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Cancer immunotherapy has transformed treatment possibilities, but its effectiveness differs significantly among patients, indicating the presence of alternative pathways for immune evasion. Here, we show that ITPRIPL1 functions as an inhibitory ligand of CD3ε, and its expression inhibits T cells in the tumor microenvironment. The binding of ITPRIPL1 extracellular domain to CD3ε on T cells significantly decreased calcium influx and ZAP70 phosphorylation, impeding initial T cell activation. Treatment with a neutralizing antibody against ITPRIPL1 restrained tumor growth and promoted T cell infiltration in mouse models across various solid tumor types. The antibody targeting canine ITPRIPL1 exhibited notable therapeutic efficacy against naturally occurring tumors in pet clinics. These findings highlight the role of ITPRIPL1 (or CD3L1, CD3ε ligand 1) in impeding T cell activation during the critical "signal one" phase. This discovery positions ITPRIPL1 as a promising therapeutic target against multiple tumor types.
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Complexo CD3 , Ativação Linfocitária , Linfócitos T , Evasão Tumoral , Microambiente Tumoral , Animais , Complexo CD3/metabolismo , Complexo CD3/imunologia , Humanos , Camundongos , Linfócitos T/imunologia , Linfócitos T/metabolismo , Microambiente Tumoral/imunologia , Cães , Neoplasias/imunologia , Linhagem Celular Tumoral , Feminino , Ligação Proteica , Proteína-Tirosina Quinase ZAP-70/metabolismo , Anticorpos Neutralizantes/imunologia , Camundongos Endogâmicos C57BLRESUMO
Protein ubiquitination is one of the most important posttranslational modifications (PTMs) in eukaryotes and is involved in the regulation of almost all cellular signaling pathways. The intracellular bacterial pathogen Legionella pneumophila translocates at least 26 effectors to hijack host ubiquitination signaling via distinct mechanisms. Among these effectors, SidC/SdcA are novel E3 ubiquitin ligases with the adoption of a Cys-His-Asp catalytic triad. SidC/SdcA are critical for the recruitment of endoplasmic reticulum (ER)-derived vesicles to the Legionella-containing vacuole (LCV). However, the ubiquitination targets of SidC/SdcA are largely unknown, which restricts our understanding of the mechanisms used by these effectors to hijack the vesicle trafficking pathway. Here, we demonstrated that multiple Rab small GTPases and target soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) proteins are bona fide ubiquitination substrates of SidC/SdcA. SidC/SdcA-mediated ubiquitination of syntaxin 3 and syntaxin 4 promotes their unconventional pairing with the vesicle-SNARE protein Sec22b, thereby contributing to the membrane fusion of ER-derived vesicles with the phagosome. In addition, our data reveal that ubiquitination of Rab7 by SidC/SdcA is critical for its association with the LCV membrane. Rab7 ubiquitination could impair its binding with the downstream effector Rab-interacting lysosomal protein (RILP), which partially explains why LCVs avoid fusion with lysosomes despite the acquisition of Rab7. Taken together, our study reveals the biological mechanisms employed by SidC/SdcA to promote the maturation of the LCVs.
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Legionella pneumophila , Fagossomos , Proteínas SNARE , Ubiquitinação , Proteínas rab de Ligação ao GTP , Legionella pneumophila/metabolismo , Humanos , Fagossomos/metabolismo , Fagossomos/microbiologia , Proteínas SNARE/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Animais , Proteínas Qa-SNARE/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Vacúolos/metabolismo , Vacúolos/microbiologia , Células HEK293 , Camundongos , proteínas de unión al GTP Rab7/metabolismo , Proteínas Monoméricas de Ligação ao GTP/metabolismo , Retículo Endoplasmático/metabolismoRESUMO
BACKGROUND: The hip joint capsule is an essential component of hip joint function and stability, and its thickness is closely associated with certain medical conditions, surgical outcomes, and rehabilitation treatments. Currently, in clinical practice, hip joint capsule thickness is predominantly measured using magnetic resonance imaging (MRI), with limited utilization of ultrasound examinations for this purpose. METHODS: We retrospectively evaluated patients who visited our Sports Medicine Department between February 2017 and March 2023 and underwent both hip joint MRI and ultrasound imaging on the same side. All patients had undergone preoperative hip joint MRI and ultrasound examinations, with the time gap between the two examinations not exceeding three months. Measurements of hip joint capsule thickness were taken on both MRI and ultrasound images for the same patients to analyze their consistency. Additionally, we measured the alpha angle, lateral center-edge angle, acetabular anteversion angle, and femoral anteversion angle of the patients' hip joints and analyzed their correlation with hip joint capsule thickness measure by ultrasound. RESULTS: A total of 307 patients were included in this study, with hip joint capsule thickness measured by MRI and ultrasound being 5.0 ± 1.2 mm and 5.0 ± 1.5 mm, respectively. The Bland-Altman analysis demonstrates good agreement or consistency. The paired t-test resulted in a p-value of 0.708, indicating no significant statistical difference between the two methods. The correlation analysis between acetabular anteversion angle and ultrasound-measured capsule thickness yielded a p-value of 0.043, indicating acetabular anteversion angle and capsular thickness may have negative correlation. CONCLUSIONS: The measurements of joint capsule thickness obtained through ultrasound and MRI showed good consistency, suggesting that ultrasound can be used in clinical practice as a replacement for MRI in measuring hip joint capsule thickness. There was a significant correlation between acetabular anteversion angle and hip joint capsule thickness, indicating potential for further research in this area.
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Acetábulo , Articulação do Quadril , Humanos , Estudos Retrospectivos , Articulação do Quadril/cirurgia , Acetábulo/cirurgia , Cápsula Articular/diagnóstico por imagem , UltrassonografiaRESUMO
BACKGROUND: Several studies report that radiomics provides additional information for predicting hematoma expansion in intracerebral hemorrhage (ICH). However, the comparison of diagnostic performance of radiomics for predicting revised hematoma expansion (RHE) remains unclear. METHODS: The cohort comprised 312 consecutive patients with ICH. A total of 1106 radiomics features from seven categories were extracted using Python software. Support vector machines achieved the best performance in both the training and validation datasets. Clinical factors models were constructed to predict RHE. Receiver operating characteristic curve analysis was used to assess the abilities of non-contrast computed tomography (NCCT) signs, radiomics features, and combined models to predict RHE. RESULTS: We finally selected the top 21 features for predicting RHE. After univariate analysis, 4 clinical factors and 5 NCCT signs were selected for inclusion in the prediction models. In the training and validation dataset, radiomics features had a higher predictive value for RHE (AUC = 0.83) than a single NCCT sign and expansion-prone hematoma. The combined prediction model including radiomics features, clinical factors, and NCCT signs achieved higher predictive performances for RHE (AUC = 0.88) than other combined models. CONCLUSIONS: NCCT radiomics features have a good degree of discrimination for predicting RHE in ICH patients. Combined prediction models that include quantitative imaging significantly improve the prediction of RHE, which may assist in the risk stratification of ICH patients for anti-expansion treatments.
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Hemorragia Cerebral , Progressão da Doença , Hematoma , Valor Preditivo dos Testes , Humanos , Masculino , Hemorragia Cerebral/diagnóstico por imagem , Hematoma/diagnóstico por imagem , Feminino , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Reprodutibilidade dos Testes , Interpretação de Imagem Radiográfica Assistida por Computador , Máquina de Vetores de Suporte , Tomografia Computadorizada por Raios X , Prognóstico , Fatores de Risco , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: This study explores the use of liquid-liquid extraction with thermosensitive polymers for producing laccase (Lac) from Pleurotus sajor-caju. This process leverages liquid waste from the citrus industry, specifically pulp wash. The research delves into extractive fermentation and thermoseparation, both processes being facilitated by a polymer exhibiting a lower critical solution temperature transition. RESULTS: Key factors considered include the choice of polymer, its concentration, pH, separation temperature, and the behavior of the polymer-rich phase post-extractive fermentation concerning the lower critical solution temperature. Notably, under conditions of 45% by weight of Pluronic L-61 and pH 5.0 at 25 °C, the Lac resulted in an enhancement in the purification factor of 28.4-fold, compared with the Lac obtained directly from the fermentation process on the eighth day. There was an 83.6% recovery of the Lac enzyme in the bottom phase of the system. Additionally, the unique properties of Pluronic L-61, which can induce phase separation and also allow for thermoseparation, led to a secondary fraction (aqueous solution) of Lac with purification factor of 2.1 ± 0.1-fold (at 32 ± 0.9 °C and 30 ± 0.3 min without stirring) from the polymeric phase (top phase). Fourier-transform infrared analysis validated the separation data, particularly highlighting the α-helix content in the amide I region (1600-1700 cm-1 ). CONCLUSION: In summary, the insights from this study pave the way for broader industrial applications of these techniques, underscoring benefits like streamlined process integration, heightened selectivity, and superior separation efficacy. © 2023 Society of Chemical Industry.
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Lacase , Pleurotus , Lacase/metabolismo , Polímeros/química , Poloxâmero , Temperatura , Fermentação , Pleurotus/metabolismoRESUMO
Sulfolenodipyrrins are employed as building blocks to concisely and efficiently construct aromatic rings (e.g., naphthoquinone, anthraquinone, fullerenes, and phthalimide) from fused dipyrrins by programmed [4 + 2]-cycloaddition reactions. Notably, alkylamino-substitution at the α-position not only enhances the reactivity of sulfolenodipyrrins but also results in the regio-selectivity of the cycloaddition reactions. Theoretical calculations in terms of frontier orbitals of dienes, energy of dienes, steric hindrance, and aromaticity have been conducted to understand the reason in depth. Additionally, the fusion of aromatic groups enables bathochromic absorption with up to â¼130 nm for the monoadducts and to â¼200 nm for the bis-adducts. The phthalimide annulation dipyrrin displays red emission, while the other mono- or bis-adducts do not, owing to the presence of typical acceptors such as quinone analogs or fullerene.
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The photothermoelectric effect, directly converting light energy into electrical energy, shows promising prospects in self-powered broad-band optical detection, which can extend to various applications, such as sensing, optoelectronic communications, and wide-temperature-range measurements. However, the low photosensitivity, narrow-band response, and rapid performance degeneration under continuous illumination restrict its broad application. Herein, we propose a simple bottom-up strategy to manipulate nanowires (NWs) into a well-defined multilayer Te-Ag2Te-Ag NW film, resulting in a high-performance photothermoelectric photodetector with a broad-band responsivity (4.1 V/W), large detectivity (944 MHz1/2 W-1), and fast response speed (0.4-0.7 s from 365 to 1200 nm). In addition, the ultrathin structure endows this device with slow and weak transverse heat conduction, enabling a stable voltage without an obvious degeneration over 1500 s. The highly anisotropic arrangement of NWs gives this device a prominent polarization sensitivity. Prospectively, this hierarchically designed nanowire film provides a promising pathway toward engineering photodetectors with high performance.
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The health risk of antibiotic-resistant genes (ARGs) has been a global concern, while the report on occurrence and prevalence of ARGs in coastal zone is relatively scarce. This study investigated typical ARGs in soil and sediment in coastal line of eastern China and assessed its relationship with antibiotics and heavy metals as well as microbial community. Results showed that eight ARGs were all detected in the samples, and ß-lactam resistance gene blaTEM reached the highest absolute abundance (6.28 × 107 ~ 6.48 × 108 copies/g) and relative abundance (2.3 × 10-2 copies/16S rRNA) among samples. Amoxicillin and tetracycline were most frequently detected with the average concentration of 2.28 µg/kg and 3.48 µg/kg, respectively. Cr and Zn were found to be most abundant heavy metals with average value of 82.1 and 59.1 mg/kg, respectively. Proteobacteria, Campilobacterota, Bacteroidota, and Firmicutes were dominant phyla in most samples, while bacterial community varied significantly among samples. Redundancy analyses (RDA) showed that microbial community and antibiotics (amoxicillin and tetracycline) were driving factors of ARGs distribution, while heavy metals were not significantly correlated with ARGs. This study is helpful to understand the fate of ARGs in coastal zone.
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Metais Pesados , Microbiota , Amoxicilina/análise , Antibacterianos/farmacologia , China , Resistência Microbiana a Medicamentos/genética , Monitoramento Ambiental , Genes Bacterianos , Metais Pesados/análise , RNA Ribossômico 16S/genética , Solo , Tetraciclina/análiseRESUMO
BACKGROUND AND AIMS: Tumor metastasis is a major factor of high recurrence and mortality in hepatocellular carcinoma (HCC), but its underlying mechanism remains elusive. We report that PDZ and LIM domain protein 1 (PDLIM1) is significantly down-regulated in metastatic human HCC tissues, which predicts unfavorable prognosis, suggesting that PDLIM1 may play an important inhibitory role during HCC metastasis. APPROACH AND RESULTS: Functional studies indicate that PDLIM1 knockdown induces epithelial-to-mesenchymal transition (EMT) of HCC cells, elevates their invasive capacity, and promotes metastasis in vitro and in vivo, whereas overexpression of PDLIM1 exhibits opposite phenotypes. Mechanistically, PDLIM1 competitively binds to the cytoskeleton cross-linking protein alpha-actinin 4 (ACTN4), leading to the disassociation of ACTN4 from F-actin, thus preventing F-actin overgrowth. In contrast, loss of PDLIM1 induces excessive F-actin formation, resulting in dephosphorylation of large tumor suppressor kinase 1 and activation of Yes-associated protein, thereby promoting HCC metastasis. Moreover, Asn145 (N145) of PDLIM1 is critical for its interaction with ACTN4, and N145A mutation abolishes its regulatory function in Hippo signaling and HCC metastasis. CONCLUSIONS: Our findings indicate that PDLIM1 suppresses HCC metastasis by modulating Hippo signaling, suggesting that PDLIM1 may be a potential prognostic marker for metastatic HCC.
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Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/secundário , Proteínas com Domínio LIM/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Fatores de Transcrição/metabolismo , Actinina/metabolismo , Actinas/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Via de Sinalização Hippo , Humanos , Proteínas com Domínio LIM/genética , Neoplasias Hepáticas/genética , Metástase Neoplásica , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Fatores de Transcrição/genética , Proteínas de Sinalização YAPRESUMO
With the rapid development of the social economy, high-voltage transmission lines as power supply infrastructure are increasing, subsequently presenting a new challenge to the effective monitoring of transmission lines. The dynamic sensor network integrated with robots can effectively solve the elastic monitoring of transmission lines, but the problems of real-time performance, energy consumption and economy of the network need to be solved. To solve this problem, a dynamic network deployment method based on the hybrid hierarchical network (HHN) is proposed to realize a low-cost, energy-saving and real-time dynamic sensing system for overhead high-voltage transmission lines. Through case analysis and simulation, combined with the vague set multi-attribute decision-making method (MADM) with scheme preference, the network deployment and optimization results under multi-parameter constraints are obtained.
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BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a common cancer worldwide and remains a major clinical challenge. Ketoconazole, a traditional antifungal agent, has attracted considerable attention as a therapeutic option for cancer treatment. However, its mechanism of action is still not clearly defined. We aimed to evaluate the effect of ketoconazole on HCC and investigate the underlying mechanisms. METHODS: We examined the antitumor effect of ketoconazole on HCC cells, cell line-derived xenografts, and a patient-derived xenograft (PDX) model. Ketoconazole-induced mitophagy was quantified by immunofluorescence, immunoblotting and transmission electron microscopy analysis. We used mitophagy inhibitors to study the role of mitophagy on HCC cell death induced by ketoconazole. The role of cyclooxygenase-2 (COX-2 [encoded by PTGS2]) on ketoconazole-induced mitophagy was evaluated using gain- and loss-of-function methods. The synergistic effect of ketoconazole with sorafenib on HCC was measured in vivo and in vitro. RESULTS: Ketoconazole stimulated apoptosis in HCC cells by triggering mitophagy in vitro and in vivo. Mechanistically, ketoconazole downregulated COX-2, which led to PINK1 accumulation and subsequent mitochondrial translocation of Parkin (PRKN), and thereby promoted mitophagy-mediated mitochondrial dysfunction. Inhibiting mitophagy alleviated ketoconazole-induced mitochondrial dysfunction and apoptosis, supporting a causal role for mitophagy in the antitumor effect of ketoconazole. In the HCC PDX model, ketoconazole demonstrated a marked antitumor effect characterized by COX-2 downregulation, mitophagy activation, and apoptosis induction. Moreover, ketoconazole acted synergistically with sorafenib to suppress HCC xenograft growth in vivo. CONCLUSION: Our results demonstrate a novel link between ketoconazole and mitophagy machinery, providing preclinical proof of concept for the use of ketoconazole in HCC treatment. LAY SUMMARY: Hepatocellular carcinoma (HCC) is a common malignancy worldwide and remains a major clinical challenge. Our study reveals that ketoconazole, a broad-spectrum antifungal agent, activates PINK1/Parkin-mediated mitophagy by downregulating COX-2, consequently resulting in the acceleration of apoptosis and thereby inhibiting the growth of HCC. Furthermore, ketoconazole acts synergistically with sorafenib in the suppression of HCC growth in vitro and in vivo.
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Carcinoma Hepatocelular/tratamento farmacológico , Ciclo-Oxigenase 2/biossíntese , Regulação para Baixo/fisiologia , Hepatócitos/patologia , Cetoconazol/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Mitofagia/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Inibidores do Citocromo P-450 CYP3A/farmacologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologiaRESUMO
The ability of surface acoustic waves to trap and manipulate micrometer-scale particles and biological cells has led to many applications involving "acoustic tweezers" in biology, chemistry, engineering, and medicine. Here, we present 3D acoustic tweezers, which use surface acoustic waves to create 3D trapping nodes for the capture and manipulation of microparticles and cells along three mutually orthogonal axes. In this method, we use standing-wave phase shifts to move particles or cells in-plane, whereas the amplitude of acoustic vibrations is used to control particle motion along an orthogonal plane. We demonstrate, through controlled experiments guided by simulations, how acoustic vibrations result in micromanipulations in a microfluidic chamber by invoking physical principles that underlie the formation and regulation of complex, volumetric trapping nodes of particles and biological cells. We further show how 3D acoustic tweezers can be used to pick up, translate, and print single cells and cell assemblies to create 2D and 3D structures in a precise, noninvasive, label-free, and contact-free manner.
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Impressão Tridimensional , Análise de Célula Única/métodos , Som , Calibragem , Sobrevivência Celular , Simulação por Computador , Células HeLa , Humanos , Microfluídica , Análise Numérica Assistida por Computador , Pinças Ópticas , VibraçãoRESUMO
The present study investigated the adsorptive and enzymatic removal of aniline blue dye (AB) from aqueous solution using waxy riceprocessing waste (RW), peanut shell (PS), microbial waste of Aspergillus niger (MW) as low cost adsorbents, and laccase (Lac) as a biocatalyst. Commercial activated carbon (AC) was also employed to compare the adsorption performance with the three adsorbents. Dye removal was examined under various parameters in batch experiments. It was found that dye removal by RW and Lac was 89â»94% noticeably better than that by MW and PS (20â»70%). In any cases, AC produced the highest dye removal among the tested materials. The kinetics, isotherms, and thermodynamics were then analyzed to elucidate the adsorption process by the four adsorbents. The pseudo-second order kinetic was superior to the pseudo first order kinetic model in describing adsorption for all adsorbents. The Langmuir model fitted the adsorption process very well, indicating monolayer coverage of dyes on a solid surface. A thermodynamic analysis of enthalpy (ΔH°), entropy (ΔS°), and Gibbs free energy (ΔG°) classified the adsorption as a nonspontaneous and endothermic process. The results reveal diverse natural materials (e.g., processing waste RW) as novel substitutes for traditional activated carbon, as well as laccase as a green catalyst for the treatment of dye wastewater.
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Compostos de Anilina/química , Poluentes Químicos da Água/química , Água/química , Adsorção , Carvão Vegetal/química , Corantes/química , Entropia , Cinética , Temperatura , TermodinâmicaRESUMO
OBJECTIVES: Information regarding Hispanics with inflammatory bowel disease (IBD) is scarce. In this study we aimed to describe a predominantly Hispanic population with IBD in a city located along the US-Mexico border and to identify clinical or demographic differences between Hispanics and non-Hispanics. METHODS: Retrospective cohort analysis of patients with IBD between 2003 and 2013 at a tertiary care center. Information collected included age, sex, ethnicity, diagnosis, diagnosis status (new vs old), endoscopic extent of disease (EOD), extraintestinal manifestations, medical treatment, and surgeries performed. Continuous and categorical variables were compared using a two-sided unpaired t test/Wilcoxon rank sum test and the Fisher exact test, respectively. Results with P ≤ 5% were considered statistically significant. RESULTS: Hispanics accounted for 71% of the population sample. A total of 141 patients (68%) were diagnosed as having ulcerative colitis (UC) and 67 (32%) as having Crohn disease (CD). The only statistically significant differences between Hispanics and non-Hispanics were older age at diagnosis and a higher proportion of new diagnoses in Hispanics with CD (P = 0.008 and 0.009, respectively) The most common EOD in patients with UC was extensive colitis, whereas isolated colonic disease predominated in CD, regardless of ethnicity. Immunomodulators and biologics were used in 3% and 1% of cases, respectively. Treatment regimens were similar in both ethnic groups. Patients with CD were more likely than those with UC to have undergone surgery (27% vs 11%, P = 0.004). Surgery rates did not differ between Hispanics and non-Hispanics. CONCLUSIONS: In our population, UC was more common than CD, and the EOD of both conditions differed from the one previously described in other Hispanic populations in the United States. The use of immunomodulators and biologics is the lowest reported to date in the country. No clinically relevant differences were seen between Hispanics and non-Hispanics.
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Colite Ulcerativa/patologia , Doença de Crohn/patologia , Hispânico ou Latino/estatística & dados numéricos , Adulto , Fatores Etários , Produtos Biológicos/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/etnologia , Colonoscopia/estatística & dados numéricos , Doença de Crohn/tratamento farmacológico , Doença de Crohn/etnologia , Demografia , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Masculino , México/etnologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Estatísticas não Paramétricas , Estados UnidosRESUMO
Two CHI genes from Chitinolyticbacter meiyuanensis SYBC-H1 encoding chitinases were identified and their protein 3D structures were predicted. According to the amino acid sequence alignment, CHI1 gene encoding 166 aa had a structural domain similar to the GH18 type II chitinase, and CHI2 gene encoding 383 aa had the same catalytic domain as the glycoside hydrolase family 19 chitinase. In this study, CHI2 chitinase were expressed in Escherichia coli BL21 cells, and this protein was purified by ammonium sulfate precipitation, DEAE-cellulose, and Sephadex G-100 chromatography. Optimal activity of CHI2 chitinase occurred at a temperature of 40 °C and a pH of 6.5. The presence of metal ions Fe(3+), Fe(2+), and Zn(2+) inhibited CHI2 chitinase activity, while Na⺠and K⺠promoted its activity. Furthermore, the presence of EGTA, EDTA, and ß-mercaptoethanol significantly increased the stability of CHI2 chitinase. The CHI2 chitinase was active with p-NP-GlcNAc, with the Km and Vm values of 23.0 µmol/L and 9.1 mM/min at a temperature of 37 °C, respectively. Additionally, the CHI2 chitinase was characterized as an N-acetyl glucosaminidase based on the hydrolysate from chitin. Overall, our results demonstrated CHI2 chitinase with remarkable biochemical properties is suitable for bioconversion of chitin waste.
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Quitinases/química , Quitinases/genética , Clonagem Molecular/métodos , Neisseriaceae/isolamento & purificação , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Quitinases/metabolismo , Escherichia coli/genética , Cinética , Modelos Moleculares , Neisseriaceae/química , Neisseriaceae/enzimologia , Neisseriaceae/genética , Filogenia , Estabilidade Proteica , Estrutura Secundária de Proteína , Análise de Sequência de Proteína , Microbiologia do Solo , Homologia Estrutural de ProteínaRESUMO
BACKGROUND: This study examines factors related to general health and health behavior, including smoking, that may be associated with binge drinking, drinking "at risk," and potential for alcohol use disorder among young adults of Mexican ancestry. METHODS: A total of 2191 young adult emergency department (ED) patients (18-30 years) of Mexican ancestry in a public hospital proximate to the US-Mexico border completed health surveys while they were waiting to be treated, including questions on general health, drinking, smoking, and drug use. RESULTS: Thirty-seven percent of the study participants reported binge drinking, 38% were "at-risk" alcohol users (above National Institute on Alcohol Abuse and Alcoholism guidelines), and 22% were Rapid Alcohol Problem Screen (RAPS) positive (indicating potential for alcohol use disorder). Smoking was reported by 31%, marijuana use by 16%, and other drug use by 9%. Multiple variable models revealed that smoking was the strongest factor associated with binge drinking. Those who smoked were 3.1 (P < .0001) times more likely to binge drink. Other factors independently associated with binge drinking were age 22-25 years (odds ratio [OR] = 1.5, P = .003), male gender (OR = 1.5, P = .0001), and ED visit for injury (OR = 1.4, P = .007). CONCLUSIONS: There is a strong association of smoking and binge drinking. Study findings suggest that brief interventions designed to reduce preventable health risks for young Hispanics should include discussion of both binge drinking and smoking behaviors.
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Consumo Excessivo de Bebidas Alcoólicas/epidemiologia , Fumar Maconha/epidemiologia , Americanos Mexicanos/psicologia , Fumar/epidemiologia , Adolescente , Comportamento do Adolescente , Adulto , Fatores Etários , Feminino , Humanos , Masculino , México/etnologia , Fatores de Risco , Fatores Sexuais , Texas/epidemiologia , Adulto JovemRESUMO
Effective combined antiretroviral therapy (cART) in HIV-infected patients has made HIV a treatable infection; however, debilitating HIV-associated neurocognitive disorders (HAND) can still affect approximately 50% of HIV-infected individuals even under cART. While cART has greatly reduced the prevalence of the most severe form of HAND, milder forms have increased in prevalence, leaving the total proportion of HIV-infected individuals suffering from HAND relatively unchanged. In this study, an in vitro drug screen identified fluconazole and paroxetine as protective compounds against HIV gp120 and Tat neurotoxicity. Using an accelerated, consistent SIV/macaque model of HIV-associated CNS disease, we tested the in vivo neuroprotective capabilities of combination fluconazole/paroxetine (FluPar) treatment. FluPar treatment protected macaques from SIV-induced neurodegeneration, as measured by neurofilament light chain in the CSF, APP accumulation in axons, and CaMKIIα in the frontal cortex, but did not significantly reduce markers of neuroinflammation or plasma or CNS viral loads. Since HIV and SIV neurodegeneration is often attributed to accompanying neuroinflammation, this study provides proof of concept that neuroprotection can be achieved even in the face of ongoing neuroinflammation and viral replication.
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Fluconazol/farmacologia , Neurônios/efeitos dos fármacos , Nootrópicos/farmacologia , Paroxetina/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Síndrome de Imunodeficiência Adquirida dos Símios/tratamento farmacológico , Complexo AIDS Demência/tratamento farmacológico , Complexo AIDS Demência/fisiopatologia , Complexo AIDS Demência/virologia , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/fisiopatologia , Síndrome da Imunodeficiência Adquirida/virologia , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Modelos Animais de Doenças , Expressão Gênica/efeitos dos fármacos , Humanos , Macaca nemestrina , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Proteínas de Neurofilamentos/genética , Neurônios/patologia , Neurônios/virologia , Cultura Primária de Células , Ratos , Síndrome de Imunodeficiência Adquirida dos Símios/líquido cefalorraquidiano , Síndrome de Imunodeficiência Adquirida dos Símios/fisiopatologia , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/efeitos dos fármacos , Vírus da Imunodeficiência Símia/fisiologia , Carga Viral/efeitos dos fármacos , Replicação Viral/efeitos dos fármacosRESUMO
The present study focused on laccase production, characterization, and its involvement in chlorophyll decolorization. Extracellular laccase, with the highest activity of 11 U/ml on day 8, was efficiently produced from Trametes hirsuta in 5 l bioreactor with optimized media comprising dual carbon sources, glucose and water hyacinth. A laccase was then purified from the supernatant to homogeneity with purification fold of 9.51 and recovery of 39.8% and an estimated molecular mass of 62 kDa by SDS-PAGE. The laccase showed activity at pH 2-6 and temperature 30-80°C and was relatively thermally stable at below 70°C and neutral pH. The laccase was applied to decolorize chlorophyll under different factors: temperature, pH, mediator, metal ions, and enzyme dosage. Other fungal laccases were also found to be able to degrade chlorophyll with rating from 52% to 88% following 1 h treatment with two laccase dosages (5 or 10 U/ml) in the absence of any other mediators at room temperature. These findings may be an important step in developing new, important, and commercially viable industrial applications for laccase enzymes.
Assuntos
Clorofila/metabolismo , Regulação Enzimológica da Expressão Gênica/fisiologia , Regulação Fúngica da Expressão Gênica/fisiologia , Lacase/metabolismo , Trametes/enzimologia , Clorofila/química , Eletroforese em Gel de Poliacrilamida , Concentração de Íons de Hidrogênio , Lacase/genética , Estrutura Molecular , Trametes/genética , Trametes/metabolismoRESUMO
In network systems, control using minimum nodes or pinning control can be effectively used for stabilization problems to cut down the cost of control. In this paper, we investigate the set stabilization problem of logical control networks. In particular, we study the set stabilization problem of probabilistic Boolean networks (PBNs) and probabilistic Boolean control networks (PBCNs) via controlling minimal nodes. Firstly, an algorithm is given to search for the minimum index set of pinning nodes. Then, based on the analysis of its high computational complexity, we present optimized algorithms with lower computational complexity to ascertain the network control using minimum node sets. Moreover, some sufficient and necessary conditions are proposed to ensure the feasibility and effectiveness of the proposed algorithms. Furthermore, a theorem is presented for PBCNs to devise all state-feedback controllers corresponding to the set of pinning nodes. Finally, two models of gene regulatory networks are considered to show the efficacy of obtained results.
Assuntos
Algoritmos , Redes Reguladoras de GenesRESUMO
Background: Several variables may affect the traction force during hip arthroscopy. Specifically, the degree of hip joint rotation may influence the magnitude of traction force during hip arthroscopy. However, there is currently limited research available on this particular issue. Purpose: To quantify the traction force applied to the pulled limb in various traction states and rotational positions. Additionally, the study aimed to investigate potential correlations between femoral anteversion, BMI, anesthesia methods, and the traction force required for hip dislocation. Hypothesis: It was hypothesized that traction force in different traction states and rotational positions would be different and that femoral anteversion, body mass index (BMI), and anesthesia methods may influence the traction force needed. Study Design: Cross-sectional study; Level of evidence, 4. Methods: Patients who attended the sports medicine clinic of our department and underwent arthroscopic surgery for the diagnosis of femoroacetabular impingement between June and December 2022 were retrospectively evaluated. The traction force at the following 6 key timepoints was measured-initial traction, traction to the operable width, after joint puncture, after capsulotomy, at 20 minutes after capsulotomy, and at 40 minutes after capsulotomy. In each state, the hip was rotated to the internal rotational position, external rotational position, and neutral position. The traction force at different states and positions was recorded and analyzed. The differences in traction force between the different joint capsular physical states and rotational positions were tested by analysis of variance and the Tukey method. The Pearson test was used to analyze the correlation between BMI and femoral anteversion in different groups. Results: A total of 41 patients were included in this study. The traction force increased after reaching the operable width and decreased significantly after capsulotomy (P < .05). Thereafter, the traction force decreased gradually over time (P < .05). Traction force in the external and internal rotational positions was significantly greater than that in the neutral position, across all states of traction (P < .05). Furthermore, the difference in traction force between the internal and neutral positions, as well as the difference in traction force between the external and neutral positions, was found to be significantly greater than the difference in traction force between the internal and external rotational positions in all traction states (P < .05). The difference between the traction forces in different rotational positions of the hip joint exhibited a negative correlation with femoral anteversion (Pearson correlation coefficient of neutral-internal in states 3, 4, and 5 was -0.33, -0.31, -0.31, respectively; P < .05) and a positive correlation with BMI (Pearson correlation coefficient of external-neutral in states 4 and 6 was 0.33 and 0.36, respectively; P < .05). Conclusion: Our findings show that the traction force decreased after joint puncture and capsulotomy and decreased over time during surgery. External or internal rotation increased the traction force. Patients with higher femoral anteversion or lower BMI may need lower traction force. These data may help in minimizing traction forces to help prevent complications due to traction during hip arthroscopy.