Publications by authors named "Jingjing Huang"

321 Publications

FMR1 is identified as an immune-related novel prognostic biomarker for renal clear cell carcinoma: A bioinformatics analysis of TAZ/YAP.

Math Biosci Eng 2022 Jun;19(9):9295-9320

The Key Laboratory of Model Animal and Stem Cell Biology in Hunan Province, Hunan Normal University, Changsha 410013, Hunan, China.

WW domain-containing transcription regulator 1 (TAZ, or WWTR1) and Yes-associated protein 1 (YAP) are both important effectors of the Hippo pathway and exhibit different functions. However, few studies have explored their co-regulatory mechanisms in kidney renal clear cell carcinoma (KIRC). Here, we used bioinformatics approaches to evaluate the co-regulatory roles of TAZ/YAP and screen novel biomarkers in KIRC. GSE121689 and GSE146354 were downloaded from the GEO. The limma was applied to identify the differential expression genes (DEGs) and the Venn diagram was utilized to screen co-expressed DEGs. Co-expressed DEGs obtained the corresponding pathways through GO and KEGG analysis. The protein-protein interaction (PPI) network was constructed using STRING. The hub genes were selected applying MCODE and CytoHubba. GSEA was further applied to identify the hub gene-related signaling pathways. The expression, survival, receiver operating character (ROC), and immune infiltration of the hub genes were analyzed by HPA, UALCAN, GEPIA, pROC, and TIMER. A total of 51 DEGs were co-expressed in the two datasets. The KEGG results showed that the enriched pathways were concentrated in the TGF-β signaling pathway and endocytosis. In the PPI network, the hub genes (STAU2, AGO2, FMR1) were identified by the MCODE and CytoHubba. The GSEA results revealed that the hub genes were correlated with the signaling pathways of metabolism and immunomodulation. We found that STAU2 and FMR1 were weakly expressed in tumors and were negatively associated with the tumor stages. The overall survival (OS) and disease-free survival (DFS) rate of the high-expressed group of FMR1 was greater than that of the low-expressed group. The ROC result exhibited that FMR1 had certainly a predictive ability. The TIMER results indicated that FMR1 was positively correlated to immune cell infiltration. The abovementioned results indicated that TAZ/YAP was involved in the TGF-β signaling pathway and endocytosis. FMR1 possibly served as an immune-related novel prognostic gene in KIRC.
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http://dx.doi.org/10.3934/mbe.2022432DOI Listing
June 2022

Clinical validation of a multiplex droplet digital PCR for diagnosing suspected bloodstream infections in ICU practice: a promising diagnostic tool.

Crit Care 2022 08 8;26(1):243. Epub 2022 Aug 8.

Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, China.

Background: Droplet digital PCR (ddPCR) has emerged as a promising tool of pathogen detection in bloodstream infections (BSIs) in critical care medicine. However, different ddPCR platforms have variable sensitivity and specificity for diverse microorganisms at various infection sites. There is still a lack of prospective clinical studies aimed at validating and interpreting the discrepant ddPCR results for diagnosing BSI in intensive care unit (ICU) practice.

Methods: A prospective diagnostic study of multiplex ddPCR panels was conducted in a general ICU from May 21, 2021, to December 22, 2021. Paired blood cultures (BCs) and ddPCRs (2.5 h) were obtained synchronously to detect the 12 most common BSI pathogens and three antimicrobial resistance (AMR) genes. Firstly, ddPCR performance was compared to definite BSI. Secondly, clinical validation of ddPCR was compared to composite clinical diagnosis. Sensitivity, specificity, and positive and negative predictive values were calculated. Thirdly, the positive rate of AMR genes and related analysis was presented.

Results: A total of 438 episodes of suspected BSIs occurring in 150 critical patients were enrolled. BC and ddPCR were positive for targeted bacteria in 40 (9.1%) and 180 (41.1%) cases, respectively. There were 280 concordant and 158 discordant. In comparison with BCs, the sensitivity of ddPCR ranged from 58.8 to 86.7% with an aggregate of 72.5% in different species, with corresponding specificity ranging from 73.5 to 92.2% with an aggregate of 63.1%. Furthermore, the rate of ddPCR+/BC- results was 33.6% (147/438) with 87.1% (128 of 147) cases was associated with probable (n = 108) or possible (n = 20) BSIs. When clinically diagnosed BSI was used as true positive, the final sensitivity and specificity of ddPCR increased to 84.9% and 92.5%, respectively. In addition, 40 bla, 3bla, and 38 mecA genes were detected, among which 90.5% were definitely positive for bla. Further, 65.8% specimens were predicted to be mecA-positive in Staphylococcus sp. according to all microbiological analysis.

Conclusions: The multiplexed ddPCR is a flexible and universal platform, which can be used as an add-on complementary to conventional BC. When combined with clinical infection evidence, ddPCR shows potential advantages for rapidly diagnosing suspected BSIs and AMR genes in ICU practice.
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http://dx.doi.org/10.1186/s13054-022-04116-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9358819PMC
August 2022

Human Nasal Organoids Model SARS-CoV-2 Upper Respiratory Infection and Recapitulate the Differential Infectivity of Emerging Variants.

mBio 2022 Aug 8:e0194422. Epub 2022 Aug 8.

Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Konggrid.194645.b, Pokfulam, Hong Kong, China.

The human upper respiratory tract, specifically the nasopharyngeal epithelium, is the entry portal and primary infection site of respiratory viruses. Productive infection of SARS-CoV-2 in the nasal epithelium constitutes the cellular basis of viral pathogenesis and transmissibility. Yet a robust and well-characterized model of the nasal epithelium remained elusive. Here we report an organoid culture system of the nasal epithelium. We derived nasal organoids from easily accessible nasal epithelial cells with a perfect establishment rate. The derived nasal organoids were consecutively passaged for over 6 months. We then established differentiation protocols to generate 3-dimensional differentiated nasal organoids and organoid monolayers of 2-dimensional format that faithfully simulate the nasal epithelium. Moreover, when differentiated under a slightly acidic pH, the nasal organoid monolayers represented the optimal correlate of the native nasal epithelium for modeling the high infectivity of SARS-CoV-2, superior to all existing organoid models. Notably, the differentiated nasal organoid monolayers accurately recapitulated higher infectivity and replicative fitness of the Omicron variant than the prior variants. SARS-CoV-2, especially the more transmissible Delta and Omicron variants, destroyed ciliated cells and disassembled tight junctions, thereby facilitating virus spread and transmission. In conclusion, we establish a robust organoid culture system of the human nasal epithelium for modeling upper respiratory infections and provide a physiologically-relevant model for assessing the infectivity of SARS-CoV-2 emerging variants. An model of the nasal epithelium is imperative for understanding cell biology and virus-host interaction in the human upper respiratory tract. Here we report an organoid culture system of the nasal epithelium. Nasal organoids were derived from readily accessible nasal epithelial cells with perfect efficiency and stably expanded for more than 6 months. The long-term expandable nasal organoids were induced maturation into differentiated nasal organoids that morphologically and functionally simulate the nasal epithelium. The differentiated nasal organoids adequately recapitulated the higher infectivity and replicative fitness of SARS-CoV-2 emerging variants than the ancestral strain and revealed viral pathogenesis such as ciliary damage and tight junction disruption. Overall, we established a human nasal organoid culture system that enables a highly efficient reconstruction and stable expansion of the human nasal epithelium in culture plates, thus providing a facile and robust tool in the toolbox of microbiologists.
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http://dx.doi.org/10.1128/mbio.01944-22DOI Listing
August 2022

The TPR domain of PgaA is a multifunctional scaffold that binds PNAG and modulates PgaB-dependent polymer processing.

PLoS Pathog 2022 Aug 5;18(8):e1010750. Epub 2022 Aug 5.

Program in Molecular Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada.

The synthesis of exopolysaccharides as biofilm matrix components by pathogens is a crucial factor for chronic infections and antibiotic resistance. Many periplasmic proteins involved in polymer processing and secretion in Gram-negative synthase dependent exopolysaccharide biosynthetic systems have been individually characterized. The operons responsible for the production of PNAG, alginate, cellulose and the Pel polysaccharide each contain a gene that encodes an outer membrane associated tetratricopeptide repeat (TPR) domain containing protein. While the TPR domain has been shown to bind other periplasmic proteins, the functional consequences of these interactions for the polymer remain poorly understood. Herein, we show that the C-terminal TPR region of PgaA interacts with the de-N-acetylase domain of PgaB, and increases its deacetylase activity. Additionally, we found that when the two proteins form a complex, the glycoside hydrolase activity of PgaB is also increased. To better understand structure-function relationships we determined the crystal structure of a stable TPR module, which has a conserved groove formed by three repeat motifs. Tryptophan quenching, mass spectrometry analysis and molecular dynamics simulation studies suggest that the crystallized TPR module can bind PNAG/dPNAG via its electronegative groove on the concave surface, and potentially guide the polymer through the periplasm towards the porin for export. Our results suggest a scaffolding role for the TPR domain that combines PNAG/dPNAG translocation with the modulation of its chemical structure by PgaB.
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http://dx.doi.org/10.1371/journal.ppat.1010750DOI Listing
August 2022

An Antibody Neutralization Determinant on Domain III and the First α-Helical Domain in the Stem-Anchor Region of Tembusu Virus Envelope Protein.

J Immunol 2022 Jul 25. Epub 2022 Jul 25.

Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China

Previous studies identified three neutralizing epitopes on domains I, II, and III of the Tembusu virus (TMUV) envelope (E). More evidence is needed to understand the molecular basis of Ab-mediated neutralization and protection against TMUV. In this study, we observed a neutralizing mAb, 6C8, that neutralized TMUV infection primarily by inhibiting cell attachment. In immunofluorescence assays, 6C8 recognized the premembrane and E proteins coexpressed in HEK-293T cells, but failed to react with premembrane or E expressed individually. Epitope mapping identified nine E protein residues positioned on BC/EF loops and F/G strands in domain III and the first α-helical domain in the stem region. Further investigation with mutant viruses showed that 6C8 pressure resulted in mutations at residues 330 of BC loop and 409 of the first α-helical domain, although 6C8 only exhibited a moderate neutralizing activity in BHK-21 cells and a weak protective activity in BALB/c mice and Shaoxing duck models. Mutations A330S and T409M conferred high- and low-level 6C8 resistance, respectively, whereas the combination of A330S and T409M mutations conferred moderate-level 6C8 resistance. As a result, a quasispecies comprising three groups of antigenic variants appeared in BHK-21 cell-derived viral stocks after repeated passages of TMUV strain Y in the presence of 6C8 treatment. Taken together, these findings have raised a concern about Ab-induced antigenic variations in vivo, and they have revealed information concerning the conformational structure of the 6C8 epitope and its role in constraint on antigenic variations. The present work contributes to a better understanding of the complexity of the TMUV immunogen.
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http://dx.doi.org/10.4049/jimmunol.2200226DOI Listing
July 2022

Adenosine monophosphate deaminase modulates BIN2 activity through hydrogen peroxide-induced oligomerization.

Plant Cell 2022 Jul 25. Epub 2022 Jul 25.

Department of Plant Biotechnology and Bioinformatics, Ghent University, 9052 Ghent, Belgium.

The Arabidopsis thaliana GSK3-like kinase, BRASSINOSTEROID-INSENSITIVE2 (BIN2) is a key negative regulator of brassinosteroid (BR) signaling and a hub for crosstalk with other signaling pathways. However, the mechanisms controlling BIN2 activity are not well understood. Here we performed a forward genetic screen for resistance to the plant-specific GSK3 inhibitor bikinin and discovered that a mutation in the ADENOSINE MONOPHOSPHATE DEAMINASE (AMPD)/EMBRYONIC FACTOR1 (FAC1) gene reduces the sensitivity of Arabidopsis seedlings to both bikinin and BRs. Further analyses showed that AMPD modulates BIN2 activity by regulating its oligomerization in a hydrogen peroxide (H2O2)-dependent manner. Exogenous H2O2 induced the formation of BIN2 oligomers with a decreased kinase activity and an increased sensitivity to bikinin. By contrast, AMPD activity inhibition reduces the cytosolic reactive oxygen species (ROS) levels and the amount of BIN2 oligomers, correlating with the decreased sensitivity of Arabidopsis plants to bikinin and BRs. Furthermore, we showed that BIN2 phosphorylates AMPD to possibly alter its function. Our results reveal the existence of a H2O2 homeostasis-mediated regulation loop between AMPD and BIN2 that fine-tunes the BIN2 kinase activity to control plant growth and development.
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http://dx.doi.org/10.1093/plcell/koac203DOI Listing
July 2022

Research on Methods Decreasing Pesticide Waste Based on Plant Protection Unmanned Aerial Vehicles: A Review.

Front Plant Sci 2022 7;13:811256. Epub 2022 Jul 7.

Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.

In plant protection, the increasing maturity of unmanned aerial vehicle (UAV) technology has greatly increased efficiency. UAVs can adapt to multiple terrains and do not require specific take-off platforms. They do well, especially in farmland areas with rugged terrain. However, due to the complex flow field at the bottom of a UAV, some of the droplets will not reach the surface of a plant, which causes pesticide waste and environmental pollution. Droplet deposition is a good indicator of the utilization rate of pesticides; therefore, this review describes recent studies on droplet deposition for further method improvement. First, this review introduces the flight altitude, speed, and environmental factors that affect pesticide utilization efficiency and then summarizes methods to improve pesticide utilization efficiency from three aspects: nozzles, electrostatic sprays, and variable spray systems. We also point out the possible direction of algorithm development for a UAV's precision spray.
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http://dx.doi.org/10.3389/fpls.2022.811256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301381PMC
July 2022

Oral-Gut Microbiome Analysis in Patients With Metabolic-Associated Fatty Liver Disease Having Different Tongue Image Feature.

Front Cell Infect Microbiol 2022 29;12:787143. Epub 2022 Jun 29.

The Clinical Medical College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, China.

Objective: The objective of this study was to identify the biological correlation between the tongue coating color and oral and gut micro-characteristics in metabolic-associated fatty liver disease (MAFLD) patients.

Method: The characteristics of the tongue coating were examined using an automatic tongue diagnosis system. Tongue coating and stool samples were collected from 38 MAFLD patients, and 16S rDNA full-length assembly sequencing technology (16S-FAST) was used for bioinformatic analysis.

Results: Twenty-two and 16 subjects were included in two distinct clusters according to the white/yellow color of the tongue coating, which was assessed by the values of the image. Upon analyzing the microorganisms in the tongue coating, 66 and 62 pathognomonic bacterial genera were found in the White and Yellow Coating Groups, respectively. The abundance of positively correlated with the values of the tongue coating in the White Coating Group, while , , and abundance was significantly correlated with the values in the Yellow Coating Group. Function prediction mainly showed the involvement of protein families related to BRITE hierarchies and metabolism. The MHR (MONO%/high-density lipoprotein cholesterol) of the Yellow Coating Group was higher than that of the White Coating Group.

Conclusion: In MAFLD patients, lower values and higher values are indicators of a yellow tongue coating. There were also significant differences in the flora of different tongue coatings, with corresponding changes in the intestinal flora, indicating a correlation between carbohydrate metabolism disorders and inflammation in the oral microbiome.
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http://dx.doi.org/10.3389/fcimb.2022.787143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277304PMC
June 2022

Prevention of Severe Respiratory Tract Infection and Prognosis in Neurosurgical Patients with Severe Tracheotomy Based on 5E Rehabilitation Nursing Model.

Comput Math Methods Med 2022 5;2022:2727679. Epub 2022 Jul 5.

Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Donghu Road-169, Wuhan, Hubei Province 430071, China.

Background: Continuous nursing based on 5E rehabilitation mode can improve the physiology and psychology of patients to some extent. The purpose of this study was to explore the effect of continuous nursing of 5E rehabilitation mode on the prevention and prognosis of severe respiratory tract infection in patients with severe tracheotomy in neurosurgery.

Objective: To explore the effect of 5E rehabilitation nursing model on the prevention of severe respiratory tract infection and prognosis in patients with severe tracheotomy in neurosurgery.

Methods: The starting and ending time of this study is from February 2019 to July 2021. In this paper, 60 patients with severe tracheotomy were divided into the control group and research group according to random number table method. The former group received routine nursing, and the latter group received rehabilitation nursing model based on 5E. The patients' satisfaction, oxygenation index, partial pressure of carbon dioxide, partial pressure of oxygen, SAS, SDS score, incidence of severe respiratory tract infection, and quality of life scores were compared.

Results: The nursing satisfaction of the research group was higher than that of the control group ( < 0.05). 24 hours after weaning, the oxygenation index and partial pressure of oxygen in the research group were higher than those in the control group, while the partial pressure of carbon dioxide in the research group was lower than that in the control group ( < 0.05). After nursing, the scores of self-rating anxiety scale and self-rating depression scale in the research group were lower than those in the control group, and the difference was statistically significant ( < 0.05). The incidence of severe respiratory tract infection in the research group was significantly lower than that in the control group ( < 0.05). After nursing, the scores of physiological function, psychological function, social function, and health self-cognition in the research group were lower than those in the control group ( < 0.05).

Conclusion: The nursing program of neurosurgical patients with severe tracheotomy based on 5E rehabilitation model can effectively enhance patients' nursing satisfaction, activities of daily living, anxiety, and depression and promote the prognosis.
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http://dx.doi.org/10.1155/2022/2727679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9276491PMC
July 2022

Partitioning the lung field based on the depth ratio in three-dimensional space.

Transl Lung Cancer Res 2022 Jun;11(6):1165-1175

Department of Thoracic Surgery, Jiangsu Province Hospital and The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Background: To explore the feasibility of the depth ratio method partitioning the lung parenchyma and the depth distribution of lung nodules in pulmonary segmentectomy.

Methods: Based on the measurement units, patients were allocated to the chest group, the lobar group, and the symmetrical 3 sectors group. In each unit, the center of the respective bronchial cross-section was set as the starting point (O). Connecting the O point with the center of the lesion (A) and extending to the endpoint (B) on the pleural, the radial line (OB) was trisected to divide the outer, middle, and inner regions. The depth ratio and relevant regional distribution were simultaneously verified using 2-dimensional (2D) coronal, sagittal, and axial computed tomography images and 3-dimensional (3D) reconstruction images.

Results: Two hundred and nine patients were included in this study. The median age was 53 (IQR, 44.5-62) years and 64 were males. The intra-group consistency of the depth ratio region partition was 100%. The consistency of the inter-group region partition differed among the three groups (Kappa values 0.511, 0.517, and 0.923). The chest group, lobar group, and symmetrical 3 sectors group had 69.4%, 26.3%, and 4.8% mediastinum disturbance, respectively (P<0.001).

Conclusions: The depth ratio method in the symmetrical 3 sectors of the lung maximally eliminated the disturbance of the mediastinal structures and more accurately trisected the lung parenchymal in 3D space. Sublobar resection based on subsegments strategy is feasible for outer 2/3 pulmonary nodules when depth ratio is used as the measurement method.
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http://dx.doi.org/10.21037/tlcr-22-391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271427PMC
June 2022

Long-Term Antipsychotic Effectiveness and Comparison of the Efficacy of Monotherapy and Polypharmacy in Schizophrenia: A 3-Years Follow-Up "Real World" Study in China.

Front Pharmacol 2022 13;13:860713. Epub 2022 Jun 13.

Department of Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Discontinuation of antipsychotic treatment is a common problem in patients with schizophrenia and could reduce the effectiveness of treatment. Time to discontinuation (TTD) is one of the indicators of compliance and may also be an effective indicator of medication efficacy. The aim of the study was to compare the clinical effectiveness of quetiapine, olanzapine, risperidone, and aripiprazole in the real-world treatment of schizophrenia with 3-years follow-up. A multi-center, open, cohort, prospective, real-world study was conducted. 706 patients were analyzed without intervention in medication selection and use, followed up for 3 years. Kaplan-Meier survival curves were used to draw the treatment discontinuation rates (TDR) curves at each time point. Cox proportional hazard regression model was used to assess the relative risk of TTD of antipsychotics. There was a significant difference among monotherapy groups in all-cause antipsychotic treatment discontinuation ( = 0.0057). Among the four medications, the TDR of risperidone was the highest. Compared with polypharmacy, except for aripiprazole, the TDR of other three monotherapy medications were lower than that of polypharmacy, and olanzapine was statistically different ( = 0.0325). The cox regression analysis showed that after correction of Hochberg with multiple tests, only olanzapine had a relative risk lower than risperidone ( < 0.0083). The findings indicated that risperidone monotherapy and polypharmacy had the highest TDR and the shortest TTD. Olanzapine monotherapy had a relative risk lower than risperidone and was superior to polypharmacy.
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http://dx.doi.org/10.3389/fphar.2022.860713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234304PMC
June 2022

Does Shift in Vegetation Abundance After Nitrogen and Phosphorus Additions Play a Key Role in Regulating Fungal Community Structure in a Northern Peatland?

Front Microbiol 2022 9;13:920382. Epub 2022 Jun 9.

Key Laboratory of Geographical Processes and Ecological Security in Changbai Mountains, Ministry of Education, School of Geographical Sciences, Northeast Normal University, Changchun, China.

Soil fungal communities are key players in biogeochemical processes of peatlands, which are important carbon stocks globally. Although it has been elucidated that fungi are susceptible to environmental changes, little is known about the intricate and interactive effect of long-term nitrogen (N) and phosphorus (P) enrichment on fungal community structure in northern peatlands. In this study, we compared a short- (2 years) with a long-term (10 years) fertilization experiment in a peatland complex in northeastern China to assess how N and/or P additions influence fungal community structure. The results showed that fungal community composition and diversity were altered by N addition, without a significant interactive effect with P addition. Not only the long-term but also the short-term nutrient addition could change the abundance of different plant functional types. However, there were no strong cascading effects on the fungal community in any of the fertilization experiments. Long-term nutrient addition showed a stronger effect on the relative abundance of different fungal functional guilds; an increase in the relative abundance of saprotrophs after fertilization did not jeopardize mycorrhizal fungi. Moreover, the decline in cover after long-term N addition did not parallel changes in the relative abundance of -associated fungi (, , , and ). Given that short- and long-term fertilization showed strongly contrasting effects on fungal community structure, our study highlights the necessity of assessing the long-term effects of nutrient enrichment on the association between vegetation and fungal community in peatland ecosystems. Future research priorities should emphasize the connection between the community structure of fungal functional guilds and their functionality, which is of paramount importance to better understand their influences on C storage in the face of uncertain N and P deposition regimes.
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http://dx.doi.org/10.3389/fmicb.2022.920382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9224414PMC
June 2022

Ligand Evolution in the Photoactivatable Platinum(IV) Anticancer Prodrugs.

Front Chem 2022 9;10:876410. Epub 2022 Jun 9.

College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.

Photoactivatable Pt(IV) anticancer prodrugs with the structure of [Pt(N)(N)(L)(L)(A)(A)], where N and N are non-leaving nitrogen donor ligands, L and L are leaving ligands, and A and A are axial ligands, have attracted increasing attention due to their promising photo-cytotoxicity even to cisplatin-resistant cancer cells. These photochemotherapeutic prodrugs have high dark-stability under physiological conditions, while they can be activated by visible light restrained at the disease areas, as a consequence showing higher spatial and temporal controllability and much more safety than conventional chemotherapy. The coordinated ligands to the Pt center have been proved to be pivotal in determining the function and activity of the photoactivatable Pt(IV) prodrugs. In this review, we will focus on the development of the coordinated ligands in such Pt(IV) prodrugs and discuss the effects of diverse ligands on their photochemistry and photoactivity as well as the future evolution directions of the ligands. We hope this review can help to facilitate the design and development of novel photoactivatable Pt(IV) anticancer prodrugs.
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http://dx.doi.org/10.3389/fchem.2022.876410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218644PMC
June 2022

Synthesis of dihydrofuran-3-one and 9,10-phenanthrenequinone hybrid molecules and biological evaluation against colon cancer cells as selective Akt kinase inhibitors.

Mol Divers 2022 Jun 25. Epub 2022 Jun 25.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.

A series of dihydrofuran-3-one and 9,10-phenanthrenequinone hybrid compounds were synthetized through a one-pot gold-catalyzed oxidative cyclization and Aldol-type addition cascade reaction of homopropargylic alcohols with 9,10-phenanthrenequinone. The cytotoxicity of newly synthesized compounds was evaluated in CCK8 assay against different human cancer cells, showing significantly antiproliferative activity against tested tumor cell lines with a lowest IC value of 0.92 μM over HCT-116. Further investigation revealed that the treatment of HCT-116 cell line with the promising compound 4c induced cell death as a selective Akt inhibitor. In addition, controlled experiments and molecular docking study suggested that the significant antitumor activity might be attributed to the unique hybrid structure, which implied the promising potential of this dual heterocycle hybrid method in the discovery of novel bioactive molecules with structural diversity.
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http://dx.doi.org/10.1007/s11030-022-10458-wDOI Listing
June 2022

Personalized College English Learning Based on Deep Learning under the Background of Big Data.

Authors:
Jingjing Huang

Comput Intell Neurosci 2022 10;2022:7361746. Epub 2022 Jun 10.

Zhejiang University of Science & Technology, Hangzhou, Zhejiang 310023, China.

Generally, in-depth learning has been extensively employed in numerous industries to enhance the growth of economic globalization since the dawn of the big data age. At the same time, the demand for foreign language talent has risen dramatically, and more and more businesses are steadily raising their English proficiency standards. International interactions, as well as scientific and technical exchanges, are influenced by English communicating competence. As a result, colleges and universities place a high value on students studying English. However, English learning is also a compulsory course in Colleges and universities, which is different from other courses. Therefore, in setting teaching objectives, arranging teaching activities, and compiling teaching contents, we should highlight students' personalized needs and formulate learning plans in combination with the individual requirements of each student. Aiming at this problem, this paper adopts the deep learning method to study the personalized learning of College English. Deep learning algorithm utilization in the development of college students' English learning reduces teachers' workload and focuses more on students' personalized needs, which is beneficial to teachers' teaching and students' learning. By analyzing the deep learning neural network model, the process of English speech recognition is described, and the characteristic parameters of English speech are extracted. Then compare and explain the characteristics of deep learning and shallow learning, analyze the relationship between them, and clarify the route of deep learning. Finally, the effect of College Students' personalized learning is analyzed by random sampling, and the effect of College English personalized learning based on deep learning is explained from two aspects: listening effect and reading practice.
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http://dx.doi.org/10.1155/2022/7361746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9205700PMC
June 2022

A bipotential organoid model of respiratory epithelium recapitulates high infectivity of SARS-CoV-2 Omicron variant.

Cell Discov 2022 Jun 17;8(1):57. Epub 2022 Jun 17.

Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.

The airways and alveoli of the human respiratory tract are lined by two distinct types of epithelium, which are the primary targets of respiratory viruses. We previously established long-term expanding human lung epithelial organoids from lung tissues and developed a 'proximal' differentiation protocol to generate mucociliary airway organoids. However, a respiratory organoid system with bipotential of the airway and alveolar differentiation remains elusive. Here we defined a 'distal' differentiation approach to generate alveolar organoids from the same source for the derivation of airway organoids. The alveolar organoids consisting of type I and type II alveolar epithelial cells (AT1 and AT2, respectively) functionally simulate the alveolar epithelium. AT2 cells maintained in lung organoids serve as progenitor cells from which alveolar organoids derive. Moreover, alveolar organoids sustain a productive SARS-CoV-2 infection, albeit a lower replicative fitness was observed compared to that in airway organoids. We further optimized 2-dimensional (2D) airway organoids. Upon differentiation under a slightly acidic pH, the 2D airway organoids exhibit enhanced viral replication, representing an optimal in vitro correlate of respiratory epithelium for modeling the high infectivity of SARS-CoV-2. Notably, the higher infectivity and replicative fitness of the Omicron variant than an ancestral strain were accurately recapitulated in these optimized airway organoids. In conclusion, we have established a bipotential organoid culture system able to reproducibly expand the entire human respiratory epithelium in vitro for modeling respiratory diseases, including COVID-19.
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http://dx.doi.org/10.1038/s41421-022-00422-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9203776PMC
June 2022

Effect of Nano-SiO/PVA on Corrosion Behavior of Steel Rebar Embedded in High-Volume Fly Ash Mortar under Accelerated Chloride Attack.

Materials (Basel) 2022 May 30;15(11). Epub 2022 May 30.

College of Water Conservancy and Civil Engineering, South China Agricultural University, Guangzhou 510642, China.

In this paper, the influence of Nano-silica (NS) and Polyvinyl alcohol (PVA) fibers on the corrosion behavior of steel rebar embedded in high-volume fly ash cement mortars under accelerated chloride attack was studied by using an impressed voltage technique. The PVA fibers used were 1.0 vol.%, and two mass fractions of cement (50 and 60 wt.%) were replaced by fly ash. Four NS mass fractions (0, 0.5, 1.0, and 1.5 wt.%) were utilized in this paper. In addition, the mono and hybrid effects of NS and PVA on the mechanical properties and water absorption of mortar were also studied. The results showed that the incorporation of PVA and nano-SiO can improve the flexural and compressive strengths of high-volume fly ash mortar. Generally, the flexural and compressive strengths increased with the increase of nano-SiO content. Moreover, the incorporation NS can also reduce the capillary water-absorption rate of cement mortar. The impressed voltage corrosion test indicated that the composite incorporation of nano-SiO and PVA can significantly delay the deterioration process of steel bars in mortar, effectively reducing the steel rebar's corrosion level and increasing the exposure time of the surface crack. With hybrid-incorporation 1.0 vol.% PVA and 1.0 wt.% nano-SiO, the steel rebar had the lowest corrosion degree, which exhibited a mass loss of 49% and increased the broken time by 71% as compared to the control mortar.
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http://dx.doi.org/10.3390/ma15113900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9181953PMC
May 2022

Novel Circulating Tumour Cell-Related Risk Model Indicates Prognosis and Immune Infiltration in Lung Adenocarcinoma.

J Immunol Res 2022 29;2022:6521290. Epub 2022 May 29.

The Key Laboratory of Model Animal and Stem Cell Biology in Hunan Province, Hunan Normal University, Changsha, 410013 Hunan, China.

Background: Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer (LC) and one of the leading causes of cancer-related death worldwide. LUAD has a low survival rate owing to tumour invasion and metastasis. Circulating tumour cells (CTCs) are precursors of distant metastasis, which are considered to adopt the characteristics of cancer stem cells (CSCs). Therefore, analysing the risk factors of LUAD from the perspective of CTCs may provide novel insights into the metastatic mechanisms and may help to develop diagnostic and therapeutic strategies.

Methods: A total of 447 patients from TCGA dataset were included in the training cohort, and 460 patients from the GEO dataset were included in the validation cohort. A CTC-related-gene risk model was constructed using LASSO penalty-Cox analysis, and its predictive value was further verified. Functional enrichment analysis was performed on differentially expressed genes (DEGs), followed by immune correlation analysis based on the results. In addition, western blot, CCK-8 and colony formation assays were used to validate the biological function of in LUAD.

Results: A novel in-silico CTC-related-gene risk model, named the CTCR model, was constructed, which successfully divided patients into the high- and low-risk groups. The prognosis of the high-risk group was worse than that of the low-risk group. ROC analysis revealed that the risk model outperformed traditional clinical markers in predicting the prognosis of patients with LUAD. Further study demonstrated that the identified DEGs were significantly enriched in immune-related pathways. The immune score of the low-risk group was higher than that of the high-risk group. In addition, was found to promote the proliferation of LUAD.

Conclusion: A prognostic risk model based on CTC-related genes was successfully constructed, and the relationship between DEGs and tumour immunity was analysed. In addition, was found to promote the proliferation of LUAD cells.
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http://dx.doi.org/10.1155/2022/6521290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9168189PMC
June 2022

In Vitro Biochemical Analysis of Recombinant Plant Proteins Under Oxidation.

Methods Mol Biol 2022 ;2526:143-160

Department of Plant Biotechnology and Bioinformatics, Ghent University, Ghent, Belgium.

Biochemical analysis is crucial for determining protein functionality changes during various conditions, including oxidative stress conditions. In this chapter, after giving brief guidelines for experimental design, we provide step-by-step instructions to purify recombinant plant proteins from E. coli, to prepare reduced and oxidized proteins for activity assay, and to characterize the protein under reducing and oxidizing conditions, with a focus on thiol-based oxidative modifications, like S-sulfenylation and disulfide formations.
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http://dx.doi.org/10.1007/978-1-0716-2469-2_11DOI Listing
June 2022

A LASSO-derived clinical score to predict severe acute kidney injury in the cardiac surgery recovery unit: a large retrospective cohort study using the MIMIC database.

BMJ Open 2022 06 2;12(6):e060258. Epub 2022 Jun 2.

Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China

Objectives: We aimed to develop an effective tool for predicting severe acute kidney injury (AKI) in patients admitted to the cardiac surgery recovery unit (CSRU).

Design: A retrospective cohort study.

Setting: Data were extracted from the Medical Information Mart for Intensive Care (MIMIC)-III database, consisting of critically ill participants between 2001 and 2012 in the USA.

Participants: A total of 6271 patients admitted to the CSRU were enrolled from the MIMIC-III database.

Primary And Secondary Outcome: Stages 2-3 AKI.

Result: As identified by least absolute shrinkage and selection operator (LASSO) and logistic regression, risk factors for AKI included age, sex, weight, respiratory rate, systolic blood pressure, diastolic blood pressure, central venous pressure, urine output, partial pressure of oxygen, sedative use, furosemide use, atrial fibrillation, congestive heart failure and left heart catheterisation, all of which were used to establish a clinical score. The areas under the receiver operating characteristic curve of the model were 0.779 (95% CI: 0.766 to 0.793) for the primary cohort and 0.778 (95% CI: 0.757 to 0.799) for the validation cohort. The calibration curves showed good agreement between the predictions and observations. Decision curve analysis demonstrated that the model could achieve a net benefit.

Conclusion: A clinical score built by using LASSO regression and logistic regression to screen multiple clinical risk factors was established to estimate the probability of severe AKI in CSRU patients. This may be an intuitive and practical tool for severe AKI prediction in the CSRU.
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http://dx.doi.org/10.1136/bmjopen-2021-060258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9163540PMC
June 2022

Analysis of PANoptosis-Related LncRNA-miRNA-mRNA Network Reveals LncRNA SNHG7 Involved in Chemo-Resistance in Colon Adenocarcinoma.

Front Oncol 2022 12;12:888105. Epub 2022 May 12.

The Key Laboratory of Model Animal and Stem Cell Biology in Hunan Province, Hunan Normal University, Changsha, China.

Colon adenocarcinoma (COAD) is one of the most common malignancies, and its metastatic lesions are the leading cause of death in COAD patients. PANoptosis is a recently identified pathway for programmed cell death implicated in developing COAD. Long non-coding RNAs (lncRNAs) are key regulators of cancer occurrence and progress. Although their function has captured much attention in COAD, the relationship between COAD metastasis-associated lncRNA expression and PANoptosis remains elusive. Therefore, this study aimed to explore the potential regulatory roles of metastasis- and PANoptosis-associated lncRNAs in COAD. Nine lncRNAs associated with metastasis and PANoptosis in COAD were identified from The Cancer Genome Atlas (TCGA) and GEO databases. Their functions were analyzed by multiple bioinformatics methods, and the lncRNA-miRNA-mRNA network was constructed. Multivariate Cox analysis identified one lncRNA (SNHG7) significantly related to COAD prognosis. Subsequent analyses showed its expression correlated with tumor stage and lymph node metastasis. Moreover, drug sensitivity analysis and experiments suggest that lncRNA SNHG7 contributes to drug resistance in COAD. In summary, lncRNA SNHG7 is a potential target for diagnosing and treating COAD and plays a crucial role in regulating apoptosis, metastasis, and drug resistance in COAD.
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http://dx.doi.org/10.3389/fonc.2022.888105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9133343PMC
May 2022

Investigating the Molecular Mechanism of Quercetin Protecting against Podocyte Injury to Attenuate Diabetic Nephropathy through Network Pharmacology, MicroarrayData Analysis, and Molecular Docking.

Evid Based Complement Alternat Med 2022 16;2022:7291434. Epub 2022 May 16.

Department of Pharmacy, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.

Quercetin (QUE), a health supplement, can improve renal function in diabetic nephropathy (DN) rats by ameliorating podocyte injury. Its clinical trial for renal insufficiency in advanced diabetes (NCT02848131) is currently underway. This study aimed to investigate the mechanism of QUE protecting against podocyte injury to attenuate DN through network pharmacology, microarray data analysis, and molecular docking. QUE-associated targets, genes related to both DN, and podocyte injury were obtained from different comprehensive databases and were intersected and analyzed to obtain mapping targets. Candidate targets were identified by constructing network of protein-protein interaction (PPI) of mapping targets and ranked to obtain key targets. The major pathways were obtained from Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) term enrichment analysis of candidate targets via ClueGO plug-in and R project software, respectively. Potential receptor-ligand interactions between QUE and key targets were evaluated via Autodocktools-1.5.6. 41. Candidate targets, of which three key targets (TNF, VEGFA, and AKT1), and the major AGE-RAGE signaling pathway in diabetic complications were ascertained and associated with QUE against podocyte injury in DN. Molecular docking models showed that QUE could closely bind to the key targets. This study revealed that QUE could protect against podocyte injury in DN through the following mechanisms: downregulating inflammatory cytokine of TNF, reducing VEGF-induced vascular permeability, inhibiting apoptosis by stimulating AKT1 phosphorylation, and suppressing the AGE-induced oxidative stress via the AGE-RAGE signaling pathway.
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http://dx.doi.org/10.1155/2022/7291434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9126727PMC
May 2022

Genomic Characterization of a Collected from a Field Tomato Plant in Chengdu, Southwestern China.

Microbiol Resour Announc 2022 Jun 23;11(6):e0029722. Epub 2022 May 23.

Institute of Biotechnology and Nuclear Technology, Sichuan Academy of Agricultural Sciences, Chengdu, Sichuan, China.

Here, we report the genomic sequence and genetic variations of a . The virus isolated from a field tomato (Solanum lycopersicum) plant in Chengdu, southwestern China, was sequenced via both Illumina and Sanger technologies. Phylogeny indicates that its genome is close to the reported virus sequence from collected in 2013 but far from Solanum nigrum collected in 2020.
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http://dx.doi.org/10.1128/mra.00297-22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9202394PMC
June 2022

The Role of English as a Foreign Language Teachers' Mindfulness and Compassion in Fostering Students' Foreign Language Enjoyment.

Authors:
Jingjing Huang

Front Psychol 2022 3;13:899298. Epub 2022 May 3.

School of Foreign Languages, Hefei Normal University, Hefei, China.

With the popularity of positive psychology in English as a Foreign Language (EFL) teaching and learning, learners' positive emotions have attracted great academic attention. Foreign language enjoyment (FLE) is regarded as a constructive emotion and key component for learners' academic engagement that is affected by educators' emotions and psychological attributes. Earlier studies have proved the positive role of educators' mindfulness and compassion in reducing learners' negative feelings, boosting their positive emotions and building a harmonious teacher-student rapport. Through mindful and compassionate training, EFL teachers are skilled at creating a joyful learning atmosphere, showing understanding and support toward learners, as well as inspiring learners with enthusiasm and joy. The present review makes efforts to emphasize the significant effect of EFL teachers' mindfulness and compassion on fostering students' FLE. Moreover, a number of practical implications are provided for EFL teachers, teacher educators, school managers, and future directions are offered for enthusiastic researchers to conduct similar and complementary research in the field of foreign language education.
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http://dx.doi.org/10.3389/fpsyg.2022.899298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9110884PMC
May 2022

CircPCBP2 promotes the stemness and chemoresistance of DLBCL via targeting miR-33a/b to disinhibit PD-L1.

Cancer Sci 2022 Aug 14;113(8):2888-2903. Epub 2022 Jun 14.

Department of Immunotherapy, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan Province, China.

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy with a high relapse rate of up to 40%. The prognosis of the disease needs improvement and requires a understanding of its molecular mechanism. We investigated the mechanisms of DLBCL development and its sensitivity to chemotherapy by focusing on circPCBP2/miR-33a/b/PD-L1 axis. Human DLBCL specimens and cultured cancer cell lines were used. Features of circPCBP2 were systematically characterized through Sanger sequencing, Actinomycin D, RNase R treatment, and FISH. The expression levels of circPCBP2, miR-33a/b, PD-L1, stemness-related markers, ERK/AKT and JAK2/STAT3 signaling were measured using qRT-PCR, western blotting, and immunohistochemistry. Stemness of DLBCL cells was assessed through spheroid formation assay and flow cytometry. Cell viability and apoptosis upon cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) treatment were determined using MTT assay and flow cytometry, respectively. Interactions of circPCBP2-miR-33a/b and miR-33a/b-PD-L1 were validated using dual luciferase activity assay and RNA-RIP. Nude mouse xenograft model was used to assess the function of circPCBP2 in DLBCL growth in vivo. circPCBP2 was upregulated in human DLBCL specimens and cultured DLBCL cells while miR-33a/b was reduced. Knockdown of circPCBP2 or miR-33a/b overexpression inhibited the stemness of DLBCL cells and promoted cancer cell apoptosis upon CHOP treatment. circPCBP2 directly bound with miR-33a/b while miR-33a/b targeted PD-L1 3'-UTR. circPCBP2 disinhibited PD-L1 signaling via sponging miR-33a/b. miR-33a/b inhibitor and activating PD-L1 reversed the effects of circPCBP2 knockdown and miR-33a/b mimics, respectively. circPBCP2 knockdown restrained DLBCL growth in vivo and potentiated the anti-tumor effects of CHOP. In conclusion, circPCBP2 enhances DLBCL cell stemness but suppresses its sensitivity to CHOP via sponging miR-33a/b to disinhibit PD-L1 expression. circPCBP2/miR-33a/b/PD-L1 axis could serve as a diagnosis marker or therapeutic target for DLBCL.
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http://dx.doi.org/10.1111/cas.15402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9357607PMC
August 2022

Case Report: Olaparib Shows Satisfactory Clinical Outcomes Against Small Cell Esophageal Carcinoma With Mutation.

Front Oncol 2022 11;12:808801. Epub 2022 Apr 11.

Department of Thoracic Surgery, Peking Union Medical College Hospital, Beijing, China.

Small cell esophageal carcinoma (SCEC) is a rare, undifferential type of cancer, with a high degree of malignancy and early systemic metastasis. Radio-chemotherapy and surgery have been used as the primary treatment strategies for SCEC, but they both result in poor prognosis. There is need to develop an optimal standard treatment for the disease to improve prognosis and limit the related mortality. In this study, we described identification of driver mutations in , a gene involved in homologous recombination deficiency (HRD) pathway, using next-generation sequencing on primary lesion and peripheral blood of a SCEC patient, who experienced recurrence after resection and radio-chemotherapy. In addition, we subjected the patient to olaparib, a PARP inhibitor, for the treatment of tumor with HRD and obtained a partial response. This is the first evidence implicating olaparib in successful treatment of SCEC with mutation. The findings suggest that targeting mutations in HRD genes using olaparib or actionable genetic mutations using corresponding drugs, may be an effective therapeutic option for SCEC, although this requires further investigation.
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http://dx.doi.org/10.3389/fonc.2022.808801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9036436PMC
April 2022

Mining intrinsic information of convalescent patients after suffering coronavirus disease 2019 in Wuhan.

J Tradit Chin Med 2022 04;42(2):279-288

Hepatic Disease Institute, Hubei Key Laboratory of Theoretical and Applied Research of Liver and Kidney in Traditional Chinese Medicine, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan 430061, China.

Objective: To summarize the potential characteristics of convalescent patients with coronavirus disease 2019 (COVID-19) in China based on emerging clinical tongue data and guide the treatment and recovery of COVID-19 patients from the perspective of Traditional Chinese Medicine tongue diagnosis.

Methods: In this study, we developed and validated radiomics-based and lab-based methods as a novel approach to provide individualized pretreatment evaluation by analyzing different features to mine the orderliness behind tongue data of convalescent patients. In addition, this study analyzed the tongue features of convalescent patients from clinical tongue qualitative values, including thick and thin, fur, peeling, fat and lean, tooth marks and cracked, and greasy and putrid fur.

Results: We included 2164 tongue images in total (34% from day 0, 35.4% from day 14 and 30.6% from day 28) from convalescent patients. The significance results are shown as follows. Firstly, as the recovery time prolongs, the L average values of tongue and coat decrease from 60.21 to 57.18 and from 60.06 to 57.03 respectively. Secondly, the decrease of abnormality rate of tongue coat, included greasy tongue fur, putrid fur, teeth-mark, thick-thin fur, are of significant statistical difference ( < 0.05). Thirdly, the average value of gray-level co-occurrence matrices increases from 0.173 to 0.194, the average value of entropy increases from 0.606 to 0.665, the average value of inverse difference normalized decrease from 0.981 to 0.979, and the average value of dissimilarity decrease from 0.1576 to 0.1828. The details of other radiomics features are describe in results section.

Conclusions: Our experiment shows that patients in different recovery periods have a relationship with quantitative values of tongue images, including L color space of the tongue and coat radiomics features analysis. This relationship can help clinical doctors master the recovery and health of patients as soon as possible and improve their understanding of the potential mechanisms underlying the dynamic changes and mechanisms underlying COVID-19.
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http://dx.doi.org/10.19852/j.cnki.jtcm.20220225.001DOI Listing
April 2022

Establishing Human Lung Organoids and Proximal Differentiation to Generate Mature Airway Organoids.

J Vis Exp 2022 03 23(181). Epub 2022 Mar 23.

Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong; Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park; State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong;

The lack of a robust in vitro model of the human respiratory epithelium hinders the understanding of the biology and pathology of the respiratory system. We describe a defined protocol to derive human lung organoids from adult stem cells in the lung tissue and induce proximal differentiation to generate mature airway organoids. The lung organoids are then consecutively expanded for over 1 year with high stability, while the differentiated airway organoids are used to morphologically and functionally simulate human airway epithelium to a near-physiological level. Thus, we establish a robust organoid model of the human airway epithelium. The long-term expansion of lung organoids and differentiated airway organoids generates a stable and renewable source, enabling scientists to reconstruct and expand the human airway epithelial cells in culture dishes. The human lung organoid system provides a unique and physiologically active in vitro model for various applications, including studying virus-host interaction, drug testing, and disease modeling.
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http://dx.doi.org/10.3791/63684DOI Listing
March 2022

Contributes to TMZ Resistance, Prognosis, and Immune Infiltration in GBM from a Novel Pyroptosis-Associated Risk Signature.

Dis Markers 2022 1;2022:4534080. Epub 2022 Apr 1.

Department of Head and Neck Surgery, Hunan Cancer Hospital, Xiangya School of Medicine, Central South University, Changsha, 410013 Hunan, China.

Background: Pyroptosis is a form of programmed cell death, playing a significant role in cancer. Glioblastoma multiforme (GBM) is the most common malignant brain tumor. The poor prognosis in GBM due to temozolomide (TMZ) resistance has been widely discussed. Such being the case, the correlation between TMZ resistance and pyroptosis is seldom investigated. On this basis, this paper aims to explore the potential prognostic value of genes related to TMZ resistance and pyroptosis as well as their relationship to the immune microenvironment in GBM.

Methods: A total of 103 patients from TCGA were assigned to a training cohort; 190 from CGGA were assigned to a validation cohort. The prognostic risk model reflecting pyroptosis and TMZ resistance was built from the training cohort using multivariate Cox regression and performed validation. RT-qPCR was used to examine the expression of 4 genes from the risk signature. was selected for overexpression and verified using the western blot. The TMZ IC50 of -overexpressed cell lines was determined by CCK8.

Results: A four genes-based risk signature was established and validated, separating GBM patients into high- and low-risk groups. Compared with the low-risk group, the high-risk group presented worse clinical survival outcomes. Its differential expressed genes were enriched in immune-related pathways and closely related to the immune microenvironment. Moreover, RT-qPCR results suggested that , , and were significantly upregulated in TMZ-resistant strains, while was downregulated. overexpressed GBM cell lines had higher TMZ IC50, implying an increased resistance of TMZ.

Conclusion: A novel gene signature relevant to pyroptosis and TMZ resistance was constructed and could be used for the prognosis of GBM. The four genes from the risk model might play a potential role in antitumor immunity and serve as therapeutic targets for GBM.
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http://dx.doi.org/10.1155/2022/4534080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8993549PMC
April 2022

A bifunctional electrochemical sensor for simultaneous determination of electroactive and non-electroactive analytes: A universal yet very effective platform serving therapeutic drug monitoring.

Biosens Bioelectron 2022 Jul 29;208:114233. Epub 2022 Mar 29.

Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. Electronic address:

A novel electrochemical sensor for therapeutic drug monitoring (TDM) of antibiotic Zavicefta was developed in this work. The main components of Zavicefta are ceftazidime (CFZ) and avibactam (AVI), wherein CFZ can be oxidized directly on electrode surface, while AVI is non-electroactive. In order to realize the simultaneous detection of the two analytes on one sensor, we elaborately constructed a dual-template molecularly imprinted polymer (MIP) modified electrode with CFZ and AVI as the templates, and further developed a dual-signal strategy. During detection, due to the inhibition effect caused by rebinding of MIP to the targets, the peak current of probe ferricyanide ([Fe(CN)]) showed obvious suppression. Meanwhile, a new peak appeared, which originated from the oxidation of CFZ. The proposed sensor presented a wide linear range of 50-1000 μM for CFZ and 1-1000 μM for AVI, with the respective detection limit of 35 μM and 0.5 μM (S/N = 3). Owing to the imprinting effect of MIP, the sensor displayed excellent selectivity and anti-interference ability, which was successfully applied for TDM of CFZ and AVI in human serum and a live rabbit. The results agreed well with those from HPLC. This work is expected to offer a promising avenue for simultaneous measurement of electroactive and non-electroactive substances, and extend the potential of electrochemical sensors in medical field.
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http://dx.doi.org/10.1016/j.bios.2022.114233DOI Listing
July 2022
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