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Digital reconstruction of the intricate 3D morphology of individual neurons from microscopic images is a crucial challenge in both individual laboratories and large-scale projects focusing on cell types and brain anatomy. This task often fails in both conventional manual reconstruction and state-of-the-art artificial intelligence (AI)-based automatic reconstruction algorithms. It is also challenging to organize multiple neuroanatomists to generate and cross-validate biologically relevant and mutually agreed upon reconstructions in large-scale data production. Based on collaborative group intelligence augmented by AI, we developed a collaborative augmented reconstruction (CAR) platform for neuron reconstruction at scale. This platform allows for immersive interaction and efficient collaborative editing of neuron anatomy using a variety of devices, such as desktop workstations, virtual reality headsets and mobile phones, enabling users to contribute anytime and anywhere and to take advantage of several AI-based automation tools. We tested CAR's applicability for challenging mouse and human neurons toward scaled and faithful data production.

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Long-term hyperuricemia can induce kidney damage, clinically referred to as hyperuricemic nephropathy (HN), which is characterized by renal fibrosis, inflammation, and oxidative stress. However, currently used uric acid-lowering drugs are not capable of protecting the kidneys from damage. Therefore, uric acid-lowering drugs that can also protect the kidneys are urgently needed. In this study, we first discovered that salinomycin, an antibiotic, can regulate uric acid homeostasis and ameliorate kidney damage in mice with HN. Mechanistically, salinomycin inhibited serum and hepatic xanthine oxidase (XOD) activities and downregulated renal urate transporter 1 (URAT1) expression and transport activity, thus exerting uric acid-lowering effects in mice with HN. Furthermore, we found that salinomycin promoted p-NRF2 Ser40 expression, resulting in increased nuclear translocation of NRF2 and activation of NRF2. More importantly, salinomycin affected the gut microbiota and promoted the generation of short-chain fatty acids (SCFAs) in mice with HN. In conclusion, our results revealed that salinomycin maintains uric acid homeostasis and alleviates kidney injury in mice with HN by multiple mechanisms, suggesting that salinomycin might be a desirable candidate for HN treatment in the clinic.

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Purpose: Given the increasing occurrence of stroke and high-sodium diets (DHIS) over the past 30 years, it is crucial to assess the global, national, and regional impact of DHIS on the burden of stroke. Methods and materials: The Global Burden of Diseases Study 2019 provided the study's data. We used the Bayesian meta-regression tool DisMod-MR 2.1 to evaluate the burden of stroke attributable to DHIS. Age-standardized disability-adjusted life years (ASDR) and age-standardized mortality rate (ASMR) were used to quantify the burden. We perform correlation analysis utilizing the Spearman rank-order correlation method, and we calculate the estimated annual percentage change (EAPC) to evaluate temporal trends. Results: Globally, DHIS accounts for 17,673.33 thousand disability-adjusted life years (DALYs) and 700.98 thousand deaths of stroke in 2019. The burden of stroke attributable to DHIS has declined between 1990 and 2019 globally and in the majority of regions, with the largest declines seen in regions with high sociodemographic indexes (SDI). Both ASMR and ASDR were higher regionally in regions with moderate SDI than those in developed regions. Furthermore, the absolute values of EAPC, reflecting the rate of decrease, were notably lower in these regions compared to developed nations. High-income North America, categorized within the SDI regions, notably witnessed the smallest decline in ASDR over the last three decades. Additionally, from 1990 to 2019, males consistently bore a larger burden of stroke attributable to DHIS. Conclusion: The burden of stroke attributable to DHIS remained a major concern despite advancements in public knowledge of stroke and their utilization of emergency medical services. Over the past 30 years, more burden has been placed on males and regions with moderate SDI values; in males, higher EAPC values for both ASMR and ASDR have been found. This underscores the urgent need for effective interventions to alleviate the burden of stroke associated with DHIS.

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Sepsis-related brain injury (SRBI) refers to brain dysfunction and structural damage caused by sepsis, which is characterized by inflammation, oxidative stress, and destruction of the blood-brain barrier. Pioglitazone is a PPAR-γ agonist in which PPAR-γ acts as an inflammatory modulator, determining the relationship between PPAR-γ and SRBI and inflammatory state is critical for the disease. This study aimed to construct a drug-target-disease network for SRBI and Pioglitazone based on network pharmacology, and to investigate the therapeutic effect and potential mechanism of Pioglitazone in SRBI induced by lipopolysaccharide (LPS) in rats through transcriptomics. To establish a rat Model of SRBI by intraperitoneal injection of LPS (10 mg/kg): SD rats were divided into Control, Model (LPS), Pioglitazone, (LPS + Pioglitazone) and GW9662 group (LPS+GW9662). The effects and potential mechanisms of Pioglitazone in the treatment of SRBI were studied using biochemical indexes, pathological changes and transcriptome-sequencing (RNA-seq). RNA-seq results showed 620 DEGs between the Model and the Pioglitazone groups. Enrichment analysis involved multiple inflammatory response processes and chemokine receptor binding functions. TLR4 and CXCL10 in the Toll signaling pathway may play an important role in SRBI as important targets. Pioglitazone may ameliorate SRBI through the PPAR-γ/TLR4/CXCL10 pathway.

Asunto(s)

Lipopolisacáridos , PPAR gamma , Pioglitazona , Ratas Sprague-Dawley , Sepsis , Transcriptoma , Pioglitazona/farmacología , Animales , Ratas , PPAR gamma/metabolismo , PPAR gamma/genética , Masculino , Transcriptoma/efectos de los fármacos , Sepsis/tratamiento farmacológico , Sepsis/genética , Sepsis/complicaciones , Sepsis/metabolismo , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 4/genética , Quimiocina CXCL10/genética , Quimiocina CXCL10/metabolismo , Modelos Animales de Enfermedad , Transducción de Señal/efectos de los fármacos , Anilidas/farmacología , Lesiones Encefálicas/tratamiento farmacológico , Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/genética , Lesiones Encefálicas/etiología , Perfilación de la Expresión Génica , Encefalopatía Asociada a la Sepsis/tratamiento farmacológico , Encefalopatía Asociada a la Sepsis/genética , Encefalopatía Asociada a la Sepsis/metabolismo

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Kopsileuconines A-D (1-4), four monoterpenoid bisindole alkaloids with unprecedented skeletons, along with their biosynthetically related precursors (5-8) were isolated from the roots of Kopsia hainanensis. Compound 1 possessed an undescribed C-6-C-5' dimerization pattern of aspidofractinine-type alkaloids. Compounds 2-4 were rhazinilam-kopsine (2) and rhazinilam-aspidofractinine type (3 and 4) bisindole alkaloids with undescribed skeletons, respectively. Their structures with absolute configurations were fully accomplished by extensive spectroscopic analysis, quantum-chemical calculations, and X-ray crystallography. A plausible biosynthetic pathway for 1-4 was proposed. Compound 2 exhibited a significant inhibitory effect against human lung cancer cell lines PC9 (EGFR mutant), with an IC50 value of 15.07 ± 1.19 µM.

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Antineoplásicos Fitogénicos , Apocynaceae , Ensayos de Selección de Medicamentos Antitumorales , Alcaloides Indólicos , Humanos , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Alcaloides Indólicos/química , Alcaloides Indólicos/farmacología , Alcaloides Indólicos/aislamiento & purificación , Apocynaceae/química , Estructura Molecular , Línea Celular Tumoral , Relación Estructura-Actividad , Proliferación Celular/efectos de los fármacos , Raíces de Plantas/química , Relación Dosis-Respuesta a Droga , Cristalografía por Rayos X

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Cortisol is a well-known stress biomarker; this study focuses on using electrochemical immuno-sensing to measure the concentration of cortisol selectively and sensitively in artificial samples. Anti-cortisol antibodies have been immobilised on polycrystalline Au electrodes via strong covalent thiol bonds, fabricating an electrochemical bio-immunosensor for cortisol detection. IrOx was then anodically electrodeposited as a reference electrode on a commercial screen-printed electrode and electrochemical impedance spectrometry (EIS) studies were used to correlate the electrochemical response to cortisol concentration and the induced changes in charge transfer resistance (Rct). A linear relationship between the Rct and the logarithm of cortisol concentration was found in concentrations ranging from 1 ng/mL to 1 mg/mL with limit of detection at 11.85 pg/mL (32.69 pM). The modification of the reference electrode with iridium oxide has greatly improved the reproducibility of the screen-printed electrode. The sensing system can provide a reliable and sensitive detection approach for cortisol measurements.

Asunto(s)

Técnicas Electroquímicas , Electrodos , Hidrocortisona , Iridio , Hidrocortisona/análisis , Iridio/química , Técnicas Electroquímicas/instrumentación , Técnicas Electroquímicas/métodos , Sistemas de Atención de Punto , Humanos , Límite de Detección , Oro/química , Técnicas Biosensibles/métodos

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The development of new antibiotics continues to pose challenges, particularly considering the growing threat of multidrug-resistant Staphylococcus aureus. Structurally diverse natural products provide a promising source of antibiotics. Herein, we outline a concise approach for the collective asymmetric total synthesis of polycyclic xanthene myrtucommulone D and five related congeners. The strategy involves rapid assembly of the challenging benzopyrano[2,3-a]xanthene core, highly diastereoselective establishment of three contiguous stereocenters through a retro-hemiketalization/double Michael cascade reaction, and a Mitsunobu-mediated chiral resolution approach with high optical purity and broad substrate scope. Quantum mechanical calculations provide insight into stereoselective construction mechanism of the three contiguous stereocenters. Additionally, this work leads to the discovery of an antibacterial agent against both drug-sensitive and drug-resistant S. aureus. This compound operates through a unique mechanism that promotes bacterial autolysis by activating the two-component sensory histidine kinase WalK. Our research holds potential for future antibacterial drug development.

Asunto(s)

Antibacterianos , Staphylococcus aureus Resistente a Meticilina , Xantenos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Xantenos/síntesis química , Xantenos/farmacología , Xantenos/química , Pruebas de Sensibilidad Microbiana , Estereoisomerismo , Compuestos Policíclicos/síntesis química , Compuestos Policíclicos/farmacología , Compuestos Policíclicos/química , Descubrimiento de Drogas , Estructura Molecular

RESUMEN

Eleven undescribed monoterpenoid bisindole alkaloids, alstomaphyines A-K (1-11), along with three known analogues were isolated from the leaves and stem bark of the Alstonia macrophylla. Compounds 1-3 were unprecedented dimerization alkaloids incorporating a macroline-type motif with an ajmaline-type motif via a C-C linkage. Their structures and absolute configurations were elucidated by extensive spectroscopic analysis, electronic circular dichroism (ECD) calculation, and CD exciton chirality method. Compounds 1-3 displayed potential inhibitory bioactivity against AChE with IC50 values of 4.44 ± 0.35, 3.59 ± 0.18, and 3.71 ± 0.23 µM, respectively. Enzyme kinetic study revealed compounds 1-3 as mixed competitive AChE inhibitors. Besides, compounds 8 and 12-14 exhibited better cytotoxicity against human cancer cell line HT-29 than cisplatin. Flow cytometry data revealed that compounds 8, 13, and 14 significantly induced the HT-29 cells arrest in G0/G1 phase in a concentration-dependent manner.

Asunto(s)

Acetilcolinesterasa , Alstonia , Antineoplásicos Fitogénicos , Inhibidores de la Colinesterasa , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Alstonia/química , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/química , Inhibidores de la Colinesterasa/aislamiento & purificación , Acetilcolinesterasa/metabolismo , Estructura Molecular , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Relación Estructura-Actividad , Células HT29 , Proliferación Celular/efectos de los fármacos , Alcaloides de Triptamina Secologanina/farmacología , Alcaloides de Triptamina Secologanina/química , Alcaloides de Triptamina Secologanina/aislamiento & purificación

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BACKGROUND: Primary hepatic lymphoma (PHL) is a lymphoproliferative disorder confined to the liver without peripheral lymph node involvement and bone marrow invasion. PHL is extremely rare in clinical practice. The etiology and pathogenesis of PHL are largely unknown. There are no common standard protocols or guidelines for the treatment of PHL. CASE SUMMARY: We report the case of a 66-year-old man who presented with fever and abdominal pain for three weeks. Computed tomography and magnetic resonance imaging scans showed a pyogenic liver abscess. The patient underwent a right posterior hepatectomy. The surgical pathology revealed aggressive B-cell lymphoma, with a primary consideration of diffuse large B-cell lymphoma of non-germinal center origin. CONCLUSION: This article reviews the characteristics, mechanism and treatment of PHL and provides insight into the diagnosis of PHL.

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BACKGROUND: Liquid biopsies, for example, exosomal circular RNA (circRNA) can be used to assess potential predictive markers for hepatocellular carcinoma (HCC) in patients after curative resection. This study aimed to search for effective prognostic biomarkers for HCC in patients after surgical resection based on exosomal circRNA expression profiles. We developed two nomograms incorporating circRNAs to predict the postoperative recurrence-free survival (RFS) and overall survival (OS) of HCC patients. METHOD: Plasma exosomes isolated from HCC patients and healthy individuals were used for circRNA microarray analysis to explore differentially expressed circRNAs. Pearson correlation analysis was used to evaluate the correlation between circRNAs and clinicopathological features. Cox regression analysis was used to explore the correlation between circRNA and postoperative survival time as well as recurrence time. A nomogram based on circRNA and clinicopathological characteristics was established and further evaluated to predict prognosis and recurrence. RESULT: Among 60 significantly upregulated circRNAs and 25 downregulated circRNAs, hsa_circ_0029325 was selected to verify its power for predicting HCC outcomes. The high expression level of exosomal hsa_circ_0029325 was significantly correlated with OS (P = 0.001, HR = 2.04, 95% CI 1.41-3.32) and RFS (P = 0.009, HR = 1.62, 95% CI 1.14-2.30). Among 273 HCC patients, multivariate regression analysis showed that hsa_circ_0029325 (HR = 1.96, 95% CI 1.21-3.18), tumor size (HR = 2.11, 95% CI 1.33-3.32), clinical staging (HR = 2.31, 95% CI 1.54-3.48), and tumor thrombus (HR = 1.74, 95% CI 1.12-2.7) were independent risk factors for poor prognosis in HCC patients after radical resection. These independent predictors of prognosis were incorporated into the two nomograms. The AUCs under the 1-year, 3-year, and 5-year survival and recurrence curves of the OS and RFS nomograms were 0.755, 0.749, and 0.742 and 0.702, 0.685, and 0.642, respectively. The C-index, calibration curves, and clinical decision curves showed that the two prediction models had good predictive performance. These results were verified in the validation cohort with 90 HCC patients. CONCLUSION: Our study established two reliable nomograms for predicting recurrence and prognosis in HCC patients. We also show that it is feasible to screen potential predictive markers for HCC after curative resection through exosomal circRNA expression profile analysis.

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In the original publication [...].

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Temporomandibular disorders (TMDs) are a heterogeneous group of musculoskeletal and neuromuscular conditions involving the temporomandibular joint (TMJ), masticatory muscles, and associated structures. Mesenchymal stromal/stem cells (MSCs) have emerged as a promising therapy for TMJ repair. This systematic review aims to consolidate findings from the preclinical animal studies evaluating MSC-based therapies, including MSCs, their secretome, and extracellular vesicles (EVs), for the treatment of TMJ cartilage/osteochondral defects and osteoarthritis (OA). Following the PRISMA guidelines, PubMed, Embase, Scopus, and Cochrane Library databases were searched for relevant studies. A total of 23 studies involving 125 mice, 149 rats, 470 rabbits, and 74 goats were identified. Compliance with the ARRIVE guidelines was evaluated for quality assessment, while the SYRCLE risk of bias tool was used to assess the risk of bias for the studies. Generally, MSC-based therapies demonstrated efficacy in TMJ repair across animal models of TMJ defects and OA. In most studies, animals treated with MSCs, their derived secretome, or EVs displayed improved morphological, histological, molecular, and behavioral pain outcomes, coupled with positive effects on cellular proliferation, migration, and matrix synthesis, as well as immunomodulation. However, unclear risk in bias and incomplete reporting highlight the need for standardized outcome measurements and reporting in future investigations.

Asunto(s)

Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Trastornos de la Articulación Temporomandibular , Articulación Temporomandibular , Animales , Articulación Temporomandibular/patología , Células Madre Mesenquimatosas/citología , Trasplante de Células Madre Mesenquimatosas/métodos , Trastornos de la Articulación Temporomandibular/terapia , Humanos , Osteoartritis/terapia , Osteoartritis/patología , Vesículas Extracelulares/trasplante , Vesículas Extracelulares/metabolismo , Modelos Animales de Enfermedad

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Background: It is unclear how post-stroke cognitive trajectories differ by stroke type and ischemic stroke subtype. We studied associations between stroke types (ischemic, hemorrhagic), ischemic stroke subtypes (cardioembolic, large artery atherosclerotic, lacunar/small vessel, cryptogenic/other determined etiology), and post-stroke cognitive decline. Methods: This pooled cohort analysis from four US cohort studies (1971-2019) identified 1,143 dementia-free individuals with acute stroke during follow-up: 1,061 (92.8%) ischemic, 82 (7.2%) hemorrhagic, 49.9% female, 30.8% Black. Median age at stroke was 74.1 (IQR, 68.6, 79.3) years. Outcomes were change in global cognition (primary) and changes in executive function and memory (secondary). Outcomes were standardized as T-scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1-SD difference in cognition. Median follow-up for the primary outcome was 6.0 (IQR, 3.2, 9.2) years. Linear mixed-effects models estimated changes in cognition after stroke. Results: On average, the initial post-stroke global cognition score was 50.78 points (95% CI, 49.52, 52.03) in ischemic stroke survivors and did not differ in hemorrhagic stroke survivors (difference, -0.17 points [95% CI, -1.64, 1.30]; P=0.82) after adjusting for demographics and pre-stroke cognition. On average, ischemic stroke survivors showed declines in global cognition, executive function, and memory. Post-stroke declines in global cognition, executive function, and memory did not differ between hemorrhagic and ischemic stroke survivors. 955 ischemic strokes had subtypes: 200 (20.9%) cardioembolic, 77 (8.1%) large artery atherosclerotic, 207 (21.7%) lacunar/small vessel, 471 (49.3%) cryptogenic/other determined etiology. On average, small vessel stroke survivors showed declines in global cognition and memory, but not executive function. Initial post-stroke cognitive scores and cognitive declines did not differ between small vessel survivors and survivors of other ischemic stroke subtypes. Post-stroke vascular risk factor levels did not attenuate associations. Conclusion: Stroke survivors had cognitive decline in multiple domains. Declines did not differ by stroke type or ischemic stroke subtype.

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The advent of general anesthesia (GA) has significant implications for clinical practice. However, the exact mechanisms underlying GA-induced transitions in consciousness remain elusive. Given some similarities between GA and sleep, the sleep-arousal neural nuclei and circuits involved in sleep-arousal, including the 5-HTergic system, could be implicated in GA. Herein, we utilized pharmacology, optogenetics, chemogenetics, fiber photometry, and retrograde tracing to demonstrate that both endogenous and exogenous activation of the 5-HTergic neural circuit between the dorsal raphe nucleus (DR) and basolateral amygdala (BLA) promotes arousal and facilitates recovery of consciousness from sevoflurane anesthesia. Notably, the 5-HT1A receptor within this pathway holds a pivotal role. Our findings will be conducive to substantially expanding our comprehension of the neural circuit mechanisms underlying sevoflurane anesthesia and provide a potential target for modulating consciousness, ultimately leading to a reduction in anesthetic dose requirements and side effects.

Asunto(s)

Anestésicos por Inhalación , Complejo Nuclear Basolateral , Estado de Conciencia , Núcleo Dorsal del Rafe , Sevoflurano , Sevoflurano/farmacología , Animales , Núcleo Dorsal del Rafe/efectos de los fármacos , Núcleo Dorsal del Rafe/metabolismo , Estado de Conciencia/efectos de los fármacos , Anestésicos por Inhalación/farmacología , Complejo Nuclear Basolateral/efectos de los fármacos , Complejo Nuclear Basolateral/metabolismo , Complejo Nuclear Basolateral/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Serotonina/metabolismo , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/fisiología , Receptor de Serotonina 5-HT1A/metabolismo , Optogenética

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Ten C-geranylated flavonoids, along with three known analogues, were isolated from the leaves of Artocarpus communis. The chemical structures of these compounds were unambiguously determined via comprehensive spectroscopic analysis, single-crystal X-ray diffraction experiments, and quantum chemical electronic circular dichroism calculations. Structurally, artocarones A-I (1-9) represent a group of unusual, highly modified C-geranylated flavonoids, in which the geranyl chain is cyclised with the ortho-hydroxy group of flavonoids to form various heterocyclic scaffolds. Notably, artocarones E and G-I (5 and 7-9) feature a 6H-benzo[c]chromene core that is hitherto undescribed in C-geranylated flavonoids. Artocarone J (10) is the first example of C-9-C-16 connected C-geranylated aurone. Meanwhile, the plausible biosynthetic pathways for these rare C-geranylated flavonoids were also proposed. Notably, compounds 1, 2, 4, 8, 11, and 12 exhibited promising in vitro inhibitory activities against respiratory syncytial virus and herpes simplex virus type 1.

Asunto(s)

Antivirales , Artocarpus , Flavonoides , Flavonoides/química , Flavonoides/aislamiento & purificación , Flavonoides/farmacología , Artocarpus/química , Antivirales/química , Antivirales/farmacología , Antivirales/aislamiento & purificación , Estructura Molecular , Herpesvirus Humano 1/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Virus Sincitiales Respiratorios/efectos de los fármacos , Hojas de la Planta/química , Relación Estructura-Actividad , Modelos Moleculares

RESUMEN

BACKGROUND: Solute carrier family 34 member 2 (SLC34A2) has been implicated in the development of various malignancies. However, the clinical significance and underlying molecular mechanisms of SLC34A2 in esophageal squamous cell carcinoma (ESCC) remain elusive. METHODS: Western blotting, quantitative real-time PCR and immunohistochemistry were utilized to evaluate the expression levels of SLC34A2 mRNA/protein in ESCC cell lines or tissues. Kaplan-Meier curves were employed for survival analysis. CCK-8, colony formation, EdU and xenograft tumor model assays were conducted to determine the impact of SLC34A2 on ESCC cell proliferation. Cell cycle was examined using flow cytometry. RNA-sequencing and enrichment analysis were carried out to explore the potential signaling pathways. The autophagic flux was evaluated by western blotting, mRFP-GFP-LC3 reporter system and transmission electron microscopy. Immunoprecipitation and mass spectrometry were utilized for identification of potential SLC34A2-interacting proteins. Cycloheximide (CHX) chase and ubiquitination assays were conducted to test the protein stability. RESULTS: The expression of SLC34A2 was significantly upregulated in ESCC and correlated with unfavorable clinicopathologic characteristics particularly the Ki-67 labeling index and poor prognosis of ESCC patients. Overexpression of SLC34A2 promoted ESCC cell proliferation, while silencing SLC34A2 had the opposite effect. Moreover, SLC34A2 induced autophagy to promote ESCC cell proliferation, whereas inhibition of autophagy suppressed the proliferation of ESCC cells. Further studies showed that SLC34A2 interacted with an autophagy-related protein STX17 to promote autophagy and proliferation of ESCC cells by inhibiting the ubiquitination and degradation of STX17. CONCLUSIONS: These findings indicate that SLC34A2 may serve as a prognostic biomarker for ESCC.

Asunto(s)

Autofagia , Proliferación Celular , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Animales , Femenino , Humanos , Masculino , Ratones , Línea Celular Tumoral , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/metabolismo , Carcinoma de Células Escamosas de Esófago/genética , Cadena Pesada de la Proteína-1 Reguladora de Fusión/metabolismo , Cadena Pesada de la Proteína-1 Reguladora de Fusión/genética , Regulación Neoplásica de la Expresión Génica , Ratones Desnudos , Pronóstico , Proteínas Cotransportadoras de Sodio-Fosfato de Tipo IIb/metabolismo , Proteínas Cotransportadoras de Sodio-Fosfato de Tipo IIb/genética , Ensayos Antitumor por Modelo de Xenoinjerto

RESUMEN

PURPOSE: To summarize the clinical and biochemical characteristics of patients with ceftriaxone-induced liver injury and guide the selection of safe medication. METHODS: Retrieved domestic and foreign databases from inception to October 2023, collected case data conforming to ceftriaxone-induced liver injury, and statistically analyzed the data. RESULTS: A total of 617 articles were retrieved, and 16 articles with 33 cases (10 children, 23 adults) were included. Males represented 60% (18/30), with a male-to-female ratio of 1.5:1. The age of onset ranged from 2 days to 96 years, with 15 of 23 adults (65%) over 55 years old. The time from ceftriaxone use to liver injury fluctuated between 0.5 and 47 days. Only 9 patients (27.3%, 9/33) had clinical symptoms, and the clinical classification was dominated by cholestatic injury (46.2%, 12/26). There was a significant difference in the clinical classification of ceftriaxone-induced liver injury between children and adults (P = 0.0126), with hepatocellular injury predominating in children and cholestatic injury predominating in adults. The severity of liver injury was mainly mild (66.7%, 12/18). Peak values of alanine aminotransferase ranging from 228.5 to 8098 U/L, aspartate aminotransferase ranging from 86.7 to 21575 U/L, alkaline phosphatase ranging from 143 to 2434 U/L, and total bilirubin ranging from 3.35 to 66.1 mg/dL. There was a significant difference in peak values of alkaline phosphatase between children and adults (P = 0.027), with a higher peak value of alkaline phosphatase in adults (1039 ± 716.4 U/L vs. 257 ± 134.9 U/L). Patients with normal imaging examinations accounted for the majority (61.5%, 7/13). The prognosis of 32 patients (97%, 32/33) was good, and one child with sickle cell anemia who developed immune hemolysis, progressive renal failure, and acute liver injury after using ceftriaxone died in the end. CONCLUSION: Ceftriaxone-induced liver injury can occur at any age, with a higher risk in the elderly, and age may be related to the clinical classification. Although the clinical manifestations are not specific, close monitoring of liver biochemical indicators during the use can detect liver injury early. Most cases have a good prognosis, but for people with concomitant sickle cell anemia, it is necessary to be vigilant about the occurrence of severe hemolytic anemia.

Asunto(s)

Antibacterianos , Ceftriaxona , Enfermedad Hepática Inducida por Sustancias y Drogas , Humanos , Ceftriaxona/efectos adversos , Masculino , Femenino , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Niño , Adulto , Persona de Mediana Edad , Preescolar , Antibacterianos/efectos adversos , Adolescente , Anciano , Lactante , Adulto Joven , Anciano de 80 o más Años , Recién Nacido , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Fosfatasa Alcalina/sangre

RESUMEN

The development of sustainable flame retardants is gaining momentum due to their enhanced safety attributes and environmental compatibility. One effective strategy is to use waste materials as a primary source of chemical components, which can help mitigate environmental issues associated with traditional flame retardants. This paper reviews recent research in flame retardancy for waste flame retardants, categorizing them based on waste types like industrial, food, and plant waste. The paper focuses on recent advancements in this area, focusing on their impact on the thermal stability, flame retardancy, smoke suppression, and mechanical properties of polymeric materials. The study also provides a summary of functionalization methodologies used and key factors involved in modifying polymer systems. Finally, their major challenges and prospects for the future are identified.

RESUMEN

Our preliminary research proposed the cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and hydroxyacyl-coenzyme A dehydrogenase trifunctional multienzyme complex beta subunit (HADHB) genes as candidates for association with milk-production traits in dairy cattle because of their differential expression across different lactation stages in the liver tissues of Chinese Holstein cows and their potential roles in lipid metabolism. Hence, we identified single-nucleotide polymorphisms (SNPs) of the CYP7A1 and HADHB genes and validated their genetic effects on milk-production traits in a Chinese Holstein population with the goal of providing valuable genetic markers for genomic selection (GS) in dairy cattle, This study identified five SNPs, 14:g.24676921A>G, 14:g.24676224G>A, 14:g.24675708G>T, 14:g.24665961C>T, and 14:g.24664026A>G, in the CYP7A1 gene and three SNPs, 11:g.73256269T>C, 11:g.73256227A>C, and 11:g.73242290C>T, in HADHB. The single-SNP association analysis revealed significant associations (p value ≤ 0.0461) between the eight SNPs of CYP7A1 and HADHB genes and 305-day milk, fat and protein yields. Additionally, using Haploview 4.2, we found that the five SNPs of CYP7A1 formed two haplotype blocks and that the two SNPs of HADHB formed one haplotype block; notably, all three haplotype blocks were also significantly associated with milk, fat and protein yields (p value ≤ 0.0315). Further prediction of transcription factor binding sites (TFBSs) based on Jaspar software (version 2023) showed that the 14:g.24676921A>G, 14:g.24675708G>T, 11:g.73256269T>C, and 11:g.73256227A>C SNPs could alter the 5' terminal TFBS of the CYP7A1 and HADHB genes. The 14:g.24665961C>T SNP caused changes in the structural stability of the mRNA for the CYP7A1 gene. These alterations have the potential to influence gene expression and, consequently, the phenotype associated with milk-production traits. In summary, we have confirmed the genetic effects of CYP7A1 and HADHB genes on milk-production traits in dairy cattle and identified potential functional mutations that we suggest could be used for GS of dairy cattle and in-depth mechanistic studies of animals.

RESUMEN

Cooperative perception in the field of connected autonomous vehicles (CAVs) aims to overcome the inherent limitations of single-vehicle perception systems, including long-range occlusion, low resolution, and susceptibility to weather interference. In this regard, we propose a high-precision 3D object detection V2V cooperative perception algorithm. The algorithm utilizes a voxel grid-based statistical filter to effectively denoise point cloud data to obtain clean and reliable data. In addition, we design a feature extraction network based on the fusion of voxels and PointPillars and encode it to generate BEV features, which solves the spatial feature interaction problem lacking in the PointPillars approach and enhances the semantic information of the extracted features. A maximum pooling technique is used to reduce the dimensionality and generate pseudoimages, thereby skipping complex 3D convolutional computation. To facilitate effective feature fusion, we design a feature level-based crossvehicle feature fusion module. Experimental validation is conducted using the OPV2V dataset to assess vehicle coperception performance and compare it with existing mainstream coperception algorithms. Ablation experiments are also carried out to confirm the contributions of this approach. Experimental results show that our architecture achieves lightweighting with a higher average precision (AP) than other existing models.