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1.
Cell Death Dis ; 12(4): 362, 2021 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-33824276

RESUMEN

Adhesion G protein-coupled receptor A1 (ADGRA1, also known as GPR123) belongs to the G protein-coupled receptors (GPCRs) family and is well conserved in the vertebrate lineage. However, the structure of ADGRA1 is unique and its physiological function remains unknown. Previous studies have shown that Adgra1 is predominantly expressed in the central nervous system (CNS), indicating its important role in the transduction of neural signals. The aim of this study is to investigate the central function of Adgra1 in vivo and clarify its physiological significance by establishing an Adgra1-deficient mouse (Adgra1-/-) model. The results show that Adgra1-/- male mice exhibit decreased body weight with normal food intake and locomotion, shrinkage of body mass, increased lipolysis, and hypermetabolic activity. Meanwhile, mutant male mice present elevated core temperature coupled with resistance to hypothermia upon cold stimulus. Further studies show that tyrosine hydroxylase (TH) and ß3-adrenergic receptor (ß3-AR), indicators of sympathetic nerve excitability, are activated as well as their downstream molecules including uncoupling protein 1 (UCP1), coactivator 1 alpha (PGC1-α) in brown adipose tissue (BAT), and hormone-sensitive lipase (HSL) in white adipose tissue (WAT). In addition, mutant male mice have higher levels of serum T3, T4, accompanied by increased mRNAs of hypothalamus-pituitary-thyroid axis. Finally, Adgra1-/- male mice present abnormal activation of PI3K/AKT/GSK3ß and MEK/ERK pathways in hypothalamus. Overexpression of ADGRA1 in Neuro2A cell line appears to suppress these two signaling pathways. In contrast, Adgra1-/- female mice show comparable body weight along with normal metabolic process to their sex-matched controls. Collectively, ADGRA1 is a negative regulator of sympathetic nervous system (SNS) and hypothalamus-pituitary-thyroid axis by regulating PI3K/AKT/GSK3ß and MEK/ERK pathways in hypothalamus of male mice, suggesting an important role of ADGRA1 in maintaining metabolic homeostasis including energy expenditure and thermogenic balance.

2.
J Environ Manage ; 289: 112503, 2021 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-33823415

RESUMEN

Carbon dioxide (CO2) and methane (CH4) produced by denitrification bioreactors in processing agricultural surface runoff have contributed to increasing proportion of greenhouse gases (GHG) emissions. It is the first time to monitor and quantify the emission flux of CO2 and CH4 produced by laboratory-scale denitrification bioreactors which recycled waste Cunninghamia lanceolata sawdust (CLS) and industrial sludge (IS) as fillers to process simulated agricultural surface runoff. Sludge-water ratio, inflow rate and water flow direction are used as experimental factors to study the effect on the emission flux of CO2 and CH4. Results show that emission flux of CO2 from denitrification bioreactors with different sludge-water ratio approached 20 mg m-2h-1, simultaneously the average emission flux of CH4 produced by all bioreactors was 1.785 mg m-2h-1. The addition of sludge increased the emission flux of CH4 and had no significant effect on the emission flux of CO2. Increasing the inflow rate reduced the CO2 emission flux from 21.57 to 1.27 mg m-2h-1, and at the same time increased the CH4 emission flux from 0.007 to 9.54 mg m-2h-1. The gravity flow of wastewater reduced the emission flux of CO2 and CH4. The emissions of CO2 and CH4 from folded plate denitrification bioreactor with CLS and industrial sludge with a volume ratio of 1:2 can be reduced by 24.67% and 73.3%, respectively. There was no need to add special gas collection and treatment devices because CO2 and CH4 emission fluxes produced by the folded plate denitrification bioreactor and gravity denitrification bioreactor are not enough to increase the greenhouse effect. This study quantified the CO2 and CH4 produced by denitrification bioreactors filling CLS and IS, and provided a reference for future research on the gases produced by the denitrification process.

3.
Diagn Cytopathol ; 2021 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-33750018

RESUMEN

Rhabdomyosarcoma (RMS) originates from a differentiation block in muscle progenitors. Leptomeningeal metastasis is a rare but devastating complication of RMS which can be caused by dissemination of cancer cells in cerebrospinal fluid (CSF). Here, we present a 4-year-old female with RMS originating from the upper nasal wall. The following histologic and immunohistochemistry analyses combined with molecular testing analysis supported the diagnosis of embryonal rhabdomyosarcoma (ERMS). Results from CSF routine test, magnetic resonance imaging scans and CSF cytology indicated metastatic meningitis, thus confirming the diagnosis of metastatic ERMS in CSF. This is the first report to describe the clinical features of ERMS in CSF.

4.
Int J Biol Macromol ; 179: 136-143, 2021 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-33667555

RESUMEN

Scalloped (Sd) is transcription factor that regulates cell proliferation and organ growth in the Hippo pathway. In the present research, LmSd was identified and characterized, and found to encode an N-terminal TEA domain and a C-terminal YBD domain. qRT-PCR showed that the LmSd transcription level was highest in the fifth-instar nymphs and very little was expressed in embryos. Tissue-specific analyses showed that LmSd was highly expressed in the wing. Immunohistochemistry indicated that LmSd was highly abundant in the head, prothorax, and legs during embryonic development. LmSd dsRNA injection resulted in significantly down-regulated transcription and protein expression levels compared with dsGFP injection. Gene silencing of LmSd resulted in deformed wings that were curved, wrinkled, and failed to fully expand. Approximately 40% of the nymphs had wing pads that were not able to close normally during molting from fifth-instar nymphs into adults. After silencing of LmSd, the transcription levels of cell division genes were suppressed and the expression levels of apoptosis genes were significantly up-regulated. Our results reveal that LmSd plays an important role in wing formation and development by controlling cell proliferation and inhibiting apoptosis.

5.
PLoS Negl Trop Dis ; 15(3): e0009201, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33725010

RESUMEN

BACKGROUND: This study reviews the progress of leprosy elimination in Yunnan, China, over the past 30 years and identifies the challenges for the next stage of the program. METHODOLOGY/PRINCIPAL FINDINGS: Data were collected from the Leprosy Management Information System in China (LEPMIS). The progress made in the elimination of leprosy between 1990 and 2019 was measured. We defined two time periods, time period 1 (1990-2003) and time period 2 (2004-2019), because multidrug therapy (MDT) was launched for the treatment of leprosy in 1990 and a special fund from the central government was established for leprosy in 2004. During the past 30 years, the number of newly detected leprosy patients in Yunnan has steadily declined. In total, 703 newly detected leprosy patients were reported in 1990, and 353 and 136 cases were reported at the end of 2003 and 2019, respectively. At the end of 1990, 90.7% (117/129) of counties in Yunnan Province were identified as leprosy-endemic counties (>1 case per 100,000 population). By the end of 2003 and 2019, 39.3% (46/117) and 85.5% (100/117) of the leprosy-endemic counties, respectively, had dropped below the elimination threshold. The main challenges are the remaining leprosy-endemic counties, the high rate of cases with a contact history, insufficient early detection, and leprosy cases resulting in physical disability. CONCLUSIONS/SIGNIFICANCE: A multifaceted strategy for leprosy elimination in Yunnan Province has been successfully implemented, and remarkable progress has been made in the elimination of leprosy in this area. The priorities for leprosy elimination in the next stage are securing sustainable support and investment from the government, establishing an effective surveillance system, ensuring prompt early detection, providing treatment with MDT, preventing transmission of M. leprae, preventing disability, providing health education, and preventing recurrence of the epidemic situation of leprosy.

6.
Inflamm Bowel Dis ; 2021 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-33772551

RESUMEN

Ulcerative colitis (UC) is an idiopathic, long-term inflammatory disorder of the colon, characterized by a continuous remitting and relapsing course. The intestinal mucus barrier is the first line at the interface between the host and microbiota and acts to protect intestinal epithelial cells from invasion. Data from patients and animal studies have shown that an impaired mucus barrier is closely related to the severity of UC. Depletion of the mucus barrier is not just the strongest but is also the only independent risk factor predicting relapse in patients with UC. Peroxisome proliferator-activated receptor gamma (PPARγ), a nuclear transcription regulator, is involved in the regulation of inflammatory cytokine expression. It is also known to promote mucus secretion under pathological conditions to expel pathogenic bacteria or toxins. More important, PPARγ has been shown to affect host-microbiota interactions by modulating the energy metabolism of colonocytes and the oxygen availability of the intestinal microbiome. It is well known that gut microbiota homeostasis is essential for butyrate generation by the commensal bacteria to supply energy resources for colonocytes. Therefore, it can be speculated that PPARγ, as a central coordinator of the mucus barrier, may be a promising target for the development of effective agents to combat UC.

7.
Ying Yong Sheng Tai Xue Bao ; 32(3): 993-1004, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33754566

RESUMEN

We built a comprehensive evaluation index system of urbanization in Chengdu-Chongqing (Cheng-Yu) urban agglomeration from four subsystems, including the economic, social, ecological, and urban and rural coordination. The comprehensive evaluation index system of eco-environment was constructed by combining ecological environment carrying capacity and ecological flexibi-lity. The coupling coordination degree model was applied to quantify the coupling coordination degree between urbanization and eco-environment in the prefecture-level cities of Cheng-Yu urban agglo-meration from 2005 to 2018. With GIS spatial analysis, phenomenon analysis and Tapio model, we analyzed the interaction type, evolution path and path of decoupling between urbanization and eco-environment in the prefecture-level cities of Cheng-Yu urban agglomeration. The results showed that the urbanization quality of Cheng-Yu urban agglomeration showed a trend of fluctuation and rise during the study period. Both Chengdu and Chongqing as high value areas showed "double-core" radia-ting to the surrounding areas. The eco-environment quality showed a slowly rising trend. The spatial pattern was a " U " shape with a north opening, high perimeter and low center. The degree of coupling coordination between the urbanization system and the eco-environment system was rising, with a spatial pattern of low in the middle and high in the east and west. The overall level of coupling coordination was relatively high. The type of coupling coordination degree was gradually evolving from near-disorder and reluctant coordination to moderate coordination. The evolution paths of urbanization and eco-environmental interaction were divided into two categories: stable and changing. The stable type included 20 cities in 5 subcategories, with Chengdu, Deyang, Mianyang, etc. being always well-coordination. The change type included 16 cities in 9 subcategories. The coordination degree of Chongqing main urban area, Tongliang and most other cities was improved, showing "rising" development. Hechuan, Zigong and a few other cities showed "sinking" development. The growth rates of both ecological environment and urbanization were positive. The decoupling state of urbanization and ecological environment was mainly characterized by weak decoupling and expansion connection.


Asunto(s)
Conservación de los Recursos Naturales , Urbanización , China , Ciudades , Análisis Espacial
8.
Ann Palliat Med ; 10(2): 2158-2166, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33725771

RESUMEN

BACKGROUND: The risk of injury to the kidney can be significantly exacerbated by the presence of tumors and the effects of related treatments. Kidney injury associated with cancer is common in multiple myeloma, tumor lysis syndrome, hematopoietic stem cell therapy, and chemotherapy. Cancer patients are at increased risk of infection, sepsis, tumor lysis syndrome, drug-related toxicity, and other comorbidities, leading to a significantly increased risk of acute kidney injury (AKI). This study retrospectively analyzed the clinical data of AKI in cancer patients and explored the predictive value of Cystatin C (CysC) in the prognosis of cancer patients with AKI. METHODS: Cancer patients attending the Fifth People's Hospital of Shenyang from April 2014 to March 2019 were enrolled according to inclusion and exclusion criteria. Cancer patients with AKI were divided into two groups according to the changes in renal function during the follow-up period: a renal function recovery group and a nonrecovery group. The differences in baseline data of the two groups were compared. Logistic univariate and multivariate regression analyses were conducted to determine the risk of renal function failure. RESULTS: A total of 3,127 cases were included. Among them, 659 cases (21.1%) had AKI, and 2,468 cases had no AKI. Among the 659 AKI patients, 473 (71.8%) patients' renal function recovered, while 186 (28.2%) did not. Logistic univariate and multivariate regression analyses indicated that age [odds ratio (OR) =1.133, 95% confidence interval (CI): 1.064-1.219], diabetes (OR =1.226, 95% CI: 1.093-1.385), chronic kidney disease (CKD) (OR =1.347, 95% CI: 1.108-1.624), hematological malignancies (OR =1.174, 95% CI: 1.063-1.311), chemotherapy (OR =1.119, 95% CI: 1.055-1.304), systolic blood pressure (OR =1.108, 95% CI: 1.062-1.267), serum creatinine (Scr) (OR =1.262, 95% CI: 1.105-1.446), and CysC (OR =1.416, 95% CI: 1.251-1.739) were related to the failure of renal function to recover after AKI. CONCLUSIONS: Baseline CysC level is associated with the occurrence of AKI in cancer patients and a failure to recover renal function during follow-up.

9.
Am J Hematol ; 96(5): 561-570, 2021 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-33606900

RESUMEN

Globally, postpartum hemorrhage (PPH) is the leading cause of maternal death. Women with immune thrombocytopenia (ITP) are at increased risk of developing PPH. Early identification of PPH helps to prevent adverse outcomes, but is underused because clinicians do not have a tool to predict PPH for women with ITP. We therefore conducted a nationwide multicenter retrospective study to develop and validate a prediction model of PPH in patients with ITP. We included 432 pregnant women (677 pregnancies) with primary ITP from 18 academic tertiary centers in China from January 2008 to August 2018. A total of 157 (23.2%) pregnancies experienced PPH. The derivation cohort included 450 pregnancies. For the validation cohort, we included 117 pregnancies in the temporal validation cohort and 110 pregnancies in the geographical validation cohort. We assessed 25 clinical parameters as candidate predictors and used multivariable logistic regression to develop our prediction model. The final model included seven variables and was named MONITOR (maternal complication, WHO bleeding score, antepartum platelet transfusion, placental abnormalities, platelet count, previous uterine surgery, and primiparity). We established an easy-to-use risk heatmap and risk score of PPH based on the seven risk factors. We externally validated this model using both a temporal validation cohort and a geographical validation cohort. The MONITOR model had an AUC of 0.868 (95% CI 0.828-0.909) in internal validation, 0.869 (95% CI 0.802-0.937) in the temporal validation, and 0.811 (95% CI 0.713-0.908) in the geographical validation. Calibration plots demonstrated good agreement between MONITOR-predicted probability and actual observation in both internal validation and external validation. Therefore, we developed and validated a very accurate prediction model for PPH. We hope that the model will contribute to more precise clinical care, decreased adverse outcomes, and better health care resource allocation.

10.
Biomed Res Int ; 2021: 4084371, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33553423

RESUMEN

Objective: Sepsis is a leading cause of acute lung injury (ALI). This study attempted to investigate the effects of limb bud and heart (LBH) on the development of sepsis-induced ALI and its underlying mechanism of action. Methods: The sepsis-induced ALI mouse model was established by cecal ligation and puncture (CLP). The lung injury score and lung wet/dry weight (W/D) ratio were used to evaluate the lung injury. In vitro, ALI was simulated by lipopolysaccharide (LPS) treatment in A549 cells. The mRNA expression of LBH, NLRP3, ASC, and proinflammatory cytokines was measured by qRT-PCR. The viability of LPS-induced A549 cells was analyzed by MTT assay. Furthermore, western blot was performed to detect the protein expression of LBH, NLRP3, and ASC. LPS-induced A549 cells were treated with MCC950 (NLRP3 inflammasome inhibitor) to confirm the effect of LBH on NLRP3 inflammasome. Results: The mRNA and protein expression of LBH was decreased in sepsis-induced ALI. LBH overexpression reduced the lung injury score, lung W/D ratio, expression of proinflammatory cytokines, and NLRP3 inflammasome activation in sepsis-induced ALI mouse model. Additionally, LBH upregulation increased the viability, while it decreased the proinflammatory cytokine expression and NLRP3 inflammasome activation of LPS-induced A549 cells. Moreover, MCC950 reversed the promoting effects of LBH silencing on proinflammatory cytokine expression and NLRP3 inflammasome activation in LPS-induced A549 cells. Conclusions: LBH alleviated lung injury in sepsis-induced ALI mouse model by inhibiting inflammation and NLRP3 inflammasome, and restrained the inflammation by inhibiting NLRP3 inflammasome in LPS-induced A549 cells, providing a novel therapeutic target for ALI.

11.
ACS Nano ; 2021 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-33624496

RESUMEN

The conversion of CO2 into fuels and feedstock chemicals via photothermal catalysis holds promise for efficient solar energy utilization to tackle the global energy shortage and climate change. Despite recent advances, it is of emerging interest to explore promising materials with excellent photothermal properties to boost the performance of photothermal CO2 catalysis. Here, we report the discovery of MXene materials as superior photothermal supports for metal nanoparticles. As a proof-of-concept study, we demonstrate that Nb2C and Ti3C2, two typical MXene materials, can enhance the photothermal effect and thus boost the photothermal catalytic activity of Ni nanoparticles. A record CO2 conversion rate of 8.50 mol·gNi-1·h-1 is achieved for Nb2C-nanosheet-supported Ni nanoparticles under intense illumination. Our study bridges the gap between photothermal MXene materials and photothermal CO2 catalysis toward more efficient solar-to-chemical energy conversions and stimulates the interest in MXene-supported metal nanoparticles for other heterogeneous catalytic reactions, particularly driven by sunlight.

12.
Food Funct ; 12(4): 1803-1817, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33523066

RESUMEN

BACKGROUND: The anti-inflammatory effect of n-3 PUFAs has been widely documented. Emerging evidence suggests that the main component of n-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may have differential effects in ulcerative colitis (UC). It was aimed to clarify their differential effects in UC. METHODS: Eight-week-old male C57BL/6J mice were randomly divided into 7 groups, namely control, UC model, salicylazosulfapyridine (SASP), low-dose DHA, high-dose DHA, low-dose EPA, and high-dose EPA. DHA, EPA and SASP treatment groups were orally treated accordingly for 9 weeks. During the 5th to 9th week the control group was given distilled water, while other groups were given distilled water with 2% dextran sodium sulfate (DSS) to induce UC. Body weight loss, diarrhea, and stool bleeding were recorded to calculate the disease activity index (DAI). The level of tight junction proteins Claudin-1 and Occludin, and cytokines including TNF-α, IL-6, and IL-1ß as well as inflammatory cell markers such as MPO, F4/80, and MCP-1 in the intestinal epithelium were measured using western blotting. Activation of IL-6/STAT3 and NLRP3/IL-1ß inflammatory pathways was also assessed. Levels of proliferation-related proteins of the Wnt/ß-catenin pathway with c-myc, Cyclin-D1, and PCNA were detected. RESULTS: EPA, superior to DHA, significantly attenuated DSS-induced colitis evidenced by reduced DAI scores, cytokine production and inflammatory cell infiltration. Mechanically, EPA triggered a marked up-regulation of Claudin-1 and Occludin with down-regulation of their up-stream Akt and ERK. EPA also inhibited NLRP3/IL-1ß and IL-6/STAT3 inflammatory pathways and up-regulated the Wnt/ß-catenin pathway. CONCLUSIONS: EPA is more suitable to be used for the treatment of UC than DHA.

13.
Artículo en Inglés | MEDLINE | ID: mdl-33590751

RESUMEN

In this work, we present a simple and efficient solution-doping process for preparing high-quality polycrystalline silicon (poly-Si)-based passivating contacts. Commercial phosphorus or boron-doping solutions are spin-coated on crystalline silicon (c-Si) wafers that feature SiO2/poly-Si layers; the doping process is then activated by thermal annealing at high temperatures in a nitrogen atmosphere. With optimized n- and p-type solution doping and thermal annealing, n- and p-type poly-Si passivating contacts featuring simultaneously a low contact recombination parameter (J0c) of 2.4 and 12 fA/cm2 and a low contact resistivity (ρc) of 29 and 20 mΩ·cm2 are achieved, respectively. Taking advantage of the single-sided nature of these solution-doping processes, c-Si solar cells with poly-Si passivating contacts of opposite polarity on the respective wafer surfaces are fabricated using a simple coannealing process, achieving the best power conversion efficiency (PCE) of 18.5% on a planar substrate. Overall, the solution-doping method is demonstrated to be a simple and promising alternative to gas/ion implantation doping for poly-Si passivating-contact manufacturing.

14.
J Magn Reson Imaging ; 2021 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-33559360

RESUMEN

BACKGROUND: Aberrant static functional connectivity (FC) has been well demonstrated in amyotrophic lateral sclerosis (ALS); however, ALS-related alterations in FC dynamic properties remain unclear, although dynamic FC analyses contribute to uncover mechanisms underlying neurodegenerative disorders. PURPOSE: To explore dynamic functional network connectivity (dFNC) in ALS and its correlation with disease severity. STUDY TYPE: Prospective. SUBJECTS: Thirty-two ALS patients and 45 healthy controls. FIELD STRENGTH/SEQUENCE: Multiband resting-state functional images using gradient echo echo-planar imaging and T1-weighted images were acquired at 3.0 T. ASSESSMENT: Disease severity was evaluated with the revised ALS Functional Rating Scale (ALSFRS-R) and patients were stratified according to diagnostic category. Independent component analysis was conducted to identify the components of seven intrinsic brain networks (ie, visual/sensorimotor (SMN)/auditory/cognitive-control (CCN)/default-mode (DMN)/subcortical/cerebellar networks). A sliding-window correlation approach was used to compute dFNC. FNC states were determined by k-mean clustering, and state-specific FNC and dynamic indices (fraction time/mean dwell time/transition number) were calculated. STATISTICAL TESTS: Two-sample t test used for comparisons on dynamic measures and Spearman's correlation analysis. RESULTS: ALS patients showed increased FNC between DMN-SMN in state 1 and between CCN-SMN in state 4. Patients remained in state 2 (showing the weakest FNC) for a significantly longer time (mean dwell time: 49.8 ± 40.1 vs. 93.6 ± 126.3; P < 0.05) and remained in state 1 (showing a relatively strong FNC) for a shorter time (fraction time: 0.27 ± 0.25 vs. 0.13 ± 0.20; P < 0.05). ALS patients exhibited less temporal variability in their FNC (transition number: 10.2 ± 4.4 vs. 7.8 ± 3.8; P < 0.05). A significant correlation was observed between ALSFRS-R and mean dwell time in state 2 (r = -0.414, P < 0.05) and transition number (r = 0.452, P < 0.05). No significant between-subgroup difference in dFNC properties was found (all P > 0.05). DATA CONCLUSION: Our findings suggest aberrant dFNC properties in ALS, which is associated with disease severity. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

15.
Nat Commun ; 12(1): 20, 2021 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-33397932

RESUMEN

Drug resistance and tumor recurrence are major challenges in cancer treatment. Cancer cells often display centrosome amplification. To maintain survival, cancer cells achieve bipolar division by clustering supernumerary centrosomes. Targeting centrosome clustering is therefore considered a promising therapeutic strategy. However, the regulatory mechanisms of centrosome clustering remain unclear. Here we report that KIFC1, a centrosome clustering regulator, is positively associated with tumor recurrence. Under DNA damaging treatments, the ATM and ATR kinases phosphorylate KIFC1 at Ser26 to selectively maintain the survival of cancer cells with amplified centrosomes via centrosome clustering, leading to drug resistance and tumor recurrence. Inhibition of KIFC1 phosphorylation represses centrosome clustering and tumor recurrence. This study identified KIFC1 as a prognostic tumor recurrence marker, and revealed that tumors can acquire therapeutic resistance and recurrence via triggering centrosome clustering under DNA damage stresses, suggesting that blocking KIFC1 phosphorylation may open a new vista for cancer therapy.


Asunto(s)
Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Centrosoma/metabolismo , Cinesina/metabolismo , Recurrencia Local de Neoplasia/metabolismo , Secuencia de Aminoácidos , Animales , Línea Celular Tumoral , Inestabilidad Cromosómica , Daño del ADN , Resistencia a Antineoplásicos , Humanos , Cinesina/química , Ratones , Recurrencia Local de Neoplasia/patología , Fosforilación , Fosfoserina/metabolismo
16.
BMC Pregnancy Childbirth ; 21(1): 40, 2021 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-33422023

RESUMEN

BACKGROUND: Maternal admission to the intensive care unit (ICU) during pregnancy or in the postpartum period is a marker of severe acute maternal morbidity. Mechanical ventilation is an important and basic method of maintaining life support in the ICU, but prolonged mechanical ventilation (PMV) is associated with a prolonged length of hospital stay and other adverse outcomes. Therefore, we conducted this retrospective study to describe morbidity and further try to identify the risk factors for PMV in critically ill obstetric women. METHODS: The clinical data were obtained from a single-centre retrospective comparative study of 143 critically ill obstetric patients at a tertiary teaching hospital in mainland China between January 1, 2009, and December 31, 2019. PMV was defined as a mechanical ventilation length of more than 24 h. Clinical and obstetric parameters were collected to analyse the risk factors for PMV. Patients were separated into groups with and without PMV. Potential risk factors were identified by univariate testing. Multivariate logistic regression was used to evaluate independent predictors of PMV. RESULTS: Out of 29,236 hospital deliveries, 265 critically ill obstetric patients entered the ICU. One hundred forty-five (54.7%) of them were treated with mechanical ventilation. Two were excluded because of death within 24 h. Sixty-five critically ill obstetric patients (45.5%) underwent PMV. The independent risk factors for PMV included estimated blood loss (odds ratio (OR) =1.296, P=0.029), acute kidney injury (AKI) (OR=4.305, P=0.013), myocardial injury (OR=4.586, P=0.012), and PaO2/FiO2 (OR=0.989, P< 0.001). The area under the receiver operating characteristic (ROC) curve based on the predicted probability of the logistic regression was 0.934. CONCLUSIONS: Estimated blood loss, AKI, myocardial injury, and PaO2/FiO2 were independent risk factors for PMV in critically ill obstetric patients.

17.
Int J Radiat Biol ; 97(4): 464-473, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33464146

RESUMEN

PURPOSE: Baicalein (an anti-ferroptosis drug) was recently reported to synergistically improve the survival rate of mice following a high dose of total body irradiation with anti-apoptosis and anti-necroptosis drugs. At the same time, our group has demonstrated that ferrostatin-1, a ferroptosis inhibitor, improves the survival rate of a mouse model of hematopoietic acute radiation syndrome to 60% for 150 days (p < .001). These phenomena suggest that ferroptosis inhibition can mitigate radiation damage. In this study, we continued to study the mechanisms by which ferrostatin-1 alleviated radiation-induced ferroptosis and subsequent hematopoietic acute radiation syndrome. MATERIALS AND METHODS: Male ICR mice (8-10 weeks old) were exposed to doses of 0, 8, or 10 Gy irradiated from a 137Cs source. Ferrostatin-1 was intraperitoneally injected into mice 72 h post-irradiation. Bone marrow mononuclear cells (BMMCs) and peripheral blood cells were counted. The changes in iron-related parameters, lipid metabolic enzymes, lipid peroxidation repair molecules (glutathione peroxidase 4, glutathione, and coenzyme Q10), and inflammatory factors (TNF-α, IL-6, and IL-1ß) were evaluated using biochemical or antibody techniques. RESULTS: Ferrostatin-1 increased the number of red and white blood cells, lymphocytes, and monocytes in the peripheral blood after total body irradiation in mice by mitigating the ferroptosis of BMMCs. Total body irradiation induced ferroptosis in BMMCs by increasing the iron and lipid peroxidation levels and depleting the acyl-CoA synthetase long-chain family member 4 (ASCL4), lipoxygenase 15, glutathione peroxidase 4, and glutathione levels. Ferroptotic BMMCs did not release TNF-α, IL-6, or IL-1ß at the early stage of radiation exposure. Ferrostatin-1 mitigated the lipid peroxidation of radiation-induced ferroptosis by attenuating increases in levels of hemosiderin and liable iron pool and decreases in levels of ASCL4 and glutathione peroxidase 4. CONCLUSIONS: The onset of total body irradiation-induced ferroptosis in BMMCs involved changes in iron, lipid metabolic enzymes, and anti-lipid peroxidation molecules. Ferrostatin-1 could be a potential radiation mitigation agent by acting on these targets.

18.
Neurochem Res ; 46(3): 523-534, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33394222

RESUMEN

Voltage-gated sodium channels (VGSCs) are fundamental to the initiation and propagation of action potentials in excitable cells. Ca2+/calmodulin (CaM) binds to VGSC type II (NaV1.2) isoleucine and glutamine (IQ) motif. An autism-associated mutation in NaV1.2 IQ motif, Arg1902Cys (R1902C), has been reported to affect the combination between CaM and the IQ motif compared to that of the wild type IQ motif. However, the detailed properties for the Ca2+-regulated binding of CaM to NaV1.2 IQ (1901Lys-1927Lys, IQwt) and mutant IQ motif (IQR1902C) remains unclear. Here, the binding ability of CaM and CaM's constituent proteins including N- and C lobe to the IQ motif of NaV1.2 and its mutant was investigated by protein pull-down experiments. We discovered that the combination between CaM and the IQ motif was U-shaped with the highest at [Ca2+] ≈ free and the lowest at 100 nM [Ca2+]. In the IQR1902C mutant, Ca2+-dependence of CaM binding was nearly lost. Consequently, the binding of CaM to IQR1902C at 100 and 500 nM [Ca2+] was increased compared to that of IQwt. Both N- and C lobe of CaM could bind with NaV1.2 IQ motif and IQR1902C mutant, with the major effect of C lobe. Furthermore, CaMKII had no impact on the binding between CaM and NaV1.2 IQ motif. This research offers novel insight to the regulation of NaV1.2 IQwt and IQR1902C motif, an autism-associated mutation, by CaM.

19.
Transl Oncol ; 14(4): 101023, 2021 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-33486313

RESUMEN

BACKGROUND: Carnitine palmitoyltransferase 2 (CPT2) is a rate-limiting enzyme involved in fatty acid ß-oxidation (FAO) regulation. Recently, it has been increasingly recognized that lipid metabolism dysregulation is closely implicated in tumorigenesis. However, the involvement of CPT2 in the progression of cancer is still largely unclear, especially in ovarian cancer (OC). METHODS: In the present study, CPT2 expression and its clinical significance were determined in OC tissues and cells. The biological functions and molecular mechanisms of CPT2 in OC growth and metastasis were determined by in vitro and in vivo assays. FINDINGS: We found that CPT2 was frequently down-regulated in primary ovarian serous carcinomas, which is significantly correlated with poor survival of ovarian cancer patients. Functional experiments revealed that CPT2 inhibited OC cell growth and metastasis via suppression of G1/S cell cycle transition and epithelial to mesenchymal transition (EMT), as well as induction of cell apoptosis. Mechanistically, suppression of ROS/NFκB signaling pathway by increasing fatty acid oxidation-derived NADPH production was involved in the anti-tumorigenic functions of CPT2 in OC cells. INTERPRETATION: Altogether, our findings demonstrate that CPT2 functions as a potential tumor suppressor in OC progression. CPT2 may serve as a novel prognostic marker and therapeutic target in OC.

20.
Environ Pollut ; 271: 116373, 2021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-33418288

RESUMEN

The odor problems in river-type micro-polluted water matrixes are complicated compared to those in lakes and reservoirs. For example, the TY River in Jiangsu Province has been associated with complex odors, whereas the specific odor compounds were not clear. In this paper, a comprehensive study on characterizing the odors and odorants in source water from the TY River was conducted. Six odor types, including earthy, marshy, fishy, woody, medicinal, and chemical odors, were detected for the first time; correspondingly, thirty-three odor-causing compounds were identified. By means of evaluating odor activity values and reconstituting the identified odorants, 95, 93, 92, 90, 89 and 88% of the earthy, marshy, fishy, woody, medicinal and chemical odors in the source waters could be clarified. Geosmin and 2-methylisoborneol were associated with earthy odor, while amyl sulfide, dibutyl sulfide, propyl sulfide, dimethyl disulfide, dimethyl trisulfide and indole were related to marshy odor. The major woody and fishy odor compounds were vanillin, geraniol, ß-cyclocitral and 2,4-decadienal, 2-octenal, respectively. Medicinal and chemical odors were mainly caused by 2-chlorophenol, 4-bromophenol, 2,6-dichlorophenol and naphthalene, and 1,4-dichlorobenzene, respectively. This is the first study in which six odor types and thirty-three odorants were identified simultaneously in a river-type micro-polluted water source, which can offer a reference for odor management in drinking water treatment plants.


Asunto(s)
Odorantes , Purificación del Agua , Animales , Ríos , Agua , Contaminación del Agua
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