An efficient approach toward production of near-zigzag single-chirality carbon nanotubes.

Synthesizing single-walled carbon nanotubes (SWCNTs) with a narrow chirality distribution is essential for obtaining pure chirality materials through postgrowth sorting techniques. Using carbon monoxide chemical vapor deposition, we devise a ruthenium (Ru) catalyst supported by silica for the bulk production of SWCNTs containing only a few (n, m) species. The result is attributed to the limited carbon dissociation on the supported Ru clusters, favoring the growth of only small-diameter SWCNTs at comparable growth rates. The resulting materials expedite high-purity single chirality separation using gel chromatography, leading to unprecedented yields of 3.5% for (9, 1) and 5.2% for (9, 2) nanotubes, which surpass those separated from HiPco SWCNTs by two orders of magnitude. This work sheds light on the large-quantity synthesis of SWCNTs with enriched species beyond near-armchair ones for their high-yield separation.

KNSTRN Is a Prognostic Biomarker That Is Correlated with Immune Infiltration in Breast Cancer and Promotes Cell Cycle and Proliferation.

Kinetochore-localized astrin/SPAG5-binding protein (KNSTRN) promotes the progression of bladder cancer and lung adenocarcinoma. However, its expression and biological function in breast cancer remain largely unknown. Therefore, this study aimed to analyze KNSTRN expression, prognoses, correlation with immune infiltration, expression-associated genes, and regulated signaling pathways to characterize its role in regulating the cell cycle using both bioinformatics and in vitro functional experiments. Analyses of The Cancer Genome Atlas, Gene Expression Omnibus, TIMER, and The Human Protein Atlas databases revealed a significant upregulation of KNSTRN transcript and protein levels in breast cancer. Kaplan-Meier survival analyses demonstrated a significant association between high expression of KNSTRN and poor overall survival, relapse-free survival, post-progression survival, and distant metastases-free survival in patients with breast cancer. Furthermore, multivariate Cox regression analyses confirmed that KNSTRN is an independent prognostic factor for breast cancer. Immune infiltration analysis indicated a positive correlation between KNSTRN expression and T regulatory cell infiltration while showing a negative correlation with Tgd and natural killer cell infiltration. Gene set enrichment analysis along with single-cell transcriptome data analysis suggested that KNSTRN promoted cell cycle progression by regulating the expression of key cell cycle proteins. The overexpression and silencing of KNSTRN in vitro, respectively, promoted and inhibited the proliferation of breast cancer cells. The overexpression of KNSTRN enhanced the expression of key cell cycle regulators, including CDK4, CDK6, and cyclin D3, thereby accelerating the G1/S phase transition and leading to aberrant proliferation of breast cancer cells. In conclusion, our study demonstrates that KNSTRN functions as an oncogene in breast cancer by regulating immune response, promoting G1/S transition, and facilitating breast cancer cell proliferation. Moreover, KNSTRN has potential as a molecular biomarker for diagnostic and prognostic prediction in breast cancer.

Probing the critical nucleus size in tetrahydrofuran clathrate hydrate formation using surface-anchored nanoparticles.

Controlling the formation of clathrate hydrates is crucial for advancing hydrate-based technologies. However, the microscopic mechanism underlying clathrate hydrate formation through nucleation remains poorly elucidated. Specifically, the critical nucleus, theorized as a pivotal step in nucleation, lacks empirical validation. Here, we report uniform nanoparticles, e.g., graphene oxide (GO) nanosheets and gold or silver nanocubes with controlled sizes, as nanoprobes to experimentally measure the size of the critical nucleus of tetrahydrofuran (THF) clathrate hydrate formation. The capability of the nanoparticles in facilitating THF clathrate hydrate nucleation displays generally an abrupt change at a nanoparticle-size-determined specific supercooling. It is revealed that the free-energy barrier shows an abrupt change when the nanoparticles have an approximately the same size as that of the critical nucleus. Thus, it is inferred that THF clathrate hydrate nucleation involves the creation of a critical nucleus with its size being inversely proportional to the supercooling. By proving the existence and determining the supercooling-dependent size of the critical nucleus of the THF clathrate hydrates, this work brings insights in the microscopic pictures of the clathrate hydrate nucleation.

The diagnostic value of serum lncRNA CATG00000112921.1 as a marker of multiple myeloma.

BACKGROUND: Multiple myeloma (MM) is a malignant plasma cell disease. At present, numerous studies have shown that lncRNA plays a very important role in the occurrence, development and even drug resistance of multiple myeloma. It may become a potential diagnostic and prognostic marker of multiple myeloma and provide new ideas for targeted therapy. Based on the above research background, this study used gene chip technology to screen out the differentially expressed lncRNA in the serum of MM patients and healthy people, and verified more clinical serum samples to screen out the lncRNA with the largest difference as a biomarker for further research. METHOD: In this research, the data of hospitalized patients diagnosed with MM and healthy people in the Affiliated Hospital of Guangdong Medical University were retrospectively collected. The lncRNA expression profile of serum samples from patients with multiple myeloma and healthy controls was analyzed by lncRNA chip technology. The serum samples were verified by real-time fluorescence quantitative PCR, and the candidate diagnostic markers were screened out. The ROC working curve was drawn to evaluate the diagnostic efficacy of the candidate markers and to determine their stability at different temperatures and time. RESULT: A total of 44 MM patients and 37 healthy people were involved in this research. Among them, 4 patients with MM and 4 patients with HD were sent for microarray analysis. According to Fold Change ≥ 2 and P < 0.05, a total of 17 differentially expressed lncRNA molecules were screened, of which 9 were up-regulated RNA molecules and 8 were down-regulated RNA molecules. Through real-time fluorescence quantitative PCR verification, it was found that lncRNA CATG00000112921.1 was highly expressed in the healthy control group and diminished in patients with multiple myeloma, P < 0.001. The ROC curve demonstrated that the area under the curve (AUC) was 0.749, the sensitivity was 0.636, the specificity was 0.789, and the 95 % CI was 0.636-0.862 (P < 0.001). In addition, in order to verify the effects of temperature, time and repeated freezing and thawing on lncRNA, it was placed at 25°C, 4°C, -20°C, -80°C for 0 h, 24 h, 48 h, 72 h, and placed at-80°C repeated freezing and thawing 0 times, 2 times, 4 times, 8 times, and the expression level was not significantly changed. CONCLUSION: Serum lncRNA CATG00000112921.1 may be a potential candidate diagnostic marker for multiple myeloma. The ROC curve shows that it has good diagnostic value, and its high stability at different temperatures and different times is a required condition for becoming a diagnostic marker. As far as we know, this is the first study in the world to find differential expression of lncRNA CATG00000112921.1 in peripheral serum of healthy people and newly diagnosed multiple myeloma patients. This study also highlights the application of gene chip technology in screening differentially expressed genes.

Roles of PPAR activation in cancer therapeutic resistance: Implications for combination therapy and drug development.

Therapeutic resistance is a major obstacle to successful treatment or effective containment of cancer. Peroxisome proliferator-activated receptors (PPARs) play an essential role in regulating energy homeostasis and determining cell fate. Despite of the pleiotropic roles of PPARs in cancer, numerous studies have suggested their intricate relationship with therapeutic resistance in cancer. In this review, we provided an overview of the roles of excessively activated PPARs in promoting resistance to modern anti-cancer treatments, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy. The mechanisms through which activated PPARs contribute to therapeutic resistance in most cases include metabolic reprogramming, anti-oxidant defense, anti-apoptosis signaling, proliferation-promoting pathways, and induction of an immunosuppressive tumor microenvironment. In addition, we discussed the mechanisms through which activated PPARs lead to multidrug resistance in cancer, including drug efflux, epithelial-to-mesenchymal transition, and acquisition and maintenance of the cancer stem cell phenotype. Preliminary studies investigating the effect of combination therapies with PPAR antagonists have suggested the potential of these antagonists in reversing resistance and facilitating sustained cancer management. These findings will provide a valuable reference for further research on and clinical translation of PPAR-targeting treatment strategies.

KCNN1 promotes proliferation and metastasis of breast cancer via ERLIN2-mediated stabilization and K63-dependent ubiquitination of Cyclin B1.

Potassium Calcium-Activated Channel Subfamily N1 (KCNN1), an integral membrane protein, is thought to regulate neuronal excitability by contributing to the slow component of synaptic after hyperpolarization. However, the role of KCNN1 in tumorigenesis has been rarely reported, and the underlying molecular mechanism remains unclear. Here, we report that KCNN1 functions as an oncogene in promoting breast cancer cell proliferation and metastasis. KCNN1 was overexpressed in breast cancer tissues and cells. The pro-proliferative and pro-metastatic effects of KCNN1 were demonstrated by CCK8, clone formation, Edu assay, wound healing assay and transwell experiments. Transcriptomic analysis using KCNN1 overexpressing cells revealed that KCNN1 could regulate key signaling pathways affecting the survival of breast cancer cells. KCNN1 interacts with ERLIN2 and enhances the effect of ERLIN2 on Cyclin B1 stability. Overexpression of KCNN1 promoted the protein expression of Cyclin B1, enhanced its stability and promoted its K63 dependent ubiquitination, while knockdown of KCNN1 had the opposite effects on Cyclin B1. Knockdown (or overexpression) ERLNI2 partially restored Cyclin B1 stability and K63 dependent ubiquitination induced by overexpression (or knockdown) of KCNN1. Knockdown (or overexpression) ERLIN2 also partially neutralizes the effects of overexpression (or knockdown) KCNN1-induced breast cancer cell proliferation, migration and invasion. In paired breast cancer clinical samples, we found a positive expression correlations between KCNN1 and ERLIN2, KCNN1 and Cyclin B1, as well as ERLIN2 and Cyclin B1. In conclusion, this study reveals, for the first time, the role of KCNN1 in tumorigenesis and emphasizes the importance of KCNN1/ERLIN2/Cyclin B1 axis in the development and metastasis of breast cancer.

Rapid Detection of blaKPC in Carbapenem-Resistant Enterobacterales Based on CRISPR/Cas13a.

Klebsiella pneumoniae carbapenemase (KPC) is a crucial enzyme that causes carbapenem resistance in Enterobacterales, and infections by these "superbugs" are extremely challenging to treat. Therefore, there is a pressing need for a rapid and accurate KPC detection test to control the prevalence of carbapenem-resistant Enterobacterales (CREs). In this study, we established a novel method for detection of blaKPC, the gene responsible for encoding KPC, based on a recombinase polymerase amplification (RPA) and a CRISPR/Cas13a reaction coupled to fluorophore activation (termed RPA-Cas13a assay). We carefully selected a pair of optimal amplification primers for blaKPC and achieved a lower limit of detection of approximately 2.5 copies/µL by repeatedly amplifying a recombinant plasmid containing blaKPC. The RPA-Cas13a assay demonstrated a sensitivity of 96.5% and specificity of 100% when tested on 57 blaKPC-positive CRE strains, which were confirmed by DNA sequencing. Moreover, in 311 sputum samples, the theoretical antibiotic resistance characteristics of blaKPC-positive strains obtained by the RPA-Cas13a assay were highly consistent with the results of antibiotic susceptibility test (Kappa = 0.978 > 0.81, P < 0.01). In conclusion, the RPA-Cas13a system is a simple and one-hour efficient technology for the detection of a potentially fatal antibiotic resistance gene.

Predicting thalassemia using deep neural network based on red blood cell indices.

BACKGROUND AND OBJECTIVE: The traditional statistical screening method for thalassemia based on red blood cell (RBC) indices is being replaced by machine learning. Here, we developed deep neural networks (DNNs) that outperformed the traditional method for predicting thalassemia. METHOD: Using a dataset of 8693 records comprising genetic tests and other 11 features we constructed 11 DNN models and 4 traditional statistical models and then compared their performances and analysed feature importance for interpreting DNN models. RESULTS: The area under the receiver operating characteristic curve, accuracy, Youden's index, F1 score, sensitivity, specificity, positive predictive value and negative predictive value, were 0.960, 0.897, 0.794, 0.897, 0.883, 0.911, 0.914, and 0.882, respectively, for our best model, and compared with the traditional statistical model based on the mean corpuscular volume, these values were increased by 10.22%, 10.09%, 26.55%, 8.92%, 4.13%, 16.90%, 13.86% and 6.07%, respectively, and by 15.38%, 11.70%, 31.70%, 9.89%, 3.05%, 22.13%, 17.11% and 5.94%, respectively, for the mean cellular haemoglobin model. The DNN model performance will reduce without age, RBC distribution width (RDW), sex, or both WBC and PLT. CONCLUSIONS: Our DNN model outperformed the current screening model. In 8 features, RDW and age were the most useful, followed by sex and the combination of WBC and PLT, the remaining nearly useless.

Epstein-Barr Virus Envelope Glycoprotein gp110 Inhibits IKKi-Mediated Activation of NF-κB and Promotes the Degradation of ß-Catenin.

Epstein-Barr virus (EBV) infects host cells and establishes a latent infection that requires evasion of host innate immunity. A variety of EBV-encoded proteins that manipulate the innate immune system have been reported, but whether other EBV proteins participate in this process is unclear. EBV-encoded envelope glycoprotein gp110 is a late protein involved in virus entry into target cells and enhancement of infectivity. Here, we reported that gp110 inhibits RIG-I-like receptor pathway-mediated promoter activity of interferon-ß (IFN-ß) as well as the transcription of downstream antiviral genes to promote viral proliferation. Mechanistically, gp110 interacts with the inhibitor of NF-κB kinase (IKKi) and restrains its K63-linked polyubiquitination, leading to attenuation of IKKi-mediated activation of NF-κB and repression of the phosphorylation and nuclear translocation of p65. Additionally, gp110 interacts with an important regulator of the Wnt signaling pathway, ß-catenin, and induces its K48-linked polyubiquitination degradation via the proteasome system, resulting in the suppression of ß-catenin-mediated IFN-ß production. Taken together, these results suggest that gp110 is a negative regulator of antiviral immunity, revealing a novel mechanism of EBV immune evasion during lytic infection. IMPORTANCE Epstein-Barr virus (EBV) is a ubiquitous pathogen that infects almost all human beings, and the persistence of EBV in the host is largely due to immune escape mediated by its encoded products. Thus, elucidation of EBV's immune escape mechanisms will provide a new direction for the design of novel antiviral strategies and vaccine development. Here, we report that EBV-encoded gp110 serves as a novel viral immune evasion factor, which inhibits RIG-I-like receptor pathway-mediated interferon-ß (IFN-ß) production. Furthermore, we found that gp110 targeted two key proteins, inhibitor of NF-κB kinase (IKKi) and ß-catenin, which mediate antiviral activity and the production of IFN-ß. gp110 inhibited K63-linked polyubiquitination of IKKi and induced ß-catenin degradation via the proteasome, resulting in decreased IFN-ß production. In summary, our data provide new insights into the EBV-mediated immune evasion surveillance strategy.

Preparing high-concentration individualized carbon nanotubes for industrial separation of multiple single-chirality species.

Industrial production of single-chirality carbon nanotubes is critical for their applications in high-speed and low-power nanoelectronic devices, but both their growth and separation have been major challenges. Here, we report a method for industrial separation of single-chirality carbon nanotubes from a variety of raw materials with gel chromatography by increasing the concentration of carbon nanotube solution. The high-concentration individualized carbon nanotube solution is prepared by ultrasonic dispersion followed by centrifugation and ultrasonic redispersion. With this technique, the concentration of the as-prepared individualized carbon nanotubes is increased from about 0.19 mg/mL to approximately 1 mg/mL, and the separation yield of multiple single-chirality species is increased by approximately six times to the milligram scale in one separation run with gel chromatography. When the dispersion technique is applied to an inexpensive hybrid of graphene and carbon nanotubes with a wide diameter range of 0.8-2.0 nm, and the separation yield of single-chirality species is increased by more than an order of magnitude to the sub-milligram scale. Moreover, with present separation technique, the environmental impact and cost of producing single-chirality species are greatly reduced. We anticipate that this method promotes industrial production and practical applications of single-chirality carbon nanotubes in carbon-based integration circuits.

Heterovalent-doping-enabled atom-displacement fluctuation leads to ultrahigh energy-storage density in AgNbO3-based multilayer capacitors.

Dielectric capacitors with high energy storage performance are highly desired for next-generation advanced high/pulsed power capacitors that demand miniaturization and integration. However, the poor energy-storage density that results from the low breakdown strength, has been the major challenge for practical applications of dielectric capacitors. Herein, we propose a heterovalent-doping-enabled atom-displacement fluctuation strategy for the design of low-atom-displacements regions in the antiferroelectric matrix to achieve the increase in breakdown strength and enhancement of the energy-storage density for AgNbO3-based multilayer capacitors. An ultrahigh breakdown strength ~1450 kV·cm-1 is realized in the Sm0.05Ag0.85Nb0.7Ta0.3O3 multilayer capacitors, especially with an ultrahigh Urec ~14 J·cm-3, excellent η ~ 85% and PD,max ~ 102.84 MW·cm-3, manifesting a breakthrough in the comprehensive energy storage performance for lead-free antiferroelectric capacitors. This work offers a good paradigm for improving the energy storage properties of antiferroelectric multilayer capacitors to meet the demanding requirements of advanced energy storage applications.

Chirality-dependent electrical transport properties of carbon nanotubes obtained by experimental measurement.

Establishing the relationship between the electrical transport properties of single-wall carbon nanotubes (SWCNTs) and their structures is critical for the design of high-performance SWCNT-based electronic and optoelectronic devices. Here, we systematically investigated the effect of the chiral structures of SWCNTs on their electrical transport properties by measuring the performance of thin-film transistors constructed by eleven distinct (n, m) single-chirality SWCNT films. The results show that, even for SWCNTs with the same diameters but different chiral angles, the difference in the on-state current or carrier mobility could reach an order of magnitude. Further analysis indicates that the electrical transport properties of SWCNTs have strong type and family dependence. With increasing chiral angle for the same-family SWCNTs, Type I SWCNTs exhibit increasing on-state current and mobility, while Type II SWCNTs show the reverse trend. The differences in the electrical properties of the same-family SWCNTs with different chiralities can be attributed to their different electronic band structures, which determine the contact barrier between electrodes and SWCNTs, intrinsic resistance and intertube contact resistance. Our present findings provide an important physical basis for performance optimization and application expansion of SWCNT-based devices.

Epstein-Barr virus envelope glycoprotein 110 inhibits NF-κB activation by interacting with NF-κB subunit p65.

Epstein-Barr virus (EBV) is a member of the lymphotropic virus family and is highly correlated with some human malignant tumors. It has been reported that envelope glycoprotein 110 (gp110) plays an essential role in viral fusion, DNA replication, and nucleocapsid assembly of EBV. However, it has not been established whether gp110 is involved in regulating the host's innate immunity. In this study, we found that gp110 inhibits tumor necrosis factor α-mediated NF- κB promoter activity and the downstream production of NF- κB-regulated cytokines under physiological conditions. Using dual-luciferase reporter assays, we showed that gp110 might impede the NF-κB promoter activation downstream of NF-κB transactivational subunit p65. Subsequently, we used coimmunoprecipitation assays to demonstrate that gp110 interacts with p65 during EBV lytic infection, and that the C-terminal cytoplasmic region of gp110 is the key interaction domain with p65. Furthermore, we determined that gp110 can bind to the N-terminal Rel homologous and C-terminal domains of p65. Alternatively, gp110 might not disturb the association of p65 with nontransactivational subunit p50, but we showed it restrains activational phosphorylation (at Ser536) and nuclear translocation of p65, which we also found to be executed by the C-terminal cytoplasmic region of gp110. Altogether, these data suggest that the surface protein gp110 may be a vital component for EBV to antagonize the host's innate immune response, which is also helpful for revealing the infectivity and pathogenesis of EBV.

SLAMF7 regulates the inflammatory response in macrophages during polymicrobial sepsis.

Uncontrolled inflammation occurred in sepsis results in multiple organ injuries and shock, which contributes to the death of patients with sepsis. However, the regulatory mechanisms that restrict excessive inflammation are still elusive. Here, we identified an Ig-like receptor called signaling lymphocyte activation molecular family 7 (SLAMF7) as a key suppressor of inflammation during sepsis. We found that the expression of SLAMF7 on monocytes/macrophages was significantly elevated in patients with sepsis and in septic mice. SLAMF7 attenuated TLR-dependent MAPK and NF-κB signaling activation in macrophages by cooperating with Src homology 2-containing inositol-5'­phosphatase 1 (SHIP1). Furthermore, SLAMF7 interacted with SHIP1 and TNF receptor-associated factor 6 (TRAF6) to inhibit K63 ubiquitination of TRAF6. In addition, we found that tyrosine phosphorylation sites within the intracellular domain of SLAMF7 and the phosphatase domain of SHIP1 were indispensable for the interaction between SLAMF7, SHIP1, and TRAF6 and SLAMF7-mediated modulation of cytokine production. Finally, we demonstrated that SLAMF7 protected against lethal sepsis and endotoxemia by downregulating macrophage proinflammatory cytokines and suppressing inflammation-induced organ damage. Taken together, our findings reveal a negative regulatory role of SLAMF7 in polymicrobial sepsis, thus providing sights into the treatment of sepsis.

LncRNA T376626 is a promising serum biomarker and promotes proliferation, migration, and invasion via binding to LAMC2 in triple-negative breast cancer.

PURPOSE: Circulating long noncoding RNAs (lncRNAs) have been reported to serve as biomarkers for cancer diagnosis. Here, we identified the clinical diagnostic value and biological function of lncRNA T376626 in triple-negative breast cancer (TNBC). METHOD: A genome-wide lncRNA microarray was used to screen promising serum-based lncRNA biomarkers. The expression of candidate serum lncRNAs was validated in 282 breast cancer (BC) patients and 78 healthy subjects. The diagnostic value of serum lncRNA T376626 was determined by receiver operating characteristic (ROC) curve. RNA fluorescent in situ hybridization (FISH) and RNAScope ISH assays were conducted to examine the expression and localization of lncRNA T376626 in TNBC cells and BC tissues. Kaplan-Meier analysis was conducted to evaluate the relationship between lncRNA T376626 and BC patients' overall survival (OS) rate. CCK-8, colony-forming, wound healing and Transwell assays were performed to investigate the biological function of lncRNA T376626 on cell proliferation, migration, and invasion in two TNBC cell lines. Cell apoptosis-, cell cycle- and epithelial-mesenchymal transition (EMT)-related biomarkers were quantified by western blots. The lncRNA T376626 binding proteins were screened and identified by RNA pulldown. RESULTS: LncRNA T376626 level was significantly higher in TNBC serums and tissues. Higher levels of lncRNA T376626 were positively associated with a higher pathological differentiation stage, more aggressive molecular subtype, and poor prognosis in BC and TNBC patients. The area under the curve (AUC) of serum lncRNA T376626 was 0.842. Overexpression (Knockdown) of lncRNA T376626 significantly promoted (inhibited) TNBC cell proliferation, migration, and invasion, possibly by regulating several cell cycle, cell apoptosis and EMT biomarkers. LAMC2 were identified as lncRNA T376626-binding proteins. LAMC2 facilitated TNBC proliferation and metastasis through lncRNA T376626. CONCLUSIONS: LncRNA T376626 may serve as a TNBC serum-based diagnostic and prognostic biomarker and play an oncogenic role in TNBC progression through binding to LAMC2.

Sp1-Induced SETDB1 Overexpression Transcriptionally Inhibits HPGD in a ß-Catenin-Dependent Manner and Promotes the Proliferation and Metastasis of Gastric Cancer.

PURPOSE: Gastric cancer (GC) has high morbidity and mortality, the cure rate of surgical treatment and drug chemotherapy is not ideal. Therefore, development of new treatment strategies is necessary. We aimed to identify the mechanism underlying Sp1 regulation of GC progression. METHODS AND METHODS: The levels of Sp1, ß-catenin, SET domain bifurcated 1 (SETDB1), and 15-hydroxyprostaglandin dehydrogenase (HPGD) were detected by quantitative reverse transcription polymerase chain reaction and western blot analysis. The targets of SETDB1 were predicted by AnimalTFDB, and dual-luciferase reporter assay was used for confirming the combination of Sp1, ß-catenin, and SETDB1. HGC27 or AGS cells (1×106 cells/mouse) were injected into mice via the caudal vein for GC model establishment. The level of Ki67 was detected using immunohistochemistry, and hematoxylin and eosin staining was performed for evaluating tumor metastasis in mice with GC. RESULTS: HPGD was inhibited, while the protein levels of Sp1, ß-catenin, and SETDB1 were up-regulated in GC tissues and cell lines. HPGD overexpression or SETDB1 silencing inhibited the proliferation, invasion, and migration of GC cells, and Sp1 regulated the proliferation, invasion, and migration of GC cells in a ß-catenin-dependent manner. Furthermore, HPGD served as a target of SETDB1, and it was negatively regulated by SETDB1; additionally, Sp1 and ß-catenin bound to the SETDB1 promoter and negatively regulated HPGD expression. We proved that Sp1 regulated GC progression via the SETDB1/HPGD axis. CONCLUSIONS: Our findings revealed that Sp1 transcriptionally inhibited HPGD via SETDB1 in a ß-catenin-dependent manner and promoted the proliferation and metastasis of GC cells.

Role of an Ice Surface in the Photoreaction of Coumarins.

Ice affects many chemical reactions in nature, which greatly influences the atmosphere, climate, and life. However, the exact mechanism of ice in these chemical reactions remains elusive. For example, it is still an open question as to whether ice can act as a catalyst to greatly enhance the reactivity and selectivity, which is essential for the production of some natural compounds in our planet. Here, we discover that ice can lead to high efficiency and stereoselectivity of the [2 + 2] photodimerization of coumarin and its derivatives. The conversion of the [2 + 2] photodimerization of coumarins enhanced by ice is dozens of times higher than that in the unfrozen saturated solution, and the reaction displays a high syn-head-head stereoselectivity (>95%) in comparison with those in the absence of the ice. Note that almost no reaction occurs in the crystal powder and melt of the coumarins, indicating that the role of ice in the photodimerization reaction is not simply due to the usual mechanisms found in the freezing concentration. We further reveal that the reaction rate is found to be proportional to the total area of the ice surface and follows Michaelis-Menten-like kinetics, indicating that the ice surface catalyzes the reaction. Molecular dynamics simulations demonstrate that ice surfaces can induce reactants to form a two-dimensional liquid-crystal-ordered layer with a suitable intermolecular distance and unique side-by-side packing, facilitating stereoselective photodimerization for syn-head-head dimers. These findings give evidence that ice-surface-induced molecular assembly may play an important role in atmospheric heterogeneous photoreaction processes.

ZNF276 promotes the malignant phenotype of breast carcinoma by activating the CYP1B1-mediated Wnt/ß-catenin pathway.

Zinc finger proteins (ZNFs) have been demonstrated to participate extensively in breast cancer progression by functioning as transcription factors, but there are still a variety of ZNFs whose biological mechanisms remain unknown. Here, we show that zinc finger protein 276 (ZNF276) is highly expressed in breast cancer tissues and cell lines. Higher level of ZNF276 correlated with poor prognosis. Gain-of and loss-of function suggested that ZNF276 is essential for the proliferation, migration and invasion of breast cancer cells in vitro and metastasis in vivo. RNA-sequencing and CUT&Tag assay revealed that ZNF276 controlled a variety of growth and metastasis-related genes expression. ZNF276 transcriptionally promoted the expression of CYP1B1 by directly binds to the promoter region of the CYP1B1 through its C2H2 domain. ZNF276 facilitated the translocation of ß-catenin from cytoplasm to nucleus through CYP1B1, leading to the upregulation of cyclin D1 and c-Myc, and the activation of the Wnt/ß-catenin pathway. Knockdown of CYP1B1 significantly blocked the ZNF276-mediated effects on cell proliferation, migration and invasion. Lastly, ZNF276 interacted with MAGEB2 which enhanced the binding of ZNF276 at the CYP1B1 promoter, promoted CYP1B1 expression and Wnt signaling activation. Collectively, these findings highlight the oncogenic role of ZNF276 on breast cancer cell proliferation and metastasis. Targeting ZNF276/MAGEB2 axis may serve as a potential therapeutic strategy for breast cancer patients.

Triple quantitative detection of three inflammatory biomarkers with a biotin-streptavidin-phycoerythrin based lateral flow immunoassay.

Quantified inflammatory biomarkers are effective clinical strategy for correct and reasonable drug treatment. In the study, a triple lateral flow immunoassay (triple LFIA) had firstly been developed for specific and simultaneous detection of three pivotal inflammatory biomarkers (PCT, CRP and SAA) via biotin-streptavidin-phycoerythrin signal amplification system in one strip. The developed triple LFIA adopted phycoerythrin (PE) as chromophore to eliminate auto-fluorescence interference from plasma biomolecules and anti-PE mAb as single control line to reduce the nonspecific adsorption, which featured particular advantages in high sensitivity and specificity in a large range of analyte concentrations with the LODs of 0.106 ng/mL for PCT, 0.345 µg/mL for CRP and 3.112 µg/mL SAA, respectively. And the linear quantitative detection ranges were from 0.106 to 100 ng/mL, from 0.345 to 200 µg/mL, and from 3.112 to 200 µg/mL, respectively. Compared to commercial chemiluminescence immunoassay method, the correlations for tested PCT, CRP and SAA in 108 clinical samples were 0.989, 0.987 and 0.988, respectively. In summary, we had proposed a rapid and accurate plasma detection to measure inflammation factors, which facilitated the clinical value to achieve precise treatment.