Publications by authors named "Shanshan Li"

1,389 Publications

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Sustained air pollution exposures, fasting plasma glucose, glycated haemoglobin, prevalence and incidence of diabetes: a nationwide study in China.

Int J Epidemiol 2022 Aug 10. Epub 2022 Aug 10.

Department of Global Health, School of Public Health, Wuhan, China.

Background: Evidence remains limited and inconsistent for the associations between sustained air pollution exposures and diabetes development. This study aimed to determine the potential effects of particulate matter with a diameter of ≤10 micrometres (PM10), particulate matter with a diameter of ≤2.5 micrometres (PM2.5) and nitrogen dioxide (NO2) on alterations of fasting plasma glucose (FPG), glycated haemoglobin (HbA1c), in particular, on prevalence and incidence of diabetes.

Methods: Cross-sectional analyses were conducted based on 9628 participants aged ≥45 years from the baseline survey (2011) of the China Health and Retirement Longitudinal Study (CHARLS), whereas cohort analyses were based on 3510 individuals without diabetes at baseline in the third survey (2015). Residences of participants were geocoded and the air pollution exposures were estimated using a satellite-based spatiotemporal model. Linear, logistic and modified Poisson regression models, adjusting for multiple confounders, were applied to assess the associations between air pollution and FPG, HbA1c, prevalence and incidence of diabetes, respectively.

Results: Associations between PM10, PM2.5 and increased levels of FPG and HbA1c were identified. The levels of FPG and HbA1c increased by 0.025 mmol/L (95% CI: 0.007, 0.044) and 0.011 mmol/L (95% CI: 0.002, 0.019), respectively, for a 10-μg/m3 increase in PM10, and the levels of FPG and HbA1c increased by 0.061 mmol/L (95% CI: 0.028, 0.096) and 0.016 mmol/L (95% CI: 0.000, 0.031), respectively, for a 10-μg/m3 increase in PM2.5. There were also positive associations between diabetes prevalence and PM2.5 and PM10. In the cohort analyses, PM10, PM2.5 and NO2 were associated with a higher incidence of diabetes.

Conclusion: Air pollution was allied to diabetes development in elderly Chinese populations. Considering the impact of the dramatic increase in the incidence and prevalence of diabetes in China, interventions to improve air quality are urgently needed.
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http://dx.doi.org/10.1093/ije/dyac162DOI Listing
August 2022

Identification of pellicle formation related microorganisms in traditional Sichuan paocai through metagenomic sequence and the effects of Baijiu/Salt on pellicle and volatile components.

Food Res Int 2022 Sep 23;159:111130. Epub 2022 Apr 23.

College of Food Science, Sichuan Agricultural University, Ya'an 625014, PR China. Electronic address:

The occurrence of pellicle on the surface of paocai brine is a common undesirable phenomenon during the multi-rounds of paocai fermentation, which is mainly caused by the growth of microorganisms related to pellicle formation. But the detailed information on these microorganisms and volatile components produced by them, as well as the changes of the microorganisms during the process of paocai recovery, are still rare in the literature. Therefore, the purpose of this study was (1) to analyze the pellicle formation related microorganisms by comparing the differential microorganisms in initial brine and the brine when pellicle occurred through metagenomic sequencing technology, (2) to explore the changes of microorganisms in the fermentation system after addition Baijiu and/or salt, and (3) to further detect the VOCs in paocai samples by gas chromatography-mass spectrometry (GC-MS). The relationship between VOCs and the selected marker microorganisms was also determined. The results showed that the diversity of fungi was increased when pellicle formed, the pellicle formation related microorganisms mainly belonged to six genus, including Kazachstania, Lactobacillus, Pichia, Candida, Lachancea, and Saccharomyces. Apart from the unknown function and basic life activities of microorganisms, the metabolic activities of these pellicle formation related microorganisms were mainly carbohydrate transport and metabolism, and amino acid transport and metabolism. The growth of pellicle formation related microorganisms could be inhibited by adding Baijiu (1.5% v/v), but the addition of salt (7% salt (w/v) did not promote this inhibitory effect. Through PCA analysis, it was found that the VOCs of paocai were significantly affected by adding Baijiu and Baijiu and salt. The undesirable smell at the beginning of pellicle formation may be related to Propanoic acid, hexyl ester, 1,3-Dimethyl-1-cyclohexene, Oxime-, methoxy-phenyl- and Phenylethyl Alcohol.
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http://dx.doi.org/10.1016/j.foodres.2022.111130DOI Listing
September 2022

Clearance of multiple cutaneous warts by targeting a single lesion: a randomized comparative evaluation of mild local hyperthermia versus cryotherapy.

J Am Acad Dermatol 2022 Aug 4. Epub 2022 Aug 4.

Department of Dermatology, The First Hospital of China Medical University, Shenyang, China; Key Laboratory of Immunodermatology, Ministry of Education and NHC; National joint Engineering Research Center for Theranostics of Immunological Skin Diseases, Shenyang, China. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2022.07.043DOI Listing
August 2022

High ambient temperature and risk of hospitalization for gastrointestinal infection in Brazil: A nationwide case-crossover study during 2000-2015.

Sci Total Environ 2022 Aug 4;849:157836. Epub 2022 Aug 4.

Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne 3004, Australia; Climate, Air Quality Research Unit, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. Electronic address:

Background: The burden of gastrointestinal infections related to hot ambient temperature remains largely unexplored in low-to-middle income countries which have most of the cases globally and are experiencing the greatest impact from climate change. The situation is particularly true in Brazil.

Objectives: Using medical records covering over 78 % of population, we quantify the association between high temperature and risk of hospitalization for gastrointestinal infection in Brazil between 2000 and 2015.

Methods: Data on hospitalization for gastrointestinal infection and weather conditions were collected from 1814 Brazilian cities during the 2000-2015 hot seasons. A time-stratified case-crossover design was used to estimate the association. Stratified analyses were performed by region, sex, age-group, type of infection and early/late study period.

Results: For every 5 °C increase in mean daily temperature, the cumulative odds ratio (OR) of hospitalization over 0-9 days was 1.22 [95 % confidence interval (CI): 1.21, 1.23] at the national level, reaching its maximum in the south and its minimum in the north. The strength of association tended to decline across successive age-groups, with infants < 1 year most susceptible. The effect estimates were similar for men and women. Waterborne and foodborne infections were more associated with high temperature than the 'others' and 'idiopathic' groups. There was no substantial change in the association over the 16-year study period.

Discussion: Our findings indicate that exposure to high temperature is associated with increased risk of hospitalization for gastrointestinal infection in the hot season, with the strength varying by region, population subgroup and infection type. There was no evidence to indicate adaptation to heat over the study duration.
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http://dx.doi.org/10.1016/j.scitotenv.2022.157836DOI Listing
August 2022

DRDB: A Machine Learning Platform to Predict Chemical-Protein Interactions towards Diabetic Retinopathy.

Oxid Med Cell Longev 2022 20;2022:1718353. Epub 2022 Jul 20.

Cloudphar Pharmaceuticals Co., Ltd., Shenzhen, China.

Diabetic retinopathy (DR), a diabetic microangiopathy caused by diabetes, affects approximately 93 million people, worldwide. However, the drugs used to treat DR have limited efficacy and the variety of side effects. This is possibly because the complicated pathogenesis of DR is associated with multiple proteins. In this work, we attempted to identify potential drugs against DR-associated proteins and predict potential targets for drugs using in silico prediction of chemical-protein interactions (CPI) based on multitarget quantitative structure-activity relationship (mt-QSAR) method. Therefore, we developed 128 binary classifiers to predict the CPI for 15 DR targets using random forest (RF), -nearest neighbours (KNN), support vector machine (SVM), and neural network (NN) algorithms with MACCS, extended connectivity fingerprints (ECFP6) fingerprints, and protein descriptors. In order to facilitate discovery of the novel drugs and target identification using the 128 binary classifiers, a free web server (DRDB) was developed. Compound Danshen Dripping Pills (CDDP), composed of Salvia miltiorrhiza, Panax notoginseng, and borneol, is commonly used in the treatment of cardiovascular diseases. To explore the applicability of DRDB, the potential CPIs of CDDP in treatment of DR were investigated based on DRDB. In vitro experimental validation demonstrated that cryptotanshinone and protocatechuic acid, two key components of CDDP, are capable of targeting ICAM-1 which is one of the key target of DR. We hope that this work can facilitate development of more effective clinical strategies for the treatment of DR.
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http://dx.doi.org/10.1155/2022/1718353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329024PMC
August 2022

Influence of the Driving Pressure on Mortality in ARDS Patients with or without Abdominal Obesity: A Retrospective Cohort Study.

Contrast Media Mol Imaging 2022 15;2022:1219666. Epub 2022 Jul 15.

Zhongshan Hospital, Fudan University, Shanghai 200032, China.

Objective: This study sets out to explore if the relationship between the driving pressure and hospital mortality in ARDS patients is influenced by body mass index (BMI) level or the presence of abdominal obesity.

Methods: Data were extracted from an online database named "Multiparameter Intelligent Monitoring in Intensive Care III." A total of 1556 patients were included and divided into four subgroups based on both BMI level (BMI ≥30 kg/m or BMI <30 kg/m) and abdominal assessment. Driving pressure [i.e., the difference between plateau pressure and positive end-expiratory pressure (PEEP)] within 24 h of invasive mechanical ventilation was compared between survivors and nonsurvivors during hospitalization in each group. A logistic regression model was used for hospital mortality.

Results: There were 1556 patients with mild-to-severe ARDS, 666 (42.80%) nonobese patients with nonabdominal obesity, 259 (16.65%) nonobese patients with abdominal obesity, 97 (6.23%) obese patients with nonabdominal obesity, and 534 (34.32%) obese patients with abdominal obesity. Driving pressure in nonobese patients with nonabdominal obesity was significantly lower in survivors (12.77 ± 4.53 cm HO) than in nonsurvivors (14.26 ± 5.52 cm HO, < 0.01). On the contrary, in the other three groups, driving pressure was not significantly different between survivors and nonsurvivors. After a logistic multivariable regression analysis, in nonobese (BMI<30 kg/m) patients with nonabdominal obesity, the driving pressure was independently associated with increased hospital mortality (OR: 1.04, 95% CI 1.00-1.09, < 0.05) but not in the other three subgroups.

Conclusion: Driving pressure is associated with increase in hospital mortality only in nonobese (BMI <30 kg/m) patients with nonabdominal obesity.
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http://dx.doi.org/10.1155/2022/1219666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9307407PMC
August 2022

OL-FS13 alleviates experimental cerebral ischemia-reperfusion injury.

Exp Neurol 2022 Jul 25;357:114180. Epub 2022 Jul 25.

Department of Anatomy and Histology & Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming 650500, Yunnan, China. Electronic address:

Cerebral ischemia-reperfusion (I/R) is the main cause of neurological injury after stroke. However, existing treatments for I/R injury are relatively poor, and relevant drugs need to be further explored. Amphibians have received increasing attention as a resource bank of bioactive peptides. However, reports on neuroprotective peptides from amphibians remain extremely rare. Here, we identified a new neuroprotective peptide (OL-FS13, amino acid sequence: FSLLLTWWRRRVC) from the odorous frog species Odorrana livida using a constructed cDNA library. OL-FS13 significantly improving infarct volume, behavioral and histological abnormalities in rats, and also showed neuroprotective activities in PC12 cell (by oxygen glucose deprivation/reoxygenation, OGD/R). Mechanistically, OL-FS13 increased the level of antioxidative enzymes to resist oxidative stress and alleviated endoplasmic reticulum (ER) stress induced by I/R and OGD/R. The use of ML385 (Nrf2 inhibitor) indicated that OL-FS13 relieved nerve damage caused by oxidative and ER stress by increasing the nuclear displacement of Nrf2. Collectively, this research provides a novel drug candidate for the clinical cerebral I/R curation.
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http://dx.doi.org/10.1016/j.expneurol.2022.114180DOI Listing
July 2022

Antibacterial Peptide NP-6 Affects by Multiple Modes of Action.

Int J Mol Sci 2022 Jul 15;23(14). Epub 2022 Jul 15.

College of Food Science, Sichuan Agricultural University, Ya'an 625014, China.

Our previous study extracted and identified an antibacterial peptide that was named NP-6. Herein, we investigated the physicochemical properties of NP-6, and elucidated the mechanisms underlying its antimicrobial activity against . The results showed that the hemolysis activity of NP-6 was 2.39 ± 0.13%, lower than Nisin A (3.91 ± 0.43%) at the same concentration (512 µg/mL). Negligible cytotoxicity towards RAW264.7 cells was found when the concentration of NP-6 was lower than 512 µg/mL. In addition, it could keep most of its activity in fetal bovine serum. Moreover, transmission electron microscopy, confocal laser scanning microscopy, and flow cytometry results showed that NP-6 can destroy the integrity of the bacterial cell membrane and increase the membrane permeability. Meanwhile, NP-6 had binding activity with bacterial DNA and RNA in vitro and strongly inhibited the intracellular β-galactosidase activity of . Our findings suggest that NP-6 could be a promising candidate against .
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http://dx.doi.org/10.3390/ijms23147812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319634PMC
July 2022

Transition between Mycobacterium tuberculosis and nontuberculous mycobacteria in recurrent "tuberculosis" patients.

Eur J Clin Microbiol Infect Dis 2022 Aug 26;41(8):1127-1132. Epub 2022 Jul 26.

Department of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Postal No 9, Beiguan Street, Tongzhou District, Beijing, 101149, People's Republic of China.

Recurrence of tuberculosis (TB) is still a key issue in the control of tuberculosis. The presence of nontuberculous mycobacteria (NTM) complicates the diagnosis of recurrent TB due to similarity in clinical presentation. Herein, we have used molecular genotyping methods to identify mycobacteria species, and analyzed the characteristics of patients with transition between MTB and NTM. Eighty-nine patients with recurrent tuberculosis over the past 12 years were included in our analysis. We found that 9 patients had NTM infections during the study period. Six patients were infected with different mycobacterial strains, half of which were transformed from NTM to MTB, and the other half from MTB to NTM. In addition, the other 3 patients were infected with the same NTM species. Further WGS analysis showed that only one patient had a relapse and the remaining two were classified as reinfection. In conclusion, our results demonstrate that a proportion of previously diagnosed recurrent TB cases are attributed to the transition between MTB and NTM, highlighting the significance of species identification prior to initiation of treatment. The recurrence of mycobacterial diseases is majorly noted within 1 year after treatment completion.
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http://dx.doi.org/10.1007/s10096-022-04477-6DOI Listing
August 2022

Exploration of the amino acid metabolic signature in anthracycline-induced cardiotoxicity using an optimized targeted metabolomics approach based on UPLC-MS/MS.

Naunyn Schmiedebergs Arch Pharmacol 2022 Jul 26. Epub 2022 Jul 26.

Department of Clinical Laboratory, Peking University People's Hospital, No. 11 Xizhimen South Street, Beijing, 100044, People's Republic of China.

Although anthracyclines improve the long-term survival rate of patients with cancer, severe and irreversible myocardial damage limits their clinical application. Amino acid (AA) metabolism in cardiomyocytes can be altered under pathological conditions. Therefore, exploring the AA metabolic signature in anthracycline-induced cardiotoxicity (AIC) is important for identifying novel mechanisms. We established mouse and cellular models of Adriamycin (ADR)-induced cardiac injury. We observed a decreased expression of troponins I (cTnI) after ADR treatment and ADR accelerated the degradation of cTnI, implying that AA metabolism could be altered in AIC. Using a targeted AA metabolomics approach based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), the AA metabolic signatures in the sera of AIC mice and supernatant samples of ADR-treated H9c2 cardiomyocytes were analyzed. The levels of 14 AA metabolites were altered in ADR-treated mice (p < 0.05). Via bioinformatics analysis, we identified nine differential AA metabolites in mice and five differential AA metabolites in ADR-treated H9c2 cardiomyocytes. Three AAs with increased levels (L-glutamate, L-serine, and L-tyrosine) overlapped in the two models, suggesting a possible mechanism of AA metabolic impairment during AIC. The metabolic pathways perturbed by AIC involved aminoacyl-tRNA biosynthesis and alanine, aspartate, and glutamate metabolism. Our data suggests that ADR perturbed AA metabolism in AIC models. Moreover, the targeted AA metabolomics approach based on UPLC-MS/MS can be a unique platform to provide new clues for the prevention and treatment of AIC.
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http://dx.doi.org/10.1007/s00210-022-02271-xDOI Listing
July 2022

Circular RNA ROCK1, a novel circRNA, suppresses osteosarcoma proliferation and migration via altering the miR-532-5p/PTEN axis.

Exp Mol Med 2022 Jul 25;54(7):1024-1037. Epub 2022 Jul 25.

Department of Orthopedic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Zhejiang, 310003, Hangzhou, China.

As the most prevalent bone tumor in children and adolescents, the pathogenesis and metastasis of osteosarcoma (OS) remain largely unclear. Here, we investigated the expression and function of a novel circular RNA (circRNA), circROCK1-E3/E4, which is back-spliced from exons 3 and 4 of Rho-associated coiled-coil containing protein kinase 1 (ROCK1) in OS. We found that circROCK1-E3/E4, regulated by the well-known RNA-binding protein quaking (QKI), was downregulated in OS and correlated with unfavorable clinical features of patients with OS. Functional proliferation and cell motility assays indicated that circROCK1-E3/E4 serves as a tumor suppressor in OS cells. Mechanistically, circROCK1-E3/E4 suppressed proliferation and migration by upregulating phosphatase and tensin homolog (PTEN) through microRNA-532-5p (miR-532-5p) sponging. In the constructed nude mouse model, circROCK1-E3/E4 inhibited tumor growth and lung metastasis in vivo. This study demonstrates the functions and molecular mechanisms of circROCK1-E3/E4 in the progression of OS. These findings may identify novel targets for the molecular therapy of OS.
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http://dx.doi.org/10.1038/s12276-022-00806-zDOI Listing
July 2022

Accelerating PERx Reaction Enables Covalent Nanobodies for Potent Neutralization of SARS-Cov-2 and Variants.

Chem 2022 Jul 18. Epub 2022 Jul 18.

Department of Pharmaceutical Chemistry and the Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, 94158, USA.

The long-lasting COVID-19 pandemic and increasing SARS-CoV-2 variants demand effective drugs for prophylactics and treatment. Protein-based biologics offer high specificity yet their noncovalent interactions often lead to drug dissociation and incomplete inhibition. Here we developed covalent nanobodies capable of binding with SARS-CoV-2 irreversibly via proximity-enabled reactive therapeutic (PERx) mechanism. A latent bioreactive amino acid FFY was designed and genetically encoded into nanobodies to accelerate PERx reaction rate. In comparison with the noncovalent wildtype nanobody, the FFY-incorporated covalent nanobodies neutralized both wildtype SARS-CoV-2 and its Alpha, Delta, Epsilon, Lambda, and Omicron variants with potency drastically increased. This PERx-enabled covalent nanobody strategy and insights on potency increase can be valuable to developing effective therapeutics for various viral infections.
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http://dx.doi.org/10.1016/j.chempr.2022.07.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9288967PMC
July 2022

Physical activity attenuated the association of ambient ozone with type 2 diabetes mellitus and fasting blood glucose among rural Chinese population.

Environ Sci Pollut Res Int 2022 Jul 22. Epub 2022 Jul 22.

Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China.

The association of ozone with type 2 diabetes mellitus (T2DM) is uncertain. Moreover, the moderating effect of physical activity on this association is largely unknown. This study aims to evaluate the independent and combined effects of ozone and physical activity on T2DM and fasting blood glucose (FBG) in a Chinese rural adult population. A total of 39,192 participants were enrolled in the Henan Rural Cohort Study. Individual ozone exposure was assessed by using a satellite-based random forest model. The logistic regression and generalized linear models were used to evaluate the associations of ozone and physical activity with T2DM and FBG, respectively. Interaction plots were used to visualize the interaction effects of ozone and physical activity on T2DM or FBG. An interquartile range (IQR) increase in ozone exposure concentration was related to a 53.3% (odds ratio (OR),1.533; 95% confidence interval (CI), 1.426, 1.648) increase in odds of T2DM and a 0.292 mmol/L (95%CI, 0.263, 0.321) higher FBG level, respectively. The effects of ozone on T2DM and FBG generally decreased as physical activity levels increased. Negative additive interactions between ozone and physical activity on T2DM risk were observed (relative excess risk due to interaction (RERI), -0.261; 95%CI, -0.473, -0.048; attributable proportion due to interaction (AP), -0.203; 95%CI, -0.380, -0.027; synergy index (S), 0.520; 95%CI, 0.299, 0.904). The larger effects of ozone were observed among elderly and men on T2DM and FBG than young and women. Long-term exposure to ozone was associated with higher odds of T2DM and higher FBG levels, and these associations might be attenuated by increasing physical activity levels. In addition, there was a negative additive interaction (antagonistic effect) between ozone exposure and physical activity level on T2DM risk, suggesting that physical activity might be an effective method to reduce the burden of T2DM attributed to ozone exposure. Trail registration: The Henan Rural Cohort Study has been registered at Chinese Clinical Trial Register (registration number: ChiCTR-OOC-15006699). Date of registration: 06 July 2015, http://www.chictr.org.cn/showproj.aspx?proj=11375.
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http://dx.doi.org/10.1007/s11356-022-22076-yDOI Listing
July 2022

Phenotypic and genetic analyses of four cases of coagulation factor XII deficiency.

Hematology 2022 Dec;27(1):802-808

Department of Laboratory Medicine, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China.

Objectives: To identify the clinical phenotypic and molecular pathogeneses of four cases of coagulation factor XII deficiency and to deepen the cognition of this disease.

Methods: Coagulation tests were performed through one stage of coagulation on a STAGO coagulation analyser. Coagulation factor XII antigen was detected using enzyme-linked immunosorbent assay. The species conservatism and structural change of mutant proteins were analysed using MegAlign and PYMOL. Meanwhile, missense variants and a novel splice site variant were identified using PolyPhen2 and NetGene2.

Results: The four cases had an observably prolonged activated partial thromboplastin time but without obvious bleeding tendency. Their coagulation factor XII activity (FⅫ:C) and antigen (FXII:Ag) were greatly reduced. Six mutations were detected: NM_000505.4:c.398-1G>A, NP_000496.2:p.(Pro182Leu), NP_000496.2:p.(Ser479Ter), NP_000496.2:p.(Cys559Arg), NC_000005.10:g.7217_7221delinsGTCTA and NM_000505.4:c.1681-1G>A. The first five are newly discovered mutations. The two missense mutation sites were highly conservative, and their protein secondary structure changes may occur not only on the mutation sites but also on other domains. In silico analysis revealed that NP_000496.2:p.(Pro182Leu) may be BENIGN, NP_000496.2:p.(Cys559Arg) may be damaging, and that NM_000505.4:c.398-1G>A and NM_000505.4:c.1681-1G>A are crucial for splicing.

Conclusion: We found six types of mutations, of which five were novel. The two missense mutation sites might be closely related to the function of coagulation factor XII. The mutations were the primary culprits of factor XII deficiency.
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http://dx.doi.org/10.1080/16078454.2022.2083482DOI Listing
December 2022

m6A Topological Transition Coupled to Developmental Regulation of Gene Expression During Mammalian Tissue Development.

Front Cell Dev Biol 2022 5;10:916423. Epub 2022 Jul 5.

School of Medicine, Shenzhen Campus of Sun Yat-sen University, Shenzhen, China.

N6-methyladenosine (m6A) is the most prevalent internal modification and reversible epitranscriptomic mark in messenger RNAs (mRNAs) and plays essential roles in a variety of biological processes. However, the dynamic distribution patterns of m6A and their significance during mammalian tissue development are poorly understood. Here, we found that based on m6A distribution patterns, protein-coding genes were classified into five groups with significantly distinct biological features and functions. Strikingly, comparison of the m6A methylomes of multiple mammalian tissues between fetal and adult stages revealed dynamic m6A topological transition during mammalian tissue development, and identified large numbers of genes with significant m6A loss in 5'UTRs or m6A gain around stop codons. The genes with m6A loss in 5'UTRs were highly enriched in developmental stage-specific genes, and their m6A topological transitions were strongly associated with gene expression regulation during tissue development. The genes with m6A gain around the stop codons were associated with tissue-specific functions. Our findings revealed the existence of different m6A topologies among protein-coding genes that were associated with distinct characteristics. More importantly, these genes with m6A topological transitions were crucial for tissue development regulation of gene expression, suggesting the importance of dynamic m6A topological transitions during mammalian tissue development.
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http://dx.doi.org/10.3389/fcell.2022.916423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9294180PMC
July 2022

Long-term exposure to outdoor light at night and mild cognitive impairment: A nationwide study in Chinese veterans.

Sci Total Environ 2022 Jul 19;847:157441. Epub 2022 Jul 19.

Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.

Background: Evidence is limited for the association between outdoor light at night (LAN) and mild cognitive impairment (MCI), a transitional stage between normal aging and dementia and Alzheimer's disease in the elderly. In this study, the association between outdoor LAN and MCI was examined based on a multi-city study among veterans in China.

Methods: A total of 5496 participants from 18 cities across China were investigated during 2009-2011, selected using a multi-stage random sampling method. Participants' cognitive function was firstly assessed using the Mini Mental State Examination and the Montreal Cognitive Assessment in the Chinese version, and then was further confirmed by clinical examination. Participants' exposure to outdoor LAN was estimated using the Global Radiance Calibrated Nighttime Lights Product at a spatial resolution of around 1 km. The mixed-effects logistic regression model was used to examine the association between outdoor LAN and MCI.

Results: After controlling for covariates, odds ratio (OR) and 95 % confidence intervals (95%CI) of MCI was 1.44 (95%CI: 1.36, 1.52) associated with per interquartile range (IQR = 21.17 nW/cm/sr) increase in exposure to outdoor LAN during the 3 years before the investigation, and for categorical variable of LAN, the highest OR was observed for the highest against the lowest quartile of LAN with a monotonically increasing trend (p values for trend <0.001). Furthermore, higher ORs were observed for females, veterans who had less educational attainment, and had no regular social activities.

Conclusions: Our study revealed that exposure to excessive outdoor LAN was associated with higher risk of MCI. Effective measures should be taken to reduce LAN exposure, which may help to prevent MCI.
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http://dx.doi.org/10.1016/j.scitotenv.2022.157441DOI Listing
July 2022

Novel Antidepressant-Like Properties of the Iron Chelator Deferiprone in a Mouse Model of Depression.

Neurotherapeutics 2022 Jul 21. Epub 2022 Jul 21.

Melbourne Brain Centre, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia.

Depressed individuals who carry the short allele for the serotonin-transporter-linked promotor region of the gene are more vulnerable to stress and have reduced response to first-line antidepressants such as selective serotonin reuptake inhibitors. Since depression severity has been reported to correlate with brain iron levels, the present study aimed to characterise the potential antidepressant properties of the iron chelator deferiprone. Using the serotonin transporter knock-out (5-HTT KO) mouse model, we assessed the behavioural effects of acute deferiprone on the Porsolt swim test (PST) and novelty-suppressed feeding test (NSFT). Brain and blood iron levels were also measured following acute deferiprone. To determine the relevant brain regions activated by deferiprone, we then measured c-Fos expression and applied network-based analyses. We found that deferiprone reduced immobility time in the PST in 5-HTT KO mice and reduced latency to feed in the NSFT in both genotypes, suggesting potential antidepressant-like effects. There was no effect on brain or blood iron levels following deferiprone treatment, potentially indicating an acute iron-independent mechanism. Deferiprone reversed the increase in c-Fos expression induced by swim stress in 5-HTT KO mice in the lateral amygdala. Functional network analyses suggest that hub regions of activity in mice treated with deferiprone include the caudate putamen and prefrontal cortex. The PST-induced increase in network modularity in wild-type mice was not observed in 5-HTT KO mice. Altogether, our data show that the antidepressant-like effects of deferiprone could be acting via an iron-independent mechanism and that these therapeutic effects are underpinned by changes in neuronal activity in the lateral amygdala.
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http://dx.doi.org/10.1007/s13311-022-01257-0DOI Listing
July 2022

Hedyotis diffusa injection induces ferroptosis via the Bax/Bcl2/VDAC2/3 axis in lung adenocarcinoma.

Phytomedicine 2022 Sep 8;104:154319. Epub 2022 Jul 8.

School of Pharmacy, Bengbu Medical College, Bengbu City 233000, China. Electronic address:

Background: Lung cancer has the highest mortality rate among all cancer types. In combination with multiple chemotherapeutic options, traditional Chinese medicine has proven indispensable for the comprehensive treatment of lung cancer.

Purpose: To investigate the effects of Hedyotis diffusa on lung adenocarcinoma cell lines and a BALB/c nude mouse xenograft model, and determine whether HDI could induce ferroptosis in lung adenocarcinoma cells along with the underlying mechanism.

Methods: The anti-tumor activity of HDI was determined in vitro by cell counting kit-8, clonogenic, and transwell assays. Subsequently, electron microscopy, a lipid reactive oxygen species assay, ferrous ion staining, and a malondialdehyde assay were performed to determine the effect on ferroptosis in lung adenocarcinoma cells. The mechanism was then further investigated using small molecule inhibitors, siRNA, and plasmid overexpression in vitro. Finally, the effects of HDI were assessed in tumor-bearing BALB/c nude mice, and HE staining was performed to observe tissue damage after HDI treatment.

Results: In vitro experiments showed that HDI could inhibit the viability of lung adenocarcinoma cells and induce lung adenocarcinoma cells ferroptosis via mechanisms independent of GPX4 and PUFA-PLS pathways but closely associated with VDAC2/3. HDI regulated VDAC2/3 activity by promoting Bax via inhibiting Bcl2, thereby inducing ferroptosis in lung adenocarcinoma cells. Furthermore, in vivo experiments showed that HDI significantly inhibited the growth of subcutaneous tumors in BALB/c nude mice with less organ damage and toxicity, and significantly increased the expression of the ferroptosis-related indicators 4HNE, TFR, and HMOX1 in tumor tissue.

Conclusion: HDI can significantly reduce the survival of lung adenocarcinoma cells in vitro, inhibit the growth of subcutaneously transplanted tumors in BALB/c nude mice in vivo, and induce ferroptosis in lung adenocarcinoma cells via Bcl2 inhibition to promote Bax regulation of VDAC2/3.
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http://dx.doi.org/10.1016/j.phymed.2022.154319DOI Listing
September 2022

Electrochemical biosensor based on topological insulator BiSe tape electrode for HIV-1 DNA detection.

Mikrochim Acta 2022 07 19;189(8):285. Epub 2022 Jul 19.

Centre for Quantum Physics, Key Laboratory of Advanced Optoelectronic Quantum Architecture and Measurement (MOE), School of Physics, Beijing Institute of Technology, Beijing, 100081, China.

A large-size BiSe tape electrode (BTE) was prepared by peeling off a 2 × 1 × 0.5 cm high-quality single crystal. The feasibility of using the flexible BTE as an efficient bioplatform to load Au nanoparticles and probe DNA for HIV-1 DNA electrochemical sensing was explored. Differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS) show that the resultant biosensor has a wide linear range from 0.1 fM to 1 pM, a low detection limit of 50 aM, excellent selectivity, reproducibility and stability, and is superior to the pM DNA detection level of Pt-Au, graphene-AuNPs hybrid biosensors. This outstanding performance is attributed to the intrinsic surface state of BiSe topological insulator in facilitating electron transfer. Therefore, BTE electrochemical biosensor platform has great potential in the application for sensitive detection of DNA biomarkers.
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http://dx.doi.org/10.1007/s00604-022-05365-8DOI Listing
July 2022

Immunomodulatory effects of fentanyl and morphine on DSS- and TNBS-induced colitis.

Immunopharmacol Immunotoxicol 2022 Jul 25:1-14. Epub 2022 Jul 25.

Department of Gastroenterology, The Seventh Medical Center of PLA General Hospital, Beijing, China.

Background: Opioid prescription for inflammatory bowel disease (IBD)-related pain is on the rise. However, the use of strong opioids can result in severe complications, and even death, in IBD patients. This study aimed to define the role of fentanyl and morphine, two representative strong opioids, in the pathogenesis of dextran sodium sulfate (DSS)- and 2,4,6-trinitrobenzenesulfonic acid solution (TNBS)-induced colitis.

Method: DSS and TNBS models were induced in C57BL/6J and Balb/c mice, respectively. Disease activity index (DAI), histopathology, enzyme-linked immunosorbent assay (ELISA), multiplex ELISA, and flow cytometry were performed to evaluate the effects of fentanyl and morphine.

Result: Fentanyl exacerbated DSS- and TNBS-induced colitis, while morphine exhibited no significant immunomodulatory effect. Fentanyl and morphine had no obvious effects on the serum levels of adrenocorticotropic hormone (ACTH), glucocorticoid (GC), and prostaglandin E2 (PGE-2) in DSS and TNBS models. Fentanyl elevated the proportions of Th1 cells, μ-opioid receptor (MOR) + Th1 cells, and MOR + macrophages in the colonic mucosa of DSS-treated mice, and enhanced the proportions of Th1 cells, macrophages, MOR + Th1 cells, and MOR + macrophages in the colonic mucosa of TNBS-treated mice. We found that fentanyl upregulated the levels of inflammatory cytokines/chemokines in MOR + macrophages of the colonic lamina propria mononuclear cells (LPMCs) from DSS-treated mice, whereas it had no effect on the expression of most inflammatory cytokines/chemokines in MOR + macrophages in the colonic LPMCs from TNBS-treated mice.

Conclusion: Our findings suggest that fentanyl exacerbates murine colitis Th1 cell- and macrophage-mediated mechanisms, while morphine exhibits no significant immunomodulatory effect.
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http://dx.doi.org/10.1080/08923973.2022.2102993DOI Listing
July 2022

The inhibition mechanism of polyphenols from Phyllanthus emblica Linn. fruit on acetylcholinesterase: A interaction, kinetic, spectroscopic, and molecular simulation study.

Food Res Int 2022 Aug 10;158:111497. Epub 2022 Jun 10.

College of Food Science, Sichuan Agricultural University, private bag 625014, Yaan, Sichuan, China. Electronic address:

The present study aimed to investigate the inhibition mechanism of polyphenols from Phyllanthus emblica Linn. fruit (PEF, family Euphorbiaceous) on acetylcholinesterase (AChE). Interaction assay, enzyme kinetics, spectroscopic methods, and molecular simulations were performed. Results showed that myricetin, quercetin, fisetin, and gallic acid were the most active components in PEF, because of their low docking scores and strong inhibition ability on AChE with IC values of 0.1974 ± 0.0047, 0.2589 ± 0.0131, 1.0905 ± 0.0598 and 1.503 ± 0.0728 mM, respectively. Among them, the results of kinetic study showed that myricetin, quercetin, and fisetin reversibly inhibited AChE in a competitive manner, while gallic acid inhibited it through a noncompetition type. The interaction assay implied that a combination of the four polyphenols at the selected concentrations manifested a synergistic inhibition effect on AChE in a mixed inhibition type. Fluorescence and UV-vis spectrophotometry revealed that the active PEF polyphenols could strongly quench the intrinsic fluorescence of AChE via a static quenching mechanism. Circular dichroism spectroscopy analysis indicated that the active PEF polyphenols gave rise to the secondary structure changes of AChE by increasing the content of α-helix and reducing β-sheet and random coil conformation. The molecular dynamics simulation results validated that all the four docked polyphenol-AChE complexes were relatively stable according to their root-mean-square distance, root-mean-square fluctuations, solvent accessible surface area, radius of gyration values and hydrogen bonds evaluations during the whole simulation process. Overall, our study provides a creative insight into the further utilization of PEF polyphenols as functional components in exploring natural AChE inhibitors.
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http://dx.doi.org/10.1016/j.foodres.2022.111497DOI Listing
August 2022

Inhibition of mPGES-2 ameliorates NASH by activating NR1D1 via heme.

Hepatology 2022 Jul 15. Epub 2022 Jul 15.

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, P. R. China.

Background And Aims: Nonalcoholic fatty liver disease (NAFLD), a complex metabolic syndrome, has limited therapeutic options. Microsomal prostaglandin E synthase-2 (mPGES-2) was originally discovered as a prostaglandin E (PGE ) synthase; however, it does not produce PGE in the liver. Moreover, the role of mPGES-2 in NAFLD remains undefined. Herein, we aimed to determine the function and mechanism of mPGES-2 in liver steatosis and steatohepatitis.

Approach And Results: To evaluate the role of mPGES-2 in NAFLD, whole-body or hepatocyte-specific mPGES-2-deficient mice fed a high-fat or methionine-choline-deficient diet were used. Compared with control mice, mPGES-2-deficient mice showed reduced hepatic lipid accumulation, along with ameliorated liver injury, inflammation, and fibrosis. Furthermore, the protective effect of mPGES-2 deficiency against NAFLD was dependent on decreased cytochrome P450 4A14 and increased acyl-CoA thioesterase 4 levels regulated by the heme receptor nuclear receptor subfamily 1 group D member 1 (NR1D1), but not PGE . Heme regulated the increased NR1D1 activity mediated by mPGES-2 deficiency. Further, we confirmed the protective role of the mPGES-2 inhibitor SZ0232 in NAFLD therapy.

Conclusion: Our study indicates the pathogenic role of mPGES-2 and outlines the mechanism in mediating NAFLD, thereby highlighting the therapeutic potential of mPGES-2 inhibition in liver steatosis and steatohepatitis.
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http://dx.doi.org/10.1002/hep.32671DOI Listing
July 2022

Amphibian-derived peptide homodimer OA-GL17d promotes skin wound regeneration through the miR-663a/TGF-β1/Smad axis.

Burns Trauma 2022 12;10:tkac032. Epub 2022 Jul 12.

Department of Anatomy and Histology & Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming 650500, Yunnan, China.

Background: Amphibian-derived peptides exhibit considerable potential in the discovery and development of new therapeutic interventions for clinically challenging chronic skin wounds. MicroRNAs (miRNAs) are also considered promising targets for the development of effective therapies against skin wounds. However, further research in this field is anticipated. This study aims to identify and provide a new peptide drug candidate, as well as to explore the underlying miRNA mechanisms and possible miRNA drug target for skin wound healing.

Methods: A combination of Edman degradation, mass spectrometry and cDNA cloning were adopted to determine the amino acid sequence of a peptide that was fractionated from the secretion of frog skin using gel-filtration and reversed-phase high-performance liquid chromatography. The toxicity of the peptide was evaluated by Calcein-AM/propidium iodide (PI) double staining against human keratinocytes (HaCaT cells), hemolytic activity against mice blood cells and acute toxicity against mice. The stability of the peptide in plasma was also evaluated. The prohealing potency of the peptide was determined by MTS, scratch healing and a Transwell experiment against HaCaT cells, full-thickness injury wounds and scald wounds in the dorsal skin of mice. miRNA transcriptome sequencing analysis, enzyme-linked immunosorbent assay, real-time polymerase chain reaction and western blotting were performed to explore the molecular mechanisms.

Results: A novel peptide homodimer (named OA-GL17d) that contains a disulfide bond between the 16th cysteine residue of the peptide monomer and the sequence 'GLFKWHPRCGEEQSMWT' was identified. Analysis showed that OA-GL17d exhibited no hemolytic activity or acute toxicity, but effectively promoted keratinocyte proliferation and migration and strongly stimulated the repair of full-thickness injury wounds and scald wounds in the dorsal skin of mice. Mechanistically, OA-GL17d decreased the level of miR-663a to increase the level of transforming growth factor-β1 (TGF-β1) and activate the subsequent TGF-β1/Smad signaling pathway, thereby resulting in accelerated skin wound re-epithelialization and granular tissue formation.

Conclusions: Our results suggest that OA-GL17d is a new peptide drug candidate for skin wound repair. This study emphasizes the importance of exogenous peptides as molecular probes for exploring competing endogenous RNA mechanisms and indicates that miR-663a may be an effective target for promoting skin repair.
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http://dx.doi.org/10.1093/burnst/tkac032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9273405PMC
July 2022

Erratum: Microenvironment Activatable Nanoprodrug Based on Gripper-like Cyclic Phenylboronic Acid to Precisely and Effectively Alleviate Drug-induced Hepatitis: Erratum.

Theranostics 2022 28;12(10):4603. Epub 2022 May 28.

Personalized Drug Therapy Key Laboratory of Sichuan Province, Department of Pharmacy, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China.

[This corrects the article DOI: 10.7150/thno.61214.].
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http://dx.doi.org/10.7150/thno.74167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9254252PMC
May 2022

Clinical and biochemical characteristics of 12 Chinese primary hypertrophic osteoarthropathy patients with HPGD mutations.

Int J Biol Sci 2022 6;18(9):3908-3917. Epub 2022 Jun 6.

Shanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Primary hypertrophic osteoarthropathy (PHO) is a rare genetic disease mainly affecting the skeletal and skin. Two genes involved in prostaglandin degradation are known to be responsible for PHO: HPGD and SLCO2A1. HPGD gene mutation can cause PHO autosomal recessive 1 (PHOAR1). The purpose of the present study is to analyze the clinical and biochemical characteristics and HPGD gene mutations of 12 Chinese PHOAR1 patients. Twelve PHOAR1 patients from eleven families, including eleven males and one female, were enrolled in this study. Digital clubbing and periostosis came out to be the most common features, which always occur in the early childhood. We performed HPGD gene analysis and identified six novel (c.1A>G, c.34G>T, c.317T>A, c.475G>T, c.548C>T and c.421+1G>T) and one known (c.310_311delCT) HPGD mutations. The recurrent mutation c.310_311delCT were found in all eleven patients, suggesting it is a hotspot mutation. PHOAR1 patients are considered to have an autosomal recessive inheritance pattern. Here, in addition to nine compound heterozygous patients and two homozygous patients, we found one heterozygous patient and reviewed two heterozygous patients reported in other studies. In terms of biochemical characteristics, our PHOAR1 patients have elevated urinary prostaglandin E2 (PGE2) levels (P<0.001) and decreased urinary prostaglandin E metabolite (PGE-M) levels (P=0.04) compared with healthy controls. The patients' PGE2/PGE-M (E/M) ratio came out to be lower than normal subjects (P<0.001). This study provides a comprehensive description of the clinical phenotypes of Chinese PHOAR1 patients and expands the genotypic spectrum of the disease.
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http://dx.doi.org/10.7150/ijbs.71261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9254467PMC
July 2022

Lower Blood Lipid Level Is Associated with the Occurrence of Parkinson's Disease: A Meta-Analysis and Systematic Review.

Int J Clin Pract 2022 9;2022:9773038. Epub 2022 Jun 9.

Emergency Department, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, China.

Background: The changes of blood lipid levels in patients with Parkinson's disease (PD) and its clinical relevance remain unclear. We aimed to evaluate the potential association of blood lipid and the occurrence of PD, to provide evidence to the clinical treatment and nursing care of PD.

Methods: We searched PubMed, Medline, Web of Science, Cochrane Library, Wanfang Database, Weipu Database, and China National Knowledge Infrastructure for studies related to the blood lipid levels and PD until November 30, 2021. Two researchers independently screened the literature and extricated the data including the levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of included studies. RevMan5.3 and Stata 12.0 software were used for statistical processing and analysis.

Results: A total of 15 cohort studies with 9740 participants involving 2032 PD patients and 7708 controls were included. Meta-analysis indicated that TC (SMD = -0.29, 95% CI -0.55∼-0.03, =0.04), TG (SMD = -16.83, 95% CI -20.71∼-12.95, < 0.001), HDL-C (SMD = -0.14, 95% CI -0.26∼-0.02, < 0.001) and LDL-C (SMD = -0.26, 95% CI -0.50∼-0.01, =0.04) level in the PD patients was significantly lower than that of health controls. Sensitivity analysis indicated that the results were stable. No significant publication bias was found between the synthesized outcomes.

Conclusions: Lower blood TC, TG, HDL-C, and LDL-C level are associated with the occurrence of PD. Limited by sample size and study population, further high-quality, large-sample clinical trials in different areas are needed to further determine the relationship between blood lipids and PD in the future.
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http://dx.doi.org/10.1155/2022/9773038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9203242PMC
July 2022

Effect of Electroacupuncture on Insomnia in Patients With Depression: A Randomized Clinical Trial.

JAMA Netw Open 2022 07 1;5(7):e2220563. Epub 2022 Jul 1.

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

Importance: Electroacupuncture (EA) is a widely recognized therapy for depression and sleep disorders in clinical practice, but its efficacy in the treatment of comorbid insomnia and depression remains uncertain.

Objective: To assess the efficacy and safety of EA as an alternative therapy in improving sleep quality and mental state for patients with insomnia and depression.

Design, Setting, And Participants: A 32-week patient- and assessor-blinded, randomized, sham-controlled clinical trial (8-week intervention plus 24-week observational follow-up) was conducted from September 1, 2016, to July 30, 2019, at 3 tertiary hospitals in Shanghai, China. Patients were randomized to receive EA treatment and standard care, sham acupuncture (SA) treatment and standard care, or standard care only as control. Patients were 18 to 70 years of age, had insomnia, and met the criteria for depression as classified in the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). Data were analyzed from May 4 to September 13, 2020.

Interventions: All patients in the 3 groups were provided with standard care guided by psychiatrists. Patients in the EA and SA groups received real or sham acupuncture treatment, 3 sessions per week for 8 weeks, for a total of 24 sessions.

Main Outcomes And Measures: The primary outcome was change in Pittsburgh Sleep Quality Index (PSQI) from baseline to week 8. Secondary outcomes included PSQI at 12, 20, and 32 weeks of follow-up; sleep parameters recorded in actigraphy; Insomnia Severity Index; 17-item Hamilton Depression Rating Scale score; and Self-rating Anxiety Scale score.

Results: Among the 270 patients (194 women [71.9%] and 76 men [28.1%]; mean [SD] age, 50.3 [14.2] years) included in the intention-to-treat analysis, 247 (91.5%) completed all outcome measurements at week 32, and 23 (8.5%) dropped out of the trial. The mean difference in PSQI from baseline to week 8 within the EA group was -6.2 (95% CI, -6.9 to -5.6). At week 8, the difference in PSQI score was -3.6 (95% CI, -4.4 to -2.8; P < .001) between the EA and SA groups and -5.1 (95% CI, -6.0 to -4.2; P < .001) between the EA and control groups. The efficacy of EA in treating insomnia was sustained during the 24-week postintervention follow-up. Significant improvement in the 17-item Hamilton Depression Rating Scale (-10.7 [95% CI, -11.8 to -9.7]), Insomnia Severity Index (-7.6 [95% CI, -8.5 to -6.7]), and Self-rating Anxiety Scale (-2.9 [95% CI, -4.1 to -1.7]) scores and the total sleep time recorded in the actigraphy (29.1 [95% CI, 21.5-36.7] minutes) was observed in the EA group during the 8-week intervention period (P < .001 for all). No between-group differences were found in the frequency of sleep awakenings. No serious adverse events were reported.

Conclusions And Relevance: In this randomized clinical trial of EA treatment for insomnia in patients with depression, quality of sleep improved significantly in the EA group compared with the SA or control group at week 8 and was sustained at week 32.

Trial Registration: ClinicalTrials.gov Identifier: NCT03122080.
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http://dx.doi.org/10.1001/jamanetworkopen.2022.20563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9264041PMC
July 2022

Peripheral Blood Inflammatory Markers Can Predict Benign and Malignant Thyroid Nodules.

Int J Endocrinol 2022 26;2022:2319660. Epub 2022 Jun 26.

Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang University, Jiangxi Clinical Research Center for Endocrine and Metabolic Disease, Nanchang 330006, China.

Objective: Inflammation is related to the occurrence and development of various cancers. This study was designed to explore the role of peripheral blood platelet count, neutrophil-lymphocyte ratio (NLR), platelet count-lymphocyte count ratio (PLR), systemic inflammation index (SII), and other inflammatory markers in predicting benign and malignant Thyroid Imaging Reporting and Data System (TI-RADS) grade 3 thyroid nodules.

Methods: In this retrospective study, 514 patients with TI-RADS grade 3 thyroid nodules were enrolled. According to the pathological results, the patients were divided into the benign and malignant nodule groups. We compared the clinical characteristics between the two groups and analysed the influencing factors for malignant thyroid nodules by univariate and stepwise multivariate logistic regression analyses and then analysed the cutoff value of each influencing factor according to the receiver operating characteristic curve.

Results: The leukocyte count, neutrophil count, platelet count, NLR, PLR, and SII of the malignant nodule group were significantly higher than those of the benign nodule group ( < 0.05), the age and the diameter of nodule of the malignant nodule group were significantly smaller than those of the benign nodule group ( < 0.05). After excluding the influence of confounding factors, SII (odds ratio (OR) = 1.006; 95% confidence interval (CI) = 1.003-1.008; < 0.001), PLR (odds ratio (OR) = 0.981; 95% confidence interval (CI) = 0.981-0.992; < 0.05), leukocyte count (odds ratio (OR) = 0.654; 95% confidence interval (CI) = 0.466-0.892; < 0.05), and age (OR = 0.969; 95% CI = 0.954-0.985; < 0.001) were independent risk factors for malignant thyroid nodules, and the cutoff value of SII and PLR in predicting benign and malignant thyroid nodules were 545.63 × 10/L and 138.63.

Conclusion: This study showed that peripheral blood SII, PLR, leukocyte count and age were independent risk factors for malignant thyroid nodules, and the combination of these can better predict benign and malignant thyroid nodules, which can further guide the diagnosis and treatment of TI-RADS grade 3 thyroid nodules.
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http://dx.doi.org/10.1155/2022/2319660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9251144PMC
June 2022

Bacteriophage protein PEIP is a potent Bacillus subtilis enolase inhibitor.

Cell Rep 2022 Jul;40(1):111026

BioBank, The First Affiliated Hospital of Xi'an Jiaotong University, Shaanxi 710061, China; Institute for Protein Science and Phage Research, The First Affiliated Hospital of Xi'an Jiaotong University, Shaanxi 710061, China; Department of Laboratory Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China. Electronic address:

Enolase is a highly conserved enzyme that presents in all organisms capable of glycolysis or fermentation. Its immediate product phosphoenolpyruvate is essential for other important processes like peptidoglycan synthesis and the phosphotransferase system in bacteria. Therefore, enolase inhibitors are of great interest. Here, we report that Gp60, a phage-encoded enolase inhibitor protein (PEIP) of bacteriophage SPO1 for Bacillus subtilis, is an enolase inhibitor. PEIP-expressing bacteria exhibit growth attenuation, thinner cell walls, and safranin color in Gram staining owing to impaired peptidoglycan synthesis. We solve the structure of PEIP-enolase tetramer and show that PEIP disassembles enolase by disrupting the basic dimer unit. The structure reveals that PEIP does not compete for substrate binding but induces a cascade of conformational changes that limit accessibility to the enolase catalytic site. This phage-inspired disassembly of enolase represents an alternative strategy for the development of anti-microbial drugs.
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http://dx.doi.org/10.1016/j.celrep.2022.111026DOI Listing
July 2022

Autophagy and its mediated mitochondrial quality control maintain pollen tube growth and male fertility in Arabidopsis.

Autophagy 2022 Jul 11:1-16. Epub 2022 Jul 11.

Department of Cell and Developmental Biology, College of Life Sciences, South China Agricultural University, Guangzhou, Hong Kong, China.

Macroautophagy/autophagy, a major catabolic pathway in eukaryotes, participates in plant sexual reproduction including the processes of male gametogenesis and the self-incompatibility response. Rapid pollen tube growth is another essential reproductive process that is metabolically highly demanding to drive the vigorous cell growth for delivery of male gametes for fertilization in angiosperms. Whether and how autophagy operates to maintain the homeostasis of pollen tubes remains unknown. Here, we provide evidence that autophagy is elevated in growing pollen tubes and critically required during pollen tube growth and male fertility in Arabidopsis. We demonstrate that SH3P2, a critical non-ATG regulator of plant autophagy, colocalizes with representative ATG proteins during autophagosome biogenesis in growing pollen tubes. Downregulation of expression significantly disrupts Arabidopsis pollen germination and pollen tube growth. Further analysis of organelle dynamics reveals crosstalk between autophagosomes and prevacuolar compartments following the inhibition of phosphatidylinositol 3-kinase. In addition, time-lapse imaging and tracking of ATG8e-labeled autophagosomes and depolarized mitochondria demonstrate that they interact specifically the ATG8-family interacting motif (AIM)-docking site to mediate mitophagy. Ultrastructural identification of mitophagosomes and two additional forms of autophagosomes imply that multiple types of autophagy are likely to function simultaneously within pollen tubes. Altogether, our results suggest that autophagy is functionally crucial for mediating mitochondrial quality control and canonical cytoplasm recycling during pollen tube growth. AIM: ATG8-family interacting motif; ATG8: autophagy related 8; ATG5: autophagy related 5; ATG7: autophagy related 7; BTH: acibenzolar-S-methyl; DEX: dexamethasone; DNP: 2,4-dinitrophenol; GFP: green fluorescent protein; YFP: yellow fluorescent protein; PtdIns3K: phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate; PVC: prevacuolar compartment; SH3P2: SH3 domain-containing protein 2.
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http://dx.doi.org/10.1080/15548627.2022.2095838DOI Listing
July 2022
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