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Background: Glioblastomas are lethal brain tumors under the current combinatorial therapeutic strategy that includes surgery, chemo- and radio-therapies. Extensive changes in the tumor microenvironment is a key reason for resistance to chemo- or radio-therapy and frequent tumor recurrences. Understanding the tumor-nontumor cell interaction in TME is critical for developing new therapy. Glioblastomas are known to recruit normal cells in their environs to sustain growth and encroachment into other regions. Neural progenitor cells (NPCs) have been noted to migrate towards the site of glioblastomas, however, the detailed mechanisms underlying glioblastoma-mediated NPCs' alteration remain unkown. Methods: We collected EVs in the culture medium of three classic glioblastoma cell lines, U87 and A172 (male cell lines), and LN229 (female cell line). U87, A172, and LN229 were co-cultured with their corresponding EVs, respectively. Mouse NPCs (mNPCs) were co-cultured with glioblastoma-derived EVs. The proliferation and migration of tumor cells and mNPCs after EVs treatment were examined. Proteomic analysis and western blotting were utilized to identify the underlying mechanisms of glioblastoma-derived EVs-induced alterations in mNPCs. Results: We first show that glioblastoma cell lines U87-, A172-, and LN229-derived EVs were essential for glioblastoma cell prolifeartion and migration. We then demonstrated that glioblastoma-derived EVs dramatically promoted NPC proliferation and migration. Mechanistic studies identify that glioblastoma-derived EVs achieve their functions via activating PI3K-Akt-mTOR pathway in mNPCs. Inhibiting PI3K-Akt pathway reversed the elevated prolfieration and migration of glioblastoma-derived EVs-treated mNPCs. Conclusion: Our findings demonstrate that EVs play a key role in intercellular communication in tumor microenvironment. Inhibition of the tumorgenic EVs-mediated PI3K-Akt-mTOR pathway activation might be a novel strategy to shed light on glioblastoma therapy. 9isrUz1Ju_9yzYdEacJBzA Video Abstract [ABSTRACT FROM AUTHOR]

• Astrocyte-derived extracellular vesicles (AEVs) are key components of CNS microenvironment. • AEVs serve as a crucial aggravating factor of CNS disorders by inducing neuroinflammation and neurotoxicity. • AEVs exhibit neuroprotective//regenerative effects by alleviating inflammation/apoptosis and enhancing neuroplasticity. • AEVs contain various neurological disorder-related molecules that can be applied as diagnostic biomarkers. • AEVs are potential therapeutic targets for neurological disorder treatment or prevention. Recent studies suggest that astrocytes released a great quantity of extracellular vesicles (AEVs) to communicate with other brain cells. Under pathological conditions, AEVs are widely associated with the pathogenesis of neurobiological diseases by horizontally transferring pathogenic factors to neighboring cells or peripheral immune cells. Their beneficial role is also evident by the fact that they are involved in neuroprotection and neuroregeneration through alleviating apoptosis, maintaining neuronal function, and repairing neural injuries. The strong association of AEVswith neurological disorders makes AEVs a promising target for disease diagnosis, treatment, and prevention. The identification of disease-specific cargos in AEVs isolated from the patients' biofluids suggests AEVs as an attractive platform for biomarker development. Furthermore, the inhibition of inflammatory/toxic AEV release and the preservation of neuroprotective AEV release have been considered as potential therapeutic strategies in CNS disorder treatment and prevention, respectively. Here, we summarize the biological roles of AEVs as pathological contributors, protective/regenerative factors, and potential diagnostic biomarkers and therapeutic targets for neurological disorders, with a focus on recent progresses and emerging concepts. [ABSTRACT FROM AUTHOR]

The addition of reagents into preformed droplets is a crucial yet intricate task in droplet-based applications where sequential reactions is required. Pico-injection offers high throughput and robustness in accomplishing this task, but the existing pico-injection techniques work in an indiscriminate manner, making it difficult to target particular groups of droplets. Here we report image-activated pico-injection (imgPico) for label-free, on-demand reagent supplementation into droplets. The imgPico detects the droplets of interest by real-time image analysis and makes decisions for the downstream pico-injection operation. We studied the performance of different algorithms for the image analysis and optimized the experimental settings of the imgPico. In the validation experiment, the imgPico successfully injected fluorescent dyes into droplets encapsulating one, two, and three cells, respectively, as expected. We further demonstrated the utility of imgPico by targeting droplets encapsulating single cells in droplet-based single-cell RNA sequencing (scRNA-seq) using exceedingly high cell density, and the results showed that the imgPico effectively reduced the presence of doublets in the scRNA-seq data. With the merits of being label-free and versatile, the imgPico represents a technical advance with potential applications in single-cell analysis. [Display omitted] • Adding reagents into preformed droplets is an important but sophisticated task in droplet-based applications. • A method for label-free, on-demand reagent supplementation into droplets is reported. • The method detects droplets of interest by real-time image analysis for downstream pico-injection operation. • The method shows great applications in experiments of single cell RNA sequencing. [ABSTRACT FROM AUTHOR]

The gelatinization phenomena and crystalline structure of maize starch gelatinized in pure glycerol were investigated using confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Starch granules were firstly treated in water system, CLSM and SEM micrographs displayed that they were completely broken and the characteristic birefringence of the starch granules disappeared at 70 °C. As for pure glycerol system, the starch granules swelled but maintained granular shape with the increasing of temperature. The crystalline structure of starch granules was partially destroyed at 130 °C and completely destroyed at 140 °C. The DSC thermogram showed that the gelatinization temperature of starch in glycerol started at 123.7 °C, peaked at 128.4 °C, and concluded at 135.2 °C. The X-ray diffractograms indicated that the crystalline structure of maize starch was partially destroyed at 130 °C and completely destroyed at 140 °C. Thus, glycerol served an alternative solvent to destroy crystalline structure of maize starch, which may be helpful for hydrolysis of starch granules by amylase in food industry. Overview of structural destruction of maize starch treated in pure glycerol. Image 1099 • CLSM was used for the exploring the changes of morphologies and crystalline structure of maize starch during gelatinization. • The phase transition temperature of maize starch in glycerol was significantly higher than that in water. • Crystalline structure of maize starch was partially destroyed at 130 °C and completely destroyed at 140 °C. • Maize starch granules gelatinized in glycerol maintained granular morphology rather than gelatinized into paste. • A promising approach was proposed for producing thermoplastic materials. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the leading cause of dementia and is rapidly becoming one of the most costly, fatal diseases, which is typically discovered in the late stage of molecular pathology, at which point medication intervention is irreversible. As a result, there is an urgent need for a low-cost, least-invasive way of screening cognitive impairment, with the goal of identifying persons at risk of AD. Mild cognitive impairment (MCI) has been described as a transitional state between normal cognitive aging and AD. Early detection and timely tracking of MCI can to some extent prevent the progression towards AD. We found a population in Northwestern China has a comparatively high prevalence of MCI. Continued education, consistent exercise, and a secure financial situation can all help older people maintain cognitive function. Due to the critical role of circulating microRNAs in intercellular signaling and the perturbations thereof, their investigation has assumed paramount significance in elucidating various pathological conditions. Numerous investigations have substantiated the significance of circulating miRNAs specifically in MCI. Here, we evaluated miR-483-5p (Area Under the Curve (AUC) is 0.901, sensitivity 79.2 % and specificity 100 %) and miR-502-5p (AUC is 0.872, sensitivity 79.2 % and specificity 83.3 %), which were derived from plasma exosomes and maintained at high levels in elderly people with MCI, could be employed as promising noninvasive biomarkers. • Northwestern Chinese community shows a high prevalence of MCI. • Learning, exercise, and financial stablility can help preserve cognitive function in the elderly. • Exosome miR-483-5p/-502-5p effectively discriminates MCI in non-hospitalized community elderly without acute disease. [ABSTRACT FROM AUTHOR]

Three advanced methods, high performance affinity chromatography (HPAC), surface plasmon resonance (SPR) and surface plasmon resonance imaging (SPRi) were compared and evaluated for determining the drug-cyclodextrin (CD) interactions herein. In total, 18 sparingly soluble drugs were selected for this comparative study. The three methods share a unique connection in the working principles and strategies. The same strategies of CD fixation onto solid phase were used in HPAC and SPR for the measurements, whereas, the SPR and SPRi share identical working principles. However, whilst these relationships are evident, no strong correlation was found between kinetic constants obtained from the three methods: Four drugs, namely, prednisolone, pseudolaric acid B, diazepam and gramisetron failed to show any response on SPR, whereas, the kinetics parameters from SPRi and HPAC were successfully measured. From a comparative review of all the kinetic data, random results without any trends were observed (ka, kd and K A ) regardless of the relationships between the three methods: It is apparent that the measurement conditions (volume, flow rate, buffers), non-specific adsorption and experimental procedures had a strong impact on the generated data. The relative advantages and limitations of each method are critically presented on the basis of generated data. This comparative study provides a basis to further upgrade these techniques for confident measurement of drug-CDs interactions. [ABSTRACT FROM AUTHOR]

Abstract: A solid modified electrode based on PW11O39Fe(III)(H2O)4− (PW11Fe) and chitosan (CS) was fabricated by sol–gel process via immobilization of PW11Fe, adsorbed on CS, onto the surface of a glassy carbon (GC) or a graphite (C) electrode with methyltrimethoxysilane as a cross-linking agent. After characterization by scanning electron microscope (SEM) and transmission electron microscope (TEM), the electrochemical characteristics of the PW11Fe/CS/C system and its electrocatalytic activity towards H2O2 reduction were investigated using electrochemical methods such as cyclic voltammetry and alternating current impedance. It was found that the PW11Fe/CS/C system still retained the electrochemical properties of the PW11Fe and its eletrocatalytic activity towards H2O2 reduction in homogeneous solution. Application of the PW11Fe/CS/C system in electrocatalytic degradation of nitrobenzene (NB) revealed that 100% of NB degradation was obtained at 120min in 0.1M Na2SO4 +NaHSO4 (pH 3.5) solution containing 1mM NB. [Copyright &y& Elsevier]

Breast cancer has become the leading cause of global cancer incidence and a serious threat to women's health. Accurate diagnosis and early treatment are of great importance to prognosis. Although clinically used diagnostic approaches can be used for cancer screening, accurate diagnosis of breast cancer is still a critical unmet need. Here, we report a 4-plex droplet digital PCR technology for simultaneous detection of four small extracellular vesicle (sEV)-derived mRNAs (PGR, ESR1, ERBB2 and GAPDH) in combination with machine learning (ML) algorithms to improve breast cancer diagnosis. We evaluate the diagnsotic results with and without the assistance of the ML models. The results indicate that ML-assisted analysis exhibits higher diagnostic performance even using a single marker for breast cancer diagnosis, and demonstrate improved diagnostic performance under the best combination of biomarkers and suitable ML diagnostic model. Therefore, multiple sEV-derived mRNAs analysis coupled with ML not only provides the best combination of markers for breast cancer diagnosis, but also significantly improves the diagnostic efficiency of breast cancer. • A 4-plex droplet digital PCR is developed for multiplexed detection of sEV-derived PGR, ESR1, ERBB2 and GAPDH mRNAs for breast cancer diagnosis. • Droplet digital PCR entitles this method enough sensitivity, excellent stability, and applicability in clinic. • Multiplexed detection coupled with machine learning provides the best combination of biomarkers for improving breast cancer diagnosis. [ABSTRACT FROM AUTHOR]

• SRA exhibits the strongest capacity to compensate for drying shrinkage. • Reducing the drying shrinkage of AACGS mortar is related to the change of pore size of 2–5 nm. • The mechanism of pore distribution change caused by different admixtures is different. • The Kelvin radius of the minimum hole of AACGS mortars is calculated to be 2.11 nm. By using slag as a calcium source, high-strength alkali-activated coal gangue-slag (AACGS) cementitious material can be prepared. Given that higher drying shrinkage at room temperature is detrimental to the expanded engineering application of the material, this paper studies several methods for reducing drying shrinkage such as shrinkage-reducing admixture (SRA), polypropylene fiber (PPF), sulfate-enriched materials (gypsum, high-performance concrete expansive admixture (HCSA), U-type expansive admixture (UEA)) and water retaining admixture (WRA). Meanwhile, the mechanisms for drying shrinkage compensation were deeply analyzed by mercury intrusion porosimetry (MIP) and scanning electron microscopy (SEM). Experimental results show that the addition of admixtures to reduce the drying shrinkage of AACGS mortar is related to the change of pore size of 2–5 nm, and reduces the volume fraction of the minimum aperture. At room temperature, reducing the surface tension of pore solution, generating expansion products, increasing compressive strength and improving pore structure distribution by adding admixtures are important measures to reduce drying shrinkage. SRA exhibits the strongest capacity to compensate for drying shrinkage, followed by UEA, WRA, HCSA, PPF and gypsum. Despite better compensation for drying shrinkage with the increase in SRA dosage, the reduction of strength value becomes more drastic. The findings of this study provide substantial experimental foundations and in-depth theoretical analyses for the drying shrinkage compensation of AACGS binary cementitious materials. [ABSTRACT FROM AUTHOR]

• Emulsion with 4% protein exhibited desirable emulsion stability and less coalescence than emulsion with 2% protein. • Ultrasonic treatment was more effective on generating small and uniform crystal distribution. • Hardness of emulsions were accelerated by ultrasonic treatment during storage. • Melting enthalpy of emulsions were remarkable increased with ultrasound. Lard with a substantially reduced cholesterol content through aqueous enzyme extraction is an attractive source of lipid in healthy and nutritious emulsion food product development. The objective of this study was to elucidate the crystallization behavior (4–20 °C) of emulsions prepared from low-cholesterol lard in relation to protein emulsifier (2 and 4% whey protein isolate, WPI) and ultrasound (475 w, 5 min) treatments. The physicochemical properties and fat crystallization pattern of the emulsions were investigated. Emulsions with 4% WPI were superior to those with 2% WPI on interfacial adsorption and crystal size reduction. Ultrasonic treatment of prepared emulsions further decreased fat crystal size, promoted small and uniform crystal distribution, and slightly destabilized emulsions. Protein concentration and ultrasonic treatment had no obvious effect on crystal transition from β′ to the more stable β-form based on X-ray diffraction. The melting properties determined by differential scanning calorimetry indicated that emulsified lard had a lower onset melting temperature than bulk lard, and with ultrasound treatment, the melting enthalpy increased remarkably. The ultrasound-induced change in fat crystalline structure and emulsion meta-stability may be valuable to the manufacture of healthy, emulsion-incorporated food products. [ABSTRACT FROM AUTHOR]

This study investigated the causal effect of gut microbiota on critical pneumonia. Data came from a large-scale gut microbiota data set (n = 18,340) and the critical pneumonia genome-wide genotyping array (cases n = 2758 and controls n = 42,8607). Inverse variance weighting was used as the primary Mendelian randomization (MR) analysis method. Weighted median, MR-Egger, simple model, weighted model, and MR-Egger, were used to evaluate robustness. Sensitivity analysis used Cochran Q test, MR-Egger intercept test, and MR-PRESSO. For critical pneumonia, inverse variance weighting estimates suggested that Class Verrucomicrobiae (OR = 0.415; 95% CI: 0.207, 0.833; P = .013), Family Verrucomicrobiaceae (OR = 0.415; 95% CI: 0.207, 0.833; P = .013), Genus Akkermansia (OR = 0.415; 95% CI: 0.207, 0.833; P = .013), Genus LachnospiraceaeFCS020group (OR = 0.449; 95% CI: 0.230, 0.890; P = .021), Genus Parasutterella (OR = 0.466; 95% CI: 0.233, 0.929; P = .030), Genus Prevotella7 (OR = 0.645; 95% CI: 0.432, 0.960; P = .031), Order Verrucomicrobiales (OR = 0.415; 95% CI: 0.207, 0.833; P = .013), and Phylum Cyanobacteria (OR = 0.510; 95% CI: 0.272, 0.956; P = .036) had a reduced risk, while Family Enterobacteriaceae (OR = 2.746; 95% CI: 1.008, 7.474; P = .048), Genus RuminococcaceaeUCG003 (OR = 2.811; 95% CI: 1.349, 5.851; P = .006) and Order Enterobacteriales (OR = 2.746; 95% CI: 1.008, 7.474; P = .048) were associated with an increased risk. Sensitivity analyses confirmed that the aforementioned correlations were robust., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

The utilization of fast-growing, economically valuable woody plants with strong stress resistance, such as poplar and willow, to revegetate severely metal-contaminated mine tailings not only offers a productive and profitable use of abandoned polluted soil resources but also facilitates the phytoremediation of these polluted soils. This study examines the diversity and functional roles of endophytic fungi naturally colonizing the roots of an artificially established Populus yunnanensis forest and the naturally reclaimed pioneer species Coriaria sinica on an abandoned tailing dam in southwest China. Culture-independent analyses revealed that the root systems of both plant species were abundantly colonized by arbuscular mycorrhizal fungi and endophytic fungi, forming rich and diverse endophytic fungal communities predominantly represented by the genera Ilyonectria , Tetracladium , Auricularia , and unclassified members of Helotiales. However, the composition of root endophytic fungal communities differed significantly between the two plant species. Using a culture-dependent approach, a total of 192 culturable endophytic fungal strains were isolated from the roots. The dominant genera included Cadophora , Cladosporium , Cyphellophora , and Paraphoma, most of which were previously identified as dark septate endophytes (DSE). Six representative DSE strains were selected for further study, and significant cadmium tolerance and various plant growth-promoting traits were observed, including the solubilization of insoluble inorganic and organic phosphorus, indole-3-acetic acid (IAA) production, and siderophore synthesis. In greenhouse experiments, inoculating two DSE strains mitigated the inhibitory effects of metal-polluted tailing soil on the growth of P. yunnanensis . This was achieved by reducing heavy metal uptake in roots and limiting metal translocation to the above-ground tissues, thereby promoting plant growth and adaptability. Our findings suggest that as plants reclaim metal-polluted tailings, root-associated endophytic fungal communities also undergo natural succession, playing a critical role in enhancing the host plant's tolerance to stress. Therefore, these restored root-associated fungi, particularly DSE, are essential functional components of the root systems in plants used for tailing reclamation.

Objective: To investigate the mechanisms of the effect of Actinidia chinensis polysaccharide (ACPS) on the invasion and metastasis of gastric cancer cells., Methods: BGC-823-Luc gastric cancer cells stably transfected with a luciferase gene were used to establish an insitutransplanted tumor mouse model. A live mouse imaging system was used to observe tumor growth, and hematoxylin and eosin staining was applied to analyze tissue histopathology. Transwell and scratch wound assays were performed to examine the invasive and migratory ability of BGC-823 cells. Immunofluorescence, confocal microscopy, immunohistochemistry, and Western blot assays were used to analyze the expressions of the nuclear transcription factor-κB (NF-κB) signaling pathway and epithelial-mesenchymal transition (EMT)-related proteins., Results: ACPS significantly inhibited the growth of subcutaneously transplanted BGC-823-Luc gastric cancer tumors in nude mice and reduced inflammatory cell infiltration in tumor tissues. ACPS inhibited Epidermal Growth Factor-induced invasion, migration, and morphological changes in the cytoskeleton of BGC-823 cells. ACPS inhibited gastric cancer EMT and decreased the expression of matrix metallopeptidase 9, N-cadherin and p-NF-κB p65 in transplanted tumor tissues. ACPS inhibited the expression of matrix metalloproteinases and vascular adhesion factors in BGC-823 cells, promoted p65-NF-κB nuclear translocation, and regulated proteins associated with the NF-κB p65 pathway., Conclusions: ACPS inhibited gastric cancer invasion and metastasis both in vivo and in vitro , which evidenced the inhibition of gastric cancer EMT via regulating the NF-κB inflammatory pathway.

Background: Early recognition and accurate diagnosis are particularly important in the context of gastric cancer. This study mainly aimed to investigate primary care physicians' (PCPs') clinical behaviour and their readiness to consider investigation or referral for symptoms possibly indicative of gastric cancer., Design: Cross-sectional study., Setting: A self-administered online survey was carried out in five selected cities in the Fujian province of China between February 2022 and May 2022., Participant: PCPs working in the departments, such as Internal Gastroenterology and Hepatology, General Internal Medicine, Internal Medical Oncology Gastrointestinal Surgery or other clinical departments, have the chance to diagnose or treat patients with suspected gastric cancer., Main Outcome Measures: Percentage of PCPs identifying gastric cancer patients either by undertaking an endoscopy at the primary hospital or by referring patients to an upper-level hospital., Results: A total of 1210 complete responses were received. Nearly half of responding PCPs (46.4%) only had less than 5 years of clinical experience, and the majority worked in suburban or rural regions (64.4%). Direct access to blood tests for cancer diagnosis (77.9%), X-ray (77.2%), CT (55.7%), ultrasound (85.3%), upper gastrointestinal endoscopy (54.4%) and colonoscopy (51.9%) was common. Of the respondents, 85.5% reported that they could get specialist advice for a suspected cancer patient within 48 hours in terms of investigations and 84.0% in terms of referral. Patients' waiting time to either conduct a test or have a result was mostly less than 1 week. In patients indicative of gastric cancer, a total of 1148 (94.8%) physicians were ready to investigate cancer either by sending patients to an endoscopy test (49.7%) or referring them to an upper-level hospital (45.1%)., Conclusions: Findings indicate that PCPs in five selected cities of Southeastern China have wide and rapid access to diagnostic tests and specialist advice. Furthermore, PCPs in this region seem to have a high level of readiness to consider investigation or referral for symptoms possibly indicative of gastric cancer., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Transcription factor deregulation potently drives melanoma progression by dynamically and reversibly controlling gene expression programs. We previously identified the small MAF family transcription factor MAFG as a putative driver of melanoma progression, prompting an in-depth evaluation of its role in melanoma. MAFG expression increases with human melanoma stages and ectopic MAFG expression enhances the malignant behavior of human melanoma cells in vitro, xenograft models, and genetic mouse models of spontaneous melanoma. Moreover, MAFG induces a melanoma phenotype switch from a melanocytic state to a more dedifferentiated state. Mechanistically, MAFG interacts with the lineage transcription factor MITF which is required for the pro-tumorigenic effects of MAFG. MAFG and MITF co-occupy numerous genomic sites and MAFG overexpression influences the expression of genes harboring binding sites for the MAFG~MITF complex. These results establish MAFG as a potent driver of melanomagenesis through dimerization with MITF and uncover an unappreciated mechanism of MITF regulation., Competing Interests: Conflicts: The authors declare no financial conflicts of interest

Although many people have been vaccinated against COVID-19, infections with SARS-CoV-2 seem hard to avoid. There is a need to develop more effective vaccines and immunization strategies against emerging variants of infectious diseases. To understand whether different immunization strategies using variants sequence-based virus-like particles (VLPs) vaccines could offer superior immunity against future SARS-CoV-2 variants, our team constructed VLPs for the original Wuhan-Hu-1 strain (prototype), Delta (δ) variant, and Omicron (ο) variant of SARS-CoV-2, using baculovirus-insect expression system. Then we used these VLPs to assess the immune responses induced by homologous prime-boost, heterologous prime-boost, and sequential immunizations strategies in a mouse model. Our results showed that the pro+δ+ο sequential strategies elicited better neutralizing antibody responses. These sequential strategies also take advantage of inducing CD4 + T and CD8 + T lymphocytes proliferation and tendency to cytokine of Th1. Currently, our data suggest that sequential immunization with VLPs of encoding spike protein derived from SARS-CoV-2 variants of concern may be a potential vaccine strategy against emerging diseases, such as "Disease X".

Objective: This study aimed to investigate the level of family caregivers' (FC) burden and the extent to which patient- and caregiver-related factors influence the caregiving burden among FCs of urologic cancer (UC) patients., Method: A cross-sectional survey was conducted on caregivers of UC patients who sought cancer care. The modified caregiver strain index (MCSI) was used to assess FC burden., Results: Just over half (54.3%) of FCs had moderate/high MCSI scores (score 9-26). By demographics, FCs who were unemployed (OR = 5.55, 95%CI 1.50-20.60) and perceived their current health condition as moderate/poor (OR = 6.05, 95%CI 1.95-18.78) reported higher odds of increased FC burden. Patient performance status played a pivotal role in exacerbating FC burden, whereby the odds of higher FC burden was 13 times higher in caregivers of UC patients having an Eastern Cooperative Oncology Group (ECOG) performance rating score of 3-4 (OR = 13.06, 95%CI 1.44-111.26) than those with a score of 0. Perceived lower levels of confidence in care provision were significantly associated with a higher level of strain (OR = 6.76, 985%CI 1.02-44.90)., Conclusion: Care recipient performance status was a strong patient-related factor associated with higher FC burden regardless of duration of caregiving and other caregiver-related factors after adjusting for caregiver demographics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The COVID-19 pandemic is bringing about substantial changes in health care systems, leading to a significant shift toward telemedicine for the delivery of health care services., Objective: This study aims to examine the relationship between perceived usefulness and ease of use of telemedicine services and their association with the behavioral intention to use telemedicine., Methods: An anonymous cross-sectional survey was conducted in China. Partial least squares structural equation modeling was used to determine significant predictors of intention to use telemedicine consultation. Types of illnesses that favored seeking telemedicine consultation, as well as the most preferred platform for conducting telemedicine consultations, were also investigated., Results: In total, 1006 participants completed the survey. A total of 44.3% (n=446) reported being very likely and 49.3% (n=496) reported being likely to seek telemedicine consultation. Overall, the majority of participants expressed strong agreement or agreement regarding the perceived usefulness of telemedicine. Likewise, the majority indicated strong agreement or agreement when it came to their perception of the ease of using telemedicine. In the partial least squares structural equation modeling, perceived usefulness (β=0.322; P<.001) and perceived ease of use (β=0.118; P=.01) were significantly associated with a higher likelihood of seeking telemedicine consultation. A considerable number of participants expressed willingness to use telemedicine services for various medical conditions, particularly respiratory (n=340, 33.8%), skin (n=316, 31.4%), and musculoskeletal issues (n=316, 31.4%) while showing less interest in seeking telemedicine consultations for reproductive health (n=44, 4.4%) and cancer (n=64, 6.4%). The majority preferred video chat (n=443, 44%) and text chat (n=317, 31.5%) as their most preferred platforms for telemedicine consultation, while a smaller proportion preferred telephone (n=193, 19.2%) and email (n=53, 5.3%)., Conclusions: Telemedicine has the potential to play a larger role in China's health care system. The preferences for certain platforms over others may influence service design and implementation., (©Yulan Lin, Xiaonan Xu, Yiyang Liu, Haridah Alias, Zhijian Hu, Li Ping Wong. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 16.07.2024.)

Tuberculosis (TB) remains a major infectious disease partly due to the lack of an effective vaccine. Therefore, developing new and more effective TB vaccines is crucial for controlling TB. Mycobacterium tuberculosis ( M. tuberculosis ) usually parasitizes in macrophages; therefore, cell-mediated immunity plays an important role. The maintenance of memory T cells following M. tuberculosis infection or vaccination is a hallmark of immune protection. This review analyzes the development of memory T cells during M. tuberculosis infection and vaccine immunization, especially on immune memory induced by BCG and subunit vaccines. Furthermore, the factors affecting the development of memory T cells are discussed in detail. The understanding of the development of memory T cells should contribute to designing more effective TB vaccines and optimizing vaccination strategies.

Background: This study aimed to determine the intention and willingness-to-pay (WTP) of Chinese parents/guardians to vaccinate their children with the EV-71 vaccine. Knowledge levels about hand, foot, and mouth disease (HFMD) and the EV-71 vaccine were also investigated., Methods: A cross-sectional, self-administered online survey was conducted between November 2022 and March 2023. A stratified multi-stage random sampling method was used to recruit parents/guardians of children aged 0-5 years in southeastern China., Results: A total of 3,626 complete responses were received. The mean knowledge score of HFMD was 9.99 (±4.23) out of a total of 14 points. The majority of the participants reported a somewhat willing intent (58.8%), followed by an extremely willing intent (28.9%). Participants who did not consider the EV-71 vaccine expensive (OR = 2.94, 95%CI 2.45-3.53) perceived that the EV-71 vaccine is effective (OR = 2.73, 95%CI 1.52-4.90), and a high knowledge level of HFMD (OR = 1.90, 95%CI 1.57-2.29) had the highest significant odds of having an extremely willing intent to vaccinate their children with the EV-71 vaccine. The median (interquartile range [IQR]) of WTP for the EV-71 vaccine was CNY¥200/USD$28 (IQR CNY¥100-400/USD$14-56). The highest marginal WTP for the vaccine was mainly influenced by the perceived high cost of the vaccine. Those participants who did not consider the EV-71 vaccine expensive had more than 10 times higher odds of vaccinating their children (OR = 10.86, 95%CI 8.49-13.88). Perceived susceptibility, perceived benefits, and perceived barriers were also significant influencing factors in the highest marginal WTP., Conclusion: The findings demonstrate the importance of improving health promotion and reducing the barriers to EV-71 vaccination. Therefore, it is important to improve health promotion and reduce the barriers to EV-71 vaccination., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cheng, Zhong, Xu, Li, Xie, Lin and Zhang.)

Inactivating mutations in PTEN are prevalent in melanoma and are thought to support tumor development by hyperactivating the AKT/mTOR pathway. Conversely, activating mutations in AKT are relatively rare in melanoma, and therapies targeting AKT or mTOR have shown disappointing outcomes in preclinical models and clinical trials of melanoma. This has led to the speculation that PTEN suppresses melanoma by opposing AKT-independent pathways, potentially through noncanonical functions beyond its lipid phosphatase activity. In this study, we examined the mechanisms of PTEN-mediated suppression of melanoma formation through the restoration of various PTEN functions in PTEN-deficient cells or mouse models. PTEN lipid phosphatase activity predominantly inhibited melanoma cell proliferation, invasion, and tumor growth, with minimal contribution from its protein phosphatase and scaffold functions. A drug screen underscored the exquisite dependence of PTEN-deficient melanoma cells on the AKT/mTOR pathway. Furthermore, activation of AKT alone was sufficient to counteract several aspects of PTEN-mediated melanoma suppression, particularly invasion and the growth of allograft tumors. Phosphoproteomics analysis of the lipid phosphatase activity of PTEN validated its potent inhibition of AKT and many of its known targets, while also identifying the AP-1 transcription factor FRA1 as a downstream effector. The restoration of PTEN dampened FRA1 translation by inhibiting AKT/mTOR signaling, and FRA1 overexpression negated aspects of PTEN-mediated melanoma suppression akin to AKT. This study supports AKT as the key mediator of PTEN inactivation in melanoma and identifies an AKT/mTOR/FRA1 axis as a driver of melanomagenesis., Significance: PTEN suppresses melanoma predominantly through its lipid phosphatase function, which when lost, elevates FRA1 levels through AKT/mTOR signaling to promote several aspects of melanomagenesis., (©2024 American Association for Cancer Research.)

This paper presents a novel quasi-zero stiffness vibration sensing and energy harvesting integration system for absolute displacement measurements based on a buckled piezoelectric Euler beam (BPEB) with quasi-zero stiffness (QZS) characteristics. On one hand, BPEB provides negative stiffness to the system, thus creating a vibration-free point within the system and transforming the absolute displacement measurement problem into a relative motion sensing problem. On the other hand, during the measurement process, the BPEB collects the vibration energy from the system, which can provide electrical energy for low-power relative motion sensing devices and remarkably suppress the frequency range of the jump phenomenon, thereby further expanding the frequency domain measurement range of the sensing system. The research results have shown that this system can measure the absolute motion signal of the tested object in low-frequency vibration with small excitation. By adjusting parameters such as the force-electric coupling coefficient and damping ratio, the measurement accuracy of the sensing system can be improved. Furthermore, the system can convert the mechanical energy of vibrations into electrical energy to power the surrounding low-power sensors or provide partial power. This could potentially achieve self-powering integrated quasi-zero stiffness vibration sensing, offering another approach and possibility for the automation development in wireless sensing systems and the Internet of Things field.

Background: Scores for predicting the long-term mortality of severe pneumonia are lacking. The purpose of this study is to use machine learning methods to develop new pneumonia scores to predict the 1-year mortality and hospital mortality of pneumonia patients on admission to the intensive care unit (ICU)., Methods: The study population was screened from the MIMIC-IV and eICU databases. The main outcomes evaluated were 1-year mortality and hospital mortality in the MIMIC-IV database and hospital mortality in the eICU database. From the full data set, we separated patients diagnosed with community-acquired pneumonia (CAP) and ventilator-associated pneumonia (VAP) for subgroup analysis. We used common shallow machine learning algorithms, including logistic regression, decision tree, random forest, multilayer perceptron and XGBoost., Results: The full data set of the MIMIC-IV database contained 4697 patients, while that of the eICU database contained 13760 patients. We defined a new pneumonia score, the "Integrated CCI-APS", using a multivariate logistic regression model including six variables: metastatic solid tumor, Charlson Comorbidity Index, readmission, congestive heart failure, age, and Acute Physiology Score III. The area under the curve (AUC) and accuracy of the integrated CCI-APS were assessed in three data sets (full, CAP, and VAP) using both the test set derived from the MIMIC-IV database and the external validation set derived from the eICU database. The AUC value ranges in predicting 1-year and hospital mortality were 0.784-0.797 and 0.691-0.780, respectively, and the corresponding accuracy ranges were 0.723-0.725 and 0.641-0.718, respectively., Conclusions: The main contribution of this study was a benchmark for using machine learning models to build pneumonia scores. Based on the idea of integrated learning, we propose a new integrated CCI-APS score for severe pneumonia. In the prediction of 1-year mortality and hospital mortality, our new pneumonia score outperformed the existing score., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

In the last 50 years, over 150 various chemical modifications on RNA molecules, including mRNAs, rRNAs, tRNAs, and other noncoding RNAs (ncRNAs), have been identified and characterized. These RNA modifications regulate RNA biogenesis and biological functions and are widely involved in various physiological processes and diseases, including cancer. In recent decades, broad interest has arisen in the epigenetic modification of ncRNAs due to the increased knowledge of the critical roles of ncRNAs in cancer. In this review, we summarize the various modifications of ncRNAs and highlight their roles in cancer initiation and progression. In particular, we discuss the potential of RNA modifications as novel biomarkers and therapeutic targets in cancer., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

The head and neck region is one of the anatomic sites commonly afflicted by cancer, with ~1.5 million new diagnoses reported worldwide in 2020 alone. Remarkable progress has been made in understanding the underlying disease mechanisms, personalizing care based on each tumor's individual molecular characteristics, and even therapeutically exploiting the inherent vulnerabilities of these neoplasms. In this regard, genetically engineered mouse models (GEMMs) have played an instrumental role. While progress in the development of GEMMs has been slower than in other major cancer types, several GEMMs are now available that recapitulate most of the heterogeneous characteristics of head and neck cancers such as the tumor microenvironment. Different approaches have been employed in GEMM development and implementation, though each can generally recapitulate only certain disease aspects. As a result, appropriate model selection is essential for addressing specific research questions. In this review, we present an overview of all currently available head and neck cancer GEMMs, encompassing models for head and neck squamous cell carcinoma, nasopharyngeal carcinoma, and salivary and thyroid gland carcinomas., (© 2023. The Author(s).)

Objective: The purpose of this study was to characterize real-world studies (RWSs) registered at ClinicalTrials.gov to help investigators better conduct relevant research in clinical practice., Methods: A retrospective analysis of 944 studies was performed on February 28, 2023., Results: A total of 944 studies were included. The included studies involved a total of 48 countries. China was the leading country in terms of the total number of registered studies (37.9%, 358), followed by the United States (19.7%, 186). Regarding intervention type, 42.4% (400) of the studies involved drugs, and only 9.1% (86) of the studies involved devices. Only 8.5% (80) of the studies mentioned both the detailed study design type and data source in the "Brief Summary". A total of 49.4% (466) of studies had a sample size of 500 participants and above. Overall, 63% (595) of the studies were single-center studies. A total of 213 conditions were covered in the included studies. One-third of the studies (32.7%, 309) involved neoplasms (or tumors). China and the United States were very different regarding the study of different conditions., Conclusion: Although the pandemic has provided new opportunities for RWSs, the rigor of scientific research still needs to be emphasized. Special attention needs to be given to the correct and comprehensive description of the study design in the Brief Summary of registered studies, thereby promoting communication and understanding. In addition, deficiencies in ClinicalTrials.gov registration data remain prominent., Competing Interests: All authors declared no potential conflicts of interest in this work., (© 2023 Li et al.)

Halogenated arylamines are important intermediates for the synthesis of dyes, pesticides, herbicides, and other chemicals. One important way to prepare halogenated arylamines is catalytic hydrogenation of halogenated nitroarenes. Ni-based catalysts have been used in the hydrogenation of halogenated nitroarenes but suffer from low activity and dehalogenation side reaction. In this paper, Ni-CeO 2 /SiO 2 heterojunction catalyst with a "raisin-bun" structure was prepared by reverse microemulsion. A built-in electric field and more oxygen vacancies were formed due to electron transfer from Ni to CeO 2 as a result of their work function difference. The built-in electric field leads to the heterolytic cleavage of H 2 , thereby improving the hydrogenation activity. Oxygen vacancies preferentially adsorb and activate nitro groups, inhibiting the dehalogenation side reaction. Through the cooperation of built-in electric field and oxygen vacancy, synchronous enhancement of the activity and selectivity is obtained successfully. This finding provides a new view for the design of non-noble metal-based catalysts with high activity and selectivity.

The process of oncogene-induced senescence (OIS) and the conversion between OIS and malignant transformation during carcinogenesis is poorly understood. Here, we show that following overactivation of oncogene Ras in lung epithelial cells, high-level transforming growth factor β1 (TGF-β1)-activated SMAD3, but not SMAD2 or SMAD4, plays a determinant role in inducing cellular senescence independent of the p53/p16/p15 senescence pathways. Importantly, SMAD3 binds a potential tumor suppressor ATOH8 to form a transcriptional complex that directly represses a series of cell cycle-promoting genes and consequently causes senescence in lung epithelial cells. Interestingly, the prosenescent SMAD3 converts to being oncogenic and essentially facilitates oncogenic Ras-driven malignant transformation. Furthermore, depleting Atoh8 rapidly accelerates oncogenic Ras-driven lung tumorigenesis, and lung cancers driven by mutant Ras and Atoh8 loss, but not by mutant Ras only, are sensitive to treatment of a specific SMAD3 inhibitor. Moreover, hypermethylation of the ATOH8 gene can be found in approximately 12% of clinical lung cancer cases. Together, our findings demonstrate not only epithelial cellular senescence directed by a potential tumor suppressor-controlled transcriptional program but also an important interplay between the prosenescent and transforming effects of TGF-β/SMAD3, potentially laying a foundation for developing early detection and anticancer strategies.

Neuroinflammation is the inflammatory responses that are involved in the pathogenesis of most neurological disorders. Glutaminase (GLS) is the enzyme that catalyzes the hydrolysis of glutamine to produce glutamate. Besides its well-known role in cellular metabolism and excitatory neurotransmission, GLS has recently been increasingly noticed to be up-regulated in activated microglia under pathological conditions. Furthermore, GLS overexpression induces microglial activation, extracellular vesicle secretion, and neuroinflammatory microenvironment formation, which, are compromised by GLS inhibitors in vitro and in vivo. These results indicate that GLS has more complicated implications in brain disease etiology than what are previously known. In this review, we introduce GLS isoforms, expression patterns in the body and the brain, and expression/activities regulation. Next, we discuss the metabolic and neurotransmission functions of GLS. Afterwards, we summarize recent findings of GLS-mediated microglial activation and pro-inflammatory extracellular vesicle secretion, which, in turns, induces neuroinflammation. Lastly, we provide a comprehensive discussion for the involvement of microglial GLS in the pathogenesis of various neurological disorders, indicating microglial GLS as a promising target to treat these diseases., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Pseudogenes may function as competitive endogenous RNAs (ceRNAs), where they regulate the expression of genes by sequestering shared miRNAs. ceRNAs are becoming more extensively identified and studied, and demonstrating the dependence of their effects on miRNA sequestration is critical to establish them as ceRNAs. Here, we outline an experimental approach to assess the miRNA dependency of a candidate pseudogene ceRNA.

It is well acknowledged that immune system is deeply involved in cancer initiation and progression, and can exert both pro-tumorigenic and anti-tumorigenic effects, depending on specific microenvironment. With the better understanding of cancer-associated immune cells, especially T cells, immunotherapy was developed and applied in multiple cancers and exhibits remarkable efficacy. However, currently only a subset of patients have responses to immunotherapy, suggesting that a boarder view of cancer immunity is required. Non-coding RNAs (ncRNAs), mainly including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), are identified as critical regulators in both cancer cells and immune cells, thus show great potential to serve as new therapeutic targets to improve the response of immunotherapy. In this review, we summarize the functions and regulatory mechanisms of ncRNAs in cancer immunity, and highlight the potential of ncRNAs as novel targets for immunotherapy.

Post-stroke induction of alpha-synuclein (AS), a neuronal protein implicated in the pathogenesis of Parkinson's disease (PD), has been demonstrated to induce secondary brain damage after cerebral ischemia. Therefore, understanding the expression and pathogenic modifications of AS is clinically meaningful for evaluating the prognosis of stroke. Here, 54 patients with acute ischemic stroke (AIS) and 55 controls were enrolled. Different forms of AS in red blood cells (RBCs), including hemoglobin-bound AS (Hb-AS), oligomeric AS (O-AS), and serine 129-phosphorylated AS (pS-AS), were measured using ELISA methods. Compared with controls, significantly increased levels of Hb-AS, O-AS, and pS-AS were observed in AIS patients. The levels of O-AS and pS-AS were both positively correlated with that of Hb-AS. However, no correlation was observed between O-AS and pS-AS. The levels of all three forms of AS were associated with increased risk of AIS diagnosis. Receiver operating characteristic (ROC) curves revealed that the three forms of AS yielded a moderate discriminative power (AUC ranging from 0.67 to 0.71 in discriminating AIS patients from controls, with varying sensitivity (0.41~0.61), specificity (0.78~0.90), PPV (0.73~0.81), and NPV (0.61~0.68)). These findings suggest that RBC AS can be a potential biomarker for evaluating AS changes in the brain of AIS patients., Competing Interests: None., (IJCEP Copyright © 2019.)

Oral carcinoma (OC) is the major cancer type in the head and neck region; however, the molecular mechanisms of its pathogenesis and progression remain poorly understood. In recent years, the long noncoding RNAs (lncRNAs) have been uncovered as critical regulators in the development and progression of multiple human cancers, but most of the lncRNAs expression patterns, clinical relevance, and biological functions in OC are still unclear. To better understand the significance of lncRNAs in OC carcinogenesis, we analyzed the expression levels of lncRNAs between OC and healthy oral mucosa using The Cancer Genome Atlas Cancer Genome RNA sequencing data and another three independent microarray datasets from Gene Expression Omnibus. As a result, we found that thousands of lncRNAs expression are dysregulated in OC, and further somatic copy number variation analyses showed that some of these lncRNAs alterations are associated with copy number amplification or loss in OC. Moreover, lots of lncRNAs expression levels are associated with OC patients' overall survival and recurrence-free survival; for example, higher CASC9, LINC01232, and MIR4435-1HG expression levels are related to shorter overall survival and recurrence-free survival in OC patients. Finally, the potential function of two lncRNAs (CASC9 and LINC00152) that were upregulated in OC tissues and associated with patients' survival time was verified by loss-of-function assays in OC cells. Our findings indicate that these altered lncRNAs might play important roles in the development of OC, and our data can provide a valuable list of lncRNAs candidates for further investigation of their function and mechanisms in OC.

The contribution of autophagy to cancer development remains controversial, largely owing to the fact that autophagy can be tumour suppressive or oncogenic in different biological contexts. Here, we show that in non-small-cell lung cancer (NSCLC), casein kinase 1 alpha 1 (CK1α) suppresses tumour growth by functioning as an autophagy inducer to activate an autophagy-regulating, tumour-suppressive PTEN/AKT/FOXO3a/Atg7 axis. Specifically, CK1α bound the C-terminal tail of PTEN and enhanced both PTEN stability and activity by competitively antagonizing NEDD4-1-induced PTEN polyubiquitination and abrogating PTEN phosphorylation, thereby inhibiting AKT activity and activating FOXO3a-induced transcription of Atg7. Notably, blocking CK1α-induced Atg7-dependent autophagy cooperates with oncogenic HRas V12 to initiate tumorigenesis of lung epithelial cells. An association of a CK1α-modulated autophagic program with the anti-neoplastic activities of the CK1α/PTEN/FOXO3a/Atg7 axis was demonstrated in xenografted tumour models and human NSCLC specimens. This provides insights into the biological and potentially clinical significance of autophagy in NSCLC.

Drug loading into γ-cyclodextrin-metal organic frameworks (γ-CD-MOFs) using the impregnation approach is a laborious process. In this study, a γ-CD-MOF construct (2-5μm particle diameter) was used as the stationary phase under HPLC conditions with the aim to correlate retention properties and drug loading capability of the CD-based structure. Ketoprofen, fenbufen and diazepam were chosen as model drugs with m-xylene as a control analyte to investigate the correlation of drug loading and their chromatographic behaviour in the γ-CD-MOF column. Furthermore, γ-CD itself was also prepared as the stationary phase by coupling with silica in the column to illustrate the enhanced interaction between drugs and γ-CD-MOF as a reference. The retention and loading efficiency of the drugs were determined with different ratios of hexane and ethanol (10:90, 20:80, 50:50, 80:20, 90:10, v/v) at temperatures of 20, 25, 30 and 37°C. With the increment in hexane content, the loading efficiency of ketoprofen and fenbufen increased from 2.39±0.06% to 4.38±0.04% and from 5.82±0.94% to 6.37±0.29%, respectively. The retention time and loading efficiency of ketoprofen and diazepam were the lowest at 30°C while those of fenbufen had the different tendency. The excellent relation between the retention and loading efficiency onto γ-CD-MOF could be clearly observed through mobile phase and temperature investigation. In conclusion, a highly efficient chromatographic method has been established to evaluate the drug loading capability of γ-CD-MOF., (Copyright © 2017 Elsevier B.V. All rights reserved.)