When IGF-1 Meets Metabolic Inflammation and Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder associated with insulin resistance (IR) and hyperandrogenaemia (HA). Metabolic inflammation (MI), characterized by a chronic low-grade inflammatory state, is intimately linked with chronic metabolic diseases such as IR and diabetes and is also considered an essential factor in the development of PCOS. Insulin-like growth factor 1 (IGF-1) plays an essential role in PCOS pathogenesis through its multiple functions in regulating cell proliferation metabolic processes and reducing inflammatory responses. This review summarizes the molecular mechanisms by which IGF-1, via MI, participates in the onset and progression of PCOS, aiming to provide insights for studies and clinical treatment of PCOS.

Multifunctional Phosphor with High-Efficient Near-Infrared Emission Based on Antimony-Zinc Halides.

Metal halide-based broadband near-infrared (NIR) luminescent materials face problems such as complicated preparation, high cost, low photoluminescence quantum yield, and high excitation energy. Here, incorporating Sb3+ and Br- into (C20H20P)2ZnCl4 crystals allowed for the achievement of efficient broadband near-infrared emission under 400 nm excitation while maintaining satisfactory environmental and thermal stability. The compounds exhibit a broad range of emission bands from 550 to 1050 nm, with a photoluminescence quantum yield of 93.57%. This is a groundbreaking achievement for organic-inorganic hybrid metal halide NIR luminescent materials. The near-infrared emission is suggested to originate from [SbX5]2-, as supported by the femtosecond transient absorption spectra and density-functional theory calculations. This phosphor-based NIR LEDs successfully demonstrate potential applications in night vision, medical imaging, information encryption, and anticounterfeiting.

Photon-carrier-spin coupling in a one-dimensional Ni(II)-doped ZnTe nanostructure.

Transition metal (TM) ion doping in II-VI semiconductors can produce exciton magnetic polarons (EMPs) and localized EMPs containing longitudinal optical (LO) phonon coupling, which will be discussed in this paper. TM ion doping in II-VI semiconductors for a dilute magnetic semiconductor show emission via magnetic polarons (MPs) together with hot carrier effects that need to be understood via its optical properties. The high excitation power that is responsible for hot carrier effects suppresses the charge trapping effect in low exciton binding energy (8.12 meV) semiconductors, even at room temperature (RT). The large polaron radius exhibits strong interaction between the carrier and MP, resulting in anharmonicity effects, in which the side-band energy overtone to LO phonons. The photon-like polaritons exhibit polarized spin interactions with LO phonons that show strong spin-phonon polaritons at RT. The temperature-dependent photoluminescence spectra of Ni-doped ZnTe show free excitons (FX) and FXs interacting with 2LO phonon-spin interactions, corresponding to3T1(3F) →1T1(1G) and EMP peaks with ferromagnetically coupled Ni ions at3T1(3F) →1E(1G). In addition, other d-d transitions of single Ni ions (600-900 nm) appear at the low-energy side. RT energy shifts of 14-38 meV are observed due to localized states with density-of-states tails extending far into the bandgap-related spin-induced localization at the valence band. These results show spin-spin magnetic coupling and spin-phonon interactions at RT that open up a more realistic new horizon of optically controlled dilute magnetic semiconductor applications.

Immune checkpoint inhibitors in colorectal cancer: limitation and challenges.

Colorectal cancer exhibits a notable prevalence and propensity for metastasis, but the current therapeutic interventions for metastatic colorectal cancer have yielded suboptimal results. ICIs can decrease tumor development by preventing the tumor's immune evasion, presenting cancer patients with a new treatment alternative. The increased use of immune checkpoint inhibitors (ICIs) in CRC has brought several issues. In particular, ICIs have demonstrated significant clinical effectiveness in patients with MSI-H CRC, whereas their efficacy is limited in MSS. Acquired resistance can still occur in patients with a positive response to ICIs. This paper describes the efficacy of ICIs currently in the clinical treatment of CRC, discusses the mechanisms by which acquired resistance occurs, primarily related to loss and impaired presentation of tumor antigens, reduced response of IFN-λ and cytokine or metabolic dysregulation, and summarizes the incidence of adverse effects. We posit that the future of ICIs hinges upon the advancement of precise prediction biomarkers and the implementation of combination therapies. This study aims to elucidate the constraints associated with ICIs in CRC and foster targeted problem-solving approaches, thereby enhancing the potential benefits for more patients.

Investigating gene signatures associated with immunity in colon adenocarcinoma to predict the immunotherapy effectiveness using NFM and WGCNA algorithms.

Colon adenocarcinoma (COAD), a frequently encountered and highly lethal malignancy of the digestive system, has been the focus of intensive research regarding its prognosis. The intricate immune microenvironment plays a pivotal role in the pathological progression of COAD; nevertheless, the underlying molecular mechanisms remain incompletely understood. This study aims to explore the immune gene expression patterns in COAD, construct a robust prognostic model, and delve into the molecular mechanisms and potential therapeutic targets for COAD liver metastasis, thereby providing critical support for individualized treatment strategies and prognostic evaluation. Initially, we curated a comprehensive dataset by screening 2600 immune-related genes (IRGs) from the ImmPort and InnateDB databases, successfully obtaining a rich data resource. Subsequently, the COAD patient cohort was classified using the non-negative matrix factorization (NMF) algorithm, enabling accurate categorization. Continuing on, utilizing the weighted gene co-expression network analysis (WGCNA) method, we analyzed the top 5000 genes with the smallest p-values among the differentially expressed genes (DEGs) between immune subtypes. Through this rigorous screening process, we identified the gene modules with the strongest correlation to the COAD subpopulation, and the intersection of genes in these modules with DEGs (COAD vs COAD vs Normal colon tissue) is referred to as Differentially Expressed Immune Genes Associated with COAD (DEIGRC). Employing diverse bioinformatics methodologies, we successfully developed a prognostic model (DPM) consisting of six genes derived from the DEIGRC, which was further validated across multiple independent datasets. Not only does this predictive model accurately forecast the prognosis of COAD patients, but it also provides valuable insights for formulating personalized treatment regimens. Within the constructed DPM, we observed a downregulation of CALB2 expression levels in COAD tissues, whereas NOXA1, KDF1, LARS2, GSR, and TIMP1 exhibited upregulated expression levels. These genes likely play indispensable roles in the initiation and progression of COAD and thus represent potential therapeutic targets for patient management. Furthermore, our investigation into the molecular mechanisms and therapeutic targets for COAD liver metastasis revealed associations with relevant processes such as fat digestion and absorption, cancer gene protein polysaccharides, and nitrogen metabolism. Consequently, genes including CAV1, ANXA1, CPS1, EDNRA, and GC emerge as promising candidates as therapeutic targets for COAD liver metastasis, thereby providing crucial insights for future clinical practices and drug development. In summary, this study uncovers the immune gene expression patterns in COAD, establishes a robust prognostic model, and elucidates the molecular mechanisms and potential therapeutic targets for COAD liver metastasis, thereby possessing significant theoretical and clinical implications. These findings are anticipated to offer substantial support for both the treatment and prognosis management of COAD patients.

Liensinine sensitizes colorectal cancer cells to oxaliplatin by targeting HIF-1α to inhibit autophagy.

BACKGROUND: Oxaliplatin is the most common chemotherapeutic agent for patients with colorectal cancer. However, its anti-cancer efficacy is restricted by drug resistance occurring through several mechanisms, including autophagy. Liensinine exerts a considerable anti-tumor effect and can regulate autophagy. Inhibition of autophagy is a strategy to reverse resistance to oxaliplatin. The aim of this study was to check if liensinine can enhance the therapeutic efficacy of oxaliplatin in colorectal cancer and if so, elucidate its mechanism. METHODS: Two colorectal cancer cell lines, HCT116 and LoVo, and one normal intestinal epithelial cell, NCM-460 were used for in vitro experiments. Cell Counting Kit-8 (CCK-8), colony formation, and flow cytometry assays were used to evaluate the cytotoxicity of liensinine and oxaliplatin. Network pharmacology analysis and Human XL Oncology Array were used to screen targets of liensinine. Transfections and autophagy regulators were used to confirm these targets. The relationship between the target and clinical effect of oxaliplatin was analyzed. Patient-derived xenograft (PDX) models were used to validate the effects of liensinine and oxaliplatin. RESULTS: CCK-8 and colony formation assays both showed that the combination treatment of liensinine and oxaliplatin exerted synergistic effects. Results of the network pharmacology analysis and Human XL Oncology Array suggested that liensinine can inhibit autophagy by targeting HIF-1α/eNOS. HIF-1α was identified as the key factor modulated by liensinine in autophagy and induces resistance to oxaliplatin. HIF-1α levels in tumor cells and prognosis for FOLFOX were negatively correlated in clinical data. The results from three PDX models with different HIF-1α levels showed their association with intrinsic and acquired resistance to oxaliplatin in these models, which could be reversed by liensinine. CONCLUSIONS: Research on the relationship between HIF-1α levels and the clinical effect of oxaliplatin is lacking, and whether liensinine regulates HIF-1α is unknown. Our findings suggest that liensinine overcomes the resistance of colorectal cancer cells to oxaliplatin by suppressing HIF-1α levels to inhibit autophagy. Our findings can contribute to improving prognosis following colorectal cancer therapy.

The role of long non-coding RNA in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a prevalent liver malignancy with complex etiology and generally poor prognosis. Recently, long non-coding RNAs (lncRNAs), non-protein-coding RNA molecules exceeding 200 nucleotides, have emerged as pivotal players in HCC, influencing its initiation, progression, invasion, and metastasis. These lncRNAs modulate gene expression at epigenetic, transcriptional, and post-transcriptional levels, actively participating in the pathological and physiological processes of HCC. Understanding the intricate relationship between lncRNAs and HCC is important for improving prognosis and reducing mortality. This review summarizes advancements in elucidating the role of lncRNAs in HCC pathogenesis.

Sb3+-Doped Indium-Based Metal Halide (Gua)3InCl6 with Efficient Yellow Emission.

In recent years, low-dimensional organic-inorganic hybrid metal halides (OIHMHs) have shown excellent photophysical properties due to their quantum structure, adjustable energy levels, and energy transfer between inorganic and organic components, which have attracted extensive attention from researchers. Herein, we synthesize a zero-dimensional (0D) OIHMH, Sb3+:(Gua)3InCl6, by introducing Sb3+ into (Gua)3InCl6, which undergoes a significant enhancement of the emission peak at 580 nm with the photoluminescence quantum yield (PLQY) boosted from 17.86 to 95.72% when excited at 340 nm. This boost in photoluminescence of the doped sample was studied by combining ultrafast femtosecond transient absorption, temperature-dependent photoluminescence (PL) spectra, and density functional theory (DFT) calculation, revealing the process of self-trapped exciton (STE) recombination to emit light at both Sb and In sites in this 0D structure simultaneously. This material with the lowest dark STE level at the In site for emission in the undoped sample can amazingly yield very strong emission in the doped sample, which has never been observed before. Finally, we tested its application in a photoelectric device. This work not only helps to gain a deeper understanding of the formation of STEs in In-based halides but also plays a certain guiding role in the design of new luminescent materials.

Pooled CRISPR Screening Identifies P-Bodies as Repressors of Cancer Epithelial-Mesenchymal Transition.

Epithelial-mesenchymal transition (EMT) is a fundamental cellular process frequently hijacked by cancer cells to promote tumor progression, especially metastasis. EMT is orchestrated by a complex molecular network acting at different layers of gene regulation. In addition to transcriptional regulation, posttranscriptional mechanisms may also play a role in EMT. Here, we performed a pooled CRISPR screen analyzing the influence of 1,547 RNA-binding proteins on cell motility in colon cancer cells and identified multiple core components of P-bodies (PB) as negative modulators of cancer cell migration. Further experiments demonstrated that PB depletion by silencing DDX6 or EDC4 could activate hallmarks of EMT thereby enhancing cell migration in vitro as well as metastasis formation in vivo. Integrative multiomics analysis revealed that PBs could repress the translation of the EMT driver gene HMGA2, which contributed to PB-meditated regulation of EMT. This mechanism is conserved in other cancer types. Furthermore, endoplasmic reticulum stress was an intrinsic signal that induced PB disassembly and translational derepression of HMGA2. Taken together, this study has identified a function of PBs in the regulation of EMT in cancer. SIGNIFICANCE: Systematic investigation of the influence of posttranscriptional regulation on cancer cell motility established a connection between P-body-mediated translational control and EMT, which could be therapeutically exploited to attenuate metastasis formation.

Autophagy in Disease Onset and Progression.

Autophagy is a biological phenomenon whereby components of cells can self-degrade using autophagosomes. During this process, cells can clear dysfunctional organelles or unwanted elements. Autophagy can recycle unnecessary biomolecules into new components or sometimes, even destroy the cells themselves. This cellular process was first observed in 1962 by Keith R. Porter et al. Since then, autophagy has been studied for over 60 years, and much has been learned on the topic. Nevertheless, the process is still not fully understood. It has been proven, for example, that autophagy can be a positive force for maintaining good health by removing older or damaged cells. By contrast, autophagy is also involved in the onset and progression of various conditions caused by pathogenic infections. These diseases generally involve several important organs in the human body, including the liver, kidney, heart, and central nervous system. The regulation of the defects of autophagy defects may potentially be used to treat some diseases. This review comprehensively discusses recent research frontiers and topics of interest regarding autophagy-related diseases.

Resonance-enhanced excitation and relaxation dynamics of coherent phonons in Fe1.14Te.

Lattice dynamics plays a significant role in manipulating the unique physical properties of materials. In this work, femtosecond transient optical spectroscopy is used to investigate the generation mechanism and relaxation dynamics of coherent phonons in Fe1.14Te-a parent compound of chalcogenide superconductors. The reflectivity time series consist of the exponential decay component due to hot carriers and damped oscillations caused by the A1g phonon vibration. The vibrational frequency and dephasing time of the A1g phonons are obtained as a function of temperature. With increasing temperature, the phonon frequency decreases and can be well described with the anharmonicity model. Dephasing time is independent of temperature, indicating that the phonon dephasing is dominated by phonon-defect scattering. The impulsive stimulated Raman scattering mechanism is responsible for the coherent phonon generation. Owing to the resonance Raman effect, the maximum photosusceptibility of the A1g phonons occurs at 1.590 eV, corresponding to an electronic transition in Fe1.14Te.

Potential therapeutic strategies for quercetin targeting critical pathological mechanisms associated with colon adenocarcinoma and COVID-19.

Patients with colon adenocarcinoma (COAD) are at a higher probability of infection with COVID-19 than healthy individuals. However, there is no globally accepted treatment protocol for patients with COAD/COVID-19. Quercetin has been found to have significant antitumor, antiviral and anti-inflammatory effects in several studies. Therefore, this study sought to evaluate the potential of quercetin as the agent for COAD/COVID-19 and to explore its mechanisms. We used bioinformatics algorithms to obtain COAD/COVID-19-related genes (CCRG) from COAD-related transcriptome data and COVID-related transcriptome sequencing data, and used these genes to construct a COAD prognostic model. We intersected the CCRG with the therapeutic target genes of quercetin and obtained a total of 105 genes (potential target genes of quercetin for the treatment of COAD/COVID-19). By constructing a protein-protein interaction (PPI) network, we ascertained FOS, NFKB1, NFKB1A, JUNB, and JUN as possible core target genes of quercetin for the treatment of COAD/COVID-19. Bioinformatic analysis of these 105 genes revealed that the mechanisms for quercetin the treatment of COAD/COVID-19 may be associated with oxidative stress, apoptosis, anti-inflammatory, immune, anti-viral and multiple pathways containing IL-17, TNF, HIF-1. In this study, we constructed a prognostic model of COAD/COVID19 patients by using CCRG and elucidated for the first time the potential target genes and molecular mechanisms of quercetin for the treatment of COAD/COVID-19, which may benefit the clinical treatment of COAD/COVID-19 patients. However, no clinical trials have yet been conducted to further validate the findings, but this will be the future direction of our research.

Gene editing monkeys: Retrospect and outlook.

Animal models play a key role in life science research, especially in the study of human disease pathogenesis and drug screening. Because of the closer proximity to humans in terms of genetic evolution, physiology, immunology, biochemistry, and pathology, nonhuman primates (NHPs) have outstanding advantages in model construction for disease mechanism study and drug development. In terms of animal model construction, gene editing technology has been widely applied to this area in recent years. This review summarizes the current progress in the establishment of NHPs using gene editing technology, which mainly focuses on rhesus and cynomolgus monkeys. In addition, we discuss the limiting factors in the applications of genetically modified NHP models as well as the possible solutions and improvements. Furthermore, we highlight the prospects and challenges of the gene-edited NHP models.

The SWI/SNF chromatin remodeling factor DPF3 regulates metastasis of ccRCC by modulating TGF-ß signaling.

DPF3, a component of the SWI/SNF chromatin remodeling complex, has been associated with clear cell renal cell carcinoma (ccRCC) in a genome-wide association study. However, the functional role of DPF3 in ccRCC development and progression remains unknown. In this study, we demonstrate that DPF3a, the short isoform of DPF3, promotes kidney cancer cell migration both in vitro and in vivo, consistent with the clinical observation that DPF3a is significantly upregulated in ccRCC patients with metastases. Mechanistically, DPF3a specifically interacts with SNIP1, via which it forms a complex with SMAD4 and p300 histone acetyltransferase (HAT), the major transcriptional regulators of TGF-ß signaling pathway. Moreover, the binding of DPF3a releases the repressive effect of SNIP1 on p300 HAT activity, leading to the increase in local histone acetylation and the activation of cell movement related genes. Overall, our findings reveal a metastasis-promoting function of DPF3, and further establish the link between SWI/SNF components and ccRCC.

When 3D genome technology meets viral infection, including SARS-CoV-2.

Mammalian chromosomes undergo varying degrees of compression to form three-dimensional genome structures. These three-dimensional structures undergo dynamic and precise chromatin interactions to achieve precise spatial and temporal regulation of gene expression. Most eukaryotic DNA viruses can invade their genomes into the nucleus. However, it is still poorly understood how the viral genome is precisely positioned after entering the host cell nucleus to find the most suitable location and whether it can specifically interact with the host genome to hijack the host transcriptional factories or even integrate into the host genome to complete its transcription and replication rapidly. Chromosome conformation capture technology can reveal long-range chromatin interactions between different chromosomal sites in the nucleus, potentially providing a reference for viral DNA-host chromatin interactions. This review summarized the research progress on the three-dimensional interaction between virus and host genome and the impact of virus integration into the host genome on gene transcription regulation, aiming to provide new insights into chromatin interaction and viral gene transcription regulation, laying the foundation for the treatment of infectious diseases.

Clinical Significance of Serum Haptoglobin and Protein Disulfide-Isomerase A3 in the Screening, Diagnosis, and Staging of Colorectal Cancer.

Objective: This study aims to explore the clinical significance of haptoglobin (HP) and protein disulfide-isomerase A3 (PDIA3) in human serum in the screening, diagnosis and staging of colorectal cancer (CRC), and to provide novel screening approaches featuring high specificity, sensitivity, and accuracy for early screening and diagnosis of clinical colorectal cancer. Methods: 88, 77, and 36 blood specimens were respectively harvested from colorectal cancer patients, colorectal polyp patients, and normal subjects (the health examination) who requested medical assistance from our hospital between Oct2019 and February 2022. The serum contents of HP and PDIA3 in each sample were determined through an enzyme linked immunosorbent assay (ELISA). This step was taken to analyze the differences among different specimen groups in terms of the serum contents of HP and PDIA3, to analyze the relationships between the expression levels of HP and PDIA3 and the pathological characteristics of colorectal cancer, and to explore the critical role of HP and PDIA3 in the screening, diagnosis, and staging of colorectal cancer. Results: Serum contents of HP and PDIA3 were higher in colorectal cancer patients, with statistical differences (p < 0.05), than those in the colonic polyp patients and healthy subjects. Receiver operating characteristic (ROC) curve demonstrated that the cut-offs of HP and PDIA3 serum contents indicating colorectal cancer were 149 ug/ml and 66 ng/ml respectively. The individually and jointly tested AUCs of HP (0.802) and PDIA3 (0.727) were higher than those of serum CEA and CA199, the sensitivity and specificity of HP were 64.8 and 91.2%, the sensitivity and specificity of PDIA3 were 65.9 and 71.7%. Moreover, the contents of HP and PDIA3 increased alongside disease progression, with differences (p < 0.05). Conclusion: Our research indicated that joint testing of HP and PDIA3 was of reference value for progressive stage and reliable biological indicators of colorectal cancer screening.

Puerarin: A Potential Therapeutic for Colon Adenocarcinoma (COAD) Patients Suffering From SARS-CoV-2 Infection.

Patients with colonic adenocarcinoma (COAD) are at relatively high risk of SARS-CoV-2 infection. However, there is a lack of medical strategies to treat COVID-19/COAD comorbidity. Puerarin, a natural product, is a known antiviral, antitumor, and immunomodulatory effect. Therefore, we hypothesised that puerarin could be used to treat COVID-19/COAD patients. Based on network pharmacology and bioinformatics analysis, the potential targets and pharmacological mechanisms of puerarin in COVID-19/COAD were identified. By intersecting therapeutic target genes for puerarin, COVID-19-related genes and COAD-related genes, 42 target genes of puerarin that could potentially treat COVID-19/COAD comorbidity were obtained. By using the 42 potential target genes to construct the protein-protein interaction (PPI) network, we obtained five core target genes, namely RELA, BCL2, JUN, FOS, and MAPK1. The results of bioinformatics analysis revealed that puerarin could be able to treat COVID-19/COAD comorbidity through apoptosis, antiviral, antioxidant, NF-κB signaling pathway, MAPK signaling pathway, IL-17 signaling pathway, TNF signaling pathway, and HIF-1 signaling pathway etc. This study found that puerarin has the potential to treat COVID-19/COAD patients and that the therapeutic target genes obtained in the study may provide clues for the treatment of COVID19/COAD comorbidity.

Puerarin: A Potential Therapeutic for SARS-CoV-2 and Hantavirus Co-Infection.

Patients with Hantavirus-caused epidemic hemorrhagic fever (EHF) are at risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there is currently no validated EHF/SARS-CoV-2 strategy. Several studies have recently shown Puerarin, a natural product, has potent antiviral properties. The goal of present study was to determine the mechanism of puerarin in patients with EHF/COVID-19. We use network pharmacology and bioinformatics to investigate the possible pharmacological targets, bioactivities, and molecular mechanisms of puerarin in the treatment of patients with EHF/SARS-CoV-2. The study investigated the pathogenesis of COVID-19 and EHF and the signaling pathway impacted by puerarin. 68 common genes linked to puerarin and EHF/SARS-CoV-2 were discovered during the investigation. By using protein-protein interaction (PPI) network, we identified RELA, JUN, NF-B1, NF-B2, and FOS as potential therapeutic targets. The bioactivity and signaling pathways of puerarin have also been demonstrated in the treatment of EHF and COVID-19. According to present study, puerarin could reduce excessive immune responses and inflammation through the NF-B, TNF, and HIF-1 signaling pathways. This study explored the potential therapeutic targets and mechanisms of Puerarin in the treatment of EHF/COVID-19.

Hot carrier dynamics of BiTeI with large Rashba spin splitting.

We present a time-resolved ultrafast optical spectroscopy study on BiTeI, a noncentrosymmetric semiconductor with large spin-orbit splitting. By tuning the pump photon energy, hot carriers can be excited into different energy bands, and the hot carriers decay dynamics are measured. The hot carriers excited by an 1.544 eV photon induce a positive differential reflectivity following a single exponential decay, while the hot carriers excited by an 1.651 eV photon show a negative reflectivity following two exponential decays, i.e., the hot carriers excited by 1.544 eV and 1.651 eV photons show different decay dynamics. We also investigate hot carrier dynamics in each Rashba splitting band at the 1.544 eV and 1.651 eV photon pump, and there is no difference in hot carrier decay between the left and right Rashba splitting bands for both cases.