirus stands for a large family of viruses characterized by protruding spikes surrounding a lipidic membrane adorned with proteins. The present study explores the adhesion of transmissible gastroenteritis coronavirus (TGEV) particles on a variety of reference solid surfaces that emulate typical virus-surface interactions. Atomic force microscopy informs about trapping effectivity and the shape of the virus envelope on each surface, revealing that the deformation of TGEV particles spans from 20% to 50% in diameter. Given this large deformation range, experimental Langmuir isotherms convey an unexpectedly moderate variation in the adsorption-free energy, indicating a viral adhesion adaptability which goes beyond the membrane. The combination of an extended Helfrich theory and coarse-grained simulations reveals that, in fact, the envelope and the spikes present complementary adsorption affinities. While strong membrane-surface interaction lead to highly deformed TGEV particles, surfaces with strong spike attraction yield smaller deformations with similar or even larger adsorption-free energies.

Two-Dimensional Semiconductors for State-of-the-Art Complementary Field-Effect Transistors and Integrated Circuits.

As the trajectory of transistor scaling defined by Moore's law encounters challenges, the paradigm of ever-evolving integrated circuit technology shifts to explore unconventional materials and architectures to sustain progress. Two-dimensional (2D) semiconductors, characterized by their atomic-scale thickness and exceptional electronic properties, have emerged as a beacon of promise in this quest for the continued advancement of field-effect transistor (FET) technology. The energy-efficient complementary circuit integration necessitates strategic engineering of both n-channel and p-channel 2D FETs to achieve symmetrical high performance. This intricate process mandates the realization of demanding device characteristics, including low contact resistance, precisely controlled doping schemes, high mobility, and seamless incorporation of high- κ dielectrics. Furthermore, the uniform growth of wafer-scale 2D film is imperative to mitigate defect density, minimize device-to-device variation, and establish pristine interfaces within the integrated circuits. This review examines the latest breakthroughs with a focus on the preparation of 2D channel materials and device engineering in advanced FET structures. It also extensively summarizes critical aspects such as the scalability and compatibility of 2D FET devices with existing manufacturing technologies, elucidating the synergistic relationships crucial for realizing efficient and high-performance 2D FETs. These findings extend to potential integrated circuit applications in diverse functionalities.

Upregulation of phosphodiesterase 7A leads to the downregulation of cAMP-PKA-CREB-BDNF signaling and neuroinflammation in the hippocampus and contributes to concurrent chronic pain and depression in two mouse models.

BACKGROUND: Phosphodiesterases (PDEs) are enzymes that catalyze the hydrolysis of cyclic adenosine monophosphate AMP (cAMP) and/or cyclic guanosine monophosphate (cGMP). PDE inhibitors can mitigate chronic pain and depression when these disorders occur individually; however, there is limited understanding of their role in concurrent chronic pain and depression. We aimed to evaluate the mechanisms of action of PDE using two mouse models of concurrent chronic pain and depression. METHODS: C57BL/6J mice were subjected to partial sciatic nerve ligation (PSNL) to induce chronic neuropathic pain or injected with complete Freund's adjuvant (CFA) to induce inflammatory pain, and both animals showed depression-like behavior. First, we determined the change in PDE expression in both animal models. Next, we determined the effect of PDE7 inhibitor BRL50481 or hippocampal PDE7A knockdown on PSNL- or CFA-induced chronic pain and depression-like behavior. We also investigated the role of cAMP-protein kinase A (PKA)-cAMP response element binding protein (CREB)-brain-derived neurotrophic factor (BDNF) signaling and neuroinflammation in the effect of PDE7A inhibition on PSNL- or CFA-induced chronic pain and depression-like behavior. RESULTS: This induction of chronic pain and depression in the two animal models upregulated hippocampal PDE7A. Oral administration of PDE7 inhibitor, BRL50481, or hippocampal PDE7A knockdown significantly reduced mechanical hypersensitivity and depression-like behavior. Hippocampal PDE7 inhibition reversed PSNL- or CFA-induced downregulation of cAMP and BDNF and the phosphorylation of PKA, CREB and p65. cAMP agonist forskolin, reversed these changes and caused milder behavioral symptoms of pain and depression. BRL50481 reversed neuroinflammation in the hippocampus in PSNL mice. CONCLUSIONS: Hippocampal PDE7A mediated concurrent chronic pain and depression in both mouse models by inhibiting cAMP-PKA-CREB-BDNF signaling Inhibiting PDE7A or activating cAMP-PKA-CREB-BDNF signaling are potential strategies to treat concurrent chronic pain and depression.

Oncocytic cell carcinoma of the thyroid with TERT promoter mutation presenting as asphyxia in an elderly: a case report.

Introduction: The prevalence of thyroid nodules and malignancies in the elderly is a growing concern. Thyroid nodules in this population have unique characteristics, requiring careful treatment strategies that balance risks and benefits. Oncocytic carcinoma of the thyroid (OCA) is a rare, aggressive subtype with diagnostic challenges. Methods: This case features an 84-year-old patient who presented with a neck mass and symptoms of asphyxia. Clinical evaluation, imaging studies, and biopsy were conducted to assess the nature of the thyroid lesion. Molecular testing, including genetic analysis, was performed to identify specific mutations associated with OCA and guide treatment decisions. Results: The patient was diagnosed with oncocytic carcinoma of the thyroid. The molecular testing revealed specific genetic mutations indicative of OCA, confirming the diagnosis. The presence of these mutations guided the treatment plan, emphasizing the importance of molecular diagnostics in managing thyroid malignancies, especially in the elderly. Discussion: This case illustrates the complexities of diagnosing and treating thyroid malignancies in the elderly. Biopsy and molecular testing provided diagnostic accuracy and informed treatment. Individualized approaches are essential for better outcomes, especially in aggressive subtypes, balancing the risks and benefits of intervention.

Electrostatic microfiltration (EM) enriches and recovers viable microorganisms at low-abundance in large-volume samples and enhances downstream detection.

Rapid and sensitive detection of pathogens in various samples is crucial for disease diagnosis, environmental surveillance, as well as food and water safety monitoring. However, the low abundance of pathogens (<10 CFU) in large volume (1 mL-1 L) samples containing vast backgrounds critically limits the sensitivity of even the most advanced techniques, such as digital PCR. Therefore, there is a critical need for sample preparation that can enrich low-abundance pathogens from complex and large-volume samples. This study develops an efficient electrostatic microfiltration (EM)-based sample preparation technique capable of processing ultra-large-volume (≥500 mL) samples at high throughput (≥10 mL min-1). This approach achieves a significant enrichment (>8000×) of extremely-low-abundance pathogens (down to level of 0.02 CFU mL-1, i.e., 10 CFU in 500 mL). Furthermore, EM-enabled sample preparation facilitates digital amplification techniques sensitively detecting broad pathogens, including bacteria, fungi, and viruses from various samples, in a rapid (≤3 h) sample-to-result workflow. Notably, the operational ease, portability, and compatibility/integrability with various downstream detection platforms highlight its great potential for widespread applications across diverse settings.

InP/LiNbO3 Covalent Heterointerface Construction via an Asymmetric Plasma Activation Strategy for Hybrid Integrated Quantum Systems.

Lithium niobate (LiNbO3) is emerging as an appealing candidate for integrated optical applications with enhanced complexity, owing to its inherent abundant optoelectronic properties. To compensate for the inability of LiNbO3 to generate indistinguishable single photons, the evanescent coupling heterointerface constructed between III-V compound semiconductors (e.g., InP) and LiNbO3 through plasma activation provides a feasible solution for balancing the integration efficiency and interfacial stability while achieving sub-50 nm alignment accuracy between devices, thus offering ultracompact on-chip light sources for classical optoelectronics and quantum optics. However, a challenge remains in the formation of the InP/LiNbO3 platform due to the huge mismatch in the coefficient of thermal expansion. Here, we demonstrate the InP/LiNbO3 covalent heterointerface using an asymmetric plasma activation strategy. Different plasmas are used for the activation of InP and LiNbO3 specifically, balancing the enhancement of surface functional group density with the avoidance of defect generation effectively. More importantly, combined with surface comprehensive characterizations and interface performance, we determine that the introduction of ammonia solution enables the surface hydroxyl groups to be "effective" as LiNbO3 surface relaxation increases the chance of -OH groups' contact. Therefore, a robust covalent bond network is established across the InP/LiNbO3 interface at 80 °C with an enhanced bonding strength of 9.7 MPa. Moreover, a hybrid quantum photonic chip based on the InP/LiNbO3 platform is designed to compute the coupling efficiency and the impact of misalignment on it, demonstrating the potential of extending the platform to hybrid integrated quantum systems.

Ribosomal modification protein rimK-like family member A activates betaine-homocysteine S-methyltransferase 1 to ameliorate hepatic steatosis.

Nonalcoholic fatty liver disease (NAFLD) is a serious threat to public health, but its underlying mechanism remains poorly understood. In screening important genes using Gene Importance Calculator (GIC) we developed previously, ribosomal modification protein rimK-like family member A (RIMKLA) was predicted as one essential gene but its functions remained largely unknown. The current study determined the roles of RIMKLA in regulating glucose and lipid metabolism. RIMKLA expression was reduced in livers of human and mouse with NAFLD. Hepatic RIMKLA overexpression ameliorated steatosis and hyperglycemia in obese mice. Hepatocyte-specific RIMKLA knockout aggravated high-fat diet (HFD)-induced dysregulated glucose/lipid metabolism in mice. Mechanistically, RIMKLA is a new protein kinase that phosphorylates betaine-homocysteine S-methyltransferase 1 (BHMT1) at threonine 45 (Thr45) site. Upon phosphorylation at Thr45 and activation, BHMT1 eliminated homocysteine (Hcy) to inhibit the activity of transcription factor activator protein 1 (AP1) and its induction on fatty acid synthase (FASn) and cluster of differentiation 36 (CD36) gene transcriptions, concurrently repressing lipid synthesis and uptake in hepatocytes. Thr45 to alanine (T45A) mutation inactivated BHMT1 to abolish RIMKLA's repression on Hcy level, AP1 activity, FASn/CD36 expressions, and lipid deposition. BHMT1 overexpression rescued the dysregulated lipid metabolism in RIMKLA-deficient hepatocytes. In summary, RIMKLA is a novel protein kinase that phosphorylates BHMT1 at Thr45 to repress lipid synthesis and uptake. Under obese condition, inhibition of RIMKLA impairs BHMT1 activity to promote hepatic lipid deposition.

Cost-Effectiveness of Varicella Vaccination for 1-4-Year-Olds in Shanghai, China.

INTRODUCTION: Varicella has not yet been included in the National Immunization Program (NIP) in China, and varicella vaccination strategies vary by region. To determine the optimal varicella vaccination strategy in Shanghai, China, the cost-effectiveness and 5-year costs of 5 immunization scenarios were analyzed. METHODS: A static decision tree-Markov model was developed in 2022 to assess the cost-effectiveness and 5-year costs of voluntary and routine varicella vaccination programs in the 2019 birth cohort in Shanghai from a societal perspective. Parameters were collected in 2022 from the varicella surveillance system, a questionnaire survey of 414 guardians of patients with childhood varicella, and semi-structured interviews with 20 experts on varicella outbreaks from different institutions in Shanghai. The outcomes included varicella cases avoided, quality-adjusted life year (QALY) loss, and incremental costs per QALY (ICER). The 5-year costs were compared with local medical expenditures. RESULTS: Among the 5 scenarios, one dose of routine varicella vaccination was the most cost-saving (USD 70.2) and cost-effective (Dominant) with a 5-year immunization expenditure of USD 9.9 million. Two doses of routine varicella vaccination had the highest QALY (29.9), and its ICER (USD 791.9/QALY) was below the willingness-to-pay threshold (USD 5,203-23,767/QALY). The 5-year immunization expenditure was USD 19.8 million. The effectiveness and price of vaccines, vaccination coverage, and per capita income are the 4 main factors that affect ICERs. CONCLUSIONS: In Shanghai, the 2 doses of routine varicella vaccination strategy for 1- and 4-year-olds with a 95% coverage rate was found to be the optimal varicella immunization strategy.

Viral myocarditis: From molecular mechanisms to therapeutic prospects.

Myocarditis is characterized as local or diffuse inflammatory lesions in the myocardium, primarily caused by viruses and other infections. It is a common cause of sudden cardiac death and dilated cardiomyopathy. In recent years, the global prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the widespread vaccination have coincided with a notable increase in the number of reported cases of myocarditis. In light of the potential threat that myocarditis poses to global public health, numerous studies have sought to elucidate the pathogenesis of this condition. However, despite these efforts, effective treatment strategies remain elusive. To collate the current research advances in myocarditis, and thereby provide possible directions for further research, this review summarizes the mechanisms involved in viral invasion of the organism and primarily focuses on how viruses trigger excessive inflammatory responses and in result in different types of cell death. Furthermore, this article outlines existing therapeutic approaches and potential therapeutic targets for the acute phase of myocarditis. In particular, immunomodulatory treatments are emphasized and suggested as the most extensively studied and clinically promising therapeutic options.

LIM domain only 7: a novel driver of immune evasion through regulatory T cell differentiation and chemotaxis in pancreatic ductal adenocarcinoma.

With advancements in genomics and immunology, immunotherapy has emerged as a revolutionary strategy for tumor treatment. However, pancreatic ductal adenocarcinoma (PDAC), an immunologically "cold" tumor, exhibits limited responsiveness to immunotherapy. This study aimed to address the urgent need to uncover PDAC's immune microenvironment heterogeneity and identify the molecular mechanisms driving immune evasion. Using single-cell RNA sequencing datasets and spatial proteomics, we discovered LIM domain only 7 (LMO7) in PDAC cells as a previously unrecognized driver of immune evasion through Treg cell enrichment. LMO7 was positively correlated with infiltrating regulatory T cells (Tregs) and dysfunctional CD8+ T cells. A series of in vitro and in vivo experiments demonstrated LMO7's significant role in promoting Treg cell differentiation and chemotaxis while inhibiting CD8+ T cells and natural killer cell cytotoxicity. Mechanistically, LMO7, through its LIM domain, directly bound and promoted the ubiquitination and degradation of Foxp1. Foxp1 negatively regulated transforming growth factor-beta (TGF-ß) and C-C motif chemokine ligand 5 (CCL5) expression by binding to sites 2 and I/III, respectively. Elevated TGF-ß and CCL5 levels contribute to Treg cell enrichment, inducing immune evasion in PDAC. Combined treatment with TGF-ß/CCL5 antibodies, along with LMO7 inhibition, effectively reversed immune evasion in PDAC, activated the immune response, and prolonged mouse survival. Therefore, this study identified LMO7 as a novel facilitator in driving immune evasion by promoting Treg cell enrichment and inhibiting cytotoxic effector functions. Targeting the LMO7-Foxp1-TGF-ß/CCL5 axis holds promise as a therapeutic strategy for PDAC. Graphical abstract revealing LMO7 as a novel facilitator in driving immune evasion by promoting Tregs differentiation and chemotaxis, inducing CD8+ T/natural killer cells inhibition.

Facet-dependent diversity of Pt-O coordination for Pt 1 /CeO 2 catalysts achieved by oriented atomic deposition.

The surface chemistry of CeO2 is dictated by the well-defined facets, which exert great influence on the supported metal species and the catalytic performance. Here we report Pt1/CeO2 catalysts exhibiting specific structures of Pt-O coordination on different facets by using adequate preparation methods. The simple impregnation method results in Pt-O3 coordination on the predominantly exposed {111} facets, while the photo-deposition method achieves oriented atomic deposition for Pt-O4 coordination into the "nano-pocket" structure of {100} facets at the top. Compared to the impregnated Pt1/CeO2 catalyst showing normal redox properties and low-temperature activity for CO oxidation, the photo-deposited Pt1/CeO2 exhibits uncustomary strong metal-support interaction and extraordinary high-temperature stability. The preparation methods dictate the facet-dependent diversity of Pt-O coordination, resulting in the further activity-selectivity trade-off. By applying specific preparation routes, our work provides an example of disentangling the effects of support facets and coordination environments for nano-catalysts.

Impaired sensitivity to thyroid hormone correlates to all-cause mortality in euthyroid individuals with chronic kidney disease.

BACKGROUND: This study aimed to investigate the association between central sensitivity to thyroid hormones and all-cause mortality in euthyroid patients with chronic kidney disease (CKD). METHODS: ​Data on thyroid function indicators and all-cause mortality for CKD patients were extracted from the NHANES database (2007-2012). Central sensitivities to thyroid hormones were mainly evaluated by Thyroid Feedback Quantile-based Index (TFQI). The Kaplan-Meier method, Cox proportional hazards regression model and subgroup analysis were performed to explore the potential associations between thyroid hormone sensitivity and all-cause mortality. RESULTS: A total of 1303 euthyroid CKD patients were enrolled in this study. After a median follow-up of 115 months, 503 participants died. The Kaplan-Meier analysis demonstrated significant variations in survival rates among different levels of TFQI (P = 0.0015). Cox regression analysis showed that increased levels of TFQI were independent risk factors for all-cause mortality after adjusting for multiple confounding factors (HR = 1.40, 95% CI 1.10-1.79, P = 0.007). Subgroup analysis did not reveal any significant variation in the association between TFQI and all-cause mortality between the subgroups assessed (P for interaction > 0.05). CONCLUSION: Our study suggests that impaired thyroid hormone sensitivity might be linked to increased mortality in euthyroid CKD patients. Further research is needed to confirm and explore this association.

Research trends in the relationship between vitamin D and type 2 diabetes mellitus: a 20-year bibliometric and visualization analysis.

Introduction: Vitamin D has a significant correlation with type 2 diabetes. Insufficient levels of vitamin D can cause insulin resistance, which impairs the ability of cells to respond to insulin and worsens the progression of diseases. Furthermore, vitamin D has the potential to enhance the release of insulin, enhance the regulation of blood sugar levels, and reduce the glycemic index. Research has indicated that insufficient levels of vitamin D may elevate the likelihood of experiencing complications related to type 2 diabetes, including cardiovascular disease and neuropathy. This study employed bibliometric analysis to investigate recent advancements in research about the relationship between vitamin D and type 2 diabetes. Methods: We searched for articles on the topic of vitamin D and type 2 diabetes published between January 1, 2004, and December 31, 2023. The search was performed on February 20, 2024, using the Web of Science Core Collection (WoSCC). Utilizing VOSviewer and CiteSpace, we conducted bibliometric analysis and visualization. Results: A comprehensive study was conducted on a total of 1362 papers pertaining to the relationship between vitamin D and type 2 diabetes. The United States had the biggest number of publications and the highest effect among these articles. Within the top 10 most published journals, the journal "DIABETES CARE" has the highest H-index, indicating its significant influence in this field of study. Currently, there is an extensive body of research on the supplementation of vitamin D for the improvement of type 2 diabetes and prevention of complications in type 2 diabetes, as well as its related mechanisms. Research related to bone turnover and peripheral neuropathy represents a promising area for future studies. Conclusion: Overall, bibliometrics may assist researchers in comprehending the trajectory, significant themes, and scholarly influence of the field concerning vitamin D and type 2 diabetes. This, in turn, offers substantial backing for future studies that delve further into the subject matter.

Class II ferroptosis inducers are a novel therapeutic approach for t(4;14)-positive multiple myeloma.

ABSTRACT: Multiple myeloma (MM) is a clonal plasma cell malignancy that is characterized by genetic heterogeneity. The cytogenetic abnormality t(4;14) strongly predicts poor outcome in patients with MM, even in the era of novel drugs. Ferroptosis is a new approach to antitumor therapy, but the relationship between ferroptosis and MM cytogenetic abnormalities remains largely unclear. In this study, we show that t(4;14)-positive but not t(4;14)-negative MM cells are susceptible to class II ferroptosis inducers (FINs) in a preclinical setting, which is dependent on the significant upregulation of the MM SET domain-containing protein (MMSET). Mechanistically, MMSET upregulates acyl-coenzyme A synthetase long-chain family member 4 transcription by binding to its promoter region, leading to increased polyunsaturated fatty acid (PUFA) levels and enhanced sensitivity of t(4;14)-positive MM cells to ferroptosis. Supplementation with PUFAs efficiently restores the susceptibility of t(4;14)-negative MM cells to ferroptosis. In addition, combining class II FIN treatment with bortezomib in t(4;14)-positive MM cells attenuates cellular glutathione and induces both apoptosis and ferroptosis levels by inhibiting the increase in solute carrier family 7 member 11, demonstrating synergistic antitumor activity in vitro and in a xenograft model. Taken together, our findings suggest that targeting ferroptosis with class II FINs is a novel and promising therapeutic approach to improve the outcome of t(4;14)-positive patients with MM.