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An analytical method was developed for the screening of 172 veterinary drugs in traditional Chinese medicine Galli Gigerii Endothelium Corneum by high-performance liquid chromatography tandem mass spectrometry. The samples were pretreated by a modified QuEChERS method. A Zorbax Eclipse plus C18 column (1.8 μm, 3.0 × 150 mm2, Agilent) was used for the separation of analytes by gradient elution. All analytes were detected by electrospray ionization mass spectrometry with multiple reaction monitoring mode. Good linearity with R  ≥ 0.99 was exhibited for all analytes within the respective range. The recoveries of all monitored analytes ranged from 55.4 to 127.6% at three spiked levels (limit of quantitation—LOQ, 2-fold LOQ, 10-fold LOQ), with relative standard deviations <17.8%. The estimated LOQ levels were 0.2–20 μg/kg. The application of this method provides a reference for the safety control of traditional Chinese medicines. [ABSTRACT FROM AUTHOR]

Aims The aim of this study was to reconstruct the evolutionary framework of the genus Umbelopsis by using modern taxonomic strategies and evaluating the quality of oil and prospective uses of three distinct species. Methods and results Three species of Umbelopsis were identified based on morphological characteristics and phylogenetic evidence obtained from three genes (ITS, LSU, and ACT). A new species of Umbelopsis was described and illustrated, and subsequently named U. ophiocordycipiticola. The characteristics of U. ophiocordycipiticola exhibited sporangia with a diameter ranging from 8 to 17 µm. and sporangiospores that were oval to ellipsoidal in shape, irregularly angular, with dimensions of ∼1.9–2.9 × 1.7–3.0 µm. Gas chromatography and mass spectrometry (GC–MS) were used to examine the composition of fatty acids. Notably, U. ophiocordycipiticola showed a significantly higher oil content of 50.89% in dry cell weight (DCW) compared to U. vinacea and U. ramanniana. The mean proportion of polyunsaturated fatty acids (PUFAs) in U. ophiocordycipiticola was 32.38%, and the maximum levels of γ-linolenic acid (GLA), arachidonic acid (ARA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) in U. ophiocordycipiticola were found to be 14.51, 0.24, 0.54, and 0.53%, respectively. The biodiesel quality from all three species complied with applicable standards set by the American Association for Testing and Materials (ASTM 6751) and the Brazilian National Petroleum Agency (ANP 255). Conclusions The establishment of a novel species, U. ophiocordycipiticola , was strongly supported by morphological and molecular evidence. Umbelopsis ophiocordycipiticola exhibited a high-value PUFA content. Additionally, three Umbelopsis species demonstrated good quality for biodiesel production. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Is dietary non-enzymatic antioxidant capacity related to semen quality? SUMMARY ANSWER The only statistically significant association of semen quality parameters with dietary total antioxidant capacity (DTAC) detected was an inverse association between DTAC and ejaculate volume. WHAT IS KNOWN ALREADY Growing interest exists regarding the role of diet in influencing semen quality. While DTAC is linked to favorable health outcomes, its association with semen quality, especially among men attending infertility clinics, remains understudied. STUDY DESIGN, SIZE, DURATION This cross-sectional study was carried out between June and December of 2020. In total, 1715 participants were included in the final analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS Men who attended an infertility clinic in China were enrolled. Experienced clinical technicians performed the semen analysis. The DTAC indices included the ferric-reducing ability of plasma, oxygen radical absorbance capacity, total reactive antioxidant potential, and Trolox equivalent antioxidant capacity. The quantile regression model was used for multivariate analysis. MAIN RESULTS AND THE ROLE OF CHANCE After adjustment for a variety of confounding variables, a significant inverse association was identified between DTAC and ejaculate volume (βcontinuous FRAP = −0.015, 95% CI = −0.023, −0.006, βT3 vs T1 = −0.193, 95% CI = −0.379, −0.006, P trend = 0.007; βcontinuous TRAP = −0.019, 95% CI = −0.041, 0.002, βT3 vs T1 = −0.291, 95% CI = −0.469, −0.112, P trend = 0.002). The majority of DTAC indices have no statistically significant association with semen quality parameters. LIMITATIONS, REASONS FOR CAUTION We cannot infer causality because of the nature of the cross-sectional study design. The robustness of the conclusion may be compromised by the exactness of non-enzymatic antioxidant capacity estimation. WIDER IMPLICATIONS OF THE FINDINGS Our findings demonstrated no association between DTAC indices and semen quality parameters among men attending an infertility clinic, except for ejaculate volume. Even though our findings are mostly non-significant, they contribute novel knowledge to the field of study while also laying the groundwork for future well-designed studies. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the JieBangGuaShuai Project of Liaoning Province [grant number 2021JH1/10400050], the Clinical Research Cultivation Project of Shengjing Hospital [grant number M1590], and the Outstanding Scientific Fund of Shengjing Hospital [grant number M1150]. The sponsors had no role in study design, or in the collection, analysis, and interpretation of data, or in the writing of the report, or in the decision to submit the article for publication. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Objective Evictions are important social and behavioral determinants of health. Evictions are associated with a cascade of negative events that can lead to unemployment, housing insecurity/homelessness, long-term poverty, and mental health problems. In this study, we developed a natural language processing system to automatically detect eviction status from electronic health record (EHR) notes. Materials and Methods We first defined eviction status (eviction presence and eviction period) and then annotated eviction status in 5000 EHR notes from the Veterans Health Administration (VHA). We developed a novel model, KIRESH, that has shown to substantially outperform other state-of-the-art models such as fine-tuning pretrained language models like BioBERT and Bio_ClinicalBERT. Moreover, we designed a novel prompt to further improve the model performance by using the intrinsic connection between the 2 subtasks of eviction presence and period prediction. Finally, we used the Temperature Scaling-based Calibration on our KIRESH-Prompt method to avoid overconfidence issues arising from the imbalance dataset. Results KIRESH-Prompt substantially outperformed strong baseline models including fine-tuning the Bio_ClinicalBERT model to achieve 0.74672 MCC, 0.71153 Macro-F1, and 0.83396 Micro-F1 in predicting eviction period and 0.66827 MCC, 0.62734 Macro-F1, and 0.7863 Micro-F1 in predicting eviction presence. We also conducted additional experiments on a benchmark social determinants of health (SBDH) dataset to demonstrate the generalizability of our methods. Conclusion and Future Work KIRESH-Prompt has substantially improved eviction status classification. We plan to deploy KIRESH-Prompt to the VHA EHRs as an eviction surveillance system to help address the US Veterans' housing insecurity. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Are dietary fat and fatty acid (FA) intakes related to the odds of asthenozoospermia? SUMMARY ANSWER Plant-based fat consumption was associated with decreased asthenozoospermia odds, while the consumption of animal-based monounsaturated fatty acid (MUFA) was positively related to asthenozoospermia odds. WHAT IS KNOWN ALREADY Dietary fat and FA are significant ingredients of a daily diet, which have been demonstrated to be correlated to the reproductive health of men. However, to date, evidence on fat and FA associations with the odds of asthenozoospermia is unclear. STUDY DESIGN, SIZE, DURATION The hospital-based case–control study was performed in an infertility clinic from June 2020 to December 2020. Briefly, 549 asthenozoospermia cases and 581 controls with normozoospermia were available for final analyses. PARTICIPANTS/MATERIALS, SETTING, METHODS We collected dietary data through a verified food frequency questionnaire of 110 food items. Asthenozoospermia cases were ascertained according to the World Health Organization guidelines. To investigate the correlations of dietary fat and FA consumptions with the odds of asthenozoospermia, we calculated the odds ratios (ORs) and corresponding 95% CIs through unconditional logistic regression models. MAIN RESULTS AND THE ROLE OF CHANCE Relative to the lowest tertile of consumption, the highest tertile of plant-based fat intake was inversely correlated to the odds of asthenozoospermia (OR = 0.68, 95% CI = 0.50–0.91), with a significant dose–response relation (OR = 0.85, 95% CI = 0.75–0.97, per standard deviation increment). Inversely, animal-based MUFA intake (OR = 1.49, 95% CI = 1.04–2.14) was significantly correlated to increased odds of asthenozoospermia, and an evident dose–response relation was also detected (OR = 1.24, 95% CI = 1.05-1.45, per standard deviation increment). Subgroup analyses showed similar patterns of associations to those of the primary results. Moreover, we observed significant interactions on both multiplicative and additive scales between animal-based MUFA and cigarette smoking. LIMITATIONS, REASONS FOR CAUTION Selection bias and recall bias were unavoidable in any of the observational studies. As we failed to obtain the information of trans-fatty acid (TFA) consumption, the relation of TFA intake and asthenozoospermia odds was unclear. WIDER IMPLICATIONS OF THE FINDINGS This study indicated that different sources of fat and FAs might exert different effects on the etiology of asthenozoospermia, and cigarette smoking could exacerbate the adverse effect of high animal-based MUFA intake on asthenozoospermia. Our findings provide novel evidence pertaining to the fields of prevention of asthenozoospermia through decreasing animal-derived fat and FA consumptions and smoking cessation. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the JieBangGuaShuai Project of Liaoning Province, Natural Science Foundation of Liaoning Province, Clinical Research Cultivation Project of Shengjing Hospital, and Outstanding Scientific Fund of Shengjing Hospital. All authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Are dietary phytochemicals associated with the risk of teratozoospermia? SUMMARY ANSWER Dietary intake of carotene, including total carotene, α-carotene, β-carotene as well as retinol equivalent, and lutein + zeaxanthin, were inversely correlated with the risk of teratozoospermia. WHAT IS KNOWN ALREADY Phytochemicals are natural plant derived bioactive compounds, which have been reported to be potentially associated with male reproductive health. To date, no study has investigated the association between phytochemical intake and the risk of teratozoospermia. STUDY DESIGN, SIZE, DURATION This hospital-based case–control study, which included 146 newly diagnosed teratozoospermia cases and 581 controls with normozoospermia from infertile couples, was conducted in a hospital-based infertility clinic in China, from June 2020 to December 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS Dietary information was collected using a validated semi-quantitative 110-item food frequency questionnaire. Unconditional logistic regression was applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between phytochemical (i.e. phytosterol, carotene, flavonoid, isoflavone, anthocyanidin, lutein + zeaxanthin, and resveratrol) intake and the risk of teratozoospermia. MAIN RESULTS AND THE ROLE OF CHANCE We observed a decreased risk of teratozoospermia for the highest compared with the lowest tertile consumption of total carotene (OR = 0.40, 95% CI = 0.21–0.77), α-carotene (OR = 0.53, 95% CI = 0.30–0.93), β-carotene (OR = 0.47, 95% CI = 0.25–0.88), retinol equivalent (OR = 0.47, 95% CI = 0.24–0.90), and lutein + zeaxanthin (OR = 0.35, 95% CI = 0.19–0.66), with all of the associations showing evident linear trends (all P trend <0.05). In addition, significant dose–response associations were observed between campestanol and α-carotene consumption and the risk of teratozoospermia. Moreover, there was a significant multiplicative interaction between BMI and lutein + zeaxanthin intake (P interaction <0.05). LIMITATIONS, REASONS FOR CAUTION The cases and controls were not a random sample of the entire target population, which could lead to admission rate bias. Nevertheless, the controls were enrolled from the same infertility clinic, which could reduce the bias caused by selection and increase the comparability. Furthermore, our study only included a Chinese population, therefore caution is required regarding generalization of our findings to other populations. WIDER IMPLICATIONS OF THE FINDINGS Dietary phytochemicals, namely carotene, lutein, and zeaxanthin, might exert a positive effect on teratozoospermia. These phytochemicals are common in the daily diet and dietary supplements, and thus may provide a preventive intervention for teratozoospermia. STUDY FUNDING/COMPETING INTERESTS This study was funded by Natural Science Foundation of Liaoning Province (No. 2022-MS-219 to X.B.W.), Outstanding Scientific Fund of Shengjing Hospital (No. M1150 to Q.J.W.), Clinical Research Cultivation Project of Shengjing Hospital (No. M0071 to B.C.P.), and JieBangGuaShuai Project of Liaoning Province (No. 2021JH1/1040050 to Y.H.Z.). All authors declared that there was no conflict of interest. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Deciphering the intrinsic molecular logic of empirical crop breeding from a genomic perspective is a decisive prerequisite for breeding-by-design (BbD), but remains not well established. Here, we decoded the historical features of past rice breeding by phenotyping and haplotyping 546 accessions covering the majority of cultivars bred in the history of Northeast China (NEC). We revealed that three groups founded the genetic diversities in NEC rice with distinct evolution patterns and traced and verified the breeding footprints to known or genome-wide association study (GWAS)-detected quantitative trait loci (QTLs), or introgressions from indica sub-species with chronological changes in allele frequencies. Then we summarized a rice breeding trend/principle in NEC, and combined with the successful example in breeding and application of Zhongkefa5 to demonstrate the guiding value of our conclusion for BbD in practice. Our study provides a paradigm for decoding the breeding history of a specific crop to guide BbD, which may have implications in different crop breeding. The genomic decoding of rice breeding history in Northeast China, along with the successful example in breeding of Zhongkefa5, shows guiding value for rice breeding-by-design (BbD) and may have implications in different crop breeding. [ABSTRACT FROM AUTHOR]

Helicase-like transcription factor (HLTF) has been found to be involved in the maintenance of genome stability and tumour suppression, but whether its downregulation in cancers is associated with posttranslational regulation remains unclear. Here, we observed that HLTF was significantly downregulated in hepatocellular carcinoma (HCC) tissues and positively associated with the survival of HCC patients. Mechanistically, the decreased expression of HLTF in HCC was attributed to elevated β-TrCP-mediated ubiquitination and degradation. Knockdown of HLTF enhanced p62 transcriptional activity and mammalian target of rapamycin (mTOR) activation, leading to HCC tumourigenesis. Inhibition of mTOR effectively blocked β-TrCP overexpression- or HLTF knockdown-mediated HCC tumourigenesis and metastasis. Furthermore, in clinical tissues, decreased HLTF expression was positively correlated with elevated expression of β-TrCP, p62, or p-mTOR in HCC patients. Overall, our data not only uncover new roles of HLTF in HCC cell proliferation and metastasis, but also reveal a novel posttranslational modification of HLTF by β-TrCP, indicating that the β-TrCP/HLTF/p62/mTOR axis may be a new oncogenic driver involved in HCC development. This finding provides a potential therapeutic strategy for HCC patients by targeting the β-TrCP/HLTF/p62/mTOR axis. [ABSTRACT FROM AUTHOR]

Background SHR7390 is a novel, selective MEK1/2 inhibitor. Here, we report results from two phase I trials conducted to evaluate the tolerability, safety and antitumor activity of SHR7390 monotherapy for advanced solid tumors and SHR7390 plus camrelizumab for treatment-refractory advanced or metastatic colorectal cancer (CRC). Patients and Methods Patients received SHR7390 alone or combined with fixed-dose camrelizumab (200 mg every 2 weeks) in an accelerated titration scheme to determine the maximum tolerated dose (MTD). A recommended dose for expansion was determined based on the safety and tolerability of the dose-escalation stage. The primary endpoints were dose limiting toxicity (DLT) and MTD. Results In the SHR7390 monotherapy trial, 16 patients were enrolled. DLTs were reported in the 1.0 mg cohort, and the MTD was 0.75 mg. Grade ≥3 treatment-related adverse events (TRAEs) were recorded in 4 patients (25.0%). No patients achieved objective response. In the SHR7390 combination trial, 22 patients with CRC were enrolled. One DLT was reported in the 0.5 mg cohort and the MTD was not reached. Grade ≥3 TRAEs were observed in 8 patients (36.4%), with the most common being rash (n=4). One grade 5 TRAE (increased intracranial pressure) occurred. Five patients (22.7%) achieved partial response, including one of 3 patients with MSS/MSI-L and BRAF mutant tumors, one of 15 patients with MSS/MSI-L and BRAF wild type tumors, and all 3 patients with MSI-H tumors. Conclusions SHR7390 0.5 mg plus camrelizumab showed a manageable safety profile. Preliminary clinical activity was reported regardless of MSI and BRAF status. [ABSTRACT FROM AUTHOR]

The most common socioeconomic healthcare issues in clinical are burns, surgical incisions and other skin injuries. Skin lesion healing can be achieved with nanomedicines and other drug application techniques. This study developed a nano-spray based on cross-linked amorphous calcium peroxide (CaO2) nanoparticles of polyacrylic acid (PAA) for treating skin wounds (PAA-CaO2 nanoparticles). CaO2 serves as a 'drug' precursor, steadily and continuously releasing calcium ions (Ca2+) and hydrogen peroxide (H2O2) under mildly acidic conditions, while PAA-CaO2 nanoparticles exhibited good spray behavior in aqueous form. Tests demonstrated that PAA-CaO2 nanoparticles exhibited low cytotoxicity and allowed L929 cells proliferation and migration in vitro. The effectiveness of PAA-CaO2 nanoparticles in promoting wound healing and inhibiting bacterial growth in vivo was assessed in SD rats using full-thickness skin defect and Staphylococcus aureus (S.aureus)-infected wound models based thereon. The results revealed that PAA-CaO2 nanoparticles demonstrated significant advantages in both aspects. Notably, the infected rats' skin defects healed in 12 days. The benefits are linked to the functional role of Ca2+ coalesces with H2O2 as known antibacterial and healing-promoted agents. Therefore, we developed nanoscale PAA-CaO2 sprays to prevent bacterial development and heal skin lesions. [ABSTRACT FROM AUTHOR]

As we all know, medical postgraduate education is very important for training high-quality clinicians, and can have a long-term impact on the promotion of the global health service system. In recent years, following the example of developed countries in Europe and America, the Chinese government has reformed the training mode of medical postgraduates and implemented the double tutor system. Although this system will bring many positive effects in theory, the difficulties encountered in implementing this system are real and need the joint efforts of schools, tutors and students to solve them. This article closely follows the background of the current era, compares the differences between Chinese and foreign graduate training modes, and emphatically discusses the significance and problems of the double tutor system in the postgraduate education reform in China. [ABSTRACT FROM AUTHOR]

A line search penalty-free sequential quadratic programming method is proposed for nonlinear equality-constrained optimization. Generally, feasible directions are used to minimize the measurement of the constraint violation in order to deal with the inconsistency in the linearized constraints while optimal directions aim to improve the measure of optimality. A basic feature of the proposed method is that a line search direction that is some convex combination of a feasible direction and an optimal direction is utilized at each iteration, making either the value of the Lagrangian function or the measure of constraint violation sufficiently reduced. Global convergence of the method is analyzed without the feasibility restoration phase. Under the usual assumptions the method is shown to be superlinearly convergent locally without the second-order correction and hence the Maratos effect can be avoided. Numerical experiments on several examples illustrate the local behavior of the method. [ABSTRACT FROM AUTHOR]

Background: The impact of HER2 somatic mutations in colorectal carcinoma (CRC) has not been well studied and its relationship with microsatellite instability‐high (MSI‐H) is yet to be fully elucidated. Materials and Methods: From February 2017 to February 2020, the data of patients with CRC who underwent next‐generation sequencing and had detailed record of clinicopathological information were investigated. HER2 alteration and its relationship with MSI‐H were analyzed. Results: Among 731 patients who underwent sequencing, 55 patients (7.5%) had HER2 alteration, including 29 (4.0%) with HER2 somatic mutations, 24 (3.3%) with HER2 gene amplification, and 2 patients (0.2%) with both HER2 mutations and amplification. R678Q was the most common mutated kinase domain, and no HER2 kinase domain in‐frame insertions/deletions were found in HER2 mutated cases. MSI‐H was found in 5.2% of our cohort and 36.8% of MSI‐H patients had HER2 mutation. For HER2 mutated cases, 48.3% were MSI‐H, whereas none of the HER2 amplification cases were MSI‐H. MSI‐H patients with HER2 mutation had significantly worse median progression‐free survival for programmed death‐1 (PD‐1) antibody than those without HER2 alteration (p =.036). Conclusion: High MSI‐H rate was found in HER2 mutated cases, but no MSI‐H was found in HER2 amplification cases. MSI‐H patients with HER2 mutated had worse progression‐free survival for PD‐1 antibody than those without. Implications for Practice: This study highlights the high microsatellite instability‐high (MSI‐H) rate in HER2 mutated cases but no MSI‐H in HER2 amplification cases. Moreover MSI‐H patients with HER2 mutated had worse progression‐free survival for programmed death‐1 antibody than those without. Further research to explore the internal relationship between HER2 alteration and MSI‐H is needed. The clinical significance of HER2 somatic mutations and its relationship with high microsatellite instability in colorectal cancer is not fully understood. This study investigated the relationship by analyzing data of patients with colorectal cancer who underwent next‐generation sequencing. [ABSTRACT FROM AUTHOR]

Phosphorus (P) limitation affects phytoplankton growth and population size in aquatic systems, and consequently limits aquatic primary productivity. Plants have evolved a range of metabolic responses to cope with P limitation, such as accumulation of purple acid phosphatases (PAPs) to enhance acquisition of phosphates. However, it remains unknown whether algae have evolved a similar mechanism. In this study, we examined the role of PAPs in the model microalga Phaeodactylum tricornutum. Expression of PAP1 was enhanced in P. tricornutum cells grown on organophosphorus compared to inorganic phosphate. PAP1 overexpression improved cellular growth and biochemical composition in a growth-phase dependent manner. PAP1 promoted growth and photosynthesis during growth phases and reallocated carbon flux towards lipogenesis during the stationary phase. PAP1 was found to be localized in the endoplasmic reticulum and it orchestrated the expression of genes involved in key metabolic pathways and translocation of inorganic P (Pi), thereby improving energy use, reducing equivalents and antioxidant potential. RNAi of PAP1 induced expression of its homolog PAP2 , thereby compensating for the Pi scavenging activity of PAP1. Our results demonstrate that PAP1 brings about sequential regulation of metabolism, and provide novel insights into algal phosphorus metabolism and aquatic primary productivity. [ABSTRACT FROM AUTHOR]

Aims Soil inorganic nitrogen (N) has long been recognized to play an important role in plant invasions. Whilst comparing the N use strategies of multiple invasive versus native plant congeners along an entire N gradient is key to understanding plant invasion success, there are few related studies. Methods We conducted a potted experiment with six invasive and native congeneric pairs, which were subjected to 11 nitrate/ammonium (NO3−/NH4+) ratios (i.e. 100% NO3− at one end and 100% NH4+ at the other end), each with low- and high-N levels. Each species–N combination was replicated eight times, and thus there were 2112 pots in total. We measured the following traits: the total biomass, growth advantage, biomass allocation, leaf chlorophyll content and low-N tolerance. Important Findings Invasive and native congeners grew well at any NO3−/NH4+ ratios, and their responses of growth, allocation and tolerance were approximately parallel along the 11 NO3−/NH4+ ratios across two N levels. Plant invaders grew larger and had greater chlorophyll contents, higher root biomass allocation and stronger low-N tolerance than their congeneric natives. These findings suggest that invasive and native plant congeners may utilize similar inorganic N forms (i.e. NO3− and NH4+) across an entire N composition gradient and that higher N use efficiencies could favor alien plants to invade new plant communities where congeneric natives are dominants. [ABSTRACT FROM AUTHOR]

Genomic imprinting is an epigenetic modification of DNA, whereby gene expression is restricted to either maternally or paternally inherited alleles. Imprinted genes (IGs) in the placenta and embryo are essential for growth regulation and nutrient supply. However, despite being an important nutrition delivery organ, studies on mammary gland genomic imprinting remain limited. In this study, we found that both the number of IGs and their expression levels decreased during development of the mouse mammary gland. IG expression was lineage-specific and related to mammary gland development and lactation. Meta-analysis of single-cell RNA sequencing data revealed that mammary gland IGs were co-expressed in a network that regulated cell stemness and differentiation, which was confirmed by our functional studies. Accordingly, our data indicated that IGs were essential for the self-renewal of mammary gland stem cells and IG decline was correlated with mammary gland maturity. Taken together, our findings revealed the importance of IGs in a poorly studied nutrition-related organ, i.e. the mammary gland, thus providing a reference for further studies on genomic imprinting. [ABSTRACT FROM AUTHOR]

Accumulating studies have shown that high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) may improve cognitive dysfunction of the patients with schizophrenia (SCZ), but with inconsistent results. The present study aims to assess the efficacy of different frequencies of neuronavigated rTMS in ameliorating cognitive impairments and alleviating the psychotic symptoms. A total of 120 patients were randomly assigned to 3 groups: 20 Hz rTMS (n = 40), 10 Hz rTMS (n = 40), or sham stimulation (n = 40) for 8 weeks, and then followed up at week 32. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to assess the cognitive functions of the patients at baseline, at the end of week 8, and week 32 follow-up. Psychotic symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS) at baseline and at the end of week 2, week 4, week 6, week 8, and week 32 follow-up. Our results demonstrated that 20 Hz rTMS treatment produced an effective therapeutic benefit on immediate memory of patients with chronic SCZ at week 8, but not in the 10 Hz group. Interestingly, both 10 Hz and 20 Hz rTMS treatments produced delayed effects on cognitive functions at the 6-month follow-up. Moreover, in both 10 Hz rTMS and 20 Hz rTMS, the improvements in RBANS total score were positively correlated with the reduction of PANSS positive subscore at the 6-month follow-up. Stepwise regression analysis identified that the visuospatial/constructional index, immediate memory index, and prolactin at baseline were predictors for the improvement of cognitive impairments in the patients. Our results suggest that add-on HF rTMS could be an effective treatment for cognitive impairments in patients with chronic SCZ, with a delayed effect. Trial registration: clinicaltrials.gov identifier—NCT03774927. [ABSTRACT FROM AUTHOR]

Syngnathids (seahorses, pipefishes and seadragons) exhibit an array of morphological innovations including loss of pelvic fins, a toothless tubular mouth and male pregnancy. They comprise two subfamilies: Syngnathinae and Nerophinae. Genomes of three Syngnathinae members have been analyzed previously. In this study, we have sequenced the genome of a Nerophinae member, the Manado pipefish (Microphis manadensis), which has a semi-enclosed brood pouch. Comparative genomic analysis revealed that the molecular evolutionary rate of the four syngnathids is higher than that of other teleosts. The loss of all but one P/Q-rich SCPP gene in the syngnathids suggests a role for the lost genes in dentin and enameloid formation in teleosts. Genome-wide comparison identified a set of 118 genes with parallel identical amino acid substitutions in syngnathids and placental mammals. Association of some of these genes with placental and embryonic development in mammals suggests a role for them in syngnathid pregnancy. [ABSTRACT FROM AUTHOR]

Background: Chlamydia trachomatis and Chlamydia muridarum are intracellular bacterial pathogens of mucosal epithelial cells. CD4 T cells and major histocompatibility complex (MHC) class II molecules are essential for protective immunity against them. Antigens presented by dendritic cells (DCs) expand naive pathogen-specific T cells (inductive phase), whereas antigens presented by epithelial cells identify infected epithelial cells as targets during the effector phase. We previously showed that DCs infected by C trachomatis or C muridarum present epitopes from a limited spectrum of chlamydial proteins recognized by Chlamydia-specific CD4 T cells from immune mice.Methods: We hypothesized that Chlamydia-infected DCs and epithelial cells present overlapping sets of Chlamydia-MHC class II epitopes to link inductive and effector phases to generate protective immunity. We tested that hypothesis by infecting an oviductal epithelial cell line with C muridarum, followed by immunoaffinity isolation and sequencing of MHC class I- and II-bound peptides.Results: We identified 26 class I-bound and 4 class II-bound Chlamydia-derived peptides from infected epithelial cells. We were surprised to find that none of the epithelial cell class I- and class II-bound chlamydial peptides overlapped with peptides presented by DCs.Conclusions: We suggest the discordance between the DC and epithelial cell immunoproteomes has implications for delayed clearance of Chlamydia and design of a Chlamydia vaccine. [ABSTRACT FROM AUTHOR]

This paper considers a matrix optimization problem where the objective function is continuously differentiable and the constraints involve a semidefinite-box constraint and a rank constraint. We first replace the rank constraint by adding a non-Lipschitz penalty function in the objective and prove that this penalty problem is exact with respect to the original problem. Next, for the penalty problem we present a nonmonotone proximal gradient (NPG) algorithm whose subproblem can be solved by Newton's method with globally quadratic convergence. We also prove the convergence of the NPG algorithm to a first-order stationary point of the penalty problem. Furthermore, based on the NPG algorithm, we propose an adaptive penalty method (APM) for solving the original problem. Finally, the efficiency of an APM is shown via numerical experiments for the sensor network localization problem and the nearest low-rank correlation matrix problem. [ABSTRACT FROM AUTHOR]

Objective: Identifying drug discontinuation (DDC) events and understanding their reasons are important for medication management and drug safety surveillance. Structured data resources are often incomplete and lack reason information. In this article, we assessed the ability of natural language processing (NLP) systems to unlock DDC information from clinical narratives automatically.Materials and Methods: We collected 1867 de-identified providers' notes from the University of Massachusetts Medical School hospital electronic health record system. Then 2 human experts chart reviewed those clinical notes to annotate DDC events and their reasons. Using the annotated data, we developed and evaluated NLP systems to automatically identify drug discontinuations and reasons at the sentence level using a novel semantic enrichment-based vector representation (SEVR) method for enhanced feature representation.Results: Our SEVR-based NLP system achieved the best performance of 0.785 (AUC-ROC) for detecting discontinuation events and 0.745 (AUC-ROC) for identifying reasons when testing this highly imbalanced data, outperforming 2 state-of-the-art non-SEVR-based models. Compared with a rule-based baseline system for discontinuation detection, our system improved the sensitivity significantly (57.75% vs 18.31%, absolute value) while retaining a high specificity of 99.25%, leading to a significant improvement in AUC-ROC by 32.83% (absolute value).Conclusion: Experiments have shown that a high-performance NLP system can be developed to automatically identify DDCs and their reasons from providers' notes. The SEVR model effectively improved the system performance showing better generalization and robustness on unseen test data. Our work is an important step toward identifying reasons for drug discontinuation that will inform drug safety surveillance and pharmacovigilance. [ABSTRACT FROM AUTHOR]

Background: The efficiency and mechanisms of adoptive transfer of cytomegalovirus (CMV)specific T cells for refractory CMV infection after haploidentical stem cell transplantation (haplo-SCT) remain largely unknown.Methods: Thirty-two patients with refractory CMV infection who accepted treatment with adoptive CMV-specific T-cell infusion following haplo-SCT were prospectively enrolled. Another 32 patients with nonrefractory CMV infection after haplo-SCT were selected as control subjects. The phenotypical and functional characteristics of CMV-specific T cells were analyzed before and after cellular therapy in the refractory cohort, as well as in the nonrefractory cohort.Results: In the refractory cohort, 27 of the 32 treated patients exhibited CMV clearance within 4 weeks after adoptive T-cell transfer without recurrence. The in vivo expansion of CMV-specific T cells and improvements in the cytokine production and proliferation ability of the CMV-specific T cells were observed after cellular therapy. Moreover, a reduced expression of programmed death-1 (PD-1) on CMV-specific T cells was observed. However, in the remaining 5 patients who showed CMV recurrence 4 weeks after transfer, neither the quantity nor the function of CMV-specific T cells was restored.Conclusions: The adoptive transfer of CMV-specific T cells promotes quantitative and functional recovery of CMV-specific T cells to guard against refractory CMV infection after haplo-SCT. [ABSTRACT FROM AUTHOR]

Background The poor prognosis of resectable esophageal squamous cell carcinoma (ESCC) poses an unmet need to identify genomic early predictive and prognostic biomarkers to improve treatment outcome and risk stratification. Methods Retrospective targeted sequencing was performed on 80 ESCC formalin-fixed, paraffin-embedded (FFPE) tumor specimens from 37 good responders and 43 poor responders receiving neoadjuvant treatment. Somatic mutations and copy number variations (CNVs) were detected in 130 cancer druggable genes with TOMA Os-seq. Kaplan Meier curve and COX regression analysis were used to estimate the risk of relapse and survival. Results Twelve patients (12/80, 15%) with hot spot NFE2L2 mutations occurred with significantly higher frequency in poor responders (p = 0.0003) and in patients with non-complete pathological response (p = 0.007) in resectable ESCC treated by chemo-radiotherapy (CRT). These patients also had poorer prognosis with higher risk of death (HR = 1.942, p = 0.039) and relapse (HR = 1.817, p = 0.063) by COX analysis. The independent prognostic role of hot spot NFE2L2 mutations was validated by the presence of recurrent plasma cell-free (ct)-DNA NFE2L2 mutations in an independent prospective cohort of resectable ESCC patients. Conclusions In summary, our study now demonstrates the clinical usefulness of hot spot NFE2L2 mutations, as a potential predictive and prognostic biomarker associated with pre-surgery CRT responses, and provides novel insights for future therapeutic options targeting the NRF signaling in resectable ESCC treated by neoadjuvant CRT. The novel prognostic role of hot spot NFE2L2 mutations may be useful markers to guide clinicians for treatment decisions in resectable ESCC patients following pre-surgery treatment. [ABSTRACT FROM AUTHOR]

Background Uncontrolled cell division is a hallmark of cancer, making targeting deregulated cell cycle molecules with prognostic significance a promising approach to combat tumorigenesis. Our research focuses on HAUS7, a molecule highly relevant to esophageal squamous cell carcinoma (ESCC), and its interaction with gamma-tubulin. We designed a novel peptide, HTIP1, to target this interaction and suppress tumorigenesis. Methods We investigated the clinical relevance of HAUS7 upregulation in ESCC cohorts, studied its physiological microtubule-regulating and tumorigenic functions in vitro and/or in vivo, and employed a multidisciplinary approach to decode the mechanism underlying HAUS7 suppression. HTIP1 was designed by structure modelling and docking simulation. Its properties, cancer selectivity, anti-tumor efficacy, off-target effect and mechanisms of action were comprehensively evaluated. Patient-derived tumor xenograft models were used to provide additional preclinical evidence. Results Our results show that HAUS7 is the most essential HAUS member for regulating microtubule dynamics in ESCC, and its overexpression is correlated with aggressive tumor phenotypes and poor prognosis. Mechanistically, HAUS7 suppression releases gamma-tubulin, which upon phosphorylation, seizes LMAN1 and together they re-localize to the nucleus. The removal of LMAN1 from its innate location triggers endoplasmic reticulum stress and apoptosis. We designed HTIP1 to perturb HAUS7/gamma-tubulin interaction, which demonstrated anti-tumor effects similar to HAUS7 suppression, with high tumor specificity, negligible off-target effects, and more potency than relevant compounds. Conclusions Our findings provide a new strategy to counter tumorigenesis and pave the way for the development of a new drug targeting the HAUS7/gamma-tubulin interaction. [ABSTRACT FROM AUTHOR]

Background Cancer cachexia is a metabolic and functional multifactorial body wasting syndrome and is one of the major causes of death in late-stage patients. Esophageal squamous cell carcinoma (ESCC) presents one of the highest morbidity and mortality rates due to cancer cachexia. However, there is limited effective and approved targeted treatment. Cancer cachexia animal models are highly limited, with few cancer types available as a pre-clinical drug testing platform and with none related to esophageal carcinoma. Methods We have developed a panel of ESCC patient-derived organoid xenograft (PDOX) mouse models based on our latest patient-derived organoid cultures from Hong Kong patients. Results Our PDOX mouse model displays cachexic phenotypes that traditional cell line-derived xenografts lack, including body wasting and functional signs. The slow-proliferating characteristic of the ESCC PDOX on mice allows development of cachexic conditions before the humane endpoint. Our comprehensive panel of PDOX lines allowed us to identify full spectrum and differential cachexia severities across mice bearing different PDOXs, indicating a heterogenous nature and allowing faithful mimicking of various patient conditions. Molecular analysis showed that several classic cachexia-related gene expressions were up-regulated in the isolated liver and inguinal adipose tissues of cachexic mice, along with elevated circulating Il-6 levels. Conclusion Our ESCC PDOX model potentially serves as a useful pre-clinical cachexia-targeted drug testing platform, providing more treatment options for ESCC patients for better disease management. Acknowledgments We acknowledge the Research Grants Council (Theme-based Research Scheme T12–701/17-R to MLL) and the Food and Health Bureau (Health and Medical Research Fund 06171566 to VZY) of the Hong Kong Special Administrative Region for funding support. We acknowledge DSMZ (German Collection of Microorganisms and Cell Culture) for the KYSE cell lines. We acknowledge the University of Hong Kong LKS Faculty of Medicine Centre for PanorOmic Sciences for providing imaging facilities. [ABSTRACT FROM AUTHOR]

Background An increasing number of clinical studies focus on investigating the use of immunotherapy in the treatment of esophageal cancer. This phase II trial (NEOCRTEC-2001 clinical trial) aimed to assess the safety and efficacy of sintilimab in combination with cisplatin and paclitaxel induction immunochemotherapy followed by surgery for locally advanced borderline-resectable esophageal squamous cell carcinoma (BR-ESCC). Methods Patients with primary tumor or bulky lymph nodes that might invade nearby organs were eligible. Treatment started with 2–4 cycles of induction immunochemotherapy, followed by surgery if the tumor was assessed resectable, or by radical concurrent chemoradiotherapy if unresectable. The primary endpoint was pathologically proven complete resection (R0) rate. The secondary end points included pathological complete response (pCR) rate, overall survival (OS), progression-free survival (PFS), adverse events and postoperative complication. Results From September 2020 to now, a total of 34 patients were enrolled. After immunochemotherapy, 21 patients (61.8%) received surgery and 13 (38.2%) did not. All patients underwent McKeown procedure, and median operation time was 295 minutes (range 201–489 minutes). All patients received esophageal reconstruction using gastric tube, and underwent cervical anastomosis. An average of 46.6 lymph nodes were dissected, and positive lymph nodes were observed in 5 of the 21 patients. R0 resection was confirmed in 20 patients (58.8%). One patient underwent R2 resection because of tumor invasion of the aorta. Pathologic complete response was confirmed in 6 patients (6/34, 17.6%), while 5 patients (5/34, 14.7%) had few or no regressive changes (TRG3). Conclusion The treatment strategy of induction immunochemotherapy followed by surgery is promising for patients with locally advanced borderline-resectable esophageal squamous cell carcinoma. The whole results of pathologic response and prognostic value are awaited with interest. [ABSTRACT FROM AUTHOR]

Background A phase 2 trial analyzed the safety and efficacy of TPF induction chemotherapy followed by surgery for locally advanced borderline-resectable esophageal squamous cell carcinoma (NEOCRTEC-1601 clinical trial). This study presents updated 3-year analyses to further characterize the impact of TPF chemotherapy followed by surgery. Methods Patients diagnosed with BR-ESCC because of the primary tumor or bulky lymph node that potentially invaded adjacent organs were eligible. The treatment started with TPF chemotherapy, followed by surgery if the cancer was resectable, or by concurrent chemoradiation if it was unresectable. This updated analysis presents the 2- and 3-year overall survival rates and progression-free survival rates. Results A total of 27 patients (57.4%) received surgery and R0 resection was confirmed in 25 patients (53.2%). Pathologic complete response was confirmed in 4 patients (8.5%). The median follow-up time for the patients surviving without death was 44.8 months (range, 3.4–74.6 months). The median OS for all patients was 41.9 months (95% CI 18.6–65.3), with a median PFS of 38.7 months (95% CI 23.5–53.9). The 3-year survival rate of all patients was 54.4%. The OS and PFS for R0 group patients were significantly longer than those in non-R0 group (median OS: undefined vs. 26.5 months, HR 0.38; 95% CI 0.17–0.85, P = 0.010; median PFS: undefined vs. 17.2 months, HR 0.41, 95% CI 0.18–0.91, P = 0.016). The 3-year survival rate was 65.4% for the R0 group patients compared with 40.3% for the non-R0 patients (HR 0.41, 95%CI 0.16–0.91, P = 0.034). Conclusions Long-term follow-up evaluation confirmed that TPF followed by surgery is feasible and promising in terms of survival for BR-ESCC patients. [ABSTRACT FROM AUTHOR]

Objective: We aim to evaluate the effectiveness of advanced deep learning models (eg, capsule network [CapNet], adversarial training [ADV]) for single-domain and multidomain relation extraction from electronic health record (EHR) notes.Materials and Methods: We built multiple deep learning models with increased complexity, namely a multilayer perceptron (MLP) model and a CapNet model for single-domain relation extraction and fully shared (FS), shared-private (SP), and adversarial training (ADV) modes for multidomain relation extraction. Our models were evaluated in 2 ways: first, we compared our models using our expert-annotated cancer (the MADE1.0 corpus) and cardio corpora; second, we compared our models with the systems in the MADE1.0 and i2b2 challenges.Results: Multidomain models outperform single-domain models by 0.7%-1.4% in F1 (t test P < .05), but the results of FS, SP, and ADV modes are mixed. Our results show that the MLP model generally outperforms the CapNet model by 0.1%-1.0% in F1. In the comparisons with other systems, the CapNet model achieves the state-of-the-art result (87.2% in F1) in the cancer corpus and the MLP model generally outperforms MedEx in the cancer, cardiovascular diseases, and i2b2 corpora.Conclusions: Our MLP or CapNet model generally outperforms other state-of-the-art systems in medication and adverse drug event relation extraction. Multidomain models perform better than single-domain models. However, neither the SP nor the ADV mode can always outperform the FS mode significantly. Moreover, the CapNet model is not superior to the MLP model for our corpora. [ABSTRACT FROM AUTHOR]

Background Few studies have investigated the effect of smoking on type 2 diabetes in women compared with men, even though several epidemiological studies provided a clear picture of the risk among the entire population. Methods We systematically searched PubMed and Embase up to August 2017 for prospective studies that were stratified by sex with measures of the relative risk (RR) for type 2 diabetes and current smoking compared with non-smoking. The sex-specific RRs and their ratios (RRRs), comparing women with man, were pooled using random-effects models. Results Seventeen articles were identified including 20 prospective cohorts with 5 077 289 participants and 223 084 incident cases of type 2 diabetes. The pooled RRR suggested a similar risk of type 2 diabetes associated with smoking in women compared with men (RRR: 0.98, 95% confidence interval [CI]: 0.96–1.01). Furthermore, no significant sex difference in the RR was found between former smokers and those who had never smoked (RRR: 0.98, 95% CI: 0.92–1.04). Conclusions The findings of this meta-analysis indicate that female smokers had similar risk of type 2 diabetes with male smokers. [ABSTRACT FROM AUTHOR]

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Tiller angle in cereals is a key shoot architecture trait that strongly influences grain yield. Studies in rice (Oryza sativa) have implicated shoot gravitropism in the regulation of tiller angle. However, the functional link between shoot gravitropism and tiller angle is unknown. Here, we conducted a large-scale transcriptome analysis of rice shoots in response to gravistimulation and identified two new nodes of a shoot gravitropism regulatory gene network that also controls rice tiller angle. We demonstrate that HEAT STRESS TRANSCRIPTION FACTOR 2D (HSFA2D) is an upstream positive regulator of the LAZY1-mediated asymmetric auxin distribution pathway. We also show that two functionally redundant transcription factor genes, WUSCHEL RELATED HOMEOBOX6 (WOX6) and WOX11 , are expressed asymmetrically in response to auxin to connect gravitropism responses with the control of rice tiller angle. These findings define upstream and downstream genetic components that link shoot gravitropism, asymmetric auxin distribution, and rice tiller angle. The results highlight the power of the high-temporal-resolution RNA-seq data set and its use to explore further genetic components controlling tiller angle. Collectively, these approaches will identify genes to improve grain yields by facilitating the optimization of plant architecture. [ABSTRACT FROM AUTHOR]

To date, PMN J2134-0419 (at a redshift z = 4.33) is the second most distant quasar known with a milliarcsecond-scale morphology permitting direct estimates of the jet proper motion. Based on two-epoch observations, we constrained its radio jet proper motion using the very long baseline interferometry (VLBI) technique. The observations were conducted with the European VLBI Network (EVN) at 5 GHz on 1999 November 26 and 2015 October 6. We imaged the central 10-pc scale radio jet emission and modelled its brightness distribution. By identifying a jet component at both epochs separated by 15.86 yr, a proper motion of μ = 0.035 ± 0.023 mas yr-1 is found. It corresponds to an apparent superluminal speed of βa = 4.1 ± 2.7 c. Relativistic beaming at both epochs suggests that the jet viewing angle with respect to the line of sight is smaller than 20°, with a minimum bulk Lorentz factor Γ = 4.3. The small value of the proper motion is in good agreement with the expectations from the cosmological interpretation of the redshift and the current cosmological model. Additionally we analysed archival Very Large Array observations of J2143-0419 and found indication of a bent jet extending to ∼30 kpc. [ABSTRACT FROM AUTHOR]

This study explores the mechanism of histone acetylation under the effect of oxidative stress in rat liver injury induced by isoniazid (INH). Fifty-six adult SD rats were selected and divided randomly into INH groups (48) and control (8). Rats in INH groups were intragastrically injected with 55 mg kg−1 day−1 for 3, 7, 10, 14, 21, and 28 days, and control rats were given an equal volume of distilled water. Pathological changes in liver tissues were observed by HE staining. Western blot analysis was conducted to measure the expression levels of H3k14ac and H4k8ac. The activities of HAT, HDAC and IL-1β, and TNF-α were detected by ELISA in liver tissues. Real-time RT-PCR analysis was performed to determine the protein expression levels of HAT, HDAC, and IL-1β and the mRNA expression of TNF-α. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were assayed by biochemical methods in liver tissues. At different time points, the SOD activity decreased, whereas the MDA content significantly increased after 14 days (FSOD = 11.15, FMDA = 7.42, P < 0.01). During this period, the expression of histone acetylated H3K14 and H4K8 acetylation decreased compared with the control group (FH3K14 = 4.18, FH4K8 = 3.87, P < 0.05); by contrast, HDAC1 and HDAC2 showed a high expression level compared with those in the control group (FHDAC1 = 29.13, FHDAC2 = 58.34, P < 0.01). Moreover, the expression of CBP/P300 was lower than that in the control group (FCBP/P300 = 12.18, P = 0.001), and the protein contents of IL-1β and TNF-α in rat liver tissues were up-regulated (FIL-1β = 44.88, FTNF-α = 41.56, P < 0.01). These results suggest that histone acetylation is involved in INH-induced rat liver injury. Furthermore, the hypoacetylation of histones H3K14 and H4K8 is negatively correlated with oxidative stress-mediated rat liver injury. [ABSTRACT FROM AUTHOR]

Parasenecio with c. 70 species is a major component of the eastern Asian Tussilagininae (Asteraceae, Senecioneae). Previous molecular phylogenetic studies, although with limited taxon sampling, have suggested that it is polyphyletic and forms a complex with ten other eastern Asian genera of Tussilagininae, i.e. the Ligularia-Cremanthodium- Parasenecio (LCP) complex. Here we sample Parasenecio and its relatives in the LCP complex densely and generate two phylogenetic hypotheses for the genus using four plastid DNA (trnCGCA-petN, trnGUCC-trnTGGU-psbD, trnTUGUtrnLUAA and rpl32-ndhF) and two nuclear ribosomal (nr)DNA [internal and external transcribed spacer (ITS and ETS)] regions, respectively. Analyses of the plastid DNA data produce a robust generic-level phylogenetic tree for Parasenecio and clearly demonstrate the polyphyletic pattern of the genus. Most notably, two sections of Parasenecio, P. section Delphiniifolii s.s. and P. section Taimingasa, are shown to be distantly related to core Parasenecio, being sister to Miricacalia and Syneilesis, respectively, with strong support. The small genus Sinacalia is also revealed to be polyphyletic, with S. caroli nested in core Parasenecio, and S. tangutica and S. davidii forming a clade sister to the core Parasenecio-S. caroli clade. The nrDNA tree is, however, relatively poorly resolved, only confirming the sister relationship between P. section Delphiniifolii s.s. and Miricacalia. Sinacalia s.s. is resolved as being deeply nested in core Parasenecio with nrDNA data, which is the only significant incongruence with the plastid DNA hypothesis relevant to the generic circumscription of Parasenecio. Statistical topology (approximately unbiased and Swofford- Olsen-Waddell-Hillis) tests suggest that, except for the position of Sinacalia s.s., the generic-level relationships of Parasenecio inferred from the plastid DNA data are not incongruent with those from the nrDNA data and, on the basis of current sequence data, the inferred molecular phylogenetic relationships should be preferred over the current classification. Based on these results and evidence from morphology and karyology, we propose a new circumscription of Parasenecio, involving transferring S. caroli to Parasenecio as P. caroli comb. nov. and segregating P. section Delphiniifolii s.s. and P. section Taimingasa as the new genera Japonicalia gen. nov. and Taimingasa gen. nov., respectively. Sinacalia s.s., with significant incongruence between the plastid DNA and nrDNA trees, is tentatively retained as an independent genus pending future studies. A revised key to Parasenecio and its close relatives is provided. [ABSTRACT FROM AUTHOR]

Plant architecture, a collection of genetically controlled agronomic traits, is one of the decisive factors that determine grain production. IDEAL PLANT ARCHITECTURE1 (IPA1) encodes a key transcription factor with pleiotropic effects on regulating plant architecture in rice (Oryza sativa), and IPA1 expression is controlled at the posttranscriptional level by microRNA156 and microRNA529. Here, we report the identification and characterization of IPA1 INTERACTING PROTEIN1 (IPI1), a RING-finger E3 ligase that can interact with IPA1 in the nucleus. IPI1 promotes the degradation of IPA1 in panicles, while it stabilizes IPA1 in shoot apexes. Consistent with these findings, the ipi1 loss-of-function mutants showed markedly altered plant architecture, including more tillers, enlarged panicles, and increased yield per plant. Moreover, IPI1 could ubiquitinate the IPA1-mediated complex with different polyubiquitin chains, adding K48-linked polyubiquitin chains in panicles and K63-linked polyubiquitin chains in the shoot apex. These results demonstrate that IPI1 affects plant architecture through precisely tuning IPA1 protein levels in different tissues in rice and provide new insight into the tissue-specific regulation of plant architecture and important genetic resources for molecular breeding. [ABSTRACT FROM AUTHOR]

Cisplatin and nedaplatin show significant antitumor activity and have been widely used for esophageal squamous cell carcinoma (ESCC). However, it is still unclear whether the efficacy and safety of nedaplatin-based regimens are comparable to those of cisplatin-based regimens in patients with metastatic/recurrent or advanced ESCC. Therefore, we conducted a systematic review and meta-analysis to compare the efficacy and safety of these two regimens for the treatment of metastatic/recurrent and advanced ESCC. We systematically searched Pubmed, Web of Science, and the Cochrane Database, as well as abstracts presented at conferences (all up to January 2015), for randomized-controlled and nonrandomized clinical trials that compared cisplatin-based and nedaplatin-based regimens in patients with metastatic/recurrent or advanced ESCC. Data were extracted from the original studies by two independent reviewers. This meta-analysis was performed usingReviewManager (RevMan)Version 5.3 (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014) software. Ten eligible trials, including 598 patients diagnosed with metastatic/recurrent or advanced ESCC, were included in our analysis. Our results demonstrated that the nedaplatin-based regimens were comparable to the cisplatin-based regimens in terms of overall survival (OS) (hazard ratio, HR: 1.22, 95% confidence interval, CI: 0.86-1.74, p=0.26) and overall response rate (ORR) (risk ratio, RR: 0.92, 95% CI: 0.77-1.10, p=0.37) and generated fewer grade 3 and 4 side effects including nausea (RR: 3.41, 95% CI: 1.67-6.96, p<0.001) and vomiting (RR: 3.62, 95% CI: 1.77-7.40, p<0.001) and fewer grade 1 and 2 adverse events including nausea (RR: 1.54, 95% CI: 1.23-1.93, p<0.001), vomiting (RR: 1.76, 95% CI: 1.76-2.30, p<0.001), peripheral neuropathy (RR: 1.75, 95% CI: 1.08-2.84, p=0.02) and renal dysfunction (creatinine) (RR: 3.28, 95% CI: 1.37-7.84, p=0.008). This systematic review and meta-analysis indicated that the efficacy of nedaplatin-based regimens was comparable to that of cisplatin-based regimens for patients with metastatic/recurrent or advanced ESCC, and that nedaplatin-based regimens were associated with less toxicity and better tolerability. However, this study was a meta-analysis of previously released data; therefore, there is a potential publication bias and heterogeneity among the included trials. Future, well-designed RCTs with large cohorts are warranted. [ABSTRACT FROM AUTHOR]