bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune-Protective Formulations and Process Strategies for Improved Survival and Function of Transplanted Islets
Authors: Shi Yannan , Zhao Ying-Zheng , Jiang Zhikai , Wang Zeqing , Wang Qian , Kou Longfa , Yao Qing
Published: July 2022

Type 1 diabetes (T1D) is an autoimmune disease caused by the immune system attacking and destroying insulin-producing β cells in the pancreas. Islet transplantation is becoming one of the most promising therapies for T1D patients. However, its clinical use is limited by substantial cell loss after islet infusion, closely related to immune reactions, including instant blood-mediated inflammatory responses, oxidative stress, and direct autoimmune attack. Especially the grafted islets are not only exposed to allogeneic immune rejection after transplantation but are also subjected to an autoimmune process that caused the original disease. Due to the development and convergence of expertise in biomaterials, nanotechnology, and immunology, protective strategies are being investigated to address this issue, including exploring novel immune protective agents, encapsulating islets with biomaterials, and searching for alternative implantation sites, or co-transplantation with functional cells. These methods have significantly increased the survival rate and function of the transplanted islets. However, most studies are still limited to animal experiments and need further studies. In this review, we introduced the immunological challenges for islet graft and summarized the recent developments in immune-protective strategies to improve the outcomes of islet transplantation.
SARS-Arena: Sequence and Structure-Guided Selection of Conserved Peptides from SARS-related Coronaviruses for Novel Vaccine Development
Authors: Rigo Mauricio Menegatti , Fasoulis Romanos , Conev Anja , Hall-Swan Sarah , Antunes Dinler Amaral , Kavraki Lydia E.
Published: July 2022

The pandemic caused by the SARS-CoV-2 virus, the agent responsible for the COVID-19 disease, has affected millions of people worldwide. There is constant search for new therapies to either prevent or mitigate the disease. Fortunately, we have observed the successful development of multiple vaccines. Most of them are focused on one viral envelope protein, the spike protein. However, such focused approaches may contribute for the rise of new variants, fueled by the constant selection pressure on envelope proteins, and the widespread dispersion of coronaviruses in nature. Therefore, it is important to examine other proteins, preferentially those that are less susceptible to selection pressure, such as the nucleocapsid (N) protein. Even though the N protein is less accessible to humoral response, peptides from its conserved regions can be presented by class I Human Leukocyte Antigen (HLA) molecules, eliciting an immune response mediated by T-cells. Given the increased number of protein sequences deposited in biological databases daily and the N protein conservation among viral strains, computational methods can be leveraged to discover potential new targets for SARS-CoV-2 and SARS-CoV-related viruses. Here we developed SARS-Arena, a user-friendly computational pipeline that can be used by practitioners of different levels of expertise for novel vaccine development. SARS-Arena combines sequence-based methods and structure-based analyses to (i) perform multiple sequence alignment (MSA) of SARS-CoV-related N protein sequences, (ii) recover candidate peptides of different lengths from conserved protein regions, and (iii) model the 3D structure of the conserved peptides in the context of different HLAs. We present two main Jupyter Notebook workflows that can help in the identification of new T-cell targets against SARS-CoV viruses. In fact, in a cross-reactive case study, our workflows identified a conserved N protein peptide (SPRWYFYYL) recognized by CD8+T-cells in the context of HLA-B7+. SARS-Arena is available athttps://github.com/KavrakiLab/SARS-Arena.
Curvularin Isolated From Phoma macrostoma Is an Antagonist of RhlR Quorum Sensing in Pseudomonas aeruginosa
Authors: Choi Ha-Young , Le Duc Dat , Kim Won-Gon
Published: July 2022

Quorum sensing (QS) is an attractive target for the treatment of multidrug-resistant Pseudomonas aeruginosa, against which new antibiotics are urgently needed. Because LasR is at the top of the QS hierarchy controlling Rhl and PQS systems, most QS inhibitors have been targeted to LasR. However, it has recently been reported that in clinical isolates of P. aeruginosa, LasR is frequently mutated and nonfunctional, and RhlR independently acts to produce virulent factors that maintain toxicity. Thus, for effective treatment of chronic cystic fibrosis infections, RhlR antagonists is needed to prevent the LasR-independent Rhl system, but RhlR antagonists have rarely been reported. In this study, we found that curvularin, an aromatic compound with a cyclized alkyl side chain isolated from Phoma macrostoma, at a low micromolar concentration of 1–30 μM potently and selectively inhibited pyocyanin and rhamnolipid production without affecting the cell viability of P. aeruginosa. Only high concentration (more over 100 μM) curvularin negligibly inhibited biofilm formation and elastase production, suggesting that curvularin at low concentrations selectively inhibits RhlR. The QS antagonism by curvularin was investigated in experiments using QS competition and signaling molecules assays with QS gene expression analysis, and the results showed that, indeed, at low concentrations, curvularin selectively antagonized RhlR; in contrast, it negligibly antagonized LasR only when applied at a high concentration. The exclusive RhlR antagonizing activity of curvularin at low concentrations was confirmed using QS mutants; specifically, curvularin at low concentrations inhibited pyocyanin and rhamnolipid production by selectively antagonizing N-butanoyl homoserine lactone (BHL)-activated RhlR. Moreover, by targeting RhlR, curvularin reduced the in vivo virulence of wild-type P. aeruginosa as well as lasR mutants in Caenorhabditis elegans. Overall, low-concentration curvularin is a pure RhlR antagonist in P. aeruginosa, and to the best of our knowledge, this is the first report describing an RhlR antagonist from natural resources. Hence, curvularin has great potential for the development of chronic P. aeruginosa infection therapeutics and for the study of RhlR function in the complex QS system.
Study Protocol for a Randomised Controlled Trial on Pulmonary Metastasectomy vs. Standard of Care in Colorectal Cancer Patients With ≥ 3 Lung Metastases (PUCC-Trial)
Authors: Schmid Severin , Becker Heiko , Fritsch Ralph , Bausch Johannes , Hunter Natalie , Jenkner Carolin , Hassan Mohamed , Passlick Bernward
Published: July 2022

This is a multicentre prospective randomised controlled trial for patients with 3 or more resectable pulmonary metastases from colorectal carcinoma. The study investigates the effects of pulmonary metastasectomy in addition to standard medical treatment in comparison to standard medical treatment plus possible local ablative measures such as SBRT. This trial is intended to demonstrate an overall survival difference in the group undergoing pulmonary metastasectomy. Further secondary and exploratory endpoints include quality of life (EORTC QLQ-C30, QLQ-CR29 and QLQ-LC29 questionnaires), progression-free survival and impact of mutational status. Due to the heterogeneity and complexity of the disease and treatment trajectories in metastasised colorectal cancer, well powered trials have been very challenging to design and execute. The goal of this study is to create a setting which allows treatment as close to the real life conditions as possible but under well standardised conditions. Based on previous trials, in which patient recruitment in the given setting hindered successful study completion, we decided to (1) restrict inclusion to patients with 3 or more metastases (since in case of lesser, surgery will probably be the preferred option) and (2) allow for real world standard of care (SOC) treatment options before and after randomisation including watchful waiting (as opposed to a predefined treatment protocol) and (3) possibility that patient can receive SOC externally (to reduce patient burden). Moreover, we chose to stipulate 12 weeks of systemic treatment prior to possible resection to further standardize treatment response and disease course over a certain period of time. Hence, included patients will be in the disease state of oligopersistence rather than primary oligometastatic. The trial was registered in the German Clinical Trials Register (DRKS-No.: DRKS00024727).
Adjuvant Chemoradiotherapy Versus Adjuvant Chemotherapy for Stage III Gastric or Gastroesophageal Junction Cancer After D2/R0 Resection
Authors: Shi Jinming , Kang Wenzhe , Tang Yuan , Li Ning , Jiang Liming , Yang Lin , Wang Shulian , Song Yongwen , Liu Yueping , Fang Hui , Lu Ningning , Qi Shunan , Chen Bo , Li Yexiong , Tian Yantao , Jin Jing
Published: July 2022

Purpose

To compare the survival benefit in the adjuvant chemoradiotherapy (CRT) group and chemotherapy (CT) group for stage III gastric or gastroesophageal junction (GEJ) cancer after D2/R0 resection.

Methods and Materials

From January 2011 to May 2018, 819 patients (CRT group: 215 patients, CT group: 604 patients) diagnosed as pathological stage III after D2/R0 resection were retrospectively collected and the survival and recurrence patterns were analyzed. The baseline characteristics were balanced based on propensity score matching (PSM). The survival benefit was compared between two groups using Kaplan–Meier analysis and Cox regression model.

Results

The 5-year overall survival (OS) rate in the CRT group was significantly higher than that in the CT group whether before or after the PSM. The multivariate Cox regression analysis identified the significant poor OS in patients with advanced TNM stage (P < 0.001) and patients who did not receive the adjuvant CRT (P = 0.008). For the recurrence patterns, 85 (39.5%) patients in the CRT group and 300 (49.7%) patients in the CT group were diagnosed as recurrence (P = 0.011). The regional recurrence in the CRT group was less than that in the CT group (20.5% vs. 35.1%, P = 0.028).

Conclusion

For patients diagnosed as stage III gastric cancer or gastroesophageal junction cancer, the addition of adjuvant chemoradiotherapy will significantly improve the overall survival and regional control.
Case Report: Lung Adenocarcinoma Initially Presenting With Cutaneous and Subcutaneous Metastases
Authors: Wang Jingjing , Wu Ruolin , Liu Fang , Yang Liu , Hu Fan , Wu Zhijian , Gao Zairong , Xia Xiaotian
Published: July 2022

Cutaneous and subcutaneous soft tissue metastases are rare in lung adenocarcinoma and suggest poor prognosis. We report a patient with lung adenocarcinoma who initially presented with cutaneous and subcutaneous metastases to the abdomen that were initially presumed to be herpes zoster and an occult subcutaneous soft tissue mass. Because the lesions progressed over 3 weeks despite routine herpes zoster treatment, magnetic resonance imaging was performed and showed a presumed sarcoma; however, 18F-fluourodeoxyglucose positron emission tomography/computed tomography demonstrated pulmonary lesions. Biopsy of the abdominal lesion confirmed poorly differentiated lung adenocarcinoma. Early diagnosis of soft tissue metastasis can be difficult. Clinicians should suspect internal organ malignancy when a progressive cutaneous or subcutaneous soft tissue lesion is encountered.
The Influence of 0.5% Tropicamide on Anterior Segment Parameters With CASIA2 in Emmetropic, Myopic, and Hyperopic Eyes
Authors: Lin Feng , Wang Yuliang , Liu Yujia , Qu Xiaomei , Zhou Xingtao
Published: July 2022

Aim: To evaluate the effects of 0.5% tropicamide on anterior segment parameters with the CASIA2 imaging device in emmetropic, myopic, and hyperopic eyes.

Methods: In this prospective study, a total of 125 subjects (34 emmetropic subjects, 57 myopic subjects, and 34 hyperopic subjects) at the Shanghai Eye and ENT Hospital of Fudan University were recruited from June 2021 to September 2021. The 0.5% tropicamide solution was used once every 5 min a total of 5 times for cycloplegia. The anterior segment parameters were recorded by CASIA2 before and after cycloplegia. Changes in anterior segment parameters were compared among the three refractive groups.

Results: Crystalline lens rise (CLR) and crystalline lens thickness (CLT) significantly decreased in all three refractive groups after cycloplegia (all p < 0.01). The anterior radius of lens (ARL) and anterior chamber depth (ACD) significantly increased in all three refractive groups after cycloplegia (all p < 0.01). Posterior radius of lens (PRL) significantly increased in hyperopic eyes after cycloplegia (p < 0.01) while it remained unchanged in emmetropic eyes and myopic eyes. Central corneal thickness (CCT), anterior chamber width (ACW), lens decentration (LD), and lens tilt (LT) remained unchanged after cycloplegia in all three refractive groups (all p > 0.05). Changes in CLR, CLT, ARL, PRL, and ACD in hyperopic eyes were greater than those in emmetropic eyes and myopic eyes (all p < 0.05).

Conclusion: Apart from various changes in anterior segment parameters after application by 0.5% tropicamide in all three refractive groups, significant changes in CLR, CLT, ARL, PRL, and ACD in hyperopic eyes should be noted for proper clinical interpretation.
Genome-Wide Identification, Characterization, and Expression Profile Analysis of CONSTANS-like Genes in Woodland Strawberry (Fragaria vesca)
Authors: Zhao Xinyong , Yu Fuhai , Guo Qing , Wang Yu , Zhang Zhihong , Liu Yuexue
Published: July 2022

CONSTANS-like (CO-like) gene is one of the most important regulators in the flowering process of the plant, playing a core role in the photoperiodic flowering induction pathway. In this study, we identified 10 distinct CO-like genes (FveCOs) in woodland strawberry (Fragaria vesca). They were classified into three groups with specific gene structure characteristics or protein domains in each group. The effect of selection pressure on the FveCOs in the woodland strawberry was tested by Ka/Ks, and it was shown that the evolution rate of FveCOs was controlled by purification selection factors. Intraspecific synteny analysis of woodland strawberry FveCOs showed that at least one duplication event existed in the gene family members. Collinearity analysis of woodland strawberry genome with genomes of Arabidopsis, rice (Oryza sativa), and apple (Malus × domestica) showed that CO-like genes of F. vesca and Malus × domestica owned higher similarity for their similar genomes compared with those of other two species. The FveCOs showed different tissue-specific expression patterns. Moreover, real-time quantitative PCR results revealed that the expressions of the most FveCOs followed a 24-h rhythm oscillation under both long-day (LD) and short-day (SD) conditions. Further expression analysis showed that the individual expression changing profile of FveCO3 and FveCO5 was opposite to each other under both LD and SD conditions. Moreover, the expression of FveCO3 and FveCO5 was both negatively correlated with the flowering time variation of the woodland strawberry grown under LD and SD conditions, indicating their potential vital roles in the photoperiodic flowering regulation. Further protein interaction network analysis also showed that most of the candidate interaction proteins of FveCO3 and FveCO5 were predicted to be the flowering regulators. Finally, LUC assay indicated that both FveCO3 and FveCO5 could bind to the promoter of FveFT1, the key regulator of flowering regulation in the woodland strawberry, and thus activate its expression. Taken together, this study laid a foundation for understanding the exact roles of FveCOs in the reproductive development regulation of the woodland strawberry, especially in the photoperiodic flowering process.
Unraveling the Mechanism of Purple Leaf Formation in Brassica napus by Integrated Metabolome and Transcriptome Analyses
Authors: Li Haibo , Du Yi , Zhang Jinkun , Feng Huimin , Liu Jianguo , Yang Guiling , Zhu Yunna
Published: July 2022

Brassica napus as both oilseed and vegetable, is widely cultivated in China. The purple leaf of B. napus is rich in anthocyanins and can provide valuable nutrients. Although several high-anthocyanin cultivars have been reported, the molecular mechanism underlying anthocyanin biosynthesis in B. napus remains lesser-known. Therefore, in this study, we conducted integrative metabolome and transcriptome analyses in three B. napus cultivars with different leaf colors. Overall, 39 flavonoids were identified (including 35 anthocyanins), and 22 anthocyanins were differentially accumulated in the leaves, contributing to the different leaf colors. Cyanidin-3,5,3’-O-triglucoside was confirmed as the main contributor of the purple leaf phenotype. Meanwhile, other anthocyanins may play important roles in deepening the color of B. napus leaves. A total of 5,069 differentially expressed genes (DEGs) and 32 overlapping DEGs were identified by RNA-sequencing; hence, the correlation between anthocyanin content and DEG expression levels was explored. Two structural genes (DFR and ANS), three GSTs (homologous to TT19), and 68 differentially expressed transcription factors (TFs), especially MYB-related TFs and WRKY44, were identified in three B. napus varieties characterized by different leaf color, thereby indicating that these genes may contribute to anthocyanin biosynthesis, transport, or accumulation in B. napus leaves. The findings of study provide important insights that may contribute to gaining a better understanding of the transcriptional regulation of anthocyanin metabolism in B. napus.
Nitrogen-Induced Changes in Soil Environmental Factors Are More Important Than Nitrification and Denitrification Gene Abundance in Regulating N2O Emissions in Subtropical Forest Soils
Authors: Qiu Qingyan , Mgelwa Abubakari Said , Jin Shaofei , Hu Yalin
Published: July 2022

Subtropical regions are currently experiencing a dramatic increase in nitrogen (N) deposition; however, the contributions of nitrification and denitrification processes to soil N2O emissions and the underlying mechanisms under increasing N deposition remain unclear. Therefore, a 15N-tracing laboratory experiment with four N application rates (0, 12.5, 25, and 50 μg 15N g–1 soil) was conducted to investigate the response of nitrification- and denitrification-derived N2O to N additions in an evergreen broad-leaved forest (BF) and a Pinus forest (PF) in the Wuyi Mountains in southeastern China. Moreover, the abundance of functional genes related to nitrification (amoA), denitrification (nirK, nirS, and nosZ), and soil properties were measured to clarify the underlying mechanisms. Results showed that nitrification-derived N2O emissions were generally decreased with increasing N input. However, denitrification-derived N2O emissions were a non-linear response to N additions, with maximum N2O emissions at the middle N application rate. Denitrification-derived N2O was the dominant pathway of N2O production, accounting for 64 to 100% of the total N2O fluxes. Soil NH4+-N content and pH were the predominant factors in regulating nitrification-derived N2O emissions in BF and PF, respectively. Soil pH and the nirS abundance contributed the most to the variations of denitrification-derived N2O emissions in BF and PF, respectively. Our results suggest that N application has the potential to increase the contribution of denitrification to N2O production in subtropical forest soils. Changes in soil chemical properties induced by N addition are more important than the abundance of nitrification and denitrification functional genes in regulating soil nitrification- and denitrification-derived N2O emissions.
Harnessing the Known and Unknown Impact of Nanotechnology on Enhancing Food Security and Reducing Postharvest Losses: Constraints and Future Prospects
Authors: Fadiji Ayomide Emmanuel , Mthiyane Doctor Mziwenkosi Nhlanhla , Onwudiwe Damian C. , Babalola Olubukola Oluranti
Published: July 2022

Due to the deterioration of natural resources, low agricultural production, significant postharvest losses, no value addition, and a rapid increase in population, the enhancement of food security and safety in underdeveloped countries is becoming extremely tough. Efforts to incorporate the latest technology are now emanating from scientists globally in order to boost supply and subsequently reduce differences between the demand and the supply chain for food production. Nanotechnology is a unique technology that might increase agricultural output by developing nanofertilizers, employing active pesticides and herbicides, regulating soil features, managing wastewater and detecting pathogens. It is also suitable for processing food, as it boosts food production with high market value, improves its nutrient content and sensory properties, increases its safety, and improves its protection from pathogens. Nanotechnology can also be beneficial to farmers by assisting them in decreasing postharvest losses through the extension of the shelf life of food crops using nanoparticles. This review presents current data on the impact of nanotechnology in enhancing food security and reducing postharvest losses alongside the constraints confronting its application. More research is needed to resolve this technology’s health and safety issues.
An AuNPs-Based Fluorescent Sensor with Truncated Aptamer for Detection of Sulfaquinoxaline in Water
Authors: Chen Xingyue , Yang Lulan , Tang Jiaming , Wen Xu , Zheng Xiaoling , Chen Lingling , Li Jiaqi , Xie Yong , Le Tao
Published: July 2022

Herein, we developed a novel truncation technique for aptamer sequences to fabricate highly sensitive aptasensors based on molecular docking and molecular dynamics simulations. The binding mechanism and energy composition of the aptamer/sulfaquinoxaline (SQX) complexes were investigated. We successfully obtained a new SQX-specific aptamer (SBA28-1: CCCTAGGGG) with high affinity (Kd = 27.36 nM) and high specificity determined using graphene oxide. This aptamer has a unique stem-loop structure that can bind to SQX. Then, we fabricated a fluorescence aptasensor based on SBA28-1, gold nanoparticles (AuNPs), and rhodamine B (RhoB) that presented a good linear range of 1.25–160 ng/mL and a limit of detection of 1.04 ng/mL. When used to analyze water samples, the aptasensor presented acceptable recovery rates of 93.1–100.1% and coefficients of variation (CVs) of 2.2–10.2%. In conclusion, the fluorescence aptasensor can accurately and sensitively detect SQX in water samples and has good application prospects.
Human Enzyme PADI4 Binds to the Nuclear Carrier Importin α3
Authors: Neira José L. , Rizzuti Bruno , Abián Olga , Araujo-Abad Salomé , Velázquez-Campoy Adrián , de Juan Romero Camino
Published: July 2022

PADI4 is a peptidyl-arginine deiminase (PADI) involved in the conversion of arginine to citrulline. PADI4 is present in macrophages, monocytes, granulocytes, and several cancer cells. It is the only PADI family member observed within both the nucleus and the cytoplasm. PADI4 has a predicted nuclear localization sequence (NLS) comprising residues Pro56 to Ser83, to allow for nuclear translocation. Recent predictors also suggest that the region Arg495 to Ile526 is a possible NLS. To understand how PADI4 is involved in cancer, we studied the ability of intact PADI4 to bind importin α3 (Impα3), a nuclear transport factor that plays tumor-promoting roles in several cancers, and its truncated species (ΔImpα3) without the importin-binding domain (IBB), by using fluorescence, circular dichroism (CD), and isothermal titration calorimetry (ITC). Furthermore, the binding of two peptides, encompassing the first and the second NLS regions, was also studied using the same methods and molecular docking simulations. PADI4 interacted with both importin species, with affinity constants of ~1–5 µM. The isolated peptides also interacted with both importins. The molecular simulations predict that the anchoring of both peptides takes place in the major binding site of Impα3 for the NLS of cargo proteins. These findings suggest that both NLS regions were essentially responsible for the binding of PADI4 to the two importin species. Our data are discussed within the framework of a cell mechanism of nuclear transport that is crucial in cancer.
Progress of Imaging in Diabetic Retinopathy—From the Past to the Present
Authors: Horie Shintaro , Ohno-Matsui Kyoko
Published: July 2022

Advancement of imaging technology in retinal diseases provides us more precise understanding and new insights into the diseases’ pathologies. Diabetic retinopathy (DR) is one of the leading causes of sight-threatening retinal diseases worldwide. Colour fundus photography and fluorescein angiography have long been golden standard methods in detecting retinal vascular pathology in this disease. One of the major advancements is macular observation given by optical coherence tomography (OCT). OCT dramatically improves the diagnostic quality in macular edema in DR. The technology of OCT is also applied to angiography (OCT angiograph: OCTA), which enables retinal vascular imaging without venous dye injection. Similar to OCTA, in terms of their low invasiveness, single blue color SLO image could be an alternative method in detecting non-perfused areas. Conventional optical photography has been gradually replaced to scanning laser ophthalmoscopy (SLO), which also make it possible to produce spectacular ultra-widefield (UWF) images. Since retinal vascular changes of DR are found in the whole retina up to periphery, it would be one of the best targets in UWF imaging. Additionally, evolvement of artificial intelligence (AI) has been applied to automated diagnosis of DR, and AI-based DR management is one of the major topics in this field. This review is trying to look back on the progress of imaging of DR comprehensively from the past to the present.
Clinical Application of Diffusion Tensor Imaging for a Brachial Plexus Injury
Authors: Vara Giulio , Tuzzato Gianmarco , Bianchi Giuseppe , Miceli Marco , Spinardi Luca , Golfieri Rita , Rinaldi Raffaella , Facchini Giancarlo
Published: July 2022

Brachial plexus injuries are commonly diagnosed clinically, as conventional imaging has a low sensitivity. In recent years, diffusion tensor imaging has established a clinical role in the study of the central nervous system and, while still presenting some limitations due to the technical complexity of the acquisition method, is showing promising results when applied to peripheral nerves. Moreover, deterministic fiber tracking with the Euler’s method and multishell acquisition are two novel advances in the field which contribute to enhancing the reliability of the technique reducing the respiratory and inhomogeneity artifacts in this “magnetically complex” region, and better isolating the fibers in a heterogeneous territory. Here, we report a case of brachial plexus traumatic injury, a healthy reference subject, and details on the acquisition protocol of the reconstruction algorithm.
Radiomics Diagnostic Tool Based on Deep Learning for Colposcopy Image Classification
Authors: Jiménez Gaona Yuliana , Castillo Malla Darwin , Vega Crespo Bernardo , Vicuña María José , Neira Vivian Alejandra , Dávila Santiago , Verhoeven Veronique
Published: July 2022

Background: Colposcopy imaging is widely used to diagnose, treat and follow-up on premalignant and malignant lesions in the vulva, vagina, and cervix. Thus, deep learning algorithms are being used widely in cervical cancer diagnosis tools. In this study, we developed and preliminarily validated a model based on the Unet network plus SVM to classify cervical lesions on colposcopy images. Methodology: Two sets of images were used: the Intel & Mobile ODT Cervical Cancer Screening public dataset, and a private dataset from a public hospital in Ecuador during a routine colposcopy, after the application of acetic acid and lugol. For the latter, the corresponding clinical information was collected, specifically cytology on the PAP smear and the screening of human papillomavirus testing, prior to colposcopy. The lesions of the cervix or regions of interest were segmented and classified by the Unet and the SVM model, respectively. Results: The CAD system was evaluated for the ability to predict the risk of cervical cancer. The lesion segmentation metric results indicate a DICE of 50%, a precision of 65%, and an accuracy of 80%. The classification results’ sensitivity, specificity, and accuracy were 70%, 48.8%, and 58%, respectively. Randomly, 20 images were selected and sent to 13 expert colposcopists for a statistical comparison between visual evaluation experts and the CAD tool (p-value of 0.597). Conclusion: The CAD system needs to improve but could be acceptable in an environment where women have limited access to clinicians for the diagnosis, follow-up, and treatment of cervical cancer; better performance is possible through the exploration of other deep learning methods with larger datasets.
Underlying Mechanisms of Reductive Amination on Pd-Catalysts: The Unique Role of Hydroxyl Group in Generating Sterically Hindered Amine
Authors: Hong Zeng , Ge Xin , Zhou Shaodong
Published: July 2022

Pd nanospecies supported on porous g-C3N4 nanosheets were prepared for efficient reductive amination reactions. The structures of the catalysts were characterized via FTIR, XRD, XPS, SEM, TEM, and TG analysis, and the mechanisms were investigated using in situ ATR–FTIR spectroscopic analysis complemented by theoretical calculation. It transpired that the valence state of the Pd is not the dominating factor; rather, the hydroxyl group of the Pd(OH)2 cluster is crucial. Thus, by passing protons between different molecules, the hydroxyl group facilitates both the generation of the imine intermediate and the reduction of the C=N unit. As a result, the sterically hindered amines can be obtained at high selectivity (>90%) at room temperature.
Genome-Wide Analysis of the HDAC Gene Family and Its Functional Characterization at Low Temperatures in Tartary Buckwheat (Fagopyrum tataricum)
Authors: Hou Yukang , Lu Qi , Su Jianxun , Jin Xing , Jia Changfu , An Lizhe , Tian Yongke , Song Yuan
Published: July 2022

Histone deacetylases (HDACs), widely found in various types of eukaryotic cells, play crucial roles in biological process, including the biotic and abiotic stress responses in plants. However, no research on the HDACs of Fagopyrum tataricum has been reported. Here, 14 putative FtHDAC genes were identified and annotated in Fagopyrum tataricum. Their gene structure, motif composition, cis-acting elements, phylogenetic relationships, protein structure, alternative splicing events, subcellular localization and gene expression pattern were investigated. The gene structure showed FtHDACs were classified into three subfamilies. The promoter analysis revealed the presence of various cis-acting elements responsible for hormone, abiotic stress and developmental regulation for the specific induction of FtHDACs. Two duplication events were identified in FtHDA6-1, FtHDA6-2, and FtHDA19. The expression patterns of FtHDACs showed their correlation with the flavonoid synthesis pathway genes. In addition, alternative splicing, mRNA enrichment profiles and transgenic analysis showed the potential role of FtHDACs in cold responses. Our study characterized FtHDACs, providing a candidate gene family for agricultural breeding and crop improvement.
Measuring Molecular Diffusion in Dynamic Subcellular Nanostructures by Fast Raster Image Correlation Spectroscopy and 3D Orbital Tracking
Authors: Begarani Filippo , D’Autilia Francesca , Ferri Gianmarco , Pesce Luca , Azzarello Fabio , De Lorenzi Valentina , Durso William , Del Grosso Ambra , Cecchini Marco , Cardarelli Francesco
Published: July 2022

Here we provide demonstration that fast fluorescence fluctuation spectroscopy is a fast and robust approach to extract information on the dynamics of molecules enclosed within subcellular nanostructures (e.g., organelles or vesicles) which are also moving in the complex cellular environment. In more detail, Raster Image Correlation Spectroscopy (RICS) performed at fast timescales (i.e., microseconds) reveals the fast motion of fluorescently labeled molecules within two exemplary dynamic subcellular nanostructures of biomedical interest, the lysosome and the insulin secretory granule (ISG). The measurement of molecular diffusion is then used to extract information on the average properties of subcellular nanostructures, such as macromolecular crowding or molecular aggregation. Concerning the lysosome, fast RICS on a fluorescent tracer allowed us to quantitatively assess the increase in organelle viscosity in the pathological condition of Krabbe disease. In the case of ISGs, fast RICS on two ISG-specific secreting peptides unveiled their differential aggregation propensity depending on intragranular concentration. Finally, a combination of fast RICS and feedback-based 3D orbital tracking was used to subtract the slow movement of subcellular nanostructures from the fast diffusion of molecules contained within them and independently validate the results. Results presented here not only demonstrate the acquired ability to address the dynamic behavior of molecules in moving, nanoscopic reference systems, but prove the relevance of this approach to advance our knowledge on cell function at the subcellular scale.
Light Triggers the Antiproliferative Activity of Naphthalimide-Conjugated (η6-arene)ruthenium(II) Complexes
Authors: Bisceglie Franco , Pelosi Giorgio , Orsoni Nicolò , Pioli Marianna , Carcelli Mauro , Pelagatti Paolo , Pinelli Silvana , Sadler Peter J.
Published: July 2022

We report the synthesis and characterization of three half-sandwich Ru(II) arene complexes [(η6-arene)Ru(N,N′)L][PF6]2 containing arene = p-cymene, N,N′ = bipyridine, and L = pyridine meta- with methylenenaphthalimide (C1), methylene(nitro)naphthalimide (C2), or methylene(piperidinyl)naphthalimide (C3). The naphthalimide acts as an antenna for photoactivation. After 3 h of irradiation with blue light, the monodentate pyridyl ligand had almost completely dissociated from complex C3, which contains an electron donor on the naphthalimide ring, whereas only 50% dissociation was observed for C1 and C2. This correlates with the lower wavelength and strong absorption of C3 in this region of the spectrum (λmax = 418 nm) compared with C1 and C2 (λmax = 324 and 323 nm, respectively). All the complexes were relatively non-toxic towards A549 human lung cancer cells in the dark, but only complex C3 exhibited good photocytoxicity towards these cancer cells upon irradiation with blue light (IC50 = 10.55 ± 0.30 μM). Complex C3 has the potential for use in photoactivated chemotherapy (PACT).
Differential Cellular Balance of Olfactory and Vomeronasal Epithelia in a Transgenic BACHD Rat Model of Huntington’s Disease
Authors: Krysewski Lina-Marielle , Power Guerra Nicole , Glatzel Annika , Holzmann Carsten , Antipova Veronica , Schmitt Oliver , Yu-Taeger Libo , Nguyen Huu Phuc , Wree Andreas , Witt Martin
Published: July 2022

Background. For neurodegenerative diseases such as Huntington’s disease (HD), early diagnosis is essential to treat patients and delay symptoms. Impaired olfaction, as observed as an early symptom in Parkinson´s disease, may also constitute a key symptom in HD. However, there are few reports on olfactory deficits in HD. Therefore, we aimed to investigate, in a transgenic rat model of HD: (1) whether general olfactory impairment exists and (2) whether there are disease-specific dynamics of olfactory dysfunction when the vomeronasal (VNE) and main olfactory epithelium (MOE) are compared. Methods. We used male rats of transgenic line 22 (TG22) of the bacterial artificial chromosome Huntington disease model (BACHD), aged 3 days or 6 months. Cell proliferation, apoptosis and macrophage activity were examined with immunohistochemistry in the VNE and MOE. Results. No differences were observed in cellular parameters in the VNE between the groups. However, the MOE of the 6-month-old HD animals showed a significantly increased number of mature olfactory receptor neurons. Other cellular parameters were not affected. Conclusions. The results obtained in the TG22 line suggest a relative stability in the VNE, whereas the MOE seems at least temporarily affected.
Molecular Modelling of NONO and SFPQ Dimerization Process and RNA Recognition Mechanism
Authors: Laurenzi Tommaso , Palazzolo Luca , Taiana Elisa , Saporiti Simona , Ben Mariem Omar , Guerrini Uliano , Neri Antonino , Eberini Ivano
Published: July 2022

NONO and SFPQ are involved in multiple nuclear processes (e.g., pre-mRNA splicing, DNA repair, and transcriptional regulation). These proteins, along with NEAT1, enable paraspeckle formation, thus promoting multiple myeloma cell survival. In this paper, we investigate NONO and SFPQ dimer stability, highlighting the hetero- and homodimer structural differences, and model their interactions with RNA, simulating their binding to a polyG probe mimicking NEAT1guanine-rich regions. We demonstrated in silico that NONO::SFPQ heterodimerization is a more favorable process than homodimer formation. We also show that NONO and SFPQ RRM2 subunits are primarily required for protein–protein interactions with the other DBHS protomer. Simulation of RNA binding to NONO and SFPQ, beside validating RRM1 RNP signature importance, highlighted the role of β2 and β4 strand residues for RNA specific recognition. Moreover, we demonstrated the role of the NOPS region and other protomer’s RRM2 β2/β3 loop in strengthening the interaction with RNA. Our results, having deepened RNA and DBHS dimer interactions, could contribute to the design of small molecules to modulate the activity of these proteins. RNA-mimetics, able to selectively bind to NONO and/or SFPQ RNA-recognition site, could impair paraspeckle formation, thus representing a first step towards the discovery of drugs for multiple myeloma treatment.
Targeting the Microenvironment for Treating Multiple Myeloma
Authors: Neumeister Peter , Schulz Eduard , Pansy Katrin , Szmyra Marta , Deutsch Alexander JA
Published: July 2022

Multiple myeloma (MM) is a malignant, incurable disease characterized by the expansion of monoclonal terminally differentiated plasma cells in the bone marrow. MM is consistently preceded by an asymptomatic monoclonal gammopathy of undetermined significance, and in the absence of myeloma defining events followed by a stage termed smoldering multiple myeloma (SMM), which finally progresses to active myeloma if signs of organ damage are present. The reciprocal interaction between tumor cells and the tumor microenvironment plays a crucial role in the development of MM and the establishment of a tumor-promoting stroma facilitates tumor growth and myeloma progression. Since myeloma cells depend on signals from the bone marrow microenvironment (BMME) for their survival, therapeutic interventions targeting the BMME are a novel and successful strategy for myeloma care. Here, we describe the complex interplay between myeloma cells and the cellular components of the BMME that is essential for MM development and progression. Finally, we present BMME modifying treatment options such as anti-CD38 based therapies, immunomodulatory drugs (IMiDs), CAR T-cell therapies, bispecific antibodies, and antibody-drug conjugates which have significantly improved the long-term outcome of myeloma patients, and thus represent novel therapeutic standards.
Analysis of Variability of Functionals of Recombinant Protein Production Trajectories Based on Limited Data
Authors: Liao Shuting , Macharoen Kantharakorn , McDonald Karen A. , Nandi Somen , Paul Debashis
Published: July 2022

Making statistical inference on quantities defining various characteristics of a temporally measured biochemical process and analyzing its variability across different experimental conditions is a core challenge in various branches of science. This problem is particularly difficult when the amount of data that can be collected is limited in terms of both the number of replicates and the number of time points per process trajectory. We propose a method for analyzing the variability of smooth functionals of the growth or production trajectories associated with such processes across different experimental conditions. Our modeling approach is based on a spline representation of the mean trajectories. We also develop a bootstrap-based inference procedure for the parameters while accounting for possible multiple comparisons. This methodology is applied to study two types of quantities—the “time to harvest” and “maximal productivity”—in the context of an experiment on the production of recombinant proteins. We complement the findings with extensive numerical experiments comparing the effectiveness of different types of bootstrap procedures for various tests of hypotheses. These numerical experiments convincingly demonstrate that the proposed method yields reliable inference on complex characteristics of the processes even in a data-limited environment where more traditional methods for statistical inference are typically not reliable.
Rashba Splitting and Electronic Valley Characteristics of Janus Sb and Bi Topological Monolayers
Authors: Gong Qi , Zhang Guiling
Published: July 2022

Janus Sb and Bi monolayers as a new class of 2D topological insulator materials, which could be fulfilled by asymmetrical functionalizations with methyl or hydroxyl, are demonstrated by first-principles spin–orbit coupling (SOC) electronic structure calculations to conflate nontrivial topology, Rashba splitting and valley-contrast circular dichroism. Cohesive energies and phonon frequency dispersion spectra indicate that all Janus Sb and Bi monolayers possess a structural stability in energetic statics but represent virtual acoustic phonon vibrations of the hydrogen atoms passivating on monolayer surfaces. Band structures of Janus Sb and Bi monolayers and their nanoribbons demonstrate they are nontrivial topological insulators. Rashba spin splitting at G point in Brillouin zone of Janus Bi monolayers arises from the strong SOC px and py orbitals of Bi bonding atoms together with the internal out-of-plane electric field caused by asymmetrical functionalization. Janus Sb and Bi monolayers render direct and indirect giant bandgaps, respectively, which are derived from the strong SOC px and py orbitals at band-valley Brillouin points K and K′ where valley-selective circular dichroism of spin valley Hall insulators is also exhibited.
Evaluation of the Impact of Pregnancy-Associated Factors on the Quality of Wharton’s Jelly-Derived Stem Cells Using SOX2 Gene Expression as a Marker
Authors: Gil-Kulik Paulina , Świstowska Małgorzata , Krzyżanowski Arkadiusz , Petniak Alicja , Kwaśniewska Anna , Płachno Bartosz J. , Galkowski Dariusz , Bogucka-Kocka Anna , Kocki Janusz
Published: July 2022

SOX2 is a recognized pluripotent transcription factor involved in stem cell homeostasis, self-renewal and reprogramming. It belongs to, one of the SRY-related HMG-box (SOX) family of transcription factors, taking part in the regulation of embryonic development and determination of cell fate. Among other functions, SOX2 promotes proliferation, survival, invasion, metastasis, cancer stemness, and drug resistance. SOX2 interacts with other transcription factors in multiple signaling pathways to control growth and survival. The aim of the study was to determine the effect of a parturient’s age, umbilical cord blood pH and length of pregnancy on the quality of stem cells derived from Wharton’s jelly (WJSC) by looking at birth weight and using SOX2 gene expression as a marker. Using qPCR the authors, evaluated the expression of SOX2 in WJSC acquired from the umbilical cords of 30 women right after the delivery. The results showed a significant correlation between the birth weight and the expression of SOX2 in WJSC in relation to maternal age, umbilical cord blood pH, and the length of pregnancy. The authors observed that the younger the woman and the lower the umbilical cord blood pH, the earlier the delivery occurs, the lower the birth weight and the higher SOX2 gene expression in WJSC. In research studies and clinical applications of regenerative medicine utilizing mesenchymal stem cells derived from Wharton’s Jelly of the umbilical cord, assessment of maternal and embryonic factors influencing the quality of cells is critical.
The Oldest Representatives of Tree Crickets (Orthoptera: Gryllidae; Oecanthinae) from Northern Myanmar
Authors: Yuan Wei , Zheng Cheng-Jie , Zheng Yan-Na , Ma Li-Bin , Gu Jun-Jie
Published: July 2022

The abundance of insects in Burmese amber illustrates a highly diverse insect community of the mid-Cretaceous, but the records of crickets are relatively rare. Here, we erect two new genera with two new species, Birmanioecanthus haplostichus gen. et sp. nov. and Apiculatus cretaceus gen. et sp. nov., based on two new specimens from northern Myanmar amber. These new species can be assigned to the subfamily Oecanthinae (Orthoptera: Gryllidae) by their prognathous head, slender body and metatibiae, and protibiae with large tympana. These new findings are the first and earliest fossil record of tree crickets and shed light on the evolution of Oecanithinae.
The Genetic Diversity in Thereuonema tuberculata (Wood, 1862) (Scutigeromorpha: Scutigeridae) and the Phylogenetic Relationship of Scutigeromorpha Using the Mitochondrial Genome
Authors: Yang Yong-Mei , Zhang Li-Hua , Lin Yi-Jie , Zheng Yi-Meng , Jin Wan-Ting , Storey Kenneth B. , Yu Dan-Na , Zhang Jia-Yong
Published: July 2022

Based on morphological characteristics to make species identification, the cryptic species of the Scutigeromorpha can be greatly underestimated. The mitochondrial genome provides a desirable tool for the biological identifications and the discovery of the cryptic species. The capacity to acquire mitochondrial genome sequences has substantially improved in recent years using next-generation sequencing (NGS) technology. On the basis of the next-generation sequencing, we obtained four complete mitochondrial genomes of Thereuonema tuberculata (Wood, 1862) from Nanyang, Henan Province (NY), Nanchang, Jiangxi Province (NC), Jinan, Shandong Province (JN), and Dali, Yunnan Province (DL) in China with GenBank numbers OK513221, OL449685, ON058988 and ON058989, respectively. The lengths of the four mitochondrial genomes ranged from 14,903 to 14,909 bp. The composition and order of genes of the four mitochondrial genomes were identical to the published mitochondrial genome of Scutigera coleoptrata (Linnaeus, 1758) (Scutigeromorpha: Scutigerdae). It was the first time that the tandem repeats in the control region were detected in Scutigeromorpha. We also calculated the corrected pairwise genetic distance of four complete mitochondrial genomes of T. tuberculata, ranging from 7.7 to 15.2%. The results showed that the T.tuberculata NC belonged to the typical sample of T. tuberculata, and T. tuberculata DL was hypothesized as a cryptic species of T. tuberculata. Meanwhile, T. tuberculata NY and T. tuberculata JN were hypothesized as potential cryptic species of T. tuberculata in this study. In both BI and ML trees, the monophyly of Scutigeromorpha, Scolopendromorpha, Geophilomorpha, and Lithobiomorpha was forcefully advocated. Moreover, Scutigeromorpha was recovered as the sister clade of (Scolopendromorpha + (Lithobiomorpha + Geophilomorpha)). Four specimens of T. tuberculata were clustered into one clade, which was the sister to the clade of S. coleoptrata.