Unconventional spectral signature of Tc in a pure d-wave superconductor.

In conventional superconductors, the phase transition into a zero-resistance and perfectly diamagnetic state is accompanied by a jump in the specific heat and the opening of a spectral gap1. In the high-transition-temperature (high-Tc) cuprates, although the transport, magnetic and thermodynamic signatures of Tc have been known since the 1980s2, the spectroscopic singularity associated with the transition remains unknown. Here we resolve this long-standing puzzle with a high-precision angle-resolved photoemission spectroscopy (ARPES) study on overdoped (Bi,Pb)2Sr2CaCu2O8+δ (Bi2212). We first probe the momentum-resolved electronic specific heat via spectroscopy and reproduce the specific heat peak at Tc, completing the missing link for a holistic description of superconductivity. Then, by studying the full momentum, energy and temperature evolution of the spectra, we reveal that this thermodynamic anomaly arises from the singular growth of in-gap spectral intensity across Tc. Furthermore, we observe that the temperature evolution of in-gap intensity is highly anisotropic in the momentum space, and the gap itself obeys both the d-wave functional form and particle-hole symmetry. These findings support the scenario that the superconducting transition is driven by phase fluctuations. They also serve as an anchor point for understanding the Fermi arc and pseudogap phenomena in underdoped cuprates.

Primary cilium participates in radiation-induced bystander effects through TGF-ß1 signaling.

Many studies have indicated that tumor growth factor-beta (TGF-ß) signaling mediates radiation-induced bystander effects (RIBEs). The primary cilium (PC) coordinates several signaling pathways including TGF-ß signaling to regulate diverse cellular processes. But whether the PC participates in TGF-ß induced RIBEs remains unclear. The cellular levels of TGF-ß1 were detected by western blot analysis and the secretion of TGF-ß1 was measured by ELISA kit. The ciliogenesis was altered by CytoD treatment, STIL siRNA transfection, IFT88 siRNA transfection, or KIF3a siRNA transfection, separately, and was detected by western blot analysis and immunofluorescence staining. G0 /G1 phase cells were arrested by serum starvation and S phase cells were induced by double thymidine block. The TGF-ß1 signaling was interfered by LY2109761, a TGF-ß receptor 1 (TßR1) inhibitor, or TGF-ß1 neutral antibody. The DNA damages were induced by TGF-ß1 or radiated conditional medium (RCM) from irradiated cells and were reflected by p21 expression, 53BP1 foci, and γH2AX foci. Compared with unirradiated control, both A549 and Beas-2B cells expressed and secreted more TGF-ß1 after carbon ion beam or X-ray irradiation. RCM collected from irradiated cells or TGF-ß1 treatment caused an increase of DNA damage in cocultured unirradiated Beas-2B cells while blockage of TGF-ß signaling by TßR1 inhibitor or TGF-ß1 neutral antibody alleviates this phenomenon. IFT88 siRNA or KIF3a siRNA impaired PC formation resulted in an aggravated DNA damage in bystander cells, while elevated PC formation by CytoD or STIL siRNA resulted in a decrease of DNA damage. Furthermore, TGF-ß1 induced more DNA damages in S phases cells which showed lower PC formation rate and less DNA damages in G0 /G1 phase cells which showed higher PC formation rate. This study demonstrates the particular role of primary cilia during RCM induced DNA damages through TGF-ß1 signaling restriction and thereby provides a functional link between primary cilia and RIBEs.

Application of LAMP coupled with NALF for precise detection of mycoplasma pneumoniae.

Mycoplasma pneumoniae (MP),as the most commonly infected respiratory pathogen in community-acquired pneumonia in preschool children,has becoming a prominent factor affecting children's respiratory health.Currently, there is a lack of easy, rapid, and accurate laboratory testing program for MP infection, which causes comparatively difficulty for clinical diagnostic.Here,we utilize loop-mediated isothermal amplification (LAMP) to amplify and characterize the P1 gene of MP, combined with nucleic acid lateral flow (NALF) for fast and visuallized detection of MP.Furthermore, we evaluated and analyzed the sensitivity, specificity and methodological consistency of the method.The results showed that the limit of detection(LoD) of MP-LAMP-NALF assay was down to 100 copys per reaction and there was no cross-reactivity with other pathogens infected the respiratory system. The concordance rate between MP-LAMP-NALF assay with quantitative real-time PCR was 94.3 %,which exhibiting excellent testing performance.We make superior the turnaround time of the MP-LAMP-NALF assay, which takes only about 50 min. In addition, there is no need for precision instruments and no restriction on the laboratory site.Collectively, LAMP-NALF assay targeting the P1 gene for Mycoplasma pneumoniae detection was a easy, precise and visual test which could be widely applied in outpatient and emergency departments or primary hospitals.When further optimized, it could be used as "point-of-care testing" of pathogens or multiple testing for pathogens.

FL-DTD: an integrated pipeline to predict the drug interacting targets by feedback loop-based network analysis.

Drug target discovery is an essential step to reveal the mechanism of action (MoA) underlying drug therapeutic effects and/or side effects. Most of the approaches are usually labor-intensive while unable to identify the tissue-specific interacting targets, especially the targets with weaker drug binding affinity. In this work, we proposed an integrated pipeline, FL-DTD, to predict the drug interacting targets of novel compounds in a tissue-specific manner. This method was built based on a hypothesis that cells under a status of homeostasis would take responses to drug perturbation by activating feedback loops. Therefore, the drug interacting targets can be predicted by analyzing the network responses after drug perturbation. We evaluated this method using the expression data of estrogen stimulation, gene manipulation and drug perturbation and validated its good performance to identify the annotated drug targets. Using STAT3 as a target protein, we applied this method to drug perturbation data of 500 natural compounds and predicted five compounds with STAT3 interacting activities. Experimental assay validated the STAT3-interacting activities of four compounds. Overall, our evaluation suggests that FL-DTD predicts the drug interacting targets with good accuracy and can be used for drug target discovery.

Evaluation of models to predict prognosis in patients with advanced hepatocellular carcinoma treated with TACE combined with apatinib.

BACKGROUND: The HAP, Six-and-Twelve, Up to Seven, and ALBI scores have been substantiated as reliable prognostic markers in patients presenting with intermediate and advanced hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) treatment. Given this premise, our research aims to assess the predictive efficacy of these models in patients with intermediate and advanced HCC receiving a combination of TACE and Apatinib. Additionally, we have conducted a meticulous comparative analysis of these four scoring systems to discern their respective predictive capacities and efficacies in combined therapy. METHODS: Performing a retrospective analysis on the clinical data from 200 patients with intermediate and advanced HCC, we studied those who received TACE combined with Apatinib at the First Affiliated Hospital of the University of Science and Technology of China between June 2018 and December 2022. To identify the factors affecting survival, the study performed univariate and multivariate Cox regression analyses, with calculations of four different scores: HAP, Six-and-Twelve, Up to Seven, and ALBI. Lastly, Harrell's C-index was employed to compare the prognostic abilities of these scores. RESULTS: Cox proportional hazards model results revealed that the ALBI score, presence of portal vein tumor thrombus (PVTT, )and tumor size are independent determinants of prognostic survival. The Kaplan-Meier analyses showed significant differences in survival rates among patients classified by the HAP, Six-and-Twelve, Up to Seven, and ALBI scoring methods. Of the evaluated systems, the HAP scoring demonstrated greater prognostic precision, with a Harrell's C-index of 0.742, surpassing the alternative models (P < 0.05). In addition, an analysis of the area under the AU-ROC curve confirms the remarkable superiority of the HAP score in predicting short-term survival outcomes. CONCLUSION: Our study confirms the predictive value of HAP, Six-and-Twelve, Up to Seven, and ALBI scores in intermediate to advanced Hepatocellular Carcinoma (HCC) patients receiving combined Transarterial Chemoembolization (TACE) and Apatinib therapy. Notably, the HAP model excels in predicting outcomes for this specific HCC subgroup.

Liver abscess after drug-eluting bead transarterial chemoembolization for hepatic malignant tumors: Clinical features, pathogenesis, and management.

AIM: The study aimed to investigate the clinical features, incidence, pathogenesis, and management of liver abscess after drug-eluting bead transarterial chemoembolization (DEB-TACE) for primary and metastatic hepatic malignant tumors. METHODS: From June 2019 to June 2021, patients with liver abscess after DEB-TACE for primary and metastatic hepatic malignant tumors were reviewed and evaluated at our hospital. Demographic and clinical data, radiological findings, management approaches, and prognosis were retrospectively analyzed. RESULTS: In total, 419 DEB-TACE procedures were carried out in 314 patients with primary and metastatic liver tumors at our medical center. Twelve patients were confirmed to have liver abscesses after DEB-TACE through clinical manifestations, laboratory investigations, and imaging. In this study, the incidence of liver abscess was 3.82% per patient and 2.86% per DEB-TACE procedure. After percutaneous drainage and anti-inflammatory treatments, 10 patients recovered, and the remaining 2 patients died due to direct complications of liver abscess, such as sepsis and multiple organ failure. The mortality rate of liver abscesses after DEB-TACE was 16.7% (2/12). CONCLUSION: The incidence of liver abscess after DEB-TACE is relatively high and can have serious consequences, including death. Potential risk factors could include large tumor size, history of bile duct or tumor resection, history of diabetes, small DEB size (100-300 µm). Sensitive antibiotics therapy and percutaneous abscess aspiration/drainage are effective treatments for liver abscess after DEB-TACE.

Small molecule targeting CELF1 RNA-binding activity to control HSC activation and liver fibrosis.

CUGBP Elav-like family member 1 (CELF1), an RNA-binding protein (RBP), plays important roles in the pathogenesis of diseases such as myotonic dystrophy, liver fibrosis and cancers. However, targeting CELF1 is still a challenge, as RBPs are considered largely undruggable. Here, we discovered that compound 27 disrupted CELF1-RNA binding via structure-based virtual screening and biochemical assays. Compound 27 binds directly to CELF1 and competes with RNA for binding to CELF1. Compound 27 promotes IFN-γ secretion and suppresses TGF-ß1-induced hepatic stellate cell (HSC) activation by inhibiting CELF1-mediated IFN-γ mRNA decay. In vivo, compound 27 attenuates CCl4-induced murine liver fibrosis. Furthermore, the structure-activity relationship analysis was performed and compound 841, a derivative of compound 27, was identified as a selective CELF1 inhibitor. In conclusion, targeting CELF1 RNA-binding activity with small molecules was achieved, which provides a novel strategy for treating liver fibrosis and other CELF1-mediated diseases.

A multi-institutional study to predict the benefits of DEB-TACE and molecular targeted agent sequential therapy in unresectable hepatocellular carcinoma using a radiological-clinical nomogram.

OBJECTIVE: Exploring the efficacy of a Radiological-Clinical (Rad-Clinical) model in predicting prognosis of unresectable hepatocellular carcinoma (HCC) patients after drug eluting beads transcatheter arterial chemoembolization (DEB-TACE) to optimize the targeted sequential treatment. METHODS: In this retrospective analysis, we included 202 patients with unresectable HCC who received DEB-TACE treatment in 17 institutions from June 2018 to December 2022. Progression-free survival (PFS)-related radiomics features were computationally extracted from HCC patients to build a radiological signature (Rad-signature) model with least absolute shrinkage and selection operator regression. A Rad-Clinical model for postoperative PFS was further constructed according to the Rad-signature and clinical variables by Cox regression analysis. It was presented as a nomogram and evaluated by receiver operating characteristic curves, calibration curves, and decision curve analysis. And further evaluate the application value of Rad-Clinical model in clinical stages and targeted sequential therapy of HCC. RESULTS: Tumor size, Barcelona Clinic Liver Cancer (BCLC) stage, and radiomics score (Rad-score) were found to be independent risk factors for PFS after DEB-TACE treatment for unresectable HCC, with the Rad-Clinical model being the greatest predictor of PFS in these patients (hazard ratio: 2.08; 95% confidence interval: 1.56-2.78; P < 0.001) along with high 6 months, 12 months, 18 months, and 24 months area under the curves of 0.857, 0.810, 0.843, and 0.838, respectively. In addition, compared to the radiomics and clinical nomograms, the Radiological-Clinical nomogram also significantly improved the classification accuracy for PFS outcomes, based on the net reclassification improvement (45.2%, 95% CI 0.260-0.632, p < 0.05) and integrated discrimination improvement (14.9%, 95% CI 0.064-0.281, p < 0.05). Based on this model, low-risk patients had higher PFS than high-risk patients in BCLC-B and C stages (P = 0.021). Targeted sequential therapy for patients with high and low-risk HCC in BCLC-B stage exhibited significant benefits (P = 0.018, P = 0.012), but patients with high-risk HCC in BCLC-C stage did not benefit much (P = 0.052). CONCLUSION: The Rad-Clinical model may be favorable for predicting PFS in patients with unresectable HCC treated with DEB-TACE and for identifying patients who may benefit from targeted sequential therapy.

Targeted Protein Degradation via Lysosomes.

In the scope of targeted protein degradation (TPD), proteolysis-targeting chimeras (PROTACs), leveraging the ubiquitin-proteasome system, have been extensively studied. However, they are limited to the degradation of soluble and membrane proteins, excluding the aggregated and extracellular proteins and dysfunctional organelles. As an alternative protein degradation pathway, lysosomes serve as a feasible tool for accessing these untouched proteins and/or organelles by proteosomes. Here, we focus on reviewing the emerging lysosome-mediated TPD, such as AUTAC, ATTEC, AUTOTAC, LYTAC, and MoDE-A. Intracellular targets, such as soluble and aggregated proteins and organelles, can be degraded via the autophagy-lysosome pathway. Extracellular targets, such as membrane proteins, and secreted extracellular proteins can be degraded via the endosome-lysosome pathway. In addition, we summarize the mechanism and regulation of autophagy, available methods and assays for monitoring the autophagy process, and the recently developed chemical probes for perturbing the autophagy pathways.

Synthesis of Visible Light Excitable Carbon Dot Phosphor-Al2 O3 Hybrids for Anti-Counterfeiting and Information Encryption.

The preparation of room temperature phosphorescent carbon dots still faces great challenges, especially in the case of carbon dots endowed of visible-light excitable room temperature phosphorescence (RTP). To date, a limited number of substrates have been exploited to synthesize room temperature phosphorescent carbon dots, and most of them can emit RTP only in solid state. Here, the synthesis of a composite obtained from the calcination of green carbon dots (g-CDs) blended with aluminum hydroxide (Al(OH)3 ) is reported. The resultant hybrid material g-CDs@Al2 O3 exhibits blue fluorescence and green RTP emissions in an on/off switch process at 365 nm. Notably, this composite manifests strong resistance to extreme acid and basic conditions up to 30 days of treatment. The dense structure of Al2 O3 formed by calcination contributes to the phosphorescent emission of g-CDs. Surprisingly, g-CDs@Al2 O3 can also emit yellow RTP under irradiation with white light. The multicolor emissions can be employed for anti-counterfeiting and information encryption. This work provides a straightforward approach to produce room temperature phosphorescent carbon dots for a wide range of applications.

Strategies to improve the efficiency and quality of mutant breeding using heavy-ion beam irradiation.

Heavy-ion beam irradiation (HIBI) is useful for generating new germplasm in plants and microorganisms due to its ability to induce high mutagenesis rate, broad mutagenesis spectrum, and excellent stability of mutants. However, due to the random mutagenesis and associated mutant breeding modalities, it is imperative to improve HIBI-based mutant breeding efficiency and quality. This review discusses and summarizes the findings of existing theoretical and technical studies and presents a set of tandem strategies to enable efficient and high-quality HIBI-based mutant breeding practices. These strategies: adjust the mutation-inducing techniques, regulate cellular response states, formulate high-throughput screening schemes, and apply the generated superior genetic elements to genetic engineering approaches, thereby, improving the implications and expanding the scope of HIBI-based mutant breeding. These strategies aim to improve the mutagenesis rate, screening efficiency, and utilization of positive mutations. Here, we propose a model based on the integration of these strategies that would leverage the advantages of HIBI while compensating for its present shortcomings. Owing to the unique advantages of HIBI in creating high-quality genetic resources, we believe this review will contribute toward improving HIBI-based breeding.

Synthesis of Tetrahydro-5H-indolo[2,3-b]quinolines through Copper-Catalyzed Cascade Reactions of Aza-o-quinone Methides with Indoles.

A variety of tetrahydro-5H-indolo[2,3-b]quinolines were prepared in 40-97% yields through a copper(II)-catalyzed cascade reaction of aza-o-quinone methides generated in situ from 2-(chloromethyl)anilines and indoles. Experimental results showed that the reaction underwent double 1,4-additions and sequential intramolecular cyclization. The present method features broad substrate scope, good functional group tolerance, and easy gram scalable preparation of indolo[2,3-b]quinolines.

Biliary self-expandable metallic stent combined with iodine-125 seeds in the treatment of malignant biliary obstruction (Bismuth type I or II).

BACKGROUND: The purpose of this research was to evaluate the safety and efficacy of a self-expandable metallic stent (SEMS) combined with iodine-125 (125I) seeds in the treatment of Bismuth type I or II malignant biliary obstruction (MBO). METHODS: The clinical data of 74 cases of MBO treated with percutaneous SEMS combined with 125I seeds (combination group) and 81 cases of MBO treated with SEMS implantation alone (control group) in our hospital from January 2015 to December 2019 were retrospectively analyzed. The short-term and long-term efficacy of the two groups were compared. Multivariate Cox regression analysis was used to analyze the factors affecting the surgical efficacy and survival rate. RESULTS: The liver blood test results of both groups improved at one week and one month post-stent insertion. No significant difference was established in the short-term efficacy or complications between the two groups (P = NS). Improved stent patency was observed in the combined group, 9.01 ± 4.38 months versus 6.79 ± 3.13 months, respectively (P < 0.001). Improved survival was also noted in the combined group 12.08 ± 5.38 months and 9.10 ± 4.16 months, respectively (P < 0.001). Univariate and multivariate analyses showed that the type of biliary stent and liver metastasis were independent factors affecting survival. CONCLUSION: The implementation of SEMS combined with 125I seeds resulted in significantly longer stent patency and survival times than that of SEMS implantation alone, which is thus worthy of clinical promotion and application.

Chronicling changes in the somatosensory neurons after peripheral nerve injury.

Current drug discovery efforts focus on identifying lead compounds acting on a molecular target associated with an established pathological state. Concerted molecular changes that occur in specific cell types during disease progression have generally not been identified. Here, we used constellation pharmacology to investigate rat dorsal root ganglion neurons using two models of peripheral nerve injury: chronic constriction injury (CCI) and spinal nerve ligation (SNL). In these well-established models of neuropathic pain, we show that the onset of chronic pain is accompanied by a dramatic, previously unreported increase in the number of bradykinin-responsive neurons, with larger increases observed after SNL relative to CCI. To define the neurons with altered expression, we charted the temporal course of molecular changes following 1, 3, 6, and 14 d after SNL injury and demonstrated that specific molecular changes have different time courses during the progression to a pain state. In particular, ATP receptors up-regulated on day 1 postinjury, whereas the increase in bradykinin receptors was gradual after day 3 postinjury. We specifically tracked changes in two subsets of neurons: peptidergic and nonpeptidergic nociceptors. Significant increases occurred in ATP responses in nAChR-expressing isolectin B4+ nonpeptidergic neurons 1 d postinjury, whereas peptidergic neurons did not display any significant change. We propose that remodeling of ion channels and receptors occurs in a concerted and cell-specific manner, resulting in the appearance of bradykinin-responsive neuronal subclasses that are relevant to chronic pain.

Nephrotoxicity assessment of Esculentoside A using human-induced pluripotent stem cell-derived organoids.

Drug-induced nephrotoxicity is a leading cause of acute kidney injury (AKI). A major obstacle in predicting AKI is the lack of a comprehensive experimental model that mimics stable and physiologically relevant kidney functions and accurately reflects the changes a drug induces. Organoids derived from human-induced pluripotent stem cells (iPSCs) are promising models because of their reproducibility and similarity to the in vivo conditions. In this study, Esculentoside A, the triterpene saponin with the highest concentration isolated from the root of Phytolacca acinose Roxb., was used to induce kidney injury models in vivo and kidney organoids. Esculentoside A induced AKI in mice, together with pathological changes and enhanced apoptosis. Moreover, Esculentoside A damaged podocytes and proximal tubular endothelial cells in kidney organoids in a similar way as in vivo. We also found that treatment with 60 µM Esculentoside A induced the known biomarkers of kidney damage and inflammatory cytokines (such as kidney injury molecule (KIM-1), ß2-microglobulin (ß2-M), and cystatin C (CysC)) in the organoids, in which activation of Cleaved Caspase-3 was involved, possibly due to lowered mitochondrial membrane potential. In summary, this study strongly suggests using kidney organoids as a reliable platform to assess Chinese medicine-induced nephrotoxicity.

Circadian nuclear receptor Rev-erbα is expressed by platelets and potentiates platelet activation and thrombus formation.

AIMS: Adverse cardiovascular events have day/night patterns with peaks in the morning, potentially related to endogenous circadian clock control of platelet activation. Circadian nuclear receptor Rev-erbα is an essential and negative component of the circadian clock. To date, the expression profile and biological function of Rev-erbα in platelets have never been reported. METHODS AND RESULTS: Here, we report the presence and functions of circadian nuclear receptor Rev-erbα in human and mouse platelets. Both human and mouse platelet Rev-erbα showed a circadian rhythm that positively correlated with platelet aggregation. Global Rev-erbα knockout and platelet-specific Rev-erbα knockout mice exhibited defective in haemostasis as assessed by prolonged tail-bleeding times. Rev-erbα deletion also reduced ferric chloride-induced carotid arterial occlusive thrombosis, prevented collagen/epinephrine-induced pulmonary thromboembolism, and protected against microvascular microthrombi obstruction and infarct expansion in an acute myocardial infarction model. In vitro thrombus formation assessed by CD41-labelled platelet fluorescence intensity was significantly reduced in Rev-erbα knockout mouse blood. Platelets from Rev-erbα knockout mice exhibited impaired agonist-induced aggregation responses, integrin αIIbß3 activation, and α-granule release. Consistently, pharmacological inhibition of Rev-erbα by specific antagonists decreased platelet activation markers in both mouse and human platelets. Mechanistically, mass spectrometry and co-immunoprecipitation analyses revealed that Rev-erbα potentiated platelet activation via oligophrenin-1-mediated RhoA/ERM (ezrin/radixin/moesin) pathway. CONCLUSION: We provided the first evidence that circadian protein Rev-erbα is functionally expressed in platelets and potentiates platelet activation and thrombus formation. Rev-erbα may serve as a novel therapeutic target for managing thrombosis-based cardiovascular disease.

Applications of covalent chemistry in targeted protein degradation.

Proteolysis-targeting chimeras (PROTACs) and targeted covalent inhibitors (TCIs) are currently two exciting strategies in the fields of chemical biology and drug discovery. Extensive research in these two fields has been conducted, and significant progress in these fields has resulted in many clinical candidates, some of which have been approved by FDA. Recently, a novel concept termed covalent PROTACs that combine these two strategies has emerged and gained an increasing interest in the past several years. Herein, we briefly review and highlight the mechanism and advantages of TCIs and PROTACs, respectively, and the recent development of covalent PROTACs using irreversible and reversible covalent chemistry.

Casein kinase 1α 1 is involved in the progression of glioblastoma through HIF-1α-mediated autophagy.

Glioblastoma (GBM) is a malignant tumor prone to recurrence and resistant to conventional therapies. GBM cells show high autophagy activity, contributing to its rapid progression. Casein kinase 1 family, such as casein kinase 1α (CK1α), has shown its effect on autophagy by binding to the hypoxia-inducible factor-1α (HIF-1α). This study investigates the expression of CK1α and HIF-1α in healthy and GBM tissues and its relations with autophagy-related genes and GBM cell viability. The expressions of CK1α, HIF-1α, and autophagy-related proteins in normal tissues, GBM tissues, and GBM cell lines (U87MG, U251, U118-MG, LN229, and SHG44) were analyzed by qRT-PCR and Western blotting. In vitro, the U87MG cell line was transfected with pcDNA3.1-CK1α to enhance the expression of CK1α or both pcDNA3.1-CK1α and siRNA-HIF-1α. The expression of CK1α, HIF-1α, and autophagy-related proteins in GBM brain tissues and cell lines was higher than in normal brain tissues. In U87MG cells, enhanced CK1α expression upregulated the expression of HIF-1α and autophagy-related proteins and promoted cell proliferation. Inhibiting the expression of HIF-1α reduced the expression of autophagy-related proteins and decreased U87MG cell viability. Overexpressed CK1α positively regulates autophagy activity through the HIF-1α pathway. Inhibition of CK1α might be a potential therapeutic approach for glioblastoma therapy.NEW & NOTEWORTHY The study demonstrated that overexpressed CK1α positively regulated autophagy activity through the HIF-1α pathway to promote the progression. Thus, CK1α might be a potential treatment target for glioblastoma.

Unconventional Hysteretic Transition in a Charge Density Wave.

Hysteresis underlies a large number of phase transitions in solids, giving rise to exotic metastable states that are otherwise inaccessible. Here, we report an unconventional hysteretic transition in a quasi-2D material, EuTe_{4}. By combining transport, photoemission, diffraction, and x-ray absorption measurements, we observe that the hysteresis loop has a temperature width of more than 400 K, setting a record among crystalline solids. The transition has an origin distinct from known mechanisms, lying entirely within the incommensurate charge density wave (CDW) phase of EuTe_{4} with no change in the CDW modulation periodicity. We interpret the hysteresis as an unusual switching of the relative CDW phases in different layers, a phenomenon unique to quasi-2D compounds that is not present in either purely 2D or strongly coupled 3D systems. Our findings challenge the established theories on metastable states in density wave systems, pushing the boundary of understanding hysteretic transitions in a broken-symmetry state.

Synthesis of (Deoxy)difluoromethylated Phosphines by Reaction of R2P(O)H with TMSCF3 and Their Application in Cu(I) Clusters in Sonogashira Coupling.

R2PCF2H ligands and their R2P(O)CF2H precursors were synthesized from R2P(O)H with TMSCF3 by simply modulating the H2O concentration via deoxydifluoromethylation and difluoromethylation. The air sensitive R2PCF2H phosphines can be stabilized in Cu(I) clusters as ligands. Within these Cu(I) clusters, the Sonogashira cross-coupling reaction can proceed fast and efficiently using terminal alkynes and aryl iodides within 15 min at room temperature under air to give a variety of diaryl(alkyl)acetylenes in good yields (49 examples, yields of ≤99%). Six of the internal alkynes present in drug precursors can be obtained using this protocol in good yields. The mechanism is proposed on the basis of control experiments.