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Bisphenol S (BPS) is a typical endocrine disruptor associated with obesity. To observe BPS effects on lipid metabolism in HepG2 and SK-Hep-1 human HCC cells, a CCK-8 assay was used to assess cell proliferation in response to BPS, and the optimal concentration of BPS was selected. Biochemical indices such as triglyceride (TG) and total cholesterol (T-CHO), and oxidative stress indices such as malondialdehyde (MDA) and catalase (CAT) were measured. ROS and MDA levels were significantly increased after BPS treatment for 24 h and 48 h ( p < 0.05), indicating an oxidative stress response. Alanine aminotransferase (ALT), T-CHO, and low-density lipoprotein cholesterol (LDL-C) levels also increased significantly after 24 or 48 h BPS treatments ( p < 0.05). RT-PCR and Western blot analyses detected mRNA or protein expression levels of peroxisome proliferator-activated receptor α (PPARα) and sterol regulatory element-binding protein 1c (SREBP1C). The results indicated that BPS could inhibit the mRNA expression of PPARα and carnitine palmitoyl transferase 1B (CPT1B), reduce lipid metabolism, promote mRNA or protein expression of SREBP1C and fatty acid synthase (FASN), and increase lipid synthesis. Increased lipid droplets were observed using morphological Oil Red O staining. Our study demonstrates that BPS may cause lipid accumulation by increasing oxidative stress and perturbing cellular lipid metabolism.

During 25 surveys of global Phytophthora diversity, conducted between 1998 and 2020, 43 new species were detected in natural ecosystems and, occasionally, in nurseries and outplantings in Europe, Southeast and East Asia and the Americas. Based on a multigene phylogeny of nine nuclear and four mitochondrial gene regions they were assigned to five of the six known subclades, 2a-c, e and f, of Phytophthora major Clade 2 and the new subclade 2g. The evolutionary history of the Clade appears to have involved the pre-Gondwanan divergence of three extant subclades, 2c, 2e and 2f, all having disjunct natural distributions on separate continents and comprising species with a soilborne and aquatic lifestyle and, in addition, a few partially aerial species in Clade 2c; and the post-Gondwanan evolution of subclades 2a and 2g in Southeast/East Asia and 2b in South America, respectively, from their common ancestor. Species in Clade 2g are soilborne whereas Clade 2b comprises both soil-inhabiting and aerial species. Clade 2a has evolved further towards an aerial lifestyle comprising only species which are predominantly or partially airborne. Based on high nuclear heterozygosity levels ca . 38 % of the taxa in Clades 2a and 2b could be some form of hybrid, and the hybridity may be favoured by an A1/A2 breeding system and an aerial life style. Circumstantial evidence suggests the now 93 described species and informally designated taxa in Clade 2 result from both allopatric non-adaptive and sympatric adaptive radiations. They represent most morphological and physiological characters, breeding systems, lifestyles and forms of host specialism found across the Phytophthora clades as a whole, demonstrating the strong biological cohesiveness of the genus. The finding of 43 previously unknown species from a single Phytophthora clade highlight a critical lack of information on the scale of the unknown pathogen threats to forests and natural ecosystems, underlining the risk of basing plant biosecurity protocols mainly on lists of named organisms. More surveys in natural ecosystems of yet unsurveyed regions in Africa, Asia, Central and South America are needed to unveil the full diversity of the clade and the factors driving diversity, speciation and adaptation in Phytophthora . Taxonomic novelties: New species: Phytophthora amamensis T. Jung, K. Kageyama, H. Masuya & S. Uematsu, Phytophthora angustata T. Jung, L. Garcia, B. Mendieta-Araica, & Y. Balci, Phytophthora balkanensis I. Milenković, Ž. Tomić, T. Jung & M. Horta Jung, Phytophthora borneensis T. Jung, A. Durán, M. Tarigan & M. Horta Jung, Phytophthora calidophila T. Jung, Y. Balci, L. Garcia & B. Mendieta-Araica, Phytophthora catenulata T. Jung, T.-T. Chang, N.M. Chi & M. Horta Jung, Phytophthora celeris T. Jung, L. Oliveira, M. Tarigan & I. Milenković, Phytophthora curvata T. Jung, A. Hieno, H. Masuya & M. Horta Jung, Phytophthora distorta T. Jung, A. Durán, E. Sanfuentes von Stowasser & M. Horta Jung, Phytophthora excentrica T. Jung, S. Uematsu, K. Kageyama & C.M. Brasier, Phytophthora falcata T. Jung, K. Kageyama, S. Uematsu & M. Horta Jung, Phytophthora fansipanensis T. Jung, N.M. Chi, T. Corcobado & C.M. Brasier, Phytophthora frigidophila T. Jung, Y. Balci, K. Broders & I. Milenković, Phytophthora furcata T. Jung, N.M. Chi, I. Milenković & M. Horta Jung, Phytophthora inclinata N.M. Chi, T. Jung, M. Horta Jung & I. Milenković, Phytophthora indonesiensis T. Jung, M. Tarigan, L. Oliveira & I. Milenković, Phytophthora japonensis T. Jung, A. Hieno, H. Masuya & J.F. Webber, Phytophthora limosa H.-C. Zeng, H.-H. Ho, F.-C. Zheng & T. Jung, Phytophthora macroglobulosa H.-C. Zeng, H.-H. Ho, F.-C. Zheng & T. Jung, Phytophthora montana T. Jung, Y. Balci, K. Broders & M. Horta Jung, Phytophthora multipapillata T. Jung, M. Tarigan, I. Milenković & M. Horta Jung, Phytophthora multiplex T. Jung, Y. Balci, K. Broders & M. Horta Jung, Phytophthora nimia T. Jung, H. Masuya, A. Hieno & C.M. Brasier, Phytophthora oblonga T. Jung, S. Uematsu, K. Kageyama & C.M. Brasier, Phytophthora obovoidea T. Jung, Y. Balci, L. Garcia & B. Mendieta-Araica, Phytophthora obturata T. Jung, N.M. Chi, I. Milenković & M. Horta Jung, Phytophthora penetrans T. Jung, Y. Balci, K. Broders & I. Milenković, Phytophthora platani T. Jung, A. Pérez-Sierra, S.O. Cacciola & M. Horta Jung, Phytophthora proliferata T. Jung, N.M. Chi, I. Milenković & M. Horta Jung, Phytophthora pseudocapensis T. Jung, T.-T. Chang, I. Milenković & M. Horta Jung, Phytophthora pseudocitrophthora T. Jung, S.O. Cacciola, J. Bakonyi & M. Horta Jung, Phytophthora pseudofrigida T. Jung, A. Durán, M. Tarigan & M. Horta Jung, Phytophthora pseudoccultans T. Jung, T.-T. Chang, I. Milenković & M. Horta Jung, Phytophthora pyriformis T. Jung, Y. Balci, K.D. Boders & M. Horta Jung, Phytophthora sumatera T. Jung, M. Tarigan, M. Junaid & A. Durán, Phytophthora transposita T. Jung, K. Kageyama, C.M. Brasier & H. Masuya, Phytophthora vacuola T. Jung, H. Masuya, K. Kageyama & J.F. Webber, Phytophthora valdiviana T. Jung, E. Sanfuentes von Stowasser, A. Durán & M. Horta Jung, Phytophthora variepedicellata T. Jung, Y. Balci, K. Broders & I. Milenković, Phytophthora vietnamensis T. Jung, N.M. Chi, I. Milenković & M. Horta Jung, Phytophthora ×australasiatica T. Jung, N.M. Chi, M. Tarigan & M. Horta Jung, Phytophthora ×lusitanica T. Jung, M. Horta Jung, C. Maia & I. Milenković, Phytophthora ×taiwanensis Jung T, Milenković I, Balci Y, Janoušek J, Kudláček T, Nagy ZÁ, Baharuddin B, Bakonyi J, Broders KD, Cacciola SO, Chang T-T, Chi NM, Corcobado T, Cravador A, Đorđević B, Durán A, Ferreira M, Fu C-H, Garcia L, Hieno A, Ho H-H, Hong C, Junaid M, Kageyama K, Kuswinanti T, Maia C, Májek T, Masuya H, Magnano di San Lio G, Mendieta-Araica B, Nasri N, Oliveira LSS, Pane A, Pérez-Sierra A, Rosmana A, Sanfuentes von Stowasser E, Scanu B, Singh R, Stanivuković Z, Tarigan M, Thu PQ, Tomić Z, Tomšovský M, Uematsu S, Webber JF, Zeng H-C, Zheng F-C, Brasier CM, Horta Jung M (2024). Worldwide forest surveys reveal forty-three new species in Citation: Jung T, Milenković I, Balci Y, Janoušek J, Kudláček T, Nagy ZÁ, Baharuddin B, Bakonyi J, Broders KD, Cacciola SO, Chang T-T, Chi NM, Corcobado T, Cravador A, Đorđević B, Durán A, Ferreira M, Fu C-H, Garcia L, Hieno A, Ho H-H, Hong C, Junaid M, Kageyama K, Kuswinanti T, Maia C, Májek T, Masuya H, Magnano di San Lio G, Mendieta-Araica B, Nasri N, Oliveira LSS, Pane A, Pérez-Sierra A, Rosmana A, Sanfuentes von Stowasser E, Scanu B, Singh R, Stanivuković Z, Tarigan M, Thu PQ, Tomić Z, Tomšovský M, Uematsu S, Webber JF, Zeng H-C, Zheng F-C, Brasier CM, Horta Jung M (2024). Worldwide forest surveys reveal forty-three new species in Phytophthora major Clade 2 with fundamental implications for the evolution and biogeography of the genus and global plant biosecurity. Studies in Mycology 107 : 251-388. doi: 10.3114/sim.2024.107.04., Competing Interests: The authors declare that there is no conflict of interest., (© 2023 Westerdijk Fungal Biodiversity Institute.)

In-plane sulfur vacancies (Sv) in molybdenum disulfide (MoS 2 ) were newly unveiled for CO 2 hydrogenation to methanol, whereas edge Sv were found to facilitate methane formation. Thus, selective exposure and activation of basal plane is crucial for methanol synthesis. Here, we report a mesoporous silica-encapsulated MoS 2 catalysts with fullerene-like structure and atomic copper (Cu/MoS 2 @SiO 2 ). The main approach is based on a physically constrained topologic conversion of molybdenum dioxide (MoO 2 ) to MoS 2 within silica. The spherical curvature enables the generation of strain and Sv in inert basal plane. More importantly, fullerene-like structure of few-layer MoS 2 can selectively expose in-plane Sv and reduce the exposure of edge Sv. After promotion by atomic copper, the resultant Cu/MoS 2 @SiO 2 exhibits stable specific methanol yield of 6.11 mol MeOH  mol Mo -1  h -1 with methanol selectivity of 72.5% at 260 °C, much superior to its counterparts lacking the fullerene-like structure and copper decoration. The reaction mechanism and promoting role of copper are investigated by in-situ DRIFTS and in-situ XAS. Theoretical calculations demonstrate that the compressive strain facilitates Sv formation and CO 2 hydrogenation, while tensile strain accelerates the regeneration of active sites, rationalizing the critical role of strain., (© 2023. Springer Nature Limited.)

Bimetallic nanoparticle (NP) catalysts are widely used in many heterogeneous gas-based reactions because they often outperform their monometallic counterparts. During these reactions, NPs often undergo structural changes, which impact their catalytic activity. Despite the important role of the structure in the catalytic activity, many aspects of how a reactive gaseous environment affects the structure of bimetallic nanocatalysts are still lacking. Here, using gas-cell transmission electron microscopy (TEM), it is shown that during a CO oxidation reaction over PdCu alloy NPs, the selective oxidation of Cu causes the segregation of Cu and transforms the NPs into Pd-CuO NPs. The segregated NPs are very stable and have high activity for the conversion of CO into CO 2 . Based on the observations, the segregation of Cu from Cu-based alloys during a redox reaction is likely to be general and may have a positive impact on the catalytic activity. Hence, it is believed that similar insights based on direct observation of the reactions under relevant reactive conditions are critical both for understanding and designing high-performance catalysts., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Bisphenol S (BPS) is an environmental pollutant that can accumulate in the human body and cause harm. Puerarin (PUE) is a flavonoid with anti-inflammatory and antioxidant effects. In this study, we used 50 mg/kg/d BPS as a poison and PUE as an intervention for model mice for 42 d. BPS exposure significantly increased the levels of the impairment of the mice's liver function, T-CHO, TG, LDL-C, ALT, and AST in the BPS group were significantly increased ( p < 0.05). Additionally, BPS exposure caused inflammatory cell infiltration in the mice liver tissue and enhanced oxidative stress response, the level of MDA was significantly increased ( p < 0.05). The expression of CD36 and pparγ was stimulated after BPS exposure. Moreover, the expression of cpt1a and cpt1b, which promote fatty acid oxidation, was downregulated. After PUE intervention, the levels of genes and proteins involved in lipid synthesis (PPARγ, SREBP1C, and FASN) and metabolism (Cpt1a, Cpt1b, and PPARα) in mice returned to those of the control group, or much higher than those in the BPS group. Therefore, we hypothesized that BPS causes lipid accumulation in the liver by promoting lipid synthesis and reducing lipid metabolism, whereas PUE reduces lipid synthesis and promotes lipid metabolism. Conclusively, our results imply that long-term exposure to BPS in mice affects liver lipid metabolism and that PUE intervention could maintain the liver function of mice at normal metabolic levels.

Bisphenol S (BPS), the most common substitute for bisphenol A in manufacturing, is associated with neurotoxicity, but its molecular mechanisms are unclear. Here, we studied the role of the BDNF-TrkB-CREB (brain-derived neurotrophic factor-tropomyosin-related kinase B-CAMP response element-binding protein) signalling pathway in bisphenol S-induced neurotoxicity via methylation regulation in male C57BL/6 mice. The mice were treated with sesame oil or 2, 20 and 200 mg/kg body weight BPS for 28 consecutive days, and the hippocampus was extracted. We recorded the body weight, organ index, and hippocampal pathology and ultrastructure of the mice. The BDNF, TrkB, CREB, phosphorylated (p)-CREB, DNMTs (DNA methyltransferases) levels were determined by qRT-PCR and/or Western blotting. BDNF promoter IV methylation level was detected by bisulfite sequencing PCR. BPS damaged the mouse hippocampus ultrastructure and reduced the number of synapses. Further, it increased the methylation rate of BDNF promoter IV; downregulated BDNF, CREB, p-CREB/CREB and DNMT1 expression; and upregulated DNMT3a and DNMT3b expression. Therefore, we speculate that the BDNF-TrkB-CREB pathway may be involved in BPS-induced neurotoxicity in male mice by regulating methylation.

The expression of microRNAs (miRNAs) is dysregulated in many types of cancers including osteosarcoma (OS) due to genetic and epigenetic alterations. Among these, miR-34c , an effector of tumor suppressor P53 and an upstream negative regulator of Notch signaling in osteoblast differentiation, is dysregulated in OS. Here, we demonstrated a tumor suppressive role of miR-34c in OS progression using in vitro assays and in vivo genetic mouse models. We found that miR-34c inhibits the proliferation and the invasion of metastatic OS cells, which resulted in reduction of the tumor burden and increased overall survival in an orthotopic xenograft model. Moreover, the osteoblast-specific overexpression of miR-34c increased survival in the osteoblast specific p53 mutant OS mouse model. We found that miR-34c regulates the transcription of several genes in Notch signaling ( NOTCH1 , JAG1 , and HEY2 ) and in p53-mediated cell cycle and apoptosis ( CCNE2 , E2F5 , E2F2 , and HDAC1 ). More interestingly, we found that the metastatic-free survival probability was increased among a patient cohort from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) OS, which has lower expression of direct targets of miR-34c that was identified in our transcriptome analysis, such as E2F5 and NOTCH1 . In conclusion, we demonstrate that miR-34c is a tumor suppressive miRNA in OS progression in vivo . In addition, we highlight the therapeutic potential of targeting miR-34c in OS. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research., Competing Interests: The authors declare no competing financial interests., (© 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.)

Purpose: The basic helix-loop-helix transcription factor (bHLH) transcription factor Twist1 plays a key role in embryonic development and tumorigenesis. p53 is a frequently mutated tumor suppressor in cancer. Both proteins play a key and significant role in breast cancer tumorigenesis. However, the regulatory mechanism and clinical significance of their co-expression in this disease remain unclear. The purpose of this study was to analyze the expression patterns of p53 and Twist1 and determine their association with patient prognosis in breast cancer. We also investigated whether their co-expression could be a potential marker for predicting patient prognosis in this disease., Methods: Twist1 and mutant p53 expression in 408 breast cancer patient samples were evaluated by immunohistochemistry. Kaplan-Meier Plotter was used to analyze the correlation between co-expression of Twist1 and wild-type or mutant p53 and prognosis for recurrence-free survival (RFS) and overall survival (OS). Univariate analysis, multivariate analysis, and nomograms were used to explore the independent prognostic factors in disease-free survival (DFS) and OS in this cohort., Results: Of the 408 patients enrolled, 237 (58%) had high mutant p53 expression. Two-hundred twenty patients (53.9%) stained positive for Twist1, and 188 cases were Twist1-negative. Furthermore, patients that co-expressed Twist1 and mutant p53 (T+P+) had significantly advanced-stage breast cancer [stage III, 61/89 T+P+ (68.5%) vs. 28/89 T-P- (31.5%); stage II, 63/104 T+P+ (60.6%) vs. 41/104 T-P- (39.4%)]. Co-expression was negatively related to early clinical stage (i.e., stages 0 and I; P = 0.039). T+P+ breast cancer patients also had worse DFS (95% CI = 1.217-7.499, P = 0.017) and OS ( 95% CI = 1.009-9.272, P = 0.048). Elevated Twist1 and mutant p53 expression predicted shorter RFS in basal-like patients. Univariate and multivariate analysis identified three variables (i.e., lymph node involvement, larger tumor, and T+P+) as independent prognostic factors for DFS. Lymph node involvement and T+P+ were also independent factors for OS in this cohort. The total risk scores and nomograms were reliable for predicting DFS and OS in breast cancer patients., Conclusions: Our results revealed that co-expression of mutant p53 and Twist1 was associated with advanced clinical stage, triple negative breast cancer (TNBC) subtype, distant metastasis, and shorter DFS and OS in breast cancer patients. Furthermore, lymph nodes status and co-expression of Twist1 and mutant p53 were classified as independent factors for DFS and OS in this cohort. Co-evaluation of mutant p53 and Twist1 might be an appropriate tool for predicting breast cancer patient outcome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Zhang, Zeng, Chen, Huang, Wu, Chen, Gao, Bai, Yang, Zeng, Wei and Zhang.)

The liver is the primary target organ for perfluorooctane sulphonate (PFOS), a recently discovered persistent organic pollutant. However, the mechanisms mediating hepatotoxicity remain unclear. Herein, we explored the relationship between reactive oxygen species (ROS) and autophagy and apoptosis induced by PFOS in L-02 cells, which are incubated with different concentrations of PFOS (0, 50, 100, 150, 200, or 250  μ mol/L) for 24 or 48 hrs at 37°C. The results indicated that PFOS exposure decreased cell activities, enhanced ROS levels in a concentration-dependent manner, decreased mitochondrial membrane potential (MMP), and induced autophagy and apoptosis. Compared with the control, 200  μ mol/L PFOS increased ROS levels; enhanced the expression of Bax, cleaved-caspase-3, and LC3-II; induced autophagy; decreased MMP; and lowered Bcl-2, p62, and Bcl-2/Bax ratio. The antioxidant N-acetyl cysteine (NAC) protected MMP against PFOS-induced changes and diminished apoptosis and autophagy. Compared with 200  μ mol/L PFOS treatment, NAC pretreatment reversed the increase in ROS, Bax, and cleaved-caspase-3 protein caused by PFOS, lowered the apoptosis rate increased by PFOS, and increased the levels of MMP and Bcl-2/Bax ratio decreased by PFOS. The autophagy inhibitor 3-methyladenine and chloroquine decreased apoptosis and cleaved-caspase-3 protein level and increased the Bcl-2/Bax ratio. In summary, our results suggest that ROS-triggered autophagy is involved in PFOS-induced apoptosis in L-02 cells., Competing Interests: The authors have no conflict of interests to declare regarding the publication of this work., (Copyright © 2021 Huai-cai Zeng et al.)

The prevalence of mitral valve prolapse (MVP) among middle- and older-aged individuals is estimated to be 2-4% in Western countries. However, few studies have been conducted among Asian individuals and young adults. This study included a sample of 2442 consecutive military adults aged 18-39 years in Hualien, Taiwan. MVP was defined as displacement of the anterior or posterior leaflet of the mitral valve to the mid portion of the annular hinge point > 2 mm in the parasternal long-axis view of echocardiography. Cardiac chamber size and wall thickness were measured based on the latest criteria of the American Society of Echocardiography. The clinical features of participants with MVP and those without MVP were compared using a two-sample t test, and the cardiac structures were compared using analysis of covariance with adjustment for body surface area (BSA). Eighty-two participants were diagnosed with MVP, and the prevalence was 3.36% in the overall population. Compared with those without MVP, participants with MVP had a lower body mass index (kg/m 2 ) (24.89 ± 3.70 vs. 23.91 ± 3.45, p = 0.02) and higher prevalence of somatic symptoms related to exercise (11.0% vs. 4.9%, p = 0.02) and systolic click in auscultation (18.3% vs. 0.6%, p < 0.01). In addition, participants with MVP had greater left ventricular mass (gm) and smaller right ventricular wall thickness (mm) and dimensions (mm) indexed by BSA than those without MVP (149.12 ± 35.76 vs. 155.38 ± 36.26; 4.66 ± 0.63 vs. 4.40 ± 0.68; 26.57 ± 3.99 vs. 25.41 ± 4.35, respectively, all p-values < 0.01). In conclusion, the prevalence and clinical features of MVP in military young adults in Taiwan were in line with those in Western countries. Whether the novel MVP phenotype found in this study has any pathological meaning needs further investigation.

Ulcerative colitis (UC) is the most common inflammatory bowel disease, and its incidence has increased in recent years. Recent clinical and experimental data indicate that gut microbiota plays a pivotal role in the pathogenesis of UC. Chlamydia establishes a stable and persistent colonization in the gastrointestinal tract without apparent pathogenicity to gastrointestinal or extragastrointestinal tissues. However, the detailed effects of Chlamydia on the gastrointestinal tissue remain unknown. The primary aim of this study is to investigate the effects of Chlamydia muridarum ( C. muridarum ) on development of colitis induced by dextran sodium sulfate (DSS) and the underlying molecular mechanism. The results suggested that C. muridarum significantly improved colitis symptoms-including weight loss, disease activity index, colon length, and histopathological changes in the colon caused by DSS-and alleviated the reduced expression of interleukin-22 and occludin in the colonic tissue due to DSS administration. Furthermore, the absence of IL-22 completely prevented C. muridarum from alleviating colitis and significantly decreased the levels of occludin, an important downstream effector protein of IL-22. These findings suggest that C. muridarum ameliorates ulcerative colitis induced by DSS via the IL-22/occludin signal pathway., Competing Interests: The authors have no conflict of interests to declare regarding the publication of this paper., (Copyright © 2020 Xin Wang et al.)

Axillary reverse mapping (ARM) is a technique to identify arm lymphatic drainage during axillary lymph node dissection (ALND). This study compared the feasibility of ARM using indocyanine green (ICG) or methylene blue (MB), and accessed the oncologic safety of the procedure. Overall, 158 patients qualified for ALND were enrolled. The characteristics of ARM-identified nodes were recorded with ICG (n = 78) or MB (n = 80) visualization. Fine-needle aspiration cytology (FNAC) of the nodes were performed and validated by histologic analysis. The nodal identification rate in the ICG group significantly surpassed that of the MB group (87.2% vs 52.5%, P  < .05) with fewer complications. Note that 10.9% of the patients had metastatic involvement of the ARM-identified nodes. Also 80% of the positive nodes were found in areas B and D, while the ARM-identified nodes mainly located in area A. All the 51 nodes diagnosed as negative of malignancy by FNAC were free of metastasis. Nodal metastasis was significantly correlated with extensive nodel involvement, advanced disease, and the characteristics of identified nodes. In conclusion, ICG appears superior to MB for ARM nodes identification. FNAC, together with the features of primary tumors and ARM nodes, can delineate which nodes could be preserved during ALND., Competing Interests: The authors declared no conflict of interest., (© 2020 The Authors. MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.)

Background: Earlier studies have suggested that microtia is a genetic disease with a worldwide incidence of microtia is between 0.83/10,000 and 17.40/10,000. For microtia, auricle morphology is the most crucial characteristic. However, no studies have been performed to characterize the genetic similarity of microtia and auricle morphology similarity. For the sporadic patients, the relationship between the gestational age of parents and the incidence of microtia is unclear. To obtain the characteristics of auricular deformity multiple case family (AD-MCF) and clarify the relationship between genetic similarity and auricle morphology similarity in AD-MCF., Methods: This study included 463 AD patients who were diagnosed by Sun Yat-sen Memorial Hospital, Sun Yat-sen University, from 2013 to 2019. Among these patients, 116 are from 43 MCF and the other 347 patients are sporadic. For the patients from families, the disease status of the four generations of immediate family members and the family tree map were collected to analyze the similarity of auricle shape in family members. A score evaluated the similarity of auricle shape according to the structure of the residual ear and the similarity in the morphology of each auricle. Moreover, the population distribution of AD and the gestational age of patients were further analyzed., Results: From 2013 to 2019, a total of 463 patients were diagnosed as microtia in our hospital. There were 427 patients with unilateral disease and 36 patients with bilateral disease. Among them, 116 patients were from 34 families and 9 de novo families. The total scores of patients in different genetic difference levels were compared and were found significantly different (P<0.001). Moreover, 58.14% of families were consistent with the law of chromosomal recessive genetic diseases. Importantly, we found that the gestational age of father in microtia de novo families is 30.94±0.75, and mother in de novo is 28.39±0.73 that is significantly higher than the gestational ages of parents from microtia families with P value =0.0001., Conclusions: The auricle similarity between family members is positively related to the genetic distance between family members. The microtia patients are potentially associated with the gestational ages of parents., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm.2020.03.212). The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

Formation mechanisms of two-dimensional nanostructures in wet syntheses are poorly understood. Even more enigmatic is the influence of hydrodynamic forces. Here we use liquid flow cell transmission electron microscopy to show that layered double hydroxide, as a model material, may form via the oriented attachment of hexagonal nanoparticles; under hydrodynamic shear, oriented attachment is accelerated. To hydrodynamically manipulate the kinetics of particle growth and oriented attachment, we develop a microreactor with high and tunable shear rates, enabling control over particle size, crystallinity and aspect ratio. This work offers new insights in the formation of two-dimensional materials, provides a scalable yet precise synthesis method, and proposes new avenues for the rational engineering and scalable production of highly anisotropic nanostructures.

Interactions between metal nanoparticles (NPs) and metal-organic frameworks (MOFs) in their composite forms have proven to exhibit beneficial properties, such as enhanced catalytic performance through synergistic effects. Herein, we show that Lewis basic sites can be created within an anionic defective MOF by engineering the electronic state of the pendant carboxylate groups situated at the defect sites. This is achieved from the concerted interactions between the pendant carboxylate groups, embedded Pd NPs and charge-balancing cations (M n+  = Ce 3+ , Co 2+ , Ni 2+ , Cu 2+ , Mg 2+ , Li + , Na + or K + ). This work is the first example of generating a new collective property, i.e. Lewis basicity, in metal-carboxylate MOFs. Importantly, the choice of M n+ , used during cation exchange, acts as a convenient parameter to tune the Lewis basicity of the MOF-based nanocomposites. It also provides a facile way to incorporate active metal sites and basic sites within carboxylate-based MOFs to engineer multifunctional nanocatalysts.

Hydrogen spillover phenomenon is well-documented in hydrogenation catalysis but still highly disputed in hydrogen storage. Until now, the existence of hydrogen spillover through metal-organic frameworks (MOFs) remains a topic of ongoing debate and how far the split hydrogen atoms diffuse in such materials is unknown. Herein we provide experimental evidence of the occurrence of hydrogen spillover in microporous MOFs at elevated temperatures, and the penetration depths of atomic hydrogen were measured quantitatively. We have made Matryoshka-type (ZIFs@) n-1 ZIFs (where ZIFs = ZIF-8 or ZIF-67) nanocubes, together with Pt nanoparticles loaded on their external surfaces to produce atomic hydrogen. Within the (ZIFs@) n-1 ZIFs, the ZIF-8 shell served as a ruler to measure the travelling distance of H atoms while the ZIF-67 core as a terminator of H atoms. In addition to the hydrogenolysis at normal pressure, CO 2 hydrogenation can also trace the migration of H atoms over the ZIF-8 at high pressure.

Particulate catalysts with streamline shapes have important impacts on fluid-related reactions, and they need to be properly characterized. However, utilization of streamline-shaped catalysts for heterogeneous catalysis has remained an unexplored area due to the lack of easy-to-use techniques to produce such shaped catalysts, especially at the small length scale of the submicron to micron regime. Herein, we report our recent development of a class of prototype nanocatalysts with streamline shapes. In this research, the kinetic control is adapted to obtain streamline-shaped supports, followed by functionalizing such supports with catalytically active metal nanoclusters (e.g., Au, Pd, Pt, and Ag or their combinations) in a stepwise manner. Advantages related to the streamline morphology of catalysts have been demonstrated with a number of solid-solution systems such as alcohol oxidation, olefin hydrogenation, and Suzuki-Miyaura coupling. We believe these findings will promote new research on the design and synthesis of functional materials with additional fluid-advanced features.

Perfluorooctane sulfonate (PFOS), a new kind of persistent organic pollutant, is widely distributed in the environment and exists in various organisms, where it is also a neurotoxic compound. However, the potential mechanism of its neurotoxicity is still unclear. To examine the role of epigenetics in the neurotoxicity induced by PFOS, SK-N-SH cells were treated with different concentrations of PFOS or control medium (0.1% DMSO) for 48 h. The mRNA levels of DNA methyltransferases (DNMTs) and Brain-derived neurotrophic factor (BDNF), microRNA-16, microRNA-22, and microRNA-30a-5p were detected by Quantitative PCR (QPCR). Enzyme Linked Immunosorbent Assay (ELISA) was used to measure the protein levels of BDNF, and a western blot was applied to analyze the protein levels of DNMTs. Bisulfite sequencing PCR (BSP) was used to detect the methylation status of the BDNF promoter I and IV. Results of MTT assays indicated that treatment with PFOS could lead to a significant decrease of cell viability, and the treated cells became shrunk. In addition, PFOS exposure decreased the expression of BDNF at mRNA and protein levels, increased the expression of microRNA-16, microRNA-22, microRNA-30a-5p, and decreased the expression of DNMT1 at mRNA and protein levels, but increased the expression of DNMT3b at mRNA and protein levels. Our results also demonstrate that PFOS exposure changes the methylation status of BDNF promoter I and IV. The findings of the present study suggest that methylation regulation of BDNF gene promoter and increases of BDNF-related-microRNA might underlie the mechanisms of PFOS-induced neurotoxicity.

Osteocytes are the terminally differentiated cell type of the osteoblastic lineage and have important functions in skeletal homeostasis. Although the transcriptional regulation of osteoblast differentiation has been well characterized, the factors that regulate differentiation of osteocytes from mature osteoblasts are poorly understood. Here we show that miR-23a∼27a∼24-2 (miR-23a cluster) promotes osteocyte differentiation. Osteoblast-specific miR-23a cluster gain-of-function mice have low bone mass associated with decreased osteoblast but increased osteocyte numbers. By contrast, loss-of-function transgenic mice overexpressing microRNA decoys for either miR-23a or miR-27a, but not miR24-2, show decreased osteocyte numbers. Moreover, RNA-sequencing analysis shows altered transforming growth factor-β (TGF-β) signalling. Prdm16, a negative regulator of the TGF-β pathway, is directly repressed by miR-27a with concomitant alteration of sclerostin expression, and pharmacological inhibition of TGF-β rescues the phenotypes observed in the gain-of-function transgenic mice. Taken together, the miR-23a cluster regulates osteocyte differentiation by modulating the TGF-β signalling pathway through targeting of Prdm16.

Based on the terrain observation by progressive scans (TOPS) mode, an efficient full-aperture image formation algorithm for focusing wide-swath spaceborne TOPS data is proposed. First, to overcome the Doppler frequency spectrum aliasing caused by azimuth antenna steering, the range-independent derotation operation is adopted, and the signal properties after derotation are derived in detail. Then, the azimuth deramp operation is performed to resolve image folding in azimuth. The traditional dermap function will introduce a time shift, resulting in appearance of ghost targets and azimuth resolution reduction at the scene edge, especially in the wide-swath coverage case. To avoid this, a novel solution is provided using a modified range-dependent deramp function combined with the chirp-z transform. Moreover, range scaling and azimuth scaling are performed to provide the same azimuth and range sampling interval for all sub-swaths, instead of the interpolation operation for the sub-swath image mosaic. Simulation results are provided to validate the proposed algorithm., Competing Interests: The authors declare no conflict of interest.

Objective: To observe the effect of RITA, a small molecule that targets p53, combined with temozolomide (TMZ) on proliferation, colony formation and apoptosis of human glioblastoma U87 cells and explore the underlying mechanism., Methods: Cultured U87 cells were treated with RITA (1, 5, 10, 20 µmol/L), TMZ, or RITA+TMZ (half dose) for 24, 48 or 72 h. MTS assay were used to detect the cell proliferation, and the cell proliferation rate and inhibitory rate were calculated. The effect of combined treatments was evaluated by the q value. The expressions of p53, p21 and other apoptosis-associated genes were detected by qRT-PCR and Western blotting; cell apoptosis was assayed using flow cytometry with Annexin V/PI double staining; colony formation of the cells was detected with crystal violet staining., Results: MTS assay showed that RITA at the 4 doses more potently inhibited U87 cell viability than TMZ at 72 h (P=0.000) with inhibitory rates of 25.94%-41.38% and 3.84%-8.20%, respectively. RITA combined with TMZ caused a more significant inhibition of U87 cells (29.21%-52.11%) than RITA (P<0.01) and TMZ (P=0.000) alone. At the doses above 5 µmol/L, the combined treatments with RITA+TMZ for 48 h resulted in q values exceeding 1.2 and showed an obvious synergistic effect of the drugs. Both RITA and TMZ, especially the latter, significantly increased the expressions of p53, p21, puma, and other apoptosis-associated genes to accelerate apoptosis and inhibit the growth and colony formation of U87 cells, and the effect was more obvious with a combined treatment., Conclusion: RITA inhibits the growth of human glioblastoma cells and enhance their sensitivity to TMZ by up-regulating p53 expression, and when combined, RITA and TMZ show a synergistic effect to cause a stronger cell inhibition.

Papaya ringspot virus (PRSV) severely affects the global papaya industry. Transgenic papaya has been proven to have effective resistance to PRSV isolates from Hawaii, Thailand, Taiwan, and other countries. However, those transgenic cultivars failed to show resistance to Hainan Island isolates. Some 76 PRSV samples, representative of all traditional papaya planting areas across five cities (Wen Chang, n = 13; Cheng Mai, n = 14; Chang Jiang, n = 11; Le Dong, n = 25; and San Ya, n = 13) within Hainan Province, were investigated. Results revealed three genetic diversity groups (Hainan I, II, and III) that correlated with geographical distribution. Frequent mutations among PRSV isolates from Hainan were also observed. The high genetic divergence in PRSV isolates from Hainan is likely to be the cause of the failure of genetically modified papaya that targets sequence-specific virus.

Global Navigation Satellite System (GNSS)-based bistatic Synthetic Aperture Radar (SAR) recently plays a more and more significant role in remote sensing applications for its low-cost and real-time global coverage capability. In this paper, a general imaging formation algorithm was proposed for accurately and efficiently focusing GNSS-based bistatic SAR data, which avoids the interpolation processing in traditional back projection algorithms (BPAs). A two-dimensional point target spectrum model was firstly presented, and the bulk range cell migration correction (RCMC) was consequently derived for reducing range cell migration (RCM) and coarse focusing. As the bulk RCMC seriously changes the range history of the radar signal, a modified and much more efficient hybrid correlation operation was introduced for compensating residual phase errors. Simulation results were presented based on a general geometric topology with non-parallel trajectories and unequal velocities for both transmitter and receiver platforms, showing a satisfactory performance by the proposed method.

Among patients with a preoperative positive axillary ultrasound, around 40% of them are pathologically proved to be free from axillary lymph node (ALN) metastasis. We aimed to develop and validate a model to predict the probability of ALN metastasis as a preoperative tool to support clinical decision-making. Clinicopathological features of 322 early breast cancer patients with positive axillary ultrasound findings were analyzed. Multivariate logistic regression analysis was performed to identify independent predictors of ALN metastasis. A model was created from the logistic regression analysis, comprising lymph node transverse diameter, cortex thickness, hilum status, clinical tumour size, histological grade and estrogen receptor, and it was subsequently validated in another 234 patients. Coefficient of determination (R(2)) and the area under the ROC curve (AUC) were calculated to be 0.9375 and 0.864, showing good calibration and discrimination of the model, respectively. The false-negative rates of the model were 0% and 5.3% for the predicted probability cut-off points of 7.1% and 13.8%, respectively. This means that omission of axillary surgery may be safe for patients with a predictive probability of less than 13.8%. After further validation in clinical practice, this model may support increasingly limited surgical approaches to the axilla in breast cancer.

In this work, the staggered SAR technique is employed for high-speed platform highly-squint SAR by varying the pulse repetition interval (PRI) as a linear function of range-walk. To focus the staggered SAR data more efficiently, a low-complexity modified Omega-k algorithm is proposed based on a novel method for optimal azimuth non-uniform interpolation, avoiding zero padding in range direction for recovering range cell migration (RCM) and saving in both data storage and computational load. An approximate model on continuous PRI variation with respect to sliding receive-window is employed in the proposed algorithm, leaving a residual phase error only due to the effect of a time-varying Doppler phase caused by staggered SAR. Then, azimuth non-uniform interpolation (ANI) at baseband is carried out to compensate the azimuth non-uniform sampling (ANS) effect resulting from continuous PRI variation, which is further followed by the modified Omega-k algorithm. The proposed algorithm has a significantly lower computational complexity, but with an equally effective imaging performance, as shown in our simulation results.

Chlamydophila psittaci (C. psittaci) is a human zoonotic pathogen, which could result in severe respiratory disease. In the present study, we investigated the role and mechanism of the type III secretion system (T3SS) of C. psittaci in regulating the inflammatory response in host cells. C. psittaci-infected THP-1 cells were incubated with the specific T3SS inhibitor INP0007, inhibitors of ERK, p38, or JNK, and the levels of inflammatory cytokines were analyzed using Q-PCR and ELISA. The levels of ERK, p38, and JNK phosphorylation were analyzed by Western blot. Our results verified that INP0007 inhibited chlamydial growth in vitro, but the coaddition of exogenous iron completely reversed the growth deficit. INP0007 inhibited the growth of C. psittaci and decreased the levels of IL-8, IL-6, TNF-α, and IL-1β. Exogenous iron restored the chlamydial growth but not the production of inflammatory cytokines. These results demonstrated that the expression of inflammatory cytokines during infection was associated with the T3SS which reduced by incubation with ERK and JNK inhibitors, but not with p38 inhibitor. We concluded that the T3SS elicited inflammatory responses by activating the JNK or ERK signaling pathways in the infection of C. psittaci.

Perfluorooctane sulfonate (PFOS), a ubiquitous environmental pollutant, is neurotoxic to mammalian species. However, the underlying mechanism of its neurotoxicity was unclear. We hypothesized that PFOS suppresses BDNF expression to produce its neurotoxic effects by inhibiting the ERK-CREB pathway. SH-SY5Y human neuroblastoma cells were exposed to various concentrations of PFOS to examine the role of the BDNF-ERK-CREB signalling pathway in PFOS-induced apoptosis and cytotoxicity. Furthermore, to ascertain the mechanism by which PFOS reduces BDNF signalling, we examined the expression levels of miR-16 and miR-22, which potentially regulate BDNF mRNA translation at the posttranscriptional level. Results indicated that PFOS significantly decreased cell viability and induced apoptosis in SH-SY5Y cells. In addition, BDNF and pERK protein levels decreased after PFOS treatment; however, pCREB protein levels were significantly elevated in PFOS treated groups. TrkB protein expression increased in the 10 μM and 50 μM PFOS groups and significantly decreased in the 100 μM PFOS group. Our results demonstrated that PFOS exposure decreased miR-16 expression and increased miR-22 expression, which may represent a possible mechanism by which PFOS decreases BDNF protein levels. PFOS may inhibit BDNF-ERK-CREB signalling by increasing miR-22 levels, which may, in part, explain the mechanism of PFOS neurotoxicity.

Osteogenic sarcoma (OS) is a deadly skeletal malignancy whose cause is unknown. We report here a mouse model of OS based on conditional expression of the intracellular domain of Notch1 (NICD). Expression of the NICD in immature osteoblasts was sufficient to drive the formation of bone tumors, including OS, with complete penetrance. These tumors display features of human OS; namely, histopathology, cytogenetic complexity, and metastatic potential. We show that Notch activation combined with loss of p53 synergistically accelerates OS development in mice, although p53-driven OS is not Rbpj dependent, which demonstrates a dual dominance of the Notch oncogene and p53 mutation in the development of OS. Using this model, we also reveal the osteoblasts as the potential sources of OS., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Triangular Ag nanoprisms are a type of most-studied noble-metal nanostructures over the past decade owing to their special structural architecture and outstanding optical and catalytic properties for a wide range of applications. Nevertheless, in contrast to active research for the synthesis of phase-pure Ag nanoprisms, no asymmetric heterodimers containing Ag prisms have been developed so far, probably due to lack of suitable synthetic methods. Herein, we devise a simple ion-exchange method to synthesize Ag2S/Ag heterodimers at room temperature, through which Ag nanoprisms with controllable size and thickness can be fabricated. Formation chemistry and optical properties of the heterodimers have been investigated. These semiconductor/metal heterodimers have exhibited remarkable bactericidal activity to E. coli cells under visible light illumination.

A specific technique capable of producing high-quality RNA for rapid amplification of cDNA ends (RACE) was established for challenging tissues: leaves of the rubber tree. Total RNA was extracted by cetyltrimethylammonium bromide (CTAB)-LiCl combined with TRIzol reagent. The isolated RNA was highly intact. With RNA as template, full-length cDNA was obtained (NCBI, AY461413) by RACE.

Objective: Experimental studies have suggested green tea to be a chemopreventive agent for colorectal cancer, and many studies have examined possible associations. However, the conclusions were inconsistent or even contradictory, so we performed a meta-analysis based on published case-control studies to explore if green tea is indeed a protective factor., Methods: PubMed was searched up to May 10th, 2012 for relevant studies, and references of included studies were manually searched. Finally 13 eligible studies, involving 12,636 cases and 38,419 controls were identified. After data extraction, a meta-analysis was performed using CMA v2 software., Results: The results indicated there may be a weak but not statistically significant reduced risk of colorectal cancer with high dose of green tea intake (OR=0.95, 95% CI:0.81-1.11, p=0.490.69-0.98). This protective effect was also found in all subgroups, except in American and European populations. Sensitivity analysis indicated the result to be robust. Publication bias was not detected by either funnel plot or Egger tests., Conclusion: The results of this meta-analysis indicate a weak lower tendency for colorectal cancer development with green tea consumption, but available epidemiologic data are insufficient to conclude that green tea may protect against colorectal cancer in humans.

As a next level of nanofabrication of inorganic materials, free-standing asymmetric nanostructures with an interior space are highly desirable for new applications. In this work, we demonstrate a wet synthesis scheme for bullet-head-like nanostructures of wurtzite zinc oxide (ZnO). The synthesized asymmetric nanostructures are single crystalline, and each has an interior space. In addition to the exterior geometric anisotropy, it is found that the interior space is located at the upper part of the ZnO nanostructures; a new type of structural anisotropy has thus been revealed. On the basis of the present findings, in principle, this synthetic architecture should be applicable to other II-VI compound semiconductors through stabilizing two or more sets of crystallographic planes in solution media. The possibility of dimerization and higher ordered coupling/growth of the ZnO nanostructures has also been addressed.

We describe a synthetic investigation on the formation of carbon nanofibers using a preshaped free-standing metal-oxide catalyst (single-crystal cobalt oxide (Co(3)O(4)) nanocubes). In reacting with acetylene (C(2)H(2)) vapor, Co(3)O(4) nanocubes are reduced and reconstructed into metallic cobalt. The resultant metal catalyst with a 2-fold symmetry leads to a bilateral base growth for carbon nanofibers. Our findings indicate that an understanding of catalyst-assisted chemical vapor deposition (CVD) mechanisms can be acquired, when the shape, size, and crystal orientation of pristine metal catalysts are made known to the CVD process. By tracing their evolutional changes in structure and composition, the shape-designed model catalysts may offer new opportunities for mechanistic investigations on the chemical reactivity of nanoparticles, general catalyst-assisted material synthesis, and metal intercalation chemistry.

In this work, we report a simple "one pot" approach to prepare hollow anatase TiO 2 nanospheres via Ostwald ripening under hydrothermal conditions. Inner nanospace and highly organized crystallites in the shell structure and surface regions can be created with a wide range of controlling parameters. The formation mechanism has been investigated with TEM/ED/SEM/EDX/XRD/XPS methods. The approach shows a high versatility for structural engineering of various targeted morphological products, including inner material refills.