Prognosis and diagnosis of prostate cancer based on hypergraph regularization sparse least partial squares regression algorithm.

BACKGROUND: Prostate cancer (PCa) is a malignant tumor of the male reproductive system, and its incidence has increased significantly in recent years. This study aimed to further identify candidate biomarkers with prognostic and diagnostic significance by integrating gene expression and DNA methylation data from PCa patients through association analysis. MATERIAL AND METHODS: To this end, this paper proposes a sparse partial least squares regression algorithm based on hypergraph regularization (HR-SPLS) by integrating and clustering two kinds of data. Next, module 2, with the most significant weight, was selected for further analysis according to the weight of each module related to DNA methylation and mRNAs. Based on the DNA methylation sites in module 2, this paper uses multiple machine learning methods to construct a PCa diagnosis-related model of 10-DNA methylation sites. RESULTS: The results of Receiver Operating Characteristic (ROC) analysis showed that the DNA methylation-related diagnostic model we constructed could diagnose PCa patients with high accuracy. Subsequently, based on the mRNAs in module 2, we constructed a prognostic model for 7-mRNAs (MYH11, ACTG2, DDR2, CDC42EP3, MARCKSL1, LMOD1, and MYLK) using multivariate Cox regression analysis. The prognostic model could predict the disease free survival of PCa patients with moderate to high accuracy (area under the curve (AUC) =0.761). In addition, Gene Set EnrichmentAnalysis (GSEA) and immune analysis indicated that the prognosis of patients in the risk group might be related to immune cell infiltration. CONCLUSIONS: Our findings may provide new methods and insights for identifying disease-related biomarkers by integrating DNA methylation and gene expression data.

Community Assembly Processes of Deadwood Mycobiome in a Tropical Forest Revealed by Long-Read Third-Generation Sequencing.

Despite the importance of wood-inhabiting fungi on nutrient cycling and ecosystem functions, their ecology, especially related to their community assembly, is still highly unexplored. In this study, we analyzed the wood-inhabiting fungal richness, community composition, and phylogenetics using PacBio sequencing. Opposite to what has been expected that deterministic processes especially environmental filtering through wood-physicochemical properties controls the community assembly of wood-inhabiting fungal communities, here we showed that both deterministic and stochastic processes can highly contribute to the community assembly processes of wood-inhabiting fungi in this tropical forest. We demonstrated that the dynamics of stochastic and deterministic processes varied with wood decomposition stages. The initial stage was mainly governed by a deterministic process (homogenous selection), whereas the early and later decomposition stages were governed by the stochastic processes (ecological drift). Deterministic processes were highly contributed by wood physicochemical properties (especially macronutrients and hemicellulose) rather than soil physicochemical factors. We elucidated that fine-scale fungal-fungal interactions, especially the network topology, modularity, and keystone taxa of wood-inhabiting fungal communities, strongly differed in an initial and decomposing deadwood. This current study contributes to a better understanding of the ecological processes of wood-inhabiting fungi in tropical regions where the knowledge of wood-inhabiting fungi is highly limited.

Salvia miltiorrhiza suppresses cardiomyocyte ferroptosis after myocardial infarction by activating Nrf2 signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Ferroptosis, a recently identified non-apoptotic form of cell death reliant on iron, is distinguished by an escalation in lipid reactive oxygen species (ROS) that are iron-dependent. This phenomenon has a strong correlation with irregularities in iron metabolism and lipid peroxidation. Salvia miltiorrhiza Bunge (DS), a medicinal herb frequently utilized in China, is highly esteemed for its therapeutic effectiveness in enhancing blood circulation and ameliorating blood stasis, particularly during the treatment of cardiovascular diseases (CVDs). Numerous pharmacological studies have identified that DS manifests antioxidative stress effects as well as inhibits lipid peroxidation. However, ambiguity persists regarding the potential of DS to impede ferroptosis in cardiomyocytes and subsequently improve myocardial damage post-myocardial infarction (MI). AIM OF THE STUDY: The present work focused on investigating whether DS could be used to prevent the ferroptosis of cardiomyocytes and improve post-MI myocardial damage. MATERIALS AND METHODS: In vivo experiments: Through ligation of the left anterior descending coronary artery, we constructed both a wild-type (WT) and NF-E2 p45-related factor 2 knockout (Nrf2-/-) mouse model of MI. Effects of DS and ferrostatin-1 (Fer-1) on post-MI cardiomyocyte ferroptosis were examined through detecting ferroptosis and myocardial damage-related indicators as well as Nrf2 signaling-associated protein levels. In vitro experiments: Erastin was used for stimulating H9C2 cardiomyocytes to construct an in vitro ferroptosis cardiomyocyte model. Effects of DS and Fer-1 on cardiomyocyte ferroptosis were determined based on ferroptosis-related indicators and Nrf2 signaling-associated protein levels. Additionally, inhibitor and activator of Nrf2 were used for confirming the impact of Nrf2 signaling on DS's effect on cardiomyocyte ferroptosis. RESULTS: In vivo: In comparison to the model group, DS suppressed ferroptosis in cardiomyocytes post-MI and ameliorated myocardial damage by inducing Nrf2 signaling-related proteins (Nrf2, xCT, GPX4), diminishing tissue ferrous iron and malondialdehyde (MDA) content. Additionally, it enhanced glutathione (GSH) levels and total superoxide dismutase (SOD) activity, effects that are aligned with those of Fer-1. Moreover, the effect of DS on alleviating cardiomyocyte ferroptosis after MI could be partly inhibited through Nrf2 knockdown. In vitro: Compared with the erastin group, DS inhibited cardiomyocyte ferroptosis by promoting the expression of Nrf2 signaling-related proteins, reducing ferrous iron, ROS, and MDA levels, but increasing GSH content and SOD activity, consistent with the effect of Fer-1. Additionally, Nrf2 inhibition increased erastin-mediated ferroptosis of cardiomyocytes through decreasing Nrf2 signaling-related protein expressions. Co-treatment with DS and Nrf2 activator failed to further enhance the anti-ferroptosis effect of DS. CONCLUSION: MI is accompanied by cardiomyocyte ferroptosis, whose underlying mechanism is probably associated with Nrf2 signaling inhibition. DS possibly suppresses ferroptosis of cardiomyocytes and improves myocardial damage after MI through activating Nrf2 signaling.

Rapid Discovery of Substances with Anticancer Potential from Marine Fungi Based on a One Strain-Many Compounds Strategy and UPLC-QTOF-MS.

The secondary metabolites of marine fungi with rich chemical diversity and biological activity are an important and exciting target for natural product research. This study aimed to investigate the fungal community in Quanzhou Bay, Fujian, and identified 28 strains of marine fungi. A total of 28 strains of marine fungi were screened for small-scale fermentation by the OSMAC (One Strain-Many Compounds) strategy, and 77 EtOAc crude extracts were obtained and assayed for cancer cell inhibition rate. A total of six strains of marine fungi (P-WZ-2, P-WZ-3-2, P-WZ-4, P-WZ-5, P56, and P341) with significant changes in cancer cell inhibition induced by the OSMAC strategy were analysed by UPLC-QTOF-MS. The ACD/MS Structure ID Suite software was used to predict the possible structures with inhibitory effects on cancer cells. A total of 23 compounds were identified, of which 10 compounds have been reported to have potential anticancer activity or cytotoxicity. In this study, the OSMAC strategy was combined with an untargeted metabolomics approach based on UPLC-QTOF-MS to efficiently analyse the effect of changes in culture conditions on anticancer potentials and to rapidly find active substances that inhibit cancer cell growth.

Identification of new variants in MTRNR1 and MTRNR2 genes using whole mitochondrial genome sequencing in a Taiwanese family with MERRF (myoclonic epilepsy with ragged-red fibers) syndrome.

Mitochondrial encephalomyopathy is a multi-system disorder mostly caused by inborn errors of the oxidative phosphorylation (OXPHOS) system and usually manifested as complex neurological disorder and muscle weakness. Myoclonic epilepsy with ragged-red fibers (MERRF) syndrome is one of the major subtypes of mitochondrial disease associated with the m.8344A>G mutation in mitochondrial tRNALys gene. In addition to the symptoms in central nervous and muscle systems, a portion of the patients may develop hearing loss, which has been linked to the genetic mutations of mitochondrial DNA (mtDNA) especially in the mitochondrial ribosome RNA (rRNA) gene. Despite a great number of studies focusing on the consequences of mtDNA mutations, the mechanism of pathogenesis of these overt diseases has remained unclear, and there is no specific and effective treatment for MERRF syndromes. In this study, we developed a high-quality mtDNA sequencing method by next generation sequencing technology to search for the additional pathogenic variations of mtDNA from skin fibroblasts of four members in a Taiwanese family with MERRF syndrome. Through uncovering the signatures of all mtDNA variants in the MERRF family, we identified novel mtDNA variants in the genes encoding mitochondrial 12S and 16S rRNAs. The finding from this study will give us further insight into the molecular mechanisms driving the phenotypic variability and timing of onset of the MERRF syndrome.

Ferrostatin-1 suppresses cardiomyocyte ferroptosis after myocardial infarction by activating Nrf2 signaling.

OBJECTIVES: Ferroptosis, a new regulated cell death pathway, plays a crucial part in the development of cardiovascular disease. However, the precise underlying mechanism remains unclear. Therefore, this study aimed to elucidate this. METHODS: Herein, an erastin-induced H9C2 cell ferroptosis in vitro model and a myocardial infarction murine model, which was created by ligating the left anterior descending coronary artery, were established. Ferroptosis-related indicators, myocardial injury-related indicators, and Nrf2 signaling-related proteins expression were analyzed to explore the potential mechanism underlying cardiomyocyte ferroptosis-mediated cardiovascular disease development. RESULTS: We demonstrated that Nrf2 downregulation in myocardial tissue, accompanied by ferroptotic events and changes in xCT and GPX4 expressions, induced cardiomyocyte ferroptosis and myocardial injury after myocardial infarction. These events, including ferroptosis and changes in Nrf2, xCT, and GPX4 expressions, were improved by ferrostatin-1 in vivo and in vitro. Besides, Nrf2 deficiency or inhibition aggravated myocardial infarction-induced cardiomyocyte ferroptosis by decreasing xCT and GPX4 expressions in vivo and in vitro. Moreover, ferrostatin-1 directly targeted Nrf2, as evidenced by surface plasmon resonance analysis. CONCLUSIONS: These results indicated that myocardial infarction is accompanied by cardiomyocyte ferroptosis and that Nrf2 signaling plays a crucial part in regulating cardiomyocyte ferroptosis after myocardial infarction.

Role of MEG3 in Cellular Physiology of Atherosclerosis.

OBJECTIVE: To investigate the role of the lncRNA MEG3 (MEG3) in opposing the biochemical processes thought to be involved in the development of atherosclerosis (AS). METHODS: Thirty patients with AS and thirty healthy control subjects were enrolled in this study. The expression of MEG3, miR-200b-3p and ABCA1 was analyzed by RT-qPCR in the individuals and the macrophages-derived foam cells. Lipid accumulation was detected by oil red O staining. Cholesterol efflux was measured by ELISA assay in the foam cells. Expression of miR-200b-3p was identified by sequencing. Targeting relationships were determined by dual luciferase assay between MEG3 and miR-200b-3p, miR-200b-3p and ABCA1. RESULTS: In the patients with AS, MEG3 and ABCA1 expression were decreased and miR-200b-3p expression was upregulated. Foam cells transfected with an expression vector (pcDNA3.1) containing MEG3 (pcDNA3.1-MEG3) induced decrease of lipid accumulation and increase of cholesterol efflux compared to cells transfected with control plasmid alone. Foam cells transfected by pcDNA3.1-MEG3 also showed decreased miR-200b-3p and increased ABCA1 expression. Interestingly, co-expression of miR-200b-3p partially prevented these effects of MEG3 expression. CONCLUSION: Expression of MEG3 is downregulated in the patients with AS and foam cells. Overexpressed MEG3 may act as an anti-atherosclerotic factor by reducing lipid accumulation and accelerating cholesterol efflux through the miR-200b-3p/ABCA1 axis.

Morph-specific fitness throughout the life cycle of the grain aphid, nonhost-alternating, holocyclic Sitobion avenae (Hemiptera: Aphididae).

Aphids exhibit seasonally alternating asexual and sexual reproductive modes. Different morphs are produced throughout the life cycle. To evaluate morph-specific fitness during reproductive switching, holocyclic Sitobion avenae were induced continuously under short light conditions, and development and reproduction were compared in each morph. Seven morphs, including apterous and alate virginoparae, apterous and alate sexuparae, oviparae, males, and fundatrices, were produced during the life cycle. The greatest proportions of sexuparae, oviparae, males, and virginoparae were in the G1, G2, G3, and G4 generations, respectively. Regardless of asexual or sexual morphs, alate morphs exhibited a marked delay in age at maturity compared with that of apterous morphs. Among the alate morphs, males had the longest age at maturity, followed by sexuparae and virginoparae. Among the apterous morphs, sexuparae were older at maturity than the fundatrices, virginoparae, and oviparae. The nymphs of each morph had equal survival potentials. For the same wing morphs, apterous sexuparae and oviparae exhibited substantial delays in the pre-reproductive period and considerable reductions in fecundity, compared with those of apterous virginoparae and fundatrices, whereas alate sexuparae and alate virginoparae had similar fecundity. The seven morphs exhibited Deevey I survivorship throughout the life cycle. These results suggest that sexual production, particularly in males, has short-term development and reproduction costs. The coexistence of sexual and asexual morphs in sexuparae offspring may be regarded as an adaptive strategy for limiting the risk of low fitness in winter.

Mitochondrial impairment and synaptic dysfunction are associated with neurological defects in iPSCs-derived cortical neurons of MERRF patients.

BACKGROUND: Myoclonic epilepsy with ragged-red fibers (MERRF) syndrome is a rare inherited mitochondrial disease mainly caused by the m.8344A > G mutation in mitochondrial tRNALys gene, and usually manifested as complex neurological disorders and muscle weakness. Currently, the pathogenic mechanism of this disease has not yet been resolved, and there is no effective therapy for MERRF syndrome. In this study, MERRF patients-derived iPSCs were used to model patient-specific neurons for investigation of the pathogenic mechanism of neurological disorders in mitochondrial disease. METHODS: MERRF patient-derived iPSCs were differentiated into excitatory glutamatergic neurons to unravel the effects of the m.8344A > G mutation on mitochondrial bioenergetic function, neural-lineage differentiation and neuronal function. By the well-established differentiation protocol and electrophysiological activity assay platform, we examined the pathophysiological behaviors in cortical neurons of MERRF patients. RESULTS: We have successfully established the iPSCs-derived neural progenitor cells and cortical-like neurons of patients with MERRF syndrome that retained the heteroplasmy of the m.8344A > G mutation from the patients' skin fibroblasts and exhibited the phenotype of the mitochondrial disease. MERRF neural cells harboring the m.8344A > G mutation exhibited impaired mitochondrial bioenergetic function, elevated ROS levels and imbalanced expression of antioxidant enzymes. Our findings indicate that neural immaturity and synaptic protein loss led to the impairment of neuronal activity and plasticity in MERRF neurons harboring the m.8344A > G mutation. By electrophysiological recordings, we monitored the in vivo neuronal behaviors of MERRF neurons and found that neurons harboring a high level of the m.8344A > G mutation exhibited impairment of the spontaneous and evoked potential-stimulated neuronal activities. CONCLUSIONS: We demonstrated for the first time the link of mitochondrial impairment and synaptic dysfunction to neurological defects through impeding synaptic plasticity in excitatory neurons derived from iPSCs of MERRF patients harboring the m.8344A > G mutation. This study has provided new insight into the pathogenic mechanism of the tRNALys gene mutation of mtDNA, which is useful for the development of a patient-specific iPSCs platform for disease modeling and screening of new drugs to treat patients with MERRF syndrome.

Effect of regio-specific arylamine substitution on novel π-extended zinc salophen complexes: density functional and time-dependent density functional study on DSSC applications.

A series of π-extended salophen-type Schiff-base zinc(ii) complexes, e.g., zinc-salophen complexes (ZSC), were investigated toward potential applications for dye-sensitized solar cells. The ZSC dyes adopt linear-, X-, or π-shaped geometries either with the functionalization of 1 donor/1 acceptor or 2 donors/2 acceptors to achieve a push-pull type molecular structure. The frontier molecular orbitals, light-harvesting properties as well as charge transfer characters against regio-specific substitution of donor/acceptor groups were studied by using density functional theory (DFT) and time-dependent density functional theory (TDDFT). The results reveal that all ZSC dyes of D-ZnS-π-A geometry (where D, S, and A denote to donor, salophen ligand, and acceptor, respectively) exhibit relatively lower HOMO energy compared to the structurally resembled porphyrin dye YD2-o-C8. Natural transition orbital (NTO) and electron-hole separation (EHS) approaches clearly differentiate the linear type YD-series dyes from CL-, AJ1-, and AJ2-series dyes because of poor charge transfer (CT) properties. In contrast, the π-shaped AJ2-series and X-shaped AJ1-series dyes outperform the others in a manner of stronger CT characteristics, broadened UV-vis absorption as well as tunable bandgap simply via substitution of p-ethynylbenzoic acids (EBAs) and arylamine donors at salophen 7,8- and 2,3,12,13-positions, respectively. Both EHS and calculated exciton binding energies suggest the strength of CT character for ZSC dyes with an amino donor in the trend TPA > AN > DPA. This work has provided clear illustration toward molecular design of efficient dyes featuring a zinc-salophen backbone.

Empirical research on the friction behavior of O-rings in hydraulic cylinders.

Mechanical products are becoming more diversified with the continuous development of precision processing and materials technologies. The friction force generated by the O-ring seal in a hydraulic cylinder was once considered redundant. However, its utilization has recently been proposed. The hardness of the O-ring and the inner diameter of its groove directly affect the normal pressure between the O-ring and the inner wall of the cylinder, thereby affecting the friction behavior. In order to explore this friction behavior, a strain-based friction force measurement system is developed in this study, and the steady-state and dynamic friction values under different working conditions are studied and discussed in depth. This research on the friction behavior in the cylinder provides a theoretical basis for more convenient design and utilization of the friction force generated between the O-ring and the inner wall of the cylinder.

The ecdysis triggering hormone system is essential for reproductive success in Mythimna separata (Walker).

Ecdysis triggering hormone (ETH) was originally discovered as a key hormone that regulates insect moulting via binding to its receptor, ETH receptor (ETHR). However, the precise role of ETH in moth reproduction remains to be explored in detail. ETH function was verified in vivo using Mythimna separata (Walker), an important cereal crop pest. RT-qPCR analysis revealed that transcriptional expression profiles of MsepETH showed evident sexual dimorphism in the adult stage. MsepETH expression increased in the females on day 3 and persisted thereafter till day 7, consistent with female ovarian maturation, and was merely detectable in males. Meanwhile, MsepETH expression levels were significantly higher in the trachea than in other tissues. MsepETHR-A and MsepETHR-B were expressed in both sexes and were significantly higher in the antennae than in other tissues. MsepETH and MsepETHR knockdown in females by RNA interference significantly reduced the expression of MsepETH, MsepETHR-A, MsepETHR-B, MsepJHAMT, and MsepVG, which delayed egg-laying and significantly reduced egg production. RNAi 20-hydroxyecdysone (20E) receptor (EcR) decreased MsepETH expression whereas injecting 20E restored egg production that had been disrupted by MsepETH interference. Meanwhile, RNAi juvenile hormone (JH) methoprene tolerant protein (Met) also decreased MsepETH expression and smearing JH analog methoprene (Meth) restored egg production. In conclusion, the reproduction roles of ETH, JH, and 20E were investigated in M. separata. These findings will lay the foundation for future research to develop an antagonist that reduces female reproduction and control strategies for pest insects.

Future climate conditions accelerate wheat straw decomposition alongside altered microbial community composition, assembly patterns, and interaction networks.

Although microbial decomposition of plant litter plays a crucial role in nutrient cycling and soil fertility, we know less about likely links of specific microbial traits and decomposition, especially in relation to climate change. We study here wheat straw decomposition under ambient and manipulated conditions simulating a future climate scenario (next 80 years) in agroecosystems, including decay rates, macronutrient dynamics, enzyme activity, and microbial communities. We show that future climate will accelerate straw decay rates only during the early phase of the decomposition process. Additionally, the projected climate change will increase the relative abundance of saprotrophic fungi in decomposing wheat straw. Moreover, the impact of future climate on microbial community assembly and molecular ecological networks of both bacteria and fungi will strongly depend on the decomposition phase. During the early phase of straw decomposition, stochastic processes dominated microbial assembly under ambient climate conditions, whereas deterministic processes highly dominated bacterial and fungal communities under simulated future climate conditions. In the later decomposition phase, similar assembly processes shaped the microbial communities under both climate scenarios. Furthermore, over the early phases of decomposition, simulated future climate enhanced the complexity of microbial interaction networks. We concluded that the impact of future climate on straw decay rate and associated microbial traits like assembly processes and inter-community interactions is restricted to the early phase of decomposition.

Environmental Variables Including Heavy Metals Significantly Shape the Soil Bacterial Community Structure in the Tatun Volcano Group, Northern Taiwan.

Recent studies suggested the presence of magma chambers from the Tatun volcano group under northern Taiwan's surface, the result of episodic volcanism for 0.2-2.8 million years. However, the microbial community in volcanic soil has not yet been characterized. Therefore, the present study investigated the spatial distribution of microbial communities and their relationships with environmental variables, including heavy metals. Next-generation sequencing was used to analyze the microbial community structures in three areas with different land uses: Lengshuikeng (recreational area), Zhuzihu (agricultural area), and Huangzuishan (conservation area). High contents of environmental factors, such as nitrogen (0.46-1.14%) and phosphorus (2.01-13.88 ppm), were detected. Large concentrations of heavy metals, such as copper (55.90-127.60 ppm) and zinc (36.13-147.73 ppm), were found among the three sites, whereas those of lead (83.13 ppm) and chromium (48.33 ppm) were higher in the Zhuzihu area. The most prevalent phylum across all sites was Proteobacteria, followed by Actinobacteria, Acidobacteria, and Chloroflexi, while the most abundant bacterial species was Koribacteraceae: NA_01, followed by Cyanobacteria: NA. A network ana-lysis showed that Koribacteracea: NA_01 positively correlated with bacterial groups, including Flavisolibacter sp., Oxalobacteraceae: NA, and Actinomycetales: NA_01. Based on Shannon and Simpson's diversity indices, the diversity of bacteria was significantly less in the Huangzuishan area than in the Lengshuikeng and Zhuzihu areas. Bacterial assemblages also significantly differed (P<0.05) among the three sites. The present results provide clear evidence to show that environmental variables, including heavy metals, are key factors affecting the bacterial community structure in volcanic soil.

Classification of contrast-enhanced ultrasonograms in rectal cancer according to tumor inhomogeneity using machine learning-based texture analysis.

Background: Inhomogeneity within tumors can reflect tumor angiogenesis. Existing research into the quantization of angiogenesis mainly focuses on time-intensity curve parameters but has produced inconsistent results. In clinical work, it is difficult to achieve standardization and consistency for manual judgement of the inhomogeneity of contrast-enhanced images, while the artificial intelligence technology may be helpful. The aim of this study was to assess whether computers can assist in the artificial classification of tumor inhomogeneity in contrast-enhanced ultrasound (CEUS) images of rectal cancer. Methods: A total of 500 contrast-enhanced ultrasonograms were retrospectively collected, which was verified of rectal cancer pathologically from 2016 to 2018 as training set. All images are from 18-80 years old patients with rectal cancer in our hospital. These tumors are usually located in the middle and lower segment of the rectum, which can be completely observed on ultrasound. The images were divided into 3 categories according to the inhomogeneous distribution of contrast agents inside the tumors. Computing methods were used to simulate manual classification. Computer processing steps included segmentation, gray level quantization, dimension reduction, and classification. The results of 6 different gray level quantization, 2 dimensionality reduction methods, and 3 classifiers were compared, from which the optimal parameters were selected in each step. The performance of computer classification was evaluated using manual classification results as the reference. Ninety-seven ultrasonograms of contrast-enhanced rectal tumors were collected as validation set from 2018.1 to 2018.6. Results: The optimal gray level was set at 32. Principal component analysis (PCA) was the first choice for dimensionality reduction. The best classifier was support vector machines (SVM). The accuracy of computer classification was 87.80% (439/500). The accuracy of computer classification in the validation cohort was 60.82%. The area under the curve (AUC) of class 1, 2, and 3 were 0.76, 0.41, and 0.48, respectively. Conclusions: Results showed that the computer methods are competent for classifying inhomogeneity of contrast-enhanced rectal cancers inside ultrasonograms.

Corrigendum to "Ginsenoside Ro, an oleanolic saponin of Panax ginseng, exerts anti-inflammatory effect by direct inhibiting toll like receptor 4 signaling pathway" [J Ginseng Res 46 (2022) 156-166].

[This corrects the article DOI: 10.1016/j.jgr.2021.05.011.].

Effects of Tolerance-Induced Preconditioning on Mitochondrial Biogenesis in Undifferentiated and Differentiated Neuronal Cells.

BACKGROUND: Mitochondrial biogenesis occurs in response to chronic stresses as an adaptation to the increased energy demands and often renders cells more refractive to subsequent injuries which is referred to as preconditioning. This phenomenon is observed in several non-neuronal cell types, but it is not yet fully established in neurons, although it is fundamentally important for neuroprotection and could be exploited for therapeutic purposes. METHODS: This study was designed to examine whether the preconditioning treatment with hypoxia or nitric oxide could trigger biogenesis in undifferentiated and differentiated neuronal cells (rat PC12 and human NT2 cells) as well as in primary mouse cortical neurons. RESULTS: The results showed that both preconditioning paradigms induced mitochondrial biogenesis in undifferentiated cell lines, as indicated by an increase of mitochondrial mass (measured by flow cytometry of NAO fluorescence) and increased expression of genes required for mitochondrial biogenesis (Nrf1, Nrf2, Tfam, Nfκb1) and function (Cox3, Hk1). All these changes translated into an increase in the organelle copy number from an average of 20-40 to 40-60 mitochondria per cell. The preconditioning treatments also rendered the cells significantly less sensitive to the subsequent oxidative stress challenge brought about by oxygen/glucose deprivation, consistent with their improved cellular energy status. Mitochondrial biogenesis was abolished when preconditioning treatments were performed in the presence of antioxidants (vitamin E or CoQ10), indicating clearly that ROS-signaling pathway(s) played a critical role in the induction of this phenomenon in undifferentiated cells. However, mitochondrial biogenesis could not be re-initiated by preconditioning treatments in any of the post-mitotic neuronal cells tested, i.e., neither rat PC12 cells differentiated with NGF, human NT2 cells differentiated with retinoic acid nor mouse primary cortical neurons. Instead, differentiated neurons had a much higher organelle copy number per cell than their undifferentiated counterparts (100-130 mitochondria per neuron vs. 20-40 in proliferating cells), and this feature was not altered by preconditioning. CONCLUSIONS: Our study demonstrates that mitochondrial biogenesis occurred during the differentiation process resulting in more beneficial energy status and improved tolerance to oxidative stress in neurons, putting in doubt whether additional enhancement of this phenomenon could be achieved and successfully exploited as a way for better neuroprotection.

Impacts of offshore wind farms on the atmospheric environment over Taiwan Strait during an extreme weather typhoon event.

Wind is one of the cleanest renewable energy resources. Through the "Thousand Wind Turbines Project", Taiwan is planning to increase the proportion of power generation from renewable energy and has set a target of 5.7 GW for offshore wind by 2025. The effects of future offshore wind farms (OWFs) over the Taiwan Strait on the atmospheric environment have not been evaluated. This study examined the potential effects of proposed OWFs on the atmospheric environment if the OWFs had existed during Tropical Storm Haitang (2017) by using Weather Research and Forecasting (WRF) model. A small set of ensemble simulations was conducted for studying the sensitivity of the ambient conditions in the region to the wind farm locations, the number and density of the turbines, and the initial time of simulations. Following the landfall and northward movement of Tropical Storm Haitang, a series of complex interactions between the typhoon circulation and the wind farm emerged, including small time slots of wake effect and mountain blocking effect. The combination of these rapidly changing OWFs-related effects contributed to a weak reduction in precipitation (- 1.08 mm) and hub-height wind speed (- 0.25 m s-1), as well as minimal warming near the surface (+ 0.13 °C) over southern Taiwan.

The value of multi-modes of ultrasound in evaluating segmental mucosal healing in patients with Crohn's disease.

BACKGROUND: Mucosal healing, the result of endoscopic remission, is associated with prolonged clinical remission and delayed deterioration of Crohn's disease, which is significant and accompanied by reduced hospitalizations and surgeries. Currently, the relationship between ultrasonic parameters and mucosal healing remains controversial. To establish an ultrasonic regression model to evaluate mucosal healing, we conducted this preliminary study using multiple parameters from B-mode ultrasonography, colour Doppler flow imaging and shear wave elastography systematically. METHODS: This study consisted of two single-centre investigations based on development and validation populations who received endoscopies (as the gold standard) and ultrasound. The involved bowel segments were divided into mucosal healing (MH) and nonmucosal healing (NMH) groups according to endoscopic results. Eight ultrasonic parameters were observed, including bowel wall thickness (BWT), mesenteric fat thickness (MFT), median modulus of elasticity (Emean), average shear wave velocity (SWV), Limberg scoring (LG), bowel wall stratification (BWS), ascites (AS) and lymph node enlargement (LN). We developed an ultrasonic regression model in the development phase to evaluate segmental mucosal healing and undertook prospective validation of this model. RESULTS: A total of 124 patients with 380 involved bowel segments from the development and validation cohorts were evaluated. Eight ultrasonic parameters were significantly different between the two groups (P<0.05) in the development phase. Four significant parameters with better AUC performance were selected to establish an ultrasonic regression model to predict mucosal healing. The AUCs of this ultrasonic model were 0.975 and 0.942 in the development and validation cohorts, respectively. CONCLUSION: The multimodal ultrasonic model has the potential to evaluate segmental mucosal healing in Crohn's disease.

Ginsenoside Ro, an oleanolic saponin of Panax ginseng, exerts anti-inflammatory effect by direct inhibiting toll like receptor 4 signaling pathway.

BACKGROUND: Panax ginseng Meyer (P. ginseng), a herb distributed in Korea, China and Japan, exerts benefits on diverse inflammatory conditions. However, the underlying mechanism and active ingredients remains largely unclear. Herein, we aimed to explore the active ingredients of P. ginseng against inflammation and elucidate underlying mechanisms. METHODS: Inflammation model was constructed by lipopolysaccharide (LPS) in C57BL/6 mice and RAW264.7 macrophages. Molecular docking, molecular dynamics, surface plasmon resonance imaging (SPRi) and immunofluorescence were utilized to predict active component. RESULTS: P. ginseng significantly inhibited LPS-induced lung injury and the expression of pro-inflammatory factors, including TNF-α, IL-6 and IL-1ß. Additionally, P. ginseng blocked fluorescence-labeled LPS (LPS488) binding to the membranes of RAW264.7 macrophages, the phosphorylation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs). Furthermore, molecular docking demonstrated that ginsenoside Ro (GRo) docked into the LPS binding site of toll like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD2) complex. Molecular dynamic simulations showed that the MD2-GRo binding conformation was stable. SPRi demonstrated an excellent interaction between TLR4/MD2 complex and GRo (KD value of 1.16 × 10-9 M). GRo significantly inhibited LPS488 binding to cell membranes. Further studies showed that GRo markedly suppressed LPS-triggered lung injury, the transcription and secretion levels of TNF-α, IL-6 and IL-1ß. Moreover, the phosphorylation of NF-κB and MAPKs as well as the p65 subunit nuclear translocation were inhibited by GRo dose-dependently. CONCLUSION: Our results suggest that GRo exerts anti-inflammation actions by direct inhibition of TLR4 signaling pathway.