Miracle-dz/UniFAR-FTUs huggingface dataset:
In silico studies of natural product-like caffeine derivatives as potential MAO-B inhibitors/AA2AR antagonists for the treatment of Parkinson's disease

Abstract Parkinson’s disease is considered the second most frequent neurodegenerative disease. It is described by the loss of dopaminergic neurons in the mid-brain. For many decades, L-DOPA has been considered as the gold standard for treating Parkinson’s disease motor symptoms, however, due to the decrease of efficacy, in the long run, there is an urgent need for novel antiparkinsonian drugs. Caffeine derivatives have been reported several times for their neuroprotective properties and dual blockade of monoamine oxidase (MAO) and adenosine A2A receptors (AA2AR). Natural products are currently attracting more focus due to structural diversity and safety in contrast to synthetic drugs. In the present work, computational studies were conducted on natural product-like caffeine derivatives to search for novel potent candidates acting as dual MAO-B inhibitors/AA2AR antagonists for Parkinson’s disease. Our findings revealed two natural products among the top hits: CNP0202316 and CNP0365210 fulfill the requirements of drugs acting on the brain. The selected lead compounds were further studied using molecular dynamics simulation to assess their stability with MAO-B. Current findings might shift the interest towards natural-based compounds and could be exploited to further optimize caffeine derivatives into a successful dual-target-directed drug for managing and halting the neuronal damage in Parkinson’s disease patients.
Reconfigurable weighed microwave photonics filters based on finite impulse response (FIR)

A reconfigurable optical FIR filter based on delay interference structure is proposed, which can realize band-pass and band-stop filtering. The interference structure is mainly composed of an adjustable beam splitter based on Mach-Zehnder interferometer(MZI) structure and a delay line with a phase shifter. Light can be guided to four paths that have different delays and different optical transmission spectrum can be achieved by tuning the amplitude and phase of the four paths by tuning the phase shift of the MZI and delay line. To optimize the transmission spectrum, the theoretical model of the delay interference filter is established and simulated by the transmission matrix method. The simulation results show that the extinction ratio of band-pass filter is greater than 15dB, the extinction ratio of band-stop filter is greater than 40dB, and the in-band fluctuation is lower than 1.5dB.
SS-ESPNet: a lightweight tumor image segmentation model

Medical images are an important tool for doctors to diagnose conditions and treat diseases, and performing accurate medical image segmentation is the basis for disease diagnosis and treatment planning. Currently convolutional neural networks have achieved significant results in the field of medical image segmentation. However, considering the actual usage scenario, the model needs to run on resource-constrained devices, so the model needs to be lightweighted. ESPNet is a lightweight segmentation model structure. The ESP module effectively reduces the number of model parameters and computation, but in this paper, we note that directly reducing the number of model parameters by point-wise convolution will lead to the loss of model feature map information, which in turn leads to the degradation of model performance. In this paper, in order to further reduce the number of model parameters based on the ESPNet model, the number of channels of all model feature maps of the ESPNet model is halved, and in order to mitigate the resulting degradation of model performance, the feature maps of the model are grouped in the channel dimension using the modified Shuffle-ESP module. In order to avoid the loss of information interaction between different grouped convolutional feature maps, the channel information is artificially interacted using a channel shuffle mechanism before entering the atrous convolution of different dilation rate. It is experimentally demonstrated that the model in this paper decreases 54.99% and 54.99% compared to the original model parameters on two tumor data, and that the model performance metrics decrease by 1.59% and 1.76% respectively. The superiority of the proposed model in this paper is demonstrated through experiments.
“Mo” Together or Alone? Investigating the Role of Fundraisers’ Networks in Online Peer-to-Peer Fundraising

In online peer-to-peer fundraising, individual fundraisers, acting on behalf of nonprofit organizations, mobilize their social networks using social media to request donations. Whereas existing studies focus on networks of donors to explain success, we examine the role of the networks of fundraisers and their effect on fundraising outcomes. By drawing on social capital and network theories, we investigate how social capital derived from social media networks and fundraising groups explains individual fundraising success. Using the Movember health campaign on Twitter as an empirical context, we find that fundraising success is associated with a moderate level of centrality in social media networks and moderate group network size. In addition, we find that fundraisers interact only marginally on social media but prefer to connect with each other outside these platforms and engage in group fundraising. Our article contributes to research on fundraising and social networks and provides recommendations for practice.
Expression patterns of the poplar NF-Y gene family in response to Alternaria alternata and hormone treatment and the role of PdbNF-YA11 in disease resistance

Plant nuclear factor-Y (NF-Y) transcription factors (TFs) are key regulators of growth and stress resistance. However, the role of NF-Y TFs in poplar in response to biotic stress is still unclear. In this study, we cloned 26 PdbNF-Y encoding genes in the hybrid poplar P. davidiana × P. bollena, including 12 PdbNF-YAs, six PdbNF-YBs, and eight PdbNF-YCs. Their physical and chemical parameters, conserved domains, and phylogeny were subsequently analyzed. The protein–protein interaction (PPI) network showed that the three PdbNF-Y subunits may interact with NF-Y proteins belonging to two other subfamilies and other TFs. Tissue expression analysis revealed that PdbNF-Ys exhibited three distinct expression patterns in three tissues. Cis-elements related to stress-responsiveness were found in the promoters of PdbNF-Ys, and most PdbNF-Ys were shown to be differentially expressed under Alternaria alternata and hormone treatments. Compared with the PdbNF-YB and PdbNF-YC subfamilies, more PdbNF-YAs were significantly induced under the two treatments. Moreover, loss- and gain-of-function analyses showed that PdbNF-YA11 plays a positive role in poplar resistance to A. alternata. Additionally, RT‒qPCR analyses showed that overexpression and silencing PdbNF-YA11 altered the transcript levels of JA-related genes, including LOX, AOS, AOC, COI, JAZ, ORCA, and MYC, suggesting that PdbNF-YA11-mediated disease resistance is related to activation of the JA pathway. Our findings will contribute to functional analysis of NF-Y genes in woody plants, especially their roles in response to biotic stress.
Overcoming the cardiac toxicities of cancer therapy immune checkpoint inhibitors

Immune checkpoint inhibitors (ICIs) have led recent advances in the field of cancer immunotherapy improving overall survival in multiple malignancies with abysmal prognoses prior to their introduction. The remarkable efficacy of ICIs is however limited by their potential for systemic and organ specific immune-related adverse events (irAEs), most of which present with mild to moderate symptoms that can resolve spontaneously, with discontinuation of therapy or glucocorticoid therapy. Cardiac irAEs however are potentially fatal. The understanding of autoimmune cardiotoxicity remains limited due to its rareness. In this paper, we provide an updated review of the literature on the pathologic mechanisms, diagnosis, and management of autoimmune cardiotoxicity resulting from ICIs and their combinations and provide perspective on potential strategies and ongoing research developments to prevent and mitigate their occurrence.
APPLICATION OF CFD TO THE FLOW COMPUTATION AROUND A MARINE PROPELLER - GRID GENERATION AND INVISCID FLOW COMPUTATION USING EULER EQUATIONS

This paper shows an application of CFD (Computational Fluid Dynamics) to the flow computation around a marine propeller, i.e. grid generation and inviscid flow computation. A new grid generation system around a marine propeller is developed using the Implicit Geometrical Method. The system consists of surface grid and three-dimensional grid generation and it is possible to generate a grid system around a marine propeller with practical configuration. A series of inviscid flow computations are made using Euler equations and continuity equations with pseudo-compressibility. Finite-Volume, cell-centred, 3rd order upwind, and Implicit Approximate Factorisation (IAF) scheme is adopted in order to simulate flow around a propeller at the open test condition with high accuracy and efficiency. Computations are made modifying propeller pitch ratio larger (P=10,5,2) than original value (P=0.95). Computed results are compared with those by the Lifting Surface Method, and good agreement is shown for chordwise load distribution, thrust and torque coefficient. It is also shown that grid skewness may effect the accuracy of the computed results, especially the pressure distribution near the leading edge, when the pitch ratio is small (P=2). A "Multi-block" type grid system, which allows the grid skewness to be kept at a small pitch ratio, is thought to be one of the most probable methods for successful simulation around a marine propeller with a practical configuration.
Differentially expressed genes against Colletotrichum lindemuthiamum in a bean genotype carrying the Co-2 gene revealed by RNA-sequencing analysis

Anthracnose is responsible for large yield losses in common bean crops. RNA-sequencing was used to investigate the differentially expressed genes (DEGs) in response to race 38 of Colletotrichum lindemuthianum in two near-isogenic lines (A25 and A4804) that differ in the presence of a resistance gene located in the cluster Co-2. Their responses were analyzed at different hours after inoculation (0, 24, and 48) and within and between genotypes. In all, 2,850 DEGs were detected, with 2,373 assigned to at least one functional GO term. Enriched GO terms in the resistant genotype were mainly related to functions as a response to stimulus, hormone signaling, cellular component organization, phosphorylation activities, and transcriptional regulation. The region containing the Co-2 cluster was delimited at the end of chromosome Pv11 (46.65–48.65 Mb) through a comparison with the SNP genotypes, obtained using ‘Genotyping by Sequencing,’ among seven resistant lines harboring the Co-2 gene and the susceptible line A25. The delimited region contained 23 DEGs, including 8 typical R genes, that showed higher expression levels in the resistant genotype and non-changes in the susceptible genotype after inoculation. Six R genes encoding protein kinases and an LRR domain formed a cluster in a core region between 46.98 and 47.04 Mb. The alignment of the raw transcriptome reads in the core region revealed structural changes that were used to design four potential breeder-friendly DNA markers, and it revealed some alignments with the intergenic regions, suggesting the presence of genes in addition to those annotated in the reference genome.
WZB117 enhanced the anti-tumor effect of apatinib against melanoma via blocking STAT3/PKM2 axis

Background: Melanoma is the most lethal skin malignant tumor with a short survival once stepping into the metastatic status and poses a therapeutic challenge. Apatinib (a tyrosine kinase inhibitor) is a promising antiangiogenic agent for the treatment of metastatic melanoma. However, antiangiogenic monotherapy is prone to acquired drug resistance and has a limited therapeutic effect. The persistence dependence of glycolytic metabolism in antiangiogenic therapy-resistant cells provides evidence that glycolysis inhibitors may enhance the effect of antiangiogenic therapy. So, this study aimed to investigate whether WZB117 (a specific GLUT1 inhibitor) could enhance the anti-tumor effect of apatinib against melanoma and its potential mechanisms. Methods: We investigated the anti-tumor effects of apatinib alone or in combination with WZB117 on human melanoma cell lines (A375 and SK-MEL-28). The MTT assay determined cell viability and the half-maximal inhibitory concentration (IC50). Multiple drug effect/combination indexes (CI) analysis was conducted to assess interactions between apatinib and WZB117. Signal transducer and activator of transcription 3 (STAT3) pathway measured by western blotting and immunofluorescence staining. RNA expression analyses were performed using the reverse transcription-quantitative PCR method. Results: Apatinib and WZB117 showed dose and time-dependent growth inhibitory effects in both melanoma cells. The IC50 of apatinib at 48 h in A375 and SK-MEL-28 cells was 62.58 and 59.61 μM, respectively, while the IC50 of WZB117 was 116.85 and 113.91 μM, respectively. The CI values of the two drugs were 0.538 and 0.544, respectively, indicating a synergistic effect of apatinib combined with WZB117. We also found that glucose consumption and lactate production were suppressed by apatinib plus WZB117 in a dose-dependent manner, paralleled by reducing glycolytic enzyme pyruvate kinase M2 (PKM2). The potential mechanism of the combination was to suppress the phosphorylation of STAT3. Knockdown of STAT3 by siRNA inhibited the expression of PKM2, while the activation of STAT3 by IL-6 increased the expression of PKM2. The effects of IL-6 were attenuated by apatinib combined with WZB117 treatment. Conclusion: WZB117 enhanced the anti-tumor effect of apatinib against melanoma via modulating glycolysis by blocking the STAT3/PKM2 axis, which suggested the combination of apatinib with WZB117 could be a potential therapeutic candidate for melanoma.
LncRNA affects epigenetic reprogramming of porcine embryo development by regulating global epigenetic modification and the downstream gene SIN3A

The study of preimplantation development is of great significance to reproductive biology and regenerative medicine. With the development of high-throughput deep sequencing technology, it has been found that lncRNAs play a very important role in the regulation of embryonic development. In this study, key lncRNAs that regulate embryonic development were screened by analyzing the expression pattern of lncRNAs in porcine in vivo fertilization (IVV) embryos. By knocking down lncRNA expression in in vitro fertilization (IVF) embryos, we investigated its function and mechanism of regulating embryonic development. The results showed that the expression pattern of lncRNA was consistent with the time of gene activation. The lncRNAs were highly expressed in the 4-cell to blastocyst stage but barely expressed in the oocytes and 2-cell stage. So we speculated this part of lncRNAs may regulate gene expression. The lncRNA LOC102165808 (named lncT because the gene near this lncRNA is TFAP2C) was one of them. The knockdown (KD) of lncT inhibited embryonic development, resulting in decreased H3K4me3, H3K4me2, and H3K9me3, and increased DNA methylation. Meanwhile, RNAseq showed SIN3A was the top decreased gene in lncT-KD embryos. There was a severe blastocyst formation defect in SIN3A-KD embryos. Both lncT and SIN3A could affect NANOG and induce more cell apoptosis. In conclusion, the knockdown of lncT inhibits embryonic development by regulating H3K4me3, H3K4me2, DNA methylation, pluripotency gene, and apoptosis, and SIN3A is one of the downstream genes of lncT in regulating embryonic development.
Transcriptome and metabolome analyses reveal the responses of brown planthoppers to RH resistant rice cultivar

The brown planthopper (BPH) Nilaparvata lugens (Stål) (Hemiptera: Delphacidae) is one of the most destructive rice pests in Asia. The application of insect-resistant rice cultivars is currently one of the principal means of controlling BPH. Understanding the physiological response mechanisms of BPH feeding on insect-resistant rice is the key for maintaining rice yield. Here, we measured the ecological fitness and analyzed the whole-body transcriptome and metabolome of BPH reared on susceptible cultivar Taichung Native 1 (TN1) and resistant cultivar Rathu Heenati (RH). Our results showed that RH significantly decreased the survival rate, female adult weight, honeydew secretion, the number of eggs laid per female and fat content of BPH. We identified 333 upregulated and 486 downregulated genes in BPH feeding on RH. These genes were mainly involved in energy metabolism, amino acid metabolism, hormone synthesis and vitamin metabolism pathways. We also detected 145 differentially accumulated metabolites in BPH reared on RH plants compared to BPH reared on TN1 plants, including multiple carbohydrates, amino acids, lipids, and some nucleosides. Combined analyses of transcriptome and metabolome showed that five pathways, including starch, sucrose, and galactose metabolism, were altered. The network for these pathways was subsequently visualized. Our results provide insights into the mechanisms of metabolite accumulation in BPH feeding on the RH rice variety. The results could help us better understand how insect-resistant rice cultivars combat BPH infestation, which is important for the comprehensive management of BPH.
Carbon isotope and soluble metabolites reflect physiological status among contrasting faba bean genotypes in response to water deficit

Identification and validation of biomarkers and bioindicators to select genotypes with superior tolerance to water deficit (WD) under field conditions are paramount to plant breeding programs. However, the co-occurrence of different abiotic stresses such as WD, heat, and radiation makes it difficult to develop generalized protocols to monitor the physiological health of the plant system. The study assessed the most abundant carbohydrates and sugar alcohols in five faba bean (Vicia faba) genotypes under field conditions and the abundance of naturally occurring carbon isotopes in bulk leaf material to predict water use efficiency (WUE). Plant water status and biomass accumulation were also assessed. Among the accumulated sugars, inter-specific variation in glucose was most prevalent and was found at a higher concentration (8.52 mg g−1 leaf) in rainfed trial. myo-Inositol concentrations followed that of glucose accumulation in that the rainfed trial had higher amounts compared to the irrigated trial. WUE calculated from carbon isotope abundance was consistently offset with measured WUE from measurements of leaf gas exchange. All genotypes demonstrated significant relationships between predicted and measured WUE (p < 0.05) apart from control variety PBA Warda. Thus, bulk leaf-level carbon isotope abundance can be used to calculate WUE and used as an effective selection criterion for improving WUE in faba bean breeding programs under field conditions.
Clinical value of plasma and peripheral blood mononuclear cells Epstein–Barr Virus DNA dynamics on prognosis of allogeneic stem cell transplantation

The application of intracellular and extracellular Epstein–Barr virus (EBV) DNA in allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been poorly characterized. We conducted a combined prospective-retrospective study of 300 patients who underwent allo-HSCT between 2016 to 2019 in our center and monitored for EBV DNA within the first year after HSCT. Combining the optimal cut-off value of EBV DNA load (7.3×104 copies/106 cells) in peripheral blood mononuclear cells (PBMCs) and qualitative detection in plasma (400 copies/mL) allowed for the better differentiation of EBV-related posttransplant lymphoproliferative disorders (EBV-PTLD), with increased sensitivity (100%) and specificity (86%), and provided the effective risk stratification of EBV DNA level according to their impact on transplant outcomes. By multivariate analysis, patients with intermediate-level of EBV DNA load (low EBV DNA load in PBMCs or high load in PBMCs but negative in plasma) was associated with superior overall survival (HR 1.92, 95% CI 1.03-3.57, p=0.039) and lower transplant-related mortality (HR 3.35, 95% CI 1.31-8.58, p=0.012) compared to those with high-level (high load in PBMCs and positive in plasma). Notably, high EBV-level group had poor reconstitution of CD4+ and CD8+T cells, and both low and high EBV-level groups showed abnormally increase in IL-10 level within one year. Additionally, patients with peak EBV DNA load in PBMCs during 3-12 months had a higher incidence of chronic graft versus host disease (GVHD) than those within 3 months post transplantation (17.4% vs 13.7%, p=0.029). Collectively, EBV DNA in PBMCs can synergistically predict the risk of EBV-PTLD and GVHD. The intermediate-level of EBV DNA presented in plasma and PBMCs might contribute to a better reconstitution of T cells associated with favorable prognosis of allo-HSCT.
Retrospective analysis of clinical features and prognosis of nasopharyngeal carcinoma in children and adolescents

Objectives To investigate the clinical characteristics and prognosis of nasopharyngeal carcinoma (NPC) in children and adolescents in different age groups. Materials and methods The clinical data of 51 patients with NPC aged ≤ 18 years who were treated in Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2012 to May 2017 were retrospectively analyzed. The patients were divided into children group (≤12 years old) and adolescent group (12–18 years old) with 12 years old as the boundary. The clinical characteristics, diagnosis, treatment, and prognosis of the children and adolescent groups were compared. Results The symptoms of the first diagnosis in the children group were mainly nasal congestion (P = 0.043) and ear symptoms (P = 0.008). The diagnosis rate of nasopharyngeal biopsy in the children group was lower (P = 0.001), while the rate of diagnosis of cervical mass biopsy was significantly higher than that in the adolescent group (P = 0.009). The proportion of keratinizing squamous cell carcinoma of the children group was higher than that of the adolescent group (P = 0.006). There was no significant difference in TNM stage and risk stratification between the two groups, but the number of cases in the III-IVa children group who received induction chemotherapy + concurrent chemoradiotherapy was less than that in the adolescent group (P = 0.013). The proportion of radiotherapy in the upper and lower cervical lymph node drainage areas was lower than that in the adolescent group (P = 0.001). The percentage of recurrence and metastasis in the children group was higher than that in the adolescent group (P = 0.026). Conclusion The diagnosis in the children group depended on endoscopic biopsy and neck mass biopsy, and the proportion of keratinizing squamous cell carcinoma was higher. The number of cases of induction chemotherapy and concurrent chemoradiotherapy in the children group was less than that in the adolescent group, and the proportion of radiotherapy in the upper and lower cervical lymph node drainage areas was lower than that in the adolescent group. Clinically, it is necessary to improve the understanding of the clinical characteristics of children with NPC and take appropriate treatment strategies.