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Rhodiola, belonging to the Crassulaceae family, is a perennial herbaceous plant genus. There are about 90 Rhodiola species worldwide, some of which have been reported to have medicinal properties. Rhodiola sachalinensis is a perennial medicinal herb within this genus and, in the present study, its chloroplast genome was sequenced, assembled, annotated and compared with 24 other Rhodiola species. The results obtained show that the chloroplast genome of R. sachalinensis is 151 595 bp long and has a CG content of 37.7%. The inverted repeats (IR) region of the Rhodiola chloroplast genome is the most conserved region, with the main differences being observed in the ycf1 and ndhF genes at the IRb‐small single copy boundary, and rps19 and trnH genes at the IRa‐large single copy boundary. Phylogenetic analysis showed that Rhodiola species form two major clades, and species with recorded medicinal properties, clustered together in one branch except for R. dumulosa. Within the genus, R. sachalinensis is most closely related to Rhodiola rosea, although comparative analyses showed that only R. sachalinensis and Rhodiola subopposita contained the psbZ gene, which encodes a highly conserved protein subunit of the Photosystem II core complex. Overall, the present study contributes to the understanding of the chloroplast genome of Rhodiola species, and provides a theoretical basis for the study of their genetic diversity and possible use as medicinal plants.

Abstract Epidermal growth factor receptor (EGFR) is reportedly overexpressed in most esophageal squamous cell carcinoma (ESCC) patients, but anti-EGFR treatments offer limited survival benefits. Our preclinical data showed the promising antitumor activity of afatinib in EGFR-overexpressing ESCC. This proof-of-concept, phase II trial assessed the efficacy and safety of afatinib in pretreated metastatic ESCC patients (n = 41) with EGFR overexpression (NCT03940976). The study met its primary endpoint, with a confirmed objective response rate (ORR) of 39% in 38 efficacy-evaluable patients and a median overall survival of 7.8 months, with a manageable toxicity profile. Transcriptome analysis of pretreatment tumors revealed that neurotrophic receptor tyrosine kinase 2 (NTRK2) was negatively associated with afatinib sensitivity and might serve as a predictive biomarker, irrespective of EGFR expression. Notably, knocking down or inhibiting NTRK2 sensitized ESCC cells to afatinib treatment. Our study provides novel findings on the molecular factors underlying afatinib resistance and indicates that afatinib has the potential to become an important treatment for metastatic ESCC patients.

Abstract Despite the crucial role of the Southern Hemisphere (SH) westerlies in modulating modern and past climate evolution, little is known about their behavior and possible forcing mechanisms during the early Cenozoic. We probe changes in the hydroclimate of southwest Australia during 62–51 Ma, based on sedimentary proxy records from the International Ocean Discovery Program Site U1514 in the Mentelle Basin. Our results reveal a transition from a less humid climate to wetter conditions at mid–high latitudes starting from the early Eocene, which suggests poleward migration of the SH westerlies. This long‐term trend is punctuated by short‐lived events of aridification during the Mid‐Paleocene Biotic Event and wetter intervals during the Paleocene‐Eocene Thermal Maximum, indicating additional short‐term meridional shifting of the westerlies. We propose that the evolution of SH westerlies was driven by the equator‐to‐pole temperature gradient regulated by global warming and ephemeral growth of the Antarctic ice sheet.

Citri Reticulatae Pericarpium(CRP) and Polygalae Radix (PR) are traditional Chinese medicinal herbs and dietary supplements, and they are commonly included in most prescriptions. Fungal contamination in CRP and PR has long been a concern for the public. Thus, in this study, the fungal diversity and abundance in CRP and PR were investigated via high-throughput sequencing technology. Analysis was conducted to determine the differences in dominant fungal microbiomes between mouldy and nonmouldy samples, and the correlation between the total number of fungi and fungal diversity in medicinal herbs at different altitudes and latitudes with other research was explored. Results show the fungal contamination of all 12 samples. At the phylum level, Ascomycota prevailed the most in CRP and PR with relative abundances of 56.96%–99.26% and 23.28%–76.06%, respectively. The dominant genera in CRP comprised Xeromyces (2.57%–53.21%), Aspergillus (0.18%–23.04%), Cystofilobasidium (0.032%–28.03) and Xerochrysium (0.31%–34.41%). The dominant genera in PR included Wallemia (0.27%–56.20%), Aspergillus (2.03%–48.06%), Xeromyces (0.20%–48.28%) and Xerochrysium (0.093%–43.95%). Two potential toxigenic fungi were detected: Alternaria alternata and Aspergillus versicolor. In addition, combined with the results of previous studies, the findings reveal the possible relation of diversity and abundance of fungal species to altitude and latitude: As the altitude and latitude decrease, the diversity and abundance of fungal species may increase. In conclusion, for the first time, this study focused on altitude and latitude as indicators and integrated multiple research findings to explore the correlation between the total amount and diversity of fungal species in the two edible herbs. Results reveal the fungal contamination of the surfaces of CRP and PR and provide a theoretical basis for the prevention and control of their fungal contamination.

Abstract Homologous recombination deficiency (HRD) testing has been approved by FDA for selecting epithelial ovarian cancer (EOC) patients who may benefit from the first-line poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance therapy. However, the effects of HRD on the clinical outcomes of first-line chemotherapy and first-line PARPi maintenance therapy have not been rigorously evaluated in Chinese EOC patients. Here, we developed an HRD assay and applied it to two large retrospectively collected Chinese EOC patient cohorts. In the first-line adjuvant chemotherapy cohort (FACT, N = 380), HRD status significantly improved PFS (median, 15.6 months vs. 9.4 months; HR, 0.688; 95% CI, 0.526–0.899; P = 0.003) and OS (median, 89.5 months vs. 60.9 months; HR, 0.636; 95% CI, 0.423–0.955; P = 0.008). In the first-line PARPi maintenance therapy cohort (FPMT, N = 83), HRD status significantly improved PFS (median, NA vs. 12 months; HR, 0.438; 95% CI, 0.201–0.957; P = 0.033) and OS (median, NA vs. NA months; HR, 0.12; 95% CI, 0.029–0.505; P = 0.001). Our results demonstrate that HRD status is a significant predictor for PFS and OS in both first-line chemotherapy and first-line PARPi maintenance therapy, providing strong real-world evidence for conducting genetic testing and improving clinical recommendations for Chinese EOC patients.

Understanding the paleoclimate responses in Southern Ocean and its surrounding land can help us to better explore the major climate transition mechanisms in geological history and predict the response ofthe earth system to abrupt climate changes in the future, while, there is still a lack of research on the paleoclimatere sponse of the surrounding land in Southern Ocean.Based on the age framework, major, traceand rare earth element compositions of the deep-sea sediments at Site U1516 of the International Ocean Discovery Program (IODP) 369, we determined that the sediments were mainly from the southwest continent of Australia, and then reconstructed the chemical weathering history of the source area on the tectonic time scale.In addition, we combined with the previous research results to discuss the paleoclimate evolution of continents surrounding Southern Ocean during the Late Eocene-Oligocene climate transition period and its response toglobal climate changes and regional paleogeographic changes.During the Eocene-Oligocene transition (e.g., 34.1 to 33.6 Ma and 31.3 to 29.8 Ma), the paleoclimate in the source area was mainly controlled by the significant changes in the paleogeographic pattern of the adjacent area, which was characterized by the climate conditions tending to bedry and cold and the decrease of chemical weathering intensity on the land surface.During the period of 33.6 to 31.3 Ma and 29.8 to 25.2 Ma, the palaeoclimate of the source area mainly responded to global climate changes.In theformer stage, the paleoclimate changed from dry and cold to wet and hot, the intensity of chemical weathering on the land surface increased correspondingly; In the latter stage, the climate maintained in a relatively stable dry and cold state, the intensity of chemical weathering on the land surface is also weak.

Wave–current interaction in coastal regions is significant and complicated. Most wave models consider the influence of ocean current and water depth on waves, while the influence of the gradient of the sea bottom slope is not taken into account in most research. This study aimed to analyze and quantify the contribution of storm tidal currents to coastal ocean waves in a case where sea bottom slope was not ignored. Fourier analysis was applied to solve the governing equation and boundary conditions, and an analytic model for the calculation of the variation of amplitude of wave orbital motion was proposed. Ocean currents affect ocean waves through resonance. In this paper, an implemented instance of this analytic model was given, using the Shengsi area during Typhoon Malakas as an example. The results suggest that vertical variation in the amplitude of wave orbital motion is remarkable. The impact of wave–current interaction is noticeable where the gradient of the sea bottom slope is relatively large.

The light curve period of an asteroid plays an important role in determining the rotation period, the collision evolution and the YORP effect. There are many period extraction algorithms used to find the light curve period of asteroids with long term observation, which are mainly based on the frequency, time and time–frequency domains. This paper presents a comprehensive and unparalleled comparison of the popular algorithms based on the DAMIT (Database of Asteroid Models from Inversion Techniques) data set to show the statistical results. Considering the quoted period, absolute magnitude, diameter, albedo, time span and number of observations, we analyze the accuracy of five popular methods using the light curve data of 2902 asteroids. We find that although the performance of all the algorithms varies little, Phase Dispersion Minimization (PDM) performs better, followed by Lomb-Scargle (LS), while Conditional Entropy (CE) is not better than the others under certain conditions. We also analyze the cases which are more suitable for searching by frequencies or by periods.

We propose two new ocean wind retrieval models for right circular-vertical (RV) and right circular-horizontal (RH) polarizations respectively from the compact-polarimetry (CP) mode of the RADARSAT Constellation Mission (RCM), which is scheduled to be launched in 2019. For compact RV-polarization (right circular transmit and vertical receive), we build the wind retrieval model (denoted CoVe-Pol model) by employing the geophysical model function (GMF) framework and a sensitivity analysis. For compact RH polarization (right circular transmit and horizontal receive), we build the wind retrieval model (denoted the CoHo-Pol model) by using a quadratic function to describe the relationship between wind speed and RH-polarized normalized radar cross-sections (NRCSs) along with radar incidence angles. The parameters of the two retrieval models are derived from a database including wind vectors measured by in situ National Data Buoy Center (NDBC) buoys and simulated RV- and RH-polarized NRCSs and incidence angles. The RV- and RH-polarized NRCSs are generated by a RCM simulator using C-band RADARSAT-2 quad-polarized synthetic aperture radar (SAR) images. Our results show that the two new RCM CP models, CoVe-Pol and CoHo-POL, can provide efficient methodologies for wind retrieval.

There are interactions between surface waves and currents, the latter includes wind-driven current and tidal current. Currents influence surface waves though advection transport and shear instability generation processes. While the horizontal gradient of current is commonly considered to calculate wave-current interaction source term in most wave models, the vertical gradient of current (current shear) has been simplified. In coastal waters, strong background currents with topographic fluctuations at the scale of surface waves have a resonance effect on surface waves. However, this resonance process is currently ignored in existing wave models. To evaluate the effects of current shear and topographic fluctuations on surface waves more accurately, an analytical model is proposed to describe the modification of the amplitude of orbital velocities for surface waves. The amplitude of orbital velocities exhibits significant variations when considering both current shear and topographic fluctuation effects. Wave particle trajectory equations that incorporate current shear and topographic fluctuations are derived based on this analytical model. In deep waters, current shear can increase or decrease the horizontal radius of wave particle trajectory by approximately 0.3m, while the modification of horizontal amplitude of orbital velocities is about 0.3m/s. In shallow waters, with both topographic fluctuations and background current present, both horizontal and vertical radii of wave particle trajectory change by approximately ±0.1m respectively, and the modification of both horizontal and vertical amplitudes of orbital velocities is about 0.2-0.3m/s. Moreover, in some cases, there are reversals in the direction of wave particle trajectories. [ABSTRACT FROM AUTHOR]

The mannose operon of Bacillus subtilis consists of three genes, manP, manA, and yjdF, which are responsible for the transport and utilization of mannose. Upstream and in the same orientation as the mannose operon a regulatory gene, manR, codes for a transcription activator of the mannose operon, as shown in this study. Both mannose operon transcription and manR transcription are inducible by mannose. The presence of mannose resulted in a 4- to 7-fold increase in expression of lacZ from the manP promoter (PmanP) and in a 3-fold increase in expression of lacZ from the manR promoter (PmanR). The transcription start sites of manPA-yjdF and manR were determined to be a single A residue and a single G residue, respectively, preceded by -10 and -35 boxes resembling a vegetative {sigma}A promoter structure. Through deletion analysis the target sequences of ManR upstream of PmanP and PmanR were identified between bp -80 and -35 with respect to the transcriptional start site of both promoters. Deletion of manP (mannose transporter) resulted in constitutive expression from both the PmanP and PmanR promoters, indicating that the phosphotransferase system (PTS) component EIIMan has a negative effect on regulation of the mannose operon and manR. Moreover, both PmanP and PmanR are subject to carbon catabolite repression (CCR). By constructing protein sequence alignments a DNA binding motif at the N-terminal end, two PTS regulation domains (PRDs), and an EIIA- and EIIB-like domain were identified in the ManR sequence, indicating that ManR is a PRD-containing transcription activator. Like findings for other PRD regulators, the phosphoenolpyruvate (PEP)-dependent phosphorylation by the histidine protein HPr via His15 plays an essential role in transcriptional activation of PmanP and PmanR. Phosphorylation of Ser46 of HPr or of the homologous Crh protein by HPr kinase and formation of a repressor complex with CcpA are parts of the B. subtilis CCR system. Only in the double mutant with an HPr Ser46Ala mutation and a crh knockout mutation was CCR strongly reduced. In contrast, PmanR and PmanP were not inducible in a ccpA deletion mutant. [ABSTRACT FROM AUTHOR]

Background: A capable expression vector is mainly characterized by its production efficiency, stability and induction response. These features can be influenced by a variation of modifications and versatile genetic modules. Results: We examined miscellaneous variations of a rhaPBAD expression vector. The introduction of a stem loop into the translation initiation region of the rhaPBAD promoter resulted in the most significant improvement of eGFP expression. Starting from this plasmid, we constructed a set of expression vectors bearing different genetic modules like rop, ccdAB, cer and combinations thereof, and tested the efficiency of expression and plasmid stability. The plasmid pWA21, containing the stem loop, one cer site and rop, attained high expression levels accompanied by a good stability, and on that score seems to be a well-balanced choice. Conclusion: We report the generation of variations of the rhaPBAD expression vector and characterization hereof. The genetic modules showed a complex interplay, therefore two positive effects combined sometimes resulted in a disadvantage. [ABSTRACT FROM AUTHOR]