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BACKGROUND: Chinese cherry [Cerasus pseudocerasus (Lindl.) G.Don] (syn. Prunus pseudocerasus Lindl.) is an economically important fruiting cherry species with a diverse range of attractive colors, spanning from the lightest yellow to the darkest black purple. However, the MYB transcription factors involved in anthocyanin biosynthesis underlying fruit color variation in Chinese cherry remain unknown. RESULTS: In this study, we characterized the R2R3-MYB gene family of Chinese cherry by genome-wide identification and compared it with those of 10 Rosaceae relatives and Arabidopsis thaliana. A total of 1490 R2R3-MYBs were classified into 43 subfamilies, which included 29 subfamilies containing both Rosaceae MYBs and AtMYBs. One subfamily (S45) contained only Rosaceae MYBs, while three subfamilies (S12, S75, and S77) contained only AtMYBs. The variation in gene numbers within identical subfamilies among different species and the absence of certain subfamilies in some species indicated the species-specific expansion within MYB gene family in Chinese cherry and its relatives. Segmental and tandem duplication events primarily contributed to the expansion of Chinese cherry R2R3-CpMYBs. The duplicated gene pairs underwent purifying selection during evolution after duplication events. Phylogenetic relationships and transcript profiling revealed that CpMYB10 and CpMYB4 are involved in the regulation of anthocyanin biosynthesis in Chinese cherry fruits. Expression patterns, transient overexpression and VIGS results confirmed that CpMYB10 promotes anthocyanin accumulation in the fruit skin, while CpMYB4 acts as a repressor, inhibiting anthocyanin biosynthesis of Chinese cherry. CONCLUSIONS: This study provides a comprehensive and systematic analysis of R2R3-MYB gene family in Chinese cherry and Rosaceae relatives, and identifies two regulators, CpMYB10 and CpMYB4, involved in anthocyanin biosynthesis in Chinese cherry. These results help to develop and utilize the potential functions of anthocyanins in Chinese cherry.
Subject(s)
Anthocyanins , Multigene Family , Phylogeny , Transcription Factors , Anthocyanins/biosynthesis , Transcription Factors/genetics , Transcription Factors/metabolism , Gene Expression Regulation, Plant , Plant Proteins/genetics , Plant Proteins/metabolism , Prunus avium/genetics , Prunus avium/metabolism , Genome, Plant , Arabidopsis/genetics , Arabidopsis/metabolism , Fruit/genetics , Fruit/metabolismABSTRACT
Background: Vulnerable carotid plaque is closely associated with ischemic stroke. Contrast-enhanced ultrasound (CEUS) and high-resolution magnetic resonance imaging (HR-MRI) are two imaging modalities capable of assessing the vulnerability of carotid plaques. This systematic review aimed to compare the diagnostic performance of CEUS and HR-MRI in the evaluation of histologically defined vulnerable carotid plaques. Methods: A systematic literature search with predefined search terms was performed on PubMed, the Cochrane library, Embase, and Web of Science from January 2001 to December 2023. Studies that evaluated the diagnostic accuracy of vulnerable carotid plaques confirmed by histology with CEUS and/or HR-MRI were included. The pooled values were calculated using a random-effects meta-analysis to determine diagnostic power. Results: This analysis included a total of 839 patients from 20 studies comprising 1,357 HR-MRI plaques and CEUS 504 plaques. With the reference to histological results, all nine CEUS studies focused on the detection of intraplaque neovascularization (IPN), and three studies also examined morphological changes or ulcerated plaques; meanwhile, among the HR-MRI studies, seven predominantly focused on identifying intraplaque hemorrhage (IPH) and three mainly examined lipid-rich necrotic cores (LRNCs). The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and the area under the curve (AUC) for CEUS studies were 0.85 [95% confidence interval (CI): 0.81-0.89], 0.76 (95% CI: 0.69-0.83), 3.41 (95% CI: 1.68-6.94), 0.14 (95% CI: 0.05-0.38), 27.68 (95% CI: 5.78-132.62), and 0.89 [standard error (SE) 0.06], respectively; for HR-MRI, these values were 0.88 (95% CI: 0.85-0.90), 0.89 (95% CI: 0.86-0.92), 7.49 (95% CI: 3.28-17.09), 0.17 (95% CI: 0.12-0.24), 49.13 (95% CI: 23.87-101.11), and 0.94 (SE 0.01), respectively. The difference in AUC between the two modalities was not statistically significant (Z=0.82; P=0.68). Conclusions: CEUS and HR-MRI are valuable noninvasive diagnostic tools for identifying histologically confirmed vulnerable carotid plaques and demonstrate similar diagnostic performance. CEUS is more capable of detecting IPN and morphological changes, while HR-MRI is more suited to classifying IPH and LRNCs.
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BACKGROUND: Sirolimus is increasingly utilized in treating diseases associated with mTOR pathway overactivation. Despite its potential, the lack of evidence regarding its long-term safety across all age groups, particularly in pediatric patients, has limited its further application. This study aims to assess the long-term safety of sirolimus, with a specific focus on its impact on growth patterns in pediatric patients. METHODS: This pooled analysis inlcudes two prospective cohort studies spanning 10 years, including 1,738 participants (aged 5 days to 69 years) diagnosed with tuberous sclerosis and/or lymphangioleiomyomatosis. All participants were mTOR inhibitor-naive and received 1 mg/m²/day of sirolimus, with dose adjustments during a two-week titration period to maintain trough blood concentrations between 5 and 10 ng/ml (maximum dose 2 mg). Indicators of physical growth, hematopoietic, liver, renal function, and blood lipid levels were all primary outcomes and were analyzed. The adverse events and related management were also recorded. RESULTS: Sirolimus administration did not lead to deviations from normal growth ranges, but higher doses exhibited a positive association with Z-scores exceeding 2 SD in height, weight, and BMI. Transient elevations in red blood cell and white blood cell counts, along with hyperlipidemia, were primarily observed within the first year of treatment. Other measured parameters remained largely unchanged, displaying only weak correlations with drug use. Stomatitis is the most common adverse event (920/1738, 52.9%). In adult females, menstrual disorders were observed in 48.5% (112/217). CONCLUSIONS: Sirolimus's long-term administration is not associated with adverse effects on children's physical growth pattern, nor significant alterations in hematopoietic, liver, renal function, or lipid levels. A potential dose-dependent influence on growth merits further exploration. TRIAL REGISTRATION: Pediatric patients: Chinese clinical trial registry, No. ChiCTR-OOB-15,006,535. Adult patients: ClinicalTrials, No. NCT03193892.
Subject(s)
Sirolimus , Humans , Sirolimus/adverse effects , Sirolimus/therapeutic use , Child , Female , Adolescent , Child, Preschool , Adult , Male , Infant , Young Adult , Middle Aged , Infant, Newborn , Aged , Tuberous Sclerosis/drug therapy , Lymphangioleiomyomatosis/drug therapy , Prospective StudiesABSTRACT
Endometrial organoids offer valuable insights into the development and pathophysiology of endometrial diseases and serve as platforms for drug testing. While human and mouse endometrial organoids have been developed, research on rat endometrial organoids remains limited. Given that rats can better simulate certain endometrial pathologies, such as intrauterine adhesions, this study aimed to establish rat endometrial organoids. We present a detailed protocol for the isolation and culture of rat endometrial epithelial stem cells (reESCs) and the generation of rat endometrial organoids. Using a refined reESCs expansion medium, we successfully isolated and stably expanded reESCs, demonstrating their long-term culture potential. The reESC-generated organoids exhibited typical structural and functional characteristics of the endometrium, including hormone responsiveness. Our results showed that rat endometrial organoids could be cultured over a long term with stable proliferation, maintaining the glandular structure, cell polarity, and functional characteristics of the endometrial epithelium. This novel rat-derived endometrial organoid model provides a valuable platform for studying endometrial diseases and testing therapeutic interventions, with potential applications across various mammalian species.
Subject(s)
Endometrium , Epithelial Cells , Organoids , Animals , Female , Organoids/cytology , Rats , Endometrium/cytology , Epithelial Cells/cytology , Stem Cells/cytology , Uterus/cytologyABSTRACT
With their fascinating properties, emerging two-dimensional (2D) materials offer innovative ways to prepare high-performance infrared (IR) detectors. However, the current performance of 2D IR photodetectors is still below the requirements for practical application owing to the severe interfacial recombination, sharply raised contact resistance, and deteriorated metal conductivity at nanoscale. Here, we introduce a vertical barrier heterojunction with a structure of PtSe2/GaAs that combines the excellent optoelectronic properties of transition metal sulfides with topological semi-metals, which allows for an adjustable bandgap and high carrier mobility. The heterojunction was fabricated using the wet transfer method. The heterostructures show significant rectification behaviors and photovoltaic effects, which allow it to operate as a self-driven photodetector at zero bias. The photoresponse parameters at 850 nm with zero bias voltage are 67.2 mA W-1, 6.7 × 1012 Jones, 9.8%, 3.8 × 105, 164 µs, and 198 µs for the responsivity, specific detectivity, external quantum efficiency, Ilight/Idark ratio, rise time, and fall time, respectively. Moreover, the heterojunction is highly sensitive to a wide spectral band from ultraviolet to near-infrared (360-1550 nm). At the same time, this heterostructure demonstrates significant potential for applications in IR polarized light detection and room-temperature high-resolution IR imaging. The excellent properties of the heterojunction make it well-suited for high-performance, self-powered IR detection.
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BACKGROUND: Cushing's syndrome (CS) is associated with increased risk for heart failure, which often initially manifests as left ventricular diastolic dysfunction (LVDD). In this study, we aimed to explore the potential risk factors of LVDD in CS by incorporating body composition parameters. METHODS: A retrospective study was conducted on patients diagnosed with endogenous CS no less than 18 years old. The control group consisted of healthy individuals who were matched to CS patients in terms of gender, age, and BMI. LIFEx software (version 7.3) was applied to measure epicardial adipose tissue volume (EATV) on non-contrast chest CT, as well as abdominal adipose tissue and skeletal muscle mass at the first lumbar vertebral level. Echocardiography was used to evaluate left ventricular (LV) diastolic function. Body compositions and clinical data were examined in relation to early LVDD. RESULTS: A total of 86 CS patients and 86 healthy controls were enrolled. EATV was significantly higher in CS patients compared to control subjects (150.33 cm3 [125.67, 189.41] vs 90.55 cm3 [66.80, 119.84], p < 0.001). CS patients had noticeably increased visceral fat but decreased skeletal muscle in comparison to their healthy counterparts. Higher prevalence of LVDD was found in CS patients based on LV diastolic function evaluated by E/A ratio (p < 0.001). EATV was proved to be an independent risk factor for LVDD in CS patients (OR = 1.015, 95%CI 1.003-1.026, p = 0.011). If the cut-point of EATV was set as 139.252 cm3 in CS patients, the diagnostic sensitivity and specificity of LVDD were 84.00% and 55.60%, respectively. CONCLUSION: CS was associated with marked accumulation of EAT and visceral fat, reduced skeletal muscle mass, and increased prevalence of LVDD. EATV was an independent risk factor for LVDD, suggesting the potential role of EAT in the development of LVDD in CS.
This study explored the potential risk factors of LVDD in endogenous CS by incorporating body composition parameters. EATV was identified as an independent risk factor for LVDD. Targeted therapeutic interventions to reduce excessive cortisol-induced EAT accumulation may be promising to mitigate the risk of LVDD development in patients with CS.
Subject(s)
Adipose Tissue , Cushing Syndrome , Echocardiography , Pericardium , Ventricular Dysfunction, Left , Humans , Male , Cushing Syndrome/physiopathology , Cushing Syndrome/complications , Cushing Syndrome/epidemiology , Female , Retrospective Studies , Adult , Ventricular Dysfunction, Left/physiopathology , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/epidemiology , Ventricular Dysfunction, Left/etiology , Pericardium/diagnostic imaging , Adipose Tissue/diagnostic imaging , Adipose Tissue/physiopathology , Middle Aged , Diastole , Risk Factors , Case-Control Studies , Tomography, X-Ray Computed , Epicardial Adipose TissueABSTRACT
Esculetin (ESC) is a coumarin-derived phytochemical prevalent in traditional Chinese medicine that exhibits anti-acute ischemic stroke activities. Our previous studies demonstrate that CKLF1 is a potential anti-stroke target for coumarin-derived compound. In this study we investigated whether CKLF1 was involved in the neuroprotective effects of ESC against photothrombotic stroke in mice. The mice were treated with ESC (20, 40 or 80 mg·kg-1·d-1, i.g.) for two weeks. The therapeutic effect of ESC was assessed using MRI, neurological function evaluation, and a range of behavioral tests on D1, 3, 7 and 14 of ESC administration. We showed that oral administration of ESC dose-dependently reduced the cerebral infarction volume within one week after stroke, improved behavioral performance, and alleviated neuropathological damage within two weeks. Functional MRI revealed that ESC significantly enhanced the abnormal low-frequency fluctuation (ALFF) value of the motor cortex and promoted functional connectivity between the supplementary motor area (SMA) and multiple brain regions. We demonstrated that ESC significantly reduced the protein levels of CKLF1 and CCR5, as well as the CKLF1/CCR5 protein complex in the peri-infarcted area. We showed that ESC (0.1-10 µM) dose-dependently blocked CKLF1-induced chemotactic movement of neutrophils in the Transwell assay, reducing the interaction of CKLF1/CCR5 on the surface of neutrophils, thereby reducing neutrophil infiltration, and decreasing the expression of ICAM-1, VCAM-1 and MMP-9 in the peri-infarct tissue. Knockout of CKLF1 reduced brain infarction volume and motor dysfunction after stroke but also negated the anti-stroke efficacy and neutrophil infiltration of ESC. These results suggest that the efficacy of ESC in promoting post-stroke neural repair depends on its inhibition on CKLF1-mediated neutrophil infiltration, which offering novel perspectives for elucidating the therapeutic properties of coumarins.
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Background: Brain lymphatic drainage impairment is a prevalent characteristic in both aging and neurodegeneration. Surgery is more likely to induce excessive neuroinflammation and postoperative neurocognitive disorder (PND) among patients with aging and neurodegeneration. We hypothesized that surgical trauma may aggravate PND through preexisting cerebral lymphatic drainage impairment. However, there remains limited understanding about the role of surgery in changes of neurocognitive function in the populations with preoperative brain lymphatic drainage impairment. This study aims to expand our insight into surgery-induced glymphatic dysfunction, neuroinflammation and PND in middle-aged mice with preoperative brain lymphatic drainage impairment. Materials and methods: Deep cervical lymph nodes ligation (LdcLNs) was performed on middle-aged mice to establish preoperative brain lymphatic drainage impairment. A month later, laparotomy was performed on these mice with or without LdcLNs followed by analysis of brain neuroinflammation, glymphatic function, neuronal damage, and behavioral test. Results: LdcLNs disrupted meningeal lymphatic drainage. In middle-aged mice with LdcLNs, surgery exacerbated more serious glymphatic dysfunction accompanied by aggravation of A1 astrocytes activation and AQP4 depolarization. Furthermore, surgery caused neuronal damage via reducing expression of neuronal nuclei (NeuN), post-synaptic density protein 95 (PSD95) and synaptophysin (SYP), as well as impairment in exploratory behavior and spatial working memory in middle-aged mice with LdcLNs. Additionally, surgery induced neuroinflammation with elevated microglia activation and increased the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6, as well as activated more expression of HMGB1/TLR-4/NF-κB pathway in middle-aged mice with LdcLNs. Conclusion: Surgery exacerbates neuroinflammation and glymphatic dysfunction, ultimately resulting in neuronal damage and neurocognitive disorder in middle-aged mice with preoperative brain lymphatic drainage impairment. These results suggest that brain lymphatic drainage impairment may be a deteriorating factor in the progression of PND, and restoring its function may serve as a potential strategy against PND.
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Osteoporotic femoral neck fractures (OFNFs) pose a significant orthopedic challenge in the elderly population, accounting for up to 40% of all osteoporotic fractures and leading to considerable health deterioration and increased mortality. In addressing the critical need for early identification of osteoporosis through routine screening of femoral neck bone mineral density (FNBMD), this study developed a user-friendly prediction model aimed at men aged 50 years and older, a demographic often overlooked in osteoporosis screening. Utilizing data from the National Health and Nutrition Examination Survey (NHANES), the study involved outlier detection and handling, missing value imputation via the K nearest neighbor (KNN) algorithm, and data normalization and encoding. The dataset was split into training and test sets with a 7:3 ratio, followed by feature screening through the least absolute shrinkage and selection operator (LASSO) and the Boruta algorithm. Eight different machine learning algorithms were then employed to construct predictive models, with their performance evaluated through a comprehensive metric suite. The random forest regressor (RFR) emerged as the most effective model, characterized by key predictors such as age, body mass index (BMI), poverty income ratio (PIR), serum calcium, and race, achieving a coefficient of determination (R²) of 0.218 and maintaining robustness in sensitivity analyses. Notably, excluding race from the model resulted in sustained high performance, underscoring the model's adaptability. Interpretations using Shapley additive explanations (SHAP) highlighted the influence of each feature on FNBMD. These findings indicate that our predictive model effectively aids in the early detection of osteoporosis, potentially reducing the incidence of OFNFs in this high-risk population.
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BACKGROUND: Obstructive sleep apnea hypoventilation syndrome (OSAHS) in children is a sleep respiratory disorder characterized by a series of pathophysiologic changes. Statistics in recent years have demonstrated an increasing yearly incidence. AIM: To investigate the risk factors for OSAHS in children and propose appropriate management measures. METHODS: This study had a case-control study design. Altogether, 85 children with OSAHS comprised the case group, and healthy children of the same age and sex were matched at 1:1 as the control group. Basic information, including age, sex, height, weight and family history, and medical history data of all study participants were collected. Polysomnography was used to detect at least 8 h of nocturnal sleep. All participants were clinically examined for the presence of adenoids, enlarged tonsils, sinusitis, and rhinitis. RESULTS: The analysis of variance revealed that the case group had a higher proportion of factors such as adenoid grading, tonsil indexing, sinusitis, and rhinitis than the control group. CONCLUSION: A regression model was established, and glandular pattern grading, tonsil indexing, sinusitis, and pharyngitis were identified as independent risk factors affecting OSAHS development.
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BACKGROUND: Cassava is one of three major potato crops and the sixth most important food crop globally. Improving yield remains a primary aim in cassava breeding. Notably, plant height significantly impacts the yield and quality of crops; however, the mechanisms underlying cassava plant height development are yet to be elucidated. RESULTS: In this study, we investigated the mechanisms responsible for cassava plant height development using phenotypic, anatomical, and transcriptomic analyses. Phenotypic and anatomical analysis revealed that compared to the high-stem cassava cultivar, the dwarf-stem cassava cultivar exhibited a significant reduction in plant height and a notable increase in internode tissue xylem area. Meanwhile, physiological analysis demonstrated that the lignin content of dwarf cassava was significantly higher than that of high cassava. Notably, transcriptome analysis of internode tissues identified several differentially expressed genes involved in cell wall synthesis and expansion, plant hormone signal transduction, phenylpropanoid biosynthesis, and flavonoid biosynthesis between the two cassava cultivars. CONCLUSIONS: Our findings suggest that internode tissue cell division, secondary wall lignification, and hormone-related gene expression play important roles in cassava plant height development. Ultimately, this study provides new insights into the mechanisms of plant height morphogenesis in cassava and identifies candidate regulatory genes associated with plant height that can serve as valuable genetic resources for future crop dwarfing breeding.
Subject(s)
Gene Expression Profiling , Gene Expression Regulation, Plant , Manihot , Manihot/genetics , Manihot/growth & development , Manihot/metabolism , Phenotype , Transcriptome , Lignin/metabolism , Lignin/biosynthesisABSTRACT
OBJECTIVES: This review aims to comprehensively summarize the differences in anticholinergic drug burden (ADB) scores between older hospitalized patients with and without delirium. METHODS: We searched PubMed, Embase, Web of Science, Cochrane Library and CINAHL EBSCOhost databases to identify prospective cohort studies exploring the relationship between ADB and the occurrence of delirium in older hospitalized patients. The primary outcome of the review was the mean ADB scores for the delirium and non-delirium groups, and the secondary outcome was the scores for the subsyndromal and non-delirium groups. The standardized mean difference (SMD) and corresponding 95% confidence intervals (95% CI) were incorporated using a fixed-effect method. Moreover, we performed subgroup analysis according to the admission type, age, the ADB scale type and the ADB classification. RESULTS: Nine prospective cohort studies involving 3791 older patients with a median age of 75.1 (71.6-83.9) were included. The ADB score was significantly higher in the delirium group than in the non-delirium group (SMD = 0.21, 95%CI 0.13-0.28). In subgroup analysis, the age subgroup was split into < 75 and ≥ 75 according to the median age of the older people. There were significant differences in ADB scores between older people with delirium and those without delirium in various subgroups: surgical (SMD = 0.20, 95%CI 0.12-0.28), internal medicine (SMD = 0.64, 95%CI 0.25-1.02), age < 75 (SMD = 0.17, 95%CI 0.08-0.26), age ≥ 75 (SMD = 0.27, 95%CI 0.15-0.39), ADS scale (SMD = 0.13, 95%CI 0.13-0.40), ARS scale (SMD = 0.15, 95%CI 0.03-0.26), ACB scale (SMD = 0.13, 95%CI 0.01-0.25), pre-admission ADB (SMD = 0.24, 95%CI 0.05-0.43) and ADB during hospitalization (SMD = 0.20, 95%CI 0.12-0.27). CONCLUSIONS: We found a quantitative relationship between ADB and delirium in older patients admitted for internal medicine and surgery. And this relationship remained significant in different age, ADB scale type and ADB classification subgroups. However, the actual difference in ADB scores between patients with delirium and without delirium was small. More high-quality observational studies should be conducted to explore the impact of ADB on delirium and subsyndromal delirium. CLINICAL TRIAL REGISTRATION: The protocol was published in the International Prospective Register of Systematic Reviews (PROSPERO) [Ref: CRD42022353649].
Subject(s)
Cholinergic Antagonists , Delirium , Hospitalization , Humans , Delirium/epidemiology , Cholinergic Antagonists/adverse effects , Cholinergic Antagonists/therapeutic use , Aged , Prospective Studies , Aged, 80 and over , Cohort StudiesABSTRACT
BACKGROUND: Candida parapsilosis has been implicated in central nervous system (CNS) infections (i.e., meningitis or ventriculitis) but has not been previously reported to cause intracerebral abscesses. CNS infections secondary to C. parapsilosis are notoriously difficult to treat due to the poor CNS penetration of amphotericin B. Historically, intraventricular amphotericin B has been used to treat C. parapsilosis ventriculitis. OBSERVATIONS: A 15-year-old female with no comorbidities presented with nonresolving headaches, photophobia, fevers, and meningism. Computed tomography (CT) of the brain revealed a right frontal abscess. After multiple drainage surgeries, subsequent CT scans showed reaccumulation of her abscess. C. parapsilosis was cultured, and the patient was then taken to the operating room where an external ventricular drain catheter was successfully placed within the abscess cavity. Pus was repeatedly aspirated, followed by the instillation of intralesional amphotericin B twice a day for 2 weeks. The patient's clinical condition improved substantially with complete resolution of symptoms, improvement of infective markers, and resolution of radiological features of the abscess. Follow-up of the patient revealed the absence of symptoms and image characteristics of abscess on CT 3 months posttreatment. LESSONS: Intralesional amphotericin B is a novel but effective treatment of C. parapsilosis intracerebral abscess, an organism not previously described as a cause of intracerebral abscesses. https://thejns.org/doi/10.3171/CASE2484.
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Glutathione S-transferases (GSTs) are multifunctional enzymes, and insect GSTs play a pivotal role in the metabolism of insecticides. Grapholita molesta is a worldwide pest that causes substantial economic losses to the fruit industry. However, it remains unclear how imidacloprid, a commonly used insecticide in orchards, is metabolized by G. molesta. In the present study, the synergist diethyl maleate (DEM), which inhibits the GST activity, exhibited a 22-fold synergistic ratio against imidacloprid. Two new GST genes, GmGSTD2 (OR096251) and GmGSTD3 (OR096252), were identified and successfully cloned, showing the highest expression in the Malpighian tubes. Knockdown of GmGSTD2 and GmGSTD3 by RNA interference, increased the mortality of G. molesta from 28% to 47% following imidacloprid treatment. Both recombinant GmGSTD2 and GmGSTD3 proteins exhibited 1-chloro-2,4-dinitrobenzene (CDNB) activity and could be inhibited by imidacloprid in vitro, with maximum inhibition was 60% for GmGSTD2 and 80% for GmGSTD3. These results suggested that GSTs participate in the metabolism of imidacloprid with GmGSTD2 and GmGSTD3 playing key roles in this process.
Subject(s)
Glutathione Transferase , Insecticides , Neonicotinoids , Nitro Compounds , Neonicotinoids/metabolism , Nitro Compounds/metabolism , Insecticides/metabolism , Glutathione Transferase/metabolism , Glutathione Transferase/genetics , Animals , Insect Proteins/genetics , Insect Proteins/metabolism , Imidazoles/metabolismABSTRACT
BACKGROUND: Monolithic or semi-monolithic detectors are attractive for positron emission tomography (PET) scanners with depth-of-interaction (DOI) capability. However, they often require complicated calibrations to determine the interaction positions of gamma photons. PURPOSE: We introduce a novel hybrid detector design that combines pixelated and semi-monolithic elements to achieve DOI capability while simplifying the calibrations for positioning. METHODS: A prototype detector with eight hybrid lutetium-yttrium oxyorthosilicate (LYSO) layers having dimensions of 25.8 × 12.9 × 15 mm3 was constructed. The energy-weighted and energy-squared weighted averages were used for estimating the x- (pixelated direction) and y-positions (non-pixelated direction). Pseudo-pixels were defined as discrete areas on the flood image based on the crystal look-up table (LUT). The intrinsic spatial resolutions in the pixelated and non-pixelated directions were measured. The ratio of the maximum to the sum of the multipixel photon counter (MPPC) signals was used to estimate the DOI positions. The coincidence timing resolution (CTR) was measured using the average and energy-weighted average of the earliest n time stamps. Two energy windows of 250-700 and 400-600 keV were applied for the measurements. RESULTS: The pattern of the flood images showed discrete event clusters, demonstrating that simple calibrations for determining the x- and y-positions of events could be achieved. Under 400-600 keV energy window, the average intrinsic spatial resolutions were 1.15 and 1.34 mm for the pixelated and non-pixelated directions; the average DOI resolution of the second row of pseudo-pixels was 5.1 mm in full width at half maximum (FWHM); when using the energy-weighted average of the earliest four-time stamps, the best CTR of 350 ps was achieved. Applying a broader energy window of 250-700 keV only slightly degrades the DOI resolution while maintaining the intrinsic resolution; the best CTR degrades to 410 ps. CONCLUSIONS: The proposed hybrid detector concept was verified, and a prototype detector showed high performance for 3D positioning and timing resolution. The novel detector concept shows promise for preclinical and clinical PET scanners with DOI capability.
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Fibrous supercapacitors (SCs) are emerging promising power sources for flexible/wearable electronics and have attracted an extensive amount of attention from researchers. However, the low energy density has always hindered their further development. Here, a coaxial fibrous SC (CFSC) was fabricated by one-step wet-spinning combined with an electrodeposition strategy. Benefiting from the large surface area and abundant pore structure of carbon-modified nitrogen-doped MXene nanosheets (NS), as well as the high conductivity of silver (Ag) NS, the electrolyte ion/electron transport paths are significantly improved. Furthermore, the distributed GO in the P(VDF-HFP) separator could form a high-speed continuous ion transport channel, thus enhancing the ionic conductivity. At a power density of 40-200 µW cm-2, the CFSC shows a high energy density of 0.7-3.39 µWh cm-2. The as-prepared CFSC also maintains an excellent capacitance retention rate of 90.3% even after 15â¯000 charge-discharge cycles. This work provides a general strategy for manufacturing high-performance, flexible, and wearable SCs.
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Despite the promising potential of elemental sulfur-based denitrification (ESDeN) packed-bed progresses, challenges such as excessive biofilm growth and gas entrapment persist, leading to denitrification deterioration. Water flush (WF) is recognized as an effective strategy, yet its effects remain underexplored. To address this knowledge gap, this study systematically investigated WF effects on ESDeN packed-bed denitrification. Results demonstrated that controlling WF effectively regulated denitrification, achieving superior and stable rates. Compared to no WF (0.45 kgN·m-3·d-1), rates improved by 1.20 â¼ 1.56 times under low-frequency (weekly WF, 0.54 kgN·m-3·d-1) and low-intensity WF (0.54 â¼ 0.70 kgN·m-3·d-1). High-frequency (hours WF) and high-intensity WF (30 & 50 m/h) further amplified denitrification rates by 1.73 â¼ 2.29 times. The enhanced denitrifications under low-frequency/intensity WF were mainly attributed to prolonged actual hydraulic retention time (AHRT), while high-frequency/intensity WF improved both AHRT prolonging and biofilm thinning, facilitating mass transfer. This study offers a promising avenue for fine-tuning denitrification rates via strategic WF adjustments.
Subject(s)
Biofilms , Denitrification , Sulfur , Water/chemistry , Bioreactors , Water Purification/methods , Waste Disposal, Fluid/methodsABSTRACT
This was a single-arm, multicenter, open-label phase I trial. Lentiviral vectors (LV) carrying the ABCD1 gene (LV-ABCD1) was directly injected into the brain of patients with childhood cerebral adrenoleukodystrophy (CCALD), and multi-site injection was performed. The injection dose increased from 200 to 1600 µL (vector titer: 1×109 TU/mL), and the average dose per kilogram body weight ranges from 8 to 63.6 µL/kg. The primary endpoint was safety, dose-exploration and immunogenicity and the secondary endpoint was initial evaluation of efficacy and the expression of ABCD1 protein. A total of 7 patients participated in this phase I study and were followed for 1 year. No injection-related serious adverse event or death occurred. Common adverse events associated with the injection were irritability (71%, 5/7) and fever (37.2 â-38.5 â, 57%, 4/7). Adverse events were mild and self-limited, or resolved within 3 d of symptomatic treatment. The maximal tolerable dose is 1600 µL. In 5 cases (83.3%, 5/6), no lentivirus associated antibodies were detected. The overall survival at 1-year was 100%. The ABCD1 protein expression was detected in neutrophils, monocytes and lymphocytes. This study suggests that the intracerebral injection of LV-ABCD1 for CCALD is safe and can achieve successful LV transduction in vivo; even the maximal dose did not increase the risk of adverse events. Furthermore, the direct LV-ABCD1 injection displayed low immunogenicity. In addition, the effectiveness of intracerebral LV-ABCD1 injection has been preliminarily demonstrated while further investigation is needed. This study has been registered in the Chinese Clinical Trial Registry (https://www.chictr.org.cn/, registration number: ChiCTR1900026649).
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Polycarboxylate superplasticizers BMC-L and BMC-S were utilized as modifiers in the formulation of novel cement-based grouting materials. Indoor tests were conducted on 32 groups of cement slurries, varying by water-cement ratio (0.5:1 and 0.6:1) and modifier content (0, 2‱, 4‱, 6‱, 8‱, 10‱, 12‱, and 14‱), to test their density, funnel viscosity, water separation rate, and stone rate. Four groups of slurry modified with BMC-L were selected as the preferred slurry, and the apparent viscosity test, uniaxial, and triaxial compression test of the slurry stone body were conducted. The study investigated the influence of BMC-L on various properties of the slurry, including its apparent viscosity, uniaxial compressive strength, stress-strain relationships, shear strength parameters, and elastic modulus. Ultimately, the pore structure and phase composition of the slurry stone body were detected by Nuclear Magnetic Resonance (NMR) and X-ray Diffraction (XRD), and the impact of BMC-L on slurry performance was examined from a microstructural perspective. Results indicate that the two polycarboxylate superplasticizers exert minimal influence on the density and water separation rate of the slurry. Within the effective incorporation range of the polycarboxylate superplasticizer, increasing the dosage correlates with a decrease in both the stone rate and viscosity of the slurry. BMC-L significantly enhances the mechanical properties of the slurry stone body by promoting more complete cement hydration and reducing porosity. The uniaxial compressive strength of slurry stone body with a 6 ‱ BMC-L dosage reached 29.7 MPa after 7 days and 38.5 MPa after 28 days of curing, representing increases of 118.4% and 64%, respectively, compared to masonry with 0 BMC-L dosage. The shear strength parameters and elastic modulus of the slurry stone body also showed corresponding increases.
ABSTRACT
BACKGROUND: Gastrointestinal tumor organoids serve as an effective model for simulating cancer in vitro and have been applied in basic biology and preclinical research. Despite over a decade of development and increasing research achievements in this field, a systematic and comprehensive analysis of the research hotspots and future trends is lacking. AIM: To address this problem by employing bibliometric tools to explore the publication years, countries/regions, institutions, journals, authors, keywords, and references in this field. METHODS: The literature was collected from Web of Science databases. CiteSpace-6.2R4, a widely used bibliometric analysis software package, was used for institutional analysis and reference burst analysis. VOSviewer 1.6.19 was used for journal co-citation analysis, author co-authorship and co-citation analysis. The 'online platform for bibliometric analysis (https://bibliometric.com/app)' was used to assess the total number of publications and the cooperation relationships between countries. Finally, we employed the bibliometric R software package (version R.4.3.1) in R-studio, for a comprehensive scientific analysis of the literature. RESULTS: Our analysis included a total of 1466 publications, revealing a significant yearly increase in articles on the study of gastrointestinal tumor organoids. The United States (n = 393) and Helmholtz Association (n = 93) have emerged as the leading countries and institutions, respectively, in this field, with Hans Clevers and Toshiro Sato being the most contributing authors. The most influential journal in this field is Gastroenterology. The most impactful reference is "Long term expansion of epithelial organs from human colon, adenoma, adenocarcinoma, and Barrett's epithelium". Keywords analysis and citation burst analysis indicate that precision medicine, disease modeling, drug development and screening, and regenerative medicine are the most cutting-edge directions. These focal points were further detailed based on the literature. CONCLUSION: This bibliometric study offers an objective and quantitative analysis of the research in this field, which can be considered as an important guide for next scientific research.