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Background: Osteosarcoma (OS), a bone tumor with high ability of invasion and metastasis, has seriously affected the health of children and adolescents. Many studies have suggested a connection between OS and the epithelial-mesenchymal transition (EMT). We aimed to integrate EMT-Related genes (EMT-RGs) to predict the prognosis, immune infiltration, and therapeutic response of patients with OS. Methods: We used consensus clustering to identify potential EMT-Related OS molecular subtypes. Somatic mutation, tumor immune microenvironment, and functional enrichment analyses were performed for each subtype. We next constructed an EMT-Related risk signature and evaluated it by Kaplan-Meier (K-M) analysis survival and receiver operating characteristic (ROC) curves. Moreover, we constructed a nomogram to more accurately predict OS patients' clinical outcomes. Response effects of immunotherapy in OS patients was analyzed by Tumor Immune Dysfunction and Exclusion (TIDE) analysis, while sensitivity for chemotherapeutic agents was analyzed using oncoPredict. Finally, the expression patterns of hub genes were investigated by single-cell RNA sequencing (scRNA-seq) data analysis. Results: A total of 53 EMT-RDGs related to prognosis were identified, separating OS samples into two separate subgroups. The EMT-high subgroup showed favourable overall survival and more active immune response. Significant correlations were found between EMT-Related DEGs and functions as well as pathways linked to the development of OS. Additionally, a risk signature was established and OS patients were divided into two categories based on the risk scores. The signature presented a good predictive performance and could be recognized as an independent predictive factor for OS. Furthermore, patients with higher risk scores exhibited better sensitivity for five drugs, while no significant difference existed in immunotherapy response between the two risk subgroups. scRNA-seq data analysis displayed different expression patterns of the hub genes. Conclusion: We developed a novel EMT-Related risk signature that can be considered as an independent predictor for OS, which may help improve clinical outcome prediction and guide personalized treatments for patients with OS.
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ABSTRACT: Pelvic fractures are severe traumatic injuries often accompanied by potentially fatal massive bleeding. Rapid control of hemorrhages in pre-hospital emergency settings is critical for improving outcomes in traumatic bleeding. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a promising technique for controlling active bleeding from pelvic fractures. By inserting a balloon catheter into the aorta, REBOA helps maintain blood flow to vital organs such as the brain and heart. This paper provides a comprehensive overview of the initial management of non-compressive trunk hemorrhage caused by pelvic fractures, introduces the technical principles and developments of REBOA, and explores its extensive application in pre-hospital emergency care. It delves into the operational details and outlines strategies for effectively managing potential complications. We aim to offer a theoretical framework for the future utilization of REBOA in managing uncontrollable hemorrhage associated with pelvic fractures in pre-hospital emergencies.
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BACKGROUND: This study was designed to develop a combined radiomics nomogram to preoperatively predict the risk categorization of thymomas based on contrast-enhanced computed tomography (CE-CT) images. MATERIALS: The clinical and CT data of 178 patients with thymoma (100 patients with low-risk thymomas and 78 patients with high-risk thymomas) collected in our hospital from March 2018 to July 2023 were retrospectively analyzed. The patients were randomly divided into a training set (n = 125) and a validation set (n = 53) in a 7:3 ratio. Qualitative radiological features were recorded, including (a) tumor diameter, (b) location, (c) shape, (d) capsule integrity, (e) calcification, (f) necrosis, (g) fatty infiltration, (h) lymphadenopathy, and (i) enhanced CT value. Radiomics features were extracted from each CE-CT volume of interest (VOI), and the least absolute shrinkage and selection operator (LASSO) algorithm was performed to select the optimal discriminative ones. A combined radiomics nomogram was further established based on the clinical factors and radiomics scores. The differentiating efficacy was determined using receiver operating characteristic (ROC) analysis. RESULTS: Only one clinical factor (incomplete capsule) and seven radiomics features were found to be independent predictors and were used to establish the radiomics nomogram. In differentiating low-risk thymomas (types A, AB, and B1) from high-risk ones (types B2 and B3), the nomogram demonstrated better diagnostic efficacy than any single model, with the respective area under the curve (AUC), accuracy, sensitivity, and specificity of 0.974, 0.921, 0.962 and 0.900 in the training cohort, 0.960, 0.892, 0923 and 0.897 in the validation cohort, respectively. The calibration curve showed good agreement between the prediction probability and actual clinical findings. CONCLUSIONS: The nomogram incorporating clinical factors and radiomics features provides additional value in differentiating the risk categorization of thymomas, which could potentially be useful in clinical practice for planning personalized treatment strategies.
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Nomogramas , Radiômica , Timoma , Neoplasias do Timo , Tomografia Computadorizada por Raios X , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Meios de Contraste , Diagnóstico Diferencial , Estudos Retrospectivos , Medição de Risco , Curva ROC , Toracotomia , Timoma/diagnóstico por imagem , Timoma/cirurgia , Neoplasias do Timo/diagnóstico por imagem , Neoplasias do Timo/cirurgia , Tomografia Computadorizada por Raios X/métodosRESUMO
Conical intersections (CIs) play a crucial role in photochemical reactions, offering an efficient channel for ultrafast non-adiabatic relaxation of excited states. This significantly influences the reaction pathways and the resulting products. In this work, we utilize the non-Markovian stochastic Schrödinger equation with complex modes method to explore the dynamics of electronic transitions through conical intersections (CIs) in pyrazine. The linear vibronic coupling model serves as the foundational framework, incorporating both intra-state and inter-state electron-vibrational interactions. The dynamics of the excited electronic transitions are analyzed across varying strengths of system-bath coupling and different bath relaxation times. The accuracy of this method is demonstrated by comparing its predictions with those from the hierarchical equations of motion method.
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Blue perovskite light-emitting diodes (PeLEDs) are crucial avenues for achieving full-color displays and lighting based on perovskite materials. However, the relatively low external quantum efficiency (EQE) has hindered their progression towards commercial applications. Quasi-two-dimensional (quasi-2D) perovskites stand out as promising candidates for blue PeLEDs, with optimized control over low-dimensional phases contributing to enhanced radiative properties of excitons. Herein, the impact of organic molecular dopants on the crystallization of various n-phase structures in quasi-2D perovskite films. The results reveal that the highly reactive bis(4-(trifluoromethyl)phenyl)phosphine oxide (BTF-PPO) molecule could effectively restrain the formation of organic spacer cation-ordered layered perovskite phases through chemical reactions, simultaneously passivate those uncoordinated Pb2+ defects. Consequently, the prepared PeLEDs exhibited a maximum EQE of 16.6 % (@ 490â nm). The finding provides a new route to design dopant molecules for phase modulation in quasi-2D PeLEDs.
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Arithmetic fluency is considered considers highly rely on language processing, encompassing essential skills. However, the independent predictive power of phonetic, semantic, or orthographic skills in relation to arithmetic fluency remains an unresolved query. This study introduces the common component hypothesis to elucidate the inconsistent findings in previous research. The hypothesis posits that significant correlations between language and mathematics hinge on whether the language and mathematics utilized in a given task share a common component. According to this hypothesis, processing skills for each of the three fundamental language elements (i.e., phonetic, semantic, orthographic) should correlate with arithmetic fluency, as these elements are also integral to simple arithmetic processing. A cohort of one hundred and ninety-eight primary school students participated in the study, undertaking a battery of tests assessing general cognitive abilities, psycholinguistic elements, and arithmetic fluency. The results showed that orthographic, phonetic, and semantic abilities independently predicted arithmetic fluency, even after accounting for all other cognitive predictors. These findings substantiate the common component hypothesis, providing empirical support for explaining the association between language and mathematics. This evidence contributes to addressing the interplay between language and mathematics in educational contexts.
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While that ROS causes DNA damage is well documented, there has been limited investigation into whether DNA damages and their repair processes can conversely induce oxidative stress. By generating a site-specific DNA double strand break (DSB) via I-SceI endonuclease expression in S. cerevisiae without damaging other cellular components, this study demonstrated that DNA repair does trigger oxidative stress. Deleting genes participating in the initiation of the resection step of homologous recombination (HR), like the MRX complex, resulted in stimulation of ROS. In contrast, deleting genes acting downstream of HR resection suppressed ROS levels. Additionally, blocking non-homologous end joining (NHEJ) also suppressed ROS. Further analysis identified Rad53 as a key player that relays DNA damage signals to alter redox metabolism in an HR-specific manner. These results suggest both HR and NHEJ can drive metabolism changes and oxidative stress, with NHEJ playing a more prominent role in ROS stimulation. Further analysis revealed a correlation between DSB-induced ROS increase and enhanced activity of NADPH oxidase Yno1 and various antioxidant enzymes. Deleting the antioxidant gene SOD1 induced synthetic lethality in HR-deficient mutants like mre11Δ and rad51Δ upon DSB induction. These findings uncover a significant interplay between DNA repair mechanisms and cellular metabolism, providing insights into understanding the side effects of genotoxic therapies and potentially aiding development of more effective cancer treatment strategies.
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Quebras de DNA de Cadeia Dupla , Reparo do DNA por Junção de Extremidades , Estresse Oxidativo , Espécies Reativas de Oxigênio , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Espécies Reativas de Oxigênio/metabolismo , Quinase do Ponto de Checagem 2/metabolismo , Quinase do Ponto de Checagem 2/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Reparo de DNA por Recombinação , Reparo do DNA , Recombinação HomólogaRESUMO
The topic of soft robotics combines robotics, biology, and material sciences to develop the next generation of robots that are better suited to complex uncertain natural environments and human-centered operations with strict safety requirements [...].
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Chemodynamic therapy (CDT) is an emerging therapeutic modality triggered by endogenous substances in the tumor microenvironment (TME) to generate reactive oxygen species. However, the mild acid pH, low H2O2 concentration, and overexpressed glutathione can suppress the CDT efficiency. Herein, ultrasound (US)-triggered Cu2+-based single-atom nanoenzymes (FA-NH2-UiO-66-Cu, FNUC) are constructed with the performance of target and glutathione depletion. In the TME, the single-atom Cu sites of FNUC consume glutathione and the FNUC:Cu+ generates â¢OH via peroxidase-like activity. The US-activated FNUC exhibits a fast â¢OH generation rate, a low Michaelis constant, and a large â¢OH concentration, indicating the cavitation effect of US promotes the â¢OH generation. Meanwhile, the tumor target of FNUC is confirmed by NIR-II fluorescence imaging, in which it is modified with IR-1061. Combined with the antitumor performance of FNUC in vitro and in vivo, the novel Cu-based SAzymes can achieve efficient and precise cancer treatment.
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Cobre , Estruturas Metalorgânicas , Microambiente Tumoral , Cobre/química , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Humanos , Animais , Microambiente Tumoral/efeitos dos fármacos , Camundongos , Catálise , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Linhagem Celular Tumoral , Glutationa/química , Ondas Ultrassônicas , Espécies Reativas de Oxigênio/metabolismoRESUMO
Currently, microbial contamination issues have globally brought out a huge health threat to human beings and animals. To be specific, microorganisms including bacteria and viruses display durable ecological toxicity and various diseases to aquatic organisms. In the past decade, the photocatalytic microorganism inactivation technique has attracted more and more concern owing to its green, low-cost, and sustainable process. A variety kinds of photocatalysts have been employed for killing microorganisms in the natural environment. However, two predominant shortcomings including low activity of photocatalysts and diverse impacts of water characteristics are still displayed in the current photocatalytic disinfection system. So far, various strategies to improve the inherent activity of photocatalysts. Other than the modification of photocatalysts, the optimization of environments of water bodies has been also conducted to enhance microorganisms inactivation. In this mini-review, we outlined the recent progress in photocatalytic sterilization of microorganisms. Meanwhile, the relevant methods of photocatalyst modification and the influences of water body characteristics on disinfection ability were thoroughly elaborated. More importantly, the relationships between strategies for constructing advanced photocatalytic microorganism inactivation systems and improved performance were correlated. Finally, the perspectives on the prospects and challenges of photocatalytic disinfection were presented. We sincerely hope that this critical mini-review can inspire some new concepts and ideas in designing advanced photocatalytic disinfection systems.
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Desinfecção , Desinfecção/métodos , Catálise , Bactérias/efeitos da radiação , Bactérias/efeitos dos fármacosRESUMO
OBJECTIVES: This study aimed to investigate the characteristics of tertiary lymphoid structures (TLSs) in oral squamous cell carcinoma (OSCC) and their association with clinical and pathological features. MATERIALS AND METHODS: 12 TLS-related chemokines in TCGA database were analyzed to investigate the TLSs in OSCC. The density, maturity, and location of TLSs in a large cohort of 189 OSCC patients (114 of which had clinical and prognostic information) were assessed. And the significance between TLSs and clinicopathologic characteristics was analyzed. RESULTS: Bioinformatics and analysis showed that TLSs were associated with better clinical outcomes in OSCC. Histological staining and analysis showed that the overall survival rate of the high-density group (71/112, 63.4%) was significantly higher (p < 0.0001) than that of the low-density group (41/112, 36.6%), and the high-density group had fewer lymph node metastases (50.0%/68.3%, p = 0.021). And TLSs were divided into 4 types according to the maturity and location. Different types of TLSs are associated with prognosis (OS, p < 0.0001), clinical features (T stage, p = 0.028; degree of differentiation, p = 0.043), and precancerous lesion types (OSF, p = 0.049) of OSCC patients. CONCLUSION: TLSs were closely associated with better OSCC prognosis, and a more systematic classification may better guide the formulation of further treatment options.
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Hepatocellular carcinoma (HCC) was characterized as being hypervascular. In the present study, we generated a single-cell spatial transcriptomic landscape of the vasculogenic etiology of HCC and illustrated overexpressed Golgi phosphoprotein 73 (GP73) HCC cells exerting cellular communication with vascular endothelial cells with high pro-angiogenesis potential via multiple receptor-ligand interactions in the process of tumor vascular development. Specifically, we uncovered an interactive GP73-mediated regulatory network coordinated with c-Myc, lactate, Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway, and endoplasmic reticulum stress (ERS) signals in HCC cells and elucidated its pro-angiogenic roles in vitro and in vivo. Mechanistically, we found that GP73, the pivotal hub gene, was activated by histone lactylation and c-Myc, which stimulated the phosphorylation of downstream STAT3 by directly binding STAT3 and simultaneously enhancing glucose-regulated protein 78 (GRP78)-induced ERS. STAT3 potentiates GP73-mediated pro-angiogenic functions. Clinically, serum GP73 levels were positively correlated with HCC response to anti-angiogenic regimens and were essential for a prognostic nomogram showing good predictive performance for determining 6-month and 1-year survival in patients with HCC treated with anti-angiogenic therapy. Taken together, the aforementioned data characterized the pro-angiogenic roles and mechanisms of a GP73-mediated network and proved that GP73 is a crucial tumor angiogenesis niche gene with favorable anti-angiogenic potential in the treatment of HCC.
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Organic hole transporting materials (HTMs) are extensively studied in perovskite solar cells (PSCs). The HTMs directly contact the underlying perovskite material, and they play additional roles apart from hole transporting. Developing organic HTMs with defect passivation function has been proved to be an efficient strategy to construct efficient and stable PSCs. In this work, new organic molecules with thiocarbonyl (CâS) and carbonyl (CâO) functional groups are synthesized and applied as HTMs (named FN-S and FN-O). FN-S with CâS can be facilely obtained from FN-O containing CâO. Notably, the CâS in FN-S results in superior defect passivation ability compared to FN-O. Moreover, FN-S exhibits excellent hole extraction/transport capability. Conventional PSCs using FN-S as HTM show an impressive power conversion efficiency (PCE) of 23.25%, with excellent long-term stability and operational stability. This work indicates that simply converting CâO to CâS is an efficient way to improve the device performance by strengthening the defect passivation functionality.
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The swift advancement of the solid oxide fuel cell (SOFC) sector necessitates a harmony between electrode performance and commercialization cost. The economic value of elements is frequently linked to their abundance in the Earth's crust. Here, we develop abundant rare-earth iron perovskite electrodes of Ln0.6Sr0.4FeO3-δ (Ln = La, Pr, and Nd) with high abundant rare-earth metals and preferred iron metal for SOFCs. All three symmetric electrode materials display a cubic perovskite phase and excellent chemical compatibility with Gd0.2Ce0.8O2-δ electrolyte. All three electrodes possess exceptional surface oxygen exchange ability. At 800°C, single cells with La0.6Sr0.4FeO3-δ, Pr0.6Sr0.4FeO3-δ, and Nd0.6Sr0.4FeO3-δ symmetric electrodes attained excellent open circuit voltages of 1.108, 1.101, and 1.097 V, respectively, as well as peak powers of 213.52, 281.12, and 254.58 mW cm-2. The results suggest that overall performance of abundant rare-earth iron perovskite electrodes has a favorable impact on the extensive expansion of SOFCs, presenting significant potential for practical applications.
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Despite the importance of interregional skilled migration to regional development, few studies have explored its spatial spillover effects and their changes over time. Thus, employing the Spatial Durbin Model, we investigate the presence of regional spillovers of skilled migration at both national and sub-national levels in China. Especially, we focus on the regional difference and change in the spatial spillover. Although our results confirm positive spillover effects at the national level due to the strong mobility characteristic of skilled migrants, developed regions benefit more from spillovers of skilled migration than developing regions, and such effects are divergent in different regions over time. Our findings also indicate that changes in spatial spillovers among regions are closely associated with the mobility of economic factors in geography. Theoretically, by considering the spatial effects of skilled migration on the innovation output of recipient regions, we extend the labour economics literature into geographical economic agglomeration, especially innovation economic geography. Methodologically, we examine the spatial effects at both national and sub-national levels, and capture the spatial externalities; we also apply Maximum Likelihood estimation to assess the endogeneity issues to understand the mechanisms of spillover change over time. The study can be of significance for municipalities in the policy-making of attracting talents and promoting regional innovation.
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Exercício Físico , Estudantes , Humanos , China , Adolescente , Criança , Feminino , MasculinoRESUMO
NF2-related Schwannomatosis (NF2-SWN) is a disease that needs new solutions. The hallmark of NF2-SWN, a dominantly inherited neoplasia syndrome, is bilateral vestibular schwannomas (VSs), which progressively enlarge, leading to sensorineural hearing loss, tinnitus, facial weakness, and pain that translates to social impairment and clinical depression. Standard treatments for growing VSs include surgery and radiation therapy (RT); however, both carry the risk of further nerve damage that can result in deafness and facial palsy. The resultant suffering and debility, in combination with the paucity of therapeutic options, make the effective treatment of NF2-SWN a major unmet medical need. A better understanding of these mechanisms is essential to developing novel therapeutic targets to control tumor growth and improve patients' quality of life. Previously, we developed the first orthotopic cerebellopontine angle mouse model of VSs, which faithfully mimics tumor-induced hearing loss. In this model, we observed that mice exhibit symptoms of ataxia and vestibular dysfunction. Therefore, we further developed a panel of five tests suitable for the mouse VS model and investigated how tumor growth and treatment affect gait, coordination, and motor function. Using this panel of ataxia tests, we demonstrated that both ataxia and motor function deteriorated concomitantly with tumor progression. We further demonstrated that (i) treatment with anti-VEGF resulted in tumor size reduction, mitigated ataxia, and improved rotarod performance; (ii) treatment with crizotinib stabilized tumor growth and led to improvements in both ataxia and rotarod performance; and (iii) treatment with losartan did not impact tumor growth nor ameliorate ataxia or motor function. Our studies demonstrated that these methods, paired with hearing tests, enable a comprehensive evaluation of tumor-induced neurological deficits and facilitate the assessment of the effectiveness of novel therapeutics to improve NF2 treatments.
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Constructing unique heterostructures is a highly effective approach for enhancing the K+ storage capability of transition metal selenides. Such structures generate internal electric fields that significantly reduce the charge transfer activation energy. However, achieving a flawless interfacial region that maintains the optimal energy level gradient and degree of lattice matching remains a considerable challenge. In this study, we synthesised Setaria-like NiTe2/MoS2@C heterogeneous interfaces at which three-dimensional MoS2 nanosheets are evenly embedded in NiTe2 nanorods to form stabilised heterojunctions. The NiTe2/MoS2 heterojunctions display distinctive electronic configurations and several active sites owing to their low lattice misfits (δ = 13 %), strong electric fields, and uniform carbon shells. A NiTe2/MoS2@C anode in a potassium-ion battery (KIB) exhibited an impressive reversible capacity of 125.8 mAh/g after 1000 cycles at a rate of 500 mA g-1 and a stable reversible capacity of 111.7 mAh/g even after 3000 cycles at 1000 mA g-1. Even the NiTe2/MoS2@C//perylene tetracarboxylic dianhydride full battery configuration maintained a significant reversible capacity of 92.4 mAh/g after 100 cycles at 200 mA g-1, highlighting its considerable potential for application in KIBs. Calculations further revealed that the well-designed NiTe2/MoS2 heterojunction significantly promotes K+ ion diffusion.
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Exposure to disasters and public health emergencies negatively affects mental health. Research documenting the psychosocial responses to these calamities in China increased dramatically after the 2008 Wenchuan earthquake. However, there is no comprehensive assessment of the available literature on China's mental health and psychosocial support (MHPSS) responses to these events. This scoping review systematically maps existing published research and grey literature sources regarding MHPSS to disasters and emergencies in China. We examined relevant literature in English and Chinese from six databases and official websites from Jan 1, 2000, to Aug 13, 2021, and included 77 full-text records in this review. The main types of interventions reported included a) stepped care intervention models, b) individual structured psychotherapy and pharmacotherapy, c) mental health education, d) psychological counselling, and e) government-based policy interventions. Most interventions were evaluated using quantitative methods that assessed the treatment of common mental disorders. The review found that rapid national mobilization, emphasis on resilience-strengthening interventions, and the widespread use of step-care models were essential components of reducing the adverse psychosocial effects of disasters. The review also identified remaining gaps, including a) a lack of integration of disaster-related services with the pre-existing health care system, b) inadequate supervision of MHPSS providers, and c) limited monitoring and evaluation of the services provided. These results show where additional research is needed in China to improve mental health services. It also provides a framework that other countries can adapt when developing and evaluating MHPSS policies and plans in response to disasters.
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Management of functional groups in hole transporting materials (HTMs) is a feasible strategy to improve perovskite solar cells (PSCs) efficiency. Therefore, starting from the carbazole-diphenylamine-based JY7 molecule, JY8 and JY9 molecules are incorporated into the different electron-withdrawing groups of fluorine and cyano groups on the side chains. The theoretical results reveal that the introduction of electron-withdrawing groups of JY8 and JY9 can improve these highest occupied molecular orbital (HOMO) energy levels, intermolecular stacking arrangements, and stronger interface adsorption on the perovskite. Especially, the results of molecular dynamics (MD) indicate that the fluorinated JY8 molecule can yield a preferred surface orientation, which exhibits stronger interface adsorption on the perovskite. To validate the computational model, the JY7-JY9 are synthesized and assembled into PSC devices. Experimental results confirm that the HTMs of JY8 exhibit outstanding performance, such as high hole mobility, low defect density, and efficient hole extraction. Consequently, the PSC devices based on JY8 achieve a higher PCE than those of JY7 and JY9. This work highlights the management of the electron-withdrawing groups in HTMs to realize the goal of designing HTMs for the improvement of PSC efficiency.