bluuebunny/crossref_metadata_2025 huggingface dataset:
Contrast-Enhancing Lesion Segmentation in Multiple Sclerosis: A Deep Learning Approach Validated in a Multicentric Cohort
Authors: Greselin Martina , Lu Po-Jui , Melie-Garcia Lester , Ocampo-Pineda Mario , Galbusera Riccardo , Cagol Alessandro , Weigel Matthias , de Oliveira Siebenborn Nina , Ruberte Esther , Benkert Pascal , Müller Stefanie , Finkener Sebastian , Vehoff Jochen , Disanto Giulio , Findling Oliver , Chan Andrew , Salmen Anke , Pot Caroline , Bridel Claire , Zecca Chiara , Derfuss Tobias , Lieb Johanna M. , Diepers Michael , Wagner Franca , Vargas Maria I. , Pasquier Renaud Du , Lalive Patrice H. , Pravatà Emanuele , Weber Johannes , Gobbi Claudio , Leppert David , Kim Olaf Chan-Hi , Cattin Philippe C. , Hoepner Robert , Roth Patrick , Kappos Ludwig , Kuhle Jens , Granziera Cristina
Published: August 2024

The detection of contrast-enhancing lesions (CELs) is fundamental for the diagnosis and monitoring of patients with multiple sclerosis (MS). This task is time-consuming and suffers from high intra- and inter-rater variability in clinical practice. However, only a few studies proposed automatic approaches for CEL detection. This study aimed to develop a deep learning model that automatically detects and segments CELs in clinical Magnetic Resonance Imaging (MRI) scans. A 3D UNet-based network was trained with clinical MRI from the Swiss Multiple Sclerosis Cohort. The dataset comprised 372 scans from 280 MS patients: 162 showed at least one CEL, while 118 showed no CELs. The input dataset consisted of T1-weighted before and after gadolinium injection, and FLuid Attenuated Inversion Recovery images. The sampling strategy was based on a white matter lesion mask to confirm the existence of real contrast-enhancing lesions. To overcome the dataset imbalance, a weighted loss function was implemented. The Dice Score Coefficient and True Positive and False Positive Rates were 0.76, 0.93, and 0.02, respectively. Based on these results, the model developed in this study might well be considered for clinical decision support.
Optimizing Production, Characterization, and In Vitro Behavior of Silymarin–Eudragit Electrosprayed Fiber for Anti-Inflammatory Effects: A Chemical Study
Authors: Madiyar Foram , Suskavcevic Liam , Daugherty Kaitlyn , Weldon Alexis , Ghate Sahil , O’Brien Takara , Melendez Isabel , Morgan Karl , Boetcher Sandra , Namilae Lasya
Published: August 2024

Inflammatory Bowel Disease (IBD) is a chronic condition that affects approximately 1.6 million Americans. While current polyphenols for treating IBD can be expensive and cause unwanted side effects, there is an opportunity regarding a new drug/polymer formulation using silymarin and an electrospray procedure. Silymarin is a naturally occurring polyphenolic flavonoid antioxidant that has shown promising results as a pharmacological agent due to its antioxidant and hepatoprotective characteristics. This study aims to produce a drug–polymer complex named the SILS100-Electrofiber complex, using an electrospray system. The vertical set-up of the electrospray system was optimized at a 1:10 of silymarin and Eudragit® S100 polymer to enhance surface area and microfiber encapsulation. The SILS100-Electrofiber complex was evaluated using drug release kinetics via UV Spectrophotometry, Fourier-Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), and Differential Scanning Calorimetry (DSC). Drug loading, apparent solubility, and antioxidant activity were also evaluated. The study was successful in creating fiber-like encapsulation of the silymarin drug with strand diameters ranging from 5–7 μm, with results showing greater silymarin release in Simulated Intestinal Fluid (SIF) compared to Simulated Gastric Fluid (SGF). Moving forward, this study aims to provide future insight into the formulation of drug–polymer complexes for IBD treatment and targeted drug release using electrospray and microencapsulation.
Pathological Role of High Sugar in Mitochondrial Respiratory Chain Defect-Augmented Mitochondrial Stress
Authors: Cham Ebrima D. , Peng Tsung-I , Jou Mei-Jie
Published: August 2024

According to many research groups, high glucose induces the overproduction of superoxide anions, with reactive oxygen species (ROS) generally being considered the link between high glucose levels and the toxicity seen at cellular levels. Respiratory complex anomalies can lead to the production of ROS. Calcium [Ca2+] at physiological levels serves as a second messenger in many physiological functions. Accordingly, mitochondrial calcium [Ca2+]m overload leads to ROS production, which can be lethal to the mitochondria through various mechanisms. F1F0-ATPase (ATP synthase or complex V) is the enzyme responsible for catalyzing the final step of oxidative phosphorylation. This is achieved by F1F0-ATPase coupling the translocation of protons in the mitochondrial intermembrane space and shuttling them to the mitochondrial matrix for ATP synthesis to take place. Mitochondrial complex V T8993G mutation specifically blocks the translocation of protons across the intermembrane space, thereby blocking ATP synthesis and, in turn, leading to Neuropathy, Ataxia, and Retinitis Pigmentosa (NARP) syndrome. This study seeks to explore the possibility of [Ca2+]m overload mediating the pathological roles of high glucose in defective respiratory chain-mediated mitochondrial stress. NARP cybrids are the in vitro experimental models of cells with F1FO-ATPase defects, with these cells harboring 98% of mtDNA T8993G mutations. Their counterparts, 143B osteosarcoma cell lines, are the parental cell lines used for comparison. We observed that NARP cells mediated and enhanced the death of cells (apoptosis) when incubated with hydrogen peroxide (H2O2) and high glucose, as depicted using the MTT assay of cell viability. Furthermore, using fluorescence probe-coupled laser scanning confocal imaging microscopy, NARP cells were found to significantly enable mitochondrial reactive oxygen species (mROS) formation and enhance the depolarization of the mitochondrial membrane potential (ΔΨm). Elucidating the mechanisms of sugar-enhanced toxicity on the mitochondria may, in the future, help to alleviate the symptoms of patients with NARP syndromes and other neurodegenerative diseases.
Effect of Probiotic Fermented Milk Supplementation on Glucose and Lipid Metabolism Parameters and Inflammatory Markers in Patients with Type 2 Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials
Authors: Zhong Hao , Wang Lingmiao , Jia Fuhuai , Yan Yongqiu , Xiong Feifei , Hidayat Khemayanto , Li Yunhong
Published: August 2024

Modulating gut microbiota composition through probiotic administration has been proposed as a novel therapy for type 2 diabetes mellitus (T2DM), and fermented milk is arguably the most common and ideal probiotic carrier. The present meta-analysis was performed to assess the effects of probiotic fermented milk supplementation on glucose and lipid metabolism parameters and inflammatory markers in patients with T2DM using published data from randomized controlled trials (RCTs). The PubMed, Web of Science, and Cochrane Library databases were searched for relevant RCTs. A random-effects model was used to generate the weighted mean difference (WMD) and 95% confidence interval (95% CI). Probiotic fermented milk supplementation reduced the levels of fasting plasma glucose (MD = −17.01, 95% CI −26.43, −7.58 mg/dL; n = 7), hemoglobin A1c (MD = −0.47, 95% CI −0.74, −0.21%; n = 7), total cholesterol (MD = −5.15, 95% CI −9.52, −0.78 mg/dL; n = 7), and C-reactive protein (MD = −0.25, 95% CI −0.43, −0.08; n = 3) but did not significantly affect the levels of HOMA-IR (MD = −0.89, 95% CI −2.55, 0.78; n = 3), triglyceride (MD = −4.69, 95% CI −14.67, 5.30 mg/dL; n = 6), low-density lipoprotein cholesterol (MD = −4.25, 95% CI −8.63, 0.13 mg/dL; n = 7), high-density lipoprotein cholesterol (MD = 1.20, 95% CI −0.96, 3.36 mg/dL; n = 7), and tumor necrosis factor-alpha (MD: −0.58, 95% CI −1.47, 0.32 pg/mL; n = 2). In summary, the present findings provide a crude indication of the potential benefits of probiotic fermented milk supplementation in improving glucose and lipid metabolism and inflammation in patients with T2DM. However, more robust evidence is needed to determine the clinical significance of probiotic fermented milk in the management of T2DM.
Trait Variation and Spatiotemporal Dynamics across Avian Secondary Contact Zones
Authors: Wang Shangyu , Wu Lei , Zhu Qianghui , Wu Jiahao , Tang Shiyu , Zhao Yifang , Cheng Yalin , Zhang Dezhi , Qiao Gexia , Zhang Runzhi , Lei Fumin
Published: August 2024

A secondary contact zone (SCZ) is an area where incipient species or divergent populations may meet, mate, and hybridize. Due to the diverse patterns of interspecific hybridization, SCZs function as field labs for illuminating the on-going evolutionary processes of speciation and the establishment of reproductive isolation. Interspecific hybridization is widely present in avian populations, making them an ideal system for SCZ studies. This review exhaustively summarizes the variations in unique traits within avian SCZs (vocalization, plumage, beak, and migratory traits) and the various movement patterns of SCZs observed in previous publications. It also highlights several potential future research directions in the genomic era, such as the relationship between phenotypic and genomic differentiation in SCZs, the genomic basis of trait differentiation, SCZs shared by multiple species, and accurate predictive models for forecasting future movements under climate change and human disturbances. This review aims to provide a more comprehensive understanding of speciation processes and offers a theoretical foundation for species conservation.
LncRNA495810 Promotes Proliferation and Migration of Hepatocellular Carcinoma Cells by Interacting with FABP5
Authors: Wu Haili , Yuan Haiyan , Duan Yiwei , Li Guangjun , Du Jin’e , Wang Panfeng , Li Zhuoyu
Published: August 2024

Hepatocellular carcinoma (HCC) is one of the malignant tumors with high morbidity and mortality. Long non-coding RNAs (lncRNAs) are frequently dysregulated in human cancers and play an important role in the initiation and progression of HCC. Here, we investigated the expression of a new reported lncRNA495810 in our previous study by analyzing the publicly available datasets and using RT-qPCR assay. The cell proliferation experiment, cell cycle and apoptosis assay, wound healing assay, cell migration assay were used to explore the biological function of lncRNA495810 in HCC. The western blot, RNA pull down and RNA immunoprecipitation (RIP) detection were used to investigate the potential molecular mechanisms of lncRNA495810. The results demonstrated that lncRNA495810 was significantly upregulated in hepatocellular carcinoma and associated with poor prognosis of hepatocellular carcinoma patients. Moreover, it proved that lncRNA495810 promotes the proliferation and metastasis of hepatoma cells by directly binding and upregulating the expression of fatty acid-binding protein 5. These results reveal the oncogenic roles of lncRNA495810 in HCC and provide a potential therapeutic target for HCC.
Effectiveness of Sampling Techniques in Collecting the Polyp Stage of the Invasive Freshwater Hydrozoan Craspedacusta sowerbii
Authors: Zhu Jonathan A. , Folino-Rorem Nadine C.
Published: August 2024

Current sampling methods for detecting the presence of the invasive freshwater hydrozoan Craspedacusta sowerbii rely mainly on visual confirmation of the medusa stage. Confirming the presence of the polyp stage is equally important for observing medusae since typical late summer/early fall occurrences or observations of medusae are sporadic though are becoming more frequent. The polyp stage is important as it is the organism’s primary stage and is present throughout the year depending on water temperatures. Therefore, sampling methods for the polyp stage are, commonly, the collection of substrates such as rocks, plants, or pieces of wood in a given body of water, and these can be cumbersome to examine. Polyps are also small, transparent, and difficult to see on natural substrates. Based on a preliminary culturing of the polyp stage on glass and plastic microscope slides in the laboratory, we designed a sampling methodology based on submerging four substrate types (glass and plastic microscope slides, Hester-Dendy discs, and small glass Petri dishes) to confirm the presence of C. sowerbii polyps in the field. We tested this method in three lakes in the Illinois–Indiana region (USA). Two of the lakes have recorded sightings of medusae but the third has no record of polyps or medusae. The sampling method we designed was effective in that C. sowerbii polyps were found on both plastic and glass slides. While this method can be sufficient for detection of the polyp stage, it also shows potential for improvement; we highlight abiotic and biotic ecological parameters as significant factors influencing the collection of C. sowerbii polyps to be considered for future methodologies.
Exploration of Protease Resources in the Gut of Omnivorous Gryllotalpa orientalis (Orthoptera: Gryllotalpidae)
Authors: Zheng Xiang , Wu Fangtong , Zhao Lu , Zhou He , Zhou Zhijun , Jia Zhenhua , Shi Fuming
Published: August 2024

An insect’s gut microbiome is an essential “organ” in their life cycle, playing a crucial role by aiding food digestion and nutrient absorption. This study employed both culture-independent and culture-dependent methods to explore the protease resources present in the gut of the omnivorous insect Gryllotalpa orientalis. The findings revealed that the gut extract of G. orientalis contained a diverse array of proteases, including cysteine proteases, pepsin, serine proteases, and trypsin, as well as some unidentified proteases. Furthermore, the protease gene htpX, derived from gut bacterium Priestia megaterium DX-3, has been cloned and recombinantly expressed. The recombinant DX-3-htpX protease exhibited a 61.9-fold increase in fermentation level compared to the DX-3 protease. This protease was characterized as a neutral, heat-resistant metalloprotease with an M48 peptidase domain, and it was observed that the binding of Ca2+ to the recombinant protease resulted in the formation of the largest active pocket. This study provides technical support for further development and utilization of functional protein resources in insect gut.
Addition of Mitoquinone (MitoQ) to Fresh Human Sperm Enhances Sperm Motility without Attenuating Viability
Authors: Al-Tarayra Nehad , Al-Alami Zina M. , Battah Abdelkader , Muhaidat Nadia
Published: August 2024

The preparation of human sperm in an andrology laboratory subjects it to oxidative stress. Reactive oxygen species are produced by mitochondria, making it susceptible to oxidative damage; hence, mitochondria-targeted antioxidants like Mitoquinone (MitoQ) might have therapeutic potential for oxidative-damage-associated disorders. The current research aims to establish whether MitoQ has any positive effects during in vitro preparation of fresh human sperm. Viability and motility are evaluated to determine the effective MitoQ concentration and to assess whether MitoQ supplementation is affected by sperm concentration by incubating normospermia semen samples at 37 °C for 2 h and 4 h, respectively. The effect of semen centrifugation following supplementation of 20 × 106 sperm/mL with 200 nM MitoQ is also assessed by measuring viability, motility and sperm DNA fragmentation. The best sperm motility is achieved after 2 h of incubation with 200 nM MitoQ at 37 °C. Sperm concentration of 20 × 106 sperm/mL is the best concentration where 200 nM MitoQ works efficiently. For semen centrifugation at 300× g for 20 min, supplementation with 200 nM MitoQ shows higher sperm motility. The current results demonstrate that MitoQ supplementation during in vitro human semen preparation procedures positively affects fresh sperm motility without affecting viability or increasing DNA fragmentation.
iPhyDSDB: Phytoplasma Disease and Symptom Database
Authors: Wei Wei , Shao Jonathan , Zhao Yan , Inaba Junichi , Ivanauskas Algirdas , Bottner-Parker Kristi D. , Costanzo Stefano , Kim Bo Min , Flowers Kailin , Escobar Jazmin
Published: August 2024

Phytoplasmas are small, intracellular bacteria that infect a vast range of plant species, causing significant economic losses and impacting agriculture and farmers’ livelihoods. Early and rapid diagnosis of phytoplasma infections is crucial for preventing the spread of these diseases, particularly through early symptom recognition in the field by farmers and growers. A symptom database for phytoplasma infections can assist in recognizing the symptoms and enhance early detection and management. In this study, nearly 35,000 phytoplasma sequence entries were retrieved from the NCBI nucleotide database using the keyword “phytoplasma” and information on phytoplasma disease-associated plant hosts and symptoms was gathered. A total of 945 plant species were identified to be associated with phytoplasma infections. Subsequently, links to symptomatic images of these known susceptible plant species were manually curated, and the Phytoplasma Disease Symptom Database (iPhyDSDB) was established and implemented on a web-based interface using the MySQL Server and PHP programming language. One of the key features of iPhyDSDB is the curated collection of links to symptomatic images representing various phytoplasma-infected plant species, allowing users to easily access the original source of the collected images and detailed disease information. Furthermore, images and descriptive definitions of typical symptoms induced by phytoplasmas were included in iPhyDSDB. The newly developed database and web interface, equipped with advanced search functionality, will help farmers, growers, researchers, and educators to efficiently query the database based on specific categories such as plant host and symptom type. This resource will aid the users in comparing, identifying, and diagnosing phytoplasma-related diseases, enhancing the understanding and management of these infections.
Tumor Microenvironment-Responsive Magnetotactic Bacteria-Based Multi-Drug Delivery Platform for MRI-Visualized Tumor Photothermal Chemodynamic Therapy
Authors: Feng Feng , Li Qilong , Sun Xuefei , Yao Li , Wang Xiuyu
Published: August 2024

Cancer cells display elevated reactive oxygen species (ROS) and altered redox status. Herein, based on these characteristics, we present a multi-drug delivery platform, AMB@PDAP-Fe (APPF), from the magnetotactic bacterium AMB-1 and realize MRI-visualized tumor-microenvironment-responsive photothermal–chemodynamic therapy. The Fe3+ in PDAP-Fe is reduced by the GSH at the tumor site and is released in the form of highly active Fe2+, which catalyzes the generation of ROS through the Fenton reaction and inhibits tumor growth. At the same time, the significant absorption of the mineralized magnetosomes in AMB-1 cells in the NIR region enables them to efficiently convert near-infrared light into heat energy for photothermal therapy (PTT), to which PDAP also contributes. The heat generated in the PTT process accelerates the process of Fe2+ release, thereby achieving an enhanced Fenton reaction in the tumor microenvironment. In addition, the magnetosomes in AMB-1 are used as an MRI contrast agent, and the curing process is visualized. This tumor microenvironment-responsive MTB-based multi-drug delivery platform displays the potency to combat tumors and demonstrates the utility and practicality of understanding the cooperative molecular mechanism when designing multi-drug combination therapies.
Morphological Analysis of a New Species of Micropterus (Teleostei: Centrarchidae) from Lake Erie, PA, USA
Authors: Ross Andrew T. , Stauffer Jay R.
Published: August 2024

This previously undescribed species of Micropterus is described from collections in Lake Erie. The species was first recognized by the tri-colored tail of juveniles. This tri-colored tail, the presence of bold parallel lines ventral to the lateral band, and scales in the inter-radial membranes of the dorsal fin distinguish it from Micropterus nigricans. The large mouth that extends past the eye distinguishes it from Micropterus punctulatus.
The Constellation of Risk Factors and Paraneoplastic Syndromes in Cholangiocarcinoma: Integrating the Endocrine Panel Amid Tumour-Related Biology (A Narrative Review)
Authors: Ciobica Mihai-Lucian , Sandulescu Bianca-Andreea , Chicea Liana-Maria , Iordache Mihaela , Groseanu Maria-Laura , Carsote Mara , Nistor Claudiu , Radu Ana-Maria
Published: August 2024

Cholangiocarcinomas (CCAs), a heterogeneous group of challenging malignant tumours which originate from the biliary epithelium, are associated with an alarming increasing incidence during recent decades that varies between different regions of the globe. Thus, awareness represents the key operating factor. Our purpose was to overview the field of CCAs following a double perspective: the constellation of the risk factors, and the presence of the paraneoplastic syndromes, emphasizing the endocrine features amid the entire multidisciplinary panel. This is a narrative review. A PubMed-based search of English-language original articles offered the basis of this comprehensive approach. Multiple risk factors underlying different levels of statistical evidence have been listed such as chronic biliary diseases and liver conditions, inflammatory bowel disease, parasitic infections (e.g., Opisthorchis viverrini, Clonorchis sinensis), lifestyle influence (e.g., alcohol, smoking), environmental exposure (e.g., thorotrast, asbestos), and certain genetic and epigenetic interplays. With regard to the endocrine panel, a heterogeneous spectrum should be taken into consideration: non-alcoholic fatty liver disease, obesity, type 2 diabetes mellitus, and potential connections with vitamin D status, glucagon-like peptide 1 receptor, or the galanin system, respectively, with exposure to sex hormone therapy. Amid the numerous dermatologic, hematologic, renal, and neurologic paraneoplastic manifestations in CCAs, the endocrine panel is less described. Humoral hypercalcaemia of malignancy stands as the most frequent humoral paraneoplastic syndrome in CCAs, despite being exceptional when compared to other paraneoplastic (non-endocrine) manifestations and to its reported frequency in other (non-CCAs) cancers (it accompanies 20–30% of all cancers). It represents a poor prognosis marker in CCA; it may be episodic once the tumour relapses. In addition to the therapy that targets the originating malignancy, hypercalcaemia requires the administration of bisphosphonates (e.g., intravenous zoledronic acid) or denosumab. Early detection firstly helps the general wellbeing of a patient due to a prompt medical control of high serum calcium and it also provides a fine biomarker of disease status in selected cases that harbour the capacity of PTHrP secretion. The exact molecular biology and genetic configuration of CCAs that display such endocrine traits is still an open matter, but humoral hypercalcaemia adds to the overall disease burden.
Plectin: Dual Participation in Tumor Progression
Authors: Wang Zhihui , Wang Wenbin , Luo Qing , Song Guanbin
Published: August 2024

The plectin gene can encode a cytoskeletal linking protein, plectin, known for its interaction with three critical components of the cellular cytoskeleton: intermediate filaments, microtubules, and actin filaments. In recent years, more and more studies have reported that plectin is closely related to tumorigenesis and development, exhibiting both tumor-suppressive and tumor-promoting functions. Here, we first introduce the molecular structure and function of plectin, and then we summarize the current understanding of the crucial role of plectin in cancer progression. Finally, we also discuss the possible reasons for the different roles of plectin expression in various types of cancer and highlight the double-edged sword role of plectin in tumor progression. The review aims to deepen the comprehensive understanding of plectin’s role in cancer and further help to develop novel therapeutic strategies and drug targets.
Evaluation of Endoplasmic Reticulum Stress in an Experimental Intestinal Ischemia–Reperfusion Model in Rats: The Role of Ozone Therapy and Trimetazidine
Authors: Demiral Gokhan , Mercantepe Tolga , Altuntas Gurkan , Pergel Ahmet , Kalcan Suleyman , Ozdemir Ali , Tumkaya Levent , Mataraci Karakas Sibel , Ozturk Aykut , Yilmaz Adnan
Published: August 2024

Aim: The objective of the study was to assess the impact of ozone (O3) and trimetazidine on the intestines following ischemia–reperfusion (I/R) injury through the investigation of endoplasmic reticulum stress. Methods: Forty Sprague Dawley rats were separated into five groups. The groups were named as follows: control, O3, I/R, I/R + trimetazidine (TMZ), and I/R + O3. The control group had laparotomy and exploration of the superior mesenteric artery (SMA) only. Furthermore, alongside laparotomy and SMA exploration, an intraperitoneal (i.p.) administration of a 0.7 mg/kg ozone–oxygen (O3-O2) combination was given to the O3 group. In the experimental groups, the SMA was blocked with the silk suture ligation technique for a duration of 1 h and then restored to normal blood flow for another hour. In the I/R + O3 group, ozone was delivered i.p. at a dosage of 0.7 mg/kg, 30 min after ischemia. In the I/R + TMZ group, a dose of 20 mg/kg/day of trimetazidine was administered orally via gavage for a duration of 7 days, beginning 1 week prior to the induction of ischemia. Intestinal tissues were taken to assess indicators of intestinal mucosal injury and oxidative stress. Results: The level of the lipid peroxidation marker malondialdehyde (MDA) was significantly reduced in the experimental groups as compared to the I/R group (p < 0.05). The experimental groups had considerably greater levels of glutathione (GSH), which reflects antioxidant capacity, compared to the I/R group (p < 0.05). Nevertheless, the concentration of GSH was observed to be increased in the I/R + O3 group in comparison to the I/R + TMZ group (p < 0.05). The histopathological damage score showed a substantial decrease in the experimental groups as compared to the I/R group (p < 0.05). The I/R + O3 group had the lowest injury score. The experimental groups exhibited significantly reduced positivity of the endoplasmic reticulum (ER) stress markers C/EBP homologous protein (CHOP) and glucose-regulated protein (GRP)-78 compared to the I/R group (p < 0.05). Conclusions: The findings provide evidence for the potential advantages of utilizing ozone therapy in the treatment of intestinal ischemia–reperfusion injury. Additionally, they propose that ozone should be assessed in more extensive clinical trials in the future as a therapeutic agent that can disrupt endoplasmic reticulum stress.
The Phenotypes and Functions of Neutrophils in Systemic Sclerosis
Authors: Luo Jiao , Xie Zhongming , Duan Lihua
Published: August 2024

Systemic sclerosis (SSc) is a chronic disease of the connective tissue characterized by its multifaceted impact on various bodily systems, yet its precise cause remains elusive. Central to its pathology are abnormal immune activation, vasculopathy, and consequent fibrosis affecting both the skin and internal organs. The intricate interplay between the innate and adaptive immune systems significantly influences the pathogenesis of SSc. Despite substantial research, the role of neutrophils, key players in innate immunity, in the context of SSc has remained enigmatic. Emerging evidence suggests that neutrophils not only contribute to the initiation and perpetuation of SSc but also inflict damage on organs and promote fibrosis—a hallmark of the disease in many patients. This review aims to investigate the nuanced involvement of neutrophils in the development of SSc. By shedding light on the intricate mechanisms through which neutrophils influence the pathogenesis of SSc, we can gain deeper insights into the disease process and potentially identify novel therapeutic targets. Understanding the precise role of neutrophils may pave the way for more targeted and effective interventions to alleviate the burden of SSc on affected individuals.
Oxidative Stress and Cataract Formation: Evaluating the Efficacy of Antioxidant Therapies
Authors: Kulbay Merve , Wu Kevin Y. , Nirwal Gurleen K. , Bélanger Paul , Tran Simon D.
Published: August 2024

This comprehensive review investigates the pivotal role of reactive oxygen species (ROS) in cataract formation and evaluates the potential of antioxidant therapies in mitigating this ocular condition. By elucidating the mechanisms of oxidative stress, the article examines how ROS contribute to the deterioration of lens proteins and lipids, leading to the characteristic aggregation, cross-linking, and light scattering observed in cataracts. The review provides a thorough assessment of various antioxidant strategies aimed at preventing and managing cataracts, such as dietary antioxidants (i.e., vitamins C and E, lutein, and zeaxanthin), as well as pharmacological agents with antioxidative properties. Furthermore, the article explores innovative therapeutic approaches, including gene therapy and nanotechnology-based delivery systems, designed to bolster antioxidant defenses in ocular tissues. Concluding with a critical analysis of current research, the review offers evidence-based recommendations for optimizing antioxidant therapies. The current literature on the use of antioxidant therapies to prevent cataract formation is sparse. There is a lack of evidence-based conclusions; further clinical studies are needed to endorse the use of antioxidant strategies in patients to prevent cataractogenesis. However, personalized treatment plans considering individual patient factors and disease stages can be applied. This article serves as a valuable resource, providing insights into the potential of antioxidants to alleviate the burden of cataracts.
Matrix Metalloproteinases in Health and Disease 3.0
Authors: Serra Raffaele
Published: August 2024

Matrix metalloproteinases (MMPs) are members of an enzyme family that are critical for maintaining tissue allostasis [...]
Insight into the Association between Slitrk Protein and Neurodevelopmental and Neuropsychiatric Conditions
Authors: Puranik Nidhi , Song Minseok
Published: August 2024

Slitrk proteins belong the leucine-rich repeat transmembrane family and share structural similarities with the Slits and tropomyosin receptor kinase families, which regulate the development of the nervous system. Slitrks are highly expressed in the developing nervous system of vertebrates, modulating neurite outgrowth and enhancing synaptogenesis; however, the expression and function of Slitrk protein members differ. Slitrk protein variations have been associated with various sensory and neuropsychiatric conditions, including myopia, deafness, obsessive–compulsive disorder, autism spectrum disorders, schizophrenia, attention-deficit/hyperactivity disorder, glioma, and Tourette syndrome; however, the underlying mechanism remains unclear. Therefore, the Slitrk family members’ protein expression, roles in the signaling cascade, functions, and gene mutations need to be comprehensively studied to develop therapeutics against neurodegenerative diseases. This study presents complete and pertinent information demonstrating the relationship between Slitrk family proteins and neuropsychiatric illnesses. This review briefly discusses neurodevelopmental disorders, the leucine-rich repeat family, the Slitrk family, and the association of Slitrk with the neuropathology of representative disorders.
Membrane Activity and Viroporin Assembly for the SARS-CoV-2 E Protein Are Regulated by Cholesterol
Authors: Volovik Marta V. , Denieva Zaret G. , Gifer Polina K. , Rakitina Maria A. , Batishchev Oleg V.
Published: August 2024

The SARS-CoV-2 E protein is an enigmatic viral structural protein with reported viroporin activity associated with the acute respiratory symptoms of COVID-19, as well as the ability to deform cell membranes for viral budding. Like many viroporins, the E protein is thought to oligomerize with a well-defined stoichiometry. However, attempts to determine the structure of the protein complex have yielded inconclusive results, suggesting several possible oligomers, ranging from dimers to pentamers. Here, we combined patch-clamp, confocal fluorescence microscopy on giant unilamellar vesicles, and atomic force microscopy to show that E protein can exhibit two modes of membrane activity depending on membrane lipid composition. In the absence or the presence of a low content of cholesterol, the protein forms short-living transient pores, which are seen as semi-transmembrane defects in a membrane by atomic force microscopy. Approximately 30 mol% cholesterol is a threshold for the transition to the second mode of conductance, which could be a stable pentameric channel penetrating the entire lipid bilayer. Therefore, the E-protein has at least two different types of activity on membrane permeabilization, which are regulated by the amount of cholesterol in the membrane lipid composition and could be associated with different types of protein oligomers.
Zebrafish Suppressor of Cytokine Signaling 4b (Socs4b) Is Dispensable for Development but May Regulate Epidermal Growth Factor Receptor Signaling
Authors: Trengove Monique , Rasighaemi Parisa , Liongue Clifford , Ward Alister C.
Published: August 2024

The suppressor of cytokine signaling (SOCS) family of proteins were named after their defining role as negative feedback regulators of signaling initiated by numerous cytokine receptors. However, multiple members of the SOCS family likely function outside of this paradigm, including SOCS4. Zebrafish possess two SOCS4 paralogues, with socs4a previously shown to participate in central nervous system development and function. This study examined the role of the other paralogue, socs4b, through expression analysis and functional investigations in vivo and in vitro. This revealed maternal deposition of socs4b mRNA, specific zygotic expression during late embryogenesis, including in the brain, eye and intestine, and broad adult expression that was highest in the brain. A mutant allele, socs4bΔ18, was generated by genome editing, in which the start codon was deleted. Fish homozygous for this likely hypomorphic allele showed no overt developmental phenotypes. However, in vitro studies suggested the Socs4b protein may be able to regulate EGFR signaling.
The Current Role of Collagen Patch Augmentation in Rotator Cuff Pathology: A Narrative Review
Authors: Wee Wen Hon Darren , Tan Zhi Wei Nicholas Matthias , Quek Clara X. , Yik Jing Hui , Ho Sean Wei Loong
Published: August 2024

Rotator cuff repair is a common orthopaedic procedure. Despite advancements in the mechanics of rotator cuff repair, the re-tear rate post repair remains significant. This review assesses the available literature on usage of collagen bio-inductive scaffolds for rotator cuff repairs. Augmentation of biology is a key strategy to improving success of rotator cuff repair. Current evidence suggests that augmentation of rotator cuff repairs with a collagen bio-inductive scaffold improves the thickness of the rotator cuff. There is a favourable safety profile, and its usage may improve re-tear rates. However, there is currently no consensus on whether clinical outcomes are improved by the usage of collagen bio-inductive scaffolds. Further research is necessary to increase our understanding of the clinical effects of using collagen bio-inductive scaffolds and to determine which patient profiles will best benefit from its usage.
Hydrogen Sulfide Modulation of Matrix Metalloproteinases and CD147/EMMPRIN: Mechanistic Pathways and Impact on Atherosclerosis Progression
Authors: Munteanu Constantin , Galaction Anca Irina , Poștaru Mădălina , Rotariu Mariana , Turnea Marius , Blendea Corneliu Dan
Published: August 2024

Atherosclerosis is a chronic inflammatory condition marked by endothelial dysfunction, lipid accumulation, inflammatory cell infiltration, and extracellular matrix (ECM) remodeling within arterial walls, leading to plaque formation and potential cardiovascular events. Key players in ECM remodeling and inflammation are matrix metalloproteinases (MMPs) and CD147/EMMPRIN, a cell surface glycoprotein expressed on endothelial cells, vascular smooth muscle cells (VSMCs), and immune cells, that regulates MMP activity. Hydrogen sulfide (H₂S), a gaseous signaling molecule, has emerged as a significant modulator of these processes including oxidative stress mitigation, inflammation reduction, and vascular remodeling. This systematic review investigates the mechanistic pathways through which H₂S influences MMPs and CD147/EMMPRIN and assesses its impact on atherosclerosis progression. A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science databases, focusing on studies examining H₂S modulation of MMPs and CD147/EMMPRIN in atherosclerosis contexts. Findings indicate that H₂S modulates MMP expression and activity through transcriptional regulation and post-translational modifications, including S-sulfhydration. By mitigating oxidative stress, H₂S reduces MMP activation, contributing to plaque stability and vascular remodeling. H₂S also downregulates CD147/EMMPRIN expression via transcriptional pathways, diminishing inflammatory responses and vascular cellular proliferation within plaques. The dual regulatory role of H₂S in inhibiting MMP activity and downregulating CD147 suggests its potential as a therapeutic agent in stabilizing atherosclerotic plaques and mitigating inflammation. Further research is warranted to elucidate the precise molecular mechanisms and to explore H₂S-based therapies for clinical application in atherosclerosis.
Design and Performance Analysis of Robotic Vertebral-Disc Unit with Cable-Driven Mechanism
Authors: Gao Wenshuo , Tian Zhiwei , Duan Famin , Han Chunxiao
Published: August 2024

The humanoid torso is crucial for the overall performance of a humanoid robot. Developing an effective humanoid spine is essential for enhancing this mechanism. This paper introduces a one-vertebral-disc unit inspired by human spine anatomy. A prototype was created using 3D-printed parts and commercially available components. Two general human-like motions are achieved using two servo motors and two pulleys, reducing the number of servo motors needed. The results indicate that a one-vertebral-disc unit can bend up to 15 degrees. The proposed mechanism functions effectively and successfully mimics human movements. It holds potential for integration into humanoid torsos, enabling efficient performance in human-like tasks in the future.
Enhancing Heavy Metal Detection through Electrochemical Polishing of Carbon Electrodes
Authors: Billa Sanjeev , Boddu Rohit , Siddiqui Shabnam , Arumugam Prabhu U.
Published: August 2024

Our research addresses the pressing need for environmental sensors capable of large-scale, on-site detection of a wide array of heavy metals with highly accurate sensor metrics. We present a novel approach using electrochemically polished (ECP) carbon screen-printed electrodes (cSPEs) for high-sensitivity detection of cadmium and lead. By applying a range of techniques, including scanning electron microscopy, energy-dispersive spectroscopy, Raman spectroscopy, electrochemical impedance spectroscopy, and cyclic voltammetry, we investigated the impact of the electrochemical potential scan range, scan rate, and the number of cycles on electrode response and its ability to detect cadmium and lead. Our findings reveal a 41 ± 1.2% increase in voltammogram currents and a 51 ± 1.6% decrease in potential separations (n = 3), indicating a significantly improved active electrode area and kinetics. The impedance model elucidates the microstructural and electrochemical property changes in the ECP-treated electrodes, showing an 88 ± 2% (n = 3) decrease in the charge transfer resistance, leading to enhanced electrode electrical conductivity. A bismuth-reduced graphene oxide nanocomposite-modified, ECP-treated electrode demonstrated a higher cadmium and lead sensitivity of up to 5 ± 0.1 μAppb−1cm−2 and 2.7 ± 0.1 μAppb−1cm−2 (n = 3), respectively, resulting in sub-ppb limits of detection in spiked deionized water samples. Our study underscores the potential of optimally ECP-activated electrodes as a foundation for designing ultrasensitive heavy metal sensors for a wide range of real-world heavy metal-contaminated waters.
Microscale Humidity Sensor Based on Iron-Coated Elaters of Equisetum Spores
Authors: Liu Yanting , Lin Zhexuan , Li Xiaochun , Huang Rui , Wu Xuewan , Deng Ruyi , Yuan Kaisong
Published: August 2024

Humidity sensors deeply influence human manufacturing production and daily life, while researchers generally focus on developing humidity sensors with higher stability, higher linearity, rapid response time, etc. Yet, few people discuss measuring humidity in the microenvironment by miniaturizing sensor size into a microscale, in which the existing humidity sensors are difficult to reach. Accordingly, this study proposes a methodology for measuring relative humidity in the microscale by utilizing the distinctive morphologies of Equisetum spores across a range of relative humidities between 50% and 90%. Equisetum spores are responsive to changes in ambient relative humidity and remain in their original activities even after iron sputtering, which aims to endow the sensor with magnetic properties. The test performed in this study demonstrated a response time of 3.3 s and a recovery time of 3.6 s. In the first application, we employed such microscale sensors to work in the channel of the microfluidic chip or the cell migration microchip, as an example of working in the microenvironment. COMSOL Multiphysics 6.2 software was also used to simulate the change in relative humidity in such microchannels. Secondly, such microscale sensors are combined with smartphone-based microscopy to measure the humidity of the skin. These microscale sensors pave the new way to sensing humidity in microenvironments.
Free Flight Training as a Tool for Psittacine Reintroductions
Authors: Brightsmith Donald J. , Biro Chris , Mendes Humberto F. , Woodman Constance
Published: August 2024

As habitat loss and other threats accelerate, ecological restoration and reintroduction science are becoming progressively more important. The psittacines are among the most endangered bird groups and are prime candidates for restoration through reintroduction. Unfortunately, post-release survival of captive-raised animals is often quite low because, in part, of high predation rates, low site fidelity, poor flight ability, and low flock cohesion. Current best practices in parrot release hold the birds in captivity for a year or more and include distinct methods to address each of these challenges. Here, we conduct a small-scale, proof-of-concept study using free flight methods and human-socialized trained adult birds to hand raise and release a group of six fledgling Blue-and-yellow Macaws in their historical range in southeastern Brazil. All six released birds showed strong flock cohesion and fidelity to the release site, avoided predation, and survived without supplemental feeding for over one year. One bird was captured by local people but was recovered and rereleased and it has reintegrated into the group and is still alive and doing well. The human-socialized trained adult birds modeled both desirable behaviors (flocking, foraging, reacting to predators) and undesirable behaviors and they were returned to captivity before the conclusion of this study. Our study suggests that free flight training has great potential to help captive-raised young attain a broad array of vital skills needed for survival post-release.
Decline in Sensory Integration in Old Age and Its Related Functional Brain Connectivity Correlates Observed during a Virtual Reality Task
Authors: Inagaki Satoru , Matsuura Hirokazu , Sakurai Kazuki , Minati Ludovico , Yoshimura Natsue
Published: August 2024

Sensory integration is an essential human function whose decline impacts quality of life, particularly in older adults. Herein, we propose an arm-reaching task based on a virtual reality head-mounted display system to assess sensory integration in daily life, and we examined whether reaching task performance was associated with resting-state functional connectivity (rsFC) between the brain regions involved in sensory integration. We hypothesized that declining sensory integration would affect performance during a reaching task with multiple cognitive loads. Using a task in which a young/middle-aged group showed only small individual differences, older adults showed large individual differences in the gap angle between the reaching hand and the target position, which was used to assess sensory integration function. Additionally, rsfMRI data were used to identify correlations between rsFC and performance in older adults, showing that performance was correlated with connectivity between the primary motor area and the left inferior temporal gyrus and temporo-occipital region. Connectivity between areas is related to visuomotor integration; thus, the results suggest the involvement of visuomotor integration in the decline of sensory integration function and the validity of the gap angle during this VR reaching task as an index of functional decline.
Effects of Electroencephalogram Neurofeedback Intervention on Blood C-Reactive Protein Levels in Astronauts Attending 2-Week Long Analog Moon Mission
Authors: Hinca Jakub , Dornowski Marcin
Published: August 2024

The human organism is affected by multiple stressors every single day, especially during extremely demanding activities. It needs a method to regulate itself better. One of the stressors that is affecting humans is social isolation. The state of prolonged isolation happens during space missions. In this study, 40 analog astronauts attended a two-week-long mission. The experimental group had EEG neurofeedback training intervention performed on a daily basis, while the control group remained isolated without neurofeedback. The results let us take this non-invasive intervention under consideration, while debating the methods to lower the physiological stress reaction in humans that are exposed to extremely hard circumstances. Although not statistically significant, the trends observed give us direction towards other research to confirm EEG neurofeedback as a method to lower cell stress response levels.
Influence of Epilepsy Characteristics on the Anxiety Occurrence
Authors: Gavrilovic Aleksandar , Gavrilovic Jagoda , Ilic Zivojinovic Jelena , Jeličić Ljiljana , Radovanovic Snezana , Vesic Katarina
Published: August 2024

The presence of anxiety in individuals with epilepsy significantly influences their medical treatment and quality of life and often goes unrecognized or untreated, posing a challenge to differential diagnosis. The study aimed to investigate the influence of epilepsy characteristics on anxiety. The research involved 155 patients with generalized and focal drug-sensitive [DSE] and drug-resistant [DRE] epilepsy. Hamilton anxiety rating scale [HAS] was used to assess the symptoms of anxiety at three time points [baseline, 12, and 18 months]. DSE patients exhibited significantly lower HAM-A scores than patients with DRE at the initial visit [p = 0.000] after 12 [p = 0.000] and 18-month follow-up [p = 0.000]. Focal DRE patients presented higher HAM-A scores than focal DSE patients in the initial visit [p = 0.000] after 12 [p = 0.000] and 18 months [p = 0.000]. Medication responsiveness, seizure type, and illness duration emerged as significant anxiety predictors [p = 0.000]. After 18 months of follow-up, significant contributors to anxiety were drug responsivity and illness duration [p = 0.000]. The occurrence of anxiety in epilepsy patients is most significantly influenced by well-controlled epilepsy and a positive response to medication.