The Higgs boson turns ten.

The discovery of the Higgs boson, ten years ago, was a milestone that opened the door to the study of a new sector of fundamental physical interactions. We review the role of the Higgs field in the Standard Model of particle physics and explain its impact on the world around us. We summarize the insights into Higgs physics revealed so far by ten years of work, discuss what remains to be determined and outline potential connections of the Higgs sector with unsolved mysteries of particle physics.

Aberrant degree centrality profiles during rumination in major depressive disorder.

Rumination is closely linked to the onset and maintenance of major depressive disorder (MDD). Prior neuroimaging studies have identified the association between self-reported rumination trait and the functional coupling among a network of brain regions using resting-state functional magnetic resonance imaging (MRI). However, little is known about the underlying neural circuitry mechanism during active rumination in MDD. Degree centrality (DC) is a simple metric to denote network integration, which is critical for higher-order psychological processes such as rumination. During an MRI scan, individuals with MDD (N = 45) and healthy controls (HC, N = 46) completed a rumination state task. We examined the interaction effect between the group (MDD vs. HC) and condition (rumination vs. distraction) on vertex-wise DC. We further characterized the identified brain region's functional involvement with Neurosynth and BrainMap. Network-wise seed-based functional connectivity (FC) analysis was also conducted for the identified region of interest. Finally, exploratory correlation analysis was conducted between the identified region of interest's network FCs and self-reported in-scanner affect levels. We found that a left superior frontal gyrus (SFG) region, generally overlapped with the frontal eye field, showed a significant interaction effect. Further analysis revealed its involvement with executive functions. FCs between this region, the frontoparietal, and the dorsal attention network (DAN) also showed significant interaction effects. Furthermore, its FC to DAN during distraction showed a marginally significant negative association with in-scanner affect level at the baseline. Our results implicated an essential role of the left SFG in the rumination's underlying neural circuitry mechanism in MDD and provided novel evidence for the conceptualization of rumination in terms of impaired executive control.

Differential Diagnosis of IgG4-related Pancreatitis and Pancreatic Cancer by MRI Features and Its Correlation with Serum IgG4 Level.

It was to analyze the diagnostic value of MRI in immunoglobulin G (IgG4)-related autoimmune pancreatitis (AIP) and pancreatic cancer (PC) and its relationship with serum IgG4 level. 35 patients with IgG4-related AIP (group A1) and 50 patients with PC (group A2) were enrolled. MRI was performed to determine serum IgG4 levels. Spearsman was used to analyze the relationship between MRI characteristics and serum IgG4 level. It was found that patients in group A1 showed double duct sign (DDS), pancreatic duct (PD) perforation sign, the proportion of main PD truncation, and main PD diameter/pancreatic parenchymal width ratio, which were different from those of patients in group A2 (P < 0.05). MRI had a sensitivity (Sen) of 88%, specificity (Spe) of 91.43%, accuracy (Acc) of 89.41%, positive predictive value (PPV) of 0.936, and negative predictive value(NPV) of 0.842 for the diagnosis of IgG4-related AIP and PC. Serum IgG4 levels were significantly negatively correlated with DDS and main PD truncation, significantly positively correlated with PD penetration sign, and extremely significantly negatively correlated with main PD diameter/pancreatic parenchymal width (P < 0.001). The results showed that MRI had high sensitivity and specificity for differentiating IgG4-related AIP from PC, and the diagnostic effect was good, which had a high correlation with serum IgG4 levels in patients.

The muon Smasher's guide.

We lay out a comprehensive physics case for a future high-energy muon collider, exploring a range of collision energies (from 1 to 100 TeV) and luminosities. We highlight the advantages of such a collider over proposed alternatives. We show how one can leverage both the point-like nature of the muons themselves as well as the cloud of electroweak radiation that surrounds the beam to blur the dichotomy between energy and precision in the search for new physics. The physics case is buttressed by a range of studies with applications to electroweak symmetry breaking, dark matter, and the naturalness of the weak scale. Furthermore, we make sharp connections with complementary experiments that are probing new physics effects using electric dipole moments, flavor violation, and gravitational waves. An extensive appendix provides cross section predictions as a function of the center-of-mass energy for many canonical simplified models.

Unambiguously Testing Positivity at Lepton Colliders.

The diphoton channel at lepton colliders, e^{+}e^{-}(µ^{+}µ^{-})→γγ, has a remarkable feature that the leading new physics contribution comes only from dimension-eight operators. This contribution is subject to a set of positivity bounds, derived from the fundamental principles of quantum field theory, such as unitarity, locality, analyticity and Lorentz invariance. These positivity bounds are thus applicable to the most direct observable: the diphoton cross section. This unique feature provides a clear, robust, and unambiguous test of these principles. We estimate the capability of various future lepton colliders in probing the dimension-eight operators and testing the positivity bounds in this channel. We show that positivity bounds can lift certain flat directions among the effective operators and significantly change the perspectives of a global analysis. We also discuss the positivity bounds of the Zγ/ZZ processes which are related to the γγ ones, but are more complicated due to the massive Z boson.

Comprehensive analysis of CXCR family members in lung adenocarcinoma with prognostic values.

BACKGROUND: The expression profiles and molecular mechanisms of CXC chemokine receptors (CXCRs) in Lung adenocarcinoma (LUAD) have been extensively explored. However, the comprehensive prognostic values of CXCR members in LUAD have not yet been clearly identified. METHODS: Multiple available datasets, including Oncomine datasets, the cancer genome atlas (TCGA), HPA platform, GeneMANIA platform, DAVID platform and the tumor immune estimation resource (TIMER) were used to detect the expression of CXCRs in LUAD, as well as elucidate the significance and value of novel CXCRs-associated genes and signaling pathways in LUAD. RESULTS: The mRNA and/or protein expression of CXCR1, CXCR2, CXCR3, CXCR4, CXCR5 and CXCR6 displayed predominantly decreased in LUAD tissues as compared to normal tissues. On the contrary, compared with the normal tissues, the expression of CXCR7 was significantly increased in LUAD tissues. Subsequently, we constructed a network including CXCR family members and their 20 related genes, and the related GO functions assay showed that CXCRs connected with these genes participated in the process of LUAD through several signal pathways including Chemokine signaling pathway, Cytokine-cytokine receptor interaction and Neuroactive ligand-receptor interaction. TCGA and Timer platform revealed that the mRNA expression of CXCR family members was significantly related to individual cancer stages, cancer subtypes, patient's gender and the immune infiltration level. Finally, survival analysis showed that low mRNA expression levels of CXCR2 (HR = 0.661, and Log-rank P = 1.90e-02), CXCR3 (HR = 0.674, and Log-rank P = 1.00e-02), CXCR4 (HR = 0.65, and Log-rank P = 5.01e-03), CXCR5 (HR = 0.608, and Log-rank P = 4.80e-03) and CXCR6 (HR = 0.622, and Log-rank P = 1.85e-03) were significantly associated with shorter overall survival (OS), whereas high CXCR7 mRNA expression (HR = 1.604, and Log-rank P = 4.27e-03) was extremely related with shorter OS in patients. CONCLUSION: Our findings from public databases provided a unique insight into expression characteristics and prognostic values of CXCR members in LUAD, which would be benefit for the understanding of pathogenesis, diagnosis, prognosis prediction and targeted treatment in LUAD.

SemSeq4FD: Integrating global semantic relationship and local sequential order to enhance text representation for fake news detection.

The wide spread of fake news has caused huge losses to both governments and the public. Many existing works on fake news detection utilized spreading information like propagators profiles and the propagation structure. However, such methods face the difficulty of data collection and cannot detect fake news at the early stage. An alternative approach is to detect fake news solely based on its content. Early content-based methods rely on manually designed linguistic features. Such shallow features are domain-dependent, and cannot easily be generalized to cross-domain data. Recently, many natural language processing tasks resort to deep learning methods to learn word, sentence, and document representations. In this paper, we propose a novel graph-based neural network model named SemSeq4FD for early fake news detection based on enhanced text representations. In SemSeq4FD, we model the global pair-wise semantic relations between sentences as a complete graph, and learn the global sentence representations via a graph convolutional network with self-attention mechanism. Considering the importance of local context in conveying the sentence meaning, we employ a 1D convolutional network to learn the local sentence representations. The two representations are combined to form the enhanced sentence representations. Then a LSTM-based network is used to model the sequence of enhanced sentence representations, yielding the final document representation for fake news detection. Experiments conducted on four real-world datasets in English and Chinese, including cross-source and cross-domain datasets, demonstrate that our model can outperform the state-of-the-art methods.

Reexamining the Solar Axion Explanation for the XENON1T Excess.

The XENON1T collaboration has observed an excess in electronic recoil events below 5 keV over the known background, which could originate from beyond-the-standard-model physics. The solar axion is a well-motivated model that has been proposed to explain the excess, though it has tension with astrophysical observations. The axions traveling from the Sun can be absorbed by the electrons in the xenon atoms via the axion-electron coupling. Meanwhile, they can also scatter with the atoms through the inverse Primakoff process via the axion-photon coupling, which emits a photon and mimics the electronic recoil signals. We found that the latter process cannot be neglected. After including the keV photon produced via the inverse Primakoff process in the detection, the tension with the astrophysical constraints can be significantly reduced. We also explore scenarios involving additional new physics to further alleviate the tension with the astrophysical bounds.

Harnessing nanomedicine to overcome the immunosuppressive tumor microenvironment.

Cancer immunotherapy has received extensive attention due to its ability to activate the innate or adaptive immune systems of patients to combat tumors. Despite a few clinical successes, further endeavors are still needed to tackle unresolved issues, including limited response rates, development of resistance, and immune-related toxicities. Accumulating evidence has pinpointed the tumor microenvironment (TME) as one of the major obstacles in cancer immunotherapy due to its detrimental impacts on tumor-infiltrating immune cells. Nanomedicine has been battling with the TME in the past several decades, and the experience obtained could be exploited to improve current paradigms of immunotherapy. Here, we discuss the metabolic features of the TME and its influence on different types of immune cells. The recent progress in nanoenabled cancer immunotherapy has been summarized with a highlight on the modulation of immune cells, tumor stroma, cytokines and enzymes to reverse the immunosuppressive TME.

The Cys2His2 zinc finger protein Zfp1 regulates sexual reproduction and virulence in Cryptococcus neoformans.

Cryptococcus neoformans is a ubiquitous yeast pathogen that often infects the human central nervous system (CNS) to cause meningitis in immunocompromised individuals. Although numerous signaling pathways and factors important for fungal sexual reproduction and virulence have been investigated, their precise mechanism of action remains to be further elucidated. In this study, we identified and characterized a novel zinc finger protein Zfp1 that regulates fungal sexual reproduction and virulence in C. neoformans. qRT-PCR and ZFP1 promoter regulatory activity assays revealed a ubiquitous expression pattern of ZFP1 in all stages during mating. Subcellular localization analysis indicates that Zfp1 is targeted to the cytoplasm of C. neoformans. In vitro assays of stress responses showed that zfp1Δ mutants and the ZFP1 overexpressed strains ZFP1OE are hypersensitive to SDS, but not Congo red, indicating that Zfp1 may regulate cell membrane integrity. Zfp1 is also essential for fungal sexual reproduction because basidiospore production was blocked in bilateral mating between zfp1Δ mutants or ZFP1 overexpressed strains. Fungal nuclei development assay showed that nuclei in the bilateral mating of zfp1Δ mutants or ZFP1 overexpressed strains failed to undergo meiosis after fusion, indicating Zfp1 is important for regulating meiosis during mating. Although zfp1Δ mutants showed normal growth and produced normal major virulence factors, virulence was attenuated in a murine model. Interestingly, we found that the ZFP1 overexpressed strains were avirulent in a murine systemic-infection model. Overall, our study showed that the zinc finger protein Zfp1 is essential for fungal sporulation and virulence in C. neoformans.

Enhancing Long-Lived Particles Searches at the LHC with Precision Timing Information.

We explore the physics potential of using precision timing information at the LHC in searches for long-lived particles (LLPs). In comparison with the light standard model particles, the decay products of massive LLPs arrive at detectors with time delays around the nanosecond scale. We propose new strategies to take advantage of this time delay feature by using initial state radiation to time stamp the collision event and require at least one LLP to decay within the detector. This search strategy is effective for a broad range of models. In addition to outlining this general approach, we demonstrate its effectiveness with the projected reach for two benchmark scenarios: a Higgs boson decaying into a pair of LLPs, and pair production of long-lived neutralinos in the gauge mediated supersymmetry breaking models. Our strategy increases the sensitivity to the lifetime of the LLP by two orders of magnitude or more and particularly exhibits a better behavior with a linear dependence on the lifetime in the large lifetime region compared to traditional LLP searches. The timing information significantly reduces the standard model background and provides a powerful new dimension for LLP searches.

Opening Up the Compressed Region of Top Squark Searches at 13 TeV LHC.

Light top superpartners play a key role in stabilizing the electroweak scale in supersymmetric theories. For R-parity conserved supersymmetric models, traditional searches are not sensitive to the compressed regions. In this Letter, we propose a new method targeting this region, with top squark and neutralino mass splitting ranging from m_{t[over ˜]}-m_{χ}≳m_{t} to about 20 GeV. In particular, we focus on the signal process in which a pair of top squarks are produced in association with a hard jet, and we define a new observable R_{M} whose distribution has a peak in this compressed region. The position of the peak is closely correlated with m_{t[over ˜]}. We show that for the 13 TeV LHC with a luminosity of 3000 fb^{-1}, this analysis can extend the reach of the top squark in the compressed region to m_{t[over ˜]} around 800 GeV.

Curcumin induces apoptosis through mitochondrial pathway and caspases activation in human melanoma cells.

Melanoma is the most malignant skin cancer and is highly resistant to chemotherapy and radiotherapy. Curcumin is a component of turmeric, the yellow spice derived from the rhizome of Curcuma longa. It has been demonstrated to modulate multiple cell signaling pathways, including apoptosis, proliferation, angiogenesis and inflammation. In this study, we studied the signaling pathways involved in melanoma cell death after treatment with curcumin using western blotting. Colorimetric assays (MTT) assessed cell viability. Flow cytometry and DNA laddering evaluated cell apoptosis. Fluorescent microscopy was used to evaluate of Hoechst 33342 staining of nuclei. The result demonstrated that curcumin could induce apoptosis and inhibit proliferation in melanoma cells. Curcumin stimulated the expression of pro-apoptotic Bax, and inhibited the activation of anti-apoptotic Mcl-1 and Bcl-2. During curcumin treatment, caspase-8 and Caspase-3 were cleaved in time and dose-dependent manners. Curcumin treatment also altered the expressions of apoptosis associated proteins NF-κB, p38 and p53. Curcumin induced DNA double strand breaks, which were indicated by phosphorylated H2AX. Our data suggested that curcumin could be used as a novel and effective approach for the treatment of melanoma.

Rap2B promotes migration and invasion of human suprarenal epithelioma.

The aim of our study was to elucidate the role of Rap2B in the development of human suprarenal epithelioma and to investigate the effect of Rap2B on suprarenal epithelioma cells migration and invasion. We use tissue microarray and immunohistochemistry to evaluate Rap2B staining in 75 suprarenal epithelioma tissues and 75 tumor-adjacent normal renal tissues. And the expression of Rap2B protein in human suprarenal epithelioma cells and tissues was detected by western blot simultaneously. The role of Rap2B in suprarenal epithelioma cells migration and invasion was detected by using wound healing assay, cell migration assay, and matrigel invasion assay. After that, we performed western blot analysis and gelatin zymography to detect MMP-2 protein expression and enzyme activity. Our research showed that Rap2B expression was increased in tumor tissues compared with tumor-adjacent normal renal tissues. But no correlation was found between Rap2B expression and clinicopathological parameters. In addition, we found that Rap2B promoted the cell migration and invasion abilities, and Rap2B increased MMP-2 expression and enzyme activity in suprarenal epithelioma cells. Our data indicated that Rap2B expression is significantly increased in human suprarenal epithelioma and Rap2B can promote the cell migration and invasion abilities, which may provide a new target for the treatment of suprarenal epithelioma.

Supersymmetric exotic decays of the 125 GeV Higgs boson.

We reveal a set of novel decay topologies for the 125 GeV Higgs boson in supersymmetry which are initiated by its decay into a pair of neutralinos, and discuss their collider search strategies. This category of exotic Higgs decays is characterized by the collider signature: visible objects+E_{T}, with E_{T} dominantly arising from escaping dark matter particles. Their benchmark arises naturally in the Peccei-Quinn symmetry limit of the minimal supersymmetric standard model singlet extensions, which is typified by the coexistence of three light particles: singletlike scalar h_{1} and pseudoscalar a_{1}, and singlinolike neutralino χ_{1}, all with masses of ≲10 GeV, and the generic suppression of the exotic decays of the 125 GeV Higgs boson h_{2}→h_{1}h_{1}, a_{1}a_{1} and χ_{1}χ_{1}, however. As an illustration, we study the decay topology: h_{2}→χ_{1}χ_{2}, where the binolike χ_{2} decays to h_{1}χ_{1} or a_{1}χ_{1}, and h_{1}/a_{1}→ff[over ¯], with ff[over ¯]=µ^{+}µ^{-}, bb[over ¯]. In the dimuon case (m_{h_{1}/a_{1}}∼1 GeV), a statistical sensitivity of S/sqrt[B]>6σ can be achieved easily at the 8 TeV LHC, assuming σ(pp→Wh_{2})/σ(pp→Wh_{SM})Br(h_{2}→µ^{+}µ^{-}χ_{1}χ_{1})=0.1. In the bb[over ¯] case (m_{h_{1}/a_{1}}∼45 GeV), 600 fb^{-1} data at the 14 TeV LHC can lead to a statistical sensitivity of S/sqrt[B]>5σ, assuming σ(pp→Zh_{2})/σ(pp→Zh_{SM})Br(h_{2}→bb[over ¯]χ_{1}χ_{1})=0.5. These exotic decays open a new avenue for exploring new physics couplings with the 125 GeV Higgs boson at colliders.

Progression of O6-methylguanine-DNA methyltransferase and temozolomide resistance in cancer research.

Temozolomide (TMZ) is an alkylating agent that is widely used in chemotherapy for cancer. A key mechanism of resistance to TMZ is the overexpression of O(6)-methylguanine-DNA methyltransferase (MGMT). MGMT specifically repairs the DNA O(6)-methylation damage induced by TMZ and irreversibly inactivates TMZ. Regulation of MGMT expression and research regarding the mechanism of TMZ resistance will help rationalize the clinical use of TMZ. In this review, we provide an overview of recent advances in the field, with particular emphasis on MGMT structure, function, expression regulation, and the association between MGMT and resistance to TMZ.

Iron-carbon dots embedded in molybdenum single-atom nanoflowers as multifunctional nanozyme for dual-mode detection of hydrogen peroxide and uric acid.

Single-atom catalysts (SACs) have attracted extensive attention in the field of catalysis due to their excellent catalytic ability and enhanced atomic utilization, but the multi-mode single-atom nanozymes for biosensors remain a challenging issue. In this work, iron-doped carbon dots (Fe CDs) were loaded onto the edges and pores of Mo SACs with nanoflower morphology; accordingly, a composite material Fe CDs/Mo SACs was prepared successfully, which improves the catalytic performance and develops a fluorescence mode without changing the original morphology. The steady-state kinetic data indicates that the material prepared have better affinity for substrates and faster reaction rates under optimized conditions. The specific kinetic parameters Km and Vmax were calculated as 0.39 mM and 7.502×10-7 M·s-1 respectively. The excellent peroxidase-like activity of Fe CDs/Mo SACs allows H2O2 to decompose into •OH, which in turn oxidizes colorless o-phenylenediamine (OPD) to yellow 2,3-diaminophenazine (DAP). At the same time, the fluorescence signal of Fe CDs/Mo SACs quenches obviously by DAP at 460 nm through internal filtration effect (IFE), while the characteristic fluorescence response of DAP gradually increases at 590 nm. Based on this sensing mechanism, a sensitive and accurate dual-mode (colorimetric and ratiometric fluorescent) sensor was constructed to detect H2O2 and uric acid, and the rate of recovery and linearity were acceptable for the detection of UA in human serum and urine samples. This method provides a new strategy for rapid and sensitive detection of UA, and also broadens the development of SACs in the field of biosensors.

A dual-regulated oncolytic adenovirus expressing interleukin-24 sensitizes melanoma cells to temozolomide via the induction of apoptosis.

Malignant melanoma is one of the most lethal and aggressive human malignancies. Suppressed apoptosis and extraordinary invasiveness are the distinctive features that contribute to malignant melanoma. The alkylating agent temozolomide (TMZ) is one of the most effective single chemotherapeutic agents for patients with malignant melanoma, but resistance develops quickly and with high frequency. We constructed a dual-regulated oncolytic adenovirus expressing interleukin 24 (IL-24) gene (Ki67-ZD55-IL-24) by utilizing the Ki67 promoter to replace the native viral promoter of E1A gene. We investigated whether a combination of Ki67-ZD55-IL-24-mediated gene virotherapy and chemotherapy using TMZ produces increased cytotoxicity against human melanoma cells via the induction of apoptosis. Our data indicate that this novel strategy thus holds promising potentials for further developing an effective approach to treat malignant melanoma.

Ratiometric colorimetric detection of nitrite using CoMnO3 nanofibers as an oxidase-like enzyme to induce diazotization reaction.

Nitrite is a typical food additive and preservative used in the food industry, which has attracted considerable attention due to its severe adverse effects on human health. Herein, a sensitive and highly selective ratiometric colorimetric sensing platform for the detection of nitrite was created based on a polymetallic oxide nanozyme, CoMnO3 nanofibers (CMO) catalysis integrated with the particular diazotization reaction. The nanozyme has superior oxidase-like activity (Km was 0.105 mM and Vmax was 63.7 × 10-8 M S-1) and could catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) to oxidized TMB (oxTMB), as CMO could achieve the conversion of oxygen in the solution to superoxide anion (O2˙-). In addition, it is interesting to note that oxTMB can be diazotized in the presence of nitrite under acidic conditions, causing a shift in the ratio of nitrite concentration to the absorbance peaks at 450 and 652 nm (A450/A652). The ratio of A450/A652 exhibited a positive linear relationship with the concentration of nitrite within the concentration range of 0.2-200 µM, with a detection limit of 0.094 µM. Simultaneously, this method was also successful in quantifying the nitrite produced by brined and pickled foods and the dynamic tracking of the nitrite levels in various types of dishes. The analysis method not only offers dual-signal ratio sensing with high sensitivity but also holds the benefit of outstanding selectivity for the use of the particular reaction, which has a wide range of application prospects in food safety management.

Enhancing catalytic performance of Fe and Mo co-doped dual single-atom catalysts with dual-enzyme activities for sensitive detection of hydrogen peroxide and uric acid.

Single-atom catalysts (SACs) have attracted much attention due to their excellent catalytic activity, but the improvement of atomic loading which means that weight fraction (wt%) of metal atom was still facing great challenges. In this work, iron and molybdenum co-doped dual single-atom catalysts (Fe/Mo DSACs) was prepared for the first time by using the soft template sacrifice strategy, which improved significantly the atomic load and exhibited both the oxidase-like (OXD) activity and the dominant peroxidase-like (POD) activity. Further experiments reveal that Fe/Mo DSACs can not only catalyze O2 to generate O2•- and 1O2, but also catalyze H2O2 to generate a large number of •OH, which caused 3, 3', 5, 5'-tetramethylbenzidine (TMB) to be oxidized to oxTMB, accompanied by the color changing from colorless to blue. The steady-state kinetic test showed that Michaelis-Menten constant (Km) values and the maximum initial velocity values (Vmax) of the POD activity of Fe/Mo DSACs were 0.0018 mM and 12.6 × 10-8 M s-1, respectively. The corresponding catalytic efficiency was tens of times higher than Fe SACs and Mo SACs, which proves that the synergistic effect between Fe and Mo has significantly improved the catalytic ability. Based on the excellent POD activity of Fe/Mo DSACs, a colorimetric sensing platform combined with TMB was proposed to realize the sensitive detection of H2O2 and uric acid (UA) in a wide range, with limits of detection as low as 0.13 and 0.18 µM, respectively. Finally, accurate and reliable results were obtained in the detection of H2O2 in cells, and of UA in human serum and urine.