A highly birefringent metal-free crystal assembled by cooperative non-covalent interactions.

Birefringent crystals can manipulate the phase and polarization of light, so they are widely used as essential components in various optical devices. Common strategies to construct birefringent crystals are introducing metal cations that are either able to realize favorable coordination with functional anionic units or are susceptible to polarizability anisotropy. Herein, we report a metal-free crystal, NH4(H2C6N7O3)·2H2O, synthesized using the facile solution method. In the crystal structure of NH4(H2C6N7O3)·2H2O, (H2C6N7O3)- functional units are assembled in an optimal manner by cooperative non-covalent interactions, i.e., hydrogen bonding and π-π interactions. As a result, this metal-free crystal possesses exceptional birefringence up to 0.54@550 nm, which is larger than those of most metal-containing birefringent crystals. In addition, the interference color of this crystal does not change obviously from 243 K to 313 K, indicating that the birefringence is robust at different temperatures. This work will inspire useful insights into the role of non-covalent interactions in designing outstanding birefringent crystals for efficient polarized optical devices.

Deep-Ultraviolet Bialkali-Rare Earth Metal Anhydrous Sulfate Birefringent Crystal.

Birefringence is an important linear optical property of anisotropic crystals that plays a significant role in regulating light polarization. A new bialkali-rare earth metal sulfate, NaRbY2(SO4)4 compound, consisting of non-π-conjugated alkali metals and rare earth metal-centered dodecahedral YO8 has been synthesized. The structure analysis suggests that the three-dimensional (3D) structure of the compound is found to be attributable to the combination of dodecahedral YO8 and tetrahedral SO4 groups with Na+ and Rb+ located in the cavities. The ultraviolet, visible, and near-infrared (UV-vis-NIR) spectra reveal that the compound exhibits transparency at a wavelength of less than 200 nm. The observed birefringence of the compound is 0.045@550 nm, which is comparatively larger than that of most deep-ultraviolet (DUV) birefringent crystals. The birefringence mainly originated from the YO8 dodecahedron, which is suggested by first-principles calculations. This research work can provide a useful perspective to explore new DUV sulfates with excellent birefringence.

Prospective prediction of anxiety onset in the Canadian longitudinal study on aging (CLSA): A machine learning study.

BACKGROUND: Anxiety disorders are among the most common mental health disorders in the middle aged and older population. Because older individuals are more likely to have multiple comorbidities or increased frailty, the impact of anxiety disorders on their overall well-being is exacerbated. Early identification of anxiety disorders using machine learning (ML) can potentially mitigate the adverse consequences associated with these disorders. METHODS: We applied ML to the data from the Canadian Longitudinal Study on Aging (CLSA) to predict the onset of anxiety disorders approximately three years in the future. We used Shapley value-based methods to determine the top factor for prediction. We also investigated whether anxiety onset can be predicted by baseline depression-related predictors alone. RESULTS: Our model was able to predict anxiety onset accurately (Area under the Receiver Operating Characteristic Curve or AUC = 0.814 ± 0.016 (mean ± standard deviation), balanced accuracy = 0.741 ± 0.016, sensitivity = 0.743 ± 0.033, and specificity = 0.738 ± 0.010). The top predictive factors included prior depression or mood disorder diagnosis, high frailty, anxious personality, and low emotional stability. Depression and mood disorders are well known comorbidity of anxiety; however a prior depression or mood disorder diagnosis could not predict anxiety onset without other factors. LIMITATION: While our findings underscore the importance of a prior depression diagnosis in predicting anxiety, they also highlight that it alone is inadequate, signifying the necessity to incorporate additional predictors for improved prediction accuracy. CONCLUSION: Our study showcases promising prospects for using machine learning to develop personalized prediction models for anxiety onset in middle-aged and older adults using easy-to-access survey data.

Fatty acid esters of hydroxy fatty acids: A potential treatment for obesity-related diseases.

Obesity, a burgeoning worldwide health system challenge, is associated with multiple chronic diseases, including diabetes and chronic inflammation. Fatty acid esters of hydroxy fatty acids (FAHFAs) are newly identified lipids with mitigating and anti-inflammatory effects in diabetes. Increasing work has shown that FAHFAs exert antioxidant activity and enhance autophagy in neuronal cells and cardiomyocytes. We systematically summarized the biological activities of FAHFAs, including their regulatory effects on diabetes and inflammation, antioxidant activity, and autophagy augmentation. Notably, the structure-activity relationships and potential biosynthesis of FAHFAs are thoroughly discussed. FAHFAs also showed potential roles as diagnostic biomarkers. FAHFAs are a class of resources with promising applications in the biomedical field that require in-depth research and hotspot development, as their structure has not been fully resolved and their biological activity has not been fully revealed.

Designing a Hybrid Perovskite with Enlarged Birefringence and Bandgap for Modulation of Light Polarization.

Birefringent crystals have important applications in optoelectronics areas due to their ability to modulate and polarize light. Despite increasing discovery of the birefringence potential of new crystals, it remains a great challenge to optimize both birefringence and bandgap simultaneously. Herein, a 1D chain-like hybrid perovskite birefringent crystal designed by 3D-to-1D dimensional tailoring, (GAM)2 PbI7 ·H2 O (GAM = C5 N10 H10 ), is presented, showing enlarged birefringence of 0.49@550 nm and enlarged optical bandgap (2.48 eV). Consequently, the birefringent quality factor of (GAM)2 PbI7 ·H2 O is up to 2.8 times that of the template MAPbI3 . In particular, the birefringence is much larger than those of commercial birefringent crystals and surpasses that of the vast majority of hybrid perovskite known to date. Theoretical calculations reveal that the strongly anisotropic arrangement of (GAM)2.5+ π-conjugated cations and ordered PbI6 octahedra contributes to the large birefringence and wide bandgap of (GAM)2 PbI7 ·H2 O. It is believed that this work will provide a new pathway toward the rational design and synthesis of hybrid perovskite birefringent crystals for compact wide-bandgap polarization dependent devices.

Associations between Differential Aging and Lifestyle, Environment, Current, and Future Health Conditions: Findings from Canadian Longitudinal Study on Aging.

INTRODUCTION: An aging population will bring a pressing challenge for the healthcare system. Insights into promoting healthy longevity can be gained by quantifying the biological aging process and understanding the roles of modifiable lifestyle and environmental factors, and chronic disease conditions. METHODS: We developed a biological age (BioAge) index by applying multiple state-of-art machine learning models based on easily accessible blood test data from the Canadian Longitudinal Study of Aging (CLSA). The BioAge gap, which is the difference between BioAge index and chronological age, was used to quantify the differential aging, i.e., the difference between biological and chronological age, of the CLSA participants. We further investigated the associations between the BioAge gap and lifestyle, environmental factors, and current and future health conditions. RESULTS: BioAge gap had strong associations with existing adverse health conditions (e.g., cancers, cardiovascular diseases, diabetes, and kidney diseases) and future disease onset (e.g., Parkinson's disease, diabetes, and kidney diseases). We identified that frequent consumption of processed meat, pork, beef, and chicken, poor outcomes in nutritional risk screening, cigarette smoking, exposure to passive smoking are associated with positive BioAge gap ("older" BioAge than expected). We also identified several modifiable factors, including eating fruits, legumes, vegetables, related to negative BioAge gap ("younger" BioAge than expected). CONCLUSIONS: Our study shows that a BioAge index based on easily accessible blood tests has the potential to quantify the differential biological aging process that can be associated with current and future adverse health events. The identified risk and protective factors for differential aging indicated by BioAge gap are informative for future research and guidelines to promote healthy longevity.

A Two-Dimensional Hybrid Perovskite With Heat Switching Birefringence.

Birefringent crystals that can switch light polarization have important applications in optoelectronics. In the last decades, birefringence is mostly optimized by chemical strategies. Recently, switching birefringence by physical means has attracted much attention. Here, this work reports the observation of heat switching birefringence in a 2D layered hybrid halide perovskite (C2 N3 H4 )2 PbCl4 ((C2 N3 H4 )+ =1,2,4-triazolium). This heat switching birefringence leads to a significant change in the interference color for the crystal plate under the illumination of orthogonal polarized light. Structure analyses reveal a heat dependent structure transition in (C2 N3 H4 )2 PbCl4 , whose birefringence is switched by the change in the distortion degree of PbCl6 octahedron. This discovery may be beneficial to the further development of stimuli-responsive polarization optical devices.

Tumor to liver maximum standardized uptake value ratio of FDG-PET/CT parameters predicts tumor treatment response and survival of stage III non-small cell lung cancer.

BACKGROUND: To assess the predictive values of primary tumor FDG uptake for patients with inoperable stage III non-small cell lung cancer (NSCLC) after concurrent chemoradiotherapy (CCRT). METHODS: A total of 107 patients with diagnosis of stage III NSCLC and CCRT were enrolled. The tumor maximum uptake value (SUVmax) was standardized by calculating several ratios between tumor and each background tissues. The receiver operating characteristics curve (ROC) was used to compare the predictive power of prognostic models. The tumor objective response rate (ORR) and overall survival (OS) were compared and analyzed by the Kaplan-Meier method and univariate and multivariate Cox regression models. RESULTS: The areas under ROC curve (AUCs) ranged from 0.72 to 0.81 among these tumor SUVmax and standardized SUVmax ratios, and the tumor SUVmax and tumor SUVmax-to-liver SUVmean ratio (TLMR) were more predictive of ORR (AUC, 0.81; 95% CI, 0.73-0.88 for tumor SUVmax and AUC, 0.84; 95%CI, 0.76-0.91 for TLMR) than any of other SUVmax ratios. The patients with lower tumor SUVmax, SUVmean and SUVmax ratios had a significantly better OS than those with their corresponding higher ones. Moreover, both univariate and multivariable analyses revealed that TLMR was significantly associated with better ORR and OS after adjustment with other prognostic variables. CONCLUSIONS: TLMR, a standardized tumor SUVmax, was an independent prognostic predictor for tumor ORR and OS of patients with stage III NSCLC after CCRT.

Prediction of depression onset risk among middle-aged and elderly adults using machine learning and Canadian Longitudinal Study on Aging cohort.

BACKGROUND: Early identification of the middle-aged and elderly people with high risk of developing depression disorder in the future and the full characterization of the associated risk factors are crucial for early interventions to prevent depression among the aging population. METHODS: Canadian Longitudinal Study on Aging (CLSA) has collected comprehensive information, including psychological scales and other non-psychological measures, i.e., socioeconomic, environmental, health, lifestyle, cognitive function, personality, about its participants (30,097 subjects aged from 45 to 85) at baseline phase in 2012-2015. We applied machine learning models for the prediction of these participants' risk of depression onset approximately three years later using information collected at baseline phase. RESULTS: Individual-level risk for future depression onset among CLSA participants can be accurately predicted, with an area under receiver operating characteristic curve (AUC) 0.791 ± 0.016, using all baseline information. We also found the 10-item Center for Epidemiological Studies Depression Scale coupled with age and sex information could achieve similar performance (AUC 0.764 ± 0.016). Furthermore, we identified existing subthreshold depression symptoms, emotional instability, low levels of life satisfaction, perceived health, and social support, and nutrition risk as the most important predictors for depression onset independent from psychological scales. LIMITATIONS: Depression was based on self-reported doctor diagnosis and depression screening tool. CONCLUSIONS: The identified risk factors will further improve our understanding of the depression onset among middle-aged and elderly population and the early identification of high-risk subjects is the first step for successful early interventions.

Comprehensive Analysis Reveals the Potential Roles of Transcription Factor Dp-1 in Lung Adenocarcinoma.

Background: Transcription factor Dp-1 (TFDP1) was overexpressed and interacted with other genes to impact multiple signaling pathways in various human cancers. However, there is less research about the TFDP1 specific roles in lung adenocarcinoma (LUAD). Methods: We first explored TFDP1 expression levels and relative diseases from a pan-cancer perspective using the ONCOMINE, TIMER, and Open Targets Platform databases. Then, we used UALCAN, GEPIA 2, TCGA-LUAD data, and Kaplan-Meier plotter to examine TFDP1 clinicopathological features and prognosis in LUAD patients. Genomic alterations and DNA methylation analysis were performed by cBioPortal and MethSurv, respectively. Then, we used a cancer single-cell state atlas (CancerSEA) to find TFDP1 functions at a single-cell resolution. LinkedOmics was used to find TFDP1 coexpressed genes, biological processes, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Then, Gene Set Cancer Analysis (GSCA) was used to examine the drug resistence of TFDP1 in LUAD. Results: We found that TFDP1 was overexpressed in most human cancers and related to various diseases, including LUAD. Moreover, LUAD patients with high TFDP1 expression levels might be significantly associated with individual cancer stages and have a poor prognosis. Multivariate analysis revealed that the American Joint Committee on Cancer (AJCC) pathologic stage, AJCC stage T, and AJCC stage N were the independent prognostic factors. LUAD patients with TFDP1 alterations suggested poor overall survival (OS), and disease-free survival (DFS), while hypermethylation might lead to a good prognosis. TFDP1 and its coexpressed genes were enriched in multiple signaling pathways and biological processes involved in the cell cycle, spliceosome, and DNA replication. Furthermore, TFDP1 was strongly positively related to the half-maximal inhibitory concentration (IC50) values of multiple drugs. Conclusions: In summary, TFDP1 was a possible biomarker and potential therapeutic target for LUAD patients.

A Hydrogen Bonded Supramolecular Framework Birefringent Crystal.

Birefringent crystals could modulate the polarization of light and are widely used as polarizers, waveplates, optical isolators, etc. To date, commercial birefringent crystals have been exclusively limited to purely inorganic compounds such as α-BaB2 O4 with birefringence of about 0.12. Herein, we report a new hydrogen bonded supramolecular framework, namely, Cd(H2 C6 N7 O3 )2 ⋅8 H2 O, which exhibits exceptionally large birefringence up to about 0.60. To the best of our knowledge, the birefringence of Cd(H2 C6 N7 O3 )2 ⋅8 H2 O is significantly larger than those of all commercial birefringent crystals and is the largest among hydrogen bonded supramolecular framework crystals. First-principles calculations and structural analyses reveal that the exceptional birefringence is mainly ascribed to strong covalent interactions within (H2 C6 N7 O3 )- organic ligands and the perfect coplanarity between them. Given the rich structural diversity and tunability, hydrogen bonded supramolecular frameworks would offer unprecedented opportunities beyond the traditional purely inorganic oxides for birefringent crystals.

Analysis and Validation of the Prognosis ability of the M7GRelated miRNAs in Lung Adenocarcinoma.

BACKGROUND: N7-methylguanosine (m7G) modification plays a crucial role in the development and progression of lung cancers. MicroRNAs (miRNAs) are closely involved in programmed cell death and the mechanism of tumor growth. The m7G-associated miRNAs genes in lung adenocarcinoma (LUAD), and their prognosis prediction ability of LUAD, however, had not been investigated. METHODS: The RNA transcriptomes, clinical indices, and immune scores of LUAD patients were searched and downloaded from The Cancer Genome Atlas (TCGA) and the ESTIMATE database. The miRNAs targeting METTL1 and WDR4 were extracted from the TargetScan database. Differentially expressed m7G-related miRNAs were identified and their prediction power of LUAD prognosis was systematically investigated. RESULTS: Among 40 the differentially expressed m7G-related miRNAs in LUAD, five (hsa-miR-31-5p, hsa-miR-5571-3p, hsa-miR-4697-3p, hsa-miR-6858-5p, and hsa-miR-873-3p) demonstrate significant predictive value for prognosis. The risk score constructed by these five miRNAs was an independent prognostic factor (univariate Cox regression results: hazard ratio (HR) = 1.6619, 95% confidential interval (CI) = 1.2103-2.2819, p = 0.0017; multivariate Cox regression results: HR = 1.6004, 95% CI = 1.1633-2.2017, p = 0.0039). The survival curves showed that patients with high-risk scores had a poor prognosis. Calibration curves indicated good predictability in a nomogram constructed combining the miRNA and the clinical indices of age, sex, chemotherapy, radiotherapy, stage, and risk score. GO and KEGG analysis of the overlapping genes showed that the prognostic miRNAs were closely associated with the neuropeptide signaling pathway. Besides, the immune infiltration analysis showed that the expression of the AMPD1 gene was strongly associated with immune cells and immunology functions in LUAD. CONCLUSION: This study identified DE m7G-related miRNAs and demonstrated their prediction ability in the prognosis of LUAD patients. The risk signature based on these miRNAs demonstrates high accuracy in predicting the prognosis of LUAD patients.

A Second-Order Nonlinear Optical Material Consisting of Two π-Conjugated Groups.

This work reports a new second-order nonlinear optical (NLO) material [C(NH2 )3 ]3 C3 N3 S3 (GU3 TMT), consisting of π-conjugated planar (C3 N3 S3 )3- and triangular [C(NH2 )3 ]+ groups. Interestingly, GU3 TMT exhibits a large NLO response (2.0×KH2 PO4 ) and moderate birefringence 0.067 at wavelength 550 nm, even though (C3 N3 S3 )3- and [C(NH2 )3 ]+ do not exhibit the most favorable arrangement in the structure of GU3 TMT. First-principles calculations suggest that NLO properties mainly originate from the highly π-conjugated (C3 N3 S3 )3- rings, and the π-conjugated [C(NH2 )3 ]+ triangles contribute much less to the overall NLO response. This work will inspire new thoughts with in-depth on the role of π-conjugated groups in NLO crystals.

Prognostic roles of a novel basement membranes-related gene signature in lung adenocarcinoma.

Background: The basement membranes (BMs) are involved in tumor progression, while few comprehensive analyses to date are performed on the role of BM-related gene signatures in lung adenocarcinoma (LUAD). Thus, we aimed to develop a novel prognostic model in LUAD based on BMs-related gene profiling. Methods: The LUAD BMs-related gene profiling and corresponding clinicopathological data were obtained from the basement membrane BASE, The Cancer Genome Atlas (TCGA) and gene expression omnibus (GEO) databases. The Cox regression and least absolute shrinkage and selection operator (LASSO) methods were used to construct a BMs-based risk signature. The concordance index (C-index), receiver operating characteristic (ROC), and calibration curves were generated to evaluate the nomogram. The GSE72094 dataset was used to validate prediction of the signature. The differences in functional enrichment, immune infiltration, and drug sensitivity analyses were compared based on risk score. Results: In TCGA training cohort, 10 BMs-related genes were found, (e.g., ACAN, ADAMTS15, ADAMTS8, BCAN, etc). The signal signature based on these 10 genes was categorized into high- and low-risk groups regarding survival differences (p < 0.001). Multivariable analysis showed that the signature of combined 10 BMs-related genes was an independent prognostic predictor. Such a prognostic value of BMs-based signature in validation cohort of the GSE72094 were further verified. The GEO verification, C-index, and ROC curve showed that the nomogram had accurate prediction performance. The functional analysis suggested that BMs were mainly enriched in extracellular matrix-receptor (ECM-receptor) interaction. Moreover, the BMs-based model was correlated with immune checkpoint. Conclusion: This study identified BMs-based risk signature genes and demonstrated their ability to predict prognosis and guide personalized treatment of patients with LUAD.

A High-Performance Nonlinear Optical Crystal with a Building Block Containing Expanded π-Delocalization.

Common nonlinear optical (NLO) crystals consist of traditional functional building blocks with inherent optical limitation. Herein, inspired by traditional (B3 O6 )3- inorganic building block, we theoretically identified a new type of organic functional building blocks and then successfully synthesized the first cyamelurate NLO crystal, Ba(H2 C6 N7 O3 )2 ⋅ 8 H2 O. To our surprise, the constituent (H2 C6 N7 O3 )- building block is not in structurally optimal arrangement, but Ba(H2 C6 N7 O3 )2 ⋅ 8 H2 O exhibits excellent optical properties including wide band gap of 4.10 eV, very large birefringence of 0.24@550 nm, and exceptionally strong second-harmonic generation (SHG) response of about 12×KH2 PO4 . Both the SHG response and birefringence are much larger than those of commercial NLO crystal ß-BaB2 O4 with optimally aligned (B3 O6 )3- building block. Theoretical calculations suggest that the expanded π-conjugation delocalization within (H2 C6 N7 O3 )- vs (B3 O6 )3- should be responsible to the enhanced performance. This work implies that there is still much room to develop new NLO crystals with excellent functional building blocks that may be longly neglected.

A Hybrid Antiperovskite with Strong Linear and Second-Order Nonlinear Optical Responses.

Antiperovskites have been studied since the 1980s because of their rich physical and chemical properties, but their linear and second-order nonlinear optical responses remain largely unknown. Here we report a new polar crystal, Cs3 Cl(HC3 N3 S3 ) (I), which features a quasi-one-dimensional antiperovskite structure composed of ClCs6 polyhedra and A-site [HC3 N3 S3 ]2- rings. To our best knowledge, this kind of antiperovskite structure is reported for the first time. Remarkably, I exhibits a very strong nonlinear optical response up to 11.4 times that of the benchmark KH2 PO4 and exceptionally large birefringence of 0.52. The first-principles calculations and structural analyses reveal that [HC3 N3 S3 ]2- is the "material gene" while the antiperovskite structural feature making it in a favorable arrangement. This work provides a new structural platform for the rational design of integrated optoelectronic materials with linear and second-order nonlinear optical responses.

Restoration of cefixime-induced gut microbiota changes by a prebiotic blend in a mouse model.

Recent studies have provided compelling evidence linking the composition of the gut microbiota, host diet, and host physiology. Prebiotics are substrates that are selectively utilized by host microorganisms, conferring health benefits. Prebiotics, such as prebiotic blends (PB), are commonly used worldwide in food processing. Here, microbiome-metabolomics was used to evaluate how PB affect gut microbes and metabolic functions in C57BL/6 J mice administered cefixime. We found favorable effects of PB on obesity outcomes. PB supplementation significantly increased the abundance of Bifidobacterium, Parabacteroides, Alloprevotella, Alistipes, and Dubosiella, and decreased that of Robinsoniella, Blautia, Lachnoclostridium, Coprobacillus, Hungatella, Erysipelatoclostridium, Helicobacter, Clostridium sensu stricto 1, Enterococcus, and Akkermansia compared to that in the cefixime administration (CEF) group. In particular, PB increased the abundance of Parabacteroides goldsteinii and suppressed that of Robinsoniella peoriensis and Akkermansia muciniphila. In addition, it regulated the levels of microbial metabolites such as unsaturated fatty acids and bile acids. Thus, PB can alleviate metabolic disorders induced by antibiotic intervention, indicating a potential dietary strategy for populations with antibiotic-associated diarrhea. KEY POINTS: • Prebiotic blends significantly increased the Parabacteroides goldsteinii colony. • Prebiotic blends selectivity reversed this increase of Akkermansia muciniphila by antibiotic intervention. • Prebiotic blends relieve cefixime-induced alteration of intestinal flora by regulating metabolites, such as fatty acids and bile acids.

An Optically Anisotropic Crystal with Large Birefringence Arising from Cooperative π Orbitals.

Birefringent materials are highly demanded for high-performance polarized optics. As compared with artificial anisotropic metamaterials, anisotropic crystals have advantages of low optical losses and easy processing, but their birefringence is still limited. Herein, based on first-principles studies, we identified a new type of functional anion units, (Hx C6 N9 )(3-x)- (x=0, 1, 2), and then successfully synthesized a new anisotropic crystal, namely, CsH2 C6 N9 ⋅H2 O (I), whose crystal structure consists of (H2 C6 N9 )- anions. Remarkably, I is ultraviolet transparent and exhibits very large birefringence of about 0.55@550 nm, which is much larger than those of commercial birefringent crystals. These results make I a candidate for highly efficient manipulation of optics and light in optical modulation devices. Theoretical calculations reveal that large birefringence mainly arises from the cooperative π orbitals in (H2 C6 N9 )- anions. This work provides a new insight on the underlying structure-property relationships of anisotropic crystals.

Identifying the Potential Roles of PBX4 in Human Cancers Based on Integrative Analysis.

PBX4 belongs to the pre-B-cell leukemia homeobox (PBX) transcription factors family and acts as a transcriptional cofactor of HOX proteins participating in several pathophysiological processes. Recent studies have revealed that the dysregulation of PBX4 is closely related to multiple diseases, especially cancers. However, the research on PBX4's potential roles in 33 cancers from the Cancer Genome Atlas (TCGA) is still insufficient. Therefore, we performed a comprehensive pan-cancer analysis to explore the roles of PBX4with multiple public databases. Our results showed that PBX4 was differentially expressed in 17 types of human cancer and significantly correlated to the pathological stage, tumor grade, and immune and molecular subtypes. We used the Kaplan-Meier plotter and PrognoScan databases to find the significant associations between PBX4 expression and prognostic values of multiple cancers. It was also found that PBX4 expression was statistically related to mutation status, DNA methylation, immune infiltration, drug sensitivity, and immune checkpoint blockade (ICB) therapy. Additionally, we found that PBX4 was involved in different functional states of multiple cancers from the single-cell resolution perspective. Enrichment analysis results showed that PBX4-related genes were enriched in the cell cycle process, MAPK cascade, ncRNA metabolic process, positive regulation of GTPase activity, and regulation of lipase activity and mainly participated in the pathways of cholesterol metabolism, base excision repair, herpes simplex virus 1 infection, transcriptional misregulation in cancer, and Epstein-Barr virus infection. Altogether, our integrative analysis could help in better understanding the potential roles of PBX4 in different human cancers.