Marital status impacts survival of stage I non-small-cell lung cancer: a propensity-score matching analysis.

Aim: This population-based analysis aimed to explore the associations among marital status, prognosis and treatment of stage I non-small-cell lung cancer. Materials & methods: The propensity score matching (PSM), logistic regression and Cox proportional hazards model were used in this study. Results: A total of 13,937 patients were included. After PSM, 10579 patients were co-insured. The married were more likely to receive surgical treatment compared with the unmarried patients (OR: 1.841, p < 0.001), and patients who underwent surgery also tended to have better survival (HR: 0.293, p < 0.001). Conclusion: Compared with unmarried patients, a married group with stage I NSCLC had timely treatment and more satisfactory survival. This study highlights the importance of prompt help and care for unmarried patients.

An ALP-responsive, anionic iridium complex for specific recognition of osteosarcoma cells.

Poor cellular permeability greatly hampers the utilization of anionic Ir(III) complexes, though efficiently emissive and remarkably stable, in cell-based diagnosis. To overcome this barrier, we present the development of an alkaline phosphatase (ALP)-responsive, anionic, and aggregation-induced emission (AIE)-active Ir(III) complex (Ir1) for specific recognition of osteosarcoma cells. Containing phosphate moieties, Ir1 exhibits a net -1 charge, enabling charge repulsion from the cell membrane and resulting in low cellular uptake and good biocompatibility in normal osteoblast cells. Upon ALP-mediated hydrolysis of phosphate groups, the resulting dephosphorylated product, Ir2, demonstrates a positive charge and increased lipophilicity, promoting cellular uptake and activating its AIE properties for specific recognition of osteosarcoma cells that express elevated levels of ALP. This study elucidates the role of ALP as an ideal trigger for enhancing the cellular permeability of phosphate ester-containing Ir(III) complexes, thus expanding the potential of anionic Ir(III) complexes for biomedical applications.

Acid-assisted self-assembly of pyrene-capped tyrosine ruptures lysosomes to induce cancer cell apoptosis.

Induced lysosomal membrane permeabilization (LMP) by peptide self-assembly has emerged as an effective platform for lysosome-targeted cancer therapy. In this study, we shift this strategical paradigm and present an innovative approach to LMP induction through amino acid-based self-assembly. Pyrene-capped tyrosine (Py-Tyr), as a proof-of-concept molecule, is designed with acidity-responsive self-assembly. Under acidic conditions (pH 4), Py-Tyr is protonated with reduced charge repulsion, and self-assembles into micrometer-scaled aggregates, which exceed the biological size of lysosomes. Cell experiments showed that Py-Tyr specifically accumulates in lysosomes and induces lysosome rupture, leading to the release of cathepsin B into the cytoplasm for subsequent apoptosis activation in cancer cells. This study capitalizes on the concept of amino acid assembly for efficient LMP induction, providing a simple and versatile platform for precise and effective therapeutic interventions in cancer therapy.

Self-Assembly of Sulfate-Containing Peptides Sequesters VEGF for Inhibiting Cancer Cell Invasion.

Heparan sulfate proteoglycans (HSPGs) play a crucial role in regulating cancer growth and migration by mediating interactions with growth factors. In this study, we developed a self-assembling peptide (S1) containing a sulfate group to simulate the contiguous sulfated regions (S-domains) in heparan sulfate for growth factor binding, aiming to sequester growth factors like VEGF. Spectral and structural studies as well as simulation studies suggested that S1 self-assembled into nanostructures similar to the heparan sulfate chains and effectively bound to VEGF. On cancer cell surfaces, S1 self-assemblies sequestered VEGF, leading to a reduction in VEGF levels in the medium, consequently inhibiting cancer cell growth, invasion, and angiogenesis. This study highlights the potential of self-assembling peptides to emulate extracellular matrix functions, offering insights for future cancer therapeutic strategies.

Smoking Behavior and its Effect on Psychiatric Symptoms of Patients with Stable Schizophrenia.

Context: Schizophrenia is a common and clinically disabling mental disorder. Many patients with schizophrenia smoke. Research on the effects of smoking on schizophrenia's symptoms are inconsistent. Objective: The study intended to investigate the smoking status of patients with stable schizophrenia to determine the effects of smoking on schizophrenia-related symptoms. Design: The research team performed an case-control study. Setting: The study took place at Beijing Huilongguan Hospital in Beijing, Changping District, China. Participants: Participants were 160 patients at the hospital who had been diagnosed with stable schizophrenia between April 2018 and March 2020. Groups: The research team divided participants into two groups based on their current smoking status: (1) a smoking group with 72 participants and (2) a nonsmoking group with 88 participants. Outcome Measures: The research team: (1) examined the types of antipsychotic drugs that participants received; (2) used a schizophrenia-related scale, the Positive and Negative Syndrome Scale (PANSS), to examine participants' status; (3) examined the smoking habits of the smoking group; and (4) analyzed the correlation between the PANSS score and the smoking group's smoking index. Results: No significant difference existed between the groups in the type of medicine used (P > .05). The smoking group's PANSS total (P = .014), positive symptom (P = .039), and negative symptom (P = .003) scores were significantly lower than those of the nonsmoking group (P < .05). No significant difference existed between the groups in the general psychopathological symptom score (P > .05). The smoking group started smoking between 13 and 24 years of age, with an mean age of 19.11 ± 4.10 years. The group smoked 10-30 cigarettes/d, with a mean smoking amount of 18.4 ± 3.1 cigarettes/d, and the smoking index was 344.7 ± 48.0. The smoking group's smoking index was significantly negatively correlated with the positive symptom, negative symptom, and total PANSS scores (all P = .000). No correlation existed between the smoking index and the general psychopathological symptom score (P > .05). Conclusions: Smoking patients with stable schizophrenia generally exhibit fewer symptoms than nonsmoking patients, which relate to the alleviation of mental tension that smoking can provide.

Discovery of 6-Acylamino/Sulfonamido Benzoxazolone with IL-6 Inhibitory Activity as Promising Therapeutic Agents for Ulcerative Colitis.

Ulcerative colitis has been widely concerned for its persistent upward trend, and the sustained overproduction of pro-inflammatory cytokines such as IL-6 remains a crucial factor in the development of UC. Therefore, the identification of new effective drugs to block inflammatory responses is an urgent and viable therapeutic strategy for UC. In our research, twenty-three 6-acylamino/sulfonamido benzoxazolone derivatives were synthesized, characterized, and evaluated for anti-inflammatory activity against NO and IL-6 production in LPS-induced RAW264.7 cells. The results demonstrated that most of the target compounds were capable of reducing the overexpression of NO and IL-6 to a certain degree. For the most active compounds 3i, 3j and 3 l, the inhibitory activities were superior or equivalent to those of the positive drug celecoxib with a dose-dependent relationship. Furthermore, animal experiments revealed that active derivatives 3i, 3j and 3 l exhibited definitive therapeutical effect on DSS induced ulcerative colitis in mice by mitigating weight loss and DAI score while decreasing levels of pro-inflammatory cytokines such as IL-6 and IFN-γ, simultaneously increasing production of anti-inflammatory cytokines IL-10. In addition, compounds 3i, 3j and 3 l could also inhibit the oxidative stress to alleviate ulcerative colitis by decreasing MDA and MPO levels. These finding demonstrated that compounds 3i, 3j and 3 l hold significant potential as novel therapeutic agents for ulcerative colitis.

New sesquiterpenoids with neuroprotective effects in vitro and in vivo from the Picrasma chinensis.

Three undescribed sesquiterpenes, designed as pichinenoid A-C (1-3), along with nine known ones (4-12) were isolated from the stems and leaves of Picrasma chinensis. The new isolates including their absolute configurations were elucidated based on extensive spectroscopic methods, single crystal X-ray diffraction, and electronic circular dichroism (ECD) experiments, as well as comparison with literature data. Structurally, compounds 1 and 2 are descending sesquiterpenes, while pichinenoid C (3) is a rare sesquiterpene bearing a 2-methylenebut-3-enoic acid moiety at the C-6 side chain. All the isolated compounds were tested for their neuroprotective effects against the H2O2-induced damage on human neuroblastoma SH-SY5Y cells, and most of them showed moderate neuroprotective activity. Especially, compounds 1, 3-5, and 7 showed a potent neuroprotective effect at 25 or 50 µM. Moreover, the neuroprotective effects of compounds 1 and 4 were tested on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model. Results of western blot and immunofluorescence indicated that compound 4 significantly counteract the toxicity of MPTP, and reversed the expression of tyrosine hydroxylase (TH) in substantia nigra (SN) and striatum (ST) of the mouse brain. Interestingly, western blot data suggested compound 4 also enhanced B-cell lymphoma-2 (Bcl-2) and heme oxygenase 1 (HO-1) expressions in the brain tissues from MPTP damaged mouse.

Dynamic Oscillation and Motion of Oil-in-Water Emulsion Droplets.

The interplay of interfacial tensions on droplets results in a range of self-powered motions that mimic those of living systems and serve as a tunable model to understand their complex non-equilibrium behavior. Spontaneous shape deformations and oscillations are crucial features observed in nature but difficult to incorporate in synthetic artificial systems. Here, we report sessile oil-in-water emulsions that exhibit rapid oscillating behavior. The oscillations depend on the nature and concentration of the surfactant, the chemical composition of the oil, and the wettability of the solid substrate. The rapid changes in the contact angle per oscillation are observed using side-view optical microscopy. We propose that the changes in the interfacial tension of the oil droplets is due to the partitioning of the surfactant into the oil phase and the movement of self-emulsified oil out of the parent droplets giving rise to the rhythmic variation in droplet contact-line. The ability to control and understand droplet oscillation can help model similar oscillations in out-of-equilibrium systems in nature and reproduce biomimetic behavior in artificial systems for various applications, such as microfluidic lab-on-a-chip and adaptive materials.

Mechanism of Intestinal Epithelial Absorption and Electrophysiological Regulation of the Shrimp Peptide QMDDQ.

We investigated the absorption mechanism of the shrimp peptide QMDDQ in small intestines, explored its physiological function in inhibiting neuronal hyperactivity, and verified its entry into the brain in vivo to display functional activity. The everted rat sac model and a Caco-2 paracellular absorption monolayer model were used, indicating that QMDDQ has a good absorption capacity with an apparent permeability coefficient (Papp) > 1 × 10-6 cm/s and the absorption of QMDDQ was concentration-dependent. When the concentration of QMDDQ was 1 mM and the transport time was 180 min, the highest absorption concentration of QMDDQ was 41.17 ± 3.48 µM (P < 0.05). The myosin light-chain kinase (MLCK)-specific inhibitor ML-7 and activator MPA, Western blotting, and immunofluorescence results showed that QMDDQ absorption takes place by mediating the MLCK-p-MLCK-MLC signaling pathway, reversibly opening the zonula occludens-1 (ZO-1), occludin in tight junctions (TJs), upregulating claudin-2 expression, and reaching targets through blood to inhibit neuronal overactivity. Results of fluorescence imaging in vivo verified that QMDDQ could enter the brain 4 h after oral administration. The results provide a theoretical foundation for the mechanism of paracellular absorption of active peptides and a starting point for the development of functional foods for Alzheimer's disease intervention.

Tinopanoids K-T, clerodane diterpenoids with anti-inflammatory activity from Tinospora crispa.

A total of 17 structurally diverse clerodane diterpenoids, including ten undescribed clerodane diterpenoids (tinopanoids K-T, 1-10) and seven known compounds (11-17), were isolated from the vines and leaves of Tinospora crispa. Compound 3 has not only bear the dominant substituents of γ-hydroxy-α, ß-unsaturated-γ-lactone with anti-inflammatory activity, but also a ternary epoxy structure at C-3/C-4. The planar structures and relative configurations of the clerodane diterpenoids were elucidated by spectroscopic data interpretation. The absolute configurations of compounds 1, 4, 8 and 13 were determined by single-crystal X-ray crystallographic, while that of compound 3 was determined using computed ECD data and single crystal X-ray diffraction of related p-bromobenzoate ester (3a). Subsequently, all compounds were evaluated for their inhibitory effect on nitric oxide (NO) production of LPS-activated BV-2 cells, and compounds 3 and 8 exhibited better NO inhibitory potency, with IC50 values of 5.6 and 13.8 µM than the positive control minocycline (Mino, IC50 = 22.9 µM). The corresponding results of western blot analysis and qRT-PCR revealed that compound 3 can significantly inhibit the inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) protein expressions, mRNA levels of pro-inflammatory cytokins of tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6) and interleukin 1ß (IL-1ß). The underlying mechanism by which compound 3 exerted anti-neuroinflammatory effects was investigated by western blot and immunofluorescence assay, which suggested compound 3 inhibited LPS induced neuroinflammation via the suppression of toll-like receptor 4 (TLR4) dependent Signal Transducer and Activator of Transcription 3 (Stat3) and mitogen-activated protein kinase (MAPK) signaling pathways, and the activation of Heme Oxygenase-1 (HO-1) mediated signals.

Glucose-6-phosphate dehydrogenase: a therapeutic target for ovarian cancer.

INTRODUCTION: Ovarian cancer (OC) is a gynecological tumor disease, which is usually diagnosed at an advanced stage and has a poor prognosis. It has been established that the glucose metabolism rate of cancer cells is significantly higher than that of normal cells, and the pentose phosphate pathway (PPP) is an important branch pathway for glucose metabolism. Glucose-6-phosphate dehydrogenase (G6PD) is the key rate-limiting enzyme in the PPP, which plays an important role in the initiation and development of cancer (such as OC), and has been considered as a promisinganti-cancer target. AREAS COVERED: In this review, based on the structure and biological function of G6PD, recent research on the roles of G6PD in the progression, metastasis, and chemoresistance of OC are summarized and accompanied by proposed molecular mechanisms, which may provide a systematic understanding of targeting G6PD for the treatment of patients with OC. EXPERT OPINION: Accumulating evidence demonstrates that G6PD is a promising target of cancer. The development of G6PD inhibitors for cancer treatment merits broad application prospects.

MSKD: Structured knowledge distillation for efficient medical image segmentation.

In recent years, deep learning has revolutionized the field of medical image segmentation by enabling the development of powerful deep neural networks. However, these models tend to be complex and computationally demanding, posing challenges for practical implementation in clinical settings. To address this issue, we propose an efficient structured knowledge distillation framework that leverages a powerful teacher network to assist in training a lightweight student network. Specifically, we propose the Feature Filtering Distillation method, which focuses on transferring region-level semantic information while minimizing redundant information transmission from the teacher to the student network. This approach effectively mitigates the problem of inaccurate segmentation caused by similar internal organ characteristics. Additionally, we propose the Region Graph Distillation method, which exploits the higher-order representational capabilities of graphs to enable the student network to better imitate structured semantic information from the teacher. To validate the effectiveness of our proposed methods, we conducted experiments on the Synapse multi-organ segmentation and KiTS kidney tumor segmentation datasets using various network models. The results demonstrate that our method significantly improves the segmentation performance of lightweight neural networks, with improvements of up to 18.56% in Dice coefficient. Importantly, our approach achieves these improvements without introducing additional model parameters. Overall, our proposed knowledge distillation methods offer a promising solution for efficient medical image segmentation, empowering medical experts to make more accurate diagnoses and improve patient treatment.

Overexpression of 2-Cys Peroxiredoxin alleviates the NaHCO3 stress-induced photoinhibition and reactive oxygen species damage of tobacco.

Plant 2-cysteine peroxiredoxin (2-Cys Prx) is a mercaptan peroxidase localized in chloroplasts and has unique catalytic properties. To explore the salt stress tolerance mechanisms of 2-Cys Prx in plants, we analyzed the effects of overexpressing the 2-CysPrx gene on the physiological and biochemical metabolic processes of tobacco under NaHCO3 stress through joint physiological and transcriptomic analysis. These parameters included growth phenotype, chlorophyll, photosynthesis, and antioxidant system. After NaHCO3 stress treatment, a total of 5360 differentially expressed genes (DEGs) were identified in 2-Cysprx overexpressed (OE) plants, and the number of DEGs was significantly lower than 14558 in wild-type (WT) plants. KEGG enrichment analysis showed that DEGs were mainly enriched in photosynthetic pathways, photosynthetic antenna proteins, and porphyrin and chlorophyll metabolism. Overexpressing 2-CysPrx significantly reduced the growth inhibition of tobacco induced by NaHCO3 stress, alleviating the down-regulation of the DEGs related to chlorophyll synthesis, photosynthetic electron transport and the Calvin cycle and the up-regulation of those related to chlorophyll degradation. In addition, it also interacted with other redox systems such as thioredoxins (Trxs) and the NADPH-dependent Trx reductase C (NTRC), and mediated the positive regulation of the activities of antioxidant enzymes such as peroxidase (POD) and catalase (CAT) and the expression of related genes, thereby reducing the accumulation of superoxide anion (O2·-), hydrogen peroxide (H2O2) and malondialdehyde (MDA). In conclusion, 2-CysPrx overexpression could alleviate the NaHCO3 stress-induced photoinhibition and oxidative damage by regulating chlorophyll metabolism, promoting photosynthesis and participating in the regulation of antioxidant enzymes, and thus improve the ability of plants to resist salt stress damage.

Efficacy of PD-1 Inhibitors Combined with Anti-Angiogenic Therapy in Driver Gene Mutation Negative Non-Small-Cell Lung Cancer with Brain Metastases.

OBJECTIVE: Anti-angiogenic therapy has proven effective in non-small-cell lung cancer (NSCLC) patients. The purpose of this study was to evaluate the efficacy of programmed cell death protein 1 (PD-1) inhibitors combined with anti-angiogenic therapy in patients with driver gene mutation negative NSCLC and brain metastases (BMs). METHODS: A retrospective analysis was performed on NSCLC BMs in patients without driver gene mutations who received PD-1 inhibitors. Two groups, receiving either PD-1 inhibitor monotherapy or PD-1 inhibitor plus anti-angiogenesis therapy, were identified. The primary endpoints were overall survival (OS) and intracranial progression-free survival (iPFS). The secondary endpoints were safety, intracranial objective response rate (iORR) and intracranial disease control rate (iDCR). RESULTS: 113 NSCLC patients were included, 51 (45.1%) in the PD-1 inhibitor monotherapy group and 62 (54.9%) in the PD-1 inhibitor plus anti-angiogenesis therapy group. The median follow-up time was 26.2 months. OS was higher in the combination therapy cohort than in the monotherapy cohort (OS: 21.4 vs. 11.8 months; p = 0.004), with no significant difference in iPFS (p = 0.088). Moreover, the PD-1 inhibitor + anti-angiogenic therapeutic regimen exhibited the preferred iDCR (p = 0.005) but not the iORR (p = 0.121). There was no significant difference in the incidence of grade 3-4 adverse events between the two groups. In multivariate Cox regression analysis, PD-1 inhibitor therapy combined with anti-angiogenic treatment (p = 0.003) was an independent prognostic indicator of OS. CONCLUSIONS: Combining PD-1 inhibitor therapy with anti-angiogenic treatment significantly improves the OS of driver gene mutation negative NSCLC patients with BMs.

PRMT6 promotes tumorigenicity and cisplatin response of lung cancer through triggering 6PGD/ENO1 mediated cell metabolism.

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.

Pyrene-Based Self-Assembling Peptide for Ratiometric Detection of Heparin.

Heparin is a commonly used anticoagulant in clinical practice; however, excessive heparin can cause serious adverse reactions. Convenient and accurate detection of heparin levels is thus very important. In this research, a pyrene-based self-assembling fluorescent peptide PyFFRRR was designed for simple, selective, and efficient heparin detection. The guanidine groups in the arginine residues of PyFFRRR bind tightly with heparin, which is highly sulfated, through electrostatic interactions. Charge neutralization facilitated the self-assembly of PyFFRRR, resulting in its spectral response changing from deep blue monomer fluorescence to green excimer fluorescence. PyFFRRR exhibited excellent sensitivity and selectivity for ratiometric detection of heparin. The binding mechanism was investigated by using spectral and simulation tools, and structural observation. Finally, PyFFRRR was employed in human serum samples for ratiometric detection of heparin.

Trx CDSP32-overexpressing tobacco plants improves cadmium tolerance by modulating antioxidant mechanism.

The effects of overexpression of the thioredoxin-like protein CDSP32 (Trx CDSP32) on reactive oxygen species (ROS) metabolism in tobacco leaves exposed to cadmium (Cd) were studied by combining physiological measures and proteomics technology. Thus, the number of differentially expressed proteins (DEPs) in plants overexpressing the Trx CDSP32 gene in tobacco (OE) was observed to be evidently lower than that in wild-type (WT) tobacco under Cd exposure, especially the number of down-regulated DEPs. Cd exposure induced disordered ROS metabolism in tobacco leaves. Although Cd exposure inhibited the activities of superoxide dismutase (SOD), catalase (CAT), and l-ascorbate peroxidase (APX) and the expression of proteins related to the thioredoxin-peroxiredoxin (Trx-Prx) pathway, the increase in the activities of peroxidase (POD), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), glutathione reductase (GR), glutathione peroxidase (GPX), and glutathione S-transferase (GST) and their protein expression levels played an important role in the physiological response to Cd exposure. Notably, Trx CDSP32 was observed to alleviate the decrease in the expression and activities of SOD and CAT caused by Cd exposure and enhance the function of POD. Trx CDSP32 was observed to increase the H2O2 scavenging capacity of the ascorbic acid-glutathione (AsA-GSH) cycle and Trx-Prx pathway under Cd exposure, and it can especially regulate 2-Cys peroxiredoxin (2-Cys Prx) protein expression and thioredoxin peroxidase (TPX) activity. Thus, overexpression of the Trx CDSP32 gene can alleviate the oxidative damage that occurs in tobacco leaves under Cd exposure by modulating antioxidant defense systems.

Quassinoids from Picrasma chinensis with Insecticidal Activity against Adults and Larvae of Diaphorina citri Kuwayama and Neuroprotective Effect.

Eleven new tetracyclic quassinoids, picrachinensin A-K (1-11), along with six known congeners, were isolated from the stems and leaves of Picrasma chinensis. Their structures were elucidated by integrated multiple spectroscopic techniques, single-crystal X-ray diffraction analysis, and electronic circular dichroism. Notably, compounds 3 and 4 are a pair of undescribed epimers, and 8 and 9 are unusual quassinoids with a hydroxymethyl group at C-13. Biologically, compound 7 exhibited insecticidal activity on both adults and larvae of Diaphorina citri Kuwayama even more effectively than the positive control (abamectin), with an LD50 of 55.69 mg/L for adults and a corrected mortality rate of 30.42 ± 2.78% for larvae (100 mg/L). According to preliminary structure-activity relationship investigations, the hydroxymethyl at the C-13 position of quassinoids was beneficial for their insecticidal activity. In addition, compounds 1, 4, and 12 exhibited excellent neuroprotective effect against H2O2-induced oxidative injury on SH-SY5Y cells, with more potent activity than the positive control (Trolox), and all the compounds exhibited no cytotoxicity to SH-SY5Y and BV-2 cells at the indicated concentrations.

Stimuli-responsive platinum and ruthenium complexes for lung cancer therapy.

Lung cancer is the most common cause of cancer-related deaths worldwide. More efficient treatments are desperately needed. For decades, the success of platinum-based anticancer drugs has promoted the exploration of metal-based agents. Four ruthenium-based complexes have also entered clinical trials as candidates of anticancer metallodrugs. However, systemic toxicity, severe side effects and drug-resistance impeded their applications and efficacy. Stimuli-responsiveness of Pt- and Ru-based complexes provide a great chance to weaken the side effects and strengthen the clinical efficacy in drug design. This review provides an overview on the stimuli-responsive Pt- and Ru-based metallic anticancer drugs for lung cancer. They are categorized as endo-stimuli-responsive, exo-stimuli-responsive, and dual-stimuli-responsive prodrugs based on the nature of stimuli. We describe various representative examples of structure, response mechanism, and potential medical applications in lung cancer. In the end, we discuss the future opportunities and challenges in this field.

Constructing ECM-like Structure on the Plasma Membrane via Peptide Assembly to Regulate the Cellular Response.

This feature article introduces the design of self-assembling peptides that serve as the basic building blocks for the construction of extracellular matrix (ECM)-like structure in the vicinity of the plasma membrane. By covalently conjugating a bioactive motif, such as membrane protein binding ligand or enzymatic responsive building block, with a self-assembling motif, especially the aromatic peptide, a self-assembling peptide that retains bioactivity is obtained. Instructed by the target membrane protein or enzyme, the bioactive peptides self-assemble into ECM-like structure exerting various stimuli to regulate the cellular response via intracellular signaling, especially mechanotransduction. By briefly summarizing the properties and applications (e.g., wound healing, controlling cell motility and cell fate) of these peptides, we intend to illustrate the basic requirements and promises of the peptide assembly as a true bottom-up approach in the construction of artificial ECM.