RESUMO
While 19S proteasome regulatory particle (RP) inhibition is a promising new avenue for treating bortezomib-resistant myeloma, the anti-tumor impact of inhibiting 19S RP component PSMD14 could not be explained by a selective inhibition of proteasomal activity. Here, we report that PSMD14 interacts with NSD2 on chromatin, independent of 19S RP. Functionally, PSMD14 acts as a histone H2AK119 deubiquitinase, facilitating NSD2-directed H3K36 dimethylation. Integrative genomic and epigenomic analyses revealed the functional coordination of PSMD14 and NSD2 in transcriptional activation of target genes (e.g., RELA) linked to myelomagenesis. Reciprocally, RELA transactivates PSMD14, forming a PSMD14/NSD2-RELA positive feedback loop. Remarkably, PSMD14 inhibitors enhance bortezomib sensitivity and fosters anti-myeloma synergy. PSMD14 expression is elevated in myeloma and inversely correlated with overall survival. Our study uncovers an unappreciated function of PSMD14 as an epigenetic regulator and a myeloma driver, supporting the pursuit of PSMD14 as a therapeutic target to overcome the treatment limitation of myeloma.
Assuntos
Histonas , Mieloma Múltiplo , Humanos , Histonas/genética , Complexo de Endopeptidases do Proteassoma/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Bortezomib/farmacologia , Bortezomib/metabolismo , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Linhagem Celular Tumoral , Enzimas Desubiquitinantes/metabolismo , Inibidores de Proteassoma/farmacologia , Transativadores/metabolismoRESUMO
Mobulid species are endangered globally, and the market trade for gill plates is believed to be a major threat. Successful conservation and the sustainable use of mobulids therefore require an objective understanding of consumer characteristics and preferences for gill plates. Previous studies focused on qualitative descriptions, and reliable quantitative analyses are currently lacking. We used a latent class choice experiment method and a semistructured questionnaire to provide important new quantitative information about gill plate consumer characteristics and the heterogeneous nature of demand for gill plates. From May to July 2019, we conducted a field study in Guangzhou, the primary consumption hub for mobulid gill plates in mainland China. Utilizing a simple random sampling method, we engaged in face-to-face interviews with 428 consumers of gill plates in the major trading markets in Guangzhou. Our results showed that 59.8% of consumers of gill plates were over 40 years old, 62.6% were female, 80.7% had annual household incomes of <200,000 yuan, and 84.5% recognized the medical and health value of gill plates and purchased them. About seventy-two percent of consumers preferred to purchase imported and less expensive gill plates from unprotected species, but they had a strong preference for large gill plates from protected species, such as Mobula birostris. This contradiction arose from consumers' lack of knowledge of mobulids and their conservation status. We found, for example, female consumers over 40 years old had the least understanding of conservation status of mobulid species and the link between size of gill plates and rarity of mobulids. This suggests there may be opportunities to promote mobulid conservation through education and marketing targeted at this demographic. Consumers who had a positive preference for gill plates from protected species (regardless of price) (10%) may be harder to influence. Overall, we believe education alone is not enough and that the conservation of mobulids would benefit from an integrated approach that involves conservation education and strengthened trade regulations, such as the introduction of traceability systems and a stiffer legal framework for consumption of protected species.
Características y preferencias de los consumidores de placas branquiales de mobúlidos en China Resumen Las especies de mobúlidos están en peligro de extinción en todo el mundo y se considera al mercado de placas branquiales como una amenaza principal. Por lo tanto, la conservación exitosa y el uso sustentable de los mobúlidos requiere del entendimiento objetivo de las características y preferencias de los consumidores de estas placas branquiales. Los estudios previos se han enfocado en descripciones cualitativas, por lo que actualmente no hay suficientes análisis cuantitativos confiables. Usamos un método de experimento de elección de clase latente y un cuestionario semiestructurado para proporcionar información cuantitativa nueva e importante sobre las características de los consumidores de placas branquiales y la naturaleza heterogénea de la demanda de estas placas. Realizamos un estudio de campo entre mayo y julio de 2019 en Guangzhou, el principal centro de consumo de placas branquiales de mobúlidos en el interior de China. Utilizamos un método de muestreo aleatorio simple para entrevistar caraacara a 428 consumidores de placas branquiales en los principales mercados de Guangzhou. Nuestros resultados mostraron que el 59.8% de los consumidores son mayores a 40 años, 62.6% son mujeres, 80.7% tienen un ingreso doméstico anual mayor a 200,000 yuan y 84.5% reconocieron el valor médico y para la salud que tienen las placas branquiales, razones por las que las compran. El 72% de los consumidores prefirió comprar las placas importadas y menos caras de especies no protegidas, aunque tuvieron una mayor preferencia por las placas más grandes de las especies protegidas, como Mobula birostris. Esta contradicción se debe a la falta de conocimiento que tienen los consumidores sobre los mobúlidos y su estado de conservación. Descubrimos que, por ejemplo, las consumidoras de más de 40 años tienen el menor conocimiento del estado de conservación de los mobúlidos y la conexión entre el tamaño de las placas branquiales y la rareza de la especie. Lo anterior sugiere que podría haber oportunidad de promover la conservación de los mobúlidos por medio de la educación y la mercadotecnia enfocada en este grupo demográfico. Podría ser más difícil influir sobre el 10 % de los consumidores, el cual tiene una preferencia positiva por las placas branquiales de las especies protegidas (sin importar el precio). En general creemos que la educación por sí sola no es suficiente y que la conservación de los mobúlidos se beneficiaría de una estrategia integrada que involucre la educación para la conservación y regulaciones de mercado fortalecidas, como la introducción de los sistemas de trazabilidad y un marco legal más rígido para el consumo de las especies protegidas.
Assuntos
Conservação dos Recursos Naturais , Comportamento do Consumidor , China , Animais , Adulto , Feminino , Masculino , Conservação dos Recursos Naturais/métodos , Humanos , Pessoa de Meia-Idade , Espécies em Perigo de ExtinçãoRESUMO
BACKGROUND: Diabetic kidney disease (DKD) is the most common microvascular complication of diabetes, which has been a major cause of end-stage renal failure. Diagnosing diabetic kidney disease is important to prevent long-term kidney damage and determine the prognosis of patients with diabetes. In this study, we investigated the clinical significance of combined detection of urine orosomucoid and retinol-binding protein for early diagnosis of diabetic kidney disease. METHODS: We recruited 72 newly diagnosed patients with type 2 diabetes and 34 healthy persons from August 2016 to July 2018 at the First Affiliated Hospital of Henan Polytechnic University (Jiaozuo Second People's Hospital). Using the Mogensen grading criteria, participants were classified as having diabetes or diabetic kidney disease, and healthy persons constituted the control group. Urine orosomucoid and retinol-binding protein levels were measured and correlated with other variables. RESULTS: With the aggravation of renal damage, the level of urinary mucoid protein gradually increased. Urinary retinol-binding protein and microalbumin levels were significantly higher in the diabetes group than in control and nephropathy groups. Orosomucoid and retinol-binding protein might be independent risk factors for diabetes and diabetic kidney disease. Urinary orosomucoid significantly correlated with retinol-binding protein and microalbumin levels in the diabetic kidney disease group. CONCLUSION: Elevated urine orosomucoid and retinol-binding protein levels can be detected in the early stages of type 2 diabetic kidney disease. Both of these markers are important for diabetic kidney disease detection and early treatment.
Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Humanos , Orosomucoide/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Rim , Proteínas de Ligação ao Retinol/urina , BiomarcadoresRESUMO
BACKGROUND: The Architect HIV Ag/Ab Combo has been implemented worldwide as a screening test for more than ten years. However, its high sensitivity may lead to false-positive results in a low-prevalence setting. METHODS: This study was carried out to evaluate the performance of the Architect HIV Ag/Ab Combo based on the sample-to-cutoff (S/CO) ratios, to explore the optimal cutoff value to predict HIV infection and reduce the frequency of false-positive results. A retrospective analysis of clinical samples using the Architect HIV Ag/Ab Combo between July 2011 and February 2020 was performed. The sensitivity, specificity, positive predictive value (PPV), and false-positive rate (FPR) were evaluated and the receiver operating characteristic curve (ROC) analysis was used to determine the optimal cutoff value to predict HIV infection. RESULTS: During the study period, 531 out of 692,155 samples were repeatedly reactive by the Architect HIV Ag/Ab Combo. The median S/CO value of HIV-positive were significantly higher than that of false-positive. The PPV of males (85.68%) was significantly higher than that of females (47.89%). The optimal cutoff value estimated by ROC analysis was 8.96 with the highest sum of sensitivity (100.00%) and specificity (100.00%) for males. However, for females, the optimal cutoff value was 26.97 with the highest sum of sensitivity (100.00%) and specificity (100.00%). CONCLUSIONS: For the Architect HIV Ag/Ab Combo, the optimal cutoff value needs to be set for the different genders to predict the final status of HIV infection reliably.
Assuntos
Infecções por HIV , HIV-1 , Reações Falso-Positivas , Feminino , Anticorpos Anti-HIV , Antígenos HIV , Infecções por HIV/diagnóstico , HIV-2 , Humanos , Imunoensaio/métodos , Masculino , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
DNA damage-induced NF-κB activation and the secretion of inflammatory cytokines play crucial roles in carcinogenesis and cellular senescence. However, the underlying mechanisms, especially the initial sensors and transducers connecting the nuclear DNA damage signal with cytoplasmic NF-κB activation remain incompletely understood. Here, we report that TRAF-interacting protein with forkhead-associated domain (TIFA), an established NF-κB activator in the cytosol, unexpectedly exhibited nuclear translocation and accumulation on damaged chromatin following genotoxic stress. Accordingly, we also found that DNA damage-induced transcriptional activation and the resulting secretion of classic NF-κB targets, including interleukin (IL)-6 and IL-8, was greatly enhanced in TIFA-overexpressing cells compared with control cells. Mechanistically, DNA damage-induced TIFA phosphorylation at threonine 9 (pThr-9), and this phosphorylation event, involving the pThr-binding forkhead-associated domain, was crucial for its enrichment on damaged chromatin and subsequent NF-κB activation. Moreover, in conjunction with its partner protein, the E3 ligase TNF receptor-associated factor 2 (TRAF2), TIFA relayed the DNA damage signals by stimulating ubiquitination of NF-κB essential modulator (NEMO), whose sumoylation, phosphorylation, and ubiquitination were critical for NF-κB's response to DNA damage. Consistently, TRAF2 knockdown suppressed TIFA overexpression-enhanced NEMO ubiquitination under genotoxic stress, and a unphosphorylatable Thr-9-mutated TIFA variant had only minor effects on NEMO poly-ubiquitination. Finally, in agreement with the model of DNA damage-associated secretory senescence barrier against carcinogenesis, ectopic TIFA expression limited proliferation of multiple myeloma cancer cells. In conclusion our results indicate that TIFA functions as a key transducer in DNA damage-induced NF-κB activation.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Dano ao DNA , NF-kappa B/metabolismo , Peptídeos e Proteínas Associados a Receptores de Fatores de Necrose Tumoral/metabolismo , Carcinogênese , Proliferação de Células , Cromatina/metabolismo , Células HEK293 , Células HeLa , Humanos , Quinase I-kappa B/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Mutagênicos/toxicidade , Fosforilação , Ligação Proteica , Transdução de Sinais , Fator 2 Associado a Receptor de TNF/metabolismo , UbiquitinaçãoRESUMO
The contamination of wetlands by heavy metals, exacerbated by agricultural activities, presents a threat to both organisms and humans. Heavy metals may undergo trophic transfer through the food web. However, the methods for quantifying the bioaccumulation and trophic transfer processes of heavy metals based on the food web remains unclear. In this study, we employed stable isotope technology to construct a quantitative oriental white stork's typical food web model under a more accurate scaled Δ15N framework. On this basis, the concentrations for heavy metal (Cu, Zn, Hg, Pb) were analyzed, we innovatively visualized the trophic transfer process of heavy metals across 13 nodes and 45 links and quantified the transfer flux based on the diet proportions and heavy metal concentrations of species, taking into account biomagnification effects and potential risks. Our findings revealed that as for Cu and Pb, the transfer flux level was consistent with diet proportion across most links. While Hg and Zn transfer flux level exceeded the corresponding diet proportion in the majority of links. In summary, Hg exhibited a significant biomagnification, whereas Cu, Zn, Pb experienced biodilution. The fish dietary health risk assessment for fish consumers showed that Hg, Pb posed certain risks. This research marks a significant step forward in the quantitative assessment of multi-link networks involving heavy metals within the food web.
Assuntos
Bioacumulação , Monitoramento Ambiental , Cadeia Alimentar , Metais Pesados , Poluentes Químicos da Água , Áreas Alagadas , Metais Pesados/análise , Metais Pesados/metabolismo , China , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/análise , Animais , Água Doce , Peixes/metabolismoRESUMO
Pheochromocytomas (PCCs) are rare neuroendocrine tumors that originate from chromaffin cells in the adrenal gland. However, the cellular molecular characteristics and immune microenvironment of PCCs are incompletely understood. Here, we performed single-cell RNA sequencing (scRNA-seq) on 16 tissues from 4 sporadic unclassified PCC patients and 1 hereditary PCC patient with Von Hippel-Lindau (VHL) syndrome. We found that intra-tumoral heterogeneity was less extensive than the inter-individual heterogeneity of PCCs. Further, the unclassified PCC patients were divided into two types, metabolism-type (marked by NDUFA4L2 and COX4I2) and kinase-type (marked by RET and PNMT), validated by immunohistochemical staining. Trajectory analysis of tumor evolution revealed that metabolism-type PCC cells display phenotype of consistently active metabolism and increased metastasis potential, while kinase-type PCC cells showed decreased epinephrine synthesis and neuron-like phenotypes. Cell-cell communication analysis showed activation of the annexin pathway and a strong inflammation reaction in metabolism-type PCCs and activation of FGF signaling in the kinase-type PCC. Although multispectral immunofluorescence staining showed a lack of CD8+ T cell infiltration in both metabolism-type and kinase-type PCCs, only the kinase-type PCC exhibited downregulation of HLA-I molecules that possibly regulated by RET, suggesting the potential of combined therapy with kinase inhibitors and immunotherapy for kinase-type PCCs; in contrast, the application of immunotherapy to metabolism-type PCCs (with antigen presentation ability) is likely unsuitable. Our study presents a single-cell transcriptomics-based molecular classification and microenvironment characterization of PCCs, providing clues for potential therapeutic strategies to treat PCCs.
Assuntos
Neoplasias das Glândulas Suprarrenais , Feocromocitoma , Humanos , Feocromocitoma/genética , Microambiente Tumoral , Neoplasias das Glândulas Suprarrenais/genética , Apresentação de Antígeno , Linfócitos T CD8-PositivosRESUMO
PURPOSE: To investigate the remodeling of multiple myeloma (MM) microenvironment after BCMA-targeted chimeric antigen receptor T cell (CAR-T) therapy. EXPERIMENTAL DESIGN: We performed single-cell RNA sequencing (scRNA-seq) on paired bone marrow specimens (n = 14) from 7 MM patients before (i.e., baseline, 'day -4') and after (i.e., 'day 28') post-lymphodepleted BCMA CAR-T therapy. RESULTS: Our analysis revealed heterogeneity in gene expression profiles among MM cells, even those harboring the same cytogenetic abnormalities. The best overall responses (BORs) of patients over the 15-month follow-up are positively correlated with the abundance and targeted cytotoxic activity of CD8+ effector CAR-T cells on day 28 after CAR-T cell infusion. Additionally, favorable responses are associated with attenuated immunosuppression mediated by regulatory T cells (Tregs), enhanced CD8+ effector T cell cytotoxic activity, and elevated type 1 conventional dendritic cell (cDC1) antigen presentation ability. DC re-clustering inferred intramedullary-originated cDC3s with extramedullary migration. Cell-cell communication network analysis indicated BCMA CAR-T therapy mitigates BAFF/GALECTIN/MK pathway-mediated immunosuppression and activates MIF pathway-mediated anti-MM immunity. CONCLUSIONS: Our study sheds light on MM microenvironment dynamics after BCMA CAR-T therapy, offering clues for predicting treatment responsivity.
RESUMO
Scientific understanding of trophic magnification factors (TMFs) is conducive to formulating environmental management measures. Trophic position (TP) of species is the key parameter in TMFs assessment. Nitrogen stable isotopes (δ15N) provide a powerful tool to estimate TP. However, some limitations could introduce considerable uncertainty into TP and TMFs assessment which mainly includes: 1) determination of Δ15N between two adjacent trophic positions; 2) determination of baseline species. Different from the widely used constant Δ15N (3.4 ) between two adjacent trophic positions, which is called additive Δ15N framework, Δ15N gradually decreases as trophic position increases under scaled Δ15N framework, which has been confirmed by more and more laboratory studies and meta-analyses. In this study, we sampled in two similar littoral ecosystems separated by one natural dam, which is called Small Xingkai Lake and Xingkai Lake, analyzed the δ15N and total mercury (THg) of each species. On the one hand, we compared the TP of species under the additive Δ15N framework and scaled Δ15N framework with the White shrimp (Exopalaemon modestus) as baseline species in two lakes respectively. On the other hand, we explored the possible changes in TMFs based on TP. Our results show, under the scaled Δ15N framework, the trophic position of the same species is higher, while TMFs is lower compared with the additive Δ15N framework; even if in the two interconnected lakes, distributed the same baseline species, in the similar ecosystem, separate baselines should also be used. In this study, two frameworks of the food chain were compared in two interconnected freshwater ecosystems for the first time. The difference between TMFs of two lakes was obvious under scaled framework but not under additive framework. We also recommend that future TMFs assessments should be based on the scaled Δ15N framework because it has improved the accuracy of trophic position assessment.
Assuntos
Mercúrio , Poluentes Químicos da Água , Animais , Ecossistema , Peixes , Cadeia Alimentar , Mercúrio/análise , Lagos , Isótopos de Nitrogênio/análise , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodosRESUMO
In this communication, we report a new class of oscillation mode, dome-shaped mode (DSM), in liquid crystal (LC) microlasers. A record high Q-factor over 24 000 is achieved in LC soft-matter microlasers. We successfully presented a proof-of-concept demonstration of red, green, blue (RGB) LC-DSM microlaser pixels with a 74% broader achievable color gamut than the standard RGB color space. Besides, the detection limit for acetone vapor molecules is as low as 0.5 ppm, confirming the excellent potential of the proposed LC-DSM microlaser in ultra-high sensitivity detection.
RESUMO
Objective: This research mainly discusses the influence of prehospital emergency care (PHEC) on the rescue success rate and complication rate of senile patients with acute myocardial infarction (AMI). Methods: We selected 200 senile AMI patients who visited between January 2019 and January 2021, and retrospectively analyzed their clinical data. According to the differences in nursing methods, the patients were assigned to control group (n = 90) and observation group (n = 110), which were treated with routine nursing and PHEC, respectively. Intergroup comparisons were made in terms of rescue success rate, nursing efficacy, clinical parameters and complication rate. Results: After investigation, the nursing efficacy was higher in the observation group compared with the control group. Additionally, the observation group was observed with statistically shorter time to thrombolysis and hospital stay, as well as evidently lower mortality and complication rates. Conclusion: The above demonstrates that PHEC can effectively improve the rescue success rate and rescue efficacy, and facilitate the recovery of senile AMI patients, with a low complication rate compared with the routine care, which plays an important role in ensuring patients' life safety and is worth popularizing clinically.
Assuntos
Serviços Médicos de Emergência , Infarto do Miocárdio , Humanos , Terapia Trombolítica , Estudos Retrospectivos , Infarto do Miocárdio/terapiaRESUMO
As an electric current passes through an organic semiconductor, a small number of organic molecules will inevitably act as a polaron state that is similar to an ionic charged state. The continuous device operation of organic semiconducting molecules is directly associated with the stability of the charged state. Herein, we choose the high-performance Y-series of nonfullerene acceptors to investigate the stability by a spectro-electrochemical technique. The results reveal the discoloration of molecules in the charged state and can be partially recovered after neutralization with about 10% irreversible part. It is found that the degree of the irreversible process is associated with halogen substituents at the end groups, and the irreversible reactions are also discussed. Our results reveal that the stability of a charged state can be improved by the fine-tuning of the molecular structures, and the local charge density can also be rapidly reduced by the high carrier mobility, the key factor to improving the stability of nonfullerene acceptors for better practical applications.
RESUMO
In recently developed organic semiconductors, the continuously improving sample purity makes the stability of the chemical bonds of organic materials themselves become a key factor in device stability, which provides greater uncertainty for the generation of "zeroth defect", and the spatial resolution of performance at different positions becomes particularly important. In this work, complete maps of electroluminescent, photoluminescent, and Raman scattering in the same area on an organic light-emitting diode during its operation have been achieved with a confocal spectrometer with multiple laser sources. The different spectral characters help to establish different regions and suggest the mechanism of degradation. In particular, Raman scattering has been shown to be very sensitive in a multilayer device to a change in thickness of several nanometers. In amorphous films with few defects, the very weak film uniformity, including the thickness and degree of aggregation, would induce dramatic degradation. The relatively thin and/or loosely textured region easily locally overheats and has the highest probability of "zeroth defect" generation. This method has high spatial resolution, a low level of damage to samples, good reproducibility, and multiple interconnected pieces of information, which is significant for online quality prediction and mechanistic analysis.
RESUMO
Different from the widely used constant discrimination factor Δ15N = 3.4 between two adjacent trophic positions (TPs), a scaled Δ15N framework for evaluating the TP of species was developed in 2014, that is, the Δ15N between two adjacent TPs decreases as the TP increases which is considered to be in closer conformity to the trophic cascade in the natural food web. In this study, we compared the two TP calculation methods and then reconsidered the evaluation of the trophic magnification factors (TMFs). Our results show that the TPscaled value is higher and the TMFs value is lower under the scaled Δ15N framework, indicating that the TMFs value under the constant Δ15N framework is often overestimated. We further constructed a diet proportion food web model, which shows that species with lower TP has higher contribution rate as food sources. In Xingkai Lake, the enrichment process of mercury in the food web is not strictly consistent with the diet proportion of the food web. Based on the diet proportion food web model and the mercury enrichment model, it can be found that the White shrimp (Exopalaemon modestus) is not only an important food source, but also the main source of mercury transmission in the food web. Overall, our findings have quantified the food web construction and thus facilitated a better understanding of the interaction between the diet proportion and the bio-concentration in the food web.
Assuntos
Mercúrio , Poluentes Químicos da Água , Animais , Monitoramento Ambiental/métodos , Peixes , Cadeia Alimentar , Lagos , Mercúrio/análise , Isótopos de Nitrogênio/análise , Poluentes Químicos da Água/análiseRESUMO
The pro-inflammatory activation of microglia is a hallmark of Alzheimer's disease (AD), and this process involves a switch from oxidative phosphorylation (OXPHOS) toward glycolysis. Here, we show how a positive feedback loop in microglia drives AD pathogenesis, and we demonstrate that inhibiting this cycle in microglia can ameliorate Aß burden and cognitive deficits in an AD mouse model (5XFAD). After first detecting elevated histone lactylation in brain samples from both 5XFAD mice and individuals with AD, we observed that H4K12la levels are elevated in Aß plaque-adjacent microglia. This lactate-dependent histone modification is enriched at the promoters of glycolytic genes and activates transcription, thereby increasing glycolytic activity. Ultimately, the glycolysis/H4K12la/PKM2 positive feedback loop exacerbates microglial dysfunction in AD. Pharmacologic inhibition of PKM2 attenuated microglial activation, and microglia-specific ablation of Pkm2 improved spatial learning and memory in AD mice. Thus, our study illustrates that disruption of the positive feedback loop may be a potential therapeutic approach for the treatment of AD.
Assuntos
Doença de Alzheimer , Retroalimentação Fisiológica , Glucose , Histonas , Microglia , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides , Animais , Modelos Animais de Doenças , Glucose/metabolismo , Histonas/genética , Histonas/metabolismo , Lisina/metabolismo , Camundongos , Camundongos Transgênicos , Microglia/metabolismoRESUMO
Sustainable wildlife management (SWM) is based on a synergy of traditional/local knowledge, advances in scientific knowledge, and fast-evolving economic and social circumstances. A widely accepted cornerstone of SWM globally is that conservation and utilization need to be effectively integrated, emphasizing the benefits humans can derive from biodiversity, thereby further encouraging people to protect and value wildlife though its management. However, with demand from biological resources growing at an unprecedented rate and the emergence of social media, conservationists must respond quickly to new challenges and conflicts associated with species management and public policy. For example, the rise of the "Compassionate Conservation" (CC) movement, fueled by social marketing and media, which promotes the welfare of individual animals, has introduced a set of challenges for conventional conservation management as it opposes most or all forms of wildlife utilization and hunting. CC advocates are increasingly influential at global and national policy levels; hence, it is imperative that conservationists are informed and aware of the future challenges from a rapidly changing global society. In this paper, we report the findings of a large semi-structured questionnaire in China which investigated the attitude of the urban public toward sustainable wildlife management (SWM) and wildlife conservation across a range of issues and identified the key socio-economic and demographic factor drivers for those attitudes. The survey was conducted from November 2018 to October 2020, across 15 cities randomly selected among China's seven administrative geographic regions. The survey was initially conducted through face-to-face interviews, but later, due to COVID-19 restrictions, was completed via online questionnaires. A Likert seven-point scale method was used to score the public's degree of agreement or disagreement for each question; a multivariate stepwise linear regression method was used to analyze whether the overall attitude of the respondents toward SWM and wildlife conservation was affected by their demographic characteristics; and a classification and regression tree (CART) was used to conduct an in-depth analysis of the issues with negative scores in the questionnaire, so as to understand how the respondents' demographic characteristics affected the public's attitude about such issues, which could supplement results obtained from the multivariate stepwise linear regression analysis. The results show that the public are broadly supportive of SWM, but only moderately so. On issues of "Animal Welfare and Rights," "Wildlife Utilization and Captive Breeding," and "Trophy Hunting", the core concerns of the "Compassionate Conservation" movement and the overall public view are more antagonistic to conventional SWM. We also find specific demographic characteristics significantly influence attitudes about SWM, with vegetarians, those with religious beliefs, and with lower educational standards demonstrating weaker support for SWM. For younger people, "Animal Welfare and Rights" is a special concern, hence, we identify this as a key issue to be addressed for SWM and conservation in the future. Our research suggests that conservation organisations may need to adapt their management aims and practices to avoid direct conflict with the rising tide of animal rights sentiment, especially among the young. Furthermore, significant investment will be required to promote science-based conservation in social marketing on all social media platforms to help educate and engage the public with the science behind conservation management.
RESUMO
The widespread dissemination of information related to wildlife utilization in new online media and traditional media undoubtedly impacts societal conservation concepts and attitudes, thus triggering public discussions on the relationship between conservation and utilization. A study on how public attitudes and concepts are affected by the related information on wildlife utilization is helpful to implement the scientific wildlife conservation and management strategies, and to propose targeted measures to optimize the information environment. We designed the questionnaire to investigate the public's awareness and agreement with related information on wildlife utilization so as to measure how information with different dissemination channels, source types, and content orientation influenced the public's concept of wildlife conservation and utilization. The questionnaire was distributed in seven major geographical regions throughout China. Out of a total of 1645 questionnaires that were collected, 1294 questionnaires were valid, with an effective rate of 78.7%. Results show that respondents had the greatest awareness of information on preventing unsustainable and illegal utilization, and the lowest awareness of information on promoting unsustainable utilization, and that awareness of information that against utilization was higher than that of information which supported sustainable utilization. At the same time, respondents showed the greatest agreement for information on preventing unsustainable utilization and the lowest agreement for information on promoting unsustainable utilization; also, their agreement with information that against utilization was higher than that for information which supported sustainable use. Respondents had a high level of awareness of information on wildlife related to COVID-19 provided by experts. Gender, age, the level of development of the city in which they live, education, vegetarianism, and religious beliefs all affected respondents' agreement with related information on wildlife utilization. This research suggests that the publicity and education of scientific conservation methods should be emphasized in the future conservation education. In addition, scholars in the field of wildlife research should assume the role of 'influencer' and give full play to the scientific guidance of public opinion.
RESUMO
Biochemistry is an important curriculum for all medical students but has long been considered obscure and of very little or indirect relevance to medical or clinical practice, which markedly diminishes the enthusiasm and motivation of medical students in learning. Biochemistry teachers always face a tremendous challenge to deliver an attractive and high-quality lecture class. Inspired by convincing studies that show numerous benefits of undergraduate research, we tried to modify our teaching method in the past 5 years by incorporating classical scientific research stories into our traditional lecture class, such as the discovery of the semi-conservative DNA replication, telomeric DNA and telomerase, the tricarboxylic acid cycle (TCA cycle), and so on. Through this story-based teaching, we not only helped them deeply understand the textbook content, but also introduced the process of real scientific research to the students in an interesting way. Our efforts aim to combine the delivery of knowledge with the inspiration of students' active learning. We found that most students involved in our classes responded positively. As described in the survey, they were strongly attracted by those research stories; rather than feeling bored about the Biochemistry textbook, they experienced curiosity which fostered their active learning. They also learned to appreciate the beauty of science. More importantly, their impression on how the authentic science research was done was instructive for their critical thinking.
Assuntos
Bioquímica/educação , Disseminação de Informação/métodos , Motivação , Narração , Aprendizagem Baseada em Problemas/métodos , Estudantes de Medicina/psicologia , Pensamento , Currículo , Humanos , EnsinoRESUMO
We report on 16 children with ingestion of magnetic foreign bodies, who were identified by a medical record review of our hospital data for the time period between January, 2017 and May, 2018. Digestive tract wall was sandwiched in 13 (75%) children and 11 (74%) had gaptic intestinal perforation.
Assuntos
Corpos Estranhos , Perfuração Intestinal , Criança , Corpos Estranhos/complicações , Corpos Estranhos/diagnóstico por imagem , Humanos , Perfuração Intestinal/etiologia , Perfuração Intestinal/cirurgia , ImãsRESUMO
Many carcinomas feature hypoxia, a condition has long been associated with tumor progression and poor prognosis, as well as resistance to chemoradiotherapy. Here, we report that the F-box protein JFK promotes mammary tumor initiation and progression in MMTV-PyMT murine model of spontaneous breast cancer. We find that JFK is inducible under hypoxic conditions, in which hypoxia-inducible factor HIF-1α binds to and transcriptionally activates JFK in breast cancer cells. Consistently, analysis of public clinical datasets reveals that the mRNA level of JFK is positively correlated with that of HIF-1α in breast cancer. We show that JFK deficiency leads to a decrease in HIF-1α-induced glycolysis in breast cancer and sensitizes hypoxic breast cancer cells to ionizing radiation and chemotherapeutic treatment. These results indicate that JFK is an important player in hypoxic response, supporting the pursuit of JFK as a potential therapeutic target for breast cancer intervention.