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1.
Trials ; 25(1): 667, 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39385296

RESUMEN

BACKGROUND: Currently, most elderly chronic heart failure (CHF) patients go home for rehabilitation after certain treatment in hospitals. However, the results of their rehabilitation at home are not satisfactory. According to studies, dyadic treatments can increase the efficiency of home rehabilitation, enhance both partners' quality of life, lessen the caregiver's load of care, and alleviate the strain of medical resources. Thus, the aim of our research is to design a study protocol that included elderly CHF patients and their informal caregivers as an intervention unit and to explore the impact of the protocol on their health and physical outcomes. METHODS: This is a prospective randomized controlled trial conducted in a triple-A hospital. In total, 80 elderly CHF patients and informal caregivers (80 dyads) will be recruited with informed consent. Based on the randomized numbers, they are divided into a control group (40 dyads) and an intervention group (40 dyads), subjects in the control group will receive usual care, and subjects in the intervention group will receive a home-based disease management program based on the Theory of Dyadic Illness Management on the basis of the control group. The duration of the intervention is 3 months, and the follow-up is 6 months. Data is collected at enrolment, 3 months after the intervention, and 3 months after the end of the intervention. The primary outcome is patients' quality of life and readmission. Secondary outcomes include patients' self-management behaviors, anxiety, and depression and caregivers' quality of life and care burden. DISCUSSION: This study focuses on whether this home-based disease management program can improve the quality of life of elderly patients with CHF, reduce the readmission rate, enhance their self-management capacity, reduce negative emotions, and reduce the burden of informal caregivers. It can provide a new perspective on home management and cardiac rehabilitation of heart failure disease in the elderly, as well as alleviate problems such as the burden of healthcare resources. TRIAL REGISTRATION: Chinese Clinical Trials Registry ChiCRT2300068026. Registered on 3 February 2023, manuscript Version: 1.0,  https://www.chictr.org.cn/ .


Asunto(s)
Cuidadores , Insuficiencia Cardíaca , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Insuficiencia Cardíaca/psicología , Insuficiencia Cardíaca/terapia , Insuficiencia Cardíaca/rehabilitación , Cuidadores/psicología , Estudios Prospectivos , Anciano , Enfermedad Crónica , Servicios de Atención de Salud a Domicilio , Femenino , Resultado del Tratamiento , Masculino , Manejo de la Enfermedad , China , Factores de Tiempo , Salud Mental , Anciano de 80 o más Años
2.
bioRxiv ; 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39253509

RESUMEN

Achieving ultra-long-term release of hydrophilic drugs over several months remains a significant challenge for existing long-acting injectables (LAIs). Existing platforms, such as in situ forming implants (ISFI), exhibit high burst release due to solvent efflux and microsphere-based approaches lead to rapid drug diffusion due to significant water exchange and large pores. Addressing these challenges, we have developed an injectable platform that, for the first time, achieves ultra-long-term release of hydrophilic drugs for over six months. This system employs a methacrylated ultra-low molecular weight pre-polymer (polycaprolactone) to create in situ cross-linked depots (ISCD). The ISCD's solvent-free design and dense mesh network, both attributed to the ultra-low molecular weight of the pre-polymer, effectively minimizes burst release and water influx/efflux. In vivo studies in rats demonstrate that ISCD outperforms ISFI by achieving lower burst release and prolonged drug release. We demonstrated the versatility of ISCD by showcasing ultra-long-term delivery of several hydrophilic drugs, including antiretrovirals (tenofovir alafenamide, emtricitabine, abacavir, and lamivudine), antibiotics (vancomycin and amoxicillin) and an opioid antagonist naltrexone. Additionally, ISCD achieved ultra-long-term release of the hydrophobic drug tacrolimus and enabled co-delivery of hydrophilic drug combinations encapsulated in a single depot. We also identified design parameters to tailor the polymer network, tuning drug release kinetics and ISCD degradation. Pharmacokinetic modeling predicted over six months of drug release in humans, significantly surpassing the one-month standard achievable for hydrophilic drugs with existing LAIs. The platform's biodegradability, retrievability, and biocompatibility further underscore its potential for improving treatment adherence in chronic conditions.

3.
Angew Chem Int Ed Engl ; : e202413913, 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39318265

RESUMEN

Exciton binding energy (Eb) is a key parameter to determine the mechanism and performance of organic optoelectronic devices. Small Eb benefits to reduce the interfacial energy offset and the energy loss of organic solar cells. However, quantum-chemical calculations of the Eb in solid state with considering electronic polarization effects are extremely time-consuming. Furthermore, current studies lack critical descriptors. Here, we use data-driven machine learning (ML) to accelerate the computation and identify the key descriptors most relevant to the solid-state Eb. The results verify two key descriptors associated with molecular and aggregation-state properties for efficient prediction of the solid-state Eb. Moreover, a very high accuracy is achieved by using the extreme gradient boosting algorithm, with the Pearson's correlation coefficient of 0.92. Finally, we use this ML model to predict the Eb of thin films, which is difficult to achieve using the current quantum-chemical calculations due to the large structural disorder. Remarkably, the predicted thin-film Eb values are fully consistent with the results of temperature-dependent photoluminescence spectra. Therefore, our work provides an accurate and efficient approach to predict the solid-state Eb and would be helpful to accelerate the exploitation of novel promising organic photovoltaic materials.

5.
Huan Jing Ke Xue ; 45(8): 4432-4439, 2024 Aug 08.
Artículo en Chino | MEDLINE | ID: mdl-39168663

RESUMEN

Satellite-based formaldehyde(HCHO)columns and tropospheric nitrogen dioxide columns were observed using the Ozone Monitoring Instrument(OMI),and groundbased observations of ozone(O3)for May-August from 2013 to 2022 were connected to calculate the threshold values of the HCHO to NO2 ratio(FNR)in Shanxi Province. Then,the spatiotemporal distributions and variations in summertime ozone photochemical production regimes were analyzed. The results showed that:① The volatile organic compound(VOC) -sensitive regime area(FNR < 2.3)was obviously reduced,while the VOCs-NOx transitional regime(FNR between 2.3-4.1)area increased in the early years and then decreased, and NO x -sensitive regime area expanded significantly in summer from 2013 to 2022 over Shanxi Province. ② The increased summertime FNR during 2013 to 2019 was associated with the co-effect of increased HCHO columns and decreased tropospheric NO2 columns. The Shanxi Province was generally under an NOx regime since 2016,which reflected the remarkable effect of NO x emission reductions;however,there was a shift from a VOC-sensitive regime to a VOCs-NOx transitional regime,in which O3 pollution aggravation was widespread under the background of decreased NOx emissions. The decrease in O3 concentration during 2020 to 2022 followed the synergistical declines in HCHO columns and tropospheric NO2 columns. ③ The O3 weekend effects were reversed in Linfen and Yuncheng but were persistent in the other nine cities. Satellite-based weekend HCHO and NO2 levels were higher than those on weekdays in some cities of Shanxi Province,indicating that the O3 weekend effect was not only dependent on the changes of precursors emissions but was also closely related to O3 photochemical production sensitivity. The results indicated the necessity of simultaneous controls in NOx emissions and VOCs emissions for ozone abatement plans over Shanxi Province. In addition,Taiyuan,Yangquan,Yuncheng,and Jincheng should continue to promote reduction in NOx emissions.

6.
J Hazard Mater ; 478: 135534, 2024 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-39151359

RESUMEN

Cigarette butts have become one of the most common and persistent forms of debris in marine coastal areas, where they pose significant toxicity risks. This study investigated cigarette butt pollution along beaches of the Yellow Sea and used laboratory experiments to assess the toxicity of their leachate and fibers on the euryhaline rotifer Brachionus plicatilis. A pollution index confirmed pollution by this debris across all eight beaches surveyed, where the density of cigarette butts averaged 0.23 butts/m2. In controlled laboratory experiments, both the fibers and leachates from cigarette butts exhibited negative impacts on the development, reproduction, and population growth of rotifers. Unique abnormalities observed under different exposure treatments indicated toxicity specific to certain chemicals and particles. Continuous exposure to cigarette butts initially reduced rotifer fecundity, but this effect diminished over successive generations. However, the exposure induced transgenerational reproductive toxicity in the rotifers. Adaptive responses in rotifers after repeated exposure led to relative reduction in reproductive inhibition in the F3 and F4 generations. Furthermore, rotifers were capable of ingesting and accumulating cigarette butts, and maternal transfer emerged as an alternative pathway for uptake of this material in the offspring. These results increase our understanding of the ecological risks posed by cigarette butts in aquatic environments.


Asunto(s)
Microplásticos , Reproducción , Rotíferos , Contaminantes Químicos del Agua , Animales , Rotíferos/efectos de los fármacos , Reproducción/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/análisis , Microplásticos/toxicidad , Productos de Tabaco/toxicidad , Monitoreo del Ambiente
7.
Cell ; 187(18): 5064-5080.e14, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39089254

RESUMEN

So far, biocomputation strictly follows traditional design principles of digital electronics, which could reach their limits when assembling gene circuits of higher complexity. Here, by creating genetic variants of tristate buffers instead of using conventional logic gates as basic signal processing units, we introduce a tristate-based logic synthesis (TriLoS) framework for resource-efficient design of multi-layered gene networks capable of performing complex Boolean calculus within single-cell populations. This sets the stage for simple, modular, and low-interference mapping of various arithmetic logics of interest and an effectively enlarged engineering space within single cells. We not only construct computational gene networks running full adder and full subtractor operations at a cellular level but also describe a treatment paradigm building on programmable cell-based therapeutics, allowing for adjustable and disease-specific drug secretion logics in vivo. This work could foster the evolution of modern biocomputers to progress toward unexplored applications in precision medicine.


Asunto(s)
Redes Reguladoras de Genes , Humanos , Lógica , Biología Sintética/métodos , Ingeniería Genética/métodos , Biología Computacional/métodos , Animales
8.
ACS Appl Mater Interfaces ; 16(24): 31648-31656, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38837705

RESUMEN

Utilizing aluminum-doped nano LLZO (Li6.28La3Zr2Al0.24O12) as the ceramic filler, we synthesized and optimized LLZO/PVDF/LiClO4 composite polymer electrolytes (CPEs) to achieve high ionic conductivity and good interfacial stability with metallic lithium. The research examines how the PVDF grade and the mass ratio of PVDF to LiClO4 affect the ionic conductivity, lithium metal compatibility, and overall performance of CPEs. The CPE using Kynar PVDF 741 and a PVDF-to-LiClO4 mass ratio of 2:1 emerged as superior, displaying a high ionic conductivity at room temperature (0.12 mS/cm), the lowest activation energy (0.247 eV), an extensive electrochemical stability window (approximately 4.9 V), and robust mechanical strength. In tests with lithium metal symmetric cells, the membrane facilitated over 1000 h of stable cycling at 0.1 mA cm-2 and 0.1 mAh cm-2. Furthermore, when integrated into full solid-state lithium-metal batteries with LiFePO4 cathodes, it sustained more than 80% capacity retention across 500 charge/discharge cycles at a rate of 0.5 C with constantly high Coulombic efficiencies above 99.8%, underscoring its exceptional durability and efficiency. This research provides a practical framework and benchmarks for developing LLZO/PVDF-based CPEs with high ionic conductivity and enhanced stability against lithium metals.

9.
Nat Commun ; 15(1): 4315, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38773104

RESUMEN

To enable high performance of all solid-state batteries, a catholyte should demonstrate high ionic conductivity, good compressibility and oxidative stability. Here, a LaCl3-based Na+ superionic conductor (Na1-xZrxLa1-xCl4) with high ionic conductivity of 2.9 × 10-4 S cm-1 (30 °C), good compressibility and high oxidative potential (3.80 V vs. Na2Sn) is prepared via solid state reaction combining mechanochemical method. X-ray diffraction reveals a hexagonal structure (P63/m) of Na1-xZrxLa1-xCl4, with Na+ ions forming a one-dimensional diffusion channel along the c-axis. First-principle calculations combining with X-ray absorption fine structure characterization etc. reveal that the ionic conductivity of Na1-xZrxLa1-xCl4 is mainly determined by the size of Na+-channels and the Na+/La3+ mixing in the one-dimensional diffusion channels. When applied as a catholyte, the NaCrO2||Na0.7Zr0.3La0.7Cl4||Na3PS4||Na2Sn all-solid-state batteries demonstrate an initial capacity of 114 mA h g-1 and 88% retention after 70 cycles at 0.3 C. In addition, a high capacity of 94 mA h g-1 can be maintained at 1 C current density.

10.
Clin Res Hepatol Gastroenterol ; 48(6): 102372, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38719145

RESUMEN

OBJECTIVE: WeChat-based nursing interventions alleviate mental distress. This study intended to investigate the effect of WeChat online education and care (WOEC) on the mental health of caregivers and the satisfaction of elderly postoperative colorectal cancer (CRC) patients. METHODS: In total, 92 elderly postoperative CRC patients and 92 caregivers were randomly separated into the WOEC group (46 patients and 46 caregivers) and the control care group (46 patients and 46 caregivers). Caregivers received corresponding intervention for 8 weeks. Beck depression inventory (BDI) and beck anxiety inventory (BAI) of caregivers, and self-report satisfaction (SRS) of patients were assessed. RESULTS: In caregivers, BDI scores at 8 weeks after enrollment (W8) (P = 0.024) and BAI score at W8 (P = 0.009), depression severity at W8 (P = 0.036), as well as anxiety severity at 4 weeks after enrollment (W4) (P = 0.028) and W8 (P = 0.047) were declined in the WOEC group versus the control care group. Regarding patients, SRS scores at W4 (P = 0.044) and W8 (P = 0.025), the satisfaction degree at W4 (P = 0.033) and W8 (P = 0.034), as well as the satisfied and very satisfied rates at W4 (P = 0.031) and W8 (P = 0.029) were elevated in the WOEC group versus the control care group. By subgroup analyses, WOEC exhibited favorable effects on reducing mental stress in caregivers of patients with eastern cooperative oncology group performance status at enrollment <3, and in caregivers with an education level of high school & university and above. CONCLUSION: WOEC effectively relieves mental stress in caregivers of elderly postoperative CRC patients, and also elevates satisfaction in these patients.


Asunto(s)
Cuidadores , Neoplasias Colorrectales , Humanos , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/psicología , Cuidadores/educación , Cuidadores/psicología , Masculino , Femenino , Anciano , Persona de Mediana Edad , Satisfacción del Paciente , Distrés Psicológico , Depresión/etiología , Estrés Psicológico/etiología , Ansiedad/prevención & control , Ansiedad/etiología , Educación a Distancia , Satisfacción Personal
11.
Ecol Evol ; 14(4): e11307, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38665893

RESUMEN

Global warming has raised concerns regarding the potential impact on aquatic biosafety and health. To illuminate the adaptive mechanisms of bdelloid rotifers in response to global warming, the ecological and transcriptomic characteristics of two strains (HX and ZJ) of Rotaria rotatoria were investigated at 25°C and 35°C. Our results showed an obvious genetic divergence between the two geographic populations. Thermal stress significantly reduced the average lifespan of R. rotatoria in both strains, but increased the offspring production in the ZJ strain. Furthermore, the expression levels of genes Hsp70 were significantly upregulated in the HX strain, while GSTo1 and Cu/Zn-SOD were on the contrary. In the ZJ strain, the expression levels of genes Hsp70, CAT2, and GSTo1 were upregulated under thermal stress. Conversely, a significant decrease in the expression level of the Mn-SOD gene was observed in the ZJ strain under thermal stress. Transcriptomic profiling analysis revealed a total of 105 and 5288 differentially expressed genes (DEGs) in the HX and ZJ strains under thermal stress, respectively. The PCA results showed clear differences in gene expression pattern between HX and ZJ strains under thermal stress. Interestingly, compared to the HX strain, numerous downregulated DEGs in the ZJ strain were enriched into pathways related to metabolism under thermal stress, suggesting that rotifers from the ZJ strain prioritize resource allocation to reproduction by suppressing costly metabolic processes. This finding is consistent with the life table results. This study provides new insights into the adaptive evolution of aquatic animals in the context of global climate change.

12.
Nat Commun ; 15(1): 2740, 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38548733

RESUMEN

Photoreceptor proteins utilise chromophores to sense light and trigger a biological response. The discovery that adenosylcobalamin (or coenzyme B12) can act as a light-sensing chromophore heralded a new field of B12-photobiology. Although microbial genome analysis indicates that photoactive B12-binding domains form part of more complex protein architectures, regulating a range of molecular-cellular functions in response to light, experimental evidence is lacking. Here we identify and characterise a sub-family of multi-centre photoreceptors, termed photocobilins, that use B12 and biliverdin (BV) to sense light across the visible spectrum. Crystal structures reveal close juxtaposition of the B12 and BV chromophores, an arrangement that facilitates optical coupling. Light-triggered conversion of the B12 affects quaternary structure, in turn leading to light-activation of associated enzyme domains. The apparent widespread nature of photocobilins implies involvement in light regulation of a wider array of biochemical processes, and thus expands the scope for B12 photobiology. Their characterisation provides inspiration for the design of broad-spectrum optogenetic tools and next generation bio-photocatalysts.


Asunto(s)
Pigmentos Biliares , Fotorreceptores Microbianos , Fotoquímica , Biliverdina , Proteínas Bacterianas/metabolismo , Fotorreceptores Microbianos/química , Luz
13.
MedComm (2020) ; 5(3): e483, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38463398

RESUMEN

Epidermal growth factor receptor-targeted (EGFR-targeted) therapies show promise for non-small cell lung cancer (NSCLC), but they are ineffective in a third of patients who lack EGFR mutations. This underlines the need for personalized treatments for patients with EGFR wild-type NSCLC. A genome-wide CRISPR/Cas9 screen has identified the enzyme phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS), which is vital in de novo purine biosynthesis and tumor development, as a potential drug target for EGFR wild-type NSCLC. We have further confirmed that PAICS expression is significantly increased in NSCLC tissues and correlates with poor patient prognosis. Knockdown of PAICS resulted in a marked reduction in both in vitro and in vivo proliferation of EGFR wild-type NSCLC cells. Additionally, PAICS silencing led to cell-cycle arrest in these cells, with genes involved in the cell cycle pathway being differentially expressed. Consistently, an increase in cell proliferation ability and colony number was observed in cells with upregulated PAICS in EGFR wild-type NSCLC. PAICS silencing also caused DNA damage and cell-cycle arrest by interacting with DNA repair genes. Moreover, decreased IMPDH2 activity and activated PI3K-AKT signaling were observed in NSCLC cells with EGFR mutations, which may compromise the effectiveness of PAICS knockdown. Therefore, PAICS plays an oncogenic role in EGFR wild-type NSCLC and represents a potential therapeutic target for this disease.

14.
ACS Appl Mater Interfaces ; 16(6): 7327-7337, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38299338

RESUMEN

A 3D host design for lithium (Li)-metal anodes can effectively accommodate volume changes and suppress Li dendrite growth; nonetheless, its practical applicability in energy-dense Li-metal batteries (LMBs) is plagued by excessive Li loading. Herein, we introduced eco- and human-friendly Se seeds into 3D carbon cloth (CC) to create a robust host for efficient Li deposition/stripping. The highly lithiophilic nano-Se endowed the Se-decorated CC (Se@CC) with perfect Li wettability for instantaneous Li infusion. At an optimal Li loading of 17 mg, the electrode delivered an unprecedentedly long life span of 5400 h with low overpotentials <36 mV at 1 mA cm-2/1 mAh cm-2 and 1500 h at 5 mA cm-2/5 mAh cm-2. Furthermore, the uniform Se distribution and strong Li-Se binding allowed for further reduction in Li loading to 2 mg via direct Li electrodeposition. The corresponding LiNi0.8Co0.1Mn0.1O2 (NCM811)-based full cell afforded a high capacity retention rate of 74.67% over 300 cycles at a low N/P ratio of 8.64. Finally, the initial anode-free LMB using a NCM811 cathode and a Se@CC anode current collector demonstrated a high electrode-level specific energy of 531 Wh kg-1 and consistently high CEs >99.7% over 200 cycles. This work highlights a high-performance host design with excellent tunability for practical high-energy-density LMBs.

15.
Org Lett ; 26(5): 1028-1033, 2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38285509

RESUMEN

A series of sila-annulated phenanthrene imides were synthesized through a three-step synthetic route, which represent a hybrid class of biphenyl-based π-conjugated molecules incorporating an imide unit and silole. A comprehensive investigation of their structural, photophysical, and electronic properties was studied by experiment and theoretical calculations. Notably, sila-annulated phenanthrene imides with significant aggregation-induced emission (AIE) properties were observed.

16.
Cell Res ; 34(1): 31-46, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38172533

RESUMEN

Here, we present a gene regulation strategy enabling programmable control over eukaryotic translational initiation. By excising the natural poly-adenylation (poly-A) signal of target genes and replacing it with a synthetic control region harboring RNA-binding protein (RBP)-specific aptamers, cap-dependent translation is rendered exclusively dependent on synthetic translation initiation factors (STIFs) containing different RBPs engineered to conditionally associate with different eIF4F-binding proteins (eIFBPs). This modular design framework facilitates the engineering of various gene switches and intracellular sensors responding to many user-defined trigger signals of interest, demonstrating tightly controlled, rapid and reversible regulation of transgene expression in mammalian cells as well as compatibility with various clinically applicable delivery routes of in vivo gene therapy. Therapeutic efficacy was demonstrated in two animal models. To exemplify disease treatments that require on-demand drug secretion, we show that a custom-designed gene switch triggered by the FDA-approved drug grazoprevir can effectively control insulin expression and restore glucose homeostasis in diabetic mice. For diseases that require instantaneous sense-and-response treatment programs, we create highly specific sensors for various subcellularly (mis)localized protein markers (such as cancer-related fusion proteins) and show that translation-based protein sensors can be used either alone or in combination with other cell-state classification strategies to create therapeutic biocomputers driving self-sufficient elimination of tumor cells in mice. This design strategy demonstrates unprecedented flexibility for translational regulation and could form the basis for a novel class of programmable gene therapies in vivo.


Asunto(s)
Diabetes Mellitus Experimental , Animales , Ratones , Factor 4F Eucariótico de Iniciación/metabolismo , Procesamiento Proteico-Postraduccional , Regulación de la Expresión Génica , Proteínas Portadoras/metabolismo , Mamíferos
17.
Chemistry ; 30(21): e202304149, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38189550

RESUMEN

Aqueous Zn-metal batteries (AZMBs) hold a promise as the next-generation energy storage devices due to their low cost and high specific energy. However, the actual energy density falls far below the requirements of commercial AZMBs due to the use of excessive Zn as anode and the associated issues including dendritic growth and side reactions. Reducing the N/P ratio (negative capacity/positive capacity) is an effective approach to achieve high energy density. A significant amount of research has been devoted to increasing the cathode loading and specific capacity or tuning the Zn anode utilization to achieve low N/P ratio batteries. Nevertheless, there is currently a lack of comprehensive overview regarding how to enhance the utilization of the Zn anode to balance the cycle life and energy density of AZMBs. In this review, we summarize the challenges faced in achieving high-utilization Zn anodes and elaborate on the modifying strategies for the Zn anode to lower the N/P ratio. The current research status and future prospects for the practical application of high-performance AZMBs are proposed at the end of the review.

18.
Clin Pharmacol Ther ; 115(5): 993-1006, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38037868

RESUMEN

Circulating tumor DNA (ctDNA) analysis increasingly provides a promising minimally invasive alternative to tissue biopsies in precision oncology. However, there are no ctDNA analysis approaches available in nasopharyngeal carcinoma (NPC) and current methods of ctDNA mutation profiling have limited resolution because of the high background noise and false-positive rate caused by benign variants in plasma cell-free DNA (cfDNA), majorly generated during clonal hematopoiesis. Although personalized parallel white blood cell genome sequencing suppresses the noise of clonal hematopoiesis variances, the system cost and complexity restrict its extensive application in clinical settings. We developed Matched WBC Genome sequencing Independent CtDNA profiling (MaGIC) approaches, which synergically integrated a ctDNA capturing panel for a hybrid capture cfDNA deep sequencing, in silico background elimination, and a reliable readout measurement. We profiled the ctDNAs of 80 plasma samples from 40 patients with NPC before and during chemotherapy by MaGICs. In addition, the public cfDNA sequencing data and The Cancer Genome Atlas project data were analyzed by MaGICs to evaluate their application in other scenarios of patient classification. The MaGIC version-2 has the ability to predict the chemosensitivity of patients with NPC with high accuracy by utilizing a single sample of liquid biopsy from each patient prior to a standardized treatment regimen. Moreover, both versions of MaGICs are of ideal performance in the diagnosis of patients with prostate cancer by liquid biopsy and prognosis prediction of multiple cancers by tissue biopsy. This study has the potential to enhance the sensitivity and expand the application scope of ctDNA detection, independently of other paired genome sequencing methods. As a result, it might further increase the clinical utilization of liquid biopsy based on ctDNA.


Asunto(s)
ADN Tumoral Circulante , Neoplasias Nasofaríngeas , Neoplasias de la Próstata , Masculino , Humanos , ADN Tumoral Circulante/genética , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/genética , Medicina de Precisión , Mutación , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/genética , Biomarcadores de Tumor/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos
19.
ACS Appl Mater Interfaces ; 16(1): 943-956, 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38146938

RESUMEN

All-solid-state batteries (ASSBs) have attracted much attention in the fields of energy storage, electric vehicles, and portable electronic devices due to their safety and high energy density. Ni-rich layered ternary materials (LiNi1-y-zCoyMnzO2, 1 - y - z ≥ 0.7) are considered to be among the most promising candidates for cathode materials in ASSBs due to their unique advantages. Nevertheless, the interfacial chemical reaction between the ternary cathode (NCM) and solid-state electrolytes (SSEs) has become the main issue to limit the long-cycle stability of the cathode. Relative studies have shown that when NCM materials are in direct contact with sulfide-based SSEs, byproducts generated by the interfacial chemical reaction accumulate at the interface, resulting in increasing interfacial impedance. However, up to now, the formation mechanism of the NCM/SSE interfacial chemical reaction, as well as its properties and evolution process, still lacks detailed characterization. In this paper, batteries at different stages during the long-cycling process are characterized to reveal the dynamic evolution process of the chemical reaction from the cathode-electrolyte interface to the interior of the particle and to determine the chemical reaction effect on the irreversible degradation of the battery capacity. On this basis, a surface coating of LiNbO3 is adopted to establish a passivation protection layer at the cathode-electrolyte interface. The coated battery has been subjected to 2000 charge/discharge cycles at a rate of 1 C and achieved a capacity retention rate of up to 82%.

20.
Ecotoxicol Environ Saf ; 267: 115651, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37913581

RESUMEN

While existing research has illuminated the environmental dangers and neurotoxic effects of MC-LR exposure, the molecular underpinnings of brain damage from environmentally-relevant MC-LR exposure remain elusive. Employing a comprehensive approach involving RNA sequencing, histopathological examination, and biochemical analyses, we discovered genes differentially expressed and enriched in the ferroptosis pathway. This finding was associated with mitochondrial structural impairment and downregulation of Gpx4 and Slc7a11 in mice brains subjected to low-dose MC-LR over 180 days. Mirroring these findings, we noted reduced cell viability and GSH/GSSH ratio, along with an increased ROS level, in HT-22, BV-2, and bEnd.3 cells following MC-LR exposure. Intriguingly, MC-LR also amplified phospho-Erk levels in both in vivo and in vitro settings, and the effects were mitigated by treatment with PD98059, an Erk inhibitor. Taken together, our findings implicate the activation of the Erk/MAPK signaling pathway in MC-LR-induced ferroptosis, shedding valuable light on the neurotoxic mechanisms of MC-LR. These insights could guide future strategies to prevent MC-induced neurodegenerative diseases.


Asunto(s)
Células Endoteliales , Ferroptosis , Ratones , Animales , Encéfalo , Transducción de Señal
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