Identification of piRNA Binding Sites Reveals the Argonaute Regulatory Landscape of the C. elegans Germline.

piRNAs (Piwi-interacting small RNAs) engage Piwi Argonautes to silence transposons and promote fertility in animal germlines. Genetic and computational studies have suggested that C. elegans piRNAs tolerate mismatched pairing and in principle could target every transcript. Here we employ in vivo cross-linking to identify transcriptome-wide interactions between piRNAs and target RNAs. We show that piRNAs engage all germline mRNAs and that piRNA binding follows microRNA-like pairing rules. Targeting correlates better with binding energy than with piRNA abundance, suggesting that piRNA concentration does not limit targeting. In mRNAs silenced by piRNAs, secondary small RNAs accumulate at the center and ends of piRNA binding sites. In germline-expressed mRNAs, however, targeting by the CSR-1 Argonaute correlates with reduced piRNA binding density and suppression of piRNA-associated secondary small RNAs. Our findings reveal physiologically important and nuanced regulation of individual piRNA targets and provide evidence for a comprehensive post-transcriptional regulatory step in germline gene expression.

Integrative splicing-quantitative-trait-locus analysis reveals risk loci for non-small-cell lung cancer.

Splicing quantitative trait loci (sQTLs) have been demonstrated to contribute to disease etiology by affecting alternative splicing. However, the role of sQTLs in the development of non-small-cell lung cancer (NSCLC) remains unknown. Thus, we performed a genome-wide sQTL study to identify genetic variants that affect alternative splicing in lung tissues from 116 individuals of Chinese ancestry, which resulted in the identification of 1,385 sQTL-harboring genes (sGenes) containing 378,210 significant variant-intron pairs. A comprehensive characterization of these sQTLs showed that they were enriched in actively transcribed regions, genetic regulatory elements, and splicing-factor-binding sites. Moreover, sQTLs were largely distinct from expression quantitative trait loci (eQTLs) and showed significant enrichment in potential risk loci of NSCLC. We also integrated sQTLs into NSCLC GWAS datasets (13,327 affected individuals and 13,328 control individuals) by using splice-transcriptome-wide association study (spTWAS) and identified alternative splicing events in 19 genes that were significantly associated with NSCLC risk. By using functional annotation and experiments, we confirmed an sQTL variant, rs35861926, that reduced the risk of lung adenocarcinoma (rs35861926-T, OR = 0.88, 95% confidence interval [CI]: 0.82-0.93, p = 1.87 × 10-5) by promoting FARP1 exon 20 skipping to downregulate the expression level of the long transcript FARP1-011. Transcript FARP1-011 promoted the migration and proliferation of lung adenocarcinoma cells. Overall, our study provided informative lung sQTL resources and insights into the molecular mechanisms linking sQTL variants to NSCLC risk.

Myeloid-derived suppressor cells from tumour-bearing mice induce the population expansion of CD19hiFcγRIIbhi regulatory B cells via PD-L1.

Myeloid-derived suppressor cells (MDSCs) increase in number and gain immunosuppressive functions in tumours and many other pathological conditions. MDSCs are characterized by their strong T-cell immunosuppressive capacity. The effects that MDSCs may have on B cells, especially within the tumour microenvironment, are less well understood. Here, we report that either monocytic MDSCs or polymorphonuclear MDSCs can promote increases in interleukin (IL)-10-expressing CD19hiFcγRIIbhi regulatory B cells in vitro and in vivo. Splenic transitional-1, -2, and -3 cells and marginal zone B cells, but not follicular B cells, differentiate into IL-10-expressing CD19hiFcγRIIbhi regulatory B cells. The adoptive transfer of CD19hiFcγRIIbhi regulatory B cells via tail vein injection can promote subcutaneous 3LL tumour growth in mice. The expression of programmed death-ligand 1 on MDSCs was found to be strongly associated with CD19hiFcγRIIbhi regulatory B cell population expansion. Furthermore, the frequency of circulating CD19+FcγRIIhi regulatory B cells was significantly increased in advanced-stage lung cancer patients. Our results unveil a critical role of MDSCs in regulatory B-cell differentiation and population expansion in lung cancer patients.

The Development of a CRISPR-FnCpf1 System for Large-Fragment Deletion and Multiplex Gene Editing in Acinetobacter baumannii.

Acinetobacter baumannii is a low-GC-content Gram-negative opportunistic pathogen that poses a serious global public health threat. Convenient and rapid genetic manipulation is beneficial for elucidating its pathogenic mechanisms and developing novel therapeutic methods. In this study, we report a new CRISPR-FnCpf1-based two-plasmid system for versatile and precise genome editing in A. baumannii. After identification, this new system prefers to recognize the 5'-TTN-3' (N = A, T, C or G) and the 5'-CTV-3' (V = A, C or G) protospacer-adjacent motif (PAM) sequence and utilize the spacer with lengths ranging from 19 to 25 nt. In direct comparison with the existing CRISPR-Cas9 system, it exhibits approximately four times the targetable range in A. baumannii. Moreover, by employing a tandem dual crRNA expression cassette, the new system can perform large-fragment deletion and simultaneous multiple gene editing, which is difficult to achieve via CRISPR-Cas9. Therefore, the new system is valuable and can greatly expand the genome editing toolbox of A. baumannii.

Integrative analyses of N6-methyladenosine-associated single-nucleotide polymorphisms (m6A-SNPs) identify tumor suppressor gene AK9 in lung cancer.

N6 -methyladenosine (m6 A) modification has been identified as one of the most important epigenetic regulation mechanisms in the development of human cancers. However, the association between m6 A-associated single-nucleotide polymorphisms (m6 A-SNPs) and lung cancer risk remains largely unknown. Here, we identified m6 A-SNPs and examined the association of these m6 A-SNPs with lung cancer risk in 13,793 lung cancer cases and 14,027 controls. In silico functional annotation was used to identify causal m6 A-SNPs and target genes. Furthermore, methylated RNA immunoprecipitation and quantitative real-time polymerase chain reaction (MeRIP-qPCR) assay was performed to assess the m6 A modification level of different genotypes of the causal SNP. In vitro assays were performed to validate the potential role of the target gene in lung cancer. A total of 8794 m6 A-SNPs were detected, among which 397 SNPs in nine susceptibility loci were associated with lung cancer risk, including six novel loci. Bioinformatics analyses indicated that rs1321328 in 6q21 was located around the m6 A modification site of AK9 and significantly reduced AK9 expression (ß = -0.15, p = 2.78 × 10-8 ). Moreover, AK9 was significantly downregulated in lung cancer tissues than that in adjacent normal tissues of samples from the Cancer Genome Atlas and Nanjing Lung Cancer Cohort. MeRIP-qPCR assay suggested that C allele of rs1321328 could significantly decrease the m6 A modification level of AK9 compared with G allele. In vitro assays verified the tumor-suppressing role of AK9 in lung cancer. These findings shed light on the pathogenic mechanism of lung cancer susceptibility loci linked with m6 A modification.

Integrated analysis of transcriptome and small RNAome reveals regulatory network of rapid and long-term response to heat stress in Rhododendron moulmainense.

MAIN CONCLUSION: The post-transcriptional gene regulatory pathway and small RNA pathway play important roles in regulating the rapid and long-term response of Rhododendron moulmainense to high-temperature stress. The Rhododendron plays an important role in maintaining ecological balance. However, it is difficult to domesticate for use in urban ecosystems due to their strict optimum growth temperature condition, and its evolution and adaptation are little known. Here, we combined transcriptome and small RNAome to reveal the rapid response and long-term adaptability regulation strategies in Rhododendron moulmainense under high-temperature stress. The post-transcriptional gene regulatory pathway plays important roles in stress response, in which the protein folding pathway is rapidly induced at 4 h after heat stress, and alternative splicing plays an important role in regulating gene expression at 7 days after heat stress. The chloroplasts oxidative damage is the main factor inhibiting photosynthesis efficiency. Through WGCNA analysis, we identified gene association patterns and potential key regulatory genes responsible for maintaining the ROS steady-state under heat stress. Finally, we found that the sRNA synthesis pathway is induced under heat stress. Combined with small RNAome, we found that more miRNAs are significantly changed under long-term heat stress. Furthermore, MYBs might play a central role in target gene interaction network of differentially expressed miRNAs in R. moulmainense under heat stress. MYBs are closely related to ABA, consistently, ABA synthesis and signaling pathways are significantly inhibited, and the change in stomatal aperture is not obvious under heat stress. Taken together, we gained valuable insights into the transplantation and long-term conservation domestication of Rhododendron, and provide genetic resources for genetic modification and molecular breeding to improve heat resistance in Rhododendron.

Cancer-associated fibroblast-secreted FGF7 as an ovarian cancer progression promoter.

BACKGROUND: Ovarian cancer (OC) is distinguished by its aggressive nature and the limited efficacy of current treatment strategies. Recent studies have emphasized the significant role of cancer-associated fibroblasts (CAFs) in OC development and progression. METHODS: Employing sophisticated machine learning techniques on bulk transcriptomic datasets, we identified fibroblast growth factor 7 (FGF7), derived from CAFs, as a potential oncogenic factor. We investigated the relationship between FGF7 expression and various clinical parameters. A series of in vitro experiments were undertaken to evaluate the effect of CAFs-derived FGF7 on OC cell activities, such as proliferation, migration, and invasion. Single-cell transcriptomic analysis was also conducted to elucidate the interaction between FGF7 and its receptor. Detailed mechanistic investigations sought to clarify the pathways through which FGF7 fosters OC progression. RESULTS: Our findings indicate that higher FGF7 levels correlate with advanced tumor stages, increased vascular invasion, and poorer prognosis. CAFs-derived FGF7 significantly enhanced OC cell proliferation, migration, and invasion. Single-cell analysis and in vitro studies revealed that CAFs-derived FGF7 inhibits the ubiquitination and degradation of hypoxia-inducible factor 1 alpha (HIF-1α) via FGFR2 interaction. Activation of the FGF7/HIF-1α pathway resulted in the upregulation of mesenchymal markers and downregulation of epithelial markers. Importantly, in vivo treatment with neutralizing antibodies targeting CAFs-derived FGF7 substantially reduced tumor growth. CONCLUSION: Neutralizing FGF7 in the medium or inhibiting HIF-1α signaling reversed the effects of FGF7-mediated EMT, emphasizing the dependence of FGF7-mediated EMT on HIF-1α activation. These findings suggest that targeting the FGF7/HIF-1α/EMT axis may offer new therapeutic opportunities to intervene in OC progression.

A near-infrared fluorescent probe with viscosity sensitivity in lysosome for cancer visualization.

A viscosity-sensitive, lysosome-targeted near-infrared fluorescent probe (PYATT) was reported in this paper. The fluorescent spectra of PYATT are strongly dependent on viscosity, resulting in a Stokes shift of about 190 nm. Given its photostability, low cytotoxicity, and high fluorescence quantum yield, PYATT is expected to be used in cell imaging. Due to the higher viscosity of tumor cells than normal cells, the fluorescence intensity of PYATT in tumor cells is higher than normal cells, which can realize the visualization of tumors. The near-infrared probe (PYATT) is viscosity-dependent in lysosomes, which is valuable in early diagnosis and treatment of tumor.

Effects of Kinesio taping on lower limb biomechanical characteristics during unexpected jumping in patients with chronic ankle instability.

PURPOSE: The current biomechanical research on the application of Kinesio taping (KT) to patients with chronic ankle instability (CAI) has focused on testing the expected movements. However, unexpected movements are more common in actual sports. Therefore, the present study aimed to investigate the effects of KT on the biomechanical characteristics of the knee and ankle joints during unexpected jumping movements. METHODS: Twenty-one patients with unilateral CAI were recruited to capture the biomechanical parameters during unexpected jumping movements under different interventions: no taping (NT), placebo taping (PT), and KT. A one-way repeated measures analysis of variance was used to compare the differences in knee and ankle biomechanical characteristics among patients with CAI between the three intervention conditions. RESULTS: At initial contact, the KT group demonstrated a significant decrease in ankle plantarflexion and knee flexion angles compared to the NT group (p < 0.05). At the early landing phase, the KT group had a significant increase in peak ankle dorsiflexion angle, peak ankle eversion angle, peak ankle dorsiflexion moment, and peak ankle eversion moment compared to the NT and PT groups (p < 0.05). Furthermore, the KT group had a significantly reduced peak knee flexion angle, peak knee eversion angle, and peak vertical ground reaction force (p < 0.05) compared to the NT and PT groups. CONCLUSION: KT significantly improves the sprain-prone touchdown posture of patients with CAI. And reducing the risk of ankle sprains during the early landing phase by promoting ankle dorsiflexion and eversion angles and moments.

Hierarchical cortical networks of "voice patches" for processing voices in human brain.

Humans have an extraordinary ability to recognize and differentiate voices. It is yet unclear whether voices are uniquely processed in the human brain. To explore the underlying neural mechanisms of voice processing, we recorded electrocorticographic signals from intracranial electrodes in epilepsy patients while they listened to six different categories of voice and nonvoice sounds. Subregions in the temporal lobe exhibited preferences for distinct voice stimuli, which were defined as "voice patches." Latency analyses suggested a dual hierarchical organization of the voice patches. We also found that voice patches were functionally connected under both task-engaged and resting states. Furthermore, the left motor areas were coactivated and correlated with the temporal voice patches during the sound-listening task. Taken together, this work reveals hierarchical cortical networks in the human brain for processing human voices.

End Group Nonplanarization Enhances Phototherapy Efficacy of A-D-A Fused-Ring Photosensitizer for Tumor Phototherapy.

Enhancing the phototherapy efficacy of organic photosensitizers through molecular design is a fascinating but challenging task. Herein, we propose a simple design strategy to first realize the generation of superoxide anion radical (O2•-) by A-D-A fused-ring photosensitizers. Through replacing one cyano group of traditional end group with an ester group, we designed a novel nonplanar end group (A unit) to synthesize a novel A-D-A photosensitizer F8CA. In a comparison with its counterpart F8CN with the traditional end group, F8CA displays more loose packing and larger spin-orbit coupling constants. The F8CA nanoparticles showed higher photodynamic activities with the generation capability of singlet oxygen (1O2), hydroxyl radical (•OH), and O2•-, while F8CN nanoparticles could only generate 1O2 and •OH. In addition, F8CA nanoparticles still remain high photothermal conversion efficiency (61%). As a result, F8CA nanoparticles perform well in hypoxia-tolerant tumor phototherapy. This study brings an effective design thought for A-D-A photosensitizers.

Phlorizin, an Important Glucoside: Research Progress on Its Biological Activity and Mechanism.

Phlorizin, as a flavonoid from a wide range of sources, is gradually becoming known for its biological activity. Phlorizin can exert antioxidant effects by regulating the IL-1ß/IKB-α/NF-KB signaling pathway. At the same time, it exerts its antibacterial activity by reducing intracellular DNA agglutination, reducing intracellular protein and energy synthesis, and destroying intracellular metabolism. In addition, phlorizin also has various pharmacological effects such as antiviral, antidiabetic, antitumor, and hepatoprotective effects. Based on domestic and foreign research reports, this article reviews the plant sources, extraction, and biological activities of phlorizin, providing a reference for improving the clinical application of phlorizin.

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OBJECTIVES: To investigate the risk factors for bronchopulmonary dysplasia (BPD) in twin preterm infants with a gestational age of <34 weeks, and to provide a basis for early identification of BPD in twin preterm infants in clinical practice. METHODS: A retrospective analysis was performed for the twin preterm infants with a gestational age of <34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020. According to their conditions, they were divided into group A (both twins had BPD), group B (only one twin had BPD), and group C (neither twin had BPD). The risk factors for BPD in twin preterm infants were analyzed. Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins. RESULTS: A total of 904 pairs of twins with a gestational age of <34 weeks were included in this study. The multivariate logistic regression analysis showed that compared with group C, birth weight discordance of >25% between the twins was an independent risk factor for BPD in one of the twins (OR=3.370, 95%CI: 1.500-7.568, P<0.05), and high gestational age at birth was a protective factor against BPD (P<0.05). The conditional logistic regression analysis of group B showed that small-for-gestational-age (SGA) birth was an independent risk factor for BPD in individual twins (OR=5.017, 95%CI: 1.040-24.190, P<0.05). CONCLUSIONS: The development of BPD in twin preterm infants is associated with gestational age, birth weight discordance between the twins, and SGA birth.

Transcriptomic Analysis of Mycobacterial Infected Macrophages Reveals a High MOI Specific Type I IFN Signaling.

Macrophage (MΦ) infection models are important tools for studying host-mycobacterial interactions. Although the multiplicity of infection (MOI) is an important experimental variable, the selection of MOI in mycobacterial infection experiments is largely empirical, without reference to solid experimental data. To provide relevant data, we used RNA-seq to analyze the gene expression profiles of MΦs 4 or 24 h after infection with Mycobacterium marinum (M. m) at MOIs ranging from 0.1 to 50. Analysis of differentially expressed genes (DEGs) showed that different MOIs are linked to distinct transcriptomic changes and only 10% of DEGs were shared by MΦ infected at all MOIs. KEGG pathway enrichment analysis revealed that type I interferon (IFN)-related pathways were inoculant dose-dependent and enriched only at high MOIs, whereas TNF pathways were inoculant dose-independent and enriched at all MOIs. Protein-protein interaction (PPI) network alignment showed that different MOIs had distinct key node genes. By fluorescence-activated cell sorting and follow-up RT-PCR analysis, we could separate infected MΦs from uninfected MΦs and found phagocytosis of mycobacteria to be the determinant factor for type I IFN production. The distinct transcriptional regulation of RAW264.7 MΦ genes at different MOIs was also seen with Mycobacterium tuberculosis (M.tb) infections and primary MΦ infection models. In summary, transcriptional profiling of mycobacterial infected MΦs revealed that different MOIs activate distinct immune pathways and the type I IFN pathway is activated only at high MOIs. This study should provide guidance for selecting the MOI most appropriate for different research questions.

A common whole-genome paleotetraploidization in Cucurbitales.

Cucurbitales are an important order of flowering plants known for encompassing edible plants of economic and medicinal value and numerous ornamental plants of horticultural value. By reanalyzing the genomes of two representative families (Cucurbitaceae and Begoniaceae) in Cucurbitales, we found that the previously identified Cucurbitaceae common paleotetraploidization that occurred shortly after the core-eudicot-common hexaploidization event is shared by Cucurbitales, including Begoniaceae. We built a multigenome alignment framework for Cucurbitales by identifying orthologs and paralogs and systematically redating key evolutionary events in Cucurbitales. Notably, characterizing the gene retention levels and genomic fractionation patterns between subgenomes generated from different polyploidizations in Cucurbitales suggested the autopolyploid nature of the Begoniaceae common tetraploidization and the allopolyploid nature of the Cucurbitales common tetraploidization and the Cucurbita-specific tetraploidization. Moreover, we constructed the ancestral Cucurbitales karyotype comprising 17 proto-chromosomes, confirming that the most recent common ancestor of Cucurbitaceae contained 15 proto-chromosomes and rejecting the previous hypothesis for an ancestral Cucurbitaceae karyotype with 12 proto-chromosomes. In addition, we found that the polyploidization and tandem duplication events promoted the expansion of gene families involved in the cucurbitacin biosynthesis pathway; however, gene loss and chromosomal rearrangements likely limited the expansion of these gene families.

Risk-benefit ratio of percutaneous kyphoplasty and percutaneous vertebroplasty in patients with newly diagnosed multiple myeloma with vertebral fracture: a single-center retrospective study.

The indications for percutaneous kyphoplasty (PKP) and percutaneous vertebroplasty (PVP) are painful vertebral compression fractures. Our study is to assess the risk-benefit ratio of PKP/PVP surgery in the patients with newly diagnosed multiple myeloma (NDMM) without receiving antimyeloma therapy. The clinical data of 426 consecutive patients with NDMM admitted to our center from February 2012 to April 2022 were retrospectively analyzed. The baseline data, postoperative pain relief, the proportion of recurrent vertebral fractures, and survival time were compared between the PKP/PVP surgical group and the nonsurgical group in the NDMM patients. Of the 426 patients with NDMM, 206 patients had vertebral fractures (206/426, 48.4%). Of these, 32 (32/206, 15.5%) underwent PKP/PVP surgery for misdiagnosis of simple osteoporosis prior to diagnosis of MM (surgical group), and the other 174 (174/206, 84.5%) did not undergo surgical treatment prior to definitive diagnosis of MM (non-surgical group). The median age of patients in the surgical and nonsurgical groups was 66 and 62 years, respectively (p = 0.01). The proportion of patients with advanced ISS and RISS stages was higher in the surgical group (ISS stage II + III 96.9% vs. 71.8%, p = 0.03; RISS stage III 96.9% vs. 71%, p = 0.01). Postoperatively, 10 patients (31.3%) never experienced pain relief and 20 patients (62.5%) experienced short-term pain relief with a median duration of relief of 2.6 months (0.2-24.1 months). Postoperative fractures of vertebrae other than the surgical site occurred in 24 patients (75%) in the surgical group, with a median time of 4.4 months postoperatively (0.4-86.8 months). Vertebral fractures other than the fracture site at the first visit occurred in 5 patients (2.9%) in the nonoperative group at the time of diagnosis of MM, with a median time of 11.9 months after the first visit (3.5-12.6 months). The incidence of secondary fractures was significantly higher in the surgical group than in the nonsurgical group (75% vs. 2.9%, p = 0.001). The time interval between the first visit and definitive diagnosis of MM was longer in the surgical group than in the nonsurgical group (6.1 months vs. 1.6 months, p = 0.01). At a median follow-up of 32 months (0.3-123 months), median overall survival (OS) was significantly shorter in the surgical group than in the nonsurgical group (48.2 months vs. 66 months, p = 0.04). Application of PKP/PVP surgery for pain relief in NDMM patients without antimyeloma therapy has a limited effect and a high risk of new vertebral fractures after surgery. Therefore, patients with NDMM may need to have their disease controlled with antimyeloma therapy prior to any consideration for PKP/PVP surgery.

Recycling Bonded Nd-Fe-B Magnet Wastes by Chemical Reaction and Its Mechanism.

The difficulty of short-process bonded Nd-Fe-B magnet waste recycling lies in the effective removal of the cured polymer matrix while protecting the magnetic powder. In this study, the polymer matrix in bonded Nd-Fe-B magnet waste was destroyed using sodium hydroxide ethanol solution, and the effect of the recycling process on the magnetic powders was studied. The nonmagnetic polymer matrix was removed, while the magnetic phase was not destroyed. The carbon and oxygen contents of the recycled magnetic powders decreased by 92.96 and 89.30%, respectively, while the MS (saturation magnetization), Mr (remanence), and Hcj (coercivity) values of the recycled magnetic powders were 99.8, 98.5, and 95.9% of the original magnetic powders, respectively. The curing and decomposition processes of the polymer matrix were also analyzed. During the curing process, dicyandiamide and bisphenol A epoxy resin acted as bridges and skeletons, respectively, finally forming a thermosetting three-dimensional network structure. In the alkaline alcohol solution, the bridges and skeletons were destroyed by the free hydroxyl groups and free hydrogen radicals in ethanol, and small molecular products were dissolved in the solution.

Emulsifying properties of plant-derived polypeptide and their conjugates: a self-consistent-field calculation study of the impact of hydrolysis.

By considering the hydrolysates of soy protein produced by trypsin as an example, the emulsion stabilizing properties of plant-based protein fragments have been investigated theoretically. We apply Self-Consistent-Field (SCF) calculations to determine the colloidal interactions induced between a pair of droplets stabilized by adsorbed layers of various soy protein fragments. The study is extended to conjugates of such polypeptides, formed by covalent bonding with a suitable hydrophilic sidechain (e.g. a polysaccharide). Our results show that the relatively longer fragments, with a greater number of hydrophobic amino acids, will display a stronger degree of adsorption affinity compared to the smaller hydrolysates, even where the latter may have a higher overall ratio of hydrophobic residues. This suggested that the degree of protein hydrolysis should be carefully controlled and limited to modest values to avoid the generation of a large number of short polypeptides, while still sufficient to improve solubility. While the emulsion stabilizing performance of a protein fragment type is strongly dependent on the conformation it adopts on the interface, we find this to be less critical for the conjugated polypeptides. However, we argue that with increasing degree of hydrolysis, many small fragments will not have the chance to form bonds with polysaccharides. It is demonstrated that the abundance of these unreacted polypeptides in the system severely reduces the efficiency of the conjugated longer protein fragments, preventing their presence on the surface of the droplets through competitive adsorption process.

Platinum(II)-Metallaclip-Based Theranostics for Cell Imaging and Synergetic Chemotherapy-Photodynamic Therapy.

Supramolecular coordination complexes formed by coordination-induced assembly not only avoid the loss of activity of precursors but also provide an efficient way for controlled release, which can be further used in various fields of biology such as drug delivery, cell imaging, and tumor treatment. In this work, a PtII metallaclip (4) was prepared from 4-[4-(1,2,2-triphenylvinyl)phenyl]pyridine (1), 5,10,15-triphenyl-20-(pyridin-4-yl)porphyrin (2), 90o Pt, and glycol-chain-modified isophthalic acid (3) in an acetone/water mixture through the "coordination-driven self-assembly" method. 31P and 1H NMR spectroscopy and high-resolution mass spectrometry were used to characterize the obtained metallaclip 4. 4 can self-assemble into fluorescent nanostructures in aqueous solution because of the tetraphenylethylene unit and its amphiphilic nature. Importantly, the fluorescent nanoparticles not only can be employed for cell imaging but also can generate singlet oxygen (1O2) under 660 nm laser irradiation and the release of Pt drug in the tumor issue for cancer therapy. The work may provide a new way for scientists to construct functional biomaterials with multiple applications via molecular self-assembly.

Emissive Nanoparticles from Co-assembly of Metallatetragon and Amphiphilic Tetraphenylethylene for Cancer Theranostics.

Platinum(II)-based metallacycles/cages have obtained tremendous attention due to their fascinating topology and wide range of applications, such as fluorescent materials, cell imaging, and tumor treatment. In this work, a metallatetragon (1) was constructed from 4-(4-(1,2,2-triphenylvinyl)phenyl)pyridine (2) and 90° cis-Pt(II) (Pt) in acetone through the strategy called "coordination driven self-assembly". Interestingly, through co-assembly of 1 and poly(ethylene glycol)-modified tetraphenylethylene (TPE-PEG22), fluorescent nanotheranostics, which could generate singlet oxygen (1O2) under the NIR irradiation and release Pt drugs under a low-pH microenvironment, were prepared successfully. The obtained theranostics could realize living cell imaging and synergistic chemo-photodynamic therapy in vitro and in vivo.