Search

ObjectivesTo investigate the genetic characteristics and transmission mechanism of the NDM-1-, IMP-4-, and SHV-12-producing multidrug-resistant (MDR) clinical isolate, Citrobacter freundii BC73.MethodsC. freundii BC73 was isolated from a urine specimen of a urological patient diagnosed with bladder cancer at a Chinese teaching hospital. Antimicrobial susceptibility testing was carried out using DL-120E susceptibility cards and DL-96A system. Whole genome sequencing (WGS) of the isolate was performed using the Illumina and Oxford Nanopore platforms to analyze the genetic context of drug resistance genes and plasmid characteristics. The phylogenetic tree was constructed and visualized by KSNP3.0 software and iTOL5.0 online database.ResultsC. freundii isolate BC73 co-carrying blaNDM-1, blaIMP-4 and blaSHV-12 were multidrug-resistant. blaNDM-1 and blaIMP-4 were located on a novel IncFIB-like plasmid, pCFBC1, and an IncN-IncU hybrid plasmid, pCFBC2, respectively. The transferability of blaNDM-1 and blaIMP-4 from C. freundii BC73 to E. coli J53 was successfully demonstrated. The genetic context of the blaNDM-1 and blaIMP-4 genes were ISCR27-groEL-∆groES-cutA-dsbD-trpF-bleMBL-blaNDM-1-∆ISAba125-IS3000 and intI1-blaIMP-4-Kl.pn.13-mobC-IS6100, respectively. Additionally, two extensive transposition units (MGE1 in pCFBC1, MGE2 in pCFBC2) were identified and numerous antimicrobial resistance genes were discovered on it.ConclusionTo our knowledge, our study represents the first characterization of a ST22 C. freundii isolate co-harboring blaNDM-1, blaIMP-4, and blaSHV-12, obtained from a urine sample. The dissemination of this MDR isolate should be of close concern in future clinical surveillance.

Abstract Background Obesity has been confirmed to be associated with infertility. However, the association between metabolically healthy obesity (MHO), a subset of obesity with no metabolic abnormalities, and female infertility has not yet been investigated. This study aimed to examine the association between MHO and the risk of female infertility among United States. Methods This study utilized a cross-sectional design and included 3542 women aged 20–45 years who were selected from the National Health and Nutrition Examination Survey (NHANES) 2013–2020 database. The association between MHO and the risk of infertility was evaluated using risk factor–adjusted logistic regression models. Results Higher BMI and WC were associated with increased infertility risk after adjusting for potential confounding factors (OR (95% CI): 1.04(1.02, 1.06), P = 0.001; OR (95% CI): 1.02 (1.01, 1.03), P

Background: Altered epigenetic reprogramming and events contribute to breast cancer (Bca) progression and metastasis. How the epigenetic histone demethylases modulate breast cancer progression remains poorly defined. We aimed to elucidate the biological roles of KDM4A in driving Notch1 activation and Bca progression. Methods: The KDM4A expression in Bca specimens was analyzed using quantitative PCR and immunohistochemical assays. The biological roles of KDM4A were evaluated using wound-healing assays and an in vivo metastasis model. The Chromatin Immunoprecipitation (ChIP)-qPCR assay was used to determine the role of KDM4A in Notch1 regulation. Results: Here, we screened that targeting KDM4A could induce notable cell growth suppression. KDM4A is required for the growth and progression of Bca cells. High KDM4A enhances tumor migration abilities and in vivo lung metastasis. Bioinformatic analysis suggested that KDM4A was highly expressed in tumors and high KDM4A correlates with poor survival outcomes. KDM4A activates Notch1 expressions via directly binding to the promoters and demethylating H3K9me3 modifications. KDM4A inhibition reduces expressions of a list of Notch1 downstream targets, and ectopic expressions of ICN1 could restore the corresponding levels. KDM4A relies on Notch1 signaling to maintain cell growth, migration and self-renewal capacities. Lastly, we divided a panel of cell lines into KDM4Ahigh and KDM4Alow groups. Targeting Notch1 using specific LY3039478 could efficiently suppress cell growth and colony formation abilities of KDM4Ahigh Bca. Conclusion: Taken together, KDM4A could drive Bca progression via triggering the activation of Notch1 pathway by decreasing H3K9me3 levels, highlighting a promising therapeutic target for Bca.

Abstract The recently proposed intelligent reflecting surface (IRS) is considered as a promising technology to combat the propagation distance problem in the future communications. However, due to the lack of quantitative analysis and IRS selection scheme from the perspective of symbol error rate (SER) performance, the performance analysis method of asymptotically tight approximation SER is proposed. Firstly, a communication system model aided by an IRS is established. Then, through the reasonable reconstruction between the reflection coefficient and the link coefficient of IRS, the SNR on the forwarding link of IRS satisfies the harmonic mean form. Finally, based on the calculation method of moment generating function (MGF), the asymptotically tight approximation SER formula of the system with simple structure is derived. The simulation results show that, the asymptotically tight approximation SER formula can accurately describe the system SER performance under the low SNR condition. Before the number of IRS reflection unit increases to a certain value, the system SER performance can be effectively improved. Compared with the AF multi‐relay system, IRS aided system has the slightly better SER performance only in the case of low SNR. Our work will provide the important theoretical basis for the IRS selection in practical communications.

Shiyiwei Shenqi Tablet (SSTs) has been widely used for treatment of different types of cancer including breast cancer. SST has drawn more and more interest due to the low rate of side effects. The aim of this study was to investigate the metabolites in serums of breast cancer patients who received base-line chemotherapy only or combination treatment with SST. An untargeted metabolomics method was developed to investigate the alteration of metabolism in patients’ serums using ultra-high-performance liquid chromatography/Q-exactive Orbitrap mass spectrometry. The patients were separated based on the metabolomics data, and further analyses showed that SST treatment can affect the metabolism of glucose, fatty acid, bile acid and amino acid. In particular, SST treatment significantly reduced some short peptides which are potential tumor neoantigens. This study may provide novel insights into the mechanism underlying interaction between SST and base-line chemotherapy in terms of affecting metabolic pathways and thereby changing metabolic products, which might shed new light for clinical medication.

BackgroundThe naked-eye invisibility of indocyanine green fluorescence limits the application of near-infrared fluorescence imaging (NIR) systems for real-time navigation during sentinel lymph node biopsy (SLNB) in patients with breast cancer undergoing surgery. This study aims to evaluate the effectiveness and safety of a novel NIR system in visualizing indocyanine green fluorescence images in the surgical field and the application value of combined methylene blue (MB) and the novel NIR system in SLNB.MethodsSixty patients with clinical node-negative breast cancer received indocyanine green (ICG) and MB as tracers. Two NIR system instruments, namely, lymphatic fluorescence imaging system (LFIS) designed by the University of Science and Technology of China and vascular imager by Langfang Mingde Medical Biotechnology Co., Ltd. (Langfang vascular imager), were used as navigation assistance to locate sentinel lymph nodes (SLNs). Excising the lymph nodes developed by both MB and ICG by two NIR systems or palpably suspicious as SLNs and undergoing rapid pathological examination.ResultsBoth instruments exhibited 95% (57/60) success for real-time lymphatic fluorescent images. A total of 186 SLNs were identified, of which two were pathologically confirmed as lacking any lymph node tissue. SLN identification rate was 100% (184/184) for MB plus LFIS and 86.96% (160/184) for MB alone. The median number of SLNs identified by LFIS combined with MB was 3 (range of 1–8), which was significantly higher than that by MB alone at 2 (range 1–7) (P

Abstract Background Perkinsosis, a disease caused by the protist Perkinsus, is responsible for mass mortalities of many molluscan species worldwide. The rapid, early and accurate detection of Perkinsus infection is necessary to react to outbreaks, and manage disease transmission. Current methods for diagnosis of Perkinsus spp. are time-consuming or require professional equipment and experienced personnel, rendering them unsuitable for field application. Recombinase polymerase amplification (RPA) assay is a highly sensitive and selective isothermal amplification technique that operates at temperatures of 37–42 °C, requires minimal sample preparation, and is capable of amplifying as low as 1–10 target DNA copies in less than 20 minutes. Methods We report a novel RPA assay that amplifies the internal transcriber spacer (ITS) region of P. beihaiensis, which, followed by rapid detection of amplicons using a lateral flow (LF) strip, enables easy visualization of results by the naked eye. Results The LF-RPA assay successfully amplified P. beihaiensis DNA using a set of primers of 20–25 bp in length. After incubation at 37 °C for 25 min, results were read within 5 min by the naked eye on a lateral flow strip. Our LF-RPA assay was comparably sensitive to qPCR assay, and capable of detecting as few as 26 copies of P. beihaiensis DNA. Cross-amplification occurred with other two Perkinsus species, P. olseni and P. chesapeaki, but not with other potential pathogen taxa in culture environments. We compared the performance of LF-RPA, conventional PCR and qPCR assays on 60 oyster samples. While LF-RPA assay results were 86.2% as sensitive, 77.4% as specific, and generally in agreement with those of conventional PCR results, they were more (93.3%) sensitive, (86.7%) specific, and agreed better with qPCR assay results. Future research should focus on developing simple DNA extraction methods that do not require professional laboratories and complicated extraction procedures, to facilitate application of this LF-RPA assay in the field. Conclusions Our LF-RPA assay provides a rapid and efficient method for detecting species of Perkinsus. This novel assay has potential to be used in field applications.

Abstract Background The role of TMED3 involved in cancers has been seldom described, let alone in breast cancer. To explore the clinicopathological significance of TMED3 expression and the biological roles involved in breast cancer cells, we undertook the study. Methods Immunohistochemistry was performed to observe the pattern of TMED3 expression in breast cancer tissues, totaling 224 cases; followed by detailed statistical analysis between TMED3 expression versus clinicopathological information available. To explore the role of TMED3 involved in the malignant behaviors of breast cancer cells, wound-healing and Transwell assays were conducted to evaluate the variation of migration and invasion of MCF-7 and MDA-MB-231 cells whose TMED3 has been stably silenced using lenti-viral based short hairpin RNA (shRNA) vectors. MTT, clonogenic assay and xenograft nude mice model were undertaken to observe the variation of proliferation both in vitro and in vivo. Results It was shown that elevated TMED3 markedly correlated with ER, PR, Her-2 status, and lymph nodes metastases in addition to significant association with poor overall prognosis. In vitro, TMED3 was shown to promote proliferation, migration and invasion of breast cancer cells. Moreover, miR-188-3p was identified as a novel negative regulator of TMED3 in breast cancer, which can slow down the proliferation, migration and invasion of MCF-7 cells. Results from in vivo xenograft nude mice models showed that lenti-viral based miR-188-3p re-expression can markedly impair the tumor growth. Conclusions Our data define and bolster the oncogenic role of TMED3 in breast cancer.

Enterotoxigenic Escherichia coli (ETEC) is an important cause of diarrhea in human and animal. To determine the mechanism of a bovine lactoferricin-lactoferrampin (LFCA)-encoding Lactobacillus reuteri CO21 (LR-LFCA) to enhance the intestinal mucosal immunity, we used a newborn piglet intestine model to study the intestinal response to ETEC. Pigs were chosen due to the anatomical similarity between the porcine and the human intestine.4-day-old piglets were orally administered with LR-LFCA, LR-con (L. reuteri CO21 transformed with pPG612 plasmid) or phosphate buffered saline (PBS) for three consecutive days, within 21 days after these treatments, we found that LR-LFCA can colonize the intestines of piglets, improve the growth performance, enhance immune response and is beneficial for intestinal health of piglets by improving intestinal barrier function and modulating the composition of gut microbiota. Twenty-one days after, piglets were infected with ETEC K88 for 5 days, we found that oral administration of LR-LFCA to neonatal piglets attenuated ETEC-induced the weight loss of piglets and diarrhea incidence. LR-LFCA decreased the production of inflammatory factors and oxidative stress in intestinal mucosa of ETEC-infected piglets. Additionally, LR-LFCA increased the expression of tight junction proteins in the ileum of ETEC-infected piglets. Using LPS-induced porcine intestinal epithelial cells (IPEC-J2) in vitro, we demonstrated that LR-LFCA-mediated increases in the tight junction proteins might depend on the MLCK pathway; LR-LFCA might increase the anti-inflammatory ability by inhibiting the NF-κB pathway. We also found that LR-LFCA may enhance the antioxidant capacity of piglets by activating the Nrf2/HO-1 pathway. This study demonstrates that LR-LFCA is effective at maintaining intestinal epithelial integrity and host homeostasis as well as at repairing intestinal damage after ETEC infection and is thus a promising alternative therapeutic method for intestinal inflammation.

Ghost imaging is a novel imaging technique that has various advantages over traditional imaging. However, most of the existing works on this technique do not achieve a better resolution than the diffraction limit. In this work, we presented a ghost imaging system with plasmonic structure illumination microscopy that achieved super-resolution imaging. The resolution reaches three to four times of the diffraction limit with surface plasmon polaritons and structure illumination microscopy theory. Since it can produce super-resolution images, this method has important implications in medical fields, such as in microimaging and endoscopy. We used the gamma–gamma intensity-fluctuation model to simulate the ghost imaging system in an atmospheric turbulence channel. By setting proper values of the transmission distance and refractive-index structure parameter, we obtain the peak signal-to-noise ratio (PSNR) performance and symbol-error rate (SER) performance. Finally, the PSNR and SER are used to evaluate the imaging quality, which provides a theoretical model to research the ghost-imaging algorithm further.

Porcine epidemic diarrhea (PED) induced by porcine epidemic diarrhea virus (PEDV) is an intestinal infectious disease in pigs that causes serious economic losses to the pig industry. To develop an effective oral vaccine against PEDV infection, we used a swine-origin Lactobacillus johnsonii (L. johnsonii) as an antigen delivery carrier. A recombinant strain pPG-T7g10-COE/L. johnsonii (L. johnsonii-COE) expressing COE protein (a neutralizing epitope of the viral spike protein) was generated. The immunomodulatory effect on dendritic cell in vitro and immunogenicity in pregnant sows was evaluated following oral administration. L. johnsonii-COE could activate monocyte-derived dendritic cell (MoDC) maturation and triggered cell immune responses. After oral vaccination with L. johnsonii-COE, levels of anti-PEDV-specific serum IgG, IgA, and IgM antibodies as well as mucosal secretory immunoglobulin A (SIgA) antibody were induced in pregnant sows. High levels of PEDV-specific SIgA and IgG antibodies were detected in the maternal milk, which provide effective protection for the piglets against PEDV infection. In summary, oral L. johnsonii-COE was able to efficiently activate anti-PEDV humoral and cellular immune responses, demonstrating potential as a vaccine for use in sows to provide protection of their piglets against PEDV.