Unmasking Bacterial Identities: Exploiting Silver Nanoparticle 'Masks' for Enhanced Raman Scattering in the Rapid Discrimination of Diverse Bacterial Species and Antibiotic-Resistant Strains.

Unraveling bacterial identity through Raman scattering techniques has been persistently challenging due to homogeneously amplified Raman signals across a wide variety of bacterial molecules, predominantly protein- or nucleic acid-mediated. In this study, we present an approach involving the use of silver nanoparticles to completely and uniformly "mask" adsorption on the surface of bacterial molecules through sodium borohydride and sodium chloride. This approach enables the acquisition of enhanced surface-enhanced Raman scattering (SERS) signals from all components on the bacterial surface, facilitating rapid, specific, and label-free bacterial identification. For the first time, we have characterized the identity of a bacterium, including its DNA, metabolites, and cell walls, enabling the accurate differentiation of various bacterial strains, even within the same species. In addition, we embarked on an exploration of the origin and variability patterns of the main characteristic peaks of Gram-positive and Gram-negative bacteria. Significantly, the SERS peak ratio was found to determine the inflection point of accelerated bacterial death upon treatment with antimicrobials. We further applied this platform to identify 15 unique clinical antibiotic-resistant bacterial strains, including five Escherichia coli strains in human urine, a first for Raman technology. This work has profound implications for prompt and accurate identification of bacteria, particularly antibiotic-resistant strains, thereby significantly enhancing clinical diagnostics and antimicrobial treatment strategies.

Solution Combustion Synthesis of Submicron-Sized Titanium Niobium Oxide Anodes for High-Rate and Ultrastable Lithium-Ion Batteries.

Recently, the development of high-rate performance lithium-ion batteries is crucial for the development of next-generation energy storage systems. Nanoarchitecturing of the electrode material is a common strategy to improve the effective Li+ diffusion transport rate. However, this method often results in a reduction of volumetric energy density and battery stability. In this work, we propose a different strategy by synthesizing submicron-sized Ti2Nb10O29 (s-TNO) as a durable high-rate anode material using a facile and scalable solution combustion method, eliminating the dependence nanoarchitectures. The s-TNO electrode material exhibits a large tunnel structure and an excellent pseudocapacitive performance. The results show that this electrode material delivers a commendable reversible capacity of 238.7 mAh g-1 at 0.5 C and retains 78.2% of its capacity after 10,000 cycles at 10 C. This work provides a valuable guide for the synthesis of submicron-structured electrode materials using the solution combustion method, particularly for high-capacity, high-rate, and high-stability electrode materials.

Multi-resource allocation and care sequence assignment in patient management: a stochastic programming approach.

To mitigate outpatient care delivery inefficiencies induced by resource shortages and demand heterogeneity, this paper focuses on the problem of allocating and sequencing multiple medical resources so that patients scheduled for clinical care can experience efficient and coordinated care with minimum total waiting time. We leverage highly granular location data on people and medical resources collected via Real-Time Location System technologies to identify dominant patient care pathways. A novel two-stage Stochastic Mixed Integer Linear Programming model is proposed to determine the optimal patient sequence based on the available resources according to the care pathways that minimize patients' expected total waiting time. The model incorporates the uncertainty in care activity duration via sample average approximation.We employ a Monte Carlo Optimization procedure to determine the appropriate sample size to obtain solutions that provide a good trade-off between approximation accuracy and computational time. Compared to the conventional deterministic model, our proposed model would significantly reduce waiting time for patients in the clinic by 60%, on average, with acceptable computational resource requirements and time complexity. In summary, this paper proposes a computationally efficient formulation for the multi-resource allocation and care sequence assignment optimization problem under uncertainty. It uses continuous assignment decision variables without timestamp and position indices, enabling the data-driven solution of problems with real-time allocation adjustment in a dynamic outpatient environment with complex clinical coordination constraints.

Effect of Special Training Method Based on Breathing Meditation Training on Negative Emotions, Job Burnout and Attention in Operating Room Nurses.

Objective: Nurses working in the operating room face high levels of work stress, leading to an increased prevalence of negative emotions and job burnout. These issues not only affect the well-being of nurses, but may also affect the quality of patient care. Therefore, this study aimed to investigate the effect of a special training method based on breathing meditation on negative emotions, job burnout, attention, and caring ability of operating room nurses. Methods: Taking special training time based on breathing meditation training for nurses in the operating room (June 2022) as the dividing point, operating room nurses with routine training from March 2022 to May 2022 were taken as a pre-training group, and operating room nurses who underwent special training of breathing meditation training from June 2022 to August 2022 were enrolled as a post-training group, special training consisted of breathing meditation training for 8 weeks, once a day, 5 days a week. The same group of nurses (n=35) were enrolled before and after training, and 53 patients in each group were included in the two intervention periods for cooperative study. The scores of nurses' negative emotions [Symptom Checklist (SCL-90), Self-Reporting Questionnaire 20 (SRQ-20)], job burnout scores (emotional consumption, depersonalization and personal accomplishment), attention scores (visual attention, auditory attention and audio-visual combination attention) and caring ability (cognition, courage and patience) before and after training and satisfaction of nursing work were compared between the two groups of patients. Results: The data analysis was performed using SPSS 22.0, with chi-squared tests for categorical data, and t-tests (LSD or paired) for continuous data. The scores of SCL-90 and SRQ-20 of nurses in the post-training group were significantly lower than those in the pre-training group (P < .05). The scores of emotional consumption, depersonalization and, personal accomplishment and total score of job burnout of nurses were significantly lower in a post-training group than those in a pre-training group (P < .05). The visual attention, auditory attention, audio-visual combination attention and total attention score of nurses in the post-training group were significantly higher compared with those in a pre-training group (P < .05). The scores of cognition, courage and patience and total score of the caring ability of nurses in the post-training group were significantly higher than those in the pre-training group (P < .05). The satisfaction of nursing work in post-training group (98.11%) was significantly higher than that in the pre-training group (84.91%) (P < .05). The results indicate that the post-training group of nurses experienced significantly lower levels of emotional distress, reduced job burnout, and improved attention and caring abilities compared to the pre-training group. Additionally, their satisfaction with nursing work significantly increased. These findings suggest that the training program had a positive impact on nurses' mental well-being, job performance, and job satisfaction, which is highly relevant for enhancing the quality of patient care in clinical practice. Conclusion: Our findings are consistent with existing literature on the benefits of meditation and mindfulness training in healthcare Settings. These results have practical implications for both operating room nurses and patient care, indicating that breathing meditation training can be used as an effective tool to improve nurses' mental health and work productivity. Although the study sample was limited, these preliminary results provide valuable directions for future research.

Research on the toxicological prognostic significance of age-related genes in endometrial cancer unveiling key factors in patient prognosis.

This study investigates the influence of aging-related genes on endometrial cancer, a prominent gynecological malignancy with rising incidence and mortality. By analyzing gene expression differences between cancerous and normal endometrial tissues, 42 aging-related genes were identified as differentially expressed. Utilizing the TCGA-UCEC sample, consensus clustering divided the samples into two molecular subgroups, Aging low and Aging high, based on their expression profiles. These subgroups showed distinct prognoses and survival rates, with the Aging high group associated with DNA repair and cell cycle pathways, and the Aging low group showing suppressed metabolic pathways and increased immune cell infiltration, suggesting a potential for better immunotherapy outcomes. Mutation analysis did not find significant differences in mutation frequencies between the groups, but a high Tumor Mutation Burden (TMB) correlated with better prognosis. A risk score model was also developed, showcasing significant prognostic power. Further analysis of the SIX1 gene revealed its overexpression in cancer cells. Drug sensitivity tests indicated that the low-risk group might respond better to chemotherapy. This research underscores the significance of aging-related genes in endometrial cancer, offering insights into their prognostic value and therapeutic potential, which could lead to personalized treatment approaches and enhanced patient management.

Cascade Detrifluoroacetylation, C-S Bond Cleavage, and SN2' Reaction of α,α-Difluorinated Gem-Diols with MBH Esters.

A new SN2' reaction type of Morita-Baylis-Hillman (MBH) ester with sulfonyl anion, generated in situ via detrifluoroacetylation as a nucleophile is developed. Experimental results and DFT calculations disclose that the reaction proceeds via C-C bond cleavage to generate a PhSO2CF2 anion, C-S bond cleavage to generate a sulfonyl anion with the release of CF2 carbene, and an SN2' reaction with the MBH ester. The reaction features operational simplicity, wide substrate scope, high yields, and excellent stereoselectivity, which represents a new reaction mode of fluorinated gem-diols and also provides an efficient way to obtain ß,γ-unsaturated sulfones.

BANF1 promotes glutamate-induced apoptosis of HT-22 hippocampal neurons.

BACKGROUND: Glutamate exposure was fatal to HT-22 neuronal cells that derived from mouse hippocampus. This is often used as a model for hippocampus neurodegeneration in vitro. The targets relevant to glutamate-induced neuronal toxicity is not fully understood. In this study, we aimed to identify crucial factors associated with glutamate-induced cytotoxicity in HT-22 cells. METHODS: HT-22 cells were treated with 7.5 mM glutamate for 24 h and isobaric tags for relative and absolute quantitation (iTRAQ) proteomic analysis conducted to identify the differentially expressed proteins. Differential proteins were subjected to Gene Ontology analyses. Upregulation of barrier to autointegration factor (BANF1/BANF1) protein was confirmed by RT-qPCR and western blotting. Cell viability was measured by CKK-8 and MTT assays. Cell apoptosis rates and intracellular reactive oxygen species (ROS) levels were detected using flow cytometry. RESULTS: A total of 5811 proteins were quantified by iTRAQ, 50 of which were recognized as significantly differential proteins (fold change ≥ 1.5 and P ≤ 0.05); 26 proteins were up-regulated and 24 were down-regulated after exposure to glutamate. GO enrichment analysis showed that the apoptotic signaling pathway was involved in cell death induced by glutamate. BANF1 expression level was markedly increased in HT-22 cells after glutamate treatment. Further, knockdown of BANF1 alleviated glutamate-mediated cell death with lower ROS levels. CONCLUSIONS: In conclusion, we successfully filtered out differential proteins relevant to glutamate-mediated cytotoxicity. BANF1 upregulation promoted glutamate-induced apoptosis of HT-22 cells by enhancing ROS generation.

Dry-Spinning of Artificial Spider Silk Ribbons From Regenerated Natural Spidroin in an Organic Medium.

Natural spider silks with striking performances achieve extensive investigations. Nonetheless, a lack of consensus over the mechanism of the natural spinning hinders the development of artificial spinning methods where the regenerated spider silks generally show poor performances compared with the natural fibers. As is known, the Plateau-Rayleigh instability tends to break solution column into droplets and is considered a main challenge during fiber-spinning. Here in this study, by harnessing the viscoelastic properties of the regenerated spidroin dope solution via organic salt-zinc acetate (ZA), this outcome can be avoided, and dry-spinning of long and mechanically robust regenerated spider silk ribbons can be successfully realized. The as-obtained dry-spun spider silk ribbons show an enhanced modulus up to 14 ± 4 GPa and a toughness of ≈51 ± 9 MJ m-3 after the post-stretching treatment, which is even better than that of the pristine spider silk fibers. This facile and flexible strategy enriches the spinning methodologies which bypass the bottleneck of precisely mimicking the complex natural environment of the glands in spiders, shining a light to the spider-silk-based textile industrial applications.

Prognostic value of ulceration varies across Breslow thicknesses and clinical stages in acral melanoma: a retrospective study.

BACKGROUND: Ulceration is regarded as an adverse prognostic factor and is used together with tumour thickness to subcategorize patients with cutaneous melanoma. However, the prognostic impact of ulceration in acral melanoma (AM) is controversial. OBJECTIVES: To assess the prognostic impact of ulceration in AM and the variability across different Breslow thicknesses and clinical stages. METHODS: A multicentre retrospective study of patients diagnosed with AM between January 2000 and December 2017. Differences in melanoma-specific survival (MSS) between patients with and without ulceration were assessed using the multivariable Cox proportional hazards model and log-rank test. RESULTS: Among 1053 enrolled patients, 62.6% had ulceration. After a median follow-up of 61 months, patients with ulceration had a lower median MSS than those without: 66.1 months, 95% confidence interval (CI) 60.0-86.0 vs. not reached; hazard ratio 1.41, 95% CI 1.09-1.82; P = 0.012. Among patients with thin (≤ 1 mm) melanoma, the survival curves of patients with vs. without ulceration clearly separated over time (P < 0.001). No association between ulceration and MSS was observed for melanomas of thickness > 1 mm (subgroups of T2, T3 and T4; all P-values > 0.05) or patients with stage III disease (hazard ratio 1.09, 95% CI 0.71-1.68, P = 0.39). CONCLUSIONS: Ulceration is an independent negative prognostic factor for patients with AM, but the impact varies across Breslow thicknesses and clinical stages. Ulceration has a significant effect on prognosis for patients with thin (≤ 1 mm) melanoma, but there was no association between ulceration and survival in intermediate/thick AM or stage III AM. What is already known about this topic? Ulceration status is used together with Breslow tumour thickness to subcategorize patients into different stages according to the America Joint Committee on Cancer melanoma staging system. As one distinctive subtype of cutaneous melanoma, acral melanoma (AM) is characterized by poor survival outcomes due to delayed diagnosis and a high prevalence of negative prognostic and genetic features. The prognostic impact of ulceration in AM is still controversial. What does this study add? This was the first large-scale study to assess the prognostic and staging values of ulceration in patients with AM. Ulceration has a significant effect on prognosis for patients with thin (≤1 mm) melanoma, but no association between ulceration and survival was found in intermediate/thick or stage III AM. These findings should be considered when using ulceration-based staging systems.

Evaluation of Gas Adsorption in Nanoporous Shale by Simplified Local Density Model Integrated with Pore Structure and Pore Size Distribution.

Simplified local density (SLD) model has been widely used to describe the gas adsorption behaviors in porous media. However, the slit pore geometry and constant pore width associated with the SLD model may fail to represent the heterogeneous pore network structure in shale. In this study, a new method to integrate the SLD model with the slit and cylindrical pore structures as well as the pore size distribution (PSD) is proposed and validated by the grand canonical Monte Carlo (GCMC) simulations and the experimentally measured adsorption of methane on shale with complex pore network. Comparison results show that reasonably good agreement is achieved between the SLD model and GCMC simulations for both the gas adsorption isotherms and discrete-density profiles in multiwalled carbon nanoslit and nanotube. The corresponding average absolute percentage deviations (% AADs) are below 0.3 and 9.3 for gas adsorption isotherm and discrete-density profile, respectively. In addition, the SLD model coupled with the PSD of slit and cylindrical pores ranging from micro- to macropores properly characterizes the measured excess adsorption of methane on Wolfcamp shale core sample with % AADs between 1.7 and 3.6. It is found that when the pore volume is fixed, the gas adsorption isotherm and gas density profile are heavily dependent on the pore geometry and pore size. Furthermore, integrating the PSD into the SLD model can guarantee the valid identification of the adsorbed- and free-gas regions in flow channels with different sizes based on the gas density profiles. The findings of this study shed light on the effects of pore structure on gas adsorption in nanopores and enable us to precisely evaluate and predict the gas adsorption behaviors in slit and cylindrical pores over a wide range of pore sizes.

Carboxylic Acid O-H Insertion Reaction of ß-Ester Diazos Enabling Synthesis of ß-Acyloxy Esters.

Generation of non-stabilized ß-ester diazos and their applications in carboxylic acid O-H insertion reactions have been reported, which afford ß-acyloxy esters in excellent yield. Varieties of aryl- and alkyl-substituted diazos are well tolerated in this insertion reaction under mild and convenient conditions. Moreover, structural modification of the natural product and molecular drug can also be achieved in this reaction. This protocol not only realizes the reaction involving unstable ß-ester diazos but also provides an efficient strategy for the synthesis of ß-acyloxy esters.

Prognostic impact of Breslow thickness in acral melanoma: A retrospective analysis.

BACKGROUND: Evidence for the prognostic importance of tumor thickness in acral melanoma (AM) patients is limited. OBJECTIVE: The objective of the study was to determine the prognostic impact of Breslow thickness in AM. METHODS: This multicenter study enrolled patients diagnosed with localized AM between January 1, 2000 and December 31, 2017. Melanoma-specific survival (MSS) in different tumor thickness strata (T1-T4: ≤1, >1-2, >2-4, >4 mm, respectively) was estimated by the Kaplan-Meier method. Comparisons were performed by the log-rank test and multivariable Cox regression. RESULTS: A total of 853 patients with clinical N0 (cN0) AM were included in the analysis. The median follow-up time was 60.1 months. The median MSS in patients with T1-T4 disease was not reached, 111.0, 92.8, and 67.1 months, respectively. MSS differed significantly among cN0 patients with T1-T3 AM (log-rank P = .004, .012, <0.001 for T1 vs T2, T2 vs T3, and T1 vs T3, respectively); however, there was no significant difference between T3 and T4 AM (hazard ratio = 0.82, 95% CI, 0.62-1.09). Six-subgroup analyses confirmed that survival outcomes were similar between different subgroups with tumor thickness >2 mm. LIMITATIONS: The limitations were retrospective design and some missing variables. CONCLUSIONS: There was no association between tumor thickness and survival in AM patients with a Breslow thickness >2 mm.

Turbidity prediction of lake-type raw water using random forest model based on meteorological data: A case study of Tai lake, China.

Turbidity is an indication of water quality and enables the growth of pathogenic microorganisms. For drinking water treatment plants (DWTPs), violent fluctuations in turbidity are highly disruptive to operational performance due to the lag in process parameter adjustments. Such risks must be carefully managed to guarantee safe drinking water. Machine learning techniques have been proven to be effective for modeling complex nonlinear environmental systems, and this study adopted such a technique to develop a model for predicting source water turbidity for DWTPs to allow DWTPs to make proactive interventions in advance. A random forest (RF) model used preprocessed (empirical mode decomposition and quartile rejecting) meteorological factors (wind speed, wind direction, air temperature, and rainfall) as the input variables, to establish the turbidity prediction of a lake with significant turbidity in China's South Tai Lake. The modeling process included four main stages: (1) source data analysis, (2) raw data preprocessing, (3) modeling and tuning, and (4) model evaluation. The results of the RF model indicated that the correlation coefficient between the predicted and actual sequences is over 0.7, and more than 55% of the predicted values could control the errors within 20% compared to the actual measured values, suggesting that machine learning techniques are suitable for predicting the turbidity of raw source water. It was found that the RF model can provide a modest performance boost because of its stronger capacity to capture nonlinear interactions in the data. The findings of this study can inform the development of turbidity prediction models using readily available meteorological forecast data. The model can be applied to other DWTPs using similar shallow lakes as water sources.

The Clinicopathological and Survival Profiles Comparison Across Primary Sites in Acral Melanoma.

BACKGROUND: The clinicopathological and survival profiles across primary sites in acral melanoma (AM) are still controversial and unclear. METHODS: This is a multi-center retrospective study. Clinicopathological data of AM patients diagnosed between 1 January 2000 and 31 December 2017 from 6 large tertiary hospitals in China were extracted. Chi square tests were used to compare basic characteristics between primary sites of sole, palm and nail bed. Melanoma-specific survival (MSS) differences based on primary sites were compared by log-rank tests and multivariate Cox regressions were used to identify prognostic factors for MSS. RESULTS: In total, 1157 AM patients were included. The sole group had a more advanced initial stage, deeper Breslow thickness, higher recurrence rate and distant metastases risk (all P < 0.05). The proportion of age < 65 years and ulceration were statistically lower in nail bed and palm groups, respectively. A total of 294 patients underwent sentinel lymph node biopsy and rates of positive SLN status had no statistical difference across primary sites. Among 701 patients with genetic profiles, the mutational frequency of BRAF, C-KIT, and PDGFRA were similar except for NRAS (higher in sole group, P = 0.0102). The median MSS of sole, nail bed and palm patients were 65.0 months, 112.0 months, and not reached, respectively (log-rank P = 0.0053). In multivariate analyses, primary site, initial stage, ulceration and recurrence were the prognostic factors for MSS in overall population, but the statistical significance varied over primary sites. CONCLUSIONS: Substantial clinicopathological and survival heterogeneities exist across different primary sites in the AM population. Sole melanoma has worse prognosis compared with palm and nail bed subtypes.

HIF-1α/SDF-1/CXCR4 axis reduces neuronal apoptosis via enhancing the bone marrow-derived mesenchymal stromal cell migration in rats with traumatic brain injury.

Mesenchymal stromal injection is a promising therapy for traumatic brain injury (TBI). The aim of this study was to explore the effects of the HIF-1α/SDF-1/CXCR4 axis on neuron repair in TBI rats through improving the bone marrow-derived mesenchymalstromal cells (BMSCs) migration. TBI rat models were established. The rats were treated with exogenous SDF-1, and then the neuronal apoptosis in TBI rats was measured. BMSCs from rats were collected, and the roles of NF-κB p65 expression in nuclei, overexpression of SDF-1 and HIF-1α, as well as downregulation of CXCR4 in BMSC migration were identified. HIF-1α- and SDF-1- treated BMSCs were transplanted into TBI rats, after which the neuronal apoptosis and activity of the HIF-1α/SDF-1/CXCR4 axis were detected. Consequently, we found SDF-1 elevated the HIF-1α/SDF-1/CXCR4 activity and presented protective roles in TBI rat hippocampal neurons with reduced neuronal apoptosis. SDF-1 promoted BMSC migration in vitro, and co-effects of SDF-1 and HIF-1α showed strong promotion, while CXCR4 inhibition suppressed BMSC migration. BMSC transplantation activated the HIF-1α/SDF-1/CXCR4 axis and reduced neuronal apoptosis in TBI rats. To conclude, our study demonstrated that the HIF-1α/SDF-1/CXCR4 axis could enhance BMSC migration and alleviate neuronal damage and apoptosis in TBI rats. This study provided novel options for TBI therapy.

The effect of body mass index and creatinine clearance on serum trough concentration of vancomycin in adult patients.

BACKGROUND: The aim of this study was to evaluate the influence of patient body mass index (BMI) and estimated creatinine clearance (CrCl) on serum vancomycin concentrations to define a possible optimal dosage regimen in overweight patients based on data obtained during therapeutic drug monitoring. METHODS: This retrospective study used data collected from January 2017 to January 2019. Adult patients (n = 204) received vancomycin treatment at a dose of 1000 mg every 12 h and underwent serum monitoring. Data collected included patient disease category, sex, age, height, weight, vancomycin concentrations, and serum creatinine. The CrCl values were estimated using the Cockcroft-Gault formula. In this study, statistical comparisons were performed on the results of patients according to serum vancomycin concentration. RESULTS: Serum vancomycin concentration was significantly related to BMI (P <  0.001) and CrCl (P <  0.05) in adult patients. Furthermore, the trough serum vancomycin concentration showed a logarithmic correlation with BMI (R = - 0.5108, 95% CI: - 0.6082 to - 0.3982, P <  0.001) and CrCl (R = - 0.5739, 95% CI: - 0.6616 to - 0.4707, P <  0.001). The multivariate analysis showed that BMI and CrCl are independent contributors to the trough vancomycin concentration. Moreover, some of the patients with higher BMI (≥ 24 kg/m2) met the goal trough concentration after an adjustment from 1000 mg every 12 h to 1000 mg every 8 h. CONCLUSIONS: Serum vancomycin concentration decreases progressively with increasing BMI and the augmentation in CrCl in adult patients. The trough concentration of vancomycin should be continuously monitored for patients with a BMI ≥ 24 kg/m2, and the dosage regimen should be adjusted to reach the target trough concentration in these patients to reduce the impact of BMI.

Inhibition of the type III secretion system by syringaldehyde protects mice from Salmonella enterica serovar Typhimurium.

The invasiveness of Salmonella enterica serovar Typhimurium (S. Typhimurium) is closely associated with the Salmonella pathogenicity island (SPI)-encoded type Ⅲ secretion system (T3SS), which can directly inject a series of effector proteins into eukaryotic cells to enable bacterial infection. In this study, syringaldehyde was identified as an effective inhibitor of the S. Typhimurium T3SS using an effector protein-lactamase fusion reporter system. Syringaldehyde treatment could inhibit the expression of important effector proteins (SipA, SipB and SipC) at a concentration of 0.18 mM without affecting bacterial growth. Additionally, significant inhibition of bacterial invasion and cellular injury was observed following the syringaldehyde treatment in the co-infection system of HeLa cells and S. Typhimurium. Furthermore, treatment with syringaldehyde provided systemic protection to mice infected with S. Typhimurium, reducing mortality (40.00%) and bacterial loads and relieving caecal damage and systemic inflammation. The results presented in this study indicate that syringaldehyde significantly affects T3SS activity and is a potential leading compound for treating S. Typhimurium infections.

Methylation-associated DOK1 and DOK2 down-regulation: Potential biomarkers for predicting adverse prognosis in acute myeloid leukemia.

DOK-1 and DOK-2 (DOK1/2) are closely related members of downstream of tyrosine kinase (DOK) family genes, which are found to be frequently rearranged in several hematopoietic cancers. However, the clinical implications of DOK1/2 in acute myeloid leukemia (AML) remain largely unknown. To investigate the clinical significance, real-time quantitative PCR (RQ-PCR) was carried out to detect DOK1/2 expressions in 125 de novo AML patients and 28 healthy controls. Real-time quantitative methylation-specific PCR (RQ-MSP) and bisulfite sequencing PCR (BSP) were applied to detect DOK1/2 methylation level and density. DOK1/2 expressions were significantly down-regulated in AML patients. The promoters of DOK1/2 were highly hypermethylated and negatively correlated with DOK1/2 expressions in AML patients. In addition, we also confirmed that DOK1/2 expressions could be restored by DOK1/2 demethylation using 5-aza-2'-deoxycytidine in leukemia cell line THP-1. Survival analyses showed that low-expressed DOK1/2 were associated with markedly shorter overall survival and leukemia free survival in both whole-cohort AML and non-M3 AML patients. Multivariate analyses further revealed that DOK1/2 were act as independent prognostic factors in AML patients. These findings indicate that decreased DOK1/2 expressions associated with their promoter hypermethylations predict adverse prognosis in AML.

A potential link between polycystic ovary syndrome and non-alcoholic fatty liver disease: an update meta-analysis.

BACKGROUND: Epidemiological literature regarding the effect of polycystic ovary syndrome (PCOS) as a risk factor for non-alcoholic fatty liver disease (NAFLD) remains inconsistent. Furthermore, it remains debatable whether NAFLD is associated with PCOS as a consequence of shared risk factors or whether PCOS contributes to NAFLD in an independent fashion. Therefore, this meta-analysis was conducted. METHODS: This meta-analysis was conducted in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Relevant studies published before May 2017 were identified and retrieved from PubMed and Web of Science databases. The data were extracted, and the pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: A total of 17 studies were included into the present analysis. Compared to the control group, the risk of NAFLD in the PCOS group was higher (OR = 2.25, 95% CI = 1.95-2.60). When stratified by BMI and geographic location, the results indicated that the frequency of NAFLD risk was significantly higher in obese subjects (OR = 3.01, 95% CI = 1.88-4.82), non-obese subjects (OR = 2.07, 95% CI = 1.12-3.85), subjects from Europe (OR = 2.00, 95% CI = 1.58-2.52), subjects from the Asia-Pacific Region, (OR = 2.32, 95% CI = 1.89-2.84) and subjects from America (OR = 2.96, 95% CI = 1.93-4.55). In addition, PCOS patients with hyperandrogenism (HA) had a significantly higher risk of NAFLD, compared with controls (OR = 3.31, 95% CI = 2.58-4.24). However, there was no association between PCOS patients without HA and higher risk of NAFLD (OR = 1.46; 95% CI =0.55-3.87). The results of this meta-analysis should be interpreted with caution due to the small number of observational studies and possible confounding factors. CONCLUSION: The meta-analysis results suggest that PCOS is significantly associated with high risk of NAFLD. Although this association was independent of obesity and geographic region, it might be correlated with HA.

[Cytological Study in vitro on Co-delivery of siRNA and Paclitaxel within Solid Lipid Nanoparticles to Overcome Multidrug Resistance in Tumors].

Multidrug resistance (MDR) remains the major obstacle to the success of clinical cancer chemotherapy. P-glycoprotein (P-gp), encoded by the MDR1, is an important part with complex mechanisms associated with the MDR. In order to overcome the MDR of tumors, we in the present experimental design incorporated small interfering RNA (siRNA) targeting MDR1 gene and anticancer drug paclitaxel (PTX) into the solid lipid nanoparticles (SLNs) to achieve the combinational therapeutic effects of genetherapy and chemotherapy. In this study, siRNA-PTX-SLNs were successfully prepared. The cytotoxicity of blank SLNs and siRNA-PTX-SLNs in MCF-7 cells and MCF-7/ADR cells were detected by MTT; and the uptake efficiency of PTX in MCF-7/ADR cells were detected via HPLC method; quantitative real-time PCR and flow cytometry were performed to investigate the silencing effect of siRNA-PTX- SLNs on MDR1 gene in MCF-7/ADR cells. The results showed that PTX loaded SLNs could significantly inhibit the growth of tumor cells, and more importantly, the MDR tumor cells treated with siRNA-PTX-SLNs showed the lowest viability. HPLC study showed that SLNs could enhance the cellular uptake for PTX. Meanwhile, siRNA delivered by SLNs significantly decreased the P-gp expression in MDR tumor cells, thus increased the cellular accumulation of rhodamine123 as a P-gp substrate. In conclusion, the MDR1 gene could be silenced by siRNA-PTX-SLNs, which could promote the growth inhibition efficiency of PTX on tumor cells, leading to synergetic effect on MDR tumor therapy.