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1.
ACS Appl Mater Interfaces ; 16(28): 36735-36744, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38952105

RESUMEN

The piezoelectric properties of two-dimensional semiconductor nanobubbles present remarkable potential for application in flexible optoelectronic devices, and the piezoelectric field has emerged as an efficacious pathway for both the separation and migration of photogenerated electron-hole pairs, along with inhibition of recombination. However, the comprehension and control of photogenerated carrier dynamics within nanobubbles still remain inadequate. Hence, this study is dedicated to underscore the importance of in situ detection and detailed characterization of photogenerated electron-hole pairs in nanobubbles to enrich understanding and strategic manipulation in two-dimensional semiconductor materials. Utilizing frequency modulation kelvin probe force microscopy (FM-KPFM) and strain gradient distribution techniques, the existence of a piezoelectric field in monolayer WS2 nanobubbles was confirmed. Combining w/o and with illumination FM-KPFM, second-order capacitance gradient technique and in situ nanoscale tip-enhanced photoluminescence characterization techniques, the interrelationships among the piezoelectric effect, interlayer carrier transfer, and the funneling effect for photocarrier dynamics process across various nanobubble sizes were revealed. Notably, for a WS2/graphene bubble height of 15.45 nm, a 0 mV surface potential difference was recorded in the bubble region w/o and with illumination, indicating a mutual offset of piezoelectric effect, interlayer carrier transfer, and the funneling effect. This phenomenon is prevalent in transition metal dichalcogenides materials exhibiting inversion symmetry breaking. The implication of our study is profound for advancing the understanding of the dynamics of photogenerated electron-hole pair in nonuniform strain piezoelectric systems, and offers a reliable framework for the separation and modulation of photogenerated electron-hole pair in flexible optoelectronic devices and photocatalytic applications.

2.
Int J Clin Pharm ; 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38990458

RESUMEN

BACKGROUND: Although amivantamab has shown clinical benefits for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) exon 20 insertions, its cost-effectiveness requires further investigation. AIM: To evaluate the cost-effectiveness of amivantamab plus chemotherapy for the treatment of NSCLC patients with EGFR exon 20 insertions from the United States payer perspective. METHOD: A partitioned survival model was developed based on the data from the PAPILLON trial. Costs were derived from the pricing files of Medicare and Medicaid Services and published literature, and utility values were derived from previous studies. A 3% annual discount rate was applied to both costs and outcomes. The primary outcome was the incremental cost-effectiveness ratio (ICER). One-way sensitivity analysis, probabilistic sensitivity analysis and scenario analysis, were conducted to test the model stability. RESULTS: Amivantamab plus chemotherapy yielded an additional 1.12 quality-adjusted life years (QALYs) while increasing costs by $483,769.50 relative to the chemotherapy regimen, leading to an ICER of $432,401.16/QALY. The combination of amivantamab with chemotherapy was not cost effective at a threshold of $150,000/QALY. In the scenario analysis, the results showed that the ICERs were $263,680.69/QALY and $418,416.35/QALY when different utility values and 10-year time horizons were adopted, respectively. For PSA, the probability that amivantamab plus chemotherapy would be cost-effective was 0% if the willingness-to-pay (WTP) threshold was $150,000/QALY. CONCLUSION: Amivantamab plus chemotherapy is unlikely to be a cost-effective option for NSCLC patients with EGFR exon 20 insertions. Reducing the cost of amivantamab may produce favorable economic outcomes.

3.
World J Gastrointest Surg ; 16(6): 1537-1547, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38983355

RESUMEN

BACKGROUND: The optimal extent of lymphadenectomy in esophageal squamous cell carcinoma (ESCC) patients remained debatable. AIM: To explore the ideal number of cleared lymph nodes in ESCC patients undergoing upfront surgery. METHODS: In this retrospective, propensity score-matched study, we included 1042 ESCC patients who underwent esophagectomy from November 2008 and October 2019. Patients who underwent neoadjuvant therapy were excluded. We collected patients' clinicopathological features and information regarding lymph nodes, including the total number of resected lymph nodes (NRLN), and pathologically diagnosed positive lymph nodes (RPLN). SPSS and R software were used for statistical analysis. RESULTS: Among the included 1042 patients, two cohorts: ≤ 21 (n = 664) and > 21 NRLN (n = 378) were identified. The final prognostic model included four variables: T stage, N, venous thrombus, and the number of removed lymph nodes. Among them, NRLN > 21 was determined as an independent prognosticator after surgery for esophageal cancer (hazards regression = 0.66, 95% confidence interval: 0.50-0.87, P = 0.004). A nomogram was created based on the regression coefficients of the variables in the final model. In the training cohort, the predictive model displayed an uncorrected five-year overall survival C-index of 0.659, with a bootstrap-corrected C-index of 0.654. In the subgroup analysis, adjuvant chemotherapy was beneficial in the subgroup with NRLN > 21 and RPLN ≤ 0.16 and NRLN ≤ 21 and RPLN > 0.16. CONCLUSION: NRLN > 21 was an independent prognostic factor after ESCC surgery. The combination of NRLN and RPLN may provide a reference for adjuvant chemotherapy use in potential beneficiaries.

4.
J Genet Genomics ; 2024 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-39009302

RESUMEN

China's Northern and Southern Dynasties period (3rd-6th centuries AD) marked a significant era of ethnic integration in northern China. However, previous ancient DNA studies have primarily focused on northern ethnic groups, with limited research on the genetic formation of the hereditary elite family, especially considering their abundant archaeological record and clear material identity. In this study, we obtained the ancient genome of a hereditary elite family, Gao Bin (, 503-572 AD), at 0.6473-fold coverage with 475132 single-nucleotide polymorphisms (SNPs) on the 1240k panel. His mitochondrial haplogroup belonged to Z4 and Y-haplogroup to O1a1a2b-F2444*. The genetic profile of Gao Bin was most similar to that of the northern Han Chinese. He could be modelled as deriving all his ancestry from Late Neolithic to Iron Age Yellow River farmers without influence from Northeast Asia, Korea, or the Mongolian Plateau. Our study sheds light on the genetic formation of hereditary elite families in the context of the Southern and Northern Dynasties ethnic integration.

5.
Langmuir ; 40(28): 14413-14425, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-38946296

RESUMEN

Atmospheric water harvesting (AWH) technology is a new strategy for alleviating freshwater scarcity. Adsorbent materials with high hygroscopicity and high photothermal conversion efficiency are the key to AWH technology. Hence, in this study, a simple and large-scale preparation for a hygroscopic compound of polyurethane (PU) sponge-grafted calcium alginate (CA) with carbon ink (SCAC) was developed. The PU sponge in the SCAC aerogel acts as a substrate, CA as a moisture adsorber, and carbon ink as a light adsorber. The SCAC aerogel exhibits excellent water absorption of 0.555-1.40 g·g-1 within a wide range of relative humidity (40-80%) at 25 °C. The SCAC aerogel could release adsorbed water driven by solar energy, and more than 92.17% of the adsorbed water could be rapidly released over a wide solar intensity range of 1.0-2.0 sun. In an outdoor experiment, 57.517 g of SCAC was able to collect 32.8 g of clean water in 6 h, and the water quality meets the drinking water standards set by the World Health Organization. This study suggests a new approach to design promising AWH materials and infers the potential practical application of SCAC aerogel-based adsorbents.

6.
J Colloid Interface Sci ; 674: 913-924, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38959737

RESUMEN

Rational design and preparation of a multiphase electrocatalyst for hydrogen evolution reaction (HER) has become a hot research topic, while applicable and pH versatility of vanadium tetrasulfide (VS4) and heptairon octasulfide (Fe7S8) composites have rarely been reported. Here, the facile topological sulfide self-template sacrifice method using FeV bimetallic MOFs is designed to obtain Fe7S8 coupled with VS4 heterostructures, enhancing the electron precipitation in the catalysts and attracts electrons to migrate. According to DFT simulations, the electronic coupling at the atomic orbital level and the modulation of interfacial electrons among various interfaces play a crucial role in enhancing the intermediate state process of the hydrogen evolution reaction (HER) across the entire pH range, promoting the optimal d-band centroid value (εd). Reassuringly, the prepared 3D Fe7S8/VS4 electrodes possessed excellent performances of η10 = 53 mV, η10 = 135 mV and η10 = 38 mV in a conventional three-electrode configuration in a 1 M KOH, 1 M Na2SO4, and 0.5 M H2SO4, and the stabilized currents can all be maintained for 48 h. This innovative design of in situ heterostructured materials constructed from dual transition metal sulfides provides inspiring ideas for the preparation of all-pH catalysts.

7.
Biomed Pharmacother ; 177: 116999, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38925021

RESUMEN

Immune-related adverse events, particularly colitis (irAE-colitis), are significant impediments to the advancement of immune checkpoint therapy. To address this, blocking TNF-α and modulating gut microbiota are effective strategies. However, their precise roles in irAE-colitis pathogenesis and potential reciprocal relationship remain unclear. An irAE-colitis model was established to evaluate the toxicity of DICB and the efficacy of Infliximab, validated through a tumor irAE-colitis mice model. Co-administration of Infliximab with DICB mitigates colitis and enhances efficacy. Analysis of fecal samples from mice reveals altered gut microbiota composition and function induced by irAE-colitis, restored by Infliximab. Notably, Bacteriodes abundance is significantly higher in irAE-colitis. Disruption of arachidonic acid and tyrosine metabolism, and steroid hormone biosynthesis is evident. Mechanistically, a regenerative feedback loop involving DICB, TNF-α and gut microbiota underlies irAE-colitis pathogenesis. In conclusion, Infliximab shows therapeutic effects against DICB toxicity, highlighting the unforeseen roles of gut microbiota and TNF-α in irAE-colitis.

8.
Molecules ; 29(11)2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38893286

RESUMEN

An iodophor-catalyzed direct disulfenylation of amino naphthalenes with aryl sulfonyl hydrazines in water was developed. A series of aryl sulfides were obtained in moderate to excellent yields. The advantages of this green protocol were the simple reaction conditions (metal-free, water as the solvent, under air), the odorless and easily available sulfur reagent, the broad substrate scope, and gram-scale synthesis. Moreover, the potential application of aryl sulfides was exemplified by further transformations.

9.
Sci Rep ; 14(1): 13997, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38886202

RESUMEN

Efficient seawater desalination is an effective way to solve the shortages of fresh water and energy but with limitations of the low fresh water production rate and high cost. Here, a hollow carbon fiber (HCF) wrapped by regular reduced graphene oxide (rGO) wave-like folds (rGO@HCF) is prepared on account of the differences in thermal shrinkage performance between graphene oxide (GO) and willow catkins fiber. Under one sun irradiation (1 kW m-2), the dry and wet surface temperature of the resulting evaporator reached up to 119.1 °C and 61.7 °C, respectively, and the water steam production rate reached 3.42 kg m-2 h-1. Also, for the outdoor experiment, the rGO@HCF exhibits good evaporator performance which reach up 27.8 kg m-2 day-1. Additionally, rGO@HCF also shows good seawater desalination performance and excellent durability for longtime work. DSC results indicate that the evaporation enthalpy of bulk water and adsorbed water decreased from 2503.92 to 1020.54 J g-1. The excellent evaporating performance is mainly attributed to the regular wave-like microstructure surface of the HCF, which can enhance the light absorption, reduced the vaporization enthalpy of the adsorption water. The findings not only introduce a novel approach for agricultural utilization, but also establish a crucial theoretical foundation for the design of regular wave-like microstructures.

10.
Front Pharmacol ; 15: 1256992, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38915475

RESUMEN

Purpose: Metastatic non-small cell lung cancer (mNSCLC) has a high incidence rate, and economic burdens to patients, healthcare systems, and societies. Durvalumab plus tremelimumab and chemotherapy (T+D+CT) is a novel therapeutic strategy for mNSCLC, which demonstrated promising efficacy in a phase-3 randomized clinical trial, but its economic value remains unclear. Methods: This economic evaluation used a hypothetical cohort of patients with mNSCLC, with characteristics mirroring those of the participants in the POSEIDON trial. Several partitioned survival models were constructed to estimate 15-year costs and health outcomes associated with the T+D+CT, durvalumab plus chemotherapy (D+CT) and chemotherapy alone (CT) strategies, discounting costs and effectiveness at 3% annually. Costs were in 2023 US dollars. Data were derived from the POSEIDON trial and published literature. Deterministic and probabilistic sensitivity analyses were performed to assess the uncertainty of input parameters and study generalizability. The analysis was designed and conducted from September 2022 to March 2023. To evaluate the cost-effectiveness of T+D+CT, compared with CT and D+CT, for mNSCLC from the perspectives of the US healthcare sector and society. Findings: From the healthcare sector's perspective, the T+D+CT yielded an additional 0.09 QALYs at an increased cost of $7,108 compared with CT, which resulted in an ICER of $82,501/QALY. The T+D+CT strategy yielded an additional 0.02 QALYs at an increased cost of $27,779 compared with the D+CT, which resulted in an ICER of $1,243,868/QALY. The economic results of T+D+CT vs. CT were most sensitive to the annual discount rate, subsequent immunotherapy cost, tremelimumab cost, palliative care and death cost, pemetrexed cost, and durvalumab cost. The T+D+CT strategy was considered cost-effective relative to CT in 59%-82% of model iterations against willingness-to-pay. thresholds of $100,000/QALY gained to $150,000/QALY gained. From the societal perspective, the T+D+CT can be considered as cost-effective as compared with CT or D+CT, independent of histology. Implications: In this cost-effectiveness analysis, the T+D+CT strategy represented good value compared with CT for patients with mNSCLC from the perspectives of the healthcare sector and the society. This treatment strategy may be prioritized for mNSCLC patients at high risks of disease progression.

11.
Value Health Reg Issues ; 43: 101001, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38850589

RESUMEN

OBJECTIVES: Assess hospital healthcare resource utilization (HCRU) and associated hospital costs of patients with lupus nephritis (LN) in China and compare these outcomes with a systemic lupus erythematosus (SLE) cohort (SLE with/without LN) as well as exploring the effect of end-stage kidney disease (ESKD). METHODS: This retrospective administrative claims-based analysis identified patients with SLE and SLE with LN from China using diagnosis codes and keywords. Patients with LN were subcategorized by presence of ESKD. Outcomes included all-cause and disease-specific HCRU (defined as healthcare visits including inpatient and outpatient visits) and medical costs (in 2022 US dollars). RESULTS: In total, 3645 patients with SLE were included, of whom 404 (11%) had LN. Among those with LN, 142 (35%) had ESKD. Median (interquartile range) all-cause healthcare visits per patient per month (PPPM) was significantly greater for patients with LN (2.08 [4.01]) vs SLE (0.92 [1.64]; P < .0001). Patients with LN and ESKD (3.00 [4.18]) had numerically more all-cause healthcare visits PPPM compared with LN patients without ESKD (1.50 [3.45]). Median all-cause costs PPPM were significantly greater among patients with LN ($287.46 [477.15]) vs SLE ($113.09 [267.39]; P < .0001) and numerically higher for patients with LN and ESKD ($466.29 [958.90]) vs LN without ESKD ($223.50 [319.56]). CONCLUSIONS: Chinese patients with LN had greater HCRU and hospital healthcare costs compared with the general SLE cohort. This burden was higher for those with ESKD. These data highlight the substantial HCRU among patients with LN in China, especially those with ESKD, suggesting the need for early diagnosis and timely management of LN to mitigate the economic burden.

12.
Top Curr Chem (Cham) ; 382(2): 20, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38829467

RESUMEN

Cannabis sativa has long been used for neurological and psychological healing. Recently, cannabidiol (CBD) extracted from cannabis sativa has gained prominence in the medical field due to its non-psychotropic therapeutic effects on the central and peripheral nervous systems. CBD, also acting as a potent antioxidant, displays diverse clinical properties such as anticancer, antiinflammatory, antidepressant, antioxidant, antiemetic, anxiolytic, antiepileptic, and antipsychotic effects. In this review, we summarized the structural activity relationship of CBD with different receptors by both experimental and computational techniques and investigated the mechanism of interaction between related receptors and CBD. The discovery of structural activity relationship between CBD and target receptors would provide a direction to optimize the scaffold of CBD and its derivatives, which would give potential medical applications on CBD-based therapies in various illnesses.


Asunto(s)
Cannabidiol , Cannabidiol/química , Cannabidiol/farmacología , Cannabidiol/metabolismo , Humanos , Animales , Antioxidantes/química , Antioxidantes/farmacología , Cannabis/química , Relación Estructura-Actividad , Receptores de Cannabinoides/metabolismo , Anticonvulsivantes/química , Anticonvulsivantes/farmacología , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antidepresivos/química , Antidepresivos/farmacología
13.
Risk Manag Healthc Policy ; 17: 1375-1385, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38813068

RESUMEN

Background: Although affordable generics could probably contribute to the solution of rapidly increasing pharmaceutical expenditure, those drugs are prescribed at a lower rate in China. Physicians' perception and knowledge of generics have a great influence on their prescribing behavior. Objective: This study aimed to identify factors that affect physicians' generic prescribing behavior based on the theory of planned behaviors (TPB). Methods: Data were collected by both electronic and paper-based surveys from 1297 Chinese physicians, and 1047 surveys were retained. The structural equation model (SEM) was employed to investigate the relationship between four behavioral constructs, namely, attitudes, subjective norms, perceived control of behaviors, and intentions. Results: About 50% of Chinese physicians had a positive attitude towards generic drugs that had passed the "Consistency Evaluation of Quality and Efficacy of Generic Drugs" (high-quality generic drugs), but their knowledge of generic drugs was relatively inadequate. The path coefficients for the effect of attitudes, subjective norms, and perceived behavioral control on behavioral intention were 0.285, 0.366, and 0.322 respectively. The path coefficients for the effect of behavioral intention and perceived behavioral control on prescribing behavior were 0.009 and 0.410 respectively. Conclusion: Physicians' attitudes, subjective norms, and perceived behavioral control were significant positive correlation predictors of behavioral intention. Subjective norms and perceived behavior control had a greater impact than attitude on physicians' prescribing intention. However, the generic prescribing behavior is not under the volitional control of Chinese physicians. Physicians' prescribing practice is likely affected by perceived strong control over prescribing generic drugs.

14.
J Colloid Interface Sci ; 671: 15-33, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38788421

RESUMEN

The exploration of bifunctional electrocatalysts with high activity, stability, and economy is of great significance in promoting the development of water splitting. Herein, a dual active sites heterostructure NiCoS/NC was designed to be derived in situ on 3D N-doped porous carbon (NC) using gelatin as a nitrogen and carbon source. The characterization of experiments suggests that nanoflower-like Ni2CoS4 (abbreviated as NiCoS) was randomly distributed on the NC substrate, and the sheet-like NC formed a highly open porous network structure resembling a honeycomb, which provided more accessible active sites for electrolyte ions. In addition, the special nanostructures of the catalyst materials help to promote the surface reconstruction to the real active substance NiOOH/CoOOH, and the double active sites synergistically reduce the overpotential of OER and improve its kinetics. DFT (Density-functional theory) calculations reveal the electronic coupling of NiCoS/NC in atomic orbitals, modulation of electrons by the heterointerface and N-doping, and synergistic effect of dual active sites improving the inherent catalytic activity. The NiCoS/NC composite electrocatalyst exhibited a 177 mV small OER overpotential and a 132 mV small HER overpotential with Faraday efficiencies as high as 96 % and 98 % at 10 mA cm-2 current density. In the two-electrode system, it also requires only an ultra-low voltage of 1.52 V to achieve a 10 mA cm-2 current density, and it shows excellent long-term water splitting stability. This provides a new idea for the development of transition metal-based bifunctional electrocatalysts.

15.
Sensors (Basel) ; 24(9)2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38733011

RESUMEN

Demand is strong for sensitive, reliable, and cost-effective diagnostic tools for cancer detection. Accordingly, bead-based biosensors have emerged in recent years as promising diagnostic platforms based on wide-ranging cancer biomarkers owing to the versatility, high sensitivity, and flexibility to perform the multiplexing of beads. This comprehensive review highlights recent trends and innovations in the development of bead-based biosensors for cancer-biomarker detection. We introduce various types of bead-based biosensors such as optical, electrochemical, and magnetic biosensors, along with their respective advantages and limitations. Moreover, the review summarizes the latest advancements, including fabrication techniques, signal-amplification strategies, and integration with microfluidics and nanotechnology. Additionally, the challenges and future perspectives in the field of bead-based biosensors for cancer-biomarker detection are discussed. Understanding these innovations in bead-based biosensors can greatly contribute to improvements in cancer diagnostics, thereby facilitating early detection and personalized treatments.


Asunto(s)
Biomarcadores de Tumor , Técnicas Biosensibles , Neoplasias , Técnicas Biosensibles/métodos , Técnicas Biosensibles/instrumentación , Humanos , Neoplasias/diagnóstico , Biomarcadores de Tumor/análisis , Técnicas Electroquímicas/métodos , Nanotecnología/tendencias , Nanotecnología/métodos , Nanotecnología/instrumentación , Microfluídica/métodos , Microfluídica/instrumentación , Microfluídica/tendencias
16.
Insights Imaging ; 15(1): 119, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38755299

RESUMEN

OBJECTIVE: The study aimed to investigate the predictive value of dynamic contrast-enhanced ultrasound (DCE-US) in differentiating small-duct (SD) and large-duct (LD) types of intrahepatic cholangiocarcinoma (ICC). METHODS: This study retrospectively enrolled 110 patients with pathologically confirmed ICC lesions who were subject to preoperative contrast-enhanced ultrasound (CEUS) examinations between January 2022 and February 2023. Patients were further classified according to the subtype: SD-type and LD-type, and an optimal predictive model was established and validated using the above pilot cohort. The test cohort, consisting of 48 patients prospectively enrolled from March 2023 to September 2023, was evaluated. RESULTS: In the pilot cohort, compared with SD-type ICCs, more LD-type ICCs showed elevated carcinoembryonic antigen (p < 0.001), carbohydrate antigen 19-9 (p = 0.004), ill-defined margin (p = 0.018), intrahepatic bile duct dilation (p < 0.001). Among DCE-US quantitative parameters, the wash-out area under the curve (WoAUC), wash-in and wash-out area under the curve (WiWoAUC), and fall time (FT) at the margin of lesions were higher in the SD-type group (all p < 0.05). Meanwhile, the mean transit time (mTT) and wash-out rate (WoR) at the margin of the lesion were higher in the LD-type group (p = 0.041 and 0.007, respectively). Logistic regression analysis showed that intrahepatic bile duct dilation, mTT, and WoR were significant predictive factors for predicting ICC subtypes, and the AUC of the predictive model achieved 0.833 in the test cohort. CONCLUSIONS: Preoperative DCE-US has the potential to become a novel complementary method for predicting the pathological subtype of ICC. CRITICAL RELEVANCE STATEMENT: DCE-US has the potential to assess the subtypes of ICC lesions quantitatively and preoperatively, which allows for more accurate and objective differential diagnoses, and more appropriate treatments and follow-up or additional examination strategies for the two subtypes. KEY POINTS: Preoperative determination of intrahepatic cholangiocarcinoma (ICC) subtype aids in surgical decision-making. Quantitative parameters from dynamic contrast-enhanced US (DCE-US) allow for the prediction of the ICC subtype. DCE-US-based imaging has the potential to become a novel complementary method for predicting ICC subtypes.

17.
Metabolism ; 155: 155911, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38609037

RESUMEN

BACKGROUND: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing year by year and has become one of the leading causes of end-stage liver disease worldwide. Triggering Receptor Expressed on Myeloid Cells 2 (Trem2) has been confirmed to play an essential role in the progression of MASLD, but its specific mechanism still needs to be clarified. This study aims to explore the role and mechanism of Trem2 in MASLD. METHODS: Human liver tissues were obtained from patients with MASLD and controls. Myeloid-specific knockout mice (Trem2mKO) and myeloid-specific overexpression mice (Trem2TdT) were fed a high-fat diet, either AMLN or CDAHFD, to establish the MASLD model. Relevant signaling molecules were assessed through lipidomics and RNA-seq analyses after that. RESULTS: Trem2 is upregulated in human MASLD/MASH-associated macrophages and is associated with hepatic steatosis and inflammation progression. Hepatic steatosis and inflammatory responses are exacerbated with the knockout of myeloid Trem2 in MASLD mice, while mice overexpressing Trem2 exhibit the opposite phenomenon. Mechanistically, Trem2mKO can aggravate macrophage pyroptosis through the PI3K/AKT signaling pathway and amplify the resulting inflammatory response. At the same time, Trem2 promotes the inflammation resolution phenotype transformation of macrophages through TGFß1, thereby promoting tissue repair. CONCLUSIONS: Myeloid Trem2 ameliorates the progression of Metabolic dysfunction-associated steatotic liver disease by regulating macrophage pyroptosis and inflammation resolution. We believe targeting myeloid Trem2 could represent a potential avenue for treating MASLD.


Asunto(s)
Progresión de la Enfermedad , Hígado Graso , Inflamación , Macrófagos , Glicoproteínas de Membrana , Piroptosis , Receptores Inmunológicos , Animales , Humanos , Masculino , Ratones , Hígado Graso/metabolismo , Hígado Graso/patología , Hígado Graso/genética , Inflamación/metabolismo , Inflamación/patología , Hígado/metabolismo , Hígado/patología , Macrófagos/metabolismo , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Enfermedades Metabólicas/metabolismo , Enfermedades Metabólicas/patología , Enfermedades Metabólicas/genética , Ratones Endogámicos C57BL , Ratones Noqueados , Piroptosis/fisiología , Receptores Inmunológicos/metabolismo , Receptores Inmunológicos/genética
18.
Chemphyschem ; 25(14): e202400052, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38629246

RESUMEN

A new group of BF3 complexing phosphate/phosphonate ionic liquids (ILs) [Emim][X(BF3)2] (X=dimethyl phosphate, diethyl phosphate, methyl phosphonate, and ethyl phosphonate) were synthesized and characterized. Key thermophysical properties of the new complex ionic liquids, including density, viscosity, conductivity, surface tension, solid-liquid phase transition, and thermal stability were determined and compared with those of [Emim][X]. Some other important thermophysical properties such as isobaric thermal expansion coefficient, molecular volume, standard molar entropy, and lattice potential energy were obtained from measured density data, and the free volume was estimated by a linear equation presented in this article, while critical temperature, normal boiling temperature, and enthalpy of vaporization were estimated from measured surface tension and density data. Furthermore, Fragility study shows that [Emim][X(BF3)2] should be considered as fragile liquids, while [Emim][X] could be considered as extremely fragile liquids. The ionicity of [Emim][X(BF3)2] was predicted by Walden rule, and the result shows that these ILs fit well with Walden law. The key features of these complex ILs are their extremely low glass transition (-95.33~-98.46 °C) without melting, considerably low viscosities (33.876~58.117 mPa ⋅ s), and high values of free volume fraction (comparable to [Omim][BF4], [Emim][NTf2], and [Emim][TCB]).

19.
Int J Mol Sci ; 25(7)2024 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-38612440

RESUMEN

Salinity is one of the most serious threats to sustainable agriculture. The Salt Overly Sensitive (SOS) signaling pathway plays an important role in salinity tolerance in plants, and the SOS2 gene plays a critical role in this pathway. Mulberry not only has important economic value but also is an important ecological tree species; however, the roles of the SOS2 gene associated with salt stress have not been reported in mulberry. To gain insight into the response of mulberry to salt stress, SOS2 (designated MulSOS2) was cloned from mulberry (Morus atropurpurea Roxb), and sequence analysis of the amino acids of MulSOS2 showed that it shares some conserved domains with its homologs from other plant species. Our data showed that the MulSOS2 gene was expressed at different levels in different tissues of mulberry, and its expression was induced substantially not only by NaCl but also by ABA. In addition, MulSOS2 was exogenously expressed in Arabidopsis, and the results showed that under salt stress, transgenic MulSOS2 plants accumulated more proline and less malondialdehyde than the wild-type plants and exhibited increased tolerance to salt stress. Moreover, the MulSOS2 gene was transiently overexpressed in mulberry leaves and stably overexpressed in the hairy roots, and similar results were obtained for resistance to salt stress in transgenic mulberry plants. Taken together, the results of this study are helpful to further explore the function of the MulSOS2 gene, which provides a valuable gene for the genetic breeding of salt tolerance in mulberry.


Asunto(s)
Arabidopsis , Morus , Tolerancia a la Sal/genética , Morus/genética , Fitomejoramiento , Estrés Salino , Agricultura , Plantas Modificadas Genéticamente
20.
Zhongguo Zhong Yao Za Zhi ; 49(6): 1683-1689, 2024 Mar.
Artículo en Chino | MEDLINE | ID: mdl-38621952

RESUMEN

The purpose of this study was to evaluate the economics of Annao Pills combined with antihypertensive drugs in the treatment of primary hypertension in the Chinese medical setting. TreeAge pro 2018 was used for cost-effect analysis and sensitivity analysis of the two treatment regimens. The intervention time of the simulation model was 2 weeks. The cost parameters were derived from Yaozhi.com, and the effect parameters were based on Meta-analysis of randomized controlled trial(RCT) involving Annao Pills. The experimental group was treated with Annao Pills combined with anti-hypertensive drugs(nifedipine controlled-release tablets + losartan potassium tablets), and the control group was treated with anti-hypertensive drugs(nifedipine controlled-release tablets + losartan potassium tablets). The basic analysis showed that the incremental cost-effect ratio(ICER) of the two groups was 2 678.67 yuan, which was less than 7.26% of the per capita disposable income in 2022. That is, compared with anti-hypertensive drugs alone, Annao Pills combined with antihypertensive drugs cost 2 678.67 yuan more for each additional patient with primary hypertension. The results of sensitivity analysis verified the robustness of the basic analysis results. The probability sensitivity results showed that when the patient's personal willingness to pay the price was higher than 2 650 yuan, the probability of the regimen in the experimental group was higher, which was consistent with the results of the basic analysis. In conclusion, when the price was higher than 2 650 yuan, Annao Pills combined with anti-hypertensive drugs was more economical than anti-hypertensive drugs alone in terms of improving the response rate of the patients with primary hypertension.


Asunto(s)
Antihipertensivos , Nifedipino , Humanos , Antihipertensivos/uso terapéutico , Análisis Costo-Beneficio , Árboles de Decisión , Preparaciones de Acción Retardada , Hipertensión Esencial , Losartán/uso terapéutico
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