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Psychological health problems, especially emotional disorders, are common among adolescents. The epidemiology of emotional disorders is greatly influenced by stressful events. This study sought to assess the prevalence rate and socio-demographic correlates of depressive and anxiety symptoms among Chinese adolescents affected by the outbreak of COVID-19. We conducted a cross-sectional study among Chinese students aged 12–18 years during the COVID-19 epidemic period. An online survey was used to conduct rapid assessment. A total of 8079 participants were involved in the study. An online survey was used to collect demographic data, assess students’ awareness of COVID-19, and assess depressive and anxiety symptoms with the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder (GAD-7) questionnaire, respectively. The prevalence of depressive symptoms, anxiety symptoms, and a combination of depressive and anxiety symptoms was 43.7%, 37.4%, and 31.3%, respectively, among Chinese high school students during the COVID-19 outbreak. Multivariable logistic regression analysis revealed that female gender was the higher risk factor for depressive and anxiety symptoms. In terms of grades, senior high school was a risk factor for depressive and anxiety symptoms; the higher the grade, the greater the prevalence of depressive and anxiety symptoms. Our findings show there is a high prevalence of psychological health problems among adolescents, which are negatively associated with the level of awareness of COVID-19. These findings suggest that the government needs to pay more attention to psychological health among adolescents while combating COVID-19.

Background Acidity is a hallmark of malignant tumor, representing a very efficient mechanism of chemoresistance. Proton pump inhibitors (PPI) at high dosage have been shown to sensitize chemoresistant human tumor cells and tumors to cytotoxic molecules. The aim of this pilot study was to investigate the efficacy of PPI in improving the clinical outcome of docetaxel + cisplatin regimen in patients with metastatic breast cancer (MBC). Methods Patients enrolled were randomly assigned to three arms: Arm A, docetaxel 75 mg/m 2 followed by cisplatin 75 mg/m 2 on d4, repeated every 21 days with a maximum of 6 cycles; Arm B, the same chemotherapy preceded by three days esomeprazole (ESOM) 80 mg p.o. bid, beginning on d1 repeated weekly. Weekly intermittent administration of ESOM (3 days on 4 days off) was maintained up to maximum 66 weeks; Arm C, the same as Arm B with the only difference being dose of ESOM at 100 mg p.o. bid. The primary endpoint was response rate. Results Ninety-four patients were randomly assigned and underwent at least one injection of chemotherapy. Response rates for arm A, B and C were 46.9, 71.0, and 64.5 %, respectively. Median TTP for arm A ( n  = 32), B ( n  = 31), C ( n  = 31) were 8.7, 9.4, and 9.7 months, respectively. A significant difference was observed between patients who had taken PPI and who not with ORR (67.7 % vs. 46.9 %, p = 0.049) and median TTP (9.7 months vs. 8.7 months, p  = 0.045). Exploratory analysis showed that among 15 patients with triple negative breast cancer (TNBC), this difference was bigger with median TTP of 10.7 and 5.8 months, respectively ( p  = 0.011). PPI combination showed a marked effect on OS as well, while with a borderline significance (29.9 vs. 19.2 months, p  = 0.090). No additional toxicity was observed with PPI. Conclusions The results of this pilot clinical trial showed that intermittent high dose PPI enhance the antitumor effects of chemotherapy in MBC patients without evidence of additional toxicity, which requires urgent validation in a multicenter, randomized, phase III trial. Trial registration Clinicaltrials.gov identifier: NCT01069081 .

A bstract Combining the Higgs searches at the LHC, we study the Higgs inflation in the type-I and type-II two-Higgs-doublet models with non-minimally couplings to gravity. After imposing relevant theoretical and experimental constraints, we find that the Higgs inflation imposes stringent constraints on the mass splitting between A , H ± , and H , and they tend to be nearly degenerate in mass with increasing of their masses. The direct searches for Higgs at the LHC can exclude many points achieving Higgs inflation in the region of m H ( m A ) < 450 GeV in the type-I model, and impose a lower bound on tan β for the type-II model. The Higgs inflation disfavors the wrong sign Yukawa coupling region of type-II model. In the parameter space achieving the Higgs inflation, the type-I and type-II models can produce a first order electroweak phase transition, but v c / T c is much smaller than 1.0.

Topological insulators are materials that behave as insulators in the bulk and as conductors at the edge or surface due to the particular configuration of their bulk band dispersion. However, up to date possible practical applications of this band topology on materials’ bulk properties have remained abstract. Here, we propose and experimentally demonstrate a topological bulk laser. We pattern semiconductor nanodisk arrays to form a photonic crystal cavity showing topological band inversion between its interior and cladding area. In-plane light waves are reflected at topological edges forming an effective cavity feedback for lasing. This band-inversion-induced reflection mechanism induces single-mode lasing with directional vertical emission. Our topological bulk laser works at room temperature and reaches the practical requirements in terms of cavity size, threshold, linewidth, side-mode suppression ratio and directionality for most practical applications according to Institute of Electrical and Electronics Engineers and other industry standards. We believe this bulk topological effect will have applications in near-field spectroscopy, solid-state lighting, free-space optical sensing and communication.The interface between photonic crystals with distinct in-band topologies confines electromagnetic modes and gives rise to lasing emission in the bulk.

Last few decades, several economic uncertainty challenges have emerged in the energy market. This study newly contributes to existing research by inspecting the asymmetric effect of economic policy uncertainty and financial development on renewable energy consumption in China. We employ a nonlinear ARDL approach by using a time-series dataset spanning from 1990 to 2019. Our symmetric model shows that economic policy uncertainty matters in the short run, as it increases renewable energy consumption while exhibiting a negative impact on renewable energy in long run in China. Our asymmetric results in the short and long run have deviated from the symmetric results. Our asymmetric results of the short and long run are similar in direction but different in magnitude. The results show that positive change in economic policy uncertainty has increased 3.216% and negative change in economic policy uncertainty has decreased 1.461% in renewable energy consumption in long run in China. Financial development does not matter in renewable energy consumption in China. Based on these outcomes, we can draw some robust economic policies in China as well as for other pollutant economies. Policymakers should be made economic policies more predictable in the modern era.

A signaling pathway in eukaryotes known as cGAS–STING recognizes the presence of cytosolic DNA, which alerts the immune system to viral infection or cellular damage. However, the majority of DNA viruses direct their genomic DNA into nuclei, suggesting that nuclear-specific sensing is also needed. L. Wang et al. find that during herpes simplex virus–1 infection, heterogeneous nuclear ribonucleoprotein A2B1 forms a complex with viral DNA, homodimerizes, and is demethylated. These events result in translocation of the complex to the cytosol and activation of the immune system through type I interferon signaling. Additionally, the complex promotes N 6 -methyladenosine modification and translocation of cGAS–STING–related mRNAs after DNA virus infection, further amplifying the immune response. Science , this issue p. eaav0758 A DNA virus sensor in the nucleus orchestrates antiviral immune responses. DNA viruses typically eject genomic DNA into the nuclei of host cells after entry. It is unclear, however, how nuclear pathogen–derived DNA triggers innate immune responses. We report that heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) recognizes pathogenic DNA and amplifies interferon-α/β (IFN-α/β) production. Upon DNA virus infection, nuclear-localized hnRNPA2B1 senses viral DNA, homodimerizes, and is then demethylated at arginine-226 by the arginine demethylase JMJD6. This results in hnRNPA2B1 translocation to the cytoplasm where it activates the TANK-binding kinase 1–interferon regulatory factor 3 (TBK1–IRF3) pathway, leading to IFN-α/β production. Additionally, hnRNPA2B1 facilitates N 6 -methyladenosine (m 6 A) modification and nucleocytoplasmic trafficking of CGAS , IFI16 , and STING messenger RNAs. This, in turn, amplifies the activation of cytoplasmic TBK1–IRF3 mediated by these factors. Thus, hnRNPA2B1 plays important roles in initiating IFN-α/β production and enhancing stimulator of interferon genes (STING)–dependent cytoplasmic antiviral signaling.

Retinal ischemia-reperfusion (IR) injury causes irreversible loss of neurons and ultimately leads to permanent visual impairment and blindness. The cellular response under this pathological retinal condition is less clear. Using genetically modified mice, we systematically examined the behavior of microglia/macrophages after injury. We show that IR leads to activation of microglia/macrophages indicated by migration and proliferation of resident microglia and recruitment of circulating monocytes. IR-induced microglia/macrophages associate with apoptotic retinal neurons. Very interestingly, neuron loss can be mitigated by minocycline treatment. Minocycline induces Il4 expression and M2 polarization of microglia/macrophages. IL4 neutralization dampens minocycline-induced M2 polarization and neuroprotection. Given a well-established safety profile as an antibiotic, our results provide a rationale for using minocycline as a therapeutic agent for treating ischemic retinal degeneration.

A superconducting diode is an electronic device that conducts supercurrent and exhibits zero resistance primarily for one direction of applied current. Such a dissipationless diode is a desirable unit for constructing electronic circuits with ultralow power consumption. However, realizing a superconducting diode is fundamentally and technologically challenging, as it usually requires a material structure without a centre of inversion, which is scarce among superconducting materials. Here, we demonstrate a superconducting diode achieved in a conventional superconducting film patterned with a conformal array of nanoscale holes, which breaks the spatial inversion symmetry. We showcase the superconducting diode effect through switchable and reversible rectification signals, which can be three orders of magnitude larger than that from a flux-quantum diode. The introduction of conformal potential landscapes for creating a superconducting diode is thereby proven as a convenient, tunable, yet vastly advantageous tool for superconducting electronics. This could be readily applicable to any superconducting materials, including cuprates and iron-based superconductors that have higher transition temperatures and are desirable in device applications. A superconducting diode is dissipationless and desirable for electronic circuits with ultralow power consumption, yet it remains challenging to realize it. Here, the authors achieve a superconducting diode in a conventional superconducting film patterned with a conformal array of nanoscale holes.

Background The epigenetic regulation of immune response has been demonstrated in recent studies. Nonetheless, potential roles of RNA N6-methyladenosine (m 6 A) modification in tumor microenvironment (TME) cell infiltration remain unknown. Methods We comprehensively evaluated the m 6 A modification patterns of 1938 gastric cancer samples based on 21 m 6 A regulators, and systematically correlated these modification patterns with TME cell-infiltrating characteristics. The m6Ascore was constructed to quantify m 6 A modification patterns of individual tumors using principal component analysis algorithms. Results Three distinct m 6 A modification patterns were determined. The TME cell-infiltrating characteristics under these three patterns were highly consistent with the three immune phenotypes of tumors including immune-excluded, immune-inflamed and immune-desert phenotypes. We demonstrated the evaluation of m 6 A modification patterns within individual tumors could predict stages of tumor inflammation, subtypes, TME stromal activity, genetic variation, and patient prognosis. Low m6Ascore, characterized by increased mutation burden and activation of immunity, indicated an inflamed TME phenotype, with 69.4% 5-year survival. Activation of stroma and lack of effective immune infiltration were observed in the high m6Ascore subtype, indicating a non-inflamed and immune-exclusion TME phenotype, with poorer survival. Low m6Ascore was also linked to increased neoantigen load and enhanced response to anti-PD-1/L1 immunotherapy. Two immunotherapy cohorts confirmed patients with lower m6Ascore demonstrated significant therapeutic advantages and clinical benefits. Conclusions This work revealed the m 6 A modification played a nonnegligible role in formation of TME diversity and complexity. Evaluating the m 6 A modification pattern of individual tumor will contribute to enhancing our cognition of TME infiltration characterization and guiding more effective immunotherapy strategies. Graphical abstract

Dissolved organic phosphorus (DOP) has been identified as a key phosphorus source that supports primary production and microbial nitrogen (N2) fixation. However, the specific contribution and spatial distribution of DOP utilization remain poorly understood due to limited in‐situ measurements. In this study, we explored the role of DOP in supporting N2 fixation using a modified inverse biogeochemical ocean model. Our findings reveal that DOP utilization primarily occurs in subtropical gyres, where it serves as a critical phosphorus source. Direct DOP assimilation reduces phosphorus limitation in nutrient‐depleted gyres, thereby stimulating global N2 fixation, the global distribution of which is re‐estimated. The new estimate shows a significant increase in N2 fixation rates in the North Atlantic compared to the previous estimate because DOP utilization reduces the severe phosphorus limitation in that region. Neglecting DOP utilization would result in an approximately 9% underestimation of the global N2 fixation rate.