Cellular Communication Research Articles

Endocannabinoids regulate enteric neuron-glia networks and visceral hypersensitivity following inflammation through a glial-dependent mechanism.

Acute gastrointestinal (GI) inflammation induces neuroplasticity that produces long-lasting changes in gut motor function and pain. The endocannabinoid system is an attractive target to correct pain and dysmotility, but how inflammation changes endocannabinoid control over cellular communication in enteric neurocircuits is not understood. Enteric glia modulate gut neurons that control motility and pain and express monoacylglycerol lipase (MAGL) which controls endocannabinoid availability. We used a combination of in situ calcium imaging, chemogenetics, and selective drugs to study how endocannabinoid mechanisms affect glial responses and subsequent enteric neuron activity in health and following colitis in Wnt1Cre;GCaMP5g-tdT;GFAP::hM3Dq mice. Trpv1Cre;GCaMP5gtdT mice were used to study nociceptor sensitivity and Sox10CreERT2;Mgllf/f mice were used to test the role of glial MAGL in visceral pain. The data show that endocannabinoid signaling regulates neuro-glial signaling in gut neurocircuits in a sexually dimorphic manner. Inhibiting MAGL in healthy samples decreased glial responsiveness but this effect was lost in females following colitis and converted to an excitatory effect in males. Manipulating CB1 and CB2 receptors revealed further sex differences amongst neuro-glia signaling that were impacted following inflammation. Inflammation increased gut nociceptor sensitivity in both sexes but only females exhibited visceral hypersensitivity in vivo. Blocking MAGL normalized nociceptor responses in vitro and deleting glial Mgll in vivo rescued visceral hypersensitivity in females. These results show that sex and inflammation impact endocannabinoid mechanisms that regulate intercellular enteric glia-neuron communication. Further, targeting glial MAGL could provide therapeutic benefits for visceral nociception in a sex-dependent manner.

5G Analysis Using Software Applications

Recently, 5G connection is widely used for mobile communication. The 5G technology is increasingly implemented in Malaysia country and in the big towns. There are many researches have been done to test and improve the connection. For the research analysis, Net Analyzer, nPerf, Meteor and speedtest applications that can measure parameters related to cellular communication have been used as a measurement tool. As a conclusion, internet and mobile connection shows that the performances are good for the users.

Cellular network measurements can unravel spatiotemporal properties of bird movement to enhance basic and applied knowledge globally

Abstract A major problem in studying bird movement in many countries is data scarcity, precluding information about the spatial and temporal properties of avian distribution and dynamics as well as their consequences for human lives. We address this problem by proposing an innovative approach based on the relation between counts of signal attenuation of wireless communication to the presence of birds across or near wireless links of cellular backhaul networks. Wireless point-to-point communication links, on either ground level or earth-satellite links, cover the globe. We statistically relate between signal attenuation in terrestrial Commercial Microwave Links (CMLs) and bird migration. Because modern communication systems measure and often log signal levels routinely, we propose using existing signal level measurements of cellular and other wireless communication systems around the world as sensors for monitoring of bird movement. Using actual measurements from operational CMLs, we show that the daily cycle of signal attenuation during bird migration periods matched that of waterbird migration traffic rate recorded by nearby bird radar. This demonstrates the potential of the proposed method for opportunistic bird movement monitoring by CMLs across the globe, with no additional hardware installation, maintenance or communication costs.

(Invited) Cardiac Engineering: Optical Mapping in Cellular Communication

Microfluidic platforms have emerged as valuable tools for replicating the adverse effects of chemotherapy drugs on cardiac and non-cardiac cells in vitro. However, these systems currently fall short of comprehensively capturing the intricate nature of human responses to chemotherapy, necessitating further validation to enhance model accuracy. While innovative chip systems provide insightful means for screening cardiac toxicity, they encounter challenges in addressing individual variations in drug responses and the influence of patient-specific factors.A novel cardiac chip incorporating intracellular electrophysiological techniques was developed to monitor acute hypoxia-induced responses in cardiac cells. Despite its promising potential, the model exhibits limitations inherent to its simplified two-dimensional microfluidic system, warranting additional validation and optimization efforts to enhance physiological relevance and facilitate applications in clinical translation.Moreover, previous research has proposed the formation of functional connections between human neurons and myocardial cells in a microfluidic chip. However, this study primarily focused on one-way connections between neurons and myocardial cells, overlooking the complexities of bidirectional neuro-muscular connections. Consequently, further research is imperative to deepen our understanding of the intricate interactions between neurons and myocardial cells.Optical mapping techniques assessed transmembrane voltage, mitochondrial activity, and calcium signals during electric pacing. These comprehensive assessments aim to advance our understanding of cardiac electrophysiology under drug exposure, providing crucial insights into the intricate responses of cardiac cells to chemotherapy. This research has significant implications for enhancing our understanding of cardiac safety in the context of chemotherapy.

Antioxidant Potential of Exosomes in Animal Nutrition.

This review delves into the advantages of exosomes as novel antioxidants in animal nutrition and their potential for regulating oxidative stress. Although traditional nutritional approaches promote oxidative stress defense systems in mammalian animals, several issues remain to be solved, such as low bioavailability, targeted tissue efficiency, and high-dose by-effect. As an important candidate offering regulation opportunities concerned with cellular communication, disease prevention, and physiology regulation in multiple biological systems, the potential of exosomes in mediating redox status in biological systems has not been well described. A previously reported relationship between redox system regulation and circulating exosomes suggested exosomes as a fundamental candidate for both a regulator and biomarker for a redox system. Herein, we review the effects of oxidative stress on exosomes in animals and the potential application of exosomes as antioxidants in animal nutrition. Then, we highlight the advantages of exosomes as redox regulators due to their higher bioavailability and physiological heterogeneity-targeted properties, providing a theoretical foundation and feed industry application. Therefore, exosomes have shown great potential as novel antioxidants in the field of animal nutrition. They can overcome the limitations of traditional antioxidants in terms of dosage and side effects, which will provide unprecedented opportunities in nutritional management and disease prevention, and may become a major breakthrough in the field of animal nutrition.

Factors affecting citizen intention toward AI acceptance and adoption: the moderating role of government regulations

Purpose This paper aims to explore factors impacting citizen intention toward artificial intelligence (AI) adoption, considering government regulation as a moderating variable. It focuses on the Palestinian Cellular Communications Sector in Gaza Strip, providing insights into the citizen-AI relationship dynamics. The research contributes to enhancing comprehension of AI technology from clients’ perspective. Design/methodology/approach To test the hypotheses, a questionnaire was used in an empirical study to collect primary data. In total, 347 Palestinian citizens responded to the survey. Findings The findings of this paper reveal that perceived usefulness, perceived ease of use, perceived risks, social influence, user experience and privacy and security concerns significantly influence citizen intention toward AI adoption. Furthermore, government regulations as a moderating variable strengthen the impact of perceived usefulness, perceived ease of use, perceived risks, social influence, user experience and privacy and security concerns on citizen intention toward AI acceptance and adoption. Thus, further research should explore specific domains and cultural contexts to gain a more comprehensive understanding of the factors shaping acceptance and adoption. Research limitations/implications The findings of the study should be understood in the context of their limitations. First, the study ignored cultural or domain-specific subtleties in favor of generic characteristics, which calls for more research in these particular circumstances. Second, relying on self-reported data might result in biases and limitations due to subjectivity in reporting, indicating the necessity for alternate data gathering methods and approaches in future research. Practical implications Policymakers, developers and organizations working to promote the acceptability and implementation of AI applications should consider the practical implications of this study’s results. To secure the long-term use of AI technologies in a responsible and user-centric way, policymakers should give priority to public education and awareness, user-centered design and ethical AI development techniques. They should also stimulate partnerships and create monitoring systems. Originality/value This paper investigates the originality of factors that influence citizen intention toward AI acceptance and adoption. It uniquely examines the moderating role of government regulations in shaping this intention. By addressing this novel aspect, the paper contributes to advancing our understanding of the complex dynamics surrounding citizen intentions toward AI applications.

Remediation Strategies of Xenobiotics in Urban Soils and Water: A Review

Xenobiotic substances are synthetic chemicals that are not native to a specificecological system yet have biological activity. Drugs, industrial chemicals, naturally occurring toxins, and environmental contaminants are all examples of xenobiotics. By disrupting or interfering with many cellular communication routes that control growth, development, and normal physiological function, xenobiotics can have a negative impact on human health. These chemicals are extremely poisonous in nature and can harm both lower and higher eukaryotes. These substances are persistent, allowing for bioaccumulation or biomagnification in the environment over time. They also find their way into food chains, where their concentrations are found to be high even in creatures that do not come into direct contact with xenobiotics. Industries regularly release xenobiotics into the environment, increasing the danger of human and other biota exposure. Despite the use of a variety of traditional and modern environment remediation technologies, some of them are unsuccessful at eliminating xenobiotics, while others are too expensive to use on a wide scale. Maize Stover and Rice Husk are abundantly generated across the world, making them attractive and cost-effective feedstocks for large scale biochar synthesis for environmental clean-up. Because virgin Maize Stover and Rice Husk biochar may not be successful in removing some xenobiotics, adding modifiers to MS/RH biochar can help to generate composite MS/RH biochar, which can aid to disinfect water and soil more effectively. Some microbes have the ability to partially or completely break down xenobiotic substances. The most dependable ways for degrading these chemicals are biological and non-biological remediation procedures. Bacterial biodegradation is a cost-effective approach for land filling and composting that employs both wild type and genetically engineered bacterial strains. Many non-biological approaches that are suited for xenobiotic degradation have been categorised under thermal and non-thermal procedures.

Narrow-Band, Band-Stop Filter Designs with Different Numbers of L-Resonators

Filters have an important place in RF and microwave engineering. Filtering certain frequencies is one of the most basic needs in receiver and transmitter systems. Today, microstrip filters are used in many areas of microwave engineering such as radar systems, cellular communications, test/measurement systems, wireless modems, radio and television receivers, and remote control systems. In these filter structures; high performance, low loss, small size, and low-cost requirements are sought. In this study, narrow-band, band-stop filter designs with different numbers of L-resonators at a frequency of 2.45 Hz were realized. The main goal of this study is to design filters with higher performance, lower return loss, and more compact and useful sizes. Thanks to these filter designs, undesirable signals are filtered and targeted signals are transmitted appropriately.

Design and Development of a Microcontroller-based Weight Measurement System for Liquid Agriculture Produce

This research presents the development of a microcontroller-based weight measurement system tailored for liquid agricultural products. The system addresses the limitations of traditional manual weighing methods by incorporating a load cell, ADC, microcontroller, LCD, and Bluetooth module. The load cell converts weight into an electrical signal, processed by the microcontroller and displayed on the LCD. Calibration ensures accurate weight measurements. The system's portability, cost-effectiveness, and user-friendly interface make it a promising solution for agricultural applications. Quantitative aspects include the precise weight measurement enabled by the load cell and ADC, with calibration enhancing accuracy. Qualitative aspects encompass the system's ease of use, portability, and potential for integration into broader agricultural management systems. Future enhancements include additional sensors for comprehensive product analysis, cellular communication for remote data transmission, and data logging capabilities. This research contributes to the automation and efficiency of liquid weight measurement in agriculture, potentially improving resource utilization and crop yields.

WVETT-Net: A Novel Hybrid Prediction Model for Wireless Network Traffic Based on Variational Mode Decomposition

Precise prediction of wireless communication network traffic is indispensable in the operational deployment of base station resources and improvement of the user experience. Cellular wireless network traffic has both spatial and temporal characteristics. The existing modeling algorithms have achieved good results in extracting the spatial features, but there are still deficiencies in the extraction models for the time dependencies. To resolve these problems, this paper proposes a novel hybrid neural network prediction model, called WVETT-Net. Firstly, variational mode decomposition (VMD) is used to preprocess network traffic, and the whale optimization algorithm (WOA) is used to select the optimal parameters for VMD. Secondly, the local and global features are extracted from each subsequence by a temporal convolutional network (TCN) and an improved Transformer network with a multi-head ProbSparse self-attention mechanism (Pe-Transformer), respectively. Finally, the extracted feature representation is enhanced by using an efficient channel attention (ECA) mechanism to achieve accurate wireless network traffic predictions. Experimental results on two wireless network traffic datasets show that the proposed model (WVETT-Net) outperforms the traditional single or combined models in wireless network traffic prediction.

Testing and Analysis of PIM Performance in a Passive DAS Network - Experimental Approach

Passive intermodulation (PIM) poses a significant challenge in telecommunication networks, with potentially severe impacts on network performance and signal integrity if not addressed during the initial deployment phase. This study investigates PIM levels within a passive distributed antenna system (DAS) network for cellular mobile radio communication across multiple floors of a building. The network comprises coaxial cables, connectors, splitters, combiners, and antennas structured in a systematic plan. This work used the experimental method to test for PIM in the network used for this investigation. Designed as a multicarrier system, it handles RF signals across frequencies of 700/850MHz, 1900MHz, 2100MHz, and 2600MHz. On-site PIM testing was conducted during the network deployment phase to analyze the behavior of high-power RF signals. Utilizing Kaelus iQA-1921C and iQA 850C series PIM analyzers, tests were conducted following known industry codes and standards. High RF power was preset to 43dBm for full band, 35dBm for high bands, and 25dBm for low band. The test equipment was calibrated on high PIM load and low PIM load. Test points were selected at both vertical and horizontal subsystem cabling structures, focusing on riser cables. The standard baseline performance PIM levels was set to -150dBc. The analysis focused on examining the characteristics of PIM signals captured via time-domain PIM traces, investigating the impact of altering the frequency of the two-tone signal on the IM3 frequency component, and highlighting the importance of selecting an appropriate frequency for the two-tone signal that is not positioned near the edges. Results were based on pass or fail test, and resolution measures were taken to mitigate interference.

Novel extracellular lipase gene Lip1728 influences nutrient-dependent performance bacterial quorum sensing of Burkholderia pyrrocinia WZ10-3

Quorum sensing (QS) is a cellular communication mechanism in which bacteria secrete and recognize signaling molecules to regulate group behavior. Lipases provide energy for bacterial cell growth but it is unknown whether they influence nutrient-dependent QS by hydrolyzing substrate. A high-yield lipase-producing strain, Burkholderia pyrrocinia WZ10–3, was previously identified in our laboratory, but the composition of its crude enzymes was not elucidated. Here, we identified a key extracellular lipase, Lip1728, in WZ10–3, which accounts for 99 % of the extracellular lipase activity. Lip1728 prefers to hydrolyze triglycerides at sn-1,3 positions, with pNP-C16 being its optimal substrate. Lip1728 exhibited activity at pH 5.0–10.0 and regardless of the presence of metal ions. It had strong resistance to sodium dodecyl sulfate and short-chain alcohols and was activated by phenylmethanesulfonylfluoride (PMSF). Lip1728 knockout significantly affected lipid metabolism and biofilm formation in the presence of olive oil. Finally, oleic acid, a hydrolysate of Lip1728, influenced the production of the signal molecule N-acyl homoserine lactone (AHL) and biofilm formation by downregulating the AHL synthetase gene pyrI. In conclusion, Lip1728, as a key extracellular lipase in B. pyrrocinia WZ10–3, exhibits superior properties that make it suitable for biodiesel production and plays a crucial role in QS.

An approach for user grouping and power allocation for downlink NOMA in a cellular wireless system

An approach for user grouping and power allocation for downlink NOMA in a cellular wireless system

Human mesenchymal stem cells-derived microvesicles increase oligodendrogenesis and neurogenesis of cultured adult neural stem cells

Mesenchymal stem cells (MSCs) are involved in tissue repair and anti-inflammatory activities and have shown promising therapeutic efficiency in different animal models of neurodegenerative disorders. Microvesicles (MVs), implicated in cellular communication, are secreted from MSCs and play a key role in determining the fate of cell differentiation. Our study examines the effect of human umbilical cord MSC-derived MVs (hUC-MSC MVs) on the proliferation and differentiation potential of adult neural stem cells (NSCs). Results showed that 0.2 μg MSC derived MVs significantly increased the viability of NSCs and their proliferation, as demonstrated by an increase in the number of neurospheres and their derived cells, compared to controls. In addition, all hUC-MSC MVs concentrations (0.1, 0.2 and 0.4 µg) induced the differentiation of NSCs toward precursors (Olig2 + ) and mature oligodendrocytes (MBP+). This increase in mature oligodendrocytes was inversely proportional to the dose of MVs. Moreover, hUC-MSC MVs induced the differentiation of NSCs into neurons (β-tubulin + ), in a dose-dependent manner, but had no effect on astrocytes (GFAP+). Furthermore, treatment of NSCs with hUC-MSC MVs (0.1 and 0.2 μg) significantly increased the expression levels of the proliferation marker Ki67 gene, compared to controls. Finally, hUC-MSC MVs (0.1 μg) significantly increased the expression level of Sox10 transcripts; but not Pax6 gene, demonstrating an increased NSC ability to differentiate into oligodendrocytes. In conclusion, our study showed that hUC-MSC MVs increased NSC proliferation in vitro and induced NSC differentiation into oligodendrocytes and neurons, but not astrocytes.

Exosomal MicroRNAs modulate the cognitive function in fasudil treated APPswe/PSEN1dE9 transgenic (APP/PS1) mice model of Alzheimer’s disease

Alzheimer’s disease (AD) is characterized by cognitive decline stemming from the accumulation of beta-amyloid (Aβ) plaques and the propagation of tau pathology through synapses. Exosomes, crucial mediators in neuronal development, maintenance, and intercellular communication, have gained attention in AD research. Yet, the molecular mechanisms involving exosomal miRNAs in AD remain elusive. In this study, we treated APPswe/PSEN1dE9 transgenic (APP/PS1) mice, a model for AD, with either vehicle (ADNS) or fasudil (ADF), while C57BL/6 (control) mice received vehicle (WT). Cognitive function was evaluated using the Y-maze test, and AD pathology was confirmed through immunostaining and western blot analysis of Aβ plaques and phosphorylated tau. Exosomal RNAs were extracted, sequenced, and analyzed from each mouse group. Our findings revealed that fasudil treatment improved cognitive function in AD mice, as evidenced by increased spontaneous alternation in the Y-maze test and reduced Aβ plaque load and phosphorylated tau protein expression in the hippocampus. Analysis of exosomal miRNAs identified three miRNAs (mmu-let-7i-5p, mmu-miR-19a-3p, mmu-miR-451a) common to both ADNS vs ADF and WT vs ADNS groups. Utilizing miRTarBase software, we predicted and analyzed target genes associated with these miRNAs. Gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of miRNA target genes indicated that mmu-miR-19a-3p and mmu-miR-451a are implicated in signal transduction, immune response, cellular communication, and nervous system pathways. Specifically, mmu-miR-19a-3p targeted genes involved in the sphingolipid signaling pathway, such as Pten and Tnf, while mmu-miR-451a targeted Nsmaf, Gnai3, and Akt3. Moreover, mmu-miR-451a targeted Myc in signaling pathways regulating the pluripotency of stem cells. In conclusion, fasudil treatment enhanced cognitive function by modulating exosomal MicroRNAs, particularly mmu-miR-451a and mmu-miR-19a-3p. These miRNAs hold promise as potential biomarkers and therapeutic targets for novel AD treatments.Graphical

Drug delivery based exosomes uptake pathways

Most cells secrete a material called extracellular vesicles (EVs), which play a crucial role in cellular communication. Exosomes are one of the most studied types of EVs. Recent research has shown the many functions and substrates of cellular exosomes. Multiple studies have shown the efficacy of exosomes in transporting a wide variety of cargo to their respective target cells. As a result, they are often utilized to transport medicaments to patients. Natural exosomes as well as exosomes modified with other compounds to enhance transport capabilities have been employed. In this article, we take a look at how different types of exosomes and modified exosomes may transport different types of cargo to their respective targets. Exosomes have a lot of potential as drug delivery vehicles for many synthetic compounds, proteins, nucleic acids, and gene repair specialists because they can stay in the body for a long time, are biocompatible, and can carry natural materials. A good way to put specific protein particles into exosomes is still not clear, though, and the exosomes can't be used in many situations yet. The determinants for exosome production, as well as ways for loading certain therapeutic molecules (proteins, nucleic acids, and small compounds), were covered in this paper. Further study and the development of therapeutic exosomes may both benefit from the information collected in this review.

Single-Cell Analysis of Debrided Diabetic Foot Ulcers Reveals Dysregulated Wound Healing Environment in Non-Hispanic Blacks

Diabetic foot ulcer (DFU) is a critical complication of diabetes, but the wound microenvironment and its healing process are not completely understood. In this study, we optimized single-cell profiling from sharp debrided ulcers. Our findings demonstrate that healing-DFUs were significantly enriched with distinct fibroblasts expressing genes related to inflammation (CHI3L1, IL6) and extracellular matrix remodeling (ASPN), validating our previous studies on surgically resected ulcers. The race-focused analysis depicted lower expression of key healing-associated genes such as CHIL3L1, MMP11, and SFRP4 in fibroblasts of non-Hispanic Black (NHB) patients compared to White patients. In cellular communication analysis, healing enriched fibroblasts of NHBs exhibited upregulation of signaling pathways such as WNT while those of White showed IGF and MK pathways upregulation. Our findings advocate race as a risk marker of DFU outcomes, likely reflecting underlying disparities in environmental exposures and access to care that profoundly influence healing markers. Using sharp debrided tissues for single-cell assays, this study highlights the need for in-depth investigations into dysregulated wound healing microenvironments of under-represented racial groups.

Matricellular protein CCN1 promotes collagen alignment and scar integrity after myocardial infarction

BackgroundMembers of the cellular communication network family (CCN) of matricellular proteins, like CCN1, have long been implicated in the regulation of cellular processes underlying wound healing, tissue fibrogenesis, and collagen dynamics. While many studies suggest antifibrotic actions for CCN1 in the adult heart through the promotion of myofibroblast senescence, they largely relied on exogenous supplementation strategies in in vivo models of cardiac injury where its expression is already induced—which may confound interpretation of its function in this process. The objective of this study was to interrogate the role of the endogenous protein on fibroblast function, collagen structural dynamics, and its associated impact on cardiac fibrosis after myocardial infarction (MI). Methods/resultsHere, we employed CCN1 loss-of-function methodologies, including both in vitro siRNA-mediated depletion and in vivo fibroblast-specific knockout mice to assess the role of the endogenous protein on cardiac fibroblast fibrotic signaling, and its involvement in acute scar formation after MI. In vitro depletion of CCN1 reduced cardiac fibroblast senescence and proliferation. Although depletion of CCN1 decreased the expression of collagen processing and stabilization enzymes (i.e., P4HA1, PLOD1, and PLOD2), it did not inhibit myofibroblast induction or type I collagen synthesis. Alone, fibroblast-specific removal of CCN1 did not negatively impact ventricular performance or myocardial collagen content but did contribute to disorganization of collagen fibrils and increased matrix compliance. Similarly, Ccn1 ablated animals subjected to MI showed no discernible alterations in cardiac structure or function one week after permanent coronary artery ligation, but exhibited marked increases in incidence of mortality and cardiac rupture. Consistent with our findings that CCN1 depletion does not assuage myofibroblast conversion or type I collagen synthesis in vitro, Ccn1 knockout animals revealed no measurable differences in collagen scar width or mass compared to controls; however, detailed structural analyses via SHG and TEM of scar regions revealed marked alterations in their scar collagen topography—exhibiting changes in numerous macro- and micro-level collagen architectural attributes. Specifically, Ccn1 knockout mice displayed heightened ECM structural complexity in post-MI scar regions, including diminished local alignment and heightened tortuosity of collagen fibers, as well as reduced organizational coherency, packing, and size of collagen fibrils. Associated with these changes in ECM topography with the loss of CCN1 were reductions in fibroblast-matrix interactions, as evidenced by reduced fibroblast nuclear and cellular deformation in vivo and reduced focal-adhesion formation in vitro; findings that ultimately suggest CCN1’s ability to influence fibroblast-led collagen alignment may in part be credited to its capacity to augment fibroblast-matrix interactions. ConclusionsThese findings underscore the pivotal role of endogenous CCN1 in the scar formation process occurring after MI, directing the appropriate arrangement of the extracellular matrix's collagenous components in the maturing scar—shaping the mechanical properties that support its structural stability. While this suggests an adaptive role for CCN1 in regulating collagen structural attributes crucial for supporting scar integrity post MI, the long-term protracted expression of CCN1 holds maladaptive implications, potentially diminishing collagen structural complexity and compliance in non-infarct regions.

Bimetallic Nanoplatforms for Prostate Cancer Treatment by Interfering Cellular Communication.

Cellular communication mediated by messenger molecules plays an important role in the progression of cancer. Herein, pH-sensitive zeolitic imidazolate framework-8 (ZIF-8) loaded with PtCl2(OH)2(NH3)2 [i.e., Pt(IV)] bimetallic nanoplatforms were developed for prostate cancer therapy by interfering inositol-1, 4, 5-trisphosphate (IP3)-mediated cellular communication. As an important messenger in cells, the function of IP3 was found to be efficiently interfered with by the Pt(IV)-binding inositol unit. This finding effect of Pt(IV) is totally different from its traditional function as a prodrug of cis-platinum for chemotherapy. The decreased IP3 signal further downregulated the cytoplasmic Ca2+ concentration and downstream signal transduction to inhibit proliferation and invasion of tumor cells. Meanwhile, Zn2+ released from ZIF-8 under an acidic tumor microenvironment decreased adenosine triphosphate biosynthesis, which could further limit the cellular communication. Such a proposed strategy of interfering cellular communication has demonstrated its feasibility in this study, which may provide new perspectives for cancer therapy.

DISSyphilis and the risk of HIV infection: A Mendelian randomization study.

To assess the causal effect of syphilis on HIV infection by Mendelian randomization analysis. The data of syphilis and HIV infection were obtained from genome-wide association studies, Mendelian randomization analyses were conducted using methods such as weighted median, MR Egger, and inverse variance to evaluate the causal relationship between syphilis and HIV infection. Gene expression data of persons living with HIV (PLWH) and single-cell RNA sequencing profiles were obtained from the GEO database. Analysis involved the identification of key molecules and relevant signaling pathways. MR analysis showed a significant causal relationship between syphilis and HIV infection (WM, OR: 1.098, 95%CI: 1.033-1.217, P = 0.003; IVW, OR: 1.095, 95%CI: 1.048-1.145, P < 0.001). We discovered that rs138697742, a genetic variant related to the RPAIN gene, is associated with HIV infection, and influences the expression of RPAIN, possibly contributing to the progression of the disease. Moreover, single-cell data analysis revealed the cellular communication patterns within PLWH, with monocytes appearing to play a crucial role. In summary, our study reveals a direct causal relationship between syphilis and HIV infection. Additionally, the upregulation of RPAIN gene expression resulting from genetic mutations may serve as a key factor in promoting the progression of HIV infection. Targeting the RPAIN/GALECTIN merges as a promising novel therapeutic target for managing HIV infection.