Oral administration of osthole mitigates maladaptive behaviors through PPARα activation in mice subjected to repeated social defeat stress.

Psychological stress induces neuroinflammatory responses, which are associated with the pathogenesis of various psychiatric disorders, such as posttraumatic stress disorder and anxiety. Osthole-a natural coumarin isolated from the seeds of the Chinese herb Cnidium monnieri-exerts anti-inflammatory and antioxidative effects on the central nervous system. However, the therapeutic benefits of osthole against psychiatric disorders remain largely unknown. We previously demonstrated that mice subjected to repeated social defeat stress (RSDS) in the presence of aggressor mice exhibited symptoms of posttraumatic stress disorder, such as social avoidance and anxiety-like behaviors. In this study, we investigated the therapeutic effects of osthole and the underlying molecular mechanisms. Osthole exerted therapeutic effects on cognitive behaviors, mitigating anxiety-like behaviors and social avoidance in a mouse model of RSDS. The anti-inflammatory response induced by the oral administration of osthole was strengthened through the upregulation of heme oxygenase-1 expression. The expression of PPARα was inhibited in mice subjected to RSDS. Nonetheless, osthole treatment reversed the inhibition of PPARα expression. We identified a positive correlation between heme oxygenase-1 expression and PPARα expression in osthole-treated mice. In conclusion, osthole has potential as a Chinese herbal medicine for anxiety disorders. When designing novel drugs for psychiatric disorders, researchers should consider targeting the activation of PPARα.

Perinatal maternal factors influencing postpartum feeding practices at six weeks.

OBJECTIVE: Despite the World Health Organization's recommendation of exclusive breastfeeding for the initial 6 months, breastfeeding rates decline within the first 6 weeks after delivery. This study aimed to (1) investigate the breastfeeding rate at 6 weeks postpartum and (2) explore the influence of perinatal factors on feeding patterns at 6 weeks postpartum. METHOD: A total of 635 participants were enrolled from February to August 2023 at outpatient clinics in three tertiary hospitals in Nantong City. Variables were collected through questionnaires during the third trimester of pregnancy, including demographic information, pregnancy stress, anxiety, depression, sleep, and resilience. At 6 weeks postpartum, information regarding feeding patterns, delivery and postpartum situations, postpartum stress, anxiety, depression, sleep, and resilience was gathered. Initial single-factor analyses were conducted using feeding pattern as the dependent variable, and variables with significance were chosen as independent variables. The disordered multi-classification logistic regression model was then established using the stepwise forward method. RESULTS: Within the first 6 weeks, 35.28% (224/635) of postpartum women exclusively breastfed their infants. Factors influencing exclusive breastfeeding and formula feeding at 6 weeks postpartum included breast pain, sleep quality, mental resilience, difference between postpartum and late pregnancy anxiety, insufficient milk supply, and maternal herself caring for the infant (P < 0.05). Factors influencing the transition from exclusive to partial breastfeeding were insufficient milk supply and maternal herself caring for the infant (P < 0.05). CONCLUSION: The study reveals a relative low rate of exclusive breastfeeding in China's first 6 weeks postpartum, along with a comparison of perinatal factors affecting three different feeding patterns. Our findings may contribute additional evidence to the association between perinatal factors and feeding patterns. This study guides healthcare professionals in developing strategies to promote exclusive breastfeeding and improve personalized counseling for exclusive breastfeeding and mental health.

AN698/40746067 suppresses bone marrow adiposity to ameliorate hyperlipidemia-induced osteoporosis through targeted inhibition of ENTR1.

Hyperlipidemia-induced osteoporosis is marked by increased bone marrow adiposity, and treatment with statins for hyperlipidemia often leads to new-onset osteoporosis. Endosome-associated trafficking regulator 1 (ENTR1) has been found to interact with different proteins in pathophysiology, but its exact role in adipogenesis is not yet understood. This research aimed to explore the role of ENTR1 in adipogenesis and to discover a new small molecule that targets ENTR1 for evaluating its effectiveness in treating hyperlipidemia-induced osteoporosis. We found that ENTR1 expression increased during the adipogenesis of bone marrow mesenchymal cells (BMSCs). ENTR1 gain- and loss-of-function assays significantly enhanced lipid droplets formation. Mechanistically, ENTR1 binds peroxisome proliferator-activated receptor γ (PPARγ) and enhances its expression, thereby elevating adipogenic markers including C/EBPα and LDLR. Therapeutically, AN698/40746067 attenuated adipogenesis by targeting ENTR1 to suppress PPARγ. In vivo, AN698/40746067 reduced bone marrow adiposity and bone loss, as well as prevented lipogenesis-related obesity, inflammation, steatohepatitis, and abnormal serum lipid levels during hyperlipidemia. Together, these findings suggest that ENTR1 facilitates adipogenesis by PPARγ involved in BMSCs' differentiation, and targeted inhibition of ENTR1 by AN698/40746067 may offer a promising therapy for addressing lipogenesis-related challenges and alleviating osteoporosis following hyperlipidemia.

Advances in systemic immune inflammatory indices in non-small cell lung cancer: A review.

Lung cancer is one of the most prevalent cancers globally, with non-small cell lung cancers constituting the majority. These cancers have a high incidence and mortality rate. In recent years, a growing body of research has demonstrated the intricate link between inflammation and cancer, highlighting that inflammation and cancer are inextricably linked and that inflammation plays a pivotal role in cancer development, progression, and prognosis of cancer. The Systemic Immunoinflammatory Index (SII), comprising neutrophil, lymphocyte, and platelet counts, is a more comprehensive indicator of the host's systemic inflammation and immune status than a single inflammatory index. It is widely used in clinical practice due to its cost-effectiveness, simplicity, noninvasiveness, and ease of acquisition. This paper reviews the impact of SII on the development, progression, and prognosis of non-small cell lung cancer.

Ethnobotanical Knowledge, Nutritional Composition, and Aroma Profile of Vicia kulingiana Bailey: An Underutilized Wild Vegetable Endemic to China.

Vicia kulingiana, an endemic species, serves as a wild and underutilized vegetable traditionally consumed in China. However, ethnobotanical and chemical studies of this species are not available. This study analyzed its associated ethnobotanical knowledge, nutritional composition and aroma profile. Ethnobotanical surveys revealed its diverse traditional uses, especially as a nutritious vegetable. Further analysis showed V. kulingiana leaves to be high in protein, minerals, vitamin E, and dietary fiber. In total, 165 volatile compounds, such as terpenoids, alcohols, and ketones, were identified. Among them, ß-ionone is the most abundant compound with a relative percentage of 8.24%, followed by 2,2,4,6,6-pentamethylheptane (3.2%), 3-(4-methyl-3-pentenyl)furan (2.37%), and linalool (1.68%). Results supported the traditional uses of V. kulingiana's and highlighted its potential as a valuable food source, encouraging further research on its food applications. The documentation of ethnobotanical knowledge contributes to the conservation of this heritage.

The short-term outcome of intracranial stenosis with distal thrombosis treated with balloon-assisted tracking.

Background and purposes: Treating intracranial stenosis with distal thrombosis (IS&DT) using traditional mechanical thrombectomy (MT) techniques has proven challenging. This study aimed to summarize the experience of utilizing the balloon-assisted tracking (BAT) technique for IS&DT. Methods: Demographic and morphologic characteristics of patients with IS&DT were collected for this study. The BAT technique, involving a half-deflated balloon outside the intermediate catheter tip, was used in all patients to navigate through the proximal stenosis. Various parameters were recorded, including the sequence of vascular reperfusion, the puncture-to-reperfusion time (PRT), the residual stenosis rate, and the occurrence of re-occlusion. The thrombolysis in cerebral infarction (TICI) scale was used to assess the reperfusion of intracranial vessels, with a TICI score of ≥2b considered as successful perfusion. The clinical status of patients was evaluated at three time points: pre-procedure, post-procedure, and at discharge using the modified Rankin score (mRS). Results: In this study, a total of 10 patients were diagnosed with IS&DT, consisting of 9 male patients (90.0%) and 1 female patient (10.0%). The patients' mean age was 63.10 years (ranging from 29 to 79 years). The mean National Institute of Health Stroke Scale (NIHSS) score before treatment was 24.3 (ranging from 12 to 40), indicating the severity of their condition. Following the procedure, all patients achieved successful reperfusion with a thrombolysis in cerebral infarction (TICI) score of ≥2b. The average puncture-to-reperfusion time (PRT) was 51.8 min (ranging from 25 to 100 min), indicating the time taken for the procedure. During the perioperative period, three patients (30.0%) experienced complications. One patient had hemorrhage, while two patients had contrast extravasation. Among these cases, only the patient with hemorrhage (10%) suffered from a permanent neurological function deficit. At discharge, the patient's condition showed improvement. The mean NIHSS score decreased to 13.2 (ranging from 1 to 34), indicating a positive response to treatment. The mean mRS score at discharge was 3.2 (ranging from 1 to 5), showing some level of functional improvement. Conclusion: In conclusion, the use of the balloon-assisted tracking (BAT) technique for treating intracranial stenosis with distal thrombosis (IS&DT) showed promising results. However, a moderate rate of perioperative complications was observed, warranting further investigation and refinement of the procedure.

Comparison of survival benefit and safety between surgery following conversion therapy versus surgery alone in patients with surgically resectable hepatocellular carcinoma at CNLC IIb/IIIa stage: a propensity score matching study.

OBJECTIVE: The objective of this study is to evaluate and compare the survival benefit and safety of surgery following conversion therapy versus surgery alone in patients diagnosed with surgically resectable hepatocellular carcinoma (HCC) at China Liver Cancer Staging (CNLC) IIb/IIIa stage. METHODS: A total of 95 patients diagnosed with surgically resectable CNLC IIb/IIIa HCC were retrospectively enrolled in our study from November 2018 to December 2022. Among them, 30 patients underwent conversion therapy followed by hepatectomy, while the remaining 65 received surgery alone. The primary endpoint was recurrence-free survival (RFS). Propensity score matching was employed to minimize bias in the retrospective analysis. RESULTS: Compared to the surgery alone group, the conversion therapy group demonstrated a significantly prolonged median RFS (17.1 vs. 7.0 months; P =0.014), a reduced incidence of microvascular invasion (MVI, 23.3 vs. 81.5%; P <0.001), and a comparable rate of achieving Textbook Outcome in Liver Surgery (TOLS, 83.3 vs. 76.9%; P =0.476). Multivariate analysis indicated that conversion therapy was independently associated with improved RFS after hepatectomy (HR=0.511, P =0.027). The same conclusions were obtained after propensity score matching. CONCLUSIONS: The findings of our study offer preliminary evidence that preoperative conversion therapy significantly prolongs RFS in patients with surgically resectable HCC at CNLC IIb/IIIa stage. Furthermore, combining conversion therapy and hepatectomy represents a relatively safe treatment strategy.

Exploring the Rumen Microbiota and Serum Metabolite Profile of Hainan Black Goats with Different Body Weights before Weaning.

The critical role of the rumen microbiota in the growth performance of livestock is recognized, yet its significance in determining the body weight of goat kids before weaning remains less understood. To bridge this gap, our study delved into the rumen microbiota, serum metabolome, rumen fermentation, and rumen development in goat kids with contrasting body weights before weaning. We selected 10 goat kids from a cohort of 100, categorized into low body weight (LBW, 5.56 ± 0.98 kg) and high body weight (HBW, 9.51 ± 1.01 kg) groups. The study involved sampling rumen contents, tissues, and serum from these animals. Our findings showed that the HBW goat kids showed significant enrichment of VFA-producing bacteria, particularly microbiota taxa within the Prevotellaceae genera (UCG-001, UCG-003, and UCG-004) and the Prevotella genus. This enrichment correlated with elevated acetate and butyrate levels, positively influencing rumen papillae development. Additionally, it was associated with elevated serum levels of glucose, total cholesterol, and triglycerides. The serum metabonomic analysis revealed marked differences in fatty acid metabolism between the LBW and HBW groups, particularly in encompassing oleic acid and both long-chain saturated and polyunsaturated fatty acids. Further correlational analysis underscored a significant positive association between Prevotellaceae_UCG-001 and specific lipids, such as phosphatidylcholine (PC) (22:5/18:3) and PC (20:3/20:1) (r > 0.60, p < 0.05). In summary, this study underscores the pivotal role of the rumen microbiota in goat kids' weight and its correlation with specific serum metabolites. These insights could pave the way for innovative strategies aimed at improving animal body weight through targeted modulation of the rumen microbiota.

Rapid test to detect insecticide resistance in field populations of Spodoptera frugiperda (Lepidoptera: Noctuidae).

Introduction: The development of insecticide resistance in Spodoptera frugiperda populations is a serious threat to the crop industry. Given the spread of invasive resistant populations, prospective monitoring should be accelerated, and the development of diagnostic tools for rapid and accurate assessments of insecticide resistance is essential. Methods: First, the discriminating dose and diagnostic time of the kit were determined by the glass vial method based on a susceptible strain. Then, pests that were collected from field populations were used to determine their susceptibility to seven insecticides by using the diagnostic kit. Finally, the accuracy of the kit was verified based on correlation analyses and the likelihood of insecticide control failure was assessed. Results: Here, we describe a diagnostic kit that enables the rapid detection of resistance to chlorpyrifos, bifenthrin, deltamethrin, lambda-cyhalothrin, phoxim, chlorantraniliprole and chlorfenapyr within 1-2 h in S. frugiperda at diagnostic doses of 0.98, 0.84, 0.38, 1.64, 0.0082, 1.75 and 0.65 µg/cm2, respectively. The linear equation between mortalities under diagnostic doses and actual resistance ratios measured by the diet-overlay bioassay was determined. The high correlation indicates that the insecticide resistance levels diagnosed by the kit were consistent with the results of the diet-overlay bioassay. Moreover, we found a significant negative correlation between diagnostic mortality and the likelihood of control failure for bifenthrin (r = -0.899, p = 0.001), deltamethrin (r = -0.737, p = 0.024) and lambda-cyhalothrin (r = -0.871, p = 0.002). Discussion: The insecticide resistance diagnostic kit for S. frugiperda is a user-friendly tool (portable, short detection time). Its excellent performance qualifies the kit as a reliable screening tool for identifying effective insecticides in sustainable resistance management.

Role of exosomal noncoding RNA in esophageal carcinoma.

Esophageal cancer is a common malignant tumor with a high degree of malignancy. Understanding its pathogenesis and identifying early diagnostic biomarkers can significantly improve the prognosis of esophageal cancer patients. Exosomes are small double-membrane vesicles found in various body fluids containing various components (DNA, RNA, and proteins) that mediate intercellular signal communication. Non-coding RNAs are a class of gene transcription products that encode polypeptide functions and are widely detected in exosomes. There is growing evidence that exosomal non-coding RNAs are involved in cancer growth, metastasis and angiogenesis, and can also be used as diagnostic and prognostic markers. This article reviews the recent progress in exosomal non-coding RNAs in esophageal cancer, including research progress, diagnostic value, proliferation, migration, invasion, and drug resistance, provide new ideas for the precise treatment of esophageal cancer.

CRISPR-Cas12a Coupled with DNA Nanosheet-Amplified Fluorescence Anisotropy for Sensitive Detection of Biomolecules.

DNA nanosheets (DNSs) have been utilized effectively as a fluorescence anisotropy (FA) amplifier for biosensing. But, their sensitivity needs to be further improved. Herein, CRISPR-Cas12a with strong trans-cleavage activity was utilized to enhance the FA amplification ability of DNSs for the sensitive detection of miRNA-155 (miR-155) as a proof-of-principle target. In this method, the hybrid of the recognition probe of miR-155 (T1) and a blocker sequence (T2) was immobilized on the surface of magnetic beads (MBs). In the presence of miR-155, T2 was released by a strand displacement reaction, which activated the trans-cleavage activity of CRISPR-Cas12a. The single-stranded DNA (ssDNA) probe modified with a carboxytetramethylrhodamine (TAMRA) fluorophore was cleaved in large quantities and could not bind to the handle chain on DNSs, inducing a low FA value. In contrast, in the absence of miR-155, T2 could not be released and the trans-cleavage activity of CRISPR-Cas12a could not be activated. The TAMRA-modified ssDNA probe remained intact and was complementary to the handle chain on the DNSs, and a high FA value was obtained. Thus, miR-155 was detected through the obviously decreased FA value with a low limit of detection (LOD) of 40 pM. Impressively, the sensitivity of this method was greatly improved about 322 times by CRISPR-Cas12a, confirming the amazing signal amplification ability of CRISPR-Cas12a. At the same time, the SARS-CoV-2 nucleocapsid protein was detected by the strategy successfully, indicating that this method was general. Moreover, this method has been applied in the analysis of miR-155 in human serum and the lysates of cells, which provides a new avenue for the sensitive determination of biomarkers in biochemical research and disease diagnosis.

Development and validation of web-based prognostic nomograms for massive hepatocellular carcinoma (≥10 cm): A retrospective study based on the SEER database.

BACKGROUND AND AIMS: Massive hepatocellular carcinoma (MHCC, a maximum tumor size of at least 10 cm) tends to have a poor prognosis. Therefore, this study aims to construct and validate prognostic nomograms for MHCC. METHODS: Clinic data of 1292 MHCC patients between 2010 and 2015 were got from the surveillance, epidemiology, and end results (SEER) cancer registration database. The whole set was separated into the training and validation sets at a ratio of 2:1 randomly. Variables, significantly associated with cancer-specific (CSS) and overall survival (OS) of MHCC were figured out by multivariate Cox regression analysis and were taken to develop nomograms. The concordance index (C-index), calibration curve, and decision curve analysis (DCA) were taken to validate the predictive abilities and accuracy of the nomograms. RESULTS: Race, alpha-fetoprotein (AFP), grade, combined summary stage, and surgery were identified as independent factors of CSS, and fibrosis score, AFP, grade, combined summary stage, and surgery significantly correlated with OS in the training cohort. They then were taken to construct prognostic nomograms. The constructed model for predicting CSS exhibited satisfactory performance with a C-index of 0.727 (95% CI: 0.746-0.708) in the training group and 0. 672 (95% CI: 0.703-0.641) in the validation group. Besides, the model for predicting OS of MHCC also showed strong performance both in the training group (C-index: 0.722, 95% CI: 0.741-0.704) and the validation (C-index: 0.667, 95% CI: 0.696-0.638) group. All calibration curves and decision curves performed satisfactory predictive accuracy and clinic application values of the nomograms. CONCLUSION: The web-based nomograms for CSS and OS of MHCC were developed and validated in this study, which prospectively could be tested and may serve as additional tools to assess patient's individualized prognosis and make precise therapeutic selection to improve the poor outcome of MHCC.

CORDIC-Based General Multiple Fading Generator for Wireless Channel Digital Twin.

A wireless channel digital twin is a useful tool to evaluate the performance of a communication system at the physical or link level by generating the physical channel controllably. In this paper, a stochastic general fading channel model is proposed, which considered most of the channel fading types for various communication scenarios. By using the sum-of-frequency-modulation (SoFM) method, the phase discontinuity of the generated channel fading was well addressed. On this basis, a general and flexible generation architecture for channel fading was developed on a field programmable gate array (FPGA) platform. In this architecture, improved CORDIC-based hardware circuits for the trigonometric function, exponential function, and natural logarithm were designed and implemented, which improved the real-time performance of the system and the utilization rate of the hardware resources compared with the traditional LUT and CORDIC method. For a 16-bit fixed-point data bit width single-channel emulation, the hardware resource consumption was significantly reduced from 36.56% to 15.62% for the overall system by utilizing the compact time-division (TD) structure. Moreover, the classical CORDIC method brought an extra latency of 16 system clock cycles, while the latency caused by the improved CORDIC method was decreased by 62.5%. Finally, a generation scheme of a correlated Gaussian sequence was developed to introduce a controllable arbitrary space-time correlation for the channel generator with multiple channels. The output results of the developed generator were consistent with the theoretical results, which verified the correctness of both the generation method and hardware implementation. The proposed channel fading generator can be applied for the emulation of large-scale multiple-input, multiple-output (MIMO) channels under various dynamic communication scenarios.

Exploring the optical properties and molecular characteristics of dissolved organic matter in a large river-connected lake (Poyang Lake, China) using optical spectroscopy and FT-ICR MS analysis.

River-connected lakes are complicated and dynamic ecosystems due to their distinctive hydrological pattern, which could significantly impact the generation, degradation, and transformation processes of dissolved organic matter (DOM) and further regulate DOM chemistry in lakes. However, the molecular compositions and characteristics of DOM in river-connected lakes are still poorly understood. Thus, here the spatial variations of optical properties and molecular characteristics of DOM in a large river-connected lake (Poyang Lake) were explored via spectroscopic techniques and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). The results showed high degree of spatial heterogeneity of DOM chemistry (variations in DOC concentrations, optical parameters, and molecular compounds) in Poyang Lake, and the diversity at the molecular level was primarily caused by the heteroatom compounds (N- and S- containing). Compared with classic lakes and rivers, DOM compositions of the river-connected lake had distinctive characteristics (differences in the AImod and DBE values, and CHOS proportions). And the composition characteristics of DOM between the southern and northern parts of Poyang Lake were different (such as the lability and molecular compounds), suggesting the changes of hydrologic conditions may affect the DOM chemistry. In addition, various sources of DOM (autochthonous, allochthonous, and anthropogenic inputs) were identified agreeably based on optical properties and molecular compounds. Overall, this study first characterizes the DOM chemistry and reveals its spatial variations in Poyang Lake at the molecular level, which could improve our understanding of DOM in large river-connected lake systems. Further studies are encouraged to investigate the seasonal variations of DOM chemistry under different hydrologic conditions in Poyang Lake to enrich the knowledge of carbon cycling in river-connected lake systems.

Dietary Walnuts Preserve Aspects of Health Span and Alter the Hippocampal Lipidome in Aged High-Fat Diet-Fed Mice.

Evidence continues to accrue that aging and its diseases can be delayed by pharmacologic and dietary strategies that target the underlying hallmarks of the aging process. However, identifying simple, safe, and effective dietary strategies involving the incorporation of whole foods that may confer some protection against the aging process is also needed. Recent observational studies have suggested that nut consumption can reduce mortality risk in humans. Among these, walnuts are particularly intriguing, given their high content of n-3 fatty acids, fiber, and antioxidant and anti-inflammatory compounds. To this end, 12-month-old male CB6F1 mice were provided either a defined control low-fat diet (LFD), a control high-fat diet (HFD), or an isocaloric HFD containing 7.67% walnuts by weight (HFD + W), and measures of healthspan and related biochemical markers (n = 10-19 per group) as well as survival (n = 20 per group) were monitored. Mice provided the HFD or HFD + W demonstrated marked weight gain, but walnuts lowered baseline glucose (p < 0.05) and tended to temper the effects of HFD on liver weight gain (p < 0.05) and insulin tolerance (p = 0.1). Additional assays suggested a beneficial effect on some indicators of health with walnut supplementation, including preservation of exercise capacity and improved short-term working memory, as determined by Y maze (p = 0.02). However, no effect was observed via any diet on inflammatory markers, antioxidant capacity, or survival (p = 0.2). Ingenuity Pathway Analysis of the hippocampal transcriptome identified two processes predicted to be affected by walnuts and potentially linked to cognitive function, including estrogen signaling and lipid metabolism, with changes in the latter confirmed by lipidomic analysis. In summary, while walnuts did not significantly improve survival on a HFD, they tended to preserve features of healthspan in the context of a metabolic stressor with aging.

Role of Zerumbone, a Phytochemical Sesquiterpenoid from Zingiber zerumbet Smith, in Maintaining Macrophage Polarization and Redox Homeostasis.

Macrophages and microglia are highly versatile cells that can be polarized into M1 and M2 phenotypes in response to diverse environmental stimuli, thus exhibiting different biological functions. In the central nervous system, activated resident macrophages and microglial cells trigger the production of proinflammatory mediators that contribute to neurodegenerative diseases and psychiatric disorders. Therefore, modulating the activation of macrophages and microglia by optimizing the inflammatory environment is beneficial for disease management. Several naturally occurring compounds have been reported to have anti-inflammatory and neuroprotective properties. Zerumbone is a phytochemical sesquiterpenoid and also a cyclic ketone isolated from Zingiber zerumbet Smith. In this study, we found that zerumbone effectively reduced the expression of lipocalin-2 in macrophages and microglial cell lines. Lipocalin-2, also known as neutrophil gelatinase-associated lipocalin (NGAL), has been characterized as an adipokine/cytokine implicated in inflammation. Moreover, supplement with zerumbone inhibited reactive oxygen species production. Phagocytic activity was decreased following the zerumbone supplement. In addition, the zerumbone supplement remarkably reduced the production of M1-polarization-associated chemokines CXC10 and CCL-2, as well as M1-polarization-associated cytokines interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α. Furthermore, the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 and the production of NO were attenuated in macrophages and microglial cells supplemented with zerumbone. Notably, we discovered that zerumbone effectively promoted the production of the endogenous antioxidants heme oxygenase-1, glutamate-cysteine ligase modifier subunit, glutamate-cysteine ligase catalytic subunit, and NAD(P)H quinone oxidoreductase-1 and remarkably enhanced IL-10, a marker of M2 macrophage polarization. Endogenous antioxidant production and M2 macrophage polarization were increased through activation of the AMPK/Akt and Akt/GSK3 signaling pathways. In summary, this study demonstrated the protective role of zerumbone in maintaining M1 and M2 polarization homeostasis by decreasing inflammatory responses and enhancing the production of endogenous antioxidants in both macrophages and microglia cells. This study suggests that zerumbone can be used as a potential therapeutic drug for the supplement of neuroinflammatory diseases.

The Caenorhabditis elegans ARIP-4 DNA helicase couples mitochondrial surveillance to immune, detoxification, and antiviral pathways.

Surveillance of Caenorhabditis elegans mitochondrial status is coupled to defense responses such as drug detoxification, immunity, antiviral RNA interference (RNAi), and regulation of life span. A cytochrome p540 detoxification gene, cyp-14A4, is specifically activated by mitochondrial dysfunction. The nuclear hormone receptor NHR-45 and the transcriptional Mediator component MDT-15/MED15 are required for the transcriptional activation of cyp-14A4 by mitochondrial mutations, gene inactivations, or toxins. A genetic screen for mutations that fail to activate this cytochrome p450 gene upon drug or mutation-induced mitochondrial dysfunction identified a DNA helicase ARIP-4 that functions in concert with the NHR-45 transcriptional regulatory cascade. In response to mitochondrial dysfunction, ARIP-4 and NHR-45 protein interaction is enhanced, and they relocalize from the nuclear periphery to the interior of intestinal nuclei. NHR-45/ARIP-4 also regulates the transcriptional activation of the eol-1 gene that encodes a decapping enzyme required for enhanced RNAi and transgene silencing of mitochondrial mutants. In the absence of arip-4, animals were more susceptible to the mitochondrial inhibitor antimycin. Thus, ARIP-4 serves as a transcriptional coactivator of NHR-45 to promote this defense response. A null mutation in arip-4 extends the life span and health span of both wild type and a mitochondrial mutant, suggesting that the activation of detoxification pathways is deleterious to health when the mitochondrial dysfunction is caused by mutation that cannot be cytochrome p450-detoxified. Thus, arip-4 acts in a pathway that couples mitochondrial surveillance to the activation of downstream immunity, detoxification, and RNAi responses.

Circular RNA circSFMBT2 downregulation by HBx promotes hepatocellular carcinoma metastasis via the miR-665/TIMP3 axis.

Hepatitis B virus X protein (HBx) is considered as an oncogene in tumorigenesis and progression of hepatocellular carcinoma (HCC). In recent years, the important role of circular RNAs (circRNAs) in HCC has been increasingly demonstrated. However, the regulatory mechanisms of HBx on circRNAs remains largely unknown. In this study, we identified that a novel circRNA, circSFMBT2, was markedly downregulated by HBx. Low expression of circSFMBT2 was correlated with poor prognosis and vascular invasion. Functionally, overexpression of circSFMBT2 significantly inhibited HCC metastasis both in vitro and in vivo. The mechanism of circSFMBT2 was to as a sponge of miR-665, which is a negative regulator of tissue inhibitor of metalloproteinases 3 (TIMP3). However, HBx downregulated circSFMBT2 via the interaction with DExH-box helicase 9 (DHX9), which binds to flanking circRNA-forming introns. In conclusion, circSFMBT2, which is downregulated by HBx, acts as a tumor suppressor to inhibit tumor metastasis through the miR-665/TIMP3 axis. Our study suggests that circSFMBT2 could be a potential prognostic biomarker and therapeutic target for HCC.