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1.
Nat Commun ; 15(1): 3674, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38697956
2.
Plant Divers ; 46(3): 283-293, 2024 May.
Article in English | MEDLINE | ID: mdl-38798729

ABSTRACT

The effect of evolutionary history on wood density variation may play an important role in shaping variation in wood density, but this has largely not been tested. Using a comprehensive global dataset including 27,297 measurements of wood density from 2621 tree species worldwide, we test the hypothesis that the legacy of evolutionary history plays an important role in driving the variation of wood density among tree species. We assessed phylogenetic signal in different taxonomic (e.g., angiosperms and gymnosperms) and ecological (e.g., tropical, temperate, and boreal) groups of tree species, explored the biogeographical and phylogenetic patterns of wood density, and quantified the relative importance of current environmental factors (e.g., climatic and soil variables) and evolutionary history (i.e., phylogenetic relatedness among species and lineages) in driving global wood density variation. We found that wood density displayed a significant phylogenetic signal. Wood density differed among different biomes and climatic zones, with higher mean values of wood density in relatively drier regions (highest in subtropical desert). Our study revealed that at a global scale, for angiosperms and gymnosperms combined, phylogeny and species (representing the variance explained by taxonomy and not direct explained by long-term evolution process) explained 84.3% and 7.7% of total wood density variation, respectively, whereas current environment explained 2.7% of total wood density variation when phylogeny and species were taken into account. When angiosperms and gymnosperms were considered separately, the three proportions of explained variation are, respectively, 84.2%, 7.5% and 6.7% for angiosperms, and 45.7%, 21.3% and 18.6% for gymnosperms. Our study shows that evolutionary history outpaced current environmental factors in shaping global variation in wood density.

3.
Bioact Mater ; 39: 135-146, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38783928

ABSTRACT

Iron is considered as an attractive alternative material for bioresorbable scaffolds (BRS). The sirolimus eluting iron bioresorbable scaffold (IBS), developed by Biotyx Medical (Shenzhen, China), is the only iron-based BRS with an ultrathin-wall design. The study aims to investigate the long-term efficacy, safety, biocompatibility, and lumen changes during the biodegradation process of the IBS in a porcine model. A total of 90 IBSs and 70 cobalt-chromium everolimus eluting stents (EES) were randomly implanted into nonatherosclerotic coronary artery of healthy mini swine. The multimodality assessments including coronary angiography, optical coherence tomography, micro-computed tomography, magnetic resonance imaging, real-time polymerase chain reaction (PCR), and histopathological evaluations, were performed at different time points. There was no statistical difference in area stenosis between IBS group and EES group at 6 months, 1year, 2 years and 5 years. Although the scaffolded vessels narrowed at 9 months, expansive remodeling with increased mean lumen area was found at 3 and 5 years. The IBS struts remained intact at 6 months, and the corrosion was detectable at 9 months. At 5 years, the iron struts were completely degraded and absorbed in situ, without in-scaffold restenosis or thrombosis, lumen collapse, aneurysm formation, and chronic inflammation. No local or systemic toxicity and abnormal histopathologic manifestation were found in all experiments. Results from real-time PCR indicated that no sign of iron overload was reported in scaffolded segments. Therefore, the IBS shows comparable efficacy, safety, and biocompatibility with EES, and late lumen enlargement is considered as a unique feature in the IBS-implanted vessels.

4.
Ann Bot ; 2024 May 25.
Article in English | MEDLINE | ID: mdl-38795069

ABSTRACT

BACKGROUND AND AIMS: Latitudinal diversity gradients have been intimately linked to the tropical niche conservatism hypothesis, which posits that there has been a strong filter due to the challenges faced by ancestral tropical lineages to adapt to low temperatures and colonize extra-tropical regions. In liverworts, species richness is higher towards the tropics, but the centers of diversity of the basal lineages are distributed across extra-tropical regions, pointing to the colonization of tropical regions by phylogenetically clustered assemblages of species of temperate origin. Here, we test this hypothesis through analyses on the relationship between macroclimatic variation and phylogenetic diversity in Chinese liverworts. METHODS: Phylogenetic diversity metrics and their standardized effect sizes for liverworts in each of the 28 regional floras at the province level in China were related to latitude and six climate variables using regression analysis. We conducted variation partitioning analyses to determine the relative importance of each group of climatic variables. KEY RESULTS: We find that the number of species decreases with latitude, whereas phylogenetic diversity shows the reverse pattern, and that phylogenetic diversity is more strongly correlated with temperature-related variables, compared with precipitation-related variables. CONCLUSIONS: We interpret the opposite patterns observed in phylogenetic diversity and species richness in terms of a more recent origin of tropical diversity coupled with higher extinctions in temperate regions.

6.
Plant Divers ; 46(2): 149-157, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38807907

ABSTRACT

Endemism of lineages lies at the core of understanding variation in community composition among geographic regions because it reflects how speciation, extinction, and dispersal have influenced current distributions. Here, we investigated geographic patterns and ecological drivers of taxonomic and phylogenetic endemism of angiosperm genera across the world. We identify centers of paleo-endemism and neo-endemism of angiosperm genera, and show that they are mostly located in the Southern Hemisphere in tropical and subtropical regions, particularly in Asia and Australia. Different categories of phylogenetic endemism centers can be differentiated using current climate conditions. Current climate, historical climate change, and geographic variables together explained ∼80% of global variation in taxonomic and phylogenetic endemism, while 42-46%, 1%, and 15% were independently explained by these three types of variables, respectively. Thus our findings show that past climate change, current climate, and geography act together in shaping endemism, which are consistent with the findings of previous studies that higher temperature and topographic heterogeneity promote endemism. Our study showed that many centers of phylogenetic endemism of angiosperms, including regions in Amazonia, Venezuela, and west-central tropical Africa that have not previously been identified as biodiversity hotspots, are missed by taxon-based measures of endemism, indicating the importance of including evolutionary history in biodiversity assessment.

7.
Int J Biol Sci ; 20(7): 2727-2747, 2024.
Article in English | MEDLINE | ID: mdl-38725857

ABSTRACT

Phenotypic switching (from contractile to synthetic) of vascular smooth muscle cells (VSMCs) is essential in the progression of atherosclerosis. The damaged endothelium in the atherosclerotic artery exposes VSMCs to increased interstitial fluid shear stress (IFSS). However, the precise mechanisms by which increased IFSS influences VSMCs phenotypic switching are unrevealed. Here, we employed advanced numerical simulations to calculate IFSS values accurately based on parameters acquired from patient samples. We then carefully investigated the phenotypic switching and extracellular vesicles (EVs) secretion of VSMCs under various IFSS conditions. By employing a comprehensive set of approaches, we found that VSMCs exhibited synthetic phenotype upon atherosclerotic IFSS. This synthetic phenotype is the upstream regulator for the enhanced secretion of pro-calcified EVs. Mechanistically, as a mechanotransducer, the epidermal growth factor receptor (EGFR) initiates the flow-based mechanical cues to MAPK signaling pathway, facilitating the nuclear accumulation of the transcription factor krüppel-like factor 5 (KLF5). Furthermore, pharmacological inhibiting either EGFR or MAPK signaling pathway blocks the nuclear accumulation of KLF5 and finally results in the maintenance of contractile VSMCs even under increased IFSS stimulation. Collectively, targeting this signaling pathway holds potential as a novel therapeutic strategy to inhibit VSMCs phenotypic switching and mitigate the progression of atherosclerosis.


Subject(s)
ErbB Receptors , Extracellular Vesicles , Kruppel-Like Transcription Factors , Muscle, Smooth, Vascular , Myocytes, Smooth Muscle , Stress, Mechanical , Extracellular Vesicles/metabolism , ErbB Receptors/metabolism , Kruppel-Like Transcription Factors/metabolism , Kruppel-Like Transcription Factors/genetics , Humans , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/metabolism , Extracellular Fluid/metabolism , Phenotype , Animals , Atherosclerosis/metabolism , MAP Kinase Signaling System , Signal Transduction
8.
Front Med (Lausanne) ; 11: 1341015, 2024.
Article in English | MEDLINE | ID: mdl-38751985

ABSTRACT

Background: Hemorrhagic fever with renal syndrome (HFRS) is a natural epidemic disease that can be caused by the Hantaan virus (HTNV). Malaria is caused by plasmodium and can be transmitted by a mosquito bite. The similar manifestations shared by these disorders pose a challenge for clinicians in differential diagnosis, in particular, coupled with a false-positive serological test. Case presentation: A 46-year-old man was admitted for fever and chills for over 10 days and was suspected of being co-infected with HFRS and malaria due to a history of travel to malaria-endemic areas and a positive HTNV-immunoglobulin M (IgM) test. Although leukocytosis, thrombocytopenia, renal injury, lymphocytosis, overexpression of interleukin-6, and procalcitonin were observed during the hospitalization, the hypotensive, oliguria, and polyuria phases of the HFRS course were not observed. Instead, typical symptoms of malaria were found, including a progressive decrease in erythrocytes and hemoglobin levels with signs of anemia. Furthermore, because the patient had no history of exposure to HFRS endemic areas, exposure to an HTNV-infected rodent, or a positive HTNV-IgG test, and false serological tests of IgM can be caused by various factors, the HFRS coinfection with malaria was ruled out. Conclusion: Misdiagnosis can be easily induced by a false serological test, in particular the IgM test which can be influenced by various factors. A combination of health history, epidemiology, physical examination, precise application of specific examinations involving tests of conventional laboratory parameters as well as well-accepted methods such as the immunochromatographic (ICG) test, real-time reverse transcription-polymerase chain reaction (PCR), and Western blot (WB), and acquaintance with disorders with similar manifestations will contribute to the precise diagnosis in clinical treatment.

9.
iScience ; 27(5): 109578, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38638573

ABSTRACT

In this study, a method was developed to create oxygen vacancies in Cu2O/TiO2 heterojunctions. By varying the amounts of ethylenediaminetetraacetic acid (EDTA), sodium citrate, and copper acetate, Cu2O/TiO2 with different Cu ratios were synthesized. Tests on CO2 photocatalytic reduction revealed that Cu2O/TiO2's performance is influenced by Cu content. The ideal Cu mass fraction in Cu2O/TiO2, determined by inductively coupled plasma (ICP), is between 0.075% and 0.55%, with the highest CO yield being 10.22 µmol g-1 h-1, significantly surpassing pure TiO2. High-resolution transmission electron microscopy and electron paramagnetic resonance studies showed optimal oxygen vacancy in the most effective heterojunction. Density functional theory (DFT) calculations indicated a 0.088 eV lower energy barrier for ∗CO2 to ∗COOH conversion in Cu2O/TiO2 with oxygen vacancy compared to TiO2, suggesting that oxygen vacancies enhance photocatalytic activity.

10.
Zhongguo Gu Shang ; 37(2): 153-8, 2024 Feb 25.
Article in Chinese | MEDLINE | ID: mdl-38425066

ABSTRACT

OBJECTIVE: To explore the potential value of three-dimensional fast spin echo(3D-SPACE) combined with multilayer spiral CT (MSCT) in the diagnosis of knee cruciate ligament injury, to provide a new direction for the optimization of subsequent clinical diagnosis. METHODS: A total of 120 patients with knee cruciate ligament injury were treated from April 2020 to April 2021, aged from 21 to 68 with an average of(41.52±4.13) years old. For all patients, separate MSCT scanner scans, 3D-SPACE sequence scans alone and 3D-SPACE sequence combined with MSCT scans were used. The injury and classification of the anterior and posterior cruciate ligament of the knee were compared, the length of the anterior-medial bundle and posterolateral bundle and its angle of the knee with the horizontal plane were observed, the diagnostic value of 3 diagnostic methods in knee cruciate ligament injury were determined. RESULTS: There was no significant difference between the 3D-SPACE sequence scan alone and the MSCT test alone on the total diagnostic rate and grading total diagnostic rate(P>0.05). The total diagnostic rate and grading total diagnostic rate of 3D-SPACE scan combined with MSCT were significantly higher than those of 3D-SPACE scan or MSCT alone(P<0.05). The 3D-SPACE sequence scan alone and the MSCT detection alone had no significant difference in the measurement values related to the anterior and posterior cruciate ligaments of the knee joint(P>0.05). 3D-SPACE sequence scanning combined with MSCT detection on the knee joint anterior and posterior cruciate ligament related measurements were significantly higher than the 3D-SPACE sequence scan or MSCT detection alone(P<0.05). The area under the ROC curve estimated by 3D-SPACE sequence scanning combined with MSCT was 0.960, which was significantly higher than that of 3D-SPACE sequence scanning and MSCT alone evaluating the area under the ROC curve line of 0.756 and 0.795. The combined 3D-SPACE sequence scanning and 3D-SPACE sequence scanning MSCT analysis and prediction models were statistically different(Z=2.236, P<0.05), and MSCT alone and 3D-SPACE sequence scanning combined with MSCT analysis and prediction models were statistically different(Z=2.653, P<0.05). CONCLUSION: The application of 3D-SPACE sequence combined with MSCT scanning for knee cruciate ligament injury can improve the diagnosis rate of patients with knee cruciate ligament injury.It can be used as a diagnostic tool for patients with knee cruciate ligament injury and is worthy of clinical application.


Subject(s)
Anterior Cruciate Ligament Injuries , Knee Injuries , Posterior Cruciate Ligament , Soft Tissue Injuries , Humans , Adult , Middle Aged , Magnetic Resonance Imaging/methods , Arthroscopy , Knee Injuries/diagnostic imaging , Knee Joint/diagnostic imaging , Posterior Cruciate Ligament/injuries , Tomography, Spiral Computed , Anterior Cruciate Ligament Injuries/diagnostic imaging
11.
Heliyon ; 10(5): e26618, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38455539

ABSTRACT

Background: Coinfection poses a persistent threat to global public health due to its severe effect on individual-level infection risk and disease outcome. Coinfection of SARS-CoV2 with one or more pathogens has been documented. Nevertheless, this virus co-infected with the Hantaan virus (HTNV) is rarely reported. Case summary: Here, we presented three cases of HTNV complicated with SARS-CoV2 infection. Not only the conditions including general clinical manifestations, immune and inflammation parameters fluctuation presented in the single infection of HTNV or SARS-CoV2 can be found, but also the unexpected manifestations have attracted our attention that presented as more symptoms of HTNV infection including exudative changes in both lungs and an amount of bilateral pleural effusion as well as bilateral kidney enlargement rather than typical viral pneumonia in SARS-CoV2 infection. Fortunately, the conditions of patients gradually return to normal which is beneficial from the antiviral treatment, hemodialysis, and various supportive therapies including anti-inflammation, liver and gastric mucosa protection. Conclusion: Unexpected manifestations of coinfection patients present herein may be associated with multiple factors including virus load, competition or antagonism among antigens, and the susceptibility of target cells to the various pathogens, even though the pathogenesis of HTNV and SARS-CoV2 remains to be elucidated. Given that these two viruses have posed a profound influence on the socioeconomic, healthcare system worldwide, and the threat of coinfection to public health, it is warranted for clinicians, public health authorities, and infectious disease researchers to have a high index of consideration for patients co-infected with HTNV and SARS-CoV2.

12.
Mol Med Rep ; 29(4)2024 Apr.
Article in English | MEDLINE | ID: mdl-38426568

ABSTRACT

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that two pairs of data panels featured in Figs. 2E and 6D, portraying the results from cell invasion and migration assay experiments, appeared to contain overlapping sections, such that data which were intended to show the results from differently performed experiments had apparently been derived from a smaller number of original sources. The authors were able to re­examine their original data (which was also presented to the Editorial Office), and realized that errors has been made in the compilation of Fig. 2. The proposed revised version of Fig. 2, now showing the results from the 'field 1' view of the data, is shown on the next page. Note that these errors did not significantly affect either the results or the conclusions reported in this paper,.All the authors agree to the publication of this Corrigendum, and are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to correct this error; furthermore, they apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 25: 71, 2022; DOI: 10.3892/mmr.2022.12587].

13.
Sci Rep ; 14(1): 5344, 2024 03 04.
Article in English | MEDLINE | ID: mdl-38438458

ABSTRACT

Chronic rotator cuff injuries (CRCIs) still present a great challenge for orthopaedics surgeons. Many new therapeutic strategies are developed to facilitate repair and improve the healing process. However, there is no reliable animal model for chronic rotator cuff injury research. To present a new valuable rat model for future chronic rotator cuff injuries (CRCIs) repair studies, and describe the changes of CRCIs on the perspectives of histology, behavior and MRI. Sixty male Wistar rats were enrolled and underwent surgery of the left shoulder joint for persistent subacromial impingement. They were randomly divided into experimental group (n = 30, a 3D printed PEEK implant shuttled into the lower surface of the acromion) and sham operation group (n = 30, insert the same implant, but remove it immediately). Analyses of histology, behavior, MRI and inflammatory pain-related genes expression profiles were performed to evaluate the changes of CRCIs. After 2-weeks running, the rats in the experimental group exhibited compensatory gait patterns to protect the injured forelimb from loading after 2-weeks running. After 8-weeks running, the rats in the experimental group showed obvious CRCIs pathological changes: (1) acromion bone hyperplasia and thickening of the cortical bone; (2) supraspinatus muscle tendon of the humeral head: the bursal-side tendon was torn and layered with disordered structure, forming obvious gaps; the humeral-side tendon is partially broken, and has a neatly arranged collagen. Partial fat infiltration is found. The coronal T2-weighted images showed that abnormal tendon-to-bone junctions of the supraspinatus tendon. The signal intensity and continuity were destroyed with contracted tendon. At the nighttime, compared with the sham operation group, the expression level of IL-1ß and COX-2 increased significantly (P = 0063, 0.0005) in the experimental group. The expression of COX-2 in experimental group is up-regulated about 1.5 times than that of daytime (P = 0.0011), but the expression of IL-1ß, TNF-a, and NGF are all down-regulated (P = 0.0146, 0.0232, 0.0161). This novel rat model of chronic rotator cuff injuries has the similar characteristics with that of human shoulders. And it supplies a cost-effective, reliable animal model for advanced tissue engineered strategies and future therapeutic strategies.


Subject(s)
Rotator Cuff Injuries , Humans , Rats , Animals , Male , Rotator Cuff Injuries/diagnostic imaging , Rats, Wistar , Cyclooxygenase 2 , Rotator Cuff/diagnostic imaging , Tendons , Interleukin-1beta
14.
Nat Commun ; 15(1): 1079, 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38316752

ABSTRACT

The tendency of species to retain ancestral ecological distributions (phylogenetic niche conservatism) is thought to influence which species from a species pool can persist in a particular environment. Thus, investigating the relationships between measures of phylogenetic structure and environmental variables at a global scale can help understand the variation in species richness and phylogenetic structure in biological assemblages across the world. Here, we analyze a comprehensive data set including 341,846 species in 391 angiosperm floras worldwide to explore the relationships between measures of phylogenetic structure and environmental variables for angiosperms in regional floras across the world and for each of individual continental (biogeographic) regions. We find that the global phylogenetic structure of angiosperms shows clear and meaningful relationships with environmental factors. Current climatic variables have the highest predictive power, especially on phylogenetic metrics reflecting recent evolutionary relationships that are also related to current environmental heterogeneity, presumably because this favors plant speciation in various ways. We also find evidence that past climatic conditions, and particularly refugial conditions, play an important role in determining the phylogenetic structure of regional floras. The relationships between environmental conditions and phylogenetic metrics differ between continents, reflecting the different evolutionary histories of their floras.


Subject(s)
Magnoliopsida , Phylogeny , Magnoliopsida/genetics , Biological Evolution , Plants , Ecosystem
15.
Viruses ; 16(1)2024 01 22.
Article in English | MEDLINE | ID: mdl-38275973

ABSTRACT

(1) Background: Avian influenza has attracted widespread attention because of its severe effect on the poultry industry and potential threat to human health. The H9N2 subtype of avian influenza viruses was the most prevalent in chickens, and there are several commercial vaccines available for the prevention of the H9N2 subtype of avian influenza viruses. However, due to the prompt antigenic drift and antigenic shift of influenza viruses, outbreaks of H9N2 viruses still continuously occur, so surveillance and vaccine updates for H9N2 subtype avian influenza viruses are particularly important. (2) Methods: In this study, we constructed a stable Chinese hamster ovary cell line (CHO) to express the H9 hemagglutinin (HA) protein of the major prevalent H9N2 strain A/chicken/Daye/DY0602/2017 with genetic engineering technology, and then a subunit H9 avian influenza vaccine was prepared using the purified HA protein with a water-in-oil adjuvant. (3) Results: The results showed that the HI antibodies significantly increased after vaccination with the H9 subunit vaccine in specific-pathogen-free (SPF) chickens with a dose-dependent potency of the immunized HA protein, and the 50 µg or more per dose HA protein could provide complete protection against the H9N2 virus challenge. (4) Conclusions: These results indicate that the CHO expression system could be a platform used to develop the subunit vaccine against H9 influenza viruses in chickens.


Subject(s)
Influenza A Virus, H9N2 Subtype , Influenza Vaccines , Influenza in Birds , Animals , Humans , Cricetinae , Influenza A Virus, H9N2 Subtype/genetics , Chickens , Hemagglutinins , Cricetulus , CHO Cells , Antibodies, Viral , Vaccines, Subunit , Hemagglutinin Glycoproteins, Influenza Virus/genetics
16.
Adv Mater ; 36(15): e2310216, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38237136

ABSTRACT

The sprayable hydrogel coatings that can establish robust adhesion onto diverse materials and devices hold enormous potential; however, a significant challenge persists due to monomer hydration, which impedes even coverage during spraying and induces inadequate adhesion post-gelation. Herein, a polycation-reinforced (PCR) surface bridging strategy is presented to achieve tough and sprayable hydrogel coatings onto diverse materials. The polycations offer superior wettability and instant electrostatic interactions with plasma-treated substrates, facilitating an effective spraying application. This PCR-based hydrogel coatings demonstrate tough adhesion performance to inert PTFE and silicone, including remarkable shear strength (161 ± 49 kPa for PTFE), interfacial toughness (198 ± 27 J m-2 for PTFE), and notable tolerance to cyclic tension (10 000 cycles, 200% strain, silicone). Meanwhile, this method can be applied to various hydrogel formulations, offering diverse functionalities, including underwater adhesion, lubrication, and drug delivery. Furthermore, the PCR concept enables the conformal construction of durable hydrogel coatings onto sophisticated medical devices like cardiovascular stents. Given its simplicity and adaptability, this approach paves an avenue for incorporating hydrogels onto solid surfaces and potentially promotes untapped applications.


Subject(s)
Hydrogels , Polyelectrolytes , Silicones , Polytetrafluoroethylene , Polymerase Chain Reaction
17.
Front Biosci (Landmark Ed) ; 29(1): 19, 2024 01 17.
Article in English | MEDLINE | ID: mdl-38287820

ABSTRACT

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy of the skin, and its incidence is increasing annually. Once cSCC becomes metastatic, its associated mortality rate is much higher than that of cSCC in situ. However, the current treatments for progressive cSCC have several limitations. The aim of this study was to suggest a potential compound for future research that may benefit patients with cSCC. METHODS: In this study, we screened the following differentially expressed genes from the Gene Expression Omnibus database: GSE42677, GSE45164, GSE66359, and GSE98767. Using strategies such as protein-protein interaction network analysis and the CYTOSCAPE plugin MCODE, key modules were identified and then verified by Western blotting. Subsequently, related signalling pathways were constituted in the SIGNOR database. Finally, molecular docking analyses and cell viability assay were used to identify a potential candidate drug and verify its growth inhibition ability to A431 cell line. RESULTS: Fifty-one common differentially expressed genes were screened and two key modules were identified. Among them, three core genes were extracted, constituting two signalling pathways, both of which belong to the module associated with mitotic spindles and cell division. A pathway involving CDK1, the TPX2-KIF11 complex, and spindle organization was validated in a series of analyses, including analyses for overall survival, genetic alteration, and molecular structure. Molecular docking analyses identified the pyridine 2-carbaldehyde thiosemicarbazone (NSC689534), which interacts with TPX2 and KIF11, as a potential candidate for the treatment of cSCC. CONCLUSIONS: NSC689534 might be a candidate drug for cSCC targeting TPX2 and KIF11, which are hub genes in cSCC.


Subject(s)
Carcinoma, Squamous Cell , Skin Neoplasms , Thiosemicarbazones , Humans , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Skin Neoplasms/drug therapy , Skin Neoplasms/genetics , Molecular Docking Simulation , Signal Transduction/genetics , Gene Expression Regulation, Neoplastic
18.
Hepatol Int ; 18(2): 550-567, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37067674

ABSTRACT

BACKGROUND: Although the elderly constitute more than a third of hepatocellular carcinoma (HCC) patients, they have not been adequately represented in treatment and prognosis studies. Thus, there is not enough evidence to guide the treatment of such patients. The objective of this study is to identify the prognostic factors of older patients with HCC and to construct a new prognostic model for predicting their overall survival (OS). METHODS: 2,721 HCC patients aged ≥ 65 were extracted from the public database-Surveillance, Epidemiology, and End Results (SEER) and randomly divided into a training set and an internal validation set with a ratio of 7:3. 101 patients diagnosed from 2008 to 2017 in the First Affiliated Hospital of Zhejiang University School of Medicine were identified as the external validation set. Univariate cox regression analyses and multivariate cox regression analyses were adopted to identify these independent prognostic factors. A predictive nomogram-based risk stratification model was proposed and evaluated using area under the receiver operating characteristic curve (AUC), calibration curves, and a decision curve analysis (DCA). RESULTS: These attributes including age, sex, marital status, T stage, N stage, surgery, chemotherapy, tumor size, alpha-fetoprotein level, fibrosis score, bone metastasis, lung metastasis, and grade were the independent prognostic factors for older patients with HCC while predicting survival duration. We found that the nomogram provided a good assessment of OS at 1, 3, and 5 years in older patients with HCC (1-year OS: (training set: AUC = 0.823 (95%CI 0.803-0.845); internal validation set: AUC = 0.847 (95%CI 0.818-0.876); external validation set: AUC = 0.732 (95%CI 0.521-0.943)); 3-year OS: (training set: AUC = 0.813 (95%CI 0.790-0.837); internal validation set: AUC = 0.844 (95%CI 0.812-0.876); external validation set: AUC = 0.780 (95%CI 0.674-0.887)); 5-year OS: (training set: AUC = 0.839 (95%CI 0.806-0.872); internal validation set: AUC = 0.800 (95%CI 0.751-0.849); external validation set: AUC = 0.821 (95%CI 0.727-0.914)). The calibration curves showed that the nomogram was with strong calibration. The DCA indicated that the nomogram can be used as an effective tool in clinical practice. The risk stratification of all subgroups was statistically significant (p < 0.05). In the stratification analysis of surgery, larger resection (LR) achieved a better survival curve than local destruction (LD), but a worse one than segmental resection (SR) and liver transplantation (LT) (p < 0.0001). With the consideration of the friendship to clinicians, we further developed an online interface (OHCCPredictor) for such a predictive function ( https://juntaotan.shinyapps.io/dynnomapp_hcc/ ). With such an easily obtained online tool, clinicians will be provided helpful assistance in formulating personalized therapy to assess the prognosis of older patients with HCC. CONCLUSIONS: Age, sex, marital status, T stage, N stage, surgery, chemotherapy, tumor size, AFP level, fibrosis score, bone metastasis, lung metastasis, and grade were independent prognostic factors for elderly patients with HCC. The constructed nomogram model based on the above factors could accurately predict the prognosis of such patients. Besides, the developed online web interface of the predictive model provide easily obtained access for clinicians.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Lung Neoplasms , Aged , Humans , Risk Assessment , Fibrosis , Prognosis
19.
Biochem Genet ; 62(1): 452-467, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37380850

ABSTRACT

Rotator cuff tear (RCT) is a common shoulder disorder related to pain and dysfunction. However, the pathological mechanism of RCT remains unclear. Thus, this study aims to investigate the molecular events in RCT synovium and identify possible target genes and pathways as determined by RNA sequencing (RNA-Seq). The synovial tissue was biopsied from 3 patients with RCT (RCT group) and 3 patients with shoulder instability (Control group) during arthroscopic surgery. Then, differentially expressed (DE) mRNAs, long non-coding RNAs (lncRNAs) and micro RNAs (miRNAs) were comprehensively profiled by RNA-Seq. Gene ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and competing endogenous RNA (ceRNA) network analysis were performed to identify the potential functions of these DE genes. 447 mRNAs, 103 lncRNAs and 15 miRNAs were identified differentially expressed. The DE mRNAs were highlighted in inflammatory pathway including up-regulated T cell costimulation, positive regulation of T cell activation, and T cell receptor signaling. Down-regulated fatty acid degradation pathway and 5'-AMP-activated protein kinase (AMPK) signaling in RCT group are also enriched. Validation assay showed that the expression of pro-inflammatory molecules including IL21R, CCR5, TNFSF11, and MMP11 was significantly increased in RCT group compared with Control group. CeRNA analysis further revealed lncRNA-miRNA-mRNA regulatory networks involving IL21R and TNFSF11 in RCT. Activated synovial inflammation is the remarkable event of RCT. Importantly, increased T cell activation and disordered fatty acid metabolism signaling might play a significant role. ceRNA networks involving IL21R and TNFSF11 identified could potentially control the progression of RCT. In conclusion, our findings could provide new evidence for the molecular mechanisms of RCT and might identify new therapeutic targets.


Subject(s)
MicroRNAs , RNA, Long Noncoding , Rotator Cuff Injuries , Humans , Rotator Cuff Injuries/genetics , Rotator Cuff Injuries/surgery , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Gene Regulatory Networks , MicroRNAs/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Sequence Analysis, RNA , Receptors, Interleukin-21/genetics , Gene Expression , Fatty Acids
20.
Photochem Photobiol ; 100(2): 380-392, 2024.
Article in English | MEDLINE | ID: mdl-38041414

ABSTRACT

We have employed the highly accurate multistate complete active space second-order perturbation theory (MS-CASPT2) method to investigate the photoinduced excited state relaxation properties of one unnatural base, namely Z. Upon excitation to the S2 state of Z, the internal conversion to the S1 state would be dominant. From the S1 state, two intersystem crossing paths leading to the T2 and T1 states and one internal conversion path to the S0 state are possible. However, considering the large barrier to access the S1 /S0 conical intersection and the strong spin-orbit coupling between S1 and T2 states (>40 cm-1 ), the intersystem crossing to the triplet manifolds is predicted to be more preferred. Arriving at the T2 state, the internal conversion to the T1 state and the intersystem crossing back to the S1 state are both possible considering the S1 /T2 /T1 three-state intersection near the T2 minimum. Upon arrival at the T1 state, the deactivation to S0 can be efficient after overcoming a small barrier to access T1 /S0 crossing point, where the spin-orbit coupling (SOC) is as large as 39.7 cm-1 . Our present work not only provides in-depth insights into the photoinduced process of unnatural base Z, but can also help the future design of novel unnatural bases with better photostability.

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