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Summary: The paper is devoted to the prescribed finite time attitude control for quadrotors. A novel prescribed finite time function is introduced, which is independent of initial conditions and design parameters. And a switched prescribed finite time controller is firstly designed, such that the quadrotor can not only converge to the desired attitude in a prescribed time, but also guarantee the stability of the quadrotor after the settling time. Simultaneously, it effectively avoids chattering issues at the controller's switching points. Finally, the simulation comparisons are carried out between the proposed control strategy and infinite time, finite time, traditional prescribed finite time control schemes to demonstrate the superiority of the developed controller. [ABSTRACT FROM AUTHOR]

Nitrate pollution is a global environmental problem, and mean nitrate levels have risen by an estimated 36% in global waterways since 1990. Tracing nitrate sources is important for water quality management, and nitrate isotopes (δ15N-NO3− and δ18O-NO3−) are commonly used for this purpose because of the different isotopic compositions of different sources. However, the impact of nitrate sorption on matrix and desorption from matrix on N and O isotopic composition of nitrate in liquid phase has not been well clarified. To explore the mechanism for the changes in nitrate concentration and isotopes in liquid phase during sorption and desorption, this study took a shale sample (enriched in clay minerals and commonly exposed in the Earth), conducted a series of laboratory experiments for nitrate sorption and desorption, and studied the impact of sorption and desorption on nitrate N and O isotopic composition in liquid phase. The results showed that the shale sample exhibited a rapid sorption and desorption rate for nitrate in the surface water samples, with the nitrate concentration in the solution decreasing from 14.3 mg/L to 4.1 mg/L within 5 min. The sorption data fit the Langmuir model better than that of the Freundlich model. The maximum possible sorption (Qmax) for the shale sample was estimated to be 46 μg/g. Preliminary laboratory experiments showed that changes in δ15N-NO3− values were not obvious, and changes in δ18O-NO3− values in liquid phase were minor during sorption and desorption of the shale sample, suggesting that nitrogen isotopic fractionation can be neglected, and the sorption of nitrate by the shale sample has a very limited impact on the distribution of nitrate isotopes in liquid phase. However, the impact of nitrate desorption on the nitrate isotopes in liquid phase depends on the isotopic composition of exchangeable nitrate in the solid phase, which may be related to antecedent water–rock interactions. This study provides important information for elucidating the evolution mechanism of nitrate and its isotopic compositions following sorption-desorption, and is conducive to revealing the nitrogen cycle law in the environment. [ABSTRACT FROM AUTHOR]

Objectives: To preoperatively evaluate the human epidermal growth factor 2 (HER2) status in breast cancer using mammographic radiomics features and clinical characteristics on a multi-vendor and multi-center basis. Methods: This multi-center study included a cohort of 1512 Chinese female with invasive ductal carcinoma of no special type (IDC-NST) from two different hospitals and five devices (1332 from Institution A, used for training and testing the models, and 180 women from Institution B, as the external validation cohort). The Gradient Boosting Machine (GBM) was employed to establish radiomics and multiomics models. Model efficacy was evaluated by the area under the curve (AUC). Results: The number of HER2-positive patients in the training, testing, and external validation cohort were 245(26.3%), 105 (26.3.8%), and 51(28.3%), respectively, with no statistical differences among the three cohorts (p = 0.842, chi-square test). The radiomics model, based solely on the radiomics features, achieved an AUC of 0.814 (95% CI, 0.784–0.844) in the training cohort, 0.776 (95% CI, 0.727–0.825) in the testing cohort, and 0.702 (95% CI, 0.614–0.790) in the external validation cohort. The multiomics model, incorporated radiomics features with clinical characteristics, consistently outperformed the radiomics model with AUC values of 0.838 (95% CI, 0.810–0.866) in the training cohort, 0.788 (95% CI, 0.741–0.835) in the testing cohort, and 0.722 (95% CI, 0.637–0.811) in the external validation cohort. Conclusions: Our study demonstrates that a model based on radiomics features and clinical characteristics has the potential to accurately predict HER2 status of breast cancer patients across multiple devices and centers. Clinical relevance statement: By predicting the HER2 status of breast cancer reliably, the presented model built upon radiomics features and clinical characteristics on a multi-vendor and multi-center basis can help in bolstering the model's applicability and generalizability in real-world clinical scenarios. Key Points: • The mammographic presentation of breast cancer is closely associated with the status of human epidermal growth factor receptor 2 (HER2). • The radiomics model, based solely on radiomics features, exhibits sub-optimal performance in the external validation cohort. • By combining radiomics features and clinical characteristics, the multiomics model can improve the prediction ability in external data. [ABSTRACT FROM AUTHOR]

Background: In recent years,the lack of specific markers for the diagnosis of colorectal cancer has led to an upward trend in both morbidity and mortality from this condition. There is an urgent need to identify molecular biomarkers that contribute to early cancer detection. This study aimed to identify specific exosomal microRNAs that hold potential as diagnostic biomarkers for CRC. Methods: We screened for differentially expressed miRNAs using the CRC exosome dataset GSE39833. To validate the results in the public database, we collected serum from 168 CRC patients and 168 healthy volunteers. The expression levels of exosomal miR‐1470 in healthy volunteers and CRC patients were analyzed using qRT‐PCR. To evaluate the diagnostic potential of the selected miR‐1470 in distinguishing CRC patients from healthy controls, we analyzed its receiver operating characteristic curve. To explore the biological functions of miR‐1470 in CRC cell lines, we detected the miR‐1470's ability to regulate the growth and metastasis of CRC cells by CCK8, transwell and other assays after transfection of miR‐1470 in SW480, HCT‐116 cells. Results: Exosomal miR‐1470 exhibited significant up‐regulation in CRC patients compared to healthy volunteers. The ROC curve analysis revealed an area under the curve (AUC) of 0.74 (95% confidence interval: 0.6876–0.7920) for exosomal miR‐1470, indicating its potential as a diagnostic biomarker. Furthermore, the expression level of miR‐1470 in CRC patients showed correlations with age, metastasis, and HDL content. We overexpressed miR‐1470 in CRC cell lines. CCK8 proliferation assay showed that miR‐1470 promoted the proliferation ability of SW480 and HCT‐116 cells. Transwell assay showed that miR‐1470 promoted the migration and invasion ability of SW480 and HCT‐116 cells. Conclusion: This suggested that non‐invasive diagnosis of CRC is possible by detecting the level of miR‐1470 in exosomes, which has important implications for early detection and treatment of this disease. [ABSTRACT FROM AUTHOR]

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy that is highly aggressive with a poor prognosis. There is no standard treatment for BPDCN. Although conventional chemotherapies are usually sensitive in the initial therapy, relapse and drug resistance are inevitable within a short duration. Targeted therapies have enlightened new prospects for the treatment of BPDCN, especially for those in a frail state and intolerable to standard chemotherapies or hematopoietic stem cell transplantation. Here, we report an 82-year-old man diagnosed with cutaneous-limited BPDCN. Considering the old age and limited involvement of the tumor, we reduced the dosage of venetoclax. His skin lesions subsided significantly after 1 cycle of azacytidine (100 mg d1-7) combined with reduced doses of venetoclax (200 mg d1-14). The reduction in the dose of venetoclax avoided severe myelosuppression while achieving satisfactory outcomes. The patient received 2 cycles of therapy with no skin lesions re-occurred for 7 months before relapsing. [ABSTRACT FROM AUTHOR]

Objectives: Edema is a complication of gamma knife radiosurgery (GKS) in meningioma patients that leads to a variety of consequences. The aim of this study is to construct radiomics-based machine learning models to predict post-GKS edema development. Methods: In total, 445 meningioma patients who underwent GKS in our institution were enrolled and partitioned into training and internal validation datasets (8:2). A total of 150 cases from multicenter data were included as the external validation dataset. In each case, 1132 radiomics features were extracted from each pre-treatment MRI sequence (contrast-enhanced T1WI, T2WI, and ADC maps). Nine clinical features and eight semantic features were also generated. Nineteen random survival forest (RSF) and nineteen neural network (DeepSurv) models with different combinations of radiomics, clinical, and semantic features were developed with the training dataset, and evaluated with internal and external validation. A nomogram was derived from the model achieving the highest C-index in external validation. Results: All the models were successfully validated on both validation datasets. The RSF model incorporating clinical, semantic, and ADC radiomics features achieved the best performance with a C-index of 0.861 (95% CI: 0.748–0.975) in internal validation, and 0.780 (95% CI: 0.673–0.887) in external validation. It stratifies high-risk and low-risk cases effectively. The nomogram based on the predicted risks provided personalized prediction with a C-index of 0.962 (95%CI: 0.951–0.973) and satisfactory calibration. Conclusion: This RSF model with a nomogram could represent a non-invasive and cost-effective tool to predict post-GKS edema risk, thus facilitating personalized decision-making in meningioma treatment. Clinical relevance statement: The RSF model with a nomogram built in this study represents a handy, non-invasive, and cost-effective tool for meningioma patients to assist in better counselling on the risks, appropriate individual treatment decisions, and customized follow-up plans. Key Points: • Machine learning models were built to predict post-GKS edema in meningioma. The random survival forest model with clinical, semantic, and ADC radiomics features achieved excellent performance. • The nomogram based on the predicted risks provides personalized prediction with a C-index of 0.962 (95%CI: 0.951–0.973) and satisfactory calibration and shows the potential to assist in better counselling, appropriate treatment decisions, and customized follow-up plans. • Given the excellent performance and convenient acquisition of the conventional sequence, we envision that this non-invasive and cost-effective tool will facilitate personalized medicine in meningioma treatment. [ABSTRACT FROM AUTHOR]

Background: Immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disease characterized by increased platelet destruction and impaired thrombopoiesis. The changes in platelet indices depend on the morphology and volume of platelets. Serum lipids have been found to affect platelet formation and activity in certain diseases, thus inducing the corresponding variation of platelet indices. Methods: Mendelian randomization (MR) analysis was performed based on databases. The clinical data from 457 ITP patients were retrospectively collected and analyzed, including platelet indices, serum lipids, hemorrhages and therapeutic responses. Results: MR analysis showed low high-density-lipoprotein-cholesterol (HDL-C), low apolipoprotein A-1, high triglyceride (TG) and high apolipoprotein B (ApoB) caused high platelet distribution width (PDW); high low-density-lipoprotein-cholesterol (LDL-C) increased mean platelet volume (MPV). In ITP, there were positive correlations between platelet count with TG, PDW with HDL-C and ApoB, and plateletcrit with TG and non-esterified fatty acid, and the correlation had gender differences. Bleeding scores were negatively correlated with cholesterol and LDL-C. LDL-C and homocysteine were risk factors for therapeutic responses. Conclusions: Serum lipids, especially cholesterol were tightly correlated with platelet indices, hemorrhage and therapeutic effects in ITP patients. These results provide clinical references for the management of serum lipids, and highlight the necessity to further explore the relationship between lipids and pathogenesis of ITP. Trial registration: No: NCT05095896, October 14, 2021, retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: Immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disease characterized by low platelet count and bleeding manifestations. However, some patients also suffered from atherosclerosis or even infarction. Apart from activated platelets, lipid metabolism takes a large part in the formation of atherosclerosis and metabolic syndrome. The lipid metabolic state in ITP patients is still unknown. Methods: We retrospectively reviewed 302 hospitalized ITP patients in our cohort, comparing their blood lipids, bleeding symptoms, metabolic diseases and treatment responses. Results: We found a high proportion of ITP patients suffered from hyperlipidemia, and other metabolic diseases including cardiovascular or cerebral atherosclerosis or infarction, hypertension, and type 2 diabetes. Hyperlipidemia was associated with severe bleeding and treatment refractoriness in ITP. Statins could alleviate thrombocytopenia and bleeding severity, and facilitate ITP treatment, while improving hyperlipidemia in ITP patients. Conclusions: Our present study demonstrated that lipid metabolism might play an indispensable role in ITP pathogenesis and development. [ABSTRACT FROM AUTHOR]

Demands are increasing for ultrashort pulse laser in industrial applications, where the gain bandwidth of most optical fiber material is not wide enough, and developing a wide bandwidth gain medium is challenging. Glass–ceramic fibers containing Nd3+/Yb3+ co‐doped YCa4O(BO3)3 nanocrystals were fabricated by the molten core method and successive heat treatment. After a careful heat treatment, Nd3+/Yb3+ co‐doped YCa4O(BO3)3 nanocrystals were precipitated in the fiber core. Enhanced broadband near‐infrared (NIR) emission from 850 to 1150 nm (bandwidth: ∼252 nm) was obtained in the glass–ceramic fiber compared to that of precursor fiber. These results suggest that the Nd3+/Yb3+ glass–ceramic fibers are promising for broadband NIR optical amplifications and lasers. [ABSTRACT FROM AUTHOR]

This paper studies the tracking control problem for a climate chamber control system used for determining volatile organic compounds. A new nonlinear controller, for the first time, is designed for the temperature and humidity control of a 30m3$30\text{ m}^3$ climate chamber. For one thing, based on the backstepping technology, an improved control method is proposed with the help of the implicit function theorem instead of employing system linearization. In this way, simplification of the controlled system can be avoidable so that the control accuracy is promoted. For another, without approximations by fuzzy logics or neural networks, the number of complex computations are reduced a lot so that the control rate is improved considerably. In the end, simulation is conducted by Matlab to validate the effectiveness and superiority of the proposed control method. [ABSTRACT FROM AUTHOR]

A single biomaterial is disadvantageous for constructing skin in vitro, so a mixed biomaterial is more conducive to skin research. In this study, agarose–chitosan scaffolds with a final concentration of 4% were constructed by freeze‐drying, in which the concentration ratios of agarose to chitosan were 1:3, 2:2, and 3:1. The scaffolds were coated with a 3 mg/ml collagen solution, and the mechanical properties were evaluated by studying density, porosity, swelling rate, and degradation rate. The results demonstrated that the agarose–chitosan scaffolds were porous, with porosity reaching 93%. Their densities ranged from 0.1 to 0.16 g/cm3. Analysis of Young's modulus showed that the mechanical properties of the agarose–chitosan scaffolds were significantly enhanced when the agarose content in the agarose–chitosan scaffolds was increased. Moreover, the density and Young's modulus of the agarose–chitosan scaffolds of different concentration ratios were significantly different (p < 0.01). These scaffolds can withstand a certain amount of external pressure, such as that of human skin, making them more suitable for further skin replacement research. In addition, the results of thiazolyl blue tetrazolium bromide (MTT) cell assay and immunofluorescence staining showed that the collagen‐coated agarose–chitosan scaffolds were conducive to keratinocyte proliferation and differentiation. The MTT results revealed significant differences between the agarose–chitosan scaffolds coated with collagen and the agarose–chitosan scaffolds without collagen (p < 0.05). This study provides the potential for in vitro skin research and applications. [ABSTRACT FROM AUTHOR]

Summary: Immune thrombocytopenia (ITP) is an autoimmune haemorrhagic disease, in which the overactivation of T cells is crucial in the pathogenesis. Atorvastatin (AT), a lipid‐lowering medicine, has shown promising immunomodulatory effects in certain inflammatory conditions. However, the immunoregulatory role of AT in ITP remains elusive. To investigate the effect of AT in the treatment of ITP, cluster of differentiation 4 (CD4)+ T cells were isolated from patients with ITP and cultured with different dosages of AT. We found that AT significantly inhibited cell proliferation, led to cell cycle arrest, induced apoptosis, and repressed the activation of CD4+ T cells in vitro. ITP murine models were then established, and results showed that AT treatment led to faster recovery of the platelet count to normal and exhibited comparable immunomodulatory function. Furthermore, we found the phosphorylation of mammalian target of rapamycin (mTOR), protein kinase B (AKT) and extracellular signal‐regulated kinase (ERK), as well as activation of rat sarcoma virus (RAS) were all reduced dramatically after AT treatment in vitro. In conclusion, our present study demonstrated that AT could reinstate the functions of CD4+ T cells by inhibiting the excessive activation, proliferation, and survival of CD4+ T cells in ITP via the RAS/mitogen‐activated protein kinase kinase (MEK)/ERK and the mTOR/phosphatidylinositol‐3 kinase (PI3K)/AKT pathway. Therefore, we propose that AT could be used as a potential therapeutic option for ITP by restoring the over‐activated cellular immunity. [ABSTRACT FROM AUTHOR]

Yellow lasers are of great interest in biology, medicine and display technology. However, nonlinear emission of near-infrared lasers at yellow still presents particularly complex optical alignment to date. Here, to the best of our knowledge, we demonstrate the fabrication of a NaLa(WO4)2: Dy3+ glass-ceramic fiber (GCF) for the first time. More importantly, the emission band of the GCF, which is around 575 nm, has a wide full-width half maximum (FWHM) of 18~22 nm, which is remarkably larger than that of the Dy3+-doped YAG crystal (<7 nm). The precursor fiber (PF) was drawn using the molten core drawing (MCD) method. In particular, benefiting from the in situ nanocrystals fabricated in the amorphous fiber core after thermal treatment, the resultant glass-ceramic fiber exhibits a five-times enhancement of luminescence intensity around 575 nm, compared with the precursor fiber, while retaining its broadband emission. Overall, this work is anticipated to offer a high potential GCF with prominent bandwidth for the direct access of a tunable yellow laser. [ABSTRACT FROM AUTHOR]

The critical need to enhance the quality of indoor air leads to the improvement of catalyst activity for the removal of formaldehyde. Sepiolite can be utilized in catalytic reactions for its unique structure, composition and high surface area. The adhesion between sepiolite fibers and the blocked microporous channel (by impurities) demands the activation of natural sepiolite through acid treatment. This treatment successfully produces acid-modified sepiolite Pt-supported samples. The impacts of different acid concentrations, Pt loading content and calcination temperature on catalytic activity for formaldehyde (HCHO) oxidation are studied. The catalytic activity of HCHO is characterized and evaluated by techniques including specific surface area, X-ray diffraction, Fourier transform infrared spectrum, X-ray photoelectron spectroscopy and transmission electron microscopy. The results show the maximum specific area of sepiolite at the optimized 0.06 M acid concentration. Among all the prepared samples, the 0.02Pt/Sep catalyst calcined at 500 °C exhibits the highest catalytic activity for the oxidation of HCHO. [ABSTRACT FROM AUTHOR]

Treatment of oral squamous cell carcinoma remains a challenge due to a high incidence of treatment resistance, which is followed by tumor recrudescence and metastasis to the lymph nodes. Thus, it is important to explore novel inhibitors of OSCC. Here, we aimed to identify drugs that may cooperate with histone deacetylase inhibitors to reverse the EMT, inhibit EMT and cell migration and invasion, and contribute to therapeutic efficacy. We found that treatment with 4sc‐202 potently reversed the EMT and thereby inhibited cell migration and invasion in vitro, in part by inducing expression of the FoxO1 tumor‐suppressor gene. Furthermore, 4sc‐202 also synergized with Ink‐128 to inhibit tumor migration and invasion in vitro. Mechanistically, 4sc‐202 induced FoxO1 expression, whereas Ink‐128 promoted nuclear translocation of FoxO1. Our findings indicated that FoxO1 might reverse the EMT by interacting with Twist1 in OSCC. In conclusion, we identified an effective combination therapy involving class I histone deacetylase and mammalian target of rapamycin complex 1/2 inhibition that effectively blocked the EMT of tumor cells by upregulating FoxO1 expression to inhibit Twist1 transcription. These data have implications for developing new targets for early diagnosis and treatment of OSCC. [ABSTRACT FROM AUTHOR]

With the development of peripheral nerve tissue engineering, study of biodegradable materials have extensive applied prospect. Chitosan (Cs) is a promising candidate for neural tissue engineering due to its similar chemical structure to glycosaminoglycan. However, due to its lack of elasticity and flexibility, Cs often needs to be used in combination with other materials. In this study, three composite scaffolds were prepared by freeze-drying method: Cs/hyaluronic acid (HA)/gelatin (Gel), Cs/collagen (Col), and Cs/polyethylene glycol (PEG). Mechanical properties, swelling behavior, porosity, and conductivity of these materials have been characterized. Compared with pure Cs, the addition of other materials reduced the average pore size, while improved the mechanical properties of the composite scaffold. Furthermore, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), live/dead staining, cell morphology, and immunofluorescence staining were performed to evaluate the cytotoxicity, biocompatibility, and differentiation of rat pheochromocytoma (PC12) cells on Cs/HA/Gel, Cs/Col, and Cs/PEG composite scaffolds. Our results indicated that all these Cs-based composite scaffolds had good biocompatibility without cytotoxicity, while Cs/PEG scaffolds possessed higher cell survival rate and could promote the adhesion, proliferation, and differentiation of PC12 cells. The Cs-based composite scaffolds developed in this study can serve as promising substitutes for neural tissue regeneration. [ABSTRACT FROM AUTHOR]

Purpose: To explore the imaging changes of the liver and kidneys in COVID-19 survivors using variable flip angle (VFA) T1 mapping and intravoxel incoherent motion-diffusion weighted imaging (IVIM-DWI). Methods: This prospective study included 37 discharged COVID-19 participants and 24 age-matched non-COVID-19 volunteers who underwent abdominal MRI with VFA T1 mapping and IVIM-DWI sequencing as a COVID-19 group and control group, respectively. Among those discharged COVID-19 participants, 23 patients underwent two follow-up MRI scans, and were enrolled as the 3-month follow-up group and 1-year follow-up group, respectively. The demographics, clinical characteristics, and laboratory tests were collected. Imaging parameters of the liver and kidneys were measured. All collected values were compared among different groups. Results: The 3-month follow-up group had the lowest hepatic T1 value, which was significantly lower than the value in the control group (P < 0.001). Additionally, the 3-month follow-up group had the highest hepatic ADC and D values, cortical ADC and f values, which were significantly higher than those in the control group (for all, P < 0.05). The hepatic D value in the 1-year follow-up group decreased significantly in comparison with that in the 3-month follow-up group (P = 0.001). Compared to non-severe patients, severe cases had significantly higher hepatic D* and f*D* values (P = 0.031, P = 0.015, respectively). Conclusion: The dynamic alterations of hepatic and renal imaging parameters detected with T1 mapping and IVIM-DWI suggested that COVID-19 survivors might develop mild, non-symptomatic liver and kidney impairments, of which liver impairment could probably relieve over time and kidney impairment might be long-existing. [ABSTRACT FROM AUTHOR]

Compared with conventional white light emitting diodes, white lasers are highly desired for application in visible light communication due to their higher modulation bandwidth and light output power. However, the generation of white lasers in a single monolithic material constitutes a significant challenge due to its exacting requirements in the sophisticated design for simultaneous red, green, and blue oscillation. Herein, through a facile strategy, the design and preparation of a single monolithic material (the Pr3+ single-doped transparent glass ceramic (GC)) for emission color manipulation and white light generation are reported. By controlling the growth of 5–30 nm KYF4 nanocrystals in the glass matrix, the local field environment of Pr3+ evolves from an amorphous glass matrix to KYF4 nanocrystals, resulting in the emission color tuning from red via warm white to cold white. Impressively, the GC heat-treated at 520 °C for 2 h exhibits enhanced blue emission intensity which is approximately two orders of magnitude larger than that of glass. The feasibility of the target crystal growth in the glass matrix is validated via molecular dynamics simulations. In addition, a GC fiber with bright white light emission is successfully constructed. This work of tunable multicolor emission and white light generation from the Pr3+ single-doped GC opens up a new avenue for the development of modulated white light GC fiber lasers for application in future visible light communication. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to identify specific and sensitive exosomal miRNAs in diagnosing patients with colorectal cancer (CRC). Methods: Serum exosomes were isolated from 175 CRC patients and 172 healthy donors by ultracentrifugation and identified by transmission electron microscopy, nanoparticle tracking analysis and western blotting. Exosomal miRNA expression was detected by quantitative PCR and the results analyzed by receiver operating characteristic analysis to illuminate the diagnostic accuracy. Results: Both exosomal miR-377-3p and miR-381-3p were downregulated in CRC patients as well as in early-stage patients compared with healthy donors; they could serve as circulating biomarkers of diagnosis, including early diagnosis, for CRC, possessing favorable diagnostic efficiency. Conclusion: Exosomal miR-377-3p and miR-381-3p levels were downregulated in CRC patients and may be useful as novel and specific biomarkers for the diagnosis of CRC, especially early-stage CRC. [ABSTRACT FROM AUTHOR]

Background: To identify effective factors and establish a model to distinguish COVID-19 patients from suspected cases. Methods: The clinical characteristics, laboratory results and initial chest CT findings of suspected COVID-19 patients in 3 institutions were retrospectively reviewed. Univariate and multivariate logistic regression were performed to identify significant features. A nomogram was constructed, with calibration validated internally and externally. Results: 239 patients from 2 institutions were enrolled in the primary cohort including 157 COVID-19 and 82 non-COVID-19 patients. 11 features were selected by LASSO selection, and 8 features were found significant using multivariate logistic regression analysis. We found that the COVID-19 group are more likely to have fever (OR 4.22), contact history (OR 284.73), lower WBC count (OR 0.63), left lower lobe involvement (OR 9.42), multifocal lesions (OR 8.98), pleural thickening (OR 5.59), peripheral distribution (OR 0.09), and less mediastinal lymphadenopathy (OR 0.037). The nomogram developed accordingly for clinical practice showed satisfactory internal and external validation. Conclusions: In conclusion, fever, contact history, decreased WBC count, left lower lobe involvement, pleural thickening, multifocal lesions, peripheral distribution, and absence of mediastinal lymphadenopathy are able to distinguish COVID-19 patients from other suspected patients. The corresponding nomogram is a useful tool in clinical practice. [ABSTRACT FROM AUTHOR]

In patients with CH, 16.7% AA cases and 23.6% hMDS cases had two or more mutations while only one ITP patient had more than one mutation (Fig. The polyline represents the cumulative prevalence of CH in ITP patients, the bars show the percentage of patients with CH in different age groups. 1L), CH was positively correlated with bleeding severity as ITP patients with CH were 6.95 times more likely to develop severe bleeding than those without CH ( I P i = 0.008, Fig. N The initial response rate in patients with CH was lower compared with patients without CH though it did not reach statistical significance. [Extracted from the article]

Quantum dots (QD), mixed with carbon materials, have gained increasing interest in the last few years as electrocatalysts due to their outstanding properties, such as excellent catalytic activity and good thermodynamic stabilities. However, most QD‐carbon hybrids show lower catalytic activities than that theoretically predicted due to the aggregation of the QD‐carbon nanostructures during processing. Herein, biomass is used as a carbon source to prepare QD carbon nanostructures (Ni@CN) to address the aforementioned issue. The cells walls and membranes in the biomass materials are usually rich in sites that could regulate the deposition and growth of Ni from a salt precursor by a simple solution impregnation method. Due to the abundance of the seeding sits and the limited supply of Ni+, the Ni particles size is restricted to the QD level with 3–4 nm. The formed Ni compounds QD are strongly linked to the cells walls and membranes, which could be maintained after subsequent heat treatment. The prepared 3D architecture has high catalytic activity, large surface area, strong physical integration, and rapid charge transfer capability, which collectively enhances the performance toward oxygen evolution reaction and hydrogen evolution reaction, opening the door to empower the next‐generation green fuel conversion for carbon neutral. [ABSTRACT FROM AUTHOR]

This article studies the adaptive tracking control problem for stochastic nonlinear systems with unknown virtual control coefficients (UVCCs) being functions of system states. Without using the Nussbaum gain technique (NGT), a new method is introduced to deal with UVCCs. The novel adaptive laws are constructed to compensate parameter uncertainties and UVCCs. Using backstepping method, an adaptive controller is designed, which can ensure that the boundedness in probability of all the signals in the closed‐loop system. In the end, a numerical simulation example and a practical example are given to validate the effectiveness and superiority of the proposed controller. [ABSTRACT FROM AUTHOR]

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Fungal infections, especially candidiasis and aspergillosis, claim a high fatality rate. Fungal cell growth and function requires ATP, which is synthesized mainly through oxidative phosphorylation, with the key enzyme being F1Fo-ATP synthase. Here, we show that deletion of the Candida albicans gene encoding the δ subunit of the F1Fo-ATP synthase (ATP16) abrogates lethal infection in a mouse model of systemic candidiasis. The deletion does not substantially affect in vitro fungal growth or intracellular ATP concentrations, because the decrease in oxidative phosphorylation-derived ATP synthesis is compensated by enhanced glycolysis. However, the ATP16-deleted mutant displays decreased phosphofructokinase activity, leading to low fructose 1,6-bisphosphate levels, reduced activity of Ras1-dependent and -independent cAMP-PKA pathways, downregulation of virulence factors, and reduced pathogenicity. A structure-based virtual screening of small molecules leads to identification of a compound potentially targeting the δ subunit of fungal F1Fo-ATP synthases. The compound induces in vitro phenotypes similar to those observed in the ATP16-deleted mutant, and protects mice from succumbing to invasive candidiasis. Our findings indicate that F1Fo-ATP synthase δ subunit is required for C. albicans lethal infection and represents a potential therapeutic target. F1Fo-ATP synthase is a key enzyme for energy production in fungi. Here, the authors show that the δ subunit of the enzyme is required for Candida albicans lethal infection and represents a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Summary: Exosomes are released into extracellular fluids and have emerged as vital biological mediators in autoimmune diseases. Plasma‐derived exosomes have been reported to take part in the pathogenesis of primary immune thrombocytopenia (ITP), but the protein and miRNA cargoes have not been entirely elucidated. Via proteomic analysis and RNA sequencing on plasma‐derived exosomes from ITP patients and healthy controls, we found one upregulated exosomal protein (apolipoprotein E, ApoE), six downregulated exosomal miRNAs (miR‐584‐5p, miR‐4433a‐5p, miR‐4433b‐3p, miR‐6842‐3p, miR‐130b‐5p and miR‐222‐3p), and 10 upregulated exosomal miRNAs (miR‐29a‐3p, miR‐142‐5p, miR‐16‐2‐3p, miR‐29b‐3p, miR‐501‐3p, miR‐144‐5p, miR‐192‐5p, miR‐182‐5p, miR‐363‐3p and miR‐96‐5p) in ITP patients. The elevated exosomal protein candidate ApoE in the ITP cohort was further validated using western blot. Via quantitative real‐time polymerase chain reaction assays, three differentially expressed miRNAs (miR‐584‐5p, miR‐142‐5p and miR‐29b‐3p) were identified. This study provides direct evidence for a restricted signature of exosomal protein and miRNAs which distinguishes ITP from healthy controls. The results require further validation in larger independent ITP cohorts, which will provide insights into the potential pathophysiological significance of circulating exosomes in ITP. [ABSTRACT FROM AUTHOR]

Invasive fungal infections are a major cause of human mortality due in part to a very limited antifungal drug arsenal. The identification of fungal-specific pathogenic mechanisms is considered a crucial step to current antifungal drug development and represents a significant goal to increase the efficacy and reduce host toxicity. Although the overall architecture of F1FO-ATP synthase is largely conserved in both fungi and mammals, the subunit i/j (Su i/j, Atp18) and subunit k (Su k, Atp19) are proteins not found in mammals and specific to fungi. Here, the role of Su i/j and Su k in Candida albicans was characterized by an in vivo assessment of the virulence and in vitro growth and mitochondrial function. Strikingly, the atp18 Δ/Δ mutant showed significantly reduced pathogenicity in systemic murine model. However, this substantial defect in infectivity exists without associated defects in mitochondrial oxidative phosphorylation or proliferation in vitro. Analysis of virulence-related traits reveals normal in both mutants, but shows cell wall defects in composition and architecture in the case of atp18 Δ/Δ. We also find that the atp18 Δ/Δ mutant is more susceptible to attack by macrophages than wild type, which may correlate well with the abnormal cell wall function and increased sensitivity to oxidative stress. In contrast, no significant changes were observed in any of these studies for the atp19 Δ/Δ. These results demonstrate that the fungal-specific Su i/j, but not Su k of F1FO-ATP synthase may play a critical role in C. albicans infectivity and represent another opportunity for new therapeutic target investigation. Lay Abstract This study aims to investigate biological functions of fungal-specific subunit i/j and subunit k of ATP synthase in C. albicans oxidative phosphorylation and virulence potential. Our results revealed that subunit i/j, and not subunit k, is critical for C. albicans pathogenicity. [ABSTRACT FROM AUTHOR]

Summary: This retrospective study aimed to evaluate the relationship between plasma autoantibody species and rhTPO response in adult ITP patients who failed the first‐line treatments. Plasma anti‐glycoprotein (GP) IIb/IIIa and anti‐GPIb/IX autoantibodies were detected in 47·2% and 40·6% of the 123 patients, respectively. Overall response rate to rhTPO treatment in patients without anti‐GPIb/IX autoantibodies was significantly higher than patients with anti‐GPIb/IX autoantibodies (82·2% vs. 60·0%, P = 0·006). By contrast, no statistical difference in response rate was observed between patients with or without anti‐GPIIb/IIIa autoantibodies (74·1% vs. 72·3%, P = 0·819). Therefore, the presence of anti‐GPIb/IX autoantibodies might serve as a predictive factor for poor response to rhTPO treatment in ITP. [ABSTRACT FROM AUTHOR]

Background: KDM6A, a histone demethylase, is frequently mutated in bladder cancer (BCa). However, the role and detailed molecular mechanism of KDM6A involved in bladder cancer progression remains unknown. Methods: Tissue specimens were used to determine the expression levels and prognostic values of KDM6A and ARHGDIB. The MTT, colony formation, wound healing and Transwell migration and invasion assays were employed to detect the BCa cell proliferation, migration and invasion, respectively. Chemotaxis of macrophages was used to evaluate the ability of KDM6A to recruit macrophages. A subcutaneous tumour model and tail vein tumour injection in nude mice were used to assess the role of KDM6A in vivo. RNA sequencing, qPCR, Western blot, ChIP and phalloidin staining assay were performed to investigate the molecular functions of KDM6A. Dual-luciferase reporter assay was used to determine the effects of KDM6A and FOXA1 on the promoters of the ARHGDIB and KDM6A. Results: We showed that the KDM6A inhibited the motility and invasiveness of the BCa cells. Mechanistically, KDM6A promotes the transcription of ARHGDIB by demethylating histone H3 lysine di/trimethylation (H3K27me2/3) and consequently leads to inhibition of Rac1. EZH2, which catalyses the methylation of H3K27, functions to silence ARHGDIB expression, and an EZH2 inhibitor can neutralize the metastatic effect caused by KDM6A deficiency. Furthermore, we demonstrated that FOXA1 directly binds to the KDM6A promoter and thus transactivates KDM6A, leading to diminished metastatic potential. Conclusion: Our findings establish the critical role of the FOXA1-KDM6A-ARHGDIB axis in restraining the malignancy of BCa and identify KDM6A and EZH2 as potential therapeutic targets in the management of BCa. [ABSTRACT FROM AUTHOR]

Macrophages provide the first-line defense against invasive fungal infections and, therefore, escape from macrophage becomes the basis for the establishment of Candida albicans invasive infection. Here, we found that deletion of ATP2 (atp2 Δ/Δ) in C. albicans resulted in a dramatic decrease from 69.2% (WT) to 1.2% in the escape rate in vitro. The effect of ATP2 on macrophage clearance stands out among the genes currently known to affect clearance. In the normal mice, the atp2 Δ/Δ cells were undetectable in major organs 72 h after systemic infection, while WT cells persisted in vivo. However, in the macrophage-depleted mice, atp2 Δ/Δ could persist for 72 h at an amount comparable to that at 24 h. Regarding the mechanism, WT cells sustained growth and switched to hyphal form, which was more conducive to escape from macrophages, in media that mimic the glucose-deficient environment in macrophages. In contrast, atp2 Δ/Δ cells can remained viable but were unable to complete morphogenesis in these media, resulting in them being trapped within macrophages in the yeast form. Meanwhile, atp2 Δ/Δ cells were killed by oxidative stress in alternative carbon sources by 2- to 3-fold more than WT cells. Taken together, ATP2 deletion prevents C. albicans from escaping macrophage clearance, and therefore ATP2 has a functional basis as a drug target that interferes with macrophage clearance. [ABSTRACT FROM AUTHOR]

Cytotoxic T lymphocytes (CTLs)-mediated platelet destruction plays an important role in the pathogenesis of primary immune thrombocytopenia (ITP). The programmed cell death protein 1 (PD-1) signaling can turn off autoreactive T cells and induce peripheral tolerance. Herein, we found that the expression of PD-1 and its ligand PD-L1 on CD8+ T cells from ITP patients was decreased. Activating PD-1 pathway by PD-L1-Fc fusion protein inhibited CTLs-mediated platelet destruction in ITP in vitro. PD-1 promoter hypermethylation in CD8+ T cells was found in ITP patients, resulting in decreased PD-1 expression. The demethylating agent decitabine at a low dose was proved to restore the methylation level and expression of PD-1 on CD8+ T cells and reduce the cytotoxicity of CTLs of ITP patients. The phosphorylation levels of phosphatidylinositol 3-kinase (PI3K) and AKT in CD8+ T cells were significantly downregulated by low-dose decitabine. Furthermore, blocking PD-1 could counteract the effect of low-dose decitabine on CTLs from ITP patients. Therefore, our data suggest that the aberrant PD-1/PD-L1 pathway is involved in the pathophysiology of ITP and enhancing PD-1/PD-L1 signaling is a promising therapeutic approach for ITP management. Our results reveal the immunomodulatory mechanism of low-dose decitabine in ITP by inhibiting CTLs cytotoxicity to autologous platelets through PD-1 pathway. [ABSTRACT FROM AUTHOR]

Background. Evidence has suggested the functional role of exosomal miRNAs in cancer diagnosis. This study aimed to determine whether the serum exosomal biomarkers can improve the diagnosis of patients with non-small-cell lung cancer (NSCLC). Materials and Methods. The exosomes were extracted from the serum of NSCLC patients (n = 235) and healthy donors (n = 231) using ultracentrifugation and then were evaluated by using transmission electron microscopy, qNano, and western blotting. The serum exosomal miRNA expression was validated using qPCR. Results. Exosomal miR-620 was significantly reduced in NSCLC and early-stage NSCLC patients (P < 0.0001) when compared to that of healthy controls, with an area under the curve (AUC) of 0.728 and 0.707, respectively. Exosomal miR-620 expression showed an association with drinking (P = 0.008) and distant metastasis (P = 0.037). Additionally, the downregulated exosomal miR-620 showed association with chemotherapeutic effect (P = 0.044). Conclusion. These findings suggest the serum exosomal miR-620 as a promising diagnostic and prognostic noninvasive biomarker in NSCLC patients. [ABSTRACT FROM AUTHOR]

Using the surface molecular imprinting technique, a thermo-sensitive molecularly imprinted fluorescent sensor was constructed for bovine hemoglobin (BHb) detection with the silanized carbon dots (CD@SiO2) as fluorescent signal, N-isopropylacrylamide as monomer sensitive to temperature, and BHb as template. The silanized carbon dots coated by the molecularly imprinted polymer (CD@SiO2@MIP) were characterized by high-resolution transmission electron microscopy, Fourier transform infrared spectroscopy, and fluorescence spectroscopy. Owing to the combination of the strong fluorescence sensitivity of CDs and the high selectivity of the molecular imprinting shell, the prepared sensor showed good recognition and detection performance to the target protein BHb, with a linear range of 0.31–1.55 μM and a detection limit of 1.55 μM. Furthermore, the sensor was utilized to detect the content of BHb in real urine with a recovery of 98.6–100.5%. The CD@SiO2@MIP sensors present a high potential for applications in the detection of BHb in biological systems. [ABSTRACT FROM AUTHOR]

Background: Small nuclear RNA (snRNA) levels are extremely variable across a wide range of biological conditions. SnRNAs could potentially regulate alternative splicing to drive genetic, dysplastic and neoplastic disease, which might be the main reason for mRNA profile alteration in tumor educated platelets (TEPs). Methods: Platelets were isolated from the plasma of lung cancer patients and healthy donors by low-speed centrifugation and subjected to RNA isolation. SnRNA U1, U2, U5 levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Exosomes were isolated by ultracentrifugation and identified by qNano. Results: TEP U1, U2, U5 levels were significantly decreased in patients with lung cancer as well as with early stage patients, their downregulation was correlated with lung cancer progression, possessing favorable diagnostic efficiency. More importantly, TEP U1, U2 and U5 levels were closely correlated between paired exosomes and TEP from treated patients but not from untreated ones, and U1, U5 but not U2 in platelets were elevated by apo-exosomes. Conclusion: Tumor educated platelet small nuclear RNAs are downregulated and act as promising biomarkers in lung cancer. [ABSTRACT FROM AUTHOR]

The development of 3D print technology provided an opportunity to achieve fast and accurate fabrication of wearable sensor arrays. In this paper, high-sensitivity flexible and stretchable silver-coated carbon nanotube (Ag@CNT) wearable strain sensor arrays are fabricated using 3D printing technology and composite nanomaterial synthesis. Ag@CNTs with uniform and compact particles were synthesized with different sizes of carbon nanotubes (CNTs) using a reduction method. Strain sensor arrays were fabricated accurately and efficiently with the aid of 3D printed molds. Sensors with different Ag@CNTs were then compared comprehensively, and it was found that the Ag@CNT (short) sensor, which had a gauge factor (GF) of 62.8 in the 0% to 14.44% stretch range and a GF of 831.3 in the 14.44% to 21.11% stretch range, can significantly enhance the detection of small movements. These wearable strain sensor arrays were utilized in the application of traditional Chinese medicine pulse diagnosis and gesture recognition. [ABSTRACT FROM AUTHOR]