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Background: Microplastics (MPs) has been rapidly increasing and interacting with wildlife. As the highest altitudes inhabited non-human primate, Yunnan snub-nosed monkey (Rhinopithecus bieti) have been proven to be an umbrella and flagship species to indicate ecosystem changes and help develop environmental management strategies. In this study, we aimed to investigate the behavioral and ecological reasons for the types, content and differences of MPs in the feces of R. bieti, and explored the effects of MPs on gut microbiome of R. bieti. Methods: We used the Agilent 8700 LDIR to identify the abundance and size distribution of MPs in fecal samples, and then analyzed the causes of differences in MPs content by combining data from different populations (wild group, provisioned wild group) and dominance hierarchy. At the same times, the relationships were investigated between gut microbiome diversity and MPs content. Results: We first demonstrate MPs ingestion by R. bieti, which highlights the potential impacts of MPs pollution in such high-altitude, inaccessible protected areas. A total of 36 types of MPs were detected, with an average of 75.263 ± 58.141MPs/g. Food provisioning and tourism significantly increased the content of MPs in the feces of R. bieti, but tourism alone did not significantly increase the content of MPs as food provisioning. At the same time, the study found that there was no significant difference in the content of MPs between different sex groups, however, the feces MPs content of adult R. bieti was significantly lower than that of juvenile, and the social dominance hierarchies among OMUs was positively correlated with the exposure of MPs. The current level of MPs pollution did not cause gut microbiome dysbiosis of R. bieti. Conclusion: Our study proved from behavioral and ecological perspectives that the R. bieti exposure to MPs was related to provisioned food, and was closely related to dominance hierarchy and age. From the perspective of intestinal microbiology, it was proved that the current intake of MPs did not cause gut microbiome dysbiosis of R. bieti. Our study provided scientific basis for formulating effective protection measures and promoting the effective protection of rare and endangered animals.
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Species geographic distribution and conservation priority areas are important bases for in situ biodiversity conservation and conservation decision-making. In view of the urgency of endangered species protection, eight representative endangered species in the typical forest ecosystem of the Greater and Lesser Khingan Mountains were studied. Based on 1127 occurrence points and environmental data collected from 2016 to 2021, used BIOMOD2 and Zonation to reconstruct the potential distribution area and identify conservation priority areas of eight species (Tetrao parvirostris, T. tetrix, Gulo gulo, Alces alces, Martes zibellina, Moschus moschiferus, Lynx lynx, Lutra lutra). The results showed potential distribution areas for almost all species concentrated in the northern part of the Greater Khingan Mountains (GKM) and the central part of the Lesser Khingan Mountains (LKM). The potential distribution areas of each species were as follows: black-billed capercaillie, 102,623 km2; black grouse, 162,678 km2; wolverine, 63,410 km2; moose, 140,287 km2; sable, 112,254 km2; Siberian musk deer, 104,787 km2; lynx, 139,912 km2; and Eurasian otter, 49,386 km2. Conservation priority areas (CPAs) clustered in the north GKM and central LKM and totaled 220,801 km2, and only 16.94% of the CPAs were currently protected by nature reserves. We suggest that the Chinese government accelerate the integration of existing protected areas in the northern GKM and establish a larger GKM National Park based on cost-effective multi-species protection.
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Iron contributes to tumor initiation and progression; however, excessive intracellular free Fe2+ can be toxic to cancer cells. Our findings confirmed that multiple myeloma (MM) cells exhibited elevated intracellular iron levels and increased ferritin, a key protein for iron storage, compared with normal cells. Interestingly, Bortezomib (BTZ) was found to trigger ferritin degradation, increase free intracellular Fe2+, and promote ferroptosis in MM cells. Subsequent mechanistic investigation revealed that BTZ effectively increased NCOA4 levels by preventing proteasomal degradation in MM cells. When we knocked down NCOA4 or blocked autophagy using chloroquine, BTZ-induced ferritin degradation and the increase in intracellular free Fe2+ were significantly reduced in MM cells, confirming the role of BTZ in enhancing ferritinophagy. Furthermore, the combination of BTZ with RSL-3, a specific inhibitor of GPX4 and inducer of ferroptosis, synergistically promoted ferroptosis in MM cell lines and increased cell death in both MM cell lines and primary MM cells. The induction of ferroptosis inhibitor liproxstatin-1 successfully counteracted the synergistic effect of BTZ and RSL-3 in MM cells. Altogether, our findings reveal that BTZ elevates intracellular free Fe2+ by enhancing NCOA4-mediated ferritinophagy and synergizes with RSL-3 by increasing ferroptosisin MM cells.
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Bortezomib , Sinergismo Farmacológico , Ferritinas , Ferroptosis , Hierro , Mieloma Múltiple , Coactivadores de Receptor Nuclear , Humanos , Mieloma Múltiple/metabolismo , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/patología , Coactivadores de Receptor Nuclear/metabolismo , Coactivadores de Receptor Nuclear/genética , Bortezomib/farmacología , Ferritinas/metabolismo , Ferroptosis/efectos de los fármacos , Hierro/metabolismo , Línea Celular Tumoral , Autofagia/efectos de los fármacos , Antineoplásicos/farmacología , CarbolinasRESUMEN
Solar and radiative warming are smart approaches to maintaining the human body at a metabolically comfortable temperature in both indoor and outdoor scenarios. Nevertheless, existing warming textiles are ineffective in frigid climates because the solar absorption of selective absorbing coating is significantly reduced when coated on rough textile surface. Herein, for the first time, high-entropy nitrides based spectrally selective film (SSF) is introduced on common cotton through a one-step magnetron sputtering method. The well-designed refractive index gradient enables destructive interference effects, offering a roughness-insensitive high solar absorptance (92.8%) and low thermal emittance (39.2%). Impressively, the solar absorptance is 9.1% higher than the reported best-performing selective nanofilm-based textile. As a result, such a textile achieves a record-high photothermal conversion efficiency (82.2% under 0.6 suns, at 0 °C). This textile yields a 3.5 °C drop in the set-point of indoor air-conditioner temperature. Besides, in a winter morning with an air temperature of 7.5 °C, it warms up the human skin by as large as 12 °C under weak sunlight (350 W m-2 ). More importantly, such a superior radiative warming performance is achieved by engineering the widely used cotton without compromising its breathability and durability, showing great potential for practical applications.
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Harvesting solar energy to enhance thermoelectric generator efficiency is a highly effective strategy. However, it is a grand challenge but essential to increase solar-thermal conversion efficiency. A spectrally selective absorber, which is capable of boosting solar absorptance (α) while suppressing thermal emittance (ε), shows great potential to elevate the solar-thermal conversion efficiency. Herein, we fabricate a multilayer spectrally selective absorber with the assistance of high-entropy nitrides, which shows outstanding spectral selectivity (α/ε = 95.2/10.9%). Benefitting from the high-entropy nitrides, it is experimentally demonstrated that the as-deposited absorber exhibits superior thermal stability, which is crucial to ensure service life. Under 1000 W·m-2 simulated solar illumination, it achieves a very high surface temperature of 109.6 °C, making it suitable to enhance the efficiency of solar thermoelectric generators. Impressively, the integration of the proposed absorber with a commercial thermoelectric generator efficiently reinforces thermoelectric performance, offering a high output power of 1.99 mW. More importantly, by taking advantage of a thermal concentration strategy, it enables a further increase of the output power by 2.98 mW. This work provides a promising solar-thermal material to boost high thermoelectric performance and extends the application category of high-entropy nitrides.
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Interest on the nonlinear optical (NLO) switches that turn on/off the second-harmonic generation (SHG) triggered by the external stimulus (such as heat) have continuously grown, especially on the solid-state NLO switches showing superior stability, reversibility, and reproducibility. Herein, we discover (NH4)2PO3F, as an entirely new solid-state NLO switch showing outstanding switch contrast and reversibility as well as strong SHG intensity (1.1 × KH2PO4 (KDP)) and high laser-induced damage threshold (2.0 × KDP), undergoes a unique first-order phase transition that originates from a reversible hydrogen-bond rearrangement and needs to overcome an energy barrier. Accordingly, we put forward a strategy to continuously modify such an energy barrier by reducing the number of hydrogen bonds per unit cell via an isoelectronic replacement of NH4+ by K+ with a similar size yet incapability of providing any hydrogen bond. Consequently, Kx(NH4)2-xPO3F (x = 0-0.3) exhibiting excellent switching performance are obtained. Remarkably, Kx(NH4)2-xPO3F not only realizes a continuously tunable Tc spanning from 270 to 150 K, representing the widest NLO switching temperature range ever known but also indicates the first solid-state NLO switch example with continuous Tc. Intrinsically, such a Tc decline depends on the weakening degree of the hydrogen-bonding interactions in the unit cell. These new insights will shed useful light on the future material design and open new application possibilities.
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BACKGROUND: Chronic myeloid leukemia (CML) is a type of cancer that starts in certain blood-forming cells of the bone marrow. LncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a well known protooncogene, has be shown to be upregulated in various tumor types, including multiple myeloma. However, the biological function of MALAT1 in CML remains has yet to be explored. This study was designed to investigate the effects of MALAT1 on the physiological processes in CML and its underlying mechanisms, which will be helpful for us to have a better understanding of CML development and progression as well as improved therapeutic method. METHODS: Recombinant virus construction and infection was performed to overexpress or knockdown the expression of MALAT1. Dual luciferase reporter assay was applied to vetify the interaction between MALAT1 and miR-328. The cell viability and cell cycle were analyzed by CCK-8 assay and flow cytometry, respectively. Quantitative real time PCR and western blotting assays were used to measure the expression of genes and proteins. RESULTS: The expression of MALAT1 was significantly increased in CML cells compared with peripheral blood cells from health donors. Silencing of MALAT1 significantly inhibited the proliferation and arrested cell cycle of CML cells by targeting miR-328. Moreover, MALAT1 knockdown enhanced imatinib sensitivity of K562â¯cells, while silencing of miR-328 abolished this effect. CONCLUSIONS: These findings indicate that lncRNA MALAT1/miR-328 axis promotes the proliferation and imatinib resistance of CML cells, providing new perspectives for the future study of MALAT1 as a therapeutic target for CML.
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Resistencia a Antineoplásicos/genética , Mesilato de Imatinib/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , Secuencia de Bases , Proteínas Potenciadoras de Unión a CCAAT/genética , Proteínas Potenciadoras de Unión a CCAAT/metabolismo , Puntos de Control del Ciclo Celular/efectos de los fármacos , Puntos de Control del Ciclo Celular/genética , Proliferación Celular/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Técnicas de Silenciamiento del Gen , Humanos , Mesilato de Imatinib/farmacología , Células K562 , MicroARNs/genética , ARN Largo no Codificante/genética , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/genéticaRESUMEN
Light is an important source of energy as well as environmental signal for the regulation of biosynthesis and accumulation of multiple secondary metabolites in plants. Polyphenols are the major class of secondary metabolites in tea, which possess potential antioxidant properties. In order to investigate the effect of light signal on the regulation of biosynthesis and accumulation of polyphenols in tea seedlings, a low-intensity white light was used and the change in trends of polyphenol contents, patterns of gene expression, and corresponding enzymatic activities were studied. LC-TOF/MS analysis revealed that light signal promoted the accumulation of hydroxycinnamic acid derivatives and nongalloylated catechin (EGC), while it restrained the accumulation of ß-glucogallin and galloylated catechins. The quantitative reverse transcription-PCR analysis showed that the expression levels of the regulator genes and some structural genes involved in photomorphogenesis and biosynthetic pathway of nongalloylated catechins, respectively, were up-regulated. In contrast, the expression of DHD/SDH and UGT genes, which may be involved in biosynthetic pathway of ßG, was down-regulated. The corresponding in vitro enzyme assays revealed decrease in the activity of ECGT (galloylates nongalloylated catechins) and an increase in activity of GCH (hydrolyzes galloylated catechins) during de-etiolation. The present study yielded inconsistent accumulation patterns of phenolic acids, flavan-3-ols, and flavonols in tea seedlings during de-etiolation. In addition, the accumulation of catechins was possibly jointly influenced by the biosynthesis, hydrolysis, glycosylation, and galloylation of polyphenols in tea plants.
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Luz , Polifenoles/metabolismo , Plantones/metabolismo , Plantones/efectos de la radiación , Té/metabolismo , Té/efectos de la radiación , Etiolado/efectos de la radiaciónRESUMEN
Catechins (flavan-3-ols), the most important secondary metabolites in the tea plant, have positive effects on human health and are crucial in defense against pathogens of the tea plant. The aim of this study was to elucidate the biosynthetic pathway of galloylated catechins in the tea plant. The results suggested that galloylated catechins were biosynthesized via 1-O-glucose ester-dependent two-step reactions by acyltransferases, which involved two enzymes, UDP-glucose:galloyl-1-O-ß-D-glucosyltransferase (UGGT) and a newly discovered enzyme, epicatechin:1-O-galloyl-ß-D-glucose O-galloyltransferase (ECGT). In the first reaction, the galloylated acyl donor ß-glucogallin was biosynthesized by UGGT from gallic acid and uridine diphosphate glucose. In the second reaction, galloylated catechins were produced by ECGT catalysis from ß-glucogallin and 2,3-cis-flavan-3-ol. 2,3-cis-Flavan-3-ol and 1-O-galloyl-ß-D-glucose were appropriate substrates of ECGT rather than 2,3-trans-flavan-3-ol and 1,2,3,4,6-pentagalloylglucose. Purification by more than 1641-fold to apparent homogeneity yielded ECGT with an estimated molecular mass of 241 to 121 kDa by gel filtration. Enzyme activity and SDS-PAGE analysis indicated that the native ECGT might be a dimer, trimer, or tetramer of 60- and/or 58-kDa monomers, and these monomers represent a heterodimer consisting of pairs of 36- or 34- of and 28-kDa subunits. MALDI-TOF-TOF MS showed that the protein SCPL1199 was identified. Epigallocatechin and epicatechin exhibited higher substrate affinities than ß-glucogallin. ECGT had an optimum temperature of 30 °C and maximal reaction rates between pH 4.0 and 6.0. The enzyme reaction was inhibited dramatically by phenylmethylsulfonyl fluoride, HgCl(2), and sodium deoxycholate.
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Camellia sinensis/enzimología , Catequina/metabolismo , Ácido Gálico/metabolismo , Proteínas de Plantas/aislamiento & purificación , Proteínas de Plantas/metabolismo , Transferasas/aislamiento & purificación , Transferasas/metabolismo , Camellia sinensis/química , Camellia sinensis/genética , Estabilidad de Enzimas , Cinética , Proteínas de Plantas/química , Proteínas de Plantas/genética , Transferasas/química , Transferasas/genéticaRESUMEN
BACKGROUND: Technetium-99m or (99m)Tc is widely used for labeling peptide in nuclear medicine. Somatostatin and its analog can inhibit tumor cell growth after binding with its receptor. This research was to study the preclinical effect of a new (99m)Tc-6-hydrazinopyridine-3-carboxylic acid (HYNIC)-depreotide, indirect (99m)Tc labeling of depreotide using HYNIC as a bifunctional chelator. METHODS: The cyclopeptide, cyclo-[(N-Me) Phe-Tyr-D-Trp-Lys-Val-Hcy], the linear peptide, and [ClCH(2)-CO×b-Dap-Lys- Cys-Lys×amide] were synthesized by Fmoc solid-phase synthesis. The cyclopeptide and the linear peptide were linked by liquid-phase synthesis. The product depreotide was isolated and purified by high performance liquid chromatography and was confirmed by mass spectrography. Depreotide was labeled with (99m)Tc through a direct labeling method, using HYNIC as a bifunctional chelator. Paper chromatography method was used to calculate the labeling rate, and through the comparative analysis selected the best mark conditions. The new (99m)Tc-HYNIC-depreotide was tested by high-performance liquid chromatography (HPLC). The internalization and externalization rates of the new (99m)Tc-HYNIC-depreotide were studied in A549 cells. Furthermore, biodistribution of the radiopeptide was studied in nude mice, bearing tumors from human lung carcinoma cells SPC-A1. RESULTS: The molecular of synthesize depreotide was 1358, and the purity of it was 95.29%. The labeling efficiency of (99m)Tc-HYNIC-depreotide was highest at pH 6.0 and 15°C, about (70.95 ± 0.84)%. The labeling rate of the new (99m)Tc-HYNIC-depreotide rose to a peak of (20.75 ± 0.48)% at 60 minutes in A549 cells at 37°C and decreased slightly later, while it elevated gradually during the time course at 4°C and 25°C. The internalization rate of the new (99m)Tc-HYNIC-depreotide at 37°C increased gradually and reached the peak of 84.4% in 120 minutes, while the externalization rate of the new (99m)Tc-HYNIC-depreotide was always less than 20%. In mice bearing the experimental SPC-A1 tumor, the new (99m)Tc-HYNIC-depreotide demonstrated a high tumor uptake of (4.05 ± 0.04)% ID/g at 1.5 hpi and remained high ((2.51 ± 0.06)% ID/g) at 4 hpi. The tumor-to-lung activity concentration ratio (T/Lu) was very high for the new (99m)Tc-HYNIC-depreotide at all time points. So did the tumor-to-muscle activity (T/Mu) and tumor-to-blood activity concentration ratios (T/Bl). CONCLUSION: The findings suggested that the new (99m)Tc-HYNIC-depreotide might be a promising candidate radiopharmaceutical for imaging somatostatin receptor positive lung cancer.