Publications by authors named "Qiong Chen"

478 Publications

Co-evolutionary adaptations of and a clinical carbapenemase-encoding plasmid during carbapenem exposure.

Evol Appl 2022 Jul 5;15(7):1045-1061. Epub 2022 Jul 5.

Department of Infectious Diseases, School of Medicine Sir Run Run Shaw Hospital Zhejiang University Hangzhou China.

OXA-23 is the predominant carbapenemase in carbapenem-resistant . The co-evolutionary dynamics of and OXA-23-encoding plasmids are poorly understood. Here, we transformed ATCC 17978 with pAZJ221, a -containing plasmid from clinical isolate A221, and subjected the transformant to experimental evolution in the presence of a sub-inhibitory concentration of imipenem for nearly 400 generations. We used population sequencing to track genetic changes at six time points and evaluated phenotypic changes. Increased fitness of evolving populations, temporary duplication of in pAZJ221, interfering allele dynamics, and chromosomal locus-level parallelism were observed. To characterize genotype-to-phenotype associations, we focused on six mutations in parallel targets predicted to affect small RNAs and a cyclic dimeric (3' → 5') GMP-metabolizing protein. Six isogenic mutants with or without pAZJ221 were engineered to test for the effects of these mutations on fitness costs and plasmid kinetics, and the evolved plasmid containing two copies of was transferred to ancestral ATCC 17978. Five of the six mutations contributed to improved fitness in the presence of pAZJ221 under imipenem pressure, and all but one of them impaired plasmid conjugation ability. The duplication of increased host fitness under carbapenem pressure but imposed a burden on the host in antibiotic-free media relative to the ancestral pAZJ221. Overall, our study provides a framework for the co-evolution of and a clinical -containing plasmid in the presence of imipenem, involving early duplication followed by chromosomal adaptations that improved the fitness of plasmid-carrying cells.
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http://dx.doi.org/10.1111/eva.13441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309461PMC
July 2022

Inhibitory Control of Emotional Interference in Deaf Children: Evidence From Event-Related Potentials and Event-Related Spectral Perturbation Analysis.

Front Psychiatry 2022 24;13:897595. Epub 2022 Jun 24.

Department of Health Promotion, Education, and Behavior, University of South Carolina, Columbia, SC, United States.

Background: Impairment of interference control ability may reflect a more general deficit in executive functioning, and lead to an increase in internal-externalized problems such as impulsivity, which has been reported in deaf children. However, few researches have examined the neural mechanism of this impairment.

Methods: This study applied the electroencephalogram (EEG) technique to investigate the interference control ability in 31 deaf children and 28 hearing controls with emotional face-word stroop task.

Results: Results from behavioral task showed that deaf children exhibited lower accuracy compared to hearing controls. As for EEG analysis, reduced activation of ERP components in N1 and enhanced activation of ERP components in N450 have been found in deaf children. Besides, incongruent condition elicited larger N450 than congruent condition. Furthermore, for brain oscillation, alpha band (600-800 ms) revealed a reduced desynchronization in deaf children, while theta band (200-400 ms) revealed an enhanced synchronization in deaf children and incongruent condition, which were in line with ERP components.

Conclusion: The present findings seem to indicate that the deficit during emotional interference control ability among deaf children might be due to the impaired attention allocation ability and emotional cognitive monitoring function during emotional conflict detection process. Consequently, reduced N1 and enhanced N450 might be due to early attention impairment causing more effort of deaf children later in emotional cognitive monitoring.
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http://dx.doi.org/10.3389/fpsyt.2022.897595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263210PMC
June 2022

Pelvic bones ADC could help to predict severe hematologic toxicity in patients undergoing concurrent chemoradiotherapy for cervical cancer.

Magn Reson Imaging 2022 Jun 28. Epub 2022 Jun 28.

Department of Radiology, Cancer Hospital of China Medical University, Xiaoheyan road 44#, Shenyang Liaoning 110042, China. Electronic address:

Background: Hematologic toxicity (HT) during concurrent chemoradiotherapy (CCRT) for cervical cancer can lead to treatment breaks and compromise efficacy.

Purpose: To evaluate the association between severe hematologic toxicity (HT) and clinical factors and pelvic apparent diffusion coefficient (ADC) during CCRT of cervical cancer patients.

Methods: Data from 120 patients with cervical cancer who were treated with CCRT from January 2016 and December 2018 were retrospectively analyzed. The clinical data (age, menopausal status, clinical stage, body mass index, chemotherapy regimen and chemotherapy cycle) of the patients were collected, and the cohort were divided into two groups based on the HT grade: HT3+ group (HT grade ≥ 3; 66 patients) and HT3- group (HT grade<3; 54 patients). All patients performed MRI before CCRT, and pelvic (ilium, pubis, ischium) ADC value was measured on ADC map. The correlation between severe HT and clinical parameters and pelvic ADC value were analyzed by univariate analysis, and the diagnostic performance was further assessed by receiver operating characteristic (ROC) analysis.

Results: In univariate analysis, the menopausal status (p = 0.012) and chemotherapy regimen (p = 0.011) were significantly correlated with severe HT in overall patients, and menopausal patients or patients receiving paclitaxel plus cisplatin (TP) regimen were more likely to develop severe HT. HT3+ group showed a significantly lower pelvic ADC value than HT3- group. The ADC value cut-offs derived from our study for predicting severe HT was 0.317 × 10 mm/s in overall patients. Neither clinical parameters or pelvic ADCs were associated with severe HT in menopausal patients when analyzed separately (p > 0.05).

Conclusions: Severe HT was significantly associated with menopausal status and chemotherapy regimen in patients with cervical cancer treated with CCRT, and HT3+ group showed a lower pelvic ADC value.
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http://dx.doi.org/10.1016/j.mri.2022.06.007DOI Listing
June 2022

Establishment and application of a quadruple real-time RT-PCR for detecting avian metapneumovirus.

PLoS One 2022 28;17(6):e0270708. Epub 2022 Jun 28.

China Animal Health and Epidemiology Center, Qingdao, Shandong, China.

In order to develop an appropriate method for high-throughput detection of avian metapneumovirus, a quadruple real-time reverse-transcription polymerase chain reaction assay was established with four pairs of specific primers and four specific probes based on the G or M gene of aMPV-A, aMPV-B, aMPV-C and aMPV-D. Its specificity and sensitivity were evaluated, and clinical samples were tested by the method. The results showed that all the four subgroups of avian metapneumovirus can be detected in the quadruple real-time RT-PCR assay simultaneously, with a detection limit of 100-1000 cRNA copies/reaction. The other common poultry viruses were negative. In the avian clinical sample detection, 39 out of 1920 clinical samples collected from 8 provinces were positive. Compared with published RT-PCR assays, the κ value of the quadruple real-time RT-PCR assay in 1920 avian clinical samples was 1.000 (P < 0.001). The established method could be used for the rapid detection of the four subgroups of avian metapneumovirus with high specificity and high sensitivity.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0270708PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9239461PMC
June 2022

A trefoil knot self-templated through imination in water.

Nat Commun 2022 06 21;13(1):3557. Epub 2022 Jun 21.

Department of Chemistry, Zhejiang University, Hangzhou, 310027, PR China.

The preparation of topologically nontrivial molecules is often assisted by covalent, supramolecular or coordinative templates that provide spatial pre-organization for all components. Herein, we report a trefoil knot that can be self-assembled efficiently in water without involving additional templates. The direct condensation of three equivalents of a tetraformyl precursor and six equivalents of a chiral diamine produces successfully a [3 + 6] trefoil knot whose intrinsic handedness is dictated by the stereochemical configuration of the diamine linkers. Contrary to the conventional wisdom that imine condensation is not amenable to use in water, the multivalent cooperativity between all the imine bonds within the framework makes this trefoil knot robust in the aqueous environment. Furthermore, the presence of water is proven to be essential for the trefoil knot formation. A topologically trivial macrocycle composed of two tetraformyl and four diamino building blocks is obtained when a similar reaction is performed in organic media, indicating that hydrophobic effect is a major driving force behind the scene.
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http://dx.doi.org/10.1038/s41467-022-31289-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213439PMC
June 2022

Elevational shifts in foliar-soil δ N in the Hengduan Mountains and different potential mechanisms.

Glob Chang Biol 2022 Jun 17. Epub 2022 Jun 17.

Key Laboratory of Soil Ecology and Health in Universities of Yunnan Province, School of Ecology and Environmental Sciences, Yunnan University, Kunming, P.R. China.

The natural abundance of stable nitrogen isotopes (δ N) provides insights into the N dynamics of terrestrial ecosystems, the determination of which is considered an effective approach for gaining a better understanding ecosystem N cycling. However, there is currently little information available regarding the patterns and mechanisms underlying the variation in foliar-soil δ N among mountain ecosystems. In this study, we examined the determinants of foliar-soil δ N in association with N transportation rates along an elevational gradient in the Hengduan Mountains. Despite the relatively high levels of available N produced from high N fixation and mineralization, we detected the lowest levels of foliar δ N at 3500 m a.s.l., reflecting the stronger vegetation N limitation at medium high elevations. The enhanced vegetation N limitation was driven by the combined effects of higher microbial immobilization and inherent plant dynamic (the shifts of δ N in vegetation preference, including vegetation community) with changing climate along the elevational gradient. Unexpectedly, we established that soil δ N was characterized by an undulating rise and uncoupled correlation with foliar δ N with increasing elevation, thereby indicating that litter input might not be a prominent driver of soil δ N. Conversely, soil nitrification and denitrification were found to make a more pronounced contribution to the pattern of soil δ N along the elevational gradient. Collectively, our results serve to highlight the importance of microbial immobilization in soil N dynamics and provide novel insights that will contribute to enhancing our understanding of N cycling as indicated by foliar-soil δ N along elevational gradients.
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http://dx.doi.org/10.1111/gcb.16306DOI Listing
June 2022

N6-methyladenosine (m6A) regulator expression pattern correlates with the immune landscape in lung adenocarcinoma.

Gene 2022 Aug 11;836:146639. Epub 2022 Jun 11.

Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, China; Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, China; Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, China; Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, China. Electronic address:

Lung adenocarcinoma is the leading cause of tumor-related death. The tumor microenvironment (TME) may determine anti-tumor treatment responses. We focused on 23 m6A regulators, and analyzed m6A regulator expression patterns in 995 lung adenocarcinoma samples collected from 7 publicly available datasets. Two m6A clusters were identified, wherein gene clusters and m6A score were generated using unsupervised clustering and principal component analysis based on differentially expressed genes with prognostic significance. Further, three independent datasets from TCGA-LUAD and GEO were employed to validate the impact of m6A signatures and score. We found that m6A cluster 1 with high m6A score was associated with an inflamed TME, higher neoantigen and tumor mutation burden and improved response to immunotherapy. However, anti-tumor immunity cells were exhausted in high m6A score patients; thus, the prognosis of these patients was poor. Elucidation of m6A regulator expression pattern may facilitate the development of effective treatment strategies for lung adenocarcinoma.
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http://dx.doi.org/10.1016/j.gene.2022.146639DOI Listing
August 2022

Efficacy and Safety of Direct-Acting Antivirals in Kidney Transplantation From HCV-Viremic Donors to Negative Recipients: A Meta-Analysis.

Front Med (Lausanne) 2022 18;9:802686. Epub 2022 May 18.

Department of Infectious Diseases, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Background: With the development of direct-acting antiviral agents (DAAs), the research on kidney transplantation from Hepatitis C virus (HCV)-viremic donors to HCV-negative recipients has grown. The objective of this comprehensive analysis was to evaluate the efficacy and safety of DAAs in kidney transplantation from HCV-viremic donors to negative recipients.

Methods: Multiple databases were searched for a systematic and comprehensive up to March 2022. The primary outcomes included the percentage of sustained virological response at week 12 after the end of treatment (SVR12), adverse events (AEs; any grade), and severe adverse events (SAEs) as the endpoints. Publication bias was examined by using the funnel plots and Egger's test.

Results: In total, 16 studies with 454 subjects were included in the study and the pooled estimate of SVR12, AEs, and SAEs rates were 100.0% (95% CI: 99.2-100.0), 1.9%(95%CI: 0.0-4.9), and 0.0% (95%CI: 0.0-1.5). Subgroup analysis showed that pooled SVR12 rates were 100.0% (95%CI: 99.6-100.0) for genotype (GT)1a and 96.3% (95%CI: 83.3-100.0) for GT2; 100.0% (95%CI: 98.9-100.0) for DAAs treatments; and 100.0% (95%CI: 98.2-100.0) for prophylaxis subgroup. Egger's tests showed that no publication bias was found in this study.

Conclusion: This comprehensive analysis showed the high efficacy and safety of DAAs in kidney transplantation from HCV-viremic donors to HCV-negative recipients.

Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=246541.
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http://dx.doi.org/10.3389/fmed.2022.802686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9158331PMC
May 2022

Management of Malnutrition Based on Multidisciplinary Team Decision-Making in Chinese Older Adults (3M Study): A Prospective, Multicenter, Randomized, Controlled Study Protocol.

Front Nutr 2022 9;9:851590. Epub 2022 May 9.

Department of Geriatrics, Xuanwu Hospital Capital Medical University, Beijing, China.

Background: In hospital settings, malnutrition affects 30-50% of aged inpatients and is related to a higher risk of hospital complications and death. This study aims to demonstrate the effectiveness of a tailored optimum nutritional therapy in malnourished, elderly inpatients based on multidisciplinary team recommendations in hopes of decreasing the incidence of deleterious clinical outcomes.

Methods And Design: This trial will be a multicenter, open-label, randomized control trial conducted in the geriatric wards of at least five hospitals in five different regions. We aim to include 500 inpatients over the age of 60 with or at risk of malnutrition based on a Mini Nutritional Assessment Short-Form (MNA-SF) score of ≤ 11 points and the Global Leadership Initiative on Malnutrition with an expected length of stay of ≥ 7 days. Eligible inpatients will be randomized into a 1:1 ratio, with one receiving a multidisciplinary team intervention and the other receiving standard medical treatment or care alone. A structured comprehensive assessment of anthropometry, nutritional status, cognition, mood, functional performance, and quality of life will be conducted twice. These assessments will take place on the day of group allocation and 1 year after discharge, and a structured screening assessment for elderly malnutrition will be conducted at 3 and 6 months after discharge using the MNA-SF. The primary outcome will be nutritional status based on changes in MNA-SF scores at 3, 6 months, and 1 year. The secondary outcome will be changes in cognition, mood, functional status, length of hospital stay, and all-cause mortality 1 year after discharge.

Discussion: Guided by the concept of interdisciplinary cooperation, this study will establish a multidisciplinary nutrition support team that will develop an innovative intervention strategy that integrates nutritional screenings, evaluations, education, consultation, support, and monitoring. Moreover, nutritional intervention and dietary fortification will be provided to hospitalized elderly patients with or at risk of malnutrition. The nutrition support team will formulate a clinical map for malnutrition in elderly patients with standardized diagnosis and treatment for malnutrition in this population.

Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [ChiCTR2200055331].
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http://dx.doi.org/10.3389/fnut.2022.851590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9150743PMC
May 2022

Effect Observation of Electro-Acupuncture Anesthesia Combined with General Anesthesia in Elderly Patients Undergoing Gastrointestinal Tumor Resection.

Front Surg 2022 12;9:901638. Epub 2022 May 12.

Department of Anesthesiology, Yongkang First People's Hospital, Jinhua City, China.

Objective: To investigate the anesthetic effect of electro-acupuncture (EA) anesthesia combined with general anesthesia in elderly patients undergoing gastrointestinal tumor resection, and to analyze the effects of EA anesthesia on inflammatory factors, stress state and T lymphocyte subsets in elderly patients.

Methods: Total of 118 elderly patients who underwent gastrointestinal tumor resection in our hospital from June 2018 to March 2021 were selected and divided into the control group (59 cases) and the observation group (59 cases) according to the random number method. General anesthesia was adopted in the control group and EA anesthesia combined with general anesthesia was adopted in the observation group. The anesthesia effect, stress state, levels of inflammatory factors, T-lymphocyte subsets and adverse reactions were compared.

Results: The VAS score, agitation score and respiratory normalization time in the observation group were lower than those in the control group ( < 0.05). After surgery, the levels of serum Cor, ET, NE and DA in the observation group were lower than those in the control group ( < 0.05). At 24 h after surgery, the levels of serum TNF-α, IL-6 and IL-1β in the observation group were lower than those in the control group ( < 0.05). At 24 h after surgery, the levels of , , and in the two groups were lower than those before surgery, and the levels of , , and in the observation group were higher than those in the control group ( < 0.05). During the hospitalization, the total incidence rate of adverse reactions after anesthesia in the observation group was lower than that in the control group ( < 0.05).

Conclusion: EA anesthesia combined with general anesthesia has good anesthesia effect when used for gastrointestinal tumor resection in the elderly. It can stabilize the internal environment of patients, alleviate postoperative stress response and inflammatory response, and regulate the body immune function. Moreover, it has high safety and can significantly reduce the occurrence of postoperative adverse reactions.
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http://dx.doi.org/10.3389/fsurg.2022.901638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9134448PMC
May 2022

Application of the FreeStyle®Libre Glucose Monitoring System in type 1 diabetes mellitus patients aged 1-4 years.

Pediatr Diabetes 2022 Aug 14;23(5):604-610. Epub 2022 Jun 14.

Department of Endocrinology, Genetics and Metabolism, Henan Children's Hospital, Zhengzhou Children's Hospital, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou, China.

Background: To investigate the analytical accuracy, safety performance, and user satisfaction (guardians of study participants) of the FreeStyle®Libre Glucose Monitoring System in the treatment of type 1 diabetes mellitus (T1DM), in children aged <4 years.

Methods: Sixteen hospitalized children with new onset T1DM, aged 4 months to 4 years, were enrolled in this study. Patients wore the sensor for 14 days; sensor scans were performed immediately and at 5, 10, and 15 min after capillary blood glucose (BG) measurements to evaluate the effectiveness of the device and the lag effect.

Results: The consensus error grid showed that 96.40% of values fell within zone A (no clinical impact) and 3.60% within zone B (little/no clinical impact). Overall, the mean absolute relative difference (MARD) was 9.34%, and was higher in the capillary BG <4.0 mmol/L group (15.18%) than in the 4-10 mmol/L (9.63%) and >10 mmol/L (7.17%) groups. The MARD increased gradually with scanning time extension, indicating a short lag effect. Regression analysis showed that a higher BG level was associated with a greater difference in FreeStyle®Libre System measurements.

Conclusions: The use of the FreeStyle®Libre System in children aged 1-4 years is accurate and safe, and may be accurate down to 4 months, independent of patient characteristics.
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http://dx.doi.org/10.1111/pedi.13368DOI Listing
August 2022

Identification of Three Genes Associated with Metastasis in Melanoma and Construction of a Predictive Model: A Multiracial Identification.

J Oncol 2022 21;2022:4567063. Epub 2022 May 21.

Department of Plastic Surgery, Dermatology Hospital of Fuzhou, Fuzhou, China.

The aim of this study was to identify hub genes associated with metastasis and prognosis in melanoma. Weighted gene coexpression network analysis (WGCNA) was performed to screen and identify hub genes. ROC and K-M analyses were used to verify the hub genes in the internal and external data sets. The risk score model and nomogram model were constructed based on the IHC result. Through WGCNA, the three hub genes, SNRPD2, SNRPD3, and EIF4A3, were identified. In the external data set, the hub genes identified were associated with the worse prognosis (TCGA, SNRPD2, ≤ 0.02; SNRPD3, = 0.12; EIF4A3, = 0.11; GSE65904, SNRPD2, = 0.04; SNRPD3, = 0.10; EIF4A3, < 0.01; GSE19234, SNRPD2, < 0.01; SNRPD3, < 0.01; EIF4A3, < 0.01). In the GSE8401, we found that the hub genes were highly expressed in the metastasis compared with the nonmetastasis group (SNRPD2, 988.5 ± 47.83 vs. 738.4 ± 35.35, < 0.01; SNRPD3, 502.7 ± 25.7 vs. 416.4 ± 23.88, = 0.02; EIF4A3, 567.6 ± 19.56 vs. 495.2 ± 21.1, = 0.01). Moreover, the hub genes were identified by the IHC in our data set. The result was similar with the external data set. The hub genes could predict the metastasis and prognosis in the Chinese MM patients. Finally, the GSEA and Pearson analysis demonstrated that the SNRPD2 was associated with the immunotherapy. The three hub genes were identified and validated in MM patients in external and internal data sets. The risk factor model was constructed and verified as a powerful model to predict metastasis and prognosis in MM patients.
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http://dx.doi.org/10.1155/2022/4567063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9148232PMC
May 2022

Pharmacophore-Oriented Discovery of Novel 1,2,3-Benzotriazine-4-one Derivatives as Potent 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors.

J Agric Food Chem 2022 Jun 26;70(22):6644-6657. Epub 2022 May 26.

Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, International Joint Research Center for Intelligent Biosensor Technology and Health, College of Chemistry, Central China Normal University, Wuhan 430079, P. R. China.

4-Hydroxyphenylpyruvate dioxygenase (HPPD) is a functional protein existing in almost all aerobic organisms. In the field of agricultural chemicals, HPPD is acknowledged to be one of the crucial targets for herbicides at present due to its unique bio-function in plants. In the Auto Core Fragment Screening (ACFIS) web server, a potential HPPD inhibitor featuring 1,2,3-benzotriazine-4-one was screened out via a pharmacophore-linked fragment virtual screening (PFVS) method. Molecular simulation studies drove the process of "hit-to-lead" optimization, and a family of 1,2,3-benzotriazine-4-one derivatives was synthesized. Consequently, 6-(2-hydroxy-6-oxocyclohex-1-ene-1-carbonyl)-5-methyl-3-(2-methylbenzyl)benzo[][1,2,3]triazin-4(3)-one () was identified to be the best HPPD inhibitor (IC = 36 nM) among the 1,2,3-benzotriazine-4-one derivatives, which had over 8-fold improvement of enzyme inhibition compared with the positive control mesotrione (IC = 289 nM). Crystallography information for the HPPD- complex revealed several important interactions of the ligand bound upon the target protein, i.e., the bidentate chelating interaction of the triketone motif with the metal ion of HPPD, a tight π-π stacking interaction consisting of the1,2,3-benzotriazine-4-one moiety and two benzene rings of Phe-424 and Phe-381, and the polydirectional hydrophobic contacts consisting of the -CH-benzyl group of the core scaffold and some hydrophobic residues. Furthermore, compound displayed 100% inhibition against the five species of target weeds at the tested dosage, which was comparable to the weed control of mesotrione. Collectively, the fused 1,2,3-benzotriazine-4-one-triketone hybrid is a promising chemical tool for the development of more potent HPPD inhibitors and provides a valuable lead compound for herbicide innovation.
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http://dx.doi.org/10.1021/acs.jafc.2c01507DOI Listing
June 2022

Transesophageal Echocardiography Following Left Atrial Appendage Electrical Isolation: Diagnostic Pitfalls and Clinical Implications.

Circ Arrhythm Electrophysiol 2022 06 26;15(6):e010975. Epub 2022 May 26.

Texas Cardiac Arrhythmia Institute, St David's Medical Center, Austin (C.G., J.E.S., Q.C., D.G.D., S.M., C.T., A.A.-A., M.A.B., J.D.B., G.J.G., R.P.H., P.M.H., L.D.B., A.N.).

Background: Following left atrial appendage (LAA) electrical isolation, the decision on whether to continue oral anticoagulation after successful atrial fibrillation ablation is based on the study of its mechanical function on transesophageal echocardiography (TEE). In this cohort, LAA contraction is absent and the incorrect interpretation of emptying flow velocities can lead to unwanted clinical sequelae.

Methods: One hundred and sixty consecutive TEE exams performed to evaluate the LAA mechanical function following its electrical isolation were reviewed by an experienced operator blinded to the original diagnosis of LAA dysfunction. The rate of diagnostic discrepancy in the assessment LAA dysfunction and its clinical implications were evaluated.

Results: Diagnostic discrepancy with misclassification of the LAA mechanical function occurred 36% (58/160) of TEE exams. In most cases (57/58), such discrepancy was observed in the setting of an incorrect original diagnosis of a normal LAA mechanical function despite absent/reduced or inconsistent LAA contraction. This main source of this wrong diagnosis was the wrong interpretation of passive LAA flows (34/57; 60%), followed by failure to identify dissociated firing (15/57; 26%). In rare cases (8/57; 14%), velocities of surrounding structures were interpreted as LAA flow due to misplacement of the pulsed-wave Doppler sample volume. Following LAA isolation, the proportion of patients who experienced a cerebrovascular event while off oral anticoagulation due to the misclassification of their LAA mechanical function was 70% (7/10 [95% CI, 40%-89%]).

Conclusions: Underdiagnosis of LAA mechanical dysfunction is common in TEEs performed following LAA electrical isolation, and it is associated with an increased risk of cerebrovascular events owing to oral anticoagulation discontinuation despite absent/reduced LAA contraction. Careful review of the TEE exam by an operator with specific expertise in LAA imaging and familiar with the functional implications of LAA isolation is necessary before interrupting oral anticoagulation in this cohort.
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http://dx.doi.org/10.1161/CIRCEP.122.010975DOI Listing
June 2022

TFR1 expression in induced sputum is associated with asthma severity.

PeerJ 2022 17;10:e13474. Epub 2022 May 17.

National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Background: Asthma is characterized as a chronic inflammatory airway disease. Iron accumulation is related to asthma pathogenesis. Transferrin receptor 1(TFR1) expression is associated with intracellular iron overload in macrophages. In our study, we explored the association among TFR1 expression, the inflammatory macrophage phenotype, and asthma severity.

Methods: Induced sputum was collected from 50 asthma patients. Real-time PCR was used to evaluate mRNA expression. The status of inflammatory macrophage phenotype was assessed using flow cytometry.

Results: TFR1 levels were inversely correlated with forced expiratory volume in 1 s (FEV)/forced vital capacity (FVC) and FEV/vital capacity (VC). Among inflammatory cytokines, TFR1 expression was positively correlated with IL-1β, TNF-α, IL-6, IFN-γ, and IL-17A mRNA expression in induced sputum. Moreover, TFR1 expression was positively correlated with the number of proinflammatory M1 macrophages and iNOS expression in induced sputum. Neutrophil counts in induced sputum were significantly and positively related to TFR1 expression. Furthermore, TFR1 expression showed an increasing trend in asthma patients with no family history. Our findings indicated that TFR1 expression was consistent with the asthma severity index, especially the proinflammatory M1 macrophage phenotype. TFR1 expression may be a good marker to indicate asthma severity.
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http://dx.doi.org/10.7717/peerj.13474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9121881PMC
May 2022

Neutrophil Count Predicts Malignant Cerebellar Edema and Poor Outcome in Acute Basilar Artery Occlusion Receiving Endovascular Treatment: A Nationwide Registry-Based Study.

Front Immunol 2022 3;13:835915. Epub 2022 May 3.

Department of Neurology, Xinqiao Hospital and The Second Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, China.

Background: Acute basilar artery occlusion (ABAO) is known to have a poor outcome with a high rate of morbidity and mortality despite endovascular treatment (EVT), highlighting the necessities of exploring factors to limit the efficacy of EVT in these patients. Cerebellar infarctions in ABAO might progress to malignant cerebellar edema (MCE), a life-threatening complication after reperfusion, posing a secondary injury to the brainstem by mass effects. Therefore, the present research aimed to explore the impacts of MCE on a long-term outcome and investigate the prognostic factors for MCE among ABAO after EVT.

Methods: In the national BASILAR registry, a total of 329 ABO patients with cerebellar infarctions treated by EVT met the inclusion criteria. The presence of MCE defined by the Jauss scale ≥4 points, was evaluated on the computed tomography performed 72 h after EVT. The adjusted odds ratio and 95% CI were obtained by logistic regression models. A favorable outcome was defined as a 90-day modified Rankin Scale score of 0-3.

Results: MCE was statistically associated with the decreased incidence of a favorable outcome [adjusted odds ratio, 0.35(95% CI, 0.18-0.68), P=0.002]. The baseline National Institutes of Health Stroke Scale score, collateral circulation, neutrophil count at admission, and recanalization status were predictors for MCE and a favorable functional status at 90 days (all P<0.05). Among all inflammatory factors, the neutrophil count achieved the highest accuracy, sensitivity, and specificity for MCE. Adding the neutrophil count status into the baseline model obviously enhanced its prediction ability for MCE and favorable outcome by increasing the area under curve and achieving both net reclassification and integrated discrimination improvement (all P<0.05). Mediation analysis indicated that MCE mediated the association between the increased neutrophil count and worse functional outcome (P=0.026).

Discussion: MCE acted essential roles in worsening prognosis for ABAO after EVT. A high neutrophil count at admission was linked to MCE and a poor outcome among ABAO patients, which could be further incorporated into the clinical decision-making system and guide immunomodulation therapy.
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http://dx.doi.org/10.3389/fimmu.2022.835915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9111017PMC
May 2022

Redistribution of Histone Marks on Inflammatory Genes Associated With Intracerebral Hemorrhage-Induced Acute Brain Injury in Aging Rats.

Front Neurosci 2022 15;16:639656. Epub 2022 Apr 15.

Department of Neurology, Xinqiao Hospital, The Army Medical University (Third Military Medical University), Chongqing, China.

The contribution of histone mark redistribution to the age-induced decline of endogenous neuroprotection remains unclear. In this study, we used an intracerebral hemorrhage (ICH)-induced acute brain injury rat model to study the transcriptional and chromatin responses in 13- and 22-month-old rats. Transcriptome analysis (RNA-seq) revealed that the expression of neuroinflammation-associated genes was systematically upregulated in ICH rat brains, irrespective of age. Further, we found that interferon-γ (IFN-γ) response genes were activated in both 13- and 22-month-old rats. Anti-IFN-γ treatment markedly reduced ICH-induced acute brain injury in 22-month-old rats. At the chromatin level, ICH induced the redistribution of histone modifications in the promoter regions, especially H3K4me3 and H3K27me3, in neuroinflammation-associated genes in 13- and 22-month-old rats, respectively. Moreover, ICH-induced histone mark redistribution and gene expression were found to be correlated. Collectively, these findings demonstrate that histone modifications related to gene expression are extensively regulated in 13- and 22-month-old rats and that anti-IFN-γ is effective for ICH treatment, highlighting the potential of developing therapies targeting histone modifications to cure age-related diseases, including brain injury and neuroinflammation.
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http://dx.doi.org/10.3389/fnins.2022.639656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9051396PMC
April 2022

Novel poly(epichlorohydrin)-based matrix for monolithic ionogel electrolyte membrane with high lithium storage performances.

RSC Adv 2022 Apr 21;12(19):12160-12165. Epub 2022 Apr 21.

College of Materials Science and Engineering, South China University of Technology Guangzhou 510640 China

Based on gelling matrices and ionic liquids (ILs), monolithic ionogel electrolyte membranes (MIEMs) have become a research focus. However, further application is limited by lack of functional matrices. Herein, we proposed the introduction of an ionized polymer, , polyether polymer with side-chain ionic groups obtained the reaction of quaternary ammonium with uncrystallizable poly (epichlorohydrin) (PECH), as the matrix into the gels to balance the mechanical properties and the ionic conductivity. In combination with lithium bis-(fluorosulfonyl) imide (LiFSI) and 1-ethyl-3-methylimidazolium bis-(fluorosulfonyl)-imide (EMImFSI) a solvent casting technique, a flexible MIEM was successfully prepared. The as-obtained MIEM exhibited good thermal stability (up to about 250 °C) and a high ionic conductivity of 1.21 mS cm at 20 °C. Moreover, Li|LiFePO coin cells using this MIEM delivered high capacity (150.0 mA h g at 0.2C) with good cycling stability, and an excellent C-rate response. This work discloses a novel and paramount route to exploit PECH-based MIEMs for Li storage, as well as energy storage systems beyond Li.
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http://dx.doi.org/10.1039/d2ra00110aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9022508PMC
April 2022

Study on the Association of Homocysteine and C-Reactive Protein with Neurofunctional Changes in Patients with Acute Ischemic Stroke After Endovascular Stent Treatment.

Neuropsychiatr Dis Treat 2022 13;18:881-889. Epub 2022 Apr 13.

Clinical Laboratory Medicine Center, Zhongshan City People Hospital, Zhongshan, 528400, People's Republic of China.

Objective: To examine the association of homocysteine (HCY) and C-reactive protein (CRP) with neurofunctional changes in patients with acute ischemic stroke (AIS) after stent treatment.

Methods: A total of 110 patients with AIS treated with stents were divided into a high HCY group (n = 59) and a normal HCY group (n = 51) based on the HCY level. Pearson correlation analysis and logistic linear regression analysis were used to analyze the related factors that affect the National Institutes of Health Stroke Scale (NIHSS) score changes after stent treatment.

Results: (1) The area under the receiver operating characteristic (ROC) curve for HCY was 0.995 (95% confidence interval [CI]: 0.984-1.005, = 0.000), and the best predictive value was 12.75 µmol/L (sensitivity 89.9%, specificity 98.0%). The area under the ROC curve for CRP was 0.665 (95% CI: 0.564-0.767, = 0.003), and the best predictive value was 9.7 mg/L; (2) comparison between the high HCY group and the normal HCY group showed statistical differences ( < 0.05) in HCY, CRP, and the NIHSS score at admission, the NIHSS score after treatment, gender, history of diabetes, and history of atrial fibrillation; (3) both HCY and CRP were proven to be correlated with the NIHSS score after treatment (0.188, = 0.050) and (0.194, = 0.042), respectively, using Pearson correlation analysis; (4) HCY, low-density lipoprotein, CRP, cystatin C, glucose, history of atrial fibrillation, history of diabetes, and the NIHSS score at admission as the risk factors.

Conclusion: High HCY and CRP levels are related to the neurofunctional changes in patients with AIS treated with stents and can be used as indicators to assess the risk of treating AIS with stents and as serum markers to predict prognoses.
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http://dx.doi.org/10.2147/NDT.S356331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9014111PMC
April 2022

Incidence of Newly Diagnosed Type 1 Diabetes Mellitus in Children and Adolescents in Henan Province of China from 2017 to 2020: A Retrospective Multicenter Study Based on Hospitalization Data.

J Clin Res Pediatr Endocrinol 2022 Apr 19. Epub 2022 Apr 19.

Department of Endocrinology, Genetics and Metabolism, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Henan, China.

Background: The incidence of type 1 diabetes mellitus (T1DM) is rapidly increasing worldwide. However, the incidence in Henan Province of China has been unknown for more than two decades. This study aimed to estimate the incidence of T1DM in the 0.5-14.9 years age group in Henan Province of China from 2017 to 2020.

Methods: A retrospective analysis of hospital registration data from 18 cities in Henan Province, China, identified 1726 patients (843 males, 883 females) between 0.5-14.9 years of age with newly diagnosed T1DM in Henan Province from January 1st, 2017, to December 31st, 2020, covering more than 19 million children years at risk.

Results: The crude incidence of T1DM per 100 000 person years for the 0.5-14.9 years age group in the Henan Province of China was 2.19 (95% confidence interval (CI): 1.99, 2.40), with a peak in the 10-14.9 years age group. The rate ratio of females to males was 1.32 (95% CI: 1.20, 1.45) in the 0.5-14.9 years age group. The incidence rate was higher in females than males in the 5-9.9 years age group (P˂0.01) and the 10-14.9 years age group (P˂0.01). The seasonality of the incidence was different from that in previous reports, with the lowest incidence in the spring.

Conclusion: The incidence of T1DM in the 0.5-14.9 years age group in Henan Province of China was still among the lowest reported according to our study.
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http://dx.doi.org/10.4274/jcrpe.galenos.2022.2021-12-4DOI Listing
April 2022

Application of per-Residue Energy Decomposition to Design Peptide Inhibitors of PSD95 GK Domain.

Front Mol Biosci 2022 30;9:848353. Epub 2022 Mar 30.

Department of Pharmaceutical Chemistry, Third Military Medical University, Chongqing, China.

Specific interaction between the postsynaptic density protein 95 (PSD95) and synapse-associated protein 90/postsynaptic density 95-associated protein (SAPAP) is crucial for excitatory synaptic development and plasticity. Designing inhibitors that target the guanylate kinase (GK) domain of PSD95, which is responsible for the interaction, is a promising manipulation tool for the investigation of the function of PSD95 GK and the etiology of its related psychiatric disorders. Herein, we designed new peptide inhibitors of PSD95 GK/SAPAP with higher binding affinity by using molecular dynamics simulations. First, the interactions between PSD95 GK and their reported phosphorylated and unphosphorylated peptides were explored by molecular dynamics simulations. Besides the hydrogen bonding interactions mediated by the phospho-serine (p-Ser) or corresponding phosphomimic residue Asp/Glu, the hydrophobic interactions from the other amino acids also contribute to the PSD95 GK/SAPAP interaction. As an unphosphorylated synthetic peptide with moderate binding affinity and relatively lower molecular weight, the QSF inhibitory peptide was selected for further modification. Based on per-residue energy decomposition results of the PSD95 GK/QSF complex, ten peptides were designed to enhance the binding interactions, especially the hydrophobic interactions. The top-ranked five peptides with lower binding energy were eventually synthesized. The binding affinities of the synthesized peptides were determined using fluorescence polarization (FP) assay. As expected, all peptides have higher binding affinity than the QSF peptide ( = 5.64 ± 0.51 μM). Among them, F10W was the most potent inhibitor ( = 0.75 ± 0.25 μM), suggesting that enhancement of the hydrophobic interactions is an important strategy for the design of new inhibitory peptides targeting PSD95 GK.
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http://dx.doi.org/10.3389/fmolb.2022.848353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9005747PMC
March 2022

SLC25A38 as a novel biomarker for metastasis and clinical outcome in uveal melanoma.

Cell Death Dis 2022 Apr 11;13(4):330. Epub 2022 Apr 11.

Department of Genetic Engineering, Beijing Institute of Biotechnology, Beijing, 100850, China.

Risk of metastasis is increased by the presence of chromosome 3 monosomy in uveal melanoma (UM). This study aimed to identify more accurate biomarker for risk of metastasis in UM. A total of 80 patients with UM from TCGA were assigned to two groups based on the metastatic status, and bioinformatic analyses were performed to search for critical genes for risk of metastasis. SLC25A38, located on chromosome 3, was the dominant downregulated gene in metastatic UM patients. Low expression of SLC25A38 was an independent predictive and prognostic factor in UM. The predictive potential of SLC25A38 expression was superior to that of pervious reported biomarkers in both TCGA cohort and GSE22138 cohort. Subsequently, its role in promoting metastasis was explored in vitro and in vivo. Knock-out of SLC25A38 could enhance the migration ability of UM cells, and promote distant metastasis in mice models. Through the inhibition of CBP/HIF-mediated pathway followed by the suppression of pro-angiogenic factors, SLC25A38 was situated upstream of metastasis-related pathways, especially angiogenesis. Low expression of SLC25A38 promotes angiogenesis and metastasis, and identifies increased metastatic risk and worse survival in UM patients. This finding may further improve the accuracy of prognostic prediction for UM.
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http://dx.doi.org/10.1038/s41419-022-04718-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9001737PMC
April 2022

Peripheral Blood Mononuclear Cell Gene Expression in Chronic Obstructive Pulmonary Disease: miRNA and mRNA Regulation.

J Inflamm Res 2022 1;15:2167-2180. Epub 2022 Apr 1.

Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.

Introduction: The mechanisms underlying chronic obstructive pulmonary disease (COPD) remain unclear. Genetic and genomic changes may play a significant role in the pathogenesis of COPD. Identification of differentially expressed genes and miRNAs and their regulatory mechanisms at the whole-genome level will provide a comprehensive understanding of the development of COPD.

Methods: Peripheral blood mononuclear cells (PBMCs) from 12 patients with COPD and 12 normal controls were examined at the miRNA and mRNA expression levels using Affymetrix GeneChip. Microarray data were analyzed with Affymetrix Transcriptome Analysis Console 2.0 and GeneSpring software. Gene interaction pathways of the differentially expressed genes and miRNA-mRNA regulation were analyzed using the Ingenuity Pathway Analysis software. Four differentially expressed genes and one miRNA were further confirmed using RT-qPCR.

Results: One hundred and thirty-three upregulated and 973 downregulated genes were identified in PBMCs of patients with COPD. Pathway analysis on the differentially expressed genes in COPD revealed significant enrichment in IL-8 signaling and iCOS-iCOSL signaling in T helper cells. Seventy-seven upregulated miRNAs and 43 downregulated miRNAs were differentially expressed between PBMCs from patients with COPD and normal controls. Among these 120 differentially expressed miRNAs, 42 miRNAs targeting 28 upregulated genes and 69 miRNAs targeting 498 downregulated genes were identified. The expression of CXCR1, HBEGF, TREM-1, and hsa-miR-148a-3p was more elevated in patients with COPD than in normal controls, whereas NFAT5 was decreased.

Conclusion: miRNAs and mRNAs are differentially expressed in PBMCs of patients with COPD, compared with normal controls. miRNAs regulate the expression of mRNAs, and thus play a role in the pathogenesis of COPD. Investigating these relationships may provide further insight into the mechanisms of COPD.
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http://dx.doi.org/10.2147/JIR.S337894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8983057PMC
April 2022

Chromatin-remodeling factor CHR721 with non-canonical PIP-box interacts with OsPCNA in Rice.

BMC Plant Biol 2022 Apr 1;22(1):164. Epub 2022 Apr 1.

College of Life Sciences, Henan Normal University, Xinxiang, China.

Background: Proliferating cell nuclear antigen (PCNA) is one of the key factors for the DNA replication process and DNA damage repair. Most proteins interacting with PCNA have a common binding motif: PCNA interacting protein box (PIP box). However, some proteins with non-canonical PIP-box have also been reported to be the key factors that interacted with PCNA.

Results: Here we discovered the C terminal of a chromatin-remodeling factor CHR721 with non-canonical PIP-box was essential for interacting with OsPCNA in rice. Both OsPCNA and CHR721 were localized in the nuclei and function in response to DNA damages.

Conclusions: Based on the results and previous work, we proposed a working model that CHR721 with non-canonical PIP-box interacted with OsPCNA and both of them probably participate in the DNA damage repair process.
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http://dx.doi.org/10.1186/s12870-022-03532-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8974069PMC
April 2022

Special issue "The advance of solid tumor research in China": Participants with a family history of cancer have a higher participation rate in low-dose computed tomography for lung cancer screening.

Int J Cancer 2022 Apr 1. Epub 2022 Apr 1.

Department of Cancer Epidemiology and Prevention, Henan Engineering Research Center of Cancer Prevention and Control, Henan International Joint Laboratory of Cancer Prevention, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.

We aimed to determine participation in low-dose computed tomography (LDCT) of individuals with a family history of common cancers in a population-based screening program to provide timely evidence in high-risk populations in China. The analysis was conducted using data from the Cancer Screening Program in Urban China (CanSPUC), which recruited 282 377 participants aged 40 to 74 years from eight cities in the Henan province. Using the CanSPUC risk score system, 55 428 participants were evaluated to have high risk for lung cancer and were recommended for LDCT. We calculated the overall and group-specific participation rates using family history of common cancers and compared differences in participation rates between different groups. Odds ratios (ORs) and 95% confidence intervals were derived by multivariable logistic regression. Of the 55 428 participants, 22 260 underwent LDCT (participation rate, 40.16%). Family history of lung, esophageal, stomach, liver and colorectal cancer was associated with increased participation in LDCT screening. The odds of participants with a family history of one, two, three and four or more cancer cases undergoing LDCT screening were 1.9, 2.7, 2.8 and 3.5 times, respectively, than those without a family history of cancer. Compared to those without a history of cancer, participation in LDCT gradually increased as the number of cancer cases in the family increased (P < .001). Our findings suggest that there is room for improvement in lung cancer screening given the relatively low participation rate. Lung cancer screening in populations with a family history of cancer may improve efficiency and cost-effectiveness; however, this requires further verification.
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http://dx.doi.org/10.1002/ijc.34010DOI Listing
April 2022

Simulation-based training in asthma exacerbation for medical students: effect of prior exposure to simulation training on performance.

BMC Med Educ 2022 Mar 31;22(1):223. Epub 2022 Mar 31.

Department of Gerontology and Respirology, Xiangya Hospital of Central South University, Changsha, 410008, Hunan, China.

Objectives: To evaluate the effect of prior exposure to simulation-based training on medical students' performance in simulation-based training in asthma exacerbation.

Methods: Third-year novice medical students, who had no prior experience in simulation education and completed diagnostics and internal medicine courses, were recruited in this prospective observational study and divided into the pre-exposure and unexposed groups. Each group received a four-hour asthma exacerbation simulation-based training. The pre-exposure group was exposed to a myocardial infarction simulation training two weeks prior to the asthma simulation training. The main outcome was the performance scores in clinical skills and abilities. Performance and task checklist completion were recorded during the training. In addition, the knowledge level was tested before and after the simulation training. Students' satisfaction was evaluated using a feedback questionnaire.

Results: In a class of 203 third-year novice medical students, 101 (49.8%) and 102 (50.2%) were assigned to the unexposed and pre-exposure groups, respectively. Scores were higher in the post-simulation test compared with the pre-simulation test. Checklist completion was greater in the pre-exposure group compared with the unexposed group (p < 0.001). Performances in communication and medical humanistic care were better in the pre-exposure group than in the unexposed group (p < 0.001). There were no differences in medical history taking, physical examination, auxiliary examination interpretation and treatment formulation between the two groups (p > 0.001). Totally 73.21% and 26.13% of students strongly agreed and agreed, respectively, that asthma exacerbation simulation-based training was necessary and valuable.

Conclusions: Prior exposure to simulation training can improve performance in medical students, including communication skills, medical humanistic care and checklist completion in subsequent asthma exacerbation simulation-based training.
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http://dx.doi.org/10.1186/s12909-022-03300-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8973632PMC
March 2022

Functional carbon nanodots improve soil quality and tomato tolerance in saline-alkali soils.

Sci Total Environ 2022 Jul 25;830:154817. Epub 2022 Mar 25.

School of Materials Science and Engineering, Harbin Institute of Technology (Shenzhen), Shenzhen 518055, PR China; Research Center for Carbon Nanomaterials, Key Laboratory for Liquid-Solid Structural Evolution & Processing of Materials (Ministry of Education), School of Materials Science and Engineering, Shandong University, Jinan 250061, PR China. Electronic address:

High salinity and alkalinity of saline-alkali soil lead to soil deterioration, the subsequent osmotic stress and ion toxicity inhibited crops growth and productivity. In this research, 8 mg kg and 16 mg kg functional carbon nanodots (FCNs) can alleviate the adverse effects of saline-alkali on tomato plant at both seedling and harvest stages, thanks to their up-regulation effects on soil properties and plant physiological processes. On one hand, FCNs stimulate the plant potential of tolerance to saline-alkali and disease resistance through triggering the defense response of antioxidant system, enhancing the osmotic adjustment, promoting the nutrient uptake, transportation and utilization, and up-regulating the photosynthesis, thereby improve tomato growth and productivity in saline-alkali soils. On the other hand, FCNs application contributes to the improvement of soil physicochemical properties and fertilities, as well as decline soil salinity and alkalinity, which are related to plant growth and fruit quality. This research also focuses on the dose-dependent effects of FCNs on their regulation effects and toxicity to tomato growth under stress or non-stress. These findings recommend that FCNs could be applied as potential amendments to ameliorate the saline-alkali soil and improve the tomato tolerance and productivity in the Yellow River Delta.
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http://dx.doi.org/10.1016/j.scitotenv.2022.154817DOI Listing
July 2022

FGF4, A New Potential Regulator in Gestational Diabetes Mellitus.

Front Pharmacol 2022 4;13:827617. Epub 2022 Mar 4.

Department of Infectious Diseases & Zhejiang Provincial Key laboratory of Liver Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Gestational diabetes mellitus (GDM) is associated with adverse maternal and neonatal outcomes, however the underlying mechanisms remain elusive. The aim of this study was to find efficient regulator of FGFs in response to the pathogenesis of GDM and explore the role of the FGFs in GDM. We performed a systematic screening of placental FGFs in GDM patients and further in two different GDM mouse models to investigate their expression changes. Significant changed FGF4 was selected, engineered, purified, and used to treat GDM mice in order to examine whether it can regulate the adverse metabolic phenotypes of the diabetic mice and protect their fetus. We found FGF4 expression was elevated in GDM patients and its level was positively correlated to blood glucose, indicating a physiological relevance of FGF4 with respect to the development of GDM. Recombinant FGF4 (rFGF4) treatment could effectively normalize the adverse metabolic phenotypes in high fat diet induced GDM mice but not in STZ induced GDM mice. However, rFGF4 was highly effective in reduce of neural tube defects (NTDs) of embryos in both the two GDM models. Mechanistically, rFGF4 treatment inhibits pro-inflammatory signaling cascades and neuroepithelial cell apoptosis of both GDM models, which was independent of glucose regulation. Our study provides novel insight into the important roles of placental FGF4 and suggests that it may serve as a promising diagnostic factor and therapeutic target for GDM.
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http://dx.doi.org/10.3389/fphar.2022.827617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8934430PMC
March 2022

Corrigendum: Construction and Validation of a Lung Cancer Risk Prediction Model for Non-Smokers in China.

Front Oncol 2022 3;12:871848. Epub 2022 Mar 3.

Department of Cancer Epidemiology and Prevention, Henan Engineering Research Center of Cancer Prevention and Control, Henan International Joint Laboratory of Cancer Prevention, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.

[This corrects the article DOI: 10.3389/fonc.2021.766939.].
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http://dx.doi.org/10.3389/fonc.2022.871848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8928720PMC
March 2022

Clinical, Biochemical, Molecular, and Outcome Features of Mitochondrial 3-Hydroxy-3-Methylglutaryl-CoA Synthase Deficiency in 10 Chinese Patients.

Front Genet 2021 4;12:816779. Epub 2022 Mar 4.

Department of Endocrinology and Metabolism, Henan Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China.

Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency (HMGCS2D) is a rare autosomal recessive metabolic disorder caused by mutations of the gene. To date, no more than 60 patients have been reported throughout the world. : To analyze the clinical, biochemical, molecular, and outcome features of HMGCS2D in a case series of 10 new Chinese patients. This retrospective study includes 10 Chinese patients diagnosed with HMGCS2D. We collected and analyzed clinical data for all patients. We also reviewed clinical data for 39 cases that had been reported previously. All of our patients had experienced their first metabolic crisis before 12 months old. The most common clinical manifestations were anorexia, dyspnea, and disturbance of consciousness (10/10), followed by vomiting (8/10), fever (7/10), cough (4/10), diarrhea, and seizures (3/10). Each patient (10/10) had a different degree of hepatomegaly and increased aminotransferase, severe metabolic acidosis, and hypofibrinogenemia. 9 patients presented with severe hypoglycemia and weak positives on qualitative tests of urinary ketone body. Patient 3 was the only one without hypoglycemia. Five patients had hypocalcemia, five patients had hyperammonemia, four patients had hyperuricemia, and three had hypertriglyceridemia. During the metabolic acidosis episode, we observed high dicarboxylic acid values in urine, and the elevated ratio of blood acetylcarnitine to free carnitine may have been an additional biochemical signature. However, all returned to normal during the interictal interval. Molecular analysis identified 15 variants in the gene, of which 10 were novel (c.220G>A/p.E74K, c.407A>G/p.D136G, c.422T>A/p.V141D, c.719A>C/p.D240A, c.821G>A/p.R274H, c.39dupA/p.L14Tfs*59, c.1394delA/p.N465Tfs*10, c.788delT/p.L263Cfs*36, c.717T>G/p.Y239*, and c.1017-2A>G). Combining these with previous cases, the known mutation c.1201G>T/p.E401* has been found in 6/40 (15.0%) of mutated alleles in 21 Chinese patients from 20 families, while none have been found in other populations. We found that patients with biallelic truncation mutation appeared to show a more severe clinical condition through a literature review. This study analyzed the phenotypic and genetic features of HMGCS2D in a Chinese case series. We also expanded the mutational spectrum with 10 novel variants. The c.1201G>T/p.E401* mutation was the most frequent, representing 15.0% of the mutated alleles in reported unrelated Chinese patients, and thus, it may be a hot spot mutation.
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http://dx.doi.org/10.3389/fgene.2021.816779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8931749PMC
March 2022
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