bluuebunny/crossref_metadata_2025 huggingface dataset:
The Influence of the Ketogenic Diet on the Immune Tolerant Microenvironment in Glioblastoma
Authors: Kesarwani Pravin , Kant Shiva , Zhao Yi , Miller C. Ryan , Chinnaiyan Prakash
Published: November 2022

Glioblastoma (GBM) represents an aggressive and immune-resistant cancer. Preclinical investigations have identified anti-tumor activity of a ketogenic diet (KD) potentially being used to target GBM’s glycolytic phenotype. Since immune cells in the microenvironment have a similar reliance upon nutrients to perform their individual functions, we sought to determine if KD influenced the immune landscape of GBM. Consistent with previous publications, KD improved survival in GBM in an immune-competent murine model. Immunophenotyping of tumors identified KD-influenced macrophage polarization, with a paradoxical 50% increase in immune-suppressive M2-like-macrophages and a decrease in pro-inflammatory M1-like-macrophages. We recapitulated KD in vitro using a modified cell culture based on metabolomic profiling of serum in KD-fed mice, mechanistically linking the observed changes in macrophage polarization to PPARγ-activation. We hypothesized that parallel increases in M2-macrophage polarization tempered the therapeutic benefit of KD in GBM. To test this, we performed investigations combining KD with the CSF-1R inhibitor (BLZ945), which influences macrophage polarization. The combination demonstrated a striking improvement in survival and correlative studies confirmed BLZ945 normalized KD-induced changes in macrophage polarization. Overall, KD demonstrates antitumor activity in GBM; however, its efficacy is attenuated by promoting an immunosuppressive phenotype in macrophages. Combinatorial strategies designed to modulate macrophage polarization represent a rational approach to improve the anti-tumor activity of KD in GBM.
Extracellular Heparan 6-O-Endosulfatases SULF1 and SULF2 in Head and Neck Squamous Cell Carcinoma and Other Malignancies
Authors: Yang Yang , Ahn Jaeil , Edwards Nathan J. , Benicky Julius , Rozeboom Aaron M. , Davidson Bruce , Karamboulas Christina , Nixon Kevin C. J. , Ailles Laurie , Goldman Radoslav
Published: November 2022

Pan-cancer analysis of TCGA and CPTAC (proteomics) data shows that SULF1 and SULF2 are oncogenic in a number of human malignancies and associated with poor survival outcomes. Our studies document a consistent upregulation of SULF1 and SULF2 in HNSC which is associated with poor survival outcomes. These heparan sulfate editing enzymes were considered largely functional redundant but single-cell RNAseq (scRNAseq) shows that SULF1 is secreted by cancer-associated fibroblasts in contrast to the SULF2 derived from tumor cells. Our RNAScope and patient-derived xenograft (PDX) analysis of the HNSC tissues fully confirm the stromal source of SULF1 and explain the uniform impact of this enzyme on the biology of multiple malignancies. In summary, SULF2 expression increases in multiple malignancies but less consistently than SULF1, which uniformly increases in the tumor tissues and negatively impacts survival in several types of cancer even though its expression in cancer cells is low. This paradigm is common to multiple malignancies and suggests a potential for diagnostic and therapeutic targeting of the heparan sulfatases in cancer diseases.
Comorbidities and Risk Factors of Patients Diagnosed with CRC after Positive Fecal Test in Real Life
Authors: Abu-Freha Naim , Gouldner Rachel , Cohen Bracha , Gordon Michal , Sagi Orly , Taha Gadeer , Ben Shoshan Liza , Levi Zohar
Published: November 2022

(1) Background: Fecal occult blood test (FOBT) is the modality of choice in most countries for colorectal cancer (CRC) screening. We aimed to investigate the risk factors for CRC among patients with a positive FOBT in real life. (2) Methods: This was a retrospective study that included patients who tested positive for FOBT. Data regarding the comorbidities and laboratories were collected and compared between CRC and non-CRC groups. (3) Results: Positive FOBT was found among 45,500 (5.36%) subjects and CRC was found in 1502 (3.3%). CRC patients were older, age 62.7 ± 7.15 years compared with 59.33 ± 7.3 years (p < 0.001), and had significantly higher rates of hypertension (48.4% vs. 44.7%, p = 0.002), iron-deficiency anemia (20.6% vs. 16.4, p < 0.001), family history of CRC (7.3% vs. 5.1%, p < 0.001), and previous CRC (6.5% vs. 0.3%, p < 0.001). Lower levels of hemoglobin, iron, and ferritin were found in the CRC group. Age, family history of CRC, and previous CRC were found to be significant risk factors for diagnosis of CRC after positive FOBT with OR of 1.057, 1.4, and 15.9, respectively. (4) Conclusions: Iron-deficiency anemia, family history of CRC, previous colorectal cancer, and low hemoglobin, iron, and ferritin levels should direct physicians to give high priority to colonoscopy scheduling.
Should We Always Perform Preoperative Chest Computed Tomography in Patients with cT1a Renal Cell Carcinoma?
Authors: Chung Jae-Wook , Kang Jun-Koo , Jang Se Won , Lee Eun Hye , Chun So Young , Choi Seock Hwan , Lee Jun Nyung , Kim Bum Soo , Kim Hyun Tae , Kim See Hyung , Kim Tae-Hwan , Yoo Eun Sang , Kwon Tae Gyun , Park Dong Jin , Ha Yun-Sok
Published: November 2022

No definitive criteria regarding the performance of preoperative chest computed tomography (CT) in patients with cT1a renal cell carcinoma (RCC) exists. We aimed to establish an objective standard for the optimal timing of preoperative chest CT in patients with RCC. Data from 890 patients who underwent surgical treatment for RCC between January 2011 and December 2020 were retrospectively collected. The primary endpoint was detection of lung metastasis on chest CT before nephrectomy. A multivariable logistic regression model predicting positive chest CT scans was used. Predictors included preoperative cTN stage, presence of systemic symptoms, Charlson comorbidity index (CCI), platelet count/hemoglobin ratio, albumin/globulin ratio (AGR), and De Ritis ratio. The overall rate of positive chest CT scans before nephrectomy was 3.03% (27/890). Only one patient had lung metastasis before surgery for cT1a. cT stage (≥cT1b), CCI ≥4, and low AGR were associated with a higher risk of positive chest CT scans. The best cutoff value for AGR was 1.39. After 890-sample bootstrap validation, the concordance index was 0.80. The net benefit of the proposed strategy was superior to that of the select-all and select-none strategies according to decision curve analysis. Therefore, when chest CT scans were performed with a risk of a positive result ≥10%, 532 (59.8%) negative chest CT scans could be prevented. Only 24 (2.7%) potentially positive chest CT scans were misdiagnosed. Therefore, we recommend chest CT in patients with ≥cT1b disease, CCI ≥4, and low AGR.
Development and Validation of Novel Deep-Learning Models Using Multiple Data Types for Lung Cancer Survival
Authors: Hsu Jason C. , Nguyen Phung-Anh , Phuc Phan Thanh , Lo Tsai-Chih , Hsu Min-Huei , Hsieh Min-Shu , Le Nguyen Quoc Khanh , Cheng Chi-Tsun , Chang Tzu-Hao , Chen Cheng-Yu
Published: November 2022

A well-established lung-cancer-survival-prediction model that relies on multiple data types, multiple novel machine-learning algorithms, and external testing is absent in the literature. This study aims to address this gap and determine the critical factors of lung cancer survival. We selected non-small-cell lung cancer patients from a retrospective dataset of the Taipei Medical University Clinical Research Database and Taiwan Cancer Registry between January 2008 and December 2018. All patients were monitored from the index date of cancer diagnosis until the event of death. Variables, including demographics, comorbidities, medications, laboratories, and patient gene tests, were used. Nine machine-learning algorithms with various modes were used. The performance of the algorithms was measured by the area under the receiver operating characteristic curve (AUC). In total, 3714 patients were included. The best performance of the artificial neural network (ANN) model was achieved when integrating all variables with the AUC, accuracy, precision, recall, and F1-score of 0.89, 0.82, 0.91, 0.75, and 0.65, respectively. The most important features were cancer stage, cancer size, age of diagnosis, smoking, drinking status, EGFR gene, and body mass index. Overall, the ANN model improved predictive performance when integrating different data types.
Chondroitin Sulfate Proteoglycan 4 as a Marker for Aggressive Squamous Cell Carcinoma
Authors: Chen Kathryn , Yong Joel , Zauner Roland , Wally Verena , Whitelock John , Sajinovic Mila , Kopecki Zlatko , Liang Kang , Scott Kieran Francis , Mellick Albert Sleiman
Published: November 2022

Chondroitin sulfate (CS) proteoglycan 4 (CSPG4) is a cell surface proteoglycan that is currently under investigation as a marker of cancer malignancy, and as a potential target of anticancer drug treatment. CSPG4 acts as a driver of tumourigenesis by regulating turnover of the extracellular matrix (ECM) to promote tumour cell invasion, migration as well as inflammation and angiogenesis. While CSPG4 has been widely studied in certain malignancies, such as melanoma, evidence is emerging from global gene expression studies, which suggests a role for CSPG4 in squamous cell carcinoma (SCC). While relatively treatable, lack of widely agreed upon diagnostic markers for SCCs is problematic, especially for clinicians managing certain patients, including those who are aged or infirm, as well as those with underlying conditions such as epidermolysis bullosa (EB), for which a delayed diagnosis is likely lethal. In this review, we have discussed the structure of CSPG4, and quantitatively analysed CSPG4 expression in the tissues and pathologies where it has been identified to determine the usefulness of CSPG4 expression as a diagnostic marker and therapeutic target in management of malignant SCC.
Performance and Prospects of [68Ga]Ga-FAPI PET/CT Scans in Lung Cancer
Authors: Borgonje Paula E. , Andrews Louise M. , Herder Gerarda J. M. , de Klerk John M. H.
Published: November 2022

Fibroblast activation protein (FAP) could be a promising target for tumor imaging and therapy, as it is expressed in >90% of epithelial cancers. A high level of FAP-expression might be associated with worse prognosis in several cancer types, including lung cancer. FAPI binds this protein and allows for labelling to Gallium-68, as well as several therapeutic radiopharmaceuticals. As FAP is only expressed at insignificant levels in adult normal tissue, FAPI provides a highly specific tumor-marker for many epithelial cancers. In this review, current information on the use of [68Ga]Ga-FAPI PET/CT in lung cancer is presented. [68Ga]Ga-FAPI shows a high uptake (standardized uptake value = SUVmax) and tumor-to-background ratio (TBR) in primary lung cancer lesions, as well as in metastatic lesions of other tumor types located in the lung and in lung cancer metastases located throughout the body. Where a comparison was made to [18F]FDG PET/CT, [68Ga]Ga-FAPI showed a similar or higher SUVmax and TBR. In brain and bone metastases, [68Ga]Ga-FAPI PET/CT outperformed [18F]FDG PET/CT. In addition to this strong diagnostic performance, a possible prognostic value of [68Ga]Ga-FAPI PET/CT in lung cancer is proposed.
Evaluating Different Quantitative Shear Wave Parameters of Ultrasound Elastography in the Diagnosis of Lymph Node Malignancies: A Systematic Review and Meta-Analysis
Authors: Gao Yujia , Zhao Yi , Choi Sunyoung , Chaurasia Anjalee , Ding Hao , Haroon Athar , Wan Simon , Adeleke Sola
Published: November 2022

Shear wave elastography (SWE) has shown promise in distinguishing lymph node malignancies. However, the diagnostic accuracies of various SWE parameters that quantify tissue stiffness are yet to be demonstrated. To evaluate the pooled diagnostic accuracy of different SWE parameters for differentiating lymph node malignancies, we conducted a systematic screening of four databases using the PRISMA guidelines. Lymph node biopsy was adopted as the reference standard. Emax (maximum stiffness), Emean (mean stiffness), Emin (minimum stiffness), and Esd (standard deviation) SWE parameters were subjected to separate meta-analyses. A sub-group analysis comparing the use of Emax in cervical (including thyroid) and axillary lymph node malignancies was also conducted. Sixteen studies were included in this meta-analysis. Emax and Esd demonstrated the highest pooled sensitivity (0.78 (95% CI: 0.69–0.87); 0.78 (95% CI: 0.68–0.87)), while Emean demonstrated the highest pooled specificity (0.93 (95% CI: 0.88–0.98)). From the sub-group analysis, the diagnostic performance did not differ significantly in cervical and axillary LN malignancies. In conclusion, SWE is a promising adjunct imaging technique to conventional ultrasonography in the diagnosis of lymph node malignancy. SWE parameters of Emax and Esd have been identified as better choices of parameters for screening clinical purposes.
Comparison of Two 2.45 GHz Microwave Ablation Devices with Respect to Ablation Zone Volume in Relation to Applied Energy in Patients with Malignant Liver Tumours
Authors: Ruiter Simeon J. S. , de Jong Jamila E. , Pennings Jan Pieter , de Haas Robbert J. , de Jong Koert P.
Published: November 2022

Purpose: (i) to compare two 2.45 GHz MWA devices with respect to AZV in relation to the applied energy after MWA in patients with hepatocellular carcinoma (HCC) or colorectal liver metastasis (CRLM) and (ii) to identify potential confounders for this relationship. Methods: In total, 102 tumours, 65 CRLM and 37 HCC were included in this retrospective analysis. Tumours were treated with Emprint (n = 71) or Neuwave (n = 31) MWA devices. Ablation treatment setting were recorded and applied energy was calculated. AZV and tumour volumes were segmented on the contrast-enhanced CT scans obtained 1 week after treatment. The AZV to applied energy R(AZV:E) ratios were calculated for each tumour treatment and compared between both MWA devices and tumour types. Results: R(AZV:E)EMPRINT was 0.41 and R(AZV:E)NEUWAVE was 0.81, p < 0.001. Moderate correlation between AZV and applied energy was found for Emprint (r = 0.57, R2 = 0.32, p < 0.001) and strong correlation was found for Neuwave (r = 0.78, R2 = 0.61, p < 0.001). R(AZV:E)CRLM was 0.45 and R(AZV:E)HCC was 0.52, p = 0.270. Conclusion: This study confirms the unpredictability of AZVs based on the applied output energy for HCC and CRLM. No significant differences in R(AZV:E) were observed between CRLM and HCC. Significantly lower R(AZV:E) was found for Emprint devices compared to Neuwave; however, reflected energy due to cable and antenna design remains unclear and might contribute to these differences.
Polygenic Risk Scores Associated with Tumor Immune Infiltration in Common Cancers
Authors: Choi Jungyoon , Kim Jung Sun , Sung Hwa Jung , Chen Yu-Wei , Chen Zhishan , Wen Wanqing , Shu Xiao-ou , Guo Xingyi
Published: November 2022

It is largely unknown whether genetic susceptibility contributes to tumor immune infiltration in common cancers. We systematically investigated the association between polygenic risk scores (PRSs) and tumor immune infiltration in common cancers. First, we constructed a PRS for common cancers using the risk variants identified in previous genome-wide association studies. Then, we analyzed 139 immune traits predicted by previous studies by examining gene expression data in tumor tissues from The Cancer Genome Atlas (TCGA). We applied regression analyses to evaluate the associations between PRS and immune traits for each cancer overall and stratified by stage, including 2160 pathologically confirmed cases of breast, colorectal, lung, ovarian, pancreatic, and prostate cancers in the White population. At a nominal (p < 0.05) significance level, we identified 31 significant associations between PRS and immune traits. In the analyses stratified by stage for breast, colorectal, lung adenocarcinoma, and lung squamous cell carcinoma, we identified 65 significant associations, including 56 associations that were undetected by the overall analysis. This study provides evidence for genetic risk factors affecting immune infiltration and provides novel insights into the role of genetic susceptibility in immune responses, underlying cancer development, prognosis, and the potential role of an early diagnostic or therapeutic targeting strategy.
Construction of Oxidative Stress-Related Genes Risk Model Predicts the Prognosis of Uterine Corpus Endometrial Cancer Patients
Authors: Liu Qin , Yu Minghua , Zhang Tao
Published: November 2022

Oxidative stress contributes significantly to cancer development. Recent studies have demonstrated that oxidative stress could alter the epigenome and, in particular, DNA methylation. This study aimed to explore the potential link between oxidative stress and uterine corpus endometrial carcinoma (UCEC). An analysis of RNA-seq data and relevant clinical information was conducted with data from The Cancer Genome Atlas (TCGA), and oxidative stress genes were obtained from Gene Set Enrichment Analysis (GSEA). Differentially expressed genes (DEGs) in normal and tumor groups of UCEC were analyzed using GO and KEGG enrichment analysis. As a result of survival analysis, Lasso regression analysis of DEGs, a risk score model of oxidative stress-related genes (OSRGs) was constructed. Moreover, this study demonstrated that OSRGs are associated with immune cell infiltration in UCEC, suggesting oxidative stress may play a role in UCEC development by activating immune cells. We discovered 136 oxidative stress-related DEGs in UCEC, from which we screened 25 prognostic genes significantly related to the overall survival of UCEC patients. BCL2A1, CASP6, GPX2, HIC1, IL19, MSX1, RNF183, SFN, TRPM2 and HIST1H3C are associated with a good prognosis while CDKN2A, CHAC1, E2F1, GSDME, HMGA1, ITGA7, MCM4, MYBL2, PPIF, S100A1, S100A9, STK26 and TRIB3 are involved in a poor prognosis in UCEC. A 7-OSRGs-based risk score (H3C1, CDKN2A, STK26, TRPM2, E2F1, CHAC1, MSX1) was generated by Lasso regression. Further, an association was found between H3C1, CDKN2A, STK26, TRPM2, E2F1, CHAC1 and MSX1 expression levels and the immune infiltrating cells, including CD8 T cells, NK cells, and mast cells in UCEC. NFYA and RFX5 were speculated as common transcription factors of CDKN2A, TRPM2, E2F1, CHAC1, and MSX1 in UCEC.
Expression Pattern and Prognostic Value of CTLA-4, CD86, and Tumor-Infiltrating Lymphocytes in Rectal Cancer after Neoadjuvant Chemo(radio)therapy
Authors: Yin Xin-Ke , Wang Chao , Feng Li-Li , Bai Shao-Mei , Feng Wei-Xing , Ouyang Neng-Tai , Chu Zhong-Hua , Fan Xin-Juan , Qin Qi-Yuan
Published: November 2022

The synergistic effect of combining immune checkpoint inhibitors (ICIs) with neoadjuvant chemo(radio)therapy (nCRT) in colorectal cancer is still limited. We aimed to understand the impact of nCRT on the tumor microenvironment and to explore favorable immune markers of this combination. Herein, we investigated the expression of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), CD86, CD4, and CD8 after nCRT and its association with clinicopathological characteristics. Immunostaining of immune-related molecules was performed in 255 surgically resected specimens from rectal cancer patients treated with nCRT. CD4 and CD8 expression on the tumor (tCD4/CD8), stroma (sCD4/CD8), and invasive front (iCD4/CD8) was evaluated. The expression levels of immune-related molecules were significantly lower in the nCRT-treated group, except for CTLA-4 and sCD8. However, patients with higher sCD8+ cell density and CTLA-4 expression had better progression-free survival (PFS) and distant metastasis-free survival (DMFS). In addition, higher CD86 expression was associated with poorer overall survival (OS). Higher CTLA-4 expression was associated with higher tCD8+ cell density, whereas CD86 expression was correlated with the cell density of t/sCD8. Prognostic analysis confirmed that the relationships between CTLA-4 and DMFS as well as CD86 and OS were significantly correlated in low rather than high CD8+ cell density. Further the combination of CD8+ cell density and CD86 expression was shown to be an independent prognostic factor of OS, whereas the combination of CTLA-4 was not for DMFS. Together, these results demonstrate significant correlations between CD86 expression and t/sCD8+ cell density in rectal cancer after nCRT and could potentially have clinical implications for combining ICIs and nCRT.
A Critical Review of the Use of Bismuth Halide Perovskites for CO2 Photoreduction: Stability Challenges and Strategies Implemented
Authors: Luévano-Hipólito Edith , Quintero-Lizárraga Oscar L. , Torres-Martínez Leticia M.
Published: November 2022

Inspired by natural photosynthesis, the photocatalytic CO2 reduction reaction (CO2RR) stands as a viable strategy for the production of solar fuels to mitigate the high dependence on highly polluting fossil fuels, as well as to decrease the CO2 concentration in the atmosphere. The design of photocatalytic materials is crucial to ensure high efficiency of the CO2RR process. So far, perovskite materials have shown high efficiency and selectivity in CO2RR to generate different solar fuels. Particularly, bismuth halide perovskites have gained much attention due to their higher absorption coefficients, their more efficient charge transfer (compared to oxide perovskites), and their required thermodynamic potential for CO2RR. Moreover, these materials represent a promising alternative to the highly polluting lead halide perovskites. However, despite all the remarkable advantages of bismuth halide perovskites, their use has been limited, owing to instability concerns. As a consequence, recent reports have offered solutions to obtain structures highly stable against oxygen, water, and light, promoting the formation of solar fuels with promising efficiency for CO2RR. Thus, this review analyzes the current state of the art in this field, particularly studies about stability strategies from intrinsic and extrinsic standpoints. Lastly, we discuss the challenges and opportunities in designing stable bismuth halide perovskites, which open new opportunities for scaling up the CO2RR.
Optimization of SnPd Shell Configuration to Boost ORR Performance of Pt-Clusters Decorated CoOx@SnPd Core-Shell Nanocatalyst
Authors: Cheng Mingxing , Bhalothia Dinesh , Yeh Wei , Beniwal Amisha , Yan Che , Wang Kuan-Wen , Chen Po-Chun , Tu Xin , Chen Tsan-Yao
Published: November 2022

Fuel cells are expected to bring change to the whole human race when commercialized, however, the sluggish kinetics of oxygen reduction reaction (ORR) severely hampers their commercial viability. Thus far, platinum (Pt) based catalysts are nearly inevitable due to the harsh redox environment of fuel cells. Thus, minimizing Pt metal loading and increasing Pt utilization is a paramount factor for realizing fuel cell technologies. In this context, herein, we developed a multi-metallic nanocatalyst (NC) comprising Pt-clusters (1 wt.%) decorated SnPd composite shell over cobalt-oxide core crystal underneath (denoted as CSPP). For optimizing the ORR performance of the as-prepared NC, we further modulated the configuration of the SnPd shell. In the optimum case, when the Sn/Pd ratio is 0.5 (denoted as CSPP 1005), the ORR mass activity (MA) is 3034.7 mA mgPt−1 at 0.85 V vs. RHE in 0.1 M KOH electrolyte, which is 45-times higher than the commercial Johnson Matthey-Pt/C (J.M.-Pt/C; 20 wt.% Pt) catalyst (67 mA mgPt−1). The results of physical inspections along with electrochemical analysis suggest that such high performance of CSPP 1005 NC can be attributed to the synergistic collaboration between Pt-clusters, PtPd nanoalloys, and adjacent SnPd domains, where Pt-clusters and PtPd nanoalloys promote the O2 adsorption and subsequent splitting, while the SnPd shell favours the OH− relocation step. We believe that the obtained results will open a new avenue for further exploring the high-performance Pt-based catalysts with low Pt-loading and high utilization.
Improved Catalytic Performance of Lipase Eversa® Transform 2.0 via Immobilization for the Sustainable Production of Flavor Esters—Adsorption Process and Environmental Assessment Studies
Authors: Miguel Júnior José , Mattos Fernanda R. , Costa Guilherme R. , Zurlo Ana B. R. , Fernandez-Lafuente Roberto , Mendes Adriano A.
Published: November 2022

The aim of this study was to produce several flavor esters via esterification of octanoic acid with different commercial short-chain alcohols (methanol, propanol, isoamyl alcohol, hexanol and benzyl alcohol) and fusel oil in solvent-free systems. Lipase Eversa® Transform 2.0 immobilized via mechanism of interfacial activation on poly(styrenene-divinylbenzene) (PSty-DVB) beads was used as heterogeneous biocatalyst and its catalytic performance was compared with that of the soluble lipase. The heterogeneous biocatalyst was prepared by employing 5 mmol·L−1 buffer sodium acetate at pH 5.0 and 25 °C using an initial protein loading of 40 mg·g−1. The maximum amount of immobilized protein reached was 31 mg·g−1, corresponding to an immobilization yield of 80%. Mass transfer studies demonstrated that the lipase was preferentially adsorbed inside the pores of the support, which was confirmed by scanning electron microscopy analysis. Lipase immobilization can be described by a pseudo-first-order kinetic model via a physisorption process. When used as biocatalysts of the target reactions, the highest conversion percentage (between 65% and 85% of acid conversion after 60–90 min of reaction) values were achieved for esterification reactions catalyzed by immobilized lipase. Reusability tests revealed high retention of the original activity of the immobilized lipase after six successive batch reactions using isoamyl alcohol (47%) and fusel oil (72%). The proposed reaction systems can be considered green processes (EcoScale score above 80), with exception of methanol medium, classified as an acceptable green process (EcoScale score of 68). These results show that the heterogeneous biocatalyst prepared can be an economic and sustainable option for flavor esters production on an industrial scale.
Facile Preparation and Promising Hydrothermal Stability of Spherical γ-Alumina Support with High Specific Surface Area
Authors: Zhang Yi , Lv Yimin , Mo Yufan , Li Huiyu , Tang Pinggui , Li Dianqing , Feng Yongjun
Published: November 2022

It is of great importance to develop a spherical γ-alumina support with high hydrothermal stability to be used in platinum reforming catalyst processes. The porous pseudo-boehmite powder with a high surface area was first synthesized via a simple separate nucleation and aging steps method, and was then used as a precursor to produce a spherical γ-Al2O3 support via an oil–ammonia column method. The as-synthesized pseudo-boehmite has a substantially greater specific surface area of 336.0 m2·g−1 in comparison with the commercial Sasol boehmite powder (293.0 m2·g−1) from Sasol Chemicals. In addition, the as-prepared spherical γ-Al2O3 support derived from the as-synthesized pseudo-boehmite also possesses a higher specific surface area of 280.0 m2·g−1 compared to the corresponding Sasol sample. Moreover, the as-prepared spherical γ-Al2O3 balls demonstrate a much higher specific surface area of 185.0 m2·g−1 compared with the Sasol sample of 142.0 m2·g−1 after hydrothermal tests at 600 °C, suggesting its promising application in the chemical industry.
ZrO2-Based Photocatalysts for Wastewater Treatment: From Novel Modification Strategies to Mechanistic Insights
Authors: Rani Vandna , Sharma Amit , Kumar Abhinandan , Singh Pardeep , Thakur Sourbh , Singh Archana , Le Quyet Van , Nguyen Van Huy , Raizada Pankaj
Published: November 2022

Zirconium dioxide (ZrO2) has garnered substantial research interest in the field of photocatalytic water treatment due to its appealing properties, such as thermal stability, considerable physical strength, and strong chemical resistance. However, the wide bandgap energy endorses less photoabsorption and rapid charge carrier recombination kinetics, thus restricting the photoactivity of ZrO2. Previously, vast research efforts have been made to improve the photoefficacy of ZrO2, and hence it is worth exploring the potential strategic modifications responsible for incremented photocatalytic efficiency. In this regard, the present review article emphasizes the optical, structural, and electronic features of ZrO2, which makes it an interesting photocatalytic material. The exceptional modification strategies that help to modulate the crystal structure, morphology, bandgap energy, and charge carrier kinetics are primarily discussed. The potential synthetic routes involving bottom-up and top-down methods are also outlined for understanding the rationale for incorporating these techniques. Moreover, the photocatalytic performance evaluation was done by investigating the photodegradation kinetics of various organic and inorganic pollutants degradation by ZrO2. Conclusively, in light of research advances involving ZrO2 photocatalyst, this review article may expedite further investigation for enhancing the large-scale photocatalytic applications for environmental and energy concerns.
Morphology Effects on Structure-Activity Relationship of Pd/Y-ZrO2 Catalysts for Methane Oxidation
Authors: Zhang Xiujuan , Zheng Tingting , Ma Jiangli , Wang Chengxiong , Yang Dongxia , Ning Ping
Published: November 2022

Pd/Y-ZrO2 catalysts were prepared by Y-ZrO2 with different morphologies (flower-like, spherical, reticulated, and bulk-specific morphology), which were prepared by hydrothermal synthesis. Activity evaluation and characterization results show that the morphology influences the microstructures of Y-ZrO2 and the chemical states of active Pd species, thus affecting the activity of methane oxidation. Bulk Pd/Y-ZrO2 exhibits the best CH4 oxidation activity and thermal stability due to the block shape exposed (101) surface, and the single tetragonal phase structure maintained after high-temperature aging. The relatively large-sized Pd particles and Pd0 jointly promote the catalytic oxidation of CH4.
Electrochemical Activity of Original and Infiltrated Fe-Doped Ba(Ce,Zr,Y)O3-Based Electrodes to Be Used for Protonic Ceramic Fuel Cells
Authors: Tarutina Liana R. , Kasyanova Anna V. , Starostin George N. , Vdovin Gennady K. , Medvedev Dmitry A.
Published: November 2022

Proton-ceramic fuel cells (PCFCs) are promising devices for electrochemical energy conversion purposes due to their combination of high energy efficiency, environmental friendliness, and high durability. In the present work, the polarization characteristics of promising electrodes for PCFCs based on BaFexCe0.7−xZr0.2Y0.1O3−δ (BCZYFx) are comprehensively studied. Along with the individual BCZYFx electrodes, we investigated a method for improving their electrochemical activity by introducing nanoparticles of PrOx electrocatalysts into the porous structure of the electrode material. According to the experimental data, electroactivation allowed for the polarization resistances of the electrodes at 700 °C to be reduced from 1.16, 0.27, 0.62 Ω°cm2 to 0.09, 0.13, 0.43 Ω°cm2 for x = 0.5, 0.6, and 0.7, respectively. For a PCFC cell with an air electrode of BCZYF0.6 composition activated using PrOx nanoparticles, it was possible to achieve a maximum specific power of 300 mW cm−2 at 750 °C, which is competitive for a single cell with Co-free cathodes. The results obtained provide insight into the processes occurring in the studied electrodes after electroactivation. It is shown how the improvement of electrochemical characteristics of the electrode can be realized by a simple infiltration method in combination with a subsequent thermal treatment.
Construction and Synthesis of MoS2/Biocarbon Composites for Efficient Visible Light-Driven Catalytic Degradation of Humic Acid
Authors: Wang Chencheng , Wang Ning , Ni Huicheng , Yao Congcong , Qian Junchao , Wei Jianqiang , Chen Jianping , Wu Zhiren
Published: November 2022

MoS2/bio-template carbon composite materials with outstanding photocatalytic degradation performance were constructed and synthesized by an impregnation–hydrothermal–calcination (IHC) method. Composites of the same type were synthesized by a direct-impregnation–calcination (DIC) method for comparison. The results showed that calcination process was obtained from biotemplate carbon with preserved structure. IHC method obtained petal-like MoS2, while DIC method obtained needle-like MoS2. The composite material exhibits adsorption–catalytic degradation performance. Driven by visible light, the photocatalytic degradation efficiency of the composites synthesized by IHC method for humic acid reached 98.73% after 150 min of illumination.
3-D/3-D Z-Scheme Heterojunction Composite Formed by Marimo-like Bi2WO6 and Mammillaria-like ZnO for Expeditious Sunlight Photodegradation of Dimethyl Phthalate
Authors: Chin Ying-Hui , Sin Jin-Chung , Lam Sze-Mun , Zeng Honghu , Lin Hua , Li Haixiang , Huang Liangliang , Mohamed Abdul Rahman
Published: November 2022

In the present work, we assessed the photocatalytic performance of the new 3-D/3-D Z-scheme heterojunction composite for the degradation of dimethyl phthalate (DMP). The composite was composed by marimo-like Bi2WO6 and mammillaria-like ZnO which was named BWZ. The composite was successfully fabricated using a hydrothermal-precipitation method and analyzed via different characterization techniques. Under natural sunlight irradiation, the optimal composite with 20 wt% of Bi2WO6/ZnO (20-BWZ) exhibited a photodegradation rate constant of 0.0259 min−1, which reached 2.3 and 5.9-folds greater than those of pure ZnO (0.0112 min−1) and Bi2WO6 (0.0044 min−1), respectively. That was predominantly attributed to the formation of a Z-scheme photocatalytic system in the as-synthesized composite reduced the charge carrier recombination and accelerated the photoactivity. Transient photocurrent response and electrochemical impedance spectroscopy analyses were performed to confirm this conclusion. The reusability test indicated that the 20-BWZ had no significant deactivation after four runs, which inferred good stability of the as-prepared composite. Furthermore, the quenching test demonstrated that the photogenerated hole, superoxide anion radical and hydroxyl radical were all involved in the photodegradation of DMP, among which •OH was the principal reactive species. This work revealed that the as-prepared BWZ composites have great potential applications for the degradation of refractory pollutants in the environmental remediation field.
Correction: Mao et al. Controllable Construction of IrCo Nanoclusters and the Performance for Water Electrolysis. Catalysts 2022, 12, 914
Authors: Mao Fangqin , Zhao Xiaojie , Chang Ying , Jia Jingchun
Published: November 2022

The authors wish to make the following corrections to this paper [...]
Chromosome Inequality: Causes and Consequences of Non-Random Segregation Errors in Mitosis and Meiosis
Authors: Klaasen Sjoerd J. , Kops Geert J. P. L.
Published: November 2022

Aneuploidy is a hallmark of cancer and a major cause of miscarriages in humans. It is caused by chromosome segregation errors during cell divisions. Evidence is mounting that the probability of specific chromosomes undergoing a segregation error is non-random. In other words, some chromosomes have a higher chance of contributing to aneuploid karyotypes than others. This could have important implications for the origins of recurrent aneuploidy patterns in cancer and developing embryos. Here, we review recent progress in understanding the prevalence and causes of non-random chromosome segregation errors in mammalian mitosis and meiosis. We evaluate its potential impact on cancer and human reproduction and discuss possible research avenues.
Frontiers in Neurogenesis
Authors: Vaz Andreia , Ribeiro Inês , Pinto Luísa
Published: November 2022

One of the most intriguing dogmas in neurosciences—the empirical lack of brain neuronal regeneration in adulthood onwards to late life—began to be debunked initially by research groups focused on understanding postnatal (early days/weeks of murine and guinea pigs) neurodevelopmental and neuroplastic events [...]
Upregulation of YKL-40 Promotes Metastatic Phenotype and Correlates with Poor Prognosis and Therapy Response in Patients with Colorectal Cancer
Authors: De Robertis Mariangela , Greco Maria Raffaella , Cardone Rosa Angela , Mazza Tommaso , Marzano Flaviana , Mehterov Nikolay , Kazakova Maria , Belev Nikolay , Tullo Apollonia , Pesole Graziano , Sarafian Victoria , Signori Emanuela
Published: November 2022

YKL-40 is a heparin- and chitin-binding glycoprotein that belongs to the family of glycosyl hydrolases but lacks enzymatic properties. It affects different (patho)physiological processes, including cancer. In different tumors, YKL-40 gene overexpression has been linked to higher cell proliferation, angiogenesis, and vasculogenic mimicry, migration, and invasion. Because, in colorectal cancer (CRC), the serological YKL-40 level may serve as a risk predictor and prognostic biomarker, we investigated the underlying mechanisms by which it may contribute to tumor progression and the clinical significance of its tissue expression in metastatic CRC. We demonstrated that high-YKL-40-expressing HCT116 and Caco2 cells showed increased motility, invasion, and proliferation. YKL-40 upregulation was associated with EMT signaling activation. In the AOM/DSS mouse model, as well as in tumors and sera from CRC patients, elevated YKL-40 levels correlated with high-grade tumors. In retrospective analyses of six independent cohorts of CRC patients, elevated YKL-40 expression correlated with shorter survival in patients with advanced CRC. Strikingly, high YKL-40 tissue levels showed a predictive value for a better response to cetuximab, even in patients with stage IV CRC and mutant KRAS, and worse sensitivity to oxaliplatin. Taken together, our findings establish that tissue YKL-40 overexpression enhances CRC metastatic potential, highlighting this gene as a novel prognostic candidate, a predictive biomarker for therapy response, and an attractive target for future therapy in CRC.
Circular RNA hsa_circ_0051040 Promotes Hepatocellular Carcinoma Progression by Sponging miR-569 and Regulating ITGAV Expression
Authors: Ju Linling , Yao Min , Lu Rujian , Cao Yali , Wang Huixuan , Yuan Liuxia , Xiao Feng , Shao Jianguo , Cai Weihua , Chen Lin , Bian Zhaolian
Published: November 2022

Accumulating evidence has demonstrated the roles of circular RNAs (circRNAs) in hepatocellular carcinoma (HCC); however, their roles in HCC need to be further studied. Through high-throughput human circRNA microarray analysis of HCC and adjacent normal tissues, we identified hsa_circ_0051040 as a novel candidate circRNA for the diagnosis and treatment of HCC. In this study, we found that hsa_circ_0051040 was overexpressed in HCC tissues and cell lines and that its expression was correlated with poor prognosis. Knockdown of hsa_circ_0051040 inhibited the migration, invasion, and proliferation of HCC cells in vitro and in vivo, whereas overexpression of hsa_circ_0051040 had the opposite effects. Moreover, our data demonstrated that hsa_circ_0051040 acted as a sponge for miR-569 to regulate ITGAV expression and induce EMT progression. Our findings indicated that hsa_circ_0051040 promotes HCC development and progression by sponging miR-569 to increase ITGAV expression. Thus, hsa_circ_0051040 is a good candidate as a therapeutic target.
Identification and Analysis of Small Molecule Inhibitors of CRISPR-Cas9 in Human Cells
Authors: Yang Yue , Li Donghua , Wan Fen , Chen Bohong , Wu Guanglan , Li Feng , Ren Yanliang , Liang Puping , Wan Jian , Songyang Zhou
Published: November 2022

Genome editing tools based on CRISPR–Cas systems can repair genetic mutations in situ; however, off-target effects and DNA damage lesions that result from genome editing remain major roadblocks to its full clinical implementation. Protein and chemical inhibitors of CRISPR–Cas systems may reduce off-target effects and DNA damage. Here we describe the identification of several lead chemical inhibitors that could specifically inhibit the activity of Streptococcus pyogenes Cas9 (SpCas9). In addition, we obtained derivatives of lead inhibitors that could penetrate the cell membrane and inhibit SpCas9 in cellulo. Two of these compounds, SP2 and SP24, were able to improve the specificity of SpCas9 in cellulo at low-micromolar concentration. Furthermore, microscale thermophoresis (MST) assays showed that SP24 might inhibit SpCas9 activity by interacting with both the SpCas9 protein and the SpCas9–gRNA ribonucleoprotein complex. Taken together, SP24 is a novel chemical inhibitor of SpCas9 which has the potential to enhance therapies that utilize SpCas9.
A Concise Review on Dysregulation of LINC00665 in Cancers
Authors: Ghafouri-Fard Soudeh , Khoshbakht Tayyebeh , Hussen Bashdar Mahmud , Baniahmad Aria , Taheri Mohammad , Hajiesmaeili Mohammadreza
Published: November 2022

Long Intergenic Non-Protein Coding RNA 665 (LINC00665) is an RNA gene located on the minus strand of chromosome 19. This lncRNA acts as a competing endogenous RNA for miR-4458, miR-379-5p, miR-551b-5p, miR-3619-5p, miR-424-5p, miR-9-5p, miR-214-3p, miR-126-5p, miR-149-3p, miR-379-5p, miR-665, miR-34a-5p, miR-186-5p, miR-138-5p, miR-181c-5p, miR-98, miR-195-5p, miR-224-5p, miR-3619, miR-708, miR-101, miR-1224-5p, miR-34a-5p, and miR-142-5p. Via influencing expression of these miRNAs, it can enhance expression of a number of oncogenes. Moreover, LINC00665 can influence activity of Wnt/β-Catenin, TGF-β, MAPK1, NF-κB, ERK, and PI3K/AKT signaling. Function of this lncRNA has been assessed through gain-of-function tests and/or loss-of-function studies. Furthermore, diverse research groups have evaluated its expression levels in tissue samples using microarray and RT-qPCR techniques. In this manuscript, we have summarized the results of these studies and categorized them in three sections, i.e., cell line studies, animal studies, and investigations in clinical samples.
Targeting Wnt/β-Catenin Signaling Exacerbates Ferroptosis and Increases the Efficacy of Melanoma Immunotherapy via the Regulation of MITF
Authors: Wang Hao , Zhang Hengxiang , Chen Yuhan , Wang Huina , Tian Yangzi , Yi Xiuli , Shi Qiong , Zhao Tao , Zhang Baolu , Gao Tianwen , Guo Sen , Li Chunying , Guo Weinan
Published: November 2022

Melanoma is the most lethal form of skin cancer, resulting from the malignant transformation of epidermal melanocytes. Recent revolutionary progress in targeted therapy and immunotherapy has prominently improved the treatment outcome, but the survival of melanoma patients remains suboptimal. Ferroptosis is greatly involved in cancer pathogenesis and can execute the outcome of immunotherapy. However, the detailed regulatory mechanisms of melanoma cell ferroptosis remain elusive. Herein, we report that Wnt/β-catenin signaling regulates ferroptosis and melanoma immunotherapy efficacy via the regulation of MITF. First of all, we found that Wnt/β-catenin signaling was prominently suppressed in melanoma cell ferroptosis. Then, we proved that targeting β-catenin exacerbated melanoma cell ferroptosis by promoting the generation of lipid peroxidation both in vitro and in vivo. Subsequent mechanistic studies revealed that MITF mediated the effect of Wnt/β-catenin signaling on melanoma cell ferroptosis, and PGC1α and SCD1 were documented as two main effectors downstream of Wnt/β-catenin-MITF pathway. Ultimately, pharmacological inhibition of β-catenin or MITF increased the efficacy of anti-PD-1 immunotherapy in preclinical xenograft tumor model by promoting ferroptosis. Taken together, Wnt/β-catenin signaling deficiency exacerbates ferroptosis in melanoma via the regulation of MITF. Targeting Wnt/β-catenin-MITF pathway could be a promising strategy to potentiate ferroptosis and increase the efficacy of anti-PD-1 immunotherapy.
A Possible Modulator of Vitiligo Metabolic Impairment: Rethinking a PPARγ Agonist
Authors: Papaccio Federica , Bellei Barbara , Ottaviani Monica , D’Arino Andrea , Truglio Mauro , Caputo Silvia , Cigliana Giovanni , Sciuto Lorenzo , Migliano Emilia , Pacifico Alessia , Iacovelli Paolo , Picardo Mauro
Published: November 2022

Vitiligo is a complex disease wherein derangements in multiple pathways determine the loss of functional melanocytes. Since its pathogenesis is not yet completely understood, vitiligo lacks a definitive safe and efficacious treatment. At present, different therapies are available; however, each modality has its baggage of disadvantages and side effects. Recently we have described several metabolic abnormalities in cells from pigmented skin of vitiligo patients, including alterations of glucose metabolism. Therefore, we conducted a study to evaluate the effect of Pioglitazone (PGZ), a Peroxisome proliferator-activated receptor-γ (PPARγ) agonist, on cells from pigmented vitiligo skin. We treated vitiligo melanocytes and fibroblasts with low doses of PGZ and evaluated the effects on mitochondrial alterations, previously reported by our and other groups. Treatment with PGZ significantly increased mRNA and protein levels of several anaerobic glycolytic enzymes, without increasing glucose consumption. The PGZ administration fully restored the metabolic network, replacing mitochondrial membrane potential and mitochondrial DNA (mtDNA) copy number. These effects, together with a significant increase in ATP content and a decrease in reactive oxygen species (ROS) production, provide strong evidence of an overall improvement of mitochondria bioenergetics in vitiligo cells. Moreover, the expression of HMGB1, Hsp70, defined as a part of DAMPs, and PD-L1 were significantly reduced. In addition, PGZ likely reverts premature senescence phenotype. In summary, the results outline a novel mode of action of Pioglitazone, which may turn out to be relevant to the development of effective new vitiligo therapeutic strategies.
Integrin Conformational Dynamics and Mechanotransduction
Authors: Kolasangiani Reza , Bidone Tamara C. , Schwartz Martin A.
Published: November 2022

The function of the integrin family of receptors as central mediators of cell-extracellular matrix (ECM) and cell–cell adhesion requires a remarkable convergence of interactions and influences. Integrins must be anchored to the cytoskeleton and bound to extracellular ligands in order to provide firm adhesion, with force transmission across this linkage conferring tissue integrity. Integrin affinity to ligands is highly regulated by cell signaling pathways, altering affinity constants by 1000-fold or more, via a series of long-range conformational transitions. In this review, we first summarize basic, well-known features of integrin conformational states and then focus on new information concerning the impact of mechanical forces on these states and interstate transitions. We also discuss how these effects may impact mechansensitive cell functions and identify unanswered questions for future studies.