bluuebunny/crossref_metadata_2025 huggingface dataset:
Biomechanical Comparison of Salvage Pedicle Screw Augmentations Using Different Biomaterials
Authors: Li Yun-Da , Hsieh Ming-Kai , Lee De-Mei , Lin Yi-Jiun , Tsai Tsung-Ting , Lai Po-Liang , Tai Ching-Lung
Published: August 2022

Allograft bone particles, hydroxyapatite/β-hydroxyapatite-tricalcium phosphate (HA/β-TCP), calcium sulfate (CS), and polymethylmethacrylate (PMMA) bone cement are biomaterials clinically used to fill defective pedicles for pedicle screw augmentation. Few studies have systematically investigated the effects of various biomaterials utilized for salvage screw stabilization. The aim of this study was to evaluate the biomechanical properties of screws augmented with these four different materials and the effect of different pilot hole sizes and bone densities on screw fixation strength. Commercially available synthetic bones with three different densities (7.5 pcf, 15pcf, 30 pcf) simulating different degrees of bone density were utilized as substitutes for human bone. Two different pilot hole sizes (3.2 mm and 7.0 mm in diameter) were prepared on test blocks to simulate primary and revision pedicle screw fixation, respectively. Following separate specimen preparation with these four different filling biomaterials, a screw pullout test was conducted using a material test machine, and the average maximal screw pullout strength was compared among groups. The average maximal pullout strength of the materials, presented in descending order, was as follows: bone cement, calcium sulfate, HA/β-TCP, allograft bone chips and the control. In samples in both the 3.2 mm pilot-hole and 7.0 mm pilot-hole groups, the average maximal pullout strength of these four materials increased with increasing bone density. The average maximal pullout strength of the bone cement augmented salvage screw (7.0 mm) was apparently elevated in the 7.5 pcf test block. Salvage pedicle screw augmentation with allograft bone chips, HA/β-TCP, calcium sulfate, and bone cement are all feasible methods and can offer better pullout strength than materials in the non-augmentation group. Bone cement provides the most significantly augmented effect in each pilot hole size and bone density setting and could be considered preferentially to achieve larger initial stability during revision surgery, especially for bones with osteoporotic quality.
Influence of 30–60 Days Intraseasonal Oscillation of East Asian Summer Monsoon on Precipitation in Southwest China
Authors: Wang Yingsi , Xiao Tiangui , Dong Xuefeng , Li Yueqing , Huang Wei , Tan Jie
Published: August 2022

The intraseasonal oscillation (ISO) of the East Asian summer monsoon (EASM) is an important factor affecting summer precipitation in China, but the relationship between the ISO of the EASM and summer precipitation in southwest China is currently still unclear. The relationship between the two is discussed, and the following conclusions are drawn: (1) there is a significant positive correlation between East Asian monsoon surge intensity and summer precipitation in southwest China. When the monsoon surge is stronger (weaker), the precipitation in southwest China is more (less). However, the areas where the monsoon surge has a more obvious effect on the summer precipitation in southwest China are mainly located east of 105° E, and the monsoon surge has no obvious effect on the area west of 105° E. This may be more (less) the case in monsoon surge years, when a low-frequency oscillation of 30–60 days (10–20 days) plays a dominant role. The East Asian region has a longitudinal wave train of “+ − +” (“− + −“), the western Pacific subtropical high is westerly (easterly), the South China Sea and western Pacific is affected by anticyclone (cyclone), the EASM is active (suppressive), eastern southwest China has water vapor convergence (divergence) and upward (downward) airflow. (2) We found that 1998 was a typical year for the 30–60 days ISO of the EASM. There are two obvious 30–60 days oscillation cycles. In this year, when the intensity of the ISO of the EASM increases (decreases), the range of positive precipitation anomaly region in southwest China extends (decreases). The atmospheric circulation characteristics show that, when the western Pacific subtropical high is west (east) and south (north), and there is obvious anticyclonic (cyclonic) circulation in China–western Pacific, and the EASM is stronger (weaker), which leads to more (less) precipitation in southwest China.
Investigation of a Gaussian Plume in the Vicinity of an Urban Cyclotron Using Helium as a Tracer Gas
Authors: Laguionie Philippe , Connan Olivier , Tien Thinh Lai , Vecchiola Sophie , Chardeur Johann , Cazimajou Olivier , Solier Luc , Charvolin-Volta Perrine , Chen Liying , Korsakissok Irène , Guellec Malo Le , Soulhac Lionel , Tripathi Amita , Maro Denis
Published: August 2022

Studies focusing on the radiological impact of fluorine 18 on populations living near to cyclotrons (<200 m) frequently assume normal distribution of atmospheric concentration for simplification purposes. On this basis, Gaussian models are used, despite their limits, as deployment requires little input data and computing resources. To estimate the ability of a Gaussian model to predict atmospheric dispersion in an urban environment, we used helium as a new passive tracer of atmospheric dispersion in the near-field range (<500 m) of the Beuvry hospital cyclotron (France). The atmospheric transfer coefficients measured in the field were compared with those modeled using a Gaussian equation. According to the results, helium is an effective tracer of atmospheric dispersion when attempting to determine atmospheric transfer coefficients ( downwind of a discharge point. The Briggs-rural, Briggs-urban and Doury Gaussian models underestimate and sometimes maximum in the prevailing weather conditions during the experiments. By compiling the results of this study with data from the literature, it appears that the maximum observed obey a power law as a function of the distance from the discharge point, for distances from the discharge point in excess of 20 m.
Chemical Scalpel: An Experimental Collagenase-Based Treatment for Peritoneal Adhesions
Authors: Barambio Javier , García-Arranz Mariano , Villarejo Campos Pedro Villarejo , Vélez Pinto Juan Felipe Vélez , Clemente Luz Vega , Gómez-Heras Soledad García , Guadalajara Héctor , García-Olmo Damián
Published: August 2022

(1) Background: Abdominal adhesions are a common disease appearing after any type of abdominal surgery and may prolong surgical time and cause intestinal obstruction, infertility, or chronic pain. We propose the use of intraperitoneal collagenase to perform chemical adhesiolysis based on the pathophysiology and histology of adhesions. (2) Methods: We generated an adhesion model with intraperitoneal polypropylene meshes. Four months later, we evaluated the efficacy of the treatment in blinded form, i.e., 0.05% collagenase vs. placebo at 37 °C for 20 min. Protocol 1: Ten rats with ten mesh fragments, in which an attempt was made to remove the maximum number of meshes in a 5-min period. Protocol 2: Six rats with four mesh fragments in the sides of the abdominal cavity in which adhesiolysis was performed using a device that measures burst pressure. (3) Results: Protocol 1: 42% efficacy in the collagenase group versus 8% in the control group (p < 0.013). Protocol 2: 188.25 mmHg (SD 69.65) in the collagenase group vs. 325.76 mmHg (SD 50.25) in the control group (p < 0.001). (4) Conclusions: Collagenase allows for the safe and effective chemical adhesiolysis in this experimental model of adhesions.
Crocodile Oil Disrupts Mitochondrial Homeostasis and Exacerbates Diabetic Kidney Injury in Spontaneously Diabetic Torii Rats
Authors: Wai Linn Thiri , Kobroob Anongporn , Ngernjan Metas , Amornlerdpison Doungporn , Lailerd Narissara , Wongmekiat Orawan
Published: August 2022

Diabetic nephropathy is currently the leading cause of end-stage renal disease (ESRD) in type 2 diabetes. Studies have suggested that supplementation with some fatty acids might reduce the risk and delay the progression to ESRD in patient with chronic kidney disease. Crocodile oil (CO) contains a variety of fatty acids, especially omega-3, -6 and -9, that have been reported to be beneficial to human health. This study examined the impact of long-term CO supplementation on the development of diabetic nephropathy in spontaneously diabetic Torii (SDT) rats. After diabetic verification, SDT rats were assigned to receive vehicle or CO at 500 and 1000 mg/kg BW, respectively, by oral gavage. Age-matched nondiabetic Sprague–Dawley rats were given vehicle or high-dose CO. After 28 weeks of intervention, CO failed to improve hyperglycemia and pancreatic histopathological changes in SDT rats. Unexpectedly, CO dose-dependently exacerbated the impairment of kidney and mitochondrial functions caused by diabetes. CO also disturbed the expressions of proteins involved in mitochondrial biogenesis, dynamics, and mitophagy. However, no significant alterations were observed in nondiabetic rats receiving high-dose CO. The findings reveal that CO has deleterious effects that aggravate diabetic kidney injury via disrupting mitochondrial homeostasis, possibly due to its improper omega-6: omega-3 ratio.
Isolation, Characterization, and Autophagy Function of BECN1-Splicing Isoforms in Cancer Cells
Authors: Maheshwari Chinmay , Vidoni Chiara , Titone Rossella , Castiglioni Andrea , Lora Claudia , Follo Carlo , Isidoro Ciro
Published: August 2022

Alternative splicing allows the synthesis of different protein variants starting from a single gene. Human Beclin 1 (BECN1) is a key autophagy regulator that acts as haploinsufficient tumor suppressor since its decreased expression correlates with tumorigenesis and poor prognosis in cancer patients. Recent studies show that BECN1 mRNA undergoes alternative splicing. Here, we report on the isolation and molecular and functional characterization of three BECN1 transcript variants (named BECN1-α, -β and -γ) in human cancer cells. In ovarian cancer NIHOVCAR3, these splicing variants were found along with the canonical wild-type. BECN1-α lacks 143 nucleotides at its C-terminus and corresponds to a variant previously described. BECN1-β and -γ lack the BCL2 homology 3 domain and other regions at their C-termini. Following overexpression in breast cancer cells MDA-MB231, we found that BECN1-α stimulates autophagy. Specifically, BECN1-α binds to Parkin and stimulates mitophagy. On the contrary, BECN1-β reduces autophagy with a dominant negative effect over the endogenous wild-type isoform. BECN1-γ maintains its ability to interact with the vacuolar protein sorting 34 and only has a slight effect on autophagy. It is possible that cancer cells utilize the alternative splicing of BECN1 for modulating autophagy and mitophagy in response to environmental stresses.
Let-7 as a Promising Target in Aging and Aging-Related Diseases: A Promise or a Pledge
Authors: Wang Ya , Zhao Juanjuan , Chen Shipeng , Li Dongmei , Yang Jing , Zhao Xu , Qin Ming , Guo Mengmeng , Chen Chao , He Zhixu , Zhou Ya , Xu Lin
Published: August 2022

The abnormal regulation and expression of microRNA (miRNA) are closely related to the aging process and the occurrence and development of aging-related diseases. Lethal-7 (let-7) was discovered in Caenorhabditis elegans (C. elegans) and plays an important role in development by regulating cell fate regulators. Accumulating evidence has shown that let-7 is elevated in aging tissues and participates in multiple pathways that regulate the aging process, including affecting tissue stem cell function, body metabolism, and various aging-related diseases (ARDs). Moreover, recent studies have found that let-7 plays an important role in the senescence of B cells, suggesting that let-7 may also participate in the aging process by regulating immune function. Therefore, these studies show the diversity and complexity of let-7 expression and regulatory functions during aging. In this review, we provide a detailed overview of let-7 expression regulation as well as its role in different tissue aging and aging-related diseases, which may provide new ideas for enriching the complex expression regulation mechanism and pathobiological function of let-7 in aging and related diseases and ultimately provide help for the development of new therapeutic strategies.
Predictive Value of HbA1c and Metabolic Syndrome for Renal Outcome in Non-Diabetic CKD Stage 1–4 Patients
Authors: Hung Chi-Chih , Zhen Yen-Yi , Niu Sheng-Wen , Lin Kun-Der , Lin Hugo You-Hsien , Lee Jia-Jung , Chang Jer-Ming , Kuo I-Ching
Published: August 2022

Glycated hemoglobin (HbA1c) levels are commonly used to indicate long-term glycemic control. An HbA1c level of 6.5–5.7% is defined as pre-diabetes and is proposed as a criterion for diagnosing metabolic syndrome (MetS). However, HbA1c levels can be affected by chronic kidney disease (CKD). Whether HbA1c is associated with clinical outcomes in nondiabetic CKD patients with or without MetS is still unknown. This study included 1270 nondiabetic CKD stage 1–4 Asian patients, divided by HbA1c and MetS. Through linear regression, HbA1c was positively associated with age, waist circumference, hemoglobin levels, and C-reactive protein and was negatively associated with malnutrition–inflammation. HbA1c levels were 5.5% (0.6%) and 5.7% (0.6%) in non-MetS and MetS, respectively (p < 0.001). In Cox regression, higher-level HbA1c was associated with worse composite renal outcome in MetS patients, but with better renal outcome in non-MetS patients: Hazard ratio (HR) (95% confidence interval [CI]) of HbA1c ≥5.7%, compared with HbA1c <5%, was 2.00 (1.06–3.78) in MetS and 0.25 (0.14–0.45) in non-MetS. An association between HbA1c and all-cause mortality was not found. In conclusion, higher HbA1c levels are associated with worse renal outcomes in nondiabetic CKD stage 1–4 patients modified by the presence of MetS.
Post-Synapses in the Brain: Role of Dendritic and Spine Structures
Authors: Meldolesi Jacopo
Published: August 2022

Brain synapses are neuronal structures of the greatest interest. For a long time, however, the knowledge about them was variable, and interest was mostly focused on their pre-synaptic portions, especially neurotransmitter release from axon terminals. In the present review interest is focused on post-synapses, the structures receiving and converting pre-synaptic messages. Upon further modulation, such messages are transferred to dendritic fibers. Dendrites are profoundly different from axons; they are shorter and of variable thickness. Their post-synapses are of two types. Those called flat/intended/aspines, integrated into dendritic fibers, are very frequent in inhibitory neurons. The spines, small and stemming protrusions, connected to dendritic fibers by their necks, are present in almost all excitatory neurons. Several structures and functions including the post-synaptic densities and associated proteins, the nanoscale mechanisms of compartmentalization, the cytoskeletons of actin and microtubules, are analogous in the two post-synaptic forms. However other properties, such as plasticity and its functions of learning and memory, are largely distinct. Several properties of spines, including emersion from dendritic fibers, growth, change in shape and decreases in size up to disappearance, are specific. Spinal heads correspond to largely independent signaling compartments. They are motile, their local signaling is fast, however transport through their thin necks is slow. When single spines are activated separately, their dendritic effects are often lacking; when multiple spines are activated concomitantly, their effects take place. Defects of post-synaptic responses, especially those of spines, take place in various brain diseases. Here alterations affecting symptoms and future therapy are shown to occur in neurodegenerative diseases and autism spectrum disorders.
Effect of Lauric vs. Oleic Acid-Enriched Diets on Leptin Autoparacrine Signalling in Male Mice
Authors: Fernández-Felipe Jesús , Plaza Adrián , Domínguez Gema , Pérez-Castells Javier , Cano Victoria , Cioni Francesco , Del Olmo Nuria , Ruiz-Gayo Mariano , Merino Beatriz
Published: August 2022

High-fat diets enriched with lauric acid (SOLF) do not enhance leptin production despite expanding white adipose tissue (WAT). Our study aimed at identifying the influence of SOLF vs. oleic acid-enriched diets (UOLF) on the autoparacrine effect of leptin and was carried out on eight-week-old mice consuming control chow, UOLF or SOLF. Phosphorylation of kinases integral to leptin receptor (LepR) signalling pathways (705Tyr-STAT3, 473Ser-Akt, 172Thr-AMPK), adipocyte-size distribution, fatty acid content, and gene expression were analyzed in WAT. SOLF enhanced basal levels of phosphorylated proteins but reduced the ability of leptin to enhance kinase phosphorylation. In contrast, UOLF failed to increase basal levels of phosphorylated proteins and did not modify the effect of leptin. Both SOLF and UOLF similarly affected adipocyte-size distribution, and the expression of genes related with adipogenesis and inflammation. WAT composition was different between groups, with SOLF samples mostly containing palmitic, myristic and lauric acids (>48% w/w) and UOLF WAT containing more than 80% (w/w) of oleic acid. In conclusion, SOLF appears to be more detrimental than UOLF to the autoparacrine leptin actions, which may have an impact on WAT inflammation. The effect of SOLF and UOLF on WAT composition may affect WAT biophysical properties, which are able to condition LepR signaling.
Internal Ribosome Entry Site (IRES)-Mediated Translation and Its Potential for Novel mRNA-Based Therapy Development
Authors: Marques Rita , Lacerda Rafaela , Romão Luísa
Published: August 2022

Many conditions can benefit from RNA-based therapies, namely, those targeting internal ribosome entry sites (IRESs) and their regulatory proteins, the IRES trans-acting factors (ITAFs). IRES-mediated translation is an alternative mechanism of translation initiation, known for maintaining protein synthesis when canonical translation is impaired. During a stress response, it contributes to cell reprogramming and adaptation to the new environment. The relationship between IRESs and ITAFs with tumorigenesis and resistance to therapy has been studied in recent years, proposing new therapeutic targets and treatments. In addition, IRES-dependent translation initiation dysregulation is also related to neurological and cardiovascular diseases, muscular atrophies, or other syndromes. The participation of these structures in the development of such pathologies has been studied, yet to a far lesser extent than in cancer. Strategies involving the disruption of IRES–ITAF interactions or the modification of ITAF expression levels may be used with great impact in the development of new therapeutics. In this review, we aim to comprehend the current data on groups of human pathologies associated with IRES and/or ITAF dysregulation and their application in the designing of new therapeutic approaches using them as targets or tools. Thus, we wish to summarise the evidence in the field hoping to open new promising lines of investigation toward personalised treatments.
Stabilization of F-Actin Cytoskeleton by Paclitaxel Improves the Blastocyst Developmental Competence through P38 MAPK Activity in Porcine Embryos
Authors: Joe Seung-Yeon , Yang Seul-Gi , Lee Jae-Ho , Park Hyo-Jin , Koo Deog-Bon
Published: August 2022

Changes in F-actin distribution and cortical F-actin morphology are important for blastocyst developmental competence during embryogenesis. However, the effect of paclitaxel as a microtubule stabilizer on embryonic development in pigs remains unclear. We investigated the role of F-actin cytoskeleton stabilization via P38 MAPK activation using paclitaxel to improve the developmental potential of blastocysts in pigs. In this study, F-actin enrichment and adducin expression based on blastomere fragment rate and cytokinesis defects were investigated in cleaved embryos after in vitro fertilization (IVF). Adducin and adhesive junction F-actin fluorescence intensity were significantly reduced with increasing blastomere fragment rate in porcine embryos. In addition, porcine embryos were cultured with 10 and 100 nM paclitaxel for two days after IVF. Adhesive junction F-actin stabilization and p-P38 MAPK activity in embryos exposed to 10 nM paclitaxel increased significantly with blastocyst development competence. However, increased F-actin aggregation, cytokinesis defects, and over-expression of p-P38 MAPK protein by 100 nM paclitaxel exposure disrupted blastocyst development in porcine embryos. In addition, exposure to 100 nM paclitaxel increased the misaligned α-tubulin of spindle assembly and adhesive junction F-actin aggregation at the blastocyst stage, which might be caused by p-P38 protein over-expression-derived apoptosis in porcine embryos.
A Machine Learning Framework for Detecting COVID-19 Infection Using Surface-Enhanced Raman Scattering
Authors: Ikponmwoba Eloghosa , Ukorigho Okezzi , Moitra Parikshit , Pan Dipanjan , Gartia Manas Ranjan , Owoyele Opeoluwa
Published: August 2022

In this study, we explored machine learning approaches for predictive diagnosis using surface-enhanced Raman scattering (SERS), applied to the detection of COVID-19 infection in biological samples. To do this, we utilized SERS data collected from 20 patients at the University of Maryland Baltimore School of Medicine. As a preprocessing step, the positive-negative labels are obtained using Polymerase Chain Reaction (PCR) testing. First, we compared the performance of linear and nonlinear dimensionality techniques for projecting the high-dimensional Raman spectra to a low-dimensional space where a smaller number of variables defines each sample. The appropriate number of reduced features used was obtained by comparing the mean accuracy from a 10-fold cross-validation. Finally, we employed Gaussian process (GP) classification, a probabilistic machine learning approach, to correctly predict the occurrence of a negative or positive sample as a function of the low-dimensional space variables. As opposed to providing rigid class labels, the GP classifier provides a probability (ranging from zero to one) that a given sample is positive or negative. In practice, the proposed framework can be used to provide high-throughput rapid testing, and a follow-up PCR can be used for confirmation in cases where the model’s uncertainty is unacceptably high.
Intraoperative Cerebral Hemodynamic Monitoring during Carotid Endarterectomy via Diffuse Correlation Spectroscopy and Near-Infrared Spectroscopy
Authors: Kaya Kutlu , Zavriyev Alexander I. , Orihuela-Espina Felipe , Simon Mirela V. , LaMuraglia Glenn M. , Pierce Eric T. , Franceschini Maria Angela , Sunwoo John
Published: August 2022

Objective: This pilot study aims to show the feasibility of noninvasive and real-time cerebral hemodynamic monitoring during carotid endarterectomy (CEA) via diffuse correlation spectroscopy (DCS) and near-infrared spectroscopy (NIRS). Methods: Cerebral blood flow index (CBFi) was measured unilaterally in seven patients and bilaterally in seventeen patients via DCS. In fourteen patients, hemoglobin oxygenation changes were measured bilaterally and simultaneously via NIRS. Cerebral autoregulation (CAR) and cerebrovascular resistance (CVR) were estimated using CBFi and arterial blood pressure data. Further, compensatory responses to the ipsilateral hemisphere were investigated at different contralateral stenosis levels. Results: Clamping of carotid arteries caused a sharp increase of CVR (~70%) and a marked decrease of ipsilateral CBFi (57%). From the initial drop, we observed partial recovery in CBFi, an increase of blood volume, and a reduction in CVR in the ipsilateral hemisphere. There were no significant changes in compensatory responses between different contralateral stenosis levels as CAR was intact in both hemispheres throughout the CEA phase. A comparison between hemispheric CBFi showed lower ipsilateral levels during the CEA and post-CEA phases (p < 0.001, 0.03). Conclusion: DCS alone or combined with NIRS is a useful monitoring technique for real-time assessment of cerebral hemodynamic changes and allows individualized strategies to improve cerebral perfusion during CEA by identifying different hemodynamic metrics.
Actin Retrograde Flow Regulated by the Wiskott–Aldrich Syndrome Protein Drives the Natural Killer Cell Response
Authors: Sabag Batel , Levy Moria , Kivelevitz Jessica , Dashevsky Nataly , Ben-Shmuel Aviad , Puthenveetil Abhishek , Awwad Fatima , Barda-Saad Mira
Published: August 2022

Understanding the crosstalk between natural killer (NK) cells and the tumor microenvironment (TME) has enhanced the potential of exploiting the interplay between activation and inhibition of NK cells for immunotherapy. This interaction is crucial for understanding how tumor cells escape NK cell immune surveillance. NK cell dysfunction is regulated by two molecular mechanisms, downregulated activating receptor ligand expression on the tumor cells, and upregulated inhibitory signals delivered to NK cells. Recent studies demonstrated the role of mechanotransduction in modulating NK cell responses in the TME. The immunological synapse represents a functional interface between the NK cell and its target, regulated by Actin Retrograde Flow (ARF), which drives the adhesion molecules and receptors toward the central zone of the immunological synapse (IS). Here, we further characterize the role of ARF in controlling the immune response of NK cells, using CRISPR/cas9-mediated Wiskott–Aldrich Syndrome protein (WASp) gene silencing of NK cells. We demonstrate that WASp regulates ARF velocity, affecting the conformation and function of the key NK inhibitory regulator, SH2-domain containing protein tyrosine phosphatase-1 (SHP-1), and consequently, the NK cell response. Our results demonstrate the potential of modulating the biophysical and intracellular regulation of NK activation as a promising approach for improving immunotherapy.
Organoids as a Model for Precision Medicine in Malignant Pleural Mesothelioma: Where Are We Today?
Authors: Gao Yanyun , Kruithof-de Julio Marianna , Peng Ren-Wang , Dorn Patrick
Published: August 2022

MPM is an aggressive tumor originating from pleural mesothelial cells. A characteristic feature of the disease is the dominant prevalence of therapeutically intractable inactivating alterations in TSGs, making MPM one of the most difficult cancers to treat and the epitome of a cancer characterized by a significant lack of therapy options and an extremely poor prognosis (5-year survival rate of only 5% to 10%). Extensive interpatient heterogeneity poses another major challenge for targeted therapy of MPM, warranting stratified therapy for specific subgroups of MPM patients. Accurate preclinical models are critical for the discovery of new therapies and the development of personalized medicine. Organoids, an in vitro ‘organ-like’ 3D structure derived from patient tumor tissue that faithfully mimics the biology and complex architecture of cancer and largely overcomes the limitations of other existing models, are the next-generation tumor model. Although organoids have been successfully produced and used in many cancers, the development of MPM organoids is still in its infancy. Here, we provide an overview of recent advances in cancer organoids, focusing on the progress and challenges in MPM organoid development. We also elaborate the potential of MPM organoids for understanding MPM pathobiology, discovering new therapeutic targets, and developing personalized treatments for MPM patients.
Genome-Wide Identification and Validation of Gene Expression Biomarkers in the Diagnosis of Ovarian Serous Cystadenocarcinoma
Authors: Zalfa Francesca , Perrone Maria Grazia , Ferorelli Savina , Laera Luna , Pierri Ciro Leonardo , Tolomeo Anna , Dimiccoli Vincenzo , Perrone Giuseppe , De Grassi Anna , Scilimati Antonio
Published: August 2022

Ovarian cancer is the second most prevalent gynecologic malignancy, and ovarian serous cystadenocarcinoma (OSCA) is the most common and lethal subtype of ovarian cancer. Current screening methods have strong limits on early detection, and the majority of OSCA patients relapse. In this work, we developed and cross-validated a method for detecting gene expression biomarkers able to discriminate OSCA tissues from healthy ovarian tissues and other cancer types with high accuracy. A preliminary ranking-based approach was applied, resulting in a panel of 41 over-expressed genes in OSCA. The RNA quantity gene expression of the 41 selected genes was then cross-validated by using NanoString nCounter technology. Moreover, we showed that the RNA quantity of eight genes (ADGRG1, EPCAM, ESRP1, MAL2, MYH14, PRSS8, ST14 and WFDC2) discriminates each OSCA sample from each healthy sample in our data set with sensitivity of 100% and specificity of 100%. For the other three genes (MUC16, PAX8 and SOX17) in combination, their RNA quantity may distinguish OSCA from other 29 tumor types.
Clinical Applications of PSMA PET Examination in Patients with Prostate Cancer
Authors: Rasul Sazan , Haug Alexander R.
Published: August 2022

With the progressive aging of the population in industrially developed countries, as well as advances in diagnostic and biopsy techniques and improvements in patient awareness, the incidence of prostate cancer (PCa) is continuously increasing worldwide. Therefore, PCa is currently considered as the second leading cause of tumor-related death. Early detection of the tumor and its metastasis is essential, as the rate of disease recurrence is high and occurs in 27% to 53% of all patients who underwent curative therapy with radical prostatectomy or local radiotherapy. In this regard, the prostate specific membrane antigens, abbreviated as PSMAs, are type II membrane proteins that are highly expressed on the surface of malignant prostate tissue in PCa, particularly in aggressive, androgen-deprived, metastatic, and hormone-refractory PCa, and they are inversely associated with the androgen level. Up to 95% of adenocarcinomas of the prostate express PSMA receptors on their surface. Today, radionuclides that bind to these PSMA peptides are widely accepted for diagnostic and therapeutic purposes to specifically image and target prostate tumor cells at the molecular level, a process referred to as targeted theranostics. Numerous studies have demonstrated that the integration of these peptides into diagnostic and therapeutic procedures plays a critical role in the primary staging and treatment decisions of especially high-risk PCa, expands therapeutic options for patients with advanced stage of prostate tumor, and prolongs patients’ survival rate. In this review article, we intend to briefly spotlight the latest clinical utilization of the PSMA-targeted radioligand PET imaging modality in patients with different stages of PCa. Furthermore, limitations and pitfalls of this diagnostic technique are presented.
A Study on the Evaluation Methods of Nitrogen Oxide Removal Performance of Photocatalytic Concrete for Outdoor Applications
Authors: Park Hee-Ju , Hossain Sayed Mukit , Choi Kiin , Shon Ho-Kyong , Kim Jong-Ho
Published: August 2022

In Korea, the issue of particulate matter pollution is growing, and many solutions are being developed to deal with it. Photocatalytic technology has been found to be helpful in removing precursors such as nitrogen oxides that cause particulate matter. In a microcosm setup, ISO 22197-1 has been successfully used to quantify the removal of nitrogen oxides from the specimen to which the photocatalyst is applied. However, owing to a lack of suitable tools, on-site measurement of real-scale efficacy is difficult. Depending on the substrate and surrounding circumstances at the application location, the photocatalyst may function at varying levels. Additionally, the expected photocatalytic effect may differ depending on the ambient air quality and sunlight irradiation intensity. This article describes two approaches for studying outdoor concrete photocatalysis. Standard gas measurement and dual-reactor measurement are the recommended evaluation approaches. The standard gas measurement method was found useful for assessing the applied photocatalyst itself as an outcome of field assessment. The performance of photocatalysts at different sites was found to be mutually exclusive and comparable. Over 180 min, on a building roof deck, the NO removal by the standard gas method was 0.68 ppm, whereas, at two shaded locations, the removal amount was 0.51 ppm (side wall) and 0.24 ppm (underpass) for 300 min. The dual reactor measurement approach, on the other hand, was discovered to be one of the most suitable methods for assessing how much of an improvement there has been in the air quality in areas where photocatalysts have been placed.
The Effect of Y Zeolites with Different Pores on Tetralin Hydrocracking for the Production of High-Value Benzene, Toluene, Ethylbenzene and Xylene Products
Authors: Xian Ce , Mao Yichao , Long Xiangyun , Wu Ziming , Li Xiang , Cao Zhengkai
Published: August 2022

A series of Y zeolites with different pore properties was prepared as a support for hydrocracking catalysts for the production of BTEX (benzene, toluene, ethyl-benzene, and xylene) from tetralin. Some important characterizations, including N2 adsorption–desorption, NH3-TPD, Py-IR, and HRTEM, were applied to obtain the properties of different catalysts. Meanwhile, the tetralin hydrocracking performances of those catalysts were investigated on a high-pressure fixed-bed microreactor. The results showed that Si/Al ratio is the core property of zeolites and that the increase in the Vmicro/Vmeso of zeolites could facilitate the formation of BTEX products by hydrocracking tetralin. The method of hydrocracking tetralin was proposed. It was also found that the hydrogenation–cracking path was controlled by aromatic saturation thermodynamics, and strong acidity aided the backward shift of equilibrium temperature.
The Bacterial ClpXP-ClpB Family Is Enriched with RNA-Binding Protein Complexes
Authors: Auburger Georg , Key Jana , Gispert Suzana
Published: August 2022

In the matrix of bacteria/mitochondria/chloroplasts, Lon acts as the degradation machine for soluble proteins. In stress periods, however, proteostasis and survival depend on the strongly conserved Clp/Hsp100 family. Currently, the targets of ATP-powered unfoldases/disaggregases ClpB and ClpX and of peptidase ClpP heptameric rings are still unclear. Trapping experiments and proteome profiling in multiple organisms triggered confusion, so we analyzed the consistency of ClpP-trap targets in bacteria. We also provide meta-analyses of protein interactions in humans, to elucidate where Clp family members are enriched. Furthermore, meta-analyses of mouse complexomics are provided. Genotype–phenotype correlations confirmed our concept. Trapping, proteome, and complexome data retrieved consistent coaccumulation of CLPXP with GFM1 and TUFM orthologs. CLPX shows broad interaction selectivity encompassing mitochondrial translation elongation, RNA granules, and nucleoids. CLPB preferentially attaches to mitochondrial RNA granules and translation initiation components; CLPP is enriched with them all and associates with release/recycling factors. Mutations in CLPP cause Perrault syndrome, with phenotypes similar to defects in mtDNA/mtRNA. Thus, we propose that CLPB and CLPXP are crucial to counteract misfolded insoluble protein assemblies that contain nucleotides. This insight is relevant to improve ClpP-modulating drugs that block bacterial growth and for the treatment of human infertility, deafness, and neurodegeneration.
Fibrotic Scar in CNS Injuries: From the Cellular Origins of Fibroblasts to the Molecular Processes of Fibrotic Scar Formation
Authors: Ayazi Maryam , Zivkovic Sandra , Hammel Grace , Stefanovic Branko , Ren Yi
Published: August 2022

Central nervous system (CNS) trauma activates a persistent repair response that leads to fibrotic scar formation within the lesion. This scarring is similar to other organ fibrosis in many ways; however, the unique features of the CNS differentiate it from other organs. In this review, we discuss fibrotic scar formation in CNS trauma, including the cellular origins of fibroblasts, the mechanism of fibrotic scar formation following an injury, as well as the implication of the fibrotic scar in CNS tissue remodeling and regeneration. While discussing the shared features of CNS fibrotic scar and fibrosis outside the CNS, we highlight their differences and discuss therapeutic targets that may enhance regeneration in the CNS.
Single Cell Analysis Reveals Reciprocal Tumor-Macrophage Intercellular Communications Related with Metabolic Reprogramming in Stem-like Gastric Cancer
Authors: Sung Ji-Yong , Cheong Jae-Ho
Published: August 2022

Metabolic alterations and direct cell–cell interactions in the tumor microenvironment (TME) affect the prognostic molecular landscape of tumors; thus, it is imperative to investigate metabolic activity at the single-cell level rather than in bulk samples to understand the high-resolution mechanistic influences of cell-type specific metabolic pathway alterations on tumor cells. To investigate tumor metabolic reprogramming and intercellular communication at the single-cell level, we analyzed eighty-four metabolic pathways, seven metabolic signatures, and tumor-stroma cell interaction using 21,084 cells comprising gastric cancer and paired normal tissue. High EMT-score cells and stem-like subtype tumors showed elevated glycosaminoglycan metabolism, which was associated with poor patient outcome. Adenocarcinoma and macrophage cells had higher reactive oxidative species levels than the normal controls; they largely constituted the highest stemness cluster. They were found to reciprocally communicate through the common ligand RPS19. Consequently, ligand-target regulated transcriptional reprogramming resulted in HS6ST2 expression in adenocarcinoma cells and SERPINE1 expression in macrophages. Gastric cancer patients with increased SERPINE1 and HS6ST2 expression had unfavorable prognoses, suggesting these as potential drug targets. Our findings indicate that malignant stem-like/EMT cancer cell state might be regulated through reciprocal cancer cell-macrophage intercellular communication and metabolic reprogramming in the heterogeneous TME of gastric cancer at the single-cell level.
Therapeutic Targeting Notch2 Protects Bone Micro-Vasculatures from Methotrexate Chemotherapy-Induced Adverse Effects in Rats
Authors: Peymanfar Yaser , Su Yu-Wen , Hassanshahi Mohammadhossein , Xian Cory J.
Published: August 2022

Intensive cancer chemotherapy is well known to cause bone vasculature disfunction and damage, but the mechanism is poorly understood and there is a lack of treatment. Using a rat model of methotrexate (MTX) chemotherapy (five once-daily dosses at 0.75 mg/kg), this study investigated the roles of the Notch2 signalling pathway in MTX chemotherapy-induced bone micro-vasculature impairment. Gene expression, histological and micro-computed tomography (micro-CT) analyses revealed that MTX-induced micro-vasculature dilation and regression is associated with the induction of Notch2 activity in endothelial cells and increased production of inflammatory cytokine tumour necrosis factor alpha (TNFα) from osteoblasts (bone forming cells) and bone marrow cells. Blockade of Notch2 by a neutralising antibody ameliorated MTX adverse effects on bone micro-vasculature, both directly by supressing Notch2 signalling in endothelial cells and indirectly via reducing TNFα production. Furthermore, in vitro studies using rat bone marrow-derived endothelial cell revealed that MTX treatment induces Notch2/Hey1 pathway and negatively affects their ability in migration and tube formation, and Notch2 blockade can partially protect endothelial cell functions from MTX damage.
Serotonin Receptor 5-HT2A Regulates TrkB Receptor Function in Heteroreceptor Complexes
Authors: Ilchibaeva Tatiana , Tsybko Anton , Zeug Andre , Müller Franziska E. , Guseva Daria , Bischoff Stephan , Ponimaskin Evgeni , Naumenko Vladimir
Published: August 2022

Serotonin receptor 5-HT2A and tropomyosin receptor kinase B (TrkB) strongly contribute to neuroplasticity regulation and are implicated in numerous neuronal disorders. Here, we demonstrate a physical interaction between 5-HT2A and TrkB in vitro and in vivo using co-immunoprecipitation and biophysical and biochemical approaches. Heterodimerization decreased TrkB autophosphorylation, preventing its activation with agonist 7,8-DHF, even with low 5-HT2A receptor expression. A blockade of 5-HT2A receptor with the preferential antagonist ketanserin prevented the receptor-mediated downregulation of TrkB phosphorylation without restoring the TrkB response to its agonist 7,8-DHF in vitro. In adult mice, intraperitoneal ketanserin injection increased basal TrkB phosphorylation in the frontal cortex and hippocampus, which is in accordance with our findings demonstrating the prevalence of 5-HT2A–TrkB heteroreceptor complexes in these brain regions. An expression analysis revealed strong developmental regulation of 5-HT2A and TrkB expressions in the cortex, hippocampus, and especially the striatum, demonstrating that the balance between TrkB and 5-HT2A may shift in certain brain regions during postnatal development. Our data reveal the functional role of 5-HT2A–TrkB receptor heterodimerization and suggest that the regulated expression of 5-HT2A and TrkB is a molecular mechanism for the brain-region-specific modulation of TrkB functions during development and under pathophysiological conditions.
TP53INP2 Contributes to TGF-β2-Induced Autophagy during the Epithelial–Mesenchymal Transition in Posterior Capsular Opacification Development
Authors: Cui Yilei , Yang Hao , Shi Silu , Ping Xiyuan , Zheng Sifan , Tang Xiajing , Yu Xiaoning , Shentu Xingchao
Published: August 2022

Background: Posterior capsule opacification (PCO) is the most common complication after cataract surgery, in which increased levels of transforming growth factor-beta 2 (TGF-β2) accelerate PCO formation; however, the pathological mechanisms are not fully understood. This study aims to explore the regulation mechanism of TGF-β2 in PCO formation via its autophagic functions. Methods: The autophagic effect of TGF-β2 was detected by transmission electron microscopy (TEM), Western blotting, and immunofluorescence analysis. The association between autophagy and the epithelial–mesenchymal transition (EMT) was evaluated by qPCR and Western blotting. The transcriptome analysis was used to uncover the molecular mechanism of TGF-β2-induced PCO formation. Results: TGF-β2 specifically promotes autophagy flux in human lens epithelial cells. The activation of autophagy by rapamycin can promote EMT marker synthesis and improve cell migration. However, the inhibition of autophagy by 3-MA attenuates EMT. To uncover the molecular mechanisms, we performed RNA sequencing and found that TGF-β2 elevated tumor protein p53-inducible nuclear protein2 (TP53INP2) expression, which was accompanied by a nuclear-to-cytoplasm translocation. Moreover, the knockdown of TP53INP2 blocked the TGF-β2-induced autophagy and EMT processes, revealing that TP53INP2 plays an important role in TGF-β2-induced autophagy during EMT. Conclusions: Taken together, the results of this study suggested that TP53INP2 was a novel regulator of PCO development by TGF-β2, and notably, TP53INP2, may be a potential target for the pharmacological treatment of PCO.
Ni-Decorated ZnO Monolayer for Sensing CO and HCHO in Dry-Type Transformers: A First-Principles Theory
Authors: Zhang Jin , Wang Yuqing , Wei Zhuo , Wang Qi , Liang Zhengbo , Yuan Tian
Published: August 2022

This work implements first-principles simulations in order to investigate the Ni-decorating property on the ZnO monolayer and the sensing property of the Ni-decorated ZnO (Ni–ZnO) monolayer upon CO and HCHO molecules formed in the dry-type transformers. The results reveal that the Ni dopant is stably anchored on the TO site of the ZnO surface forming the Ni–Zn and Ni–O bonds with the binding energy (Eb) of −1.75 eV. Based on the adsorption energy (Ead) of −1.49 and −2.22 eV for CO and HCHO on the Ni–ZnO monolayer, we determined the chemisorption for two such systems. The band structure (BS) and atomic density of state (DOS) of the gas adsorbed systems are analyzed to comprehend the electronic property of the Ni–ZnO monolayer in the gas adsorptions. Besides, the change of bandgap and work function uncover the sensing potential of Ni–ZnO monolayer upon CO and HCHO detections, with admirable electrical response (15,394.9% and −84.6%). The findings in this work manifest the potential of Ni–ZnO monolayer for CO and HCHO sensing to evaluate the operation condition of the dry-type transformers.
Fenfluramine: A Review of Pharmacology, Clinical Efficacy, and Safety in Epilepsy
Authors: Samanta Debopam
Published: August 2022

Despite the availability of more than 30 antiseizure medications (ASMs), the proportion of patients who remain refractory to ASMs remains static. Refractory seizures are almost universal in patients with epileptic encephalopathies. Since many of these patients are not candidates for curative surgery, there is always a need for newer ASMs with better efficacy and safety profile. Recently, the anti-obesity medication fenfluramine (FFA) has been successfully repurposed, and various regulatory agencies approved it for seizures associated with Dravet and Lennox–Gastaut syndromes. However, there is a limited in-depth critical review of FFA to facilitate its optimal use in a clinical context. This narrative review discusses and summarizes the antiseizure mechanism of action of FFA, clinical pharmacology, and clinical studies related to epilepsy, focusing on efficacy and adverse effects.