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1.
Front Public Health ; 12: 1420608, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39104885

RESUMO

Introduction: Heatstroke is a serious clinical condition caused by exposure to high temperature and high humidity environment, which leads to a rapid increase of the core temperature of the body to more than 40°C, accompanied by skin burning, consciousness disorders and other organ system damage. This study aims to analyze the effect of meteorological factors on the incidence of heatstroke using machine learning, and to construct a heatstroke forecasting model to provide reference for heatstroke prevention. Methods: The data of heatstroke incidence and meteorological factors in a city in South China from May to September 2014-2019 were analyzed in this study. The lagged effect of meteorological factors on heatstroke incidence was analyzed based on the distributed lag non-linear model, and the prediction model was constructed by using regression decision tree, random forest, gradient boosting trees, linear SVRs, LSTMs, and ARIMA algorithm. Results: The cumulative lagged effect found that heat index, dew-point temperature, daily maximum temperature and relative humidity had the greatest influence on heatstroke. When the heat index, dew-point temperature, and daily maximum temperature exceeded certain thresholds, the risk of heatstroke was significantly increased on the same day and within the following 5 days. The lagged effect of relative humidity on the occurrence of heatstroke was different with the change of relative humidity, and both excessively high and low environmental humidity levels exhibited a longer lagged effect on the occurrence of heatstroke. With regard to the prediction model, random forest model had the best performance of 5.28 on RMSE and dropped to 3.77 after being adjusted. Discussion: The incidence of heatstroke in this city is significantly correlated with heat index, heatwave, dew-point temperature, air temperature and zhongfu, among which the heat index and dew-point temperature have a significant lagged effect on heatstroke incidence. Relevant departments need to closely monitor the data of the correlated factors, and adopt heat prevention measures before the temperature peaks, calling on citizens to reduce outdoor activities.


Assuntos
Golpe de Calor , Aprendizado de Máquina , Conceitos Meteorológicos , Humanos , Golpe de Calor/epidemiologia , Golpe de Calor/etiologia , China/epidemiologia , Incidência , Previsões , Cidades , Temperatura Alta/efeitos adversos , Umidade
2.
Spectrochim Acta A Mol Biomol Spectrosc ; 323: 124933, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39121677

RESUMO

A large number of studies have shown that lysosomal microcircumstances changes can affect many physiological and pathological processes at the cellular level. However, the visual detection of lysosomal microcircumstances is relatively difficult due to low pH (4.5-6.0) value in lysosomal that require the probe not only stable under acidic condition but also has a good localization effect to lysosomal. Obviously, novel fluorescent which possessed both acidic stability and lysosomal-target property together with lysosomal viscosity active is highly demanded. Herein, a novel BODIPY molecular CarBDP based on carbazole group was rationally designed and synthesized for the lysosomal imaging. CarBDP exhibited AIE feature with a large Stokes shift of up to 157 nm. More importantly, co-localization assay of the CarBDP-treated MCF-7 cells indicated that CarBDP has a good localization effect on lysosomal (Rr = 0.7109) due to the carbazole group while the normal BODIPY that without carbazole group (PhBDP) shows poor localization performance, this was the first time that a small molecule can locate lysosomes only based on carbazole group. CarBDP exhibits strong solid emission with long fluorescence decay lifetime (τ = 44.54 ns) and was stable under acid condition.The probe CarBDP assembled with carbazole group was successfully utilized for lysosomal localization and mapping lysosomal viscosity in live cells, which provides a novel candidate tool for the determination of lysosomal microcircumstances.

3.
Eur J Radiol ; 179: 111657, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39163806

RESUMO

OBJECTIVES: To establish and validate a technetium 99m sestamibi (99mTc-MIBI) single-photon emission computed tomography/computed tomography (SPECT/CT) nomogram for predicting non-small cell lung cancer (NSCLC). Comparing the diagnostic performance of early and delayed SPECT/CT nomogram, and compare the diagnostic performance of SPECT/CT radiomics models with single SPECT and CT radiomics models. METHODS: This prospective study included 119 lesions (NSCLC: n = 92, benign pulmonary lesions: n = 27) from 103 patients (mean age: 59.68 ± 8.94 years). Patients underwent dual-phase 99mTc-MIBI SPECT/CT imaging. They were divided into the training (n = 83) and validation (n = 36) cohorts. Logistic regression, support vector machine, random forest, and light-gradient boosting machine were applied to train and determine the optimal machine learning model. Then, combining radiomics score and clinical factors, establish nomograms for diagnosing NSCLC. RESULT: CYFRA21-1 was selected for constructing the clinical model. In early imaging, the areas under the curve (AUCs) of the clinical model, radiomics model, and nomogram were 0.571, 0.830, and 0.875, respectively. The nomogram performed better than the clinical model and similarly to the radiomics model (P=0.020, P=0.216), and there are no statistically significant differences in the predictive performance between the radiomics model and the clinical model (P=0.103). In delayed imaging, the AUC was 0.643, 0.888, and 0.893, respectively. The predictive performance of the nomogram was superior compared to the clinical model and comparable to the radiomics model (P=0.042, P=0.480), and the radiomics model also demonstrated superior diagnostic performance compared to the clinical model (P=0.049). Compared to early SPECT/CT results, the AUC values of the nomogram and radiomics models in the delayed phase were higher, although no statistical differences were found (P=0.831, P=0.568). In delayed imaging, the AUC of the radiomics models for CT and SPECT was 0.696 and 0.768, respectively, SPECT/CT radiomics exhibited significant differences compared with CT and SPECT alone (P=0.042, P=0.038). CONCLUSION: Dual-phase 99mTc-MIBI SPECT/CT nomograms and radiomics models can effectively predict NSCLC, providing an economically and non-invasive imaging method for diagnosing NSCLC, moreover, these findings provide a basis for early diagnosis and treatment strategies in NSCLC patients. Delayed-phase SPECT/CT imaging may offer greater practical value than early-phase imaging for diagnosing NSCLC. However, this novel approach necessitates further validation in larger, multi-center cohorts. CLINICAL RELEVANCE: Radiomics nomogram based on SPECT/CT for discriminating NSCLC from benign lung lesions helps to aid early diagnosis and guide treatment. KEY POINTS: Nomograms, based on dual-phase SPECT/CT, was constructed to discriminate between non-small cell lung cancer and benign lesions. SPECT/CT radiomics model has better predictive performance than SPECT and CT radiomics model.

4.
J Reprod Immunol ; 165: 104312, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39094215

RESUMO

BACKGROUND: Endometriosis (EMs) is a chronic disease characterized by endometrial-like tissue present outside of the uterus. Macrophages have been confirmed to participate in the development of EMs. Integrin ß3 (ITGB3), a ß-subunit of the integrin family, is crucial in tumor progression. In this study, we investigated the pivotal role of ITGB3 in endometrial stromal cells (ESCs) and its influence on the development of EMs, particularly focusing on the regulatory impact of macrophages. METHODS: In this study, we used western blot, Real-time qPCR, Immunohistochemistry to detected the high expression of ITGB3 in ESCs. ITGB3-overexpression ESCs (ITGB3-OE) was constructed and detected by RNA-seq with normal ESCs. ATP and lactate expression assay, transwell migration assay, wound healing, cell adhesion assay and other molecular biology techniques were used to explore the potential mechanisms. In vivo, we constructed the EMs mouse model and injected with cilengitite to inhibit ITGB3. RESULTS: Here, we found ITGB3 highly expressed in ectopic lesions in EMs. The increasing ITGB3 resulted in activating the glycolysis, which produced more ATP and lactate in ITGB3-OE. After culturing with lactate, the migration, proliferation and invasion ability of ESCs were enhanced, while the result in 2-DG was reversed. In vivo, the results showed that after antagonizing ITGB3, the number of ectopic lesions was decrease. CONCLUSIONS: Our findings indicate that ITGB3 up-regulated by macrophages are able to regulate the glycolysis to promote the development of EMs and lactate enhances the ability of proliferation, migration, invasion and adhesion of EMs iv vivo and in vitro.

5.
Minerva Anestesiol ; 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39104227

RESUMO

BACKGROUND: Opioids are the main analgesic drugs used in the perioperative period, but they often have various adverse effects. Recent studies have shown that quadratus lumborum block (QLB) has an opioid sparing effect. The aim of this study was to further evaluate the effect of opioid-free anesthesia (OFA) combined with regional block on the quality of recovery in patients undergoing retroperitoneoscopic renal surgery. METHODS: Sixty patients undergoing elective retroperitoneoscopic renal surgery were divided into the opioid-free anesthesia with quadratus lumborum block group (OFA group, N.=30) and opioid anesthesia with quadratus lumborum block group (OA group, N.=30) using the random number table method. The main outcome measures were the quality of recovery assessed by Quality of Recover-40 (QoR-40) at the 24th postoperative hour. Secondary outcomes were postoperative pain score, postoperative opioid consumption, postoperative nausea and vomiting, time to ambulate, and time to readiness for discharge. RESULTS: The QoR-40 score on the first postoperative day was significantly higher in the OFA group than that in the OA group (175.41±6.74 vs. 165.07±4.55; P<0.05). OFA also significantly reduced postoperative pain (P<0.05) and morphine consumption at both the 24th and 48th postoperative hour (P<0.05), as well as time to ambulate, and time to readiness for discharge (P<0.05). CONCLUSIONS: OFA with regional block is superior to opioid anesthesia with regional block in the quality of recovery after retroperitoneiscopic renal surgery.

6.
Mucosal Immunol ; 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39097147

RESUMO

Period circadian clock 2 (PER2) is involved in the pathogenesis of various inflammatory and autoimmune diseases. However, there are gaps in our understanding of the role of PER2 in regulating CD4+ T cells beyond its time-keeping function in ulcerative colitis (UC) pathogenesis. Our findings revealed PER2 was predominantly expressed in CD4+ T cells, while it was significantly decreased in the inflamed mucosa and peripheral blood CD4+ T cells of UC patients compared with that in Crohn's disease (CD) patients and healthy controls (HC). Notably, PER2 expression was significantly recovered in UC patients in remission (R-UC) compared to that in active UC patients (A-UC) but not in CD patients. It was negatively correlated with the Ulcerative Colitis Endoscopic Index of Severity (UCEIS), Crohn's Disease Activity Index (CDAI), Simple Endoscopic Score for Crohn's disease (SES-CD), and C-reactive protein (CRP), respectively. Overexpression of PER2 markedly inhibited IFN-γ production in UC CD4+ T cells. RNA-seq analysis showed that overexpression of PER2 could repress the expression of a disintegrin and metalloproteinase 12 (ADAM12), a costimulatory molecule that determines Th1 cell fate. Mechanistically, cleavage under targets and tagmentation (CUT&Tag) analysis revealed that PER2 down-regulated ADAM12 expression by reducing its binding activity, thereby suppressing IFN-γ production in UC CD4+ T cells. Additionally, our data further demonstrated that ADAM12 was upregulated in CD4+ T cells and inflamed mucosa of A-UC patients compared to HC. Our study reveals a critical role of PER2 in regulating CD4+ T cell differentiation and highlights its potential as a therapeutic target for UC treatment.

7.
J Colloid Interface Sci ; 677(Pt B): 675-682, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39159522

RESUMO

The urgent need to develop efficient, durable, and cost-effective oxygen evolution reaction (OER) catalysts for energy conversion and storage has prompted extensive research. Currently available commercial noble metal-based OER catalysts are expensive and exhibit limited long-term stability. In this study, boron-doped diamond composites (BDDCs) consisting of CoFe and CoFe2C nanoparticles supported by boron-doped diamond (BDD) particles have been prepared. The BDDC catalyst, prepared through a straightforward annealing process, exhibits exceptional durability (up to 72 h at 10 mA cm-2), a low overpotential (306 mV at 10 mA cm-2), and modest Tafel slope (58 mV dec-1). The coherent interfaces between CoFe/CoFe2C nanoparticles and the BDD substrate are essential for enhancing the OER performance. The fabrication method and composite structures presented in this study may facilitate the design and production of promising catalysts.

8.
mSystems ; : e0063624, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39120143

RESUMO

Cats (Felidae) have become an integral part of many households. However, our understanding of the full spectrum of pathogens affecting cats (referred to as the infectome) is limited, mainly due to the inadequacy of commonly used diagnostic tools in capturing the complete diversity of potential pathogens and the prevalence of pathogen co-infections. In this study, we employed a meta-transcriptomic approach to simultaneously characterize the infectome contributing to different disease syndromes and to investigate spatial, demographic, and ecological factors influencing pathogen diversity and community composition in a cohort of 27 hospitalized cats and seven stray cats. We identified 15 species of pathogens, with Candidatus Rickettsia tarasevichiae and Tritrichomonas foetus representing potential spillover risks. Importantly, although most cases of ascites hyperplasia were explained by coinfection with multiple pathogens, we identified the potential novel clinical outcomes of M. aubagnense infection among cats. We demonstrated that the increase in infectome diversity can be explained by a variety of predictors including age growth, temperature increase, and a higher proportion of females, with age growth presenting the strongest effect. Fine-scale analysis indicated that a higher diversity of infectomes were harbored in young cats rather than adult ones. Our results demonstrated that most feline diseases are better explained by the presence of virus-bacteria or virus-virus coinfection. This study serves as a timely endorsement for clinical diagnosis by vets to consider the cause of a disease based on a panel of cryptical co-infecting pathogens rather than on individual infectious agents. IMPORTANCE: Frequent studies reported the risks of cats as an intermediate host of zoonotic pathogens (e.g., SARS-CoV-2). Cats have a physically close interaction with their owners through activities like petting, kissing, and being licked on the cheek and hands. However, there are still limited studies that systematically investigate the infectome structure of cats. In this study, we employed a meta-transcriptomics approach to characterize 15 species of pathogens in cats, with Candidatus Rickettsia tarasevichiae first characterizing infection in diseased cats. Most feline diseases were better explained by the presence of virus-bacteria or virus-virus coinfection. The increase in infectome diversity could be influenced by a variety of predictors including age growth, temperature increase, and a higher proportion of females. A higher diversity of pathogens was harbored in young cats rather than adults. Importantly, we showed the value of linking the modern influx of meta-transcriptomics with comparative ecology and demography and of utilizing it to affirm that ecological and demographic variations impact the total infectome.

9.
Lung Cancer ; 194: 107888, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39043077

RESUMO

OBJECTIVE: To investigate the effects of pregabalin combined with tramadol/paracetamol on acute pain in patients with CT-guided puncture localization of pulmonary nodules. MATERIALS AND METHODS: In this randomized, placebo-controlled and single-center study, 120 patients were allocated randomly to four groups: the control group (Group P), the pregabalin-placebo group (Group BP), the tramadol/paracetamol-placebo group (Group AP), and the pregabalin-tramadol/paracetamol group (Group AB). The primary outcome was the NRS (Numerical Rating Scale) score. Other outcomes included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), pulse oxygen saturation (SpO2), the incidence of moderate to severe pain, the analgesia recovery ratio, the incidence of adverse drug reactions and patients' satisfaction. RESULTS: No significant interaction was detected between the interventions (P = 0.752). The NRS score of the Taking pregabalin group and the Taking tramadol/paracetamol group were significantly lower than those of the Not-taking pregabalin group and the Not-taking tramadol/paracetamol group respectively (P < 0.05). There was significant difference in the NRS scores among the four groups (P < 0.001). The NRS score of Group AB was significantly lower than that of Group P (P < 0.001), Group BP (P < 0.001) and Group AP (P = 0.001). At the same time, the NRS scores of Group BP (P < 0.001) and Group AP (P < 0.001) were significantly lower than those of Group P, but there was no significant difference between Group BP and Group AP (P = 1.000). The SBP, DBP, HR, the incidence of moderate to severe pain and the analgesia recovery ratio of Group AB were significantly lower than those of Group P (P < 0.05), while the SpO2 and the number of people who were very satisfied were significantly higher than those of Group P (P < 0.05). There was no significant difference in the incidence of adverse drug reactions among the four groups (P = 0.272). CONCLUSIONS: The combination or single use of pregabalin and tramadol/paracetamol can effectively relieve the acute pain after localization. Pregabalin combined with tramadol/paracetamol has the best analgesic effect and significantly reduces the hemodynamic fluctuations, with high safety and low incidence of adverse drug reactions, which has a certain clinical popularization and application value.


Assuntos
Acetaminofen , Dor Aguda , Pregabalina , Tomografia Computadorizada por Raios X , Tramadol , Humanos , Tramadol/administração & dosagem , Tramadol/uso terapêutico , Tramadol/efeitos adversos , Pregabalina/uso terapêutico , Pregabalina/administração & dosagem , Pregabalina/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Acetaminofen/administração & dosagem , Acetaminofen/uso terapêutico , Acetaminofen/efeitos adversos , Dor Aguda/tratamento farmacológico , Dor Aguda/etiologia , Dor Aguda/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Idoso , Quimioterapia Combinada , Adulto , Neoplasias Pulmonares/tratamento farmacológico , Analgésicos/administração & dosagem , Analgésicos/uso terapêutico , Analgésicos/efeitos adversos , Punções/efeitos adversos , Punções/métodos , Resultado do Tratamento , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/uso terapêutico , Manejo da Dor/métodos , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/tratamento farmacológico , Nódulo Pulmonar Solitário/patologia , Medição da Dor
10.
BMC Pulm Med ; 24(1): 326, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38970041

RESUMO

BACKGROUND: To investigate the associations of different combinations of moderate to vigorous physical activity (MVPA) and muscle strengthening activity (MSA) with all-cause and cancer mortality among lung cancer survivors. METHODS: This nationwide prospective cohort study used data from the US National Health Interview Survey 2009-2018. A total of 785 lung cancer survivors were included in the study. Participants were linked to the National Death Index through December 31, 2019. Self-reported MVPA and MSA frequency data were used to obtain 4 mutually exclusive exposure categories. Multivariate Cox proportional hazard models were applied to explore the association between exposure categories and outcomes. RESULTS: The mean (standard deviation [SD]) age of the study population was 69.1 (11.3) years and 429 (54.6%) were female. Among them, 641 (81.7%) were White and 102 (13.0%) were Black. The median follow-up time was 3 years (2526 person-years), and 349 (44.5%) all-cause deaths and 232 (29.6%) cancer deaths occurred. Compared to the MVPA < 60 min/week and MSA < 2 sessions/week group, individuals in the MVPA ≥ 60 min/week and MSA < 2 sessions/week group showed hazard ratios (HRs) of 0.50 (95% CI, 0.36-0.69) for all-cause mortality and 0.37 (95% CI, 0.20-0.67) for cancer mortality after the adjustment of covariates. Those in the MVPA ≥ 60 min/week and MSA ≥ 2 sessions/week group exhibited HRs of 0.52 (95% CI, 0.35-0.77) for all-cause mortality and 0.27 (95% CI, 0.12-0.62) for cancer mortality when compared to the MVPA < 60 min/week and MSA < 2 sessions/week group. We also identified distinct non-linear relationships between MVPA and outcomes risk among two MSA frequency subgroups. CONCLUSION: This cohort study demonstrated that higher levels of MVPA and MSA combined might be associated with optimal reductions of mortality risk in lung cancer survivors.


Assuntos
Sobreviventes de Câncer , Exercício Físico , Neoplasias Pulmonares , Humanos , Feminino , Masculino , Idoso , Neoplasias Pulmonares/mortalidade , Pessoa de Meia-Idade , Sobreviventes de Câncer/estatística & dados numéricos , Estudos Prospectivos , Estados Unidos/epidemiologia , Modelos de Riscos Proporcionais , Treinamento Resistido , Força Muscular , Causas de Morte
11.
Plant J ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38990506

RESUMO

The osmotic resistance mechanism has been extensively studied in whole plants or plant tissues. However, little is known about it in embryogenic tissue (ET) which is widely used in plant-based biotechnological systems. Suberin, a cell wall aliphatic and aromatic heteropolymer, plays a critical role in plant cells against osmosis stress. The suberin regulatory biosynthesis has rarely been studied in gymnosperms. Here, PaMYB11, a subgroup 11 R2R3-MYB transcription factor, plays a key role in the osmotic resistance of Norway spruce (Picea abies) ETs during cryoprotectant pretreatment. Thus, RNA-seq, histological, and analytical chemical analyses are performed on the stable transformations of PaMYB11-OE and PaMYB11-SRDX in Norway spruce ETs. DAP-seq, Y1H, and LUC are further combined to explore the PaMYB11 targets. Activation of PaMYB11 is necessary and sufficient for suberin lamellae deposition on Norway spruce embryogenic cell walls, which plays a decisive role in ET survival under osmotic stress. Transcriptome analysis shows that PaMYB11 enhances suberin lamellae monomer synthesis by promoting very long-chain fatty acid (VLCFA) synthesis. PaPOP, PaADH1, and PaTET8L, the first two (PaADH1 and PaPOP, included) involved in VLCFA synthesis, are proved to be the direct targets of PaMYB11. Our study identified a novel osmotic response directed by PaMYB11 in Norway spruce ET, which provides a new understanding of the resistance mechanism against osmosis in gymnosperms.

12.
RSC Adv ; 14(32): 23322-23331, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39049885

RESUMO

Nanofluid application in enhanced oil recovery (EOR) recently emerged and garnered significant attention within the field. Nanofluids possess unique properties of reducing oil-water interfacial tension, stabilizing emulsions, altering rock surface wettability, and enhancing disjoining pressure between crude oil and rock surfaces, therefore have potential for the oil recovery process. This review provides an in-depth exploration of various aspects related to nanofluids in EOR. Different types of nanofluids are presented with their preparation methods and representative properties. More importantly, the disjoining pressure, a key physical concept in nanofluid-assisted EOR, is introduced and discussed in terms of the mechanism of oil displacement and measurement methods. Further understanding the role of disjoining pressure in nanofluid-assisted oil displacement is necessary for the development and application of effective nanofluids for EOR.

13.
Food Sci Nutr ; 12(7): 5100-5110, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39055233

RESUMO

Our previous clinical metabolomics study illustrated that energy metabolism disorder is an underlying pathogenesis mechanism for the development of alcoholic liver disease (ALD). Supplementation of nicotinamide (NAM), the precursor of nicotinamide adenine dinucleotide (NAD+), may restore the energy metabolism homeostasis of ALD and thus serves as potential therapeutics to treat ALD. In this bedside-to-bench study, the protective effect of NAM against ALD was investigated by using the NIAAA mice model (chronic-plus-binge ethanol), and the liver regeneration boosting capability of NAM was evaluated by the partial hepatectomy mice model. Our results showed that NAM supplements not only protected the liver from alcohol-induced injury and improved alcohol-induced mitochondrial structure and function change, but also boosted liver regeneration in postpartial hepatectomy mice by increasing liver NAD+ content. These findings suggested that NAM, a water-soluble form of vitamin B3, can promote liver regeneration and improves liver function by alleviating alcohol-induced energy metabolism disorder.

14.
Chin Med J (Engl) ; 137(15): 1823-1834, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-38973237

RESUMO

BACKGROUND: Heterotaxy (HTX) is a thoracoabdominal organ anomaly syndrome and commonly accompanied by congenital heart disease (CHD). The aim of this study was to analyze rare copy number variations (CNVs) in a HTX/CHD cohort and to examine the potential mechanisms contributing to HTX/CHD. METHODS: Chromosome microarray analysis was used to identify rare CNVs in a cohort of 120 unrelated HTX/CHD patients, and available samples from parents were used to confirm the inheritance pattern. Potential candidate genes in CNVs region were prioritized via the DECIPHER database, and PNPLA4 was identified as the leading candidate gene. To validate, we generated PNPLA4 -overexpressing human induced pluripotent stem cell lines as well as pnpla4 -overexpressing zebrafish model, followed by a series of transcriptomic, biochemical and cellular analyses. RESULTS: Seventeen rare CNVs were identified in 15 of the 120 HTX/CHD patients (12.5%). Xp22.31 duplication was one of the inherited CNVs identified in this HTX/CHD cohort, and PNPLA4 in the Xp22.31 was a candidate gene associated with HTX/CHD. PNPLA4 is expressed in the lateral plate mesoderm, which is known to be critical for left/right embryonic patterning as well as cardiomyocyte differentiation, and in the neural crest cell lineage. Through a series of in vivo and in vitro analyses at the molecular and cellular levels, we revealed that the biological function of PNPLA4 is importantly involved in the primary cilia formation and function via its regulation of energy metabolism and mitochondria-mediated ATP production. CONCLUSIONS: Our findings demonstrated a significant association between CNVs and HTX/CHD. Our data strongly suggested that an increased genetic dose of PNPLA4 due to Xp22.31 duplication is a disease-causing risk factor for HTX/CHD.


Assuntos
Aciltransferases , Variações do Número de Cópias de DNA , Cardiopatias Congênitas , Lipase , Animais , Feminino , Humanos , Masculino , Cromossomos Humanos X/genética , Variações do Número de Cópias de DNA/genética , Cardiopatias Congênitas/genética , Síndrome de Heterotaxia/genética , Lipase/genética , Peixe-Zebra/genética
15.
J Pharm Biomed Anal ; 249: 116333, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39002187

RESUMO

The pollution of mycotoxins to crops such as traditional Chinese medicines (TCMs) is an established problem throughout the world. Thus, mycotoxin determination in TCMs during production and processing is significantly necessary, which means rapid, sensitive and accurate analytical methods are needed. In this work, a new method of visual protein microarray based on a 96-well microtiter plate was proposed. Combined with a colorimetric method, five mycotoxins (ochratoxin A, zearalenone, deoxynivalenol, aflatoxin B1 and fumonisin B1) in 90 samples (TCMs) could be detected simultaneously within 30 minutes. The detection limits for the five mycotoxins are 0.25 µg/kg, 0.33 µg/kg, 11.84 µg/kg, 0.06 µg/kg, and 3.58 µg/kg, which can satisfy specified requirements of mycotoxins in the Chinese Pharmacopoeia (2020 edition) adequately. Under repeated conditions, experiments were carried out on actual samples to verify the feasibility of the method. The results showed that the recoveries of all analytes were between 70 % and 120 %, and the relative standard deviations were less than 15 %. In comparison to LC-MS/MS, this method significantly reduces the required time, and the colorimetric technique offers more direct results compared to fluorescence-based screening assays. This method exhibits substantial potential for the rapid and sensitive on-site detection of TCMs for quality control.


Assuntos
Colorimetria , Contaminação de Medicamentos , Medicamentos de Ervas Chinesas , Limite de Detecção , Micotoxinas , Análise Serial de Proteínas , Micotoxinas/análise , Análise Serial de Proteínas/métodos , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/química , Contaminação de Medicamentos/prevenção & controle , Colorimetria/métodos , Medicina Tradicional Chinesa , Espectrometria de Massas em Tandem/métodos
16.
Sci Rep ; 14(1): 16142, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38997316

RESUMO

Agriculture water use accounts for 70% of the total water withdrawal worldwide. The evapotranspiration during crop growth is one of the important hydrological processes in the agricultural water cycle. This study proposed the concept of artificial irrigation evapotranspiration of irrigated crops to describe that the evapotranspiration caused by irrigation water use. Irrigated crops rely on two kinds of water sources: precipitation and irrigation water. With the construction of irrigation schemes, the artificial irrigation evapotranspiration plays an increasingly important role in the dualistic water cycle system of irrigated cropland. To reveal the amount of artificial irrigation evapotranspiration of 17 categories of irrigated crops in China, this study proposed a new quantitative model system which was established based on traditional evapotranspiration models and soil water balance models. Based on the new model system, we calculated the annual artificial irrigation evapotranspiration of irrigated crops for the period 2013 to 2017 in China. The results showed that the proportion of artificial irrigation evapotranspiration to the total evapotranspiration of irrigated crops was 41.3%, whose value was 228.1 km3 a-1. The artificial irrigation evapotranspiration in different agricultural water management regions were 90.0 km3 a-1 in the northeast region, 86.0 km3 a-1 in the southeast region, and relatively low 52.2 km3a-1 in the west region. The results of this study can provide methods for water management and policy-making in agricultural irrigated areas, and it can also provide a preliminary understanding of the influence of human activities on the dualistic water cycle in cropland.

17.
Angew Chem Int Ed Engl ; : e202407116, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38934207

RESUMO

The vast number of element combinations and the explosive growth of composition space pose significant challenges to the development of high-entropy alloys (HEAs). Here, we propose a procedural research method aimed at accelerating the discovery of efficient electrocatalysts for oxygen reduction reaction (ORR) based on Pt-based quinary HEAs. The method begins with an element library provided by a large language model (LLM), combined with microscale precursor printing and pulse high-temperature synthesis techniques to prepare multi-element combination HEA array in one step. Through high-throughput measurement using scanning electrochemical cell microscopy (SECCM), precise identification of highly active HEA element combinations and exploration of composition space for a specific combination are achieved. Advantageous element combinations are further validated in practical electrocatalytic evaluations. The contributions of individual element sites and the synergistic effects among elements of such HEAs in enhancing reaction activity are elucidated via density functional theory (DFT) calculations. This method integrates high-throughput experiments, practical catalyst validation, and DFT calculations, providing a new pathway for accelerating the discovery of efficient multi-element materials in the field of energy catalysis.

18.
Hosp Pharm ; 59(4): 465-470, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38919762

RESUMO

Background: Poison centers develop triage threshold guidelines for pediatric metformin ingestions. Our network uses 1700 mg, or 85 mg/kg. Objective: To describe the dose, clinical course, and outcomes for inadvertent metformin ingestions in children 5 years old and younger reported to our statewide poison center network. Methods: We searched the poison center database 2011 to 2021 for metformin ingestions in patients 5 years and younger. Variables included age, sex, weight, dose, symptoms, outcome, and more. We used descriptive statistics with medians and interquartile ranges (IQR) for continuous variables. Results: Of 669 cases, exposures by age were 208 (31.1%) 1 to 2 years, and 275 (41.1%) 2 years. Weight was recorded in 342 (51.1%) (median 13.5 kg; IQR: 3.7 kg), and dose in 149 (22.3%) (median 500 mg; IQR: 500 mg). Milligram/kilogram values were available for 103 (15.4%) with median 42.4 mg/kg, IQR: 39 mg/kg. Most (647, 98.5%) exposures were unintentional. Most (445/669, 66.5%) were managed at a non-healthcare facility, while 204 (30.7%) were already at or referred to a healthcare facility. Of these 204 patients, 169 (82.8%) were evaluated and treated at the emergency department and discharged. Four (2%) were admitted to critical care, and 7 (3.4%) to the ward. Medical outcomes by effect were 5 (0.7%) minor, 2 (0.3%) moderate, 253 (37.8%) none, 292 (43.6%) not followed (minimal effects possible), and no major effects or deaths. Of 20 clinical occurrences reported, vomiting was most common (8, 1.2%). Conclusion: Despite little recorded dosage information, pediatric metformin ingestions under 85 mg/kg had predominantly uneventful medical outcomes.

19.
Exp Brain Res ; 242(8): 1957-1970, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38918211

RESUMO

The purpose of the present study was to elucidate whether an external reference frame contributes to tactile localization in blindfolded healthy humans. In a session, the right forearm was passively moved until the elbow finally reached to the target angle, and participants reached the left index finger to the right middle fingertip. The locus of the right middle fingertip indicated by the participants deviated in the direction of the elbow extension when vibration was provided to the biceps brachii muscle during the passive movement. This finding indicates that proprioception contributes to the identification of the spatial coordinate of the specific body part in an external reference frame. In another session, the tactile stimulus was provided to the dorsal of the right hand during the passive movement, and the participants reached the left index finger to the spatial locus at which the tactile stimulus was provided. Vibration to the biceps brachii muscle did not change the perceived locus of the tactile stimulus indicated by the left index finger. This finding indicates that an external reference frame does not contribute to tactile localization during the passive movement. Humans may estimate the spatial coordinate of the tactile stimulus based on the time between the movement onset and the time at which the tactile stimulus is provided.


Assuntos
Propriocepção , Percepção do Tato , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Percepção do Tato/fisiologia , Propriocepção/fisiologia , Vibração , Tato/fisiologia , Músculo Esquelético/fisiologia , Dedos/fisiologia , Movimento/fisiologia , Percepção Espacial/fisiologia , Estimulação Física
20.
Life Sci ; 352: 122877, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38942358

RESUMO

AIMS: The study evaluated the antiviral effect of Verapamil against respiratory syncytial virus (RSV) and investigated its underlying mechanism. MATERIALS AND METHODS: RSV-infected BALB/c mice were treated with Verapamil. Body weight, survival rates, viral load, lung damage, inflammatory factors, and the expression of RSV fusion (F) protein were analyzed. In cellular studies, intracellular Ca2+ and viral titers were measured in the presence of Verapamil, Calcium Chloride, and EGTA. A time-of-addition assay assessed the antiviral effect of Verapamil. KEY FINDINGS: Mice infected with RSV and treated with Verapamil exhibited a significant decrease in weight loss, an increase in survival rates, and reductions in viral titers, RSV F protein expression, inflammatory responses, and lung tissue injury. Verapamil reduced intracellular calcium levels, which correlated with reduced viral titers. The addition of calcium chloride reversed the anti-viral effects mediated by Verapamil, while EGTA potentiated them. The antiviral activity of Verapamil was observed during the early phase of RSV infection, likely by blocking Ca2+ channels and inhibiting virus replication. SIGNIFICANCE: Verapamil effectively inhibits RSV infection by blocking calcium channels and reducing intracellular calcium levels, thereby impeding viral replication. Thus, Verapamil shows promise as a treatment for RSV.


Assuntos
Antivirais , Cálcio , Camundongos Endogâmicos BALB C , Infecções por Vírus Respiratório Sincicial , Verapamil , Verapamil/farmacologia , Animais , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/virologia , Infecções por Vírus Respiratório Sincicial/metabolismo , Cálcio/metabolismo , Camundongos , Antivirais/farmacologia , Feminino , Replicação Viral/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/farmacologia , Humanos , Carga Viral/efeitos dos fármacos , Vírus Sinciciais Respiratórios/efeitos dos fármacos , Pulmão/virologia , Pulmão/metabolismo , Pulmão/efeitos dos fármacos
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