Crosstalk between Endothelial Cells and Tumor Cells: A New Era in Prostate Cancer Progression.

Prostate cancer stands as one of the most prevalent malignancies afflicting men worldwide. The tumor microenvironment plays a pivotal role in tumor progression, comprising various cell types including endothelial cells, tumor-associated fibroblasts, and macrophages. Recent accumulating evidence underscores the indispensable contribution of endothelial cells to prostate cancer development. Both endothelial cells and tumor cells release a multitude of factors that instigate angiogenesis, metastasis, and even drug resistance in prostate cancer. These factors serve as regulators within the tumor microenvironment and represent potential therapeutic targets for managing prostate cancer. In this review, we provide an overview of the crucial functions of endothelial cells in angiogenesis, metastasis, and drug resistance, and their prospective therapeutic applications in combating this disease.

Coexistent, Competing Tunnelling, and Hopping Charge Transport in Compressed Metal Nanocluster Crystals.

Understanding charge transport among metal particles with sizes of approximately 1 nm poses a great challenge due to the ultrasmall nanosize, yet it holds great significance in the development of innovative materials as substitutes for traditional semiconductors, which are insulative and unstable in less than ∼10 nm thickness. Herein, atomically precise gold nanoclusters with well-defined compositions and structures were investigated to establish a mathematical relation between conductivity and interparticle distance. This was accomplished using high-pressure in situ resistance characterizations, synchrotron X-ray diffraction (XRD), and the Murnaghan equation of state. Based on this precise correlation, it was predicted that the conductivity of Au25(SNap)18 (SNap: 1-naphthalenethiolate) solid is comparable to that of bulk silver when the interparticle distance is reduced to approximately 3.6 Å. Furthermore, the study revealed the coexisting, competing tunneling, and incoherent hopping charge transport mechanisms, which differed from those previously reported. The introduction of conjugation-structured ligands, tuning of the structures of metal nanoclusters, and use of high-pressure techniques contributed to enhanced conductivity, and thus, the charge carrier types were determined using Hall measurements. Overall, this study provides valuable insight into the charge transport in gold nanocluster solids and represents an important advancement in metal nanocluster semiconductor research.

Efficacy and safety of anti-PD-1 monotherapy versus anti-PD-1 antibodies plus lenvatinib in patients with advanced hepatocellular carcinoma: a real-world experience.

Background: The efficacy of anti-programmed cell death (PD)-1 monotherapy in advanced hepatocellular carcinoma (aHCC) is limited, and combination therapy with lenvatinib and pembrolizumab has shown promising results. However, comparative studies between immune monotherapies and combination therapies are lacking. Objectives: To investigate the efficacy and safety of anti-PD-1 monotherapy (PD-1) and anti-PD-1 plus lenvatinib (PD-1 + L) in patients with aHCC to guide clinical treatment decisions. Design: A retrospective study was conducted on a cohort of patients with aHCC who received either PD-1 monotherapy or PD-1 + L combination therapy between January 2018 and January 2020. Methods: The study retrospectively reviewed the medical records of 94 eligible patients with aHCC, with 39 in the PD-1 group and 55 in the PD-1 + L group. The efficacy outcomes, including objective response rate (ORR), disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety, were assessed. Results: With a median follow-up of 30.1 months, the PD-1 + L group demonstrated a significantly higher ORR (32.7% versus 10.3%, p = 0.013), better DCR (80.0% versus 53.8%, p = 0.012), longer median PFS (10.6 versus 4.4 months, p < 0.001) and longer median OS (18.4 versus 8.5 months, p = 0.013) than PD-1 group. For the responders, the efficacy of the two groups was durable (DOR was 11.6 versus 3.5 months, p = 0.009). Subgroup analyses based on prior tyrosine kinase inhibitor (TKI) treatment and the presence or absence of macrovascular tumor thrombosis or extrahepatic metastases favored the PD-1 + L group. The combination therapy was a good predictor of PFS and OS in multivariate analysis. Grade 3/4 treatment-related adverse events were more common in PD-1 + L group, with higher incidences of hypertension and hand-foot skin reactions. Conclusions: PD-1 monotherapy and PD-1 plus lenvatinib combination therapy were well-tolerated in patients with aHCC. PD-1 + L showed significantly better survival benefits than PD-1 monotherapy.

Understanding the impact of PD-1 and lenvatinib combination therapy on advanced hepatocellular carcinoma Abstract: This plain language summary provides a description of our research on the combination therapy of PD-1 and lenvatinib for advanced Hepatocellular carcinoma (aHCC). We aimed to investigate the effectiveness and safety of this treatment approach and offer insights for clinical decisions. Why was this study done? HCC is a challenging condition to treat, especially in advanced stages. We explored whether the combination of two drugs, PD-1 and lenvatinib, can offer better outcomes for patients with aHCC than PD-1 monotherapy. What did the researchers do? We conducted a retrospective study on patients diagnosed with aHCC who received PD-1 alone or PD-1 combined with lenvatinib between January 2018 and January 2020. We analysed the medical records to assess the treatment's efficacy and safety. What did the researchers find? After a median follow-up of 30.1 months, we observed significant improvements in the combination therapy group, with higher response rates, better disease control, longer progression free survival, and more extended overall survival than those in the PD-1 monotherapy group. Responders in the combination group also experienced a longer duration of response. What do the findings mean? Our results address the lack of data for real-world clinical experiences regarding anti-PD-1 monotherapy for patients with aHCC compared to immunotherapy plus lenvatinib are lacking. The combination of PD-1 and lenvatinib was more effective and offered better survival benefits for patients with aHCC than PD-1 alone. These results could provide new hope for patients with this challenging condition. Limitations: The study was conducted at a single centre with relatively few patients. Additionally, most patients had hepatitis B-associated liver cancer, which may limit the generalisability of our findings to other populations. Conclusions: PD-1 plus lenvatinib is a promising treatment option for patients with aHCC. It is well-tolerated, and its effectiveness surpasses that of PD-1 therapy alone. Our findings could potentially guide clinicians in making treatment decisions for patients with aHCC.

High-Impact Performance and Thermal Properties of Polyimine Nanocomposites Reinforced by Silicon Carbide Nano-Whiskers.

Polymer nanocomposites, which combine the advantages of polymers and fillers, are widely used in the field of automobile and aviation. Polyimine (PI) is an emerging thermoset material with remarkable properties, such as malleability, recyclability, and self-healing. Silicon carbide nano-whiskers (SiCw), as a cheap and high-hardness filler material, are chosen to enhance the properties of polyimine matrix. Silicon carbide nano-whisker-reinforced polyimine (PI-SiCw) nanocomposites were successfully fabricated by heat pressing, which was confirmed by FTIR and XPS tests. According to the results of mechanical tests, the mechanical properties of PI-SiCw nanocomposites were obviously improved. For example, with the addition of 0.5% SiCw, bending strength and bending elongation at break can be simultaneously increased by 33% and 148%, respectively. Surprisingly, the impact strength of PI-SiCw nanocomposites with 2% SiCw was increased by 154% compared to the matrix. SEM and EDS tests showed that the evenly distributed SiCw in the polyimine matrix enhanced the mechanical properties of PI-SiCw nanocomposites according to the mechanism of whiskers pulling out and the bridging principle. According to the TGA test results, the PI composites with SiCw retain a higher weight percentage at 800 °C. The reason was the combined effect of the good thermal stability of SiCw and their strong interactions with the PI matrix. As a result, introducing SiCw into the PI matrix imparts a slight improvement in thermal stability. This article presents an avenue of cost-effective research to enhance the mechanical properties of polyimine composites.

Polymethoxyflavone-Enriched Fraction from Ougan (Citrus reticulata cv. Suavissima) Attenuated Diabetes and Modulated Gut Microbiota in Diabetic KK-Ay Mice.

Diabetes mellitus is a serious, chronic disease worldwide; yet it is largely preventable through physical activity and healthy diets. Ougan (Citrus reticulata cv. Suavissima) is a characteristic citrus variety rich in polymethoxyflavones. In the present study, the anti-diabetic effects of the polymethoxyflavone-enriched fraction from Ougan (OG-PMFs) were investigated. Diabetic KK-Ay mice were supplemented with different doses of OG-PMFs for 5 weeks. Our results demonstrated that OG-PMFs exhibited robust protective effects against diabetes symptoms in KK-Ay mice. The potential mechanisms may partially be attributed to the restoration of hepatic GLUT2 and catalase expression. Notably, OG-PMF administration significantly altered the gut microbiota composition in diabetic KK-Ay, indicated by the suppression of metabolic disease-associated genera Desulfovibrio, Lachnoclostridium, Enterorhabdus, and Ralstonia, implying that the gut microbiota might be another target for OG-PMFs to show effects. Taken together, our results provided a supplementation for the metabolic-protective effects of PMFs and highlighted that OG-PMFs hold great potential to be developed as a functional food ingredient.

Common and Distinct Neural Patterns of Attention-Deficit/Hyperactivity Disorder and Borderline Personality Disorder: A Multimodal Functional and Structural Meta-analysis.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) and borderline personality disorder (BPD) have partially overlapping symptom profiles and are highly comorbid in adults. However, whether the behavioral similarities correspond to shared neurobiological substrates is not known. METHODS: An overlapping meta-analysis of 58 ADHD and 66 BPD whole-brain articles incorporating observations from 3401 adult patients and 3238 healthy participants was performed by seed-based d mapping. Brain maps were subjected to meta-analytic connectivity modeling and data-driven functional decoding analyses to identify associated neural circuit alterations and relations to behavioral dimensions. RESULTS: Both groups exhibited hypoactivated abnormalities in the left inferior parietal lobule, and altered clusters of the bilateral superior temporal gyrus were disjunctive in ADHD and BPD. No overlapping structural abnormalities were found. Multimodal alterations of ADHD were located in the right putamen and of BPD in the left orbitofrontal cortex. CONCLUSIONS: The transdiagnostic neural bases of ADHD and BPD in temporoparietal circuitry may underlie overlapping problems of behavioral control, while disorder-specific substrates in frontostriatal circuitry may account for their distinguishing features in motor and emotion domains, respectively.

Mechanical and Recyclable Properties of Polyimine Enhanced by Biomimetic Modification of Graphene Oxide Sheets/Silicon Carbide Nano-Whiskers.

Inspired by the mineral bridge between hard phase layers of natural nacre, the biomimetic modified silicon carbide nano-whiskers (MSiCw)/graphene oxide sheets (MGO) reinforced polyimine (PI) composites (MSiCw-MGO-PI) were successfully prepared by heat-pressing at room temperature, which confirmed by FTIR, XPS, and XRD tests. According to the results of mechanical tests, the composites with filling weights of MSiCw and MGO, which were found to be 1% and 0.3%, presented tensile strength of 94.27 MPa, which was 32% higher than the matrix. With the additional weights amount of 1%MSiCw and 0.2%MGO, the impact strength of the composites reached 17.46 KJ/m2, which was increased by 81% compared with the matrix. In addition, the reinforcing mechanisms, such as the bridging principle and mechanism of whiskers pulling out, were investigated by analyzing the fracture surface of MSiCw-MGO-PI composites. The results showed that MSiCw and MGO can synergistically improve the mechanical properties of the composites. In addition, the recyclability of the composites valued by the mechanical properties of the composites from regrinding and heat pressing showed that three generations of MSiCw-MGO-PI composites can still maintain high mechanical properties on account of the better dispersion of the reinforcing phases in the matrix from regrinding.

Assembly-induced spin transfer and distance-dependent spin coupling in atomically precise AgCu nanoclusters.

Nanoparticle assembly paves the way for unanticipated properties and applications from the nanoscale to the macroscopic world. However, the study of such material systems is greatly inhibited due to the obscure compositions and structures of nanoparticles (especially the surface structures). The assembly of atomically precise nanoparticles is challenging, and such an assembly of nanoparticles with metal core sizes strictly larger than 1 nm has not been achieved yet. Here, we introduced an on-site synthesis-and-assembly strategy, and successfully obtained a straight-chain assembly structure consisting of Ag77Cu22(CHT)48 (CHT: cyclohexanethiolate) nanoparticles with two nanoparticles separated by one S atom, as revealed by mass spectrometry and single crystal X-ray crystallography. Although Ag77Cu22(CHT)48 bears one unpaired shell-closing electron, the magnetic moment is found to be mainly localized at the S linker with magnetic isotropy, and the sulfur radicals were experimentally verified and found to be unstable after disassembly, demonstrating assembly-induced spin transfer. Besides, spin nanoparticles are found to couple and lose their paramagnetism at sufficiently short inter-nanoparticle distance, namely, the spin coupling depends on the inter-nanoparticle distance. However, it is not found that the spin coupling leads to the nanoparticle growth.

Distinct brain structural abnormalities in attention-deficit/hyperactivity disorder and substance use disorders: A comparative meta-analysis.

As two common mental disorders during the period of adolescence that extend to early adulthood, attention-deficit/hyperactivity disorder (ADHD) and substance use disorders (SUDs) have considerable diagnostic co-occurrence and shared neuropsychological impairments. Our study aimed to identify overlapping and distinct brain structural abnormalities associated with ADHD and SUDs among adolescents and young adults. A systematic literature search on voxel-based morphometry (VBM) studies of ADHD and SUDs was conducted in PubMed and Web of Science. Data were extracted and analyzed to identify brain abnormalities using Seed-based d-Mapping software. Data-driven functional decoding was conducted to identify the psychophysiological functioning associated with brain alterations. 13 and 14 VBM studies for ADHD (619 patients and 483 controls) and SUDs (516 patients and 413 controls), respectively, were included. Patterns of decreased gray matter volume (GMV) were found in the left precentral gyrus, bilateral superior frontal gyri, and left inferior frontal gyrus in the ADHD group compared to the control group. In contrast, individuals with SUDs, relative to controls, were characterized by increased GMV in the left putamen and insula. Comparative analysis indicated larger regional GMV in the right inferior parietal lobule and smaller volumes in the left putamen and left precentral gyrus in the ADHD group than in the SUDs group. Dissociable brain structural abnormalities in adolescents and young adults with ADHD and SUDs potentially implicate different pathogeneses and provide a reference for differential diagnosis and early detection for shared symptomology and comorbidity.

Porphyrin COF and its mechanical pressing-prepared carbon fiber hybrid membrane for ratiometric detection, removal and enrichment of Cd2.

A nitrogen (N), oxygen (O)-rich porphyrin-based covalent organic framework (COF), in which interlayer porphyrin molecules are vertically stacked, is prepared and characterized. As-prepared N,O-rich TpTph COF shows a high adsorption capacity for Cd2+ due to the abundant coordination sites. More interesting, it is found that the formation of COF enlarges the porphyrin ring center space, thus facilitating the Cd2+coordination, and the resulting optical signal changes make the ratiometric detection of Cd2+ possible. Furthermore, using carbon fiber (CF) filaments, which are obtained from low cost and easy-to-obtain actived carbon mask, as support, porphyrin COF-based CF@TpTph membrane is prepared through in-situ growth of COF on the support followed by simple mechanical pressing. The CF@TpTph membrane is demonstrated to work well for both Cd2+ removal and enrichment from soil and water samples, and shows the advantages of ease of handling, robust stability, reduced secondary pollution risk to samples, and good reusability. This work provides a powerful tool for Cd2+ removal and enrichment, exhibits that preparing porphyrin-based COFs is a feasible way to promote the interactions between porphyrin ring and Cd2+, and demonstrates that mechanical pressing is a promising strategy for the design of COF-based monolithic materials to promote the practical applications of COFs.

A graph neural network-based stock forecasting method utilizing multi-source heterogeneous data fusion.

The study of the prediction of stock market volatility is of great significance to rationally control financial market risks and increase excessive investment returns and has received extensive attention from academic and commercial circles. However, as a dynamic and complex system, the stock market is affected by multiple factors and has a comprehensive capability to include complex financial data. Given that the explanatory variables of influencing factors are diverse, heterogeneous and complex, the existing intelligent algorithms have great limitations for the analysis and processing of multi-source heterogeneous data in the stock market. Therefore, this study adopts the edge weight and information transmission mechanism suitable for subgraph data to complete node screening, the gate recurrent unit (GRU) and long short-term memory (LSTM) to aggregate subgraph nodes. The compiled data contain the metapaths of three types of index data, and the introduction of the association relationship attention dimension effectively mines the implicit meanings of multi-source heterogeneous data. The metapath attention mechanism is combined with a graph neural network to complete the classification of multi-source heterogeneous graph data, by which the prediction of stock market volatility is realized. The results show that the above method is feasible for the fusion of heterogeneous stock market data and the mining of implicit semantic information of association relations. The accuracy of the proposed method for the prediction of stock market volatility in this study is 16.64% higher than that of the dimensional reduction index and 14.48% higher than that of other methods for the fusion and prediction of heterogeneous data using the same model.

Rate and risk factors of recurrent immune checkpoint inhibitor-related pneumonitis in patients with lung cancer.

Background: Immune checkpoint inhibitors (ICIs) have become standard treatments for lung cancer patients. Immune checkpoint inhibitor-related pneumonitis (CIP) was the leading cause of death among ICIs-related adverse events (irAEs). Recurrent episodes of CIP without rechallenge of ICIs were reported in several cases and maybe a unique feature of CIP. Knowledge gaps remain regarding the rate and risk factors associated to CIP's recurrence. Methods: Data from 1,102 lung cancer patients receiving ICIs treatment between January 2016 and January 2021 were retrospectively collected and analyzed. CIP was diagnosed according to typical clinical features and/or new typical imaging changes. Recurrence of CIP (CIP-R) was defined as recurrent CIP after initial CIP improved after proper treatment. Logistic regression was used to assess risk factors associated with CIP recurrence. Results: Eighty out of 1,102 (7.26%) patients were diagnosed with CIP. Twenty of those 78 (25.64%) patients suffered CIP-R, 2 patients died and were therefore excluded from the denominator. The median onset of initial pneumonitis for patients without and with recurrence was 3.49 months [interquartile range (IQR), 0.26-31.93 months] and 2.78 months (IQR, 1.22-20.93 months), respectively (P=0.48). The median interval duration between initial CIP and CIP-R was 1.54 months (IQR, 0.98-16.70 months). Recurrence of CIP was more common in males (P=0.03), squamous histology (P=0.016), and in patients who received chest radiotherapy (P=0.049). The duration of prednisolone equivalent dose ≥15 mg/day in CIP-R was significantly shorter, at 3.71 weeks (2.86-6.57 weeks) compared with 6.36 weeks in those without recurrence (IQR, 3.12-9.86 weeks) (P=0.001). Non-squamous histology [odds ratio (OR), 0.182; 95% confidence interval (CI): 0.038-0.860; P=0.031] and prolonged administration of prednisolone equivalent dose ≥15 mg/day for more than 4 weeks (OR, 0.082; 95% CI: 0.02-0.342; P=0.001) were independently associated with a decreased odds of CIP-R development. Conclusions: CIP-R in a real-world lung cancer cohort is not uncommon, both in patients with and without rechallenge of ICIs. A duration of prednisolone equivalent dose ≥15 mg/day of at least 4 weeks during the tapering process of corticosteroids were recommend in patients with CIP.

Dorsal premammillary projection to periaqueductal gray controls escape vigor from innate and conditioned threats.

Escape from threats has paramount importance for survival. However, it is unknown if a single circuit controls escape vigor from innate and conditioned threats. Cholecystokinin (cck)-expressing cells in the hypothalamic dorsal premammillary nucleus (PMd) are necessary for initiating escape from innate threats via a projection to the dorsolateral periaqueductal gray (dlPAG). We now show that in mice PMd-cck cells are activated during escape, but not other defensive behaviors. PMd-cck ensemble activity can also predict future escape. Furthermore, PMd inhibition decreases escape speed from both innate and conditioned threats. Inhibition of the PMd-cck projection to the dlPAG also decreased escape speed. Intriguingly, PMd-cck and dlPAG activity in mice showed higher mutual information during exposure to innate and conditioned threats. In parallel, human functional magnetic resonance imaging data show that a posterior hypothalamic-to-dlPAG pathway increased activity during exposure to aversive images, indicating that a similar pathway may possibly have a related role in humans. Our data identify the PMd-dlPAG circuit as a central node, controlling escape vigor elicited by both innate and conditioned threats.

Coordination of escape and spatial navigation circuits orchestrates versatile flight from threats.

Naturalistic escape requires versatile context-specific flight with rapid evaluation of local geometry to identify and use efficient escape routes. It is unknown how spatial navigation and escape circuits are recruited to produce context-specific flight. Using mice, we show that activity in cholecystokinin-expressing hypothalamic dorsal premammillary nucleus (PMd-cck) cells is sufficient and necessary for context-specific escape that adapts to each environment's layout. In contrast, numerous other nuclei implicated in flight only induced stereotyped panic-related escape. We reasoned the dorsal premammillary nucleus (PMd) can induce context-specific escape because it projects to escape and spatial navigation nuclei. Indeed, activity in PMd-cck projections to thalamic spatial navigation circuits is necessary for context-specific escape induced by moderate threats but not panic-related stereotyped escape caused by perceived asphyxiation. Conversely, the PMd projection to the escape-inducing dorsal periaqueductal gray projection is necessary for all tested escapes. Thus, PMd-cck cells control versatile flight, engaging spatial navigation and escape circuits.

Genes Influencing Phage Host Range in Staphylococcus aureus on a Species-Wide Scale.

Staphylococcus aureus is a human pathogen that causes serious diseases, ranging from skin infections to septic shock. Bacteriophages (phages) are both natural killers of S. aureus, offering therapeutic possibilities, and important vectors of horizontal gene transfer (HGT) in the species. Here, we used high-throughput approaches to understand the genetic basis of strain-to-strain variation in sensitivity to phages, which defines the host range. We screened 259 diverse S. aureus strains covering more than 40 sequence types for sensitivity to eight phages, which were representatives of the three phage classes that infect the species. The phages were variable in host range, each infecting between 73 and 257 strains. Using genome-wide association approaches, we identified putative loci that affect host range and validated their function using USA300 transposon knockouts. In addition to rediscovering known host range determinants, we found several previously unreported genes affecting bacterial growth during phage infection, including trpA, phoR, isdB, sodM, fmtC, and relA We used the data from our host range matrix to develop predictive models that achieved between 40% and 95% accuracy. This work illustrates the complexity of the genetic basis for phage susceptibility in S. aureus but also shows that with more data, we may be able to understand much of the variation. With a knowledge of host range determination, we can rationally design phage therapy cocktails that target the broadest host range of S. aureus strains and address basic questions regarding phage-host interactions, such as the impact of phage on S. aureus evolution.IMPORTANCEStaphylococcus aureus is a widespread, hospital- and community-acquired pathogen, many strains of which are antibiotic resistant. It causes diverse diseases, ranging from local to systemic infection, and affects both the skin and many internal organs, including the heart, lungs, bones, and brain. Its ubiquity, antibiotic resistance, and disease burden make new therapies urgent. One alternative therapy to antibiotics is phage therapy, in which viruses specific to infecting bacteria clear infection. In this work, we identified and validated S. aureus genes that influence phage host range-the number of strains a phage can infect and kill-by testing strains representative of the diversity of the S. aureus species for phage host range and associating the genome sequences of strains with host range. These findings together improved our understanding of how phage therapy works in the bacterium and improve prediction of phage therapy efficacy based on the predicted host range of the infecting strain.

Knowledge, Attitude, and Practices of Antibiotics and Antibiotic Resistance Among Chinese Pharmacy Customers: A Multicenter Survey Study.

BACKGROUND: Resistance to antibiotics is one of the major global health challenges. An adequate understanding of the public regarding rational antibiotic use is a prerequisite to limit progression in antibiotic resistance. This study aimed to investigate the knowledge, attitude, and practices (KAP) of antibiotics and antibiotic resistance among customers visiting community pharmacies. METHODS: This study was undertaken in three capital cities in China during March 2019 and July 2019 by using a questionnaire of 28 items. The questionnaire had four parts, including sociodemographic characteristics, KAP about antibiotics, and antibiotic resistance. A systematic random sampling approach was used to recruit the participants. Kruskal-Wallis and Mann-Whitney tests were carried out for data analysis. RESULTS: The response rate was 66.7% (1800/2700). Out of the total, only 9.7% of the customers had good knowledge about antibiotics. Nearly half of the participants were unable to differentiate between antibiotics, and anti-inflammatory drugs (n = 820, 45.6%, Median = 2, IQR = 1). Most of the customers were of the view that the use of over the counter antibiotics in pregnant women is unsafe (n = 1307, 72.6%, Median = 2, IQR = 0). Almost half of the participants disagreed that costly antibiotics are more effective and have fewer side effects (n = 897, 49.9%, Median = 3, IQR = 1). Only 22.3% of participants said that they always finish the course of antibiotic treatment (n = 401, 22.3%, Median = 3, IQR = 1). CONCLUSION: The knowledge of Chinese pharmacy consumers was inadequate, and a lack of good attitudes and practices in certain aspects of antibiotic use was observed. Educational interventions are needed to increase public knowledge of antibiotics.

A Universal Electrolyte Formulation for the Electrodeposition of Pristine Carbon and Polypyrrole Composites for Supercapacitors.

Electrodeposition of conducting polymer-carbon composites from an electrolyte precursor solution is a facile one-step approach to fabricate device-ready electrodes for energy storage. A key challenge in this approach is the dispersion of the carbon nanomaterials with the aqueous precursor solution with previous approaches either heavily oxidizing the carbon nanomaterials or using high concentrations of anionic surfactants as dopants. However, the former reduces the electrical conductivity of carbon, while the latter reduces the ionic mobility of the conducting polymer due to the large anion size. Herein, for the first time we present a quaternary electrolyte formulation for the fabrication of pristine carbon and polypyrrole (PPy) composites that does not sacrifice either electron or ion mobility. The electrolyte uses lithium perchlorate (20 mM) as a supporting electrolyte and dopant, sodium dodecylbenzenesulfonate at a very low concentration (1.43 mM) as a surfactant, together with pristine carbon nanomaterials and pyrrole monomers. The order of magnitude difference between the concentration of the dopant and surfactant ion allows the as-deposited PPy to be doped predominantly by small-sized and mobile perchlorate anions. Composites of PPy with carbon black, carbon nanotubes, and electrochemical exfoliated graphene (EEG) have been successfully prepared using this new quaternary electrolyte. The as-fabricated PPy/EEG composite electrodes showed a specific capacitance of 348.8 F g-1 with a high rate capability (190.7 F g-1 at 71 A g-1). Supercapacitor devices based on the PPy/EEG composite electrodes exhibit a high rate behavior up to 500 mV s-1 and a long cycle life of 5000 cycles.

Perspective of community pharmacists about community-based antimicrobial stewardship programs. A multicenter cross-sectional study from China.

Background: Antimicrobial stewardship programs (ASPs) are commonly used worldwide to tackle antimicrobial resistance. The current study aimed to investigate the perspective of pharmacists on community-based ASPs in China.Methods: A multicenter cross-sectional study was conducted in the capital cities of three different provinces of China between March 2019 and July 2019. A systematic random sampling method was used to recruit respondents.Results: A response rate of 87.4% (416/476) was obtained. A large number of respondents (n = 308, 74.0%) believed that ASPs are vital to improving patient care (Median = 4, IQR = 2). Approximately one-third of the respondents (n = 142, 34.1%) always ask patients about their knowledge related to antimicrobials (Median = 4, IQR = 2). Additionally, a considerable number of respondents (n = 127, 30.5%) always, or often (n = 117, 28.1%) collaborated with other healthcare professionals (Median = 4, IQR = 2). Age, gender, and experience were observed to have a significant association (p < 0.05) with median scores of knowledge about antibiotics, perceptions, and practices on ASPs.Conclusions: The perceptions of pharmacists regarding ASPs were positive. However, gaps in knowledge about some aspects of antibiotics and participation in ASPs were found. The development of regional community-based ASPs is urgently required.

Three Polymethoxyflavones Purified from Ougan (Citrus reticulata Cv. Suavissima) Inhibited LPS-Induced NO Elevation in the Neuroglia BV-2 Cell Line via the JAK2/STAT3 Pathway.

In order to establish an efficient method for separation of polymethoxyflavones (PMFs) and explore the anti-inflammatory mechanism of PMF monomers, a citrus variety rich in PMFs, Ougan (Citrus reticulata cv. Suavissima), was selected, and three monomers, including nobiletin, tangeretin, and 5-demethylnobiletin, were purified by ultrasonic-assisted extraction, solid phase extraction, and high-speed countercurrent chromatography separation. UPLC-MS was used to identify the three monomers. UPLC determined purities of 99.87% to nobiletin, 99.76% to tangeretin, and 98.75% to 5-demethylnobiletin with the standard curve method. A lipopolysaccharide (LPS)-induced NO releasing model was performed in the mouse microglia BV-2 cell line. Results illustrated that PMF monomers inhibited the NO release and the inflammation-related cytokines, including IL-1ß, IL-6, and TNFα elevation. QRT-PCR revealed that PMFs alleviated LPS-induced upregulation of iNOS, IL-6, JAK2, TNFα, IL-1ß, and NF-κB and LPS-induced downregulation of IκBα, while they did not affect TLR1, TLR2, TLR4, and TLR6. STAT3 expression was repressed by tangeretin and 5-demethylnobiletin, but not by nobiletin. Western blot assay also showed a suppression of expression and phosphorylation of JAK2 by all three PMF monomers, while STAT3 phosphorylation was restrained by tangeretin and 5-demethylnobiletin. The mechanism was primarily verified by the JAK2 inhibitor Ruxolitinib and the STAT3 inhibitor Stattic.

Identification of phenolic compounds from a unique citrus species, finger lime (Citrus australasica) and their inhibition of LPS-induced NO-releasing in BV-2 cell line.

In this study, a unique citrus species (Citrus australasica) was selected, and its fruit characteristics, phenolic compounds and ability to inhibit inflammation were preliminarily studied. Finger lime fruits showed distinctive features in shape, size, weight, colour, total soluble solids, water-soluble pectin, sugar and acids contents. Combining UPLC-HRMS and UPLC-DAD analysis, 31 phenolics, 1 secoiridoid derivative and 1 neolignan glycoside were preliminarily identified and quantified. The phenolics composition of finger limes showed cultivar and tissue specificity. Antioxidant evaluation showed that extracts from finger lime cultivar of 'XiangBin' exhibited better antioxidant capacities than cultivar of 'LiSiKe', especially in peel. LPS-induced NO-releasing model was performed in the mouse microglia BV-2 cell line. Results illustrated that finger limes inhibited the NO-releasing and the inflammation-related cytokines including IL-1ß, IL-6 and TNFα elevation. QRT-PCR revealed that finger lime extracts alleviated LPS-induced upregulation of iNOS, IL-6, JAK2, TNFα, TLR2, TLR4, IL-1ß, NF-κB and LPS-induced downregulation of IκBα. This study may expand our knowledge on the physiochemical characteristics and bioactive properties of citrus fruits.