Correction to "ß-Phase Crystallinity, Printability, and Piezoelectric Characteristics of Polyvinylidene Fluoride (PVDF)/Poly(methyl methacrylate) (PMMA)/Cyclopentyl-polyhedral Oligomeric Silsesquioxane (Cp-POSS) Melt-Compounded Blends".

[This corrects the article DOI: 10.1021/acsapm.4c00468.].

Reprocessable Networks from Vegetable Oils, Salts, and Food Acids: A Green Polymer Outreach Demonstration for Middle School Students.

Massive amounts of mismanaged plastic waste have led to growing concerns about their adverse impacts on the environment, ecosystem, and human health. Enabling efficient plastic recycling is a key component for developing a sustainable future, which requires cohesive efforts in technology innovations, public awareness, and workforce development. Particularly, outreach activities to inform the broader community about current efforts to fabricate sustainable polymeric materials can play a central role in inspiring future generations while also improving their knowledge, viewpoints, and behaviors to address plastic waste challenges. Herein, this account demonstrates an effort to educate middle school students about a key emerging concept in polymer science for sustainable material development: reprocessable polymer networks. Background information is provided to the students about the need to transition from petroleum-based chemical feedstocks to their bioderived counterparts. We note that the materials used in this demonstration lesson are all produced from common household foods, with which students routinely interact in various applications, making them not only safe but also compelling for the middle school classroom.

ß-Phase Crystallinity, Printability, and Piezoelectric Characteristics of Polyvinylidene Fluoride (PVDF)/Poly(methyl methacrylate) (PMMA)/Cyclopentyl-Polyhedral Oligomeric Silsesquioxane (Cp-POSS) Melt-Compounded Blends.

Poly(vinylidene fluoride) (PVDF) is a semicrystalline polymer that exhibits unique piezoelectric characteristics along with good chemical resistance and high thermal stability. Layer-based material extrusion (MEX) 3D printing of PVDF is desired to create complex structures with piezoelectric properties; however, the melt processing of PVDF typically directs the formation of the α crystalline allomorph, which does not contribute to the piezoelectric response. In this work, PVDF was compounded with poly(methyl methacrylate) (PMMA) and cyclopentyl-polyhedral oligomeric silsesquioxane (Cp-POSS) nanostructured additives in binary and ternary blends to improve MEX printability while maintaining piezoelectric performance. Overall crystallinity and ß phase content were evaluated and quantified using a combination of attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and differential scanning calorimetry (DSC). Enhancement of MEX printability was measured by quantifying the interlayer adhesion and warpage of printed parts. All blends studied contained a significant percentage of ß allomorph, but it could be detected by ATR-FTIR only after the removal of a thin surface layer. Inclusion of 1% Cp-POSS and up to 10% PMMA in blends with PVDF improved interlayer adhesion (2.3-3.6x) and lowered warpage of MEX printed parts compared to neat PVDF. The blend of 1% Cp-POSS/1% PMMA/PVDF was demonstrated to significantly improve the quality of MEX printed parts while showing similar piezoelectric performance to that of neat PVDF (average piezoelectric coefficient 24 pC/N). MEX printing of PVDF blends directly into usable parts with significant piezoelectric performance while reducing the challenges of printing the semicrystalline polymer opens the potential for application in a number of high value sectors.

Mito-Specific Nutri-Hijacker Synergizing Mitochondrial Metabolism and Glycolysis Intervention for Enhanced Antitumor Bioenergetic Therapy.

Metabolic rewiring, a dynamic metabolic phenotype switch, confers that tumors exist and proliferate after fitness (or preadaptation) in harsh environmental conditions. Glycolysis deprivation was considered to be a tumor's metabolic Achilles heel. However, metabolic configuration can flexibly retune the mitochondrial metabolic ability when glycolysis is scared, potentially resulting in more aggressive clones. To address the challenge of mitochondrial reprogramming, an antiglycolytic nanoparticle (GRPP NP) containing a novel mitochondrial-targeted reactive oxygen species (ROS) generator (diIR780) was prepared to hijack glucose and regulate mitochondria, thus completely eliminating tumorigenic energy sources. In this process, GRPP NPs@diIR780 can catalyze endogenous glucose, leading to significantly suppressed glycolysis. Moreover, diIR780 can be released and selectively accumulated around mitochondria to generate toxic ROS. These combined effects, in turn, can hamper mitochondrial metabolism pathways, which are crucial for driving tumor progression. This synchronous intervention strategy enables utter devastation of metabolic rewiring, providing a promising regiment to eradicate tumor lesions without recurrence.

Research Experiences via Integrating Simulations and Experiments (REVISE): A Model Collaborative Research Project for Undergraduate Students in CO2 Sorbent Design.

Undergraduate research experiences are an instrumental component of student development, increasing conceptual understanding, promoting inquiry-based learning, and guiding potential career aspirations. Moving one step further, as research continues to become more interdisciplinary, there exists potential to accelerate student growth by granting additional perspectives through collaborative research. This study demonstrates the utilization of a model collaborative research project, specifically investigating the development of sorbent technologies for efficient CO2 capture, which is an important research area for improving environmental sustainability. A model CO2 sorbent system of heteroatom-doped porous carbon is utilized to enable students to gain knowledge of adsorption processes, through combined experimental and computational investigations and learnings. A particular emphasis is placed on creating interdisciplinary learning experiences, exemplified by using density functional theory (DFT) to understand molecular interactions between doped carbon surfaces and CO2 molecules as well as explain underlying physical mechanisms that govern experimental results. The experimental observations about CO2 sorption performance of doped ordered mesoporous carbons (OMCs) can be correlated with simulation results, which can explain how the presence of heteroatom functional groups impact the ability of porous carbon to selectively adsorb CO2 molecules. Through an inquiry-focused approach, students were observed to couple interdisciplinary results to construct holistic explanations, while developing skills in independent research and scientific communications. This collaborative research project allows students to obtain a deeper understanding of sustainability challenges, cultivate confidence in independent research, prepare for future career paths, and most importantly, be exposed to strategies employing interdisciplinary research approaches to address scientific challenges.

Accurate additive manufacturing of lightweight and elastic carbons using plastic precursors.

Despite groundbreaking advances in the additive manufacturing of polymers, metals, and ceramics, scaled and accurate production of structured carbons remains largely underdeveloped. This work reports a simple method to produce complex carbon materials with very low dimensional shrinkage from printed to carbonized state (less than 4%), using commercially available polypropylene precursors and a fused filament fabrication-based process. The control of macrostructural retention is enabled by the inclusion of fiber fillers regardless of the crosslinking degree of the polypropylene matrix, providing a significant advantage to directly control the density, porosity, and mechanical properties of 3D printed carbons. Using the same printed plastic precursors, different mechanical responses of derived carbons can be obtained, notably from stiff to highly compressible. This report harnesses the power of additive manufacturing for producing carbons with accurately controlled structure and properties, while enabling great opportunities for various applications.

Immobilization of Protease K with ZIF-8 for Enhanced Stability in Polylactic Acid Melt Processing and Catalytic Degradation.

Polylactic acid (PLA) is a biodegradable alternative to petroleum-based polymers for improving environmental sustainability of our society. However, the limited degradation rate and environmental conditions for PLA-based products remain significant challenges for their broader use in various applications. While Proteinase K (Pro K) from Tritirachium album has been demonstrated to efficiently degrade PLA, its autocatalytic degradation function in composite films is underexplored. Here, this work reports a strategy that encapsulates Pro K with zeolitic imidazole framework-8 (ZIF-8) in situ, combining a PLA matrix to prepare Pro K@ZIF-8/PLA films through solvent casting. The method is scalable and commercially viable, and the pH and thermal stability of the Pro K enzyme are significantly enhanced after immobilization. The enzyme can retain 61.8% of its initial activity after annealing at 160 °C for 10 min, allowing for its use in the melt processing of filler-containing PLA films. As a result, Pro K@ZIF-8/PLA films in buffer solutions exhibit stable degradation rates, which can be extended to PLA decomposition in acidic environments. Moreover, the enzyme in Pro K@ZIF-8/PLA films prepared by thermoforming remains active sufficiently to degrade PLA with a weight loss of up to 15% in 2 weeks. These results further indicate that our strategy can be broadly applicable for melt processing and controlled degradation of PLA materials with immobilized enzymes, allowing for its transformative impact for promoting environmental sustainability.

Dry-Processable Polymer Electrolytes for Solid Manufactured Batteries.

Designing a solid-state electrolyte that satisfies the operating requirements of solid-state batteries is key to solid-state battery applications. The consensus is that solid-state electrolytes need to allow fast ion transport, while providing better interfacial compatibility and mechanical tolerance. Herein, a simple but effective strategy is proposed, combining hard and soft component polymer systems, to exploit a solid polymer electrolyte (SPE) with a 3D network via an in situ graft polymerization. The 3D structure is constructed by a hard cellulose nanocrystal (CNC) as the skeleton and a soft polyacrylonitrile (PAN) as the filler through a dry-processing method. The reported systems have several advantages, including ease of processing, only requiring using an exceedingly small amount of solvent, light weight (ρ = 1.2 g cm-3), excellent mechanical stability (tensile strength of 9.5 MPa), and high ionic conductivity (3.9 × 10-4 S cm-1, 18 °C) and migration number (tLi+ = 0.8). In particular, the high conductivity is enabled: the efficient Li+ transportation path constructed between CNC-PAN powders and abundant sulfonate radicals and hydroxyl groups on the CNC surface acts as the bridge of Li+ transition. When the CNCs are grafted onto the PAN polymer, the dipole-dipole interaction between the nitrile groups of the PAN and the hydroxyl groups of the CNCs can help to improve the mechanical stability and ionic conductivity of the SPE. Moreover, a tightly formed interface between SPE and LiFePO4 (LFP)/carbon black/SPE cathode can be achieved in an assembled solid-state battery by hot pressing, thus further enhancing the battery's performance.

Correction: A generalized method for alignment of block copolymer films: solvent vapor annealing with soft shear.

Correction for 'A generalized method for alignment of block copolymer films: solvent vapor annealing with soft shear' by Zhe Qiang et al., Soft Matter, 2014, 10, 6068-6076, https://doi.org/10.1039/C4SM00875H.

HBx induced upregulation of FATP2 promotes the development of hepatic lipid accumulation.

The hepatitis B Virus X (HBx) protein plays a crucial role in the HBV-induced hepatic steatosis. Fatty acid transport protein 2 (FATP2) is a key protein that is involved in hepatic lipogenesis, and it was found to be highly expressed in various metabolic diseases. However, Whether FATP2 is a key factor in the pathogenesis of HBx-induced hepatic steatosis remains unclear. In this study, we found that FATP2 was up-regulated by HBx in vitro and in vivo and participated in HBx-induced hepatic lipid accumulation. Treatment of HBx-expressing cell lines and mice with FATP2 inhibitor (FATP2i) lipofermata ameliorated HBx-induced lipid accumulation and reduced oxidative stress and inflammation caused by lipid accumulation. Moreover, the liver injury of mouse was restored after FATP2i treatment. In summary, our results reveal that FATP2 is a key driver factor for HBx-induced hepatic lipid accumulation, and inhibition of FATP2 can ameliorates lipid accumulation caused by HBx. This study provides new insights into the mechanism of HBV-induced hepatic steatosis.

Human embryonic stem cells exert antitumor effects on prostate cancer cells in a co-culture microenvironment.

Prostate cancer is currently the most common malignancy among men. Given the limitations of current conventional anticancer therapies, new high-risk treatments are urgently needed. Previous studies have shown that embryonic stem cells (ESCs) can reverse the tumorigenic phenotype of tumor cells. However, there are still challenges in using human ESCs (hESCs) directly in cancer treatment. To facilitate the practical application of hESCs, we established a co-culture system consisting of prostate cancer cell lines and hESCs and investigated the antitumor activity of the supernatant of the co-culture system (Co-Sp) in vitro and in vivo, as well as the underlying mechanisms involved. The Co-Sp decreased the viability of prostate cancer cells in a concentration-dependent manner, significantly inhibited colony formation, and induced cell cycle arrest at the G0/G1 phase of the cell cycle. In addition, Co-Sp promoted apoptosis of prostate cancer cells and inhibited cell migration and invasion. In vivo studies also revealed that Co-Sp inhibited tumor growth in the xenograft model. Mechanistic studies showed that Co-Sp reduced the expression of cyclin D1, cyclin E, CDK4, CDK2, MMP-9, MMP-1, and Bcl-2, and increased the expression of p21, cleaved caspase-9, cleaved caspase-3, cleaved PARP, and Bax in prostate cancer cells. Furthermore, the Co-Sp decreased the phosphorylation of PI3K, AKT, and mTOR in cells and tumor tissues. Taken together, our results indicated that the Co-Sp has potent antitumor activity and could directly inhibit tumor growth. Our findings provide a new and effective way for the application of hESCs in cancer therapy and contribute to a new strategy for clinical stem cell therapy.

Accelerated Synthesis of Ordered Mesoporous Carbons Using Plasma.

Conventional ordered mesoporous carbon (OMC) production usually requires long processing times in the carbonization step to achieve desired temperatures through controlled ramps. To enable expedited materials discovery, developing advanced manufacturing capability with significantly improved throughput is highly desired. Current approaches for accelerating the synthesis of OMCs include using microwave and Joule heating. However, both methods rely on the introduction of additional components, such as microwave absorbers and electrically conductive agents, within the bulk materials to impart the ability to reach high carbonization temperatures. This work demonstrates accelerated synthesis and functionalization of OMCs through the use of a dielectric barrier discharge plasma, where carbonization can be accomplished within 15 min using 30 W plasma sources, representing more than an order of magnitude increase in polymer-to-carbon conversion kinetics compared to that of a traditionally pyrolyzed analogue. Particularly, the ability of performing rapid carbonization without the use of additional substrates within the OMC precursor systems is advantageous. A systematic investigation of how plasma power, time, and gas atmosphere impact the resulting OMC pore textures and properties is performed, demonstrating the broad applicability of plasma-enabled carbonization methods. Furthermore, we demonstrate that the plasma treatment strategy can be extended to incorporate heteroatoms into the carbon framework by introducing ammonia gas, resulting in OMCs with a nitrogen content up to 4.7 at %, as well as non-Pluronic templating systems for synthesizing OMC with pore sizes larger than 10 nm. As employing a plasma source for materials pyrolysis is an industrially relevant approach, our system can be extended toward scaled synthesis of OMCs with much faster production rates.

Cuproptosis-related molecular subtypes direct T cell exhaustion phenotypes and therapeutic strategies for patients with lung adenocarcinoma.

Background: T cell exhaustion (TEX) heterogeneity leads to unfavorable immunotherapeutic responses in patients with cancer. Classification of TEX molecular phenotypes is pivotal to overcoming TEX and improving immunotherapies in the clinical setting. Cuproptosis is a novel form of programmed cell death associated with tumor progression. However, the relation between cuproptosis-related genes (CuRGs) and the different TEX phenotypes has not been investigated in lung adenocarcinoma (LUAD). Methods: Unsupervised hierarchical clustering and principal component analysis (PCA) algorithm were performed to determine CuRGs-related molecular subtypes and scores for patients with LUAD. The tumor immune microenvironment (TIME) landscape in these molecular subtypes and scores was estimated using ESTIMATE and ssGSEA algorithms. Furthermore, TEX characteristics and phenotypes were evaluated in distinct molecular subtypes and scores through GSVA and Spearman correlation analysis. Finally, TIDE scores, immunophenoscore, pRRophetic, GSE78220, and IMvigor210 datasets were employed to appraise the distinguishing capacity of CuRGscore in immunotherapy and pharmacotherapy effectiveness. Results: We identified three CuRGclusters, three geneClusters, and CuRGscore based on 1012 LUAD transcriptional profiles from five datasets. Compared with other molecular subtypes, CuRGcluster B, geneCluster C, and low-CuRGscore group with good prognosis presented fewer TEX characteristics, including immunosuppressive cells infiltration and TEX-associated gene signatures, signal pathways, checkpoint genes, transcription and inflammatory factors. These molecular subtypes were also responsive in distinguishing TEX phenotype in the terminal, GZMK+, and OXPHOS- TEX subtypes, but not the TCF7+ TEX subtype. Notably, copper importer and exporter, SLC31A1 and ATP7B, were remarkably associated with four TEX phenotypes and nine checkpoint genes such as PDCD1, CTLA4, HAVCR2, TIGIT, LAG3, IDO1, SIGLEC7, CD274, PDCD1LG2, indicating that cuproptosis was involved in the development of TEX and immunosuppressive environment in patients with LUAD. Moreover, CuRGscore was significantly related to the TIDE score, immunophenoscore, and terminal TEX score (Spearman R = 0.62, p < 0.001) to effectively predict immunotherapy and drug sensitivity in both training and external validation cohorts. Conclusion: Our study demonstrated the extensive effect of cuproptosis on TEX. CuRGs-related molecular subtypes and scores could illuminate the heterogeneity of TEX phenotype as reliable tools in predicting prognosis and directing more effective immunotherapeutic and chemotherapeutic strategies for patients with LUAD.

Direct Measurement of Polymer-Chain-End-to-End Distances by Using RAFT Chain Transfer Agent as the FRET Acceptor.

Förster resonance energy transfer (FRET) is a powerful tool for measuring distances between two molecules (donor and acceptor) in close proximity (1-10 nm), which can be employed for determining polymer end-to-end distances (Ree). However, previous works for labeling FRET pairs on chain-ends often involve relatively complex steps for materials preparation, potentially limiting their broad use in synthetic polymer systems. In this work, we introduce an anthracene-functionalized chain-transfer agent for reversible addition-fragmentation chain-transfer (RAFT) polymerizations, which can directly yield polymers containing FRET donor and acceptor molecules on respective chain-ends. This approach enables the direct use of FRET for characterizing the averaged Ree of polymers. Building on this platform, we investigate the averaged Ree of polystyrene (PS) and poly(methyl methacrylate) (PMMA) in a good solvent as a function of their molecular weight. Notably, the FRET results show good agreement with simulation results obtained from all-atom molecular dynamics, confirming its measurement accuracy. Overall, this work provides a facile and broadly applicable platform to directly determine the Ree of low molecular weight polymers by using FRET-based methods.

Direct synthesis of ordered mesoporous materials from thermoplastic elastomers.

The ability to manufacture ordered mesoporous materials using low-cost precursors and scalable processes is essential for unlocking their enormous potential to enable advancement in nanotechnology. While templating-based methods play a central role in the development of mesoporous materials, several limitations exist in conventional system design, including cost, volatile solvent consumption, and attainable pore sizes from commercial templating agents. This work pioneers a new manufacturing platform for producing ordered mesoporous materials through direct pyrolysis of crosslinked thermoplastic elastomer-based block copolymers. Specifically, olefinic majority phases are selectively crosslinked through sulfonation reactions and subsequently converted to carbon, while the minority block can be decomposed to form ordered mesopores. We demonstrate that this process can be extended to different polymer precursors for synthesizing mesoporous polymer, carbon, and silica. Furthermore, the obtained carbons possess large mesopores, sulfur-doped carbon framework, with tailorable pore textures upon varying the precursor identities.

Additive Manufacturing of Carbon Using Commodity Polypropylene.

Carbon materials are essential to the development of modern society with indispensable use in various applications, such as energy storage and high-performance composites. Despite great progress, on-demand carbon manufacturing with control over 3D macroscopic configuration is still an intractable challenge, hindering their direct use in many areas requiring structured materials and products. This work introduces a simple and scalable method to generate complex, large-scale carbon structures using easily accessible materials and technologies. 3D-printed, commercial polypropylene (PP) parts can be thermally stabilized through cracking-facilitated diffusion and crosslinking. The newly elucidated mechanism from this work allows thick PP parts to yield carbonaceous products with complex structures through a subsequent pyrolysis step. The approach for enabling PP-to-carbon conversion has consistent product yield and controlled dimensional shrinkage. Under optimized processing conditions, these PP-derived carbons exhibit robust mechanical properties and excellent joule heating performance, demonstrated by their versatile use as heating elements. Furthermore, this process can be extended to recycled PP, enabling the conversion of waste plastic materials to value-added products. This work provides an innovative approach to create structured carbon materials with direct access to complex geometry, which can be transformative to, and broadly benefit, many important technological applications.

Mechanically Strong, Freeze-Resistant, and Ionically Conductive Organohydrogels for Flexible Strain Sensors and Batteries.

Conductive hydrogels as promising material candidates for soft electronics have been rapidly developed in recent years. However, the low ionic conductivity, limited mechanical properties, and insufficient freeze-resistance greatly limit their applications for flexible and wearable electronics. Herein, aramid nanofiber (ANF)-reinforced poly(vinyl alcohol) (PVA) organohydrogels containing dimethyl sulfoxide (DMSO)/H2 O mixed solvents with outstanding freeze-resistance are fabricated through solution casting and 3D printing methods. The organohydrogels show both high tensile strength and toughness due to the synergistic effect of ANFs and DMSO in the system, which promotes PVA crystallization and intermolecular hydrogen bonding interactions between PVA molecules as well as ANFs and PVA, confirmed by a suite of characterization and molecular dynamics simulations. The organohydrogels also exhibit ultrahigh ionic conductivity, ranging from 1.1 to 34.3 S m-1 at -50 to 60 °C. Building on these excellent material properties, the organohydrogel-based strain sensors and solid-state zinc-air batteries (ZABs) are fabricated, which have a broad working temperature range. Particularly, the ZABs not only exhibit high specific capacity (262 mAh g-1 ) with ultra-long cycling life (355 cycles, 118 h) even at -30 °C, but also can work properly under various deformation states, manifesting their great potential applications in soft robotics and wearable electronics.

The Different Prognoses of Hepatocellular Carcinoma with Previous Tenofovir versus Entecavir Treatment for Chronic Hepatitis B Virus: Analysis Based on 15 Propensity Score-Matched Studies.

BACKGROUND: Currently, enough studies with aggregated study-level data have demonstrated that there was no clinically meaningful difference in the risk of hepatocellular carcinoma (HCC) between patients who received entecavir and patients who received tenofovir treatment for chronic hepatitis B virus (CHBV). However, many studies found many differences in prognosis of these HCC patients. This meta-analysis of high-quality propensity score-matched (PSM) studies was designed to provide robust estimates for comparative HCC prognosis between groups receiving tenofovir or entecavir. METHODS: PubMed, Embase, Cochrane Library, and Web of Science were searched from inception to July 10, 2022, for relevant studies that compare the different prognoses of HCC between tenofovir and entecavir treatment. The primary outcomes were the difference of overall death or liver transplantation between tenofovir and entecavir treatment. The secondary outcomes included risk factors of overall death or liver transplantation and different treatment responses between tenofovir and entecavir treatment for CHBV. All statistical analyses were performed using the standard statistical procedures provided in Review Manager 5.2. RESULTS: A total of 15 PSM studies were identified, with 24,035 sample sizes in tenofovir group and 61,410 sample sizes in entecavir group, respectively. Pooled data indicated that, compared with entecavir, patients receiving tenofovir experienced significantly lower overall death or liver transplantation, with a pooled OR of 0.55 (95% CI: 0.45-0.68; p < 0.00001). Subgroup analysis by population also found similar results with pooled ORs of 0.52 (95% CI: 0.38-0.70; p < 0.0001) in entire cohort and 0.62 (95% CI: 0.50-0.77; p < 0.0001) in PSM cohort. Similarly, the subgroup analysis also found that HCC patients without cirrhosis receiving tenofovir experienced significantly lower overall death or liver transplantation than entecavir (OR: 0.56; 95% CI: 0.49-0.66), but no significant result was found in HCC patients with cirrhosis. In addition, both univariate (OR: 0.46; 95% CI: 0.31-0.69) and multivariable analyses (OR: 0.86; 95% CI: 0.82-0.91) also indicated significant reduction of overall death or liver transplantation in tenofovir group than entecavir group. CONCLUSION: Our analysis indicated that there was clinically meaningful difference in prognosis of HCC between patients who received entecavir and patients who received tenofovir. Patients who received tenofovir experienced much lower overall death or liver transplantation than patients who received entecavir. Tenofovir treatment may be one of independent favorable factors of prognosis for HCC patients with CHBV.

Organelle-targeted therapies: a comprehensive review on system design for enabling precision oncology.

Cancer is a major threat to human health. Among various treatment methods, precision therapy has received significant attention since the inception, due to its ability to efficiently inhibit tumor growth, while curtailing common shortcomings from conventional cancer treatment, leading towards enhanced survival rates. Particularly, organelle-targeted strategies enable precise accumulation of therapeutic agents in organelles, locally triggering organelle-mediated cell death signals which can greatly reduce the therapeutic threshold dosage and minimize side-effects. In this review, we comprehensively discuss history and recent advances in targeted therapies on organelles, specifically including nucleus, mitochondria, lysosomes and endoplasmic reticulum, while focusing on organelle structures, organelle-mediated cell death signal pathways, and design guidelines of organelle-targeted nanomedicines based on intervention mechanisms. Furthermore, a perspective on future research and clinical opportunities and potential challenges in precision oncology is presented. Through demonstrating recent developments in organelle-targeted therapies, we believe this article can further stimulate broader interests in multidisciplinary research and technology development for enabling advanced organelle-targeted nanomedicines and their corresponding clinic translations.

Linear ubiquitination of PTEN impairs its function to promote prostate cancer progression.

PTEN is frequently mutated in human cancers, which leads to the excessive activation of PI3K/AKT signaling and thus promotes tumorigenesis and drug resistance. Met1-linked ubiquitination (M1-Ubi) is also involved in cancer progression, but the mechanism is poorly defined. Here we find that HOIP, one important component of linear ubiquitin chain assembly complex (LUBAC), promotes prostate cancer (PCa) progression by enhancing AKT signaling in a PTEN-dependent manner. Mechanistically, PTEN is modified by M1-Ubi at two sites K144 and K197, which significantly inhibits PTEN phosphatase activity and thus accelerates PCa progression. More importantly, we identify that the high-frequency mutants PTENR173H and PTENR173C in PCa patients showed the enhanced level of M1-Ubi, which impairs PTEN function in inhibition of AKT phosphorylation and cell growth. We also find that HOIP depletion sensitizes PCa cells to therapeutic agents BKM120 and Enzalutamide. Furthermore, the clinical data analyses confirm that HOIP is upregulated and positively correlated with AKT activation in PCa patient specimen, which may promote PCa progression and increase the risk of PCa biochemical relapse. Together, our study reveals a key role of PTEN M1-Ubi in regulation of AKT activation and PCa progression, which may propose a new strategy for PCa therapy.