bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Chorionic Gonadotropin and Early Embryogenesis: Review
Authors: d’Hauterive Sophie Perrier , Close Romann , Gridelet Virginie , Mawet Marie , Nisolle Michelle , Geenen Vincent
Published: January 2022

Human chorionic gonadotropin (hCG) has four major isoforms: classical hCG, hyperglycosylated hCG, free β subunit, and sulphated hCG. Classical hCG is the first molecule synthesized by the embryo. Its RNA is transcribed as early as the eight-cell stage and the blastocyst produces the protein before its implantation. This review synthetizes everything currently known on this multi-effect hormone: hCG levels, angiogenetic activity, immunological actions, and effects on miscarriages and thyroid function.
Photothermal Effect and Multi-Modality Imaging of Up-Conversion Nanomaterial Doped with Gold Nanoparticles
Authors: Zhang Wei , Zang Yang , Lu Yanli , Han Jinhui , Xiong Qingyun , Xiong Jinping
Published: January 2022

Two key concerns exist in contemporary cancer chemotherapy in clinics: limited therapeutic efficiency and substantial side effects in patients. In recent years, researchers have been investigating revolutionary cancer treatment techniques and photo-thermal therapy (PTT) has been proposed by many scholars. A drug for photothermal cancer treatment was synthesized using the hydrothermal method, which has a high light-to-heat conversion efficiency. It may also be utilized as a clear multi-modality bioimaging platform for photoacoustic imaging (PAI), computed tomography (CT), and magnetic resonance imaging (MRI). When compared to single-modality imaging, multi-modality imaging delivers far more thorough and precise details for cancer diagnosis. Furthermore, gold-doped upconverting nanoparticles (UCNPs) have an exceptionally high target recognition for tumor cells. The gold-doped UCNPs, in particular, are non-toxic to normal tissues, endowing the as-prepared medications with outstanding therapeutic efficacy but exceptionally low side effects. These findings may encourage the creation of fresh effective imaging-guided approaches to meet the goal of photothermal cancer therapy.
10-Dehydrogingerdione Attenuates Tramadol-Induced Nephrotoxicity by Modulating Renal Oxidative Stress, Inflammation and Apoptosis in Experimental Rats: Role of HO-1 Activation and TLR4/NF-κB/ERK Inhibition
Authors: Elnagar Gehad M. , Elseweidy Mohamed M. , Mahmoud Yasmin K. , Elkomy Nesreen M. I. M. , Althafar Ziyad M. , Alnomasy Sultan F. , Al-Gabri Naif A. , Shawky Mohamed
Published: January 2022

Tramadol represents a synthetic opioid analgesic especially for mild to severe pain. Its dose must be commonly monitored according to pain status and to alleviate the appearance of any adverse effects such as renal cellular damage during its excretion. Present work aimed mainly to study the effects of tramadol intake on renal tissues and 10-dehydrogingerdione (10-DHGD) potential as a protective agent. Tramadol administration induced an increase in serum levels of urea, creatinine, uric acid, the renal immune expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and caspase-3 which turned out to be decreased by 10-DHGD intake. Our results also recorded a significant increase in renal malondialdehyde (MDA), toll-like receptor 4 (TLR4), and extracellular signal-regulated protein kinase-1 (ERK1) along with glutathione (GSH), superoxide dismutase (SOD), and heme oxygenase-1 (HO-1) decrease due to tramadol intake, which were counteracted by 10-DHGD administration as illustrated and supported by the histopathological findings. Our conclusion refers to renoprotective potential of 10-DHGD against tramadol adverse effects.
Enhanced Ca2+ Entry Sustains the Activation of Akt in Glucose Deprived SH-SY5Y Cells
Authors: Kourti Maria , Liaropoulou Danai , Paschou Maria , Giagklisi Ioanna , Paschalidi Maria , Petani Evangelia , Papazafiri Panagiota
Published: January 2022

The two crucial cellular insults that take place during cerebral ischemia are the loss of oxygen and loss of glucose, which can both activate a cascade of events leading to neuronal death. In addition, the toxic overactivation of neuronal excitatory receptors, leading to Ca2+ overload, may contribute to ischemic neuronal injury. Brain ischemia can be simulated in vitro by oxygen/glucose deprivation, which can be reversible by the re-establishment of physiological conditions. Accordingly, we examined the effects of glucose deprivation on the PI3K/Akt survival signaling pathway and its crosstalk with HIF-1α and Ca2+ homeostasis in SH-SY5Y human neuroblastoma cells. It was found that glucose withdrawal decreased HIF-1α protein levels even in the presence of the ischemia-mimicking CoCl2. On the contrary, and despite neuronal death, we identified a strong activation of the master pro-survival kinase Akt, a finding that was also confirmed by the increased phosphorylation of GSK3, a direct target of p-Akt. Remarkably, the elevated Ca2+ influx recorded was found to promptly trigger the activation of Akt, while a re-addition of glucose resulted in rapid restoration of both Ca2+ entry and p-Akt levels, highlighting the plasticity of neurons to respond to ischemic challenges and the important role of glucose homeostasis for multiple neurological disorders.
Hydrogen Sulfide-Linked Persulfidation Maintains Protein Stability of ABSCISIC ACID-INSENSITIVE 4 and Delays Seed Germination
Authors: Zhou Mingjian , Zhang Jing , Zhou Heng , Zhao Didi , Duan Tianqi , Wang Shuhan , Yuan Xingxing , Xie Yanjie
Published: January 2022

Hydrogen sulfide (H2S) is an endogenous gaseous molecule that plays an important role in the plant life cycle. The multiple transcription factor ABSCISIC ACID INSENSITIVE 4 (ABI4) was precisely regulated to participate in the abscisic acid (ABA) mediated signaling cascade. However, the molecular mechanisms of how H2S regulates ABI4 protein level to control seed germination and seedling growth have remained elusive. In this study, we demonstrated that ABI4 controls the expression of L-CYSTEINE DESULFHYDRASE1 (DES1), a critical endogenous H2S-producing enzyme, and both ABI4 and DES1-produced H2S have inhibitory effects on seed germination. Furthermore, the ABI4 level decreased during seed germination while H2S triggered the enhancement of the persulfidation level of ABI4 and alleviated its degradation rate, which in turn inhibited seed germination and seedling establishment. Conversely, the mutation of ABI4 at Cys250 decreased ABI4 protein stability and facilitated seed germination. Moreover, ABI4 degradation is also regulated via the 26S proteasome pathway. Taken together, these findings suggest a molecular link between DES1 and ABI4 through the post-translational modifications of persulfidation during early seedling development.
Amphiphilic Pentablock Copolymers Prepared from Pluronic and ε-Caprolactone by Enzymatic Ring Opening Polymerization
Authors: El-Fattah Ahmed Abd , Grillo Fernandes Elizabeth , Chiellini Federica , Chiellini Emo
Published: January 2022

Amphiphilic copolymers are appealing materials because of their interesting architecture and tunable properties. In view of their application in the biomedical field, the preparation of these materials should avoid the use of toxic compounds as catalysts. Therefore, enzymatic catalysis is a suitable alternative to common synthetic routes. Pentablock copolymers (CUC) were synthesized with high yields by ring-opening polymerization of ε-caprolactone (ε-CL) initiated by Pluronic (EPE) and catalyzed by Candida antarctica lipase B enzyme. The variables to study the structure–property relationship were EPEs’ molecular weight and molar ratios between ε-CL monomer and EPE macro-initiator (M/In). The obtained copolymers were chemically characterized, the molecular weight determined, and morphologies evaluated. The results suggest an interaction between the reaction time and M/In variables. There was a correlation between the differential scanning calorimetry data with those of X-ray diffraction (WAXD). The length of the central block of CUC copolymers may have an important role in the crystal formation. WAXD analyses indicated that a micro-phase separation takes place in all the prepared copolymers. Preliminary cytotoxicity experiments on the extracts of the polymer confirmed that these materials are nontoxic.
Transcriptomics and Functional Analysis of Copper Stress Response in the Sulfate-Reducing Bacterium Desulfovibrio alaskensis G20
Authors: Tripathi Abhilash Kumar , Saxena Priya , Thakur Payal , Rauniyar Shailabh , Samanta Dipayan , Gopalakrishnan Vinoj , Singh Ram Nageena , Sani Rajesh Kumar
Published: January 2022

Copper (Cu) is an essential micronutrient required as a co-factor in the catalytic center of many enzymes. However, excess Cu can generate pleiotropic effects in the microbial cell. In addition, leaching of Cu from pipelines results in elevated Cu concentration in the environment, which is of public health concern. Sulfate-reducing bacteria (SRB) have been demonstrated to grow in toxic levels of Cu. However, reports on Cu toxicity towards SRB have primarily focused on the degree of toxicity and subsequent elimination. Here, Cu(II) stress-related effects on a model SRB, Desulfovibrio alaskensis G20, is reported. Cu(II) stress effects were assessed as alterations in the transcriptome through RNA-Seq at varying Cu(II) concentrations (5 µM and 15 µM). In the pairwise comparison of control vs. 5 µM Cu(II), 61.43% of genes were downregulated, and 38.57% were upregulated. In control vs. 15 µM Cu(II), 49.51% of genes were downregulated, and 50.5% were upregulated. The results indicated that the expression of inorganic ion transporters and translation machinery was massively modulated. Moreover, changes in the expression of critical biological processes such as DNA transcription and signal transduction were observed at high Cu(II) concentrations. These results will help us better understand the Cu(II) stress-response mechanism and provide avenues for future research.
Effects of Pubertal Exposure to Butyl Benzyl Phthalate, Perfluorooctanoic Acid, and Zeranol on Mammary Gland Development and Tumorigenesis in Rats
Authors: Su Yanrong , Santucci-Pereira Julia , Dang Nhi M. , Kanefsky Joice , Rahulkannan Vishnuprabha , Hillegass Meardey , Joshi Shalina , Gurdogan Hafsa , Chen Zhen , Bessonneau Vincent , Rudel Ruthann , Ser-Dolansky Jennifer , Schneider Sallie S. , Russo Jose
Published: January 2022

Endocrine-disrupting chemicals (EDCs)—including butyl benzyl phthalate (BBP), perfluorooctanoic acid (PFOA), and zeranol (α-ZAL, referred to as ZAL hereafter)—can interfere with the endocrine system and produce adverse effects. It remains unclear whether pubertal exposure to low doses of BBP, PFOA, and ZAL has an impact on breast development and tumorigenesis. We exposed female Sprague Dawley rats to BBP, PFOA, or ZAL through gavage for 21 days, starting on day 21, and analyzed their endocrine organs, serum hormones, mammary glands, and transcriptomic profiles of the mammary glands at days 50 and 100. We also conducted a tumorigenesis study for rats treated with PFOA and ZAL using a 7,12-dimethylbenz[a]anthracene (DMBA) model. Our results demonstrated that pubertal exposure to BBP, PFOA, and ZAL affected endocrine organs and serum hormones, and induced phenotypic and transcriptomic changes. The exposure to PFOA + ZAL induced the most phenotypic and transcriptomic changes in the mammary gland. PFOA + ZAL downregulated the expression of genes related to development at day 50, whereas it upregulated genes associated with tumorigenesis at day 100. PFOA + ZAL exposure also decreased rat mammary tumor latency, reduced the overall survival of rats after DMBA challenge, and affected the histopathology of mammary tumors. Therefore, our study suggests that exposure to low doses of EDCs during the pubertal period could induce changes in the endocrine system and mammary gland development in rats. The inhibition of mammary gland development by PFOA + ZAL might increase the risk of developing mammary tumors through activation of signaling pathways associated with tumorigenesis.
The Multifunctional Faces of T-Cell Intracellular Antigen 1 in Health and Disease
Authors: Fernández-Gómez Andrea , Izquierdo José M.
Published: January 2022

T-cell intracellular antigen 1 (TIA1) is an RNA-binding protein that is expressed in many tissues and in the vast majority of species, although it was first discovered as a component of human cytotoxic T lymphocytes. TIA1 has a dual localization in the nucleus and cytoplasm, where it plays an important role as a regulator of gene-expression flux. As a multifunctional master modulator, TIA1 controls biological processes relevant to the physiological functioning of the organism and the development and/or progression of several human pathologies. This review summarizes our current knowledge of the molecular aspects and cellular processes involving TIA1, with relevance for human pathophysiology.
An Overview on Single-Cell Technology for Hepatocellular Carcinoma Diagnosis
Authors: Aliya Sheik , Lee Hoomin , Alhammadi Munirah , Umapathi Reddicherla , Huh Yun
Published: January 2022

Hepatocellular carcinoma is a primary liver cancer caused by the accumulation of genetic mutation patterns associated with epidemiological conditions. This lethal malignancy exhibits tumor heterogeneity, which is considered as one of the main reasons for drug resistance development and failure of clinical trials. Recently, single-cell technology (SCT), a new advanced sequencing technique that analyzes every single cell in a tumor tissue specimen, aids complete insight into the genetic heterogeneity of cancer. This helps in identifying and assessing rare cell populations by analyzing the difference in gene expression pattern between individual cells of single biopsy tissue which normally cannot be identified from pooled cell gene expression pattern (traditional sequencing technique). Thus, SCT improves the clinical diagnosis, treatment, and prognosis of hepatocellular carcinoma as the limitations of other techniques impede this cancer research progression. Application of SCT at the genomic, transcriptomic, and epigenomic levels to promote individualized hepatocellular carcinoma diagnosis and therapy. The current review has been divided into ten sections. Herein we deliberated on the SCT, hepatocellular carcinoma diagnosis, tumor microenvironment analysis, single-cell genomic sequencing, single-cell transcriptomics, single-cell omics sequencing for biomarker development, identification of hepatocellular carcinoma origination and evolution, limitations, challenges, conclusions, and future perspectives.
Genome-Wide Identification and Characterization of RNA/DNA Differences Associated with Drought Response in Wheat
Authors: Pan Yan , Li Mengqi , Huang Jiaqian , Pan Wenqiu , Shi Tingrui , Guo Qifan , Yang Guang , Nie Xiaojun
Published: January 2022

RNA/DNA difference (RDD) is a post-transcriptional RNA modification to enrich genetic information, widely involved in regulating diverse biological processes in eukaryotes. RDDs in the wheat nuclear genome, especially those associated with drought response or tolerance, were not well studied up to now. In this study, we investigated the RDDs related to drought response based on the RNA-seq data of drought-stressed and control samples in wheat. In total, 21,782 unique RDDs were identified, of which 265 were found to be drought-induced, representing the first drought-responsive RDD landscape in the wheat nuclear genome. The drought-responsive RDDs were located in 69 genes, of which 35 were differentially expressed under drought stress. Furthermore, the effects of RNA/DNA differences were investigated, showing that they could result in changes of RNA secondary structure, miRNA-target binding as well as protein conserved domains in the RDD-containing genes. In particular, the A to C mutation in TraesCS2A02G053100 (orthology to OsRLCK) led to the loss of tae-miR9657b-5p targeting, indicating that RNA/DNA difference might mediate miRNA to regulate the drought-response process. This study reported the first drought-responsive RDDs in the wheat nuclear genome. It sheds light on the roles of RDD in drought tolerance, and may also contribute to wheat genetic improvement based on epi-transcriptome methods.
Regulation of Opsin Gene Expression by DNA Methylation and Histone Acetylation
Authors: Song Jin , VanBuskirk Julia A. , Merbs Shannath L.
Published: January 2022

One important role of epigenetic regulation is controlling gene expression in development and homeostasis. However, little is known about epigenetics’ role in regulating opsin expression. Cell cultures (HEK 293, Y79, and WERI) producing different levels of opsins were treated with 5-aza-2’-deoxycytidine (5-Aza-dc) and/or sodium butyrate (SB) or suberoylanilide hydroxamic acid (SAHA) for 72 h. Global DNA methylation, site-specific methylation, and expressions of opsins were measured by LUMA assay, bisulfite pyrosequencing, and qPCR, respectively. Mouse retinal explants from wild-type P0/P1 pups were ex vivo cultured with/without 5-Aza-dc or SAHA for 6 days. The morphology of explants, DNA methylation, and expressions of opsins was examined. The drugs induced global DNA hypomethylation or increased histone acetylation in cells, including DNA hypomethylation of rhodopsin (RHO) and L-opsin (OPN1LW) and a concomitant increase in their expression. Further upregulation of RHO and/or OPN1LW in HEK 293 or WERI cells was observed with 5-Aza-dc and either SB or SAHA combination treatment. Mouse retinal explants developed normally but had drug-dependent differential DNA methylation and expression patterns of opsins. DNA methylation and histone acetylation directly regulate opsin expression both in vitro and ex vivo. The ability to manipulate opsin expression using epigenetic modifiers enables further study into the role of epigenetics in eye development and disease.
Expression Characterization of AtPDI11 and Functional Analysis of AtPDI11 D Domain in Oxidative Protein Folding
Authors: Fan Fenggui , Zhang Hao , Wei Qian , Wei Yahui
Published: January 2022

The formation and isomerization of disulfide bonds mediated by protein disulfide isomerase (PDI) in the endoplasmic reticulum (ER) is of fundamental importance in eukaryotes. Canonical PDI structure comprises four domains with the order of a-b-b′-a′. In Arabidopsis thaliana, the PDI-S subgroup contains only one member, AtPDI11, with an a-a′-D organization, which has no orthologs in mammals or yeast. However, the expression pattern of AtPDI11 and the functioning mechanism of AtPDI11 D domain are currently unclear. In this work, we found that PDI-S is evolutionarily conserved between land plants and algal organisms. AtPDI11 is expressed in various tissues and its induction by ER stress is disrupted in bzip28/60 and ire1a/b mutants that are null mutants of key components in the unfolded protein response (UPR) signal transduction pathway, suggesting that the induction of AtPDI11 by ER stress is mediated by the UPR signaling pathway. Furthermore, enzymatic activity assays and genetic evidence showed that the D domain is crucially important for the activities of AtPDI11. Overall, this work will help to further understand the working mechanism of AtPDI11 in catalyzing disulfide formation in plants.
Rno_circ_0001004 Acts as a miR-709 Molecular Sponge to Regulate the Growth Hormone Synthesis and Cell Proliferation
Authors: Xiong Jiali , Zhang Haojie , Wang Yuxuan , Cheng Yunyun , Luo Junyi , Chen Ting , Xi Qianyun , Sun Jiajie , Zhang Yongliang
Published: January 2022

(1) Background: As a novel type of non-coding RNA with a stable closed-loop structure, circular RNA (circRNA) can interact with microRNA (miRNA) and influence the expression of miRNA target genes. However, circRNA involved in pituitary growth hormone (GH) regulation is poorly understood. Our previous study revealed protein kinase C alpha (PRKCA) as the target gene of miR-709. Currently, the expression and function of rno_circRNA_0001004 in the rat pituitary gland is not clarified; (2) Methods: In this study, both bioinformatics analysis and dual-luciferase report assays showed a target relationship between rno_circRNA_0001004 and miR-709. Furthermore, the rno_circRNA_0001004 overexpression vector and si-circ_0001004 were constructed and transfected into GH3 cells; (3) Results: We found that rno_circRNA_0001004 expression was positively correlated with the PRKCA gene and GH expression levels, while it was negatively correlated with miR-709. In addition, overexpression of rno-circ_0001004 also promoted proliferation and relieved the inhibition of miR-709 in GH3 cells; (4) Conclusions: Our findings show that rno_circ_0001004 acts as a novel sponge for miR-709 to regulate GH synthesis and cell proliferation, and are the first case of discovery of the regulatory role of circRNA_0001004 in pituitary GH.
Recent Progress in Biopolymer-Based Hydrogel Materials for Biomedical Applications
Authors: Mahmood Ayaz , Patel Dev , Hickson Brandon , DesRochers John , Hu Xiao
Published: January 2022

Hydrogels from biopolymers are readily synthesized, can possess various characteristics for different applications, and have been widely used in biomedicine to help with patient treatments and outcomes. Polysaccharides, polypeptides, and nucleic acids can be produced into hydrogels, each for unique purposes depending on their qualities. Examples of polypeptide hydrogels include collagen, gelatin, and elastin, and polysaccharide hydrogels include alginate, cellulose, and glycosaminoglycan. Many different theories have been formulated to research hydrogels, which include Flory-Rehner theory, Rubber Elasticity Theory, and the calculation of porosity and pore size. All these theories take into consideration enthalpy, entropy, and other thermodynamic variables so that the structure and pore sizes of hydrogels can be formulated. Hydrogels can be fabricated in a straightforward process using a homogeneous mixture of different chemicals, depending on the intended purpose of the gel. Different types of hydrogels exist which include pH-sensitive gels, thermogels, electro-sensitive gels, and light-sensitive gels and each has its unique biomedical applications including structural capabilities, regenerative repair, or drug delivery. Major biopolymer-based hydrogels used for cell delivery include encapsulated skeletal muscle cells, osteochondral muscle cells, and stem cells being delivered to desired locations for tissue regeneration. Some examples of hydrogels used for drug and biomolecule delivery include insulin encapsulated hydrogels and hydrogels that encompass cancer drugs for desired controlled release. This review summarizes these newly developed biopolymer-based hydrogel materials that have been mainly made since 2015 and have shown to work and present more avenues for advanced medical applications.
Exogenous Bioactive Peptides Have a Potential Therapeutic Role in Delaying Aging in Rodent Models
Authors: Wang Jianqiang , Wu Yixin , Chen Zhongxu , Chen Yajuan , Lin Qinlu , Liang Ying
Published: January 2022

In recent years, some exogenous bioactive peptides have been shown to have promising anti-aging effects. These exogenous peptides may have a mechanism similar to endogenous peptides, and some can even regulate the release of endogenous active peptides and play a synergistic role with endogenous active peptides. Most aging studies use rodents that are easy to maintain in the laboratory and have relatively homogenous genotypes. Moreover, many of the anti-aging studies using bioactive peptides in rodent models only focus on the activity of single endogenous or exogenous active peptides, while the regulatory effects of exogenous active peptides on endogenous active peptides remain largely under-investigated. Furthermore, the anti-aging activity studies only focus on the effects of these bioactive peptides in individual organs or systems. However, the pathological changes of one organ can usually lead to multi-organ complications. Some anti-aging bioactive peptides could be used for rescuing the multi-organ damage associated with aging. In this paper, we review recent reports on the anti-aging effects of bioactive peptides in rodents and summarize the mechanism of action for these peptides, as well as discuss the regulation of exogenous active peptides on endogenous active peptides.
Hypoxia/Ischemia-Induced Rod Microglia Phenotype in CA1 Hippocampal Slices
Authors: Lana Daniele , Gerace Elisabetta , Magni Giada , Cialdai Francesca , Monici Monica , Mannaioni Guido , Giovannini Maria Grazia
Published: January 2022

The complexity of microglia phenotypes and their related functions compels the continuous study of microglia in diseases animal models. We demonstrated that oxygen-glucose deprivation (OGD) induced rapid, time- and space-dependent phenotypic microglia modifications in CA1 stratum pyramidalis (SP) and stratum radiatum (SR) of rat organotypic hippocampal slices as well as the degeneration of pyramidal neurons, especially in the outer layer of SP. Twenty-four h following OGD, many rod microglia formed trains of elongated cells spanning from the SR throughout the CA1, reaching the SP outer layer where they acquired a round-shaped amoeboid phagocytic head and phagocytosed most of the pyknotic, damaged neurons. NIR-laser treatment, known to preserve neuronal viability after OGD, prevented rod microglia formation. In CA3 SP, pyramidal neurons were less damaged, no rod microglia were found. Thirty-six h after OGD, neuronal damage was more pronounced in SP outer and inner layers of CA1, rod microglia cells were no longer detectable, and most microglia were amoeboid/phagocytic. Damaged neurons, more numerous 36 h after OGD, were phagocytosed by amoeboid microglia in both inner and outer layers of CA1. In response to OGD, microglia can acquire different morphofunctional phenotypes which depend on the time after the insult and on the subregion where microglia are located.
Ten Approaches That Improve Immunostaining: A Review of the Latest Advances for the Optimization of Immunofluorescence
Authors: Piña Ricardo , Santos-Díaz Alma I. , Orta-Salazar Erika , Aguilar-Vazquez Azucena Ruth , Mantellero Carola A. , Acosta-Galeana Isabel , Estrada-Mondragon Argel , Prior-Gonzalez Mara , Martinez-Cruz Jadir Isai , Rosas-Arellano Abraham
Published: January 2022

Immunostaining has emerged as one of the most common and valuable techniques that allow the localization of proteins at a quantitative level within cells and tissues using antibodies coupled to enzymes, fluorochromes, or colloidal nanogold particles. The application of fluorochromes during immunolabeling is referred to as immunofluorescence, a method coupled to widefield or confocal microscopy and extensively applied in basic research and clinical diagnosis. Notwithstanding, there are still disadvantages associated with the application of this technique due to technical challenges in the process, such as sample fixation, permeabilization, antibody incubation times, and fluid exchange, etc. These disadvantages call for continuous updates and improvements to the protocols extensively described in the literature. This review contributes to protocol optimization, outlining 10 current methods for improving sample processing in different stages of immunofluorescence, including a section with further recommendations. Additionally, we have extended our own antibody signal enhancer method, which was reported to significantly increase antibody signals and is useful for cervical cancer detection, to improve the signals of fluorochrome-conjugated staining reagents in fibrous tissues. In summary, this review is a valuable tool for experienced researchers and beginners when planning or troubleshooting the immunofluorescence assay.
Anti-Inflammatory, Antimicrobial, and Vasoconstriction Activities of an Anti-Hemorrhoidal Mixture of Alchemilla vulgaris, Conyza bonariensis, and Nigella sativa: In Vitro and Clinical Evaluations
Authors: Said Omar , Khamaysi Iyad , Kmail Abdalsalam , Sadiq Omar , Saied Besan , Fulder Stephen , Abofarekh Basheer , Masalha Mahmud , Amin Riyad , Saad Bashar
Published: January 2022

Nigella sativa, Conyza bonariensis, and Alchemilla vulgaris are highly recommended in Greco-Arab traditional medicine as anti-hemorrhoid medicinal plants. The efficacy and safety of a topical cream (HPC) consisting of water–ethanol extracts of these three plants were evaluated here in vitro and in a randomized, double-blind, placebo-controlled study (RDBPC). HPC showed no significant cytotoxic effects in fibroblast cell line 3T3 (LDH-release and MTT assay); it inhibited the nitric oxide production by cultured monocyte cell line THP-1 in a dose-dependent manner (reaching the control levels of untreated cells at a concentration of 100 μg/mL). HPC showed a dose-dependent antibacterial activity against Escherichia coli (60% inhibition compared to Ampicillin at 5 mg/disc) and a significant vasoconstriction effect on intestinal vein rings (40% increase compared to phenylephrine). In a RDBPC with 77 hemorrhoidal disease (patients ages 19–61 years with a median grade of hemorrhoids of 2.0), we determined the anti-hemorrhoid efficacy and safety of HPC. The patients were randomly assigned to the HPC group (54 patients) or the placebo group (23 patients). They were asked to apply 2–3 mL of HPC or placebo twice daily for 6 days. The degree of hemorrhoidal disease severity, hemorrhage severity, pain, and itching served as an evaluation of the HPC efficacy. Compared to the placebo group, the obtained results showed that 6 days of treatment with HPC reduced the indexes of hemorrhage severity, severity of pain, and severity of itching to 0–1, 1, and 1 after 6 days, respectively. In conclusion, patients treated with HPC had a significant clinical improvement in all disease severity parameters compared to placebo. In vitro evaluations proved HPC to have significant antimicrobial, anti-inflammatory, and vasoconstriction effects. Therefore, HPC represents an interesting alternative treatment for hemorrhoidal disease.
Knowledge Source Rankings for Semi-Supervised Topic Modeling
Authors: Wood Justin , Arnold Corey , Wang Wei
Published: January 2022

Recent work suggests knowledge sources can be added into the topic modeling process to label topics and improve topic discovery. The knowledge sources typically consist of a collection of human-constructed articles, each describing a topic (article-topic) for an entire domain. However, these semisupervised topic models assume a corpus to contain topics on only a subset of a domain. Therefore, during inference, the model must consider which article-topics were theoretically used to generate the corpus. Since the knowledge sources tend to be quite large, the many article-topics considered slow down the inference process. The increase in execution time is significant, with knowledge source input greater than 103 becoming unfeasible for use in topic modeling. To increase the applicability of semisupervised topic models, approaches are needed to speed up the overall execution time. This paper presents a way of ranking knowledge source topics to satisfy the above goal. Our approach utilizes a knowledge source ranking, based on the PageRank algorithm, to determine the importance of an article-topic. By applying our ranking technique we can eliminate low scoring article-topics before inference, speeding up the overall process. Remarkably, this ranking technique can also improve perplexity and interpretability. Results show our approach to outperform baseline methods and significantly aid semisupervised topic models. In our evaluation, knowledge source rankings yield a 44% increase in topic retrieval f-score, a 42.6% increase in inter-inference topic elimination, a 64% increase in perplexity, a 30% increase in token assignment accuracy, a 20% increase in topic composition interpretability, and a 5% increase in document assignment interpretability over baseline methods.
Two New Species of Batrisini (Coleoptera: Staphylinidae: Pselaphinae) from Nanling Mountain Area, China
Authors: Zhang Wen-Xuan , Yin Zi-Wei
Published: January 2022

Two new species of the Batrisocenus complex of genera, e.g., Batrisceniola nanlingensis sp. nov. and Physomerinus clavipes sp. nov., are described, diagnosed, and illustrated from the Nanling Mountain Area. Both represent a second species of the respective genus from the Chinese mainland.
Pre-Treatment of Fish By-Products to Optimize Feeding of Tenebrio molitor L. Larvae
Authors: Romero-Lorente María-Ángeles , Fabrikov Dmitri , Montes Juan , Morote Elvira , Barroso Fernando G. , Vargas-García María del Carmen , Varga Ágnes Timea , Sánchez-Muros María-José
Published: January 2022

Fish discards are organic waste with high and good-quality protein levels, as well as a fatty acid profile rich in n−3 LCPUFAs, mainly eicosapentaenoic acid and docosahexaenoic acid. These discards can be used as food for Tenebrio molitor (Linnaeus, 1758) larvae, thus increasing the nutritional value of this insect. This study focused on increasing larval acceptance of fish through different pre-treatments of the diets provided, as well as increasing the accumulation of EPA and DHA in fish-fed larvae. Four different diets were prepared: control (broiler feed), DGF50: 50% dried ground fish (Pagellus bogaraveo, Brünnich, 1768) + 50% broiler feed, for different periods, FGF100: 100% fresh ground P. bogaraveo and DUF100: 100% dried whole unground P. bogaraveo. Growth, mortality, proximate composition, fatty acid profile and lipid nutritional indices were determined. Larvae fed with FGF100 displayed better results among treatments, doubling the initial weight, as well as increasing their protein level and decreasing fat levels. Regarding fatty acids, eicosapentaenoic acid and docosahexaenoic acid were only detected in larvae fed with a fish-based diet for a period longer than 5 days. These results show that pre-treatment of fish-based diets causes changes in the growth and compositional parameters of T. molitor larvae.
Cricket Meal (Gryllus bimaculatus) as a Protein Supplement on In Vitro Fermentation Characteristics and Methane Mitigation
Authors: Phesatcha Burarat , Phesatcha Kampanat , Viennaxay Bounnaxay , Matra Maharach , Totakul Pajaree , Wanapat Metha
Published: January 2022

The aim of this work was to conduct the effects of cricket (Gryllus bimaculatus) meal (CM) as a protein supplement on in vitro gas production, rumen fermentation, and methane (CH4) mitigation. Dietary treatments were randomly assigned using a completely randomized design (CRD) with a 2 × 5 factorial arrangement. The first factor was two ratios of roughage to concentrate (R:C at 60:40 and 40:60), and the second factor was the level of CM to replace soybean meal (SBM) in a concentrate ratio at 100:0, 75:25, 50:50, 25:75, and 0:100, respectively. It was found that in vitro DM degradability and the concentration of propionic (C3) were significantly increased (p < 0.05), while the potential extent of gas production (a + b), acetate (C2), acetate and propionate (C2:C3) ratio, and protozoal population were reduced (p < 0.05) by lowering the R:C ratio and the replacement of SBM by CM. In addition, rumen CH4 production was mitigated (p < 0.05) with increasing levels of CM for SBM. In this study, CM has the potential to improve rumen fermentation by enhancing C3 concentration and DM degradability, reduced methane production, and C2:C3 ratio. The effects were more pronounced (p < 0.05) at low levels of roughage.
Development of an MCP-Based Timing Layer for the LHCb ECAL Upgrade-2
Authors: Perazzini Stefano , Ferrari Fabio , Vagnoni Vincenzo Maria ,   on behalf of the LHCb ECAL Upgrade-2 R&D Group
Published: January 2022

The increase in instantaneous luminosity during the high-luminosity phase of the LHC represents a significant challenge for future detectors. A strategy to cope with high-pileup conditions is to add a fourth dimension to the measurements of the hits, by exploiting the time separation of the various proton–proton primary collisions. According to LHCb simulation studies, resolutions of about 10–20 picoseconds, at least an order of magnitude shorter than the average time span between primary interactions, would be greatly beneficial for the physics reach of the experiment. Microchannel plate (MCP) photomultipliers are compact devices capable of measuring the arrival time of charged particles with the required resolution. The technology of large-area picosecond photodetectors (LAPPDs) is under investigation to implement a timing layer that can be placed within a sampling calorimeter module with the purpose of measuring the arrival time of electromagnetic showers. LAPPD performances, using a Gen-I tile with a delay-line anode and a Gen-II with a capacitively coupled anode, have been measured thoroughly both with laser (wavelength of 405 nm and pulse width of 27.5 ps FWHM) and high-energy electron (1–5.8 GeV) beams. Time resolutions of the order of 30 ps for single photoelectrons and 15 ps for electromagnetic showers initiated by 5-GeV electrons, as measured at the shower maximum, are obtained.
Design and Simulation of a Greenhouse FSS Nanofiber Film for Enhancing Agricultural Productivity by Selective Reduction of UV and NIR
Authors: Sripradit Abhisit , Theeradejvanichkul Thorin
Published: January 2022

A greenhouse covering film is an essential part of any greenhouse. Its function is to filter solar radiation in the ultraviolet (UV) and the near-infrared (NIR) bands while allowing a great amount of photosynthetically active radiation (PAR) to transmit. This paper proposes a design of the greenhouse covering film based on a frequency selective surface (FSS). Aluminum is made into fibers in the nanoscale. They are laid out in an array, in-plane at equidistance from one another. This arrangement induces the wavelength selectivity of light via adjustment to the fiber sizes and spacings. The performance is evaluated by a finite element analysis (FEA) method. The results show less than 26% transmittance of UV and NIR while allowing more than 94% transmittance in the PAR regime.
Artificial Endoscopy and Inflammatory Bowel Disease: Welcome to the Future
Authors: Solitano Virginia , Zilli Alessandra , Franchellucci Gianluca , Allocca Mariangela , Fiorino Gionata , Furfaro Federica , D’Amico Ferdinando , Danese Silvio , Al Awadhi Sameer
Published: January 2022

Artificial intelligence (AI) is assuming an increasingly important and central role in several medical fields. Its application in endoscopy provides a powerful tool supporting human experiences in the detection, characterization, and classification of gastrointestinal lesions. Lately, the potential of AI technology has been emerging in the field of inflammatory bowel disease (IBD), where the current cornerstone is the treat-to-target strategy. A sensible and specific tool able to overcome human limitations, such as AI, could represent a great ally and guide precision medicine decisions. Here we reviewed the available literature on the endoscopic applications of AI in order to properly describe the current state-of-the-art and identify the research gaps in IBD at the dawn of 2022.
Prevention of Severe Vestibular Hypofunction after Systemic Gentamicin
Authors: Ferreira-Cendon Sofía , Martinez-Carranza Ramon , Fernandez-Nava Maria José , Villaoslada-Fuente Rosana , Sanchez-Gomez Hortensia , Santa Cruz-Ruiz Santiago , Sanchez-Ledesma María , Batuecas-Caletrio Angel
Published: January 2022

The importance of early evaluation by a neurotologist in patients with infective endocarditis treated with systemic gentamicin and its impact on the patients’ quality of life was evaluated. This is a longitudinal retrospective cohort study of 29 patients who received intravenous gentamicin for the treatment of infective endocarditis. Patients were classified into two groups: group A, before a neurotologist was included in the treatment protocol, and group B, after the inclusion of a neurotologist. The frequency of the different symptoms in each group was measured, and the gain of the vestibulo-ocular reflex (VOR) and its relationship with the presence of oscillopsia. In total, 13 and 16 patients were assigned to groups A and B, respectively. The mean gain of the VOR measured using the video head impulse test in group A was 0.44 in the best side and 0.39 in the worst side. In group B, the mean gain was 0.71 (best side) and 0.64 (worst side) (p < 0.0001). The patients who complained about oscillopsia had a main gain of 0.41 in the best side and 0.35 in the worst side. Evaluation of vestibular function should be included in the infective endocarditis treatment protocol, including the adverse effects of systemic gentamicin.
Iron Deficiency and Reduced Muscle Strength in Patients with Acute and Chronic Ischemic Stroke
Authors: Scherbakov Nadja , Sandek Anja , Valentova Miroslava , Mayer Antje , von Haehling Stephan , Jankowska Ewa , Anker Stefan D. , Doehner Wolfram
Published: January 2022

(1) Introduction: Iron deficiency (ID) contributes to impaired functional performance and reduced quality of life in patients with chronic illnesses. The role of ID in stroke is unclear. The aim of this prospective study was to evaluate the prevalence of ID and to evaluate its association with long-term functional outcome in patients with ischemic stroke. (2) Patients and Methods: 140 patients (age 69 ± 13 years, BMI 27.7 ± 4.6 kg/m², mean ± SD) admitted to a university hospital stroke Unit, with acute ischemic stroke of the middle cerebral artery were consecutively recruited to this observational study. Study examinations were completed after admission (3 ± 2 days after acute stroke) and at one-year follow up (N = 64, 382 ± 27 days after stroke). Neurological status was evaluated according to the National Institute of Health Stroke Scale (NIHSS) and the modified Rankin scale (mRS). Muscle isometric strength of the non-affected limb was assessed by the maximum handgrip test and knee extension leg test. ID was diagnosed with serum ferritin levels ≤ 100 µg/L (ID Type I) or 100–300 µg/L if transferrin saturation (TSAT) < 20% (ID Type II). (3) Results: The prevalence of ID in acute stroke patients was 48% (N = 67), with about two-thirds of patients (N = 45) displaying ID Type I and one-third (N = 22) Type II. Handgrip strength (HGS) and quadriceps muscle strength were reduced in patients with ID compared to patients without ID at baseline (HGS: 26.5 ± 10.4 vs. 33.8 ± 13.2 kg, p < 0.001 and quadriceps: 332 ± 130 vs. 391 ± 143 N, p = 0.06). One year after stroke, prevalence of ID increased to 77% (p = 0.001). While an improvement of HGS was observed in patients with normal iron status, patients with ID had no improvement in HGS difference (4.6 ± 8.3 vs. −0.7 ± 6.5 kg, p < 0.05). Patients with ID remained with lower HGS compared to patients with normal iron status (28.2 ± 12.5 vs. 44.0 ± 8.6 kg, p < 0.0001). (4) Conclusions: Prevalence of ID was high in patients after acute stroke and further increased one year after stroke. ID was associated with lower muscle strength in acute stroke patients. In patients with ID, skeletal muscle strength did not improve one year after stroke.
In-Hospital and One-Year Outcomes of Patients after Early and Late Resuscitated Cardiac Arrest Complicating Acute Myocardial Infarction—Data from a Nationwide Database
Authors: Kowalik Robert , Gierlotka Marek , Ozierański Krzysztof , Trzeciak Przemysław , Fojt Anna , Feusette Piotr , Tycińska Agnieszka , Opolski Grzegorz , Grabowski Marcin , Gąsior Mariusz
Published: January 2022

The prognostic role of early (less than 48 h) resuscitated cardiac arrest (ErCA) complicating acute myocardial infarction (AMI) is still controversial. The present study aimed to analyse the short-term and one-year outcomes of patients after ErCA and late resuscitated cardiac arrest (LrCA) compared to patients without cardiac arrest (CA) complicating AMI. Data from the prospective nationwide Polish Registry of Acute Coronary Syndromes (PL-ACS) were used to assess patients with resuscitated cardiac arrest (rCA) after AMI. Baseline clinical characteristics and the predictors of all-cause death were assessed. The all-cause mortality rate, complications, performed procedures, and re-hospitalisations were assessed for the in-hospital period, 30 days after discharge, and 6- and 12-month follow-ups. Among 167,621 cases of AMI, CA occurred in 3564 (2.1%) patients, that is, 3100 (87%) and 464 (13%) patients with ErCA and LrCA, respectively. The mortality rates in the ErCA vs. LrCA and CA vs. non-CA groups were as follows: in-hospital: 32.1% vs. 59.1% (p < 0.0001) and 35.6% vs. 6.0% (p < 0.0001); 30-day: 2.2% vs. 3.2% (p = 0.42) and 9.9% vs. 5.2% (p < 0.0001); 6-month: 9.2% vs. 17.9% (p = 0.0001) and 12.3% vs. 21.1% (p < 0.0001); and 12-month: 12.3% vs. 21.1% (p = 0.001) and 13% vs. 7.7% (p < 0.0001), respectively. ErCA (hazard ratio (HR): 1.54, confidence interval (CI):1.28–1.89; p < 0.0001) and LrCA (HR: 2.34, CI: 1.39–3.93; p = 0.001) increased the risk of 12-month mortality. During the 12-month follow-up, patients after LrCA more frequently required hospitalisation due to heart failure compared to patients after ErCA. ErCA was related to a higher hospitalisation rate due to coronary-related causes and a higher rate of percutaneous coronary intervention. An episode of LrCA was associated with higher in-hospital and long-term mortality compared to ErCA. ErCA and LrCA were independent risk factors for one-year mortality.
Ammonia and the Muscle: An Emerging Point of View on Hepatic Encephalopathy
Authors: Di Cola Simone , Nardelli Silvia , Ridola Lorenzo , Gioia Stefania , Riggio Oliviero , Merli Manuela
Published: January 2022

In the last years the link between the presence of muscular alterations and hepatic encephalopathy (HE), both minimal and overt, has been deeply studied. The pathophysiological background supporting the relationship between muscle depletion, and HE is characterized by an imbalance between the capacity of muscle in ammonia metabolism and trafficking and the inability of the liver in removing ammonia through urea synthesis due to liver failure and/or the presence of porto-systemic shunts. This review will focus on the clinical burden, the physio pathological mechanisms understanding the liver muscle axis and principles of management of muscular alterations in cirrhosis.
Salivary MicroRNA Signature for Diagnosis of Endometriosis
Authors: Bendifallah Sofiane , Suisse Stéphane , Puchar Anne , Delbos Léa , Poilblanc Mathieu , Descamps Philippe , Golfier Francois , Jornea Ludmila , Bouteiller Delphine , Touboul Cyril , Dabi Yohann , Daraï Emile
Published: January 2022

Background: Endometriosis diagnosis constitutes a considerable economic burden for the healthcare system with diagnostic tools often inconclusive with insufficient accuracy. We sought to analyze the human miRNAome to define a saliva-based diagnostic miRNA signature for endometriosis. Methods: We performed a prospective ENDO-miRNA study involving 200 saliva samples obtained from 200 women with chronic pelvic pain suggestive of endometriosis collected between January and June 2021. The study consisted of two parts: (i) identification of a biomarker based on genome-wide miRNA expression profiling by small RNA sequencing using next-generation sequencing (NGS) and (ii) development of a saliva-based miRNA diagnostic signature according to expression and accuracy profiling using a Random Forest algorithm. Results: Among the 200 patients, 76.5% (n = 153) were diagnosed with endometriosis and 23.5% (n = 47) without (controls). Small RNA-seq of 200 saliva samples yielded ~4642 M raw sequencing reads (from ~13.7 M to ~39.3 M reads/sample). Quantification of the filtered reads and identification of known miRNAs yielded ~190 M sequences that were mapped to 2561 known miRNAs. Of the 2561 known miRNAs, the feature selection with Random Forest algorithm generated after internally cross validation a saliva signature of endometriosis composed of 109 miRNAs. The respective sensitivity, specificity, and AUC for the diagnostic miRNA signature were 96.7%, 100%, and 98.3%. Conclusions: The ENDO-miRNA study is the first prospective study to report a saliva-based diagnostic miRNA signature for endometriosis. This could contribute to improving early diagnosis by means of a non-invasive tool easily available in any healthcare system.