Transduction Processes Research Articles

Advances in bioimaging techniques for studying cellular mechanics

Recent bioimaging advances have greatly aided cellular mechanics research. These advances have given researchers a new understanding of cell structure and function. Thus, these approaches have great optical coherence tomography (OCT) and temporal resolution, helping researchers understand previously inaccessible mechanical cell functions. The biggest drawback of all current techniques is their low resolutions, poor specificity, and inability to investigate cellular mechanics in complicated biological contexts in real-time. Introducing Cellular Mechanics using Bioimaging Techniques (CM-BT) will solve these difficulties. Combining advanced imaging modalities with unique computational methodologies, CM-BT may improve understanding of cellular mechanics. These methods improve resolution, specificity, and real-time performance. This technology uses super-resolution microscopy, fluorescence lifetime imaging, and machine learning-based image processing to reveal local mechanical properties and intercellular interactions. The results indicate that CM-BT improved temporal and spatial resolutions. This allowed researchers to view cellular dynamics with unparalleled precision and clarity before the inquiry. This technique also provides fresh information on mecha no transduction processes, including migration and mitosis, which increases understanding of cellular pathology.

Transcriptome signature for multiple biotic and abiotic stress in barley (Hordeum vulgare L.) identifies using machine learning approach

Barley (Hordeum vulgare L.) is exposed to various biotic and abiotic stresses, making it crucial to fully understand the gene signatures that respond to stress. This study utilizes machine learning to analyze transcriptomic data from 515 RNA-seq profiles across 18 independent studies, covering eleven abiotic and three biotic stress types. Through meticulous data preprocessing, including quality assessment and batch effect correction, we have identified 4,311 genes for further analysis. Feature selection was performed using five weighting algorithms, resulting in the prioritization of 400 core genes. Machine learning models, specifically Random Forest and C4.5, were optimized and evaluated using a 10-fold cross-validation approach. The C4.5 algorithm demonstrated superior accuracy in predicting stress-responsive signatures. Key genes, such as bHLH119 and E3 ubiquitin protein ligase DRIP2, were identified as potential biomarkers. Functional enrichment analysis, conducted through protein-protein interaction networks and Gene Ontology/KEGG pathway analysis, has revealed significant involvement in lipid biosynthesis, signal transduction, and defense response processes. These findings highlight the crucial roles of the identified biomarkers genes in barley's resilience to stress and provide potential targets for genetic improvement. Future research should focus on validating these biomarkers in different barley cultivars and under field conditions to enhance crop resilience against stressors.

Unraveling GPCRs Allosteric Modulation. Cannabinoid 1 Receptor as a Case Study.

G-protein-coupled receptors (GPCRs) constitute one of the most prominent families of integral membrane receptor proteins that mediate most transmembrane signaling processes. Malfunction of these signal transduction processes is one of the underlying causes of many human pathologies (Parkinson's, Huntington's, heart diseases, etc), provoking that GPCRs are the largest family of druggable proteins. However, these receptors have been targeted traditionally by orthosteric ligands, which usually causes side effects due to the simultaneous targeting of homologous receptor subtypes. Allosteric modulation offers a promising alternative approach to circumvent this problematic and, thus, comprehending its details is a most important task. Here we use the Cannabinoid type-1 receptor (CB1R) in trying to shed light on this issue, focusing on positive allosteric modulation. This is done by using the protein-dipole Langevin-dipole (PDLD) within the linear response approximation (LRA) framework (PDLD/S-2000) along with our coarse-grained (CG) model of membrane proteins to evaluate the dissociation constants (KBs) and cooperativity factors (αs) for a diverse series of CB1R positive allosteric modulators belonging to the 2-phenylindole structural class, considering CP55940 as an agonist. The agreement with the experimental data evinces that significantly populated allosteric modulator:CB1R and allosteric modulator:CP55940:CB1R complexes have been identified and characterized successfully. Analyzing them, it has been determined that CB1R positive allosteric modulation lies in an outwards displacement of transmembrane α helix (TM) 4 extracellular end and in the regulation of the range of motion of a compound TM7 movement for binary and ternary complexes, respectively. In this respect, we achieved a better comprehension of the molecular architecture of CB1R positive allosteric site, identifying Lys1923.28 and Gly1943.30 as key residues regarding electrostatic interactions inside this cavity, and to rationalize (at both structural and molecular level) the exhibited stereoselectivity in relation to positive allosteric modulation activity by considered CB1R allosteric modulators. Additionally, putative/postulated allosteric binding sites have been screened successfully, identifying the real CB1R positive allosteric site, and most structure-activity relationship (SAR) studies of CB1R 2-phenylindole allosteric modulators have been rationalized. All these findings point out towards the predictive value of the methodology used in the current work, which can be applied to other biophysical systems of interest. The results presented in this study contribute significantly to understand GPCRs allosteric modulation and, hopefully, will encourage a more thorough exploration of the topic.

MFPSP: Identification of fungal species-specific phosphorylation site using offspring competition-based genetic algorithm.

Protein phosphorylation is essential in various signal transduction and cellular processes. To date, most tools are designed for model organisms, but only a handful of methods are suitable for predicting task in fungal species, and their performance still leaves much to be desired. In this study, a novel tool called MFPSP is developed for phosphorylation site prediction in multi-fungal species. The amino acids sequence features were derived from physicochemical and distributed information, and an offspring competition-based genetic algorithm was applied for choosing the most effective feature subset. The comparison results shown that MFPSP achieves a more advanced and balanced performance to several state-of-the-art available toolkits. Feature contribution and interaction exploration indicating the proposed model is efficient in uncovering concealed patterns within sequence. We anticipate MFPSP to serve as a valuable bioinformatics tool and benefiting practical experiments by pre-screening potential phosphorylation sites and enhancing our functional understanding of phosphorylation modifications in fungi. The source code and datasets are accessible at https://github.com/AI4HKB/MFPSP/.

GWAS-Based Prediction of Genes Regulating the Weight of Mobilized Reserved Seeds in Sweet Corn

Seed reserve mobilization is a crucial physiological process during seed germination. Enhancing the reserve mobilization in sweet corn is vital for seed germination and seedling growth. In this study, a genome-wide association analysis (GWAS) was conducted to predict candidate genes for regulating the weight of mobilized reserved seeds (WMRS) and kernel weight (KW) in sweet corn. GWAS was performed using the BLINK model with the maize 56K SNP chip. The results indicated that there was a positive correlation between the WMRS and KW, with coefficients of variation of 68.18% and 44.63%. Association analysis identified thirteen SNPs associated with two traits, and linkage disequilibrium analysis revealed that eight of these SNPs were in strong linkage. A total of 298 candidate genes were identified within the confidence interval, of which 79 were annotated. About 20 candidate genes were identified through the comparison of homologous genes in Arabidopsis. These genes were enriched in regulating ribosome biogenesis, signal transduction, hormone synthesis, and RNA degradation processes. This study provides important insights into the genetic mechanisms governing germination traits in sweet corn, aiding further research into the localization and cloning of genes involved in the mobilization of reserve materials.

Cyclosporin H Improves the Transduction of CD34+ Cells with an Anti-Sickling Globin Vector, a Possible Therapeutic Approach for Sickle Cell Disease.

Sickle cell disease (SCD) is a debilitating monogenic disease originating from mutations in the hemoglobin beta chain gene producing an abnormal hemoglobin HbS. The polymerization of HbS is responsible for the sickling of erythrocytes leading to anemia and vaso-occlusive events. Gene therapy is a promising treatment of SCD, and two different gene therapy drugs, using gene editing or gene transfer, have already reached the marketing stage. There is still a need to improve the efficacy of gene therapy in SCD, particularly when using anti-sickling beta-globin gene transfer strategies, which must outcompete the pathological HbS. One possibility is to increase transduction by inhibiting lentiviral restriction factors such as interferon-induced transmembrane proteins (IFITMs). This can be achieved by the addition of cyclosporin H (CsH) during the transduction process. This strategy was applied here in CD34+ hematopoietic progenitor and stem cells obtained from cord blood (CB). A first series of experiments with lentiviral vector coding for a green fluorescent protein (GFP) gene confirmed that the addition of CsH enhanced transgene expression levels and vector copy number per cell (VCN), while CD34+ cells remained viable and functional. Notably, the production of colony-forming cells (CFC) remained unaffected unless very high VCN values were reached. In a second step, CD34+ cells obtained from the CB of newborns with homozygous (n = 2) or heterozygous (n = 1) SCD mutations were transduced with the GLOBE-AS3 lentiviral vector coding for the HbAS3 anti-sickling beta globin. As with GFP, GLOBE-AS3 lentiviral transduction was clearly enhanced by CsH, leading to VCN > 2 and therapeutic levels of expression of the HbAS3. Moreover, the process did not affect the viability or functions of CFC. The combination of CB progenitors, the GLOBE-AS3 vector, and CsH is thus shown here to be a promising approach for the treatment of SCD.

Comparative transcriptome analysis of low- and high-latitude populations of Charybdis japonica under temperature stress

Global climate change has caused rapid temperature changes in marine environments. Understanding how marine organisms respond to temperature changes can help predict their richness of future biodiversity. In this study, we examined the gene expression levels and the difference in the pathways that are responsive to acute temperature stress in low- and high-latitude populations of the shore swimming crab, Charybdis japonica. The two populations of C. japonica were exposed to low- and high-temperature stresses (15°C and 28°C) and used for transcriptome sequencing. Genetic regulatory ability changes were compared to determine the diverse response of the two crab populations to temperature change. The gene expression levels and functional enrichment analysis showed that the low-latitude crab regulated more genes (938) that were mainly enriched in DNA replication and metabolic pathways, whereas the high-latitude crab regulated less genes (309) that were mainly enriched in genetic information processing at low-temperature stress. Furthermore, the low-latitude crab regulated less genes (33) that were mainly enriched in genetic information processing, whereas the high-latitude crab regulated more genes (280) that were mainly enriched in signal transduction and cellular process at high-temperature stress. These results implied that the low-latitude population was more resilient to high-temperature stress, while the high-latitude population was more resilient to low-temperature stress. This study enhances our understanding of how different geographic C. japonica populations respond to varying temperature environments in their living zone, which could be helpful for predicting future biodiversity trends of intertidal crustaceans under global climate change.

The Role of Fatty Acid Metabolism, the Related Potential Biomarkers, and Targeted Therapeutic Strategies in Gastrointestinal Cancers.

Gastrointestinal cancer has emerged as a significant global health concern due to its high incidence and mortality, limited effectiveness of early detection, suboptimal treatment outcomes, and poor prognosis. Metabolic reprogramming is a prominent feature of cancer, and fatty acid metabolism assumes a pivotal role in bridging glucose metabolism and lipid metabolism. Fatty acids play important roles in cellular structural composition, energy supply, signal transduction, and other lipid-related processes. Changes in the levels of fatty acid metabolite may indicate the malignant transformation of gastrointestinal cells, which have an impact on the prognosis of patients and can be used as a marker to monitor the efficacy of anticancer therapy. Therefore, targeting key enzymes involved in fatty acid metabolism, either as monotherapy or in combination with other agents, is a promising strategy for anticancer treatment. This article reviews the potential mechanisms of fatty acid metabolism disorders in the occurrence and development of gastrointestinal tumors, and summarizes the related potential biomarkers and anticancer strategies.

Mechanistic study of Nidus Vespae inhibiting gastric cancer in vitro through the JAK2/STAT3 signaling pathway

Ethnopharmacological relevanceNidus Vespae, an animal-derived traditional Chinese medicine, has a long-standing history in treating inflammatory conditions and tumor-related diseases. Notably, Nidus Vespae decoction (NVD) has been shown to inhibit the proliferation of gastric cancer cells, although the underlying mechanisms remain unclear. ObjectiveThis study aimed to elucidate the efficacy and mechanisms by which NVD exerts its therapeutic effects on gastric cancer. Materials and methodsWe employed the Cell Counting Kit-8 (CCK-8) assay to assess the impact of NVD on gastric cancer cell proliferation, while flow cytometry was utilized to evaluate cell cycle arrest and apoptosis. Differentially expressed proteins (DEPs) were identified by proteomics analysis, which were further analyzed through Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Protein-protein interaction (PPI) analysis was conducted to identify the hub genes. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were conducted to assess mRNA and protein levels related to apoptosis, cell cycle regulation, and the JAK2/STAT3 pathway. Rescue experiments with Colivelin TFA confirmed the role of NVD in inhibiting gastric cancer cell proliferation. UPLC-HRMS and HS-SPME-GC-MS technologies were performed to analyze the composition of NVD, and the bioinformatics tool called BATMAN-TCM database was used for functional analyses. ResultsOur results demonstrated that NVD significantly hindered the proliferation of gastric cancer cells, initiated programmed cell death, and induced cell cycle arrest in G2/M or G0/G1 phases in various gastric carcinoma cells in vitro. The identified DEPs were involved in several cancer-related pathways and signal transduction processes, notably the JAK-STAT receptor signaling pathway. NVD was found to down-regulate the JAK2/STAT3 signaling cascade, and reactivation of STAT3 diminished its anti-gastric cancer effects. Finally, the ingredient-target-disease network analysis also verified the anti-tumor effect of NVD. ConclusionThis study highlights the potential of Nidus Vespae as a therapeutic agent for gastric cancer, providing insights into its molecular mechanisms of action.

Interplay Between the Circadian Clock and Sirtuins.

The circadian clock is an autonomous timekeeping system evolved by organisms to adapt to external changes, regulating a variety of important physiological and behavioral processes. Recent studies have shown that the sirtuin family of histone deacetylases is involved in regulating the expression of clock genes and plays an important role in maintaining the normal rhythm of clock gene expression and behavior. Moreover, sirtuins are regulated directly or indirectly by the circadian clock system. The mutual regulation between the circadian clock and sirtuins is likely involved in a variety of signal transduction and metabolism processes. In this review, we discuss the molecular mechanisms and research progress on the intertwined relationship between the circadian clock and sirtuins, mainly in mammals, highlighting sirtuins as molecular links between metabolic control and circadian rhythms and offering our perspectives on future developments in the field.

Mechanistic effects of lipid binding pockets within soluble signaling proteins: Lessons from acyl-CoA-binding and START-domain-containing proteins.

While lipids serve as important energy reserves, metabolites, and cellular constituents in all forms of life, these macromolecules also function as unique carriers of information in plant communication given their diverse chemical structures. The signal transduction process involves a sophisticated interplay between messengers, receptors, signal transducers, and downstream effectors. Over the years, an array of plant signaling proteins have been identified for their crucial roles in perceiving lipid signals. However, the mechanistic effects of lipid binding on protein functions remain largely elusive. Recent literature has presented numerous fascinating models that illustrate the significance of protein-lipid interactions in mediating signaling responses. This review focuses on the category of lipophilic signaling proteins that encompass a hydrophobic binding pocket located outside of cellular membranes and provides an update on the lessons learned from two of these structures, namely the acyl-CoA-binding and START domains. It begins with a brief overview of the latest advances in understanding the functions of the two protein families in plant communication. The second part highlights five functional mechanisms of lipid ligands in concert with their target signaling proteins.

Microarray analysis of microRNA profiles for assessing the therapeutic effects of sodium thiosulfate on end-stage renal disease combined with coronary artery calcification.

Coronary artery calcification (CAC) is a common complication in patients with end-stage renal disease (ESRD), which causes of increased cardiovascular mortality in maintenance hemodialysis patients. This study examined how sodium thiosulfate (STS) treatment affects the microRNA (miRNA) expression profiles of ESRD patients combined with CAC. A total of 18 patients with ESRD complicated with CAC were assigned to a control group that received conservative treatment or a test group that received STS treatment. The 2 groups were then sub-divided into a CGBT group (control group before treatment), TGBT group (test group before treatment), CGAT group (control group after treatment), and TGAT group (test group after treatment). Samples of peripheral venous blood were collected for analysis of biochemical indexes (hs-CRP, ALB, CHO, TG, Ca, P, BUN, Cr, bALP, iPTH, and FGF23) and used to screen for differentially expressed miRNAs that were displayed by hierarchical clustering and in a volcano plot. The functional roles of miRNA target genes were analyzed by Gene Ontology and Kyoto Encycolopedia of Genes and Genomes pathway analyses. Several miRNAs in serum samples were identified using quantitative real time PCR. STS treatment did not significantly change the biochemical indexes. A microarray analysis identified 67 miRNAs that were differentially expressed in the TGAT group vs. the TGBT group, and 28 -miRNAs that were differentially expressed in the CGAT group vs. the CGBT group. The miRNA target genes were associated with signal transduction, transcriptional regulation, cytoplasm and protein binding processes, the MAPK signaling pathway, PI3K-Akt signaling pathway, and various pathways in cancer. Validation experiments confirmed the suppressive effect of STS treatment on miR-337-5p/miR-409-5p expression and the promotive effect of STS on miR-376a-3p expression. MiR-337-5p/miR-409-5p/miR-376a-3p might be key regulators involved with the therapeutic effects of STS treatment in ESRD patients associated with arterial calcification.

The advancement of cuproptosis in hematological tumors

Cuproptosis is a type of independent cell death form, that differs from apoptosis, necroptosis and ferroptosis. It is mediated by Copper (Cu), and mainly affects the lipoylation of proteases in the mitochondrial tricarboxylic acid (TCA) cycle and exhibits cytotoxicity through oligomerization; however, its specific mechanism, signal transduction process and regulation mode are still not clear. Mitochondria affect the sensitivity of cells to copper toxicity and play a central role in the occurrence and development of copper-related death. In recent years, though hematological tumors have achieved better remission through targeted therapy and immunotherapy, they are associated with high recurrence rates and poor prognoses. It is therefore imperative to find better prognostic indicators and new treatment ideas. This paper summarizes the interaction between Cu and mitochondria in the development of tumors and provides ideas for further exploration of the mechanism of copper death and coping with hematological tumors.

Genome-Wide Identification and Expression Analysis of the MADS-Box Gene Family in Cassava (Manihot esculenta)

The MADS-box gene family constitutes a vital group of transcription factors that play significant roles in regulating plant growth, development, and signal transduction processes. However, research on the MADS-box genes in cassava (Manihot esculenta) has been relatively limited. To gain deeper insights into the functions of the MADS-box genes in cassava development, in this study, we undertook a comprehensive genome-wide identification of the MADS-box gene family in cassava. We identified a total of 86 MADS-box genes with complete domains in the cassava genome, designated as MeMADS01 to MeMADS86. Through bioinformatic analyses, we investigated the basic physicochemical properties, conserved motifs, chromosomal locations, and phylogenetic relationships of the cassava MADS-box genes. The MADS-box gene family of cassava exhibited conservation, as well as species-specific characteristics, with intron loss being a predominant mode of evolution for the MADS-box genes. Expression pattern variations in the MeMADS genes across different tissues offer insights into their potential functions. Time-ordered gene co-expression network (TO-GCN), transcriptome data, and RT-qPCR analysis suggested the responsiveness of the MADS-box genes to drought stress. Meanwhile, MeMADS12 might be involved in regulating flowering under drought conditions via an ABA (abscisic acid)-dependent pathway. These findings provide valuable resources for a deeper understanding of the biological roles of the MADS-box genes in cassava.

Analysis of the plant hormone expression profile during somatic embryogenesis induction in teak (Tectona grandis).

Plant somatic embryogenesis (SE) is an efficient regeneration system for propagation. It involves the regulation of a complex molecular regulatory network encompassing endogenous hormone synthesis, metabolism, and signal transduction processes, induced through exogenous plant growth regulators. Previous studies have focused primarily on traditional propagation methods for Tectona grandis, but there is limited knowledge on SE and its hormonal regulatory mechanisms. In our study, different SE stages, including the nonembryogenic callus (NEC), embryogenic callus (EC), and globular and heart-shaped embryo (E-SEs) stages, were induced in teak cotyledons incubated on MS medium supplemented with 0.1 mg/L thidiazuron (TDZ). Morphological and histological observations indicated that EC primarily originates from the development of embryogenic cell clusters. During SE induction, the levels of six classes of endogenous hormones, IAA, CTK, ETH, ABA, SA, and JA, changed significantly. Transcriptome analysis revealed that endogenous hormones participate in SE induction in teak through various biological processes, such as biosynthesis, metabolism, and signal transduction pathways. We found that IAA biosynthesis primarily occurs through the IAM pathway during these three stages. The ETH receptor kinase gene SERF1 exhibited the highest expression levels in E-SEs. The ABA-, SA-, and JA-related signal transduction genes ABI3, NPR1, and JAZ exhibited no differential expression during different stages. Moreover, key encoding genes of SE regulators, including WUS, WOX and SERK, were differentially expressed during SE. In conclusion, this study offers insights into the roles of endogenous hormones and their interactions during SE induction.

Hormonal signaling regulates photosynthetic function of alfalfa (Medicago sativa L.) under NaHCO3 stress

The physiological and molecular mechanisms underlying salt-alkali tolerance in Medicago sativa are of significant importance for the development of animal husbandry on salt-alkali lands and the restoration of vegetation in such areas. This study utilized salt-alkali tolerance Medicago sativa 'Zhaodong' (ZD) and salt-alkali sensitive variety M. sativa 'Zhongmu No.1′ (ZM) as materials. Physiological analyses, transcriptomic sequencing, and hormone-targeted metabolomics techniques were employed to investigate the differential responses of the two alfalfa varieties to NaHCO3 stress in terms of morphology, photosynthetic functionality, and oxidative damage indicators. Additionally, weighted gene co-expression network analysis (WGCNA) was utilized to elucidate key mechanisms underlying salt-alkali tolerance in alfalfa. The results indicate that NaHCO3 stress leads to photosynthetic inhibition and oxidative damage in alfalfa leaves. Under NaHCO3 stress, PSI in alfalfa leaves exhibits higher stability compared to PSII. The salt-alkali tolerance alfalfa variety ZD demonstrates stronger tolerance compared to the salt-alkali sensitive variety ZM. Furthermore, differentially expressed genes (DEGs) between the two varieties under NaHCO3 stress are primarily enriched in KEGG pathways such as chlorophyll synthesis, photosynthesis, carbon fixation, and plant hormone synthesis and signaling. Weighted gene co-expression network analysis (WGCNA) was conducted based on physiological and transcriptomic data. Most differentially expressed genes (DEGs) in the top two modules with the highest correlation to physiological indicators such as photosynthesis are enriched in hormone synthesis and signal transduction pathways. Additionally, key transcription factors involved in hormone signal transduction were identified within these modules, such as MYC2 and ABI5, which regulate jasmonic acid (JA) and abscisic acid (ABA) signaling, respectively. These findings suggest that plant hormone signaling may play a critical role in regulating salt-alkali tolerance in alfalfa. Further analysis was conducted on plant hormone levels and gene expression involved in biosynthesis and signal transduction processes. The results indicate that NaHCO3 stress leads to significant accumulation of ABA and JA content in alfalfa leaves. The biosynthesis and signal transduction pathways of ABA and JA are activated under NaHCO3 stress. Additionally, the salt-alkali tolerance alfalfa variety ZD exhibits a more sensitive response to ABA and JA signals compared to ZM. Salicylic acid (SA) shows a positive response to NaHCO3 stress only in the ZD variety, which may be one of the key reasons for its stronger salt-alkali tolerance. Under NaHCO3 stress, overall growth-promoting hormones (IAA, GA, CK) are downregulated in ZD but upregulated in ZM, indicating that the salt-alkali tolerance alfalfa variety ZD mainly regulates the balance between growth and resistance by modulating the ratio of growth-promoting and stress-related hormones in response to NaHCO3 stress. This study reveals that hormone signaling plays a key role in regulating the photosynthetic function of alfalfa in response to salt-alkali stress, which provides theoretical basis and clues for the molecular breeding of alfalfa for salt-alkali tolerance.

RACK1 inhibits ferroptosis of cervical cancer by enhancing SLC7A11 core-fucosylation.

Receiver for Activated C Kinase 1 (RACK1) is a highly conserved scaffold protein that can assemble multiple kinases and proteins together to form complexes, thereby regulating signal transduction process and various cellular biological processes, including cell cycle regulation, differentiation, and immune response. However, the function and mechanism of RACK1 in cervical cancer remain incompletely understood. Here we identified that RACK1 could significantly suppress cell ferroptosis in cervical cancer cells. Mechanistically, RACK1 increased the expression of FUT8 by inhibiting miR-1275, which in turn promoted the FUT8-catalyzed core-fucosylation of cystine/glutamate antiporter SLC7A11, thereby inhibiting SLC7A11 degradation and cell ferroptosis. Our data highlight the role of RACK1 in cervical cancer progression and its suppression of ferroptosis via the RACK1/miR-1275/FUT8/SLC7A11 axis, suggesting that inhibiting this pathway may be a promising therapeutic approach for patients with cervical cancer.

Interplay between the Redox System and Renal Tubular Transport.

The kidney plays a critical role in maintaining the homeostasis of body fluid by filtration of metabolic wastes and reabsorption of nutrients. Due to the overload, a vast of energy is required through aerobic metabolism, which inevitably leads to the generation of reactive oxygen species (ROS) in the kidney. Under unstressed conditions, ROS are counteracted by antioxidant systems and maintained at low levels, which are involved in signal transduction and physiological processes. Accumulating evidence indicates that the reduction-oxidation (redox) system interacts with renal tubular transport. Redox imbalance or dysfunction of tubular transport leads to renal disease. Here, we discuss the ROS and antioxidant systems in the kidney and outline the metabolic dysfunction that is a common feature of renal disease. Importantly, we describe the key molecules involved in renal tubular transport and their relationship to the redox system and, finally, summarize the impact of their dysregulation on the pathogenesis and progression of acute and chronic kidney disease.

Mechanisms of mechanical stimulation in the development of respiratory system diseases.

During respiration, mechanical stress can initiate biological responses that impact the respiratory system. Mechanical stress plays a crucial role in the development of the respiratory system. However, pathological mechanical stress can impact the onset and progression of respiratory diseases by influencing the extracellular matrix and cell transduction processes. In this article, we explore the mechanisms by which mechanical forces communicate with and influence cells. We outline the basic knowledge of respiratory mechanics, elucidating the important role of mechanical stimulation in influencing respiratory system development and differentiation from a microscopic perspective. We also explore the potential mechanisms of mechanical transduction in the pathogenesis and development of respiratory diseases such as asthma, lung injury, pulmonary fibrosis, and lung cancer. Finally, we look forward to new research directions in cellular mechanotransduction, aiming to provide fresh insights for future therapeutic research on respiratory diseases.

Optimization of Cellular Transduction by the HIV-Based Pseudovirus Platform with Pan-Coronavirus Spike Proteins.

Over the past three years, new SARS-CoV-2 variants have continuously emerged, evolving to a point where an immune response against the original vaccine no longer provided optimal protection against these new strains. During this time, high-throughput neutralization assays based on pseudoviruses have become a valuable tool for assessing the efficacy of new vaccines, screening updated vaccine candidates against emerging variants, and testing the efficacy of new therapeutics such as monoclonal antibodies. Lentiviral vectors derived from HIV-1 are popular for developing pseudo and chimeric viruses due to their ease of use, stability, and long-term transgene expression. However, the HIV-based platform has lower transduction rates for pseudotyping coronavirus spike proteins than other pseudovirus platforms, necessitating more optimized methods. As the SARS-CoV-2 virus evolved, we produced over 18 variants of the spike protein for pseudotyping with an HIV-based vector, optimizing experimental parameters for their production and transduction. In this article, we present key parameters that were assessed to improve such technology, including (a) the timing and method of collection of pseudovirus supernatant; (b) the timing of host cell transduction; (c) cell culture media replenishment after pseudovirus adsorption; and (d) the centrifugation (spinoculation) parameters of the host cell+ pseudovirus mix, towards improved transduction. Additionally, we found that, for some pseudoviruses, the addition of a cationic polymer (polybrene) to the culture medium improved the transduction process. These findings were applicable across variant spike pseudoviruses that include not only SARS-CoV-2 variants, but also SARS, MERS, Alpha Coronavirus (NL-63), and bat-like coronaviruses. In summary, we present improvements in transduction efficiency, which can broaden the dynamic range of the pseudovirus titration and neutralization assays.