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1.
Diabetes Care ; 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39140891

RESUMO

OBJECTIVE: We aimed to assess the feasibility, clinical accuracy, and acceptance of a hospital-wide continuous glucose monitoring (CGM) policy with electronic health record (EHR)-integrated validation for insulin dosing. RESEARCH DESIGN AND METHODS: A hospital policy was developed and implemented at Stanford Health Care for using personal CGMs in lieu of fingerstick blood glucose (FSBG) monitoring. It included requirements specific to each CGM, accuracy monitoring protocols, and EHR integration. User experience surveys were conducted among a subset of patients and nurses. RESULTS: From November 2022 to August 2023, 135 patients used the CGM protocol in 185 inpatient encounters. This included 27% with type 1 diabetes and 24% with automated insulin delivery systems. The most-used CGMs were Dexcom G6 (44%) and FreeStyle Libre 2 (43%). Of 1,506 CGM validation attempts, 87.8% met the %20/20 criterion for CGM-based insulin dosing and 99.3% fell within Clarke zones A or B. User experience surveys were completed by 27 nurses and 46 patients. Most nurses found glucose management under the protocol effective (74%), easy to use (67%), and efficient (63%); 80% of nurses preferred inpatient CGM to FSBG. Most patients liked the CGM protocol (63%), reported positive CGM interactions with nursing staff (63%), and felt no significant interruptions to their diabetes management (63%). CONCLUSIONS: Implementation of a hospital-wide inpatient CGM policy supporting multiple CGM types with real-time accuracy monitoring and integration into the EHR is feasible. Initial feedback from nurses and patients was favorable, and further investigation toward broader use and sustainability is needed.

3.
Nat Commun ; 15(1): 6964, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39138195

RESUMO

Though RNAi and RNA-splicing machineries are involved in regulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication, their precise roles in coronavirus disease 2019 (COVID-19) pathogenesis remain unclear. Herein, we show that decreased RNAi component (Dicer and XPO5) and splicing factor (SRSF3 and hnRNPA3) expression correlate with increased COVID-19 severity. SARS-CoV-2 N protein induces the autophagic degradation of Dicer, XPO5, SRSF3, and hnRNPA3, inhibiting miRNA biogenesis and RNA splicing and triggering DNA damage, proteotoxic stress, and pneumonia. Dicer, XPO5, SRSF3, and hnRNPA3 knockdown increases, while their overexpression decreases, N protein-induced pneumonia's severity. Older mice show lower expression of Dicer, XPO5, SRSF3, and hnRNPA3 in their lung tissues and exhibit more severe N protein-induced pneumonia than younger mice. PJ34, a poly(ADP-ribose) polymerase inhibitor, or anastrozole, an aromatase inhibitor, ameliorates N protein- or SARS-CoV-2-induced pneumonia by restoring Dicer, XPO5, SRSF3, and hnRNPA3 expression. These findings will aid in developing improved treatments for SARS-CoV-2-associated pneumonia.


Assuntos
COVID-19 , Carioferinas , Ribonuclease III , SARS-CoV-2 , Fatores de Processamento de Serina-Arginina , Animais , Fatores de Processamento de Serina-Arginina/metabolismo , Fatores de Processamento de Serina-Arginina/genética , Humanos , Ribonuclease III/metabolismo , Ribonuclease III/genética , SARS-CoV-2/genética , COVID-19/metabolismo , COVID-19/virologia , COVID-19/genética , Camundongos , Carioferinas/metabolismo , Carioferinas/genética , RNA Helicases DEAD-box/metabolismo , RNA Helicases DEAD-box/genética , Regulação para Baixo , Pulmão/metabolismo , Pulmão/patologia , Pulmão/virologia , Masculino , Feminino , MicroRNAs/genética , MicroRNAs/metabolismo , Splicing de RNA , Autofagia/genética , Dano ao DNA , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B
4.
PLoS One ; 19(7): e0305343, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38968273

RESUMO

BACKGROUND: Salidroside (SAL), the main component of Rhodiola rosea extract, is a flavonoid with biological activities, such as antioxidative stress, anti-inflammatory, and hypolipidemic. In this study, the potential therapeutic targets and mechanisms of SAL against oxidative stress in retinal ganglion cells (RGCs) were investigated on the basis of in-vitro experiments, network pharmacology, and molecular docking techniques. METHODS: RGC oxidative stress models were constructed, and cell activity, reactive oxygen species (ROS), and apoptosis levels were examined for differences. The genes corresponding to rhodopsin, RGCs, and oxidative stress were screened from GeneCards, TCMSP database, and an analysis platform. The intersection of the three was taken, and a Venn diagram was drawn. Protein interactions, GO functional enrichment, and KEGG pathway enrichment data were analyzed by STRING database, Cytohubba plugin, and Metascape database. The key factors in the screening pathway were validated using qRT-PCR. Finally, molecular docking prediction was performed using MOE 2019 software, molecular dynamic simulations was performed using Gromacs 2018 software. RESULTS: In the RGC oxidative stress model in vitro, the cell activity was enhanced, ROS was reduced, and apoptosis was decreased after SAL treatment. A total of 16 potential targets of oxidative stress in SAL RGCs were obtained, and the top 10 core targets were screened by network topology analysis. GO analysis showed that SAL retinal oxidative stress treatment mainly involved cellular response to stress, transcriptional regulatory complexes, and DNA-binding transcription factor binding. KEGG analysis showed that most genes were mainly enriched in multiple cancer pathways and signaling pathways in diabetic complications, nonalcoholic fatty liver, and lipid and atherosclerosis. Validation by PCR, molecular docking and molecular dynamic simulations revealed that SAL may attenuate oxidative stress and reduce apoptosis in RGCs by regulating SIRT1, NRF2, and NOS3. CONCLUSION: This study initially revealed the antioxidant therapeutic effects and molecular mechanisms of SAL on RGCs, providing a theoretical basis for subsequent studies.


Assuntos
Apoptose , Glucosídeos , Simulação de Acoplamento Molecular , Farmacologia em Rede , Estresse Oxidativo , Fenóis , Espécies Reativas de Oxigênio , Células Ganglionares da Retina , Estresse Oxidativo/efeitos dos fármacos , Fenóis/farmacologia , Fenóis/química , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/metabolismo , Glucosídeos/farmacologia , Glucosídeos/química , Apoptose/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Animais , Ratos , Simulação de Dinâmica Molecular , Antioxidantes/farmacologia
5.
Mol Biol Rep ; 51(1): 795, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39001907

RESUMO

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a disease of unknown etiology characterized by a constant incidence rate. Unfortunately, effective pharmacological treatments for this condition are lacking and the identification of novel therapeutic approaches and underlying pathological mechanisms are required. This study investigated the potential of quercetin in alleviating pulmonary fibrosis by promoting autophagy and activation of the SIRT1/AMPK pathway. METHODS: Mouse models of IPF were divided into four treatment groups: control, bleomycin (BLM), quercetin (Q), and quercetin + EX-527 (Q + E) treatment. Pulmonary fibrosis was induced in the mouse models through intratracheal instillation of BLM. Various indexes were identified through histological staining, Western blotting analysis, enzyme-linked immunosorbent assay, immunohistochemistry, and transmission electron microscopy. RESULTS: Quercetin treatment ameliorated the pathology of BLM-induced pulmonary fibrosis of mice by reducing α-smooth muscle actin (α-SMA), collagen I (Col I), and collagen III (Col III) levels, and also improved the level of E-cadherin in lung tissue. Furthermore, Quercetin significantly enhanced LC3II/LC3I levels, decreased P62 expression, and increased the number of autophagosomes in lung tissue. These effects were accompanied by the activation of the SIRT1/AMPK pathway. Treatment with EX-527, an inhibitor for SIRT1, reversed all effects induced by quercetin. CONCLUSION: This study showed that quercetin could alleviate pulmonary fibrosis and improve epithelial-mesenchymal transition by acting on the SIRT1/AMPK signaling pathway, which may be achieved by regulating the level of autophagy.


Assuntos
Proteínas Quinases Ativadas por AMP , Autofagia , Bleomicina , Fibrose Pulmonar , Quercetina , Transdução de Sinais , Sirtuína 1 , Animais , Bleomicina/efeitos adversos , Quercetina/farmacologia , Sirtuína 1/metabolismo , Autofagia/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Camundongos , Proteínas Quinases Ativadas por AMP/metabolismo , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/patologia , Modelos Animais de Doenças , Masculino , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/metabolismo , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/patologia , Camundongos Endogâmicos C57BL
6.
Ann Intern Med ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38976882

RESUMO

BACKGROUND: Methadone maintenance treatment (MMT) is effective for managing opioid use disorder, but adverse effects mean that optimal therapy occurs with the lowest dose that controls opioid craving. OBJECTIVE: To assess the efficacy of acupuncture versus sham acupuncture on methadone dose reduction. DESIGN: Multicenter, 2-group, randomized, sham-controlled trial. (Chinese Clinical Trial Registry: ChiCTR2200058123). SETTING: 6 MMT clinics in China. PARTICIPANTS: Adults aged 65 years or younger with opioid use disorder who attended clinic daily and had been using MMT for at least 6 weeks. INTERVENTION: Acupuncture or sham acupuncture 3 times a week for 8 weeks. MEASUREMENTS: The 2 primary outcomes were the proportion of participants who achieved a reduction in methadone dose of 20% or more compared with baseline and opioid craving, which was measured by the change from baseline on a 100-mm visual analogue scale (VAS). RESULTS: Of 118 eligible participants, 60 were randomly assigned to acupuncture and 58 were randomly assigned to sham acupuncture (2 did not receive acupuncture). At week 8, more patients reduced their methadone dose 20% or more with acupuncture than with sham acupuncture (37 [62%] vs. 16 [29%]; risk difference, 32% [97.5% CI, 13% to 52%]; P < 0.001). In addition, acupuncture was more effective in decreasing opioid craving than sham acupuncture with a mean difference of -11.7 mm VAS (CI, -18.7 to -4.8 mm; P < 0.001). No serious adverse events occurred. There were no notable differences between study groups when participants were asked which type of acupuncture they received. LIMITATION: Fixed acupuncture protocol limited personalization and only 12 weeks of follow-up after stopping acupuncture. CONCLUSION: Eight weeks of acupuncture were superior to sham acupuncture in reducing methadone dose and decreasing opioid craving. PRIMARY FUNDING SOURCE: National Natural Science Foundation of China.

8.
Regen Biomater ; 11: rbae057, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38854680

RESUMO

The joint prosthesis plays a vital role in the outcome of total hip arthroplasty. The key factors that determine the performance of joint prostheses are the materials used and the structural design of the prosthesis. This study aimed to fabricate a porous tantalum (Ta) hip prosthesis using selective laser melting (SLM) technology. The feasibility of SLM Ta use in hip prosthesis was verified by studying its chemical composition, metallographic structure and mechanical properties. In vitro experiments proved that SLM Ta exhibited better biological activities in promoting osteogenesis and inhibiting inflammation than SLM Ti6Al4V. Then, the topological optimization design of the femoral stem of the SLM Ta hip prosthesis was carried out by finite element simulation, and the fatigue performance of the optimized prosthesis was tested to verify the biomechanical safety of the prosthesis. A porous Ta acetabulum cup was also designed and fabricated using SLM. Its mechanical properties were then studied. Finally, clinical trials were conducted to verify the clinical efficacy of the SLM Ta hip prosthesis. The porous structure could reduce the weight of the prosthesis and stress shielding and avoid bone resorption around the prosthesis. In addition, anti-infection drugs can also be loaded into the pores for infection treatment. The acetabular cup can be custom-designed based on the severity of bone loss on the acetabular side, and the integrated acetabular cup can repair the acetabular bone defect while achieving the function of the acetabular cup.

9.
J Environ Manage ; 363: 121444, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38852403

RESUMO

Waste activated sludge (WAS) and meat processing waste (MPW) were acted as co-substrates in anaerobic co-digestion (AcD), and biochemical methane potential (BMP) test was carried out to investigate the methane production performances. Microbial community structure and metabolic pathways analyses were conducted by 16S rRNA high-throughput sequencing and functional prediction analysis. BMP test results indicated that AcD of 70% WAS+30% MPW and 50% WAS+50% MPW (VS/VS) could significantly improve methane yield to 371.05 mL/g VS and 599.61 mL/g VS, respectively, compared with WAS acting as sole substrate (191.87 mL/g VS). The results of microbial community analysis showed that Syntrophomonas and Petrimonas became the dominant bacteria genera, and Methanomassiliicoccus and Methanobacterium became the dominant archaea genera after MPW addition. 16S functional prediction analysis results indicated that genes expression of key enzymes involved in syntrophic acetate oxidation (SAO), hydrogenotrophic and methylotrophic methanogenesis were up-regulated, and acetoclastic methanogenesis was inhibited after MPW addition. Based on these analyses, it could be inferred that SAO combined with hydrogenotrophic and methylotrophic methanogenesis was the dominant pathway for organics degradation and methane production during AcD. These findings provided systematic insights into the microbial community changes and metabolic pathways during AcD of WAS and MPW.


Assuntos
Metano , Esgotos , Esgotos/microbiologia , Anaerobiose , Metano/metabolismo , Redes e Vias Metabólicas , RNA Ribossômico 16S , Bactérias/metabolismo , Bactérias/genética , Carne , Archaea/metabolismo , Archaea/genética
10.
Diabetol Metab Syndr ; 16(1): 101, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38745237

RESUMO

BACKGROUND: The link between diabetes and dementia risk is not well understood. This study evaluates the factors linking diabetes to dementia onset, providing guidance for preventing dementia in diabetic patients. METHODS: This analysis utilized databases such as PubMed, Embase, Web of Science, and the Cochrane Library to review literature from January 31, 2012, to March 5, 2023. Articles were rigorously assessed using specific inclusion and exclusion criteria. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the studies. Data analysis was performed with STATA 15.0. RESULTS: The study analyzed 15 articles, covering 10,103,868 patients, with 8,821,516 diagnosed with diabetes. The meta-analysis reveals a substantial association between diabetes and an increased risk of dementia [RR: 1.59, 95%CI (1.40-1.80), P < 0.01, I²=96.4%]. A diabetes duration of less than five years is linked to a higher dementia risk [RR: 1.29, 95%CI (1.20-1.39), P < 0.01, I²=92.6%]. Additionally, hypoglycemia significantly raises dementia risk [RR: 1.56, 95%CI (1.13-2.16), P < 0.01, I²=51.5%]. Analyses of blood sugar control, glycated hemoglobin, and fasting blood sugar indicated no significant effects on the onset of dementia. CONCLUSION: Diabetes notably increases dementia risk, particularly where diabetes duration is under five years or hypoglycemia is present. REGISTRATION: The research protocol was registered with PROSPERO and assigned the registration number CRD42023394942.

11.
J Colloid Interface Sci ; 669: 825-834, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38749221

RESUMO

In this work, the nanocables of few-layered ReS2 nanosheets sandwiched between carbon nanotubes (CNTs) and nitrogen-doped amorphous carbon (NC) coating (i.e., CNT@ReS2@NC) are synthesized as high-performance anodes of both potassium-ion batteries (PIBs) and sodium-ion batteries (SIBs). The CNT@ReS2@NC nanocables with dual carbon modifications have the several advantages for efficient K+/Na+ storage. The few-layered ReS2 nanosheets with a wide interlayer spacing of 0.64 nm contribute to accelerated reaction kinetics for fast K+/Na+ intercalation/extraction. The carbon nanotube skeleton with a hollow interior can effectively relieve the volume change and serve as a robust conductive network to boost structural stability. The NC layer provides rich defects as active sites and suppresses the shuttle effect of polysulfides produced in discharge/charge processes. Consequently, the CNT@ReS2@NC nanocables possess outstanding electrochemical performance in both PIBs and SIBs owing to the synergistic effect from the different components. A long cycling lifespan of 3500 cycles with a maintained discharge capacity of 125 mAh/g is achieved for CNT@ReS2@NC at 1 A/g in PIBs. In SIBs, it can keep a high capacity of 202 mAh/g over 3000 cycles at 5 A/g. Moreover, the CNT@ReS2@NC||Na3V2(PO4)3 full cell can exhibit remarkable cycling performance, yielding a low capacity decay rate of 0.019 % per cycle over 1000 cycles at 2C.

12.
Cardiovasc Toxicol ; 24(7): 646-655, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38801481

RESUMO

This research is concentrated on investigating the role and mechanism of miR-652-3p in the protective effects of isoflurane (ISO) against myocardial ischemia-reperfusion (I/R) injury. H9c2 cells underwent pretreatment with varying concentrations of ISO, and subsequently, a hypoxia/reoxygenation (H/R) model was constructed. The levels of miR-652-3p, ISL LIM homeobox 1 (ISL1), and inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α) were evaluated through reverse transcription polymerase chain reaction (RT-qPCR). Enzyme-linked immunosorbent assay was employed to investigate concentrations of myocardial injury markers, such as creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI). Cell counting kit-8 was used to evaluate cell viability, while flow cytometry was utilized to measure apoptosis. Additionally, a dual luciferase reporter assay was conducted to validate the targeting relationship between ISL1 and miR-652-3p. Herein, we confirmed that the level of miR-652-3p was gradually increased with prolonged hypoxia; nevertheless, this increase was suppressed by ISO pretreatment (P < 0.05). Additionally, ISO pretreatment prevented the decrease in cell viability, increase in apoptosis, and overproduction of IL-6, TNF-α, CK-MB, and cTnI induced by H/R (P < 0.05). However, the inhibitory effects of ISO were counteracted by the increased levels of miR-652-3p (P < 0.05). ISL1 is a potential target of miR-652-3p. H/R induction suppressed ISL1 levels compared to the control, but ISO treatment increased its expression (P < 0.05). Overexpression of ISL1 inhibited the elimination of the protective effect of ISO on myocardial damage induced by the elevation of miR-652-3p (P < 0.05). The findings of this research confirm that miR-652-3p attenuated the protective effect of ISO on cardiomyocytes in myocardial ischemia by targeting ISL1.


Assuntos
Apoptose , Hipóxia Celular , Interleucina-6 , Isoflurano , Proteínas com Homeodomínio LIM , MicroRNAs , Traumatismo por Reperfusão Miocárdica , Miócitos Cardíacos , Fatores de Transcrição , MicroRNAs/metabolismo , MicroRNAs/genética , Isoflurano/farmacologia , Proteínas com Homeodomínio LIM/metabolismo , Proteínas com Homeodomínio LIM/genética , Animais , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/enzimologia , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/genética , Linhagem Celular , Apoptose/efeitos dos fármacos , Ratos , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Interleucina-6/metabolismo , Interleucina-6/genética , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Creatina Quinase Forma MB/metabolismo , Creatina Quinase Forma MB/sangue , Troponina I/metabolismo , Citoproteção
13.
Materials (Basel) ; 17(7)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38612086

RESUMO

The mechanical properties of metastable ß-titanium alloys are highly susceptible during the thermal mechanical processing (TMP). In this process, the recrystallization process plays an important role in determining the microstructure and texture evolution. The implementation of dynamic recrystallization (DRX), a process for achieving ß-grain refinement, is considered of great significance for the improvement of the properties of metastable ß-titanium alloys and their industrial production. Along these lines, in this work, an isothermal compression test of TB8 titanium alloy was carried out by using a Gleeble-3500 thermal simulator. As a result, the rheological stress behavior was analyzed, the thermal processing map was accurately established based on the stress-strain curve, and the optimal processing interval was determined. The DRX kinetic and the DRX grain size models were developed, on the basis of which a new DRX intrinsic model was established to improve the material parameters. Therefore, the actual situation in the working process could be better predicted. The microstructural evolution of TB8 titanium alloy during thermal deformation was comprehensively investigated using the electron backscatter diffraction (EBSD) technique. The obtained results demonstrate a close correlation between the diversity of DRX mechanisms in TB8 alloy and the distribution of dislocation density. Four microstructural textures during thermal deformation were identified, in which the cube texture of (001) <010> and the R-Gorss Nd texture of (110) <110> dominate. Due to the random orientation of the dynamically recrystallized grains, the strength of the R-Gorss Nd texture of (110) <110> increases with the increase in the volume fraction of DRX. On the contrary, it was verified that the dynamic recrystallization behavior has a significant weakening impact on the cube texture of (001) <010>.

14.
J Am Chem Soc ; 146(17): 11782-11791, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38639158

RESUMO

Metal halide perovskite materials inherently possess imperfections, particularly under nonequilibrium conditions, such as exposure to light or heat. To tackle this challenge, we introduced stearate ligand-capped nickel oxide (NiOx), a redox-sensitive metal oxide with variable valence, into perovskite intermediate films. The integration of NiOx improved the efficiency and stability of perovskite solar cells (PSCs) by offering multifunctional roles: (1) chemical passivation for ongoing defect repair, (2) energetic passivation to bolster defect tolerance, and (3) field-effect passivation to mitigate charge accumulation. Employing a synergistic approach that tailored these three passivation mechanisms led to a substantial increase in the devices' efficiencies. The target cell (0.12 cm2) and module (18 cm2) exhibited efficiencies of 24.0 and 22.9%, respectively. Notably, the encapsulated modules maintained almost 100 and 87% of the initial efficiencies after operating for 1100 h at the maximum power point (60 °C, 50% RH) and 2000 h of damp-heat testing (85 °C, 85% RH), respectively. Outdoor real-time tests further validated the commercial viability of the NiOx-assisted PSMs. The proposed passivation strategy provides a practical and uncomplicated approach for fabricating high-efficiency and stable photovoltaics.

15.
Sci Total Environ ; 929: 172643, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38649049

RESUMO

Particulate inorganic nitrogen aerosols (PIN) significantly influence air pollution and pose health risks worldwide. Despite extensive observations on ammonium (pNH4+) and nitrate (pNO3-) aerosols in various regions, their key sources and mechanisms in the Tibetan Plateau remain poorly understood. To bridge this gap, this study conducted a sampling campaign in Lhasa, the Tibetan Plateau's largest city, with a focus on analyzing the multiple isotopic signatures (δ15N, ∆17O). These isotopes were integrated into a Bayesian mixing model to quantify the source contributions and oxidation pathways for pNH4+ and pNO3-. Our results showed that traffic was the largest contributor to pNH4+ (31.8 %), followed by livestock (25.4 %), waste (21.8 %), and fertilizer (21.0 %), underscoring the impact of vehicular emissions on urban NH3 levels in Lhasa. For pNO3-, coal combustion emerged as the largest contributor (27.3 %), succeeded by biomass burning (26.3 %), traffic emission (25.3 %), and soil emission (21.1 %). In addition, the ∆17O-based model indicated a dominant role of NO2 + OH (52.9 %) in pNO3- production in Lhasa, which was similar to previous observations. However, it should be noted that the NO3 + volatile organic component (VOC) contributed up to 18.5 % to pNO3- production, which was four times higher than the Tibetan Plateau's background regions. Taken together, the multidimensional isotope analysis performed in this study elucidates the pronounced influence of anthropogenic activities on PIN in the atmospheric environment of Lhasa.

16.
Neurooncol Adv ; 6(1): vdae032, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38560348

RESUMO

Tumor-treating fields (TTFields) are currently a Category 1A treatment recommendation by the US National Comprehensive Cancer Center for patients with newly diagnosed glioblastoma. Although the mechanism of action of TTFields has been partly elucidated, tangible and standardized metrics are lacking to assess antitumor dose and effects of the treatment. This paper outlines and evaluates the current standards and methodologies in the estimation of the TTFields distribution and dose measurement in the brain and highlights the most important principles governing TTFields dosimetry. The focus is on clinical utility to facilitate a practical understanding of these principles and how they can be used to guide treatment. The current evidence for a correlation between TTFields dose, tumor growth, and clinical outcome will be presented and discussed. Furthermore, we will provide perspectives and updated insights into the planning and optimization of TTFields therapy for glioblastoma by reviewing how the dose and thermal effects of TTFields are affected by factors such as tumor location and morphology, peritumoral edema, electrode array position, treatment duration (compliance), array "edge effect," electrical duty cycle, and skull-remodeling surgery. Finally, perspectives are provided on how to optimize the efficacy of future TTFields therapy.

17.
Sci Total Environ ; 926: 171583, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38461977

RESUMO

Dual isotopes of nitrogen and oxygen of NO3- are crucial tools for quantifying the formation pathways and precursor NOx sources contributing to atmospheric nitrate. However, further research is needed to reduce the uncertainty associated with NOx proportional contributions. The acquisition of nitrogen isotopic composition from NOx emission sources lacks regulation, and its impact on the accuracy of contribution results remains unexplored. This study identifies key influencing factors of source isotopic composition through statistical methods, based on a detailed summary of δ15N-NOx values from various sources. NOx emission sources are classified considering these factors, and representative means, standard deviations, and 95 % confidence intervals are determined using the bootstrap method. During the sampling period in Tianjin in 2022, the proportional nitrate formation pathways varied between sites. For suburban and coastal sites, the ranking was [Formula: see text] (NO2 + OH radical) > [Formula: see text] (N2O5 + H2O) > [Formula: see text] (NO3 + DMS/HC), while the rural site exhibited similar fractional contributions from all three formation pathways. Fossil fuel NOx sources consistently contributed more than non-fossil NOx sources in each season among three sites. The uncertainties in proportional contributions varied among different sources, with coal combustion and biogenic soil emission showing lower uncertainties, suggesting more stable proportional contributions than other sources. The sensitivity analysis clearly identifies that the isotopic composition of 15N-enriched and 15N-reduced sources significantly influences source contribution results, emphasizing the importance of accurately characterizing the localized and time-efficient nitrogen isotopic composition of NOx emission sources. In conclusion, this research sheds light on the importance of addressing uncertainties in NOx proportional contributions and emphasizes the need for further exploration of nitrogen isotopic composition from NOx emission sources for accurate atmospheric nitrate studies.

18.
Clin Kidney J ; 17(3): sfae022, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38444751

RESUMO

Background: The prognostic significance of beta(ß)-blocker therapy in patients at end-stage renal disease, specifically those receiving peritoneal dialysis (PD) and presenting with heart failure, remains inadequately elucidated due to limited research conducted thus far. Methods: A retrospective analysis was performed on a cohort comprising 608 patients receiving PD between September 2007 and March 2019, with a subsequent follow-up period extending until December 2020. Cox regression and propensity score matching weighted analysis was used to model adjusted hazard ratios for ß-blocker use with heart failure-related mortality. Competing risk analysis and subgroup analysis were carried out to further elucidate the correlation. Results: ß-blockers were prescribed for 56.1% of the peritoneal dialysis patients. Heart failure occurred in 43.4% of the total population and 15.5% of deaths were due to heart failure. The prescription of ß-blockers was associated with a 43% lower adjusted hazard ratio (HR) for heart failure death within the cohort (95% confidence interval [CI] = 0.36-0.89; P = 0.013). Even after accounting for competing risk events, patients in the group using ß-blockers demonstrated a significantly lower cumulative risk of heart failure-related mortality compared to those not using ß-blockers (P = 0.007). This protective effect of ß-blockers was also observed in subgroup analyses. Conversely, ß-blocker use had no statistically significant associations with all-cause mortality. Conclusion: The use of ß-blockers was associated with a reduced risk of heart failure-related mortality in the PD population. Future randomized clinical trials are warranted to confirm the beneficial effect of ß-blockers in the context of PD.

19.
World J Gastrointest Oncol ; 16(2): 287-299, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38425393

RESUMO

Esophageal cancer (ESC) is a malignant tumor that originates from the mucosal epithelium of the esophagus and is part of the digestive tract. Although the exact pathogenesis of ESC has not been fully elucidated, excessive oxidative stress is an important characteristic that leads to the development of many cancers. Abnormal expression of several proteins and transcription factors contributes to oxidative stress in ESCs, which alters the growth and proliferation of ESCs and promotes their metastasis. Natural compounds, including alkaloids, terpenes, polyphenols, and xanthine compounds, can inhibit reactive oxygen species production in ESCs. These compounds reduce oxidative stress levels and subsequently inhibit the occurrence and progression of ESC through the regulation of targets and pathways such as the cytokine interleukins 6 and 10, superoxide dismutase, the NF-+ACY-kappa+ADs-B/MAPK pathway, and the mammalian Nrf2/ARE target pathway. Thus, targeting tumor oxidative stress has become a key focus in anti-ESC therapy. This review discusses the potential of Natural products (NPs) for treating ESCs and summarizes the application prospects of oxidative stress as a new target for ESC treatment. The findings of this review provide a reference for drug development targeting ESCs. Nonetheless, further high-quality studies will be necessary to determine the clinical efficacy of these various NPs.

20.
J Phys Chem A ; 128(12): 2366-2375, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38489755

RESUMO

Accurate spectroscopic data of carbon dioxide are widely used in many important applications, such as carbon monitoring missions. Here, we present comb-locked cavity ring-down saturation spectroscopy of the second most abundant isotopologue of CO2, 13C16O2. We determined the positions of 88 lines in three vibrational bands in the 1.6 µm region, 30011e/30012e/30013e-00001e, with an accuracy of a few kHz. Based on the analysis of combination differences, we obtained for the first time the ground-state rotational energies with kHz accuracy. We also provide a set of hybrid line positions for 150 13C16O2 transitions. The rotational energies (J < 50) in the 30013e vibrational state can be fitted by a set of rotational and centrifugal constants with deviations within a few kHz, indicating that the 30013e state is free of perturbations. These precise isotopic line positions will be utilized to improve the Hamiltonian model and quantitative remote sensing of carbon dioxide. Moreover, they will help to track changes in the carbon source and sink through isotopic analysis.

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