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INTRODUCTION: Taurine is a naturally occurring sulfonic acid involved in various physiological and pathological processes, such as the regulation of calcium signaling, immune function, inflammatory response, and cellular aging. It has the potential to predict tumor malignant transformation and formation. Our previous work discovered the elevated taurine in lung cancer patients. However, the precise impact and mechanism of elevated serum taurine levels on lung cancer progression and the suitability of taurine or taurine-containing drinks for lung cancer patients remain unclear. OBJECTIVES: Our study aimed to systematically investigate the role of taurine in lung cancer, with the ultimate goal of contributing novel strategies for lung cancer treatment. METHODS: Lung cancer C57 and nude mice models, RNA sequencing, and stable transfection were applied to explored the effects and mechanisms of taurine on lung cancer. Tissues of 129 non-small cell lung cancer (NSCLC) patients derived from 2014 to 2017 for immunohistochemistry were collected in Taihe Hospital. RESULTS: Low doses of taurine, as well as taurine-infused beverages at equivalent doses, significantly enhanced lung tumor growth. Equally intriguing is that the promoting effect of taurine on lung cancer progression wanes as the dosage increases. The Nuclear factor erythroid 2-like 1 (Nfe2l1 or Nrf1)-reactive oxygen species (ROS)-PD-1 axis may be a potential mechanism for dual role of taurine in lung cancer progression. However, taurine's impacts on lung cancer progression and the anti-tumor function of Nfe2l1 were mainly determined by the immune competence. Taurine inhitited lung tumor growth probably by inhibiting NF-κB-mediated inflammatory responses in nude mice rather than by affecting Nfe2l1 function. As patients age increased, Nfe2l1 gene and protein gradually returned to the levels observed in healthy individuals, but lost its anti-lung cancer effects. CONCLUSIONS: Taurine emerges as a potential biomarker for lung cancer progression, predicting poor prognosis and unsuitability for specific patients. Lung cancer patients, especially young patients, should be conscious of potential effects of taurine-containing drinks. Conversely, taurine or its drinks may be more suitable for older or immune-deficient patients.

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A comprehensive understanding of physio-pathological processes necessitates non-invasive intravital three-dimensional (3D) imaging over varying spatial and temporal scales. However, huge data throughput, optical heterogeneity, surface irregularity, and phototoxicity pose great challenges, leading to an inevitable trade-off between volume size, resolution, speed, sample health, and system complexity. Here, we introduce a compact real-time, ultra-large-scale, high-resolution 3D mesoscope (RUSH3D), achieving uniform resolutions of 2.6 × 2.6 × 6 µm3 across a volume of 8,000 × 6,000 × 400 µm3 at 20 Hz with low phototoxicity. Through the integration of multiple computational imaging techniques, RUSH3D facilitates a 13-fold improvement in data throughput and an orders-of-magnitude reduction in system size and cost. With these advantages, we observed premovement neural activity and cross-day visual representational drift across the mouse cortex, the formation and progression of multiple germinal centers in mouse inguinal lymph nodes, and heterogeneous immune responses following traumatic brain injury-all at single-cell resolution, opening up a horizon for intravital mesoscale study of large-scale intercellular interactions at the organ level.

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OBJECTIVE: The objective of this study is to investigate the presence of astrocyte antibodies in patients, excluding aquaporin-4 or glial fibrillary acidic protein (GFAP) antibodies, while evaluating associated biomarkers and pathologies. METHODS: Patient serum and cerebrospinal fluid (CSF) were tested for antibodies using tissue- and cell-based assays. Neurofilament light chain (NFL) and GFAP in the CSF were detected using single-molecule array (SIMOA). RESULTS: 116 patients accepted SIMOA. Fifteen functional neurological disorders patients without antibodies were designated as controls. Thirty-five patients were positive for astrocyte antibodies (Anti-GFAP: 7; Anti-AQP4: 7; unknown antibodies: 21, designed as the double-negative group, DNAP). The most frequent phenotype of DNAP was encephalitis (42.9%), followed by myelitis (23.8%), movement disorders (19.0%), and amyotrophic lateral sclerosis-like (ALS-like) disease (14.2%). The levels of CSF GFAP and NFL in DNAP were higher than in the control (GFAP: 1967.29 [776.60-13214.47] vs 475.38 [16.80-943.60] pg/mL, p < 0.001; NFL: 549.11 [162.08-2462.61] vs 214.18 [81.60-349.60] pg/mL, p = 0.002). GFAP levels decreased in DNAP (n = 5) after immunotherapy (2446.75 [1583.45-6277.33] vs 1380.46 [272.16-2005.80] pg/mL, p = 0.043), while there was no difference in NFL levels (2273.78 [162.08-2462.61] vs 890.42 [645.06-3168.06] pg/mL, p = 0.893). Two brain biopsy patterns were observed: one exhibited prominent tissue proliferation and hypertrophic astrocytes, with local loss of astrocytes, while the other showed severe astrocyte depletion with loss of neurofilaments around the vessels. Eighteen patients received immunotherapy, and improved except one with ALS-like symptoms. We identified anti-vimentin in this patient. DISCUSSION: There are unidentified astrocyte antibodies. The manifestations of double-negativity are heterogeneous; nevertheless, the pathology and biomarkers remain consistent with astrocytopathy. Immunotherapy is effective.

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Acuaporina 4 , Astrocitos , Biomarcadores , Proteína Ácida Fibrilar de la Glía , Inmunoglobulina G , Humanos , Proteína Ácida Fibrilar de la Glía/líquido cefalorraquídeo , Proteína Ácida Fibrilar de la Glía/inmunología , Femenino , Masculino , Acuaporina 4/inmunología , Persona de Mediana Edad , Astrocitos/inmunología , Astrocitos/metabolismo , Astrocitos/patología , Estudios Retrospectivos , Adulto , Biomarcadores/líquido cefalorraquídeo , Biomarcadores/sangre , Anciano , Inmunoglobulina G/líquido cefalorraquídeo , Inmunoglobulina G/sangre , Proteínas de Neurofilamentos/líquido cefalorraquídeo , Proteínas de Neurofilamentos/sangre , Autoanticuerpos/líquido cefalorraquídeo , Autoanticuerpos/sangre , Adulto Joven , Adolescente

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The main cause of cancer-related fatalities is cancer metastasis to other body parts, and increased glycolysis is crucial for cancer cells to maintain their elevated levels of growth and energy requirements, ultimately facilitating the invasion and spread of tumors. The Warburg effect plays a significant role in the advancement of cancer, and focusing on the suppression of aerobic glycolysis could offer a promising strategy for anti-cancer treatment. Various glycolysis processes are associated with tumor metastasis, primarily involving non-coding RNA (ncRNAs), signaling pathways, transcription factors, and more. Various categories of noncoding RNAs, including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), have shown promise in influencing glucose metabolism associated with the spread of tumors. Additionally, circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) predominantly act as competitive endogenous RNAs (ceRNAs) by sequestering microRNAs, thereby modulating the expression of target genes and exerting significant influence on the metabolic processes of cancerous cells. Furthermore, the process of tumor metastasis through glycolysis also encompasses various signaling pathways (such as PI3K/AKT, HIF, Wnt/ß- Catenin, and ERK, among others) and transcription factors. This article delineates the primary mechanisms through which non-coding RNAs, signaling pathways, and transcription factors contribute to glycolysis in tumor metastasis. It also investigates the potential use of these factors as prognostic markers and targets for cancer treatment. The manuscript also explores the innovative applications of specific traditional Chinese medicine and clinical Western medications in inhibiting tumor spread through glycolysis mechanisms, offering potential as new candidates for anti-cancer drugs.

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The risk of Legionella transmission in built environments remains a significant concern. Legionella can spread within buildings through aerosol transmission, prompting the exploration of airborne transmission pathways and proposing corresponding prevention and control measures based on building characteristics. To this end, a comprehensive literature review on the transmission risk of Legionella in built environments was performed. Four electronic databases (PubMed, Web of Science, Google Scholar, and CNKI) were searched from inception to March 2024 for publications reporting the risk of Legionella transmission in built environments. Relevant articles and gray literature reports were hand-searched, and 96 studies were finally included. Legionella pollution comes from various sources, mainly originates in a variety of built environments in which human beings remain for extended periods. The sources, outbreaks, national standards, regulations, and monitoring techniques for Legionella in buildings are reviewed, in addition to increases in Legionella transmission risk due to poor maintenance of water systems and long-distance transmission events caused by aerosol characteristics. Air and water sampling using various analytical methods helps identify Legionella in the environment, recognize sources in the built environments, and control outbreaks. By comparing the standard regulations of national organizations globally, the authors further highlight gaps and deficiencies in Legionella surveillance in China. Such advancements offer essential insights and references for understanding and addressing Legionella transmission risk in the built environment, with the potential to contribute to safeguarding public health and building environment safety.

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Entorno Construido , Legionella , Legionella/aislamiento & purificación , Humanos , Legionelosis/transmisión , Legionelosis/prevención & control , Microbiología del Aire , Brotes de Enfermedades/prevención & control , Monitoreo del Ambiente , Microbiología del Agua , China/epidemiología

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CoMn2O4 (CMO) has been recognized as an effective peroxymonosulfate (PMS) activator; however, it still shows disadvantages such as limited reactive sites and metal leakage. Herein, an effective and environmentally friendly composite catalyst, CMO/Kln, was synthesized by anchoring CMO on kaolinite (Kln), a natural clay mineral with a special lamellar structure, to activate peroxymonosulfate (PMS) for the degradation of residue pharmaceuticals in water. The abundant hydroxyl groups located on the surface of Kln helped induce rich oxygen vacancies (OVs) into composite CMO/Kln, which not only acted as additional active sites but also accelerated working efficiency. In addition, compared with bare CMO, CMO/Kln showed lower crystallinity, and the adoption of the Kln substrate contributed to its structural stability with lower metal leaching after three rounds of reaction. The universal applicability of CMO/Kln was also verified by using three other pharmaceuticals as probes. This work shed light on the adoption of natural clay minerals in modifying CMO catalysts with promoted catalytic activity for the efficient and eco-friendly remediation of pharmaceuticals in wastewater.

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BACKGROUND: The effect of coronavirus disease 2019 (COVID-19) on adrenal endocrine metabolism in critically ill patients remains unclear. This study aimed to investigate the alterations in adrenal steroidogenic activity, elucidate underlying mechanisms, provide in situ histopathological evidence, and examine the clinical implications. METHODS: The comparative analyses of the adrenal cortices from 24 patients with fatal COVID-19 and 20 matched controls were performed, excluding patients previously treated with glucocorticoids. SARS-CoV-2 and its receptors were identified and pathological alterations were examined. Furthermore, histological examinations, immunohistochemical staining and ultrastructural analyses were performed to assess corticosteroid biosynthesis. The zona glomerulosa (ZG) and zona fasciculata (ZF) were then dissected for proteomic analyses. The biological processes that affected steroidogenesis were analyzed by integrating histological, proteomic, and clinical data. Finally, the immunoreactivity and responsive genes of mineralocorticoid and glucocorticoid receptors in essential tissues were quantitatively measured to evaluate corticosteroid responsiveness. FINDINGS: The demographic characteristics of COVID-19 patients were comparable with those of controls. SARS-CoV-2-like particles were identified in the adrenocortical cells of three patients; however, these particles did not affect cellular morphology or steroid synthesis compared with SARS-CoV-2-negative specimens. Although the adrenals exhibited focal necrosis, vacuolization, microthrombi, and inflammation, widespread degeneration was not evident. Notably, corticosteroid biosynthesis was significantly enhanced in both the ZG and ZF of COVID-19 patients. The increase in the inflammatory response and cellular differentiation in the adrenal cortices of patients with critical COVID-19 was positively correlated with heightened steroidogenic activity. Additionally, the appearance of more dual-ZG/ZF identity cells in COVID-19 adrenals was in accordance with the increased steroidogenic function. However, activated mineralocorticoid and glucocorticoid receptors and their responsive genes in vital tissues were markedly reduced in patients with critical COVID-19. INTERPRETATION: Critical COVID-19 was characterized by potentiated adrenal steroidogenesis, associated with increased inflammation, enhanced differentiation and elevated dual-ZG/ZF identity cells, alongside suppressed corticosteroid responsiveness. These alterations implied the reduced effectiveness of conventional corticosteroid therapy and underscored the need for evaluation of the adrenal axis and corticosteroid sensitivity.

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Corticoesteroides , COVID-19 , Enfermedad Crítica , Humanos , COVID-19/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Corticoesteroides/uso terapéutico , Corticoesteroides/biosíntesis , Anciano , SARS-CoV-2 , Zona Fascicular/metabolismo , Zona Fascicular/efectos de los fármacos , Receptores de Glucocorticoides/metabolismo , Adulto , Corteza Suprarrenal/metabolismo , Corteza Suprarrenal/efectos de los fármacos , Corteza Suprarrenal/patología , Zona Glomerular/metabolismo , Zona Glomerular/efectos de los fármacos , Zona Glomerular/patología , Glándulas Suprarrenales/metabolismo , Glándulas Suprarrenales/efectos de los fármacos

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Background: Puerperal infection is one of the four main causes of maternal mortality. A giant intrauterine mass caused by puerperal infection is a rare form of infection. The delay in treatment may result in the removal of the uterus. Case Presentation: We report a case of a large intrauterine mass resulting from puerperal infection, in which the uterus was salvaged through antibiotic treatment and curettage. The patient was a 27-year-old female, who presented with a large intrauterine mass, accompanied by fever and abdominal pain 35 days after vaginal delivery. The large intrauterine mass was ultimately pathologically confirmed to be necrotic smooth muscle tissue instead of residual pregnancy tissue. Conclusion: In most cases, the intrauterine mass after pregnancy is residual pregnancy tissue. Early identification and management are critical to ensure a good prognosis for patients. Obstetricians and pregnant women should be fully aware of the hazards of puerperal infections.

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AIMS: To establish a comprehensive understanding of the roles of midwives and the challenges they encounter in the prevention, diagnosis and management of postpartum haemorrhage (PPH) following normal vaginal delivery. DESIGN: We conducted a scoping review following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Scoping Reviews (PRISMA-ScR) recommendations. METHODS: We considered studies related to the roles of midwives and the challenges they encounter in the prevention, diagnosis and management of PPH during vaginal delivery. We excluded guidelines, consensuses, abstracts of meetings and non-English language studies. Databases, including the Cochrane Library, PubMed, Web of Science, Ovid, Medline, Embase, JBI EBP and BIOSIS Previews, were searched on January 1, 2023, with no time limitations. RESULTS: We included 28 publications. Midwives play important roles in the prevention, diagnosis and management of postpartum haemorrhage during vaginal delivery. In the prevention of PPH, midwives' roles include identifying and managing high-risk factors, managing labour and implementing skin-to-skin contact. In the diagnosis of PPH, midwives' roles include early recognition and blood loss estimation. In the management of PPH, midwives are involved in mobilizing other professional team members, emergency management, investigating causes, enhancing uterine contractions, the repair of perineal tears, arranging transfers and preparation for surgical intervention. However, midwives face substantial challenges, including insufficient knowledge and skills, poor teamwork skills, insufficient resources and the need to deal with their negative emotions. Midwives must improve their knowledge, skills and teamwork abilities. Health care system managers and the government should give full support to midwives. Future research should focus on developing clinical practice guidelines for midwives for preventing, diagnosing and managing postpartum haemorrhage.

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Parto Obstétrico , Hemorragia Posparto , Humanos , Hemorragia Posparto/enfermería , Hemorragia Posparto/prevención & control , Hemorragia Posparto/terapia , Femenino , Parto Obstétrico/efectos adversos , Parto Obstétrico/enfermería , Embarazo , Partería , Enfermeras Obstetrices

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Land use changes lead to changes in the functions of different types of carbon sources and sinks, which are key sources of carbon emissions. The study of carbon emissions and its influencing factors in the Aksu River Basin from the perspective of land use change is of great importance for the promotion of integrated protection and restoration of mountains, water, forests, fields, lakes, grasslands, sand, and ice in the basin and to help achieve the goal of carbon peaking and carbon neutrality. Based on four periods of land use data and socio-economic data from 1990 to 2020, the total carbon emissions from land use were measured, and the spatial and temporal trajectories of carbon emissions and their influencing factors were explored. The results showed that:① from 1990 to 2020, arable land, forest land, construction land, and unused land showed a general increasing trend, whereas grasslands and water areas showed a decreasing trend. The spatial change in land use types was mainly characterized by the conversion of grasslands and unused land into arable land, and 83.58 % of the arable land conversion areas were concentrated in the southwest of Wensu, Aksu, and the northern part of Awat. ② The total net carbon emissions in the basin showed a continuous growth trend from 1990 to 2020, with a cumulative increase of 14.78×104 t. The increase in arable land was a key factor causing an increase in net carbon emissions in the basin. ③ The spatial distribution pattern of land use carbon emissions in the basin was high in the middle and low in the fourth, with significant changes in net carbon emissions mainly in the southern part of Wensu, Aksu, Awat, and Alaer. ④ Human activities had the strongest driving effect on land use carbon emissions, with their effects gradually increasing from east to west. The contribution of average annual temperature to land use carbon emissions was mainly concentrated in the eastern part of Aksu and the northern part of Awat, whereas average annual rainfall had a strong inhibitory effect on the northern part of Wensu and the western part of Aheqi.

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Eleven alkaloids including four previously undescribed oxoisoaporphine alkaloids, menisoxoisoaporphines A-D (1-4), four known analogues (5-8), and three aporphine alkaloids (9-11), were isolated and identified from the rhizomes of Menispermum dauricum. Their structures were elucidated by extensive spectroscopic data and single-crystal X-ray diffraction analyses. Among them, compounds 1 and 4 were the first samples of oxoisoaporphine with C-6 isopentylamino moiety, and 2 was a rare C-4 methylation product of oxoisoaporphine alkaloid. The in vitro anti-inflammatory activity of compounds 1-11 was performed by evaluating the inhibition of NO level in LPS-induced RAW264.7 macrophages. Among them, compound 4 exhibited the most potent NO inhibition activity with an IC50 value of 1.95 ± 0.33 µM. The key structure-activity relationships of those oxoisoaporphine alkaloids for anti-inflammatory effects have been summarized.

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Alcaloides , Aporfinas , Menispermum , Óxido Nítrico , Ratones , Células RAW 264.7 , Animales , Relación Estructura-Actividad , Alcaloides/farmacología , Alcaloides/química , Alcaloides/aislamiento & purificación , Estructura Molecular , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Menispermum/química , Aporfinas/farmacología , Aporfinas/química , Aporfinas/aislamiento & purificación , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Lipopolisacáridos/farmacología , Lipopolisacáridos/antagonistas & inhibidores , Relación Dosis-Respuesta a Droga , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/aislamiento & purificación , Macrófagos/efectos de los fármacos

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Background: The prognostic value of an effective biomarker, pan-immune-inflammation value (PIV), for head and neck squamous cell carcinoma (HNSCC) patients after radical surgery or chemoradiotherapy has not been well explored. This study aimed to construct and validate nomograms based on PIV to predict survival outcomes of HNSCC patients. Methods: A total of 161 HNSCC patients who underwent radical surgery were enrolled retrospectively for development cohort. The cutoff of PIV was determined using the maximally selected rank statistics method. Multivariable Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were performed to develop two nomograms (Model A and Model B) that predict disease-free survival (DFS). The concordance index, receiver operating characteristic curves, calibration curves, and decision curve analysis were used to evaluate the nomograms. A cohort composed of 50 patients who received radiotherapy or chemoradiotherapy (RT/CRT) alone was applied for generality testing of PIV and nomograms. Results: Patients with higher PIV (≥123.3) experienced a worse DFS (HR, 5.01; 95% CI, 3.25-7.72; p<0.0001) and overall survival (OS) (HR, 5.23; 95% CI, 3.34-8.18; p<0.0001) compared to patients with lower PIV (<123.3) in the development cohort. Predictors of Model A included age, TNM stage, neutrophil-to-lymphocyte ratio (NLR), and PIV, and that of Model B included TNM stage, lymphocyte-to-monocyte ratio (LMR), and PIV. In comparison with TNM stage alone, the two nomograms demonstrated good calibration and discrimination and showed satisfactory clinical utility in internal validation. The generality testing results showed that higher PIV was also associated with worse survival outcomes in the RT/CRT cohort and the possibility that the two nomograms may have a universal applicability for patients with different treatments. Conclusions: The nomograms based on PIV, a simple but useful indicator, can provide prognosis prediction of individual HNSCC patients after radical surgery and may be broadly applicated for patients after RT/CRT alone.

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Three different iridium(III) complexes, labelled as Ir1-Ir3, each bearing a unique anchoring moiety (diethyl [2,2'-bipyridine]-4,4'-dicarboxylate, tetraethyl [2,2'-bipyridine]-4,4'-diylbis(phosphonate), or [2,2'-biquinoline]-4,4'-dicarboxylic acid), were synthesized to serve as photosensitizers. Their electrochemical and photophysical characteristics were systematically investigated. ERP measurements were employed to elucidate the impact of the anchoring groups on the photocatalytic hydrogen generation performance of the complexes. The novel iridium(III) complexes were integrated with platinized TiO2 (Pt-TiO2) nanoparticles and tested for their ability to catalyze hydrogen production under visible light. A H2 turnover number (TON) of up to 3670 was obtained upon irradiation for 120 h. The complexes with tetraethyl [2,2'-bipyridine]-4,4'-diylbis(phosphonate) anchoring groups were found to outperform those bearing other moieties, which may be one of the important steps in the development of high-efficiency iridium(III) photosensitizers for hydrogen generation by water splitting. Additionally, toxicological analyses found no significant difference in the toxicity to luminescent bacteria of any of the present iridium(III) complexes compared with that of TiO2, which implies that the complexes investigated in this study do not pose a high risk to the aquatic environment compared to TiO2.

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Currently, no effective vaccine to prevent human immunodeficiency virus (HIV) infection is available, and various platforms are being examined. The vesicular stomatitis virus (VSV) vaccine vehicle can induce robust humoral and cell-mediated immune responses, making it a suitable candidate for the development of an HIV vaccine. Here, we analyze the protective immunological impacts of recombinant VSV vaccine vectors that express chimeric HIV Envelope proteins (Env) in rhesus macaques. To improve the immunogenicity of these VSV-HIV Env vaccine candidates, we generated chimeric Envs containing the transmembrane and cytoplasmic tail of the simian immunodeficiency virus (SIV), which increases surface Env on the particle. Additionally, the Ebola virus glycoprotein was added to the VSV-HIV vaccine particles to divert tropism from CD4 T cells and enhance their replications both in vitro and in vivo. Animals were boosted with DNA constructs that encoded matching antigens. Vaccinated animals developed non-neutralizing antibody responses against both the HIV Env and the Ebola virus glycoprotein (EBOV GP) as well as systemic memory T-cell activation. However, these responses were not associated with observable protection against simian-HIV (SHIV) infection following repeated high-dose intra-rectal SHIV SF162p3 challenges.

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The fluid loss additive is to prevent the cement slurry from filtrating water to the formation under pressure. 2-Acrylamido-2-methylpropanesulfonic acid (AMPS)-based fluid loss additive mainly works by adsorbing on the surface of cement particles. The adsorption affects cement hydration. In this paper, the effect of one kind of AMPS-based fluid loss additive (A-FLA) on the hydration of oil well cement was studied. The water loss, setting time, thickening time, and compressive strength of cement slurry with various amounts of FLA were measured. In addition, the hydration heat of the cement slurry, FLA adsorption isotherm on cement particles, and hydration minerals were studied. The results showed that A-FLA had a good water loss control ability. The water loss of the cement slurry decreased slowly with the increase of A-FLA dosage when the adsorption capacity exceeded 4.47 mg/g. The low adsorption capacity of A-FLA (less than 4.47 mg/g) had a significant impact on the thickening time. With an adsorption capacity greater than 4.47 mg/g, the thickening time varied minimally. A-FLA mainly delayed the hydration of C3S at 1 day and reduced the production amorphous phase.

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Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic (DA) neurons and aggregation of α-synuclein (α-syn). Ferroptosis, a form of cell death induced by iron accumulation and lipid peroxidation, is involved in the pathogenesis of PD. It is unknown whether melatonin receptor 1 (MT1) modulates α-syn and ferroptosis in PD. Here, we used α-syn preformed fibrils (PFFs) to induce PD models in vivo and in vitro. In PD mice, α-syn aggregation led to increased iron deposition and ferroptosis. MT1 knockout exacerbated these changes and resulted in more DA neuronal loss and severe motor impairment. MT1 knockout also suppressed the Sirt1/Nrf2/Ho1/Gpx4 pathway, reducing resistance to ferroptosis, and inhibited expression of ferritin Fth1, leading to more release of ferrous ions. In vitro experiments confirmed these findings. Knockdown of MT1 enhanced α-syn PFF-induced intracellular α-syn aggregation and suppressed expression of the Sirt1/Nrf2/Ho1/Gpx4 pathway and Fth1 protein, thereby aggravating ferroptosis. Conversely, overexpression of MT1 reversed these effects. Our findings reveal a novel mechanism by which MT1 activation prevents α-syn-induced ferroptosis in PD, highlighting the neuroprotective role of MT1 in PD.

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Ferroptosis , Melatonina , Enfermedad de Parkinson , Ratones , Animales , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/patología , alfa-Sinucleína/metabolismo , alfa-Sinucleína/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Melatonina/farmacología , Receptor de Melatonina MT1/metabolismo , Sirtuina 1/metabolismo , Neuronas Dopaminérgicas , Hierro/metabolismo

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Aberrant adrenal function has been frequently reported in COVID-19 patients, but histopathological evidence remains limited. This retrospective autopsy study aims to scrutinize the impact of COVID-19 duration on adrenocortical zonational architecture and peripheral corticosteroid reactivity. The adrenal glands procured from 15 long intensive care unit (ICU)-stay COVID-19 patients, 9 short ICU-stay COVID-19 patients, and 20 matched controls. Subjects who had received glucocorticoid treatment prior to sampling were excluded. Applying hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining, we disclosed that the adrenocortical zonational structure was substantially disorganized in COVID-19 patients, which long ICU-stay patients manifested a higher prevalence of severe disorganization (67%) than short ICU-stay patients (11%; P = 0.0058). The adrenal cortex of COVID-19 patients exhibited a 40% decrease in the zona glomerulosa (ZG) area and a 74% increase in the zona fasciculata (ZF) area (both P < 0.0001) relative to controls. Furthermore, among long ICU-stay COVID-19 patients, the ZG area diminished by 31% (P = 0.0004), and the ZF area expanded by 27% (P = 0.0004) in comparison to short ICU-stay patients. The zona reticularis (ZR) area remained unaltered. Nuclear translocation of corticosteroid receptors in the liver and kidney of long ICU-stay COVID-19 patients was at least 43% lower than in short ICU-stay patients (both P < 0.05). These findings underscore the necessity for clinicians to monitor adrenal function in long-stay COVID-19 patients.

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Corteza Suprarrenal , COVID-19 , Humanos , Enfermedad Crítica , Estudios Retrospectivos , Glándulas Suprarrenales , Corticoesteroides

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BACKGROUND: Non-small cell lung cancer (NSCLC) remains at the forefront of new cancer cases, and there is an urgent need to find new treatments or improve the efficacy of existing therapies. In addition to the application in the field of cerebrovascular diseases, recent studies have revealed that tanshinone IIA (Tan IIA) has anticancer activity in a variety of cancers. PURPOSE: To investigate the potential anticancer mechanism of Tan IIA and its impact on immunotherapy in NSCLC. METHODS: Cytotoxicity and colony formation assays were used to detect the Tan IIA inhibitory effect on NSCLC cells. This research clarified the mechanisms of Tan IIA in anti-tumor and programmed death-ligand 1 (PD-L1) regulation by using flow cytometry, transient transfection, western blotting and immunohistochemistry (IHC) methods. Besides, IHC was also used to analyze the nuclear factor of activated T cells 1 (NFAT2) expression in NSCLC clinical samples. Two animal models including xenograft mouse model and Lewis lung cancer model were used for evaluating tumor suppressive efficacy of Tan IIA. We also tested the efficacy of Tan IIA combined with programmed cell death protein 1 (PD-1) inhibitors in Lewis lung cancer model. RESULTS: Tan IIA exhibited good NSCLC inhibitory effect which was accompanied by endoplasmic reticulum (ER) stress response and increasing Ca2+ levels. Moreover, Tan IIA could suppress the NFAT2/ Myc proto oncogene protein (c-Myc) signaling, and it also was able to control the Jun Proto-Oncogene(c-Jun)/PD-L1 axis in NSCLC cells through the c-Jun N-terminal kinase (JNK) pathway. High NFAT2 levels were potential factors for poor prognosis in NSCLC patients. Finally, animal experiments data showed a stronger immune activation phenotype, when we performed treatment of Tan IIA combined with PD-1 monoclonal antibody. CONCLUSION: The findings of our research suggested a novel mechanism for Tan IIA to inhibit NSCLC, which could exert anti-cancer effects through the JNK/NFAT2/c-Myc pathway. Furthermore, Tan IIA could regulate tumor PD-L1 levels and has the potential to improve the efficacy of PD-1 inhibitors.

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Abietanos , Carcinoma de Pulmón de Células no Pequeñas , Estrés del Retículo Endoplásmico , Neoplasias Pulmonares , Factores de Transcripción NFATC , Abietanos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Animales , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Estrés del Retículo Endoplásmico/efectos de los fármacos , Ratones , Factores de Transcripción NFATC/metabolismo , Línea Celular Tumoral , Antineoplásicos Fitogénicos/farmacología , Proto-Oncogenes Mas , Antígeno B7-H1/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , Receptor de Muerte Celular Programada 1 , Inmunoterapia/métodos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Células A549 , Ratones Desnudos , Ratones Endogámicos BALB C , Proteínas Proto-Oncogénicas c-myc/metabolismo , Masculino , Femenino

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Mammals exhibit different rates of cancer, with long-lived species generally showing greater resistance. Although bats have been suggested to be resistant to cancer due to their longevity, this has yet to be systematically examined. Here, we investigate cancer resistance across seven bat species by activating oncogenic genes in their primary cells. Both in vitro and in vivo experiments suggest that Myotis pilosus (MPI) is particularly resistant to cancer. The transcriptomic and functional analyses reveal that the downregulation of three genes (HIF1A, COPS5, and RPS3) largely contributes to cancer resistance in MPI. Further, we identify the loss of a potential enhancer containing the HIF1A binding site upstream of COPS5 in MPI, resulting in the downregulation of COPS5. These findings not only provide direct experimental evidence for cancer resistance in a bat species but also offer insights into the natural mechanisms of cancer resistance in mammals.

Asunto(s)

Quirópteros , Neoplasias , Animales , Humanos , Quirópteros/genética , Mamíferos/genética , Transcriptoma , Perfilación de la Expresión Génica , Neoplasias/genética

RESUMEN

Accurately predicting future carbon emissions is of great significance for the government to scientifically promote carbon emission reduction policies. Among the current technologies for forecasting carbon emissions, the most prominent ones are econometric models and deep learning, but few works have systematically compared and analyzed the forecasting performance of the methods. Therefore, the paper makes a comparison for deep learning model, machine learning model, and the econometric model to demonstrate whether deep learning is an efficient method for carbon emission prediction research. In model mechanism, neural network for deep learning refers to an information processing model established by simulating biological neural system, and the model can be further extended through bionic characteristics. So the paper further optimizes the model from the perspective of bionics and proposes an innovative deep learning model based on the memory behavior mechanism of group creatures. Comparison results show that the prediction accuracy of the heuristic neural network is higher than that of the econometric model. Through in-depth analysis, the heuristic neural network is more suitable for predicting future carbon emissions, while the econometric model is more suitable for clarifying the impact of influencing factors on carbon emissions.

Asunto(s)

Aprendizaje Profundo , Modelos Econométricos , Carbono , Aprendizaje Automático , Redes Neurales de la Computación , Predicción , China