Bacterial infections have caused serious threats to public health due to the antimicrobial resistance in bacteria. Recently, gold nanoclusters (AuNCs) have been extensively investigated for ...biomedical applications because of their superior structural and optical properties. Great efforts have demonstrated that AuNCs conjugated with various surface ligands are promising antimicrobial agents owing to their high biocompatibility, polyvalent effect, easy modification and photothermal stability. In this review, we have highlighted the recent achievements for the utilizations of AuNCs as the antimicrobial agents. We have classified the antimicrobial AuNCs by their surface ligands including small molecules (< 900 Daltons) and macromolecules (> 900 Daltons). Moreover, the antimicrobial activities and mechanisms of AuNCs have been introduced into two main categories of small molecules and macromolecules, respectively. In accordance with the advancements of antimicrobial AuNCs, we further provided conclusions of current challenges and recommendations of future perspectives of antimicrobial AuNCs for fundamental researches and clinical applications.
Objectives
Sarcopenia and systemic inflammation can affect survival of advanced‐stage oral squamous cell carcinoma (OSCC) patients; however, their reciprocal associations with survival outcomes are ...yet to be investigated.
Study Design
Retrospective review at a tertiary cancer center.
Methods
Patients with stage III‐IVB OSCC that underwent surgery and (chemo)radiotherapy at our institution between 2010 and 2015 were reviewed. Skeletal muscle index (SMI) was assessed using computed tomography scans at the C3 vertebra. Sarcopenia was defined at the lowest sex‐specific tertile for SMI. Systemic inflammation was estimated using the modified Glasgow prognostic score (mGPS), which ranges from 0 to 2 based on serum C‐reactive protein and albumin levels. The predictors of overall survival (OS) were evaluated using Cox regression models.
Results
A total of 174 patients were included in the study. The cut‐off values for sarcopenia were set at SMI <52.4 cm2/m2 (men) and < 36.2 cm2/m2 (women) corresponding to the lowest sex‐specific tertile. An mGPS 1–2 was independently associated with sarcopenia (odds ratio: 2.05; 95% confidence interval: 1.06–3.97; P = .03). On multivariate analysis for OS, sarcopenia and mGPS 1–2 independently predicted OS (hazard ratio: 2.12; 95% confidence interval: 1.17–3.85; P = .01 and hazard ratio: 7.85; 95% confidence interval: 3.7–16.65; P < .001, respectively). Patients with both sarcopenia and mGPS 1–2 (vs. neither) had worse OS (hazard ratio: 16.80; 95% confidence interval: 6.01–46.99; P < .001).
Conclusions
Sarcopenia and systemic inflammation may exert a negative synergistic prognostic impact in advanced‐stage OSCC patients.
Level of Evidence
4 Laryngoscope, 131:E1530–E1538, 2021
To investigate the relationship between dry eye and sleep quality in a large community-based Chinese population.
A total of 3,070 participants aged 18-80 were recruited from a community-based study ...in Hangzhou, China during 2016-2017. Sleep quality was evaluated using the Chinese version of the Pittsburgh Sleep Quality Index (CPSQI), and dry eye was evaluated using the Ocular Surface Disease Index (OSDI) questionnaire. Multivariable linear regression and logistic regression models were used to investigate the associations, adjusting for age, smoking, drinking, season, and other potential confounders.
Overall, CPSQI score and sleep dysfunction were significantly associated with mild, moderate, and severe dry eye (ORs for CPSQI score: 1.07, 1.13, 1.14, all p < 0.001; for sleep dysfunction: 1.31, 1.73, 1.66, all p < 0.05). Furthermore, worse OSDI score was presented in participants with worse CPSQI score or sleep dysfunction (CPSQI score > 7) (β: 0.13, 0.54; all p < 0.001). In addition, six of the seven components of CPSQI showed significant associations with dry eye (all p < 0.001), except for the component of sleep medication use. Moreover, we observed significant associations of dry eye in all three subscales of OSDI with CPSQI score and sleep dysfunction.
Our large, community-based study showed a strong association between poor sleep quality and an increased severity of dry eye, suggesting that preventing either one of the discomforts might alleviate the other.
With-no-lysine (WNK) kinases regulate renal sodium-chloride cotransporter (NCC) to maintain body sodium and potassium homeostasis. Gain-of-function mutations of WNK1 and WNK4 in humans lead to a ...Mendelian hypertensive and hyperkalemic disease pseudohypoaldosteronism type II (PHAII). X-ray crystal structure and in vitro studies reveal chloride ion (Cl⁻) binds to a hydrophobic pocket within the kinase domain of WNKs to inhibit its activity. The mechanism is thought to be important for physiological regulation of NCC by extracellular potassium. To test the hypothesis that WNK4 senses the intracellular concentration of Cl⁻ physiologically, we generated knockin mice carrying Cl⁻-insensitive mutant WNK4. These mice displayed hypertension, hyperkalemia, hyperactive NCC, and other features fully recapitulating human and mouse models of PHAII caused by gain-of-function WNK4. Lowering plasma potassium levels by dietary potassium restriction increased NCC activity in wild-type, but not in knockin, mice. NCC activity in knockin mice can be further enhanced by the administration of norepinephrine, a known activator of NCC. Raising plasma potassium by oral gavage of potassium inactivated NCC within 1 hour in wild-type mice, but had no effect in knockin mice. The results provide compelling support for the notion that WNK4 is a bona fide physiological intracellular Cl⁻ sensor and that Cl⁻ regulation of WNK4 underlies the mechanism of regulation of NCC by extracellular potassium.
Corylin is a main compound isolated from Psoralea corylifolia L. (Fabaceae). A variety of pharmacological effects such as antioxidant, anti-proliferation, and anti-inflammatory properties of corylin ...have been reported. Nevertheless, the effect of corylin in microbial infection and sepsis remains unclear. In the present study, we investigated the anti-inflammatory effects of corylin. Our experimental results demonstrated that corylin inhibited the production of TNF-α, IL-6 and NO by both LPS-activated RAW 264.7 cells and LPS-activated murine peritoneal macrophages. Moreover, corylin suppressed the expression levels of iNOS and COX-2, reduced the production of PGE
and HMGB1, blocked the translocation of HMGB1 from the nucleus to cytosol, and decreased the phosphorylation of MAPKs in LPS-activated RAW 264.7 cells as well as suppressed the activity of NF-κB in LPS-activated J-Blue cells. In addition, the administration of corylin reduced the production of NO and TNF-α, decreased LPS-induced liver damage markers (AST and ALT) and kidney damage markers (BUN and CRE), attenuated infiltration of inflammatory cells and tissue damage of lung, liver and kidney, and enhanced the survival rate of LPS-challenged mice. Taken together, these results show the anti-inflammatory properties of corylin on LPS-induced inflammation and sepsis. Corylin could potentially be a novel anti-inflammatory and immunosuppressive drug candidate in the treatment of sepsis and septic shock.
The detection of dyskalemias-hypokalemia and hyperkalemia-currently depends on laboratory tests. Since cardiac tissue is very sensitive to dyskalemia, electrocardiography (ECG) may be able to uncover ...clinically important dyskalemias before laboratory results.
Our study aimed to develop a deep-learning model, ECG12Net, to detect dyskalemias based on ECG presentations and to evaluate the logic and performance of this model.
Spanning from May 2011 to December 2016, 66,321 ECG records with corresponding serum potassium (K
) concentrations were obtained from 40,180 patients admitted to the emergency department. ECG12Net is an 82-layer convolutional neural network that estimates serum K
concentration. Six clinicians-three emergency physicians and three cardiologists-participated in human-machine competition. Sensitivity, specificity, and balance accuracy were used to evaluate the performance of ECG12Net with that of these physicians.
In a human-machine competition including 300 ECGs of different serum K+ concentrations, the area under the curve for detecting hypokalemia and hyperkalemia with ECG12Net was 0.926 and 0.958, respectively, which was significantly better than that of our best clinicians. Moreover, in detecting hypokalemia and hyperkalemia, the sensitivities were 96.7% and 83.3%, respectively, and the specificities were 93.3% and 97.8%, respectively. In a test set including 13,222 ECGs, ECG12Net had a similar performance in terms of sensitivity for severe hypokalemia (95.6%) and severe hyperkalemia (84.5%), with a mean absolute error of 0.531. The specificities for detecting hypokalemia and hyperkalemia were 81.6% and 96.0%, respectively.
A deep-learning model based on a 12-lead ECG may help physicians promptly recognize severe dyskalemias and thereby potentially reduce cardiac events.
The aim of the present study was to determine the antibacterial activities of the phenolic essential oil (EO) compounds hinokitiol, carvacrol, thymol, and menthol against oral pathogens. ...Aggregatibacter actinomycetemcomitans, Streptococcus mutans, Methicillin-resistant Staphylococcus aureus (MRSA), and Escherichia. coli were used in this study. The minimum inhibitory concentrations (MICs), minimum bactericidal concentrations (MBCs), bacterial growth curves, temperature and pH stabilities, and synergistic effects of the liquid and vapor EO compounds were tested. The MIC/MBC of the EO compounds, ranging from the strongest to weakest, were hinokitiol (40-60 μg/mL/40-100 μg/mL), thymol (100-200 μg/mL/200-400 μg/mL), carvacrol (200-400 μg/mL/200-600 μg/mL), and menthol (500-more than 2500 μg/mL/1000-more than 2500 μg/mL). The antibacterial activities of the four EO phenolic compound based on the agar diffusion test and bacterial growth curves showed that the four EO phenolic compounds were stable under different temperatures for 24 h, but the thymol activity decreased when the temperature was higher than 80°C. The combination of liquid carvacrol with thymol did not show any synergistic effects. The activities of the vaporous carvacrol and thymol were inhibited by the presence of water. Continual violent shaking during culture enhanced the activity of menthol. Both liquid and vaporous hinokitiol were stable at different temperatures and pH conditions. The combination of vaporous hinokitiol with zinc oxide did not show synergistic effects. These results showed that the liquid and vapor phases of hinokitiol have strong anti-oral bacteria abilities. Hinokitiol has the potential to be applied in oral health care products, dental materials, and infection controls to exert antimicrobial activity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The relationship between methylglyoxal (MGO) and D-lactate during saikosaponin C (SSC) treatment of mice with accelerated nephrotoxic serum (NTS) nephritis was investigated. NTS nephritis was induced ...by administration of anti-basement membrane antibodies to C57BL/6 mice and three dosages of SSC were administered for 14 days. Proteinuria, blood urea nitrogen, serum creatinine, renal histology, urinary MGO and d-lactate changes were examined. Compared to the NTS control group, the middle dosage (10 mg/kg/day) of SSC significantly alleviated the development of nephritis based on urine protein measurements (34.40 ± 6.85 vs. 17.33 ± 4.79 mg/day, p<0.05). Pathological observation of the glomerular basement membrane (GBM) revealed monocyte infiltration, hypertrophy, and crescents were alleviated, and injury scoring also showed improved efficacy for the middle dose of SSC during nephritis (7.92 ± 1.37 vs. 3.50 ± 1.14, p<0.05). Moreover, the significant decreases in urinary levels of MGO (24.71 ± 3.46 vs. 16.72 ± 2.36 μg/mg, p<0.05) and D-lactate (0.31 ± 0.04 vs. 0.23 ± 0.02 μmol/mg, p<0.05) were consistent with the biochemical and pathological examinations. This study demonstrates that MGO and D-lactate may reflect the extent of damage and the efficacy of SSC in NTS nephritis; further studies are required to enable clinical application.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We assessed the accuracy of species-level identification of two commercially available matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) systems (Bruker ...Biotyper and Vitek MS) and two conventional phenotypic methods (Phoenix 100 YBC and Vitek 2 Yeast ID) with that of rDNA gene sequencing analysis among 200 clinical isolates of commonly encountered yeasts. The correct identification rates of the 200 yeast isolates to species or complex (Candida parapsilosis complex, C. guilliermondii complex and C. rugosa complex) levels by the Bruker Biotyper, Vitek MS (using in vitro devices IVD database), Phoenix 100 YBC and Vitek 2 Yeast ID (Sabouraud's dextrose agar) systems were 92.5%, 79.5%, 89%, and 74%, respectively. An additional 72 isolates of C. parapsilosis complex and 18 from the above 200 isolates (30 in each of C. parapsilosis, C. metapsilosis, and C. orthopsilosis) were also evaluated separately. Bruker Biotyper system could accurately identify all C. parapsilosis complex to species level. Using Vitek 2 MS (IVD) system, all C. parapsilosis but none of C. metapsilosis, or C. orthopsilosis could be accurately identified. Among the 89 yeasts misidentified by the Vitek 2 MS (IVD) system, 39 (43.8%), including 27 C. orthopsilosis isolates, could be correctly identified Using the Vitek MS Plus SARAMIS database for research use only. This resulted in an increase in the rate of correct identification of all yeast isolates (87.5%) by Vitek 2 MS. The two species in C. guilliermondii complex (C. guilliermondii and C. fermentati) isolates were correctly identified by cluster analysis of spectra generated by the Bruker Biotyper system. Based on the results obtained in the current study, MALDI-TOF MS systems present a promising alternative for the routine identification of yeast species, including clinically commonly and rarely encountered yeast species and several species belonging to C. parapsilosis complex, C. guilliermondii complex, and C. rugosa complex.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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