Publications by authors named "Lingling Zhang"

569 Publications

Clinicians' Perspectives About the Feasibility and Effectiveness of Using Telemedicine in First Aid: A Qualitative Study.

Int J Gen Med 2021 12;14:3343-3353. Epub 2021 Jul 12.

School of Nursing, Nanchang University, Nanchang, 330006, People's Republic of China.

Objective: This study investigated clinicians' perspectives on the feasibility and effectiveness of using telemedicine in the context of providing first aid. It is crucial to identify and explore clinicians' attitudes and awareness of tele-first-aid in China to keep pace with ongoing global trends.

Design: This was a qualitative study. Data gathered from in-depth interviews with 22 clinicians were coded into themes and analyzed.

Participants: Participants included hospital-based clinicians: four clinical specialists, eight emergency nurses, four emergency doctors, three general practitioners, and three clinical administrators.

Setting: The study was conducted in university-affiliated hospitals.

Results: All clinicians who were invited to participate believed that the use of telemedicine in first aid was promising and effective. Participants stated that relevant technology should be designed to synergize the chain of existing platforms in the industry and that it should be determined who has the authority to utilize such technology and how it should be used to achieve the sought-after benefits. The use of such technology refreshes the role of clinicians and their relationship with patients. Additionally, participants believed that the government could play an important role especially in the reform of medical systems.

Conclusion: Telemedicine can facilitate the provision of conventional first aid and systematically exploit existing resources due to its feasibility and effectiveness. The social benefits of using tele-first-aid in clinical and community applications, especially when used in coordination with existing resources, make its adoption an inevitable trend in the field.
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http://dx.doi.org/10.2147/IJGM.S314901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285227PMC
July 2021

SENP3-Mediated PPARγ2 DeSUMOylation in BM-MSCs Potentiates Glucocorticoid-Induced Osteoporosis by Promoting Adipogenesis and Weakening Osteogenesis.

Front Cell Dev Biol 2021 24;9:693079. Epub 2021 Jun 24.

Musculoskeletal Tumor Center, Department of Orthopedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.

Glucocorticoid-induced osteoporosis (GIOP) is the most common secondary osteoporosis and reduced bone formation was the main pathological change in GIOP. Our previous studies have shown that there was an imbalance between adipogenic and osteogenic differentiation in GIOP BM-MSCs and peroxisome proliferator-activated receptor γ2 (PPARγ2) played a vital role in this disorders. Here, we reported that there was an increase in ROS level and SENP3 expression in Dex-induced osteoporotic BM-MSCs, and enhanced adipogenesis and weakened osteogenesis in osteoporotic BM-MSCs might be caused by upregulated SENP3. Then we found that SENP3 de-SUMOylated PPARγ2 on K107 site to potentiate adipogenesis and weaken osteogenesis. These results may provide new strategy and target in the clinical diagnosis and treatment of GIOP.
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http://dx.doi.org/10.3389/fcell.2021.693079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266396PMC
June 2021

Identification and functional characterization of RsGST1, an anthocyanin-related glutathione S-transferase gene in radish.

J Plant Physiol 2021 Aug 2;263:153468. Epub 2021 Jul 2.

School of Advanced Agriculture and Bioengineering, Yangtze Normal University, Chongqing, 408100, PR China; College of Horticulture, South China Agricultural University, Guangzhou, 510642, PR China. Electronic address:

Anthocyanins not only affect the quality of horticultural crops but are also vital for human health. Glutathione transferase family members (GSTs) are enzymes that help to control plant development and stress responses, and are also involved in anthocyanin accumulation. In this study, we targeted a phi (F) class glutathione S-transferase gene RsGST1 (RSG01330.t1) as a crucial gene in the accumulation of anthocyanins in radish. RsGST1 expression was closely associated with anthocyanin content in the skin and flesh of taproot from different color type radish cultivars. Furthermore, RsGST1 was able to restore anthocyanin accumulation in Arabidopsis tt19 mutants, indicating that RsGST1 has a similar function as AtTT19, a gene responsible for the transport of anthocyanins in Arabidopsis. Transient overexpression of RsGST1 together with the key anthocyanin biosynthesis regulator RsMYB1a in radish leaves significantly enhanced anthocyanin biosynthesis compared with in plants that overexpressed RsMYB1a alone. Dual-luciferase and yeast one-hybrid assays revealed that RsMYB1a binds to promotor and activates the expression of RsGST1. Altogether, these results provide molecular evidence indicating that RsGST1 and RsMYB1a coordinate radish anthocyanin accumulation.
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http://dx.doi.org/10.1016/j.jplph.2021.153468DOI Listing
August 2021

Absorption, metabolism, excretion, and safety of [C]almonertinib in healthy Chinese subjects.

Ann Transl Med 2021 May;9(10):867

Phase I Clinical Trial Unit, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Background: Almonertinib Mesilate Tablets (HS-10296, Hansoh Pharma, Shanghai, China) is a novel and selective third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). A phase I study of almonertinib in patients with non-small cell lung cancer (NSCLC) demonstrated a linear metabolic trend, a good tolerability/safety profile, and preliminary antitumor activity. However, the metabolism, excretion, and substance balance of almonertinib has not been clearly determined. Here, we investigated the pharmacokinetic characteristics and safety profile of almonertinib following a single oral dose (110 mg/50 µCi) in healthy Chinese male participants.

Methods: Total radioactivity (TRA) in whole blood, plasma, urine, and feces was measured by utilizing a liquid scintillation counter to obtain almonertinib substance balance data. The pharmacokinetic parameters of [C]almonertinib and the parent drug almonertinib in whole blood and plasma were analyzed with noncompartmental analysis in the WinNonlin software (Pharsight Corp). The major metabolites in plasma, urine, and feces were analyzed by high-performance liquid chromatography (HPLC) coupled with an online or offline isotope detector. The safety of the drug was evaluated after administration.

Results: The safety and tolerability of a single oral dose of 110 mg/50 µCi [C] almonertinib suspension were good in healthy Chinese male participants. There was no significant abnormality or special adverse reaction. TRA peaked quickly in plasma, with a T of 4.0 h; however, TRA was cleared slowly , with a mean terminal elimination phase (half-life, T) of up to 863 h. In addition to the parent drug, a total of 26 metabolites in blood, urine, and feces were analyzed. In plasma, parent drug was the major drug-related component, accounting for 69.97% of TRA, and M440 (almonertinib-M2 demethyl product) was the major metabolite, accounting for 5.08% of TRA; in urine, parent drug accounted for 0.48% of the dose administered and HAS-719 was the major metabolite, accounting for 1.20% of the administered dose; in feces, parent drug was about 8.61% of the dose administered and HAS-719 was the major metabolite, accounting for 12.33% of the administered dose, which was followed by M541a/M470a and M617/M575, accounting for 11.8% and 6.76% of the administered dose, respectively.

Conclusions: Almonertinib has a good safety profile, with parent drug as its main circulating component. almonertinib is extensively metabolized before excretion and is excreted as a parent drug and metabolites mainly via feces.

Trial Registration: The trial registration number: CTR20192291.
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http://dx.doi.org/10.21037/atm-21-1606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184462PMC
May 2021

Antifungal mechanisms of lavender essential oil in the inhibition of rot disease caused by Monilinia fructicola in postharvest flat peaches.

Can J Microbiol 2021 Jun 21. Epub 2021 Jun 21.

Shaanxi Normal University, 12401, Xi'an, Shaanxi, China;

As a natural antimicrobial agent, lavender essential oil (LEO) is generally recognized to be safe and effective in the inhibition of phytopathogenic fungi. Direct contact and fumigation (in vivo and in vitro) were used to study the fungistatic effect of LEO on Monilinia fructicola. Additionally, the effect on the ultrastructure of cells and degree of destruction of the cell membrane of M. fructicola were revealed. In addition, the effects of LEO on the expression levels of particular apoptosis-related genes in M. fructicola cells were detected and GC-MS was used to analyse the main components of LEO. LEO had a good inhibitory efficacy against M. fructicola in flat peaches, with almost complete growth inhibition with 800 μL / L. These effects were associated with leakage of cytoplasm contents, hyphal distortion and spore disruption. Moreover, the expression of apoptosis RTG1 and RLM1 genes increased on LEO treatment. These results demonstrate that LEO can inhibit M. fructicola by inducing cytoplasmic membrane damage and cell apoptosis of fungi and that the major ingredients of LEO are monoterpenes and sesquiterpenes which are presumed to contribute to the inhibitory effects.
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http://dx.doi.org/10.1139/cjm-2020-0484DOI Listing
June 2021

Dual-Wavelength Photosensitive Nano-in-Micro Scaffold Regulates Innate and Adaptive Immune Responses for Osteogenesis.

Nanomicro Lett 2020 Nov 21;13(1):28. Epub 2020 Nov 21.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine, Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, 430079, People's Republic of China.

The immune response of a biomaterial determines its osteoinductive effect. Although the mechanisms by which some immune cells promote regeneration have been revealed, the biomaterial-induced immune response is a dynamic process involving multiple cells. Currently, it is challenging to accurately regulate the innate and adaptive immune responses to promote osteoinduction in biomaterials. Herein, we investigated the roles of macrophages and dendritic cells (DCs) during the osteoinduction of biphasic calcium phosphate (BCP) scaffolds. We found that osteoinductive BCP directed M2 macrophage polarization and inhibited DC maturation, resulting in low T cell response and efficient osteogenesis. Accordingly, a dual-targeting nano-in-micro scaffold (BCP loaded with gold nanocage, BCP-GNC) was designed to regulate the immune responses of macrophages and DCs. Through a dual-wavelength photosensitive switch, BCP-GNC releases interleukin-4 in the early stage of osteoinduction to target M2 macrophages and then releases dexamethasone in the later stage to target immature DCs, creating a desirable inflammatory environment for osteogenesis. This study demonstrates that biomaterials developed to have specific regulatory capacities for immune cells can be used to control the early inflammatory responses of implanted materials and induce osteogenesis.
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http://dx.doi.org/10.1007/s40820-020-00540-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187671PMC
November 2020

Leisure time physical activity and risk of pneumonia mortality: a dose-response meta-analysis.

J Sports Med Phys Fitness 2021 Jun 16. Epub 2021 Jun 16.

School of Physical Education and Sports, Central China Normal University, Wuhan, China.

Introduction: This meta-analysis of cohort studies aimed to examine the doseresponse relationships between LPTA (Leisure time physical activity) and pneumonia mortality to provide some suggestions for the prevention of respiratory disease mortality.

Evidence Acquisition: PubMed、WOS database was systematically searched for eligible studies until Nov.1, 2020. The prospective cohort study on the relationship between LPTA and pneumonia mortality was collected. The Meta-analysis was performed using Stata 14 software to calculate the combined effect size (HR) of pneumonia mortality and its 95% CI in a categorical dose-response relationship. The restrictive cubic spline model was used to fit the continuous dose-response relationship.

Evidence Synthesis: Eight cohort studies included 370045 subjects who met the inclusion criteria. The categorical dose-relational analysis revealed that the highest dose compared to the lowest LTPA dose reduced the risk of pneumonia mortality by 32%(HR=0.68.95% CI:0.64-0.73). The continuous dose-response relationship results showed a negative nonlinear relationship between LTPA and the risk of pneumonia mortality (PNon-linearity<0.05). The risk of pneumonia death HR decreased by 16%(p<0.01, HR=0.84.95%CI:0.82-0.86) for each additional 5 MET-h/week when LTPA below 20 MET-h/week. When LTPA was higher than 20 MET-h/week, the risk of pneumonia death HR decreased by 6% for each additional 5 MET-h/week(p<0.01, HR=0.94,95%CI:0.93-0.94).

Conclusions: All doses of LTPA are protective factors of pneumonia mortality risk and the protective effect on pneumonia mortality is enhanced if LTPA increases. The degree of enhancement is weakened when LTPA is higher than 20 MET-h/week.
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http://dx.doi.org/10.23736/S0022-4707.21.12017-1DOI Listing
June 2021

A 4-aminonaphthalimide-based fluorescent traceable prodrug with excellent photoinduced cytotoxicity.

Chem Commun (Camb) 2021 Jul;57(53):6558-6561

Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China. and University of Chinese Academy of Sciences, Beijing, 100049, China and School of Molecular Medicine, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310013, China.

A blue light activated anti-cancer prodrug, NST, was designed based on a photoactive 4-aminonaphthalimide derivative and an anticancer drug, 10-hydroxycamptothecin. NST was hard to be taken up by living cells and showed negligible dark cytotoxicity. The irradiation caused photocleavage of NST and resulted in high cytotoxicity.
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http://dx.doi.org/10.1039/d1cc01847gDOI Listing
July 2021

A Norrin/Wnt surrogate antibody stimulates endothelial cell barrier function and rescues retinopathy.

EMBO Mol Med 2021 Jul 9;13(7):e13977. Epub 2021 Jun 9.

Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.

The FZD4:LRP5:TSPAN12 receptor complex is activated by the secreted protein Norrin in retinal endothelial cells and leads to βcatenin-dependent formation of the blood-retina-barrier during development and its homeostasis in adults. Mutations disrupting Norrin signaling have been identified in several congenital diseases leading to hypovascularization of the retina and blindness. Here, we developed F4L5.13, a tetravalent antibody designed to induce FZD4 and LRP5 proximity in such a way as to trigger βcatenin signaling. Treatment of cultured endothelial cells with F4L5.13 rescued permeability induced by VEGF in part by promoting surface expression of junction proteins. Treatment of Tspan12 mice with F4L5.13 restored retinal angiogenesis and barrier function. F4L5.13 treatment also significantly normalized neovascularization in an oxygen-induced retinopathy model revealing a novel therapeutic strategy for diseases characterized by abnormal angiogenesis and/or barrier dysfunction.
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http://dx.doi.org/10.15252/emmm.202113977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261507PMC
July 2021

New type of borneol-based fluorine-free superhydrophobic antibacterial polymeric coating.

Des Monomers Polym 2021 May 7;24(1):145-155. Epub 2021 May 7.

Key Laboratory of Science and Technology of EcoTextile, Donghua University, Ministry of Education, Shanghai, China.

A new type of superhydrophobic borneol-based polymeric coating has been prepared. The chemical composition of the polymer particles was analyzed by Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy, which showed that the polymer did not contain fluorine, which can effectively avoid the cytotoxic risk of fluorine. By dynamic light scattering, scanning electron microscopy, and static contact angle measurement, the contact angle of the prepared coating gradually increased with increasing diameter of the polymer particles, and a superhydrophobic coating surface was finally obtained. Interestingly, after dissolving the superhydrophobic sample with tetrahydrofuran and making it a normal hydrophobic sample, the antiadhesion performance for was greatly reduced, and it could not effectively prevent adhesion. In addition, a long-term antiadhesion study of bacteria was performed. The superhydrophobic borneol-based polymer coating showed long-term resistance to adhesion. Therefore, the excellent antibacterial properties and cell compatibility mean that this series of polymer materials has great potential in the field of biomedicine.
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http://dx.doi.org/10.1080/15685551.2021.1924959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118525PMC
May 2021

Role of C-X-C motif chemokine ligand 14 promoter region DNA methylation and single nucleotide polymorphism in influenza A severity.

Respir Med 2021 May 18;185:106462. Epub 2021 May 18.

Clinical Laboratory, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province 610072, China. Electronic address:

Objective: The purpose of our experiment is to discuss the function of DNA methylation and single nucleotide polymorphism (SNP) in C-X-C motif chemokine ligand 14 (CXCL14) promoter region in influenza A (H1N1) severity.

Methods: Clinic data and blood samples from H1N1 patients were collected. Blood routine indexes were measured. Levels of T lymphocytes were assessed. Importantly, CXCL14 expression and methylation in H1N1 patients and A549 cells were detected through functional assays. Additionally, rs2237061, rs2237062 and rs2547 of CXCL14 were genotyped to analyze the relation of CXCL14 SNP and H1N1 severity.

Results: The number of leukocytes, neutrophils and lymphocytes as well as T lymphocytes in H1N1 patients was lower than that in healthy subjects, and that was decreased in severe H1N1 patients compared with the mild H1N1 patients. In HIN1 patients, CXCL14 expression was decreased, while CXCL14 methylation was increased, and CXCL14 expression was further decreased and CXCL14 methylation was further increased in severe H1N1 patients. CXCL14 methylation was negatively correlated with T lymphocytes in H1N1 patients. CXCL14 methylation was elevated in H1N1-infected A549 cells. GA and AA genotypes of rs2547 in CXCL14 were risky genotypes for H1N1, and AA genotype was risky genotype for severe H1N1. Number of T lymphocytes was lower in H1N1 patients carrying AA genotype of rs2547 than that in GA + GG genotype.

Conclusion: CXCL14 promoter region DNA methylation and SNP were correlated with H1N1 severity.
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http://dx.doi.org/10.1016/j.rmed.2021.106462DOI Listing
May 2021

Thoracoscopic radical resection in the treatment of NSCLC patients (stage IIIA) after neoadjuvant chemotherapy.

J BUON 2021 Mar-Apr;26(2):313-319

Department of Oncology, Binzhou People's Hospital, Binzhou 256610, China.

Purpose: We aimed to investigate the efficacy and safety of thoracoscopic radical resection of lung cancer in the treatment of patients with stage IIIA non-small cell lung cancer (NSCLC) after neoadjuvant chemotherapy.

Methods: A total of 132 NSCLC patients (stage IIIA) were collected. Among them, 66 received preoperative neoadjuvant chemotherapy and thoracoscopic radical resection of lung cancer (NACT group), and 66 underwent thoracoscopic radical resection of lung cancer directly (control group). Next, the downstaging of the tumor was analyzed after neoadjuvant chemotherapy, and the R0 resection rate, surgical conditions, postoperative complications, and changes in the levels of serum tumor markers were compared between the two groups of patients.

Results: The response rate of neoadjuvant chemotherapy was 51.5% (34/66), and the overall downstaging rate was 53.0% (35/66) after neoadjuvant chemotherapy, with 34 cases of T downstaging and 35 cases of N downstaging. The operative time was clearly shorter in the NACT group than that in control group. The R0 resection rate in the NACT group was prominently higher than that in the the control group. The follow-up results uncovered that the 3-year overall survival (OS) and 3-year progression-free survival (PFS) rates were 50.0% and 21.2% in the NACT group, and 36.4% and 6.1% in the control group, respectively. Based on the results of log-rank test, the OS and PFS of patients in the NACT group were markedly better than those in the control group.

Conclusions: Neoadjuvant chemotherapy benefits patients with NSCLC (stage IIIA), and it is capable of effectively leading to pathological down-staging, elevating the R0 resection rate, significantly improving the survival of patients and considerably repressing the progression of the disease.
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June 2021

Toward Hand Pattern Recognition in Assistive and Rehabilitation Robotics Using EMG and Kinematics.

Front Neurorobot 2021 13;15:659876. Epub 2021 May 13.

Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, China.

Wearable hand robots are becoming an attractive means in the facilitating of assistance with daily living and hand rehabilitation exercises for patients after stroke. Pattern recognition is a crucial step toward the development of wearable hand robots. Electromyography (EMG) is a commonly used biological signal for hand pattern recognition. However, the EMG based pattern recognition performance in assistive and rehabilitation robotics post stroke remains unsatisfactory. Moreover, low cost kinematic sensors such as Leap Motion is recently used for pattern recognition in various applications. This study proposes feature fusion and decision fusion method that combines EMG features and kinematic features for hand pattern recognition toward application in upper limb assistive and rehabilitation robotics. Ten normal subjects and five post stroke patients participating in the experiments were tested with eight hand patterns of daily activities while EMG and kinematics were recorded simultaneously. Results showed that average hand pattern recognition accuracy for post stroke patients was 83% for EMG features only, 84.71% for kinematic features only, 96.43% for feature fusion of EMG and kinematics, 91.18% for decision fusion of EMG and kinematics. The feature fusion and decision fusion was robust as three different levels of noise was given to the classifiers resulting in small decrease of classification accuracy. Different channel combination comparisons showed the fusion classifiers would be robust despite failure of specific EMG channels which means that the system has promising potential in the field of assistive and rehabilitation robotics. Future work will be conducted with real-time pattern classification on stroke survivors.
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http://dx.doi.org/10.3389/fnbot.2021.659876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155590PMC
May 2021

Topical epigallocatechin-3-gallate in the treatment of vitiligo.

Australas J Dermatol 2021 May 28. Epub 2021 May 28.

Department of Dermatology, Third People's Hospital of Hangzhou, Hangzhou, China.

Objective: To preliminarily assess the efficacy and safety of the topical application of Epigallocatechin-3-gallate (EGCG) in treating vitiligo, a 6-month clinical trial was carried out.

Method: Patients were randomly given topical application of EGCG on the assigned lesions, with pimecrolimus being used as the control for twice a day over a 6-month treatment period. Responses to treatment were assessed based on the changes in VASI score for percentage reduction in body surface area and the PGA scores.

Results: According to our results, both drugs were discovered to be markedly effective on repigmentation. The VASI of lesion had diminished from 1.19 ± 0.42 to 0.63 ± 0.38, in the EGCG-treated lesions, while from 1.18 ± 0.43 to 0.61 ± 0.36 in the pimecrolimus-treated lesions, and there was no statistically significant difference in VASI score between the EGCG-treated lesions and pimecrolimus-treated lesions (P = 0.755). Meanwhile, the mean PGA score on the EGCG applied side was 4.39 ± 2.23, while that was 4.43 ± 2.02 on the pimecrolimus applied side (P = 0.886). Furthermore, difference in the improvement degree between pimecrolimus side and EGCG side was not statistically significant (P = 0.845). Notably, no serious side effects were observed throughout the study.

Conclusion: Findings of the study indicate that topical EGCG can be effective on treating vitiligo.
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http://dx.doi.org/10.1111/ajd.13612DOI Listing
May 2021

Application of a crisis management nursing system in the novel coronavirus pneumonia epidemic.

Am J Transl Res 2021 15;13(4):3689-3695. Epub 2021 Apr 15.

Director of The Hospital, The Third Affiliated Hospital of Qiqihar Medical University Qiqihar, Heilongjiang Province, China.

Objective: To explore the application of a nursing crisis management system in the novel coronavirus pneumonia epidemic.

Methods: A retrospective nursing method was implemented. A total of 280 cases of patients were diagnosed with coronavirus pneumonia in the isolation ward of our hospital. The 280 cases of newly diagnosed pneumonia were divided into two groups: the nursing crisis management system group (n=150, the nursing crisis management was given) and the non-nursing crisis management system (n=130, routine nursing management was given). The psychological status (profile of mood states (POMS) score) of nursing staff before and after the implementation of the nursing crisis management, the psychological status of patients after the implementation of nursing crisis management (POMS score), emotion, cognition, behavior severity, patients' satisfaction with nursing, treatment compliance (Morisky Medication Compliance Scale (MMAS) score) of patients, the rate of cure of patients and the infection rate of nursing staff were compared.

Results: Compared with the non-nursing crisis management system group, the POMS scores of patients and nurses in the nursing crisis management system group decreased (all P<0.05). Compared with the non-nursing crisis management system group, the emotional, cognitive and behavioral scores of patients in the nursing crisis management system group were lower, while the MMAS score, satisfaction with nursing and cure rate were significantly increased (all P<0.05). The 142 nursing staff did not catch coronavirus.

Conclusion: During the novel coronavirus pneumonia outbreak and the current normal epidemic prevention and control periods, our crisis management mode was introduced into nursing work. The construction of the nursing crisis management mode under the epidemic situation can improve the psychological state and improve the management efficiency of the patients and nurses. The patients' satisfaction is high and the treatment compliance is good.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129237PMC
April 2021

EHD3 positively regulated by NR5A1 participates in testosterone synthesis via endocytosis.

Life Sci 2021 Aug 5;278:119570. Epub 2021 May 5.

NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), School of Pharmacy, Fudan University, Shanghai 200032, China; NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, Shanghai 200032, China. Electronic address:

Aims: Increasing evidence has shown that hormone secretion is regulated by endocytosis. Eps15 homology domain-containing protein 3 (EHD3) is an endocytic-trafficking regulatory protein, but whether EHD3 is associated with testosterone secretion is not clear. This work aims to explore the role of EHD3 in testosterone synthesis.

Main Methods: Testosterone concentration was determined by ELISA. The effects of EHD3 on endocytosis were assessed by exosomes tracing assay and Immunofluorescence. Targeting relationship between EHD3 and NR5A1 was verified by chromatin immunoprecipitation (ChIP) and dual luciferase reporter gene assay in Leydig cells. For in vivo assessments, conditional NR5A1 knockout mouse model was established with CRISPR/Cas9 gene targeting technology.

Key Findings: EHD3 overexpression significantly increased the concentration of testosterone. EHD3 knockdown markedly decreased testosterone synthesis by reducing endocytosis. The activity of the EHD3 promoter was positively regulated by NR5A1, which occupied the conserved sequence "AGGTCA" in the EHD3 promoter. Furthermore, mice with a Leydig cell-specific conditional NR5A1 knockout displayed the blunted levels of EHD3 and clathrin (a key factor for endocytosis), and serum testosterone concentration compared with NR5A1 mice.

Significance: This study suggests a potential molecular mechanism of testosterone synthesis to fully understand male reproductive health.
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http://dx.doi.org/10.1016/j.lfs.2021.119570DOI Listing
August 2021

Richer fusion network for breast cancer classification based on multimodal data.

BMC Med Inform Decis Mak 2021 04 22;21(Suppl 1):134. Epub 2021 Apr 22.

Department of Oncology, Peking University International Hospital, Beijing, China.

Background: Deep learning algorithms significantly improve the accuracy of pathological image classification, but the accuracy of breast cancer classification using only single-mode pathological images still cannot meet the needs of clinical practice. Inspired by the real scenario of pathologists reading pathological images for diagnosis, we integrate pathological images and structured data extracted from clinical electronic medical record (EMR) to further improve the accuracy of breast cancer classification.

Methods: In this paper, we propose a new richer fusion network for the classification of benign and malignant breast cancer based on multimodal data. To make pathological image can be integrated more sufficient with structured EMR data, we proposed a method to extract richer multilevel feature representation of the pathological image from multiple convolutional layers. Meanwhile, to minimize the information loss for each modality before data fusion, we use the denoising autoencoder as a way to increase the low-dimensional structured EMR data to high-dimensional, instead of reducing the high-dimensional image data to low-dimensional before data fusion. In addition, denoising autoencoder naturally generalizes our method to make the accurate prediction with partially missing structured EMR data.

Results: The experimental results show that the proposed method is superior to the most advanced method in terms of the average classification accuracy (92.9%). In addition, we have released a dataset containing structured data from 185 patients that were extracted from EMR and 3764 paired pathological images of breast cancer, which can be publicly downloaded from http://ear.ict.ac.cn/?page_id=1663 .

Conclusions: We utilized a new richer fusion network to integrate highly heterogeneous data to leverage the structured EMR data to improve the accuracy of pathological image classification. Therefore, the application of automatic breast cancer classification algorithms in clinical practice becomes possible. Due to the generality of the proposed fusion method, it can be straightforwardly extended to the fusion of other structured data and unstructured data.
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http://dx.doi.org/10.1186/s12911-020-01340-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061018PMC
April 2021

FOXP3‑induced LINC00885 promotes the proliferation and invasion of cervical cancer cells.

Mol Med Rep 2021 06 21;23(6). Epub 2021 Apr 21.

Department of Gynecological Oncology, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, P.R. China.

Cervical cancer (CC) is the fourth most common type of cancer in women worldwide. LINC00885, a novel oncogenic type of long non‑coding RNA, is upregulated in various types of cancer, but its expression in CC remains unknown. The aim of the present study was to investigate the expression of LINC00885 in CC, and its effect on the proliferation and invasion of CC cells . The expression levels of LINC00885 and forkhead box protein 3 (FOXP3) from The Cancer Genome Atlas (TCGA) were selected to analyze the differences between CC tissues and normal cervical tissues using bioinformatics analyses. Reverse transcription‑quantitative (RT‑q)PCR was used to detect the relative expression of LINC00885 in CC cell lines, and its expression was knocked down. Cell Counting Kit‑8 assays and EdU staining were used to detect the changes in cell proliferative capacity of cells. Transwell experiments were used to examine cell invasion. Dual‑luciferase reporter and chromatin immunoprecipitation assays were performed to examine the interactions between LINC00885 and FOXP3. FOXP3 and epithelial‑mesenchymal transition (EMT)‑related proteins were detected using western blotting. The expression of LINC00885 and FOXP3 in CC tissues and CC cells was significantly higher compared with the normal cervical tissues and normal cervical epithelial cells. FOXP3 could specifically interact with the promoter of LINC00885 and activate LINC00885 transcription. Knockdown of LINC00885 and silencing of FOXP3 significantly inhibited proliferation, invasion and EMT of CC cells. Overexpression of LINC00885 reversed the inhibitory effects of FOXP3 knockdown on the proliferation and invasion of CC cells. Collectively, LINC00885 and FOXP3 may serve as biomarkers for the early diagnosis of CC and as a potential therapeutic target for reversing the malignant phenotype of CC.
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http://dx.doi.org/10.3892/mmr.2021.12097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072316PMC
June 2021

Expression of the Testis-Specific Serine/Threonine Kinases Suggests Their Role in Spermiogenesis of Bay Scallop .

Front Physiol 2021 30;12:657559. Epub 2021 Mar 30.

MOE Key Laboratory of Marine Genetics and Breeding, Ocean University of China, Qingdao, China.

Members of the testis-specific serine/threonine kinases (Tssk) family play critical roles in spermatogenesis in vertebrates. But in mollusks, research on Tssk family is still lagging. In this study, we systematically identified Tssk family based on the genomic and transcriptomic data from a commercially important scallop and detected the spatiotemporal expression in adult gonads. Five members were identified, with the gene length varying from 1,068 to 10,729 bp and the protein length ranging from 294 to 731 aa. All the Tssks possess a serine/threonine protein kinase catalytic (S_TKc) domain. Phylogenetic analysis revealed existence of four homologs of vertebrate Tssk1/2, Tssk3, Tssk4, Tssk5, and absence of Tssk6 in the scallop. The remaining gene (Tssk7) formed an independent clade with Tssks of other mollusks and arthropods, indicating that it may be a new member of Tssk family unique to protostomes. By investigating the expression of in four developmental stages of testes and ovaries, we found all five were primarily expressed in mature testis. hybridization experiment revealed the five were localized in the spermatids and spermatozoa. The testis-predominant expression of Tssk family suggests Tssks may play pivotal roles in spermiogenesis in the scallop. Our study provides basic information on the characteristics and expression profiles of Tssk family of . To our knowledge, it represents the first comprehensive analysis of Tssk family in mollusks.
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http://dx.doi.org/10.3389/fphys.2021.657559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042308PMC
March 2021

The role of the bubble-bubble interaction on radial pulsations of bubbles.

Ultrason Sonochem 2021 May 24;73:105535. Epub 2021 Mar 24.

The Key Laboratory of Modern Acoustics, Ministry of Education, Institution of Acoustics, Nanjing University, Nanjing 210093, China. Electronic address:

Using a model that with or without considering the interaction between bubbles through the radiated pressure waves, numerical simulations of cavitation bubbles have been performed in order to study the effect of the bubble-bubble interaction on radial pulsations of bubbles. Comparing the results obtained by with or without considering the bubble-bubble interaction, it is suggested that the suppression or enlargement property of expansion ratios of bubbles due to the bubble-bubble interaction largely depends on the ultrasound parameters, the ambient bubble radii, the distances between bubbles and the number of bubbles (in multi-bubble environment, the last two aspects can be expressed using the coupling strength). The frequency response curve of expansion ratio decreases and shifts to left due to the bubble-bubble interaction and the larger the coupling strength is, the more the left-shifting is.
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http://dx.doi.org/10.1016/j.ultsonch.2021.105535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050038PMC
May 2021

Knockout of Two Cry-Binding Aminopeptidase N Isoforms Does Not Change Susceptibility of Larvae to subsp. Cry4Ba and Cry11Aa Toxins.

Insects 2021 Mar 5;12(3). Epub 2021 Mar 5.

State Key Laboratory of Ecological Pest Control for Fujian and Taiwan Crops, College of Plant Protection, Fujian Agriculture and Forestry University (FAFU), Fuzhou 350002, China.

The insecticidal Cry4Ba and Cry11Aa crystal proteins from subsp. (Bti) are highly toxic to larvae. The glycosylphosphatidylinositol (GPI)-anchored APN was identified as an important membrane-bound receptor for multiple Cry toxins in numerous Lepidoptera, Coleoptera, and Diptera insects. However, there is no direct molecular evidence to link APN of to Bti toxicity . In this study, two Cry4Ba/Cry11Aa-binding GPI-APN isoforms (APN1 and APN2) were individually knocked-out using CRISPR/Cas9 mutagenesis, and the APN1/APN2 double-mutant homozygous strain was generated using the reverse genetics approach. ELISA assays showed that the high binding affinity of Cry4Ba and Cry11Aa protoxins to the midgut brush border membrane vesicles (BBMVs) from these APN knockouts was similar to the background from the wild-type (WT) strain. Likewise, the bioassay results showed that neither the single knockout of APN1 or APN2, nor the simultaneous disruption of APN1 and APN2 resulted in significant changes in susceptibility of larvae to Cry4Ba and Cry11Aa toxins. Accordingly, our results suggest that APN1 and APN2 may not mediate Bti Cry4Ba and Cry11Aa toxicity in larvae as their binding proteins.
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http://dx.doi.org/10.3390/insects12030223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002144PMC
March 2021

Sexual Development of the Hermaphroditic Scallop Revealed by Morphological, Endocrine and Molecular Analysis.

Front Cell Dev Biol 2021 16;9:646754. Epub 2021 Mar 16.

MOE Key Laboratory of Marine Genetics and Breeding, Ocean University of China, Qingdao, China.

Simultaneous or functional hermaphrodites possessing both ovary and testis at the same time are good materials for studying sexual development. However, previous research on sex determination and differentiation was mainly conducted in gonochoristic species and studies on simultaneous hermaphrodites are still limited. In this study, we conducted a combined morphological, endocrine and molecular study on the gonadal development of a hermaphroditic scallop aged 2-10 month old. Morphological analysis showed that sex differentiation occurred at 6 months of age. By examining the dynamic changes of progesterone, testosterone and estradiol, we found testosterone and estradiol were significantly different between the ovaries and testes almost throughout the whole process, suggesting the two hormones may be involved in scallop sex differentiation. In addition, we identified two critical sex-related genes FoxL2 and Dmrt1L, and investigated their spatiotemporal expression patterns. Results showed that and were female- and male-biased, respectively, and mainly localized in the germ cells and follicular cells, indicating their feasibility as molecular markers for early identification of sex. Further analysis on the changes of and expression in juveniles showed that significant sexual dimorphic expression of occurred at 2 months of age, earlier than that of . Moreover, expression was significantly correlated with estradiol/testosterone ratio (E/T). All these results indicated that molecular sex differentiation occurs earlier than morphological sex differentiation, and may be a key driver that functions through regulating sex steroid hormones in the scallop. This study will deepen our understanding of the molecular mechanism underlying sex differentiation and development in spiralians.
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http://dx.doi.org/10.3389/fcell.2021.646754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007870PMC
March 2021

MicroRNA-124 inhibits hepatic stellate cells inflammatory cytokines secretion by targeting IQGAP1 through NF-κB pathway.

Int Immunopharmacol 2021 Jun 17;95:107520. Epub 2021 Mar 17.

Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Institute of Clinical Pharmacology, Anhui Medical University, Hefei, China. Electronic address:

Liver fibrosis is a health concern that leads to organ failure mediated via production of inflammatory cytokines and fibrotic biomarkers. To date, there was no direct approved antifibrotic therapy, and current treatment was mainly the removal of the causative factor. Recent studies demonstrated that aberrant expression of miR-124 was involved in the progression of various liver diseases including hepatocellular carcinoma (HCC). However, whether miR-124 could function as a transcriptional regulator in the inflammatory cytokines secretion of liver fibrosis remains unclear. In this study, we demonstrated that the expression of miR-124 was downregulated in liver fibrosis tissues and TNF-α-induced LX-2 cells, concomitant with the upregulated expression of IQGAP1, suggesting that miR-124 and IQGAP1 might be associated with the development of inflammation in liver fibrosis. Therefore, we demonstrated that the overexpression of miR-124 and knockdown of IQGAP1 could lead to the downregulation of TNF-α, IL-1β and IL-6. While knockdown of miR-124 or overexpression of IQGAP1 showed reversed results. Moreover, dual luciferase reporter assays demonstrated that miR-124 specifically targeted the 3'-UTR of IQGAP1, and thus inhibited the expression of IQGAP1. Mechanistically, we found that the expression changes of miR-124 and IQGAP1 could be involved in inhibition or activation of NF-κB signaling pathway in response to TNF-α. In conclusion, these results indicated that miR-124 plays a crucial role in TNF-α-induced LX-2 cells via regulating NF-κB signaling pathway.
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http://dx.doi.org/10.1016/j.intimp.2021.107520DOI Listing
June 2021

Neural Fuyuan Formula promotes neural plasticity through BDNF/Trkβ signaling pathway.

Ann Palliat Med 2021 Mar 10;10(3):2926-2934. Epub 2021 Mar 10.

Department of Neurology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Background: Depression after stroke is usually a chronic process, which was associated with many health problems. This study was aimed to investigate the underline mechanism of the effect of Neural Fuyuan Formula (NFF) in post-stroke depression and the role of brain-derived neurotrophic factor (BDNF) in the signal pathway regulated by NFF.

Methods: A rat post-stroke depression model was established. Synaptic plasticity of rat was detected by Electron microscopy. The expression of BDNF signaling proteins and synapse related proteins were measured by Western blot. The expression of Synapsin-1 (SYN1) in rat and the culture neurons was detected by Western blot and immunofluorescence. Dendritic complexity was also measured.

Results: NFF could attenuate the synapse change in the post-stroke depression (PSD) model rat. NFF increased the expression of BDNF signaling proteins and synapse related proteins of the PSD model rat (P&0.05). NFF increased the expression of SYN1 in rat and the culture neurons (P&0.05). NFF could also increase the dendritic complexity in culture neurons (P&0.05).

Conclusions: NFF promoted recovery of neurological function through BDNF signaling pathways, which further affirm the curative effect of NFF for treatment of post-stroke depression.
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http://dx.doi.org/10.21037/apm-19-533DOI Listing
March 2021

Less Unfavorable Salt Bridges on the Enzyme Surface Result in More Organic Cosolvent Resistance.

Angew Chem Int Ed Engl 2021 05 7;60(20):11448-11456. Epub 2021 Apr 7.

Institute of Biotechnology, RWTH Aachen University, Worringer Weg 3, 52074, Aachen, Germany.

Biocatalysis for the synthesis of fine chemicals is highly attractive but usually requires organic (co-)solvents (OSs). However, native enzymes often have low activity and resistance in OSs and at elevated temperatures. Herein, we report a smart salt bridge design strategy for simultaneously improving OS resistance and thermostability of the model enzyme, Bacillus subtilits Lipase A (BSLA). We combined comprehensive experimental studies of 3450 BSLA variants and molecular dynamics simulations of 36 systems. Iterative recombination of four beneficial substitutions yielded superior resistant variants with up to 7.6-fold (D64K/D144K) improved resistance toward three OSs while exhibiting significant thermostability (thermal resistance up to 137-fold, and half-life up to 3.3-fold). Molecular dynamics simulations revealed that locally refined flexibility and strengthened hydration jointly govern the highly increased resistance in OSs and at 50-100 °C. The salt bridge redesign provides protein engineers with a powerful and likely general approach to design OSs- and/or thermal-resistant lipases and other α/β-hydrolases.
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http://dx.doi.org/10.1002/anie.202101642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252522PMC
May 2021

Recent developments on PET radiotracers for TSPO and their applications in neuroimaging.

Acta Pharm Sin B 2021 Feb 25;11(2):373-393. Epub 2020 Aug 25.

Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital & Department of Radiology, Harvard Medical School, Boston, MA 02114, USA.

The 18 kDa translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, is predominately localized to the outer mitochondrial membrane in steroidogenic cells. Brain TSPO expression is relatively low under physiological conditions, but is upregulated in response to glial cell activation. As the primary index of neuroinflammation, TSPO is implicated in the pathogenesis and progression of numerous neuropsychiatric disorders and neurodegenerative diseases, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), multiple sclerosis (MS), major depressive disorder (MDD) and obsessive compulsive disorder (OCD). In this context, numerous TSPO-targeted positron emission tomography (PET) tracers have been developed. Among them, several radioligands have advanced to clinical research studies. In this review, we will overview the recent development of TSPO PET tracers, focusing on the radioligand design, radioisotope labeling, pharmacokinetics, and PET imaging evaluation. Additionally, we will consider current limitations, as well as translational potential for future application of TSPO radiopharmaceuticals. This review aims to not only present the challenges in current TSPO PET imaging, but to also provide a new perspective on TSPO targeted PET tracer discovery efforts. Addressing these challenges will facilitate the translation of TSPO in clinical studies of neuroinflammation associated with central nervous system diseases.
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http://dx.doi.org/10.1016/j.apsb.2020.08.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893127PMC
February 2021

Antifungal Effect of Long Noncoding RNA 9708-1 in the Vulvovaginal Candidiasis Murine Model.

Mycopathologia 2021 May 15;186(2):177-188. Epub 2021 Feb 15.

Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University, Nanjing, 210004, Jiangsu, People's Republic of China.

Vulvovaginal candidiasis (VVC) caused by Candida spp. affects 70-75% of women at least once during their lives. We aim to elucidate the potential mechanism of VVC and investigate the therapeutic effects of long noncoding RNA 9708-1. Female BALB/c mice were randomized to four treatment groups, including the blank control group, VVC control group, vehicle control group and lncRNA 9708-1-overexpressed group. Mice were euthanized on Day 4, Day 7 and Day 14 after treatment. Colony-forming unit (CFU) was measured, and the inflammation was detected by hematoxylin and eosin (H&E). Gene and protein expression levels of lncRNA 9708-1 and FAK were determined by real-time PCR, Western blot and immunohistochemistry. The overexpression of lncRNA 9708-1 significantly decreased the fungal load from Day 4 to 7. H&E staining indicated that the impaired histological profiles were improved in lncRNA 9708-1-overexpressed group. LncRNA 9708-1 led to a significant increase in FAK level of vagina tissue which is expressed mainly in epithelial basal layer. This study suggests that lncRNA 9708-1 played a protective role on murine experimental VVC by upregulating the expression levels of FAK.
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http://dx.doi.org/10.1007/s11046-021-00530-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106589PMC
May 2021

Corrigendum to "Paeonol derivative-6 attenuates inflammation by activating ZEB2 in acute liver injury" [Int. Immunopharmacol. 91 (2021) 107235].

Int Immunopharmacol 2021 May 10;94:107410. Epub 2021 Feb 10.

School of Pharmacy, Anhui Medical University, Hefei 230032, China; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei 230032, China. Electronic address:

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http://dx.doi.org/10.1016/j.intimp.2021.107410DOI Listing
May 2021

Enhanced BCR signaling inflicts early plasmablast and germinal center B cell death.

iScience 2021 Feb 7;24(2):102038. Epub 2021 Jan 7.

Institute of Immunology and Immunotherapy, College of Medical & Dental Sciences/IBR, University of Birmingham, Birmingham, B15 2TT, UK.

It is still not clear how B cell receptor (BCR) signaling intensity affects plasma cell (PC) and germinal center (GC) B cell differentiation. We generated Cγ1 Ptpn6 mice where SHP-1, a negative regulator of BCR signaling, is deleted rapidly after B cell activation. Although immunization with T-dependent antigens increased BCR signaling, it led to PC reduction and increased apoptosis. Dependent on the antigen, the early GC B cell response was equally reduced and apoptosis increased. At the same time, a higher proportion of GC B cells expressed cMYC, suggesting GC B cell-Tfh cell interactions may be increased. GC B cell numbers returned to normal at later stages, whereas affinity maturation was suppressed in the long term. This confirms that BCR signaling not only directs affinity-dependent B cell selection but also, without adequate further stimulation, can inflict cell death, which may be important for the maintenance of B cell tolerance.
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http://dx.doi.org/10.1016/j.isci.2021.102038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822941PMC
February 2021