Evaluation of the synergistic effect of eravacycline and tigecycline against carbapenemase-producing carbapenem-resistant Klebsiella pneumoniae.

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a substantial healthcare challenge. This study assessed the in vitro efficacy of selected antibiotic combinations against CRKP infections. METHODS: Our research involved the evaluation of 40 clinical isolates of CRKP, with half expressing Klebsiella pneumoniae carbapenemase (KPC) and half producing Metallo-ß-lactamase (MBL), two key enzymes contributing to carbapenem resistance. We determined the minimum inhibitory concentrations (MICs) of four antibiotics: eravacycline, tigecycline, polymyxin-B, and ceftazidime/avibactam. Synergistic interactions between these antibiotic combinations were examined using checkerboard and time-kill analyses. RESULTS: We noted significant differences in the MICs of ceftazidime/avibactam between KPC and MBL isolates. Checkerboard analysis revealed appreciable synergy between combinations of tigecycline (35%) or eravacycline (40%) with polymyxin-B. The synergy rates for the combination of tigecycline or eravacycline with polymyxin-B were similar among the KPC and MBL isolates. These combinations maintained a synergy rate of 70.6% even against polymyxin-B resistant isolates. In contrast, combinations of tigecycline (5%) or eravacycline (10%) with ceftazidime/avibactam showed significantly lower synergy than combinations with polymyxin-B (P < 0.001 and P = 0.002, respectively). Among the MBL CRKP isolates, only one exhibited synergy with eravacycline or tigecycline and ceftazidime/avibactam combinations, and no synergistic activity was identified in the time-kill analysis for these combinations. The combination of eravacycline and polymyxin-B demonstrated the most promising synergy in the time-kill analysis. CONCLUSION: This study provides substantial evidence of a significant synergy when combining tigecycline or eravacycline with polymyxin-B against CRKP strains, including those producing MBL. These results highlight potential therapeutic strategies against CRKP infections.

Lipid metabolism-related long noncoding RNA RP11-817I4.1 promotes fatty acid synthesis and tumor progression in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common types of tumors. The influence of lipid metabolism disruption on the development of HCC has been demonstrated in published studies. AIM: To establish an HCC prognostic model for lipid metabolism-related long non-coding RNAs (LMR-lncRNAs) and conduct in-depth research on the specific role of novel LMR-lncRNAs in HCC. METHODS: Correlation and differential expression analyses of The Cancer Genome Atlas data were used to identify differentially expressed LMR-lncRNAs. Quantitative real-time polymerase chain reaction analysis was used to evaluate the expression of LMR-lncRNAs. Nile red staining was employed to observe intracellular lipid levels. The interaction between RP11-817I4.1, miR-3120-3p, and ATP citrate lyase (ACLY) was validated through the performance of dual-luciferase reporter gene and RIP assays. RESULTS: Three LMR-lncRNAs (negative regulator of antiviral response, RNA transmembrane and coiled-coil domain family 1 antisense RNA 1, and RP11-817I4.1) were identified as predictive markers for HCC patients and were utilized in the construction of risk models. Additionally, proliferation, migration, and invasion were reduced by RP11-817I4.1 knockdown. An increase in lipid levels in HCC cells was significantly induced by RP11-817I4.1 through the miR-3120-3p/ACLY axis. CONCLUSION: LMR-lncRNAs have the capacity to predict the clinical characteristics and prognoses of HCC patients, and the discovery of a novel LMR-lncRNAs, RP11-817I4.1, revealed its role in promoting lipid accumulation, thereby accelerating the onset and progression of HCC.

Marginal zone lymphoma with severe rashes: A case report.

BACKGROUND: Marginal zone lymphoma (MZL) is an indolent subtype of non-Hodgkin lymphoma (NHL), which is rare clinically with severe rashes as the initial symptom. CASE SUMMARY: This study reports a case of MZL with generalized skin rashes accompanied by pruritus and purulent discharge. First-line treatment with rituximab combined with zanubrutinib had poor effects. However, after switching to obinutuzumab combined with zanubrutinib, the case was alleviated, and the rashes disappeared. CONCLUSION: For patients with advanced stage MZL not benefiting from type I anti-CD20 monoclonal antibody (mAb) combination therapy, switching to a type II anti-CD20 mAb combination regimen may be considered. This approach may provide a new perspective in the treatment of MZL.

Disulfidptosis-related lncRNA signatures assess immune microenvironment and drug sensitivity in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is associated with a high mortality rate, where resistance to immunotherapy and chemotherapy plays a crucial role. A newly identified form of cell death called disulfidptosis shows promise, but its biological mechanism in HCC remains uncertain. In this study, a prognostic model was developed for Disulfidptosis-related long non-coding RNAs (DRLs) from 370 HCC patients sourced from TCGA-LIHC, utilizing five key features: AC026356.1, AC073254.1, PXN-AS1 expression, AC026412.3, and AC099066.2. High-risk HCC patients had lower survival, CD4+ T cell infiltration, and elevated immune checkpoint gene expression. Furthermore, based on the features of DRLs, HCC was classified into three subtypes. Notably, patients belonging to different subtypes demonstrated varying overall survival rates, immune cell infiltration patterns, and sensitivity to immune therapy. Moreover, the novel DRL AC026412.3 (HR = 40.207) emerged as the most significant prognostic factor, exhibiting high expression across all HCC cells. Elevated expression of AC026412.3 promoted HCC cell proliferation and induced resistance to gefitinib. In conclusion, we have discovered five DRLs and constructed a prognostic risk model. Our findings validate the correlation between DRL-related prognostic models, tumor subtypes, and the HCC immune microenvironment along with its implications for immunotherapy. Moreover, further investigation into the molecular mechanisms of key biomarkers like AC026412.3 in the future will contribute significantly to advancing our comprehension of HCC's pathogenesis and drug resistance mechanisms.

Multiple Metabolites Derived from Mushrooms and Their Beneficial Effect on Alzheimer's Diseases.

Mushrooms with edible and medicinal potential have received widespread attention because of their diverse biological functions, nutritional value, and delicious taste, which are closely related to their rich active components. To date, many bioactive substances have been identified and purified from mushrooms, including proteins, carbohydrates, phenols, and vitamins. More importantly, molecules derived from mushrooms show great potential to alleviate the pathological manifestations of Alzheimer's disease (AD), which seriously affects the health of elderly people. Compared with current therapeutic strategies aimed at symptomatic improvement, it is particularly important to identify natural products from resource-rich mushrooms that can modify the progression of AD. This review summarizes recent investigations of multiple constituents (carbohydrates, peptides, phenols, etc.) isolated from mushrooms to combat AD. In addition, the underlying molecular mechanisms of mushroom metabolites against AD are discussed. The various mechanisms involved in the antiAD activities of mushroom metabolites include antioxidant and anti-neuroinflammatory effects, apoptosis inhibition, and stimulation of neurite outgrowth, etc. This information will facilitate the application of mushroom-derived products in the treatment of AD. However, isolation of new metabolites from multiple types of mushrooms and further in vivo exploration of the molecular mechanisms underlying their antiAD effect are still required.

Risk factors for mortality after linezolid treatment of vancomycin-resistant Enterococcus bloodstream infection.

OBJECTIVES: We analyzed the risk factors affecting linezolid treatment outcome in vancomycin-resistant Enterococcus (VRE) bloodstream infection (BSI). METHODS: We conducted a multicenter observational study of patients who received linezolid 600 mg every 12 hours for VRE BSI. The primary outcome was 28-day mortality. The estimated area under the concentration-time curve and trough concentration were calculated. Multivariable logistic regression was used for the outcome analysis. RESULTS: A total of 170 patients were included: 114 (67.1%) survived and 56 (32.9%) did not. A total of 26 (18.2%) isolates showed a linezolid minimum inhibitory concentration (MIC) of ≤1 mg/l, 113 (79.0%) of 2 mg/l, and 4 (2.8%) of 4 mg/l. The univariable analysis showed that the linezolid MIC and concentration-time curve/MIC were not associated with mortality (P = 0.95 and P = 0.42, respectively). After adjusting for underlying comorbidity and disease severity, the linezolid dose per body weight (LDBW), body height, and interaction between them were independent risks for mortality. Marginal analysis showed that increasing the LDBW was protective in patients with a body height <160 cm. A trough concentration of >12.2 mg/l was a risk factor for thrombocytopenia. CONCLUSION: The LDBW and body height were interactively associated with clinical outcomes of linezolid treatment for VRE BSI.

The Combination of Daptomycin with Fosfomycin is More Effective than Daptomycin Alone in Reducing Mortality of Vancomycin-Resistant Enterococcal Bloodstream Infections: A Retrospective, Comparative Cohort Study.

INTRODUCTION: High-dose daptomycin-based combinations are recommended for vancomycin-resistant Enterococcus (VRE) bloodstream infection (BSI). Preclinical data have shown a synergistic effect of daptomycin/fosfomycin combinations against VRE. However, clinical studies comparing daptomycin monotherapy with daptomycin/fosfomycin combinations are unavailable. METHODS: An observational study of VRE-BSI was performed between 2010-2021 on patients receiving daptomycin monotherapy (≥ 8 mg/kg) or daptomycin combined with intravenous fosfomycin. Patients treated with concomitant ß-lactam combinations were excluded. The primary outcome was in-hospital mortality. Outcomes were analyzed using multivariable logistic regression and augmented inverse probability weighting (AIPW) analyses. RESULTS: Among 224 patients, 176 received daptomycin monotherapy, and 48 received fosfomycin combinations. The median daptomycin and fosfomycin doses were 9.8 mg/kg and 12 g/day, respectively. In-hospital mortality was 77.3% and 47.9% in the daptomycin monotherapy and fosfomycin combination groups (P < 0.001), respectively. Multivariable logistic regression analysis predicted lower mortality with fosfomycin combination treatment (adjusted odds ratio, 0.35; 95% confidence interval (CI), 0.17-0.73; P = 0.005). AIPW demonstrated a 17.8% reduced mortality with fosfomycin combinations (95% CI, - 30.6- - 4.9%; P = 0.007). The survival benefit was significant, especially among patients with a lower Pitt bacteremia score or fosfomycin minimum inhibitory concentration (MIC) ≤ 64 mg/l. Fosfomycin combination resulted in higher hypernatremia (10.4% vs. 2.8%, P = 0.04) and hypokalemia (33.3% vs. 15.3%, P = 0.009) compared to daptomycin monotherapy. CONCLUSION: The combination of high-dose daptomycin with fosfomycin improved the survival rate of patients with VRE-BSI compared to daptomycin alone. The benefit of the combination was most pronounced for VRE with fosfomycin MIC ≤ 64 mg/l and for patients with a low Pitt bacteremia score.

High-level expression of functional Pfu DNA polymerase recombinant protein by mimicking the enhanced green fluorescence protein gene codon usage.

Pfu DNA polymerase is a vital enzyme in PCR-related experiments. However, it is not easy to achieve high-level expression and high purity through one-step purification. This paper illustrates the method to acquire the full-length open reading frame of Pfu DNA polymerase. Without altering its amino acids, we have modified the codon usage, based on that of the enhanced green fluorescence protein (eGFP), and named it rPfu. The synthesized rPfu gene has been subcloned into the pET28a plasmid and expressed in four Escherichia coli strains without the pLysS plasmid. Three strains have expressed a high level of soluble Pfu DNA polymerase. With the aid of Ni-NTA His•Bind® resin, we could obtain high purity (>95%) soluble recombinant protein. Compared with the commercial, proofreading DNA polymerase, rPfu's bioactivity was 12,987 U/mg; that is, 88,311 U of rPfu could be obtained from 50 mL cultured E. coli. The purified rPfu was able to amplify the length of DNA fragments at least 5.5 kb. The method of increasing soluble protein's yield using the eGFP codon usage may introduce a new possibility to the expression of other soluble recombinant proteins.

The combination of daptomycin with ß-lactam antibiotics is more effective than daptomycin alone for vancomycin-resistant Enterococcus faecium bloodstream infection.

BACKGROUND: The treatment options for vancomycin-resistant Enterococcus (VRE) are limited. A combination of daptomycin (DAP) and ß-lactam (BL) has been suggested; however clinical studies supporting this are lacking. METHODS: Patients with VR E. faecium bacteremia who received ≥ 8 mg/kg daptomycin for ≥ 72 h and initiated ≤ 5 days of culture collection between 2010 and 2021 were included. DAP+BL was defined as receiving BL for ≥ 24 h and within 24 h of DAP initiation. The primary endpoint was a composite clinical success (neither 14-day mortality, microbiological failure, nor change in the anti-VRE regimen). Outcomes were analyzed using multivariable logistic regression and augmented inverse probability weighting (AIPW). RESULTS: A total of 430 patients were enrolled (DAP, n = 45; DAP+BL, n = 385). Clinical success was achieved in 19 (42.2%) patients in the DAP group and 244 (63.4%) in the DAP+BL group [adjusted odds ratio, 3.19; 95% confidence interval (CI) 1.61-6.33; P = 0.001]. Marginal analysis showed that the efficacy of DAP+BL was particularly significant with DAP dose ≥ 9 mg/kg and DAP minimum inhibitory concentration (MIC) ≥ 2 mg/L. With the balance of AIPW, standardized mean clinical success rates for DAP and DAP+BL 37.3% and 63.5%, respectively. The difference between DAP+BL and DAP was of 26.2% in favor of DAP+BL (95% CI, 10.0-42.3%; P = 0.001). CONCLUSIONS: DAP+BL was associated with a significantly higher rate of compositive clinical success than DAP for treatment of VR E. faecium bacteremia. The study suggested BL in combination with high-dose DAP for VR E. faecium bacteremia treatment, especially when VRE showed a high DAP MIC.

Synergistic Effect of Polycarboxylate Superplasticiser and Protein Retarders in Cementitious Materials Containing Na- Montmorillonite: Effect of Addition Methods.

Polycarboxylate superplasticiser (PCE) is notably sensitive towards Na-Montmorillonite (Na-Mmt), an impurity generated from the manufacturing of concrete aggregate due to the chemical intercalation and poor surface adsorption. In order to improve the poor compatibility of PCE, the protein-based retarders were applied as the sacrificial agents, and its synergetic effects in cementitious materials containing Na-Mmt were investigated. The protein-based retarders were applied as the sacrificial agents and its synergetic effects in cementitious materials containing Na-Mmt were investigated. In addition to test rheology, minislump, and setting time, the adsorption behaviour and intercalation were characterised via Total Organic Carbon, X-ray photoelectron spectroscopy, and X-ray diffraction. The results revealed that the incorporation of protein-retarders improved the performance of PCE in terms of workability, and the rheological behaviour of cement with Na-Mmt. Moreover, compared to simultaneous addition, the application of separate addition further increased the workability and improved workability retention, with best dispersion performance obtained by prior adding the retarders, which could be due to the lessened intercalation between the layers of Na-Mmt.

A High Daptomycin Dose Is Associated with Better Bacterial Clearance in Infections Caused by Vancomycin-Resistant Enterococcus faecium Regardless of Daptomycin Minimum Inhibitory Concentration in a Rat Infective Endocarditis Model.

A high daptomycin dose has been suggested for treating vancomycin-resistant Enterococcus faecium (VREf) infections. However, even a 12 mg/kg daptomycin dose might be insufficient for treating VREf with high daptomycin minimum inhibitory concentrations (MICs). Additionally, animal pharmacodynamic and infection models to confirm the efficacy of 12 mg/kg daptomycin are lacking. Male Wistar rats were used for pharmacokinetic profiling and for the development of an infective endocarditis (IE) model. Daptomycin-susceptible dose-dependent VREf (DSE) (MIC of 0.5 mg/L) and daptomycin nonsusceptible VREf (DNSE) (MIC of 8 mg/L) were used for the IE models. The bacterial load of vegetation was the primary outcome and was evaluated after 3 days of daptomycin treatment. Daptomycin administered subcutaneously (s.c.) at 45 and 90 mg/kg, which corresponded to maximum serum concentrations (Cmax) of 122.6 mg/L and 178.5 mg/L, respectively, was equivalent to doses of 8 mg/kg and 12 mg/kg, respectively, in humans. The Cmax/MIC value was correlated with the bacterial load of vegetation after treatment (r = -0.88, P < 0.001). The 90 mg/kg s.c. group showed a significantly lower bacterial load of vegetation (log10 CFU/g) than the 45 mg/kg s.c. group against DSE (0 versus 4.75, P < 0.001) and DNSE (5.12 versus 6.98, P = 0.002). The 90 mg/kg s.c. group did not sterilize the vegetation against DNSE. Although the human equivalent dose of 12 mg/kg daptomycin was more effective than the smaller dose in reducing the bacterial load in DSE and DNSE IE, the dose could not sterilize the vegetation during a DNSE treatment. Further treatment strategies by which to manage severe VREf infections, especially at high daptomycin MICs, are urgently needed. IMPORTANCE Using a rat IE model with pharmacokinetic analysis, the treatment response of VREf IE was found to be daptomycin dose-dependent, presented as Cmax/MIC or as the 24 h area under the concentration-time curve (AUC0-24)/MIC. Daptomycin 90 mg/kg s.c. significantly reduced the bacterial load against DSE and DNSE. It also showed significant activity against DSE and DNSE, compared to 45 mg/kg s.c. Although daptomycin 90 mg/kg can eradicate the bacterial load after 3 days of treatment against DSE, eradication cannot be achieved with 90 mg/kg daptomycin against DNSE.

Daptomycin area under the curve to minimum inhibitory concentration ratio by broth microdilution for predicting the outcome of vancomycin-resistant Enterococcus bloodstream infection.

OBJECTIVES: Different methods are used to determine the minimum inhibitory concentration (MIC) for daptomycin. The threshold is unknown for the free drug area under the concentration-time curve to MIC ratio (fAUC/MIC) of daptomycin using broth microdilution (BMD) to predict outcome of vancomycin-resistant enterococcus (VRE) bacteremia. The MIC testing method which is best for predicting the outcome remains unclear. METHODS: This is a retrospective cohort study. The inclusion criterion was VRE bacteremia treated with ≥ 8 mg/kg of daptomycin. As we aimed to compare different daptomycin MIC testing methods for predicting the clinical outcome of VRE bacteremia, the inclusion criteria included the availability of MIC values for BMD, Etest, and automated antimicrobial susceptibility testing (AST). The primary end point was 28-day mortality. The fAUC/MIC was dichotomized using classification and regression tree analysis for predicting survival. RESULTS: A total of 393 patients were included; 215 survived and 178 died. In the multivariable logistic model for predicting mortality, the dichotomized fAUC/MICs for Etest and AST were 0.508 and 0.065 times as probable, respectively, as that for BMD to minimize information loss. An fAUC/MIC > 75.07 for BMD significantly predicted lower mortality (adjusted odds ratio, 0.53, 95% confidence interval, 0.30-0.95; P = 0.03) after adjusting for underlying disease and bacteremia severity. Using Monte Carlo simulation, none of the doses had a probability of target attainment of ≥ 50% with an MIC of ≥ 2 mg/L. CONCLUSION: The dichotomized threshold for fAUC/MIC for BMD was the best predictor of mortality. An fAUC/MIC > 75.07 for BMD independently predicted better survival.

Minocycline Susceptibility and tetB Gene in Carbapenem-Resistant Acinetobacter baumannii in Taiwan.

Purpose: In this study, we evaluated the minocycline susceptibility rate in carbapenem-resistant Acinetobacter baumannii (CRAB) clinical strains, and the association between tetB carriage and minocycline susceptibility in CRAB. Patients and Methods: A total of 100 genetically unrelated CRAB clinical strains from bloodstream infection were randomly collected from a medical center in Taiwan. An argument for a new minocycline susceptibility breakpoint of 1 mg/L was suggested based on pharmacokinetic (PK) and pharmacodynamic (PD) studies. Strains with minocycline minimum inhibitory concentrations (MICs) of >1 mg/L were classified as PK-PD non-susceptible. TetB carriage was detected by polymerase chain reaction (PCR). Results: Fifty-five (55%) CRAB strains were susceptible to minocycline according to the Clinical and Laboratory Standards Institute (CLSI) criteria, among which 98.2% (54/55) were PK-PD non-susceptible. The minocycline MIC50/90 was 4/16 mg/L. Ninety-seven (97%) strains carried tetB. All of the tetB-positive strains and 66.7% (2/3) of the tetB-negative strains were PK-PD non-susceptible. By statistical analysis, tetB carriage was significantly correlated with PK-PD non-susceptibility (P = 0.03) and a higher minocycline MIC (P = 0.02). The sensitivity and specificity of the tetB PCR for predicting PK-PD non-susceptibility were 98% and 100%, respectively. Conclusion: At our institute, most CRAB strains were PK-PD non-susceptible and most carried tetB gene. Recognizing the minocycline MIC and tetB status may be essential when using minocycline to treat CRAB-related infections.

Association of capsular polysaccharide locus 2 with prognosis of Acinetobacter baumannii bacteraemia.

Acinetobacter baumannii causes healthcare-associated infections worldwide. Capsular polysaccharide (CPS) is shown an important virulence factor of A. baumannii both in vitro and in vivo. Capsule locus 2 (KL2) for CPS is the most common KL type and is associated with carbapenem resistance. It is unclear whether KL2 is related to the clinical outcome of invasive A. baumannii infection. Here we had followed patients with A. baumannii bacteraemia prospectively between 2009 and 2014. One-third of the unduplicated blood isolates were randomly selected each year for microbiological and clinical studies. The KL2 gene cluster was identified using polymerase chain reaction. A total of 148 patients were enrolled randomly. Eighteen isolates (12.2%) carried KL2, and 130 isolates (87.8%) didn't. Compared with non-KL2 isolates, KL2 isolates had significantly higher resistance to imipenem, sulbactam, and tigecycline. Compared with the non-KL group, in the KL2 group, the hospital stay before development of bacteraemia was longer (P < 0.001), a higher percentage had pneumonia (P = 0.004), and the white blood cell count was lower (P = 0.03). Infection with KL2 A. baumannii predicted mortality (adjusted hazard ratio [aHR], 2.03; 95% confidence interval [CI], 1.09-3.78; P = 0.03), independently of the Pitt bacteraemia score (aHR, 1.34; 95% CI, 1.23-1.46; P < 0.001) and leucopenia (aHR, 2.16; 95% CI, 1.30-3.57; P = 0.003). Thrombocytopenia contributed to the effect of KL2 on mortality in bacteraemia (Sobel test P = 0.01). Large-scale studies are warranted to confirm these findings and the underlying mechanisms deserve further investigation.

Identification of Prognostic Biomarkers Originating From the Tumor Stroma of Betel Quid-Associated Oral Cancer Tissues.

BACKGROUND: Partial epithelial-mesenchymal transition (p-EMT) is a distinct clinicopathological feature prevalent in oral cavity tumors of The Cancer Genome Atlas. Located at the invasion front, p-EMT cells require additional support from the tumor stroma for collective cell migration, including track clearing, extracellular matrix remodeling and immune evasion. The pathological roles of otherwise nonmalignant cancer-associated fibroblasts (CAFs) in cancer progression are emerging. METHODS: Gene set enrichment analysis was used to reveal differentially enriched genes and molecular pathways in OC3 and TW2.6 xenograft tissues, representing mesenchymal and p-EMT tumors, respectively. R packages of genomic data science were executed for statistical evaluations and data visualization. Immunohistochemistry and Alcian blue staining were conducted to validate the bioinformatic results. Univariate and multivariate Cox proportional hazards models were performed to identify covariates significantly associated with overall survival in clinical datasets. Kaplan-Meier curves of estimated overall survival were compared for statistical difference using the log-rank test. RESULTS: Compared to mesenchymal OC3 cells, tumor stroma derived from p-EMT TW2.6 cells was significantly enriched in microvessel density, tumor-excluded macrophages, inflammatory CAFs, and extracellular hyaluronan deposition. By translating these results to clinical transcriptomic datasets of oral cancer specimens, including the Puram single-cell RNA-seq cohort comprising ~6000 cells, we identified the expression of stromal TGFBI and HYAL1 as independent poor and protective biomarkers, respectively, for 40 Taiwanese oral cancer tissues that were all derived from betel quid users. In The Cancer Genome Atlas, TGFBI was a poor marker not only for head and neck cancer but also for additional six cancer types and HYAL1 was a good indicator for four tumor cohorts, suggesting common stromal effects existing in different cancer types. CONCLUSIONS: As the tumor stroma coevolves with cancer progression, the cellular origins of molecular markers identified from conventional whole tissue mRNA-based analyses should be cautiously interpreted. By incorporating disease-matched xenograft tissue and single-cell RNA-seq results, we suggested that TGFBI and HYAL1, primarily expressed by stromal CAFs and endothelial cells, respectively, could serve as robust prognostic biomarkers for oral cancer control.

Thermoelastic behavior of skin tissue induced by laser irradiation based on the generalized dual-phase lag model.

This paper analyzes the thermoelastic responses of skin tissue during laser irradiation based on a generalized dual-phase-lag (DPL) model. The method of separation of variables is utilized to obtain the analytical solutions for thermal and mechanical responses. The influences of some crucial parameters on temperature, displacement and stress evolutions are discussed, including the phase lag of heat flux, the phase lag of temperature gradient and the phase lag of laser pulse, the coupling factor between tissue and blood, the porosity of tissue, the equivalent diameter of tissue and the diameter of blood vessels. The generalized DPL bio-heat transfer model predicts different results from those by the classical DPL model and Pennes model. The equivalent diameter of tissue affects the coupling factor between tissue and blood, while the diameter of blood vessels mainly affects the porosity of tissue.

Interfacial hydration determines orientational and functional dimorphism of sterol-derived Raman tags in lipid-coated nanoparticles.

Lipid-coated noble metal nanoparticles (L-NPs) combine the biomimetic surface properties of a self-assembled lipid membrane with the plasmonic properties of a nanoparticle (NP) core. In this work, we investigate derivatives of cholesterol, which can be found in high concentrations in biological membranes, and other terpenoids, as tunable, synthetic platforms to functionalize L-NPs. Side chains of different length and polarity, with a terminal alkyne group as Raman label, are introduced into cholesterol and betulin frameworks. The synthesized tags are shown to coexist in two conformations in the lipid layer of the L-NPs, identified as "head-out" and "head-in" orientations, whose relative ratio is determined by their interactions with the lipid-water hydrogen-bonding network. The orientational dimorphism of the tags introduces orthogonal functionalities into the NP surface for selective targeting and plasmon-enhanced Raman sensing, which is utilized for the identification and Raman imaging of epidermal growth factor receptor-overexpressing cancer cells.

3D-Printed, Portable, Fluorescent-Sensing Platform for Smartphone-Capable Detection of Organophosphorus Residue Using Reaction-Based Aggregation Induced Emission Luminogens.

Development of an easy-to-use, low-cost, household device can help the consumer quickly identify an organophosphorus (OP) residue concentration level. In this work, we demonstrate a 3D-printed, portable, fluorescent-sensing platform for smartphone-capable detection of OPs in vegetables. For development of the proposed device, we utilize the smartphone for capturing the strong thiol-activated fluorescence, which was produced by hydrolysis of OPs in the presence of alkali. The thiol-responsive AIEgen (maleimide-functionalized tetraphenylethylene) was non-emissive in both solution and the solid state but could be readily lighted up by the click addition of thiol to its MI pendant. An android application "Detection" has been developed on the basis of the gray value to analyze the different concentration levels of OPs in vegetable samples. The gray value was linearly related with the concentration of five kinds of organophosphorus residue, ranging from 0 to 20 µg/mL. It was also applied for determination of OPs residue in the leaves of cowpea, celery, and Chinese cabbage. Different from acetylcholinesterase enzyme-based sensors for poor stability under high temperature, the proposed method was a direct detection method for OPs and can be used for rapid monitoring of OPs residue concentration levels before LC-MS analysis.

Theoretical analysis on thermal treatment of skin with repetitive pulses.

Thermal ablation is an efficient method of medical treatment, such as cancer therapy, wound closure, laser cutting, freckle removal and other treatments. In order to guarantee the curative effect and the safety of the patients, the thermal response of the tissue which is subjected to the heat source need to be carefully monitored. However, it is too difficult to achieve real-time monitoring on the full-field temperature. In the present study, efforts were made to build up a theoretical model for the prediction of the thermal response in the human skin. The Dual-Phase-Lag (DPL) bio-heat transfer model and the Henrique's burn assessment model were employed to describe the interaction of multi-pulse heat source and the skin. The repeated multi-pulse laser is a common heat source in the thermal treatment and the thermal responses of the skin would be complicated under the common effects of the non-Fourier effects and the multi-pulse source. The Green's function approach was used to solve the governing equations analytically. The closed-form solution for the temperature distribution of the skin was obtained and the thermal damage was estimated based on the temperature results. The influences of the biological parameters (the phase lags of the heat flux and the temperature gradient) and the heat source parameters (the pulse number and the duty ratio) on the temperature distribution, the burn degree and the irreversible burn depth of the irradiated region were discussed.

Study on habitat suitability and environmental variable thresholds of rare waterbirds.

The conservation level of rare waterbirds reflects the quality of the regional ecological environment and wetlands, and suitable habitat patches and good environmental conditions are bases to support the activities of rare species in habitats. Establishing these conditions is also an important goal of habitat landscape and functional restoration. However, lack of these conditions limits population protection and habitat restoration of rare species. Based on the random forest (RF) algorithm and threshold indicator taxa analysis (TITAN), this paper performed habitat suitability assessment and environmental variable threshold analysis of rare waterbird species in Yancheng coastal wetlands. The results showed that the suitable area proportion of three waterbird species at different habitat sites was less than 20%. The unsuitable area proportions of red-crowned cranes and oriental storks at the CA habitat site were the highest, reaching 86.73% and 85.17%, respectively. In addition, analysis of the importance of environmental variables showed that the main influencing variables affecting the suitable habitat distribution of the three rare waterbirds were habitat type (T_hab), habitat area (A_hab), vegetation coverage (P_fvc), distance to farmland (D_far), distance to reeds (D_ree), ponds density (Ponds), distance to water surface (D_wat) and distance to main roads or seawalls (D_swa). These variables covered the type, area, coverage and distance indicators. With the exception of D_far, Ponds and D_swa, rare waterbirds had response thresholds to each environmental indicator, and these results supported the restoration of landscape structure and function of each habitat site. This study emphasized the importance of foods, water resources and hidden conditions for habitat selection in rare waterbirds. Finally, we proposed the maintenance and restoration patterns of the landscape structure and function of rare waterbird habitats, which are available for other coastal tidal wetlands.