Generation and Application of Mouse-Rat Allodiploid Embryonic Stem Cells.

Mammalian interspecific hybrids provide unique advantages for mechanistic studies of speciation, gene expression regulation, and X chromosome inactivation (XCI) but are constrained by their limited natural resources. Previous artificially generated mammalian interspecific hybrid cells are usually tetraploids with unstable genomes and limited developmental abilities. Here, we report the generation of mouse-rat allodiploid embryonic stem cells (AdESCs) by fusing haploid ESCs of the two species. The AdESCs have a stable allodiploid genome and are capable of differentiating into all three germ layers and early-stage germ cells. Both the mouse and rat alleles have comparable contributions to the expression of most genes. We have proven AdESCs as a powerful tool to study the mechanisms regulating X chromosome inactivation and to identify X inactivation-escaping genes, as well as to efficiently identify genes regulating phenotypic differences between species. A similar method could be used to create hybrid AdESCs of other distantly related species.

A pharynx-to-brain axis controls pharyngeal inflammation-induced anxiety.

Anxiety is a remarkably common condition among patients with pharyngitis, but the relationship between these disorders has received little research attention, and the underlying neural mechanisms remain unknown. Here, we show that the densely innervated pharynx transmits signals induced by pharyngeal inflammation to glossopharyngeal and vagal sensory neurons of the nodose/jugular/petrosal (NJP) superganglia in mice. Specifically, the NJP superganglia project to norepinephrinergic neurons in the nucleus of the solitary tract (NTSNE). These NTSNE neurons project to the ventral bed nucleus of the stria terminalis (vBNST) that induces anxiety-like behaviors in a murine model of pharyngeal inflammation. Inhibiting this pharynx→NJP→NTSNE→vBNST circuit can alleviate anxiety-like behaviors associated with pharyngeal inflammation. This study thus defines a pharynx-to-brain axis that mechanistically links pharyngeal inflammation and emotional response.

Hepatocyte-specific Selenoi deficiency predisposes mice to hepatic steatosis and obesity.

Selenoprotein I (Selenoi) is highly expressed in liver and plays a key role in lipid metabolism as a phosphatidylethanolamine (PE) synthase. However, the precise function of Selenoi in the liver remains elusive. In the study, we generated hepatocyte-specific Selenoi conditional knockout (cKO) mice on a high-fat diet to identify the physiological function of Selenoi. The cKO group exhibited a significant increase in body weight, with a 15.6% and 13.7% increase in fat accumulation in white adipose tissue (WAT) and the liver, respectively. Downregulation of the lipolysis-related protein (p-Hsl) and upregulation of the adipogenesis-related protein (Fasn) were observed in the liver of cKO mice. The cKO group also showed decreased oxygen consumption (VO2), carbon dioxide production (VCO2), and energy expenditure (p < .05). Moreover, various metabolites of the steroid hormone synthesis pathway were affected in the liver of cKO mice. A potential cascade of Selenoi-phosphatidylethanolamine-steroid hormone synthesis might serve as a core mechanism that links hepatocyte-specific Selenoi cKO to biochemical and molecular reactions. In conclusion, we revealed that Selenoi inhibits body fat accumulation and hepatic steatosis and elevates energy consumption; this protein could also be considered a therapeutic target for such related diseases.

Keratose hydrogel for tissue regeneration and drug delivery.

Keratin (KRT), a natural fibrous structural protein, can be classified into two categories: "soft" cytosolic KRT that is primarily found in the epithelia tissues (e.g., skin, the inner lining of digestive tract) and "hard" KRT that is mainly found in the protective tissues (e.g., hair, horn). The latter is the predominant form of KRT widely used in biomedical research. The oxidized form of extracted KRT is exclusively denoted as keratose (KOS) while the reduced form of KRT is termed as kerateine (KRTN). KOS can be processed into various forms (e.g., hydrogel, films, fibers, and coatings) for different biomedical applications. KRT/KOS offers numerous advantages over other types of biomaterials, such as bioactivity, biocompatibility, degradability, immune/inflammatory privileges, mechanical resilience, chemical manipulability, and easy accessibility. As a result, KRT/KOS has attracted considerable attention and led to a large number of publications associated with this biomaterial over the past few decades; however, most (if not all) of the published review articles focus on KRT regarding its molecular structure, biochemical/biophysical properties, bioactivity, biocompatibility, drug/cell delivery, and in vivo transplantation, as well as its applications in biotechnical products and medical devices. Current progress that is directly associated with KOS applications in tissue regeneration and drug delivery appears an important topic that merits a commentary. To this end, the present review aims to summarize the current progress of KOS-associated biomedical applications, especially focusing on the in vitro and in vivo effects of KOS hydrogel on cultured cells and tissue regeneration following skin injury, skeletal muscle loss, peripheral nerve injury, and cardiac infarction.

Organic-Inorganic Rare-Earth Double Perovskite Ferroelectric with Large Piezoelectric Response and Ferroelasticity for Flexible Composite Energy Harvesters.

Hybrid organic-inorganic perovskite (HOIP) ferroelectric materials have great potential for developing self-powered electronic transducers owing to their impressive piezoelectric performance, structural tunability and low processing temperatures. Nevertheless, their inherent brittle and low elastic moduli limit their application in electromechanical conversion. Integration of HOIP ferroelectrics and soft polymers is a promising solution. In this work, a hybrid organic-inorganic rare-earth double perovskite ferroelectric, [RM3HQ]2RbPr(NO3)6 (RM3HQ = (R)-N-methyl-3-hydroxylquinuclidinium) is presented, which possesses multiaxial nature, ferroelasticity and satisfactory piezoelectric properties, including piezoelectric charge coefficient (d33) of 102.3 pC N-1 and piezoelectric voltage coefficient (g33) of 680 × 10-3 V m N-1. The piezoelectric generators (PEG) based on composite films of [RM3HQ]2RbPr(NO3)6@polyurethane (PU) can generate an open-circuit voltage (Voc) of 30 V and short-circuit current (Isc) of 18 µA, representing one of the state-of-the-art PEGs to date. This work has promoted the exploration of new HOIP ferroelectrics and their development of applications in electromechanical conversion devices.

Prognostic and predictive value of super-enhancer-derived signatures for survival and lung metastasis in osteosarcoma.

BACKGROUND: Risk stratification and personalized care are crucial in managing osteosarcoma due to its complexity and heterogeneity. However, current prognostic prediction using clinical variables has limited accuracy. Thus, this study aimed to explore potential molecular biomarkers to improve prognostic assessment. METHODS: High-throughput inhibitor screening of 150 compounds with broad targeting properties was performed and indicated a direction towards super-enhancers (SEs). Bulk RNA-seq, scRNA-seq, and immunohistochemistry (IHC) were used to investigate SE-associated gene expression profiles in osteosarcoma cells and patient tissue specimens. Data of 212 osteosarcoma patients who received standard treatment were collected and randomized into training and validation groups for retrospective analysis. Prognostic signatures and nomograms for overall survival (OS) and lung metastasis-free survival (LMFS) were developed using Cox regression analyses. The discriminatory power, calibration, and clinical value of nomograms were evaluated. RESULTS: High-throughput inhibitor screening showed that SEs significantly contribute to the oncogenic transcriptional output in osteosarcoma. Based on this finding, focus was given to 10 SE-associated genes with distinct characteristics and potential oncogenic function. With multi-omics approaches, the hyperexpression of these genes was observed in tumor cell subclusters of patient specimens, which were consistently correlated with poor outcomes and rapid metastasis, and the majority of these identified SE-associated genes were confirmed as independent risk factors for poor outcomes. Two molecular signatures were then developed to predict survival and occurrence of lung metastasis: the SE-derived OS-signature (comprising LACTB, CEP55, SRSF3, TCF7L2, and FOXP1) and the SE-derived LMFS-signature (comprising SRSF3, TCF7L2, FOXP1, and APOLD1). Both signatures significantly improved prognostic accuracy beyond conventional clinical factors. CONCLUSIONS: Oncogenic transcription driven by SEs exhibit strong associations with osteosarcoma outcomes. The SE-derived signatures developed in this study hold promise as prognostic biomarkers for predicting OS and LMFS in patients undergoing standard treatments. Integrative prognostic models that combine conventional clinical factors with these SE-derived signatures demonstrate substantially improved accuracy, and have the potential to facilitate patient counseling and individualized management.

Genistein alleviates dextran sulfate sodium-induced colitis in mice through modulation of intestinal microbiota and macrophage polarization.

OBJECTIVES: Ulcerative colitis (UC) is a colonic immune system disorder, manifested with long duration and easy relapse. Genistein has been reported to possess various biological activities. However, it remains unclear whether genistein can ameliorate UC by modulating the homeostasis of the intestinal bacterial community. METHODS: The dextran sodium sulfate (DSS)-induced UC mice were administrated with genistein (20 mg/kg/day) or genistein (40 mg/kg/day) for ten days. The general physical condition of the mice was monitored. After sacrifice, the changes in colon length and colonic pathological morphology were observed. The expression of intestinal barrier proteins, inflammatory cytokines, and macrophage markers in the colon was detected. The composition and metabolic products of the intestinal microbiota were analyzed. RESULTS: Genistein treatment visibly improved body weight change and disease activity index in DSS-induced mice. Genistein treatment ameliorated colonic pathological alterations and promoted the expression of mucin-2 and tight junction proteins. Genistein administration inhibited myeloperoxidase activity and colonic inflammatory cytokines. Furthermore, genistein administration improved the structure of the intestinal microbial community, promoted the production of short-chain fatty acids, and modulated macrophage polarization. CONCLUSIONS: These results revealed that genistein mediated macrophage polarization balance by improving intestinal microbiota and its metabolites, thereby alleviating DSS-induced colitis.

Anticancer efficacy triggered by synergistically modulating the homeostasis of anions and iron: Design, synthesis and biological evaluation of dual-functional squaramide-hydroxamic acid conjugates.

Targeting the homeostasis of anions and iron has emerged as a promising therapeutic approach for the treatment of cancers. However, single-targeted agents often fall short of achieving optimal treatment efficacy. Herein we designed and synthesized a series of novel dual-functional squaramide-hydroxamic acid conjugates that are capable of synergistically modulating the homeostasis of anions and iron. Among them, compound 16 exhibited the most potent antiproliferative activity against a panel of selected cancer cell lines, and strong in vivo anti-tumor efficacy. This compound effectively elevated lysosomal pH through anion transport, and reduced the levels of intracellular iron. Compound 16 could disturb autophagy in A549 cells and trigger robust apoptosis. This compound caused cell cycle arrest at the G1/S phase, altered the mitochondrial function and elevated ROS levels. The present findings clearly demonstrated that synergistic modulation of anion and iron homeostasis has high potentials in the development of promising chemotherapeutic agents with dual action against cancers.

Inhibiting ferroptosis in brain microvascular endothelial cells: A potential strategy to mitigate polystyrene nanoplastics‒induced blood‒brain barrier dysfunction.

Polystyrene nanoplastics (PS-NPs), a group of ubiquitous pollutants, may injure the central nervous system through the blood‒brain barrier (BBB). However, whether exposure to PS-NPs contributes to BBB disruption and the underlying mechanisms are still unclear. In vivo, we found that PS-NPs (25 mg/kg BW) could significantly increase BBB permeability in mice and downregulate the distribution of the tight junction-associated protein zona occludens 1 (ZO-1) in brain microvascular endothelial cells (BMECs). Using an in vitro BBB model, exposure to PS-NPs significantly reduced the transendothelial electrical resistance and altered ZO-1 expression and distribution in a dose-dependent manner. RNA-seq analysis and functional investigations were used to investigate the molecular pathways involved in the response to PS-NPs. The results revealed that the ferroptosis and glutathione metabolism signaling pathways were related to the disruption of the BBB model caused by the PS-NPs. PS-NPs treatment promoted ferroptosis in bEnd.3 cells by inducing disordered glutathione metabolism in addition to Fe2+ and lipid peroxide accumulation, while suppressing ferroptosis with ferrostatin-1 (Fer-1) suppressed ferroptosis-related changes in bEnd.3 cells subjected to PS-NPs. Importantly, Fer-1 alleviated the decrease in ZO-1 expression in bEnd.3 cells and the exacerbation of BBB damage induced by PS-NPs. Collectively, our findings suggest that inhibiting ferroptosis in BMECs may serve as a potential therapeutic target against BBB disruption induced by PS-NPs exposure.

Synovium microenvironment-responsive injectable hydrogel inducing modulation of macrophages and elimination of synovial fibroblasts for enhanced treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a progressive autoimmune disease accompanied by joint swelling, cartilage erosion and bone damage. Drug therapy for RA has been restricted due to poor therapeutic effect, recurrence and adverse effects. Macrophages and synovial fibroblasts both play important roles in the pathology of RA. Macrophages secrete large amount of pro-inflammatory cytokines, while synovial fibroblasts are tightly correlated with hypoxia synovium microenvironment, cytokine release, recruitment of pro-inflammatory cells, bone and cartilage erosion. Therefore, in this timely research, an injectable and pH-sensitive peptide hydrogel loading methotrexate (MTX) and bismuthene nanosheet/polyethyleneimine (BiNS/PEI) has been developed to reduce the activity of macrophages and eliminate over-proliferated synovial fibroblasts simultaneously. MTX can reduce the cytokine secretion of macrophages/anti-apoptosis property of synovial fibroblasts and BiNS/PEI can eliminate synovial fibroblasts via photodynamic therapy (PDT) and photothermal therapy (PTT) routes. The hydrogel was injected into the acidic inflammatory synovium for precise targeting and served as a drug reservoir for pH responsive and sustained drug release, while improving the bioavailability and reducing the toxicity of MTX. Excellent therapeutic efficacy has been achieved in both in vivo and in vitro studies, and this unique drug delivery system provides a new and robust strategy to eliminate synovial fibroblasts and modulate immune system for RA treatment in clinical.

A single center retrospective study: Comparison between centrifugal separation plasma exchange with ACD-A and membrane separation plasma exchange with heparin on acute liver failure and acute on chronic liver failure.

The purpose of this retrospective study is to compare the efficacy and safety of the centrifugal separation therapeutic plasma exchange (TPE) using citrate anticoagulant (cTPEc) with membrane separation TPE using heparin anticoagulant (mTPEh) in liver failure patients. The patients treated by cTPEc were defined as cTPEc group and those treated by mTPEh were defined as mTPEh group, respectively. Clinical characteristics were compared between the two groups. Survival analyses of two groups and subgroups classified by the model for end-stage liver disease (MELD) score were performed by Kaplan-Meier method and were compared by the log-rank test. In this study, there were 51 patients in cTPEc group and 18 patients in mTPEh group, respectively. The overall 28-day survival rate was 76% (39/51) in cTPEc group and 61% (11/18) in mTPEh group (P > .05). The 90-day survival rate was 69% (35/51) in cTPEc group and 50% (9/18) in mTPEh group (P > .05). MELD score = 30 was the best cut-off value to predict the prognosis of patients with liver failure treated with TPE, in mTPEh group as well as cTPEc group. The median of total calcium/ionized calcium ratio (2.84, range from 2.20 to 3.71) after cTPEc was significantly higher than the ratio (1.97, range from 1.73 to 3.19) before cTPEc (P < .001). However, there was no significant difference between the mean concentrations of total calcium before cTPEc and at 48 h after cTPEc. Our study concludes that there was no statistically significant difference in survival rate and complications between cTPEc and mTPEh groups. The liver failure patients tolerated cTPEc treatment via peripheral vascular access with the prognosis similar to mTPEh. The prognosis in patients with MELD score < 30 was better than in patients with MELD score ≥ 30 in both groups. In this study, the patients with acute liver failure (ALF) and acute on chronic liver failure (ACLF) treated with cTPEc tolerated the TPE frequency of every other day without significant clinical adverse event of hypocalcemia with similar outcomes to the mTPEh treatment. For liver failure patients treated with cTPEc, close clinical observation and monitoring ionized calcium are necessary to ensure the patients' safety.

Simvastatin attenuates silica-induced pulmonary inflammation and fibrosis in rats via the AMPK-NOX pathway.

BACKGROUND: Simvastatin (Sim), a hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has been widely used in prevention and treatment of cardiovascular diseases. Studies have suggested that Sim exerts anti-fibrotic effects by interfering fibroblast proliferation and collagen synthesis. This study was to determine whether Sim could alleviate silica-induced pulmonary fibrosis and explore the underlying mechanisms. METHODS: The rat model of silicosis was established by the tracheal perfusion method and treated with Sim (5 or 10 mg/kg), AICAR (an AMPK agonist), and apocynin (a NOX inhibitor) for 28 days. Lung tissues were collected for further analyses including pathological histology, inflammatory response, oxidative stress, epithelial mesenchymal transformation (EMT), and the AMPK-NOX pathway. RESULTS: Sim significantly reduced silica-induced pulmonary inflammation and fibrosis at 28 days after administration. Sim could reduce the levels of interleukin (IL)-1ß, IL-6, tumor necrosis factor-α and transforming growth factor-ß1 in lung tissues. The expressions of hydroxyproline, α-SMA and vimentin were down-regulated, while E-cad was increased in Sim-treated rats. In addition, NOX4, p22pox, p40phox, p-p47phox/p47phox expressions and ROS levels were all increased, whereas p-AMPK/AMPK was decreased in silica-induced rats. Sim or AICAR treatment could notably reverse the decrease of AMPK activity and increase of NOX activity induced by silica. Apocynin treatment exhibited similar protective effects to Sim, including down-regulating of oxidative stress and inhibition of the EMT process and inflammatory reactions. CONCLUSIONS: Sim attenuates silica-induced pulmonary inflammation and fibrosis by downregulating EMT and oxidative stress through the AMPK-NOX pathway.

Relationships between bilateral auditory brainstem activity and inter-implant interval in children with cochlear implants.

PURPOSE: To investigate the effect of the interval between bilateral cochlear implantation on the development of bilateral peripheral auditory pathways as revealed by the electrically evoked auditory brainstem response (EABR). METHODS: Fifty-eight children with profound bilateral sensorineural hearing loss were recruited. Among them, 33 children received sequential bilateral cochlear implants (CIs), and 25 children received simultaneous bilateral CIs. The bilateral EABRs evoked by electrical stimulation from the CI electrode were recorded on the day of second-side CI activation. RESULTS: The latencies of wave III (eIII) and wave V (eV) were significantly shorter on the first CI side than on the second CI side in children with sequential bilateral CIs but were similar between the two sides in children with simultaneous bilateral CIs. Furthermore, the latencies were prolonged from apical to basal channels along the cochlea in the two groups. In children with sequential CIs, the inter-implant interval was negatively correlated with the eV latency on the first CI side and was positively correlated with bilateral differences in the eIII and eV latencies. CONCLUSIONS: Unilateral CI use promotes the maturation of ipsilateral auditory conduction function. However, a longer inter-implant interval results in more unbalanced development of bilateral auditory brainstem pathways. Bilateral cochlear implantation with no or a short interval is recommended.

Unusual Thermal Quenching of Photoluminescence from an Organic-Inorganic Hybrid [MnBr4 ]2- -based Halide Mediated by Crystalline-Crystalline Phase Transition.

The ability to generate and manipulate photoluminescence (PL) behavior has been of primary importance for applications in information security. Excavating novel optical effects to create more possibilities for information encoding has become a continuous challenge. Herein, we present an unprecedented PL temporary quenching that highly couples with thermodynamic phase transition in a hybrid crystal (DMML)2 MnBr4 (DMML=N,N-dimethylmorpholinium). Such unusual PL behavior originates from the anomalous variation of [MnBr4 ]2- tetrahedrons that leads to non-radiation recombination near the phase transition temperature of 340 K. Remarkably, the suitable detectable temperature, narrow response window, high sensitivity, and good cyclability of this PL temporary quenching will endow encryption applications with high concealment, operational flexibility, durability, and commercial popularization. Profited from these attributes, a fire-new optical encryption model is devised to demonstrate high confidential information security. This unprecedented optical effect would provide new insights and paradigms for the development of luminescent materials to enlighten future information encryption.

Organic-Inorganic Hybrid Ferroelectric and Antiferroelectric with Afterglow Emission.

Luminescent ferroelectrics are holding exciting prospect for integrated photoelectronic devices due to potential light-polarization interactions at electron scale. Integrating ferroelectricity and long-lived afterglow emission in a single material would offer new possibilities for fundamental research and applications, however, related reports have been a blank to date. For the first time, we here achieved the combination of notable ferroelectricity and afterglow emission in an organic-inorganic hybrid material. Remarkably, the presented (4-methylpiperidium)CdCl3 also shows noticeable antiferroelectric behavior. The implementation of cationic customization and halogen engineering not only enables a dramatic enhancement of Curie temperature of 114.4 K but also brings a record longest emission lifetime up to 117.11 ms under ambient conditions, realizing a leapfrog improvement of at least two orders of magnitude compared to reported hybrid ferroelectrics so far. This finding would herald the emergence of novel application potential, such as multi-level density data storage or multifunctional sensors, towards the future integrated optoelectronic devices with multitasking capabilities.

α7 Nicotinic acetylcholine receptor: a key receptor in the cholinergic anti-inflammatory pathway exerting an antidepressant effect.

Depression is a common mental illness, which is related to monoamine neurotransmitters and the dysfunction of the cholinergic, immune, glutamatergic, and neuroendocrine systems. The hypothesis of monoamine neurotransmitters is one of the commonly recognized pathogenic mechanisms of depression; however, the drugs designed based on this hypothesis have not achieved good clinical results. A recent study demonstrated that depression and inflammation were strongly correlated, and the activation of alpha7 nicotinic acetylcholine receptor (α7 nAChR)-mediated cholinergic anti-inflammatory pathway (CAP) in the cholinergic system exhibited good therapeutic effects against depression. Therefore, anti-inflammation might be a potential direction for the treatment of depression. Moreover, it is also necessary to further reveal the key role of inflammation and α7 nAChR in the pathogenesis of depression. This review focused on the correlations between inflammation and depression as well-discussed the crucial role of α7 nAChR in the CAP.

Introducing Ferroelasticity into 1D Hybrid Lead Halide Semiconductor by Halogen Substitution Strategy.

Organic-inorganic hybrid lead halide perovskites (OLHPs), represented by (CH3 NH3 )PbI3 , are one of the research focus due to their exceptional performance in optoelectronic applications, and ferroelastic domain walls are benign to their charge carrier transport that is confirmed recently. Among them, the 1D OLHPs feature better stability against desorption and moisture, but related 1D ones possessing ferroelasticity are rarely investigated and reported so far. In this work, the 1D ferroelastic semiconductor (N-iodomethyl-N-methyl-morpholinium)PbI3 ((IDMML)PbI3 ) is prepared successfully by introducing successively halogenate atoms from Cl, Br to I into the organic cation of the prototype (N,N-dimethylmorpholinium)PbI3 ((DMML)PbI3 ). Notably, (IDMML)PbI3 shows the narrow bandgap energy (≈2.34 eV) according to the ultraviolet-visible absorption spectrum and the theoretical calculation, and possesses the evident photoconductive characteristic with the on/off ratio of current of ≈50 under the 405 nm light irradiation. This work provides a new case for the ferroelastic OLHPs and will inspire intriguing research in the field of optoelectronic.

Inserting Single-Atom Zn by Tannic Acid Confinement To Regulate the Selectivity of Pd Nanocatalysts for Hydrogenation Reactions.

Precisely controlling the selectivity of nanocatalysts has always been a hot topic in heterogeneous catalysis but remains difficult owing to their complex and inhomogeneous catalytic sites. Herein, an effective strategy to regulate the chemoselectivity of Pd nanocatalysts for selective hydrogenation reactions by inserting single-atom Zn into Pd nanoparticles is reported. Taking advantage of the tannic acid coating-confinement strategy, small-sized Pd nanoparticles with inserted single-atom Zn are obtained on the O-doped carbon-coated alumina. Compared with the pure Pd nanocatalyst, the Pd nanocatalyst with single-atom Zn insertion exhibits prominent selectivity for the hydrogenation of p-iodonitrobenzene to afford the hydrodeiodination product instead of nitro hydrogenation ones. Further computational studies reveal that the single-atom Zn on Pd nanoparticles strengthens the adsorption of the nitro group to avoid its reduction and increases the d-band center of Pd atoms to facilitate the reduction of the iodo group, which leads to enhanced selectivity. This work provides new guidelines to tune the selectivity of nanocatalysts with guest single-atom sites.

Clinical characteristics and therapeutic response of differentiated thyroid carcinoma with obesity and diabetes.

BACKGROUND: The effects of obesity and diabetes on the clinical outcomes of differentiated thyroid cancer (DTC) remain unclear. OBJECTIVES: To explore the association between obesity and diabetes with pathological features and therapeutic response of DTC. METHODS: Patients were categorized based on body mass index (BMI) and glycemic status. Compare the correlation between BMI and glycemic status with pathological features and therapeutic response of DTC. To analyze the independent risk factors for the aggressiveness of DTC. RESULTS: The proportion of patients with bilateral tumors was higher in the overweight, obese and diabetes group (P = 0.001, 0.045). The overweight group demonstrated a higher TNM stage (P = 0.004), while the T and TNM stages were higher in the diabetes group (P = 0.032, 0.000). The probability of distant metastasis increases by 37.4% for each unit of BMI increase (odds ratio (OR) = 1.374, CI 95% 1.061-1.778, P < 0.05). The BMI of Biochemical Incomplete Response (BIR) is significantly higher than that of Excellent Response (ER) (P = 0.015), the fasting plasma glucose (FPG) of Structural Incomplete (SIR) was significantly higher than that of ER and BIR (P = 0.030, 0.014). CONCLUSION: Obesity and diabetes have effect on DTC aggressiveness. BMI and FPG have correlation with the therapeutic response of DTC patients.

Bicyclic Amidine-Triggered Cyclization of o-Alkynylisocyanobenzenes: Synthesis of Lactam-Derived Quinolines.

Efficient access to the synthesis of lactam-derived quinoline through a bicyclic amidine-triggered cyclization reaction from readily prepared o-alkynylisocyanobenzenes has been developed. The reaction was initiated by nucleophilic attack of the bicyclic amidines to o-alkynylisocyanobenzenes, subsequently with intramolecular cyclization to produce a DBU-quinoline-based amidinium salt, followed by hydrolysis to afford the lactam-derived quinoline in moderate to good yields.