Cdh1 plays a protective role in nonalcoholic fatty liver disease by regulating PPAR/PGC-1α signaling pathway.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a significant etiological factor in liver-related diseases, which can lead to severe consequences such as steatohepatitis, cirrhosis and death. Cdh1 is considered as a crucial protein involved in cell cycle regulation. The purpose of this study is to explore the biological role of Cdh1 in NAFLD. MATERIALS AND METHODS: NAFLD cell model was established, and L02 cells and AML12 cells were infected by shRNA lentivirus with Cdh1 knockdown in vitro, and the effect of Cdh1 deletion on cell lipid deposition was evaluated. The effects of Cdh1 deletion on Akt phosphorylation and PPAR/PGC-1α signaling pathway in L02 cells were examined. In addition, the NAFLD mouse model was constructed, and the conditional knockout mice of Cdh1 were selected to verify the results. RESULTS: In vitro experiments showed that the Cdh1 deletion enhanced cell lipid deposition. In vivo experiments showed that conditional knockdown of Cdh1 aggravated fatty degeneration and damage of liver in mice. Cdh1 deletion promotes Akt phosphorylation and inhibits PPAR/PGC-1α signaling pathway in L02 cells. Conditional knockout of Cdh1 down-regulates PPAR/PGC-1α signaling pathway in NAFLD mouse model. CONCLUSION: The deletion of Cdh1 may promote Akt phosphorylation by up-regulating Skp2 and inhibit the PPAR/PGC-1α signaling pathway. Cdh1 serves a protective function in the occurrence and progression of NAFLD.

Blind Source Separation Based on Double-Mutant Butterfly Optimization Algorithm.

The conventional blind source separation independent component analysis method has the problem of low-separation performance. In addition, the basic butterfly optimization algorithm has the problem of insufficient search capability. In order to solve the above problems, an independent component analysis method based on the double-mutant butterfly optimization algorithm (DMBOA) is proposed in this paper. The proposed method employs the kurtosis of the signal as the objective function. By optimizing the objective function, blind source separation of the signals is realized. Based on the original butterfly optimization algorithm, DMBOA introduces dynamic transformation probability and population reconstruction mechanisms to coordinate global and local search, and when the optimization stagnates, the population is reconstructed to increase diversity and avoid falling into local optimization. The differential evolution operator is introduced to mutate at the global position update, and the sine cosine operator is introduced to mutate at the local position update, hence, enhancing the local search capability of the algorithm. To begin, 12 classical benchmark test problems were selected to evaluate the effectiveness of DMBOA. The results reveal that DMBOA outperformed the other benchmark algorithms. Following that, DMBOA was utilized for the blind source separation of mixed image and speech signals. The simulation results show that the DMBOA can realize the blind source separation of an observed signal successfully and achieve higher separation performance than the compared algorithms.

Satellite Network Task Deployment Method Based on SDN and ICN.

With the rapid development of 5G and the Internet of Things, satellite networks are emerging as an indispensable part of realizing wide-area coverage. The growth of the constellation of low-orbit satellites makes it possible to deploy edge computing services in satellite networks. This is, however, challenging due to the topological dynamics and limited resources of satellite networks. To improve the performance of edge computing in a satellite network, we propose a satellite network task deployment method based on SDN (software-defined network) and ICN (information-centric network). In this method, based on the full analysis of satellite network resources, a mission deployment model of a low-orbit satellite network is established. The genetic algorithm is then used to solve the proposed method. Experiments confirm that this method can effectively reduce the response delay of the tasks and the network traffic caused by task processing.

Deep Downregulation of PD-L1 by Caged Peptide-Conjugated AIEgen/miR-140 Nanoparticles for Enhanced Immunotherapy.

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.

Reassessment of suitable markers for taxonomy of Chaetophorales (Chlorophyceae, Chlorophyta) based on chloroplast genomes.

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.

Risk factors for postoperative recovery in oral cancer surgery: A retrospective cohort study.

BACKGROUND: Effective management of oral cancer necessitates a multidisciplinary approach, with surgery playing a pivotal role in treatment. However, there are many risk factors during the perioperative period that affect postoperative recovery. PURPOSE: This study aims to identify the risk factors influencing postoperative recovery in patients undergoing oral cancer surgery, thereby optimizing perioperative management. STUDY DESIGN, SETTING, SAMPLE: A retrospective cohort study was carried out in patients who underwent surgery for oral cancer at The Second Affiliated Hospital Of Zhejiang University School Of Medicine from Jan. to Dec. in 2023. Based on the median length of stay (LOS) of 20.42 days, we divided the study population into DL3W and DM3W groups (DL3W/DM3W: Discharged less/>3 weeks). PREDICTOR VARIABLE: The Predictor variables included sex, age, BMI, smoke, drink, education, settlement, surgery history, tumor history, intra-operative situation, flap details, pathologic stage, treatment and laboratory examination. MAIN OUTCOME VARIABLE: The primary outcome was length of stay (LOS) defined as the days from the start of preoperative preparation to discharge from the hospital. ANALYSES: Descriptive and inferential analyses were performed using the χ2 test, Fisher's exact test and t-test. A P value of 0.05 was deemed as an acceptable statistical significance level. RESULTS: The sample was composed of 103 subjects with a mean age of 59.45 (14.20) and 71 (68.9 %) were male. The median LOS was 20.42 ((range, 10-69) days. The baseline characteristics between the DL3W and DM3W groups were generally balanced. Factors associated with LOS were BMI (95 %CI 1.01-1.15, P = 0.046), intraoperative blood loss (95 %CI 0.;99-1.00, P = 0.002), flap source (P < 0.001), and postoperative fasting time (95 %CI 0.88-0.95, P < 0.001). In the regression model, more intraoperative blood loss and longer postoperative fasting time were associated with increased. LOS and factors BMI and the use of forearm flap were associated with decreased LOS after adjusting the confounding factors. CONCLUSIONS AND RELEVANCE: In the perioperative period for oral cancer patients, optimizing postoperative recovery may be achieved by carefully managing BMI, intraoperative blood loss, flap source, and postoperative fasting time.

Symptom and comorbidity burden in hypertensive patients with obstructive sleep apnea.

Background: Obstructive sleep apnea (OSA) is an important but frequently overlooked risk factor for hypertension (HTN). The prevalence of hypertension is high in patients with OSA, but the differences in clinical symptoms and comorbidities between patients with OSA with hypertension and those with normal blood pressure have not been fully defined. Methods: This study retrospectively analyzed OSA patients diagnosed for the first time in Lihuili Hospital Affiliated to Ningbo University from 2016 to 2020. Patients were divided into an OSA group with hypertension and an OSA group without hypertension. The sociodemographic information, clinical symptoms, comorbidities, and polysomnography results of the two groups were compared. The independent risk factors associated with hypertension in patients with OSA were explored. Results: A total of 1108 patients with OSA initially diagnosed were included in the study, including 387 with hypertension and 721 without. Compared with OSA patients without hypertension, OSA patients with hypertension were older; had a higher body mass index (BMI) and Epworth sleepiness score (ESS); a higher incidence of nocturia; and a higher proportion of diabetes mellitus, coronary heart disease, and cerebrovascular disease. Multivariate analysis showed age (odds ratio [OR]:1.06, 95% confidence interval [CI]:1.04-1.08), BMI (OR:1.17, 95% CI:1.11-1.23), ESS score (OR:0.97, 95%CI: 0.94-1.00) and nocturia symptoms (OR:1.64, 95% CI:1.19-2.27) was independently associated with hypertension in OSA patients, and comorbid diabetes (OR: 3.86, 95% CI: 2.31-6.45), coronary heart disease (OR: 1.90, 95% CI:1.15-3.16), and ischemic stroke (OR: 3.69,95% CI:1.31-10.40) was independently associated with hypertension in OSA patients. Conclusion: Compared to OSA patients with normal blood pressure, OSA patients with hypertension had more significant daytime sleepiness, more frequent nocturnal urination, and a higher risk of diabetes, coronary heart disease, and cerebrovascular disease.

Genome characteristics of a MDR Pseudomonas monteilii carrying a novel VIM-type ß-lactamase, blaVIM-84.

OBJECTIVES: This study aimed to determine the genetic environment and characterize plasmid carrying a novel VIM-type ß-lactamase (VIM-84) in a multidrug-resistant Pseudomonas monteilii isolate obtained from the human gut through whole-genome sequencing. METHODS: DNA extraction of P. monteilii L2757hy was performed using the Genomic DNA Isolation Kit (QIAGEN, Hilden, Germany). Whole-genome sequencing was performed by Illumina NovaSeq 6000 and Oxford Nanopore platforms. The transferability of resistance genes was screened single clonal on MHA plates containing rifampicin and meropenem. Verification was performed using MALDI/TOF-MS and PCR with Pseudomonas aeruginosa PAO1Ri as the recipient strain. RESULTS: L2757hy was identified as P. monteilii through sequencing and ANI analysis. The genome was assigned as ST147 and comprised a 6,130,057 bp chromosome with a GC content of 61.8% and a 49,704 bp plasmid. Several resistance genes, including blaIMP-1, aac(6')-IIa and tmexCD-toprJ, as well as virulence genes such as iroN, and wzaJ, were identified on the chromosome. A novel VIM-type blaVIM-84 was found on the plasmid, which was previously identified in Pseudomonas aeruginosa. Plasmid harboring blaVIM-84 was untypable, and it could be transferred to P. aeruginosa PAO1Ri and was associated with a class I integron with the genetic environment intI1-blaVIM-84-tniR-tniQ-tniB-tniA, likely derived from Tn402. CONCLUSIONS: Our study revealed that the novel blaVIM-84 gene was harbored by P. monteilii rather than P. aeruginosa. We suggested that P. monteilii may serve as a reservoir for resistance genes.

Bio-degraded of sulfamethoxazole by microbial consortia without addition nutrients: Mineralization, nitrogen removal, and proteomic characterization.

Sulfamethoxazole (SMX) is widely employed as an antibiotic, while its residue in environment has become a common public concern. Using 100 mg/L SMX as the sole nutrient source, the acclimated sludge obtained by this study displayed an excellent SMX degradation performance. The addition of SMX resulted in significant microbiological differentiation within the acclimated sludge. Microbacterium (6.6%) was identified as the relatively dominant genera in metabolism group that used SMX as sole carbon source. Highly expressed proteins from this strain strongly suggested its essential role in SMX degradation, while the degradation of SMX by other strains (Thaurea 78%) in co-metabolism group appeared to also rely on this strain. The interactions of differentially expressed proteins were primarily involved in metabolic pathways including TCA cycle and nitrogen metabolism. It is concluded that the sulfonamides might serve not only as the carbon source but also as the nitrogen source in the reactor. A total of 24 intermediates were identified, 13 intermediates were newly reported. The constructed pathway suggested the mineralizing and nitrogen conversion ability towards SMX. Batch experiments also proved that the acclimated sludge displayed ability to biodegrade other sulfonamides, including SM2 and SDZ and SMX-N could be removed completely.

Construction and validation of a prognostic signature based on anoikis-related lncRNAs in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most common type of lung cancer and is characterized by a high death rate and a poor prospect for survival. Anoikis, which is a kind of programmed cell apoptosis, is an important factor in the advancement of tumors. Nonetheless, the function of anoikis-related lncRNAs (ARLRs) in LUAD is still not well understood. The TCGA database was queried for genomic and clinical information. A prognostic signature for ARLRs was established via the use of coexpression analysis and Cox regression. Validation of the model's accuracy was conducted utilizing K-M curves and receiver operating characteristic (ROC) curves, and the signature was utilized to develop a nomogram. LncRNAs were implicated in the progression of tumors, as determined by functional enrichment analysis. There was an improvement in prognosis, increased immune cell infiltration, and higher immune scores among the low-risk patients. Additionally, we found that the two groups had varied anticancer drug sensitivities, which could help guide treatment. The impact of one ARLR, AC026355.2, on migration and invasion was validated by in vitro experiments in LUAD cells. Herein, a new lncRNA signature associated with anoikis was identified and estimated, potentially serving as a prognostic indicator for LUAD patients.

Medical insurance, health risks, and household financial asset allocation: evidence from China household finance survey.

There is a lack of micro evidence on whether medical insurance may optimize the household financial asset allocation by transferring health risk, despite the fact that health risk is a significant component driving families' precautionary savings. This article empirically examines the impact of health risk and social medical insurance on household risky financial asset allocation using a Probit model, based on data from the 2015-2019 China Household Finance Survey (CHFS). The findings indicate that social medical insurance, with its lower level of security, reduces the likelihood, but it can alter households' preferences for risk by lowering marginal effect of health risk. According to the findings of the heterogeneity analysis, people who live in rural and less developed areas are more likely to experience the risk-inhibiting effects of social medical insurance and health risk. The eroding and risk-suppressing impacts of social medical insurance are likewise less pronounced for households headed by women and older people, as is the health risk's suppressive influence on household involvement in risky financial markets. Compared with social medical insurance, commercial medical insurance with a higher level of coverage can dramatically increase household participation in riskier financial markets. This article provides micro-empirical evidence for the household asset allocation effect of medical insurance.

Synthesis and Biological Profiling of Novel Strigolactone Derivatives for Arabidopsis Growth and Development.

The artificially synthesized strigolactone (SL) analogue GR24 is currently the most widely used reference compound in studying the biological functions of SLs. To elucidate the structure-activity relationship and find more promising derivatives with unique molecular profiles, we design and synthesized three series of novel GR24 derivatives and explored their activities in hypocotyl and root development of Arabidopsis. Among the 50 synthesized compounds, A11a, A12a, and A20d were found to have high activities comparable to GR24 for hypocotyl and/or primary root elongation inhibition in Arabidopsis. Some new analogues have been discovered to exhibit unique activities: (1) A20c, A21e, and A21o are specific inhibitors in primary root elongation; (2) A21c, A26c, and A27a exhibit a high promotion effect on Arabidopsis primary root elongation; and (3) A27e possesses the most unique profiles completely opposite to GR24 that promotes both hypocotyl elongation and primary root development. Moreover, we revealed that the AtD14 receptor does not affect the inhibitory effect of SL analogues in Arabidopsis root development. The ligand-receptor interactions for the most representative analogues A11a and A27e were deciphered with a long time scale molecular dynamics simulation study, which provides the molecular basis of their distinct functions, and may help scientists design novel phytohormones.

Microenvironmentally Responsive Chemotherapeutic Prodrugs and CHEK2 Inhibitors Self-Assembled Micelles: Protecting Fertility and Enhancing Chemotherapy.

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, co-delivery micelles (BML@PMP) are developed, 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.

The Imaging Diagnosis of Patients with Shoulder Pain Caused by Sports Injury.

The shoulder joint is the most complex and movable joint of the human body. A variety of diseases can affect the shoulder joint and cause shoulder pain. Sports injuries are an important and common cause of shoulder pain. In the clinical diagnosis of shoulder joint injury, the most commonly used diagnostic methods are X-ray photography and CT imaging, but X-ray photography has poor ability to distinguish shoulder joints and other tiny tissue structures and has a sense of inspiration for shoulder joint injuries. In addition, CT arthrography has a certain risk to the lesion and is easy to form trauma, and it cannot clearly show the shoulder joint structures such as the rotator cuff and the labrum. Therefore, this article conducts MR imaging diagnostic research on patients with shoulder pain caused by sports injuries and plays an important role in imaging. This article deeply studied the clinical manifestations of shoulder joint pain and image processing technology, designed a research experiment on imaging diagnosis results of patients with shoulder joint pain caused by sports injuries, selected 87 patients with shoulder joint pain in a hospital, and analyzed X-ray photography, CT imaging, and MR imaging diagnosis, three methods to compare the diagnostic accuracy and inspection results and conduct an in-depth analysis of the causes of shoulder joint injury. The experimental results showed that there were 87 patients with shoulder joint pain, 65 patients with rotator cuff tear were diagnosed using arthroscopy, and 63 patients with rotator cuff tear were diagnosed by MR imaging. The accuracy rate was as high as 95.6%. Among them, the proportion caused by sports injuries is the highest, reaching 56%.

Advanced simultaneous nitrogen and phosphorus removal for non-sterile wastewater through a novel coupled yeast-sludge system: Performance, microbial interaction, and mechanism.

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-1 d-1), 21.3% (11.25 mg TN g-1 d-1) and 15.0% (6.95 mg TP g-1 d-1), respectively, while the amount of sludge reduced by 50%. Amplicon sequencing analysis showed that the abundance of Nitrosomonas, Nitrospira, Zoogloea, Dechloromonas, and Candidatus Accumulibacter significantly decreased to 0% on Day 200. Abundance of nirS and nirK for denitrification significantly decreased in CYSS by quantitative PCR (qPCR), and the copies of nirS and nirK were 3.37-fold and 1.71-fold decrease from Day 0 to Day 240, respectively. The results of Fluorescence in situ hybridization and co-occurrence network showed that Candida sp. PNY predominated its distribution in CYSS, and strongly connected with environmental variables based on network analysis. Furthermore, this study reconstructed the carbon, nitrogen and phosphorus metabolic pathways of the CYSS based on metagenomics.

Perchlorate reduction kinetics and genome-resolved metagenomics identify metabolic interactions in acclimated saline lake perchlorate-reducing consortia.

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 (qmax) of 0.596 ± 0.001 mg ClO4-/mg DW/h and half-saturation constant (Ks) of 16.549 ± 0.488 mg ClO4-/L. Furthermore, we used improved metagenome binning to reconstruct high-quality metagenome-assembled genomes from the metagenomes of the microbial consortia, including the perchlorate-reducing bacteria (PRB) Dechloromonas agitata and Wolinella succinogenes, with the genome of W. succinogenes harboring complete functional genes for perchlorate reduction being the first recovered. Given that the electrons were directly transferred to the electronic carrier cytochrome c-553 from the quinone pool, the electron transfer pathway of W. succinogenes was shorter and more efficient than the canonical pattern. This finding provides a theoretical basis for microbial remediation of sites contaminated by high concentrations of perchlorate. Metagenomic binning and metatranscriptomic analyses revealed the gene transcription variation of perchlorate reductase pcr and chlorite dismutase cld by PRB and the synergistic metabolic mechanism.

Short-Wavelength Aggregation-Induced Emission Photosensitizers for Solid Tumor Therapy: Enhanced with White-Light Fiber Optic.

Background: 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.

Detection of NDM-1-Positive Aeromonas caviae from Bacteremia by Using Whole-Genome Sequencing.

Purpose: Nosocomial infections caused by New Delhi metallo-ß-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 bla NDM-1 and also have antibiotic resistance genes such as ß-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 bla NDM-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.

Candida tropicalis prompted effectively simultaneous removal of carbon, nitrogen and phosphorus in activated sludge reactor: Microbial community succession and functional characteristics.

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.

A peptide-AIEgen nanocomposite mediated whole cancer immunity cycle-cascade amplification for improved immunotherapy of tumor.

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: DPPA-1 peptide (P), an immune checkpoint inhibitor; PLGLAG peptide (M), a matrix metalloproteinase 2 (MMP-2) responsive sequence to promote the release of DPPA-1; RRRRRRRR peptide (R), for loading the Poly (I:C); PyTPA (A), a photosensitizer with AIE property. In cancer-immunity cycle, photodynamic therapy (PDT) mediated by PyTPA promotes the release of tumor-associated antigens (TAAs), and primes T lymphocytes. The cytokines coming from the stimulation of PDT and Poly (I:C) promote the activation of T lymphocytes. The high level of chemokines in tumor microenvironment promotes immune cells migration and infiltration in tumor with the assistance of PDT. Finally, through ICB with DPPA-1 peptide, T lymphocytes enhance the recognition of tumor cells and killing tumor cells. Immunogenic cell death induces the release of more TAAs, which will enter the next cycle and complete the full-loop again. Taking advantages of whole cancer-immunity cycle, the cascade amplification nanocomposite achieved almost 100% ORR in vivo. This concept of whole cancer-immunity cycle enhanced immunotherapy provides a novel perspective for tumor treatment.