bluuebunny/crossref_metadata_2025 huggingface dataset:
Histology Classification Highlights Differences in Efficacy of S-1 versus Capecitabine, in Combination with Cisplatin, for HER2-Negative Unresectable Advanced or Recurrent Gastric Cancer with Measurable Disease
Authors: Kawakami Hisato , Nishikawa Kazuhiro , Shimokawa Toshio , Fujitani Kazumasa , Tamura Shigeyuki , Endo Shunji , Kobayashi Michiya , Kawada Junji , Kurokawa Yukinori , Tsuburaya Akira , Yoshikawa Takaki , Sakamoto Junichi , Satoh Taroh ,   on behalf of the HERBIS-2, HERBIS-4A and XParTS II Study Investigators
Published: November 2022

It has been suggested that the therapeutic efficacy of S-1 + cisplatin (SP) and capecitabine + cisplatin (XP) may differ depending on the histology of the tumor, but no clear evidence exists. Individual participant data were obtained from three randomized phase II trials in which such patients received either SP (S-1 [40–60 mg twice daily for 21 days] plus cisplatin [60 mg/m2 on day 8], every 5 weeks) or XP (capecitabine [1000 mg/m2 twice daily for 14 days] plus cisplatin [80 mg/m2 on day 1], every 3 weeks). A total of 162 patients were included, with 79 patients in the SP arm and 83 patients in the XP arm. Although there was also no difference between arms in ORR according to histological classification, differentiated tumors showed a significantly better OS (but not PFS) for SP versus XP that was associated with a deeper tumor shrinkage. Undifferentiated tumors showed a consistently better OS, and PFS for SP versus XP, likely because cases without tumor shrinkage tended to be fewer for SP. Our data thus showed that SP was superior to XP in this setting, but there were qualitative differences in therapeutic efficacy dependent on tumor histology.
Pan-Cancer Analysis Identifies Tumor Cell Surface Targets for CAR-T Cell Therapies and Antibody Drug Conjugates
Authors: Li Xinhui , Zhou Jian , Zhang Weiwen , You Wenhua , Wang Jun , Zhou Linlin , Liu Lei , Chen Wei-Wei , Li Hanjie
Published: November 2022

Tumor cells can be recognized through tumor surface antigens by immune cells and antibodies, which therefore can be used as drug targets for chimeric antigen receptor-T (CAR-T) therapies and antibody drug conjugates (ADCs). In this study, we aimed to identify novel tumor-specific antigens as targets for more effective and safer CAR-T cell therapies and ADCs. Here, we performed differential expression analysis of pan-cancer data obtained from the Cancer Genome Atlas (TCGA), and then performed a series of conditional screenings including Cox regression analysis, Pearson correlation analysis, and risk-score calculation to find tumor-specific cell membrane genes. A tumor tissue-specific and highly expressed gene set containing 3919 genes from 17 cancer types was obtained. Moreover, the prognostic roles of these genes and the functions of these highly expressed membrane proteins were assessed. Notably, 427, 584, 431 and 578 genes were identified as risk factors for LIHC, KIRC, UCEC, and KIRP, respectively. Functional enrichment analysis indicated that these tumor-specific surface proteins might confer tumor cells the ability to invade and metastasize. Furthermore, correlation analysis displayed that most overexpressed membrane proteins were positively correlated to each other. In addition, 371 target membrane protein-coding genes were sifted out by excluding proteins expressed in normal tissues. Apart from the identification of well-validated genes such as GPC3, MSLN and EGFR in the literature, we further confirmed the differential protein expression of 23 proteins: ADD2, DEF6, DOK3, ENO2, FMNL1, MICALL2, PARVG, PSTPIP1, FERMT1, PLEK2, CD109, GNG4, MAPT, OSBPL3, PLXNA1, ROBO1, SLC16A3, SLC26A6, SRGAP2, and TMEM65 in four types of tumors. In summary, our findings reveal novel tumor-specific antigens, which could be potentially used for next-generation CAR-T cell therapies and ADC discovery.
Integrated Analysis of TME and Hypoxia Identifies a Classifier to Predict Prognosis and Therapeutic Biomarkers in Soft Tissue Sarcomas
Authors: Xu Ruiling , Qi Lin , Ren Xiaolei , Zhang Wenchao , Li Chenbei , Liu Zhongyue , Tu Chao , Li Zhihong
Published: November 2022

Soft tissue sarcoma (STS) is one of the rarest but most aggressive cancer. It is important to note that intratumoral hypoxia and tumor microenvironment (TME) infiltration play a significant role in the growth and therapeutic resistance of STS. The goal of this study was therefore to determine whether linking hypoxia-related parameters to TME cells could provide a more accurate prediction of prognosis and therapeutic response. An analysis of 109 hypoxia-related genes and 64 TME cells was conducted in STS. Hypoxia-TME classifier was constructed based on 6 hypoxia prognostic genes and 8 TME cells. As a result, we evaluated the prognosis, tumor, and immune characteristics, as well as the effectiveness of therapies in Hypoxia-TME-defined subgroups. The Lowplus group showed a better prognosis and therapeutic response than any other subgroup. It is possible to unravel these differences based on immune-related molecules and somatic mutations in tumors. Further validation of Hypoxia-TME was done in an additional cohort of 225 STS patients. Additionally, we identified five key genes through differential analysis and RT-qPCR, namely, ACSM5, WNT7B, CA9, MMP13, and RAC3, which could be targeted for therapy. As a whole, the Hypoxia-TME classifier demonstrated a pretreatment predictive value for prognosis and therapeutic outcome, providing new approaches to therapy strategizing for patients.
Endothelial-Specific Molecule 1 Inhibition Lessens Productive Angiogenesis and Tumor Metastasis to Overcome Bevacizumab Resistance
Authors: Kang Nannan , Liang Xue , Fan Buxi , Zhao Chen , Shen Beiyu , Ji Xuemei , Liu Yu
Published: November 2022

The development of drug resistance in malignant tumors leads to disease progression, creating a bottleneck in treatment. Bevacizumab is widely used clinically, and acts by inhibiting angiogenesis to “starve” tumors. Continuous treatment can readily induce rebound proliferation of tumor blood vessels, leading to drug resistance. Previously, we found that the fragment crystallizable (Fc) region of bevacizumab cooperates with the Toll-like receptor-4 (TLR4) ligand to induce M2b polarization in macrophages and secrete tumor necrosis factor-α (TNFα), which promotes immunosuppression, tumor metastasis, and angiogenesis. However, the downstream mechanism underlying TNFα-mediated bevacizumab resistance requires further investigation. Our RNA-Seq analysis results revealed that the expression of endothelial cell specific molecule-1 (ESM1) increased significantly in drug-resistant tumors and promoted metastasis and angiogenesis in vitro and in vivo. Furthermore, TNFα induced the upregulation of ESM1, which promotes metastasis and angiogenesis and regulates matrix metalloprotease-9 (MMP9), vascular endothelial growth factor (VEGF), and delta-like ligand-4 molecules (DLL4). Accordingly, the curative effect of bevacizumab improved by neutralizing ESM1 with high-affinity anti-ESM1 monoclonal antibody 1-2B7 in bevacizumab-resistant mice. This study provides important insights regarding the molecular mechanism by which TNFα-induced ESM1 expression promotes angiogenesis, which is significant for elucidating the mechanism of bevacizumab drug resistance and possibly identifying appropriate biosimilar molecules.
Plasticity in Classical Hodgkin Composite Lymphomas: A Systematic Review
Authors: Trecourt Alexis , Donzel Marie , Fontaine Juliette , Ghesquières Hervé , Jallade Laurent , Antherieu Gabriel , Laurent Camille , Mauduit Claire , Traverse-Glehen Alexsandra
Published: November 2022

The co-occurrence of several lymphomas in a patient defines composite/synchronous lymphoma. A common cellular origin has been reported for both contingents of such entities. In the present review, we aimed to gather the available data on composite lymphomas associating a classical Hodgkin lymphoma (cHL) with another lymphoma, to better understand the plasticity of mature B and T-cells. This review highlights that >70% of patients with a composite lymphoma are ≥55 years old, with a male predominance. The most reported associations are cHL with follicular lymphoma or diffuse large B-cell lymphoma, with over 130 cases reported. The cHL contingent is often of mixed cellularity type, with a more frequent focal/weak CD20 expression (30% to 55.6%) compared to de novo cHL, suggesting a particular pathophysiology. Moreover, Hodgkin cells may express specific markers of the associated lymphoma (e.g., BCL2/BCL6 for follicular lymphoma and Cyclin D1 for mantle cell lymphoma), sometimes combined with common BCL2/BCL6 or CCND1 rearrangements, respectively. In addition, both contingents may share similar IgH/IgK rearrangements and identical pathogenic variants, reinforcing the hypothesis of a common clonal origin. Finally, cHL appears to be endowed with a greater plasticity than previously thought, supporting a common clonal origin and a transdifferentiation process during lymphomagenesis of composite lymphomas.
Surgical Extent for Oral Cancer: Emphasis on a Cut-Off Value for the Resection Margin Status: A Narrative Literature Review
Authors: Jang Jeon Yeob , Choi Nayeon , Jeong Han-Sin
Published: November 2022

The optimal cut-off point of the resection margin was recently debated in oral cancer. To evaluate the current evidence of the dynamic criteria of the resection margin, a review of the available literature was performed. Studies were sourced from PubMed and EMBASE by searching for the keywords “mouth neoplasm”, “oral cancer”, “oral cavity cancer”, “oral squamous cell carcinoma”, “tongue cancer”, “margins of excision”, “surgical margin” and “resection margin”. We found approximately 998 articles on PubMed and 2227 articles on EMBASE. A total of 3225 articles was identified, and 2763 of those were left after removing the duplicates. By applying advanced filters about the relevance of the subjects, these were narrowed down to 111 articles. After the final exclusion, 42 full-text articles were reviewed. The universal cut-off criteria of 5 mm used for determining the resection margin status has been debated due to recent studies evaluating the impact of different margin criteria on patient prognosis. Of note, the degree of the microscopic extension from the gross tumor border correlates with tumor dimensions. Therefore, a relatively narrow safety margin can be justified in early-stage oral cancer without the additional risk of recurrence, while a wide safety margin might be required for advanced-stage oral cancer. This review suggests a surgical strategy to adjust the criteria for risk grouping and adjuvant treatments, according to individual tumor dimensions or characteristics. In the future, it might be possible to establish individual tumor-specific surgical margins and risk stratification during or after surgery. However, the results should be interpreted with caution because there is no strong evidence (e.g., prospective randomized controlled studies) yet to support the conclusions. Our study is meaningful in suggesting future research directions and discussions.
Review of Intraoperative Adjuncts for Maximal Safe Resection of Gliomas and Its Impact on Outcomes
Authors: Chanbour Hani , Chotai Silky
Published: November 2022

Maximal safe resection is the mainstay of treatment in the neurosurgical management of gliomas, and preserving functional integrity is linked to favorable outcomes. How these modalities differ in their effectiveness on the extent of resection (EOR), survival, and complications remains unknown. A systematic literature search was performed with the following inclusion criteria: published between 2005 and 2022, involving brain glioma surgery, and including one or a combination of intraoperative modalities: intraoperative magnetic resonance imaging (iMRI), awake/general anesthesia craniotomy mapping (AC/GA), fluorescence-guided imaging, or combined modalities. Of 525 articles, 464 were excluded and 61 articles were included, involving 5221 glioma patients, 7(11.4%) articles used iMRI, 21(36.8%) used cortical mapping, 15(24.5%) used 5-aminolevulinic acid (5-ALA) or fluorescein sodium, and 18(29.5%) used combined modalities. The heterogeneity in reporting the amount of surgical resection prevented further analysis. Progression-free survival/overall survival (PFS/OS) were reported in 18/61(29.5%) articles, while complications and permanent disability were reported in 38/61(62.2%) articles. The reviewed studies demonstrate that intraoperative adjuncts such as iMRI, AC/GA mapping, fluorescence-guided imaging, and a combination of these modalities improve EOR. However, PFS/OS were underreported. Combining multiple intraoperative modalities seems to have the highest effect compared to each adjunct alone.
Quinoline Derivatives with Different Functional Groups: Evaluation of Their Catecholase Activity
Authors: Moutaouakil Mohamed , Tighadouini Said , M. Almarhoon Zainab , I. Al-Zaben Maha , Ben Bacha Abir , H. Masand Vijay , Jamaleddine Jamal , Saddik Rafik
Published: November 2022

In this work, we are interested in finding new catalysts for catecholase, whose principle is based on the oxidation reaction of catechol to o-quinone. In this context, we have studied a series of seven quinoline-based compounds. The present work indicates that the complexes formed between seven selected quinoline compounds and the copper salts viz. Cu(OAc)2, CuSO4, Cu(NO3)2, and CuCl2 elicit catalytic activities for the oxidation of catechol to o-quinone. The complexes formed with the Cu(OAc)2 salt show a much higher catalytic activity than the others, whereas the Cu(NO3)2 and CuCl2 salts formed complexes with low catalytic activity. This study also shows that the oxidation rate depends on two factors, namely the chemical structure of the ligands and the nature of the ions coordinated with the copper.
Application of Dithiocarbamate Chitosan Modified SBA-15 for Catalytic Reductive Removal of Vanadium(V)
Authors: Huang Yilin , Wang Jia , Li Mengwei , You Zhixiong
Published: November 2022

We have successfully synthesized dithiocarbamate chitosan modified SBA-15 (CS2C@SBA) composites, with promise in vanadium (V(V)) elimination. Among the three composites using different mass ratios of dithiocarbamate chitosan to SBA-15, CS2C@SBA−3, which had the highest CS2 substitution, showed the best performance on V(V) removal of which the maximum adsorption capacity could achieve 218.00 mg/g at pH 3.0. The adsorption kinetics were best fitted with a pseudo−second order reaction model, suggesting a chemisorption mechanism. Meanwhile, the Langmuir model fitted better with the adsorption isotherm, revealing a monolayer adsorption behavior. Through FTIR and XPS analysis, the functional group −SH was identified as dominating reduction sites on this composite, which reduced 73.1% of V(V) into V(IV) and V(III). The functional group −NH− was the main adsorption site for vanadium species. This reaction followed a catalytic reduction coupled adsorption mechanism reducing most of V(V) into less toxic vanadium species. Furthermore, CS2C@SBA−3 showed great selectivity towards V(V) in the presence of various co−existing ions in synthetic wastewater and real water samples. Moreover, CS2C@SBA−3 could retain a removal efficiency over 90% after five adsorption−desorption cycles. Based on the aforementioned results, we can conclude that CS2C@SBA−3 has great potential to be applied in efficient remediation of vanadium water−pollution.
Novel Indium Vanadium Oxide Nanosheet-Supported Nickel Iron Oxide Nanoplate Heterostructure for Synergistically Enhanced Photocatalytic Degradation of Tetracycline
Authors: Sreeram N. , Aruna V. , Koutavarapu Ravindranadh , Lee Dong-Yeon , Shim Jaesool
Published: November 2022

Semiconductor-based heterogeneous photocatalytic oxidation processes have received considerable attention for the remediation of toxic pollutants. Herein, InVO4/NiFe2O4 nanocomposites were synthesized using a facile hydrothermal technique. Furthermore, various characterization results revealed the successful loading of NiFe2O4 nanoplates over InVO4 nanosheets, thereby signifying the formation of a heterostructure. The performance of the synthesized photocatalyst was tested for tetracycline (TC) antibiotic removal. The optimized InVO4/NiFe2O4 nanocomposite exhibits maximum photodegradation of TC molecules (96.68%) in 96 min; this is approximately 6.47 and 4.93 times higher than that observed when using NiFe2O4 and InVO4, respectively. The strong interaction between the InVO4 nanosheets and NiFe2O4 nanoplates can improve the visible-light absorption and hinder the recombination of charge carriers, further enhancing the photocatalytic performance. Moreover, hydroxyl radicals play a crucial role in the photodegradation of TC antibiotics.
A Stable and Reusable Supported Copper Catalyst for the Selective Liquid-Phase Hydrogenation of 5-Hydroxymethylfurfural to 2,5-Bis(hydroxymethyl)furan
Authors: Zelin Juan , Meyer Camilo Ignacio , Duarte Hernán Antonio , Marchi Alberto
Published: November 2022

Synthesis of 2,5-bis(hydroxymethyl)furan (BHMF) by selective 5-hydroxymethylfurfural (HMF) hydrogenation is ecofriendly and industrially important since HMF is obtained from renewable sources, and BHMF is a raw material used for production of biodegradable polymers. Four copper-based catalysts were prepared by incipient wetness impregnation (Cu/SiO2-I, Cu/Al2O3-I), precipitation–deposition (Cu/SiO2-PD) and coprecipitation (CuMgAl), and then tested in the liquid-phase hydrogenation of HMF. Metallic phases with large copper particles were obtained by incipient wetness impregnation, while precipitation methods gave highly dispersed metal copper nanoparticles. The pattern found for the concentration and strength of surface acid sites was: CuMgAl > Cu/Al2O3-I > Cu/SiO2-PD > Cu/SiO2-I. The copper-based catalysts active in HMF hydrogenation are all highly selective to BHMF, but the intrinsic activity and stability depend on metallic copper dispersion and support nature. The catalyst stability becomes poorer in the cases that the metallic phase is formed by large copper particles or interacts with high-acidity supports. Therefore, the catalyst with the highest activity, BHMF yield and stability was Cu/SiO2-PD. Furthermore, it was found that Cu/SiO2-PD is reusable in the selective liquid-phase HMF hydrogenation after being submitted to a two-step thermal treatment: (1) calcination under air flow at 673 K; (2) reduction under H2 flow at 523 K.
A Brønsted Acidic Deep Eutectic Solvent for N-Boc Deprotection
Authors: Procopio Debora , Siciliano Carlo , De Rose Roberta , Trombino Sonia , Cassano Roberta , Di Gioia Maria Luisa
Published: November 2022

The tert-butyloxycarbonyl (Boc) group is one of the most widely used amine-protecting groups in multistep reactions in synthetic organic chemistry as well as in peptide synthesis. Traditional methods to remove the Boc group have disadvantages in terms of high acidity, the use of expensive reagents, excessive amounts of catalysts and harmful solvents as well as high temperatures, making them environmentally unsustainable. Therefore, more efforts must be stepwise tightened to make Boc removal practical, clean, and minimize any potential impact. We describe an efficient and sustainable method for N-Boc deprotection by means of a choline chloride/p-toluenesulfonic acid deep eutectic solvent (DES), which is used as a reaction medium plus catalyst. The adopted conditions allow the deprotection of a wide variety of N-Boc derivatives in excellent yields. The strategy has found advantages in greening, simplicity, and short reaction times, resulting in a useful alternative to standard methods.
Exploring Deep Learning for Metalloporphyrins: Databases, Molecular Representations, and Model Architectures
Authors: Su An , Zhang Chengwei , She Yuan-Bin , Yang Yun-Fang
Published: November 2022

Metalloporphyrins have been studied as biomimetic catalysts for more than 120 years and have accumulated a large amount of data, which provides a solid foundation for deep learning to discover chemical trends and structure–function relationships. In this study, key components of deep learning of metalloporphyrins, including databases, molecular representations, and model architectures, were systematically investigated. A protocol to construct canonical SMILES for metalloporphyrins was proposed, which was then used to represent the two-dimensional structures of over 10,000 metalloporphyrins in an existing computational database. Subsequently, several state-of-the-art chemical deep learning models, including graph neural network-based models and natural language processing-based models, were employed to predict the energy gaps of metalloporphyrins. Two models showed satisfactory predictive performance (R2 0.94) with canonical SMILES as the only source of structural information. In addition, an unsupervised visualization algorithm was used to interpret the molecular features learned by the deep learning models.
Effects of Nitisinone on Oxidative and Inflammatory Markers in Alkaptonuria: Results from SONIA1 and SONIA2 Studies
Authors: Braconi Daniela , Geminiani Michela , Psarelli Eftychia Eirini , Giustarini Daniela , Marzocchi Barbara , Rossi Ranieri , Bernardini Giulia , Spiga Ottavia , Gallagher James A. , Le Quan Sang Kim-Hanh , Arnoux Jean-Baptiste , Imrich Richard , Al-Sbou Mohammed S. , Gornall Matthew , Jackson Richard , Ranganath Lakshminarayan R. , Santucci Annalisa
Published: November 2022

Nitisinone (NTBC) was recently approved to treat alkaptonuria (AKU), but there is no information on its impact on oxidative stress and inflammation, which are observed in AKU. Therefore, serum samples collected during the clinical studies SONIA1 (40 AKU patients) and SONIA2 (138 AKU patients) were tested for Serum Amyloid A (SAA), CRP and IL-8 by ELISA; Advanced Oxidation Protein Products (AOPP) by spectrophotometry; and protein carbonyls by Western blot. Our results show that NTBC had no significant effects on the tested markers except for a slight but statistically significant effect for NTBC, but not for the combination of time and NTBC, on SAA levels in SONIA2 patients. Notably, the majority of SONIA2 patients presented with SAA > 10 mg/L, and 30 patients in the control group (43.5%) and 40 patients (58.0%) in the NTBC-treated group showed persistently elevated SAA > 10 mg/L at each visit during SONIA2. Higher serum SAA correlated with lower quality of life and higher morbidity. Despite no quantitative differences in AOPP, the preliminary analysis of protein carbonyls highlighted patterns that deserve further investigation. Overall, our results suggest that NTBC cannot control the sub-clinical inflammation due to increased SAA observed in AKU, which is also a risk factor for developing secondary amyloidosis.
The Species of Gut Bacteria Associated with Antitumor Immunity in Cancer Therapy
Authors: Qi Xiaoqiang , Liu Yajun , Hussein Samira , Choi Grace , Kimchi Eric T. , Staveley-O’Carroll Kevin F. , Li Guangfu
Published: November 2022

Both preclinical and clinical studies have demonstrated that the modulation of gut microbiota could be a promising strategy for enhancing antitumor immune responses and reducing resistance to immunotherapy in cancer. Various mechanisms, including activation of pattern recognition receptors, gut commensals-produced metabolites and antigen mimicry, have been revealed. Different gut microbiota modulation strategies have been raised, such as fecal microbiota transplantation, probiotics, and dietary selection. However, the identification of gut bacteria species that are either favorable or unfavorable for cancer therapy remains a major challenge. Herein, we summarized the findings related to gut microbiota species observed in the modulation of antitumor immunity. We also discussed the different mechanisms underlying different gut bacteria’s functions and the potential applications of these bacteria to cancer immunotherapy in the future.
The Molecular Signature of Human Testicular Peritubular Cells Revealed by Single-Cell Analysis
Authors: Liebich Annika , Schmid Nina , Koupourtidou Christina , Herrmann Carola , Dietrich Kim-Gwendolyn , Welter Harald , Ninkovic Jovica , Mayerhofer Artur
Published: November 2022

Peritubular cells of the human testis form a small compartment surrounding the seminiferous tubules. They are crucial for sperm transport, and they emerge as contributors to the spermatogonial stem cell niche. They are among the least known cell types of the human body. We employed single-cell RNA sequencing of cultured human testicular peritubular cells (HTPCs), which had been isolated from testicular samples of donors with normal spermatogenesis. The significant overlap between our results and recently published ex vivo data indicates that HTPCs are a highly adequate cellular model to define and study these cells. Thus, based on the expression of several markers, HTPCs can be classified as testicular smooth muscle cells. Small differences between the in vivo/in vitro expressed genes may be due to cellular plasticity. Plasticity was also shown upon addition of FCS to the culture medium. Based on transcriptome similarities, four cellular states were identified. Further analyses confirmed the presence of known stem cell niche-relevant factors (e.g., GDNF) and identified unknown functions, e.g., the ability to produce retinoic acid. Therefore, HTPCs allow us to define the signature(s) and delineate the functions of human testicular peritubular cells. The data may also serve as a resource for future studies to better understand male (in)fertility.
Sex-Dependent Differences in Colorectal Cancer: With a Focus on Obesity
Authors: Wele Prachi , Wu Xian , Shi Haifei
Published: November 2022

Colorectal cancer (CRC) is the third most common cancer and has the second highest cancer-related mortality in the world. The incident rates of CRC vary country-wise; however, population studies and data from different countries show a general increase in the CRC rate in young adults, males, and females ≥65 years. CRC incidence is affected by age, sex, environmental, dietary, hormonal, and lifestyle factors. Obesity is a known disease that is spreading rapidly throughout the world. A large body of literature indicates that, among many conditions, obesity is the increasing cause of CRC. Even though obesity is one of the known factors for CRC development, limited studies are available that explain the mechanistic link between obesity, sex hormones, and CRC development. Thus, this review summarizes the literature and aims to understand sex-dependent differences in CRC, especially in the context of obesity.
Signaling Pathways Regulating Human Cervical Ripening in Preterm and Term Delivery
Authors: Socha Maciej W. , Flis Wojciech , Pietrus Miłosz , Wartęga Mateusz , Stankiewicz Martyna
Published: November 2022

At the end of gestation, the cervical tissue changes profoundly. As a result of these changes, the uterine cervix becomes soft and vulnerable to dilation. The process occurring in the cervical tissue can be described as cervical ripening. The ripening is a process derivative of enzymatic breakdown and inflammatory response. Therefore, it is apparent that cervical remodeling is a derivative of the reactions mediated by multiple factors such as hormones, prostaglandins, nitric oxide, and inflammatory cytokines. However, despite the research carried out over the years, the cellular pathways responsible for regulating this process are still poorly understood. A comprehensive understanding of the entire process of cervical ripening seems crucial in the context of labor induction. Greater knowledge could provide us with the means to help women who suffer from dysfunctional labor. The overall objective of this review is to present the current understanding of cervical ripening in terms of molecular regulation and cell signaling.
Trypanosoma cruzi DNA Polymerase β Is Phosphorylated In Vivo and In Vitro by Protein Kinase C (PKC) and Casein Kinase 2 (CK2)
Authors: Maldonado Edio , Rojas Diego A. , Urbina Fabiola , Valenzuela-Pérez Lucía , Castillo Christian , Solari Aldo
Published: November 2022

DNA polymerase β plays a fundamental role in the life cycle of Trypanosoma cruzi since it participates in the kinetoplast DNA repair and replication. This enzyme can be found in two forms in cell extracts of T. cruzi epimastigotes form. The H form is a phosphorylated form of DNA polymerase β, while the L form is not phosphorylated. The protein kinases which are able to in vivo phosphorylate DNA polymerase β have not been identified yet. In this work, we purified the H form of this DNA polymerase and identified the phosphorylation sites. DNA polymerase β is in vivo phosphorylated at several amino acid residues including Tyr35, Thr123, Thr137 and Ser286. Thr123 is phosphorylated by casein kinase 2 and Thr137 and Ser286 are phosphorylated by protein kinase C-like enzymes. Protein kinase C encoding genes were identified in T. cruzi, and those genes were cloned, expressed in bacteria and the recombinant protein was purified. It was found that T. cruzi possesses three different protein kinase C-like enzymes named TcPKC1, TcPKC2, and TcPKC3. Both TcPKC1 and TcPKC2 were able to in vitro phosphorylate recombinant DNA polymerase β, and in addition, TcPKC1 gets auto phosphorylated. Those proteins contain several regulatory domains at the N-terminus, which are predicted to bind phosphoinositols, and TcPKC1 contains a lipocalin domain at the C-terminus that might be able to bind free fatty acids. Tyr35 is phosphorylated by an unidentified protein kinase and considering that the T. cruzi genome does not contain Tyr kinase encoding genes, it is probable that Tyr35 could be phosphorylated by a dual protein kinase. Wee1 is a eukaryotic dual protein kinase involved in cell cycle regulation. We identified a Wee1 homolog in T. cruzi and the recombinant kinase was assayed using DNA polymerase β as a substrate. T. cruzi Wee1 was able to in vitro phosphorylate recombinant DNA polymerase β, although we were not able to demonstrate specific phosphorylation on Tyr35. Those results indicate that there exists a cell signaling pathway involving PKC-like kinases in T. cruzi.
Complex Oxide Nanoparticle Synthesis: Where to Begin to Do It Right?
Authors: Gager Elizabeth , Halbert William , Nino Juan C.
Published: November 2022

Synthesis of advanced ceramics requires a high degree of control over the particle size and stoichiometry of the material. When choosing a synthesis method for complex oxides it is important to begin with the correct precursors and solvents to achieve high purity nanoparticles. Here, we detail the selection process for precursors and solvents for liquid-phase precipitation synthesis. Data for metal nitrate, chloride, acetate, and oxalate precursors has been compiled to assist future synthesis. The role of hydration within the precursors is discussed as it affects the final stoichiometry of the material. Melting temperatures are also compiled for these compounds to assist in material selection. The solubility of the precursors in different solvents is examined to determine the correct solvent during synthesis. As an example, using the methodology presented here, two different materials are synthesized based on commonly available precursors. A catalyst based on a quaternary perovskite and an advanced ionic conductor based on a high entropy fluorite oxide are synthesized using precipitation methods and their characterization is detailed.
Screening of Chemical Composition, Antimicrobial and Antioxidant Activities of Essential Oil and Volatile Fraction from Olive Mill Wastewater
Authors: Ait Si Said Chahinez , Riad Nacera , Zahi Mohamed Reda , Sabour Smain , Akkal Salah , Zam Wissam , Touafek Ouassila , El Hattab Mohamed
Published: November 2022

Oil mill wastewater is the main by-product of the olive oil industry resulting mainly from the treatment and pressing of olives in mills. It is a rich source of nutrients and phytochemicals with a wide spectrum of biological properties. The present study focuses on the chemical analysis and evaluation of the antimicrobial and antioxidant activity of the essential oil (EO) and the volatile fraction (VF) obtained, respectively, by hydrodistillation. Chemical analysis by gas chromatography coupled to mass spectrometry (GC/MS) and a flame ionisation detector (GC/FID) revealed the predominance of phenolic compounds (25.71%, 60.36%) and fatty acids (62.37%, 38.25%) for the VF and EO, respectively. It was also shown that the main compounds were oleic acid (24.9%) for the VF and 4-ethylphenol (28.5%) for the EO. The results of the antimicrobial activity in terms of MIC values against twelve microorganisms showed that, overall, the VF was more active than the EO. The antioxidant activity of the VF and EO was evaluated using the DPPH assay and expressed as half-maximal inhibitory concentration (IC50), where the EO (218 μg/mL) showed better antioxidant activity than the VF (244 μg/mL). The results also revealed that the antimicrobial activity and antioxidant activity values for both oils were significantly lower than the standards used.
Mechanism of Fast NO Response in a WO3-Nanorod-Based Gas Sensor
Authors: Mineo Giacometta , Moulaee Kaveh , Neri Giovanni , Mirabella Salvo , Bruno Elena
Published: November 2022

The development of fast and reliable gas sensors is a pressing and growing problem for environmental monitoring due to the presence of pollutants in the atmosphere. Among all gases, particular attention is devoted to NO, which can cause serious health problems. WO3 nanorods represent promising candidates for this purpose due to their high electrical stability and low cost of production. Here, the hydrothermal synthesis of WO3 nanorods is reported, in addition to the realization of a chemo-resistive NO sensor. NO-sensing tests were performed at different temperatures (250–400 °C) and under different gas concentrations (250–2500 ppm), and NO response and recovery curves were also modeled by using the Langmuir adsorption theory by highlighting the NO-sensing mechanism of the WO3 nanorods. An interaction occurred at the surface between NO and the adsorbed oxygen ions, thus clarifying the NO-reducing behavior. The fast response and recovery times open the route for the development of fast NO sensors based on WO3.
Do Parents of Children with ADHD Know the Disease? Results from a Cross-Sectional Survey in Zhejiang, China
Authors: Fan Xiaoli , Ma Ye , Cai Jingjing , Zhu Guochun , Gao Weijia , Zhang Yanyi , Lin Nannan , Rao Yanxiao , Mao Shujiong , Li Rong , Yang Rongwang
Published: November 2022

Parents’ knowledge, attitudes, and beliefs about attention-deficit/hyperactivity disorder (ADHD) are crucial in the selection of the treatment strategy and how to care for children with ADHD. However, little is known about parents’ conception in mainland China. A semi-structured questionnaire was used to assess this information with 25 true/false questions regarding ADHD, and other questions investigating the methods of acquiring ADHD-related information, treatment preference, and concerns about ADHD treatment strategy. We found that the average score of all the participants was 17.42 ± 2.69 (total of 25 points) for the questionnaire on knowledge, attitudes, and beliefs about ADHD. This indicated that the parents had insufficient knowledge of this disease profile. They always accessed specialized information through mobile internet. For the treatment options, the investigated parents chose psychotherapy treatment rather than medications, in that they worried about the side effects of medication and expected to find alternative treatment strategies. The present investigation demonstrated that most parents lack knowledge about ADHD in treatment decision making in China. Medical professionals should provide parents with evidence-based ADHD-related information to help them understand this disease.
Tumor Molecular and Microenvironment Characteristics in EBV-Associated Malignancies as Potential Therapeutic Targets: Focus on Gastric Cancer
Authors: Atri-Schuller Aviva , Abushukair Hassan , Cavalcante Ludimila , Hentzen Stijn , Saeed Azhar , Saeed Anwaar
Published: November 2022

Although most people are infected with Epstein-Barr Virus (EBV) during their lifetime, only a minority of them develop an EBV-associated malignancy. EBV acts in both direct and indirect ways to transform infected cells into tumor cells. There are multiple ways in which the EBV, host, and tumor environment interact to promote malignant transformation. This paper focuses on some of the mechanisms that EBV uses to transform the tumor microenvironment (TME) of EBV-associated gastric cancer (EBVaGC) for its benefit, including overexpression of Indoleamine 2,3-Dioxygenase 1 (IDO1), synergism between H. pylori and EBV co-infection, and M1 to M2 switch. In this review, we expand on different modalities and combinatorial approaches to therapeutically target this mechanism.
Assessment of Proliferation and Apoptosis in Testes of Rats after Experimental Localized Electron Irradiation
Authors: Demyashkin Grigory , Koryakin Sergey , Moiseev Aleksandr , Saburov Vyatcheslav , Zatsepina Margarita , Epifanova Maya , Stepanova Yulia , Shchekin Vladimir , Vadyukhin Matvey , Shegay Petr , Kaprin Andrei
Published: November 2022

Background and purpose: With the emergence of linear accelerators in radiotherapy, it becomes necessary to accurately select new dosing regimens. The purpose of this study was to assess the morphological changes of spermatogenesis after radiation exposure. Materials and methods: Male Wistar rats (n = 40) were subjected to targeted ionizing radiation on a pulsed electron accelerator “NOVAC-11” with doses of 2, 8 and 12 Gy. Spermatogenesis was assessed a week later using light microscopy and immunohistochemical method (antibodies to Ki-67, Bcl-2, p53, Caspase 3). Results: A decrease in the number of normal germ cells was seen in all experimental groups, while radioresistant Sertoli and Leydig cells were barely affected. The most serious damage to the tubules and germ cells was observed in 8 and 12 Gy irradiation groups. IHC analysis of testes after irradiation showed a shift in the proliferative-apoptotic balance toward apoptosis of germ cells: a decrease in the expression levels of Ki-67 and Bcl-2, an increase in p53-positive and caspase 3-positive cells by the end of the experiment. Conclusion: Dose-dependent progressive pathomorphological changes in histoarchitectonics of the testes are traced, and a decrease in the number of germ cells is seen on the seventh day after irradiation with a pulsed electron accelerator “NOVAC-11”.
Early Drought Stress Warning in Plants: Color Pictures of Photosystem II Photochemistry
Authors: Moustakas Michael , Sperdouli Ilektra , Moustaka Julietta
Published: November 2022

Drought, the major limiting factor for plant growth and crop productivity, affecting several physiological and biochemical processes, is expected to increase in duration, intensity, and frequency as a consequence of climate change. Plants have developed several approaches to either avoid or tolerate water deficit. Plants as a response to drought stress (DS), close stomata, reducing carbon dioxide (CO2) entry in the leaf, thus decreasing photosynthesis which results in reduced synthesis of essential organic molecules that sustain the life on earth. The reduced CO2 fixation, decreases electron transport rate (ETR), while the absorbed light energy overdoes what can be used for photochemistry resulting in excess reactive oxygen species (ROS) and oxidative stress. Current imaging techniques allow non-destructive monitoring of changes in the physiological state of plants under DS. Thermographic visualization, near-infrared imaging, and chlorophyll a fluorescence imaging are the most common verified imaging techniques for detecting stress-related changes in the display of light emission from plant leaves. Chlorophyll a fluorescence analysis, by use of the pulse amplitude modulation (PAM) method, can principally calculate the amount of absorbed light energy that is directed for photochemistry in photosystem II (PSII) (ΦPSII), dissipated as heat (ΦNPQ), or dissipated by the non-radiative fluorescence processes (ΦNO). The method of chlorophyll a fluorescence imaging analysis by providing colour pictures of the whole leaf PSII photochemistry, can successfully identify the early drought stress warning signals. Its implementation allowed visualization of the leaf spatial photosynthetic heterogeneity and discrimination between mild drought stress (MiDS), moderate drought stress (MoDS), and severe drought stress (SDS). The fraction of open reaction centers of PSII (qp) is suggested as the most sensitive and suitable indicator of an early drought stress warning and also for selecting drought tolerant cultivars.
Mitigation of Climate Change for Urban Agriculture: Water Management of Culinary Herbs Grown in an Extensive Green Roof Environment
Authors: Walters Stuart Alan , Gajewski Christina , Sadeghpour Amir , Groninger John W.
Published: November 2022

Extensive green roofs provide space for local agriculture in dense urban environments. However, already extreme drought and heat conditions on green roofs are likely to worsen under future climates, challenging urban crop production and impeding food security. The potential productivity of annual and perennial culinary herbs on an extensive green roof (~8 cm depth) with minimal, but consistent, water inputs was evaluated within a humid, subtropical climate (Southern Illinois University-Carbondale, Carbondale, IL, USA). Vigor, growth, and overwintering ability of four different perennial culinary herbs, namely garlic chives (Allium tuberosum), lavender (Lavandula angustifolia ‘Munstead Dwarf’), lemon balm (Melissa officinalis), and winter thyme (Thymus vulgaris ‘Winter Thyme’), as well as vigor and growth of annual ‘Italian large-leaf’ basil (Ocimum basilicum) were evaluated under twice-weekly, weekly, and fortnightly water applications of 1 L to each plant. All species of perennial herbs produced greater dry perennial biomass and overwintering potential under the two most frequent water applications. Similarly, with weekly water applications, basil proved highly suitable for production in an extensive green roof environment. Weekly watering was required to provide commercially viable plant growth, vigor, and overwinter survival for all perennial herbs. These results indicate that supplemental water is an important consideration for sustaining culinary herb production on extensive green roofs with the increasingly hot and dry conditions provided under the climate change scenarios projected for cities currently experiencing temperate climates.
Assessing the Adaptive Capacity of Slum Households to Flooding in the Coastline of Portee and Rokupa, Freetown, Sierra Leone
Authors: Turay Bashiru
Published: November 2022

Frequent flooding has been a significant problem in Freetown, causing loss of lives and properties. The situation is worse for coastal residents, who are more vulnerable and exposed to the impacts. The government has made commitments to strengthen resilience and adaptive capacity by 2030. However, there is currently insufficient information to comprehend the coastal residents of Portee and Rokupa’s capacity to adapt to the yearly flooding to which they are subjected. This study aims to assess the adaptive capacity of 204 slum households selected by purposive sampling and using the local adaptive capacity framework. The results show that the widespread adaptive concerns are unflood-proofed housing; low membership in community-based organizations; and the lack of innovative, flexible and forward-looking flood management initiatives. This study argues that the inhabitants have reached their adaptation limit and are now fated to more loss and damage. The author recommends future studies to forecast the assets in the study location that will potentially be affected by different flood intensities when subjected to future climate change scenarios.
A Proposed Approach towards Quantifying the Resilience of Water Systems to the Potential Climate Change in the Lali Region, Southwest Iran
Authors: Zeydalinejad Nejat , Nassery Hamid Reza , Alijani Farshad , Shakiba Alireza , Ghazi Babak
Published: November 2022

Computing the resilience of water resources, especially groundwater, has hitherto presented difficulties. This study highlights the calculation of the resilience of water resources in the small-scale Lali region, southwest Iran, to potential climate change in the base (1961–1990) and future (2021–2050) time periods under two Representative Concentration Pathways, i.e., RCP4.5 and RCP8.5. The Lali region is eminently suitable for comparing the resilience of alluvial groundwater (Pali aquifer), karst groundwater (Bibitarkhoun spring and the observation wells W1, W2 and W3) and surface water (Taraz-Harkesh stream). The log-normal distribution of the mean annual groundwater level and discharge rate of the water resources was initially calculated. Subsequently, different conditions from extremely dry to extremely wet were assigned to the different years for every water system. Finally, the resilience values of the water systems were quantified as a number between zero and one, such that they can be explicitly compared. The Pali alluvial aquifer demonstrated the maximum resilience, i.e., 1, to the future climate change. The Taraz-Harkesh stream, which is fed by the alluvial aquifer and the Bibitarkhoun karst spring, which is the largest spring of the Lali region, depicted average resilience of 0.79 and 0.59, respectively. Regarding the karstic observation wells, W1 being located in the recharge zone had the lowest resilience (i.e., 0.52), W3 being located in the discharge zone had the most resilience (i.e., 1) and W2 being located between W1 and W3 had an intermediate resilience (i.e., 0.60) to future climate change.
Phosphorous Nanofertilizers for Precise Application in Rice Cultivation as an Adaptation to Climate Change
Authors: Saraiva Raquel , Ferreira Quirina , Rodrigues Gonçalo C. , Oliveira Margarida
Published: November 2022

Rice is the staple food of more than half of the world’s population, which is still growing. The great dependence that agriculture, and rice specially, has on fertilizers alongside extreme events that result from climatic change creates an urge for adaptation. Fertilizers are expensive, finite and a potential environmental problem. Their precise application, by the use of slow-release nanofertilizers, thus avoiding losses and consequently reducing the pressure on water resources, is one step forward in this adaptation. It can reduce costs and protect the environment while ensuring food production. Phosphorous is very important for rice, since it is involved in its flowering and root development, and its low availability to the plants constitutes a serious problem. The delivery of phosphorous through the crop cycle in the form of slow-release phosphorus nanofertilizer (Pnf) instead of the conventional annual bulk application reduces the amount of nutrients applied and increases the absorption by the crop. Combining the fertilizing effect with the use of natural stimulant compounds such as chitosan can protect the crop from diseases and increase its resilience to stress. The use of Pnf reduces the pressure on water resources and avoids imbalances in soil nutrients, thus responding to climatic change challenges and abiotic stresses.
Nanomaterials Applied in Coatings: Synthesis, Structures, Properties, and Applications
Authors: Shaikh Shoyebmohamad
Published: November 2022

Nanomaterials are an innovative class of materials in high demand for a wide range of practical uses [...]