Anticancer potential of grifolin in lung cancer treatment through PI3K/AKT pathway inhibition.

Objective: Grifolin is a natural secondary metabolite isolated from edible fruiting bodies of the mushroom Albatrellus confluens. Grifolin has antitumor activities in several types of cancer. We aimed to determine the effects of grifolin on lung cancer. Methods: We determined the proliferation, migration, invasion, and apoptosis of lung cancer cells using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, Ethynyl deoxyuridine, colony formation, wound scratch, transwell, flow cytometry, and xenograft mouse assays. Molecular docking evaluated the binding relation between grifolin and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA). The levels of PIK3CA, AKT, and p-AKT were measured by western blot. Results: Grifolin (10, 20, or 40 µM) inhibited the proliferation, migration, and invasion of lung cancer cells, and induced cell cycle arrest and apoptosis. Grifolin also decreased CDK4, CDK6, and CyclinD1 expression and significantly decreased PIK3CA and p-AKT expression in lung cancer cells. These anticancer effects were abolished by 740Y-P. Conclusions: Grifolin regulates the PI3K/AKT pathway, thus inhibiting lung cancer progression.

Codelivery of Doxorubicin and p53 Gene by ß-Cyclodextrin-Based Supramolecular Nanoparticles Formed via Host-Guest Complexation and Electrostatic Interaction.

We developed a supramolecular system for codelivery of doxorubicin (Dox) and p53 gene based on a ß-CD-containing star-shaped cationic polymer. First, a star-shaped cationic polymer consisting of a ß-CD core and 3 arms of oligoethylenimine (OEI), named CD-OEI, was used to form a supramolecular inclusion complex with hydrophobic Dox. The CD-OEI/Dox complex was subsequently used to condense plasmid DNA via electrostatic interactions to form CD-OEI/Dox/DNA polyplex nanoparticles with positive surface charges that enhanced the cellular uptake of both Dox and DNA. This supramolecular drug and gene codelivery system showed high gene transfection efficiency and effective protein expression in cancer cells. The codelivery of Dox and DNA encoding the p53 gene resulted in reduced cell viability and enhanced antitumor effects at low Dox concentrations. With its enhanced cellular uptake and anticancer efficacy, the system holds promise as a delivery carrier for potential combination cancer therapies.

A supramolecular colloidal system based on folate-conjugated ß-cyclodextrin polymer and indocyanine green for enhanced tumor-targeted cell imaging in 2D culture and 3D tumor spheroids.

Indocyanine green (ICG) is an FDA-approved medical diagnostic agent that is widely used as a near-infrared (NIR) fluorescent imaging molecular probe. However, ICG tends to aggregate to form dimers or H-aggregates in water and lacks physical and optical stability, which greatly decreases its absorbance and fluorescence intensity in various applications. Additionally, ICG has no tissue- or tumor-targeting properties, and its structure is not easy to modify, which has further limited its application in cancer diagnosis. In this study, we addressed these challenges by developing a supramolecular colloidal carrier system that targets tumor cells. To this end, we synthesized a water-soluble ß-cyclodextrin (ß-CD) polymer conjugated with folate (FA), denoted PCD-FA, which is capable of forming inclusion complexes with ICG in water through host-guest interactions between the ß-CD moieties and ICG molecules. The inclusion complexes formed by PCD-FA and ICG, called ICG@PCD-FA, dispersed stably in solution as colloidal nanoparticles, greatly improving the physical and optical properties of ICG by preventing ICG dimer formation, where ICG appeared as monomers and even J-aggregates. This resulted in stronger and more stable absorption at a longer wavelength of 900 nm, which may allow for deeper tissue penetration and imaging with reduced interference from biological tissues' autofluorescence. Moreover, ICG@PCD-FA showed a targeting effect on folate receptor-positive (FR+) tumor cells, which specifically highlighted FR+ cells via NIR endoscopic imaging. Notably, ICG@PCD-FA further improved permeation and accumulation in FR+ 3D tumor spheroids. Therefore, this ICG@PCD-FA supramolecular colloidal system may have a great potential for use in tumor NIR imaging and diagnostic applications.

Exploring the Low-Dose Limit for Focal Hepatic Lesion Detection with a Deep Learning-Based CT Reconstruction Algorithm: A Simulation Study on Patient Images.

This study aims to investigate the maximum achievable dose reduction for applying a new deep learning-based reconstruction algorithm, namely the artificial intelligence iterative reconstruction (AIIR), in computed tomography (CT) for hepatic lesion detection. A total of 40 patients with 98 clinically confirmed hepatic lesions were retrospectively included. The mean volume CT dose index was 13.66 ± 1.73 mGy in routine-dose portal venous CT examinations, where the images were originally obtained with hybrid iterative reconstruction (HIR). Low-dose simulations were performed in projection domain for 40%-, 20%-, and 10%-dose levels, followed by reconstruction using both HIR and AIIR. Two radiologists were asked to detect hepatic lesion on each set of low-dose image in separate sessions. Qualitative metrics including lesion conspicuity, diagnostic confidence, and overall image quality were evaluated using a 5-point scale. The contrast-to-noise ratio (CNR) for lesion was also calculated for quantitative assessment. The lesion CNR on AIIR at reduced doses were significantly higher than that on routine-dose HIR (all p < 0.05). Lower qualitative image quality was observed as the radiation dose reduced, while there were no significant differences between 40%-dose AIIR and routine-dose HIR images. The lesion detection rate was 100%, 98% (96/98), and 73.5% (72/98) on 40%-, 20%-, and 10%-dose AIIR, respectively, whereas it was 98% (96/98), 73.5% (72/98), and 40% (39/98) on the corresponding low-dose HIR, respectively. AIIR outperformed HIR in simulated low-dose CT examinations of the liver. The use of AIIR allows up to 60% dose reduction for lesion detection while maintaining comparable image quality to routine-dose HIR.

Protein-assisted synthesis of chitosan-coated minicells enhance dendritic cell recruitment for therapeutic immunomodulation within pulmonary tumors.

The efficacy of cancer therapies is significantly compromised by the immunosuppressive tumor milieu. Herein, we introduce a previously unidentified therapeutic strategy that harnesses the synergistic potential of chitosan-coated bacterial vesicles and a targeted chemotherapeutic agent to activate dendritic cells, thereby reshaping the immunosuppressive milieu for enhanced cancer therapy. Our study focuses on the protein-mediated modification of bacterium-derived minicells with chitosan molecules, facilitating the precise delivery of Doxorubicin to tumor sites guided by folate-mediated homing cues. These engineered minicells demonstrate remarkable specificity in targeting lung carcinomas, triggering immunogenic cell death and releasing tumor antigens and damage-associated molecular patterns, including calreticulin and high mobility group box 1. Additionally, the chitosan coating, coupled with bacterial DNA from the minicells, initiates the generation of reactive oxygen species and mitochondrial DNA release. These orchestrated events culminate in dendritic cell maturation via activation of the stimulator of interferon genes signaling pathway, resulting in the recruitment of CD4+ and CD8+ cytotoxic T cells and the secretion of interferon-ß, interferon-γ, and interleukin-12. Consequently, this integrated approach disrupts the immunosuppressive tumor microenvironment, impeding tumor progression. By leveraging bacterial vesicles as potent dendritic cell activators, our strategy presents a promising paradigm for synergistic cancer treatment, seamlessly integrating chemotherapy and immunotherapy.

Impacts of biochar aging on its interactions with As(III) and the combined cytotoxicity.

Despite the extensive use of biochar (BC) in soil and aqueous media for pollutant immobilization, the environmental behaviors and health risks of aged BC with multiple pollutants, especially with metal ions possessing various valence states, remain unexplored. Here, we prepared fresh banana peel BC (BP-BC) and aged BP-BCs by acidification (ABP-BC) and oxidation (OBP-BC). ABP-BC was then chosen to explore its environmental behaviors (i.e., adsorption, desorption, and arsenic valence transfer) towards As(III)-Cu(II) and the combined cytotoxicity of BCs with As(III)-Cu(II) was investigated in Human Gastric epithelium cells (GES-1). Our results demonstrate that the aging process notably alters the physicochemical properties of BP-BC, including surface morphology, elemental composition, and surface functional groups, which are key factors affecting the long-term environmental behaviors of BC with As(III)/Cu(II). Specifically, the aging process significantly enhanced the adsorption of As(III) on BC but reduced the adsorption of Cu(II). Although the oxidation of As(III) to As(V) did not change much, the aging process improved the stability of ABP-BC-metal ion complexes, alleviating the release of As(III) in acidic solution. Consequently, the combined cytotoxicity induced by ABP-BC-As(III)-Cu(II) was reduced compared to BP-BC-As(III)-Cu(II). The study highlights the critical roles of the aging process in regulating the As(III) adsorption/desorption dynamics on BCs and their combined cytotoxicity in the presence of multiple metal ions.

Application of deep learning image reconstruction-high algorithm in one-stop coronary and carotid-cerebrovascular CT angiography with low radiation and contrast doses.

Background: For patients with suspected simultaneous coronary and cerebrovascular atherosclerosis, conventional single-site computed tomography angiography (CTA) for both sites can result in nonnegligible radiation and contrast agent dose. The purpose of this study was to validate the feasibility of one-stop coronary and carotid-cerebrovascular CTA (C&CC-CTA) with a "double-low" (low radiation and contrast) dose protocol reconstructed with deep learning image reconstruction with high setting (DLIR-H) algorithm. Methods: From February 2018 to January 2019, 60 patients referred to C&CC-CTA simultaneously in West China Hospital were recruited in this prospective cohort study. By random assignment, patients were divided into two groups: double-low dose group (n=30) used 80 kVp and 24 mgI/kg/s contrast dose with images reconstructed using DLIR-H; and routine-dose group (n=30) used 100 kVp and 32 mgI/kg/s contrast dose with images reconstructed using 50% adaptive statistical iterative reconstruction-V (ASIR-V50%). Radiation and contrast doses, subjective image quality score, CT attenuation values, noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were measured and compared between the groups. Results: The DLIR-H group used 30% less contrast dose (35.80±4.85 vs. 51.13±6.91 mL) and 48% less overall radiation dose (1.00±0.09 vs. 1.91±0.42 mSv) than the ASIR-V50% group (both P<0.001). There was no statistically significant difference on subjective quality score between the two groups (C-CTA: 4.38±0.67 vs. 4.17±0.81, P=0.337 and CC-CTA: 4.18±0.87 vs. 4.08±0.79, P=0.604). For coronary CTA, lower background noise (18.93±1.43 vs. 22.86±3.75 HU) was reached in DLIR-H group, and SNR and CNR at all assessed branches were significantly increased compared to ASIR-V50% group (all P<0.05), except SNR of left anterior descending (P>0.05). For carotid-cerebrovascular CTA, DLIR-H group was comparable in background noise (19.25±1.42 vs. 20.23±2.40 HU), SNR and CNR at all assessed branches with ASIR-V50% group (all P>0.05). Conclusions: The "double-low" dose one-stop C&CC-CTA with DLIR-H obtained higher image quality compared with the routine-dose protocol with ASIR-V50% while achieving 48% and 30% reduction in radiation and contrast dose, respectively.

Soluble E-cadherin participates in BLM-induced pulmonary fibrosis by promoting EMT and lung fibroblast migration.

Soluble E-cadherin (sE-cad) is an 80 kDa fragment derived from E-cadherin that is shed from the cell surface through proteolytic cleavage and is a biomarker in various cancers that promotes invasion and migration. Alveolar epithelial destruction, aberrant lung fibroblast migration and inflammation contribute to pulmonary fibrosis. Here, we hypothesized that E-cadherin plays an important role in lung fibrosis. In this study, we found that E-cadherin was markedly increased in the bronchoalveolar lavage fluid (BALF) and serum of mice with pulmonary fibrosis and that blocking sE-cad with HECD-1, a neutralizing antibody targeting the ectodomain of E-cadherin, effectively inhibited myofibroblast accumulation and collagen deposition in the lungs after bleomycin (BLM) exposure. Moreover, transforming growth factor-ß (TGF-ß1) induced the shedding of sE-cad from A549 cells, and treatment with HECD-1 inhibited epithelial-mesenchymal transition (EMT) stimulated by TGF-ß1. Fc-E-cadherin (Fc-Ecad), which is an exogenous form of sE-cad, robustly promoted lung fibroblast migration. E-cadherin participates in bleomycin (BLM)-induced lung fibrosis by promoting EMT in the alveolar epithelium and fibroblast activation. E-cadherin may be a novel therapeutic target for lung fibrosis.

A novel splicing mutation identified in a DMD patient: a case report.

Background: Duchenne muscular dystrophy (DMD, ORPHA:98896) is a lethal X-linked recessive disease that manifests as progressive muscular weakness and wasting. Mutations in the dystrophy gene (DMD) are the main cause of Duchenne muscular dystrophy. Case presentation: This study aims to determine novel mutations of DMD and help preimplantation genetic diagnosis (PGD) for family planning. Here present a 4-year-old Chinses boy with DMD, whole-exome sequencing (WES) was performed to identify the molecular basis of the disease. It was confirmed that the boy carried a novel hemizygous mutation of NC_000023.11(NM_004006.3): c.5912_5922 + 19delinsATGTATG in DMD which inherited from his mother. This led to the aberrant splicing of DMD which demonstrated by a minigene splicing assay and further resulted in the impairment of the dystrophy protein. Conclusions: Our study discovered a novel splicing mutation of DMD in a DMD patient, which expands the variant spectrum of this gene and provide precise genetic diagnosis of DMD for timely therapy. Meanwhile, this finding will supply valuable information for preimplantation genetic diagnosis.

Rationally designed multifunctional nanoparticles as GSH-responsive anticancer drug delivery systems based on host-guest polymers derived from dextran and ß-cyclodextrin.

Tumor proliferation and metastasis rely on energy provided by mitochondria. The hexokinase inhibitor lonidamine (LND) could suppress the activities in mitochondria, being a potential antitumor drug. However, limited water-solubility of LND may hinder its biomedical applications. Besides, the cancer-killing effect of LND is compromised by the high level of glutathione (GSH) in cancer cells. Therefore, it is urgent to find a proper method to simultaneously deliver LND and deplete GSH as well as monitor GSH level in cancer cells. Herein, a host polymer ß-cyclodextrin-polyethylenimine (ß-CD-PEI) and a guest polymer dextran-5-dithio-(2-nitrobenzoic acid) (Dextran-SS-TNB) were synthesized and allowed to form LND-loaded GSH-responsive nanoparticles through host-guest inclusion complexation between ß-CD and TNB as host and guest molecular moieties, respectively, which functioned as a system for simultaneous delivery of LND and -SS-TNB species into cancer cells. As a result, the delivery system could deplete GSH and elevate reactive oxygen species (ROS) level in cancer cells, further induce LND-based mitochondrial dysfunction and ROS-based immunogenic cell death (ICD), leading to a synergistic and efficient anticancer effect. In addition, -SS-TNB reacted with GSH to release TNB2-, which could be a probe with visible light absorption at 410 nm for monitoring the GSH level in the cells.

Biomass-based single- and double-network hydrogels derived from cellulose microfiber and chitosan for potential application as plant growing substrate.

A series of hydrogels were synthesized from renewable and low-cost micro-sized cellulose fiber. The single-network hydrogel was composed of cellulose fiber and a small amount of another polysaccharide, chitosan, which 'glued' individual cellulose fiber pieces together through Schiff-base bonding. The double-network hydrogel was constructed by adding a secondary network, the covalently crosslinked polyacrylamide, into the single-network hydrogel, which was synthesized by conducting Schiff-base reaction and free radical polymerization at the same time in a facile one-pot process. In both single- and double-network hydrogels, cellulose fiber constituted the dominant component. Both types of hydrogels exhibited good swelling properties. The double-network hydrogel showed much improved stability against soaking in water and higher salt tolerance. Germination experiment with choy sum seeds sowed on hydrogel surface showed that the seeds were able to germinate and further develop roots, shoots, and true leaves, demonstrating the potential of the biomass-derived hydrogels for soilless plant growing applications.

First report of Watermelon silver mottle orthotospovirus infecting Siraitia grosvenorii in China.

Siraitia grosvenorii, known as "Luohanguo or monk fruit", is a perennial vine belonging to the family Cucurbitaceae. It is cultivated for its fruits, which are used as a Chinese traditional medicine to treat throat, lung and intestine ailments, or as raw material to extract sweet cucurbitane-glycosides as sugar substitute sweeteners (Chen et al., 2007). The production of S. grosvenorii is limited by viral diseases especially cucumber green mottle mosaic virus (CGMMV), papaya ringspot virus (PRSV), watermelon mosaic virus, and zucchini yellow mosaic virus (Liao et al., 2005; Xie et al., 2020). In 2022, virus-like disease consisting of leaf mottling, crinkling, and ringspot was observed on S. grosvenorii plants grown in an insect-proof greenhouse in Guilin City, Guangxi Province, China, with an incidence rate of ~17%. High-throughput sequencing (HTS) was applied to identify potential viruses in the diseased plants. Briefly, total RNA was extracted from a pool of 28 leaf samples (with or without symptoms) of S. grosvenorii using Trizol reagent according to manufacturer's instructions (Invitrogen, U.S.A.). The rRNA was depleted (Epicentre Ribo-zero™ rRNA Removal Kit, Epicentre, U.S.A.), before steps of cDNA library construction (NEBNext® Ultra™ Directional RNA Library Prep Kit for Illumina®, NEB, U.S.A.), and sequencing (Hiseq 4000 platform, Illumina, U.S.A.). The subsequent bioinformatics analyses were performed according to Liu et al. (2021). HTS of the sample and raw reads processing resulted in 8.4 Gb clean data. The clean reads (150 bp) were de novo assembled into 87,414 contigs (≥200 bp), using CLC Genomics Workbench 21 (Qiagen, Germany). The contigs were annotated by local BLASTX, resulting in matches to CGMMV, PRSV, and watermelon silver mottle virus (WSMoV). Three contigs of 6,557 bp, 4,950 bp, and 3,594 bp were most identical to L (GenBank accession no. JX177647), M (MW051789), and S (KM242056) segments of WSMoV. The complete genome sequences corresponding to the contigs derived from the sample (designated as GL-1 variant of WSMoV, OQ401466-OQ401468) were obtained by reads mapping to segments of these isolates. The reads coverage was ≥99.75% in each RNA segment and the depth of the coverage was in a range of 74-285. To detect the presence of GL-1 in S. grosvenorii plants, three primer pairs D7280F/D7382R (5'-TGATAGCCTGATGAACACCA/5'-TGTCTCTAAACCTTCTACCGC, Tm = 55℃, product size 172 bp), D4512F/D4703R (5'-GCATTGAACTCGCTCACAC/5'-AGTAGACGACCCTGAAGACCT, Tm = 55℃, 192 bp), and D109F/D451R (5'-TTATGGCACAAGAGACAACAGAG/5'-GGGCGTTATGTTCAGTATATTGG, Tm = 56℃, 342 bp) were designed in the L, M, and S segments, respectively. Fresh symptomatic and asymptomatic leaf tissues (n=38) were collected from three fields and their extracted nucleic acids were individually tested with the primers designed by two-steps RT-PCR using TaKaRa RNA PCR kit Ver.3.0 (Takara, Japan). Expected amplicons were obtained in symptomatic samples (n=7) showing mottling, crinkling, and chlorosis. Other samples (n=31) with or without symptoms were negative to WSMoV infection. The amplicons were sequenced, and the sequences obtained shared >99% nt identities with the corresponding GL-1 sequences in GenBank. This is the first report of WSMoV on S. grosvenorii, which provides the basic information for virus disease management.

Versatile delivery platform for nucleic acids, negatively charged protein drugs, and genome-editing ribonucleoproteins using a multi-step transformable polyrotaxane.

Various biopharmaceuticals, such as nucleic acids, proteins, and genome-editing molecules, have been developed. Generally, carriers are prepared for each biopharmaceutical to deliver it intracellularly; thus, the applications of individual carriers are limited. Moreover, the development of carriers is laborious and expensive. Therefore, in the present study, versatile and universal delivery carriers were developed for various biopharmaceuticals using aminated polyrotaxane libraries. Step-by-step and logical screening revealed that aminated polyrotaxane, including the carbamate bond between the axile molecule and endcap, is suitable as a backbone polymer. Movable and flexible properties of the amino groups modified on polyrotaxane facilitated efficient complexation with various biopharmaceuticals, such as small interfering RNA, antisense oligonucleotides, messenger RNA, ß-galactosidase, and genome-editing ribonucleoproteins. Diethylenetriamine and cystamine modifications of polyrotaxane provided endosomal-escape abilities and drug-release properties in the cytosol, allowing higher delivery efficacies than commercially available high-standard carriers without cytotoxicity. Thus, the resulting polyrotaxane might serve as a versatile and universal delivery platform for various biopharmaceuticals.

Design, synthesis, and analgesia evaluation of novel Transient Receptor Potential Vanilloid 1 (TRPV1) agonists modified from Cannabidiol (CBD).

Pain-relief is a long-term research hotspot with huge demand in clinical treatment. The analgesics currently used have several side effects, such as being addictive and causing gastrointestinal bleeding. Therefore, new drugs and targets in analgesic field are both desirable. Transient Receptor Potential Vanilloid 1 (TRPV1) plays an essential role in pain perception and regulation, providing a new strategy for the development of antinociceptive agents. Here, a series of novel TRPV1 agonists were designed and synthesized based on Cannabidiol (CBD), a widely used pain-relieving agent with weak agonistic activity on TRPV1. According to the results of systematic in vitro and in vivo biological assays, compound 10f was finally identified as a promising TRPV1 agonist, with higher target affinity, stronger analgesic activity, and weak side effect of hyperthermia. Molecular docking simulations revealed a significant hydrogen bond interaction between 10f and Arg557, an amino acid residue key to the activity of TRPV1 protein. Taken together, compound 10f can be used as a lead compound for further optimization.

The antinociceptive activity and mechanism of action of cannabigerol.

Cannabis has been used for centuries to treat pain. The antinociceptive activity of tetrahydrocannabinol (THC) or cannabidiol (CBD) has been widely studied. However, the antinociceptive effects of other cannabis components, such as cannabichromene (CBC) and cannabigerol (CBG), have rarely been revealed. The antinociceptive mechanism of CBG is not yet clear, so we investigated the antinociceptive effect of CBG on different pain models, and explored the mechanism of action of CBG to exert antinociceptive effects. In the current study, we compared the antinociceptive effects of CBC, CBD, and CBG on the carrageenan-induced inflammatory pain model in mice, and the results showed that CBG had a better antinociceptive effects through intraplantar administration. On this basis, we further investigated the antinociceptive effect of CBG on CIA-induced arthritis pain model and nerve pain model in mice, and found that CBG also relieved on both types of pain. Then, we explored the antinociceptive mechanism of CBG, which revealed that CBG can activate TRPV1 and desensitize it to block the transmission of pain signals. In addition, CBG can further activate CB2R, but not CB1R, to stimulate the release of ß-endorphin, which greatly promotes the antinociceptive effect. Finally, the safety test results showed that CBG had no irritating effect on the rabbits' skin, and it did not induce significant biochemical and hematological changes in mice. Transdermal delivery results also indicated that CBG has certain transdermal properties. Overall, this study indicates that CBG is promising for developing a transdermal dosage for pain management.

PLVAP protein expression correlated with microbial composition, clinicopathological features, and prognosis of patients with stomach adenocarcinoma.

PURPOSE: Plasmalemma vesicle-associated protein (PLVAP) is involved in many immune­related signals; however, its role in stomach adenocarcinoma (STAD) remains to be elucidated. This study investigated PLVAP expression in tumor tissues and defined the value in STAD patients. METHODS: A total of 96 patient paraffin-embedded STAD specimens and 30 paraffin-embedded adjacent non-tumor specimens from the Ninth Hospital of Xi'an were consecutively recruited in analyses. All RNA­sequence data were available from the Cancer Genome Atlas database (TCGA). PLVAP protein expression was detected using immunohistochemistry. Microbial community analysis was performed by 16S rRNA gene sequencing using Illumina MiSeq. PLVAP mRNA expression was explored with the Tumor Immune Estimation Resource (TIMER), GEPIA, and UALCAN databases. The effect of PLVAP mRNA on prognosis was analyzed via GEPIA, and Kaplan-Meier plotter database. GeneMANIA and STRING databases were used to predict gene/protein interactions and functions. The relationships between PLVAP mRNA expression and tumor-infiltrated immune cells were analyzed via the TIMER and GEPIA databases. RESULTS: Significantly elevated transcriptional and proteomic PLVAP expressions were found in STAD samples. Increased PLVAP protein and mRNA expression were significantly associated with advanced clinicopathological parameters and correlated with shorter disease-free survival (DFS) and overall survival (OS) in TCGA (P < 0.001). The microbiota in the PLVAP-rich (3+) group was significantly different from that in the PLVAP-poor (1+) group (P < 0.05). The results from TIMER showed that high PLVAP mRNA expression had significant positive correlations with CD4 + T cell (r = 0.42, P < 0.001). CONCLUSION: PLVAP is a potential biomarker to predict the prognosis of patients with STAD, and the high level of PLVAP protein expression was closely related to bacteria. The relative abundance of Fusobacteriia was positvely associated with the level of PLVAP. In conclusion, positive staining for PLVAP was useful for predicting the poor prognosis of STAD with Fusobacteriia infection.

Challenges of conducting of online educational programs for family caregivers of people with dementia living at home: An integrative review.

Objectives: This integrative review aimed to understand the challenges of conducting online educational programs for family caregivers of people with dementia by focusing on the components and design of them. Methods: Following Whittemore & Knafl's five-step method, seven databases were systematically searched. The Mixed Methods Appraisal Tool was used to evaluate the quality of the studies. Results: Of the 25,256 articles identified, 49 studies were included. Limitations in components (including useless or repetitive information, incomplete access to dementia-related information, the impact of components related to culture or ethnicity or gender) and in the format of delivered information (including less interaction, time schedule limitations and preference for traditional forms of delivery of information) make it more challenging to conduct online educational programs. Additionally, implementation constraints such as technical problems, poor computer literacy, and fidelity assessment are challenges that cannot be ignored. Conclusions: Insight into the challenges of online educational programs for family caregivers of people with dementia can help guide researchers in constructing the optimal online educational program. Incorporating cultural specificity, considering structured construction strategies, optimizing interaction design, and increasing fidelity assessment may contribute to the conduct of online educational programs.

Association between career adaptability and turnover intention among nursing assistants: the mediating role of psychological capital.

BACKGROUND: High turnover intention of nursing assistants was detrimental to the sustainability of long-term care. Career adaptability is an important determinant in reducing turnover intention, but little research has explored the mechanism from the perspective of psychological capital. The aim of this study was to analyze the association between career adaptability and turnover intention and to examine the mediating role of psychological capital between career adaptability and turnover intention among nursing assistants in mainland China. METHODS: A cross-sectional online study was conducted among 276 nursing assistants from eight nursing homes in Nanjing, China. The participants' career adaptability, psychological capital, and turnover intention were obtained. SPSS 26.0 and Amos 24.0 software were employed for statistical analysis. RESULTS: Career adaptability was positively related to psychological capital and negatively linked to turnover intention (P < 0.01). Psychological capital played a fully mediating role (ß = -0.085, P < 0.05) in the relationship between career adaptability and turnover intention, and the largest indirect effect was generated through the curiosity dimension. CONCLUSIONS: The management of long-term care facilities should focus on assessing the level of career adaptability of nursing assistants. The overall improvement of career adaptability and psychological capital is conducive in reducing turnover intention. Targeted interventions are recommended to improve career adaptability and reduce turnover intentions by increasing career curiosity. Online career adaptability programs can be developed for nursing assistant students to improve their psychological capital and facilitate career transitions.

Reducing both radiation and contrast doses for overweight patients in coronary CT angiography with 80-kVp and deep learning image reconstruction.

PURPOSE: To investigate the use of an 80-kVp tube voltage combined with a deep learning image reconstruction (DLIR) algorithm in coronary CT angiography (CCTA) for overweight patients to reduce radiation and contrast doses in comparison with the 120-kVp protocol and adaptive statistical iterative reconstruction (ASIR-V). METHODS: One hundred consecutive CCTA patients were prospectively enrolled and randomly divided into a low-dose group (n = 50) with 80-kVp, smart mA for noise index (NI) of 36 HU, contrast dose rate of 18 mgI/kg/s and DLIR and 60 % ASIR-V and a standard-dose group (n = 50) with 120-kVp, smart mA for NI of 25 HU, contrast dose rate of 32 mgI/kg/s and 60 % ASIR-V. The radiation and contrast dose, subjective image quality score, attenuation values, noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were compared. RESULTS: The low-dose group achieved a significant reduction in the effective radiation dose (1.01 ± 0.45 mSv vs 1.85 ± 0.40 mSv, P < 0.001) and contrast dose (33.69 ± 3.87 mL vs 59.11 ± 5.60 mL, P < 0.001) compared to the standard-dose group. The low-dose group with DLIR presented similar enhancement but lower noise, higher SNR and CNR and higher subjective quality scores than the standard-dose group. Moreover, the same patient comparison in the low-dose group between different reconstructions showed that DLIR images had slightly and consistently higher CT values in small vessels, indicating better defined vessels, much lower image noise, higher SNR and CNR and higher subjective quality scores than ASIR-V images (all P < 0.001). CONCLUSIONS: The application of 80-kVp and DLIR allows for significant radiation and dose reduction while further improving image quality in CCTA for overweight patients.