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Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and fibromyalgia have overlapping neurologic symptoms particularly disabling fatigue. This has given rise to the question whether they are distinct central nervous system (CNS) entities or is one an extension of the other. To investigate this, we used unbiased quantitative mass spectrometry-based proteomics to examine the most proximal fluid to the brain, cerebrospinal fluid (CSF). This was to ascertain if the proteome profile of one was the same or different from the other. We examined two separate groups of ME/CFS, one with (n=15) and one without (n=15) fibromyalgia. We quantified a total of 2,083 proteins using immunoaffinity depletion, tandem mass tag isobaric labeling and offline two-dimensional liquid chromatography coupled to tandem mass spectrometry, including 1,789 that were quantified in all the CSF samples. ANOVA analysis did not yield any proteins with an adjusted p-value < 0.05. This supports the notion that ME/CFS and fibromyalgia as currently defined are not distinct entities.

The burden imposed by the COVID-19 pandemic deferentially interferes with the outcomes of clinical trials of aging and dementia. We examined the impact of the lockdown on cognitive impairment due to Alzheimer’s Disease (AD), anxiety, and COVID-19-related stress in participants from the Translational Biomarkers In Aging and Dementia (TRIAD) cohort using neuropsychiatric assessments, tau and amyloid PET. We found that, before the lockdown, anxiety was higher in cognitively impaired individuals (CI) and positively associated with brain tau load. However, during the lockdown, anxiety increased only in the cognitively unimpaired (CU) and was positively associated with COVID-19 related stress. Interestingly, we found that in patients, tau load was anti-correlated with higher anxiety during lockdown. Our findings contribute to a framework for interpreting the effects of the pandemic on neuropsychiatric symptoms among clinical trial participants. Collectively, our results suggest that caregivers are more vulnerable to external stressors than patients.

Microglial activation is an early phenomenon in Alzheimer’s disease (AD) that may occur prior to and independently of amyloid-β (Aβ) aggregation. Recent studies in transgenic animal models suggest that the apolipoprotein E ε4 (APOEε4) allele may be a culprit of early microglial activation in AD. However, it is unclear whether the APOEε4 genotype is associated with microglial reactivity in the living human brain. Here, we tested whether APOEε4 carriership is associated with microglial activation in individuals across the aging and AD spectrum. We studied 118 individuals who had positron emission tomography (PET) for Aβ ([18F]AZD4694), tau ([18F]MK6240), and microglial activation ([11C]PBR28), as well as clinical, genetic, and magnetic resonance imaging data. We found that APOEε4 carriership was associated with increased microglial activation mainly in early Braak-staging regions within the medial temporal cortex, and this effect of APOEε4 was independent of Aβ and tau deposition. Furthermore, microglial activation mediated the Aβ-independent effects of APOEε4 on downstream tau accumulation, neurodegeneration, and clinical impairment. Interestingly, the physiological distribution of APOE mRNA expression, obtained from the Allen Human Atlas, predicted the patterns of APOEε4-related microglial activation in our population, suggesting that the deleterious effects of APOEε4 occur at the level of gene expression. These results support a model in which the APOEε4 has Aβ-independent effects on AD pathogenesis by activating microglia in brain regions associated with early tau deposition. Our findings provide a rationale for the development of novel AD therapies targeting the interplay between ApoE and neuroinflammation.

Two new cycloartane triterpenoids, (24 R)-cycloartane-3β,24,25,30-tetrol (1) and (24 R)-24,25,30-trihydroxy-9,19-cycloartane-3-one (2), along with three known compounds (3-5) were isolated from leaves and twigs of Aphanamixis polystachya. The new compounds were elucidated based on comprehensive spectroscopic analysis, including 1 D, 2 D NMR and HREIMS. The in vitro cytotoxic activities evaluation of five human cancer cell lines revealed that compound 1 exhibited cytotoxic activity on all of tested human cancer cell lines, while compound 2 only had specific activity on SMMC-7721 cell line.

Large numbers of cells are generally required for quantitative global proteome profiling due to surface adsorption losses associated with sample processing. Such bulk measurement obscures important cell-to-cell variability (cell heterogeneity) and makes proteomic profiling impossible for rare cell populations (e.g., circulating tumor cells (CTCs)). Here we report a surfactant-assisted one-pot sample preparation coupled with mass spectrometry (MS) method termed SOP-MS for label-free global single-cell proteomics. SOP-MS capitalizes on the combination of a MS-compatible nonionic surfactant, n-Dodecyl-β-D-maltoside, and hydrophobic surface-based low-bind tubes or multi-well plates for ‘all-in-one’ one-pot sample preparation. This ‘all-in-one’ method including elimination of all sample transfer steps maximally reduces surface adsorption losses for effective processing of single cells, thus improving detection sensitivity for single-cell proteomics. This method allows convenient label-free quantification of hundreds of proteins from single human cells and ~1200 proteins from small tissue sections (close to ~20 cells). When applied to a patient CTC-derived xenograft (PCDX) model at the single-cell resolution, SOP-MS can reveal distinct protein signatures between primary tumor cells and early metastatic lung cells, which are related to the selection pressure of anti-tumor immunity during breast cancer metastasis. The approach paves the way for routine, precise, quantitative single-cell proteomics., Tsai, Zhang, Scholten et al. develop a surfactant- assisted one-pot sample preparation coupled with mass spectrometry method (SOP-MS) for label-free global single-cell proteomics. This method allows researchers to measure hundreds of proteins from single human cells, suggesting its utility for quantitative single-cell proteomics.

The technology of wind power is being widely developed worldwide. Ensuring the reliable operation of wind turbine systems is of significance. A popular tool to identify the potential risk of an eng...

Nanotechnology gives rise to new breakthroughs and developments in various fields. The applications of advanced nanotechnology may resolve the current technical problems encountered in stem cell research. Nanotechnology has gained significant attention in both academic research and the biomedical industry in recent years. In this mini-review article, the progress of nanotechnology-aided stem cell studies has been surveyed, and the in vitro and in vivo applications of nanotechnology have been introduced. The in vitro studies are divided into three categories: isolation, detection, and regulation. The progress of in vivo studies and trends in biomedical applications have also been addressed.

HIV/AIDS pandemic remains the world's most severe public health challenge, especially for HIV/AIDS immunological nonresponders (HIV/AIDS-INRs), who tend to have higher mortality. Due to the advantages in promoting patients' immune reconstitution, Traditional Chinese medicine (TCM) has become one of the mainstays of complementary treatments for HIV/AIDS-INRs. Given that effective TCM treatments largely depend on precise syndrome differentiation, there is an increasing interest in exploring biological evidence for the classification of TCM syndromes in HIV/AIDS-INRs. In our study, to identify the typical HIV/AIDS-INRs syndrome, an epidemiological survey was first conducted in the Liangshan prefecture (China), a high HIV/AIDS prevalence region. The key TCM syndrome, Yang deficiency of spleen and kidney (YDSK), was evaluated by using a tandem mass tag combined with liquid chromatography-tandem mass spectrometry (TMT-LC-MS/MS). A total of 62 differentially expressed proteins (DEPs) of YDSK syndrome compared with healthy people were screened out. Comparative bioinformatics analyses showed that DEPs in YDSK syndrome were mainly associated with response to wounding and acute inflammatory response in the biological process. The pathway annotation is mainly enriched in complement and coagulation cascades. Finally, the YDSK syndrome-specific DEPs such as HP and S100A9 were verified by ELISA, and confirmed as potential biomarkers for YDSK syndrome. Our study may lay the biological and scientific basis for the specificity of TCM syndromes in HIV/AIDs-INRs, and may provide more opportunities for the deep understanding of TCM syndromes and the developing more effective and stable TCM treatment for HIV/AIDS-INRs.中文摘要艾滋病仍然是全世界最严重的公共卫生挑战, 尤其是对艾滋病免疫无应答者而言, 他们往往有更高的死亡率。由于中医药在促进患者免疫重建方面优势突出, 现已成为艾滋病免疫无应答者补充治疗的支柱之一。鉴于有效的中医药治疗基于精准的辨证, 探索艾滋病免疫重建不全中医证候分类的生物学依据备受青睐。在我们的研究中, 为了确定艾滋病免疫无应答者的中医证候分布规律, 首先在我国艾滋病高发区凉山州进行了流行病学调查。接着我们采用TMT-LC-MS/MS技术对典型中医证候脾肾阳虚证进行了蛋白组学研究, 筛选出62种差异表达蛋白。通过生物信息分析显示, 脾肾阳虚证中的差异表达蛋白主要与生物过程中的创伤反应和急性炎症反应等有关。通路富集主要集中在补体和凝血级联等方面。最后, 利用ELISA检测方法对脾肾阳虚证候特异性蛋白HP和S100A9进行验证, 最终将这两种证候特异性蛋白确认为脾肾阳虚证的生物标记物。这为艾滋病免疫无应答中医证候的特异性奠定了生物学和科学基础, 为深入了解中医证候, 开发更有效、更稳定的中医治疗提供了更多机会。.

Effective phosphoproteome of nanoscale sample analysis remains a daunting task, primarily due to significant sample loss associated with non-specific surface adsorption during enrichment of low stoichiometric phosphopeptide. We developed a novel tandem tip phosphoproteomics sample preparation method that is capable of sample cleanup and enrichment without additional sample transfer, and its integration with our recently developed SOP (Surfactant-assisted One-Pot sample preparation) and iBASIL (improved Boosting to Amplify Signal with Isobaric Labeling) approaches provides a streamlined workflow enabling sensitive, high-throughput nanoscale phosphoproteome measurements. This approach significantly reduces both sample loss and processing time, allowing the identification of >3,000 (>9,500) phosphopeptides from 1 (10) µg of cell lysate using the label-free method without a spectral library. It also enabled precise quantification of ∼600 phosphopeptides from 100 cells sorted by FACS (single-cell level input for the enriched phosphopeptides) and ∼700 phosphopeptides from human spleen tissue voxels with a spatial resolution of 200 µm (equivalent to ∼100 cells) in a high-throughput manner. The new workflow opens avenues for phosphoproteome profiling of mass-limited samples at the low nanogram level.

A broad variety of unactivated acyclic and alicyclic substrates cleanly undergo site-selective alkenylation of unactivated C(sp3 )-H bonds with 1,2-bis(phenylsulfonyl)ethene in the presence of persulfate. This simple transformation furnishes (E)-2-alkylvinylphenylsulfones in up to 88 % yield. In contrast with the previously reported decatungstate protocol, the current method is applicable to alkenylation of sterically hindered C-H bonds. This important advantage significantly broadens the substrate scope, and is attributed to the compact size of the sulfate radical employed in the C-H activation and cleavage.

In the era of big data, the research on clustering technologies is a popular topic because they can discover the structure of complex data sets with minimal prior knowledge. Among the existing soft clustering technologies, as an extension of fuzzy c-means (FCM) algorithm, the intuitionistic FCM (IFCM) algorithm has been widely used due to its superiority in reducing the effects of outliers/noise and improving the clustering accuracy. In the existing IFCM algorithm, the measurement of proximity degree between a pair of objects and the determination of parameters are two critical problems, which have considerable effects on the clustering results. Therefore, we propose an improved IFCM clustering technique in this paper. Firstly, a novel weighted proximity measure, which aggregates weighted similarity and correlation measures, is proposed to evaluate not only the closeness degree but also the linear relationship between two objects. Subsequently, genetic algorithms are utilized for identifying the optimal parameters. Lastly, experiments on the proposed IFCM technique are conducted on synthetic and UCI data sets. Comparisons with other approaches in cluster evaluation indexes indicate the effectiveness and superiority of our method.

Background: Approximately 85% of the U.S. military active duty population is male and less than 50 years of age, with elevated levels of known risk factors for oropharyngeal squamous cell carcinoma (OPSCC), including smoking, excessive use of alcohol, and greater numbers of sexual partners, and elevated prevalence of human papilloma virus (HPV). Given the recent rise in incidence of OPSCC related to the HPV, the Department of Defense Serum Repository provides an unparalleled resource for longitudinal studies of OPSCC in the military for the identification of early detection biomarkers. Methods: We identified 175 patients diagnosed with OPSCC with 175 matched healthy controls and retrieved a total of 978 serum samples drawn at the time of diagnosis, 2 and 4 years prior to diagnosis, and 2 years after diagnosis. Following immunoaffinity depletion, serum samples were analyzed by targeted proteomics assays for multiplexed quantification of a panel of 146 candidate protein biomarkers from the curated literature. Results: Using a Random Forest machine learning approach, we derived a 13-protein signature that distinguishes cases versus controls based on longitudinal changes in serum protein concentration. The abundances of each of the 13 proteins remain constant over time in control subjects. The AUC for the derived Random Forest classifier was 0.90. Conclusions: This 13-protein classifier is highly promising for detection of OPSCC prior to overt symptoms. Impact: Use of longitudinal samples has significant potential to identify biomarkers for detection and risk stratification.

Entity linking (EL) is the task of determining the identity of textual entity mentions given a predefined knowledge base (KB). Plenty of existing efforts have been made on this task using either “local” information (contextual information of the mention in the text), or “global” information (relations among candidate entities). However, either local or global information might be insufficient especially when the given text is short. To get richer local and global information for entity linking, we propose to enrich the context information for mentions by getting extra contexts from the web through web search engines (WSE). Based on the intuition above, two novel attempts are made. The first one adds web-searched results into an embedding-based method to expand the mention’s local information, where we try two different methods to help generate high-quality web contexts: one is to apply the attention mechanism and the other is to use the abstract extraction method. The second one uses the web contexts to extend the global information, i.e., finding and utilizing more extra relevant mentions from the web contexts with a graph-based model. Finally, we combine the two models we propose to use both extended local and global information from the extra web contexts. Our empirical study based on six real-world datasets shows that using extra web contexts to extend the local and the global information could effectively improve the F1 score of entity linking.

Fluorescence sensors exhibit great potential as molecular logic gates to perform computation on a nanometer scale. For achieving the more complex artificial intelligence activities, developing complex logic gates using multitarget sensing systems with multi-input characteristics is highly desirable. Herein, a water-soluble quadruple-target fluorescence sensor that embeds a small amount (4.1 wt %) of tetraphenylethene (TPE) units into hyperbranched poly(amido amine) (TPE-HPA) has been designed. The nonfluorescent TPE-HPA could experience the fluorescence "off-on-off-on-off" by sequential addition of sodium hexametaphosphate (SHMP), Fe3+, ascorbic acid (AA), and H2O2. The as-prepared quadruple-target sensor showed good sensitivity and selectivity to SHMP, Fe3+, AA, and H2O2, and the limit of detection values were 29 nM, 20 nM, 0.66 μM, and 0.78 μM, respectively. On the basis of the multitarget sensing nature of TPE-HPA, chemical or electrochemical-induced logic gates were constructed, including YES, NOT, OR, NOR, NAND, INHIBIT, IMP, and higher logic systems.

Aphananoid A, a limonoid which features a rare C24 appendage and new 5/6/5 fused-ring framework, was obtained from Aphanamixis polystachya. The planar structure as well as the absolute configuration was identified based on extensive spectroscopic analysis and electronic circular dichroism calculations. The biogenetic pathway of aphananoid A was also speculated, which arises from the triterpene by the 3,4-seco-7,8-seco-6,8 cyclo-7,30-decarbon key pattern. In addition, bioassays indicated that aphananoid A inhibited NO production in the RAW264.7 cell line (46.80 ± 1.93%).

To translate the International Consultation of Incontinence Questionnaire (ICIQ)-bladder diary into Chinese and validate it among Chinese women with lower urinary tract symptoms. After receiving permission to translate and validate the ICIQ-bladder diary from Bristol Urological Institute, a Chinese ICIQ-bladder diary was developed through translation, re-translation and cultural adaption. Subsequently, we tested its reliability, validity and responsiveness and evaluated its optimal record duration among females with lower urinary tract symptoms. A total of 146 participants were recruited in the study. We interviewed eight women about the content and format of the ICIQ-bladder diary, and they all thought it was clear and easy to use. Nineteen women completed the ICIQ-bladder diary twice with a 2-week interval. The resulting agreement of each item fluctuated between 0.582 and 0.940. A total of 11 urologists and nurses evaluated its content validity, and the experts’ authority was 0.94 ± 0.06. The item content validity index of the ICIQ-bladder diary was 0.909–1.000, and the scale content validity index was 0.974. Another 22 women recorded their information in the ICIQ-bladder diary pre- and post-treatment, which showed a significant difference (P

The selection of appropriate renewable energy sources (RESs) for a region is a complex multi-criteria decision-making problem because the RES selection process involves many factors, such as economic, environmental, technological and societal. Hence, to address this problem, this paper proposes a multistage framework for selecting a suitable RES alternative by integrating picture linguistic fuzzy numbers (PLFNs), preference ranking organization method for enrichment evaluations II (PROMETHEE II) and prospect theory (PT). First, PLFNs are used to describe the evaluation information. Second, using the proposed picture linguistic fuzzy weighed Heronian distance measurement, this paper proposes an extended maximizing deviation method that can capture the interrelationships among criteria. Third, an extended PROMETHEE II, which considers the bounded rationality of decision-makers, combined with PT is developed. Finally, the proposed framework solves a RES selection problem in northwest of China. The result shows solar energy is the best choice, followed by wind, hydro and biomass energy. Sensitivity analysis is conducted to explore the effects of the parameters on the results. The advantages of the proposed method are verified through a comparative analysis.

“Calcium hydroxide [Ca(OH)2]” is a medicament frequently used for antimicrobial purposes in endodontic procedures, or it is used as a toxic-waste adsorbent in industry. Ca(OH)2 particles produced through conventional methods are size untunable and have a wide size distribution and polygonal shape. In this paper, a novel and facile approach involving template-mediated synthesis and two-step ion exchange is proposed for uniform size Ca(OH)2 composite particles generation. “Sodium-alginate (Na-alginate)” was used as a precursor, and monodisperse Na-alginate emulsions were formed through needle droplet or droplet microfluidic technology. After the first ion exchange step with the Ca2+ ions, “calcium-alginate (Ca-alginate)” particles were obtained. The Ca-alginate particles were intermediate reaction products and were designed to be the templates for ensuring the spherical shape and size of products. The OH− ions were used for the second ion exchange step to fabricate Ca(OH)2 composite particles. The results revealed that the Ca(OH)2 composite particles were size tunable, had a spherical shape, and were monodisperse (with a relative standard deviation of less than 8%). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay revealed that the Ca(OH)2 composite particles were potential biocompatible materials.

Two dipolar molecules based on a thieno-imidazole core, AI109 and AI112, were developed to study the effect of imparting polarity on the hole transport properties in inverted perovskite solar cells (PSCs). These hole transport materials (HTMs) exhibit comparable optoelectronic properties but distinct film morphology and charge transport characteristics. Besides, the new materials with very low concentrations (1 mg mL−1) are able to form smooth and continuous films. The PSCs based on AI109 and AI112 without any dopants and additional interlayers have achieved increased power conversion efficiencies of 13.32% and 13.42%, respectively, compared to those of the standard HTMs, 2,2′,7,7′-tetrakis(N,N′-di-p-methoxyphenylamino)-9,9′-spirobifluorene [Spiro-OMeTAD, (11.62%)] and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate [PEDOT:PSS, (12.01%)]. The excellent hole mobility and the superior film morphology of the AI-HTMs account for their higher efficiencies.

Purpose The number of smartphone users has increased with the maturity of mobile networks, which has not only led to a new lifestyle but has also facilitated the development of mobile application services. Smartphones are regarded as essential communication devices. Currently, diverse groups of people are considering using mobile payment services. Thus, the motives for using mobile payment as well as individual motives for continuing usage are of great research interest. The purpose of this paper is to examine the behavioral motivations underlying individual intentions to continue using mobile payment. Design/methodology/approach To explore the factors affecting the intention to use mobile payment services, this study constructed a theoretical framework based on cost-benefit theory that also considers social influences to form an integrated research model that explains the intentions of individuals to use mobile payment services. Online questionnaires were used to evaluate individuals with experience using mobile payment services. A total of 302 questionnaires were collected. Structural equation modeling was employed to assess the relationships among factors included in the research model. Findings Perceived value, social norms and social self-image played crucial roles in the intention to use mobile payment services. Furthermore, perceived benefits (relative advantage and service compatibility) and perceived costs (security risks and perceived fees) determined users’ perceived value. Social self-image positively affected users’ perceived value; in the context of a mobile-oriented information system, the ability of a mobile payment service to satisfy a user’s demands with respect to social self-image influenced the user’s perceived value of using such services. Originality/value This study contributes to a theoretical understanding of factors that explain users’ intention to use mobile payment services.

Alkyl–alkenyl coupling reaction between unactivated alkyl iodides and 2-arylalkenylboronic acids utilizing a Pd/light combined system was studied. This reaction provided 2-alkylarylalkenes in good yields. It is proposed that in this reaction alkyl radicals are formed by SET from a Pd catalyst to alkyl iodides, which then undergo addition reactions to form C–C double bonds of alkenyl boronic acids and the subsequent β-fragmentation of boronyl radicals leads to the formation of alkyl-substituted arylalkenes.

We perform a detailed analysis of the magnetotransport and de Haas-van Alphen (dHvA) oscillations in crystal PdGa which is predicted to be a typical chiral Fermion semimetal from CoSi family holding a large Chern number. The unsaturated quadratic magnetoresistance (MR) and nonlinear Hall resistivity indicate that PdGa is a multi-band system without electron-hole compensation. Angle-dependent resistivity in PdGa shows weak anisotropy with twofold or threefold symmetry when the magnetic field rotates within the (1$\bar{1}$0) or (111) plane perpendicular to the current. Nine or three frequencies are extracted after the fast Fourier-transform analysis (FFT) of the dHvA oscillations with B//[001] or B//[011], respectively, which is confirmed to be consistent with the Fermi surfaces (FSs) obtained from first-principles calculations with spin-orbit coupling (SOC) considered., 8 pages, 7 figures

The soil microbial fuel cell (SMFC) is a new device that was originally designed to generate electricity from organic matter in soil using microorganisms. Currently, SMFC based biosensors are emerging as a new and promising research direction for real-time and rapid monitoring of soil quality or soil pollution. Compared to conventional biosensors, SMFC based biosensors exhibit advantages such as low-cost, simple design, in-situ, and long-term self-powering monitoring, which makes it become attractive devices for in-situ long-term soil quality or soil pollution monitoring. Thus, this review aims to provide a comprehensive overview of SMFC based biosensors. In this review, different prototypes of SMFC based biosensors developed in recent years are introduced, the biosensing mechanisms and the roles of SMFC are highlighted, and the emerging applications of these SMFC based biosensors are discussed. Since the SMFC based biosensors are applied in open-air conditions, the effects of different environmental factors on the biosensing response are also summarized. Finally, to further expand the understanding and boost the practical application of the SMFC based biosensors, future perspectives including fundamental mechanism exploration and investigation of the full-scale application are proposed.

Astrocytes can adopt multiple molecular phenotypes in the brain of Alzheimer’s disease (AD) patients. Here, we studied the associations of cerebrospinal fluid (CSF) glial fibrillary acidic protein (GFAP) and chitinase-3-like protein 1 (YKL-40) levels with brain amyloid-β (Aβ) and tau pathologies. We assessed 121 individuals across the aging and AD clinical spectrum with positron emission tomography (PET) brain imaging for Aβ ([18F]AZD4694) and tau ([18F]MK-6240), as well as CSF GFAP and YKL-40 measures. We observed that higher CSF GFAP levels were associated with elevated Aβ-PET but not tau-PET load. By contrast, higher CSF YKL-40 levels were associated with elevated tau-PET but not Aβ-PET burden. Structural equation modeling revealed that CSF GFAP and YKL-40 mediate the effects of Aβ and tau, respectively, on hippocampal atrophy, which was further associated with cognitive impairment. Our results suggest the existence of distinct astrocyte biomarker signatures in response to brain Aβ and tau accumulation, which may contribute to our understanding of the complex link between reactive astrogliosis heterogeneity and AD progression.

The therapeutic effect of CAR-T is often accompanied by sCRS, which is the main obstacle to the promotion of CAR-T therapy. The JAK1/2 inhibitor ruxolitinib has recently been confirmed as clinically effective in maintaining control over sCRS, however, its mechanism remains unclear. In this study, we firstly revealed that ruxolitinib significantly inhibited the proliferation of CAR-T cells without damaging viability, and induced an efficacy-favored differentiation phenotype. Second, ruxolitinib reduced the level of cytokine release not only from CAR-T cells, but also from other cells in the immune system. Third, the cytolytic activity of CAR-T cells was restored once the ruxolitinib was removed; however, the cytokines released from the CAR-T cells maintained an inhibited state to some degree. Finally, ruxolitinib significantly reduced the proliferation rate of CAR-T cells in vivo without affecting the therapeutic efficacy after withdrawal at the appropriate dose. We demonstrated pre-clinically that ruxolitinib interferes with both CAR-T cells and the other immune cells that play an important role in triggering sCRS reactions. This work provides useful and important scientific data for clinicians on the question of whether ruxolitinib has an effect on CAR-T cell function loss causing CAR-T treatment failure when applied in the treatment of sCRS, the answer to which is of great clinical significance.

Background. Chronic kidney disease (CKD) is a critical public health issue with a huge financial burden for both patients and society worldwide. Unfortunately, there are currently no efficacious therapies to prevent or delay the progression of end-stage renal disease (ESRD). Traditional Chinese medicine practices have shown that Cordyceps militaris (C. militaris) mycelia have a variety of pharmacologically useful properties, including antitumor, immunomodulation, and hepatoprotection. However, the effect of mycelial C. militaris on CKD remains unclear. Methods. Here, we investigated the effects of C. militaris mycelia on mice with CKD using four types of media: HKS, HKS with vitamin A (HKS + A), CM, and CM with vitamin A (CM + A). Results. The results at day 10 revealed that the levels of blood urea nitrogen (BUN) were significantly lower in the HKS (41%), HKS + A (41%), and CM + A (34%) groups compared with those in the corresponding control groups (nephrectomic mice). The level of serum creatinine in the HKS + A group decreased by 35% at day 10, whereas the levels in the HKS and CM + A groups decreased only by 14% and 13%, respectively, on day 30. Taken together, this is the first report using four new media (HKS, HKS + A, CM, and CM + A medium) for C. militaris mycelia. Each medium of mycelial C. militaris on CKD exhibits specific effect on BUN, serum creatinine, body weight, total protein, and uric acid. Conclusions. Taken together, this is the first report using four new media (HKS, HKS + A, CM, and CM + A medium) for C. militaris mycelia. Each medium of mycelial C. militaris on CKD exhibits specific effects on BUN, serum creatinine, body weight, total protein, and uric acid. We concluded that treatment with C. militaris mycelia cultured in HKS or CM + A medium could potentially prevent the deterioration of kidney function in mice with CKD.

Karrikins are active components of smoke that can promote seed germination and regulate seedling morphogenesis. However, the role of karrikins as alleviators of abiotic stress remains largely elusive. In this study, we examined whether exogenous application of karrikin1 (KAR1) might improve drought tolerance in creeping bentgrass (Agrostis stolonifera cv. PennA4), and investigated the underlying mechanism. We found that exogenous application of 100 nM KAR1 enhanced drought tolerance in creeping bentgrass, as manifested by significant increases in leaf relative water content, efficiency of photosystem II, leaf chlorophyll content, proline content, and membrane stability, as well as significantly enhanced activities of antioxidant enzymes. RT–PCR analysis indicated that improved drought stress tolerance by application of KAR1 might be related to upregulation expression of karrikin-responsive genes (KAI2, MAX2 and AFL1), transcription factors (ABF3, bHLH148, MYB13 and DREB2A), antioxidant defense genes (Cu/Zn-SOD, APX2, CAT1, and POD2), and downregulation expression of chlorophyll-degradation genes (PPH and Chl-PRX). These findings suggest that KAR1 may promote the drought tolerance of creeping bentgrass by activating karrikin-responsive genes and transcription factors, enhancing proline accumulation and antioxidant capacity, and suppressing leaf senescence under prolonged drought stress.

Exosomes are a promising noninvasive tumor biomarker for cancer diagnosis and classification. However, efficient capture and precise analysis of exosomes in complex biological samples remain challenging. Here, sensitive profiling of exosomes with an integrated separation-detection strategy of 37 min is performed based on boronic acid-directed coupling immunoaffinity. The modification of g-C3N4 nanosheets with boronic acid (BCNNS) contributes to antibody binding under physiological conditions, which is accompanied by fluorescence enhancement. When exosomes are captured by an antibody equipped with BCNNS, a decrease in fluorescence can be induced; moreover, using the dispersion property of BCNNS, the exosomes can be separated by a simple centrifugation step. The protocol shows a favorable sensitivity with a detection limit of 2484 particles/mL. By changing only the fused antibody, exosome phenotype information profiling can be achieved, and exosomes derived from four different cell lines (HeLa, HepG2, MCF-7, and MCF-10A) can be successfully distinguished. More significantly, the positive prediction accuracy results reach 100% for serum samples from different individuals and have the advantage of multiple parameters; thus, the method has great potential in noninvasive diagnosis and point-of-care testing.

This study explored the factors that affect the intention of users to continue using mobile learning (m-learning) applications (apps). The influence of habit on user behavior toward information systems has been extensively discussed in the literature, but its role in the continuance of users when it comes to their usage of apps, especially m-learning apps, has rarely been reported. To obtain a comprehensive understanding of behaviors regarding the use of m-learning apps, this study constructed a theoretical research framework based on expectation confirmation theory and flow theory by considering habit as a moderating variable. Online questionnaires were administered to users of m-learning apps in Taiwan and data were analyzed through a structural equation modeling approach. The results indicated that the intention of users to continue using m-learning apps was influenced by satisfaction, perceived usefulness, and flow experience. Expectation confirmation affected user satisfaction and perceived usefulness. Differences existed in the intention to continue usage between users with strong and weak habits. In addition, perceived usefulness, expectation confirmation, and flow experience had direct and positive effects on satisfaction. The implications of these findings were discussed.

Chronic kidney disease (CKD) is a critical public health issue with a huge financial burden for both patients and society worldwide. Unfortunately, there are currently no efficacious therapies to prevent or delay the progression of end-stage renal disease (ESRD). Traditional Chinese medicine practices have shown thatHere, we investigated the effects ofThe results at day 10 revealed that the levels of blood urea nitrogen (BUN) were significantly lower in the HKS (41%), HKS + A (41%), and CM + A (34%) groups compared with those in the corresponding control groups (nephrectomic mice). The level of serum creatinine in the HKS + A group decreased by 35% at day 10, whereas the levels in the HKS and CM + A groups decreased only by 14% and 13%, respectively, on day 30. Taken together, this is the first report using four new media (HKS, HKS + A, CM, and CM + A medium) forTaken together, this is the first report using four new media (HKS, HKS + A, CM, and CM + A medium) for