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Frequent herbicide use selects for herbicide resistance in weeds. Cytochrome P450s are important detoxification enzymes responsible for herbicide resistance in plants. We identified and characterized a candidate P450 gene (BsCYP81Q32) from the problematic weed Beckmannia syzigachne to test whether it conferred metabolic resistance to the acetolactate synthase-inhibiting herbicides mesosulfuron-methyl, bispyribac-sodium, and pyriminobac-methyl. Transgenic rice overexpressing BsCYP81Q32 was resistant to the three herbicides. Equally, rice overexpressing the rice ortholog gene OsCYP81Q32 was more resistant to mesosulfuron-methyl. Conversely, an OsCYP81Q32 gene knockout generated using CRISPR/Cas9 enhanced mesosulfuron-methyl sensitivity in rice. Overexpression of the BsCYP81Q32 gene resulted in enhanced mesosulfuron-methyl metabolism in transgenic rice seedlings via O-demethylation. The major metabolite, demethylated mesosulfuron-methyl, was chemically synthesized and displayed reduced herbicidal effect in plants. Moreover, a transcription factor (BsTGAL6) was identified and shown to bind a key region in the BsCYP81Q32 promoter for gene activation. Inhibition of BsTGAL6 expression by salicylic acid treatment in B. syzigachne plants reduced BsCYP81Q32 expression and consequently changed the whole plant response to mesosulfuron-methyl. Sequence polymorphisms in an important region of the BsTGAL6 promoter may explain the higher expression of BsTGAL6 in resistant versus susceptible B. syzigachne plants. Collectively, the present study reveals the evolution of an herbicide-metabolizing and resistance-endowing P450 and its transcription regulation in an economically important weedy plant species.
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Acetolactato Sintasa , Herbicidas , Oryza , Acetolactato Sintasa/genética , Poaceae/genética , Compuestos de Sulfonilurea/farmacología , Oryza/genética , Oryza/metabolismo , Sistema Enzimático del Citocromo P-450/genética , Sistema Enzimático del Citocromo P-450/metabolismo , Herbicidas/farmacología , Resistencia a los Herbicidas/genéticaRESUMEN
BACKGROUND: In recent years, breast cancer (BC) incidence and mortality have been the highest in females. Menopause-like syndrome (MLS), arising from hypoestrogenism caused by endocrine therapy, significantly affects the quality of life for females. Traditional Chinese Medicine (TCM) has advantages in ameliorating MLS, but the efficacy of TCM in patients with BC has not been systematically evaluated. METHODS: A comprehensive search was performed on PubMed, Web of Science, Embase, Ovid, Cochrane Library, China National Knowledge Infrastructure, Wanfang database, Chinese Scientific Journals Database, and Clinical Trial Registry from inception to September 4, 2023. The Cochrane Risk of Bias assessment tool was used for the quality evaluation of the randomized controlled trials (RCTs). Review Manager 5.4 software was used for statistical analysis, and the Grading of Recommendations Assessment, Development, and Evaluation was used for quality evaluation of the synthesized evidence. RESULTS: This review included 42 studies involving 3112 female patients with BC. The results showed that the TCM group was better at decreasing the Kupperman Menopausal Index (KMI) scores (standardized MD, SMD = - 1.84, 95% confidence interval, CI [- 2.21--1.46], Z = 9.63, P < 0.00001). Regarding the main symptoms of MLS, the TCM groups could significantly decrease the scores of hot flashes and night sweats (SMD = - 0.68, 95% CI [- 1.1--0.27], Z = 3.24, P = 0.001), paraesthesia (SMD = - 0.48, 95% CI [- 0.74--0.21], Z = 3.53, P = 0.0004), osteoarthralgia (SMD = - 0.41, 95% CI [- 0.6-0.21], Z = 4.09, P < 0.0001), anxiety (MD = - 0.85, 95% CI [- 1.13, - 0.58], Z = 6.08, P < 0.00001) and insomnia (MD = - 0.61, 95% CI [- 0.8, - 0.43], Z = 6.51, P < 0.00001). TCM can effectively improve the symptoms of MLS in patients with BC. Moreover, TCM could improve the objective response rate (ORR) by 50% (RR = 1.5, 95% CI [1.37-1.64], Z = 9.01, P < 0.00001). Follicle-stimulating hormone (FSH) and oestradiol (E2) had no significant difference compared with the control group (p = 0.81 and p = 0.87), and luteinizing hormone (LH) in the TCM group decreased significantly (MD = - 0.99, 95% CI [- 1.38, - 0.5], Z = 5.01, P < 0.00001). This means that the use of TCM does not negatively affect endocrine therapy and may even have a synergistic effect. The incidence of adverse events (AEs) was lower in the TCM groups than in the control groups. CONCLUSIONS: The meta-analysis stated that TCM could better improve the MLS of patients, alleviate related symptoms, and did not increase adverse drug reactions in BC survivors. This review brings more attention to MLS, and the present findings shed light on the potential applications of TCM in the treatment of MLS in BC survivors.
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Neoplasias de la Mama , Supervivientes de Cáncer , Medicina Tradicional China , Menopausia , Femenino , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Medicina Tradicional China/efectos adversos , Menopausia/efectos de los fármacos , SíndromeRESUMEN
Marine microalgae serve as an aquaculture bait. To enhance algal cell growth and breeding profits, high-intensity light conditions are standard for cultivating bait microalgae, potentially altering microalgal metabolite production. This research revealed that Thalassiosira pseudonana, when subjected to high-intensity light conditions, accumulated significant quantities of retinal (RAL) that transferred through the food chain and transformed into all-trans retinoic acid (atRA) in marine medaka. The study further explored the toxic effects on individual fish and specific tissues, as well as the mechanisms behind this toxicity. The accumulation of atRA in the liver, intestine, and spinal column resulted in structural damage and tissue inflammation, as well as oxidative stress. It also down-regulated the gene transcription levels of key pathways involved in immune function and growth. Furthermore, it disrupted the homeostasis of the intestinal microbial communities. The implications for wildlife and human health, which are influenced by the regulation of microalgal metabolite accumulation and their transfer via the food chain, require further investigation and could hold broader significance.
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Cadena Alimentaria , Hígado , Oryzias , Animales , Oryzias/metabolismo , Hígado/metabolismo , Retinoides/metabolismo , Intestinos , Microalgas , AcuiculturaRESUMEN
Per- and polyfluoroalkyl substances (PFAS) pose significant environmental and human health risks and thus require solutions for their removal and destruction. However, PFAS cannot be destroyed by widely used removal processes like nanofiltration (NF). A few scarcely implemented advanced oxidation processes can degrade PFAS. In this study, we apply an electric field to a membrane system by placing a nanofiltration membrane between reactive electrodes in a crossflow configuration. The performance of perfluorooctanoic acid (PFOA) rejection, water flux, and energy consumption were evaluated. The reactive and robust SnO2-Sb porous anode was created via a sintering and sol-gel process. The characterization and analysis techniques included field emission scanning electron microscopy (FE-SEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), ion chromatography, mass spectroscopy, porosimeter, and pH meter. The PFOA rejection increased from 45% (0 V) to 97% (30 V) when the electric field and filtration were in the same direction, while rejection capabilities worsened in opposite directions. With saline solutions (1 mM Na2SO4) present, the induced electro-oxidation process could effectively mineralize PFOA, although this led to unstable removal and water fluxes. The design achieved an exceptional performance in the nonsaline feed of 97% PFOA rejection and water flux of 68.4 L/m2 hr while requiring only 7.31 × 10-5 kWh/m3/order of electrical energy. The approach's success is attributed to the proximity of the electrodes and membrane, which causes a stronger electric field, weakened concentration polarization, and reduced mass transfer distances of PFOA near the membrane. The proposed electric field-assisted nanofiltration design provides a practical membrane separation method for PFAS removal from water.
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Fluorocarburos , Contaminantes Químicos del Agua , Humanos , Agua , Caprilatos/química , Electricidad , Contaminantes Químicos del Agua/químicaRESUMEN
PURPOSE: The purpose of this study is to determine the incidence and severity of symptoms of patients with cervical cancer within 6 months after radiotherapy and chemotherapy, form a symptom burden report, evaluate the distribution characteristics of symptoms, identify symptom clusters, and provide a basis for clinical doctors and nurses to improve the symptom management of patients with cervical cancer after radiotherapy and chemotherapy. METHODS: The patients with cervical cancer within 6 months after radiotherapy and chemotherapy were recruited to investigate their symptom burden. Exploratory factor analysis was used to identify symptom clusters. RESULTS: A total of 250 patients participated in the study. The study found that the most common symptom among the 40 symptoms was fatigue, and the most serious symptom was nocturia. Based on the occurrence rate and severity of symptoms, nine symptom clusters were identified, including psycho-emotion-related symptom cluster, pain-disturbed sleep-related symptom cluster, menopausal symptom cluster, tinnitus-dizziness-related symptom cluster, urinary-related symptom cluster, dry mouth-bitter taste-related symptom cluster, intestinal-related symptom cluster, memory loss-numbness-related symptom cluster, and emaciation-related symptom cluster. The three most serious symptom clusters are pain-disturbed sleep-related symptom cluster, urinary-related symptom cluster, and memory loss-numbness-related symptom cluster. CONCLUSION: The symptoms of patients with cervical cancer within 6 months after radiotherapy and chemotherapy are complex, and nine symptom clusters can be identified according to the incidence and severity of symptoms. We can find the potential biological mechanism of each symptom cluster through the discussion of previous mechanism research and clinical research. The number of symptom clusters and the number of symptoms within the symptom cluster are closely related to the symptom evaluation scale selected for the study. Therefore, the symptom cluster study urgently needs a targeted symptom evaluation scale that can comprehensively reflect the patient's condition.
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Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/terapia , Estudios Transversales , Síndrome , Hipoestesia , Dolor/complicaciones , Trastornos de la Memoria , Análisis por Conglomerados , Fatiga/epidemiología , Fatiga/etiologíaRESUMEN
BACKGROUND: Maternal folate may not reach an optimal level to prevent neural tube defects if supplementation commenced post-conception or took place pre-conception only. Our study aimed to investigate the continuation of folic acid (FA) supplementation from pre-conception to post-conception during peri-conceptional period and to examine its differences in FA supplementation between the subgroups taking the initiation timing into consideration. METHODS: This study was conducted in two community health service centers in Jing-an District of Shanghai. Women accompanying their children to pediatric health clinics of the centers were recruited and asked to recall information concerning their socioeconomic and previous obstetric characteristics, utilization of healthcare and FA supplementation before and/or during pregnancy. The continuation of FA supplementation during peri-conceptional period were categorized into three subgroups: Supplementing with FA pre- and post-conception; supplementing with FA preconception only or post-conception only; no FA supplements pre-conception and post-conception. The relationship between FA continuation and couples' characteristics were examined as setting the first subgroup as the base reference. RESULTS: Three hundred and ninety-six women were recruited. Over 40% of the women started FA supplementation after conception and 30.3% of them supplemented with FA from pre-conception to the first trimester of their pregnancy. Compared to this one-third of participants, women who didn't supplemented with any FA during peri-conceptional period were more likely to have no utilization of pre-conception healthcare ([Formula: see text]= 2.47, 95% [Formula: see text]: 1.33-4.61) or antenatal care ([Formula: see text]= 4.05, 95% [Formula: see text]: 1.76-9.34), or who had a lower family socioeconomic status ([Formula: see text]= 4.36, 95% [Formula: see text]: 1.79-10.64). Women who supplemented with FA pre-conception only or post-conception only were more likely to have no utilization of pre-conception healthcare ([Formula: see text]= 2.94, 95% [Formula: see text]: 1.79-4.82), or to have no previous pregnancy complication ([Formula: see text]=1.80, 95% [Formula: see text]: 0.99-3.28). CONCLUSION: Over two-fifth of the women started FA supplementation and only one-third of them had an optimal supplementation from pre-conception to the first trimester. Maternal utilization of healthcare before or during pregnancy together with maternal and paternal socioeconomic status may play a role in the continuation to FA supplementation pre- and post-conception.
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Suplementos Dietéticos , Ácido Fólico , Niño , Femenino , Embarazo , Humanos , Estudios Transversales , China , Ácido Fólico/uso terapéutico , Atención Prenatal , Atención PreconceptivaRESUMEN
BACKGROUND: Gender nonconformity (GNC) (i.e., gender expression that differs from gender role expectations for feminine or masculine appearance and behavior) is an under-researched area of adolescent sleep health. The COVID-19 lockdown offers an opportunity to understand how the effect of GNC on adolescent health outcomes changes between school closure and reopening. METHODS: We conducted a cross-sectional study in Shanghai, China, in 2020. The sample size for analysis was 3,265. The age-specific insufficient sleep was estimated according to National Sleep Foundation's sleep duration recommendations. The self-perceived and self-rated GNC were measured by the two items "On the same scale that goes from 100% as a girl to 100% as a boy, where do you think others see you?" and "On a scale that goes from feeling 100% like a girl to feeling 100% like a boy, where do you see yourself?", and birth sex. In addition, we calculated sex-stratified adjusted odds ratios (AORs) of insufficient sleep for students with high and moderate GNC compared to students with low GNC. Finally, we measured the AORs with self-perceived and self-rated GNC during COVID-19 school closure and reopening. RESULTS: Among 3,265 students in grade 6-12 in the analytic sample, 1,567(48.0%) were assigned female at birth (AFAB), 3,188 (97.6%) Han, and 1,921(58.8%) in grade 6-9. Among AFAB students, high self-perceived GNC was significantly associated with insufficient sleep (AOR,1.65; 95%CI,1.30-2.09) during school closure. Insufficient sleep was associated with high self-rated GNC (AOR,1.73; 95%CI,1.23-2.44) and moderate self-rated GNC (AOR,1.69; 95%CI,1.29-2.22) during school closure. After school reopening, neither self-perceived nor self-rated GNC was associated with insufficient sleep among AFAB students. Among assigned male at birth (AMAB) students, none of the two kinds of GNC was associated with insufficient sleep in the two periods during the COVID-19 pandemic. CONCLUSIONS: This study suggests GNC is only associated with insufficient sleep among AFAB students during school closure. Furthermore, the association is nonsignificant among AMAB students. These findings indicate that GNC-related stigma within the family could be a risk factor for insufficient sleep among AFAB adolescents.
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COVID-19 , Privación de Sueño , Recién Nacido , Adolescente , Masculino , Humanos , Femenino , COVID-19/epidemiología , Estudios Transversales , Pandemias , China/epidemiología , Control de Enfermedades Transmisibles , Instituciones Académicas , SueñoRESUMEN
Introduction: Bromus japonicus is one of the most notorious agricultural weeds in China. The long-term use of ALS-inhibiting herbicides has led to rapid evolution of herbicide resistance in B. japonicus. B. japonicus population (BJ-R) surviving mesosulfuron-methyl treatment was collected from wheatland. Here, we aimed to confirm the resistance mechanisms in this putative resistant population. Methods: The dose-reponse tests were used to test the resistance level of the B. japonicus to ALS-inhibiting herbicides. Pretreatment with P450 and GST inhibitors and GST activity assays were used to determine whether P450 or GST was involved in the resistance of the BJ-R population. Sanger sequencing was used to analyse the ALS mutation of the BJ-R population. RT-qPCR was used to confirm the the expression levels of the ALS gene in mesosulfuron-methyl -resistant (BJ-R) and-susceptible (BJ-S) B. japonicus. An in vitro ALS activity assay was used to determine the ALS activity of the BJ-R and BJ-S populations. Homology modelling and docking were used to determine the binding energy of the BJ-R and BJ-S populations with ALS-inhibiting herbicides. Results: B. japonicus population (BJ-R) was confirmed to be 454- and 2.7-fold resistant to the SU herbicides mesosulfuron-methyl and nicosulfuron, and 7.3-, 2.3-, 1.1- and 10.8-fold resistant to the IMI herbicide imazamox, the TP herbicide penoxsulam, the PTB herbicide pyribenzoxim and the SCT herbicide flucarbazone-sodium, respectively, compared with its susceptible counterpart (BJ-S). Neither a P450 inhibitor nor a GST inhibitor could reverse the level of resistance to mesosulfuron-methyl in BJ-R. In addition, no significant differences in GST activity were found between the BJ-R and BJ-S. ALS gene sequencing revealed a Pro-197-Thr mutation in BJ-R, and the gene expression had no significant differences between the BJ-R and BJ-S. The ALS activity of BJ-R was 106-fold more tolerant to mesosulfuron-methyl than that of BJ-S. Molecular docking showed that the binding energy of the ALS active site and mesosulfuron-methyl was changed from -6.67 to -4.57 kcal mol-1 due to the mutation at position 197. Discussion: These results suggested that the Pro-197-Thr mutation was the main reason for the high resistance level of BJ-R to mesosulfuron-methyl. Unlike previous reports of the cross-resistance pattern conferred by this mutation, we firstly documented that the Pro-197-Thr mutation confers broad cross-resistance spectrums to ALS-inhibiting herbicides in B. japonicus.
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[This corrects the article DOI: 10.3389/fimmu.2023.1113303.].
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The emergence of 4-hydroxyphenylpyruvate dioxygenase (HPPD) herbicides as efficacious target-site herbicides has been noteworthy. In recent years, only four species of broadleaf weeds have developed resistance due to the long-term widespread use of HPPD herbicides. This study represents the first reported instance of a grass weed exhibiting resistance to HPPD inhibitors. We identified a new HPPD-resistant Chinese sprangletop [Leptochloa chinensis (L.) Nees] population (R population). At the recommended dose of tripyrasulfone, the inhibition rate of the R population was only half that of the sensitive population (S). The mechanism underlying resistance does not involve target-site resistance triggered by amino acid mutations or depend on disparities within the HPPD INHIBITOR SENSITIVE 1 (HIS1) gene. The impetus for resistance appears to be interlinked with the metabolic activities of cytochrome P450 monooxygenase (P450) and glutathione S-transferase (GST) family genes. Following RNA sequencing (RNA-seq) and quantitative real-time PCR (qRT-PCR) validation, the study suggests that five P450 genes, CYP71C1, CYP74A2, CYP72A1, CYP84A1, and CYP714C2, alongside a single GST gene GSTF1, may be implicated in the process of metabolic detoxification.
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4-Hidroxifenilpiruvato Dioxigenasa , Dioxigenasas , Herbicidas , Herbicidas/farmacología , Poaceae/genética , Poaceae/metabolismo , Resistencia a los Herbicidas/genética , 4-Hidroxifenilpiruvato Dioxigenasa/genética , 4-Hidroxifenilpiruvato Dioxigenasa/metabolismoRESUMEN
Bispecific antibodies have attracted more attention in recent years for the treatment of tumors, in which most of them target CD3, which mediates the killing of tumor cells by T cells. However, T-cell engager may cause serious side effects, including neurotoxicity and cytokine release syndrome. More safe treatments are still needed to address unmet medical needs, and NK cell-based immunotherapy is a safer and more effective way to treat tumors. Our study developed two IgG-like bispecific antibodies with the same configuration: BT1 (BCMA×CD3) attracted T cells and tumor cells, while BK1 (BCMA×CD16) attracted NK cells and tumor cells. Our study showed that BK1 mediated NK cell activation and upregulated the expression of CD69, CD107a, IFN-γ and TNF. In addition, BK1 elicited a stronger antitumor effect than BT1 both in vitro and in vivo. Combinatorial treatment (BK1+BT1) showed a stronger antitumor effect than either treatment alone, as indicated by in vitro experiments and in vivo murine models. More importantly, BK1 induced fewer proinflammatory cytokines than BT1 both in vitro and in vivo. Surprisingly, BK1 reduced cytokine production in the combinatorial treatment, suggesting the indispensable role of NK cells in the control of cytokine secretion by T cells. In conclusion, our study compared NK-cell engagers and T-cell engagers targeting BCMA. The results indicated that NK-cell engagers were more effective with less proinflammatory cytokine production. Furthermore, the use of NK-cell engagers in combinatorial treatment helped to reduce cytokine secretion by T cells, suggesting a bright future for NK-cell engagers in clinical settings.
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Anticuerpos Biespecíficos , Neoplasias , Ratones , Animales , Linfocitos T , Citocinas/metabolismo , Anticuerpos Biespecíficos/farmacología , Anticuerpos Biespecíficos/uso terapéutico , Antígeno de Maduración de Linfocitos B/metabolismo , Células Asesinas NaturalesRESUMEN
Butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) are two important cholinesterase enzymes in human metabolism which are closely related to various diseases of the liver. BChE and AChE are difficult to be distinguished due to their similarity in biochemical properties. Therefore, developing BChE-specific probes with high sensitivity and low background reading is desirable for the relevant biological applications. Herein, we reported the design and synthesis of a fluorescent probe HBT-BChE for biological detection and imaging of BChE. The probe is triggered by BChE-mediated hydrolysis, releasing a fluorophore that holds AIEE and ESIPT properties with large Stokes shift (>100 nm), rendering the probe features of low background interference and high sensitivity. The probe can also distinguish BChE from AChE with a low detection limit of 7.540 × 10-4 U/mL. Further in vitro studies have shown the ability of HBT-BChE to detect intracellular BChE activity, as well as to evaluate the efficiency of the BChE inhibitor. More importantly, the in vivo studies of imaging the BChE activity level in liver tissues using zebrafish as the model animal demonstrated the potential of HBT-BChE as a powerful tool for non-alcoholic fatty liver disease.
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Butirilcolinesterasa , Enfermedad del Hígado Graso no Alcohólico , Animales , Humanos , Butirilcolinesterasa/metabolismo , Acetilcolinesterasa/metabolismo , Pez Cebra/metabolismo , Colorantes Fluorescentes/químicaRESUMEN
Individuals' gender development is influenced by the characteristics of personal and contextual environments. However, the role of sibling contexts in shaping gender norms has rarely been studied among Chinese youth at early adolescence as most of them were the only child. The aim of this paper is to compare perceived gender norms among adolescents aged 10-14 with different sibling configurations, to help inform and tailor guidance for sexual and reproductive health education in the future. We used the Global Early Adolescent Study baseline data collected from Shanghai, China. The sample for analysis was 1615 students. We used univariate analysis and multivariate ordinal logistic regression to compare perceived gender-stereotyped traits and gender role attitudes, stratified by age and sex. The results showed that sibling context was more influential for boys than girls at early adolescence in their gender socialization process. Among boys those who were with mixed-sex siblings scored higher on gender-stereotyped traits (ORonly-childvs. mixed-sex siblings = 0.67, 95% CI: 0.48-0.94, p = 0.019; ORsame-sex siblingsvs. mixed-sex siblings = 0.59, 95% CI: 0.37-0.96, p = 0.033). Younger early adolescents aged 10-12 who were the only child or who had mixed-sex siblings perceived more traditional gender role attitudes than those living with same-sex siblings (ORonly-childvs. same-sex siblings = 1.71, 95% CI: 1.06-2.75, p = 0.028; ORmixed-sex siblingsvs. same-sex siblings = 1.74, 95% CI: 1.03-2.94, p = 0.037). Comprehensive sexuality education with gender and power components being well addressed, both in and out of the family, is needed to provide extra gender-inclusive and gender-egalitarian environments for youth.
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Fluorescence sensing can not only identify a target substrate qualitatively but also achieve the purpose of quantitative detection through the change of the fluorescence signal. It has the advantages of immense sensitivity, rapid response, and excellent selectivity. The proposed aggregation-induced emission (AIE) concept solves the problem of the fluorescence of traditional fluorescent molecules becoming weak or quenched in high concentration or aggregated state conditions. Schiff base fluorescent probes have the advantages of simple synthesis, low toxicity, and easy design. They are often used for the detection of various substances. In this review we cover late developments in Schiff base compounds with AIE characteristics working as fluorescence sensors.
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Colorantes Fluorescentes , Bases de Schiff , Fluorescencia , Colorantes Fluorescentes/químicaRESUMEN
More than 85% of colorectal cancer (CRC) patients, who are with microsatellite stability (MSS), are resistant to immune checkpoint blockade (ICB) treatment. To overcome this resistance, combination therapy with chemotherapy is the most common choice. However, many CRC patients do not benefit more from combination therapy than chemotherapy alone. We hypothesize that severe immunosuppression, caused by chemotherapy administered at the maximum tolerated dose, antagonizes the ICB treatment. In this study, we found that low-dose oxaliplatin (OX), an immunogenic cell death (ICD)-induced drug, increased the antitumor response of TIGIT blockade against CT26 tumor, which is regarded as a MSS tumor. Combined treatment with OX and TIGIT blockade fostered CD8+ T-cell infiltration into tumors and delayed tumor progression. Importantly, only low-dose immunogenic chemotherapeutics successfully sensitized CT26 tumors to TIGIT blockade. In contrast, full-dose OX induces severe immunosuppression and impaired the efficacy of combination therapy. Further, we also found that lack of synergy between nonimmunogenic chemotherapeutics and TIGIT blockade. Consequently, this study suggests that the strategies of combination treatment of chemotherapy and ICB should be re-evaluated. The chemotherapeutics should be chosen for the potential to ICD and the dosage and regimen should be also optimized.
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Neoplasias del Colon , Inhibidores de Puntos de Control Inmunológico , Humanos , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Oxaliplatino/farmacología , Oxaliplatino/uso terapéutico , Repeticiones de Microsatélite , Receptores InmunológicosRESUMEN
BACKGROUND: Parenting styles have a tremendous influence on a child's development and behavior. Studies on parenting styles using latent profile analysis have been increasing in recent years. However, there are few such studies conducted in China, especially concerning joint parenting styles (that simultaneously characterize maternal and paternal practices), which are held over the age group of secondary vocational school students. This study aimed to identify the profiles of parenting styles and their associated factors among the parents of secondary vocational school students in China, based on natural samples and not a predetermined model. METHOD: Data were drawn from a cross-sectional study conducted among 3180 students from six secondary vocational schools in Shanghai Municipality and Shaanxi Province. A total of 2392 students who have lived with their parents for most of their lifetime were included in the study. Latent profile analysis was used to identify the profiles of parenting styles of the respondent's parents. Multinominal logistic regression models were used to examine the association between parenting style and demographic characteristics and family background and adolescent outcomes. RESULTS: We identified five latent profiles: "free-range parenting" (27.05%), "behavioral monitoring parenting" (33.65%), "authoritative parenting" (11.75%), "psychological control parenting" (14.38%) and "tiger parenting" (13.17%). The associations between these profiles and adolescent outcomes indicated that these profiles were rational. Participants' gender, grade, residential area, family economic level, parental marital relationship, and parental educational level were predictive factors for parenting styles. CONCLUSIONS: The parenting styles held over secondary vocational school students were somewhat different from Baumrind's parenting style model. A considerable number of students received a parenting style that might predispose them to behavioral and mental health outcomes and merit a tailored intervention using the predictive factors of parenting styles.
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Autoritarismo , Responsabilidad Parental , Adolescente , Niño , China , Estudios Transversales , Humanos , Masculino , Relaciones Padres-Hijo , Responsabilidad Parental/psicología , Estudiantes/psicología , Encuestas y CuestionariosRESUMEN
OBJECTIVES: To investigate the associations between sexual-related knowledge, access to school and family sexuality education, and the experience of sexual intercourse, in order to make recommendations on sexuality education for vocational secondary school students in China. METHODS: A cross-sectional study was conducted among 3180 vocational secondary school students in the Shanghai municipality and the Shaanxi province, China. Data were collected through an online, electronic questionnaire, which included socio-demographics, sexual-related knowledge, sources of information, and sexual-related behaviors. RESULTS: The score on sexual-related knowledge among girls (53.8) is higher than that of boys (48.8), and that of participants from Shanghai (55.2) is higher than their counterparts from Shaanxi (47.6). The proportions of girls (70% and 41.7%, respectively) and participants from Shanghai (65% and 35.7%, respectively) who reported acquiring sexual information from their schools/teachers and parents are higher than that of boys (54.3% and 21.0%, respectively) and their counterparts from Shaanxi (59.7% and 27.4%, respectively). About 6% of participants had experienced sexual intercourse and 10% had watched porn actively. Experience of sexual intercourse was associated with higher sexual-related knowledge scores (OR = 1.01, 95% CI: 1.00-1.02) and active porn watching (OR = 2.63, 95% CI: 1.79-3.84) but was not associated with school and family sexuality education. CONCLUSIONS: Vocational secondary school students had poor sexual knowledge and inadequate school and family sexuality education. School and family-based comprehensive sexuality education should be promoted among vocational secondary school students.
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BACKGROUND: Extreme pre-pregnancy body mass index (BMI) values have been associated with reduced fecundability and prolonged time to pregnancy in previous studies. However, the effect in fertile couples is unclear. OBJECTIVES: This study aimed to evaluate the association between pre-pregnancy BMI and fecundability, measured as time to pregnancy (TTP), among couples that achieved pregnancy within 1 year. METHODS: This was a retrospective cohort study of 50,927 couples wishing to conceive, enrolled in the National Free Preconception Health Examination Project (NFPHEP) in Chongqing, China, during 2012-2016. Participants' weight and height were measured by NFPHEP-trained preconception guidance physicians. TTP measured in months was used to determine subfecundity (TTP >6 months). The strength of association between BMI and TTP/subfecundity was measured with fecundability odds ratios (FOR)/odds ratios (OR) and their corresponding 95% confidence intervals (CI), calculated with Cox and logistic regression analysis. We used restricted cubic spline regression (RCS) to test the observed FOR trends. RESULTS: Compared to women with normal BMI, women with pre-pregnancy overweight/obesity had longer TTP (FOR = 0.96, 95% CI: 0.94-0.99) and increased risk of subfecundity (OR = 1.08, 95% CI: 1.00-1.17). There was no association between TTP and male BMI. RCS trends varied when data were stratified by male pre-pregnancy BMI, with the greatest change detected in pre-pregnancy underweight men. CONCLUSIONS: Pre-pregnancy overweight/obesity was associated with longer TTP and subfecundity among women who became pregnant within 1 year; this effect was likely mediated by their partners' pre-pregnancy BMI. These findings indicate that BMI could affect fecundability, independently of affecting the risk of sterility. Advice on weight management and maintaining healthy weight should be included in couples' preconception guidance.