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1.
BMC Infect Dis ; 24(1): 565, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38844855

ABSTRACT

BACKGROUND: The effectiveness of post-exposure prophylaxis (PEP) depends on participants adherence, making it crucial to assess and compare regimen options to enhance human immunodeficiency virus (HIV) prophylaxis strategies. However, no prospective study in China has shown that the completion rate and adherence of single-tablet regimens in HIV PEP are higher than those of multi-tablet preparations. Therefore, this study aimed to assess the completion rate and adherence of two HIV PEP regimens. METHODS: In this single-center, prospective, open-label cohort study, we included 179 participants from May 2022 to March 2023 and analyzed the differences in the 28-day medication completion rate, adherence, safety, tolerance, and effectiveness of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and tenofovir disoproxil fumarate, emtricitabine, and dolutegravir (TDF/FTC + DTG). RESULTS: The PEP completion rate and adherence were higher in the BIC/FTC/TAF group than in the TDF/FTC + DTG group (completion rate: 97.8% vs. 82.6%, P = 0.009; adherence: 99.6 ± 2.82% vs. 90.2 ± 25.29%, P = 0.003). The incidence of adverse reactions in the BIC/FTC/TAF and TDF/FTC + DTG groups was 15.2% and 10.3% (P = 0.33), respectively. In the TDF/FTC + DTG group, one participant stopped PEP owing to adverse reactions (1.1%). No other participants stopped PEP due to adverse events. CONCLUSIONS: BIC/FTC/TAF and TDF/FTC + DTG have good safety and tolerance as PEP regimens. BIC/FTC/TAF has a higher completion rate and increased adherence, thus, is recommended as a PEP regimen. These findings emphasize the importance of regimen choice in optimizing PEP outcomes. TRIAL REGISTRATION: The study was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2200059994(2022-05-14), https://www.chictr.org.cn/bin/project/edit?pid=167391 ).


Subject(s)
Amides , Anti-HIV Agents , Drug Combinations , Emtricitabine , HIV Infections , Heterocyclic Compounds, 3-Ring , Post-Exposure Prophylaxis , Pyridones , Tenofovir , Humans , HIV Infections/prevention & control , Prospective Studies , Male , Emtricitabine/therapeutic use , Emtricitabine/administration & dosage , Tenofovir/therapeutic use , Tenofovir/administration & dosage , Tenofovir/analogs & derivatives , China , Adult , Female , Anti-HIV Agents/therapeutic use , Anti-HIV Agents/administration & dosage , Amides/therapeutic use , Amides/administration & dosage , Heterocyclic Compounds, 3-Ring/therapeutic use , Heterocyclic Compounds, 3-Ring/administration & dosage , Middle Aged , Post-Exposure Prophylaxis/methods , Medication Adherence/statistics & numerical data , Heterocyclic Compounds, 4 or More Rings/therapeutic use , Heterocyclic Compounds, 4 or More Rings/administration & dosage , Alanine/therapeutic use , Alanine/administration & dosage , Adenine/analogs & derivatives , Adenine/therapeutic use , Adenine/administration & dosage , Young Adult , Piperazines
2.
Eur J Immunol ; : e2350603, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38752316

ABSTRACT

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by persistent activation of immune cells and overproduction of autoantibodies. The accumulation of senescent T and B cells has been observed in SLE and other immune-mediated diseases. However, the exact mechanistic pathways contributing to this process in SLE remain incompletely understood. In this study, we found that in SLE patients: (1) the frequency of CD4+CD57+ senescent T cells was significantly elevated and positively correlated with disease activity; (2) the expression levels of B-lymphoma-2 (BCL-2) family and interferon-induced genes (ISGs) were significantly upregulated; and (3) in vitro, the cytokine IL-15 stimulation increased the frequency of senescent CD4+ T cells and upregulated the expression of BCL-2 family and ISGs. Further, treatment with ABT-263 (a senolytic BCL-2 inhibitor) in MRL/lpr mice resulted in decreased: (1) frequency of CD4+CD44hiCD62L-PD-1+CD153+ senescent CD4+ T cells; (2) frequency of CD19+CD11c+T-bet+ age-related B cells; (3) level of serum antinuclear antibody; (4) proteinuria; (5) frequency of Tfh cells; and (6) renal histopathological abnormalities. Collectively, these results indicated a dominant role for CD4+CD57+ senescent CD4+ T cells in the pathogenesis of SLE and senolytic BCL-2 inhibitor ABT-263 may be the potential treatment in ameliorating lupus phenotypes.

3.
Adv Mater ; : e2404199, 2024 May 12.
Article in English | MEDLINE | ID: mdl-38734974

ABSTRACT

External stimuli triggering chemical reactions in cancer cells to generate highly reactive chemical species are very appealing for cancer therapy, in which external irradiation activating sensitizers to transfer energy or electrons to surrounding oxygen or other molecules is critical for generating cytotoxic reactive species. However, poor light penetration into tissue, low activity of sensitizers, and reliance on oxygen supply restrict the generation of cytotoxic chemical species in hypoxic tumors, which lowers the therapeutic efficacy. Here, this work presents galvanic cell nanomaterials that can directly release highly reactive electrons in tumors without external irradiation or photosensitizers. The released reactive electrons directly react with surrounding biomolecules such as proteins and DNA within tumors to destroy them or react with other surrounding (bio)molecules to yield cytotoxic chemical species to eliminate tumors independent of oxygen. Administering these nanogalvanic cells to mice results in almost complete remission of subcutaneous solid tumors and deep metastatic tumors. The results demonstrate that this strategy can further arouse an immune response even in a hypoxic environment. This method offers a promising approach to effectively eliminate tumors, similar to photodynamic therapy, but does not require oxygen or irradiation to activate photosensitizers.

5.
Article in English | MEDLINE | ID: mdl-38753724

ABSTRACT

In China, non-nucleoside reverse transcriptase inhibitors (NNRTIs) are integral to the antiretroviral therapy (ART) regimen for persons living with HIV (PWH), comprising over 80% of such treatments. To broaden treatment options and improve therapeutic effectiveness, Ainuovirine (ANV), a new NNRTI, was authorized for ART in 2021. Nevertheless, the clinical efficacy of ANV and its impact on blood biochemical markers remain somewhat underexplored. This study seeks to evaluate ANV's clinical performance in ART and its influence on relevant treatment parameters. A retrospective analysis was performed on 208 patients treated with an ANV-based regimen from July 2021 to July 2023, monitoring indicator changes from baseline to week 24. The primary endpoint was the proportion of participants achieving HIV-1 RNA levels of less than 50 copies/mL by week 24. Secondary endpoints involved assessing variations in CD4+ T cell counts and blood biochemical markers from baseline. These outcomes were also compared with data from 241 patients treated with an Efavirenz (EFV)-based regimen in the same time frame. The findings suggest that the ANV-based regimen is as effective as the EFV-based regimen in viral suppression (p > .05) and offers superior improvements in lipid profiles, liver function, and immune system indicators, alongside fewer adverse reactions. These results affirm ANV's efficacy and safety as an antiretroviral therapy option, offering Acquired Immune Deficiency Syndrome patients a wider array of treatment possibilities and the potential for better treatment outcomes.

6.
Exp Dermatol ; 33(4): e15082, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38664884

ABSTRACT

As a chronic relapsing disease, psoriasis is characterized by widespread skin lesions. The Psoriasis Area and Severity Index (PASI) is the most frequently utilized tool for evaluating the severity of psoriasis in clinical practice. Nevertheless, long-term monitoring and precise evaluation pose difficulties for dermatologists and patients, which is time-consuming, subjective and prone to evaluation bias. To develop a deep learning system with high accuracy and speed to assist PASI evaluation, we collected 2657 high-quality images from 1486 psoriasis patients, and images were segmented and annotated. Then, we utilized the YOLO-v4 algorithm to establish the model via four modules, we also conducted a human-computer comparison through quadratic weighted Kappa (QWK) coefficients and intra-class correlation coefficients (ICC). The YOLO-v4 algorithm was selected for model training and optimization compared with the YOLOv3, RetinaNet, EfficientDet and Faster_rcnn. The model evaluation results of mean average precision (mAP) for various lesion features were as follows: erythema, mAP = 0.903; scale, mAP = 0.908; and induration, mAP = 0.882. In addition, the results of human-computer comparison also showed a median consistency for the skin lesion severity and an excellent consistency for the area and PASI score. Finally, an intelligent PASI app was established for remote disease assessment and course management, with a pleasurable agreement with dermatologists. Taken together, we proposed an intelligent PASI app based on the image YOLO-v4 algorithm that can assist dermatologists in long-term and objective PASI scoring, shedding light on similar clinical assessments that can be assisted by computers in a time-saving and objective manner.


Subject(s)
Algorithms , Deep Learning , Psoriasis , Severity of Illness Index , Psoriasis/pathology , Humans , Image Processing, Computer-Assisted/methods
7.
Immun Inflamm Dis ; 12(4): e1217, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38578026

ABSTRACT

INTRODUCTION: The efficacy and safety of ainuovirine+lamivudine+tenofovir (ANV+3TC+TDF) and efavirenz+lamivudine+tenofovir (EFV+3TC+TDF) have been confirmed in previous clinical trials; however, there are no related studies on patient-reported outcomes. This study aimed to evaluate the effectiveness and safety of these 2 antiretroviral therapy regimens and to understand the patient's symptom experience and subjective experience of sleep quality through patient-reported outcomes. METHODS: This is a single-center prospective cohort study with 243 patients evaluated from October 1, 2021 to June 30, 2022. Virological effectiveness and patient-reported outcomes results were analyzed. The primary endpoint was the proportion of HIV viral load <50 copies/mL (virological suppression rate) at 48 weeks and the changes in the HIV symptom index and Pittsburgh sleep quality index. RESULTS: The virological suppression rates in the ANV+3TC+TDF and EFV+3TC+TDF groups were 83.6% (102/122) and 87.6% (106/121), respectively, at 48 weeks. In the ANV+3TC+TDF group, the scores of HIV symptom index and pittsburgh sleep quality index in the 48th week were lower than the baseline level (p < 0.05). Logistic regression results showed that the baseline regimen EFV+3TC+TDF was a risk factor for dizziness/lightheadedness (odds ratio = 3.153, 95% confidence interval: 1.473-6.748, p = 0.003), sadness/depression odds ratio = 2.404, 95% confidence interval:1.188-4.871, p = 0.015), and difficulty sleeping (odds ratio = 2.802, 95% confidence interval: 1.437-5.463, p = 0.002) at 48 weeks. CONCLUSIONS: Both regimens showed good virological effectiveness; however, compared with ANV+3TC+TDF, the EFV+3TC+TDF regimen reduced the prevalence of HIV-related symptoms.


Subject(s)
Anti-HIV Agents , HIV Infections , Humans , Reverse Transcriptase Inhibitors/adverse effects , Lamivudine/therapeutic use , Anti-HIV Agents/adverse effects , Prospective Studies , HIV Infections/drug therapy , HIV Infections/epidemiology , Tenofovir/therapeutic use
8.
J Environ Manage ; 358: 120909, 2024 May.
Article in English | MEDLINE | ID: mdl-38642487

ABSTRACT

Achieving an equilibrium between exceptional oil absorption and remarkable elasticity has emerged as a formidable challenge for magnetic porous materials designed for oil absorption. Here, we propose an original, magnetic and superhydrophobic cellulose nanofibril (CNF) based aerogel system with a rope-ladder like skeleton by to greatly improve the issue. Within this system, CNF as the skeleton was combined with multiwalled carbon nanotubes (MWCNT)@Fe3O4 as the magnetic and enhanced component, both methyltrimethoxysilane (MTMS) and acetonitrile-extracted lignin (AEL) as the soft-hard associating constituents. The resultant CNF based aerogel shows a rope-ladder like pore structure to contribute to high elasticity and excellent oil absorption (28.34-61.09 g/g for various oils and organic solvents) under the synergistic effect of Fe3O4@MWCNT, AEL and MTMS, as well as good specific surface area (27.97 m2/g), low density (26.4 mg/cm3). Notably, despite the introduced considerable proportion (0.5 times of mass-CNF) of Fe3O4@MWCNT, the aerogel retained an impressive compression-decompression rate (88%) and the oil absorption efficiency of above 87% for various oils due to the soft-hard associating structure supported by both MTMS and AEL. This study provides a prospective strategy to balance between high elasticity and excellent oil absorption of CNF based aerogel doping inorganic particles.


Subject(s)
Cellulose , Hydrophobic and Hydrophilic Interactions , Nanofibers , Cellulose/chemistry , Nanofibers/chemistry , Oils/chemistry , Gels/chemistry , Nanotubes, Carbon/chemistry , Elasticity , Porosity
9.
J Pers Med ; 14(4)2024 Mar 30.
Article in English | MEDLINE | ID: mdl-38673000

ABSTRACT

Scabies is a neglected tropical disease and represents a considerable global burden. Although consensus diagnostic criteria for scabies have been recently published, diagnosing scabies infestation remains challenging in clinical practice. We investigated the diagnostic utility of complete blood cell count (CBC) and CBC-derived ratios obtained at diagnosis in a set of 167 patients who are Vietnamese with confirmed scabies. These parameters were compared with those of patients with dermatophytosis (N = 800) and urticaria (N = 2023), two diseases frequent in Vietnam, which can present with similar skin manifestations to scabies and tend to pose a diagnostic challenge in vulnerable populations. Our analysis revealed that white blood cell, monocyte, and eosinophil counts were significantly higher among patients with scabies than the other two diseases. Similarly, the monocyte-to-lymphocyte ratio (MLR) and eosinophil-to-lymphocyte ratio (ELR) were significantly higher among patients with scabies. The optimal cut-off values to distinguish scabies from dermatophytosis and urticaria were 0.094 for ELR (sensitivity: 74.85%, specificity: 70.7%) and 0.295 for MLR (sensitivity: 52.69%, specificity: 73.54%). CBC, ELR, and MLR are low-cost and easily calculated parameters that may be helpful for the diagnosis of scabies.

10.
J Autoimmun ; 146: 103203, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38643729

ABSTRACT

Lupus erythematosus (LE) is a heterogeneous, antibody-mediated autoimmune disease. Isolate discoid LE (IDLE) and systematic LE (SLE) are traditionally regarded as the two ends of the spectrum, ranging from skin-limited damage to life-threatening multi-organ involvement. Both belong to LE, but IDLE and SLE differ in appearance of skin lesions, autoantibody panels, pathological changes, treatments, and immunopathogenesis. Is discoid lupus truly a form of LE or is it a completely separate entity? This question has not been fully elucidated. We compared the clinical data of IDLE and SLE from our center, applied multi-omics technology, such as immune repertoire sequencing, high-resolution HLA alleles sequencing and multi-spectrum pathological system to explore cellular and molecular phenotypes in skin and peripheral blood from LE patients. Based on the data from 136 LE patients from 8 hospitals in China, we observed higher damage scores and fewer LE specific autoantibodies in IDLE than SLE patients, more uCDR3 sharing between PBMCs and skin lesion from SLE than IDLE patients, elevated diversity of V-J recombination in IDLE skin lesion and SLE PBMCs, increased SHM frequency and class switch ratio in IDLE skin lesion, decreased SHM frequency but increased class switch ratio in SLE PBMCs, HLA-DRB1*03:01:01:01, HLA-B*58:01:01:01, HLA-C*03:02:02:01, and HLA-DQB1*02:01:01:01 positively associated with SLE patients, and expanded Tfh-like cells with ectopic germinal center structures in IDLE skin lesions. These findings suggest a significant difference in the immunopathogenesis of skin lesions between SLE and IDLE patients. SLE is a B cell-predominate systemic immune disorder, while IDLE appears limited to the skin. Our findings provide novel insights into the pathogenesis of IDLE and other types of LE, which may direct more accurate diagnosis and novel therapeutic strategies.


Subject(s)
Autoantibodies , Lupus Erythematosus, Discoid , Lupus Erythematosus, Systemic , Skin , Humans , Lupus Erythematosus, Discoid/immunology , Lupus Erythematosus, Discoid/pathology , Female , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/diagnosis , Male , Autoantibodies/immunology , Autoantibodies/blood , Skin/pathology , Skin/immunology , Skin/metabolism , Adult , Middle Aged , Alleles , HLA Antigens/genetics , HLA Antigens/immunology , Young Adult , Multiomics
11.
Biosci Trends ; 18(2): 176-186, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38684402

ABSTRACT

This study aimed to compare the efficacy and effect on lipid profiles of Ainuovirine (ANV)- and efavirenz (EFV) -based regimens in treatment-naïve people living with HIV-1 (PLWH) at week 24. The proportion of PLWH achieving HIV-1 RNA < the limit of quantification in the ANV group was significantly higher than that in the EFV group (89.18% vs. 76.04%, P = 0.002). The mean change of log10 HIV-1 RNA from baseline was greater (-4.34 vs. -4.18, P < 0.001), the median change from baseline in CD4+ T cell count increased more (106.00 cells/µL vs. 92.00 cells/µL, P = 0.007) in the ANV group, while the CD4+/CD8+ ratio was similar (0.15 vs. 0.20, P = 0.167) between the two groups. The mean changes from baseline in total cholesterol (-0.02 for ANV vs. 0.25 mmol/L for EFV, P < 0.001), triglyceride (-0.14 for ANV vs. 0.11 mmol/L for EFV, P = 0.024), and low-density lipoprotein cholesterol (-0.07 for ANV vs. 0.15 mmol/L for EFV, P < 0.001) was significantly different between the two groups. The percentage of patients with improved lipid profiles was significantly higher in the ANV group (37.44 %) than in the EFV group (29.55%, P = 0.0495). The incidence of any adverse events in the ANV group was significantly lower than that in the EFV group at week 12 (6.2% vs. 30.7%, P < 0.001) and was comparable at week 24 (3.6% vs. 5.5%, P = 0.28). The ANV-based regimen was well tolerated and lipid-friendly in treatment-naïve PLWH.


Subject(s)
Alkynes , Anti-HIV Agents , Benzoxazines , Cyclopropanes , HIV Infections , HIV-1 , Humans , Cyclopropanes/therapeutic use , Cyclopropanes/administration & dosage , Benzoxazines/therapeutic use , Alkynes/therapeutic use , HIV Infections/drug therapy , HIV Infections/blood , HIV Infections/virology , HIV-1/drug effects , Male , Female , Adult , Retrospective Studies , Anti-HIV Agents/therapeutic use , Lipids/blood , Middle Aged , Treatment Outcome , CD4 Lymphocyte Count
12.
Article in English | MEDLINE | ID: mdl-38619440

ABSTRACT

BACKGROUND: Lupus erythematosus (LE) is a spectrum of autoimmune diseases. Due to the complexity of cutaneous LE (CLE), clinical skin image-based artificial intelligence is still experiencing difficulties in distinguishing subtypes of LE. OBJECTIVES: We aim to develop a multimodal deep learning system (MMDLS) for human-AI collaboration in diagnosis of LE subtypes. METHODS: This is a multi-centre study based on 25 institutions across China to assist in diagnosis of LE subtypes, other eight similar skin diseases and healthy subjects. In total, 446 cases with 800 clinical skin images, 3786 multicolor-immunohistochemistry (multi-IHC) images and clinical data were collected, and EfficientNet-B3 and ResNet-18 were utilized in this study. RESULTS: In the multi-classification task, the overall performance of MMDLS on 13 skin conditions is much higher than single or dual modals (Sen = 0.8288, Spe = 0.9852, Pre = 0.8518, AUC = 0.9844). Further, the MMDLS-based diagnostic-support help improves the accuracy of dermatologists from 66.88% ± 6.94% to 81.25% ± 4.23% (p = 0.0004). CONCLUSIONS: These results highlight the benefit of human-MMDLS collaborated framework in telemedicine by assisting dermatologists and rheumatologists in the differential diagnosis of LE subtypes and similar skin diseases.

13.
Ann Indian Acad Neurol ; 27(1): 27-33, 2024.
Article in English | MEDLINE | ID: mdl-38495252

ABSTRACT

Background: Potentially substantial impacts on the prognosis have been observed in individuals undergoing endovascular treatment due to cytochrome P450 2c19 (CYP2C19) polymorphism. In an attempt to improve prognosis and lower the recurrence rate, this study investigated the CYP2C19 polymorphism in acute ischemic stroke patients. Materials and Methods: A retrospective analysis was performed on 292 patients with cerebral infarction who had acute endovascular recanalization at the Department of Neurology of Chongqing Hospital of Traditional Chinese Medicine between May 2017 and 2019. The patients were categorized into rapid-, medium-, and slow-metabolism groups based on CYP2C19 gene polymorphism, and their prognosis was monitored. In addition, the prognosis of 188 patients selectively receiving carotid artery stenting at a selected time was also observed. Results: Among the 292 cerebral infarction cases receiving acute endovascular recanalization, the patients in the CYP2C19 rapid-metabolism group regularly took clopidogrel and aspirin combined with antiplatelet therapy and suffered from reoccurrence of apoplexy and cerebral hemorrhage; the 90-day good prognosis had a statistical difference (P < 0.05, prognostic assessment includes hospitalization and 6 months after discharge) and the other adverse events had no statistical difference (including mortality). The 188 patients selectively receiving carotid artery stenting had a recurrence of apoplexy, cerebral hemorrhage, and restenosis rate with a statistical difference (P < 0.05), and the other adverse events had no statistical difference. Conclusions: In conclusion, the findings of the current study indicate that irrespective of whether patients are undergoing selective carotid artery stenting or acute endovascular recanalization, those with rapid CYP2C19 metabolism have a significantly lower likelihood of experiencing adverse prognostic events compared to those with intermediate and slow metabolism. Furthermore, this group also has a more favorable prognosis than the other two groups.

14.
Spectrochim Acta A Mol Biomol Spectrosc ; 314: 124187, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38547781

ABSTRACT

A bis(salamo)-like chemical sensor H3L ((1E,3E)-2-hydroxy-5-methylisophthalaldehyde O,O -di(3-((((E)-(2-hydroxynaphthalen-1-yl)methylene)amino)oxy)propyl) dioxime) was constructed. H3L is capable of recognizing B4O72- in H2O/DMF (1:9, v/v) solution by both fluorescent and colorimetric channels, bright green fluorescence was turned on when B4O72- was added to H3L and changed from colorless to yellow in natural light. The detection limit was 3.21 × 10-8 M. The identification has good anti-interfering ability, quickly responsive time (5 S) and broad pH detecting range (pH = 5-12). The mechanism of action was determined by 1H NMR titration, infrared spectrometry, HRMS spectra and further elucidated by theory calculations. The fluorescence imaging of bean sprouts and spiked recovery assays of actual water samples demonstrated the practical use of sensor H3L for the detection of B4O72-, which is expected to have applications for the detection of B4O72- in plants and the environment.

15.
World J Gastrointest Oncol ; 16(2): 259-272, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38425391

ABSTRACT

Approximately 20% of colorectal cancer (CRC) patients present with metastasis at diagnosis. Among Stage I-III CRC patients who undergo surgical resection, 18% typically suffer from distal metastasis within the first three years following initial treatment. The median survival duration after the diagnosis of metastatic CRC (mCRC) is only 9 mo. mCRC is traditionally considered to be an advanced stage malignancy or is thought to be caused by incomplete resection of tumor tissue, allowing cancer cells to spread from primary to distant organs; however, increasing evidence suggests that the mCRC process can begin early in tumor development. CRC patients present with high heterogeneity and diverse cancer phenotypes that are classified on the basis of molecular and morphological alterations. Different genomic and nongenomic events can induce subclone diversity, which leads to cancer and metastasis. Throughout the course of mCRC, metastatic cascades are associated with invasive cancer cell migration through the circulatory system, extravasation, distal seeding, dormancy, and reactivation, with each step requiring specific molecular functions. However, cancer cells presenting neoantigens can be recognized and eliminated by the immune system. In this review, we explain the biological factors that drive CRC metastasis, namely, genomic instability, epigenetic instability, the metastatic cascade, the cancer-immunity cycle, and external lifestyle factors. Despite remarkable progress in CRC research, the role of molecular classification in therapeutic intervention remains unclear. This review shows the driving factors of mCRC which may help in identifying potential candidate biomarkers that can improve the diagnosis and early detection of mCRC cases.

16.
BMC Plant Biol ; 24(1): 159, 2024 Mar 02.
Article in English | MEDLINE | ID: mdl-38429715

ABSTRACT

BACKGROUND: Flower buds of Anthurium andraeanum frequently cease to grow and abort during the early flowering stage, resulting in prolonged planting times and increased commercialization costs. Nevertheless, limited knowledge exists of the mechanism of flower development after initiation in A. andraeanum. RESULTS: In this study, the measurement of carbohydrate flow and intensity between leaves and flowers during different growth stages showed that tender leaves are strong sinks and their concomitant flowers are weak ones. This suggested that the tender leaves compete with their concomitant flower buds for carbohydrates during the early growth stages, potentially causing the abortion of the flower buds. The analysis of transcriptomic differentially expressed genes suggested that genes related to sucrose metabolism and auxin response play an important role during flower bud development. Particularly, co-expression network analysis found that AaSPL12 is a hub gene engaged in flower development by collaborating carbohydrate and auxin signals. Yeast Two Hybrid assays revealed that AaSPL12 can interact with AaARP, a protein that serves as an indicator of dormancy. Additionally, the application of exogenous IAA and sucrose can suppress the expression of AaARP, augment the transcriptional abundance of AaSPL12, and consequently expedite flower development in Anthurium andraeanum. CONCLUSIONS: Collectively, our findings indicated that the combination of auxin and sugar signals could potentially suppress the repression of AaARP protein to AaSPL12, thus advancing the development of flower buds in Anthurium andraeanum.


Subject(s)
Araceae , Reproduction , Female , Pregnancy , Humans , Sucrose , Araceae/genetics , Flowers/genetics , Indoleacetic Acids
17.
Pest Manag Sci ; 80(6): 2710-2723, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38358029

ABSTRACT

BACKGROUND: Xanthomonas oryzae pv. oryzae (Xoo) is often considered one of the most destructive bacterial pathogens causing bacterial leaf blight (BLB), resulting in significant yield and cost losses in rice. In this study, a series of novel derivatives containing the isopropanolamine moiety linked to various substituted phenols and piperazines were designed, synthesized and screened. RESULTS: Antibacterial activity results showed that most compounds had good inhibitory effects on Xoo, among which compound W2 (EC50 = 2.74 µg mL-1) exhibited the most excellent inhibitory activity, and W2 also had a certain curative effect (35.89%) on rice compared to thiodiazole copper (TC) (21.57%). Scanning electron microscopy (SEM) results indicated that compound W2 could cause rupture of the Xoo cell membrane. Subsequently, proteomics and quantitative real-time polymerase chain reaction revealed that compound W2 affected the physiological processes of Xoo and may exert antibacterial activity by targeting the two-component system pathway. Interestingly, W2 upregulated Xoo's methyltransferase to impact on its pathogenicity. CONCLUSION: The present study offers a promising phenolic-piperazine-sopropanolamine compound as an innovative antibacterial strategy by specifically targeting the two-component system pathway and inducing upregulation of methyltransferase to effectively impact Xoo's pathogenicity. © 2024 Society of Chemical Industry.


Subject(s)
Anti-Bacterial Agents , Xanthomonas , Xanthomonas/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Phenols/pharmacology , Phenols/chemistry , Drug Design , Piperazines/pharmacology , Piperazines/chemistry , Piperazines/chemical synthesis , Oryza/microbiology , Plant Diseases/microbiology
18.
Clin Cosmet Investig Dermatol ; 17: 103-110, 2024.
Article in English | MEDLINE | ID: mdl-38234694

ABSTRACT

Necrotizing fasciitis is a rare, severe, rapidly progressing disease with a high mortality rate. We report a case of a 72-year female with erythematous pemphigus who developed erythema, swelling and ulceration on right vulva, groin, and thigh. The early clinical manifestations of the patient were nonspecific and easily misdiagnosed as cellulitis. However, upon the occurrence of ulceration and necrosis, deep fungal infection, pyoderma gangrenosum or lymphoproliferative disorders were considered. The pathology suggested IgG4-related diseases, plasmacytoma et al. But at last, surgical exploration and postoperative pathology confirmed the diagnosis of necrotizing fasciitis. The patient recovered after multiple aggressive surgical debridement procedures and antibiotic therapy and the patient has been followed up for 2 years without recurrence. Clinicians should be vigilant about the possibility of necrotizing fasciitis in patients with erythema, pain, rapid ulceration of skin and soft tissue, particularly in immunocompromised individuals with long-term use of immunosuppressive agents. It is crucial for saving life by early multi-disciplinary consultation, prompt diagnosis, and aggressive treatment.

19.
Expert Rev Anti Infect Ther ; 22(4): 211-217, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38058002

ABSTRACT

BACKGROUND: This study aimed to evaluate the therapeutic effect and tolerance of bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF) use for 24 weeks in anti-retroviral therapy (ART)-naïve patients in China. METHODS: This single-center retrospective cohort study included ART-naïve patients who received BIC/FTC/TAF from July 2021 to April 2022. The proportion of patients with HIV RNA < 50 copies/mL at the end point of 24 weeks (virological suppression rate) was the primary outcome, and the changes in CD4 cell count, CD4/CD8 ratio, weight, blood lipid, and safety were secondary outcomes. RESULTS: A total of 80 ART-naïve patients were enrolled. The virological suppression rate was 86.3% at 24 weeks. The median CD4 cell count increased from 212 cells/µL (interquartile range [IQR]: 90.3-398.3) at baseline to 348 cells/µL (IQR: 219.8-541.0) at 24 weeks. The median CD4/CD8 ratio increased from 0.25 (IQR: 0.13-0.37) at baseline to 0.40 (IQR: 0.26-0.66) at 24 weeks. During the follow-up of 80 ART-naïve patients using BIC/FTC/TAF, 16 participants had adverse events; however, these events did not lead to drug withdrawal. CONCLUSION: This real-world cohort study showed that BIC/FTC/TAF could achieve good immunological and virological responses in ART-naïve patients. In addition, this study also shows good safety.


Subject(s)
Adenine/analogs & derivatives , Alanine , Amides , Anti-HIV Agents , HIV Infections , HIV-1 , Piperazines , Pyridones , Tenofovir/analogs & derivatives , Adult , Humans , Retrospective Studies , Cohort Studies , Emtricitabine/adverse effects , Heterocyclic Compounds, 3-Ring/adverse effects , HIV Infections/drug therapy , Drug Combinations , Anti-HIV Agents/therapeutic use
20.
Journal of Clinical Hepatology ; (12): 611-615, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1013146

ABSTRACT

Liver fibrosis is the healing reaction of chronic liver injury caused by various factors such as viral infection, alcohol, and chemical substances and is a key link in the progression of chronic liver diseases to liver cirrhosis and liver cancer. Liver macrophages are considered important mediators of liver injury and repair, and the polarization trend of macrophages has a bidirectional regulatory effect on liver fibrosis. This article reviews the role of different phenotypes of liver macrophages in the development and progression of liver fibrosis, in order to provide new ideas for the prevention and treatment of fibrosis.

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