bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting STAT3, FOXO3a, and Pim‐1 kinase by FDA‐approved tyrosine kinase inhibitor–Radotinib: An in silico and in vitro approach
Authors: Manoharan Suryaa , Santhakumar Aksayakeerthana , Perumal Ekambaram
Published: October 2024

Cancer, a multifactorial pathological condition, is primarily caused due to mutations in multiple genes. Hepatocellular carcinoma (HCC) is a form of primary liver cancer that is often diagnosed at the advanced stage. Current treatment strategies for advanced HCC involve systemic therapies which are often hindered due to the emergence of resistance and toxicity. Therefore, a multitarget approach might prove more effective in HCC treatment. The present study focuses on targeting signal transducer and activator of transcription 3 (STAT3), forkhead box class O3a (FOXO3a), and proviral integration site for Moloney murine leukemia virus‐1 (Pim‐1) kinase, using a Food and Drug Administration (FDA)‐approved anticancer drug library. Two compounds, namely, radotinib and capmatinib, were identified as top compounds using molecular docking. Among the two compounds, radotinib exhibited significant binding values towards the targeted proteins and their heterodimers. Furthermore, in vitro experiments involving 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT), live/dead, 4′,6‐diamidino‐2‐phenylindole, and clonogenic assays were performed to evaluate the effect of radotinib in human hepatoblastoma cell line/hepatocellular carcinoma cells. The gene expression data indicated reduced expression of FOXO3a and Pim‐1, but no basal‐level alteration of STAT3. The Western blot analysis assay showed that the phosphorylation level of STAT3 was significantly decreased upon radotinib treatment. Taken together, our findings suggest that radotinib, which is currently used in the treatment of chronic myeloid leukemia (CML), could be considered as a potential candidate for repurposing in the treatment of HCC.
Incidence and Genetic Risk of Juvenile Idiopathic Arthritis in Norway by Latitude
Authors: Hestetun Sigrid V. , Rudsari Hamid K. , Jaholkowski Piotr , Shadrin Alexey , Haftorn Kristine L. , Andersen Svend , Rygg Marite , Nordal Ellen , Frei Oleksandr , Andreassen Ole A. , Selvaag Anne M. , Størdal Ketil , Sanner Helga
Published: October 2024

Objective

We aimed to investigate the incidence of juvenile idiopathic arthritis (JIA) in the three geographic regions of Norway and whether potential regional incidence differences are explained by environmental or genetic factors across regions.

Methods

We conducted a register‐based cohort study including all Norwegian children born from 2004 to 2019, with follow‐up throughout 2020. The JIA diagnosis, defined by at least two International Classification of Diseases, Tenth Revision codes for JIA, was validated against medical records. The incidence rate (IR) and hazard ratio (HR) for JIA were estimated for all Norway and for the North, Mid, and South regions. In a subsample from the Norwegian Mother, Father, and Child Cohort Study (MoBa), the genetic risk for JIA was assessed in the three regions.

Results

After median 9.1 (range 0.3–16.0) years of follow‐up, we identified 1,184 patients with JIA and 910,058 controls. The IR for JIA/100,000 person‐years was 14.4 in all of Norway, 25.9 in the North region, 17.9 in the Mid region, and 12.5 in the South region. The HR (95% confidence interval [CI]) of JIA in the North region was 2.07 (1.77–2.43) and in the Mid region HR 1.43 (95% CI 1.23–1.67) compared with the South region. Adjustments for perinatal factors, socioeconomic status, and early antibiotic exposure did not change our estimates substantially. In MoBa (238 patients with JIA, 57,392 controls), the association between JIA and region of birth was no longer significant when adjusting for genetic factors.

Conclusion

We found a higher incidence of JIA with increasing latitude without evidence for available environmental factors explaining the observed gradient. In contrast, genetic factors modified the association, but further studies are warranted.
The role of online search platforms in scientific diffusion
Authors: Drivas Kyriakos
Published: October 2024

After the launch of Google Scholar older papers experienced an increase in their citations, a finding consistent with a reduction in search costs and introduction of ranking algorithms. I employ this observation to examine how recombination of science takes place in the era of online search platforms. The findings show that as papers become more discoverable, their knowledge is diffused beyond their own broad field. Results are mixed when examining knowledge diffusion within the same field. The results contribute to the ongoing debate of narrowing of science. While there might a general reduction in recombination of knowledge across distant fields over the last decades, online search platforms are not the culprits.
Exosomal miR‐199a‐3p Secreted From Cancer‐Associated Adipocytes Promotes Pancreatic Cancer Progression
Authors: Noda Kazuyoshi , Sato Yasushi , Okada Yasuyuki , Nishida Kensei , Kawano Yutaka , Tanahashi Toshihito , Bando Masahiro , Okamoto Koichi , Takehara Masanori , Sogabe Masahiro , Miyamoto Hiroshi , Daizumoto Kei , Kanayama Hiroomi , Takayama Tetsuji
Published: October 2024

Background

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer. Recent studies indicated that cancer‐associated adipocytes (CAAs) play crucial roles in tumor progression; however, the precise mechanism remains unknown. Here, we analyzed specific exosomal microRNAs (miRNA) signatures derived from pancreatic CAAs to investigate their role in cancer progression.

Methods

CAAs were generated by co‐culturing human adipocytes with human pancreatic cancer cells, and exosomes were isolated from the CAA‐conditioned medium (CAA‐CM). Small RNA‐seq analysis was used to identify differentially expressed miRNAs in these exosomes. The effects of miRNAs on cell proliferation, migration/invasion, and drug sensitivity were examined. Luciferase reporter assays, real‐time polymerase chain reaction, and western blotting were performed to investigate the molecular mechanisms of the miRNAs. The clinical relevance of the miRNAs was investigated using publicly available data and our cohort of patients with PDAC.

Results

miR‐199a‐3p expression was significantly increased in CAA‐CM‐derived exosomes. CAA‐derived exosomes transferred miR‐199a‐3p to pancreatic cancer cells. Transfection with miR‐199a‐3p increased the proliferation, invasion, migration, and drug resistance of pancreatic cancer cells by downregulating SOCS7, increasing STAT3 phosphorylation, and upregulating SAA1 expression. High tissue miR‐199a‐3p expression is correlated with poor prognosis in patients with PDAC. Liquid biopsies revealed that exosomal miR‐199a‐3p could accurately differentiate patients with PDAC from healthy controls. Multivariate survival analysis indicated that miR‐199a is an independent prognostic factor for PDAC.

Conclusion

miR‐199a‐3p in CAA‐derived exosomes contributes to the malignant transformation of pancreatic cancer via the SOCS7/STAT3/SAA1 pathway, suggesting its potential as a biomarker and therapeutic target for PDAC.
Recent Developments and Evolving Therapeutic Strategies in KMT2A‐Rearranged Acute Leukemia
Authors: Yin Lei , Wan Lin , Zhang Youjian , Hua Shenghao , Shao Xuejun
Published: October 2024

Background

Rearrangements of the histone‐lysine‐N‐methyltransferase (KMT2A), previously referred to as mixed‐lineage leukemia (MLL), are among the most common chromosomal abnormalities in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), involving numerous different fusion partners. KMT2A‐rearranged (KMT2A‐r) leukemia is characterized by a rapid onset, aggressive progression, and significantly worse prognosis compared to non‐KMT2A‐r leukemias. Even with contemporary chemotherapeutic treatments and hematopoietic stem cell transplantations (HSCT), patients with KMT2A‐r leukemia typically experience poor outcomes and limited responses to these therapies.

Objectives

This review aims to consolidate recent studies on the general gene characteristics and associated mechanisms of KMT2A‐r acute leukemia, as well as the cytogenetics, immunophenotype, clinical presentation, and risk stratification of both KMT2A‐r‐AML and KMT2A‐r‐ALL. Particularly, the treatment targets in KMT2A‐r acute leukemia are examined.

Methods

A comprehensive review was carried out by systematically synthesizing existing literature on PubMed, using the combination of the keywords ‘KMT2A‐rearranged acute leukemia’, ‘lymphoblastic leukemia’, ‘myeloid leukemia’, and ‘therapy’. The available studies were screened for selection based on quality and relevance.

Conclusions

Studies indicate that KMT2A rearrangements are present in over 70% of infant leukemia cases, approximately 10% of adult AML cases, and numerous instances of secondary acute leukemias, making it a disease of critical concern to clinicians and researchers alike. The future of KMT2A‐r acute leukemia research is characterized by an expanding knowledge of the disease's biology, with an emphasis on personalized therapies, immunotherapies, genomic advancements, and innovative therapeutic combinations. The overarching aim is to enhance patient outcomes, lessen the disease burden, and elevate the quality of life for those affected. Ongoing research and clinical trials in this area continue to offer promising opportunities for refining treatment strategies and improving patient prognosis.
Meta‐Analysis of the Relationship Between Occupational/Environmental Exposure to Wood Dust and Laryngeal Cancer
Authors: Meng E. , Xin Zhou , Jianrui Dou , Jinzhu Yin
Published: October 2024

Objective

Wood dust is a human carcinogen. However, studies examining the relationship between wood dust exposure and laryngeal cancer have yielded inconsistent findings. Therefore, we systematically reviewed relevant studies examining the relationship between wood dust exposure and laryngeal cancer development, followed by a meta‐analysis.

Methods

Publications in the following databases were searched: PubMed, Medline, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI). The Newcastle–Ottawa scale was used to evaluate the study quality. A random‐effects model was used for the meta‐analysis.

Results

Eighteen case–control studies and one cohort study, involving a total of 4426 patients with laryngeal cancer and 319,129 control participants, were identified. The association between occupational/environmental exposure to wood dust and laryngeal cancer, if any, was unclear (adjusted combined OR: 1.11; 95% CI: 0.94–1.31). However, subgroup analyses according to the number of cases, geographic region, publication year, and follow‐up duration revealed correlations between wood dust exposure correlated and laryngeal cancer, as follows: number of cases > 200 (OR: 1.14; 95% CI: 1.01–1.25 [n = 10]); studies conducted in the US (OR: 1.21; 95% CI: 1.07–1.37 [n = 5]); follow‐up time > 5 years (OR: 1.19; 95% CI: 1.07–1.32 [n = 10]); and publication after the year 2000 (OR: 1.15; 95% CI: 1.04–1.28 [n = 8]). A high heterogeneity in the results was observed (I2 = 42.5%, p = 0.024). The results were stable, and no publication bias existed, according to sensitivity analysis.

Conclusions

This meta‐analysis suggests that wood dust exposure is associated with laryngeal cancer. Additional large‐scale studies are warranted to clarify the relationship between wood dust exposure and laryngeal cancer.
Ultrasound Molecular Imaging Enhances High‐Intensity Focused Ultrasound Ablation on Liver Cancer With B7‐H3‐Targeted Microbubbles
Authors: Xiong Xialin , Zhou Hang , Xu Xinzhi , Fu Qihuan , Wan Yujie , Cao Yuting , Tang Rui , Li Fang , Zhang Jun , Li Pan
Published: October 2024

Background

High‐intensity focused ultrasound (HIFU) is a promising minimally invasive treatment for liver cancer; however, its efficacy is often limited by the attenuation of ultrasonic energy. This study investigates the effectiveness of B7‐H3‐targeted microbubbles (T‐MBs) in enhancing HIFU ablation of liver cancer and explores their potential for clinical translation.

Methods

T‐MBs and isotype control microbubbles (I‐MBs) were synthesized through the conjugation of biotinylated anti‐B7‐H3 antibody and isotype control antibody to the microbubble surface, respectively. Contrast‐enhanced ultrasound imaging was performed to compare the accumulation of T‐MBs and I‐MBs in liver cancer at various time points. The efficacy of T‐MBs in enhancing HIFU treatment was evaluated by measuring the immediate tumor ablation rate and long‐term tumor growth suppression. Additionally, the induced antitumor immune response was assessed through cytokine quantification in serum and tumor tissue, along with immunofluorescence staining conducted on days 1, 3, and 7 post‐treatment.

Results

T‐MBs demonstrated superior liver cancer‐specific accumulation, characterized by higher concentrations and prolonged retention compared to I‐MBs. The combination of T‐MBs with HIFU resulted in significantly enhanced tumor ablation rates and superior tumor growth suppression. Post‐treatment analysis revealed a gradual uptick in cytokine levels within the tumor microenvironment, along with progressive infiltration of antitumor immune cells.

Conclusion

T‐MBs effectively enhance the therapeutic efficacy of HIFU for liver cancer treatment while simultaneously promoting an antitumor immune response. These findings provide a strong experimental foundation for the clinical translation of ultrasound molecular imaging combined with HIFU as a novel approach for tumor therapy.
Phytochemical Profiling and Bioactive Potential of Moroccan Pulicaria Mauritanica Essential Oils: In Silico and In Vitro Antibacterial and Antioxidant Assessment
Authors: Sabiri Maryame , Chtibi Houda , Aanouz Ilham , Barbouchi Mohammed , Benali Taoufiq , Alaqarbeh Marwa , Hammani Khalil , Amechrouq Ali , Bouachrine Mohammed
Published: October 2024

A study was conducted to analyze the essential oil of Pulicaria mauritanica (PMEO) and investigate its antibacterial and antioxidant properties using in‐vitro and in‐silico methods. The essential oil was extracted using the hydrodistillation technique, and its chemical composition was identified via GC/MS analysis. The chemical composition of the oil shows that the major components of PMEO are carvotanacetone (67.92 %) followed by 2,5‐dimethoxy‐p‐cymene (3.62 %), eucalyptol (1.76 %) and tetrahydrocarvone (1.32 %). The antibacterial and antioxidant effects against DPPH free radicals and ferric‐reducing power were tested using in‐vitro microdilution method. The antibacterial activity showed a strong sensitivity against Bacillus subtilis and Proteus mirabilis with an inhibition zone of (22.33±1.78 mm and 19.3±0.68 mm, respectively; the lowest MIC and MBC values were (MIC=MBC=1.56 mg/mL). However, computational studies were carried out using molecular docking studies. The analysis of the interaction nature between (PMEO) essential oil and tyrosyl‐tRNA synthetase from Staphylococcus aureus aids in understanding the antibacterial properties of essential oil molecules and their mechanism of action. The in‐silico toxicity and pharmacokinetics results show that 4‐candidate molecules have potential antibacterial properties and suggest that PMEO could be a source of natural antioxidants and antibacterial agents.
Acute disseminated encephalomyelitis (ADEM) in a patient with post streptococcal glomerulonephritis (PSGN): A case report
Authors: Ahmed Aftab , Akbar Anum , Kunwar Digbijay , Mehta Fena
Published: October 2024

Key Clinical Message

Concurrent recurrence of acute disseminated encephalomyelitis (ADEM) and poststreptococcal glomerulonephritis (PSGN) in a thalassemia intermedia patient is rare and underscores the complexity of autoimmune disorders. This case emphasizes the importance of considering ADEM in the differential diagnosis of children presenting with PSGN accompanied by neurological symptoms.

Post‐streptococcal glomerulonephritis (PSGN) is a common group A streptococcal (GAS) infection sequela. The pathophysiology of PSGN involves immune complex deposition, with type 3 hypersensitivity reaction triggered by GAS. Certain neurological conditions may also arise following a GAS infection, possibly due to molecular mimicry in the brain, a pathophysiology similar to rheumatic fever, another common sequel of GAS infection. We present the case of a child with β‐thalassemia intermedia who exhibited the classic triad (edema, hypertension, hematuria) of PSGN along with neurological manifestations, including a low glasgow coma scale (GCS) score and seizures. Magnetic resonance imaging (MRI) of the brain indicated changes consistent with acute disseminated encephalomyelitis (ADEM). Initially treated with methylprednisolone, the patient eventually received intravenous immunoglobulin (IVIG) due to lack of response. The patient had a good outcome, with complete resolution of all symptoms and no residual neurological deficits. This case underscores the importance of considering ADEM in the differential diagnosis for patients presenting with neurological signs and symptoms following a recent throat infection with GAS. Furthermore, given the increased risk of infection in thalassemia, patients with thalassemia who have a throat infection and neurological symptoms should be evaluated for the possible presence of ADEM.
Rapidly worsening lung adenocarcinoma due to diffusely spreading lymphangitic carcinomatosis: A case report
Authors: Tanaka Satoshi , Matsubayashi Ryo , Tamori Shunichi , Saito Katsuhiko , Nomura Satoshi
Published: October 2024

Key Clinical Message

Lymphangitic carcinomatosis is a metastatic disease with a poor prognosis and poorly understood pathophysiology. We present a case of rapidly worsening lung adenocarcinoma with diffusely spreading cancerous lymphangitis in lung, mediastinum, retroperitoneum, and gastrointestinal tract. Our findings suggest cancer dissemination in this patient was predominantly caused by direct lymphatic invasion.
The Role of Spacer Length in Macrocyclization Reactions Under Confinement
Authors: Nandeshwar Muneshwar , Weisser Kilian , Ziegler Felix , Frey Wolfgang , Buchmeiser Michael R.
Published: October 2024

We studied the influence of the distance of olefin metathesis catalysts from the inner surface of a mesoporous support on macrocyclization and Z‐selectivity under confinement. For these purposes, the cationic molybdenum imido alkylidene N‐heterocyclic carbene (NHC) catalysts [Mo(N‐(2‐tBu‐C6H4)(1‐mesityl‐3‐(3‐trimethoxysilylprop‐1‐yl)‐imidazol‐2‐ylidene)(CHCMe2Ph)(MeCN)Br+ B(ArF)4−] Mo2, [Mo(N‐(2‐tBu‐C6H4)(1‐mesityl‐3‐(3‐trimethoxysilylprop‐1‐yl)‐imidazol‐2‐ylidene)(CHCMe2Ph)(MeCN)OTf+ B(ArF)4−] Mo3, [Mo(N‐(2,6‐Me2‐C6H3)(1‐mesityl‐3‐(3‐trimethoxysilylprop‐1‐yl)‐imidazol‐2‐ylidene)(CHCMe2Ph)(MeCN)Br+ B(ArF)4−] Mo5, and [Mo(N‐(2,6‐iPr2‐C6H3)(1‐mesityl‐3‐(3‐trimethoxysilylprop‐1‐yl)‐imidazol‐2‐ylidene)(CHCMe2Ph)(MeCN)+Br B(ArF)4−] Mo7 (B(ArF)4 = tetrakis[3,5‐bis(trifluoromethyl)phenyl]borate), all containing a trimethoxysilylpropyl tether, were selectively immobilized inside the mesopores of SBA‐15. Under confinement, both macro(mono)cyclization (MMC) and Z‐selectivity were higher than in solution but lower than with catalysts directly bound to the surface of the mesoporous supports. These findings are in agreement with existing theoretical models on substrate and product distribution in mesopores, which suggest that the highest substrate concentration is found at the pore wall and that it increases with decreasing pore diameter.
Open‐ESyn: A 3D‐Printed Toolkit for Expanded ElectraSyn Functionality and Reproducibility for Electrosynthesis
Authors: Choi Anthony , Heard David M. , Haydon Calum S. , Lennox Alastair J. J.
Published: October 2024

Electrosynthetic reactions are performed in either custom‐made reactors that are developed and machined in‐house or commercially available systems that offer good reproducibility but come at a high cost. To bridge this divide between customizability and reproducibility, we have developed the Open‐ESyn, which is a suite of 3D‐printed components compatible with the popular ElectraSyn. This collection of parts increases the electrosynthesis that can be performed with the ElectraSyn, expanding, for example, the scale, temperature and the type of electrodes that can be used. The standardized reactor environment can be inexpensively recreated, thereby maintaining the reproducibility of the ElectraSyn ecosystem.
Synthesis of π‐Extended [1.1]Paracyclophanes, [1.1][n]PCP (n=2, 3, and 4), and Their Through‐Space Conjugation
Authors: Kayahara Eiichi , Hirata Saya , Mizuhata Yoshiyuki , Yasuda Yuka , Kusakabe Yu , Kaji Hironori , Yamago Shigeru
Published: October 2024

[1.1][n]Paracyclophanes ([1.1][n]PCPs) (3) with n=2, 3, and 4, which consist of two [n]paraphenylene units connected by methylene bridges, were synthesized using short synthetic pathways with good overall yields. Single‐crystal X‐ray diffraction analyses reveal that the paraphenylene unit in 3 is bent, resulting in an elliptic core structure of 3. The facing bridgehead carbons of the paraphenylene units are separated by a distance much shorter than the sum of the van der Waals radii of sp2‐carbon atoms. UV‐vis absorption spectra, fluorescence spectra, electrochemical measurements, and theoretical calculations were used to demonstrate the presence of through‐space (TS) conjugation in 3. Furthermore, host‐guest complex formation between 3D (n=3) and tetracyanoquinodimethane in the solid state was revealed.
Microstructure Morphology of Chemical and Structural Phase Separation in Thermally Treated KxFe2‐ySe2 Superconductor
Authors: Campi G. , Tomassucci G. , Tanaka M. , Takeya H. , Takano Y. , Mizokawa T. , Saini N. L.
Published: October 2024

The iron‐based KxFe2‐ySe2 superconductor displays chemical, structural and electronic phase separation at nanoscale to microscale, leading to the coexisting metallic phase embedded in an antiferromagnetic host matrix. The metallic character of the system is believed to arise from a percolative granular network affecting its transport in the normal as well as in the superconducting state. This percolative network can be manipulated and controlled through thermal treatments. In this study, we have used scanning X‐ray micro‐fluorescence to visualize morphology of the chemical phase separation coupled to the percolation in KxFe2‐ySe2, manipulated by two distinct thermal treatments, i. e., fast quenching and slow cooling. We find a differing spatial correlation between Fe and K distributions in the two samples, ascribed to a different degree of Fe vacancy ordering. We have also identified an intermediate phase that acts as an interface between the two main phases. The high temperature quenching produces directionally oriented clustered microstructure in which the percolation threshold is lower and hence a more effective transport networks. Instead, the slow cooling results in larger interfaces around the percolation threshold that seems to affect the superconducting properties of the system. The results provide a quantitative characterization of microstructural morphology of differently grown KxFe2‐ySe2 showing potential for the design of electronic devices based on sub‐micron scale chemical phase separation, thus opening avenues for further studies of complex heterogeneous functional structures.
Optimizing Aqueous Zinc‐Sulfur Battery Performance via Regulating Acetonitrile Co‐Solvents and Carbon Nanotube Carriers
Authors: Ge Zhenqiang , Liu Hangning , Wang Shan , Ma Yingjun , Xu Wenhao , Su Linghao , Han Lei , Gong Liangyu , Wang Jie
Published: October 2024

Rechargeable aqueous zinc‐sulfur batteries (AZSBs) are gaining attention due to their high energy density, ultra‐stable discharge platform, and safety. However, poor liquid/solid reaction processes at the anode and cathode reduce reaction kinetics, and the severe dissolution of polysulfides causes shuttle effects during discharge/charge cycles, hindering practical applications. Improving performance requires optimizing both the cathode and electrolyte. Herein, we design an organic‐inorganic hybrid electrolyte (zinc trifluoromethanesulfonate and trace iodine monomer dissolved in an acetonitrile/water co‐solvent (AN‐X)) and a partially exfoliated multi‐walled carbon nanotube (PECNT) hosted sulfur (S@PECNTs) cathode for AZSBs. The sulfur is highly dispersed along the PECNTs with appropriate wettability at the electrode/electrolyte interface using AN‐3 as the electrolyte. Meanwhile, this electrolyte inhibits hydrogen evolution at negative potentials and promotes uniform Zn ion stripping/plating. Expressively, the AN‐3‐based AZSB exhibits a high discharge capacity of 1370 mAh g−1 with excellent Coulombic efficiency (79.9 %), outstanding rate capability, and cycling performance. These improvements are attributed to the synergistic effect between the S@PECNTs and the AN‐3 electrolyte, which reduces Rct to enhance reaction kinetics and blocks the dissolution and shuttle effect of polysulfides, ensuring a reversible reaction between zinc and sulfur.
Influence of WO3 Content in Phosphated Tungsten‐Zirconium Oxide Catalysts on the Catalytic Pathways of Glycerol Transformation
Authors: Vlasenko Nina V. , Kosmambetova Gulnara R. , Senchylo Eugenia V. , Kúš Peter , Veltruská Kateřina , Strizhak Peter E.
Published: October 2024

The catalytic performance of phosphate‐stabilized WOx‐ZrO2 compositions in gas‐phase glycerol dehydration has been investigated. Results show that varying WO3 concentrations direct the process towards either acrolein or allyl alcohol formation. Catalysts with low WOx content exhibit strong Lewis acid sites (Zr4+ and W6+), where these metal ions likely function as redox sites, facilitating glycerol hydrogenolysis to produce allyl alcohol. Higher WOx concentrations (exceeding 20 wt %) lead to the shielding of some W6+ and Zr4+ sites by polytungstate surface complexes, which are strong Brønsted acid sites. This alteration promotes glycerol dehydration through the removal of two water molecules, thereby shifting the selectivity towards acrolein formation.
CircRNome‐wide characterisation reveals the promoting role of circAATF in anti‐PD‐L1 immunotherapy of gallbladder carcinoma
Authors: Wang Yueqi , Li Shengli , Bo Xiaobo , Li Yuan , Wang Changcheng , Nan Lingxi , Zhang Dexiang , Liu Houbao , Zhang Jiwei
Published: October 2024

Circular RNAs (circRNAs) have been shown to play important roles in tumour development and tumour immunology. However, genome‐wide characterisation of circRNAs and their roles in the immunology and immunotherapy of gallbladder carcinoma (GBC) has been lacking. We present a comprehensive characterisation of the circRNA landscape in GBC, revealing GBC‐specific circRNAs. Our analysis found that circRNAs are significantly enriched in cell proliferation and are involved in cancer‐related hallmarks. In particular, circAATF was upregulated in GBC, which was positively correlated with AATF mRNA expression, and promoted GBC cell growth. Through integrating computational and experimental approaches, we revealed that circAATF is positively associated with the CD4+ T cell abundance and PD‐L1 level, and enhances the clinical benefits of anti‐PD‐L1 immunotherapy for GBC. We further demonstrate that circAATF elevates the PD‐L1 level by activating phosphorylated AKT and acting as a sponge for miR‐142‐5p. CircAATF is positively associated with CD4+ T cells and PD‐L1 levels and shows potential to aid anti‐PD‐L1 immunotherapy for GBC. Our study provides insights into roles of circAATF in the tumour development and immunology of GBC and accelerates the development of therapeutic strategies for GBC immunotherapy.

Highlights

We present a comprehensive characterisation of circRNA landscape in gallbladder carcinoma (GBC).

CircAATF is positively associated with CD4+ T cell abundance and PD‐L1 expression and is shown to promote PD‐L1 treatment in mouse model.

CircAATF can elevate PD‐L1 level through phosphorylated AKT and linear AATF, which upregulates PD‐L1 by acting as a sponge of miR‐142‐5p.
Social genomics, cognition, and well‐being during the COVID‐19 pandemic
Authors: Bateman James R. , Krishnamurthy Sudarshan , Quillen Ellen E. , Waugh Christian E. , Kershaw Kiarri N. , Lockhart Samuel N. , Hughes Timothy M. , Seeman Teresa E. , Cole Steve W. , Craft Suzanne
Published: October 2024

INTRODUCTION

Adverse psychosocial exposure is associated with increased pro‐inflammatory gene expression and reduced type‐1 interferon gene expression known as the conserved transcriptional response to adversity (CTRA). CTRA is not well‐studied in cognitive impairment but may contribute to late‐life cognitive decline.

METHODS

We examined perceived stress, loneliness, well‐being, and the impact of coronavirus disease 2019 (COVID‐19) and the relationship to the expression of genes associated with the CTRA. Mixed‐effect linear models were used to quantify associations between psychosocial variables and CTRA gene expression.

RESULTS

Eudaimonic well‐being (EWB) was inversely associated with CTRA gene expression in participants with both normal cognition (NC) and mild cognitive impairment (MCI). Self‐reported coping strategies differed by cognitive status and variably impacted CTRA gene expression.

DISCUSSION

EWB is an important correlate of stress, even in people with MCI. The prodromal cognitive decline appears to moderate the significance of coping strategies as a correlate of CTRA gene expression.

Highlights

Conserved transcriptional response to adversity (CTRA) gene expression is higher with lower eudaimonic well‐being.

Eudaimonic well‐being was important in both participants with normal cognition and those with mild cognitive impairment.

Coping strategies and impact on CTRA gene expression differed by cognitive status.

Loneliness in a population with relatively low loneliness scores did not impact CTRA gene expression.
Gypsum Binder With Increased Water Resistance Derived From Membrane Water Desalination Waste
Authors: Romanovski Valentin , Moskovskikh Dmitry , Tan Hongbin , Kuskov Kirill , Volodko Sergey , Akinwande Abayomi Adewale , Periakaruppan Rajiv , Kong Fanyue , Ma Xiaoling , Yang Feihua , Kamarou Maksim
Published: October 2024

A method has been developed for separating a mixture of calcium, magnesium and sodium sulfates obtained through the interaction of sulfuric acid and waste from the water purification process generated by using membrane filters. The primary goal of this method is to extract gypsum and produce gypsum‐based binders. Patterns were identified regarding how various types, ratio and quantities of additives: blast furnace slag, granite screenings, portland cement, electric steel smelting slag affect the water‐gypsum ratio, strength properties, and water resistance of high‐strength gypsum binders. It was found that adding a single‐component additive specifically to enhance water resistance does not significantly impact these properties. Complex additives have been developed based on Portland cement, granulated blast furnace slag, electric furnace slag, expanded clay dust, and granite screenings of various fractions. These additives are designed to maximize the water resistance of high‐strength gypsum binder based on synthetic calcium sulfate dihydrate. As a result, the water resistance coefficient increased from 0.45 to 0.52. Additionally, a technological block diagram of the process has been proposed.
Synergistic role of prebiotics and probiotics in gut microbiome health: Mechanisms and clinical applications
Authors: Kumari Tapasya , Bag Kshirod Kumar , Das Amit Baran , Deka Sankar Chandra
Published: October 2024

Prebiotic and probiotic usage has exploded, with most formulations promoting gastrointestinal and immunological benefits. Prebiotics modulate the gut microbiota, as a result, short‐chain fatty acids are released into the bloodstream. Prebiotics have immunomodulatory properties that reduce inflammation while enhancing immune responses and boosting gut health. The potential of probiotics has shown steady expansion in the digestive system, metabolic balance, and vaginal health. Probiotics offer therapeutic and preventative strategies for a range of human diseases. The in vitro studies suggested the delivery matrix might influence their effects through physicochemical interactions with molecular and cellular structures as well as modifications in cellular expression. Dietary fibers and polyphenols both contribute significantly to human health protection and can ferment in the gut microbiota to create butyrate. This comprehensive review aims to highlight the probiotics and prebiotics, and provide evidence to support their use in preventive and therapeutic medicine. It is anticipated that it will help the clinical and preclinical research to look into the effects of inclusion and processing on their activity in different food delivery formulations. There are potential opportunities needed to enhance immunological and digestive health by comprehending and using the interaction between the gut microbiota and the immune system in our diet.
Health risk assessment of heavy metals in black tea infusion by Monte Carlo simulation
Authors: Esfarjani Fatemeh , Rouzbahani Mohammad , Behbahan Seyed Ehsan Beladian , Shahbazpour Narges , Moslemi Masoumeh , Abedi Abdol‐Samad
Published: October 2024

Tea leaves and their infusion have been interested in the populations because of their therapeutic and relaxing effects. However, tea plant is prone to heavy metals' bioaccumulation. Regarding the high consumption of tea infusion, concentration of arsenic, cadmium, and lead in black tea infusion was determined by inductively coupled plasma mass spectrometry. Tea infusion was prepared by addition of 45 mL deionized water to 1 g tea leaves followed by heating at 90°C for 10 min. After analysis, carcinogenic and noncarcinogenic risks of heavy metals were investigated by Monte Carlo simulation in two age groups of children and adults younger and older than 15 years old, respectively. According to the results, Hazard Quotient (HQ) of three heavy metals in both children and adults was equal and lower than 0.01. Furthermore, incremental lifetime cancer risk (ILCR) of arsenic in Iranian black tea consumers (<1.5 × 10−6) and lead in all consumers (about 2.55 × 10−7) was within the acceptable range introduced by US EPA (≤10−6). ILCR of arsenic in children and adults consuming foreign tea infusion was within the range of 10−6–10−4. Our further investigation revealed that the highest area (75%–85%) of cumulative frequency distribution for arsenic ILCR in foreign tea consumers was related to ILCR ≤10−5 which is the acceptable range determined by the World Health Organization. Therefore, there was no serious concern about the intake of heavy metals by tea infusion in Iranian children and adults.
Identification of Whey Protein‐Derived Anti‐Obesity Peptides Through 3T3‐L1 Adipocyte Differentiation Assay
Authors: Hirose Yuma , Kurimoto Masaki , Yuda Naoki , Tanaka Miyuki
Published: October 2024

Whey proteins are a rich source of bioactive peptides. Whey protein hydrolysate (WPH) can effectively improve metabolic syndrome and reduce the risk of obesity. Bioactive peptides isolated from various food sources exhibit anti‐obesity effects. However, few reports are available on the identification of anti‐obesity peptides from whey protein. In this study, we aimed to identify anti‐obesity peptides from whey protein. Our findings revealed that WPH suppressed the accumulation of lipid droplets in 3T3‐L1 adipocytes. Anti‐obesity peptides in WPH were identified using amino acid sequencing and LC–MS analysis. Then, the inhibitory effects of the synthetic peptides on adipogenesis were assessed through Oil Red O staining. Two peptides were identified as anti‐adipogenic: LDQW and LKPTPEGDLEIL. Subsequently, real‐time PCR analysis found that several adipogenesis‐related genes, such as peroxisome proliferator‐activated receptor γ, were downregulated in the treatment with these peptides. Furthermore, LDQW and LKPTPEGDLEIL decreased the mRNA expression levels of stearoyl‐coenzyme A desaturase 1 and increased carnitine palmitoyl transferase 1α expression in 3T3‐L1 adipocytes. These findings indicate that LDQW and LKPTPEGDLEIL have anti‐obesity properties and may be beneficial for treating metabolic diseases. This study provides a reference basis for developing new techniques to prevent obesity and related diseases.
A Specific Collagen Hydrolysate Improves Postprandial Glucose Tolerance in Normoglycemic and Prediabetic Mice and in a First Proof of Concept Study in Healthy, Normoglycemic and Prediabetic Humans
Authors: Grasset Estelle , Briand François , Virgilio Nicolina , Schön Christiane , Wilhelm Manfred , Cudennec Benoit , Ravallec Rozenn , Aboubacar Hairati , Vleminckx Sara , Prawitt Janne , Sulpice Thierry , Gevaert Elien
Published: October 2024

In response to nutrients, intestinal L‐ and K‐cells naturally secrete glucagon‐like peptide 1 (GLP‐1). GLP‐1 regulates postprandial blood glucose by increasing insulin secretion, slowing down gastric emptying and inducing satiety. A selection of specifically developed collagen hydrolysates was screened for their ability to enhance natural GLP‐1 production in vitro. The best performing hydrolysate, H80 (Nextida GC), was orally administered at different doses to lean, normoglycemic mice and overweight, prediabetic mice. Lean mice were acutely challenged 45 min before an oral glucose load. While daily supplemented for 6 weeks, prediabetic mice were acutely challenged at day 21 and 34. Oral glucose tolerance, plasma insulin and GLP‐1 levels were assessed, and a gastric emptying assay performed in prediabetic mice. H80 significantly lowered the blood glucose response in lean and prediabetic mice, at a 4 g/kg dose (−25% and −36%, respectively), compared to vehicle. In chronically supplemented, prediabetic mice, acute H80 administration slowed down gastric emptying (−60%) after 21 days and increased plasma insulin (+166%) after 35 days of supplementation. H80 increased plasma active GLP‐1 in lean (+217%) and prediabetic (+860%) mice. Overall, the data indicate that the specific collagen hydrolysate, H80, has significant GLP‐1‐mediated effects on oral glucose tolerance in lean and prediabetic mice. Furthermore, effects on postprandial glucose tolerance were evaluated in a small, human, proof of concept study. H80 reduced the postprandial glucose response at a 5 g dose in healthy, normoglycemic and prediabetic participants. Oral supplementation with H80 might thus be a promising strategy to maintain normal glucose tolerance.
Prevalence of urinary incontinence in postpartum women and physiotherapy interventions applied: An integrative review
Authors: Koomson Gifty , Mgolozeli Siyabulela Eric , Mshunqane Nombeko
Published: October 2024

Objective

This integrative review identified studies that reported the prevalence of physiotherapeutic interventions for urinary incontinence among postpartum women.

Methods

This is an integrative literature review study. We used the integrative literature review framework proposed by Whittemore and Knafl to search for relevant literature.

Search Strategy

The search strategy for electronic databases was developed from the research question and definitions of key concepts, assisted by the librarian. Databases that were searched include Google Scholar, Medline (PubMed), CINAHL, and the Joanna Briggs Institute databases. Both qualitative and quantitative studies that met the inclusion criteria were included. We used the CASP tool to assess the quality of selected papers.

Data Collection and Analysis

The included articles were thematically analyzed. Thirty‐six papers met the inclusion criteria for the review. Six themes emerged from the analysis: prevalence of postpartum UI; risk factors for postpartum UI; antenatal pelvic floor muscle training; conservative treatment and quality of life; experiences of postpartum women with UI; and possible coping strategies adopted by women. Most of the articles were quantitative studies (80.5%); 16.6% were qualitative and 2.7% adopted mixed methods.

Conclusions

Urinary incontinence is common in postpartum women. Antenatal pelvic floor muscle training is protective against postpartum UI and should be the first‐line treatment option.
Does infection with COVID‐2019 during labor increase the risk for obstetric anal sphincter injuries?
Authors: Saban Alla , Leybovitz‐Haleluya Noa , Hershkovitz Reli , Geva Yael , Weintraub Adi Y.
Published: October 2024

Objective

To investigate the association between coronavirus disease 2019 (COVID‐19) infection during the peripartum period and obstetric anal sphincter injuries (OASIS).

Methods

A retrospective cohort study was conducted, including all singleton vaginal deliveries and cesarean deliveries due to failed vacuum extraction, between June 2020 and January 2022 at a large tertiary medical center. OASIS complication during childbirth was compared between women with and without peripartum diagnosis of COVID‐19, defined as a positive polymerase chain reaction test obtained within 1 week before delivery or up to 3 days after delivery. Universal screening for COVID‐19 was implemented. A logistic regression model was used to adjust for confounding variables.

Results

The study included 22 911 women, among whom 468 (2.0%) tested positive for COVID‐19 and 22 443 women had no COVID‐19 diagnosis. After adjusting for confounding variables, peripartum infection with COVID‐19 was found to be independently associated with OASIS (adjusted odds ratio 4.38, 95% confidence interval 2.00–9.61; P < 0.001).

Conclusion

Infection with COVID‐19 during the peripartum period significantly increases the risk for OASIS by more than fourfold. These findings emphasize the importance of understanding the impact of COVID‐19 on birth complications, such as OASIS, to improve public health measures and enhance obstetric outcomes during pandemics.
Cystic Neutrophilic Granulomatous Mastitis Mimicking Breast Cancer: A Case Report
Authors: Shijian Xu , Zhe Hong
Published: October 2024

Cystic neutrophilic granulomatous mastitis (CNGM) is a rare inflammatory breast disease, with a distinct histological pattern characterized. Although it shares clinical and radiological features with other types of granulomatous mastitis, it can sometimes be difficult to distinguish from breast cancer. We report a case of CNGM misdiagnosed as malignant.
The role of radial head morphology in proximal radioulnar joint congruency during forearm rotation
Authors: Zhang Hailong , Yang Guang , Lu Yi
Published: October 2024

Purpose

Congruency of the proximal radioulnar joint (PRUJ) is important in the rotation of the forearm while any compromise would significantly impair the elbow function. The purpose of this study is to determine the morphological features of the radial head and investigate its role in the congruency of the PRUJ during forearm rotation. The hypothesis is that the PRUJ is more congruent in the maximal pronation and supination positions than in the neutral position.

Methods

Thirty sets of computed tomography images of the elbow were acquired, and a three‐dimensional model of the proximal radius and ulna was generated. The radius of curvature of the radial head and the radial head at the maximal pronation, neutral positions and maximal supination were calculated and compared with a one‐way analysis of variance.

Results

The point on the radial head contacting the middle point of radial head at the maximal pronation and supination was located at the ends of the semi‐major axis of the ellipse, while it was located at one end of the semi‐minor axis at neutral position. The radii of curvature of the pronation, neutral and supination points of the radial head were 14.72 ± 1.51, 9.74 ± 1.49 and 14.58 ± 1.70 mm, respectively. The value of the neutral point was significantly smaller than that of the pronation and supination points.

Conclusions

This study quantitatively evaluated the morphology of the radial head and suggested that the best congruency of the PRUJ was achieved at maximal pronation and supination, while the neutral position was associated with the least congruency.

Level of Evidence

Basic Science Study.
Effect of Acetic Acid on Biofilm Formation in Paracidovorax citrulli, Causal Agent of Bacterial Fruit Blotch
Authors: Yang Jincheng , Mao Liang , Gulfam Yousaf , Zeeshan Muhammad , Wang Xiaodong , Fan Ting
Published: October 2024

The unique tissue structure of pathogenic bacteria biofilm plays an important role in its pathogenicity and bactericide resistance. Inhibition or destruction of biofilm formation of pathogenic bacteria is of great significance for the control of plant bacterial diseases. In this study, Paracidovorax citrulli was inoculated into KB medium containing acetic acid, and after shaking at 28°C and 55 r/min for 48 h, it was found that the content of extracellular polysaccharide, extracellular protein and extracellular DNA (eDNA) decreased with the increase of acetic acid concentration, which resulted in the decrease of biofilm formation, it is not even possible to form biofilms on plastic slides. When the final concentration of acetic acid in the culture medium was greater than or equal to 0.5 mg/mL, there was no biofilm on the plastic slides. Therefore, the use of acetic acid as an inhibitor of P. citrulli has a good potential for control of bacterial fruit blotch.
Compound Hot and Dry Events in Argentina and Their Connection to El Niño‐Southern Oscillation
Authors: Lopez‐Ramirez Agustina , Barrucand Mariana , Collazo Soledad
Published: October 2024

This work studies the simultaneous and sequential occurrence of hot and dry months in the summer season in Argentina, north of 40°S, based on three different databases: meteorological stations, a gridded observational dataset and a reanalysis product. The influence of the El Niño‐Southern Oscillation (ENSO) over the occurrence of these compound events is specially analysed using a logistic regression model. Monthly maximum temperature and precipitation data are used for the period 1979–2022 in four sub‐regions of Argentina: Northwestern Argentina (NOA), Northeastern Argentina (NEA), Cuyo (central‐western Argentina) and the Pampas (central‐eastern Argentina). Simultaneous hot and dry months and hot months preceded by dry months are the most frequent compound events. The highest frequencies are found in the centre part of the study region and NEA for simultaneous compound events, and in NOA and the Pampas region for sequential ones. In general terms, all datasets show a good representation of the spatio‐temporal variability of hot and dry months. The insights of the influence of ENSO on compound events revealed that La Niña enhances the occurrences of hot and dry months throughout the study region, with the exception of NOA, where El Niño conditions promote the occurrence of these events. Based on logistic regression models, we successfully quantify the relationship between ENSO and hot and dry months and demonstrate that ENSO plays a significant role as a driver of compound hot and dry events in the central region, Cuyo, NEA and a portion of the Pampas. This research contributes to the understanding of compound events in Argentina and how they are influenced by major drivers of climate variability providing useful information for the development of a predictive system for such events.