Based on the analytical framework of the cumulative advantage theory, this article investigates how the urban status of signing auditors affects audit quality and the channels behind it. Using listed companies in Shanghai and Shenzhen Exchanges, the research finds that signing auditors' urban status significantly enhances audit quality, whereas auditor industry specialization mitigates this effect. The conclusions hold validity across a series of robustness tests, including substitutions of dependent and independent variables, 2SLS regression, firm fixed effects, and placebo test. Channel tests reveal that higher education and partner status serve as key pathways through which signing auditors' urban status influences audit quality. The findings broaden the scope of influence of the hukou system and provide a fresh perspective for understanding how individual auditor characteristics affect audit behavior within the context of China's institutional framework.

For the 3-D quadratic quasilinear wave equations in exterior domains with Dirichlet or Neumann boundary conditions, the global existence or the maximal existence time of small data smooth solutions have been established in the past. However, so far it is still open for the corresponding 2-D Neumann boundary value problem. In this paper, we investigate the long time existence of small data solutions to 2-D quadratic quasilinear wave equations with homogeneous Neumann boundary values. Our main ingredients include: establishing some new pointwise spacetime decay estimates for the 2-D initial boundary value problem of the divergence form wave equations, and introducing a series of good unknowns to derive the required energy estimates. The obtained results can be directly applied to the initial boundary value problem of 2-D isentropic and irrotational compressible Euler equations for both the polytropic gases and the Chaplygin gases in exterior domains with impermeable conditions, the 2-D relativistic membrane equations and 2-D membrane equations with homogeneous Neumann boundary values.

BackgroundDrug resistance, characterized by high heterogeneity and complex mechanisms, poses a significant challenge in cancer treatment. Stratifying resistant tumors into biologically and clinically meaningful subgroups can improve prognostic evaluation and help guide treatment decisions. However, the DNA methylation-based subtypes of resistant tumors have not yet been comprehensively characterized.ResultsDNA methylation profiles from resistant tumors were retrieved from public database including TCGA and GEO. For each tumor type resistant to a specific treatment drug, consensus clustering based on the most variable methylated probes was conducted to identify the DNA methylation subtypes of resistant tumors. For low-grade glioma (LGG) resistant to Temozolomide, consensus clustering of highly variable CpGs identified two subtypes: cancer resistance CpG island methylator phenotype-positive (CR_CIMP+) and -negative (CR_CIMP-). The CR_CIMP- subtype associates with poorer prognosis, reduced drug response, and more advanced histology, exhibiting higher tumor mutation burden and greater activity in drug resistance-related pathways, such as PI3K/AKT/mTOR signaling. CR_CIMP subtypes with distinct clinical or molecular features were also identified in pancreatic adenocarcinoma and bladder urothelial carcinoma resistant to Gemcitabine, as well as in non-small cell lung cancer resistant to anti-PD1/PD-L1 immunotherapy. Based on predicted drug responses, the study screens candidate drugs for each CR_CIMP subtype. Finally, a random forest model is proposed to predict CR_CIMP subtypes in LGG patients resistant to Temozolomide.ConclusionsThis study uncovers DNA methylation subtypes within resistant tumors, enabling more precise stratification to inform prognosis and therapy selection.

This article investigates whether signing auditors' early-life famine experience affects audit quality. We rely on a sample of Chinese listed firms and show that signing auditors who have experienced great famine experience during their early life are more likely to issue modified audit opinions, indicating that these signing auditors can effectively enhance audit quality. Further, our results remain unchanged after conducting a series of sensitivity tests using alternative measures of signing auditors' early-life famine experience and audit quality, adopting PSM method, two-stage Heckman method, and placebo tests. Moreover, firms with these signing auditors have high quality financial information, and these signing auditors have more audit input with high audit fees and more audit efforts. Additionally, this study also demonstrates that the positive impact generated by these signing auditors on the quality of audit services is stronger in subsamples with high client importance. Signing auditors' later experience (major and professional experience) plays a mitigating role in the association between signing auditors' early-life famine experience and quality of audits. Our findings also reveal that signing auditors who are born in urban areas attenuate the positive impact of between signing auditors' early-life famine experience on quality of audits.

In this paper, we are concerned with the global existence and scattering of small data smooth solutions to a class of quasilinear wave systems on the product space R2 & times; T. These quasilinear wave systems include 3-D irrotational potential flow equation of Chaplygin gases, 3-D relativistic membrane equation, some 3-D quasilinear wave equations which come from the corresponding Lagrangian functionals as perturbations of the Lagrangian densities of linear wave operators, and 3-D nonlinear wave maps system. Through looking for some new transformations of unknown functions, the nonlinear wave system can be reduced into a more tractable form. Subsequently, by applying the vector-field method together with the ghost weight technique as well as deriving some crucial weighted L infinity-L infinity and L infinity-L2 estimates, the global existence and scattering of small data solutions are eventually established. (c) 2026 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

It has been known that if the initial data decay sufficiently fast at space infinity, then 1D Klein-Gordon equations with quadratic nonlinearity admit classical solutions up to time e^C/ε^2 while e^C/ε^2 is also the upper bound of the lifespan, where C>0 is some suitable constant and ε>0 is the size of the initial data. In this paper, we will focus on the 1D nonlinear Klein-Gordon equations with weakly decaying initial data. It is shown that if the H^s-Sobolev norm with (1+|x|)^1/2+ weight of the initial data is small, then the almost global solutions exist; if the initial H^s-Sobolev norm with (1+|x|)^1/2 weight is small, then for any M>0, the solutions exist on [0,ε^-M]. Our proof is based on the dispersive estimate with a suitable Z-norm and a delicate analysis on the phase function.

It is well known that for the quasilinear Klein-Gordon equation with quadratic nonlinearity and sufficiently decaying small initial data, there exists a global smooth solution if the space dimensions $d\geq2$. When the initial data are of size $\varepsilon>0$ in the Sobolev space, for the semilinear Klein-Gordon equation satisfying the null condition, the authors in the article (J.-M. Delort, Daoyuan Fang, Almost global existence for solutions of semilinear Klein-Gordon equations with small weakly decaying Cauchy data, Comm. Partial Differential Equations 25 (2000), no. 11-12, 2119--2169) prove that the solution exists in time $[0,T_\varepsilon)$ with $T_\varepsilon\ge Ce^{C\varepsilon^{-\mu}}$ ($\mu=1$ if $d\ge3$, $\mu=2/3$ if $d=2$). In the present paper, we will focus on the general quasilinear Klein-Gordon equation without the null condition and further show that the existence time of the solution can be improved to $T_\varepsilon=+\infty$ if $d\geq3$ and $T_\varepsilon\ge e^{C\varepsilon^{-2}}$ if $d=2$. In addition, for $d=2$ and any fixed number $\alpha>0$, if the weighted $L^2$ norm of the initial data with the weight $(1+|x|)^\alpha$ is small, then the solution exists globally and scatters to a free solution. The arguments are based on the introduction of a good unknown, the Strichartz estimate, the weighted $L^2$-norm estimate and the resonance analysis.

Let P, M be two primes such that (P, M) = 1. Let f be a Hecke newform of level P, and chi a primitive Dirichlet character modulo M. In this paper, we study the hybrid sub-convexity problem for L(s, sym(2)f circle times chi) simultaneously in the level and conductor aspects. Among other things, we prove that the hybrid subconvex bound can be achieved, so long as M-epsilon < P < M-3/20. One of the key ingredients is that we develop the classical level aspect version of the Voronoi formula for the symmetric square lift in an alternative way by t racing back to its geometric nature. As the direct applications, we obtained the subconvex bound for L(s, f circle times f circle times chi) simultaneously in the level and conductor aspects and the non-obvious bound for the problem of distinguishing modular forms f and f(chi) based on their first Fourier coefficients. (c) 2025 Published by Elsevier Inc.

Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by rapid proliferation and a great propensity for metastasis. Therapeutic options for TNBC remain limited due to the absence of targetable hormone receptors. While BET bromodomain inhibitors (BBDIs) exhibit promising anticancer potential, the emergence of drug resistance presents a major challenge. Here, through leveraging single-cell RNA sequencing (scRNA-seq) data across continuous states of BBDI treatment in TNBC, this study conducts an extensive investigation into BBDI resistance, and develops two computational frameworks, FR20 and D-FR20, to quantify BBDI resistance at single-cell resolution and to screen potential BBDI re-sensitizer drugs, respectively. The accuracy and scalability of FR20 are confirmed through rigorous evaluation in nine independent datasets. In addition, cellular dynamic changes and ferroptosis inhibition are revealed in the evolution of BBDI resistance. Experimental validation demonstrates that GPX4 overexpression significantly reduces drug sensitivity in TNBC cells. Furthermore, in vitro and in vivo experiments validate the ability of the small molecule filgotinib, identified by D-FR20, to re-sensitize BBDI and effectively eliminate resistant TNBC cells. Collectively, this study provides two computational frameworks for predicting BBDI resistance and candidate re-sensitizer, as well as demonstrates the roles of ferroptosis in BBDI resistance, offering a promising avenue for TNBC treatment.

In the paper [M. Keel, H. Smith, C.D. Sogge, Almost global existence for quasilinear wave equations in three space dimensions. J. Amer. Math. Soc. 17 (2004), no. 1, 109-153], the authors prove that for the 3-D quadratic quasilinear wave equation in exterior domains with homogenous Dirichlet boundary value and small initial data of size ε, the lifespan T̅_ε of the smooth solution fulfills T̅_ε≥ e^C/ε. However, for the corresponding 2-D quadratic quasilinear wave equation in exterior domains with homogenous Dirichlet or Neumann boundary value, so far it is still open whether the expected sharp lifespan T_ε≥C/ε^2 holds or not. In this paper, we will solve this open question. Our main ingredients include: introducing the suitable Friedlander radiation field for the 2-D linear wave equation in exterior domains with homogenous Dirichlet or Neumann boundary value, constructing the delicate approximate solution, and establishing some crucial space-time decay estimates for the solutions of 2-D quasilinear wave equation in exterior domains. On the other hand, for the radial symmetric solutions to a class of 2-D quadratic quasilinear wave equation in exterior domains, the upper bound of the lifespan T_ε≤C/ε^2 is derived and the sharp constant C is also determined explicitly.

In this paper, we solve the global Dirichelt boundary value problem for the system of 2-D wave maps type equations with the form square u(I)= Sigma(M)(J,K,L=1) C(IJKL)u(J) Q(0)(u(K), u(L)) (1 <= I <= M) and Q(0)(f, g)= partial derivative(t) f partial derivative(t) g - Sigma(2)(j=1) partial derivative(j) f partial derivative(j) g in exterior domain. By establishing some crucial classes of pointwise spacetime decay estimates for the small data solution u=(u(1), ..., u(M)) and its derivatives, the global existence of uis shown. (c) 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

In our previous paper [Fei Hou, Fei Tao, Huicheng Yin, Global existence and scattering of small data smooth solutions to a class of quasilinear wave systems on R(2)xT, Preprint (2024), arXiv:2405.03242], for the Q(0)-type quadratic nonlinearities, we have shown the global well-posedness and scattering properties of small data smooth solutions to the quasilinear wave systems on R(2)xT . In this paper, we start to solve the global existence problem for the remaining Q(alpha beta)-type nonlinearities. By combining these results, we have established the global well-posedness of small solutions R(2)xT on for the general 3-D quadratically quasilinear wave systems when the related 2-D null conditions are fulfilled.

Esophageal cancer is one of the most prevalent malignancies. This study aimed to examine the impact of factors such as immunotherapy, altitude, radiotherapy target volume, and radiotherapy dose on the prognosis of patients with locally advanced and advanced esophageal cancer who are receiving definitive radiotherapy and living in high-altitude regions. We retrospectively collected data from all patients with locally advanced and advanced esophageal cancer who completed definitive radiotherapy at Yunnan Cancer Hospital between January 2017 and January 2023. A total of 274 patients were included, with a median follow-up time of 24.5 months. The median overall survival (OS) and progression-free survival (PFS) were 15.0 months and 11.0 months, respectively. Adjuvant therapy (including chemotherapy, immunotherapy, and antiangiogenic targeted therapy, P = 0.004) and gross target volume (GTV, P = 0.015) were independent predictors of overall survival, whereas body mass index (BMI, P = 0.037) was an independent predictor of progression-free survival. Patients with a smaller planning target volume (PTV), clinical target volume (CTV), GTV, and gross tumor volume of metastatic regional lymph nodes (GTVnd), as well as those with a smaller New target volume, had a better prognosis. Treatment efficacy affects patient prognosis, with those showing early therapeutic effectiveness having a better prognosis than those for whom the treatment is ineffective. Patients who experienced disease progression within three months after the end of radiotherapy had a poorer prognosis. The altitude and radiotherapy dose had no significant impact on the prognosis of esophageal cancer patients. The location of the lesion, GTV, and simultaneous integrated boost (SIB) radiotherapy were factors influencing the occurrence of esophageal fistulas.

Let $F$ be a self-dual Hecke-Maaß form for ${\rm{GL}}(3)$ underlying the symmetric square lift of a ${\rm{GL}}(2)$-newform of square-free level and trivial nebentypus. In this paper, we are interested in the first moments of the central values of ${\rm{GL}}(3) \times {\rm{GL}}(2)$ $L$-functions and ${\rm{GL}}(2)$ $L$-functions. As a result, we obtain an estimate for the first moment for $L(1/2, F\otimes f)$ over a family, where $F$ is of the level $q^2$, and $f\in \mathcal{B}^\ast_k(M)$ for any primes $q,M\ge 2$ such that $(q,M)=1$. We prove the subconvex bound for $L(1/2, F\otimes f)$ involving the levels aspects simultaneously in the range $M^{13/64+\varepsilon }\le q \le M^{11/40-\varepsilon}$ and $M> q^\delta$ for any $\varepsilon, \delta>0$ for the first time. Moreover, we further investigate the first moments of these $L$-functions in the weight $k$ aspect over $K\le k\le 2K$, with $K$ being a large number. As the results, we obtain a Lindelöf average bound for the first moment of $L(1/2, f)L(1/2, F\otimes f)$ of degree 8 and an asymptotic formula for the first moment of $L(1/2, F\otimes f)$ with an error term of $O(K^{-1/4+\varepsilon})$, respectively.

In the paper [S. Alinhac, The null condition for quasilinear wave equations in two space dimensions I, Invent. Math. 145 (2001), no. 3, 597-618], S. Alinhac established the global existence of small data smooth solutions to the Cauchy problem of 2-D quadratically quasilinear wave equations with null conditions. However, for the corresponding 2-D initial boundary value problem in exterior domains, it is still open whether the global solutions exist. When the 2-D quadratic nonlinearity admits a special Q_0 type null form, the global small solution is shown in our previous article [Hou Fei, Yin Huicheng, Yuan Meng, Global smooth solutions of 2-D quadratically quasilinear wave equations with null conditions in exterior domains, arXiv:2411.06984]. In the present paper, we now solve this open problem through proving the global existence of small solutions to 2-D general quasilinear wave equations with null conditions in exterior domains. Our proof procedure is based on finding appropriate divergence structures of quasilinear wave equations under null conditions, introducing a good unknown to eliminate the resulting Q_0 type nonlinearity and deriving some new precise pointwise spacetime decay estimates of solutions and their derivatives.

Piezo channels are currently known to be the most sensitive molecular mechanoreceptors. Piezo can respond to membrane tension, sag, shear force, tensile and other mechanical stimuli, produces fast inactivation, small conductance, and low threshold current. In eukaryotic cells, Piezo has two family members: Piezo1 and Piezo2. Functionally, Piezo1 detects whole-membrane tension changes, including swelling and compression. Piezo2 is more likely to sense specific mechanical stimuli, including touch and airway stretching. In the ocular system, Piezo1 and Piezo2 are expressed across various cells and tissues. This article provides a comprehensive review of the expression, distribution, and function of Piezo channels in ocular tissues, offering novel insights for the treatment of eye diseases.

This paper explores the effect of signing auditors' red origin on audit quality. Using a sample of Chinese listed firms, we show that signing auditors with red cultural background are negatively associated with earnings management, indicating that these signing auditors are capable to provide high audit quality. In addition, we find that firms who are audited by signing auditors with red cultural background have high likelihood to receive modified audit opinion, lower likelihood of financial statements and small profit. Further, empirical results show the education level of signing auditors mitigates the above relationship. After applying propensity score matching approach, Heckman two-stage method, and placebo tests, our results still stand.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, yet the response rate remains limited, with only about 30% of solid tumor patients benefiting. Identifying reliable biomarkers to predict ICIs response remains a significant challenge. In this study, we proposed a refined Hallmark gene set-based Approach for Predicting Immunotherapy Response (HAPIR). Through comprehensive multi-cohort analyses encompassing six TIGER cohorts (n = 352) and TCGA-SKCM (n = 472), we validated the optimal performance of HAPIR. Using transcriptomic data from a training cohort, we firstly refined seven Hallmark gene sets enriched with differentially expressed genes between responder and non-responder patients. Then, a logistic regression model trained based on the activities of these gene sets demonstrated superior predictive performance (AUROC = 0.778) in ten-fold cross-validation, significantly outperforming 13 existing biomarkers, including PD-1 (AUROC = 0.678) and PD-L1 (AUROC = 0.54). HAPIR’s robustness was further validated in the validation set and four independent cohorts spanning multiple cancer types (melanoma, NSCLC, and STAD), consistently achieving average AUROC = 0.745. Beyond well-known biomarkers, HAPIR surpassed both gene-based and alternative gene set-based models. Importantly, HAPIR scores correlated significantly with patient survival and effectively recapitulated the immune microenvironment, enabling the prediction of potential drug targets and drug candidates to overcome immunotherapy resistance. In conclusion, HAPIR is a promising tool for predicting ICIs response and guiding the development of new immunotherapy strategies.

In this paper, we investigate the structures of certain triple product L-functions in the level aspect, and explicitly compute the exact quotients between them and the associated Dirichlet series, where, for the latter, the fundamental pre-condition of the suitable functional equations as assumed in the previous work of Friedlander-Iwaniec [Summation formulae for coefficients of L-functions, Canad. J. Math. 57 (2005) 494-505] will not be satisfied any more. As a result, we study the average behavior of the coefficients of these Dirichlet series, by establishing the power-saving estimates for the sums of them with the level parameters explicitly determined, and obtain the quantitative estimates for nonlinear exponential sums involving the Rankin-Selberg L-functions corresponding to the configurations GL2 xGL4 and GL3 xGL4.

Patients have a limited response rate to immune checkpoint inhibitors (ICIs) therapy. Although several biomarkers have been proposed, their ability to accurately predict the response to ICIs therapy remains unsatisfactory. In addition, mutational signatures were validated to be associated with ICIs therapy. Therefore, we developed a mutational signature-based biomarker (MS-bio) to predict the response to ICIs therapy. Based on differentially mutated genes, we extracted six mutational signatures (single-base substitution (SBS)-A, SBS-B, SBS-C, SBS-D, double-base substitution (DBS)-A, and DBS-B) as MS-bio, and constructed a random forest (RF) model to predict the response. Internal and external validations consistently demonstrated the excellent predictive capability of MS-bio, with an accuracy reaching up to 0.82. Moreover, MS-bio exhibited superior performance compared to existing biomarkers. To further validate the accuracy of MS-bio, we explored its performance in The Cancer Genome Atlas (TCGA) cohort and found that the predicted responders were immunologically "hot". Finally, we found that SBS-C had the highest importance in prediction and was related to T cell differentiation. Overall, here we introduced MS-bio as a novel biomarker for accurately predicting the response to ICIs therapy, thereby contributing to the advancement of precision medicine.