bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimizing the Surrounding Building Configuration to Improve the Cooling Ability of Urban Parks on Surrounding Neighborhoods
Authors: Han Qian , Nan Xinge , Wang Han , Hu Yanjun , Bao Zhiyi , Yan Hai
Published: May 2023

Urban parks reduce air temperatures within parks and surroundings by exerting the cooling island effect, significant for mitigating the urban microclimate. However, the park cooling effect may be influenced by the surrounding building configuration, and this needs to be studied in more detail, in particular, to explore how to maximize the cooling effect of parks by adjusting the surrounding building configuration. Thus, in this study, the effects of building height, building interval, and building orientation on the cooling effect of a small urban park were investigated using field measurements and ENVI-met numerical simulations. The results demonstrated that (1) building height, building interval, and building orientation all impact the park cooling effect, but their impacts vary. (2) Building height had the strongest effect on the park cooling intensity, and adjusting building height provided the maximum park cooling intensity (1.2 °C). (3) Building orientation had the most effect on the park cooling distance, 100 m downwind of the park. (4) The park cooling effect is best when the surrounding buildings were parallel to the prevailing wind direction, and the park cool island has the greatest intensity and range. This study can guide decision-makers in optimizing building configuration to maximize the park cooling effect.
Dynamics and Determinants of Farmers’ Perceptions about Causes and Impacts of Climate Change on Agriculture in Saudi Arabia: Implications for Adaptation, Mitigation, and Sustainability
Authors: Alotaibi Bader Alhafi , Abbas Azhar , Ullah Raza , Azeem Muhammad Imran , Samie Abdus , Muddassir Muhammad , Dabiah Abduaziz Thabet , Raid Moodhi , Sadaf Tahira
Published: May 2023

Concerns over the potential harmful impacts of changing climate are strongly echoing around the globe. With its wide range of hazards to human societies, climate change is posing serious threats to human survival and impacting every aspect of human life, including food production systems. It is, therefore, imperative to gauge the local knowledge, perceptions, and adaptation capacity for the effective mitigation of the ill impacts of climate change. In this backdrop, the present study has been designed to investigate the perceptions of farmers regarding causes and impacts of climate change on agriculture. Required data were collected from the Madinah region in Saudi Arabia and analyzed to answer the following study questions: How do farmers perceive impacts of climate change? What factors affect their perceived impacts of climate change? Additionally, what factors affect their perception about the causes of climate change? Individual logit models were used to assess the impacts of various factors on perceived causes and perceived impacts of climate change on agriculture. A multinomial logit model was also employed to figure out significant determinants of perceived causes of climate change on agriculture. Results indicated that the most dominant perceived impacts of climate change are its effects on crop production, followed by drying water sources. The results also revealed that the age of the farmers had a positive effect on their perception of natural processes being the cause of climate change. Similarly, farming experience had an inverse effect on their perceptions regarding causes of climate change. The majority of the farmers seemed clear about the possible drivers of climate change in the country. In particular, about 79 percent of the farmers believed that GHGs and pollution are causing climate change in the country. The findings provide useful insights into farmers’ perceptions about causes and impacts of climate change and may be used by policymakers to strategically design extension and agricultural development initiatives for helping the farmers to implement sustainable agricultural practices to adapt to and lower the adverse impacts of climate change in the Kingdom.
Updates in Glioblastoma Immunotherapy: An Overview of the Current Clinical and Translational Scenario
Authors: Bianconi Andrea , Palmieri Giuseppe , Aruta Gelsomina , Monticelli Matteo , Zeppa Pietro , Tartara Fulvio , Melcarne Antonio , Garbossa Diego , Cofano Fabio
Published: May 2023

Glioblastoma (GBM) is the most common and aggressive central nervous system tumor, requiring multimodal management. Due to its malignant behavior and infiltrative growth pattern, GBM is one of the most difficult tumors to treat and gross total resection is still considered to be the first crucial step. The deep understanding of GBM microenvironment and the possibility of manipulating the patient’s innate and adaptive immune system to fight the neoplasm represent the base of immunotherapeutic strategies that currently express the future for the fight against GBM. Despite the immunotherapeutic approach having been successfully adopted in several solid and haematologic neoplasms, immune resistance and the immunosuppressive environment make the use of these strategies challenging in GBM treatment. We describe the most recent updates regarding new therapeutic strategies that target the immune system, immune checkpoint inhibitors, chimeric antigen receptor T cell therapy, peptide and oncolytic vaccines, and the relevant mechanism of immune resistance. However, no significant results have yet been obtained in studies targeting single molecules/pathways. The future direction of GBM therapy will include a combined approach that, in contrast to the inescapable current treatment modality of maximal resection followed by chemo- and radiotherapy, may combine a multifaceted immunotherapy treatment with the dual goals of directly killing tumor cells and activating the innate and adaptive immune response.
Cell-Free Supernatant Derived from a Lactobacillus casei BL23 Culture Modifies the Antiviral and Immunomodulatory Capacity of Mesenchymal Stromal Cells
Authors: Muzsai Szabolcs , Maryanovsky Ore-Matan , Ander Roland , Koncz Gábor , Mázló Anett , Bácsi Attila , Tóth Márta
Published: May 2023

Immune responses are highly complex and intricately regulated processes involving immune and non-immune cells in close direct and indirect contact with each other. These cells are highly sensitive to environmental signals, including factors derived from microbiota. Here, we demonstrate that the human microbiota member Lactobacillus casei (L. casei)-derived cell-free supernatant (CFS) enhances the sensitivity of mesenchymal-stromal-cell-like (MSCI) cells to viral stimuli and induces the development of dendritic cells (DCs) with anti-inflammatory and antiviral properties via pretreated MSCl cells. Our results showed that the production of INFβ and CXCL10 by MSCl cells upon viral stimulation was dependent on the presence of L. casei-derived extracellular vesicles in CFS during pretreatment. Moreover, L. casei CFS and/or poly (I:C)-conditioned MSCI cells altered the differentiation process of freshly isolated monocytes, as well as the developing DCs’ phenotype and functional activities, such as cytokine and chemokine secretion. Taken together, L. casei CFS contains factors which contribute to the pronounced antiviral response of MSCI cells, avoiding the development of inflammation via the induction of differentiation of anti-inflammatory DCs that retain their antiviral properties.
Decomposition of Small Molecules for Fragment-Based Drug Design
Authors: Ivanov Nikita N. , Shulga Dmitry A. , Palyulin Vladimir A.
Published: May 2023

In the drug design process, a frequent task is the decomposition of small molecules into fragments. There exist a number of approaches and methods to break molecules into fragments. However, a method that allows the decomposition of molecules into non-overlapping fragments that is meaningful in terms of medicinal chemistry is absent, and in this work, we present a new simple approach for the decomposition of molecules—MedChemFrag. It aims to break drug-like molecules into a set of rings and linkers, which are close to the perception of “fragments” by medicinal chemists. In contrast to most previous efforts aimed at breaking molecules using retrosynthetic feasible rules, our approach strives to preserve the functional groups, which may reveal the specific interaction pattern, e.g., the amide groups.
One Single Tube Reaction of Aptasensor-Based Magnetic Sensing System for Selective Fluorescent Detection of VEGF in Plasma
Authors: Kou Hwang-Shang , Lo Shao-Tsung , Wang Chun-Chi
Published: May 2023

In this study, a simple, easy and convenient fluorescent sensing system for the detection of the vascular endothelial growth factor (VEGF) based on VEGF aptamers, aptamer-complementary fluorescence-labeled probe and streptavidin magnetic beads was developed in one single tube. The VEGF is the most important biomarker in cancer, and it is investigated that the serum VEGF level varied according to the different types and courses of cancers. Hence, efficient quantification of VEGF is able to improve the accuracy of cancer diagnoses and the precision of disease surveillance. In this research, the VEGF aptamer was designed to be able to bind with the VEGF by forming G-quadruplex secondary structures; then, the magnetic beads would capture the non-binding aptamers due to non-steric interference; and finally, the fluorescence-labeled probes were hybridized with the aptamers captured by the magnetic beads. Therefore, the fluorescent intensity in the supernatant would specifically reflect the present VEGF. After an overall optimization, the optimal conditions for the detection of VEGF were as followed, KCl, 50 μM; pH 7.0; aptamer, 0.1 μM; and magnetic beads, 10 μL (4 μg/μL). The VEGF could be well quantified within a range of 0.2-2.0 ng/mL in plasma, and the calibration curve possessed a good linearity (y = 1.0391x + 0.5471, r = 0.998). The detection limit (LOD) was calculated to be 0.0445 ng/mL according to the formula (LOD = 3.3 × σ/S). The specificity of this method was also investigated under the appearance of many other serum proteins, and the data showed good specificity in this aptasensor-based magnetic sensing system. This strategy provided a simple, sensitive and selective biosensing platform for the detection of serum VEGF. Finally, it was expected that this detection technique can be used to promote more clinical applications.
Reversed Mirror Therapy (REMIT) after Stroke—A Proof-of-Concept Study
Authors: Tesio Luigi , Caronni Antonio , Russo Cristina , Felisari Giorgio , Banco Elisabetta , Simone Anna , Scarano Stefano , Bolognini Nadia
Published: May 2023

In mirror training (MIT), stroke patients strive to move their hands while looking at the reflected image of the unaffected one. The recruitment of the mirror neurons and visual-proprioceptive conflict are expected to facilitate the paretic voluntary movement. Here, a reversed MIT (REMIT) is presented, which requires moving hands while looking at the reflected image of the paretic one, giving the illusion of being unable to move the unimpaired hand. This study compares MIT and REMIT on post-stroke upper-limb recovery to gain clues on the mechanism of action of mirror therapies. Eight chronic stroke patients underwent two weeks of MIT and REMIT (five sessions each) in a crossover design. Upper-limb Fugl-Meyer, Box and Block and handgrip strength tests were administered at baseline and treatments end. The strength of the mirror illusion was evaluated after each session. MIT induced a larger illusory effect. The Fugl-Meyer score improved to the same extent after both treatments. No changes occurred in the Box and Block and the handgrip tests. REMIT and MIT were equally effective on upper-limb dexterity, challenging the exclusive role of mirror neurons. Contrasting learned nonuse through an intersensory conflict might provide the rationale for both forms of mirror-based rehabilitation after stroke.
A Comprehensive Transcriptional Signature in Pancreatic Ductal Adenocarcinoma Reveals New Insights into the Immune and Desmoplastic Microenvironments
Authors: Pérez-Díez Irene , Andreu Zoraida , Hidalgo Marta R. , Perpiñá-Clérigues Carla , Fantín Lucía , Fernandez-Serra Antonio , de la Iglesia-Vaya María , Lopez-Guerrero José A. , García-García Francisco
Published: May 2023

Pancreatic ductal adenocarcinoma (PDAC) prognoses and treatment responses remain devastatingly poor due partly to the highly heterogeneous, aggressive, and immunosuppressive nature of this tumor type. The intricate relationship between the stroma, inflammation, and immunity remains vaguely understood in the PDAC microenvironment. Here, we performed a meta-analysis of stroma-, and immune-related gene expression in the PDAC microenvironment to improve disease prognosis and therapeutic development. We selected 21 PDAC studies from the Gene Expression Omnibus and ArrayExpress databases, including 922 samples (320 controls and 602 cases). Differential gene enrichment analysis identified 1153 significant dysregulated genes in PDAC patients that contribute to a desmoplastic stroma and an immunosuppressive environment (the hallmarks of PDAC tumors). The results highlighted two gene signatures related to the immune and stromal environments that cluster PDAC patients into high- and low-risk groups, impacting patients’ stratification and therapeutic decision making. Moreover, HCP5, SLFN13, IRF9, IFIT2, and IFI35 immune genes are related to the prognosis of PDAC patients for the first time.
Crosstalk between ILC3s and Microbiota: Implications for Colon Cancer Development and Treatment with Immune Check Point Inhibitors
Authors: Drommi Fabiana , Calabrò Alessia , Vento Grazia , Pezzino Gaetana , Cavaliere Riccardo , Omero Fausto , Muscolino Paola , Granata Barbara , D’Anna Federica , Silvestris Nicola , De Pasquale Claudia , Ferlazzo Guido , Campana Stefania
Published: May 2023

Type 3 innate lymphoid cells (ILC3s) are primarily tissue-resident cells strategically localized at the intestinal barrier that exhibit the fast-acting responsiveness of classic innate immune cells. Populations of these lymphocytes depend on the transcription factor RAR-related orphan receptor and play a key role in maintaining intestinal homeostasis, keeping host–microbial mutualism in check. Current evidence has indicated a bidirectional relationship between microbiota and ILC3s. While ILC3 function and maintenance in the gut are influenced by commensal microbiota, ILC3s themselves can control immune responses to intestinal microbiota by providing host defense against extracellular bacteria, helping to maintain a diverse microbiota and inducing immune tolerance for commensal bacteria. Thus, ILC3s have been linked to host–microbiota interactions and the loss of their normal activity promotes dysbiosis, chronic inflammation and colon cancer. Furthermore, recent evidence has suggested that a healthy dialog between ILC3s and gut microbes is necessary to support antitumor immunity and response to immune checkpoint inhibitor (ICI) therapy. In this review, we summarize the functional interactions occurring between microbiota and ILC3s in homeostasis, providing an overview of the molecular mechanisms orchestrating these interactions. We focus on how alterations in this interplay promote gut inflammation, colorectal cancer and resistance to therapies with immune check point inhibitors.
Tumor-Infiltrating Lymphocytes and PD-L1 Expression in Pleomorphic Lobular Breast Carcinoma
Authors: Göker Menekse , Deblaere Stephanie , Denys Hannelore , Vergauwen Glenn , Naert Eline , Veldeman Liv , Monten Chris , Van den Broecke Rudy , Van Dorpe Jo , Braems Geert , Van de Vijver Koen
Published: May 2023

Background: The prognostic and predictive role of stromal tumor-infiltrating lymphocytes (sTILs) is undetermined in pleomorphic invasive lobular cancer (pILC). The same applies for the expression of PD-1/PD-L1 in this rare breast cancer subtype. Here, we aimed to investigate the expression of sTILs and analyze the PD-L1 expression levels in pILC. Methods: Archival tissues from sixty-six patients with pILC were collected. The sTIL density was scored as a percentage of tumor area using the following cut-offs: 0%; <5%; 5–9%; and 10–50%. The PD-L1 expression was analyzed using IHC on formalin-fixed, paraffin-embedded tissue sections using SP142 and 22C3 antibodies. Results: A total of 82% of the sixty-six patients were hormone receptor positive and 8% of cases were triple negative (TN), while 10% showed human epidermal growth factor receptor 2 (HER2) amplification. sTILs (≥1%) were present in 64% of the study population. Using the SP142 antibody, 36% of tumors demonstrated a positive PD-L1 score of ≥1%, and using the 22C3 antibody, 28% had a positive PD-L1 score of ≥1. There was no correlation between sTILs or PD-L1 expression and tumor size, tumor grade, nodal status, expression of estrogen receptor (ER), or amplification of HER2. Our data did not show any difference in survival between the three molecular subtypes of pILC with respect to sTILs and PD-L1 expression. Conclusion: This study shows that pILCs show some degree of sTILs and PD-L1 expression; however, this was not associated with a survival improvement. Additional large trials are needed to understand immune infiltration in lobular cancer, especially in the pleomorphic subtype.
RBM38 Reverses Sorafenib Resistance in Hepatocellular Carcinoma Cells by Combining and Promoting lncRNA-GAS5
Authors: Gao Xing , Lu Cheng , Liu Ziyu , Lin Yan , Huang Julu , Lu Lu , Li Shuanghang , Huang Xi , Tang Minchao , Huang Shilin , He Ziqin , She Xiaomin , Liang Rong , Ye Jiazhou
Published: May 2023

Background: Hepatocellular carcinoma (HCC) is a life-threatening human malignancy and the fourth leading cause of cancer-related deaths worldwide. Patients with HCC are often diagnosed at an advanced stage with a poor prognosis. Sorafenib is a multikinase inhibitor used as the first-line treatment for patients with advanced HCC. However, acquired resistance to sorafenib in HCC leads to tumor aggression and limits the drug’s survival benefits; the underlying molecular mechanisms for this resistance remain unclear. Methods: This study aimed to examine the role of the tumor suppressor RBM38 in HCC, and its potential to reverse sorafenib resistance. In addition, the molecular mechanisms underlying the binding of RBM38 and the lncRNA GAS5 were examined. The potential involvement of RBM38 in sorafenib resistance was examined using both in vitro and in vivo models. Functional assays were performed to assess whether RBM38: binds to and promotes the stability of the lncRNA GAS5; reverses the resistance of HCC to sorafenib in vitro; and suppresses the tumorigenicity of sorafenib-resistant HCC cells in vivo. Results: RBM38 expression was lower in HCC cells. The IC50 value of sorafenib was significantly lower in cells with RBM38 overexpression than in control cells. RBM38 overexpression improved sorafenib sensitivity in ectopic transplanted tumors and suppressed the growth rate of tumor cells. RBM38 could bind to and stabilize GAS5 in sorafenib-resistant HCC cells. In addition, functional assays revealed that RBM38 reversed sorafenib resistance both in vivo and in vitro in a GAS5-dependent manner. Conclusions: RBM38 is a novel therapeutic target that can reverse sorafenib resistance in HCC by combining and promoting the lncRNA GAS5.
Exploring Connections between Oral Microbiota, Short-Chain Fatty Acids, and Specific Cancer Types: A Study of Oral Cancer, Head and Neck Cancer, Pancreatic Cancer, and Gastric Cancer
Authors: Nouri Zahra , Choi Sung Weon , Choi Il Ju , Ryu Keun Won , Woo Sang Myung , Park Sang-Jae , Lee Woo Jin , Choi Wonyoung , Jung Yuh-Seog , Myung Seung-Kwon , Lee Jong-Ho , Park Joo-Yong , Praveen Zeba , Woo Yun Jung , Park Jin Hee , Kim Mi Kyung
Published: May 2023

The association between oral microbiota and cancer development has been a topic of intense research in recent years, with compelling evidence suggesting that the oral microbiome may play a significant role in cancer initiation and progression. However, the causal connections between the two remain a subject of debate, and the underlying mechanisms are not fully understood. In this case–control study, we aimed to identify common oral microbiota associated with several cancer types and investigate the potential mechanisms that may trigger immune responses and initiate cancer upon cytokine secretion. Saliva and blood samples were collected from 309 adult cancer patients and 745 healthy controls to analyze the oral microbiome and the mechanisms involved in cancer initiation. Machine learning techniques revealed that six bacterial genera were associated with cancer. The abundance of Leuconostoc, Streptococcus, Abiotrophia, and Prevotella was reduced in the cancer group, while abundance of Haemophilus and Neisseria enhanced. G protein-coupled receptor kinase, H+-transporting ATPase, and futalosine hydrolase were found significantly enriched in the cancer group. Total short-chain fatty acid (SCFAs) concentrations and free fatty acid receptor 2 (FFAR2) expression levels were greater in the control group when compared with the cancer group, while serum tumor necrosis factor alpha induced protein 8 (TNFAIP8), interleukin-6 (IL6), and signal transducer and activator of transcription 3 (STAT3) levels were higher in the cancer group when compared with the control group. These results suggested that the alterations in the composition of oral microbiota can contribute to a reduction in SCFAs and FFAR2 expression that may initiate an inflammatory response through the upregulation of TNFAIP8 and the IL-6/STAT3 pathway, which could ultimately increase the risk of cancer onset.
Emerging Targeted Therapies in Advanced Non-Small-Cell Lung Cancer
Authors: Li Shenduo , de Camargo Correia Guilherme Sacchi , Wang Jing , Manochakian Rami , Zhao Yujie , Lou Yanyan
Published: May 2023

Lung cancer remains the leading cause of cancer-related mortality worldwide. Non-small-cell lung cancer (NSCLC) is the most common type and is still incurable for most patients at the advanced stage. Targeted therapy is an effective treatment that has significantly improved survival in NSCLC patients with actionable mutations. However, therapy resistance occurs widely among patients leading to disease progression. In addition, many oncogenic driver mutations in NSCLC still lack targeted agents. New drugs are being developed and tested in clinical trials to overcome these challenges. This review aims to summarize emerging targeted therapy that have been conducted or initiated through first-in-human clinical trials in the past year.
The Effect of Induction Chemotherapy with VEGF Inhibition on Tumor Response in Synchronously Metastasized Potentially Resectable Colorectal Cancer
Authors: Thonhauser Rebecca , Poglitsch Marcus , Jonas Jan Philipp , Dong Yawen , Tschögl Madita , Gramberger Mariel , Salem Mohamed , Santol Jonas , Brandl Irmgard , Klimpfinger Martin , Vierziger Constantin , Gruenberger Thomas
Published: May 2023

(1) Background: The pathological tumor response of the primary tumor to induction chemotherapy in synchronously metastasized colorectal cancer (mCRC) patients has not been investigated. The aim of this study was to compare patients treated with induction chemotherapy combined with vascular endothelial growth factor (VEGF) or with epidermal growth factor receptor (EGFR) antibodies. (2) Methods: We present a retrospective analysis, where we included 60 consecutive patients with potentially resectable synchronous mCRC who received induction chemotherapy combined with either VEGF or EGFR antibodies. The primary endpoint of this study was the regression of the primary tumor, which was assessed by the application of the histological regression score according to Rödel. The secondary endpoints were recurrence-free survival (RFS) and overall survival (OS). (3) Results: A significantly better pathological response and a longer RFS for patients treated with the VEGF antibody therapy compared to those treated with the EGFR antibodies was demonstrated (p = 0.005 for the primary tumor and log-rank = 0.047 for RFS). The overall survival did not differ. The trial was registered with clinicaltrial.gov, number NCT05172635. (4) Conclusion: Induction chemotherapy combined with a VEGF antibody revealed a better pathological response of the primary tumor, leading to a better RFS compared to that with EGFR therapy; this has clinical relevance in patients with potentially resectable synchronously mCRC.
Extracellular Vesicles Derived from Human Umbilical Cord Mesenchymal Stromal Cells as an Efficient Nanocarrier to Deliver siRNA or Drug to Pancreatic Cancer Cells
Authors: Draguet Florian , Dubois Nathan , Bouland Cyril , Pieters Karlien , Bron Dominique , Meuleman Nathalie , Stamatopoulos Basile , Lagneaux Laurence
Published: May 2023

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers worldwide. Treatment of PDAC remains a major challenge. This study aims to evaluate, in vitro, the use of human umbilical cord mesenchymal stromal cell (UC-MSC)-derived EVs to specifically target pancreatic cancer cells. EVs were isolated from the FBS-free supernatants of the cultured UC-MSCs by ultracentrifugation and characterized by several methods. EVs were loaded with scramble or KRASG12D-targeting siRNA by electroporation. The effects of control and loaded EVs on different cell types were evaluated by assessing cell proliferation, viability, apoptosis and migration. Later, the ability of EVs to function as a drug delivery system for doxorubicin (DOXO), a chemotherapeutic drug, was also evaluated. Loaded EVs exhibited different kinetic rates of uptake by three cell lines, namely, BxPC-3 cells (pancreatic cancer cell line expressing KRASwt), LS180 cells (colorectal cell line expressing KRASG12D) and PANC-1 cells (pancreatic cell line expressing KRASG12D). A significant decrease in the relative expression of the KRASG12D gene after incubation with KRAS siRNA EVs was observed by real-time PCR. KRASG12D siRNA EVs significantly reduced the proliferation, viability and migration of the KRASG12D cell lines compared to scramble siRNA EVs. An endogenous EV production method was applied to obtain DOXO-loaded EVs. Briefly, UC-MSCs were treated with DOXO. After 24 h, UC-MSCs released DOXO-loaded EVs. DOXO-loaded EVs were rapidly taken up by PANC-1 cells and induced apoptotic cell death more efficiently than free DOXO. In conclusion, the use of UC-MSC-derived EVs as a drug delivery system for siRNAs or drugs could be a promising approach for the targeted treatment of PDAC.
Ready for Prime Time? Dendritic Cells in High-Grade Gliomas
Authors: Conarroe Claire A. , Bullock Timothy N. J.
Published: May 2023

High-grade gliomas are malignant brain tumors, and patient outcomes remain dismal despite the emergence of immunotherapies aimed at promoting tumor elimination by the immune system. A robust antitumor immune response requires the presentation of tumor antigens by dendritic cells (DC) to prime cytolytic T cells. However, there is a paucity of research on dendritic cell activity in the context of high-grade gliomas. As such, this review covers what is known about the role of DC in the CNS, DC infiltration of high-grade gliomas, tumor antigen drainage, the immunogenicity of DC activity, and DC subsets involved in the antitumor immune response. Finally, we consider the implications of suboptimal DC function in the context of immunotherapies and identify opportunities to optimize immunotherapies to treat high-grade gliomas.
HIF-1-Induced hsa-miR-429: Understanding Its Direct Targets as the Key to Developing Cancer Diagnostics and Therapies
Authors: Bartoszewska Sylwia , Sławski Jakub , Collawn James F. , Bartoszewski Rafal
Published: May 2023

MicroRNAs (miRNAs) play a critical role in the regulation of mRNA stability and translation. In spite of our present knowledge on the mechanisms of mRNA regulation by miRNAs, the utilization and translation of these ncRNAs into clinical applications have been problematic. Using hsa-miR-429 as an example, we discuss the limitations encountered in the development of efficient miRNA-related therapies and diagnostic approaches. The miR-200 family members, which include hsa-miR-429, have been shown to be dysregulated in different types of cancer. Although these miR-200 family members have been shown to function in suppressing epithelial-to-mesenchymal transition, tumor metastasis, and chemoresistance, the experimental results have often been contradictory. These complications involve not only the complex networks involving these noncoding RNAs, but also the problem of identifying false positives. To overcome these limitations, a more comprehensive research strategy is needed to increase our understanding of the mechanisms underlying their biological role in mRNA regulation. Here, we provide a literature analysis of the verified hsa-miR-429 targets in various human research models. A meta-analysis of this work is presented to provide better insights into the role of hsa-miR-429 in cancer diagnosis and any potential therapeutic approach.
Highlights on the General Preference for Multi-Over Mono-Coupling in the Suzuki–Miyaura Reaction
Authors: Lima Carlos F. R. A. C. , Lima Marco A. L. , Pinto J. Ricardo M. , Ribeiro M. Gabriela T. C. , Silva Artur M. S. , Santos Luís M. N. B. F.
Published: May 2023

A systematic synthetic study was performed to explain the usual trend in selectivity towards multi-coupling, over mono-coupling, in Suzuki–Miyaura reactions. This preference was observed under different reaction conditions: for various halobenzenes, using substituents on the boronic acid, and changing the catalyst and temperature. Moreover, this reaction selectivity was found to increase for more reactive systems towards oxidative addition and more diluted media. The results constitute experimental evidence that the formation of the totally substituted coupling product is kinetically favoured by a reaction path location—the proximity between the regenerated catalyst and the newly formed coupling intermediate promotes the subsequent reaction.
Multitasking Proteins and Their Involvement in Pathogenesis
Authors: Gizak Agnieszka
Published: May 2023

The “one protein, one function” paradigm, similar to the “one gene, one enzyme” hypothesis that dominated our thinking for a long time, has proven to be too simplistic [...]
Astrocyte Signature in Alzheimer’s Disease Continuum through a Multi-PET Tracer Imaging Perspective
Authors: Fontana Igor C. , Scarpa Miriam , Malarte Mona-Lisa , Rocha Filipa M. , Ausellé-Bosch Sira , Bluma Marina , Bucci Marco , Chiotis Konstantinos , Kumar Amit , Nordberg Agneta
Published: May 2023

Reactive astrogliosis is an early event in the continuum of Alzheimer’s disease (AD). Current advances in positron emission tomography (PET) imaging provide ways of assessing reactive astrogliosis in the living brain. In this review, we revisit clinical PET imaging and in vitro findings using the multi-tracer approach, and point out that reactive astrogliosis precedes the deposition of Aβ plaques, tau pathology, and neurodegeneration in AD. Furthermore, considering the current view of reactive astrogliosis heterogeneity—more than one subtype of astrocyte involved—in AD, we discuss how astrocytic body fluid biomarkers might fit into trajectories different from that of astrocytic PET imaging. Future research focusing on the development of innovative astrocytic PET radiotracers and fluid biomarkers may provide further insights into the heterogeneity of reactive astrogliosis and improve the detection of AD in its early stages.
Study of the Mechanisms of Polymorphic Transformations in Zirconium Dioxide upon Doping with Magnesium Oxide, as Well as Establishing the Relationship between Structural Changes and Strength Properties
Authors: Kurakhmedov Alisher E. , Morzabayev Aidar K. , Tleubay Islam , Berguzinov Askhat , Kozlovskiy Artem L.
Published: May 2023

The aim of this work is to study the mechanisms of polymorphic transformations in ZrO2 ceramics doped with MgO with different concentrations during thermal isochronous annealing, as well as the effect of the phase composition of ceramics on the change in strength properties and resistance to mechanical stress. Solving the problem of polymorphic transformations in zirconium dioxide by doping them with MgO will increase the resistance of ceramics to external influences, as well as increase the mechanical strength of ceramics. According to the data of X-ray phase analysis, it was found that the addition of the MgO dopant to the composition of ceramics at the chosen thermal annealing temperature leads to the initialization of polymorphic transformation processes, while changing the dopant concentration leads to significant differences in the types of polymorphic transformations. In the case of an undoped ZrO2 ceramic sample, thermal annealing at a temperature of 1500 °C leads to structural ordering due to the partial removal of deformation distortions of the crystal lattice caused by mechanochemical grinding. During the study of the effect of MgO doping and polymorphic transformations in ZrO2 ceramics on the strength properties, it was found that the main hardening effect is due to a change in the dislocation density during the formation of a ZrO2/MgO type structure. At the same time, polymorphic transformations of the m—ZrO2 → t—ZrO2 type have a greater effect on hardening at low dopant concentrations than t—ZrO2 → c—ZrO2 type transformations.
UIO-66/Ag/TiO2 Nanocomposites as Highly Active SERS Substrates for Quantitative Detection of Hexavalent Chromium
Authors: Ben Zixiang , Ma Guangran , Xu Fugang
Published: May 2023

Sensitive determination of Cr(VI) is of great importance as this is one of the most toxic heavy metal ions in the environment. In this work, a metal–organic framework (MOF) material, UIO-66 (University of Oslo, UIO), was introduced for the first time to develop a composite substrate, UIO-66/Ag/TiO2, for the sensitive SERS detection of Cr(VI) in water. The composition, morphology, crystal structure and optical property of the UIO-66/Ag/TiO2 were characterized by SEM, XRD, EDX, UV-Vis and Raman spectroscopy. The control experiment revealed the introduction of UIO-66 and TiO2 can improve the adsorption to Cr ions and thus greatly enhance the SERS signal of Cr(VI) on this composite substrate. The SERS signal can also be tuned by changing the dosage of TiO2. Under optimized conditions, UIO-66/Ag/TiO2 was used to detect Cr(VI) in water with different concentrations, which showed high sensitivity and good stability. The SERS signals showed a linear increase as the concentration of Cr(VI) increases from 5 × 10−9 M to 5 × 10−6 M. The detection limit was 5 nM, which was lower than the safe drinking water standard of the US Environmental Protection Agency (1 μM). Detection of Cr(VI) in the range of 1 × 10−7 M to 5 × 10−6 M in real lake water was also achieved. These results demonstrate the great potential of UIO-66/Ag/TiO2 composites as SERS substrates for the trace determination of Cr(VI) in the environmental field.
TMEM211 Promotes Tumor Progression and Metastasis in Colon Cancer
Authors: Chang Yung-Fu , Wang Hsing-Hsang , Shu Chih-Wen , Tsai Wei-Lun , Lee Cheng-Hsin , Chen Chun-Lin , Liu Pei-Feng
Published: May 2023

Colon cancer is the third most important cancer type, leading to a remarkable number of deaths, indicating the necessity of new biomarkers and therapeutic targets for colon cancer patients. Several transmembrane proteins (TMEMs) are associated with tumor progression and cancer malignancy. However, the clinical significance and biological roles of TMEM211 in cancer, especially in colon cancer, are still unknown. In this study, we found that TMEM211 was highly expressed in tumor tissues and the increased TMEM211 was associated with poor prognosis in colon cancer patients from The Cancer Genome Atlas (TCGA) database. We also showed that abilities regarding migration and invasion were reduced in TMEM211-silenced colon cancer cells (HCT116 and DLD-1). Moreover, TMEM211-silenced colon cancer cells showed decreased levels of Twist1, N-cadherin, Snail and Slug but increased levels of E-cadherin. Levels of phosphorylated ERK, AKT and RelA (NF-κB p65) were also decreased in TMEM211-silenced colon cancer cells. Our findings indicate that TMEM211 regulates epithelial–mesenchymal transition for metastasis through coactivating the ERK, AKT and NF-κB signaling pathways, which might provide a potential prognostic biomarker or therapeutic target for colon cancer patients in the future.
Surface Modification Techniques for Polyetheretherketone as Spinal Interbody Fusion Cage Material to Stimulate Biological Response: A Review
Authors: Liu Shu , Sui Junhao , Chen Kai , Ding Yun , Chang Xinyu , Hou Yijin , Zhang Lin , Meng Xiangyu , Xu Zihao , Miao Licai , Huo Shicheng , Wang Guangchao , Shi Zhicai
Published: May 2023

Currently, spinal interbody cages are crucial for spinal fusion surgeries. Due to the mechanical and imaging characteristics of polyetheretherketone (PEEK), it is a widely used material for cages. However, the bioinert PEEK has poor osseointegration, thereby preventing the ideal fusion of PEEK cages. Therefore, efforts have been made for improving biological activity using surface modification techniques, including physical as well as chemical modifications and surface coating. In this study, we reviewed and analyzed recent studies on PEEK surface modification techniques to enhance our understanding for future studies.
Processing and Weathering of Sol-Gel Clearcoats for Coil-Coated Steel
Authors: Watkins Evan , Griffiths Chris , Batchelor Chris , Barker Peter , Carnie Matt
Published: May 2023

Clearcoats provide long-term aesthetics and protection for underlying coating systems, increasing product lifetimes. However, organic clearcoats are predominantly produced using fossil-fuel feedstocks. In search of a sustainable alternative, an experimental investigation was conducted on the development of glass-like clearcoats produced using the sol-gel process. The processing of sol-gel clearcoats over a pigmented polyurethane coating was studied by modifying the sol-gel solution pH, ageing, curing, precursor chemistry and deposition techniques. Under optimal formulation and processing conditions, defect-free sol-gel clearcoats were produced that have the potential to be scaled up to a coil-coating line using existing technologies. Mechanical testing demonstrated the coatings had excellent adhesion, hardness, and flexibility. Furthermore, accelerated laboratory weathering tests revealed the sol-gel coatings had superior degradation resistance compared to the organic coatings tested, resulting in negligible colour changes and higher gloss retention after 4000 h of exposure. The durability and environmental benefits of sol-gel clearcoats highlight their potential as a replacement for traditional organic clearcoats in a variety of applications.
Diversity and Conservation of Bats in Saudi Arabia
Authors: Al Obaid Ahmed , Shuraim Faisal , Al Boug Ahmad , Al Jbour Sharif , Neyaz Farah , Aloufi Abdul Hadi , Amr Zuhair
Published: May 2023

The bats of Saudi Arabia consist of 30 species and 21 genera within 9 families (Pteropodidae, Rhinopomatidae, Rhinolophidae, Emballonuridae, Nycteridae, Hipposideridae, Miniopteridae, Molossidae, and Vespertilionidae). Some species have been recorded from only one locality: Epomophorus labiatus, Hipposideros megalotis and Asellia patrizii. The taxonomy of some species was updated. Details on the past and present distribution of the bats were included along with available data on their habitat preference and biology. An analysis of the bat fauna of Saudi Arabia revealed that they have six major zoogeographical affinities; Afrotropical (eight species), Saharo-Sindian (three species), Afrotropical-Palaearctic (four species), Palaearctic (four species), oriental (one species), and Afrotropical-oriental (two species). Asellia patrizii stands as an endemic species known only from Eretria, Ethiopia, and Farasan Island in Saudi Arabia, and Rhyneptesicus nasutus is considered as a Middle East endemic species with distribution confined to Iraq, Iran, and Afghanistan, reaching as far as western Arabia. At least six more species are suspected to occur in Saudi Arabia, since they have been reported from neighboring Yemen. The threats to and conservation status of the bats of Saudi Arabia were highlighted.
Feasibility of Optical Genome Mapping in Cytogenetic Diagnostics of Hematological Neoplasms: A New Way to Look at DNA
Authors: Coccaro Nicoletta , Anelli Luisa , Zagaria Antonella , Tarantini Francesco , Cumbo Cosimo , Tota Giuseppina , Minervini Crescenzio Francesco , Minervini Angela , Conserva Maria Rosa , Redavid Immacolata , Parciante Elisa , Macchia Maria Giovanna , Specchia Giorgina , Musto Pellegrino , Albano Francesco
Published: May 2023

Optical genome mapping (OGM) is a new genome-wide technology that can reveal both structural genomic variations (SVs) and copy number variations (CNVs) in a single assay. OGM was initially employed to perform genome assembly and genome research, but it is now more widely used to study chromosome aberrations in genetic disorders and in human cancer. One of the most useful OGM applications is in hematological malignancies, where chromosomal rearrangements are frequent and conventional cytogenetic analysis alone is insufficient, necessitating further confirmation using ancillary techniques such as fluorescence in situ hybridization, chromosomal microarrays, or multiple ligation-dependent probe amplification. The first studies tested OGM efficiency and sensitivity for SV and CNV detection, comparing heterogeneous groups of lymphoid and myeloid hematological sample data with those obtained using standard cytogenetic diagnostic tests. Most of the work based on this innovative technology was focused on myelodysplastic syndromes (MDSs), acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL), whereas little attention was paid to chronic lymphocytic leukemia (CLL) or multiple myeloma (MM), and none was paid to lymphomas. The studies showed that OGM can now be considered as a highly reliable method, concordant with standard cytogenetic techniques but able to detect novel clinically significant SVs, thus allowing better patient classification, prognostic stratification, and therapeutic choices in hematological malignancies.
A Blinded Investigation: Accentuated NK Lymphocyte CD335 (NKp46) Expression Predicts Pregnancy Failures
Authors: Dons’koi Boris V. , Baksheev Serhiy M. , Sudoma Irina O. , Palyha Ihor E. , Khazhylenko Ksenia G. , Zabara Dariia V. , Anoshko Yaroslava I. , Dosenko Viktor E. , Dubrovsky Evgen I.
Published: May 2023

Aim: NKp46 is an NK cell receptor uniquely expressed by NK cells and a small subset of innate lymphoid cells. In our previous studies, we suggested a tight connection between the activity of NK cells and the expression of NKp46 and supported the clinical significance of NKp46 expression in NK cells in women with reproductive failures. In this study, we investigated the expression of NKp46 in NK cells in the peripheral blood of women in early pregnancy and analyzed its association with pregnancy loss. Methods: In a blinded study, we examined blood samples and analyzed the subsequent pregnancy outcomes from 98 early pregnant women (5th–7th week of gestation—w.g.) and 66 women in the 11th–13th week of pregnancy who served as controls. We studied the expression of NKp46 and the levels of anti-cardiolipin antibodies (aCL). The results of aCL were shared with the clinic, while the expression of NKp46 was blinded and not analyzed until the end of the study. Results: A misbalance in the NKp46+NK cells subpopulations was associated with an unfavorable ongoing pregnancy. A decreased level of NKp46high cells (<14%) was strongly associated with miscarriage. A decreased level of the double-bright subpopulation (NKp46hightCD56++) also was a negative prognostic factor for the pregnancy course, but its increased level (>4%) was strongly associated with a successful pregnancy course. Conclusions: Our results showed that accentuated levels of NKp46+NK cells lead to a negative prognosis for early pregnancy courses in women.
Treatments of COVID-19-Associated Taste and Saliva Secretory Disorders
Authors: Tsuchiya Hironori
Published: May 2023

Since the worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, treating taste and saliva secretory disorders associated with coronavirus disease 2019 (COVID-19) has become a critical issue. The aim of the present study was to update information on treatments applicable to such oral symptoms and discuss their pathogenic mechanisms. The literature search indicated that different treatments using tetracycline, corticosteroids, zinc, stellate ganglion block, phytochemical curcumin, traditional herbal medicine, nutraceutical vitamin D, photobiomodulation, antiviral drugs, malic acid sialagogue, chewing gum, acupuncture, and/or moxibustion have potential effects on COVID-19-associated ageusia/dysgeusia/hypogeusia and xerostomia/dry mouth/hyposalivation. These treatments have multiple modes of action on viral cellular entry and replication, cell proliferation and differentiation, immunity, and/or SARS-CoV-2 infection-induced pathological conditions such as inflammation, cytokine storm, pyroptosis, neuropathy, zinc dyshomeostasis, and dysautonomia. An understanding of currently available treatment options is required for dental professionals because they may treat patients who were infected with SARS-CoV-2 or who recovered from COVID-19, and become aware of their abnormal taste and salivary secretion. By doing so, dentists and dental hygienists could play a crucial role in managing COVID-19 oral symptoms and contribute to improving the oral health-related quality of life of the relevant patients.
On the Characteristics of Fatigue Fracture with Rapid Frequency Change
Authors: Amooie Mohammad A. , Lijesh K. P. , Mahmoudi Ali , Azizian-Farsani Elaheh , Khonsari Michael M.
Published: May 2023

The effect of sudden variations in working modes and fatigue behavior of CS 1018 is studied. A general model based on the framework of the fracture fatigue entropy (FFE) concept is developed to capture such changes. Fully reversed bending tests are performed on flat dog bone specimens with a series of variable frequency tests without turning the machine off to simulate fluctuating working conditions. The results are then post-processed and analyzed to assess how fatigue life changes when a component is subjected to sudden changes in multiple frequencies. It is demonstrated that regardless of the frequency changes, FFE remains constant and stays within a narrow band range, similar to that of a constant frequency.
A Systematic Review of Engineering Students in Intercultural Teamwork: Characteristics, Challenges, and Coping Strategies
Authors: Jiang Dan , Dahl Bettina , Du Xiangyun
Published: May 2023

In response to the challenges posed by globalization and internationalization, engineering education programs are increasingly focused on knowledge, technologies, and competence that meet global needs. Against this backdrop, higher engineering students are often encouraged to collaborate in teams with others from diverse, cultural, and disciplinary backgrounds, for the purpose of preparing them to accommodate change and innovation across international working contexts. Within a growing number of intercultural systematic and meta-analysis reviews in engineering education, little attention has been paid to intercultural team characteristics, and even less has been given to the challenges of intercultural teamwork and the relevant coping strategies. Using a systematic approach, this paper reviewed 77 journal articles to identify the intercultural team characteristics of engineering students based on team formats, level of collaboration, learning goals, evaluation methods, and learning gains. Through the process of intercultural collaboration, several challenges and corresponding coping strategies were reported at the individual, relational, and contextual levels. Recommendations for future practice for engineering educators and programs faculties, and future research directions for engineering educational researchers, are proposed in order to support engineering students’ intercultural team learning.