Escalating Carbon Export from High-Elevation Rivers in a Warming Climate.

High-elevation mountains have experienced disproportionately rapid warming, yet the effect of warming on the lateral export of terrestrial carbon to rivers remains poorly explored and understood in these regions. Here, we present a long-term data set of dissolved inorganic carbon (DIC) and a more detailed, short-term data set of DIC, δ13CDIC, and organic carbon from two major rivers of the Qinghai-Tibetan Plateau, the Jinsha River (JSR) and the Yalong River (YLR). In the higher-elevation JSR with ∼51% continuous permafrost coverage, warming (>3 °C) and increasing precipitation coincided with substantially increased DIC concentrations by 35% and fluxes by 110%. In the lower-elevation YLR with ∼14% continuous permafrost, such increases did not occur despite a comparable extent of warming. Riverine concentrations of dissolved and particulate organic carbon increased with discharge (mobilization) in both rivers. In the JSR, DIC concentrations transitioned from dilution (decreasing concentration with discharge) in earlier, colder years to chemostasis (relatively constant concentration) in later, warmer years. This changing pattern, together with lighter δ13CDIC under high discharge, suggests that permafrost thawing boosts DIC production and export via enhancing soil respiration and weathering. These findings reveal the predominant role of warming in altering carbon lateral export by escalating concentrations and fluxes and modifying export patterns.

Novel 2-Amino-1,4-Naphthoquinone Derivatives Induce A549 Cell Death through Autophagy.

A series of 1,4-naphthoquinone derivatives containing were synthesized as anti-cancer agents and the crystal structure of compound 5a was confirmed by X-ray diffraction. In addition, the inhibitory activities against four cancer cell lines (HepG2, A549, K562, and PC-3) were tested, respectively, and compound 5i showed significant cytotoxicity on the A549 cell line with the IC50 of 6.15 µM. Surprisingly, in the following preliminary biological experiments, we found that compound 5i induced autophagy by promoting the recycling of EGFR and signal transduction in the A549 cell, resulting in the activation of the EGFR signal pathway. The potential binding pattern between compound 5i and EGFR tyrosine kinase (PDB ID: 1M17) was also identified by molecular docking. Our research paves the way for further studies and the development of novel and powerful anti-cancer drugs.

pPe Op inhibits HGC-27 cell proliferation, migration and invasion by upregulating miR-30b-5p and down-regulating the Rac1/Cdc42 pathway.

Gastric cancer is the fifth most frequently occurring and the fourth most lethal malignant cancer worldwide. A bioactive protein (pPe Op) from Omphalia lapidescens exhibits significant inhibitory effects on gastric cancer cells. miRNA deep sequencing analysis shows that miR-30b-5p is significantly upregulated in HGC-27 cells treated with pPe Op. Verification results show that the expression level of miR-30b-5p is significantly increased in HGC-27 cells after pPe Op treatment. Additionally, miR-30b-5p is significantly downregulated in clinical gastric cancer tissues compared to that in adjacent normal tissues. Following pPe Op treatment and/or transfection with miR-30b-5p mimic, the proliferation, migration, and invasion of HGC-27 cells are significantly impaired. Immunofluorescence microscopy shows that pPe Op and/or miR-30b-5p destroy(s) microfilaments and microstructures and inhibit(s) the formation of pseudopodia. Bioinformatics analysis, dual-luciferase reporter assay, and western blot analysis confirm that miR-30b-5p downregulates Rac1/Cdc42 expression and activation by targeting RAB22A. Available data indicate that miR-30b-5p plays an anti-gastric cancer role in mediating pPe Op. pPe Op upregulates miR-30b-5p expression, which in turn inhibits RAB22A expression, resulting in a reduction in the expression and activation of Rac1 and Cdc42 and their downstream targets, thus destroying the cytoskeletal structure and inhibiting the proliferation, migration, and invasion of cancer cells.

Antimicrobial activity of omadacycline in vitro against bacteria isolated from 2014 to 2017 in China, a multi-center study.

BACKGROUND: Omadacycline (ZL-2401) is a semi-synthetic derivative of minocycline. It has a broadspectrum activity against Gram-positive and Gram-negative bacteria, and atypical pathogens. The objective of this study was to evaluate the antibacterial activity of omadacycline against recently collected bacterial isolates from Chinese patients. RESULTS: Omadacycline showed potent activity against all Gram-positive pathogens: S. aureus MICs were low regardless of susceptibility to methicillin (methicillin-resistant Staphylococcus aureus, MRSA: N = 97, MIC50/90 0.12/0.25 mg/L, 98.5% susceptible; methicillin-sensitive Staphylococcus aureus, MSSA: N = 100, MIC50/90 0.12/0.12 mg/L, 100.0% susceptible). Omadacycline was also very effective against ß-haemolytic streptococci (MIC50/90, 0.06/0.12 mg/L), viridans group streptococci (MIC50/90,<0.03/0. 06 mg/L), and enterococci (MIC50/90, 0.03/0.12 mg/L). Against S. pneumoniae, omadacycline was highly active regardless of penicillin-resistance (MIC90 0.06 mg/L) and despite the fact that less than 10.0% of these strains were susceptible to tetracycline. Omadacycline exhibited good in vitro activity against Enterobacterales isolates (MIC50/90, 2/8 mg/L), inhibiting 81.7% of the isolates at ≤4 mg/L. M. catarrhalis isolates (MIC50/90, 0.12/0.25 mg/L) were fully susceptible to omadacycline at ≤0.5 mg/L. CONCLUSIONS: Omadacycline showed potent in vitro activity against most common bacterial pathogens, and even against highly resistant problem pathogens, such as MRSA, penicillin-R and tetracycline-R S. pneumoniae and enterococci. The susceptibility rate of Chinese isolates was similar to those reported in other countries, but the decreased activity against K. pneumoniae isolates in the present study should be noted.

Prevalence of nontuberculous mycobacteria in a tertiary hospital in Beijing, China, January 2013 to December 2018.

BACKGROUND: To investigate the species distribution of non-tuberculous mycobacteria (NTM) among tuberculosis (TB) specimens collected from January 2013 to December 2018 at Peking Union Medical Hospital (Beijing), China. NTM species identification was carried out by DNA microarray chip. RESULTS: Mycobacterial species were detected in 1514 specimens from 1508 patients, among which NTM accounted for 37.3% (565/1514), increasing from a proportion of 15.6% in 2013 to 46.1% in 2018 (P < 0.001). Among the 565 NTM positive specimens, the majority (55.2%) were from female patients. Furthermore, patients aged 45-65 years accounted for 49.6% of the total patients tested. Among 223 NTM positive specimens characterized further, the majority (86.2%) were from respiratory tract, whilst 3.6 and 3.1% were from lymph nodes and pus, respectively. Mycobacterium intracellulare (31.8%) and Mycobacterium chelonae / Mycobacterium abscessus (21.5%) were the most frequently detected species, followed by M. avium (13.5%), M. gordonae (11.7%), M. kansasii (7.6%), and others. CONCLUSION: The proportion of NTM among mycobacterial species detected in a tertiary hospital in Beijing, China, increased rapidly from year 2013 to 2018. Middle-aged patients are more likely to be infected with NTM, especially females. Mycobacterium intracellulare and Mycobacterium chelonae/ Mycobacterium abscessus were the most frequently detected NTM pathogens. Accurate and timely identification of NTM is important for diagnosis and treatment.

Rb21.89W32.66O108: An Excellent Mid- and Far-IR Nonlinear-Optical Material with a Wide Band Gap.

IR nonlinear-optical (NLO) crystal is the important device in IR laser technology. Nevertheless, the application of most IR NLO crystals in high-power lasers is always limited by the low laser damage threshold (LDT), which is mainly caused by the narrow optical band gap (Eg). Here, the physical properties of the Rb21.89W32.66O108 (RWO) crystal with a longer absorption cutoff edge and a wide Eg were systematically studied for the first time. A preliminary measurement of the LDT was performed, and the result shows that RWO has a high powder LDT of about 42 times that of AgGaS2. In order to better understand the relationship between the structure and properties, the dipole moments of WO6 octahedra were accurately calculated and analyzed. Meanwhile, it was indicated that RWO exhibits an ideal frequency doubling strength with the type I phase matching. Finally, it was revealed that RWO has great application value as an IR NLO crystal.

Neuropilin1 silencing impairs the proliferation and migration of cells in pancreatic cancer.

BACKGROUND: Neuropilin1 (NRP1) participates in cancer cell proliferation, migration, and metastasis as a multifunctional co-receptor by interacting with multiple signal pathways, but few studies have addressed the precise function of NRP1 in pancreatic cancer (PACA) cells. We aimed to study whether NRP1 gene silencing involved in the proliferation and migration of PACA cells in vitro. METHODS: A lentiviral vector expressing NRP1 shRNA was constructed and transfected into human PACA cells (CFPAC-1 and PANC-1). The expression of NRP1 protein and mRNA was detected by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) assay, respectively. CCK-8 assay, wound healing assay, and transwell assay were conducted to examine the effect of NRP1 silencing on cells proliferation and migration capability. RESULTS: Results of qRT-PCR and Western blot showed successfully established, stably transfected shRNA-NRP1 cells in PACA cells. The proliferation capacity of PACA cells in NRP1 shRNA group was lower significantly than that in the negative control (NC) group (P < .05). The invasion and migration capability of PACA cells in NRP1 shRNA group was lower significantly than that in the NC group (P < .01). CONCLUSIONS: NRP1-shRNA lentiviral interference vectors can effectively decrease NRP1 gene expression in PACA cells, thereby inhibiting cells proliferation and migration, which provides a basis for finding a valuable therapeutic target for PACA therapy.

Comparative transcriptome analysis of human conjunctiva between normal and conjunctivochalasis persons by RNA sequencing.

Conjunctivochalasis (CCH) is a common ocular disease, especially in aged people. However, the molecular mechanism of CCH on transcriptional level has been unclear. In this study, we characterized the transcriptional landscape of human conjunctiva and compared the transcriptome between normal persons (n = 10) and CCH patients (n = 11). Illumina RNA sequencing (RNA-seq) was performed to obtain transcriptional data, and these data were analyzed using various bioinformatics methods, including read mapping, the analysis of gene expression, gene ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genomes (KEGG) metabolic pathway analysis. Additionally, expression patterns of 20 dysregupated genes were validated by qRT-PCR. RNA-seq result showed that clean ratios of 21 samples were more than 95% and more than 92% of all clean reads (32-41 million reads) were mapped to human genome sequence. There were 175 up-regulated genes and 582 down-regulated genes identified in CCH compared to normal persons. Among down-regulated genes in CCH, many genes were related with cell cycle and proliferation, such as BUB1, CCNB1, CCNB2 and CENPA, which might disturb cell growth and proliferation. In addition, several down-regulated genes were associated with keratinization and differentiation of epidermal cells, such as SPRR1A, SPRR1B, and CALML5. In over-expressed genes, CALML6 might play important roles on the development of CCH. The results of qRT-PCR confirmed the accuracy and credibility of RNA-Seq analysis. This study provided a lot of valuable information about pathogenic mechanism of CCH, which could be used to better study CCH in the future.

Enhanced Uranium Immobilization by Phosphate Amendment under Variable Geochemical and Flow Conditions: Insights from Reactive Transport Modeling.

Phosphate amendment has shown promise for enhancing uranium immobilization. The mechanism of the enhancement, however, has remained unclear with contrasting observations under variable environmental conditions. A dual-domain reactive transport model is developed here with constraints from batch and column experimental data to understand the mechanisms and to explore the effectiveness of enhanced U(VI) immobilization under variable geochemical and flow conditions. Modeling results indicate that under low U(VI) conditions in natural waters, phosphate addition promotes U(VI) immobilization through the formation of U(VI)-phosphate ternary surface complexes and the precipitation of calcium phosphate, both decreasing the concentrations of mobile U-Ca-CO3 aqueous complexes. This contrasts with previous hypotheses attributing the immobilization enhancement to U(VI)-phosphate precipitation under experimental conditions with high U(VI). Sensitivity analysis shows that phosphate is effective under relatively low Ca (<0.1 mM) and total inorganic carbon (TIC) (<0.5 mM) conditions, where >60% of U(VI) still remains on sediments after 113 residence times of flushing with low phosphate solutions (<0.1 mM). Under high Ca or TIC conditions, a similar level of U(VI) immobilization can be achieved only when the phosphate concentration is higher than Ca or TIC concentrations. Compared to the strong geochemical effects, flow conditions have relatively limited impacts on U(VI) immobilization. These results explain contrasting field observations on the effectiveness of phosphate amendment and offer capabilities to extrapolate observations to other environmental conditions.

[Causes of orchiectomy: An analysis of 291 cases].

OBJECTIVE: To study the causes of orchiectomy in different age groups. METHODS: We retrospectively reviewed the clinical data about 291 cases of orchiectomy performed between March 1993 and October 2014 and analyzed the causes of surgery and their distribution in different age groups. RESULTS: The main causes of orchiectomy were testicular torsion (45.8%), cryptorchidism (32.5%) and testicular tumor (16.9%) in the patients aged 0-25 years, testicular tumor (42.4%), cryptorchidism (25.9%) and tuberculosis (10.6%) in those aged 26-50 years. Prostate cancer was the leading cause in those aged 51-75 years (77.6%) or older (84.0%)), and testicular tumor was another cause in the 51-75 years old men (10.2%). Prostate cancer, testicular tumor, cryptorchidism, and testicular torsion were the first four causes of orchiectomy between 1993 and 2009. From 2010 to 2014, however, testicular tumor rose to the top while prostate cancer dropped to the fourth place. CONCLUSION: The causes of orchiectomy vary in different age groups. The proportion of castration for prostate cancer patients significantly reduced in the past five years, which might be attributed to the improvement of comprehensive health care service.

Rapid spread of a recently introduced virus (tomato yellow leaf curl virus) and its vector Bemisia tabaci (Hemiptera: Aleyrodidae) in Liaoning Province, China.

In Liaoning Province, China, tomato yellow leaf curl virus (TYLCV) was first detected in 2009 and in only four counties. To quantify the spread of TYLCV and to identify potential factors influencing its spread in Liaoning Province, we assayed for TYLCV within 1,055 whiteflies (Bemisia tabaci (Gennadius) complex) from 74 populations and 29 counties in 2011. The B. tabaci species of these individuals was determined based on molecular markers. TYLCV was found in 13 counties (Donggang, Liaoyang, Kazuo, Lingyuan, Heishan, Liaozhong, Kaiyuan, Taian, Dawa, Dashiqiao, Beizhen, Linghai, and Xingcheng) and was most frequently detected in the central plain. In addition, the percentage of whiteflies with TYLCV was significantly higher in B. tabaci Q than in B. tabaci B but was unrelated to the hosts (pepper, eggplant, tomato, cucumber, and kidney bean) on which the whiteflies had been collected. These results demonstrate that TYLCV has spread rapidly in Liaoning Province since its first detection and suggest that its spread is more closely associated with the introduction of B. tabaci Q than with the species of host plant. These findings also indicate that controls are now needed to reduce the further spread of TYLCV and that these controls should include the management of B. tabaci Q populations.

Construction of a gene signature associated with anoikis to evaluate the prognosis and immune infiltration in patients with colorectal cancer.

Background: Colorectal cancer (CRC) is characterized by a high metastasis rate, leading to poor prognosis and increased mortality. Anoikis, a physiological process, serves as a crucial barrier against metastasis. The objective of this research is to construct a prognostic model for CRC based on genes associated with anoikis. Methods: The study involved differential analysis and univariate Cox analysis of anoikis-related genes (ARGs), resulting in the selection of 47 genes closely associated with prognosis. Subsequently, unsupervised k-means clustering analysis was conducted on all patients to identify distinct clusters. Survival analysis, principal component analysis (PCA), and t-distributed stochastic neighbor embedding (t-SNE) analysis were performed on the different clusters to investigate associations within the clusters. Gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) were utilized to assess metabolic pathway enrichment between the identified clusters. Furthermore, single-sample GSEA (ssGSEA) was applied to explore variations in immune infiltration. Multivariable Cox regression and least absolute shrinkage and selection operator (LASSO) analyses were conducted to construct a risk model based on ten signatures, which enabled the grouping of all samples according to their risk scores. The prognostic value of the model was validated using receiver operating characteristic (ROC) curves, area under the curve (AUC) calculations, and survival curves. Additionally, the expression of candidate genes was validated using quantitative real-time polymerase chain reaction (qRT-PCR). Results: Forty-seven survival-related ARGs were screened out. Somatic mutation analysis showed that these genes revealed a high mutation rate. Based on their expression, two clusters were identified. Cluster B patients exhibited a shortened overall survival and higher immune infiltration. A risk scoring model including ten genes was subsequently developed, which exhibited excellent prognostic predictive ability for CRC, as evidenced by the survival curve, ROC curve, and AUC curve. In addition, a nomogram was developed for predicting 3- and 5-year survival probabilities. The qRT-PCR results indicated the dissimilarities among the ten signatures in the tumor tissues and adjacent tissues of patients with CRC were fundamentally consistent with the analytical findings. Conclusions: This study comprehensively evaluated the prognostic significance of ARGs in CRC. It identified two distinct anoikis-related clusters and examined their respective immune microenvironments. Furthermore, an ARGs signature was developed to effectively predict the prognosis of CRC, thereby establishing a solid foundation for investigating the clinical prognostic role of anoikis in CRC.

Preparation, characterization, and in vitro/vivo evaluation of a multifunctional electrode coating for cochlear implants.

Cochlear implantation (CI) is the primary intervention for patients with sensorineural hearing loss to restore their hearing. However, approximately 90 % of CI recipients experience unexpected fibrosis around the inserted electrode arrays due to acute and chronic inflammation. This fibrosis leads to progressive residual hearing loss. Addressing this complication is crucial for enhancing CI outcomes, yet an effective treatment has not yet been found. In this study, we developed a multifunctional dexamethasone (DXM)-loaded polytrimethylene carbonate (PTMC) electrode coating to mitigate inflammatory reactions and fibrosis after CI. This thin and flexible coating could preserve the mechanical performance of the electrode and reduce the implantation resistance for CI. The in vitro release studies demonstrated the DXM-PTMC coating's efficient drug loading and sustained release capability over 90 days. DXM-PTMC also showed long-term stability, high biocompatibility, and effective anti-inflammatory effects in vitro and in vivo. Compared with the uncoated group, DXM-PTMC coating significantly inhibited the expression of inflammatory factors, such as NO, TNF-α, IL-1ß, and IL-6. DXM-PTMC coating suppressed fibrosis in rat implantation models for 3 weeks by reducing both acute and chronic inflammation. Our findings suggest that DXM-PTMC coating is a novel strategy to improve the outcomes of CI.

Study on the therapeutic effect of Kirschner wire tension band combined with anchor cross-stitch technique in the treatment of comminuted patellar inferopolar fractures.

PURPOSES: Fractures of the inferior patellar pole, unlike other patellar fractures, present challenges for traditional surgical fixation methods. This article introduces the clinical technique and outcomes of using Kirschner wire tension band combined with anchor screw cross-stitch fixation for comminuted inferior patellar pole fractures. METHODS: This retrospective case series study included 14 patients with comminuted inferior patellar pole fractures treated at our institution from September 1, 2020, to April 30, 2022. All patients underwent surgery using the Kirschner wire tension band with anchor screw cross-stitch technique. Follow-up assessments involved postoperative X-rays to evaluate fracture healing, as well as clinical parameters such as healing time, Visual Analog Scale (VAS) scores, range of motion (ROM), and Bostman scores. RESULTS: All patients were followed for an average of over 12 months, with no cases of internal fixation failure. Knee joint stability and function were excellent. X-rays revealed an average healing time of approximately 10.79 ± 1.53 weeks, hospitalization lasted 5.64 ± 1.15 days, surgery took approximately 37.86 ± 5.32 minutes, and intraoperative blood loss was 33.29 ± 8.15 ml. One patient experienced irritation from the internal fixation material. At the final follow-up, the Bostman score averaged 28.29 ± 0.83, knee joint flexion reached 131.07° ± 4.88°, all patients achieved full knee extension, and the VAS score was 0.36 ± 0.63. CONCLUSION: Kirschner wire tension band with anchor screw cross-stitch fixation for comminuted inferior patellar pole fractures delivered satisfactory clinical outcomes. This surgical method, characterized by its simplicity and reliability, is a valuable addition to clinical practice.

Treatment of complex limb fractures with 3D printing technology combined with personalized plates: a retrospective study of case series and literature review.

Background: In recent years, 3D printing technology has made significant strides in the medical field. With the advancement of orthopedics, there is an increasing pursuit of high surgical quality and optimal functional recovery. 3D printing enables the creation of precise physical models of fractures, and customized personalized steel plates can better realign and more comprehensively and securely fix fractures. These technologies improve preoperative diagnosis, simulation, and planning for complex limb fractures, providing patients with better treatment options. Patients and methods: Five typical cases were selected from a pool of numerous patients treated with 3D printing technology combined with personalized custom steel plates at our hospital. These cases were chosen to demonstrate the entire process of printing 3D models and customizing individualized steel plates, including details of the patients' surgeries and treatment procedures. Literature reviews were conducted, with a focus on highlighting the application of 3D printing technology combined with personalized custom steel plates in the treatment of complex limb fractures. Results: 3D printing technology can produce accurate physical models of fractures, and personalized custom plates can achieve better fracture realignment and more comprehensive and robust fixation. These technologies provide patients with better treatment options. Conclusion: The use of 3D printing models and personalized custom steel plates can improve preoperative diagnosis, simulation, and planning for complex limb fractures, realizing personalized medicine. This approach helps reduce surgical time, minimize trauma, enhance treatment outcomes, and improve patient functional recovery.

Design, synthesis, antibacterial evaluation of isopropylamine linked with different substituted phenol and piperazine novel derivatives.

BACKGROUND: Xanthomonas oryzae pv. oryzae (Xoo) is often considered one of the most destructive bacterial pathogens causing bacterial leaf blight (BLB), resulting in significant yield and cost losses in rice. In this study, a series of novel derivatives containing the isopropanolamine moiety linked to various substituted phenols and piperazines were designed, synthesized and screened. RESULTS: Antibacterial activity results showed that most compounds had good inhibitory effects on Xoo, among which compound W2 (EC50 = 2.74 µg mL-1) exhibited the most excellent inhibitory activity, and W2 also had a certain curative effect (35.89%) on rice compared to thiodiazole copper (TC) (21.57%). Scanning electron microscopy (SEM) results indicated that compound W2 could cause rupture of the Xoo cell membrane. Subsequently, proteomics and quantitative real-time polymerase chain reaction revealed that compound W2 affected the physiological processes of Xoo and may exert antibacterial activity by targeting the two-component system pathway. Interestingly, W2 upregulated Xoo's methyltransferase to impact on its pathogenicity. CONCLUSION: The present study offers a promising phenolic-piperazine-sopropanolamine compound as an innovative antibacterial strategy by specifically targeting the two-component system pathway and inducing upregulation of methyltransferase to effectively impact Xoo's pathogenicity. © 2024 Society of Chemical Industry.

Embryonic stem cell-derived extracellular vesicles rejuvenate senescent cells and antagonize aging in mice.

Aging is a degenerative process that leads to tissue dysfunction and death. Embryonic stem cells (ESCs) have great therapeutic potential for age-related diseases due to their capacity for self-renewal and plasticity. However, the use of ESCs in clinical treatment is limited by immune rejection, tumourigenicity and ethical issues. ESC-derived extracellular vesicles (EVs) may provide therapeutic effects that are comparable to those of ESCs while avoiding unwanted effects. Here, we fully evaluate the role of ESC-EVs in rejuvenation in vitro and in vivo. Using RNA sequencing (RNA-Seq) and microRNA sequencing (miRNA-Seq) screening, we found that miR-15b-5p and miR-290a-5p were highly enriched in ESC-EVs, and induced rejuvenation by silencing the Ccn2-mediated AKT/mTOR pathway. These results demonstrate that miR-15b-5p and miR-290a-5p function as potent activators of rejuvenation mediated by ESC-EVs. The rejuvenating effect of ESC-EVs was further investigated in vivo by injection into aged mice. The results showed that ESC-EVs successfully ameliorated the pathological age-related phenotypes and rescued the transcriptome profile of aged mice. Our findings demonstrate that ESC-EVs treatment can rejuvenate senescence both in vitro and in vivo and suggest the therapeutic potential of ESC-EVs as a novel cell-free alternative to ESCs for age-related diseases.

Rapid Phenotypic Antimicrobial Susceptibility Testing Using a Coulter Counter and Proliferation Rate Discrepancy.

The rapid determination of antimicrobial susceptibility and evidence-based antimicrobial prescription is necessary to combat widespread antimicrobial resistance and promote effectively treatment for bacterial infections. This study developed a rapid phenotypic antimicrobial susceptibility determination method competent for seamless clinical implementation. A laboratory-friendly Coulter counter-based antimicrobial susceptibility testing (CAST) was developed and integrated with bacterial incubation, population growth monitoring, and result analysis to quantitatively detect differences in bacterial growth between resistant and susceptible strains following a 2 h exposure to antimicrobial agents. The distinct proliferation rates of the different strains enabled the rapid determination of their antimicrobial susceptibility phenotypes. We evaluated the performance efficacy of CAST for 74 clinically isolated Enterobacteriaceae subjected to 15 antimicrobials. The results were consistent with those obtained via the 24 h broth microdilution method, showing 90.18% absolute categorical agreement.

Syndecan-2 modulates the YAP pathway in epithelial-to-mesenchymal transition-related migration, invasion, and drug resistance in colorectal cancer.

Epithelial-to-mesenchymal transition (EMT) is associated with an invasive phenotype in colorectal cancer (CRC). Here, we examined the roles of YES-associated protein (YAP) and syndecan-2 (SDC2) in EMT-related progression, invasion, metastasis, and drug resistance in CRC. The expression levels of YAP and SDC2 in CRC patient tumor tissue were quantified by PCR and western blotting. EMT-associated characteristics were assessed using Transwell assays and immunohistochemistry. Co-immunoprecipitation, glutathione S-transferase pull-down, and luciferase reporter assays were used to assess interactions between YAP and SDC2. YAP was found to be highly expressed in tumor tissue from 13/16 CRC patients, while SDC2 was highly expressed in the tumor tissue of 12/16 CRC patients. Overexpression of YAP in colon cancer cells led to increased cell viability, invasion, migration, and oxaliplatin resistance demonstrating that YAP plays a role in EMT. In addition, overexpression of YAP led to decreased expression of the large tumor suppressor kinase 1 (LATS1) and mammalian sterile 20-like kinases (MST1/2). Decreased LATS1 expression was associated with increased levels of cell proliferation. Knockdown of YAP by shRNA interference led to decreased cell invasion, migration, and drug resistance in colon cancer cells and reduced tumorigenesis in a mouse xenograft model. Finally, we established that YAP interacted with SDC2, and demonstrated that SDC2 mediated the YAP pathway through the EMT-related factors BMP4, CTGF and FOXM1.

Dppa3 facilitates self-renewal of embryonic stem cells by stabilization of pluripotent factors.

BACKGROUND: Developmental pluripotency-associated 3 (Dppa3, also called Stella or PGC7) is a principal maternal protein specially expressed in pre-implantation embryos, embryonic stem cells (ES cells) and primordial germ cells (PGCs). It plays critical role in the regulating of DNA methylation in zygotes and oocytes. However, the effect of Dppa3 in ES cells on the stability of proteins is still unclear. METHODS: In this study, we first identified the potential interacting proteins with Dppa3 using immunoprecipitation-mass spectrometry (IP-MS). After GO analysis, we further constructed Dppa3-silenced ES cells and ES cell lines overexpressing with different lengths of Dppa3 to explore the mechanisms of Dppa3 on protein stability. RESULTS: IP-MS results showed that Dppa3 interacted with quite a few subunits of 26S proteasome. Full length of Dppa3 stabilized Uhrf1 and Nanog by inhibiting its degradation. Silencing Dppa3 promoted degradation of Nanog protein. CONCLUSIONS: Our results indicated that Dppa3 safeguard the stability of Uhrf1 and Nanog by inhibiting proteasome-associated degradation in ES cells. These findings shed light on new function of Dppa3 in maintaining stability of proteins and provides a valuable resource for understanding the roles of Dppa3 in embryonic stem cells.