Publications by authors named "Jingjing Wang"

1,019 Publications

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The immune cell landscape of peripheral blood mononuclear cells from PNS patients.

Sci Rep 2021 Jun 22;11(1):13083. Epub 2021 Jun 22.

Department of clinical laboratory, The Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Road, Hangzhou, 310003, Zhejiang, China.

Existing research suggests that the human immune system and immune cells are involved in the pathogenesis of nephrotic syndrome, but there is still a lack of direct evidence. This study tried to analyze the profiling of immune cells in the peripheral blood of steroid-sensitive nephrotic syndrome (SSNS) patients and steroid-resistant nephrotic syndrome (SRNS) patients before and after standard steroid treatment to clarify the immunological mechanism of nephrotic syndrome patients. The number and proportion of CD4 + T cells in patients with nephrotic syndrome remained unchanged. However, there is an imbalance of Th1 and Th2 and an excessive increase of Th17 cells. The number of CD8 + T cells and the number of effector CD8 + T cells in them increased significantly, but only in SSNS, the number of activated CD8 + T cells increased, and the number of activated T cells decreased significantly. Nephrotic syndrome patients also have B cell disorder, and it is more prominent in SSNS patients. Compared with the normal control, only the number of B cells and plasmablast in SSNS patients increased significantly (Z = - 2.20, P = 0.028). This study also observed that transitional B cells decreased in both SSNS and SRNS patients, but SSNS patients' decrease was lower than in SRNS patients. Compared with normal controls, monocytes in patients with nephrotic syndrome decreased significantly. The main reason was that Non-classical Monocyte decreased, while Classical Monocyte increased slightly. The total number of NK cells did not change, but the internal cell subgroups' composition occurred. Changes, realized as CD56hi NK cells increased, CD56low NK cells decreased; and the above trend is more evident in SSNS patients. Patients with nephrotic syndrome have immune disorders, including T cells, B cells, Monocytes, and NK cells. It can be confirmed that immune factors are involved in the pathogenesis of the nephrotic syndrome.
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http://dx.doi.org/10.1038/s41598-021-92573-6DOI Listing
June 2021

Elemental fingerprints in natural nanomaterials determined using SP-ICP-TOF-MS and clustering analysis.

Sci Total Environ 2021 Jun 15;792:148426. Epub 2021 Jun 15.

Department of Civil and Environmental Engineering, College of Engineering and Computing, University of South Carolina, SC 29208, USA. Electronic address:

Detection and quantification of engineered nanomaterials in environmental systems require precise knowledge of the elemental composition, association, and ratios in homologous natural nanomaterials (NNMs). Here, we characterized soil NNMs at the single particle level using single particle-inductively coupled plasma-time of flight-mass spectrometer (SP-ICP-TOF-MS) in order to identify the elemental purity, composition, associations, and ratios within NNMs. Elements naturally present as a major constituent in NNMs such as Ti, and Fe occurred predominantly as pure/single metals, whereas elements naturally present at trace levels in NNMs occurred predominantly as impure/multi-metal NNMs such as V, Nb, Pr, Nd, Sm, Eu, Gd, Tb, Er, Dy, Yb, Lu, Hf, Ta, Pb, Th, and U. Other elements occurred as a mixture of single metal and multi-metal NNMs such as Al, Si, Cr, Mn, Ni, Cu, Zn, Ba, La, Ce, W, and Bi. Thus, elemental purity can be used to differentiate ENMs vs. NNMs only for those elements that occur at trace level in NNMs. We also classified multi-metal NNM into clusters of similar elemental composition and determined their mean elemental composition. Six major clusters accounted for more than 95% of the detected multi-metal NNMs including Al-, Fe-, Ti-, Si-, Ce-, and Zr-rich particles' clusters. The elemental composition of these multi-metal NNM clusters is consistent with naturally occurring minerals. Titanium occurred as a major element (>70% of the total metal mass in NNMs) in Ti-rich cluster and as a minor (<25% of the total metal mass in NNMs) element in likely clay, titanomagnetite, and aluminum oxide phases. Two rare earth element (REE) clusters were identified, characteristic of light REEs and heavy REEs. The findings of this study provide a methodology and baseline information on the elemental composition, associations, and ratios of NNMs, which can be used to differentiate NNMs vs. ENMs in environmental systems.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148426DOI Listing
June 2021

Photoactive Silver Nanoagents for Backgroundless Monitoring and Precision Killing of Multidrug-Resistant Bacteria.

Nanotheranostics 2021 1;5(4):472-487. Epub 2021 Jun 1.

State Key Laboratory of Medicinal Chemical Biology, Research Center for Analytical Sciences, Tianjin Key Laboratory of Biosensing and Molecular Recognition, College of Chemistry, Nankai University, Tianjin 300071, China.

The growing prevalence of multidrug-resistant (MDR) bacteria makes it clinically urgent to develop an agent able to detect and treat infections simultaneously. Silver has served as a broad-spectrum antimicrobial since ancient times but suffers from major challenges such as moderate antimicrobial activity, nonspecific toxicity, and difficulty to be visualized . Here, we propose a new photoactive silver nanoagent that relies on a photosensitizer-triggered cascade reaction to liberate Ag on bacterial surfaces exclusively, allowing the precise killing of MDR bacteria. Additionally, the AgNP core acts as a backgroundless surface-enhanced Raman scattering (SERS) substrate for imaging the distribution of the nanoagents on bacterial surfaces and monitoring their metabolic dynamics in the infection sites. In this strategy, the photoactive antibacterial AgNP was decorated with photosensitizers (Chlorin e6, Ce6) and Raman reporter (4-Mercaptobenzonitrile, 4-MB) to provide new opportunities for clinically monitoring and fighting MDR bacterial infections. Upon 655 nm laser activation, the Ce6 molecules produce ROS efficiently, triggering the rapid release of Ag from the AgNP core to kill bacteria. Poly[4-O-(α-D-glucopyranosyl)-D-glucopyranose] (GP) was introduced as bacteria-specific targeting ligands. SERS spectra of the prepared GP-Ce6/MB-AgNPs were recorded after injecting for 0.5, 4, 8, 12, 24, and 48 h to track the dynamic metabolism of the nanoagents and thus guiding the antibacterial therapy. This new antimicrobial strategy exerts a dramatically enhanced antibacterial activity. The antibacterial efficiencies of this non-antibiotic technique were up to 99.6% against Methicillin-resistant Staphylococcus aureus (MRSA) and 98.8% against Escherichia coli (EC), while the antibacterial efficiencies for MRSA- and Carbapenem-resistant Pseudomonas aeruginosa (CRPA)-infected mice models were 96.8% and 93.6%, respectively. Besides, backgroundless SERS signal intensity of the wound declined to the level of normal tissue until 24 h, indicating that the nanoagents had been completely metabolized from the infected area. Given the backgroundless monitoring ability, high antibacterial efficacy, and low toxicity, the photoactive cascading agents would hold great potential for MDR-bacterial detection and elimination in diverse clinical settings.
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http://dx.doi.org/10.7150/ntno.62364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210445PMC
June 2021

Primitive neuroectodermal tumor of the pericardium: a case report and literature review.

BMC Cardiovasc Disord 2021 Jun 16;21(1):305. Epub 2021 Jun 16.

Department of Radiology, The First Medical Center of Chinese, PLA General Hospital, No.28 Fuxing Street of Haidian District, Beijing, 100853, China.

Background: The primitive neuroectodermal tumors (PNETs) are a family of highly malignant tumors with a multidirectional differential potential. The tumors are characterized by aggressive small round tumor cells that originate from the spinal cord of the central and sympathetic nervous systems. Cases involving the pericardium are extremely rare. Herein, we present a case of peripheral primitive neuroectodermal tumor (pPNET) that originated in the pericardium.

Case Presentation: A 23-year-old woman presented with cough and progressive dyspnea for 1 month, followed by eyelid and facial edema for 10 days, without any apparent cause. Significantly elevated tumor markers were detected in her blood. A cardiac ultrasound revealed a 74 mm × 61 mm spherical mass that was attached to the left pericardium, as well as massive pericardial effusion. Positron emission tomography-CT (PET-CT) showed focal hypermetabolism in the left pericardium. Via histopathology and immunohistochemistry, the spherical mass was identified as PNETS. The patient was successfully treated with a combination of surgical resection via thoracotomy and postoperative chemotherapy, and she was disease-free for 7 years at follow-up. Unfortunately, at 7 years after the treatment, the patient's pPNET recurred. Positron emission tomography-MRI (PET-MRI) and 64-slice coronary CTA revealed that the aorta and multiple coronary arteries were involved. Subsequently, the patient refused a heart transplant and voluntarily left the hospital.

Conclusions: This paper reports on a rare and recurrent case of PNET in the parietal pericardium. With respect to the different biologic characteristics and prognoses of pPNETs (compared to other known pericardium tumors), it is essential to consider this entity as a differential diagnosis in pericardium tumors.
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http://dx.doi.org/10.1186/s12872-021-02113-3DOI Listing
June 2021

A Phase I, Randomized, Single-Dose Study to Evaluate the Biosimilarity of HOT-3010 to Adalimumab Among Healthy Chinese Male Subjects.

Front Pharmacol 2021 17;12:646171. Epub 2021 Mar 17.

Phase I Clinical Research Center, The First Hospital of Jilin University, Jilin, China.

This study explored the bioequivalence of a proposed biosimilar HOT-3010 vs. its reference product (adalimumab) among healthy Chinese male subjects. The study also investigated the tolerance, immunogenicity, and pharmacokinetics (PK). A randomized, double-blind, two-arm, parallel study was performed to examine the bioequivalence of HOT-3010 (40 mg) with that of adalimumab (Humira, AbbVie) as a reference drug. The study subjects were followed up for 71 days. PK properties exhibited by HOT-3010 ( = 66) and adalimumab ( = 68) groups were similar. The 90% confidence intervals of the ratios for , AUC , and AUC were observed to be in the range 80-125% on comparing the two groups. For anti-drug antibodies (ADA), the number of subjects found to be positive in the HOT-3010 group and adalimumab group were 29 (43.94%) and 32 (47.06%), whereas 27 (40.91%) and 27 (39.71%) subjects were found to be positive for NAb, respectively. Treatment-related treatment-emergent adverse events (TEAEs) were recorded in 32 subjects each in both the groups, respectively. The PK characteristics and immunogenicity exhibited by HOT-3010 were similar to that of the reference product, adalimumab. The safety profiles were similar in both the treatment groups with mild-moderate adverse effects.
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http://dx.doi.org/10.3389/fphar.2021.646171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190825PMC
March 2021

MiR-15b weakens proliferation and enhances apoptosis of melanoma cells through targeting ABCG2 signaling pathway.

Panminerva Med 2021 Jun 11. Epub 2021 Jun 11.

Department of Burn Orthopedic Surgery, Fourth Medical Center of PLA General Hospital, Beijing, China -

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http://dx.doi.org/10.23736/S0031-0808.21.04415-3DOI Listing
June 2021

Bacillus amyloliquefaciens FH-1 significantly affects cucumber seedlings and the rhizosphere bacterial community but not soil.

Sci Rep 2021 Jun 8;11(1):12055. Epub 2021 Jun 8.

Tianjin Key Laboratory for Industrial Biological Systems and Bioprocessing Engineering, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, People's Republic of China.

Plant growth-promoting bacteria (PGPB) inoculants have been applied worldwide. However, the ecological roles of PGPB under different soil conditions are still not well understood. The present study aimed to explore the ecological roles of Bacillus amyloliquefaciens FH-1 (FH) on cucumber seedlings, rhizosphere soil properties, and the bacterial community in pot experiments. The results showed that FH had significant effects on cucumber seedlings and the rhizosphere bacterial community but not on soil properties. The FH promoted cucumber seedlings growth, reduced the rhizosphere bacterial diversity, increased Proteobacteria, and decreased Acidobacteria. Linear discriminant analysis (LDA) effect size (LEfSe) revealed that FH enriched two taxa (GKS2_174 and Nannocystaceae) and inhibited 18 taxa (mainly Acidobacteria, Actinobacteria, BRC1, Chloroflexi, Plantctomycetes, and Verrucomicrobia). Co-occurrence network analysis demonstrated that FH increased bacteria-bacteria interactions and that Bacillus (genus of FH) had few interactions with the enriched and inhibited taxa. This might indicate that FH does not directly affect the enriched and inhibited taxa. Correlation analysis results displayed that cucumber seedlings' weight and height/length (except root length) were significantly correlated with the 18 inhibited taxa and the enriched taxa Nannocystaceae. It was speculated that FH might promote cucumber seedling growth by indirectly enriching Nannocystaceae and inhibiting some taxa from Acidobacteria, Actinobacteria, BRC1, Chloroflexi, Plantctomycetes, and Verrucomicrobia.
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http://dx.doi.org/10.1038/s41598-021-91399-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187646PMC
June 2021

Intracellular Ca2+ signaling and ORAI calcium release-activated calcium modulator 1 (ORAI1) are associated with hepatic lipidosis in dairy cattle.

J Anim Sci 2021 Jun 8. Epub 2021 Jun 8.

College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang, China.

Fatty liver is a common metabolic disorder afflicting dairy cows during the periparturient period and is closely associated with endoplasmic reticulum (ER) stress. The onset of ER stress in humans and mice alters hepatic lipid metabolism, but it is unknown if such event contributes to fatty liver in dairy cows soon after parturition. ORAI1 is a key component of the store-operated Ca2+ entry mechanism regulating cellular Ca2+ balance. The purpose of this study was to investigate the role of ORAI1 on hepatic lipidosis via ER stress in dairy cows. Liver tissue biopsies were collected from Holstein cows diagnosed as healthy (n=6) or with hepatic lipidosis (n=6). Protein and mRNA abundance of ER stress-related targets, lipogenic targets or the transcription regulator SREBP1 and ORAI1 were greater in cows with lipidosis. In vitro, hepatocytes were isolated from four healthy female calves and used for culture with a 1.2 mM mixture of fatty acids (oleic, linoleic, palmitic, stearic, and palmitoleic acid) for various times (0, 3, 6, 9 or 12 h). As incubation time progressed, increases in concentration of Ca2+ and abundance of protein kinase RNA-like ER kinase (PERK), inositol requiring protein-1α (IRE1α), and activating transcription factor-6 (ATF6) protein in response to exogenous fatty acids underscored a mechanistic link among Ca2+, fatty acids and ER stress. In a subsequent study, hepatocytes were transfected with small interfering RNA (siORAI1) or the ORAI1 inhibitor BTP2 for 48 h or 2 h followed by a challenge with the 1.2 mM mixture of fatty acids for 6 h. Compared with control group, silencing or inhibition of ORAI1 led to decreased abundance of fatty acid synthesis (FASN, SREBP1 and ACACA) and ER stress-related proteins in bovine hepatocytes. Overall, data suggested that NEFA through ORAI1 regulate intracellular Ca2+ signaling, induce ER stress, and lead to lipidosis in isolated hepatocytes.
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http://dx.doi.org/10.1093/jas/skab184DOI Listing
June 2021

Copper Peroxide-Loaded Gelatin Sponges for Wound Dressings with Antimicrobial and Accelerating Healing Properties.

ACS Appl Mater Interfaces 2021 Jun 7;13(23):26800-26807. Epub 2021 Jun 7.

State Key Laboratory of Applied Organic Chemistry, Institute of Biochemical Engineering & Environmental Technology, College of Chemistry and Chemical Engineering, Lanzhou University, 222 Tianshui Road, Lanzhou 730000, P. R. China.

Catalytic conversion of hydrogen peroxide (HO) to more toxic hydroxyl radicals (OH) is a good choice for sterilization and anti-infection, but endogenous HO is insufficient to achieve satisfactory sterilization efficacy. Despite great efforts, designing and developing antimicrobial materials that specifically and effectively self-supply HO at the wound site remain as tremendous challenges. Here, we report a pH-responsive copper peroxide-loaded wound dressing made from copper hydroxide and gelatin sponge and then reacted with HO. In vitro experiments show that the prepared wound dressing has good bactericidal properties against (), (), and (). Moreover, the as-prepared wound dressing can release OH specifically in the bacterial-infected skin wound, rather than in normal tissues, and in vivo skin wound-healing experiments proved that the synthesized copper peroxide-loaded gelatin sponge could combat effectively; in addition, Cu released from the gelatin sponge could stimulate angiogenesis and collagen deposition simultaneously. The study provides a strategy to improve antibacterial efficacy and reduce the toxic side effects through the release of OH by bacterial self-activation.
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http://dx.doi.org/10.1021/acsami.1c07409DOI Listing
June 2021

Hydrogel sunscreen based on yeast /gelatin demonstrates excellent UV-shielding and skin protection performance.

Colloids Surf B Biointerfaces 2021 May 29;205:111885. Epub 2021 May 29.

State Key Laboratory of Applied Organic Chemistry, Institute of Biochemical Engineering & Environmental Technology, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, PR China. Electronic address:

Traditional organic and inorganic sunscreens suffer from the disadvantages of low stability and poor biocompatibility. In the study, we developed a novel hydrogel sunscreen based on the yeast and gelatin, which demonstrated excellent UV protection property and broad absorption of UV across UVA and UVB region. Yeast was used as effective component and gelatin as matrix to fabricate the hydrogel, which is high hydrated and reasonable to simulate natural living tissue. As a common probiotic, yeast shows safety and satisfactory UV protection capability. Furthermore, the hydrogel sunscreen shows excellent biocompatibility and UV protection performance both in vitro and in vivo. Moreover, they can be prepared conveniently and provide an eco-friendly strategy, which provides experience and inspiration of probiotics in the cosmetics application.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111885DOI Listing
May 2021

Effect of liquid volume and microflora source on degradation rate and microbial community in corn stover degradation.

AMB Express 2021 Jun 1;11(1):80. Epub 2021 Jun 1.

Tianjin Key Laboratory for Industrial Biological Systems and Bioprocessing Engineering, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, No. 32, West 7th Avenue, Tianjin Airport Economic Area, Tianjin, 300308, P R China.

Degradation is the bottleneck in the utilization of crop straw. In this paper, we screened the microbial consortia degrading corn stover from straw degrading consortia MC1 (M), sheep feces (Y), and mixtures (Q) of M, Y, and cattle feces. The effects of microflora source and liquid volume (representing dissolved oxygen) on the microbial community and degradation rate of corn stover were investigated. The results showed that the degradation rate and cellulase activity of a 200 mL liquid volume (L2) were significantly higher than that of 100 mL (L1). Microflora source had a significant effect on bacterial and fungal diversity, composition and taxa. Q and Y had higher bacterial and fungal α-diversity than that of M. The degradation rate was significantly correlated with cellulase activity but not with microbial diversity. This indicated that liquid volume had a significant effect on degradation rate while microflora source had a significant effect on microbial community in corn stover degradation.
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http://dx.doi.org/10.1186/s13568-021-01233-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169732PMC
June 2021

Influence of the densities and nutritional components of bacterial colonies on the culture-enriched gut bacterial community structure.

AMB Express 2021 May 31;11(1):78. Epub 2021 May 31.

Xinxiang Key Laboratory of Pathogenic Biology, Department of Microbiology, School of Basic Medical Sciences, Xinxiang Medical University, 601 Jinsui Road, Hongqi District, Xinxiang, 453003, Henan, China.

Isolating relevant microorganisms is still a substantial challenge that limits the use of bacteria in the maintenance of human health. To confirm which media and which bacterial colony densities can enrich certain kinds of bacteria, we selected eight common media and used them to enrich the gut microorganisms on agar plates. Then, we calculated the numbers of bacterial colonies and collected the bacterial culture mixtures from each kind of medium. Using the Illumina HiSeq platform, we analyzed the composition and diversity of the culture-enriched gut bacterial community. Our data suggested that medium supplemented with blood could increase the diversity of the bacterial community. In addition, beef powder and peptone could significantly change the culture-enriched bacterial community. A moderate density (100-150 colony-forming units per plate) was optimal for obtaining the highest diversity on the agar. Similarly, membrane transport was significantly enriched in the moderate-density group, which indicated a more active metabolism in this density range. Overall, these results reveal the optimal culture conditions, including the densities of colonies and nutritional components for various gut bacteria, that provide a novel strategy for isolating bacteria in a way that is targeted and avoids blinded and repetitive work.
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http://dx.doi.org/10.1186/s13568-021-01240-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167003PMC
May 2021

Photodynamic inactivation of planktonic Staphylococcus aureus by sodium magnesium chlorophyllin and its effect on the storage quality of lettuce.

Photochem Photobiol Sci 2021 May 28. Epub 2021 May 28.

College of Food Science and Technology, Shanghai Ocean University, Shanghai, 201306, China.

Photodynamic inactivation (PDI) is a fast and effective non-heat sterilization technology. This study established an efficient blue light-emitting diode (LED) PDI with the photosensitizer sodium magnesium chlorophyllin (SMC) to eradicate Staphylococcus aureus in food. The antibacterial mechanisms were determined by evaluating DNA integrity, protein changes, morphological alteration, and the potency of PDI to eradicate S. aureus on lettuce was evaluated. Results showed that planktonic S. aureus could not be clearly observed on the medium after treatment with 5.0 μmol/L SMC for 10 min (1.14 J/cm). Bacterial cell DNA and protein were susceptible to SMC-mediated PDI, and cell membranes were found to be disrupted. Moreover, SMC-mediated PDI effectively reduced 8.31 log CFU/mL of S. aureus on lettuce under 6.84 J/cm radiant exposure (30 min) with 100 μmol/L SMC, and PDI displayed a potent ability to restrain the weight loss as well as retard the changes of color difference of the lettuce during 7 day storage. The study will enrich our understanding of the inactivation of S. aureus by PDI, allowing for the development of improved strategies to eliminate bacteria in the food industry.
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http://dx.doi.org/10.1007/s43630-021-00057-3DOI Listing
May 2021

Baseline Serum Cholesterol Levels Predict the Response of Patients with Advanced Non-Small Cell Lung Cancer to Immune Checkpoint Inhibitor-Based Treatment.

Cancer Manag Res 2021 18;13:4041-4053. Epub 2021 May 18.

Department of Radiation Oncology, Ningbo Medical Treatment Center Li Huili Hospital, Ningbo, 315040, People's Republic of China.

Purpose: Although predictive markers of immune checkpoint inhibitor (ICI)-based treatments have been extensively studied, with the exception of programmed death ligand 1 (PD-L1), most are not widely used in the clinic due to poor effects or defective practicability. The aim of this study was to identify those patients with high baseline serum cholesterol who benefit from ICI-based treatments.

Patients And Methods: Patients with advanced non-small cell lung cancer (NSCLC) treated at Ningbo Medical Center, Li Huili Hospital between August 2017 and December 2019 were enrolled in this retrospective study. The Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) were used to evaluate the efficacy of the ICI-based treatment. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier survival curves and compared using the log rank test. Univariate and multivariate analyses were conducted using the logistic regression analysis and Cox proportional hazards model. A receiver operating characteristic curve was created, and the area under the curve (AUC) was calculated to compare the predictive value of baseline serum cholesterol with PD-L1 expression for patient response to ICI-based treatment.

Results: In our cohort of 169 NSCLC patients, the objective response rate (ORR) and disease control rate (DCR) of the treatment were significantly higher in patients with hypercholesterolemia (>5.18 mmol/L) than in those with hypocholesterolemia (ORR: 33.67% vs 14.08%, P=0.004; DCR: 68.37% vs 42.25%, P=0.001). The median PFS was 7.9 months in the hypercholesterolemia group, significantly longer than in the hypocholesterolemia group (4.4 months, 95% CI: 4.620-7.380, P<0.001). The median OS in the two groups were 11 months and 8 months, with 95% CIs of 8.980-10.420 (P<0.001). The AUC for the baseline level of cholesterol was 0.706 (P<0.001), while it was 0.643 (P=0.001) for PD-L1 expression.

Conclusion: The baseline serum cholesterol level is predictive of a clinical benefit for advanced NSCLC patients who undergo ICI-based treatment, and hence it is a promising prognostic indicator for ICI-based treatment of NSCLC.
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http://dx.doi.org/10.2147/CMAR.S304022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140899PMC
May 2021

Activated phosphoinositide 3-kinase delta syndrome misdiagnosed as anti-neutrophil cytoplasmic antibody-associated vasculitis: a case report.

J Int Med Res 2021 May;49(5):3000605211013222

Department of Nephrology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.

Activated phosphoinositide 3-kinase delta syndrome (APDS) is a combined inborn error of immunity mainly caused by mutations. We herein describe a 4-year-old Chinese boy who was admitted for recurrent pneumonia and persistent hematuria and exhibited multisystem involvement and anti-neutrophil cytoplasmic antibody (ANCA) positivity. He was initially diagnosed with ANCA-associated vasculitis. However, genetic testing revealed a c.1574A>G mutation, resulting in a diagnosis of APDS1.
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http://dx.doi.org/10.1177/03000605211013222DOI Listing
May 2021

Creating Matched In vivo/In vitro Patient-Derived Model Pairs of PDX and PDX-Derived Organoids for Cancer Pharmacology Research.

J Vis Exp 2021 May 5(171). Epub 2021 May 5.

Crown Bioscience Inc., San Diego, CA, USA;

Patient-derived tumor xenografts (PDXs) are considered the most predictive preclinical models, largely believed to be driven by cancer stem cells (CSC) for conventional cancer drug evaluation. A large library of PDXs is reflective of the diversity of patient populations and thus enables population based preclinical trials ("Phase II-like mouse clinical trials"); however, PDX have practical limitations of low throughput, high costs and long duration. Tumor organoids, also being patient-derived CSC-driven models, can be considered as the in vitro equivalent of PDX, overcoming certain PDX limitations for dealing with large libraries of organoids or compounds. This study describes a method to create PDX-derived organoids (PDXO), thus resulting in paired models for in vitro and in vivo pharmacology research. Subcutaneously-transplanted PDX-CR2110 tumors were collected from tumor-bearing mice when the tumors reached 200-800 mm, per an approved autopsy procedure, followed by removal of the adjacent non-tumor tissues and dissociation into small tumor fragments. The small tumor fragments were washed and passed through a 100 µm cell strainer to remove the debris. Cell clusters were collected and suspended in basement membrane extract (BME) solution and plated in a 6-well plate as a solid droplet with surrounding liquid media for growth in a CO2 incubator. Organoid growth was monitored twice weekly under light microscopy and recorded by photography, followed by liquid medium change 2 or 3 times a week. The grown organoids were further passaged (7 days later) at a 1:2 ratio by disrupting the BME embedded organoids using mechanical shearing, aided by addition of trypsin and the addition of 10 µM Y-27632. Organoids were cryopreserved in cryo-tubes for long-term storage, after release from BME by centrifugation, and also sampled (e.g., DNA, RNA and FFPE block) for further characterization.
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http://dx.doi.org/10.3791/61382DOI Listing
May 2021

Efficacy and Safety of Combination Treatment With Apatinib and Osimertinib After Osimertinib Resistance in Epidermal Growth Factor Receptor-Mutant Non-small Cell Lung Carcinoma-A Retrospective Analysis of a Multicenter Clinical Study.

Front Mol Biosci 2021 5;8:639892. Epub 2021 May 5.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology, Peking University Cancer Hospital and Institute, Beijing, China.

Currently, there are limited treatment options for patients who developed resistance to osimertinib, a third-generation epidermal growth factor receptor (EGFR) inhibitor. Resistance to EGFR inhibitors is frequently associated with enhanced vascular endothelial growth factor (VEGF) levels. This multicenter, retrospective study aimed to evaluate the efficacy of the combination treatment with apatinib and osimertinib in 39 patients with EGFR-mutant non-small cell lung carcinoma (NSCLC) who developed osimertinib resistance. The patients received the combination of oral apatinib 250 mg qd and osimertinib 80 mg qd. The efficacy was evaluated after the first month then every 2 months thereafter. The primary endpoint was progression-free survival (PFS). The overall response rate (ORR) and the disease control rate (DCR) of the combination of apatinib and osimertinib was 12.8% (5/39) and 79.5% (31/39), respectively. The median PFS was 4 months [95% confidence interval (CI): 3.5-4.5 months]. Fourteen patients were administered with at least 6 months of combination therapy, and 11 of them remained on treatment programs. The 6-month PFS rate was 38%. Nine patients underwent biopsies after failing osimertinib treatment, and five of six patients with TP53 mutations had PFS of less than 3 months. The spectrum of resistance to osimertinib mechanisms included c-mesenchymal-epithelial transition factor (c-Met) amplification, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gain-of-function mutation, phosphatase and tensin homolog (PTEN) loss-of-function mutation, Erb-B2 receptor tyrosine kinase 2 (ERBB2) amplification, and insulin-like growth factor 1 receptor (IGF1R) mutation. The most common adverse events were hypertension (30.7%, 12/39), diarrhea (15.4%, 6/39), and proteinuria (12.8%, 5/39). The combination of apatinib and osimertinib improved the ORR and the DCR of patients with osimertinib-refractory EGFR-positive NSCLC, thus making it a reasonable treatment choice after the development of osimertinib resistance.
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http://dx.doi.org/10.3389/fmolb.2021.639892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131525PMC
May 2021

Real-Time Navigation System With Indocyanine Green Fluorescence for Sentinel Lymph Node Biopsy in Patients With Breast Cancer.

Front Oncol 2021 5;11:621914. Epub 2021 May 5.

Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, China.

Background: The naked-eye invisibility of indocyanine green fluorescence limits the application of near-infrared fluorescence imaging (NIR) systems for real-time navigation during sentinel lymph node biopsy (SLNB) in patients with breast cancer undergoing surgery. This study aims to evaluate the effectiveness and safety of a novel NIR system in visualizing indocyanine green fluorescence images in the surgical field and the application value of combined methylene blue (MB) and the novel NIR system in SLNB.

Methods: Sixty patients with clinical node-negative breast cancer received indocyanine green (ICG) and MB as tracers. Two NIR system instruments, namely, lymphatic fluorescence imaging system (LFIS) designed by the University of Science and Technology of China and vascular imager by Langfang Mingde Medical Biotechnology Co., Ltd. (Langfang vascular imager), were used as navigation assistance to locate sentinel lymph nodes (SLNs). Excising the lymph nodes developed by both MB and ICG by two NIR systems or palpably suspicious as SLNs and undergoing rapid pathological examination.

Results: Both instruments exhibited 95% (57/60) success for real-time lymphatic fluorescent images. A total of 186 SLNs were identified, of which two were pathologically confirmed as lacking any lymph node tissue. SLN identification rate was 100% (184/184) for MB plus LFIS and 86.96% (160/184) for MB alone. The median number of SLNs identified by LFIS combined with MB was 3 (range of 1-8), which was significantly higher than that by MB alone at 2 (range 1-7) (P<0.05).

Conclusion: LFIS effectively detects SLNs in breast cancer, projects the fluorescence signals during surgery, and provides a continuous surgical navigation system without the need for a remote monitor. The ICG method navigated by combined LFIS and MB may be a promising alternative tracer for radioisotope in SLN mapping.

Clinical Trial Registration: This clinical trial was registered with the China Clinical Trial Center, registration number ChiCTR2000039542.
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http://dx.doi.org/10.3389/fonc.2021.621914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133435PMC
May 2021

Bongkrekic acid induced neutrophil extracellular traps via p38, ERK, PAD4, and P2X1-mediated signaling.

Toxicol Appl Pharmacol 2021 07 19;423:115580. Epub 2021 May 19.

College of Life Sciences and Engineering, Foshan University, Foshan 528225, Guangdong Province, PR China. Electronic address:

Bongkrekic acid (BKA) produced by pseudomonas cocovenenans is a deadly toxin, and is mainly found in spoiled or fermented foods. However, less is known on its immunotoxicity. Neutrophil extracellular traps (NETs) are a novel effector mechanism of neutrophils against invading pathogens, but excessive NETs also contribute to tissue damage. This study aimed to investigate NET formation triggered by BKA in murine neutrophils, and describe its characteristics and potential mechanisms. Our results showed that BKA triggered NET formation via co-localization of DNA and histone or MPO by immunostaining. Moreover, BKA-triggered NET formation was dose- and time-dependent via NET quantification based on Picogreen-derived fluorescence intensities. Furthermore, BKA increased ROS production in neutrophils. Pharmacological inhibition indicated that BKA-triggered NET formation was associated with ROS-p38 and -ERK signaling pathways, but independent on NADPH oxidase. Besides, PAD4 and P2X1 receptor also mediated BKA-triggered NET formation. To our knowledge, all these findings provide for the first time an initial understanding of BKA on innate immunity, which might be helpful for further investigation on BKA immunotoxicity.
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http://dx.doi.org/10.1016/j.taap.2021.115580DOI Listing
July 2021

Gut Microbiota and Antitumor Immunity: Potential Mechanisms for Clinical Effect.

Cancer Immunol Res 2021 Apr;9(4):365-370

Program for Innovative Microbiome and Translational Research, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Several landmark preclinical studies have shown an association between the gut microbiota and the effectiveness of immunotherapy for cancer. These studies have sparked clinical trials aimed at modulating the gut microbiota in order to improve clinical response rates to immunotherapy. Despite this, the mechanisms through which the gut microbiota influences the effectiveness of immunotherapy are still incompletely characterized. Preclinical and preliminary clinical findings from numerous types of gut microbiota modulation studies, including fecal transplantation, probiotics, consortia, and diet, demonstrate that favorable microbiota modulation is associated with increased intratumoral infiltration of CD8 effector T cells. This CD8 T-cell infiltration is often associated with enhanced intratumoral activity of T-helper type 1 cells and dendritic cells and a lower density of immunosuppressive cells. Herein, we discuss how gut microbiota may affect the activity of immune cells by at least three interlacing mechanisms: activation of pattern recognition receptors, molecular mimicry, and impact of metabolites. We also discuss the therapeutic potential and limitations of the different gut microbiota modulation techniques and their putative mechanisms of immune activation.
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http://dx.doi.org/10.1158/2326-6066.CIR-20-0877DOI Listing
April 2021

[Study on the correlation between the content of bone morphogenetic protein 2 in demineralized bone matrix and its osteogenic activity and ].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 May;35(5):620-626

Shanghai Yapeng Biotechnology Co., Ltd, Shanghai, 201201, P.R.China.

Objective: To investigate the correlation between the content of bone morphogenetic protein 2 (BMP-2) in demineralized bone matrix (DBM) and its osteogenic activity and , in order to choose a simple and convenient method to evaluate the osteogenic activity of DBM.

Methods: The left mid-femoral tissues of 9 donors were taken, and DBMs (S1-S9) were prepared by dynamic decalcification process, and inactivated DBM (control group) was prepared at the same time. Protease inhibitor method, collagenase method, guanidine hydrochloride/ethylene diamine tetraacetic acid (EDTA) method, and RIPA lysate method were used to extract BMP-2 in S1-S9 and inactivated DBMs. The BMP-2 content was measured and the differences between DBMs were compared. Then the S1-S9 and inactivated DBMs were co-cultured with mouse embryonic osteoblasts MC3T3-E1, respectively. The cell proliferation was detected by MTT method and fluorescence staining, and alkaline phosphatase (ALP) activity was detected at the same time. Thirty BALB/c male nude mice were divided into 10 groups, namely S1-S9 DBM groups (S1-S9 groups) and inactivated DBM group (control group), with 3 mice in each group. Muscle pockets of the middle thighs were prepared on both hindlimbs of mice in each group, and implanted corresponding DBM materials. At 4 weeks after operation, the samples were taken for HE staining observation and semi-quantitative evaluation, and the new bone formation score was calculated.

Results: The BMP-2 content of DBM derived from different donor bones was distinct. The BMP-2 content obtained by different extraction methods for DBM prepared from the same donor bone was also different, and the extraction efficiency of the guanidine hydrochloride/EDTA method was the highest. cell experiments, MTT test displayed that cell proliferations and ALP activity were significantly higher in S4 and S6 groups than in other groups at each time point after co-cultivation ( <0.05). Moreover, the cell proliferation of S4 group was the most significant at 7 days ( <0.05); fluorescence staining demonstrated that the osteoblasts of each group was in good condition, but the osteoblasts of S1, S2, S3, S4, and S6 groups were significantly more than other groups. ectopic osteogenesis experiments, the cartilage and new bone formation could be seen in the bone graft area of S1-S6 groups at 4 weeks after operation, and with the increase of BMP-2 content, the more new bone formation induced by the material, the higher the score of new bone formation of the material ( <0.05). Among them, S4 and S6 groups contained a large number of chondrocytes and osteoblasts in the osteogenesis area.

Conclusion: The osteogenic activity of DBM can be evaluated through BMP-2 quantitative detection combined with osteoblast proliferation and differentiation experiments.
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http://dx.doi.org/10.7507/1002-1892.202012006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175199PMC
May 2021

Clinical and Genetic Features in 31 Serial Chinese Children With Gitelman Syndrome.

Front Pediatr 2021 29;9:544925. Epub 2021 Apr 29.

Department of Nephrology, The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, China.

Gitelman syndrome (GS, OMIM 263800) is a genetic congenital tubulopathy associated with salt loss, which is characterized by hypokalemic metabolic toxicity, hypocalciuria, and hypomagnesemia. GS, which is typically detected in adolescence or adulthood, has long been considered a benign tubular lesion; however, the disease is associated with a significant decrease in the quality of life. In this study, we assessed the genotype-phenotype correlations based on the medical histories, clinical symptoms, laboratory test results, and whole-exome sequencing profiles from pediatric patients with GS. Between January 2014 and December 2020, all 31 consecutively enrolled patients complained of fatigue, salt craving, and muscle weakness. Sixteen patients demonstrated growth retardation, and five patients presented with nocturia and constipation. All patients presented with hypokalemic metabolic alkalosis, normal blood pressure, hyperaldosteronism, and a preserved glomerular filtration rate, and 24 of the 31 (77.4%) patients had hypomagnesemia. Homozygous, compound heterozygous, and heterozygous mutations in were detected in 4, 24, and 3 patients, respectively. GS patients often present with muscle weakness and fatigue caused by hypokalemia and hypomagnesemia. Therefore, early diagnosis of GS is important in young children to reduce the possibility of growth retardation, tetany, and seizures. Next-generation sequencing such as whole-exome or whole-genome sequencing provides a practical tool for the early diagnosis and improvement of GS prognosis. Further whole-genome sequencing is expected to reveal more variants in among GS patients with single heterozygous mutations.
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http://dx.doi.org/10.3389/fped.2021.544925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116576PMC
April 2021

Case Report: Activating Mutation in Patients Presenting With Granulomatosis With Polyangiitis.

Front Immunol 2021 28;12:670312. Epub 2021 Apr 28.

Department of Rheumatology Immunology & Allergy, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.

Activated phosphoinositide 3-kinase δ syndrome (APDS) is an autosomal dominant primary immunodeficiency caused by gain-of-function (GOF) mutations in or genes. The phenotypes of APDS are highly variable, ranging from asymptomatic adults to profound immunodeficiency causing early death in childhood. Herein, we reported two pediatric patients with APDS presented with recurrent lung infections, sinusitis, hematuria, and positive anti-neutrophil cytoplasmic antibody (ANCA), previously diagnosed as granulomatosis with polyangiitis (GPA). Bronchoscopy showed mucosal nodule lymphoid hyperplasia in the entire airway. Many inflammatory cells infiltrated around the airway and in the lung parenchyma, and numbers of CD3 T cells and CD20 B cells were significantly increased, especially CD3+ T cells. Whole exome sequencing showed that they had the E1021K (c.3061 G >A) mutation in the gene. These are the first reported cases of APDS presenting as childhood-onset GPA. Pediatricians should suspect of APDS in the differential diagnosis of children who present with GPA-like symptoms. Additionally, timely and repeated bronchoscopies could contribute to providing an important diagnostic clue for APDS.
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http://dx.doi.org/10.3389/fimmu.2021.670312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113859PMC
April 2021

Systematic Analysis of MYB Genes Family in Acer rubrum and Functional Characterization of ArMYB89 Gene.

J Exp Bot 2021 May 16. Epub 2021 May 16.

Institute of Agricultural Engineering, Anhui Academy of Agricultural Sciences, Hefei, China.

The MYB transcription factor (TF) family is extensively distributed across the plant kingdom. However, the functional significance of red maple MYB TFs remains unclear. Our research identified 393 MYB transcription factors in the Acer rubrum genome, and these ArMYB members were unevenly distributed across 34 chromosomes. Among them, R2R3 was the primary MYB subclass, which was further divided into 21 subgroups with their Arabidopsis homologs. The evolution of the ArMYB family was also investigated, with the results revealing several R2R3-MYB subgroups with expanded membership in woody species. Quantitative real-time PCR analysis revealed that the ArMYB89 transcription level was significantly up-regulated in red leaves in contrast to green leaves. Here, we report on the isolation and characterization of ArMYB89 in red maple. Subcellular localization experiments indicated that ArMYB89 was localized on the nucleus. Further experiments revealed that ArMYB89 could interact with ArSGT1 in vitro and in vivo. The overexpression of ArMYB89 in tobacco might enhance the anthocyanin content of transgenic plants. In conclusion, our results contributed to the elucidation of a theoretical basis for the ArMYB gene family and provides a foundation for the further characterization of the biological roles of MYB genes in the regulation of Acer rubrum leaf color.
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http://dx.doi.org/10.1093/jxb/erab213DOI Listing
May 2021

Cephalomannine inhibits hypoxia-induced cellular function via the suppression of APEX1/HIF-1α interaction in lung cancer.

Cell Death Dis 2021 May 14;12(5):490. Epub 2021 May 14.

School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R. China.

Lung cancer (LC) is one of the leading causes of cancer-related death. As one of the key features of tumor microenvironment, hypoxia conditions are associated with poor prognosis in LC patients. Upregulation of hypoxic-induced factor-1α (HIF-1α) leads to the activation of various factors that contribute to the increased drug resistance, proliferation, and migration of tumor cells. Apurinic/apyrimidinic endonuclease-1 (APEX1) is a multi-functional protein that regulates several transcription factors, including HIF-1α, that contribute to tumor growth, oxidative stress responses, and DNA damage. In this study, we explored the mechanisms underlying cell responses to hypoxia and modulation of APEX1, which regulate HIF-1α and downstream pathways. We found that hypoxia-induced APEX1/HIF-1α pathways regulate several key cellular functions, including reactive oxygen species (ROS) production, carbonic anhydrase 9 (CA9)-mediated intracellular pH, migration, and angiogenesis. Cephalomannine (CPM), a natural compound, exerted inhibitory effects in hypoxic LC cells via the inhibition of APEX1/HIF-1α interaction in vitro and in vivo. CPM can significantly inhibit cell viability, ROS production, intracellular pH, and migration in hypoxic LC cells as well as angiogenesis of HUVECs under hypoxia through the inhibition of APEX1/HIF-1α interaction. Taken together, CPM could be considered as a promising compound for LC treatment.
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http://dx.doi.org/10.1038/s41419-021-03771-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121842PMC
May 2021

Impact of the COVID-19 pandemic on asthma control among children: a qualitative study from caregivers' perspectives and experiences.

BMJ Open 2021 05 13;11(5):e046525. Epub 2021 May 13.

School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, China

Objectives: To understand the impact of the COVID-19 epidemic on asthma control in children based on caregivers' perspectives and experiences.

Design: This was a qualitative study deploying face-to-face, semistructured interviews. Thematic analysis was carried out to analyse the data.

Setting: Paediatric respiratory clinics in three tertiary hospitals.

Participants: 16 caregivers providing unpaid asthma-related care and assistance to children under 14 years who had been diagnosed with asthma for more than 1 year and were not only treated with short-acting β2-agonists.

Results: Six main themes were identified: (1) improved asthma control; (2) decreased willingness to seek medical care driven by fear; (3) increased adherence due to enhanced awareness of asthma control; (4) coping strategies for changes caused by COVID-19; (5) a new opportunity and (6) managing new challenges in asthma control.

Conclusions: The COVID-19 outbreak and the measures in response to it have had significant impacts on asthma control among children. Children with asthma are advised to continue good asthma management, take their prescribed asthma medications as normal, wash their hands regularly and wear face masks. Regularly supported self-management and remote consultations should be provided during the COVID-19 pandemic. In addition, supporting people financially, providing continued medical support and alleviating any fear and anxiety should be considered. We anticipate that our findings will inform health promotion interventions.
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http://dx.doi.org/10.1136/bmjopen-2020-046525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126436PMC
May 2021

Achieving realistic gastric emptying curve in an advanced dynamic human digestion system: experiences with cheese-a difficult to empty material.

Food Funct 2021 May;12(9):3965-3977

Department of Chemical Engineering and Biochemical Engineering, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China and School of Chemical and Environmental Engineering, College of Chemistry, Chemical Engineering and Material Science, Soochow University, Suzhou 215123, Jiangsu Province, China.

Nowadays, in vitro digestion models have received growing interest in recent years to track the digestive fate of foods in the gastrointestinal tract. A major challenge in the development of more physiologically relevant in vitro gastric models is to simulate realistic gastric emptying. In this study, an advanced dynamic in vitro human gastric system was investigated for its potential in achieving the above. The mechanisms for controlling the gastric emptying rate by modulations of the peristaltic moving distance, the pylorus opening size/frequency, and the stomach tilting angle in relation to time are illustrated. With solid cheese, a difficult food material for emptying, different combinations of the operational parameters of the stomach system were evaluated. The system was steered to attain consistent gastric emptying curve with the theoretical data by optimizing operational parameters. By fitting the gastric retention data with a power-exponential model, which is a common approach for describing gastric emptying, the total meal achieved an average emptying half-time (t1/2) of 84.5 min and a curve shape coefficient (β) of 1.69, similar to the theoretical data reported in the literature, where the values of t1/2 and β were 85 min and 1.8, respectively (p > 0.05). Furthermore, the mean median particle size was significantly decreased from the initial 2.80 mm (cheese cubes) to the final 1.35 mm (p < 0.05). There are few particles greater than 2 mm observed in the emptied cheese digesta throughout the digestion process. These suggest the powerful gastric grinding and sieving capacity exhibited by the in vitro system. The current study demonstrates that a well-considered in vitro system can offer a reasonable approach for tracking the structural and physicochemical changes of foods during digestion in the stomach, which is practically meaningful.
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http://dx.doi.org/10.1039/d0fo03364bDOI Listing
May 2021

Tolerability, Safety, Pharmacokinetics, and Immunogenicity of a Novel SARS-CoV-2 Neutralizing Antibody, Etesevimab in Chinese Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled, First-In-Human Phase 1 Study.

Antimicrob Agents Chemother 2021 May 10. Epub 2021 May 10.

Phase 1 Clinical Research Center, Huashan Hospital, Fudan University, Shanghai, China

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to spread rapidly worldwide. This study is the first to report the tolerability, safety, pharmacokinetics (PK), and immunogenicity of a recombinant human anti-SARS-CoV-2 monoclonal antibody, etesevimab (CB6, JS016, LY3832479 or LY-CoV016), in healthy adults. This paper involves a randomized, double-blind, placebo-controlled, phase 1 study. A total of 40 participants were enrolled to receive a single intravenous dose of either etesevimab or a placebo in one of four sequential ascending intravenous dose cohorts. All 40 participants completed the study. Seventeen (42.5%) participants experienced 22 treatment emergent adverse events (TEAEs) that were drug-related, and the rates of these TEAEs among different dose cohorts were numerically comparable. No difference was observed between the combined etesevimab group and the placebo group. The exposure after etesevimab infusion increased in an approximately proportional manner as the dose elimination half-life cohorts and was estimated to be around 4 weeks. Etesevimab was well tolerated after administration of a single dose at a range of 2.5 mg/kg to 50 mg/kg in healthy Chinese adults. The PK profiles of etesevimab in healthy volunteers showed typical monoclonal antibody distribution and elimination characteristics. (This study has been registered at ClinicalTrials.gov under identifier NCT04441918.).
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http://dx.doi.org/10.1128/AAC.00350-21DOI Listing
May 2021

Use of Transcriptomic Analyses to Elucidate the Mechanism Governing Nodal Root Development in (Munro) Hack.

Front Plant Sci 2021 23;12:659830. Epub 2021 Apr 23.

The National Forestry and Grassland Administration Engineering Research Center for Germplasm Innovation and Utilization of Warm-season Turfgrasses, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing, China.

Centipedegrass [ (Munro) Hack.] is a perennial warm-season grass that originated in China, and its speed of nodal rooting is important for lawn establishment. In our study, centipedegrass nodal rooting ability was limited by node aging. Transcriptome sequencing of nodal roots after 0, 2, 4, and 8 days of water culture was performed to investigate the molecular mechanisms of root development. GO enrichment and KEGG pathway analyses of DEGs indicated that plant hormone signal transduction and transcription factors might play important roles in centipedegrass nodal root growth. Among them, E3 ubiquitin-protein ligases participated in multiple hormone signal transduction pathways and interacted with transcription factors. Furthermore, an E3 ubiquitin protein ligase overexpressed in rice resulted in longer roots and more numerous root tips, while knockout of (the homologous gene of in rice) resulted in shorter roots and fewer root tips. These results indicated that and its homologous gene are able to promote nodal root development. This research presents the transcriptomic analyses of centipedegrass nodal roots, and may contribute to elucidating the mechanism governing the development of nodal roots and facilitates the use of molecular breeding in improving rooting ability.
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http://dx.doi.org/10.3389/fpls.2021.659830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102984PMC
April 2021

Tai Chi exercise improves age-associated decline in cerebrovascular function: a cross-sectional study.

BMC Geriatr 2021 05 6;21(1):293. Epub 2021 May 6.

School of Physical Education, Wuhan Sports University, 430079, Wuhan, China.

Background: Tai Chi exercise has been reported to enhance physical and mental health in the older adults; however, the mechanism remains elusive.

Trial Design: We recruited 289 older adults practicing Tai Chi for over 3 years, together with 277 age-matched older and 102 young adults as controls. 168 Tai Chi practitioners were successfully matched to 168 older controls aged 60-69 based on a propensity score for statistics.

Methods: Cerebrovascular function was evaluated by measuring the hemodynamics of the carotid artery. Spearman correlation was performed to validate the age-associated physiological parameters.

Results: Cerebrovascular function in older adults significantly degenerated compared with the young, and was substantially correlated with age. Compared with the older control group, Tai Chi practitioners showed significant improvements in CVHI (cerebral vascular hemodynamics indices) Score (P = 0.002), mean blood flow velocity (P = 0.014), maximal blood flow velocity (P = 0.04) and minimum blood flow velocity (P < 0.001), whereas the age-related increases in pulse wave velocity (P = 0.022), characteristic impedance (P = 0.021) and peripheral resistance (P = 0.044) were lowered.

Conclusions: These data demonstrate a rejuvenation role of Tai Chi in improving the age-related decline of the cerebrovascular function.

Trial Registration: Chinese Clinical Trial Registry (ChiCTR1900025187).
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http://dx.doi.org/10.1186/s12877-021-02196-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101197PMC
May 2021