Multigene phylogeny and morphology reveal three new species of Cytospora isolated from diseased plant branches in Fengtai District, Beijing, China

Members of Cytospora include saprobes, endophytes and important plant pathogens, which are widely distributed on various wood hosts and have a wide global distribution. In this study, the species definitions were conducted, based on multigene phylogeny (ITS, act, rpb2, tef1-α and tub2 genes) and comparisons of morphological characters. A total of 22 representative isolates obtained from 21 specimens in Fengtai District of Beijing City were identified as seven species of Cytospora, including four known species (C. albodisca, C. ailanthicola, C. euonymina, C. haidianensis) and three novel species (C. fengtaiensis, C. pinea, C. sorbariae). The results provide an understanding of the taxonomy of Cytospora species associated with canker and dieback diseases in Fengtai District, Beijing, China

Elucidating the susceptibility to breast cancer: an in-depth proteomic and transcriptomic investigation into novel potential plasma protein biomarkers

Objectives: This study aimed to identify plasma proteins that are associated with and causative of breast cancer through Proteome and Transcriptome-wide association studies combining Mendelian Randomization.Methods: Utilizing high-throughput datasets, we designed a two-phase analytical framework aimed at identifying novel plasma proteins that are both associated with and causative of breast cancer. Initially, we conducted Proteome/Transcriptome-wide association studies (P/TWAS) to identify plasma proteins with significant associations. Subsequently, Mendelian Randomization was employed to ascertain the causation. The validity and robustness of our findings were further reinforced through external validation and various sensitivity analyses, including Bayesian colocalization, Steiger filtering, heterogeneity and pleiotropy. Additionally, we performed functional enrichment analysis of the identified proteins to better understand their roles in breast cancer and to assess their potential as druggable targets.Results: We identified 5 plasma proteins demonstrating strong associations and causative links with breast cancer. Specifically, PEX14 (OR = 1.201, p = 0.016) and CTSF (OR = 1.114, p < 0.001) both displayed positive and causal association with breast cancer. In contrast, SNUPN (OR = 0.905, p < 0.001), CSK (OR = 0.962, p = 0.038), and PARK7 (OR = 0.954, p < 0.001) were negatively associated with the disease. For the ER-positive subtype, 3 plasma proteins were identified, with CSK and CTSF exhibiting consistent trends, while GDI2 (OR = 0.920, p < 0.001) was distinct to this subtype. In ER-negative subtype, PEX14 (OR = 1.645, p < 0.001) stood out as the sole protein, even showing a stronger causal effect compared to breast cancer. These associations were robustly supported by colocalization and sensitivity analyses.Conclusion: Integrating multiple data dimensions, our study successfully pinpointed plasma proteins significantly associated with and causative of breast cancer, offering valuable insights for future research and potential new biomarkers and therapeutic targets

A phase 1 dose-escalation study of the poly(ADP-ribose) polymerase inhibitor senaparib in Australian patients with advanced solid tumors

Background: Senaparib is a novel, selective poly(ADP-ribose) polymerase-1/2 inhibitor with strong antitumor activity in preclinical studies. This first-in-human, phase 1, dose-escalation study examined the safety and preliminary efficacy of senaparib in patients with advanced solid tumors. Methods: Patients with advanced solid tumors were enrolled from three centers in Australia, using a conventional 3 + 3 design. Dose-escalation cohorts continued until the maximum tolerated dose or a recommended phase 2 dose was determined. Patients received one dose of oral senaparib and, if no dose-limiting toxicity occurred within 7 days, they received senaparib once daily in 3-week cycles. The primary end points were safety and tolerability. Results: Thirty-nine patients were enrolled at 10 dose levels ranging from 2 to 150 mg. No dose-limiting toxicities were observed in any cohort. Most treatment-emergent adverse events were grade 1–2 (91%). Seven patients (17.9%) reported hematologic treatment-emergent adverse events. Treatment-related adverse events occurred in eight patients (20.5%), and the most frequent was nausea (7.7%). Two deaths were reported after the end of study treatment, one of which was considered a complication from senaparib-related bone marrow failure. Pharmacokinetic analysis indicated that senaparib the accumulation index was 1.06–1.67, and absorption saturation was 80–150 mg daily. In 22 patients with evaluable disease, the overall response rate was 13.6%, and the disease control rate was 81.8%. The overall response rate was 33.3% for the BRCA mutation-positive subgroup and 6.3% for the nonmutated subgroup. Conclusions: Senaparib was well tolerated in Australian patients with advanced solid tumors, with encouraging signals of antitumor activity. The recommended phase 2 dose for senaparib was determined to be 100 mg daily. ClinicalTrials.gov ID: NCT03507543

Modelling on Shock-Induced Energy Release Behavior of Reactive Materials considering Mechanical-Thermal-Chemical Coupled Effect

Reactive material (RM) is a new type of energetic material, which is widely used in the military technology fields such as fragmentation warheads and shaped charge warheads. Violent chemical reactions take place in the impact process of reactive materials, and how to realize the macro numerical simulation of shock-induced energy release behavior of reactive materials is one of the most urgent problems to be solved for its future military applications. In this study, a numerical simulation approach and procedure is proposed, which can simulate the shock-induced energy release behavior of reactive materials on a macro scale. Firstly, program implementation of the mechanical-thermal-chemical coupled effect model for RM is realized in the second-development interface of LS-DYNA software. Then, the adaptive simulated annealing algorithm is used to fit the chemical reaction kinetic parameters of RM using the direct ballistics test data. Finally, the simulation calculation of the fragment penetrating upon steel plate is carried out to expand the applicability of the numerical simulation approach proposed in this study. The results show that the numerical simulation approach proposed in this study can reproduce the results of the direct ballistics test more accurately, which assumes practical significance for the engineering application of reactive materials in the military field in the future

Health Evaluation and Risk Factor Identification of Urban Lakes—A Case Study of Lianshi Lake

Health assessment and risk factor identification represent the premise and foundation of scientific management and ecological restoration of urban lakes. Based on in-depth understanding of the nature–society duality of urban lakes, a framework for evaluating urban lake health was constructed, including four modules, namely, establishing an index system; determining the index weight; identifying risk factors; and a comprehensive lake health evaluation. Employing this framework, we evaluated Lianshi Lake, Beijing, classifying the lake condition as “sub-healthy”. Based on the evaluation data, we identified the health risk factors of the lake. We applied standard difference rate (SDR) and risk degree (Rd) (safe degree (Sd)) concepts, and classified the indices of risk areas employing the Pareto analysis method. Finally, we identified the lake residence period, landscape connectivity, and eutrophication as the major risk factors in Lianshi Lake. Three factors constitute the basis of ecosystem health and are key targets of ecological restoration: the lake residence period represents the hydrological and hydrodynamic characteristics of the lake; landscape connectivity is described from an ecological perspective, and represents the integrity of the lake ecosystem; and the eutrophication states describe the water quality characteristics and represent the availability of lake water. The results contribute to decision-making for comprehensive urban lake management

DataSheet1_Elucidating the susceptibility to breast cancer: an in-depth proteomic and transcriptomic investigation into novel potential plasma protein biomarkers.zip

Objectives: This study aimed to identify plasma proteins that are associated with and causative of breast cancer through Proteome and Transcriptome-wide association studies combining Mendelian Randomization.Methods: Utilizing high-throughput datasets, we designed a two-phase analytical framework aimed at identifying novel plasma proteins that are both associated with and causative of breast cancer. Initially, we conducted Proteome/Transcriptome-wide association studies (P/TWAS) to identify plasma proteins with significant associations. Subsequently, Mendelian Randomization was employed to ascertain the causation. The validity and robustness of our findings were further reinforced through external validation and various sensitivity analyses, including Bayesian colocalization, Steiger filtering, heterogeneity and pleiotropy. Additionally, we performed functional enrichment analysis of the identified proteins to better understand their roles in breast cancer and to assess their potential as druggable targets.Results: We identified 5 plasma proteins demonstrating strong associations and causative links with breast cancer. Specifically, PEX14 (OR = 1.201, p = 0.016) and CTSF (OR = 1.114, p Conclusion: Integrating multiple data dimensions, our study successfully pinpointed plasma proteins significantly associated with and causative of breast cancer, offering valuable insights for future research and potential new biomarkers and therapeutic targets.</p

MiR-376a and Histone Deacetylation 9 Form A Regulatory Circuitry in Hepatocellular Carcinoma

Background/Aims: Our previous study has demonstrated that down-regulation of miR-376a might contribute to the development of hepatocellular carcinoma (HCC), but the mechanism underlying this down-regulation remains obscure. Methods/Results: histone deacetylase (HDAC) inhibitor increased the level of miR-376a in L02 and Huh7 cells by up-regulating the acetylation level of histone 3 at the Maternally expressed 3 (Meg3) differentially methylated region (DMR). Interestingly, HDAC9, a histone deacetylase responsible for deacetylating lysine 18 of histone 3 (H3K18), was identified as the target of miR-376a. In addition, HDAC9 siRNA increased the expression of miR-376a by up-regulating the global histone H3K18 acetylation level, with Meg3 DMR included. Finally, miR-376a and HDAC9 were inversely correlated in HCC. Conclusion: HDAC9 plays an important role both as effects and targets of miR-376a

Two-Directional Tuning of Distributed Feedback Film Dye Laser Devices

We demonstrate a two-directional tuning method of distributed feedback (DFB) film dye laser devices to achieve high quality lasing and a large tuning range. In this work, we proposed a simple method to fabricate a continuous tunable solid-state dye laser on a flexible Polydimethylsiloxane (PDMS) film. In order to obtain stable and tunable output lasing, the stretching property of the gelatine host was improved by mixing with a certain ratio of glycerol to prevent DFB cavity destruction. We employed two different tuning strategies of the DFB film dye lasers, by stretching the PDMS film in two perpendicular directions, and a nearly 40 nm tuning range in each direction was achieved. The laser device maintained single mode lasing with 0.12 nm linewidth during the tuning process. The reported tunable DFB film dye laser devices have huge potential as coherent light sources for sensing and spectroscopy applications