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1.
Water Res ; 259: 121848, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38824797

ABSTRACT

Chronic exposure to elevated geogenic arsenic (As) and fluoride (F-) concentrations in groundwater poses a significant global health risk. In regions around the world where regular groundwater quality assessments are limited, the presence of harmful levels of As and F- in shallow groundwater extracted from specific wells remains uncertain. This study utilized an enhanced stacking ensemble learning model to predict the distributions of As and F- in shallow groundwater based on 4,393 available datasets of observed concentrations and forty relevant environmental factors. The enhanced model was obtained by fusing well-suited Extreme Gradient Boosting, Random Forest, and Support Vector Machine as the base learners and a structurally simple Linear Discriminant Analysis as the meta-learner. The model precisely captured the patchy distributions of groundwater As and F- with an AUC value of 0.836 and 0.853, respectively. The findings revealed that 9.0% of the study area was characterized by a high As risk in shallow groundwater, while 21.2% was at high F- risk identified as having a high risk of fluoride contamination. About 0.2% of the study area shows elevated levels of both of them. The affected populations are estimated at approximately 7.61 million, 34.1 million, and 0.2 million, respectively. Furthermore, sedimentary environment exerted the greatest influence on distribution of groundwater As, with human activities and climate following closely behind at 29.5%, 28.1%, and 21.9%, respectively. Likewise, sedimentary environment was the primary factor affecting groundwater F- distribution, followed by hydrogeology and soil physicochemical properties, contributing 27.8%, 24.0%, and 23.3%, respectively. This study contributed to the identification of health risks associated with shallow groundwater As and F-, and provided insights into evaluating health risks in regions with limited samples.

2.
Sex Med ; 12(3): qfae027, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38827362

ABSTRACT

Background: There are no clear conclusions as to whether inflammatory proteins and plasma metabolites influence erectile dysfunction (ED). Aim: In this research, we used Mendelian randomization (MR) analysis to discover a causal relationship between inflammatory proteins, plasma metabolites, and ED. Methods: Raw data with ED, inflammatory proteins, and plasma metabolites were obtained from the MRC IEU OpenGWAS and FinnGen database. After a series of screenings, the remaining single nucleotide polymorphisms were selected as instrumental variables or MR analysis to assess the relationship between genetically predicted inflammatory proteins or plasma metabolites and the pathogenesis of ED. Outcomes: The relationship between inflammatory factors and ED was fully analyzed and elaborated. Results: In the inverse variance-weighted method, there exists a significant causal relationship between 4 types of genetically predicted inflammatory proteins and 50 types of plasma metabolites with the incidence of ED. The primary discovery is that 3 inflammatory proteins, fibroblast growth factor 5, interleukin-22 receptor subunit alpha-1, and protein S100-A12, can impact the risk of ED through plasma metabolites. Clinical Implications: ED metabolites and inflammatory proteins are also closely associated with cardiovascular diseases, warranting further exploration. Strengths and Limitations: Our analysis is based on a European population, limiting its generalizability, the genome-wide association study dataset for ED has a relatively small number of cases, and we hope for larger genome-wide association study datasets for future validation. Conclusion: This study has identified that inflammatory proteins can influence ED through plasma metabolites.

3.
Front Cardiovasc Med ; 11: 1388648, 2024.
Article in English | MEDLINE | ID: mdl-38832319

ABSTRACT

Backgroud: Acute myocardial infarction (AMI) has a high morbidity rate, high mortality rate, high readmission rate, high health care costs, and a high symptomatic, psychological, and economic burden on patients. Patients with AMI usually present with multiple symptoms simultaneously, which are manifested as symptom clusters. Symptom clusters have a profound impact on the quality of survival and clinical outcomes of AMI patients. Objective: The purpose of this study was to analyze unplanned hospital readmissions among cluster groups within a 1-year follow-up period, as well as to identify clusters of acute symptoms and the characteristics associated with them that appeared in patients with AMI. Methods: Between October 2021 and October 2022, 261 AMI patients in China were individually questioned for symptoms using a structured questionnaire. Mplus 8.3 software was used to conduct latent class analysis in order to find symptom clusters. Univariate analysis is used to examine characteristics associated with each cluster, and multinomial logistic regression is used to analyze a cluster membership as an independent predictor of hospital readmission after 1-year. Results: Three unique clusters were found among the 11 acute symptoms: the typical chest symptom cluster (64.4%), the multiple symptom cluster (29.5%), and the atypical symptom cluster (6.1%). The cluster of atypical symptoms was more likely to have anemia and the worse values of Killip class compared with other clusters. The results of multiple logistic regression indicated that, in comparison to the typical chest cluster, the atypical symptom cluster substantially predicted a greater probability of 1-year hospital readmission (odd ratio 8.303, 95% confidence interval 2.550-27.031, P < 0.001). Conclusion: Out of the 11 acute symptoms, we have found three clusters: the typical chest symptom, multiple symptom, and atypical symptom clusters. Compared to patients in the other two clusters, those in the atypical symptom cluster-which included anemia and a large percentage of Killip class patients-had worse clinical indicators at hospital readmission during the duration of the 1-year follow-up. Both anemia and high Killip classification suggest that the patient's clinical presentation is poor and therefore the prognosis is worse. Intensive treatment should be considered for anemia and high level of Killip class patients with atypical presentation. Clinicians should focus on patients with atypical symptom clusters, enhance early recognition of symptoms, and develop targeted symptom management strategies to alleviate their discomfort in order to improve symptomatic outcomes.

4.
Cancer ; 2024 May 04.
Article in English | MEDLINE | ID: mdl-38703012

ABSTRACT

BACKGROUND: Previous studies involving risk-benefit analysis of trastuzumab deruxtecan (DS-8201) have indicated the benefit of this treatment, although it may increase the risk of interstitial lung disease (ILD) and/or pneumonitis in certain patients. This study aimed to assess the safety of DS-8201. METHODS: A search was done for relevant articles in four electronic databases: PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov. All reports published up until November 2, 2022, were included, and study types were restricted to clinical trials; the last search was then updated to January 10, 2023. We also assessed the quality of the literature with the Cochrane Handbook for Systematic Reviews of Interventions and the Methodological Index for Non-Randomized Studies tool, and then performed a meta-analysis with R version 4.2.1. RESULTS: A total of 1428 patients reported in 13 articles were included in this study. The analysis revealed that the most common all-grade treatment-emergent adverse events (TEAEs) were nausea and fatigue. The most common TEAE of grade 3 or above (grade ≥3) was neutropenia. The incidences of ILD and/or pneumonitis for all-grade and grade ≥3 TEAEs were 12.5% and 2.2%, respectively. CONCLUSIONS: This comprehensive summary of the incidence of TEAEs associated with DS-8201 in clinical trials provides an important guide for clinicians. The most common TEAEs were gastrointestinal reactions and fatigue; meanwhile, the most common grade ≥3 TEAE was hematological toxicity. ILD and/or pneumonitis were specific adverse drug reactions associated with DS-8201, of which physicians should be particularly aware for their higher morbidity and rates of grade ≥3 TEAEs.

5.
Food Sci Nutr ; 12(5): 3674-3687, 2024 May.
Article in English | MEDLINE | ID: mdl-38726448

ABSTRACT

American ginseng (Panax quinquefolius L.) contains various biological macromolecules, such as polysaccharides, saponins, and proteins, which have various pharmacological activities, including antioxidant, anti-inflammatory, and hypoglycemic effects. Consequently, the utilization of novel processing technologies developed an American ginseng beverage to meet people's health needs and the preferences of young people. This study was the first to use American ginseng as a primary raw material, utilizing a three-step enzymatic hydrolysis approach with cellulase, pectinase, amylase, maltase, and flavor protease enzymes to prepare an American ginseng beverage. The basic nutritional and active ingredient contents of the product were determined. The antioxidant activity of enzymatic beverages was evaluated by calculating the free radical clearance rates of DPPH and ABTS, and the effect of enzymatic beverages on α-glucosidase activity was also tested. The anti-inflammatory activity of RAW264.7 cells induced by LPS was evaluated by measuring the production of NO, TNF-α, and IL-6 during the enzymatic hydrolysis process. The results indicated that the nutritional components of American ginseng beverage products met the beverage industry standards. Moreover, the application of enzymatic hydrolysis technology had improved the antioxidant and anti-inflammatory activities of American ginseng beverages. In addition, the enzymatic beverage of American ginseng exhibited certain hypoglycemic activity. Consequently, the established enzymatic hydrolysis technology provided a reference for the production of other beverage products.

6.
Vet Med Sci ; 10(3): e1465, 2024 May.
Article in English | MEDLINE | ID: mdl-38709141

ABSTRACT

A 6-year-old male golden retriever presented with swelling of the left upper eyelid of 2 months duration, which did not improve following a course of antibiotics. Routine serum biochemistry, complete blood count and diagnostic imaging identified no clinically significant abnormalities. The mass was surgically excised, and histopathologic examination was performed. Eosinophilic granulocytic sarcoma (GS) was diagnosed based on the results of histopathology and immunohistochemistry. This is the first report of GS affecting the eyelid of a dog.


Subject(s)
Dog Diseases , Sarcoma, Myeloid , Animals , Dogs , Male , Dog Diseases/surgery , Dog Diseases/diagnosis , Dog Diseases/pathology , Sarcoma, Myeloid/veterinary , Sarcoma, Myeloid/diagnosis , Sarcoma, Myeloid/pathology , Sarcoma, Myeloid/surgery , Eyelid Neoplasms/veterinary , Eyelid Neoplasms/surgery , Eyelid Neoplasms/diagnosis , Eyelid Neoplasms/pathology
7.
J Org Chem ; 2024 May 20.
Article in English | MEDLINE | ID: mdl-38768046

ABSTRACT

Herein, we report the Pd(II)-catalyzed direct C-H arylation of pyrrolo[2,3-d]pyrimidine derivatives with aryl iodides, which is enabled by bidentate pyridine-pyridine ligands. A range of aryl iodides proved to be suitable coupling partners affording the desired products in good yields with high levels of C6 selectivity. This protocol features good tolerance of reactive functional groups, mild reaction conditions, and a simple reaction system, which provides an expeditious route to an essential class of 6-arylpyrrolo[2,3-d]pyrimidines frequently found in bioactive compounds, and provides a step-economical access to the second-generation EGFR inhibitor AEE-788.

8.
Nat Struct Mol Biol ; 2024 May 20.
Article in English | MEDLINE | ID: mdl-38769389

ABSTRACT

NADH/NAD+ redox balance is pivotal for cellular metabolism. Systematic identification of NAD(H) redox regulators, although currently lacking, would help uncover unknown effectors critically implicated in the coordination of growth metabolism. In this study, we performed a genome-scale RNA interference (RNAi) screen to globally survey the genes involved in redox modulation and identified the HES family bHLH transcription factor HES4 as a negative regulator of NADH/NAD+ ratio. Functionally, HES4 is shown to be crucial for maintaining mitochondrial electron transport chain (ETC) activity and pyrimidine synthesis. More specifically, HES4 directly represses transcription of SLC44A2 and SDS, thereby inhibiting mitochondrial choline oxidation and cytosolic serine deamination, respectively, which, in turn, ensures coenzyme Q reduction capacity for DHODH-mediated UMP synthesis and serine-derived dTMP production. Accordingly, inhibition of choline oxidation preserves mitochondrial serine catabolism and ETC-coupled redox balance. Furthermore, HES4 protein stability is enhanced under EGFR activation, and increased HES4 levels facilitate EGFR-driven tumor growth and predict poor prognosis of lung adenocarcinoma. These findings illustrate an unidentified mechanism, underlying pyrimidine biosynthesis in the intersection between serine and choline catabolism, and underscore the physiological importance of HES4 in tumor metabolism.

9.
Article in English | MEDLINE | ID: mdl-38722724

ABSTRACT

The olfactory system enables humans to smell different odors, which are closely related to emotions. The high temporal resolution and non-invasiveness of Electroencephalogram (EEG) make it suitable to objectively study human preferences for odors. Effectively learning the temporal dynamics and spatial information from EEG is crucial for detecting odor-induced emotional valence. In this paper, we propose a deep learning architecture called Temporal Attention with Spatial Autoencoder Network (TASA) for predicting odor-induced emotions using EEG. TASA consists of a filter-bank layer, a spatial encoder, a time segmentation layer, a Long Short-Term Memory (LSTM) module, a multi-head self-attention (MSA) layer, and a fully connected layer. We improve upon the previous work by utilizing a two-phase learning framework, using the autoencoder module to learn the spatial information among electrodes by reconstructing the given input with a latent representation in the spatial dimension, which aims to minimize information loss compared to spatial filtering with CNN. The second improvement is inspired by the continuous nature of the olfactory process; we propose to use LSTM-MSA in TASA to capture its temporal dynamics by learning the intercorrelation among the time segments of the EEG. TASA is evaluated on an existing olfactory EEG dataset and compared with several existing deep learning architectures to demonstrate its effectiveness in predicting olfactory-triggered emotional responses. Interpretability analyses with DeepLIFT also suggest that TASA learns spatial-spectral features that are relevant to olfactory-induced emotion recognition.


Subject(s)
Algorithms , Attention , Deep Learning , Electroencephalography , Emotions , Neural Networks, Computer , Odorants , Humans , Electroencephalography/methods , Emotions/physiology , Attention/physiology , Male , Adult , Female , Smell/physiology , Memory, Short-Term/physiology , Young Adult
10.
Sci Rep ; 14(1): 10679, 2024 05 09.
Article in English | MEDLINE | ID: mdl-38724534

ABSTRACT

The supercritical antisolvent (SAS) process was a green alternative to improve the low bioavailability of insoluble drugs. However, it is difficult for SAS process to industrialize with limited production capacity. A coaxial annular nozzle was used to prepare the microcapsules of aprepitant (APR) and polyvinylpyrrolidone (PVP) by SAS with N, N-Dimethylformamide (DMF) as solvent. Meanwhile, the effects of polymer/drug ratio, operating pressure, operating temperature and overall concentration on particles morphology, mean particle diameter and size distribution were analyzed. Microcapsules with mean diameters ranging from 2.04 µm and 9.84 µm were successfully produced. The morphology, particle size, thermal behavior, crystallinity, drug content, drug dissolution and residual amount of DMF of samples were analyzed. The results revealed that the APR drug dissolution of the microcapsules by SAS process was faster than the unprocessed APR. Furthermore, the drug powder collected every hour is in the kilogram level, verifying the possibility to scale up the production of pharmaceuticals employing the SAS process from an industrial point of view.


Subject(s)
Aprepitant , Capsules , Particle Size , Povidone , Solvents , Capsules/chemistry , Povidone/chemistry , Solvents/chemistry , Aprepitant/chemistry , Solubility , Dimethylformamide/chemistry , Drug Liberation , Drug Compounding/methods , Temperature
11.
Adv Healthc Mater ; : e2400673, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38809199

ABSTRACT

Bone metastases occur in more than 70% of advanced prostate cancer (PCa) patients, leading to a poor prognosis. Resistance to detachment-induced apoptosis, also known as anoikis, plays a crucial role in the onset of tumor metastasis. Targeting anoikis resistance is of immense therapeutic significance in repression of metastatic spread. In this study, based on an anoikis-related prognostic risk model of PCa, we identify TUBB3 as a key anoikis-related prognostic gene that is highly expressed in bone metastatic PCa. TUBB3 expression is increased in anoikis-resistant PCa cells, and TUBB3 depletion significantly reverses anoikis resistance during extracellular matrix (ECM) detachment and inhibits anoikis-resistance-induced PCa cell invasion and migration as well as epithelial-mesenchymal transition (EMT) process. TUBB3 knockdown significantly reduces αvß3/FAK/Src axis activation, blocking its downstream oncogenic signaling. In addition, we develop bone-targeting lipid nanoparticles (BT-LNP) based on bisphosphonate-modified ionizable lipid for systemic delivery of siRNA targeting TUBB3 (siTUBB3). BT-LNP-delivered siTUBB3 therapy with localization in the bone microenvironment significantly attenuate PCa bone metastasis progression in vivo upon intravenous administration. These findings pinpoint that TUBB3, as a key regulator of anoikis resistance, is an effective therapeutic target in bone metastatic PCa and that BT-LNP-mediated systemic delivery of siTUBB3 can be developed as a novel therapeutic strategy for this disease. This article is protected by copyright. All rights reserved.

12.
Neurobiol Dis ; 197: 106534, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38759931

ABSTRACT

Amyotrophic lateral sclerosis (ALS) is one of the most common neurodegenerative diseases, yet effective treatment is lacking. Moreover, the underlying pathomechanisms of ALS remain unclear, with impaired mitophagy function being increasingly recognized as a contributing factor. FUN14 domain-containing protein 1 (FUNDC1) is an autophagy receptor localized to the outer mitochondrial membrane and a mitochondrial membrane protein that mediates mitophagy and therefore considered as important factor in neurodegenerative diseases. However, its specific role in ALS is not yet clear. Therefore, this study aimed to investigate the regulatory role of FUNDC1 in ALS and determine its regulatory mechanisms. ALS transgenic mice were obtained and maintained under standard conditions. Cell lines were generated by stable transfection with hSOD1G93A or control vectors. Mice received intrathecal injections of AAV9 vectors expressing FUNDC1 or EGFP. Motor function was assessed through behavioral tests, and histological and immunostaining analyses were performed. Colocalization analysis was conducted in transfected cells, and protein expression was evaluated via western blotting. We first observed that FUNDC1 was significantly downregulated in the spinal cord tissues of SOD1G93A mice. FUNDC1 overexpression considerably improved locomotor activity and prolonged survival time in SOD1G93A mice. Mechanistically, reduced expression of FUNDC1 resulted in decreased mitophagy, as indicated by decreased recruitment through LC3 in SOD1G93A mice and cellular models. Consequently, this led to increased mitochondrial accumulation and cell apoptosis, exacerbating the ALS phenotype. Furthermore, we identified transcription factor FOXD3 as an essential upstream factor of FUNDC1, resulting in reduced transcription of FUNDC1 in ALS lesions. This study suggests a novel strategy of targeting FUNDC1-mediated mitophagy for developing therapeutic interventions to mitigate disease progression and improve outcomes for ALS patients.

13.
Orthop Surg ; 16(6): 1434-1444, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38693602

ABSTRACT

OBJECTIVE: The volume based procurement (VBP) program in China was initiated in 2022. The cost-effectiveness of robotic arm assisted total knee arthroplasty is yet uncertain after the initiation of the program. The objective of the study was to investigate the cost-effectiveness of robotic arm-assisted total knee arthroplasty and the influence of the VBP program to its cost-effectiveness in China. METHODS: The study was a Markov model-based cost-effectiveness study. Cases of primary total knee arthroplasty from January 2019 to December 2021 were included retrospectively. A Markov model was developed to simulate patients with advanced knee osteoarthritis. Manual and robotic arm-assisted total knee arthroplasties were compared for cost-effectiveness before and after the engagement of the VBP program in China. Probability and sensitivity analysis were conducted. RESULTS: Robotic arm-assisted total knee arthroplasty showed better recovery and lower revision rates before and after initiation of the VBP program. Robotic arm-based TKA was superior to manual total knee arthroplasty, with an increased effectiveness of 0.26 (16.87 vs 16.61) before and 0.52 (16.96 vs 16.43) after the application of Volume-based procurement, respectively. The procedure is more cost-effective in the new procurement system (17.13 vs 16.89). Costs of manual or robotic arm-assisted TKA were the most sensitive parameters in our model. CONCLUSION: Based on previous and current medical charging systems in China, robotic arm-assisted total knee arthroplasty is a more cost-effective procedure compared to traditional manual total knee arthroplasty. As the volume-based procurement VBP program shows, the procedure can be more cost-effective.


Subject(s)
Arthroplasty, Replacement, Knee , Cost-Benefit Analysis , Markov Chains , Robotic Surgical Procedures , Humans , Arthroplasty, Replacement, Knee/economics , Arthroplasty, Replacement, Knee/methods , China , Robotic Surgical Procedures/economics , Robotic Surgical Procedures/methods , Retrospective Studies , Female , Middle Aged , Male , Aged , Osteoarthritis, Knee/surgery , Osteoarthritis, Knee/economics
14.
Oncol Lett ; 28(1): 329, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38807675

ABSTRACT

Pheochromocytoma is a tumor of the sympathetic nervous system, characterized by atypical symptoms and signs. Pheochromocytoma metastases can be found in various tissues and organs. However, synchronous metastasis at the initial diagnosis of pheochromocytoma is rare. The present study described a case with synchronous liver metastasis at the initial diagnosis of adrenal pheochromocytoma based on imaging findings. A 41-year-old woman presented with liver pain and fatigue for 1 month. Physical examination showed increased blood pressure and heart rate with sinus tachycardia. Laboratory examination revealed normal levels of liver tumor markers and increased levels of serum or urine epinephrine and norepinephrine. CT examination revealed a large cystic solid mass in the right lobe of the liver and right adrenal gland, and the solid part of the mass was enhanced after enhancement. The pathological diagnosis was pheochromocytoma of the right adrenal gland with liver metastasis. The patient underwent right hepatectomy and right adrenal tumor resection. During the postoperative follow-up, the patient's blood pressure and catecholamine levels were within the normal range. Three years after surgery, the CT examination revealed multiple liver metastases. Chemotherapy was administered to the patient. A year later, re-examination revealed an increase and enlargement of the metastases, and the mass of the right adrenal gland remained similar to the previous one. After 6 months of follow-up, the patient succumbed to recurrence and metastasis. Preoperative diagnosis of metastatic pheochromocytoma is challenging. This case mainly emphasizes that imaging findings can help the clinical diagnosis of metastatic pheochromocytoma.

15.
BJU Int ; 2024 May 31.
Article in English | MEDLINE | ID: mdl-38817129

ABSTRACT

OBJECTIVE: To evaluate the effect of a new strategy of transperineal anastomotic urethroplasty (TAU) with proximal transection in treating pelvic fracture urethral injury (PFUI) associated with urethrorectal fistula (URF). PATIENTS AND METHODS: A retrospective review of all patients treated by TAU with proximal transection and fistula repair for PFUI associated with URF was performed between August 2013 and July 2022. Information on demographics, peri-operative variables, and postoperative follow-up outcomes was collected. Successful surgery was defined as restoration of a uniform urethral calibre using flexible cystoscopy (third postoperative month) without strictures or leakage, with no further interventions required. Functional outcomes, including erectile function (assessed using the five-item International Index of Erectile Function) and urinary continence, were assessed. RESULTS: Forty patients diagnosed with PFUI associated with URF and treated by TAU with proximal transection and rectal fistula repair were enrolled. Six patients (15.0%) had a history of failed urethral reconstruction. The mean stenosis length and fistula diameter were 2.9 cm and 1.2 cm, respectively. All patients underwent faecal diversion before urethroplasty. After a median (range) follow-up of 45 (3-115) months, the final success rate was 90.0% (36/40). Postoperative complications included haematoma in three patients, epididymo-orchitis in three, wound infection in one, wound bleeding in one, delayed wound healing in three, and wound numbness in three. The overall incidence of postoperative erectile dysfunction reached 75.0%, with a median (range) score of 9 (0-19). Normal continence was achieved in 31 patients (77.5%). Occasional incontinence without the need for urinal pads occurred in eight patients, whereas one patient required urinal pads. CONCLUSIONS: Transperineal anastomotic urethroplasty with proximal transection is a precise and effective surgical strategy for treating PFUI associated with URF. This strategy ensures a high success rate and improves surgical efficiency.

16.
Int J Biol Macromol ; 271(Pt 1): 132437, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38761910

ABSTRACT

Colletotrichum fructicola is a globally significant phytopathogenic fungus. Mycovirus-induced hypovirulence has great potential for biological control and study of fungal pathogenic mechanisms. We previously reported that the mycovirus Colletotrichum alienum partitivirus 1 (CaPV1) is associated with the hypovirulence of C. fructicola, and the present study aimed to further investigate a host factor and its roles in mycovirus-induced hypovirulence. A gene named CfKOB1, which encodes putative protein homologous to the ß-subunit of voltage-gated potassium channels and aldo-keto reductase, is downregulated upon CaPV1 infection and significantly upregulated during the early infection phase of Nicotiana benthamiana by C. fructicola. Deleting the CfKOB1 gene resulted in diminished vegetative growth, decreased production of asexual spores, hindered appressorium formation, reduced virulence, and altered tolerance to abiotic stresses. Transcriptome analysis revealed that CfKOB1 regulates many metabolic pathways as well as the cell cycle and apoptosis. Furthermore, enhanced apoptosis was observed in the ΔCfKOB1 mutants. Viral RNA accumulation was significantly increased in the CfKOB1 deletion mutant. Additionally, our findings demonstrated that CaPV1 infection in the WT strain also induced cell apoptosis. Collectively, these results highlight the diverse biological roles of the CfKOB1 gene in the fungus C. fructicola, while it also participates in mycovirus-induced hypovirulence by regulating apoptosis.

17.
Front Pediatr ; 12: 1388921, 2024.
Article in English | MEDLINE | ID: mdl-38725987

ABSTRACT

Objectives: To develop a predictive model for patent ductus arteriosus (PDA) in preterm infants at seven days postpartum. The model employs ultrasound measurements of the ductus arteriosus (DA) intimal thickness (IT) obtained within 24 h after birth. Methods: One hundred and five preterm infants with gestational ages ranging from 27.0 to 36.7 weeks admitted within 24 h following birth were prospectively enrolled. Echocardiographic assessments were performed to measure DA IT within 24 h after birth, and DA status was evaluated through echocardiography on the seventh day postpartum. Potential predictors were considered, including traditional clinical risk factors, M-mode ultrasound parameters, lumen diameter of the DA (LD), and DA flow metrics. A final prediction model was formulated through bidirectional stepwise regression analysis and subsequently subjected to internal validation. The model's discriminative ability, calibration, and clinical applicability were also assessed. Results: The final predictive model included birth weight, application of mechanical ventilation, left ventricular end-diastolic diameter (LVEDd), LD, and the logarithm of IT (logIT). The receiver operating characteristic (ROC) curve for the model, predicated on logIT, exhibited excellent discriminative power with an area under the curve (AUC) of 0.985 (95% CI: 0.966-1.000), sensitivity of 1.000, and specificity of 0.909. Moreover, the model demonstrated robust calibration and goodness-of-fit (χ2 value = 0.560, p > 0.05), as well as strong reproducibility (accuracy: 0.935, Kappa: 0.773), as evidenced by 10-fold cross-validation. A decision curve analysis confirmed the model's broad clinical utility. Conclusions: Our study successfully establishes a predictive model for PDA in preterm infants at seven days postpartum, leveraging the measurement of DA IT. This model enables identifying, within the first 24 h of life, infants who are likely to benefit from timely DA closure, thereby informing treatment decisions.

18.
Transl Res ; 2024 May 28.
Article in English | MEDLINE | ID: mdl-38815898

ABSTRACT

HCC is a malignancy characterized by high incidence and mortality rates. Traditional classifications of HCC primarily rely on tumor morphology, phenotype, and multicellular molecular levels, which may not accurately capture the cellular heterogeneity within the tumor. Current research on HCC using scRNA-seq is predominantly focused on immune and stromal cells. This study integrates scRNA-seq and bulk RNA-seq to spotlight HP as a critical gene. HP is highly expressed in HCC malignant cells and lowly expressed in T cells. Within malignant cells, elevated HP expression interacts with C3, promoting Th1-type responses via the C3/C3AR1 axis. In T cells, down-regulating HP expression favors the expression of Th1 cell-associated marker genes, potentially enhancing Th1-type responses. Consequently, we developed a "HP-promoted Th1 response reclassification" gene set, correlating higher activity scores with improved survival rates in HCC patients. Additionally, four predictive models for neoadjuvant treatment based on HP and C3 expression were established: 1) Low HP and C3 expression with high Th2 cell infiltration; 2) High HP and low C3 expression with high Th2 cell infiltration; 3) High HP and C3 expression with high Th1 cell infiltration; 4) Low HP and high C3 expression with high Th1 cell infiltration. In conclusion, the HP gene selected from the HCC malignant cell subgroup (Malignant_Sub 6) might serve as a potential ally against the tumor by promoting Th1-type immune responses. The establishment of the "HP-promoted Th1 response reclassification" gene set offers predictive insights for HCC patient survival prognosis and neoadjuvant treatment efficacy, providing directions for clinical treatments.

19.
Opt Express ; 32(6): 8638-8656, 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38571118

ABSTRACT

The laser-induced damage of ultraviolet fused silica optics is a critical factor that limits the performance enhancement of high-power laser facility. Currently, wet etching technology based on hydrofluoric acid (HF) can effectively eliminate absorbing impurities and subsurface defects, thereby significantly enhancing the damage resistance of fused silica optics. However, with an increase in the operating fluence, the redeposition defects generated during wet etching gradually become the primary bottleneck that restricts its performance improvement. The composition and morphology of redeposition defects were initially identified in this study, followed by an elucidation of their formation mechanism. A mitigation strategy was then proposed, which combines a reduction in the generation of precipitation with an acceleration of the precipitation dissolution process. Additionally, we systematically investigated the influence of various process parameters such as extrinsic impurity, etching depth, and megasonic excitation on the mitigation of deposition defects. Furthermore, a novel multiple-step dynamic etching method was developed. Through comprehensive characterization techniques, it has been confirmed that this new etching process not only effectively mitigate redeposition defects under low fluence conditions but also exhibits significant inhibition effects on high fluence precursors. Consequently, it significantly enhances the laser damage resistance performance of fused silica optics.

20.
Phys Med Biol ; 69(10)2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38593827

ABSTRACT

Objective.To address the challenge of meningioma grading, this study aims to investigate the potential value of peritumoral edema (PTE) regions and proposes a unique approach that integrates radiomics and deep learning techniques.Approach.The primary focus is on developing a transfer learning-based meningioma feature extraction model (MFEM) that leverages both vision transformer (ViT) and convolutional neural network (CNN) architectures. Additionally, the study explores the significance of the PTE region in enhancing the grading process.Main results.The proposed method demonstrates excellent grading accuracy and robustness on a dataset of 98 meningioma patients. It achieves an accuracy of 92.86%, precision of 93.44%, sensitivity of 95%, and specificity of 89.47%.Significance.This study provides valuable insights into preoperative meningioma grading by introducing an innovative method that combines radiomics and deep learning techniques. The approach not only enhances accuracy but also reduces observer subjectivity, thereby contributing to improved clinical decision-making processes.


Subject(s)
Deep Learning , Image Processing, Computer-Assisted , Meningioma , Neoplasm Grading , Meningioma/diagnostic imaging , Meningioma/pathology , Humans , Image Processing, Computer-Assisted/methods , Edema/diagnostic imaging , Meningeal Neoplasms/diagnostic imaging , Meningeal Neoplasms/pathology , Radiomics
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