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Background Lung adenocarcinoma (LUAD) is the most prevalent form of lung cancer, with high mortality and poor prognosis. Anoikis, a type of programmed cell apoptosis, plays a vital role in the progression of tumors. Herein, we established a signature based on anoikis-related lncRNAs to predict the prognosis of LUAD patients. Method Genomic and clinical data were downloaded from the TCGA database. Coexpression analysis and Cox regression were conducted to establish the prognostic signature. Kaplan–Meier curves and ROC curves were used to validate the accuracy of the model, and a nomogram based on the signature was constructed. Subsequently, gene set enrichment analysis, immune analysis and drug sensitivity analysis were performed. Result Nine anoikis-related lncRNAs (AC090912.1, LINC00707, AC026355.2, FOCAD-AS1, LINC00460, LINC01117, AC068228.1, AP000346.1 and LINC01537) were obtained to develop a prognostic signature. The K-M curves showed that the high-risk group was correlated with worse overall survival, progression-free survival and disease-specific survival. The area under the ROC curves for 1-, 3-, and 5-year overall survival (0.722, 0.704 and 0.709, respectively) and the C-index demonstrated that the signature has higher predictive value than clinical factors. Functional enrichment analysis showed that lncRANs participated in tumor progression. Patients in the low-risk group had a better prognosis, more immune cell infiltration, and higher immune scores. We also observed different sensitivities to anticancer drugs in the two groups, which can guide treatment. Conclusion We developed and estimated a novel anoikis-related lncRNA signature that may be used to predict the prognosis of LUAD patients.

Zijuan Meng,1 Zhaojun Chen,1 Guangwen Lu,1 Xiaoqi Dong,1 Jun Dai,2 Xiaoding Lou,1 Fan Xia1 1Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan, 430074, People’s Republic of China; 2Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430034, People’s Republic of ChinaCorrespondence: Jun Dai, Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430034, People’s Republic of China, Email dj_hust1987@sina.com; jundai@tjh.tjmu.edu.cnBackground: White-light photodynamic therapy (wPDT) has been used in the treatment of cancer due to its convenience, effectiveness and less painful. However, the limited penetration of white-light into the tissues leads to a reduced effectiveness of solid tumor treatment.Methods: Two short-wavelength aggregation-induced emission (AIE) nanoparticles were prepared, PyTPA@PEG and TB@PEG, which have excitation wavelengths of 440 nm and 524 nm, respectively. They were characterized by UV, fluorescence, particle size and TEM. The ability of nanoparticles to produce reactive oxygen species (ROS) and kill cancer cells under different conditions was investigated in vitro, including white-light, after white-light penetrating the skin, laser. A white-light fiber for intra-tumor irradiation was customized. Finally, induced tumor elimination with fiber-mediated wPDT was confirmed in vivo.Results: In vitro, both PyTPA@PEG and TB@PEG are more efficient in the production ROS when exposed to white-light compared to laser. However, wPDT also has a fatal flaw in that its level of ROS production after penetrating the skin is reduced to 20– 40% of the original level. To this end, we have customized a white-light fiber for intra-tumor irradiation. In vivo, the fiber-mediated wPDT significantly induces tumor elimination with maximized therapeutic outcomes by irradiating the interior of the tumor. In addition, wPDT also has the advantage that its light source can be adapted to a wide range of photosensitizers (wavelength range 400– 700 nm), whereas a laser of single wavelength can only target a specific photosensitizer.Conclusion: This method of using optical fiber to increase the tissue penetration of white light can greatly improve the therapeutic effect of AIE photosensitizers, which is needed for the treatment of large/deep tumors and holds great promise in cancer treatment.Keywords: aggregation-induced emission, photodynamic therapy, photosensitizer, white light, fiber optic

Chemotherapy is a widely used and effective adjuvant treatment for cancer, and it has unavoidable damage to female fertility, with statistics showing 38% of women who have received chemotherapy are infertile. How to reduce fertility toxicity while enhancing the oncologic chemotherapy is a clinical challenge. Herein, we developed the co-delivery micelles (BML@PMP), which are composed of a reduction-sensitive paclitaxel prodrug (PMP) for chemotherapy and a CHEK2 inhibitor (BML277) for both fertility protection and chemotherapy enhancement. BML@PMP achieves fertility protection through three actions. (1) Due to the enhanced permeability and retention (EPR) effect, BML@PMP is more enriched in the tumor, while very little in the ovary (about 1/10th of the tumor). (2) Glutathione (GSH) triggers the release of PTX, and with low levels of GSH in the ovary, the amount of PTX released in the ovary is correspondingly reduced. (3) BML277 inhibits oocyte apoptosis by inhibiting the CHEK2-TAp63α pathway. Because of the different downstream targets of CHEK2 in tumor cells and oocytes, BML277 also enhances chemotherapeutic efficacy by reducing DNA damage repair which is activated through the CHEK2 pathway. This bidirectional effect of CHEK2 inhibitor-based co-delivery system represents a promising strategy for improving oncology treatment indices and preventing chemotherapy-associated fertility damage. This article is protected by copyright. All rights reserved.

Precisely analyzing the target materials in living cells can reveal the essence and mystery of life at a deeper level, which will provide reliable theoretical basis for the occurrence, development, treatment and prognosis of major diseases. However, because living cells are in the dynamic process of metabolism, there are several challenges existed in accurate analysis, including subcellular compartment heterogeneity, plasma membrane interface barrier, and cell cycle regulation. In this regard, our group has designed and synthesized a series of multifunctional aggregates by mainly integrating the peptide elements, nucleic acid elements and aggregation elements to overcome the barriers. This article summarizes the latest developments of multifunctional aggregates for precise cell analysis by our group, and systematically introduces them according to different design concepts and targeting dimensions, such as space, efficiency as well as time. We hope this work could contribute to analyzing the biomarkers in cells through constructing the multifunctional aggregates, understanding the operation mechanism of cells, finally inspiring technology breakthroughs in biomedical fields.

Chaetophora lobata is the type species of the polyphyletic genus Chaetophora. Clarification of its species identification, phylogenetic relationships, and plastome characteristics is helpful for ta...

Object High targeting and efficient cytotoxicity toward tumor cells endow NPs excellent anti-tumor activity. Herein, a peptide polymer possessing dual-targeting ability and double therapeutic activity was developed and named TGMF, which can form NPs through self-assembly. It is composed of four functional modules: 1) Active targeting peptide TMTP1 (T) deliver NPs to tumors specifically; 2) Therapeutic peptide GO-203 (G), which can significantly inhibit tumor growth by disrupting the redox balance in cells; 3) A passively targeted enzyme-responsive peptide PLGLGA (M), which can be cleaved specifically by metalloproteinase-2 (MMP-2) highly expressed in the tumor microenvironment (TME); and 4) Hexadecyl (F), which has strong hydrophobicity, can promote the self-assembly of TGMF NPs. Methods Five modular peptide probes, namely, TGF, TMF, TGM, GMF, and TGMF were synthesized and self-assembled into NPs in solution. The characterization, enzyme reactivity, and cytotoxicity of NPs were evaluated in vitro, and the pharmacokinetics, bio-distribution, anti-tumor activity of NPs were investigated in vivo. In addition, transcriptome sequencing identified the intracellular signaling pathway-related genes involved in the anti-tumor effect of TGMF. Results Upon enzyme cleavage, two types of nanostructure, NPs and nanofibers (NFs), were detected under TEM. Moreover, the cytotoxicity and anti-invasion activity of TGMF against tumor cells used were strongest among the five modular probes examined in vitro. TGMF increased reactive oxygen species (ROS) levels in cytoplasm and produced numerous NFs in extracellular interval and intracellular space. Transcriptome sequencing revealed that TGMF caused 446 genes' down-regulation and 270 genes' up-regulation in HeLa cells. In vivo, TGMF has a good anti-tumor effect, effectively prolonging the survival time of HeLa-tumor-bearing mice without systemic side effects. Conclusion Integration of multiple functional modules into NPs could be a promising strategy for the future of nanomedicine design towards tumor treatment.

Nanoparticle drug delivery system (NDDS) is quite different from the widely studied traditional chemotherapy which suffers from drug resistance and side effect. NDDS offers the straightforward solution to the chemotherapy problem and provides an opportunity to monitor the drug delivery process in real time. In this vein, we developed one NDDS, namely Py-TPE/siRNA@PMP, to relieve resistance and side effects during chemotherapy against ovarian cancer. The Py-TPE/siRNA@PMP is a multifunctional polymeric nanoparticle contained several parts as follows: (1) a nanoparticle (NP) self-assembled by reduction-sensitive paclitaxel polymeric prodrug (PMP); (2) the glutathione (GSH)-responsive release of paclitaxel (PTX) for the suppression of ovarian cancer cells; (3) the P-glycoprotein (P-gp) siRNA for restoring the sensitivity of chemo-resistant tumor cells to chemotherapy; (4) the positively charged aggregation-induced emission fluorogen (AIEgen) Py-TPE for tumor imaging and promoting encapsulation of siRNA into the nanoparticle. Methods: The Py-TPE/siRNA@PMP nanoparticles were prepared by self-assembly method and characterized by the UV-Vis absorption spectra, zeta potentials, TEM image, stability assay and hydrodynamic size distributions. The combinational therapeutic effects of Py-TPE/siRNA@PMP on overcoming chemotherapy resistance were explored both in vitro and in vivo. Result: The Py-TPE/siRNA@PMP exhibited an average hydrodynamic size with a good stability. Meanwhile they gave rise to the remarkable chemotoxicity performances in vitro and suppressed the tumors growth in both SKOV-3/PTX (PTX resistance) subcutaneous and intraperitoneal metastasis tumor models. The investigations on ovarian cancer patient-derived xenografts (PDX) model revealed that Py-TPE/siRNA@PMP was able to effectively overcome their chemo-resistance with minimal side effects. Conclusion: Our findings demonstrated the Py-TPE/siRNA@PMP as a promising agent for the highly efficient treatment of PTX-resistant cells and overcoming the shortage of chemotherapy in ovarian cancer.

Shuguang Xu,1 Jinjing Tu,1 Liang Zhang,1 Yinv Chen,1 Xiaoqi Dong,1 Xiaohui Chi,2,* Hao Xu2,* 1Department of Pulmonary and Critical Care Medicine, Ningbo Medical Center Lihuili Hospital, Ningbo, People’s Republic of China; 2Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hao Xu; Xiaohui Chi, Email xuhao930523@163.com; chixiaohui@zju.edu.cnPurpose: Nosocomial infections caused by New Delhi metallo-β-lactamase (NDM)-producing bacteria are prevalent worldwide. However, such diseases caused by NDM-producing Aeromonas caviae had never been reported. Our study aimed to elucidate the genomic characteristics of NDM-1-producing A. caviae isolated from hospital patients.Methods: Bacterial genomic features and possible origins were assessed by whole-genome sequencing (WGS) and phylogenetic analysis. Subsequent investigations include antimicrobial susceptibility testing and multilocus sequence typing (MLST).Results: We identified here two NDM-1-producing A. caviae isolates from bacteremia. Susceptibility testing showed that two isolates were multi-drug resistant and shared a similar resistance profile and were only sensitive to amikacin and trimethoprim/sulfamethoxazole. Both A. caviae isolates carry the carbapenem resistance gene blaNDM-1 and also have antibiotic resistance genes such as β-lactams, AmpC enzymes, macrolides, aminoglycosides, and quinolones. S1-PFGE and Southern blot analysis were negative. Whole-genome sequencing and comparative analysis revealed that these two isolates shared a close relationship.Conclusion: To the best of our knowledge, this work describes the first detection of non-plasmid encoded blaNDM-1 in A. caviae. The A. caviae isolated in this study has a broad drug resistance spectrum. Phenotypic and molecular analysis indicated the two isolates belong to the same clone. Routine genomic surveillance of this species is now necessary to effectively curb the further dissemination of carbapenem-resistant bacteria in the region.Keywords: Aeromonas caviae, New Delhi metallo-β-lactamase, whole-genome sequencing, SNP, phylogenetic analysis

Downregulating programmed cell death ligand 1(PD-L1) protein levels in tumor cells is an effective way to achieve immune system activation for oncology treatment, but current strategies are inadequate. Here, we design a caged peptide-AIEgen probe (GCP) to self-assemble with miR-140 forming GCP/miR-140 nanoparticles. After entering tumor cells, GCP/miR-140 disassembles in the presence of Cathepsin B (CB) and releases caged GO203 peptide, miR-140 and PyTPA. Peptide decages in the highly reductive intracellular environment and binds to mucin 1 (MUC1), thereby downregulating the expression of PD-L1. Meanwhile, miR-140 reduces PD-L1 expression by targeting downregulation of PD-L1 mRNA. Under the action of PyTPA-mediated photodynamic therapy (PDT), tumor-associated antigens are released, triggering immune cell attack on tumor cells. This multiple mechanism-based strategy of deeply downregulating PD-L1 in tumor cells activates the immune system and thus achieves effective immunotherapy.

Perchlorate is a widely detected environmental contaminant in surface and underground water, that seriously impacts human health by inhibiting the uptake of thyroidal radioiodine. Perchlorate reduction due to saline lake microorganisms is not as well understood as that in marine environments. In this study, we enriched a perchlorate-reducing microbial consortium collected from saline lake sediments and found that the perchlorate reduction kinetics of the enriched consortium fit the Michaelis-Menten kinetics well, with a maximum specific substrate reduction rate (q

A novel coupled yeast-sludge system (CYSS) was constructed by the yeast Candida sp. PNY integrated with activated sludge to treat non-sterile mainstream wastewater. After 240-day cultivation, compared with single activated sludge, simultaneous removal efficiency of total organic carbon (TOC), nitrogen and phosphorus increased by 19.5% (176.34 mg TOC g

Filamentous green algae Chaetophorales present numerous taxonomic problems as many other green algae. Phylogenetic analyses based on nuclear genes have limited solutions. Studies with appropriate chloroplast molecular markers may solve this problems; however, suitable molecular markers for the order Chaetophorales are still unknown. In this study, 50 chloroplast genomes of Chlorophyceae, including 15 of Chaetophorales, were subjected to single protein-coding gene phylogenetic analyses, and substitution rate and evolutionary rate assays, and PCR amplification verification was conducted to screen the suitable molecular markers. Phylogenetic analyses of three chloroplast representative genes (psaB, tufA, and rbcL) amplified from 124 strains of Chaetophorales showed that phylogenetic relationships were not improved by increasing the number of samples, implying that the genes themselves, rather than limited samples, were the reason for the unsupported Topology I. Seven genes (atpF, atpI, ccsA, cemA, chlB, psbB, and rpl2) with robust support were selected to be the most suitable molecular markers for phylogenetic analyses of Chaetophorales, and the concatenated seven genes could replace the time-consuming and labor-intensive phylogenetic analyses based on chloroplast genome to some extent. To further solve the taxonomic problems of Chaetophorales, suitable chloroplast markers combined with more taxon-rich approach could be helpful and efficient.

The study aimed to explore the influencing factors on critical coronavirus disease 2019 (COVID-19) patients’ prognosis and to construct a nomogram model to predict the mortality risk. We retrospectively analyzed the demographic data and corresponding laboratory biomarkers of 102 critical COVID-19 patients with a residence time ≥ 24 h and divided patients into survival and death groups according to their prognosis. Multiple logistic regression analysis was performed to assess risk factors for critical COVID-19 patients and a nomogram was constructed based on the screened risk factors. Logistic regression analysis showed that advanced age, high peripheral white blood cell count (WBC), low lymphocyte count (L), low platelet count (PLT), and high-sensitivity C-reactive protein (hs-CRP) were associated with critical COVID-19 patients mortality risk (p < 0.05) and these were integrated into the nomogram model. Nomogram analysis showed that the total factor score ranged from 179 to 270 while the corresponding mortality risk ranged from 0.05 to 0.95. Findings from this study suggest advanced age, high WBC, high hs-CRP, low L, and low PLT are risk factors for death in critical COVID-19 patients. The Nomogram model is helpful for timely intervention to reduce mortality in critical COVID-19 patients.

Red blood cell (RBC)-mimicking nanoparticles (NPs) offer a promising platform for drug delivery because of their prolonged circulation time, reduced immunogenicity and specific targeting ability. Herein, we report the design and preparation of RBC membrane-bound NPs (M@AP), for tumoral photodynamic-immunotherapy. The M@AP is formed by self-assembly of the positively charged aggregation-induced emission luminogen (AIEgen) (named P2-PPh3) and the negatively charged polyinosinic : polycytidylic acid (Poly(I : C)), followed by RBC membrane encapsulation. P2-PPh3 is an AIE-active conjugated polyelectrolyte with additional photosensitizing ability for photodynamic therapy (PDT), while Poly(I : C) serves as an immune-stimulant to stimulate both tumor and immune cells to activate immunity, and thus reduces tumor cell viability. When applied in tumor-bearing mice, the M@AP NPs are enriched in both the tumor region as a result of an enhanced permeability and retention (EPR) effect, and the spleen because of the homing effect of the RBC-mimicking shell. Upon light irradiation, P2-PPh3 promotes strong ROS generation in tumor cells, inducing the release of tumor antigens (TA). The anti-tumor immunity is further enhanced by the presence of Poly(I : C) in M@AP. Thus, this strategy combines the PDT properties of the AIE-active polyelectrolyte and immunotherapy properties of Poly(I : C) to achieve synergistic activation of the immune system for anti-tumor activity, providing a novel strategy for tumor treatment., Immunotherapy has great potential, but the response of some tumors to immunotherapy is not high. Herein, we developed a biomimetic red cell membrane loaded with aggregation-induced emission luminogen and polyinosinic:polycytidylic acid nanoparticles to enhance the efficacy of tumor immunotherapy.

A new Candida tropicalis that simultaneously remove nitrogen and phosphorus, and degrade organic matters was isolated. Three continuous stirred tank reactors inoculated with C. tropicalis, activated sludge, and their co-existing system in aerobic condition were operated for 150 days. Results demonstrated that the inoculation of C. tropicalis in the co-existing system remarkably improved the carbon, nitrogen, and phosphorus removal efficiencies. The co-existing system had increased carbon, nitrogen, and phosphorus removal efficiencies (92%, 73%, and 63%, respectively); decreased biomass (reduced from 1200 mg/L to 500 mg/L); and C. tropicalis as the dominant strain. The relative abundance of traditional nitrogen- and phosphorus-removing microorganisms, such as Mycobacterium, Flavonifactor, and Devsia, increased in the co-existing system. Metagenomic analysis showed that the presence of the PCYT2, EPT1, and phnPP genes and more complexed metabolism pathways in the co-existing system might be responsible for the more activated metabolism process.

Immunotherapy maintains the cancer-immunity cycle via re-activating the immune system, so as to achieve the purpose of anti-tumor. However, the response rate of current tumor immunotherapy strategies is still low. Even the most reported immune checkpoint block (ICB), the objective response rate (ORR) is only about 10-30%. Here, aiming at obtaining a higher response rate, we designed a cascade amplification nanocomposite consisting of the immune adjuvant polyinosinic:polycytidylic acid [Poly (I:C)] and aggregation-induced emission luminogen (AIEgen)-modified modular peptide (named PMRA). The PMRA includes

Introduction Prehypertension is highly prevalent. However, very few studies have evaluated the association of various metabolic risk factors in those with prehypertension and, more importantly, possible differences based on gender. Material and methods Data of clinical characteristics were collected from 3891 subjects. Risk factors were analyzed by multiple logistic regression analysis. The areas under receiver operating characteristic curves were compared to assess the discriminatory value of metabolic parameters for predicting prehypertension. Results The incidence of prehypertension was 55.9% (66.9% of men, 41.1% of women). Prehypertensives showed clusters of metabolic associations including changes in the levels of plasma high-density lipoprotein cholesterol (OR = 1.550), triglycerides (OR = 1.141) and fasting blood glucose (OR = 1.320) after adjusting for age, sex, body mass index and smoking. The metabolic associations also showed differences based on gender. For instance, higher total cholesterol (OR = 1.602) was the most evident risk factor in men with prehypertension, while higher triglycerides (OR = 1.314) and lower high-density lipoprotein cholesterol (OR = 1.729) were the main risk factors in women. Conclusions Our study suggests that risk associations of prehypertension show gender differences. These results emphasize the importance of health education, active management of blood pressure and timely and effective treatment of abnormal lipid profile in subjects with prehypertension.

Triclosan (TCS) is applied in a wide range of pharmaceutical and personal care products to prevent or reduce bacterial growth. In this study, the effects of TCS on phosphate removal and bacterial community shifts of activated sludge, especially on functional bacteria variation, were investigated. Compared with the control group (R-control), the treatment group (R-TCS) with 100 μg/L TCS inhibited the microbial growth. In addition, the phosphorus removal efficiency of PO43−-P and total phosphorus removal rates declined by 15.99% and 7.81%, respectively. Proteobacteria gradually dominated the microorganisms. The growths of Proteobacteria and Bacteroidetes were inhibited when 150 μg/L of TCS was added. Moreover, the differences in the microbial community structures of the R-control and R-TCS groups gradually expanded, no obvious difference was observed in the final stage, and the interrelationships of microbes in the latter weakened. The long-term addition of TCS impairs the growth of polyphosphate-accumulating organisms (PAOs).

Lung cancer is one of the most common malignant diseases and a major threat to public health on a global scale. Non-small-cell lung cancer (NSCLC) has a higher degree of malignancy and a lower 5-year survival rate compared with that of small-cell lung cancer. NSCLC may be mainly divided into two pathological subtypes, adenocarcinoma and squamous cell carcinoma. The aim of the present study was to identify disease genes based on the gene expression profile and the shortest path analysis of weighted functional protein association networks with the existing protein-protein interaction data from the Search Tool for the Retrieval of Interacting Genes. The gene expression profile (GSE10245) was downloaded from the National Center for Biotechnology Information Gene Expression Omnibus database, including 40 lung adenocarcinoma and 18 lung squamous cell carcinoma tissues. A total of 8 disease genes were identified using Naive Bayesian Classifier based on the Maximum Relevance Minimum Redundancy feature selection method following preprocessing. An additional 21 candidate genes were selected using the shortest path analysis with Dijkstra's algorithm. The AURKA and SLC7A2 genes were selected three and two times in the shortest path analysis, respectively. All those genes participate in a number of important pathways, such as oocyte meiosis, cell cycle and cancer pathways with Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. The present findings may provide novel insights into the pathogenesis of NSCLC and enable the development of novel therapeutic strategies. However, further investigation is required to confirm these findings.