bluuebunny/crossref_metadata_2025 huggingface dataset:
Modern Approaches to Lower Lipoprotein(a) Concentrations and Consequences for Cardiovascular Diseases
Authors: Korneva Victoria A. , Kuznetsova Tatjana Yurjevna , Julius Ulrich
Published: September 2021

Lipoprotein(a) (Lp(a)) is a low density lipoprotein particle that is associated with poor cardiovascular prognosis due to pro-atherogenic, pro-thrombotic, pro-inflammatory and pro-oxidative properties. Traditional lipid-lowering therapy does not provide a sufficient Lp(a) reduction. For PCSK9 inhibitors a small reduction of Lp(a) levels could be shown, which was associated with a reduction in cardiovascular events, independently of the effect on LDL cholesterol. Another option is inclisiran, for which no outcome data are available yet. Lipoprotein apheresis acutely and in the long run decreases Lp(a) levels and effectively improves cardiovascular prognosis in high-risk patients who cannot be satisfactorily treated with drugs. New drugs inhibiting the synthesis of apolipoprotein(a) (an antisense oligonucleotide (Pelacarsen) and two siRNA drugs) are studied. Unlike LDL-cholesterol, for Lp(a) no target value has been defined up to now. This overview presents data of modern capabilities of cardiovascular risk reduction by lowering Lp(a) level.
Platelet miRNA Biosignature Discriminates between Dementia with Lewy Bodies and Alzheimer’s Disease
Authors: Gámez-Valero Ana , Campdelacreu Jaume , Vilas Dolores , Ispierto Lourdes , Gascón-Bayarri Jordi , Reñé Ramón , Álvarez Ramiro , Armengol Maria P. , Borràs Francesc E. , Beyer Katrin
Published: September 2021

Dementia with Lewy bodies (DLB) is one of the most common causes of degenerative dementia, after Alzheimer’s disease (AD), and presents pathological and clinical overlap with both AD and Parkinson’s disease (PD). Consequently, only one in three DLB cases is diagnosed correctly. Platelets, previously related to neurodegeneration, contain microRNAs (miRNAs) whose analysis may provide disease biomarkers. Here, we profiled the whole platelet miRNA transcriptome from DLB patients and healthy controls. Differentially expressed miRNAs were further validated in three consecutive studies from 2017 to 2019 enrolling 162 individuals, including DLB, AD, and PD patients, and healthy controls. Results comprised a seven-miRNA biosignature, showing the highest diagnostic potential for the differentiation between DLB and AD. Additionally, compared to controls, two miRNAs were down-regulated in DLB, four miRNAs were up-regulated in AD, and two miRNAs were down-regulated in PD. Predictive target analysis identified three disease-specific clusters of pathways as a result of platelet-miRNA deregulation. Our cross-sectional study assesses the identification of a novel, highly specific and sensitive platelet-associated miRNA-based biosignature, which distinguishes DLB from AD.
Applications of Aptamer-Bound Nanomaterials in Cancer Therapy
Authors: Zhu Liangxi , Zhao Jingzhou , Guo Zhukang , Liu Yuan , Chen Hui , Chen Zhu , He Nongyue
Published: September 2021

Cancer is still a major disease that threatens human life. Although traditional cancer treatment methods are widely used, they still have many disadvantages. Aptamers, owing to their small size, low toxicity, good specificity, and excellent biocompatibility, have been widely applied in biomedical areas. Therefore, the combination of nanomaterials with aptamers offers a new method for cancer treatment. First, we briefly introduce the situation of cancer treatment and aptamers. Then, we discuss the application of aptamers in breast cancer treatment, lung cancer treatment, and other cancer treatment methods. Finally, perspectives on challenges and future applications of aptamers in cancer therapy are discussed.
Evaluation of Cancer Cell Lines by Four-Point Probe Technique, by Impedance Measurements in Various Frequencies
Authors: Paivana Georgia , Barmpakos Dimitris , Mavrikou Sophie , Kallergis Alexandros , Tsakiridis Odysseus , Kaltsas Grigoris , Kintzios Spyridon
Published: September 2021

Cell-based biosensors appear to be an attractive tool for the rapid, simple, and cheap monitoring of chemotherapy effects at a very early stage. In this study, electrochemical measurements using a four-point probe method were evaluated for suspensions of four cancer cell lines of different tissue origins: SK–N–SH, HeLa, MCF-7 and MDA-MB-231, all for two different population densities: 50 K and 100 K cells/500 μL. The anticancer agent doxorubicin was applied for each cell type in order to investigate whether the proposed technique was able to determine specific differences in cell responses before and after drug treatment. The proposed methodology can offer valuable insight into the frequency-dependent bioelectrical responses of various cellular systems using a low frequency range and without necessitating lengthy cell culture treatment. The further development of this biosensor assembly with the integration of specially designed cell/electronic interfaces can lead to novel diagnostic biosensors and therapeutic bioelectronics.
Diffusion-Based Separation of Extracellular Vesicles by Nanoporous Membrane Chip
Authors: Kim Gijung , Park Min Chul , Jang Seonae , Han Daeyoung , Kim Hojun , Kim Wonjune , Chun Honggu , Kim Sunghoon
Published: September 2021

Extracellular vesicles (EVs) have emerged as novel biomarkers and therapeutic material. However, the small size (~200 nm) of EVs makes efficient separation challenging. Here, a physical/chemical stress-free separation of EVs based on diffusion through a nanoporous membrane chip is presented. A polycarbonate membrane with 200 nm pores, positioned between two chambers, functions as the size-selective filter. Using the chip, EVs from cell culture media and human serum were separated. The separated EVs were analyzed by nanoparticle tracking analysis (NTA), scanning electron microscopy, and immunoblotting. The experimental results proved the selective separation of EVs in cell culture media and human serum. Moreover, the diffusion-based separation showed a high yield of EVs in human serum compared to ultracentrifuge-based separation. The EV recovery rate analyzed from NTA data was 42% for cell culture media samples. We expect the developed method to be a potential tool for EV separation for diagnosis and therapy because it does not require complicated processes such as immune, chemical reaction, and external force and is scalable by increasing the nanoporous membrane size.
Clinical Implications of Amyloid-Beta Accumulation in Occipital Lobes in Alzheimer’s Continuum
Authors: Hwang Jihye , Kim Chan Mi , Kim Ji Eun , Oh Minyoung , Oh Jungsu S. , Yoon Young Wook , Kim Jae Seung , Lee Jae-Hong , Roh Jee Hoon
Published: September 2021

A substantial amount of amyloid-beta (Aβ) accumulates in the occipital cortices; however, it draws less attention. We investigated the clinical implications of Aβ accumulation in the occipital lobes in the Alzheimer’s disease (AD) continuum. [18F]-Florbetaben amyloid PET scans were performed in a total of 121 AD or amnestic mild cognitive impairment (aMCI) patients. Of the 121 patients, 74 Aβ positive patients were divided into occipital Aβ positive (OCC+) and occipital Aβ negative (OCC−) groups based on Aβ accumulation in the bilateral occipital lobes. The OCC+ group (41/74, 55.4%) was younger and had a younger age at onset than the OCC− group. The OCC+ group also had an increased standard uptake value ratio in the occipital lobes and greater cortical thinning in relevant areas. The OCC+ group had a higher global deterioration scale, lower performance for the copy, immediate recall, delayed recall, and recognition in Rey–Osterrieth Complex Figure tests than the OCC- group, although both groups had similar disease durations. AD or aMCI patients in the OCC+ group exhibited features noted in early onset AD with relevant neuropsychological and image findings. Occipital Aβ positivity in amyloid PET scans need to be considered as an underestimated marker of early onset AD continuum.
Does Real-Time Feedback Affect Sensorimotor EEG Patterns in Routine Motor Imagery Practice?
Authors: Vasilyev Anatoly N. , Nuzhdin Yury O. , Kaplan Alexander Y.
Published: September 2021

Background. Motor imagery engages much of the same neural circuits as an overt movement. Therefore, the mental rehearsal of movements is often used to supplement physical training and might aid motor neurorehabilitation after stroke. One attempt to capture the brain’s involvement in imagery involves the use, as a marker, of the depression or event-related desynchronization (ERD) of thalamocortical sensorimotor rhythms found in a human electroencephalogram (EEG). Using fast real-time processing, it is possible to make the subject aware of their own brain reactions or—even better—to turn them into actions through a technology called the brain–computer interface (BCI). However, it remains unclear whether BCI-enabled imagery facilitates a stronger or qualitatively different brain response compared to the open-loop training. Methods. Seven healthy volunteers who were experienced in both closed and open-loop motor imagery took part in six experimental sessions over a period of 4.5 months, in which they performed kinesthetic imagery of a previously known set of finger and arm movements with simultaneous 30-channel EEG acquisition. The first and the last session mostly consisted of feedback trials in which the subjects were presented with the classification results of the EEG patterns in real time; during the other sessions, no feedback was provided. Spatiotemporal and amplitude features of the ERD patterns concomitant with imagery were compared across experimental days and between feedback conditions using linear mixed-effects modeling. Results. The main spatial sources of ERD appeared to be highly stable across the six experimental days, remaining nearly identical in five of seven subjects (Pearson’s ρ > 0.94). Only in one subject did the spatial pattern of activation statistically significantly differ (p = 0.009) between the feedback and no-feedback conditions. Real-time visual feedback delivered through the BCI did not significantly increase the ERD strength. Conclusion. The results imply that the potential benefits of MI could be yielded by well-habituated subjects with a simplified open-loop setup, e.g., through at-home self-practice.
A Diagnostic Dilemma of White Matter Lesions and Cerebral Oedema without Identifiable Cause—A Neurological Conundrum
Authors: Goire Namraj , Buckland Michael , Cuganesan Ramesh , Saleem Sameer , Lea Vivienne , Beran Roy G
Published: September 2021

Introduction: This paper describes a case of bi-frontal vasogenic oedema associated with bilateral frontal lobe and left parietal lobe white matter lesions where extensive investigations, including brain biopsy, failed to establish a diagnosis. Case Report: A 67-year-old female presented with three weeks’ history of memory loss, fatigue, insomnia, nausea, and occasional dysphasia. Physical examination was unremarkable, yet cerebral CT and MRI showed bilateral frontal lobe vasogenic oedema. Extensive investigations, including: biochemical; radiological; immunological; microbiological; haematological; histopathological; and cytological, failed to establish a confirmed diagnosis. A multidisciplinary team could not achieve a consensus for this atypical presentation. Brain biopsy was unusual, showing destructive inflammatory and subtly granulomatous disease, but an exhaustive list of auxiliary tests could not confirm a cause, and consensus favoured glial fibrillary acidic protein (GFAP) autoimmune encephalopathy. Discussion: A definitive diagnosis could not be established for this patient despite a gamut of investigations. Although some of the presenting features were consistent with GFAP astrocytopathy, initial staining of the patient’s CSF for neuronal antibodies was negative. Her symptoms and radiological changes of brain imaging improved without any corticosteroid therapy. Conclusions: Through this case report, the aim is to add to the repository of neurological sciences in the hope that future similar presentations could potentially lead to discovery of a new aetiology or contribute towards better understanding of an existing disease process.
Minimally Invasive L5 Corpectomy with Navigated Expandable Vertebral Cage: A Technical Note
Authors: Yamauchi Taro , Jaiswal Ashish , Tanaka Masato , Fujiwara Yoshihiro , Oda Yoshiaki , Arataki Shinya , Misawa Haruo
Published: September 2021

Background: Conventional L5 corpectomy requires a large incision and an extended period of intraoperative fluoroscopy. We describe herein a new L5 corpectomy technique. Methods: A 79-year-old woman was referred to our hospital for leg pain and lower back pain due to an L5 vertebral fracture. Her daily life had been affected by severe lower back pain and sciatica for more than 2 months. We initially performed simple decompression surgery, but this proved effective for only 10 months. Results: For revision surgery, the patient underwent minimally invasive L5 corpectomy with a navigated expandable cage without fluoroscopy. The second surgery took 215 min, and estimated blood loss was 750 mL. The revision surgery proved successful, and the patient could then walk using a cane. In terms of clinical outcomes, the Oswestry Disability Index improved from 66% to 24%, and the visual analog scale score for lower back pain improved from 84 to 31 mm at the 1-year follow-up. Conclusions: Minimally invasive L5 corpectomy with a navigated expandable vertebral cage is effective for reducing cage misplacement and surgical invasiveness. With this new technique, surgeons and operating room staff can avoid the risk of adverse events due to intraoperative radiation exposure.
A Multilevel Approach to Explore the Wandering Mind and Its Connections with Mindfulness and Personality
Authors: Cantone Damiano , Feruglio Susanna , Crescentini Cristiano , Cinot Sabrina , Matiz Alessio
Published: September 2021

We propose an innovative approach to study Mind Wandering (MW), and we present an application of this methodology to study the effects of a Mindfulness-Oriented Meditation (MOM) training. We assessed individuals’ MW through a free association task and an attentional task with thought-probes combined with a questionnaire for the phenomenological characteristic of each MW episode. We used the Temperament and Character Inventory to assess participants’ personality traits and their associations with measures of MW. Our study was limited by the course of the Covid-19 pandemic and only nine healthy young individuals completed the testing sessions, which were carried out before and after the MOM training. After MOM, participants showed fewer repetitive and self-relevant thoughts and indices of better performance in the attentional task; the linguistic analysis of participants’ free associations showed lower verbal productivity and a decrease in utterances that expressed anxiety/stress. Overall, we foresee that future studies could replicate our preliminary findings with larger samples and in a period without a global health emergency. This multilevel approach to the study of MW may allow researchers to gain a broader view of the phenomenon, considering its occurrence, qualitative characteristics, impact on cognitive tasks, malleability via mindfulness or other psychological interventions, and relations with personality traits.
Test and Evaluation of the Flexural Properties of Reinforced Concrete Beams with 100% Recycled Coarse Aggregate and Manufactured Sand
Authors: Li Changyong , Liu Tongsheng , Fu Hao , Zhang Xiaoyan , Yang Yabin , Zhao Shunbo
Published: September 2021

Although studies have been performed on the recycled aggregate made of waste concrete for the production of new concrete, the new concrete with 100% recycled coarse aggregate and manufactured sand (abbreviated as RAMC) still needs to be researched for structural applications. In this paper, an experimental study was performed on seven groups, including fourteen reinforced RAMC beams under the simply supported four-point loading test, considering the factors of the strength of RAMC and the reinforcement ratio of longitudinal tensile rebars. Based on the test results, the cracking resistance, the bearing capacity, the crack width, the flexural stiffness and the mid-span deflection of reinforced RAMC beams in bending are discussed and examined by using the formulas of conventional reinforced concrete beams. Results show that an obvious effect of reinforcement ratio was present, while less so was that of the strength of RAMC. With the comparison of predicted values by the formulas of conventional reinforced concrete beams, the reinforced RAMC beams decreased cracking resistance by about 20%, increased crack width by about 15% and increased mid-span deflection by about 10%, although the same bearing capacity can be reached. The results directly relate to the lower tensile strength of RAMC which should be further improved.
The Multiple Faces of MNT and Its Role as a MYC Modulator
Authors: Liaño-Pons Judit , Arsenian-Henriksson Marie , León Javier
Published: September 2021

MNT is a crucial modulator of MYC, controls several cellular functions, and is activated in most human cancers. It is the largest, most divergent, and most ubiquitously expressed protein of the MXD family. MNT was first described as a MYC antagonist and tumor suppressor. Indeed, 10% of human tumors present deletions of one MNT allele. However, some reports show that MNT functions in cooperation with MYC by maintaining cell proliferation, promoting tumor cell survival, and supporting MYC-driven tumorigenesis in cellular and animal models. Although MAX was originally considered MNT’s obligate partner, our recent findings demonstrate that MNT also works independently. MNT forms homodimers and interacts with proteins both outside and inside of the proximal MYC network. These complexes are involved in a wide array of cellular processes, from transcriptional repression via SIN3 to the modulation of metabolism through MLX as well as immunity and apoptosis via REL. In this review, we discuss the present knowledge of MNT with a special focus on its interactome, which sheds light on the complex and essential role of MNT in cell biology.
Prostate Cancer—Focus on Cholesterol
Authors: Škara Lucija , Huđek Turković Ana , Pezelj Ivan , Vrtarić Alen , Sinčić Nino , Krušlin Božo , Ulamec Monika
Published: September 2021

Prostate cancer (PC) is the most common malignancy in men. Common characteristic involved in PC pathogenesis are disturbed lipid metabolism and abnormal cholesterol accumulation. Cholesterol can be further utilized for membrane or hormone synthesis while cholesterol biosynthesis intermediates are important for oncogene membrane anchoring, nucleotide synthesis and mitochondrial electron transport. Since cholesterol and its biosynthesis intermediates influence numerous cellular processes, in this review we have described cholesterol homeostasis in a normal cell. Additionally, we have illustrated how commonly deregulated signaling pathways in PC (PI3K/AKT/MTOR, MAPK, AR and p53) are linked with cholesterol homeostasis regulation.
Characteristics of Selected Adipokines in Ascites and Blood of Ovarian Cancer Patients
Authors: Wróblewski Marcin , Szewczyk-Golec Karolina , Hołyńska-Iwan Iga , Wróblewska Joanna , Woźniak Alina
Published: September 2021

Ovarian cancer is one of the most common malignancies among women worldwide. The course of the disease is often latent and asymptomatic in the early stages, but as it develops, metastasis occurs, accompanied by accumulation of ascites in the peritoneal cavity. The ascites fluid constitutes a specific microenvironment influencing the processes of carcinogenesis. In ascites, signaling is mediated by various cytokines that control tumor cell proliferation, progression, metastasis, and chemoresistance. Adipokines, secreted into ascites and also appearing in blood, may be markers of ongoing processes related to the development of neoplastic disease. Moreover, a significant influence of adipocyte lipids on the growth of tumors, for which they are one of energy sources, is observed. Adiponectin, interleukin 6 (IL-6), interleukin 8 (IL-8), monocyte chemotactic protein-1 (MCP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1), discussed in the present review, were found to mediate the effects of omentum metastasis through homing, migration and invasion of ovarian cancer cells. Further research on those adipokines seem to be a natural consequence, allowing for a better understanding of the mechanisms of neoplastic disease and determination of the treatment procedure.
The Multifaceted Role of Aldehyde Dehydrogenases in Prostate Cancer Stem Cells
Authors: Püschel Jakob , Dubrovska Anna , Gorodetska Ielizaveta
Published: September 2021

Cancer stem cells (CSCs) are the only tumor cells possessing self-renewal and differentiation properties, making them an engine of tumor progression and a source of tumor regrowth after treatment. Conventional therapies eliminate most non-CSCs, while CSCs often remain radiation and drug resistant, leading to tumor relapse and metastases. Thus, targeting CSCs might be a powerful tool to overcome tumor resistance and increase the efficiency of current cancer treatment strategies. The identification and isolation of the CSC population based on its high aldehyde dehydrogenase activity (ALDH) is widely accepted for prostate cancer (PCa) and many other solid tumors. In PCa, several ALDH genes contribute to the ALDH activity, which can be measured in the enzymatic assay by converting 4, 4-difluoro-4-bora-3a, 4a-diaza-s-indacene (BODIPY) aminoacetaldehyde (BAAA) into the fluorescent product BODIPY-aminoacetate (BAA). Although each ALDH isoform plays an individual role in PCa biology, their mutual functional interplay also contributes to PCa progression. Thus, ALDH proteins are markers and functional regulators of CSC properties, representing an attractive target for cancer treatment. In this review, we discuss the current state of research regarding the role of individual ALDH isoforms in PCa development and progression, their possible therapeutic targeting, and provide an outlook for the future advances in this field.
Preparation of Extremely Active Ethylene Tetramerization Catalyst [iPrN(PAr2)2−CrCl2]+[B(C6F5)4]– (Ar = −C6H4-p-SiR3)
Authors: Lee Jung Hyun , Baek Jun Won , Lee Dong Geun , Ko Ji Hyeong , Lee Dong Geun , Cho Kye Sung , Lee Jin Woo , Lee Bun Yeoul
Published: September 2021

Numerous efforts have been made to achieve “on-purpose” 1-octene production since Sasol discovered a Cr-based selective ethylene tetramerization catalyst in the early 2000s. By preparing a series of bis(phosphine) ligands iPrN(PAr2)2 where the Ar contains a bulky –SiR3 substituent (Ar = −C6H4-p-Si(nBu)3 (1), −C6H4-p-Si(1-hexyl)3 (2), −C6H4-p-Si(1-octyl)3 (3), −C6H4-p-Si(2-ethylhexyl)3 (4), −C6H4-p-Si(3,7-dimethyloctyl)3 (5)), we obtained an extremely active catalyst that meets the criteria for commercial utilization. The Cr complexes [iPrN(PAr2)2−CrCl2]+[B(C6F5)4]–, obtained by reacting ligands 1–5 with [(CH3CN)4CrCl2]+[B(C6F5)4]–, showed high activity exceeding 6000 kg/g-Cr/h, when combined with the inexpensive iBu3Al, thus avoiding the use of expensive modified methylaluminoxane (MMAO). The bulky –SiR3 substituents played a key role in the success of catalysis by blocking the formation of inactive species (Cr complexes coordinated by two iPrN(PAr2)2 ligands, that is, [(iPrN(PAr2)2)2−CrCl2]+[B(C6F5)4]–). Among the complexes prepared, [3−CrCl2]+[B(C6F5)4]– exhibited the highest activity (11,100 kg/g-Cr/h, 100 kg/g-catalyst) with high 1-octene selectivity (75 wt%) and, moreover, mitigated the generation of undesired > C10 fractions (10.7 wt%). A 10-g-scale synthesis of 3 was developed, as well as a facile and low-cost synthetic method for [(CH3CN)4CrCl2]+[B(C6F5)4]–.
Synthesis of Catalytic Ni/Cu Nanoparticles from Simulated Wastewater on Li–Al Mixed Metal Oxides for a Two-Stage Catalytic Process in Ethanol Steam Reforming: Catalytic Performance and Coke Properties
Authors: Chen Yu-Jia , Huang Song-Hui , Uan Jun-Yen , Lin Hao-Tung
Published: September 2021

This work recovered Ni or Cu cations from simulated electroplating wastewater to synthesize Ni/Cu nano-catalysts for H2 generation by ethanol steam reforming (ESR). Aluminum lathe waste was used as a framework to prepare the structured catalyst. Li–Al–CO3 layered double hydroxide (LDH) was electrodeposited on the surface of the framework. The LDH was in a platelet-like structure, working as a support for the formation of the precursor of the metal catalysts. The catalytic performance and the coke properties of a 6Cu_6Ni two-stage catalyst configuration herein used for ESR catalytic reaction were studied. The Cu–Ni two-stage catalyst configuration (6Cu_6Ni) yielded more H2 (~10%) than that by using the Ni-based catalyst (6Ni) only. The 6Cu_6Ni catalyst configuration also resulted in a relatively stable H2 generation rate vs. time, with nearly no decline during the 5-h reaction. Through the pre-reaction of ethanol-steam mixture with Cu/LiAlO2 catalyst, the Ni/LiAlO2 catalyst in the 6Cu_6Ni catalyst configuration could steadily decompose acetaldehyde, and rare acetate groups, which would evolve condensed coke, were formed. The Ni nanoparticles were observed to be lifted and separated by the carbon filaments from the support and had no indication of sintering, contributing to the bare deactivation of the Ni/LiAlO2 catalyst in 6Cu_6Ni.
Photocatalytic Removal of Pharmaceuticals from Greywater
Authors: Ojobe Bukola , Zouzelka Radek , Satkova Barbora , Vagnerova Magdalena , Nemeskalova Alzbeta , Kuchar Martin , Bartacek Jan , Rathousky Jiri
Published: September 2021

High concentrations of pharmaceuticals have been detected in greywater effluents treated using up-to-date technologies. Finding a suitable additional treatment before this effluent is reused is urgently needed to ensure the reused water meets quality standards. This paper reports the use of heterogeneous photocatalysis on anatase and rutile nanopowders to remove naproxen, metformin and sulfamethoxazole, at practically relevant concentrations found in membrane bioreactor (MBR)-treated greywater. A low anatase concentration of 400 mg L−1 was sufficient to efficiently degrade the pharmaceuticals listed above, with complete degradation observed in 5 h. The effect of background species presented in greywater was, to some extent, comparable to that of the OH-radical scavenger. These results prove that photocatalysis using anatase TiO2 is a feasible additional treatment for greywater recycling.
Engineering of a Novel, Magnetic, Bi-Functional, Enzymatic Nanobiocatalyst for the Highly Efficient Synthesis of Enantiopure (R)-3-quinuclidinol
Authors: Li Qingman , Jiang Qihua , Gu Pengcheng , Ma Lianju , Wang Yiwu
Published: September 2021

Ni2+-NTA-boosted magnetic porous silica nanoparticles (Ni@MSN) to serve as ideal support for bi-functional enzyme were fabricated for the first time. The versatility of this support was validated by one-step purification and immobilization of bi-functional enzyme MLG consisting of 3-Quinuclidinone reductase and glucose dehydrogenase, which can simultaneously catalyze both carbonyl reduction and cofactor regeneration, to fabricate an artificial bi-functional nanobiocatalyst (namely, MLG-Ni@MSN). The enzyme loading of 71.7 mg/g support and 92.7% immobilization efficiency were obtained. Moreover, the immobilized MLG showed wider pH and temperature tolerance and greater storage stability than free MLG under the same conditions. The nanosystem was employed as biocatalyst to accomplish the 3-quinuclidinone (70 g/L) to (R)-3-quinuclidinol biotransformation in 100% conversion yield with >99% selectivity within 6 h and simultaneous cofactor regeneration. Furthermore, the immobilized MLG retained up to 80.3% (carbonyl reduction) and 78.0% (cofactor regeneration) of the initial activity after being recycled eight times. In addition, the MLG-Ni@MSN system exhibited almost no enzyme leaching during biotransformation and recycling. Therefore, we have reason to believe that the Ni@MSN support gave great promise for constructing a new biocatalytic nanosystem with multifunctional enzymes to achieve some other complex bioconversions.
Assembly of CaIn2S4 on Defect-Rich BiOCl for Acceleration of Interfacial Charge Separation and Photocatalytic Phenol Degradation via S-Scheme Electron Transfer Mechanism
Authors: Zhang Zhuangzhuang , Zhang Yuanyuan , Han Xuanxuan , Guo Li , Wang Danjun , Lv Kangle
Published: September 2021

The novel 2D/2D S-scheme heterostructure of BiOCl nanosheets coupled with CaIn2S4 nanosheets (CaIn2S4/BiOCl-SOVs), which contains surface oxygen vacancies (SOVs), has been successfully prepared by high-temperature calcination combined with a solvothermal synthetic strategy. Under visible-light irradiation, the apparent rate constant (Kapp/mim−1) for phenol degradation on the 1 wt% CaIn2S4/BiOCl-SOVs photocatalyst is about 32.8 times higher than that of pure BiOCl. The superior performance was attributed to the synergistic effect between the SOVs, CaIn2S4, and BiOCl, which can effectively narrow the bandgap and accelerate the interfacial charge separation of CaIn2S4/BiOCl-SOVs heterojunctions. Subsequently, it significantly promotes the generation of superoxide radicals (O2−), hydroxyl radicals, and h+, which participate in the photodegradation process of phenol. The catalyst still maintained a relatively high activity after repeated tests as a demonstration of its photostability. This work successfully proposed an efficient method to design a new 2D/2D S-scheme heterostructure with SOVs as possible photocatalysts in the field of environmental remediation.
Mitochondrial Biogenesis, Mitochondrial Dynamics, and Mitophagy in the Maturation of Cardiomyocytes
Authors: Ding Qianqian , Qi Yanxiang , Tsang Suk-Ying
Published: September 2021

Pluripotent stem cells (PSCs) can undergo unlimited self-renewal and can differentiate into all the cell types present in our body, including cardiomyocytes. Therefore, PSCs can be an excellent source of cardiomyocytes for future regenerative medicine and medical research studies. However, cardiomyocytes obtained from PSC differentiation culture are regarded as immature structurally, electrophysiologically, metabolically, and functionally. Mitochondria are organelles responsible for various cellular functions such as energy metabolism, different catabolic and anabolic processes, calcium fluxes, and various signaling pathways. Cells can respond to cellular needs to increase the mitochondrial mass by mitochondrial biogenesis. On the other hand, cells can also degrade mitochondria through mitophagy. Mitochondria are also dynamic organelles that undergo continuous fusion and fission events. In this review, we aim to summarize previous findings on the changes of mitochondrial biogenesis, mitophagy, and mitochondrial dynamics during the maturation of cardiomyocytes. In addition, we intend to summarize whether changes in these processes would affect the maturation of cardiomyocytes. Lastly, we aim to discuss unanswered questions in the field and to provide insights for the possible strategies of enhancing the maturation of PSC-derived cardiomyocytes.
The Atypical Cyclin-Dependent Kinase 5 (Cdk5) Guards Podocytes from Apoptosis in Glomerular Disease While Being Dispensable for Podocyte Development
Authors: Mangold Nicole , Pippin Jeffrey , Unnersjoe-Jess David , Koehler Sybille , Shankland Stuart , Brähler Sebastian , Schermer Bernhard , Benzing Thomas , Brinkkoetter Paul T. , Hagmann Henning
Published: September 2021

Cyclin-dependent kinase 5 (Cdk5) is expressed in terminally differentiated cells, where it drives development, morphogenesis, and survival. Temporal and spatial kinase activity is regulated by specific activators of Cdk5, dependent on the cell type and environmental factors. In the kidney, Cdk5 is exclusively expressed in terminally differentiated glomerular epithelial cells called podocytes. In glomerular disease, signaling mechanisms via Cdk5 have been addressed by single or combined conventional knockout of known specific activators of Cdk5. A protective, anti-apoptotic role has been ascribed to Cdk5 but not a developmental phenotype, as in terminally differentiated neurons. The effector kinase itself has never been addressed in animal models of glomerular disease. In the present study, conditional and inducible knockout models of Cdk5 were analyzed to investigate the role of Cdk5 in podocyte development and glomerular disease. While mice with podocyte-specific knockout of Cdk5 had no developmental defects and regular lifespan, loss of Cdk5 in podocytes increased susceptibility to glomerular damage in the nephrotoxic nephritis model. Glomerular damage was associated with reduced anti-apoptotic signals in Cdk5-deficient mice. In summary, Cdk5 acts primarily as master regulator of podocyte survival during glomerular disease and—in contrast to neurons—does not impact on glomerular development or maintenance.
Parthenogenesis and the Evolution of Anisogamy
Authors: Constable George W. A. , Kokko Hanna
Published: September 2021

Recently, it was pointed out that classic models for the evolution of anisogamy do not take into account the possibility of parthenogenetic reproduction, even though sex is facultative in many relevant taxa (e.g., algae) that harbour both anisogamous and isogamous species. Here, we complement this recent analysis with an approach where we assume that the relationship between progeny size and its survival may differ between parthenogenetically and sexually produced progeny, favouring either the former or the latter. We show that previous findings that parthenogenesis can stabilise isogamy relative to the obligate sex case, extend to our scenarios. We additionally investigate two different ways for one mating type to take over the entire population. First, parthenogenesis can lead to biased sex ratios that are sufficiently extreme that one type can displace the other, leading to de facto asexuality for the remaining type that now lacks partners to fuse with. This process involves positive feedback: microgametes, being numerous, lack opportunities for syngamy, and should they proliferate parthenogenetically, the next generation makes this asexual route even more prominent for microgametes. Second, we consider mutations to strict asexuality in producers of micro- or macrogametes, and show that the prospects of asexual invasion depend strongly on the mating type in which the mutation arises. Perhaps most interestingly, we also find scenarios in which parthenogens have an intrinsic survival advantage yet facultatively sexual isogamous populations are robust to the invasion of asexuals, despite us assuming no genetic benefits of recombination. Here, equal contribution from both mating types to zygotes that are sufficiently well provisioned can outweigh the additional costs associated with syngamy.
Sperm Accumulation Induced by the Female Reproductive Fluid: Putative Evidence of Chemoattraction Using a New Tool
Authors: Devigili Alessandro , Cattelan Silvia , Gasparini Clelia
Published: September 2021

There is considerable evidence that female reproductive fluid (FRF) interacts intimately with sperm, affecting several sperm traits, including sperm motility and longevity, and ultimately fertilization success. One of the first documented interactions between FRF and sperm is the ability of FRF to attract and guide sperm towards the eggs. However, most of the evidence of FRF’s chemoattraction proprieties comes from a limited number of taxa, specifically mammals and invertebrate broadcasting spawners. In other species, small FRF volumes and/or short sperm longevity often impose methodological difficulties resulting in this gap in chemoattraction studies in non-model species. One of the outcomes of sperm chemotaxis is sperm accumulation towards high chemoattractant concentrations, which can be easily quantified by measuring sperm concentration. Here, we tested sperm accumulation towards FRF in the zebrafish, Danio rerio, using an ad hoc developed, 3D printed, device (‘sperm selection chamber’). This easy-to-use tool allows to select and collect the sperm that swim towards a chemical gradient, and accumulate in a chemoattractant-filled well thus providing putative evidence for chemoattraction. We found that sperm accumulate in FRF in zebrafish. We also found that none of the sperm quality traits we measured (sperm swimming velocity and trajectory, sperm motility, and longevity) were correlated with this response. Together with the 3D printable project, we provide a detailed protocol for using the selection chamber. The chamber is optimized for the zebrafish, but it can be easily adapted for other species. Our device lays the foundation for a standardized way to measure sperm accumulation and in general chemoattraction, stimulating future research aimed at understanding the role and the mechanisms of sperm chemoattraction by FRF.
P-Rex1 Controls Sphingosine 1-Phosphate Receptor Signalling, Morphology, and Cell-Cycle Progression in Neuronal Cells
Authors: Hampson Elizabeth , Tsonou Elpida , Baker Martin J. , Hornigold David C. , Hubbard Roderick E. , Massey Andrew , Welch Heidi C. E.
Published: September 2021

P-Rex1 is a guanine-nucleotide exchange factor (GEF) that activates Rac-type small G proteins in response to the stimulation of a range of receptors, particularly G protein-coupled receptors (GPCRs), to control cytoskeletal dynamics and other Rac-dependent cell responses. P-Rex1 is mainly expressed in leukocytes and neurons. Whereas its roles in leukocytes have been studied extensively, relatively little is known about its functions in neurons. Here, we used CRISPR/Cas9-mediated P-Rex1 deficiency in neuronal PC12 cells that stably overexpress the GPCR S1PR1, a receptor for sphingosine 1-phosphate (S1P), to investigate the role of P-Rex1 in neuronal GPCR signalling and cell responses. We show that P-Rex1 is required for the S1P-stimulated activation of Rac1 and Akt, basal Rac3 activity, and constitutive cAMP production in PC12-S1PR1 cells. The constitutive cAMP production was not due to increased expression levels of major neuronal adenylyl cyclases, suggesting that P-Rex1 may regulate adenylyl cyclase activity. P-Rex1 was required for maintenance of neurite protrusions and spreading in S1P-stimulated PC12-S1PR1 cells, as well as for cell-cycle progression and proliferation. In summary, we identified novel functional roles of P-Rex1 in neuronal Rac, Akt and cAMP signalling, as well as in neuronal cell-cycle progression and proliferation.
Detection of Novel Potential Regulators of Stem Cell Differentiation and Cardiogenesis through Combined Genome-Wide Profiling of Protein-Coding Transcripts and microRNAs
Authors: Machado Rui , Sachinidis Agapios , Futschik Matthias E.
Published: September 2021

In vitro differentiation of embryonic stem cells (ESCs) provides a convenient basis for the study of microRNA-based gene regulation that is relevant for early cardiogenic processes. However, to which degree insights gained from in vitro differentiation models can be readily transferred to the in vivo system remains unclear. In this study, we profiled simultaneous genome-wide measurements of mRNAs and microRNAs (miRNAs) of differentiating murine ESCs (mESCs) and integrated putative miRNA-gene interactions to assess miRNA-driven gene regulation. To identify interactions conserved between in vivo and in vitro, we combined our analysis with a recent transcriptomic study of early murine heart development in vivo. We detected over 200 putative miRNA–mRNA interactions with conserved expression patterns that were indicative of gene regulation across the in vitro and in vivo studies. A substantial proportion of candidate interactions have been already linked to cardiogenesis, supporting the validity of our approach. Notably, we also detected miRNAs with expression patterns that closely resembled those of key developmental transcription factors. The approach taken in this study enabled the identification of miRNA interactions in in vitro models with potential relevance for early cardiogenic development. Such comparative approaches will be important for the faithful application of stem cells in cardiovascular research.
Exercise and Sestrin Mediate Speed and Lysosomal Activity in Drosophila by Partially Overlapping Mechanisms
Authors: Sujkowski Alyson , Wessells Robert
Published: September 2021

Chronic exercise is widely recognized as an important contributor to healthspan in humans and in diverse animal models. Recently, we have demonstrated that Sestrins, a family of evolutionarily conserved exercise-inducible proteins, are critical mediators of exercise benefits in flies and mice. Knockout of Sestrins prevents exercise adaptations to endurance and flight in Drosophila, and similarly prevents benefits to endurance and metabolism in exercising mice. In contrast, overexpression of dSestrin in muscle mimics several of the molecular and physiological adaptations characteristic of endurance exercise. Here, we extend those observations to examine the impact of dSestrin on preserving speed and increasing lysosomal activity. We find that dSestrin is a critical factor driving exercise adaptations to climbing speed, but is not absolutely required for exercise to increase lysosomal activity in Drosophila. The role of Sestrin in increasing speed during chronic exercise requires both the TORC2/AKT axis and the PGC1α homolog spargel, while dSestrin requires interactions with TORC1 to cell-autonomously increase lysosomal activity. These results highlight the conserved role of Sestrins as key factors that drive diverse physiological adaptations conferred by chronic exercise.
Muscle-Related Plectinopathies
Authors: Zrelski Michaela M. , Kustermann Monika , Winter Lilli
Published: September 2021

Plectin is a giant cytoskeletal crosslinker and intermediate filament stabilizing protein. Mutations in the human plectin gene (PLEC) cause several rare diseases that are grouped under the term plectinopathies. The most common disorder is autosomal recessive disease epidermolysis bullosa simplex with muscular dystrophy (EBS-MD), which is characterized by skin blistering and progressive muscle weakness. Besides EBS-MD, PLEC mutations lead to EBS with nail dystrophy, EBS-MD with a myasthenic syndrome, EBS with pyloric atresia, limb-girdle muscular dystrophy type R17, or EBS-Ogna. In this review, we focus on the clinical and pathological manifestations caused by PLEC mutations on skeletal and cardiac muscle. Skeletal muscle biopsies from EBS-MD patients and plectin-deficient mice revealed severe dystrophic features with variation in fiber size, degenerative myofibrillar changes, mitochondrial alterations, and pathological desmin-positive protein aggregates. Ultrastructurally, PLEC mutations lead to a disorganization of myofibrils and sarcomeres, Z- and I-band alterations, autophagic vacuoles and cytoplasmic bodies, and misplaced and degenerating mitochondria. We also summarize a variety of genetically manipulated mouse and cell models, which are either plectin-deficient or that specifically lack a skeletal muscle-expressed plectin isoform. These models are powerful tools to study functional and molecular consequences of PLEC defects and their downstream effects on the skeletal muscle organization.
Assessment and Validation of Globodera pallida as a Novel In Vivo Model for Studying Alzheimer’s Disease
Authors: Althobaiti Norah A. , Menaa Farid , Albalawi Aishah E. , Dalzell Johnathan J. , Warnock Neil D. , Mccammick Erin M. , Alsolais Abdulellah , Alkhaibari Abeer M. , Green Brian D.
Published: September 2021

Background: Whole transgenic or non-transgenic organism model systems allow the screening of pharmacological compounds for protective actions in Alzheimer’s disease (AD). Aim: In this study, a plant parasitic nematode, Globodera pallida, which assimilates intact peptides from the external environment, was investigated as a new potential non-transgenic model system of AD. Methods: Fresh second-stage juveniles of G. pallida were used to measure their chemosensory, perform immunocytochemistry on their neurological structures, evaluate their survival rate, measure reactive oxygen species, and determine total oxidized glutathione to reduced glutathione ratio (GSSG/GSH) levels, before and after treatment with 100 µM of various amyloid beta (Aβ) peptides (1–40, 1–42, 17–42, 17–40, 1–28, or 1–16). Wild-type N2 C. elegans (strain N2) was cultured on Nematode Growth Medium and directly used, as control, for chemosensory assays. Results: We demonstrated that: (i) G. pallida (unlike Caenorhabditis elegans) assimilates amyloid-β (Aβ) peptides which co-localise with its neurological structures; (ii) pre-treatment with various Aβ isoforms (1–40, 1–42, 17–42, 17–40, 1–28, or 1–16) impairs G. pallida’s chemotaxis to differing extents; (iii) Aβ peptides reduced survival, increased the production of ROS, and increased GSSG/GSH levels in this model; (iv) this unique model can distinguish differences between different treatment concentrations, durations, and modalities, displaying good sensitivity; (v) clinically approved neuroprotective agents were effective in protecting G. pallida from Aβ (1–42) exposure. Taken together, the data indicate that G. pallida is an interesting in vivo model with strong potential for discovery of novel bioactive compounds with anti-AD activity.
Potential Therapeutic Candidates for Age-Related Macular Degeneration (AMD)
Authors: Nashine Sonali
Published: September 2021

Aging contributes to the risk of development of ocular diseases including, but not limited to, Age-related Macular Degeneration (AMD) that is a leading cause of blindness in the United States as well as worldwide. Retinal aging, that contributes to AMD pathogenesis, is characterized by accumulation of drusen deposits, alteration in the composition of Bruch’s membrane and extracellular matrix, vascular inflammation and dysregulation, mitochondrial dysfunction, and accumulation of reactive oxygen species (ROS), and subsequent retinal pigment epithelium (RPE) cell senescence. Since there are limited options available for the prophylaxis and treatment of AMD, new therapeutic interventions are constantly being looked into to identify new therapeutic targets for AMD. This review article discusses the potential candidates for AMD therapy and their known mechanisms of cytoprotection in AMD. These target therapeutic candidates include APE/REF-1, MRZ-99030, Ciliary NeuroTrophic Factor (CNTF), RAP1 GTPase, Celecoxib, and SS-31/Elamipretide.