Research progress in mitochondrial quality control in schizophrenia. / çº¿ç²’ä½“è´¨é‡æŽ§åˆ¶åœ¨ç²¾ç¥žåˆ†è£‚ç—‡ä¸­çš„ç ”ç©¶è¿›å±•.

Mitochondria are the main site of energy metabolism within cells, generating a substantial amount of ATP to supply energy to the human body. Research has shown that alterations in mitochondrial structure and function exist in individuals with schizophrenia, suggesting their potential impact on the onset of psychiatric disorders and clinical treatment efficacy. Therefore, understanding the research progress on the genetic mechanisms, pathological processes, image manifestations of schizophrenia and mitochondrial quality control, and summarizing the relevant evidence of mitochondrial-related targets as potential therapeutic targets for schizophrenia, can provide references for further research.

Unraveling the immunological landscape in acute pancreatitis progression to sepsis: insights from a Mendelian randomization study on immune cell traits.

Background: Acute pancreatitis (AP) is a severe digestive system disorder with a significant risk of progressing to sepsis, a major cause of mortality. Unraveling the immunological pathways in AP is essential for developing effective treatments, particularly understanding the role of specific immune cell traits in this progression. Methods: Employing a bidirectional two-sample Mendelian Randomization (MR) approach, this study first examined the causal relationship between AP and 731 immune cell traits to identify those significantly associated with AP. Subsequently, we explored the causal associations between 731 immune cell traits and sepsis. The analysis utilized extensive genome-wide association studies (GWAS) summary datasets, with a focus on identifying common immune cell traits with statistically significant causal associations between AP and sepsis. Results: Our investigation identified 44 immune cell traits unidirectionally associated with AP and 36 traits unidirectionally associated with sepsis. Among these, CD127 on CD28+ CD45RA- CD8+ T cells emerged as a common mediator, accounting for 5.296% of the increased risk of sepsis in AP patients. This finding highlights the significant role of specific memory CD8+ T cells in the pathophysiology of AP and its progression to sepsis. Conclusion: This study elucidates the critical role of specific immune cell traits, particularly CD127hi memory CD8+ T cells, in the progression of AP to sepsis. Our findings provide a foundation for future research into targeted immune-modulatory therapies, potentially improving patient outcomes in AP-related sepsis and offering new insights into the complex immunological dynamics of this condition.

Identification of TAP1 as a T-cell related therapeutic target in gastric cancer by mediating oxalipliatin-related synergistic enhancement of immunotherapy.

BACKGROUND: Given the intricate molecular complexities and heterogeneity inherent in T-cell immunotherapy of gastric cancer (GC), elucidative T-cell-related biomarkers were imperative needed for facilitating the prediction of GC patient prognosis and identify potential synergistic therapeutic targets. METHODS: We conducted COX regression analysis in TISIDB, TCGA-STAD, and GEO databases to identify 19 GC T-cell-mediated sensitivity tumor killing (TTK) genes (key GCTTKs). Based on key GCTTKs, we constructed two TTK patterns and analyzed their metabolic pathways, mutation features, clinical data distribution, immune cell infiltration, and prognosis. LASSO regression was performed to develop a T-cell-mediated GC Prognosis (TGCP) model. We validated the TGCP model in GC patients. TAP1 was further selected for investigation of its biological functions and molecular mechanisms. We assessed the potential of TAP1 as a promising therapeutic target for GC using Patient-derived organoids (PDOs)-derived xenografts (PDOXs) models of GC. RESULTS: The TTK patterns display notable disparities. The TGCP model showcases its proficiency in predicting immune response efficacy, effectively distinguishes immunotherapy difference GC patients. Our findings find further confirmation in PDOX models, affirming TAP1 can enhance immunotherapy facilitated by PDL1 inhibitors. Furthermore, Oxaliplatin, by promoting TAP1 expression, augments PDL1 expression, thereby enhancing the efficacy of immunotherapy. CONCLUSIONS: We constructed a TGCP model, which demonstrates satisfactory predictive accuracy. Out of 9 prognostic genes, TAP1 was validated as a synergistic target for Oxaliplatin and PDL1 inhibitors, offering a genetic-level explanation for the synergy observed in GC treatment involving Oxaliplatin in combination with PDL1 inhibitors.

Kinesin Family Member-18A (KIF18A) Promotes Cell Proliferation and Metastasis in Hepatocellular Carcinoma.

BACKGROUND & AIMS: Kinesin family member 18A (KIF18A) is notable for its aberrant expression across various cancer types and its pivotal role is driving cancer progression. In this study, we aim to investigate the intricate molecular mechanisms underlying the impact of KIF18A on the progression of HCC. METHODS: Western blotting assays, a quantitative real-time PCR and immunohistochemical analyses were performed to quantitatively assess KIF18A expression in HCC tissues. We then performed genetic manipulations within HCC cells by silencing endogenous KIF18A using short hairpin RNA (shRNA) and introducing exogenous plasmids to overexpress KIF18A. We monitored cell progression, analyzed cell cycle and cell apoptosis and assessed cell migration and invasion both in vitro and in vivo. Moreover, we conducted RNA-sequencing to explore KIF18A-related signaling pathways utilizing Reactome and KEGG enrichment methods and validated these critical mediators in these pathways. RESULTS: Analysis of the TCGA-LIHC database revealed pronounced overexpression of KIF18A in HCC tissues, the finding was subsequently confirmed through the analysis of clinical samples obtained from HCC patients. Notably, silencing KIF18A in cells led to an obvious inhibition of cell proliferation, migration and invasion in vitro. Furthermore, in subcutaneous and orthotopic xenograft models, suppression of KIF18A sgnificantly redudce tumor weight and the number of lung metastatic nodules. Mechanistically, KIF18A appears to facilitate cell proliferation by upregulating MAD2 and CDK1/CyclinB1 expression levels, with the activation of SMAD2/3 signaling contributing to KIF18A-driven metastasis. CONCLUSION: Our study elucidates the molecular mechanism by which KIF18A mediates proliferation and metastasis in HCC cells, offering new insights into potential therapeutic targets.

Pyroptosis is involved in the immune microenvironment regulation of unexplained recurrent miscarriage.

Unexplained recurrent miscarriage (URM) is a common pregnancy complication with few effective therapies. Moreover, little is known regarding the role of pyroptosis in the regulation of the URM immune microenvironment. To address this issue, gene expression profiles of publicly available placental datasets GSE22490 and GSE76862 were downloaded from the Gene Expression Omnibus database. Pyroptosis-related differentially expressed genes were identified and a total of 16 differentially expressed genes associated with pyroptosis were detected, among which 1 was upregulated and 15 were downregulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that the functionally enriched modules and pathways of these genes are closely related to immune and inflammatory responses. Four hub genes were identified: BTK, TLR8, NLRC4, and TNFSF13B. BTK, TLR8, and TNFSF13B were highly connected with immune cells, according to the correlation analysis of four hub genes and 20 different types of immune cells (p < 0.05). The four hub genes were used as research objects to construct the interaction networks. Chorionic villus tissue was used for quantitative real-time polymerase chain reaction and western blot to confirm the expression levels of hub genes, and the results showed that the expression of the four hub genes was significantly decreased in the chorionic villus tissue in the URM group. Collectively, the present study indicates that perhaps pyroptosis is essential to the diversity and complexity of the URM immune microenvironment, and provides a theoretical basis and research ideas for subsequent target gene verification and mechanism research.

H3K18 lactylation-mediated VCAM1 expression promotes gastric cancer progression and metastasis via AKT-mTOR-CXCL1 axis.

The role of the Immunoglobulin Superfamily (IgSF) as adhesion molecules in orchestrating inflammation is pivotal, yet its specific involvement in gastric cancer (GC) remains unknown. We analyzed IgSF components and discerned conspicuously elevated VCAM1 expression in GC, correlating with a poor prognosis. Remarkably, VCAM1 enhances GC cell proliferation and migration by activating AKT-mTOR signaling. Moreover, lactate in the tumor microenvironment (TME) promotes dynamic lactylation of H3K18 (H3K18la), leading to transcriptional activation of VCAM1 in GC cells. Furthermore, VCAM1 actively mediates intercellular communication in the TME. AKT-mTOR-mediated CXCL1 expression is increased by VCAM1, facilitating the recruitment of human GC-derived mesenchymal stem cells (hGC-MSCs), thereby fostering immunesuppression and accelerating cancer progression. In summary, H3K18 lactylation upregulated VCAM1 transcription, which activated AKT-mTOR signaling, and promoted tumor cell proliferation, EMT Transition and tumor metastasis. VCAM1 upregulated CXCL1 expression by AKT-mTOR pathway, so as to facilitate hGC-MSCs and M2 macrophage recruitment and infiltration. These findings provide novel therapeutic targets for GC.

ZNF148 inhibits HBV replication by downregulating RXRα transcription.

BACKGROUND: Progressive hepatitis B virus (HBV) infection can result in cirrhosis, hepatocellular cancer, and chronic hepatitis. While antiviral drugs that are now on the market are efficient in controlling HBV infection, finding a functional cure is still quite difficult. Identifying host factors involved in regulating the HBV life cycle will contribute to the development of new antiviral strategies. Zinc finger proteins have a significant function in HBV replication, according to earlier studies. Zinc finger protein 148 (ZNF148), a zinc finger transcription factor, regulates the expression of various genes by specifically binding to GC-rich sequences within promoter regions. The function of ZNF148 in HBV replication was investigated in this study. METHODS: HepG2-Na+/taurocholate cotransporting polypeptide (HepG2-NTCP) cells and Huh7 cells were used to evaluate the function of ZNF148 in vitro. Northern blotting and real-time PCR were used to quantify the amount of viral RNA. Southern blotting and real-time PCR were used to quantify the amount of viral DNA. Viral protein levels were elevated, according to the Western blot results. Dual-luciferase reporter assays were used to examine the transcriptional activity of viral promoters. ZNF148's impact on HBV in vivo was investigated using an established rcccDNA mouse model. RESULTS: ZNF148 overexpression significantly decreased the levels of HBV RNAs and HBV core DNA in HBV-infected HepG2-NTCP cells and Huh7 cells expressing prcccDNA. Silencing ZNF148 exhibited the opposite effects in both cell lines. Furthermore, ZNF148 inhibited the activity of HBV ENII/Cp and the transcriptional activity of cccDNA. Mechanistic studies revealed that ZNF148 attenuated retinoid X receptor alpha (RXRα) expression by binding to the RXRα promoter sequence. RXRα binding site mutation or RXRα overexpression abolished the suppressive effect of ZNF148 on HBV replication. The inhibitory effect of ZNF148 was also observed in the rcccDNA mouse model. CONCLUSIONS: ZNF148 inhibited HBV replication by downregulating RXRα transcription. Our findings reveal that ZNF148 may be a new target for anti-HBV strategies.

MSCs-derived extracellular vesicles alleviate sepsis-associated liver dysfunction by inhibiting macrophage glycolysis-mediated inflammatory response.

Sepsis-associated liver dysfunction (SALD) aggravates the disease progression and prognosis of patients. Macrophages in the liver play a crucial role in the occurrence and development of SALD. Human umbilical cord mesenchymal stem cells (MSCs), by secreting extracellular vesicles (EVs), show beneficial effects in various inflammatory diseases. However, whether MSC-derived EVs (MSC-EVs) could ameliorate the inflammatory response in liver macrophages and the underlying mechanisms remain unclear. In this study, a mouse model of sepsis induced by lipopolysaccharide (LPS) challenge was used to investigate the immunomodulatory functions of MSC-EVs in SALD. LPS-stimulated primary Kupffer cells (KCs) and Raw264.7 were used to further explore the potential mechanisms of MSC-EVs in regulating the inflammatory response of macrophages. The results showed that MSC-EVs alleviated liver tissue injury and facilitated the polarization of M1 to M2 macrophages. Further in vitro studies confirmed that MSC-EVs treatment significantly downregulated the expression of several enzymes related to glycolysis and reduced the glycolytic flux by inhibiting hypoxia-inducible factor 1α (HIF-1α) expression, thus effectively inhibiting the inflammatory responses of macrophages. These findings reveal that the application of MSC-EVs might be a potential therapeutic strategy for treating SALD.

Efficient construction of a ß-naphthol library under continuous flow conditions.

A ß-naphthol library has been efficiently constructed utilizing a mild continuous flow procedure, relying on a tandem Friedel-Crafts reaction and starting from readily available arylacetyl chloride and alkynes. Multiple functionalized ß-naphthols can be acquired within 160 s in generally high yields (up to 83%). Using an electron-rich phenylacetyl chloride derivative (4-OH- or 4-MeO-) provides spirofused triene dione as the primary product. A scale-up preparation affords a throughput of 4.70 g h-1, indicating potential large-scale application. Herein, we present a rapid, reliable, and scalable method to obtain various ß-naphthols in the compound library.

Magnetic Fe3O4@SiO2 study on adsorption of methyl orange on nanoparticles.

Magnetic core-shell Fe3O4@SiO2 nanoparticles were synthesized by sol-gel method. Based on the characterization and experimental results, the adsorbent was found to have an average particle size of approximately 120 nm, a pore size range of 2-5 nm and superparamagnetic properties. It exhibited electrostatic and hydrogen bonding interactions during adsorption of methyl orange (MO). The adsorption of MO on the magnetic Fe3O4@SiO2 nanoparticles exhibited pseudo-second-order kinetics, the adsorption process is a spontaneous endothermic adsorption process, which conforms to the Langmuir adsorption isotherm model. he maximum amount of MO was adsorbed at pH = 2, T = 45 °C and t = 30 min, and the highest adsorption capacity was 182.503 mg/g; The unit adsorption capacity of the Fe3O4@SiO2 nanoparticles still reached 83% of the original capacity after 5 cycles, so the material was reusable and met the requirements of environmental protection. This study reveals the great potential of magnetic mesoporous nanoparticles for removal of dyes from wastewater.

Development of a fluorescent multiplexed lateral flow immunoassay for the simultaneous detection of crustacean allergen tropomyosin, sarcoplasmic calcium binding protein and egg allergen ovalbumin in different matrices and commercial foods.

A quantum dot (QD) based multiplexed lateral flow immunoassay (xLFIA) for the simultaneous detection of egg allergen ovalbumin, crustacean allergen tropomyosin (TM) and sarcoplasmic calcium binding protein (SCP) was developed in this study. QD-labeled rabbit anti-ovalbumin, SCP and TM antibodies were applied as fluorescent detection probes. The chromatography system was optimized to reduce the mutual interference of different test lines. Visual and instrumental detection limits of the xLFIA were 0.1 and 0.05 µg/mL for SCP, both 0.05 µg/mL for ovalbumin and both 0.5 µg/mL for TM. As low as 0.10 % crab powder, 0.01 % egg white powder and 0.05 % shrimp powder could be detected in all three model foods using xLFIA. Besides, the xLFIA detection results of 23 of 28 commercial foods were consistent with ingredient labels. These findings indicate that the developed xLFIA is a practical tool for point-of-care detection of egg and crustacean allergens in processed and commercial foods.

Genetic architecture of ear traits based on association mapping and co-expression networks in maize inbred lines and hybrids.

Ear traits are key contributors to grain yield in maize; therefore, exploring their genetic basis facilitates the improvement of grain yield. However, the underlying molecular mechanisms of ear traits remain obscure in both inbred lines and hybrids. Here, two association panels, respectively, comprising 203 inbred lines (IP) and 246 F1 hybrids (HP) were employed to identify candidate genes for six ear traits. The IP showed higher phenotypic variation and lower phenotypic mean than the HP for all traits, except ear tip-barrenness length. By conducting a genome-wide association study (GWAS) across multiple environments, 101 and 228 significant single-nucleotide polymorphisms (SNPs) associated with six ear traits were identified in the IP and HP, respectively. Of these significant SNPs identified in the HP, most showed complete-incomplete dominance and over-dominance effects for each ear trait. Combining a gene co-expression network with GWAS results, 186 and 440 candidate genes were predicted in the IP and HP, respectively, including known ear development genes ids1 and sid1. Of these, nine candidate genes were detected in both populations and expressed in maize ear and spikelet tissues. Furthermore, two key shared genes (GRMZM2G143330 and GRMZM2G171139) in both populations were found to be significantly associated with ear traits in the maize Goodman diversity panel with high-density variations. These findings advance our knowledge of the genetic architecture of ear traits between inbred lines and hybrids and provide a valuable resource for the genetic improvement of ear traits in maize. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01426-9.

Astaxanthin ameliorates dopaminergic neuron damage in paraquat-induced SH-SY5Y cells and mouse models of Parkinson's disease.

Parkinson's disease (PD) is the second largest neurodegenerative disorder caused by the decreased number of dopaminergic (DAc) neurons in the substantia nigra pars compacta (SNpc). There is evidence that oxidative stress can contribute degeneration of DAc neurons in SNpc which is mainly caused by apoptotic cell death. Thus, suppressing oxidative stress and apoptosis of DAc neurons is an effective strategy to mitigate the progress of PD. Astaxanthin (AST) is a carotenoid, which mainly exists in marine organisms and is a powerful biological antioxidant. In this study, we aimed to determine the neuroprotective effect of AST on paraquat (PQ) -induced models of PD in vitro and in vivo. Here, we showed that AST significantly enhanced cell survival of SH-SY5Y cells against PQ toxicity by suppressing apoptotic cell death and oxidative stress. Moreover, we found that AST significantly ameliorated PQ-induced behavioral disorders associated with PD in C57BL/6 J mice and the damage to DAc neurons in the SNpc of mice. Lastly, we found that the neuroprotective effects of AST were conducted through inhibiting PQ-induced activation of MAPK signaling. In conclusion, our study indicates that AST had a strong protective effect on PQ-induced oxidative stress and antagonized apoptotic cell death in SH-SY5Y cells and PQ-induced mice PD model, which might provide new insights of AST for PD treatment.

Menin orchestrates hepatic glucose and fatty acid uptake via deploying the cellular translocation of SIRT1 and PPARγ.

BACKGROUND: Menin is a scaffold protein encoded by the Men1 gene, which interacts with various transcriptional proteins to activate or repress cellular processes and is a key mediator in multiple organs. Both liver-specific and hepatocyte-specific Menin deficiency promotes high-fat diet-induced liver steatosis in mice, as well as insulin resistance and type 2 diabetic phenotype. The potential link between Menin and hepatic metabolism homeostasis may provide new insights into the mechanism of fatty liver disease. RESULTS: Disturbance of hepatic Menin expression impacts metabolic pathways associated with non-alcoholic fatty liver disease (NAFLD), including the FoxO signaling pathway, which is similar to that observed in both oleic acid-induced fatty hepatocytes model and biopsied fatty liver tissues, but with elevated hepatic Menin expression and inhibited FABP1. Higher levels of Menin facilitate glucose uptake while restraining fatty acid uptake. Menin targets the expression of FABP3/4/5 and also CD36 or GK, PCK by binding to their promoter regions, while recruiting and deploying the cellular localization of PPARγ and SIRT1 in the nucleus and cytoplasm. Accordingly, Menin binds to PPARγ and/or FoxO1 in hepatocytes, and orchestrates hepatic glucose and fatty acid uptake by recruiting SIRT1. CONCLUSION: Menin plays an orchestration role as a transcriptional activator and/or repressor to target downstream gene expression levels involved in hepatic energy uptake by interacting with the cellular energy sensor SIRT1, PPARγ, and/or FoxO1 and deploying their translocations between the cytoplasm and nucleus, thereby maintaining metabolic homeostasis. These findings provide more evidence suggesting Menin could be targeted for the treatment of hepatic steatosis, NAFLD or metabolic dysfunction-associated fatty liver disease (MAFLD), and even other hepatic diseases.

Chalcogen-doped, (seco)-hexabenzocoronene-based nanographenes: synthesis, properties, and chalcogen extrusion conversion.

A series of chalcogen-doped nanographenes (NGs) and their oxides are described. Their molecular design is conceptually based on the insertion of different chalcogens into the hexa-peri-hexabenzocoronene (HBC) backbone. All the NGs adopt nonplanar conformations, which would show better solubility compared to planar HBC. Except for the oxygen-doped, saddle-shaped NG, the insertion of large chalcogens like sulfur and selenium leads to a seco-HBC-based, helical geometry. All the three-dimensional structures are unambiguously confirmed by single-crystal X-ray diffractometry. Their photophysical properties including UV-vis absorption, fluorescence, chiroptical, charge distribution, and orbital gaps are investigated experimentally or theoretically. The properties of each structure are significantly affected by the doped chalcogen and its related oxidative state. Notably, upon heating or adding an acid, the selenium-doped NG or its oxide undergoes a selenium extrusion reaction to afford seco-HBC or HBC quantitatively, which can be treated as precursors of hydrocarbon HBCs.

RegraphGAN: A graph generative adversarial network model for dynamic network anomaly detection.

Due to the wide application of dynamic graph anomaly detection in cybersecurity, social networks, e-commerce, etc., research in this area has received increasing attention. Graph generative adversarial networks can be used in dynamic graph anomaly detection due to their ability to model complex data, but the original graph generative adversarial networks do not have a method to learn reverse mapping and require an expensive process in recovering the potential representation of a given input. Therefore, this paper proposes a novel graph generative adversarial network by adding encoders to map real data to latent space to improve the training efficiency and stability of graph generative adversarial network models, which is named RegraphGAN in this paper. And this paper proposes a dynamic network anomaly edge detection method by combining RegraphGAN with spatiotemporal coding to solve the complex dynamic graph data and the problem of attribute-free node information coding challenges. Meanwhile, anomaly detection experiments are conducted on six real dynamic network datasets, and the results show that the dynamic network anomaly detection method proposed in this paper outperforms other existing methods.

ATP-citrate lyase controls endothelial gluco-lipogenic metabolism and vascular inflammation in sepsis-associated organ injury.

Sepsis involves endothelial cell (EC) dysfunction, which contributes to multiple organ failure. To improve therapeutic prospects, elucidating molecular mechanisms of vascular dysfunction is of the essence. ATP-citrate lyase (ACLY) directs glucose metabolic fluxes to de novo lipogenesis by generating acetyl-Co-enzyme A (acetyl-CoA), which facilitates transcriptional priming via protein acetylation. It is well illustrated that ACLY participates in promoting cancer metastasis and fatty liver diseases. Its biological functions in ECs during sepsis remain unclear. We found that plasma levels of ACLY were increased in septic patients and were positively correlated with interleukin (IL)-6, soluble E-selectin (sE-selectin), soluble vascular cell adhesion molecule 1 (sVCAM-1), and lactate levels. ACLY inhibition significantly ameliorated lipopolysaccharide challenge-induced EC proinflammatory response in vitro and organ injury in vivo. The metabolomic analysis revealed that ACLY blockade fostered ECs a quiescent status by reducing the levels of glycolytic and lipogenic metabolites. Mechanistically, ACLY promoted forkhead box O1 (FoxO1) and histone H3 acetylation, thereby increasing the transcription of c-Myc (MYC) to facilitate the expression of proinflammatory and gluco-lipogenic genes. Our findings revealed that ACLY promoted EC gluco-lipogenic metabolism and proinflammatory response through acetylation-mediated MYC transcription, suggesting ACLY as the potential therapeutic target for treating sepsis-associated EC dysfunction and organ injury.

MALAT1 modulates trophoblast phenotype via miR-101-3p/VEGFA axis.

Preeclampsia is a potentially life-threatening condition that can arise due to poor placentation and consequent abnormal uterine spiral artery remodeling. Abnormal placentation, in turn, is associated with aberrant trophoblast cell proliferation and apoptosis. Here, we investigated the lncRNA MALAT1 in trophoblast proliferation during early-onset preeclampsia (ePE). MALAT1 levels were examined in placental tissue samples from ePE patients and control patients. The effects and underlying mechanism of MALAT1 on proliferation, migration, invasion and apoptosis were investigated in the first-trimester extravillous trophoblast HTR-8/SVneo cells and the human choriocarcinoma JAR cells. MALAT1 levels were decreased in the placental tissue samples of ePE patients compared with those of control patients, and the levels of MALAT1 were positively correlated with the neonate birth-weight. Knockdown of MALAT1 attenuated the cell viability, proliferation, migration, invasion and the cell cycle progression of trophoblasts, but promoted the apoptosis of trophoblasts. The MALAT1 knockdown promoted miR-101-3p upregulation and VEGFA downregulation. Inhibitor of miR-101-3p increased vascular endothelial growth factor A (VEGFA) expression, and miR-101-3p mimic inhibited VEGFA expression. Luciferase assays showed that miR-101-3p could bind to both MALAT1 and VEGFA. The MALAT1 knockdown-induced induction in the cell vitality and proliferation were attenuated by miR-101-3p inhibitor. We conclude that endogenous MALAT1 promotes proliferation, migration and invasion of trophoblasts by inhibiting the miR-101-3p expression and the subsequent VEGFAupregulation. The reduced MALAT1 level in placental tissue may be involved in the pathogenesis of the ePE.

Construction of hexabenzocoronene-based chiral nanographenes.

The past decade witnessed remarkable success in synthetic molecular nanographenes. Encouraged by the widespread application of chiral nanomaterials, the design, and construction of chiral nanographenes is a hot topic recently. As a classic nanographene unit, hexa-peri-hexabenzocoronene generally serves as the building block for nanographene synthesis. This review summarizes the representative examples of hexa-peri-hexabenzocoronene-based chiral nanographenes.

Phenylalanine promotes alveolar macrophage pyroptosis via the activation of CaSR in ARDS.

Acute respiratory distress syndrome (ARDS) is associated with high mortality rates in patients admitted to the intensive care unit (ICU) patients with overwhelming inflammation considered to be an internal cause. The authors' previous study indicated a potential correlation between phenylalanine levels and lung injury. Phenylalanine induces inflammation by enhancing the innate immune response and the release of pro-inflammatory cytokines. Alveolar macrophages (AMs) can respond to stimuli via synthesis and release of inflammatory mediators through pyroptosis, one form of programmed cell death acting through the nucleotide-binging oligomerization domain-like receptors protein 3 (NLRP3) signaling pathway, resulting in the cleavage of caspase-1 and gasdermin D (GSDMD) and the release of interleukin (IL) -1ß and IL-18, aggravating lung inflammation and injury in ARDS. In this study, phenylalanine promoted pyroptosis of AMs, which exacerbated lung inflammation and ARDS lethality in mice. Furthermore, phenylalanine initiated the NLRP3 pathway by activating the calcium-sensing receptor (CaSR). These findings uncovered a critical mechanism of action of phenylalanine in the context of ARDS and may be a new treatment target for ARDS.