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Trace-amine-associated receptors (TAARs), a group of biogenic amine receptors, have essential roles in neurological and metabolic homeostasis1. They recognize diverse endogenous trace amines and subsequently activate a range of G-protein-subtype signalling pathways2,3. Notably, TAAR1 has emerged as a promising therapeutic target for treating psychiatric disorders4,5. However, the molecular mechanisms underlying its ability to recognize different ligands remain largely unclear. Here we present nine cryo-electron microscopy structures, with eight showing human and mouse TAAR1 in a complex with an array of ligands, including the endogenous 3-iodothyronamine, two antipsychotic agents, the psychoactive drug amphetamine and two identified catecholamine agonists, and one showing 5-HT1AR in a complex with an antipsychotic agent. These structures reveal a rigid consensus binding motif in TAAR1 that binds to endogenous trace amine stimuli and two extended binding pockets that accommodate diverse chemotypes. Combined with mutational analysis, functional assays and molecular dynamic simulations, we elucidate the structural basis of drug polypharmacology and identify the species-specific differences between human and mouse TAAR1. Our study provides insights into the mechanism of ligand recognition and G-protein selectivity by TAAR1, which may help in the discovery of ligands or therapeutic strategies for neurological and metabolic disorders.
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Proteínas de Ligação ao GTP , Receptores Acoplados a Proteínas G , Animais , Humanos , Camundongos , Aminas/metabolismo , Anfetamina/metabolismo , Antipsicóticos/química , Antipsicóticos/metabolismo , Sítios de Ligação , Catecolaminas/agonistas , Catecolaminas/química , Catecolaminas/metabolismo , Microscopia Crioeletrônica , Proteínas de Ligação ao GTP/química , Proteínas de Ligação ao GTP/metabolismo , Proteínas de Ligação ao GTP/ultraestrutura , Ligantes , Simulação de Dinâmica Molecular , Mutação , Polifarmacologia , Receptores Acoplados a Proteínas G/química , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/ultraestrutura , Especificidade da Espécie , Especificidade por SubstratoRESUMO
Transforming smallholder farms is critical to global food security and environmental sustainability. The science and technology backyard (STB) platform has proved to be a viable approach in China. However, STB has traditionally focused on empowering smallholder farmers by transferring knowledge, and wide-scale adoption of more sustainable practices and technologies remains a challenge. Here, we report on a long-term project focused on technology scale-up for smallholder farmers by expanding and upgrading the original STB platform (STB 2.0). We created a formalized and standardized process by which to engage and collaborate with farmers, including integrating their feedback via equal dialogues in the process of designing and promoting technologies. Based on 288 site-year of field trials in three regions in the North China Plain over 5 y, we find that technologies cocreated through this process were more easily accepted by farmers and increased their crop yields and nitrogen factor productivity by 7.2% and 28.1% in wheat production and by 11.4% and 27.0% in maize production, respectively. In promoting these technologies more broadly, we created a "one-stop" multistakeholder program involving local government agencies, enterprises, universities, and farmers. The program was shown to be much more effective than the traditional extension methods applied at the STB, yielding substantial environmental and economic benefits. Our study contributes an important case study for technology scale-up for smallholder agriculture. The STB 2.0 platform being explored emphasizes equal dialogue with farmers, multistakeholder collaboration, and long-term investment. These lessons may provide value for the global smallholder research and practitioners.
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Agricultura , China , Agricultura/métodos , Fazendeiros , Humanos , Produtos Agrícolas/crescimento & desenvolvimento , Comportamento Cooperativo , Zea mays/crescimento & desenvolvimento , Desenvolvimento Sustentável , Conservação dos Recursos Naturais/métodos , Triticum/crescimento & desenvolvimento , Produção Agrícola/métodosRESUMO
Diatoms are a group of phytoplankton that contribute disproportionately to global primary production. Traditional paradigms that suggest diatoms are consumed primarily by larger zooplankton are challenged by sporadic parasitic "epidemics" within diatom populations. However, our understanding of diatom parasitism is limited by difficulties in quantifying these interactions. Here, we observe the dynamics of Cryothecomonas aestivalis (a protist) infection of an important diatom on the Northeast U.S. Shelf (NES), Guinardia delicatula, with a combination of automated imaging-in-flow cytometry and a convolutional neural network image classifier. Application of the classifier to >1 billion images from a nearshore time series and >20 survey cruises across the broader NES reveals the spatiotemporal gradients and temperature dependence of G. delicatula abundance and infection dynamics. Suppression of parasitoid infection at temperatures <4 °C drives annual cycles in both G. delicatula infection and abundance, with an annual maximum in infection observed in the fall-winter preceding an annual maximum in host abundance in the winter-spring. This annual cycle likely varies spatially across the NES in response to variable annual cycles in water temperature. We show that infection remains suppressed for ~2 mo following cold periods, possibly due to temperature-induced local extinctions of the C. aestivalis strain(s) that infect G. delicatula. These findings have implications for predicting impacts of a warming NES surface ocean on G. delicatula abundance and infection dynamics and demonstrate the potential of automated plankton imaging and classification to quantify phytoplankton parasitism in nature across unprecedented spatiotemporal scales.
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Diatomáceas , Animais , Diatomáceas/fisiologia , Temperatura , Fitoplâncton , Eucariotos , ZooplânctonRESUMO
Hemoglobin (Hb) has been identified in at least 14 molluscan taxa so far. Research spanning over 130 years on molluscan Hbs focuses on their genes, protein structures, functions, and evolution. Molluscan Hbs are categorized into single-, two-, and multiple-domain chains, including red blood cell, gill, and extracellular Hbs, based on the number of globin domains and their respective locations. These Hbs exhibit variation in assembly, ranging from monomeric and dimeric to higher-order multimeric forms. Typically, molluscan Hbs display moderately high oxygen affinity, weak cooperativity, and varying pH sensitivity. Hb's potential role in antimicrobial pathways could augment the immune defense of bivalves, which may be a complement to their lack of adaptive immunity. The role of Hb as a respiratory protein in bivalves likely originated from the substitution of hemocyanin. Molluscan Hbs demonstrate adaptive evolution in response to environmental changes via various strategies (e.g. increasing Hb types, multimerization, and amino acid residue substitutions at key sites), enhancing or altering functional properties for habitat adaptation. Concurrently, an increase in Hb assembly diversity, coupled with a downward trend in oxygen affinity, is observed during molluscan differentiation and evolution. Hb in Protobranchia, Heteroconchia, and Pteriomorphia bivalves originated from separate ancestors, with Protobranchia inheriting a relative ancient molluscan Hb gene. In bivalves, extracellular Hbs share a common origin, while gill Hbs likely emerged from convergent evolution. In summary, research on molluscan Hbs offers valuable insights into the origins, biological variations, and adaptive evolution of animal Hbs.
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Hemoglobinas , Moluscos , Animais , Hemoglobinas/genética , Hemoglobinas/química , Hemoglobinas/metabolismo , Moluscos/genética , Moluscos/metabolismo , Oxigênio/metabolismoRESUMO
The receptor for colony stimulating factor 1 (CSF-1R) is important for the survival and function of myeloid cells that mediate pathology during experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). CSF-1 and IL-34, the ligands of CSF-1R, have similar bioactivities but distinct tissue and context-dependent expression patterns, suggesting that they have different roles. This could be the case in EAE, given that CSF-1 expression is up-regulated in the CNS, while IL-34 remains constitutively expressed. We found that targeting CSF-1 with neutralizing antibody halted ongoing EAE, with efficacy superior to CSF-1R inhibitor BLZ945, whereas IL-34 neutralization had no effect, suggesting that pathogenic myeloid cells were maintained by CSF-1. Both antiCSF-1 and BLZ945 treatment greatly reduced the number of monocyte-derived cells and microglia in the CNS. However, antiCSF-1 selectively depleted inflammatory microglia and monocytes in inflamed CNS areas, whereas BLZ945 depleted virtually all myeloid cells, including quiescent microglia, throughout the CNS. AntiCSF-1 treatment reduced the size of demyelinated lesions and microglial activation in the gray matter. Lastly, we found that bone marrowderived immune cells were the major mediators of CSF-1Rdependent pathology, while microglia played a lesser role. Our findings suggest that targeting CSF-1 could be effective in ameliorating MS pathology, while preserving the homeostatic functions of myeloid cells, thereby minimizing risks associated with ablation of CSF-1Rdependent cells.
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Encefalomielite Autoimune Experimental , Fator Estimulador de Colônias de Macrófagos , Esclerose Múltipla , Animais , Benzotiazóis/farmacologia , Benzotiazóis/uso terapêutico , Sistema Nervoso Central/imunologia , Encefalomielite Autoimune Experimental/tratamento farmacológico , Encefalomielite Autoimune Experimental/imunologia , Fator Estimulador de Colônias de Macrófagos/antagonistas & inibidores , Fator Estimulador de Colônias de Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/imunologia , Células Mieloides/efeitos dos fármacos , Células Mieloides/metabolismo , Ácidos Picolínicos/farmacologia , Ácidos Picolínicos/uso terapêutico , Receptor de Fator Estimulador de Colônias de Macrófagos/antagonistas & inibidoresRESUMO
Low-power and fast artificial neural network devices represent the direction in developing analogue neural networks. Here, an ultralow power consumption (0.8 fJ) and rapid (100 ns) La0.1Bi0.9FeO3/La0.7Sr0.3MnO3 ferroelectric tunnel junction artificial synapse has been developed to emulate the biological neural networks. The visual memory and forgetting functionalities have been emulated based on long-term potentiation and depression with good linearity. Moreover, with a single device, logical operations of "AND" and "OR" are implemented, and an artificial neural network was constructed with a recognition accuracy of 96%. Especially for noisy data sets, the recognition speed is faster after preprocessing by the device in the present work. This sets the stage for highly reliable and repeatable unsupervised learning.
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Raman spectroscopy has been widely used for label-free biomolecular analysis of cells and tissues for pathological diagnosis in vitro and in vivo. AI technology facilitates disease diagnosis based on Raman spectroscopy, including machine learning (PCA and SVM), manifold learning (UMAP), and deep learning (ResNet and AlexNet). However, it is not clear how to optimize the appropriate AI classification model for different types of Raman spectral data. Here, we selected five representative Raman spectral data sets, including endometrial carcinoma, hepatoma extracellular vesicles, bacteria, melanoma cell, diabetic skin, with different characteristics regarding sample size, spectral data size, Raman shift range, tissue sites, Kullback-Leibler (KL) divergence, and significant Raman shifts (i.e., wavenumbers with significant differences between groups), to explore the performance of different AI models (e.g., PCA-SVM, SVM, UMAP-SVM, ResNet or AlexNet). For data set of large spectral data size, Resnet performed better than PCA-SVM and UMAP. By building data characteristic-assisted AI classification model, we optimized the network parameters (e.g., principal components, activation function, and loss function) of AI model based on data size and KL divergence etc. The accuracy improved from 85.1 to 94.6% for endometrial carcinoma grading, from 77.1 to 90.7% for hepatoma extracellular vesicles detection, from 89.3 to 99.7% for melanoma cell detection, from 88.1 to 97.9% for bacterial identification, from 53.7 to 85.5% for diabetic skin screening, and mean time expense of 5 s.
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Análise Espectral Raman , Análise Espectral Raman/métodos , Humanos , Feminino , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/química , Aprendizado de Máquina , Melanoma/patologia , Melanoma/diagnóstico , Melanoma/classificação , Vesículas Extracelulares/química , Máquina de Vetores de Suporte , Bactérias/classificação , Bactérias/isolamento & purificação , Inteligência ArtificialRESUMO
Demyelination and failure of remyelination in the central nervous system (CNS) characterize a number of neurological disorders. Spontaneous remyelination in demyelinating diseases is limited, as oligodendrocyte precursor cells (OPCs), which are often present in demyelinated lesions in abundance, mostly fail to differentiate into oligodendrocytes, the myelinating cells in the CNS. In addition to OPCs, the lesions are assembled numbers of activated resident microglia/infiltrated macrophages; however, the mechanisms and potential role of interactions between the microglia/macrophages and OPCs are poorly understood. Here, we generated a transcriptional profile of exosomes from activated microglia, and found that miR-615-5p was elevated. miR-615-5p bound to 3'UTR of myelin regulator factor (MYRF), a crucial myelination transcription factor expressed in oligodendrocyte lineage cells. Mechanistically, exosomes from activated microglia transferred miR-615-5p to OPCs, which directly bound to MYRF and inhibited OPC maturation. Furthermore, an effect of AAV expressing miR-615-5p sponge in microglia was tested in experimental autoimmune encephalomyelitis (EAE) and cuprizone (CPZ)-induced demyelination model, the classical mouse models of multiple sclerosis. miR-615-5p sponge effectively alleviated disease progression and promoted remyelination. This study identifies miR-615-5p/MYRF as a new target for the therapy of demyelinating diseases.
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Encefalomielite Autoimune Experimental , Exossomos , MicroRNAs , Bainha de Mielina , Animais , Camundongos , Exossomos/metabolismo , Microglia/metabolismo , MicroRNAs/genéticaRESUMO
The search for high-performance and low-cost electrocatalysts in acid conditions still remains a challenging target. Herein, iridium (Ir) doped strontium manganate (named as Irx -SMO) is proposed as an efficient and durable low-iridium electrocatalyst for water oxidation in acidic media. The Ir0.1 -SMO with 75% less iridium in comparison to that of iridium dioxide (IrO2 ) exhibits excellent performance for oxygen evolution reaction (OER), which is even better than most of the iridium-based oxide electrocatalysts. The theoretical outcomes confirm the activation of the inert manganese sites in strontium manganate by the incorporation of iridium dopants. This work reveals the boosted effect of the iridium dopants on the OER activity of strontium manganate, providing a strategy to tune the activity of manganese-based perovskites in electrocatalysis.
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2D Ruddlesden-Popper phase layered perovskites (RPLPs) hold great promise for optoelectronic applications. In this study, a series of high-performance heterojunction phototransistors (HPTs) based on RPLPs with different organic spacer cations (namely butylammonium (BA+), cyclohexylammonium (CyHA+), phenethylammonium (PEA+), p-fluorophenylethylammonium (p-F-PEA+), and 2-thiophenethylammonium (2-ThEA+)) are fabricated successfully, in which high-mobility organic semiconductor 2,7-dioctyl[1]benzothieno[3,2-b]benzothiophene is adopted to form type II heterojunction channels with RPLPs. The 2-ThEA+-RPLP-based HPTs show the highest photosensitivity of 3.18 × 107 and the best detectivity of 9.00 × 1018 Jones, while the p-F-PEA+-RPLP-based ones exhibit the highest photoresponsivity of 5.51 × 106 A W-1 and external quantum efficiency of 1.32 × 109%, all of which are among the highest reported values to date. These heterojunction systems also mimicked several optically controllable fundamental characteristics of biological synapses, including excitatory postsynaptic current, paired-pulse facilitation, and the transition from short-term memory to long-term memory states. The device based on 2-ThEA+-RPLP film shows an ultra-high PPF index of 234%. Moreover, spacer engineering brought fine-tuned thin film microstructures and efficient charge transport/transfer, which contributes to the superior photodetection performance and synaptic functions of these RPLP-based HPTs. In-depth structure-property correlations between the organic spacer cations/RPLPs and thin film microstructure/device performance are systematically investigated.
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Conventional herbicide formulations suffer from serious problems such as easy drift, run-off and scouring into the environment, which pose enormous threats to human health and environmental safety. Herein, an innovative strategy is proposed to prepare oil-in-water nanoemulsions with long-term stability, enhanced droplet deposition, and improved nanoherbicide adhesion via steerable interfacial assembly of 1D amyloid-like protein nanocomposites. Bovine serum albumin (BSA) undergoes rapid amyloid-like aggregation upon reduction of its disulfide bond. The resulting phase-transitioned BSA (PTB) oligomers instantly self-assemble on the surface of cellulose nanofibers (CNF) to form the 1D PTB/CNF nanocomposites, which greatly expands the parameter space for interfacial assembly of amyloid-like proteins. The PTB/CNF nanocomposites exhibit excellent interfacial activity, enabling spontaneous adsorption at the oil-water interface to stabilize nanoemulsion. The excess PTB/CNF nanocomposites would also self-assemble at the air-aqueous interface upon spraying, resulting in efficient droplet deposition on (super)hydrophobic leaves. The deposited nanoherbicides show excellent resistance to wind/rain corrosion due to the robust amyloid-mediated adhesion, with a retention rate of more than 80% after severe scouring. Consequently, herbicide applications can be reduced by at least 30% compared to commercial emulsifiable concentrates, showing greater herbicidal efficiency. This study provides novel insights and approaches to promote sustainable agricultural development.
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Borophene, a promising material with potential applications in electronics, energy storage, and sensors, is successfully grown as a monolayer on Ag(111), Cu(111), and Au(111) surfaces using molecular beam epitaxy. The growth of two-dimensional borophene on Ag(111) and Au(111) is proposed to occur via surface adsorption and boron segregation, respectively. However, the growth mode of borophene on Cu(111) remains unclear. To elucidate this, scanning tunneling microscopy in conjunction with theoretical calculations is used to study the phase transformation of boron nanostructures under post-annealing treatments. Results show that by elevating the substrate temperature, boron nanostructures undergo an evolution from amorphous boron to striped-phase borophene (η = 1/6) adhering to the Cu ⟨ 1 1 ¯ 0 ⟩ $\langle {1\bar{1}0} \rangle $ step edge, and finally to irregularly shaped ß-type borophene (η = 5/36) either on the substrate surface or embedded in the topmost Cu layer. dI/dV spectra recorded near the borophene/Cu lateral interfaces indicate that the striped-phase borophene is a metastable phase, requiring more buckling and electron transfer to stabilize the crystal structure. These findings offer not only an in-depth comprehension of the ß-type borophene formation on Cu(111), but also hold potential for enabling borophene synthesis on weakly-binding semiconducting or insulating substrates with 1D active defects.
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BACKGROUND: Gastric cancer (GC) is one of the most prevalent malignant tumors worldwide and is associated with high morbidity and mortality rates. However, the specific biomarkers used to predict the postoperative prognosis of patients with gastric cancer remain unknown. Recent research has shown that the tumor microenvironment (TME) has an increasingly positive effect on anti-tumor activity. This study aims to build signatures to study the effect of certain genes on gastric cancer. METHODS: Expression profiles of 37 T cell-related genes and their TME characteristics were comprehensively analyzed. A risk signature was constructed and validated based on the screened T cell-related genes, and the roles of hub genes in GC were experimentally validated. RESULTS: A novel T cell-related gene signature was constructed based on CD5, ABCA8, SERPINE2, ESM1, SERPINA5, and NMU. The high-risk group indicated lower overall survival (OS), poorer immune efficacy, and higher drug resistance, with SERPINE2 promoting GC cell proliferation, according to experiments. SERPINE2 and CXCL12 were significantly correlated, indicating poor OS via the Youjiang cohort. CONCLUSIONS: This study identified T cell-related genes in patients with stomach adenocarcinoma (STAD) for prognosis estimation and proposed potential immunotherapeutic targets for STAD.
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Adenocarcinoma , Biomarcadores Tumorais , Neoplasias Gástricas , Microambiente Tumoral , Neoplasias Gástricas/genética , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/mortalidade , Humanos , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Adenocarcinoma/genética , Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Prognóstico , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Linfócitos T Reguladores/imunologia , Perfilação da Expressão Gênica , Masculino , FemininoRESUMO
BACKGROUND: VS-505 (AP301), an acacia and ferric oxyhydroxide polymer, is a novel fiber-iron-based phosphate binder. This two-part phase 2 study evaluated the tolerability, safety, and efficacy of oral VS-505 administered three times daily with meals in treating hyperphosphatemia in chronic kidney disease (CKD) patients receiving maintenance hemodialysis (MHD). METHODS: In Part 1, patients received dose-escalated treatment with VS-505 2.25, 4.50, and 9.00 g/day for 2 weeks each, guided by serum phosphorus levels. In Part 2, patients received randomized, open-label, fixed-dosage treatment with VS-505 (1.50, 2.25, 4.50, or 6.75 g/day) or sevelamer carbonate 4.80 g/day for 6 weeks. The primary efficacy endpoint was the change in serum phosphorus. RESULTS: The study enrolled 158 patients (Part 1: 25; Part 2: 133), with 130 exposed to VS-505 in total. VS-505 was well tolerated. The most common adverse events were gastrointestinal disorders, mainly feces discolored (56%) and diarrhea (15%; generally during weeks 1â2 of treatment). Most gastrointestinal disorders resolved without intervention, and none were serious. In Part 1, serum phosphorus significantly improved (mean change -2.0 mg/dL; 95% confidence interval -2.7, -1.4) after VS-505 dose escalation. In Part 2, serum phosphorus significantly and dose-dependently improved in all VS-505 arms, with clinically meaningful reductions with VS-505 4.50 and 6.75 g/day, and sevelamer carbonate 4.80 g/day (mean change -1.6 (-2.2, -1.0), -1.8 (-2.4, -1.2), and -1.4 (-2.2, -0.5) mg/dL, respectively). In both Parts, serum phosphorus reductions occurred within 1 week of VS-505 initiation, returning to baseline within 2 weeks of VS-505 discontinuation. CONCLUSION: VS-505, a novel phosphate binder, was well tolerated with a manageable safety profile, and effectively and dose-dependently reduced serum phosphorus in CKD patients with hyperphosphatemia receiving MHD. Clinical Trial registration number: NCT04551300.
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Cobalt (Co)-based materials have been widely investigated as hopeful noble-metal-free alternatives for the oxygen evolution reaction (OER) in alkaline electrolytes, which is crucial for generating hydrogen by water electrolysis. Herein, cobalt-based telluride particles with good electronic conductivity as anodic electrocatalysts were prepared under vacuum by the solid-state strategy, which display remarkable activities toward the OER. Nickel (Ni) and iron (Fe) codoped cobalt telluride (NiFe-CoTe) exhibits an overpotential of 321 mV to achieve a current density of 10 mA cm-2 and a Tafel slope of 51.8 mV dec-1, outperforming the performances of CoTe, CoTe2, and IrO2. According to the DFT calculation, the adsorbed hydroxyl-assisted adsorbate evolution mechanism was proposed for the OER process of NiFe-CoTe, which reveals the synergetic effect toward OER induced by codoping of the Ni and Fe atoms. This work proposes a rational strategy to prepare cobalt-based tellurides as efficient OER catalysts in alkaline electrolytes, providing a new strategy to prepare and regulate metal-based tellurides for catalysis and beyond.
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Sustainably feeding a growing population is a grand challenge, and one that is particularly difficult in regions that are dominated by smallholder farming. Despite local successes, mobilizing vast smallholder communities with science- and evidence-based management practices to simultaneously address production and pollution problems has been infeasible. Here we report the outcome of concerted efforts in engaging millions of Chinese smallholder farmers to adopt enhanced management practices for greater yield and environmental performance. First, we conducted field trials across China's major agroecological zones to develop locally applicable recommendations using a comprehensive decision-support program. Engaging farmers to adopt those recommendations involved the collaboration of a core network of 1,152 researchers with numerous extension agents and agribusiness personnel. From 2005 to 2015, about 20.9 million farmers in 452 counties adopted enhanced management practices in fields with a total of 37.7 million cumulative hectares over the years. Average yields (maize, rice and wheat) increased by 10.8-11.5%, generating a net grain output of 33 million tonnes (Mt). At the same time, application of nitrogen decreased by 14.7-18.1%, saving 1.2 Mt of nitrogen fertilizers. The increased grain output and decreased nitrogen fertilizer use were equivalent to US$12.2 billion. Estimated reactive nitrogen losses averaged 4.5-4.7 kg nitrogen per Megagram (Mg) with the intervention compared to 6.0-6.4 kg nitrogen per Mg without. Greenhouse gas emissions were 328 kg, 812 kg and 434 kg CO2 equivalent per Mg of maize, rice and wheat produced, respectively, compared to 422 kg, 941 kg and 549 kg CO2 equivalent per Mg without the intervention. On the basis of a large-scale survey (8.6 million farmer participants) and scenario analyses, we further demonstrate the potential impacts of implementing the enhanced management practices on China's food security and sustainability outlook.
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Agricultura/métodos , Conservação dos Recursos Naturais , Produtos Agrícolas/crescimento & desenvolvimento , Eficiência Organizacional , Fazendeiros , China , Técnicas de Apoio para a Decisão , Grão Comestível/crescimento & desenvolvimento , Política Ambiental , Fertilizantes/estatística & dados numéricos , Abastecimento de Alimentos/métodos , Efeito Estufa , Nitrogênio/metabolismo , Oryza/crescimento & desenvolvimento , Triticum/crescimento & desenvolvimento , Zea mays/crescimento & desenvolvimentoRESUMO
BACKGROUND: Peroral endoscopic myotomy (POEM) has emerged as a widely accepted treatment for achalasia, with limited studies for over 2 years. Additionally, traditional measurements of achalasia after POEM have deficiencies. The study aimed to analyze the long-term outcomes of POEM under different criteria. METHODS: Patients with achalasia who received POEM between November 2012 and March 2021 were recruited. Patients and characteristics were shown, and risk factors related to two novel definitions of recurrence, symptomatic reflux, and reflux esophagitis were analyzed. RESULTS: Three hundred and twenty-one patients were included. At a median follow-up of 52 months, twenty-three failures happened (7.17%) under the modified criterion, and forty-seven failures occurred (14.64%) under the normal standard. Hospitalization (P = 0.027) and esophageal myotomy length (P = 0.039) were significantly associated with long-term efficacy under the modified and normal criteria, respectively. Fifty-two patients (16.20%) reported reflux symptoms and endoscopy performed in 88 patients revealed reflux esophagitis in 22 cases (25.00%). There were no predictors in the analysis of symptomatic reflux and gender (P = 0.010), LESP (P = 0.013), IRP (P = 0.015), and the esophageal myotomy length (P = 0.032) were statistically related to reflux esophagitis. CONCLUSION: POEM is an extremely safe and effective treatment for achalasia with long-term follow-up. Shorter hospitalization and shorter esophageal myotomy length may decrease the incidence of recurrence under the modified and normal criteria, respectively. Long-term outcomes of POEM are unpredictable. No risk factors were related to symptomatic reflux, and male patients with low preoperative LESP and IRP needed relatively shorter esophageal myotomy to prevent reflux esophagitis.
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Acalasia Esofágica , Humanos , Acalasia Esofágica/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Resultado do Tratamento , Miotomia/métodos , Cirurgia Endoscópica por Orifício Natural/métodos , Recidiva , Idoso , Seguimentos , Esofagoscopia/métodos , Estudos Retrospectivos , Adulto Jovem , Adolescente , Esofagite Péptica/etiologia , Esofagite Péptica/prevenção & controle , Fatores de RiscoRESUMO
To investigate the efficacy and safety of continuous blood purification (CBP) in neonates with septic shock and acute kidney injury (AKI). This retrospective study was conducted at two tertiary care children's hospitals between January 2015 and May 2022. A total of 26 neonates with septic shock and AKI were included in this study, with a mortality rate of 50%. Fourteen neonates (53.8%) received continuous veno-venous hemodiafiltration, and 12 (46.2%) received continuous veno-venous hemofiltration. Compared with the indices before CBP, urine output increased 12 h after CBP initiation (P = 0.003) and serum creatinine decreased (P = 0.019). After 24 h of CBP, blood urea nitrogen had decreased (P = 0.006) and mean arterial pressure had increased (P = 0.007). At the end of CBP, the vasoactive-inotropic score and blood lactate were decreased (P = 0.035 and 0.038, respectively) and PH was increased (P = 0.015). Thrombocytopenia was the most common complication of CBP. Conclusion: CBP can efficiently maintain hemodynamic stability, improve renal function, and has good safety in neonates with septic shock and AKI. However, the mortality rate remains high, and whether CBP improves the prognosis of neonates with septic shock and AKI remains unclear. What is Known: ⢠Over 50% of children with septic shock have severe AKI, of which 21.6% required CBP. ⢠The clinical application of CBP in septic shock has attracted increasing attention. What is New: ⢠CBP can efficiently maintain hemodynamic stability, improve renal function, and has good safety in neonates with septic shock and AKI. ⢠The mortality rate in neonates with septic shock and AKI receiving CBP remains high.
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Injúria Renal Aguda , Choque Séptico , Criança , Recém-Nascido , Humanos , Choque Séptico/complicações , Choque Séptico/terapia , Estudos Retrospectivos , Prognóstico , Injúria Renal Aguda/terapia , Injúria Renal Aguda/etiologia , Nitrogênio da Ureia SanguíneaRESUMO
BACKGROUND: Atypical chronic myeloid leukemia (aCML) is a highly aggressive type of blood cancer that falls under the category of myelodysplastic/myeloproliferative neoplasms (MDS/MPN). In the fifth edition of the WHO classification of tumors, this category has been renamed MDS/MPN with neutrophilia. Although eosinophilia is commonly observed in blood cancers, it is rarely seen in aCML. CASE PRESENTATION: This study presents a case of aCML that was diagnosed six years after the patient developed eosinophilia. The patient had undergone tests to rule out other primary and secondary diseases, but the eosinophilia remained unexplained. Treatment with corticosteroids and hydroxyurea had proven ineffective. Six years later, the patient experienced an increase in white blood cells, primarily neutrophils. After ruling out other possible diagnoses, a combination of morphologic and molecular genetic findings led to the diagnosis of aCML. The patient responded well to treatment with azacitidine. CONCLUSIONS: This study summarizes the current state of aCML diagnosis and management and discusses the possible connection between eosinophilia and aCML.
Assuntos
Eosinofilia , Humanos , Eosinofilia/diagnóstico , Eosinofilia/complicações , Masculino , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/diagnóstico , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/tratamento farmacológico , Fatores de Tempo , IdosoRESUMO
BACKGROUND: Neonatal respiratory distress syndrome (NRDS) is a prevalent cause of respiratory failure and death among newborns, and prompt diagnosis is imperative. Historically, diagnosis of NRDS relied mostly on typical clinical manifestations, chest X-rays, and CT scans. However, recently, ultrasound has emerged as a valuable and preferred tool for aiding NRDS diagnosis. Nevertheless, evaluating lung ultrasound imagery necessitates rigorous training and may be subject to operator-dependent bias, limiting its widespread use. As a result, it is essential to investigate a new, reliable, and operator-independent diagnostic approach that does not require subjective factors or operator expertise. This article aims to explore the diagnostic potential of ultrasound-based radiomics in differentiating NRDS from other non-NRDS lung disease. METHODS: A total of 150 neonatal lung disease cases were consecutively collected from the department of neonatal intensive care unit of the Quanzhou Maternity and Children's Hospital, Fujian Province, from September 2021 to October 2022. Of these patients, 60 were diagnosed with NRDS, whereas 30 were diagnosed with neonatal pneumonia, meconium aspiration syndrome (MAS), and transient tachypnea (TTN). Two ultrasound images with characteristic manifestations of each lung disease were acquired and divided into training (n = 120) and validation cohorts (n = 30) based on the examination date using an 8:2 ratio. The imaging texture features were extracted using PyRadiomics and, after the screening, machine learning models such as random forest (RF), logistic regression (LR), K-nearest neighbors (KNN), support vector machine (SVM), and multilayer perceptron (MLP) were developed to construct an imaging-based diagnostic model. The diagnostic efficacy of each model was analyzed. Lastly, we randomly selected 282 lung ultrasound images and evaluated the diagnostic efficacy disparities between the optimal model and doctors across differing levels of expertise. RESULTS: Twenty-two imaging-based features with the highest weights were selected to construct a predictive model for neonatal respiratory distress syndrome. All models exhibited favorable diagnostic performances. Analysis of the Youden index demonstrated that the RF model had the highest score in both the training (0.99) and validation (0.90) cohorts. Additionally, the calibration curve indicated that the RF model had the best calibration (P = 0.98). When compared to the diagnostic performance of experienced and junior physicians, the RF model had an area under the curve (AUC) of 0.99; however, the values for experienced and junior physicians were 0.98 and 0.85, respectively. The difference in diagnostic efficacy between the RF model and experienced physicians was not statistically significant (P = 0.24), whereas that between the RF model and junior physicians was statistically significant (P < 0.0001). CONCLUSION: The RF model exhibited excellent diagnostic performance in the analysis of texture features based on ultrasound radiomics for diagnosing NRDS.