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To our knowledge, no randomised study has compared postmastectomy hypofractionated radiotherapy with conventional fractionated radiotherapy in patients with breast cancer. This study aimed to determine whether a 3-week schedule of postmastectomy hypofractionated radiotherapy is as efficacious and safe as a 5-week schedule of conventional fractionated radiotherapy. This randomised, non-inferiority, open-label, phase 3 study was done in a single academic hospital in China. Patients aged 18–75 years who had undergone mastectomy and had at least four positive axillary lymph nodes or primary tumour stage T3–4 disease were eligible to participate. Patients were randomly assigned (1:1) according to a computer-generated central randomisation schedule, without stratification, to receive chest wall and nodal irradiation at a dose of 50 Gy in 25 fractions over 5 weeks (conventional fractionated radiotherapy) or 43·5 Gy in 15 fractions over 3 weeks (hypofractionated radiotherapy). The modified intention-to-treat population (including all eligible patients who underwent randomisation but excluding those who were considered ineligible or withdrew consent after randomisation) was used in primary and safety analyses. The primary endpoint was 5-year locoregional recurrence, and a 5% margin was used to establish non-inferiority (equivalent to a hazard ratio <1·883). This trial is registered at ClinicalTrials.gov, number NCT00793962. Between June 12, 2008, and June 16, 2016, 820 patients were enrolled and randomly assigned to the conventional fractionated radiotherapy group (n=414) or hypofractionated radiotherapy group (n=406). 409 participants in the conventional fractionated radiotherapy group and 401 participants in the hypofractionated radiotherapy group were included in the modified intention-to-treat analyses. At a median follow-up of 58·5 months (IQR 39·2–81·8), 60 (7%) patients had developed locoregional recurrence (31 patients in the hypofractionated radiotherapy group and 29 in the conventional fractionated radiotherapy group); the 5-year cumulative incidence of locoregional recurrence was 8·3% (90% CI 5·8–10·7) in the hypofractionated radiotherapy group and 8·1% (90% CI 5·4–10·6) in the conventional fractionated radiotherapy group (absolute difference 0·2%, 90% CI −3·0 to 2·6; hazard ratio 1·10, 90% CI 0·72 to 1·69; p<0·0001 for non-inferiority). There were no significant differences between the groups in acute and late toxicities, except that fewer patients in the hypofractionated radiotherapy group had grade 3 acute skin toxicity than in the conventional fractionated radiotherapy group (14 [3%] of 401 patients vs 32 [8%] of 409 patients; p<0·0001). Postmastectomy hypofractionated radiotherapy was non-inferior to and had similar toxicities to conventional fractionated radiotherapy in patients with high-risk breast cancer. Hypofractionated radiotherapy could provide more convenient treatment and allow providers to treat more patients. National Key Projects of Research and Development of China; the Chinese Academy of Medical Science Innovation Fund for Medical Sciences; and Beijing Marathon of Hope, Cancer Foundation of China.

The aims of the present work were to isolate and characterize fungal endophytic communities associated with healthy wheat (Triticum aestivum L.) plants, collected from the North China. Segregated endophytes were screened for their PGP traits, abiotic stresses (heavy metals, salinity, drought, and temperature), and antibiotic sensitivity. A total of 16 endophytic fungi were isolated using the culture-dependent approach from different tissue parts of wheat plants. Based upon their internal transcribed spacer (ITS) rDNA gene sequencing, 15 out of 16 isolates were selected for further analysis. In the contemporary investigation, a number of the tested endophytes exhibited fairly good 1-aminocyclopropane-1-carboxylic acid deaminase (ACCD) (0.03±0.011 to 1.43±0.01 µmol α-KB mg−1 protein hr−1), indole acetic acid (IAA) (1.125±0.04 to36.12±0.004µgml−1), and phosphate solubilizing index (PSI) (2.08±0.03to5.16±0.36) activities. More than 30% isolates gave positive result for siderophore and ammonia tests, whereas all exhibited catalase activity but only 2 (582PDA1 and 582PDA11) produced hydrogen cyanide. Trichoderma strains showed salt, heavy metals, and drought tolerance at high levels and also exhibited resistance to all the tested antibiotics. Strain 582PDA4 was found to be the most temperature (55°C) tolerant isolate. The findings of this study indicated that the microbial endophytes isolated from wheat plants possessing a crucial function to improve plant growth could be utilized as biofertilizers or bioagents to establish a sustainable crop production system.

The Hengduan Mountains (HDM) biodiversity hotspot exhibits exceptional alpine plant diversity. Here, we investigate factors driving intraspecific divergence within a HDM alpine species Salix brachista (Cushion willow), a common component of subnival assemblages. We produce a high - quality genome assembly for this species and characterize its genetic diversity, population structure and pattern of evolution by resequencing individuals collected across its distribution. We detect population divergence that has been shaped by a landscape of isolated sky island-like habitats displaying strong environmental heterogeneity across elevational gradients, combined with population size fluctuations that have occurred since approximately the late Miocene. These factors are likely important drivers of intraspecific divergence within Cushion willow and possibly other alpine plants with a similar distribution. Since intraspecific divergence is often the first step toward speciation, the same factors can be important contributors to the high alpine species diversity in the HDM. Exceptional alpine plant diversity exists in the Hengduan Mountains. Here, through genome assembly and population genomics studies, the authors find notable intraspecific divergence among Cushion willow populations isolated by the sky island-like habitats and consider it contributes to speciation and biodiversity.

With the rapid development of energy storage systems in power supplies and electrical vehicles, the search for sustainable cathode materials to enhance the energy density of lithium‐ion batteries (LIBs) has become the focus in both academic and industrial studies. Currently, the widely utilized inorganic cathode materials suffer from drawbacks such as limited capacity, high energy consumption in production, safety hazards, and high‐cost raw materials. Therefore, it is necessary to develop green and sustainable cathode materials with higher specific capacity, better safety properties, and more abundant natural resources. As alternatives, organic cathode materials possess the advantages of high theoretical capacity, environmental friendliness, flexible structure design, systemic safety, and natural abundance, making them a promising class of energy storage materials. Herein, the development history of the organic cathode materials and recent research developments are reviewed, introducing several categories of typical organic compounds as cathode materials for LIBs, including conductive polymers, organosulfur compounds, radical compounds, carbonyl compounds, and imine compounds. The electrochemical performance, electrode reaction mechanism, and pros and cons of different organic cathode materials are comparatively analyzed to identify the challenges to be addressed. Finally, the future research and improvement directions of the organic cathode materials are also proposed. Organic cathode materials possess advantages such as high theoretical capacities, sustainability, structural designability, natural abundance, and low cost. Herein, the development history and recent achievements in typical organic cathode materials such as conductive polymers, organosulfur compounds, radical compounds, carbonyl compounds, and imine compounds, are summarized, emphasizing their working principle, structural design, performance comparison, remaining challenges, and future research directions.

Hirshleifer’s difference-form contest technology is a useful tool in the study of a class of conflict, especially military combats. We aim to highlight an important feature that the Hirshleifer contest model distinctively has, namely passivity (bidding zero effort) may stand as an effective choice in conflict even when the contest is highly deterministic (i.e., with small noise). For that purpose, we establish two propositions on the contest with n≥2 risk-neutral contestants under small noise. The first proposition states that every contestant bids arbitrarily close to zero (if not bidding zero with positive probability at all) under sufficiently small noise. The second proposition, more strikingly, states that every contestant either bids arbitrarily close to the second-highest valuation (among all the contestants’ valuations), or simply remains passive with certainty under any sufficiently small noise. We further show that the first proposition holds for the contest between risk-averse individuals endowed with constant absolute risk aversion as well, and illustrate by an example how quickly polarization in bidding among contestants, as is predicted by the propositions, may emerge as the noise of the contest abates. These results help pave the way toward a complete characterization of the difference-form contest.

Aim: The Himalaya-Hengduan Mountain (HHM) biodiversity hotspot including the 'sky islands' of Southwest China harbour exceptional plant diversity and endemicity at subnival summits (most of them exceeding 4300 m a.s.l.). This study is the first using a comparative phylogeographical framework to gain insights into the temporal origin of this highly fragmented subnival flora, and the historical factors shaping its genetic architecture as exemplified by four perennial herbs. Location: Himalaya-Hengduan Mountains, China. Methods: Based on nuclear and/or chloroplast (cp) DNA sequences for each of the four studied species, we performed AMOVA and mismatch distributional analyses to assess molecular structure, diversity and demographic history in relation to current and last glacial distributions using ecological niche modelling (ENM). Time-calibrated phylogenetic reconstructions of cpDNA data were used to infer species-specific stem and crown ages. Results: Our time estimates suggest that these species originated during the Late Pliocene or early-to-mid Pleistocene, whereas their onset of diversification generally falls into the mid-Pleistocene. All four species exhibited island-like population genetic structures, with all of them showing signatures of recent population growth and/or spatial expansion based on cpDNA. By contrast, ENM indicated that species broad-scale distributions remained fairly stable over the last glacial/post-glacial cycle. Main conclusions: The temporal origin of the four subnival HHM species is likely associated with tectonic changes in the region, while their near-simultaneous onset of diversification during the 'Naynayxungla Glaciation' (0.72-0.50 Ma) could reflect initial population divergence through climate-induced habitat fragmentation. Despite a rather stable distributional history, geographical population isolation and localized range expansion/contractions likely resulted in significant genetic structure and differentiation over the last glacial/post-glacial cycle. Overall, the present results are strongly indicative of shared evolutionary histories and phylogeographical structures among subnival plants from the 'sky island system' of the HHM region.

Purpose. To determine the intraexaminer repeatability and interexaminer reproducibility of tear meniscus height (TMH) and noninvasive Keratograph tear breakup time (NIKBUT) measurements obtained with the Keratograph 5M (K5M) in a sample of healthy and dry eye populations. Methods. Forty-two patients with dry eye disease (DED group) and 42 healthy subjects (healthy group) were recruited in this prospective study. In all subjects, each eye received 3 consecutive measurements using the K5M for the TMH and NIKBUTs (NIKBUT-first and NIKBUT-average). And then a different examiner repeated the measurements. The repeatability and reproducibility of measurements were assessed by the coefficient of variation (CV) and intraclass correlation coefficient (ICC). Results. The repeatability and reproducibility of TMH and NIKBUTs were good in both DED and healthy groups (CV% ≤ 26.1% and ICC ≥ 0.75 for all measurements). Patients with DED showed better intraexaminer repeatability for NIKBUTs, but worse for TMH than healthy subjects. Average TMH, NIKBUT-first, and NIKBUT-average were significantly lower in DED group than in healthy group (all P values < 0.05). Conclusions. Measurements of TMH and NIKBUTs obtained with the K5M may provide a simple, noninvasive screening test for dry eye with acceptable repeatability and reproducibility. The NIKBUTs were more reliable, but TMH was less reliable in patients with DED.

A better understanding of tree‐based intercropping effects on soil physicochemical properties and bacterial community has a potential contribution to improvement of agroforestry productivity and sustainability. In this study, we investigated the effects of mulberry/alfalfa intercropping on soil physicochemical properties and soil bacterial community by MiSeq sequencing of bacterial 16S rRNA gene. The results showed a significant increase in the contents of available nitrogen, available phosphate, available potassium, and total carbon in the rhizosphere soil of the intercropped alfalfa. Sequencing results showed that intercropping improved bacterial richness and diversity of mulberry and alfalfa based on richness estimates and diversity indices. The relative abundances of Proteobacteria, Actinobacteria, and Firmicutes were significantly higher in intercropping mulberry than in monoculture mulberry; and the abundances of Proteobacteria, Bacteroidetes, and Gemmatimonadetes in the intercropping alfalfa were markedly higher than that in monoculture alfalfa. Bacterial taxa with soil nutrients cycling were enriched in the intercropping system. There were higher relative abundances of Bacillus (0.32%), Pseudomonas (0.14%), and Microbacterium (0.07%) in intercropping mulberry soil, and Bradyrhizobium (1.0%), Sphingomonas (0.56%), Pseudomonas (0.18%), Microbacterium (0.15%), Rhizobium (0.09%), Neorhizobium (0.08%), Rhodococcus (0.06%), and Burkholderia (0.04%) in intercropping alfalfa soil. Variance partition analysis showed that planting pattern contributed 26.7% of the total variation of bacterial community, and soil environmental factors explained approximately 56.5% of the total variation. This result indicated that the soil environmental factors were more important than the planting pattern in shaping the bacterial community in the field soil. Overall, mulberry/alfalfa intercropping changed soil bacterial community, which was related to changes in soil total carbon, available phosphate, and available potassium. The effects of the basic factors (soil characteristics) and the operational factor (planting pattern) on the distribution of soil bacterial communities

Excessive visceral adipose tissue (VAT) has proven to be an efficient predictor of cardiovascular disease (CVD), independent of body mass index (BMI) or total body fat, and reducing visceral obesity is key to addressing the current epidemic of CVD. Selenium (Se) is suggested to protect against CVD, but a direct link between dietary Se intake and VAT levels is lacking. This study investigated this relationship, emphasizing the importance of expressing Se intake relative to body weight. A total of 3244 individuals participated in the Complex Diseases in the Newfoundland population: Environment and Genetics (CODING) study. Dietary Se intake was assessed using the Willett food frequency questionnaire (FFQ). VAT mass and VAT volume were precisely measured via dual-energy X-ray absorptiometry (DXA). Visceral adiposity, as indicated by VAT mass and VAT volume, decreased significantly across increasing quartiles of dietary Se intake (µg/kg/d) in both sexes. Compared with participants in the lowest quartile, those in the highest quartile had substantially lower visceral adiposity with reduction of 50.97% in women, and 63.75% in men, respectively. Likewise, this inverse dose-dependent manner was also observed when dietary Se intake was expressed as µg/d. Moreover, a linear negative correlation between dietary Se intake (µg/kg/d) and visceral adiposity was discovered, whereas no significant correlation was found if dietary Se intake was expressed as µg/d. After controlling for possible confounders, the linear regression analyses revealed that a 10% increase in dietary Se intake (µg/kg/d) was associated with 2.73% decrease in visceral adiposity. Interestingly, this inverse correlation remained consistent across different sex, age and menopausal status subgroups, with greater associations observed in males, individuals younger than 35 years old, and women in menopausal status. This is the first study to demonstrate a significant inverse association between dietary Se intake and VAT, which is exclusively evident when intake is expressed relative to body weight (µg/kg/d). This finding resolves prior inconsistencies and suggests that ensuring adequate weight-adjusted Se intake could be a valuable nutritional strategy for reducing visceral obesity and improving CVD prevention.

BackgroundEmerging evidence suggested that miRNAs can function as oncogenes or tumor suppressors by regulating downstream target genes. miR-324-3p has been reported to function in several carcinomas, but its role in gastric cancer (GC) is still unknown. This study aims to explore the effects of miR-324-3p on the development of GC.MethodsExpression of miR-324-3p was examined in GC cells and tissues by qRT-PCR. Effects of miR-324-3p on GC cells were evaluated by cell vitality assay, colony formation assay, cell migration assay, and flow cytometric assay. The dual luciferase assay was used to verify whether miR-324-3p could interact with the potential target genes. Western blot was used to assess the expression level of Smad4 and beta-catenin. Intracellular ATP level was also examined. The tumor xenografts were established using nude mice. A gastric organoid model was made from fresh stomach tissue.ResultsmiR-324-3p was expressed at higher levels in the tumor tissues compared with adjacent normal tissues. Overexpression of miR-324-3p promoted cell growth, migration, and decreased apoptosis. miR-324-3p repressed the expression of Smad4, and loss of Smad4 activated the Wnt/beta-catenin signaling pathway. Overexpression of Smad4 rescued the effects of miR-324-3p on GC cells. The intracellular ATP level was upregulated with overexpression of miR-324-3p. miR-324-3p facilitated tumor cell colonization and growth in vivo and contributed to the growth of gastric organoids.ConclusionsThe results suggested that miR-324-3p promoted GC through activating the Smad4-mediated Wnt/beta-catenin signaling pathway. The miR-324-3p/Smad4/Wnt signaling axis may be a potential therapeutic target to prevent GC progression.