Publications by authors named "Lin Tian"

487 Publications

Survival analysis of elderly patients over 65 years old with stage II/III gastric cancer treated with adjuvant chemotherapy after laparoscopic D2 gastrectomy: a retrospective cohort study.

BMC Cancer 2021 Feb 25;21(1):196. Epub 2021 Feb 25.

Department of General Surgery, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Ave, Guangzhou, 510-515, China.

Background: The benefits of adjuvant chemotherapy for elderly patients with gastric cancer (GC) remain unknown because elderly patients are underrepresented in most clinical trials. This study aimed to evaluate the effectiveness and complications of adjuvant chemotherapy in patients > 65 years of age after laparoscopic D2 gastrectomy.

Methods: This was a single-center retrospective cohort study of elderly patients (> 65 years) with stage II/III GC who underwent curative laparoscopic D2 gastrectomy with R0 resection between 2004 and 2018. The adjuvant chemotherapy regimens included monotherapy (oral capecitabine) and doublet chemotherapy (oral capecitabine plus intravenous oxaliplatin [XELOX] or intravenous oxaliplatin, leucovorin, and 5-fluorouracil [FOLFOX]). The data were retrieved from a prospectively registered database maintained at the Department of General Surgery in Nanfang Hospital, China. The patients were divided as surgery alone and surgery plus adjuvant chemotherapy (chemo group). The overall survival (OS), disease-free survival (DFS), chemotherapy duration, and toxicity were examined.

Results: There were 270 patients included: 169 and 101 in the surgery and chemo groups, respectively. There were 10 (10/101) and six (6/101) patients with grade 3+ non-hematological and hematological adverse events. The 1-/3-/5-year OS rates of the surgery group were 72.9%/51.8%/48.3%, compared with 90.1%/66.4%/48.6% for the chemo group (log-rank test: P = 0.018). For stage III patients, the 1-/3-/5-year OS rates of the surgery group were 83.7%/40.7%/28.7%, compared with 89.9%/61.2%/43.6% for the chemo group (log-rank test: P = 0.015). Adjuvant chemotherapy was significantly associated with higher OS (HR = 0.568, 95%CI: 0.357-0.903, P = 0.017) and DFS (HR = 0.511, 95%CI: 0.322-0.811, P = 0.004) in stage III patients.

Conclusions: This study suggested that adjuvant chemotherapy significantly improves OS and DFS compared with surgery alone in elderly patients with stage III GC after D2 laparoscopic gastrectomy, with a tolerable adverse event profile.
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http://dx.doi.org/10.1186/s12885-021-07919-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908711PMC
February 2021

Berberine elevates mitochondrial membrane potential and decreases reactive oxygen species by inhibiting the Rho/ROCK pathway in rats with diabetic encephalopathy.

Mol Pain 2021 Jan-Dec;17:1744806921996101

Department of Nuclear Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin, P.R. China.

Objectives: Diabetic encephalopathy (DE) is a serious complication of diabetes mainly occurring in the elderly patients. Berberine (BBR) is an isoquinoline alkaloids extracted from Coptis chinensis that is applied in the treatment of diabetes clinically. This study explored the possible mechanism of BBR in relieving DE.

Methods: Wistar rats were injected with streptozotocin and fed a high fat diet to establish the model of DE. The model rats were treated with BBR. The body weight, blood glucose and insulin of rats were measured, and Morris water maze test was conducted to evaluate the learning and memory abilities. The pathological conditions of cortical tissues were detected. The cortical mitochondria membrane potential (MMP) and reactive oxygen species (ROS) were monitored. The expressions of Rho/ROCK pathway-related genes of rat cortex were detected. The changes of MMP and ROS were detected after the treatment of Rho/ROCK pathway activator.

Results: The body weight of model rats changed little, and levels of blood glucose and insulin were increased. The spatial learning and memory abilities were impaired, with disordered cortical neurons, and obvious neurons apoptosis and glia proliferation. BBR alleviated cognitive dysfunction and pathological damage in rats with DE. BBR enhanced cortical MMP and suppressed ROS. BBR treatment inhibited the Rho/ROCK pathway. Activation of the Rho/ROCK pathway reversed the effects of BBR on MMP and ROS.

Conclusion: BBR elevated MMP and reduced ROS in rats with DE by inhibiting the Rho/ROCK pathway. This study may offer novel insights for the management of DE.
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http://dx.doi.org/10.1177/1744806921996101DOI Listing
February 2021

Schizophrenia polygenic risk scores in youth mental health: preliminary associations with diagnosis, clinical stage and functioning.

BJPsych Open 2021 Feb 22;7(2):e58. Epub 2021 Feb 22.

Youth Mental Health & Technology Team, Brain and Mind Centre, University of Sydney, Australia.

Background: The schizophrenia polygenic risk score (SCZ-PRS) is an emerging tool in psychiatry.

Aims: We aimed to evaluate the utility of SCZ-PRS in a young, transdiagnostic, clinical cohort.

Method: SCZ-PRSs were calculated for young people who presented to early-intervention youth mental health clinics, including 158 patients of European ancestry, 113 of whom had longitudinal outcome data. We examined associations between SCZ-PRS and diagnosis, clinical stage and functioning at initial assessment, and new-onset psychotic disorder, clinical stage transition and functional course over time in contact with services.

Results: Compared with a control group, patients had elevated PRSs for schizophrenia, bipolar disorder and depression, but not for any non-psychiatric phenotype (for example cardiovascular disease). Higher SCZ-PRSs were elevated in participants with psychotic, bipolar, depressive, anxiety and other disorders. At initial assessment, overall SCZ-PRSs were associated with psychotic disorder (odds ratio (OR) per s.d. increase in SCZ-PRS was 1.68, 95% CI 1.08-2.59, P = 0.020), but not assignment as clinical stage 2+ (i.e. discrete, persistent or recurrent disorder) (OR = 0.90, 95% CI 0.64-1.26, P = 0.53) or functioning (R = 0.03, P = 0.76). Longitudinally, overall SCZ-PRSs were not significantly associated with new-onset psychotic disorder (OR = 0.84, 95% CI 0.34-2.03, P = 0.69), clinical stage transition (OR = 1.02, 95% CI 0.70-1.48, P = 0.92) or persistent functional impairment (OR = 0.84, 95% CI 0.52-1.38, P = 0.50).

Conclusions: In this preliminary study, SCZ-PRSs were associated with psychotic disorder at initial assessment in a young, transdiagnostic, clinical cohort accessing early-intervention services. Larger clinical studies are needed to further evaluate the clinical utility of SCZ-PRSs, especially among individuals with high SCZ-PRS burden.
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http://dx.doi.org/10.1192/bjo.2021.14DOI Listing
February 2021

The treatment and rehabilitation of a critical COVID-19 case in China.

Clin Case Rep 2021 Feb 29;9(2):990-994. Epub 2020 Dec 29.

Department of Clinical Research Center Dazhou Central Hospital Dazhou China.

The lung lesions of this COVID-19 patient were slowly absorbed, and the clinical symptoms with shortness of breath were improved slowly in the recovery period.
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http://dx.doi.org/10.1002/ccr3.3725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869341PMC
February 2021

Correlation between apparent diffusion coefficient and pathological characteristics of patients with invasive breast cancer.

Ann Transl Med 2021 Jan;9(2):143

Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, China.

Background: There is insufficient research on the correlation between the apparent diffusion coefficient and clinicopathological characteristics of breast cancer patients. The present study is to investigate the correlation between the apparent diffusion coefficient and pathological characteristics of patients with invasive breast cancer.

Methods: From January 2019 to September 2020, 122 cases of invasive breast cancer and 21 cases of benign tumors were retrospectively enrolled. The apparent diffusion coefficient was compared between the two groups, and the correlation between the apparent diffusion coefficient and the pathological characteristics of the patients with invasive breast cancer were analyzed.

Results: Compared with the benign tumor group, the apparent diffusion coefficient in the invasive breast cancer group was significantly lower (0.89±0.17 1.47±0.27 10 mm/s, P=0.000). Using the apparent diffusion coefficient to diagnose patients with invasive breast cancer, the area under receiver operating characteristic (ROC) curve was 0.966±0.021 [95% confidence interval (CI): 0.924-1.000, P=0.000], and the best diagnostic cut-off value was 1.16 (10 mm/s), with sensitivity and specificity of 0.905 and 0.902, respectively. The apparent diffusion coefficient was used to diagnose vascular tumor thrombus in patients with invasive breast cancer. The area under the ROC curve was 0.641±0.068 (95% CI: 0.508-0.774, P=0.047), and the best diagnostic threshold was 0.835 (10 mm/s), with sensitivity and specificity of 0.676 and 0.650, respectively. The apparent diffusion coefficient in patients with high expression of Ki-67 (%) was significantly reduced (0.87±0.17 1.00±0.16 10 mm/s, P=0.000). The apparent diffusion coefficient was not significantly correlated with age, menopause, lesion size, estrogen receptor, progesterone receptor, or lymph node metastasis in patients with invasive breast cancer (P>0.05).

Conclusions: In patients with invasive breast cancer the apparent diffusion coefficient was significantly reduced. It was able to differentiate invasive breast cancer and vascular tumor thrombus, and was also related to Ki-67 (%) high expression.
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http://dx.doi.org/10.21037/atm-20-7746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867890PMC
January 2021

Analysis of common genetic variation and rare CNVs in the Australian Autism Biobank.

Mol Autism 2021 02 10;12(1):12. Epub 2021 Feb 10.

Mater Research Institute, The University of Queensland, Brisbane, QLD, Australia.

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition whose biological basis is yet to be elucidated. The Australian Autism Biobank (AAB) is an initiative of the Cooperative Research Centre for Living with Autism (Autism CRC) to establish an Australian resource of biospecimens, phenotypes and genomic data for research on autism.

Methods: Genome-wide single-nucleotide polymorphism genotypes were available for 2,477 individuals (after quality control) from 546 families (436 complete), including 886 participants aged 2 to 17 years with diagnosed (n = 871) or suspected (n = 15) ASD, 218 siblings without ASD, 1,256 parents, and 117 unrelated children without an ASD diagnosis. The genetic data were used to confirm familial relationships and assign ancestry, which was majority European (n = 1,964 European individuals). We generated polygenic scores (PGS) for ASD, IQ, chronotype and height in the subset of Europeans, and in 3,490 unrelated ancestry-matched participants from the UK Biobank. We tested for group differences for each PGS, and performed prediction analyses for related phenotypes in the AAB. We called copy-number variants (CNVs) in all participants, and intersected these with high-confidence ASD- and intellectual disability (ID)-associated CNVs and genes from the public domain.

Results: The ASD (p = 6.1e-13), sibling (p = 4.9e-3) and unrelated (p = 3.0e-3) groups had significantly higher ASD PGS than UK Biobank controls, whereas this was not the case for height-a control trait. The IQ PGS was a significant predictor of measured IQ in undiagnosed children (r = 0.24, p = 2.1e-3) and parents (r = 0.17, p = 8.0e-7; 4.0% of variance), but not the ASD group. Chronotype PGS predicted sleep disturbances within the ASD group (r = 0.13, p = 1.9e-3; 1.3% of variance). In the CNV analysis, we identified 13 individuals with CNVs overlapping ASD/ID-associated CNVs, and 12 with CNVs overlapping ASD/ID/developmental delay-associated genes identified on the basis of de novo variants.

Limitations: This dataset is modest in size, and the publicly-available genome-wide-association-study (GWAS) summary statistics used to calculate PGS for ASD and other traits are relatively underpowered.

Conclusions: We report on common genetic variation and rare CNVs within the AAB. Prediction analyses using currently available GWAS summary statistics are largely consistent with expected relationships based on published studies. As the size of publicly-available GWAS summary statistics grows, the phenotypic depth of the AAB dataset will provide many opportunities for analyses of autism profiles and co-occurring conditions, including when integrated with other omics datasets generated from AAB biospecimens (blood, urine, stool, hair).
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http://dx.doi.org/10.1186/s13229-020-00407-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874616PMC
February 2021

Vitamin-B12-conjugated PLGA-PEG nanoparticles incorporating miR-532-3p induce mitochondrial damage by targeting apoptosis repressor with caspase recruitment domain (ARC) on CD320-overexpressed gastric cancer.

Mater Sci Eng C Mater Biol Appl 2021 Jan 14;120:111722. Epub 2020 Nov 14.

Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address:

Among various methods, the use of targeting nucleic acid therapy is a promising method for inhibiting gastric cancer (GC) cells' rapid growth and metastasis abilities. In this study, vitamin B12-labeled poly (d,l-lactide-co-glycolide) and polyethylene glycol nanoparticles (PLGA-PEG-VB12 NPs) were developed for microRNAs-532-3p mimics incorporating as targeting gene delivery systems (miR-532-3p@PLGA-PEG-VB12 NPs) to fight against transcobalamin II (CD320)-overexpressed GC cells' progression. The PLGA-PEG-VB12 NPs with appropriate particle sizes and good bio-compatibility could be selectively delivered into CD320-overexpressed GC cells, and significantly decrease the expression of apoptosis repressor with caspase recruitment domain (ARC). Following that, more pro-apoptotic protein (Bax) flowed from cytoplasm into mitochondria to form Bax oligomerization, thus induced mitochondrial damage, including mitochondrial membrane potentials (MMPs) loss and excessive production of mitochondrial reactive oxygen species (mitoROS). Since that, mitochondrial permeability transition pore (mPTP) was opened, followed by induced more cytochrome c (Cyto C) releasing from mitochondria into cytosol, and finally activated caspase-depended cell apoptosis pathway. Therefore, our designed miR-532-3p@PLGA-PEG-VB12 NPs showed enhanced GC targeting ability, and could induce apoptosis through activating ARC/Bax/mitochondria-mediated apoptosis signaling pathway, finally remarkably suppressed proliferation of GC cells both in vitro and in vivo, which presented a promising treatment for GC.
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http://dx.doi.org/10.1016/j.msec.2020.111722DOI Listing
January 2021

LINC00460/DHX9/IGF2BP2 complex promotes colorectal cancer proliferation and metastasis by mediating HMGA1 mRNA stability depending on m6A modification.

J Exp Clin Cancer Res 2021 Feb 1;40(1):52. Epub 2021 Feb 1.

Cancer Institute, Xuzhou Medical University, 84 West Huaihai Road, Xuzhou, Jiangsu Province, 221002, China.

Background: Increasing studies have shown that long noncoding RNAs (lncRNAs) are pivotal regulators participating in carcinogenic progression and tumor metastasis in colorectal cancer (CRC). Although lncRNA long intergenic noncoding RNA 460 (LINC00460) has been reported in CRC, the role and molecular mechanism of LINC00460 in CRC progression still requires exploration.

Methods: The expression levels of LINC00460 were analyzed by using a tissue microarray containing 498 CRC tissues and their corresponding non-tumor adjacent tissues. The correlations between the LINC00460 expression level and clinicopathological features were evaluated. The functional characterization of the role and molecular mechanism of LINC00460 in CRC was investigated through a series of in vitro and in vivo experiments.

Results: LINC00460 expression was increased in human CRC, and high LINC00460 expression was correlated with poor five-year overall survival and disease-free survival. LINC00460 overexpression sufficiently induced the epithelial-mesenchymal transition and promoted tumor cell proliferation, migration, and invasion in vitro and tumor growth and metastasis in vivo. In addition, LINC00460 enhanced the protein expression of high-mobility group AT-hook 1 (HMGA1) by directly interacting with IGF2BP2 and DHX9 to bind the 3' untranslated region (UTR) of HMGA1 mRNA and increased the stability of HMGA1 mRNA. In addition, the N6-methyladenosine (m6A) modification of HMGA1 mRNA by METTL3 enhanced HMGA1 expression in CRC. Finally, it suggested that HMGA1 was essential for LINC00460-induced cell proliferation, migration, and invasion.

Conclusions: LINC00460 may be a novel oncogene of CRC through interacting with IGF2BP2 and DHX9 and bind to the m6A modified HMGA1 mRNA to enhance the HMGA1 mRNA stability. LINC00460 can serve as a promising predictive biomarker for the diagnosis and prognosis among patients with CRC.
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http://dx.doi.org/10.1186/s13046-021-01857-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851923PMC
February 2021

Investigation of the current situation of nipple-sparing mastectomy: a large multicenter study in China (CSBrs-003).

Chin Med J (Engl) 2021 Jan 19. Epub 2021 Jan 19.

Department of General Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China Department of General Surgery, Hainan Hospital of Chinese PLA General Hospital, Sanya, Hainan 572013, China Department of Thyroid and Breast Surgery, The First Peoples Hospital of Zunyi, Zunyi, Guizhou 563000, China Department of General Surgery, Beijing Shunyi Hospital, Beijing 101300, China Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.

Backgrounds: Mastectomy techniques have been extended to nipple-sparing mastectomy (NSM). This study aimed to assess the actual application of NSM in China and identify the factors influencing postoperative complications.

Methods: The clinical data of 615 patients (641 surgeries) undergoing NSM from January 1st, 2018 to December 31st, 2018 at 28 centers nationwide were retrospectively analyzed to obtain the rate of NSM and investigate factors related to NSM surgery.

Results: The proportion of NSM surgery performed in this study was 2.67% (17/641). Malignant breast tumors accounted for the majority of NSM surgery (559/641, 87.2%). A total of 475 (77.3%) patients underwent NSM combined with reconstructive surgery. The rate of reconstruction decreased with age in our study, and implants were the most common option (344/641, 53.7%) in reconstruction. Radial incision was the most selected method regardless of reconstruction. However, for those who underwent reconstruction surgery, 18.4% (85/462) of cases also chose curvilinear incision, while in the simple NSM surgery group, more patients chose circumareolar incision (26/136, 19.1%). The tumor-to-nipple distance (TND) influenced postoperative complications (P = 0.004). There were no relationships between postoperative complications and tumor size, tumor location, histologic grade, molecular subtype, nipple discharge, and axillary lymph nodes.

Conclusion: NSM surgery is feasible and only TND influenced postoperative complications of NSM surgery. But the proportion of NSM surgery performed is still low in nationwide centers of China. The selection criteria for appropriate surgical methods are important for NSM in clinical practice. To optimize clinical applications of NSM, further multicenter prospective randomized controlled studies are needed.

Trial Registration: ChiCTR.org.cn, ChiCTR1900027423; http://www.chictr.org.cn/showprojen.aspx?proj=38739.
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http://dx.doi.org/10.1097/CM9.0000000000001350DOI Listing
January 2021

Transport and deposition of ultrafine particles in the upper tracheobronchial tree: a comparative study between approximate and realistic respiratory tract models.

Comput Methods Biomech Biomed Engin 2021 Jan 7:1-10. Epub 2021 Jan 7.

Mechanical & Automotive Engineering, School of Engineering, RMIT University, Bundoora, VIC, Australia.

This paper presents a computational fluid dynamics (CFD) study of air-particle flows in the upper tracheobronchial tree. Two respiratory tract models, including a parametrically controlled approximate airway model developed by Kitaoka (KG model) and a CT-based patient specific airway (realistic model) were used. Assuming laminar, quasi-steady, three-dimensional air flow and spherical non-interacting ultrafine particles in sequentially bifurcating rigid bronchial airways, airflow patterns and particle transport/deposition in these two airway models were evaluated and compared. Overall deposition efficiency data was compared with the widely adopted ICRP data published by The International Commission on Radiological Protection. Good deposition efficiency agreements were observed between the present respiratory tract models and the ICRP data, which validated the numerical prediction accuracy of the present computational fluid-particle dynamics (CFPD) model. For the two respiratory models, the comparison showed both difference and similarity between the approximate KG model and the realistic model. Specifically, the realistic model showed more complicated airflow patterns due to the increased surface irregularity. The deposition efficiency data revealed a deposition preference in the first-generation airways compared to the rest regions. For ultrafine particles smaller than 10 nm, Brownian diffusion remains the dominant particle deposition mechanism. However, for ultrafine particles with size ranging from 10 nm to 100 nm, the deposition efficiency decreased dramatically with the 100 nm particles approaching to zero deposition in the present bronchial tree scope. The generation-by-generation deposition data presented in this paper is indispensable to the formulation of new lung inhalation exposure models.
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http://dx.doi.org/10.1080/10255842.2020.1869220DOI Listing
January 2021

Pica, Autism, and Other Disabilities.

Pediatrics 2021 Feb 6;147(2). Epub 2021 Jan 6.

National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia.

Background And Objectives: Pica, the repeated ingestion of nonfood items, can be life-threatening. Although case reports describe pica in children with autism spectrum disorder (ASD) or intellectual disability (ID), there has been little systematic study of pica prevalence. We assessed pica in children 30 to 68 months of age (median = 55.4 months) with and without ASD.

Methods: Our sample from the Study to Explore Early Development, a multisite case-control study, included children with ASD ( = 1426), children with other developmental disabilities (DDs) ( = 1735), and general population-based controls (POPs) ( = 1578). We subdivided the ASD group according to whether children had ID and the DD group according to whether they had ID and/or some ASD characteristics. Standardized developmental assessments and/or questionnaires were used to define final study groups, subgroups, and pica. We examined pica prevalence in each group and compared ASD and DD groups and subgroups to the POP group using prevalence ratios adjusted for sociodemographic factors.

Results: Compared with the prevalence of pica among POPs (3.5%), pica was higher in children with ASD (23.2%) and DD (8.4%), and in the following subgroups: ASD with ID (28.1%), ASD without ID (14.0%), DD with ID (9.7%), DD with ASD characteristics (12.0%), and DD with both ID and ASD characteristics (26.3%); however, pica prevalence was not elevated in children with DD with neither ID nor ASD characteristics (3.2%). Between-group differences remained after adjustment (adjusted prevalence ratio range 1.9-8.0, all <.05).

Conclusions: Pica may be common in young children with ASD, ASD characteristics, and ID. These findings inform the specialized health care needs of these children.
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http://dx.doi.org/10.1542/peds.2020-0462DOI Listing
February 2021

Cell-type-specific asynchronous modulation of PKA by dopamine in learning.

Nature 2021 02 23;590(7846):451-456. Epub 2020 Dec 23.

Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, MA, USA.

Reinforcement learning models postulate that neurons that release dopamine encode information about action and action outcome, and provide a teaching signal to striatal spiny projection neurons in the form of dopamine release. Dopamine is thought to guide learning via dynamic and differential modulation of protein kinase A (PKA) in each class of spiny projection neuron. However, the real-time relationship between dopamine and PKA in spiny projection neurons remains untested in behaving animals. Here we monitor the activity of dopamine-releasing neurons, extracellular levels of dopamine and net PKA activity in spiny projection neurons in the nucleus accumbens of mice during learning. We find positive and negative modulation of dopamine that evolves across training and is both necessary and sufficient to explain concurrent fluctuations in the PKA activity of spiny projection neurons. Modulations of PKA in spiny projection neurons that express type-1 and type-2 dopamine receptors are dichotomous, such that these neurons are selectively sensitive to increases and decreases, respectively, in dopamine that occur at different phases of learning. Thus, PKA-dependent pathways in each class of spiny projection neuron are asynchronously engaged by positive or negative dopamine signals during learning.
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http://dx.doi.org/10.1038/s41586-020-03050-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889726PMC
February 2021

Association between pica and gastrointestinal symptoms in preschoolers with and without autism spectrum disorder, Study to Explore Early Development.

Disabil Health J 2020 Dec 13:101052. Epub 2020 Dec 13.

National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA, USA.

Background: Pica, the repeated ingestion of nonfood items, can result in gastrointestinal (GI) outcomes. Children with autism spectrum disorder (ASD) and other developmental disabilities (DDs) are disproportionately affected by both pica and GI symptoms. Study of the inter-relationship between pica, GI symptoms, and ASD/DD is limited.

Objective/hypothesis: We assessed associations between pica and GI symptoms in preschool-aged children with and without ASD and other (non-ASD) DDs in the Study to Explore Early Development.

Methods: Our sample included children with ASD (n = 1244), other DDs (n = 1593), and population (POP) controls (n = 1487). Data to define final case-control status, pica, and GI symptoms were from standardized developmental assessments/questionnaires. Prevalence ratios, adjusted for sociodemographic factors (aPRs), and 95% confidence intervals were derived from modified Poisson regression.

Results: Within each group (ASD, DD, POP) and for the total sample, pica was associated with vomiting (aPR for total sample 2.6 [1.7, 4.0]), diarrhea (1.8 [1.4, 2.2]), and loose stools (1.8 [1.4, 2.2]). In the DD group, pica was associated with constipation (1.4 [1.03, 1.9]) and pain on stooling (1.8 [1.2, 2.6]). In analyses of the subgroup without pica, increases in GI symptoms were still evident in the ASD and DD groups compared to POP group.

Conclusion: These findings highlight an important adverse effect of pica, GI symptoms, in children with and without ASD and DDs; nonetheless, pica does not fully explain the increased risk for GI symptoms among children with ASD and DDs. These findings inform the specialized healthcare needs of children with ASD and other DDs.
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http://dx.doi.org/10.1016/j.dhjo.2020.101052DOI Listing
December 2020

Enhanced recovery after surgery in laparoscopic distal gastrectomy: Protocol for a prospective single-arm clinical trial.

J Minim Access Surg 2021 Jan-Mar;17(1):14-20

Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.

Background: The enhanced recovery after surgery (ERAS) programme is feasible and effective in reducing the length of hospital stay, overall complication rates and medical costs when applied to cases involving colonic and rectal resections. However, a recent prospective, randomised, open, parallel-controlled trial (Chinese Laparoscopic Gastrointestinal Surgery Study-01 trial), initiated by our team, indicated that under conventional peri-operative management, the reduction of the post-operative hospital stay of laparoscopic distal gastrectomy (LDG) is quite limited compared with open gastrectomy. Thus, if we could provide valuable clinical evidence for demonstrating the efficacy of the ERAS programme for gastric cancer patients undergoing LDG, it would significantly enhance the peri-operative management of gastrectomy and benefit the patients.

Methods: In this prospective single-arm trial, patients who are 18-75 years of age with gastric adenocarcinoma diagnosed with cT1-4aN0-3M0 and expected to undergo curative resection through LDG, are considered eligible for this study. All participants underwent LDG with peri-operative management under the ERAS programme. The primary outcome measures included the post-operative hospital stays and rehabilitative rate of the post-operative day 4. The secondary outcome measures are morbidity and mortality (time frame: 30 days), post-operative recovery index (time frame: 30 days), post-operative pain intensity (time frame: 3 days) and the medical costs from surgery to discharge.

Conclusion: With reasonable and scientific designing, the trial may be a great help to further discuss the benefit of ERAS programme and thus improving the peri-operative management of patients with gastrectomy.
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http://dx.doi.org/10.4103/jmas.JMAS_35_19DOI Listing
December 2020

Directed Evolution of a Selective and Sensitive Serotonin Sensor via Machine Learning.

Cell 2020 Dec 16;183(7):1986-2002.e26. Epub 2020 Dec 16.

Departments of Biochemistry and Molecular Medicine, Chemistry, Statistics, Molecular and Cellular Biology, and Physiology and Membrane Biology, the Center for Neuroscience, and Graduate Programs in Molecular, Cellular, and Integrative Physiology, Biochemistry, Molecular, Cellular and Developmental Biology and Neuroscience, University of California, Davis, Davis, CA 95616, USA. Electronic address:

Serotonin plays a central role in cognition and is the target of most pharmaceuticals for psychiatric disorders. Existing drugs have limited efficacy; creation of improved versions will require better understanding of serotonergic circuitry, which has been hampered by our inability to monitor serotonin release and transport with high spatial and temporal resolution. We developed and applied a binding-pocket redesign strategy, guided by machine learning, to create a high-performance, soluble, fluorescent serotonin sensor (iSeroSnFR), enabling optical detection of millisecond-scale serotonin transients. We demonstrate that iSeroSnFR can be used to detect serotonin release in freely behaving mice during fear conditioning, social interaction, and sleep/wake transitions. We also developed a robust assay of serotonin transporter function and modulation by drugs. We expect that both machine-learning-guided binding-pocket redesign and iSeroSnFR will have broad utility for the development of other sensors and in vitro and in vivo serotonin detection, respectively.
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http://dx.doi.org/10.1016/j.cell.2020.11.040DOI Listing
December 2020

Hormonal modulation of ESR1 mutant metastasis.

Oncogene 2021 Feb 15;40(5):997-1011. Epub 2020 Dec 15.

Lester & Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.

Estrogen receptor alpha gene (ESR1) mutations occur frequently in ER-positive metastatic breast cancer, and confer clinical resistance to aromatase inhibitors. Expression of the ESR1 Y537S mutation induced an epithelial-mesenchymal transition (EMT) with cells exhibiting enhanced migration and invasion potential in vitro. When small subpopulations of Y537S ESR1 mutant cells were injected along with WT parental cells, tumor growth was enhanced with mutant cells becoming the predominant population in distant metastases. Y537S mutant primary xenograft tumors were resistant to the antiestrogen tamoxifen (Tam) as well as to estradiol (E) withdrawal. Y537S ESR1 mutant primary tumors metastasized efficiently in the absence of E; however, Tam treatment significantly inhibited metastasis to distant sites. We identified a nine-gene expression signature, which predicted clinical outcomes of ER-positive breast cancer patients, as well as breast cancer metastasis to the lung. Androgen receptor (AR) protein levels were increased in mutant models, and the AR agonist dihydrotestosterone significantly inhibited estrogen-regulated gene expression, EMT, and distant metastasis in vivo, suggesting that AR may play a role in distant metastatic progression of ESR1 mutant tumors.
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http://dx.doi.org/10.1038/s41388-020-01563-xDOI Listing
February 2021

Theory-based Behavioral Predictors of Self-reported Use of Face Coverings in Public Settings during the COVID-19 Pandemic in the United States.

Ann Behav Med 2021 02;55(1):82-88

Office of the Director, National Center for Emerging and Zoonotic Infectious Diseases, CDC, Atlanta, GA.

Background: Investigating antecedents of behaviors, such as wearing face coverings, is critical for developing strategies to prevent SARS-CoV-2 transmission.

Purpose: The purpose of this study was to determine associations between theory-based behavioral predictors of intention to wear a face covering and actual wearing of a face covering in public.

Methods: Data from a cross-sectional panel survey of U.S. adults conducted in May and June 2020 (N = 1,004) were used to test a theory-based behavioral path model. We (a) examined predictors of intention to wear a face covering, (b) reported use of cloth face coverings, and (c) reported use of other face masks (e.g., a surgical mask or N95 respirator) in public.

Results: We found that being female, perceived importance of others wanting the respondent to wear a face covering, confidence to wear a face covering, and perceived importance of personal face covering use was positively associated with intention to wear a face covering in public. Intention to wear a face covering was positively associated with self-reported wearing of a cloth face covering if other people were observed wearing cloth face coverings in public at least "rarely" (aOR = 1.43), with stronger associations if they reported "sometimes" (aOR = 1.83), "often" (aOR = 2.32), or "always" (aOR = 2.96). For other types of face masks, a positive association between intention and behavior was only present when observing others wearing face masks "often" (aOR = 1.25) or "always" (aOR = 1.48).

Conclusions: Intention to wear face coverings and observing other people wearing them are important behavioral predictors of adherence to the CDC recommendation to wear face coverings in public.
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http://dx.doi.org/10.1093/abm/kaaa109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799273PMC
February 2021

Semi-centennial sediment records of HCHs and DDTs from the East China marginal seas: Role of lateral transport in catchment.

Chemosphere 2021 Jan 27;263:128100. Epub 2020 Aug 27.

Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention, Institute of Atmospheric Sciences, Department of Environmental Science and Engineering, Fudan University, Shanghai, 200433, China.

We reconstructed the history of the inputs of hexachlorocyclohexanes (HCHs) and dichlorodiphenyltrichloroethanes (DDTs) into the marine environment to reveal the time-dependent influence of sources and associated anthropogenic activities in China, based on Pb-dated cores from the East China marginal seas (ECMS). The temporal dynamics of pesticide contamination expresses as deposition fluxes, inventories, and half-life estimations varied among the cores, suggesting heterogeneity in transport pathways of pollutants. The depth profiles of pesticide inputs closely followed their historical production and application timelines in China, and were also affected by human activities in catchments, with general declines in HCH and DDT inputs to the coring sites after their peak deposition. Despite the prevalence of occurrence of weathered HCH/DDT in the cores, there were clear source-dependent differences in isomeric composition and accumulation between before and after these pesticides were banned. α-HCH and p,p'-DDT were relatively more enriched in sediments from the pre-ban period when heavy technical HCHs and DDTs use occurred, as indicated by the higher α-/β-HCH and lower (DDE + DDD)/DDTs ratios, and the larger fractions of α-HCH and p,p'-DDT influxes to the coring sites in the ΣHCH and ΣDDT fluxes, respectively, while this pattern shifted to be historical residue-based in the post-ban period. The difference in the recent influxes of pesticides to core sediments and their higher post-ban inventories highlight the increasing importance of historical sources over time and continuous input of weathered residues into marine environment via lateral transport.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128100DOI Listing
January 2021

Efficacy of dendritic cell-cytokine induced killer cells combined with concurrent chemoradiotherapy on locally advanced non-small cell lung cancer.

J BUON 2020 Sep-Oct;25(5):2364-2370

Department of Respirology, Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun 130021, China.

Purpose: To explore the efficacy and safety of docetaxel/cisplatin concurrent chemoradiotherapy (CCRT) combined with dendritic cell-cytokine induced killer cell (DC-CIK) immunotherapy in the treatment of locally advanced non-small cell lung cancer (LANSCLC).

Methods: The clinical data of 142 LANSCLC patients treated in our hospital from March 2014 to March 2016 were retrospectively analyzed. 71 patients were treated with docetaxel/cisplatin CCRT (CCRT group), while the remaining 71 patients underwent CCRT combined with DC-CIK immunotherapy (DC-CIK group). The clinical data of all patients were collected, the short-term efficacy, the changes in serum immunological indexes and quality of life before and after treatment, and the incidence of adverse reactions were compared between the two groups, and the overall survival (OS) and progression-free survival (PFS) were recorded during the follow-up of patients.

Results: After treatment, the level of cluster of differentiation 3+ (CD3+) CD4+ T lymphocytes, CD4/CD8 ratio and CD56+ natural killer (NK) cell ratio significantly rose, while the level of CD3+ CD8+ T lymphocytes significantly declined in both groups compared with those before treatment. After treatment, the level of CD3+ CD4+ T lymphocytes, CD4/CD8 ratio and CD56+ NK cell ratio were obviously higher, while the level of CD3+ CD8+ T lymphocytes was obviously lower in DC-CIK group than those in CCRT group. At 12 months after treatment, both Karnofsky performance scale (KPS) score and quality of life (QOL) score in DC-CIK group were evidently higher than those in CCRT group. In CCRT group and DC-CIK group, 1-year OS was 74.6% and 83.1%, and 1-year PFS was 70.4% and 73.2%, respectively. 2-year OS was 45.1% and 57.7%, and 2-year PFS was 38.0% and 46.5%), respectively. 3-year OS was 26.8% and 40.8%, and 3-year PFS was 15.5% and 22.5%, respectively. It can be seen that both OS and PFS in DC-CIK group were remarkably superior to those in CCRT group.

Conclusion: Docetaxel/cisplatin CCRT combined with DC-CIK can significantly enhance the cellular immunity, improve the long-term survival rate and raise the quality of life of LANSCLC patients, with tolerable adverse reactions.
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December 2020

Particulate and Dissolved Black Carbon in Coastal China Seas: Spatiotemporal Variations, Dynamics, and Potential Implications.

Environ Sci Technol 2021 Jan 4;55(1):788-796. Epub 2020 Dec 4.

College of Marine Ecology and Environment, Shanghai Ocean University, Shanghai 201306, China.

Elaborating the spatiotemporal variations and dynamic mechanisms of black carbon (BC) in coastal seas, the geographically pivotal intermediate zones that link the terrestrial and open oceanic ecosystems, will contribute significantly to refine the regional and global BC geochemistry. In this study, we implemented a large spatial-scale and multiseason and -layer seawater sampling campaign in high BC emission influenced coastal China seas (Bohai Sea and Northern Yellow Sea) and quantified the thermal/optical reflectance-based particulate BC (PBC) and benzene polycarboxylic acids-based dissolved BC (DBC). We found that the climate and its associated hydrological effects (including the intensive resuspension and coastal current transport) largely regulate both PBC and DBC spatiotemporal variations and dynamics. In combination with previous work on upstream rivers and downstream open ocean, a significant and continuous decrease in the DBC aromatic condensation was observed along the river-to-ocean continuum, probably due to the increment of the photochemical degradation during the waterborne transport. Based on our DBC methodological development, i.e., the determination and subsequent inclusion of the nitrated BC molecular markers, the magnitudes of the current global DBC fluxes and pools were updated. After the update, the DBC fluxes from atmospheric deposition and riverine delivery were estimated at rates of 4.3 and 66.3 Tg yr, respectively, and the global oceanic DBC pool was approximately 36 Gt. This update will greatly assist in constructing a more robust regional and global DBC and BC cycling and budgets.
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http://dx.doi.org/10.1021/acs.est.0c06386DOI Listing
January 2021

Occurrence, behavior, and fate of organophosphate esters (OPEs) in subtropical paddy field environment: A case study in Nanning City of South China.

Environ Pollut 2020 Dec 18;267:115675. Epub 2020 Sep 18.

College of Land and Environment, Shenyang Agricultural University, Shenyang, 110866, China.

Occurrence, behavior, and fate of 11 OPEs in multiple environmental matrices, which include air, rainwater, dustfall, paddy soil, irrigation water, and rice plants from nine subtropical paddy fields of South China, were investigated. The total concentrations of 11 OPEs (∑OPEs) in all matrices are generally higher in the urban areas than in rural areas, and they are higher in summer than in fall. However, both urban and rural areas showed a similar composition profile of OPEs, indicating that the OPEs come from similar sources in the two areas. Except for irrigation water, significant positive correlations of ∑OPEs were observed between air and the other five matrices. The exchange and partition of OPEs among air, soil, and water demonstrate that most of OPEs were transferred from air into water and soil, and from water into soil. Thus, the air may be an important source of OPEs in the paddy fields, and the soil may act as a principal environmental reservoir of OPEs. The contribution of air-soil exchange, atmospheric deposition (rainwater plus dustfall), and irrigation water to the total input fluxes of OPEs (2100 ± 980 ng/m/day) reached an average of 19%, 38% (37% + 1%), and 43%, respectively. The water (rainwater plus irrigation water) is the primary medium transferring the OPEs into the paddy fields and contributed to the input flux by 80%. Output flux of OPEs via mature rice plants was about 220 μg/m, 2% of which were presented in rice, and the remaining 98% may be re-released into the environment through the pathway of straw turnover or burning. Dietary exposure via rice was much higher than inhalation exposure, dust ingestion, and dermal absorption via dust. However, no data shows that all of the intakes via the four exposure pathways could cause the risks to human health at present.
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http://dx.doi.org/10.1016/j.envpol.2020.115675DOI Listing
December 2020

Exosomes derived from three-dimensional cultured human umbilical cord mesenchymal stem cells ameliorate pulmonary fibrosis in a mouse silicosis model.

Stem Cell Res Ther 2020 11 25;11(1):503. Epub 2020 Nov 25.

Department of Occupational and Environmental Health, School of Public Health, Capital Medical University, No. 10, Xitoutiao Youanmen Street, Beijing, 100069, China.

Background: Silicosis is an occupational respiratory disease caused by long-term excessive silica inhalation, which is most commonly encountered in industrial settings. Unfortunately, there is no effective therapy to delay and cure the progress of silicosis. In the recent years, stem cell therapy has emerged as an attractive tool against pulmonary fibrosis (PF) owing to its unique biological characteristics. However, the direct use of stem cells remains limitation by many risk factors for therapeutic purposes. The exclusive utility of exosomes secreted from stem cells, rather than cells, has been considered a promising alternative to overcome the limitations of cell-based therapy while maintaining its advantages.

Methods And Results: In this study, we first employed a three-dimensional (3D) dynamic system to culture human umbilical cord mesenchymal stem cell (hucMSC) spheroids in a microcarrier suspension to yield exosomes from serum-free media. Experimental silicosis was induced in C57BL/6J mice by intratracheal instillation of a silica suspension, with/without exosomes derived from hucMSC (hucMSC-Exos), injection via the tail vein afterwards. The results showed that the gene expression of collagen I (COL1A1) and fibronectin (FN) was upregulated in the silica group as compared to that in the control group; however, this change decreased with hucMSC-Exo treatment. The value of FEV0.1 decreased in the silica group as compared to that in the control group, and this change diminished with hucMSC-Exo treatment. These findings suggested that hucMSC-Exos could inhibit silica-induced PF and regulate pulmonary function. We also performed in vitro experiments to confirm these findings; the results revealed that hucMSC-Exos decreased collagen deposition in NIH-3T3 cells exposed to silica.

Conclusions: Taken together, these studies support a potential role for hucMSC-Exos in ameliorating pulmonary fibrosis and provide new evidence for improving clinical treatment induced by silica.
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http://dx.doi.org/10.1186/s13287-020-02023-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687745PMC
November 2020

The ubiquitin E3 ligase Nedd4-2 relieves mechanical allodynia through the ubiquitination of TRPA1 channel in db/db mice.

Eur J Neurosci 2020 Nov 25. Epub 2020 Nov 25.

Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe, Hyogo, Japan.

Neural precursor cell-expressed developmentally downregulated protein 4-2 (Nedd4-2) is a member of the E3 ubiquitin ligase family that is highly expressed in sensory neurons and involved in pain modulation via downregulation of ion channels in excitable membranes. Ubiquitination involving Nedd4-2 is regulated by adenosine monophosphate-activated protein kinase (AMPK), which is impaired in the dorsal root ganglion (DRG) neurons of db/db mice. AMPK negatively regulates the expression of transient receptor potential ankyrin 1 (TRPA1), a recognised pain sensor expressed on the membrane of DRG neurons, consequently relieving mechanical allodynia in db/db mice. Herein, we studied the involvement of Nedd4-2 in painful diabetic neuropathy and observed that Nedd4-2 negatively regulated diabetic mechanical allodynia. Nedd4-2 was co-expressed with TRPA1 in mouse DRG neurons. Nedd4-2 was involved in TRPA1 ubiquitination, this ubiquitination, as well as Nedd4-2-TRPA1 interaction, was decreased in db/db mice. Moreover, Nedd4-2 levels were decreased in db/db mice, while an abnormal intracellular distribution was observed in short-term high glucose-cultured DRG neurons. AMPK activators not only restored Nedd4-2 distribution but also increased Nedd4-2 expression. These findings demonstrate that Nedd4-2 is a potent regulator of TRPA1 and that the abnormal expression of Nedd4-2 in DRG neurons contributes to diabetic neuropathic pain.
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http://dx.doi.org/10.1111/ejn.15062DOI Listing
November 2020

Impact of diabetes on prognosis of gastric cancer patients performed with gastrectomy.

Chin J Cancer Res 2020 Oct;32(5):631-644

Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.

Objective: This study aimed to determine the impact of type 2 diabetes mellitus (T2DM) on clinical outcomes of gastric cancer (GC) patients and explore whether metformin use and good glycemic control could reverse it.

Methods: Clinicopathologic data of consecutive GC patients who underwent gastrectomy at Nanfang Hospital between October 2004 and December 2015 were included. Propensity score matching (PSM) was performed to balance the important factors of the disease status between non-T2DM and T2DM group. The last follow-up time was January 2019.

Results: A total of 1,692 eligible patients (1,621 non-T2DM 71 T2DM) were included. After PSM, non-T2DM group (n=139) and T2DM group (n=71) were more balanced in baseline variables. The 5-year cancer-specific survival (CSS) rate in T2DM group (47.0%) was inferior to that in non-T2DM group (58.0%), but did not reach statistical significance [hazard ratio (HR)=1.319, 95% confidence interval (95% CI): 0.868-2.005, P=0.192]. While the 5-year progress-free survival (PFS) rate of T2DM group (40.6%) is significantly worse than that in non-T2DM group (56.3%) (HR=1.516, 95% CI: 1.004-2.290, P=0.045). Univariate and multivariate analyses showed that T2DM was an independent risk factor for PFS but not for CSS. In T2DM group, metformin use subgroup was associated with superior 5-year CSS and PFS in compared with non-metformin use subgroup, although the difference was not statistically significant (5-year CSS: 48.0%. 45.4%, HR=0.680, 95% CI: 0.352-1.313, P=0.246; 5-year PFS: 43.5%. 35.7%, HR=0.763, 95% CI: 0.400-1.454, P=0.406). The 5-year CSS rate was 47.5% in good glycemic control subgroup and 44.1% in poor glycemic control subgroup (HR=0.826, 95% CI: 0.398-1.713, P=0.605). And both two subgroups yielded a similar 5-year PFS rate (42.2%. 36.3%, HR=0.908, 95% CI: 0.441-1.871, P=0.792).

Conclusions: DM promoted disease progress of GC after gastrectomy but had not yet led to the significant discrepancy of CSS. For GC patients with T2DM, metformin use was associated with superior survival but without statistical significance, while better glycemic control could not improve the prognosis.
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http://dx.doi.org/10.21147/j.issn.1000-9604.2020.05.08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666786PMC
October 2020

Numerical analysis of nanoparticle transport and deposition in a cynomolgus monkey nasal passage.

Int J Numer Method Biomed Eng 2021 Feb 3;37(2):e3414. Epub 2021 Jan 3.

Mechanical & Automotive Engineering, School of Engineering, RMIT University, Bundoora, Victoria, Australia.

Environmental exposure to toxic agents is commonly encountered by occupational and residential populations. However, in vivo exposure data in human subjects is limited by measurement and ethical restrictions. Monkey represents a suitable surrogate for human exposure studies, but the particle transport and deposition features in monkey airways are still not well understood. As a response to this research challenge, this paper presents a virtual exposure study that numerically investigated the nanoparticle transport process through a realistic cynomolgus monkey nasal airway. Particles with size of 1 nm to 1 μm were considered and the transport process was modelled by the Lagrangian discrete phase model. Overall and local deposition as well as particle dispersion along the airway were examined by using a variety of non-dimensional parameters including combined diffusion parameter, deposition enhancement factor and particle flux enhancement factor. Consistent deposition patterns were observed in present and literature nasal models. Most particles tended to pass the nasal airway through certain spatial regions, including the middle section of the nasal valve, the lower half of the middle coronal plane, and the central regions of the choana. While naturally inhaled nanoparticles can hardly be delivered to the olfactory region as it is located apart from the mainstream with high particle flux. Research findings provide insight into nanoparticle inhalation exposure characteristics in the monkey airway and can contribute in formulating data extrapolation schemes between monkey and human airways.
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http://dx.doi.org/10.1002/cnm.3414DOI Listing
February 2021

Pluripotent stem cell-derived CAR-macrophage cells with antigen-dependent anti-cancer cell functions.

J Hematol Oncol 2020 11 11;13(1):153. Epub 2020 Nov 11.

Center for Stem Cell and Regenerative Medicine, Department of Basic Medical Sciences, and The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.

The Chimera antigen receptor (CAR)-T cell therapy has gained great success in the clinic. However, there are still major challenges for its wider applications in a variety of cancer types including lack of effectiveness due to the highly complex tumor microenvironment, and the forbiddingly high cost due to the personalized manufacturing procedures. In order to overcome these hurdles, numerous efforts have been spent focusing on optimizing Chimera antigen receptors, engineering and improving T cell capacity, exploiting features of subsets of T cell or NK cells, or making off-the-shelf universal cells. Here, we developed induced pluripotent stem cells (iPSCs)-derived, CAR-expressing macrophage cells (CAR-iMac). CAR expression confers antigen-dependent macrophage functions such as expression and secretion of cytokines, polarization toward the pro-inflammatory/anti-tumor state, enhanced phagocytosis of tumor cells, and in vivo anticancer cell activity. This technology platform for the first time provides an unlimited source of iPSC-derived engineered CAR-macrophage cells which could be utilized to eliminate cancer cells.
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http://dx.doi.org/10.1186/s13045-020-00983-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656711PMC
November 2020

Snail-mediated partial epithelial mesenchymal transition augments the differentiation of local lung myofibroblast.

Chemosphere 2021 Mar 4;267:128870. Epub 2020 Nov 4.

Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, 100069, Beijing, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China. Electronic address:

The pathogenesis of pulmonary fibrosis diseases is considered to be related with environmental exposures, but the exact mechanism is unclear and there are no effective treatments. The contribution of epithelial-mesenchymal transition (EMT) to lung fibrosis has been controversial. It was found that partial EMT might play a vital role in renal fibrosis. We also found that partial EMT might be involved in fibrosis diseases. In this study, we used a silicosis animal model of pulmonary fibrosis to observe whether partial EMT existed in pulmonary fibrosis disease and a co-culture system culturing fibroblasts and alveolar epithelial cells stimulated by TGF-β1 to evaluate the probable effects of partial EMT, thus determined the probable role of partial EMT in pulmonary fibrosis diseases. In vivo, the results revealed that partial EMT might exist in silica-induced lung fibrosis model and Snail which is a potent EMT inducer was involved during the process. In vitro, a co-culture system was used to evaluate the effects of EMT in murine alveolar epithelial type II (ATII) cells on the activation of underlying murine lung fibroblasts into myofibroblasts. The results showed that epithelial cells undergoing EMT promoted the differentiation of lung myofibroblast and this epithelial-mesenchymal crosstalk was mainly controlled by Snail. Following Snail silencing the EMT and the activation of NIH-3T3 into myofibroblast were obviously inhibited. It indicated that targeting this novel Snail might be a viable strategy for the treatment of lung fibrosis diseases.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128870DOI Listing
March 2021

Distribution and gas-particle partitioning of polycyclic aromatic hydrocarbons over the East China Sea and Yellow Sea in spring: Role of atmospheric transport transition.

Sci Total Environ 2021 Mar 17;762:143071. Epub 2020 Oct 17.

Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention, Institute of Atmospheric Sciences, Department of Environmental Science and Engineering, Fudan University, Shanghai 200433, China; Institute of Eco-Chongming (IEC), Shanghai 200062, China. Electronic address:

To elucidate the variations in the East Asian monsoon system during seasonal changes and their impacts on continental outflow of polycyclic aromatic hydrocarbons (PAHs), sixteen integrated air samples were collected during a research cruise covering the Yellow Sea (YS) and East China Sea (ECS) in mid-spring of 2017. The concentrations of total suspended particle (TSP), aerosol-phase PAH fractions, ratios of organic to elemental carbon (OC/EC) and gas-particle partitioning of atmospheric PAHs exhibited clear regional differences associated with variations in the monsoon regime. The total concentrations of 16 USEPA priority PAHs (ΣPAHs) varied from 3.11 to 13.4 ng/m throughout the cruise, with medium-to-high molecular weight (MW) PAHs more enriched over the YS and north ECS than the south ECS. Together with the relatively low gaseous PAH fraction over the YS and north ECS (78 ± 4%) relative to the south ECS (95 ± 13%), this result indicates the pattern of regional atmospheric transport. The ratio of organic to elemental carbon varied significantly between the south ECS (lower than 4) and the YS and north ECS (greater than 4), indicating contributions from vehicle emissions and coal combustion or biomass burning, respectively, following different atmospheric input pathways of carbonaceous aerosols, as supported by backward trajectory analysis. Considering the gas-particle partitioning of PAHs, soot adsorption was the main partitioning mechanism in the study region; while high-MW PAHs in the YS and north ECS were influenced by both absorption and adsorption. The K absorption model provided better predictions for high-MW PAHs when continental air masses prevailed, despite underestimating the partition coefficients (k) of low-MW PAHs. Meanwhile, predicted k for medium MW PAHs was better estimated over the YS and ECS when K was included.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143071DOI Listing
March 2021

Genome-wide Meta-analysis Finds the ACSL5-ZDHHC6 Locus Is Associated with ALS and Links Weight Loss to the Disease Genetics.

Cell Rep 2020 Oct;33(4):108323

Maurice Wohl Clinical Neuroscience Institute, King's College London, Department of Basic and Clinical Neuroscience, London, UK; King's College Hospital, Bessemer Road, London SE5 9RS, UK.

We meta-analyze amyotrophic lateral sclerosis (ALS) genome-wide association study (GWAS) data of European and Chinese populations (84,694 individuals). We find an additional significant association between rs58854276 spanning ACSL5-ZDHHC6 with ALS (p = 8.3 × 10), with replication in an independent Australian cohort (1,502 individuals; p = 0.037). Moreover, B4GALNT1, G2E3-SCFD1, and TRIP11-ATXN3 are identified using a gene-based analysis. ACSL5 has been associated with rapid weight loss, as has another ALS-associated gene, GPX3. Weight loss is frequent in ALS patients and is associated with shorter survival. We investigate the effect of the ACSL5 and GPX3 single-nucleotide polymorphisms (SNPs), using longitudinal body composition and weight data of 77 patients and 77 controls. In patients' fat-free mass, although not significant, we observe an effect in the expected direction (rs58854276: -2.1 ± 1.3 kg/A allele, p = 0.053; rs3828599: -1.0 ± 1.3 kg/A allele, p = 0.22). No effect was observed in controls. Our findings support the increasing interest in lipid metabolism in ALS and link the disease genetics to weight loss in patients.
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http://dx.doi.org/10.1016/j.celrep.2020.108323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610013PMC
October 2020

Genome-wide Meta-analysis Finds the ACSL5-ZDHHC6 Locus Is Associated with ALS and Links Weight Loss to the Disease Genetics.

Cell Rep 2020 Oct;33(4):108323

Maurice Wohl Clinical Neuroscience Institute, King's College London, Department of Basic and Clinical Neuroscience, London, UK; King's College Hospital, Bessemer Road, London SE5 9RS, UK.

We meta-analyze amyotrophic lateral sclerosis (ALS) genome-wide association study (GWAS) data of European and Chinese populations (84,694 individuals). We find an additional significant association between rs58854276 spanning ACSL5-ZDHHC6 with ALS (p = 8.3 × 10), with replication in an independent Australian cohort (1,502 individuals; p = 0.037). Moreover, B4GALNT1, G2E3-SCFD1, and TRIP11-ATXN3 are identified using a gene-based analysis. ACSL5 has been associated with rapid weight loss, as has another ALS-associated gene, GPX3. Weight loss is frequent in ALS patients and is associated with shorter survival. We investigate the effect of the ACSL5 and GPX3 single-nucleotide polymorphisms (SNPs), using longitudinal body composition and weight data of 77 patients and 77 controls. In patients' fat-free mass, although not significant, we observe an effect in the expected direction (rs58854276: -2.1 ± 1.3 kg/A allele, p = 0.053; rs3828599: -1.0 ± 1.3 kg/A allele, p = 0.22). No effect was observed in controls. Our findings support the increasing interest in lipid metabolism in ALS and link the disease genetics to weight loss in patients.
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http://dx.doi.org/10.1016/j.celrep.2020.108323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610013PMC
October 2020