TMEM16F scramblase regulates angiogenesis via endothelial intracellular signaling.

TMEM16F, a Ca2+-activated lipid scramblase (CaPLSase) that dynamically disrupts lipid asymmetry, plays a crucial role in various physiological and pathological processes such as blood coagulation, neurodegeneration, cell-cell fusion, and viral infection. However, the mechanisms through which it regulates these processes remain largely elusive. Using endothelial cell-mediated angiogenesis as a model, here we report a previously unknown intracellular signaling function of TMEM16F. We demonstrate that TMEM16F deficiency impairs developmental retinal angiogenesis in mice and disrupts angiogenic processes in vitro. Biochemical analyses indicate that the absence of TMEM16F enhances the plasma membrane association of activated Src kinase. This in turn increases VE-cadherin phosphorylation and downregulation, accompanied by suppressed angiogenesis. Our findings not only highlight TMEM16F's intracellular signaling role in endothelial cells but also open new avenues for exploring the regulatory mechanisms of membrane lipid asymmetry and their implications in disease pathogenesis.

Molecular Evolution of Protein Sequences and Codon Usage in Monkeypox Viruses.

The monkeypox virus (mpox virus, MPXV) epidemic in 2022 has posed a significant public health risk. Yet, the evolutionary principles of MPXV remain largely unknown. Here, we examined the evolutionary patterns of protein sequences and codon usage in MPXV. We first demonstrated the signal of positive selection in OPG027, specifically in the Clade I lineage of MPXV. Subsequently, we discovered accelerated protein sequence evolution over time in the variants responsible for the 2022 outbreak. Furthermore, we showed strong epistasis between amino acid substitutions located in different genes. The codon adaptation index (CAI) analysis revealed that MPXV genes tended to use more non-preferred codons compared to human genes, and the CAI decreased over time and diverged between clades, with Clade I > IIa and IIb-A > IIb-B. While the decrease in fatality rate among the three groups aligned with the CAI pattern, it remains unclear whether this correlation was coincidental or if the deoptimization of codon usage in MPXV led to a reduction in fatality rates. This study sheds new light on the mechanisms that govern the evolution of MPXV in human populations.

Ti-Doped AgNbO3 as Novel Dense Diffusion Barriers of Limiting Current Oxygen Sensors.

The oxygen sensors with limiting current derived from a dense diffusion barrier have an excellent advantage of detecting oxygen partial pressure by controlling the ratio of air and fuel in combustion environments. Therefore, AgNb1-xTixO3-δ (wherein x varies from 0.1 to 0.3) was prepared as such a dense diffusion barrier layer for sensor application. Among the investigated compositions as a new condensed barrier for the diffusion of sensors, AgNb1-xTixO3-δ (x = 0.1, 0.2, 0.3) exhibits oxygen ionic conductivities from 1.37 × 10-4 to 5.78 × 10-3 S·cm-1 in the temperature range of 600-900 °C and outstanding stable electrochemical properties. Herein, we employ these novel materials as dense diffusion barriers and 8 mol % zirconia stabilized by yttria (8YSZ) as a solid-state electrolyte for the fabrication of the oxygen sensors with limiting current. We observed a direct connection between the limiting current and oxygen content within the interval of 0.5-5.0 mol % at 800 °C and a low working voltage. The increase of Ti-doping amount in AgNbO3 accelerates the sensing response to oxygen gas and promotes the service life of the sensor.

Rapid identification of full-length genome and tracing variations of monkeypox virus in clinical specimens based on mNGS and amplicon sequencing.

The monkeypox virus (MPXV) has triggered a current outbreak globally. Genome sequencing of MPXV and rapid tracing of genetic variants will benefit disease diagnosis and control. It is a significant challenge but necessary to optimize the strategy and application of rapid full-length genome identification and to track variations of MPXV in clinical specimens with low viral loads, as it is one of the DNA viruses with the largest genome and the most AT-biased, and has a significant number of tandem repeats. Here we evaluated the performance of metagenomic and amplicon sequencing techniques, and three sequencing platforms in MPXV genome sequencing based on multiple clinical specimens of five mpox cases in Chinese mainland. We rapidly identified the full-length genome of MPXV with the assembly of accurate tandem repeats in multiple clinical specimens. Amplicon sequencing enables cost-effective and rapid sequencing of clinical specimens to obtain high-quality MPXV genomes. Third-generation sequencing facilitates the assembly of the terminal tandem repeat regions in the monkeypox virus genome and corrects a common misassembly in published sequences. Besides, several intra-host single nucleotide variations were identified in the first imported mpox case. This study offers an evaluation of various strategies aimed at identifying the complete genome of MPXV in clinical specimens. The findings of this study will significantly enhance the surveillance of MPXV.

Endothelial TMEM16F lipid scramblase regulates angiogenesis.

Dynamic loss of lipid asymmetry through the activation of TMEM16 Ca2+-activated lipid scramblases (CaPLSases) has been increasingly recognized as an essential membrane event in a wide range of physiological and pathological processes, including blood coagulation, microparticle release, bone development, pain sensation, cell-cell fusion, and viral infection. Despite the recent implications of TMEM16F CaPLSase in vascular development and endothelial cell-mediated coagulation, its signaling role in endothelial biology remains to be established. Here, we show that endothelial TMEM16F regulates in vitro and in vivo angiogenesis through intracellular signaling. Developmental retinal angiogenesis is significantly impaired in TMEM16F deficient mice, as evidenced by fewer vascular loops and larger loop areas. Consistent with our in vivo observation, TMEM16F siRNA knockdown in human umbilical vein endothelial cells compromises angiogenesis in vitro. We further discovered that TMEM16F knockdown enhances VE-cadherin phosphorylation and reduces its expression. Moreover, TMEM16F knockdown also promotes Src kinase phosphorylation at tyrosine 416, which may be responsible for downregulating VE-cadherin expression. Our study thus uncovers a new biological function of TMEM16F in angiogenesis and provides a potential mechanism for how the CaPLSase regulates angiogenesis through intracellular signaling.

[Change in Granulation Potential and Microbial Enrichment Characteristics of Sludge Induced by Microplastics].

Microplastics (MPs), as a new type of pollutant, are widely detected in sewage treatment plants. Currently, research on MPs in traditional sewage treatment systems has mainly been focused on the pollution level and distribution characteristics, with a lack of studying the impact of MPs on the sludge granulation. In order to explore the effect of MPs on the granulation process, a microplastic exposure test was conducted by adding polyethylene terephthalate microplastics (PET-MPs), which are widespread in the environment. The operating performance of the system, extracellular polymeric substance (EPS) composition, and flora enrichment were analyzed on the sludge granulation. The results showed that the exposure of PET-MPs significantly accelerated the sludge granulation process, whereas the increase in EPS content dominated by PN enhanced the sludge surface hydrophobicity; the granulation rate and EPS secretion were proportional to the exposed particle size. Microplastics and EPS secretions synergistically promoted the formation of granular sludge. However, continuous microplastic exposure led to deterioration of the system decontamination performance and inhibited the degradation process of pollutants, with the most negative effect of nitrite nitrogen accumulation under 250 µm PET-MPs exposure, as high as (5.08±0.24) mg·L-1. The high-throughput sequencing revealed that the microbial community diversity fell in the experimental group. The dominant bacteria at the phylum level were Proteobacteria and Bacteroidota on the sludge granulation. Rhodocyclaceae, Sphingomonadaceae, Flavobacteriaceae, and Rhodanobacteraceae promoted flocculation by increasing EPS secretion. The decrease in Comamonadaceae and Chitinophagaceae weakened the ammonia and nitrite oxidation capacity of the system, whereas the decrease in Rhodobacteraceae, Hyphomonadaceae, and Xanthomonadaceae inhibited the removal of nitrate nitrogen.

Optimization and Deoptimization of Codons in SARS-CoV-2 and Related Implications for Vaccine Development.

The spread of coronavirus disease 2019 (COVID-19), caused by severe respiratory syndrome coronavirus 2 (SARS-CoV-2), has progressed into a global pandemic. To date, thousands of genetic variants have been identified among SARS-CoV-2 isolates collected from patients. Sequence analysis reveals that the codon adaptation index (CAI) values of viral sequences have decreased over time but with occasional fluctuations. Through evolution modeling, it is found that this phenomenon may result from the virus's mutation preference during transmission. Using dual-luciferase assays, it is further discovered that the deoptimization of codons in the viral sequence may weaken protein expression during virus evolution, indicating that codon usage may play an important role in virus fitness. Finally, given the importance of codon usage in protein expression and particularly for mRNA vaccines, it is designed several codon-optimized Omicron BA.2.12.1, BA.4/5, and XBB.1.5 spike mRNA vaccine candidates and experimentally validated their high levels of expression. This study highlights the importance of codon usage in virus evolution and provides guidelines for codon optimization in mRNA and DNA vaccine development.

Mitochondrial energy metabolism is downregulated in repeated implantation failure patients related to alteration of PGC-1α acetylation level.

Herein we aimed at exploring mitochondrial energy metabolism status in patients with repeated implantation failure (RIF) and whether key regulatory factor PGC-1α of energy metabolism is involved in the decidualization of endometrial stromal cells. Mitochondrial oxidative phosphorylation level and ATP synthesis were compared in primary endometrial stromal cells from RIF and control group. At the same time, as one of key transcription regulators of mitochondrial energy metabolism, the expression level and acetylation level of PGC-1α were compared with two groups. Then, we downregulated the acetylation levels of PGC-1α, and the expression of decidual markers (PRL and IGFBP1) was observed further. Mitochondrial energy metabolism, showing by mitochondrial oxidative phosphorylation level and ATP synthesis, was decreased in the endometrial stromal cells of the RIF group (RIF-hEnSCs). Meanwhile, PGC-1α acetylation levels were significantly higher in RIF-hEnSCs. When we reduced the acetylation levels of PGC-1α in RIF-hEnSCs, the basal O2 consumption rate and maximal respiration were increased, and also the PRL and IGFBP1. Overall, our data indicated that the endometrial stromal cells of the RIF patients had low level of mitochondrial energy metabolism. Reducing acetylation level of key energy metabolism regulator PGC-1α can increase the decidualization level of RIF-hEnSCs. These findings may inspire new ideas about the treatment of RIF.

Conductivity and aging behavior of Sr(Ti0.6Fe0.4)1-x O3-δ mixed conductor materials.

Perovskite materials play a significant role in oxygen sensors due to their fascinating electrical and ionic conductivities. The sol-gel technique was employed to prepare various compositions of B-site-deficient Fe-doped SrTiO3 (iron-doped strontium titanate) or Sr(Ti0.6Fe0.4)1-x O3-δ , where x = 0.01, 0.02, and 0.03. The XRD results revealed that the principle crystalline phase of the samples was the cubic perovskite structure. The B-site deficiency improved the ionic and total conductivities of Sr(Ti0.6Fe0.4)1-x O3-δ . A small polaron conduction behavior occurred in the total electrical conductivity. The XPS results showed that the oxygen vacancy value decreased with the rise in the amount of B-site deficiencies. A lower B-site deficiency amount could produce more oxygen vacancies in the lattice but resulted in the ordering of vacancies and then lower ionic conductivity. The aging behavior was caused by the ordering of oxygen vacancies and resulted in a degeneration of electrical features under a long service time. Conversely, augmentation of the B-site deficiency amount inhibited the tendency for the ordering of oxygen vacancies and then promoted the electrical performance under a long usage time. The conduction mechanism of oxygen ions through oxygen vacancies was thoroughly investigated and discussed. The current study presents a feasible approach to ameliorate the physical features of conductors through doping the B-site of the perovskite layer with Fe, which would be a fruitful approach for numerous applications, including oxygen sensors and fuel cells anodes.

The Adsorption of CTC onto CFBs: A Study on Fabrication of Magnetic Cellulose/Fe3O4 Beads (CFBs) and Adsorption Kinetics.

Magnetic cellulose/Fe3O4 beads (CFBs) were fabricated by dispersing Fe3O4 particles in a microcrystalline cellulose (MCC) matrix. The CFBs were characterized by X-ray diffraction (XRD), vibrating sample magnetometry (VSM), energy dispersive X-ray spectrometry (EDS), Brunauer-Emmett-Teller (BET) analysis and scanning electron microscopy (SEM). The adsorption behaviors of CFBs were studied by chlortetracycline hydrochloride (CTC) adsorption experiments. By means of adsorption kinetics and isotherms, the adsorption mechanisms were explored. The results show that quasi-spherical CFBs with a BET surface area as high as 119.63 m2/g were successfully tailored, with the high saturation magnetization (Ms > 40 emu/g) guaranteeing the magnetic separation of CFBs from wastewater. The process of adsorbing CTC onto CFBs involves monolayer chemical adsorption, and the maximum adsorption capacity for CTC estimated by the Langmuir model is 89.53 mg/g. The CFB product shows better adsorption performance in acidic solution than in basic solution.

Classification of main pancreatic duct and treatment strategy after linear stapler closure of pancreatic neck in laparoscopic pancreaticoduodenectomy / 国际外科学杂志

Objective:To investigate the classification of main pancreatic duct and treatment strategy after linear stapler closure of pancreatic neck in laparoscopic pancreaticoduodenectomy (LPD).Methods:The records of 51 consecutive patients with LPD who were treated by linear staple closure technique of pancreatic neck from February to December 2022 from Binzhou Second People′s Hospital, Shijingshan Campus, Beijing Chaoyang Hospital, Capital Medical University, Rizhao Hepatobiliary-Pancreatic-Splenic Surgery Research Institute, Chaoyang Central Hospital, Shandong Juxian People′s Hospital, Weihai Municipal Hospital, Binzhou Central Hospital, and Affiliated Hospital of Chifeng University were retrospectively reviewed. According to the visibility, position and diameter of the main pancreatic duct at the stump of the pancreas, the type of main pancreatic duct was divided into type I, type Ⅱ, type Ⅲa and type Ⅲb. The number of cases in each main pancreatic duct classification and the corresponding treatment strategies were examined.Results:A total of 51 cases of LPD were successfully completed. Of these patients, the males comprised 56.9%(29/51), and females comprised 43.1%(22/51), with age ranging from 31 to 88 years old. The type of the main pancreatic duct at the stump of the pancreas included 7 cases (13.7%) of type Ⅰ, 39 cases (76.5%) of type Ⅱ, 2 cases (3.9%) of type Ⅲa, and 3 cases (5.9%) of type Ⅲb. Corresponding treatment strategies were adopted according to different main pancreatic duct types, the main pancreatic duct was successfully found, and a support drainage tube was inserted.Conclusion:After linear stapler closure of pancreatic neck, corresponding treatment strategies should be adopted according to the classification of the main pancreatic duct, which would help to improve the success rate of finding the main pancreatic duct and placing a support drainage tube.

Surface-enhanced Raman scattering as a potential strategy for wearable flexible sensing and point-of-care testing non-invasive medical diagnosis.

As a powerful and effective analytical tool, surface-enhanced Raman scattering (SERS) has attracted considerable research interest in the fields of wearable flexible sensing and non-invasive point-of-care testing (POCT) medical diagnosis. In this mini-review, we briefly summarize the design strategy, the development progress of wearable SERS sensors and its applications in this field. We present SERS substrate analysis of material design requirements for wearable sensors and highlight the benefits of novel plasmonic particle-in-cavity (PIC)-based nanostructures for flexible SERS sensors, as well as the unique interfacial adhesion effect and excellent mechanical properties of natural silk fibroin (SF) derived from natural cocoons, indicating promising futures for applications in the field of flexible electronic, optical, and electrical sensors. Additionally, SERS wearable sensors have shown great potential in the fields of different disease markers as well as in the diagnosis testing for COVID-19. Finally, the current challenges in this field are pointed out, as well as the promising prospects of combining SERS wearable sensors with other portable health monitoring systems for POCT medical diagnosis in the future.

Inhibitory effects of pH, salinity, and tea polyphenols concentration on the specific spoilage organisms isolated from lightly-salted large yellow croaker (Pseudosciaena crocea).

Proteus vulgaris and Hafnia alvei were identified as specific spoilage organisms (SSOs) isolated from the refrigerated lightly-salted large yellow croaker (Pseudosciaena crocea). In this work, the inhibitory effects of pH, salinity, and tea polyphenols concentration on both strains were investigated. Modified Gompertz models were used to estimate the kinetic parameters µm (maximum specific growth rate) and λ (duration of lag phase) of the two strains under different conditions, demonstrating that their growth rates decreased with the decrease of pH as well as the increase of salinity and tea polyphenols concentration, and the growths of both strains stopped while the salinity and tea polyphenols concentration increased to 0.05 and 5%, respectively. Response surface methodology (RSM) based on a three-level three-factor Box-Behnken Design (BBD) was employed to optimize the combination of these three antibacterial factors. The results showed that the optimum inhibitory conditions were: tea polyphenols concentration 0.05%, salinity 3.46%, and pH 6.96 to inhibit the growth of P. vulgaris; tea polyphenols concentration 0.05%, salinity 3.45%, and pH 6.94 to inhibit H. alvei. Validation experiments were performed and demonstrated that under these conditions, the growth of the two SSOs could be 100% inhibited. This research provided references for the inhibition of the SSOs of lightly-salted large yellow croaker and the extension of its shelf life.

A supramolecular self-assembled nanomaterial for synergistic therapy of immunosuppressive tumor.

Triple negative breast cancer (TNBC) is an immunosuppressive "cold" tumor that lacks immune cell infiltration and activation, resulting in a poor response to immune checkpoint blockade (ICB) therapies. In addition, TNBC is poorly responsive to targeted therapies due to the absence of efficient molecular targets. A strategy that can block molecular signal transduction, stimulate immunogenicity, and activate the immune response is a promising approach to achieve ideal clinical benefit. Herein, we designed and synthesized an aggregation-induced emission luminogen (AIEgen)-conjugated self-assembling peptide that targets epidermal growth factor receptor (EGFR), named TPA-FFG-LA. TPA-FFG-LA peptides form nanoassemblies on the surface of EGFR-positive TNBC cells and are internalized into cells through endocytosis, which inhibit EGFR signaling transduction and provoke lysosomal membrane permeabilization (LMP). Upon light irradiation, the aggregated AIEgens produce massive reactive oxygen species (ROS) to exacerbate LMP and trigger immunogenic cell death (ICD), resulting in elimination of residual EGFR-negative tumor cells and exerting long-term antitumor effects. The in vitro and in vivo experiments verified that TPA-FFG-LA nanoassemblies suppress tumor growth, provoke immune cell activation and infiltration, and cause EGFR degradation and LMP. These results suggest that the combination of supramolecular assembly induced molecular targeting effects and lysosome dysfunction with ICD-stimulated immune activation is a plausible strategy for the efficient therapy of immunosuppressive TNBC.

Highly bright aggregation-induced emission nanodots for precise photoacoustic/NIR-II fluorescence imaging-guided resection of neuroendocrine neoplasms and sentinel lymph nodes.

Owing to the complementary high spatial resolution and signal-to-noise ratio, the dual-modality imaging technique of photoacoustic imaging (PAI)/the second near-infrared window fluorescence imaging (NIR-II FI) holds great promise for the detection of tumor tissues and sentinel lymph nodes (SLNs). Herein, by developing two aggregation-induced emission luminogens (AIEgens) (C-NTBD and O-NTBD) with benzodithiadiazole as the electron acceptor, PAI/NIR-II FI was applied to the diagnosis and treatment of neuroendocrine neoplasms (NENs) and their SLNs for the first time. Both AIEgens exhibited good PAI properties as well as intense NIR-II fluorescence emission. Among them, C-NTBD nanoparticles (NPs) have better PAI and NIR-II FI performance with maximum absorption at 732 nm and emission peak at 1042 nm. In NENs-bearing nude mice model, after successful preoperative localization of NENs by PAI, NIR-II FI was then used to detect SLNs. Under the NIR-II FI guidance of C-NTBD NPs, an SLN with a diameter of 1 mm located in the chest wall and far away from the primary tumor site was even detected and precisely removed. This dual-modality imaging technology could improve the detection of NENs and the accuracy of intraoperative SLNs dissection, improve patient prognosis, and provide a new strategy for the precise treatment of NENs.

An Activatable Near-Infrared Afterglow Theranostic Prodrug with Self-Sustainable Magnification Effect of Immunogenic Cell Death.

Herein, we report an activatable near-infrared (NIR) afterglow theranostic prodrug that circumvents high background noise interference caused by external light excitation. The prodrug can release hydroxycamptothecin (HCPT) in response to the high intratumoral peroxynitrite level associated with immunogenic cell death (ICD), and synchronously activate afterglow signal to monitor the drug release process and cold-to-hot tumor transformation. The prodrug itself is an ICD inducer achieved by photodynamic therapy (PDT). PDT initiates ICD and recruits first-arrived neutrophils to secrete peroxynitrite to trigger HCPT release. Intriguingly, we demonstrate that HCPT can significantly amplify PDT-mediated ICD process. The prodrug thus shows a self-sustainable ICD magnification effect by establishing an "ICD-HCPT release-amplified ICD" cycling loop. In vivo studies demonstrate that the prodrug can eradicate existing tumors and prevent further tumor recurrence through antitumor immune response.

Knowledge, Attitudes, and Practices toward COVID-19 and Vaccines among Chinese Small-Town Residents: A Cross-sectional Study.

China has basically controlled the COVID-19 epidemic as a result of widespread vaccination and other containment strategies, despite localized outbreaks, as of September 2021. This study investigates the knowledge, attitudes, and practices (KAP) of COVID-19 and COVID-19 vaccines among Chinese small-town residents to provide suggestions for public health policy. Residents who were vaccinated against COVID-19 were asked to complete a paper questionnaire on KAP in Xidian, Zhejiang. The knowledge questionnaire consisted of 12 questions regarding COVID-19 and 12 questions regarding COVID-19 vaccines. Attitude and practice evaluation included agreement on the eventual control of COVID-19 and having recently worn a mask outside. Of 405 survey responders, 52.3% were male, 71.4% had middle school education or less, and 59.0% engaged in physical labor as an occupation. The correct answer rates of the COVID-19 section and the vaccine section were 79.2% and 71.7%, respectively. Age groups of 18 to 29 years and > 50 years, occupations of physical labor and unemployment, and primary school education and less were associated with lower knowledge scores. The majority of participants (91.6%) believed that COVID-19 will eventually be controlled, whereas women, students, and patients with chronic held relatively negative attitudes toward epidemic control. Most participants (87.4%) wore masks outside recently. In conclusion, Chinese small-town residents have a medium level of knowledge regarding COVID-19 and vaccines, hold positive attitudes, and have appropriate practices. Health education should be provided to the target populations to enrich their knowledge of COVID-19 and vaccines, and to improve their attitudes toward epidemic control.

Functional coupling between TRPV4 channel and TMEM16F modulates human trophoblast fusion.

TMEM16F, a Ca2+-activated phospholipid scramblase (CaPLSase), is critical for placental trophoblast syncytialization, HIV infection, and SARS-CoV2-mediated syncytialization, however, how TMEM16F is activated during cell fusion is unclear. Here, using trophoblasts as a model for cell fusion, we demonstrate that Ca2+ influx through the Ca2+ permeable transient receptor potential vanilloid channel TRPV4 is critical for TMEM16F activation and plays a role in subsequent human trophoblast fusion. GSK1016790A, a TRPV4 specific agonist, robustly activates TMEM16F in trophoblasts. We also show that TRPV4 and TMEM16F are functionally coupled within Ca2+ microdomains in a human trophoblast cell line using patch-clamp electrophysiology. Pharmacological inhibition or gene silencing of TRPV4 hinders TMEM16F activation and subsequent trophoblast syncytialization. Our study uncovers the functional expression of TRPV4 and one of the physiological activation mechanisms of TMEM16F in human trophoblasts, thus providing us with novel strategies to regulate CaPLSase activity as a critical checkpoint of physiologically and disease-relevant cell fusion events.

Semiconducting Polymer Nanoparticles with Surface-Mimicking Protein Secondary Structure as Lysosome-Targeting Chimaeras for Self-Synergistic Cancer Immunotherapy.

Immunotherapy has received tremendous attention for tumor treatment, but the efficacy is greatly hindered by insufficient tumor-infiltration of immune cells and immunosuppressive tumor microenvironment. The strategy that can efficiently activate cytotoxic T lymphocytes and inhibit negative immune regulators will greatly amplify immunotherapy outcome, which is however very rare. Herein, a new kind of semiconducting polymer (SP) nanoparticles is developed, featured with surface-mimicking protein secondary structure (SPSS NPs) for self-synergistic cancer immunotherapy by combining immunogenic cell death (ICD) and immune checkpoint blockade therapy. The SPs with excellent photodynamic property are synthesized by rational fluorination, which can massively induce ICD. Additionally, the peptide antagonists are introduced and self-assembled into ß-sheet protein secondary structures on the photodynamic NP surface via preparation process optimization, which function as efficient lysosome-targeting chimaeras (LYTACs) to mediate the degradation of programmed cell death ligand-1 (PD-L1) in lysosome. In vivo experiments demonstrate that SPSS NPs can not only elicit strong antitumor immunity to suppress both primary tumor and distant tumor, but also evoke long-term immunological memory against tumor rechallenge. This work introduces a new kind of robust immunotherapy agents by combining well-designed photosensitizer-based ICD induction and protein secondary structures-mediated LYTAC-like multivalence PD-L1 blockade, rendering great promise for synergistic immunotherapy.

LncRNA cancer susceptibility 20 regulates the metastasis of human gastric cancer cells via the miR-143-5p/MEMO1 molecular axis.

BACKGROUND: Gastric cancer (GC) is considered as one of the most widespread malignancies. Emerging evidence has shown that lncRNAs can function as important oncogenes or tumor suppressors during GC progression. AIM: To investigate the effect and mechanism of lncRNA cancer susceptibility 20 (CASC20) in the proliferation and metastasis of GC cells. METHODS: Data mining and clinical samples were used to evaluate the expression of CASC20 in GC and adjacent tissues. CASC20 was down-regulated in GC cells by short-interfering RNA. Cell proliferation was evaluated by CCK-8 assay, and cell migration and invasion were detected by wound healing and Transwell assays. The expressions of proteins related to epithelial-mesenchymal transition were detected by western blot assay. RESULTS: The expression of CASC20 was increased in GC tumor tissues and various GC cell lines. High CASC20 expression was correlated with a high risk of lymphatic metastasis and poor prognosis in GC patients. In vitro assays showed that silencing CASC20 reduced cell proliferation, migration, and invasion in GC cells. Mechanistic studies revealed that CASC20 exhibits oncogenic functions by regulating MEMO1 expression through competitive endogenous binding to miR-143-5p, leading to induction of epithelial-mesenchymal transition. CONCLUSION: Our findings indicate that CASC20 serves as a tumor promoter by regulating metastasis in GC via the miR-143-5p/MEMO1 axis. CASC20 may be a potential therapeutic target for GC.