Polysulfide Anions [Sx]2- (x = 2, 3, 4, 5): Promising Functional Building Units for Infrared Nonlinear Optical Materials.

Infrared nonlinear optical (IR NLO) materials play significant roles in laser technology. The novel functional building units (FBUs) are of great importance in constructing NLO materials with strong second harmonic generation (SHG). Herein, polysulfide anion [Sx]2- (x = 2, 3, 4, 5) units are investigated on NLO-related properties and structure-performance relationships. Theoretical calculations uncover that the [Sx]2- (x = 2, 3, 4, 5) units are potential IR NLO FBUs with large polarizability anisotropy (δ), hyperpolarizability (ß) and wide HOMO-LUMO gap. Fourteen crystals including [Sx]2- (x = 2, 3, 4, 5) units are calculated and analyzed. The results show that these units can result in a wide IR transmittance range, significant SHG effects, wide band gap Eg (Na2S4: Eg = 3.09 eV), and large birefringence Δn [BaS3 (P21212): Δn = 0.70]. More importantly, it is highlighted that the crystal materials including with [Sx]2- (x = 2, 3, 4, 5) groups are good candidates for the exploration of the outstanding IR NLO materials.

Eu3+-Directed Supramolecular Metallogels with Reversible Quadruple-Stimuli Response Behaviors.

Smart luminescent materials that have the ability to reversibly adapt to external environmental stimuli and possess a wide range of responses are continually emerging, which place higher demands on the means of regulation and response sites. Here, europium ions (Eu3+)-directed supramolecular metallogels are constructed by orthogonal self-assembly of Eu3+ based coordination interactions and hydrogen bonding. A new organic ligand (L) is synthesized, consisting of crown ethers and two flexible amide bonds-linked 1,10-phenanthroline moieties to coordinate with Eu3+. Synergistic intermolecular hydrogen bonding in L and Eu3+-L coordination bonding enable Eu3+ and L to self-assemble into shape-persistent 3D coordination metallogels in MeOH solution. The key to success is the utilization of crown ethers, playing dual roles of acting both as building blocks to build L with C2-symmetrical structure, and as the ideal monomer for increasing the energy transfer from L to Eu3+'s excited state, thus maintaining the excellent luminescence of metallogels. Interestingly, such assemblies show K+, pH, F-, and mechano-induced reversible gel-sol transitions and tunable luminescence properties. Above findings are useful in the studies of molecular switches, dynamic assemblies, and smart luminescent materials.

Analysis of Associated Factors, Construction, and Application of a Predictive Model for Lymph Node Metastasis in Colorectal Cancer.

Background: In colorectal cancer (CRC) , understanding lymph node metastasis (LNM) is critical for effective treatment. Better approaches are required for identifying and assessing the risk contributions of factors influencing lymph node metastasis in colorectal cancer. Objective: This study aims to analyze factors associated with LNM in CRC and develop a risk prediction model. Methods: A retrospective cohort study was conducted and a total of 181 CRC patients admitted between March 2020 and April 2023 were selected as research participants. Among them, 47 patients developed LNM, while the remaining 134 did not. Clinical data, including age, sex, pathological stages, were collected. Logistic regression was employed to identify factors influencing LNM in CRC, forming the basis for constructing a risk model. The diagnostic efficiency of this model was assessed through receiver operating characteristic (ROC) curves. Results: Tumor nodules and histological types showed no correlation with LNM in CRC (P > .05). However, pathological staging, vascular and neural invasion, use of VEGF inhibitors, and preoperative CEA were identified as independent risk factors for LNM in CRC (P < .05). The established model demonstrated a good fit with the observations. ROC curve analysis indicated an area under the curve (AUC) of 0.884 for predicting LNM in CRC, signifying excellent predictive performance. Conclusions: The risk model, formulated on factors associated with LNM in CRC, serves as a efficient tool in assessing the probability of LNM. It provides invaluable insights that can significantly enhance clinical approaches to the diagnosis and treatment of CRC in the future.

NaCl·CH4N2O·H2O: An Organic-Inorganic Hybrid Ultraviolet Nonlinear Optical Crystal with Optimized Comprehensive Properties.

Ultraviolet (UV) nonlinear optical (NLO) crystals are a vital component in laser systems to modulate frequency. Organic groups have the advantages of easy synthesis, structural diversity, and large hyperpolarizations (ß), which can be combined with inorganic groups to form unique organic-inorganic hybrid NLO crystal materials. Herein, a urea-containing crystal NaCl·CH4N2O·H2O is screened out and large-size crystals have been grown by a simple aqueous solution method. Compared with most reported organic-inorganic hybrid NLO materials, it has optimized comprehensive properties including a large SHG effect of 1.53 × KDP, a moderate birefringence (0.084@1064 nm), and a short UV cutoff edge of 209 nm. First-principles studies reveal that the dominant contributor to the linear and nonlinear optical properties is the urea molecule.

ATM inhibitor KU-55933 induces apoptosis and inhibits motility by blocking GLUT1-mediated glucose uptake in aggressive cancer cells with sustained activation of Akt.

Enhanced glucose uptake is coupled with elevated aerobic glycolysis (the Warburg effect) in cancer cells and is closely correlated with increased tumor aggressiveness and poor prognosis. We previously discovered that ATM, a protein kinase deficient in Ataxia-telangiectasia (A-T) disease, is an insulin-responsive protein that participates in insulin-mediated glucose uptake in muscle cells by stimulating glucose transporter 4 (GLUT4) translocation. However, the role of ATM in glucose uptake and tumorigenesis of cancer cells is unclear. In the present study, we found that aggressive breast and prostate cancer cell lines with overactivated Akt activity exhibit enhanced glucose uptake and GLUT1 translocation upon insulin treatment, and KU-55933, a specific inhibitor of ATM, inhibits insulin-mediated glucose uptake by blocking translocation of GLUT1 to the cell surface. KU-55933 also inhibits aerobic glycolysis and ATP production in these cells. Moreover, KU-55933 induces apoptosis and inhibits motility of cancer cells by inhibiting glucose uptake. Our results showed that while high concentration of glucose and insulin promote the expression of a mesenchymal biomarker (vimentin) in these cancer cells, KU-55933 strongly inhibits its expression as well as epithelial to mesenchymal transition. The roles of ATM in stimulating glucose uptake, glycolysis, motility, and proliferation of cancer cells were demonstrated by knocking-down ATM in these cells. KU-55933 treatment also inhibits tumor growth and metastasis in vivo in mouse mammary tumors through inhibition of GLUT1 translocation and vimentin expression. These results suggest that ATM acts as a promoter of tumorigenesis in cancer cells with overactivated Akt, and KU-55933 induces apoptosis and inhibits motility by blocking GLUT1-mediated glucose uptake and glycolysis in these cancer cells, which may lead to the use of KU-55933 and its analogs as new preventive or therapeutic agents against cancer.

Synergistic Effect of π-Conjugated [C(NH2)3] Cation and Sb(III) Lone Pair Stereoactivity on Structural Transformation and Second Harmonic Generation.

The search for nonlinear optical (NLO) crystals with excellent comprehensive properties is a formidable challenge. In this work, two guanidine antimony fluorides, C(NH2)3Sb2F7 and C(NH2)3SbF4, were obtained by conjunction of [C(NH2)3] groups with π-conjugated configuration and stereochemically active Sb3+ cations. Due to the different coordination modes of Sb-F bonds and H-F hydrogen bonds, the crystal structure of C(NH2)3Sb2F7 is centrosymmetric (CS), while C(NH2)3SbF4 is noncentrosymmetric (NCS). Optical measurements show that the UV cutoff wavelengths of the title compounds were both less than 240 nm. Thermal studies indicate that these crystals are stable up to 250 °C. In addition, the second harmonic generation (SHG) response of C(NH2)3SbF4 is 2 times that of KH2PO4 (KDP) with the phase-matchable capacity. Theoretical calculations reveal that the large SHG effects of C(NH2)3SbF4 were attributed to the synergy between the planar [C(NH2)3] units and the distorted [SbF4] groups. These results demonstrate that the guanidine antimony fluorides will have potential value as UV NLO materials.

Organic-Inorganic Hybrid Luminescent Hydrogel Glued by a Cationic Polymeric Binder.

Luminescent hydrogels have shown great potential in many fields, such as lighting, display, imaging, and sensing, because of their unique optical properties, biocompatibility, and easy processing. Organic-inorganic hybrid self-assembly can not only enhance the hydrogels' mechanical strength, but also retain their self-healing ability. Herein, a luminescent supramolecular hydrogel is reported, which is formed via self-assembly of the negatively charged Laponite nanosheets and cationic lanthanide coordination polymer. The corresponding results reveal that the multiple binding interaction between Laponite and the polymeric binder is vital for improving the mechanical performance of the obtained luminescent supramolecular hydrogel.

Long noncoding RNA lncBRM promotes proliferation and invasion of colorectal cancer by sponging miR-204-3p and upregulating TPT1.

Long noncoding RNAs (lncRNAs) are characterized as a type of noncoding RNAs over 200 nucleotides with little or none protein-coding potential. In the past years, lncRNAs have been proved to participant in many physiological and pathological processes. However, the role of lncRNAs in colorectal cancer (CRC) still needs more attentions. In our study, we found that lncBRM was highly expressed in CRC samples and the expression level of lncBRM was correlated with metastasis and advanced stage in CRC patients. And also, we showed that high expression of lncBRM predicted poor prognosis. Furthermore, we found that knockdown of lncBRM impaired the proliferation, migration and invasion of CRC cells while overexpressing of lncBRM promotes the proliferation, migration and invasion of CRC cells. Mechanically, we found that lncBRM served as a sponge of miR-204-3p that targeted TPT1. Highly expressed TPT1 can promote the proliferation, migration and invasion of CRC cells. In conclusion, we found that lncBRM was highly expressed in CRC and sponged miR-204-3p to modulate the expression of TPT1.

GPER stabilizes F-actin cytoskeleton and activates TAZ via PLCß-PKC and Rho/ROCK-LIMK-Cofilin pathway.

Actin is a highly abundant cytoskeletal protein that is essential for all eukaryotic cells and participates in many structural and functional roles. It has long been noted that estrogen affects cellular morphology. However, recent studies observed that both estrogen and tamoxifen induce a remarkable cytoskeletal remodeling independent of ER. In addition to ER, G protein-coupled estrogen receptor 1 (GPER, also known as GPR30) also binds to estrogen with high affinity and mediates intracellular estrogenic signaling. Here, we show that activation of GPER by its specific agonist G-1 induces re-organization of F-actin cytoskeleton. We further demonstrate that GPER acts through PLCß-PKC and Rho/ROCK-LIMK-Cofilin pathway, which are upstream regulators of F-actin cytoskeleton assembly, thereby enhancing TAZ nuclear localization and activation. Furthermore, we find that LIMK1/2 is critical for GPER activation-induced breast cancer cell migration. Together, our results suggest that GPER mediates G-1-induced cytoskeleton assembly and GPER promotes breast cancer cell migration via PLCß-PKC and Rho/ROCK-LIMK-Cofilin pathway.

Synergistic Antitumor Effect of Sorafenib in Combination with ATM Inhibitor in Hepatocellular Carcinoma Cells.

Background: Currently, sorafenib is the only systemic chemotherapy drug for advanced stage Hepatocellular carcinoma (HCC). However, emerging data from some clinical HCC patients indicate that sorafenib alone has only moderate antitumor efficacy, and could not inhibit disease metastasis and progression. KU-55933 is a specific ATM inhibitor, which has pro-apoptotic effect on tumor cells. In this study, we analyzed the synergistic effect of sorafenib and KU-55933 on the proliferation of HCC cell lines. Methods: Three HCC cell lines were treated with sorafenib and KU-55933 alone or combination in vitro to investigate inhibitory effect by MTT and wound healing assay. Epithelial to mesenchymal transition (EMT) phenotype change was investigated after sorafenib and KU-55933 treatment by microscopy. Akt signaling pathway proteins including p-Akt, p-mTOR and p-p70S6K were examined by western blot. In addition, cleaved PARP and autophage-related proteins LC3A/B were detected by western blot. Results: KU-55933 can enhance the effect of sorafenib in inhibiting cell proliferation and migration, overcoming EMT, inducing cell apoptosis via inactivating Akt signaling pathway and inducing autophage. The combination treatment with sorafenib and KU-55933 resulted in a strong synergistic effect in vitro. Conclusion: Our results demonstrate that sorafenib combined with KU-55933 treatment does effectively inhibit proliferation of HCC cell lines synergistically. These data suggests that KU-55933 may be a promising chemosensitizer to sorafenib in the treatment of HCC.

Targeting IRES-Mediated p53 Synthesis for Cancer Diagnosis and Therapeutics.

While translational regulation of p53 by the internal ribosome entry site (IRES) at its 5'-untranslated region following DNA damage has been widely accepted, the detailed mechanism underlying the translational control of p53 by its IRES sequence is still poorly understood. In this review, we will focus on the latest progress in identifying novel regulatory proteins of the p53 IRES and in uncovering the functional connection between defective IRES-mediated p53 translation and tumorigenesis. We will also discuss how these findings may lead to a better understanding of the process of oncogenesis and open up new avenues for cancer diagnosis and therapeutics.

Rational Combination of π-Conjugated and Non-π-Conjugated Groups Achieving Strong Nonlinear Optical Response, Large Optical Anisotropy, and UV Light-Switchable Fluorescence.

Combining π-conjugated and non-π-conjugated groups is an important strategy for synthesizing new nonlinear optical (NLO) crystals. However, the second harmonic generation (SHG) response and optical anisotropy can be limited by improper spatial alignment of these functional groups in the crystal structure. In this work, it is revealed that non-π-conjugated [NH2SO3] group acts as both hydrogen bond donor and acceptor, effectively regulating the 2D planar structure formed by π-conjugated [C4N3H6] groups. The resulting organic-inorganic hybrid crystal C4N3H6SO3NH2 exhibits a strong SHG response (2.5 × KDP), large optical anisotropy (0.233@546 nm), and blue-violet and green fluorescence near 360 and 520 nm, respectively. This work expands the methodology for creating new NLO crystals through organic-inorganic hybridization, while also showcasing the potential of C4N3H6SO3NH2 as a multifunctional optical material.

A novel CD8+ T cell-related gene signature as a prognostic biomarker in hepatocellular carcinoma.

CD8+ T cells have great roles in tumor suppression and elimination of various tumors including hepatocellular carcinoma (HCC). Nonetheless, potential prognostic roles of CD8+ T cell-related genes (CD8Gs) in HCC remains unknown. In our study, 416 CD8Gs were identified in HCC, which were enriched in inflammatory and immune signaling pathways. Using The Cancer Genome Atlas dataset, a 5-CD8Gs risk model (KLRB1, FYN, IL2RG, FCER1G, and DGKZ) was constructed, which was verified in International Cancer Genome Consortium and gene expression omnibus datasets. Furthermore, we found that overall survival was independently correlated with the CD8Gs signature, and it was associated with immune- and cancer-related signaling pathways and immune cells infiltration. Finally, drug sensitivity data indicated that 10 chemotherapeutic drugs held promise as therapeutics for HCC patients with high-risk. In conclusion, multi-databases analysis showed that 5-CD8Gs and their signature could be an indicator to predict candidate drugs for HCC therapy.

Establishing and clinically validating a machine learning model for predicting unplanned reoperation risk in colorectal cancer.

BACKGROUND: Colorectal cancer significantly impacts global health, with unplanned reoperations post-surgery being key determinants of patient outcomes. Existing predictive models for these reoperations lack precision in integrating complex clinical data. AIM: To develop and validate a machine learning model for predicting unplanned reoperation risk in colorectal cancer patients. METHODS: Data of patients treated for colorectal cancer (n = 2044) at the First Affiliated Hospital of Wenzhou Medical University and Wenzhou Central Hospital from March 2020 to March 2022 were retrospectively collected. Patients were divided into an experimental group (n = 60) and a control group (n = 1984) according to unplanned reoperation occurrence. Patients were also divided into a training group and a validation group (7:3 ratio). We used three different machine learning methods to screen characteristic variables. A nomogram was created based on multifactor logistic regression, and the model performance was assessed using receiver operating characteristic curve, calibration curve, Hosmer-Lemeshow test, and decision curve analysis. The risk scores of the two groups were calculated and compared to validate the model. RESULTS: More patients in the experimental group were ≥ 60 years old, male, and had a history of hypertension, laparotomy, and hypoproteinemia, compared to the control group. Multiple logistic regression analysis confirmed the following as independent risk factors for unplanned reoperation (P < 0.05): Prognostic Nutritional Index value, history of laparotomy, hypertension, or stroke, hypoproteinemia, age, tumor-node-metastasis staging, surgical time, gender, and American Society of Anesthesiologists classification. Receiver operating characteristic curve analysis showed that the model had good discrimination and clinical utility. CONCLUSION: This study used a machine learning approach to build a model that accurately predicts the risk of postoperative unplanned reoperation in patients with colorectal cancer, which can improve treatment decisions and prognosis.

Ternary Eu3+ crystalline complexes with photoluminescence and triboluminescence for dynamic stress visualization.

Investigation of photoluminescence (PL) and fracture-induced triboluminescence (TL) is necessary for the development of both fundamental theories and practical applications in mechanical energy conversion; however, most known PL/TL-emitting materials are confined to inorganic systems. In this study, a novel lanthanide-based crystalline complex (LnCC), Eu(DBM)3DETA was synthesized via the synergistic coordination of Eu3+ with DBM (Dibenzoylmethane) and DETA (Diethylenetriamine) units, leading to the formation of brighter LnCC with bright red emission, high PL quantum yields (57.19 %) and unique TL characteristics. The key to success in obtaining Eu(DBM)3DETA is the utilization of DETA molecule as synergistic ligand, presenting block crystals with higher coordination number of Eu3+ ions via recrystallization. Due to the dense accumulation of cross-linked three-dimensional frameworks through van der Waals interactions, the fracture-induced piezoelectric effect results in charge separation and excitation through the resultant electric field and discharge, triggering a fast TL response of Eu(DBM)3DETA and expanding the possibilities of the quantitative stress sensing. Importantly, amorphous powders can still recover to their original PL and TL emission intensities after recrystallization in cyclic crystal-to-amorphous phase transitions. The unique PL and TL characteristics of Eu(DBM)3DETA provide promising opportunities to display stress visualization differences of electronic signatures under different forces.

Chloroquine stimulates glucose uptake and glycogen synthase in muscle cells through activation of Akt.

Chloroquine is a pharmaceutical agent that has been widely used to treat patients with malaria. Chloroquine has also been reported to have hypoglycemic effects on humans and animal models of diabetes. Despite many previous studies, the mechanism responsible for its hypoglycemic effect is still unclear. Chloroquine was recently reported to be an activator of ATM, the protein deficient in the Ataxia-telagiectasia (A-T) disease. Since ATM is also known as an insulin responsive protein that mediates Akt activation, we tested the effect of chloroquine on the activity of Akt and its downstream targets. In L6 muscle cells treated with insulin and chloroquine, the phosphorylation of Akt and glucose uptake were dramatically increased compared to cells treated with insulin alone, suggesting that chloroquine is a potent activator of Akt and glucose uptake in these cells. We also found that the reduction of insulin-mediated Akt activity in muscle tissues of insulin resistant rats was partially reversed by chloroquine treatment. Moreover, insulin-mediated phosphorylation of glycogen synthase kinase-3ß in L6 cells was greatly enhanced by chloroquine. A substantial decrease in phosphorylation of glycogen synthase was also observed in chloroquine-treated L6 cells, indicating enhanced activity of glycogen synthase. Taken together, our results not only show that chloroquine is a novel activator of Akt that stimulates glucose uptake and glycogen synthase, but also validate chloroquine as a potential therapeutic agent for patients with type 2 diabetes mellitus.

Influence of the physical terrestrial Arctic in the eco-climate system.

This synthesis paper provides a summary of the major components of the physical terrestrial Arctic and the influences of their changes upon the larger eco-climate system. Foci here are snow cover, permafrost, and land hydrology. During the last century, snow cover duration has shortened in a large portion of the circum-Arctic, mainly because of its early northward retreat in spring due to warming. Winter precipitation has generally increased, resulting in an increase in maximum snow depth over large areas. This is consistent with the increase in river discharge over large Russian watersheds. Soil temperature has also increased, and the active layer has deepened in most of the permafrost regions, whereas thinning of the seasonally frozen layer has been observed in areas not underlain by permafrost. These active components are mutually interrelated, conditioned by ambient micro- to landscape-level topography and local surface and subsurface conditions, and they are closely related with vegetation and ecology, as evidenced by evolution in the late Quaternary. Further, we provide examples and arguments for discussions on the pathways through which changes in the Arctic terrestrial system can affect or propagate to remote areas beyond the Arctic, reaching to the extratropics in the larger climate system. These considerations include dynamical and thermodynamical responses and feedbacks,'modification of hemisphere-scale atmospheric circulation associated with troposphere-stratosphere couplings, and moisture intrusion at a continental scale.

Identifying novel disease categories through divergence optimization: An approach to prevent misdiagnosis in medical imaging.

Given the significant changes in human lifestyle, the incidence of colon cancer has rapidly increased. The diagnostic process can often be complicated due to symptom similarities between colon cancer and other colon-related diseases. In an effort to minimize misdiagnosis, deep learning-based approaches for colon cancer diagnosis have notably progressed within the field of clinical medicine, offering more precise detection and improved patient outcomes. Despite these advancements, practical application of these techniques continues to encounter two major challenges: 1) due to the need for expert annotation, only a limited number of labels are utilized for diagnosis; and 2) the existence of diverse disease types can lead to misdiagnosis when the model encounters unfamiliar disease categories. To overcome these hurdles, we present a method incorporating Universal Domain Adaptation (UniDA). By optimizing the divergence of samples in the source domain, our method detects noise. Furthermore, to identify categories that are not present in the source domain, we optimize the divergence of unlabeled samples in the target domain. Experimental validation on two gastrointestinal datasets demonstrates that our method surpasses current state-of-the-art domain adaptation techniques in identifying unknown disease classes. It is worth noting that our proposed method is the first work of medical image diagnosis aimed at the identification of unknown categories of diseases.

Self-strengthen luminescent hydrogel.

For typical synthetic materials, continue mechanical loading usually cause damage and even failure, because they are closed systems, without substance exchange with surroundings and structural reconstruction after damage. Double-network (DN) hydrogels have recently been demonstrated to generate radicals under mechanical loading. In this work, DN hydrogel provided with sustained monomer and lanthanide complex supply undergo self-growth, and thus simultaneous self-strengthen in both mechanical performance and luminescence intensity are realized through bond rupture-initiated mechanoradical polymerization. This strategy proves the feasibility of imparting desired functions to the DN hydrogel by mechanical stamping, and provides a new strategy for the design of luminescent soft materials with high fatigue resistance.

Characterization of Lipid Alterations by Oncogenic PIK3CA Mutations Using Untargeted Lipidomics in Breast Cancer.

Lipids play crucial biological roles in health and disease, including in cancers. The phosphatidylinositol 3-kinase (PI3K) signaling pathway is a pivotal promoter of cell growth and proliferation in various types of cancer. The somatic mutations in PIK3CA, the gene coding for the catalytic subunit p110α of PI3K, are frequently present in cancer cells, including breast cancer. Although the most prominent mutants, represented by single amino acid substitutions in the helical domain in exon 9 (E545K) and the kinase domain in exon 20 (H1047R) are known to cause a gain of PI3K function, activate AKT signaling and induce oncogenic transformation, the effect of these mutations on cellular lipid profiles has not been studied. We carried out untargeted lipidomics using liquid chromatography-tandem mass spectrometry to detect the lipid alterations in mammary gland epithelial MCF10A cells with isogenic knockin of these mutations. A total of 536 species of lipids were analyzed. We found that the levels of monosialogangliosides, signaling molecules known to enhance cell motility through PI3K/AKT pathway, were significantly higher in both mutants. In addition, triglycerides and ceramides, lipid molecules known to be involved in promoting lipid droplet production, cancer cell migration and invasion, were increased, whereas lysophosphatidylcholines and phosphatidylcholines that are known to inhibit cancer cell motility were decreased in both mutants. Our results provide novel insights into a potential link between altered lipid profile and carcinogenesis caused by the PIK3CA hotspot mutations. In addition, we suggest untargeted lipidomics offers prospects for precision/personalized medicine by unpacking new molecular substrates of cancer biology.