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1.
Comput Struct Biotechnol J ; 23: 3199-3210, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39263209

RESUMEN

Inferring the interactions between genes is essential for understanding the mechanisms underlying biological processes. Gene networks will change along with the change of environment and state. The accumulation of gene expression data from multiple states makes it possible to estimate the gene networks in various states based on computational methods. However, most existing gene network inference methods focus on estimating a gene network from a single state, ignoring the similarities between networks in different but related states. Moreover, in addition to individual edges, similarities and differences between different networks may also be driven by hub genes. But existing network inference methods rarely consider hub genes, which affects the accuracy of network estimation. In this paper, we propose a novel node-based joint Gaussian copula graphical (NJGCG) model to infer multiple gene networks from gene expression data containing heterogeneous samples jointly. Our model can handle various gene expression data with missing values. Furthermore, a tree-structured group lasso penalty is designed to identify the common and specific hub genes in different gene networks. Simulation studies show that our proposed method outperforms other compared methods in all cases. We also apply NJGCG to infer the gene networks for different stages of differentiation in mouse embryonic stem cells and different subtypes of breast cancer, and explore changes in gene networks across different stages of differentiation or different subtypes of breast cancer. The common and specific hub genes in the estimated gene networks are closely related to stem cell differentiation processes and heterogeneity within breast cancers.

2.
JBJS Rev ; 12(9)2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39226392

RESUMEN

¼ We aimed to determine the cost-effectiveness of different protocols of extended postoperative antibiotic prophylaxis (E-PAP) following adult spinal surgery.¼ Both stratified (randomized controlled trials only) and nonstratified (all studies) analyses demonstrated that E-PAP has no significant value in reducing the rate of surgical site infection (SSI), deep SSI, or superficial SSI.¼ Notably, the E-PAP protocols were associated with a significant increase in the length of hospital stay, resulting in an additional expenditure of $244.4 per episode for the E-PAP 72 hours protocol compared with PAP 24 hours and $309.8 per episode for the E-PAP >48 hours protocol compared with PAP <48 hours.¼ E-PAP does not demonstrate any significant reduction in the rate of SSIs following spine surgery. However, these extended protocols were significantly associated with an increase in the length of hospital stay and higher overall projected costs.


Asunto(s)
Profilaxis Antibiótica , Columna Vertebral , Infección de la Herida Quirúrgica , Adulto , Humanos , Antibacterianos/administración & dosificación , Antibacterianos/economía , Profilaxis Antibiótica/economía , Profilaxis Antibiótica/métodos , Tiempo de Internación/economía , Tiempo de Internación/estadística & datos numéricos , Columna Vertebral/cirugía , Infección de la Herida Quirúrgica/economía , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/prevención & control , Análisis de Costo-Efectividad
3.
Cureus ; 16(8): e67859, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39328684

RESUMEN

Background Skin adhesive tapes (SATs) are hypoallergenic adhesive tapes commonly used for wound closure in percutaneous vertebroplasty (PVP). Vertebral body stenting (VBS) is a metallic balloon-expandable stent used to treat vertebral body fractures. Its balloon and stent deployment involves a larger stab incision and pedicle bore tract than PVP, increasing the risk of bleeding and wound complications. This study evaluated the outcome and complications of VBS wound closure with SAT and the reasons for conversion to conventional suture closure (SC). Material and methods A retrospective series of patients who underwent VBS from May 2019 to March 2021 were identified from review of computerized medical records. Data were collected for wound closure method, reason for SC, number of operative levels, postoperative wound complications of contact dermatitis, tension blisters, tape dislodgement, surgical site infection, wound dehiscence, symptomatic hematoma and return to operating theater. The wounds were assessed for complete healing and cosmesis at outpatient follow-up visits. Results A total of 36 patients were identified. SAT closure was performed in 33 (91.6%) patients, while SC was performed in three (8.3%) patients. Unplanned conversion to SC was required in two (5.5%) patients due to continued intraoperative wound bleeding, while one (2.7%) patient had planned SC as part of a staged operation. Uneventful closures occurred in 32 (97.0%) of SAT closures. One (3%) SAT closure patient developed postoperative blood-soaked dressings and tape dislodgement, requiring reapplication of the SATs at the ward with uneventful recovery thereafter. No patient with SAT closure developed contact dermatitis, tension blisters, surgical site infection, wound dehiscence, symptomatic hematoma, or required return to theater. All SAT closure patients had complete wound healing at outpatient follow-up at six weeks. No SAT closure was found to be cosmetically unacceptable or required wound revision for any reason at up to one year postoperatively. Conclusion SATs are a safe and reliable means of wound closure for VBS. Conversion to SC due to continued intraoperative wound site bleeding is rarely required.

4.
Immunol Res ; 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39254909

RESUMEN

Multiple myeloma (MM) is a malignancy of plasma cells accompanied by immune dysfunction. This study aimed to provide a comprehensive and dynamic characterization of the peripheral immune environment in MM patients and find its diagnostic and prognostic values for therapy. The peripheral immune profiles of MM inpatients and healthy controls were assessed by flow cytometry. A longitudinal study of immune subsets was observed during cycles of chemotherapy. The diagnostic and prognostic models were established based on immune subsets by the absolute shrinkage and selection operator (LASSO) and multivariate regression. MM patients possessed an impeded immune landscape, including reduced activation of B cells, increased effective T cells and regulatory T cells (Tregs), augmented CD16 expression on monocytes and dendritic cell percentages, decreased CD56dimCD16+ natural killer cells (NKs), and amplified CD56bright and HLA-DR+ natural killer T cells (NKTs). Chemotherapy has different dynamic effects on specific cells, of which 2 cycles is the key turning point. NKT, dendritic cells, naïve Tc and Th cells, HLA-DR+ Tc cells, CD56dim NKTs, CD16++ monocytes, and CD25+ B cells could have the diagnostic value, and a prognostic model including neutrophils, naïve Tc cells, CD56brightCD16dim NKs, and CD16+ dendritic cells was established with acceptable accuracy. Our data showed dynamic and abnormal peripheral immune profiles in MM patients, which had prognostic values and could provide the basis for clinical therapy.

5.
Acta Pharmacol Sin ; 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39223367

RESUMEN

PANoptosis is an emerging form of regulated cell death (RCD) characterized by simultaneous activation of pyroptotic, apoptotic, and necroptotic signaling that not only participates in pathologies of inflammatory diseases but also has a critical role against pathogenic infections. Targeting PANoptosis represents a promising therapeutic strategy for related inflammatory diseases, but identification of inhibitors for PANoptosis remains an unmet demand. Baicalin () is an active flavonoid isolated from Scutellaria baicalensis Georgi (Huangqin), a traditional Chinese medicinal herb used for heat-clearing and detoxifying. Numerous studies suggest that baicalin possesses inhibitory activities on various forms of RCD including apoptosis/secondary necrosis, pyroptosis, and necroptosis, thereby mitigating inflammatory responses. In this study we investigated the effects of baicalin on PANoptosis in macrophage cellular models. Primary macrophages (BMDMs) or J774A.1 macrophage cells were treated with 5Z-7-oxozeaenol (OXO, an inhibitor for TAK1) in combination with TNF-α or LPS. We showed that OXO plus TNF-α or LPS induced robust lytic cell death, which was dose-dependently inhibited by baicalin (50-200 µM). We demonstrated that PANoptosis induction was accompanied by overt mitochondrial injury, mitochondrial DNA (mtDNA) release and Z-DNA formation. Z-DNA was formed from cytosolic oxidized mtDNA. Both oxidized mtDNA and mitochondrial Z-DNA puncta were co-localized with the PANoptosome (including ZBP1, RIPK3, ASC, and caspase-8), a platform for mediating PANoptosis. Intriguingly, baicalin not only prevented mitochondrial injury but also blocked mtDNA release, Z-DNA formation and PANoptosome assembly. Knockdown of ZBP1 markedly decreased PANoptotic cell death. In a mouse model of hemophagocytic lymphohistiocytosis (HLH), administration of baicalin (200 mg/kg, i.g., for 4 times) significantly mitigated lung and liver injury and reduced levels of serum TNF-α and IFN-γ, concomitant with decreased levels of PANoptosis hallmarks in these organs. Baicalin also abrogated the hallmarks of PANoptosis in liver-resident macrophages (Kupffer cells) in HLH mice. Collectively, our results demonstrate that baicalin inhibits PANoptosis in macrophages by blocking mitochondrial Z-DNA formation and ZBP1-PANoptosome assembly, thus conferring protection against inflammatory diseases. PANoptosis is a form of regulated cell death displaying simultaneous activation of pyroptotic, apoptotic, and necroptotic signaling. This study shows that induction of PANoptosis is linked to mitochondrial dysfunction and mitochondrial Z-DNA formation. Baicalin inhibits PANoptosis in macrophages in vitro via blocking mitochondrial dysfunction and the mitochondrial Z-DNA formation and thereby impeding the assembly of ZBP1-associated PANoptosome. In a mouse model of hemophagocytic lymphohistiocytosis (HLH), baicalin inhibits the activation of PANoptotic signaling in liver-resident macrophages (Kupffer cells) in vivo, thus mitigating systemic inflammation and multiple organ injury in mice.

6.
Chemosphere ; 364: 143095, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39146995

RESUMEN

The presence of organic compounds on the particulate matter (PM) or aerosols can arise from the condensation of gaseous organic compounds on the existing aerosols, or from organic precursors to form secondary organic aerosols (SOA) through photochemistry. The objective of this study is to characterize organic constituents on aerosols relevant to their emission sources and the key compounds revealing the evolution of aerosols with the use of a novel analytical technique. A time-of-flight mass spectrometry (TOFMS) coupled with comprehensive two-dimensional gas chromatography (GC×GC) was developed using a flow type of modulator instead of a thermal type as a prelude to field applications without the need for cryogen. The methodology of GC×GC-TOFMS is discussed in this study in detail. Since the coarse PM (PM10-2.5) may exhibit with a relatively high OC content compared to PM2.5, the GC×GC results have been obtained by analyzing PM10 samples collected in parallel with OC/EC analysis of PM2.5 samples at the Lulin Atmospheric Background Station (LABS, 23.47°N, 120.87°E, 2862 m ASL) as the high-mountain background site in East Asia. We found that the organic analytes were in a majority in the range of 12-30 carbon numbers falling in the category of semi-volatile organic compounds (SVOCs) with 43 compounds of alcohol, aldehyde, ketone, and ester varieties if excluding alkanes. Intriguingly, trace amounts of plasticizers and phosphorus flame retardants such as phthalates (PAEs) and triphenyl phosphate (TPP) were also found, likely originating from regions involved in open burning of household solid waste in Southeast Asia or e-waste recycling in southern China and along the long-range transport route. Compounds such as these are unique to the specific sources, demonstrating the wide spread of these hazardous compounds in the environment.


Asunto(s)
Aerosoles , Contaminantes Atmosféricos , Monitoreo del Ambiente , Compuestos Orgánicos , Material Particulado , Aerosoles/análisis , Contaminantes Atmosféricos/análisis , Asia Oriental , Atmósfera/química , Monitoreo del Ambiente/métodos , Cromatografía de Gases y Espectrometría de Masas , Compuestos Orgánicos/análisis , Material Particulado/análisis , Compuestos Orgánicos Volátiles/análisis
7.
Sci Total Environ ; 950: 175415, 2024 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-39128514

RESUMEN

The atrazine (ATR) is extensively used in dryland crops like corn and sorghum in black soil region of Northeast China, posing ecological risks due to toxic metabolites. Vermicompost are known for soil organic pollution remediation but their role in pesticide degradation in black soil remains understudied. The influence of vermicompost on the microbial degradation pathway of atrazine was assessed in this study. Although vermicompost didn't significantly boost atrazine removal, they notably aided in primary metabolite degradation, hydroxyatrazine (HYA), deisopropylatrazine (DIA), and deethylatrazine (DEA), reducing their content by 38.67 %. They also altered the soil microbial community structure, favoring atrazine-degrading bacteria like Proteobacteria, Firmicutes, and Actinobacteria. Five secondary degradation products were identified in vermicompost treatments. Atrazine degradation occurred via dechlorination, dealkylation, and deamination pathways mainly by Nocardioidacea, Streptomycetaceae, Bacillaceae, Sphingomonadaceae, Comamonadaceae and Nitrososphaeraceae. pH and available nitrogen (AN) influenced microbial community structure and atrazine degradation, correlating with vermicompost application rates. Future black soil remediation should optimize application rates based on atrazine content and soil properties.


Asunto(s)
Atrazina , Biodegradación Ambiental , Microbiología del Suelo , Contaminantes del Suelo , Suelo , Atrazina/metabolismo , Contaminantes del Suelo/metabolismo , China , Suelo/química , Herbicidas/metabolismo , Compostaje , Bacterias/metabolismo
8.
Asian J Surg ; 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39117541

RESUMEN

Lung cancer is a leading cause of cancer-related mortality worldwide, profoundly affecting patients' quality of life. Patient-reported outcomes (PROs) provide essential insights from the patients' perspective, a crucial aspect often overlooked by traditional clinical outcomes. This review synthesizes research on the role of PROs in lung cancer surgery to enhance patient care and outcomes. We conducted a comprehensive literature search across PubMed, Scopus, and Web of Science up to March 2024, using terms such as "lung cancer," "Patient Reported Outcome," "lobectomy," "segmentectomy," and "lung surgery." The criteria included original studies on lung cancer patients who underwent surgical treatment and reported on PROs. After screening and removing duplicates, reviews, non-English articles, and irrelevant studies, 36 research articles were selected, supported by an additional 53 publications, totaling 89 references. The findings highlight the utility of PROs in assessing post-surgical outcomes, informing clinical decisions, and facilitating patient-centered care. However, challenges in standardization, patient burden, and integration into clinical workflows remain, underscoring the need for further research and methodological refinement. PROs are indispensable for understanding the quality-of-life post-surgery and enhancing communication and decision-making in clinical practice. Their integration into routine care is vital for a holistic approach to lung cancer treatment, promising significant improvements in patient outcomes and quality of care.

9.
World J Clin Cases ; 12(22): 5245-5252, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39109047

RESUMEN

BACKGROUND: Gout and seronegative rheumatoid arthritis (SNRA) are two distinct inflammatory joint diseases whose co-occurrence is relatively infrequently reported. Limited information is available regarding the clinical management and prognosis of these combined diseases. CASE SUMMARY: A 57-year-old woman with a 20-year history of joint swelling, tenderness, and morning stiffness who was negative for rheumatoid factor and had a normal uric acid level was diagnosed with SNRA. The initial regimen of methotrexate, leflunomide, and celecoxib alleviated her symptoms, except for those associated with the knee. After symptom recurrence after medication cessation, her regimen was updated to include iguratimod, methotrexate, methylprednisolone, and folic acid, but her knee issues persisted. Minimally invasive needle-knife scope therapy revealed proliferating pannus and needle-shaped crystals in the knee, indicating coexistent SNRA and atypical knee gout. After postarthroscopic surgery to remove the synovium and urate crystals, and following a tailored regimen of methotrexate, leflunomide, celecoxib, benzbromarone, and allopurinol, her knee symptoms were significantly alleviated with no recurrence observed over a period of more than one year, indicating successful management of both conditions. CONCLUSION: This study reports the case of a patient concurrently afflicted with atypical gout of the knee and SNRA and underscores the significance of minimally invasive joint techniques as effective diagnostic and therapeutic tools in the field of rheumatology and immunology.

10.
Environ Sci Technol ; 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39133145

RESUMEN

In the pursuit of carbon neutrality, China's 2060 targets have been largely anchored in reducing greenhouse gas emissions, with less emphasis on the consequential benefits for air quality and public health. This study pivots to this critical nexus, exploring how China's carbon neutrality aligns with the World Health Organization's air quality guidelines (WHO AQG) regarding fine particulate matter (PM2.5) exposure. Coupling a technology-rich integrated assessment model, an emission-concentration response surface model, and exposure and health assessment, we find that decarbonization reduces sulfur dioxide (SO2), nitrogen oxides (NOx), and PM2.5 emissions by more than 90%; reduces nonmethane volatile organic compounds (NMVOCs) by more than 50%; and simultaneously reduces the disparities across regions. Critically, our analysis reveals that further targeted reductions in air pollutants, notably NH3 and non-energy-related NMVOCs, could bring most Chinese cities into attainment of WHO AQG for PM2.5 5 to 10 years earlier than the pathway focused solely on carbon neutrality. Thus, the integration of air pollution control measures into carbon neutrality strategies will present a significant opportunity for China to attain health and environmental equality.

11.
Kaohsiung J Med Sci ; 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39210603

RESUMEN

This study aimed to investigate the role of cluster of differentiation 276 (CD276) in evaluating the prognosis of clear cell renal carcinoma (ccRCC) and to build a nomogram for predicting ccRCC progression post-surgery. Using data downloaded from The Cancer Genome Atlas (TCGA) database, we constructed a Kaplan-Meier (KM) curve depicting the relationship between CD276 expression levels and the progression-free interval (PFI) in 539 ccRCC cases. We further validated this by plotting a KM curve of the relationship between CD276 expression levels and PFI in 116 ccRCC patients from our hospital. Using clinical data collected from 116 patients, we identified independent risk factors affecting postoperative PFI in patients with ccRCC through univariate and multivariate COX analyses and created a nomogram for visual representation. Both TCGA and clinical data revealed a negative correlation between the expression levels of CD276 and PFI (p < 0.05). Univariate COX analysis revealed that the prognostic nutritional index, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic inflammatory index, World Health Organization grading, tumor diameter, CD276 expression levels, T stage, and N stage were related to PFI (p < 0.05). Furthermore, multivariate COX analysis indicated that tumor diameter and CD276 expression levels were independent risk factors for postoperative PFI in patients with ccRCC (p < 0.05). The calibration curve of the established nomogram exhibited a slope close to 1, with a Hosmer-Lemeshow goodness-of-fit test result of 2.335 and a p-value of 0.311. In patients with ccRCC, a negative correlation was noted between tumor CD276 expression and PFI. The larger the tumor diameter and the higher the tumor CD276 expression level, the shorter is the PFI.

12.
J Pharmacol Exp Ther ; 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39168650

RESUMEN

Genetic loss-of-function mutations of Nav1.7 channel, abundantly expressed in peripheral nociceptive neurons, cause congenital insensitivity to pain (CIP) in humans, indicating that selective inhibition of the channel may lead to potential therapy of pain disorders. In this study, we investigated a novel compound, 5-chloro-N-(cyclopropylsulfonyl)-2-fluoro-4-(2-(8-(furan-2-ylmethyl)-8-azaspiro [4.5] decan-2-yl) ethoxy) benzamide (QLS-278) that inhibits Nav1.7 channel and exhibits anti-nociceptive activity. Compound QLS-278 exhibits inactivation- and concentration-dependent inhibition of macroscopic currents of Nav1.7 channels stably expressed in HEK293 cells with an IC50 of 1.2 {plus minus} 0.2 µM. QLS-278 causes a hyperpolarization shift of the channel inactivation and delays recovery from inactivation, without an obvious effect on voltage-dependent activation. In mouse DRG neurons, QLS-278 suppresses native TTX-sensitive Nav currents and also reduces neuronal firing. Moreover, QLS-278 dose-dependently relieves neuropathic pain induced by spared nerve injury and inflammatory pain induced by formalin without significant alteration of spontaneous locomotor activity in mice. Altogether, our identification of the novel compound QLS-278 may hold developmental potential for the treatment of chronic pain. Significance Statement QLS-278, a novel voltage-gated sodium Nav1.7 channel blocker, inhibits native TTX-S Na+ current and reduces action potential firings in DRG sensory neurons. QLS-278 also exhibits antinociceptive activity in mouse models of pain, thus demonstrating potential for the development of a treatment for chronic pain.

13.
Angew Chem Int Ed Engl ; : e202414720, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39166363

RESUMEN

Phase control over cation exchange (CE) reactions has emerged as an important approach for the synthesis of nanomaterials (NMs). Although factors such as crystal structure and morphology have been studied for the phase engineering of CE reactions in NMs, there remains a lack of systematic investigation to reveal the impact factors in heterogeneous materials. Herein, we report a molybdenum disulfide induced phase control method for synthesizing multidimensional Co3S4-MoS2 heteronanostructures (HNs) via cation exchange. MoS2 in parent Cu1.94S-MoS2 HNs are proved to affect the thermodynamics and kinetics of CE reactions, and facilitate the formation of Co3S4-MoS2 HNs with controlled phase. This MoS2 induced phase control method can be extended to other parent HNs with multiple dimensions, which shows its universality. Further, theoretical calculations demonstrate that Co3S4 (111)/MoS2 (001) exhibits a higher adhesion work, providing further evidence that MoS2 enables phase control in the HNs CE reactions, inducing the generation of novel Co3S4-MoS2 HNs. As a proof-of-concept application, the obtained Co3S4-MoS2 heteronanoplates (HNPls) show remarkable performance in hydrogen evolution reactions (HER) under alkaline media. This synthetic methodology provides a unique way to control the crystal structure and fills the gap in the study of heterogeneous materials on CE reaction over phase engineering.

14.
Zool Res ; 45(4): 833-844, 2024 07 18.
Artículo en Inglés | MEDLINE | ID: mdl-39004861

RESUMEN

Porcine reproductive and respiratory syndrome (PRRS) is a globally prevalent contagious disease caused by the positive-strand RNA PRRS virus (PRRSV), resulting in substantial economic losses in the swine industry. Modifying the CD163 SRCR5 domain, either through deletion or substitution, can eff1ectively confer resistance to PRRSV infection in pigs. However, large fragment modifications in pigs inevitably raise concerns about potential adverse effects on growth performance. Reducing the impact of genetic modifications on normal physiological functions is a promising direction for developing PRRSV-resistant pigs. In the current study, we identified a specific functional amino acid in CD163 that influences PRRSV proliferation. Viral infection experiments conducted on Marc145 and PK-15 CD163 cells illustrated that the mE535G or corresponding pE529G mutations markedly inhibited highly pathogenic PRRSV (HP-PRRSV) proliferation by preventing viral binding and entry. Furthermore, individual viral challenge tests revealed that pigs with the E529G mutation had viral loads two orders of magnitude lower than wild-type (WT) pigs, confirming effective resistance to HP-PRRSV. Examination of the physiological indicators and scavenger function of CD163 verified no significant differences between the WT and E529G pigs. These findings suggest that E529G pigs can be used for breeding PRRSV-resistant pigs, providing novel insights into controlling future PRRSV outbreaks.


Asunto(s)
Antígenos CD , Antígenos de Diferenciación Mielomonocítica , Mutación Puntual , Síndrome Respiratorio y de la Reproducción Porcina , Virus del Síndrome Respiratorio y Reproductivo Porcino , Receptores de Superficie Celular , Animales , Porcinos , Síndrome Respiratorio y de la Reproducción Porcina/genética , Síndrome Respiratorio y de la Reproducción Porcina/virología , Virus del Síndrome Respiratorio y Reproductivo Porcino/fisiología , Virus del Síndrome Respiratorio y Reproductivo Porcino/genética , Antígenos de Diferenciación Mielomonocítica/genética , Antígenos de Diferenciación Mielomonocítica/metabolismo , Antígenos CD/genética , Antígenos CD/metabolismo , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/metabolismo , Animales Modificados Genéticamente/genética , Línea Celular
15.
Aquat Toxicol ; 273: 107015, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38996482

RESUMEN

Nitrite, a highly toxic environmental contaminant, induces various physiological toxicities in aquatic animals. Herein, we investigate the in vivo effects of nitrite exposure at concentrations of 0, 0.2, 2, and 20 mg/L on glucose and lipid metabolism in zebrafish. Our results showed that exposure to nitrite induced mitochondrial oxidative stress in zebrafish liver and ZFL cells, which were evidenced by increased levels of malondialdehyde (MDA) and reactive oxygen species (ROS) as well as decreased mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP). Changes in these oxidative stress markers were accompanied by alterations in the expression levels of genes involved in HIF-1α pathway (hif1α and phd), which subsequently led to the upregulation of glycolysis and gluconeogenesis-related genes (gk, pklr, pdk1, pepck, g6pca, ppp1r3cb, pgm1, gys1 and gys2), resulting in disrupted glucose metabolism. Moreover, nitrite exposure activated ERs (Endoplasmic Reticulum stress) responses through upregulating of genes (atf6, ern1 and xbp1s), leading to increased expression of lipolysis genes (pparα, cpt1aa and atgl) and decreased expression of lipid synthesis genes (srebf1, srebf2, fasn, acaca, scd, hmgcra and hmgcs1). These results were also in consistent with the observed changes in glycogen, lactate and decreased total triglyceride (TG) and total cholesterol (TC) in the liver of zebrafish. Our in vitro results showed that co-treatment with Mito-TEMPO and nitrite attenuated nitrite-induced oxidative stress and improved mitochondrial function, which were indicated by the restorations of ROS, MMP, ATP production, and glucose-related gene expression recovered. Co-treatment of TUDCA and nitrite prevented nitrite-induced ERs response and which was proved by the levels of TG and TC ameliorated as well as the expression levels of lipid metabolism-related genes. In conclusion, our study suggested that nitrite exposure disrupted hepatic glucose and lipid metabolism through mitochondrial dysfunction and ERs responses. These findings contribute to the understanding of the potential hepatotoxicity for aquatic animals in the presence of ambient nitrite.


Asunto(s)
Estrés del Retículo Endoplásmico , Glucosa , Metabolismo de los Lípidos , Hígado , Nitritos , Estrés Oxidativo , Contaminantes Químicos del Agua , Pez Cebra , Animales , Glucosa/metabolismo , Nitritos/toxicidad , Hígado/efectos de los fármacos , Hígado/metabolismo , Estrés del Retículo Endoplásmico/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Metabolismo de los Lípidos/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Trastornos del Metabolismo de los Lípidos/inducido químicamente , Trastornos del Metabolismo de los Lípidos/genética
16.
Cells ; 13(13)2024 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-38995009

RESUMEN

We developed an automated microregistration method that enables repeated in vivo skin microscopy imaging of the same tissue microlocation and specific cells over a long period of days and weeks with unprecedented precision. Applying this method in conjunction with an in vivo multimodality multiphoton microscope, the behavior of human skin cells such as cell proliferation, melanin upward migration, blood flow dynamics, and epidermal thickness adaptation can be recorded over time, facilitating quantitative cellular dynamics analysis. We demonstrated the usefulness of this method in a skin biology study by successfully monitoring skin cellular responses for a period of two weeks following an acute exposure to ultraviolet light.


Asunto(s)
Piel , Humanos , Piel/citología , Piel/diagnóstico por imagen , Rayos Ultravioleta , Rastreo Celular/métodos , Proliferación Celular , Movimiento Celular , Microscopía de Fluorescencia por Excitación Multifotónica/métodos , Microscopía/métodos
17.
Nano Lett ; 24(29): 8887-8893, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-38984749

RESUMEN

The synthesis of transition metal nitrides nanocrystals (TMNs NCs) has posed a significant challenge due to the limited reactivity of nitrogen sources at lower temperatures and the scarcity of available synthesis methods. In this study, we present a novel colloidal synthesis strategy for the fabrication of Cu3N nanorods (NRs). It is found that the trace oxygen (O2) plays an important role in the synthesis process. And a new mechanism for the formation of Cu3N is proposed. Subsequently, by employing secondary lateral epitaxial growth, the Cu3N-Cu2O heteronanostructures (HNs) can be prepared. The Cu3N NRs and Cu3N-Cu2O HNs were evaluated as precursor electrocatalysts for the CO2 reduction reaction (CO2RR). The Cu3N-Cu2O HNs demonstrate remarkable selectivity and stability with ethylene (C2H4) Faradaic efficiency (FE) up to 55.3%, surpassing that of Cu3N NRs. This study provides innovative insights into the reaction mechanism of colloidal synthesis of TMNs NCs and presents alternative options for designing cost-effective electrocatalysts to achieve carbon neutrality.

18.
Toxicon ; 247: 107843, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-38964621

RESUMEN

BACKGROUND: Taiwan habu (Protobothrops mucrosquamatus), green bamboo viper (Viridovipera stejnegeri), and Taiwan cobra (Naja atra) are the most venomous snakebites in Taiwan. Patients commonly present with limb swelling but misdiagnosis rates are high, and currently available diagnostic tools are limited. This study explores the immune responses in snakebite patients to aid in differential diagnosis. METHODS: This prospective observational study investigated the changes in cytokines in snakebite patients and their potential for diagnosis. RESULTS: Elevated pro-inflammatory cytokines IL-6 and TNF-α were observed in all snakebite patients compared to the healthy control group. While no significant disparities were observed in humoral immune response cytokines, there were significant differences in IFN-γ levels, with significantly higher IL-10 levels in patients bitten by cobras. Patients with TNF-α levels exceeding 3.02 pg/mL were more likely to have been bitten by a cobra. CONCLUSION: This study sheds light on the immune responses triggered by various venomous snakebites, emphasizing the potential of cytokine patterns for snakebite-type differentiation. Larger studies are needed to validate these findings for clinical use, ultimately improving snakebite diagnosis and treatment.


Asunto(s)
Citocinas , Mordeduras de Serpientes , Humanos , Taiwán , Animales , Citocinas/sangre , Estudios Prospectivos , Adulto , Masculino , Persona de Mediana Edad , Femenino , Factor de Necrosis Tumoral alfa , Viperidae , Interleucina-6/sangre , Anciano
19.
NPJ Clim Action ; 3(1): 63, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39070178

RESUMEN

Under the next cycle of target setting under the Paris Agreement, countries will be updating and submitting new nationally determined contributions (NDCs) over the coming year. To this end, there is a growing need for the United States to assess potential pathways toward a new, maximally ambitious 2035 NDC. In this study, we use an integrated assessment model with state-level detail to model existing policies from both federal and non-federal actors, including the Inflation Reduction Act, Bipartisan Infrastructure Law, and key state policies, across all sectors and gases. Additionally, we develop a high-ambition scenario, which includes new and enhanced policies from these actors. We find that existing policies can reduce net greenhouse gas (GHG) emissions by 44% (with a range of 37% to 52%) by 2035, relative to 2005 levels. The high-ambition scenario can deliver net GHG reductions up to 65% (with a range of 59% to 71%) by 2035 under accelerated implementation of federal regulations and investments, as well as state policies such as renewable portfolio standards, EV sales targets, and zero-emission appliance standards. This level of reductions would provide a basis for continued progress toward the country's 2050 net-zero emissions goal.

20.
Pharmacol Biochem Behav ; 243: 173827, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39038728

RESUMEN

Alcohol-related cognitive impairment (ARCI) is highly prevalent among patients with alcohol abuse and dependence. The pathophysiology of ARCI, pivotal for refined therapeutic approaches, is not fully elucidated, posing a risk of progression to severe neurological sequelae such as Korsakoff's syndrome (KS) and Alcohol-Related Dementia (ARD). This study ventures into the underlying mechanisms of chronic alcohol-induced neurotoxicity, notably glutamate excitotoxicity and cytoskeletal disruption, and explores the therapeutic potential of Memantine, a non-competitive antagonist of the N-methyl-d-aspartate (NMDA) receptor known for its neuroprotective effect against excitotoxicity. Our investigation centers on the efficacy of Memantine in mitigating chronic alcohol-induced cognitive and hippocampal damages in vivo. Male C57BL/6J mice were subjected to 30 % (v/v, 6.0 g/kg) ethanol via intragastric administration alongside Memantine co-treatment (10 mg/kg/day, intraperitoneally) for six weeks. The assessment involved Y maze, Morris water maze, and novel object recognition tests to evaluate spatial and recognition memory deficits. Histopathological evaluations of the hippocampus were conducted to examine the extent of alcohol-induced morphological changes and the potential protective effect of Memantine. The findings reveal that Memantine significantly improves chronic alcohol-compromised cognitive functions and mitigates hippocampal pathological changes, implicating a moderating effect on the disassembly of actin cytoskeleton and microtubules in the hippocampus, induced by chronic alcohol exposure. Our results underscore Memantine's capability to attenuate chronic alcohol-induced cognitive and hippocampal morphological harm may partly through regulating cytoskeleton dynamics, offering valuable insights into innovative therapeutic strategies for ARCI.


Asunto(s)
Disfunción Cognitiva , Modelos Animales de Enfermedad , Hipocampo , Memantina , Ratones Endogámicos C57BL , Animales , Memantina/farmacología , Masculino , Ratones , Hipocampo/efectos de los fármacos , Hipocampo/patología , Hipocampo/metabolismo , Disfunción Cognitiva/tratamiento farmacológico , Etanol/toxicidad , Etanol/administración & dosificación , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/administración & dosificación , Alcoholismo/tratamiento farmacológico , Alcoholismo/patología , Alcoholismo/complicaciones , Aprendizaje por Laberinto/efectos de los fármacos , Antagonistas de Aminoácidos Excitadores/farmacología , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Receptores de N-Metil-D-Aspartato/metabolismo
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