Publications by authors named "Huifang Wang"

130 Publications

Fine mapping of a powdery mildew resistance gene MlIW39 derived from wild emmer wheat (Triticum turgidum ssp. dicoccoides).

Theor Appl Genet 2021 May 13. Epub 2021 May 13.

State Key Laboratory for Agrobiotechnology, Key Laboratory of Crop Heterosis and Utilization (MOE), Key Laboratory of Crop Genetic Improvement, China Agricultural University, Beijing, 100193, China.

Key Message: Powdery mildew resistance gene MlIW39, originated from wild emmer wheat accession IW39, was mapped to a 460.3 kb genomic interval on wheat chromosome arm 2BS. Wheat powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is destructive disease and a significant threat to wheat production globally. The most effective way to control this disease is genetic resistance. However, when resistance genes become widely deployed in agriculture, their effectiveness is compromised by virulent variants that were previously minor components of the pathogen population or that arise from mutation. This necessitates continual search for new sources of resistance in both wheat and its near relatives. In this study, we produced a common wheat line 8D49 (87-1/IW39//2*87-1), which has all-stage immunity to Bgt isolate E09 and many other Chinese Bgt isolates, by transferring powdery mildew resistance from Israeli wild emmer wheat (WEW) accession IW39 to the susceptible common wheat line 87-1. Genetic analysis indicated that the powdery mildew resistance in 8D49 was controlled by a single dominant gene, temporarily designated MlIW39. Genetic linkage analyses with molecular markers showed that MlIW39 was located in a 0.7 cm genetic region between markers QB-3-16 and 7Seq546 on the short arm of chromosome 2B. Fine mapping using three large F populations delimited MlIW39 to a physical interval of approximately 460.3 kb region in the WEW reference genome (Zavitan v1.0) that contained six annotated protein-coding genes, four of which had gene structures similar to known disease resistance genes. This provides a foundation for map-based cloning of MlIW39. Markers 7Seq622 and 7Seq727 co-segregating with MlIW39 can be utilized for marker-assisted selection in further genetic studies and wheat breeding.
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http://dx.doi.org/10.1007/s00122-021-03836-9DOI Listing
May 2021

Nomogram to predict survival outcome of patients with veno-arterial extracorporeal membrane oxygenation after refractory cardiogenic shock.

Postgrad Med 2021 May 4. Epub 2021 May 4.

The Second School of Clinical Medicine, Southern Medical University, Department of Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan 2nd Road, Guangzhou, Guangdong 510080, China.

Objective: This study aims to develop a nomogram model to predict the survival of refractory cardiogenic shock (RCS) patients that received veno-arterial extracorporeal membrane oxygenation (VA-ECMO).

Methods: A total of 235 and 209 RCS patients were supported with VA-ECMO from January 2018 to December 2019 in Guangdong Provincial People's Hospital, and from January 2020 to December 2020 in four third-grade and class-A hospitals were a development cohort (DC) and validation cohort (VC), respectively. Finally, 137 and 98 patients were included in the DC and VC. Multivariate logistic regression analysis was used to identify variables, and only these independent risk factors were used to establish the nomogram model. The receiver operating characteristic curve (ROC), calibration plot, decision curve, and clinical impact curves were used to evaluate the nomogram's discriminative ability, predictive accuracy, and clinical application value.

Results: Pre-ECMO cardiogenic arrest (pre-ECA), lactate (Lac), inotropic score (IS), and modified nutrition risk in the critically ill score (mNUTRIC score) were incorporated into the nomogram. This showed good discrimination in the DC, with an area under ROC (AUROC) and a 95% confidence interval (CI) of 0.959 (0.911-0.986). The AUROC (95% CI) of the VC was 0.928 (0.858-0.971). The calibration plots of the DC and VC presented good calibration results. The decision curve and clinical impact curve of the nomogram provided improved benefits for RCS patients.

Conclusions: This study established a prediction nomogram composed of pre-ECA, Lac, IS, and mNUTRIC scores that could help clinicians to predict the survival probability at hospital discharge precisely and rapidly for RCS patients that received VA-ECMO.
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http://dx.doi.org/10.1080/00325481.2021.1925562DOI Listing
May 2021

The Peculiar Clinical Symptoms and Treatment of Limbic Encephalitis Associated with AMPA Receptor Antibody.

Eur Neurol 2021 Apr 15:1-6. Epub 2021 Apr 15.

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

Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) antibody-related diseases are very rare in autoimmune neurological diseases. We collected and analyzed the data of 3 patients with peculiar clinical manifestation positive for AMPA2-R antibody in the Department of Neurology, Xuanwu Hospital, Capital Medical University. In our reported case series, 2 patients were male and 1 was female. The initial clinical features of 3 patients were all consistent with an encephalopathy predominantly involving the limbic system. Interestingly, as the disease continues to advance, case 1 presented with limb paralysis, case 2 developed typical cerebellar ataxia, and case 3 had symptoms of autonomic instability. These 3 types of clinical features were very rare in patients with AMPAR-Ab. After immunotherapy, cases 1 and 3 responded well and case 2 was not responsive. During the follow-up, residual memory loss of cases 1 and 3 improved gradually, and they returned to work. To eliminate the influence of the presence of other pathogenic antibodies, we analyzed the available individual clinical information of 37 patients with the single AMPAR-Ab by systematic literature review. A majority of patients had sudden short-term memory loss as the initial symptom and developed limbic encephalitis. Residual memory deficit was the most common symptom after discharge. The combination of at least 2 types of immunotherapy was recommended as the first-line treatment, and patients would benefit from the tumor screening. In addition, compared with the patients positive for single AMPAR-Ab, the patients with both AMPAR-Ab and other antibodies had a higher risk of malignant tumor and might have a poor therapeutic response, which led to a poor prognosis.
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http://dx.doi.org/10.1159/000515592DOI Listing
April 2021

Impact of socio-demographic co-variates on prognosis, tyrosine kinase-inhibitor use and outcomes in persons with newly-diagnosed chronic myeloid leukaemia.

J Cancer Res Clin Oncol 2021 Apr 9. Epub 2021 Apr 9.

National Clinical Research Center for Hematologic Disease, Peking University People's Hospital, Peking University Institute of Hematology, No. 11 Xizhimen South Street, Beijing, 100044, China.

Purpose: Define the impact of socio-demographic co-variates on outcomes of persons with newly-diagnosed chronic phase chronic myeloid leukaemia (CML).

Methods: Data of 961 consecutive subjects with newly-diagnosed CML were integrated for these outcomes in multi-variable Cox regression analyses after adjusting for confounders and interactions.

Results: Elder age was associated with less use of a 2nd generation TKI as initial therapy. Household registration, comorbidity(ies) and education level were associated with use of a generic rather than branded TKI as initial therapy. Subjects with lower education level were more likely to be diagnosed with CML because of leukaemia-related symptoms. Rural registration and lower education level were also associated with a greater likelihood of switching TKI-therapy. Lower education level was associated with lower likelihood of achieving MMR [HR = 0.8 (0.7, 0.9), p = 0.002], MR [HR = 0.8 (0.7, 1.0), p = 0.055], and poor FFS [HR = 1.7 (1.3, 2.5); p < 0.001], PFS [HR = 2.0 (1.1, 5.0); p = 0.014], CML-related survival [HR = 2.5 (1.0, 10.0); p = 0.060] and survival [HR = 2.5 (1.0, 10.0); p = 0.043]. Males had lower rates of MMR and MR and worse FFS, but not survival compared with females. Being married was associated with a higher rate of MR, fewer failures, progressions, and deaths.

Conclusion: Socio-demographic co-variates have a strong impact on therapy choice and responses in persons with newly-diagnosed CML, including circumstances of diagnosis, risk category and prognosis, use of initial TKI, switching TKIs, response to TKI-therapy, and outcomes.
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http://dx.doi.org/10.1007/s00432-021-03624-4DOI Listing
April 2021

[A Meta-analysis of risk factors related to the lymph nodes posterior to the right recurrent laryngeal nerve in thyroid micropapillary carcinoma].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2021 Mar;35(3):245-251

Department of Thyroid Surgery,the First Hospital of Shanxi Medical University.

To evaluate the risk factors for metastasis of the lymph nodes posterior to the right recurrent laryngeal nerve in thyroid micropapillary carcinoma(PTMC) by Meta-analysis. We searched domestic and foreign databases for relevant studies published up to June, 2020. Two independent reⅥewers performed literature screening and data extraction according to the inclusion and exclusion criteria. Then, Meta-analysis was performed using Revman 5.3 software. A total of 5 articles were included, with a total of 1884 subjects.The results of the study showed that the rate of lymph node metastasis in PTMC Ⅵb area was 10.8% (203/1884). The risk factors for metastasis included patients' age <45 years old, male, right lobe tumor Diameter ≥0.5 cm, invading the envelope, Ⅵa lymph node metastasis. Ⅵb lymph node dissection is recommended when there exists age<45 years, male sex, right lobe tumor≥0.5 cm, capsular invasion or Ⅵa lymph node metastasis.
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http://dx.doi.org/10.13201/j.issn.2096-7993.2021.03.012DOI Listing
March 2021

3D Cationic Polymeric Network Nanotrap for Efficient Collection of Perrhenate Anion from Wastewater.

Small 2021 Mar 21:e2007994. Epub 2021 Mar 21.

Department of Chemistry, University of North Texas, Denton, TX, 76201, USA.

Rhenium is one of the most valuable elements found in nature, and its capture and recycle are highly desirable for resource recovery. However, the effective and efficient collection of this material from industrial waste remains quite challenging. Herein, a tetraphenylmethane-based cationic polymeric network (CPN-tpm) nanotrap is designed, synthesized, and evaluated for ReO recovery. 3D building units are used to construct imidazolium salt-based polymers with positive charges, which yields a record maximum uptake capacity of 1133 mg g for ReO collection as well as fast kinetics ReO uptake. The sorption equilibrium is reached within 20 min and a k value of 8.5 × 10 mL g is obtained. The sorption capacity of CPN-tpm remains stable over a wide range of pH values and the removal efficiency exceeds 60% for pH levels below 2. Moreover, CPN-tpm exhibits good recyclability for at least five cycles of the sorption-desorption process. This work provides a new route for constructing a kind of new high-performance polymeric material for rhenium recovery and rhenium-contained industrial wastewater treatment.
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http://dx.doi.org/10.1002/smll.202007994DOI Listing
March 2021

Clinico-pathological features and mutational spectrum of 16 nemaline myopathy patients from a Chinese neuromuscular center.

Acta Neurol Belg 2021 Mar 19. Epub 2021 Mar 19.

Department of Neurology, the First Hospital of Shanxi Medical University, 85 Jiefang South Road, Taiyuan, 030001, China.

Nemaline myopathy (NM) is a congenital myopathy of great heterogeneity, characterized by the presence of rods in the cytoplasm of muscle fibers. The samples of 16 nemaline myopathy patients diagnosed by characteristically pathological features went through whole exon sequencing. Clinico-pathological and genetic features of the cases were systematically analyzed. According to the classification of nemaline myopathy by ENMC, 8 cases are typical congenital subtype, 6 cases are childhood/juvenile onset subtype and 2 case are adult onset subtype. In histological findings, characteristic purple-colored rods are discovered under modified gömöri trichrome staining (MGT). Electron microscopy revealed the presence of high electron-dense nemaline bodies around the submucosa and the nucleus nine patients (9/16 56.3%) were detected pathogenic causative mutations, among whom mutations in the NEB gene were the most frequent (6 patients, 66.7%). KBTBD13 gene mutation was discovered in two patients and ACTA1 gene mutation was discovered in 1 patient. Nemaline myopathy is a congenital myopathy with highly clinico-pathological and genetic heterogeneity. NEB gene mutation is the most common mutation, in which splicing change c.21522 +3A > G is hotspot mutation in Chinese NM patients.
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http://dx.doi.org/10.1007/s13760-020-01542-9DOI Listing
March 2021

An "over-fused middle cerebral artery" anomaly: a case report.

BMC Neurol 2021 Mar 17;21(1):123. Epub 2021 Mar 17.

Department of Radiology, Peking University Shougang Hospital, Jinyuanzhuang No.9, Shijingshan, Beijing, China.

Background: MCA has several anomalies, such as accessory MCA, duplicated MCA and twig-like MCA, up to now all these reported anomalies were hypothesized to due to the failure in fusion of the primitive arterial network. No anomaly of over fused MCA has been reported.

Case Presentation: A 59- year- old male was hospitalized with a history of paroxysmal slurred speech and left side headache for a week, his blood pressure was 160/80 mmHg and he manifested mild incomplete motor aphasia at the time of admission. The head and neck CTA and DSA all presented a huge and tortuous left MCA, we diagnosed it an anomaly and termed it over-fused MCA. The patient's speech impairment and headache were relieved by controlling his blood pressure.

Conclusions: Such an anomaly of over-fused MCA is reported for the first time, it's not needed to put special intervention on the anomaly of the patient temporarily, but more observation are needed.
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http://dx.doi.org/10.1186/s12883-021-02147-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972202PMC
March 2021

Data-driven method to infer the seizure propagation patterns in an epileptic brain from intracranial electroencephalography.

PLoS Comput Biol 2021 Feb 17;17(2):e1008689. Epub 2021 Feb 17.

Aix Marseille Univ, INSERM, INS, Inst Neurosci Syst, Marseille, France.

Surgical interventions in epileptic patients aimed at the removal of the epileptogenic zone have success rates at only 60-70%. This failure can be partly attributed to the insufficient spatial sampling by the implanted intracranial electrodes during the clinical evaluation, leading to an incomplete picture of spatio-temporal seizure organization in the regions that are not directly observed. Utilizing the partial observations of the seizure spreading through the brain network, complemented by the assumption that the epileptic seizures spread along the structural connections, we infer if and when are the unobserved regions recruited in the seizure. To this end we introduce a data-driven model of seizure recruitment and propagation across a weighted network, which we invert using the Bayesian inference framework. Using a leave-one-out cross-validation scheme on a cohort of 45 patients we demonstrate that the method can improve the predictions of the states of the unobserved regions compared to an empirical estimate that does not use the structural information, yet it is on the same level as the estimate that takes the structure into account. Furthermore, a comparison with the performed surgical resection and the surgery outcome indicates a link between the inferred excitable regions and the actual epileptogenic zone. The results emphasize the importance of the structural connectome in the large-scale spatio-temporal organization of epileptic seizures and introduce a novel way to integrate the patient-specific connectome and intracranial seizure recordings in a whole-brain computational model of seizure spread.
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http://dx.doi.org/10.1371/journal.pcbi.1008689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920393PMC
February 2021

Highly efficient U(VI) capture by amidoxime/carbon nitride composites: Evidence of EXAFS and modeling.

Chemosphere 2021 Jul 27;274:129743. Epub 2021 Jan 27.

School of Life Science, Shaoxing University, Huancheng West Road 508, Shaoxing, 312000, PR China. Electronic address:

The recovery of uranium from wastewater and safe treatment of U(VI)-containing wastewater are of great important to ensure the sustainable development of nuclear-related energy. Although abundant studies of U(VI) sorption on various adsorbents have been widely achieved, U(VI) sorption at extreme pH and trace concentration is challenging issues due to limited sorption activity of natural adsorbents. The development of novel materials with highly efficient and excellent selectivity for capturing U(VI) from nuclear-related wastewater and seawater is highly desirable. In this study, amidoxime/carbon nitride (AO/g-CN) was fabricated and captured U(VI) under a variety of water chemistry. We demonstrated that AO/g-CN exhibited the high adsorption capacities (312 mg/g at pH 6.8), fast removal equilibrium (>98% at 10 min) and superior selectivity for U(VI) compared with the other radionuclides (e.g., 19.76 mg/g of Cs(I)). In addition, AO/g-CN exhibited the high uranium extraction capacity from natural seawater (9.55 mg/g at saturation time of 5.5 days) compared to vanadium (1.85 mg/g). U(VI) adsorption behavior at different pH can be excellently fitted by the surface complexation modeling with three inner sphere surface complexes (i.e., SOUO(CO), SO(UO)(OH) and SOUO species). According to XPS (X-ray Photoelectron Spectroscopy) analysis, the strong complexation of U(VI) with AO groups retained in CN nanosheet. The split of U-O subshell and the occurrence of U-C shell further demonstrated inner-sphere surface complexation by EXAFS (X-Ray Absorption Fine Structure) spectra analyses. These results revealed that the high potential of AO/g-CN materials for selective U(VI) capture from wastewater and seawater.
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http://dx.doi.org/10.1016/j.chemosphere.2021.129743DOI Listing
July 2021

Dual stimuli-responsive polypeptide-calcium phosphate hybrid nanoparticles for co-delivery of multiple drugs in cancer therapy.

Colloids Surf B Biointerfaces 2021 Apr 24;200:111586. Epub 2021 Jan 24.

Shanxi Academy of Analytical Science, Taiyuan, 030006, China. Electronic address:

In this study, a new type of polypeptide, crosslinked methoxy poly(ethylene glycol)-g-poly(aspartic acid)-g-tyrosine (CPPT), was synthesized via a green and simple one-pot polymerization method. With the disulfide-crosslinked interlayer and the CaP shell, the pH and redox dual-sensitive polypeptide-based organic-inorganic hybrid nanoparticles encapsulated curcumin (Cur) into the hydrophobic core of micelles and loaded doxorubicin hydrochloride (DOX) on the hydrophilic segment of micelles as well as CaP shell. The spherical Cur- and DOX-loaded nanoparticles (CPPT@CaP-CD) showed a hydrodynamics size of about 157.9 ± 3.9 nm. The premature leakage of drugs from the nanoparticles at physiological pH was efficiently restrained because of the enhanced structure integrity, whereas at acidic and hypoxia microenvironment the release of both drugs was promoted due to the rapid dissolution of the CaP shell and the break of the disulfide crosslinked network, facilitating the stimuli-responsive controllable drugs release. In vitro anticancer activity evaluation revealed that the co-loaded nanoparticles presented higher cytotoxicity against A549 cells compared with that of the free combination of Cur + DOX. Confocal laser scanning microscopy observation indicated that more DOX and Cur were released into the nucleus triggered by the up-regulated intracellular glutathione (GSH) concentration and decreased pH, displaying enhanced cell uptake. The self-assembling polypeptide-based dual-sensitive drug co-delivery system could be a promising platform for efficient chemotherapy.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111586DOI Listing
April 2021

Poly(aspartic acid)-based pH-responsive targeting co-delivery nanoparticles.

J Biomater Appl 2021 Jan 28:885328220988071. Epub 2021 Jan 28.

Large Apparatus Analysis and Test Centre, Shanxi Academy of Analytical Science, Taiyuan, China.

Encapsulation of therapeutic molecules into nanocarrier is an extensively explored strategy to treat cancer more effectively. In this study, pH-responsive targeting dual-agent delivery nanoparticles were prepared, into which hydrophilic doxorubicin hydrochloride (DOX) and hydrophobic curcumin (CUR) were entrapped. Tyrosine (Tyr) was grafted onto poly(aspartic acid) (PASP) to produce PASP-Tyr, the following reaction between hyaluronic acid (HA) and ethylenediamine (EDA) modified PASP-Tyr formed the nanocarrier HA-EDA-PASP-Tyr (HEPT), and the loading capacity was up to 50.9 ± 4.3% for CUR and 26.0 ± 1.9% for DOX. The spherical HEPT with the mean particle size of 142.9 ± 11.4 nm expanded and deformed into petaloid pattern with an increased size of about 2 µm when triggered by the acidic microenvironment. anticancer activity evaluation revealed that the co-loaded (DOX+CUR)@HEPT nanoparticles presented higher cytotoxicity against HCT-116 cells compared with that of the free combination of (DOX+CUR). Confocal laser scanning microscopy observation indicated that HEPT carrier promoted cellular uptake of drugs by means of active targeting capacity of HA ligand. With high loading capacity and tailored carrier structure, the nanoparticles formulations may offer a new strategy for cancer treatment.
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http://dx.doi.org/10.1177/0885328220988071DOI Listing
January 2021

Elevated serum uric acid and risk of cardiovascular or all-cause mortality in maintenance hemodialysis patients: A meta-analysis.

Nutr Metab Cardiovasc Dis 2021 02 25;31(2):372-381. Epub 2020 Nov 25.

Department of Nephrology, the Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong, China. Electronic address:

Background And Aims: Studies have shown inconsistent results about the association between serum uric acid (SUA) levels and mortality in hemodialysis patients. We performed this meta-analysis to determine whether higher SUA values comprised a risk factor of cardiovascular or all-cause mortality in maintenance hemodialysis patients.

Methods And Results: Pubmed, Embase and the Cochrane library were searched up to August 31, 2020 for the longitudinal studies that investigated the association between the elevated SUA and cardiovascular or all-cause mortality risk in maintenance hemodialysis patients. Pooled adjusted hazard ratios (HR) and corresponding 95% confidence interval (CI) were calculated using a random-effects model. We included 10 studies with an overall sample of 264,571 patients with hemodialysis in this meta-analysis. Patients with the highest SUA were associated with a decreased risk of cardiovascular mortality (HR = 0.72, 95% CI 0.59-0.87) compared with patients with the lowest SUA after adjustment for potential confounders in a random effects model. Moreover, for each increase of 1 mg/dl of SUA, the overall risks of all-cause and cardiovascular mortality decreased by 6% and 9%, respectively (HR = 0.94, 95% CI 0.90-0.99; HR = 0.91, 95% CI 0.89-0.94).

Conclusion: Elevated SUA levels are strongly and independently associated with lower risk of cardiovascular mortality in maintenance hemodialysis patients. More designed studies, especially randomized controlled trials, should be conducted to determine whether high SUA levels is an independent risk factor of all-cause mortality in hemodialysis patients.
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http://dx.doi.org/10.1016/j.numecd.2020.11.017DOI Listing
February 2021

[Activation of NOD like receptor protein 3 signaling pathway in vascular endothelial cells induced by heat stress can be inhibited by ethyl pyruvate].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2020 Nov;32(11):1367-1371

Department of Emergency, Hunan Provincial People's Hospital, Changsha 410005, Hunan, China. Corresponding author: Han Xiaotong, Email:

Objective: To investigate whether the activation of NOD like receptor protein 3 (NLRP3) signaling pathway in vascular endothelial cells induced by heat stress (HS) could be inhibited by ethyl pyruvate (EP).

Methods: Human umbilical vein endothelial cells (HUVEC) were cultured in vitro, and the cells in logarithmic growth phase were taken to carry out experiment. Different temperatures gradients (39, 41, 43 centigrade for 4-hour HS) and different duration gradients (43 centigrade continuously HS respectively for 2, 3, 4 hours) were set up respectively. For HS group, HUVECs were placed in incubators with corresponding different conditions to carry out HS, then 43 centigrade persisting for 4-hour HS (43 centigrade, 4 hours) was selected as the final experimental condition; during HS, EP 10 mmol/L was added. For control group, the cells were synchronously cultured in 37 centigrade cell incubator. The protein expression of NLRP3 in HUVEC and activity of aspartate specific cysteine protease 1 (caspase-1) were detected with Western blotting; enzyme linked immunosorbent assay (ELISA) was used to detect the released levels of interleukins (IL-18 and IL-1β) in the cell culture supernatant fluid after HS.

Results: After HS, the protein expression level of NLRP3 in HUVEC was increased with the increasing of HS temperature or extension of exposure duration in HS condition, and reached to the highest in 43 centigrade for 4 hours. Compared with control group, there was significant difference [NLRP3 protein expression (NLRP3/GAPDH): 1.54±0.08 vs. 0.97±0.17, P < 0.05]; after EP intervention, the expression of NLRP3 and the activation of caspase-1 in HUVEC were significantly lower than those in HS group [NLRP3 protein expression (NLRP3/GAPDH): 1.15±0.07 vs. 1.57±0.09, caspase-1 activity: 40.87±6.54 vs. 59.75±9.92, both P < 0.05], moreover, the released levels of IL-18 and IL-1β in cell supernatant were also significantly decreasing than those in HS group [IL-18 (ng/L): 1.09±0.08 vs. 1.41±0.13, IL-1β (ng/L): 1.38±0.10 vs. 2.02±0.10, both P < 0.05].

Conclusions: The activation of NLRP3 signaling pathway in vascular endothelial cells induced by HS could be significantly inhibited by EP, which helps to reduce the release of inflammatory cytokines from vascular endothelial cells induced by HS.
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http://dx.doi.org/10.3760/cma.j.cn121430-20200715-00527DOI Listing
November 2020

Multifunctional role of a fungal pathogen-secreted laccase 2 in evasion of insect immune defense.

Environ Microbiol 2021 02 6;23(2):1256-1274. Epub 2021 Jan 6.

Biotechnology Research Center, State Cultivation Base of Crop Stress Biology for Southern Mountainous Land of Southwest University, Southwest University, Chongqing, 400715, P. R. China.

Laccases are widely present in bacteria, fungi, plants and invertebrates and involved in a variety of physiological functions. Here, we report that Beauveria bassiana, an economic important entomopathogenic fungus, secretes a laccase 2 (BbLac2) during infection that detoxifies insect immune response-generated reactive oxygen species (ROS) and interferes with host immune phenoloxidase (PO) activation. BbLac2 is expressed in fungal cells during proliferation in the insect haemocoel and can be found to distribute on the surface of haemolymph-derived in vivo fungal hyphal bodies or be secreted. Targeted gene-knockout of BbLac2 increased fungal sensitivity to oxidative stress, decreased virulence to insect, and increased host PO activity. Strains overexpressing BbLac2 showed increased virulence, with reduced host PO activity and lowered ROS levels in infected insects. In vitro assays revealed that BbLac2 could eliminate ROS and oxidize PO substrates (phenols), verifying the enzymatic functioning of the protein in detoxification of cytotoxic ROS and interference with the PO cascade. Moreover, BbLac2 acted as a cell surface protein that masked pathogen associated molecular patterns (PAMPs), enabling the pathogen to evade immune recognition. Our data suggest a multifunctional role for fungal pathogen-secreted laccase 2 in evasion of insect immune defenses.
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http://dx.doi.org/10.1111/1462-2920.15378DOI Listing
February 2021

Aluminum-based metal-organic frameworks (CAU-1) highly efficient UO and TcO ions immobilization from aqueous solution.

J Hazard Mater 2021 Apr 8;407:124729. Epub 2020 Dec 8.

School of Life Science, Shaoxing University, Huancheng West Road 508, Shaoxing 312000, PR China. Electronic address:

In this research, an Al-based metal-organic framework (MOFs), CAU-1 was prepared through complexation between 2-aminoterephthalic acid and Al (III) by solvothermal approach, and simple operation and cost-effective synthetic route. The objective was to immobilize the typical positive/negative radionuclide ions (UO/TcO) in aqueous solution. The synthesized CAU-1 was characterized by XRD, FT-IR, TGA, FESEM, TEM-SAED, pH, XPS and N physisorption analysis. The structure of CAU-1 possessed excellent thermostability, rich functional groups (‒NH and ‒OH groups), as well as large surface area (1636.3 m/g) and the micropore volume (0.51 m/g). Furthermore, batch experiments demonstrated that CAU-1 with superior adsorption capacity was 648.37 (UO) mg/g and 692.33 (ReO) mg/g calculating from Langmuir isotherm model, respectively. Thermodynamic investigation showed the adsorption process was endothermic and spontaneous. In addition, the adsorption mechanism of ReO ion onto CAU-1 could be electrostatic attraction and chelation effect, while for UO ion, was mainly chelation effect induced by nitrogen-containing and oxygen-containing functional groups. Hence, the inexpensive and high-capacity CAU-1 could be considered as a practical material for sequestrations of radioactive pollutants from water environment.
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http://dx.doi.org/10.1016/j.jhazmat.2020.124729DOI Listing
April 2021

Effects of whole body vibration exercise on lumbar-abdominal muscles activation for patients with chronic low back pain.

BMC Sports Sci Med Rehabil 2020 Dec 10;12(1):78. Epub 2020 Dec 10.

Department of Sport Rehabilitation, Shanghai University of Sport, 399 Changhai RD, Shanghai, China.

Background: Whole body vibration (WBV) training as an intervention method can cure chronic low back pain (CLBP). Different WBV parameters exert different effects on lumbar-abdominal muscle performance. Currently, there is a lack of study researched the influence of WBV training on patients with CLBP by lumbar-abdominal muscle activity. Therefore, this study aimed to investigate how WBV and exercise and their interactions influence lumbar-abdominal muscle activity in patients with CLBP.

Methods: a group of ambulatory patients with chronic low back pain. Muscle activities of the multifidus (MF), erector spinae (ES), abdominal oblique externus muscle (AOE) and the rectus abdominis muscle (RA) were measured by surface electromyography, whereas participants performed 4 different exercises (single bridge, plank, side stay and V crunch) during three whole body vibration conditions and a no-vibration condition in a single experimental session.

Results: Compared with the same exercises without whole body vibration, muscle activity increased when whole body vibration was added to the exercises. MF; the WBV frequency (P = 0.002,) and exercise (P < 0.001) presented significant effects on the root mean square of MF, whereas exercise * frequency (P = 0.044) also resulted in significant interaction effects. ES: the significant differences were detected at WBV frequency (P < 0.001), exercise (P < 0.001), the interaction effect of exercise and frequency (P = 0.225) was no significant. RA: the significant difference was detected at WBV frequency (P = 0.018), the effect of exercise (P = 0.590) and the exercise * frequency interaction (P = 0.572) were no significant. AOE: the significant difference was detected at WBV frequency (P < 0.001), the effect of exercise (P = 0.152) and the exercise * frequency interaction (P = 0.380) were no significant.

Conclusion: Adding whole body vibration to exercise could increase muscle activation of lumbar-abdominal muscle in patients with CLBP. The optimum frequency for lumbar-abdominal muscles is 15 Hz. The best exercises include plank for multifidus and erector spinae, V crunch for rectus abdominis and single bridge for abdominal oblique externus.

Clinical Registration: Trial registration: ChiCTR-TRC-13003708 . Registered 19 October 2013.

The Code Of Ethical Approval: 2014008.
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http://dx.doi.org/10.1186/s13102-020-00226-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731765PMC
December 2020

A nomogramic model based on clinical and laboratory parameters at admission for predicting the survival of COVID-19 patients.

BMC Infect Dis 2020 Nov 30;20(1):899. Epub 2020 Nov 30.

Department of Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, China.

Background: COVID-19 has become a major global threat. The present study aimed to develop a nomogram model to predict the survival of COVID-19 patients based on their clinical and laboratory data at admission.

Methods: COVID-19 patients who were admitted at Hankou Hospital and Huoshenshan Hospital in Wuhan, China from January 12, 2020 to March 20, 2020, whose outcome during the hospitalization was known, were retrospectively reviewed. The categorical variables were compared using Pearson's χ-test or Fisher's exact test, and continuous variables were analyzed using Student's t-test or Mann Whitney U-test, as appropriate. Then, variables with a P-value of ≤0.1 were included in the log-binomial model, and merely these independent risk factors were used to establish the nomogram model. The discrimination of the nomogram was evaluated using the area under the receiver operating characteristic curve (AUC), and internally verified using the Bootstrap method.

Results: A total of 262 patients (134 surviving and 128 non-surviving patients) were included in the analysis. Seven variables, which included age (relative risk [RR]: 0.905, 95% confidence interval [CI]: 0.868-0.944; P < 0.001), chronic heart disease (CHD, RR: 0.045, 95% CI: 0.0097-0.205; P < 0.001, the percentage of lymphocytes (Lym%, RR: 1.125, 95% CI: 1.041-1.216; P = 0.0029), platelets (RR: 1.008, 95% CI: 1.003-1.012; P = 0.001), C-reaction protein (RR: 0.982, 95% CI: 0.973-0.991; P < 0.001), lactate dehydrogenase (LDH, RR: 0.993, 95% CI: 0.990-0.997; P < 0.001) and D-dimer (RR: 0.734, 95% CI: 0.617-0.879; P < 0.001), were identified as the independent risk factors. The nomogram model based on these factors exhibited a good discrimination, with an AUC of 0.948 (95% CI: 0.923-0.973).

Conclusions: A nomogram based on age, CHD, Lym%, platelets, C-reaction protein, LDH and D-dimer was established to accurately predict the prognosis of COVID-19 patients. This can be used as an alerting tool for clinicians to take early intervention measures, when necessary.
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http://dx.doi.org/10.1186/s12879-020-05614-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7702207PMC
November 2020

Surface-layer protein produced by Lactobacillus crispatus JCM 2009 ameliorates lipopolysaccharide-induced inflammation through autophagy cross-talk with the NF-κB signaling pathway.

Int J Biol Macromol 2021 Jan 29;166:633-640. Epub 2020 Oct 29.

School of Food Science and Technology, Jiangnan University, 1800 Lihu Avenue, Wuxi, Jiangsu 214122, China. Electronic address:

In recent years, studies on immunomodulation by surface-layer proteins (Slps) have mainly focused on Lactobacillus acidophilus, there is little information on Slp from L. crispatus and its intestinal immunomodulatory mechanisms in macrophages. In our study, the anti-inflammatory actions of Slp derived from L. crispatus JCM 2009 and its related molecular mechanisms were investigated. We initially found that incubation with Slp (5-10 μg/mL) for 4 h significantly inhibited nitric oxide (NO) and prostaglandin E (PGE) production in LPS-stimulated RAW264.7 cells (P < 0.001). We then found that Slp inhibited the inflammatory response by regulating the PI3K/AKT/mTOR signaling pathway and activating autophagy in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Furthermore, ELISA and Western blotting results demonstrated that the NF-κB signaling pathway positively regulated autophagic activity to inhibit the productions of PGE and NO during this inflammatory response. And p65 was identified as a potentially important NF-κB signaling pathway molecule mediating the effects of Slp on the LPS-induced inflammatory response in RAW264.7 cells. Our findings provide the novel perspective that Slp exerts its anti-inflammatory effects through the activation of autophagy, making it a promising bioactive ingredient for the development of functional foods.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.10.221DOI Listing
January 2021

VEP atlas: An anatomic and functional human brain atlas dedicated to epilepsy patients.

J Neurosci Methods 2021 01 24;348:108983. Epub 2020 Oct 24.

Aix Marseille Univ, INSERM, INS, Inst Neurosci Syst, Marseille, France. Electronic address:

Background: Several automated parcellation atlases of the human brain have been developed over the past decades, based on various criteria, and have been applied in basic and clinical research.

New Method: Here we present the Virtual Epileptic Patient (VEP) atlas that offers a new automated brain region parcellation and labeling, which has been developed for the specific use in the domains of epileptology and functional neurosurgery and is able to apply at individual patient's level.

Results: It comprises 162 brain regions, including 73 cortical and 8 subcortical regions per hemisphere. We demonstrate the successful application of the VEP atlas in a cohort of 50 retrospective patients. The structural organization is complemented by the functional variation of stereotactic intracerebral EEG (SEEG) signal data features establishing brain region-specific 3d-maps.

Comparison With Existing Methods: The VEP atlas integrates both anatomical and functional definitions in the same atlas, adapted to applications for epilepsy patients and individualizable.

Conclusion: The covariation of structural and functional organization is the basis for current efforts of patient-specific large-scale brain network modeling exploiting virtual brain technologies for the identification of the epileptogenic regions in an ongoing prospective clinical trial EPINOV.
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http://dx.doi.org/10.1016/j.jneumeth.2020.108983DOI Listing
January 2021

Proteomic analysis of sex differences in hyperoxic lung injury in neonatal mice.

Int J Med Sci 2020 2;17(16):2440-2448. Epub 2020 Sep 2.

Department of Neonatology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University; the Pediatric Diagnosis and Treatment Respiratory Key Laboratory of Huai'an, Huai'an 223300, China.

Sex-specific differences in the severity of bronchopulmonary dysplasia (BPD) are due to different susceptibility to hyperoxic lung injury, but the mechanism is unclear. In this study, neonatal male and female mouse pups (C57BL/6J) were exposed to hyperoxia and lung tissues were excised on postnatal day 7 for histological analysis and tandem mass tags proteomic analysis. We found that the lung sections from the male mice following postnatal hyperoxia exposure had increased alveolar simplification, significant aberrant pulmonary vascularization and arrest in angiogenesis compared with females. Comparison of differentially expressed proteins revealed 377 proteins unique to female and 425 unique to male as well as 750 proteins in both male and female. Bioinformatics analysis suggested that several differentially expressed proteins could contribute to the differences in sex-specific susceptibility to hyperoxic lung injury. Our results may help identify sex-specific biomarkers and therapeutic targets of BPD.
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http://dx.doi.org/10.7150/ijms.42073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532490PMC
September 2020

Genomic amplification of long noncoding RNA HOTAIRM1 drives anaplastic thyroid cancer progression via repressing miR-144 biogenesis.

RNA Biol 2021 04 20;18(4):547-562. Epub 2020 Sep 20.

Department of General Surgery, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.

Genomic aberrations are frequently found in anaplastic thyroid cancer (ATC). However, the functional genes in aberrantly genomic regions are largely unclear. In this study, we identified a long noncoding RNA (lncRNA) HOTAIRM1, whose encoding gene was amplified and expression was upregulated in ATC compared with papillary thyroid cancer and normal thyroid. Increased genomic copy number and expression of were both correlated with poor survival of ATC patients. Functional assays revealed that HOTAIRM1 promoted proliferation, inhibited apoptosis, and promoted migration and invasion of ATC cells , and promoted ATC tumour growth and metastasis . HOTAIRM1 was found to bind ILF3, repress the binding between ILF3 and precursor miR-144 (pre-miR-144), block the effects of ILF3 on stabilizing pre-miR-144, and therefore downregulate pre-miR-144. Intriguingly, HOTAIRM1 was also found to directly bind primary miR-144 (pri-miR-144), repress the binding between pri-miR-144 and DROSHA, block the processing of pri-miR-144 by DROSHA, and therefore upregulate pri-miR-144 and downregulate pre-miR-144. Thus, HOTAIRM1 remarkably downregulated pre-miR-144 and further downregulated miR-144. Knockdown of ILF3 and DROSHA abolished the effects of HOTAIRM1 on pre-miR-144 and miR-144. The expression of miR-144 was downregulated and reversely correlated with HOTAIRM1 in ATC. Via repressing miR-144 biogenesis, HOTAIRM1 upregulated MET and activated AKT signalling. miR-144 overexpression reversed the oncogenic roles of HOTAIRM1 in ATC. Altogether, these findings identified a genomic copy number amplified and highly expressed lncRNA HOTAIRM1, which exerted oncogenic roles via repressing miR-144 biogenesis in ATC. Our data suggested HOTAIRM1 as a potential prognostic biomarker and therapeutic target for ATC.
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http://dx.doi.org/10.1080/15476286.2020.1819670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971326PMC
April 2021

Silk-Based Biomaterials for Cardiac Tissue Engineering.

Adv Healthc Mater 2020 Sep 16:e2000735. Epub 2020 Sep 16.

Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Cardiovascular diseases are one of the leading causes of death globally. Among various cardiovascular diseases, myocardial infarction is an important one. Compared with conventional treatments, cardiac tissue engineering provides an alternative to repair and regenerate the injured tissue. Among various types of materials used for tissue engineering applications, silk biomaterials have been increasingly utilized due to their biocompatibility, biological functions, and many favorable physical/chemical properties. Silk biomaterials are often used alone or in combination with other materials in the forms of patches or hydrogels, and serve as promising delivery systems for bioactive compounds in tissue engineering repair scenarios. This review focuses primarily on the promising characteristics of silk biomaterials and their recent advances in cardiac tissue engineering.
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http://dx.doi.org/10.1002/adhm.202000735DOI Listing
September 2020

Nanoparticle-enhanced chemo-immunotherapy to trigger robust antitumor immunity.

Sci Adv 2020 Aug 28;6(35):eabc3646. Epub 2020 Aug 28.

Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China.

Mounting evidence suggests that immunotherapies are a promising new class of anticancer therapies. However, the immunosuppressive tumor microenvironment (TME), poor immunogenicity, and off-target toxicity hinder the broader implementation of immunotherapies. Here, we describe a novel strategy combining chemotherapy and immunotherapy to modulate the TME by systemically and concurrently delivering the chemotherapeutic agent SN38 (7-ethyl-10-hydroxycamptothecin) and the STING agonist DMXAA (5,6-dimethylxanthenone-4-acetic acid) into tumors using triblock copolymer nanoparticles, named PS3D1@DMXAA, which enhances antigen cross-presentation and induces the conversion of the immunosuppressive TME to immunogenic TME through the newly found synergistic function between SN38 and STING activation. PS3D1@DMXAA thus shows potent therapeutic efficacy in three mice tumor models and elicits remarkable therapeutic benefit when combined with anti-PD-1 therapy. Our engineered nanosystem offers a rational design of an effective immunotherapy combination regimen to convert uninflamed "cold" tumors into "hot" tumors, addressing the major challenges immunotherapies faced.
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http://dx.doi.org/10.1126/sciadv.abc3646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455183PMC
August 2020

Preparation and characterization of catechol-grafted chitosan/gelatin/modified chitosan-AgNP blend films.

Carbohydr Polym 2020 Nov 16;247:116643. Epub 2020 Jun 16.

College of Materials Science and Engineering, Taiyuan University of Technology, Taiyuan 030024, PR China; Key Laboratory of Interface Science and Engineering in Advanced Materials, Taiyuan University of Technology, Ministry of Education, Taiyuan 030024, PR China. Electronic address:

Due to the increasing environmental pollution caused by plastic materials, the chitosan (CS)-based biodegradable films is gradually popular. However, poor water solubility of CS, poor mechanical and water barrier properties of CS film limit its application in food packaging. In this study, new bio-based films containing catechol-modified chitosan (CSCT), catechol-modified chitosan-silver nanoparticles (CSCT-Ag NPs) and gelatin (G) were prepared to overcome the drawbacks of pure CS films. Chitosan was modified by catechol to improve the water solubility. Ag NPs were prepared by in-situ reduction using modified chitosan, which yielded particles with an average size of approximately 8 nm. An antibacterial film composed of the modified chitosan as a matrix incorporated with Ag NPs and G was prepared by the solution casting method. The addition of Ag NPs and G improved the tensile strength and water vapor resistance. The prepared membrane exhibited unique antibacterial activities against S. aureus and E. coli. In conclusion, the fabricated bio-nanocomposite indicated considerable potential for food packaging.
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http://dx.doi.org/10.1016/j.carbpol.2020.116643DOI Listing
November 2020

Proteome and lysine acetylome analysis reveals insights into the molecular mechanism of seed germination in wheat.

Sci Rep 2020 08 10;10(1):13454. Epub 2020 Aug 10.

Shandong Provincial Key Laboratory of Dryland Farming Technology/College of Agronomy, Qingdao Agricultural University, Qingdao Shandong, 266109, China.

Seed germination is the first stage in wheat growth and development, directly affecting grain yield and quality. As an important post-translation modification, lysine acetylation participates in diverse biological functions. However, little is known regarding the quantitative acetylproteome characterization during wheat seed germination. In this study, we generated the first comparative proteomes and lysine acetylomes during wheat seed germination. In total, 5,639 proteins and 1,301 acetylated sites on 722 proteins were identified at 0, 12 and 24 h after imbibitions. Several particularly preferred amino acids were found near acetylation sites, including KS, KT, KK, KR, KH, KF, KN, K*E, FK and K*D, in the embryos during seed germination. Among them, KH, KF, FK and KK were conserved in wheat. Biosynthetic process, transcriptional regulation, ribosome and proteasome pathway related proteins were significantly enriched in both differentially expressed proteins and differentially acetylated proteins through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. We also revealed that histone acetylation was differentially involved in epigenetic regulation during seed germination. Meanwhile, abscisic acid and stress related proteins were found with acetylation changes. In addition, we focused on 8 enzymes involved in carbohydrate metabolism, and found they were differentially acetylated during seed germination. Finally, a putative metabolic pathway was proposed to dissect the roles of protein acetylation during wheat seed germination. These results not only demonstrate that lysine acetylation may play key roles in seed germination of wheat but also reveal insights into the molecular mechanism of seed germination in this crop.
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http://dx.doi.org/10.1038/s41598-020-70230-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418024PMC
August 2020

[Phenotypic and genetic characteristics of a child with 7p15 deletion syndrome].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2020 Aug;37(8):855-858

Department of Pediatrics, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.

Objective: To explore the genetic basis for a child with multiple malformation and growth retardation.

Methods: The child was subjected to low-coverage massively parallel copy number variation sequencing (CNV-seq) based on next generation sequencing (NGS) technique.

Results: G-banding karyotyping analysis has found no abnormality in the boy and his parents. CNV-seq analysis discovered that the child has carried a heterozygous 4.36 Mb deletion (24 020 000-28 380 000) at 7p15.3p15.1. The same deletion was not found in either parent. The deletion has encompassed 28 OMIM genes including HOXA13, CYCS, DFNA5, HOXA11 and HOXA2. Among these, HOXA13 has been associated with distal limb deformity, hypospadias and cryptorchidism. HOXA1, HOXA3 and HOXA4 are involved in the formation of cardiac primordia and primordial tube, and HOXA2 is involved in the development of auditory system. The clinical phenotype of the child was consistent with that of 7p15 deletion syndrome.

Conclusion: Haploinsufficiency of HOXA1, HOXA2, HOXA3, HOXA4 and HOXA13 genes may underlie the clinical phenotype of the child, which is comparable to 7p15 deletion syndrome.
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http://dx.doi.org/10.3760/cma.j.issn.1003-9406.2020.08.012DOI Listing
August 2020

Label-free fluorescent sensor for one-step lysozyme detection via positively charged gold nanorods.

Anal Bioanal Chem 2021 Mar 23;413(6):1541-1547. Epub 2020 Jul 23.

College of Tobacco Science, Henan Agricultural University, Zhengzhou, 450002, Henan, China.

In the article, a simple and label-free strategy was proposed for the sensitive detection of lysozyme based on the fluorescence quenching of positively charged gold nanorods ((+)AuNRs) to DNA-templated silver nanoclusters (DNA/AgNCs). To construct the sensor, a DNA template was designed with a C-rich sequence at the 5'-terminal for the synthesis of AgNCs, while a lysozyme binding aptamer (LBA) at the 3'-terminal for the recognition of lysozyme, and such DNA/AgNCs was used as the fluorescence probe. Meantime, the fluorescence signal of such DNA/AgNCs can be quenched based on the electrostatic adsorption of them with (+)AuNRs, due to the surface energy transfer. In the presence of lysozyme, the specific binding happened between the LBA section of DNA/AgNCs and lysozyme, inducing the reduction of the total charge of DNA/AgNCs and weakening the adsorption of them with (+)AuNRs, which directly resulting in the recovery of the fluorescence signal. Besides, the fluorescence signal recovery of DNA/AgNCs has a linear positive proportional relationship with lysozyme concentration in the range of 10 pM-2.0 nM under the optimal conditions. Moreover, a satisfactory recovery (99.6-107.2%) was obtained while detecting lysozyme in human serum samples. Graphical abstract A simple and label-free strategy was proposed for the sensitive detection of lysozyme based on the fluorescence quenching of positively charged gold nanorods ((+)AuNRs) to DNA-templated silver nanoclusters (DNA/AgNCs).
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http://dx.doi.org/10.1007/s00216-020-02814-2DOI Listing
March 2021

Preparation, characterization and antibacterial activity of a novel soluble polymer derived from xanthone and O-carboxymethyl-N, N, N-trimethyl chitosan.

Int J Biol Macromol 2020 Dec 18;164:836-844. Epub 2020 Jul 18.

Key Laboratory of Interface Science and Engineering in Advanced Materials, Ministry of Education, Taiyuan University of Technology, Taiyuan 030024, PR China; College of Materials Science and Engineering, Taiyuan University of Technology, Taiyuan 030024, PR China.

In this contribution, a novel soluble and antibacterial polymer, O-xanthonyl-chitosan (CTMC-Xan), was synthesized successfully by grafting 1,3-dihydroxy-xanthone (Xan) to the side chains of O-carboxymethyl-N, N, N-trimethyl chitosan (CTMC). The chemical structure and physical properties of the polymer were analyzed by H NMR, FT-IR spectra, UV spectra and XRD. The results showed that Xan could covalently bond with the carboxyl groups of CTMC by esterification at a grafting ratio of 9.1%. XRD patterns indicated that CTMC-Xan does not exhibit crystallization. The solubility tests showed that CTMC-Xan was completely dissolved and stable in neutral solution but unstable in acid or basic conditions. Moreover, it was found that the antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) of CTMC-Xan was much stronger than that of Xan and CTMC, and the minimal bactericidal concentration (MBC) was 125 μg·mL. Due to the enhanced solubility and antibacterial activity, CTMC-Xan could potentially serve as a desirable biomaterial for food and pharmaceutical applications.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.07.147DOI Listing
December 2020

Coinhibition of activated p38 MAPKα and mTORC1 potentiates stemness maintenance of HSCs from SR1-expanded human cord blood CD34 cells via inhibition of senescence.

Stem Cells Transl Med 2020 12 29;9(12):1604-1616. Epub 2020 Jun 29.

Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

The stemness of ex vivo expanded hematopoietic stem cells (HSCs) is usually compromised by current methods. To explore the failure mechanism of stemness maintenance of human HSCs, which were expanded from human umbilical cord blood (hUCB) CD34 cells, by differentiation inhibitor Stem Regenin 1 (SR1), an antagonist of aryl hydrocarbon receptor, we investigated the activity of p38 mitogen-activated protein kinase α (p38 MAPKα, p38α) and mammalian target of rapamycin complex 1 (mTORC1), and their effect on SR1-expanded hUCB CD34 cells. Our results showed that cellular senescence occurred in the SR1-expanded hUCB CD34 cells in which p38α and mTORC1 were successively activated. Furthermore, their coinhibition resulted in a further decrease in hUCB CD34 cell senescence without an effect on apoptosis, promoted the maintenance of expanded phenotypic HSCs without differentiation inhibition, increased the hematopoietic reconstitution ability of multiple lineages, and potentiated the long-term self-renewal capability of HSCs from SR1-expanded hUCB CD34 cells in NOD/Shi-scid/IL-2Rγ mice. Our mechanistic study revealed that senescence inhibition by our strategy was mainly attributed to downregulation of the splicesome, proteasome formation, and pyrimidine metabolism signaling pathways. These results suggest that coinhibition of activated p38α and mTORC1 potentiates stemness maintenance of HSCs from SR1-expanded hUCB CD34 cells via senescence inhibition. Thus, we established a new strategy to maintain the stemness of ex vivo differentiation inhibitor-expanded human HSCs via coinhibition of multiple independent senescence initiating signal pathways. This senescence inhibition-induced stemness maintenance of ex vivo expanded HSCs could also have an important role in other HSC expansion systems.
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http://dx.doi.org/10.1002/sctm.20-0129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695631PMC
December 2020