[Effect of Erchen Decoction on liver mitochondrial function by inhibiting mTORC1/SREBP1/CAV1 pathway in mice with high-fat diet].

This study aims to investigate the effect of Erchen Decoction(ECD) on liver mitochondrial function in mice with a high-fat diet and its possible mechanism. A total of sixty C57BL/6J mice were randomly divided into a normal group, high-fat group, ECD group, mTORC1 activator(MHY) group, ECD+MHY group, and polyene phosphatidyl choline(PPC) group, with 10 rats in each group. The normal group was given a normal diet, and the other groups were fed a high-fat diet for 20 weeks. At the 17th week, the ECD group and ECD+MHY group were given ECD(8.7 g·kg~(-1)) daily, and the PPC group was given PPC(0.18 g·kg~(-1)) daily, while the remaining groups were given normal saline(0.01 mL·g~(-1)) daily for four weeks. In the 19th week, the MHY group and ECD+MHY group were injected intraperitoneally with MHY(5 mg·kg~(-1)) every other day for two weeks. During the experiment, the general conditions of the mice were observed. The contents of triglyceride(TG) and total cholesterol(TC) in serum were measured. Morphological changes in liver tissue were examined through HE and oil red O staining. The content of adenosine triphosphate(ATP) was determined using chemiluminescence, and mitochondrial membrane potential was assessed using a fluorescence probe(JC-1). Western blot was performed to detect the expression of rapamycin target protein complex 1(mTOR1), ribosomal protein S6 kinase B1(S6K), sterol regulatory element binding protein 1(SREBP1), and caveolin 1(CAV1). RESULTS:: revealed that compared with the normal group, the mice in the high-fat group exhibited significant increases in body weight and abdominal circumference(P<0.01). Additionally, there were significant increases in TG and TC levels(P<0.01). HE and oil red O staining showed that the boundaries of hepatic lobules were unclear; hepatocytes were enlarged, round, and irregularly arranged, with obvious lipid droplet deposition and inflammatory cell infiltration. The liver ATP content and mitochondrial membrane potential decreased significantly(P<0.01). The expression of p-mTOR, p-S6K, and n-SREBP1 increased significantly(P<0.01), while the expression of CAV1 decreased significantly(P<0.01). Compared with the high-fat group, the body weight and TG content of mice in the ECD group and PPC group decreased significantly(P<0.05). Improvements were observed in hepatocyte morphology, lipid deposition, and inflammatory cell infiltration. Furthermore, there were significant increases in ATP content and mitochondrial membrane potential(P<0.05 or P<0.01). The expression of p-mTOR, p-S6K, and n-SREBP1 decreased significantly in the ECD group(P<0.01), while CAV1 expression increased significantly(P<0.01). However, the indices mentioned above did not show improvement in the MHY group. When the ECD+MHY group was compared with the MHY group, there were significant reductions in body weight and TG contents(P<0.05). The morphological changes of hepatocytes, lipid deposition, and inflammatory cell infiltration were recovered. Moreover, there were significant increases in liver ATP content and mitochondrial membrane potential(P<0.05 or P<0.05). The expression of p-mTOR, p-S6K, and n-SREBP1 decreased significantly(P<0.01), while CAV1 expression increased significantly(P<0.01). In conclusion, ECD can improve mitochondrial function by regulating the mTORC1/SREBP1/CAV1 pathway. This mechanism may be involved in the resolution of phlegm syndrome and the regulation of lipid metabolism.

EPOR activation attenuates colitis via enhancing LC3B-dependent apoptotic cell clearance.

Systemic immune activation and excessive inflammatory response, induced by intestinal barrier damage, are the major characteristics of inflammatory bowel disease (IBD). Excessive apoptotic cell accumulation leads to the production of a large number of inflammatory factors, further aggravating IBD development. Gene set enrichment analysis data showed that the homodimeric erythropoietin receptor (EPOR) was highly expressed in the whole blood of patients with IBD. EPOR is specifically expressed in intestinal macrophages. However, the role of EPOR in IBD development is unclear. In this study, we found that EPOR activation significantly alleviated colitis in mice. Furthermore, in vitro, EPOR activation in bone marrow-derived macrophage (BMDMs) promoted microtubule-associated protein 1 light chain 3B (LC3B) activation and mediated the clearance of apoptotic cells. Moreover, our data showed that EPOR activation facilitated the expression of phagocytosis- and tissue-repair-related factors. Our findings suggest that EPOR activation in macrophages promotes apoptotic cell clearance, probably via LC3B-associated phagocytosis (LAP), providing a new mechanism for understanding pathological progression and a novel potential therapeutic target for colitis.

Biogeographic diversification of Actaea (Ranunculaceae): Insights into the historical assembly of deciduous broad-leaved forests in the Northern Hemisphere.

The deciduous broad-leaved forests (DBLFs) cover large temperate and subtropical high-altitude regions in the Northern Hemisphere. They are home to rich biodiversity, especially to numerous endemic and relict species. However, we know little about how this vegetation in the Northern Hemisphere has developed through time. Here, we used Actaea (Ranunculaceae), an herbaceous genus almost exclusively growing in the understory of the Northern Hemisphere DBLFs, to shed light on the historical assembly of this biome in the Northern Hemisphere. We present a complete species-level phylogenetic analysis of Actaea based on five plastid and nuclear loci. Using the phylogenetic framework, we estimated divergence times, ancestral ranges, and diversification rates. Phylogenetic analyses strongly support Actaea as monophyletic. Sections Podocarpae and Oligocarpae compose a clade, sister to all other Actaea. The sister relationship between sections Chloranthae and Souliea is strongly supported. Section Dichanthera is not monophyletic unless section Cimicifuga is included. Actaea originated in East Asia, likely the Qinghai-Tibet Plateau, in the late Paleocene (c. 57 Ma), and subsequently dispersed into North America in the middle Eocene (c. 43 Ma) via the Thulean bridge. Actaea reached Europe twice, Japan twice, and Taiwan once, and all these five colonization events occurred in the late Miocene-early Pliocene, a period when sea level dropped. Actaea began to diversify at c. 43 Ma. The section-level diversification took place at c. 27-37 Ma and the species-level diversification experienced accelerations twice, which occurred at c. 15 Ma and c. 5 Ma, respectively. Our findings suggest that the Northern Hemisphere DBLFs might have risen in the middle Eocene and further diversified in the late Eocene-Oligocene, middle Miocene and early Pliocene, in association with climatic deterioration during these four periods.

Development and validation of an RNA sequencing panel for gene fusions in soft tissue sarcoma.

Gene fusions are one of the most common genomic alterations in soft tissue sarcomas (STS), which contain more than 70 subtypes. In this study, a custom-designed RNA sequencing panel including 67 genes was developed and validated to identify gene fusions in STS. In total, 92 STS samples were analyzed using the RNA panel and 95.7% (88/92) successfully passed all the quality control parameters. Fusion transcripts were detected in 60.2% (53/88) of samples, including three novel fusions (MEG3-PLAG1, SH3BP1-NTRK1, and RPSAP52-HMGA2). The panel demonstrated excellent analytic accuracy, with 93.9% sensitivity and 100% specificity. The intra-assay, inter-assay, and personnel consistencies were all 100.0% in four samples and three replicates. In addition, different variants of ESWR1-FLI, COL1A1-PDGFB, NAB2-STAT6, and SS18-SSX were also identified in the corresponding subtypes of STS. In combination with histological and molecular diagnosis, 14.8% (13/88) patients finally changed preliminary histology-based classification. Collectively, this RNA panel developed in our study shows excellent performance on RNA from formalin-fixed, paraffin-embedded samples and can complement DNA-based assay, thereby facilitating precise diagnosis and novel fusion detection.

CsiLAC4 modulates boron flow in Arabidopsis and Citrus via high-boron-dependent lignification of cell walls.

The mechanisms underlying plant tolerance to boron (B) excess are far from fully understood. Here we characterized the role of the miR397-CsiLAC4/CsiLAC17 (from Citrus sinensis) module in regulation of B flow. Live-cell imaging techniques were used in localization studies. A tobacco transient expression system tested modulations of CsiLAC4 and CsiLAC17 by miR397. Transgenic Arabidopsis were generated to analyze the biological functions of CsiLAC4 and CsiLAC17. CsiLAC4's role in xylem lignification was determined by mRNA hybridization and cytochemistry. In situ B distribution was analyzed by laser ablation inductively coupled plasma mass spectrometry. CsiLAC4 and CsiLAC17 are predominantly localized in the apoplast of tobacco epidermal cells. Overexpression of CsiLAC4 in Arabidopsis improves the plants' tolerance to boric acid excess by triggering high-B-dependent lignification of the vascular system's cell wall and reducing free B content in roots and shoots. In Citrus, CsiLAC4 is expressed explicitly in the xylem parenchyma and is modulated by B-responsive miR397. Upregulation of CsiLAC4 in Citrus results in lignification of the xylem cell walls, restricting B flow from xylem vessels to the phloem. CsiLAC4 contributes to plant tolerance to boric acid excess via high-B-dependent lignification of cell walls, which set up a 'physical barrier' preventing B flow.

Blind Watermarking for Hiding Color Images in Color Images with Super-Resolution Enhancement.

This paper presents a novel approach for directly hiding the pixel values of a small color watermark in a carrier color image. Watermark embedding is achieved by modulating the gap of paired coefficient magnitudes in the discrete cosine transform domain according to the intended pixel value, and watermark extraction is the process of regaining and regulating the gap distance back to the intensity value. In a comparison study of robustness against commonly encountered attacks, the proposed scheme outperformed seven watermarking schemes in terms of zero-normalized cross-correlation (ZNCC). To render a better visual rendition of the recovered color watermark, a generative adversarial network (GAN) was introduced to perform image denoising and super-resolution reconstruction. Except for JPEG compression attacks, the proposed scheme generally resulted in ZNCCs higher than 0.65. The employed GAN contributed to a noticeable improvement in perceptual quality, which is also manifested as high-level ZNCCs of no less than 0.78.

Utility of Whole Genome Sequencing in Assessing and Enhancing Partner Notification of Neisseria gonorrhoeae Infection.

BACKGROUND: Gonorrhea is a sexually transmitted infection of global concern. We investigated whole-genome sequencing (WGS) as a tool to measure and enhance partner notification (PN) in gonorrhea management. METHODS: Between May and November 2018, all N. gonorrhoeae isolated from patients attending Leeds Sexual Health, United Kingdom, underwent WGS. Reports listing sequences within 20 single-nucleotide polymorphisms (SNPs) of study isolates within a database containing select isolates from April 1, 2016, to November 15, 2018, were issued to clinicians. The proportion of cases with a potential transmission partner identified by PN was determined from patient and PN data. The WGS reports were reviewed to identify additional cases within 6 SNPs or less and verified for PN concordance. RESULTS: Three hundred eighty isolates from 377 cases were successfully sequenced; 292 had traceable/contactable partners and 69 (18%) had a potential transmission partner identified by PN. Concordant PN and WGS links were identified in 47 partner pairs. Of 308 cases with no transmission partner by PN, 185 (60%) had a case within 6 SNPs or less; examination of these cases' PN data identified 7 partner pairs with previously unrecognized PN link, giving a total of 54 pairs; all had 4 or less SNP differences. The WGS clusters confirmed gaps in partner finding, at individual and group levels. Despite the clinic providing sexual health services to the whole city, 35 cases with multiple partners had no genetically related case, suggesting multiple undiagnosed infections. CONCLUSIONS: Whole-genome sequencing could improve gonorrhea PN and control by identifying new links and clusters with significant gaps in partner finding.

Metabolomics Study of Flavonoids of Taxilluschinensis on Different Hosts Using UPLC-ESI-MS/MS.

The goal of this study was to identify and compare the main biomarkers of Taxillus chinensis from different hosts. A metabolomics approach utilizing ultra-pressure liquid chromatography coupled with tandem mass spectrometry (UPLC-MS), including cluster analysis, sample correlation analysis and orthogonal partial least squares discriminant analysis, was used to explore the flavonoid metabolites of Taxillus chinensis growing on different hosts. Results: The total flavonoids content (up to 30.08 mg/g) in Taxillus chinensis from Morus alba (CSG) was significantly higher than that from growth on Liquidambar formosana (CFG) or Clausena lansium (CHG) (p < 0.01). There were 23 different metabolites between CSG and CHG, 23 different metabolites between CSG and CFG, and 19 different metabolites between CHG and CFG. The results demonstrated that different hosts exerted a large influence on the metabolites of Taxillus chinensis; it was found that CSG differed from CFG and CHG in eleven metabolic compounds, ten of which were upregulated and one of which was downregulated. Most of these metabolites derive from compounds contained in the host plant, white mulberry (Morus alba); many feature potent anti-cancer effects. Differences in host can influence the type and abundance of flavonoids in parasitic plants such as Taxillus chinensis, which is of great significance to researchers seeking to understand the formation mechanism of Taxillus chinensis metabolites. Therefore, attention should be paid to the species of host plant when studying the Taxillus chinensis metabolome. Plants grown on Morus alba offer the greatest potential for the development of new anti-cancer drugs.

Foodborne transmission of Clostridioides difficile: a review.

PURPOSE OF REVIEW: The epidemiology of Clostridioides difficile infection (CDI) is changing, with increasing rates of community-acquired infections. In light of recent advances in understanding C. difficile transmission networks with whole-genome sequencing, new routes of spread outside the hospital need to be considered. This review examines the evidence behind food as a driver of C. difficile dissemination. RECENT FINDINGS: Recently published studies adding to the existing body of literature supporting C. difficile as a foodborne pathogen are discussed. Specifically, new evidence on the presence of C. difficile in root vegetables is reviewed. Whole genome sequencing studies delineating local and global transmission networks, in which the food chain may play a large role, are presented. Additional research implicating trehalose in the food industry and C. difficile is examined. SUMMARY: Genomic studies show that a new approach to studying C. difficile transmission is needed. Further research on C. difficile epidemiology should shift from a primarily nosocomial setting to include the community and environment at large, and attention given to implications of the food chain in the spread of this pathogen.

Understanding Clostridium difficile Colonization.

Clostridium difficile is the main causative agent of antibiotic-associated and health care-associated infective diarrhea. Recently, there has been growing interest in alternative sources of C. difficile other than patients with Clostridium difficile infection (CDI) and the hospital environment. Notably, the role of C. difficile-colonized patients as a possible source of transmission has received attention. In this review, we present a comprehensive overview of the current understanding of C. difficile colonization. Findings from gut microbiota studies yield more insights into determinants that are important for acquiring or resisting colonization and progression to CDI. In discussions on the prevalence of C. difficile colonization among populations and its associated risk factors, colonized patients at hospital admission merit more attention, as findings from the literature have pointed to their role in both health care-associated transmission of C. difficile and a higher risk of progression to CDI once admitted. C. difficile colonization among patients at admission may have clinical implications, although further research is needed to identify if interventions are beneficial for preventing transmission or overcoming progression to CDI.

Clostridium difficile: Investigating Transmission Patterns Between Infected and Colonized Patients Using Whole Genome Sequencing.

Background: Whole genome sequencing (WGS) studies can enhance our understanding of the role of patients with asymptomatic Clostridium difficile colonization in transmission. Methods: Isolates obtained from patients with Clostridium difficile infection (CDI) and colonization identified in a study conducted during 2006-2007 at 6 Canadian hospitals underwent typing by pulsed-field gel electrophoresis, multilocus sequence typing, and WGS. Isolates from incident CDI cases not in the initial study were also sequenced where possible. Ward movement and typing data were combined to identify plausible donors for each CDI case, as defined by shared time and space within predefined limits. Proportions of plausible donors for CDI cases that were colonized, infected, or both were examined. Results: Five hundred fifty-four isolates were sequenced successfully, 353 from colonized patients and 201 from CDI cases. The NAP1/027/ST1 strain was the most common strain, found in 124 (62%) of infected and 92 (26%) of colonized patients. A donor with a plausible ward link was found for 81 CDI cases (40%) using WGS with a threshold of ≤2 single nucleotide polymorphisms to determine relatedness. Sixty-five (32%) CDI cases could be linked to both infected and colonized donors. Exclusive linkages to infected and colonized donors were found for 28 (14%) and 12 (6%) CDI cases, respectively. Conclusions: Colonized patients contribute to transmission, but CDI cases are more likely linked to other infected patients than colonized patients in this cohort with high rates of the NAP1/027/ST1 strain, highlighting the importance of local prevalence of virulent strains in determining transmission dynamics.

The perils of PCR-based diagnosis of Clostridioides difficile infections: Painful lessons from clinical trials.

Diagnostic tests favoured to detect C. difficile infections (CDI) have undergone successive changes. The problem of over-diagnosis with polymerase chain reaction (PCR) testing is recognized in the clinical setting; here we discuss the parallel of the clinical trial setting. We summarize and discuss four examples of the impact of method used to diagnose CDI on clinical trial outcomes. Bezlotoxumab, a human monoclonal antibody neutralizing toxin B, was found to be protective against recurrent CDI (rCDI) in clinical trials. A post hoc analysis showed that the magnitude of the relative reduction in rCDI rates of bezlotoxumab over placebo in patients diagnosed with toxin-based testing was almost double that in patients diagnosed with PCR. SER-109, a microbiome therapeutic developed to prevent rCDI, showed promise in a phase 1b trial, but results were not replicated in a phase 2 trial in which diagnosis was in majority PCR-based. Surotomycin, an oral lipopeptide antibiotic, was found to be non-inferior to vancomycin in phase 2 study, but development was discontinued after unfavourable phase 3 results in which the majority of CDI were diagnosed by PCR. Finally, a C. difficile vaccine program for a toxoid vaccine developed by Sanofi/Pasteur was terminated after interim analysis of a phase 3 trial, in which CDI diagnosis was based solely on PCR. We highlighted the perils of using PCR alone in studies involving different aspects of C. difficile clinical research, including immunotherapies, microbiome-based therapies, treatments, and vaccines. The importance of designing C. difficile clinical trials with careful consideration to the diagnostic testing method cannot be overemphasized.

MicroRNA Sequencing Revealed Citrus Adaptation to Long-Term Boron Toxicity through Modulation of Root Development by miR319 and miR171.

Boron (B) toxicity in Citrus is a common physiological disorder leading to reductions in both productivity and quality. Studies on how Citrus roots evade B toxicity may provide new insight into plant tolerance to B toxicity. Here, using Illumina sequencing, differentially expressed microRNAs (miRNAs) were identified in B toxicity-treated Citrus sinensis (tolerant) and C. grandis (intolerant) roots. The results showed that 37 miRNAs in C. grandis and 11 miRNAs in C. sinensis were differentially expressed when exposed to B toxicity. Among them, miR319, miR171, and miR396g-5p were confirmed via 5'-RACE and qRT-PCR to target a myeloblastosis (MYB) transcription factor gene, a SCARECROW-like protein gene, and a cation transporting ATPase gene, respectively. Maintenance of SCARECROW expression in B treated Citrus roots might fulfill stem cell maintenance, quiescent center, and endodermis specification, thus allowing regular root elongation under B-toxic stress. Down-regulation of MYB due to up-regulation of miR319 in B toxicity-treated C. grandis roots might decrease the number of root tips, thereby dramatically changing root system architecture. Our findings suggested that miR319 and miR171 play a pivotal role in Citrus adaptation to long-term B toxicity by targeting MYB and SCARECROW, respectively, both of which are responsible for root growth and development.

Circular RNA: new star, new hope in cancer.

BACKGROUND: Circular RNAs are a new class of endogenous non-coding RNA that can function as crucial regulators of diverse cellular processes. The diverse types of circular RNAs with varying cytogenetics in cancer have also been reported. Circular RNAs can act as a microRNA sponge or through other mechanisms to regulate gene expression as either tumor inhibitors or accelerators, suggesting that circular RNAs can serve as newly developed biomarkers with clinic implications. Here, we summerized recent advances on circular RNAs in cancer and described a circular RNA network associated with tumorigenesis. The clinical implications of circular RNAs in cancer were also discussed in this paper. SHORT CONCLUSION: Growing evidence has revealed the crucial regulatory roles of circular RNAs in cancer and the elucidation of functional mechanisms involving circular RNAs would be helpful to construct a circRNA-miRNA-mRNA regulatory network. Moreover, circular RNAs can be easily detected due to their relative stability, widespread expression, and abundance in exosomes, blood and saliva; thus, circular RNAs have potential as new and ideal clinical biomarkers in cancer.

Electron donor and acceptor functionalized dithienylethenes: effects of charge density on photochromic properties.

Electron-donating triphenylamine and/or electron-withdrawing pyromellitic diimide (PMDI) are functionalized on dithienylethene (DTE) and three novel photochromic materials have been designed and successfully synthesized. All the compounds display reversible photochromism due to the molecular switching between ring-closed isomers upon UV light irradiation and ring-open isomers upon exposure to visible light. Thus they can be applied as an anti-counterfeiting ink. Moreover, the study of the photoswitching kinetics reveals that both the ring-closing and ring-opening reactions are first-order reactions. Further charge population analysis discovers that the electron densities of the substituents at the DTE core have a dramatic influence on the photochromic properties. The incorporation of electron-donating triphenylamine groups at the α-position of the thiophene rings in the DTE unit facilitates the ring-closing reaction upon UV light irradiation. In contrast, the substitution of an electron-withdrawing PMDI unit in the DTE unit is beneficial to the ring-opening reaction upon irradiation of visible light. This work may help to understand the photochromism of DTE derivatives and provide a pathway for designing DTE-based photochromes with more or less sensitivity to UV or visible light.

Travel-Related Infections Among Pregnant Travellers to the Tropics: An Overview.

Infectious diseases acquired during travel pose a significant health risk to pregnant travellers, who are more susceptible to both acquiring certain infections and developing severe complications. A review of the literature focusing on recent evidence-based guidelines was conducted with attention to tropical infections in the pregnant patient. A summary meant to serve as a succinct reference for health care professionals caring for pregnant women is presented. Magnitude of risk, clinical features, management, and preventive strategies of major travel-acquired infections of pertinence to the pregnant traveller are summarized, including malaria, arboviral infections, foodborne infections, helminthic infections, and influenza. Tables with details on specific infections within each group and guidance for reducing travel-related health risks in the pregnant patient are presented.

Association of serum C1q/TNF-related protein-3 (CTRP-3) in patients with coronary artery disease.

BACKGROUND: Recent studies have demonstrated that complement C1q tumor necrosis factor related proteins (CTRPs) have diverse biological influences on the cardiovascular system. CTRP 3 is a member of the CTRP superfamily, which may play a pivotal role in the pathogenesis of coronary artery disease (CAD). Here, we investigated whether serum levels of CTRP 3 are associated with the prevalence and the severity of CAD. METHODS: In this study, 145 eligible participants were included who underwent coronary angiography. According to the result of the coronary angiography, all participants were divided into two groups: non-CAD group (n = 66) and CAD group (n = 79). The CAD group was further divided into single-vessel (n = 25), double-vessel (n = 30) and triple-vessel (n = 24) disease groups in line with different lesioned vessels of CAD. Plasma CTRP 3 concentration was determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum levels of CTRP 3 were significantly higher in CAD patients than in non-CAD patients (CAD: 56.68 ± 3.63 ng/ml, non-CAD: 44.10 ± 3.20 ng/ml, p < 0.01). Significant differences of CTRP 3 levels were also found between single-vessel group and triple-vessel group (single-vessel group: 44.80 ± 3.14 ng/ml, triple-vessel group: 75.07 ± 9.41 ng/ml, p < 0.005). Multiple logistic regression analysis revealed that CTRP 3 levels, together with HDL cholesterol and glucose, correlated with CAD. CONCLUSIONS: Elevated serum CTRP 3 levels were closely related to the prevalence and severity of CAD, suggesting that it might be regarded as a novel biomarker for CAD.

Theoretical imaging study of early caries by a laser induced Rayleigh wave.

Vivo human teeth are scanned by computed tomography through three-dimensional (3D) reconstruction technology. Geometric models of teeth are built. Based on that, a physical model of the laser induced acoustic waves propagating in teeth is established, and the finite element method is used to solve this physical model. As the velocity of the Rayleigh wave is sensitive to the elastic modulus of the teeth, the parameters, such as the position, demineralization degree, depth, and morphology of the caries, can be evaluated by the velocity field of the Rayleigh wave, which propagate in teeth. Furthermore, by the frequency domain characters of surface acoustic waves, the depth of the caries region can be evaluated. Therefore, the 3D evaluation method is established to develop the nondestructive and quantitative detection of the early stages of caries.