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1.
Angew Chem Int Ed Engl ; : e202412401, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39243107

RESUMEN

All-solid-state potassium metal batteries have caught increasing interest owing to their abundance, cost-effectiveness, and high energy/power density. However, their development is generally constrained by the lack of suitable solid-state electrolytes. Herein, we report a new complex KCB9H10·2C3H4N2, synthesized by grinding and heating the mixture of potassium decahydrido-monocarba-closo-decaborate (KCB9H10) and imidazole (C3H4N2) under mild conditions, to achieve the K-ion superionic solid-state electrolyte. The crystal structure was revealed as an orthorhombic lattice with the space group of Pna21 by FOX software. The diffusion properties for K+ in the crystal structure were calculated using the climbing image nudged elastic band (CI-NEB) method. KCB9H10·2C3H4N2 exhibited a high ionic conductivity of 1.3 × 10-4 S cm-1 at 30 °C, four orders of magnitude higher than that of KCB9H10. This ionic conductivity is also the highest value of hydridoborate-based K+ conductors reported. Moreover, KCB9H10·2C3H4N2 demonstrated a K+ transference number of 0.96, an electrochemical stability window of 1.2 to 3.2 V vs. K/K+, and good stability against the K metal coated by a layer of potassium imidazolate (KIm). These great performances make KCB9H10·2C3H4N2 a promising K-ion solid-state electrolyte.

2.
Curr Opin Ophthalmol ; 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39259650

RESUMEN

PURPOSE OF REVIEW: Patient privacy protection is a critical focus in medical practice. Advances over the past decade in big data have led to the digitization of medical records, making medical data increasingly accessible through frequent data sharing and online communication. Periocular features, iris, and fundus images all contain biometric characteristics of patients, making privacy protection in ophthalmology particularly important. Consequently, privacy-preserving technologies have emerged, and are reviewed in this study. RECENT FINDINGS: Recent findings indicate that general medical privacy-preserving technologies, such as federated learning and blockchain, have been gradually applied in ophthalmology. However, the exploration of privacy protection techniques of specific ophthalmic examinations, like digital mask, is still limited. Moreover, we have observed advancements in addressing ophthalmic ethical issues related to privacy protection in the era of big data, such as algorithm fairness and explainability. SUMMARY: Future privacy protection for ophthalmic patients still faces challenges and requires improved strategies. Progress in privacy protection technology for ophthalmology will continue to promote a better healthcare environment and patient experience, as well as more effective data sharing and scientific research.

3.
Health Aff (Millwood) ; 43(9): 1296-1305, 2024 09.
Artículo en Inglés | MEDLINE | ID: mdl-39226503

RESUMEN

Dual-eligible beneficiaries have insurance through two distinct and uncoordinated programs: Medicaid, which pays for long-term care; and Medicare, which pays for medical care, including hospital stays. Concern that this system leads to poor quality and inefficient care, particularly for dual-eligible nursing home residents, has led policy makers to test managed care plans that provide incentives for coordinating care across Medicare and Medicaid. We examined enrollment in three such plans among dual-eligible beneficiaries receiving long-term nursing home care. Two of those plans, Medicare-Medicaid plans and Fully Integrated Dual Eligible Special Needs Plans, are integrated care plans that establish a global budget including Medicare and Medicaid spending. The third, Institutional Special Needs Plans, puts insurers and nursing homes at risk for Medicare spending but not Medicaid spending. Among dual-eligible nursing home residents, enrollment in these plans increased from 6.5 percent of residents per month in 2013 to 16.9 percent in 2020. Enrollment varied across counties but did not vary appreciably with respect to nursing home characteristics, including the share of residents with Medicaid. As policy makers pursue strategies to coordinate medical and long-term care for dual-eligible beneficiaries, it remains critical to evaluate how these plans influence the care of dual-eligible nursing home residents.


Asunto(s)
Determinación de la Elegibilidad , Programas Controlados de Atención en Salud , Medicaid , Medicare , Casas de Salud , Estados Unidos , Humanos , Medicare/economía , Anciano , Femenino , Masculino , Anciano de 80 o más Años , Cuidados a Largo Plazo/economía , Gastos en Salud/estadística & datos numéricos
4.
Ann Surg ; 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39291384

RESUMEN

OBJECTIVE: To determine the proportion and characteristics of injured rural residents treated at urban trauma centers (TCs), urban non-trauma centers (NTCs), rural TCs, and rural NTCs. SUMMARY BACKGROUND DATA: Timely treatment at a designated trauma center improves outcomes for patients with serious injuries, but rural residents have limited access to designated trauma centers. Rural non-trauma centers may constitute an underrecognized source of trauma care. METHODS: We used the National Emergency Department Sample to conduct a retrospective, pooled cross-sectional study of ED visits among rural residents with injury severity score (ISS) ≥ 9 (indicating at least moderate injury). Hospitals were designated as a trauma (TC) or non-trauma center (NTC) and as rural or urban. We compared management, disposition, and outcomes among hospital types. RESULTS: Of 748,587 injured rural residents from 2016-2020, 384,113 (51.3%) were treated in rural NTCs, 232,845 (31.1%) in urban TCs, 116,493 (15.6%) in urban NTCs, and 15,137 (2.0%) in rural TCs. Injuries treated at rural NTCs were moderate in severity (ISS 9-15) in 76.6% of visits, severe (ISS 16-25) in 15.7%, and very severe (ISS > 25) in 1.1%. Urban TCs saw the highest proportion of very severe injuries (17.3%). Rural NTCs managed 77.5% of visits definitively, discharging 72.8%. They transferred 21.9% of patients. Length of stay was longest and hospital charges highest for patients treated in urban TCs, which also performed the most procedures. Rural NTCs had the shortest length of stay and lowest mean charges. CONCLUSIONS: Rural non-trauma centers provided initial care for more than half of injured rural residents, including 2 in 5 of those with the most severe injuries, and managed more than 3 in 4 definitively. These hospitals may be an under-recognized component of the US trauma system.

5.
Transl Pediatr ; 13(7): 1201-1209, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39144427

RESUMEN

Background: Sialyllacto-N-tetraose b (LSTb) is a component of human milk oligosaccharides. Due to its low concentration, the impact of LSTb on neurodevelopment remains largely unexplored. It is worth studying whether LSTb should be added to infant formula to simulate breast milk. This study aimed to investigate the effect of LSTb on the development of motor neurons of the central nervous system using a transgenic zebrafish model. Methods: Transgenic (Tg) zebrafish line (Hb9:GFP) was incubated with LSTb, and the axonal growth of caudal primary (CaP) neurons was assessed. Locomotor behavior was evaluated, and RNA sequencing (RNA-seq) was performed to identify the differentially expressed genes (DEGs). The expression of Slit2 and Slit3, genes involved in axon guidance, was further analyzed through real-time polymerase chain reaction (real-time PCR) and whole-mount in situ hybridization. Results: There was a significant increase in the number and length of CaP axon branches, suggesting that LSTb promotes CaP development. Behavioral analysis revealed enhanced locomotor activity in LSTb-treated larvae, indicating improved motor function. RNA-seq analysis identified 5,847 DEGs related to central nervous system neuron differentiation, including Slit2 and Slit3, which are known to contribute to axon guidance. In situ hybridization confirmed increased Slit2 expression in the central nervous system of LSTb-treated larvae. Conclusions: LSTb significantly influences motor neuron development, potentially through the upregulation of Slit2 and Slit3. This research provides valuable insights into the role of LSTb in neurodevelopment.

6.
Health Aff Sch ; 2(6): qxae056, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38915810

RESUMEN

Safety-net hospitals have recently become targets of acquisition by health systems with the stated purpose of improving their financial solvency and preserving access to safety-net services. Whether acquisition achieves these goals is unknown. In this descriptive case series, we sought to determine the factors that contribute to safety-net hospital acquisition, and identify whether safety-net services are preserved after acquisition. We examined 22 acquisitions of safety-net hospitals from 2016 to 2021 and described characteristics of the acquired safety-net hospitals, their acquiring systems, and the operational fate of acquired hospitals. Relative to other hospitals in the same Hospital Referral Region in the year prior to acquisition, acquired safety-net hospitals tended to be smaller and have lower occupancy rates. Acquiring systems were geographically concentrated, with only 6 of 20 systems operating in more than 1 state. Safety-net hospitals frequently offered typical safety-net services prior to acquisition. However, after acquisition, 2 of the 22 acquired safety-net hospitals lost safety-net services, 3 hospitals ceased inpatient services, and 1 hospital closed entirely. These findings suggest that acquisition of safety-net hospitals may be associated with trade-offs related to the provision of safety-net services for the communities that stand to benefit from them most.

7.
J Hazard Mater ; 474: 134803, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-38850931

RESUMEN

The release of sludge-derived heavy metals (HMs) to soil and their subsequent migration into groundwater poses a significant challenge for safe and low-carbon sludge land application. This study developed a predictive framework to simulate 60-year sludge land application, evaluating the risk of HMs pollution in the soil-groundwater environment and assessing the influence of soil and water properties. HYDRUS-2D simulations revealed that highly mobile Cu, Ni, and Zn penetrated a 10 m soil layer over a 60-year period, contributing to groundwater pollution. In contrast, Cr was easily sequestered within the topsoil layer after 5-years continuous operation. The non-equilibrium parameter α could serve as an indicator for assessing their potential risk. Furthermore, the limited soil adsorption sites for Pb (f = 0.02772) led to short-term (1-year) groundwater pollution at a 0.5 m-depth. Bayesian Networks model outcomes indicated that humic-like organics crucially influenced HMs transformation, enhancing the desorption of Cd, Cu, Ni, Pb, and Zn, while inhibiting the desorption for Cr. Additionally, electrical conductivity promoted the release of most HMs, in contrast to the Mn mineralogy in soil. This study bridges the gap between the macro-level HMs migration trends and the micro-level adsorption-desorption characteristics, providing guidance for the safe land application of sewage sludge. ENVIRONMENTAL IMPLICATION: This study introduces a framework integrating HYDRUS-2D simulations with Bayesian Networks to assess the risks of groundwater pollution by heavy metals (HMs) over a 60-year sludge application. Sludge-derived Cu, Ni, and Zn are found to penetrate soil up to 10 m and exceed safety limits, with the non-equilibrium parameter α serving as an indicator for pollution risk. The importance of nutrients from sludge-amended soil for the transformation of HMs in the subsurface environment highlights the need for enhanced sludge management, specifically through more detailed regulation of nutrient composition. These findings contribute to developing precise strategies for the long-term sludge land application.

8.
Mucosal Immunol ; 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38866206

RESUMEN

Corneal wound healing in diabetic patients is usually delayed and accompanied by excessive inflammation. However, the underlying cellular and molecular mechanisms remain poorly understood. Here, we found that somatostatin (SST), an immunosuppressive peptide produced by corneal nerve fibers, was significantly reduced in streptozotocin-induced diabetic mice. In addition, we discovered that topical administration of exogenous SST significantly improved re-epithelialization and nerve regeneration following diabetic corneal epithelial abrasion. Further analysis showed that topical SST significantly reduced the expression of injury inflammation-related genes, inhibited neutrophil infiltration, and shifted macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 in diabetic corneas' healing. Moreover, the application of L-817,818, an agonist of the SST receptor type 5 subtype, significantly reduced the inflammatory response following epithelial injury and markedly improved the process of re-epithelialization and nerve regeneration in mice. Taken together, these data suggest that activation of the SST-SST receptor type 5 pathway significantly ameliorates diabetes-induced abnormalities in corneal wound repair in mice. Targeting this pathway may provide a novel strategy to restore impaired corneal wound closure and nerve regeneration in diabetic patients.

9.
Small ; : e2401439, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38845528

RESUMEN

Solid-state sodium metal batteries have been extensively investigated because of their potential to improve safety, cost-effectiveness, and energy density. The development of such batteries urgently required a solid-state electrolyte with fast Na-ion conduction and favorable interfacial compatibility. Herein, the progress on developing the NaB3H8 solid-state electrolytes is reported, which show a liquid-like ionic conductivity of 0.05 S cm-1 at 56 °C with an activation energy of 0.35 eV after an order-disorder phase transformation, matching or surpassing the best single-anion hydridoborate conductors investigated up to now. The steady polarization voltage and significantly decreased resistance are achieved in the symmetric Na/NaB3H8/Na cell, indicating the great electrochemical stability and favorable interfacial contact with the Na metal of NaB3H8. Furthermore, a Na/NaB3H8/TiS2 battery, the first high-rate (up to 1 C) solid-state sodium metal battery using the single-anion hydridoborate electrolyte, is demonstrated, which exhibits superior rate capability (168.2 mAh g-1 at 0.1 C and 141.2 mAh g-1 at 1 C) and long-term cycling stability (70.9% capacity retention at 1 C after 300 cycles) at 30 °C. This work may present a new possibility to solve the interfacial limitations and find a new group of solid-state electrolytes for high-performance sodium metal batteries.

10.
Nutr Hosp ; 41(3): 657-665, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38666335

RESUMEN

Introduction: Background and aims: although sarcopenia is associated with several types of cancer, there is limited research regarding its effect on breast cancer. We aimed to explore the causality between sarcopenia-related traits and the incidence and prognosis of breast cancer. Methods: two-sample bidirectional and multivariate Mendelian randomization (MR) analyses were utilized in this study. Genome-wide association studies were used to genetically identify sarcopenia-related traits, such as appendicular lean mass, grip strength of both hands, and walking pace. Data on the incidence and prognosis of breast cancer were collected from two extensive cohort studies. Multivariate MR analysis was used to adjust for body mass index, waist circumference, and whole-body fat mass. The primary method used for analysis was inverse-variance weighted analysis. Results: a significant association was found between appendicular lean mass and ER- breast cancer (OR = 0.873, 95 % CI: 0.817-0.933, p = 6.570 × 10-5). Increased grip strength of the left hand was associated with a reduced risk of ER- breast cancer (OR = 0.744, 95 % CI: 0.579-0.958, p = 0.022). Stronger grip strength of the right hand was associated with prolonged survival time of ER+ breast cancer patients (OR = 0.463, 95 % CI: 0.242-0.882, p = 0.019). In the multivariable MR analysis, appendicular lean mass, grip strength of both hands, and walking pace were still genetically associated with the development of total breast cancer and ER-/+ breast cancer. Conclusions: several sarcopenia-related traits were genetically associated with the occurrence and prognosis of breast cancer. It is crucial for elderly women to increase their strength and muscle mass to help prevent breast cancer.


Introducción: Antecedentes y objetivos: aunque la sarcopenia se asocia a múltiples tipos de cáncer, los estudios sobre sus efectos sobre el cáncer de mama son limitados. Nuestro objetivo es explorar la relación causal entre las características relacionadas con la sarcopenia y la incidencia y el pronóstico del cáncer de mama. Método: este estudio utilizó un análisis de aleatorización mendeliana (MR) bidireccional y multivariable de doble muestra. Los estudios de asociación genómica completa se utilizan para identificar genéticamente características relacionadas con la sarcopenia, como la masa magra apendicular, la fuerza de agarre de las manos y la velocidad al caminar. Los datos de incidencia y pronóstico del cáncer de mama provienen de dos amplios estudios de cohortes. El análisis de MR multivariable se utilizó para ajustar el índice de masa corporal, la circunferencia de la cintura y la masa grasa corporal total. El principal método de análisis fue el análisis ponderado por ANOVA inverso. Resultados: la masa magra apendicular se asoció significativamente al cáncer de mama ER- (OR = 0,873, IC 95 %: 0,817-0,933, p = 6,570 × 10-5), el aumento de la fuerza de agarre del lado izquierdo se asoció a una disminución del riesgo de cáncer de mama ER- (OR = 0,744, IC 95 %: 0,579-0,958, p = 0,022) y el aumento de la fuerza de agarre del lado derecho se asoció a una mayor supervivencia de los pacientes con cáncer de mama ER+ (OR = 0,463, IC 95 %: 0,24-0,882, P = 0,019). En el análisis MR multivariable, la masa magra apendicular, la fuerza de agarre de ambas manos y la velocidad al caminar mantuvieron su asociación genética con la aparición del cáncer de mama total y del cáncer de mama ER-/+. Conclusión: varios rasgos relacionados con la sarcopenia tienen correlación genética con la aparición y el pronóstico del cáncer. Mejorar la fuerza y la masa muscular de las mujeres mayores es fundamental para ayudar a prevenir el cáncer de mama.


Asunto(s)
Neoplasias de la Mama , Fuerza de la Mano , Análisis de la Aleatorización Mendeliana , Sarcopenia , Humanos , Neoplasias de la Mama/genética , Sarcopenia/genética , Sarcopenia/epidemiología , Femenino , Pronóstico , Persona de Mediana Edad , Estudio de Asociación del Genoma Completo , Anciano , Estudios de Cohortes , Incidencia
11.
Bioresour Technol ; 400: 130678, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38588784

RESUMEN

Proteins and carbohydrates are important organics in waste activated sludge, and greatly affect methane production and microbial community composition in anaerobic digestion systems. Here, a series of co-substrates with different molecular weight were applied to investigate the interactions between microbial dynamics and the molecular weight of co-substrates. Biochemical methane production assays conducted in batch co-digesters showed that feeding high molecular weight protein and carbohydrate substrates resulted in higher methane yield and production rates. Moreover, high-molecular weight co-substrates increased the microbial diversity, enriched specific microbes including Longilinea, Anaerolineaceae, Syner-01, Methanothrix, promoted acidogenic and acetoclastic methanogenic pathways. Low-molecular weight co-substrates favored the growth of JGI-0000079-D21, Armatimonadota, Methanosarcina, Methanolinea, and improved hydrogenotrophic methanogenic pathway. Besides, Methanoregulaceae and Methanolinea were indicators of methane yield. This study firstly revealed the complex interactions between co-substrate molecular weight and microbial communities, and demonstrated the feasibility of adjusting co-substrate molecular weight to improve methane production process.


Asunto(s)
Metano , Peso Molecular , Aguas del Alcantarillado , Metano/metabolismo , Aguas del Alcantarillado/microbiología , Anaerobiosis , Redes y Vías Metabólicas , Reactores Biológicos , Bacterias/metabolismo
12.
Mucosal Immunol ; 17(2): 211-225, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38331094

RESUMEN

Allergic conjunctivitis (AC), an allergen-induced ocular inflammatory disease, primarily involves mast cells (MCs) and eosinophils. The role of neuroimmune mechanisms in AC, however, remains to be elucidated. We investigated the effects of transient receptor potential vanilloid 1 (TRPV1)-positive sensory nerve ablation (using resiniferatoxin) and TRPV1 blockade (using Acetamide, N-[4-[[6-[4-(trifluoromethyl)phenyl]-4-pyrimidinyl]oxy]-2-benzothiazolyl] (AMG-517)) on ovalbumin-induced conjunctival allergic inflammation in mice. The results showed an exacerbation of allergic inflammation as evidenced by increased inflammatory gene expression, MC degranulation, tumor necrosis factor-α production by MCs, eosinophil infiltration and activation, and C-C motif chemokine 11 (CCL11) (eotaxin-1) expression in fibroblasts. Subsequent findings demonstrated that TRPV1+ sensory nerves secrete somatostatin (SST), which binds to SST receptor 5 (SSTR5) on MCs and conjunctival fibroblasts. SST effectively inhibited tumor necrosis factor-α production in MCs and CCL11 expression in fibroblasts, thereby reducing eosinophil infiltration and alleviating AC symptoms, including eyelid swelling, lacrimation, conjunctival chemosis, and redness. These findings suggest that targeting TRPV1+ sensory nerve-mediated SST-SSTR5 signaling could be a promising therapeutic strategy for AC, offering insights into neuroimmune mechanisms and potential targeted treatments.


Asunto(s)
Antineoplásicos , Conjuntivitis Alérgica , Ratones , Animales , Factor de Necrosis Tumoral alfa/metabolismo , Conjuntiva/metabolismo , Conjuntiva/patología , Eosinófilos , Antineoplásicos/efectos adversos , Inflamación/metabolismo , Canales Catiónicos TRPV/genética , Canales Catiónicos TRPV/metabolismo
13.
ACS Appl Mater Interfaces ; 16(8): 10070-10077, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38380614

RESUMEN

All-solid-state potassium metal batteries have been considered promising candidates for large-scale energy storage because of abundance and wide availability of K resources, elimination of flammable liquid organic electrolytes, and incorporation of high-capacity K metal anode. However, unideal K-ion conductivities of most reported K-ion solid electrolytes have restricted the development of these batteries. Herein, a novel K2B10H10·CO(NH2)2 complex is reported, forming by incorporating urea into K2B10H10, to achieve an enhanced K-ion conductivity. The crystal structure of K2B10H10·CO(NH2)2 was determined as a monoclinic lattice with the space group of C2/c (No. 15). K2B10H10·CO(NH2)2 delivers an ionic conductivity of 2.7 × 10-8 S cm-1 at 25 °C, and reaching 1.3 × 10-4 S cm-1 at 80 °C, which is about 4 orders of magnitude higher than that of K2B10H10. One possible reason is the anion expansion in size due to the presence of dihydrogen bonds in K2B10H10·CO(NH2)2, resulting in an increase in the K-H bond distance and the electrostatic potential, thereby enhancing the mobility of K+. The K-ion conductivity is also higher than those of most hydridoborate-based K-ion conductors reported. Besides, K2B10H10·CO(NH2)2 reveals a wide electrochemical stability window and remarkable interface compatibility with K metal electrodes, suggesting a promising electrolyte for all-solid-state K metal batteries.

14.
Angew Chem Int Ed Engl ; 63(17): e202401480, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38351436

RESUMEN

All-solid-state sodium metal batteries are promising for large-scale energy storage applications owing to their intrinsic safety and cost-effectiveness. However, they generally suffer from sodium dendrite growth or rapid capacity fading, especially at high rates, mainly due to poor wettability, sluggish ionic transport, or low interfacial stability of the solid electrolytes. Herein, we report a novel composite, NaB3H8 ⋅ xNH3@NaB3H8 (x<1), as a new class of solid electrolyte for high-rate batteries. NaB3H8 ⋅ xNH3@NaB3H8 is obtained from the sticky NaB3H8 ⋅ NH3 after removal of NH3 partially at room temperature. It delivers an ionic conductivity of 0.84 mS cm-1 at 25 °C and reaches 20.64 mS cm-1 at 45 °C after an order-disorder phase transformation. It also reveals a good capability of dendrite suppression and remarkable stability against sodium metal. These performances enable the all-solid-state Na//TiS2 battery with a high capacity of 232.4 mAh g-1 (97.2 % of theoretical capacity) and long-term cycling stability at 1 C. Notably, this battery shows superior long-life cycling stability even at 5 and 10 C, which has been rarely reported in all-solid-state sodium metal batteries. This work opens a new group of solid electrolytes, contributing to fast-charging or high-power-density sodium metal batteries.

15.
PLoS One ; 19(1): e0298247, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38295085

RESUMEN

[This corrects the article DOI: 10.1371/journal.pone.0295565.].

16.
Heliyon ; 10(1): e23589, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38187270

RESUMEN

Inflammatory macrophages within the synovium play a pivotal role in the progression of arthritis inflammation. Effective drug therapy targeting inflammatory macrophages has long been a goal for clinicians and researchers. The standard approach for treating osteoarthritis (OA) involves systemic treatment and local injection. However, the high incidence of side effects associated with long-term drug administration increases the risk of complications in patients. Additionally, the rapid clearance of the joint cavity poses a biological barrier to the therapeutic effect. NADPH oxidase 4 (NOX4) is an enzyme protein regulating the cellular redox state by generating reactive oxygen species (ROS) within the cell. In this study, we designed and fabricated a hydrogel microsphere consisting of methyl methacrylate (MMA) and polyvinyl acetate (PVA) as the outer layer structure. We then loaded GLX351322 (GLX), a novel selective NOX4 inhibitor, into hydrogel microspheres through self-assembly with the compound polyethylene glycol ketone mercaptan (mPEG-TK) containing a disulfide bond, forming nanoparticles (mPEG-TK-GLX), thus creating a two-layer drug-loaded microspheres capsule with ROS-responsive and slow-releasing capabilities. Our results demonstrate that mPEG-TK-GLX@PVA-MMA effectively suppressed TBHP-induced inflammation, ROS production, and ferroptosis, indicating a promising curative strategy for OA and other inflammatory diseases in the future.

17.
Cell Commun Signal ; 22(1): 81, 2024 01 30.
Artículo en Inglés | MEDLINE | ID: mdl-38291404

RESUMEN

BACKGROUND: Previous research has revealed that the 18 glycoside hydrolase gene family (GH18) member Chitinase 3-like 1 (Chi3l1) can regulate osteoclast differentiation and bone resorption. However, its downstream receptors and molecular mechanisms during osteoclastogenesis have yet to be elucidated. METHODS: Initially, we conducted a comprehensive investigation to evaluate the effects of recombinant Chi3l1 protein or Chi3l1 siRNA on osteoclast differentiation and the RANKL-induced MAPK/AKT signaling pathways. Moreover, we used immunofluorescence and immunoprecipitation assays to identify IL13Rα2 as the downstream receptor of Chi3l1. Subsequently, we investigated the impact of IL13Rα2 recombinant protein or IL13Rα2-siRNA on osteoclast differentiation and the associated signaling pathways. Finally, we performed in vivo experiments to examine the effect of recombinant IL13Rα2 protein in an LPS-induced mouse model of cranial osteolysis. RESULTS: Our findings highlight that the administration of recombinant Chi3l1 protein increased the formation of osteoclasts and bolstered the expression of several osteoclast-specific genes (TRAP, NFATC1, CTR, CTSK, V-ATPase d2, and Dc-STAMP). Additionally, Chi3l1 significantly promoted the RANKL-induced MAPK (ERK/P38/JNK) and AKT pathway activation, whereas Chi3l1 silencing inhibited this process. Next, using immunofluorescence and co-immunoprecipitation assays, we identified IL13Rα2 as the binding partner of Chi3l1 during osteoclastogenesis. IL13Rα2 recombinant protein or IL13Rα2-siRNA also inhibited osteoclast differentiation, and IL13Rα2-siRNA attenuated the RANKL-induced activation of the MAPK (ERK/P38/JNK) and AKT pathways, similar to the effects observed upon silencing of Chi3l1. Moreover, the promoting effect of recombinant Chi3l1 protein on osteoclastogenesis and the activation of the MAPK and AKT pathways was reversed by IL13Rα2 siRNA. Finally, recombinant LI13Rα2 protein significantly attenuated the LPS-induced cranial osteolysis and the number of osteoclasts in vivo. CONCLUSIONS: Our findings suggested that IL13Rα2 served as a crucial receptor for Chi3l1, enhancing RANKL-induced MAPK and AKT activation to promote osteoclast differentiation. These findings provide valuable insights into the molecular mechanisms of Chi3l1 in osteoclastogenesis, with potential therapeutic implications for osteoclast-related diseases. Video Abstract.


Asunto(s)
Resorción Ósea , Subunidad alfa2 del Receptor de Interleucina-13 , Osteólisis , Animales , Ratones , Resorción Ósea/tratamiento farmacológico , Diferenciación Celular , Proteína 1 Similar a Quitinasa-3/metabolismo , Subunidad alfa2 del Receptor de Interleucina-13/metabolismo , Subunidad alfa2 del Receptor de Interleucina-13/uso terapéutico , Lipopolisacáridos/farmacología , Factores de Transcripción NFATC/metabolismo , Osteoclastos , Osteólisis/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ligando RANK/metabolismo , Proteínas Recombinantes/farmacología , ARN Interferente Pequeño/metabolismo
18.
J Hazard Mater ; 466: 133552, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38246061

RESUMEN

Increasing occurrence of heavy metals (HMs) in sewage sludge threatens its widespread land utilization in China due to its potential impact on nutrient cycling in soil, requiring a better understanding of HM-induced impacts on nitrification. Herein, lab-scale experiments were conducted over 185-day, evaluating the effect of sludge-derived chromium (Cr3+), nickel (Ni2+), and lead (Pb2+) on soil nitrification at different concentrations. Quantitative polymerase chain reaction and linear regression results revealed an inhibitory sequence of gene abundance by HMs' labile fraction: ammonia-oxidizing bacteria (AOB)-ammonia monooxygenase (amoA)> nitrite oxidoreductase subunit alpha (nxrA)> nitrite oxidoreductase subunit beta (nxrB). The toxicity of HMs' incremental labile fraction decreased in the order of Ni2+>Cr3+>Pb2+, with respective threshold values of 5.01, 24.03 and 38.42 mg·kg-1. Furthermore, extending incubation time reduced HMs inhibition on ammonia oxidation, mainly related to their fraction bound to carbonate minerals. Random Forest analysis, variation partitioning analysis, and Mantel test indicated that soil physicochemical properties primarily affected nitrification genes, especially in the test of Cr3+ on AOB-amoA, nxrA, nxrB, Ni2+ for complete ammonia-oxidizing bacteria-amoA, and Pb2+ for nxrA and nxrB. These findings underline the importance of labile HMs fractions and soil physicochemical properties to nitrification, guiding the establishment of HM control standards for sludge utilization.


Asunto(s)
Bacterias , Metales Pesados , Bacterias/metabolismo , Archaea/metabolismo , Nitrificación , Suelo/química , Aguas del Alcantarillado/química , Cromo/toxicidad , Cromo/metabolismo , Níquel , Plomo/metabolismo , Nitritos/metabolismo , Amoníaco/metabolismo , Oxidación-Reducción , Oxidorreductasas/metabolismo , Metales Pesados/toxicidad , Metales Pesados/metabolismo , Microbiología del Suelo
19.
Environ Toxicol ; 39(3): 1811-1821, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38073300

RESUMEN

BACKGROUND: Gastric cancer is the most common malignant tumour of the digestive system, yet there is a lack of reported prognostic biomarkers for STAD patients. METHODS: Transcriptomic expression data of STAD from GEO database, single cell sequencing data from OMIX gastric cancer database. Conservative molecular typing of gastric cancer was constructed using non-negative matrix factorization (NMF). The abundance of 28 immune cells in the tumour samples was assessed using ssGSEA. The R package "oncoPredict" was used to predict chemotherapy response. TIDE website for immunotherapy response prediction. Finally, single cell analysis was performed to clarify the specific type annotation of STAD cells and to analysis their spatial expression. RESULTS: Hypoxia-score demonstrated excellent prognostic discrimination in TCGA gastric cancer samples. Among multiple deconvolution-based algorithms for immune infiltration, Hypoxia-score presented a general immunosuppressive efficacy across multiple datasets, as evidenced by a broad negative correlation with immune cell infiltration. By the likelihood that each group may have specific drug sensitivity to multiple chemotherapeutic and targeted agents. Results showed that high-risk scoring patients were more sensitive to Staurosporine, Sabutoclax, and AZD8055, while low-risk patients were more sensitive to Bortezomib, Dactinomycin, Docetaxel, Daporinad, Sepantronium, and bromide. In the immunotherapy cohort, the Hypoxia-score presented the ability to discriminate for immunotherapy efficacy. The distribution of Hypoxia-score in single-cell descending space was calculated using AddModuleScore and was found to be distributed across the various cell types annotated in the single-cell analysis. It is suggested that various cells in the tumour microenvironment are involved in hypoxia gene set processes to varying degrees. CONCLUSION: The Hypoxia-score proves to be a valuable tool for assessing the prognosis of gastric cancer patients and guiding drug treatments, providing significant guidance for clinical diagnosis and treatment in the context of gastric cancer.


Asunto(s)
Adenocarcinoma , Neoplasias Gástricas , Humanos , Pronóstico , Docetaxel , Biomarcadores , Microambiente Tumoral
20.
PLoS One ; 18(12): e0295565, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38079443

RESUMEN

Identification of sugarcane stem nodes is generally dependent on high-performance recognition equipment in sugarcane seed pre-cutting machines and inefficient. Accordingly, this study proposes a novel lightweight architecture for the detection of sugarcane stem nodes based on the YOLOv5 framework, named G-YOLOv5s-SS. Firstly, the study removes the CBS and C3 structures at the end of the backbone network to fully utilize shallow-level feature information. This enhances the detection performance of sugarcane stem nodes. Simultaneously, it eliminates the 32 times down-sampled branches in the neck structure and the 20x20 detection heads at the prediction end, reducing model complexity. Secondly, a Ghost lightweight module is introduced to replace the conventional convolution module in the BottleNeck structure, further reducing the model's complexity. Finally, the study incorporates the SimAM attention mechanism to enhance the extraction of sugarcane stem node features without introducing additional parameters. This improvement aims to enhance recognition accuracy, compensating for any loss in precision due to lightweight modifications. The experimental results showed that the average precision of the improved network for sugarcane stem node identification reached 97.6%, which was 0.6% higher than that of the YOLOv5 baseline network. Meanwhile, a model size of 2.6MB, 1,129,340 parameters, and 7.2G FLOPs, representing respective reductions of 82%, 84%, and 54.4%. Compared with mainstream one-stage target detection algorithms such as YOLOv4-tiny, YOLOv4, YOLOv5n, YOLOv6n, YOLOv6s, YOLOv7-tiny, and YOLOv7, G-YOLOv5s-SS achieved respective average precision improvements of 12.9%, 5.07%, 3.6%, 2.1%, 1.2%, 3%, and 0.4% in sugarcane stem nodes recognition. Meanwhile, the model size was compressed by 88.9%, 98.9%, 33.3%, 72%, 92.9%, 78.8% and 96.3%, respectively. Compared with similar studies, G-YOLOv5s-SS not only enhanced recognition accuracy but also considered model size, demonstrating an overall excellent performance that aligns with the requirements of sugarcane seed pre-cutting machines.


Asunto(s)
Saccharum , Algoritmos , Membrana Eritrocítica , Integración Escolar , Cuello
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