Publications by authors named "Xuemei Wang"

819 Publications

Appropriateness of Empirical Fluoroquinolones Therapy in Patients Infected with , , or : The Importance of the CLSI Breakpoints Revision.

Infect Drug Resist 2021 31;14:3541-3552. Epub 2021 Aug 31.

Department of Nosocomial Infection Management, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, People's Republic of China.

Purpose: Empirical antibiotic therapy should follow the local bacterial susceptibility, and the breakpoints revisions of the antimicrobial susceptibility testing can reflect the changes in the antimicrobial susceptibility of bacteria. This study aimed to analyze whether the changes in the antimicrobial susceptibility to antibiotics caused by the breakpoint revision will affect the empirical antibiotic therapy and its appropriateness.

Patients And Methods: A retrospective study was conducted among 831 hospitalized patients infected by , , and from April 10, 2018, to April 11, 2020. We evaluated the appropriateness of empirical therapy based on the antimicrobial susceptibility testing results. The rate of empirical use and appropriateness of fluoroquinolones was calculated, and logistic regression was used to analyze influencing factors of empirical use of fluoroquinolones.

Results: The susceptibility rate of the three bacteria to levofloxacin (50.78% vs 32.06%) and ciprofloxacin (48.45% vs 21.90%) was decreased (P<0.001), while the resistance rate to levofloxacin (45.74% vs 58.73%) and ciprofloxacin (46.90% vs 66.67%) was increased (P<0.001) after the breakpoints revision. The empirical usage rate of fluoroquinolones in patients infected with , , or was 20.94%, which was influenced by the breakpoint revision (P=0.022), age (P=0.007), and the department (P=0.006); the appropriateness rate was 28.74%, affected by the pathogenic bacteria (P=0.001) and multidrug-resistant microorganism (P=0.001), department (P=0.024), and the length of stay before the empirical therapy (P=0.016).

Conclusion: The susceptibility of bacteria to antibiotics has changed significantly after the breakpoint revision while the clinicians' empirical therapy failure to change accordingly, which results in the decrease of the appropriateness of empirical use. It is enlightened that we should conduct more research to evaluate the rational use of antibiotics from the laboratory perspective and carry out interventions such as education and supervision to strengthen the collaboration between the microbiology laboratories and clinicians to improve the empirical antibiotic therapy and slow down the antimicrobial resistance.
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http://dx.doi.org/10.2147/IDR.S329477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418362PMC
August 2021

Improved Survival over Time After Resection of Colorectal Liver Metastases and Clinical Impact of Multigene Alteration Testing in Patients with Metastatic Colorectal Cancer.

J Gastrointest Surg 2021 Sep 10. Epub 2021 Sep 10.

Departments of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX, USA.

Background: The past 20 years have seen advances in colorectal cancer management. We sought to determine whether survival in patients undergoing resection of colorectal liver metastases (CLM) has improved in association with three landmark advances: introduction of irinotecan- and/or oxaliplatin-containing regimens, molecular targeted therapy, and multigene alteration testing.

Methods: Patients undergoing CLM resection during 1998-2014 were identified and grouped by resection year. The influence of alterations in RAS, TP53, and SMAD4 was evaluated and validated in an external cohort including patients with unresectable metastatic colorectal cancer.

Results: Of 1961 patients, 1599 met the inclusion criteria. Irinotecan- and/or oxaliplatin-containing regimens and molecular targeted therapy were used for more than 50% of patients starting in 2001 and starting in 2006, respectively, so patients were grouped as undergoing resection during 1998-2000, 2001-2005, or 2006-2014. Liver resectability indications expanded over time. The 5-year overall survival (OS) rate was significantly better in 2006-2014, vs. 2001-2005 (56.5% vs. 44.1%, P < 0.001). RAS alteration was associated with worse 5-year OS than RAS wild-type (44.8% vs. 63.3%, P < 0.001). However, OS did not differ significantly between patients with RAS alteration and wild-type TP53 and SMAD4 and patients with RAS wild-type in our cohort (P = 0.899) or the external cohort (P = 0.932). Of 312 patients with genetic sequencing data, 178 (57.1%) had clinically actionable alterations.

Conclusion: OS after CLM resection has improved with advances in medical therapy and surgical technique. Multigene alteration testing is useful for prognostication and identification of potential therapeutic targets.
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http://dx.doi.org/10.1007/s11605-021-05110-1DOI Listing
September 2021

Macrophage HIF-2α suppresses NLRP3 inflammasome activation and alleviates insulin resistance.

Cell Rep 2021 Aug;36(8):109607

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, China; Center for Obesity and Metabolic Disease Research, School of Basic Medical Sciences, Peking University, Beijing 100191, China; Center of Basic Medical Research, Institute of Medical Innovation and Research, Third Hospital, Peking University, Beijing, China. Electronic address:

The interrelation between hypoxia and immune response has pivotal roles in the pathogenesis of chronic metabolic diseases. However, the role of macrophage HIF-2α in NLRP3 inflammasome activation remains unclear. Here, we show that deficiency of HIF-2α in macrophages results in excessive activation of the NLRP3 inflammasome in a manner dependent on CPT1A-mediated enhancement of fatty acid oxidation (FAO). Mechanistically, HIF-2α binds directly to the Cpt1a promoter and is involved in the regulation of H3K27me3 methylation during NLRP3 inflammasome activation. Myeloid-specific Hif2α knockout mice exhibit exacerbated insulin resistance and increased activation of NLRP3 inflammasome in macrophages. Overexpression of the Hif2α gene or stabilization of the protein by FG-4592 ameliorates insulin resistance and reduces NLRP3 inflammasome activation in macrophages. Taken together, our results suggest that macrophage HIF-2α inhibits FAO-mediated activation of the NLRP3 inflammasome and alleviates insulin resistance.
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http://dx.doi.org/10.1016/j.celrep.2021.109607DOI Listing
August 2021

The correlation between chronic exposure to particulate matter and spontaneous abortion: A meta-analysis.

Chemosphere 2021 Aug 3;286(Pt 2):131802. Epub 2021 Aug 3.

Department of Toxicology, School of Public Health, Medical College of Soochow University, Suzhou, 215123, Jiangsu, China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, China. Electronic address:

Background: Spontaneous abortion (SAB) brings serious physical and psychological sequelae to women and their families. Though a growing body of individual studies have suggested the possible linkage between chronic particulate matter (PM) exposure and risks of SAB, the provided results were rather contradictory. We therefore performed an evidence-based meta-analysis.

Methods: We systematically searched the PubMed, EMBASE and Web of Science databases for available studies published before February 1, 2021 which reported associations between PM exposure and SAB. Corresponding models were applied to combine relative risks (RRs) and their confidence intervals (CIs) from eligible studies according to heterogeneity test. The GRADEpro app was used to evaluate the certainty of evidence. Sensitivity analyses and a publication bias assessment were also utilized to determine the stability of results.

Results: Of the initial 2358 citations, 6 papers examining the chronic effects of PM exposure were deemed eligible and a total population of approximately 723,000 was observed. Pooled RR for SAB risks associated with a 10 μg/m increase in fine particulate matter (PM) and particulate matter ≤ 10 μm in aerodynamic diameter (PM) were 1.20 (95%CI: 1.01-1.40) and 1.09 (95%CI: 1.02-1.15), respectively. The GRADE results of PM and PM were both categorized as "moderate" certainty evidence.

Conclusion: Our findings revealed a significant increase of SAB hazards related with maternal PM exposure, and this study may therefore provide new evidence for personal protection to improve reproductive health.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131802DOI Listing
August 2021

Final results of a phase 2 clinical trial of LCL161, an oral SMAC mimetic for patients with myelofibrosis.

Blood Adv 2021 08;5(16):3163-3173

Department of Leukemia.

Outcomes in patients with high-risk and treatment-resistant myelofibrosis (MF) post-JAK inhibitor therapy remain poor, with no approved drug therapies beyond the JAK inhibitor class. In certain clinical situations, such as severe thrombocytopenia, administration of most JAK inhibitors are contraindicated. Thus, there is an unmet medical need for the development of novel agents for patients with MF. SMAC mimetics [or inhibitor of apoptosis (IAP) antagonists] induce apoptosis in cancer cells. Because these agents are hypothesized to have increased activity in a tumor necrosis factor-α cytokine-rich microenvironment, as is the case with MF, we conducted a single-center, investigator-initiated phase 2 clinical trial, with a monovalent SMAC mimetic LCL161 (oral, starting dose, 1500 mg per week) in patients with intermediate to high-risk MF. In an older group, 66% with ≥2 prior therapies and a median baseline platelet count of 52 × 103/μL and 28% with ASXL1 mutations, we observed a 30% objective response by Revised International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) 2013 criteria. Notably, 6 responding patients achieved clinical improvement of anemia: 4, hemoglobin response; 2, transfusion independence. Median OS was 34 months (range, 2.2-60.1+). Reductions of cIAPs were observed in all responders. The most common toxicity was nausea/vomiting (N/V) in 64% (mostly grade 1/2); fatigue in 46%; and dizziness/vertigo in 30%. There were 4 grade 3/4 adverse events (2, syncope; 1, N/V; 1, skin eruption/pruritis). There were 2 deaths during the study period, both unrelated to the study drug. SMAC mimetics may represent an option for older patients with thrombocytopenia or for those in whom prior JAK inhibitors has failed. This trial was registered at www.clinicaltrials.gov as #NCT02098161.
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http://dx.doi.org/10.1182/bloodadvances.2020003829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405193PMC
August 2021

Characterization of the Human Oropharyngeal Microbiomes in SARS-CoV-2 Infection and Recovery Patients.

Adv Sci (Weinh) 2021 Aug 22:e2102785. Epub 2021 Aug 22.

Gene Hospital of Henan Province; Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.

Respiratory tract microbiome is closely related to respiratory tract infections, while characterization of oropharyngeal microbiome in recovered coronavirus disease 2019 (COVID-19) patients is not studied. Herein, oropharyngeal swabs are collected from confirmed cases (CCs) with COVID-19 (73 subjects), suspected cases (SCs) (36), confirmed cases who recovered (21), suspected cases who recovered (36), and healthy controls (Hs) (140) and then completed MiSeq sequencing. Oropharyngeal microbial α-diversity is markedly reduced in CCs versus Hs. Opportunistic pathogens are increased, while butyrate-producing genera are decreased in CCs versus Hs. The classifier based on eight optimal microbial markers is constructed through a random forest model and reached great diagnostic efficacy in both discovery and validation cohorts. Notably, the classifier successfully diagnosed SCs with positive IgG antibody as CCs and is demonstrated from the perspective of the microbiome. Importantly, several genera with significant differences gradually increase and decrease along with recovery from COVID-19. Forty-four oropharyngeal operational taxonomy units (OTUs) are closely correlated with 11 clinical indicators of SARS-CoV-2 infection and Hs based on Spearman correlation analysis. Together, this research is the first to characterize oropharyngeal microbiota in recovered COVID-19 cases and suspected cases, to successfully construct and validate the diagnostic model for COVID-19 and to depict the correlations between microbial OTUs and clinical indicators.
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http://dx.doi.org/10.1002/advs.202102785DOI Listing
August 2021

Effects of Regulation on Carbapenem Prescription in a Large Teaching Hospital in China: An Interrupted Time Series Analysis, 2016-2018.

Infect Drug Resist 2021 11;14:3099-3108. Epub 2021 Aug 11.

First Affiliated Hospital, School of Medicine, Shihezi University, Xinjiang, Shihezi, People's Republic of China.

Purpose: Carbapenem resistance due to the overuse of carbapenems has become a public health problem worldwide, particularly in low- and middle-income countries (LMICs). However, there are few policies guiding carbapenem prescription, and their effectiveness is still unclear. A regulation targeting carbapenem prescription was implemented in March 2017 in China. This study aimed to assess the effects of the regulation for providing evidence on the prudent use of carbapenems.

Patients And Methods: This was an interventional, retrospective study started in January 2017. The intervention covered establishing performance appraisal indicators, special authorisation, strict prescribing restrictions, and dedicated supervision, particularly in the intensive care unit (ICU). Data on adult inpatients who received at least one carbapenems were extracted from January 2016 to December 2018. Segmented regression analysis was performed to evaluate the effect of the regulation.

Results: A total of 2005 inpatients received carbapenems. Segmented regression models showed an immediate decline in the intensity of antibiotic consumption (IAC) of carbapenems (coefficient = -9.65, p < 0.001), particularly imipenem (coefficient = -6.82, p = 0.002), and the antibiotic consumption of carbapenems (coefficient = -133.60, p = 0.003) in the ICU. And there is a decreasing trend in the IAC of meropenem (coefficient = -0.03, = 0.008) in all departments. Furthermore, the IAC of carbapenems and imipenem (coefficient = -0.36, = 0.035; coefficient = -0.49, = 0.025, respectively), and the average length of stay (ALoS) (coefficient = -0.73, < 0.001) showed downward trends in the ICU.

Conclusion: The intervention effectively reduced the IAC of carbapenems and imipenem, carbapenem consumption and the ALoS in the ICU, and the IAC of meropenem in all departments. The effects of the intervention were significant in the ICU, which indicated an urgent need for stronger regulations focusing on critical departments in the future.
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http://dx.doi.org/10.2147/IDR.S322938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364849PMC
August 2021

Case Report: Improved Height in a Patient With Myhre Syndrome Using a Combination of Growth Hormone and Letrozole.

Front Pediatr 2021 29;9:675934. Epub 2021 Jul 29.

Department of Pediatrics, Peking University Health Science Center, Peking University Third Hospital, Beijing, China.

Myhre syndrome is a rare disorder caused by a heterozygous mutation in the gene. Affected patients may exhibit dysmorphic facial features, intrauterine growth retardation, short stature, obesity, muscle hypertrophy, thickened skin, limited joint movement, hearing impairment, and varying degrees of psychomotor developmental disorder. Serious complications of the cardiovascular and respiratory system may be seen later in life. We report the case of a Chinese boy with Myhre syndrome presenting with a novel symptom of giant testicles where treatment with growth hormone combined with letrozole successfully improved his short stature. This case shows that letrozole combined with growth hormone can improve height in children with Myhre syndrome without adverse effects.
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http://dx.doi.org/10.3389/fped.2021.675934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360501PMC
July 2021

Expression pattern and regulatory effect of lysine-specific demethylase 2A gene in clear cell renal cell carcinoma.

BMC Urol 2021 Aug 14;21(1):108. Epub 2021 Aug 14.

Department of Ultrasound, The First Hospital of China Medical University, No. 155 NanjingBei Street, Heping District, Shenyang, 110001, Liaoning Province, People's Republic of China.

Background: Our study aimed to explore the expression and the biological role of lysine-specific demethylase 2A (KDM2A) in clear cell renal cell carcinoma (ccRCC).

Methods: In vitro, KDM2A expression was measured by qRT-PCR and western blot. A total of 50 patients with ccRCC were included, and KDM2A expression in ccRCC tissues was assessed by qRT-PCR and immunohistochemistry. The effects of KDM2A expression on cell biological behavior were examined by cell counting kit-8 assay, transwell assay and flow cytometry, respectively. The prognostic value of KDM2A in ccRCC was evaluated by Kaplan-Meier method.

Results: The KDM2A expression was significantly upregulated in ccRCC cell line (P < 0.05). Compared with para cancer tissues, ccRCC samples showed a higher KMD2A mRNA level and a larger proportion of high KDM2A expression (all P < 0.05). High KDM2A mRNA expression was more likely to occur in ccRCC tissues with tumor size > 7 cm (P = 0.005) and T3-T4 stage (P = 0.047). Knockdown of KDM2A significantly suppressed the proliferation and invasion, and promoted the apoptosis of ccRCC cells (all P < 0.05). Moreover, Kaplan-Meier survival analysis revealed that higher level of KDM2A expression in ccRCC patients was associated with lower survival rate (P = 0.004).

Conclusions: Our findings demonstrated a vital role of KDM2A in the pathogenesis of ccRCC, which provides a new perspective to understand the underlying molecular mechanisms in ccRCC.
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http://dx.doi.org/10.1186/s12894-021-00867-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364110PMC
August 2021

GaOOH-modified metal-organic frameworks UiO-66-NH: Selective and sensitive sensing four heavy-metal ions in real wastewater by electrochemical method.

Talanta 2021 Nov 3;234:122679. Epub 2021 Jul 3.

Key Laboratory of Bioelectrochemistry & Environmental Analysis of Gansu Province, College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou, 730070, PR China.

Heavy metal pollution in the environment poses a serious threat to the ecosystem and human health, which has attracted widespread attention. In this study, an octahedral structure composite composed of UiO-66-NH MOFs and semiconductor GaOOH materials has been prepared and used as electrode materials successfully. These composites can be used for the real-time and online determination of Cd, Cu, Hg, and Pb in real water samples simultaneously or alone via an electrochemical method. Zr-MOF has a large and unique surface area that is beneficial to the adsorption and preconcentration of heavy metal ions. The experiment parameters such as pH, deposition potential, and deposition time were optimized. Under the optimized conditions, the electrochemical performances and practical applications of Zr-MOF composites modified electrode have been investigated, which shows excellent wider linear range and lower detection limit (LOD). The results demonstrated excellent selectivity, reproducibility, stability and applicability for the detection of four metal ions. These superior features stem from the synergistic reaction mechanism of UiO-66-NH and GaOOH. In addition, it has been established a new detection strategy for heavy metal ions through the form of metal-organic framework (MOF) composite in this work. It may provide a novel platform for the quantitative determination of heavy metal ions in various environmental samples.
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http://dx.doi.org/10.1016/j.talanta.2021.122679DOI Listing
November 2021

Influence of Baseline Positron Emission Tomography in Metastatic Gastroesophageal Cancer on Survival and Response to Therapy.

Oncology 2021 Aug 5:1-6. Epub 2021 Aug 5.

Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Background: The value of baseline fluorodeoxyglucose-positron emission tomography-computed tomography (PET-CT) remains uncertain once gastroesophageal cancer is metastatic. We hypothesized that assessment of detailed PET-CT parameters (maximum standardized uptake value [SUVmax] and/or total lesion glycolysis [TLG]), and the extent of metastatic burden could aid prediction of probability of response or prognosticate.

Methods: We retrospectively analyzed treatment-naive patients with stage 4 gastroesophageal cancer (December 2002-August 2017) who had initial PET-CT for cancer staging at MD Anderson Cancer Center. SUVmax and TLG were compared with treatment outcomes for the full cohort and subgroups based on metastatic burden (≤2 or >2 metastatic sites).

Results: We identified 129 patients with metastatic gastroesophageal cancer who underwent PET-CT before first-line therapy. The median follow-up time was 61 months. The median overall survival (OS) was 18.5 months; the first progression-free survival (PFS) was 5.5 months. SUVmax or TLG of the primary tumor or of all metastases combined had no influence on OS or PFS, whether the number of metastases was ≤2 or >2. Overall response rates (ORRs) to first-line therapy were 48% and 45% for patients with ≤2 and >2 metastases, respectively (nonsignificant). ORR did not differ based on low or high values of SUVmax or TLG.

Conclusions: This is the first assessment of a unique set of PET-CT data and its association with outcomes in metastatic gastroesophageal cancer. In our large cohort of patients, detailed analyses of PET-CT (by SUVmax and/or TLG) did not discriminate any parameters examined. Thus, baseline PET-CT in untreated metastatic gastroesophageal cancer patients has limited or no utility.
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http://dx.doi.org/10.1159/000517842DOI Listing
August 2021

Effects of low lead exposure on sperm quality and sperm DNA methylation in adult men.

Cell Biosci 2021 Jul 30;11(1):150. Epub 2021 Jul 30.

NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University, Shanghai, China.

Instruction: Lead (Pb) exposure is a risk factor for male infertility, but the epigenetic changes in sperm DNAattributable to lead exposure is poorly defined.

Methods: In this study, we investigated whether low Pb exposure (<  10 µg/dL) affects the sperm quality. Blood, urine, and semen samples of 297 men of childbearing age were analyzed for all relevant parameters. Based on the blood Pb level (BLL), participants were allocated to RL (0-2.5 µg/dL), RM (2.5-5 µg/dL), and RH (5-10 µg/dL) groups. The 5-methylcytosine and 5-hydroxymethylcytosine patterns in the sperm DNA were identified using methylated DNA immunoprecipitation and hydroxymethylated DNA immunoprecipitation sequencing.

Results: The non-progressive motility (NP) was significantly increased and associated with global hypomethylation of sperm DNA in the RH group compared with the RL group, indicating that aberrant sperm methylation due to low Pb exposure is possibly associated with reduced sperm motility. The hypomethylated promoter regions were primarily enriched in the calcium (Ca) homeostasis pathway. Further, the interaction between Ca and Pb was associated with sperm rapid progressive motility and asthenospermia risk, although no significant methylation abnormality was observed in those with BLL  <  5 µg/dL. When BLL was  >  5 µg/dL or when predicting NP, no significant Pb-Ca interaction was observed.

Discussion: Overall, our results indicate that aberrant DNA methylation of the Ca homeostasis pathway, induced by low Pb exposure, is the potential cause for reduced sperm velocity.
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http://dx.doi.org/10.1186/s13578-021-00665-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8335892PMC
July 2021

Temperature and time-controlled hydrothermal growth and sorption selectivity of titania nanowires on titanium fiber for highly efficient solid-phase microextraction.

J Chromatogr A 2021 Sep 22;1653:462400. Epub 2021 Jul 22.

College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou 730070, China; Key Lab of Bioelectrochemistry & Environmental Analysis of Gansu, Lanzhou 730070, China. Electronic address:

Two kinds of TiO nanowires (TiONWs) with different orientation were in-situ grown on Ti substrates by controlling temperature and time during the hydrothermal process. The adsorption performance was evaluated by using typical aromatic compounds as model analytes coupled to HPLC with UV detection. The results demonstrated that the TiONWs coating grown at higher temperature within longer time had better affinity towards PAHs. For this purpose, the key experimental factors affecting the adsorption performance of the TiONWs coating fabricated at 200 °C for 10 h were further investigated and optimized for the extraction of PAHs. Under the optimized conditions, the proposed method presented linear responses in the concentration ranges of 0.05 to 200 μg·L PAHs with correlation coefficients more than 0.998. LODs (S/N=3) were 0.008 to 0.034 μg·L. Moreover, RSDs for the single fiber repeatability of the intra-day and the inter-day analyses were less than 5.6% (n=5) and 5.8%, respectively. RSDs for the fiber-to-fiber reproducibility were between 5.1% and 6.5%. Finally, the proposed method was successfully applied to the selective preconcentration and determination of trace PAHs in environmental water samples. In addition, The fabricated Ti fiber can be used at least 200 times due to its high mechanical and chemical stability.
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http://dx.doi.org/10.1016/j.chroma.2021.462400DOI Listing
September 2021

Intestinal hypoxia-inducible factor 2α regulates lactate levels to shape the gut microbiome and alter thermogenesis.

Cell Metab 2021 Jul 26. Epub 2021 Jul 26.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, and the Key Laboratory of Molecular Cardiovascular Science (Peking University), Ministry of Education, Beijing, China; Center of Basic Medical Research, Institute of Medical Innovation and Research, Third Hospital, Peking University, Beijing, China; Center for Obesity and Metabolic Disease Research, School of Basic Medical Sciences, Peking University, Beijing, China. Electronic address:

Accumulating evidence suggests that the gut microbiota regulates obesity through metabolite-host interactions. However, the mechanisms underlying such interactions have been unclear. Here, we found that intestinal hypoxia-inducible factor 2α (HIF-2α) positively regulates gut lactate by controlling the expression of intestinal Ldha. Intestine-specific HIF-2α ablation in mice resulted in lower lactate levels, and less Bacteroides vulgatus and greater Ruminococcus torques abundance, respectively. Together, these changes resulted in elevated taurine-conjugated cholic acid (TCA) and deoxycholic acid (DCA) levels and activation of the adipose G-protein-coupled bile acid receptor, GPBAR1 (TGR5). This activation upregulated expression of uncoupling protein (UCP) 1 and mitochondrial creatine kinase (CKMT) 2, resulting in elevation of white adipose tissue thermogenesis. Administration of TCA and DCA mirrored these phenotypes, and colonization with B. vulgatus and R. torques inhibited and induced thermogenesis, respectively. This work deepens our understanding of how host genes regulate the microbiome and provides novel strategies for alleviating obesity.
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http://dx.doi.org/10.1016/j.cmet.2021.07.007DOI Listing
July 2021

Real-time confocal microscopy imaging of corneal cytoarchitectural changes induced by different stresses.

Exp Eye Res 2021 Sep 26;210:108706. Epub 2021 Jul 26.

Eye Institute & Affiliated Xiamen Eye Center, School of Pharmaceutical Sciences & School of Medicine, Xiamen University, Xiamen, China; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, China. Electronic address:

Maintenance of the corneal refractive power and tissue transparency is essential for normal vision. Real-time characterization of changes in corneal cells during suffering stresses or wound healing may provide a way to identify novel targets, whose therapeutic manipulation can improve the outcome of this response induced by injury. Here we describe a novel user friendly and effective confocal real-time confocal microscopy attachment that monitors the effects of anisoosmotic stress on cell morphology and corneal thickness in situ. Corneal epithelial nuclei gradually became highly reflective in the isotonic group and the corneal stroma was slightly thickened as compared with that seen prior to 60 min exposure to a hypotonic solution. After 30 min of exposure to hypertonic stress, the corneal stromal cells became crenate and shriveled. The hyper-reflective area of the corneal stroma in the hypo-osmotic group was significantly larger than that in the other two groups, as demonstrated by 3D reconstruction imaging. The hypotonic fresh chlorinated pool water was observed to cause atrophy of corneal epithelial nuclei, while the isosmotic bee venom solution caused high reflection of the corneal stroma layer and corneal endothelial cell damage. With the microscopic attachment, the inward movement of corneal epithelial cells toward the denuded central region was detected in the serum-treated group. The microscopy attachment is an effective system for obtaining a more detailed understanding of the time dependent losses in the corneal cell structure and tissue architecture of full thickness corneas induced by osmotic stress or cytotoxic agents.
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http://dx.doi.org/10.1016/j.exer.2021.108706DOI Listing
September 2021

Aorta-specific DNA methylation patterns in cell-free DNA from patients with bicuspid aortic valve-associated aortopathy.

Clin Epigenetics 2021 Jul 28;13(1):147. Epub 2021 Jul 28.

Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

Background: The dilation of the aorta that occurs as a consequence of a congenitally bicuspid aortic valve (BAV) is associated with a risk of dissection, aneurysm or rupture. With progressive aortopathy, surgery is often recommended, but current patient selection strategies have limitations. A blood-based assay to identify those who would most benefit from prophylactic surgery would be an important medical advance. In a proof-of-concept study, we sought to identify aorta-specific differentially methylated regions (DMRs) detectable in plasma cell-free DNA (cfDNA) obtained from patients undergoing surgery for BAV-associated aortopathy.

Methods: We used bioinformatics and publicly available human methylomes to identify aorta-specific DMRs. We used data from 4D-flow cardiac magnetic resonance imaging to identify regions of elevated aortic wall shear stress (WSS) in patients with BAV-associated aortopathy undergoing surgery and correlated WSS regions with aortic tissue cell death assessed using TUNEL staining. Cell-free DNA was isolated from patient plasma, and levels of candidate DMRs were correlated with aortic diameter and aortic wall cell death.

Results: Aortic wall cell death was not associated with maximal aortic diameter but was significantly associated with elevated WSS. We identified 24 candidate aorta-specific DMRs and selected 4 for further study. A DMR on chromosome 11 was specific for the aorta and correlated significantly with aortic wall cell death. Plasma levels of total and aorta-specific cfDNA did not correlate with aortic diameter.

Conclusions: In a cohort of patients undergoing surgery for BAV-associated aortopathy, elevated WSS created by abnormal flow hemodynamics was associated with increased aortic wall cell death which supports the use of aorta-specific cfDNA as a potential tool to identify aortopathy and stratify patient risk.
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http://dx.doi.org/10.1186/s13148-021-01137-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320174PMC
July 2021

Improvement of a SARS-CoV-2 vaccine by enhancing the conjugation efficiency of the immunogen to self-assembled nanoparticles.

Cell Mol Immunol 2021 08 19;18(8):2042-2044. Epub 2021 Jul 19.

Institute of Human Virology, Key Laboratory of Tropical Disease Control of the Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agents and Immunotechnology, Engineering Research Center of Gene Vaccines of the Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, Guangdong, China.

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http://dx.doi.org/10.1038/s41423-021-00736-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287548PMC
August 2021

An observation approach in evaluation of ozone production to precursor changes during the COVID-19 lockdown.

Atmos Environ (1994) 2021 Oct 14;262:118618. Epub 2021 Jul 14.

Institute for Environmental and Climate Research, Jinan University, Guangzhou, 511443, China.

The increase of surface ozone during the Corona Virus Disease 2019 (COVID-19) lockdown in China has aroused great concern. In this study, we combine 1.5 years of measurements for ozone, volatile organic compounds (VOCs), and nitrogen oxide (NO) at four sites to investigate the effect of COVID-19 lockdown on surface ozone in Dongguan, an industrial city in southern China. We show that the average concentrations of NO and VOCs decreased by 70%-77% and 54%-68% during the lockdown compared to pre-lockdown, respectively. Based on the source apportionment of VOCs, the contribution of industrial solvent use reduced significantly (86%-94%) during the lockdown, and climbed back slowly along with the re-opening of the industry after lockdown. A slight increase in mean ozone concentration (3%-14%) was observed during the lockdown. The rise of ozone was the combined effect of substantial increase at night (58%-91%) and small reduction in the daytime (1%-17%). These conflicting observations in ozone response between day and night to emission change call for a more detailed approach to diagnostic ozone production response with precursor changes, rather than directly comparing absolute concentrations. We propose that the ratio of daily Ox (i.e. ozone + NO) enhancement to solar radiation can provide a diagnostic parameter for ozone production response during the lockdown period. Smaller ratio of daily O (ozone + NO) enhancement to solar radiation during the lockdown were observed from the long-term measurements in Dongguan, suggesting significantly weakened photochemistry during the lockdown successfully reduces local ozone production. Our proposed approach can provide an evaluation of ozone production response to precursor changes from restrictions of social activities during COVID-19 epidemic and also other regional air quality abatement measures (e.g. public mega-events) around the globe.
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http://dx.doi.org/10.1016/j.atmosenv.2021.118618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277545PMC
October 2021

Healthcare workers' behaviors on infection prevention and control and their determinants during the COVID-19 pandemic: a cross-sectional study based on the theoretical domains framework in Wuhan, China.

Arch Public Health 2021 Jun 30;79(1):118. Epub 2021 Jun 30.

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095, Jiefang Avenue, Wuhan, 430030, Hubei Province, China.

Background: Infection prevention and control (IPC) measures are crucial to combat the COVID-19 pandemic. This study aimed to explore the levels and determinants of HCWs' IPC behaviors based on the theoretical domains framework (TDF), which has been shown to be effective in guiding behavior change.

Methods: A cross-sectional survey was conducted in Wuhan, China in January 2020. Self-reported hand hygiene and droplet isolation behaviors (including the use of masks, gloves, goggles and gowns) were set as dependent variables. TDF domains and HCWs' characteristics were independent variables. Negative binomial regression analyses were performed to explore their relationships.

Results: HCWs reported good IPC behaviors, while the compliance with goggle and gown use was relatively low (below 85%). Environmental context and resources domain was significantly related to hand hygiene (β = 0.018, p = 0.026), overall droplet isolation behaviors (β = 0.056, p = 0.001), goggle (β = 0.098, p = 0.001) and gown use (β = 0.101. p < 0.001). Knowledge domain was significantly related to goggle (β = 0.081, p = 0.005) and gown use (β = 0.053, p = 0.013). Emotion domain was a predictor of overall droplet isolation behaviors (β = 0.043, p = 0.016), goggle (β = 0.074, p = 0.026) and gown use (β = 0.106, p < 0.001). Social influences domain was a predictor of overall droplet isolation behaviors (β = 0.031, p = 0.029) and gown use (β = 0.039, p = 0.035). HCWs in high-risk departments had better behaviors of gown use (β = 0.158, p = 0.032). HCWs who had encountered confirmed or suspected patients reported worse behaviors of goggle (β = - 0.127, p = 0.050) and gown use (β = - 0.153, p = 0.003).

Conclusions: Adequate personal protective materials and human resources, education and training, as well as supervision and role model setting are necessary to improve IPC behaviors regarding the COVID-19 pandemic.
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http://dx.doi.org/10.1186/s13690-021-00641-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242273PMC
June 2021

Trajectories of Function and Symptom Change in Desvenlafaxine Clinical Trials: Toward Personalized Treatment for Depression.

J Clin Psychopharmacol 2021 Sep-Oct 01;41(5):579-584

Department of Psychiatry, Columbia University College of Physicians and Surgeons and New York State Psychiatric Institute, New York, NY.

Purpose/background: Heterogeneity has been documented in trajectories of symptom change during antidepressant treatment for major depressive disorder (MDD). It is unclear whether distinct trajectories of change exist for functioning during antidepressant treatment.

Methods/procedures: This analysis explored distinct trajectories of functioning in MDD and tested whether they corresponded to trajectories of symptom change. Data were from 4317 patients and were pooled from 9 randomized placebo-controlled trials. Growth mixture modeling was used to identify trajectories of Hamilton Rating Scale for Depression (HRSD) and Sheehan Disability Scale (SDS) for placebo- and desvenlafaxine-treated patients.

Findings/results: Three trajectories were identified for symptoms (HRSD) in patients receiving placebo (mean reduction baseline to week 8, -18.4 [most favorable] to -2.6 points [least favorable]). Four HRSD trajectories were identified for patients receiving desvenlafaxine (mean reduction from baseline to week 8, -17.2 [most favorable] to -2.6 points [least favorable]). Four trajectories were identified for functioning (SDS) in patients receiving placebo (mean reduction baseline to week 8, -13.6 [most favorable] to -0.8 points [least favorable]), and 3 for desvenlafaxine (-12.8 to -1.4 points, respectively). Percentages of agreement between most favorable HRSD and SDS trajectories were 75% (placebo) and 85% (desvenlafaxine), and for least favorable trajectories were 88% (placebo) and 80% (desvenlafaxine).

Implications/conclusions: Distinct trajectories of change based on symptoms and functioning were identified among patients with MDD receiving desvenlafaxine and among patients with MDD receiving placebo. Differentiating subpopulations of patients has the potential to provide a more personalized treatment of patients with MDD.ClinicalTrials.govIdentifiers: NCT00072774; NCT00277823; NCT00300378; NCT00384033; NCT00798707; NCT00863798; NCT01121484; NCT00824291; NCT01432457.
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http://dx.doi.org/10.1097/JCP.0000000000001435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407446PMC
June 2021

Regional modeling of secondary organic aerosol formation over eastern China: The impact of uptake coefficients of dicarbonyls and semivolatile process of primary organic aerosol.

Sci Total Environ 2021 Nov 5;793:148176. Epub 2021 Jun 5.

Guangdong Province Key Laboratory for Climate Change and Natural Disaster Studies, School of Atmospheric Sciences, Sun Yat-sen University, Guangzhou 510275, China.

Capturing the secondary organic aerosol (SOA) concentration using the chemical transport model is difficult due to a large knowledge gap of its formation mechanism. Previous studies demonstrated the uptake of dicarbonyls and semivolatile process of primary organic aerosol (POA) emissions are the significant sources of SOA. However, the uptake coefficients of dicarbonyls have large uncertainties and the SOA from the semivolatile process of POA emission remains unclear. We applied the revised reactive uptake parameterization, with "salting effects" for dicarbonyls, and updated approaches for POA to the Community Multiscale Air Quality Modeling System (CMAQ) simulations for October 2014 to study their impacts on modeling the SOA formation over eastern China. We introduce a method of quantifying crystalized or deliquescent aerosols to further improve the parameterization. The revised glyoxal uptake coefficients results in higher glyoxal SOA in the Beijing-Tianjin-Hebei region, where is typically under low relative humidity (RH) and high aerosol pH conditions. It gives lower glyoxal SOA in the Pearl River Delta region, where is typically under high RH and low pH conditions. The updated parameterization gives negligible methylglyoxal SOA due to the low uptake coefficients. The implementation of semivolatile process of POA and the approach for potential SOA from combustion sources will largely decrease the predicted POA and increase the modeled SOA concentrations over eastern China. The increased SOA from POA emissions could improve the model performance for organic carbon and SOA. It slightly improves the performance in PM modeling by compensating the reduction of modeled POA. This study indicates the mixed impact of a parameterization considering "salting effects" on modeling the dicarbonyls SOA in key regions of eastern China. It also demonstrates the improved performance by implementing the POA approaches in aerosol modeling using CMAQ. Meanwhile, the uncertainty in the revised reactive uptake parameterization and POA approaches is discussed.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148176DOI Listing
November 2021

Improved electrochemical performances by Ni-catecholate-based metal organic framework grown on NiCoAl-layered double hydroxide/multi-wall carbon nanotubes as cathode catalyst in microbial fuel cells.

Bioresour Technol 2021 Oct 19;337:125430. Epub 2021 Jun 19.

Department of Environmental Science, School of Life Science, Qufu Normal University, Qufu 273165, PR China.

In this study, a simple two-step hydrothermal method was used to prepare the cathode catalyst of the microbial fuel cell (MFC). NiCoAl- layered double hydroxide (LDH) nanosheets were grown vertically on multi-wall carbon nanotubes (MWCNTs) in situ; Ni-catecholate-based metal organic framework (Ni-CAT MOF) were modified on the surface of the nanosheets. The maximum output voltage of Ni-CAT/NiCoAl-LDH/MWCNTs was 475 mV, the maximum stabilization time was 8 d, the maximum output power was 448.5 ± 12.0 mW/m, which was 1.03 times that of NiCoAl-LDH/MWCNT-MFC (433.5 ± 14.8 mW/m) and 1.35 times of NiCoAl-LDH- MFC (329.9 ± 2.9 mW/m). The layer structure of LDH, conductivity of Ni-CAT and MWCNT improved the flow efficiency of ions between layers and effectively reduced transmission resistance, and these have effectively enhanced the cycle stability and power generation efficiency of the electrode.
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http://dx.doi.org/10.1016/j.biortech.2021.125430DOI Listing
October 2021

Quantifying the role of PM dropping in variations of ground-level ozone: Inter-comparison between Beijing and Los Angeles.

Sci Total Environ 2021 Sep 18;788:147712. Epub 2021 May 18.

College of Environmental Sciences and Engineering, Peking University, Beijing, China.

In recent decade the ambient fine particle (PM) levels have shown a trend of distinct dropping in China, while ground-level ozone concentrations have been increasing in Beijing and many other Chinese mega-cities. The variation pattern in Los Angeles was markedly different, with PM and ozone decreasing together over past decades. In this study, we utilize observation-based methods to establish the parametric relationship between PM concentration and key aerosol physical properties (including aerosol optical depth and aerosol surface concentration), and an observation-based 1-D photochemical model to quantify the response of PM decline in enhancing ground-level ozone pollution over a large PM concentration range (10-120 μg m). We find that the significance of ozone enhancement due to PM dropping depends on both the PM levels and optical properties of particles. Ozone formation increased by 37% in 2006-2016 due to PM dropping in Beijing, while it becomes less important (7%) as PM reaches below 40 μg/m, similar to Los Angeles since 1980s. Therefore, the two cities show the convergence of air pollutant characteristics. Hence a control strategy prioritizing reactive volatile organic compound abatement is projected to yield simultaneous ozone and PM reductions in Beijing, as experienced in Los Angeles.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147712DOI Listing
September 2021

Ibrutinib Plus Venetoclax for First-line Treatment of Chronic Lymphocytic Leukemia: A Nonrandomized Phase 2 Trial.

JAMA Oncol 2021 Aug;7(8):1213-1219

Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston.

Importance: Oral targeted therapies have advanced the treatment of chronic lymphocytic leukemia (CLL). These therapies include Bruton tyrosine kinase inhibitors, used as monotherapy, and the Bcl-2 inhibitor venetoclax, typically combined with the CD20 monoclonal antibody. Preclinical studies have shown synergy between Bruton tyrosine kinase inhibitors and the Bcl-2 inhibitor venetoclax.

Objective: To examine the rate of complete remission, complete remission with incomplete count recovery, and bone marrow-undetectable measurable residual disease (U-MRD) after treatment with the combination of ibrutinib and venetoclax.

Design, Setting, And Participants: A single-center, phase 2 nonrandomized trial enrolled patients from August 17, 2016, to June 5, 2018. Participants included previously untreated patients with CLL who met International Workshop on CLL 2008 criteria for treatment indication. Patients were required to have at least 1 of the following features: del(17p), TP53-mutated CLL, del(11q), unmutated immunoglobulin heavy-chain variable gene, or age 65 years or older.

Interventions: Therapy consisted of ibrutinib, 420 mg/d, monotherapy for 3 cycles, thereafter combined with venetoclax (standard weekly dose ramp-up to 400 mg/d) for a total of 24 cycles of combination treatment. Responses were assessed at serial points according to International Workshop on CLL 2008 criteria. Measurable residual disease (MRD) was assessed by multicolor flow cytometry with a sensitivity of 10-4.

Main Outcomes And Measures: Outcomes included complete remission, complete remission with incomplete count recovery, and bone marrow U-MRD rate.

Results: Eighty patients (57 [71%] men) were treated; median age was 65 years (range, 26-83 years). The median follow-up for all 80 patients was 38.5 months (range, 5.6-51.1 months). Five patients discontinued the study during the ibrutinib monotherapy phase; the remaining 75 patients received combination therapy. On an intent-to-treat analysis of combined treatment, 45 (56%) patients achieved bone marrow U-MRD remission at 12 cycles and 53 (66%) patients achieved bone marrow U-MRD remission at 24 cycles. Overall, 60 (75%) patients achieved bone marrow U-MRD remission as their best response. Responses were seen across all high-risk subgroups, independent of the immunoglobulin heavy-chain variable gene mutation status, fluorescence in situ hybridization category, or TP53 mutation. The 3-year progression-free survival was 93%, and 3-year overall survival was 96%. No patient had CLL progression; 2 patients developed Richter transformation.

Conclusions And Relevance: The findings of this study suggest that combination therapy with ibrutinib and venetoclax might be beneficial for previously untreated patients with CLL. Remissions appeared to be durable during a follow-up of more than 3 years, with activity seen across high-risk disease subgroups, including those with del(17p)/TP53-mutated CLL.

Trial Registration: ClinicalTrials.gov Identifier: NCT02756897.
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http://dx.doi.org/10.1001/jamaoncol.2021.1649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193546PMC
August 2021

Enhanced Thermoelectric and Mechanical Performances in Sintered BiSbTe-AgSbSe Composite.

ACS Appl Mater Interfaces 2021 Jun 20;13(21):24937-24944. Epub 2021 May 20.

Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201, China.

Bismuth telluride alloys have dominated the industrial application of thermoelectric cooling, but the relatively poor mechanical performance of commercial zone-melting material seriously limits the device integration and stability. Here, we exhibit synergistically enhanced thermoelectric and mechanical performances of sintered BiSbTe-AgSbSe composites. It is found that the increased hole concentration improves the σ to 40 μW cm K at room temperature, and the emerged various defects effectively suppress the to 0.57 W m K at 350 K. All effects harvest a highest = 1.2 at 350 K along with an average = 1.0 between 300-500 K in the = 0.2 sample. Notably, AgSbSe addition not only optimizes the thermoelectric properties, but also enhances the mechanical performance with a Vickers hardness of 0.75 GPa. Furthermore, the isotropy of thermoelectric properties is also observably promoted by solid-phase reaction combined with high-energy ball milling and hot pressing. Our study reveals a viable strategy to improve the comprehensive performance of sintered bismuth telluride materials.
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http://dx.doi.org/10.1021/acsami.1c05525DOI Listing
June 2021

The synthesis of novel fluorescent bimetal nanoclusters for aqueous mercury detection based on aggregation-induced quenching.

Anal Methods 2021 06 20;13(23):2575-2585. Epub 2021 May 20.

State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China.

In this research, new bimetal nanoclusters (DAMP-AuAg BNCs) with 4,6-diamino-2-mercaptopyrimidine (DAMP) as a reducing agent and stabilizer ligand were exploited. The nanoclusters displayed excellent fluorescent properties, very small size, good stability, and water solubility. It was found that the as-prepared DAMP-AuAg BNCs exhibited strong fluorescent emission at 640 nm under an excitation wavelength of 473 nm with a large Stokes shift of 167 nm, and the red fluorescence could be readily quenched with aqueous Hg. The DAMP-AuAg BNCs showed good specificity and sensitivity toward Hg in aqueous solution, and the fluorescence analysis of Hg showed a wide linear range from 0.85 μM to 246 μM and a detection limit of 20 nM. It is demonstrated that strong Hg-Au interactions led to the aggregation of nanoclusters, which caused the quenching of the fluorescence, and the affinity of Hg for nitrogen should also be considered. Due to the relevant good performance of DAMP-AuAg BNCs, they were applied to the fluorescence analysis of Hg in real water samples and were found to be a potential fluorescent sensor for aqueous mercury ions.
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http://dx.doi.org/10.1039/d1ay00342aDOI Listing
June 2021

Ibrutinib, fludarabine, cyclophosphamide, and obinutuzumab (iFCG) regimen for chronic lymphocytic leukemia (CLL) with mutated IGHV and without TP53 aberrations.

Leukemia 2021 May 18. Epub 2021 May 18.

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Chemoimmunotherapy with combined fludarabine, cyclophosphamide and rituximab (FCR) has been an effective treatment for patients with chronic lymphocytic leukemia (CLL). We initiated a phase II trial for previously untreated patients with CLL with mutated IGHV and absence of del(17p)/TP53 mutation. Patients received ibrutinib, fludarabine, cyclophosphamide, and obinutuzumab (iFCG) for three cycles. Patients who achieved complete remission (CR)/CR with incomplete count recvoery (CRi) with marrow undetectable measurable residual disease (U-MRD) received additional nine cycles of ibrutinib with three cycles of obinutuzumab; all others received nine additional cycles of ibrutinib and obinutuzumab. Patients in marrow U-MRD remission after cycle 12 discontinued all treatment, including ibrutinib. Forty-five patients were treated. The median follow-up is 41.3 months. Among the total 45 treated patients, after three cycles, 38% achieved CR/CRi and 87% achieved marrow U-MRD. After cycle 12, the corresponding numbers were 67% and 91%, respectively. Overall, 44/45 (98%) patients achieved marrow U-MRD as best response. No patient had CLL progression. The 3-year progression-free survival (PFS) and overall survival (OS) were 98% and 98%, respectively. Per trial design, all patients who completed cycle 12 discontinued ibrutinib, providing for a time-limited therapy. Grade 3-4 neutropenia and thrombocytopenia occurred in 58% and 40% patients, respectively. The iFCG regimen with only 3 cycles of chemotherapy is an effective, time-limited regimen for patients with CLL with mutated IGHV and without del(17p)/TP53 mutation.
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http://dx.doi.org/10.1038/s41375-021-01280-8DOI Listing
May 2021

Pollution evaluation and children's multimedia exposure of atmospheric arsenic deposition in the Pearl River Delta, China.

Sci Total Environ 2021 Sep 8;787:147629. Epub 2021 May 8.

Guangdong-Hongkong-Macau Joint Laboratory of Collaborative Innovation for Environmental Quality, Institute for Environmental and Climate Research, Jinan University, Guangzhou 510632, China. Electronic address:

The populous Pearl River Delta (PRD) region in China suffers from serious air arsenic (As) pollution. The objective of this study was to explore the pollution situation of atmospheric arsenic deposition in the PRD region, and to evaluate the associated multimedia daily intake in children. The average deposition flux was 3921.7 μg/m/year during the 2016-2017, and the pollution situation was even worse than that in 2015. A continuously increasing trend of arsenic atmospheric deposition was found. The bioaccessibility of As in the settled dust was determined as about 22% by a physiologically based extraction test (PBET). After corrected with the bioaccessibilities of As in the settled dust and food items, the geometry means (GM) value of daily uptake through multimedia ingestion of produce (dust and diet) originated from arsenic atmospheric deposition was 0.23 μg/kg/day for 1- to 6-year-old children. The contribution of the non-dietary oral exposure (settled dust) was negligible and just accounted for only 0.01% of the daily uptake. This estimated value was much lower than those in the literatures, in which the bioaccessibility of As was not taken into account, concluding that the role of the settled dust in the total daily intake may have been overestimated previously. Milk, eggs and freshwater fish were the dominant pathways for children to intake the products derived from atmospheric arsenic deposition. There still be a concern about the high non-carcinogenic and carcinogenic risk by long-term multimedia ingestion. Special care should be considered toward the emission sources of air arsenic, including the coal combustion from industries and construction dust, etc., to reduce the negative effect of air arsenic in children.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147629DOI Listing
September 2021

A multisite SNP genotyping and macrolide susceptibility gene method for based on MALDI-TOF MS.

iScience 2021 May 16;24(5):102447. Epub 2021 Apr 16.

National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, State Key Laboratory of Infectious Disease Prevention and Control, Beijing 102206, China.

In this study, a multisite SNP genotyping and macrolide (ML) susceptibility gene test method for () was developed based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The detection limit of this method for nucleic acids was 10 -10 copies/reaction. Six SNP site-based genotyping and 3 ML susceptibility sites could be detected simultaneously based on multiplex PCR and mass probe. Using the method constructed in this study, 141 Chinese clinical isolates were divided into 8 SNP types. All the SNP test results for the ML susceptibility gene were in line with those of the 23S rRNA sequencing results. With this method, the multisite SNP genotyping and ML susceptibility determination of can be completed simultaneously in one test, which greatly reduces the workload and cost, improves the genotyping ability of and deserves clinical application.
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http://dx.doi.org/10.1016/j.isci.2021.102447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105657PMC
May 2021

The impacts of background error covariance on particulate matter assimilation and forecast: An ideal case study with a modal aerosol model over China.

Sci Total Environ 2021 Sep 29;786:147417. Epub 2021 Apr 29.

Guangdong-Hong Kong-Macau Joint Laboratory of Collaborative Innovation for Environmental Quality, Guangzhou 510632, China; Institute for Environmental and Climate Research, Jinan University, Guangzhou 510632, China. Electronic address:

Accurate estimation of background error covariance (BEC) is the key to successful data assimilation (DA). In aerosol three-dimensional variational (3DVAR) DA, the National Meteorological Center (NMC) method is typically applied to estimate BEC, which uses the difference between forecasts of dissimilar lengths valid at the common time. The difference will be considerably small when the underestimation of the aerosol is caused by the lack of emissions or the missing of chemical progress, which makes the aerosol concentration field too difficult to constrain. In this study, a modified module for adjusting the BEC of individual aerosol species was developed in the Gridpoint Statistical Interpolation (GSI) 3DVAR system. This module was mainly utilized to expand the standard deviations and the horizontal length scales of BEC for the specified aerosol components by multiplying an adjustment factor. The results of the impacts of BEC on PM 24-hour forecast indicated that the horizontal length scales take a relatively more important role than the standard deviations. The horizontal length scales affect the influence sphere more significantly, which might be crucial for the longer length forecast. Moreover, the larger and the wider differences of the aerosol initial conditions produced by DA, the longer duration of DA benefits. Using the original BEC, the 24-hour forecast of PM reduced fractional error by 13%, while using the modified BEC in DA can decline fractional error by 29%. More work needs to be conducted to investigate how to modify the aerosol BEC in 3DVAR, or how to generate a suitable BEC, which is crucial for aerosol forecast and analysis, especially during the aerosol-polluted period.
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September 2021
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