Enabling Quasi-Zero-Strain Behavior of Layered Oxide Cathodes via Multiple-cations Induced Order-to-Disorder Transition.

The chemically pre-intercalated lattice engineering is widely applied to elevate the electronic conductivity, expand the interlayer spacing, and improve the structural stability of layered oxide cathodes. However, the mainstream unitary metal ion pre-intercalation generally produces the cation/vacancy ordered superstructure, which astricts the further improvement of lattice respiration and charge-carrier ion storage and diffusion. Herein, a multiple metal ions pre-intercalation lattice engineering is proposed to break the cation/vacancy ordered superstructure. Taking the bilayer V2O5 as an example, Ni, Co, and Zn ternary ions are simultaneously pre-intercalated into its interlayer space (NiCoZnVO). It is revealed that the Ni─Co neighboring characteristic caused by Ni(3d)-O(2p)-Co(3d) orbital coupling and the Co-Zn/Ni-Zn repulsion effect due to chemical bond incompatibility, endow the NiCoZnVO sample with the cation/vacancy disordered structure. This not only reduces the Li+ diffusion barrier, but also increases the diffusion dimension of Li+ (from one-dimension to two-dimension). Particularly, Ni, Co, and Zn ions co-pre-intercalation causes a prestress, which realizes a quasi-zero-strain structure at high-voltage window upon charging/discharging process. The functions of Ni ion stabilizing the lattice structure and Co or Zn ions activating more Li+ reversible storage reaction of V5+/V4+ are further revealed. The cation/vacancy disordered structure significantly enhances Li+ storage properties of NiCoZnVO cathode.

Metabolite-based genome-wide association studies enable the dissection of the genetic bases of flavonoids, betaine and spermidine in wolfberry (Lycium).

Wolfberry is a plant with medicinal and food values. However, its bioactive ingredients and the corresponding genetic bases have not been determined. Here, we de novo generated a chromosome-level genome assembly for wolfberry, yielding a genome sequence of ~1.77 Gb with contig N50 of 50.55 Mb and 39 224 predicted gene models. A variation map, using 307 re-sequenced accessions, was called based on this genome assembly. Furthermore, the fruit metabolome of these accessions was profiled using 563 annotated metabolites, which separated Lycium barbarum L. and non-L. barbarum L. The flavonoids, coumarins, alkaloids and nicotinic acid contents were higher in the former than in the latter. A metabolite-based genome-wide association study mapped 156 164 significant single nucleotide polymorphisms corresponding to 340 metabolites. This included 19 219 unique lead single nucleotide polymorphisms in 1517 significant association loci, of which three metabolites, flavonoids, betaine and spermidine, were highlighted. Two candidate genes, LbUGT (evm.TU.chr07.2692) and LbCHS (evm.TU.chr07.2738), with non-synonymous mutations, were associated with the flavonoids content. LbCHS is a structural gene that interacts with a nearby MYB transcription factor (evm.TU.chr07.2726) both in L. barbarum and L. ruthenicum. Thus, these three genes might be involved in the biosynthesis/metabolism of flavonoids. LbSSADH (evm.TU.chr09.627) was identified as possibly participating in betaine biosynthesis/metabolism. Four lycibarbarspermidines (E-G and O) were identified, and only the lycibarbarspermidines O content was higher in L. barbarum varieties than in non-L. barbarum varieties. The evm.TU.chr07.2680 gene associated with lycibarbarspermidines O was annotated as an acetyl-CoA-benzylalcohol acetyltransferase, suggesting that it is a candidate gene for spermidine biosynthesis. These results provide novel insights into the specific metabolite profile of non-L. barbarum L. and the genetic bases of flavonoids, betaine and spermidine biosynthesis/metabolism.

α-Mangostin reduces hypertension in spontaneously hypertensive rats and inhibits EMT and fibrosis in Ang II-induced HK-2 cells.

Hypertension affects a large number of individuals globally and is a common cause of nephropathy, stroke, ischaemic heart disease and other vascular diseases. While many anti-hypertensive medications are used safely and effectively in clinic practice, controlling hypertensive complications solely by reducing blood pressure (BP) can be challenging. α-Mangostin, a xanthone molecule extracted from the pericarp of Garcinia mangostana L., has shown various beneficial effects such as anti-tumor, anti-hyperuricemia, and anti-inflammatory properties. However, the effects of α-Mangostin on hypertension remain unknown. In this study, we observed that α-Mangostin significantly decreased systolic and diastolic blood pressure in spontaneously hypertensive rats (SHR), possibly through the down-regulation of angiotensin II (Ang II). We also identified early markers of hypertensive nephropathy, including urinary N-acetyl-ß-D-glucosaminidase (NAG) and ß2-microglobulin (ß2-MG), which were reduced by α-Mangostin treatment. Mechanistic studies suggested that α-Mangostin may inhibit renal tubular epithelial-to-mesenchymal transformation (EMT) by down-regulating the TGF-ß signaling pathway, thus potentially offering a new therapeutic approach for hypertension and hypertensive nephropathy.

Bulk segregation analysis in the NGS era: a review of its teenage years.

Bulk segregation analysis (BSA) utilizes a strategy of pooling individuals with extreme phenotypes to conduct economical and rapidly linked marker screening or quantitative trait locus (QTL) mapping. With the development of next-generation sequencing (NGS) technology in the past 10 years, BSA methods and technical systems have been gradually developed and improved. At the same time, the ever-decreasing costs of sequencing accelerate NGS-based BSA application in different species, including eukaryotic yeast, grain crops, economic crops, horticultural crops, trees, aquatic animals, and insects. This paper provides a landscape of BSA methods and reviews the BSA development process in the past decade, including the sequencing method for BSA, different populations, different mapping algorithms, associated region threshold determination, and factors affecting BSA mapping. Finally, we summarize related strategies in QTL fine mapping combining BSA.

Exploration of eMSCs with HA-GEL system in repairing damaged endometrium after endometrial cancer with fertility-sparing treatment.

Despite the high complete response rate of fertility-sparing treatment in early-stage endometrial cancer (EC), the low pregnancy rate is a clinical challenge. Whether endometrium-derived mesenchymal stem cells (eMSCs) can repair damaged endometrium after EC reversal remains unclear. This study explored the potential therapeutic effects of eMSCs with suitable scaffold materials on endometrial damage caused by EC. Here, appropriate engineering scaffold materials were compared to identify the most suitable materials to carry eMSCs. Then, safety and efficacy evaluations of eMSCs with a suitable hyaluronic acid hydrogel (eMSCs/HA-GEL) were investigated in in vivo experiments with subcutaneous xenotransplantation in Balb/C nude mice and a model of endometrial mechanical injury in rats. HA-GEL has minimal cytotoxicity to eMSCs compared to other materials. Then, in vitro experiments demonstrate that eMSCs/HA-GEL enhance the inhibitory effects of progestins on EC cell biological behaviors. eMSCs/HA-GEL significantly inhibit EC cell growth and have no potential safety hazards of spontaneous tumorigenesis in Balb/C nude mouse subcutaneous xenotransplantation assays. eMSCs/HA-GEL intrauterine transplantation effectively increases endometrial thickness and glandular number, improves endometrial blood supply, reduces fibrotic areas, and improves pregnancy rates in a rat endometrial mechanical injury model. GFP-eMSCs/HA-GEL intrauterine transplantation in rats shows more GFP-eMSCs in the endometrium than GFP-eMSCs transplantation alone, and no tumor formation or suspicious cell nodules are found in the liver, kidney, or lung tissues. Our results reveal the safety and efficacy of eMSCs/HA-GEL in animal models and provide preliminary evidence for the use of eMSCs/HA-GEL as a treatment for EC-related endometrial damage.

Patients' Experiences of a National Patient Portal and Its Usability: Cross-Sectional Survey Study.

BACKGROUND: Patient portals not only provide patients with access to electronic health records (EHRs) and other digital health services, such as prescription renewals, but they can also improve patients' self-management, engagement with health care professionals (HCPs), and care processes. However, these benefits depend on patients' willingness to use patient portals and, ultimately, their experiences with the usefulness and ease of use of the portals. OBJECTIVE: This study aimed to investigate the perceived usability of a national patient portal and the relationship of patients' very positive and very negative experiences with perceived usability. The study was aimed to be the first step in developing an approach for benchmarking the usability of patient portals in different countries. METHODS: Data were collected through a web-based survey of the My Kanta patient portal's logged-in patient users in Finland from January 24, 2022, to February 14, 2022. Respondents were asked to rate the usability of the patient portal, and the ratings were used to calculate approximations of the System Usability Scale (SUS) score. Open-ended questions asked the patients about their positive and negative experiences with the patient portal. The statistical analysis included multivariate regression, and the experience narratives were analyzed using inductive content analysis. RESULTS: Of the 1,262,708 logged-in patient users, 4719 responded to the survey, giving a response rate of 0.37%. The patient portal's usability was rated as good, with a mean SUS score of 74.3 (SD 14.0). Reporting a very positive experience with the portal was positively associated with perceived usability (ß=.51; P<.001), whereas reporting a very negative experience was negatively associated with perceived usability (ß=-1.28; P<.001). These variables explained 23% of the variation in perceived usability. The information provided and a lack of information were the most common positive and negative experiences. Furthermore, specific functionalities, such as prescription renewal and the ease of using the patient portal, were often mentioned as very positive experiences. The patients also mentioned negative emotions, such as anger and frustration, as part of their very negative experiences. CONCLUSIONS: The study offers empirical evidence about the significant role of individual experiences when patients are evaluating the usability of patient portals. The results suggest that positive and negative experiences provide relevant information that can be used for improving the patient portal's usability. Usability should be improved so that patients receive information efficiently, easily, and quickly. Respondents would also appreciate interactive features in the patient portal.

Molecular mapping for fruit-related traits, and joint identification of candidate genes and selective sweeps for seed size in melon.

Melon is a popular fruit vegetable crop worldwide with diverse morphological variation. We report a high-density genetic map of melon and nine major QTLs with physical region ranging from 43.47 kb to 1.89 Mb. Importantly, two seed-related trait QTLs were repeatedly detected in two environments, and the mapping region was narrowed to 522 kb according to a regional linkage analysis. A total of 40 annotated genes were screened for nonsynonymous variations, of which EVM0009818, involved in cytokinin-activated signaling, was differentially expressed in the young fruits of parents based on RNA-seq. Selective sweep analysis identified 152 sweep signals for seed size, including the two seed-related QTLs and nine homologs that have been verified to regulate seed size in Arabidopsis or rice. This work illustrates the power of a joint analysis combining resequencing-based genetic map for QTL mapping and a combination of KASP genotyping and RNA-seq analysis to facilitate QTL fine mapping.

Implementation and challenges to preventing the re-establishment of malaria in China in the COVID-19 era.

BACKGROUND: The rapid emergence and global spread of COVID-19 have caused substantial global disruptions that have impacted malaria programs worldwide. Innovative strategies to enable countries aiming to eliminate malaria as well as those that are already certified as malaria-free, are needed to address malaria importation in the context of the COVID-19 pandemic. China was certified as malaria-free in 2021 and now aims to prevent the malaria re-establishment. Nonpharmaceutical interventions such as entry screening, quarantining, and health education for individuals returning from international travel during the COVID-19 pandemic present both opportunities and challenges to the management of imported malaria. This study aimed to describe and analyze the operational challenges associated with an integrated surveillance and case management program in which malaria re-establishment prevention measures were incorporated into the COVID-19 program in China. METHODS: After the integration of malaria re-establishment prevention activities into the COVID-19 program for 10 months in Jiangsu Province, China, a focus-group discussion of public health workers working on preventing malaria re-establishment and controlling COVID-19 was held in June 2021, aiming to explore the operational challenges and lessons learned from the integrated approach. RESULTS: From 01 August 2020 to 31 May 2021, 8,947 overseas travelers with Yangzhou as the final destination underwent 14-day managed quarantine and 14-day home isolation. Of these travelers, 5,562 were from malaria-endemic regions. A total of 26,026 education booklets and materials were distributed to expand malaria-related knowledge. Twenty-two patients with unknown fever were screened for malaria with rapid diagnostic tests, and one patient was confirmed to have imported malaria. The challenges associated with the implementation of the integrated malaria surveillance and case management program include neglect of malaria due to COVID-19, lack of a standard operating procedure for malaria screening, mobility of public health providers, and difficulties in respecting the timeline of the "1-3-7" surveillance strategy. CONCLUSIONS: China's experience highlights the feasibility of integrated case surveillance and management of existing infectious diseases and new emerging infections. It also demonstrates the importance of a sound public health infrastructure with adequate, trained field staff for screening, testing, contact tracing, and providing health education, all of which are crucial for the success of both malaria re-establishment prevention program and the effective control of COVID-19.

A consensus and saturated genetic map provides insight into genome anchoring, synteny of Solanaceae and leaf- and fruit-related QTLs in wolfberry (Lycium Linn.).

BACKGROUND: Lycium Linn. (Solanaceae) is a genus of economically important plants producing fruits and leaves with high nutritional value and medicinal benefits. However, genetic analysis of this plant and molecular breeding for quality improvement are limited by the lack of sufficient molecular markers. RESULTS: In this study, two parental strains, 'Ningqi No. 1' (Lycium barbarum L.) and 'Yunnan Gouqi' (Lycium yunnanense Kuang et A.M. Lu), and 200 F1 hybrid individuals were resequenced for genetic analysis. In total, 8,507 well-selected SNPs were developed, and a high-density genetic map (NY map) was constructed with a total genetic distance of 2,122.24 cM. A consensus genetic map was established by integrating the NY map and a previously published genetic map (NC map) containing 15,240 SNPs, with a total genetic distance of 3,058.19 cM and an average map distance of 0.21 cM. The 12 pseudochromosomes of the Lycium reference genome were anchored using this consensus genetic map, with an anchoring rate of 64.3%. Moreover, weak collinearities between the consensus map and the pepper, potato, and tomato genomes were observed. Twenty-five stable QTLs were identified for leaf- and fruit-related phenotypes, including fruit weight, fruit longitude, leaf length, the fruit index, and the leaf index; these stable QTLs were mapped to four different linkage groups, with LOD scores ranging from 2.51 to 19.37 and amounts of phenotypic variance explained from 6.2% to 51.9%. Finally, 82 out of 188 predicted genes underlying stable QTLs for fruit-related traits were differentially expressed according to RNA-seq analysis. CONCLUSIONS: A chromosome-level assembly can provide a foundation for further functional genomics research for wolfberry. The genomic regions of these stably expressed QTLs could be used as targets for further fine mapping and development of molecular markers for marker-assisted selection (MAS). The present study provided valuable information on saturated SNP markers and reliable QTLs for map-based cloning of functional genes related to yield and morphological traits in Lycium spp.

Experimental realization of wavelength multiplexed nonlinear upconversion in cesium atoms.

Blue-violet wavelength multiplexing offers the capability to enhance the operational capacity and efficiency in optical information processing, underwater communications, biology, and medicine. Here we present a specially designed atomic scheme of cesium for simultaneously generating two blue-violet lasers at 456 and 459 nm via four-wave-mixing (FWM)-based upconversion processes. We experimentally and theoretically show that a double-diamond-type coherent system pumped with 852 and 921 nm lasers is responsible for the efficient generation of the two blue-violet lasers. In this system, the large population inversions lead to self-amplified spontaneous emissions at 15.6 and 12.1µm, which, in turn, serve as the seeds for enhanced double FWM processes with dual-wavelength upconversions.

Identification and characterization of a 25-lncRNA prognostic signature for early recurrence in hepatocellular carcinoma.

BACKGROUND: Early recurrence is the major cause of poor prognosis in hepatocellular carcinoma (HCC). Long non-coding RNAs (lncRNAs) are deeply involved in HCC prognosis. In this study, we aimed to establish a prognostic lncRNA signature for HCC early recurrence. METHODS: The lncRNA expression profile and corresponding clinical data were retrieved from total 299 HCC patients in TCGA database. LncRNA candidates correlated to early recurrence were selected by differentially expressed gene (DEG), univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses. A 25-lncRNA prognostic signature was constructed according to receiver operating characteristic curve (ROC). Kaplan-Meier and multivariate Cox regression analyses were used to evaluate the performance of this signature. ROC and nomogram were used to evaluate the integrated models based on this signature with other independent clinical risk factors. Gene set enrichment analysis (GSEA) was used to reveal enriched gene sets in the high-risk group. Tumor infiltrating lymphocytes (TILs) levels were analyzed with single sample Gene Set Enrichment Analysis (ssGSEA). Immune therapy response prediction was performed with TIDE and SubMap. Chemotherapeutic response prediction was conducted by using Genomics of Drug Sensitivity in Cancer (GDSC) pharmacogenomics database. RESULTS: Compared to low-risk group, patients in high-risk group showed reduced disease-free survival (DFS) in the training (p < 0.0001) and validation cohort (p = 0.0132). The 25-lncRNA signature, AFP, TNM and vascular invasion could serve as independent risk factors for HCC early recurrence. Among them, the 25-lncRNA signature had the best predictive performance, and combination of those four risk factors further improves the prognostic potential. Moreover, GSEA showed significant enrichment of "E2F TARGETS", "G2M CHECKPOINT", "MYC TARGETS V1" and "DNA REPAIR" pathways in the high-risk group. In addition, increased TILs were observed in the low-risk group compared to the high-risk group. The 25-lncRNA signature negatively associates with the levels of some types of antitumor immune cells. Immunotherapies and chemotherapies prediction revealed differential responses to PD-1 inhibitor and several chemotherapeutic drugs in the low- and high-risk group. CONCLUSIONS: Our study proposed a 25-lncRNA prognostic signature for predicting HCC early recurrence, which may guide postoperative treatment and recurrence surveillance in HCC patients.

Simulating the migration and species distribution of Cr and inorganic ions from tanneries in the vadose zone.

The pollution in soils and groundwater caused by the tannery have attracted public attention. However, few studies have been done on the migration and species distribution of Cr and coexisting ions produced by tanning in the vadose zone. In this paper, an in-production tannery and a suspended tannery were selected to compare the migration of Cr and other inorganic ions from tanneries in the vadose zone. Results showed that the sewage treatment station and the temporary waste storage site had the highest concentration of pollutants. Cr exhibited a cumulative effect in the middle soil layer (100-300 cm) in the suspended tannery. However, in the in-production tannery, the cumulative effect occurred only at the temporary waste storage site. The distribution of pollutants in the soils at different depths was fixed in the suspended tannery field. But in the in-production tannery field, it was closely related to daily production. Visual MINTEQ showed that the saturation index of a species of Cr was positive or negative simultaneously in the two sites, indicating that (1) the change of saturation index of Cr had no relationship with operation of tannery. (2) the influence of Cr precipitation or dissolution was related to the source strength, the coexisting ions, and pH. This study contributed to understanding the migration of characteristic pollutants caused by tanneries in the vadose zone under different external environments, and provided a reference for the quantification calculation of the source load of pollutants caused by industrial infiltration into the groundwater.

The natural product antroalbol H promotes phosphorylation of liver kinase B1 (LKB1) at threonine 189 and thereby enhances cellular glucose uptake.

Hypoglycemic drugs such as metformin increase glucose uptake and utilization by peripheral tissues to maintain glucose homeostasis, and the AMP-activated protein kinase (AMPK) signaling pathway is an important component of this pharmacological activity. Liver kinase B1 (LKB1) acts as a kinase upstream of AMPK and plays an important regulatory role in glucose metabolism. In recent years, as a tumor suppressor, LKB1's antitumor activity has been widely studied, yet its hypoglycemic activity is not clear. Here, using biochemical and cell viability assays, site-directed mutagenesis, immunoblotting, and immunofluorescence staining, we found that a natural product, antroalbol H isolated from the basidiomycete mushroom Antrodiella albocinnamomea, increases cellular glucose uptake in murine L6 myotubes and 3T3-L1 adipocytes. Of note, our results indicated that this effect is related to LKB1-mediated Thr-172 phosphorylation of AMPKα. Furthermore, we observed that antroalbol H induces the phosphorylation of LKB1 specifically at Thr-189 and changes subcellular localization of LKB1. Finally, antroalbol H treatment strikingly promoted glucose transporter type 4 (GLUT4) translocation to the plasma membrane. We conclude that antroalbol H promotes Thr-189 phosphorylation of LKB1, leading to AMPK activation, revealing this residue as a potential target for increasing glucose uptake, and that antroalbol H therefore has potential for managing hyperglycemia.

Treatment efficiency of comprehensive hysteroscopic evaluation and lesion resection combined with progestin therapy in young women with endometrial atypical hyperplasia and endometrial cancer.

OBJECTIVE: This study aimed to evaluate the efficacy of comprehensive hysteroscopic evaluation and lesion resection combined with progestin therapy in young patients with endometrial atypical hyperplasia (EAH) and early stage endometrial cancer (EEC) who wished to preserve their fertility. METHODS: Patients with EAH (n = 120) or well-differentiated EEC (n = 40, FIGO stage IA, without myometrial invasion) were retrospectively included. All patients received constant oral progestin combined with hysteroscopic evaluation every 3 months until achieving complete response (CR). The location, number and size of each suspected lesion or cluster were detailly recorded during the hysteroscopy. RESULTS: The median age was 32.0 year-old (range, 22-47 year-old). Totally 148 patients (97.4%) achieved CR while 3 EAH and 1 EEC patients presented with disease progression, and 8 patients were still in treatment. The mean treatment duration for achieving CR was 6.7 ±â€¯0.3 months (range, 1-18 months). After adjusting for patient age, body mass index (BMI), history of pregnancy and type of conservative therapies, lesion size ≤2 cm (OR, 0.701; 95% CI, 0.496-0.991; P = 0.045) was significantly correlated with shorter treatment time to achieve CR. Among 60 patients attempted to conceive after achieving CR, 45.0% (15/60) had been pregnant, 25.0% (15/60) delivered live birth, 13.3% (8/60) are still in pregnancy, while 6.7% experienced spontaneous abortion. CONCLUSION: Comprehensive hysteroscopic evaluation and lesion resection plus progestin therapy seem to be an effective and safe fertility sparing therapy for patients with EAH or EEC. Endometrial lesion size ≤2 cm correlated with a shorter treatment period to achieve CR.

Novel dual-color drug screening model for GLUT4 translocation in adipocytes.

Insulin-responsive glucose transporter type 4 (GLUT4) translocation plays a major role in controlling glucose uptake in adipose tissue and muscle, maintaining homeostasis and preventing hyperglycemia. Screening for chemicals enhancing GLUT4 translocation is an approach for identifying hits of drug development for type 2 diabetes. Here we developed a novel functional dual-color probe, pHluorin-GLUT4-mOrange2, and constructed 3T3-L1 adipocytes based screening system to simply and efficiently screen new compounds stimulating GLUT4 translocation. Based on this system, we successfully identified a few hits facilitating GLUT4 translocation. In conclusion, we developed an easy-to-apply dual color GLUT4 probe to monitor GLUT4 translocation in insulin-responsive cells, which could be alternatively employed to high-throughput screen compounds regulating GLUT4 translocation and glucose uptake, even to dissect GLTU4 approaching, docking and fusion with the plasma membrane (PM), and to reveal relevant molecular mechanisms involved in these steps as expected.

Five cases of uterine perivascular epithelioid cell tumors (PEComas) and review of literature.

OBJECTIVES: Perivascular epithelioid cell tumor (PEComa) is a rare condition and the recognition of this condition is limited. Here we report five cases of uterine PEComa to add to the limited understanding of this rare condition. METHODS: Five cases from Obstetrics and Gynecology Hospital of Fudan University were diagnosed as uterine PEComas. We collected the patients' clinical and pathological data as well as their outcomes. RESULTS: All the five cases were diagnosed post-operationally. Fertility-sparing surgery was done for the first case and had a mass resection only. She delivered a healthy boy through the cesarean section in November 2016 and neither recurrence nor metastasis was found for 71 months. Hysterectomy was done for the other four cases. Adjuvant chemotherapy was also given for case 2 and case 4. Case 2 had combined endometrial cancer, which could be associated with tuberous sclerosis complex (TSC). She was followed up for 22 months and neither recurrence nor metastasis was detected. Neither recurrence nor metastasis was found in case 3 for 33 months. However, the patient in case 4 died of multiple dissemination and multiple organs failures, 10 months after the second surgery. The patient in case 5 had the hysterectomy and left adnexal resection and in this case we had no data about her long-term outcomes. CONCLUSION: It is still challenging to detect and diagnose uterine PEComa clinically and no consensus or guidelines have been established regarding the treatment of this condition. More case studies are needed to enlighten the underlying mechanism and help optimize the therapies for this condition.

Adenanthin, a Natural ent-Kaurane Diterpenoid Isolated from the Herb Isodon adenantha Inhibits Adipogenesis and the Development of Obesity by Regulation of ROS.

Adenanthin, a natural ent-kaurane diterpenoid extracted from the herb Isodon adenantha, has been reported to increase intracellular reactive oxygen species in leukemic and hepatocellular carcinoma cells. However, the function and mechanism of the compound in adipogenesis and the development of obesity is still unknown. In this study, we demonstrated that adenanthin inhibited adipogenesis of 3T3-L1 and mouse embryonic fibroblasts, and the underlying mechanism included two processes: a delayed mitotic clonal expansion via G0/G1 cell cycle arrest by inhibiting the RB-E2F1 signaling pathway and a reduced C/EBPß signaling by inhibiting the expression and activity of C/EBPß during mitotic clonal expansion. Furthermore, adenanthin significantly reduced the growing body weight and adipose tissue mass during high-fat diet-inducing obesity of mice, indicating the beneficial effects of adenanthin as a potential agent for prevention of obesity.

In vivo evolution of drug-resistant Mycobacterium tuberculosis in patients during long-term treatment.

BACKGROUND: In the current scenario, the drug-resistant tuberculosis is a significant challenge in the control of tuberculosis worldwide. In order to investigate the in vivo evolution of drug-resistant M. tuberculosis, the present study envisaged sequencing of the draft genomes of 18 serial isolates from four pre-extensively drug-resistant (pre-XDR) tuberculosis patients for continuous genetic alterations. RESULTS: All of the isolates harbored single nucleotide polymorphisms (SNPs) ranging from 1303 to 1309 with M. tuberculosis H37Rv as the reference. SNPs ranged from 0 to 12 within patients. The evolution rates were higher than the reported SNPs of 0.5 in the four patients. All the isolates exhibited mutations at sites of known drug targets, while some contained mutations in uncertain drug targets including folC, proZ, and pyrG. The compensatory substitutions for rescuing these deleterious mutations during evolution were only found in RpoC I491T in one patient. Many loci with microheterogeneity showed transient mutations in different isolates. Ninety three SNPs exhibited significant association with refractory pre-XDR TB isolates. CONCLUSIONS: Our results showed evolutionary changes in the serial genetic characteristics of the pre-XDR TB patients due to accumulation of the fixed drug-resistant related mutations, and the transient mutations under continuous antibiotics pressure over several years.

miR-153 inhibits the migration and the tube formation of endothelial cells by blocking the paracrine of angiopoietin 1 in breast cancer cells.

The sprouting of endothelial cells is the first step of tumor angiogenesis. Our previous study suggests that miR-153 suppresses breast tumor angiogenesis partially through targeting hypoxia-induced factor (HIF1α). In this study, we demonstrated that miR-153 also suppresses the migration and the tube formation of endothelial cells through directly targeting angiopoietin 1 (ANG1) in breast cancer cells. There was a negative correlation between miR-153 and ANG1 levels in breast cancer. miR-153 blocked the expression and secretion of ANG1 in breast cancer cells through binding to ANG1 mRNA. Conditioned medium from the breast cancer cell, MCF7, treated with miR-153 had no effect on the proliferation of HUVECs, but significantly inhibited the migration and tube formation of HUVECs, which could be rescued by overexpression of ANG1. In addition, miR-153 also directly inhibited the proliferation and migration of MCF7 through downregulation of ANG1. These findings suggest that miR-153 suppresses the activity of tumor cells and the migration and tube formation of endothelial cells by silencing ANG1.

Prognostic Significance of Lymphovascular Space Invasion in the Absence of Lymph Node Metastases in Early-Stage Endometrial Cancer.

OBJECTIVE: Lymphovascular space invasion (LVSI) has been defined as a significant adverse prognostic factor in early-stage endometrial cancer, primarily because of its high association with nodal metastases. This study aimed to determine if LVSI provides any prognostic significance in pathologic node-negative surgically staged (T1N0) endometrial cancer patients. METHODS/MATERIALS: This retrospective cohort study included all patients with pathologic stage T1N0 endometrial carcinoma treated at The Ottawa Hospital Cancer Centre from 1998 to 2007. Patient demographics, pathologic findings, treatment, and outcome data were collected. Univariate and multivariate cox regression modeling was used to assess significance and adjust for demographic and histopathologic covariates. Kaplan-Meier curves were used to estimate the 5-year overall and recurrence-free survival. RESULTS: Our study included 400 pathologic stage T1N0 patients who received an initial total hysterectomy and bilateral salpingo-oophorectomy with lymphadenectomy. The median age at diagnosis was 62 years, and the median follow-up was 66 months. Fifty-four patients (13.5%) had a positive LVSI status, and 346 (86.5%) had a negative LVSI status. The 5-year overall survival was 97.3% in patients without LVSI and 90.9% in those with LVSI (P < 0.001). The 5-year recurrence-free survival was 95.2% in patients without LVSI and 85.9% in those with LVSI (P = 0.006). Univariate analysis identified grade, stage, and LVSI as the covariates significantly associated with time to recurrence, and identified age, grade, stage, and LVSI to be significantly associated with overall survival. There were no significant covariates for recurrence-free survival by multivariate analysis, and only age and LVSI were significant for overall survival. CONCLUSIONS: Lymphovascular space invasion is an overall poor prognostic factor in T1N0 endometrial cancer. After adjusting for other factors, LVSI remains an independent risk factor for worse overall survival. Therefore, estimation of overall survival in patients with early-stage, node-negative endometrial cancer should take into account LVSI status.