Optical spin hall effect in exciton-polariton condensates in lead halide perovskite microcavities.

An exciton-polariton condensate is a hybrid light-matter state in the quantum fluid phase. The photonic component endows it with characters of spin, as represented by circular polarization. Spin-polarization can form stochastically for quasi-equilibrium exciton-polariton condensates at parallel momentum vector k|| ∼ 0 from bifurcation or deterministically for propagating condensates at k|| > 0 from the optical spin-Hall effect (OSHE). Here, we report deterministic spin-polarization in exciton-polariton condensates at k|| ∼ 0 in microcavities containing methylammonium lead bromide perovskite (CH3NH3PbBr3) single crystals under non-resonant and linearly polarized excitation. We observe two energetically split condensates with opposite circular polarizations and attribute this observation to the presence of strong birefringence, which introduces a large OSHE at k|| ∼ 0 and pins the condensates in a particular spin state. Such spin-polarized exciton-polariton condensates may serve not only as circularly polarized laser sources but also as effective alternatives to ultracold atom Bose-Einstein condensates in quantum simulators of many-body spin-orbit coupling processes.

CircCDYL2 bolsters radiotherapy resistance in nasopharyngeal carcinoma by promoting RAD51 translation initiation for enhanced homologous recombination repair.

BACKGROUND: Radiation therapy stands to be one of the primary approaches in the clinical treatment of malignant tumors. Nasopharyngeal Carcinoma, a malignancy predominantly treated with radiation therapy, provides an invaluable model for investigating the mechanisms underlying radiation therapy resistance in cancer. While some reports have suggested the involvement of circRNAs in modulating resistance to radiation therapy, the underpinning mechanisms remain unclear. METHODS: RT-qPCR and in situ hybridization were used to detect the expression level of circCDYL2 in nasopharyngeal carcinoma tissue samples. The effect of circCDYL2 on radiotherapy resistance in nasopharyngeal carcinoma was demonstrated by in vitro and in vivo functional experiments. The HR-GFP reporter assay determined that circCDYL2 affected homologous recombination repair. RNA pull down, RIP, western blotting, IF, and polysome profiling assays were used to verify that circCDYL2 promoted the translation of RAD51 by binding to EIF3D protein. RESULTS: We have identified circCDYL2 as highly expressed in nasopharyngeal carcinoma tissues, and it was closely associated with poor prognosis. In vitro and in vivo experiments demonstrate that circCDYL2 plays a pivotal role in promoting radiotherapy resistance in nasopharyngeal carcinoma. Our investigation unveils a specific mechanism by which circCDYL2, acting as a scaffold molecule, recruits eukaryotic translation initiation factor 3 subunit D protein (EIF3D) to the 5'-UTR of RAD51 mRNA, a crucial component of the DNA damage repair pathway to facilitate the initiation of RAD51 translation and enhance homologous recombination repair capability, and ultimately leads to radiotherapy resistance in nasopharyngeal carcinoma. CONCLUSIONS: These findings establish a novel role of the circCDYL2/EIF3D/RAD51 axis in nasopharyngeal carcinoma radiotherapy resistance. Our work not only sheds light on the underlying molecular mechanism but also highlights the potential of circCDYL2 as a therapeutic sensitization target and a promising prognostic molecular marker for nasopharyngeal carcinoma.

Mechanism of electroconvulsive therapy in schizophrenia: a bioinformatics analysis study of RNA-seq data.

OBJECTIVE: The molecular mechanism of electroconvulsive therapy (ECT) for schizophrenia remains unclear. The aim of this study was to uncover the underlying biological mechanisms of ECT in the treatment of schizophrenia using a transcriptional dataset. METHODS: The peripheral blood mRNA sequencing data of eight patients (before and after ECT) and eight healthy controls were analyzed by integrated co-expression network analysis and the differentially expressed genes were analyzed by cluster analysis. Gene set overlap analysis was performed using the hypergeometric distribution of phypfunction in R. Associations of these gene sets with psychiatric disorders were explored. Tissue-specific enrichment analysis, gene ontology enrichment analysis, and protein-protein interaction enrichment analysis were used for gene set organization localization and pathway analysis. RESULTS: We found the genes of the green-yellow module were significantly associated with the effect of ECT treatment and the common gene variants of schizophrenia ( P  = 0.0061; family-wise error correction). The genes of the green-yellow module are mainly enriched in brain tissue and mainly involved in the pathways of neurotrophin, mitogen-activated protein kinase and long-term potentiation. CONCLUSION: Genes associated with the efficacy of ECT were predominantly enriched in neurotrophin, mitogen-activated protein kinase and long-term potentiation signaling pathways.

Molecular Polaritons for Chemistry, Photonics and Quantum Technologies.

Molecular polaritons are quasiparticles resulting from the hybridization between molecular and photonic modes. These composite entities, bearing characteristics inherited from both constituents, exhibit modified energy levels and wave functions, thereby capturing the attention of chemists in the past decade. The potential to modify chemical reactions has spurred many investigations, alongside efforts to enhance and manipulate optical responses for photonic and quantum applications. This Review centers on the experimental advances in this burgeoning field. Commencing with an introduction of the fundamentals, including theoretical foundations and various cavity architectures, we discuss outcomes of polariton-modified chemical reactions. Furthermore, we navigate through the ongoing debates and uncertainties surrounding the underpinning mechanism of this innovative method of controlling chemistry. Emphasis is placed on gaining a comprehensive understanding of the energy dynamics of molecular polaritons, in particular, vibrational molecular polaritons─a pivotal facet in steering chemical reactions. Additionally, we discuss the unique capability of coherent two-dimensional spectroscopy to dissect polariton and dark mode dynamics, offering insights into the critical components within the cavity that alter chemical reactions. We further expand to the potential utility of molecular polaritons in quantum applications as well as precise manipulation of molecular and photonic polarizations, notably in the context of chiral phenomena. This discussion aspires to ignite deeper curiosity and engagement in revealing the physics underpinning polariton-modified molecular properties, and a broad fascination with harnessing photonic environments to control chemistry.

Mechanism of color change in Antarctic krill oil during storage.

Antarctic krill oil (AKO) is reddish-orange in color but undergoes changes during storage. To investigate the color deterioration and potential mechanisms involved, the changes in color, endogenous components (astaxanthin, fatty acids, and phospholipids), and reaction products (aldehydes, α-dicarbonyl compounds, and pyrroles) of AKO upon storage were determined. Although the visual color of AKO tended to darken upon storage, the colorimetric analysis and ultraviolet-visible spectrum analysis both indicated a fading in red and yellow due to the oxidative degradation of astaxanthin. During storage of AKO, lipid oxidation led to the formation of carbonyl compounds such as aldehydes and α-dicarbonyls. In addition, phosphatidylethanolamines (PEs) exhibited a faster loss rate than phosphatidylcholines. Moreover, hydrophobic pyrroles, the Maillard-like reaction products associated with primary amine groups in PEs accumulated. Therefore, it is suggested that the Maillard-like reaction between PEs and carbonyl compounds formed by lipid oxidation contributed to color darkening of AKO during storage.

Antiviral Effect of Extracellular Matrix Protein ABI3BP on Vesicular Stomatitis Virus and Its Mechanism: A Preliminary Study In Vitro.

Objective To explore the influence of extracellular matrix protein ABI-interactor 3-binding protein (ABI3BP) on vesicular stomatitis virus (VSV) genome replication and innate immune signaling pathway.Methods The small interfering RNA (siRNA) was transfected to knock down ABI3BP gene in human skin fibroblast BJ-5ta cells. VSV-green fluorescent protein (VSV-GFP)-infected cell model was established. The morphological changes and F-actin stress fiber formation were detected on ABI3BP knockdown cells by phalloidin immunofluorescence staining. The mRNA level of virus replication was detected by RT-qPCR in BJ-5ta cells after VSV-GFP infection; western blotting was performed to detect the changes in interferon regulatory factor 3 (IRF3) and TANK-binding kinase 1 (TBK1) phosphorylation levels.Results The VSV-GFP-infected BJ-5ta cell model was successfully established. Efficient knockdown of ABI3BP in BJ-5ta cells was achieved. Phalloidin immunofluorescence staining revealed structural rearrangement of intracellular F-actin after ABI3BP gene knockdown. Compared with the control group, the gene copy number of VSV-GFP in ABI3BP knockdown cells increased by 2.2 - 3.5 times (P<0.01) and 2.2 - 4.0 times (P<0.01) respectively when infected with VSV of multiplicity of infection 0.1 and 1. The expression of viral protein significantly increased in ABI3BP knockdown cells after virus infection. The activation of type-I interferon pathway, as determined by phosphorylated IRF3 and phosphorylated TBK1, was significantly decreased in ABI3BP knockdown cells after VSV-GFP infection.Conclusions Extracellular matrix protein ABI3BP plays an important role in maintaining the formation and rearrangement of actin structure. ABI3BP gene deletion promotes RNA virus replication, and ABI3BP is an important molecule that maintains the integrity of type I interferon pathway.

Neurogenetic underpinnings of nicotine use severity: Integrating the brain transcriptomes and GWAS variants via network approaches.

Our study focused on human brain transcriptomes and the genetic risks of cigarettes per day (CPD) to investigate the neurogenetic mechanisms of individual variation in nicotine use severity. We constructed whole-brain and intramodular region-specific coexpression networks using BrainSpan's transcriptomes, and the genomewide association studies identified risk variants of CPD, confirmed the associations between CPD and each gene set in the region-specific subnetworks using an independent dataset, and conducted bioinformatic analyses. Eight brain-region-specific coexpression subnetworks were identified in association with CPD: amygdala, hippocampus, medial prefrontal cortex (MPFC), orbitofrontal cortex (OPFC), dorsolateral prefrontal cortex, striatum, mediodorsal nucleus of the thalamus (MDTHAL), and primary motor cortex (M1C). Each gene set in the eight subnetworks was associated with CPD. We also identified three hub proteins encoded by GRIN2A in the amygdala, PMCA2 in the hippocampus, MPFC, OPFC, striatum, and MDTHAL, and SV2B in M1C. Intriguingly, the pancreatic secretion pathway appeared in all the significant protein interaction subnetworks, suggesting pleiotropic effects between cigarette smoking and pancreatic diseases. The three hub proteins and genes are implicated in stress response, drug memory, calcium homeostasis, and inhibitory control. These findings provide novel evidence of the neurogenetic underpinnings of smoking severity.

ITGB6 may promote proliferation and invasion in pancreatic cancer.

Introduction: The ITGB6 gene encoding a protein that can regulate the integrin αvß6 heterodimer protein expression in different status was shown to play an important role in multiple human cancers, such as brain cancer, colon cancer and oral cancer, and is related to clinical progression. This study aims to explore the function and the mechanism of the ITGB6 gene or protein in pancreatic cancer. Material and methods: We examined the expression of ITGB6 in pancreatic cancer using immunohistochemistry and analyzed the relationship between the expression of ITGB6 and the clinicopathologic features in pancreatic cancer patients. In addition, a bioinformatic method was used to analyze the ITGB6 mRNA level in pancreatic tumor tissues compared with normal pancreatic tissues and to analyze the correlation between high KIF23 expression and prognosis in pancreatic cancer patients. Moreover, colony formation assay, MTT assay, cell scratch, cell invasion and western blot assays in vitro and a xenograft mouse model in vivo were performed to analyze the effect of KIF23 on proliferation and invasion of pancreatic cancer cells. Results: Increased expression of ITGB6 was significantly correlated with poor clinical outcome in both our clinical data and TCGA data of pancreatic cancer. Furthermore, functional assays revealed that ITGB6 knockdown in vivo and in vitro might inhibit cancer cell proliferation and the ability of invasion or migration. Conclusions: Our data suggest that ITGB6 is associated with pancreatic cancer malignant progression. Hence, ITGB6 may serve as a potential target of pancreatic cancer for future research, and further study is needed.

Performance of the 2019 ACR/EULAR Classification Criteria for IgG4-Related Disease in a Large Chinese Cohort.

OBJECTIVE: The purpose of this research was to ascertain the effectiveness of the newly established criteria for classifying IgG4-related disease (IgG4-RD), as applied to a large Chinese cohort in real-world clinical settings. METHODS: Patient data were procured from the digital health records of 4 prominent academic hospitals. The criterion standard for identifying IgG4-RD patients was from a seasoned rheumatologist. The control group consisted of individuals with other ailments such as cancer, other forms of pancreatitis, infectious diseases, and illnesses that mimic IgG4-RD. RESULTS: A total of 605 IgG4-RD patients and 760 mimickers were available for analysis. The 2019 EULAR/ACR criteria have a sensitivity of 69.1% and a specificity of 90.9% in this large Chinese cohort. IgG4-RD had a greater proportion of males (55.89% vs 36.25%, p < 0.001), an older average age at diagnosis (54.91 ± 13.44 vs 48.91 ± 15.71, p < 0.001), more pancreatic (29.59% vs 6.12%, p < 0.001) and salivary gland (63.30% vs 27.50%, p < 0.001) involvement, and a larger number of organ involvement (3.431 ± 2.054 vs 2.062 ± 1.748, p < 0.001) compared with mimickers. CONCLUSIONS: The 2019 EULAR/ACR criteria are effective in classifying IgG4-RD in Chinese patients, demonstrating high specificity and moderate sensitivity.

Phase separation in DNA double-strand break response.

DNA double-strand break (DSB) is the most dangerous type of DNA damage, which may lead to cell death or oncogenic mutations. Homologous recombination (HR) and nonhomologous end-joining (NHEJ) are two typical DSB repair mechanisms. Recently, many studies have revealed that liquid-liquid phase separation (LLPS) plays a pivotal role in DSB repair and response. Through LLPS, the crucial biomolecules are quickly recruited to damaged sites with a high concentration to ensure DNA repair is conducted quickly and efficiently, which facilitates DSB repair factors activating downstream proteins or transmitting signals. In addition, the dysregulation of the DSB repair factor's phase separation has been reported to promote the development of a variety of diseases. This review not only provides a comprehensive overview of the emerging roles of LLPS in the repair of DSB but also sheds light on the regulatory patterns of phase separation in relation to the DNA damage response (DDR).

SOCS2 inhibits hepatoblastoma metastasis via downregulation of the JAK2/STAT5 signal pathway.

Metastasis of hepatoblastoma (HB) is a key factor that impairs the prognosis and treatment of children. The suppressor of cytokine signaling 2 (SOCS2) is a classical negative feedback protein that regulates cytokine signal transduction and has been known to be downregulated in several tumor, but the molecular mechanisms of its involvement in HB metastasis are unknown. We found that SOCS2 was a gene down-regulated in hepatoblastoma and associated with HB metastasis through bioinformatics. The qRT-PCR, Western blot and IHC showed that SOCS2 was significantly lower in HB tissues. Clinicopathological correlation analysis revealed that low expression of SOCS2 was significantly correlated with tumor metastasis (P = 0.046) and vascular invasion (P = 0.028), associated with poor prognosis. Overexpression of SOCS2 inhibited the migration and invasion of hepatoblastoma cells, while knockdown of SOCS2 expression promoted these malignant phenotypes. In vivo studies revealed overexpression of SOCS2 inhibited the formation of lung metastasis. Up-regulation of SOCS2 in HB cell inhibited EMT and JAK2/STAT5. Conversely, down-regulation of SOCS2 promoted EMT and JAK2/STAT5. The addition of the JAK2 inhibitor Fedratinib partially reversed the effects of si-SOCS2 on HB cells. SOCS2 may inhibit the migration and invasion of HB cells by inhibiting the JAK2/STAT5 signaling pathway. These results may provide guiding significance for the clinical treatment of HB.

CiRS-7 Enhances the Liquid-liquid Phase Separation of miRISC and Promotes DNA Damage Repair.

Noncoding RNAs have been found to play important roles in DNA damage repair, whereas the participation of circRNA remains undisclosed. Here, we characterized ciRS-7, a circRNA containing over 70 putative miR-7-binding sites, as an enhancer of miRISC condensation and DNA repair. Both in vivo and in vitro experiments confirmed the condensation of TNRC6B and AGO2, two core protein components of human miRISC. Moreover, overexpressing ciRS-7 largely increased the condensate number of TNRC6B and AGO2 in cells, while silencing ciRS-7 reduced it. Additionally, miR-7 overexpression also promoted miRISC condensation. Consistent with the previous report that AGO2 participated in RAD51-mediated DNA damage repair, the overexpression of ciRS-7 significantly promoted irradiation-induced DNA damage repair by enhancing RAD51 recruitment. Our results uncover a new role of circRNA in liquid-liquid phase separation and provide new insight into the regulatory mechanism of ciRS-7 on miRISC function and DNA repair.

Liquid-liquid phase separation in DNA double-strand breaks repair.

DNA double-strand breaks (DSBs) are the fatal type of DNA damage mostly induced by exposure genome to ionizing radiation or genotoxic chemicals. DSBs are mainly repaired by homologous recombination (HR) and nonhomologous end joining (NHEJ). To repair DSBs, a large amount of DNA repair factors was observed to be concentrated at the end of DSBs in a specific spatiotemporal manner to form a repair center. Recently, this repair center was characterized as a condensate derived from liquid-liquid phase separation (LLPS) of key DSBs repair factors. LLPS has been found to be the mechanism of membraneless organelles formation and plays key roles in a variety of biological processes. In this review, the recent advances and mechanisms of LLPS in the formation of DSBs repair-related condensates are summarized.

Silencing AHNAK promotes nasopharyngeal carcinoma progression by upregulating the ANXA2 protein.

PURPOSE: Nasopharyngeal carcinoma (NPC) is an aggressive head and neck disease with a high incidence of distant metastases. Enlargeosomes are cytoplasmic organelles marked by, desmoyokin/AHNAK. This study aimed to evaluate the expression of AHNAK in NPC and its effect on enlargeosomes and to investigate the correlation between AHNAK expression levels and clinical NPC patient characteristics. METHODS: Primary nasopharyngeal carcinoma (NPC) and NPC specimens were evaluated by analyzing public data, and immunohistochemistry. Systematic in vitro and in vivo experiments were performed using different NPC-derived cell lines and mouse models. RESULTS: In this study, we detected AHNAK and Annexin A2(ANXA2), a protein coating the surface of enlargeosomes, in NPC samples. We found that AHNAK was down-regulated. Down-regulation of AHNAK was associated with poor overall survival in NPC patients. Moreover, transcription factor FOSL1-mediated transcriptional repression was responsible for the low expression of AHNAK by recruiting EZH2. Whereas Annexin A2 was upregulated in human NPC tissues. Upregulation of Annexin A2 was associated with lymph node metastasis and distant metastasis in NPC patients. Functional studies confirmed that silencing of AHNAK enhanced the growth, invasion, and metastatic properties of NPC cells both in vitro and in vivo. In terms of mechanism, loss of AHNAK led to an increase of annexin A2 protein level in NPC cells. Silencing ANXA2 restored NPC cells' migrative and invasive ability upon loss of AHNAK. CONCLUSION: Here, we report AHNAK as a tumor suppressor in NPC, which may act through annexin A2 oncogenic signaling in enlargeosome, with potential implications for novel approaches to NPC treatment.

Nitric oxide synthase and its function in animal reproduction: an update.

Nitric oxide (NO), a free radical labile gas, is involved in the regulation of various biological functions and physiological processes during animal reproduction. Recently, increasing evidence suggests that the biological role and chemical fate of NO is dependent on dynamic regulation of its biosynthetic enzyme, three distinct nitric oxide synthase (NOS) according to their structure, location and function. The impact of NOS isoforms on reproductive functions need to be timely elucidated. Here, we focus on and the basic background and latest studies on the development, structure, importance inhibitor, location pattern, complex functions. Moreover, we summarize the exactly mechanisms which involved some cell signal pathways in the regulation of NOS with cellular and molecular level in the animal reproduction. Therefore, this growing research area provides the new insight into the important role of NOS male and female reproduction system. It also provides the treatment evidence on targeting NOS of reproductive regulation and diseases.

miR-181b-5p/SOCS2/JAK2/STAT5 axis facilitates the metastasis of hepatoblastoma.

Introduction: Hepatoblastoma (HB) is a malignant liver tumor predominantly found in children and tumor metastasis is one of the main causes of poor prognosis in affected patients. The precise molecular mechanisms responsible for HB metastasis remain incompletely understood. However, there is evidence suggesting a connection between the dysregulation of microRNAs (miRNAs) and the progression of tumor metastasis in HB. Methods: The study utilized weighted gene co-expression network analysis (WGCNA) to analyze a miRNA microarray dataset of HB. The expression of miR-181b-5p in HB tissues and cells was detected using quantitative real-time PCR. The impact of miR-181b-5p on the metastatic capacity of HB was evaluated through scratch and Transwell assays. The effects of exogenously expressing miR-181b on the metastatic phenotypes of HB cells were evaluated in vivo. Furthermore, a luciferase reporter assay was performed to validate a potential target of miR-181b-5p in HB. Results: We found that miR-181b-5p was highly expressed in HB tissues and HB cell lines. Overexpression of miR-181b enhanced scratch healing, cell migration, and invasion abilities in vitro, as well as enhancing HB lung metastasis potential in vivo. Dual-luciferase reporter assays showed that Suppressor Of Cytokine Signaling 2 (SOCS2) was a direct target of miR-181b. The overexpression of miR-181b resulted in the suppression of SOCS2 expression, subsequently activating the epithelial-mesenchymal transition and JAK2/STAT5 signaling pathways. The rescue experiment showed that SOCS2 overexpression attenuated the effects of miR-181b on HB cells. Conclusion: Our study showed that miR-181b promotes HB metastasis by targeting SOCS2 and may be a potential therapeutic target for HB.

LncRNA-mRNA coexpression analysis reveals distinct pathogenic mechanisms for subtypes of congenital biliary dilatation.

BACKGROUND/PURPOSE: Congenital biliary dilatation (CBD) is a bile duct malformation often associated with pancreaticobiliary maljunction. Different subtypes of CBD have been noted for clinical differences, but their pathogenic mechanisms are unclear. METHODS: To elucidate the genetic basis of CBD, we performed lncRNA and mRNA sequencing and bioinformatic analysis on 18 cystic and 18 fusiform CBD samples. RESULTS: We identified differentially expressed mRNAs and lncRNAs between the two types of CBD, and constructed coexpression modules that correlated with clinical characteristics of CBD using weighted gene coexpression network analysis. We found that the brown module was the highest positive correlation with fusiform CBD (R = 0.67, p = 7.9e-6) and contained the most genes. We then built a lncRNA-mRNA coexpression network to identify potential target genes of lncRNAs in CBD, and a protein-protein interaction network to investigate the hub genes from the target genes and the brown module. Finally, we performed enrichment analyses and found differences between cystic and fusiform CBD in hepatobiliary system development, liver and pancreas development involving hub genes ONECUT1 and HNF1B that could be regulated by corresponding lncRNAs. CONCLUSION: Our study suggests that lncRNAs may modulate pancreaticobiliary duct development differently in cystic and fusiform CBD, providing new insights for etiology studies and clinical treatment.