Ferroelectricity and Thermochromism in a 2D Dion-Jacobson Organic-Inorganic Hybrid Perovskite.

2D organic-inorganic hybrid perovskites (OIHPs) have become one of the hottest research topics due to their excellent environmental stability and unique optoelectronic properties. Recently, the ferroelectricity and thermochromism of 2D OIHPs have attracted increasing interests. Integrating ferroelectricity and thermochromism into perovskites can significantly promote the development of multichannel intelligent devices. Here, a novel 2D Dion-Jacobson OIHP of the formula (3AMP)PbI4 (where 3AMP is 3-(aminomethyl)pyridinium) is reported, which has a remarkable spontaneous polarization value (Ps) of 15.6 µC cm-2 and interesting thermochromism. As far it is known, such a large Ps value is the highest for 2D OIHPs recorded so far. These findings will inspire further exploration and application of multifunctional perovskites.

Dual-Drug Nanomedicine Assembly with Synergistic Anti-Aneurysmal Effects via Inflammation Suppression and Extracellular Matrix Stabilization.

Abdominal aortic aneurysm (AAA) represents a critical cardiovascular condition characterized by localized dilation of the abdominal aorta, carrying a significant risk of rupture and mortality. Current treatment options are limited, necessitating novel therapeutic approaches. This study investigates the potential of a pioneering nanodrug delivery system, RAP@PFB, in mitigating AAA progression. RAP@PFB integrates pentagalloyl glucose (PGG) and rapamycin (RAP) within a metal-organic-framework (MOF) structure through a facile assembly process, ensuring remarkable drug loading capacity and colloidal stability. The synergistic effects of PGG, a polyphenolic antioxidant, and RAP, an mTOR inhibitor, collectively regulate key players in AAA pathogenesis, such as macrophages and smooth muscle cells (SMCs). In macrophages, RAP@PFB efficiently scavenges various free radicals, suppresses inflammation, and promotes M1-to-M2 phenotype repolarization. In SMCs, it inhibits apoptosis and calcification, thereby stabilizing the extracellular matrix and reducing the risk of AAA rupture. Administered intravenously, RAP@PFB exhibits effective accumulation at the AAA site, demonstrating robust efficacy in reducing AAA progression through multiple mechanisms. Moreover, RAP@PFB demonstrates favorable biosafety profiles, supporting its potential translation into clinical applications for AAA therapy.

Development of preoperative and postoperative models to predict recurrence in postoperative glioma patients: a longitudinal cohort study.

BACKGROUND: Glioma recurrence, subsequent to maximal safe resection, remains a pivotal challenge. This study aimed to identify key clinical predictors influencing recurrence and develop predictive models to enhance neurological diagnostics and therapeutic strategies. METHODS: This longitudinal cohort study with a substantial sample size (n = 2825) included patients with non-recurrent glioma who were pathologically diagnosed and had undergone initial surgical resection between 2010 and 2018. Logistic regression models and stratified Cox proportional hazards models were established with the top 15 clinical variables significantly influencing outcomes screened by the least absolute shrinkage and selection operator (LASSO) method. Preoperative and postoperative models predicting short-term (within 6 months) postoperative recurrence in glioma patients were developed to explore the risk factors associated with short- and long-term recurrence in glioma patients. RESULTS: Preoperative and postoperative logistic models predicting short-term recurrence had accuracies of 0.78 and 0.87, respectively. A range of biological and early symptomatic characteristics linked to short- and long-term recurrence have been pinpointed. Age, headache, muscle weakness, tumor location and Karnofsky score represented significant odd ratios (t > 2.65, p < 0.01) in the preoperative model, while age, WHO grade 4 and chemotherapy or radiotherapy treatments (t > 4.12, p < 0.0001) were most significant in the postoperative period. Postoperative predictive models specifically targeting the glioblastoma and IDH wildtype subgroups were also performed, with an AUC of 0.76 and 0.80, respectively. The 50 combinations of distinct risk factors accommodate diverse recurrence risks among glioma patients, and the nomograms visualizes the results for clinical practice. A stratified Cox model identified many prognostic factors for long-term recurrence, thereby facilitating the enhanced formulation of perioperative care plans for patients, and glioblastoma patients displayed a median progression-free survival (PFS) of only 11 months. CONCLUSION: The constructed preoperative and postoperative models reliably predicted short-term postoperative glioma recurrence in a substantial patient cohort. The combinations risk factors and nomograms enhance the operability of personalized therapeutic strategies and care regimens. Particular emphasis should be placed on patients with recurrence within six months post-surgery, and the corresponding treatment strategies require comprehensive clinical investigation.

Selectively Probing the Magnetic Resonance Signals of γ-Aminobutyric Acid in Human Brains In Vivo.

BACKGROUND: Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter in human brains, playing a role in the pathogenesis of various psychiatric disorders. Current methods have some non-neglectable shortcomings and noninvasive and accurate detection of GABA in human brains is long-term challenge. PURPOSE: To develop a pulse sequence capable of selectively detecting and quantifying the 1 H signal of GABA in human brains based on optimal controlled spin singlet order. STUDY TYPE: Prospective. SUBJECTS/PHANTOM: A phantom of GABA (pH = 7.3 ± 0.1) and 11 healthy subjects (5 females and 6 males, body mass index: 21 ± 3 kg/m2 , age: 25 ± 4 years). FIELD STRENGTH/SEQUENCE: 7 Tesla, 3 Tesla, GABA-targeted magnetic resonance spectroscopy (GABA-MRS-7 T, GABA-MRS-3 T), magnetization prepared two rapid acquisition gradient echoes sequence. ASSESSMENT: By using the developed pulse sequences applied on the phantom and healthy subjects, the signals of GABA were successfully selectively probed. Quantification of the signals yields the concentration of GABA in the dorsal anterior cingulate cortex (dACC) in human brains. STATISTICAL TESTS: Frequency. RESULTS: The 1 H signals of GABA in the phantom and in the human brains of healthy subjects were successfully detected. The concentration of GABA in the dACC of human brains was 3.3 ± 1.5 mM. DATA CONCLUSION: The developed pulse sequences can be used to selectively probe the 1 H MR signals of GABA in human brains in vivo. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY STAGE: 1.

Airway epithelial ITGB4 deficiency induces airway remodeling in a mouse model.

BACKGROUND: Airway epithelial cells (AECs) with impaired barrier function contribute to airway remodeling through the activation of epithelial-mesenchymal trophic units (EMTUs). Although the decreased expression of ITGB4 in AECs is implicated in the pathogenesis of asthma, how ITGB4 deficiency impacts airway remodeling remains obscure. OBJECTIVE: This study aims to determine the effect of epithelial ITGB4 deficiency on the barrier function of AECs, asthma susceptibility, airway remodeling, and EMTU activation. METHODS: AEC-specific ITGB4 conditional knockout mice (ITGB4-/-) were generated and an asthma model was employed by the sensitization and challenge of house dust mite (HDM). EMTU activation-related growth factors were examined in ITGB4-silenced primary human bronchial epithelial cells of healthy subjects after HDM stimulation. Dexamethasone, the inhibitors of JNK phosphorylation or FGF2 were administered for the identification of the molecular mechanisms of airway remodeling in HDM-exposed ITGB4-/- mice. RESULTS: ITGB4 deficiency in AECs enhanced asthma susceptibility and airway remodeling by disrupting airway epithelial barrier function. Aggravated airway remodeling in HDM-exposed ITGB4-/- mice was induced through the enhanced activation of EMTU mediated by Src homology domain 2-containing protein tyrosine phosphatase 2/c-Jun N-terminal kinase/Jun N-terminal kinase-dependent transcription factor/FGF2 (SHP2/JNK/c-Jun/FGF2) signaling pathway, which was partially independent of airway inflammation. Both JNK and FGF2 inhibitors significantly inhibited the aggravated airway remodeling and EMTU activation in HDM-exposed ITGB4-/- mice. CONCLUSIONS: Airway epithelial ITGB4 deficiency induces airway remodeling in a mouse model of asthma through enhanced EMTU activation that is regulated by the SHP2/JNK/c-Jun/FGF2 pathway.

Atomic Ruthenium-Promoted Cadmium Sulfide for Photocatalytic Production of Amino Acids from Biomass Derivatives.

Amino acids are the building blocks of proteins and are widely used as important ingredients for other nitrogen-containing molecules. Here, we report the sustainable production of amino acids from biomass-derived hydroxy acids with high activity under visible-light irradiation and mild conditions, using atomic ruthenium-promoted cadmium sulfide (Ru1/CdS). On a metal basis, the optimized Ru1/CdS exhibits a maximal alanine formation rate of 26.0 molAla ⋅ gRu -1 ⋅ h-1, which is 1.7 times and more than two orders of magnitude higher than that of its nanoparticle counterpart and the conventional thermocatalytic process, respectively. Integrated spectroscopic analysis and density functional theory calculations attribute the high performance of Ru1/CdS to the facilitated charge separation and O-H bond dissociation of the α-hydroxy group, here of lactic acid. The operando nuclear magnetic resonance further infers a unique "double activation" mechanism of both the CH-OH and CH3-CH-OH structures in lactic acid, which significantly accelerates its photocatalytic amination toward alanine.

Patient-derived tumor organoids predict responses to irinotecan-based neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer.

Adding irinotecan to neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC) increases the pathologic complete response (pCR) rate but brings more toxicities. Robust biomarkers to predict response to irinotecan-based nCRT are extremely necessary for selecting the right patients. Our previous study suggests that patient-derived tumor organoids (PDTOs) sensitivity to chemoradiotherapy matches patient responses. In this study, we investigated whether PDTOs sensitivity to irinotecan can predict complete response (CR) and survival. Eligible patients receiving irinotecan-based nCRT between April 5, 2017 and December 11, 2020 were enrolled in the training cohort (n = 91) for response prediction and survival analysis. Patients receiving nCRT between February 21, 2021 and September 17, 2021 were included in the validation cohort (n = 27). Predictive performances of irinotecan organoid size ratio (OSR) for CR or pCR were evaluated. The irinotecan-sensitive groups had higher response rates compared with the insensitive groups (training cohort: 71.8% vs 24.4%, P < .0001; validation cohort, 81.8% vs 18.8%, P = .002). Moreover, the irinotecan-sensitive group had higher rates of 3-year disease-free survival (DFS: 71.6% vs 55.5%, P = .034) and distant metastasis-free survival (DMFS, 77.9% vs 57.2%, P = .015) than the irinotecan-insensitive group. 5-FU and irradiation sensitivities failed to predict 3-year DFS (5-FU: 65.4% vs 61.9%, P = .643; irradiation: 84.8% vs 57.8%; P = .072). Performances of irinotecan OSR to predict CR or pCR were good in the training cohort (CR: AUC = 0.828; 95% CI = 0.723-0.932; pCR: AUC = 0.864; 95% CI = 0.759-0.961). The validation showed robust predictive ability (CR: AUC = 0.796, 95% CI = 0.5974-0.9952; pCR: AUC = 0.917, 95% CI = 0.7921-1.0000). Irinotecan sensitivity in PDTOs was a predictive and prognostic factor in LARC.

The cortical regions and white matter tracts underlying auditory comprehension in patients with primary brain tumor.

The comprehension of spoken language is one of the most essential language functions in humans. However, the neurological underpinnings of auditory comprehension remain under debate. Here we used multi-modal neuroimaging analyses on a group of patients with low-grade gliomas to localize cortical regions and white matter tracts responsible for auditory language comprehension. Region-of-interests and voxel-level whole-brain analyses showed that cortical areas in the posterior temporal lobe are crucial for language comprehension. The fiber integrity assessed with diffusion tensor imaging of the arcuate fasciculus and the inferior longitudinal fasciculus was strongly correlated with both auditory comprehension and the grey matter volume of the inferior temporal and middle temporal gyri. Together, our findings provide direct evidence for an integrated network of auditory comprehension whereby the superior temporal gyrus and sulcus, the posterior parts of the middle and inferior temporal gyri serve as auditory comprehension cortex, and the arcuate fasciculus and the inferior longitudinal fasciculus subserve as crucial structural connectivity. These findings provide critical evidence on the neural underpinnings of language comprehension.

Direct observation of geometric and sliding ferroelectricity in an amphidynamic crystal.

Sliding ferroelectricity is a recently observed polarity existing in two-dimensional materials. However, due to the weak polarization and poor electrical insulation in these materials, existing experimental evidences are indirect and mostly based on nanoscale transport properties or piezoresponse force microscopy. We report the direct observation of sliding ferroelectricity, using a high-quality amphidynamic single crystal (15-crown-5)Cd3Cl6, which possesses a large bandgap and so allows direct measurement of polarization-electric field hysteresis. This coordination polymer is a van der Waals material, which is composed of inorganic stators and organic rotators as determined by X-ray diffraction and NMR characterization. From density functional theory calculations, we find that after freezing the rotators, an electric dipole is generated in each layer driven by the geometric mechanism, while a comparable ferroelectric polarization originates from the interlayer sliding. The net polarization of these two components can be directly measured and manipulated. Our finding provides insight into low-dimensional ferroelectrics, especially control of the synchronous dynamics of rotating molecules and sliding layers in solids.

Distinguishing glutamate and glutamine in in vivo 1 H MRS based on nuclear spin singlet order filtering.

PURPOSE: The signals of glutamate (Glu) and glutamine (Gln) are often significantly overlapped in routine 1 H-MR spectra of human brain in vivo. Selectively probing the signals of Glu and Gln in vivo is very important for the study of the metabolisms in which Glu and Gln are involved. METHODS: The Glu-/Gln- targeted pulse sequences are developed to selectively probe the signals of Glu and Gln. The core part of the Glu-/Gln- targeted pulse sequences lies on the preparation of the nuclear spin singlet orders (SSOs) of the five-spin systems of Glu and Gln. The optimal control method is used to prepare the SSOs of Glu and Gln with high efficiency. RESULTS: The Glu-/Gln- targeted pulse sequences have been applied on phantoms to selectively probe the signals of Glu and Gln. Moreover, in the in vivo experiments, the signals of Glu and Gln in human brains of healthy subjects have been successfully probed separately. CONCLUSION: The developed Glu-/Gln- targeted pulse sequences can be used to distinguish the 1 H-MR signals of Glu and Gln in human brains in vivo. The optimal control method provides an effective way to prepare the SSO of a specific spin system with high efficiency and in turn selectively probe the signals of a targeted molecule.

Performance of Artificial Intelligence-Aided Diagnosis System for Clinically Significant Prostate Cancer with MRI: A Diagnostic Comparison Study.

BACKGROUND: The high level of expertise required for accurate interpretation of prostate MRI. PURPOSE: To develop and test an artificial intelligence (AI) system for diagnosis of clinically significant prostate cancer (CsPC) with MRI. STUDY TYPE: Retrospective. SUBJECTS: One thousand two hundred thirty patients from derivation cohort between Jan 2012 and Oct 2019, and 169 patients from a publicly available data (U-Net: 423 for training/validation and 49 for test and TrumpeNet: 820 for training/validation and 579 for test). FIELD STRENGTH/SEQUENCE: 3.0T/scanners, T2 -weighted imaging (T2 WI), diffusion-weighted imaging, and apparent diffusion coefficient map. ASSESSMENT: Close-loop AI system was trained with an Unet for prostate segmentation and a TrumpetNet for CsPC detection. Performance of AI was tested in 410 internal and 169 external sets against 24 radiologists categorizing into junior, general and subspecialist group. Gleason score >6 was identified as CsPC at pathology. STATISTICAL TESTS: Area under the receiver operating characteristic curve (AUC-ROC); Delong test; Meta-regression I2 analysis. RESULTS: In average, for internal test, AI had lower AUC-ROC than subspecialists (0.85 vs. 0.92, P < 0.05), and was comparable to junior (0.84, P = 0.76) and general group (0.86, P = 0.35). For external test, both AI (0.86) and subspecialist (0.86) had higher AUC than junior (0.80, P < 0.05) and general reader (0.83, P < 0.05). In individual, it revealed moderate diagnostic heterogeneity in 24 readers (Mantel-Haenszel I2  = 56.8%, P < 0.01), and AI outperformed 54.2% (13/24) of readers in summary ROC analysis. In multivariate test, Gleason score, zonal location, PI-RADS score and lesion size significantly impacted the accuracy of AI; while effect of data source, MR device and parameter settings on AI performance is insignificant (P > 0.05). DATA CONCLUSION: Our AI system can match and to some case exceed clinicians for the diagnosis of CsPC with prostate MRI. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Directional vapor transported and water-proof nanofibrous membranes for liquid desiccant dehumidification systems.

The membrane-based liquid desiccant dehumidification system is a newly developed method in the field of air dehumidification. In this study, double-layer nanofibrous membranes (DLNMs) with directional vapor transport and water repellency for liquid dehumidification were fabricated by a simple electrospinning process. Specifically, the combination of thermoplastic polyurethane nanofibrous membrane and polyvinylidene fluoride (PVDF) nanofibrous membrane forms a cone-like structure in DLNMs, resulting in directional vapor transportation. The nanoporous structure and rough surface of PVDF nanofibrous membrane provide waterproof performance for DLNMs. Compare with the commercial membranes, the proposed DLNMs have a significantly higher water vapor permeability coefficient, which is as high as 539.67 g·µm m-2·24 h·Pa. This study not only provides a new route to construct a directional vapor transport and waterproof membrane, but also demonstrates the huge application prospect of the nanofibrous membrane formed by electrospinning in the field of solution dehumidification.

An integrated PK/PD model investigating the impact of tumor size and systemic safety on animal survival in SW1990 pancreatic cancer xenograft.

Survival is one of the most important endpoints in cancer therapy, and parametric survival analysis could comprehensively reveal the overall result of disease progression, drug efficacy, toxicity as well as their interactions. In this study we investigated the efficacy and toxicity of dexamethasone (DEX) combined with gemcitabine (GEM) in pancreatic cancer xenograft. Nude mice bearing SW1990 pancreatic cancer cells derived tumor were treated with DEX (4 mg/kg, i.g.) and GEM (15 mg/kg, i.v.) alone or in combination repeatedly (QD, Q3D, Q7D) until the death of animal or the end of study. Tumor volumes and net body weight (NBW) were assessed every other day. Taking NBW as a systemic safety indicator, an integrated pharmacokinetic/pharmacodynamic (PK/PD) model was developed to quantitatively describe the impact of tumor size and systemic safety on animal survival. The PK/PD models with time course data for tumor size and NBW were established, respectively, in a sequential manner; a parametric time-to-event (TTE) model was also developed based on the longitudinal PK/PD models to describe the survival results of the SW1990 tumor-bearing mice. These models were evaluated and externally validated. Only the mice with good tumor growth inhibition and relatively stable NBW had an improved survival result after DEX and GEM combination therapy, and the simulations based on the parametric TTE model showed that NBW played more important role in animals' survival compared with tumor size. The established model in this study demonstrates that tumor size was not always the most important reason for cancer-related death, and parametric survival analysis together with safety issues was also important in the evaluation of oncology therapies in preclinical studies.

Age-specific transmission dynamics under suppression control measures during SARS-CoV-2 Omicron BA.2 epidemic.

BACKGROUND: From March to June 2022, an Omicron BA.2 epidemic occurred in Shanghai. We aimed to better understand the transmission dynamics and identify age-specific transmission characteristics for the epidemic. METHODS: Data on COVID-19 cases were collected from the Shanghai Municipal Health Commission during the period from 20th February to 1st June. The effective reproductive number (Rt) and transmission distance between cases were calculated. An age-structured SEIR model with social contact patterns was developed to reconstruct the transmission dynamics and evaluate age-specific transmission characteristics. Least square method was used to calibrate the model. Basic reproduction number (R0) was estimated with next generation matrix. RESULTS: R0 of Omicron variant was 7.9 (95% CI: 7.4 to 8.4). With strict interventions, Rt had dropped quickly from 3.6 (95% CI: 2.7 to 4.7) on 4th March to below 1 on 18th April. The mean transmission distance of the Omicron epidemic in Shanghai was 13.4 km (95% CI: 11.1 to 15.8 km), which was threefold longer compared with that of epidemic caused by the wild-type virus in Wuhan, China. The model estimated that there would have been a total 870,845 (95% CI: 815,400 to 926,289) cases for the epidemic from 20th February to 15th June, and 27.7% (95% CI: 24.4% to 30.9%) cases would have been unascertained. People aged 50-59 years had the highest transmission risk 0.216 (95% CI: 0.210 to 0.222), and the highest secondary attack rate (47.62%, 95% CI: 38.71% to 56.53%). CONCLUSIONS: The Omicron variant spread more quickly and widely than other variants and resulted in about one third cases unascertained for the recent outbreak in Shanghai. Prioritizing isolation and screening of people aged 40-59 might suppress the epidemic more effectively. Routine surveillance among people aged 40-59 years could also provide insight into the stage of the epidemic and the timely detection of new variants. TRIAL REGISTRATION: We did not involve clinical trial.

Air pollution control or economic development? Empirical evidence from enterprises with production restrictions.

Production restriction is an environmental regulation adopted in China to curb the air pollution of industrial enterprises. Frequent production restrictions may cause economic losses for enterprises and further hinder their green transformation. Polluting enterprises are faced with the dilemma of choosing environmental protection or economic development. Using panel data on industrial enterprises in China from 2016 to 2019, this paper evaluates the impact of production restrictions on both enterprises' environmental and economic performance with regression models. The results show that production restrictions significantly drop the concentrations of SO2 and NOx emitted from polluting enterprises. Meanwhile, production restrictions have significant negative effects on operating income, financial expenses, net profit, and environmental protection investment. The mechanism analysis reveals that production restrictions mitigate air pollutant concentrations by increasing the number of green patents and improving total factor productivity, which also verifies the Porter hypothesis. However, there is a masking mediating effect of environmental investment, which indicates that the reduction of environmental investment hinders the enterprise's efforts to control air pollution. In addition, heterogeneous analysis shows that the economic shock on microenterprises is larger than that on small enterprises. Implementing production restrictions for microenterprises may be a way to eliminate their backwards production capacity.

Preparation and Property Characterization of Sm2EuSbO7/ZnBiSbO5 Heterojunction Photocatalyst for Photodegradation of Parathion Methyl under Visible Light Irradiation.

An unprecedented photocatalyst, Sm2EuSbO7, was successfully fabricated in this paper, through a high-temperature solid-state calcination method, which represented its first ever synthesis. Additionally, using the solvothermal method, the Sm2EuSbO7/ZnBiSbO5 heterojunction photocatalyst (SZHP) was fabricated, marking its debut in this study. XRD analysis confirmed that both Sm2EuSbO7 and ZnBiSbO5 exhibited pyrochlore-type crystal structures with a cubic lattice, belonging to the Fd3m space group. The crystal cell parameter was determined to be 10.5682 Å or 10.2943 Å for Sm2EuSbO7 or ZnBiSbO5, respectively. The band gap width measured for Sm2EuSbO7 or ZnBiSbO5 was 2.73 eV or 2.61 eV, respectively. Under visible light irradiation for 150 min (VLTI-150 min), SZHP exhibited remarkable photocatalytic activity, achieving 100% removal of parathion methyl (PM) concentration and 99.45% removal of total organic carbon (TOC) concentration. The kinetic constant (k) for PM degradation and visible light illumination treatment was determined to be 0.0206 min-1, with a similar constant k of 0.0202 min-1 observed for TOC degradation. Remarkably, SZHP exhibited superior PM removal rates compared with Sm2EuSbO7, ZnBiSbO5, or N-doped TiO2 photocatalyst, accompanied by removal rates 1.09 times, 1.20 times, or 2.38 times higher, respectively. Furthermore, the study investigated the oxidizing capability of free radicals through the use of trapping agents. The results showed that hydroxyl radicals had the strongest oxidative capability, followed by superoxide anions and holes. These findings provide a solid scientific foundation for future research and development of efficient heterojunction compound catalysts.

Association of tumor mutational burden with genomic alterations in Chinese urothelial carcinoma.

The tumor mutational burden (TMB) calculated by whole-exome sequencing (WES) is a promising biomarker for the response to immune checkpoint inhibition (ICIs) in solid tumors. However, WES is not feasible in the routine clinical setting. In addition, the characteristics of the TMB in Chinese urothelial carcinoma (UC) are unclear. The aim of this study was to demonstrate the reliability of an Acornmed 808 panel and analyze the characteristics of the TMB in Chinese UC. An Acornmed 808 panel was designed and virtually validated using UC data from the cancer genome atlas (TCGA). Comprehensive analysis of sequencing and clinical data was performed to explore the characteristics of the TMB for 143 Chinese UC patients. Compared to the TMB calculated with random 808-, 500-, and 250-gene panels, the TMB calculated with the Acornmed 808 panel was closer to that calculated by WES. There were marked disparities in the mutational landscape and TMB between Chinese and TCGA UC data. The TMB was negatively associated with copy number variation (CNV). In contrast, the TMB was positive correlation with numbers of mutated DDR genes. Exposure to aristolochic acid signature was observed only in the TMB-high groups. The Acornmed 808 panel is a clinically practical method to assess the TMB. The TMB was associated with the DDR gene status and CNV counts and might be a biomarker for further stratification of UC patients. The study suggested that patients with high TMB may have a unique carcinogenic mechanism.

Glutathione-Responsive Heterogeneous Metal-Organic Framework Hybrids for Photodynamic-Gene Synergetic Cell Apoptosis.

A core-shell heterogeneous metal-organic framework (MOF) hybrid is sequentially designed by a photosensitized porous coordination network (PCN)-typed MOF as core and Cu2+ -centered zeolitic imidazolate framework (ZIF-67) as shell encapsulating cyanine 3-labelled siRNA. The heterogeneous MOF hybrid realized stimulus-responsive photodynamic therapy (PDT) and controllable siRNA delivery through 1 O2 -assistant endosomal escape for imaging-guided photodynamic-gene synergetic theranostics.

Prognostic value of CSN5 in patients with digestive system cancers: a systematic review and meta-analysis.

BACKGROUND: Despite the understanding of the COP9 signalosome subunit 5 (CSN5) in tumor genesis, there is no conclusive evidence on its value to predict the survival and prognosis of digestive system tumor patients. Hence this study aimed to evaluate the impact of CSN5 levels on the survival and clinicopathological parameters of digestive system neoplasm patients. METHODS: First, a comprehensive search was conducted in four databases. We utilized the Hazard Ratio (HR) with a 95% confidence interval (CI) to evaluate the prognostic value of CSN5 for the overall survival (OS) and recurrence-free survival (RFS) of patients. Then, we estimated the connection between CSN5 and the clinicopathological parameters based on the Odds Ratio (OR) with the corresponding 95% CI. RESULTS: This meta-analysis included 22 studies and 2193 patients diagnosed with digestive system tumors. High expression of CSN5 was correlated to poorer OS (HR = 2.28, 95% CI: 1.71-3.03; p < 0.00001). Additionally, high CSN5 levels were correlated with worse invasion depth (OR = 0.49, 95% CI: 0.25-0.96, p = 0.04), positive lymphatic metastasis (OR = 0.28, 95% CI: 0.16-0.47, p = 0.00001), positive distant metastasis (OR = 0.32, 95% CI: 0.13-0.76, p = 0.01) and poorer differentiation degree (OR = 0.34, 95% CI: 0.19-0.60, p = 0.0003). However, we did not detect a correlation between CSN5 expression and age, gender, tumor stage, tumor size or vascular invasion. Furthermore, no significant publication bias was detected. CONCLUSION: This meta-analysis demonstrated that the overexpression of CSN5 level might foresee poorer OS in digestive system cancer patients. Additionally, CSN5 levels might be related to the prognosis of digestive system tumors.

ITGB4 deficiency induces DNA damage by downregulating HDAC1 in airway epithelial cells under stress stimulation.

BACKGROUND: DNA damage in airway epithelia under exogenous disruptors can trigger various pulmonary diseases. Integrin beta 4 (ITGB4) is a structural adhesion molecule, which is indicated to regulate the process of DNA damage in airway epithelia for its unique long cytoplasmic domain subunit. METHODS: The expression level of ITGB4 and the degree of DNA damage were observed in the house dust mite (HDM)-stressed model and ozone-challenged model, respectively. Besides, ITGB4 conditional knockout mice and ITGB4-deficient airway epithelial cells were constructed to observe the influence of ITGB4 deficiency on DNA damage. Furthermore, the influence of ITGB4 deficiency on HDAC1 expression in airway epithelia was determined under stress stimulation. Finally, corresponding intervention strategies were carried out to verify the involvement of the ITGB4-mediated HDAC1 pathway in DNA damage of airway epithelial cells. RESULTS: HDM stress and ozone challenge reduced the expression of ITGB4, which is accompanied by the increased expression of 8-oxoG and γ-H2AX both in vivo and in vitro. Moreover, ITGB4 deficiency in airway epithelia aggravates the degree of DNA damage under HDM stimulation and ozone stress, respectively. Furthermore, ITGB4 deficiency downregulated the expression of HDAC1 during DNA damage, and restoring HDAC1 can reverse the enhanced DNA damage in airway epithelial cells after exogenous stress. CONCLUSIONS: This study confirmed the involvement of ITGB4 in the regulation of DNA damage through mediating HDAC1 in airway epithelial cells under exogenous stress. These results supply some useful insights into the mechanism of DNA damage in airway epithelial cells, which would provide possible targets for early prediction and intervention of pulmonary diseases.