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With the emergence of digital transformation, China confronts the dual challenge of fostering sustainable economic and social development while fulfilling its "dual-carbon" commitments. Is the digital-real economy integration a blessing or a curse for inclusive green development? The study was conducted under this backdrop. This paper explores the impacts and mechanisms of digital-real economy integration on carbon emission efficiency, utilizing panel data from 274 Chinese cities over the period from 2011 to 2021. The results indicate that this profound integration significantly enhances urban carbon emission efficiency, although this relationship is partially mediated by industrial structure upgrading. Additionally, natural resources dependence may compromise efficiency gains, exhibiting varying effects across different contexts. The impact of digital-real economy integration on carbon efficiency (Cee) manifests as a non-linear U-shaped relationship that intensifies with increased integration. Heterogeneity analysis reveals that major, eastern, coastal, and resource-scarce cities experience the most profound benefits. These findings highlight the urgency of advancing digital carbon neutrality and offer strategies for emerging economies to transcend traditional constraints, thereby achieving green economic recovery and inclusive development.
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The entry of Cd into soil-rice systems is a growing concern as it can pose potential risks to public health. To derive regional soil Cd threshold, a total of 333 paired soil and rice samples was collected in Anhui Province, Eastern China. The results showed that the total soil Cd and soil Zn/Cd were the most significant variables contributing to Cd content in polished rice. The Chinese Soil Quality Standards might overestimate risk posed by Cd-contaminated soil for rice production in the mining area due to high Zn/Cd values of some mining-associated soils. Cd levels in polished rice can be predictable using stepwise multiple linear regression (MLR) model. However, the derived soil Cd threshold based on the MLR model would be unrealistically high. The classification and regression tree method (CART) performed well in simulating Cd levels in polished rice and can be used to derive soil Cd threshold instead of MLR to minimize the uncertainty.
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Cadmio , Monitoreo del Ambiente , Oryza , Contaminantes del Suelo , Suelo , Cadmio/análisis , Contaminantes del Suelo/análisis , China , Suelo/química , Monitoreo del Ambiente/métodos , Modelos Lineales , MineríaRESUMEN
Reconfiguration of in situ heterojunction composites without interfacial resistance by substitution of homologous anions for the formation of gradient work function differences inducing the formation of built-in electric field is an effective strategy to enhance the charge separation efficiency. Herein, Te2-/ZnIn2S4-VS (Te2-/ZIS-VS) in situ heterojunction was synthesized by substitution of Te2- ions for S2- in ultrathin ZIS containing S vacancies, which can significantly promote photogenerated charge separation, surface electron enrichment, and CO2 adsorption/activation. The presence of S vacancies and adjacent Te2-/S2- double anions, the double active sites constructed by defect engineering promote the desorption of *CO molecules while inhibiting the protonation toward *CHO, which was more favorable for selective CO2 photoreduction to CO. The experimental results showed that the CO yield of Te2-/ZIS-VS was significantly increased to 672.1 µmol g-1 h-1 compared with pristine ZIS (54.3 µmol g-1 h-1) and the CO selectivity was close to 83 %. Notably, the life cycle assessment (LCA) of Te2-/Znln2S4 nanosheets with S-vacancy was performed. The evaluation results showed that most of the 17 impact categories showed low overall impact values and were environmentally friendly. Based on the results of this LCA, suggestions were put forward to further optimize the product to reduce carbon emissions.
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ETHNOPHARMACOLOGICAL RELEVANCE: Hand, foot, and mouth disease (HFMD) is mainly caused by various of enteroviruses such as enterovirus 71 (EVA71), coxsackievirus A16 (CVA16), CVA6, and CVA10 in infants and children under 5 years old. During the past 5 years, CVA4 has become the dominant pathogen resulting in HFMD in China. However, there are no effective vaccines and antiviral drugs available. Houttuynia cordata Thunb (HC). is a Chinese herbal medicine eaten as vegetables for treating viral infection diseases, but whether HC has anti-CVA4 effect remains unclear. AIM OF THE STUDY: In this study, we want to investigate the antiviral activity of HC against CVA4 in vitro and in vivo and elucidate the potential mechanism of HC against CVA4. MATERIALS AND METHODS: MTT assay were used to evaluate the cytotoxicity of HC. Virus titers assay, CPE assay, violet staining and immunofluorescence were used to investigate the antiviral effect of HC against CVA4. A 13-day-old suckling mice model was established to evaluate the therapeutic efficacy of HC against CVA4 infection. Western blot, qRT-PCR and time-of-drug addition assay were performed to elucidate the potential mechanism of HC against CVA4 infection. RESULTS: MTT assay indicated the cytotoxicity concentration of HC on Vero cells and RD cells were more than 1mg/ml, suggesting that the low cytotoxicity of HC. In vitro antiviral assay revealed that HC could dose-dependently prevent the CPE, suppress the release of newborn virus, and inhibit the replication of CVA4 by decreasing viral RNA transcription and protein expression with IC50 of 88.96 µg/mL. A time-of-addition assay showed that HC mainly exerted anti-CVA4 effect by inhibiting virus replication at the post-entry stage. In vivo results further demonstrated that HC could effectively prevent the lethal infection of CVA4 by promoting survival, improving clinical symptoms, prolonging the survival time, inhibiting excessive inflammatory responses, and reducing pathological injury in vivo. Mechanistic studies revealed inhibition of p38 MAPK and JNK pathway over-activation may be the primary mechanism of HC against CVA4 infection. CONCLUSION: In summary, our results for the first time demonstrated that HC not only effectively inhibited CVA4 replication, but also partially protected the lethal infection of CVA4 in vivo. Furthermore, pharmacological mechanism studies revealed that the primary mechanism of HC against CVA4 infection may be associated with its effect of inhibiting over-activation of p38 MAPK and JNK signaling pathways caused by enteroviruses. Our finding indicated that HC might be a potential innovative medicine for treating HFMD.
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Since the emergence of the coronavirus disease 2019 (COVID-19). Several autoimmune and subacute thyroiditis (SAT) cases are on the rise all over the world. COVID-19 vaccine-associated SAT cases have also been reported. In this article, we present our data on 5 vaccine-associated SAT cases. We evaluated the type of vaccine received, the time between vaccination and the onset of SAT symptoms, laboratory findings, treatments administered, and response to treatment. The age of patients ranged from 31 to 43 years old. Three (60 %) patients had been diagnosed as SAT after the first dose, and tow (40 %) after the second dose. Patients' symptoms appeared approximately 25.2 days (2-44) after vaccination. Subacute thyroiditis occurring after COVID-19 vaccination is rare, we hope practitioners should be early aware of post-vaccine SAT, that can improve clinical evolution and outcome.
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OBJECTIVES: To observe the effect of electroacupuncture on miR-142-5p and ADAMTS1/PI3K/AKT pathway in rats with ischemic stroke, so as to explore the regulatory mechanism of electroacupuncture on angiogenesis after ischemic stroke. METHODS: This study was divided into two parts. The first part of the experimentï¼SD rats were randomly divided into sham operation group, model group and electroacupuncture group. There were 20 rats in each group. The middle cerebral artery occlusion (MCAO) rat model was prepared using a modified Longa's method. In the electroacupuncture group, "Shuigou" (GV26) was selected for electroacupuncture intervention (4 Hz/20 Hz) for 30 min each time. The rats in the electroacupuncture group were given electroacupuncture immediately after successful modeling, once a day for 4 times. Hunter score and TTC staining were used to observe the neurological deficits and infarct volumes respectivelyï¼HE staining was used to observe the cortical pathological changesï¼immunohistochemistry was used to determine the changes of cerebral microvascular density. Real-time quantitative PCR and Western blot were used to observe the miR-142-5p expression, mRNA and protein expression levels of ADAMTS1, VEGF, PI3K, AKT, eNOS in ischemic cortex. The second part of the experimentï¼The rats were randomly divided into electroacupuncture+control group and electroacupuncture+miR-142-5p Antagomir group with 8 rats in each group. MCAO model was established after injection. Electroacupuncture+control group was given 0.9% sodium chloride solution injected into the right ventricle.The rats in the electroacupuncture+miR-142-5p Antagomir group were injected with miR-142-5p inhibitor into the right ventricle 30 min before modeling. Rats in electroacupuncture+control group and electroacupuncture+miR-142-5p Antagomir group were all given the same electroacupuncture treatment. Real-time fluorescence quantitative PCR was used to observe the effect of miR-142-5p Antagomir on the expression of miR-142-5p and ADAMTS1 mRNA. The effect of miR-142-5p Antagomir on ADAMTS1 protein was observed by Western blot. RESULTS: In the first part of the experiment, compared with the sham operation group, the Hunter score in the model group was significantly increased (P<0.01)ï¼the volume of cerebral infarction in the model group was significantly increased (P<0.01)ï¼the degree of brain edema and neuronal necrosis and the density of cerebral microvessels was increasedï¼the cerebral microvascular density was significantly increased (P<0.01)ï¼the expression levels of miR-142-5p and the mRNA expression levels of VEGF, AKT and eNOS were significantly decreased (P<0.01, P<0.05), and the protein expression levels of VEGF, p-AKT and eNOS were significantly down-regulated (P<0.01), while the mRNA expression levels of ADAMTS1 and PI3K, and the protein expression levels of ADAMTS1 and p-PI3K were all up-regulated (P<0.01, P<0.05) in the model group. Compared with the model group, after intervention, the Hunter score in the electroacupuncture group was decreased (P<0.01), the volume of cerebral infarction was significantly decreased (P<0.01)ï¼the degree of brain edema and neuronal necrosis were alleviatedï¼the cerebral microvascular density was significantly increased (P<0.01)ï¼the expression of miR-142-5p and the mRNA expression of VEGF, PI3K, AKT and eNOS were increased (P<0.01), the protein expressions of VEGF, p-PI3K, p-AKT and eNOS were increased (P<0.01, P<0.05), while the mRNA and protein expression of ADAMTS1 were decreased (P<0.05, P<0.01). After injection of miR-142-5p inhibitor, compared with electroacupuncture+control group, the expression of miR-142-5p in electroacupuncture+miR-142-5p Antagomir group was decreased(P<0.05), while the mRNA and protein expression of ADAMTS1 were increased (P<0.01, P<0.05). CONCLUSIONS: Electroacupuncture at GV26 can improve the neurological damage of ischemic stroke rats, reduce the volume of cerebral infarction and promote angiogenesis. The mechanism may be associated with the function of electroacupuncture in promoting the expression of miR-142-5p, so as to inhibit the expression of its target gene ADAMTS1, mediate the up-regulation of VEGF expression, activate PI3K/AKT pathway, promote the release of eNOS, and participate in promoting angiogenesis in ischemic stroke rats.
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Proteína ADAMTS1 , Electroacupuntura , MicroARNs , Proteínas Proto-Oncogénicas c-akt , Ratas Sprague-Dawley , Accidente Cerebrovascular , Animales , Ratas , MicroARNs/genética , MicroARNs/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Masculino , Proteína ADAMTS1/genética , Proteína ADAMTS1/metabolismo , Humanos , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/metabolismo , Accidente Cerebrovascular/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Isquemia Encefálica/terapia , Isquemia Encefálica/metabolismo , Isquemia Encefálica/genética , Transducción de Señal , Neovascularización Fisiológica/genética , AngiogénesisRESUMEN
Water adsorption energy, Eads, is a key physical quantity in sustainable chemical technologies such as (photo)electrocatalytic water splitting, water desalination, and water harvesting. In many of these applications, the electrode surface is operated outside the point (potential) of zero charge, which attracts counter-ions to form the electric double layer and controls the surface properties. Here, by applying density functional theory-based finite-field molecular dynamics simulations, we have studied the effect of water adsorption energy Eads on surface acidity and the Helmholtz capacitance of BiVO4 as an example of metal oxide electrodes with weakly chemisorbed water. This allows us to establish the effect of Eads on the coordination number, the H-bond network, and the orientation of chemisorbed water by comparing an oxide series composed of BiVO4, TiO2, and SnO2. In particular, it is found that a positive correlation exists between the degree of asymmetry ΔCH in the Helmholtz capacitance and the strength of Eads. This correlation is verified and extended further to graphene-like systems with physisorbed water, where the electric double layers (EDLs) are controlled by electronic charge rather than proton charge as in the oxide series. Therefore, this work reveals a general relationship between water adsorption energy Eads and EDLs, which is relevant to both electrochemical reactivity and the electrowetting of aqueous interfaces.
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Agricultural droughts are a threat to local economies, as they disrupt crops. The monitoring of agricultural droughts is of practical significance for mitigating loss. Even though satellite data have been extensively used in agricultural studies, realizing wide-range, high-resolution, and high-precision agricultural drought monitoring is still difficult. This study combined the high spatial resolution of unmanned aerial vehicle (UAV) remote sensing with the wide-range monitoring capability of Landsat-8 and employed the local average method for upscaling to match the remote sensing images of the UAVs with satellite images. Based on the measured ground data, this study employed two machine learning algorithms, namely, random forest (RF) and eXtreme Gradient Boosting (XGBoost1.5.1), to establish the inversion models for the relative soil moisture. The results showed that the XGBoost model achieved a higher accuracy for different soil depths. For a soil depth of 0-20 cm, the XGBoost model achieved the optimal result (R2 = 0.6863; root mean square error (RMSE) = 3.882%). Compared with the corresponding model for soil depth before the upscaling correction, the UAV correction can significantly improve the inversion accuracy of the relative soil moisture according to satellite remote sensing. To conclude, a map of the agricultural drought grade of winter wheat in the Huaibei Plain in China was drawn up.
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BACKGROUND: Gene methylation and the immune-related tumor microenvironment (TME) are highly correlated in tumor progression and therapeutic efficacy. Although both of them can be used to predict the clinical outcomes of colorectal cancer (CRC) patients, their predictive value is still unsatisfactory. Whether a combination risk model comprising these two prediction parameters performs better predictive effectiveness than independent factor is still unclear. Methylated Septin9 (mSEPT9) is an early diagnosis biomarker of CRC, in this study, we aimed to investigate mSEPT9-related biomarkers of immunosuppressive TME and identify the value of the combination risk model in predicting the clinical outcomes of CRC. METHODS: Immunofluorescence staining was performed to clarify the correlation between intratumoral IL-10+ Treg infiltration and mSEPT9 in peripheral blood. Survival time, response to 5-fluorouracil (5-FU)-based chemotherapy and PD-1 blockade, and the probability of recurrence or metastasis were analyzed in study (197 CRC samples) and validation (195 CRC samples) sets to evaluate the efficacy of combination risk model. Potential mechanisms were explored by mRNA sequencing. RESULTS: Hypermethylated SEPT9 in the peripheral blood of patients with CRC (stage I-III, and stage IV with resectable M1) before radical resection was positively correlated with high intratumoral IL-10+ Treg infiltration. The high-risk model revealed poor overall survival and progression-free survival, inferior therapeutic response to 5-FU-based chemotherapy and PD-1 blockade, and high probability of recurrence or metastasis. The underlying mechanisms may be associated with the increase in mSEPT9 and mediation of IL-10 via methionine metabolic reprogramming-induced infiltration of IL-10+ Tregs in the TME, which promotes tumor progression and resistance to 5-FU-based chemotherapy and PD-1 blockade. CONCLUSIONS: The combination risk model of peripheral mSETP9 and intratumoral IL-10+ Treg infiltration in CRC can effectively predict prognosis, responsiveness to 5-FU-based chemotherapy and PD-1 blockade, and the probability of recurrence or metastasis. Therefore, this model can be used for precision treatment of CRC.
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Neoplasias Colorrectales , Metilación de ADN , Interleucina-10 , Nomogramas , Septinas , Linfocitos T Reguladores , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/inmunología , Septinas/genética , Septinas/metabolismo , Interleucina-10/genética , Interleucina-10/metabolismo , Linfocitos T Reguladores/inmunología , Masculino , Femenino , Persona de Mediana Edad , Resultado del Tratamiento , Microambiente Tumoral/inmunología , Pronóstico , Anciano , Fluorouracilo/uso terapéuticoRESUMEN
The L-isoleucine-4-dioxygenase converts L-isoleucine (Ile) into(2S,3R,4S)-4-(OH)-isoleucine (4-HIL), a naturally occurring hydroxyl amino acid, which is a promising compound for drug and functional food development. Here, a novel L-isoleucine-4-dioxygenase (RaIDO) from Rahnella aquatilis was cloned, expressed and characterized, as one of only a few reported L-isoleucine-4-dioxygenases. RaIDO showed high catalytic efficiency with Ile as the substrate, as well as good stability. HPLC-MS and NMR confirmed that RaIDO converts Ile into (2S,3R,4S)-4-(OH)-isoleucine. Further, structural analysis of RaIDO revealed key active site residues, including H159, D161 and H212. The RaIDO enzyme showed an optimal reaction temperature range of 30°C-45 °C, with the highest catalytic activity observed at 40 °C. Additionally, the enzyme exhibited an optimal pH of 8.0. Thus, the novel L-isoleucine-4-dioxygenase (RaIDO) has high catalytic efficiency and good stability, making it a strong candidate for industrial applications.
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Photodynamic therapy (PDT) has significant advantages in the treatment of malignant lung tumors. The research on the mechanism of PDT mediated by hematoporphyrin derivatives (HPD) and its cytotoxic effects on lung cancer cells has primarily focused on lung adenocarcinoma cells. However, the impact of HPD-PDT on lung squamous cell carcinoma has not been thoroughly studied. This study aimed to investigate the effects of 630 nm laser on apoptosis, metastasis, invasion, and epithelial-mesenchymal transition (EMT) in human lung squamous cell carcinoma H520 cells mediated by HPD. H520 cells were divided into four groups: control group, photosensitizer group, irradiation group, and HPD-PDT group. Cell proliferation was assessed using CCK8 assay; cell apoptosis was detected by Hoechst 33258 staining and flow cytometry; cell migration and invasion abilities were evaluated using wound-healing and invasion assays; and protein and mRNA expressions were analyzed by Western blot and reverse transcription-polymerase chain reaction (RT-PCR) respectively. Results showed that HPD-PDT significantly inhibited cell proliferation, promoted apoptosis (P < 0.05), suppressed cell migration and invasion (P < 0.05), decreased Bcl-2 mRNA expression, and increased Bax and Caspase-9 mRNA expression(P < 0.05). Western blotting analysis indicated increased expression of Bax, Caspase-9, and E-cadherin, and decreased expression of Bcl-2, N-cadherin, and Vimentin (P < 0.05). In conclusion, 630 nm laser mediated by HPD promoted cell apoptosis via upregulation of Bax and caspase-9, and downregulation of Bcl-2, and inhibited cell migration and invasion by regulating EMT in H520 cells.
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Apoptosis , Carcinoma de Células Escamosas , Movimiento Celular , Proliferación Celular , Transición Epitelial-Mesenquimal , Neoplasias Pulmonares , Invasividad Neoplásica , Fotoquimioterapia , Humanos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de la radiación , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/tratamiento farmacológico , Línea Celular Tumoral , Fotoquimioterapia/métodos , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/tratamiento farmacológico , Movimiento Celular/efectos de los fármacos , Movimiento Celular/efectos de la radiación , Proliferación Celular/efectos de los fármacos , Proliferación Celular/efectos de la radiación , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Derivado de la Hematoporfirina/farmacología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/genética , Cadherinas/metabolismo , Vimentina/metabolismo , Caspasa 9/metabolismo , Caspasa 9/genéticaRESUMEN
Diabetic gastroparesis, a common complication of type 2 diabetes (T2DM), presents a significant treatment challenge. FoxiangSan is emerging as a potential therapy. FoxiangSan is a traditional Chinese medicine formula with the potential for treating diabetic gastroparesis by modulating gut microbiota and cAMP/PKA signaling pathways. This study explores the mechanisms behind FoxiangSan's effects on T2DM-induced gastroparesis, focusing on its impact on gut microbiota and the cAMP/PKA pathway. A rat model of type 2 diabetic gastroparesis was established through a high-fat diet and streptozotocin (STZ) injection, and the effects of FoxiangSan were assessed. Additionally, protein expression related to the cAMP/PKA pathway was examined, and FoxiangSan's influence on gut microbiota was studied using 16S rRNA sequencing. FoxiangSan significantly alleviated hyperglycemia, improved gastric pathology in rats with gastroparesis, enhanced the expression of 5-HT4, cAMP, PKA, and pPKA in the gastric antrum, and rebalanced gut microbiota. FoxiangSan demonstrates the therapeutic potential for T2DM-associated gastroparesis by modulating the cAMP/PKA pathway and gut microbiota.
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Developing an effective and user-friendly hemostatic agent is highly desired in the treatment of hemorrhage. Inspired by the natural nanostructure and abundant hydroxyl groups of cellulose and clay minerals, we designed an aerogel (HNTs/TOCNs) composed of halloysite nanotubes (HNTs) and TEMPO-oxidized cellulose nanofibers (TOCNs) with a hierarchical porous structure for the treatment of bleeding, using a simple and environmentally friendly self-assembly method. TOCNs formed a three-dimensional porous scaffold with excellent water-holding capacity. The incorporation of HNTs enhanced the hemostatic efficiency and mechanical properties of the 3D framework. The large interlayer spaces and wide channels within the HNTs/TOCNs aerogel provided rapid passage for blood, facilitating blood concentration and offering ample room for interactions between the HNTs/TOCNs aerogel and platelets, erythrocytes, and coagulation factors, thereby promoting hemostasis. Benefiting from the natural hemostatic properties and well-designed structure, the HNTs/TOCNs aerogel displayed excellent hemostatic performance both in vitro and in vivo. Notably, the hemostatic time of HNTs/TOCNs-2 was only 74 ± 8 s, which is approximately 50 % shorter than the blank control (151 ± 20 s) in liver femoral artery injury model. This design of an HNTs/TOCNs aerogel presents a unique opportunity to enhance hemostatic efficacy by synergizing the advantages of natural materials.
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Celulosa , Arcilla , Hemostasis , Nanofibras , Nanofibras/química , Porosidad , Animales , Hemostasis/efectos de los fármacos , Arcilla/química , Celulosa/química , Geles/química , Hemostáticos/química , Hemostáticos/farmacología , Ratas , Hemorragia/tratamiento farmacológico , Masculino , Nanotubos/química , Óxidos N-Cíclicos/química , RatonesRESUMEN
The adsorption of nitrate is the key to enhancing the electrocatalytic nitrate reduction reaction (NitRR). Herein, a typical hydrolysis-coupled redox (HCR) reaction has been designed to prepare unique 3D Cu/Fe2O3 core-shell nanorod array cathodes with controllable oxygen vacancy concentrations for NitRR. The optimal Cu/Fe2O3-13 achieves a high nitrate conversion of 99.10% and ammonia selectivity of 98.30%. The outstanding electrochemical performance is attributed to the enhancement mechanism of OVs and a unique nanorod array structure with a high density of surface-exposed OVs and high-throughput transport pathways for ion-aspects.
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BACKGROUND: In 2016, China has implemented the World Health Organization's "treat all" policy. We aimed to assess the impact of significant improvements in the 95-95-95 targets on population-level human immunodeficiency virus (HIV) transmission dynamics and incidence. METHODS: We focused on 3 steps of the HIV care continuum: diagnosed, on antiretroviral therapy, and achieving viral suppression. The molecular transmission clusters were inferred using HIV-TRACE. New HIV infections were estimated using the incidence method in the European Centre for Disease Prevention and Control HIV Modelling Tool. RESULTS: Between 2004 and 2023, the national HIV epidemiology database recorded 2.99 billion person-times of HIV tests and identified 1 976 878 new diagnoses. We noted a roughly "inverted-V" curve in the clustering frequency, with the peak recorded in 2014 (67.1% [95% confidence interval, 63.7%-70.5%]), concurrent with a significant improvement in the 95-95-95 targets from 10-13-<71 in 2005 to 84-93-97 in 2022. Furthermore, we observed a parabolic curve for a new infection with the vertex occurring in 2010. CONCLUSIONS: In general, it was suggested that the improvements in the 95-95-95 targets were accompanied by a reduction in both the population-level HIV transmission rate and incidence. Thus, China should allocate more effort to the first "95" target to achieve a balanced 95-95-95 target.
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BACKGROUND: National treatment guidelines of China evolving necessitates population-level surveillance of transmitted drug resistance (TDR) to inform or update HIV treatment strategies. METHODS: We analyzed the demographic, clinical, and virologic data obtained from people with HIV (PWH) residing in 31 provinces of China who were newly diagnosed between 2018 and 2023. Evidence of TDR was defined by the World Health Organization list for surveillance of drug resistance mutations. RESULTS: Among the 22 124 PWH with protease and reverse transcriptase sequences, 965 (4.36%; 95% CI, 4.1-4.63) had at least 1 TDR mutation. The most frequent TDR mutations were nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations (2.39%; 95% CI, 2.19%-2.59%), followed by nucleoside reverse transcriptase inhibitor mutations(1.35%; 95% CI, 1.2%-1.5%) and protease inhibitor mutations (1.12%; 95% CI, .98%-1.26%). The overall protease and reverse transcriptase TDR increased significantly from 4.05% (95% CI, 3.61%-4.52%) in 2018 to 5.39% (95% CI, 4.33%-6.57%) in 2023. A low level of integrase strand transfer inhibitor TDR was detected in 9 (0.21%; 95% CI, .1%-.38%) of 4205 PWH. CONCLUSIONS: Presently, the continued use of NNRTI-based first-line antiretroviral therapy regimen for HIV treatment has been justified.
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In this paper, we study the robust estimation and empirical likelihood for the regression parameter in generalized linear models with right censored data. A robust estimating equation is proposed to estimate the regression parameter, and the resulting estimator has consistent and asymptotic normality. A bias-corrected empirical log-likelihood ratio statistic of the regression parameter is constructed, and it is shown that the statistic converges weakly to a standard χ 2 distribution. The result can be directly used to construct the confidence region of regression parameter. We use the bias correction method to directly calibrate the empirical log-likelihood ratio, which does not need to be multiplied by an adjustment factor. We also propose a method for selecting the tuning parameters in the loss function. Simulation studies show that the estimator of the regression parameter is robust and the bias-corrected empirical likelihood is better than the normal approximation method. An example of a real dataset from Alzheimer's disease studies shows that the proposed method can be applied in practical problems.
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Limb-girdle muscular dystrophy type 2A (LGMD R1 Calpain 3-Related, LGMD2A/R1), an autosomal recessive disorder, is characterized by progressive muscle weakness with a prominent presentation in the proximal limb girdle muscles. LGMD2A/R1, which is caused by variants in calcium-activated neutral proteinase 3 (CAPN3), is the most common. The present study aimed at identifying the clinically significant variants in a Chinese family with LGMD2A/R1 and exploring the genotype-phenotype correlations. Clinical symptoms, laboratory findings, and physical examinations were obtained. Genomic DNA was extracted from the peripheral blood samples of this family. Whole-exome sequencing (WES) and Sanger sequencing were used to explore and validate the pathogenic genes. In this study, the proband and his sister, who had two identical mutations in the CAPN3 gene sequence, exhibited diverse clinical features, including disease onset and progression. The mutation c.2120 A>G (p. D707G) is pathogenic and has been reported in the Human Gene Mutation Database (HGMD) and the ClinVar database. c.1783-72 C>G may be a novel pathogenic mutation of LGMD2A/R1 based on the American College of Medical Genetics (ACMG) guidelines, which widens the gene variant pool in CAPN3 and improves diagnosis and genetic counseling.