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Fargesia, the largest genus within the temperate bamboo tribe Arundinarieae, has more than 90 species mainly distributed in the mountains of Southwest China. The Fargesia bamboos are important components of the subalpine forest ecosystems that provide food and habitat for many endangered animals, including the giant panda. However, species-level identification of Fargesia is difficult. Moreover, the rapid radiation and slow molecular evolutionary rate of Fargesia pose a significant challenge to using DNA barcoding with standard plant barcodes (rbcL, matK, and ITS) in bamboos. With progress in the sequencing technologies, complete plastid genomes (plastomes) and nuclear ribosomal DNA (nrDNA) sequences have been proposed as organelle barcodes for species identification; however, these have not been tested in bamboos. We collected 196 individuals representing 62 species of Fargesia to comprehensively evaluate the discriminatory power of plastomes and nrDNA sequences compared to standard barcodes. Our analysis indicates that complete plastomes have substantially higher discriminatory power (28.6%) than standard barcodes (5.7%), whereas nrDNA sequences show a moderate improvement (65.4%) compared to ITS (47.2%). We also found that nuclear markers performed better than plastid markers, and ITS alone had higher discriminatory power than complete plastomes. The study also demonstrated that plastomes and nrDNA sequences can contribute to intrageneric phylogenetic resolution in Fargesia. However, neither of these sequences were able to discriminate all the sampled species, and therefore, more nuclear markers need to be identified.

It is urgent to develop highly efficient, stable and low-cost bifunctional electrocatalysts for overall water splitting. Herein, an iron-nickel phosphide (Fe2P/Ni2P) heterostructure, constructed by Fe2P nanoparticles embedded on Ni2P nanosheets, is strategically fabricated on nickel foam via a facile process. As a bifunctional electrocatalyst, the Fe2P/Ni2P heterostructure delivers a very low overpotential of 64 mV (or 185 mV) to reach current density of 10 mA cm−2 for hydrogen (or oxygen) evolution reaction. When simultaneously employed as both the anode and cathode electrodes, it demonstrates an ultralow cell voltage of 1.49 V@10 mA cm−2 for full water splitting with nearly 100% Faradaic efficiency, and superior long-term stability even over 100 h. Density functional theory calculations manifest that a strong heterointerface interaction could cause electron redistribution near the Fe2P/Ni2P heterointerface and optimize the ΔGH* of P sites, thus enhancing catalytic activity. Additionally, the 3D porous heterostructure is benefit to expose rich active sites and facilitate ion diffusion and gas bubble release, thus promoting the catalytic performance. This work opens up a new strategical approach for rational design of metal phosphide-based heterostructures as highly efficient and stable bifunctional electrocatalysts for water splitting.

All-solid-state lithium metal batteries (ASSLMBs) show great potential for high energy density as well as enhanced safety. However, the practical application is still hampered by uncontrollable dendrite growth and limited cycling stability. Herein, a stable Li3N-LiF-enriched interface is in-situ induced between poly (ethylene oxide) (PEO)-based solid electrolyte and Li anode by introducing lithium nitrate (LiNO3). Combining surface characterizations and molecular dynamics simulations, firstly, it reveals that the addition of LiNO3 facilitates the decomposition of lithium bis(trifluoromethylsulfonyl) imide (LiTFSI) to preferentially form LiF. The Li3N-LiF-enriched interface greatly improves interface contact between solid electrolyte and Li anode, leading to homogenous Li deposition. With LiNO3 addition, the critical current density of PEO-based electrolyte can be enhanced to high value of > 0.9 mA cm–2. Meanwhile, all-solid-state LMBs coupled with LiFePO4 cathode show superior cycling stability and Coulombic efficiency (CE), especially, the initial CE is up to 94.12 % at 0.5 C. Even paired with high-potential NCM cathode, promoted electrochemical performances can be achieved, with 91.4 % capacity retention after 200 cycles at 0.3 C. What's more, this work illustrates the importance of interface modification in ASSLMBs from the perspective of the relationship between impedances and overpotentials.

Matrix Factorization (MF) is a widely used collaborative filtering technique for effectively modeling a user-item interaction in recommender system. Despite the successful application of MF and its variants, the method proves to be effective only in situations where there is an abundance of user-item interactions. However, user-item interaction data are usually sparse, limiting the effectiveness of the method. In addressing this problem, recent methods have proposed to use knowledge graphs (KGs) as additional information to complement the sparse user-item interaction data. This has proved challenging given the complexity of the KG structure. In this paper, we propose a collaborative filtering method that takes advantage of knowledge graphs. More specifically, the embedding of a user and item are both grounded on the item’s attributes in the knowledge graph, and are aggregated with generic user and item representations modeled by MF for implicit recommendation. Our model has demonstrated to outperform the recent state-of-the-art method KGCN [18] in very sparse settings, showing an effective integration of KGs in recommender systems.

The shuttle effect of lithium polysulfides (LiPSs) and sluggish redox conversion significantly hinder practical implementation of lithium-sulfur batteries (LSBs). To overcome these issues, herein, we present MoP quantum dots anchored N, P-doped graphene (MPQ@G) as a multifunctional LSB cathode. The N, P-doped graphene layers serve as a conductive skeleton to support the MoP QDs which can accelerate the electron transfer, physically hinder the polysulfide migration and thus enhance the electrochemical performance. More importantly, as a polar and conductive catalyst, MoP QDs provide catalytically active sites for the conversion of LiPSs. As a result, the LSBs with MPQ@G/S cathodes deliver an elevated initial capacity of 1220.2 mAh g−1 at 0.2 C and remain 98.9% after rate cycles, signifying its exceptional cycling stability. Moreover, it displays a large capacity of 681.2 mAh g−1 even at a high rate of 1 C. The Li-S pouch cell also presents high specific capacities and preeminent cycling stabilities, confirming its great potential for high-rate applications. Density functional theory calculations demonstrate the improved absorptivity and redox conversion reversibility of LiPSs. This work provides an efficient strategy to improve composite with highly adsorptive and catalytic properties for high-performance Li-S batteries.

Oxygen evolution reaction (OER) is a rate-limiting step in electrocatalytic water splitting due to its sluggish reaction kinetics. Therefore, it is still challengeable to develop an inexpensive and efficient OER catalyst via a facile and scalable synthesis method. To address such issues, herein, we present a facile and scalable approach to prepare ultrathin NiSe2/FeSe2 heterostructural nanoparticles in-situ grown on NiFe foam (NFS/NFF), which can be employed as a self-supported non-noble metal-based catalyst for OER. The NFS/NFF catalyst delivers outstanding OER performance with a small Tafel slope of 57.07 mV dec−1 and a low overpotential of 274 mV at 40 mA cm−2 and displays terrific long-term stability, surpassing the performance of commercial RuO2 and single component NiSe2/NF catalyst. The results of XPS manifest that there is a strong heterointerface interaction between NiSe2 and FeSe2. In addition, combined with density functional theory (DFT) calculations, we further confirmed that the synergistic interface effect between NiSe2 and FeSe2 reduces the value of the Gibbs free energy of oxygen-containing intermediates as determining step (RDS) from 3.15 eV (NiSe2) to 2.41 eV (NiSe2/FeSe2 heterostructures), leading to excellent OER performance. This work provides a novel strategy to rationally design and fabricate selenide-based heterostructural nanoparticles via a facile method, which can extend to prepare other non-precious OER catalysts with high efficiency and long-term stability.

Different clinicopathologic characteristics could contribute to inconsistent prognoses of small breast neoplasms (T1a/T1b). This study was done to conduct a retrospective analysis and establish a clinical prediction model to predict individual survival outcomes of patients with small carcinomas of the breast.Based on the Surveillance, Epidemiology, and End Results (SEER) database, eligible patients with small breast carcinomas were analyzed. Univariate analysis and multivariate analysis were performed to clarify the indicators of overall survival. Pooling risk factors enabled nomograms to be constructed and further predicted 3-year, 5-year, and 10-year survival of patients with small breast cancer. The model was internally validated for discrimination and calibration.A total of 17,543 patients with small breast neoplasms diagnosed between 2013 and 2016 were enrolled. Histologic grade, lymph node stage, estrogen receptor or progesterone receptor status, and molecular subtypes of breast cancer were regarded as the risk factors of prognosis in a Cox proportional hazards model (P .05). A nomogram was constructed to give predictive accuracy toward individual survival rate of patients with small breast neoplasms.This prognostic model provided a robust and effective method to predict the prognosis of patients with small breast cancer.

Determining atomic structure of intercalated metallic layer under graphene is a hot-topic due to the potential applications in electronic engineering. In this study, Pb-intercalated graphene (PbG) is fabricated on SiC substrate and the atomic structure and electronic properties of the intercalated Pb atoms underneath graphene are investigated by scanning tunneling microscopy/spectroscopy (STM/STS). As the crystal facet of intercalated Pb atoms can be arranged in (111) (unit cell, 0.35 nm × 0.35 nm) and (110) (unit cell, 0.61 nm × 0.35 nm), mottled moire pattern (period, 2.5 nm) and striated moire pattern (period, 2.1 nm) are formed. Atomic arrangement of the intercalated Pb is sensitive to tip scanning resulting in the conversion of the two moire patterns. Nevertheless, the crystal orientation of moire patterns is always aligned with zigzag direction of graphene. As revealed by STS, PbG performs the similar electronic states to those of free-standing graphene due to the shielding effects of Pb intercalation. The crystallographic relationship between graphene and Pb atoms is also confirmed by density functional theory (DFT) calculations. The study provides crucial for understanding the structure of intercalated Pb atoms underneath a graphene layer, which may enable the development of new 2D materials capped by graphene.

It is difficult to define patients with primary trastuzumab resistance (PTR) after (neo)adjuvant trastuzumab with minimal data and understanding of the actual prevalence, prognosis, and potential treatment strategies in the real-world setting.The medical records of 1096 patients with human epidermal growth factor receptor 2-positive early-stage breast cancer who had received (neo)adjuvant trastuzumab-containing treatment from 2010 to 2016 in the Cancer Hospital and Chinese Academy of Medical Sciences were reviewed. PTR was defined as recurrence during adjuvant trastuzumab or within 12 months from their last (neo)adjuvant trastuzumab dosage. The cutoff date for data collection was September 1, 2018, with a median follow-up time of 46 months.A total of 126 recurrences were observed, and 75 (6.8%; 75/1096) of them were categorized as PTR; the remaining were non-PTR. The prognosis of patients in the PTR group was much inferior to those in the non-PTR group (27 months vs. not reached; P .01). As expected, patients with PTR did possess a much lower response rate to first-line trastuzumab-containing therapy (27.3% vs. 61.9%; P = .02). Subgroup analyses indicated that patients in the PTR group seemed to get little survival benefit from the reuse of trastuzumab compared with those without trastuzumab (26 months vs. 28 months; P = .80). However, in the non-PTR group, re-treatment with trastuzumab in the metastatic setting prolonged the survival of patients compared to those without trastuzumab (not reached vs. 34 months; P = .04).This study verified the rationality of present definition of PTR after (neo)adjuvant trastuzumab. Patients with PTR did have a poor prognosis. Further research and clinical trials are required to establish the best treatment patterns for these patients.

With an aging population, late-life depression has been a major health problem in rural China. This study aims to explore the gender-specific prevalence of geriatric depression in rural Tianjin, its influencing factors, and to provide a scientific basis for the prevention and intervention of depression in the elderly.A cross-sectional study of 4,933 elderly individuals in rural Tianjin was conducted using the cluster sampling method. The independent samples t-test and chi-squared test were used to assess differences in participants' characteristics by depressive symptoms, while multiple linear regressions and multiple logistic regressions were used to analyze the potential influencing factors of depression.The prevalence of geriatric depression was found to be 12.2% in the study participants (9.5% in men and 14.5% in women). Gender, education, household income, employment, living alone, social activities, physical exercise and chronic diseases were associated with depression (P0.05). In addition to the above factors, sleep duration was also related with scores on self-rating depression scale (P0.05).The study used a cross-sectional approach, so causation cannot be concluded.Late-life depression is a serious mental health issue in rural China, highlighting the importance of appropriate diagnosis and treatment as a priority to improve the quality of mental health.

Objective To develop an UPLC-MS/MS method for the accurate quantification of Estriol (E3), a new radioprotective agent, and observe the variation in pharmacokinetic characteristics of E3 after irradiation. As a hormone drug, the gender differences of E3 metabolism were also concerned here. Methods Various chromatographic and mass spectrometric conditions of E3 were optimized. The specificity, linearity, precision and accuracy of UPLC-MS/MS method were validated. Twenty SD rats, half male and half female, were administered with intramuscular (im) injection of 2.7 ​mg/kg E3, and then divided randomly into two groups, sham-irradiated group (Con) and irradiated group (IR). IR group was irradiated to 7 ​Gy of γ-rays. Blood samples were collected at different times post-irradiation and E3 concentrations were detected. The changes of concentration-time variation and pharmacokinetic parameters for E3 after irradiation were investigated, together with metabolic differences between male and female rats. Results The range of the calibration curve of UPLC-MS/MS for E3 was 1.00–200.0 ​ng/mL. Con group reached maximum concentration (Cmax) (77.57 ​± ​18.71) ng/mL at (0.68 ​± ​0.29) h (Tmax) after im injection. The drug concentration-time profiles and pharmacokinetic parameters of E3 were consistent before and after irradiation. The areas under time curve (AUC0-t) of E3 were (353 ​± ​74) h·ng/mL for Con group, and (299 ​± ​74) h·ng/mL for IR group (P ​> ​0.05). There were also no statistical differences in pharmacokinetic parameters between female and male rats. The elimination half-lifes (T1/2) of males and females were (3.02 ​± ​0.68) h and (3.01 ​± ​0.42) h in Con group, and (3.64 ​± ​0.51) h and (3.38 ​± ​0.60) h in IR group, respectively (P ​> ​0.05). Conclusion A rapid and sensitive UPLC-MS/MS method for determination of E3 was established. The pharmacokinetic characteristics of E3 in rat were not affected by 7 ​Gy irradiation and gender differences. This study provided a theoretical basis for the development and application of new radiation injury treatment drug.

Summary Background Despite therapeutic advances in HER2-positive metastatic breast cancer, resistance to trastuzumab inevitably develops. In the PHOEBE study, we aimed to assess the efficacy and safety of pyrotinib (an irreversible pan-HER inhibitor) plus capecitabine after previous trastuzumab. Methods This is an open-label, randomised, controlled, phase 3 trial done at 29 hospitals in China. Patients with pathologically confirmed HER2-positive metastatic breast cancer, aged 18–70 years, who had an Eastern Cooperative Oncology Group performance status of 0 or 1, and had been previously treated with trastuzumab and taxanes were randomly assigned (1:1) to receive oral pyrotinib 400 mg or lapatinib 1250 mg once daily plus oral capecitabine 1000 mg/m2 twice daily on days 1–14 of each 21-day cycle. Randomisation was done via a centralised interactive web-response system with a block size of four or six and stratified by hormone receptor status and previous lines of chemotherapy for metastatic disease. The primary endpoint was progression-free survival according to masked independent central review. Efficacy and safety were assessed in all patients who received at least one dose of the study drugs. Results presented here are from a prespecified interim analysis. This study is registered with ClinicalTrials.gov, NCT03080805. Findings Between July 31, 2017, and Oct 30, 2018, 267 patients were enrolled and randomly assigned. 134 patients received pyrotinib plus capecitabine and 132 received lapatinib plus capecitabine. At data cutoff of the interim analysis on March 31, 2019, median progression-free survival was significantly longer with pyrotinib plus capecitabine (12·5 months [95% CI 9·7–not reached]) than with lapatinib plus capecitabine (6·8 months [5·4–8·1]; hazard ratio 0·39 [95% CI 0·27–0·56]; one-sided p Interpretation Pyrotinib plus capecitabine significantly improved progression-free survival compared with that for lapatinib plus capecitabine, with manageable toxicity, and can be considered an alternative treatment option for patients with HER2-positive metastatic breast cancer after trastuzumab and chemotherapy. Funding Jiangsu Hengrui Medicine and National Key R&D Program of China. Translations For the Chinese translation of the abstract see Supplementary Materials section.

Background Alhtough anti-HER2 tyrosine kinase inhibitors (TKIs) have radically prolonged survival and improved prognosis in HER2-positive breast cancer patients, resistance to these therapies is a constant obstacle leading to TKIs treatment failure and tumour progression. Methods To develop new strategies to enhance TKIs efficiency by combining synergistic gene targets, we performed panel library screening using the CRISPR/Cas9 knockout technique based on data mining across TCGA data sets and verified the candidate target in preclinical models and breast cancer high-throughput sequencing data sets. Results We identified that CDK12, co-amplified with HER2 in a high frequency, is powerful to sensitise or resensitise HER2-positive breast cancer to anti-HER2 TKIs lapatinib, evidenced by patient-derived organoids in vitro and cell-derived xenograft or patient-derived xenograft in vivo. Exploring mechanisms, we found that inhibition of CDK12 attenuated PI3K/AKT signal, which usually serves as an oncogenic driver and is reactivated when HER2-positive breast cancers develop resistance to lapatinib. Combining CDK12 inhibition exerted additional suppression on p-AKT activation induced by anti-HER2 TKIs lapatinib treatment. Clinically, via DNA sequencing data for tumour tissue and peripheral blood ctDNA, we found that HER2-positive breast cancer patients with CDK12 amplification responded more insensitively to anti-HER2 treatment than those without accompanying CDK12 amplification by harbouring a markedly shortened progression-free survival (PFS) (median PFS: 4.3 months versus 6.9 months; hazards ratio [HR] = 2.26 [95% confidence interval [CI] = 1.32–3.86]; P = 0.0028). Conclusions Dual inhibition of HER2/CDK12 will prominently benefit the outcomes of patients with HER2-positive breast cancer by sensitising or resensitising the tumours to anti-HER2 TKIs treatment.