Publications by authors named "Jun Lu"

2,454 Publications

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Discovery of novel N-1 substituted pyrazolopyrimidinones as potent, selective PDE2 inhibitors.

Bioorg Med Chem Lett 2021 May 12:128082. Epub 2021 May 12.

Discovery Chemistry, Merck & Co., Inc., 213 E. Grand Avenue, South San Fransisco, CA, 94080 USA.

A focused SAR study was conducted on a series of N1-substituted pyrazolopyrimidinone PDE2 inhibitors to reveal compounds with excellent potency and selectivity. The series was derived from previously identified internal leads and designed to enhance steric interactions with key amino acids in the PDE2 binding pocket. Compound 26 was identified as a lead compound with excellent PDE2 selectivity and good physicochemical properties.
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http://dx.doi.org/10.1016/j.bmcl.2021.128082DOI Listing
May 2021

Osimertinib alone as second-line treatment for brain metastases (BM) control may be more limited than for non-BM in advanced NSCLC patients with an acquired EGFR T790M mutation.

Respir Res 2021 May 11;22(1):145. Epub 2021 May 11.

Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, No.241 Huaihai West Road, Xuhui District, Shanghai, 200030, China.

Background: This study was designed to investigate the difference between brain metastases (BM) and non-brain metastases (non-BM) treated by osimertinib in advanced patients with an acquired EGFR T790M mutation after obtaining first-generation EGFR-TKI resistance.

Methods: A total number of 135 first-generation EGFR-TKI-resistant patients with an acquired EGFR T790M mutation were retrospectively analyzed. The patients were divided into BM and non-BM groups. According to the type of treatment (whether brain radiotherapy), the BM patients were divided into an osimertinib combined with brain radiotherapy group and an osimertinib without brain radiotherapy group. In addition, according to the type of BM (the sequence between BM and osimertinib), the BM patients were subdivided into an osimertinib after BM group (initial BM developed after obtaining first-generation EGFR-TKI resistance) and an osimertinib before BM group (first-generation EGFR-TKI resistance then osimertinib administration performed; initial BM was not developed until osimertinib resistance). The progression-free survival (PFS) and overall survival (OS) were evaluated. The primary endpoint was OS between BM and no-BM patients. The secondary endpoints were PFS of osimertinib, and OS between brain radiotherapy and non-brain radiotherapy patients.

Results: A total of 135 patients were eligible and the median follow-up time of all patients was 50 months. The patients with BM (n = 54) had inferior OS than those without BM (n = 81) (45 months vs. 55 months, P = 0.004). And in BM group, the OS was longer in patients that received osimertinib combined with brain radiotherapy than in those without brain radiotherapy (53 months vs. 40 months, P = 0.014). In addition, the PFS was analysed according to whether developed BM after osimertinib resistance. The PFS of the patients that developed BM after acquiring osimertinib resistance was shorter than that without BM development, whether patients developed initial BM after first-generation EGFR-TKI resistance (7 months vs. 13 months, P = 0.003), or developed non-BM after first-generation EGFR-TKI resistance (13 months vs. 17 months, P < 0.001).

Conclusions: In advanced patients with an acquired EGFR T790M mutation after obtaining first-generation EGFR-TKI resistance, osimertinib may be more limited in its control in BM than in non-BM. Also, osimertinib combined with brain radiotherapy may improve the survival time of BM patients.
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http://dx.doi.org/10.1186/s12931-021-01741-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114713PMC
May 2021

Nanotechnology for Sulfur Cathodes.

ACS Nano 2021 May 7. Epub 2021 May 7.

Chemical Sciences and Engineering Division, Argonne National Laboratory, 9700 Cass Avenue, Lemont, Illinois 60439, United States.

The field of lithium-sulfur batteries has benefited enormously from the advances in nanotechnology. At each step of technological improvement, lithium-sulfur batteries have relied upon techniques and methodologies brought upon by nanotechnology. Nanoporous material, heterogeneous nanocomposite, and hierarchical electrode developments have all been well-established as critical milestones for lithium-sulfur batteries. This review will briefly discuss the specific major roles of nanotechnology in lithium-sulfur batteries regarding practically relevant testing conditions in addition to research trends and future directions for electrocatalysis.
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http://dx.doi.org/10.1021/acsnano.1c01999DOI Listing
May 2021

The protective role of serum uric acid against premature membrane rupture in gestational diabetes: a cross-sectional study.

BMC Endocr Disord 2021 May 6;21(1):95. Epub 2021 May 6.

Department of Endocrinology and Metabolism, Institute/University/Hospital: Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, No. 105 Jiefang Road, Jinan City, 250013, Shandong Province, China.

Background: Uric acid has strong antioxidant activity, whereas its oxidative damage is closely related to many diseases. We assessed the association between serum uric acid (SUA) levels and premature rupture of membranes (PROM) in pregnant women with gestational diabetes (GDM) in China.

Methods: In this cross-sectional study, a total of 456 pregnant women were enrolled. Anthropometric parameters for pregnant women were collected within 12 weeks of gestation. Weight gain during pregnancy was obtained from the patients' records. GDM was diagnosed according to 75-g oral glucose tolerance tests at the 24-28th week of gestation, and SUA was determined simultaneously. PROM was identified as the natural rupture of foetal membranes before the first stage of labour. Logistic models were fitted to identify the presence of PROM using clinical characteristics with (Model 2) or without serum uric acid (Model 1).

Results: There were differences in BMI, haemoglobin A1c, fasting blood glucose, 1-h postprandial glucose (PG), 2-h PG, insulin levels, triglycerides,weight gain during pregnancy, the rate of macrosomia, fetus birth weight and PROM between women with and without GDM (all P < 0.05). Furthermore, GDM women with PROM had lower levels of SUA compared to those without PROM (P = 0.030). The odds ratio of PROM decreased with increasing SUA levels. The area under the receiver operating characteristic curves for PROM based on Model 2 was larger than that in Model 1 (0.86 versus 0.71, P < 0.05).

Conclusion: Relatively elevated SUA levels at the 24-28th weeks of gestation were associated with a lower risk of PROM in women with GDM. Therefore, SUA may be a protective factor for PROM in GDM patients. The optimal concentration of uric acid in different diseases and different populations needs to be further studied.
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http://dx.doi.org/10.1186/s12902-021-00736-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101033PMC
May 2021

Percutaneous gastrostomy compared with esophageal stenting for the treatment of esophageal cancer with dysphagia.

J Vasc Interv Radiol 2021 May 3. Epub 2021 May 3.

Minimally Invasive and Interventional Department, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, Henan, China. Electronic address:

Purpose: To compare the outcomes of self-expandable metal stent and percutaneous gastrostomy (PG) for treatment of patients with esophageal cancer (EC) and dysphagia.

Materials And Methods: This retrospective observational study consisted of 113 patients with EC and dysphagia who underwent either stent insertion (n = 47) or PG (n = 66) at a single center between June 2014 and June 2018.

Results: There were 63 men and 50 women with the mean age of 76.5 ± 4.9 years. The two groups had similar baseline characteristics, except that the PG group had a higher percentage of patients with cervical EC (22.7%. vs 2.1%, P < 0.001). The PG group had better maintenance of nutritional status in terms of reduction of serum albumin level (P = 0.039) and weight loss (P = 0.041). Compared with the stent group, the PG group demonstrated a lower incidence of local severe pain (0% vs 21.3%, P < 0.001), and lower incidence of dislodgment of device (1.5% vs 19.1%, P = 0.002). The PG group demonstrated longer overall survival than the stent group, for stages II and III (201 vs 185 days, P = 0.034) and stage IV (122 vs 86 days, P = 0.001).

Conclusion: Compared with stent insertion, PG is associated with better maintenance of nutritional status, fewer complications, and better survival. Thus, PG may be the preferred choice for treating malnutrition in patients with EC and dysphagia.
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http://dx.doi.org/10.1016/j.jvir.2021.04.019DOI Listing
May 2021

Additive Effect of Coexisting Aneurysms Increases Subarachnoid Hemorrhage Risk in Patients With Multiple Aneurysms.

Stroke 2021 May 6:STROKEAHA120032500. Epub 2021 May 6.

Department of Neurosurgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China (X.F., P.Q., J.L., D.W.).

Background And Purpose: It remains unclear whether the additive effect of coexisting intracranial aneurysms increases the risk of subarachnoid hemorrhage (SAH) in patients with multiple intracranial aneurysms. We have performed a tentative analysis for the additive effect of coexisting aneurysms.

Methods: This multi-institutional cross-sectional study included 1781 aneurysms from 746 patients with multiple intracranial aneurysms. Using the generalized linear mixed model, we analyzed risk factors associated with individual aneurysm rupture and assessed the additive risk of SAH for each patient.

Results: The coexisting aneurysms number was not significantly associated with individual intracranial aneurysm rupture, both in unadjusted and adjusted analyses. Patient-level analysis found that an increased number of coexisting aneurysms was significantly associated with a greater estimated additive risk (<0.001). Estimated additive risks of patients with 2, 3, and 4 or more coexisting intracranial aneurysms were 25.9%, 31.8%, and 38.1%, respectively, which are comparable to the actual incidence of SAH in those patients (26.6%, 29.5%, and 36.5%, respectively), with a Spearman correlation coefficient of 1.000 (<0.001). Compared with aneurysm-related factors, the estimated additive effect had better discrimination power for SAH risk, with areas under the receiver operating characteristic curve of 0.821.

Conclusions: We found that a greater number of coexisting aneurysms did not increase rupture risk of individual aneurysms, but the potential additive effect might increase SAH risk in patients with multiple intracranial aneurysms.
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http://dx.doi.org/10.1161/STROKEAHA.120.032500DOI Listing
May 2021

Arginine and lysine methylation of MRPS23 promotes breast cancer metastasis through regulating OXPHOS.

Oncogene 2021 Apr 29. Epub 2021 Apr 29.

The Key Laboratory of Molecular Epigenetics of Ministry of Education (MOE), Northeast Normal University, Changchun, China.

Mitochondrial oxidative phosphorylation (OXPHOS) is a vital regulator of tumor metastasis. However, the mechanisms governing OXPHOS to facilitate tumor metastasis remain unclear. In this study, we discovered that arginine 21(R21) and lysine 108 (K108) of mitochondrial ribosomal protein S23 (MRPS23) was methylated by the protein arginine methyltransferase 7 (PRMT7) and SET-domain-containing protein 6 (SETD6), respectively. R21 methylation accelerated the poly-ubiquitin-dependent degradation of MRPS23 to a low level. The MRPS23 degradation inhibited OXPHOS with elevated mtROS level, which consequently increased breast cancer cell invasion and metastasis. In contrast, K108 methylation increased MRPS23 stability, and K108 methylation coordinated with R21 methylation to maintain a low level of MRPS23, which was in favor of supporting breast cancer cell survival through regulating OXPHOS. Consistently, R21 and K108 methylation was correlated with malignant breast carcinoma. Significantly, our findings unveil a unique mechanism of controlling OXPHOS by arginine and lysine methylation and point to the impact of the PRMT7-SETD6-MRPS23 axis during breast cancer metastasis.
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http://dx.doi.org/10.1038/s41388-021-01785-7DOI Listing
April 2021

A Study on Hematopoietic Stem Cell Donation Volunteer Retention between Swab Sampling Approach and Blood Sampling Approach: Evidence from Shanghai, China.

Int J Environ Res Public Health 2021 Apr 12;18(8). Epub 2021 Apr 12.

Department of Health Policy and Management, School of Public Health, Fudan University, Shanghai 200032, China.

The loss of hematopoietic stem cell donation (HSCD) volunteers is widespread worldwide. This study analyzed the distribution characteristics of volunteer retention between the swab sampling approach and blood sampling approach. The Shanghai branch of the China Bone Marrow Donation Program conducted a telephone follow-up with 18,963 volunteers to understand volunteer retention. Multiple logistic regression was used to analyze the distribution characteristics of volunteer retention between two different sampling approaches, and a forest plot was used to observe the distribution trend. Only 32.37% of the volunteers could be contacted, and the loss of volunteers was severe. The volunteer retention is influenced by sampling approaches and demographic characteristics, and Shanghai natives, the highly educated, and students had better retention. The volunteer retention of the swab group was better among young people and technicians, while the volunteer retention of the blood sample group was lower among public officials and workers, and the volunteer retention in the blood sample group was more significantly affected by changes in population characteristics. To enhance the stability of volunteers, managers should improve the contact channels and frequency, expand the ratio of stable volunteers, strengthen volunteer education in the process of collecting blood samples, and respect individuals' willingness.
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http://dx.doi.org/10.3390/ijerph18084027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069943PMC
April 2021

CCRRSleepNet: A Hybrid Relational Inductive Biases Network for Automatic Sleep Stage Classification on Raw Single-Channel EEG.

Brain Sci 2021 Apr 2;11(4). Epub 2021 Apr 2.

College of Computer Science and Technology, Heilongjiang University, Harbin 150080, China.

In the inference process of existing deep learning models, it is usually necessary to process the input data level-wise, and impose a corresponding relational inductive bias on each level. This kind of relational inductive bias determines the theoretical performance upper limit of the deep learning method. In the field of sleep stage classification, only a single relational inductive bias is adopted at the same level in the mainstream methods based on deep learning. This will make the feature extraction method of deep learning incomplete and limit the performance of the method. In view of the above problems, a novel deep learning model based on hybrid relational inductive biases is proposed in this paper. It is called CCRRSleepNet. The model divides the single channel Electroencephalogram (EEG) data into three levels: frame, epoch, and sequence. It applies hybrid relational inductive biases from many aspects based on three levels. Meanwhile, multiscale atrous convolution block (MSACB) is adopted in CCRRSleepNet to learn the features of different attributes. However, in practice, the actual performance of the deep learning model depends on the nonrelational inductive biases, so a variety of matching nonrelational inductive biases are adopted in this paper to optimize CCRRSleepNet. The CCRRSleepNet is tested on the Fpz-Cz and Pz-Oz channel data of the Sleep-EDF dataset. The experimental results show that the method proposed in this paper is superior to many existing methods.
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http://dx.doi.org/10.3390/brainsci11040456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065855PMC
April 2021

Genistein improves systemic metabolism and enhances cold resistance by promoting adipose tissue beiging.

Biochem Biophys Res Commun 2021 Jun 26;558:154-160. Epub 2021 Apr 26.

Department of Pediatrics, The Second Xiangya Hospital, Central South University, Changsha, 410010, China. Electronic address:

Genistein, a naturally occurring phytoestrogen and a member of the large class of compounds known as isoflavones, exerts protective effects in several diseases. Recent studies indicate that genistein plays a critical role in controlling body weight, obesity-associated insulin resistance, and metabolic disorders, but its target organs in reversing obesity and related pathological conditions remain unclear. In this study, we showed that mice supplemented with 0.2% genistein in a high-fat diet for 12 weeks showed enhanced metabolic homeostasis, including reduced obesity, improved glucose uptake and insulin sensitivity, and alleviated hepatic steatosis. We also observed a beiging phenomenon in the white adipose tissue and reversal of brown adipose tissue whitening in these mice. These changes led to enhanced resistance to cold stress. Altogether, our data suggest that the improved metabolic profile in mice treated with genistein is likely a result of enhanced adipose tissue function.
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http://dx.doi.org/10.1016/j.bbrc.2021.04.067DOI Listing
June 2021

Prognostic importance of dynamic changes in systemic inflammatory markers for patients with gastric cancer.

J Surg Oncol 2021 Apr 29. Epub 2021 Apr 29.

Departmennt of Gastric Surgery, Union Hospital, Fujian Medical University, Fuzhou, Fujian, China.

Purpose: To investigate the effect of dynamic changes in systemic inflammatory markers (SIM) on long-term prognosis of patients with gastric cancer (GC).

Methods: A retrospective analysis was performed on the data of 2180 patients with GC who underwent radical gastrectomy in the Fujian medical university Union Hospital from January 2009 to December 2014. Changes in SIM between preoperatively and 1-6 months and 12 months postoperatively were reported.

Results: In multivariate analysis, higher preoperative systemic inflammation score (pre-SIS) was independent predictor of poor prognosis (p < 0.05). The optimal time of remeasurement was 12 months postoperatively, based on a longitudinal profile of SIS and accuracy in predicting 5-year overall survival (OS) (area under the curve: 0.712 [95% confidence interval: 0.630-0.785]). According to the association between the conversion of SIS and OS, we classified patients into three risk groups. Kaplan-Meier curves showed significant differences in OS among risk groups. Further Cox multivariate regression analysis showed that only risk groups of SIS and pTNM stage were independent prognostic factors for OS.

Conclusion: The efficacy of SIS in predicting prognosis 12 months after surgery is superior, and the elevation of SIS 12 months after surgery predicts poor prognosis.
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http://dx.doi.org/10.1002/jso.26498DOI Listing
April 2021

Process Engineering to Increase the Layered Phase Concentration in the Immediate Products of Flame Spray Pyrolysis.

ACS Appl Mater Interfaces 2021 Apr 28. Epub 2021 Apr 28.

Chemical Sciences and Engineering Division, Argonne National Laboratory, Lemont, Illinois 60439, United States.

Flame-spray-pyrolysis (FSP) is a robust and scalable process to synthesize particles at the commodity-scale. FSP has been used to produce the precursor powders which were converted to the layered structure (3̅ phase) by a postannealing step in making nickel-rich cathode materials (NCMs). Theoretically, the high flame temperature (normally >1500 K) in FSP can provide adequate energy for the phase conversion from rock-salt to layered structures and potentially enables one-step synthesis. However, the high flame temperature is a critical issue to cause lithium loss and structural degradation, preventing the formation of the layered phase. In this work, guided by the gaseous nucleation theory, we implemented several FSP processes with different solution recipes. The layered phase concentration in the as-burned products can be increased with the solution enthalpies. By adding a rapid quench step to suppress the lithium loss and phase degradation, the layered phase can be further increased. This work contributes new ideas to innovating process regarding the process efficiency and throughput of manufacturing cathode materials at a large scale.
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http://dx.doi.org/10.1021/acsami.1c03930DOI Listing
April 2021

Morphological Irregularity of Unruptured Intracranial Aneurysms is More Related with Aneurysm Size Rather Than Cerebrovascular Atherosclerosis: A Case-Control Study.

Clin Interv Aging 2021 20;16:665-674. Epub 2021 Apr 20.

Department of Neurosurgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China; Graduate School of Peking Union Medical College, Beijing, People's Republic of China.

Objective: It remains unclear whether irregular morphological features of intracranial aneurysms (IAs) are associated with atherosclerosis. We investigated the effect of cerebrovascular atherosclerosis stenosis (CAS) on irregular morphology of IAs.

Patients And Methods: This single-center case-control study included consecutive patients with IAs at our institution from September 2011 to September 2018. Cases were patients with irregular IAs, and age- and location-matched controls were patients with regular IAs. Conditional logistic regression models were used to assess the relationship between angiographic variables of CAS and aneurysmal irregularity.

Results: A total of 140 cases of irregular IAs and 140 controls were included in the analysis. Sixteen patients with irregular IAs (11.4%) and eleven patients with regular IAs (7.9%) had >50% parent artery stenosis; however, the differences were not statistically significant between these two groups. In addition, no significant between-group differences were observed in distributions of the cerebrovascular stenosis, number of arterial stenoses, and location of the stenosis. In the final adjusted conditional logistic regression model, only aneurysm size (≥7 mm) was significantly associated with irregular IA morphology ( = 0.022). Moreover, 89 cases of irregular IAs and 89 controls were included in the analysis of unruptured IAs (UIAs). In the final adjusted conditional logistic regression model, only aneurysm size (≥7 mm) was significantly associated with irregular UIA morphology ( = 0.020).

Conclusion: Our findings indicate that the morphological irregularity of unruptured intracranial aneurysms is more related with aneurysm size rather than cerebrovascular atherosclerosis. Further studies are needed to use prospective data to identify causative factors responsible for aneurysmal irregularity.
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http://dx.doi.org/10.2147/CIA.S301326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069126PMC
April 2021

Update on genomic and molecular landscapes of well-differentiated liposarcoma and dedifferentiated liposarcoma.

Mol Biol Rep 2021 Apr 24. Epub 2021 Apr 24.

Anatomical Pathology, PathWest, QEII Medical Centre, Perth, WA, 6009, Australia.

Well-differentiated liposarcoma (WDLPS) is the most frequent subtype of liposarcoma and may transform into dedifferentiated liposarcoma (DDLPS) which is a more aggressive subtype. Retroperitoneal lesions of WDLPS/DDLPS tend to recur repeatedly due to incomplete resections, and adjuvant chemotherapy and radiotherapy have little effect on patient survival. Consequently, identifying therapeutic targets and developing targeted drugs is critical for improving the outcome of WDLPS/DDLPS patients. In this review, we summarised the mutational landscape of WDLPS/DDLPS from recent studies focusing on potential oncogenic drivers and the development of molecular targeted drugs for DDLPS. Due to the limited number of studies on the molecular networks driving WDLPS to DDLPS development, we looked at other dedifferentiation-related tumours to identify potential parallel mechanisms that could be involved in the dedifferentiation process generating DDLPS.
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http://dx.doi.org/10.1007/s11033-021-06362-5DOI Listing
April 2021

Catalytic activity comparison of natural ferrous minerals in photo-Fenton oxidation for tertiary treatment of dyeing wastewater.

Environ Sci Pollut Res Int 2021 Apr 23. Epub 2021 Apr 23.

School of Environment Science and Engineering, Donghua University, Shanghai, 201620, People's Republic of China.

Natural ferrous minerals are readily available and recyclable catalysts in photo-Fenton-like oxidation for wastewater treatment. In this work, typical ferrous oxide and sulfide minerals including magnetite, chalcopyrite, and pyrrhotite were exploited as catalysts in heterogeneous photo-Fenton oxidation for purification of biological effluent of dyeing wastewater. In a wide initial pH range (3.0~7.5), ferrous mineral-based heterogeneous photo-Fenton-like reactions were proven to be effective on the oxidation of recalcitrant pollutants. COD removals achieved 60.57%, 58.83%, and 57.41% using pyrrhotite, chalcopyrite, and magnetite, respectively, as catalyst under ultraviolet irradiation of 220~275 nm at HO concentration of 9.8 mM. The corresponding COD removals were 51.75% and 34.09% with or without ferrous sulfate additions in UV/HO systems. Minerals exhibited excellent stability and reusability with photo-catalytic activity reduction of less than 10% in the reuse of 5 cycles. Dissolved iron concentrations were determined to be 1.86 mg L, 4.62 mg L, and 7.53 mg L for magnetite, chalcopyrite, and pyrrhotite, respectively, at pH 3 and decreased to zero in neutral pH environment, which were much lower than those required for homogenous Fenton reaction. It was deduced that oxidation of recalcitrant pollutants was mainly catalyzed by Fe(II) on the mineral surface. The more reactive oxygen species such as hydroxyl radicals were resulted from the reaction of surface Fe (II) with HO, HO photolysis, and charge separation of minerals under UV irradiation.
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http://dx.doi.org/10.1007/s11356-021-14042-xDOI Listing
April 2021

Structure and function analysis of a potent human neutralizing antibody CA521 against SARS-CoV-2.

Commun Biol 2021 04 23;4(1):500. Epub 2021 Apr 23.

Antibody Research and Development Center, Shandong Boan Biotechnology Co., Ltd., Yantai, China.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing COVID-19 pandemic, which has resulted in more than two million deaths at 2021 February . There is currently no approved therapeutics for treating COVID-19. The SARS-CoV-2 Spike protein is considered a key therapeutic target by many researchers. Here we describe the identification of several monoclonal antibodies that target SARS-CoV-2 Spike protein. One human antibody, CA521, demonstrated neutralization potential by immunizing human antibody transgenic mice. CA521 showed potent SARS-CoV-2-specific neutralization activity against SARS-CoV-2 pseudovirus and authentic SARS-CoV-2 infection in vitro. CA521 also demonstrated having a long half-life of 9.5 days in mice and 9.3 days in rhesus monkeys. CA521 inhibited SARS-CoV-2 infection in SARS-CoV-2 susceptible mice at a therapeutic setting with virus titer of the lung reduced by 4.5 logs. Structural analysis by cryo-EM revealed that CA521 recognizes an epitope overlapping with angiotensin converting enzyme 2 (ACE2)-binding sites in SARS-CoV-2 RBD in the Spike protein. CA521 blocks the interaction by binding all three RBDs of one SARS-CoV-2 spike trimer simultaneously. These results demonstrate the importance for antibody-based therapeutic interventions against COVID-19 and identifies CA521 a promising antibody that reacts with SARS-CoV-2 Spike protein to strongly neutralize its activity.
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http://dx.doi.org/10.1038/s42003-021-02029-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065039PMC
April 2021

BRD4 PROTAC degrader ARV-825 inhibits T-cell acute lymphoblastic leukemia by targeting 'Undruggable' Myc-pathway genes.

Cancer Cell Int 2021 Apr 22;21(1):230. Epub 2021 Apr 22.

Department of Hematology, Children's Hospital of Soochow University, No.92 Zhongnan Street, SIP, Suzhou, 215003, Jiangsu, China.

Background: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease with a high risk of induction failure and poor outcomes, with relapse due to drug resistance. Recent studies show that bromodomains and extra-terminal (BET) protein inhibitors are promising anti-cancer agents. ARV-825, comprising a BET inhibitor conjugated with cereblon ligand, was recently developed to attenuate the growth of multiple tumors in vitro and in vivo. However, the functional and molecular mechanisms of ARV-825 in T-ALL remain unclear. This study aimed to investigate the therapeutic efficacy and potential mechanism of ARV-825 in T-ALL.

Methods: Expression of the BRD4 were determined in pediatric T-ALL samples and differential gene expression after ARV-825 treatment was explored by RNA-seq and quantitative reverse transcription-polymerase chain reaction. T-ALL cell viability was measured by CCK8 assay after ARV-825 administration. Cell cycle was analyzed by propidium iodide (PI) staining and apoptosis was assessed by Annexin V/PI staining. BRD4, BRD3 and BRD2 proteins were detected by western blot in cells treated with ARV-825. The effect of ARV-825 on T-ALL cells was analyzed in vivo. The functional and molecular pathways involved in ARV-825 treatment of T-ALL were verified by western blot and chromatin immunoprecipitation (ChIP).

Results: BRD4 expression was higher in pediatric T-ALL samples compared with T-cells from healthy donors. High BRD4 expression indicated a poor outcome. ARV-825 suppressed cell proliferation in vitro by arresting the cell cycle and inducing apoptosis, with elevated poly-ADP ribose polymerase and cleaved caspase 3. BRD4, BRD3, and BRD2 were degraded in line with reduced cereblon expression in T-ALL cells. ARV-825 had a lower IC50 in T-ALL cells compared with JQ1, dBET1 and OTX015. ARV-825 perturbed the H3K27Ac-Myc pathway and reduced c-Myc protein levels in T-ALL cells according to RNA-seq and ChIP. In the T-ALL xenograft model, ARV-825 significantly reduced tumor growth and led to the dysregulation of Ki67 and cleaved caspase 3. Moreover, ARV-825 inhibited cell proliferation by depleting BET and c-Myc proteins in vitro and in vivo.

Conclusions: BRD4 indicates a poor prognosis in T-ALL. The BRD4 degrader ARV-825 can effectively suppress the proliferation and promote apoptosis of T-ALL cells via BET protein depletion and c-Myc inhibition, thus providing a new strategy for the treatment of T-ALL.
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http://dx.doi.org/10.1186/s12935-021-01908-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061034PMC
April 2021

The advantage of chimeric antigen receptor T cell therapy in pediatric acute lymphoblastic leukemia with E2A-HLF fusion gene positivity: a case series.

Transl Pediatr 2021 Mar;10(3):686-691

Department of Hematology & Oncology, Children's Hospital of Soochow University, Suzhou, China.

The E2A-HLF fusion gene is a very poor biomarker in acute lymphoblastic leukemia (ALL) because of its high relapse risk, even with the most intensive chemotherapy and hematopoietic stem cell transplantation (HSCT). Here, we analyzed four cases diagnosed with E2A-HLF fusion gene-positive B-ALL and treated with the CCCG-ALL-2015 protocol based on high-risk stratification from Jun 2017 to May 2020 retrospectively. Three cases (Case 1, 2, 3) were insensitive to conventional therapy and inhibitors with high-level MRD on days 19 and 46, but they all achieved complete remission at the molecular level with Chimeric Antigen Receptor (CAR) T cell therapy regardless of primary resistance or recurrence. Although remission was initially achieved for Case 4, chemotherapeutics was not sensitive after recurrence. However, CAR-T cell therapy gave him the chance to obtain complement remission again. Cytokine release syndrome (CRS) with fever, chills, acute kidney injury, hypotension and capillary leak syndrome and CAR-T related encephalopathy syndrome (CRE) with seizures and encephaledema occurred after CAR-T cell therapy, but symptoms disappeared with effective intensive care. Overall, CAR-T cell therapy enabled the patients to achieve complement remission with controllable adverse events. Our results indicated that CAR-T cell therapy is a feasible and effective therapy for patients with E2A-HLF-positive B-ALL and prompted the authors to report these cases.
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http://dx.doi.org/10.21037/tp-20-323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041607PMC
March 2021

Photochemical reactions between superoxide ions and 2,4,6-trichlorophenol in atmospheric aqueous environments.

Chemosphere 2021 Apr 9;279:130537. Epub 2021 Apr 9.

School of Resource and Environmental Engineering, Hefei University of Technology, Hefei, 230009, PR China; Institute of Atmospheric Environment & Pollution Control, Hefei University of Technology, Hefei, 230009, PR China; Key Laboratory of Nanominerals and Pollution Control of Anhui Higher Education Institutes, Hefei University of Technology, Hefei, 230009, PR China. Electronic address:

The superoxide anion radical (O) is an important reactive oxygen species (ROS), and participates in several chemical reactions and biological processes. In this report, O was produced by irradiating riboflavin in an O-saturated solution by ultraviolet light with a maximum emission at 365 nm. And the contribution of O to 2, 4, 6-trichlorophenol (2, 4, 6-TCP) was investigated by a combination of laser flash photolysis (LFP) and UV light steady irradiation technique. The results of steady-state experiments showed that the photochemical decomposition efficiency of 2, 4, 6-TCP decreased with the increase of the initial concentration of TCP, while the increase of pH and riboflavin concentration promoted the photochemical reaction. The second-order rate constant of the reaction of the superoxide anion radical with 2, 4, 6-TCP phenoxyl radical (TCP) was (9.9 ± 0.9) × 10 L mol s determined by laser flash photolysis techniques. The dechlorination efficiency was 61.5% after illuminating the mixed solution with UV light for 2 h. The conversion of 2, 4, 6-trichlorophenol was accompanied by the reductive dechlorination process induced by superoxide ions. The main steady products of the photochemical reaction of 2, 4, 6-TCP with O were 2, 6-dichlorophenol (DCP), 2, 6-dichloro-1, 4-benzoquinone (DCQ) and 2, 6-dichlorohydroquinone (DCHQ). The addition process was the preferred process in the total reaction of superoxide ions with 2, 4, 6-TCP phenoxyl radical. These results indicated that the reaction of 2, 4, 6-TCP with O was a potential conversion pathway and contribute to atmospheric aqueous phase chemistry.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130537DOI Listing
April 2021

Medial Parabrachial Nucleus Is Essential in Controlling Wakefulness in Rats.

Front Neurosci 2021 25;15:645877. Epub 2021 Mar 25.

Department of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai, China.

Activation of the parabrachial nucleus (PB) in the brainstem induced wakefulness in rats, suggesting which is an important nucleus that controls arousal. However, the sub-regions of PB in regulating sleep-wake cycle is still unclear. Here, we employ chemogenetics and optogenetics strategies and find that activation of the medial part of PB (MPB), but not the lateral part, induces continuous wakefulness for 10 h without sleep rebound in neither sleep amount nor the power spectra. Optogenetic activation of glutamatergic MPB neurons in sleeping rats immediately wake rats mediated by the basal forebrain (BF) and lateral hypothalamus (LH), but not the ventral medial thalamus. Most importantly, chemogenetic inhibition of PB neurons decreases wakefulness for 10 h. Conclusively, these findings indicate that the glutamatergic MPB neurons are essential in controlling wakefulness, and that MPB-BF and MPB-LH pathways are the major neuronal circuits.
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http://dx.doi.org/10.3389/fnins.2021.645877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027131PMC
March 2021

Stimuli-responsive flexible membrane via co-assembling sodium alginate into assembly membranes of rod-like cellulose nanocrystals with an achiral array.

Carbohydr Polym 2021 Jun 17;262:117949. Epub 2021 Mar 17.

School of Chemistry and Chemical Engineering, and Chongqing Key Laboratory of Soft-Matter Material Chemistry and Function Manufacturing, Southwest University, Chongqing 400715, PR China; Joint International Research Laboratory of Biomass-Based Macromolecular Chemistry and Materials, Chongqing 400715, PR China. Electronic address:

Uniaxially assembling cellulose nanocrystals (CNCs) can induce strong solid-state emission based on optical inelastic scattering, whereas the CNC assembly membranes are not flexible enough for further applications. Thus, we introduced CNC into flexible sodium alginate (SA) and further controlled the assembly structure of CNC to increase the membrane toughness and maintain the emission properties. The results indicated that the stretchability increased from 0.027 % to 37 % when 33-37% when 33 % SA was introduced. The assembly achirality was controlled by tuning CNC concentration in suspension, and the co-assembly could further control the wavelength of the assembly-induced emission from 420 nm to 440 nm. Furthermore, the improved stretchability made assembly membrane an optical sensor, whose excitation wavelength blue-shifted about 30 nm under a 30 % strain. The emission of the co-assembly membrane could also respond to humidity, and this cellulose-based material should have great potential in biosensor and wearable devices.
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http://dx.doi.org/10.1016/j.carbpol.2021.117949DOI Listing
June 2021

Efficacy and safety of methylprednisolone against acute respiratory distress syndrome: A systematic review and meta-analysis.

Medicine (Baltimore) 2021 Apr;100(14):e25408

Intensive Care Unit, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.

Background: Acute respiratory distress syndrome (ARDS) is caused by an inflammatory injury to the lung. Dysregulated inflammation is the cardinal feature of ARDS. Methylprednisolone is an option for treating ARDS. However, the benefits and adverse effects of methylprednisolone have not been well assessed in patients with ARDS. This study aimed to evaluate the efficacy and safety of methylprednisolone against ARDS.

Material And Methods: The electronic database of Embase, PubMed, the Cochrane Library, CNKI, and Wanfang were searched, and randomized controlled trials (RCTs) reporting the efficacy and safety of methylprednisolone for ARDS were included. Revman 5.3 and Stata 15.0 were used to conduct the analysis. The fixed-effects model was used to calculate summary odds ratios (ORs) and 95% confidence interval (CIs).

Results: Ten RCTs studies involving 692 patients with ARDS. The summary results demonstrated that, compared with placebo, methylprednisolone had a statistically significant effect on mortality (OR = 0.64; 95% CI: 0.43-0.95, I2 = 42%); the time of mechanical ventilation (MD) = -2.70, 95% CI: -3.31 to -2.10; I2 = 0%) in patients with ARDS, but it was not associated with increased rates of adverse events (OR = 0.80; 95% CI: 0.34-1.86; I2 = 58%).

Conclusions: This systematic review and meta-analysis demonstrated that Methylprednisolone is safe against ARDS. It may reduce mortality and shorten the time of mechanical ventilation. However, well-designed and large-sample studies were required to fully characterize the efficacy and safety of methylprednisolone against ARDS.
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http://dx.doi.org/10.1097/MD.0000000000025408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036107PMC
April 2021

Alginate-Derived Mannuronate Oligosaccharide Attenuates Tauopathy through Enhancing Autophagy.

J Agric Food Chem 2021 Apr 8;69(15):4438-4445. Epub 2021 Apr 8.

Shenzhen Key Laboratory of Marine Bioresources and Ecology, and Guangdong Provincial Key Laboratory for Plant Epigenetics, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, PR China.

Polymannuronate (PM) is an acidic polysaccharide prepared from alginate, contained in edible brown seaweeds. An unsaturated mannuronate oligosaccharide (MOS) is an enzymatically depolymerized oligosaccharide prepared from PM. The effects of MOS on attenuating tauopathy were studied in HEK293/Tau cells and primary triple transgenic (3×Tg) neurons. MOS inhibited heparin-induced aggregation of the Tau-K18 oligomer and suppressed the levels of phosphorylated Tau protein. MOS treatment reduced the activity of glycogen synthase kinase-3β (GSK-3β) by decreasing its phosphorylation levels on the sites of Y216 and increasing phosphorylation levels on the sites of S9. MOS treatment increased the ratio of LC3-II/LC3-I levels and reduced the expression of p62, indicating an increase in autophagy. Finally, MOS-induced decrease in Tau protein expression was attenuated by the addition of an autophagy inhibitor, confirming the involvement of autophagy. These data support MOS as a promising functional food or potential pharmaceutics for attenuating Tau protein-related disease.
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http://dx.doi.org/10.1021/acs.jafc.1c00394DOI Listing
April 2021

Comment on: "The growth of teledermatology: Expanding to reach the underserved".

J Am Acad Dermatol 2021 Apr 3. Epub 2021 Apr 3.

Department of Dermatology, University of Connecticut Health Center, Farmington, Connecticut. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2021.03.100DOI Listing
April 2021

Detecting SARS-CoV-2 in the Breath of COVID-19 Patients.

Front Med (Lausanne) 2021 17;8:604392. Epub 2021 Mar 17.

Commune of Scientific Engineers, Institute of Physics, Chinese Academy of Sciences, Beijing, China.

In the COVID-19 outbreak year 2020, a consensus was reached on the fact that SARS-CoV-2 spreads through aerosols. However, finding an efficient method to detect viruses in aerosols to monitor the risk of similar infections and enact effective control remains a great challenge. Our study aimed to build a swirling aerosol collection (SAC) device to collect viral particles in exhaled breath and subsequently detect SARS-CoV-2 using reverse transcription polymerase chain reaction (RT-PCR). Laboratory tests of the SAC device using aerosolized SARS-CoV-2 pseudovirus indicated that the SAC device can produce a positive result in only 10 s, with a collection distance to the source of 10 cm in a biosafety chamber, when the release rate of the pseudovirus source was 1,000,000 copies/h. Subsequent clinical trials of the device showed three positives and 14 negatives out of 27 patients in agreement with pharyngeal swabs, and 10 patients obtained opposite results, while no positive results were found in a healthy control group ( = 12). Based on standard curve calibration, several thousand viruses per minute were observed in the tested exhalations. Furthermore, referring to the average tidal volume data of adults, it was estimated that an exhaled SARS-CoV-2 concentration of approximately one copy/mL is detectable for COVID-19 patients. This study validates the original concept of breath detection of SARS-CoV-2 using SAC combined with RT-PCR.
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http://dx.doi.org/10.3389/fmed.2021.604392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010128PMC
March 2021

[The Prognostic Factors for AML Children with CBFβ/MYH11 Positive].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021 Apr;29(2):369-373

Department of Hematology Jinan City People's Hospital, Jinan 271199, Shandong Province, China.

Objective: To analyze the prognostic factors of AML children with CBFβ/MYH11 positive.

Methods: Twenty-eight children with CBFβ/MYH11 positive treated in our hospital from May 2012 to June 2018 were selected, the clinical data and curative were analyzed and evaluated.

Results: Five-year OS and 5-year EFS rate of CBFβ/MYH11 positive AML children was 76.8% and 64.0% efficacy, respectively. Univariate analysis results showed that the OS rate of CBFβ/MYH11 positive AML children with WBC<60.0×10/L was 86.5%, which was significantly higher than those of CBFβ/MYH11 positive AML children with WBC≥60.0×10/L (χ=3.891, P<0.05). The EFS rate of CBFβ/MYH11 positive AML children with WBC<60.0×10/L was 76.0%, which was significantly higher than those of AML children with WBC≥60.0×10/L (χ=4.588, P<0.05). The EFS rate of CBFβ/MYH11 positive AML children with XRCC-Thr241Met wild type was 77.9%, which was significantly higher than those of AML children with XRCC-Thr241Met variant (χ=3.960, P<0.05). Cox multivariate survival analysis results showed that WBC level at initial diagnosis was the risk factor for OS rate. The WBC level and XRCC-Thr241Met type at initial diagnosis were the risk factors for EFS rate.

Conclusion: WBC level and XRCC-Thr241Met genotype at initial diagnosis are the major affecting factors for prognosis of AML children with CBFβ/MYH11 positive.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2021.02.010DOI Listing
April 2021

Mechanism of Resveratrol Dimers Isolated from Grape Inhibiting O Induced DNA Damage by UHPLC-QTOF-MS and UHPLC-QQQ-MS Analyses.

Biomedicines 2021 Mar 8;9(3). Epub 2021 Mar 8.

Xi'an Key Laboratory of Characteristic Fruit Storage and Preservation, Shaanxi Engineering Laboratory for Food Green Processing and Safety Control and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710119, China.

Resveratrol dimers have been extensively reported on due to their antioxidative activity. Previous studies revealed that resveratrol dimer has been shown to selectively quench singlet oxygen (O), and could protect DNA from oxidative damage. The mechanism of resveratrol dimers protecting DNA against oxidative damage is still not clear. Therefore, in this project, the reactants and products of resveratrol dimers protecting guanine from oxidative damage were qualitatively monitored and quantitatively analyzed by UHPLC-QTOF-MS and UHPLC-QQQ-MS. Results showed that when guanine and resveratrol dimers were attacked by O, mostly resveratrol dimers were oxidized, which protected guanine from oxidation. Resveratrol dimers' oxidation products were identified and quantified at 467.1134 [M-H] and 467.1118 [M-H], respectively. The resorcinol of resveratrol dimers reacted with singlet oxygen to produce p-benzoquinone, protecting guanine from O damage. Therefore, it is hereby reported for the first time that the resorcinol ring is the characteristic structure in stilbenes inhibiting O induced-DNA damage, which provides a theoretical basis for preventing and treating DNA damage-mediated diseases.
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http://dx.doi.org/10.3390/biomedicines9030271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999633PMC
March 2021

High Expression of Interleukin-3 Receptor Alpha Chain (CD123) Predicts Favorable Outcome in Pediatric B-Cell Acute Lymphoblastic Leukemia Lacking Prognosis-Defining Genomic Aberrations.

Front Oncol 2021 16;11:614420. Epub 2021 Mar 16.

Department of Hematology, Children's Hospital of Soochow University, Suzhou, China.

Background: Aberrant expression of CD123 (IL-3Rα) was observed in various hematological malignancies including acute lymphoblastic leukemia (ALL), which is the most common malignancy in childhood. Although widely used for minimal residual disease (MRD) monitoring, the prognostic value of CD123 has not been fully characterized in pediatric B-ALL. This retrospective study aims to evaluate the association between the CD123 expression of leukemic blasts and the outcomes of the pediatric B-ALL patients.

Methods: A total of 976 pediatric B-ALL, including 328 treated with CCLG-ALL-2008 protocol and 648 treated with CCCG-ALL-2015 protocol, were recruited in this retrospective study. CD123 expression was evaluated by flow cytometry. Patients with >50, 20-50, or <20% of CD123 expressing blasts were grouped into CD123, CD123, and CD123, respectively. The correlation between CD123 expression and the patients' clinical characteristics, overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS) were studied statistically.

Results: Of 976 pediatric B-ALL, 53.4% from the CCLG-ALL-2008 cohort and 49.2% from the CCCG-ALL-2015 cohort were CD123. In the CCLG-ALL-2008 cohort, CD123 was significantly associated with chromosome hyperdiploidy (p < 0.0001), risk stratification (p = 0.004), and high survival rate (p = 0.005). By comparing clinical outcomes, patients with CD123 displayed favorable prognosis, with a significantly better OS (p = 0.005), EFS (p = 0.017), and RFS (p = 0.045), as compared to patients with CD123 and CD123. The prognostic value of CD123 expression was subsequently confirmed in the CCCG-ALL-2015 cohort. Univariate and multivariate cox regression model analysis showed that high CD123 expression was independently associated with favorable EFS (OR: 0.528; 95% CI: 0.327 to 0.853; p = 0.009) in this cohort. In patients without prognosis-defining genomic abnormalities, high CD123 expression strongly indicated superior survival rates and was identified as an independent prognosis factor for EFS and RFS in both cohorts.

Conclusions: A group of B-ALL lacks prognosis-defining genomic aberrations, which proposes a challenge in risk stratification. Our findings revealed that high CD123 expression of leukemic blasts was associated with favorable clinical outcomes in pediatric B-ALL and CD123 could serve as a promising prognosis predictor, especially in patients without prognosis-defining genetic aberrations.
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http://dx.doi.org/10.3389/fonc.2021.614420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008053PMC
March 2021

Teleconnection between climate oscillations and riverine nutrient dynamics in Southeast China based on wavelet analysis.

Authors:
Yun Hao Jun Lu

Environ Sci Pollut Res Int 2021 Mar 31. Epub 2021 Mar 31.

Ministry of Education Key Laboratory of Environment Remediation and Ecological Health, Zhejiang University, Hangzhou, 310058, China.

Nonpoint source (NPS) pollution is mainly driven by hydrological processes; climate oscillation can affect regional water cycle processes. However, the relationship between climate oscillation and NPS pollution is still unclear, which increases the difficulty of water quality prediction and management. In this study, Mann-Kendall test and wavelet transform were adopted to investigate the teleconnection between ENSO (El Niño-Southern Oscillation) phenomenon and riverine NPS load dynamics in an agricultural watershed of Southeast China from 2003 to 2016. Results showed that annual precipitation, streamflow, and riverine nutrient load increased significantly during the study period. The change point for long-term riverine TN load and TP load appeared in 2009 and 2007, respectively. Rainfall, streamflow, nutrient loads, and Niño 3.4 sea temperature (SST) shared a common periodicity of 10-16 months. The southern oscillation index (SOI) and Niño 3.4 SST shared a common periodicity of 28-36 months. Moreover, Niño 3.4 SST showed a positive correlation with riverine nutrient loads at a periodicity of 10-16 months, while SOI showed a weakly negative correlation with riverine nutrient loads at a periodicity of 28-36 months. These findings indicate that the increasing frequency of warm ENSO events would enhance the risk of nutrient export to rivers in Southeast China and more attention should be paid to large-scale climate oscillation in the prediction of agricultural nutrient pollution and management of water quality in agricultural watersheds.
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http://dx.doi.org/10.1007/s11356-021-13715-xDOI Listing
March 2021

[Effects of acupuncture on Nod-like receptor protein 3 inflammasome signal pathway in the prefrontal cortex of rat with depression].

Zhen Ci Yan Jiu 2020 Oct;45(10):806-11

School of Acupuncture-moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing 100029, China.

Objective: To observe the influence of acupuncture on the expression of pivotal molecules of Nod-like receptor protein 3(NLRP3) inflammasome signal pathway in the prefrontal cortex of rats with depression, so as to explore the underlying mechanism of acupuncture on treatment of depression.

Methods: SD rats were randomly divided into 4 groups (8 rats/group),namely control, model, acupuncture and fluoxetine groups. The depression model was established by using chronic unpredictable mild stress for 6 weeks. During modeling, acupuncture (10 min)was applied to "Baihui"(GV20) and "Yintang"(EX-HN3) for rats of the acupuncture group once a day, with 1 day interval after consecutive 6 day-period for 36 days. Fluoxetine was given (10 mg/kg,1 mg/mL) by gavage to rats of the fluoxetine group every day during modeling for 42 days. The novelty-suppressed feeding test was used to observe feeding behavior of rats. The expressions of NLRP3 and apoptosis associated speck like protein containing a CARD (ASC), Caspase-1, and contents of IL-1β in the prefrontal cortex were detected by Western blot, immunohistoche-mistry and ELISA, separately.

Results: Compared with the control group, the latency of the novelty-suppressed feeding, and the expressions of NLRP3, ASC, Caspase-1 and IL-1β content in the prefrontal cortex of the model group were significantly increased (<0.01). Following the interventions, the latency of the noveltysuppressed feeding,and the expressions of NLRP3, ASC, Caspase-1 and IL-1β content in the prefrontal cortex in the acupuncture and fluoxetine groups were significantly decreased (<0.05,<0.01). There was no significant differences in the above indicators between the acupuncture group and the fluoxetine group (>0.05).

Conclusion: Acupuncture could inhibit the expression of NLRP3 inflammasome signal pathway in the pre-frontal cortex, and reduce the inflammation in the brain, which may mediate the anti-depressant effect of acupuncture.
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http://dx.doi.org/10.13702/j.1000-0607.200063DOI Listing
October 2020