Single-session intervention on growth mindset on negative emotions for university student mental health (U-SIGMA): a protocol of two-armed randomized controlled trial.

BACKGROUND: The university years are a developmentally crucial phase and a peak period for the onset of mental disorders. The beliefs about the changeability of negative emotion may play an important role in help-seeking. The brief digital growth mindset intervention is potentially scalable and acceptable to enhance adaptive coping and help-seeking for mental health needs in university students. We adapted the Single-session Intervention on Growth Mindset for adolescents (SIGMA) to be applied in university students (U-SIGMA). This protocol introduces a two-armed waitlist randomized controlled trial study to examine the effectiveness and acceptability of U-SIGMA in promoting help-seeking among university students in the Greater Bay Area. METHODS: University students (N = 250, ages 18-25) from universities in the Greater Bay Area will be randomized to either the brief digital growth mindset intervention group or the waitlist control group. Participants will report on the mindsets of negative emotions, perceived control over anxiety, attitude toward help-seeking, physical activity, hopelessness, psychological well-being, depression, anxiety, and perceived stress at baseline and the 2-week and 8-week follow-ups through web-based surveys. A 30-min digital intervention will be implemented in the intervention group, with a pre- and post-intervention survey collecting intervention feedback, while the control group will receive the link for intervention after 8 weeks. DISCUSSION: This protocol introduces the implementation plan of U-SIMGA in multi-cities of the Greater Bay Area. The findings are expected to help provide pioneer evidence for the effectiveness and acceptability of the brief digital intervention for university students in the Chinese context and beyond and contribute to the development of accessible and effective prevention and early intervention for university students' mental health. TRIAL REGISTRATION: HKU Clinical Trials Registry: HKUCTR-3012; Registered 14 April 2023.  http://www.hkuctr.com/Study/Show/7a3ffbc0e03f4d1eac0525450fc5187e .

Mouse models of pediatric high-grade gliomas with MYCN amplification reveal intratumoral heterogeneity and lineage signatures.

Pediatric high-grade gliomas of the subclass MYCN (HGG-MYCN) are highly aggressive tumors frequently carrying MYCN amplifications, TP53 mutations, or both alterations. Due to their rarity, such tumors have only recently been identified as a distinct entity, and biological as well as clinical characteristics have not been addressed specifically. To gain insights into tumorigenesis and molecular profiles of these tumors, and to ultimately suggest alternative treatment options, we generated a genetically engineered mouse model by breeding hGFAP-cre::Trp53Fl/Fl::lsl-MYCN mice. All mice developed aggressive forebrain tumors early in their lifetime that mimic human HGG-MYCN regarding histology, DNA methylation, and gene expression. Single-cell RNA sequencing revealed a high intratumoral heterogeneity with neuronal and oligodendroglial lineage signatures. High-throughput drug screening using both mouse and human tumor cells finally indicated high efficacy of Doxorubicin, Irinotecan, and Etoposide as possible therapy options that children with HGG-MYCN might benefit from.

The long non-coding RNA OTX2-AS1 promotes tumor growth and predicts response to BCL-2 inhibition in medulloblastoma.

PURPOSE: Primary brain tumors are a leading cause of cancer-related death in children, and medulloblastoma is the most common malignant pediatric brain tumor. The current molecular characterization of medulloblastoma is mainly based on protein-coding genes, while little is known about the involvement of long non-coding RNAs (lncRNAs). This study aimed to elucidate the role of the lncRNA OTX2-AS1 in medulloblastoma. METHODS: Analyses of DNA copy number alterations, methylation profiles, and gene expression data were used to characterize molecular alterations of OTX2-AS1 in medulloblastoma tissue samples. In vitro analyses of medulloblastoma cell models and orthotopic in vivo experiments were carried out for functional characterization of OTX2-AS1. High-throughput drug screening was employed to identify pharmacological inhibitors, while proteomics and metabolomics analyses were performed to address potential mechanisms of drug action. RESULTS: We detected amplification and consecutive overexpression of OTX2 and OTX2-AS1 in a subset of medulloblastomas. In addition, OTX2-AS1 promoter methylation was linked to OTX2-AS1 expression. OTX2-AS1 knockout reduced medulloblastoma cell viability and cell migration in vitro and prolonged survival in the D283 orthotopic medulloblastoma mouse xenograft model. Pharmacological inhibition of BCL-2 suppressed the growth of OTX2-AS1 overexpressing medulloblastoma cells in vitro. CONCLUSIONS: Our study revealed a pro-tumorigenic role of OTX2-AS1 in medulloblastoma and identified BCL-2 inhibition as a potential therapeutic approach to target OTX2-AS1 overexpressing medulloblastoma cells.

Atypical chronic inflammatory demyelinating polyradiculoneuropathy with ophthalmoplegia and anti-sulfatide IgM positivity.

BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a heterogeneous group of chronic immune-mediated polyradiculoneuropathies. The clinical presentation of CIDP is mainly characterized by a classic peripheral demyelinating sensory-motor type and persists for a minimum of 2 months. However, CIDP may also present with atypical symptoms.Case presentation: This report presents the case of a patient with CIDP with ophthalmoplegia and anti-sulfatide IgM antibodies. Maintenance intravenous immunoglobulin and glucocorticoid therapies were administered to the patient in accordance with the clinical, laboratory, and electrophysiological findings, which were indicative of CIDP. The treatment partially improved the symptoms, and no recurrence was detected throughout the 3-month monitoring phase. CONCLUSIONS: This study combines a retrospective analysis and a literature review to explore the possible mechanism of CIDP.

First Report on Choanephora cucurbitarum Causing Choanephora Rot in Chenopodium Plants and Its Sensitivity to Fungicide.

Choanephora rot of Chenopodium plants (CRC) was observed at the flowering stages in seven plantations of Shanxi Province, China. CRC had caused leaf, stem, and panicle neck rot of C. quinoa, panicle neck and stem rot of C. formosanum, and stem rot of C. album. Typical symptoms included water-soaked, rapid soft rotting, and abundant sporulation on the whole panicle necks, stems, and leaves. Based on morphological characteristics, phylogenetic analyses, and pathogenicity tests, the pathogens were identified as Choanephoraceae cucurbitarum. Sporangiola and sporangiospore of C. cucurbitarum germinated at 30 °C and were able to germinate by two h post-inoculation (hpi). The germination rates of sporangiola and sporangiospore significantly increased at 3 to 4 hpi, and the germination rates ranged from 91.53 to 97.67%. The temperature had a significant effect on the pathogenicity of C. cucurbitarum the optimum pathogenic temperatures for stems of C. quinoa, C. formosanum and C. album were 30 °C after one day post-inoculation. Choanephoraceae cucurbitarum could infect white and red quinoa panicle necks between 20 and 30 °C, and the average lesion lengths were 0.21 to 3.62 cm. Among the five tested fungicides (boscalid, dimethomorph, isopyrazam, propiconazole, and tebuconazole), isopyrazam showed higher sensitivity to sporangiola germination of C. cucurbitarum, with an EC50 value of 0.6550 µg/mL. Isopyrazam and tebuconazole strongly inhibited the sporangiospore germination of C. cucurbitarum, which showed EC50 values of 0.4406 and 0.3857 µg/mL. To our knowledge, the present study found for the first time that C. cucurbitarum is a pathogen causing panicle neck of C. formosanum and stem rot of C. formosanum and C. album, while CRC first appeared in the quinoa panicle necks, and gradually expanded to stems and leaves.

Integrative multi-omics reveals two biologically distinct groups of pilocytic astrocytoma.

Pilocytic astrocytoma (PA), the most common pediatric brain tumor, is driven by aberrant mitogen-activated protein kinase signaling most commonly caused by BRAF gene fusions or activating mutations. While 5-year overall survival rates exceed 95%, tumor recurrence or progression constitutes a major clinical challenge in incompletely resected tumors. Here, we used similarity network fusion (SNF) analysis in an integrative multi-omics approach employing RNA transcriptomic and mass spectrometry-based proteomic profiling to molecularly characterize PA tissue samples from 62 patients. Thereby, we uncovered that PAs segregated into two molecularly distinct groups, namely, Group 1 and Group 2, which were validated in three non-overlapping cohorts. Patients with Group 1 tumors were significantly younger and showed worse progression-free survival compared to patients with group 2 tumors. Ingenuity pathways analysis (IPA) and gene set enrichment analysis (GSEA) revealed that Group 1 tumors were enriched for immune response pathways, such as interferon signaling, while Group 2 tumors showed enrichment for action potential and neurotransmitter signaling pathways. Analysis of immune cell-related gene signatures showed an enrichment of infiltrating T Cells in Group 1 versus Group 2 tumors. Taken together, integrative multi-omics of PA identified biologically distinct and prognostically relevant tumor groups that may improve risk stratification of this single pathway driven tumor type.

Bitter Almond Albumin ACE-Inhibitory Peptides: Purification, Screening, and Characterization In Silico, Action Mechanisms, Antihypertensive Effect In Vivo, and Stability.

Almond expeller is an undeveloped reservoir of bioactive peptides. In the current study, a zinc ion ligand Arg-Pro-Pro-Ser-Glu-Asp-Glu-Asp-Gln-Glu (RPPSEDEDQE) offering a noncompetitive inhibitory effect on ACE (IC50: 205.50 µmol·L-1) was identified from almond albumin hydrolysates via papain and thermolysin hydrolysis, subsequent chromatographic separation, and UPLC-Q-TOF-MS/MS analysis. Molecular docking simulated the binding modes of RPPSEDEDQE to ACE and showed the formation of hydrogen bonds between RPPSEDEDQE and seven active residues of ACE. Moreover, RPPSEDEDQE could bind to fifteen active sites of ACE by hydrophobic interactions, and link with the His387 and zinc ions of the zinc tetrahedral coordination. Ultraviolet wavelength scanning and Fourier-transformed infrared spectroscopy analysis revealed that RPPSEDEDQE can provide multiple binding sites for zinc ions. However, RPPSEDEDQE cannot bind with any central pocket of ACE, which was evidenced by an inhibition kinetics experiment. Additionally, the zinc-chelating capacity and inhibiting ability against ACE of RPPSEDEDQE were both not significantly reduced by the hydrolysis of gastrointestinal enzymes. A moderate to high dose of RPPSEDEDQE (100-150 mg·kg bw-1) significantly reduced the systolic and diastolic blood pressure of spontaneous hypertensive rats, but chelation with zinc ions decreased its antihypertensive efficiency. These results indicate that bitter almond albumin peptides may be used for lowering blood pressure.

B-seco Limonoids with anti-inflammatory activity from Tetradium fraxinifolium (Hook.) T.G.Hartley.

Fraxinifolines A-F (1-6), six new B-seco limonoids, together with four known A,D-di-seco ones, were isolated from the twigs with leaves of Tetradium fraxinifolium. Their structures with absolute configurations were elucidated on the basis of analysis of MS, NMR, single-crystal X-ray diffraction and biogenetic pathway. An anti-inflammatory bioassay in vitro showed limonoids 1-3 had significant immunosuppressive effect against the production of pro-inflammatory cytokines (IL-1ß and/or TNF-α) in lipopolysaccharide (LPS)-stimulated RAW264.7 cells.

Study on the In Silico Screening and Characterization, Inhibition Mechanisms, Zinc-Chelate Activity, and Stability of ACE-Inhibitory Peptides Identified in Naked Oat Bran Albumin Hydrolysates.

In this study, naked oat bran albumin hydrolysates (NOBAH) were subjected to gel chromatography with Sephadex G-15, reverse phase-high liquid performance separation, and UPLC-ESI-MS/MS identification. Six safe peptides including Gly-Thr-Thr-Gly-Gly-Met-Gly-Thr (GTTGGMGT), Gln-Tyr-Val-Pro-Phe (QYVPF), Gly-Ala-Ala-Ala-Ala-Leu-Val (GAAAALV), Gly-Tyr-His-Gly-His (GYHGH), Gly-Leu-Arg-Ala-Ala-Ala-Ala-Ala-Ala-Glu-Gly-Gly (GLRAAAAAAEGG), and Pro-Ser-Ser-Pro-Pro-Ser (PSSPPS) were identified. Next, in silico screening demonstrated that QYVPF and GYHGH had both angiotensin-I-converting enzyme (ACE) inhibition activity (IC50: 243.36 and 321.94 µmol/L, respectively) and Zinc-chelating ability (14.85 and 0.32 mg/g, respectively). The inhibition kinetics demonstrated that QYVPF and GYHGH were both uncompetitive inhibitors of ACE. Molecular docking showed that QYVPF and GYHGH could bind, respectively, three and five active residues of ACE with short hydrogen bonds (but not belonging to any central pocket). QYVPF and GYHGH could bind, respectively, twenty-two and eleven residues through hydrophobic interactions. Moreover, GYHGH was able to affect zinc tetrahedral coordination in ACE by interacting with His383. The inhibition activities of QYVPF and GYHGH toward ACE were relatively resistant to gastrointestinal digestion. GYHGH improved zinc solubility in the intestines (p > 0.05) because its amino and carboxyl groups were chelating sites for zinc ions. These results suggest the potential applications of naked oat peptides for potential antihypertension or zinc fortification.

UBE2C promotes leptomeningeal dissemination and is a therapeutic target in brain metastatic disease.

Background: Despite current improvements in systemic cancer treatment, brain metastases (BM) remain incurable, and there is an unmet clinical need for effective targeted therapies. Methods: Here, we sought common molecular events in brain metastatic disease. RNA sequencing of thirty human BM identified the upregulation of UBE2C, a gene that ensures the correct transition from metaphase to anaphase, across different primary tumor origins. Results: Tissue microarray analysis of an independent BM patient cohort revealed that high expression of UBE2C was associated with decreased survival. UBE2C-driven orthotopic mouse models developed extensive leptomeningeal dissemination, likely due to increased migration and invasion. Early cancer treatment with dactolisib (dual PI3K/mTOR inhibitor) prevented the development of UBE2C-induced leptomeningeal metastases. Conclusions: Our findings reveal UBE2C as a key player in the development of metastatic brain disease and highlight PI3K/mTOR inhibition as a promising anticancer therapy to prevent late-stage metastatic brain cancer.

A systematic exploration of attentional load effects on the C1 ERP component.

The C1 ERP component reflects the earliest visual processing in V1. However, it remains debated whether attentional load can influence it or not. We conducted two EEG experiments to investigate the effect of attentional load on the C1. Task difficulty was manipulated at fixation using an oddball detection task that was either easy (low load) or difficult (high load), while the distractor was presented in the upper visual field (UVF) to score the C1. In Experiment 1, we used a block design and the stimulus onset asynchrony (SOA) between the central stimulus and the peripheral distractor was either short or long. In Experiment 2, task difficulty was manipulated on a trial-by-trial basis using a visual cue, and the peripheral distractor was presented either before or after the central stimulus. The results showed that the C1 was larger in the high compared to the low load condition irrespective of SOA in Experiment 1. In Experiment 2, no significant load modulation of the C1 was observed. However, we found that the contingent negative variation (CNV) was larger in the low compared to the high load condition. Moreover, the C1 was larger when the peripheral distractor was presented after than before the central stimulus. Combined together, these results suggest that different top-down control processes can influence the initial feedforward stage of visual processing in V1 captured by the C1 ERP component.

Single von Willebrand factor C-domain protein confers host defense against white spot syndrome virus by functioning as a pattern recognition receptor in Macrobrachium nipponense.

The single von Willebrand factor C-domain proteins (SVWCs), also known as Vago, are primarily found in arthropods. Their expression was induced by nutritional status, bacterial and viral infections. Despite the prominence of SVWCs in antiviral immunity, the detailed molecular mechanisms remain poorly explained. SVWC has been proposed to elicit antiviral activities through its function as an interferon analog. In contrast, herein, we illustrate that an SVWC homolog from Macrobrachium nipponense (MnSVWC) confers host defense against white spot syndrome virus (WSSV) and covert mortality nodavirus (CMNV) as a pattern recognition receptor (PRR). qRT-PCR analyses demonstrated that the expression of MnSVWC was enhanced upon WSSV infection in all detected tissues, including gills, nerve cords, and hemocytes. Coating WSSV with recombinant MnSVWC (rMnSVWC) promoted the phagocytic activity of hemocytes and subsequent clearance of invasive WSSV from the prawn. On the other hand, the knockdown of MnSVWC with RNAi improved the proliferation ability of WSSV and CMNV in the prawn. Analysis of ELISA and Co-immunoprecipitation (Co-IP) showed that rMnSVWC could bind WSSV by interacting with the vesicle proteins VP26 and VP28. Co-IP analysis verified the interaction between MnSVWC and calmodulin, which implies a vesicle protein-SVWC-calmodulin-clathrin-dependent mechanism underlying the hemocyte-mediated phagocytosis against WSSV. Subsequently, MnSVWC was recognized to activate the expression of transcription factor STAT and an interferon-stimulating gene Viperin, illustrating its involvement in modulating humoral immunity via activation of the JAK/STAT pathway after WSSV infection. These findings indicate that MnSVWC could bind to WSSV as a PRR and participate in the promotion of hemocyte-mediated phagocytosis and the activation of the JAK/STAT pathway in prawns.

Disulfide Bond-Based SN38 Prodrug Nanoassemblies with High Drug Loading and Reduction-Triggered Drug Release for Pancreatic Cancer Therapy.

Purpose: Chemotherapy is a significant and effective therapeutic strategy that is frequently utilized in the treatment of cancer. Small molecular prodrug-based nanoassemblies (SMPDNAs) combine the benefits of both prodrugs and nanomedicine into a single nanoassembly with high drug loading, increased stability, and improved biocompatibility. Methods: In this study, a disulfide bond inserted 7-ethyl-10-hydroxycamptothecin (SN38) prodrug was rationally designed and then used to prepare nanoassemblies (SNSS NAs) that were selectively activated by rich glutathione (GSH) in the tumor site. The characterization of SNSS NAs and the in vitro and in vivo evaluation of their antitumor effect on a pancreatic cancer model were performed. Results: In vitro findings demonstrated that SNSS NAs exhibited GSH-induced SN38 release and cytotoxicity. SNSS NAs have demonstrated a passive targeting effect on tumor tissues, a superior antitumor effect compared to irinotecan (CPT-11), and satisfactory biocompatibility with double dosage treatment. Conclusion: The SNSS NAs developed in this study provide a new method for the preparation of SN38-based nano-delivery systems with improved antitumor effect and biosafety.

Tacedinaline (CI-994), a class I HDAC inhibitor, targets intrinsic tumor growth and leptomeningeal dissemination in MYC-driven medulloblastoma while making them susceptible to anti-CD47-induced macrophage phagocytosis via NF-kB-TGM2 driven tumor inflammation.

BACKGROUND: While major advances have been made in improving the quality of life and survival of children with most forms of medulloblastoma (MB), those with MYC-driven tumors (Grp3-MB) still suffer significant morbidity and mortality. There is an urgent need to explore multimodal therapeutic regimens which are effective and safe for children. Large-scale studies have revealed abnormal cancer epigenomes caused by mutations and structural alterations of chromatin modifiers, aberrant DNA methylation, and histone modification signatures. Therefore, targeting epigenetic modifiers for cancer treatment has gained increasing interest, and inhibitors for various epigenetic modulators have been intensively studied in clinical trials. Here, we report a cross-entity, epigenetic drug screen to evaluate therapeutic vulnerabilities in MYC amplified MB, which sensitizes them to macrophage-mediated phagocytosis by targeting the CD47-signal regulatory protein α (SIRPα) innate checkpoint pathway. METHODS: We performed a primary screen including 78 epigenetic inhibitors and a secondary screen including 20 histone deacetylase inhibitors (HDACi) to compare response profiles in atypical teratoid/rhabdoid tumor (AT/RT, n=11), MB (n=14), and glioblastoma (n=14). This unbiased approach revealed the preferential activity of HDACi in MYC-driven MB. Importantly, the class I selective HDACi, CI-994, showed significant cell viability reduction mediated by induction of apoptosis in MYC-driven MB, with little-to-no activity in non-MYC-driven MB, AT/RT, and glioblastoma in vitro. We tested the combinatorial effect of targeting class I HDACs and the CD47-SIRPa phagocytosis checkpoint pathway using in vitro phagocytosis assays and in vivo orthotopic xenograft models. RESULTS: CI-994 displayed antitumoral effects at the primary site and the metastatic compartment in two orthotopic mouse models of MYC-driven MB. Furthermore, RNA sequencing revealed nuclear factor-kB (NF-κB) pathway induction as a response to CI-994 treatment, followed by transglutaminase 2 (TGM2) expression, which enhanced inflammatory cytokine secretion. We further show interferon-γ release and cell surface expression of engulfment ('eat-me') signals (such as calreticulin). Finally, combining CI-994 treatment with an anti-CD47 mAb targeting the CD47-SIRPα phagocytosis checkpoint enhanced in vitro phagocytosis and survival in tumor-bearing mice. CONCLUSION: Together, these findings suggest a dynamic relationship between MYC amplification and innate immune suppression in MYC amplified MB and support further investigation of phagocytosis modulation as a strategy to enhance cancer immunotherapy responses.

The person-to-person transmission landscape of the gut and oral microbiomes.

The human microbiome is an integral component of the human body and a co-determinant of several health conditions1,2. However, the extent to which interpersonal relations shape the individual genetic makeup of the microbiome and its transmission within and across populations remains largely unknown3,4. Here, capitalizing on more than 9,700 human metagenomes and computational strain-level profiling, we detected extensive bacterial strain sharing across individuals (more than 10 million instances) with distinct mother-to-infant, intra-household and intra-population transmission patterns. Mother-to-infant gut microbiome transmission was considerable and stable during infancy (around 50% of the same strains among shared species (strain-sharing rate)) and remained detectable at older ages. By contrast, the transmission of the oral microbiome occurred largely horizontally and was enhanced by the duration of cohabitation. There was substantial strain sharing among cohabiting individuals, with 12% and 32% median strain-sharing rates for the gut and oral microbiomes, and time since cohabitation affected strain sharing more than age or genetics did. Bacterial strain sharing additionally recapitulated host population structures better than species-level profiles did. Finally, distinct taxa appeared as efficient spreaders across transmission modes and were associated with different predicted bacterial phenotypes linked with out-of-host survival capabilities. The extent of microorganism transmission that we describe underscores its relevance in human microbiome studies5, especially those on non-infectious, microbiome-associated diseases.

Extension Peptide of Plant Ferritin from Setaria italica Presents a Novel Fold.

The extension peptide (EP) is the most distinctive feature of mature plant ferritin. Some EPs have exhibited serine-like protease activity, which is associated with iron uptake and release. EP forms a helix and a long loop, followed by a conserved core helical bundle. However, whether the EP adopts a stable or uniform folding pattern in all plants remains unclear. To clarify this, we investigated the crystal structure of ferritin-1 from Setaria italica (SiFer1), a type of monocotyledon. In our structure of SiFer1, the EP is different from other EPs in other solved structures of plant ferritins and consisted of a pair of ß-sheets, a shorter helix, and two loops, which masks two hydrophobic pockets on the outer surface of every subunit. Furthermore, sequence analysis and structure comparison suggest that the EPs in ferritins from monocotyledons may adopt a novel fold pattern, and the conformations of EPs in ferritins are alterable among different plant species. Furthermore, additional eight iron atoms were first founded binding in the fourfold channels, demonstrating the vital function of fourfold channels in iron diffusion. In all, our structure provides new clues for understanding plant ferritins and the functions of the EP.

Effectiveness of couple-based interventions for prostate cancer patients and their spouses on their quality of life: a systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis aimed to synthesize the evidence on the effect of couple-based interventions on quality of life (QOL) among prostate cancer patients and their spouses. METHOD: Six English databases and two Chinese databases were systematically searched to identify relevant RCTs that examined the effect of couple-based interventions on QOL. The data from the included studies were extracted by two independent reviewers using a standardized data extraction form. Methodological quality was assessed by using the Cochrane Risk of Bias Tool. Meta-analysis was conducted among the suitable studies that the available data were sufficient. RESULTS: One thousand ninety-five studies were identified, and 11 studies met the inclusion criteria for qualitative synthesis and 7 studied for meta-analysis. Couple-based interventions involve different formats of physical and psychosocial interventions. Physical exercise-based interventions were popular among couples, and these interventions had the highest level of adherence among all interventions examined herein. However, the meta-analysis of total QOL and physical and mental health revealed a non-significant effect on both prostate cancer patients and their spouses. More RCTs examining couple-based interventions may be needed in developing countries, especially in Asian countries. CONCLUSION: Couple-based interventions had non-significant effect on improving the total QOL and physical and mental health of prostate cancer patients and their spouses. However, the current evidence is limited because the sample size of the studies is small. Thus, more studies with large sample sizes need to be included to detect the efficacy of couple-based interventions on prostate cancer patients and their spouses.

A novel promising diagnosis model for colorectal advanced adenoma and carcinoma based on the progressive gut microbiota gene biomarkers.

BACKGROUND: Colorectal cancer (CRC), a commonly diagnosed cancer often develops slowly from benign polyps called adenoma to carcinoma. Altered gut microbiota is implicated in colorectal carcinogenesis. It is warranted to find non-invasive progressive microbiota biomarkers that can reflect the dynamic changes of the disease. This study aimed to identify and evaluate potential progressive fecal microbiota gene markers for diagnosing advanced adenoma (AA) and CRC. RESULTS: Metagenome-wide association was performed on fecal samples from different cohorts of 871 subjects (247 CRC, 234 AA, and 390 controls). We characterized the gut microbiome, identified microbiota markers, and further constructed a colorectal neoplasms classifier in 99 CRC, 94 AA, and 62 controls, and validated the results in 185 CRC, 140 AA, and 291 controls from 3 independent cohorts. 21 species and 277 gene markers were identified whose abundance was significantly increased or decreased from normal to AA and CRC. The progressive gene markers were distributed in metabolic pathways including amino acid and sulfur metabolism. A diagnosis model consisting of four effect indexes was constructed based on the markers, the sensitivities of the Adenoma Effect Index 1 for AA, Adenoma Effect Index 2 for high-grade dysplasia (HGD) adenoma were 71.3% and 76.5%, the specificities were 90.5% and 90.3%, respectively. CRC Effect Index 1 for all stages of CRC and CRC Effect Index 2 for stage III-IV CRC to predict CRC yielded an area under the curve (AUC) of 0.839 (95% CI 0.804-0.873) and 0.857 (95% CI 0.793-0.921), respectively. Combining with fecal immunochemical test (FIT) significantly improved the sensitivity of CRC Effect Index 1 and CRC Effect Index 2 to 96.7% and 100%. CONCLUSIONS: This study reports the successful diagnosis model establishment and cross-region validation for colorectal advanced adenoma and carcinoma based on the progressive gut microbiota gene markers. The results suggested that the novel diagnosis model can significantly improve the diagnostic performance for advanced adenoma.

Triggers and Coping Strategies for Fear of Cancer Recurrence in Cancer Survivors: A Qualitative Study.

BACKGROUND: Fear of cancer recurrence (FCR) has been demonstrated to be one of the most frequently reported unmet psychological needs among cancer survivors. The aim of this study was to explore and describe the potential triggers and coping strategies for FCR in Chinese cancer survivors. METHODS: The study process was conducted using an interpretive phenomenological research method, and Chinese cancer survivors were interviewed face-to-face in a semi-structured interview, using purposive sampling combined with a maximum variance sampling strategy, and the interviews were transcribed, organized, and analyzed by applying Giorgi analysis with the help of NVivo11 software. RESULTS: A total of 10 participants, 4 males and 6 females, were interviewed. Three themes emerged in terms of potential triggers for FCR: (1) intrusive thoughts; (2) disease symptoms; and (3) awaiting medical examination. Two themes regarding positive coping and avoidance coping emerged with regard to coping strategies adopted by cancer survivors when experiencing FCR. Under these 2 themes were 5 sub-themes: (1) seeking medical support; (2) self-health management; (3) spiritual coping; (4) unaccompanied toleration; and (5) attention shifting. CONCLUSION: FCR as the most common psychological problem for cancer survivors, and it should be given more attention. Early identification and precise intervention for potential triggers of FCR may prevent the emergence and development of FCR. The guidance toward and cultivation of positive coping strategies when cancer survivors experience FCR could be an important direction in future nursing education.

Alkaloid Derivative (Z)-3ß-Ethylamino-Pregn-17(20)-en Inhibits Triple-Negative Breast Cancer Metastasis and Angiogenesis by Targeting HSP90α.

Metastasis is an important cause of cancer-related death. Previous studies in our laboratory found that pregnane alkaloids from Pachysandra terminalis had antimetastatic activity against breast cancer cells. In the current study, we demonstrated that treatment with one of the alkaloid derivatives, (Z)-3ß-ethylamino-pregn-17(20)-en (1), led to the downregulation of the HIF-1α/VEGF/VEGFR2 pathway, suppressed the phosphorylation of downstream molecules Akt, mTOR, FAK, and inhibited breast cancer metastasis and angiogenesis both in vitro and in vivo. Furthermore, the antimetastasis and antiangiogenesis effects of 1 treatment (40 mg/kg) were more effective than that of Sorafenib (50 mg/kg). Surface plasmon resonance (SPR) analysis was performed and the result suggested that HSP90α was a direct target of 1. Taken together, our results suggested that compound 1 might represent a candidate antitumor agent for metastatic breast cancer.