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A number of conditions and factors can cause the transformation of normal cells in the body into malignant tissue by changing the normal functions of a wide range of regulatory, apoptotic, and signal transduction pathways. Despite the current deficiency in fully understanding the mechanism of cancer action accurately and clearly, numerous genes and proteins that are causally involved in the initiation, progression, and metastasis of cancer have been identified. But due to the lack of space and the abundance of details on this complex topic, we have emphasized here more recent advances in our understanding of the principles implied tumor cell transformation, development, invasion, angiogenesis, and metastasis. Inhibition of angiogenesis is a significant strategy for the treatment of various solid tumors, that essentially depend on cutting or at least limiting the supply of blood to micro-regions of tumors, leading to pan-hypoxia and pan-necrosis inside solid tumor tissues. Researchers have continued to enhance the efficiency of anti-angiogenic drugs over the past two decades, to identify their potential in the drug interaction, and to discover reasonable interpretations for possible resistance to treatment. In this review, we have discussed an overview of cancer history and recent methods use in cancer therapy, focusing on anti-angiogenic inhibitors targeting angiogenesis formation. Further, this review has explained the molecular mechanism of action of these anti-angiogenic inhibitors in various tumor types and their limitations use. In addition, we described the synergistic mechanisms of immunotherapy and anti-angiogenic therapy and summarizes current clinical trials of these combinations. Many phase III trials found that combining immunotherapy and anti-angiogenic therapy improved survival. Therefore, targeting the source supply of cancer cells to grow and spread with new anti-angiogenic agents in combination with different conventional therapy is a novel method to reduce cancer progression. The aim of this paper is to overview the varying concepts of cancer focusing on mechanisms involved in tumor angiogenesis and provide an overview of the recent trends in anti-angiogenic strategies for cancer therapy. [ABSTRACT FROM AUTHOR]

Thermoplastic polyurethane (TPU) membrane has super physical-mechanical properties and biocompatibility, but the surface is inert and lack of active groups which limit its application in cell culture. Silk sericin (SS) can improve cell adhesion, proliferation, growth and metabolism. In this paper, SS was grafted onto the surface of TPU membrane by -NH2 bridge to build a high efficiency cell culture membrane. The FT-IR spectrum results indicated SS was grafted by chemical bond. According to the SEM and AFM results, we found that the grafting of SS reduced the water contact angle by 43.31% and increased the surface roughness by about four times. When TPU-SS was used for HepG2 cell culture, the cell adhesion rate of TPU-SS was significantly higher than that of the general TCPS cell culture plate, and the cell proliferation rate was close to that of TCPS. FDA/EB staining showed that HepG2 cells remained a better cellular growth behavior. HepG2 cells had higher cell vitality including the albumin secretion and the intracellular total protein synthesis. Grafting SS maintained the stability of cell and significantly decreased the cytotoxicity by decreased LDH release. In conclusion, SS grafting is beneficial to cell culture in vitro, and provides a key material for bioartificial liver culture system. [ABSTRACT FROM AUTHOR]

Nanoarchitectonics has emerged as a post-nanotechnology concept. As one of the applications of nanoarchitectonics, this review paper discusses the control of stem cell fate and function as an important issue. For hybrid nanoarchitectonics involving living cells, it is crucial to understand how biomaterials and their nanoarchitected structures regulate behaviours and fates of stem cells. In this review, biomaterials for the regulation of stem cell fate are firstly discussed. Besides multipotent differentiation, immunomodulation is an important biological function of mesenchymal stem cells (MSCs). MSCs can modulate immune cells to treat multiple immune- and inflammation-mediated diseases. The following sections summarize the recent advances of the regulation of the immunomodulatory functions of MSCs by biophysical signals. In the third part, we discussed how biomaterials direct the self-organization of pluripotent stem cells for organoid. Bioactive materials are constructed which mimic the biophysical cues of in vivo microenvironment such as elasticity, viscoelasticity, biodegradation, fluidity, topography, cell geometry, and etc. Stem cells interpret these biophysical cues by different cytoskeletal forces. The different cytoskeletal forces lead to substantial transcription and protein expression, which affect stem cell fate and function. Regulations of stem cells could not be utilized only for tissue repair and regenerative medicine but also potentially for production of advanced materials systems. Materials nanoarchitectonics with integration of stem cells and related biological substances would have high impacts in science and technology of advanced materials. [ABSTRACT FROM AUTHOR]

Exosomes are a class of extracellular vesicles with a diameter of 50–100 nm secreted by various cells. They are generated through complex intracellular production mechanisms before being secreted to the extracellular environment. Due to their inclusion of proteins, lipids, and nucleic acids, exosomes play an important role in intercellular communication. Pancreatic β-cells play an irreplaceable role in the body's glucose metabolism. Their dysfunction is one of the causes of diabetes. Exosomes of various cells regulate the function of β-cells by regulating autoimmunity, delivering non-coding RNAs, or directly regulating intracellular signal pathways. This communication between β-cells and other cells plays an important role in the pathogenesis and development of diabetes, and has potential for clinical application. This paper reviews the biological sources and functions of exosomes, as well as intercellular crosstalk between β-cells and other cells that is involved in β-cell failure and regeneration. [ABSTRACT FROM AUTHOR]

In the human body, maintaining the core body temperature (CBT) is vital to ensure proper cellular and body functions. The temperature of 37°C (98°F) is the well-established baseline for CBT, but significant deviations to under 35°C (95°F) or over 40°C (104°F) can result in several health complications. If unnoticed in spaceflight, astronauts CBT could reach dangerously high levels when doing physically challenging tasks such as spacewalking or exercise. Therefore, a real-time multi-physiological parameter sensing system is needed to noninvasively monitor the status of crew members in space. The purpose of this paper is to test a novel temperature sensor developed by integrating thin sheets of polyvinylidene fluoride (PVDF), a temperature dependent dielectric material, into the sensor system designed as a substrate. This substrate interacts with the electromagnetic field created by the spiral sensor to result in a quantitative temperature monitoring sensor with a resolution of 1°C. [ABSTRACT FROM AUTHOR]

Carbon nanomaterials are an inventive class of materials with wide applications in state-of-the-art bioimaging and therapeutics. They allow a broad range of tunable and integrated advantages of structural flexibility, chemical and thermal stability, upright electrical conductivity, and the option of scale-up and mass production. In the context of nanomedicine, carbon nanomaterials have been used extensively to mitigate the serious side effects of conventional chemotherapy and also to enable early cancer diagnostics, given their wide range of tunable properties. A class of carbon nanomaterials, called carbon dots (CDs) are small carbon-based nanoparticles and have been a valued discovery due to their photoluminescence, low photobleaching, and high surface area to mass ratio. The process of producing these CDs had so far been a high energy demanding process involving wet chemistry for purification. A one-step tunable production of luminescent CDs from fuel rich combustion reactors was recently presented by our group. In this paper, we explore the effects of these yellow luminescent combustion-generated CDs in MCF7 adenocarcinoma and MCF10a normal breast epithelial cells. We observed that these CDs, also at nontoxic doses, can affect basic cellular functions, such as cell cycle and proliferation; induce substantial changes on the physical parameters of the plasma membrane; and change the overall appearance of a cell in terms of morphology. [ABSTRACT FROM AUTHOR]

Nanofibrous biomaterials, because of their structural similarity to the extracellular matrix, can be employed as a scaffold in tissue engineering. The use of biopolymers to nanofibers fabrication attracts a great deal of attention. However, sometimes these nanofibers do not support specific cell behaviors. To address this drawback, surface modification of these structures has been actively investigated. Just a while ago, nanofibrous scaffolds have been modified employing various techniques to provide an appropriate microenvironment for protecting cell functions. Modification of bulk or surfaces of the nanofibrous scaffolds via different methods can promote cell adhesion, growth, proliferation, migration, and differentiation. In this paper, we are going to discuss the different and new approaches to surface modification of polymeric nanofibers that can influence scaffolds characteristics. Surface modification of nanofibrous scaffolds can improve physical & chemical properties especially cellular behaviors. [ABSTRACT FROM AUTHOR]

A protein complex is a collection of two or more associated proteins that interact with each other in a stable long-term interaction. Protein complexes have essential roles in regulatory processes, cellular functions and signaling cascades. This paper examines how well-known collections of protein complexes are supported in protein–protein interaction (PPI) networks, i.e. whether they form connected subnetworks in a particular PPI network. For that purpose, we apply a variable neighbourhood search (VNS) metaheuristic algorithm for adding the minimum number of interactions in order to support protein complexes. Experimental results obtained on several PPI networks (BioGRID, WI-PHI and String) and four protein complex standards (MIPS, TAP06, SGD and CYC2008) show that considered networks do not include enough PPIs to support all complexes from complex standards. Deeper analysis indicates that there exists common PPIs which are probably missing in the considered networks. These findings can be useful for further biological interpretation and developing of PPI prediction models. [ABSTRACT FROM AUTHOR]

Chaperonin containing TCP1 subunit 6A (CCT6A) was recently discovered to be involved in cancer pathogenesis and stemness; however, its role in oral squamous cell carcinoma (OSCC) has not been reported. The current study aimed to investigate the impact of CCT6A on OSCC cell malignant behaviors and stemness and to explore its potentially interreacted pathways. SCC-15 and HSC-3 cells were transfected with the plasmid loading control overexpression, CCT6A overexpression, control knockout, or CCT6A knockout. Wnt4 overexpression or Notch1 overexpression plasmids were transfected into CCT6A-knockout SCC-15 cells. Cell proliferation, apoptosis, invasion, stemness, Notch, and Wnt pathways were detected in both cell lines, whereas RNA sequencing was only performed in SCC-15 cells. CCT6A was upregulated in five OSCC cell lines, including SCC-15, HSC-3, SAT, SCC-9, and KON, compared to that in the control cell line. In SCC-15 and HSC-3 cells, CCT6A overexpression increased cell proliferation, invasion, sphere formation, CD133, and Sox2 expression, but decreased cell apoptosis; on the contrary, CCT6A knockout exhibited an opposite effect on the above indexes. RNA-sequencing data revealed that the Wnt and Notch pathways were involved in the CCT6A'effect on SCC-15 cell functions. CCT6A positively regulates the Wnt and Notch pathways in SCC-15 and HSC-3 cells. Importantly, it was shown that activation of the Wnt or Notch pathways attenuated the effect of CCT6A knockout on SCC-15 cell survival, invasion, and stemness. CCT6A may promote OSCC malignant behavior and stemness by activating the Wnt and Notch pathways. [ABSTRACT FROM AUTHOR]

Rising obesity levels, worldwide, are resulting in substantial increases in cardiovascular disease, diabetes, kidney disease, musculoskeletal disorders, and certain cancers, and obesity-associated illnesses are estimated to cause ∼4 million deaths worldwide per year. A common theme in this disease epidemic is the chronic systemic inflammation that accompanies obesity. CD4+ Foxp3+ regulatory T cells residing in visceral adipose tissues (VAT Tregs) are a unique immune cell population that play essential functions in restricting obesity-associated systemic inflammation through regulation of adipose tissue homeostasis. The distinct transcriptional program that defines VAT Tregs has been described, but directly linking VAT Treg differentiation and function to improving insulin sensitivity has proven more complex. Here we review new findings which have clarified how VAT Tregs differentiate, and how distinct VAT Treg subsets regulate VAT homeostasis, energy expenditure, and insulin sensitivity. [ABSTRACT FROM AUTHOR]

A novel method for predicting effective stiffnesses of composite plates with in-plane periodicity is proposed according to two-scale strain energy equivalence. The macroscale energy is reached with the Reissner-Mindlin plate theory, while the microscale energy is obtained through the newly constructed displacement functions of a unit cell within the framework of the three-dimensional elasticity theory. The new displacement functions consist of homogenized displacements, two decoupled expansion terms, and a higher-order perturbed displacement term. The elaborate finite element formulations are presented for realizing the present method in Comsol Multiphysics. Several numerical experiments demonstrate the effectiveness of the new stiffness prediction method. [ABSTRACT FROM AUTHOR]

The moisture content of wood is changed during manufacturing processes, such as drying and impregnation. Understanding the water transport in wood is helpful for optimizing the manufacturing technology and improving the durability of wood products. Herein, the one-side imbibition tests of Chinese fir and poplar were carried out via direct contact with a water-saturated sponge. Imbibition amounts and orthotropic kinetics were evaluated by X-ray densitometry, where wood exhibited non-uniform and directional behaviors for water imbibition and there were variations in behavior between Chinese fir and poplar. More water uptake and faster migration were observed for poplar, while water preferentially accumulated at the wetting front for Chinese fir. The effective imbibition height of poplar was significantly higher than Chinese fir, regardless of orientation direction. Within the growth rings, Chinese fir showed heterogeneous water uptake, and faster water migration in latewood was observed. Imbibition height in a single fiber was simulated as a function of cell wall ratio, and the influences of anatomical factors on water movement were explored. These simulation assessments were consistent with the results of the one-side imbibition tests. These findings help to explain the water transport mechanism at the mesoscale and interactions between wood and water. [ABSTRACT FROM AUTHOR]

Targeted monoclonal antibody therapy has emerged as a powerful therapeutic strategy for cancer. However, only a minority of patients have durable responses and the development of resistance remains a major clinical obstacle. Antibody-dependent cell-mediated cytotoxicity (ADCC) represents a crucial therapeutic mechanism of action; however, few studies have explored ADCC resistance. Using multiple in vitro models of ADCC selection pressure, we have uncovered both shared and distinct resistance mechanisms. Persistent ADCC selection pressure yielded ADCC-resistant cells that are characterized by a loss of NK cell conjugation and this shared resistance phenotype is associated with cell-line dependent modulation of cell surface proteins that contribute to immune synapse formation and NK cell function. We employed single-cell RNA sequencing and proteomic screens to interrogate molecular mechanisms of resistance. We demonstrate that ADCC resistance involves upregulation of interferon/STAT1 and DNA damage response signaling as well as activation of the immunoproteasome. Here, we identify pathways that modulate ADCC sensitivity and report strategies to enhance ADCC-mediated elimination of cancer cells. ADCC resistance could not be reversed with combinatorial treatment approaches. Hence, our findings indicate that tumor cells utilize multiple strategies to inhibit NK cell mediated-ADCC. Future research and development of NK cell-based immunotherapies must incorporate plans to address or potentially prevent the induction of resistance. [ABSTRACT FROM AUTHOR]

Circular RNA (circRNA) forms closed loops via back-splicing in precursor mRNA, resisting exonuclease degradation. In higher eukaryotes, protein-coding genes create circRNAs through exon back-splicing. Unlike mRNAs, circRNAs possess unique production and structural traits, bestowing distinct cellular functions and biomedical potential. In this review, we explore the pivotal roles of viral circRNAs and associated RNA in various biological processes. Analysing the interactions between viral circRNA and host cellular machinery yields fresh insights into antiviral immunity, catalysing the development of potential therapeutics. Furthermore, circRNAs serve as enduring biomarkers in viral diseases due to their stable translation within specific tissues. Additionally, a deeper understanding of translational circRNA could expedite the establishment of circRNA-based expression platforms, meeting the rising demand for broad-spectrum viral vaccines. We also highlight the applications of circular RNA in biomarker studies as well as circRNA-based therapeutics. Prospectively, we expect a technological revolution in combating viral infections using circRNA. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the most common cancers and has continued to increase in incidence worldwide. Moreover, the involvement of microRNAs (miRs) has been reported in the development and progression of HCC. Here, we investigated the role of miR-206 in HCC growth and metastasis. HCC-related microarray datasets were harvested to screen differentially expressed miRNAs in HCC samples followed by prediction of downstream target genes. The dual-luciferase reporter assay verified the target-binding relationship between miR-206 and CREB5. The human HCC cell line MHCC97-H was cultured in vitro and transfected with miR-206 mimic/inhibitor or sh-/oe-CREB5 for analyzing MHCC97-H cell biological functions. The orthotopic xenograft model of HCC mice was constructed to observe the tumorigenic ability of HCC cells in vivo. Bioinformatics analysis found that miR-206 may be involved in HCC growth and metastasis by targeting CREB5 and regulating PI3K/AKT signaling pathway. In vivo animal experiments found that CREB5 was significantly overexpressed in mouse HCC tissues. In HCC cells, miR-206 can target down-regulate the expression of CREB5, thereby inhibiting the activation of PI3K/AKT signaling pathway. Furthermore, in vitro cell experiments confirmed that overexpression of miR-206 could inhibit the PI3K/AKT signaling pathway by down-regulating CREB5 expression, thereby inhibiting the proliferation, migration and invasion of HCC cells. In conclusion, our results revealed that miR-206 could down-regulate the expression of CREB5 and inhibit the activation of PI3K/AKT signaling pathway, thereby preventing HCC growth and metastasis. Abbreviations: HCC: hepatocellular carcinoma; HBV or HCV: hepatitis B or C virus; miRNAs: microRNAs; CREB: cAMP response element-binding protein; CRE: cAMP response elements [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is associated with increased atherogenicity and inflammatory responses, which may be related to high mobility group box 1 (HMGB1) and Dickkopf-related protein 1 (DKK1). The role of HMGB1 and DKK1 in T2DM is examined in association with lipid and insulin profiles. Serum HMGB1 and DKK1 were measured in T2DM with and without hypertension and compared with controls. The results showed that HMGB1 and DKK1 are higher in T2DM irrespective of hypertension. A large part of the variance in the β-cell index and glucose toxicity was explained by the combined effects of HMGB1 and DKK1. In conclusion, both HMGB1 and DKK1 may contribute to increased atherogenicity in T2DM. Moreover, both biomarkers may cause more deficits in β-cell function and increase glucose toxicity leading to the development of more inflammation and diabetic complications. HMGB1 and the Wnt pathways are other drug targets in treating T2DM. [ABSTRACT FROM AUTHOR]

We aimed to determine the effects of exercise training on the function of vascular smooth muscle cells. PubMed and Web of Science about the effects of exercise training on vascular smooth muscle cells were searched up to August 2020. The effect sizes were estimated in terms of the standardized mean difference. The number of studies included was thirty-five overall. Exercise training had positive effects on vascular smooth muscle cells function in participants older than 40. Effect sizes for HIGH intensity and MIX were positive but small, and also when training duration was longer than 12 weeks. We concluded that vascular smooth muscle cells response can be promoted by exercise training. Vigorous aerobic exercise and mixture training modality were the best ways to promote the dilation response of vascular smooth muscle cells. Additionally, the significant improvement induced by exercise training only occurred when training lasted for longer than 12 weeks. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are small, non-coding RNAs, able to regulate cellular functions by induction of mRNA degradation and post-transcriptional repression of gene expression. Platelets are the major source of circulating miRNAs, with significant regulatory potential on cardiovascular pathophysiology and other diseases. MiRNAs have been shown to modify the expression of platelet proteins, which influence the platelets reactivity. Circulating miRNAs can be determined from plasma, serum, or whole blood, and they can be used as diagnostic and prognostic biomarkers as well as therapeutic targets including cardiovascular diseases (CVDs). Herein, we present original results from bioinformatic analyses, which identified top 22 platelet-related miRNAs including hsa-miR-320a, hsa-miR-16-5p, hsa-miR-106a-5p, hsa-miR-320b, hsa-miR-15a-5p, hsa-miR-15b-5p, hsa-miR-195-5p, hsa-miR-92a-3p as widely involved in platelet reactivity and associated diseases, including CVDs, Alzheimer's and cerebrovascular diseases, cancer and hypertension. Analysis focused on the identification of the highly regulatory targets shared between those miRNAs identified 43 of them. Best ranked genes associated with overall platelet activity and most susceptible for noncoding regulation were PTEN, PIK3R1, CREB1, APP, and MAPK1. Top targets also strongly associated with CVDs were VEGFA, IGF1, ESR1, BDNF, and PPARG. Top targets associated with other platelet-related diseases including cancer identified in our study were TP53, KRAS, and CCND1. The most affected pathways by top miRNAs and top targets included diseases of signal transduction by Growth Factor Receptors (GDFRs) and second messengers, platelet activation, signaling, and aggregation, signaling by VEGF, MAPK family signaling cascades, and signaling by Interleukins. Terms specific only for platelet-related miRNAs included coronary artery disease, platelet degranulation, and neutrophil degranulation, while for the top platelet-related genes it was Estrogen Signaling Receptor (ESR) mediated signaling, extra-nuclear estrogen signaling, and endometriosis. Our results show the novel features of platelet physiology and may provide a basis for further clinical studies focused on platelet reactivity. They also show in which aspects miRNAs can be promising biomarkers of platelet-related pathological processes. [ABSTRACT FROM AUTHOR]

Scientific research looks for answers to broaden our knowledge, and the specific questions addressed in each study are those that distinguish the type of scientific investigation pursued. In the field of ecophysiology biological functions are addressed, cell strategies of adaptation and acclimation to environmental changes are explored, the roles of biotic and abiotic factors on evolutionary trajectories of organisms are investigated. In line with the ecophysiological approach, the papers included in this issue explore the taxonomic and functional diversity of algae, reflecting and following the deep interest of professor Mario Giordano in aquatic autotrophic organisms. [ABSTRACT FROM AUTHOR]

Like other cancers, considerable effort has been made in acute myeloid leukemia (AML) to identify prognostic genes and long noncoding RNAs (lncRNAs) with their potential clinical applications. However, to date, no integrated prognostic model has been developed that combines both gene expression and lncRNAs as a singular approach in AML. Comprehensive bioinformatic approaches (Weighted gene co-expression network analysis, Univariate Cox regression analyses, Pearson correlation, LASSO-Cox regression, Wilcoxon test) were used to construct the signature and to define high- and low-risk groups in AML datasets. ESTIMATE and CIBERSORT algorithms were applied to investigate the potential impact of infiltrating immune cells based on the obtained signature in tumor microenvironment. In addition, gene ontology (GO) and KEGG enrichment were applied to explore the potential function of the signature. Herein, we focused on immune-related genes (IRGs) and immune-related long noncoding RNAs (IRlncRNAs) and constructed an integrated prognostic immunorelevant signature in AML. The obtained signature exhibit five IRGs (DAXX, PSMB8, CSRP1, RAC2 and PTPN6) and one IRlncRNA (AC080037.2) and is strictly associated with age and FAB (French–American–British classification). Importantly, the high-risk AML group (defined by the signature) correlated positively with three types of scores (immune score, stroma score, and ESTIMATE score). We also identified a few immune cells (resting mast cells and monocytes) potentially involved in the correlation between signature and survival of AML patients. The prognostic ability of the obtained signature was tested in the training cohort and then validated in both test and total cohorts. The pathway enrichment analysis confirmed the possible immune- related role of the signature. We constructed an integrated prognostic signature comprising five immune-related protein-coding genes (IRPCG) (DAXX, PSMB8, CSRP1, RAC2, and PTPN6) and one immune-related lncRNA (AC080037.2) that may serve as potential biomarkers for predicting survival and further stratifying AML patients. [ABSTRACT FROM AUTHOR]

Cervical cancer (CC) is a severe malignant tumor. Recently, more and more evidence has shown that abnormal expression of fatty acid synthase (FASN) occurs in varying tumors. Therefore, this investigation devoted to FASN in CC along with its upstream regulatory miRNA. Their expression levels were tested by qRT-PCR. Cell function experiments were undertaken to test tumor-related cell behaviors. Identification of their interplay was conducted by western blot and dual-luciferase methods. As analyzed, miR-497-5p was at low level in human CC cell lines, while FASN was overexpressed and demonstrated as a target of miR-497-5p. Cell function experiments demonstrated the targeting of miR-497-5p to FASN 3′-UTR, thus restraining CC development. To sum up, this investigation primarily revealed miR-497-5p/FASN axis in CC, by which potential CC biomarkers, could be developed. However, the mechanism of the axis was not determined in vivo, as one of the study limitations. [ABSTRACT FROM AUTHOR]

First discovered on macrophages by Goldstein and Brown in 1979, Scavenger Receptors have since been shown to participate in a diverse number of cell functions; equally diverse are their structures and the ligands they bind. Macrophage activation is crucial in the outcome of an immune response. SR-A1 is highly abundant on macrophages and recognizes both host- and microorganism-derived molecules that impact processes that are initiated, perpetuated, or modified. This review summarizes the involvement of SR-A1 in both inflammatory and anti-inflammatory responses, the multiple-ligand internalization mechanisms and the diversity of signaling pathways that impact macrophage function and activation. Engagement of SR-A1 results in the stimulation of differential signaling pathways and patterns of cytokine expression, kinetics, magnitude of response and activation status. SR-A1 plays essential roles in phagocytosis and efferocytosis, interacting with other receptors and promoting tolerance in response to apoptotic cell uptake. In cell adhesion, tissue remodeling, and cell migration, SR-A1 signals through different pathways engaging different cytoplasmic motifs. We describe the role of SR-A1 during innate and adaptive immune responses, such as participation in macrophage polarization and interaction with other innate receptors, as well as in antigen uptake, processing, and presentation, regulating T and B cell activation. The dichotomous contribution of SR-A1 on macrophage functions is discussed. A better understanding of the role SR-A1 plays through molecular mechanisms and crosstalk with other receptors may provide insights into developing novel therapeutic strategies to modulate immune responses and immunopathologies. [ABSTRACT FROM AUTHOR]

The first order derivatives of a Digital Elevation Model (DEM) defined over a regular grid are usually computed without an uncertainty estimate. The standard procedure involves a compact 3 × 3 window. Using a Taylor expansion, an uncertainty interval for each partial derivative as a function of the cell size was devised using two estimates, either of different resolution or of different order. The intervals for slope and aspect can be derived afterwards. We carried out an experiment comparing some different estimates of the slope and aspect over a synthetic surface representative of a real topography and amenable to offer an exact derivative. The partial derivatives were numerically estimated with four different procedures: the Simple procedure defined by Jones over a 2 × 2 window, the Evans–Young procedure using a centered difference over a 3 × 3 window, and using a 5 × 5 window both with an extrapolated Evans–Young procedure and the expression due to Florinsky. The results confirm that intervals for both slope and aspect always included the exact value even after drastically increasing the cell size. Finally, a real case with an integer-valued DEM was considered, illustrating the combined effect of Representation and Truncation error. [ABSTRACT FROM AUTHOR]

For cell and tissue physiology research, drug discovery, and growing replacement tissues for regenerative medicine, accurate and cost-efficient in vitro techniques are increasingly demanded. The conventional model for in vitro cell culture is the two-dimensional (2D) culture. Yet, cells have been found to be more native when they are grown in 3D conditions. We present here the development and evaluation of biological properties of bacterial cellulose/hydroxyapatite (BC/HA) nanocomposite hydrogel as a potential 3D cell-culture platform. The synthesized composites were characterized using Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM), Swelling measurements and Celltiter 96® Aqueous One Solution Cell Proliferation Assay (MTS) using mouse fibroblast cell line (L – 929). The arrangement of composites shown in SEM and AFM images closely resembles the native extracellular matrices (ECM) showing the potential to act as a viable substrate for cell culture. The composites exhibited high swelling ratio (5.31–5.81), indicating enhanced moisture absorption and potential for nutrient exchange. The in vitro biocompatibility results indicated significantly high percentage cell proliferation (85.20%-88.30%). These findings indicate that the BC/HA composites are potential candidates for 3D cell-culture applications. [ABSTRACT FROM AUTHOR]

Germline-encoded pattern recognition receptors [PRRs] in mammalian cells function in the detection of molecular patterns associated with pathogen invasion or cellular damage. A PRR subset is activated by the atypical presence and location of double-stranded RNA [dsRNA] or its synthetic analogue polyinosinic-polycytidylic acid [poly(I:C)], triggering pro-inflammatory signalling and death in many cell types. Poly(I:C) has been tested as a sole or combination cancer therapy in preclinical studies and clinical trials. The purpose of this study was to evaluate the effects of poly(I:C) transfection via electroporation on cell lines from a cancer of epithelial origin, 4T1 mammary carcinoma, and a cancer of mesenchymal origin, WEHI 164 fibrosarcoma. The effects of the poly(I:C) delivery on cell metabolism implicate the induction of cell death. A pro-inflammatory response was demonstrated by mRNA upregulation and the secretion of Type I interferon and several cytokines and chemokines. The mRNAs of dsRNA sensor DExD/H-box helicase 58/retinoic acid-inducible gene I protein [Ddx58/RIG-I] and sensor/co-sensor DEAH-box helicase 9 [Dhx9] were not regulated, but the mRNAs of RNA sensors toll-like receptor 3 [TLR3], interferoninduced with helicase C domain 1/melanoma differentiation-associated protein 5 [Ifih1/MDA5] and Z-DNA binding protein 1 [Zbp1] and co-sensors DEAD (Asp-Glu-Ala-Asp) box polypeptide 60 [Ddx60] and interferon-inducible protein 204 [Ifi204] were upregulated in both cell lines. The mRNAs encoding signalling pathways components were present or upregulated in both cell types. These data demonstrate that RNA sensing effects can be amplified by electroporation delivery, potentially expanding the practicality of this immunotherapeutic approach. [ABSTRACT FROM AUTHOR]

It has recently been shown that CFIm25, a canonical mRNA 3' processing factor, could play a variety of physiological roles through its molecular function in the regulation of mRNA alternative polyadenylation (APA). Here, we used CRISPR/Cas9-mediated gene editing approach in human embryonic stem cells (hESCs) for CFIm25, and obtained three gene knockdown/mutant cell lines. CFIm25 gene editing resulted in higher proliferation rate and impaired differentiation potential for hESCs, with these effects likely to be directly regulated by the target genes, including the pluripotency factor rex1. Mechanistically, we unexpected found that perturbation in CFIm25 gene expression did not significantly affect cellular mRNA 3' processing efficiency and APA profile. Rather, we provided evidences that CFIm25 may impact RNA polymerase II (RNAPII) occupancy at the body of transcribed genes, and promote the expression level of a group of transcripts associated with cellular proliferation and/or differentiation. Taken together, these results reveal novel mechanisms underlying CFIm25's modulation in determination of cell fate, and provide evidence that the process of mammalian gene transcription may be regulated by an mRNA 3' processing factor. [ABSTRACT FROM AUTHOR]

Latent 5' splice sites, not normally used, are highly abundant in human introns, but are activated under stress and in cancer, generating thousands of nonsense mRNAs. A previously proposed mechanism to suppress latent splicing was shown to be independent of NMD, with a pivotal role for initiator-tRNA independent of protein translation. To further elucidate this mechanism, we searched for nuclear proteins directly bound to initiator-tRNA. Starting with UV-crosslinking, we identified nucleolin (NCL) interacting directly and specifically with initiator-tRNA in the nucleus, but not in the cytoplasm. Next, we show the association of initiator-tRNA and NCL with pre-mRNA. We further show that recovery of suppression of latent splicing by initiator-tRNA complementation is NCL dependent. Finally, upon nucleolin knockdown we show activation of latent splicing in hundreds of coding transcripts having important cellular functions. We thus propose nucleolin, a component of the endogenous spliceosome, through its direct binding to initiator-tRNA and its effect on latent splicing, as the first protein of a nuclear quality control mechanism regulating splice site selection to protect cells from latent splicing that can generate defective mRNAs. [ABSTRACT FROM AUTHOR]

Simultaneous measurement of multiple modalities in single-cell analysis, represented by CITE-seq, is a promising approach to link transcriptional changes to cellular phenotype and function, requiring new computational methods to define cellular subtypes and states based on multiple data types. Here, we design a flexible single-cell multimodal analysis framework, called CITEMO, to integrate the transcriptome and antibody-derived tags (ADT) data to capture cell heterogeneity from the multi omics perspective. CITEMO uses Principal Component Analysis (PCA) to obtain a low-dimensional representation of the transcriptome and ADT, respectively, and then employs PCA again to integrate these low-dimensional multimodal data for downstream analysis. To investigate the effectiveness of the CITEMO framework, we apply CITEMO to analyse the cell subtypes of Cord Blood Mononuclear Cells (CBMC) samples. Results show that the CITEMO framework can comprehensively analyse singlecell multimodal samples and accurately identify cell subtypes. Besides, we find some specific immune cells that co-express multiple ADT markers. To better describe the co-expression phenomenon, we introduce the co-expression entropy to measure the heterogeneous distribution of the ADT combinations. To further validate the robustness of the CITEMO framework, we analyse Human Bone Marrow Cell (HBMC) samples and identify different states of the same cell type. CITEMO has an excellent performance in identifying cell subtypes and states for multimodal omics data. We suggest that the flexible design idea of CITEMO can be an inspiration for other single-cell multimodal tasks. The complete source code and dataset of the CITEMO framework can be obtained from https://github. com/studentiz/CITEMO. [ABSTRACT FROM AUTHOR]

Mitochondria are organelles that play a crucial role in cell physiology, cell death, and aging. They are among the first responders to different stressors that originate from the environment. Cadmium as a heavy metal affects different levels of body organization: from organs through tissues and cells to organelles. Based on our previous research results, we decided to check how the exposure to cadmium affects the functioning of mitochondria in different organs of soil living centipede Lithobius forficatus. The activity of mitochondria in somatic and germ cells has been analyzed using transmission electron microscopy (TEM), confocal microscopy, and flow cytometry. Changes in the mitochondrial membrane potential and mitochondrial dismutase (MnSOD) activity in relation to the accumulation of reactive oxygen species (ROS) caused by cadmium exposure have been studied. Individuals were divided into 3 experimental groups depending on cadmium concentration in soil. Changes in mitochondrial ultrastructure caused by cadmium are tissue-dependent and associated with an increase of ROS levels. The system of ROS and MnSOD activation works more efficiently in the case of gonads than in the digestive system. While the short-term cadmium exposure alters the fine structure of both the somatic and germ-line cells in gonads, the long-term cadmium exposure causes mitochondrial ultrastructure regeneration. [ABSTRACT FROM AUTHOR]

Candida albicans is a common commensal on human mucosal surfaces, but can become pathogenic, e.g. if the host is immunocompromised. While neutrophils, macrophages and T cells are regarded as major players in the defense against pathogenic C. albicans, the role of B cells and the protective function of their antibodies are less well characterized. In this study, we show that human serum antibodies are able to enhance the association of human THP-1 monocyte-like cells with C. albicans cells. Human serum antibodies are also capable of inhibiting the adherence and damage dealt to epithelial cells. Furthermore, human serum antibodies impair C. albicans invasion of human oral epithelial cells by blocking induced endocytosis and consequently host cell damage. While aspartic proteases secreted by C. albicans are able to cleave human IgG, this process does not appear to affect the protective function of human antibodies. Thus, humans are equipped with a robust antibody response to C. albicans, which can enhance antifungal activities and prevent fungal-mediated epithelial damage. [ABSTRACT FROM AUTHOR]

The small non-coding vault RNA (vtRNA) is a component of the vault complex, a ribonucleoprotein complex found in most eukaryotes. vtRNAs regulate a variety of cellular functions when unassociated with the vault complex. Human has four vtRNA paralogs (hvtRNA1-1, hvtRNA1-2, hvtRNA1-3, hvtRNA2-1), which are highly similar and differ only slightly in primary and secondary structure. Despite the increasing research on vtRNAs, a feature that distinguishes one hvtRNA from the others has not been recognized. Recently, we demonstrated that murine vtRNA (mvtRNA) promotes synapse formation by modulating the MAPK signaling pathway. Here we showed that expression ofhvtRNA1-1, but not hvtRNA2-1 increases the expression of synaptic marker proteins, ERK phosphorylation and the number of PSD95 and Synapsin I double positive puncta to an extent similar to that of mvtRNA, suggesting that hvtRNA1-1 may enhance synapse formation. This finding opens new perspectives to uncover the function of the different vtRNA paralogs. [ABSTRACT FROM AUTHOR]

RASAL2 (RAS protein activator like 2), a RASGTPase activating protein, can catalyze the hydrolysis of RAS-GTP into RAS-GDP to inactivate the RAS pathway in various types of cancer cells. However, the cellular function of RASAL2 remains elusive. Here we showed that RASAL2 can attenuate PRKAA/AMPKα phosphorylation by recruiting phosphatase PPM1B/pp2cβ, thus inhibiting the initiation of basal autophagy under normal conditions. In addition, we found that glucose starvation could induce dissociation of PPM1B from RASAL2 and then RASAL2 at S351 be phosphorylated by PRKAA, followed by the binding of phosphorylated-RASAL2 with to PIK3C3/VPS34-ATG14-BECN1/Beclin1 complex to increase PIK3C3 activity and autophagy. Furthermore, RASAL2 S351 phosphorylation facilitated breast tumor growth and correlated to poor clinical outcomes in breast cancer patients. Our study demonstrated that the phosphorylation status of RASAL2 S351 can function as a molecular switch to either suppress or promote AMPK-mediated autophagy. Inhibition of RASAL2 S351 phosphorylation might be a potential therapeutic strategy to overcome the resistance of AMPK-activation agents. Abbreviations: AICAR: aminoimidazole carboxamide ribonucleotide; AMPK: adenosine 5'-monophosphate (AMP)-activated protein kinase; ATG14: autophagy related 14; C.C: compound C; CQ: chloroquine; DKO: double-knockout; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MTOR: mechanistic target of rapamycin kinase; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; PIK3R4/VPS15: phosphoinositide-3-kinase regulatory subunit 4; PPM1B/pp2cβ: protein phosphatase, Mg2+/Mn2+ dependent 1B; PRKAA/AMPKα: protein kinase AMP-activated catalytic subunit alpha; PtdIns: phosphatidylinositol; PtdIns3P: phosphatidylinositol-3-phosphate; RASAL2: RAS protein activator like 2; RasGAPs: RasGTPase activating proteins; SQSTM1/p62: sequestosome 1; TNBC: triple-negative breast cancer. [ABSTRACT FROM AUTHOR]

Cervical cancer (CC) is a common gynecological malignancy and represents a major global health challenge. Chemotherapeutic agents are commonly applied in treatment of CC, while along various adverse effects and chemotherapy resistance. As an iridoid glycoside compound, gentiopicroside (GPS) possesses the characteristic of the better availability and lower toxicity effect on cancer treatment. In the present study, we investigated that GPS exhibited the anticancer effect on HeLa cells through the inhibition of cell growth, induced apoptosis, cycle arrest, and suppressed migration. Furthermore, the possible mechanism or the targets of GPS was also clarified. The results revealed that GPS exerted an anti-proliferation effect in a dose- and time-dependent manner in HeLa cells, in contrast, with the less inhibiting proliferation effects on normal cell line (HUVEC). Moreover, GPS arrested cells at G2/M phase and induced apoptosis through mitochondrial apoptotic pathway. More significantly, GPS dramatically inhibited the migration of HeLa cells and regulated the matrix metalloproteinase expression through the MAPK and Akt signaling pathways, of which MAPK1 was an underlying target in GPS against HeLa cells. [ABSTRACT FROM AUTHOR]

RNA modifications are dynamic chemical entities that expand the RNA lexicon and regulate RNA fate. The most abundant modification present in mRNAs, N6-methyladenosine (m6A), has been implicated in neurogenesis and memory formation. However, whether additional RNA modifications may be playing a role in neuronal functions and in response to environmental queues is largely unknown. Here we characterize the biochemical function and cellular dynamics of two human RNA methyltransferases previously associated with neurological dysfunction, TRMT1 and its homolog, TRMT1-like (TRMT1L). Using a combination of next-generation sequencing, LC-MS/MS, patient-derived cell lines and knockout mouse models, we confirm the previously reported dimethylguanosine (m2,2G) activity of TRMT1 in tRNAs, as well as reveal that TRMT1L, whose activity was unknown, is responsible for methylating a subset of cytosolic tRNAAla(AGC) isodecoders at position 26. Using a cellular in vitro model that mimics neuronal activation and long term potentiation, we find that both TRMT1 and TRMT1L change their subcellular localization upon neuronal activation. Specifically, we observe a major subcellular relocalization from mitochondria and other cytoplasmic domains (TRMT1) and nucleoli (TRMT1L) to different small punctate compartments in the nucleus, which are as yet uncharacterized. This phenomenon does not occur upon heat shock, suggesting that the relocalization of TRMT1 and TRMT1L is not a general reaction to stress, but rather a specific response to neuronal activation. Our results suggest that subcellular relocalization of RNA modification enzymes may play a role in neuronal plasticity and transmission of information, presumably by addressing new targets. [ABSTRACT FROM AUTHOR]

Macroautophagy/autophagy, a cellular process that sequesters and breaks down cellular components in the lysosome/vacuole, is important in various events where cell composition undergoes changes. Broadly, autophagy is involved in T cell regulation including maintaining cell homeostasis. One process where a cell alters its composition is in the activation of helper T cells in the immune system. When helper (CD4+) T cells are activated by antigens, they both grow and alter their cellular components to become effector T cells. Autophagy is the process that facilitates the breakdown of these cellular components and is therefore hypothesized to have a role in CD4+ T cell activation. Previous research has concluded that CD4+ T cell activation induces autophagy, providing an avenue for further research aimed at examining the ways in which this induced autophagy affects CD4+ T cell proliferation and function. Toward this end, Zhou et al. researched the autophagosomal cargo present within CD4+ T cells and the impact this cargo has on CD4+ T cell proliferation. [ABSTRACT FROM AUTHOR]