Publications by authors named "Shan Gao"

1,081 Publications

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Palmitoylation of SARS-CoV-2 S protein is critical for S mediated syncytia formation and virus entry.

J Med Virol 2021 Sep 16. Epub 2021 Sep 16.

Department of Clinical Laboratory Medicine, The First Affifiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, China.

SARS-CoV-2 causes the ongoing COVID-19 pandemic. S protein is the key viral protein for associating with ACE2, the receptor for SARS-CoV-2. There are many kinds of post-translational modifications in S protein. The mechanism of palmitoylation of SARS-CoV-2 S remains to be elucidated. In our current study, we characterized the palmitoylation of SARS-CoV-2 S. Both the C15 and cytoplasmic tail of SARS-CoV-2 S were palmitoylated. Fatty acid synthase inhibitor C75 and zinc finger DHHC domain-containing palmitoyltransferase (ZDHHC) inhibitor 2-BP reduced the palmitoylation of S. Interestingly, palmitoylation of SARS-CoV-2 S was not required for plasma membrane targeting of S, but was critical for S mediated syncytia formation and SARS-CoV-2 pseudovirus particle entry. Overexpression ZDHHC2, ZDHHC3, ZDHHC4, ZDHHC5, ZDHHC8, ZDHHC9, ZDHHC11, ZDHHC14, ZDHHC16, ZDHHC19 and ZDHHC20 promoted the palmitoylation of S. Furthermore, those ZDHHCs were identified to associate with SARS-CoV-2 S. Our study not only reveals the mechanism of S palmitoylation, but also will shed important light into the role of S palmitoylation in syncytia formation and virus entry. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/jmv.27339DOI Listing
September 2021

The relationship between autophagy-related genes and the staging and prognosis of thyroid cancer: a bioinformatics analysis.

Gland Surg 2021 Aug;10(8):2511-2527

Department of Oncology, Zigong Fourth People's Hospital, Zigong, China.

Background: The number of patients with thyroid cancer is increasing. Autophagy is closely related to thyroid cancer. This study conducted a bioinformatics analysis to examine the relationship between autophagy-related genes and the prognosis of thyroid cancer.

Methods: Based on The Cancer Genome Atlas (TCGA) database, the standardized ribonucleic acid (RNA) sequencing data and corresponding clinical records of 497 patients were obtained. The gene set of autophagy-related genes was obtained from reactom [https://reactome.org/; gene set identification: (R-HSA-1632852)]. Based on the completeness of the sequencing and prognostic data, 135 effective genes were screened to form a gene set. A cluster analysis of the genetic expression of the whole genome was conducted. Different groups and subgroups were defined according to the clustering situation. The relationship between the expression levels of different autophagy-related genes and the clinical characteristics of thyroid cancer were analyzed.

Results: Patients were divided into 2 clusters and 4 subclusters. A comparison of the clinical parameters of the 2 clusters showed that there were differences in node (N)-stage, and a comparison of the 4 subclusters showed that there were differences in age and 4 other characteristics. In relation to the survival comparison, there was a difference in the disease-free survival (DFS) between the 2 clusters, and there was a difference in overall survival (OS) and DFS between subclusters. The 2 clusters had 114 differentially expressed genes (DEGs), and the 4 subclusters had 131 DEGs. In relation to the 5 different factors in each group, there were differences in the distribution of N0N1NX in clusters and subclusters, there were differences in the distribution of M0M1MX in subclusters, and there were differences in the distribution of age and the American Joint Committee on Cancer stage in subclusters. In relation to the stage/N stage/Metastasis (M) stage-related DEGs, 5 common genes were identified: , and . In relation to the stage/N stage/M stage-related DEGs and age-related DEGs 1 common gene was identified: .

Conclusions: Autophagy-related genes are related to the staging of thyroid cancer, but have no clear relationship with long-term prognosis.
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http://dx.doi.org/10.21037/gs-21-480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8411096PMC
August 2021

Influencing factors and strategies of enhancing nanoparticles into tumors .

Acta Pharm Sin B 2021 Aug 24;11(8):2265-2285. Epub 2021 Mar 24.

Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 117004, China.

The administration of nanoparticles (NPs) first faces the challenges of evading renal filtration and clearance of reticuloendothelial system (RES). After that, NPs infiltrate through the expanded endothelial space and penetrated the dense stroma of tumor microenvironment to tumor cells. As long as possible to prolong the time of NPs remaining in tumor tissue, NPs release active agent and induce pharmacological action. This review provides a comprehensive summary of the physical and chemical properties of NPs and the influence of various biological factors in tumor microenvironment, and discusses how to improve the final efficacy through adjusting the characteristics and structure of NPs. Perspectives and future directions are also provided.
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http://dx.doi.org/10.1016/j.apsb.2021.03.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424218PMC
August 2021

A predictive analysis on the risk of peste des petits ruminants in livestock in the Trans-Himalayan region and validation of its transboundary transmission paths.

PLoS One 2021 10;16(9):e0257094. Epub 2021 Sep 10.

College of Wildlife & Protected Area, Northeast Forestry University, Ministry of Education, Harbin, Heilongjiang Province, The People's Republic of China.

Although the Trans-Himalayan region (THR) is an important endemic and rendezvous area of peste des petits ruminants (PPR), monitoring and prevention measurements are difficult to execute because of the rough geographical conditions. Besides, a heterogeneous breeding system and the poor veterinary service of susceptible animals compound the existing problems. Here, we propose a forecasting system to define the key points of PPR prevention and aid the countries in saving time, labor, and products to achieve the goal of the global eradication project of PPR. The spatial distribution of PPR was predicted in the THR for the first time using a niche model that was constructed with a combination of eco-geographical, anthropoid, meteorological, and host variables. The transboundary least-cost paths (LCPs) of small ruminants in the THR were also calculated. Our results reveal that the low-elevation area of the THR had a higher PPR risk and was mainly dominated by human variables. The high-elevation area had lower risk and was mainly dominated by natural variables. Eight LCPs representing corridors among India, Nepal, Bhutan, Bangladesh, and China were obtained. This confirmed the potential risk of transboundary communication by relying on PPR contamination on the grasslands for the first time. The predicted potential risk communication between the two livestock systems and landscapes (high and low elevation) might play a role in driving PPR transboundary transmission.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0257094PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432769PMC
September 2021

Effects of methylenetetrahydrofolate reductase single-nucleotide polymorphisms on breast, cervical, ovarian, and endometrial cancer susceptibilities.

Chronic Dis Transl Med 2021 Sep 12;7(3):169-181. Epub 2021 Aug 12.

Department of Obstetrics and Gynecology, The Shengjing Hospital of China Medical University, Shenyang, Liaoning 110001, China.

Background: Recent studies identifying () polymorphisms associated with breast cancer (BC), ovarian cancer (OC), cervical cancer, and endometrial cancer (EC) have reported conflicting results and been underpowered. To clarify the correlation between mutations and these common female malignancies, we conducted a comprehensive meta-analysis incorporating all eligible publications.

Methods: Relevant reports published before January 20, 2020, were retrieved from PubMed, Embase, the Cochrane Library, and the China National Knowledge Infrastructure databases. The odds ratio and 95% confidence interval summaries for the 677C/T and 1298A/C polymorphisms in BC, OC, cervical cancer, and EC were estimated.

Results: A total of 171 studies comprising 56,675 cancer cases and 67,559 controls were included. The results showed a markedly elevated risk of cancer susceptibility related to 677C/T based on all genetic models. Similarly, we identified a significant correlation between 1298A/C mutation and cancer risk based on overall comparisons among all models, except the heterozygous model. Moreover, subgroup analysis by cancer type revealed a significantly increased risk of BC associated with 677C/T in the five models and of cervical cancer associated with 1298A/C in some models. Based on ethnicity, significant associations were observed between Asian, African, and mixed populations for 677C/T and the Asian population for 1298A/C. With regard to the sample type used for analysis, we detected a positive association between using blood as the DNA source and cancer risk for 677C/T in all genetic models and for 1298A/C in some genetic models. Further stratification of the results revealed that a notably increased risk was associated with the use of polymerase chain reaction-restriction fragment-length polymorphism or TaqMan as the genotyping method, as well as with the use of population-or hospital-based groups as the controls for 677C/T and 1298A/C, respectively.

Conclusion: This meta-analysis suggests that 677C/T and 1298A/C polymorphisms correlate with the risk of common gynecological cancers, with these findings potentially applicable for overall comparisons of related data.
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http://dx.doi.org/10.1016/j.cdtm.2021.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413124PMC
September 2021

Milrinone is better choice for controlled low central venous pressure during hepatectomy: A randomized, controlled trial comparing with nitroglycerin.

Int J Surg 2021 Sep 6;94:106080. Epub 2021 Sep 6.

The First Affiliated Hospital of Sun Yat-sen University, China. Electronic address:

Background: To explore the feasibility and effectiveness of controlled low central venous pressure(CLCVP)induced by milrinone during hepatectomy, and its influence on perioperative hemodynamics, blood loss and patients' recovery, comparing with the traditional method by nitroglycerin.

Methods: 52 patients who underwent elective open hepatectomy were enrolled in the study and randomly divided into two groups: milrinone (M) group and nitroglycerin (NG) group. Milrinone was infused with the rate of 0.5 μg/kg/min in group M, while nitroglycerin was given 0.2-0.5 μg/kg/min in group NG to maintain CVP≤ 5 mmHg during liver resection. The demographic variables, data of the operative procedure and intraoperative hemodynamics were recorded. The postoperative recovery profiles and pre- and post-operative haematological markers of vital organs were also collected and compared.

Results: 1. The blood loss of group M, no matter during liver resection or in the whole procedure, was both less than that of group NG (P < 0.05), so did the hemoglobin detected by blood gas analysis (P < 0.05). Meanwhile, time of hepatectomy and hepatic hilum occlusion were shorter in group M (P < 0.05). 2. Compared with the NG group, cardiac index (CI) and stroke volume index (SVR) were higher in group M in the operation. The norepinephrine dosage necessary in the operation was of no difference in two groups (P > 0.05). 3. Drainage indwelling time and postoperative hospital stay of group M were shorter than that of group NG (P < 0.05). Most of the blood biomarkers increased on postoperative day (POD)-1, and returned to the preoperative level on POD-7 without inter-group difference (P > 0.05). Brain natriuretic peptide precursor (Pro-BNP) in group M was higher than NG group on POD-1 (P < 0.05), and the statistical difference disappeared on POD-7.

Conclusion: Milrinone can effectively maintain a controlled low central venous pressure during hepatectomy. Compared with nitroglycerin, milrinone can reduce the amount of blood loss, with the benefit of better manifestation of hemodynamics and enhanced postoperative recovery.
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http://dx.doi.org/10.1016/j.ijsu.2021.106080DOI Listing
September 2021

A portable thermal detection method based on the target responsive hydrogel mediated self-heating of a warming pad.

Chem Commun (Camb) 2021 Sep 7. Epub 2021 Sep 7.

Key Laboratory of Analysis and Detection for Food Safety (Ministry of Education of China and Fujian Province), Department of Chemistry, Fuzhou University, Fuzhou, 350108, P. R. China.

A simple thermal aptasensing platform was devised for the sensitive detection of organophosphate pesticides (using malathion as a model target) based on the efficient self-heating reaction of a warming pad with a switchable target responsive enzyme-encapsulated three-dimensional (3D) DNA hydrogel using a portable thermometer as a signal readout in this work. The existence of the target malathion would open the catalase-3D network and lots of catalase was released from the hydrogel, which could efficiently convert HO to an O molecule. The product O is the critical condition for the self-heating of the warming pad. Thereafter, the temperature was enhanced with the increasing amount of O. The strategy displays outstanding specificity, reproducibility and stability. Moreover, this method can be easily extended to monitor other molecules using different aptamer sequences in practical applications.
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http://dx.doi.org/10.1039/d1cc03733aDOI Listing
September 2021

The Ferroptosis-NLRP1 Inflammasome: The Vicious Cycle of an Adverse Pregnancy.

Front Cell Dev Biol 2021 20;9:707959. Epub 2021 Aug 20.

Department of Traditional Chinese Medicine, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

One of the hallmarks of placental dysfunction is the increase of oxidative stress. This process, along with the overexpression of the inflammasome, creates a downward spiral that can lead to a series of severe pregnancy complications. Ferroptosis is a form of iron-mediated cell death involving the accumulation of reactive oxygen species, lipid peroxides. In this study, the rats' model of oxidative stress abortion was established, and hydrogen peroxide (HO) was used to establish a cellular model of placental oxidative stress. RNAi, western blot, and immunofluorescence were used to evaluate the expression of specific markers of ferroptosis and the expression of the inflammasome in placental trophoblast cells. We observed excessive levels of ferroptosis and inflammasome activation in both rats' model and placental trophoblast cell model of oxidative stress. When the NLRP1 inflammasome was silenced, the expression levels of GSH and Glutathione peroxidase 4 (GPX4) were increased, while the expression levels of transferrin receptor 1 (TFR1), acyl-CoA synthetase long-chain family member 4 (ACSL4), Superoxide dismutase (SOD), and Malondialdehyde (MDA) were decreased. However, when an NLRP1 activator was applied, we observed the opposite phenomenon. We further explored the mechanisms underlying the actions of ferroptosis to inflammasomes. The expression levels of NLRP1, NLRP3, IL-1β, and caspase-1 were positively correlated with the ferroptosis following the application of ferroptosis inhibitor (ferrostatin-1) and ferroptosis activator (erastin). The existence of ferroptosis was demonstrated in the oxidative stress model of placental trophoblast cells; the results also indicate ferroptosis is linked with the expression of NLRP1 inflammasome. These findings may provide a valuable therapeutic target for the pathogenesis of pregnancy-related diseases.
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http://dx.doi.org/10.3389/fcell.2021.707959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417576PMC
August 2021

Analysis of Gene Expression Profiles, Cytokines, and Bacterial Loads Relevant to Alcoholic Liver Disease Mice Infected With .

Front Immunol 2021 20;12:695491. Epub 2021 Aug 20.

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences (AMMS), Beijing, China.

Patients with liver disease are susceptible to infection with (), but the specific reasons remain elusive. Through RNA-seq, we found that when mice with alcoholic liver disease (ALD) were infected with by gavage, compared with the Pair group, the small intestinal genes affecting intestinal permeability were upregulated; and the number of differentially expressed genes related to immune functions (e.g., such as cell chemotaxis, leukocyte differentiation, and neutrophil degranulation) decreased in the liver, spleen, and blood. Further analysis showed that the number of white blood cells decreased in the Pair group, whereas those in the ALD mice did not change significantly. Interestingly, the blood bacterial load in the ALD mice was about 100 times higher than that of the Pair group. After the ALD mice were infected with , the concentrations of T cell proliferation-promoting cytokines (IL-2, IL-23) decreased. Therefore, unlike the Pair group, ALD mice had weaker immune responses, lower T cell proliferation-promoting cytokines, and higher bacterial loads post-infection, possibly increasing their susceptibility to infection. These new findings we presented here may help to advance the current understanding of the reasons why patients with liver disease are susceptible to infection and provides potential targets for further investigation in the context of treatment options for sepsis in liver disease patient.
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http://dx.doi.org/10.3389/fimmu.2021.695491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417779PMC
August 2021

Characterization of the Genitourinary Microbiome of 1,165 Middle-Aged and Elderly Healthy Individuals.

Front Microbiol 2021 19;12:673969. Epub 2021 Aug 19.

Department of Urology, The Third Affiliated Hospital of Shenzhen University (Luohu Hospital Group), Shenzhen, China.

Accumulated evidence shows that complex microbial communities resides in the healthy human urinary tract and can change in urological disorders. However, there lacks a comprehensive profiling of the genitourinary microbiota in healthy cohort. Here, we performed 16S rRNA gene sequencing of midstream urine specimens from 1,172 middle-aged and elderly healthy individuals. The core microbiota included 6 dominant genera (mean relative abundance >5%), including , , , , , and , and 131 low-abundance genera (0.01-5%), displaying a distinct microbiome profiles to that of host-matched gut microbiota. The composition and diversity of genitourinary microbiome (GM) were distinct between genders and may fluctuate with ages. Several urotypes were identified by the stratification of microbiome profiles, which were mainly dominated by the six most predominant genera. The prevalence of urotypes was disparate between genders, and the male sample additionally harbored other urotypes dominated by , , , or . , , and were co-occurred and co-abundant, and they may play crucial roles as keystone genera and be associated with increased microbial diversity. Our results delineated the microbial structure and diversity landscape of the GM in healthy middle-aged and elderly adults and provided insights into the influence of gender and age to it.
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http://dx.doi.org/10.3389/fmicb.2021.673969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417382PMC
August 2021

Inhibiting PP2Ac Promotes the Malignant Phenotype of Gastric Cancer Cells through the ATM/METTL3 Axis.

Biomed Res Int 2021 24;2021:1015293. Epub 2021 Aug 24.

Department of General Surgery, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing 211100, China.

This article is aimed at exploring the relationship between the phosphatase 2A catalytic subunit C (PP2Ac, encoded by ) and methyltransferase-like 3 (METTL3) in the malignant progression of gastric cancer (GC). Through analyzing the bioinformatics database and clinical tissue immunohistochemistry results, we found that abnormal PP2Ac and METTL3 levels were closely related to the malignant progression of GC. To explore the internal connection between PP2Ac and METTL3 in the progression of GC, we carried out cellular and molecular experiments and finally proved that PP2Ac inhibition can upregulate METTL3 levels by activating ATM activity, thereby promoting the malignant progression of GC.
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http://dx.doi.org/10.1155/2021/1015293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410407PMC
August 2021

Fear-specific leftward bias in gaze direction judgment.

Sci Rep 2021 Sep 2;11(1):17574. Epub 2021 Sep 2.

School of Foreign Languages, University of Electronic Science and Technology of China, Chengdu, 611731, People's Republic of China.

Previous studies have shown that humans have a left spatial attention bias in cognition and behaviour. However, whether there exists a leftward perception bias of gaze direction has not been investigated. To address this gap, we conducted three behavioural experiments using a forced-choice gaze direction judgment task. The point of subjective equality (PSE) was employed to measure whether there was a leftward perception bias of gaze direction, and if there was, whether this bias was modulated by face emotion. The results of experiment 1 showed that the PSE of fearful faces was significantly positive as compared to zero and this effect was not found in angry, happy, and neutral faces, indicating that participants were more likely to judge the gaze direction of fearful faces as directed to their left-side space, namely a leftward perception bias. With the response keys counterbalanced between participants, experiment 2a replicated the findings in experiment 1. To further investigate whether the gaze direction perception variation was contributed by emotional or low-level features of faces, experiment 2b and 3 used inverted faces and inverted eyes, respectively. The results revealed similar leftward perception biases of gaze direction in all types of faces, indicating that gaze direction perception was biased by emotional information in faces rather than low-level facial features. Overall, our study demonstrates that there a fear-specific leftward perception bias in processing gaze direction. These findings shed new light on the cerebral lateralization in humans.
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http://dx.doi.org/10.1038/s41598-021-97039-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413379PMC
September 2021

Light-harvesting complex stress-related proteins play crucial roles in the acclimation of Physcomitrella patens under fluctuating light conditions.

Photosynth Res 2021 Sep 1. Epub 2021 Sep 1.

CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China.

Photosynthetic organisms have evolved photoprotective mechanisms to acclimate to light intensity fluctuations in their natural growth environments. Photosystem (PS) II subunit S (PsbS) and light-harvesting complex (LHC) stress-related proteins (LhcSR) are essential for triggering photoprotection in vascular plants and green algae, respectively. The activity of both proteins is strongly enhanced in the moss Physcomitrella patens under high-light conditions. However, their role in regulating photosynthesis acclimation in P. patens under fluctuating light (FL) conditions is still unknown. Here, we compare the responses of wild-type (WT) P. patens and mutants lacking PsbS (psbs KO) or LhcSR1 and 2 (lhcsr KO) to FL conditions in which the low-light phases were periodically interrupted with high-light pulses. lhcsr KO mutant showed a strong reduction in growth with respect to WT and psbs KO under FL conditions. The lack of LhcSR not only decreased the level of non-photochemical quenching, resulting in an over-reduced plastoquinone pool, but also significantly increased the PSI acceptor limitation values with respect to WT and psbs KO under FL conditions. Moreover, in lhcsr KO mutant, the abundance of PSI core and PSI-LHCI complex decreased greatly under FL conditions compared with the WT and psbs KO. We proposed that LhcSR in P. patens play a crucial role in moss acclimation to dynamic light changes.
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http://dx.doi.org/10.1007/s11120-021-00874-8DOI Listing
September 2021

Faciogenital dysplasia 5 confers the cancer stem cell-like traits of gastric cancer cells through enhancing Sox2 protein stability.

Environ Toxicol 2021 Aug 24. Epub 2021 Aug 24.

Department of Internal Medicine-Cardiovascular, The First People's Hospital of Yuhang District, Hangzhou, China.

The promoting roles of faciogenital dysplasia 5 (FGD5) in tumor progression have been identified in various tumors, however, its roles in gastric cancer progression are still confusing. Currently, it was found that FGD5 was highly expressed in gastric cancer tissues and negatively correlated with different types of survival of gastric cancer patients via online dataset analysis. In vitro analysis of different types of gastric cancer cell lines and normal gastric epithelial cells obtained a consistent result. Then FGD5 was knocked down in gastric cancer cell lines through two independent siRNAs against FGD5 and it was identified that FGD5 knockdown suppressed the cancer stem cell (CSC)-like traits of gastric cancer cells through analyzing the expression of CSC markers, ALDH1 activity and spheroid-formation ability. Further mechanistic studies revealed that FGD5 interacted with Sox2 protein, a critical regulator of CSC progression, enhanced Sox2 protein stability and decreased its ubquitination. Additionally, FGD5 supported the CSC-like traits dependent on Sox2 expression. Taken together, this work identified a novel FGD5/Sox2 axis responsible for the CSC-like traits of gastric cancer cells.
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http://dx.doi.org/10.1002/tox.23355DOI Listing
August 2021

Combination therapy of tanshinone IIA and puerarin for pulmonary fibrosis via targeting IL6-JAK2-STAT3/STAT1 signaling pathways.

Phytother Res 2021 Aug 24. Epub 2021 Aug 24.

State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Efficient therapy of idiopathic pulmonary fibrosis (IPF) is still a major challenge. The current studies with single-target drug therapy are the pessimistic approaches due to the complex characteristics of IPF. Here, a combination therapy of Tanshinone IIA and Puerarin for IPF was proposed to alleviate IPF due to their antiinflammatory and anti-fibrotic effects. In vivo, the combination therapy could significantly attenuate the area of ground glass opacification that was presented by 85% percentile density score of the micro-CT images when compared to single conditions. In addition, the combination therapy enormously improved the survival rate and alleviated pathological changes in bleomycin (BLM)-induced IPF mice. By using a wide spectrum of infiltration biomarkers in immunofluorescence assay in pathological sections, we demonstrate that fewer IL6 related macrophage infiltration and fibrosis area after this combination therapy, and further proved that IL6-JAK2-STAT3/STAT1 is the key mechanism of the combination therapy. In vitro, combination therapy markedly inhibited the fibroblasts activation and migration which was induced by TGF-β1 or/and IL6 through JAK2-STAT3/STAT1 signaling pathway. This study demonstrated that combination therapeutic effect of TanIIA and Pue on IPF may be related to the reduced inflammatory response targeting IL6, which could be an optimistic and effective approach for IPF.
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http://dx.doi.org/10.1002/ptr.7253DOI Listing
August 2021

Nocturnal Sleep Problems Mediate the Impact on Quality of Life of Early Morning Off in Parkinson's Disease.

Front Aging Neurosci 2021 6;13:681773. Epub 2021 Aug 6.

Department of Neurology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Early morning off (EMO) refers to off-states in the morning in people diagnosed with Parkinson's disease (PwPD). This study determined the clinical manifestations of EMO and the association with nocturnal sleep problems and quality of life (QOL) in Chinese PwPD. In this multicenter, observational, cross-sectional study, data concerning the clinical manifestations of EMO were collected from PwPD in Shanghai by questionnaire. The stepwise logistic regression was performed to analyze the potential risk factors, as well as whether EMO was an independent risk factor for functional dependency in daily life. The mediation analyses were conducted to evaluate whether nocturnal sleep problems might mediate the association between EMO and the QOL. Among the 454 subjects evaluated, EMO occurred in 39.43% of PwPD across all disease stages. The prevalence of EMO increased as the Hoehn and Yahr stage increased and was observed in 35.60% of patients in stages 1-2.5 and 48.85% of patients in stages 3-5. EMO was associated with non-motor symptoms (NMSs). The predominant NMSs associated with EMO were nocturnal sleep problems (98.90%), mood/cognition impairment (93.90%), decreased attention/memory (91.60%), gastrointestinal symptoms (91.60%), and urinary urgency (90.50%). The QOL of PwPD with EMO was significantly reduced ( < 0.001). Moreover, nocturnal sleep problems might partially mediate this relationship (indirect effect: β = 13.458, 95% boot CI: 6.436, 22.042). PwPD have EMO throughout all stages of the disease. Patients with EMO have severe motor symptoms and NMSs. EMO decreases the QOL in PwPD and this relationship is partially mediated by nocturnal sleep problems. In light of these findings, it is suggested that recognition and appropriate treatment of EMO and nocturnal sleep problems could improve the management of PwPD.
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http://dx.doi.org/10.3389/fnagi.2021.681773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378267PMC
August 2021

A Motion Capturing and Energy Harvesting Hybridized Lower-Limb System for Rehabilitation and Sports Applications.

Adv Sci (Weinh) 2021 Aug 19:e2101834. Epub 2021 Aug 19.

Department of Electrical and Computer Engineering, National University of Singapore, 4 Engineering Drive 3, Singapore, 117583, Singapore.

Lower-limb motion monitoring is highly desired in various application scenarios ranging from rehabilitation to sports training. However, there still lacks a cost-effective, energy-saving, and computational complexity-reducing solution for this specific demand. Here, a motion capturing and energy harvesting hybridized lower-limb (MC-EH-HL) system with 3D printing is demonstrated. It enables low-frequency biomechanical energy harvesting with a sliding block-rail piezoelectric generator (S-PEG) and lower-limb motion sensing with a ratchet-based triboelectric nanogenerator (R-TENG). A unique S-PEG is proposed with particularly designed mechanical structures to convert lower-limb 3D motion into 1D linear sliding on the rail. On the one hand, high output power is achieved with the S-PEG working at a very low frequency, which realizes self-sustainable systems for wireless sensing under the Internet of Things framework. On the other hand, the R-TENG gives rise to digitalized triboelectric output, matching the rotation angles to the pulse numbers. Additional physical parameters can be estimated to enrich the sensory dimension. Accordingly, demonstrative rehabilitation, human-machine interfacing in virtual reality, and sports monitoring are presented. This developed hybridized system exhibits an economic and energy-efficient solution to support the need for lower-limb motion tracking in various scenarios, paving the way for self-sustainable multidimensional motion tracking systems in near future.
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http://dx.doi.org/10.1002/advs.202101834DOI Listing
August 2021

[The Significance of CD319 and CD269 in the Detection of Immunophenotyping and Minimal Residual Disease in Multiple Myeloma Patients].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021 Aug;29(4):1195-1202

Department of Hematology, Jishuitan Hospital, Beijing 100096, China E-mail

Objective: To investigate the expression of CD319 and CD269 in plasma cells of patients with multiple myeloma (MM) and the feasibility of using CD319 instead of CD38 as a gating antigen in immunophenotyping and minimal residual disease (MRD) monitoring.

Methods: The expression levels of CD319 and CD269 antigens in clonal bone marrow plasma cells of 387 patients were detected by CD38/CD138 gating strategy with 8-color flow cytometry, and the stability of antigens was also analyzed, and the sensitivity and correlation of two different gating strategies employing CD319/CD138 and CD38/CD138 were compared as well. The control group consisted of 53 cases with non-malignant blood disease matched by age and sex.

Results: Monoclonal plasma cells were detected in 303 of 387 MM patients, among which 277 cases (91.42%) were positive for CD269, and all cases were positive for CD319 (100%). In newly diagnosed MM (NDMM) and recurrent refractory MM (RRMM) patients, the expression levels of CD269 were 97.53% (0-99.92%) and 94.96% (0.22%-99.99%), respectively, while levels of CD319 were 99.90% (87.77%-100%) and 99.78% (63.12%-100%), respectively. The expression levels of CD269 and CD319 in the control group were 97.00% (77.00%-100%) and 100% (89.00%-100%), respectively. There were no significant differences in the expression levels of CD269 and CD319 among NDMM, RRMM and the control group. Patients acquiring therapeutic effects were divided into complete remission (CR) group, very good partial response (VGPR) group and partial response (PR) group. Gating with CD38/CD138, median MRD values were 0.76% (0-1.88%), 0.77% (0-4.96%) and 1.75% (0.09%-10.90%) in the three groups, respectively, while gating with CD319/CD138, median MRD values were 0.57% (0.18%-1.96%), 1.07% (0.12%-4.85%) and 1.77% (0.08%-8.22%), respectively. There was no significant difference in MRD level by the two gating strategies, but a good correlation between the two (r=0.808, P<0.05). In addition, in 4 patients treated by CD38 monoclonal antibody (DARA), the expression level of CD38 was observed to be down-regulated or even negative after treatment. When the MRD level was very low, CD38/CD138 gating resulted in false MRD, while CD319/CD138 gating resulted in MRD.

Conclusion: CD319 and CD269 express stably and continuously in plasma cells of MM patients at different disease stages. CD319 can be used as an alternative of CD38 for immunophenotyping and MRD detection, especially for MRD detection after DARA treatment, while CD269 is suitable for detection before BCMA-CAR-T treatment.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2021.04.027DOI Listing
August 2021

How Does Risk-Information Communication Affect the Rebound of Online Public Opinion of Public Emergencies in China?

Int J Environ Res Public Health 2021 07 22;18(15). Epub 2021 Jul 22.

School of Public Administration, Central South University, Changsha 410083, China.

The rebound of online public opinion is an important driving force in inducing a secondary crisis in the case of public emergencies. Effective risk-information communication is an important means to manage online public opinion regarding emergencies. This paper employs fuzzy-set qualitative comparative analysis to discover which conditions are combined and may result in the rebound of online public opinion. Five conditions were selected: the type of public emergency, messengers, message attributes, audience, and information feedback. The study used a sample of 25 major public emergencies that occurred between 2015 and 2020 in China. The type of public emergency, audience, and information feedback emerged as critical influencing factors. Message attributes promote the rebound of online public opinion regarding public health emergencies, while messengers play a traction role in the rebound of online public opinion on other types of public emergencies. This study extends risk-information communication theory from the perspective of the type of emergency, explores the causes of rebounded online public opinion regarding public emergencies, and provides policies and suggestions for risk-information communication and online public-opinion governance during emergencies.
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http://dx.doi.org/10.3390/ijerph18157760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345355PMC
July 2021

Nanotechnology for Boosting Cancer Immunotherapy and Remodeling Tumor Microenvironment: The Horizons in Cancer Treatment.

ACS Nano 2021 Aug 2. Epub 2021 Aug 2.

Department of Pharmaceutics, School of Pharmaceutical Sciences, Shandong University, 44 WenhuaXilu, Jinan 250012, China.

Immunotherapy that harnesses the human immune system to fight cancer has received widespread attention and become a mainstream strategy for cancer treatment. Cancer immunotherapy not only eliminates primary tumors but also treats metastasis and recurrence, representing a major advantage over traditional cancer treatments. Recently with the development of nanotechnology, there exists much work applying nanomaterials to cancer immunotherapy on the basis of their excellent physiochemical properties, such as efficient tissue-specific delivery function, huge specific surface area, and controllable surface chemistry. Consequently, nanotechnology holds significant potential in improving the efficacy of cancer immunotherapy. Nanotechnology-based immunotherapy mainly manifests its inhibitory effect on tumors two different approaches: one is to produce an effective anti-tumor immune response during tumorigenesis, and the other is to enhance tumor immune defense ability by modulating the immune suppression mechanism in the tumor microenvironment. With the success of tumor immunotherapy, understanding the interaction between the immune system and smart nanomedicine has provided vigorous vitality for the development of cancer treatment. This review highlights the application, progress, and prospect of nanomedicine in the process of tumor immunoediting and also discusses several engineering methods to improve the efficiency of tumor treatment.
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http://dx.doi.org/10.1021/acsnano.1c02103DOI Listing
August 2021

Xin-Ji-Er-Kang protects myocardial and renal injury in hypertensive heart failure in mice.

Phytomedicine 2021 Jul 18;91:153675. Epub 2021 Jul 18.

Department of Pharmacology, Basic Medical College, Anhui Medical University, Hefei 230032, China. Electronic address:

Background: Xin-Ji-Er-Kang (XJEK) as a herbal formula of traditional Chinese medicine (TCM) has shown the protective effects on myocardial function as well as renal function in mouse models of myocardial infarction.

Hypothesis/purpose: We investigated the effects of XJEK on cardiovascular- and renal-function in a heart failure mouse model induced by high salt (HS) and the associated mechanisms.

Study Design: For the purpose of assessing the effects of XJEK on a hypertensive heart failure model, mice were fed with 8% high salt diet. XJEK was administered by oral gavage for 8 weeks. Cardiovascular function parameters, renal function associated biomarkers and XJEK's impact on renin-angiotensin-aldosterone system (RAAS) activation were assessed. To determine the underlying mechanism, the calpain1/junctophilin-2 (JP2)/sarcoplasmic reticulum Ca ATPase (SERCA2a) pathway was further studied in AC16 cells after angiotensin II-challenge or after calpastatin small interfering RNA (siRNA) transfection.

Results: Mice on HS-diet exhibited hypertensive heart failure along with progressive kidney injury. Similar to fosinopril, XJEK ameliorated hypertension, cardiovascular-and renal- dysfunction in mice of HS-diet group. XJEK inhibited HS-induced activation of RAAS and reversed the abnormal expression pattern of calpain1and JP2 protein in heart tissues. XJEK significantly improved cell viability of angiotensin II-challenged AC16 cells. Moreover, XJEK's impact on calpain1/JP2 pathway was partly diminished in AC16 cells transfected with calpastatin siRNA.

Conclusion: XJEK was found to exert cardiovascular- and renal protection in HS-diet induced heart failure mouse model. XJEK inhibited HS-diet induced RAAS activation by inhibiting the activity and expression of calpain1 and protected the junctional membrane complex (JMC) in cardiomyocytes.
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http://dx.doi.org/10.1016/j.phymed.2021.153675DOI Listing
July 2021

Asymmetric synthesis of chiral organosilicon compounds via transition metal-catalyzed stereoselective C-H activation and silylation.

Chem Commun (Camb) 2021 Aug 29;57(67):8250-8263. Epub 2021 Jul 29.

College of Chemistry and Chemical Engineering and Key Laboratory of Functional Small Organic Molecules, Ministry of Education, Jiangxi Normal University (Yaohu Campus), 99 Ziyangdadao Avenue, Nanchang, Jiangxi 330022, China.

This feature article details the progress of transition metal-catalyzed stereoselective sp and sp C-H activation and silylation in the synthesis of chiral organosilicon compounds, and the asymmetric C-H silylation includes intramolecular cyclizing silylation and intermolecular silylation. The silylating reagents include monohydrosilanes, dihydrosilanes, silacylcobutanes and disilanes. In general, catalytic systems include a transition metal salt as the catalyst and a chiral ligand. No external chiral ligand is required in some cases where the chiral substrates act as the source of chirality. Many kinds of silylated compounds with central, axial, planar, or helical chirality have been constructed via C-H activation by asymmetric rhodium, iridium or palladium catalysis. Some pharmacophores and material building blocks were successfully introduced into the target molecules. Some silylated products proved to be useful in medicinal chemistry, synthetic organic chemistry, and materials science. Besides reaction development, mechanisms for stereoselective C-H activation and silylation are also discussed.
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http://dx.doi.org/10.1039/d1cc02839aDOI Listing
August 2021

Advances in autophagy as a target in the treatment of tumours.

J Drug Target 2021 Aug 12:1-22. Epub 2021 Aug 12.

Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, PR China.

Autophagy is a multi-step lysosomal degradation process, which regulates energy and material metabolism and has been used to maintain homeostasis. Autophagy has been shown to be involved in the regulation of health and disease. But at present, there is no consensus on the relationship between autophagy and tumour, and we consider that it plays a dual role in the occurrence and development of tumour. That is to say, under certain conditions, it can inhibit the occurrence of tumour, but it can also promote the process of tumour. Therefore, autophagy could be used as a target for tumour treatment. The regulation of autophagy plays a synergistic role in the radiotherapy, chemotherapy, phototherapy and immunotherapy of tumour, and nano drug delivery system provides a promising strategy for improving the efficacy of autophagy regulation. This review summarised the progress in the regulatory pathways and factors of autophagy as well as nanoformulations as carriers for the delivery of autophagy modulators.
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http://dx.doi.org/10.1080/1061186X.2021.1961792DOI Listing
August 2021

Monomeric C-reactive protein promotes platelets to release mitochondrial DNA in anti-neutrophil cytoplasmic antibody-associated vasculitis.

Mol Immunol 2021 09 19;137:228-237. Epub 2021 Jul 19.

Department of Nephrology, Tianjin Medical University General Hospital, Tianjin, 300052, China. Electronic address:

Although high level of circulating C-reactive protein (pCRP) is considered as a biomarker for disease activity, the significance of CRP in the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has not been clarified. We once reported in AAV, pentameric CRP (pCRP) could dissociate into monomeric CRP (mCRP) and activate platelets. Recent studies have demonstrated that the activated platelets can release mitochondrial DNA (mtDNA). The purpose of this study was to further study the relationship between mCRP and platelets in AAV. We found the plasma level of mCRP in AAV patients was significantly higher than that of normal control and positively correlated with the proportion of mCRP-positive platelets. Platelets isolated from one normal donor could be activated by plasma from 5 AAV patients and this effect could be attenuated when mCRP had been removed. Only 0.1 μg/mL of recombinant mCRP was needed for inducing platelets to release mtDNA via interaction with lipid raft and through p38 MAPK/NF-κB pathway. The mCRP binding on platelets depended on the C-terminal octapeptide (aa 199-206). The released mtDNA did not induce respiratory burst alone, but enhanced the ANCA-induced neutrophils respiratory burst after binding Toll-like receptor 9 (TLR9). The mtDNA released by mCRP-activated platelets also enhanced thrombin generation of plasma. In conclusion, our data demonstrate that mCRP can bind platelets via interaction with lipid raft and induce the release of mtDNA. The released mtDNA can enhance the pathogenicity of ANCA and promote activation of coagulation system in AAV.
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http://dx.doi.org/10.1016/j.molimm.2021.07.007DOI Listing
September 2021

RHBDF1 promotes AP-1-activated endothelial-mesenchymal transition in tumor fibrotic stroma formation.

Signal Transduct Target Ther 2021 Jul 19;6(1):273. Epub 2021 Jul 19.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, China.

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http://dx.doi.org/10.1038/s41392-021-00597-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286969PMC
July 2021

Low incidence rate of diarrhoea in COVID-19 patients is due to integrin.

J Infect 2021 Jul 15. Epub 2021 Jul 15.

Department of Laboratory Medicine, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China; School of Basic Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China; Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China. Electronic address:

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http://dx.doi.org/10.1016/j.jinf.2021.07.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280609PMC
July 2021

Potential of C-X-C motif chemokine ligand 1/8/10/12 as diagnostic and prognostic biomarkers in idiopathic pulmonary arterial hypertension.

Clin Respir J 2021 Jul 14. Epub 2021 Jul 14.

Department of Respiratory Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.

Objective: This study aimed to evaluate the clinical role of C-X-C motif chemokine ligand (CXCL) family members in idiopathic pulmonary arterial hypertension (IPAH) patients.

Methods: CXCL1, CXCL8, CXCL10 and CXCL12 expressions in the serum samples of IPAH patients (N=39) and age/gender-matched controls (N=40) were detected by enzyme-linked immunosorbent assay. In IPAH patients, clinical features were collected and survival information was documented.

Results: CXCL1 (P<0.001), CXCL8 (P=0.001), CXCL10 (P<0.001) and CXCL12 (P<0.001) were increased in IPAH patients compared with controls, and receiver's operating characteristic curves showed that their combination was highly correlated with IPAH risk (area under curve: 0.881, 95% confidence interval: 0.805-0.958). Meanwhile, CXCL1 was positively correlated with mean pulmonary artery pressure (mPAP) (P=0.029) and high sensitive C-reactive protein (HsCRP) (P=0.015); CXCL8 was positively correlated with mPAP (P=0.044) and HsCRP (P=0.018) but negatively correlated with 6-minute walk test (6MWT) distance (P=0.029); CXCL10 was positively correlated with mean right artery pressure (P=0.002); and CXCL12 was positively correlated with World Health Organization functional class (P=0.047), mPAP (P=0.009), pulmonary vascular resistance (P=0.004), HsCRP (P=0.003) but negatively correlated with 6MWT distance (P=0.003) in IPAH patients. Moreover, CXCL12 was negatively correlated with overall survival (OS) (P=0.025), while CXCL1, CXCL8 and CXCL10 only showed minor tendencies to be negatively correlated with OS in IPAH patients without statistical significance (all P>0.05).

Conclusion: CXCL1, CXCL8, CXCL10 and CXCL12 associate with increased IPAH risk, unfavorable clinical features; besides, CXCL12 correlates with worse OS in IPAH patients.
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http://dx.doi.org/10.1111/crj.13421DOI Listing
July 2021

SUMOylation modification-mediated cell death.

Open Biol 2021 Jul 14;11(7):210050. Epub 2021 Jul 14.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, No.17, 3rd Section of People's South Road, Chengdu, 610041, People's Republic of China.

SUMOylation dynamically conjugates SUMO molecules to the lysine residue of a substrate protein, which depends on the physiological state of the cell and the attached SUMO isoforms. A prominent role of SUMOylation in molecular pathways is to govern the cellular death process. Herein, we summarize the association between SUMOylation modification events and four types of cellular death processes: apoptosis, autophagy, senescence and pyroptosis. SUMOylation positively or negatively regulates a certain cellular death pattern depending on specific conditions including the attached SUMO isoforms, disease types, substrate proteins and cell context. Moreover, we also discuss the possible role of SUMOylation in ferroptosis and propose a potential role of the SUMOylated GPX4 in the regulation of ferroptosis. Mapping the exact SUMOylation network with cellular death contributes to develop novel SUMOylation-targeting disease therapeutic strategies.
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http://dx.doi.org/10.1098/rsob.210050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277462PMC
July 2021

Tai Chi for Improving Chronic Primary Musculoskeletal Pain: Protocol for a Systematic Review.

Evid Based Complement Alternat Med 2021 21;2021:9932336. Epub 2021 Jun 21.

Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

. Chronic primary musculoskeletal pain (CPMP) is a major health problem that has physical and psychological impacts as well as an associated economic burden. Currently, pharmacological treatment remains unsatisfactory because of side effects and potential misuse. Therefore, nonpharmacological approaches for pain are being actively explored, and Tai Chi has attracted increased attention as a therapy for pain. Although clinical trials have shown that Tai Chi may be effective in treating CPMP, no systematic review has clarified its effectiveness and safety. The objective of this systematic review is to assess the effect and safety of Tai Chi for patients suffering from CPMP. . We will search relevant electronic databases from inception to May 31, 2021: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, the Wanfang database, the Chongqing VIP database, and China Biology Medicine Disc. Studies comparing the use of Tai Chi with other managements for CPMP patients will be included. Our review will include studies that measured change in pain intensity as the primary outcome using patient-reported ratings (visual analog scale or numerical rating scale). Hospital Anxiety and Depression Scale scores, SF-36 Health Survey scores, Pittsburgh Sleep Quality Index scores, and adverse effects will be explored as secondary outcomes. The risk of bias and the reporting quality of included studies will be evaluated using the Cochrane Collaboration risk-of-bias assessment method. The data will be analyzed using RevMan v5.3 software. . This study protocol was registered on PROSPERO. The registration number for this protocol is CRD42020165048.
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http://dx.doi.org/10.1155/2021/9932336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238584PMC
June 2021

[Revealing the mechanisms underlying the therapeutic effects of acupuncture on migraine using neuroimaging: a narrative review].

Sheng Li Xue Bao 2021 Jun;73(3):433-445

Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China.

Migraine is a neurological disorder characterized by attacks of moderate or severe headache and various neurological symptoms. Acupuncture, as a commonly used non-pharmacological therapy, has the advantage of obvious therapeutic effect and few side effects in the prevention and treatment of migraine. But the underlying mechanism of acupuncture on migraine remains unclear. Recently, advances in neuroimaging technology have helped to objectively assess the effect of acupuncture on treating migraine and offered new opportunities to explore the central mechanism of acupuncture on treating migraine. In order to better understand the current status of neuroimaging studies on the therapeutic mechanism of acupuncture on migraine and shed light on future research, this review aims to overview the neuroimaging studies in recent 10 years from two aspects: (1) Central mechanism of acupuncture on treating acute migraine attack; (2) Central mechanism of acupuncture on preventing migraine attack.
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June 2021
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