The laurel family within the Magnoliids has attracted attentions owing to its scents, variable inflorescences, and controversial phylogenetic position. Here, we present a chromosome-level assembly of ...the Litsea cubeba genome, together with low-coverage genomic and transcriptomic data for many other Lauraceae. Phylogenomic analyses show phylogenetic discordance at the position of Magnoliids, suggesting incomplete lineage sorting during the divergence of monocots, eudicots, and Magnoliids. An ancient whole-genome duplication (WGD) event occurred just before the divergence of Laurales and Magnoliales; subsequently, independent WGDs occurred almost simultaneously in the three Lauralean lineages. The phylogenetic relationships within Lauraceae correspond to the divergence of inflorescences, as evidenced by the phylogeny of FUWA, a conserved gene involved in determining panicle architecture in Lauraceae. Monoterpene synthases responsible for production of specific volatile compounds in Lauraceae are functionally verified. Our work sheds light on the evolution of the Lauraceae, the genetic basis for floral evolution and specific scents.
Abstract
Background
Adding radiotherapy (RT) to systemic therapy improves progression-free survival (PFS) and overall survival (OS) in oligometastatic non-small cell lung cancer (NSCLC). Whether ...these findings translate to epidermal growth factor receptor (EGFR)–mutated NSCLC remains unknown. The SINDAS trial (NCT02893332) evaluated first-line tyrosine kinase inhibitor (TKI) therapy for EGFR-mutated synchronous oligometastatic NSCLC and randomized to upfront RT vs no RT; we now report the prespecified interim analysis at 68% accrual.
Methods
Inclusion criteria were biopsy-proven EGFR-mutated adenocarcinoma (per amplification refractory mutation system or next generation sequencing), with synchronous (newly diagnosed, treatment naïve) oligometastatic (≤5 metastases; ≤2 lesions in any one organ) NSCLC without brain metastases. All patients received a first-generation TKI (gefitinib, erlotinib, or icotinib), and randomization was between no RT vs RT (25-40 Gy in 5 fractions depending on tumor size and location) to all metastases and the primary tumor/involved regional lymphatics. The primary endpoint (intention to treat) was PFS. Secondary endpoints included OS and toxicities. All statistical tests were 2-sided.
Results
A total of 133 patients (n = 65 TKI only, n = 68 TKI with RT) were enrolled (2016-2019). The median follow-up was 23.6 months. The respective median PFS was 12.5 months vs 20.2 months (P < .001), and the median OS was 17.4 months vs 25.5 months (P < .001) for TKI only vs TKI with RT. Treatment yielded no grade 5 events and a 6% rate of symptomatic grade 3-4 pneumonitis in the TKI with RT arm. Based on the efficacy results of this prespecified interim analysis, the ethics committee recommended premature cessation of this trial.
Conclusions
As compared with a first-line TKI alone, addition of upfront local therapy using RT statistically significantly improved PFS and OS for EGFR-mutated NSCLC.
Systemic inflammation and immune dysfunction have been proved to be associated with cancer progression and metastasis in various malignancies. The aim of this retrospective study was to evaluate the ...prognostic significance of pre-treatment systemic immune-inflammation index (SII) in patients with advanced pancreatic cancer.
In total, 419 patients diagnosed with advanced pancreatic cancer, between January 2011 and December 2015, were retrospectively enrolled. The SII was developed based on a training set of 197 patients from 2011 to 2013 and validated in an independent cohort of 222 patients from 2014 to 2015. Data on baseline clinicopathologic characteristics; pre-treatment laboratory variables such as absolute neutrophil, lymphocyte, and platelet counts; and carbohydrate antigen 19-9 (CA19-9), total bilirubin (TBIL), albumin (ALB), alkaline phosphatase (ALP), alanine transaminase (ALT), and aspartate transaminase (AST) levels were collected. The association between clinicopathologic characteristics and SII was assessed. The overall survival was calculated using the Kaplan-Meier survival curves and compared using the log-rank test. Univariate and multivariate Cox proportional hazard regression models were used to analyze the prognostic value of the SII.
An optimal cutoff point for the SII of 440 stratified the patients with advanced pancreatic cancer into high (> 440) and low (≤ 440) SII groups in the training cohort. Univariate and multivariate analyses revealed that the SII was an independent predictor for overall survival. The prognostic significance of the SII was confirmed in both normal and elevated CA19-9 levels.
The baseline SII serves as an independent prognostic marker for patients with advanced pancreatic cancer and can be used in patients with both normal and elevated CA19-9 levels.
Heteroblasty refers to a phenomenon that a plant produces morphologically or functionally different lateral organs in an age‐dependent manner. In the model plant Arabidopsis thaliana, the production ...of trichomes (epidermal leaf hairs) on the abaxial (lower) side of leaves is a heteroblastic mark for the juvenile‐to‐adult transition. Here, we show that the heteroblastic development of abaxial trichomes is regulated by a spatiotemporally regulated complex comprising the leaf abaxial fate determinant (KAN1) and the developmental timer (miR172‐targeted AP2‐like proteins). We provide evidence that a short‐distance chromatin loop brings the downstream enhancer element into close association with the promoter elements of GL1, which encodes a MYB transcription factor essential for trichome initiation. During juvenile phase, the KAN1‐AP2 repressive complex binds to the downstream sequence of GL1 and represses its expression through chromatin looping. As plants age, the gradual reduction in AP2‐like protein levels leads to decreased amount of the KAN1‐AP2 complex, thereby licensing GL1 expression and the abaxial trichome initiation. Our results thus reveal a novel molecular mechanism by which a heteroblastic trait is governed by integrating age and leaf polarity cue in plants.
Synopsis
Age‐dependent development of leaf hairs (trichomes) on the abaxial (lower) leaf surface in Arabidopsis is regulated by integration of positional and temporal cues via a transcriptional complex comprising the leaf abaxial fate determinant KAN1 and the AP2‐like transcription factor TOE1 acting as a developmental timer.
AP2‐like proteins, including TOE1, repress abaxial trichome formation in juvenile leaves.
TOE1 forms a repressive complex with KAN1.
KAN1‐ complex binds to the 3′ downstream sequence of GL1, a master regulator of leaf trichome production.
KAN1/TOE1 represses GL1 expression through chromatin‐loop mediated histone deacetylation.
Regulated association of leaf polarity regulator KAN1 and AP2‐like transcription factor TOE1 represses leaf trichome formation in juvenile leaves via chromatin‐based mechanisms.
Rhizoma Alismatis (RA), the dried rhizome of Alisma orientale (Sam.) Juzep, is a common traditional herbal medicine named Ze Xie in Chinese. RA is an important herbal component of a number of ...well‐known Chinese medicinal preparations. It has been used to treat various ailments, such as dysuria, edema, nephropathy, hyperlipidemia, and diabetes. A wide range of chemical compounds, mainly triterpenoids, sesquiterpenoids, and diterpenoids, have been isolated from RA; among which the protostane‐type triterpenoids, termed alisols, have attracted the most attention owing to their unique chemical structures and various biological activities. The extract and active compounds of RA possess a wide spectrum of pharmacological effects (e.g., diuretic, antimetabolic disorder, hepatoprotective, immunomodulatory, antiosteoporotic, anti‐inflammatory, antitumor, antibacterial, and antiviral activities). Previous toxicological evaluations indicated that the RA extracts are relatively safe and have no serious side effects within certain dose ranges. This paper reviews the up‐to‐date information on the ethnomedicinal application, phytochemistry, pharmacology, and toxicology of RA. This information will be useful for a better understanding of the therapeutic potential of RA.
Low-color-temperature light-emitting diodes (LEDs) (called 1900 K LEDs for short) have the potential to become a healthy light source due to their blue-free property. Our previous research ...demonstrated that these LEDs posed no harm to retinal cells and even protected the ocular surface. Treatment targeting the retinal pigment epithelium (RPE) is a promising direction for age-related macular degeneration (AMD). Nevertheless, no study has evaluated the protective effects of these LEDs on RPE. Therefore, we used the ARPE-19 cell line and zebrafish to explore the protective effects of 1900 K LEDs. Our results showed that the 1900 K LEDs could increase the cell vitality of ARPE-19 cells at different irradiances, with the most pronounced effect at 10 W/m
. Moreover, the protective effect increased with time. Pretreatment with 1900 K LEDs could protect the RPE from death after hydrogen peroxide (H
O
) damage by reducing reactive oxygen species (ROS) generation and mitochondrial damage caused by H
O
. In addition, we preliminarily demonstrated that irradiation with 1900 K LEDs in zebrafish did not cause retinal damage. To sum up, we provide evidence for the protective effects of 1900 K LEDs on the RPE, laying the foundation for future light therapy using these LEDs.
Tumorigenesis is a complex and dynamic process, consisting of three stages: initiation, progression, and metastasis. Tumors are encircled by extracellular matrix (ECM) and stromal cells, and the ...physiological state of the tumor microenvironment (TME) is closely connected to every step of tumorigenesis. Evidence suggests that the vital components of the TME are fibroblasts and myofibroblasts, neuroendocrine cells, adipose cells, immune and inflammatory cells, the blood and lymphatic vascular networks, and ECM. This manuscript, based on the current studies of the TME, offers a more comprehensive overview of the primary functions of each component of the TME in cancer initiation, progression, and invasion. The manuscript also includes primary therapeutic targeting markers for each player, which may be helpful in treating tumors.
The presence of antibiotics in aquatic environments has attracted global concern. The Fenton system is one of the most popular methods for eliminating antibiotics in aquatic environments, but the ...existing Fenton system is limited due to the potential for secondary pollution, and the narrow pH range (∼3-5). In this study, we report that the bottlenecks for high-strength tetracycline (TC) wastewater treatment under neutral conditions can be tackled well by a class of mixed-valence W/Mo containing oxides (WMoO-x) with tunable morphologies. Triethanolamine was selected as a structure-directing agent to control the morphologies of the catalysts going from ultrathin nanowires (UTNWs) to wire-tangled nanoballs (WTNBs). As a proof of concept, the most efficient catalyst in the batch samples, WMoO-1 ultrathin nanowires, was employed as a model material for TC degradation, in which the coordinatively unsaturated metal atoms with oxygen defects serve as the sites for TC chemisorption and electron transfer. As a result, 91.75% of TC was degraded in 60 min for the initial TC concentration of 400 μM. Furthermore, LC-MS analysis confirmed that the TC could be degraded to nontoxic by-products without benzene rings, and finally mineralized to CO2 and H2O. ICP-MS and cycle experiments showed the good stability and reusability of WMoO-1 UTNWs in the Fenton-like system. The findings of this work provide fresh insights into the design of nanoscale catalyst morphology and reaffirm the versatility of doping in tuning catalyst activity, extending the range of the optimal pH values to neutral conditions. This is significant for the expansion of the heterogeneous Fenton-like family and its application in the field of water treatment.
Non-Hermitian quantum many-body systems are a fascinating subject to be explored. Using the generalized density matrix renormalization group method and complementary exact diagonalization, we ...elucidate the many-body ground states and dynamics of a 1D interacting non-Hermitian Aubry-André-Harper model for bosons. We find stable ground states in the superfluid and Mott-insulating regimes under wide range of conditions in this model. We reveal a skin superfluid state induced by the non-Hermiticity from the nonreciprocal hopping. We investigate the topology of the Mott-insulating phase and find its independence of the non-Hermiticity. The topological Mott insulators in this non-Hermitian system are characterized by four equal Chern numbers and a quantized shift of biorthogonal many-body polarizations. Furthermore, we show generic asymmetric expansion and correlation dynamics in the system.
Idiopathic pulmonary arterial hypertension (IPAH) is a rare disease with high heritability. Although several predisposing genes have been linked to IPAH, the genetic aetiology remains unknown for a ...large number of IPAH cases.
We conducted an exome-wide gene-based burden analysis on two independent case-control studies, including a total of 331 IPAH cases and 10 508 controls. Functional assessments were conducted to analyse the effects of genetic mutations on protein biosynthesis and function.
The gene encoding human bone morphogenetic protein 9 (
) was identified as a novel genetic locus displaying exome-wide association with IPAH in the discovery cohort (OR 18.8; p=1.9×10
). This association was authenticated in the independent replication cohort (p=1.0×10
). Collectively, the rare coding mutations in
occurred in 6.7% of cases, ranking this gene second to
, comprising a combined significance of 2.7×10
(OR 21.2). Intriguingly, the patients with
mutations had lower plasma levels of BMP9 than those without. Functional studies showed that the
mutations led to reduced BMP9 secretion and impaired anti-apoptosis ability in pulmonary arterial endothelial cells.
We identify
as an IPAH culprit gene.