RESUMO
Nickel-aluminium layered double hydroxides (NiAl-LDHs) have emerged as promising electrode materials for supercapacitors (SCs) due to their inherently high specific surface area and theoretical specific capacitance, which are primarily attributed to the rapid pseudocapacitive response at the surface. However, NiAl-LDHs typically form agglomerated nanosheets, leading to a significant reduction in specific surface area, which is crucial for enhancing the number of active sites and improving the capacitive properties of the materials. To overcome this limitation, 2D nanostructures were assembled into 3D architectures by synthesizing NiAl-LDHs with distinct morphologies in a one-step hydrothermal process using an alkaline agent (NH4F). This approach resulted in the formation of 3D NiAl-LDH/HN4F structures, which exhibit a larger contact area and a greater number of redox-active sites. Consequently, the 3D NiAl-LDH/HN4F electrodes demonstrated a significantly higher specific surface area, leading to remarkable improvements in specific capacitance (1219 ± 30F g-1) and energy density (61 ± 1 Wh kg-1) compared to their 2D counterparts. This structural enhancement increases both the surface area and active site density while providing a new framework for designing high-performance LDH-based electrodes.
RESUMO
Nickel-iron layered double hydroxide (NiFe-LDH) is hindered in its further development in water splitting due to its slow kinetics of oxygen evolution reaction (OER) and hydrogen evolution reaction (HER). In this study, the synthesis of OER (FeO(OH)/NiFe-LDH) and HER (Fe7S8(NiS)/NiFe-LDH) catalysts endowed with inherent electric fields exhibited exceptional electrocatalytic properties. The presence of the built-in electric field modulated the redistribution of electrons within the catalyst, while the formation of a heterostructure preserved the intrinsic characteristics of the catalyst. Moreover, this electron redistribution optimized the catalyst's adsorption of reaction intermediates (O*, OH*, OOH*, and H*) during the catalytic process, thereby enhancing the performance of both OER and HER. The electrolytic cell, equipped with these catalysts, achieved the current density of 10 mA cm-2 at a remarkably low potential of 1.409 V under industrial temperature conditions and demonstrated an ultra-long-term stability of 200 h.
RESUMO
The ambient air quality has improved significantly under strict emission controls in Beijing, China over the last decade. Black carbon (BC), as a short-lived climate forcer in ambient aerosols, profoundly impacts the air quality and climate. Previous studies have demonstrated a decline in the mass concentration of BC. In this study, we characterized the chemical compositions and size distributions of BC-containing particles during the cold season of 2022 in Beijing using state-of-the-art instruments capable of exclusively measuring BC-containing particles. The optical properties of BC-containing particles were further calculated based on the Mie theory. Moreover, we compared the properties of BC-containing particles in 2022 with the results of previous studies. The results showed that the diameters of BC cores became larger while the coating thickness of BC-containing particles became thinner in 2022. For the coating materials, the mass fraction of nitrate increased obviously, and even replaced organic matter as the dominant component during the peak of the pollution period. Variations in chemical compositions and size distributions resulted in lower mass absorption cross-sections (MAC) of BC-containing particles from 10.5 ± 1.1 m2/g in 2016 to 7.3 ± 0.8 m2/g in 2022, reduced by 30.5%. Our results demonstrate the synergistic benefits of air pollution control in improving air quality and mitigating climate change. Therefore, the MAC of BC adopted in climate models should vary with the changing air pollution levels. This study emphasizes that it is imperative to conduct long-term observations of BC-containing particles to better estimate BC's climate effects.
Assuntos
Poluentes Atmosféricos , Monitoramento Ambiental , Material Particulado , Estações do Ano , Fuligem , Pequim , Fuligem/análise , Monitoramento Ambiental/métodos , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/química , Material Particulado/análise , Poluição do Ar/estatística & dados numéricos , Poluição do Ar/análise , Aerossóis/análise , Tamanho da PartículaRESUMO
In this phase II study, 47 patients with locally advanced, resectable esophageal squamous cell carcinoma (ESCC) received three cycles of pembrolizumab plus chemotherapy, followed by Da Vinci robot-assisted surgery. The primary endpoints were safety and major pathological response (MPR). Key secondary endpoints included complete pathological response (pCR) and survival. No grade ≥3 adverse events or surgical delays occurred during neoadjuvant therapy. Among 46 patients studied for efficacy, the MPR and pCR rates were 72% and 41%, respectively. After a median follow-up of 27.2 months, the 2-year overall survival (OS) and disease-free survival (DFS) rates were 91% and 89%, respectively. Expansion of TRGC2+ NKT cells in peripheral blood correlated with neoadjuvant treatment effectiveness, which was validated by in vitro organoid experiments and external cancer datasets, and its functional classification and mechanism of action were further explored. These findings show preoperative pembrolizumab plus chemotherapy is a promising therapeutic strategy for resectable ESCC.
Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Terapia Neoadjuvante , Humanos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Terapia Neoadjuvante/métodos , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Feminino , Pessoa de Meia-Idade , Masculino , Idoso , Estudos Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Adulto , Intervalo Livre de DoençaRESUMO
Background: Repetitive transcranial magnetic stimulation (rTMS) showed potentially beneficial effects for the treatment of post-traumatic stress disorder (PTSD). Low-frequency (LF) rTMS decreases neuronal excitability and may have better safety compared to high-frequency (HF) rTMS. However, there lacks meta-analysis specifically focusing on LF rTMS. Objectives: To specifically explore the efficacy and safety of LF rTMS for treating PTSD. Methods: Databases including PubMed, EMBASE, MEDLINE, and Web of Science were systematically searched from inception to October 17, 2023. Both randomized controlled trials (RCTs) and open trials of LF rTMS on PTSD were included, and we additionally included RCTs comparing HF rTMS and sham treatment on PTSD. First, we qualitatively summarized parameters of LF rTMS treatment; then, we extracted data from the LF rTMS treatment subgroups of these studies to examine its effect size and potential influencing factors; third, we compared the effect sizes among LF rTMS, HF rTMS and sham treatment through network meta-analysis of RCTs. Results: In all, 15 studies with a sample size of 542 participants were included. The overall effect size for LF rTMS as a treatment for PTSD was found as Hedges' g = 1.02 (95% CI (0.56, 1.47)). Meta-regression analysis did not reveal any influencing factors. Network meta-analysis showed that compared to sham treatment, only HF rTMS on the right dorsolateral prefrontal cortex (DLPFC) demonstrated a significant advantage in ameliorating PTSD symptoms, while LF rTMS on the right DLPFC showed a trend toward advantage, but the difference was not significant. Conclusion: The current literature shows LF rTMS has effect in treating PTSD caused by various traumatic events. However, present limited number of RCT studies only showed LF rTMS to have a trend of advantage compared to sham treatment in treating PTSD caused by external traumatic events. In the future, more RCTs are needed to be made to confirm the efficacy of LF rTMS. Additionally, studies are required to elucidate the underlying mechanism in order to further improve its efficacy in different traumatic populations. PROSPERO registration number: CRD42023470169.
RESUMO
Endoplasmic reticulum stress-induced cell apoptosis is a pivotal mechanism underlying the progression of cardiac hypertrophy. NLRX1, a member of the NOD-like receptor family, modulates various cellular processes, including STING, NF-κB, MAPK pathways, reactive oxygen species production, essential metabolic pathways, autophagy and cell death. Emerging evidence suggests that NLRX1 may offer protection against diverse cardiac diseases. However, the impacts and mechanisms of NLRX1 on endoplasmic reticulum stress in cardiac hypertrophy remains largely unexplored. In our study, we observed that the NLRX1 and phosphorylated STING (p-STING) were highly expressed in both hypertrophic mouse heart and cellular model of cardiac hypertrophy. Whereas over-expression of NLRX1 mitigated the expression levels of p-STING, as well as the endoplasmic reticulum stress markers, including transcription activating factor 4 (ATF4), C/EBP homologous protein (CHOP) and the ratios of phosphorylated PERK to PERK, phosphorylated IRE1 to IRE1 and phosphorylated eIF2α to eIF2α in an Angiotensin II (Ang II)-induced cellular model of cardiac hypertrophy. Importantly, the protective effects of NLRX1 were attenuated upon pretreatment with the STING agonist, DMXAA. Our findings provide the evidence that NLRX1 attenuates the PERK-eIF2α-ATF4-CHOP axis of endoplasmic reticulum stress response via inhibition of p-STING in Ang II-treated cardiomyocytes, thereby ameliorating the development of cardiac hypertrophy.
Assuntos
Cardiomegalia , Estresse do Retículo Endoplasmático , Proteínas de Membrana , Animais , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Cardiomegalia/genética , Camundongos , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Masculino , eIF-2 Quinase/metabolismo , eIF-2 Quinase/genética , Fator 4 Ativador da Transcrição/metabolismo , Fator 4 Ativador da Transcrição/genética , Fator de Transcrição CHOP/metabolismo , Fator de Transcrição CHOP/genética , Fosforilação , Camundongos Endogâmicos C57BL , Angiotensina II/farmacologia , Apoptose , Transdução de Sinais , Proteínas MitocondriaisRESUMO
BACKGROUND: Studies suggests a correlation between physical activity and mental health, particularly in children and adolescents. However, the specific mechanisms underlying this relationship is not fully understood. This study was designed to investigate the potential mediating role of emotion regulation and the moderating influence of gender through a moderated mediation model. METHODS: A sample size of 4763 students (mean age = 11.12 ± 1.48 years, 52.8 % females) from seven schools in Shenzhen, China, was recruited during the period of October to November 2023. The participants were administered self-reported questionnaires assessing physical activity, mental health, and emotion regulation. The moderated mediation model was analyzed. Data analysis was conducted using SPSS 25.0. RESULTS: The results indicate a negative correlation between physical activity and mental health problems (all p < 0.001). This association was partially mediated by both cognitive reappraisal and expressive suppression (all p < 0.001). Additionally, gender significant moderated the path between physical activity and emotion regulation, specifically cognitive reappraisal (p < 0.001) and expressive suppression (p < 0.01). LIMITATIONS: As a result of the cross-sectional design, no causal relationship could be established, and measurement bias should be noted. CONCLUSION: Physical activity is found to have a positive effect on the mental health problem of children and adolescents with emotion regulation serve as a partial mediator in the relationship. Additionally, in the mediation model, gender influences the first half of the path.
RESUMO
BACKGROUND: The integration of Virtual Reality (VR) with Case-Based Learning (CBL) has the potential to revolutionise undergraduate medical education, particularly in complex subjects such as the anatomy and rehabilitation of the shoulder joint. This study aimed to explore the effectiveness of this innovative approach in enhancing learning outcomes and knowledge retention. METHODS: This study employed a parallel-group, assessor-blinded randomised controlled trial (RCT) design. A comprehensive five-week educational programme was developed, combining traditional lecture-based learning with VR-enhanced CBL. The study involved 82 undergraduate students from China Medical University, who were divided into groups receiving different combinations of VR and CBL. Student performance was evaluated through tests and questionnaires. RESULTS: In the anatomy-related courses, the integration of VR technology with CBL yielded significantly higher results (87.71 ± 5.60) compared to traditional methods (82.59 ± 6.64), with a statistically significant difference (P < 0.05). This provides compelling evidence of VR's potential to enhance student engagement and knowledge retention. In the context of physiotherapy-related courses, however, while the test scores of the VR-combined CBL group (81.85 ± 5.99) were marginally higher than those of the traditional CBL group (79.02 ± 7.57), this difference was not statistically significant (P > 0.05). CONCLUSION: The present study provides preliminary evidence for the benefits of incorporating VR into medical education, particularly in anatomy. While the results are promising, further research is needed to explore the optimal integration of VR and CBL in rehabilitation studies and to assess their long-term impact on student learning and clinical performance. TRIAL REGISTRATION: The study was registered with Chinese Clinical Trials Registry (Registration Number: ChiCTR2400089295) on 05/09/2024.
Assuntos
Educação de Graduação em Medicina , Articulação do Ombro , Realidade Virtual , Humanos , Educação de Graduação em Medicina/métodos , Masculino , Feminino , Estudantes de Medicina , Adulto Jovem , Aprendizagem Baseada em Problemas/métodos , China , Avaliação Educacional , Anatomia/educação , CurrículoRESUMO
The presence of pathogens is one of the leading causes of stream water quality impairment in the US. Escherichia coli (E. coli) is a fecal pathogen indicator and also signals the presence of more pathogenic microbes. Although it is reported that Black, Indigenous, and communities of color suffer more from E. coli contamination, there is a lack of investigation of the potential inequality of E. coli contamination in recreational waterbodies, particularly regarding whether this inequality persists over the long term. Using E. coli monitoring data from 1,424 stations from 2001 to 2021 in Texas, we tested the research hypotheses of racial and economic inequalities in E. coli levels and trends with quantile regression and logistic regression approaches. We found that economic disparities had a more significant relationship with E. coli contamination in Texas recreational waterbodies than racial disparities after controlling for building age, land covers, imperviousness, and precipitation. The economic disparities in E. coli contamination were more prevalent after 2010 and in extreme E. coli levels. In addition, implementing watershed protection plans could mitigate the economic disparities associated with the rising trend of E. coli levels between 2001 and 2021. Findings from this research underscore clean surface water deprivation from underserved communities and call for inclusive watershed management strategies to address the water quality injustice.
RESUMO
While previous studies have identified a relationship between dietary intake and the risk of non-alcoholic fatty liver disease (NAFLD), the influence of overall nutritional status on NAFLD development has not been thoroughly investigated. This study sought to explore the association between different nutritional status indicators and NAFLD among the older adults. Nutritional status was evaluated using controlling nutritional status (CONUT), prognostic nutritional index (PNI) and nutritional risk index (GNRI), while NAFLD was identified based on a controlled attenuation parameter ≥ 285 dB/m, measured using transient elastography. The analysis included multivariate regression, receiver operating characteristic analysis, eXtreme Gradient Boosting and subgroup analysis to investigate the relationships between nutritional status indices and NAFLD. The study enrolled 1409 participants for the main analysis, with an NAFLD prevalence of 44·7 %. After accounting for potential confounders, a positive association between PNI and NAFLD was observed. Participants in the third and fourth quartiles of PNI showed increased odds of NAFLD compared with the lowest quartile (Q3: OR = 1·45, 95 % CI (1·03, 2·05); Q4: OR = 2·27, 95 % CI (1·59, 3·24)). Similarly, higher GNRI quartiles were significantly associated with greater odds of NAFLD (Q4 v. Q1: aOR = 1·84; 95 % CI (1·28, 2·65)). Conversely, higher CONUT values were linked to a reduced prevalence of NAFLD (OR = 0·65, 95 % CI (0·48, 0·87)). This study highlights that suboptimal nutritional status, indicating overnutrition as evaluated by PNI, GNRI and CONUT, is positively linked with the risk of NAFLD in individuals aged 50 years and above.
RESUMO
BACKGROUND: Sarcopenic obesity (SO) and osteoarthritis (OA) are highly prevalent musculoskeletal conditions that significantly impair health-related quality of life. AIM: This study investigated the association between SO and OA, and explored the potential mediating role of insulin resistance in this relationship. We utilized data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. METHODS: This cross-sectional analysis employs NHANES data collected from 1999 to 2018, including participants aged 18 years and older. SO was assessed using dual-energy X-ray absorptiometry (DXA) measurements. Insulin resistance was estimated using the triglyceride-glucose (TyG) index. OA status was based on self-reported physician diagnosis. Statistical analyses included weighted logistic regression, restricted cubic spline (RCS) interaction analysis, mediation analysis using structural equation modeling (SEM), and receiver operating characteristic (ROC) curve analysis. Subgroup analyses were conducted based on age, sex, and diabetes status. RESULTS: The sarcopenic obese group demonstrated the highest prevalence of OA (23.4 %), hypertension (47.8 %), and diabetes (12.0 %). Additionally, they exhibited elevated levels of triglycerides, cholesterol, glucose, blood urea nitrogen (BUN), creatinine, and uric acid. Logistic regression revealed significant positive associations between sarcopenic obesity, the TyG index, and OA risk. RCS analysis identified significant non-linear relationships and interactions of the TyG index with age, sex, and diabetes status on OA risk. Mediation analysis indicated that the TyG index mediated approximately 4.9 % of the effect of sarcopenic obesity on OA risk. ROC curve analysis demonstrated moderate diagnostic accuracy for the TyG index (AUC = 0.65), which improved when incorporated into the multivariate model (AUC = 0.78). Subgroup analyses confirmed significant associations between the TyG index and sarcopenic obesity with OA risk across different age, sex, and diabetes status categories. CONCLUSION: Our findings suggest a significant correlation between insulin resistance, as measured by the TyG index, and elevated OA risk in individuals with sarcopenic obesity. Targeting insulin resistance through future research may be a promising avenue to lower OA risk in this population.
Assuntos
Resistência à Insulina , Inquéritos Nutricionais , Obesidade , Osteoartrite , Sarcopenia , Humanos , Masculino , Feminino , Sarcopenia/epidemiologia , Sarcopenia/sangue , Sarcopenia/diagnóstico , Resistência à Insulina/fisiologia , Obesidade/complicações , Obesidade/sangue , Obesidade/epidemiologia , Osteoartrite/sangue , Osteoartrite/epidemiologia , Pessoa de Meia-Idade , Estudos Transversais , Idoso , Adulto , Absorciometria de Fóton , Prevalência , Glicemia/metabolismo , Modelos Logísticos , Triglicerídeos/sangueRESUMO
This study aimed to investigate the clinical outcomes of local muscle or myocutaneous flap transfer for emergent repair of Gustilo IIIB open tibiofibular fractures. This retrospective case series study included patients with Gustilo IIIB open tibiofibular fractures treated by local muscle or myocutaneous flap transfer in Weifang People's Hospital between May 2016 and April 2021. Fifteenpatients (11 males aged 19-72 years) were included. The follow-up ranged from 8 to 24 months. The ranges of bone healing time and wound healing time were 6-17 months and 1-3 weeks, respectively. The length of hospital stay was 26 days (11-50 days). All patients reported acceptable functional recovery and satisfactory leg appearance, with Johner-Wruhs scores of excellent, good, and fair in 10, four, and one patients, respectively. The excellent-good rate was 93.3%. The complications included one case of infection and one case of nonunion. In conclusion, local muscle or myocutaneous flap transfer for emergent repair of Gustilo IIIB open tibiofibular fractures may be useful in providing adequate soft tissue coverage and fracture healing with low complication and infection rates.
Assuntos
Fraturas Expostas , Retalho Miocutâneo , Humanos , Masculino , Pessoa de Meia-Idade , Adulto , Feminino , Idoso , Retalho Miocutâneo/transplante , Estudos Retrospectivos , Fraturas Expostas/cirurgia , Adulto Jovem , Fraturas da Tíbia/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Resultado do Tratamento , Fíbula/transplante , Retalhos Cirúrgicos , Cicatrização , Fraturas do Tornozelo/cirurgia , Músculo Esquelético/transplanteRESUMO
To explore the effect of scapula motion control training on the rehabilitation effect of patients with scapular fracture. According to the random number table method, 61 patients were evenly divided into observation group 30 cases and control group 31 cases. The control group received routine postoperative functional exercise, and the observation group received functional exercise by adding scapula motion control training to the routine postoperative functional exercise. The pain, daily activity, range of shoulder movement, strength test, and total score were compared between the 2 groups of patients at 4 and 12 weeks after surgery. After 4 and 12 weeks of treatment, compared with the control group, the daily activities, range of shoulder movements, and total scores of the observation group increased, and there were no significant differences in pain and strength tests. After 12 weeks of treatment, compared with the control group, the daily activity, range of shoulder movements, and total score of the observation group were higher than those of the control group. Scapular motion control training can effectively improve the treatment of patients with scapular fractures and has clinical application value.
Assuntos
Fraturas Ósseas , Amplitude de Movimento Articular , Escápula , Humanos , Escápula/lesões , Masculino , Feminino , Fraturas Ósseas/reabilitação , Fraturas Ósseas/terapia , Adulto , Pessoa de Meia-Idade , Terapia por Exercício/métodos , Resultado do TratamentoRESUMO
Accurate identification of animals and the verification of their parentage can be used to pedigree populations and support selective breeding. The International Society for Animal Genetics recommended 16 cattle STRs for individual identification and parentage testing in cattle, but no multiplex STR typing system contains these 16 STRs. Here, we develop an efficient 17-plex multiplex typing system for cattle that contains the 16 ISAG recommend STRs and a sex-determining marker. Compared to the Bovine Parenting Typing Kit (containing 11 of the 16 ISAG recommend STRs), our new typing system not only increases the number of molecular markers, but also simplifies the PCR operation and shortens the time for the typing procedure (from 4.5 h to 1 h 37 min). Profile can be generated from a single PCR reaction using as little as 1 ng of DNA. The combined probabilities of paternity exclusion CPEduo and CPEtrio were 0.999804697 and 0.999999260, respectively. These results indicate that our 17-plex typing system is a fast, sensitive and species-specific method for the identification of individuals and their parentage for cattle. The application of this system will improve the efficiency of the identification of cattle individuals and their paternity, supporting population genetic research and the selective breeding of cattle.
Assuntos
Repetições de Microssatélites , Animais , Bovinos/genética , Repetições de Microssatélites/genética , Linhagem , Feminino , Masculino , Reação em Cadeia da Polimerase Multiplex/métodosRESUMO
OBJECTIVE: To report a new case of gastroblastoma and conduct an exhaustive review of the clinical, morphological, immunohistochemical, molecular features, diagnosis, treatment, and prognosis, to enhance understanding of this condition. METHODS: We retrospectively analyzed the case of a 50-year-old woman diagnosed with gastroblastoma and conducted a review and summary of relevant literature. RESULTS: To date, 27 cases have been reported, including the present case. The mean patient age at the time of presentation was 35.0 years (range, 5-74 years), and the disease showed no sex predilection. The most common location was the gastric antrum, and the average lesions size was 5.7 cm (range, 1.3-15 cm). Most patients underwent gastrectomy(n = 23), while several underwent ESD(n = 2) or EFTR(n = 1). Fusion genes were identified, including MALAT1-GLI1(n = 8), EWSR1-CTBP1(n = 1), PTCH1:GLI2(n = 1), and ACTB-GLI1(n = 1)Four patients had metastasis and one of them dead of disease. Immunohistochemical (IHC) analysis revealed that pancytokeratin was always positive in epithelioid components, while vimentin and CD10 were always positive in mesenchymal components. CD56 were often positive in both two components. CONCLUSION: A comprehensive evaluation of clinical and pathological features is crucial for accurate diagnosis. Partial gastrectomy and EFTR could be an appropriate treatment. The risk factors that affect the prognosis need more cases to be clearly defined. We present this exhaustive literature review to increase awareness of gastroblastoma, better characterize the disease, and provide a reference point for gastroblastoma research in the future.
Assuntos
Neoplasias Gástricas , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/genética , Prognóstico , Gastrectomia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Estudos Retrospectivos , AdultoRESUMO
Climate-sensitive northern cryosphere inland waters emit greenhouse gases (GHGs) into the atmosphere, yet their total emissions remain poorly constrained. We present a data-driven synthesis of GHG emissions from northern cryosphere inland waters considering water body types, cryosphere zones, and seasonality. We find that annual GHG emissions are dominated by carbon dioxide ([Formula: see text] teragrams of CO2; [Formula: see text]) and methane ([Formula: see text] teragrams of CH4), while the nitrous oxide emission ([Formula: see text] gigagrams of N2O) is minor. The annual CO2-equivalent (CO2e) GHG emissions from northern cryosphere inland waters total [Formula: see text] or [Formula: see text] petagrams of CO2e using the 100- or 20-year global warming potentials, respectively. Rivers emit 64% more CO2e GHGs than lakes, despite having only one-fifth of their surface area. The continuous permafrost zone contributed half of the inland water GHG emissions. Annual CO2e emissions from northern cryosphere inland waters exceed the region's terrestrial net ecosystem exchange, highlighting the important role of inland waters in the cryospheric land-aquatic continuum under a warming climate.
RESUMO
Post-traumatic tendon adhesions significantly affect patient prognosis and quality of life, primarily stemming from the absence of effective preventive and curative measures in clinical practice. Current treatment modalities, including surgical excision and non-steroidal anti-inflammatory drugs, frequently exhibit limited efficacy or result in severe side effects. Consequently, the use of anti-adhesive barriers for drug delivery and implantation at the injury site to address peritendinous adhesion (PA) has attracted considerable attention. Electrospun nanofiber membranes (ENMs) have been extensively employed as drug-delivery platforms. In this study, we fabricated a polylactic acid (PLA)-dipyridamole (DP)-graft copolymer ENM called PLC-DP. This membrane exhibits enzyme-sensitive features, allowing more controlled and sustained drug release compared with conventional drug-loaded ENMs. In experiments, PLC-DP implantation reduced tissue adhesion by 47 % relative to the control group while not adversely affecting tendon healing. Mechanistically, PLC-DP effectively activates the FXYD domain containing ion-transport regulator 2 (FXYD2) protein, thereby downregulating the fibroblast-transforming growth factor beta (TGF-ß)/Smad3 signaling pathway. PLC-DP leverages the anti-adhesive properties of DP and the enzyme-sensitive characteristics of graft copolymers, providing a promising approach for the future clinical treatment and prevention of PA. STATEMENT OF SIGNIFICANCE: Peritendinous adhesions (PA) are a common and disabling condition that seriously affects the prognosis and quality of life of post-trauma patients. Current treatments often have limited efficacy or severe side effects, leaving a serious gap in clinical practice. We developed a significant biomaterial, poly(lactic acid)-dipyridamole graft copolymer electrospun nanofibrous membrane (PLC-DP), specifically for PA inhibition. In addition, this study uniquely combines dipyridamole, an anti-adhesive agent, and enzyme-sensitive copolymers in electrospun nanofibrous membrane. Unlike conventional drug-loaded electrospun nanofibrous membranes, PLC-DPs have enzyme-sensitive drug properties that allow for sustained drug release on demand. Our experiments showed that implantation of PLC-DP was effective in reducing tissue adhesions by 47 % without affecting tendon healing. We elucidated the mechanism behind this phenomenon, suggesting that PCD activates FXYD2 to inhibit TGF-ß-induced expression of Col III, which is a key factor in PA development.
Assuntos
Membranas Artificiais , Nanofibras , Poliésteres , Nanofibras/química , Aderências Teciduais/prevenção & controle , Aderências Teciduais/patologia , Aderências Teciduais/metabolismo , Aderências Teciduais/tratamento farmacológico , Animais , Poliésteres/química , Ratos Sprague-Dawley , Polímeros/química , Polímeros/farmacologia , MasculinoRESUMO
BACKGROUND: Conflicting results comparing bivalirudin versus heparin anticoagulation in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), in part due to the confounding effect of glycoprotein IIb/IIIa inhibitors (GPI). The aim of the study was to compare the safety and effectiveness of bivalirudin plus a post-PCI high-dose infusion vs heparin with or without bail-out GPI use. METHODS: We conducted a pre-specified subgroup analysis from the BRIGHT-4 trial that randomized 6016 STEMI patients who underwent primary PCI to receive either bivalirudin plus a post-PCI high-dose infusion for 2-4 h or heparin monotherapy. GPI use was only reserved as bail-out therapy for procedural thrombotic complications. The primary outcome was a composite of all-cause death or Bleeding Academic Research Consortium (BARC) types 3-5 bleeding at 30 days. RESULTS: A total of 5250 (87.4%) patients received treatment without GPI while 758 (12.6%) received bail-out GPI. Bail-out GPI use was associated with an increased risk of the primary outcome compared to non-GPI use (5.28% vs. 3.41%; adjusted hazard ratio (aHR), 1.62; 95% confidence interval (CI), 1.13-2.33; P = 0.009) and all-cause death (5.01% vs. 3.12%; aHR, 1.74; 95% CI, 1.20-2.52; P = 0.004) but not in the risk of BARC types 3-5 bleeding (0.53% vs. 0.48%; aHR, 0.90; 95% CI, 0.31-2.66; P = 0.85). Among patients without GPI use, bivalirudin was associated with lower rates of the primary outcome (2.63% vs. 4.21%; aHR, 0.55; 95% CI, 0.39-0.77; P = 0.0005), all-cause death (2.52% vs. 3.74%; aHR, 0.58; 95% CI, 0.41-0.83; P = 0.003), and BARC types 3-5 bleeding (0.15% vs. 0.81%; aHR, 0.19; 95% CI, 0.06-0.57; P = 0.003) compared with heparin. However, among patients requiring bail-out GPI, there were no significant differences observed in the rates of the primary outcome (5.76% vs. 4.87%; aHR, 0.77; 95% CI, 0.36-1.66; P = 0.50; Pinteraction = 0.07) or its individual components between bivalirudin and heparin groups. CONCLUSIONS: Bivalirudin plus a post-PCI high-dose infusion was associated with significantly reduced 30-day composite rate of all-cause death or BARC types 3-5 bleeding compared with heparin monotherapy in STEMI patients undergoing primary PCI without GPI use. However, these benefits might be less pronounced in patients requiring bail-out GPI due to thrombotic complications during primary PCI. TRIAL REGISTRATION: ClinicalTrials.gov NCT03822975.
Assuntos
Heparina , Hirudinas , Fragmentos de Peptídeos , Proteínas Recombinantes , Humanos , Hirudinas/administração & dosagem , Hirudinas/efeitos adversos , Heparina/uso terapêutico , Heparina/efeitos adversos , Heparina/administração & dosagem , Masculino , Proteínas Recombinantes/uso terapêutico , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Feminino , Fragmentos de Peptídeos/uso terapêutico , Fragmentos de Peptídeos/efeitos adversos , Fragmentos de Peptídeos/administração & dosagem , Pessoa de Meia-Idade , Idoso , Intervenção Coronária Percutânea/métodos , Resultado do Tratamento , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Anticoagulantes/uso terapêutico , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Antitrombinas/uso terapêutico , Antitrombinas/efeitos adversos , Antitrombinas/administração & dosagem , HemorragiaRESUMO
Cardiac arrhythmias remain a significant cause of mortality and morbidity, for novel antiarrhythmic therapies. This study states that the first report of sophoridine (SPN), a quinolizidine alkaloid derived from traditional Chinese herbs, shows promise as a potential candidate due to its anti-arrhythmic and antioxidant properties. The study found that cell viability in H9C2 rat cardiomyocytes remained stable even when treated with SPN at a higher dosage of 100 µg/ml. This phenomenon was accompanied by increases in mitochondria-derived reactive oxygen species (ROS) and calcium/calmodulin-dependent protein kinase II (CaMKII) signaling, at 50 and 100 µg/ml. Glucose fluctuations regulate ventricular arrhythmias caused by SPN by activating the ROS/CaMKII pathway. Experimental models using zebrafish provided additional evidence supporting the regulatory effects of SPN on heart rate. In addition, the administration of SPN resulted in substantial deregulation of crucial genes involved in heart development (nppa, nppb, tnnt2a) at the transcriptional level in zebrafish. These findings provide insight into the various pharmacological properties of SPN and this opens up new possibilities for anti-arrhythmic treatment strategies.
RESUMO
Enantioselective radical reactions mediated by TBADT have seldom been seen due to the inherent challenges. Herein, we disclose a new chiral hydrogen atom transfer (HAT) reagent that was generated easily from 8H-BINOL, potassium carbonate, and TBADT under irradiation. The new complex 8H-BINOL/DTs could be used as a chiral H donor. A series of azaarenes could be converted into the corresponding chiral compounds via radical addition followed by enantioselective HAT.