Overexpression of FERONIA receptor kinase MdMRLK2 regulates lignin accumulation and enhances water use efficiency in apple under long-term water deficit condition.

Water use efficiency (WUE) is crucial for apple tree fitness and survival, especially in response to climatic changes. The receptor-like kinase FERONIA is reportedly an essential regulator of plant stress responses, but its role in regulating WUE under water deficit conditions is unclear. Here, we found that overexpressing the apple FERONIA receptor kinase gene, MdMRLK2, enhanced apple WUE under long-term water deficit conditions. Under drought treatment, 35S::MdMRLK2 apple plants exhibited higher photosynthetic capacity and antioxidant enzyme activities than wild-type (WT) plants. 35S::MdMRLK2 apple plants also showed increased biomass accumulation, root activity, and water potential compared to WT plants. Moreover, MdMRLK2 physically interacts with and phosphorylates cinnamoyl-CoA reductase 1, MdCCR1, an enzyme essential for lignin synthesis, at position Ser260. This interaction likely contributed to increased vessel density, vascular cylinder area, and lignin content in 35S::MdMRLK2 apple plants under drought conditions. Therefore, our findings reveal a novel function of MdMRLK2 in regulating apple WUE under water deficit conditions.

Early detection and stratification of colorectal cancer using plasma cell-free DNA fragmentomic profiling.

Timely accurate and cost-efficient detection of colorectal cancer (CRC) is of great clinical importance. This study aims to establish prediction models for detecting CRC using plasma cell-free DNA (cfDNA) fragmentomic features. Whole-genome sequencing (WGS) was performed on cfDNA from 620 participants, including healthy individuals, patients with benign colorectal diseases and CRC patients. Using WGS data, three machine learning methods were compared to build prediction models for the stratification of CRC patients. The optimal model to discriminate CRC patients of all stages from healthy individuals achieved a sensitivity of 92.31% and a specificity of 91.14%, while the model to separate early-stage CRC patients (stage 0-II) from healthy individuals achieved a sensitivity of 88.8% and a specificity of 96.2%. Additionally, the cfDNA fragmentation profiles reflected disease-specific genomic alterations in CRC. Overall, this study suggests that cfDNA fragmentation profiles may potentially become a noninvasive approach for the detection and stratification of CRC.

MdHB7-like positively modulates apple salt tolerance by promoting autophagic activity and Na+ efflux.

Salt stress adversely affects the yield and quality of crops and limits their geographical distribution. Studying the functions and regulatory mechanisms of key genes in the salt stress response is important for breeding crops with enhanced stress resistance. Autophagy plays an important role in modulating the tolerance of plants to various types of abiotic stressors. However, the mechanisms underlying salt-induced autophagy are largely unknown. Cation/Ca2+ exchanger proteins enhance apple salt tolerance by inhibiting Na+ accumulation but the mechanism underlying the response to salt stress remains unclear. Here, we show that the autophagy-related gene MdATG18a modulated apple salt tolerance. Under salt stress, the autophagic activity, proline content, and antioxidant enzyme activities were higher and Na+ accumulation was lower in MdATG18a-overexpressing transgenic plants than in control plants. The use of an autophagy inhibitor during the salt treatment demonstrated that the regulatory function of MdATG18a depended on autophagy. The yeast-one-hybrid assay revealed that the homeodomain-leucine zipper (HD-Zip) transcription factor MdHB7-like directly bound to the MdATG18a promoter. Transcriptional regulation and genetic analyses showed that MdHB7-like enhanced salt-induced autophagic activity by promoting MdATG18a expression. The analysis of Na+ efflux rate in transgenic yeast indicated that MdCCX1 expression significantly promoted Na+ efflux. Promoter binding, transcriptional regulation, and genetic analyses showed that MdHB7-like promoted Na+ efflux and apple salt tolerance by directly promoting MdCCX1 expression, which was independent of the autophagy pathway. Overall, our findings provide insight into the mechanism underlying MdHB7-like-mediated salt tolerance in apple through the MdHB7-like-MdATG18a and MdHB7-like-MdCCX1 modules. These results will aid future studies on the mechanisms underlying stress-induced autophagy and the regulation of stress tolerance in plants.

Fruit crops combating drought: Physiological responses and regulatory pathways.

Drought is a common stress in agricultural production. Thus, it is imperative to understand how fruit crops respond to drought and to develop drought-tolerant varieties. This paper provides an overview of the effects of drought on the vegetative and reproductive growth of fruits. We summarize the empirical studies that have assessed the physiological and molecular mechanisms of the drought response in fruit crops. This review focuses on the roles of calcium (Ca2+) signaling, abscisic acid (ABA), reactive oxygen species signaling, and protein phosphorylation underlying the early drought response in plants. We review the resulting downstream ABA-dependent and ABA-independent transcriptional regulation in fruit crops under drought stress. Moreover, we highlight the positive and negative regulatory mechanisms of microRNAs in the drought response of fruit crops. Lastly, strategies (including breeding and agricultural practices) to improve the drought resistance of fruit crops are outlined.

Identification of novel LRRK2 inhibitors by structure-based virtual screening and alchemical free energy calculation.

The Leucine-rich repeat kinase 2 (LRRK2) target has been identified as a promising drug target for Parkinson's disease (PD) treatment. This study focuses on optimizing the activity of LRRK2 inhibitors using alchemical relative binding free energy (RBFE) calculations. Initially, we assessed various free energy calculation methods across different LRRK2 kinase inhibitor scaffolds. The results indicate that alchemical free energy calculations are promising for prospective predictions on LRRK2 inhibitors, especially for the aminopyrimidine scaffold with an RMSE of 1.15 kcal mol-1 and Rp of 0.83. Following this, we optimized a potent LRRK2 kinase inhibitor identified from previous virtual screenings, featuring a novel scaffold. Guided by RBFE predictions using alchemical methods, this optimization led to the discovery of compound LY2023-001. This compound, with a [1,2,4]triazolo[5,6-b]indole scaffold, exhibited enhanced inhibitory activity against G2019S LRRK2 (IC50 = 12.9 nM). Molecular dynamics (MD) simulations revealed that LY2023-001 formed stable hydrogen bonds with Glu1948, and Ala1950 in the G2019S LRRK2 protein. Additionally, its phenyl substituents engage in strong electrostatic interactions with Lys1906 and van der Waals interactions with Leu1885, Phe1890, Val1893, Ile1933, Met1947, Leu1949, Leu2001, Ala2016, and Asp2017. Our findings underscore the potential of computational methods in the successful optimization of small molecules, offering important insights for the development of novel LRRK2 inhibitors.

MdNAC104 positively regulates apple cold tolerance via CBF-dependent and CBF-independent pathways.

Low temperature is the main environmental factor affecting the yield, quality and geographical distribution of crops, which significantly restricts development of the fruit industry. The NAC (NAM, ATAF1/2 and CUC2) transcription factor (TF) family is involved in regulating plant cold tolerance, but the mechanisms underlying these regulatory processes remain unclear. Here, the NAC TF MdNAC104 played a positive role in modulating apple cold tolerance. Under cold stress, MdNAC104-overexpressing transgenic plants exhibited less ion leakage and lower ROS (reactive oxygen species) accumulation, but higher contents of osmoregulatory substances and activities of antioxidant enzymes. Transcriptional regulation analysis showed that MdNAC104 directly bound to the MdCBF1 and MdCBF3 promoters to promote expression. In addition, based on combined transcriptomic and metabolomic analyses, as well as promoter binding and transcriptional regulation analyses, we found that MdNAC104 stimulated the accumulation of anthocyanin under cold conditions by upregulating the expression of anthocyanin synthesis-related genes, including MdCHS-b, MdCHI-a, MdF3H-a and MdANS-b, and increased the activities of the antioxidant enzymes by promoting the expression of the antioxidant enzyme-encoding genes MdFSD2 and MdPRXR1.1. In conclusion, this study revealed the MdNAC104 regulatory mechanism of cold tolerance in apple via CBF-dependent and CBF-independent pathways.

The ubiquitin-binding protein MdRAD23D1 mediates drought response by regulating degradation of the proline-rich protein MdPRP6 in apple (Malus domestica).

RAD23 (RADIATION SENSITIVE23) proteins are a group of UBL-UBA (ubiquitin-like-ubiquitin-associated) proteins that shuttle ubiquitylated proteins to the 26S proteasome for breakdown. Drought stress is a major environmental constraint that limits plant growth and production, but whether RAD23 proteins are involved in this process is unclear. Here, we demonstrated that a shuttle protein, MdRAD23D1, mediated drought response in apple plants (Malus domestica). MdRAD23D1 levels increased under drought stress, and its suppression resulted in decreased stress tolerance in apple plants. Through in vitro and in vivo assays, we demonstrated that MdRAD23D1 interacted with a proline-rich protein MdPRP6, resulting in the degradation of MdPRP6 by the 26S proteasome. And MdRAD23D1 accelerated the degradation of MdPRP6 under drought stress. Suppression of MdPRP6 resulted in enhanced drought tolerance in apple plants, mainly because the free proline accumulation is changed. And the free proline is also involved in MdRAD23D1-mediated drought response. Taken together, these findings demonstrated that MdRAD23D1 and MdPRP6 oppositely regulated drought response. MdRAD23D1 levels increased under drought, accelerating the degradation of MdPRP6. MdPRP6 negatively regulated drought response, probably by regulating proline accumulation. Thus, "MdRAD23D1-MdPRP6" conferred drought stress tolerance in apple plants.

Identification of CBPA as a New Inhibitor of PD-1/PD-L1 Interaction.

Targeting of the PD-1/PD-L1 immunologic checkpoint is believed to have provided a real breakthrough in the field of cancer therapy in recent years. Due to the intrinsic limitations of antibodies, the discovery of small-molecule inhibitors blocking PD-1/PD-L1 interaction has gradually opened valuable new avenues in the past decades. In an effort to discover new PD-L1 small molecular inhibitors, we carried out a structure-based virtual screening strategy to rapidly identify the candidate compounds. Ultimately, CBPA was identified as a PD-L1 inhibitor with a KD value at the micromolar level. It exhibited effective PD-1/PD-L1 blocking activity and T-cell-reinvigoration potency in cell-based assays. CBPA could dose-dependently elevate secretion levels of IFN-γ and TNF-α in primary CD4+ T cells in vitro. Notably, CBPA exhibited significant in vivo antitumor efficacy in two different mouse tumor models (a MC38 colon adenocarcinoma model and a melanoma B16F10 tumor model) without the induction of observable liver or renal toxicity. Moreover, analyses of the CBPA-treated mice further showed remarkably increased levels of tumor-infiltrating CD4+ and CD8+ T cells and cytokine secretion in the tumor microenvironment. A molecular docking study suggested that CBPA embedded relatively well into the hydrophobic cleft formed by dimeric PD-L1, occluding the PD-1 interaction surface of PD-L1. This study suggests that CBPA could work as a hit compound for the further design of potent inhibitors targeting the PD-1/PD-L1 pathway in cancer immunotherapy.

Novel Compounds with Promising IDO1 Inhibitory Activity As New Cancer Drug Candidates: Derivatives Of N, N'-diphenylurea Linked With 1,2,3-triazole.

To explore potential indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors, we designed a series of compounds incorporating urea and 1,2,3-triazole structures. IDO1 enzymatic activity experiments with the synthesized compounds were used to verify their molecular-level activity; for instance, the half maximal inhibitory concentration value of compound 3c was 0.07 µM. Our research has yielded a series of novel IDO1 inhibitors which may be beneficial in the development of drugs targeting IDO1 for cancer treatment.

mTORC2-AKT-LAT1 signalling participates in methionine-induced ß-CASEIN expression in mammary epithelial cells of dairy cows.

This study investigated the role of the mammalian target of rapamycin complex 2 (mTORC2)-protein kinase B (AKT) signalling in methionine (Met)-induced L-type amino acid transporter 1 (LAT1) expression and milk protein production. Primary mammary epithelial cells (MECs) from mammary parenchymal tissues of three lactating cows and MAC-T bovine MECs were cultured with or without 0.6 mM Met. Rapamycin-insensitive companion of mTOR (RICTOR) siRNA, the mTORC1 inhibitor rapamycin and the AKT activator SC79 were used to evaluate the effects of mTORC2-AKT signalling on Met-induced LAT1 expression and function. Each experiment was performed three times. Data were analysed with a two-sided unpaired t test or ANOVA with the Bonferroni multiple-comparison test. Western blotting showed that Met stimulation increased RICTOR expression (~244.67%; p < 0.05; control, 0.15 ± 0.026; Met, 0.517 ± 0.109) and AKT-S473 levels (~281.42%; p < 0.01; control, 0.253 ± 0.067; Met, 0.965 ± 0.019) in both primary MECs and MAC-T cells. Rapamycin-induced mTORC1 signalling inhibition decreased only Met-induced ß-CASEIN expression by ~21.24% (p < 0.01; Met, 0.777 ± 0.01; Met and rapamycin, 0.612 ± 0.04) and did not affect Met-stimulated AKT-S473 levels, suggesting that mTORC2-AKT activation upon Met stimulation also contributes to milk protein synthesis. LAT1 participates in Met-induced ß-CASEIN expression. In dairy cow MECs, mTORC2 inhibition by RICTOR siRNA decreased LAT1 levels on the plasma membrane by ~45.13% (p < 0.01; control, 0.359 ± 0.006; siRICTOR, 0.197 ± 0.004). However, SC79-induced AKT activation had the opposite effect (p < 0.01). In primary MECs and MAC-T cells, Met stimulation increased cytosolic and plasma membrane LAT1 expression respectively (MECs, 113.98% and 58.43%; MAC-T, 165.85% and 396.39%; p < 0.05). However, RICTOR siRNA significantly reduced Met-induced plasma membrane LAT1 expression (~76.48%; Met, 0.539 ± 0.05; Met and siRICTOR, 0.127 ± 0.012; p < 0.05). Thus, Met increased LAT1 expression and function via mTORC2-AKT signalling, upregulating milk protein synthesis in dairy cow MECs.

Thermodynamic integration combined with molecular dynamic simulations to explore the cross-resistance mechanism of isoniazid and ethionamide.

Tuberculosis is an ancient disease of mankind, and its causative bacterium is Mycobacterium tuberculosis. Isoniazid is one of the most effective first-line antituberculosis drugs. As prodrugs, it and its derivative ethionamide act on enoyl-acyl carrier protein reductase (InhA) after being oxidized in bacteria, and kill the bacteria by inhibiting the formation of M. tuberculosis cell walls. However, the S94A mutation of InhA causes M. tuberculosis to develop cross-resistance to isoniazid and ethionamide. This work is dedicated to studying the cross-resistance mechanism of isoniazid and ethionamide through theoretical calculations. First, thermodynamic integral simulations are used to accurately calculate the relative binding energy of two drugs in the mutant and wild-type system. Furthermore, through classic molecular dynamic simulations and molecular mechanics generalized-Born surface area calculation, some key residues are identified and the binding affinity of isoniazid and ethionamide reduced by 9-13 kcal/mol due to S94A mutation. The hydrogen bond between Ala94 and isoniazid (ethionamide) disappeared and the energy contribution of Ala94 decreased after the mutation. In addition, the dynamic network analysis indicated that the mutation of Ser94 also indirectly affected the conformation of key residues such as Met147, Thr196, and Leu97, resulting in a reduction in the energy contribution of these residues. Finally, the binding conformation of isoniazid and ethionamide has also undergone major changes. The obtained results could provide valuable information for the future molecular design to overcome the drug resistance.

MdUGT88F1-mediated phloridzin biosynthesis coordinates carbon and nitrogen accumulation in apple.

The high accumulation of phloridzin makes apple (Malus domestica) unique in the plant kingdom, which suggests a vital role of its biosynthesis in physiological processes. In our previous study, silencing MdUGT88F1 (a key UDP-GLUCOSE: PHLORETIN 2'-O-GLUCOSYLTRANSFERASE gene) revealed the importance of phloridzin biosynthesis in apple development and Valsa canker resistance. Here, results from MdUGT88F1-silenced lines showed that phloridzin biosynthesis was indispensable for normal chloroplast development and photosynthetic carbon fixation by maintaining MdGLK1/2 (GOLDEN2-like1/2) expression. Interestingly, increased phloridzin biosynthesis did not affect plant (or chloroplast) development, but reduced nitrogen accumulation, leading to chlorophyll deficiency, light sensitivity, and sugar accumulation in MdUGT88F1-overexpressing apple lines. Further analysis revealed that MdUGT88F1-mediated phloridzin biosynthesis negatively regulated the cytosolic glutamine synthetase1-asparagine synthetase-asparaginase (GS1-AS-ASPG) pathway of ammonium assimilation and limited chlorophyll synthesis in apple shoots. The interference of phloridzin biosynthesis in the GS1-AS-ASPG pathway was also assumed to be associated with its limitation of the carbon skeleton of ammonium assimilation through metabolic competition with the tricarboxylic acid cycle. Taken together, our findings shed light on the role of MdUGT88F1-mediated phloridzin biosynthesis in the coordination between carbon and nitrogen accumulation in apple trees.

A C1q domain-containing protein in Pinctada fucata contributes to the innate immune response and elimination of the pathogen.

The C1q domain-containing proteins (C1qDCs) in bivalve mollusks primarily exist as the globular head C1q proteins (ghC1qs), for the N-terminal collagen domains were very rare in bivalves, although widespread in C1qDCs of vertebrates. In this work, the C1qDC protein with only a ghC1q domain (named as Pf-ghC1q) was identified from Pinctada fucata, and molecular characterization, gene expression, and functional studies were also conducted. The full-length cDNA sequence of Pf-ghC1q was 738 bp long, containing a signal peptide of 23 residues encoded. Pf-ghC1q was clustered with some C1qDCs from other invertebrates in the phylogenetic tree analysis, rather than vertebrates. Pf-ghC1q was detected in all tested tissues, including the mantle, hemocyte, digestive gland, gill, and adductor muscle. Moreover, the expression levels of Pf-ghC1q were up-regulated in all tested tissues after the challenge with Vibrio alginolyticus 4 h later. The expression level of Pf-ghC1q was inhibited by specific si-276, and the low level of Pf-ghC1q affected the phagocytosis efficiency of V. alginolyticus by hemocytes. These results indicated that Pf-ghC1q may participate in the target recognition of V. alginolyticus and the phagocytosis process in the immune response of P. fucata.

PPARγ-AGPAT6 signaling mediates acetate-induced mTORC1 activation and milk fat synthesis in mammary epithelial cells of dairy cows.

This research communication investigated the role and the underlying mechanism of sn-1-acylglycerol-3-phosphate O-acyltransferase 6 (AGPAT6) in acetate-induced mTORC1 signaling activation and milk fat synthesis in dairy cow mammary epithelial cells. The data showed AGPAT6 knockdown significantly decreased acetate-induced phosphorylation of mTORC1 signaling molecules and intracellular triacylglycerol (TAG) content, whereas this inhibition effect was reversed after the addition of 16:0,18:1 phosphatidic acid (PA), suggesting that AGPAT6 could generate PA in response to acetate simulation, that in turn activates mTORC1 signaling. PPARγ is the upstream regulator of AGPAT6 upon acetate stimulation. Luciferase assay with clones containing various deletions and mutation in AGPAT6 promoter showed that there is a RXRα binding sequence located at -96 bp of AGPAT6 promoter. Acetate stimulation significantly increased the interaction between PPARγ and AGPAT6 via this RXRα binding site. Taken together, our data indicated that AGPAT6 could activate mTORC1 signaling by producing PA during acetate-induced milk fat synthesis, and PPARγ acts as a transcription factor to mediate the effect of acetate on AGPAT6 via RXRα.

Genome-Wide Identification of PRP Genes in Apple Genome and the Role of MdPRP6 in Response to Heat Stress.

Plant proline-rich proteins (PRPs) are cell wall proteins that occur in the plant kingdom and are involved in plant development and stress response. In this study, 9 PRP genes were identified from the apple genome and a comprehensive analysis of the PRP family was conducted, including gene structures, phylogenetic analysis, chromosome mapping, and so on. The expression of MdPRPs varied among tissues and in response to different types of stresses. MdPRP4 and MdPRP7 were induced by five detected stress treatments, including heat, drought, abscisic acid, cold, and salt; the expression patterns of the others varied under different types of stress. Subcellular localization showed that MdPRPs mainly functioned in the cytoplasm, except for MdPRP1 and MdPRP5, which also functioned in the nucleus. When MdPRP6 was overexpressed in tobacco, the transgenic plants showed higher tolerance to high temperature (48 °C) compared with wild-type (WT) plants. The transgenic plants showed milder wilting, a lower accumulation of electrolyte leakage, MDA and ROS, and a higher level of chlorophyll and SOD and POD activity, indicating that MdPRP6 may be an important gene in apples for heat stress tolerance. Overall, this study suggested that MdPRPs are critically important for the ability of apple responses to stresses.

Enhanced Autophagic Activity Improved the Root Growth and Nitrogen Utilization Ability of Apple Plants under Nitrogen Starvation.

Autophagy is a conserved degradation pathway for recycling damaged organelles and aberrant proteins, and its important roles in plant adaptation to nutrient starvation have been generally reported. Previous studies found that overexpression of autophagy-related (ATG) gene MdATG10 enhanced the autophagic activity in apple roots and promoted their salt tolerance. The MdATG10 expression was induced by nitrogen depletion condition in both leaves and roots of apple plants. This study aimed to investigate the differences in the growth and physiological status between wild type and MdATG10-overexpressing apple plants in response to nitrogen starvation. A hydroponic system containing different nitrogen levels was used. The study found that the reduction in growth and nitrogen concentrations in different tissues caused by nitrogen starvation was relieved by MdATG10 overexpression. Further studies demonstrated the increased root growth and the higher nitrogen absorption and assimilation ability of transgenic plants. These characteristics contributed to the increased uptake of limited nitrogen nutrients by transgenic plants, which also reduced the starvation damage to the chloroplasts. Therefore, the MdATG10-overexpressing apple plants could maintain higher photosynthetic ability and possess better growth under nitrogen starvation stress.

Overexpression of MdATG8i Enhances Drought Tolerance by Alleviating Oxidative Damage and Promoting Water Uptake in Transgenic Apple.

Water deficit adversely affects apple (Malus domestica) productivity on the Loess Plateau. Autophagy plays a key role in plant responses to unfavorable environmental conditions. Previously, we demonstrated that a core apple autophagy-related protein, MdATG8i, was responsive to various stresses at the transcript level. Here, we investigated the function of this gene in the response of apple to severe drought and found that its overexpression (OE) significantly enhanced drought tolerance. Under drought conditions, MdATG8iOE apple plants exhibited less drought-related damage and maintained higher photosynthetic capacities compared with the wild type (WT). The accumulation of ROS (reactive oxygen species) was lower in OE plants under drought stress and was accompanied by higher activities of antioxidant enzymes. Besides, OE plants accumulated lower amounts of insoluble or oxidized proteins but greater amounts of amino acids and flavonoid under severe drought stress, probably due to their enhanced autophagic activities. Particularly, MdATG8iOE plants showed higher root hydraulic conductivity than WT plants did under drought conditions, indicating the enhanced ability of water uptake. In summary, the overexpression of MdATG8i alleviated oxidative damage, modulated amino acid metabolism and flavonoid synthesis, and improved root water uptake, ultimately contributing to enhanced drought tolerance in apple.

MdUGT88F1-Mediated Phloridzin Biosynthesis Regulates Apple Development and Valsa Canker Resistance.

In apple (Malus domestica), the polyphenol profile is dominated by phloridzin, but its physiological role remains largely elusive. Here, we used MdUGT88F1 (a key UDP-glucose:phloretin 2'-O-glucosyltransferase gene) transgenic apple lines and Malus spp. germplasm to gain more insight into the physiological role of phloridzin in apple. Decreasing phloridzin biosynthesis in apple lines by RNA silencing of MdUGT88F1 led to a series of severe phenotypic changes that included severe stunting, reduced internode length, spindly leaf shape, increased stem numbers, and weak adventitious roots. These changes were associated directly with reduced lignin levels and disorders in cell wall polysaccharides. Moreover, compact organization of tissues and thickened bark enhanced resistance to Valsa canker (caused by the fungus Valsa mali), which was associated with lignin- and cell wall polysaccharide-mediated increases of salicylic acid and reactive oxygen species. Phloridzin was also assumed to be utilized directly as a sugar alternative and a toxin accelerator by V. mali in apple. Therefore, after infection with V. mali, a higher level of phloridzin slightly compromised resistance to Valsa canker in MdUGT88F1-overexpressing apple lines. Taken together, our results shed light on the importance of MdUGT88F1-mediated biosynthesis of phloridzin in the interplay between plant development and pathogen resistance in apple trees.

[Global research hot points on cardiovascular disease--bibliometric analysis based on the ESI hot papers].

With the heavier burden of cardiovascular disease, an abundance of papers emerge every year in the research hotspots, which cover a wide range of types and content. In order to let readers interested in the cardiovascular field quickly understand the research hotspots and research frontier, it is necessary to sort out and summarize the research topic in time. According to the discipline classification, we screened papers in cardiovascular field from the Essential Science Indicators (ESI) hot papers published in 2019. Methods such as bibliometrics, statistical description, hierarchical induction, analysis and interpretation were used a step further to reveal the context and characteristics of research in the field of cardiovascular diseases, summarize the latest progress and development direction in this field, and provide information and hints for the expansion of future research directions. A total of 297 papers were finally included, which were mainly in the field of clinical medicine; The country with the most publications was the United States, while China ranked the fifth in terms of contribution; the research institution with the highest number of published papers was Harvard University; the New England Journal of Medicine (NEJM) has published the most papers, with contribution also from journals such as Circulation, Europe Heart Journal, JAMA, and Lancet. All the papers were categorized into disease burden, disease risk, drug treatment, device treatment and surgical treatment, clinical diagnosis, basic research and others, so as to review and summarize the research front in the field of cardiovascular diseases.

[Global research hotspots on oncology-bibliometric analysis based on the ESI hot papers].

With the increasing global burden of various cancer, an abundance of papers emerged every year in the research hotspots of oncology, covering a wide range of research types and topics. In order to facilitate interested readers to quickly grasp the frontier and hotspots of cancer research, it would be helpful to sort out and summarize the research topic in a timely manner. According to the classification of disciplines, we screened the Essential Science Indicators (ESI) hot papers released in 2019 for the ones in the oncology field, utilized methods such as bibliometrics, statistical description, hierarchical induction, analysis and interpretation to further reveal the context and characteristics of research in the field of oncology, summarized the latest progresses and future directions in the field, and provided information and hints for the trajectory of future research. A total of 549 papers were included, which were mainly from the field of clinical medicine; the country with the most publications was the United States, while China ranked the fourth in terms of contribution; the research institution with the highest number of published papers was University of Texas system; N Engl J Med published the most papers, with contribution also from highly influential journals in the field of oncology such as Lancet Oncol, J Clin Oncol, JAMA Oncol and Cancer Discov. Oncology remained the most popular research topic in the medical research and spanned a wide spectrum of sub-topics. In this study, we demonstrated and sorted out research frontiers in the field of oncology in 12 different research directions including the basic cancer research, cancer epidemiology, and various tumors types related to different systems and organs.