Publications by authors named "Lin Wen"

247 Publications

Genomic epidemiology and transmission dynamics of SARS-CoV-2 in congregate healthcare facilities in Santa Clara County, California.

Clin Infect Dis 2021 Jul 30. Epub 2021 Jul 30.

County of Santa Clara, Public Health Department, San Jose, California, USA.

Background: Outbreaks of SARS-CoV-2 in long term care facilities (LTCFs) cause significant morbidity and mortality. Mapping viral transmission within and between by combining genomic sequencing with epidemiologic investigations enables targeting infection control interventions.

Methods: We conducted weekly surveillance of residents and staff in LTCFs in Santa Clara County, CA with at least one confirmed COVID-19 case between March and July 2020. Positive samples were referred for whole genome sequencing. Epidemiological investigations and phylogenetic analyses of the largest outbreaks (>30 cases) were carried out in six LTCFs (Facilities A through F).

Results: Among the 61 LTCFs in the county, 41 had at least one confirmed case during the study period, triggering weekly SARS-CoV-2 testing. The six largest outbreaks accounted for 60% of cases and 90% of deaths in LTCFs, though the bed capacity of these facilities represents only 11% of the LTCF beds in the county. Phylogenetic analysis of 196 whole genome sequences recovered from those facilities showed that each outbreak was monophyletic, with staff and residents sharing a common viral lineage. Outbreak investigations revealed that infected staff members often worked at multiple facilities, and in one instance, a staff member infected while working in one facility was the likely index case in another.

Conclusions: We detected a pattern of rapid and sustained transmission after a single introduction of SARS-CoV-2 in six large LTCF outbreaks, with staff playing a key role in transmission within and between facilities. Infection control, testing, and occupational policies to reduce exposure and transmission risk for staff are essential components to keeping facility residents safe.
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http://dx.doi.org/10.1093/cid/ciab553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385848PMC
July 2021

The blood flow-klf6a-tagln2 axis drives vessel pruning in zebrafish by regulating endothelial cell rearrangement and actin cytoskeleton dynamics.

PLoS Genet 2021 Jul 28;17(7):e1009690. Epub 2021 Jul 28.

Key Laboratory for Biorheological Science and Technology of Ministry of Education, Bioengineering College of Chongqing University, Chongqing, China.

Recent studies have focused on capillary pruning in various organs and species. However, the way in which large-diameter vessels are pruned remains unclear. Here we show that pruning of the zebrafish caudal vein (CV) from ventral capillaries of the CV plexus in different transgenic embryos is driven by endothelial cell (EC) rearrangement, which involves EC nucleus migration, junction remodeling, and actin cytoskeleton remodeling. Further observation reveals a growing difference in blood flow velocity between the two vessels in CV pruning in zebrafish embryos. With this model, we identify the critical role of Kruppel-like factor 6a (klf6a) in CV pruning. Disruption of klf6a functioning impairs CV pruning in zebrafish. klf6a is required for EC nucleus migration, junction remodeling, and actin cytoskeleton dynamics in zebrafish embryos. Moreover, actin-related protein transgelin 2 (tagln2) is a direct downstream target of klf6a in CV pruning in zebrafish embryos. Together these results demonstrate that the klf6a-tagln2 axis regulates CV pruning by promoting EC rearrangement.
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http://dx.doi.org/10.1371/journal.pgen.1009690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318303PMC
July 2021

An analysis of the implementation effects of new paths and methods of occupational ethics education for medical students in higher vocational colleges.

Am J Transl Res 2021 15;13(6):6399-6406. Epub 2021 Jun 15.

The Office of Party and Government, Jiangxi Health Vocational College Nanchang, Jiangxi, China.

Objective: To investigate the implementation effects of new paths and methods of occupational ethics education for medical students in higher vocational colleges.

Methods: A total of 668 students in higher vocational colleges were selected as the study subjects, and divided into traditional group (n=349) and innovative group (n=319) in accordance with their grades. The data pertaining to the students' views on the educational model of medical and occupational ethics, occupational passion, spirit of occupational risk, occupational ethics and codes, and doctor-patient rights and obligations and communication abilities and skills in the two groups were compared, so as to explore the influences of new paths and methods of occupational ethics education on the occupational ethics of medical students in higher vocational colleges.

Results: The study results showed that the innovative group was significantly superior to the traditional group in the satisfaction with the courses of occupational ethics, pedagogical effects, occupational dedication and passion, doctor-patient communication ability, the fulfillment of doctor-patient rights and obligations, and the cognition of occupational ethics and codes ( < 0.05).

Conclusion: The implementation of innovative methods of occupational ethics education for medical students in higher vocational colleges can produce significant feedback effects. The improved teachers' abilities and pedagogical methods, innovative teaching approaches and optimized curriculum can effectively improve the occupational ethics of medical students in higher vocational colleges.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290793PMC
June 2021

Icotinib versus chemotherapy as adjuvant treatment for stage II-IIIA EGFR-mutant non-small-cell lung cancer (EVIDENCE): a randomised, open-label, phase 3 trial.

Lancet Respir Med 2021 09 21;9(9):1021-1029. Epub 2021 Jul 21.

Thoracic Surgery Department, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Background: Icotinib has provided survival benefits for patients with advanced, epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC). We aimed to compare icotinib with chemotherapy in patients with EGFR-mutant stage II-IIIA NSCLC after complete tumour resection. Here, we report the results from the preplanned interim analysis of the study.

Methods: In this multicentre, randomised, open-label, phase 3 trial done at 29 hospitals in China, eligible patients were aged 18-70 years, had histopathogically confirmed stage II-IIIA NSCLC, had complete resection up to 8 weeks before random assignment, were treatment-naive, and had confirmed activation mutation in exon 19 or exon 21 of the EGFR gene. Participants were randomly assigned (1:1) with an interactive web-based response system to receive either oral icotinib 125 mg thrice daily for 2 years or four 21-day cycles of intravenous chemotherapy (vinorelbine 25 mg/m on days 1 and 8 of each cycle plus cisplatin 75 mg/m on day 1 of each cycle for adenocarcinoma or squamous carcinoma; or pemetrexed 500 mg/m plus cisplatin 75 mg/m on day 1 every 3 weeks for non-squamous carcinoma). The primary endpoint was disease-free survival assessed in the full analysis set. Secondary endpoints were overall survival assessed in the full analysis set and safety assessed in all participants who received study drug. This trial is registered with ClinicalTrials.gov, NCT02448797.

Findings: Between June 8, 2015, and August 2, 2019, 322 patients were randomly assigned to icotinib (n=161) or chemotherapy (n=161); the full analysis set included 151 patients in the icotinib group and 132 in the chemotherapy group. Median follow-up in the full analysis set was 24·9 months (IQR 16·6-36·4). 40 (26%) of 151 patients in the icotinib group and 58 (44%) of 132 patients in the chemotherapy group had disease relapse or death. Median disease-free survival was 47·0 months (95% CI 36·4-not reached) in the icotinib group and 22·1 months (16·8-30·4) in the chemotherapy group (stratified hazard ratio [HR] 0·36 [95% CI 0·24-0·55]; p<0·0001). 3-year disease-free survival was 63·9% (95% CI 51·8-73·7) in the icotinib group and 32·5% (21·3-44·2) in the chemotherapy group. Overall survival data are immature with 14 (9%) deaths in the icotinib group and 14 (11%) deaths in the chemotherapy. The HR for overall survival was 0·91 (95% CI 0·42-1·94) in the full analysis set. Treatment-related serious adverse events occurred in two (1%) of 156 patients in the icotinib group and 19 (14%) of 139 patients in the chemotherapy group. No interstitial pneumonia or treatment-related death was observed in either group.

Interpretation: Our results suggest that compared with chemotherapy, icotinib significantly improves disease-free survival and has a better tolerability profile in patients with EGFR-mutant stage II-IIIA NSCLC after complete tumour resection.

Funding: Betta Pharmaceuticals TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S2213-2600(21)00134-XDOI Listing
September 2021

Venom-gland transcriptomic, venomic, and antivenomic profiles of the spine-bellied sea snake (Hydrophis curtus) from the South China Sea.

BMC Genomics 2021 Jul 8;22(1):520. Epub 2021 Jul 8.

Hangzhou Key Laboratory for Animal Adaptation and Evolution, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China.

Background: A comprehensive evaluation of the -omic profiles of venom is important for understanding the potential function and evolution of snake venom. Here, we conducted an integrated multi-omics-analysis to unveil the venom-transcriptomic and venomic profiles in a same group of spine-bellied sea snakes (Hydrophis curtus) from the South China Sea, where the snake is a widespread species and might generate regionally-specific venom potentially harmful to human activities. The capacity of two heterologous antivenoms to immunocapture the H. curtus venom was determined for an in-depth evaluation of their rationality in treatment of H. curtus envenomation. In addition, a phylogenetic analysis by maximum likelihood was used to detect the adaptive molecular evolution of full-length toxin-coding unigenes.

Results: A total of 90,909,384 pairs of clean reads were generated via Illumina sequencing from a pooled cDNA library of six specimens, and yielding 148,121 unigenes through de novo assembly. Sequence similarity searching harvested 63,845 valid annotations, including 63,789 non-toxin-coding and 56 toxin-coding unigenes belonging to 22 protein families. Three protein families, three-finger toxins (3-FTx), phospholipase A (PLA), and cysteine-rich secretory protein, were detected in the venom proteome. 3-FTx (27.15% in the transcriptome/41.94% in the proteome) and PLA (59.71%/49.36%) were identified as the most abundant families in the venom-gland transcriptome and venom proteome. In addition, 24 unigenes from 11 protein families were shown to have experienced positive selection in their evolutionary history, whereas four were relatively conserved throughout evolution. Commercial Naja atra antivenom exhibited a stronger capacity than Bungarus multicinctus antivenom to immunocapture H. curtus venom components, especially short neurotoxins, with the capacity of both antivenoms to immunocapture short neurotoxins being weaker than that for PLAs.

Conclusions: Our study clarified the venom-gland transcriptomic and venomic profiles along with the within-group divergence of a H. curtus population from the South China Sea. Adaptive evolution of most venom components driven by natural selection appeared to occur rapidly during evolutionary history. Notably, the utility of commercial N. atra and B. multicinctus antivenoms against H. curtus toxins was not comprehensive; thus, the development of species-specific antivenom is urgently needed.
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http://dx.doi.org/10.1186/s12864-021-07824-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268360PMC
July 2021

The impact of economic growth, FDI, and innovation on environmental efficiency of the logistics industry in provinces along the belt and road in China: An empirical study based on the panel Tobit model.

Sci Prog 2021 Apr-Jun;104(2):368504211018054

Business College, Jiangxi Institute of Applied Science and Technology, Nan Chang, Jiangxi, China.

Due to the high-quality development of the Chinese economy, the improvement of environmental efficiency in Chinese industries has become a significant task. Understanding the environmental efficiency of the logistics industry is essential for implementing effective environmental policies. This study aims to explore the impacts of economic growth, foreign direct investment (FDI), and innovation on the environmental efficiency of the logistics industry. In this paper, we apply the undesirable SBM model to calculate the environmental efficiency of the logistics industry and use the Tobit model to analyze the impacts of economic growth, foreign direct investment (FDI), and innovation on the environmental efficiency of the logistics industry in provinces along the Belt and Road in China from 2009 to 2018. Based on the results indicate the average environmental efficiency of the logistics industry in Chinese provinces along the Belt and Road is 0.7880, indicating that the environmental efficiency of the logistics industry was generally low in some regions along the belt and road. Innovation and FDI were found have a significant impact on the environmental efficiency, while economic growth fails to significantly impact on the environmental efficiency of the logistics industry in provinces along the Belt and Road. Therefore, we should encourage improvement of the level of environmental efficiency of the logistics industry. It is necessary to realize the co-ordinated development of the logistics industry and the environment through optimization of the development of innovation and transforming the FDI model in provinces along the Belt and Road.
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http://dx.doi.org/10.1177/00368504211018054DOI Listing
May 2021

Epidemiologic Findings from Case Investigations and Contact Tracing for First 200 Cases of Coronavirus Disease, Santa Clara County, California, USA.

Emerg Infect Dis 2021 05;27(5):1301-1308

In January 2020, Santa Clara County, California, USA, began identifying laboratory-confirmed coronavirus disease among residents. County staff conducted case and contact investigations focused on households and collected detailed case demographic, occupation, exposure, and outcome information. We describe the first 200 test-positive cases during January 31-March 20, 2020, to inform future case and contact investigations. Probable infection sources included community transmission (104 cases), known close contact with a confirmed case-patient (66 cases), and travel (30 cases). Disease patterns across race and ethnicity, occupational, and household factors suggested multiple infection risk factors. Disproportionately high percentages of case-patients from racial and ethnic subgroups worked outside the home (Hispanic [86%] and Filipino [100%]); household transmission was more common among persons from Vietnam (53%). Even with the few initial cases, detailed case and contact investigations of household contacts capturing occupational and disaggregated race and ethnicity data helped identify at-risk groups and focused solutions for disease control.
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http://dx.doi.org/10.3201/eid2705.204876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084524PMC
May 2021

[Effects of deep ploughing during the fallow period and soil moisture-based furrow sowing on water and nitrogen utilization of dryland wheat.]

Ying Yong Sheng Tai Xue Bao 2021 Apr;32(4):1307-1316

College of Agriculture, Shanxi Agricultural University, Jinzhong 030801, Shanxi, China.

To understand the effects of deep ploughing during the fallow period and soil moisture-based furrow sowing on the utilization of water and nitrogen in dryland wheat, a field experiment following split-plot design was carried out from 2016 to 2018 in Wenxi County of Shanxi Province, with deep ploughing during the fallow period and no-tillage as main plots and soil moisture-based furrow sowing and drilling sowing as sub-plots. The results showed that, compared with no-tillage treatment, deep ploughing during the fallow period significantly increased soil water storage efficiency (by 38.3%-42.2%), soil water consumption (by 9.2%-13.2%), and nitrogen accumulation in each growth period, which in turn increased the yield by 7.1%-12.0%, annual water use efficiency by 5.5%-14.0%, nitrogen fertilizer absorption efficiency by 4.4%-10.3%, and nitrogen fertilizer partial productivity by 7.1%-12.0%. Compared with the treatment of drilling sowing, the soil moisture-based furrow sowing increased the total water consumption during the growth period (by 2.0%-4.8%) and nitrogen accumulation in each growth period, increased the yield by 6.8%-12.4%, water use efficiency during the growth period by 4.5%-7.2%, nitrogen absorption efficiency by 4.4%-10.3%, nitrogen partial productivity by 6.9%-12.4%. In conclusion, deep ploughing during the fallow period and soil moisture-based furrow sowing in dryland wheat could promote the storage and utilization of natural precipitation, increase plant nitrogen accumulation, and facilitate high wheat yield.
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http://dx.doi.org/10.13287/j.1001-9332.202104.019DOI Listing
April 2021

Introduction, Transmission Dynamics, and Fate of Early Severe Acute Respiratory Syndrome Coronavirus 2 Lineages in Santa Clara County, California.

J Infect Dis 2021 07;224(2):207-217

Department of Laboratory Medicine, University of California, San Francisco, San Francisco, California, USA.

We combined viral genome sequencing with contact tracing to investigate introduction and evolution of severe acute respiratory syndrome coronavirus 2 lineages in Santa Clara County, California, from 27 January to 21 March 2020. From 558 persons with coronavirus disease 2019, 101 genomes from 143 available clinical samples comprised 17 lineages, including SCC1 (n = 41), WA1 (n = 9; including the first 2 reported deaths in the United States, with postmortem diagnosis), D614G (n = 4), ancestral Wuhan Hu-1 (n = 21), and 13 others (n = 26). Public health intervention may have curtailed the persistence of lineages that appeared transiently during February and March. By August, only D614G lineages introduced after 21 March were circulating in Santa Clara County.
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http://dx.doi.org/10.1093/infdis/jiab199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8135363PMC
July 2021

C0818, a novel curcumin derivative, induces ROS-dependent cytotoxicity in human hepatocellular carcinoma cells in vitro via disruption of Hsp90 function.

Acta Pharmacol Sin 2021 Apr 6. Epub 2021 Apr 6.

Department of Pharmacology, School of Pharmacy, Fujian Provincial Key Laboratory of Natural Medicine Pharmacology, Fujian Medical University, Fuzhou, 350122, China.

Heat shock protein 90 (Hsp90) is the most common molecular chaperone that controls the maturation of many oncoproteins critical in tumor development. Hsp90 has been considered as a promising target for cancer treatment, but the clinical significance of Hsp90 and the mechanisms of Hsp90 regulating the tumor-promoting effects in hepatocellular carcinoma (HCC) remain obscure. Previous studies have shown that curcumin, a polyphenol derived from the plant turmeric (Curcuma longa), inhibits tumor growth, which may provide an effective alternative therapy for HCC. Compared to curcumin, a novel derivative of curcumin, 3,5-(E)-Bis(3-methoxy-4-hydroxybenzal)-4-piperidinone hydrochloride (C0818) that is more potent in Hsp90 inhibition and antitumor activity. In this study, we investigated the effect of C0818 on HCC cells in vitro and its relation to Hsp90 inhibition. We showed that C0818 concentration-dependently inhibited the proliferation, the colony formation and induced apoptosis in HepG2 and Sk-Hep-1 cells. C0818 concentration-dependently inhibited DNA synthesis and induced G/M phase arrest in HepG2 and Sk-Hep-1 cells. We further demonstrated that C0818 induced ROS- and caspase-dependent apoptosis in HCC cells through the mitochondrial-mediated pathway. C0818 induced the degradation of Hsp90 client proteins as RAS, C-Raf, P-C-Raf, Erk, P-ERK, MEK, P-MEK, Akt and P-Akt, which led to subsequent inhibition of the RAS/RAF/MEK/ERK and PI3K/AKT pathways. We revealed that C0818 could inhibit the binding of Hsp90 with its clients without affecting their transcription, which subsequently induced the degradation of Hsp90 clients by the proteasome rather than the lysosome. These results are of potential importance for elucidating a novel Hsp90 inhibitor targeting HCC.
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http://dx.doi.org/10.1038/s41401-021-00642-3DOI Listing
April 2021

Effectiveness of Epidemic Preventive Policies and Hospital Strategies in Combating COVID-19 Outbreak in Taiwan.

Int J Environ Res Public Health 2021 03 26;18(7). Epub 2021 Mar 26.

Department of Nursing, Hsinchu MacKay Memorial Hospital, Hsinchu 30071, Taiwan.

(1) Background: The implementation of effective control measures in a timely fashion is crucial to control the epidemic outbreak of COVID-19. In this study, we aimed to analyze the control measures implemented during the COVID-19 outbreak, as well as evaluating the responses and outcomes at different phases for epidemic control in Taiwan. (2) Methods: This case study reviewed responses to COVID-19 and the effectiveness of a range of control measures implemented for epidemic control in Taiwan and assessed all laboratory-confirmed cases between 11 January until 20 December 2020, inclusive of these dates. The confirmation of COVID-19 infection was defined as the positive result of a reverse-transcriptase-polymerase-chain-reaction test taken from a nasopharyngeal swab. Test results were reported by the Taiwan Centers for Disease Control. The incidence rate, mortality rate, and testing rate were compiled, and the risk ratio was provided to gain insights into the effectiveness of prevention measures. (3) Results and Discussion: This study presents retrospective data on the COVID-19 incidence rate in Taiwan, combined with the vital preventive control measures, in a timeline of the early stage of the epidemic that occurred in Taiwan. The implementation of multiple strategy control measures and the assistance of technologies to control the COVID-19 epidemic in Taiwan led to a relatively slower trend in the outbreak compared to the neighboring countries. In Taiwan, 766 confirmed patients were included, comprised of 88.1% imported cases and 7.2% local transmission cases, within the studied period. The incidence rate of COVID-19 in Taiwan during the studied period was 32 per million people, with a mortality rate of 0.3 per million people. Our analysis showed a significantly raised incidence risk ratio in the countries of interest in comparison to Taiwan during the study period; in the range of 1.9 to 947.5. The outbreak was brought under control through epidemic policies and hospital strategies implemented by the Taiwan Government. (4) Conclusion: Taiwan's preventive strategies resulted in a drastically lower risk for Taiwan nationals of contracting COVID-19 when new pharmaceutical drug or vaccines were not yet available. The preventive strategies employed by Taiwan could serve as a guide and reference for future epidemic control strategies.
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http://dx.doi.org/10.3390/ijerph18073456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036933PMC
March 2021

Peptide-Functionalized Nanoparticles-Encapsulated Cyclin-Dependent Kinases Inhibitor Seliciclib in Transferrin Receptor Overexpressed Cancer Cells.

Nanomaterials (Basel) 2021 Mar 18;11(3). Epub 2021 Mar 18.

School of Pharmacy, College of Medicine, National Taiwan University, Taipei 10050, Taiwan.

Seliciclib, a broad cyclin-dependent kinases (CDKs) inhibitor, exerts its potential role in cancer therapy. For taking advantage of overexpressive transferrin receptor (TfR) on most cancer cells, T7 peptide, a TfR targeting ligand, was selected as a targeting ligand to facilitate nanoparticles (NPs) internalization in cancer cells. In this study, poly(d,l-lactide-co-glycolide) (PLGA) was conjugated with maleimide poly(ethylene glycol) amine (Mal-PEG-NH) to form PLGA-PEG-maleimide copolymer. The synthesized copolymer was used to prepare NPs for encapsulation of seliciclib which was further decorated by T7 peptide. The result shows that the better cellular uptake was achieved by T7 peptide-modified NPs particularly in TfR-high expressed cancer cells in order of MDA-MB-231 breast cancer cells > SKOV-3 ovarian cancer cells > U87-MG glioma cells. Both SKOV-3 and U87-MG cells are more sensitive to encapsulated seliciclib in T7-decorated NPs than to free seliciclib, and that IC values were lowered for encapsulated seliciclib.
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http://dx.doi.org/10.3390/nano11030772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003333PMC
March 2021

Emerging mechanisms of valproic acid-induced neurotoxic events in autism and its implications for pharmacological treatment.

Biomed Pharmacother 2021 May 16;137:111322. Epub 2021 Feb 16.

Key Lab of Cardiovascular and Cerebrovascular Medicine, Drug Target and Drug Discovery Center, School of Pharmacy, Nanjing Medical University, Nanjing, China; Institute of Brain Sciences, The Affiliated Nanjing Brain Hospital of Nanjing Medical University, Nanjing, China. Electronic address:

Autism spectrum disorder (ASD) is a sort of mental disorder marked by deficits in cognitive and communication abilities. To date no effective cure for this pernicious disease has been available. Valproic acid (VPA) is a broad-spectrum, antiepileptic drug, and it is also a potent teratogen. Epidemiological studies have shown that children exposed to VPA are at higher risk for ASD during the first trimester of their gestational development. Several animal and human studies have demonstrated important behavioral impairments and morphological changes in the brain following VPA treatment. However, the mechanism of VPA exposure-induced ASD remains unclear. Several factors are involved in the pathological phase of ASD, including aberrant excitation/inhibition of synaptic transmission, neuroinflammation, diminished neurogenesis, oxidative stress, etc. In this review, we aim to outline the current knowledge of the critical pathophysiological mechanisms underlying VPA exposure-induced ASD. This review will give insight toward understanding the complex nature of VPA-induced neuronal toxicity and exploring a new path toward the development of novel pharmacological treatment against ASD.
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http://dx.doi.org/10.1016/j.biopha.2021.111322DOI Listing
May 2021

Effects of phosphorus fertilizer on root characteristics, uptake and utilization of phosphorus and yield of dryland wheat with contrasting yearly rainfall pattern.

Ying Yong Sheng Tai Xue Bao 2021 Mar;32(3):895-905

College of Agriculture, Shanxi Agricultural University, Jinzhong 030801, Shanxi, China.

To understand the growth responses of dryland wheat to different application rates of phosphorus fertilizer in different rainfall years, we examined root characteristics, spike number, yield and phosphate utilization. Results would help improve phosphate fertilizer use in dryland wheat production. We carried out a field experiment at the research station of Shanxi Agricultural University from 2012 to 2016. We examined the effects of four application rates of phosphorus (0, 75, 150 and 225 kg·hm on root growth, phosphate utilization and yield formation of dryland wheat in different years with contrasting rainfall pattern. Compared with the treatment without phosphorus fertilization, phosphate application increased root surface area at all growth stages and root weight density in the 0-80 cm soil layer at jointing, anthesis, and maturity stages. Phosphate application significantly increased soil water consumption from jointing to anthesis, and total soil water consumption in the growing season. Phosphate application enhanced the amount of pre-anthesis phosphate translocation and phosphate accumulation of grain. Spike number, yield and water use efficiency were increased with 75, 150 and 225 kg P·hm by 9.2% to 22.5%, 11.8% to 30.0%, and 2.1% to 12.1%, respectively. In the dry years, the application rates of 150 and 225 kg P·hm in comparison to 75 kg P·hm significantly increased root weight density and root surface area at all stages, soil water consumption from sowing to jointing and from jointing to anthesis, and total water consumption in the growing season. In comparison to the rate of 75 kg P·hm, 150 and 225 kg P·hm increased soil water consumption from sowing to jointing by 7.3-8.7 mm, soil water consumption from jointing to anthesis by 15.6-18.1 mm, and total water consumption by 15.6-18.1 mm. Significant increase in the pre-anthesis phosphate translocation and phosphate accumulation in grain was higher under 150 and 225 kg P·hm than that under 75 kg P·hm in dry years. Furthermore, the two rates (150 and 225 kg P·hm) in dry years increased spike number by 9.3%-10.7% and yield by 11.9%-14.6%. The application rate of 150 kg P·hm significantly improved phosphorus use efficiency by 20%-82% in comparison to other rates. In normal years, the rates of 150 and 225 kg P·hm increased root surface area, root weight density at both anthesis and maturity compared with 75 kg P·hm. Soil water consumption from anthesis to maturity and total soil water consumption in the growing season were also increased by 1.2-15.0 and 3.8-23.1 mm, respectively. In addition, phosphorus accumulation in post-anthesis and phosphate accumulation in grain were increased in both 150 and 225 kg P·hm, which increased spike number by 1.4%-9.6% and yield by 3.5%-10.4%. The effects of phosphate application at the rate of 150 kg P·hm were significantly different from 75 and 225 kg P·hm. In conclusion, phosphorus fertilizer application enhanced uptake of water and phosphate in dryland wheat at early and middle growth stages in dry years and at the late growth stage in normal years. Phosphorus application increased wheat yield mainly due to the increases of spike number. The application of 150 kg P·hm is the best choice for high water and phosphorus fertilizer use efficiency and high yield in both dry and normal years.
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http://dx.doi.org/10.13287/j.1001-9332.202103.006DOI Listing
March 2021

Nivolumab and Ipilimumab as Maintenance Therapy in Extensive-Disease Small-Cell Lung Cancer: CheckMate 451.

J Clin Oncol 2021 Apr 8;39(12):1349-1359. Epub 2021 Mar 8.

Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea.

Purpose: In extensive-disease small-cell lung cancer (ED-SCLC), response rates to first-line platinum-based chemotherapy are robust, but responses lack durability. CheckMate 451, a double-blind phase III trial, evaluated nivolumab plus ipilimumab and nivolumab monotherapy as maintenance therapy following first-line chemotherapy for ED-SCLC.

Methods: Patients with ED-SCLC, Eastern Cooperative Oncology Group performance status 0-1, and no progression after ≤ 4 cycles of first-line chemotherapy were randomly assigned (1:1:1) to nivolumab 1 mg/kg plus ipilimumab 3 mg/kg once every 3 weeks for 12 weeks followed by nivolumab 240 mg once every 2 weeks, nivolumab 240 mg once every 2 weeks, or placebo for ≤ 2 years or until progression or unacceptable toxicity. Primary end point was overall survival (OS) with nivolumab plus ipilimumab versus placebo. Secondary end points were hierarchically tested.

Results: Overall, 834 patients were randomly assigned. The minimum follow-up was 8.9 months. OS was not significantly prolonged with nivolumab plus ipilimumab versus placebo (hazard ratio [HR], 0.92; 95% CI, 0.75 to 1.12; = .37; median, 9.2 9.6 months). The HR for OS with nivolumab versus placebo was 0.84 (95% CI, 0.69 to 1.02); the median OS for nivolumab was 10.4 months. Progression-free survival HRs versus placebo were 0.72 for nivolumab plus ipilimumab (95% CI, 0.60 to 0.87) and 0.67 for nivolumab (95% CI, 0.56 to 0.81). A trend toward OS benefit with nivolumab plus ipilimumab was observed in patients with tumor mutational burden ≥ 13 mutations per megabase. Rates of grade 3-4 treatment-related adverse events were nivolumab plus ipilimumab (52.2%), nivolumab (11.5%), and placebo (8.4%).

Conclusion: Maintenance therapy with nivolumab plus ipilimumab did not prolong OS for patients with ED-SCLC who did not progress on first-line chemotherapy. There were no new safety signals.
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http://dx.doi.org/10.1200/JCO.20.02212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078251PMC
April 2021

Cadmium-induced dysfunction of the blood-brain barrier depends on ROS-mediated inhibition of PTPase activity in zebrafish.

J Hazard Mater 2021 06 21;412:125198. Epub 2021 Jan 21.

Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400030, China. Electronic address:

Increasing evidence has demonstrated that cadmium accumulation in the blood increases the risk of neurological diseases. However, how cadmium breaks through the blood-brain barrier (BBB) and is transferred from the blood circulation into the central nervous system is still unclear. In this study, we examined the toxic effect of cadmium chloride (CdCl) on the development and function of BBB in zebrafish. CdCl exposure induced cerebral hemorrhage, increased BBB permeability and promoted abnormal vascular formation by promoting VEGF production in zebrafish brain. Furthermore, in vivo and in vitro experiments showed that CdCl altered cell-cell junctional morphology by disrupting the proper localization of VE-cadherin and ZO-1. The potential mechanism involved in the inhibition of protein tyrosine phosphatase (PTPase) mediated by cadmium-induced ROS was confirmed with diphenylene iodonium (DPI), a ROS production inhibitor. Together, these data indicate that BBB is a critical target of cadmium toxicity and provide in vivo etiological evidence of cadmium-induced neurovascular disease in a zebrafish BBB model.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125198DOI Listing
June 2021

Subsoiling during summer fallow in rainfed winter-wheat fields enhances soil organic carbon sequestration on the Loess Plateau in China.

PLoS One 2021 27;16(1):e0245484. Epub 2021 Jan 27.

College of Agriculture, Shanxi Agricultural University, Taigu country, Shanxi, China.

Scientific management of the soil organic carbon (SOC) pool, e.g., through a reasonable tillage system, is a potential way to mitigate global climate change. There is scarce information about the effect of tillage during the summer fallow period on the SOC pool in rainfed winter-wheat fields. The present study was designed to evaluate the effects of tillage practices, i.e., plow tillage (PTF), subsoiling (STF) and no tillage (NTF), during the summer fallow period on SOC sequestration in winter-wheat fields in the rainfed area of the eastern Loess Plateau of China. The SOC, mineral-associated organic carbon (MOC), permanganate-oxidizable organic carbon (POxC) and particulate organic carbon (POC) concentrations were determined after four years of tillage implementation during the summer fallow period. Our results showed that in comparison to the adoption of NTF, the adoption of STF significantly increased POxC, POC and MOC concentrations by 56.6-111.2%, 45.7-118.7% and 26.2-29.4%, respectively, at the 10-20 and 30-40 cm soil depths before sowing (P < 0.05). The POxC and MOC concentrations under STF at depths of 0-10, 10-20, 20-30 and 30-50 cm were significantly greater than those under PTF and NTF after harvesting (P < 0.05). In addition, the SOC concentration and SOC stock under STF were significantly greater than those under NTF at the 0-10, 10-20, 20-30 and 30-40 cm soil depths before sowing and after harvesting (P < 0.05). Furthermore, in comparison to PTF and NTF, STF resulted in significantly higher SOC stocks by 12.0-25.3% and 7.1-19.2% than PTF and NTF, respectively, in the 0-10, 0-20, 0-30, 0-40 and 0-50 cm soil profiles at harvesting (P < 0.05). In summary, the adoption of STF could be beneficial to the management of the SOC pool in the 0-50 cm soil profile in the rainfed area of winter-wheat on the Loess Plateau of China.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245484PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840036PMC
June 2021

The complete chloroplast genome sequence of Lam. (Moringaceae).

Mitochondrial DNA B Resour 2019 Nov 18;4(2):4094-4095. Epub 2019 Nov 18.

Landscaping Company of Guangzhou, Guangzhou, Guangdong, China.

The plant family Moringaceae contains only one genus, , and is widely cultivated for its young seed pods and leaves used as vegetables and for traditional herbal medicine. In this study, we report the complete chloroplast genome of , assembled from whole-genome high-throughput sequencing reads, as a resource for future studies on the phylogeny and evolution of Moringaceae. The chloroplast genome was 160,600 bp in length, with a large single-copy (LSC) region of 88,577 bp, a small single-copy (SSC) region of 18,883 bp, separated by two inverted repeat (IR) regions of 26,570 bp each. It was predicted to contain 131 genes, with an overall GC content of 36.78%. Phylogenetic analysis of 71 protein-coding sequences of 13 plant plastomes showed that is closest to .
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http://dx.doi.org/10.1080/23802359.2019.1627922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687391PMC
November 2019

Visualizing subcellular rearrangements in intact β cells using soft x-ray tomography.

Sci Adv 2020 Dec 9;6(50). Epub 2020 Dec 9.

Department of Biological Sciences, Bridge Institute, USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA.

Characterizing relationships between cell structures and functions requires mesoscale mapping of intact cells showing subcellular rearrangements following stimulation; however, current approaches are limited in this regard. Here, we report a unique application of soft x-ray tomography to generate three-dimensional reconstructions of whole pancreatic β cells at different time points following glucose-stimulated insulin secretion. Reconstructions following stimulation showed distinct insulin vesicle distribution patterns reflective of altered vesicle pool sizes as they travel through the secretory pathway. Our results show that glucose stimulation caused rapid changes in biochemical composition and/or density of insulin packing, increased mitochondrial volume, and closer proximity of insulin vesicles to mitochondria. Costimulation with exendin-4 (a glucagon-like peptide-1 receptor agonist) prolonged these effects and increased insulin packaging efficiency and vesicle maturation. This study provides unique perspectives on the coordinated structural reorganization and interactions of organelles that dictate cell responses.
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http://dx.doi.org/10.1126/sciadv.abc8262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725475PMC
December 2020

Clonal Architecture of Mutation Predicts the Efficacy of EGFR-Tyrosine Kinase Inhibitors in Advanced NSCLC: A Prospective Multicenter Study (NCT03059641).

Clin Cancer Res 2021 02 13;27(3):704-712. Epub 2020 Nov 13.

Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, P.R. China.

Purpose: Clonal architecture is fundamental for the understanding of cancer biology and therapy; however, multiregional sampling in advanced-stage cancers is not always applicable. This prospective clinical trial was to investigate whether paired tissue and circulating tumor DNA (ctDNA) could describe the clonal architecture of advanced non-small cell lung cancer (NSCLC) and its association with clinical outcome (NCT03059641).

Patients And Methods: Paired tumor and plasma ctDNA samples were sequenced by target-capture deep sequencing of 1,021 genes. Clonal dominance analysis was performed on the basis of PyClone.

Results: Overall, 300 treatment-naïve patients with stage IIIB-IV NSCLC were recruited from 14 centers. Of the 94 patients with available ctDNA data for clonal architecture analysis, 72 (76.6%) showed as the dominant clone. The median progression-free survival was longer for these patients than for the 22 patients whose was nondominant clone [11 vs. 10 months; HR, 0.46; 95% confidence interval (CI), 0.24-0.88; = 0.02]. The difference was more significant if both tissue and ctDNA defined as dominant clone ( = 43) versus those not ( = 8; 11 vs. 6 months; HR, 0.13; 95% CI, 0.04-0.50; = 0.003). Moreover, multivariate Cox proportional HR analysis demonstrated clonal architecture as an independent prognostic indicator of the efficacy of EGFR-tyrosine kinase inhibitors (TKIs).

Conclusions: Paired tissue and ctDNA could be analyzed for clonal architecture in advanced cancer. mutations do not always make up a dominant clone in advanced NSCLC, which was associated with the efficacy of EGFR-TKIs in NSCLC.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-3063DOI Listing
February 2021

Survival Benefit and Genetic Profile of Pemetrexed as Initial Chemotherapy in Selected Chinese Patients With Advanced Lung Adenocarcinoma.

Front Oncol 2020 15;10:1568. Epub 2020 Sep 15.

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

This study investigated survival in selected Chinese patients with advanced lung adenocarcinoma who received initial chemotherapy with pemetrexed. We also explored the relationship between genetic biomarkers and pemetrexed efficacy. We retrospectively collected patients ( = 1,047) enrolled in the Chinese Patient Assistance Program from multiple centers who received pemetrexed alone or combined with platinum as initial chemotherapy and continued pemetrexed maintenance therapy for advanced lung adenocarcinoma from November 2014 to June 2017. The outcomes were duration of treatment (DOT) and overall survival (OS). Clinical features were analyzed for their influence on the treatment effect and prognosis. Next-generation sequencing (NGS) was performed to identify genetic biomarkers associated with the efficacy of pemetrexed. The median DOT was 9.1 months (95% CI: 8.5-9.8), and the median OS was 26.2 months (95% CI: 24.2-28.1). OS was positively correlated with DOT ( = 0.403, < 0.001). Multivariable analysis showed that smoking status and Eastern Cooperative Oncology Group (ECOG) performance status (PS) were independently associated with DOT; smoking status, ECOG PS, targeted therapy, and status were independently associated with OS. NGS in 22 patients with available samples showed genes with high mutation rates were: (54.5%), (50.0%), (18.2%), and (13.6%). When grouped based on progression-free survival (PFS) reported in the PARAMOUNT study, the DOT > 6.9 months set was associated with , and mutations, while mutation was observed only in the DOT ≤ 6.9 months set. This study shows that initial chemotherapy with pemetrexed is an effective regimen for advanced lung adenocarcinoma in selected Chinese patients. There is no specific genetic profile predicting the benefit of pemetrexed found by NGS. Biomarkers predicting the efficacy of pemetrexed need further exploration.
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http://dx.doi.org/10.3389/fonc.2020.01568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522477PMC
September 2020

Assessing the efficacy of a recombinant H9N2 avian influenza virus-inactivated vaccine.

Poult Sci 2020 Sep 24;99(9):4334-4342. Epub 2020 Jun 24.

College of Animal Science, South China Agricultural University, Guangzhou 510642, China; Key Laboratory of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou 510642, China; Key Laboratory of Animal Health Aquaculture and Environmental Control, Guangdong, Guangzhou 510642, China; Guangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, Guangzhou 510642, China; South China Collaborative Innovation Center for Poultry Disease Control and Product Safety, Guangzhou 510642, China. Electronic address:

The H9N2 avian influenza virus has been widely spread in poultry around the world. It is proved to the world that the avian influenza virus can directly infect human beings without any intermediate host adaptation in "1997 Hong Kong avian influenza case," which shows that the avian influenza virus not only causes significant losses to the poultry industry but also affects human health. In this study, we aimed to address the problem of low protection of avian H9N2 subtype influenza virus vaccine against H9N2 wild-type virus. We have rescued the H9.4.2.5 branched avian influenza virus isolated in South China by reverse genetics technology. We have recombined these virus (rHA/NA-GD37 and rHA/NA-GD38) which contain hemagglutinin and neuraminidase genes from the H9N2 avian influenza virus (MN064850 or MN064851) and 6 internal genes from the avian influenza virus (KY785906). We compared the biological properties of the virus for example virus proliferation, virus elution, thermostability, and pH stability. Then, we evaluated the immune effects between rHA/NA-GD37 and GD37, which show that the recombinant avian influenza virus-inactivated vaccine can stimulate chickens to produce higher antibody titers and produce little inflammatory response after the challenge. It is noticeable that the recombinant virus-inactivated vaccine had better immune impact than the wild-type inactivated vaccine. Generally speaking, this study provides a new virus strain for the development of a H9N2 vaccine.
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http://dx.doi.org/10.1016/j.psj.2020.06.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598126PMC
September 2020

Preparation and detection of sea snake antisera raised in rabbits.

Toxicon 2020 Oct 20;186:168-174. Epub 2020 Aug 20.

Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, 210023, Jiangsu, China; Hainan Key Laboratory of Herpetological Research, College of Fisheries and Life Sciences, Hainan Tropical Ocean University, Sanya, 572022, Hainan, China. Electronic address:

Antivenoms are currently the most effective medication used in the treatment of snakebites. However, there were relatively few studies on preparation of antivenoms targeting sea snakes, especially common sea snakes in China. In this study, we sought to prepare and detect mono- and bispecific antisera raised in rabbits against venoms of two sea snakes, Hydrophis cyanocinctus and H. curtus. The results of enzyme-linked immunosorbent assay showed that the rabbit antisera generally showed clearly detectable immunological cross-reactions after the third immunization and indicated that the strength of cross-reactions increased with an increase in the immunizing dose. Proteins within the H. cyanocinctus and H. curtus venoms showed similar profiles and were mainly concentrated in the low-molecular-weight region (8-25 kDa). Western blotting results revealed that the bands of these low-molecular weight proteins were dense and showed strong immunogenicity. Although we detected comparatively few bands of the high-molecular-weight proteins, these also showed strong immunogenicity. Our results indicate that both mono- and bispecific antisera both can neutralize H. cyanocinctus and H. curtus venoms, and in this regard, the monospecific H. curtus and bispecific antiserum were found to be superior to the H. cyanocinctus antiserum. Given the increasing frequency of snakebites worldwide, we believe that the findings of this study will have high practical applicability.
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http://dx.doi.org/10.1016/j.toxicon.2020.08.018DOI Listing
October 2020

IMI - Oral biopharmaceutics tools project - Evaluation of bottom-up PBPK prediction success part 4: Prediction accuracy and software comparisons with improved data and modelling strategies.

Eur J Pharm Biopharm 2020 Nov 14;156:50-63. Epub 2020 Aug 14.

Bristol-Myers Squibb, United Kingdom.

Oral drug absorption is a complex process depending on many factors, including the physicochemical properties of the drug, formulation characteristics and their interplay with gastrointestinal physiology and biology. Physiological-based pharmacokinetic (PBPK) models integrate all available information on gastro-intestinal system with drug and formulation data to predict oral drug absorption. The latter together with in vitro-in vivo extrapolation and other preclinical data on drug disposition can be used to predict plasma concentration-time profiles in silico. Despite recent successes of PBPK in many areas of drug development, an improvement in their utility for evaluating oral absorption is much needed. Current status of predictive performance, within the confinement of commonly available in vitro data on drugs and formulations alongside systems information, were tested using 3 PBPK software packages (GI-Sim (ver.4.1), Simcyp® Simulator (ver.15.0.86.0), and GastroPlus™ (ver.9.0.00xx)). This was part of the Innovative Medicines Initiative (IMI) Oral Biopharmaceutics Tools (OrBiTo) project. Fifty eight active pharmaceutical ingredients (APIs) were qualified from the OrBiTo database to be part of the investigation based on a priori set criteria on availability of minimum necessary information to allow modelling exercise. The set entailed over 200 human clinical studies with over 700 study arms. These were simulated using input parameters which had been harmonised by a panel of experts across different software packages prior to conduct of any simulation. Overall prediction performance and software packages comparison were evaluated based on performance indicators (Fold error (FE), Average fold error (AFE) and absolute average fold error (AAFE)) of pharmacokinetic (PK) parameters. On average, PK parameters (Area Under the Concentration-time curve (AUC), Maximal concentration (C), half-life (t)) were predicted with AFE values between 1.11 and 1.97. Variability in FEs of these PK parameters was relatively high with AAFE values ranging from 2.08 to 2.74. Around half of the simulations were within the 2-fold error for AUC and around 90% of the simulations were within 10-fold error for AUC. Oral bioavailability (F) predictions, which were limited to 19 APIs having intravenous (i.v.) human data, showed AFE and AAFE of values 1.37 and 1.75 respectively. Across different APIs, AFE of AUC predictions were between 0.22 and 22.76 with 70% of the APIs showing an AFE > 1. When compared across different formulations and routes of administration, AUC for oral controlled release and i.v. administration were better predicted than that for oral immediate release formulations. Average predictive performance did not clearly differ between software packages but some APIs showed a high level of variability in predictive performance across different software packages. This variability could be related to several factors such as compound specific properties, the quality and availability of information, and errors in scaling from in vitro and preclinical in vivo data to human in vivo behaviour which will be explored further. Results were compared with previous similar exercise when the input data selection was carried by the modeller rather than a panel of experts on each in vitro test. Overall, average predictive performance was increased as reflected in smaller AAFE value of 2.8 as compared to AAFE value of 3.8 in case of previous exercise.
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http://dx.doi.org/10.1016/j.ejpb.2020.08.006DOI Listing
November 2020

Nitrogen deposition reduces methane uptake in both the growing and non-growing season in an alpine meadow.

Sci Total Environ 2020 Dec 30;747:141315. Epub 2020 Jul 30.

China New Era Group Corporation, Beijing 100034, China.

Nitrogen (N) deposition-induced N input in alpine meadow soils may affect the soil exchange of methane (CH) with the atmosphere. The quantities and spatiotemporal variation in CH uptake remain largely unknown for this ecosystem on a global scale. Previous studies regarding CH flux have mainly focused on the growing season in alpine meadows. Thus, the impact of N deposition on the non-growing season uptake of CH is unknown. In this study, we investigated the effects of N deposition on CH uptake during both the growing and non-growing seasons in an alpine meadow on the central Qinghai-Tibet Plateau (QTP). The CH fluxes were measured using static chambers and gas chromatography in four N deposition treatment areas (Control; N7, 7 kg N ha yr; N20, 20 kg N ha yr; N40, 40 kg N ha yr) from May 2015 to August 2018. Our results showed that alpine meadow soils acted as CH sinks throughout the year. N deposition significantly decreased CH uptake fluxes (P < 0.05) and the annual mean CH uptake fluxes declined at N deposition levels of 7, 20, and 40 kg N ha yr by 12.3%, 14.4%, and 20.5%, respectively, compared with that of the control. Annual CH uptake was significantly correlated with total annual precipitation, mean annual air temperature, and N deposition rate. Annual cumulative CH uptake in the four treatments across 3 years was 75.1 mg C m, where approximately 40% of the total annual CH uptake occurred during the non-growing season. Our results showed that CH uptake in the non-growing season cannot be ignored when estimating annual uptake of CH because of the large CH uptake during the non-growing season in the alpine meadow on the QTP under N deposition conditions.
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http://dx.doi.org/10.1016/j.scitotenv.2020.141315DOI Listing
December 2020

Epidemiology of Malaria and Risk Factors for Severe Disease in Hubei Province, China.

Am J Trop Med Hyg 2020 10;103(4):1534-1539

Institute of Schistosomiasis Control, Hubei Provincial Center for Disease Control and Prevention, Wuhan, China.

This study aimed to describe the epidemiology of malaria and identify risk factors for severe disease in Hubei Province, China, using a case-based survey of retrospective data from 2013 to 2018. From 2013 to 2018, a total of 763 imported malaria cases were reported in Hubei Province; 69.2% (528/763) cases were caused by species. The proportion of malaria caused by increased from 66.7% in 2013 to 74.0% in 2018 (χ = 21.378, < 0.05). malaria was reported in 77 counties of Hubei Province. The majority of imported cases originated from Africa (98.9%, 522/528); 9.7% (51/528) of patients infected with developed severe malaria. Three deaths (case fatality rate: 0.6%) were related to imported malaria. Risk factors for severe malaria were being female (odds ratio [OR] = 3.593, 95% CI: 1.003-12.874), age ≥ 50 years (OR = 2.674, 95% CI: 1.269-5.634), > 3 days between symptom onset and diagnosis (OR = 2.383, 95% CI: 1.210-4.693), and the first-visit medical institution at the township level or lower (OR = 2.568, 95% CI: 1.344-4.908). Malaria prevention should be undertaken among high-risk groups, infection with should be detected early to prevent severe disease and death, and healthcare providers in health facilities at the township level should be trained on early recognition of malaria.
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http://dx.doi.org/10.4269/ajtmh.20-0299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543867PMC
October 2020

Characteristics of imported Plasmodium ovale spp. and Plasmodium malariae in Hubei Province, China, 2014-2018.

Malar J 2020 Jul 22;19(1):264. Epub 2020 Jul 22.

Institute of Parasitic Disease Control, Hubei Provincial Center for Disease Control and Prevention, Wuhan, 430079, China.

Background: There have been an increasing number of imported cases of malaria in Hubei Province in recent years. In particular, the number of cases of Plasmodium ovale spp. and Plasmodium malariae significantly increased, which resulted in increased risks during the malaria elimination phase. The purpose of this study was to acquire a better understanding of the epidemiological characteristics of P. ovale spp. and P. malariae imported to Hubei Province, China, so as to improve case management.

Methods: Data on all malaria cases from January 2014 to December 2018 in Hubei Province were extracted from the China national diseases surveillance information system (CNDSIS). This descriptive study was conducted to analyse the prevalence trends, latency periods, interval from onset of illness to diagnosis, and misdiagnosis of cases of P. ovale spp. and P. malariae malaria.

Results: During this period, 634 imported malaria cases were reported, of which 87 P. ovale spp. (61 P. ovale curtisi and 26 P. ovale wallikeri) and 18 P. malariae cases were confirmed. The latency periods of P. ovale spp., P. malariae, Plasmodium vivax, and Plasmodium falciparum differed significantly, whereas those of P. ovale curtisi and P. ovale wallikeri were no significant difference. The proportion of correct diagnosis of P. ovale spp. and P. malariae malaria cases were 48.3% and 44.4%, respectively, in the hospital or lower-level Centers for Disease Control and Prevention (CDC). In the Provincial Reference Laboratory, the sensitivity of microscopy and rapid diagnostic tests was 94.3% and 70.1%, respectively, for detecting P. ovale spp., and 88.9% and 38.9%, respectively, for detecting P. malariae. Overall, 97.7% (85/87) of P. ovale spp. cases and 94.4% (17/18) of P. malariae cases originated from Africa.

Conclusion: The increase in the number of imported P. ovale spp. and P. malariae cases, long latency periods, and misdiagnosis pose a challenge to this region. Therefore, more attention should be paid to surveillance of imported cases of P. ovale spp. and P. malariae infection to reduce the burden of public health and potential risk of malaria.
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http://dx.doi.org/10.1186/s12936-020-03337-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7374957PMC
July 2020

[Discussion on Standardization Management Mode of Medical Equipment Based on Whole Process Quality Control].

Zhongguo Yi Liao Qi Xie Za Zhi 2020 Mar;44(3):270-275

Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, 610072.

This paper introduced the current situation of medical equipment. Based on the current problems such as technology assessment difficulty, weak consciousness on maintenance management, less quality control during clinic use and backward information level, the standardized management based on the whole process quality control was proposed. Combined the whole process quality control system with the construction of quality management information, the management level of the medical equipment was enhanced. The application of standardized management based on the whole process quality control can make the medical equipment work better in the clinic and set a good foundation for the development of hospital.
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http://dx.doi.org/10.3969/j.issn.1671-7104.2020.03.018DOI Listing
March 2020

Rapid Sentinel Surveillance for COVID-19 - Santa Clara County, California, March 2020.

MMWR Morb Mortal Wkly Rep 2020 Apr 10;69(14):419-421. Epub 2020 Apr 10.

On February 27, 2020, the Santa Clara County Public Health Department (SCCPHD) identified its first case of coronavirus disease 2019 (COVID-19) associated with probable community transmission (i.e., infection among persons without a known exposure by travel or close contact with a patient with confirmed COVID-19). At the time the investigation began, testing guidance recommended focusing on persons with clinical findings of lower respiratory illness and travel to an affected area or an epidemiologic link to a laboratory-confirmed COVID-19 case, or on persons hospitalized for severe respiratory disease and no alternative diagnosis (1). To rapidly understand the extent of COVID-19 in the community, SCCPHD, the California Department of Public Health (CDPH), and CDC began sentinel surveillance in Santa Clara County. During March 5-14, 2020, four urgent care centers in Santa Clara County participated as sentinel sites. For this investigation, county residents evaluated for respiratory symptoms (e.g., fever, cough, or shortness of breath) who had no known risk for COVID-19 were identified at participating urgent care centers. A convenience sample of specimens that tested negative for influenza virus was tested for SARS-CoV-2 RNA. Among 226 patients who met the inclusion criteria, 23% had positive test results for influenza. Among patients who had negative test results for influenza, 79 specimens were tested for SARS-CoV-2, and 11% had evidence of infection. This sentinel surveillance system helped confirm community transmission of SARS-CoV-2 in Santa Clara County. As a result of these data and an increasing number of cases with no known source of transmission, the county initiated a series of community mitigation strategies. Detection of community transmission is critical for informing response activities, including testing criteria, quarantine guidance, investigation protocols, and community mitigation measures (2). Sentinel surveillance in outpatient settings and emergency departments, implemented together with hospital-based surveillance, mortality surveillance, and serologic surveys, can provide a robust approach to monitor the epidemiology of COVID-19.
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http://dx.doi.org/10.15585/mmwr.mm6914e3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147906PMC
April 2020

Natural killer cells in the pathogenesis of preeclampsia: a double-edged sword.

J Matern Fetal Neonatal Med 2020 Mar 19:1-8. Epub 2020 Mar 19.

Department of Obstetrics and Gynecology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China.

To investigate the relationship between natural killer (NK) cells, extravillous trophoblast cells (EVTs) and vessel remodeling in early human pregnancy, and the association between NK cells and preeclampsia (PE) in late human pregnancy. Human decidual tissues from women with normal pregnancies were collected and examined for the relationship of NK cells with uterine vessel remodeling using immunohistochemistry. Percentages of peripheral blood NK (pNK) and decidual NK (dNK) cells and the levels of intracellular interferon (IFN)-γ, perforin and granzyme B in normal pregnancies, late-onset and early-onset PE were analyzed using flow cytometry. Cytolytic functions of dNK cells from normal and PE pregnancies were examined. Effects of conditioned medium (CM) of dNK cells from normal and PE pregnancies on first trimester trophoblast invasion and migration were tested. In early pregnancy samples (9-13 weeks of gestation), we noted moderate vessel remodeling with abundant perivascular NK cells but a limited number of surrounding EVTs. The numbers of both human pNK cells and dNK cells and intracellular interferon (IFN)-γ, perforin and granzyme B production were significantly higher in PE compared with normal pregnancies at the time of delivery for both early- and late-onset disease. dNK cells from PE pregnancies not only killed first trimester trophoblasts but also inhibited their invasion and migration when compared to normal controls. Our results suggest that NK cells, in conjunction with EVTs, may play an important role in controlling uterine SA remodeling at the early stages of vessel remodeling, but they contribute to the pathogenesis of PE in late pregnancy.
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http://dx.doi.org/10.1080/14767058.2020.1740675DOI Listing
March 2020
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