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Acute myeloid leukemia (AML) is an aggressive hematologic cancer in adults. Some patients exhibit restricted T cell infiltration and do not respond to routine treatments. This may be prevented by enhancing adaptive immunity by stimulating innate immune cells inside the tumor microenvironment (TME). To activate the adaptive immunological reaction against tumors, type I interferons (IFNs) can promote the presentation of tumor-specific cytotoxic T lymphocyte (CTL) cell recruitment. During the activation of innate immunity, cyclic di-nucleotides (CDNs) bind to and stimulate the stimulator of interferon genes (STING), a protein localized inside the endoplasmic reticulum (ER) membrane, resulting in the expression of type I IFNs. The efficacy of STING agonists as effective stimulators of the anti-tumor response in AML is being investigated in numerous clinical studies. Therefore, the purpose of this investigation was to thoroughly review existing knowledge in this field and provide perspective into the clinical potential of STING agonists in AML.

Background: This study aimed to establish predictive models based on features of Conventional Ultrasound (CUS) and elastography in a multi-center study to determine appropriate preoperative diagnosis of malignancy in thyroid nodules with different risk stratification based on 2017 Thyroid Imaging Reporting and Data System by the American College of Radiology (ACR TI-RADS) guidelines.Methods: Five hundred forty-eight thyroid nodules from three centers pathologically confirmed by the cytology or histology were retrospectively enrolled in the study, which were examined by CUS and elastography before fine needle aspiration (FNA) and surgery. Characteristics of CUS of thyroid nodules were reviewed according to 2017 ACR TI-RADS. Binary logistic regression analysis was used to develop the prediction models based on the different risk stratification of CUS features and elastography which were statistically significant. Values of predictive models were evaluated regarding the discrimination and calibration.Results: Binary logistic regression showed that patients’ age, taller-than-wider, lobulated or irregular boundary, extra-thyroid extension, microcalcification and the elastic parameter of Virtual touch tissue imaging quantification (VTIQ) max were independent predictors for thyroid malignancy (p0.05).Conclusions: Predictive models combined CUS and elastography features would aid clinicians to make appropriate preoperative diagnosis of thyroid nodules among different risk stratification. The elastography parameter of VTIQ max has the priority in distinguishing thyroid malignancy with moderately suspicious (ACR TR4).

With the recent increase in global focus on green energy, the application of thermal infrared remote sensing data for the detection of geothermal anomalies has attracted wide attention as it can overcome the difficulty of using only ground surveying. This study aimed to highlight areas of geothermal anomalies with land surface temperature (LST) time series data in winter derived from thermal infrared remote sensing. To extract LST anomaly areas in the Ruili Basin for geothermal prospecting, nine types of data on the study area in winter during 2014 ~ 2021 from Landsat 8 were analyzed. Landsat 8 LST inversion data based on the mono-window algorithm (MWA) can be used to identify hot springs, volcanoes, and other heat-related phenomena. Superimposing LST anomalies for each cycle through drilling data, excluding the heat island effect, geothermal anomaly regions could be plotted. The results show that the accuracy of MWA LST varied within 2 K, which is acceptable for geothermal energy and higher than those of the radiative transfer equation (RTE) algorithm and MODIS LST products. Three high-LST regions in the southeast of the study area were identified as geothermal anomaly areas (A, B, and C), and region B was further verified through a comprehensive field investigation of geothermal wells, supplemented by the temperature gradient (TG) method. The findings reveal that the distribution of geothermal anomaly areas and high-LST areas are highly consistent with the northeast trending fault structure; faults act as thermal channels and help in accurately detecting local LST anomalies. Overall, the infrared remote sensing method proved to be a valid technique for detecting LST anomalies. Considering the synergy between thermal infrared surface detection and subsurface exploration methods, the identification of known geothermal fields (B) and other possible areas (A and C) has significance in the upscaling of local geologic information to regional prospecting, thus providing a direction for future geothermal research.

Clearance of hepatitis B surface antigen (HBsAg) is an ideal therapeutic goal for patients with chronic hepatitis B virus (HBV) infection. Haematopoietic stem cell transplantation (HSCT) is the most effective therapy for a variety of haematological diseases. For patients with chronic HBV infection who received allo-HSCT, recipient hepatitis B serological status might change after allo-HSCT; however, data on the loss of HBsAg following allo-HSCT are relatively rare. We first reviewed patients with chronic HBV infection who received allo-HSCT in our centre from 2010 to 2020, and 125 patients were included in our study. A total of 62 patients (49.6%) with chronic HBV infection achieved HBsAg loss after allo-HSCT. Positivity for HBeAb and HBsAb in donors as well as no cytomegalovirus (CMV) infection were identified as independent risk factors for HBsAg loss after allo-HSCT. A predictive model including positivity for HBeAb and HBsAb in donors and no CMV infection was subsequently developed and performed well with effective discrimination and calibration. In addition, patients could benefit when this model is used in the clinic, as revealed via decision-curve analysis (DCA). However, multicentre prospective studies are required for validation.

Huangtai algal blooms are key indicators of eutrophication and lake-ecosystem damage. Understanding the spatiotemporal heterogeneity of their growth is critical for preserving the ecological environment. The dimidiate pixel model is commonly used to estimate vegetation coverage; however, indices such as the normalized difference vegetation index have not been specifically constructed for the Huangtai algae spectrum and thus are not specific or sufficiently precise for use as indicators. Therefore, we propose a new dimidiate pixel model based on a novel additive vegetation index to calculate the Huangtai algal coverage for each pixel using Landsat multispectral satellite images with 30-m resolution. The results showed that the additive vegetation index with R

Various targets need to be accomplished before the dream of sustainable development comes true. Among these targets, increasing renewable energy demand, reducing carbon intensity, and achieving green growth are the most noticeable. Therefore, the present study focuses on capturing digital financial inclusion's impact on renewable energy demand, carbon intensity, and green growth in the presence of ICT trade and environmental policy stringency in China. To empirically estimate the model, we have applied ARDL covering the time span from 1995 to 2020. The results state that the estimated coefficients attached to education, ATMS, and environmental policy stringency are positively significant in the renewable energy and green growth model and negatively significant in the carbon intensity model. From these results, we confer that education, digital financial inclusion, and environmental policy stringency are good for increasing renewable energy demand, reducing carbon intensity, and achieving green growth in China. In the short run, some of the estimates are negative; hence, we conclude that the results are inconclusive. The results recommend some imperative policy suggestions.

Urbanization has been a global phenomenon producing great environmental and ecological challenges including species composition shifts in urban areas. To evaluate the interaction networks of the inhabitant metacommunities in urban parks, we applied the nestedness analysis using ecological survey data of birds, reptiles, frogs, and butterflies among 16 parks in Taipei City of Taiwan and identified critical environmental factors for biodiversity conservation. Results found significant nestedness of the metacommunities among these parks, which indicated strong interaction networks and the importance of urban parks for sustaining these metacommunities. In addition, various types of land use had different effects on the species incidence of birds, reptiles, frogs, and butterflies. It demonstrates that landscape design should consider the taxonomic differences in the development of conservation guidelines. Results also showed that the area of parks and the area of woodlot in the park were critical elements for the nested structure. Nonetheless, abundant bird generalists were found to be highly related to the area of buildings within parks, distance to forests, rivers, and the neighbouring parks. Moreover, exotic species were found to affect the interaction networks of native species. However, based on the current information, we cannot confirm the actual effects of the exotic species on the native assemblages. Reptiles and frogs appeared to be more easily threatened by land development and habitat fragmentation due to their lower vagility. In this regard, we suggest that conservation action should focus on preserving green space with large areas and constructing green corridors, creating crucial elements, and increasing the vertical complexity in the parks for species with various vagilities. We believe these strategies can help reduce the impact of urbanization to retain healthy interactions and connections of metacommunities among habitats for effective biodiversity conservation in urban areas.

Background Acute kidney injury (AKI) is a severe complication of sepsis, and is strongly correlated with MicroRNAs (miRNAs). However, the mechanism of miR-22 on sepsis-induced AKI is not clearly understood. The study aimed to explore the role and mechanism of miR-22 on AKI. Methods The AKI models were established by cecal ligation and puncture (CLP) surgery in SD rats and lipopolysaccharide (LPS) induction in HBZY-1 cells. In AKI rats, the content of serum creatinine (SCr) and blood urea nitrogen (BUN) were detected. Kidney tissues were pathologically examined by H&E and PAS staining. The LPS-induced HBZY-1 cells were transfected with mimics miR-22, si-HMGB1, or oe-HMGB1. miR-22 and HMGB1 expression was detected in vivo and in vitro. In transfected cells, HMGB1/TLR4/NF-κB pathway-related protein expressions were measured by Western blot. The relationship between miR-22 and HMGB1 was assessed by a dual-luciferase gene report. Inflammatory cytokine levels in serum and cells were assessed by ELISA. Results In AKI rats, kidney injury was observed, accompanied by the down-regulated miR-122 expression and up-regulated HMBG1 expression. The dual-luciferase report found miR-22-3p could targetly regulate HMBG1. Furthermore, both in vitro and in vivo experiments revealed that the releases of inflammatory cytokine were increased after AKI modeling, but the situation was reversed by mimics miR-22 or si-HMGB1 in vitro. In HBZY-1 cells, mimics miR-22 could suppress LPS-induced overexpression of HMGB1/TLR4/NF-κB signaling pathway-related proteins. However, the oe-HMGB1 addition reversed the effect of mimics miR-22. Conclusion miR-22 can inhibit the inflammatory response, target the HMGB1, and inhibit the HMGB1/TLR4/NF-kB pathway, to attenuate the sepsis-induced AKI, which indicates that miR-22 may serve as a potential treatment target in sepsis-induced AKI.

The present study was conducted to evaluate the clinical, pathological response, and prognosis characteristics of human epidermal growth factor receptor 2 (HER2)-low breast cancer in the neoadjuvant chemotherapy setting.Patients with HER2-negative breast cancer who received neoadjuvant chemotherapy from January 2017 to December 2019 were retrospectively analyzed. HER2-negative breast cancer was divided into two groups: HER2-zero (defined as immunohistochemistry [IHC] 0) and HER2-low (defined as IHC 1+, or IHC 2+ and fluorescence in-situ hybridization-negative.Overall, 314 patients with HER2-negative breast cancer were analyzed. The proportion of HER2-low patients with hormone receptor (HR)-positive disease was higher than in triple-negative breast cancer (TNBC; 75.3% vs. 63.2%, p = 0.032). In HR-positive breast cancer, HER2-low tumors presented less nodal involvement (p = 0.023) and earlier clinical stage (p = 0.015) compared with HER2-zero tumors; however, in TNBC, HER2-low patients had a later clinical stage (p = 0.028). With the pathological complete response (pCR) defined as ypTis/0ypN0, there was no difference in pCR rates among the entire cohort, HR-positive disease, and TNBC. However, with the pCR defined as ypT0ypN0, the pCR rate in HER2-low breast cancer was significantly lower than HER2-zero breast cancer in the entire cohort (24.3% vs. 36.4%, p = 0.032) and the HR-positive subgroup (18.7% vs. 32.1%, p = 0.035), but not for TNBC. Multivariate analysis demonstrated that HER2 status (low vs. zero) was an independent predictive factor for pCR (p = 0.013) in HR-positive breast cancer. There were no statistically significant differences in 3-year disease-free survival and overall survival between HER2-low and HER2-zero breast cancer among the entire cohort, HR-positive disease, and TNBC.HER2-low breast cancer exhibits specific clinical features and different response to treatment associated with HR status in the neoadjuvant chemotherapy setting.

Previous diffusion tensor imaging (DTI) studies have mainly focused on dose-dependent white matter (WM) alterations 1 month to 1 year after radiation therapy (RT) with a tract-average method. However, WM alterations immediately after RT are subtle, resulting in early WM alterations that cannot be detected by tract-average methods. Therefore, we performed a study with an along-tract method in patients with brain metastases to explore the early dose-response pattern of WM alterations after RT.Sixteen patients with brain metastases underwent DTI before and 1-3 days after brain RT. DTI metrics, such as fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD), were calculated. Along-tract statistics were then used to resample WM fibre streamlines and generate a WM skeleton fibre tract. DTI metric alterations (post_RT-pre_RT DTI metrics) and the planned doses (max or mean doses) were mapped to 18 WM tracts. A linear fixed model was performed to analyse the main effect of dose on DTI metric alterations.AD alterations in the left hemispheric uncinated fasciculus (UNC_L) were associated with max doses, in which decreased AD alterations were associated with higher doses.Our findings may provide pathological insight into early dose-dependent WM alterations and may contribute to the development of max dose-constrained RT techniques to protect brain microstructure in the UNC_L.

Vancomycin is the drug of choice in the treatment of MRSA infections. In a published vancomycin population pharmacokinetic study on neonates in Singapore healthcare institutions, it was found that vancomycin clearance was predicted by weight, postmenstrual age, and serum creatinine. The aim of this study was to externally validate the vancomycin population pharmacokinetic model to develop a new dosage regimen in neonates, and to compare this regimen with the existing institutional and NeoFaxA retrospective chart review of neonates who received vancomycin therapy and therapeutic drug monitoring was conducted. The median prediction error percentage was calculated to assess bias, while the median absolute prediction error percentage and the root mean squared error percentage were calculated to assess precision. The new dosage regimen was developed using Monte Carlo simulation.A total of 20 neonates were included in the external validation dataset. Eighteen of them were premature, with a median gestational age of 27.7 (25.9-31.5) weeks and postmenstrual age of 30.5 (27.3-34.3) weeks at the point of vancomycin initiation. No apparent systematic bias was found in the predictions of the model. The external validation performed in the current study found the model to be generally unbiased. Our new vancomycin dosage regimen was able to achieve target trough concentrations and area under the curve (AUCThe pharmacokinetic model built in the previous study can be used to conduct reliable population simulations of our Asian neonatal population in Singapore. The new dosage regimen was able to achieve target trough concentrations and AUC

Monascus species are the producers of Monascus azaphilone pigments (MonAzPs) and lipid-lowering component Monacolin K, which have been widely used as food colorant and health products. In this study, silent information regulator 2 (Sir2) homolog (MrSir2) was characterized, and its impacts on the development and MonAzPs production of Monascus ruber were evaluated. Enzyme activity test in vitro showed that MrSir2 was an NAD

Objectives Dry weight assessment (DWA) is an important part of dialysis and fluid management in patients receiving renal replacement therapy. With the development of bioimpedance analysis (BIA), the development of the direct segmental multi-frequency BIA (DSM–BIA) has provided a more convenient measure for DWA of dialysis patients, but its accuracy remains unclear. This study was designed to evaluate the application of DSM–BIA in DWA of continuous ambulatory peritoneal dialysis (CAPD) patients. Design This is a cross-sectional study. Using the conventional BIA as a reference, we examined the accuracy of the DSM–BIA technique for assessing dry weight in CAPD patients and analyzed the potential factors influencing their fluid volume status. Setting and participants A total of 31 patients with end-stage renal disease receiving CAPD and 310 healthy volunteers were recruited for this study. Methods The intraclass correlation coefficients (ICC) and Bland–Altman plots were used to assess the consistency between DSM–BIA and the conventional BIA for DWA. Univariate and multivariate linear regression analyses were used to explore the influencing factors associated with the edema index. Results DSM–BIA and the conventional BIA technology were consistent in DWA in CAPD patients (ICC female 0.972, ICC male 0.882, ICC total 0.960). Similarly, Bland–Altman plots showed good agreements between the two methods in DWA for both genders. Univariate and multivariate linear regression analysis showed both eGFR level (P = 0.04) and serum NT-pro BNP concentration (P = 0.007) were positively correlated with the ratio of extracellular water to total body water (ECW/TCW). Conclusions DSM–BIA in DWA has good accuracy in clinical applications and has potential application value for fluid volume management in CAPD patients.