bluuebunny/crossref_metadata_2025 huggingface dataset:
GISTs with NTRK Gene Fusions: A Clinicopathological, Immunophenotypic, and Molecular Study
Authors: Cao Zi , Li Jiaxin , Sun Lin , Xu Zanmei , Ke Yan , Shao Bing , Guo Yuhong , Sun Yan
Published: December 2022

The most common mutations in gastrointestinal stromal tumors (GISTs) are KIT or PDGFRA mutations. Recently, neurotrophic tyrosine receptor kinase (NTRK) fusions have been reported in WT GISTs, which increased interest in introducing tropomyosin receptor kinase (TRK) inhibitors as treatments for GISTs with NTRK fusions. Hence, we aimed to screen NTRK fusions in WT GISTs; we used fluorescence in situ hybridization (FISH), next-generation sequencing (NGS), and immunohistochemistry (IHC) to screen NTRK fusions in 46 WT GISTs and evaluate each method. We further reviewed NTRK fusion-positive GISTs from the literature and performed clinical and pathological analyses; two GISTs with an ETV6-NTRK3 fusion (5%) were identified, while only one (50%) was positive for Pan-TRK expression. On the other hand, among the six GISTs with Pan-TRK-positive expression, only one (17%) harbored NTRK fusion. The literature review revealed the strong consistency between FISH and NGS and the limited value of Pan-TRK IHC in screening NTRK fusions in GISTs. In addition, the clinical and pathological analysis showed that GISTs with NTRK rearrangement occurred less frequently in the stomach, were more frequently larger in size, and the epithelioid type presented with a higher risk of recurrence. The NTRK3 fusion has been more common than the NTRK1 fusion in GISTs to date; our study identified two ETV6-NTRK3 fusions in 46 WT GISTs. Compared with FISH and IHC, NGS is preferred for screening WT GISTs, including NTRK rearrangements. However, since GISTs with NTRK fusions are rare, further studies including more samples and mechanistic investigations should be conducted in the future.
Cancer Cells Upregulate Tau to Gain Resistance to DNA Damaging Agents
Authors: Rico Thomas , Denechaud Marine , Caillierez Raphaelle , Comptdaer Thomas , Adriaenssens Eric , Buée Luc , Lefebvre Bruno
Published: December 2022

Recent reports suggested a role for microtubules in double-strand-DNA break repair. We herein investigated the role of the microtubule-associated protein Tau in radio- and chemotherapy. Noticeably, a lowered expression of Tau in breast cancer cell lines resulted in a significant decrease in mouse-xenograft breast tumor volume after doxorubicin or X-ray treatments. Furthermore, the knockdown of Tau impaired the classical nonhomologous end-joining pathway and led to an improved cellular response to both bleomycin and X-rays. Investigating the mechanism of Tau’s protective effect, we found that one of the main mediators of response to double-stranded breaks in DNA, the tumor suppressor p53-binding protein 1 (53BP1), is sequestered in the cytoplasm as a consequence of Tau downregulation. We demonstrated that Tau allows 53BP1 to translocate to the nucleus in response to DNA damage by chaperoning microtubule protein trafficking. Moreover, Tau knockdown chemo-sensitized cancer cells to drugs forming DNA adducts, such as cisplatin and oxaliplatin, and further suggested a general role of Tau in regulating the nuclear trafficking of DNA repair proteins. Altogether, these results suggest that Tau expression in cancer cells may be of interest as a molecular marker for response to DNA-damaging anti-cancer agents. Clinically targeting Tau could sensitize tumors to DNA-damaging treatments.
5-Azacytidine-Mediated Modulation of the Immune Microenvironment in Murine Acute Myeloid Leukemia
Authors: Ebelt Nancy D. , Manuel Edwin R.
Published: December 2022

Cancer cells accumulate epigenetic modifications that allow escape from intrinsic and extrinsic surveillance mechanisms. In the case of acute myeloid leukemias (AML) and myelodysplastic syndromes, agents that disrupt chromatin structure, namely hypomethylating agents (HMAs), have shown tremendous promise as an alternate, milder treatment option for older, clinically non-fit patients. HMAs reprogram the epigenetic landscape in tumor cells through the reversal of DNA hypermethylation. Therapeutic effects resulting from these epigenetic changes are incredibly effective, sometimes resulting in complete remissions, but are frequently lost due to primary or acquired resistance. In this study, we describe syngeneic murine leukemias that are responsive to the HMA 5-azacytidine (5-Aza), as determined by augmented expression of a transduced luciferase reporter. We also found that 5-Aza treatment re-established immune-related transcript expression, suppressed leukemic burden and extended survival in leukemia-challenged mice. The effects of 5-Aza treatment were short-lived, and analysis of the immune microenvironment reveals possible mechanisms of resistance, such as simultaneous increase in immune checkpoint protein expression. This represents a model system that is highly responsive to HMAs and recapitulates major therapeutic outcomes observed in human leukemia (relapse) and may serve as a pre-clinical tool for studying acquired resistance and novel treatment combinations.
Predictive Factors for Local Recurrence after Intraoperative Microwave Ablation for Colorectal Liver Metastases
Authors: Wada Yoshiyuki , Takami Yuko , Ryu Tomoki , Uchino Yoshihiro , Kugiyama Tota , Nomura Yoriko , Saitsu Hideki
Published: December 2022

This study aimed to clarify local recurrence (LR) predictive factors following intraoperative microwave ablation (MWA) for colorectal liver metastases. The data from 195 patients with 1392 CRLM lesions, who were preoperatively diagnosed by gadolinium-enhanced MRI with diffusion-weighted imaging and dynamic CT and treated with intraoperative MWA (2450 MHz) with or without hepatectomy, from January 2005 to December 2019, were retrospectively reviewed and analyzed using logistic regression. In addition, the margins were measured on contrast-enhanced CT 6 weeks post-ablation. Overall, 1066 lesions were ablated. The LRs occurred in 44 lesions (4.1%) among 39 patients (20.0%). The multivariate analysis per patient showed that tumor size > 20 mm and ablation margin < 5 mm were significant predictors for LR. Furthermore, multivariate analysis per lesion revealed that segments 1, 7, and 8 and tumor size > 15 mm, ablation margin < 5 mm, tumor size > 20 mm, and proximity to the Glisson were significant LR predictors. Finally, the outcome of this study may help determine indications for MWA.
The Current and Future Promises of Combination Radiation and Immunotherapy for Genitourinary Cancers
Authors: Saidian Ava , Dolendo Isabella , Sharabi Andrew , Stewart Tyler F. , Rose Brent , McKay Rana R. , Bagrodia Aditya , Salmasi Amirali
Published: December 2022

As the indications for the use of immunotherapy in genitourinary malignancies expand, its role in combination with standard or conventional therapies has become the subject of contemporary studies. Radiotherapy has multiple immunomodulating effects on anti-tumor immune response, which highlights potential synergistic role with immunotherapy agents. We sought to review the body of published data studying the combination of immunotherapy and radiotherapy as well as the rationale for combination therapy. Trial information and primary articles were obtained using the following terms “immunotherapy”, “radiotherapy”, “prostate cancer”, and “bladder cancer.” All articles and trials were screened to ensure they included combination radiotherapy and immunotherapy. The effects of radiation on the immune system, including both immunogenic and immunosuppressive effects, have been reported. There is a potential for combinatorial or synergistic effects between radiation therapy and immunotherapy in treating bladder and prostate cancers. However, results from ongoing and future clinical trials are needed to best integrate immunotherapy into current standard of care treatments for GU cancers.
The FDA-Approved Drug Pyrvinium Selectively Targets ER+ Breast Cancer Cells with High INPP4B Expression
Authors: Rodgers Samuel J. , Ooms Lisa M. , Mitchell Christina A.
Published: December 2022

The majority of breast cancers are estrogen receptor-positive (ER+), and endocrine therapies that suppress ER signaling are the standard-of-care treatment for this subset. However, up to half of all ER+ cancers eventually relapse, highlighting a need for improved clinical therapies. The phosphoinositide phosphatase, INPP4B, is overexpressed in almost half of all ER+ breast cancers, and promotes Wnt/β-catenin signaling, cell proliferation and tumor growth. Here, using cell viability assays, we report that INPP4B overexpression does not affect the sensitivity of ER+ breast cancer cells to standard-of-care treatments including the anti-estrogen 4-hydroxytamoxifen (4-OHT) or the PI3Kα inhibitor alpelisib. Examination of four small molecule Wnt inhibitors revealed that ER+ breast cancer cells with INPP4B overexpression were more sensitive to the FDA-approved drug pyrvinium and a 4-OHT-pyrvinium combination treatment. Using 3D culture models, we demonstrated that pyrvinium selectively reduced the size of INPP4B-overexpressing ER+ breast cancer spheroids in the presence and absence of 4-OHT. These findings suggest that repurposing pyrvinium as a Wnt inhibitor may be an effective therapeutic strategy for human ER+ breast cancers with high INPP4B levels.
Time for Dynamic Assessment of Fitness in Acute Myeloid Leukemia
Authors: Palmieri Raffaele , Maurillo Luca , Del Principe Maria Ilaria , Paterno Giovangiacinto , Walter Roland Bruno , Venditti Adriano , Buccisano Francesco
Published: December 2022

Informed treatment decision-making in acute myeloid leukemia (AML) requires a comprehensive evaluation of all clinical and biological features that may affect the outcome with any given type or intensity of therapy [...]
Recent Advances in Minimally Invasive Liver Resection for Colorectal Cancer Liver Metastases—A Review
Authors: Lo Winifred M. , Tohme Samer T. , Geller David A.
Published: December 2022

Minimally invasive surgical (MIS) approaches to liver resection have been increasingly adopted into use for surgery on colorectal cancer liver metastases. The purpose of this review is to evaluate the outcomes when comparing laparoscopic liver resection (LLR), robotic liver resection (RLR), and open liver resection (OLR) for colorectal cancer liver metastases (CRLM) in 39 studies (2009–2022) that include a case-matched series, propensity score analyses, and three randomized clinical trials. LLR is associated with less intraoperative blood loss and shorter hospital stay compared with OLR. LLR can be performed with comparable operative time. LLR has similar rates of perioperative complications and mortality as OLR. There were no significant differences in 5-year overall or disease-free survival between approaches. Robotic liver resection (RLR) has comparable perioperative safety to LLR and may improve rates of R0 resection in certain patients. Finally, MIS approaches to the hepatic resection of CRLM reduce the time from liver resection to initiation of adjuvant chemotherapy. Thus, MIS liver surgery should be considered in the array of options for patients with CRLM, though thoughtful patient selection and surgeon experience should be part of that decision.
Controversies and Opportunities in the Clinical Daily Use of the 21-Gene Assay for Prognostication and Prediction of Chemotherapy Benefit in HR+/HER2- Early Breast Cancer
Authors: Jacobs Flavia , Gaudio Mariangela , Benvenuti Chiara , De Sanctis Rita , Santoro Armando , Zambelli Alberto
Published: December 2022

Several multigene assays have been developed to help clinicians in defining adjuvant treatment for patients with hormone-receptor-positive (HR+), human epidermal growth factor receptor-2 (HER2)–negative early breast cancer. Despite the 21-gene assay having been available for decades, it has only recently been included in the healthcare systems of several countries. Clinical optimisation of the test remains of critical interest to achieve a greater impact of genomic information in HR+/HER2- early breast cancer. Although current guidelines recommend the use of the 21-gene assay in early breast cancer at intermediate risk of relapse, the implication of the Recurrence Score (RS) in some grey areas still remains uncertain. Our aim is to critically discuss the role of RS in peculiar circumstances. In particular, we focus on the complex integration of genomic data with clinicopathological factors; the potential clinical impact of RS in node-positive premenopausal women and in the neoadjuvant setting; the significance of RS in special histologies and in male patients; and the management and time-optimisation of test ordering. In the absence of robust evidence in these areas, we provide perspectives for improving the use of the 21-gene assay in the decision-making process and guide adjuvant treatment decisions even in challenging cases.
Regulation of Kinase Signaling Pathways by α6β4-Integrins and Plectin in Prostate Cancer
Authors: Koivusalo Saara , Schmidt Anette , Manninen Aki , Wenta Tomasz
Published: December 2022

Hemidesmosomes (HDs) are adhesive structures that ensure stable anchorage of cells to the basement membrane. They are formed by α6β4-integrin heterodimers and linked to intermediate filaments via plectin. It has been reported that one of the most common events during the pathogenesis of prostate cancer (PCa) is the loss of HD organization. While the expression levels of β4-integrins are strongly reduced, the expression levels of α6-integrins and plectin are maintained or even elevated, and seem to promote tumorigenic properties of PCa cells, such as proliferation, invasion, metastasis, apoptosis- and drug-resistance. In this review, we discuss the potential mechanisms of how HD components might contribute to various cellular signaling pathways to promote prostate carcinogenesis. Moreover, we summarize the current knowledge on the involvement of α6β4-integrins and plectin in PCa initiation and progression.
An Ecologic Study of the Association between 1,3-Dichloropropene and Pancreatic Cancer
Authors: McGwin Gerald , Griffin Russell L
Published: December 2022

Background: 1,3-Dichloropropene (1,3-D) is a soil fumigant that is used to protect fruit, vegetable, field, tree, and vine crops from nematode infestation and soil borne diseases. It is a commonly use pesticide, is applied by either direct injection into the soil or drip irrigation and is highlight volatile. Though currently classified as “Suggestive Evidence of Carcinogenic Potential”, the literature in animal-based studies has inconsistent results and there is limited research among a human population with one study only among the California population. The purpose of the current analysis is to conduct a state-level analysis of the association between 1,3-D and pancreatic cancer mortality. Methods: Data for this ecological study were derived from death certificate data (for pancreatic mortality) from 1999 to 2020 and United States Geologic Survey National Water-Quality Assessment project for years 1992–2016 (1,3-D use). A negative binomial regression adjusted for selected lifestyle risk factors of pancreatic cancer (i.e., obesity, alcohol use, and smoking prevalence) estimated rate ratios (RRs) and associated 95% confidence intervals (CIs)for the association between 1,3-D quartiles and pancreatic cancer mortality rate. Models lagged in five-year increments to account for the induction period of pancreatic cancer. Results: Overall, there was no association between 1,3-D quartile and pancreatic cancer mortality rate; however, limiting the analyses to states reporting 1,3-D use for at least 20 years, the highest quartile of 1,3-D use was associated with an 11% increase in the pancreatic cancer mortality rate in the five-year lagged model (RR 1.11, 95% CI 1.06–1.16). This association was consistent across the other lag periods. Conclusions: Accounting for lifestyle factors associated with pancreatic cancer risk, there is a significantly increase rate of pancreatic cancer mortality among states that have the highest quartile of 1,3-D use and have been using 1,3-D for a long-term period.
Effect of Zinc on the Structure and Activity of the Cobalt Oxide Catalysts for NO Decomposition
Authors: Karásková Kateřina , Pacultová Kateřina , Bílková Tereza , Fridrichová Dagmar , Koštejn Martin , Peikertová Pavlína , Stelmachowski Paweł , Kukula Pavel , Obalová Lucie
Published: December 2022

Co4−iZniMnAlOx mixed oxides (i = 0, 0.5 and 1) were prepared by coprecipitation, subsequently modified with potassium (2 or 4 wt.% K), and investigated for direct catalytic NO decomposition, one of the most attractive and challenging NOx abatement processes. The catalysts were characterised by atomic absorption spectroscopy, powder X-ray diffraction, Raman and infrared spectroscopy, temperature-programmed reduction by hydrogen, the temperature-programmed desorption of CO2 and NO, X-ray photoelectron spectroscopy, scanning electron microscopy, the work function, and N2 physisorption. The partial substitution of cobalt increased the specific surface area, decreased the pore sizes, influenced the surface composition, and obtained acid-base properties as a result of the higher availability of medium and strong basic sites. No visible changes in the morphology, crystallite size, and work function were observed upon the cobalt substitution. The conversion of NO increased after the Co substitution, however, the increase in the amount of zinc did not affect the catalytic activity, whereas a higher amount of potassium caused a decrease in the NO conversion. The results obtained, which were predominantly the acid-base characteristics of the catalyst, are in direct correlation with the proposed NO decomposition reaction mechanisms with NOx− as the main reaction intermediates.
Kinetic Modeling of Glycerol Hydrogenolysis: A Short Review
Authors: Liu Yangzi , Liu Jiayu , Xing Zhihao , Zhang Xueqian , Luo Chen , Yan Wenjuan , Jin Xin
Published: December 2022

Glycerol hydrogenolysis represents one of the most promising technologies for future bio-refineries. In this context, kinetic modeling provides key quantitative assessment of the significance of various reactions for process development. However, as of present, there are only limited studies on detailed kinetic modeling of glycerol conversion to 1,2-propanediol, ethylene glycol and other alcoholic products. In this work, a comprehensive summary on kinetic modeling of glycerol hydrogenolysis has been conducted to reveal the possible mechanism involved in the activation of the C-H and C-O bond in glycerol molecules. In particular, power law and Langmuir–Hinshelwood model types have been critically discussed with mechanistic insights. The outcome of this review article will offer alternative views on the scale-up design of glycerol hydrogenolysis to glycols, as well as hydrogenolysis of various other bio-derived compounds to value-added chemicals.
Samarium-Mediated Asymmetric Synthesis
Authors: Majee Suman , Ray Devalina , Banik Bimal Krishna
Published: December 2022

Samarium is an efficient reducing agent, a radical generator in cyclization and a cascade addition reaction. Interestingly, samarium metal has crucial impact on numerous C-C and C-X (X = hetero atom) bond forming transformations. It has been established as an exceptional chemo-selective and stereoselective reagent. The reactivity of the samarium catalyst/reagent is remarkably enhanced in the presence of various additives, ligands and solvents through effective coordination and an increase in reduction potential. It has inherent character to act as electron donor for a wide range of transformations including the asymmetric version of various reactions. This review accentuates the developments in samarium-mediated/catalyzed asymmetric organic synthesis over the past 12 years, where the chirality has been induced from ligand, a nearby asymmetric center within the substrate or through coordination directed stereospecific reactions.
UV and Zero-Valent Iron (ZVI) Activated Continuous Flow Persulfate Oxidation of Municipal Wastewater
Authors: Kanafin Yerkanat N. , Abdirova Perizat , Kanafina Dinara , Arkhangelsky Elizabeth , Kyzas George Z. , Poulopoulos Stavros G.
Published: December 2022

Currently, sulfate-radical-based advanced oxidation processes are promising candidates to become viable post-treatment processes for wastewater purification. In this work, a continuous flow UV light/persulfate (PS)/zero-valent iron (ZVI) system has been applied for wastewater treatment for the first time. The influence of certain photo-Fenton-like process parameters, such as space time, PS concentration, and PS to ZVI molar ratio, on the removal of total organic carbon (TOC), was examined using the Box–Behnken design. First, synthetic municipal wastewater was used for the experiments, and the polynomial regression model was constructed utilizing the real data by using the response surface methodology (RSM). The adequacy of the RSM model was assessed by analysis of variance, which showed that the model was reliable and could be applied to improve the process parameters for TOC removal. Moreover, both synthetic and real municipal wastewater were spiked with carbamazepine (CBZ), which is commonly prescribed as an antiepileptic drug, to investigate its fate in the UV/PS/ZVI system. With a space time of 60 min, PS concentration of 60 mM, and PS to ZVI molar ratio of 15, it was possible to remove 71% of TOC and completely remove CBZ from the synthetic municipal wastewater, whereas a 60% TOC removal and complete removal of CBZ were achieved at a space time of 50 min, PS concentration of 50 mM, and PS/ZVI molar ratio of 15 for the real municipal wastewater. This difference in TOC removal could possibly be linked to the complex matrix of the real wastewater and the presence of radical scavenging agents.
Kinetic, Thermodynamic, and Mechanistic Studies on the Effect of the Preparation Method on the Catalytic Activity of Synthetic Zeolite-A during the Transesterification of Waste Cooking Oil
Authors: Sayed Mohamed Adel , Ahmed Sayed A. , Othman Sarah I. , Allam Ahmed A. , Al Zoubi Wail , Ajarem Jamaan S. , Abukhadra Mostafa R. , Bellucci Stefano
Published: December 2022

Egyptian kaolinite was applied in the synthesis of zeolite-A by conventional hydrothermal and alkali fusion methods, resulting in two forms of zeolite-A: the hydrated phase (H.ZA) and the dehydrated phase (DH.ZA). The DH.ZA phase exhibits an enhanced surface area (488 m2/g), total basicity (7.73 mmol OH/g), high sodium content (20.2%), and a narrow particle size distribution (5 to 25 µm) as compared to the H.ZA phase (423 m2/g surface area, 5.88 mmol OH/g total basicity, 13.3% sodium content, and 10 to 45 µm particle size distribution). DH.ZA exhibits enhanced catalytic activity, achieving a biodiesel yield of 96.8% after 60 min at 60 °C, while the application of H.ZA resulted in a 95.8% yield after 120 min at 80 °C. The controlled transesterification mechanism in the presence of H.ZA and DH.ZA involved robust base-catalyzed reactions. The reactions follow the pseudo-first-order kinetics, and the rate constants (Kc) were determined at three different temperature values (40, 50 and 60 °C). The activation energies using H.ZA (35.9 kJ·mol−1) and DH.ZA (32.714 kJ·mol−1) demonstrates their efficiencies in mild conditions. The thermodynamic parameters of enthalpy (33.23 kJ·mol−1 (H.ZA) and 30.03 kJ·mol−1 (DH.ZA)), Gibb’s free energy (65.164 kJ·mol−1 (H.ZA) and 65.268 kJ·mol−1 (DH.ZA)), and entropy (−195.59 J·K−1·mol−1 (H.ZA) and −195.91 J·K−1·mol−1 (DH.ZA)) demonstrate the spontaneous and endothermic behaviours of these reactions. The obtained biodiesel matches the physical properties of the international standards, and the recyclability properties of the two zeolite phases demonstrate their suitability for commercial-scale applications.
Application of Endoxylanases of Bacillus halodurans for Producing Xylooligosaccharides from Empty Fruit Bunch
Authors: Thirametoakkhara Chanakan , Hong Yi-Cheng , Lerkkasemsan Nuttapol , Shih Jian-Mao , Chen Chien-Yen , Lee Wen-Chien
Published: December 2022

Endo-1,4-β-xylanase catalyzes the random hydrolysis of β-1,4-D-xylosidic bonds in xylan, resulting in the formation of oligomers of xylose. This study aims to demonstrate the promise of endoxylanases from alkaliphilic Bacillus halodurans for the production of xylooligosaccharides (XOS) from oil palm empty fruit bunch (EFB) at high pH. Two enzyme preparations were employed: recombinant endoxylanase Xyn45 (GH10 xylanase) and nonrecombinant endoxylanases, a mixture of two extracellular endo-1,4-β-xylanases Xyn45 and Xyn23 (GH11 xylanase) produced by B. halodurans. EFB was first treated with an alkaline solution. Then, the dissolved xylan-containing fraction was retained, and a prepared enzyme was added to react at pH 8 to convert xylan into XOS. Compared with the use of only Xyn45, the combined use of Xyn45 and Xyn23 resulted in a higher yield of XOS, suggesting the synergistic effect of the two endoxylanases. The yield of XOS obtained from EFB was as high as 46.77% ± 1.64% (w/w), with the xylobiose-to-xylotriose ratio being 6:5. However, when the enzyme activity dose was low, the product contained more xylotriose than xylobiose. Four probiotic lactobacilli and bifidobacteria grew well on a medium containing XOS from EFB. The presence of XOS increased cell mass and reduced pH, suggesting that XOS promoted the growth of probiotics.
Photocatalytic Degradation and Mineralization of Estriol (E3) Hormone Using Boron-Doped TiO2 Catalyst
Authors: Ramírez-Quintanilla Laura Yanneth , Pino-Sandoval Diego , Murillo-Sierra Juan Camilo , Guzmán-Mar Jorge Luis , Ruiz-Ruiz Edgar J. , Hernández-Ramírez Aracely
Published: December 2022

In this research work, boron-doped titanium oxide (B-TiO2) was prepared by the sol-gel method to investigate its behavior in the degradation of the recalcitrant hormone estriol (E3). The doped photocatalyst was synthesized at different boron/titania ratios of 2, 3, and 5 wt.% of boron with respect to the TiO2 content. The obtained materials were characterized by UV-Vis diffuse reflectance spectroscopy (DRS), X-ray diffraction (XRD), Raman spectroscopy, Scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS). The textural properties, specific surface area, and porosity were obtained from N2 adsorption–desorption isotherms by BET and BJH methods, respectively. The photocatalytic performance of each synthesized catalyst was evaluated on the degradation of an aqueous solution (10 mg/L) of estriol (E3) under simulated solar radiation. The variation in the hormone concentration was determined by the HPLC technique, and the mineralization was evaluated by the quantification of total organic carbon (TOC). The obtained results indicated that the catalyst with 3 wt.% of boron incorporation exhibited the best performance on the degradation and mineralization of estriol, achieving its complete degradation at 300 kJ/m2 of accumulated energy and 71% of mineralization at 400 kJ/m2 (2 h) obtaining a non-toxic effluent.
Mixed Oxides Derived from Hydrotalcites Mg/Al Active in the Catalytic Transfer Hydrogenation of Furfural to Furfuryl Alcohol
Authors: López-Asensio Raquel , Cecilia-Buenestado Juan Antonio , Herrera-Delgado Concepción , Larrubia-Vargas María Ángeles , García-Sancho Cristina , Maireles-Torres Pedro Jesús , Moreno-Tost Ramón
Published: December 2022

Herein, a family of Mg/Al hydrotalcites was synthesized as catalytic precursors of MgAlOx mixed oxides. Both hydrotalcites and mixed oxides were characterized and the mixed oxides were tested in the reduction of furfural to yield furfuryl alcohol by MPV reaction using isopropanol as hydrogen donor. Different catalytic parameters were tested, such as the type of alcohol, calcination temperature of the hydrotalcite, and reaction temperature. Furfural and isopropanol were adsorbed on the MgAl-3 catalyst to follow the species adsorbed on the catalyst by FTIR analysis. The results showed that the isopropanol was activated as isopropoxide and furfural changed the adsorption site with increasing temperature but maintaining the h1-conformation. The catalytic performances were associated with the basicity of the catalysts and the deactivation processes have been attributed to the existence of adsorbed species on the surface, mainly due to furfural-derived compounds. The catalysts were reused in three consecutive cycles showing a sharp drop of catalytic activity. To recover the activity, the catalysts were calcined at 500 °C but the activity was only partially recovered. The XPS analysis after reactivation showed that the catalyst surface was modified due to the segregation of hydroxides of Mg and Al.
Solvothermal Synthesis of g-C3N4/TiO2 Hybrid Photocatalyst with a Broaden Activation Spectrum
Authors: Imbar Amit , Vadivel Vinod Kumar , Mamane Hadas
Published: December 2022

A solvothermal self-made composite of graphitic carbon nitride (g-C3N4) and commercially available titanium dioxide (TiO2) demonstrated the removal of commercial acid green-25 (AG-25) textile dye in a saline water matrix when activated by ultraviolet (UV) and visible light. The g-C3N4-TiO2 composite was characterized by X-ray diffraction (XRD), Nitrogen sorption–desorption recording and modeling by the Brunauer–Emmett–Teller (BET) theory, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), diffuse reflectance spectroscopy (DRS), X-ray photoelectron spectroscopy (XPS), photoluminescence (PL), and electron spin resonance (ESR). The solvothermal process did not modify the crystalline structure of the g-C3N4 and TiO2 but enhanced the surface area by interlayer delamination of g-C3N4. Under a simulated solar spectrum (including UVA/B and vis wavelengths), the degradation rate of AG-25 by the composite was two and four times higher than that of TiO2 and pure g-C3N4, respectively (0.04, 0.02, and 0.01 min−1). Unlike TiO2, the g-C3N4-TiO2 composite was activated with visible light (the UV portion of the solar spectrum was filtered out). This work provides insight into the contribution of various reactive oxidative species (ROS) to the degradation of AG-25 by the composite.
Revisiting the Semi-Hydrogenation of Phenylacetylene to Styrene over Palladium-Lead Alloyed Catalysts on Precipitated Calcium Carbonate Supports
Authors: Zheng Yifan , Gu Lin , Li Yining , Ftouni Jamal , Dutta Chowdhury Abhishek
Published: December 2022

The quest for improved heterogeneous catalysts often leads to sophisticated solutions, which are expensive and tricky to scale up industrially. Herein, the effort to upgrade the existing inorganic nonmetallic materials has seldom been prioritized by the catalysis community, which could deliver cost-effective solutions to upgrade the industrial catalysts catalog. With this philosophy in mind, we demonstrate in this work that alloyed palladium-lead (Pd-Pb) deposited on novel precipitated calcium carbonate (PCC) supports could be considered an upgraded version of the industrial Lindlar catalyst for the semi-hydrogenation of phenylacetylene to styrene. By utilizing PCC supports of variable surface areas (up to 60 m2/g) and alloyed Pd-Pb loading, supported by material characterization tools, we showcase that achieving the “active-site isolation” feature could be the most pivotal criterion to maximize semi-hydrogenated alkenes selectivity at the expense of prohibiting the complete hydrogenation to alkanes. The calcite phase of our PCC supports governs the ultimate catalysis, via complexation with uniformly distributed alloyed Pb, which may facilitate the desired “active-site isolation” feature to boost the selectivity to the preferential product. Through this work, we also advocate increasing research efforts on mineral-based inorganic nonmetallic materials to deliver novel and improved cost-effective catalytic systems.
UV-Visible-Near-Infrared-Driven Photoelectrocatalytic Urea Oxidation and Photocatalytic Urea Fuel Cells Based on Ruddlensden–Popper-Type Perovskite Oxide La2NiO4
Authors: Xiong Mingwen , Tao Ying , Fu Lanlan , Pan Donglai , Shi Yuxin , Hu Tong , Ma Jiayu , Chen Xiaofeng , Li Guisheng
Published: December 2022

Photocatalysis and photoelectrocatalysis, as green and low-cost pollutant treatment technologies, have been widely used to simultaneously degrade pollutants and produce clean energy to solve the problems of environmental pollution and energy crisis. However, the disadvantages of photocatalysts in a narrow absorption range and low utilization rate of solar energy still hinder the practical application. Here we fabricate two-dimensional porous Ruddlensden–Popper type nickel-based perovskite oxide La2NiO4 as a noble metal-free photoanode for photoelectrocatalytic urea oxidation under full spectrum sunlight irradiation. The transient photocurrent density under near infrared (NIR) light (λ > 800 nm) can reach 50 μA cm−2. Urea wastewater was used as the fuel to obtain low-energy hydrogen production, and round-the-clock hydrogen production was achieved with the optimal yield of 22.76 μmol cm−2 h−1. Moreover, a photocatalytic urea fuel cell (PUFC) was constructed with La2NiO4 as the photoanode. The power density under UV-vis-NIR was 0.575 μW cm−2. Surprisingly, the filling factor (FF) under NIR light was 0.477, which was much higher than those under UV-vis-NIR and visible light. The results demonstrated that PUFCs constructed from low-cost nickel-based perovskite oxides have potential applications for low-energy hydrogen production and efficient utilization of sunlight.
Radiotherapy of the Hepatocellular Carcinoma in Mice Has a Time-Of-Day-Dependent Impact on the Mouse Hippocampus
Authors: Yassine Mona , Hassan Soha A. , Sommer Simon , Yücel Lea Aylin , Bellert Hanna , Hallenberger Johanna , Sohn Dennis , Korf Horst-Werner , von Gall Charlotte , Ali Amira A. H.
Published: December 2022

Chronic liver diseases including hepatocellular carcinoma (HCC) create a state of chronic inflammation that affects the brain via the liver–brain axis leading to an alteration of neurotransmission and cognition. However, little is known about the effects of HCC on the hippocampus, the key brain region for learning and memory. Moreover, radiotherapy used to treat HCC has severe side effects that impair patients’ life quality. Thus, designing optimal strategies, such as chronotherapy, to enhance the efficacy and reduce the side effects of HCC treatment is critically important. We addressed the effects of HCC and the timed administration of radiotherapy in mice on the expression of pro-inflammatory cytokines, clock genes, markers for glial activation, oxidative stress, neuronal activity and proliferation in the hippocampal neurogenic niche. Our data showed that HCC induced the upregulation of genes encoding for pro-inflammatory cytokines, altered clock gene expressions and reduced proliferation in the hippocampus. Radiotherapy, in particular when applied during the light/inactive phase enhanced all these effects in addition to glial activation, increased oxidative stress, decreased neuronal activity and increased levels of phospho(p)-ERK. Our results suggested an interaction of the circadian molecular clockwork and the brain’s innate immune system as key players in liver–brain crosstalk in HCC and that radiotherapy when applied during the light/inactive phase induced the most profound alterations in the hippocampus.
Targeting PCSK9 in Liver Cancer Cells Triggers Metabolic Exhaustion and Cell Death by Ferroptosis
Authors: Alannan Malak , Fatrouni Hala , Trézéguet Véronique , Dittrich-Domergue Franziska , Moreau Patrick , Siegfried Géraldine , Liet Benjamin , Khatib Abdel-Majid , Grosset Christophe F. , Badran Bassam , Fayyad-Kazan Hussein , Merched Aksam J.
Published: December 2022

Deregulated lipid metabolism is a common feature of liver cancers needed to sustain tumor cell growth and survival. We aim at taking advantage of this vulnerability and rewiring the oncogenic metabolic hub by targeting the key metabolic player pro-protein convertase subtilisin/kexin type 9 (PCSK9). We assessed the effect of PCSK9 inhibition using the three hepatoma cell lines Huh6, Huh7 and HepG2 and validated the results using the zebrafish in vivo model. PCSK9 deficiency led to strong inhibition of cell proliferation in all cell lines. At the lipid metabolic level, PCSK9 inhibition was translated by an increase in intracellular neutral lipids, phospholipids and polyunsaturated fatty acids as well as a higher accumulation of lipid hydroperoxide. Molecular signaling analysis involved the disruption of the sequestome 1/Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 (p62/Keap1/Nrf2) antioxidative axis, leading to ferroptosis, for which morphological features were confirmed by electron and confocal microscopies. The anti-tumoral effects of PCSK9 deficiency were validated using xenograft experiments in zebrafish. The inhibition of PCSK9 was effective in disrupting the oncometabolic process, inducing metabolic exhaustion and enhancing the vulnerability of cancer cells to iron-triggered lipid peroxidation. We provide strong evidence supporting the drug repositioning of anti-PCSK9 approaches to treat liver cancers.
Relationship between Tumor Infiltrating Immune Cells and Tumor Metastasis and Its Prognostic Value in Cancer
Authors: Li Huan-Xiang , Wang Shu-Qi , Lian Zheng-Xing , Deng Shou-Long , Yu Kun
Published: December 2022

Tumor metastasis is an important reason for the difficulty of tumor treatment. Besides the tumor cells themselves, the tumor microenvironment plays an important role in the process of tumor metastasis. Tumor infiltrating immune cells (TIICs) are one of the main components of TME and plays an important role in every link of tumor metastasis. This article mainly reviews the role of tumor-infiltrating immune cells in epithelial mesenchymal transformation, extracellular matrix remodeling, tumor angiogenesis and formation of pre-metastatic niche. The value of TIICs in the prognosis of cervical cancer, lung cancer and breast cancer was also discussed. We believe that accurate prognosis of cancer treatment outcomes is conducive to further improving treatment regimens, determining personalized treatment strategies, and ultimately achieving successful cancer treatment. This paper elucidates the relationship between tumor and TIICs in order to explore the function of immune cells in different diseases and provide new ideas for the treatment of cancer.
Construction of a Necroptosis-Related lncRNA Signature for Predicting Prognosis and Immune Response in Kidney Renal Clear Cell Carcinoma
Authors: Zhang Yue , Zhuang Tongtian , Xin Zhenlong , Sun Changjian , Li Deyang , Ma Nan , Wang Xiaoyan , Wang Xuning
Published: December 2022

Necroptosis is a new type of programmed cell death and involves the occurrence and development of various cancers. Moreover, the aberrantly expressed lncRNA can also affect tumorigenesis, migration, and invasion. However, there are few types of research on the necroptosis-related lncRNA (NRL), especially in kidney renal clear cell carcinoma (KIRC). In this study, we analyzed the sequencing data obtained from the TGCA-KIRC dataset, then applied the LASSO and COX analysis to identify 6 NRLs (AC124854.1, AL117336.1, DLGAP1-AS2, EPB41L4A-DT, HOXA-AS2, and LINC02100) to construct a risk model. Patients suffering from KIRC were divided into high- and low-risk groups according to the risk score, and the patients in the low-risk group had a longer OS. This signature can be used as an indicator to predict the prognosis of KIRC independent of other clinicopathological features. In addition, the gene set enrichment analysis showed that some tumor and immune-associated pathways were more enriched in a high-risk group. We also found significant differences between the high and low-risk groups in the infiltrating immune cells, immune functions, and expression of immune checkpoint molecules. Finally, we use the “pRRophetic” package to complete the drug sensitivity prediction, and the risk score could reflect patients’ response to 8 small molecule compounds. In general, NRLs divided KIRC into two subtypes with different risk scores. Furthermore, this signature based on the 6 NRLs could provide a promising method to predict the prognosis and immune response of KIRC patients. To some extent, our findings helped give a reference for further research between NRLs and KIRC and find more effective therapeutic drugs for KIRC.
Mechanisms of Lung Damage and Development of COPD Due to Household Biomass-Smoke Exposure: Inflammation, Oxidative Stress, MicroRNAs, and Gene Polymorphisms
Authors: Ortiz-Quintero Blanca , Martínez-Espinosa Israel , Pérez-Padilla Rogelio
Published: December 2022

Chronic exposure to indoor biomass smoke from the combustion of solid organic fuels is a major cause of disease burden worldwide. Almost 3 billion people use solid fuels such as wood, charcoal, and crop residues for indoor cooking and heating, accounting for approximately 50% of all households and 90% of rural households globally. Biomass smoke contains many hazardous pollutants, resulting in household air pollution (HAP) exposure that often exceeds international standards. Long-term biomass-smoke exposure is associated with Chronic Obstructive Pulmonary Disease (COPD) in adults, a leading cause of morbidity and mortality worldwide, chronic bronchitis, and other lung conditions. Biomass smoke-associated COPD differs from the best-known cigarette smoke-induced COPD in several aspects, such as a slower decline in lung function, greater airway involvement, and less emphysema, which suggests a different phenotype and pathophysiology. Despite the high burden of biomass-associated COPD, the molecular, genetic, and epigenetic mechanisms underlying its pathogenesis are poorly understood. This review describes the pathogenic mechanisms potentially involved in lung damage, the development of COPD associated with wood-derived smoke exposure, and the influence of genetic and epigenetic factors on the development of this disease.
Genome- and Transcriptome-Wide Association Studies Identify Susceptibility Genes and Pathways for Periodontitis
Authors: Zhu Guirong , Cui Xing , Fan Liwen , Pan Yongchu , Wang Lin
Published: December 2022

Several genes associated with periodontitis have been identified through genome-wide association studies (GWAS); however, known genes only explain a minority of the estimated heritability. We aimed to explore more susceptibility genes and the underlying mechanisms of periodontitis. Firstly, a genome-wide meta-analysis of 38,532 patients and 316,185 healthy controls was performed. Then, cross- and single-tissue transcriptome-wide association studies (TWAS) were conducted based on GWAS summary statistics and the Genotype-Tissue Expression (GTEx) project. Risk genes were evaluated to determine if they were differentially expressed in periodontitis sites compared with unaffected sites using public datasets. Finally, gene co-expression network analysis was conducted to identify the functional biology of the susceptible genes. A total of eight single nucleotide polymorphisms (SNPs) within the introns of lncRNA LINC02141 approached genome-wide significance after meta-analysis. EZH1 was identified as a novel susceptibility gene for periodontitis by TWAS and was significantly upregulated in periodontitis-affected gingival tissues. EZH1 co-expression genes were greatly enriched in the cell-substrate junction, focal adhesion and other important pathways. Our findings may offer a fundamental clue for comprehending the genetic mechanisms of periodontitis.
PNPLA3(I148M) Inhibits Lipolysis by Perilipin-5-Dependent Competition with ATGL
Authors: Witzel Hagen Roland , Schwittai Inga Maria Gertrud , Hartmann Nils , Mueller Sebastian , Schattenberg Jörn M. , Gong Xue-Min , Backs Johannes , Schirmacher Peter , Schuppan Detlef , Roth Wilfried , Straub Beate Katharina
Published: December 2022

The single nucleotide polymorphism I148M of the lipase patatin-like phospholipase domain containing 3 (PNPLA3) is associated with an unfavorable prognosis in alcoholic and non-alcoholic steatohepatitis (ASH, NASH), with progression to liver cirrhosis and development of hepatocellular carcinoma. In this study, we investigated the mechanistic interaction of PNPLA3 with lipid droplet (LD)-associated proteins of the perilipin family, which serve as gatekeepers for LD degradation. In a collective of 106 NASH, ASH and control liver samples, immunohistochemical analyses revealed increased ballooning, inflammation and fibrosis, as well as an accumulation of PNPLA3–perilipin 5 complexes on larger LDs in patients homo- and heterozygous for PNPLA3(I148M). Co-immunoprecipitation demonstrated an interaction of PNPLA3 with perilipin 5 and the key enzyme of lipolysis, adipose triglyceride lipase (ATGL). Localization studies in cell cultures and human liver showed colocalization of perilipin 5, ATGL and PNPLA3. Moreover, the lipolytic activity of ATGL was negatively regulated by PNPLA3 and perilipin 5, whereas perilipin 1 displaced PNPLA3 from the ATGL complex. Furthermore, ballooned hepatocytes, the hallmark of steatohepatitis, were positive for PNPLA3 and perilipins 2 and 5, but showed decreased perilipin 1 expression with respect to neighboured hepatocytes. In summary, PNPLA3- and ATGL-driven lipolysis is significantly regulated by perilipin 1 and 5 in steatohepatitis.
Characterizing Relevant MicroRNA Editing Sites in Parkinson’s Disease
Authors: Lu Chenyu , Ren Shuchao , Xie Wenping , Zhao Zhigang , Wu Xingwang , Guo Shiyong , Suo Angbaji , Zhou Nan , Yang Jun , Wu Shuai , Zheng Yun
Published: December 2022

MicroRNAs (miRNAs) are extensively edited in human brains. However, the functional relevance of the miRNA editome is largely unknown in Parkinson’s disease (PD). By analyzing small RNA sequencing profiles of brain tissues of 43 PD patients and 88 normal controls, we found that the editing levels of five A-to-I and two C-to-U editing sites are significantly correlated with the ages of normal controls, which is disrupted in PD patients. We totally identified 362 miRNA editing sites with significantly different editing levels in prefrontal cortices of PD patients (PD-PC) compared to results of normal controls. We experimentally validated that A-to-I edited miR-497-5p, with significantly higher expression levels in PD-PC compared to normal controls, directly represses OPA1 and VAPB. Furthermore, overexpression of A-to-I edited miR-497-5p downregulates OPA1 and VAPB in two cell lines, and inhibits proliferation of glioma cells. These results suggest that the hyperediting of miR-497-5p in PD contributes to enhanced progressive neurodegeneration of PD patients. Our results provide new insights into the mechanistic understanding, novel diagnostics, and therapeutic clues of PD.
Multiformin-Type Azaphilones Prevent SARS-CoV-2 Binding to ACE2 Receptor
Authors: Jansen-Olliges Linda , Chatterjee Shambhabi , Jia Lili , Stahl Frank , Bär Christian , Stadler Marc , Surup Frank , Zeilinger Carsten
Published: December 2022

Protein microarray screenings identified fungal natural products from the azaphilone family as potent inhibitors of SARS-CoV-2 spike protein binding to host ACE2 receptors. Cohaerin F, as the most potent substance from the cohaerin group, led to more than 50% less binding of ACE2 and SARS-CoV-2 spike protein. A survey for structurally related azaphilones yielded the structure elucidation of six new multiformins E–J (10–15) and the revision of the stereochemistry of the multiformins. Cohaerin and multiformin azaphilones (1–5, 8, 12) were assessed for their activity in a cell-based infection assay. Calu-3 cells expressing human ACE2 receptor showed more than 75% and 50% less infection by SARS-CoV-2 pseudotyped lentivirus particles after treatment with cohaerin C (1) and cohaerin F (4), respectively. Multiformin C (8) and G (12) that nearly abolished the infection of cells. Our data show that multiformin-type azaphilones prevent the binding of SARS-CoV-2 to the cell entry receptor ACE2.