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1.
Quant Imaging Med Surg ; 14(10): 7330-7340, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39429559

RESUMEN

Background: Early detection of nasopharyngeal carcinoma (NPC) patients who are not sensitive to neoadjuvant chemotherapy (NAC) can guard against overtreatment. This study aimed to evaluate the effectiveness of amide proton transfer (APT) imaging and diffusion-weighted imaging (DWI) in predicting the early response to NAC in patients with NPC. Methods: This prospective study enrolled fifty patients with biopsy-confirmed NPC from September 2021 to May 2023. Magnetic resonance imaging (MRI) including APT and DWI, was performed before NAC. After NAC, patients were divided into complete response (CR), partial response (PR), and stable disease (SD) and progressive disease (PD) groups based on the Response Evaluation Criteria in Solid Tumours Version 1.1. The Kruskal-Wallis H test was used for statistical analysis. The differences in APT and apparent diffusion coefficient (ADC) values among the different efficacy groups were compared, the receiver operating characteristic (ROC) curve was drawn for statistically significant parameters, and the area under the curve (AUC) was calculated. Results: Fifty patients (mean age: 47±14 years; 42 males and 8 females) were included in the final analysis (11 were in the CR group, 30 in the PR group, 9 in the SD group, and 0 in the PD group). The ADC values showed no significant differences among the different treatment response groups. The SD group showed significantly lower APTmax (P=0.025), APTskewness (P=0.025) and APT90% (P=0.001) values than the CR and PR groups. Setting APT90% =3.10% as the cut-off value, optimal diagnostic performance (AUC: 0.831; sensitivity: 0.778; specificity: 0.878) was obtained in predicting the SD group. Conclusions: APT imaging can predict the early tumour response to NAC in patients with NPC. APT imaging may be superior to DWI in predicting tumour response.

2.
J Am Acad Dermatol ; 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39182680

RESUMEN

BACKGROUND: Regulatory T cells (Tregs) are reduced in the peripheral blood and skin lesions of patients with bullous pemphigoid (BP). Low-dose interleukin 2 (IL-2) therapy can stimulate Tregs specifically, suggesting potential for the treatment of BP. OBJECTIVE: To evaluate the response to low-dose IL-2 therapy in the treatment of moderate-to-severe BP. METHODS: Forty-three patients with moderate-to-severe BP were included. The therapy included systemic corticosteroids with an initial dose of 0.5 mg/kg/d for moderate and 1.0 mg/kg/d for severe disease, respectively, combined with allowed immunosuppressants for the control group, whereas in addition to the same corticosteroid therapy, IL-2 (half million IU) was administered subcutaneously every other day for the treatment group for 8 weeks. The primary outcome was the number of days required to achieve disease control. Secondary outcomes included other clinical responses. RESULTS: The number of days required to achieve disease control with the treatment group was (7.60 ± 3.00), which was shorter than in the control group (10.43 ± 3.06) (P = .008). The total amount of systemic corticosteroids was less, and no serious infections were detected in the treatment group. LIMITATIONS: Single center, open-label study with short duration and small size. CONCLUSION: Our trial supports the potential of low-dose IL-2 therapy for patients with moderate-to-severe BP, which showed earlier treatment responses.

3.
Bioresour Technol ; 411: 131335, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39181511

RESUMEN

The amounts of gases emitted from composting are key to evaluating global warming potential (GWP). However, few methods can accurately predict the quantities of relevant gas emissions. In this study, three developed machine-learning models were used to predict NH3 emissions and GWP. The extreme gradient boosting model provided the best predictions (R2 > 90 %) compared to random forest, making it a suitable method for calculating NH3 emissions and GWP. The k-nearest neighbor classification model was utilized to determined compost maturity achieving 92 % accuracy. Shapley Additive ExPlanation analysis was applied to identify key factors influencing gas emissions and maturity. Aeration rate, carbon-to-nitrogen ratio and moisture content showed high importance in decreasing order for predicting NH3 emissions, while NO3- was the most significant factor for predicting GWP. Practical applications of predictive models suggested that prediction of GWP was 792614 Mg CO2e year-1 close to annual calculation of 789000 Mg CO2e year-1 in California.


Asunto(s)
Amoníaco , Compostaje , Calentamiento Global , Aprendizaje Automático , Amoníaco/análisis , Compostaje/métodos , Nitrógeno/análisis , Suelo/química
4.
Psychol Res Behav Manag ; 17: 2853-2863, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39099586

RESUMEN

Purpose: Hearing-impaired college students often rely on smartphones for information exchange and social interaction due to their hearing limitations, which may increase their risk of smartphone addiction. This study aims to explore the impact of executive dysfunction on anxiety levels in hearing-impaired college students, investigating smartphone addiction as a mediator and academic procrastination as a moderator. Methods: We conducted a questionnaire survey using the Executive Function Scale, the Anxiety Scale, the Smartphone Addiction Scale, and the Academic Procrastination Scale. The survey included 609 hearing-impaired college students from three universities in Jiangsu, Hunan, and Heilongjiang Provinces, China. Results: After controlling for age, executive dysfunction was found to significantly predict higher anxiety levels in hearing-impaired college students. Additionally, smartphone addiction partially mediated the relationship between executive dysfunction and anxiety. Academic procrastination further moderated the relationship between smartphone addiction and anxiety. Conclusion: This study enhances the understanding of the complex interactions between executive dysfunction, smartphone addiction, and academic procrastination in contributing to anxiety among hearing-impaired college students. The findings offer valuable insights for developing strategies to promote the mental health of this population.

6.
Quant Imaging Med Surg ; 14(7): 4763-4778, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-39022232

RESUMEN

Background: Early neurologic deterioration occurs in up to one-third of patients with acute ischemic stroke (IS), often leading to poor functional outcomes. At present, few studies have applied amide proton transfer (APT) imaging to the evaluation of early neurological deterioration (END). This study analyzed the value of computed tomography perfusion (CTP) combined with multimodal magnetic resonance imaging (MRI) in patients with acute IS with END. Methods: This retrospective study included patients with acute IS who were admitted to the neurology inpatient department in a tertiary hospital from October 2021 to June 2023. Patients with acute IS underwent CTP within 24 hours of stroke onset and MRI [arterial spin labeling (ASL), susceptibility-weighted imaging (SWI), and APT] within 7 days. END was defined as an elevation of ≥2 points on the National Institute of Health Stroke Scale (NIHSS) within 7 days of stroke onset. Univariable and multivariable analyses were used to compare clinical and imaging biomarkers in patients with acute IS with and without END. The performance of potential biomarkers in distinguishing between the two groups was evaluated using receiver operating characteristic (ROC) curve analysis. Results: Among the 70 patients with acute IS, 20 (29%) had END. After conducting univariable analysis, variables were selected for entry into a binary logistic regression analysis based on our univariable analysis results, previous research findings, clinical experience, and methodological standards. The results indicated that relative cerebral blood volume (CBV) on CTP, relative cerebral blood flow (CBF) on ASL, and relative signal intensity on amide proton transfer-weighted (APTw) imaging were independent risk factors for END. The areas under the ROC curves for these risk factors were 0.710 [95% confidence interval (CI): 0.559-0.861, P=0.006], 0.839 (95% CI: 0.744-0.933, P<0.001), and 0.804 (95% CI: 0.676-0.932, P<0.001), respectively. The combined area under the curve (AUC), sensitivity, and specificity of the four indices (0.941, 100%, and 78%, respectively) were higher than those of the four indices alone. Conclusions: CTP combined with multi-modal MRI better evaluated hemodynamics, tissue metabolism, and other relevant patient information, providing an objective basis for the clinical assessment of patients with acute IS with END and facilitating the development of accurate and personalized treatment plans.

7.
bioRxiv ; 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38798341

RESUMEN

TDP43 is an RNA/DNA binding protein increasingly recognized for its role in neurodegenerative conditions including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). As characterized by its aberrant nuclear export and cytoplasmic aggregation, TDP43 proteinopathy is a hallmark feature in over 95% of ALS/FTD cases, leading to the formation of detrimental cytosolic aggregates and a reduction in nuclear functionality within neurons. Building on our prior work linking TDP43 proteinopathy to the accumulation of DNA double-strand breaks (DSBs) in neurons, the present investigation uncovers a novel regulatory relationship between TDP43 and DNA mismatch repair (MMR) gene expressions. Here, we show that TDP43 depletion or overexpression directly affects the expression of key MMR genes. Alterations include MLH1, MSH2, MSH3, MSH6, and PMS2 levels across various primary cell lines, independent of their proliferative status. Our results specifically establish that TDP43 selectively influences the expression of MLH1 and MSH6 by influencing their alternative transcript splicing patterns and stability. We furthermore find aberrant MMR gene expression is linked to TDP43 proteinopathy in two distinct ALS mouse models and post-mortem brain and spinal cord tissues of ALS patients. Notably, MMR depletion resulted in the partial rescue of TDP43 proteinopathy-induced DNA damage and signaling. Moreover, bioinformatics analysis of the TCGA cancer database reveals significant associations between TDP43 expression, MMR gene expression, and mutational burden across multiple cancers. Collectively, our findings implicate TDP43 as a critical regulator of the MMR pathway and unveil its broad impact on the etiology of both neurodegenerative and neoplastic pathologies.

8.
J Cosmet Dermatol ; 23(7): 2386-2391, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38558364

RESUMEN

BACKGROUND: Micronized acellular dermal matrix (mADM) can induce tissue regeneration and repair, and filling. OBJECTIVES: The efficacy and safety of (mADM) were evaluated in the treatment of atrophic acne scar. METHODS: In this single-blinded, self-controlled, split-face study, 16 patients (48 scar sites) were divided into treatment group (24 scar sites) and control group (24 scar sites). One side of the affected area was treated with mADM combined with platelet rich plasma (PRP) injection as the treatment group; the other side of the affected area was treated with PRP injection as the control group. The efficacy was evaluated by the Acne scar assessment scale (ASAS) and Acne Scar Weight Rating Scale (ECCA) 3 months after treatment. RESULTS: After 3-month treatment in 16 patients, the atrophic acne scars in both groups were all improved. The ASAS score and ECCA weight score in the treatment group was significantly lower than that in the control group (2.50 ± 0.51 vs. 3.62 ± 0.77 and 14.17 ± 10.18 vs. 31.88 ± 13.25; p < 0.001). LIMITATIONS: Short-term 3-month treatment period. Small sample size limits generalizability of results. CONCLUSION: The curative effect of mADM combined with PRP is significantly better than that of PRP alone.


Asunto(s)
Dermis Acelular , Acné Vulgar , Atrofia , Cicatriz , Plasma Rico en Plaquetas , Humanos , Acné Vulgar/complicaciones , Acné Vulgar/terapia , Cicatriz/terapia , Cicatriz/etiología , Cicatriz/patología , Adulto , Femenino , Método Simple Ciego , Masculino , Atrofia/terapia , Atrofia/etiología , Adulto Joven , Resultado del Tratamiento , Cara , Terapia Combinada/métodos , Índice de Severidad de la Enfermedad , Técnicas Cosméticas/efectos adversos , Técnicas Cosméticas/instrumentación
10.
Proc Natl Acad Sci U S A ; 121(13): e2313652121, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38498709

RESUMEN

Huntington's disease (HD) is an inherited neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin (HTT) gene. The repeat-expanded HTT encodes a mutated HTT (mHTT), which is known to induce DNA double-strand breaks (DSBs), activation of the cGAS-STING pathway, and apoptosis in HD. However, the mechanism by which mHTT triggers these events is unknown. Here, we show that HTT interacts with both exonuclease 1 (Exo1) and MutLα (MLH1-PMS2), a negative regulator of Exo1. While the HTT-Exo1 interaction suppresses the Exo1-catalyzed DNA end resection during DSB repair, the HTT-MutLα interaction functions to stabilize MLH1. However, mHTT displays a significantly reduced interaction with Exo1 or MutLα, thereby losing the ability to regulate Exo1. Thus, cells expressing mHTT exhibit rapid MLH1 degradation and hyperactive DNA excision, which causes severe DNA damage and cytosolic DNA accumulation. This activates the cGAS-STING pathway to mediate apoptosis. Therefore, we have identified unique functions for both HTT and mHTT in modulating DNA repair and the cGAS-STING pathway-mediated apoptosis by interacting with MLH1. Our work elucidates the mechanism by which mHTT causes HD.


Asunto(s)
Enfermedad de Huntington , Humanos , Proteína Huntingtina/genética , Proteína Huntingtina/metabolismo , Proteínas Mutantes/genética , Enfermedad de Huntington/genética , Enfermedad de Huntington/metabolismo , Nucleotidiltransferasas/genética , ADN , Apoptosis/genética , Homólogo 1 de la Proteína MutL/genética
11.
Bioresour Technol ; 397: 130502, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38417463

RESUMEN

Branched-chain amino acids (BCAAs) such as L-valine, L-leucine, and L-isoleucine are widely used in food and feed. To comply with sustainable development goals, commercial production of BCAAs has been completely replaced with microbial fermentation. However, the efficient production of BCAAs by microorganisms remains a serious challenge due to their staggered metabolic networks and cell growth. To overcome these difficulties, systemic metabolic engineering has emerged as an effective and feasible strategy for the biosynthesis of BCAA. This review firstly summarizes the research advances in the microbial synthesis of BCAAs and representative engineering strategies. Second, systematic methods, such as high-throughput screening, adaptive laboratory evolution, and omics analysis, can be used to analyses the synthesis of BCAAs at the whole-cell level and further improve the titer of target chemicals. Finally, new tools and engineering strategies that may increase the production output and development direction of the microbial production of BCAAs are discussed.


Asunto(s)
Aminoácidos de Cadena Ramificada , Isoleucina , Aminoácidos de Cadena Ramificada/metabolismo , Leucina/metabolismo , Valina , Ingeniería Metabólica
12.
Nurs Open ; 11(1): e2077, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38268244

RESUMEN

AIM: To identify potential categories of clinical belonging among new nurses and explore the relationship between different categories and turnover intention. DESIGN: A cross sectional study. METHOD: A cross sectional study was conducted among 348 new nurses from tertiary hospitals in Hainan and Guangdong provinces. A general data questionnaire, clinical belonging scale and turnover intention scale were used for examination. Further, the potential categories were used to analyse the categories of clinical belonging, and latent class analysis was utilized to analyse the relationship between different categories of clinical belonging and turnover intention. RESULTS: The clinical sense of belonging of new nurses were divided into three groups namely C1, C2 and C3. The C1: poor clinical sense of belonging (8.7%), C2: moderate clinical sense of belonging (57.9%) and C3: rich clinical sense of belonging (33.4%). The risk of the turnover intention of new nurses with 'poor clinical sense of belonging' was 0.62 times that of new nurses with 'rich clinical sense of belonging' (OR = 0.62, p < 0.01), which was 0.24 times that of 'moderate clinical sense of belonging' (OR = 0.24, p < 0.01), the risk of the turnover intention of new nurses with 'moderate clinical sense of belonging' was 0.13 times that of new nurses with 'rich clinical sense of belonging'(OR = 0. 13, p < 0.01). CONCLUSIONS: The results of our study revealed that in order to enhance the new nurses' sense of belonging, support was most crucial when they were first encountering difficulties. To reduce turnover intention, more structured learning opportunities are also required to maximize learning for newly graduated nurses with various nursing degrees. PATIENT OR PUBLIC CONTRIBUTION: There are no patient or public contributions in this study.


Asunto(s)
Intención , Enfermeras y Enfermeros , Humanos , Análisis de Clases Latentes , Estudios Transversales , Aprendizaje
13.
Skin Res Technol ; 30(1): e13571, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38196164

RESUMEN

BACKGROUND: Nuclear pleomorphism and tumor microenvironment (TME) play a critical role in cancer development and progression. Identifying most predictive nuclei and TME features of basal cell carcinoma (BCC) may provide insights into which characteristics pathologists can use to distinguish and stratify this entity. OBJECTIVES: To develop an automated workflow based on nuclei and TME features from basaloid cell tumor regions to differentiate BCC from trichoepithelioma (TE) and stratify BCC into high-risk (HR) and low-risk (LR) subtypes, and to identify the nuclear and TME characteristics profile of different basaloid cell tumors. METHODS: The deep learning systems were trained on 161 H&E -stained sections which contained 51 sections of HR-BCC, 50 sections of LR-BCC and 60 sections of TE from one institution (D1), and externally and independently validated on D2 (46 sections) and D3 (76 sections), from 2015 to 2022. 60%, 20% and 20% of D1 data were randomly splitted for training, validation and testing, respectively. The framework comprised four stages: tumor regions identification by multi-head self-attention (MSA) U-Net, nuclei segmentation by HoVer-Net, quantitative feature by handcrafted extraction, and differentiation and risk stratification classifier construction. Pixel accuracy, precision, recall, dice score, intersection over union (IoU) and area under the curve (AUC) were used to evaluate the performance of tumor segmentation model and classifiers. RESULTS: MSA-U-Net model detected tumor regions with 0.910 precision, 0.869 recall, 0.889 dice score and 0.800 IoU. The differentiation classifier achieved 0.977 ± 0.0159, 0.955 ± 0.0181, 0.885 ± 0.0237 AUC in D1, D2 and D3, respectively. The most discriminative features between BCC and TE contained Homogeneity, Elongation, T-T_meanEdgeLength, T-T_Nsubgraph, S-T_HarmonicCentrality, S-S_Degrees. The risk stratification model can well predict HR-BCC and LR-BCC with 0.920 ± 0.0579, 0.839 ± 0.0176, 0.825 ± 0.0153 AUC in D1, D2 and D3, respectively. The most discriminative features between HR-BCC and LR-BCC comprised IntensityMin, Solidity, T-T_minEdgeLength, T-T_Coreness, T-T_Degrees, T-T_Betweenness, S-T_Degrees. CONCLUSIONS: This framework hold potential for future use as a second opinion helping inform diagnosis of BCC, and identify nuclei and TME features related with malignancy and tumor risk stratification.


Asunto(s)
Carcinoma Basocelular , Aprendizaje Profundo , Neoplasias Cutáneas , Humanos , Microambiente Tumoral , Carcinoma Basocelular/diagnóstico por imagen , Neoplasias Cutáneas/diagnóstico por imagen , Medición de Riesgo
14.
Cell Discov ; 9(1): 107, 2023 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-37907457

RESUMEN

Transcription-coupled nucleotide excision repair (TC-NER) is an important genome maintenance system that preferentially removes DNA lesions on the transcribed strand of actively transcribed genes, including non-coding genes. TC-NER involves lesion recognition by the initiation complex consisting of RNA polymerase II (Pol II) and Cockayne syndrome group B (CSB), followed by NER-catalyzed lesion removal. However, the efficient lesion removal requires the initiation complex to yield the right of way to the excision machinery, and how this occurs in a timely manner is unknown. Here we show that heat shock protein DNAJA2 facilitates the HSC70 chaperone-mediated autophagy (CMA) to degrade CSB during TC-NER. DNAJA2 interacts with and enables HSC70 to recognize sumoylated CSB. This triggers the removal of both CSB and Pol II from the lesion site in a manner dependent on lysosome receptor LAMP2A. Defects in DNAJA2, HSC70 or LAMP2A abolish CSB degradation and block TC-NER. Our findings discover DNAJA2-mediated CMA as a critical regulator of TC-NER, implicating the DNAJA2-HSC70-CMA axis factors in genome maintenance.

15.
Mol Cell ; 83(20): 3582-3587, 2023 10 19.
Artículo en Inglés | MEDLINE | ID: mdl-37863025

RESUMEN

In recent years, increasing evidence has highlighted the profound connection between DNA damage repair and the activation of immune responses. We spoke with researchers about their mechanistic interplays and the implications for cancer and other diseases.


Asunto(s)
Daño del ADN , Reparación del ADN , Transducción de Señal , Inmunidad
16.
Arthritis Res Ther ; 25(1): 204, 2023 10 18.
Artículo en Inglés | MEDLINE | ID: mdl-37853451

RESUMEN

OBJECTIVES: Juvenile dermatomyositis (JDM) is a chronic autoimmune disease. Some patients remain in an active state even though they were administrated with a combination of corticosteroid and methotrexate. Existing research has suggested that interferon and Janus kinase played an important role in pathogenesis. Existing research has suggested the efficacy of JAK inhibitors (JAKi). Our retrospective study aimed to investigate the efficacy of tofacitinib in refractory JDM patients. METHODS: A total of eighty-eight patients in China who had been diagnosed with JDM and subjected to tofacitinib therapy for over 3 months were retrospectively analyzed. Skin and muscle manifestations were assessed using the Cutaneous Assessment Tool-binary method (CAT-BM), Childhood Myositis Assessment Scale (CMAS), and kinase. Pulmonary function was assessed using a high-resolution CT (computerized tomography) scan and pulmonary symptoms. All patients were subjected to regular follow-up, and core measures were assessed every 3 months after initiation. Furthermore, the data were analyzed using the Wilcoxon single test, Mann-Whitney U test, and chi-square test. RESULTS: Compared with the baseline data, skin and muscle manifestations were found significantly improved during the respective follow-up visit. At the most recent follow-up, nearly 50% of patients achieved a clinical complete response and six patients received tofacitinib monotherapy. Sixty percent of patients suffering from interstitial lung disease well recovered on high-resolution CT. Seventy-five percent of patients showed a reduction in the size or number of calcinosis, and 25% of patients showed completely resolved calcinosis. CONCLUSION: In this study, the result suggested that tofacitinib therapy exerted a certain effect on skin manifestations, muscle manifestations, interstitial lung disease (ILD), calcinosis, as well as downgrade of medication. In-depth research should be conducted to focus on the correlation between the pathogenesis of JDM and JAKi.


Asunto(s)
Calcinosis , Dermatomiositis , Inhibidores de las Cinasas Janus , Enfermedades Pulmonares Intersticiales , Humanos , Niño , Dermatomiositis/diagnóstico , Estudios Retrospectivos , Inhibidores de las Cinasas Janus/uso terapéutico , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico
17.
Biotechnol Biofuels Bioprod ; 16(1): 145, 2023 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-37775757

RESUMEN

BACKGROUND: L-Leucine is a high-value amino acid with promising applications in the medicine and feed industries. However, the complex metabolic network and intracellular redox imbalance in fermentative microbes limit their efficient biosynthesis of L-leucine. RESULTS: In this study, we applied rational metabolic engineering and a dynamic regulation strategy to construct a plasmid-free, non-auxotrophic Escherichia coli strain that overproduces L-leucine. First, the L-leucine biosynthesis pathway was strengthened through multi-step rational metabolic engineering. Then, a cooperative cofactor utilization strategy was designed to ensure redox balance for L-leucine production. Finally, to further improve the L-leucine yield, a toggle switch for dynamically controlling sucAB expression was applied to accurately regulate the tricarboxylic acid cycle and the carbon flux toward L-leucine biosynthesis. Strain LEU27 produced up to 55 g/L of L-leucine, with a yield of 0.23 g/g glucose. CONCLUSIONS: The combination of strategies can be applied to the development of microbial platforms that produce L-leucine and its derivatives.

18.
Heliyon ; 9(7): e17744, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37539200

RESUMEN

The intelligent revolution caused by new digital technologies has provided new impetus to reduce carbon emissions. However, the current research on new digital technologies and carbon emissions is still in its infancy and lacks empirical conclusions between them. Therefore, this paper studies the impact of new digital technologies on carbon emissions, identifies its mechanism, and analyzes the regional heterogeneity of its effects. This research treats the National Big Data Comprehensive Pilot Zones pilot in China as a quasi-natural experiment for the development of new digital technologies along with city-level data covering from 2011 to 2019 to conduct a staggered difference-in-difference (DID) model analysis. We find that new digital technologies significantly reduce carbon emissions. This conclusion is still valid after a series of robustness tests such as heterogeneity treatment effect analysis, ex-ante trend test, spillover effect test, and placebo test. Additionally, new digital technologies can reduce carbon emissions by promoting the transformation of industrial structure, improving the level of green technology innovation, and promoting industrial agglomeration. At the same time, the heterogeneity analysis shows that new digital technologies' carbon emission reduction effect is more evident in non-western regions, southern regions, and large cities. To expand the carbon emission reduction effect of new digital technologies, the government should promote the development and application of new digital technologies, and implement differentiated policies based on regional characteristics.

19.
Front Pediatr ; 11: 1194214, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37614903

RESUMEN

Objectives: The study aimed to describe the characteristics of gastrointestinal (GI) involvement in a cohort of hospitalized children with IgA vasculitis (IgAV) in China. Method: We reviewed the records of hospitalized IgAV patients from January 2014 to December 2020 at one tertiary medical center. The patients were divided into the severe GI group and the non-severe GI group according to the presence of massive GI bleeding and complications. The clinical manifestations, laboratory factors, and treatment were analyzed between the two groups. Results: A total of 1,179 patients were hospitalized due to IgAV. GI involvement was noted in 50% (589) of the patients, of whom 288 (48.9%) had severe GI involvement. GI complications were observed in 34 patients with IgAV with GI involvement. Rare onset age (<3 years or within 13-17 years), purpura above the waist, vomiting, high neutrophil-to-lymphocyte ratio, and decreased serum albumin were factors associated with severe GI involvement. Frequencies of renal involvement and biopsy-proven nephritis were higher in the severe GI group. The most commonly used medications were corticosteroids (100.0%) in the severe GI group. The maximum corticosteroid dose was higher (2.9 vs. 2.0 mg/kg), and more second-line therapies were needed (30.9% vs. 16.94%) in the severe GI group. Conclusions: Severe GI involvement in children is common in our center. Rare onset age, purpura above the waist, vomiting, high neutrophil-to-lymphocyte ratio, and decreased serum albumin are associated with severe GI involvement. Patients with severe GI involvement need higher doses of corticosteroids and second-line therapy.

20.
Nat Commun ; 14(1): 5246, 2023 08 28.
Artículo en Inglés | MEDLINE | ID: mdl-37640708

RESUMEN

Molecular chaperone HSP70s are attractive targets for cancer therapy, but their substrate broadness and functional non-specificity have limited their role in therapeutical success. Functioning as HSP70's cochaperones, HSP40s determine the client specificity of HSP70s, and could be better targets for cancer therapy. Here we show that tumors defective in HSP40 member DNAJA2 are benefitted from immune-checkpoint blockade (ICB) therapy. Mechanistically, DNAJA2 maintains centrosome homeostasis by timely degrading key centriolar satellite proteins PCM1 and CEP290 via HSC70 chaperone-mediated autophagy (CMA). Tumor cells depleted of DNAJA2 or CMA factor LAMP2A exhibit elevated levels of centriolar satellite proteins, which causes aberrant mitosis characterized by abnormal spindles, chromosome missegregation and micronuclei formation. This activates the cGAS-STING pathway to enhance ICB therapy response in tumors derived from DNAJA2-deficient cells. Our study reveals a role for DNAJA2 to regulate mitotic division and chromosome stability and suggests DNAJA2 as a potential target to enhance cancer immunotherapy, thereby providing strategies to advance HSPs-based cancer therapy.


Asunto(s)
División del Núcleo Celular , Mitosis , Humanos , Cromogranina A , Nucleotidiltransferasas/genética , Inestabilidad Cromosómica , Proteínas HSP70 de Choque Térmico , Proteínas del Choque Térmico HSP40
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