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Exopolysaccharide (EPS) is the main active metabolite of Ganoderma lingzhi in liquid fermentation. In order to increase the content of Ganoderma lingzhi EPS, this study added Vernonia amygdala leaf powder to the fermentation medium, and used single factor experiments and orthogonal experiments to optimize fermentation conditions. Fourier transform infrared spectroscopy was used to characterize the structure of Ganoderma lingzhi EPS, then its antioxidant activity was detected. The single factor experiment found that when the optimal addition amount of Vernonia amygdala leaf powder was 4g/L, the content of EPS increased by 167% compared with the control group. The optimum fermentation conditions of the orthogonal experiment were as follows: Fermentation duration was 12 d, initial pH was 5.0, the rotation speed was 120 r/min, and the addition amount of Vernonia amygdala leaf powder was 4 g/L. Under such a condition, the content of EPS could reach 13.05 g/L. The infrared spectra showed that the major absorption peaks of the Ganoderma lingzhi EPS from the addition of Vernonia amygdala leaf powder were similar to those of the EPS from the control group. The antioxidant activity assay showed that the addition of Vernonia amygdala leaf powder had less effect on the scavenging of ABTS+ radicals by EPS, but enhanced their ability to scavenge DPPH radicals, OH radicals, and ferric ion reduction. The results showed that Vernonia amygdala leaf could effectively increase the content of EPS in Ganoderma lingzhi, which provided a new idea for the efficient production of polysaccharides in Ganoderma lingzhi.

Abstract Background The aim of this study was to prepare a novel 68Ga-labeled pH (low) insertion peptide (pHLIP)-like peptide, YJL-4, and determine its value for the early diagnosis of triple-negative breast cancer (TNBC) via in vivo imaging of tumor-bearing nude mice. The novel peptide YJL-4 was designed using a template-assisted method and synthesized by solid-phase peptide synthesis. After modification with the chelator 1,4,7‑triazacyclononane-N,N′,N″-triacetic acid (NOTA), the peptide was labeled with 68Ga. Then, the biodistribution of 68Ga-YJL-4 in tumor-bearing nude mice was investigated, and the mice were imaged by small animal positron emission tomography (PET). Results The radiochemical yield and radiochemical purity of 68Ga-YJL-4 were 89.5 ± 0.16% and 97.95 ± 0.06%, respectively. The biodistribution of 68Ga-YJL-4 in tumors (5.94 ± 1.27% ID/g, 6.72 ± 1.69% ID/g and 4.54 ± 0.58% ID/g at 1, 2 and 4 h after injection, respectively) was significantly greater than that of the control peptide in tumors at the corresponding time points (P

BackgroundEnfortumab vedotin (EV) is an antibody-drug conjugate (ADC) that has been approved by the FDA for patients with locally advanced or metastatic urothelial carcinoma (UC). This study presents a comprehensive pharmacovigilance analysis of the post-marketing safety profile of EV in the real-world based on the US Food and Drug Administration Adverse Event Reporting System (FAERS).MethodsAdverse event (AE) reports regarding EV between January 2020 and December 2023 were obtained from the FAERS database. The standardized MedDRA query (SMQ) narrow search AEs on the preferred term (PT) level were used. Disproportionality analysis was performed to identify the AE signals for EV with the reporting odds ratio (ROR), proportional reporting ratio (PRR), multi-item gamma Poisson shrinker (MGPS), and Bayesian confidence propagation neural network (BCPNN).ResultsA total of 2,216 reports regarding EV were included in the present study. SMQ analysis results indicated that a stronger strength signal was found in severe cutaneous adverse reactions, retroperitoneal fibrosis, and peripheral neuropathy. A total of 116 significant disproportionality PTs referring to 14 system organ classes (SOCs) were retained by disproportionality analysis, with 49 PTs not listed on the EV drug label. Frequently reported EV-related AEs included rash, peripheral neuropathy, decreased appetite, alopecia, and pruritus. The time to onset of the majority of EV-related AEs was within 30 days (66.05%), with only 0.73% events occurring after 1 year.ConclusionThe disproportionality analysis highlights that dermatologic toxicity and peripheral neuropathy were the major AEs induced by EV. The potential AEs not listed on the drug label were mainly related to gastrointestinal, hepatic, and pulmonary events. Further research is needed to confirm and explore the EV-related AEs in clinical practice.

This study focuses on the difficulty of converting fluorinated rare earth elements into hydroxylated rare earth elements in rare earth melt electrolysis slag (RMES) and proposes the use of a microwave-assisted atmospheric alkaline leaching method for the treatment of RMES. The leaching behavior of RMES under microwave-assisted atmospheric alkaline leaching was studied, and the optimal reaction conditions were determined. Under the conditions of a reaction temperature of 150 °C, initial NaOH concentration of 60 %, NaOH-to-slag mass ratio of 4:1, microwave power of 700 W, reaction time of 120 min, and stirring speed of 300 r/min, the conversion rate of fluorinated rare earths reached 99.17 %. The apparent rate equation of the microwave-assisted atmospheric alkaline leaching process was obtained by leaching kinetic analysis, and the apparent activation energy under this process was calculated to be 54.872 kJ/mol, which was 12.458 kJ/mol lower than that achieved when conventional heating was used for leaching (67.33 kJ/mol).

This is an essay in the field of mining engineering, which summarized the current situation and characteristics of tungsten tailings resources, and expounds the urgency and necessity of comprehensive utilization of tungsten tailings resources under the requirements of current economic development and environmental protection. The research status of recovery of valuable metal and valuable non-metals in tungsten tailings was comprehensively evaluated. The application and application prospects of tungsten tailings in new building materials were introduced in detail. Combined with the current research focus on tungsten tailings resources in China, the development direction of comprehensive utilization of tungsten tailings is proposed.

ABSTRACT The use of combination antibiotics has been useful in the treatment of multidrug-resistant bacterial infections. The synergistic effect of amoxicillin/clavulanate and aztreonam combination against Escherichia coli carrying New Delhi metallo-β-lactamase (NDM) was primarily due to clavulanate inhibiting aztreonam degradation. In the present study, we employed metabolomic analysis to investigate the downstream changes in E. coli after treatment with aztreonam and clavulanate. E. coli metabolomes were compared at 1 and 24 h following treatments with clavulanate (4 µg/mL) and aztreonam (4 µg/mL) alone and in combination. Excluding false positives, 198 metabolites were identified to be affected by antibiotic treatment. Aztreonam/clavulanate combination inhibited cell wall synthesis more aggressively at 1 h and 24 h than aztreonam alone. The purine and pyrimidine metabolism, the central carbon metabolism, and the amino acid metabolism were also disrupted resulting in a prolonged bactericidal effect. This study reveals the synergistic killing mechanism of clavulanate and aztreonam combination against E. coli harboring NDM and provides a theoretical basis for the combined use of aztreonam/clavulanate in the treatment of multidrug-resistant E. coli infection.IMPORTANCEMultidrug-resistant Escherichia coli is a major threat to the health care system and is associated with poor outcomes in infected patients. The combined use of antibiotics has become an important treatment method for multidrug-resistant bacteria. However, the mechanism for their synergism has yet to be explored.

The treatment of Pseudomonas aeruginosa infection often involves the combined use of β-lactam and aminoglycoside antibiotics. In this study, we employed metabolomic analysis to investigate the mechanism responsible for the synergistic activities of meropenem/amikacin combination therapy against multidrug-resistant P. aeruginosa strains harboring OXA-50 and PAO genes. Antibiotic concentrations for meropenem (2 mg/L) monotherapy, amikacin (16 mg/L) monotherapy, and meropenem/amikacin (2/16 mg/L) combination therapy were selected based on clinical breakpoint considerations. Metabolomic analysis revealed significant alterations in relevant metabolites involved in bacterial cell membrane and cell wall synthesis within 15 min of combined drug administration. These alterations encompassed various metabolic pathways, including fatty acid metabolism, peptidoglycan synthesis, and lipopolysaccharide metabolism. Furthermore, at 1 h and 4 h, the combination therapy exhibited significant interference with amino acid metabolism, nucleotide metabolism, and central carbon metabolism pathways, including the tricarboxylic acid cycle and pentose phosphate pathway. In contrast, the substances affected by single drug administration at 1 h and 4 h demonstrated a noticeable reduction. Meropenem/amikacin combination resulted in notable perturbations of metabolic pathways essential for survival of P. aeruginosa, whereas monotherapies had comparatively diminished impacts.

Abstract An engineered bladder construct that mimics the structural and functional characteristics of native bladder is a promising therapeutic option for bladder substitution. We previously showed that pedicled vascularized smooth muscle tissue fabricated by grafting smooth muscle cell (SMC) sheets onto an axial capsule vascular bed had the potential for reliable bladder reconstruction. In this study, we investigated the feasibility of buccal mucosa graft (BMG) integration with the pedicled vascularized smooth muscle tissue to generate a full‐layer pedicled vascularized bladder construct. BMG transplanted onto vascularized smooth muscle tissue showed good survival and developed into a pedicled vascularized bladder construct with full‐layer structures, appropriate thickness, abundant vascularization, and effective barrier function. Then the full‐thickness bladder defects were, respectively, reconstructed by pedicled capsule tissue (pedicled capsule group), nonpedicled vascularized bladder construct (nonpedicled construct group), and pedicled vascularized bladder construct (pedicled construct group). The picrosirius red (PSR) staining and immunohistochemistry results showed minimal fibrosis, maximal smooth muscle proportion, and high vascular density in the pedicled construct group. A continuous mucosal layer was observed only in the pedicled construct group. Moreover, morphological and functional studies revealed better bladder compliance and good ductility in the pedicled construct group. Overall, these results suggested that the BMG could be well integrated with vascularized smooth muscle tissue and generated a pedicled, fully vascularized, and structurally organized bladder construct, which facilitated structural remodeling and functional recovery and could become an alternative to bladder reconstruction.

IntroductionThe emergence of multidrug-resistant (MDR) Acinetobacter baumannii prompts clinicians to consider treating these infections with polymyxin combination.MethodsMetabolomic analysis was applied to investigate the synergistic effects of polymyxin-B, amikacin and sulbactam combination therapy against MDR A. baumannii harboring OXA-23 and other drug resistant genes. The drug concentrations tested were based on their clinical breakpoints: polymyxin-B (2 mg/L), amikacin (16 mg/L), polymyxin-B/amikacin (2/16 mg/L), and polymyxin-B/amikacin/sulbactam (2/16/4 mg/L).ResultsThe triple antibiotic combination significantly disrupted levels of metabolites involved in cell outer membrane structure including fatty acids, glycerophospholipids, nucleotides, amino acids and peptides as early as 15 min after administration. Amikacin and polymyxin-B alone perturbed a large number of metabolites at 15 min and 1 h, respectively, but the changes in metabolites were short-lived lasting for less than 4 h. In contrast, the combination treatment disrupted a large amount of metabolites beyond 4 h. Compared to the double-combination, the addition of sulbactam to polymyxin-B/amikacin combination produce a greater disorder in A. baumannii metabolome that further confer susceptibility of bacteria to the antibiotics.ConclusionThe metabolomic analysis identified mechanisms responsible for the synergistic activities of polymyxin-B/amikacin/sulbactam against MDR A. baumannii.

Background: Apalutamide is a new drug class, which is approved to treat prostate cancer (PCa). The aim of our study was to assess the safety profiles of apalutamide in real-world through data mining of the United States Food and Drug Administration Adverse Event Reporting System (FAERS).Method: We included adverse event (AE) reports regarding apalutamide submitted to the FAERS from 2018 quarter 1 (2018Q1) to 2022 quarter 1 (2022Q1). Disproportionality analyses, including reporting odds ratio (ROR), were performed to identify the signals of AEs in patients receiving apalutamide. A signal was detected if the lower limit of the 95% confidence interval (CI) of ROR >1 and at least 3 AEs were reported.Results: The FAERS database documented 4,156 reports regarding apalutamide from 1 January 2018, to 31 March 2022. A total of 100 significant disproportionality preferred terms (PTs) were retained. Frequently observed AEs in patients receiving apalutamide included rash, fatigue, diarrhea, hot flush, fall, weight decreased, hypertension. The most significant system organ class (SOC) was “skin and subcutaneous tissue disorders”, which mainly consisted of dermatological adverse events (dAEs). The additional AEs observed with the significantly signal contain lichenoid keratosis, increased eosinophil count, bacterial pneumonia, pulmonary tuberculosis, hydronephrosis.Conclusion: Our findings provide valuable evidence for apalutamide safety profile in the real-world, which could help clinicians and pharmacists to enhance their vigilance and improve the safety of apalutamide in clinical practice.

Hypsizygus marmoreus has become one of the most popular edible mushrooms due to its high nutritional and economic value. Previous researchers found that Serratia odorifera could promote the growth of H. marmoreus by producing and secreting some of its inducers. However, the specific mechanism of action was still unclear. In this study, we found that the exogenous addition of sterile fermentation filtrate (HZSO-1), quorum sensing (QS) signaling molecules, 3-oxo-C6-HSL, cyclo(Pro-Leu), and cyclo(Tyr-Leu) could significantly promote the growth of H. marmoreus, increase the number of clamp junctions, and the diameter of mycelium (p < 0.05). In addition, non-targeted metabolomic analysis revealed that 706 metabolites were detected in the treated group. Of these, 307 metabolites were significantly different (p < 0.05). Compared with the control, 54 and 86 metabolites were significantly increased and decreased in the HZSO-1 group, respectively (p < 0.05). We speculate that the sterile fermentation filtrate of S. odorifera could mediate the carbohydrate and amino acid metabolism of H. marmoreus by influencing the pentose phosphate pathway (PPP) to increase the energy supply for the growth and development of the mycelium. The above results will further reveal the growth-promoting mechanism of S. odorifera on H. marmoreus.

The objective of this study was to evaluate whether combinations of sulbactam, meropenem, and polymyxin-B could reduce or close the gap of mutant selection window (MSW) of individual antibiotics against Acinetobacter baumannii harboring OXA-23. MICs of three antimicrobials used alone and in combination (meropenem/polymyxin-B or meropenem/polymyxin-B/sulbactam) were obtained in 11 clinical isolates and mutant prevention concentrations were determined in 4 of the 11 isolates. All isolates were resistant to meropenem or polymyxin-B. Combining meropenem and polymyxin-B with or without sulbactam resulted in synergistic bactericidal activities. Pharmacokinetic (PK) simulations of drug concentrations in the blood and epithelial lining fluid coupled with pharmacodynamic (PD) evaluations revealed that the fractions of time over the 24-h in terms of free drug concentration within the MSW (fTMSW) and above the MPC (fT>MPC) were optimized by combination therapy. The resultant clinical regimens of meropenem, polymyxin-B, and sulbactam evaluated in the PK-PD analysis were 2 g q8h, 2.5 mg/kg loading dose followed by 1.5 mg/kg q12h, and 3 g q8h, respectively, in patients with normal renal function. Subsequent corresponding equivalent exposure regimens would depend on the extent of renal failure. The overall results indicate that combination antibiotics consisting of sulbactam/meropenem/polymyxin-B can confer potential efficacy against A. baumannii harboring OXA-23, and reduce the opportunity for bacteria to develop further resistance. This study provides a framework for pharmacodynamic evaluation of drug-resistant mutant suppression in an antimicrobial co-administration setting. The results thereby lay the groundwork for additional studies and future clinical confirmation is warranted.

Amikacin and polymyxins as monotherapies are ineffective against multidrug-resistant Acinetobacter baumannii at the clinical dose. When polymyxins, aminoglycosides, and sulbactam are co-administered, the combinations exhibit in vitro synergistic activities. The minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) were determined in 11 and 5 clinical resistant isolates of A. baumannii harboring OXA-23, respectively, in order to derive the fraction of time over the 24-h wherein the free drug concentration was within the mutant selection window (fTMSW) and the fraction of time that the free drug concentration was above the MPC (fT>MPC) from simulated pharmacokinetic profiles. The combination of these three antibiotics can confer susceptibility in multi-drug resistant A. baumannii and reduce the opportunity for bacteria to develop further resistance. Clinical intravenous dosing regimens of amikacin, polymyxin-B, and sulbactam were predicted to optimize fTMSW and fT>MPC from drug exposures in the blood. Mean fT>MPC were ≥ 60% and ≥ 80% for amikacin and polymyxin-B, whereas mean fTMSW was reduced to

In this paper, kaolin was used to synthesise the europium-doped sodalite phosphors (Na8(AlSiO4)6(Cl)2:Eu3+) through the hydrothermal method and then roasting processes. The influence of anion type and concentration, sodium hydroxide concentration, Eu concentration, the roasting temperature and time on the synthesized samples were investigated. Scanning electron microscopy, X-ray diffraction and photoluminescence spectroscopy were applied to detect the crystallization, morphology and luminescence intensity of obtained sodalite and phosphors. The sodalite Na8(AlSiO4)6(Cl)2 synthesized with 10 mol/L NaOH, 2.3:5 M ratios of metakaolinite:NaCl has good crystallinity and uniform particle size, when the roasting temperature and time was 850 ℃ and 2 h, the roasted samples has product has the best crystallinity and morphology. The Na8(AlSiO4)6(Cl)2:Eu3+ powder obtained with 7 % Eu concentrations had the optimal emission intensity. The photoluminescence properties results revealed that the obtained Na8(AlSiO4)6(Cl)2:Eu3+ phosphors can be excited by 396 nm near-ultraviolet light and emits red light, suggesting promising application in LED lamps matching the excitation of the ultraviolet chip.

Empirical therapies using polymyxins combined with other antibiotics are recommended in the treatment of Acinetobacter baumannii infections. In the present study, the synergistic activities of polymyxin-B, meropenem, and sulbactam as combination therapy were investigated using metabolomic analysis. The metabolome of A. baumannii was investigated after treatment with polymyxin-B alone (2 mg/l), meropenem (2 mg/l) alone, combination of polymyxin-B/meropenem at their clinical breakpoints, and triple-antibiotic combination of polymyxin-B/meropenem and 4 mg/l sulbactam. The triple-antibiotic combination significantly changed the metabolite levels involved in cell outer membrane and cell wall biosynthesis, including fatty acid, glycerophospholipid, lipopolysaccharide, peptidoglycan, and nucleotide within 15 min of administration. In contrast, significant changes in metabolome were observed after 1 h in sample treated with either meropenem or polymyxin-B alone. After 1 h of administration, the double and triple combination therapies significantly disrupted nucleotide and amino acid biosynthesis pathways as well as the central carbon metabolism, including pentose phosphate and glycolysis/gluconeogenesis pathways, and tricarboxylic acid cycle. The addition of sulbactam to polymyxin-B and meropenem combination appeared to be an early disruptor of A. baumannii metabolome, which paves the way for further antibiotic penetration into bacteria cells. Combination antibiotics consisting of sulbactam/meropenem/polymyxin-B can effectively confer susceptibility to A. baumannii harboring OXA-23 and other drug resistant genes. Metabolomic profiling reveals underlying mechanisms of synergistic effects of polymyxin-B combined with meropenem and sulbactam against multi-drug resistant A. baumannii.

Abstract Background and Aims Exploring the mechanism influencing the choice of hospital among patients is important to render better care to them. The main purpose of this study is to evaluate the relationship between outpatients’ different internal factors (sociodemographic and psychological characteristics) and different external factors (provider characteristics) regarding their choice of hospital. Methods The data obtained via questionnaire was analyzed with a linear regression model to verify the relationship between outpatients’ internal and external factors. In addition, for external factors, we built a score reflecting a comprehensive hospital's “hard power” (diagnosis and treatment technology and expertise, i.e., to say, the curative capability) and “soft power” (whether the environment for seeing a doctor is convenient and cheap, etc.) factors which influence the choice of outpatients, and the factors were given different points and weighted according to the option's order of the questionnaire. Results We did not see evidence that internal factors such as gender, age, birthplace, and having or not having medical insurance had an effect on the comprehensive external factors of the hospital's choice (p > 0.05). However, statistically significant differences were found (p

PurposeThe purpose of this study was to perform the translation and adaption of the Cognitive Reserve Index questionnaire into Chinese and assess the reliability of the Chinese version.Materials and MethodsThe Chinese version of the Cognitive Reserve Index questionnaire was created from a standard forward-backward translation. A total of 371 volunteers, aged between 20 and 89 years, participated in this survey. Participants were divided into three age-groups (Young, Middle-aged, and Elderly), and subgroup differences were examined by independent samples t-tests, ANOVA analysis as well as post-hoc analysis. Pearson correlation analysis was applied to test the association between the total scores and each subscore (CRI-Education, CRI-WorkingActivity, and CRI-LeisureTime). The internal consistency and test-retest reliability of the Cognitive Reserve Index questionnaire were assessed. The test-retest reliability was measured among 40 participants with a 2-week interval using intraclass correlation coefficient.ResultsStrong correlations were observed between the total scores and each subscore (CRI-Education, CRI-WorkingActivity, and CRI-LeisureTime: r = 0.65, 0.79, and 0.70, respectively). In contrast, it was found low to moderate correlations among three subscores. The internal consistency was acceptable (Cronbach's alpha coefficient = 0.68). The intraclass correlation coefficient for total scores of the Chinese version of the Cognitive Reserve Index questionnaire was 0.87 (95% CI 0.74–0.93).ConclusionThe Chinese version of the Cognitive Reserve Index questionnaire was a potentially reliable and practical tool for evaluating cognitive reserve accumulated through a person's life span.

Abstract The emergence of polymyxin resistance in Gram-negative bacteria infections has motivated the use of combination therapy. This study determined the mutant selection window (MSW) of polymyxin B alone and in combination with meropenem and fosfomycin against A. baumannii strains belonging to clonal lineages I and III. To evaluate the inhibition of in vitro drug resistance, we investigate the MSW-derived pharmacodynamic indices associated with resistance to polymyxin B administrated regimens as monotherapy and combination therapy, such as the percentage of each dosage interval that free plasma concentration was within the MSW (%TMSW) and the percentage of each dosage interval that free plasma concentration exceeded the mutant prevention concentration (%T>MPC). The MSW of polymyxin B varied between 1 and 16 µg/mL for polymyxin B-susceptible strains. The triple combination of polymyxin B with meropenem and fosfomycin inhibited the polymyxin B-resistant subpopulation in meropenem-resistant isolates and polymyxin B plus meropenem as a double combination sufficiently inhibited meropenem-intermediate, and susceptible strains. T>MPC 90% was reached for polymyxin B in these combinations, while %TMSW was 0 against all strains. TMSW for meropenem and fosfomycin were also reduced. Effective antimicrobial combinations significantly reduced MSW. The MSW-derived pharmacodynamic indices can be used for the selection of effective combination regimen to combat the polymyxin B-resistant strain.

ObjectiveTo prepare technetium-99m (99mTc)-labeled pH (low) insertion peptide variant 7 [pHLIP (Var7)] and carry out small-animal single-photon-emission computed tomography (SPECT)/computed tomography (CT) imaging of tumor-bearing nude mice in vivo to study its value in the early diagnosis of triple-negative breast cancer (TNBC).MethodsThe pHLIP (Var7) sequence was synthesized via solid-phase peptide synthesis. Four amino acids, Gly-(D)-Ala-Gly-Gly, were attached to the N-terminus of pHLIP (Var7) to form a strong chelating group containing an N4 structure. The peptide was labeled with 99mTc using a direct labeling method. We determined the in vitro binding fraction of 99mTc-pHLIP (Var7) to MDA-MB-231 cells. Serial biodistribution studies and small-animal SPECT/CT imaging in MDA-MB-231 TNBC-bearing mice were performed using 99mTc-pHLIP (Var7).ResultsThe radiochemical yield and purity of 99mTc-pHLIP (Var7) were 99.49 ± 0.17% and 99.63 ± 0.44%, respectively. The radiochemical purity was still more than 96% after 24 h in serum. The binding fraction of 99mTc-pHLIP (Var7) to MDA-MB-231 cells continuously increased in an acidic environment and was significantly higher than the cell-binding fraction (P < 0.01) at pH = 7.4 and the cell-binding fraction (P < 0.01) of 99mTc-kVar7 at different pH values (pH = 6.0, 6.5, 7.0 and 7.4) at each time point (P < 0.01). The distribution of 99mTc-pHLIP (Var7) in tumors at each time point was significantly greater than that of 99mTc-kVar7 (P < 0.01). SPECT/CT imaging was largely consistent with the biodistribution results; the tumor was clearly imaged at each time point after injection of 99mTc-pHLIP (Var7) but could not be imaged after injection of 99mTc-kVar7.Conclusion99mTc-pHLIP (Var7) showed a high radiochemical yield and stability and was highly concentrated in tumor tissues. Although there was strong radioactive background in the abdomen of tumor-bearing nude mice, it did not hinder early diagnosis of TNBC.

In this paper, stoneware was prepared using steel slag shale as the main raw material. A typical ceramic sintering procedure was used to evaluate the effects of a sintering temperature of 1050∼1130 °C on the linear shrinkage, water absorption, bulk density, and flexural strength parameters of stoneware samples. The stoneware samples were characterized by XRF, XRD, and SEM. The results showed that the performance of the steel slag content of 40% at sintering temperature of 1110 °C was better than the other samples. The main phases of the sample are composed of the quartz phase, the pyroxene phase, and the anorthite phase. Among them, the water absorption rate is 1.36%, the linear shrinkage rate is 11.36%, the bulk density is 2.46 g cm ^−3 , and the flexural strength is 71.13 Mpa. Anorthite and pyroxene improve the bending strength of stoneware samples, which is realized by the prestress mechanism.

Pleurotus eryngii is a commercially important edible fungus with high nutritional and economic value. However, few functional studies have examined key genes affecting the growth and development of P. eryngii. In this study, transformed strains, including over-expression (PeGNAI-OE) and RNA interference (PeGNAI-RNAi) lines, were constructed to elucidate the role of GNAI in P. eryngii growth. GNAI expression was found to affect the mycelial growth and the number of clamp connections. Moreover, the transformed strains were shown to have higher endogenous cAMP levels, thus affecting amylase and laccase activity. Fruiting experiments showed that GNAI expression revealed the formation of P. eryngii primordia and the number of buttons, while transcription analysis identified GNAI gene involvement in the growth and development of P. eryngii. Seven downstream genes regulated by GNAI were differentially expressed in PeGNAI-OE and PeGNAI-RNAi compared to wild type (WT). These genes may be related to mycelial growth and enzyme activity. They were involved in the MAPK signaling pathway, inositol phosphate metabolism, ascorbate, aldarate metabolism, and starch and sucrose metabolism. In summary, GNAI performs different physiological functions in regulating the growth and development of P. eryngii. Importantly, the molecular mechanisms of GNAI regulatory function are relatively complex and need further study.

This study aimed to examine specific niches and usage for the aztreonam/amoxicillin/clavulanate combination and to use population pharmacokinetic simulations of clinical dosing regimens to predict the impact of this combination on restricting mutant selection. The in vitro susceptibility of 19 New-Delhi metallo-β-lactamase (NDM)-producing clinical isolates to amoxicillin/clavulanate and aztreonam alone and in co-administration was determined based on the minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC). The fractions of a 24-h duration that the free drug concentration was within the mutant selection window (fTMSW) and above the MPC (fT>MPC) in both plasma and epithelial lining fluid were determined from simulations of 10,000 subject profiles based on regimens by renal function categories. This combination reduced the MIC of aztreonam and amoxicillin/clavulanate to values below their clinical breakpoint in 7/9 K. pneumoniae and 8/9 E. coli, depending on the β-lactamase genes detected in the isolate. In the majority of the tested isolates, the combination resulted in fT>MPC > 90% and fTMSW < 10% for both aztreonam and amoxicillin/clavulanate. Clinical dosing regimens of aztreonam and amoxicillin/clavulanate were sufficient to provide mutant restriction coverage for MPC and MIC ≤ 4 mg/L. This combination has limited coverage against NDM- and extended-spectrum β-lactamase co-producing E. coli and K. pneumoniae and is not effective against isolates carrying plasmid-mediated AmpC and KPC-2. This study offers a potential scope and limitations as to where the aztreonam/amoxicillin/clavulanate combination may succeed or fail.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in most parts of the world. Although there is no first-line drug approved for the treatment of NAFLD, polyene phosphatidylcholine (PPC) is used by clinicians to treat NAFLD patients. This study aimed to evaluate the efficacy of PPC on a mice model of NAFLD, and to study the PPC’s mechanism of action. The mice were fed a choline-deficient, L-amino acid-defined (CDAA) diet to induce NAFLD and were subsequently treated with PPC. The treatment effects were evaluated by the liver index, histopathological examination, and routine blood chemistry analyses. Lipidomics and metabolomics analyses of 54 samples were carried out using ultraperformance liquid chromatography (UPLC) coupled to a mass spectrometer to select for changes in metabolites associated with CDAA diet-induced NAFLD and the effects of PPC treatment. The intestinal flora of mice were extracted for gene sequencing to find differences before and after the induction of NAFLD and PPC treatment. PPC significantly improved the CDAA diet-induced NAFLD condition in mice. A total of 19 metabolites including 5 polar metabolites and 14 lipids showed marked changes. In addition, significant differences in the abundance of Lactobacillus were associated with NAFLD. We inferred that the protective therapeutic effect of PPC on the liver was related to the supplement of phosphatidylcholine, lysophosphatidylcholine, and sphingomyelin (PC, LPC, and SM, resectively) and acylcarnitine metabolism. This study developed a methodology for exploring the pathogenesis of NAFLD and can be extended to other therapeutic agents for treating NAFLD.

BackgroundChina established the Tiered-network Healthcare Delivery System (THDS) in 2015 to address the disproportionate number of patients attending tertiary hospitals relative to primary- or secondary-care institutions. Although the reported number of outpatients visiting tertiary hospitals is slowly decreasing, numerous patients choose to visit them regardless of their disease's severity. To effectively implement the THDS, this article explored the relationship between patients' sociodemographic and belief characteristics and their healthcare-seeking behavioral decision-making in China.MethodsData obtained through questionnaires were analyzed using decision tree and logistic regression models to explore outpatients' characteristics and medical decision-making using comprehensive feature data. Moreover, further statistical analyses were conducted on the outpatient data obtained from the regional population health platform in Jiaxing, China.ResultsThe decision tree model revealed that whether outpatients have medical insurance is the primary factor guiding their healthcare-seeking behaviors, with those without medical insurance more likely to choose primary or secondary hospitals to treat minor diseases. For those with medical insurance, profession is the main factor, with industrial workers more inclined to choose primary or secondary hospitals for minor diseases. The logistic regression analyses revealed that outpatients without insurance and who were not freelancers or individual owners were more likely to choose primary or secondary hospitals for minor diseases. Further statistical analysis of the data from the Jiaxing population health platform showed that, for minor or general diseases, outpatients without medical insurance and employed as farmers tended to choose primary and secondary hospitals over tertiary hospitals.ConclusionThe three analyses yielded consistent results: in China, medical insurance and patients' profession are the most important factors guiding outpatients' healthcare-seeking behaviors. Accordingly, we propose that the government should focus on economic reforms to increase outpatients' visits to primary and secondary hospitals and diagnosis-related groups' payment of medical insurance to decrease the admittance of patients with minor diseases in large tertiary hospitals. Meanwhile, the government should correct patients' belief prejudice about selecting hospitals through corresponding publicity.

Background To develop a model of malignant risk prediction of solitary pulmonary nodules (SPNs) using metabolic characteristics of lesions. Methods A total of 362 patients who underwent PET/CT imaging from January 2013 to July 2017 were analyzed. Differences in the clinical and imaging characteristics were analyzed between patients with benign SPNs and those with malignant SPNs. Risk factors were screened by multivariate nonconditional logistic regression analysis. The self‐verification of the model was performed by receiver operating characteristic (ROC) curve analysis, and out‐of‐group verification was performed by k‐fold cross‐validation. Results There were statistically significant differences in age, maximum standardized uptake value (SUVmax), size, lobulation, spiculation, pleural traction, vessel connection, calcification, presence of vacuoles, and emphysema between patients with benign nodules and those with malignant nodules (all P

Permeable pavement is part of the low impact development (LID) measurement, which can decrease urban surface runoff coefficient and flood peak flow. In this paper, a two-way, six-lane road in Nanjing was selected as the study area. Storm water management model (SWMM) was used to simulate the effect of different pavement structures (drainage surface, permeable pavement and permeable road) under different rainfall conditions on reducing surface runoff and controlling urban stormwater. The simulation results show that the drainage surface can reduce part of surface runoff, but it has no influence on the reduction and hysteresis of flood peak. The permeable pavement can reduce part of surface runoff and flood peak and can delay peak time. The permeable road has better effect on reducing runoff coefficient and flood peak, which can effectively reduce the pressure of urban drainage and reduce the risk of stormwater flood. Keywords: SWMM, Drainage surface, Permeable pavement, Ratio of flood peak reduction, Runoff coefficient

Background: Enhancer RNAs (eRNAs) are a group of lncRNAs transcribed from enhancers, whose regulatory effects on gene expression are an emerging area of interest. However, the role of eRNAs in regulating trophoblast cells and unexplained recurrent pregnancy loss (URPL) remains elusive. Methods: We profiled eRNAs in villi from URPL patients and matched controls by RNA-seq. Functions of URPL-related eRNAs were further investigated in vitro. Results: We identified lnc-SLC4A1-1, which was transcribed from an active enhancer marked with H3K27ac and H3K4me1 and so-called eRNA, highly expressed in URPL patients. Gain-of-function experiments indicated that lnc-SLC4A1-1 facilitated trophoblast cell migration and apoptosis. Mechanistically, as an eRNA, lnc-SLC4A1-1 was retained in the nuclei and recruited transcription factor NF-κB to bind to CXCL8, resulting in increased H3K27ac in the CXCL8 promoter and subsequent elevation of CXCL8 expression. Activation of CXCL8 exacerbated inflammatory reactions in trophoblast cells by inducing TNF-α and IL-1β, which could be blocked by an antagonist of lnc-SLC4A1-1. Interpretation: These findings indicate that an eRNA, lnc-SLC4A1-1, alters trophoblast function via activation of immune responses and by regulating the NF-κB/CXCL8 axis. Our study provides new insights in understanding lncRNA/eRNA function in pathological pregnancy, potentially informing on therapeutic strategies for URPL. Fund: National Natural Science Foundation of China, Natural Science Foundation of Jiangsu Province, National Key Research and Development Program, the Priority Academic Program for the Development of Jiangsu Higher Education Institutions. Keywords: Recurrent pregnancy loss, Enhancer RNA, Inflammation

Objective. To evaluate the diagnostic efficacy of MDA-MB-231 triple-negative breast cancer with 125I-labeled pHLIP (Var7) by single-photon emission computed tomography/computed tomography (SPECT/CT) imaging. Methods. The binding fraction of [125I]I-pHLIP (Var7) and MDA-MB-231 cells was measured at pH 7.4 and pH 6.0, and tumor-bearing mice were subjected to small-animal SPECT/CT imaging studies. Results. At pH=6.0, the binding fractions of [125I]I-pHLIP (Var7) and MDA-MB-231 cells at 10 min, 40 min, 1 h, and 2 h were 1.9±0.1%, 3.5±0.1%, 6.3±0.8%, and 6.6±0.3%, respectively. At pH=7.4, there was no measured binding between [125I]I-pHLIP (Var7) and MDA-MB-231 cells. Small-animal SPECT/CT imaging showed clearly visible tumors at 1 and 2 h after injection. Conclusions. [125I]I-pHLIP (Var7) could bind to MDA-MB-231 cells in an acidic environment, and small-animal SPECT/CT imaging showed clear tumors at 1 and 2 h after probe injection.

Under strong earthquakes, steel structures are prone to undergoing ultra-low cycle fatigue (ULCF) fracture after sustaining cyclic large-strain loading, leading to severe earthquake-induced damage. Thus, establishing a prediction method for ULCF plays a significant role in the seismic design of steel structures. However, a simple and feasible model for predicting the ULCF life of steel structures has not been recognized yet. Among existing models, the ductile fracture model based on ductility capacity consumption has the advantage of strong adaptability, while the loading history effect in the damage process can also be considered. Nevertheless, such models have too many parameters and are inconvenient for calibration and application. To this end, focusing on the prediction methods for ULCF damage in steel structures, with the fragile parts being in moderate and high stress triaxiality, this paper proposes a simplified uncoupled prediction model that considers the effect of stress triaxiality on damage and introduces a new historical-effect related variable function reducing the calibration work of model parameters. Finally, cyclic loading test results of circular notched specimens verify that the proposed model has the advantages of a small dispersion of parameters for calibration, being handy for application, and possessing reliable results, providing a prediction method for ULCF damage of structural steels.

In order to design and fabricate hydrophobic, durable and anti-icing coating for aircraft, a polyurethane elastomer matrix was hydrophobically modified and incorporated with fluorinated SiO _2 nanoparticles to prepare a micro/nanostructured coating. The micro/nanostructured coating with low surface energy displayed significantly improved mechanical properties and hydrophobicity, which exhibited the water contact angle of 162° as well as the sliding angle of 2°. The coating is highly stretchable, which could sustain large-scale extension, and exhibits tensile strength and elongation at break up to 16.22 MPa and 385%, respectively. Furthermore, the coating exhibited a remarkably weak ice adhesion strength of 14.33 kPa, on which the accumulative ice is prone to fall off under natural wind and its own weight. The coating sustained long-term superhydrophobic properties and anti-icing performance even after 1000 abrasion cycles. The proposed method for the production of scalable superhydrophobic coating is cost-effective and can be applied in aerospace and automotive anti-icing systems.

Europium-doped yttrium oxide (Y2O3:Eu3+) phosphors were successful synthesized by hydrothermal method from waste phosphors in the presence of sodium citrate. The synthesized samples were characterized by X-ray diffraction, scanning electron microscopy and photoluminescence spectroscopy. The experimental results showed that the morphology and photoluminescent properties of the obtained samples had a strong dependence on the concentrate of sodium citrate, the addition amount of NaOH and Eu in the hydrothermal process. Well-dispersed Y2O3:Eu3+ hexagonal microdisk with average diameter of 2 μm were synthesized in the presence of 6 mol% Eu, 37.5 mmol NaOH, molar ratios of Cit3−:Y3+ = 1:1. The photoluminescence properties measurement reveled that Y2O3:Eu3+ phosphors showed a strong red emission corresponding to 5D0–7F2 (613 nm), suggesting promising application in optoelectronics. Keywords: Hydrothermal synthesis, Y2O3:Eu3+, Morphology, Photoluminescence, Waste phosphors

Background: Aberrant DNA methylation is considered to be a potential cause of recurrent pregnancy loss (RPL), while potential mechanism has not yet been elucidated. Methods: In order to uncover the contribution of the perturbation of DNA methylation in RPL, we performed genome-wide DNA methylation analysis combined with genome-wide gene expression in decidua tissue. Findings: Totally, 539 differentially methylated regions (DMRs) were identified and significantly correlated with gene expressions. We observed that hypo-methylated DMR near CREB5 recruited transcription factors binding, such as P53 and SP1, and in turn upregulated CREB5. Compromised cell migration and apoptosis were observed in human CREB5 overexpression trophoblast cell lines, indicating dysfunctional trophoblast cells might contribute to RPL after hypo-methylation of CREB5. In addition, overexpression of CREB5 altered cell cycle. Interpretation: Our data highlights a role of CREB5 involved in the pathogenesis of RPL, and CREB5 maybe a potential diagnostic biomarker for RPL. Keywords: Recurrent pregnancy loss, DNA methylation, Gene expression, CREB5

The hybrid antistatic agent SCNTs/OAA composed of sulfonated carbon nanotubes (SCNTs) and organic antistatic agent (OAA) was treated on the fiber surface to construct the hybrid conductive layer. Among them, SCNTs were synthesized through a simple method, and their chemical structure and morphology were characterized. SCNTs had good dispersibility due to the presence of sulfonic acid groups, which made SCNTs uniformly dispersed on the fiber surface. The SCNTs/OAA-treated fiber was hardly affected by relative humidity, because SCNTs form a continuous and uniform physical conductive network on the fiber surface. When the addition amount of SCNTs/OAA was 0.5~2 wt%, the fiber had excellent antistatic ability. Under the synergistic effect of SCNTs and OAA, the resistivity of SCNTs/OAA-treated fiber was almost not affected by fiber stretching.

The biosynthesis of pyridine rings is still poorly understood. Here the authors propose a biosynthetic pathway for pyridine-containing rubrolones, which is characterized by a non-enzymatic condensation and cyclization of the pyridine moiety.

Bingham material has commonly been used to control subsidence damage caused by underground coal mining. This paper discusses the Bingham materials fluidity characteristics in the pipe transportation. A general description about the components of the Bingham materials is provided involving the various chemical behavior and rheological performance. The flow characteristics in pipeline has been simulated in the straight pipe and 90° elbow pipe respectively combined with the pressure loss and conveying velocity distribution. With the help of the commercial Computational Fluid Dynamic (CFD) code FLUENT, the modeling is conducted with various materials feeding velocity. These results show the local resistance loss in bending pipe is significantly higher than the resistance in the straight pipe under the same condition associated with Bingham materials transportation. The velocity distribution of the slurry solid particle in the slurry movement forward is more decentralize as the increasing hydraulic inlet velocity. Bingham materials fluidity characteristics based on different chemical behavior was concluded in the paper.

Retroperitoneal malignant schwannomas are extremely rare. Only a few cases have been reported, only one of which occurred in a child. We herein report a case of retroperitoneal malignant schwannoma in a 2-year-old boy who presented with a painless mass in the right lumbar region. The mass had gradually enlarged during a 1-year period, and it was about the size of the patient’s fist at the time of consultation. Whole-abdomen computed tomography revealed a space-occupying lesion in the retroperitoneum infiltrating from the L1 to L4 spinal canal. A preoperative diagnosis of a retroperitoneal tumor was made, and complete tumorectomy was performed. Postoperative pathological examination showed a malignant schwannoma. The tumor recurred 1 month after the first operation, and a second complete excision was carried out; the postoperative pathologic examination findings were similar to the previous findings. The patient recovered well and continued to undergo close follow-up.

Lithium-sulfur (Li-S) battery is considered one of the possible alternatives for next-generation high energy batteries. However, its practical applications are still facing great challenges because of poor electronic conductivity, large volume change, and polysulfides dissolution inducing “shuttle reaction” for the S cathode. Many strategies have been explored to alleviate the aforementioned concerns. The most common approach is to embed S into carbonaceous matrix for constructing C-S composite cathodes. Herein, we fabricate the C-S cathode reduced graphene oxide-S (rGO-S) composites via one step hydrothermal and in-situ thermal reduction methods. The structural features and electrochemical properties in Li-S cells of the two type rGO-S composites are studied systematically. The rGO-S composites prepared by one step hydrothermal method (rGO-S-HT) show relatively better comprehensive performance as compared with the ones by in-situ thermal reduction method (rGO-S-T). For instance, with a current density of 100 mA g−1, the rGO-S-HT composite cathodes possess an initial capacity of 1290 mAh g−1 and simultaneously exhibit stable cycling capability. In particular, as increasing the current density to 1.0 A g−1, the rGO-S-HT cathode retains a reversible capacity of 582 mAh g−1 even after 200 cycles. The enhanced electrochemical properties can be attributed to small S particles uniformly distributed on rGO sheets enabling to significantly improve the conductivity of S and effectively buffer large volume change during lithiation/delithiation.

Abstract Background Colloid adenocarcinoma of the lung is a rare subtype of variants of invasive adenocarcinomas. We report the appearance of this unusual entity on 18F-fluorodeoxyglucose positron emission tomography/computed tomography. Case presentation A 60-year-old man of Chinese Han nationality coughed with a little white sputum for 1 month. Chest computed tomography showed multiple bilateral subpleural nodules and plaques accompanied by air bronchograms, which were most concentrated in the lower lobe of his right lung. Positron emission tomography indicated increased radioactivity uptake with a maximum standardized uptake value of 3.5. Positron emission tomography/computed tomography showed a soft tissue density lesion in his left adrenal gland with a maximum standardized uptake value of 4.1. The positron emission tomography/computed tomography appearance suggested a primary colloid adenocarcinoma in the lower lobe of his right lung accompanied by intrapulmonary and left adrenal gland metastases. The diagnostic rate of colloid adenocarcinoma can be increased by combining the anatomic and metabolic information of lesions. Conclusions The advantage of positron emission tomography/computed tomography in the diagnosis of colloid adenocarcinoma, as with other cancers, is the ability to locate extrapulmonary disease, facilitating clinical staging.

Graphite/graphene particles were employed as functional fillers to modify hybrid polytetrafluoroethylene/polyisophthaloyl metaphenylene diamine (PTFE/Nomex) fabric-reinforced phenolic composites. The tribology behavior was investigated using a ball-on-disk wear tester, together with a 3D digital microscope. The graphite/graphene exhibits the synergetic effect from the results, which not only reduces the friction efficient but also improves the wear resistance of the composites. Moreover, the wear mechanisms were studied by the wear surface microstructure analysis. It is proposed that the synergetic effect includes mainly the positive rolling effect from the graphene and an improved load-carrying capacity brought by graphite. In addition, in order to obtain the optimized formulation to satisfy the bearing application, the influence of graphite and graphene content on the tribological property of the composites was studied in detail. On the basis of that, the application research was carried out on the bearing oscillating wear test, which will evaluate the engineering service life of the composite.

Intussusception is common in children. Double simultaneous intussusception is a peculiar variety of intussusception with only 14 previously reported cases. We report a unique case of a child who suffered from double simultaneous intussusception with two lead points (Meckel’s diverticulum and intestinal duplication). The patient was successfully treated with manual reduction along with resection of Meckel’s diverticulum and intestinal duplication. The child recovered well.

Spontaneous fetal femoral fractures are uncommon in the paediatric setting. The major clinical presentations of a spontaneous fetal femoral fracture are femoral angulation, shortness of the femur and even a marked fracture line. This case report describes a spontaneous fetal femoral fracture of the right femur, which was detected by routine ultrasonography during the 19 th week of gestation in a 24-year-old woman. On routine follow-up visits, the angulation of the right femur in the fetus gradually improved. A caesarean section was undertaken at 39 weeks +5 days of gestation and an X-ray was taken on the second day after birth, which showed that the fracture had healed and the callus had been absorbed. The lengths of the two femurs of the baby were not equal; the right femur was 84 mm, which was 11 mm shorter than the left femur. In cases like this, postnatal follow-up is essential so that an operation can be carried out in a timely manner when the deformity is apparent.

Cardiac development is a dynamic process and sensitive to environmental chemicals. Triclosan is widely used as an antibacterial agent and reported to transport across the placenta and affect embryonic development. Here, we used human embryonic stem cell- (hESC-) derived cardiomyocytes (CMs) to determine the effects of TCS exposure on cardiac development. After TCS treatment, the differentiation process was significantly blocked and spontaneous beating rates of CMs were also decreased. Transcriptome analysis showed the dysregulation of genes involved in cardiogenesis, including GATA4 and TNNT2. Additionally, DNA methylation was also altered by TCS exposure, especially in those regions with GATA motif enrichment. These alterations of transcriptome and DNA methylation were all associated with signaling pathways integral to heart development. Our findings indicate that TCS exposure might cause cardiomyocyte differentiation toxicity and provide the new insights into how environmental factors regulate DNA methylation and gene expressions during heart development.

Recent experimental results showed that the Tg of cured resin scarcely decreased and the impact strength of resins increased by over 50% when a tetrafunctional epoxy named N,N,N',N'-tetraglycidyl-4,4'-diaminodiphenyl ether (TGDDE) was introduced to an appropriate flexible chain from a dimer fatty acid (DFA). In order to understand the reason for this phenomenon, the modification and the chemical structure of the prepolymer together with the curing reaction and the viscoelasticity of the cured resins were studied in detail in the present work. The results indicated that the modification would help the prepolymer improve its molecular mobility. As a result, the resins could be further cured, resulting in the cross-linking density increasing. This is because the curing efficiency was increased, but the tetrafunctional epoxy was not cured completely due to its large steric hindrance. Moreover, the flexibility of some parts of the networks was improved, which was beneficial for the toughness of the cured resins. Therefore, the toughness of the tetrafunctional resin was improved with little influence on the thermal properties when the epoxies were modified with an appropriate content of DFA.