The L band frequency shows high sensitivity to sea surface salinity. More stable brightness temperature (TB) measurements are required for L-band radiometers to reduce salinity retrieval errors than ...for high-frequency radiometers. Due to the complexity of L-band synthetic aperture radiometers, a carefully selected cold-sky target should be viewed using an L-band synthetic aperture radiometer for the purpose of absolute TB calibration since the celestial sky is relatively well characterized and stable in the L band. A novel, effective cold-sky calibration strategy is presented in this paper. The strategy of cold-sky calibration of the synthetic aperture radiometer is applied when and where the antenna main lobe points to the ‘flat’ celestial sky, and the impact of each type of foreign source, such as the sun or moon, on visibility values should be minimized in the meantime. Additionally, antenna thermal stability is also considered, which can cause antenna deformation, and the antenna patterns are affected. A high-precision and high-fidelity simulator is built for the cold-sky calibration optimized strategy. The orbital beta angle is introduced to characterize the variation in space environment temperatures. A planet that is considered spherical in shape requires significantly less computation than an ellipsoid one in the simulator. The trade-off study results for the planet shape assumption in the cold-sky calibration simulator are presented. Finally, the calibration uncertainty and performance are assessed.
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are recommended for type 2 diabetes mellitus patients with impaired renal function, but the actual situation of SGLT2i using is unclear. Therefore, ...in this real-world study, we analyzed the treatment scheme and clinical characteristics of SGLT2i in patients with diabetic kidney disease (DKD). We included DKD patients hospitalized in the First Affiliated Hospital of Zhengzhou University from October 2017 to March 2020. The Apriori algorithm of association rules was used to analysis treatment scheme prescribing SGLT2i and other different combinations of hypoglycemic drugs. SGLT2i was used in 781 (12.3%) of 6336 DKD patients, both number and proportion of patients using SGLT2i increased from 2017 to 2020 (1.9% to 33%). Nighty-eight percent of all DKD patients using SGLT2i were combined with other glucose-lowering agents, and insulin, metformin and alpha-glucosidase inhibitors are most commonly used in combination with hypoglycemic drugs. Multivariate analysis showed that compared with non-SGLT2i group, patients using SGLT2i were associated with younger age, higher BMI, higher HbA1c, preserved kidney function, dyslipidemia and combined with ACEI/ARB and statins. In this real-world study, use of SGLT2i in DKD patients is still low. Most patients performed younger age and in the early stages of chronic kidney disease with poor glycemic control. Clinical inertia should be overcome to fully exert the cardiorenal protective effects of SGLT2 inhibitors, with attention to rational drug use.
Herein, a simple and feasible electrochemical immunosensing method for simultaneous voltammetric detection of two immunoglobulin proteins, human IgG (HIgG) and rabbit IgG (RIgG), was developed using ...two distinguishable signal-generation tags on the same electrode. The immunosensor was prepared by immobilizing two Fab antibody fragments on a gold electrode. After this, Cu and Cd nanocrystals, as nanotags, were synthesized and functionalized with identical detection antibodies. Transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FTIR) were employed to characterize the Cu and Cd nanocrystals. The covalently modified electrode with the Fab antibody fragments through the Au-thiolate bond (to dispel the non-specific adsorption) was investigated via scanning electron microscopy (SEM). After the sandwiched immunoreaction, the antibody-modified nanocrystals were captured on the immunosensor, which could be interrogated in pH 3.5 HCl using square-wave anodic stripping voltammetry. Experimental results also indicated that the multiplexed immunoassay enabled the simultaneous detection of HIgG and RIgG in a single run with the similar linear range from 0.01 to 10 ng mL
, and the limits of detection (LODs) towards two analytes could be as low as 3.4 pg mL
(at 3σ). Acceptable assay results on precision, reproducibility, specificity, and method accuracy were also acquired. Importantly, the newly designed strategy avoided cross-talk and enzymatic introduction as compared to conventional electrochemical immunoassays, thus exhibiting a promising potential in clinical applications.
African swine fever (ASF) is an acute, hemorrhagic and highly contagious infectious disease caused by African swine fever virus (ASFV), which infects domestic pigs or wild boars. It is characterized ...by short course of disease, high fever and hemorrhagic lesions, with mortality of up to 100% from acute infection. Up to now, the lack of commercial vaccines and effective drugs has seriously threatened the healthy economic development of the global pig industry. ASFV is a double-stranded DNA virus and genome varies between about 170-194 kb, which encodes 150-200 viral proteins, including 68 structural proteins and more than 100 non-structural proteins. In recent years, although the research on structure and function of ASFV-encoded proteins has been deepened, the structure and infection process of ASFV are still not clear. This review summarizes the main process of ASFV infection, replication and functions of related viral proteins to provide scientific basis and theoretical basis for ASFV research and vaccine development.
Position transition training for general practitioners in Zhejiang Province started in 2017 and has since been held once a year. By the beginning of 2022, four training sessions were completed. The ...purpose of this survey was to establish the current situation of trainees after their graduation and provide reference for the evaluation of the training effect.
Of the 738 trainees who completed the training, 253 were contacted and followed up. A self-designed questionnaire was used to conduct the survey through online filling in. The content included questions to elucidate the following information: whereabouts after the training, registration as a general practitioner, undertaken general practice teaching and scientific research work, current occupational environment, improvement of post competence after receiving position transition training, willingness to complete survey, willingness to participate in future training programs, etc. RESULTS: A number of 253 valid questionnaires were collected with a recovery rate of 100%. Notably, 93.68% of the participants successfully completed their training and obtained the Training Certificate of General Practitioners. Further, 83.4% were registered as general practitioners, 82.94% of which added on the basis of the original registered scope of practice. Currently, most of them work in primary health care institutions, primarily occupied with medical treatment, chronic disease management, COVID-19 prevention and control, health education, and prevention and health care. Of them, 27.01% were currently undertaking teaching work, and only 3.32% of them were conducting scientific research work related to general practice. The overall satisfaction of the trainees in the three theoretical training bases was above 90%, with no statistically significant difference among them (P > 0.05). Importantly, 84.11% of the followed-up personnel hoped to continue to participate in similar training in the future to improve their general practitioner core competences.
The position transition training in Zhejiang Province has achieved good results, but the details of training and the implementation of policies in individual regions need to be improved. Most of the graduates were willing to continue their education, especially in general practitioners with special interests.
Sexually transmitted infections (STIs) are a significant global public health challenge due to their high incidence rate and potential for severe consequences when early intervention is neglected. ...Research shows an upward trend in absolute cases and DALY numbers of STIs, with syphilis, chlamydia, trichomoniasis, and genital herpes exhibiting an increasing trend in age-standardized rate (ASR) from 2010 to 2019. Machine learning (ML) presents significant advantages in disease prediction, with several studies exploring its potential for STI prediction. The objective of this study is to build males-based and females-based STI risk prediction models based on the CatBoost algorithm using data from the National Health and Nutrition Examination Survey (NHANES) for training and validation, with sub-group analysis performed on each STI. The female sub-group also includes human papilloma virus (HPV) infection.
The study utilized data from the National Health and Nutrition Examination Survey (NHANES) program to build males-based and females-based STI risk prediction models using the CatBoost algorithm. Data was collected from 12,053 participants aged 18 to 59 years old, with general demographic characteristics and sexual behavior questionnaire responses included as features. The Adaptive Synthetic Sampling Approach (ADASYN) algorithm was used to address data imbalance, and 15 machine learning algorithms were evaluated before ultimately selecting the CatBoost algorithm. The SHAP method was employed to enhance interpretability by identifying feature importance in the model's STIs risk prediction.
The CatBoost classifier achieved AUC values of 0.9995, 0.9948, 0.9923, and 0.9996 and 0.9769 for predicting chlamydia, genital herpes, genital warts, gonorrhea, and overall STIs infections among males. The CatBoost classifier achieved AUC values of 0.9971, 0.972, 0.9765, 1, 0.9485 and 0.8819 for predicting chlamydia, genital herpes, genital warts, gonorrhea, HPV and overall STIs infections among females. The characteristics of having sex with new partner/year, times having sex without condom/year, and the number of female vaginal sex partners/lifetime have been identified as the top three significant predictors for the overall risk of male STIs. Similarly, ever having anal sex with a man, age and the number of male vaginal sex partners/lifetime have been identified as the top three significant predictors for the overall risk of female STIs.
This study demonstrated the effectiveness of the CatBoost classifier in predicting STI risks among both male and female populations. The SHAP algorithm revealed key predictors for each infection, highlighting consistent demographic characteristics and sexual behaviors across different STIs. These insights can guide targeted prevention strategies and interventions to alleviate the impact of STIs on public health.
ABSTRACTGray sufu is a traditional Chinese fermented soybean curd, and its flavor is significantly influenced by bacterial community. In this study, volatile flavor compounds (VFCs) were examined by ...headspace solid‐phase microextraction (HS-SPME) in conjunction with gas chromatography and mass spectrometry (GC‐MS). Additionally, bacterial community was analyzed using high-throughput sequencing. The results showed that, a total of 156 VFCs were tentatively identified, in which 8 esters, 6 S/N-containing compounds, 3 alcohols, 3 aldehydes, 1 ketone and 3 other compounds were recognized as the main characteristic VFCs. The abundant S/N-containing compounds are the most important flavor characteristics of gray sufu. A total of 4 phyla and 12 genera were revealed as dominant bacteria. Firmicutes and Proteobacteria were the most abundant phylum, whereas Bacillus, Tetragenococcus and Lactococcus were the prevailing genera. According to the KEGG pathway annotation, amino acid metabolism (26.98%) was the highest metabolic pathway. Among them, aromatic amino acids metabolism accounted for the highest proportion, up to 34.94%. Correlation analysis showed that Lactobacillus, Tetragenococcus, Bacillus, Pseudomonas and Halanaerobium were the top five positive flavor-producing bacteria. The results will be helpful for understanding the fermentation mechanism of gray sufu and improving flavor quality by developing microbial regulation strategies.
CD8
T cells play an important role in anti-tumor immunity. Better understanding of their regulation could advance cancer immunotherapies. Here we identify, via stepwise CRISPR-based screening, that ...CUL5 is a negative regulator of the core signaling pathways of CD8
T cells. Knocking out CUL5 in mouse CD8
T cells significantly improves their tumor growth inhibiting ability, with significant proteomic alterations that broadly enhance TCR and cytokine signaling and their effector functions. Chemical inhibition of neddylation required by CUL5 activation, also enhances CD8 effector activities with CUL5 validated as a major target. Mechanistically, CUL5, which is upregulated by TCR stimulation, interacts with the SOCS-box-containing protein PCMTD2 and inhibits TCR and IL2 signaling. Additionally, CTLA4 is markedly upregulated by CUL5 knockout, and its inactivation further enhances the anti-tumor effect of CUL5 KO. These results together reveal a negative regulatory mechanism for CD8
T cells and have strong translational implications in cancer immunotherapy.
Lung cancer is a common comorbidity of heart failure (HF). The early identification of the risk factors for lung cancer in patients with HF is crucial to early diagnosis and prognosis. Furthermore, ...oxidative stress and immune responses are the two critical biological processes shared by HF and lung cancer. Therefore, our study aimed to select the core genes in HF and then investigate the potential mechanisms underlying HF and lung cancer, including oxidative stress and immune responses through the selected genes.
Differentially expressed genes (DEGs) were analyzed for HF using datasets extracted from the Gene Expression Omnibus database. Functional enrichment analysis was subsequently performed. Next, weighted gene co-expression network analysis was performed to select the core gene modules. Support vector machine models, the random forest method, and the least absolute shrinkage and selection operator (LASSO) algorithm were applied to construct a multigene signature. The diagnostic values of the signature genes were measured using receiver operating characteristic curves. Functional analysis of the signature genes and immune landscape was performed using single-sample gene set enrichment analysis. Finally, the oxidative stress-related genes in these signature genes were identified and validated
in lung cancer cell lines.
The DEGs in the GSE57338 dataset were screened, and this dataset was then clustered into six modules using weighted gene co-expression network analysis; MEblue was significantly associated with HF (cor =
0.72, p < 0.001). Signature genes including extracellular matrix protein 2 (ECM2), methyltransferase-like 7B (METTL7B), meiosis-specific nuclear structural 1 (MNS1), and secreted frizzled-related protein 4 (SFRP4) were selected using support vector machine models, the LASSO algorithm, and the random forest method. The respective areas under the curve of the receiver operating characteristic curves of ECM2, METTL7B, MNS1, and SFRP4 were 0.939, 0.854, 0.941, and 0.926, respectively. Single-sample gene set enrichment analysis revealed significant differences in the immune landscape of the patients with HF and healthy subjects. Functional analysis also suggested that these signature genes may be involved in oxidative stress. In particular, METTL7B was highly expressed in lung cancer cell lines. Meanwhile, the correlation between METTL7B and oxidative stress was further verified using flow cytometry.
We identified that ECM2, METTL7B, MNS1, and SFRP4 exhibit remarkable diagnostic performance in patients with HF. Of note, METTL7B may be involved in the co-occurrence of HF and lung cancer by affecting the oxidative stress immune responses.
Current treatments for T cell malignancies encounter issues of disease relapse and off-target toxicity. Using T cell receptor (TCR)Vβ2 as a model, here we demonstrate the rapid generation of an ...off-the-shelf allogeneic chimeric antigen receptor (CAR)-T platform targeting the clone-specific TCR Vβ chain for malignant T cell killing while limiting normal cell destruction. Healthy donor T cells undergo CRISPR-induced TRAC, B2M and CIITA knockout to eliminate T cell-dependent graft-versus-host and host-versus-graft reactivity. Second generation 4-1BB/CD3zeta CAR containing high affinity humanized anti-Vβ scFv is expressed efficiently on donor T cells via both lentivirus and adeno-associated virus transduction with limited detectable pre-existing immunoreactivity. Our optimized CAR-T cells demonstrate specific and persistent killing of Vβ2+ Jurkat cells and Vβ2+ patient derived malignant T cells, in vitro and in vivo, without affecting normal T cells. In parallel, we generate humanized anti-Vβ2 antibody with enhanced antibody-dependent cellular cytotoxicity (ADCC) by Fc-engineering for NK cell ADCC therapy.
