Publications by authors named "Xueli Zhang"

323 Publications

Discovery of bladder cancer biomarkers in paired pre- and postoperative urine samples.

Transl Androl Urol 2021 Aug;10(8):3402-3414

Department of Urology, The Fifth Medical Centre of Chinese PLA General Hospital, Beijing, China.

Background: Bladder cancer (BC), a common cancer of the urinary system, has a low mortality but an extremely high recurrence rate. Patients who have undergone initial surgical treatment often undergo frequent prognostic examinations with a substantial burden of discomfort and costs. Urine samples can reflect early disease processes in the urinary system and may be an excellent source of biomarkers.

Methods: In the present study, we used the liquid chromatography with tandem mass spectrometry (LC-MS/MS) to perform proteomic analysis of pre- and postoperative urine samples from patients with stage III BC to identify biomarkers of cancer prognosis. Candidate biomarkers from proteomic analysis were simultaneously validated using western blotting in an independent cohort and immunohistochemical (IHC) staining, combined with gene expression data of BC samples in The Cancer Genome Atlas (TCGA).

Results: The comparison of pre- and postoperative urine samples from the same patients led to the discovery of several significantly differentially expressed proteins, whose functions could be closely related to the occurrence and development of BC. We confirmed a representative group of candidate biomarker molecules, such as cadherin-related family member 2 (CDHR2), heat shock protein beta-1 (HSP27), and heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1).

Conclusions: The candidate biomarker molecules can distinguish between pre- and postoperative urine samples, and alterations in their expression levels are significantly associated with recurrence rates in patients with BC. Therefore, these molecules may become useful biomarkers for the monitoring and prognosis of BC.
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http://dx.doi.org/10.21037/tau-21-562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421825PMC
August 2021

Associations of ophthalmic and systemic conditions with incident dementia in the UK Biobank.

Br J Ophthalmol 2021 Sep 13. Epub 2021 Sep 13.

Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, People's Republic of China

Aims: To examine independent and interactive associations of ophthalmic and systemic conditions with incident dementia.

Methods: Our analysis included 12 364 adults aged 55-73 years from the UK Biobank cohort. Participants were assessed between 2006 and 2010 at baseline and were followed up until the early of 2021. Incident dementia was ascertained using hospital inpatient, death records and self-reported data.

Results: Over 1 263 513 person-years of follow-up, 2304 cases of incident dementia were documented. The multivariable-adjusted HRs (95% CI) for dementia associated with age-related macular degeneration (AMD), cataract, diabetes-related eye disease (DRED) and glaucoma at baseline were 1.26 (1.05 to 1.52), 1.11 (1.00 to 1.24), 1.61 (1.30 to 2.00) and (1.07 (0.92 to 1.25), respectively. Diabetes, heart disease, stroke and depression at baseline were all associated with an increased risk of dementia. Of the combination of AMD and a systemic condition, AMD-diabetes was associated with the highest risk for incident dementia (HR (95% CI): 2.73 (1.79 to 4.17)). Individuals with cataract and a systemic condition were 1.19-2.29 times more likely to develop dementia compared with those without cataract and systemic conditions. The corresponding number for DRED and a systemic condition was 1.50-3.24. Diabetes, hypertension, heart disease, depression and stroke newly identified during follow-up mediated the association between cataract and incident dementia as well as the association between DRED and incident dementia.

Conclusions: AMD, cataract and DRED but not glaucoma are associated with an increased risk of dementia. Individuals with both ophthalmic and systemic conditions are at higher risk of dementia compared with those with an ophthalmic or systemic condition only.
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http://dx.doi.org/10.1136/bjophthalmol-2021-319508DOI Listing
September 2021

Occupational injuries and psychological support in Chinese nurses: a cross-sectional study.

Rev Esc Enferm USP 2021 13;55:e20200422. Epub 2021 Sep 13.

Chinese PLA General Hospital, Departament of Epidemiology and Statistics, Graduate School, Beijing, China.

Objective: To assess the occupational injuries and psychological support received by nurses and to investigate the relationship between the two.

Method: This was a nation-wide cross-sectional study of nurses working across 1858 hospitals in China. Data were collected using an online structured, self-administered questionnaire between 2016 and 2017.

Results: Nearly half of respondents had experienced aggressive behavior from patients or their attendants; 13.4% respondents had experienced aggressive behavior on more than three occasions. 78.96% respondents had experienced needle-stick injuries and 51.22% had experienced psychological trauma. 20.5% respondents believed that hospitals do not pay any attention to occupational safety. 86.1% respondents expressed the need for little or moderate psychological support. Nurses who had experienced aggressive behavior expressed a greater need for psychological support. Nurses working at hospitals that adequately addressed the occupational safety issues expressed the lowest need for psychological support.

Conclusion: We found a high prevalence of psychological stress and occupational injuries among nurses. Nursing managers need to address this issue and implement interventions to prevent and reduce injuries.
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http://dx.doi.org/10.1590/1980-220X-REEUSP-2020-0422DOI Listing
September 2021

Multiple strategies for metabolic engineering of Escherichia coli for efficient production of glycolate.

Biotechnol Bioeng 2021 Sep 7. Epub 2021 Sep 7.

Tianjin Institute of Industrial Biotechnology, Chinese of Academy of Sciences, Tianjin, China.

Glycolate is a bulk chemical with wide applications in the textile, food processing, and pharmaceutical industries. Glycolate can be produced from glucose via the glycolysis and glyoxylate shunt pathways, followed by reduction to glycolate. However, two problems limit the productivity and yield of glycolate when using glucose as the sole carbon source. The first is a cofactor imbalance in the production of glycolate from glucose via the glycolysis pathway, since NADPH is required for glycolate production, while glycolysis generates NADH. To rectify this imbalance, the NADP -dependent glyceraldehyde 3-phosphate dehydrogenase GapC from Clostridium acetobutylicum was introduced to generate NADPH instead of NADH in the oxidation of glyceraldehyde 3-phosphate during glycolysis. The soluble transhydrogenase SthA was further eliminated to conserve NADPH by blocking its conversion into NADH. The second problem is an unfavorable carbon flux distribution between the tricarboxylic acid cycle and the glyoxylate shunt. To solve this problem, isocitrate dehydrogenase (ICDH) was eliminated to increase the carbon flux of glyoxylate and thereby improve the glycolate titer. After engineering through the integration of gapC, combined with the inactivation of ICDH, SthA, and by-product pathways, as well as the upregulation of the two key enzymes isocitrate lyase (encoding by aceA), and glyoxylate reductase (encoding by ycdW), the glycolate titer increased to 5.3 g/L with a yield of 1.89 mol/mol glucose. Moreover, an optimized fed-batch fermentation reached a titer of 41 g/L with a yield of 1.87 mol/mol glucose after 60 h.
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http://dx.doi.org/10.1002/bit.27934DOI Listing
September 2021

Visual Impairment and Risk of Dementia: the UK Biobank Study.

Am J Ophthalmol 2021 Aug 22. Epub 2021 Aug 22.

Department of Ophthalmology, Guangdong Academy of Medical Sciences, Guangdong Provincial People's Hospital, Guangzhou, China; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China; Centre for Eye Research, Melbourne University, East Melbourne, Victoria, Australia. Electronic address:

Purpose: The association between visual impairment (VI) and the risk of dementia has been poorly understood. We sought to investigate the VI-dementia relationship in the UK Biobank Study.

Design: Prospective cohort study METHODS: : A total of 117,187 volunteers (aged 40-69 years) deemed free of dementia at baseline were included. Habitual distance visual acuity worse than 0.3 logMAR units in the better-seeing eye was used to define VI. The incident dementia was based on electronically linked hospital inpatient and death records.

Results: During a median follow up of 5.96 years, the presence of VI was significantly associated with incident dementia (HR=1.78, 95% CI: 1.18-2.68, P=0.006). There was a clear trend between the severity of VI and the risk of dementia (P for trend=0.002).

Conclusions: We found VI was associated with increased risk of dementia, with a progressively greater risk among those with worse visual acuity. Our findings suggested that visual impairment might be a modifiable risk factor for dementia and highlighted the potential value of VI elimination to delay the manifestation of dementia.
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http://dx.doi.org/10.1016/j.ajo.2021.08.010DOI Listing
August 2021

Helicase-AID: A novel molecular device for base editing at random genomic loci.

Metab Eng 2021 Sep 17;67:396-402. Epub 2021 Aug 17.

Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China; Key Laboratory of Systems Microbial Biotechnology, Chinese Academy of Sciences, Tianjin, China; National Technology Innovation Center of Synthetic Biology, Tianjin, China. Electronic address:

CRISPR-enabled deaminase base editing has become a powerful tool for precisely editing nucleotides on the chromosome. In this study DNA helicases, such as Escherichia coli DnaB, were fused to activation-induced cytidine deaminase (AID) to form enzyme complexes which randomly introduces edited bases throughout the chromosome. DnaB-AID was found to increase 2.5 × 10 fold relative to the mutagenesis frequency of wildtype. 97.9% of these edits were observed on the leading strand during DNA replication suggesting deamination to be highly coordinated with DNA replication. Using DnaB-AID, a 371.4% increase in β-carotene production was obtained following four rounds of editing. In Saccharomyces cerevisiae Helicase-AID was constructed by fusing AID to one of the subunits of eukaryotic helicase Mcm2-7 complex, MCM5. Using MCM5-AID, the average editing efficiency of five strains was 2.1 ± 0.4 × 10 fold higher than the native genomic mutation rate. MCM5-AID was able to improve β-carotene production of S. cerevisiae 4742crt by 75.4% following eight rounds of editing. The S. cerevisiae MCM5-AID technique is the first biological tool for generating and accumulating single base mutations in eukaryotic chromosomes. Since the helicase complex is highly conservative in all eukaryotes, Helicase-AID could be adapted for various applications and research in all eukaryotic cells.
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http://dx.doi.org/10.1016/j.ymben.2021.08.005DOI Listing
September 2021

Metabolic engineering of microorganisms for L-alanine production.

J Ind Microbiol Biotechnol 2021 Aug 19. Epub 2021 Aug 19.

Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China.

L-alanine is extensively used in chemical, food and medicine industries. Industrial production of L-alanine has been mainly based on the enzymatic process using petroleum-based L-aspartic acid as the substrate. L-alanine production from renewable biomass using microbial fermentation process is an alternative route. Many microorganisms can naturally produce L-alanine using aminotransferase or L-alanine dehydrogenase. However, production of L-alanine using the native strains has been limited due to their low yields and productivities. In this review, metabolic engineering of microorganisms for L-alanine production was summarized. Among them, the Escherichia coli strains developed by Dr. Lonnie Ingram's group which can produce L-alanine with anaerobic fermentation process had several advantages, especially having high L-alanine yield, and it was the first one that realized commercialization. L-alanine is also the first amino acid that could be industrially produced by anaerobic fermentation.
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http://dx.doi.org/10.1093/jimb/kuab057DOI Listing
August 2021

Fine-tuning the expression of pathway gene in yeast using a regulatory library formed by fusing a synthetic minimal promoter with different Kozak variants.

Microb Cell Fact 2021 Jul 28;20(1):148. Epub 2021 Jul 28.

Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, 32 West 7th Avenue, Tianjin Airport Economic Area, Tianjin, 300308, People's Republic of China.

Background: Tailoring gene expression to balance metabolic fluxes is critical for the overproduction of metabolites in yeast hosts, and its implementation requires coordinated regulation at both transcriptional and translational levels. Although synthetic minimal yeast promoters have shown many advantages compared to natural promoters, their transcriptional strength is still limited, which restricts their applications in pathway engineering.

Results: In this work, we sought to expand the application scope of synthetic minimal yeast promoters by enhancing the corresponding translation levels using specific Kozak sequence variants. Firstly, we chose the reported UAS-Core1 minimal promoter as a library template and determined its Kozak motif (K). Next, we randomly mutated the K to generate a chimeric promoter library, which was able to drive green fluorescent protein (GFP) expression with translational strengths spanning a 500-fold range. A total of 14 chimeric promoters showed at least two-fold differences in GFP expression strength compared to the K control. The best one named K even showed 8.5- and 3.3-fold increases in fluorescence intensity compared with UAS-Core1 and the strong native constitutive promoter P, respectively. Subsequently, we chose three representative strong chimeric promoters (K, K, and K) from this library to regulate pathway gene expression. In conjunction with the tHMG1 gene for squalene production, the K variant produced the best squalene titer of 32.1 mg/L in shake flasks, which represents a more than 10-fold increase compared to the parental K control (3.1 mg/L).

Conclusions: All these results demonstrate that this chimeric promoter library developed in this study is an effective tool for pathway engineering in yeast.
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http://dx.doi.org/10.1186/s12934-021-01641-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317321PMC
July 2021

Small intestinal bacterial overgrowth and evaluation of intestinal barrier function in patients with ulcerative colitis.

Am J Transl Res 2021 15;13(6):6605-6610. Epub 2021 Jun 15.

Gastroenterology Department, The First Hospital of Hebei Medical University Shijiazhuang, Hebei, China.

Objective: To investigate the small intestinal bacterial overgrowth (SIBO) and to evaluate the intestinal barrier function in ulcerative colitis (UC) patients treated with mesalazine and rifaximin.

Methods: 96 patients undergoing the methane-hydrogen breath test in our hospital from January 2018 to January 2020 were enrolled in the study group, and 40 healthy persons were enrolled in the control group during this period. The SIBO positive rate of the two groups were collected and compared. Then, the SIBO positive patients were divided into group A and group B. Group A and group B all received mesalazine, and group B received rifaximin plus. The clinical efficacy, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and intestinal barrier function indexes like diamine oxidase (DAO) and D-lactic acid (DLA) were recorded and compared.

Results: The study group presented higher SIBO positive rate compared with the control group (56% vs. 25%, P<0.05). After treatment, group B showed better clinical efficacy and lower levels of ESR and CRP than group A (all P<0.05). After treatment, the DAO and D-LA levels of the two groups were decreased, and presented lower levels in group B than group A (all P<0.05).

Conclusion: UC patients present a higher positive rate in SIBO. Mesalazine and rifaximin are applied to patients with mild to moderate UC, and their clinical efficacy has been significantly enhanced after the eradication of SIBO.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290731PMC
June 2021

Serum Metabolic Profiling of Late-Pregnant Women With Antenatal Depressive Symptoms.

Front Psychiatry 2021 8;12:679451. Epub 2021 Jul 8.

Shanghai Key Laboratory of Forensic Medicine (Academy of Forensic Science), Shanghai, China.

Antenatal depression (AD) is a major public health issue worldwide and lacks objective laboratory-based tests to support its diagnosis. Recently, small metabolic molecules have been found to play a vital role in interpreting the pathogenesis of AD. Thus, non-target metabolomics was conducted in serum. Liquid chromatography-tandem mass spectrometry-based metabolomics platforms were used to conduct serum metabolic profiling of AD and non-antenatal depression (NAD). Orthogonal partial least squares discriminant analysis, the non-parametric Mann-Whitney test, and Benjamini-Hochberg correction were used to identify the differential metabolites between AD and NAD groups; Spearman's correlation between the key differential metabolites and Edinburgh Postnatal Depression Scale (EPDS) and the stepwise logistic regression analysis was used to identify potential biomarkers. In total, 79 significant differential metabolites between AD and NAD were identified. These metabolites mainly influence amino acid metabolism and glycerophospholipid metabolism. Then, PC (16:0/16:0) and betaine were significantly positively correlated with EPDS. The simplified biomarker panel consisting of these three metabolites [betaine, PC (16:0/16:0) and succinic acid] has excellent diagnostic performance (95% confidence interval = 0.911-1.000, specificity = 95%, sensitivity = 85%) in discriminating AD and NAD. The results suggested that betaine, PC (16:0/16:0), and succinic acid were potential biomarker panels, which significantly correlated with depression; and it could make for developing an objective method in future to diagnose AD.
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http://dx.doi.org/10.3389/fpsyt.2021.679451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295540PMC
July 2021

PLEKHO2 inhibits TNFα-induced cell death by suppressing RIPK1 activation.

Cell Death Dis 2021 Jul 16;12(8):714. Epub 2021 Jul 16.

Department of Biomedical Engineering, the Fifth medical Centre, Chinese PLA General Hospital, Beijing, 100071, China.

Receptor interaction protein kinase 1 (RIPK1) plays a diverse role in tumor necrosis factor α (TNFα) signalings. The ubiquitination of RIPK1 is essential for NF-κB activation, whereas its kinase activity promotes apoptosis and necroptosis. However, the mechanisms underlying have not been fully illuminated. Here we report that PH domain-containing family O member 2 (PLEKHO2) inhibits RIPK1-dependent cell death and is necessary for NF-κB activation in response to TNFα. Cells of PLKEHO2 deficiency are more susceptible to TNF-α induced apoptosis and necroptosis with increased RIPK1 activation, which is consistent with the observation that the susceptibility of PLEKHO2-/- cells is effectively prevented by treatment of RIPK1 kinase inhibitor. Moreover, PLEKHO2 deficient cells exhibit compromised RIPK1 ubiquitination and NF-κB activation in response to TNFα. Ultimately, PLEKHO2-deficient mice display greatly increased hepatotoxicity and lethality after TNFα-induced hepatitis. In summary, our study revealed that PLEKHO2 is a novel inhibitor of apoptosis and necroptosis, which plays a key role in regulating RIPK1 ubiquitination and activation.
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http://dx.doi.org/10.1038/s41419-021-04001-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285381PMC
July 2021

Biosynthesis of the Oleanane-Type Triterpenoids of Tunicosaponins in Yeast.

ACS Synth Biol 2021 08 14;10(8):1874-1881. Epub 2021 Jul 14.

School of Chinese Materia Medica and Yunnan Key Laboratory of Southern Medicinal Resource, Yunnan University of Chinese Medicine, Kunming, 650500, China.

Tunicosaponins are natural products extracted from , which is an important ingredient of Yunnan Baiyao Powder, an ancient and famous Asian herbal medicine. The representative aglycones of tunicosaponins are the oleanane-type triterpenoids of gypsogenin and quillaic acid, which were found to manipulate a broad range of virus-host fusion via wrapping the heptad repeat-2 (HR2) domain prevalent in viral envelopes. However, the unknown biosynthetic pathway and difficulty in chemical synthesis hinder the therapeutic use of tunicosaponins. Here, two novel cytochrome P450-dependent monooxygenases that take part in the biosynthesis of tunicosaponins, CYP716A262 (CYP091) and CYP72A567 (CYP099), were identified from . In addition, the whole biosynthesis pathway of the tunicosaponin aglycones was reconstituted in yeast by transforming the platform strain BY-bAS with the CYP716A262 and CYP716A567 genes, the resulting strain could produce 146.84 and 314.01 mg/L of gypsogenin and quillaic acid, respectively. This synthetic biology platform for complicated metabolic pathways elucidation and microbial cell factories construction can provide alternative sources of important natural products, helping conserve natural plant resources.
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http://dx.doi.org/10.1021/acssynbio.1c00065DOI Listing
August 2021

Directed evolution of alditol oxidase for the production of optically pure D-glycerate from glycerol in the engineered Escherichia coli.

J Ind Microbiol Biotechnol 2021 Aug;48(7-8)

Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, 32 Xiqidao, Tianjin Airport Economic Park, Tianjin 300308, China.

D-glycerate is an attractive chemical for a wide variety of pharmaceutical, cosmetic, biodegradable polymers, and other applications. Now several studies have been reported about the synthesis of glycerate by different biotechnological and chemical routes from glycerol or other feedstock. Here, we present the construction of an Escherichia coli engineered strain to produce optically pure D-glycerate by oxidizing glycerol with an evolved variant of alditol oxidase (AldO) from Streptomyces coelicolor. This is achieved by starting from a previously reported variant mAldO and employing three rounds of directed evolution, as well as the combination of growth-coupled high throughput selection with colorimetric screening. The variant eAldO3-24 displays a higher substrate affinity toward glycerol with 5.23-fold than the wild-type AldO, and a 1.85-fold increase of catalytic efficiency (kcat/KM). Then we introduced an isopropyl-β-D-thiogalactopyranoside (IPTG)-inducible T7 expression system in E. coli to overexpress the variant eAldO3-24, and deleted glucosylglycerate phosphorylase encoding gene ycjM to block the consumption of D-glycerate. Finally, the resulting strain TZ-170 produced 30.1 g/l D-glycerate at 70 h with a yield of 0.376 mol/mol in 5-l fed-batch fermentation.
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http://dx.doi.org/10.1093/jimb/kuab041DOI Listing
August 2021

Engineering yeast subcellular compartments for increased production of the lipophilic natural products ginsenosides.

Metab Eng 2021 Sep 18;67:104-111. Epub 2021 Jun 18.

Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, China; National Technology Innovation Center of Synthetic Biology, China. Electronic address:

Eukaryotic yeasts have a variety of subcellular compartments and are ideal platform strains for the construction of complex heterologous natural product biosynthesis pathways. Improving the synthesis efficiency of microbial cell factories through the utilization and modification of subcellular compartments by synthetic biology has good application prospects. Here, we used the yeast PLN1 protein to target the normally endoplasmic reticulum (ER)-localized cytochrome P450 enzyme protopanaxadiol (PPD) synthase (PPDS) to lipid droplets (LDs), which are the storage organelles of the PPDS substrate dammarenediol-II (DD). The efficiency of converting DD to PPD was significantly increased by 394%, and the conversion rate of DD increased from 17.4% to 86.0%. Furthermore, increasing the volume of LDs can significantly enhance the production of DD and its derivatives, but the change in the ratio of the volume and surface area of LDs decreased the conversion efficiency of DD to PPD. Additionally, the biosynthetic pathways of the PPD-type saponin ginsenoside compound K (CK) was reconstituted in a PPD-producing chassis strain, and CK production reached 21.8 mg/L/OD, 4.4-fold higher compared to the native ER-expression strategy. Next, we enhanced the expression of the Pn3-29 gene module to further reduce the accumulation of PPD and increase the production of CK to 41.3 mg/L/OD. Finally, the CK titer of the resulting strain reached 5 g/L in 5 L fed-batch fermentations. This study provides a new strategy for engineering yeast to produce complex natural products.
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http://dx.doi.org/10.1016/j.ymben.2021.06.002DOI Listing
September 2021

CircASXL1 knockdown represses the progression of colorectal cancer by downregulating GRIK3 expression by sponging miR-1205.

World J Surg Oncol 2021 Jun 14;19(1):176. Epub 2021 Jun 14.

Department of General Surgery, Shanghai Fengxian Central Hospital, No. 6600, Nanfeng Road, Nanqiao New Town, Fengxian District, Shanghai, 201400, China.

Background: Colorectal cancer (CRC) is a common aggressive tumor that poses a heavy burden to human health. An increasing number of studies have reported that circular RNA (circRNA) is involved in the progression of CRC. In this study, the special profiles of circASXL1 (circ_0001136) in CRC progression were revealed.

Methods: The expression of circASXL1, microRNA-1205 (miR-1205), and glutamate ionotropic receptor kainate type subunit 3 (GRIK3) mRNA was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression was determined by Western blot or immunohistochemistry. Cell colony-forming ability was investigated by colony formation assay. Cell cycle and apoptosis were demonstrated using cell-cycle and cell-apoptosis analysis assays, respectively. Cell migration and invasion were detected by wound-healing and transwell migration and invasion assays, respectively. The binding sites between miR-1205 and circASXL1 or GRIK3 were predicted by circBank or miRDB online database, and identified by dual-luciferase reporter assay. The impact of circASXL1 on tumor formation in vivo was investigated by in vivo tumor formation assay.

Results: CircASXL1 and GRIK3 expression were apparently upregulated, and miR-1205 expression was downregulated in CRC tissues and cells relative to control groups. CircASXL1 knockdown inhibited cell colony-forming ability, migration and invasion, whereas induced cell arrest at G0/G1 phase and cell apoptosis in CRC cells; however, these effects were attenuated by miR-1205 inhibitor. Additionally, circASXL1 acted as a sponge for miR-1205, and miR-1205 was associated with GRIK3. Furthermore, circASXL1 silencing hindered tumor formation by upregulating miR-1205 and downregulating GRIK3 expression.

Conclusion: CircASXL1 acted an oncogenic role in CRC malignant progression via inducing GRIK3 through sponging miR-1205. Our findings provide a theoretical basis for studying circASXL1-directed therapy for CRC.
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http://dx.doi.org/10.1186/s12957-021-02275-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204566PMC
June 2021

[Construction of Escherichia coli cell factories].

Sheng Wu Gong Cheng Xue Bao 2021 May;37(5):1564-1577

Tianjin Institute of Industrial Biotechnology, Chinese Academy of Science, Tianjin 300308, China.

As an important model industrial microorganism, Escherichia coli has been widely used in pharmaceutical, chemical industry and agriculture. In the past 30 years, a variety of new strategies and techniques, including artificial intelligence, gene editing, metabolic pathway assembly, and dynamic regulation have been used to design, construct, and optimize E. coli cell factories, which remarkably improved the efficiency for biotechnological production of chemicals. In this review, three key aspects for constructing E. coli cell factories, including pathway design, pathway assembly and regulation, and optimization of global cellular performance, are summarized. The technologies that have played important roles in metabolic engineering of E. coli, as well as their future applications, are discussed.
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http://dx.doi.org/10.13345/j.cjb.200716DOI Listing
May 2021

[Validity of the international physical activity questionnaire and bouchard diary in Chinese adults].

Wei Sheng Yan Jiu 2021 May;50(3):435-441

National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China.

Objective: Based on the accelerometer, the validity of the international physical activity questionnaire long version(IPAQ-L) and Bouchard diary were evaluated to measure the daily physical activity of Chinese adults aged 18-59 years old.

Methods: A total of 200 Chinese adults were recruited in Yinzhou District of Ningbo City in 2019, including 78 males and 122 females, the three age groups 18-29, 30-49, 50 and above accounted for 19. 5%, 61. 5% and 18. 0%, respectively. The volunteers wore Actigraph WGT3 x-BT three-dimensional accelerometer for 3 days, and completed the 3 consecutive days& apos; Bouchard diary and the IPAQ-L. The physical activity energy expenditure(PAEE), sedentary inactivity time, light physical activity time(LPA) and moderate-to-vigorous physical activity time(MVPA) measured by the three tools were estimated respectively. Spearman analysis was used to analyze the correlation, the Friedman test and the Bland-Altman plot were used to test the homogeneity of the three method.

Results: 196 volunteers were included in this study. The correlation coefficients of PAEE between IPAQ and diary and accelerometer were 0. 32 and 0. 58, respectively, the correlation coefficients of sedentary behavior were 0. 17, 0. 25, and LPA time was 0. 33, and the estimated IPAQ for MVPA time better than diary. The difference test result showed that, except for IPAQ in the measurement of MVPA, there was no statistical difference from the accelerometer measurement result(P=0. 684), and the difference between other estimated values and the accelerometer measurement result was statistically significant(P& lt; 0. 01), Bland-Altman plot result showed that the diary and IPAQ had good consistency in the measurement of PAEE and IPAQ in the estimation of MVPA time, but there was an overestimation in PAEE. In addition, IPAQ had poor validity in measuring sedentary behavior and LPA.

Conclusion: IPAQ and Bouchard diary have better validity in evaluating PAEE, and the diary is better than IPAQ. IPAQ has better validity in evaluating MVPA time, but has poor validity in estimating sedentary behavior and LPA time.
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http://dx.doi.org/10.19813/j.cnki.weishengyanjiu.2021.03.015DOI Listing
May 2021

Improving the bioavailability and bioactivity of garlic bioactive compounds nanotechnology.

Crit Rev Food Sci Nutr 2021 Jun 1:1-30. Epub 2021 Jun 1.

Key Laboratory of Food Processing Technology and Quality Control in Shandong Province, College of Food Science and Engineering, Shandong Agricultural University, Tai'an, China.

This review highlights main bioactive compounds and important biological functions especially anticancer effects of the garlic. In addition, we review current literature on the stability and bioavailability of garlic components. Finally, this review aims to provide a potential strategy for using nanotechnology to increase the stability and solubility of garlic components, providing guidelines for the qualities of garlic products to improve their absorption and prevent their early degradation, and extend their circulation time in the body. The application of nanotechnology to improve the bioavailability and targeting of garlic compounds are expected to provide a theoretical basis for the functional components of garlic to treat human health. We review the improvement of bioavailability and bioactivity of garlic bioactive compounds via nanotechnology, which could promisingly overcome the limitations of conventional garlic products, and would be used to prevent and treat cancer and other diseases in the near future.
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http://dx.doi.org/10.1080/10408398.2021.1929058DOI Listing
June 2021

TNPO1-mediated nuclear import of ARID1B promotes tumor growth in ARID1A-deficient gynecologic cancer.

Cancer Lett 2021 Sep 25;515:14-27. Epub 2021 May 25.

Department of Obstetrics and Gynecology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, PR China. Electronic address:

Karyopherin-β proteins are critically involved in cancer progression and have been reported as potential biomarkers and therapeutic targets for tumor treatment. However, TNPO1, as an important karyopherin-β family member, underlying functional roles in cancers remain largely unclear. In this study, under integrated gene-expression profiling screen of karyopherin-β in gynecologic cancer, we identify TNPO1 as a pivotal contributor to the gynecologic cancer progression. Remarkably, ARID1A-deficient gynecologic cancer cells are specifically vulnerable to the genetic perturbations of TNPO1 in vitro and in vivo. Mechanistically, TNPO1 is selectively responsible for nuclear import of ARID1B, which is a synthetic lethal target in ARID1A-inactivating mutation cancers. Furthermore, TNPO1 or ARID1B knockdown changes chromatin accessibility that results in loss of H3K4me1 and H3K27ac marker, diminishing activated transcription factor of the AP-1 family, and inactivating the PI3K/AKT signaling pathway by reducing growth pathway genes expression including PIK3CA and FGFR2. Together, this work indicates that the oncogenic function of TNPO1 and maybe represent a novel therapeutic strategy to treat ARID1A-deficient gynecologic cancer.
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http://dx.doi.org/10.1016/j.canlet.2021.05.016DOI Listing
September 2021

Rapamycin protects against aristolochic acid nephropathy in mice by potentiating mammalian target of rapamycin‑mediated autophagy.

Mol Med Rep 2021 07 6;24(1). Epub 2021 May 6.

Department of Nephrology, Qilu Hospital, Shandong University, Jinan, Shandong 250015, P.R. China.

Autophagy serves a crucial role in the etiology of kidney diseases, including drug‑induced renal impairment, inherited kidney disease, diabetic nephropathy and aristolochic acid nephropathy (AAN) and is, therefore, a potential target for treatment. We previously demonstrated that rapamycin could attenuate AAN in mice; however, the underlying mechanism remains to be elucidated. Therefore, whether the renal protective effect of rapamycin (an autophagy activator) is related to autophagy in aristolochic acid (AA)‑treated mice was of particular interest. The pathophysiological roles of rapamycin were investigated in AA‑induced nephrotoxicity in mice and the mechanisms of rapamycin action were explored by evaluating the modulation of autophagy in rapamycin‑treated mice and cultured renal tubular epithelial cells. Supplementation with rapamycin reversed AA‑induced kidney injury in mice and improved AA‑induced autophagy damage and . Mechanistically, rapamycin inhibited the renal expression of phosphorylated (p‑)mammalian target of rapamycin (mTOR) and p‑ribosomal S6 protein kinase 1, which in turn activated renal autophagy and decreased apoptosis, probably by removing AA‑elicited damaged mitochondria and misfolded proteins. The findings of the present study demonstrated that rapamycin protects against AA‑induced nephropathy by activating the mTOR‑autophagy axis and suggested that rapamycin may be a promising pharmacological target for the treatment of AAN.
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http://dx.doi.org/10.3892/mmr.2021.12134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127069PMC
July 2021

Water Use by Chinese Pine Is Less Conservative but More Closely Regulated Than in Mongolian Scots Pine in a Plantation Forest, on Sandy Soil, in a Semi-Arid Climate.

Front Plant Sci 2021 9;12:635022. Epub 2021 Apr 9.

Institute of Desertification Studies, Chinese Academy of Forestry, Beijing, China.

The diversity of plant water use patterns among species and ecosystems is a matter of widespread debate. In this study, Chinese pine (, ) and Mongolian Scots pine ( var. , ), which is co-exist in the shelterbelt plantations in the Horqin Sandyland in northern China, were chosen for comparison of water use traits by monitoring xylem sap flow alongside recordings of the associated environmental factors over four growing seasons. Continuous sap flux density measurements were converted into crown projected area transpiration intensity (T) and canopy stomatal conductance (G). The results indicated that showed a higher canopy transpiration intensity than in , with T daily means (±standard deviation) of 0.84 ± 0.36 and 0.79 ± 0.43 mm⋅d, respectively ( = 0.07). However, the inter-annual variability of daily T in was not significant, varying only approximately a 1.1-fold ( = 0.29), while inter-annual variation was significant for , with 1.24-fold variation ( < 0.01). In particular, the daily mean T value for was approximately 1.7-times higher than that of under favorable soil moisture conditions, with values for relative extractable soil water within the 0-1.0 m soil layer (REW) being above 0.4. However, as the soil dried out, the value of T for decreased more sharply, falling to only approximately 0.5-times the value for when REW fell to < 0.2. The stronger sensitivity of T and/or G to REW, together with the more sensitive response of G to VPD in , confirms that exhibits less conservation of soil water utilization but features a stronger ability to regulate water use. Compared with , can better adapt to the dry conditions associated with climate change.
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http://dx.doi.org/10.3389/fpls.2021.635022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062886PMC
April 2021

Responsive optical probes for deep-tissue imaging: Photoacoustics and second near-infrared fluorescence.

Adv Drug Deliv Rev 2021 06 25;173:141-163. Epub 2021 Mar 25.

School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address:

Optical imaging has played a vital role in development of biomedicine and image-guided theragnostic. Nevertheless, the clinical translation of optical molecular imaging for deep-tissue visualization is still limited by poor signal-to-background ratio and low penetration depth owing to light scattering and tissue autofluorescence. Hence, to facilitate precise diagnosis and accurate surgery excision in clinical practices, the responsive optical probes (ROPs) are broadly designed for specific reaction with biological analytes or disease biomarkers via chemical/physical interactions for photoacoustic and second near-infrared fluorescence (NIR-II, 900-1700 nm) fluorescence imaging. Herein, the recent advances in the development of ROPs including molecular design principles, activated mechanisms and treatment responses for photoacoustic and NIR-II fluorescence imaging are reviewed. Furthermore, the present challenges and future perspectives of ROPs for deep-tissue imaging are also discussed.
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http://dx.doi.org/10.1016/j.addr.2021.03.008DOI Listing
June 2021

Home sleep apnea testing of adults with chronic heart failure.

J Clin Sleep Med 2021 07;17(7):1453-1463

Department of Medicine and Center for Sleep and Circadian Neurobiology, University of Pennsylvania, Philadelphia, Pennsylvania.

Study Objectives: To evaluate home sleep apnea testing (HSAT) using a type 3 portable monitor to help diagnose sleep-disordered breathing (SDB) and identify respiratory events including obstructive sleep apnea, central sleep apnea, and Cheyne-Stokes respiration in adults with stable chronic heart failure.

Methods: Eighty-four adults with chronic heart failure (86.9% males, age [mean ± standard deviation] 58.7 ± 16.3 years, body mass index 29.4 ± 13.0 kg/m², left ventricular ejection fraction 40.3% ± 11.5%) performed unattended HSAT followed by an in-laboratory polysomnography (PSG) with simultaneous portable monitor recording.

Results: The apnea-hypopnea index was 22.0 ± 17.0 events/h according to HSAT, 26.8 ± 20.5 events/h on an in-laboratory portable monitor, and 23.8 ± 21.3 events/h using PSG (P = .373). A Bland-Altman analysis of the apnea-hypopnea index using HSAT vs PSG showed a mean difference (95% confidence interval) of -2.4 (-4.9 to 0.1) events/h and limits of agreement (±2 standard deviations) of -24.1 to 19.2 events/h. HSAT underestimated the apnea-hypopnea index to a greater extent at a higher apnea-hypopnea index (rho = -.358; P < .001). Similar levels of agreement from HSAT vs PSG were observed when comparing the obstructive apnea index, central apnea index, and percentage of time in a Cheyne-Stokes respiration pattern. When we used an apnea-hypopnea index ≥ 5 events/h to diagnose SDB, HSAT had 86.7% sensitivity, 76.5% specificity, 92.9% positive predictive value, and 61.9% negative predictive value compared to PSG. Detection of Cheyne-Stokes respiration using HSAT showed 94.6% sensitivity, 91.1% specificity, 88.6% positive predictive value, and 97.6% negative predictive value compared to PSG.

Conclusions: HSAT with a type 3 portable monitor can help diagnose SDB and identify obstructive sleep apnea, central sleep apnea, and Cheyne-Stokes respiration events in adults with chronic heart failure.
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http://dx.doi.org/10.5664/jcsm.9224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314621PMC
July 2021

Very-High-Cycle Fatigue Behavior of Inconel 718 Alloy Fabricated by Selective Laser Melting at Elevated Temperature.

Materials (Basel) 2021 Feb 20;14(4). Epub 2021 Feb 20.

School of Aeronautics and Astronautics, Tianjin Sino-German University of Applied Sciences, Tianjin 300350, China.

This study investigates the very-high-cycle fatigue (VHCF) behavior at elevated temperature (650 °C) of the Inconel 718 alloy fabricated by selective laser melting (SLM). The results are compared with those of the wrought alloy. Large columnar grain with a cellular structure in the grain interior and Laves/δ phases precipitated along the grain boundaries were exhibited in the SLM alloy, while fine equiaxed grains were present in the wrought alloy. The elevated temperature had a minor effect on the fatigue resistance in the regime below 10 cycles for the SLM alloy but significantly reduced the fatigue strength in the VHCF regime above 10 cycles. Both the SLM and wrought specimens exhibited similar fatigue resistance in the fatigue life regime of fewer than 10-10 cycles at elevated temperature, and the surface initiation mechanism was dominant in both alloys. In a VHCF regime above 10-10 cycles at elevated temperature, the wrought material exhibited slightly better fatigue resistance than the SLM alloy. All fatigue cracks are initiated from the internal defects or the microstructure discontinuities. The precipitation of Laves and δ phases is examined after fatigue tests at high temperatures, and the effect of microstructure on the formation and the propagation of the microstructural small cracks is also discussed.
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http://dx.doi.org/10.3390/ma14041001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924031PMC
February 2021

RNA tape sampling in cutaneous lupus erythematosus discriminates affected from unaffected and healthy volunteer skin.

Lupus Sci Med 2021 03;8(1)

Biogen Inc, Cambridge, Massachusetts, USA

Objective: Punch biopsy, a standard diagnostic procedure for patients with cutaneous lupus erythematosus (CLE) carries an infection risk, is invasive, uncomfortable and potentially scarring, and impedes patient recruitment in clinical trials. Non-invasive tape sampling is an alternative that could enable serial evaluation of specific lesions. This cross-sectional pilot research study evaluated the use of a non-invasive adhesive tape device to collect messenger RNA (mRNA) from the skin surface of participants with CLE and healthy volunteers (HVs) and investigated its feasibility to detect biologically meaningful differences between samples collected from participants with CLE and samples from HVs.

Methods: Affected and unaffected skin tape samples and simultaneous punch biopsies were collected from 10 participants with CLE. Unaffected skin tape and punch biopsies were collected from 10 HVs. Paired samples were tested using quantitative PCR for a candidate immune gene panel and semi-quantitative immunohistochemistry for hallmark CLE proteins.

Results: mRNA collected using the tape device was of sufficient quality for amplification of 94 candidate immune genes. Among these, we found an interferon (IFN)-dominant gene cluster that differentiated CLE-affected from HV (23-fold change; p<0.001) and CLE-unaffected skin (sevenfold change; p=0.002), respectively. We found a CLE-associated gene cluster that differentiated CLE-affected from HV (fourfold change; p=0.005) and CLE-unaffected skin (fourfold change; p=0.012), respectively. Spearman's correlation between per cent area myxovirus 1 protein immunoreactivity and IFN-dominant mRNA gene cluster expression was highly significant (dermis, rho=0.86, p<0.001). In total, skin tape-derived RNA expression comprising both IFN-dominant and CLE-associated gene clusters correlated with per cent area immunoreactivity of some hallmark CLE-associated proteins in punch biopsies from the same lesions.

Conclusions: A non-invasive tape RNA collection technique is a potential tool for repeated skin biomarker measures throughout a clinical trial.
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http://dx.doi.org/10.1136/lupus-2020-000428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931768PMC
March 2021

Characterization of JEN family carboxylate transporters from the acid-tolerant yeast Pichia kudriavzevii and their applications in succinic acid production.

Microb Biotechnol 2021 05 25;14(3):1130-1147. Epub 2021 Feb 25.

Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, 32 West 7th Ave, Tianjin Airport Economic Park, Tianjin, 300308, China.

The unconventional yeast Pichia kudriavzevii is renowned for its ability to survive at low pH and has been exploited for the industrial production of various organic acids, especially succinic acid (SA). However, P. kudriavzevii can also utilize the di- and tricarboxylate intermediates of the Krebs cycle as the sole carbon sources for cell growth, which may adversely affect the extracellular accumulation of SA. Because the carboxylic acid transport machinery of P. kudriavzevii remains poorly understood, here, we focused on studying its SA transportation process from the perspective of mining and characterization of dicarboxylate transporters in a newly isolated acid-tolerant P. kudriavzevii strain CY902. Through genome sequencing and transcriptome analysis, two JEN family carboxylate transporters (PkJEN2-1 and PkJEN2-2) were found to be involved in SA transport. Substrate specificity analysis revealed that both PkJEN proteins are active dicarboxylate transporters, that can effectively import succinate, fumarate and L-malate into the cell. In addition, PkJEN2-1 can transport α-ketoglutarate, while PkJEN2-2 cannot. Since PkJEN2-1 shows higher transcript abundance than PkJEN2-2, its role in dicarboxylate transport is more important than PkJEN2-2. In addition, PKJEN2-2 is also responsible for the uptake of citrate. To our best knowledge, this is the first study to show that a JEN2 subfamily transporter is involved in tricarboxylate transport in yeast. A combination of model-based structure analysis and rational mutagenesis further proved that amino acid residues 392-403 of the tenth transmembrane span (TMS-X) of PkJEN2-2 play an important role in determining the specificity of the tricarboxylate substrate. Moreover, these two PkJEN transporters only exhibited inward transport activity for SA, and simultaneous inactivation of both PkJEN transporters reduced the SA influx, resulting in enhanced extracellular accumulation of SA in the late stage of fermentation. This work provides useful information on the mechanism of di-/tricarboxylic acid utilization in P. kudriavzevii, which will help improve the organic acid production performance of this microbial chassis.
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http://dx.doi.org/10.1111/1751-7915.13781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085920PMC
May 2021

Protocol for a gallbladder cancer registry study in China: the Chinese Research Group of Gallbladder Cancer (CRGGC) study.

BMJ Open 2021 02 16;11(2):e038634. Epub 2021 Feb 16.

Department of HPB Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.

Introduction: Gallbladder cancer (GBC), the sixth most common gastrointestinal tract cancer, poses a significant disease burden in China. However, no national representative data are available on the clinical characteristics, treatment and prognosis of GBC in the Chinese population.

Methods And Analysis: The Chinese Research Group of Gallbladder Cancer (CRGGC) study is a multicentre retrospective registry cohort study. Clinically diagnosed patient with GBC will be identified from 1 January 2008 to December, 2019, by reviewing the electronic medical records from 76 tertiary and secondary hospitals across 28 provinces in China. Patients with pathological and radiological diagnoses of malignancy, including cancer in situ, from the gallbladder and cystic duct are eligible, according to the National Comprehensive Cancer Network 2019 guidelines. Patients will be excluded if GBC is the secondary diagnosis in the discharge summary. The demographic characteristics, medical history, physical examination results, surgery information, pathological data, laboratory examination results and radiology reports will be collected in a standardised case report form. By May 2021, approximately 6000 patient with GBC will be included. The clinical follow-up data will be updated until 5 years after the last admission for GBC of each patient. The study aimed (1) to depict the clinical characteristics, including demographics, pathology, treatment and prognosis of patient with GBC in China; (2) to evaluate the adherence to clinical guidelines of GBC and (3) to improve clinical practice for diagnosing and treating GBC and provide references for policy-makers.

Ethics And Dissemination: The protocol of the CRGGC has been approved by the Committee for Ethics of Xinhua Hospital, Shanghai Jiao Tong University School of Medicine (SHEC-C-2019-085). All results of this study will be published in peer-reviewed journals and presented at relevant conferences.

Trial Registration Number: NCT04140552, Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2020-038634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888310PMC
February 2021

Screening for obstructive sleep apnea using a contact-free system compared with polysomnography.

J Clin Sleep Med 2021 05;17(5):1075-1082

Department of Pulmonary and Critical Care Medicine, Peking University People's Hospital, Beijing, China.

Study Objectives: To evaluate the utility of a contact-free device in screening for obstructive sleep apnea.

Methods: Three hundred fifty-nine participants (mean age 46 ± 13 years, body mass index 26.1 ± 4.2 kg/m², 67.7% male) underwent overnight monitoring using a contact-free device, the OrbSense, and polysomnography (PSG) in the sleep laboratory simultaneously. The OrbSense recordings were analyzed automatically, and PSG was scored based on recommended guidelines.

Results: The respiratory event index from the OrbSense was lower than the apnea-hypopnea index (AHI) from PSG (25.5 ± 20.7 vs 27.0 ± 25.2 events/h; P = .007) and was significantly correlated with AHI (Pearson coefficient, 0.92; P < .0001). Bland-Altman analysis showed a mean difference of 1.5 events/h, and the limit of agreement was -18.6 to 21.5 events/h. Use of the OrbSense resulted in larger underestimates of AHI and lower negative predictive values at higher AHI values (especially when AHI ≥ 30 events/h). When we used a PSG diagnostic criterion of AHI > 5 events/h, the optimal diagnostic cutoff value from the OrbSense was 8 events/h, with a sensitivity of 90.4%, a specificity of 77.6%, a 94.6% positive predictive value, and a 65% negative predictive value. For patients with moderate to severe obstructive sleep apnea whose AHI was > 15 events/h, the OrbSense cutoff was 16.6 events/h, with a sensitivity of 87.1% and a specificity of 89.7%. Among the 359 participants, 250 patients (69.6%) had the same obstructive sleep apnea severity division classified by both PSG and the OrbSense.

Conclusions: The contact-free device OrbSense can detect respiratory events during sleep and has close agreement with in-laboratory PSG in screening for obstructive sleep apnea. Further studies are warranted to test its utility in community-based settings and at home.
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http://dx.doi.org/10.5664/jcsm.9138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320500PMC
May 2021

The origin and evolution of the diosgenin biosynthetic pathway in yam.

Plant Commun 2021 Jan 2;2(1):100079. Epub 2020 Jun 2.

Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China.

Diosgenin, mainly produced by species, is a traditional precursor of most hormonal drugs in the pharmaceutical industry. The mechanisms that underlie the origin and evolution of diosgenin biosynthesis in plants remain unclear. After sequencing the whole genome of , we revealed the evolutionary trajectory of the diosgenin biosynthetic pathway in and demonstrated the biosynthesis of diosgenin in a yeast cell factory. First, we found that P450 gene duplication and neo-functionalization, driven by positive selection, played important roles in the origin of the diosgenin biosynthetic pathway. Subsequently, we found that the enrichment of diosgenin in the yam lineage was regulated by CpG islands, which evolved to regulate gene expression in the diosgenin pathway and balance the carbon flux between the biosynthesis of diosgenin and starch. Finally, by integrating genes from plants, animals, and yeast, we heterologously synthesized diosgenin to 10 mg/l in genetically-engineered yeast. Our study not only reveals the origin and evolutionary mechanisms of the diosgenin biosynthetic pathway in , but also introduces an alternative approach for the production of diosgenin through synthetic biology.
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http://dx.doi.org/10.1016/j.xplc.2020.100079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816074PMC
January 2021

Effects of effort-reward imbalance, job satisfaction, and work engagement on self-rated health among healthcare workers.

BMC Public Health 2021 01 22;21(1):195. Epub 2021 Jan 22.

Department of Health Related Social and Behavioral Science, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.

Background: Healthcare workers, who protect and improve the health of individuals, are critical to the success of health systems and achieving national and global health goals. To respond effectively to the healthcare needs of populations, healthcare workers themselves must be in a good state of health. However, healthcare workers face various psychosocial pressures, including having to work night shifts, long working hours, demands of patient care, medical disputes, workplace violence, and emotional distress due to poor interactions with patients and colleagues, and poor promotion prospects. Constant exposure to these psychosocial hazards adversely impacts healthcare workers' health. Consequently, this study aimed to examine the influence of effort-reward imbalance, job satisfaction, and work engagement on self-rated health of healthcare workers. The results would be conducive to providing policy guidance to improve the health of healthcare workers.

Methods: We analysed the data of 1327 participants from The Chinese Sixth National Health and Services Survey in Sichuan Province that was conducted from August 2018 to October 2018. Structural equation modelling was used to test the hypothesized relationships among the variables.

Results: Only 40.1% of healthcare workers rated their health as 'relatively good' or 'good'. Effort-reward imbalance had a significant negative correlation with self-rated health (β = - 0.053, 95% CI [- 0.163, - 0.001]). The associations of effort-reward imbalance and work engagement with self-rated health were both mediated by job satisfaction (95% CI [- 0.150, - 0.050] and [0.011, 0.022]), and work engagement mediated the relationship between effort-reward imbalance and self-rated health (95% CI [- 0.064, - 0.008]).

Conclusion: In order to improve the health of healthcare workers, administrators should balance effort and reward and provide opportunities for career development and training. In addition, health managers should help healthcare workers realize the significance and value of their work and keep them actively devoted to their work through incentive mechanisms.
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http://dx.doi.org/10.1186/s12889-021-10233-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821543PMC
January 2021
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