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1.
PLoS Genet ; 20(2): e1011152, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38315726

ABSTRACT

Endocytosis and endolysosomal trafficking are essential for almost all aspects of physiological functions of eukaryotic cells. As our understanding on these membrane trafficking events are mostly from studies in yeast and cultured mammalian cells, one challenge is to systematically evaluate the findings from these cell-based studies in multicellular organisms under physiological settings. One potentially valuable in vivo system to address this challenge is the vitellogenic oocyte in Drosophila, which undergoes extensive endocytosis by Yolkless (Yl), a low-density lipoprotein receptor (LDLR), to uptake extracellular lipoproteins into oocytes and package them into a specialized lysosome, the yolk granule, for storage and usage during later development. However, by now there is still a lack of sufficient understanding on the molecular and cellular processes that control yolk granule biogenesis. Here, by creating genome-tagging lines for Yl receptor and analyzing its distribution in vitellogenic oocytes, we observed a close association of different endosomal structures with distinct phosphoinositides and actin cytoskeleton dynamics. We further showed that Rab5 and Rab11, but surprisingly not Rab4 and Rab7, are essential for yolk granules biogenesis. Instead, we uncovered evidence for a potential role of Rab7 in actin regulation and observed a notable overlap of Rab4 and Rab7, two Rab GTPases that have long been proposed to have distinct spatial distribution and functional roles during endolysosomal trafficking. Through a small-scale RNA interference (RNAi) screen on a set of reported Rab5 effectors, we showed that yolk granule biogenesis largely follows the canonical endolysosomal trafficking and maturation processes. Further, the data suggest that the RAVE/V-ATPase complexes function upstream of or in parallel with Rab7, and are involved in earlier stages of endosomal trafficking events. Together, our study provides s novel insights into endolysosomal pathways and establishes vitellogenic oocyte in Drosophila as an excellent in vivo model for dissecting the highly complex membrane trafficking events in metazoan.


Subject(s)
Drosophila , Endosomes , Animals , Drosophila/genetics , Drosophila/metabolism , Endosomes/genetics , Endosomes/metabolism , rab GTP-Binding Proteins/genetics , rab GTP-Binding Proteins/metabolism , Oocytes/metabolism , Lysosomes/genetics , Lysosomes/metabolism , Mammals/metabolism
2.
Nucleic Acids Res ; 52(D1): D1407-D1417, 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-37739405

ABSTRACT

Advances in sequencing and imaging technologies offer a unique opportunity to unravel cell heterogeneity and develop new immunotherapy strategies for cancer research. There is an urgent need for a resource that effectively integrates a vast amount of transcriptomic profiling data to comprehensively explore cancer tissue heterogeneity and the tumor microenvironment. In this context, we developed the Single-cell and Spatially-resolved Cancer Resources (SCAR) database, a combined tumor spatial and single-cell transcriptomic platform, which is freely accessible at http://8.142.154.29/SCAR2023 or http://scaratlas.com. SCAR contains spatial transcriptomic data from 21 tumor tissues and single-cell transcriptomic data from 11 301 352 cells encompassing 395 cancer subtypes and covering a wide variety of tissues, organoids, and cell lines. This resource offers diverse functional modules to address key cancer research questions at multiple levels, including the screening of tumor cell types, metabolic features, cell communication and gene expression patterns within the tumor microenvironment. Moreover, SCAR enables the analysis of biomarker expression patterns and cell developmental trajectories. SCAR also provides a comprehensive analysis of multi-dimensional datasets based on 34 state-of-the-art omics techniques, serving as an essential tool for in-depth mining and understanding of cell heterogeneity and spatial location. The implications of this resource extend to both cancer biology research and cancer immunotherapy development.


Subject(s)
Databases, Factual , Gene Expression Profiling , Neoplasms , Humans , Cell Differentiation , Gene Expression Profiling/methods , Neoplasms/genetics , Neoplasms/pathology , Transcriptome , Tumor Microenvironment , Single-Cell Analysis
3.
Nucleic Acids Res ; 52(D1): D998-D1009, 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-37930842

ABSTRACT

The nervous system is one of the most complicated and enigmatic systems within the animal kingdom. Recently, the emergence and development of spatial transcriptomics (ST) and single-cell RNA sequencing (scRNA-seq) technologies have provided an unprecedented ability to systematically decipher the cellular heterogeneity and spatial locations of the nervous system from multiple unbiased aspects. However, efficiently integrating, presenting and analyzing massive multiomic data remains a huge challenge. Here, we manually collected and comprehensively analyzed high-quality scRNA-seq and ST data from the nervous system, covering 10 679 684 cells. In addition, multi-omic datasets from more than 900 species were included for extensive data mining from an evolutionary perspective. Furthermore, over 100 neurological diseases (e.g. Alzheimer's disease, Parkinson's disease, Down syndrome) were systematically analyzed for high-throughput screening of putative biomarkers. Differential expression patterns across developmental time points, cell types and ST spots were discerned and subsequently subjected to extensive interpretation. To provide researchers with efficient data exploration, we created a new database with interactive interfaces and integrated functions called the Spatiotemporal Cloud Atlas for Neural cells (SCAN), freely accessible at http://47.98.139.124:8799 or http://scanatlas.net. SCAN will benefit the neuroscience research community to better exploit the spatiotemporal atlas of the neural system and promote the development of diagnostic strategies for various neurological disorders.


Subject(s)
Databases, Genetic , Nervous System Diseases , Neurons , Single-Cell Gene Expression Analysis , Animals , Neurons/metabolism , Atlases as Topic , Nervous System Diseases/genetics
4.
Nucleic Acids Res ; 51(D1): D1150-D1159, 2023 01 06.
Article in English | MEDLINE | ID: mdl-36305818

ABSTRACT

It is a challenge to efficiently integrate and present the tremendous amounts of single-cell data generated from multiple tissues of various species. Here, we create a new database named SPEED for single-cell pan-species atlas in the light of ecology and evolution for development and diseases (freely accessible at http://8.142.154.29 or http://speedatlas.net). SPEED is an online platform with 4 data modules, 7 function modules and 2 display modules. The 'Pan' module is applied for the interactive analysis of single cell sequencing datasets from 127 species, and the 'Evo', 'Devo', and 'Diz' modules provide comprehensive analysis of single-cell atlases on 18 evolution datasets, 28 development datasets, and 85 disease datasets. The 'C2C', 'G2G' and 'S2S' modules explore intercellular communications, genetic regulatory networks, and cross-species molecular evolution. The 'sSearch', 'sMarker', 'sUp', and 'sDown' modules allow users to retrieve specific data information, obtain common marker genes for cell types, freely upload, and download single-cell datasets, respectively. Two display modules ('HOME' and 'HELP') offer easier access to the SPEED database with informative statistics and detailed guidelines. All in all, SPEED is an integrated platform for single-cell RNA sequencing (scRNA-seq) and single-cell whole-genome sequencing (scWGS) datasets to assist the deep-mining and understanding of heterogeneity among cells, tissues, and species at multi-levels, angles, and orientations, as well as provide new insights into molecular mechanisms of biological development and pathogenesis.


Subject(s)
Databases, Factual , Single-Cell Analysis , Humans , Animals , Biological Evolution , Plants/genetics , Ecology
5.
PLoS Genet ; 18(7): e1010302, 2022 07.
Article in English | MEDLINE | ID: mdl-35853002

ABSTRACT

Perturbation of huntingtin (HTT)'s physiological function is one postulated pathogenic factor in Huntington's disease (HD). However, little is known how HTT is regulated in vivo. In a proteomic study, we isolated a novel ~40kDa protein as a strong binding partner of Drosophila HTT and demonstrated it was the functional ortholog of HAP40, an HTT associated protein shown recently to modulate HTT's conformation but with unclear physiological and pathologic roles. We showed that in both flies and human cells, HAP40 maintained conserved physical and functional interactions with HTT. Additionally, loss of HAP40 resulted in similar phenotypes as HTT knockout. More strikingly, HAP40 strongly affected HTT's stability, as depletion of HAP40 significantly reduced the levels of endogenous HTT protein while HAP40 overexpression markedly extended its half-life. Conversely, in the absence of HTT, the majority of HAP40 protein were degraded, likely through the proteasome. Further, the affinity between HTT and HAP40 was not significantly affected by polyglutamine expansion in HTT, and contrary to an early report, there were no abnormal accumulations of endogenous HAP40 protein in HD cells from mouse HD models or human patients. Lastly, when tested in Drosophila models of HD, HAP40 partially modulated the neurodegeneration induced by full-length mutant HTT while showed no apparent effect on the toxicity of mutant HTT exon 1 fragment. Together, our study uncovers a conserved mechanism governing the stability and in vivo functions of HTT and demonstrates that HAP40 is a central and positive regulator of endogenous HTT. Further, our results support that mutant HTT is toxic regardless of the presence of its partner HAP40, and implicate HAP40 as a potential modulator of HD pathogenesis through its multiplex effect on HTT's function, stability and the potency of mutant HTT's toxicity.


Subject(s)
Huntingtin Protein , Huntington Disease , Intracellular Signaling Peptides and Proteins , Nuclear Proteins , Animals , Disease Models, Animal , Drosophila/genetics , Drosophila/metabolism , Humans , Huntingtin Protein/genetics , Huntingtin Protein/metabolism , Huntington Disease/genetics , Huntington Disease/metabolism , Huntington Disease/pathology , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/metabolism , Mice , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Proteasome Endopeptidase Complex/genetics , Proteomics
6.
Carcinogenesis ; 45(5): 351-357, 2024 May 19.
Article in English | MEDLINE | ID: mdl-38310539

ABSTRACT

Immune checkpoint inhibitors (ICIs) have become prominent therapies for gastrointestinal cancer (GC). However, it is urgent to screen patients who can benefit from ICIs. Protein patched homolog 1 (PTCH1) is a frequently altered gene in GC. We attempt to explore the association between PTCH1 mutation and immunotherapy efficacy. The Memorial Sloan Kettering Cancer Center (MSKCC) cohort (n = 236) with GC (esophageal, gastric and colorectal cancers) patients receiving ICIs was used for discovery and the Peking University Cancer Hospital (PUCH) GC cohort (n = 92) was used for validation. Overall survival (OS) and tumor mutational burden (TMB) of the PTCH1 mutant-type (PTCH1-MUT) and PTCH1 wild-type (PTCH1-WT) groups were compared. Furthermore, GC data were collected from The Cancer Genome Atlas to assess the potential mechanisms. In the MSKCC cohort, PTCH1-MUT group showed significantly better OS (P = 0.017) and higher TMB. Multivariate analysis showed that PTCH1 mutation was associated with better OS. In the PUCH cohort, PTCH1-MUT group showed significantly longer OS (P = 0.036) and progression-free survival, and higher durable clinical benefit and TMB. Immune cell infiltration analysis revealed that PTCH1-MUT group had significantly higher distributions of CD8 T cells, CD4 T cells, NK cells, mast cells and M1 cells. The PTCH1-MUT group showed significantly higher expression of most immune-related genes. Gene set enrichment analysis showed that the PTCH1-MUT group had enriched INF-γ response, INF-α response, glycolysis and reactive oxygen species pathway gene sets. PTCH1 mutation may represent a potential biomarker for predicting ICIs response in GC. Nevertheless, prospective cohort studies should be performed to further validate our results.


Subject(s)
Biomarkers, Tumor , Gastrointestinal Neoplasms , Immune Checkpoint Inhibitors , Mutation , Patched-1 Receptor , Humans , Patched-1 Receptor/genetics , Immune Checkpoint Inhibitors/therapeutic use , Biomarkers, Tumor/genetics , Female , Gastrointestinal Neoplasms/genetics , Gastrointestinal Neoplasms/drug therapy , Gastrointestinal Neoplasms/pathology , Male , Middle Aged , Aged , Prognosis , Adult
7.
Invest New Drugs ; 42(1): 60-69, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38071684

ABSTRACT

Identifying biomarkers to evaluate the therapeutic effect of immune checkpoint inhibitors (ICIs) is crucial. Regulatory Associated Protein of MTOR Complex 1 (RPTOR), one of the genes in the mTOR pathway, plays a role in regulating tumor progression. However, the connection between RPTOR mutation and the efficacy of ICIs in melanoma remains unclear. The data of ICIs-treated melanoma patients in discovery (n = 384) and validation (n = 320) cohorts were obtained from cBioPortal databases. The genomic data in the two cohorts was used to investigate the connection between RPTOR mutation and immunotherapy efficacy. The underlying mechanisms were explored based on data from the The Cancer Genome Atlas (TCGA)-skin cutaneous melanoma (SKCM) cohort. Compared to melanoma patients with RPTOR wildtype (RPTOR-WT), RPTOR-mutation (RPTOR-Mut) patients achieved prolonged overall survival (OS) in both discovery cohort (median OS of 49.3 months vs. 21.7 months; HR = 0.41, 95% CI: 0.18-0.92; P = 0.026) and validation cohorts (not reached vs. 42.0 months; HR = 0.34, 95% CI: 0.11-1.06; P = 0.049). RPTOR-Mut melanoma patients exhibited a higher objective response rate (ORR) than RPTOR-WT patients in the discovery cohort (55.0% vs. 29.0%, P = 0.022). RPTOR-Mut patients exhibited higher TMB than RPTOR-WT patients in both discovery and validation cohorts (P < 0.001). RPTOR-Mut melanoma patients had an increased number of DNA damage response (DDR) mutations in TCGA-SKCM cohort. Immune cell infiltration analysis suggested that activated CD4 memory T cells were more enriched in RPTOR-Mut tumors. RPTOR-Mut melanoma patients had higher expression levels of immune-related genes than the RPTOR-WT patients. Our results suggest that RPTOR mutation could serve as a predictor of effective immunotherapy for melanoma.


Subject(s)
Melanoma , Skin Neoplasms , Humans , Melanoma/drug therapy , Melanoma/genetics , Regulatory-Associated Protein of mTOR , Skin Neoplasms/drug therapy , Skin Neoplasms/genetics , Immunotherapy , Mutation , Biomarkers, Tumor/genetics
8.
Invest New Drugs ; 42(1): 1-13, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37971628

ABSTRACT

Advances in immune checkpoint inhibitors (ICIs) have enabled more effective treatment for individuals with various types of solid tumors. Given the improved survival benefit and acceptable safety profile of ICIs in advanced gastric cancer, there is plenty of interest in the use of ICIs in the neoadjuvant setting with curative intent. Theoretically, immunoneoadjuvant with ICIs could boost the levels of endogenous tumor antigen present in the tumor to enhance T-cell priming and further enhance systemic immunity. This systemic immune response may improve the detection and elimination of the disseminated micrometastatic tumors beyond the resected tumor, which are sources of postsurgical relapse. Numerous clinical studies have begun to explore the application of ICIs in neoadjuvant treatment of gastric cancer. This article reviews the progress in the use of ICI monotherapy and in combination with alternative therapies for the treatment of gastric cancer to aid in the development of gastric cancer immunoneoadjuvant therapy and improve the overall therapeutic benefit.


Subject(s)
Stomach Neoplasms , Humans , Stomach Neoplasms/drug therapy , Immune Checkpoint Inhibitors/adverse effects , Neoadjuvant Therapy
9.
Cell Biol Toxicol ; 40(1): 11, 2024 02 06.
Article in English | MEDLINE | ID: mdl-38319415

ABSTRACT

Neutrophils play a crucial role in the immune system within tumor microenvironment. At present, numerous studies have explored the changes of neutrophils' automatic killing effect and cellular communication with other immune cells under pathological conditions through single-cell sequencing. However, there remains a lack of definite conclusion about the identification criteria of neutrophil subgroups. Here, we collected tumor and para-carcinoma tissues, pre- and postoperative blood from patients with non-small cell lung cancer (NSCLC), and performed single-cell RNA (scRNA) sequencing to evaluate the distribution of neutrophil subgroups. We have developed a computational method of over expression rate (OER) to evaluate the specificity of neutrophil subgroups, in order to target gene panels with potential clinical application value. In addition, OER was used to evaluate specificity of neutrophil subsets in healthy people and patients with various diseases to further validate the feasibility of this evaluation system. As a result, we found the specificity of Neu_ c1_ IL1B and Neu_ c2_ cxcr4 (low) in postoperative blood has increased, while that of IL-7R + neutrophils has decreased, indicating that these groups of cells possibly differentiated or migrated to other subgroups in the state of lung cancer. In addition, seven gene panels (Neu_c3_CST7, RSAD2_Neu, S100A2/Pabpc1_Neu, ISG15/Ifit3_Neu, CD74_Neu, PTGS2/Actg1_Neu, SPP1_Neu) were high specific in all the four NSCLC-associated samples, meaning that changes in the percentage of these cell populations would have a high degree of confidence in assessing changes of disease status. In conclusion, combined consideration of the distribution characteristics of neutrophil subgroups could help evaluate the diagnosis and prognosis of NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Tumor Microenvironment , Neutrophils , Lung
10.
Phys Chem Chem Phys ; 26(24): 17155-17170, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38847473

ABSTRACT

Metal-ion doping and halogen substitution have been largely applied to tune the bandgap of bismuth oxybromide (BiOBr) to upgrade its photodegradation capacity. In this work, the adsorption capacity and photocatalytic behavior of solvothermally synthesized BiOBr photocatalysts can be optimized via the synergistic effect of Y3+- and I--doping. After an adsorption reaction in the dark and exposure for another 80 min to visible light, pure BiOBr can remove 46.5% of Congo red (CR) from water with an initial CR concentration of 50 mg L-1. Meanwhile, Bi0.8Y0.20OBr0.97I0.03, the co-doped catalyst, displays total degradation rates exceeding 98% and 92% with CR dosages of 50 and 100 mg L-1, respectively, demonstrating a doubled degradation capacity. With the co-doping solution, the negative charges on the catalysts reduce, more oxygen vacancies are generated, the bandgap remarkably narrows, and the photoabsorption range broadens for derivation of photoinduced electron-hole pairs. The mechanism for optimized photodegradation behavior and dramatically increased adsorption capacity are discussed based on analyses of the structural evolution, surface properties including the chemical state and surface charge, electrochemical performance and the yield/type of photogenerated species. Density functional theory (DFT) simulations were conducted to investigate the structural state, density of states (DOS) and electrostatic potential.

11.
Nucleic Acids Res ; 50(D1): D934-D942, 2022 01 07.
Article in English | MEDLINE | ID: mdl-34634807

ABSTRACT

Viral infectious diseases are a devastating and continuing threat to human and animal health. Receptor binding is the key step for viral entry into host cells. Therefore, recognizing viral receptors is fundamental for understanding the potential tissue tropism or host range of these pathogens. The rapid advancement of single-cell RNA sequencing (scRNA-seq) technology has paved the way for studying the expression of viral receptors in different tissues of animal species at single-cell resolution, resulting in huge scRNA-seq datasets. However, effectively integrating or sharing these datasets among the research community is challenging, especially for laboratory scientists. In this study, we manually curated up-to-date datasets generated in animal scRNA-seq studies, analyzed them using a unified processing pipeline, and comprehensively annotated 107 viral receptors in 142 viruses and obtained accurate expression signatures in 2 100 962 cells from 47 animal species. Thus, the VThunter database provides a user-friendly interface for the research community to explore the expression signatures of viral receptors. VThunter offers an informative and convenient resource for scientists to better understand the interactions between viral receptors and animal viruses and to assess viral pathogenesis and transmission in species. Database URL: https://db.cngb.org/VThunter/.


Subject(s)
Databases, Factual , Genome, Viral , Host-Pathogen Interactions/genetics , Receptors, Virus/genetics , Software , Virus Diseases/genetics , Viruses/genetics , Animals , Binding Sites , Datasets as Topic , Gene Expression Regulation , High-Throughput Nucleotide Sequencing , Humans , Internet , Molecular Sequence Annotation , Protein Binding , Receptors, Virus/classification , Receptors, Virus/metabolism , Signal Transduction , Single-Cell Analysis , Virus Diseases/metabolism , Virus Diseases/transmission , Virus Diseases/virology , Viruses/classification , Viruses/metabolism , Viruses/pathogenicity
12.
Mol Genet Genomics ; 298(4): 823-836, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37059908

ABSTRACT

Coronavirus 2019 (COVID-19) is a complex disease that affects billions of people worldwide. Currently, effective etiological treatment of COVID-19 is still lacking; COVID-19 also causes damages to various organs that affects therapeutics and mortality of the patients. Surveillance of the treatment responses and organ injury assessment of COVID-19 patients are of high clinical value. In this study, we investigated the characteristic fragmentation patterns and explored the potential in tissue injury assessment of plasma cell-free DNA in COVID-19 patients. Through recruitment of 37 COVID-19 patients, 32 controls and analysis of 208 blood samples upon diagnosis and during treatment, we report gross abnormalities in cfDNA of COVID-19 patients, including elevated GC content, altered molecule size and end motif patterns. More importantly, such cfDNA fragmentation characteristics reflect patient-specific physiological changes during treatment. Further analysis on cfDNA tissue-of-origin tracing reveals frequent tissue injuries in COVID-19 patients, which is supported by clinical diagnoses. Hence, our work demonstrates and extends the translational merit of cfDNA fragmentation pattern as valuable analyte for effective treatment monitoring, as well as tissue injury assessment in COVID-19.


Subject(s)
COVID-19 , Cell-Free Nucleic Acids , Humans , COVID-19/diagnosis , Cell-Free Nucleic Acids/genetics
13.
Invest New Drugs ; 41(6): 861-869, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37864727

ABSTRACT

Globally, gastrointestinal cancer is the most widespread neoplastic disease and the primary contributor to cancer-associated fatalities. Gastrointestinal signet ring cell carcinoma (SRCC) exhibits unique distinguishing features in several aspects when compared to adenocarcinomas (ACs). The scarcity of signet ring cell carcinoma has resulted in a heightened significance of related clinical and molecular investigations. However, a comprehensive and systematic review of the clinical, molecular, therapeutic, and research aspects of this disease is currently absent. This review provides an overview of the latest developments in our understanding of the clinical and molecular features of gastrointestinal signet ring cell carcinoma (SRCC). Additionally, we have compiled a list of potential therapeutic targets or biomarkers, as well as an examination of the current treatment options and the possible mechanisms of formation.


Subject(s)
Adenocarcinoma , Carcinoma, Signet Ring Cell , Gastrointestinal Neoplasms , Humans , Gastrointestinal Neoplasms/therapy , Carcinoma, Signet Ring Cell/diagnosis , Carcinoma, Signet Ring Cell/pathology , Biomarkers
14.
Langmuir ; 39(17): 6151-6159, 2023 May 02.
Article in English | MEDLINE | ID: mdl-37076449

ABSTRACT

Human-machine interactions, medical monitoring, and flexible robots stimulate interest in hydrogel sensing devices. However, developing hydrogel sensors with multifunctions such as good mechanics, electroconductivity, resistance to solvent volatility as well as freezing, self-adhesion, and independence on external power supply remains a challenge. In the work, a poly(acrylic acid-N-isopropylacrylamide) P(AA-NIPAm) organic hydrogel loading LiCl is prepared by ultraviolet cross-linking in ethylene glycol/H2O. The organic hydrogel exhibits favorable mechanical properties such as an elongation of break at 700% and a breaking strength of 20 KPa, can adhere to various substrates, and resists frost and solvent volatility. Especially, it possesses an excellent conductivity of 8.51 S/m. The organic hydrogel shows wide strain sensitivity based on resistance change, and the gauge factor reaches 5.84 in the range of 300-700%. It has short responsive and recuperative time and is still stable within 1000 rounds. Moreover, the organic hydrogel is also assembled into a self-powered device in which the open-circuit voltage is 0.74 V. The device can transform external stimuli such as stretching or compressing into the output current change, so it detects human motion effectively in real time. The work provides a perspective for electrical sensing engineering.

15.
Cell Biol Toxicol ; 39(5): 2431-2435, 2023 10.
Article in English | MEDLINE | ID: mdl-36169743

ABSTRACT

Horseshoe bats (Rhinolophus sinicus) might help maintain coronaviruses severely affecting human health, such as severe acute respiratory syndrome coronavirus (SARS-CoV). Bats may be more tolerant of viral infection than other mammals due to their unique immune system, but the exact mechanism remains to be fully explored. During the coronavirus disease 2019 (COVID-19) pandemic, multiple animal species were diseased by coronavirus infection, especially in the respiratory system. Herein, a comparative analysis with single nucleus transcriptomic data of the lungs across four species, including horseshoe bat, cat, tiger, and pangolin, were conducted. The distribution of entry factors for twenty-eight respiratory viruses was characterized for the four species. Our findings might increase our understanding of the immune background of horseshoe bats.


Subject(s)
COVID-19 , Chiroptera , Tigers , Animals , Humans , Pangolins , Lung
16.
Int Wound J ; 21(3): e14457, 2023 Nov 01.
Article in English | MEDLINE | ID: mdl-37909266

ABSTRACT

We aimed to quantitatively and systematically elucidate the rationality of the examined variables as independent risk factors for sternal wound infection. We searched databases to screen studies, ascertained the variables to be analysed, extracted the data and applied meta-analysis to each qualified variable. Odds ratios and mean differences were considered to be the effect sizes for binary and continuous variables, respectively. A random-effects model was used for these procedures. The source of heterogeneity was evaluated using a meta-regression. Publication bias was tested by funnel plot and Egger's test, the significant results of which were then calculated using trim and fill analysis. We used a sensitivity analysis and bubble chart to describe their robustness. After screening all variables in the eligible literature, we excluded 55 because only one or no research found them significant after multivariate analysis, leaving 33 variables for synthesis. Two binary variables (age over 65 years, NYHA class >2) and a continuous variable (preoperative stay) were not significant after the meta-analysis. The most robust independent risk factors in our study were diabetes mellitus, obesity, use of bilateral internal thoracic arteries, chronic obstructive pulmonary disease, prolonged surgery time, prolonged ventilation and critical preoperative state, followed by congestive heart failure, atrial fibrillation, renal insufficiency, stroke, peripheral vascular disease and use of an intra-aortic balloon pump. Relatively low-risk factors were emergent/urgent surgery, smoking, myocardial infarction, combined surgery and coronary artery bypass grafting. Sternal wound infection after open-heart surgery is a multifactorial disease. The detected risk factors significantly affected the wound healing process, but some were different in strength. Anything that affects wound healing and antibacterial ability, such as lack of oxygen, local haemodynamic disorders, malnutrition condition and compromised immune system will increase the risk, and this reminds us of comprehensive treatment during the perioperative period.

17.
Anticancer Drugs ; 33(10): 1186-1190, 2022 11 01.
Article in English | MEDLINE | ID: mdl-35946569

ABSTRACT

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have significantly improved response in all stages of patients with EGFR positive mutations in nonsmall cell lung cancer. However, the primary resistance mechanism of EGFR-TKIs has not been thoroughly revealed. Here, we described a case of a 64-year-old male with lung adenocarcinoma presented primary resistance on osimertinib combined with bevacizumab and platinum-based chemotherapy, next-generation sequencing revealed EGFR exon 21 L858R mutation and MET gene amplification. Afterward, savolitinib monotherapy was started until now, and the treatment was temporarily successful, the last follow-up clinical evaluation was near complete response, the progression-free survival has over 7 months. Our case highlights that EGFR-TKIs may be not the optimal choice for lung adenocarcinoma with primary EGFR -sensitive mutation with MET amplification simultaneously, whereas MET inhibitor alone may be an effective treatment option. In clinical practice, we should fully consider the possibility of primary resistance in EGFR-TKIs administration.


Subject(s)
Adenocarcinoma of Lung , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Acrylamides , Adenocarcinoma of Lung/drug therapy , Aniline Compounds/therapeutic use , Bevacizumab/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , ErbB Receptors/genetics , Humans , Indoles , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , Middle Aged , Mutation , Protein Kinase Inhibitors/pharmacology , Pyrazines , Pyrimidines , Triazines
18.
BMC Surg ; 22(1): 257, 2022 Jul 04.
Article in English | MEDLINE | ID: mdl-35787287

ABSTRACT

BACKGROUND: Existing approaches for treating elbow fractures include lateral, medial, anterior and posterior approaches, though the anterior approach is often not chosen by surgeons to avoid damage to important nerves and blood vessels. However, the anterior approach has unique advantages. The purpose of this study was to report outcomes of 38 patients with coronal plane elbow fractures treated through the anterior approach. METHODS: We retrospectively analyzed 38 cases of coronal plane elbow fracture treated through an anterior approach at our institution between March 2015 and July 2019. The length of the surgical incision, operation time, and postoperative complications were recorded. The range of flexion, extension, and rotation of the affected elbow and the healthy elbow were collected at follow-up. Functional outcomes were evaluated using the Mayo Elbow Function Score (MEPS). RESULTS: All 38 patients were followed up for a mean of 21.26 months (range 12-36 months). Intraoperatively, the mean surgical incision length was 8 ± 2 cm and the mean operative time was 123 ± 59 min. At the final follow-up, solid osseous union was confirmed for all coronal plane elbow fractures. The mean elbow flexion arc was 129 ± 7°, and the extension arc was 9 ± 6°. The mean pronation arc was 83 ± 3°, and the supination arc was 80 ± 3°. The mean MEPS was 90 ± 8 points, with 18 excellent cases and 20 cases of excellent and good results, respectively. In 31 cases, there was no significant difference in elbow extension, flexion, or pronation between the single-fracture and healthy elbows (P > 0.05), though the arc of supination was slightly worse than that of the healthy elbow (P < 0.05). VAS pain scores before the operation, at three months after the operation, and during follow-up were compared, and pain was significantly reduced after treatment (P < 0.05). Two patients experienced transient postoperative median nerve paralysis, from which they recovered within three months. One patient had mild heterotopic ossification and was not treated because it did not affect the function of the elbow joint. All patients returned to work and were satisfied with the treatment. CONCLUSION: The anterior approach has the benefits of simplicity, safety, minimal invasiveness, excellent exposure, and satisfactory prognosis for coronal plane elbow fracture.


Subject(s)
Elbow Joint , Fractures, Bone , Surgical Wound , Elbow Joint/surgery , Humans , Pain , Retrospective Studies
19.
BMC Surg ; 22(1): 77, 2022 Mar 03.
Article in English | MEDLINE | ID: mdl-35241038

ABSTRACT

BACKGROUND: Humeral nonunion with significant bone loss or shortening is uncommon and poses a complex clinical problem. We present a case of humeral nonunion with a large segmental bone defect treated with the distraction osteogenesis technique and remedy the radial nerve palsy produced during distraction osteogenesis by forearm tendon transfers. The reconstruction of upper limb function was achieved with satisfactory results. This case provides a referenceable alternative method for repairing large segmental bone defects due to complex nonunion of the upper extremity, as well as a remedy in the unfortunate event of radial nerve palsy, providing a reference and lessons learned for the treatment of similar cases and the management of possible complications. CASE PRESENTATION: A 31-year-old male patient experienced 9 years of hypertrophic nonunion due to an unreliable internal fixation. The radiographs showed the absence of bone bridging between the two fragments, loosening of the screws, and extensive osteolysis around the internal screws. The patient was treated with distraction osteogenesis. At the end of the distraction period, the patient unfortunately developed right radial nerve paresis, which was salvaged by forearm tendon transplantation, and finally reconstructed hand function and achieved bone union of the humerus. CONCLUSION: Distraction osteogenesis, although not a panacea for all humeral nonunions with significant segmental bone loss, does offer a viable salvage procedure in this unusual and often complex clinical problem. When irreversible radial nerve palsy occurs during distraction, forearm tendon transfers can have a good clinical effect.


Subject(s)
Fractures, Ununited , Humeral Fractures , Osteogenesis, Distraction , Adult , Fracture Fixation, Internal/methods , Fractures, Ununited/complications , Fractures, Ununited/diagnostic imaging , Fractures, Ununited/surgery , Humans , Humeral Fractures/complications , Humeral Fractures/diagnostic imaging , Humeral Fractures/surgery , Humerus/surgery , Male , Osteogenesis, Distraction/methods , Radiography
20.
J Environ Manage ; 317: 115438, 2022 Sep 01.
Article in English | MEDLINE | ID: mdl-35653844

ABSTRACT

Health inequalities are globally widespread due to the regional socioeconomic inequalities. Myocardial infarction (MI) is a leading health problem causing deaths worldwide. Yet medical services for it are often inequitably distributed by region. Moreover, studies concerning MI's potential spatial risk factors generally suffer from difficulties in focusing on too few factors, inappropriate models, and coarse spatial grain of data. To address these issues, this paper integrates registered 1098 MI cases and urban multi-source spatio-temporal big data, and spatially analyses the risk factors for MI severity by applying an advanced interpretable model, the random forest algorithm (RFA)-based SHapley Additive exPlanations (SHAP) model. In addition, a community-scale model between spatio-temporal risk factors and MI cases is constructed to predict the MI severity of all communities in Wuhan, China. The results suggest that those risk factors (i.e., age of patients, medical quality, temperature changes, air pollution and urban habitat) affect the MI severity at the community scale. We found that Wuhan residents in the downtown area are at risk for high MI severity, and the surrounding suburb areas show a donut-shape pattern of risk for medium-to-high MI severity. These patterns draw our attention to the impact of spatial environmental risk factors on MI severity. Thus, this paper provides three recommendations for urban planning to reduce the risk and mortality from severe MI in the aspect of policy implication.


Subject(s)
Air Pollution , Myocardial Infarction , Air Pollution/analysis , China , Cities , Humans , Myocardial Infarction/epidemiology , Risk Factors
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