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Organophosphorus magnetic molecularly imprinted polymers (OMMIPs) with high adsorption capacities (13.5-83.8 mg g-1) and good applicability were developed for efficient extraction and pre-concentration of multiple organophosphorus pesticides (OPPs) from foodstuffs. The OMMIP-based sample pretreatment coupled with low-temperature plasma ambient ionization mass spectrometry achieved rapid screening for 90 kinds of pesticides at default maximum residue limits of National Standard (GB 2763-2021) in nine types of agro-products. The OMMIP-based liquid chromatography coupled with triple quadrupole mass spectroscopy assay demonstrated rapid magneto-actuated isolation, efficient removal of matrix interference, and reduced signal suppression, resulting in a short detection time (30 min), compliant recoveries (60.1-127.5%), low detection limits (0.0001-0.073 µg g-1), and simultaneous quantification of multi-pesticides. The yolk-shell-structured OMMIPs (Fe3O4@mTiO2@MIPs) demonstrated additional benefits of excellent ultraviolet light-driven catalytic degradation activity toward OPPs, making them eco-friendly for self-cleaning regeneration and reducing laboratory pesticide discharge. This work highlights the potential of OMMIPs for high-throughput and in situ pesticide monitoring in modern large-scale agricultural markets.
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PF-543 is a sphingosine kinase 1ï¼SPHK1ï¼inhibitor developed by Pfizer and is currently considered the most potent selective SPHK1 inhibitor. SPHK1 catalyses the production of sphingosine 1-phosphate (S1P) from sphingosine. It is the rate-limiting enzyme of S1P production, and there is substantial evidence to support a very important role for sphingosine kinase in health and disease. This review is the first to summarize the role and mechanisms of PF-543 as an SPHK1 inhibitor in anticancer, antifibrotic, and anti-inflammatory processes, providing new therapeutic leads and ideas for future research and clinical trials.
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Idiopathic pulmonary fibrosis (IPF) is a debilitating condition, with a life expectancy of 2 to 5 years after diagnosis. Pirfenidone is a drug that has been shown to reduce the decline in forced vital capacity (FVC). We sought to identify whether different patterns on high-resolution computed tomography (HRCT) have different clinical effects through a retrospective comparison of baseline values and changes in pulmonary function tests (PFTs) after treatment with pirfenidone. We retrospectively analyzed data from IPF patients treated with pirfenidone at Nanjing Drum Tower Hospital in Jiangsu Province, China. According to the HRCT pattern, the patients were divided into usual interstitial pneumonitis (UIP) and possible UIP groups. Baseline clinical characteristics and changes every 6 months in the PFTs during the follow-up period were compared between the 2 groups. A total of 65 consecutive patients were enrolled. According to the HRCT pattern, patients were clustered into the UIP group (nâ =â 46) and possible UIP group (nâ =â 19). No difference was observed in the baseline PFTs ratio between the 2 groups. The FVC values of the 2 groups were not significantly different at the initial treatment and at 6 and 12 months after pirfenidone treatment (Pâ =â .081, 0.099, and 0.236, respectively). The improvement in % diffusion capacity of the lung for carbon monoxide (%DLCO) was higher in the possible UIP group after 6 and 12 months of pirfenidone treatment (Pâ =â .149, 0.026, and 0.025, respectively). The annual decrease in FVC was not significantly different between the 2 groups, and the annual decrease in %DLCO in the UIP group was significantly higher than that in patients with the possible UIP type (-7.767â ±â 12.797 vs 0.342â ±â 20.358, Pâ <â .05). These results indicate that patients with IPF with a possible UIP pattern on HRCT showed indications of a good response to pirfenidone.
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Fibrose Pulmonar Idiopática , Humanos , Estudos Retrospectivos , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Fibrose Pulmonar Idiopática/tratamento farmacológico , Pulmão/diagnóstico por imagem , Piridonas/uso terapêutico , Tomografia Computadorizada por Raios X/métodosRESUMO
Long-wavelength broadband near-infrared (NIR) phosphors have attracted considerable interest in the fields of medical cosmetology and organic detection because of their special emission band. Herein, Ca2GeO4(CGO): Cr4+ NIR phosphor, presenting a broadband emission with longer wavelength ranging from 1100 to 1600 nm, has been synthesized. Further, the luminescence intensity and quantum efficiency of Cr4+ could be obviously improved via the energy transfer from Eu3+ to Cr4+. The energy transfer is dominated by the dipole-dipole mechanism, which can be inferred from the spectra and the decay curves. Furthermore, in order to evaluate the potential application, an NIR phosphor-converted light-emitting diode (pc-LED) based on blue chip has been prepared. Consequently, CGO: Eu3+, Cr4+ exhibits proper output power and wider half-width than the NIR LED chip, indicating its great prospect for long-wavelength NIR pc-LED applications.
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Many factors are responsible for the diminished quality of shrimp during cold storage, while the role of collagen has rarely been studied. This study therefore investigated the relationship between collagen degradation and changes of textural properties of Pacific white shrimp, and its hydrolysis by endogenous proteinases. The textural properties of shrimp decreased gradually along with disruption of shrimp muscle tissues, and the chewiness property of shrimp muscle showed a linear relationship with collagen contents in muscle during 6-day-storage at 4 °C. Pepsin-solubilized collagen in shrimp muscle consisted of one α1 chain and two α2 chains, revealing a typical tripeptide sequence (i.e., Gly-X-Y) in their molecules. In addition, collagen could be hydrolyzed by crude endogenous proteinases extracted from shrimp hepatopancreas, and serine proteinase plays a critical role in the process. These findings strongly suggested that the quality reduction of shrimp during cold storage is closely associated with collagen degradation.
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Penaeidae , Peptídeo Hidrolases , Animais , Crustáceos , Hepatopâncreas/metabolismo , Penaeidae/química , Peptídeo Hidrolases/metabolismo , Alimentos Marinhos , Armazenamento de Alimentos , Temperatura BaixaRESUMO
Lithium metal anodes possess ultrahigh theoretical specific capacity for next-generation lithium metal batteries, but the infinite volume expansion and the growth of lithium dendrites remain a huge obstacle to their commercialization. Therefore, here, we construct a CuO-loaded 3D polyethersulfone (PES) nanofiber frame onto a lithiophilic Cu2O/Cu substrate to promote the lithium storage performance of the composite anode, and the 3D frame can effectively alleviate the volume expansion of lithium (Li) metal anodes. Meanwhile, lithium reacts with CuO in the composite nanofiber and Cu2O of the substrate to generate Li2O, which can strengthen the solid electrolyte interface (SEI) layer and achieve the uniform deposition of lithium. In addition, the combination of the heat treatment method and electrospinning technology solves the problem of poor adhesion between the fiber film and the substrate. As a result, the PES/CuO-Cu2O (PCC) composite current collector still maintains a smooth and flat lithium-depositing layer at 5 mA cm-2. The PCC-assembled Li||Cu half-cell can operate stably for 320 cycles at 0.5 mA cm-2, which is about 4 times that of bare Cu. Furthermore, symmetrical batteries with PCC@Li can maintain excellent cycle stability for 1770 h. Accordingly, this work provides a low-cost and highly effective strategy for stabilizing the lithium metal anode.
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BACKGROUND: High blood pressure, anxiety, depression and sleep disorder is very common in patients with hypertension. We aimed to perform a meta-analysis to evaluate the effects of adjuvant music therapy for patients with hypertension, to provide insights to the clinical management of hypertension. METHODS: Two authors searched PubMed, Embase, Web of Science, the Cochrane Library, Chinese National Knowledge Infrastructure, China Biomedical Literature Database, Wanfang Databases for randomized controlled trials (RCTs) on the role of music therapy in hypertension up to Oct 15, 2022. RevMan 5.3 software was used for meta-analysis. RESULTS: A total of 20 RCTs including 2306 patients were finally included. 1154 patients received music therapy. Meta-analysis showed that music therapy can effectively reduce the systolic blood pressure(MD = - 9.00, 95%CI: - 11.99~- 6.00), diastolic blood pressure(MD = -6.53, 95%CI: -9.12~- 3.93), heart rate (MD = -3.76, 95%CI: -7.32~- 0.20), self-rating anxiety scale (SAS) score(MD =-8.55, 95%CI: -12.04~-4.12), self-rating depression scale (SDS) score(MD = -9.17, 95%CI: -13.85~-5.18), Hamilton anxiety scale (HAMA), score(MD = -3.37, 95%CI: - 5.38~- 1.36), PSQI score(MD =-1.61, 95%CI:-2.30~- 0.93) compared with routine therapy in patients with hypertension(all P < 0.05). No publication bias in the synthesized outcomes were found (all P > 0.05). CONCLUSION: Music therapy can effectively control blood pressure and heart rate, reduce anxiety and depression levels, and improve sleep quality in hypertensive patients. Limited by the quantity and quality of included studies, the above conclusions need to be verified by more high-quality studies.
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Hipertensão , Musicoterapia , Música , Humanos , Ansiedade/terapia , Pressão Sanguínea/fisiologia , Hipertensão/terapiaRESUMO
INTRODUCTION: The prognosis of anti-MDA5 antibody-positive dermatomyositis/clinically amyopathic dermatomyositis-associated interstitial lung disease (MDA5-DM/CADM-ILD) is poor. This study was to evaluate the effect of serum soluble CD206 (sCD206), a biomarker of macrophage activation, on predicting the interstitial lung disease (ILD) deterioration and prognosis for MDA5-DM/CADM-ILD. METHODS: Forty-one patients diagnosed with MDA5-DM/CADM-ILD were retrospectively included. The clinical data were analyzed. Serum sCD206 levels were measured in 41 patients and 30 healthy controls. The relation between sCD206 levels and ILD deterioration was assessed. Receiver operating characteristic (ROC) curve was generated to determine the optimal cut-off value of sCD206 for predicting outcome. The association between sCD206 and survival was examined. RESULTS: The median serum sCD206 level in patients was significantly higher than healthy controls (464.1 ng/mL vs. 349.1 ng/mL, P = 0.002). In DM/CADM patients, the sCD206 level was significantly higher in patients with acute/subacute interstitial lung disease (AILD/SILD) than those with chronic interstitial lung disease (CILD) (539.2 ng/mL vs. 309.4 ng/mL, P = 0.005). The AUC of sCD206 was 0.885 for predicting mortality (95% CI 0.779-0.990). Patients were divided into two groups: sCD206 high level group (≥400 ng/mL) and sCD206 low level group (<400 ng/mL). Patients with sCD206 high level had significantly decreased survival rate than those with low level (25% vs. 88%, P < 0.001). The adjusted hazard ratio of sCD206 for mortality was 1.003 (adjusted for age and gender, P < 0.001), with sCD206 high level associated with higher death risk (HR 4.857, P = 0.006). CONCLUSION: Serum sCD206 might be a potential predictor of ILD deterioration and prognosis for Chinese patients with MDA5-DM/CADM-ILD.
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d-(-)-Pantolactone (DPL) is a key intermediate for the production of d-(+)-pantothenate (vitamin B5). Deracemization of d,l-pantolactone (D,L-PL) through oxidizing l-(+)-pantolactone (LPL) to ketopantoyl lactone (KPL) and subsequently reducing KPL to DPL is a promising route for synthesizing DPL. Herein, a newly mined l-pantolactone dehydrogenase from Rhodococcus hoagie (RhoLPLDH) was used for the oxidative dehydrogenation of LPL. To alleviate inclusion bodies formed by membrane-bound RhoLPLDH intracellular expression in E. coli, strategies involving chaperone assistance and decreasing induction temperature were used to achieve RhoLPLDH soluble expression. To enhance its activity, directed evolution and hydrophilicity-based engineering yielded increased catalytic activity and thermostability. 1 M LPL was efficiently converted to KPL by engineering strain CM5 co-expressing RhoLPLDHL254I/V241I/I156L/F224Q/N164K and chaperone. A "two stages in one-pot" method was employed in deracemization of 1 M D,L-PL with 91.2% yield. These results demonstrated that CM5 catalyst exhibits great potential in enzyme cascade deracemization for the production of DPL.
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4-Butirolactona , Escherichia coli , Escherichia coli/genética , Escherichia coli/metabolismo , Catálise , 4-Butirolactona/metabolismo , Oxirredutases/metabolismoRESUMO
The intestine is a site of immune cell priming at birth. Therefore, spatial transcriptomes were performed to define how the transcriptomic landscape was spatially organized in the posterior intestine of Sebastes schlegelii following Edwardsiella piscicida infection. In the healthy condition, we identified a previously unappreciated molecular regionalization of the posterior intestine. Following bacterial infection, most immune-related genes were identified in mucosa layer. Moreover, investigation of immune-related genes and genes in immune-related KEGG pathways based on spatial transcriptomes shed light on which sections of these genes are in the posterior intestine. Meanwhile, the high expression of genes related to regeneration also indicated that the posterior intestine was responding to the invasion of pathogens by constantly proliferating new cells. In addition, the increasing microbiota communities indicated that these bacteria maintained posterior intestine integrity and shaped the mucosal immune system. Taken together, spatial transcriptomes and microbiota compositions have significant implications for understanding the immune mechanism that responds to E. piscicida infection in the posterior intestine of S. schlegelii, which also provides a theoretical basis for the spatial distribution of immune genes and changes in bacterial flora in other teleosts in the process of resisting pathogens.
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Microbiota , Perciformes , Animais , Transcriptoma , Intestinos , Perfilação da Expressão GênicaRESUMO
Tropical forests are biologically diverse and structurally complex ecosystems that can store a large quantity of carbon and support a great variety of plant and animal species. However, tropical forest structure can vary dramatically within seemingly homogeneous landscapes due to subtle changes in topography, soil fertility, species composition and past disturbances. Although numerous studies have reported the effects of field-based stand structure attributes on aboveground biomass (AGB) in tropical forests, the relative effects and contributions of UAV LiDAR-based canopy structure and ground-based stand structural attributes in shaping AGB remain unclear. Here, we hypothesize that mean top-of-canopy height (TCH) enhances AGB directly and indirectly via species richness and horizontal stand structural attributes, but these positive relationships are stronger at a larger spatial scale. We used a combined approach of field inventory and LiDAR-based remote sensing to explore how stand structural attributes (stem abundance, size variation and TCH) and tree species richness affect AGB along an elevational gradient in tropical forests at two spatial scales, i.e., 20 m × 20 m (small scale), and 50 m × 50 m (large scale) in southwest China. Specifically, we used structural equation models to test the proposed hypothesis. We found that TCH, stem size variation and abundance were strongly positively associated with AGB at both spatial scales, in addition to which increasing TCH led to greater AGB indirectly through increased stem size variation. Species richness had negative to negligible influences on AGB, but species richness increased with increasing stem abundance at both spatial scales. Our results suggest that light capture and use, modulated by stand structure, are key to promoting high AGB stocks in tropical forests. Thus, we argue that both horizontal and vertical stand structures are important for shaping AGB, but the relative contributions vary across spatial scales in tropical forests. Importantly, our results highlight the importance of including vertical forest stand attributes for predicting AGB and carbon sequestration that underpins human wellbeing.
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For the coastal aquifers, recent research have shown that the tidal has a significant effect on saltwater intrusion in the near-shore aquifer. However, it is currently unclear how the tidal river contributes to the groundwater flow and salinity distribution in the upstream aquifer of the estuary. This study examined the effects of a tidal river on the dynamic characteristics of groundwater flow and salt transport in a tidal river-coastal aquifer system using field monitoring data and numerical simulations. It was found that changes in tidal-river level led to the reversal of groundwater flow. For a tidal cycle, the maximum area of seawater intrusion is about 41.16 km2 at the end of the high tide stage. Then the area gradually decreased to 39.02 km2 at the end of the low tide stage. More than 2 km2 area variation can be observed in a tidal cycle. Compared to the low tide stage, the area of SWI increased by 5 % at high tide stage. The SWI region was also spreading landward from the tidal river. In addition, we quantified the water exchange and salt flux between the tidal river and aquifer. When the tidal fell below the level of the riverbed, the water exchange rate was stabilized at about -1.6 m/h. The negative value indicated that the river was recharged by the groundwater. With the increasing of tidal water level, the water exchange rate gradually changes from negative to positive and reached the maximum value of 3.2 m/h at the beginning of the falling tide stage. The presence of a physical river dam can amplify the difference in water level between high and low tides, thereby enhancing the influence of a tidal river on water exchange and salt flux. The findings lay the foundation for gaining a comprehensive understanding of the tidal river on groundwater flow and salt transport in upstream aquifers.
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Factors shaping the interspecific variations in herbivory have puzzled ecologists for decades and several hypotheses have been proposed to explain interspecific variation in leaf herbivory. In a tropical rainforest in Yunnan Province, China, we collected 6732 leaves from 129 species with canopy heights ranging from 1.6 to 65.0 m above the ground. We tested the role of canopy height, the diversity, composition and structural heterogeneity of neighbors and leaf traits in shaping the interspecific variations in herbivory. Results show that leaf herbivory decreased with canopy height and specific leaf area (SLA) and increased with leaf size. However, neighboring species' diversity, composition, and structural heterogeneity showed no association with herbivory. Therefore, neither the visual apparency effect nor the associational resistance effect was detected in this hyperdiverse tropical rainforest. These findings highlight the importance of vertical structure in shaping herbivory patterns in natural communities.
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Herbivoria , Árvores , Floresta Úmida , China , Folhas de Planta/química , Características da VizinhançaRESUMO
6-O-[18F]Fluoroethylerlotinib (6-O-[18F]FEE), with a suitable half-life for commercial distribution, may be a good replacement for [11C]erlotinib to identify epidermal growth factor receptor (EGFR) positive tumors with activating mutations to tyrosine kinase inhibitors therapy. In this study, we explored the fully automated synthesis of 6-O-[18F]FEE and investigated its pharmacokinetics in tumor-bearing mice. 6-O-[18F]FEE with high specific activity (28-100 GBq/µmol) and radiochemistry purity (over 99 %) was obtained by two-step reaction and Radio-HPLC separation in PET-MF-2 V-IT-1 automated synthesizer. PET imaging of 6-O-[18F]FEE in HCC827, A431, and U87 tumor-bearing mice with different EGFR expression and mutation was performed. Uptake and blocking of PET imaging indicated that the probe specifically targeted exon 19 deleted EGFR (the quantitative analysis of tumor-to-mouse ratio for HCC827, HCC827 blocking, U87, A431 was 2.58 ± 0.24, 1.20 ± 0.15, 1.18 ± 0.19, and 1.05 ± 0.13 respectively). Dynamic imaging was used to study the pharmacokinetics of the probe in tumor-bearing mice. Logan plot graphical analysis demonstrated late linearity and a high fitting correlation coefficient (0.998), supporting reversible kinetics. According to the Akaike Information Criterion (AIC) rule, the 2-compartment reversible model was more consistent with the metabolic properties of 6-O-[18F]FEE. The automated radiosynthesis and pharmacokinetic analysis will promote clinically transformation of 6-O-[18F]FEE.
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Neoplasias Pulmonares , Tomografia por Emissão de Pósitrons , Animais , Camundongos , Cloridrato de Erlotinib , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , Receptores ErbB , Mutação , Linhagem Celular TumoralRESUMO
Since the discovery of fluorescent proteins (FPs), their rich fluorescence spectra and photochemical properties have promoted widespread biological research applications. FPs can be classified into green fluorescent protein (GFP) and its derivates, red fluorescent protein (RFP) and its derivates, and near-infrared FPs. With the continuous development of FPs, antibodies targeting FPs have emerged. The antibody, a class of immunoglobulin, is the main component of humoral immunity that explicitly recognizes and binds antigens. Monoclonal antibody, originating from a single B cell, has been widely applied in immunoassay, in vitro diagnostics, and drug development. The nanobody is a new type of antibody entirely composed of the variable domain of a heavy-chain antibody. Compared with conventional antibodies, these small and stable nanobodies can be expressed and functional in living cells. In addition, they can easily access grooves, seams, or hidden antigenic epitopes on the surface of the target. This review provides an overview of various FPs, the research progress of their antibodies, particularly nanobodies, and advanced applications of nanobodies targeting FPs. This review will be helpful for further research on nanobodies targeting FPs, making FPs more valuable in biological research.
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Anticorpos de Domínio Único , Anticorpos Monoclonais , Proteínas de Fluorescência Verde/metabolismo , Antígenos , Cadeias Pesadas de Imunoglobulinas/químicaRESUMO
Introduction: Kidney stone disease (KS) is a complicated disease with an increasing global incidence. It was shown that Bushen Huashi decoction (BSHS) is a classic Chinese medicine formula that has therapeutic benefits for patients with KS. However, its pharmacological profile and mechanism of action are yet to be elucidated. Methods: The present study used a network pharmacology approach to characterize the mechanism by which BSHS affects KS. Compounds were retrieved from corresponding databases, and active compounds were selected based on their oral bioavailability (≥30) and drug-likeness index (≥0.18). BSHS potential proteins were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, whereas KS potential genes were obtained from GeneCards and OMIM, TTD, and DisGeNET. Gene ontology and pathway enrichment analysis were used to determine potential pathways associated with genes. The ingredients of BSHS extract were identified by the ultra-high-performance liquid chromatography coupled with quadrupole orbitrap mass spectrometry (UHPLC-Q/Orbitrap MS). The network pharmacology analyses predicted the potential underlying action mechanisms of BSHS on KS, which were further validated experimentally in the rat model of calcium oxalate kidney stones. Results: Our study found that BSHS reduced renal crystal deposition and improved renal function in ethylene glycol(EG)+ammonium chloride(AC)-induced rats, and also reversed oxidative stress levels and inhibited renal tubular epithelial cell apoptosis in rats. BSHS upregulated protein and mRNA expression of E2, ESR1, ESR2, BCL2, NRF2, and HO-1 in EG+AC-induced rat kidney while downregulating BAX protein and mRNA expression, consistent with the network pharmacology results. Discussion: This study provides evidence that BSHS plays a critical role in anti-KS via regulation of E2/ESR1/2, NRF2/HO-1, and BCL2/BAX signaling pathways, indicating that BSHS is a candidate herbal drug for further investigation in treating KS.
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Cálculos Renais , Farmacologia em Rede , Animais , Ratos , Fator 2 Relacionado a NF-E2/genética , Cálculos Renais/tratamento farmacológico , Proteínas Proto-Oncogênicas c-bcl-2 , RNA MensageiroRESUMO
Sustainable development goals (SDGs) in the United Nations 2030 Agenda call for action by all nations to promote economic prosperity while protecting the planet. Projection of future land-use change under SDG scenarios is a new attempt to scientifically achieve the SDGs. Herein, we proposed four scenario assumptions based on the SDGs, including the sustainable economy (ECO), sustainable grain (GRA), sustainable environment (ENV), and reference (REF) scenarios. We forecasted land-use change along the Silk Road (resolution: 300 m) and compared the impacts of urban expansion and forest conversion on terrestrial carbon pools. There were significant differences in future land use change and carbon stocks, under the four SDG scenarios, by 2030. In the ENV scenario, the trend of decreasing forest land was mitigated, and forest carbon stocks in China increased by approximately 0.60% compared to 2020. In the GRA scenario, the decreasing rate of cultivated land area has slowed down. Cultivated land area in South and Southeast Asia only shows an increasing trend in the GRA scenario, while it shows a decreasing trend in other SDG scenarios. The ECO scenario showed highest carbon losses associated with increased urban expansion. The study enhances our understanding of how SDGs can contribute to mitigate future environmental degradation via accurate simulations that can be applied on a global scale.
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Excellent through-plane thermally conductive composites are highly demanded for efficient heat dissipation. Giant sheets have large crystalline domain and significantly reduce interface phonon scattering, making them promising to build highly thermally conductive composites. However, realizing vertical orientation of giant sheets remains challenging due to their enormous mass and huge hydrodynamic drag force. Here, we achieve highly vertically ordered liquid crystals of giant graphite oxide (more than 100 µm in lateral dimension) by microwire shearing, which endows the composite with a recorded through-plane thermal conductivity of 94 W m-1 K-1 . Microscale shearing fields induced by vertical motion of microwires conquer huge hydrodynamic energy barrier and vertically reorient giant sheets. The resulting liquid crystals exhibit extremely retarded relaxation and impart large-scale vertical array with bidirectional ordering degree as high as 0.82. The graphite array-based composites demonstrate an ultrahigh thermal enhancement efficiency of over 35 times per unit volume. Furthermore, the composites improve cooling efficiency by 93% for thermal management tests compared to commercial thermal interface materials. This work offers a novel methodology to precisely manipulate the orientation of giant particles and promote large-scale fabrication of vertical array with advanced functionalities.
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Tributyltin chloride (TBTCL), a commonly used antiseptic substance, is commonly found in the environment. Human exposure to TBTCL through the consumption of contaminated seafood, fish, or drinking water has aroused concern. It is well-characterized that TBTCL has multiple detrimental effects on the male reproductive system. However, the potential cellular mechanisms are not fully elucidated. Here, we characterized molecular mechanisms of TBTCL-induced cell injury in Leydig cells, a critical supporter for spermatogenesis. We showed that TBTCL induces apoptosis and cell cycle arrest in TM3 mouse Leydig cells. RNA sequencing analyses revealed that endoplasmic reticulum (ER) stress and autophagy were potentially involved in TBTCL-induced cytotoxicity. We further showed that TBTCL causes ER stress and inhibited autophagy flux. Notably, the inhibition of ER stress attenuates not only TBTCL-induces autophagy flux inhibition but also apoptosis and cell cycle arrest. Meanwhile, the activation of autophagy alleviates, and inhibition of autophagy exaggerates TBTCL-induced apoptosis and cell cycle arrest flux. These results suggest that TBTCL-induced ER stress and autophagy flux inhibition contributed to apoptosis and cell cycle arrest in Leydig cells, providing novel understanding into the mechanisms of TBTCL-induced testis toxicity.
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Autofagia , Células Intersticiais do Testículo , Animais , Humanos , Camundongos , Masculino , Testículo , Estresse do Retículo EndoplasmáticoRESUMO
Introduction: Identifying spatial patterns of biodiversity along elevational gradients provides a unified framework for understanding these patterns and predicting ecological responses to climate change. Moreover, microorganisms and plants are closely interconnected (e.g., via the rhizosphere) and thus may share spatial patterns of diversity and show similar relationships with environments. Methods: This study compared diversity patterns and relationships with environments in host plants and rhizosphere microorganisms (including various functional groups) along elevational gradients across three climatic zones. Results: We found that above-and belowground diversity decreased monotonically or showed a hump-shaped or U-shaped pattern along elevation gradients. However, the diversity patterns of plants, bacteria, and fungi varied depending on the taxon and climatic zone. Temperature and humidity strongly contribute to above-and belowground diversity patterns and community composition along elevational gradients. Nonetheless, soil factors might be important regulators of diversity patterns and the community composition of plants and microorganisms along these gradients. Structural equation modeling revealed that environmental factors had a stronger direct effect on rhizosphere microbial diversity than host plant diversity. Discussion: In sum, spatial patterns of diversity and their relationships with environments in rhizosphere microorganisms and their host plants differed at the regional scale. Different functional groups (e.g., pathogen, mycorrhiza and nitrifier) of soil microorganisms may have divergent elevational patterns and environmental responses. These data improve our understanding of elevational diversity patterns, and provide new insights into the conservation of biodiversity and ecosystem management, especially under climate change.