Increased prevalence but decreased survival of nonviral hepatocellular carcinoma compared to viral hepatocellular carcinoma in recent ten years.

Due to the comprehensive hepatitis B virus vaccination program in Taiwan since 1986, the development of antiviral therapy for chronic hepatitis B and chronic hepatitis C infection and covered by National health insurance. Besides, the increased prevalence of nonalcoholic fatty liver disease (NAFLD) and currently, approved therapy for NAFLD remain developing. The etiology of liver-related diseases such as cirrhosis and hepatocellular carcinoma required reinterpretation. This study aimed to analyze the incidence and outcome of hepatocellular carcinoma (HCC) due to viral (hepatitis B and hepatitis C) infection compared to that of nonviral etiology. We retrospectively analyzed patients with HCC from January 2011 to December 2020 from the cancer registry at our institution. Viral-related hepatitis was defined as hepatitis B surface antigen positivity or anti-hepatitis C virus (HCV) antibody positivity. A total of 2748 patients with HCC were enrolled, of which 2188 had viral-related HCC and 560 had nonviral-related HCC. In viral HCC group, the median age at diagnosis was significantly lower (65 years versus 71 years, p < 0.001), and the prevalence of early-stage HCC, including stage 0 and stage A Barcelona Clinic Liver Cancer, was significantly higher (52.9% versus 33.6%, p < 0.001). In nonviral HCC group, alcohol use was more common (39.9% versus 30.1%, p < 0.001), the prevalence of type 2 diabetes mellitus (T2DM) was higher (54.5% versus 35.1%, p < 0.001), and obesity was common (25.0% versus 20.5%, p = 0.026). The prevalence of nonviral HCC increased significantly from 19.2 to 19.3% and 23.0% in the last 10 years (p = 0.046). Overall survival was better in the viral HCC group (5.95 years versus 4.00 years, p < 0.001). In the early stage of HCC, overall survival was still better in the viral HCC group (p < 0.001). The prevalence of nonviral HCC has significantly increased in the last ten years. The overall survival was significantly lower in the nonviral HCC, perhaps because the rate of early HCC detection is lower in nonviral HCC and anti-viral therapy. To detect nonviral HCC early, we should evaluate liver fibrosis in high-risk groups (including people with obesity or T2DM with NAFLD/NASH and alcoholic liver disease) and regular follow-up for those with liver fibrosis, regardless of cirrhosis.

A hierarchical fusion strategy of deep learning networks for detection and segmentation of hepatocellular carcinoma from computed tomography images.

BACKGROUND: Automatic segmentation of hepatocellular carcinoma (HCC) on computed tomography (CT) scans is in urgent need to assist diagnosis and radiomics analysis. The aim of this study is to develop a deep learning based network to detect HCC from dynamic CT images. METHODS: Dynamic CT images of 595 patients with HCC were used. Tumors in dynamic CT images were labeled by radiologists. Patients were randomly divided into training, validation and test sets in a ratio of 5:2:3, respectively. We developed a hierarchical fusion strategy of deep learning networks (HFS-Net). Global dice, sensitivity, precision and F1-score were used to measure performance of the HFS-Net model. RESULTS: The 2D DenseU-Net using dynamic CT images was more effective for segmenting small tumors, whereas the 2D U-Net using portal venous phase images was more effective for segmenting large tumors. The HFS-Net model performed better, compared with the single-strategy deep learning models in segmenting small and large tumors. In the test set, the HFS-Net model achieved good performance in identifying HCC on dynamic CT images with global dice of 82.8%. The overall sensitivity, precision and F1-score were 84.3%, 75.5% and 79.6% per slice, respectively, and 92.2%, 93.2% and 92.7% per patient, respectively. The sensitivity in tumors < 2 cm, 2-3, 3-5 cm and > 5 cm were 72.7%, 92.9%, 94.2% and 100% per patient, respectively. CONCLUSIONS: The HFS-Net model achieved good performance in the detection and segmentation of HCC from dynamic CT images, which may support radiologic diagnosis and facilitate automatic radiomics analysis.

Metabolic Dysfunction-Associated Fatty Liver Disease in Taiwanese Patients with Inflammatory Bowel Disease: A Study in Patients with Clinical Remission.

The prevalence of inflammatory bowel disease (IBD) has increased worldwide. The prevalence of metabolic dysfunction associated fatty liver disease (MAFLD) has also risen. However, there is limited research on the connection between MAFLD and IBD in the Asian population. This study aims to analyze the prevalence and clinical significance of MAFLD in Taiwanese IBD patients with clinical remission. We retrospectively analyzed IBD patients who received transient elastography for liver fibrosis and controlled attenuation parameter evaluation for liver steatosis. This study enrolled 120 patients with IBD, including 45 Crohn's disease (CD) and 75 ulcerative colitis (UC). MAFLD prevalence in IBD was 29.2%. Patients with MAFLD had a shorter disease duration (2.8 years vs. 5.3 years, p = 0.017), higher alanine aminotransferase levels (24 U/L vs. 17 U/L, p = 0.003), a lower estimated glomerular filtration rate (91.37 mL/min/1.73 m2 vs. 103.92 mL/min/1.73 m2, p = 0.004), and higher γ-glutamyl transferase (γ-GT) (24 mg/dL vs. 13 mg/dL, p < 0.001). The prevalence of significant fibrosis in IBD with MAFLD was 17.1%. Significant fibrosis was found in older age (58.5 years vs. 40 years, p = 0.004) and the high type 2 diabetes mellitus proportion (50.0% vs. 10.3%, p = 0.049). A trend of longer disease duration was found in significant fibrosis (4.9 years vs. 1.6 years, p = 0.051). The prevalence of MALFD in IBD was 29.2%. and 17.1% of them had significant fibrosis. In addition to the intestinal manifestation, the study findings remind clinicians that they should be aware of the possibility of hepatic complications for IBD patients.

Refined Techniques for Enabling Long-Term Cryo-Repository Using Vitrification and Laser Warming.

Vitrification and ultrarapid laser warming are crucial for the cryopreservation of animal embryos, oocytes, and other cells of medicinal, genetic, and agricultural value. In the present study, we focused on alignment and bonding techniques for a special cryojig that combines a jig tool and jig holder into one piece. This novel cryojig was used to obtain a high laser accuracy of 95% and a successful rewarming rate of 62%. The experimental results indicated that our refined device improved laser accuracy in the warming process after long-term cryo-storage through vitrification. We anticipate that our findings will lead to cryobanking applications that use vitrification and laser nanowarming to preserve cells and tissues from a wide range of species.

Four Sessions of Combining Wearable Devices and Heart Rate Variability (HRV) Biofeedback are Needed to Increase HRV Indices and Decrease Breathing Rates.

Heart rate variability biofeedback (HRVB) is a behavioral intervention that uses resonance frequency breathing to synchronize the heart rate and breathing patterns. This study aimed to explore how many sessions of wearable HRVB devices are needed to increase the HRV index and decrease breathing rates and to compare the HRVB protocol with other psychological intervention programs in HRV indices and breathing rates. Sixty-four participants were randomly assigned to either the HRVB or relaxation training (RT) group. Both groups received interbeat intervals (IBIs) and breathing rates measurement at the pre-training baseline, during training, and post-training baseline from weeks 1 to 4. IBIs were transformed into HRV indices as the index of the autonomic nervous system. The Group × Week interaction effects significantly in HRV indices and breathing rates. The between-group comparison found a significant increase in HRV indices and decreased breathing rates in the HRVB group than in the RT group at week 4. The within-session comparison in the HRVB group revealed significantly increased HRV indices and decreased breathing rates at weeks 3 and 4 than at weeks 1 and 2. There was a significant increase in HRV indices and a decrease in breathing rates at mid- and post-training than pre-training in the HRVB group. Therefore, 4 weeks of HRVB combined with a wearable device are needed in increasing HRV indices and decrease breathing rates compared to the relaxation training. Three weeks of HRVB training are the minimum requirement for increasing HRV indices and reducing breathing rates compared to the first week of HRVB.

Validation of the modified Chinese Information and Support Needs Questionnaire (ISNQ-C) for daughters of mothers with breast cancer.

BACKGROUND: Adult daughters concerned about getting breast cancer throughout their lives and required support because their mothers had breast cancer. OBJECTIVES: This article aims to examine the revised Information and Support Needs Questionnaire (ISNQ) and validate it in a Taiwanese community population comprising daughters of mothers with breast cancer. METHODS: Using convenience sampling, daughters of mothers with breast cancer were recruited and were separated into 2 samples (Sample 1, n = 102, and Sample 2, n = 118). First, we translated and modified the ISNQ to ensure cultural adaptation and formed ISNQ Chinese version (ISNQ-C). Second, we conducted an exploratory factor analysis using both samples to explore the ISNQ-C factor structure. Finally, we tested the criterion validity and known-group validity of the ISNQ-C using Sample 2. RESULTS: Thirty-two items addressing 5 factors were identified for the ISNQ-C. Each factor had good internal consistency. The criterion validity was supported by significant correlations between the ISNQ-C scores and scores on the impacts of an event, anxiety, and depression. Known-group comparisons revealed that the group with deceased mothers reported significantly more unmet needs related to "releasing my anxiety" compared to the group where the mother was stable and undergoing regular follow-ups. SIGNIFICANCE OF RESULTS: The ISNQ-C demonstrated good reliability and validity in terms of assessing needs among daughters of mothers with breast cancer in Taiwan. Using this assessment tool before genetic counseling to target the individual needs of this population at risk for breast cancer would be helpful to provide personalized care.

Erinacine A Prevents Lipopolysaccharide-Mediated Glial Cell Activation to Protect Dopaminergic Neurons against Inflammatory Factor-Induced Cell Death In Vitro and In Vivo.

Hericium erinaceus (HE) is a common edible mushroom consumed in several Asian countries and considered to be a medicinal mushroom with neuroprotective effects. Erinacine A (EA) is a bioactive compound in Hericium erinaceus mycelium (HEM) that has been shown to have a neuroprotective effect against neurodegenerative diseases, e.g., Parkinson's disease (PD). Although the etiology of PD is still unclear, neuroinflammation may play an important role in causing dopaminergic neuron loss, which is a pathological hallmark of PD. However, glial cell activation has a close relationship with neuroinflammation. Thus, this study aimed to investigate the anti-neuroinflammatory and neuroprotective effects of EA on lipopolysaccharide (LPS)-induced glial cell activation and neural damage in vitro and in vivo. For the in vitro experiments, glial cells, BV-2 microglial cells and CTX TNA2 astrocytes were pretreated with EA and then stimulated with LPS and/or IFN-γ. The expression of proinflammatory factors in the cells and culture medium was analyzed. In addition, differentiated neuro-2a (N2a) cells were pretreated with EA or HEM and then stimulated with LPS-treated BV-2 conditioned medium (CM). The cell viability and the amount of tyrosine hydroxylase (TH) and mitogen-activated protein kinases (MAPKs) were analyzed. In vivo, rats were given EA or HEM by oral gavage prior to injection of LPS into the substantia nigra (SN). Motor coordination of the rats and the expression of proinflammatory mediators in the midbrain were analyzed. EA pretreatment prevented LPS-induced iNOS expression and NO production in BV-2 cells and TNF-α expression in CTX TNA2 cells. In addition, both EA and HEM pretreatment significantly increased cell viability and TH expression and suppressed the phosphorylation of JNK and NF- κB in differentiated N2a cells treated with CM. In vivo, both EA and HEM significantly improved motor dysfunction in the rotarod test and the amphetamine-induced rotation test and reduced the expression of TNF-α, IL-1ß and iNOS in the midbrain of rats intranigrally injected with LPS. The results demonstrate that EA ameliorates LPS-induced neuroinflammation and has neuroprotective properties.

Evolutionary Learning-Derived Clinical-Radiomic Models for Predicting Early Recurrence of Hepatocellular Carcinoma after Resection.

BACKGROUND AND AIMS: Current prediction models for early recurrence of hepatocellular carcinoma (HCC) after surgical resection remain unsatisfactory. The aim of this study was to develop evolutionary learning-derived prediction models with interpretability using both clinical and radiomic features to predict early recurrence of HCC after surgical resection. METHODS: Consecutive 517 HCC patients receiving surgical resection with available contrast-enhanced computed tomography (CECT) images before resection were retrospectively enrolled. Patients were randomly assigned to a training set (n = 362) and a test set (n = 155) in a ratio of 7:3. Tumor segmentation of all CECT images including noncontrast phase, arterial phase, and portal venous phase was manually performed for radiomic feature extraction. A novel evolutionary learning-derived method called genetic algorithm for predicting recurrence after surgery of liver cancer (GARSL) was proposed to design prediction models for early recurrence of HCC within 2 years after surgery. RESULTS: A total of 143 features, including 26 preoperative clinical features, 5 postoperative pathological features, and 112 radiomic features were used to develop GARSL preoperative and postoperative models. The area under the receiver operating characteristic curves (AUCs) for early recurrence of HCC within 2 years were 0.781 and 0.767, respectively, in the training set, and 0.739 and 0.741, respectively, in the test set. The accuracy of GARSL models derived from the evolutionary learning method was significantly better than models derived from other well-known machine learning methods or the early recurrence after surgery for liver tumor (ERASL) preoperative (AUC = 0.687, p < 0.001 vs. GARSL preoperative) and ERASL postoperative (AUC = 0.688, p < 0.001 vs. GARSL postoperative) models using clinical features only. CONCLUSION: The GARSL models using both clinical and radiomic features significantly improved the accuracy to predict early recurrence of HCC after surgical resection, which was significantly better than other well-known machine learning-derived models and currently available clinical models.

Electroencephalogram patterns in patients comorbid with major depressive disorder and anxiety symptoms: Proposing a hypothesis based on hypercortical arousal and not frontal or parietal alpha asymmetry.

BACKGROUND: Major depressive disorder (MDD) is often comorbid with anxiety disorders or symptoms. Brain hyperactivity, frontal alpha asymmetry (FAA), and parietal alpha asymmetry (PAA) have been considered as trait markers in patients with MDD. This study investigated the electroencephalogram (EEG) patterns among patients with MDD comorbid with anxiety symptoms. METHODS: One hundred and thirty-five patients with MDD comorbid with anxiety (MDD group) and 135 healthy controls (HC group) were analyzed. The Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI) were completed, and 19 EEG channels were measured during the resting state, depressive recall and recovery tasks, and happiness recall and recovery tasks. FAA and PAA were computed by log (F4 alpha)-log (F3 alpha) and log (P4 alpha)-log (P3 alpha). RESULTS: The FAA and PAA indices between the two groups showed no significant differences; however, compared with the HC group, the MDD group had lower total delta and theta values, and higher total beta, low beta, and high beta values in the resting state. The total beta value positively correlated with the BDI-II and BAI scores in the MDD group. LIMITATIONS: Most patients had anxious MDD and taking prescriptions, antidepressants or benzodiazepine may affect EEG patterns. CONCLUSION: Compared with HCs, patients with MDD comorbid with anxiety had a higher beta activity in the entire brain region, supporting the role of brain hyperactivity, instead of FAA or PAA, as a trait marker in these patients. A neurofeedback protocol could be developed in future based on the brain hyperactivity findings.

Selection of a malignant subpopulation from a colorectal cancer cell line.

Colorectal cancer (CRC) is a leading cause of cancer-associated mortality worldwide; therefore, there is an emerging need for novel experimental models that allow for the identification and validation of biomarkers for CRC-specific progression. In the present study, a repeated sphere-forming assay was used as a strategy to select a malignant subpopulation from a CRC cell line, namely HCT116. The assay was validated by confirming that canonical stemness markers were upregulated in the sphere state at every generation of the selection assay. The resulting subpopulation, after eight rounds of selection, exhibited increased sphere-forming capacity in vitro and increased tumorigenicity in vivo. Furthermore, dipeptidase 1 (DPEP1) was identified as the major differentially expressed gene in the selected clone, and its depletion suppressed the elevated sphere-forming capacity in vitro and tumorigenicity in vivo. Overall, the present study established an experimental strategy to isolate a malignant subpopulation from a CRC cell line. Additionally, results from the present model revealed that DPEP1 may serve as a promising prognostic biomarker for CRC.

The learning effects and curves during high beta down-training neurofeedback for patients with major depressive disorder.

BACKGROUND: Electroencephalography (EEG) has revealed increased beta activity in patients with comorbid major depressive disorder (MDD) and anxiety symptoms. Negative emotions and high beta activity could be decreased by a high beta down-training neurofeedback (NFB) protocol. The present study utilized three objective parameters - trainability, independence, and interpretability - to validate the effects of high beta down-training sessions. METHODS: EEG data were collected from 23 patients with comorbid MDD and anxiety symptoms during high beta down-training sessions. Participants received five weeks of training, two sessions per week, to down-train high beta amplitude (20-32 Hz) at EEG sites P3 and P4. Three efficacy parameters were examined by comparing pre-training and post-training EEG. RESULTS: The trainability index revealed the learning curves of reduced high beta activity at P3 and P4, confirming training effects across and within sessions. The independence index revealed only beta band activity decreased. The interpretability index revealed the decreased high beta activity was positively correlated with decreased severity of depression, especially for cognitive depression. LIMITATIONS: With only ten sessions in this study, it is unknown whether the NFB training caused extended and stable learning effects. Additionally, combining high beta down-training protocol with enhancing another target band could better ensure the desired changes in brain activity. Finally, the effect of medication on EEG cannot be excluded in present study. CONCLUSIONS: The trainability, independence and interpretability of the high beta down-training NFB protocol were confirmed, supporting the protocol's use in future research and clinical applications.

Peptide inhibitors of the anaphase promoting-complex that cause sensitivity to microtubule poison.

There is an interest in identifying Anaphase Promoting-Complex/Cyclosome (APC/C) inhibitors that lead to sensitivity to microtubule poisons as a strategy for targeting cancer cells. Using budding yeast Saccharomyces cerevisiae, peptides derived from the Mitotic Arrest Deficient 2 (Mad2)-binding motif of Cell Division Cycle 20 (Cdc20) were observed to inhibit both Cdc20- and CDC20 Homology 1 (Cdh1)-dependent APC/C activity. Over expression of peptides in vivo led to sensitivity to a microtubule poison and, in a recovery from a microtubule poison arrest, delayed degradation of yeast Securin protein Precocious Dissociation of Sisters 1 (Pds1). Peptides with mutations in the Cdc20 activating KILR-motif still bound APC/C, but lost the ability to inhibit APC/C in vitro and lost the ability to induce sensitivity to a microtubule poison in vivo. Thus, an APC/C binding and activation motif that promotes mitotic progression, namely the Cdc20 KILR-motif, can also function as an APC/C inhibitor when present in excess. Another activator for mitotic progression after recovery from microtubule poison is p31comet, where a yeast predicted open-reading frame YBR296C-A encoding a 39 amino acid predicted protein was identified by homology to p31comet, and named Tiny Yeast Comet 1 (TYC1). Tyc1 over expression resulted in sensitivity to microtubule poison. Tyc1 inhibited both APC/CCdc20 and APC/CCdh1 activities in vitro and bound to APC/C. A homologous peptide derived from human p31comet bound to and inhibited yeast APC/C demonstrating evolutionary retention of these biochemical activities. Cdc20 Mad2-binding motif peptides and Tyc1 disrupted the ability of the co-factors Cdc20 and Cdh1 to bind to APC/C, and co-over expression of both together in vivo resulted in an increased sensitivity to microtubule poison. We hypothesize that Cdc20 Mad2-binding motif peptides, Tyc1 and human hp31 peptide can serve as novel molecular tools for investigating APC/C inhibition that leads to sensitivity to microtubule poison in vivo.

NPFFR2 Activates the HPA Axis and Induces Anxiogenic Effects in Rodents.

Neuropeptide FF (NPFF) belongs to the RFamide family and is known as a morphine-modulating peptide. NPFF regulates various hypothalamic functions through two receptors, NPFFR1 and NPFFR2. The hypothalamic-pituitary-adrenal (HPA) axis participates in physiological stress response by increasing circulating glucocorticoid levels and modulating emotional responses. Other RFamide peptides, including neuropeptide AF, neuropeptide SF and RFamide related peptide also target NPFFR1 or NPFFR2, and have been reported to activate the HPA axis and induce anxiety- or depression-like behaviors. However, little is known about the action of NPFF on HPA axis activity and anxiety-like behaviors, and the role of the individual receptors remains unclear. In this study, NPFFR2 agonists were used to examine the role of NPFFR2 in activating the HPA axis in rodents. Administration of NPFFR2 agonists, dNPA (intracerebroventricular, ICV) and AC-263093 (intraperitoneal, IP), time-dependently (in rats) and dose-dependently (in mice) increased serum corticosteroid levels and the effects were counteracted by the NPFF receptor antagonist, RF9 (ICV), as well as corticotropin-releasing factor (CRF) antagonist, α-helical CRF(9-41) (intravenous, IV). Treatment with NPFFR2 agonist (AC-263093, IP) increased c-Fos protein expression in the hypothalamic paraventricular nucleus and induced an anxiogenic effect, which was evaluated in mice using an elevated plus maze. These findings reveal, for the first time, that the direct action of hypothalamic NPFFR2 stimulates the HPA axis and triggers anxiety-like behaviors.

Relationship Between Predictors of Incident Deliberate Self-Harm and Suicide Attempts Among Adolescents.

PURPOSE: Data on the incidence of deliberate self-harm (DSH) and suicide attempts (SAs) are lacking in non-Western adolescents, and no studies have investigated differences in incident DSH and SA worldwide. This study aimed to investigate the incidence rates and relationships between predictors in DSH and SA. METHODS: The Taiwanese Adolescent Self-Harm Project was a longitudinal study of DSH among adolescents. We recruited 5,879 students from 14 senior high schools in northern Taiwan. Online questionnaires on sociodemographic data, suicidality, depressive symptoms, self-esteem, social support, family discord, impulsivity, and alcohol and tobacco use were assessed at baseline (T1) and at 1 year of follow-up (T2). Logistic regression analyses were performed to evaluate the predictors of incident DSH and SA. RESULTS: The mean age was 16.02 years, and 56.73% of the cohort was female. At T1, the lifetime prevalence rates of DSH and SA were 25.04% and 3.50%, respectively. At T2, 4,331 (73.67%) students had completed follow-up assessments. The 1-year incidence rates of DSH and SA were 4.04% and 1.53%, respectively. The predictors of incident DSH included perceived family discord and more depressive symptoms at T1. The predictors of incident SA were lifetime suicide ideation, more depressive symptoms, and tobacco use at T1. CONCLUSIONS: The incidence rates of DSH and SA were similar to those reported in Western countries. The predictors of incident DSH and SA were similar but not identical. Our results highlight the risk factors which should be considered in terms of early identification and intervention among adolescents to prevent suicidality.

Relationship between Sugar Intake and Obesity among School-Age Children in Kaohsiung, Taiwan.

In recent years, the prevalence and problem of overweight and obesity in Taiwanese children have increased. There are many reports that the excessive intake of sugar increases the risk of lifestyle-related disease. However, sugar intake in Taiwanese children is not known. In this study, we investigated sugar intake from sugar-sweetened beverages, snacks and desserts among school-age children in Kaohsiung, Taiwan. We also tried to determine the relationship between sugar intake and body mass index (BMI). We contacted all the public elementary schools (10 schools) in a district, Kaohsiung, and obtained permission from 3 schools. The survey subjects were 410 (210 boys, 200 girls) school-age children (7, 10 and 12 y old). A nutrition survey was conducted using 3 non-consecutive days of the 24 h dietary recall method for sugar-sweetened beverages, snacks and desserts. Height and weight were measured. Sugar intakes were not significantly different among the different genders or ages (p>0.05) and average intake of all was 51.6 g/d. Percentages of each sugar in total intake were sucrose 60%, glucose 18%, fructose 16%, and lactose 6%. The intake of glucose and fructose may have come from isomerized sugar. Contributions of sugar-sweetened beverages and snacks (desserts) were 83.5% and 16.5%, respectively. Among the sugar-sweetened beverages the top 3 sources were tea (22%), milk tea (19%) and milk beverages (18%). A relationship between sugar intake and BMI was not observed. In conclusion, sugar intake of the children was higher than the WHO recommendation due to the high intake from beverages; however, sugar was not the cause of the high obesity rate.

Chronic activation of NPFFR2 stimulates the stress-related depressive behaviors through HPA axis modulation.

Neuropeptide FF (NPFF) is a morphine-modulating peptide that regulates the analgesic effect of opioids, and also controls food consumption and cardiovascular function through its interaction with two cognate receptors, NPFFR1 and NPFFR2. In the present study, we explore a novel modulatory role for NPFF-NPFFR2 in stress-related depressive behaviors. In a mouse model of chronic mild stress (CMS)-induced depression, the expression of NPFF significantly increased in the hypothalamus, hippocampus, medial prefrontal cortex (mPFC) and amygdala. In addition, transgenic (Tg) mice over-expressing NPFFR2 displayed clear depression and anxiety-like behaviors with hyperactivity in the hypothalamic-pituitary-adrenal (HPA) axis, reduced expression of glucocorticoid receptor (GR) and neurogenesis in the hippocampus. Furthermore, acute treatment of NPFFR2 agonists in wild-type (WT) mice enhanced the activity of the HPA axis, and chronic administration resulted in depressive and anxiety-like behaviors. Chronic stimulation of NPFFR2 also decreased the expression of hippocampal GR and led to persistent activation of the HPA axis. Strikingly, bilateral intra-paraventricular nucleus (PVN) injection of NPFFR2 shRNA predominately inhibits the depressive-like behavior in CMS-exposed mice. Antidepressants, fluoxetine and ketamine, effectively relieved the depressive behaviors of NPFFR2-Tg mice. We speculate that persistent NPFFR2 activation, in particular in the hypothalamus, up-regulates the HPA axis and results in long-lasting increases in circulating corticosterone (CORT), consequently damaging hippocampal function. This novel role of NPFFR2 in regulating the HPA axis and hippocampal function provides a new avenue for combating depression and anxiety-like disorder.

Genomic and transcriptomic analyses of the medicinal fungus Antrodia cinnamomea for its metabolite biosynthesis and sexual development.

Antrodia cinnamomea, a polyporus mushroom of Taiwan, has long been used as a remedy for cancer, hypertension, and hangover, with an annual market of over $100 million (US) in Taiwan. We obtained a 32.15-Mb genome draft containing 9,254 genes. Genome ontology enrichment and pathway analyses shed light on sexual development and the biosynthesis of sesquiterpenoids, triterpenoids, ergostanes, antroquinonol, and antrocamphin. We identified genes differentially expressed between mycelium and fruiting body and 242 proteins in the mevalonate pathway, terpenoid pathways, cytochrome P450s, and polyketide synthases, which may contribute to the production of medicinal secondary metabolites. Genes of secondary metabolite biosynthetic pathways showed expression enrichment for tissue-specific compounds, including 14-α-demethylase (CYP51F1) in fruiting body for converting lanostane to ergostane triterpenoids, coenzymes Q (COQ) for antroquinonol biosynthesis in mycelium, and polyketide synthase for antrocamphin biosynthesis in fruiting body. Our data will be useful for developing a strategy to increase the production of useful metabolites.

A communication platform for diabetes surveillance.

Diabetes mellitus is a common and precarious chronic disease, which affects cellular metabolism and energy production. The condition is divided into types I and II; the most common form is type II diabetes, which is an adult-onset disease. Blood glucose testing is crucial to diabetes control, and it is effective in reducing the risk of complications and improving life quality. Unfortunately, both elderly patients and their caregivers find it difficult to monitor glucose levels long term. This study developed a communication platform for diabetes surveillance. The developed system prompts diabetics to measure their blood glucose regularly at home, and provides remote care persons with complete information about the patient's measurement. This aids in the improvement in diabetes control, thereby increasing the social activities and life quality of diabetics.