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This study describes an iron-catalyzed divergent oxidation of styrene into β-hydroxylmethylketone and ketone under photo-irradiation. This divergence is ascribed to the use of styrene with various substituents. More importantly, methanol is oxidized into formaldehyde in the reaction and serves as a C1 synthon. Mechanism investigations show that the reaction is initiated by oxidative SET to transfer styrene into the cation radical. The reaction pathway undergoes HAT and β-hydride elimination as well as a concerted cyclization. Particularly, several drug-like molecules, such as melperone analogue, lenperone analogue, and haloperidol analogue, are synthesized. In addition, this method is also applicable to the synthesis of natural product ( R )- atomoxetine .

Candida glabrata is believed to be the underlying cause of many human ailments, including oral, gastrointestinal, and vaginal disorders. C. glabrata-caused deep-seated infections, coupled with its resistance to antifungal drugs, may contribute to a high mortality rate. Resveratrol is a polyphenol and can achieve better therapeutic effects when administered in combination with micafungin, but the underlying molecular mechanisms remain unknown. Here, we investigate the effects of varying doses of resveratrol on the proliferation, apoptosis, and activity of macrophages, which were co-cultured with micafungin-pretreated C. glabrata. Resveratrol can restore the decreased proliferative activity of macrophages caused by the phagocytosis of C. glabrata. Further investigations demonstrated that this restoration ability exhibited a dose-dependent manner, reaching the highest level at 200 µM of resveratrol. Resveratrol tended to be more effective in inhibiting macrophage apoptosis and reducing reactive oxygen species (ROS) levels with concentration increases. In addition, at medium concentrations, resveratrol may down-regulate the expression of most inflammatory cytokines, whereas at high concentrations, it started to exert pro-inflammatory functions by up-regulating their expressions. Macrophages may shift from an anti-inflammatory (M2) phenotype to an inflammatory (M1) phenotype by resveratrol at 200 µM, and from M1 to M2 at 400 µM. Our research shows that resveratrol with micafungin are effective in treating C. glabrata infections. The resveratrol-micafungin combination can reduce the production of ROS, and promote the proliferation, inhibit the apoptosis, and activate the polarization of macrophages in a dose-dependent manner. This study offers insights into how this combination works and may provide possible direction for further clinical application of the combination., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported., (Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Schisandra sphenanthera is an extremely important medicinal plant, and its main medicinal component is bioactive lignans. The S. sphenanthera fruit is preferred by the majority of consumers, and the root, stem, and leaf are not fully used. To better understand the lignan metabolic pathway, transcriptome and metabolome analyses were performed on the four major tissues of S. sphenanthera. A total of 167,972,229 transcripts and 91,215,760 unigenes with an average length of 752 bp were identified. Tissue-specific gene analysis revealed that the root had the highest abundance of unique unigenes (9703), and the leaves had the lowest (189). Transcription factor analysis showed that MYB-, bHLH- and ERF-transcription factors, which played important roles in the regulation of secondary metabolism, showed rich expression patterns and may be involved in the regulation of processes involved in lignan metabolism. In different tissues, lignans were preferentially enriched in fruit and roots by gene expression profiles related to lignan metabolism and relative lignan compound content. Furthermore, schisandrin B is an important compound in S. sphenanthera. According to weighted gene co-expression network analysis, PAL1, C4H-2, CAD1, CYB8, OMT27, OMT57, MYB18, bHLH3, and bHLH5 can be related to the accumulation of lignans in S. sphenanthera fruit, CCR5, SDH4, CYP8, CYP20, and ERF7 can be related to the accumulation of lignans in S. sphenanthera roots. In this study, transcriptome sequencing and targeted metabolic analysis of lignans will lay a foundation for the further study of their biosynthetic genes., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Polaron formation is ubiquitous in polarized materials, but severely hampers carrier transport for which effective controlling methods are urgently needed. Here, we show that laser-controlled coherent phonon excitation enables orders of magnitude enhancement of carrier mobility via accelerating polaron transport in a prototypical material, lithium peroxide (Li 2 O 2 ). The selective excitation of specific phonon modes, whose vibrational pattern directly overlap with the polaronic lattice deformation, can remarkably reduce the energy barrier for polaron hopping. The strong nonadiabatic couplings between the electronic and ionic subsystem play a key role in triggering the migration of polaron, via promoting phonon-phonon scattering in q space within sub-picoseconds. These results extend our understanding of polaron transport dynamics to the nonequilibrium regime and allow for optoelectronic devices with ultrahigh on-off ratio and ultrafast responsibility, competitive with those of state-of-the-art devices fabricated based on free electron transport.

Veratrum (Melanthiaceae; Liliales) is a genus of perennial herbs known for the production of unique bioactive steroidal alkaloids. However, the biosynthesis of these compounds is incompletely understood because many of the downstream enzymatic steps have yet to be resolved. RNA-Seq is a powerful method that can be used to identify candidate genes involved in metabolic pathways by comparing the transcriptomes of metabolically active tissues to controls lacking the pathway of interest. The root and leaf transcriptomes of wild Veratrum maackii and Veratrum nigrum plants were sequenced and 437,820 clean reads were assembled into 203,912 unigenes, 47.67% of which were annotated. We identified 235 differentially expressed unigenes potentially involved in the synthesis of steroidal alkaloids. Twenty unigenes, including new candidate cytochrome P450 monooxygenases and transcription factors, were selected for validation by quantitative real-time PCR. Most candidate genes were expressed at higher levels in roots than leaves but showed a consistent profile across both species. Among the 20 unigenes putatively involved in the synthesis of steroidal alkaloids, 14 were already known. We identified three new CYP450 candidates (CYP76A2, CYP76B6 and CYP76AH1) and three new transcription factor candidates (ERF1A, bHLH13 and bHLH66). We propose that ERF1A, CYP90G1-1 and CYP76AH1 are specifically involved in the key steps of steroidal alkaloid biosynthesis in V. maackii roots. Our data represent the first cross-species analysis of steroidal alkaloid biosynthesis in the genus Veratrum and indicate that the metabolic properties of V. maackii and V. nigrum are broadly conserved despite their distinct alkaloid profiles., (© 2023. The Author(s).)

Aim: Neutrophil-to-lymphocyte ratio (NLR) is an index of systemic inflammation. This study is to clarify the role of NLR in body functional status, nutritional risk and nutritional status in the course of tumor., Methods: A multi-center cross-sectional study of patients with various types of malignant tumors was accrued from the whole country. There were 21,457 patients with completed clinical data, biochemical indicators, physical examination, the Patient-Generated Subjective Global Assessment (PG-SGA) and Nutrition Risk Screening 2002 (NRS2002) survey. Logistic regression analysis was used to figure out the influencing factors of NLR, and four models were established to evaluate the influence of NLR on body functions, nutritional risks and nutritional status., Results: Male patients, TNM stage IV, total bilirubin, hypertension and coronary atherosclerotic heart disease (CAHD) were independent predictors of NLR >2.5. BMI, digestive systemic tumors and triglyceride negatively affect NLR in multivariable logistic regression. NLR was an independent predictor of Karnofsky Performance Scale (KPS), fat store deficit in all degrees, moderate and severe muscle deficit, mild fluid retention and PG-SGA grade., Conclusion: Male patients and those with hypertension and CAHD are prone to systemic inflammation. Systemic inflammation significantly degrades body function status and nutritional status, increases nutritional risk and influences fat and muscle metabolism in patients with malignant tumor. Improving the intervenable indicators such as elevating albumin and pre-albumin, decreasing total bilirubin and enhancing nutrition support are imperative. Obesity and triglyceride behave like anti-systemic inflammation, which is misleading due to reverse causation in the course of malignancy., 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., (© 2023 Kang et al.)

To improve the biosafety of the nanodelivery system, this study developed novel monodisperse spherical aluminum nanoparticles (Al NPs) and evaluated their cytotoxicity in vitro and distribution and biotoxicity in vivo . Compared with gold nanoparticles of the same size, Al NPs not only had low cytotoxicity in vitro but also did not cause accumulation in major organs in vivo after intravenous injections. No significant abnormalities were observed in the serum biochemical indices of mice injected with Al NPs. Additionally, no substantial changes occurred in the histopathology of major organs, and no apparent biological toxicity was measured after consecutive injections of Al NPs. These results indicate that Al NPs have a good biological safety and provide a new method for developing low-toxicity nanomedicine., Competing Interests: The authors have no conflicts to disclose., (© 2023 Author(s).)

Background: Zika virus (ZIKV) is an emerging arbovirus of the genus flavivirus that is associated with congenital Zika syndrome (CZS) in newborns. A wide range of clinical symptoms including intellectual disability, speech delay, coordination or movement problems, and hearing and vision loss, have been well documented in children with CZS. However, whether ZIKV can invade the olfactory system and lead to post-viral olfactory dysfunction (PVOD) remains unknown., Methods: We investigated the susceptibility and biological responses of the olfactory system to ZIKV infection using mouse models and human olfactory organoids derived from patient olfactory mucosa., Findings: We demonstrate that neonatal mice infected with ZIKV suffer from transient olfactory dysfunction when they reach to puberty. Moreover, ZIKV mainly targets olfactory ensheathing cells (OECs) and exhibits broad cellular tropism colocalizing with small populations of mature/immature olfactory sensory neurons (mOSNs/iOSNs), sustentacular cells and horizontal basal cells in the olfactory mucosa (OM) of immunodeficient AG6 mice. ZIKV infection induces strong antiviral immune responses in both the olfactory mucosa and olfactory bulb tissues, resulting in the upregulation of proinflammatory cytokines/chemokines and genes related to the antiviral response. Histopathology and transcriptomic analysis showed typical tissue damage in the olfactory system. Finally, by using an air-liquid culture system, we showed that ZIKV mainly targets sustentacular cells and OECs and support robust ZIKV replication., Interpretation: Our results demonstrate that olfactory system represents as significant target for ZIKV infection, and that PVOD may be neglected in CZS patients., Funding: Stated in the acknowledgment., Competing Interests: Declaration of interests The authors declare that they have no conflict of interests., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Neovascularization is an important factor causing radiotherapy resistance, tumor growth, and metastasis. It may provides a new direction for treatment of cervical cancer., Objective and Methods: The main objective is to systematically evaluate the clinical efficacy and safety of antiangiogenic therapy combined with CCRT in the treatment of cervical cancer. We searched major Chinese and English databases to collect relevant studies from the database establishment up to April 2022. The experimental group of the studies included used CCRT combined with anti-angiogenic therapy, while another used only CCRT. We used the ' Cochrane Collaboration's tool' to assess risk of bias and RevMan 5.4 to conduct analysis., Results: Twelve studies with 793 patients were included. Use clinical efficiency and adverse reactions as effect indicators. It showed that the combination can improve the ORR (OR = 3.52, P < 0.00001), CR(OR = 2.46, P < 0.00001), DCR (OR = 2.64, P = 0.005), and OS(HR = 0.56, P = 0.03). But it increases the risk of neutropenia (OR = 1.86, P = 0.004) and hypertension (OR = 5.57, P = 0.003)., Conclusions: Combined therapy can improve the clinical efficacy of cervical cancer, but the safety needs to be considered.

With the development of the social economy over the last 30 years, non-alcoholic fatty liver disease (NAFLD) is affected by unhealthy living habits and eating styles and has gradually become an increasingly serious public health problem. It is very important to investigate the pathogenesis and treatment of NAFLD for the development of human health. Probucol is an antioxidant with a bis-phenol structure. Although probucol is a clinically used cholesterol-lowering and antiatherosclerosis drug, its mechanism has not been elucidated in detail. This paper reviews the chemical structure, pharmacokinetics and pharmacological research of probucol. Meanwhile, this paper reviews the mechanism of probucol in NAFLD. We also analyzed and summarized the experimental models and clinical trials of probucol in NAFLD. Although current therapeutic strategies for NAFLD are not effective, we hope that through further research on probucol, we will be able to find suitable treatments to solve this problem in the future., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Roasting is an important operation to produce attractive colors and distinctive flavors during the production of sesame oil. To investigate the contributions of macromolecules to the color and flavor during roasting sesame seeds, water-soluble polysaccharides (WSP) and chelator-soluble polysaccharides (CSP) sequentially extracted from sesame hull were mixed with sesame protein isolate (SPI) at different ratios (1:1, 1:2, and 2:1, w/w), then the mixtures were roasted at 180 °C for 35 min. Results showed that WSP, CSP, and SPI degraded approximately at 150 °C and SPI had the highest thermal stability. According to monosaccharide/amino acid analysis, glucose and galacturonic acid showed the highest reduction rates, as well as lysine and arginine. CSP + SPI mixtures showed greater reactivity than WSP + SPI mixtures, resulting in a darker color and many more Maillard reaction products. The predominant volatiles of roasted WSP/CSP + SPI mixtures were aldehydes and heterocyclic compounds identified by headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME/GC-MS). This work provides some new information about flavor and color development during roasting sesame seeds., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Zika virus (ZIKV) is primarily transmitted through mosquito bites and sexual contact, and vertical transmission of ZIKV has also been observed in humans. In addition, ZIKV infection via unknown transmission routes has been frequently reported in clinical settings. However, whether ZIKV can be transmitted via aerosol routes remains unknown. In this study, we demonstrated that aerosolized ZIKV is fully infectious in vitro and in vivo. Remarkably, intratracheal (i.t.) inoculation with aerosolized ZIKV led to rapid viremia and viral secretion in saliva, as well as robust humoral and innate immune responses in guinea pigs. Transcriptome analysis further revealed that the expression of genes related to viral processes, biological regulation and the immune response was significantly changed. Together, our results confirm that aerosolized ZIKV can result in systemic infection and induce both innate and adaptive immune responses in guinea pigs, highlighting the possibility of ZIKV transmission via aerosols.

Methods to probe and understand the dynamic response of materials following impulsive excitation are important for many fields, from materials and energy sciences to chemical and neuroscience. To design more efficient nano, energy, and quantum devices, new methods are needed to uncover the dominant excitations and reaction pathways. In this work, we implement a newly-developed superlet transform-a super-resolution time-frequency analytical method-to analyze and extract phonon dynamics in a laser-excited two-dimensional (2D) quantum material. This quasi-2D system, 1T-TaSe 2 , supports both equilibrium and metastable light-induced charge density wave (CDW) phases mediated by strongly coupled phonons. We compare the effectiveness of the superlet transform to standard time-frequency techniques. We find that the superlet transform is superior in both time and frequency resolution, and use it to observe and validate novel physics. In particular, we show fluence-dependent changes in the coupled dynamics of three phonon modes that are similar in frequency, including the CDW amplitude mode, that clearly demonstrate a change in the dominant charge-phonon couplings. More interestingly, the frequencies of the three phonon modes, including the strongly-coupled CDW amplitude mode, remain time- and fluence-independent, which is unusual compared to previously investigated materials. Our study opens a new avenue for capturing the coherent evolution and couplings of strongly-coupled materials and quantum systems., (© 2022. The Author(s).)

Background: Safety concerns, caused by complex and unpredictable adulterants, run through the entire industrial chain of traditional Chinese medicines (TCMs). However, the conventional circulation traceability system only focuses on a certain end or link at the back end of the TCM industrial chain, ignoring the integrity of the links cross the entire industrial chain and lacking traceability. In consequence, a strict and rational supervision system is urgently required for the entire industrial chain., Hypothesis/purpose: We hypothesize that DNA barcoding would be a suitable measure for the traceability of adulterants in the entire TCM industrial chain., Methods: In this study, Rhei Radix et Rhizoma was selected as a model to establish a traceability system for the entire TCM industrial chain. A total of 110 samples, including leaves, seeds, roots, decoction pieces, and traditional Chinese patent medicines (TCPMs), were collected upstream, midstream, and downstream of the entire industrial chain of Rhei Radix et Rhizoma. The ndhF-rpl32 fragment rather than the universal DNA barcodes, which could not distinguish the three original species of Rhei Radix et Rhizoma, was selected as a specific DNA barcode to evaluate the practical application of DNA barcoding in the chain., Results: The results showed that the ndhF-rpl32 fragment in all samples could be amplified and bi-directionally sequenced. Based on the standard operating procedures of DNA barcoding, the ndhF-rpl32 fragment clearly distinguished the seven Rheum species collected upstream of the entire industrial chain. For the samples collected midstream and downstream of the entire industrial chain, 25% of the 36 commercial decoction pieces samples were identified as adulterants, whereas the eight TCPM samples were all derived from genuine Rhei Radix et Rhizoma., Conclusions: This study shows that DNA barcoding is a powerful and suitable technology that can be applied to trace TCMs in the entire industrial chain, thereby assuring clinical medication safety., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Background: Traumatic haemarthrosis was hypothesized to be the etiology of temporomandibular (TMJ) ankylosis. Here, taking haematoma absorbance as a control, we aimed to reveal the molecular mechanisms involved in haematoma organizing into ankylosis using transcriptome microarray profiles., Material/methods: Disk removal was performed to building haematoma absorbance (HA) in one side of TMJ, while removal of disk and articular fibrous layers was performed to induced TMJ ankylosis through haematoma organization (HO) in the contralateral side in a sheep model. Haematoma tissues harvested at days 1, 4 and 7 postoperatively were examined by histology, and analyzed by Affymetrix OviGene-1&#95;0-ST microarrays. The DAVID were recruited to perform the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis for the different expression genes (DEGs). The DEGs were also typed into protein-protein interaction (PPI) networks to get the interaction data. Six significant genes screened from PPI analysis, were confirmed by real-time PCR., Results: We found 268, 223 and 17 DEGs at least twofold at days 1, 4 and 7, respectively. At day 1, genes promoting collagen ossification (POSTN, BGN, LUM, SPARC), cell proliferation (TGF-β), and osteogenic differentiation of mesenchymal stem cells (BMP-2) were up-regulated in the HO side. At day 4, several genes involved in angiogenesis (KDR, FIT1, TEK) shower higher expression in the HO side. While HA was characterized by a continuous immune and inflammatory reaction., Conclusions: Our results provide a comprehensive understanding of the role of haematoma in the onset and progress of TMJ ankylosis. The study will contribute to explaining why few injured TMJs ankylose and most do not from the molecular level., (© 2021. The Author(s).)

Protein S-nitrosylation is one of the most important post-translational modifications, a well-grounded understanding of S-nitrosylation is very significant since it plays a key role in a variety of biological processes. For an uncharacterized protein sequence, it is a very meaningful problem for both basic research and drug development when we can firstly identify whether it is a S-nitrosylation protein or not, and then predict the specific S-nitrosylation site(s). This work has proposed two models for identifying S-nitrosylation protein and its PTM sites. Firstly, three kinds of features are extracted from protein sequence: KNN scoring of functional domain annotation, PseAAC and bag-of-words based on the physical and chemical properties of amino acids. Secondly, the synthetic minority oversampling technique is used to balance the data sets, and some state-of-the-art classifiers and feature fusion strategies are performed on the balanced data sets. In the five-fold cross-validation for predicting S-nitrosylation proteins, the results of Accuracy (ACC), Matthew's correlation coefficient (MCC) and area under ROC curve (AUC) are 81.84%, 0.5178, 0.8635, respectively. Finally, a model for predicting S-nitrosylation sites has been constructed on the basis of tripeptide composition (TPC) and the composition of k-spaced amino acid pairs (CKSAAP). To eliminate redundant information and improve work efficiency, elastic nets are employed for feature selection. The five-fold cross-validation tests have indicated the promising success rates of the proposed model. For the convenience of related researchers, the web-server named "RF-SNOPS" has been established at http://www.jci-bioinfo.cn/RF-SNOPS.

Optical control of structural and electronic properties of Weyl semimetals allows development of switchable and dissipationless topological devices at the ultrafast scale. An unexpected orbital-selective photoexcitation in type-II Weyl material WTe 2 is reported under linearly polarized light (LPL), inducing striking transitions among several topologically-distinct phases mediated by effective electron-phonon couplings. The symmetry features of atomic orbitals comprising the Weyl bands result in asymmetric electronic transitions near the Weyl points, and in turn a switchable interlayer shear motion with respect to linear light polarization, when a near-infrared laser pulse is applied. Consequently, not only annihilation of Weyl quasiparticle pairs, but also increasing separation of Weyl points can be achieved, complementing existing experimental observations. In this work, we provide a new perspective on manipulating the Weyl node singularity and coherent control of electron and lattice quantum dynamics simultaneously.

Objective: To study the role and mechanism of histone deacetylase 1 (HDAC1) and histone deacetylase 2 (HDAC2) in mouse neuronal development., Methods: The mice with Synapsin1-Cre recombinase were bred with HDAC1&2 flox/flox mice to obtain the mice with neuron-specific HDAC1&2 conditional knockout (knockout group), and their littermates without HDAC1&2 knockout were used as the control group. The general status of the mice was observed and survival curves were plotted. Brain tissue samples were collected from the knockout group and the control group. Western blot and immunohistochemistry were used to measure the protein expression of related neuronal and axonal markers, neuronal nuclear antigen (NeuN), non-phosphorylated neurofilament heavy chain (np-NF200), and phosphorylated neurofilament heavy chain (p-NF200), as well as the downstream effector of the mTOR signaling pathway, phosphorylated S6 ribosomal protein (p-S6)., Results: The mice with HDAC1&2 conditional knockout usually died within one month after birth and were significantly smaller than those in the control group, with motor function abnormalities such as tremor and clasping of hindlimbs. Compared with the control group, the knockout group had significant reductions in the protein expression levels of NeuN, np-NF200, p-NF200, and p-S6 ( P < 0.05; n =3)., Conclusions: Deletion of HDAC1 and HDAC2 in mouse neurons results in reduced neuronal maturation and axonal dysplasia, which may be associated with the mTOR signaling pathway.

The origin of charge density waves (CDWs) in TiSe[Formula: see text] has long been debated, mainly due to the difficulties in identifying the timescales of the excitonic pairing and electron-phonon coupling (EPC). Without a time-resolved and microscopic mechanism, one has to assume simultaneous appearance of CDW and periodic lattice distortions (PLD). Here, we accomplish a complete separation of ultrafast exciton and PLD dynamics and unravel their interplay in our real-time time-dependent density functional theory simulations. We find that laser pulses knock off the exciton order and induce a homogeneous bonding-antibonding transition in the initial 20 fs, then the weakened electronic order triggers ionic movements antiparallel to the original PLD. The EPC comes into play after the initial 20 fs, and the two processes mutually amplify each other leading to a complete inversion of CDW ordering. The self-amplified dynamics reproduces the evolution of band structures in agreement with photoemission experiments. Hence we resolve the key processes in the initial dynamics of CDWs that help elucidate the underlying mechanism.

Purpose: Orthokeratology (OK) lens is a popular optical method to control myopia progression. This study aimed to assess the effect of OK lens on axial length change compared with glasses., Methods: PubMed, Web of Science, and Embase were searched to retrieve the related articles. Then, the articles were selected according to predefined criteria. Standardized mean difference (SMD) and 95% confidence interval (CI) were selected as effect size for combining and analyzing the change in axial length., Results: A total of 13 articles were included in the present study. Different models were selected according to the heterogeneity of each analysis. The axial length change in OKs group was significantly smaller than control group; SMD (95% CI) of change in axial length was - 0.857 (- 1.146, - 0.568), p < 0.001 at the end of 1 year and - 0.701 (- 1.675, 0.272), p < 0.001 at the end of 2 years or longer time., Conclusions: OK lens treatment appears more effective in slowing axial elongation than glasses during the early treatment of myopia in children.

Several previous genomic studies have focused on adaptation to high elevations, but these investigations have been largely limited to endotherms. Snakes of the genus Thermophis are endemic to the Tibetan plateau and therefore present an opportunity to study high-elevation adaptations in ectotherms. Here, we report the de novo assembly of the genome of a Tibetan hot-spring snake ( Thermophis baileyi ) and then compare its genome to the genomes of the other two species of Thermophis , as well as to the genomes of two related species of snakes that occur at lower elevations. We identify 308 putative genes that appear to be under positive selection in Thermophis We also identified genes with shared amino acid replacements in the high-elevation hot-spring snakes compared with snakes and lizards that live at low elevations, including the genes for proteins involved in DNA damage repair ( FEN1 ) and response to hypoxia ( EPAS1 ). Functional assays of the FEN1 alleles reveal that the Thermophis allele is more stable under UV radiation than is the ancestral allele found in low-elevation lizards and snakes. Functional assays of EPAS1 alleles suggest that the Thermophis protein has lower transactivation activity than the low-elevation forms. Our analysis identifies some convergent genetic mechanisms in high-elevation adaptation between endotherms (based on studies of mammals) and ectotherms (based on our studies of Thermophis )., Competing Interests: The authors declare no conflict of interest.

Background: pN stage and breast cancer subtypes (BCS) are both well-recognized prognostic indicators. Our previous work has highlighted that patients even with the same pN stage exhibited a significant survival difference in different BCS. Given this achievement, we hypothesized that a statistical interaction might exist between pN stage and BCS. The aim of this retrospective cohort study was to compare the prognostic value of the combined pN stage and BCS (pN new stage) with either pN stage or BCS alone, and to determine if this combined new stage could serve as an alternative discriminator of outcome., Methods: We combined pN stage and BCS to create a new variable named pN new stage and then divided it into four groups: pN0 new , pN1 new , pN2 new , and pN3 new . Survival analysis was performed with the use of the Kaplan-Meier method and the log-rank test was used for univariate analysis. For multivariate analysis, cox proportional hazard models were applied, allowing for the estimation of disease-free survival (DFS). To assess discriminatory accuracy of the models, we compared the area under the receiver-operating characteristic curve (AUROC), the Akaike information criterion (AIC), and the Bayesian information criterion (BIC) values. Then, we used this pN new stage to generate a TN new M staging system according to the 7th AJCC staging system., Results: A statistical interaction between pN stage and BCS was found. In multivariate survival analysis, the pN new stage has been confirmed as an independent prognostic variable of 5-year DFS. The pN new stage, with a smaller AIC or BIC value and larger AUROC, was a more powerful predictor of DFS than either pN stage or BCS alone. Results were validated in a separate cohort of patients. The TN new M stage proposed in our present study was found comparable to the new 8th AJCC edition which includes anatomic T, N, and M plus tumor grade and the status of the biomarkers Her-2, ER, and PR with respect to prognostic value for breast cancer patients., Conclusions: The pN new stage (combined pN stage and BCS) appears to be a more powerful predictor and discriminator for the outcome of breast cancer, as compared to pN stage or BCS alone, and the TN new M stage may serve as a simple, easy-to-use alternative to the 8th AJCC edition staging manual.

Objective: To analyze the characteristics of lymph node metastasis and prognosis in patients with T1 breast cancer., Methods: The clinicopathological data of 354 patients with T1 breast cancer after standard treatment from March 2007 to September 2011 were collected to analyze the relationship between the clinical characteristics of T1 breast cancer, lymph node metastasis and prognostic features., Results: In the 354 patients with T1 breast cancer, 105 patients (29.7%) had lymph node metastasis, among them 73 cases (69.5%) had 1-3 lymph node metastasis, and 32 cases (30.5%) had more than 4 lymph node metastasis. The lymph node metastasis rate was 8.3% in T1a patients, 39.7% in T1b patients, and 30.4% in T1c cases (P = 0.005). Pairwise comparison showed that the difference of lymph node metastasis rate between T1a, T1b and T1c patients was statistically significant (P = 0.001 and P = 0.006, respectively). The difference of lymph node metastasis rates in T1b and T1c patients was statistically insignificant (P = 0.171). In the 354 patients of T1 breast cancer, 92 patients had vascular tumor thrombi and their lymph node metastasis rate was 71.7%, while the lymph node metastasis rate in 262 patients without vascular tumor thrombus was 14.9% (P < 0.001). The median follow-up was 49 months (range 27-81 months). 12 patients developed recurrence, and 3 patients died, one of them died of cerebrovascular accident. The 4-year disease-free survival for all patients was 96.6%, and the 4-year overall survival rate was 99.2%., Conclusions: There is a correlation between vascular tumor thrombus, tumor size and lymph node metastasis rate. The lymph node metastasis rate is lower in T1a patients and relatively higher in T1b/c patients. Compared with patients without vascular tumor thrombus, the T1 breast cancer patients with vascular tumor thrombi have a higher lymph node metastasis rate. Generally speaking, there is a still good prognosis in patients with T1 breast cancer.

Remote sensing has been extensively applied in agriculture for its objectiveness and promptness. However, few applications are available for monitoring natural medicinal plants. In the paper, a multilevel monitoring system, which includes satellite and aerial remote sensing, as well as ground investigation, was initially proposed to monitor natural Rheum tanguticum resource in Baihe Pasture, Zoige County, Sichuan Province. The amount of R. tanguticum from images is M = S*ρ and S is vegetation coverage obtained by satellite imaging, whereas ρ is R. tanguticum density obtained by low-altitude imaging. Only the R. tanguticum which coverages exceeded 1 m(2) could be recognized from the remote sensing image because of the 0.1 m resolution of the remote sensing image (called effective resource at that moment), and the results of ground investigation represented the amounts of R. tanguticum resource in all sizes (called the future resource). The data in paper showed that the present available amount of R. tanguticum accounted for 4% to 5% of the total quantity. The quantity information and the population structure of R. tanguticum in the Baihe Pasture were initially confirmed by this system. It is feasible to monitor the quantitative distribution for natural medicinal plants with scattered distribution.

A superparamagnetic reduced graphene oxide-Fe(3)O(4) hybrid composite (rGO-Fe(3)O(4)) was prepared via a facile and straightforward method through the solvothermal reaction of iron (III) acetylacetonate (Fe(acac)(3)) and graphene oxide (GO) in ethylenediamine (EDA) and water. By this method, chemical reduction of GO as well as the formation of Fe(3)O(4) nanoparticles (NPs) can be achieved in one step. The Fe(3)O(4) NPs are firmly deposited on the surfaces of rGO, avoiding their reassembly to graphite. The rGO sheets prevent the agglomeration of Fe(3)O(4) NPs and enable a uniform dispersion of these metal oxide particles. The size distribution and coverage density of Fe(3)O(4) NPs deposited on rGO can be controlled by varying the initial mass ratio of GO and iron precursor, Fe(acac)(3). With an initial mass ratio of GO and Fe(acac)(3) of 5:5, the surfaces of rGO sheets are densely covered by spherical Fe(3)O(4) NPs with an average size of 19.9 nm. The magnetic-functionalized rGO hybrid exhibits a good magnetic property and the specific saturation magnetization (M(s)) is 13.2 emu g(-1). The adsorption test of methylene blue from aqueous solution demonstrates the potential application of this rGO-Fe(3)O(4) hybrid composite in removing organic dyes from polluted water.

Objective: To investigate the PSA level of 16 222 asymptematic men in Shenzhen who came from different areas of China, in order to find out the PSA levels of Chinese men., Methods: Serum samples of 16 222 men who came to Peking University Shenzhen Hospital for health examination were collected, all of whom had no symptoms. Their serum PSA levels were measured with MEIA with ILMA instrument., Results: The mean PSA level of the 16 222 men in our research was 0.986 μg/L, and the standard deviation was 1.190. The 95% percentile was 2.375 μg/L. Of all the cases ,the 95% percentile of 15 498 was lower than 2.5 μg/L, about 95.472%;that of 699 was between 2.5-10.0 μg/L, about 4.306%;And if took 4.0 μg/L as reference value,that of 15 948 cases was below 4.0 μg/L, about 98.244%;that of 249 was between 4.0-10.0 μg/L, about 1.534%;That of only 36 cases was greater than 10.0 μg/L, about 0.222%;The 95% percentiles of the different age groups were: 10-19 years 0-1.067 μg/L;20-29 years 0-1.818 μg/L;30-39 years 0-1.914 μg/L;40-49 years 0-2.001 μg/L;50-59 years 0-2.900 μg/L;60-69 years 0-5.862 μg/L;70-79 years 0-8.536 μg/L;elder than 80 years 0-12.869 μg/L;There were statistic differences between thedifferent age groups., Conclusion: Our data demonstrate that the mean value of PSA levels of Chinese men is 0.986 μg/L at present stage, and the 95% percentile is 2.375 g/L. Our PSA levels of each age group are different from Oesterling's reference values which are commonly accepted in the world. The PSA level of Chinese men who are under 60 years is lower than that of Euramericans, while the PSA level of Chinese men who are above 60 years is higher than that of Euramericans. This shows that for the men who are under 60 the reference value should be 2.5 μg/L, while for the men who are above 60, we could still use 4 μg/L as reference value.

Introduction: Laparoscopic renal cyst decortication has become the standard of care for management of large symptomatic simple renal cysts. The aim of the present case report is to present such a case in an ambulatory setting., Case Report: A 41-year-old woman presented with a 3 year history of a painful 9 cm x 7.3 cm right lower pole simple renal cyst. Laparoscopic renal cyst decortication was performed through three 5 mm trocars. The operating time was 145 minutes. There were no intraoperative or postoperative complications. The wounds were infiltrated with a total of 20 cc of 0.25% Marcaine. At the end of the procedure, she also received 1.3 g of acetaminophen rectally and 30 mg of ketorolac intravenously. The patient remained in the recovery room for a total of 3 hours. She was hemodynamically stable and was able to ambulate right away. She was discharged home directly from the recovery room and remained pain free on subsequent follow ups at 3 days and 1 month., Comments: The present case report is a new trend in the laparoscopic management of renal cysts whereby patients can be treated in an ambulatory setting. This would make laparoscopic management even more advantageous when compared to percutaneous drainage and sclerotherapy. In an era of increasing health care costs, performing such cases in an ambulatory setting provides cost effective management in patients who are compliant.

Vaso-cutaneous fistulae occur rarely after vasectomy. We report three cases encountered in our hospital over the last 18 years and recommend technical considerations to avoid this complication.