Metabolic reprogramming based on RNA sequencing of gemcitabine-resistant cells reveals the FASN gene as a therapeutic for bladder cancer.

Bladder cancer (BLCA) is the most frequent malignant tumor of the genitourinary system. Postoperative chemotherapy drug perfusion and chemotherapy are important means for the treatment of BLCA. However, once drug resistance occurs, BLCA develops rapidly after recurrence. BLCA cells rely on unique metabolic rewriting to maintain their growth and proliferation. However, the relationship between the metabolic pattern changes and drug resistance in BLCA is unclear. At present, this problem lacks systematic research. In our research, we identified and analyzed resistance- and metabolism-related differentially expressed genes (RM-DEGs) based on RNA sequencing of a gemcitabine-resistant BLCA cell line and metabolic-related genes (MRGs). Then, we established a drug resistance- and metabolism-related model (RM-RM) through regression analysis to predict the overall survival of BLCA. We also confirmed that RM-RM had a significant correlation with tumor metabolism, gene mutations, tumor microenvironment, and adverse drug reactions. Patients with a high drug resistance- and metabolism-related risk score (RM-RS) showed more active lipid synthesis than those with a low RM-RS. Further in vitro and in vivo studies were implemented using Fatty Acid Synthase (FASN), a representative gene, which promotes gemcitabine resistance, and its inhibitor (TVB-3166) that can reverse this resistance effect.

Cellular senescence and metabolic reprogramming model based on bulk/single-cell RNA sequencing reveals PTGER4 as a therapeutic target for ccRCC.

Clear cell renal cell carcinoma (ccRCC) is the prevailing histological subtype of renal cell carcinoma and has unique metabolic reprogramming during its occurrence and development. Cell senescence is one of the newly identified tumor characteristics. However, there is a dearth of methodical and all-encompassing investigations regarding the correlation between the broad-ranging alterations in metabolic processes associated with aging and ccRCC. We utilized a range of analytical methodologies, such as protein‒protein interaction network analysis and least absolute shrinkage and selection operator (LASSO) regression analysis, to form and validate a risk score model known as the senescence-metabolism-related risk model (SeMRM). Our study demonstrated that SeMRM could more precisely predict the OS of ccRCC patients than the clinical prognostic markers in use. By utilizing two distinct datasets of ccRCC, ICGC-KIRC (the International Cancer Genome Consortium) and GSE29609, as well as a single-cell dataset (GSE156632) and real patient clinical information, and further confirmed the relationship between the senescence-metabolism-related risk score (SeMRS) and ccRCC patient progression. It is worth noting that patients who were classified into different subgroups based on the SeMRS exhibited notable variations in metabolic activity, immune microenvironment, immune cell type transformation, mutant landscape, and drug responsiveness. We also demonstrated that PTGER4, a key gene in SeMRM, regulated ccRCC cell proliferation, lipid levels and the cell cycle in vivo and in vitro. Together, the utilization of SeMRM has the potential to function as a dependable clinical characteristic to increase the accuracy of prognostic assessment for patients diagnosed with ccRCC, thereby facilitating the selection of suitable treatment strategies.

Tailoring Charge Flow in Carbon-Defective Cu-MOF with Pd Nanoparticles: A Boost for Visible Light Organic Photoelectrochemical Transistor in Bioanalysis.

The photoactive material was of significant importance in organic photoelectrochemical transistor (OPECT) bioanalysis as it influences the photoinduced voltage and the µC* product, resulting in a varying sensor sensitivity. The utilization of metal-organic frameworks (MOFs) as photoactive materials in OPECT analysis is promising, yet it remains a grand challenge due to the inherently narrow light absorption range and high electron-hole recombination rate. Herein, Pd NPs were encapsulated as electron acceptors into the Cu-MOF using a double-solvent method, followed by pyrolysis at the proper temperature. After pyrolysis, Cu-MOF transformed into a carbon defect-rich composite of CuO and Cu2O while retaining its high porosity and structural morphology. The resulting carbon defect-rich pyrolysis Cu-MOF (p-Cu-MOF) served as an active support, facilitating the separation of electrons and holes. The photoelectrons trigger the electron transfer of adjacent active metal components and the formation of a Schottky junction between Pd and the MOFs. This effect induces the electron donation from the MOFs. Moreover, Pd/pyrolysis Cu-MOF exhibits significantly higher visible light absorption, better water stability, and higher electrical conductivity compared to Cu-MOF and Pd/Cu-MOF. An OPECT sensor was fabricated by utilizing Pd/p-Cu-MOF as the photoactive material and poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) as the channel material on an integrated laser-etched FTO. The aptamer was used as the recognition element, enabling sensitive and efficient detection of residual isocarbophos.

Risk factors for repeated percutaneous transluminal angioplasty of hemodialysis vascular access after initial intervention.

BACKGROUND/AIMS: Percutaneous transluminal angioplasty (PTA) is a significant intervention to deal with occlusion and stenosis of vascular access. The study aimed to explore the risk factors of repeated PTA (re-PTA) after the initial intervention in patients undergoing hemodialysis. METHODS: This retrospective study included 180 patients who underwent successful PTA for the first time between March 2016 and December 2020. Information on demographic, clinical, anatomical, and medication variables was collected. Survival curves were plotted using Kaplan-Meier analysis and the risk factors associated with re-PTA were analyzed using univariate and multivariate Cox proportional hazards analyses. RESULTS: The primary clinical patency rates at 6, 12, and 24 months after PTA were found to be 85.2%, 70.7%, and 58.6%, respectively. The univariate Cox proportion hazards analysis revealed the association of non-antiplatelet agents (HR 2.368 95% CI 1.351 to 4.150, p = .003) and arteriovenous graft (AVG) (HR 2.096 95% CI 1.147 to 3.831, p = .016) with re-PTA. However, only non-antiplatelet therapy showed statistical significance (HR 2.368 95% CI 1.351 to 4.150, p = .003) in multivariate Cox proportional hazards analysis. CONCLUSIONS: Among the patients undergoing hemodialysis, the use of antiplatelet agents was associated with a lower risk of re-PTA. Therefore, the use of antiplatelet drugs may reduce the rates of re-PTA and help in maintaining the patency of vascular access.

Target-Induced Photocurrent-Polarity-Switching PEC Sensing Platform Based on In Situ Generation of Oxygen Vacancy-Modulated Energy Band Structures.

The polarity of the photocurrent can be modulated by tunable bipolar photoelectrochemical (PEC) behavior, which is anticipated to address the issues of high background signal caused by traditional unidirectional increasing/decreasing response and false-positive/false-negative problems. Here, a new approach is suggested for the first time, which employs a target-induced enzyme-catalyzed reaction and in situ oxygen vacancy (OV) generation to achieve heterojunction photocurrent switching for highly sensitive detection of alkaline phosphatase (ALP). Among them, the ALP can catalyze the decomposition of ascorbic acid phosphate to produce ascorbic acid, which not only acts as an electron donor to change the redox environment but also acts as a reducing agent to introduce OVs into BiOBr semiconductors in cooperation with illumination. The introduction of vacancies can effectively modulate the energy band structure of BiOBr, while with the change of redox conditions, the transfer path of photogenerated carriers is changed, thus realizing the switching of photocurrents, which leads to its use in the construction of a negative-background anti-interference PEC sensing platform, achieving a wide linear range from 0.005 to 500 U·L-1 with a low detection limit of 0.0017 U·L-1. In conclusion, the photocurrent switching operation of this system is jointly regulated by chemistry, optics, and carrier motion, which provides a new idea for the construction of a PEC sensing platform based on photocurrent polarity switching.

Biomimetic Two-Dimensional Vermiculite Nanofluidic Membranes for Stable Salinity-Gradient Energy Conversion.

Aligned ion transport in the nanofluidic membrane is promising for efficient salinity-gradient energy conversion, while remaining rather challenging due to relatively inadequate mass transport and long-time durability. In this work, wet-chemically exfoliated and negatively charged vermiculite lamellas are readily restacked into free-standing membranes with massive arrays of nanochannels and a three-dimensional interface. The resulting vermiculite nanofluidic membranes possess excellent stability against harsh conditions including a wide pH range and high temperature and exhibit a different ion transport behavior from the macroscopic one due to the surface-charge-governed conductivity. The ionic conductivity is several orders of magnitude higher than that of the native solution at low concentrations. Moreover, the negatively charged lamellas create a space charge zone, making the nanofluidic membrane capable of coupling surface charge and space charge in confinement for salinity-gradient energy conversion from seawater and freshwater. Compared with other layered materials, the vermiculite-derived membranes have distinct advantages such as low cost, facile fabrication, and high stability. This work provides a new idea for designing nanofluidic membranes from phyllosilicate minerals, which offers opportunities for manufacturing nanofluidic devices.

Statins and risk of venous thromboembolic diseases: A two-sample mendelian randomization study.

BACKGROUND AND AIMS: In observational studies, statins have been suggested to have protective effects on venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE). To this aim, we performed a two-sample mendelian randomization (MR) analysis to determine whether these associations were causal. METHODS AND RESULTS: Data on the single nucleotide polymorphisms (SNPs) related to statin medication were obtained from the FinnGen study, and data for VTE, PE and DVT of lower extremities (LEDVT) were from the UK Biobank study, respectively. Inverse variance weighted (IVW) method was used as the principal analysis of MR, and sensitivity analysis was performed to detect horizontal pleiotropy and heterogeneity. MR estimates showed an inverse causal association between statin medication and the risk of VTE (odds ratio [OR]: 0.999, 95% CI: 0.998-1.000, P = 0.004), PE (OR: 0.999, 95% CI: 0.999-1.000, P = 0.011) and LEDVT (OR: 0.999, 95% CI: 0.999-1.000, P = 0.008). CONCLUSION: Our findings provide direct evidence that statins might decrease the risk of VTE, PE and LEDVT in agreement with observational studies. The specific mechanism of statin therapy for venous thromboembolism needs to be further studied.

Microdosimetric Analysis for Boron Neutron Capture Therapy via Monte Carlo Track Structure Simulation with Modified Lithium Cross-sections.

Boron neutron capture therapy (BNCT) is a cellular-level hadron therapy achieving therapeutic effects via the synergistic action of multiple particles, including Lithium, alpha, proton, and photon. However, evaluating the relative biological effectiveness (RBE) in BNCT remains challenging. In this research, we performed a microdosimetric calculation for BNCT using the Monte Carlo track structure (MCTS) simulation toolkit, TOPAS-nBio. This paper reports the first attempt to derive the ionization cross-sections of low-energy (>0.025 MeV/u) Lithium for MCTS simulation based on the effective charge cross-section scalation method and phenomenological double-parameter modification. The fitting parameters λ1=1.101,λ2=3.486 were determined to reproduce the range and stopping power data from the ICRU report 73. Besides, the lineal energy spectra of charged particles in BNCT were calculated, and the influence of sensitive volume (SV) size was discussed. Condensed history simulation obtained similar results with MCTS when using Micron-SV while overestimating the lineal energy when using Nano-SV. Furthermore, we found that the microscopic boron distribution can significantly affect the lineal energy for Lithium, while the effect for alpha is minimal. Similar results to the published data by PHITS simulation were observed for the compound particles and monoenergetic protons when using micron-SV. Spectra with nano-SV reflected that the different track densities and absorbed doses in the nucleus together result in the dramatic difference in the macroscopic biological response of BPA and BSH. This work and the developed methodology could impact the research fields in BNCT where understanding radiation effects is crucial, such as the treatment planning system, source evaluation, and new boron drug development.

Urea-Mediated Monoliths Made of Nitrogen-Enriched Mesoporous Carbon Nanosheets for High-Performance Aqueous Zinc Ion Hybrid Capacitors.

Aqueous zinc ion hybrid capacitors (aZHCs) are of great potential for large-scale energy storage and flexible wearable devices, of which the specific capacity and energy density need to be further enhanced for practical applications. Herein, a urea-mediated foaming strategy is reported for the efficient synthesis of monoliths consisting of nitrogen-enriched mesoporous carbon nanosheets (NPCNs) by prefoaming drying a solution made of polyvinylpyrrolidone, zinc nitrate, and urea at low temperatures, foaming and annealing at high temperatures, and subsequent acid etching. NPCNs have a large lateral size of ≈40 µm, thin thickness of ≈55 nm, abundant micropores and mesopores (≈3.8 nm), and a high N-doping value of 9.7 at.%. The NPCNs as the cathode in aZHCs provide abundant zinc storage sites involving both physical and chemical adsorption/desorption of Zn2+  ions, and deliver high specific capacities of 262 and 115 mAh g-1 at 0.2 and 10 A g-1 , and a remarkable areal capacity of ≈0.5 mAh cm-2  with a mass loading of 5.3 mg cm-2 , outperforming most carbon cathodes reported thus far. Moreover, safe and flexible NPCNs based quasi-solid-state devices are fabricated, which can withstand drilling and mechanical bending, suggesting their potential applications in wearable devices.

Production of fermented spicy rabbit meat using Lactobacillus paracasei.

Lactobacillus paracasei was used to produce fermented spicy rabbit meat. A series of indexes were determined, including pH value, free amino acid content, true protein content, texture, microstructure and the volatile compounds of fermented spicy rabbit meat and unfermented spicy rabbit meat. The results showed that Lactobacillus paracasei could reduce the pH value of spicy rabbit meat (from 6.85 to 4.65), could degrade the proteins of spicy rabbit meat, could increase the content of free amino acids (from 205.1 mg/100 g to 505.6 mg/100 g), and could improve its textural properties and organoleptic quality of the spicy rabbit meat. The microstructure of the fermented spicy rabbit meat and unfermented spicy rabbit meat was observed by scanning electron microscope. The results showed that the microstructure of the fermented spicy rabbit meat changed obviously, the arrangement of muscle fibers was loose or even seriously broken, and many small pieces were formed, which indicated that the fermentation could improve the tenderness of the rabbit meat. The kinds of volatile flavor compounds after fermentation were increased from 14 to 40 as estimated by solid phase microextraction and GC-MS. Therefore, utilization of microbial fermentation technology can improve the quality, texture, tenderness and flavor of spicy rabbit meat, and enhance the digestion and absorption capacity.

A Gold(I) Complex Containing an Oleanolic Acid Derivative as a Potential Anti-Ovarian-Cancer Agent by Inhibiting TrxR and Activating ROS-Mediated ERS.

Many cancer cells critically rely on antioxidant systems for cell survival and are vulnerable to further oxidative impairment triggered by agents generating reactive oxygen species (ROS). Therefore, the classical design and development of inhibitors that target antioxidant defense enzymes such as thioredoxin reductase (TrxR) can be a promising anticancer strategy. Herein, it is shown that a gold(I) complex containing an oleanolic acid derivative (4 b) induces apoptosis of ovarian cancer A2780 cells by activating endoplasmic reticulum stress (ERS). It can inhibit TrxR enzyme activity to elevate ROS, mediate ERS and mitochondrial dysfunction, and finally leads to cell cycle arrest and apoptosis of A2780 cells. Notably, this complex inhibits A2780 xenograft tumor growth accompanied by increased ERS level and decreased TrxR activity in tumor tissues.

Unsupervised multi-granular Chinese word segmentation and term discovery via graph partition.

OBJECTIVE: This study aims at realizing unsupervised term discovery in Chinese electronic health records (EHRs) by using the word segmentation technique. The existing supervised algorithms do not perform satisfactorily in the case of EHRs, as annotated medical data are scarce. We propose an unsupervised segmentation method (GTS) based on the graph partition principle, whose multi-granular segmentation capability can help realize efficient term discovery. METHODS: A sentence is converted to an undirected graph, with the edge weights based on n-gram statistics, and ratio cut is used to split the sentence into words. The graph partition is solved efficiently via dynamic programming, and multi-granularity is realized by setting different partition numbers. A BERT-based discriminator is trained using generated samples to verify the correctness of the word boundaries. The words that are not recorded in existing dictionaries are retained as potential medical terms. RESULTS: We compared the GTS approach with mature segmentation systems for both word segmentation and term discovery. MD students manually segmented Chinese EHRs at fine and coarse granularity levels and reviewed the term discovery results. The proposed unsupervised method outperformed all the competing algorithms in the word segmentation task. In term discovery, GTS outperformed the best baseline by 17 percentage points (a 47% relative percentage of increment) on F1-score. CONCLUSION: In the absence of annotated training data, the graph partition technique can effectively use the corpus statistics and even expert knowledge to realize unsupervised word segmentation of EHRs. Multi-granular segmentation can be used to provide potential medical terms of various lengths with high accuracy.

Outcomes of primary membranous nephropathy based on serum anti-phospholipase A2 receptor antibodies and glomerular phospholipase A2 receptor antigen status: a retrospective cohort study.

INTRODUCTION: Primary membranous nephropathy (PMN) is associated with the anti-phospholipase A2 receptor (anti-PLA2R) antibody in 70% of cases. Some anti-PLA2R-negative patients have the PLA2R antigen in renal tissue. This study examined the prognosis of patients with PMN according to their serum anti-PLA2R antibody (SAb) and glomerular PLA2R antigen (GAg) status. METHODS: Patients diagnosed with PMN were included retrospectively. Patients were grouped according to their PLA2R status into the SAb-/GAg-, SAb-/GAg+, and SAb+/GAg + groups. Baseline data, renal biopsy results, treatment, and clinical data were compared among the groups. Cox univariable and multivariable analyses examined the factors related to complete remission (CR). RESULTS: A total of 114 patients were enrolled; 10 (9%) in the SAb-/GAg-, 23 (20%) in the SAb-/GAg+, and 81 (71%) in the SAb+/GAg+ groups. Cumulative CR rate showed a significant difference between the SAb-/GAg - and SAb+/GAg+ groups (log-rank p = 0.003). The multivariable Cox proportional hazard analysis showed that age (HR = 0.968; 95%CI = 0.946-0.990; p = 0.005), SAb+/GAg+ versus SAb-/GAg- (HR = 0.387; 95%CI = 0.190-0.788; p = 0.009), SAb-/GAg+ versus SAb-/GAg- (HR = 0.398; 95%CI = 0.169, 0.939; p = 0.035), total renal chronicity score ≥2 (HR = 0.461, 95%CI: 0.277-0.766, p = 0.003), and IgA deposition (HR = 2.596; 95%CI = 1.227-5.492; p = 0.013) were all independently related (p < 0.05) to CR. CONCLUSIONS: The SAb and GAg status was an indicator of PMN prognosis. The patients with SAb-/GAg - had an increased likelihood of achieving CR than those with SAb-/GAg+ and SAb+/GAg+.

A Rare Experience of Infective Residual Sheath in the Wall of the Innominate Vein after Extraction of Implantable-Defibrillators.

BACKGROUND: Cardiac device-related infective endocarditis is an uncommon but potentially fatal complication. Therefore, cardiac devices should be removed as soon as a device-related infection is suspected. CASE REPORT: A 56-year-old male with a history of arrhythmogenic right ventricular dysplasia with implantable cardioverter-defibrillators (ICDs) 7 years earlier and re-implantation of ICDs due to dysfunction 18 months ago presented with erosion of the ICD pocket with Pseudomonas bacteremia. For the past year, only multiple wound debridements were performed. Accordingly, we performed debridement and removal of the generator during this admission; however, bacteremia still persisted. Using transesophageal echocardiography, we detected vegetation on the pacing leads and tricuspid valve in the right atrium. We performed thoracotomy with tricuspid valve repair and pacing wire removal. However, anterior chest pain and refractory bacteremia occurred 3 months later after discharge, and an infectious foreign body in the wall of the innominate vein was detected using chest computer tomography. Thoracotomy was again performed for resection of the innominate vein with the infection source. Postoperative recovery was good, with no systemic infection or bacteremia. CONCLUSIONS: Pacing lead extraction is a common procedure following cardiac rhythm management device-related infection. However, residual foreign body-related bacteremia should be suspected in cases with fever of unknown origin after primary surgery. Preserving the innominate vein with patch repair is a feasible option. However, a postoperative 4-week course of antibiotics is recommended.

Incidence and Survival of Patients With Malignant Primary Spinal Cord Tumors: A Population-Based Analysis.

OBJECTIVE: Epidemiological studies on spinal cord tumors are rare, and studies on primary intramedullary tumors are even rarer. The incidence and survival of patients with primary intramedullary spinal cord tumors have not been well documented. We aimed to study the incidence and survival of patients with primary spinal cord malignant and borderline malignant tumors based on data from the Surveillance, Epidemiology, and End Results (SEER) database and provide information for revealing the epidemiology and exploring the prognosis of patients with primary intramedullary tumors. METHODS: Patients in the SEER database with microscopically diagnosed malignant and borderline malignant primary spinal cord tumors from 2000 and 2019 were included in this study. We analyzed the distribution of patients according to the demographic and clinical characteristics. Then, we extracted the incidence rate and 5-year relative survival for the whole cohort and different subgroups of the cohort. Finally, multivariate Cox proportional hazards models were used to analyze the independent prognostic factors associated with overall survival. RESULTS: A total of 5,211 patients with malignant and borderline malignant primary spinal cord tumors were included in this cohort study. Ependymoma, astrocytoma (including oligodendrogliomas and glioblastoma), lymphoma and hemangioblastoma were the most common pathological types. The age-adjusted incidence rates of primary spinal cord ependymoma was 0.18 per 100,000. The incidence rate for females was significantly lower than that for males. The incidence rate was highest in Caucasian. The incidence rate of ependymoma was significantly higher than that of other pathological types. The incidence of astrocytoma was highest among people aged 0-19 years, the incidence of ependymoma was highest among people aged 40-59 years, and the incidence of lymphoma was highest among people aged 60 years or older. The 5-year observed survival and relative survival rates for the whole cohort were 82.80% and 86.00%, respectively. Patients diagnosed with ependymoma had significantly better survival than their counterparts. We also found the impact of surgery and chemotherapy on the prognosis of patients with different tumors varies a lot. CONCLUSION: We conducted a population-based analysis of malignant and borderline malignant primary spinal cord tumors with the aim of revealing the epidemiology and survival of patients with primary intramedullary spinal cord tumors. Despite some shortcomings, this study provides valuable information to help us better understand the epidemiological characteristics of primary intramedullary spinal cord tumors.

Synergistic effect of surface metal vacancies and Schottky junction on high-transconductance organic photoelectrochemical transistor aptasensing.

The synergistic effect between surface metal vacancies and a Schottky junction on enhanced transconductance, and the gating effect of an organic photoelectrochemical transistor was reported.

DeepMicroClass sorts metagenomic contigs into prokaryotes, eukaryotes and viruses.

Sequence classification facilitates a fundamental understanding of the structure of microbial communities. Binary metagenomic sequence classifiers are insufficient because environmental metagenomes are typically derived from multiple sequence sources. Here we introduce a deep-learning based sequence classifier, DeepMicroClass, that classifies metagenomic contigs into five sequence classes, i.e. viruses infecting prokaryotic or eukaryotic hosts, eukaryotic or prokaryotic chromosomes, and prokaryotic plasmids. DeepMicroClass achieved high performance for all sequence classes at various tested sequence lengths ranging from 500 bp to 100 kbps. By benchmarking on a synthetic dataset with variable sequence class composition, we showed that DeepMicroClass obtained better performance for eukaryotic, plasmid and viral contig classification than other state-of-the-art predictors. DeepMicroClass achieved comparable performance on viral sequence classification with geNomad and VirSorter2 when benchmarked on the CAMI II marine dataset. Using a coastal daily time-series metagenomic dataset as a case study, we showed that microbial eukaryotes and prokaryotic viruses are integral to microbial communities. By analyzing monthly metagenomes collected at HOT and BATS, we found relatively higher viral read proportions in the subsurface layer in late summer, consistent with the seasonal viral infection patterns prevalent in these areas. We expect DeepMicroClass will promote metagenomic studies of under-appreciated sequence types.

A terbium(III) complex-based time-resolved luminescent probe for selenocysteine as an inhibitor of selenoproteins.

A terbium(III) complex-based time-resolved luminescence probe for selenocysteine can inhibit selenoprotein activity via a selenolate-triggered cleavage reaction of sulfonamide bonds in living cells.

Molecular engineering of AIE-active boron clustoluminogens for enhanced boron neutron capture therapy.

The development of boron delivery agents bearing an imaging capability is crucial for boron neutron capture therapy (BNCT), yet it has been rarely explored. Here we present a new type of boron delivery agent that integrates aggregation-induced emission (AIE)-active imaging and a carborane cluster for the first time. In doing so, the new boron delivery agents have been rationally designed by incorporating a high boron content unit of a carborane cluster, an erlotinib targeting unit towards lung cancer cells, and a donor-acceptor type AIE unit bearing naphthalimide. The new boron delivery agents demonstrate both excellent AIE properties for imaging purposes and highly selective accumulation in tumors. For example, at a boron delivery agent dose of 15 mg kg-1, the boron amount reaches over 20 µg g-1, and both tumor/blood (T/B) and tumor/normal cell (T/N) ratios reach 20-30 times higher than those required by BNCT. The neutron irradiation experiments demonstrate highly efficient tumor growth suppression without any observable physical tissue damage and abnormal behavior in vivo. This study not only expands the application scopes of both AIE-active molecules and boron clusters, but also provides a new molecular engineering strategy for a deep-penetrating cancer therapeutic protocol based on BNCT.

CHRNA9 as a New Prognostic Marker and Potential Therapeutic Target in Glioma.

Background: The nicotinic acetylcholine receptor (nAChR) subunit alpha-9 (CHRNA9) is a unique cholinergic receptor, which is involved in tumor proliferation, apoptosis, metastasis and chemotherapy resistance. However, the correlation between the expression level of CHRNA9 in glioma and the clinical features and prognosis of glioma patients has not been clarified. The aim of this study was to verify the expression level of CHRNA9 in glioma and its effect on prognosis by bioinformatics methods. Methods: The RNA-seq data of glioma and normal samples were obtained from the TCGA and GTEx databases. Bioinformatics methods were utilized to analyze the differential expression of CHRNA9 between tumor samples and normal samples. The potential association between CHRNA9 and the clinicopathological features of glioma patients was also investigated. The Kaplan-Meier method and Cox regression were utilized to analyze the relationship between CHRNA9 expression level and survival time and prognostic value of glioma patients. Enrichment analysis was applied to predict gene function and signaling pathways associated with CHRNA9. Experimental verification was performed using tumor tissues and paracancerous tissues from glioma patients. Results: The results of bioinformatics analysis showed that the expression of CHRNA9 was increased in glioma tissues, correlating with poor prognosis and reduced patient survival time. Enrichment analysis suggested that CHRNA9 may interact with the JAK/STAT pathway. CHRNA9 was also found to be abnormally expressed in various other tumors and associated with the expression levels of numerous immune checkpoints in glioma. The findings from the analysis of clinical samples revealed that the expression levels of both mRNA and protein of CHRNA9 in glioma tissues were higher than those in paracancerous tissues. Similarly, the mRNA expression levels of STAT3, IL-6, and TNF-α, which are crucial factors in the STAT3 pathway, were elevated in glioma tissues compared to paracancerous tissues. Conclusion: CHRNA9 is a potential prognostic marker and immunotherapy target for glioma, with its mechanism of action potentially linked to the STAT3 pathway.