Publications by authors named "Shuai Shao"

329 Publications

Mercury-induced cutaneous poisoning with generalised erythema and pruritic blister.

Indian J Dermatol Venereol Leprol 2022 Jul 28:1-3. Epub 2022 Jul 28.

Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Shaanxi, China.

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http://dx.doi.org/10.25259/IJDVL_343-2021DOI Listing
July 2022

Optimization of target biochar for the adsorption of target heavy metal ion.

Sci Rep 2022 Aug 11;12(1):13662. Epub 2022 Aug 11.

School of Architecture and Civil Engineering, Anhui Polytechnic University, 8 Middle Beijing Road, Wuhu, 241000, Anhui, People's Republic of China.

The purpose of this work is to study the pyrolysis conditions of target biochar suitable for target heavy metal ion, to characterize the optimized target biochar, and to study the adsorption performance of biochar. With Cu and Zn as the target pollutants, the pyrolysis conditions involved in the preparation process as pyrolysis temperature, pyrolysis time, and heating rate were evaluated and optimized from Box-Behnken Design (BBD), response surface methodology (RSM) and desirability function, the optimized pyrolysis conditions of target biochar for Cu (Cu-BC) and Zn (Zn-BC) were obtained. The optimum pyrolysis parameters for Cu-BC and Zn-BC were pyrolysis time of 3.09 and 2.19 h, pyrolysis temperature of 425.27 and 421.97 °C, and heating rate of 19.65 and 15.88 °C/min. The pseudo-second-order kinetic and Langmuir isotherm model proved to be the best fit for the equilibrium data, with a maximum adsorption capacity (Q) fitted by Langmuir model were 210.56 mg/g for Cu by Cu-BC and 223.32 mg/g for Zn by Zn-BC, which were both higher than the Q of unoptimized biochar (BC) for Cu (177.66 mg/g) and Zn (146.14 mg/g). The physical properties, chemical structure, surface chemistry properties of Cu-BC and Zn-BC were characterized by Zeta potential meter, Scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX), Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). This study puts forward a new perspective for optimizing target biochar production for special environmental application.
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http://dx.doi.org/10.1038/s41598-022-17901-wDOI Listing
August 2022

Preparation and Characterization of Methyl Jasmonate Microcapsules and Their Preserving Effects on Postharvest Potato Tuber.

Molecules 2022 Jul 24;27(15). Epub 2022 Jul 24.

Grain Storage and Security Engineering Research Center of Education Ministry, College of Food Science and Engineering, Henan University of Technology, Zhengzhou 450001, China.

Potato tubers tend to sprout during long-term storage, resulting in quality deterioration and shortened shelf life. Restrictions on the use of chlorpropham, the major potato sprout suppressant, have led to a need to seek alternative methods. In this study, the effects of methyl jasmonate (MeJA) solutions and MeJA microcapsules on sprouting and other key quality attributes of the potato tuber were investigated. The results showed that the MeJA solution was most effective at 300 μmol L according to TOPSIS analysis. To prepare MeJA microcapsules, the optimal formulation is with 0.04% emulsifier, 2.5% sodium alginate, 0.5% chitosan and 3% CaCl. Compared to 300 μmol L MeJA solution, MeJA microcapsules consumed a lower dose of MeJA but demonstrated a better retaining effect on the overall quality attributes of potato tubers. MeJA microcapsules are promising agents for the preservation of postharvest potato tubers.
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http://dx.doi.org/10.3390/molecules27154728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330717PMC
July 2022

Deep Learning-Based Non-Intrusive Commercial Load Monitoring.

Sensors (Basel) 2022 Jul 13;22(14). Epub 2022 Jul 13.

School of Electrical and Information Engineering, Anhui University of Science and Technology, Huainan 232001, China.

Commercial load is an essential demand-side resource. Monitoring commercial loads helps not only commercial customers understand their energy usage to improve energy efficiency but also helps electric utilities develop demand-side management strategies to ensure stable operation of the power system. However, existing non-intrusive methods cannot monitor multiple commercial loads simultaneously and do not consider the high correlation and severe imbalance among commercial loads. Therefore, this paper proposes a deep learning-based non-intrusive commercial load monitoring method to solve these problems. The method takes the total power signal of the commercial building as input and directly determines the state and power consumption of several specific appliances. The key elements of the method are a new neural network structure called TTRNet and a new loss function called MLFL. TTRNet is a multi-label classification model that can autonomously learn correlation information through its unique network structure. MLFL is a loss function specifically designed for multi-label classification tasks, which solves the imbalance problem and improves the monitoring accuracy for challenging loads. To validate the proposed method, experiments are performed separately in seen and unseen scenarios using a public dataset. In the seen scenario, the method achieves an average F1 score of 0.957, which is 7.77% better than existing multi-label classification methods. In the unseen scenario, the average F1 score is 0.904, which is 1.92% better than existing methods. The experimental results show that the method proposed in this paper is both effective and practical.
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http://dx.doi.org/10.3390/s22145250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320136PMC
July 2022

Hypothermia Protects against Ischemic Stroke through Peroxisome-Proliferator-Activated-Receptor Gamma.

Oxid Med Cell Longev 2022 14;2022:6029445. Epub 2022 Jul 14.

Department of Neurosurgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.

Ischemic stroke (IS) remains a global public health burden and requires novel strategies. Hypothermia plays a beneficial role in central nervous system diseases. However, the role of hypothermia in IS has not yet been elucidated. In this study, we determined the role of hypothermia in IS and explored its underlying mechanisms. The IS phenotype was detected based on infarct size, infarct volume, and brain edema in mice. Neuroinflammation was evaluated by the activation of microglial cells and the expression of inflammatory genes after ischemia/reperfusion (I/R) and oxygen-glucose deprivation/reperfusion (OGD/R). Neuronal cell apoptosis, cleaved caspase-3 and Bax/Bcl-2 expressions, cell viability, and lactate dehydrogenase (LDH) release were detected after I/R and OGD/R. Blood-brain barrier (BBB) permeability was calculated based on Evans blue extravasation, tight junction protein expression, cell viability, and LDH release after I/R and OGD/R. The expression of peroxisome proliferator-activated receptor gamma (PPAR) was assessed after OGD/R. Our results suggested that hypothermia significantly reduced infarct size, brain edema, and neuroinflammation after I/R. Hypothermia increased PPAR expression in microglial cells after OGD/R. Mechanistic studies revealed that hypothermia was a protectant against IS, including attenuated apoptosis of neuronal cells and BBB disruption after I/R and OGD/R, by upregulating PPAR expression. The hypothermic effect was reversed by GW9662, a PPAR inhibitor. Our data showed that hypothermia may reduce microglial cell-mediated neuroinflammation by upregulating PPAR expression in microglial cells. Targeting hypothermia may be a feasible approach for IS treatment.
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http://dx.doi.org/10.1155/2022/6029445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303492PMC
July 2022

Therapeutic efficacies of two newly isolated Edwardsiella phages against Edwardsiella piscicida infection.

Microbiol Res 2022 Oct 30;263:127043. Epub 2022 Apr 30.

State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China; Shanghai Engineering Research Center of Maricultured Animal Vaccines, Shanghai 200237, China. Electronic address:

The spread of multi-drug resistant (MDR) bacteria has posed a threat to the development of aquaculture. Due to its effective bactericidal ability, phage therapy has been considered as an alternative to antibiotics to reduce infection caused by MDR bacteria. In this study, two Edwardsiella piscicida phages were newly-isolated and characterized to prevent or treat infection in aquaculture. The phages were designated as vB_EpM_ZHS and vB_EpP_ZHX belonging to Myoviridae and Podoviridae families, respectively, in terms of genome sequence and morphology analyses. The combination of vB_EpM_ZHS and vB_EpP_ZHX improved the therapeutic efficacy both in vitro and in vivo. The phage cocktail significantly inhibited bacterial growth in vitro and decreased approximately 40% of mortality rate and an order of magnitude of bacterial burden in zebrafish and turbot infected by E. piscicida. Moreover, the phage cocktail increased transcription levels of tumor necrosis factor-alpha (TNF-α), interleukin-12 (IL-12), interleukin-6 (IL-6), and interleukin-1β (IL-1β) and alleviated inflammatory levels in the hindgut and spleen of turbots. The results indicate that the phage has a promising potential for therapeutic use against E. piscicida as the antimicrobial alternative to antibiotics in aquaculture.
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http://dx.doi.org/10.1016/j.micres.2022.127043DOI Listing
October 2022

Development and Validation of Nomogram for Predicting Survival of Primary Liver Cancers Using Machine Learning.

Front Oncol 2022 20;12:926359. Epub 2022 Jun 20.

Department of Hepatology and Gastroenterology, Tianjin Union Medical Center, Tianjin Medical University, Tianjin, China.

Background And Aims: Primary liver cancer (PLC) is a common malignancy with poor survival and requires long-term follow-up. Hence, nomograms need to be established to predict overall survival (OS) and cancer-specific survival (CSS) from different databases for patients with PLC.

Methods: Data of PLC patients were downloaded from Surveillance, Epidemiology, and End Results (SEER) and the Cancer Genome Atlas (TCGA) databases. The Kaplan Meier method and log-rank test were used to compare differences in OS and CSS. Independent prognostic factors for patients with PLC were determined by univariate and multivariate Cox regression analyses. Two nomograms were developed based on the result of the multivariable analysis and evaluated by calibration curves and receiver operating characteristic curves.

Results: OS and CSS nomograms were based on age, race, TNM stage, primary diagnosis, and pathologic stage. The area under the curve (AUC) was 0.777, 0.769, and 0.772 for 1-, 3- and 5-year OS. The AUC was 0.739, 0.729 and 0.780 for 1-, 3- and 5-year CSS. The performance of the two new models was then evaluated using calibration curves.

Conclusions: We systematically reviewed the prognosis of PLC and developed two nomograms. Both nomograms facilitate clinical application and may benefit clinical decision-making.
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http://dx.doi.org/10.3389/fonc.2022.926359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9258303PMC
June 2022

Safety and immunogenicity of a hybrid-type vaccine booster in BBIBP-CorV recipients in a randomized phase 2 trial.

Nat Commun 2022 06 27;13(1):3654. Epub 2022 Jun 27.

The Sixth Laboratory, National Vaccine and Serum Institute (NVSI), Beijing, China.

NVSI-06-08 is a potential broad-spectrum recombinant COVID-19 vaccine that integrates the antigens from multiple SARS-CoV-2 strains into a single immunogen. Here, we evaluate the safety and immunogenicity of NVSI-06-08 as a heterologous booster dose in BBIBP-CorV recipients in a randomized, double-blind, controlled, phase 2 trial conducted in the United Arab Emirates (NCT05069129). Three groups of healthy adults over 18 years of age (600 participants per group) who have administered two doses of BBIBP-CorV 4-6-month, 7-9-month and >9-month earlier, respectively, are randomized 1:1 to receive either a homologous booster of BBIBP-CorV or a heterologous booster of NVSI-06-08. The incidence of adverse reactions is low, and the overall safety profile is quite similar between two booster regimens. Both Neutralizing and IgG antibodies elicited by NVSI-06-08 booster are significantly higher than those by BBIBP-CorV booster against not only SARS-CoV-2 prototype strain but also multiple variants of concerns (VOCs). Especially, the neutralizing antibody GMT against Omicron variant induced by heterologous NVSI-06-08 booster reaches 367.67, which is substantially greater than that boosted by BBIBP-CorV (GMT: 45.03). In summary, NVSI-06-08 is safe and immunogenic as a booster dose following two doses of BBIBP-CorV, which is immunogenically superior to the homologous boost with another dose of BBIBP-CorV.
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http://dx.doi.org/10.1038/s41467-022-31379-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9237056PMC
June 2022

The analysis of prognostic factors of primary small intestinal gastrointestinal stromal tumors with R0 resection: A single-center retrospective study.

Medicine (Baltimore) 2022 Jun 24;101(25):e29487. Epub 2022 Jun 24.

Department of Hernia and Colorectal Surgery, The Second Hospital of Dalian Medical University, Dalian, People's Republic of China.

Objective: We aim to assess factors that affect overall survival in patients with primary small intestinal gastrointestinal stromal tumors (GISTs) who had undergone R0 resection.

Method: A retrospective analysis reviewed the data of 82 consecutive confirmed GIST patients at a single medical center in China from January 2012 to June 2020. The survival curve was estimated using the Kaplan-Meier method, and independent prognostic factors were confirmed using the Cox regression model.

Results: A total of 82 patients were included in the study: 42 men and 40 women, the mean age was 59 years old (23-83 years old). Tumors were commonly found in the jejunum (46.3%), ileum (20.7%), and duodenum (32.9%). The median tumor size was 6.0 cm (range: 1.0-15.0 cm). The number of mitoses per one 50 high-power field was used to define the mitotic rates. In our present study, 56 patients presented a mitotic rate ≤5 (68.3%) and 26 patients showed a rate >5 (31.7%) at the time of diagnosis. All patients accepted tumor resection without lymph node resection. The positivity rate was 97.6% for CD117, 96.3% for delay of germination 1, 65.9% for CD34, 6.1% for S-100, and 59.8% for smooth muscle actin using immunohistochemistry. Tumor size, tumor rupture, Ki67 index, mitotic index, and postoperative imatinib were independent prognostic factors for small intestinal GISTs.

Conclusions: In this study, larger tumor size, high Ki67 index, high mitotic index, the occurrence of tumor rupture, and use of imatinib were independent unfavorable prognostic indicators.
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http://dx.doi.org/10.1097/MD.0000000000029487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9276149PMC
June 2022

Immunogenicity and safety of NVSI-06-07 as a heterologous booster after priming with BBIBP-CorV: a phase 2 trial.

Signal Transduct Target Ther 2022 06 6;7(1):172. Epub 2022 Jun 6.

Lanzhou Institute of Biological Products Company Limited, Lanzhou, China.

The increased coronavirus disease 2019 (COVID-19) breakthrough cases pose the need of booster vaccination. We conducted a randomised, double-blinded, controlled, phase 2 trial to assess the immunogenicity and safety of the heterologous prime-boost vaccination with an inactivated COVID-19 vaccine (BBIBP-CorV) followed by a recombinant protein-based vaccine (NVSI-06-07), using homologous boost with BBIBP-CorV as control. Three groups of healthy adults (600 individuals per group) who had completed two-dose BBIBP-CorV vaccinations 1-3 months, 4-6 months and ≥6 months earlier, respectively, were randomly assigned in a 1:1 ratio to receive either NVSI-06-07 or BBIBP-CorV boost. Immunogenicity assays showed that in NVSI-06-07 groups, neutralizing antibody geometric mean titers (GMTs) against the prototype SARS-CoV-2 increased by 21.01-63.85 folds on day 28 after vaccination, whereas only 4.20-16.78 folds of increases were observed in control groups. For Omicron variant, the neutralizing antibody GMT elicited by homologous boost was 37.91 on day 14, however, a significantly higher neutralizing GMT of 292.53 was induced by heterologous booster. Similar results were obtained for other SARS-CoV-2 variants of concerns (VOCs), including Alpha, Beta and Delta. Both heterologous and homologous boosters have a good safety profile. Local and systemic adverse reactions were absent, mild or moderate in most participants, and the overall safety was quite similar between two booster schemes. Our findings indicated that NVSI-06-07 is safe and immunogenic as a heterologous booster in BBIBP-CorV recipients and was immunogenically superior to the homologous booster against not only SARS-CoV-2 prototype strain but also VOCs, including Omicron.
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http://dx.doi.org/10.1038/s41392-022-00984-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9167817PMC
June 2022

Periodontitis Salivary Microbiota Aggravates Ischemic Stroke Through IL-17A.

Front Neurosci 2022 19;16:876582. Epub 2022 May 19.

Department of Neurosurgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Although epidemiological studies suggest that periodontitis is tightly associated with ischemic stroke, its impact on ischemic stroke and the underlysing mechanisms are poorly understood. Recent studies have shown that alteration in gut microbiota composition influences the outcomes of ischemic stroke. In the state of periodontitis, many oral pathogenic bacteria in the saliva are swallowed and transmitted to the gut. However, the role of periodontitis microbiota in the pathogenesis and progression of ischemic stroke is unclear. Therefore, we hypothesized that the periodontitis salivary microbiota influences the gut immune system and aggravates ischemic stroke. Mice receiving gavage of periodontitis salivary microbiota showed significantly worse stroke outcomes. And these mice also manifested more severe neuroinflammation, with higher infiltration of inflammatory cells and expression of inflammatory cytokines in the ischemic brain. More accumulation of Th17 cells and IL-17 γδ T cells were observed in the ileum. And in Kaede transgenic mice after photoconversion. Migration of CD4 T cells and γδ T cells from the ileum to the brain was observed after ischemic stroke in photoconverted Kaede transgenic mice. Furthermore, the worse stroke outcome was abolished in the IL-17A knockout mice. These findings suggest that periodontitis salivary microbiota increased IL-17A-producing immune cells in the gut, likely promoted the migration of these cells from the gut to the brain, and subsequently provoked neuroinflammation after ischemic stroke. These findings have revealed the role of periodontitis in ischemic stroke through the gut and provided new insights into the worse outcome of ischemic stroke coexisting with periodontitis in clinical trials.
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http://dx.doi.org/10.3389/fnins.2022.876582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9160974PMC
May 2022

Healthy eating and all-cause mortality among Chinese aged 80 years or older.

Int J Behav Nutr Phys Act 2022 May 26;19(1):60. Epub 2022 May 26.

Duke Global Health Institute, Duke University, 310 Trent Drive, Durham, NC, 27710, USA.

Background: There is little evidence of the influence of dietary patterns on mortality risk among adults 80 years or older ("oldest-old"). We evaluated the association between the Simplified Healthy Eating index (SHE-index) and mortality among Chinese oldest-old.

Methods: Population-based cohort study from the Chinese Longitudinal Healthy Longevity Survey (CLHLS 1998-2014, n = 35 927), conducted in 22 Chinese provinces, were pooled for analysis. The first seven waves of the CLHLS (1998, 2000, 2002, 2005, 2008-09, 2011-12, and 2013-2014) were utilized, with follow-up to the last wave (2018) (range 0-21 years). The SHE-index was collected in each wave, and was constructed from intake frequency of nine dietary variables, with a higher score indicating better diet quality. Cox proportional hazards model with dietary patterns as a time-varying exposure was employed to analyze the relationship between SHE-index and mortality.

Results: At baseline, the median age of all participants was 92 years (25th percentile, 85 years; 75th percentile, 100 years). In multivariable models, the hazard ratios (95% confidence intervals) for SHE-index quartile 2, quartile 3 and quartile 4 versus quartile1 were 0.91 (0.88, 0.93), 0.89 (0.86, 0.92) and 0.82 (0.78, 0.85), respectively. Results were generally consistent for men and women and in a large number of sensitivity analyses.

Conclusions: Healthier eating patterns were associated with a significant reduction in the risk of all-cause mortality among Chinese oldest-old, lending support to the importance of life-long adherence to healthy diet into advanced old age.
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http://dx.doi.org/10.1186/s12966-022-01280-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9137098PMC
May 2022

How do China's lockdown and post-COVID-19 stimuli impact carbon emissions and economic output? Retrospective estimates and prospective trajectories.

iScience 2022 May 30;25(5):104328. Epub 2022 Apr 30.

School of Economics, Fudan University, Shanghai 200433, China.

This paper develops a multi-sector and multi-factor structural gravity model that allows an analytical and quantitative decomposition of the emission and output changes into composition and technique effects. We find that the negative production shock of China's containment policy propagates globally via supply chains, with the carbon-intensive sectors experiencing the greatest carbon emission shocks. We further reveal that China's current stimulus package in 2021-2025 is consistent with China's emission intensity-reduction goals for 2025, but further efforts are required to meet China's carbon emissions-peaking target in 2030 and Cancun 2°C goal. Short-term changes in carbon emissions resulting from lockdowns and initial fiscal stimuli in "economic rescue" period have minor long-term effects, whereas the transitional direction of future fiscal stimulus exerts more predominant impact on long-term carbon emissions. The efficiency improvement effects are more important than the sectoral structure effects of the fiscal stimulus in achieving greener economic growth.
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http://dx.doi.org/10.1016/j.isci.2022.104328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9118742PMC
May 2022

Angiotensin receptor-neprilysin inhibitor attenuates cardiac hypertrophy and improves diastolic dysfunction in a mouse model of heart failure with preserved ejection fraction.

Clin Exp Pharmacol Physiol 2022 Aug 14;49(8):848-857. Epub 2022 Jun 14.

Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular disease, Department of Cardiology, Tianjin Institute of Cardiology, the Second Hospital of Tianjin Medical University, Tianjin, China.

LCZ696, an angiotensin receptor-neprilysin inhibitor, has shown promising clinical efficacy in patients with heart failure (HF) with reduced ejection fraction. However, its potential effects on heart failure with preserved ejection fraction (HFpEF) are still not fully understood. We evaluated the effect of LCZ696 on HFpEF in transverse aortic constriction mice and compared it with the effect of the angiotensin receptor blocker, valsartan. We found that LCZ696 improved cardiac diastolic function by reducing ventricular hypertrophy and fibrosis in mice with overload-induced diastolic dysfunction. In addition, there was superior inhibition of LCZ696 than stand-alone valsartan. As a potential underlying mechanism, we demonstrated that LCZ696 behaves as a potent suppressor of calcium-mediated calcineurin-nuclear factor of activated T cells (NFAT) signalling transduction pathways. Hence, we demonstrated the protective effects of LCZ696 in overload-induced HFpEF and provided a pharmaceutical therapeutic strategy for related diseases.
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http://dx.doi.org/10.1111/1440-1681.13672DOI Listing
August 2022

Systematic Analysis of E2F Expression and Its Relation in Colorectal Cancer Prognosis.

Int J Gen Med 2022 11;15:4849-4870. Epub 2022 May 11.

Department of Hernia and Colorectal Surgery, The Second Hospital of Dalian Medical University, Dalian, People's Republic of China.

Background: The E2 factor (E2F) family of transcription factors is dysregulated in numerous cancer types and may play a vital role in the development of various malignancies. However, to our knowledge, the specific function of each of the E2Fs and their relation to the disease prognosis of colorectal cancer (CRC) patients remain unknown.

Materials And Methods: We used different publicly available databases and tools, such as ONCOMINE, GEPIA2, UALCAN, cBioPortal, Kaplan-Meier plotter, Metascape, and TIMER analysis, to do an in silico exploration of the potential roles of E2Fs in CRC.

Results: In our analyses, we found a downregulation of E2F2 expression and an upregulation of E2F1 and E2F3-8 expression in CRC tissues compared to normal controls. These findings were consistent with our subgroup analysis using the different clinicopathological features of CRC patients. Furthermore, overexpression of E2F3 and E2F4 were significantly correlated with worse overall survival (OS) in colon cancer patients. Meanwhile, low levels of E2F2 resulted in a shorter OS in rectal cancer patients. The E2F family members had varying degrees of genetic alterations with the highest alteration rate observed in E2F1 (23%). Interestingly, a moderate positive express correlation had been found in the following E2F family members: E2F1 with E2F4, E2F2 with E2F7, E2F2 with E2F8, and E2F7 with E2F8. In addition, spearman analysis revealed that E2Fs have a strong positive correlation with the critical oncogenes in CRC patients. Lastly, the expression of E2Fs was significantly associated with the infiltration of six immune cells.

Conclusion: In this study, we found that E2F2, E2F3, and E2F4 have the potential to be novel prognostic biomarkers in CRC. The role of these E2F family members in disease pathology may be related to their functions in cell cycle regulation, therapeutic resistance, immune cell infiltration, and epithelia-to-mesenchymal transition. Further studies are required to validate our results; however, our findings may help provide a foundation for broadening our understanding of CRC pathology.
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http://dx.doi.org/10.2147/IJGM.S352141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9109810PMC
May 2022

Physico-chemical properties, antioxidant activity, and ACE inhibitory activity of protein hydrolysates from wild jujube seed.

J Food Sci 2022 Jun 3;87(6):2484-2503. Epub 2022 May 3.

Changchun University of Chinese Medicine, Changchun, China.

Wild jujube seed protein (WJSP) as one kind of functional food material has attracted much attention due to its highly nutritive and medicinal value in anti-inflammatory and improving immunomodulatory ability. However, owing to its large molecular weight and complex structure, biological activities of WJSP were greatly limited and cannot be fully utilized by the human body. Therefore, how to improve the bioavailability of WJSP and develop promising WJSP nutritious materials is a great challenge. In this work, wild jujube seed protein hydrolysates (WJSPHs) were prepared from WJSP via enzymatic hydrolysis method, and their physico-chemical properties, antioxidant activity, and angiotensin converting enzyme (ACE) inhibitory activity in vitro have been investigated for the first time. SDS-PAGE electrophoresis and size-exclusion chromatographic results indicate that WJSPHs have lower molecular weight distribution (< 5,000 Da) than WJSP. Circular dichroism (CD) spectroscopy and Fourier transform infrared spectroscopy (FTIR) results illustrated that random coil is the main secondary structure of WJSPHs. Antioxidant experiments indicate that WJSPHs exhibit high radicals-scavenging ability of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals (94.60%), 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulfonate) (ABTS ) radicals (90.84%), superoxide radicals (44.77%), and hydroxyl radicals (47.77%). In vitro, WJSPHs can significantly decrease the accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA), and increase the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in HepG2 cells. Moreover, ACE activity was found that can be significantly inhibited by WJSPHs (73.02%). Therefore, all previously mentioned results suggest that WJSPHs may be a promising antioxidant food to prevent oxidative-related diseases in future. PRACTICAL APPLICATION: This study shows that WJSPHs exhibit high antioxidant activity and ACE inhibitory activity in vitro, which provide potential application value as antioxidant peptides to prevent oxidative-related diseases.
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http://dx.doi.org/10.1111/1750-3841.16157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325541PMC
June 2022

Ketogenic Diet Modulates Neuroinflammation via Metabolites from Lactobacillus reuteri After Repetitive Mild Traumatic Brain Injury in Adolescent Mice.

Cell Mol Neurobiol 2022 Apr 30. Epub 2022 Apr 30.

Department of Neurosurgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, No. 160 Pujian Road, Shanghai, 200127, People's Republic of China.

Repetitive mild traumatic brain injury (rmTBI) is associated with a range of neural changes which is characterized by axonal injury and neuroinflammation. Ketogenic diet (KD) is regarded as a potential therapy for facilitating recovery after moderate-severe traumatic brain injury (TBI). However, its effect on rmTBI has not been fully studied. In this study, we evaluated the anti-neuroinflammation effects of KD after rmTBI in adolescent mice and explored the potential mechanisms. Experimentally, specific pathogen-free (SPF) adolescent male C57BL/6 mice received a sham surgery or repetitive mild controlled cortical impacts consecutively for 7 days. The uninjured mice received the standard diet, and the mice with rmTBI were fed either the standard diet or KD for 7 days. One week later, all mice were subjected to behavioral tests and experimental analysis. Results suggest that KD significantly increased blood beta-hydroxybutyrate (β-HB) levels and improved neurological function. KD also reduced white matter damage, microgliosis, and astrogliosis induced by rmTBI. Aryl hydrocarbon receptor (AHR) signaling pathway, which was mediated by indole-3-acetic acid (3-IAA) from Lactobacillus reuteri (L. reuteri) in gut and activated in microglia and astrocytes after rmTBI, was inhibited by KD. The expression level of the toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88) in inflammatory cells, which mediates the NF-κB pathway, was also attenuated by KD. Taken together, our results indicated that KD can promote recovery following rmTBI in adolescent mice. KD may modulate neuroinflammation by altering L. reuteri in gut and its metabolites. The inhibition of indole/AHR pathway and the downregulation of TLR4/MyD88 may play a role in the beneficial effect of KD against neuroinflammation in rmTBI mice.
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http://dx.doi.org/10.1007/s10571-022-01226-3DOI Listing
April 2022

Activation of the C3a anaphylatoxin receptor inhibits keratinocyte proliferation by regulating keratin 6, keratin 16, and keratin 17 in psoriasis.

FASEB J 2022 05;36(5):e22322

Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Emerging evidence suggests that signaling through the C3a anaphylatoxin receptor (C3aR) protects against various inflammation-related diseases. However, the role of C3aR in psoriasis remains unknown. The purpose of this study was to investigate the possible protective role of C3aR in psoriasis and to explore the underlying molecular mechanisms. We initially found that the psoriatic epidermis exhibited significantly decreased C3aR expression. C3aR showed protective roles in mouse models of imiquimod (IMQ)- and interleukin-23-induced psoriasis. Furthermore, increased epidermal thickness and keratin 6 (K6), K16, and K17 expression occurred in the ears and backs of C3aR mice. Pharmacological treatment with a C3aR agonist ameliorated IMQ-induced psoriasiform lesions in mice and decreased the expression of K6, K16, and K17. Additionally, the signal transducer and activator of transcription 3 (STAT3) pathway participated in the protective function of C3aR. More importantly, the expression levels of K6, K16, and K17 in keratinocytes were all restored in HaCaT cells transfected with a C3aR-overexpression plasmid after treating them with colivelin (a STAT3 activator). Our findings demonstrate that C3aR protects against the development of psoriasis and suggest that C3aR confers protection by negatively regulating K6, K16, and K17 expression in a STAT3-dependent manner, thus inhibiting keratinocyte proliferation and helping reverse the pathogenesis of psoriasis.
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http://dx.doi.org/10.1096/fj.202101458RDOI Listing
May 2022

extract: chemical composition and whitening, antioxidant, and anti-inflammatory effects.

RSC Adv 2021 Mar 15;11(18):10814-10826. Epub 2021 Mar 15.

Jilin Ginseng Academy, Changchun University of Chinese Medicine Changchun Jilin China.

Whitening cosmetics have a large market scale and broad development prospects, while whitening products of traditional Chinese medicine have always been a research hotspot. In this study, the whitening active extract of (PGE) was isolated and purified for the first time, and the whitening activity mechanism and chemical composition of PGE were elucidated. A total of 45 components were identified high-performance liquid chromatography-mass spectrometry (HPLC-MS) analysis, including arbutin, syringin, chlorogenic acid, platycoside E, platycodin D, baicalin, platycodin D, and luteolin. The scavenging rates of PGE toward DPPH and ABTS free radicals were 98.03% and 84.30%, respectively. The inhibition rate of PGE toward tyrosinase was up to 97.71%. The PGE had significant anti-inflammatory effects on RAW264.7 macrophages stimulated by lipopolysaccharide (LPS) and had significant inhibition effects on tyrosinase and melanin generation of B16F10 cells stimulated by α-MSH. The results showed that the PGE achieved a synergistic whitening effect by inhibiting the activation of oxygen free radicals on tyrosinase, antioxidation, anti-inflammatory effect, enzyme activity, and melanin generation. As a whitening agent extracted from natural plants, PGE has great potential in the research and development of plant whitening cosmetics, which lays a foundation for the further development and utilization of resources and also provides a theoretical basis for the development of green and organic whitening cosmetics.
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http://dx.doi.org/10.1039/d0ra09443aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8695864PMC
March 2021

Characterization of the Agrobacterium octopine-cucumopine catabolic plasmid pAtAg67.

Plasmid 2022 05 2;121:102629. Epub 2022 Apr 2.

Institute of Biology, Sylvius Laboratory, Leiden University, 2333BE Leiden, the Netherlands. Electronic address:

In addition to tumor-inducing agrobacteria, non-pathogenic strains are often isolated from crown gall tumors. Such non-pathogenic strains sometimes contain catabolic plasmids that allow them to take advantage of the opines produced in the tumors. Here we characterize for the first time an octopine catabolic plasmid, pAtAg67, which is derived from an Agrobacterium strain isolated from a grapevine tumor in Crete. By sequence analysis, we deduce that pAtAg67 enables its host to catabolize not only octopine, but also cucumopine and agrocinopine-like compounds. We found that a highly similar set of catabolic genes was present in the Ti plasmids of tumorigenic octopine-cucumopine grapevine strains such as pTiAg57. However, the catabolic genes in octopine-cucumopine Ti plasmids were interrupted by a T-DNA segment. As no T-DNA remnants, virulence genes or border repeats were found in pAtAg67, catabolic plasmid pAtAg67 does not appear to be a degenerate octopine-cucumopine Ti plasmid. In line, plasmid pAtAg67 was found to be compatible with incRh1 octopine Ti plasmids, but to be incompatible with the incRh2 agropine Ti plasmid pTiBo542, forming cointegrates by recombination in the homologous trb genes.
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http://dx.doi.org/10.1016/j.plasmid.2022.102629DOI Listing
May 2022

Birds of a Feather Flock Together: Category-Divergence Guidance for Domain Adaptive Segmentation.

IEEE Trans Image Process 2022 8;31:2878-2892. Epub 2022 Apr 8.

Unsupervised domain adaptation (UDA) aims to enhance the generalization capability of a certain model from a source domain to a target domain. Present UDA models focus on alleviating the domain shift by minimizing the feature discrepancy between the source domain and the target domain but usually ignore the class confusion problem. In this work, we propose an Inter-class Separation and Intra-class Aggregation (ISIA) mechanism. It encourages the cross-domain representative consistency between the same categories and differentiation among diverse categories. In this way, the features belonging to the same categories are aligned together and the confusable categories are separated. By measuring the align complexity of each category, we design an Adaptive-weighted Instance Matching (AIM) strategy to further optimize the instance-level adaptation. Based on our proposed methods, we also raise a hierarchical unsupervised domain adaptation framework for cross-domain semantic segmentation task. Through performing the image-level, feature-level, category-level and instance-level alignment, our method achieves a stronger generalization performance of the model from the source domain to the target domain. In two typical cross-domain semantic segmentation tasks, i.e., GTA 5→ Cityscapes and SYNTHIA → Cityscapes, our method achieves the state-of-the-art segmentation accuracy. We also build two cross-domain semantic segmentation datasets based on the publicly available data, i.e., remote sensing building segmentation and road segmentation, for domain adaptive segmentation. Our code, models and datasets are available at https://github.com/HibiscusYB/BAFFT.
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http://dx.doi.org/10.1109/TIP.2022.3162471DOI Listing
April 2022

A Novel Phage Infecting the Marine Photoheterotrophic Bacterium .

Viruses 2022 03 2;14(3). Epub 2022 Mar 2.

State Key Laboratory of Marine Environmental Science, Fujian Key Laboratory of Marine Carbon Sequestration, College of Ocean and Earth Sciences, Xiamen University, Xiamen 361102, China.

This study isolated and characterized a new phage infecting the marine photoheterotrophic bacterium , which fills the gap in research on phages targeting this ecologically important species. The phage vB_CbaS-RXM (RXM) has a dsDNA genome with a length of 104,206 bp and G+C content of 61.64%. The taxonomic analysis found a close evolutionary relationship between RXM, phage vB_EliS-L02, and phage Lacusarx, and we propose that RXM represents a new species of the genus. A one-step growth curve revealed a burst size of 75 plaque-forming units (PFUs) per cell in a 3-hour infection cycle. The lysis profile of RXM showed an intraspecific lethal rate of 26.3% against 38 citromicrobial strains. RXM contains 15 auxiliary metabolic genes (AMGs) related to diverse cellular processes, such as putative metabolic innovation and hijacking of host nucleotide metabolism to enhance its biosynthetic capacity. An in-depth analysis showed that phage functional genes strongly rely on the host for translation, while the translation of unique phage genes with less host dependency may be complemented by phage tRNA. Overall, our study investigated the infection kinetics, genetic traits, taxonomy, and predicted roles of AMGs and tRNA genes of this new phage, which contributes to a better understanding of phage diversity and phage-bacterium interactions.
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http://dx.doi.org/10.3390/v14030512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8953757PMC
March 2022

Xenogeneic nucleoid-associated EnrR thwarts H-NS silencing of bacterial virulence with unique DNA binding.

Nucleic Acids Res 2022 04;50(7):3777-3798

State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.

Type III and type VI secretion systems (T3/T6SS) are encoded in horizontally acquired genomic islands (GIs) that play crucial roles in evolution and virulence in bacterial pathogens. T3/T6SS expression is subjected to tight control by the host xenogeneic silencer H-NS, but how this mechanism is counteracted remains to be illuminated. Here, we report that xenogeneic nucleoid-associated protein EnrR encoded in a GI is essential for virulence in pathogenic bacteria Edwardsiella and Salmonella. We showed that EnrR plays critical roles in T3/T6SS expression in these bacteria. Various biochemical and genetic analyses demonstrated that EnrR binds and derepresses the promoter of esrB, the critical regulator of T3/T6SS, to promote their expression by competing with H-NS. Additionally, EnrR targets AT-rich regions, globally modulates the expression of ∼363 genes and is involved in various cellular processes. Crystal structures of EnrR in complex with a specific AT-rich palindromic DNA revealed a new DNA-binding mode that involves conserved HTH-mediated interactions with the major groove and contacts of its N-terminal extension to the minor groove in the symmetry-related duplex. Collectively, these data demonstrate that EnrR is a virulence activator that can antagonize H-NS, highlighting a unique mechanism by which bacterial xenogeneic regulators recognize and regulate foreign DNA.
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http://dx.doi.org/10.1093/nar/gkac180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023278PMC
April 2022

Osteoblast MR deficiency protects against adverse ventricular remodeling after myocardial infarction.

J Mol Cell Cardiol 2022 06 18;167:40-51. Epub 2022 Mar 18.

Laboratory of Oral Microbiota and Systemic Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai 200011, China. Electronic address:

Rationale: Mineralocorticoid receptor (MR) antagonists have been clinically used to treat heart failure. However, the underlying cellular and molecular mechanisms remain incompletely understood.

Methods And Results: Using osteoblast MR knockout (MR) mouse in combination with myocardial infarction (MI) model, we demonstrated that MR deficiency in osteoblasts significantly improved cardiac function, promoted myocardial healing, as well as attenuated cardiac hypertrophy, fibrosis and inflammatory response after MI. Gene expression profiling using RNA sequencing revealed suppressed expression of osteocalcin (OCN) in calvaria from MR mice compared to littermate control (MR) mice with or without MI. Plasma levels of undercarboxylated OCN (ucOCN) were also markedly decreased in MR mice compared to MR mice. Administration of ucOCN abolished the protective effects of osteoblast MR deficiency on infarcted hearts. Mechanistically, ucOCN treatment promoted proliferation and inflammatory cytokine secretion in macrophages. Spironolactone, an MR antagonist, significantly inhibited the expression and secretion of OCN in post-MI mice. More importantly, spironolactone decreased plasma levels of ucOCN and inflammatory cytokines in heart failure patients.

Conclusions: MR deficiency in osteoblasts alleviates pathological ventricular remodeling after MI, likely through its regulation on OCN. Spironolactone may work through osteoblast MR/OCN axis to exert its therapeutic effects on pathological ventricular remodeling and heart failure in mice and human patients.
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http://dx.doi.org/10.1016/j.yjmcc.2022.03.003DOI Listing
June 2022

Alcohol consumption in relation to the incidence of atrial fibrillation in an elderly Chinese population.

J Geriatr Cardiol 2022 Jan;19(1):52-60

School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Alcohol consumption is a known modifiable risk factor for atrial fibrillation. The association, however, might differ according to gender. We investigated gender-specific associations between alcohol consumption and incident atrial fibrillation in an elderly Chinese population.

Methods: Our study participants were elderly residents (≥ 65 years) recruited from five community health centers in the urban area of Shanghai ( = 6,618). Alcohol intake was classified as never drinkers and current light-to-moderate (< 40 g/day) and heavy drinkers (≥ 40 g/day). Atrial fibrillation was detected by a 30-s single-lead electrocardiography (ECG, AliveCor Heart Monitor) and further evaluated with a regular 12-lead ECG.

Results: During a median of 2.1 years (interquartile range: 2.0-2.2) follow-up, the incidence rate of atrial fibrillation was 1.10% in all study participants. It was slightly but non-significantly higher in men ( = 2849) than women ( = 3769, 1.30% . 0.96%, = 0.19) and in current drinkers ( = 793) than never drinkers ( = 5825, 1.64% . 1.03%, = 0.12). In both unadjusted and adjusted analyses, there was interaction between sex and current alcohol intake in relation to the incidence of atrial fibrillation ( < 0.0001). After adjustment for confounding factors, current drinkers had a significantly higher incidence rate of atrial fibrillation than never drinkers in women (12.96% [7/54] . 0.78% [29/3715], adjusted odds ratio [OR] = 10.25, 95% confidence interval [CI]: 3.54-29.67, < 0.0001), but not in men (0.81% [6/739] . 1.47% [31/2110], OR = 0.62, 95% CI: 0.25-1.51, = 0.29).

Conclusions: Our study showed a significant association between alcohol intake and the incidence of atrial fibrillation in elderly Chinese women, but not men.
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http://dx.doi.org/10.11909/j.issn.1671-5411.2022.01.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8832043PMC
January 2022

Coordinate regulation of carbohydrate metabolism and virulence by PtsH in pathogen Edwardsiella piscicida.

Appl Microbiol Biotechnol 2022 Mar 26;106(5-6):2063-2077. Epub 2022 Feb 26.

State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China.

Carbohydrate metabolism of bacterial pathogens conducts crucial roles in regulating pathogenesis but the molecular mechanisms by which metabolisms and virulence are been modulated and coordinated remain to be illuminated. Here, we investigated in this regard Edwardsiella piscicida, a notorious zoonotic pathogen previously named E. tarda that could ferment very few PTS sugars including glucose, fructose, mannose, N-acetylglucosamine, and N-acetylgalactosamine. We systematically characterized the roles of each of the predicted 23 components of phosphotransferase system (PTS) with the respective in-frame deletion mutants and defined medium containing specific PTS sugar. In addition, PtsH was identified as the crucial PTS component potentiating the utilization of all the tested PTS sugars. Intriguingly, we also found that PtsH while not Fpr was involved in T3SS gene expression and was essential for the pathogenesis of E. piscicida. To corroborate this, His15 and Ser46, the two established PtsH residues involved in phosphorylation cascade, showed redundant roles in regulating T3SS yields. Moreover, PtsH was shown to facilitate mannose uptake and transform it into mannose-6-phosphate, an allosteric substrate established to activate EvrA to augment bacterial virulence. Collectively, our observations provide new insights into the roles of PTS reciprocally regulating carbohydrate metabolism and virulence gene expression. KEY POINTS: • PTS components' roles for sugar uptake are systematically determined in Edwardsiella piscicida. • PtsH is involved in saccharides uptake and in the regulation of E. piscicida's T3SS expression. • PtsH phosphorylation at His15 and Ser46 is essential for the T3SS expression and virulence.
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http://dx.doi.org/10.1007/s00253-022-11848-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8881556PMC
March 2022

Traditional Chinese Medicine Decoctions Improve Longevity Following Diagnosis with Stage IV Esophageal Squamous Cell Carcinoma: A Retrospective Analysis.

Int J Gen Med 2022 16;15:1665-1675. Epub 2022 Feb 16.

Oncology Department, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou, Henan Province, People's Republic of China.

Objective: Traditional Chinese medicine (TCM) is an ancient form of personalized medicine and may improve morbidity and mortality in patients with esophageal cancer. This retrospective study aimed to evaluate the utility of TCM in the treatment of stage IV esophageal squamous cell carcinoma (SCC).

Methods: We collected the medical records of patients with stage IV SCC admitted to Henan Provincial Hospital of Traditional Chinese Medicine and Linzhou Hospital of Traditional Chinese Medicine between July 2017 and June 2020. We used univariate and multivariate analyses to determine if the use of TCM improved patient prognosis. Moreover, cluster analysis was used to classify the patients according to TCM syndrome type and identify the most frequently used combinations of remedies.

Results: After that 402 patients were included in PSM, of which 196 (48.8%) were treated with traditional Chinese medicine. TCM prolonged the survival time of patients with stage IV esophageal SCC (=0.084), and was an independently associated with prognosis as demonstrated by Cox multivariate regression analysis [risk ratio (RR) =0.543, 95% confidence interval (CI): 0.390-0.755, <0.001]. Association analysis revealed 75 cases (38.26%) had obstruction of phlegm and qi syndrome, 53 cases (27.04%) had phlegm and blood stasis syndrome, 38 cases (19.39%) had yang-qi deficiency syndrome, and 30 cases (15.31%) had heat retention and fluid consumption syndrome.

Conclusion: Treatment with TCM derived therapies may increase the survival time of patients with stage IV esophageal SCC. Since these patients were diagnosed with different TCM syndromes, individualized TCM therapy is essential for improving symptoms and survival.
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http://dx.doi.org/10.2147/IJGM.S346536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8858954PMC
February 2022

Neutrophils in neutrophilic dermatoses: Emerging roles and promising targeted therapies.

J Allergy Clin Immunol 2022 04 18;149(4):1203-1205. Epub 2022 Feb 18.

Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2022.02.008DOI Listing
April 2022

The dynamics of cell death patterns and regeneration during acute liver injury in mice.

FEBS Open Bio 2022 05 5;12(5):1061-1074. Epub 2022 Mar 5.

The School of Medicine, NanKai University, Tianjin, China.

Acute liver injury is a serious clinical syndrome with multiple causes and unclear pathological process. Here, CCl - and D-galactosamine/lipopolysaccharide (D-gal/LPS)-induced acute liver injury was established to explore the cell death patterns and determine whether or not liver regeneration occurred. In CCl -induced hepatic injury, three phases, including the early, progressive, and recovery phase, were considered based on alterations of serum transaminases and liver morphology. Moreover, in this model, cytokines exhibited double-peak fluctuations; apoptosis and pyroptosis persisted throughout all phases; autophagy occurred in the early and the progressive phases; and sufficient and timely hepatocyte regeneration was observed only during the recovery phase. All of these phenomena contribute to mild liver injury and subsequent regeneration. Strikingly, only the early and progressive phases were observed in the D-gal/LPS model. Slight pyroptosis occurred in the early phase but diminished in the progressive phase, while apoptosis, reduced autophagy, and slight but subsequently diminished regeneration occurred only during the progressive phase, accompanied by a strong cytokine storm, resulting in severe liver injury with high mortality. Taken together, our work reveals variable modes and dynamics of cell death and regeneration, which lead to different consequences for mild and severe acute liver injury, providing a helpful reference for clinical therapy and prognosis.
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http://dx.doi.org/10.1002/2211-5463.13383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9063440PMC
May 2022

Design of a mutation-integrated trimeric RBD with broad protection against SARS-CoV-2.

Cell Discov 2022 Feb 15;8(1):17. Epub 2022 Feb 15.

The Sixth Laboratory, National Vaccine and Serum Institute (NVSI), Beijing, China.

The continuous emergence of SARS-CoV-2 variants highlights the need of developing vaccines with broad protection. Here, according to the immune-escape capability and evolutionary convergence, the representative SARS-CoV-2 strains carrying the hotspot mutations were selected. Then, guided by structural and computational analyses, we present a mutation-integrated trimeric form of spike receptor-binding domain (mutI-tri-RBD) as a broadly protective vaccine candidate, which combined heterologous RBDs from different representative strains into a hybrid immunogen and integrated immune-escape hotspots into a single antigen. When compared with a homo-tri-RBD vaccine candidate in the stage of phase II trial, of which all three RBDs are derived from the SARS-CoV-2 prototype strain, mutI-tri-RBD induced significantly higher neutralizing antibody titers against the Delta and Beta variants, and maintained a similar immune response against the prototype strain. Pseudo-virus neutralization assay demonstrated that mutI-tri-RBD also induced broadly strong neutralizing activities against all tested 23 SARS-CoV-2 variants. The in vivo protective capability of mutI-tri-RBD was further validated in hACE2-transgenic mice challenged by the live virus, and the results showed that mutI-tri-RBD provided potent protection not only against the SARS-CoV-2 prototype strain but also against the Delta and Beta variants.
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http://dx.doi.org/10.1038/s41421-022-00383-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8847466PMC
February 2022
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