Lanthanum-based dendritic mesoporous nanoplatform for tumor microenvironment activating synergistic anti-glioma efficacy.

Lanthanum (La)-based nanotherapeutics are therapeutically advantageous due to cytoplasmic oxygen species (ROS) levels for mediating intrinsic and extrinsic tumor cell apoptosis. While they have not been extensively explored for their potential to suppress malignancies in vivo. Correspondingly, we have formulated a unique lanthanum nanocarrier with high specific surface area, dendritic-divergent mesopores, importantly, exposing more active lanthanum sites. After surface PEGlytion and ICG loading in mesoporous channels, this fantastic nanoplatform can efficaciously enrich in malignant glioblastoma regions. Meaningfully, it can be sensitively dissociated for La ions release under weak acid (pH = 6.5) tumor microenvironment. Upon 808 nm light irradiation, high light-heat conversion efficiency is further proved, then this satisfied thermal in the tumor site progressively enhances ROS production by La ions. Owing to the synergistic oxidative therapy and photothermal therapy of our dendritic La nanoplatform, glioblastoma is efficaciously and synergistically prevented both in vitro and in vivo. All outcomes highlight the therapeutic potency of La based nanoplatform with radial mesopores to treat malignant cancer in vivo and encourage future translational exploration.

Engineering PEG10assembled endogenous virus-like particles with genetically encoded neoantigen peptides for cancer vaccination.

Tumor neoantigen peptide vaccines hold potential for boosting cancer immunotherapy, yet efficiently co-delivering peptides and adjuvants to antigen-presenting cells in vivo remains challenging. Virus-like particle (VLP), which is a kind of multiprotein structure organized as virus, can deliver therapeutic substances into cells and stimulate immune response. However, the weak targeted delivery of VLP in vivo and its susceptibility to neutralization by antibodies hinder their clinical applications. Here, we first designed a novel protein carrier using the mammalian-derived capsid protein PEG10, which can self-assemble into endogenous VLP (eVLP) with high protein loading and transfection efficiency. Then, an engineered tumor vaccine, named ePAC, was developed by packaging genetically encoded neoantigen into eVLP with further modification of CpG-ODN on its surface to serve as an adjuvant and targeting unit to dendritic cells (DCs). Significantly, ePAC can efficiently target and transport neoantigens to DCs, and promote DCs maturation to induce neoantigen-specific T cells. Moreover, in mouse orthotopic liver cancer and humanized mouse tumor models, ePAC combined with anti-TIM-3 exhibited remarkable antitumor efficacy. Overall, these results support that ePAC could be safely utilized as cancer vaccines for antitumor therapy, showing significant potential for clinical translation.

Mouse testicular macrophages can independently produce testosterone and are regulated by Cebpb.

BACKGROUND: Testicular macrophages (TM) have long been recognized for their role in immune response within the testicular environment. However, their involvement in steroid hormone synthesis, particularly testosterone, has not been fully elucidated. This study aims to explore the capability of TM to synthesize and secrete testosterone de novo and to investigate the regulatory mechanisms involved. RESULTS: Transcriptomic analysis revealed significant expression of Cyp11a1, Cyp17a1, Hsd3b1, and Hsd17b3 in TM, which are key enzymes in the testosterone synthesis pathway. qPCR analysis and immunofluorescence validation confirmed the autonomous capability of TM to synthesize testosterone. Ablation of TM in mice resulted in decreased physiological testosterone levels, underscoring the significance of TM in maintaining testicular testosterone levels. Additionally, the study also demonstrated that Cebpb regulates the expression of these crucial genes, thereby modulating testosterone synthesis. CONCLUSIONS: This research establishes that TM possess the autonomous capacity to synthesize and secrete testosterone, contributing significantly to testicular testosterone levels. The transcription factor Cebpb plays a crucial role in this process by regulating the expression of key genes involved in testosterone synthesis.

Mechanism Exploration of the Photoelectrochemical Immunoassay for the Integration of Radical Generation with Self-Quenching.

Photoelectrochemical (PEC) sensing mechanisms based on enzyme-catalyzed strategies primarily achieve the quantitative analysis of biomolecules through the enhancement or attenuation of photocurrent signals. However, there are still no reports that delve into the principles of photocurrent signaling conversion in the reaction between photoactive materials and the biomolecules. In this work, we demonstrated that indium oxysulfide InOS-0.5 heterojunction has excellent peroxidase activity to catalyze the reaction of H2O2-generated hydroxyl radicals (•OH) with the self-generated electrons, thereby resulting in synergistic quenching of the photocurrent signal. Based on the above principles, we coupled InOS-0.5 with a sandwich-type immunoassay to introduce H2O2 production catalyzed by glucose oxidase for the development of a PEC immunosensing platform. H2O2 reacted with InOS-0.5 to produce •OH with strong oxidizing properties, thus quenching the photogenerated electrons and realizing the PEC detection of the carcinoembryonic antigen (CEA, as a model analyte). The photocurrent intensity decreases with the logarithmic increase in CEA concentration (0.02-50 ng mL-1), with a remarkable limit of detection of 8.9 pg mL-1 (S/N = 3). This study further investigates the mechanism of hydrogen peroxide-induced photocurrent quenching, providing deeper insights into the mechanisms of electron-hole transport in hollow porous semiconductor materials and paving the way for the development of efficient PEC sensors.

Discovery of a Highly Promising Disulfide Derivative Scaffold as Inhibitor of SARS-CoV-2 main protease.

The main protease (Mpro) of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) represents a promising target for antiviral drugs aimed at combating COVID-19. Consequently, the development of Mpro inhibitor  is an ideal strategy for combating the virus. In this study, we identified twenty-two dithiocarbamates (1a-h), dithiocarbamate-Cu(II) complexes (2a-hCu) and disulfide derivatives (2a-e, 2i) as potent inhibitors of Mpro, with IC50 value range of 0.09-0.72, 0.9-24.7 and 15.1-111 µM, respectively, through FRET screening. The enzyme kinetics, inhibition mode, jump dilution, and DTT assay revealed that 1g may be a partial reversible inhibitor, while 2d and 2f-Cu are the irreversible and dose- and time-dependent inhibitors, potentially covalently binding to the target. Binding of 2d, 2f-Cu and 1g to Mpro was found to decrease the stability of the protein. Additionally, DTT assays and thermal shift assays indicated that 2f-Cu and 2d are the nonspecific and promiscuous cysteine protease inhibitor. ICP-MS implied that the inhibitory activity of 2f-Cu may stem from the uptake of Cu(II) by the enzyme. Cytotoxicity assays demonstrated that 2d and 1g exhibit low cytotoxicity, whereas 2f-Cu show certain cytotoxicity in L929 cells. Overall, this work presents two promising scaffolds for the development of Mpro inhibitors to combat COVID-19.

Optimizing Surgical Choices of Renal Artery Aneurysm With Sequential Use of "Two-Click AVA" Technique and FlightPlan for Embolization: A Report of Two Cases.

BACKGROUND: Selecting intervention strategies for renal artery aneurysms (RAAs) is challenging especially for those located at the vessel bifurcation. The relationship between the aneurysm and renal branches could not always be accurately viewed from traditional computed tomography angiography (CTA) images. CASE PRESENTATION: This study proposed a new method to investigate the anatomy and affected vessel branches of RAAs using automated software. Two patients with RAAs located at the renal artery bifurcation underwent Cone beam CTA (CBCTA) analysis. We sequentially coupled the "two-click AVA" function of Vessel IQ Xpress (GE Healthcare) with the "vascular tree extraction" function from FlightPlan for Embolization (GE Healthcare) to evaluate the relationship among the main renal artery, vessel branches, and aneurysms. The results showed that one patient had 1 out of 3 branches affected by the aneurysm, whereas the other's branches were all affected. Endovascular repair and open surgery were performed respectively based on the image analysis. Both patients recovered well at follow-up examination. CONCLUSIONS: Based on CBCTA analysis, the combination use of the "two-click AVA" function of VesselIQ Xpress and FlightPlan for Embolization software could assist in aneurysm assessment and intervention choices for RAAs.

The clinical significance and anti-tumor role of PRKG1 in bladder cancer.

Introduction: cGMP-dependent protein kinase 1 (PRKG1) has shown to be associated with some tumorigenesis, while the role of PRKG1 in bladder cancer is unclear. Methods: To investigate the biological and clinical significance of PRKG1 in bladder cancer, we detected the expression of PRKG1 and explored the function of PRKG1 in bladder cancer cells. The PRKG1 transcripts data was downloaded from The Cancer Genome Atlas (TCGA) database, and immunohistochemistry staining was conducted on formalin-fixed paraffin-embedded (FFPE) sample tissues. Relationship between clinical characteristics of patients and expression of PRKG1 was analyzed in FFPE samples, TCGA database, and GSE19423 dataset. PRKG1 was over-expressed, and cell proliferation, migration, invasion, apoptosis, and spheroidizing ability were then detected. Chemosensitivity to cisplatin was detected with cell viability, and half-maximal drug inhibitory concentration (IC50) was calculated. In addition, the relation between PRKG1 expression and the infiltration level of tumor immune cells in tumor microenvironment were analyzed. Results: The results showed expression of PRKG1 was lower in bladder cancer, compared with normal tissues both at protein and transcript levels. Lower PRKG1 expression was related to higher tumor grade, T stage, and muscle invasion, also predicted worse overall survival and recurrence free survival in patients treated with Bacillus Calmette-Guerin (BCG) intravesical immunotherapy. Analysis of tumor immune cells infiltration showed lower PRKG1 was associated with non-inflamed tumor microenvironment. Conclusion: The present study firstly identified the anti-tumor role and tumor immune regulatory role of PRKG1, also found loss of PRKG1 could be used as a prognosis factor. The present study provided a potential biomarker and therapy target to bladder cancer.

PM2.5 Exposure Inhibits Transepithelial Anion Short-circuit Current by Downregulating P2Y2 Receptor/CFTR Pathway.

Fine particulate matter (PM2.5) can damage airway epithelial barriers. The anion transport system plays a crucial role in airway epithelial barriers. However, the detrimental effect and mechanism of PM2.5 on the anion transport system are still unclear. In this study, airway epithelial cells and ovalbumin (OVA)-induced asthmatic mice were used. In transwell model, the adenosine triphosphate (ATP)-induced transepithelial anion short-circuit current (Isc) and airway surface liquid (ASL) significantly decreased after PM2.5 exposure. In addition, PM2.5 exposure decreased the expression levels of P2Y2R, CFTR and cytoplasmic free-calcium, but ATP can increase the expressions of these proteins. PM2.5 exposure increased the levels of Th2-related cytokines of bronchoalveolar lavage fluid, lung inflammation, collagen deposition and hyperplasisa of goblet cells. Interestingly, the administration of ATP showed an inhibitory effect on lung inflammation induced by PM2.5. Together, our study reveals that PM2.5 impairs the ATP-induced transepithelial anion Isc through downregulating P2Y2R/CFTR pathway, and this process may participate in aggravating airway hyperresponsiveness and airway inflammation. These findings may provide important insights on PM2.5-mediated airway epithelial injury.

Circular RNA-based neoantigen vaccine for hepatocellular carcinoma immunotherapy.

mRNA vaccines are regarded as a highly promising avenue for next-generation cancer therapy. Nevertheless, the intricacy of production, inherent instability, and low expression persistence of linear mRNA significantly restrict their extensive utilization. Circular RNAs (circRNAs) offer a novel solution to these limitations due to their efficient protein expression ability, which can be rapidly generated in vitro without the need for extra modifications. Here, we present a novel neoantigen vaccine based on circRNA that induces a potent anti-tumor immune response by expressing hepatocellular carcinoma-specific tumor neoantigens. By cyclizing linearRNA molecules, we were able to enhance the stability of RNA vaccines and form highly stable circRNA molecules with the capacity for sustained protein expression. We confirmed that neoantigen-encoded circRNA can promote dendritic cell (DC) activation and enhance DC-induced T-cell activation in vitro, thereby enhancing T-cell killing of tumor cells. Encapsulating neoantigen-encoded circRNA within lipid nanoparticles for in vivo expression has enabled the creation of a novel circRNA vaccine platform. This platform demonstrates superior tumor treatment and prevention in various murine tumor models, eliciting a robust T-cell immune response. Our circRNA neoantigen vaccine offers new options and application prospects for neoantigen immunotherapy in solid tumors.

Predictive Value of Serum Soluble ST2 in Adult Patients Undergoing Cardiac Surgery for Acute Kidney Injury.

INTRODUCTION: Cardiac surgery is related to an increased risk of postoperative acute kidney injury (AKI). Serum soluble ST2 (sST2) is highly predictive of several cardiovascular diseases and may also be involved in renal injury. This study explored the relationship between serum sST2 levels measured at intensive care unit (ICU) admission and the development of AKI after cardiac surgery. METHODS: We prospectively conducted an investigation on consecutive patients who underwent cardiac surgery. sST2 was immediately measured at ICU admission. The relationship between the levels of sST2 and the development of AKI was explored using stepwise logistic regression. RESULTS: Among the 500 patients enrolled, AKI was observed in 207 (41%) patients. Serum sST2 levels in AKI patients were higher than those without AKI (61.46 ng/mL [46.52, 116.25] vs. 38.91 ng/mL [28.74, 50.93], p < 0.001). Additionally, multivariable logistic regression analysis showed that as progressively higher tertiles of serum sST2, the odds ratios (ORs) of AKI gradually increased (adjusted ORs of 1.97 [95% CI, 1.13-3.45], and 4.27 [95% CI, 2.36-7.71] for tertiles 2 and 3, respectively, relative to tertile 1, p < 0.05). The addition of sST2 further improved reclassification (p < 0.001) and discrimination (p < 0.001) over the basic model, which included established risk factors. CONCLUSION: Serum sST2 levels at ICU admission were associated with the development of postoperative AKI and improved the identification of AKI after cardiac surgery.

Multifunctional Biomimetic Nanocarriers for Dual-Targeted Immuno-Gene Therapy Against Hepatocellular Carcinoma.

Growing evidences have proved that tumors evade recognition and attack by the immune system through immune escape mechanisms, and PDL1/Pbrm1 genes have a strong correlation with poor response or resistance to immune checkpoint blockade (ICB) therapy. Herein, a multifunctional biomimetic nanocarrier (siRNA-CaP@PD1-NVs) is developed, which can not only enhance the cytotoxic activity of immune cells by blocking PD1/PDL1 axis, but also reduce tumor immune escape via Pbrm1/PDL1 gene silencing, leading to a significant improvement in tumor immunosuppressive microenvironment. Consequently, the nanocarrier promotes DC cell maturation, enhances the infiltration and activity of CD8+ T cells, and forms long-term immune memory, which can effectively inhibit tumor growth or even eliminate tumors, and prevent tumor recurrence and metastasis. Overall, this study presents a powerful strategy for co-delivery of siRNA drugs, immune adjuvant, and immune checkpoint inhibitors, and holds great promise for improving the effectiveness and safety of current immunotherapy regimens.

Early warning of hepatocellular carcinoma in cirrhotic patients by three-phase CT-based deep learning radiomics model: a retrospective, multicentre, cohort study.

Background: The diagnosis of hepatocellular carcinoma (HCC) often experiences latency, ultimately leading to unfavorable patient outcomes due to delayed therapeutic interventions. Our study is designed to develop and validate a model that employs triple-phase computerized tomography (CT)-based deep learning radiomics and clinical variables for early warning of HCC in patients with cirrhosis. Methods: We studied 1858 patients with cirrhosis primarily from the PreCar cohort (NCT03588442) between June 2018 and January 2020 at 11 centres, and collected triple-phase CT images and laboratory results 3-12 months prior to HCC diagnosis or non-HCC final follow-up. Using radiomics and deep learning techniques, early warning model was developed in the discovery cohort (n = 924), and then validated in an internal validation cohort (n = 231), and an external validation cohort from 10 external centres (n = 703). Findings: We developed a hybrid model, named ALARM model, which integrates deep learning radiomics with clinical variables, enabling early warning of the majority of HCC cases. The ALARM model effectively predicted short-term HCC development in cirrhotic patients with area under the curve (AUC) of 0.929 (95% confidence interval 0.918-0.941) in the discovery cohort, 0.902 (0.818-0.987) in the internal validation cohort, and 0.918 (0.898-0.961) in the external validation cohort. By applying optimal thresholds of 0.21 and 0.65, the high-risk (n = 221, 11.9%) and medium-risk (n = 433, 23.3%) groups, which covered 94.4% (84/89) of the patients who developed HCC, had significantly higher rates of HCC occurrence compared to the low-risk group (n = 1204, 64.8%) (24.3% vs 6.4% vs 0.42%, P < 0.001). Furthermore, ALARM also demonstrated consistent performance in subgroup analysis. Interpretation: The novel ALARM model, based on deep learning radiomics with clinical variables, provides reliable estimates of short-term HCC development for cirrhotic patients, and may have the potential to improve the precision in clinical decision-making and early initiation of HCC treatments. Funding: This work was supported by National Key Research and Development Program of China (2022YFC2303600, 2022YFC2304800), and the National Natural Science Foundation of China (82170610), Guangdong Basic and Applied Basic Research Foundation (2023A1515011211).

Machine learning-based model to predict severe acute kidney injury after total aortic arch replacement for acute type A aortic dissection.

Background: Severe acute kidney injury (AKI) after total aortic arch replacement (TAAR) is related to adverse outcomes in patients with acute type A aortic dissection (ATAAD). However, the early prediction of severe AKI remains a challenge. This study aimed to develop a novel model to predict severe AKI after TAAR in ATAAD patients using machine learning algorithms. Methods: A total of 572 ATAAD patients undergoing TAAR were enrolled in this retrospective study, and randomly divided into a training set (70 %) and a validation set (30 %). Lasso regression, support vector machine-recursive feature elimination and random forest algorithms were used to screen indicators for severe AKI (defined as AKI stage III) in the training set, respectively. Then the intersection indicators were selected to construct models through artificial neural network (ANN) and logistic regression. The AUC-ROC curve was employed to ascertain the prediction efficacy of the ANN and logistic regression models. Results: The incidence of severe AKI after TAAR was 22.9 % among ATAAD patients. The intersection predictors identified by different machine learning algorithms were baseline serum creatinine and ICU admission variables, including serum cystatin C, procalcitonin, aspartate transaminase, platelet, lactic dehydrogenase, urine N-acetyl-ß-d-glucosidase and Acute Physiology and Chronic Health Evaluation II score. The ANN model showed a higher AUC-ROC than logistic regression (0.938 vs 0.908, p < 0.05). Furthermore, the ANN model could predict 89.1 % of severe AKI cases beforehand. In the validation set, the superior performance of the ANN model was further confirmed in terms of discrimination ability (AUC = 0.916), calibration curve analysis and decision curve analysis. Conclusion: This study developed a novel and reliable clinical prediction model for severe AKI after TAAR in ATAAD patients using machine learning algorithms. Importantly, the ANN model showed a higher predictive ability for severe AKI than logistic regression.

Multi-Enzyme Cascade Nanoreactors for High-Throughput Immunoassay: Transitioning Concept in Lab to Application in Community.

In this work, we reported a cholesterol oxidase (Chox)-loaded platinum (Pt) nanozyme with the collaborative cascade nanoreactor for the construction of nanozyme-enzyme-linked immunosorbent assay (N-ELSA) models to realize high-throughput rapid evaluation of cancer markers. Considering the high specific surface area and manipulable surface sites, ZIF-8 was used as a substrate for natural enzyme and nanozyme loading. The constructed ZIF-8-Pt nanozyme platform exhibited efficient enzyme-like catalytic efficiency with a standard corrected activity of 60.59 U mg-1, which was 12 times higher than that of the ZIF-8 precursor, and highly efficient photothermal conversion efficiency (∼35.49%). In N-ELISA testing, developed multienzyme photothermal probes were immobilized in microplates based on antigen-antibody-specific reactions. Cholesterol was reacted in a cascade to reactive oxygen radicals, which attacked 3,3',5,5'-tetramethylbenzidine, causing it to oxidize and color change, thus exhibiting highly enhanced efficient photothermal properties. Systematic temperature evaluations were performed by a hand-held microelectromechanical system thermal imager under the excitation of an 808 nm surface light source to determine the cancer antigen 15-3 (CA15-3) profiles in the samples. Encouragingly, the temperature signal from the microwells increased with increasing CA15-3, with a linear range of 2 mU mL-1 to 100 U mL-1, considering it to be the sensor with the widest working range for visualization and portability available. This work provides new horizons for the development of efficient multienzyme portable colorimetric-photothermal platforms to help advance the community-based process of early cancer detection.

Tumour-microenvironment-responsive Na2S2O8 nanocrystals encapsulated in hollow organosilica-metal-phenolic networks for cycling persistent tumour-dynamic therapy.

Traditional tumour-dynamic therapy still inevitably faces the critical challenge of limited reactive oxygen species (ROS)-generating efficiency due to tumour hypoxia, extreme pH condition for Fenton reaction, and unsustainable mono-catalytic reaction. To fight against these issues, we skilfully develop a tumour-microenvironment-driven yolk-shell nanoreactor to realize the high-efficiency persistent dynamic therapy via cascade-responsive dual cycling amplification of •SO4 -/•OH radicals. The nanoreactor with an ultrahigh payload of free radical initiator is designed by encapsulating the Na2S2O8 nanocrystals into hollow tetra-sulphide-introduced mesoporous silica (HTSMS) and afterward enclosed by epigallocatechin gallate (EG)-Fe(II) cross-linking. Within the tumour microenvironment, the intracellular glutathione (GSH) can trigger the tetra-sulphide cleavage of nanoreactors to explosively release Na+/S2O8 2 - /Fe2+ and EG. Then a sequence of cascade reactions will be activated to efficiently generate •SO4 - (Fe2+-catalyzed S2O8 2 - oxidation), proton (•SO4 --catalyzed H2O decomposition), and •OH (proton-intensified Fenton oxidation). Synchronously, the oxidation-generated Fe3+ will be in turn recovered into Fe2+ by excessive EG to circularly amplify •SO4 -/•OH radicals. The nanoreactors can also disrupt the intracellular osmolarity homeostasis by Na+ overload and weaken the ROS-scavenging systems by GSH exhaustion to further amplify oxidative stress. Our yolk-shell nanoreactors can efficiently eradicate tumours via multiple oxidative stress amplification, which will provide a perspective to explore dynamic therapy.

From structural design to delivery: mRNA therapeutics for cancer immunotherapy.

mRNA therapeutics have emerged as powerful tools for cancer immunotherapy in accordance with their superiority in expressing all sequence-known proteins in vivo. In particular, with a small dosage of delivered mRNA, antigen-presenting cells (APCs) can synthesize mutant neo-antigens and multi-antigens and present epitopes to T lymphocytes to elicit antitumor effects. In addition, expressing receptors like chimeric antigen receptor (CAR), T-cell receptor (TCR), CD134, and immune-modulating factors including cytokines, interferons, and antibodies in specific cells can enhance immunological response against tumors. With the maturation of in vitro transcription (IVT) technology, large-scale and pure mRNA encoding specific proteins can be synthesized quickly. However, the clinical translation of mRNA-based anticancer strategies is restricted by delivering mRNA into target organs or cells and the inadequate endosomal escape efficiency of mRNA. Recently, there have been some advances in mRNA-based cancer immunotherapy, which can be roughly classified as modifications of the mRNA structure and the development of delivery systems, especially the lipid nanoparticle platforms. In this review, the latest strategies for overcoming the limitations of mRNA-based cancer immunotherapies and the recent advances in delivering mRNA into specific organs and cells are summarized. Challenges and opportunities for clinical applications of mRNA-based cancer immunotherapy are also discussed.

Inhibition of FSP1: A new strategy for the treatment of tumors (Review).

Ferroptosis, a regulated form of cell death, is intricately linked to iron­dependent lipid peroxidation. Recent evidence strongly supports the induction of ferroptosis as a promising strategy for treating cancers resistant to conventional therapies. A key player in ferroptosis regulation is ferroptosis suppressor protein 1 (FSP1), which promotes cancer cell resistance by promoting the production of the antioxidant form of coenzyme Q10. Of note, FSP1 confers resistance to ferroptosis independently of the glutathione (GSH) and glutathione peroxidase­4 pathway. Therefore, targeting FSP1 to weaken its inhibition of ferroptosis may be a viable strategy for treating refractory cancer. This review aims to clarify the molecular mechanisms underlying ferroptosis, the specific pathway by which FSP1 suppresses ferroptosis and the effect of FSP1 inhibitors on cancer cells.

Light and gas dual-function detection and mutual enhancement based on hyperdoped black silicon.

We introduce a unique dual-function detector with an asymmetric light illumination based on the black silicon co-hyperdoped with sulfur and nitrogen for light and gas detection, and the properties in NO2 gas sensing and photoelectric detection are studied under various light and gas environments, respectively. Enhanced performance of the device under certain light and gas conditions is observed. When illuminated at the optimal wavelength, the gas sensors' responsivity to NO2 can be enhanced by approximately 5 to 200 times over 730 nm illumination, respectively. The photodetectors' photoresponsivity increases 15 to 200 times in a 300 ppm NO2 gas environment compared to air. Such mutual enhancement achieved through the clever combination of light and gas implies a novel approach to improve the performance of the black silicon detectors in both gas sensing and photoelectric detection.

Guanine-Rich RNA Sequence Binding Factor 1 Deficiency Promotes Colorectal Cancer Progression by Regulating PI3K/AKT Signaling Pathway.

Background: Guanine-rich RNA sequence binding factor 1 (GRSF1), part of the RNA-binding protein family, is now attracting interest due to its potential association with the progression of a variety of human cancers. The precise contribution and molecular mechanism of GRSF1 to colorectal cancer (CRC) progression, however, have yet to be clarified. Methods: Immunohistochemistry and Western Blot analysis was carried out to detect the expression of GRSF1 in CRC at both mRNA and protein levels and its subsequent effects on prognosis. A series of functional tests were performed to understand its influence on proliferation, migration, and invasion of CRC cells. Results: The universal downregulation of GRSF1 in CRC was identified, indicating a correlation with poor prognosis. Our functional studies unveiled that the elimination of GRSF1 enhances tumour activities such as proliferation, migration, and invasion of CRC cells, while GRSF1 overexpression curtailed these abilities. Conclusion: Notably, we uncovered that GRSF1 insufficiency modulates the PI3K/Akt signaling pathway and Ras activation in CRC. Therefore, our data suggest GRSF1 operates as a tumor suppressor gene in CRC and may offer promise as a potential biomarker and novel therapeutic target in CRC management.

Pt/Zn-TCPP Nanozyme-Based Flexible Immunoassay for Dual-Mode Pressure-Temperature Monitoring of Low-Abundance Proteins.

Pressure and temperature, as common physical parameters, are important for monitoring human health. In contrast, single-mode monitoring is prone to causing experimental errors. Herein, we innovatively designed a dual-mode flexible sensing platform based on a platinum/zinc-meso-tetrakis(4-carboxyphenyl)porphyrin (Pt/Zn-TCPP) nanozyme for the quantitative monitoring of carcinoembryonic antigen (CEA) in biological fluids with pressure and temperature readouts. The Pt/Zn-TCPP nanozyme with catalytic and photothermal efficiencies was synthesized by means of integrating photosensitizers into porous materials. The flexible sensing system after the antigen-antibody reaction recognized the pressure using a flexible skin-like pressure sensor with a digital multimeter readout, whereas the temperature was acquired via the photoheat conversion system of the Pt/Zn-TCPP nanozyme under 808 nm near-infrared (NIR) irradiation using a portable NIR imaging camera on a smartphone. Meanwhile, the dual-mode flexible sensing system was carried out on a homemade three-dimensional (3D)-printed device. Results revealed that the developed dual-mode immunosensing platform could exhibit good pressure and temperature responses within the dynamic range of 0.5-100 ng mL-1 CEA with the detection limits of 0.24 and 0.13 ng mL-1, respectively. In addition, the pressure and temperature were sensed simultaneously without crosstalk interference. Importantly, the dual-mode flexible immunosensing system can effectively avoid false alarms during the measurement, thus providing great potential for simple and low-cost development for point-of-care testing.