Topological chiral crystals with helicoid-arc quantum states.

The quantum behaviour of electrons in materials is the foundation of modern electronics and information technology1-11, and quantum materials with topological electronic and optical properties are essential for realizing quantized electronic responses that can be used for next generation technology. Here we report the first observation of topological quantum properties of chiral crystals6,7 in the RhSi family. We find that this material class hosts a quantum phase of matter that exhibits nearly ideal topological surface properties originating from the crystals' structural chirality. Electrons on the surface of these crystals show a highly unusual helicoid fermionic structure that spirals around two high-symmetry momenta, indicating electronic topological chirality. The existence of bulk multiply degenerate band fermions is guaranteed by the crystal symmetries; however, to determine the topological invariant or charge in these chiral crystals, it is essential to identify and study the helicoid topology of the arc states. The helicoid arcs that we observe on the surface characterize the topological charges of ±2, which arise from bulk higher-spin chiral fermions. These topological conductors exhibit giant Fermi arcs of maximum length (π), which are orders of magnitude larger than those found in known chiral Weyl fermion semimetals5,8-11. Our results demonstrate an electronic topological state of matter on structurally chiral crystals featuring helicoid-arc quantum states. Such exotic multifold chiral fermion semimetal states could be used to detect a quantized photogalvanic optical response, the chiral magnetic effect and other optoelectronic phenomena predicted for this class of materials6.

Anus preservation in low rectal adenocarcinoma based on MMR/MSI status (APRAM): a study protocol for a randomised, controlled, open-label, multicentre phase III trial.

BACKGROUND: Anus preservation has been a challenge in the treatment of patients with low rectal adenocarcinoma (within 5 cm from the anal verge) because it is difficult to spare the anus with its functioning sphincter complex under the safe margin of tumour resection. Patients with dMMR/MSI-H can achieve a favourable complete response (CR) rate by using a single immune checkpoint inhibitor. For patients with pMMR/MSS/MSI-L, intensified neoadjuvant three-drug chemotherapy may be the preferred option for anal preservation. In addition, the watch and wait (W&W) strategy has been proven safe and feasible for patients with rectal cancer who achieve a clinical complete response (cCR). Therefore, we initiated this clinical trial to explore the optimal neoadjuvant treatment pattern for patients with low locally advanced rectal cancer (LARC) with different MMR/MSI statuses, aiming to achieve a higher cCR rate with the W&W strategy and ultimately provide more patients with a chance of anus preservation. METHODS: This is a randomised, controlled, open-label, multicentre phase III trial. Patients with clinical stage T2-4 and/or N + tumours located within 5 cm from the anal verge are considered eligible. Based on the results of pathological biopsy, the patients are divided into two groups: dMMR/MSI-H and pMMR/MSS. Patients in the dMMR/MSI-H group will be randomly allocated in a 1:1 ratio to either arm A (monoimmunotherapy) or arm B (short-course radiotherapy followed by monoimmunotherapy). Patients in the pMMR/MSS group will be initially treated with long-term pelvic radiation with concurrent capecitabine combined with irinotecan. Two weeks after the completion of chemoradiotherapy (CRT), the patients will be randomly allocated in a 1:1 ratio to arm C (XELIRI six cycle regime) or arm D (FOLFIRINOX nine cycle regime). The irinotecan dose will be adjusted according to the UGT1A1-genotype. After treatment, a comprehensive assessment will be performed to determine whether a cCR has been achieved. If achieved, the W&W strategy will be adopted; otherwise, total mesorectal excision (TME) will be performed. The primary endpoint is cCR with the maintenance of 12 months at least, determined using digital rectal examination, endoscopy, and rectal MRI or PET/CT as a supplementary method. DISCUSSION: APRAM will explore the best anus preservation model for low LARC, combining the strategies of consolidation chemotherapy, immunotherapy, and short-course radiotherapy, and aims to preserve the anus of more patients using W&W. Our study provides an accurate individual treatment mode based on the MMR/MSI status for patients with low LARC, and more patients will receive the opportunity for anus preservation under our therapeutic strategy, which would transform into long-term benefits. TRIAL REGISTRATION: Clinicaltrials.gov NCT05669092 (Registered 28th Nov 2022).

Sodium-Glucose Co-Transporter-2 Inhibitor Empagliflozin Attenuates Sorafenib-Induced Myocardial Inflammation and Toxicity.

Environmental antineoplastics such as sorafenib may pose a risk to humans through water recycling, and the increased risk of cardiotoxicity is a clinical issue in sorafenib users. Thus, developing strategies to prevent sorafenib cardiotoxicity is an urgent work. Empagliflozin, as a sodium-glucose co-transporter-2 (SGLT2) inhibitor for type 2 diabetes control, has been approved for heart failure therapy. Still, its cardioprotective effect in the experimental model of sorafenib cardiotoxicity has not yet been reported. Real-time quantitative RT-PCR (qRT-PCR), immunoblot, and immunohistochemical analyses were applied to study the effect of sorafenib exposure on cardiac SGLT2 expression. The impact of empagliflozin on cell viability was investigated in the sorafenib-treated cardiomyocytes using Alamar blue assay. Immunoblot analysis was employed to delineate the effect of sorafenib and empagliflozin on ferroptosis/proinflammatory signaling in cardiomyocytes. Ferroptosis/DNA damage/fibrosis/inflammation of myocardial tissues was studied in mice with a 28-day sorafenib ± empagliflozin treatment using histological analyses. Sorafenib exposure significantly promoted SGLT2 upregulation in cardiomyocytes and mouse hearts. Empagliflozin treatment significantly attenuated the sorafenib-induced cytotoxicity/DNA damage/fibrosis in cardiomyocytes and mouse hearts. Moreover, GPX4/xCT-dependent ferroptosis as an inducer for releasing high mobility group box 1 (HMGB1) was also blocked by empagliflozin administration in the sorafenib-treated cardiomyocytes and myocardial tissues. Furthermore, empagliflozin treatment significantly inhibited the sorafenib-promoted NFκB/HMGB1 axis in cardiomyocytes and myocardial tissues, and sorafenib-stimulated proinflammatory signaling (TNF-α/IL-1ß/IL-6) was repressed by empagliflozin administration. Finally, empagliflozin treatment significantly attenuated the sorafenib-promoted macrophage recruitments in mouse hearts. In conclusion, empagliflozin may act as a cardioprotective agent for humans under sorafenib exposure by modulating ferroptosis/DNA damage/fibrosis/inflammation. However, further clinical evidence is required to support this preclinical finding.

Use of iTRAQ-based quantitative proteomic identification of CHGA and UCHL1 correlated with lymph node metastasis in colorectal carcinoma.

Metastatic dissemination of colorectal cancer (CRC), the third most common cancer type, is responsible for CRC deaths. Understanding the transition of lymph node metastasis (LNM) from Stage II to Stage III is beneficial in the prognosis and intervention of CRC. In this study, a quantitative proteomic survey was conducted to investigate the LNM-associated proteins and evaluate the clinicopathological characteristics of these target proteins in CRC. By using the LC-MS/MS iTRAQ technology, we analysed the proteomic changes between LMN II and LMN III. Fresh tumours from the CRC specimens consisting of 12 node-negative (Stage II) and 12 node-positive (Stage III) cases were analysed by LC-MS/MS iTRAQ proteome analysis. Subsequently, tissue microarray with immunohistochemistry staining was conducted to access the clinicopathological characteristics of these proteins in 116 paraffin-embedded CRC samples, each for non-LNM and LNM CRC. To study the effects of the differentially expressed proteins on the potential mechanism, Boyden chamber assay, flow cytometry and shRNA-based assessments were conducted to examine the role of the epithelial-mesenchymal transition (EMT) and the invasiveness of CRC cells and others in vivo xenograft mouse model experiments. Forty-eight proteins were found differentially expressed between non-LNM and LNM CRC tissues. Protein abundances of chromogranin-A (CHGA) and ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1) were observed in node-positive CRC (p < 0.05). Knockdown of CHGA and UCHL1 significantly regulate cancer behaviours of HCT-116, including inhibition of cell migration, invasiveness, cell cycle G1/S arrest and reactive oxygen species (ROS) generation. Mechanistically, the CHGA and UCHL1 inactivation displayed decreased levels of UCH-L1, chromogranin A, ß-catenin, cyclin E, twist-1/2, vimentin, MMP-9, N-cadherin and PCNA through the activation of the Rho-GTPase/AKT/NFκB pathways. Histone modification of H3K4 trimethylation of CHGA and UCHL1 promoter were increased to activate their transcription through the signalling transduction such as Rho-GTPase, AKT and NFκB pathways. Our results indicated that UCHL1 and chromogranin A are novel regulators in CRC lymph node metastasis to potentially provide new insights into the mechanism of CRC progression and serve as biomarkers for CRC diagnosis at the metastatic stage.

The COVID-19 pandemic has impeded cytopathology practices and hindered cancer screening and management.

The COVID-19 pandemic has had a global impact on the environment and economy and has affected hospital administration and patient behaviour. Since human-to-human coronavirus transmission occurs via droplets and physical contact, health care professionals are particularly vulnerable to contracting COVID-19. Many cytopathology laboratories updated their workflow, established new standard biosafety protocols, and built digital pathology or telescope platforms to mitigate these risks and deal with the shortage of health care personnel. The COVID-19 pandemic also disrupted medical education-all indoor training events, including conferences, multidisciplinary tumour boards, seminars, and microscope inspections were postponed. As a result, many laboratories now use new web-based applications and platforms to maintain educational programs and multidisciplinary tumour boards. To comply with government directives, health care facilities postponed non-emergency surgeries, reduced the number of routine medical examinations, restricted visitor numbers, and scaled back cancer screening activities, resulting in a sharp decline in cytopathology diagnoses, cancer screening specimens, and molecular testing for cancer. Subsequent misses or delays in the diagnosis and treatment of cancer were not uncommon. This review aims to provide comprehensive summaries of the consequences of the COVID-19 pandemic for cytopathology, particularly in terms of cancer diagnosis, workload, human resources, and molecular testing.

Deep learning-based prediction of mandibular growth trend in children with anterior crossbite using cephalometric radiographs.

BACKGROUND: It is difficult for orthodontists to accurately predict the growth trend of the mandible in children with anterior crossbite. This study aims to develop a deep learning model to automatically predict the mandibular growth result into normal or overdeveloped using cephalometric radiographs. METHODS: A deep convolutional neural network (CNN) model was constructed based on the algorithm ResNet50 and trained on the basis of 256 cephalometric radiographs. The prediction behavior of the model was tested on 40 cephalograms and visualized by equipped with Grad-CAM. The prediction performance of the CNN model was compared with that of three junior orthodontists. RESULTS: The deep-learning model showed a good prediction accuracy about 85%, much higher when compared with the 54.2% of the junior orthodontists. The sensitivity and specificity of the model was 0.95 and 0.75 respectively, higher than that of the junior orthodontists (0.62 and 0.47 respectively). The area under the curve value of the deep-learning model was 0.9775. Visual inspection showed that the model mainly focused on the characteristics of special regions including chin, lower edge of the mandible, incisor teeth, airway and condyle to conduct the prediction. CONCLUSIONS: The deep-learning CNN model could predict the growth trend of the mandible in anterior crossbite children with relatively high accuracy using cephalometric images. The deep learning model made the prediction decision mainly by identifying the characteristics of the regions of chin, lower edge of the mandible, incisor teeth area, airway and condyle in cephalometric images.

Effects of a mobile oral care app on oral mucositis, pain, nutritional status, and quality of life in patients with head and neck cancer: A quasi-experimental study.

AIM: The aim of this work is to explore the effectiveness of a mobile app to support oral mucositis care to improve the nutritional status and reduce the occurrence of oral mucositis of patients with head and neck cancer undergoing concurrent chemoradiotherapy. BACKGROUND: Concurrent chemoradiotherapy is the optimal treatment for head and neck cancer, but oral mucositis and malnutrition are common complications. DESIGN: Quasi-experimental study using a pre-post design was used in this work. METHOD: Participants were recruited from a major regional hospital in Taiwan from July 2018 to July 2020. There were 32 participants in each group: the mobile app group (Intervention Group) or routine care (Control Group). The primary outcome measure was Patient-Generated Subjective Global Assessment (PG-SGA). We also collected data on grade of oral mucositis, painNnumeric Rating Scale (NRS), weight loss, haemoglobin (Hb), albumin and quality of life (QoL). RESULT: The PG-SGA score was significantly lower in the intervention than the control group at all three time points. Hb and albumin decreased less significantly in the intervention than the control group after 2 months. The oral mucositis grade was significantly less severe in the intervention than the control group at all three time points; for the NRS, at T2 and T3. CONCLUSION: Using the mobile app effectively improved nutritional status, alleviated the side effects, and improved the QoL of head and neck cancer patients with concurrent chemoradiotherapy.

Fluoroquinolones Suppress TGF-ß and PMA-Induced MMP-9 Production in Cancer Cells: Implications in Repurposing Quinolone Antibiotics for Cancer Treatment.

BACKGROUND: Fluoroquinolones (FQs) are potent antimicrobials with multiple effects on host cells and tissues. Although FQs can attenuate cancer invasion and metastasis, the underlying molecular mechanisms remain unclear. Matrix metalloproteinase-9 (MMP-9) has functional roles in tumor angiogenesis, invasion, and metastasis, and is associated with cancer progression and poor prognosis, suggesting that inhibitors of MMP-9 activity and transcription are prime candidates for cancer therapy. Despite numerous preclinical data supporting the use of MMP-9 inhibitors as anticancer drugs, the few available examples are not therapeutically useful due to low specificity and off-target effects. We examined the effects of FQs on MMP-9 production in cancer cells following transforming growth factor beta (TGF-ß) and phorbol 12-myristate 13-acetate (PMA) stimulation. EXPERIMENTAL APPROACHES: Using confluent cultures of HepG2 and A549 cells, the effects of FQs (ciprofloxacin, levofloxacin, clinafloxacin, gatifloxacin, and enrofloxacin) on TGF-ß and PMA-induced MMP-9 mRNA expression and production were studied in RNA extracts and culture supernatants, respectively. FQs specifically abrogated TGF-ß and PMA-induced MMP-9 levels and activity in a concentration and time-dependent manner, without affecting other MMPs or proteins involved in epithelial-mesenchymal transition. Additionally, FQs inhibited TGF-ß and PMA-induced cell migration via p38 and cyclic AMP signaling pathways. CONCLUSIONS AND IMPLICATIONS: Overall, we demonstrated that FQs inhibit cancer cell migration and invasion by downregulating MMP-9 expression and revealed the cellular mechanisms underlying their potential value in cancer treatment.

The effectiveness of long-acting injectable antipsychotics versus oral antipsychotics in the maintenance treatment of outpatients with chronic schizophrenia.

OBJECTIVE: To compare the psychiatric service utilization between patients who only received long-acting injectable antipsychotics (LAIAs) and those who only received oral antipsychotics (OAPs) in the maintenance treatment of chronic schizophrenia. METHODS: We constructed a cohort of chronic schizophrenia patients who underwent maintenance treatment from the Taiwan National Health Insurance Research Database in 2011 and followed these patients for 12 months. We included patients who had been diagnosed with schizophrenia for at least 3 years, were not hospitalized in 2011, and had received 1 year of maintenance treatment. Inverse probability of treatment weighting logistic, linear, and negative binomial regression models were used to estimate associated psychiatric services utilization and adjust for covariate imbalances between the LAIAs and OAPs groups. RESULTS: Among 40,194 patients, 948 (2.36%) received only LAIAs and 39,246 (97.64%) received only OAPs. Compared with those who received only OAPs, the sole LAIAs users were associated with a lower percentage of psychiatric hospitalization (8.4% and 5.8%, respectively; odds ratio: 0.63, p < .01), shorter lengths of hospitalization days (82.8 and 65.9, respectively; coefficient [b]: -16.87, p = .03), and fewer emergency room visits (2.3 and 1.8, respectively; b: -0.24, p < .01) per patient. CONCLUSIONS: Chronic schizophrenia patients who received only LAIs had a lower risk of disease relapse and a reduction in psychiatric service utilization than those receiving only OAPs.

The effect of the difference in C2-7 angle on the occurrence of dysphagia after anterior cervical discectomy and fusion with the zero-P implant system.

OBJECTIVES: To investigate the effect of the difference in C2-7 angle on dysphagia after anterior cervical discectomy and fusion (ACDF) with the Zero-P Implant System. METHODS: A retrospective analysis of 181 patients who underwent ACDF with the Zero-P Implant System and had at least one year of follow-up from January 2011 to November 2018 was performed. All patients were divided into a non-dysphagia group and a dysphagia group to explore the effect of the difference between postoperative and preoperative C2-7 angle (dC2-7A) on postoperative dysphagia. At the same time, other possible related factors including the difference between postoperative and preoperative O-C2 angle (dO-C2A), sex, age, body mass index (BMI), intraoperative time, estimated blood loss, diabetes mellitus, hypertension, smoking, alcohol consumption, prevertebral soft-tissue swelling (PSTS), the highest segment involved in the surgery and the levels of surgery segments were analyzed. RESULTS: In total, the non-dysphagia group comprised 139 patients and the dysphagia group comprised 42 patients. The single-factor analysis showed that smoking, PSTS and dC2-7A were significantly different between the two groups (P < 0.05). Spearman's correlation coefficient showed no significant correlation between the degree of dysphagia and dC2-7A (P > 0.05). The results of the multiple-factor analysis with an ordinal logistic regression model showed that smoking, PSTS and dC2-7A were significantly associated with the incidence of dysphagia (P < 0.05). CONCLUSIONS: The postoperative C2-7 angle has an important effect on the occurrence of dysphagia in patients undergoing Zero-P implant system interbody fusion surgery.

Comparison of the effects of rapid maxillary expansion versus Twin Block appliance on mandibular growth in skeletal Class II patients.

BACKGROUND: This is a retrospective study that compares mandibular growth changes in skeletal Class II patients treated by rapid maxillary expansion (RME) and following fixed appliance with those patients treated by Twin-Block (TB) and following fixed appliance. METHODS: Fourteen patients treated by RME and following fixed appliance were included into the RME group. Fifteen patients treated by Twin-Block and following fixed appliance were included into the TB group. Lateral cephalometric radiographs taken before treatment and immediately after fixed appliance treatment were used to evaluate mandibular growth effects. RESULTS: The starting forms of the patients in the two groups were examined to be of good comparability. The mandibular length increased significantly in both groups as measured by Co-Gn, Go-Gn and Ar-Gn, but the TB group didn't show more mandibular growth than the RME group (P > 0.05). Skeletal changes of the mandible in vertical dimension were different in the two groups. The change in FMA was 0.35° in the RME group, while the change was 2.65° in the TB group (P < 0.001). The change in LAFH was 5.14 mm in the RME group, significantly smaller than the change of 10.19 mm in the TB group (P < 0.001). CONCLUSION: The investigated Phase I treatment with RME followed by Phase II treatment of fixed appliance achieved the same increases in sagittal mandibular growth and facial profile improvements as the Twin-Block therapy. The treatment with RME followed by fixed appliance was better for vertical control, while the treatment with Twin-Block followed by fixed appliance significantly increased the mandibular plane angle.

Monthly tegafur-uracil maintenance for increasing relapse-free survival in ypStage III rectal cancer patients after preoperative radiotherapy, radical resection, and 12 postoperative chemotherapy cycles: a retrospective study.

BACKGROUND: Current advancements in neoadjuvant therapy and total mesorectal excision have engendered increased local control. However, the survival benefit of preoperative radiotherapy (RT; 5 × 5 Gy) in rectal cancer patients remains inadequate, primarily because of systemic recurrence. In this retrospective single-center study, the effects of monthly tegafur-uracil maintenance (≥6 cycles) after 12 fluorouracil-based adjuvant chemotherapy cycles on 3-year relapse-free survival (RFS) was estimated in ypStage III rectal cancer patients. METHODS: Of ypStage III rectal cancer patients who received preoperative RT (5 × 5 Gy) in January 2006-December 2015, those who had ypStage III cancer after preoperative radiation, radical resection, and postoperative chemotherapy were enrolled; excluded patients had ypStage I and II rectal cancer, had double cancer, had synchronous distant metastasis, had local excision, received preoperative chemoradiation, and were lost to follow-up within 1 year after cancer treatment. Included patients received either maintenance therapy or observation after postoperative chemotherapy. The primary endpoint was the effect of maintenance therapy on 3-year RFS. We set the median follow-up duration to be 69.7 (range, 15.4-148.3) months. RESULTS: Of 259 ypStage III rectal cancer patients, 102 (59 men and 43 women) were enrolled based on the inclusion criteria. The maintenance and observation groups comprised 55 and 57 patients, respectively (mean age = 62.2 and 65.7 years, respectively; p = 0.185). The 3-year RFS observed in the maintenance group (85.1%) was longer than that observed in the observation group (67.5%; p = 0.039). Multivariate analysis proved the following to be independent prognostic factors for RFS: higher metastatic lymph node ratio (LNR ≥0.3), tegafur-uracil maintenance (≥6 cycles), and lower rectal cancer (< 6 cm from the anal verge). The higher the rectal cancer location (≥6 cm from the anal verge) was, the higher the tegafur-uracil maintenance survival benefit became (p = 0.041). Moreover, lower cancer location (< 6 cm from the anal verge) and LNR ≥0.3 were both associated with a trend of longer RFS after tegafur-uracil maintenance therapy (p = 0.164 and 0.113, respectively). CONCLUSIONS: After the execution of fluorouracil-based adjuvant chemotherapy, administering monthly tegafur-uracil (≥6 cycles) may improve the 3-year RFS of ypStage III rectal cancer patients.

Expression of PRDX6 Correlates with Migration and Invasiveness of Colorectal Cancer Cells.

BACKGROUND/AIMS: Colorectal cancer (CRC) is the third most common type of cancer and the second leading cause of cancer-related deaths worldwide. PRDXs are antioxidant enzymes that play an important role in cell differentiation, proliferation and apoptosis and have diverse functions in malignancy development. However, the mechanism of aberrant overexpression of PRDX6 in CRC remains unclear. METHODS: Boyden chamber assay, flow cytometry and a lentiviral shRNA targeting PRDX6 and transient transfection with pCMV-6-PRDX6 plasmid were used to examine the role of PRDX6 in the proliferation capacity and invasiveness of CRC cells. Immunohistochemistry (IHC) with tissue array containing 40 paraffin- embedded CRC tissue specimens and Western blot assays were used to detect target proteins. RESULTS: PRDX6 was significantly up-expressed in different comparisons of metastasis of colorectal adenomas in node-positive CRC (P = 0.03). In in vitro HCT-116, PRDX6 silencing markedly suppressed CRC cell migration and invasiveness while also inducing cell cycle arrest as well as the generation of reactive oxygen species (ROS); specific overexpression of PRDX6 had the opposite effect. Mechanistically, the PRDX6 inactivation displayed decreased levels of PRDX6, N-cadherin, ß-catenin, Vimentin, Slug, Snail and Twist-1 through the activation of the PI3K/ AKT/p38/p50 pathways, but they were also significantly inhibited by PRDX6 transfectants. There was also increased transcriptional activation of dimethylation of histone H3 lysine 4 (H3K4me3) of PRDX6 promoter via the activation of the PI3K/Akt/NFkB pathways. CONCLUSION: Our findings demonstrated that PRDX6 expression plays a characteristic growth-promoting role in CRC metastasis. This study suggests that PRDX6 may serve as a biomarker of node-positive status and may have a role as an important endogenous regulator of cancer cell tumorigenicity in CRC. PRDX6 may also be an effective therapeutic target.

Observation of Effective Pseudospin Scattering in ZrSiS.

3D Dirac semimetals are an emerging class of materials that possess topological electronic states with a Dirac dispersion in their bulk. In nodal-line Dirac semimetals, the conductance and valence bands connect along a closed path in momentum space, leading to the prediction of pseudospin vortex rings and pseudospin skyrmions. Here, we use Fourier transform scanning tunneling spectroscopy (FT-STS) at 4.5 K to resolve quasiparticle interference (QPI) patterns at single defect centers on the surface of the line nodal semimetal zirconium silicon sulfide (ZrSiS). Our QPI measurements show pseudospin conservation at energies close to the line node. In addition, we determine the Fermi velocity to be ℏvF = 2.65 ± 0.10 eV Å in the Γ-M direction ∼300 meV above the Fermi energy EF and the line node to be ∼140 meV above EF. More importantly, we find that certain scatterers can introduce energy-dependent nonpreservation of pseudospin, giving rise to effective scattering between states with opposite pseudospin deep inside valence and conduction bands. Further investigations of quasiparticle interference at the atomic level will aid defect engineering at the synthesis level, needed for the development of lower-power electronics via dissipationless electronic transport in the future.

A proteomics approach to identifying novel protein targets involved in erinacine A-mediated inhibition of colorectal cancer cells' aggressiveness.

Erinacine A, a major active component of a diterpenoid derivative isolated from Hericium erinaceus mycelium, has been demonstrated to exert anticancer effects. Herein, we present an investigation of the molecular mechanism of erinacine A induction associated with cancer cells' aggressive status and death. A proteomic approach was used to purify and identify the differentially expressed proteins following erinacine A treatment and the mechanism of its action in apoptotic and the targets of erinacine A. Our results demonstrate that erinacine A treatment of HCT-116 and DLD-1 cells increased cell cytotoxicity and reactive oxygen species (ROS) production as well as decreased cell proliferation and invasiveness. Ten differentially displayed proteins were determined and validated in vitro and in vivo between the erinacine A-treated and untreated groups. In addition, erinacine A time-dependent induction of cell death and inhibitory invasiveness was associated with sustained phosphorylation of the PI3K/mTOR/p70S6K and ROCK1/LIMK2/Cofilin pathways. Furthermore, we demonstrated that erinacine A-induced HCT-116 and DLD-1 cells viability and anti-invasion properties by up-regulating the activation of PI3K/mTOR/p70S6K and production of ROS. Experiments involving specific inhibitors demonstrated that the differential expression of cofilin-1 (COFL1) and profilin-1 (PROF1) during erinacine A treatment could be involved in the mechanisms of HCT-116 and DLD-1 cells death and decreased aggressiveness, which occurred via ROCK1/LIMK2/Cofilin expression, with activation of the PI3K/mTOR/p70S6K signalling pathway. These findings elucidate the mechanism of erinacine A inhibiting the aggressive status of cells by activating PI3K/mTOR/p70S6K downstream signalling and the novel protein targets COF1 and PROF1; this could be a good molecular strategy to limit the aggressiveness of CRC cells.

A Comparative Proteomic Analysis of Erinacine A's Inhibition of Gastric Cancer Cell Viability and Invasiveness.

Background / Aims: Erinacine A, isolated from the ethanol extract of the Hericium erinaceus mycelium, has been demonstrated as a new alternative anticancer medicine. Drawing upon current research, this study presents an investigation of the molecular mechanism of erinacine A inhibition associated with gastric cancer cell growth. METHODS: Cell viability was determined by Annexin V-FITC/propidium iodide staining and migration using a Boyden chamber assay to determine the effects of erinacine A treatment on the proliferation capacity and invasiveness of gastric cancer cells. A proteomic assay provided information that was used to identify the differentially-expressed proteins following erinacine A treatment, as well as the mechanism of its targets in the apoptotic induction of erinacine A. RESULTS: Our results demonstrate that erinacine A treatment of TSGH 9201 cells increased cytotoxicity and the generation of reactive oxygen species (ROS), as well as decreased the invasiveness. Treatment of TSGH 9201 cells with erinacine A resulted in the activation of caspases and the expression of TRAIL. Erinacine A induction of apoptosis was accompanied by sustained phosphorylation of FAK/AKT/p70S6K and the PAK1 pathways, as well as the generation of ROS. Furthermore, the induction of apoptosis and anti-invasion properties by erinacine A could involve the differential expression of the 14-3-3 sigma protein (1433S) and microtubule-associated tumor suppressor candidate 2 (MTUS2), with the activation of the FAK/AKT/p70S6K and PAK1 signaling pathways. CONCLUSIONS: These results lead us to speculate that erinacine A may generate an apoptotic cascade in TSGH 9201 cells by activating the FAK/AKT/p70S6K/PAK1 pathway and upregulating proteins 1433S and MTUS2, providing a new mechanism underlying the anti-cancer effects of erinacine A in human gastric cancer cells.

Undergraduate nursing education to address patients' concerns about sexual health: the perceived learning needs of senior traditional four-year and two-year recurrent education (rn-bsn) undergraduate nursing students in taiwan.

The aims of this study were to identify learning needs among traditional four-year and two-year recurrent education (RN-BSN) undergraduate nursing students in Taiwan with regard to patients' concerns about sexual health. A 24-item instrument (Learning Needs for Addressing Patients' Sexual Health Concerns) was used to collect data. Compared to RN-BSN undergraduate nursing students, traditional four-year undergraduate nursing students had more learning needs in the aspects of sexuality in health and illness (2.19 ± 0.66 vs. 1.80 ± 0.89, P = 0.005) and approaches to sexual health care (2.03 ± 0.72 vs. 1.76 ± 0.86, P = 0.033). After adjustment for other variables by the backward selection approach, those with experience in assessing patient's sexual functioning had fewer learning needs in sexuality in health and illness (ß = -0.375, P = 0.001), communication about patient's intimate relationships (ß = -0.242, P = 0.031), and approaches to sexual health care (ß = -0.288, P = 0.013); those who agreed that sexual health care was a nursing role also expressed greater needs to learn about these 3 aspects (all P < 0.01). Content related to sexuality in health and illness and approaches to sexual health care should be strengthened in the traditional undergraduate nursing curriculum in order to support sexual health related competence, build a positive attitude regarding sexual health care as a nursing role, and strengthen the experience of assessing patient's sexual functioning. A different, simplified program may be more suitable for those with clinical experience.

The Cerebral Protective Effect of Novel Erinacines from Hericium erinaceus Mycelium on In Vivo Mild Traumatic Brain Injury Animal Model and Primary Mixed Glial Cells via Nrf2-Dependent Pathways.

Hericium erinaceus, a consumable mushroom, has shown a potential to enhance the production of neuroprotective bioactive metabolites. Traumatic brain injury (TBI) often leads to cognitive, physical, and psychosocial impairments, resulting in neuroinflammation and the loss of cortical neurons. In this research, the effects of H. erinaceus mycelium, its derivative erinacine C, along with the underlying mechanisms, were examined in terms of oxidative stress modulation and neurological improvement in a rat model of mild traumatic brain injury (mTBI). Male Sprague-Dawley rats were administered diets containing H. erinaceus mycelium and erinacine C following experimental brain injury; these supplements were continued throughout the recovery phase. The binding activity of NF-E2-related factor 2 (Nrf2) near antioxidant genes in mixed glial cells was measured by chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR). The motor beam walking test revealed that dietary supplementation of H. erinaceus mycelium resulted in modest improvements in spatial memory while inhibiting neuron cell death and microglial activation according to brain histological examination. These findings were further corroborated by the upregulation of several antioxidant enzymes (catalase, glutathione reductase, thioredoxin reductase, and superoxide dismutase) and phospho-CAMP-response element-binding (p-CREB) levels in the mTBI model treated with H. erinaceus mycelium. Erinacine C treatment led to significantly reduced brain inflammation and normalization of mTBI-induced deficits through the modulation of the Nrf2 activation pathway and upregulated expression of numerous Nrf2-binding antioxidant genes such as catalase, thioredoxin reductase, superoxide dismutase, and brain-derived neurotrophic factor. This study demonstrates the potential of H. erinaceus mycelium and erinacine C in facilitating recovery following mTBI, including the prevention of neuronal injury and inactivation of microglia through the Nrf2-mediated antioxidant pathway in vivo.

YPA: an integrated repository of promoter features in Saccharomyces cerevisiae.

This study presents the Yeast Promoter Atlas (YPA, http://ypa.ee.ncku.edu.tw/ or http://ypa.csbb.ntu.edu.tw/) database, which aims to collect comprehensive promoter features in Saccharomyces cerevisiae. YPA integrates nine kinds of promoter features including promoter sequences, genes' transcription boundaries-transcription start sites (TSSs), five prime untranslated regions (5'-UTRs) and three prime untranslated regions (3'UTRs), TATA boxes, transcription factor binding sites (TFBSs), nucleosome occupancy, DNA bendability, transcription factor (TF) binding, TF knockout expression and TF-TF physical interaction. YPA is designed to present data in a unified manner as many important observations are revealed only when these promoter features are considered altogether. For example, DNA rigidity can prevent nucleosome packaging, thereby making TFBSs in the rigid DNA regions more accessible to TFs. Integrating nucleosome occupancy, DNA bendability, TF binding, TF knockout expression and TFBS data helps to identify which TFBS is actually functional. In YPA, various promoter features can be accessed in a centralized and organized platform. Researchers can easily view if the TFBSs in an interested promoter are occupied by nucleosomes or located in a rigid DNA segment and know if the expression of the downstream gene responds to the knockout of the corresponding TFs. Compared to other established yeast promoter databases, YPA collects not only TFBSs but also many other promoter features to help biologists study transcriptional regulation.

Nursing students' attitudes towards provision of sexual health care in clinical practice.

AIMS AND OBJECTIVES: To investigate nursing students' attitudes towards providing sexual health care in clinical practice and to identify associated factors. BACKGROUND: Sexual health care is an important component of holistic health care. Nurses' personal sexual knowledge and attitudes are shown to influence provision of sexual health care. DESIGN: This is a descriptive, cross-sectional study. METHODS: We selected 146 senior nursing students by convenience sampling from nursing schools in two medical universities in central Taiwan. Data were collected using the Nursing Attitudes on Sexual Health Care scale developed based on the 'Permission/Limited Information/Specific Suggestions/Intensive Therapy' model. Higher scores indicated more positive attitudes. RESULTS: Participants' mean age was 22.15 years. Mean total Nursing Attitudes on Sexual Health Care scores ranged from 45-75 (61.40 ± 10.17). Nursing students' most positive attitudes towards Permission/Limited Information/Specific Suggestions/Intensive Therapy sexual healthcare interventions were at the Permission level, and least positive attitudes were at levels of Specific Suggestion and Intensive Therapy. The top three positive items were as follows: accept patients' expression of sexual concerns, initiate discussions and encourage patients to talk. Male nursing students had negative attitudes towards sexual healthcare interventions, which became more positive as age increased, especially at the Limited Information level. CONCLUSIONS: Nursing students had different attitudes towards different levels of sexual health care in the Permission/Limited Information/Specific Suggestions/Intensive Therapy model. Attitudes were associated with age and gender. The Nursing Attitudes on Sexual Health Care scale is useful and reliable for identifying nurses' attitudes towards providing sexual health care. RELEVANCE TO CLINICAL PRACTICE: The Permission/Limited Information/Specific Suggestions/Intensive Therapy-based Nursing Attitudes on Sexual Health Care scale helps to identify nurses' attitudes. A better understanding of nurses' attitudes towards provisional sexual health care will provide information needed to develop appropriate education programmes to improve delivery of sexual health care.