MolProphet: A One-Stop, General Purpose, and AI-Based Platform for the Early Stages of Drug Discovery.

Artificial intelligence (AI) is an effective tool to accelerate drug discovery and cut costs in discovery processes. Many successful AI applications are reported in the early stages of small molecule drug discovery. However, most of those applications require a deep understanding of software and hardware, and focus on a single field that implies data normalization and transfer between those applications is still a challenge for normal users. It usually limits the application of AI in drug discovery. Here, based on a series of robust models, we formed a one-stop, general purpose, and AI-based drug discovery platform, MolProphet, to provide complete functionalities in the early stages of small molecule drug discovery, including AI-based target pocket prediction, hit discovery and lead optimization, and compound targeting, as well as abundant analyzing tools to check the results. MolProphet is an accessible and user-friendly web-based platform that is fully designed according to the practices in the drug discovery industry. The molecule screened, generated, or optimized by the MolProphet is purchasable and synthesizable at low cost but with good drug-likeness. More than 400 users from industry and academia have used MolProphet in their work. We hope this platform can provide a powerful solution to assist each normal researcher in drug design and related research areas. It is available for everyone at https://www.molprophet.com/.

Boosted Electrocatalytic Degradation of Levofloxacin by Chloride Ions: Performances Evaluation and Mechanism Insight with Different Anodes.

As chloride (Cl-) is a commonly found anion in natural water, it has a significant impact on electrocatalytic oxidation processes; yet, the mechanism of radical transformation on different types of anodes remains unexplored. Therefore, this study aims to investigate the influence of chlorine-containing environments on the electrocatalytic degradation performance of levofloxacin using BDD, Ti4O7, and Ru-Ti electrodes. The comparative analysis of the electrode performance demonstrated that the presence of Cl- improved the removal and mineralization efficiency of levofloxacin on all the electrodes. The enhancement was the most pronounced on the Ti4O7 electrode and the least significant on the Ru-Ti electrode. The evaluation experiments and EPR characterization revealed that the increased generation of hydroxyl radicals and active chlorine played a major role in the degradation process, particularly on the Ti4O7 anode. The electrochemical performance tests indicated that the concentration of Cl- affected the oxygen evolution potentials of the electrode and consequently influenced the formation of hydroxyl radicals. This study elucidates the mechanism of Cl- participation in the electrocatalytic degradation of chlorine-containing organic wastewater. Therefore, the highly chlorine-resistant electrocatalytic anode materials hold great potential for the promotion of the practical application of the electrocatalytic treatment of antibiotic wastewater.

Effect of terahertz electromagnetic field on single-file water transport through a carbon nanotube.

With the advancement in terahertz technology, the terahertz electromagnetic field has been proven to be an effective strategy to tune the nanofluidic transport. In this study, we utilize molecular dynamics simulations to systematically analyze the transport of single-file water through a carbon nanotube (CNT) under terahertz electromagnetic fields, focusing on the CNT length, field strength, polarization direction and frequency. Strikingly, with the increase in field strength, the water flow exhibits a transition from normal to super permeation states because of the resonance effect, and the threshold field shifts to low values for long CNTs. The field component parallel to the CNT axis contributes to the resonance effect and increasing water flow, but the vertical component maintains the structure of the single-file water chain and even impedes the water flow. As a result, for a continuous change of field direction, the water flow changes from super permeation to normal states. With the increase in field frequency, the water flow also changes from super permeation to normal or even frozen states, where a higher frequency is required to trigger the super permeation states for lower field strength. Our results provide a comprehensive insight into the effect of terahertz electromagnetic field on the transport of single-file water chains and should have great implications for designing novel nanofluidic devices.

CAFs-secreted exosomal cricN4BP2L2 promoted colorectal cancer stemness and chemoresistance by interacting with EIF4A3.

Cancer-associated fibroblasts secreted exosomes (CAFs-exo) are important for tumor carcinogenesis and chemoresistance, but its underlying mechanism in colorectal cancer (CRC) has not yet been clarified. In this study, we investigated the regulatory mechanism of CAFs-exo cricN4BP2L2 on the proliferation, apoptosis, stemness and chemoresistance of LoVo cells. We found that CAFs-exo promoted the oxaliplatin resistance and stemness of LoVo cells, while inhibited the LoVo cell apoptosis. Moreover, knockdown of cricN4BP2L2 in CAFs-exo inhibited the oxaliplatin resistance and stemness characteristics of LoVo cells. Mechanistically, cricN4BP2L2 regulated PI3K/AKT/mTOR axis by binding to EIF4A3. Rescue experiments proved that CAFs-derived exosomal cricN4BP2L2 promoted CRC cells stemness and oxaliplatin resistance by upregulating EIF4A3. Moreover, in vivo experiments showed that depletion of cricN4BP2L2 suppressed CRC tumorigenesis growth. In conclusion, CAFs-exo cricN4BP2L2 promoted the CRC cells stemness and oxaliplatin resistance through EIF4A3/PI3K/AKT/mTOR pathway.

The subacute toxicity and underlying mechanisms of biomimetic mesoporous polydopamine nanoparticles.

Recently, mesoporous nanomaterials with widespread applications have attracted great interest in the field of drug delivery due to their unique structure and good physiochemical properties. As a biomimetic nanomaterial, mesoporous polydopamine (MPDA) possesses both a superior nature and good compatibility, endowing it with good clinical transformation prospects compared with other inorganic mesoporous nanocarriers. However, the subacute toxicity and underlying mechanisms of biomimetic mesoporous polydopamine nanoparticles remain uncertain. Herein, we prepared MPDAs by a soft template method and evaluated their primary physiochemical properties and metabolite toxicity, as well as potential mechanisms. The results demonstrated that MPDA injection at low (3.61 mg/kg) and medium doses (10.87 mg/kg) did not significantly change the body weight, organ index or routine blood parameters. In contrast, high-dose MPDA injection (78.57 mg/kg) is associated with disturbances in the gut microbiota, activation of inflammatory pathways through the abnormal metabolism of bile acids and unsaturated fatty acids, and potential oxidative stress injury. In sum, the MPDA dose applied should be controlled during the treatment. This study first provides a systematic evaluation of metabolite toxicity and related mechanisms for MPDA-based nanoparticles, filling the gap between their research and clinical transformation as a drug delivery nanoplatform.

CircN4BP2L2 promotes colorectal cancer growth and metastasis through regulation of the miR-340-5p/CXCR4 axis.

Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide. Dysregulation of circular RNAs (circRNAs) appears to be a critical factor in CRC progression. However, mechanistic studies delineating the role of circRNAs in CRC remain limited. In this study, qRT-PCR and western blot assays were used to measure the expression of genes and proteins. Migration, invasion, proliferation, and apoptosis were examined by wound-healing, transwell, CCK-8, colony formation, and flow cytometry assays, respectively. Molecular interactions were validated by a dual-luciferase report system. A xenograft animal model was established to examine in vivo tumor growth and lung metastasis. Our data indicated that circN4BP2L2 expression was increased in CRC tissues and cell lines. Notably, inhibition of circN4BP2L2 effectively inhibited proliferation, migration, and invasion of LoVo cells, and inhibited tumor growth and metastasis in vivo, whereas the forced expression of circN4BP2L2 facilitated the proliferation, migration, and invasion of HT-29 cells. Mechanistic studies revealed that circN4BP2L2 acted as a molecular sponge of miR-340-5p to competitively promote CXCR4 expression. Furthermore, inhibition of miR-340-5p reversed the anti-cancer effects of circN4BP2L2 or CXCR4 silencing. Our data indicated an oncogenic role of circN4BP2L2 in CRC via regulation of the miR-340-5p/CXCR4 axis, which may be a promising biomarker and target for CRC treatment.

LncRNA HCG18 upregulates TRAF4/TRAF5 to facilitate proliferation, migration and EMT of epithelial ovarian cancer by targeting miR-29a/b.

BACKGROUND: Although long noncoding RNA HLA complex group 18 (lncRNA HCG18) has been suggested to regulate cell growth in several tumours, the function of HCG18 in epithelial ovarian cancer (EOC) and its mechanism are still unclear. METHODS: shRNAs were applied to reduce HCG18 and related genes. For overexpression of miRNA, a miRNA mimic was transfected into cells. Quantitative real-time PCR (qRT-PCR) was used to detect levels of HCG18, miR-29a/b, and mRNAs. MTT, colony formation, wound healing and Transwell assays were used to evaluate cell proliferation, migration and invasion, respectively. A luciferase reporter assay was utilized to evaluate NF-κB activity and the binding of miRNAs with HCG18 or TRAF4/5. BALB nude mice injected with cells stably expressing shHCG18 or shNC were used for in vivo modelling. Subcutaneous tumour growth was monitored in nude mice, and immunohistochemistry (IHC) was used to determine expression of the proliferation marker Ki67. RESULTS: Abnormal expression of HCG18 and miR-29a/b was observed in EOC tissues. Knockdown of HCG18 using shRNA inhibited proliferation, migration, EMT and the proinflammatory pathway in EOC cells. miR-29a/b mimics and TRAF4/5 knockdown exhibited effects similar to HCG18 knockdown. Further experiments suggested that HCG18 directly targets miR-29a/b and upregulates TRAF4/5 expression, which are inhibited by targeting miR-29a/b. Moreover, overexpression of TRAF4/5 antagonized the inhibitory effect of HCG18 knockdown, suggesting that they are involved in HCG18-mediated oncogenic effects. Silencing HCG18 reduced tumour size and levels of Ki67 and TRAF4/5 while increasing miR-29a/b levels in vivo. CONCLUSIONS: Taken together, our data revealed an oncogenic signalling pathway mediated by HCG18 in ovarian cell lines, which functions as a ceRNA of miR-29a/b and thus derepresses expression levels of TRAF4/5, facilitating NF-κB pathway-mediated promotion of EOC cell proliferation and migration.

CAF-derived midkine promotes EMT and cisplatin resistance by upregulating lncRNA ST7-AS1 in gastric cancer.

This study aimed to investigate the role of cancer-associated fibroblast (CAF)-derived midkine (MK) in cisplatin (DDP) resistance. The primary cultures of CAFs and non-cancer fibroblasts (NFs) were isolated and purified. The DDP-resistant gastric cancer (GC) cells were cultured with CAF-conditioned medium. QRT-PCR and Elisa assays were employed to determine MK expression. The expression of ST7-AS1 was measured by qRT-PCR. The impact of CAFs, MK, and ST7-AS1 silencing on DDP resistance was determined by MTT and Annexin V/PI staining assay. Expression of EMT markers and PI3K/AKT was determined by Western blot and qRT-PCR. The role of MK in DDP resistance was confirmed in a xenograft model. Incubation with CAF-conditioned medium increased the IC50 to DDP. Also, incubation with CAF-conditioned medium increased cell viability, reduced cell apoptosis, and promoted EMT in DDP-resistant GC cells, which were all blocked with MK neutralization antibody treatment. MK increased the DDP resistance and upregulated the expression of ST7-AS1 in DDP-resistant GC cells. Additionally, ST7-AS1 knockdown increased the sensitivity to DDP by inhibiting EMT. Moreover, ST7-AS1 knockdown significantly decreased the phosphorylation of PI3K and AKT, and suppressed EMT, which were restored by MK addition. Finally, MK promoted tumor growth and DDP resistance in a mice model bearing the SGC-7901/DDP xenografts. CAF-derived MK promotes EMT-mediated DDP resistance via upregulation of ST7-AS1 and activation of PI3K/AKT pathway.

A 10-year bibliometric analysis of osteosarcoma and cure from 2010 to 2019.

BACKGROUND: In recent decades, the 5-year survival rate of osteosarcoma remains poor, despite the variety of operations, and exploration of drug therapy has become the key to improvement. This study investigates the contribution of different aspects in osteosarcoma and cure, and predicts research hotspots to benefit future clinical outcomes. METHODS: The Web of Science and PubMed databases were queried to collect all relevant publications related to osteosarcoma and cure from 2009 to 2019. These data were imported into CiteSpace and the Online Analysis Platform of Literature Metrology for bibliometric analysis. Bi-clustering was performed on Bibliographic Item co-occurrence Matrix Builder (BICOMB) and gCLUTO to identify hotspots. Additionally, completed clinical trials on osteosarcoma with results past phase II were collated. RESULTS: A total of 2258 publications were identified in osteosarcoma and cure from 2009 to 2019. China has the largest number of publications (38.49%), followed by the United States (23.03%) with the greatest impact (centrality = 0.44). The centrality of most institutions is < 0.1, and Central South University and Texas MD Anderson Cancer Center possess the highest average citation rates of 3.25 and 2.87. BMC cancer has the highest average citation rate of 3.26 in 772 journals. Four authors (Picci P, Gorlick R, Bielack SS and Bacci G) made the best contributions. We also identified eight hotspots and collected 41 clinical trials related to drug research on osteosarcoma. CONCLUSIONS: The urgent need exists to strengthen global academic exchanges. Overcoming multidrug resistance in osteosarcoma is the focus of past, present and future investigations. Transformation of the metastasis pattern, microenvironment genetics mechanism, alternative methods of systemic chemotherapy and exploration of traditional Chinese medicine is expected to contribute to a new upsurge of research.

Temperature dependence of the transport of single-file water molecules through a hydrophobic channel.

Although great effort has been made on the transport properties of water molecules through nanometer channels, our understanding on the effect of some basic parameters are still rather poor. In this article, we use molecular dynamics simulations to study the temperature effect on the transport of single-file water molecules through a hydrophobic channel. Of particular interest is that the water flow and average translocation time both exhibit exponential relations with the temperature. Based on the continuous-time random-walk model and Arrhenius equation, we explore some new physical insights on these exponential behaviors. With the increase of temperature, the water dipoles flip more frequently, since the estimated flipping barrier is less than 2 kB T. Specifically, the flipping frequency also shows an exponential relation with the temperature. Furthermore, the water-water interaction and water occupancy demonstrate linear relations with the temperature, and the water density profiles along the channel axis can be slightly affected by the temperature. These results not only enhance our knowledge about the temperature effect on the single-file water transport, but also have potential implications for the design of controllable nanofluidic machines.

A current-driven nanometer water pump.

The design of a water pump, which has huge potential for applications in nanotechnology and daily life, is the dream of many scientists. In this paper, we successfully design a nanometer water pump by using molecular dynamics simulations. Ions of either sodium or chlorine in a narrow channel will generate electric current under electric fields, which then drives the water through a wider channel, similar to recent experimental setups. Considerable water flux is achieved within small field strengths that are accessible by experimentation. Of particular interest, is that for sodium the water flux increases almost linearly with field strengths; while for chlorine there exists a critical field strength, the water flux exhibits a plateau before the critical value and increases linearly after it. This result follows the behavior of ion velocity, which is related to friction behavior. We also estimate the power and energy consumption for such a pump, and compare it to the macroscopic mechanical pumps. A further comparison suggests that different ions will have different pumping abilities. This study not only provides new, significant results with possible connection to existing research, but has tremendous potential application in the design of nanofluidic devices.

Ultra-fast single-file transport of a simple liquid beyond the collective behavior zone.

We use molecular dynamics simulations to analyze the single-file transport behavior of a simple liquid through a narrow membrane channel. With the decrease of the liquid-channel interaction, the liquid flow exhibits a remarkable maximum behavior owing to the competition of liquid-liquid and liquid-channel interactions. Surprisingly, this maximum flow is coupled to a sudden reduce of the liquid occupancy, where the liquid particle is moving through the channel alone at nearly constant velocity, rather than in a collective motion mode. Further investigation on the encountered energy barrier suggests that this maximum flow should be induced by particles having large instant velocities (or thermal fluctuation) that overcome the liquid-liquid and liquid-channel interaction barriers. Further decreasing the liquid-channel interaction leads to the decrease and ultimate stabilization of the liquid flow, since the energy barrier will increase and becomes steady. These results suggest that the breakdown of collective behavior can be a new rule for achieving fast single-file transportation, especially for simple or nonpolar liquids with relatively weak liquid-liquid interactions, and is thus helpful for the design of high flux nanofluidic devices.

On the Origin of Water Flow through Carbon Nanotubes.

The transport of water molecules through carbon nanotubes (CNTs) is of primary importance for understanding water-mediated biological activities as well as for the design of novel nanoporous materials. Herein, we analyze the water flow through CNTs by using molecular dynamics simulations with the hope of finding basic parameters determining the flow value. Of particular interest is that a simple equation as a function of water diffusion, occupancy and CNT size, can well describe the water flow through CNTs with different sizes. Specifically, both the simulation and equation flow exhibit power law relations with the CNT diameter and length, where the two exponents are close to each other. The water occupancy and translocation time also demonstrate interesting relations with the CNT size. The water dipole orientations and density profiles are also sensitive to the change of CNT size. These results greatly enhance our knowledge on the nature of water flow through CNTs and are helpful in predicting the water flow of CNTs up to the experimental length scale.

MicroRNA 520d-3p inhibits gastric cancer cell proliferation, migration, and invasion by downregulating EphA2 expression.

Aberrant expression of microRNAs (miRNAs) has been shown to play important roles in cancer progression as a result of changes in expression of their target genes. In this study, we investigated the roles of miR-520d-3p on gastric cancer (GC) cell proliferation, migration, and invasion, and confirmed that this miRNA regulates EphA2 expression. The mRNA expression levels of miR-520d-3p and EphA2 in GC tissues and cell lines were evaluated. The clinical and prognostic significance of miR-520d-3p was assessed. The biological function of miR-520d-3p in GC cells was investigated using a methylthiazolyldiphenyl-tetrazolium bromide assay, cell cycle assay, transwell invasion assay, and wound-healing assay. miR-520d-3p expression was down-regulated and inversely correlated with the expression of EphA2 in GC tissues and cell lines. Lower expression of miR-520d-3p was associated with tumor invasion (P = 0.0357), lymph nodes metastasis (P = 0.0272), a higher clinical stage (P = 0.0041), and poorer overall survival (P = 0.0105). Luciferase assays revealed that miR-520d-3p inhibited EphA2 expression by targeting the 3'-untranslated region of EphA2 mRNA. Overexpression of miR-520d-3p dramatically inhibited the proliferation, cell cycle progression, invasion, and migration of GC cells, while down-regulation substantially promoted these properties. Moreover, c-Myc, CyclinD1, and matrix metalloproteinase-9 expression levels were down-regulated in miR-520d-3p mimic-transfected cells and up-regulated in miR-520d-3p inhibitor-transfected cells. Taken together, our data showed that miR-520d-3p appears to contribute to GC progression via the regulation of EphA2 and could serve as a novel prognostic and potential therapeutic marker.

Translocation of a nanoparticle through a fluidic channel: the role of grafted polymers.

The surface properties of nanoparticles (NPs) are key factors for their design and use in biomedicine; however, our understanding of the effect of surface properties on the translocation of NPs through membranes is still rather poor. Herein, we have used molecular dynamics simulations to study the translocation of a polymer-grafted NP through a fluidic channel. We change the length, number, amount of charge and the charge position of grafted polymers. With the increase of polymer length, the NP flux decreases as a whole due to the increase of NP size, where the -NP translocation fails at the smallest polymer length, because of the strong binding of Na(+). Surprisingly, the NP flux exhibits a maximum with the increase of the polymer number or charge amount, which is co-determined by the NP net charge and size. Owing to the NP-membrane adsorption and NP-ion binding, the NP flux decreases with the decrease of charge position. We also analyze the transport of counterions, which depends on both the NP-ion binding and NP dynamics. Finally, we investigate the effect of electric fields for a given NP type. Our results reveal the important role of grafted polymers in the NP translocation and may have implications in the design of highly efficient NP delivery.

DNA methylation regulator-based molecular subtyping and tumor microenvironment characterization in hepatocellular carcinoma.

Backgroud: Although recent studies have reported the regulation of the immune response in hepatocellular carcinoma (HCC) through DNA methylation, the comprehensive impact methylation modifications on tumor microenvironment characteristics and immunotherapy efficacy has not been fully elucidated. Methods: In this research, we conducted a comprehensive assessment of the patterns of DNA methylation regulators and the profiles of the tumor microenvironment (TME) in HCC, focusing on 21 specific DNA methylation regulators. We subsequently developed a unique scoring system, a DNA methylation score (DMscore), to assess the individual DNA methylation modifications among the three distinct methylation patterns for differentially expressed genes (DEGs). Results: Three distinct methylation modification patterns were identified with distinct TME infiltration characteristics. We demonstrated that the DMscore could predict patient subtype, TME infiltration, and patient prognosis. A low DMscore, characterized by an elevated tumor mutation burden (TMB), hepatitis B virus (HBV)/hepatitis C virus (HCV) infection, and immune activation, indicates an inflamed tumor microenvironment phenotype with a 5-year survival rate of 7.8%. Moreover, a low DMscore appeared to increase the efficacy of immunotherapy in the anti-CTLA-4/PD-1/PD-L1 cohort. Conclusions: In brief, this research has enhanced our understanding of the correlation between modifications in DNA methylation patterns and the profile of the tumor microenvironment in individuals diagnosed with HCC. The DMscore may serve as an alternative biomarker for survival and efficacy of immunotherapy in patients with HCC.

Meta Learning with Attention Based FP-GNNs for Few-Shot Molecular Property Prediction.

Molecular property prediction holds significant importance in drug discovery, enabling the identification of biologically active compounds with favorable drug-like properties. However, the low data problem, arising from the scarcity of labeled data in drug discovery, poses a substantial obstacle for accurate predictions. To address this challenge, we introduce a novel architecture, AttFPGNN-MAML, for few-shot molecular property prediction. The proposed approach incorporates a hybrid feature representation to enrich molecular representations and model intermolecular relationships specific to the task. By leveraging ProtoMAML, a meta-learning strategy, our model is trained and adapted to new tasks. Evaluation on two few-shot data sets, MoleculeNet and FS-Mol, demonstrates our method's superior performance in three out of four tasks and across various support set sizes. These results convincingly validate the effectiveness of our method in the realm of few-shot molecular property prediction. The source code is publicly available at https://github.com/sanomics-lab/AttFPGNN-MAML.

Obesity and lipid metabolism in the development of osteoporosis (Review).

Osteoporosis is a common bone metabolic disease that causes a heavy social burden and seriously threatens life. Improving osteogenic capacity is necessary to correct bone mass loss in the treatment of osteoporosis. Osteoblasts are derived from the differentiation of bone marrow mesenchymal stem cells, a process that opposes adipogenic differentiation. The peroxisome proliferator­activated receptor γ and Wnt/ß­catenin signaling pathways mediate the mutual regulation of osteogenesis and adipogenesis. Lipid substances play an important role in the occurrence and development of osteoporosis. The content and proportion of lipids modulate the activity of immunocytes, mainly macrophages, and the secretion of inflammatory factors, such as IL­1, IL­6 and TNF­α. These inflammatory effectors increase the activity and promote the differentiation of osteoclasts, which leads to bone imbalance and stronger bone resorption. Obesity also decreases the activity of antioxidases and leads to oxidative stress, thereby inhibiting osteogenesis. The present review starts by examining the bidirectional differentiation of BM­MSCs, describes in detail the mechanism by which lipids affect bone metabolism, and discusses the regulatory role of inflammation and oxidative stress in this process. The review concludes that a reasonable adjustment of the content and proportion of lipids, and the alleviation of inflammatory storms and oxidative damage induced by lipid imbalances, will improve bone mass and treat osteoporosis.

Single-cell RNA sequencing reveals that an imbalance in monocyte subsets rather than changes in gene expression patterns is a feature of postmenopausal osteoporosis.

The role of monocytes in postmenopausal osteoporosis is widely recognized; however, the mechanisms underlying monocyte reprogramming remain unknown. In this study, single-cell RNA sequencing (scRNA-seq) was conducted on CD14+ bone marrow monocytes obtained from three postmenopausal women with normal bone mineral density (BMD) and three women with postmenopausal osteoporosis (PMOP). Monocle2 was used to classify the monocytes into 7 distinct clusters. The proportion of Cluster 1 significantly decreased in PMOP patients, while the proportion of Cluster 7 increased. Further analysis via GSEA, transcription factor activity analysis, and sc-metabolic analysis revealed significant differences between Clusters 1 and 7. Cluster 7 exhibited upregulated pathways associated with inflammation, immunity, and osteoclast differentiation, whereas Cluster 1 demonstrated the opposite results. Monocle2, TSCAN, VECTOR and scVelo data indicated that Cluster 1 represented the initial subset and that Cluster 7 represents one of the terminal subsets. BayesPrism and ssGSEA were employed to analyze the bulk transcriptome data obtained from the GEO database. The observed alterations in the proportions of Clusters 1 and 7 were validated and found to have diagnostic significance. CD16 serves as the marker gene for Cluster 7, thus leading to an increased proportion of CD16+ monocytes in women with PMOP. Flow cytometry was used to assess the consistency of outcomes with those of the bioinformatic analysis. Subsequently, an additional scRNA-seq analysis was conducted on bone marrow mononuclear cells obtained from three patients with PMOP and three postmenopausal women with normal BMD. The differential proportions of Cluster 1 and Cluster 7 were once again confirmed, with the pathological effect of Cluster 7 may attribute to cell-cell communication. The scRNA-seq findings suggest that an imbalance in monocyte subsets is a characteristic feature of PMOP. These findings elucidate the limitations of utilizing bulk transcriptome data for detecting alterations in monocytes, which may influence novel research inquiries.

Monocytes are a type of white blood cell that plays a role in postmenopausal osteoporosis (PMOP), a condition where bones become weak and brittle after menopause. However, how monocytes change in this condition is not fully understood. In this study, single-cell RNA sequencing was used to analyze bone marrow monocytes from postmenopausal women with normal bone density and those with osteoporosis. Two distinct types of monocytes were identified, which were called Clusters 1 and 7. In women with PMOP, there was a decrease in Cluster 1 monocytes and an increase in Cluster 7 monocytes. This change was validated in external data sets and in peripheral blood. Further analysis showed that Cluster 7 monocytes positively correlated with inflammation, immunity, and osteoclast differentiation (a process that leads to bone resorption). Cluster 1 monocytes were found to be the initial subset, while Cluster 7 monocytes were one of the terminal subsets. Overall, this study suggests that an imbalance in monocyte subsets is a characteristic feature of postmenopausal osteoporosis. These findings have important implications for understanding the role of monocytes in bone health.

Comprehensive analysis regarding the prognostic significance of downregulated ferroptosis-related gene AKR1C2 in gastric cancer and its underlying roles in immune response.

Ferroptosis is a cell death form that has been reported to be involved in the progression of gastric cancer (GC). However, the underlying mechanism of ferroptosis in GC still needs to be further explored. This study conducted a survey regarding the biological functions of ferroptosis-related gene AKR1C2 in GC. Multiple bioinformatic platforms were applied to indicate that the expression level of AKR1C2 was downregulated in GC tissues, which displayed good prognostic value. Clinical statistics proved that AKR1C2 expression was correlated with several tumor characteristics of GC patients, such as characteristics of N-stage tumor or residual tumor. Additionally, LinkedOmics was employed to explore the co-expression network and molecular pathways of AKR1C2 in GC. Eventually, AKR1C2 was found to be involved in several immune-related signatures, such as immunostimulators, immunoinhibitors, chemokines and chemokine receptors. To sum up, these results may provide a novel insight into the significance and biological functions of ferroptosis-related gene AKR1C2 in GC tumorigenesis.