Publications by authors named "Yi Zheng"

1,851 Publications

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Single-cell RNA-sequencing analysis and characterisation of testicular cells in giant panda (Ailuropoda melanoleuca).

Reprod Fertil Dev 2022 Aug 12. Epub 2022 Aug 12.

Context: The giant panda (Ailuropoda melanoleuca) is a rare and endangered species to be preserved in China. The giant panda has a low reproductive capacity, and due to the scarcity of samples, studies on testes from giant panda are very limited, with little knowledge about the process of spermatogenesis in this species.

Aims: To establish the gene expression profiles in cells from the testis of a giant panda.

Methods: The 10×Genomics single-cell RNA-sequencing platform was applied to cells from the testis of an adult giant panda.

Key Results: We identified eight testicular cell types including six somatic and two germ cell types from our single-cell RNA-sequencing datasets. We also identified the differentially expressed genes (DEGs) in each cell type, and performed functional enrichment analysis for the identified testicular cell types. Furthermore, by immunohistochemistry we explored the protein localisation patterns of several marker genes in testes from giant panda.

Conclusions: Our study has for the first time established the gene expression profiles in cells from the testis of a giant panda.

Implications: Our data provide a reference catalogue for spermatogenesis and testicular cells in the giant panda, laying the foundation for future breeding and preservation of this endangered species.
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http://dx.doi.org/10.1071/RD22039DOI Listing
August 2022

DNP and ATP modulate the developments of pulp softening and breakdown in Phomopsis longanae Chi-infected fresh longan through regulating the cell wall polysaccharides metabolism.

Food Chem 2022 Aug 1;397:133837. Epub 2022 Aug 1.

Institute of Postharvest Technology of Agricultural Products, College of Food Science, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, China; Key Laboratory of Postharvest Biology of Subtropical Special Agricultural Products, Fujian Province University, Fuzhou, Fujian 350002, China. Electronic address:

Compared with P. longanae-infected longan, 2, 4-dinitrophenol (DNP) treatment for P. longanae-infected longan displayed the lower levels of pulp firmness, cell wall materials, ionic-soluble pectin, covalent-soluble pectin, hemicellulose, or cellulose, but the higher amount of water-soluble pectin, the higher activities of cell wall-degrading enzymes (CWDEs) (PG, β-Gal, PME, Cx, and XET), and the higher transcript levels of CWDEs-related genes (DlPG1, DlPG2, Dlβ-Gal1, DlPME1, DlPME2, DlPME3, DlCx1, and DlXET30). On the contrary, ATP treatment for P. longanae-infected longan exhibited opposite effects. The above results imply that DNP accelerated P. longanae-induced pulp softening and breakdown of fresh longan, which was because DNP up-regulated the transcript levels of CWDEs-related genes, enhanced the CWDEs activities, and accelerated the degradation of cell wall polysaccharides (CWP). However, ATP suppressed longan pulp softening and breakdown caused by P. longanae, because ATP down-regulated the transcript levels of CWDEs-related genes, lowered the CWDEs activities, and reduced the CWP degradation.
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http://dx.doi.org/10.1016/j.foodchem.2022.133837DOI Listing
August 2022

Single-cell multiomics sequencing reveals the reprogramming defects in embryos generated by round spermatid injection.

Sci Adv 2022 Aug 10;8(32):eabm3976. Epub 2022 Aug 10.

State Key Laboratory of Organ Failure Research, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, P. R. China.

Round spermatid injection (ROSI) technique holds great promise for clinical treatment of a proportion of infertile men. However, the compromised developmental potential of ROSI embryos largely limits the clinical application, and the mechanisms are not fully understood. Here, we describe the transcriptome, chromatin accessibility, and DNA methylation landscapes of mouse ROSI embryos derived from early-stage round spermatids using a single-cell multiomics sequencing approach. By interrogating these data, we identify the reprogramming defects in ROSI embryos at the pronuclear stages, which are mainly associated with the misexpression of a cohort of minor zygotic genome activation genes. We screen a small compound, A366, that can significantly increase the developmental potential of ROSI embryos, in which A366 can partially overcome the reprogramming defects by amending the epigenetic and transcriptomic states. Collectively, our study uncovers the reprogramming defects in ROSI embryos for understanding the mechanisms underlying compromised developmental potential and offers an avenue for ROSI technique optimization.
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http://dx.doi.org/10.1126/sciadv.abm3976DOI Listing
August 2022

A new biomarker for the early diagnosis of gastric cancer: gastric juice- and serum-derived SNCG.

Future Oncol 2022 Aug 10. Epub 2022 Aug 10.

Precision Clinical Laboratory, Central People's Hospital of Zhanjiang, Zhanjiang, Guangdong, China.

To explore the possibility of gastric juice (GJ)- and serum-derived SNCG as a potential biomarker for the early diagnosis of gastric cancer (GC). GJ and serum samples were collected from 87 patients with GC, 38 patients with gastric precancerous lesions and 44 healthy volunteers. The levels of SNCG in GJ and serum samples were detected by ELISA. The levels of SNCG in GJ and serum were significantly higher in the GC group when compared with the GPL group or the control group. The expression of SNCG in GJ and serum was associated with tumor node metastasis stage, lymph node metastasis, tumor size and drinking, and it is important for the diagnosis and prognosis of GC (p < 0.05). The findings highlight the significance of SNCG in GC diagnosis and prognosis and implicate SNCG as a promising candidate for GC treatment.
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http://dx.doi.org/10.2217/fon-2022-0253DOI Listing
August 2022

The spike receptor-binding motif G496S substitution determines the replication fitness of SARS-CoV-2 Omicron sublineage.

Emerg Microbes Infect 2022 Aug 9:1-20. Epub 2022 Aug 9.

State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.

The replication and pathogenicity of SARS-CoV-2 Omicron BA.2 is comparable to that of BA.1 in experimental animal models. However, BA.2 has rapidly emerged to overtake BA.1 to become the predominant circulating SARS-CoV-2 variant worldwide. Here, we compared the replication fitness of BA.1 and BA.2 in cell culture and in the Syrian hamster model of COVID-19. Using a reverse genetics approach, we found that the BA.1-specific spike mutation G496S compromises its replication fitness, which may contribute to BA.1 being outcompeted by BA.2 in the real world. Additionally, the BA.1-unique G496S substitution confers differentiated sensitivity to therapeutic monoclonal antibodies, which partially recapitulates the immunoevasive phenotype of BA.1 and BA.2. In summary, our study identified G496S as an important determinant during the evolutionary trajectory of SARS-CoV-2.
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http://dx.doi.org/10.1080/22221751.2022.2111977DOI Listing
August 2022

Novel blood derived hemostatic agents for bleeding therapy and prophylaxis.

Curr Opin Hematol 2022 Aug 4. Epub 2022 Aug 4.

Hoxworth Blood Center, University of Cincinnati Academic Health Center.

Purpose Of Review: Hemorrhage is a major cause of preventable death in trauma and cancer. Trauma induced coagulopathy and cancer-associated endotheliopathy remain major therapeutic challenges. Early, aggressive administration of blood-derived products with hypothesized increased clotting potency has been proposed. A series of early- and late-phase clinical trials testing the safety and/or efficacy of lyophilized plasma and new forms of platelet products in humans have provided light on the future of alternative blood component therapies. This review intends to contextualize and provide a critical review of the information provided by these trials.

Recent Findings: The beneficial effect of existing freeze-dried plasma products may not be as high as initially anticipated when tested in randomized, multicenter clinical trials. A next-generation freeze dried plasma product has shown safety in an early phase clinical trial and other freeze-dried plasma and spray-dried plasma with promising preclinical profiles are embarking in first-in-human trials. New platelet additive solutions and forms of cryopreservation or lyophilization of platelets with long-term shelf-life have demonstrated feasibility and logistical advantages.

Summary: Recent trials have confirmed logistical advantages of modified plasma and platelet products in the treatment or prophylaxis of bleeding. However, their postulated increased potency profile remains unconfirmed.
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http://dx.doi.org/10.1097/MOH.0000000000000737DOI Listing
August 2022

Novel blood derived hemostatic agents for bleeding therapy and prophylaxis.

Curr Opin Hematol 2022 Aug 4. Epub 2022 Aug 4.

Hoxworth Blood Center, University of Cincinnati Academic Health Center.

Purpose Of Review: Hemorrhage is a major cause of preventable death in trauma and cancer. Trauma induced coagulopathy and cancer-associated endotheliopathy remain major therapeutic challenges. Early, aggressive administration of blood-derived products with hypothesized increased clotting potency has been proposed. A series of early- and late-phase clinical trials testing the safety and/or efficacy of lyophilized plasma and new forms of platelet products in humans have provided light on the future of alternative blood component therapies. This review intends to contextualize and provide a critical review of the information provided by these trials.

Recent Findings: The beneficial effect of existing freeze-dried plasma products may not be as high as initially anticipated when tested in randomized, multicenter clinical trials. A next-generation freeze dried plasma product has shown safety in an early phase clinical trial and other freeze-dried plasma and spray-dried plasma with promising preclinical profiles are embarking in first-in-human trials. New platelet additive solutions and forms of cryopreservation or lyophilization of platelets with long-term shelf-life have demonstrated feasibility and logistical advantages.

Summary: Recent trials have confirmed logistical advantages of modified plasma and platelet products in the treatment or prophylaxis of bleeding. However, their postulated increased potency profile remains unconfirmed.
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http://dx.doi.org/10.1097/MOH.0000000000000737DOI Listing
August 2022

Association between leucocyte telomere length and the risk of atrial fibrillation: An updated systematic review and meta-analysis.

Ageing Res Rev 2022 Aug 3;81:101707. Epub 2022 Aug 3.

Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, China. Electronic address:

Background And Aims: Advancing age is the most important risk factor of atrial fibrillation (AF). The shortening of telomere length is a biomarker of biologic aging. There is an increasing body of evidence that leucocyte telomere length (LTL) is associated with the risk of AF development. However, the results in these studies were controversial. The current systematic review and meta-analysis was conducted to examine the role of LTL in predicting the incidence of AF.

Methods And Results: Observational studies reporting the association between LTL and the risk of AF were retrieved through 25th June, 2022 from PubMed and Embase. A total of twelve studies including 18,293 patients were included in the present analysis. Leucocyte telomere shortening was found to be an independent predictor of AF as a continuous variable in both univariate [OR:2.14; 95%CI(1.48,3.10); P < 0.0001] and multivariate analyses [OR:1.41;95%CI(1.11,1.79); P = 0.005], as well as categorical variable in multivariate analysis [OR:1.53; 95%CI(1.04,2.27); P = 0.03]. Furthermore, leucocyte telomere shortening was significantly associated with recurrent AF [OR:4.32;95%CI(2.42,7.69); P < 0.00001] but not new-onset AF [OR:1.14; 95%CI(0.90,1.45); P = 0.29]. Leucocyte telomere shortening was also associated with an increased risk of persistent AF [OR:14.73;95%CI (3.16,68.67); P = 0.0006] and paroxysmal AF [OR:2.74;95%CI(1.45,5.18); P = 0.002]. Besides, LTL was an independent predictor for progression from paroxysmal AF to persistent AF [OR:3.2;95%CI(1.66,6.18); P = 0.0005]. Differences between males [OR:1.99; 95%CI(1.29,3.06); P = 0.002] and females [OR:0.86; 95%CI (0.29,2.56);P = 0.79] were observed.

Conclusions: Leucocyte telomere shortening predicts the risk of AF, especially recurrent AF. The predictive value is more prominent in males than in females. Shortening in LTL can predict the progression from paroxysmal to persistent AF.
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http://dx.doi.org/10.1016/j.arr.2022.101707DOI Listing
August 2022

Intrinsically fluorescent polyureas toward conformation-assisted metamorphosis, discoloration and intracellular drug delivery.

Nat Commun 2022 Aug 5;13(1):4551. Epub 2022 Aug 5.

College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, 610065, China.

Peptidomimetic polymers have attracted increasing interest because of the advantages of facile synthesis, high molecular tunability, resistance to degradation, and low immunogenicity. However, the presence of non-native linkages compromises their ability to form higher ordered structures and protein-inspired functions. Here we report a class of amino acid-constructed polyureas with molecular weight- and solvent-dependent helical and sheet-like conformations as well as green fluorescent protein-mimic autofluorescence with aggregation-induced emission characteristics. The copolymers self-assemble into vesicles and nanotubes and exhibit H-bonding-mediated metamorphosis and discoloration behaviors. We show that these polymeric vehicles with ultrahigh stability, superfast responsivity and conformation-assisted cell internalization efficiency could act as an "on-off" switchable nanocarrier for specific intracellular drug delivery and effective cancer theranosis in vitro and in vivo. This work provides insights into the folding and hierarchical assembly of biomacromolecules, and a new generation of bioresponsive polymers and nonconventional luminescent aliphatic materials for diverse applications.
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http://dx.doi.org/10.1038/s41467-022-32053-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355952PMC
August 2022

Enhanced remediation of surface-bound hexavalent chromium in soils using the acidic and alkaline fronts of electrokinetic technology.

Chemosphere 2022 Aug 3;307(Pt 2):135905. Epub 2022 Aug 3.

State Key Laboratory of Coal Mine Disaster Dynamics and Control, Chongqing University, Chongqing 400044, China; College of Resource and Safety Engineering, Chongqing University, Chongqing, 400044, China. Electronic address:

In the subsurface environment, highly toxic hexavalent chromium (Cr(VI)) control and remediation are essential to avoid further ecological impacts and reduce environmental risks. This paper investigated the enhanced Cr(VI) electrokinetic removal in the soil through the approaching cathode method. Besides, a novel four-step sequential fractionation method was used to reflect the strength of Cr(VI) binding to the soil. The approaching cathode enhanced the electrokinetic delivery of surface-bound Cr(VI) by advancing the alkaline front for Cr(VI) desorption and improving the electric potential flattening of the soil layers. Desorption of Cr(VI) by the alkaline front involved converting the inner-sphere complexes form of Cr(VI) to a weakly adsorbed form susceptible to ionic strength. In addition, the acidic front provided a favorable environment for the photochemical reduction of Cr(VI) by soil species or the added citrate as the electron donors. Improving the potential distribution could regulate the energy consumption of individual soil layers and efficiently operate the electrokinetic transfer of pollutants. The work results have significant scientific and practical significance for applying the in-situ electrokinetic technique in subsurface pollution control.
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http://dx.doi.org/10.1016/j.chemosphere.2022.135905DOI Listing
August 2022

Automated multidimensional deep learning platform for referable diabetic retinopathy detection: a multicentre, retrospective study.

BMJ Open 2022 07 28;12(7):e060155. Epub 2022 Jul 28.

Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou, China

Objective: To develop and validate a real-world screening, guideline-based deep learning (DL) system for referable diabetic retinopathy (DR) detection.

Design: This is a multicentre platform development study based on retrospective, cross-sectional data sets. Images were labelled by two-level certificated graders as the ground truth. According to the UK DR screening guideline, a DL model based on colour retinal images with five-dimensional classifiers, namely image quality, retinopathy, maculopathy gradability, maculopathy and photocoagulation, was developed. Referable decisions were generated by integrating the output of all classifiers and reported at the image, eye and patient level. The performance of the DL was compared with DR experts.

Setting: DR screening programmes from three hospitals and the Lifeline Express Diabetic Retinopathy Screening Program in China.

Participants: 83 465 images of 39 836 eyes from 21 716 patients were annotated, of which 53 211 images were used as the development set and 30 254 images were used as the external validation set, split based on centre and period.

Main Outcomes: Accuracy, F1 score, sensitivity, specificity, area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC), Cohen's unweighted κ and Gwet's AC1 were calculated to evaluate the performance of the DL algorithm.

Results: In the external validation set, the five classifiers achieved an accuracy of 0.915-0.980, F1 score of 0.682-0.966, sensitivity of 0.917-0.978, specificity of 0.907-0.981, AUROC of 0.9639-0.9944 and AUPRC of 0.7504-0.9949. Referable DR at three levels was detected with an accuracy of 0.918-0.967, F1 score of 0.822-0.918, sensitivity of 0.970-0.971, specificity of 0.905-0.967, AUROC of 0.9848-0.9931 and AUPRC of 0.9527-0.9760. With reference to the ground truth, the DL system showed comparable performance (Cohen's κ: 0.86-0.93; Gwet's AC1: 0.89-0.94) with three DR experts (Cohen's κ: 0.89-0.96; Gwet's AC1: 0.91-0.97) in detecting referable lesions.

Conclusions: The automatic DL system for detection of referable DR based on the UK guideline could achieve high accuracy in multidimensional classifications. It is suitable for large-scale, real-world DR screening.
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http://dx.doi.org/10.1136/bmjopen-2021-060155DOI Listing
July 2022

Removal of atrazine from submerged soil using vetiver grass ( L.).

Int J Phytoremediation 2022 Jul 28:1-9. Epub 2022 Jul 28.

Faculty of Plant Protection, Yunnan Agricultural University, Kunming, China.

The long-term widespread application of atrazine poses significant threats to the eco-environment and human health. To investigate the potential of vetiver ( L.) for phytoremediation of the environmental media contaminated by atrazine, an indoor incubation experiment was conducted in submerged soil over 30 days. Results showed that the chlorophyll level of the vetiver was not significantly affected by exposure to atrazine. Vetiver could take up and accumulate atrazine from submerged soil and peaked around the 20th day with a concentration of 1.0 mg kg in leaf. The metabolites Hydroxyatrazine (HA), deethylatrazine (DEA), Deisopropylatrazine (DIA), and didealkylatrazine (DDA) were detected in the leaf on the 30th day, indicating vetiver could degrade atrazine inside the leaf tissue. The atrazine removal rate in the vetiver planted and unplanted jars were 69.72 and 60.29%, respectively, indicating that 9.43% higher atrazine removal was achieved in the presence of vetiver ( < 0.05). The atrazine dissipation in the submerged soil followed first-order kinetics, the degradation constant was 0.066, and the half-life of atrazine dissipation was shortened by 6.86 days in the presence of vetiver. The present study suggests that vetiver can take up atrazine from submerged soil and accumulate in the leaf, which could then degrade in the leaf. Although the fate of atrazine in agricultural soils has been extensively investigated through various experiments, little is known about the effect of vetiver grass on atrazine dissipation from submerged soil. With the identification of soil-leaf transportation and four metabolites in vetiver leaf and soils, significantly accelerated atrazine dissipation from the submerged soil was achieved in the presence of vetiver. Particularly, the formation of less toxic dealkylated products in the leaf indicated vetiver is a promising grass for atrazine removal from submerged soil.
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http://dx.doi.org/10.1080/15226514.2022.2103091DOI Listing
July 2022

Risk assessment in systemic lupus erythematosus-associated pulmonary arterial hypertension: CSTAR-PAH cohort study.

Ther Adv Chronic Dis 2022 21;13:20406223221112528. Epub 2022 Jul 21.

Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Wangfujing Ave, Beijing 100730, China.

Objective: This study evaluated the prognostic value of the multivariable risk assessment for systemic lupus erythematosus (SLE)-associated pulmonary arterial hypertension (PAH).

Methods: A multicenter prospective cohort of SLE-associated PAH (CSTAR-PAH cohort) diagnosed based on right heart catheterization (RHC) was established. Baseline and follow-up records were collected. Three methods of risk assessment, including (1) the number of low-risk criteria, based on World Health Organization functional class (WHO FC), 6-min walking distance (6MWD), right atrial pressure (RAP), and cardiac index (CI); (2) the three-strata stratification based on the average risk score of four variables (WHO FC, 6MWD, RAP, and CI); and (3) the four-strata stratification based on COMPARE 2.0 model were applied. A risk-assessment method using three noninvasive low-risk criteria was applied at the first follow-up visit. Survival curves between patients with different risk groups were compared by Kaplan-Meier's estimation and log-rank test.

Results: Three-hundred and ten patients were enrolled from 14 PAH centers. All methods of stratification at baseline and first follow-up significantly discriminated long-term survival. Survival rates were also significantly different based on the noninvasive risk assessment in first follow-up visit. Survival deteriorated with the escalation of risk from baseline to first follow-up. Patients with baseline serositis had a higher rate of risk improvement in their follow-up.

Conclusion: The risk assessment has a significant prognostic value at both the baseline and first follow-up assessment of SLE-associated PAH. A noninvasive risk assessment can also be useful when RHC is not available during follow-up. Baseline serositis may be a predictor of good treatment response in patients with SLE-associated PAH.
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http://dx.doi.org/10.1177/20406223221112528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9310292PMC
July 2022

Kif4A mediates resistance to neoadjuvant chemoradiotherapy in patients with advanced colorectal cancer via regulating DNA damage response.

Acta Biochim Biophys Sin (Shanghai) 2022 May;54(7):1-12

Zhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325000, China.

More and more patients with advanced colorectal cancer (CRC) have benefited from surgical resection or ablation following neoadjuvant chemoradiotherapy (nCRT), but nCRT may be ineffective and have potential risks to some patients. Therefore, it is necessary to discover effective biomarkers for predicting the nCRT efficacy in CRC patients. Chromokinesin Kif4A plays a critical role in mitosis, DNA damage repair and tumorigenesis, but its relationship with nCRT efficacy in advanced CRC remains unclear. Here, we find that Kif4A expression in pretreated tumor tissue is positively correlated with poorer tumor regression after receiving nCRT ( =0.005). Knockdown of endogenous causes an increased sensitivity of CRC cells to chemotherapeutic drugs 5-fluorouracil (5-FU) and Cisplatin (DDP), while overexpression of Kif4A enhances resistance of CRC cells to the chemotherapeutic drugs. Furthermore, depending on its motor domain and tail domain, Kif4A regulates DNA damage response (DDR) induced by 5-FU or DDP treatment in CRC cells. In conclusion, we demonstrate that Kif4A may be a potential independent biomarker for predicting the nCRT efficacy in advanced CRC patients, and Kif4A regulates chemosensitivity of CRC cells through controlling DDR.
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http://dx.doi.org/10.3724/abbs.2022068DOI Listing
May 2022

Development of high-throughput UPLC-MS/MS using multiple reaction monitoring for quantitation of complex human milk oligosaccharides and application to large population survey of secretor status and Lewis blood group.

Food Chem 2022 Jul 20;397:133750. Epub 2022 Jul 20.

Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Key Laboratory of Separation Science for Analytical Chemistry, Dalian 116023, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Human milk oligosaccharides (HMOs) have attracted increasing attention due to the emerging evidence of their positive roles for infant's health. A high-throughput method for absolute quantitation of the complex HMOs including multiple isomeric structures is important but very challenging, due to the highly divers nature and wide variation in content of HMOs from different individuals. Here we used UPLC-MS-MRM in the negative-ion mode for accurate quantitation of 23 complex HMOs in just 15 min. The selected oligosaccharides are in their native forms and include neutral and sialylated, fucosylated and non-fucosylated, linear and branched, and secretor and Lewis phenotype indicators. The well validated method with good sensitivity, recovery and reproducibility was then applied to a large population quantitative survey of 251 Chinese mothers from five different ethnic groups (Han, Zhuang, Hui, Mongolian and Tibetan) living in different geographical regions for their secretor's status and Lewis phenotypes.
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http://dx.doi.org/10.1016/j.foodchem.2022.133750DOI Listing
July 2022

Guideline for the management of pediatric off-label use of drugs in China (2021).

BMC Pediatr 2022 07 23;22(1):442. Epub 2022 Jul 23.

Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China.

Background: The "Law on Doctors of the People's Republic of China," which was officially implemented on March 1, 2022, emphasizes the requirements for rational drug use and the necessity for appropriate management of off-label drug use. The safety and ethical considerations related to off-label drug use are different in children than in adults. There is so far no management guideline for pediatric off-label use of drugs in China, and the applicability of foreign guidelines is limited. Establishing a localized evidence-based management guideline for pediatric off-label use of drugs to support the national legislation and clinical practice is of critical importance.

Methods: We established a guideline working group, including experts from a broad range of disciplines and developed recommendations following the guidance of the World Health Organization Handbook and the Chinese Medical Association. The following themes were identified by questionnaires and expert interviews to be of great concern in the management of off-label drug use in children: general principles and characteristics of management of pediatric off-label drug use; establishment of expert committees; evidence evaluation; risk-benefit assessment; informed consent; monitoring and assessment of the risk; and monitoring and patient education. Two rounds of Delphi surveys were organized to determine the final recommendations of this guideline. We graded the recommendations based on the body of evidence, referring to the evaluation tool of the Evidence-based management (EBMgt) and the Oxford Center for Evidence-Based Medicine: Level of Evidence (March 2009).

Results: We developed the first guideline for the management of pediatric off-label use of drugs in China.

Conclusions: The guideline is to offer guidance for pediatricians, pharmacists, medical managers, policymakers, and primary care physicians on how to manage off-label drug use in pediatrics and to provide recommendations for Chinese healthcare policy in the future.
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http://dx.doi.org/10.1186/s12887-022-03457-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9307429PMC
July 2022

Development and validation of a meta-learning-based multi-modal deep learning algorithm for detection of peritoneal metastasis.

Int J Comput Assist Radiol Surg 2022 Jul 22. Epub 2022 Jul 22.

Institute of Information Science and Electronic Engineering, Zhejiang University, Yuquan Campus, Hangzhou, Zhejiang, China.

Purpose: The existing medical imaging tools have a detection accuracy of 97% for peritoneal metastasis(PM) bigger than 0.5 cm, but only 29% for that smaller than 0.5 cm, the early detection of PM is still a difficult problem. This study is aiming at constructing a deep convolution neural network classifier based on meta-learning to predict PM.

Method: Peritoneal metastases are delineated on enhanced CT. The model is trained based on meta-learning, and features are extracted using multi-modal deep Convolutional Neural Network(CNN) with enhanced CT to classify PM. Besides, we evaluate the performance on the test dataset, and compare it with other PM prediction algorithm.

Results: The training datasets are consisted of 9574 images from 43 patients with PM and 67 patients without PM. The testing datasets are consisted of 1834 images from 21 testing patients. To increase the accuracy of the prediction, we combine the multi-modal inputs of plain scan phase, portal venous phase and arterial phase to build a meta-learning-based multi-modal PM predictor. The classifier shows an accuracy of 87.5% with Area Under Curve(AUC) of 0.877, sensitivity of 73.4%, specificity of 95.2% on the testing datasets. The performance is superior to routine PM classify based on logistic regression (AUC: 0.795), a deep learning method named ResNet3D (AUC: 0.827), and a domain generalization (DG) method named MADDG (AUC: 0.834).

Conclusions: we proposed a novel training strategy based on meta-learning to improve the model's robustness to "unseen" samples. The experiments shows that our meta-learning-based multi-modal PM predicting classifier obtain more competitive results in synchronous PM prediction compared to existing algorithms and the model's improvements of generalization ability even with limited data.
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http://dx.doi.org/10.1007/s11548-022-02698-wDOI Listing
July 2022

Treatment of anal fistula using a decellularized porcine small intestinal submucosa plug: A non-inferiority trial.

Medicine (Baltimore) 2022 Jul 22;101(29):e29110. Epub 2022 Jul 22.

Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.

Background: Using small intestinal submucosa (SIS) has increasingly become the standard method for the treatment of anal fistula. The porcine SIS manufactured by Biosis Healing is a novel biological material that has several advantages for the safe and effective repair of tissues. Our study aimed to verify the efficacy and safety of the decellularized porcine SIS (VIDASIS) anal fistula plug.

Methods: We conducted a non-inferiority multicenter, randomized, controlled clinical trial involving patients with chronic anal fistula. Patients from 3 centers across China were randomized 1:1 to Biosis SIS vs commercial SIS. The primary endpoint was the healing rate and secondary endpoints included recurrence within 6 months, rate of copracrasia, healing time, pain using a visual analog scale, and patient and doctor satisfaction.

Results: A total of 186 patients were randomized. Of these, 82 patients in the Biosis SIS and 81 in the control (commercial) SIS completed the trial (per-protocol set). The healing rate at the 6-month follow-up (full analysis set) was 92.0% for the Biosis SIS and 89.8% for the control SIS (P = .620). The rate difference of 2.2% (full analysis set; 95% confidence interval: -6.4% and 10.7%, respectively) was within the pre-specified non-inferiority margin of -10%. There were no differences between the 2 groups with regard to the secondary endpoints. No serious adverse event or death occurred.

Conclusion: Our study shows that the VIDASIS anal fistula plug manufactured by the company Biosis Healing is safe and effective and is not inferior to existing commercial SIS materials.
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http://dx.doi.org/10.1097/MD.0000000000029110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302366PMC
July 2022

Erythroblastic islands foster granulopoiesis in parallel to terminal erythropoiesis.

Blood 2022 Jul 21. Epub 2022 Jul 21.

Cincinnati Children's Hospital Medical Center and University of Cinicinnati, Cincinnati, Ohio, United States.

The erythroblastic island (EBI), composed of a central macrophage surrounded by maturing erythroblasts, is the erythroid precursor niche. Despite numerous studies, its precise composition is still unclear. Using multispectral imaging flow cytometry (IFC), in vitro island reconstitution, and single cell RNA-sequencing (scRNA-seq) of adult mouse bone marrow EBI-component cells enriched by gradient sedimentation, we present evidence that the CD11b+-cells present in the EBIs are neutrophil precursors specifically associated with bone marrow EBI macrophages, indicating that erythro-(myelo)-blastic islands are a site for both terminal granulopoiesis and erythropoiesis. We further demonstrate that the balance between these dominant and terminal differentiation programs is dynamically regulated within this bone marrow niche by pathophysiological states, favoring granulopoiesis during anemia of inflammation, or erythropoiesis after erythropoietin (Epo) stimulation. Finally, by molecular profiling, we reveal the heterogeneity of EBI macrophages by Cellular Indexing of Transcriptome and Epitopes (CITE)-sequencing of mouse bone marrow EBIs at baseline and after Epo-stimulation in vivo and provide a searchable, online viewer of this data characterizing the macrophage subsets serving as hematopoietic niches. Taken together, our findings demonstrate that EBIs serve a dual role as niches for terminal erythropoiesis and granulopoiesis and the central macrophages adapt to optimize production of red blood cells or neutrophils.
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http://dx.doi.org/10.1182/blood.2022015724DOI Listing
July 2022

DNA Repair Factor Poly(ADP-Ribose) Polymerase 1 Is a Proviral Factor in Hepatitis B Virus Covalently Closed Circular DNA Formation.

J Virol 2022 07 7;96(13):e0058522. Epub 2022 Jun 7.

State Key Laboratory of Virology, Wuhan Institute of Virologygrid.439104.b, Chinese Academy of Sciences, Wuhan, China.

The biogenesis of covalently closed circular DNA (cccDNA) from relaxed circular DNA (rcDNA) is essential for chronic hepatitis B virus (HBV) infection. Different host DNA repair proteins are involved in the conversion of rcDNA to cccDNA. Here, we reported that the DNA repair factor poly(ADP-ribose) polymerase 1 (PARP1) is engaged in HBV cccDNA formation. PARP1 depletion remarkably impaired HBV replication and cccDNA synthesis. Inhibition of PARP1 poly (ADP-ribosylation) activity by olaparib suppressed cccDNA synthesis both and . Specifically, the early stage of cccDNA reservoir establishment was more sensitive to olaparib, suggesting that PARP1 participated in cccDNA formation. Furthermore, PARP1 was activated by recognizing the rcDNA-like lesions directly and combined with other DNA repair proteins. The results presented proposed that the DNA damage-sensing protein PARP1 and poly(ADP-ribosylation) modification play a key role in cccDNA formation, which might be the target for developing the anti-HBV drug. The biogenesis and eradication of HBV cccDNA have been a research priority in recent years. In this study, we identified the DNA repair factor PARP1 as a host factor required for the HBV cccDNA formation. HBV infection caused PARylation through PARP1 in Huh7-NTCP cells, primary human hepatocytes, and human-liver chimeric mice. We found that PARP1 could directly bind to the rcDNA lesions and was activated, PARylating other DNA repair proteins. We address the importance of PARP1-mediated PARylation in HBV cccDNA formation, which is a potential therapeutic target for chronic hepatitis B.
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http://dx.doi.org/10.1128/jvi.00585-22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9278152PMC
July 2022

Clarithromycin-treated chronic spontaneous urticaria with the negative regulation of FcεRΙ and MRGPRX2 activation via CD300f.

Int Immunopharmacol 2022 Jul 16;110:109063. Epub 2022 Jul 16.

School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China. Electronic address:

Mast cells (MCs) are main effector cells in chronic spontaneous urticaria (CSU). Both Fc epsilon RI (FcεRΙ)- and MAS-related G coupled receptor-X2 (MRGPRX2)-mediated MC activations affect CSU course. Leukocyte mono-immunoglobulin-like receptor 3 (CD300f) has been shown to regulate FcεRΙ activation. However, no study has verified CD300f is a target to cure CSU. Therefore this study aimed to verify whether clarithromycin (CLA) regulates FcεRΙ- and MRGPRX2-mediated MC activations via CD300f and shows therapeutic effect on CSU. The target of CLA was verification. CLA inhibited FcεRΙ- and MRGPRX2-mediated MC activations were shown in vivo and in vitro. A single-center, self-comparison study was performed, and CLA-treated CSU was investigated in 28 patients who were not sensitive to the third-generation antihistamines. Serum inflammatory mediators in patients before and after CLA administration were analyzed. CLA effectively inhibited type Ι anaphylactic reactions and pseudo-allergic reactions in mice. Moreover, CLA inhibited FcεRΙ- and MRGPRX2-mediated MC signaling pathway activation. Regulatory effects of CLA were decreased significantly after CD300f knockdown. CLA effectively alleviated the symptoms of wheal and itch and reduced serum cytokine levels in patients. CLA negatively regulated FcεRΙ- and MRGPRX2-mediated MC activation via CD300f and showed significant therapeutic effect on CSU.
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http://dx.doi.org/10.1016/j.intimp.2022.109063DOI Listing
July 2022

Tumor specificity of WNT ligands and receptors reveals universal squamous cell carcinoma oncogenes.

BMC Cancer 2022 Jul 19;22(1):790. Epub 2022 Jul 19.

Department of Health Management, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610054, China.

Background: The WNT signal pathway has myriad family members, which are broadly involved in embryonic development and human cancer. Over-activation of WNT-β-Catenin signaling promotes cancer cell proliferation and survival. However, how diverse components of WNT signaling specifically engaged in distinct tumor types remains incompletely understood.

Methods: We analyzed the transcriptomic profiling of WNT ligands and receptors/co-receptors among 26 different tumor types to identify their expression pattern, and further verified these results using clinical oral squamous cell carcinoma (OSCC) and lung squamous cell carcinoma (LUSC) samples. At the same time, we also detected WNT7B expression in oral inflammation and carcinoma, and constructed stable WNT7B knockdown OSCC cell lines to study the effects of WNT7B on the cell migration and invasion ability.

Results: We found a group of tumor-specific WNT members, including a panel of squamous cell carcinomas (SCCs) specific upregulated WNT ligands and receptors, WNT5A, WNT7B, FZD7 and GPC1. We further revealed a significant correlation between these protein expression characteristics and clinical outcomes of OSCC and LUSC patients. Moreover, WNT7B was demonstrated to contribute to the development of oral chronic inflammation and OSCC, partly due to promoting the invasion ability of tumor cells.

Conclusions: These results demonstrate that the function of WNT ligands and receptors in specific tumors depends on the origination of tumor tissue type. Collectively, they support the use of WNT components as a highly specific target for pan-tissue-type originated tumors.
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http://dx.doi.org/10.1186/s12885-022-09898-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9295300PMC
July 2022

Low-Energy Electron Damage to Plasmid DNA in Thin Films: Dependence on Substrates, Surface Density, Charging, Environment, and Uniformity.

J Phys Chem B 2022 Jul 14;126(29):5443-5457. Epub 2022 Jul 14.

Département de Médecine Nucléaire et Radiobiologie et Centre de Recherche Clinique, Faculté de Médecine, Université de Sherbrooke, Sherbrooke, Quebec J1H 5N4, Canada.

The interaction of low-energy electrons (LEEs) with DNA plays a significant role in the mechanisms leading to biological damage induced by ionizing radiation, particularly in radiotherapy, and its sensitization by chemotherapeutic drugs and nanoparticles. Plasmids constitute the form of DNA found in mitochondria and appear as a suitable model of genomic DNA. In a search for the best LEE targets, damage was induced to plasmids, in thin films in vacuum, by 6, 10, and 100 eV electrons under single collision conditions. The yields of single- and double-strand breaks, other cluster damage, isolated base lesions, and crosslinks were measured by electrophoresis and enzyme treatment. The films were deposited on oriented graphite or polycrystalline tantalum, with or without DNA autoassembly via diaminopropane (Dap) intercalation. Yields were correlated with the influence of vacuum, film uniformity, surface density, substrates, and the DNA environment. Aided by surface potential measurements and scanning electron microscopy and atomic force microscopy images, the lyophilized Dap-DNA films were found to be the most practical high-quality targets. These studies pave the way to the fabrication of LEE target-films composed of plasmids intercalated with biomolecules that could mimic the cellular environment; for example, as a first step, by replacing Dap with an amino acid.
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http://dx.doi.org/10.1021/acs.jpcb.2c03664DOI Listing
July 2022

Buddy Balloon versus Buddy Wire Technique Regarding Accuracy of Stent Placement during Percutaneous Coronary Intervention.

Int Heart J 2022 Jul 14;63(4):654-660. Epub 2022 Jul 14.

Institute of Cardiovascular Diseases of PLA, Department of Cardiology, Xinqiao Hospital, Army Medical University (Third Military Medical University).

We aimed to evaluate whether the buddy balloon technique (BBT) is superior to the buddy wire technique (BWT) with regard to the accuracy of stent placement during percutaneous coronary intervention (PCI).We enrolled patients who had been identified with significant stent movement before the stent was dilated at five hospitals and were randomly converted to either the BBT or BWT technique. The primary endpoints were the incidence of technical success and major adverse cardiovascular events (cardiac death, myocardial infarction, target lesion revascularization, and in-stent restenosis) at 2 years of follow-up. The secondary endpoints were the contrast volume used for the procedure and the total procedural time.From August 2018 to July 2019, 66 patients were enrolled, with 33 patients in each group. All patients were successfully followed up to 2 years. At the primary endpoints, compared with patients treated using BWT, those in the BBT group showed significantly better technical success (93.94% versus 39.39%, respectively; P < 0.0001). There was no significant difference in the incidence of major cardiovascular adverse events (6.06% versus 12.12%, respectively; P = 0.392). At the secondary endpoints, the contrast volume used for the procedure was lower with BBT (85.97 ± 22.45 versus 115.00 ± 21.45 mL, respectively; P < 0.0001); similarly, the total procedural time was shorter with BBT (65.94 ± 12.14 versus 74.33 ± 15.36 minutes, respectively; P < 0.0001).BBT could better restrict stent movement and facilitate precise stent deployment, with significant superiority over BWT. In addition, BBT can reduce the procedural time and contrast dose.
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http://dx.doi.org/10.1536/ihj.21-841DOI Listing
July 2022

Autism-associated chromatin remodeler CHD8 regulates erythroblast cytokinesis and fine-tunes the balance of Rho GTPase signaling.

Cell Rep 2022 Jul;40(2):111072

Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229, USA. Electronic address:

CHD8 is an ATP-dependent chromatin-remodeling factor whose monoallelic mutation defines a subtype of autism spectrum disorders (ASDs). Previous work found that CHD8 is required for the maintenance of hematopoiesis by integrating ATM-P53-mediated survival of hematopoietic stem/progenitor cells (HSPCs). Here, by using Chd8Mx1-Cre combined with a Trp53 mouse model that suppresses apoptosis of Chd8 HSPCs, we identify CHD8 as an essential regulator of erythroid differentiation. Chd8P53 mice exhibited severe anemia conforming to congenital dyserythropoietic anemia (CDA) phenotypes. Loss of CHD8 leads to drastically decreased numbers of orthochromatic erythroblasts and increased binucleated and multinucleated basophilic erythroblasts with a cytokinesis failure in erythroblasts. CHD8 binds directly to the gene bodies of multiple Rho GTPase signaling genes in erythroblasts, and loss of CHD8 results in their dysregulated expression, leading to decreased RhoA and increased Rac1 and Cdc42 activities. Our study shows that autism-associated CHD8 is essential for erythroblast cytokinesis.
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http://dx.doi.org/10.1016/j.celrep.2022.111072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302451PMC
July 2022

Amiodarone/N-desethylamiodarone population pharmacokinetics in paediatric patients.

Br J Clin Pharmacol 2022 Jul 11. Epub 2022 Jul 11.

EA7323 Pediatric and perinatal drug evaluation and pharmacology, Université de Paris, Paris, France.

The population pharmacokinetics of amiodarone and its active metabolite, N-desethylamiodarone (DEA) were investigated in paediatric patients with arrhythmias, mainly supraventricular tachycardias. A total of 55 patients from the Department of Pediatric Intensive Care and Pediatric Cardiology at Necker-Enfants malades Hospital (Paris, France) provided 72 concentrations for both amiodarone and DEA following repeated oral or intravenous administration. Blood samples drawn for biological analyses were used for drug concentrations. Plasma amiodarone concentrations were measured by a liquid chromatography method coupled with mass spectrometry and the data were modelled using the software Monolix 2019R2. Parent pharmacokinetics was described with a 2-compartment open model and the metabolite formation was connected to the central parent compartment. Parameter estimates scaled allometrically on bodyweight (normalized to 70 kg) were, respectively (% relative standard errors, RSEs), 6.32 (31%) and 7.14 L/h (26%) for elimination (CL) and intercompartmental clearances and 167 (31%) and 3930 (32%) L for V and V . Oral bioavailability was 0.362 (21.5%). The clearance between subject variability (ω, square root of the variance) was 0.462 (RSE 21%). The proportional residual variabilities were respectively 0.453 (RSE 13%) and 0.423 (RSE 12%) for amiodarone and DEA respectively. The terminal half-lives were 34 and 14.5 days for amiodarone and DEA, respectively. A dosage schedule was established for 3 weight bands in 2 time periods. The high pharmacokinetic variability suggests that therapeutic drug monitoring might be useful to improve individual efficacy and safety.
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http://dx.doi.org/10.1111/bcp.15458DOI Listing
July 2022

Lilac (Syringa oblata) genome provides insights into its evolution and molecular mechanism of petal color change.

Commun Biol 2022 Jul 9;5(1):686. Epub 2022 Jul 9.

Beijing Advanced Innovation Center for Tree Breeding by Molecular Design, The Key Laboratory for Silviculture and Conservation of the Ministry of Education, National Engineering Research Center of Tree Breeding and Ecological Restoration, Key Laboratory of Genetics and Breeding in Forest Trees and Ornamental Plants of Ministry of Education, College of Forestry, College of Biological Sciences and Technology, Beijing Forestry University, Beijing, 100083, China.

Color change during flower opening is common; however, little is understood on the biochemical and molecular basis related. Lilac (Syringa oblata), a well-known woody ornamental plant with obvious petal color changes, is an ideal model. Here, we presented chromosome-scale genome assembly for lilac, resolved the flavonoids metabolism, and identified key genes and potential regulatory networks related to petal color change. The genome assembly is 1.05 Gb anchored onto 23 chromosomes, with a BUSCO score of 96.6%. Whole-genome duplication (WGD) event shared within Oleaceae was revealed. Metabolome quantification identified delphinidin-3-O-rutinoside (Dp3Ru) and cyanidin-3-O-rutinoside (Cy3Ru) as the major pigments; gene co-expression networks indicated WRKY an essential regulation factor at the early flowering stage, ERF more important in the color transition period (from violet to light nearly white), while the MBW complex participated in the entire process. Our results provide a foundation for functional study and molecular breeding in lilac.
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http://dx.doi.org/10.1038/s42003-022-03646-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271065PMC
July 2022

A Resilience Analysis of a Medical Mask Supply Chain during the COVID-19 Pandemic: A Simulation Modeling Approach.

Int J Environ Res Public Health 2022 Jun 30;19(13). Epub 2022 Jun 30.

School of Management, Xihua University, Chengdu 610039, China.

The COVID-19 pandemic has caused severe consequences such as long-term disruptions and ripple effects on regional and global supply chains. In this paper, firstly, we design simulation models using AnyLogistix to investigate and predict the pandemic's short-term and long-term disruptions on a medical mask supply chain. Then, the Green Field Analysis experiments are used to locate the backup facilities and optimize their inventory levels. Finally, risk analysis experiments are carried out to verify the resilience of the redesigned mask supply chain. Our major research findings include the following. First, when the pandemic spreads to the downstream of the supply chain, the duration of the downstream facilities disruption plays a critical role in the supply chain operation and performance. Second, adding backup facilities and optimizing their inventory levels are effective in responding to the pandemic. Overall, this paper provides insights for predicting the impacts of the pandemic on the medical mask supply chain. The results of this study can be used to redesign a medical mask supply chain to be more resilient and flexible.
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http://dx.doi.org/10.3390/ijerph19138045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9265473PMC
June 2022

Role of ATP-dependent chromatin remodelers in hematopoietic stem and progenitor cell maintenance.

Authors:
Zhaowei Tu Yi Zheng

Curr Opin Hematol 2022 07 18;29(4):174-180. Epub 2022 Feb 18.

Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

Purpose Of Review: ATP-dependent chromatin remodeling factors utilize energy from ATP hydrolysis to modulate DNA-histone structures and regulate gene transcription. They are essential during hematopoiesis and for hematopoietic stem and progenitor cell (HSPC) function. This review discusses the recently unveiled roles of these chromatin remodelers in HSPC regulation, with an emphasis on the mechanism of chromodomain helicase DNA-binding (CHD) family members.

Recent Findings: Recent studies of ATP-dependent chromatin remodelers have revealed that individual CHD family members engage in distinct mechanisms in regulating HSPC cell fate. For example, CHD8 is required for HSPC survival by restricting both P53 transcriptional activity and protein stability in steady state hematopoiesis while the related CHD7 physically interacts with RUNX family transcription factor 1 (RUNX1) and suppresses RUNX1-induced expansion of HSPCs during blood development. Moreover, other CHD subfamily members such as CHD1/CHD2 and CHD3/CHD4, as well as the switch/sucrose non-fermentable, imitation SWI, and SWI2/SNF2 related (SWR) families of chromatin modulators, have also been found important for HSPC maintenance by distinct mechanisms.

Summary: The expanding knowledge of ATP-dependent chromatin remodelers in hematopoiesis illustrates their respective critical roles in HSPC maintenance including the regulation of HSPC differentiation, survival, and self-renewal. Further studies are warranted to elucidate how different chromatin remodeling complexes are integrated in various HSPC cell fate decisions during steady-state and stress hematopoiesis.
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http://dx.doi.org/10.1097/MOH.0000000000000710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9257093PMC
July 2022

Exploration of Mutated Genes and Prediction of Potential Biomarkers for Childhood-Onset Schizophrenia Using an Integrated Bioinformatic Analysis.

Front Aging Neurosci 2022 16;14:829217. Epub 2022 Jun 16.

The National Clinical Research Center for Mental Disorders and Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China.

Childhood-onset schizophrenia (COS) is an unusual severe neurodevelopmental disorder of unknown etiology. In this study, we aimed to survey the missense variants in new cases of COS and also identify possible pathology biomarkers for COS. We found one list of mutated genes such as TTN, MUC12, and MUC2, which are the candidates to be involved in the etiology of COS. Next, we used WGSNA to predict COS disease-related genes and identified differential DNA methylation among COS disease groups, COS dangerous groups, and normal groups and found eight methylation sites that can be used as the diagnostic biomarkers. A total of six key genes are obtained through the intersection analysis between weighted correlation network analysis (WGCNA) mode, methylation-related genes, and differentially expressed genes (DGenes). These genes may play important roles in the progression of COS and serve as the potential biomarkers for future diagnosis. Our results might help to design the molecule or gene-targeted drugs for COS.
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http://dx.doi.org/10.3389/fnagi.2022.829217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9243414PMC
June 2022
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