Publications by authors named "Ping Zhu"

1,226 Publications

  • Page 1 of 1

Style transfer in conditional GANs for cross-modality synthesis of brain magnetic resonance images.

Comput Biol Med 2022 Aug 2;148:105928. Epub 2022 Aug 2.

School of Design, Shanghai Jiao Tong University, Shanghai 200240, China.

Magnetic resonance imaging (MRI) has become one of the most standardized and widely used neuroimaging protocols in the detection and diagnosis of neurodegenerative diseases. In clinical scenarios, multi-modality MR images can provide more comprehensive information than single modality images. However, high-quality multi-modality MR images can be difficult to obtain in the actual diagnostic process due to various uncertainties. Efficient methods of modality complement and synthesis have aroused increasing attention in the research community. In this article, style transfer is introduced into conditional generative adversarial networks (cGAN) architecture. A cGAN model with hierarchical feature mapping and fusion (ST-cGAN) is proposed to address the cross-modality synthesis of MR images. In order to surmount the sole focus on the pixel-wise similarity as most cGAN-based methods do, the proposed ST-cGAN takes advantage of the style information and applies it to the synthetic image's content structure. Taking images of two modalities as conditional input, ST-cGAN extracts different levels of style features and integrates them with the content features to form the style-enhanced synthetic image. Furthermore, the proposed model is made robust to random noise by adding noise input to the generator. A comprehensive analysis is performed by comparing the proposed ST-cGAN with other state-of-the-art baselines based on four representative evaluation metrics. The experimental results on the IXI (Information eXtraction from Images) dataset verify the validity of the ST-cGAN from different evaluation perspectives.
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http://dx.doi.org/10.1016/j.compbiomed.2022.105928DOI Listing
August 2022

Development of clustered regularly interspaced short palindromic repeats/CRISPR-associated technology for potential clinical applications.

World J Clin Cases 2022 Jun;10(18):5934-5945

Department of Laboratory Medicine, Peking University Shenzhen Hospital, Shenzhen 518035, Guangdong Province, China.

The clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) proteins constitute the innate adaptive immune system in several bacteria and archaea. This immune system helps them in resisting the invasion of phages and foreign DNA by providing sequence-specific acquired immunity. Owing to the numerous advantages such as ease of use, low cost, high efficiency, good accuracy, and a diverse range of applications, the CRISPR-Cas system has become the most widely used genome editing technology. Hence, the advent of the CRISPR/Cas technology highlights a tremendous potential in clinical diagnosis and could become a powerful asset for modern medicine. This study reviews the recently reported application platforms for screening, diagnosis, and treatment of different diseases based on CRISPR/Cas systems. The limitations, current challenges, and future prospectus are summarized; this article would be a valuable reference for future genome-editing practices.
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http://dx.doi.org/10.12998/wjcc.v10.i18.5934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9254185PMC
June 2022

Short Sleep Duration as a Risk Factor for Depression, Anxiety and Fatigue in Patients with Leukemia.

Neuropsychiatr Dis Treat 2022 29;18:1573-1582. Epub 2022 Jul 29.

Department of Hematology, Chenzhou First People's Hospital, Chenzhou City, Hunan Province, People's Republic of China.

Objective: Our study aimed to investigate the level of depression, anxiety, and fatigue in patients with leukemias, and analyze the influence of sleep duration on the mental symptoms of patients with leukemias.

Methods: A total of 127 patients were enrolled in our study and completed the questionnaire survey. Self-Assessment Depression Scale (SDS), Self-Assessment Anxiety Scale (SAS), and the Fatigue Scale-14 (FS-14) were adopted. The patient's lifestyle information, including exercise, alcohol abuse, and smoking, was obtained from the patient's self-report.

Results: Depression score of patients with sleep duration >8 hours (long duration group) was 56.21±11.63, which was significantly lower than that of patients sleep duration between 6 and 8 hours (medium duration group) with 59.61±8.77 and patients sleep <6 hours (short duration group) with 64.82±6.42 (P = 0.007). Similarly, the anxiety score of long duration group, medium duration group and short duration group was 45.36±11.41, 48.26±6.96 and 53.53±5.87, respectively (P = 0.005). The fatigue score of short duration group is 8.47±2.45, which is higher than others (P = 0.046). To further identify the relationship, we evaluated physical fatigue and mental fatigue levels in patients with or without symptoms of depression. We found that patients with symptoms of depression have a higher score both in physical fatigue and mental fatigue (all p < 0.001). Similar trend was observed in patients with or without symptoms of anxiety (all p < 0.001). However, alzhough patients with leukemia in long duration group have the highest score of physical fatigue (p = 0.016), no significant difference in mental fatigue was found in different sleeping duration group (p = 0.587). Furthermore, multivariate analyses were conducted and revealed that sleep duration was the independent factor associated with depression (OR = 0.270, P = 0.003) and anxiety (OR = 0.473, P = 0.010).

Conclusion: For leukemia patients with short sleep duration, a prompt evaluation of their level of depression, anxiety, and fatigue and the initiation of timely interventions is essential.
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http://dx.doi.org/10.2147/NDT.S362229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9346604PMC
July 2022

Optimising fluid requirements after initial resuscitation: A pilot study evaluating mini-fluid challenge and passive leg raising test in patients with predicted severe acute pancreatitis.

Pancreatology 2022 Jul 8. Epub 2022 Jul 8.

Surgical and Translational Research Centre, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand; Applied Surgery and Metabolism Laboratory, School of Biological Sciences, University of Auckland, Auckland, New Zealand.

Background: The goals and approaches to fluid therapy vary through different stages of resuscitation. This pilot study was designed to test the safety and feasibility of a fluid therapy protocol for the second or optimisation stage of resuscitation in patients with predicted severe acute pancreatitis (SAP).

Methods: Spontaneously breathing patients with predicted SAP were admitted after initial resuscitation and studied over a 24-h period in a tertiary hospital ward. Objective clinical assessment (OCA; heart rate, mean arterial pressure, urine output, and haematocrit) was done at 0, 4, 8, 12, 18-20, and 24 h. All patients had mini-fluid challenge (MFC; 250 ml intravenous normal saline within 10 min) at 0 h and repeated at 4 and 8 h if OCA score ≥2. Patients who were fluid responsive (>10% change in stroke volume after MFC) received 5-10 ml/kg/h, otherwise 1-3 ml/kg/h until the next time point. Passive leg raising test (PLRT) was done at each time point and compared with OCA for assessing volume status and predicting fluid responsiveness.

Results: This fluid therapy protocol based on OCA, MFC, and PLRT and designed for the second stage of resuscitation was safe and feasible in spontaneously breathing predicted SAP patients. The PLRT was superior to OCA (at 0 and 8 h) for predicting fluid responsiveness and guiding fluid therapy.

Conclusions: This pilot study found that a protocol for intravenous fluid therapy specifically for the second stage of resuscitation in patients with predicted SAP was safe, feasible, and warrants further investigation.
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http://dx.doi.org/10.1016/j.pan.2022.07.001DOI Listing
July 2022

Effects of Sodium-Glucose Cotransporter-2 Inhibitors on Urine Albumin to Creatinine Ratio in Type 2 Diabetes Mellitus Patients and Medication Care.

J Diabetes Res 2022 20;2022:5854200. Epub 2022 Jul 20.

School of Nursing, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.

Objectives: The purpose of this study was to explore the effects of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on urine albumin to creatinine ratio (UACR) in type 2 diabetes mellitus (T2DM) patients and to recommend appropriate medication care scheme.

Methods: 8371 T2DM patients from four dapagliflozin studies and two canagliflozin studies were collected for analyzing with nonlinear mixed effect model (NONMEM). The change rates of UACR from baseline were intended to be evaluation indicators.

Results: In the present study, there was no significant difference in the effects on UACR using dapagliflozin or canagliflozin treatment in T2DM patients. The maximal effect ( ) and the treatment duration of reaching half of (ET) from SGLT-2 inhibitors on UACR in T2DM patients were -19.2% and 0.448 weeks, respectively. Further, the treatment duration to reach 25%, 50%, 75%, and 80% was 0.150 weeks, 0.448 weeks, 1.344 weeks, and 1.792 weeks, respectively. Namely, for achieving the plateau period (80% of ) of SGLT-2 inhibitors on UACR in T2DM patients, 10 mg/day dapagliflozin (or 100 mg/day canagliflozin) should be taken for at least 1.792 weeks.

Conclusions: To our knowledge, the present study explored the effects of SGLT-2 inhibitors on UACR in T2DM patients, meanwhile, recommended appropriate medication care scheme for the first time.
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http://dx.doi.org/10.1155/2022/5854200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9328955PMC
August 2022

Rates of operative intervention for infection after synthetic or autologous cranioplasty: a National Readmissions Database analysis.

J Neurosurg 2022 Jun 10:1-8. Epub 2022 Jun 10.

1Department of Neurological Surgery, University of Minnesota.

Objective: The aim of this study was to characterize the clinical utilization and associated charges of autologous bone flap (ABF) versus synthetic flap (SF) cranioplasty and to characterize the postoperative infection risk of SF versus ABF using the National Readmissions Database (NRD).

Methods: The authors used the publicly available NRD to identify index hospitalizations from October 2015 to December 2018 involving elective ABF or SF cranioplasty after traumatic brain injury (TBI) or stroke. Subsequent readmissions were further characterized if patients underwent neurosurgical intervention for treatment of infection or suspected infection. Survey Cox proportional hazards models were used to assess risk of readmission.

Results: An estimated 2295 SF and 2072 ABF cranioplasties were performed from October 2015 to December 2018 in the United States. While the total number of cranioplasty operations decreased during the study period, the proportion of cranioplasties utilizing SF increased (p < 0.001), particularly in male patients (p = 0.011) and those with TBI (vs stroke, p = 0.012). The median total hospital charge for SF cranioplasty was $31,200 more costly than ABF cranioplasty (p < 0.001). Of all first-time readmissions, 20% involved surgical treatment for infectious reasons. Overall, 122 SF patients (5.3%) underwent surgical treatment of infection compared with 70 ABF patients (3.4%) on readmission. After accounting for confounders using a multivariable Cox model, female patients (vs male, p = 0.003), those discharged nonroutinely (vs discharge to home or self-care, p < 0.001), and patients who underwent SF cranioplasty (vs ABF, p = 0.011) were more likely to be readmitted for reoperation. Patients undergoing cranioplasty during more recent years (e.g., 2018 vs 2015) were less likely to be readmitted for reoperation because of infection (p = 0.024).

Conclusions: SFs are increasingly replacing ABFs as the material of choice for cranioplasty, despite their association with increased hospital charges. Female sex, nonroutine discharge, and SF cranioplasty are associated with increased risk for reoperation after cranioplasty.
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http://dx.doi.org/10.3171/2022.4.JNS22301DOI Listing
June 2022

[Effects of in situ cross-linked graphene oxide-containing gelatin methacrylate anhydride hydrogel on wound vascularization of full-thickness skin defect in mice].

Zhonghua Shao Shang Za Zhi 2022 Jul;38(7):616-628

Guangdong Cardiovascular Institute, Department of Cardiac Surgery of Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.

To prepare graphene oxide (GO)-containing gelatin methacrylate anhydride (GelMA) hydrogel and to investigate the effects of in situ photopolymerized GO-GelMA composite hydrogel in wound vascularization of full-thickness skin defect in mice. The experimental study method was used. The 50 μL of 0.2 mg/mL GO solution was evenly applied onto the conductive gel, and the structure and size of GO were observed under field emission scanning electron microscope after drying. Human skin fibroblasts (HSFs) were divided into 0 μg/mL GO (without GO solution, the same as below) group, 0.1 μg/mL GO group, 1.0 μg/mL GO group, 5.0 μg/mL GO group, and 10.0 μg/mL GO group treated with GO of the corresponding final mass concentration, and the absorbance value was detected using a microplate analyzer after 48 h of culture to reflect the proliferation activity of cells (=6). HSFs and human umbilical vein vascular endothelial cells (HUVECs) were divided into 0 μg/mL GO group, 0.1 μg/mL GO group, 1.0 μg/mL GO group, and 5.0 μg/mL GO group treated with GO of the corresponding final mass concentration, and the migration rates of HSFs at 24 and 36 h after scratching (=5) and HUVECs at 12 h after scratching (=3) were detected by scratch test, and the level of vascular endothelial growth factor (VEGF) secreted by HSFs after 4, 6, and 8 h of culture was detected by enzyme-linked immunosorbent assay method (=3). The prepared GO-GelMA composite hydrogels containing GO of the corresponding final mass concentration were set as 0 μg/mL GO composite hydrogel group, 0.1 μg/mL GO composite hydrogel group, 1.0 μg/mL GO composite hydrogel group, and 5.0 μg/mL GO composite hydrogel group to observe their properties before and after cross-linking, and to detect the release of GO after soaking with phosphate buffer solution for 3 and 7 d (=3). The full-thickness skin defect wounds were made on the back of 16 6-week-old female C57BL/6 mice. The mice treated with in situ cross-linked GO-GelMA composite hydrogel containing GO of the corresponding final mass concentration were divided into 0 μg/mL GO composite hydrogel group, 0.1 μg/mL GO composite hydrogel group, 1.0 μg/mL GO composite hydrogel group, and 5.0 μg/mL GO composite hydrogel group according to the random number table, with 4 mice in each group. The general condition of wound was observed and the wound healing rate was calculated on 3, 7, and 14 d of treatment, the wound blood perfusion was detected by laser Doppler flowmetry on 3, 7, and 14 d of treatment and the mean perfusion unit (MPU) ratio was calculated, and the wound vascularization on 7 d of treatment was observed after hematoxylin-eosin staining and the vascular density was calculated (=3). The wound tissue of mice in 0 μg/mL GO composite hydrogel group and 0.1 μg/mL GO composite hydrogel group on 7 d of treatment was collected to observe the relationship between the distribution of GO and neovascularization by hematoxylin-eosin staining (=3) and the expression of VEGF by immunohistochemical staining. Data were statistically analyzed with analysis of variance for repeated measurement, one-way analysis of variance, and Tukey's method. GO had a multilayered lamellar structure with the width of about 20 μm and the length of about 50 μm. The absorbance value of HSFs in 10.0 μg/mL GO group was significantly lower than that in 0 μg/mL GO group after 48 h of culture (=7.64, <0.01). At 24 h after scratching, the migration rates of HSFs were similar in the four groups (>0.05); at 36 h after scratching, the migration rate of HSFs in 0.1 μg/mL GO group was significantly higher than that in 0 μg/mL GO group, 1.0 μg/mL GO group, and 5.0 μg/mL GO group (with values of 7.48, 10.81, and 10.20, respectively, <0.01). At 12 h after scratching, the migration rate of HUVECs in 0.1 μg/mL GO group was significantly higher than that in 0 μg/mL GO group, 1.0 μg/mL GO group, and 5.0 μg/mL GO group (with values of 7.11, 8.99, and 14.92, respectively, <0.01), and the migration rate of HUVECs in 5.0 μg/mL GO group was significantly lower than that in 0 μg/mL GO group and 1.0 μg/mL GO group (with values of 7.81 and 5.33, respectively, <0.05 or <0.01 ). At 4 and 6 h of culture, the VEGF expressions of HSFs in the four groups were similar (>0.05); at 8 h of culture, the VEGF expression of HSFs in 0.1 μg/mL GO group was significantly higher than that in 0 μg/mL GO group and 5.0 μg/mL GO group (with values of 4.75 and 4.48, respectively, <0.05). The GO-GelMA composite hydrogels in the four groups were all red liquid before cross-linking, which turned to light yellow gel after cross-linking, with no significant difference in fluidity. The GO in the GO-GelMA composite hydrogel of 0 μg/mL GO composite hydrogel group had no release of GO at all time points; the GO in the GO-GelMA composite hydrogels of the other 3 groups was partially released on 3 d of soaking, and all the GO was released on 7 d of soaking. From 3 to 14 d of treatment, the wounds of mice in the 4 groups were covered with hydrogel dressings, kept moist, and gradually healed. On 3, 7, and 14 d of treatment, the wound healing rates of mice in the four groups were similar (>0.05). On 3 d of treatment, the MPU ratio of wound of mice in 0.1 μg/mL GO composite hydrogel group was significantly higher than that in 0 μg/mL GO composite hydrogel group, 1.0 μg/mL GO composite hydrogel group, and 5.0 μg/mL GO composite hydrogel group (with values of 10.70, 11.83, and 10.65, respectively, <0.05 or <0.01). On 7 and 14 d of treatment, the MPU ratios of wound of mice in the four groups were similar (>0.05). The MPU ratio of wound of mice in 0.1 μg/mL GO composite hydrogel group on 7 d of treatment was significantly lower than that on 3 d of treatment (=14.38, <0.05), and that on 14 d of treatment was significantly lower than that on 7 d of treatment (=27.78, <0.01). On 7 d of treatment, the neovascular density of wound of mice on 7 d of treatment was 120.7±4.1 per 200 times of visual field, which was significantly higher than 61.7±1.3, 77.7±10.2, and 99.0±7.9 per 200 times of visual field in 0 μg/mL GO composite hydrogel group, 1.0 μg/mL GO composite hydrogel group, and 5.0 μg/mL GO composite hydrogel group (with values of 12.88, 7.79, and 6.70, respectively, <0.01), and the neovascular density of wound of mice in 1.0 μg/mL GO composite hydrogel group and 5.0 μg/mL GO composite hydrogel group was significantly higher than that in 0 μg/mL GO composite hydrogel group (with values of 5.10 and 6.19, respectively, <0.05). On 7 d of treatment, cluster of new blood vessels in wound of mice in 0.1 μg/mL GO composite hydrogel group was significantly more than that in 0 μg/mL GO composite hydrogel group, and the new blood vessels were clustered near the GO; a large amount of VEGF was expressed in wound of mice in 0.1 μg/mL GO composite hydrogel group in the distribution area of GO and new blood vessels. GO with mass concentration lower than 10.0 μg/mL had no adverse effect on proliferation activity of HSFs, and GO of 0.1 μg/mL can promote the migration of HSFs and HUVECs, and can promote the secretion of VEGF in HSFs. In situ photopolymerized of GO-GelMA composite hydrogel dressing can promote the wound neovascularization of full-thickness skin defect in mice and increase wound blood perfusion in the early stage, with GO showing an enrichment effect on angiogenesis, and the mechanism may be related to the role of GO in promoting the secretion of VEGF by wound cells.
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http://dx.doi.org/10.3760/cma.j.cn501225-20220314-00063DOI Listing
July 2022

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

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

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

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

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

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

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

High-throughput screening of stable and efficient double inorganic halide perovskite materials by DFT.

Sci Rep 2022 Jul 25;12(1):12633. Epub 2022 Jul 25.

College of Electronic and Electrical Engineering, Shangqiu Normal University, Shangqiu, 476000, China.

Perovskite solar cells have become the most promising third-generation solar cells because of their superior physical-chemical properties and high photoelectric conversion efficiency. However, the current obstacles to commercialization of perovskite solar cells are their poor stability and harmful elements. How to find high-efficiency, high-stability and non-toxic perovskite materials from thousands of possible perovskite crystals is the key to solve this problem. In this paper, the inorganic halide double perovskite ABX and its crystal structure are considered, and the data mining algorithm in informatics is introduced into the high-throughput computing data to analyze various elements in nature to study the perovskite materials that can meet the requirements of high performance. The photoelectric conversion properties and stability of 42 inorganic double perovskite materials are studied based on density functional theory (DFT). The results show that the tolerance factors of 39 crystals are between 0.8 and 1.10, indicating that these crystals have stable perovskite structure. In addition, the dielectric function, PDOS, elastic modulus, shear modulus and poison's ratio of these crystals are analyzed. According to the above theoretical simulation results, three candidate materials for ideal light absorption are presented. This can provide a theoretical basis for the industrial application of perovskite solar cells.
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http://dx.doi.org/10.1038/s41598-022-16221-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314419PMC
July 2022

Readmission risk of malignant brain tumor patients undergoing laser interstitial thermal therapy (LITT) and stereotactic needle biopsy (SNB): a covariate balancing weights analysis of the National Readmissions Database (NRD).

J Neurooncol 2022 Jul 23. Epub 2022 Jul 23.

Department of Neurological Surgery, University of Minnesota, 420 Delaware St SE MMC 96 Room D-429, Minneapolis, Minnesota, 55455, USA.

Purpose: Despite procedural similarities between laser interstitial thermal therapy (LITT) and stereotactic needle biopsy (SNB), LITT induces delayed, pro-inflammatory responses not associated with SNB that may increase the risk of readmission within 30- or 90- days. Here, we explore this hypothesis.

Methods: We queried the National Readmissions Database (NRD, 2010-18) for malignant brain tumor patients who underwent elective LITT or SNB using International Classification of Diseases codes. Readmissions were defined as non-elective inpatient hospitalizations. Survey regression methods and a weighted analysis were utilized to adjust for demographic and clinical differences between LITT and SNB cohorts.

Results: During the study period, an estimated 685 malignant brain patients underwent elective LITT and 15,177 underwent elective SNB. Patients undergoing LITT and SNB exhibited comparable median lengths of hospital stay [IQR; LITT = 2 (1, 3); SNB = 1 (1, 2); p = 0.820]. Likelihood of routine discharge was not significantly different between the two procedures (p = 0.263). No significant differences were observed in the odds of 30- or 90-day unplanned readmission between the LITT and SNB cohorts after multivariable adjustment (all p ≥ 0.177). The covariate balancing weighted analysis confirmed comparable 30 or 90-day readmission risk between LITT and SNB treated patients (all p ≥ 0.201).

Conclusion: The likelihood of 30- and 90-day readmission for malignant brain tumor patients who underwent LITT or SNB are comparable, supporting the safety profile of LITT as therapy for malignant brain cancers.
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http://dx.doi.org/10.1007/s11060-022-04093-6DOI Listing
July 2022

Metabolic engineering of yeasts for green and sustainable production of bioactive ginsenosides F2 and 3,20-Di--Glc-DM.

Acta Pharm Sin B 2022 Jul 27;12(7):3167-3176. Epub 2022 Apr 27.

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, NHC Key Laboratory of Biosynthesis of Natural Products, CAMS Key Laboratory of Enzyme and Biocatalysis of Natural Drugs, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.

Both natural ginsenoside F2 and unnatural ginsenoside 3,20-Di--Glc-DM were reported to exhibit anti-tumor activity. Traditional approaches for producing them rely on direct extraction from , enzymatic catalysis or chemical synthesis, all of which result in low yield and high cost. Metabolic engineering of microbes has been recognized as a green and sustainable biotechnology to produce natural and unnatural products. Hence we engineered the complete biosynthetic pathways of F2 and 3,20-Di--Glc-DM in the CRISPR/Cas9 system. The titers of F2 and 3,20-Di--Glc-DM were increased from 1.2 to 21.0 mg/L and from 82.0 to 346.1 mg/L at shake flask level, respectively, by multistep metabolic engineering strategies. Additionally, pharmacological evaluation showed that both F2 and 3,20-Di--Glc-DM exhibited anti-pancreatic cancer activity and the activity of 3,20-Di--Glc-DM was even better. Furthermore, the titer of 3,20-Di--Glc-DM reached 2.6 g/L by fed-batch fermentation in a 3 L bioreactor. To our knowledge, this is the first report on demonstrating the anti-pancreatic cancer activity of F2 and 3,20-Di--Glc-DM, and achieving their biosynthesis by the engineered yeasts. Our work presents an alternative approach to produce F2 and 3,20-Di--Glc-DM from renewable biomass, which lays a foundation for drug research and development.
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http://dx.doi.org/10.1016/j.apsb.2022.04.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9293705PMC
July 2022

Recombinant jurkat cells (HMGN2-T cells) secrete cytokines and inhibit the growth of tumor cells.

J Mol Histol 2022 Jul 21. Epub 2022 Jul 21.

Department of Hematology, Peking University First Hospital, No.8 Xishiku Street, Xicheng District, 100034, Beijing, China.

High Mobility Group Chromosomal Protein N2 (HMGN2) can recognize tumor cells and enhance the anti-tumor effect of immune cells. This study aimed to establish a lentiviral vector of recombinant HMGN2 gene, establish recombinant T cells (HMGN2-T cells), and observe their anti-tumor effects. Total RNA was isolated from peripheral blood mononuclear cells. HMGN2, cluster of differentiation (CD) 8 A, CD28, CD137, and CD3ζ genes were amplified and connected. Jurkat cells were transfected with the recombinant lentivirus vector. The viability, apoptosis, and cell cycle of HMGN2-T cells were detected using Cell Counting Kit-8 assay and flow cytometry. The co-culture was performed by adding HMGN2-T cells to tumor cells with different effect-to-target (E:T) ratios. The cytotoxic activity was measured by lactate dehydrogenase (LDH) releasing assay. The sequences of HMGN2, CD8A, CD28, CD137, and CD3ζ gene plasmids were confirmed using gene sequencing. After the lentiviral transfection for 72 h, green fluorescence cells (HMGN2-T cells) could be seen. Cell viability and apoptosis were increased in HMGN2-T cells. The cytokine levels of interleukin 2 (IL-2) and tumor necrosis factor α (TNF-α) increased in cell supernatants of HMGN2-T cells. The percentage of G0/G1 phase cells was lower, the rate of S phase cells was higher in HMGN2-T cells than control cells. The co-culture of HMGN2-T cells and tumor cells could promote the cytokines' release. The LDH level was increased with the elevation of E:T ratios. In conclusion, the HMGN2-T cells were well-established and have the effect of secreting cytokines and killing tumor cells.
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http://dx.doi.org/10.1007/s10735-022-10084-8DOI Listing
July 2022

One-pot synthesis of α-Linolenic acid nanoemulsion-templated drug-loaded silica mesocomposites as efficient bactericide against drug-resistant Mycobacterium tuberculosis.

Eur J Pharm Sci 2022 Sep 15;176:106261. Epub 2022 Jul 15.

Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Jiangsu Province Engineering Research Center of Antibody Drug, Key Laboratory of Antibody Technique of National Health Commission, Nanjing Medical University, Nanjing 211166, China; The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Xinjiang Production & Construction Corps Key Laboratory of Protection and Utilization of Biological Resources in Tarim Basin, Tarim University, Alar 843300, China. Electronic address:

Nowadays, pathogenic infection has posed a severe threat to the public health and environmental sanitation, urging a continuous search of efficacious and safe bactericidal agents of various formulated forms. Here, a facile one-pot hydrothermal preparation of mesoporous silica nanoparticles using ultrasonication-assisted nanoemulsion of α-Linolenic acid (α-LA) as template was developed. The formed silica mesocomposite at water/fatty-acid surface provides an easy yet green synthesis route, which can be generalized for the further encapsulation of hydrophobic drugs such as antimycobacterial Rifampicin (RIF). The obtained α-LA nanoemulsion-templated silica nanoparticles (LNS NPs), with a weight content of ∼17% α-LA in the composite, showed apparent antibacterial effect against Staphylococcus aureus (S. aureus). By comparison, the removal of α-LA from the silica nanoparticles (LNS-1 NPs) resulted in the composite of enlarged pore size with negligible bactericidal activities. Notably, the Isoniazide (INH) and Rifampicin (RIF)-encapsulated LNS NPs exhibited outstanding antimycobacterial activity against both drug-sensitive and drug-resistant Mycobacterium tuberculosis (M. tuberculosis). The obtained highly biocompatible, biosafe and low-energy consumptive α-LA-contained mesostructured silica-based bactericide holds promising therapeutic potentials to tackle the emerging drug-resistant infectious microbes.
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http://dx.doi.org/10.1016/j.ejps.2022.106261DOI Listing
September 2022

Chromosome-scale genome assembly of Rhododendron molle provides insights into its evolution and terpenoid biosynthesis.

BMC Plant Biol 2022 Jul 15;22(1):342. Epub 2022 Jul 15.

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, NHC Key Laboratory of Biosynthesis of Natural Products, CAMS Key Laboratory of Enzyme and Biocatalysis of Natural Drugs, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Xian Nong Tan Street, Beijing, 100050, China.

Background: Rhododendron molle (Ericaceae) is a traditional Chinese medicine, which has been used to treat rheumatism and relieve pain since ancient times. The characteristic grayanoids of this plant have been demonstrated to be the chemical basis for the analgesic activity. Moreover, unlike morphine, these diterpenoids are non-addictive. Grayanoids mainly distribute in the leaves, flowers, roots, and fruits of R. molle, with low content. Currently the research on the biosynthesis of grayanoids is hindered, partially due to lack of the genomic information.

Results: In the present study, a total of 744 Mb sequences were generated and assembled into 13 chromosomes. An ancient whole-genome duplication event (Ad-β) was discovered that occurred around 70 million years ago. Tandem and segmental gene duplications led to specific gene expansions in the terpene synthase and cytochrome P450 (CYP450) gene families. Two diterpene synthases were demonstrated to be responsible for the biosynthesis of 16α-hydroxy-ent-kaurane, the key precursor for grayanoids. Phylogenetic analysis revealed a species-specific bloom of the CYP71AU subfamily, which may involve the candidate CYP450s responsible for the biosynthesis of grayanoids. Additionally, three putative terpene biosynthetic gene clusters were found.

Conclusions: We reported the first genome assembly of R. molle and investigated the molecular basis underpinning terpenoids biosynthesis. Our work provides a foundation for elucidating the complete biosynthetic pathway of grayanoids and studying the terpenoids diversity in R. molle.
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http://dx.doi.org/10.1186/s12870-022-03720-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9284817PMC
July 2022

Association of Maternal Betaine-Homocysteine Methyltransferase (BHMT) and BHMT2 Genes Polymorphisms with Congenital Heart Disease in Offspring.

Reprod Sci 2022 Jul 14. Epub 2022 Jul 14.

Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China.

To systematically explore the association of single nucleotide polymorphisms (SNPs) of maternal BHMT and BHMT2 genes with the risk of congenital heart disease (CHD) and its three subtypes including atrial septal defect (ASD), ventricular septal defect (VSD), and patent ductus arteriosus (PDA) in offspring. A hospital-based case-control study involving 683 mothers of CHD children and 740 controls was performed. Necessary exposure information was captured through epidemiological investigation. Totally twelve SNPs of maternal BHMT and BHMT2 genes were detected and analyzed systematically. The study showed that maternal BHMT gene polymorphisms at rs1316753 (CG vs. CC: OR = 1.96 [95% CI 1.41-2.71]; GG vs. CC: OR = 1.99 [95% CI 1.32-3.00]; dominant model: OR = 1.97 [95% CI 1.44-2.68]) and rs1915706 (TC vs. TT: OR = 1.93 [95% CI 1.44-2.59]; CC vs. TT: OR = 2.55 [95% CI 1.38-4.72]; additive model: OR = 1.77 [95% CI 1.40-2.24]) were significantly associated with increased risk of total CHD in offspring. And two haplotypes were observed to be significantly associated with risk of total CHD, including C-C haplotype involving rs1915706 and rs3829809 in BHMT gene (OR = 1.30 [95% CI 1.07-1.58]) and C-A-A-C haplotype involving rs642431, rs592052, rs626105, and rs682985 in BHMT2 gene (OR = 0.71 [95% CI 0.58-0.88]). Besides, a three-locus model involving rs1316753 (BHMT), rs1915706 (BHMT), and rs642431 (BHMT2) was identified through gene-gene interaction analyses (P < 0.01). As for three subtypes including ASD, VSD, and PDA, significant SNPs and haplotypes were also identified. The results indicated that maternal BHMT gene polymorphisms at rs1316753 and rs1915706 are significantly associated with increased risk of total CHD and its three subtypes in offspring. Besides, significant interactions between different SNPs do exist on risk of CHD. Nevertheless, studies with larger sample size in different ethnic populations and involving more SNPs in more genes are expected to further define the genetic contribution underlying CHD and its subtypes.
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http://dx.doi.org/10.1007/s43032-022-01029-3DOI Listing
July 2022

Dispersion and Preparation of Nano-AlN/AA6061 Composites by Pressure Infiltration Method.

Nanomaterials (Basel) 2022 Jun 30;12(13). Epub 2022 Jun 30.

Departmentof Materials Science and Engineering, Harbin Institute of Technology, Harbin 150001, China.

Nanomaterials play an important role in metal matrix composites (MMC). In this study, 3.0 wt.%, 6.0 wt.%, and 9.0 wt.% nano-AlN-particles-reinforced AA6061 (nano-AlN/AA6061) composites were successfully prepared by pressure infiltration technique and then hot extruded (HE) at 500 °C. The microstructural characterization of the composites after HE show that the grain structure of the Al matrix is significantly refined, varying from 2 to 20 μm down to 1 to 3 μm. Nano-AlN particles in the composites are agglomerated around the matrix, and the distribution of nano-AlN is improved after HE. The interface between AA6061 and nano-AlN is clean and smooth, without interface reaction products. The 3.0 wt.% nano-AlN/AA6061 composite shows an uppermost yield and supreme tensile strength of 333 MPa and 445 MPa, respectively. The results show that the deformation procedure of the composite is beneficial to the further dispersion of nano-AlN particles and improves the strength of nano-AlN/AA6061 composite. At the same time, the strengthening mechanism active in the composites was discussed.
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http://dx.doi.org/10.3390/nano12132258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9268184PMC
June 2022

Optimization of the electrodeposition process of a polypyrrole/multi-walled carbon nanotube fiber electrode for a flexible supercapacitor.

RSC Adv 2022 Jun 21;12(28):18134-18143. Epub 2022 Jun 21.

School of Instruments and Electronics, North University of China Taiyuan 030051 China.

In the large-scale production of flexible supercapacitors, given the poor interface stability and the low mass loading of functional films on the fiber electrode, cyclic voltammetry (CV) and constant current (CC) electrodeposition methods were adopted to prepare polypyrrole/multi-walled carbon nanotubes (PPy/MWCNTs) on the surface of polyacrylonitrile (PAN) carbon cloth to explore the optimization process. The surface morphology and structural properties of the flexible electrode were characterized, and the electrical and electrochemical properties were studied. The research indicated that the PPy/MWCNTs were uniformly distributed on the fiber surface in the form of a linear structure and were amorphous and rich in carbon, nitrogen, and oxygen functional groups. A higher deposition current density helped improve the degree of coating of the MWCNTs with PPy and the number of oxygen-containing functional groups. The electrical and electrochemical properties of the flexible electrode prepared using the CC method were excellent; the electrochemical properties of the samples in the bent state were not significantly different from those in the straightened state. Using CC and CV methods, the conductivities of the samples were 32.4 S cm and 24.1 S cm, the area-specific capacitance values were 96.24 mF cm and 46.18 mF cm at a scan rate of 100 mV s, the equivalent series resistance values were 2.74 Ω and 4.67 Ω, the specific capacitance retention rates were 94.4% and 88.3% after 1000 cycles, and the capacitance retention rates were 89.7% and 80.6% after 5000 cycles, respectively. The differences in the performances of the flexible electrodes using the same preparation solvent and different preparation processes were due to the higher deposition current density of the CC method compared with that of CV. The former enhanced the polymerization degree of the PPy/MWCNT flexible electrode and improved the electrochemical performance. The presented research results are significant for the optimization of large-scale production processes.
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http://dx.doi.org/10.1039/d2ra02430fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9210518PMC
June 2022

[Lipid Droplets and Perilipins in Cardiovascular Diseases].

Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2022 Jun;44(3):463-471

Guangdong Cardiovascular Institute,Guangdong Provincial People's Hospital,Guangdong Academy of Medical Sciences,Guangzhou 510080,China.

Lipid droplet (LD) are multifunctional organelles which take part into intracellular lipid metabolism,mainly consisting of a neutral lipid core,a single-layer phospholipid shell,and LD-related protein (LRP).LRP on the shell can regulate the storage,transport,and metabolism of lipid.The imbalance of LD regulation could cause the abnormality of lipid metabolism,leading to the blood lipid changes and immune disorders.The available studies have demonstrated that LRP are capable of influencing the lipid metabolism in heart and atherosclerosis (AS) by regulating the physical processes in myocardial and vascular cells.This article reviewed the recent studies about LD in heart and vessels,and illustrated the effects of LD on myocardial cells,the formation of foam cells,and the development of atherosclerosis.Furthermore,we summarized the relationship between LD and cardiovascular diseases,providing new insights for the treatment of such diseases based on LD.
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http://dx.doi.org/10.3881/j.issn.1000-503X.14209DOI Listing
June 2022

Cryo-EM structures reveal the dynamic transformation of human alpha-2-macroglobulin working as a protease inhibitor.

Sci China Life Sci 2022 Jun 28. Epub 2022 Jun 28.

National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.

Human alpha-2-macroglobulin is a well-known inhibitor of a broad spectrum of proteases and plays important roles in immunity, inflammation, and infections. Here, we report the cryo-EM structures of human alpha-2-macroglobulin in its native state, induced state transformed by its authentic substrate, human trypsin, and serial intermediate states between the native and fully induced states. These structures exhibit distinct conformations, which reveal the dynamic transformation of alpha-2-macro-globulin that acts as a protease inhibitor. The results shed light on the molecular mechanism of alpha-2-macroglobulin in entrapping substrates.
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http://dx.doi.org/10.1007/s11427-022-2139-2DOI Listing
June 2022

Risk factors for habitual snoring among children aged 2-14 years in Chengdu, Sichuan.

Sleep Breath 2022 Jun 29. Epub 2022 Jun 29.

Department of Clinical Research Management, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Purpose: Habitual snoring (HS) is a prominent symptom of sleep-disordered breathing; thus, it is also important to consider the associated, multidimensional risk factors for HS in children. This study was aimed to identify risk factors for HS in children.

Methods: A cross-sectional survey was performed in Chengdu. Children aged 2-14 years from four districts were randomly chosen to participate. Questionnaires were voluntarily completed by the children's guardians.

Results: The survey included 926 boys and 622 girls, who were an average of 6.4 ± 3.0 years old. The sample included 463 habitual snorers (30.4%), 683 occasional snorers (44.8%), and 402 nonsnorers (26.4%). HS was found in 51.8% of children under 7 years old and 26.6% of children aged 7 years old or older. The prevalence of pregnancy complications was significantly lower in mothers who bore children with HS (p = .006). Among the HS group, 86.6% had an immediate family member who snores. Breastfeeding duration among the HS group was significantly less than among the occasional snoring and nonsnoring groups. History of symptoms of allergic rhinitis, rhinosinusitis, tonsillitis, and pneumonia/bronchitis in the past 6 months was associated with HS. Likewise, maternal smoking during pregnancy, maternal exposure to secondhand smoke during pregnancy, and child exposure to secondhand smoke were also associated with HS.

Conclusion: The prevalence of HS was higher in children under 7 years old. Having a mother with more education, a family history of snoring, a shorter period of breastfeeding, upper respiratory tract inflammation, and passive smoking are important risk factors for HS. Pregnancy complications may be associated with lower prevalence of snoring in childhood.
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http://dx.doi.org/10.1007/s11325-022-02670-7DOI Listing
June 2022

Decolorization of dark-colored waste cotton fabric using redox decoloring agents.

RSC Adv 2022 Jun 15;12(28):17689-17700. Epub 2022 Jun 15.

College of Textile & Clothing, Institute of Functional Textiles and Advanced Materials, State Key Laboratory of Bio-Fibers and Eco-Textiles, Collaborative Innovation Center of Marine Biomass Fibers Materials and Textiles of Shandong Province, Qingdao University Qingdao 266071 China

A huge quantity of dark-colored waste cotton fabrics with a high content of dye powder is dumped in landfills and incinerated, which is a waste of resources and pollutes the land and atmosphere. Also, it is meaningful to effectively strip the color from these dark-colored waste cotton fabrics with minimal damage to the strength of the textiles. In this study, a dark-colored waste cotton fabric dyed with reactive dyes was subjected to chemical treatment with redox decoloring agents. The effects of various treatments on the coloration and mechanical properties of the fabric were compared. This work developed an effective NaSO-HO system for decolorizing waste cotton fabric, with numerous advantages over conventional physicochemical approaches including achieving a CIE whiteness index of 74.1, tensile strength loss of 24.0%, weight loss of 1.2%, decoloration rate of 97.8%, and a degree of polymerization of 735.3. Furthermore, a mechanism was proposed to explain the two-step synergistic decolorization process.
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http://dx.doi.org/10.1039/d2ra02071hDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9198809PMC
June 2022

Predicting persistent organ failure on admission in patients with acute pancreatitis: development and validation of a mobile nomogram.

HPB (Oxford) 2022 Jun 6. Epub 2022 Jun 6.

Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Center and West China-Liverpool Biomedical Research Center, West China Hospital, Sichuan University, Chengdu, China. Electronic address:

Background: Early prediction of persistent organ failure (POF) is important for triage and timely treatment of patients with acute pancreatitis (AP).

Methods: All AP patients were consecutively admitted within 48 h of symptom onset. A nomogram was developed to predict POF on admission using data from a retrospective training cohort, validated by two prospective cohorts. The clinical utility of the nomogram was defined by concordance index (C-index), decision curve analysis (DCA), and clinical impact curve (CIC), while the performance by post-test probability.

Results: There were 816, 398, and 880 patients in the training, internal and external validation cohorts, respectively. Six independent predictors determined by logistic regression analysis were age, respiratory rate, albumin, lactate dehydrogenase, oxygen support, and pleural effusion and were included in the nomogram (web-based calculator: https://shina.shinyapps.io/DynNomapp/). This nomogram had reasonable predictive ability (C-indexes 0.88/0.91/0.81 for each cohort) and promising clinical utility (DCA and CIC). The nomogram had a positive likelihood ratio and post-test probability of developing POF in the training, internal and external validation cohorts of 4.26/31.7%, 7.89/39.1%, and 2.75/41%, respectively, superior or equal to other prognostic scores.

Conclusions: This nomogram can predict POF of AP patients and should be considered for clinical practice and trial allocation.
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http://dx.doi.org/10.1016/j.hpb.2022.05.1347DOI Listing
June 2022

ACPA-CD147 axis in the NLRP3 inflammasome of RA macrophages.

Cell Mol Immunol 2022 Aug 22;19(8):957-959. Epub 2022 Jun 22.

Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, PR China.

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http://dx.doi.org/10.1038/s41423-022-00889-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9338245PMC
August 2022

Complete secretion of recombinant Bacillus subtilis levansucrase in Pichia pastoris for production of high molecular weight levan.

Int J Biol Macromol 2022 Aug 15;214:203-211. Epub 2022 Jun 15.

College of Life Science and Technology, Guangxi University, 100 Daxue Road, Nanning, Guangxi 530004, China; State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, Guangxi University, 100 Daxue Road, Nanning, Guangxi 530004, China; Guangxi Research Center for Microbial and Enzyme Engineering Technology, 100 Daxue Road, Nanning, Guangxi 530004, China. Electronic address:

Three signal peptides from α-mating factor (α-MF), inulinase (INU) and native levansucrase (LS) were compared for secretion efficiency of Bacillus subtilis levansucrase SacB-T305A in Pichia pastoris GS115. The first complete secretion of bacterial levansucrase in yeasts under methanol induction was achieved while using α-MF signal. The secreted recombinant Lev(α-MF) proved to be glycosylated by combination of NanoLC-MS/MS and Endo H digestion. Interestingly, glycosylation not only improved significantly the polymerase thermostability, but also reversed the products profiles to favor synthesis of high molecular weight (HMW) levan which accounted for approximately 73 % to total levan-type polysaccharides. It indicated for the first time that the glycosylation of recombinant B. subtilis levansucrase affected significantly the products molecular weight distribution. It also provided a promising enzymatic way to effectively product HMW levan from sucrose resources.
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http://dx.doi.org/10.1016/j.ijbiomac.2022.06.092DOI Listing
August 2022

Follow-up contrast-enhanced ultrasonography of the carotidartery in patients with Takayasu arteritis: A retrospective study.

J Rheumatol 2022 Jun 15. Epub 2022 Jun 15.

Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, No. 127 Changle West Rd., Xi'an, 710032, Shaanxi, China; Department of Ultrasound, Xijing Hospital, Fourth Military Medical University, No. 127 Changle West Rd., Xi'an, 710032, Shaanxi, China. Jin Ding and Dangjie Wu contributed equally to this work. Funding: This study has received funding from Xijing Zhutui Project (XJZT19ML55) and the National Natural Science Foundation of China (Grant No: 81871273). Conflicts of interest: All authors declare no conflicts of interest. Corresponding author: Zhaohui Zheng, Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, No. 127 Changle West Rd., Xi'an, 710032, Shaanxi, China. Ping Zhu, Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, No. 127 Changle West Rd., Xi'an, 710032, Shaanxi, China.

Objective: The literature describing follow-up carotid contrast-enhanced ultrasonography (CEUS) is limited. We report our experience with monitoring CEUS performed in patients with Takayasu arteritis (TAK).

Methods: We retrospectively analyzed patients with TAK who had undergone carotid CEUS ≥2 times with a follow-up duration ≥12 months at Xijing Hospital between 2017 and 2020. We described how CEUS interpretation changed and recorded the state of imaging remission (CEUS visual grades of both sides ≤1) or relapse.

Results: In total, 106 patients with TAK and 425 CEUS visits were included (median followup: 25 months, interquartile range [IQR]: 18-30). The CEUS vascularization grade was significantly associated with the Kerr criteria (r=0.532, p<0.001), erythrocyte sedimentation rate (p<0.001), and C-reactive protein (p<0.001). At baseline, 76 patients (71.7%) had a CEUS active disease, and 30 had an inactive disease. The mid-term assessment (13 months, IQR: 10-16) showed that 29 CEUS-active patients (38.2%) achieved complete response, 34 (44.7%) achieved partial response, and 13 (17.1%) did not respond. At the last visit, the total number of responders was 78 (83.0%). CEUS relapse was observed in 28 (49.1%) patients, with a median of 16 (IQR: 10-21) months. The Kaplan-Meier curve demonstrated that the remission rate evaluated by the CEUS-combined method (median 22 months) was lower than that of the clinical-only evaluation (median, 11 months; p<0.001).

Conclusion: Response or relapse on CEUS was detected in most patients during followup. CEUS is an effective technique for detecting carotid artery inflammation in patients with TAK.
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http://dx.doi.org/10.3899/jrheum.220114DOI Listing
June 2022

Maturation of induced pluripotent stem cell-derived cardiomyocytes and its therapeutic effect on myocardial infarction in mouse.

Bioact Mater 2023 Feb 4;20:286-305. Epub 2022 Jun 4.

The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China.

Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have an irreplaceable role in the treatment of myocardial infarction (MI), which can be injected into the transplanted area with new cardiomyocytes (Cardiomyocytes, CMs), and improve myocardial function. However, the immaturity of the structure and function of iPSC-CMs is the main bottleneck at present. Since collagen participates in the formation of extracellular matrix (ECM), we synthesized nano colloidal gelatin (Gel) with collagen as the main component, and confirmed that the biomaterial has good biocompatibility and is suitable for cellular in vitro growth. Subsequently, we combined the PI3K/AKT/mTOR pathway inhibitor BEZ-235 with Gel and found that the two combined increased the sarcomere length and action potential amplitude (APA) of iPSC-CMs, and improved the Ca processing ability, the maturation of mitochondrial morphological structure and metabolic function. Not only that, Gel can also prolong the retention rate of iPSC-CMs in the myocardium and increase the expression of Cx43 and angiogenesis in the transplanted area of mature iPSC-CMs, which also provides a reliable basis for the subsequent treatment of mature iPSC-CMs.
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http://dx.doi.org/10.1016/j.bioactmat.2022.05.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9167678PMC
February 2023

Association of the Weight-Adjusted-Waist Index With Risk of All-Cause Mortality: A 10-Year Follow-Up Study.

Front Nutr 2022 25;9:894686. Epub 2022 May 25.

Department of Geriatrics, the 2nd Medical Center, Chinese PLA General Hospital, Beijing, China.

Background: To explore the relationship between weight-adjusted-waist index (WWI) and the risk of all-cause mortality in one urban community-dwelling population in China.

Methods: This is a prospective cohort study with a sample of 1,863 older adults aged 60 years or over in Beijing who completed baseline examinations in 2009-2010 and a 10-year follow-up in 2020. WWI was calculated as waist circumference (cm) divided by the square root of weight (kg). Cox regression analysis was performed to investigate the significance of the association of WWI with all-cause mortality. The area under the receiver operating characteristic (ROC) curves were used to compare the ability of each obesity index to predict mortality.

Results: During a median follow-up of 10.8 years (1.0 to 11.3 years), 339 deaths occurred. After adjusted for covariates, the hazard ratios (HRs) for all-cause mortality progressively increased across the tertile of WWI. Compared with the lowest WWI category (tertile1 <10.68 cm/√kg), with WWI 10.68 to 11.24cm/√kg, and≥11.25 cm/√kg, the HRs (95% confidence intervals (CIs)) for all-cause mortality were 1.58 (1.12-2.22), and 2.66 (1.80-3.92), respectively. In stratified analyses, the relationship between WWI and the risk of all-cause mortality persisted. The area under ROC for WWI was higher for all-cause mortality than BMI, WHtR, and WC.

Conclusion: WWI was associated with a higher risk for all-cause mortality, and the association was more robust with the highest WWI category.
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http://dx.doi.org/10.3389/fnut.2022.894686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174751PMC
May 2022

Enhancing the Strengthening Effect of Graphene-Nanoplates in Al Matrix Composites by Heterogeneous Matrix Design.

Nanomaterials (Basel) 2022 May 27;12(11). Epub 2022 May 27.

Department of Material Science and Engineering, Harbin Institute of Technology, Harbin 150001, China.

In the present work, the properties of graphene-nanoplates/aluminum (GNPs/Al) composites with a heterogeneous matrix design were investigated. The advantage of the heterogeneous matrix was investigated by the finite element method. Then, 0.6 wt.% (GNPs/6061Al)/2024Al (heterogeneous matrix) and 0.6 wt.% GNPs/6061Al composites were prepared by ball milling, pressure infiltration technology, and hot extrusion. The aggregation of GNPs was eliminated and the interlayer slide of GNPs was observed. Mechanical property test results show that the mechanical properties of the heterogeneous matrix composite are better than that of a homogeneous matrix composite, including strength, elastic modulus, and plasticity. It is assumed that the heterogeneous matrix design enhances the non-uniform stress field during the deformation treatment. This improves the dispersion of GNPs, grain refinement, and produces the few-layer graphene (FLG), thus enhancing the strengthening effect of GNPs. Meanwhile, heterogeneous matrix design is thought to introduce more hardening mechanisms to increase the plasticity of materials and improve the intrinsic trade-off of strength and toughness.
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http://dx.doi.org/10.3390/nano12111833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9182204PMC
May 2022

Integrative Analysis of the Genomic and Immune Microenvironment Characteristics Associated With Clear Cell Renal Cell Carcinoma Progression: Implications for Prognosis and Immunotherapy.

Front Immunol 2022 23;13:830220. Epub 2022 May 23.

Department of Urology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Unlike early clear cell renal cell carcinoma (ccRCC), locally advanced and metastatic ccRCC present poor treatment outcomes and prognosis. As immune checkpoint inhibitors have achieved favorable results in the adjuvant treatment of metastatic ccRCC, we aimed to investigate the immunogenomic landscape during ccRCC progression and its potential impact on immunotherapy and prognosis. Using multi-omics and immunotherapy ccRCC datasets, an integrated analysis was performed to identify genomic alterations, immune microenvironment features, and related biological processes during ccRCC progression and evaluate their relevance to immunotherapy response and prognosis. We found that aggressive and metastatic ccRCC had higher proportions of genomic alterations, including mutations, Del(14q), Del(9p), and higher immunosuppressive cellular and molecular infiltration levels. Of these, the Del(14q) might mediate immune escape in ccRCC the VEGFA-VEGFR2 signaling pathway. Furthermore, immune-related pathways associated with ccRCC progression did not affect the immunotherapeutic response to ccRCC. Conversely, cell cycle pathways not only affected ccRCC progression and prognosis, but also were related to ccRCC immunotherapeutic response resistance. Overall, we described the immunogenomic characteristics of ccRCC progression and their correlations with immunotherapeutic response and prognosis, providing new insights into their prediction and the development of novel therapeutic strategies.
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http://dx.doi.org/10.3389/fimmu.2022.830220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9168804PMC
May 2022

Multiple optimizations of recombinant plasmid for improving expression of Hepatitis B core antigen in Escherichia coli.

Protein Expr Purif 2022 10 3;198:106127. Epub 2022 Jun 3.

YishengBio Co., Ltd., Beijing, 102629, China. Electronic address:

Hepatitis B core antigen (HBcAg) can self-assemble into virus-like particles (VLPs) when expressed in Escherichia coli. We optimized the different of the expression plasmid pBV220, including the ribosome bind site (RBS), spacer region, promoter and replication origin (ori), as well as the hbc gene dosage, to enhance HBcAg transcription and translation in E. coli. The optimized construct with a customized RBS6, 6 nt spacer, T7 promoter and pUCori significantly increased the levels of HBc36GFP fusion protein to 3.4-folds compared to the control. Thereafter, we substituted hbc36gfp gene with different copies of the hbc gene and tested the effects of gene dosage on HBcAg expression. The HBcAg-VLPs yield obtained using an engineered strain with three copies of hbc was 842.1 ± 46.8 μg/mL, which was 2.2-folds higher compared to that in the control strain. Thus, our study provides a simple and effective strategy for improving HBcAg expression in E. coli. Since the HBcAg-VLPs are promising carriers for presenting foreign antigen epitopes, an in vitro expression system that can generate high levels of HBcAg-VLPs can serve as a promising tool for developing novel HBV vaccines and drugs.
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http://dx.doi.org/10.1016/j.pep.2022.106127DOI Listing
October 2022
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