A new perspective on prostate cancer treatment: the interplay between cellular senescence and treatment resistance.

The emergence of resistance to prostate cancer (PCa) treatment, particularly to androgen deprivation therapy (ADT), has posed a significant challenge in the field of PCa management. Among the therapeutic options for PCa, radiotherapy, chemotherapy, and hormone therapy are commonly used modalities. However, these therapeutic approaches, while inducing apoptosis in tumor cells, may also trigger stress-induced premature senescence (SIPS). Cellular senescence, an entropy-driven transition from an ordered to a disordered state, ultimately leading to cell growth arrest, exhibits a dual role in PCa treatment. On one hand, senescent tumor cells may withdraw from the cell cycle, thereby reducing tumor growth rate and exerting a positive effect on treatment. On the other hand, senescent tumor cells may secrete a plethora of cytokines, growth factors and proteases that can affect neighboring tumor cells, thereby exerting a negative impact on treatment. This review explores how radiotherapy, chemotherapy, and hormone therapy trigger SIPS and the nuanced impact of senescent tumor cells on PCa treatment. Additionally, we aim to identify novel therapeutic strategies to overcome resistance in PCa treatment, thereby enhancing patient outcomes.

Alkyne-tagged SERS nanoprobe for understanding Cu+ and Cu2+ conversion in cuproptosis processes.

Simultaneously quantifying mitochondrial Cu+ and Cu2+ levels is crucial for evaluating the molecular mechanisms of copper accumulation-involved pathological processes. Here, a series of molecules containing various diacetylene derivatives as Raman reporters are designed and synthesized, and the alkyne-tagged SERS probe is created for determination Cu+ and Cu2+ with high selectivity and sensitivity. The developed SERS probe generates well-separated distinguishable Raman fingerprint peaks with built-in corrections in the cellular silent region, resulting in accurate quantification of Cu+ and Cu2+. The present probe demonstrates high tempo-spatial resolution for real-time imaging and simultaneously quantifying mitochondrial Cu+ and Cu2+ with long-term stability benefiting from the probe assembly with designed Au-C≡C groups. Using this powerful tool, it is found that mitochondrial Cu+ and Cu2+ increase during ischemia are associated with breakdown of proteins containing copper as well as conversion of Cu+ and Cu2+. Meanwhile, we observe that parts of Cu+ and Cu2+ are transported out of neurons by ATPase. More importantly, cuproptosis in neurons is found including the oxidative stress process caused by the conversion of Cu+ to Cu2+, which dominates at the early stage (<9 h), and subsequent proteotoxic stress. Both oxidative and proteotoxic stresses contribute to neuronal death.

Enhanced cellular therapy: revolutionizing adoptive cellular therapy.

Enhanced cellular therapy has emerged as a novel concept following the basis of cellular therapy. This treatment modality applied drugs or biotechnology to directly enhance or genetically modify cells to enhance the efficacy of adoptive cellular therapy (ACT). Drugs or biotechnology that enhance the killing ability of immune cells include immune checkpoint inhibitors (ICIs) / antibody drugs, small molecule inhibitors, immunomodulatory factors, proteolysis targeting chimera (PROTAC), oncolytic virus (OV), etc. Firstly, overcoming the inhibitory tumor microenvironment (TME) can enhance the efficacy of ACT, which can be achieved by blocking the immune checkpoint. Secondly, cytokines or cytokine receptors can be expressed by genetic engineering or added directly to adoptive cells to enhance the migration and infiltration of adoptive cells to tumor cells. Moreover, multi-antigen chimeric antigen receptors (CARs) can be designed to enhance the specific recognition of tumor cell-related antigens, and OVs can also stimulate antigen release. In addition to inserting suicide genes into adoptive cells, PROTAC technology can be used as a safety switch or degradation agent of immunosuppressive factors to enhance the safety and efficacy of adoptive cells. This article comprehensively summarizes the mechanism, current situation, and clinical application of enhanced cellular therapy, describing potential improvements to adoptive cellular therapy.

Knowledge mapping of application of image-guided surgery in prostate cancer: a bibliometric analysis (2013-2023).

BACKGROUND: Image-guided surgery (IGS) refers to surgery navigated by medical imaging technology, helping doctors better clarify tumor boundaries, identify metastatic lymph nodes and preserve surrounding healthy tissue function. Recent studies have provided expectable momentum of the application of IGS in prostate cancer (PCa). The authors aim to comprehensively construct a bibliometric analysis of the application of IGS in PCa. METHOD: The authors searched publications related to application of IGS in PCa from 2013 to 2023 on the web of science core collection (WoSCC) databases. VOSviewer, CiteSpace, and R package 'bibliometrix' were used for bibliometric analysis. RESULTS: Two thousand three eighty-nine articles from 75 countries and 2883 institutions led by the United States were included. The number of publications related to the application of IGS in PCa kept high in the last decade. Johns Hopkins University is the top research institutions. Journal of Nuclear Medicine has the highest popularity as the selection of journal and co-cited journal. Pomper Martin G. had published the most paper. Ali Afshar-Oromieh was co-cited most frequently. The clinical efficacy of PSMA-PET/CT in PCa diagnosis and treatment are main topics in this research field, with emerging focuses on the use of fluorescence imaging guidance technology in PCa. 'PSMA' and 'PET/CT' are the main keywords as long-term research hotspots. CONCLUSION: This study is the first bibliometric analysis of researches on application of IGS in PCa with three recognized bibliometric software, providing an objective description and comprehensive guidance for the future relevant investigations.

Molecular insights into sarcopenia: ferroptosis-related genes as diagnostic and therapeutic targets.

Ferroptosis, characterized by iron accumulation and lipid peroxidation, leads to cell death. Growing evidence suggests the involvement of ferroptosis in sarcopenia. However, the fundamental ferroptosis-related genes (FRGs) for sarcopenia diagnosis, prognosis, and therapy remain elusive. This study aimed to identify molecular biomarkers of ferroptosis in sarcopenia patients. Gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between normal and sarcopenia samples were identified using the 'limma' package in R software. FRGs were extracted from GeneCards and FerrDB databases. Functional enrichment analysis determined the roles of DEGs using the 'clusterProfiler' package. A protein-protein network was constructed using Cytoscape software. Immune infiltration analysis and receiver operating characteristic (ROC) analysis were performed. mRNA-miRNA, mRNA-TF, and mRNA-drug interactions were predicted using ENCORI, hTFtarget, and CHIPBase databases. The network was visualized using Cytoscape. We identified 46 FRGs in sarcopenia. Functional enrichment analysis revealed their involvement in critical biological processes, including responses to steroid hormones and glucocorticoids. KEGG enrichment analysis implicated pathways such as carbon metabolism, ferroptosis, and glyoxylate in sarcopenia. Totally, 11 hub genes were identified, and ROC analysis demonstrated their potential as sensitive and specific markers for sarcopenia in both datasets. Additionally, differences in immune cell infiltration were observed between normal and sarcopenia samples. The hub genes identified in this study are closely associated with ferroptosis in sarcopenia and can effectively differentiate sarcopenia from controls. CDKN1A, CS, DLD, FOXO1, HSPB1, LDHA, MDH2, and YWHAZ show high sensitivity and specificity for sarcopenia diagnosis.Communicated by Ramaswamy H. Sarma.

Chitosan nanofiber paper used as separator for high performance and sustainable lithium-ion batteries.

Separators are indispensable components in lithium-ion batteries (LIBs), providing efficient pathways for lithium ions to travel and isolating the positive and negative electrodes to avoid short circuits. However, traditional polyolefin-based separators exhibit inferior electrolyte affinities, limited porosities, and low thermal stabilities. In this study, a novel method was developed to prepare chitosan micro/nanofiber membranes as LIB separators using natural materials. The pore sizes of the chitosan micro/nanofibers separators were modulated by changing the diameters of the chitosan fibers. The results demonstrated that the chitosan nanofiber separators (CSNFs) had superior electrolyte uptake (281 %), excellent thermal dimensional stability, and electrochemical performance in LiFePO4/Li half-cell, as indicated by the higher discharge capacity after 100 cycles, and higher rate capacity than commercial Celgard2325 separator. This study paves the way for the fabrication of eco-efficient and environment-friendly separators for high-performance LIBs.

Chitosan nanofibrous scaffold with graded and controlled release of ciprofloxacin and BMP-2 nanoparticles for the conception of bone regeneration.

The repair of bone defects using grafts is commonly employed in clinical practice. However, the risk of infection poses a significant concern. Tissue engineering scaffolds with antibacterial functionalities offer a better approach for bone tissue repair. In this work, firstly, two kinds of nanoparticles were prepared using chitosan to complex with ciprofloxacin and BMP-2, respectively. The ciprofloxacin complex nanoparticles improved the dissolution efficiency of ciprofloxacin achieving a potent antibacterial effect and cumulative release reached 95 % in 7 h. For BMP-2 complexed nanoparticles, the release time points can be programmed at 80 h, 100 h or 180 h by regulating the number of coating chitosan layers. Secondly, a functional scaffold was prepared by combining the two nanoparticles with chitosan nanofibers. The microscopic nanofiber structure of the scaffold with 27.28 m2/g specific surface area promotes cell adhesion, high porosity provides space for cell growth, and facilitates drug loading and release. The multifunctional scaffold exhibits programmed release function, and has obvious antibacterial effect at the initial stage of implantation, and releases BMP-2 to promote osteogenic differentiation of mesenchymal stem cells after the antibacterial effect ends. The scaffold is expected to be applied in clinical bone repair and graft infection prevention.

Diabetes and incidence of breast cancer and its molecular subtypes: A systematic review and meta-analysis.

Diabetes mellitus (DM) has been proposed to be positively associated with breast cancer (BCa) risk due to shared risk factors, metabolic dysfunction, and the use of antidiabetic medications. We conducted a systematic review and meta-analysis to evaluate the association between DM and BCa risk. We searched PubMed, Embase, and Web of Science for cohort and case-control studies assessing the association between DM and BCa published before 10 December 2021. Two reviewers independently screened the studies for inclusion, abstracted article data, and rated study quality. Random effects models were used to estimate summary risk ratios (RRs) and 95% confidence intervals (CIs). From 8396 articles identified in the initial search, 70 independent studies were included in the meta-analysis. DM was associated with an overall increased risk of BCa (RR = 1.20, 95% CI: 1.11-1.29). The 24 case-control studies demonstrated a stronger association (RR = 1.26, 95% CI: 1.13-1.40) than the 46 cohort studies (RR = 1.15, 95% CI: 1.05-1.27). Studies reporting risk by menopausal status found that postmenopausal women had an elevated risk of developing BCa (RR = 1.12, 95% CI: 1.07-1.17). No association between DM and BCa risk was observed among premenopausal women (RR = 0.95, 95% CI: 0.85-1.05). In addition, DM was associated with significantly increased risks of oestrogen receptor (ER)+ (RR = 1.09, 95% CI: 1.00-1.20), ER- (RR = 1.16, 95% CI: 1.04-1.30), and triple negative BCa (RR = 1.41, 95% CI: 1.01-1.96). The association estimate for human epidermal growth factor 2-positive BCa was also positive (RR = 1.21, 95% CI: 0.52-2.82), but the CI was wide and crossed the null. Our meta-analysis confirms a modest positive association between DM and BCa risk. In addition, our results suggest that the association between DM and BCa may be modified by menopausal status, and that DM may be differentially associated with BCa subtypes defined by receptor status. Additional studies are warranted to investigate the mechanisms underlying these associations and any influence of DM on BCa receptor expression.

Enhancing the Piezoelectric Properties of 3D Printed PVDF Using Concurrent Torsional Shear Strain.

Extrusion-based polymer 3D printing induces shear strains within the material, influencing its rheological and mechanical properties. In materials like polyvinylidene difluoride (PVDF), these strains stretch polymer chains, leading to increased crystallinity and improved piezoelectric properties. This study demonstrates a 400% enhancement in the piezoelectric property of extrusion-printed PVDF by introducing additional shear strains during the printing process. The continuous torsional shear strains, imposed via a rotating extrusion nozzle, results in additional crystalline ß-phases, directly impacting the piezoelectric behavior of the printed parts. The effect of the nozzle's rotational speed on the amount of ß-phase formation is characterized using FTIR. This research introduces a new direction in the development of polymer and composite 3D printing, where in-process shear strains are used to control the alignment of polymer chains and/or in-fill phases and the overall properties of printed parts.

Novel androgen receptor inhibitors for metastatic hormone-sensitive prostate cancer: Current application and future perspectives.

Androgen receptor (AR) signaling is essential in prostate cancer treatment. For many years, androgen deprivation therapy (ADT) has been primarily applied to manage advanced prostate cancer. However, most individuals with metastatic hormone-sensitive prostate cancer (mHSPC) administered ADT alone are at risk of developing metastatic castration-resistant prostate cancer (mCRPC) in less than two years. New approaches employing novel AR inhibitors (ARi) as intensified upfront systemic treatment in mHSPC have recently demonstrated substantial benefits in delaying disease progression and prolonging overall survival. Administration of novel ARi has become the new standard of care in mHSPC. The new landscape simultaneously makes treatment choice more challenging. This review provides comprehensive data on molecular structure, pharmaceutical properties, and efficacy and safety profiles reported by pivotal clinical trials. We also discuss future directions with ongoing Phase III trials of novel ARi in mHSPC. Considering these biological and clinical insights, this review aimed to provide a comprehensive understanding of differences in the development and applications of novel ARi for mHSPC, which may be helpful in designing strategies for first-line treatment choices.

A Light-Thin Chitosan Nanofiber Separator for High-Performance Lithium-Ion Batteries.

With the development of portable devices and wearable devices, there is a higher demand for high-energy density and light lithium-ion batteries (LIBs). The separator is a significant component directly affecting the performance of LIBs. In this paper, a thin and porous chitosan nanofiber separator was successfully fabricated using the simple ethanol displacement method. The thickness of the CME15 separator was about half that of mainstream commercial Celgard2325 separators. Owing to its inherent polarity and high porosity, the obtained CME15 separator achieved a small contact angle (18°) and excellent electrolyte wettability (324% uptake). The CME15 separator could maintain excellent thermal dimensional stability at 160 °C. Furthermore, the CME15 separator-based LIBs exhibited excellent cycling performance after 100 cycles (117 mAh g-1 at 1 C). The present work offers a perspective on applying a chitosan nanofiber separator in light and high-performance lithium-ion batteries (LIBs).

Interface Healing Between Adjacent Tracks in Fused Filament Fabrication Using In-Process Laser Heating.

Fused filament fabrication is one of the most desired thermal plastic additive manufacturing processes because of its ability to fabricate complex objects with high accessibility. However, due to the extrusion track-based direct write process mechanism, parts built using this method exhibit anisotropic mechanical properties. In this work, an in-process laser heating method is introduced to heal interface adhesion between adjacent deposited tracks by increasing the interface temperature to promote polymer reptation and enhance bonding strength of the interface of adjacent tracks. With the use of laser heating induced interface healing, the measured flexural strength between adjacent tracks in the same layer increased and exceeded that of the control sample tested along the track direction. The effect of laser on interface healing was also verified by investigating the load-displacement curve and morphology analysis of the fractured surface.

A Novel Mobile App for Personalized Dietary Advice Leveraging Persuasive Technology, Computer Vision, and Cloud Computing: Development and Usability Study.

BACKGROUND: The Australian Dietary Guidelines (ADG) translate the best available evidence in nutrition into food choice recommendations. However, adherence to the ADG is poor in Australia. Given that following a healthy diet can be a potentially cost-effective strategy for lowering the risk of chronic diseases, there is an urgent need to develop novel technologies for individuals to improve their adherence to the ADG. OBJECTIVE: This study describes the development process and design of a prototype mobile app for personalized dietary advice based on the ADG for adults in Australia, with the aim of exploring the usability of the prototype. The goal of the prototype was to provide personalized, evidence-based support for self-managing food choices in real time. METHODS: The guidelines of the design science paradigm were applied to guide the design, development, and evaluation of a progressive web app using Amazon Web Services Elastic Compute Cloud services via iterations. The food layer of the Nutrition Care Process, the strategies of cognitive behavioral theory, and the ADG were translated into prototype features guided by the Persuasive Systems Design model. A gain-framed approach was adopted to promote positive behavior changes. A cross-modal image-to-recipe retrieval model under an Apache 2.0 license was deployed for dietary assessment. A survey using the Mobile Application Rating Scale and semistructured in-depth interviews were conducted to explore the usability of the prototype through convenience sampling (N=15). RESULTS: The prominent features of the prototype included the use of image-based dietary assessment, food choice tracking with immediate feedback leveraging gamification principles, personal goal setting for food choices, and the provision of recipe ideas and information on the ADG. The overall prototype quality score was "acceptable," with a median of 3.46 (IQR 2.78-3.81) out of 5 points. The median score of the perceived impact of the prototype on healthy eating based on the ADG was 3.83 (IQR 2.75-4.08) out of 5 points. In-depth interviews identified the use of gamification for tracking food choices and innovation in the image-based dietary assessment as the main drivers of the positive user experience of using the prototype. CONCLUSIONS: A novel evidence-based prototype mobile app was successfully developed by leveraging a cross-disciplinary collaboration. A detailed description of the development process and design of the prototype enhances its transparency and provides detailed insights into its creation. This study provides a valuable example of the development of a novel, evidence-based app for personalized dietary advice on food choices using recent advancements in computer vision. A revised version of this prototype is currently under development.

Pan-cancer analysis reveals the prognostic and immunologic roles of cereblon and its significance for PROTAC design.

Background: Cereblon (CRBN) has emerged as a vital E3 ubiquitin ligase for Proteolysis-targeting chimera (PROTAC) design. However, few studies focus on the physiological mechanism of CRBN, and more studies are needed to explore the influence of CRBN on tumorigenesis. This pan-cancer analysis aims to explore the prognostic and immunologic roles of CRBN, and provide new insight for CRBN into cancer treatment and PROTAC design. Methods: The TCGA database, TIMER 2.0 database, and TISIDB database were used to analyze the role of CRBN in pan-cancer. Multiple bioinformatic methods (ssGSEA, Kaplan-Meier, univariate cox regression, ESTIMATE, CIBERSORT) were applied to investigate the CRBN expression status, gene activity, prognostic values, and its correlation with immune scores, immune infiltration, immune-related functions, HALLMARKs functions, and response to immunotherapy in pan-cancer. Results: In most cancer types, the expression and activity of CRBN in tumor groups were lower compared with normal groups. Upregulated CRBN expression may indicate a better prognosis for cancer patients. The Immune score, stromal score, and tumor purity varied greatly among different cancer types. GSEA analysis showed that high CRBN expression was correlated with the downregulation of tumor-promoting signaling pathways. The level of CRBN was associated with Tumor mutation burden (TMB), Microsatellite instability (MSI), objective response rate (ORR), and immune cell infiltration in a few cancer types. Conclusion: Pan-cancer analysis reveals the potential role of CRBN as a prognostic biomarker and versatile immunologic roles in different cancer types. Upregulated expression of CRBN may be beneficial to CRBN-related immunotherapy and PROTAC design.

The Biological Roles of Puccinia striiformis f. sp. tritici Effectors during Infection of Wheat.

Puccinia striiformis f. sp. tritici (Pst) is the causative agent of wheat stripe rust, which can lead to a significant loss in annual wheat yields. Therefore, there is an urgent need for a deeper comprehension of the basic mechanisms underlying Pst infection. Effectors are known as the agents that plant pathogens deliver into host tissues to promote infection, typically by interfering with plant physiology and biochemistry. Insights into effector activity can significantly aid the development of future strategies to generate disease-resistant crops. However, the functional analysis of Pst effectors is still in its infancy, which hinders our understanding of the molecular mechanisms of the interaction between Pst and wheat. In this review, we summarize the potential roles of validated and proposed Pst effectors during wheat infection, including proteinaceous effectors, non-coding RNAs (sRNA effectors), and secondary metabolites (SMs effectors). Further, we suggest specific countermeasures against Pst pathogenesis and future research directions, which may promote our understanding of Pst effector functions during wheat immunity attempts.

Colloid driven low supersaturation crystallization for atomically thin Bismuth halide perovskite.

It is challenging to grow atomically thin non-van der Waals perovskite due to the strong electronic coupling between adjacent layers. Here, we present a colloid-driven low supersaturation crystallization strategy to grow atomically thin Cs3Bi2Br9. The colloid solution drives low-concentration solute in a supersaturation state, contributing to initial heterogeneous nucleation. Simultaneously, the colloids provide a stable precursor source in the low-concentration solute. The surfactant is absorbed in specific crystal nucleation facet resulting in the anisotropic growth of planar dominance. Ionic perovskite Cs3Bi2Br9 is readily grown from monolayered to six-layered Cs3Bi2Br9 corresponding to thicknesses of 0.7, 1.6, 2.7, 3.6, 4.6 and 5.7 nm. The atomically thin Cs3Bi2Br9 presents layer-dependent nonlinear optical performance and stacking-induced second harmonic generation. This work provides a concept for growing atomically thin halide perovskite with non-van der Waal structures and demonstrates potential application for atomically thin single crystals' growth with strong electronic coupling between adjacent layers.

Interconnections between urolithiasis and oral health: a cross-sectional and bidirectional Mendelian randomization study.

Introduction: Urolithiasis is one of the most common diseases for urologists and it is a heavy burden for stone formers and society. The theory of the oral-genitourinary axis casts novel light on the pathological process of genitourinary system diseases. Hence, we performed this study to characterize the crosstalk between oral health conditions and urolithiasis to provide evidence for prevention measures and mechanisms of stone formation. Materials and methods: This population-based cross-sectional study included 86,548 Chinese individuals who had undergone a comprehensive examination in 2017. Urolithiasis was diagnosed depending on the results of ultrasonographic imaging. Logistic models were utilized to characterize the association between oral health conditions and urolithiasis. We further applied bidirectional Mendelian randomization to explore the causality between oral health conditions and urolithiasis. Results: We observed that presenting caries indicated a negative correlation with the risk for urolithiasis while presenting gingivitis [OR (95% CI), 2.021 (1.866-2.187)] and impacted tooth [OR (95% CI), 1.312 (1.219-1.411)] shown to be positively associated with urolithiasis. Furthermore, we discovered that genetically predicted gingivitis was associated with a higher risk of urolithiasis [OR (95% CI), 1.174 (1.009-1.366)] and causality from urolithiasis to impacted teeth [OR(95% CI), 1.207 (1.027-1.418)] through bidirectional Mendelian randomization. Conclusion: The results cast new light on the risk factor and pathogenesis of kidney stone formation and could provide novel evidence for the oral-genitourinary axis and the systematic inflammatory network. Our findings could also offer suggestions for tailored clinical prevention strategies against stone diseases.

In-Process Orbiting Laser-Assisted Technique for the Surface Finish in Material Extrusion-Based 3D Printing.

Material extrusion-based polymer 3D printing, one of the most commonly used additive manufacturing processes for thermoplastics and composites, has drawn extensive attention due to its capability and cost effectiveness. However, the low surface finish quality of the printed parts remains a drawback due to the nature of stacking successive layers along one direction and the nature of rastering of the extruded tracks of material. In this work, an in-process thermal radiation-assisted, surface reflow method is demonstrated that significantly improves the surface finish of the sidewalls of printed parts. It is observed that the surface finish of the printed part is drastically improved for both flat and curved surfaces. The effect of surface reflow on roughness reduction was characterized using optical profilometry and scanning electron microscopy (SEM), while the local heated spot temperature was quantified using a thermal camera.

Integrated bioinformatic analysis and cell line experiments reveal the significant role of the novel immune checkpoint TIGIT in kidney renal clear cell carcinoma.

Background: T cell immunoglobulin and ITIM domain (TIGIT) is a widely concerned immune checkpoint, which plays an essential role in immunosuppression and immune evasion. However, the role of TIGIT in normal organ tissues and renal clear cell carcinoma is unclear. We aim to identify the critical role of TIGIT in renal clear cell carcinoma and find potential targeted TIGIT drugs. Materials and methods: Data retrieved from the GTEX database and TCGA database was used to investigate the expression of TIGIT in normal whole-body tissues and abnormal pan-cancer, then the transcriptome atlas of patients with kidney renal clear cell carcinoma (KIRC) in the TCGA database were applied to distinguish the TIGIT related features, including differential expression status, prognostic value, immune infiltration, co-expression, and drug response of sunitinib an anti-PD1/CTLA4 immunotherapy in KIRC. Furthermore, we constructed a gene-drug network to discover a potential drug targeting TIGIT and verified it by performing molecular docking. Finally, we conducted real-time polymerase chain reaction (PCR) and assays for Transwell migration and CCK-8 to explore the potential roles of TIGIT. Results: TIGIT showed a moderate expression in normal kidney tissues and was confirmed as an essential prognostic factor that was significantly higher expressed in KIRC tissues, and high expression of TIGIT is associated with poor OS, PFS, and DSS in KIRC. Also, the expression of TIGIT was closely associated with the pathological characteristics of the tumor, high expression of TIGIT in KIRC was observed with several critical functions or pathways such as apoptosis, BCR signaling, TCR signaling et al. Moreover, the expression of TIGIT showed a strong positive correlation with infiltration of CD8+ T cells and Tregs and a positive correlation with the drug sensitivity of sunitinib simultaneously. Further Tide ips score analysis and submap analysis reveal that patients with high TIGIT expression significantly show a better response to anti-PD1 immunotherapy. Following this, we discovered Selumetinib and PD0325901 as potential drugs targeting TIGIT and verified the interaction between these two drugs and TIGIT protein by molecular docking. Finally, we verified the essential role of TIGIT in the proliferation and migration functions by using KIRC cell lines. Conclusions: TIGIT plays an essential role in tumorigenesis and progression in KIRC. High expression of TIGIT results in poor survival of KIRC and high drug sensitivity to sunitinib. Besides, Selumetinib and PD0325901 may be potential drugs targeting TIGIT, and combined therapy of anti-TIGIT and other treatments show great potential in treating KIRC.

High-Density Optophysiology Platform for Recording Intracellular and Extracellular Signals across the Brain of Free-Moving Animals.

Developing a novel tool capable of real-time monitoring and simultaneously quantifying of both intra/extracellular chemical signals across the large-scale brain is the key bottleneck for understanding the interactions between the molecules inside and outside neurons. Here we built up a high-density intra/extracellular optophysiology platform, together with developing two probes for specific recognition of L-cysteine (Cys) and dopamine (DA), for simultaneously quantifying of both intracellular Cys and extracellular DA with high selectivity and accuracy across the brain of freely moving animals, as well as recording electrical signals. Using this powerful tool, it was found that intracellular Cys regulated extracellular DA through inducing the expression of tyrosine hydroxylase in the depressed mice brain. We also established the functional networks of Cys and DA across 32 brain regions in freely moving animals. More importantly, it was discovered that depression reduced the correlations between adjacent brain regions, which was recovered by the treatment of N-acetyl-l-cysteine.