Dual-Coating of Fluorinated Polydimethylsiloxane/Fluorinated SiO2 Nanoparticles for Superhydrophobic and High-Efficiency Bacteriostatic Surface.

A simple two-step spray method is used to prepare superhydrophobic and bacteriostatic surfaces, involving dual-coating with polydimethylsiloxane-normal-fluorine (PDMS-NF) or branched-fluorine (PDMS-BF) in combination with fluorinated silica nanoparticles (FSiO2 -NPs) using a spray technique. This approach has the potential to create surfaces with both water-repellent and antimicrobial properties, which could be useful in a variety of applications. It is noteworthy that the dual-coating on cotton fabric exhibited an impressive dual-scale roughness and achieved superhydrophobicity with a water contact angle of 158° and a hysteresis of less than 3°. Additionally, the coating was subjected to an ultra-high concentration of bacteria (109 CFU/mL) and was still able to inhibit more than 80 % of attachment, demonstrating its effectiveness as a bacteriostatic surface.

Solar CO2 Reduction Enabled by Cascade Hole Migration.

Solar-powered photocatalytic conversion of CO2 to hydrocarbon fuels represents an emerging approach to solving the greenhouse effect. However, low charge separation efficiency, deficiency of surface catalytic active sites, and sluggish charge-transfer kinetics, together with the complicated reaction pathway, concurrently hinder the CO2 reduction. Herein, we show the rational construction of transition metal chalcogenides (TMCs) heterostructure CO2 reduction photosystems, wherein the TMC substrate is tightly integrated with amorphous oxygen-containing cobalt sulfide (CoSOH) by a solid non-conjugated polymer, i.e., poly(vinyl alcohol) (PVA), to customize the unidirectional charge-transfer pathway. In this well-defined multilayered nanoarchitecture, the PVA interim layer intercalated between TMCs and CoSOH acts as a hole-relaying mediator and meanwhile boosts CO2 adsorption capacity, while CoSOH functions as a terminal hole-collecting reservoir, stimulating the charge transport kinetics and boosting the charge separation over TMCs. This peculiar interface configuration and charge transport characteristics endow TMC/PVA/CoSOH heterostructures with significantly enhanced visible-light-driven photoactivity and CO2 conversion. Based on the intermediates probed during the photocatalytic CO2 reduction reaction, the photocatalytic mechanism was determined. Our work would inspire sparkling ideas to mediate the charge transfer over semiconductor for solar carbon neutral conversion.

Synthesis of High-Quality Bulk Single-Crystal Black Phosphorus by the Circulating Vapor Growth Approach.

Black phosphorus (BP), a promising two-dimensional (2D) layered semiconductor material, has gained enormous attention due to its impressive properties over the past several years. Although plenty of methods have been developed to synthesize high-quality BP, most of the currently available BP materials still suffer from unsatisfactory crystallization, purity, and stability in air, hindering their practical application. A facile approach to synthesizing ultrahigh-quality single-crystal BP is of significance to shed light on the nature of 2D semiconductor materials and their massive application. In this work, we present the facile and efficient circulating vapor growth approach to growing bulk single-crystal BP. The as-grown BP material features high crystallinity and ultrahigh purity (higher than 99.999 at %), exceeding those of all the previously reported and some commercially available BP crystals. It also maintains excellent stability in air and water after 15 consecutive days of test. Moreover, the as-synthesized BP material features good thermal stability, oxidation resistance, and excellent electrical properties, as well. This study provides a new approach for the fabrication of ultrahigh-quality BP material and thus promotes its application.

Exploring the constitutive activation mechanism of the class A orphan GPR20.

GPR20, an orphan G protein-coupled receptor (GPCR), shows significant expression in intestinal tissue and represents a potential therapeutic target to treat gastrointestinal stromal tumors. GPR20 performs high constitutive activity when coupling with Gi. Despite the pharmacological importance of GPCR constitutive activation, determining the mechanism has long remained unclear. In this study, we explored the constitutive activation mechanism of GPR20 through large-scale unbiased molecular dynamics simulations. Our results unveil the allosteric nature of constitutively activated GPCR signal transduction involving extracellular and intracellular domains. Moreover, the constitutively active state of the GPR20 requires both the N-terminal cap and Gi protein. The N-terminal cap of GPR20 functions like an agonist and mediates long-range activated conformational shift. Together with the previous study, this study enhances our knowledge of the self-activation mechanism of the orphan receptor, facilitates the drug discovery efforts that target GPR20.

Radiotherapy is superior to transarterial chemoembolization as adjuvant therapy after narrow-margin hepatectomy in patients with hepatocellular carcinoma: A single-center prospective randomized study.

BACKGROUND: This study was recruited to compare the efficacy and safety of radiotherapy (RT) and transarterial chemoembolization (TACE) as postoperative adjuvant therapy after narrow-margin hepatectomy in hepatocellular carcinoma (HCC) patients. METHODS: This single-center prospective randomized study was conducted in the Cancer Hospital, Guang Xi Medical University, Nanning. A total of 72 patients who received treatment in this hospital between August 2017 and July 2019 were included and randomly allocated to TACE group (n = 48) and RT group (n = 24). Next, overall survival (OS) and progression-free survival (PFS) rates, recurrence patterns, financial burden, and safety were evaluated. RESULTS: The difference between the RT and TACE groups was not significant in one-, three-, and five-year OS (87.5%, 79.0%, and 62.5% vs. 93.8%, 75.9%, and 63.4%, respectively, P = 0.071) and PFS rates (79.0%, 54.2%, and 22.6% vs. 75.0%, 47.9%, and 32.6%, respectively, P = 0.071). Compared to the TACE group, the RT group had significantly lower intrahepatic recurrence rate (20.8% vs. 52.1%, P = 0.011), higher extrahepatic recurrence rate (37.5% vs. 14.6%, P = 0.034), and no marginal and diffuse recurrences (0% vs. 16.7%, P < 0.05). The mean overall treatment cost was higher (¥62,550.59 ± 4397.27 vs. ¥40,732.56 ± 9210.54, P < 0.01), the hospital stay (15.1 ± 3.7 vs. 11.8 ± 4.1 days, P < 0.01) was longer, and the overall treatment stay (13.3 ± 5.3 vs. 41.29 ± 12.4 days, P < 0.01) was shorter in the TACE group than in the RT group. Besides, both groups did not exhibit significant differences in the frequency and severity of adverse events. CONCLUSION: Both adjuvant TACE and RT can better the OS and PFS of patients with HCC. However, RT has a significantly better performance than TACE in terms of improving intrahepatic recurrence rate, treatment cost and hospital stay.

Branched Aluminum Nanocrystals with Internal Hot Spots: Synthesis and Single-Particle Surface-Enhanced Raman Scattering.

Owing to their unique and sustainable surface plasmonic properties, Al nanocrystals have attracted increasing attention for plasmonic-enhanced applications, including single-particle surface-enhanced Raman scattering (SERS). However, whether Al nanocrystals can achieve single-particle SERS is still unknown, mainly due to the synthetic difficulty of Al nanocrystals with internal gaps. Herein, we report a regrowth method for the synthesis of Al nanohexapods with tunable and uniform internal gaps for single-particle SERS with an enhancement factor of up to 1.79 × 108. The uniform branches of the Al nanohexapods can be systematically tuned regarding their dimensions, terminated facets, and internal gaps. The Al nanohexapods generate hot spots concentrated in the internal gaps due to the strong plasmonic coupling between the branches. A single-particle SERS measurement of Al nanohexapods shows strong Raman signals with maximum enhancement factors comparable to that of Au counterparts. The large enhancement factor indicates that Al nanohexapods are good candidates for single-particle SERS.

[Identification of chemical components in Qinggu San reference sample of classial prescription based on UHPLC-Q/Orbitrap HRMS combined with molecular network technology].

The method of ultra-high performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry(UHPLC-Q/Orbitrap HRMS)combined with molecular network was developed in this study for rapidly analyzing the chemical components of the Qinggu San reference sample of classical prescription. Firstly, an ACQUITY UPLC BEH Shield RP_(18) column(2.1 mm×100 mm, 1.7 µm)was used, and acetonitrile and 0.1% formic acid were taken as the mobile phases for gradient elution. The flow rate was 0.4 mL·min~(-1), and the column temperature was 30 ℃. Under these conditions, the mass spectrum data were collected in both positive and negative ion modes of the heated electrospray ionization source. Subsequently, the mass spectrum data of the Qinggu San reference sample were uploaded to the Global Natural Products Social Molecular Network(GNPS)platform for calculation and analysis, and a visual molecular network was built with Cytoscape 3.8.2 software. On this basis, the chemical components of the Qinggu San reference sample were identified by fragmentation regularity of standard compounds, retention time, accurate relative molecular weight of HR-MS, characteristic fragment ions information, literature, and databases. Finally, a total of 105 chemical components were identified and speculated in the Qinggu San reference sample, including 19 iridoid glycosides, 23 flavonoids, 15 phenylpropanoids, 11 triterpene saponins, and 37 other components. Meanwhile, two of these components are potential new compounds. The method used in this study not only achieved rapid and accurate identification of chemical components in the Qinggu San reference sample and provided a scie-ntific basis for the study of pharmacological substances and quality control of Qinggu San compound preparations but also provided a refe-rence for the rapid identification of chemical components in traditional Chinese medicine compound preparations.

Ex Vivo and In Vivo CD46 Receptor Utilization by Species D Human Adenovirus Serotype 26 (HAdV26).

Human adenovirus serotype 26 (Ad26) is used as a gene-based vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and HIV-1. However, its primary receptor portfolio remains controversial, potentially including sialic acid, coxsackie and adenovirus receptor (CAR), integrins, and CD46. We and others have shown that Ad26 can use CD46, but these observations were questioned on the basis of the inability to cocrystallize Ad26 fiber with CD46. Recent work demonstrated that Ad26 binds CD46 with its hexon protein rather than its fiber. We examined the functional consequences of Ad26 for infection in vitro and in vivo. Ectopic expression of human CD46 on Chinese hamster ovary cells increased Ad26 infection significantly. Deletion of the complement control protein domain CCP1 or CCP2 or the serine-threonine-proline (STP) region of CD46 reduced infection. Comparing wild-type and sialic acid-deficient CHO cells, we show that the usage of CD46 is independent of its sialylation status. Ad26 transduction was increased in CD46 transgenic mice after intramuscular (i.m.) injection but not after intranasal (i.n.) administration. Ad26 transduction was 10-fold lower than Ad5 transduction after intratumoral (i.t.) injection of CD46-expressing tumors. Ad26 transduction of liver was 1,000-fold lower than that ofAd5 after intravenous (i.v.) injection. These data demonstrate the use of CD46 by Ad26 in certain situations but also show that the receptor has little consequence by other routes of administration. Finally, i.v. injection of high doses of Ad26 into CD46 mice induced release of liver enzymes into the bloodstream and reduced white blood cell counts but did not induce thrombocytopenia. This suggests that Ad26 virions do not induce direct clotting side effects seen during coronavirus disease 2019 (COVID-19) vaccination with this serotype of adenovirus. IMPORTANCE The human species D Ad26 is being investigated as a low-seroprevalence vector for oncolytic virotherapy and gene-based vaccination against HIV-1 and SARS-CoV-2. However, there is debate in the literature about its tropism and receptor utilization, which directly influence its efficiency for certain applications. This work was aimed at determining which receptor(s) this virus uses for infection and its role in virus biology, vaccine efficacy, and, importantly, vaccine safety.

Soft, flexible pressure sensors for pressure monitoring under large hydrostatic pressure and harsh ocean environments.

Traditional rigid ocean pressure sensors typically require protection from bulky pressure chambers and complex seals to survive the large hydrostatic pressure and harsh ocean environment. Here, we introduce soft, flexible pressure sensors that can eliminate such a need and measure a wide range of hydrostatic pressures (0.1 MPa to 15 MPa) in environments that mimic the ocean, achieving small size, high flexibility, and potentially low power consumption. The sensors are fabricated from lithographically patterned gold thin films (100 nm thick) encapsulated with a soft Parylene C film and tested in a customized pressure vessel under well-controlled pressure and temperature conditions. Using a rectangular pressure sensor as an example, the resistance of the sensor is found to decrease linearly with the increase of the hydrostatic pressure from 0.1 MPa to 15 MPa. Finite element analysis (FEA) reveals the strain distributions in the pressure sensor under hydrostatic pressures of up to 15 MPa. The effect of geometry on sensor performance is also studied, and radially symmetric pressure sensors (like circular and spike-shaped) are shown to have more uniform strain distributions under large hydrostatic pressures and, therefore, have a potentially enhanced pressure measurement range. Pressure sensors of all geometries show high consistency and negligible hysteresis over 15 cyclic tests. In addition, the sensors exhibit excellent flexibility and operate reliably under a hydrostatic pressure of 10 MPa for up to 70 days. The developed soft pressure sensors are promising for integration with many platforms including animal tags, diver equipment, and soft underwater robotics.

Self-Transformation of Atomically Precise Alloy Nanoclusters to Plasmonic Alloy Nanocrystals: Evaluating Photosensitization in Solar Water Oxidation.

Atomically precise alloy nanoclusters (NCs) inherit the advantages of homometal NC counterparts such as atomic stacking fashion, quantum confinement effect, and enriched catalytic active sites and simultaneously possess the advantageous physicochemical properties such as significantly enhanced photostability, ideal photosensitization efficiency, and favorable energy band structure. Nevertheless, elucidation of the roles of alloy NCs and alloy nanocrystals (NYs) in boosting solar water oxidation has so far not yet been reported owing to the deficiency of applicable alloy NC photosystems. Herein, utilizing the generic thermal-induced self-transformation of alloy NCs to alloy NYs, we comprehensively explore the photosensitization properties of glutathione (GSH)-capped alloy NCs (AgxAu1-x@GSH and CuxAu1-x@GSH) and the corresponding alloy NY (AgAu and CuAu) counterparts in solar water oxidation reaction. The results imply that photoelectrons of alloy NCs surpass the hot electrons over plasmonic alloy NYs in stimulating the PEC water oxidation reaction. The photoelectrons of alloy NCs demonstrate lower interfacial charge-transfer resistance, longer carrier lifetime, and a more enhanced photosensitization effect with respect to the plasmonic alloy NYs, contributing to the significantly boosted photoelectrochemical water oxidation activities. Moreover, we found that our result is universal.

Molecular Physiological Evidence for the Role of Na+-Cl- Co-Transporter in Branchial Na+ Uptake in Freshwater Teleosts.

The gills are the major organ for Na+ uptake in teleosts. It was proposed that freshwater (FW) teleosts adopt Na+/H+ exchanger 3 (Nhe3) as the primary transporter for Na+ uptake and Na+-Cl- co-transporter (Ncc) as the backup transporter. However, convincing molecular physiological evidence to support the role of Ncc in branchial Na+ uptake is still lacking due to the limitations of functional assays in the gills. Thus, this study aimed to reveal the role of branchial Ncc in Na+ uptake with an in vivo detection platform (scanning ion-selective electrode technique, SIET) that has been recently established in fish gills. First, we identified that Ncc2-expressing cells in zebrafish gills are a specific subtype of ionocyte (NCC ionocytes) by using single-cell transcriptome analysis and immunofluorescence. After a long-term low-Na+ FW exposure, zebrafish increased branchial Ncc2 expression and the number of NCC ionocytes and enhanced gill Na+ uptake capacity. Pharmacological treatments further suggested that Na+ is indeed taken up by Ncc, in addition to Nhe, in the gills. These findings reveal the uptake roles of both branchial Ncc and Nhe under FW and shed light on osmoregulatory physiology in adult fish.

SRY is a Key Mediator of Sexual Dimorphism in Hepatic Ischemia/Reperfusion Injury.

OBJECTIVES: To identify the role and mechanism of a male specific gene, SRY, in I/R-induced hepatic injury. BACKGROUND: Males are more vulnerable to I/R injury than females. However, the mechanism of these sex-based differences remains poorly defined. METHODS: Clinicopathologic data of patients who underwent hepatic resection were identified from an international multi-institutional database. Liver specific SRY TG mice were generated, and subjected to I/R insult with their littermate WT controls in vivo. In vitro experiments were performed by treating primary hepatocytes from TG and WT mice with hypoxia/reoxygen-ation stimulation. RESULTS: Clinical data showed that postoperative aminotransferase level, incidence of overall morbidity and liver failure were markedly higher among 1267 male versus 508 female patients who underwent hepatic resection. SRY was dramatically upregulated during hepatic I/R injury. Overexpression of SRY in male TG mice and ectopic expression of SRY in female TG mice exacerbated liver I/R injury compared with WTs as manifested by increased inflammatory reaction, oxidative stress and cell death in vivo and in vitro. Mechanistically, SRY interacts with Glycogen synthase kinase-3ß (GSK-3ß) and ß-catenin, and promotes phosphorylation and degradation of ß-catenin, leading to suppression of the downstream FOXOs, and activation of NF-κBand TLR4 signaling. Furthermore, activation of ß-catenin almost completely reversed the SRYoverexpression-mediated exacerbation of hepatic I/R damage. CONCLUSIONS: SRY is a novel hepatic I/R mediator that promotes hepatic inflammatory reaction, oxidative stress and cell necrosis via inhibiting Wnt/ß-catenin signaling, which accounts for the sex-based disparity in hepatic I/R injuries.

Excreted Antibiotics May Be Key to Emergence of Increasingly Efficient Antibiotic Resistance in Food Animal Production.

At a time when antibiotic resistance is seemingly ubiquitous worldwide, understanding the mechanisms responsible for successful emergence of new resistance genes may provide insights into the persistence and pathways of dissemination for antibiotic-resistant organisms in general. For example, Escherichia coli strains harboring a class A ß-lactamase-encoding gene (blaCTX-M-15) appear to be displacing strains that harbor a class C ß-lactamase gene (blaCMY-2) in Washington State dairy cattle. We cloned these genes with native promoters into low-copy-number plasmids that were then transformed into isogenic strains of E. coli, and growth curves were generated for two commonly administered antibiotics (ampicillin and ceftiofur). Both strains met the definition of resistance for ampicillin (≥32 µg/mL) and ceftiofur (≥16 µg/mL). Growth of the CMY-2-producing strain was compromised at 1,000 µg/mL ampicillin, whereas the CTX-M-15-producing strain was not inhibited in the presence of 3,000 µg/mL ampicillin or with most concentrations of ceftiofur, although there were mixed outcomes with ceftiofur metabolites. Consequently, in the absence of competing genes, E. coli harboring either gene would experience a selective advantage if exposed to these antibiotics. Successful emergence of CTX-M-15-producing strains where CMY-2-producing strains are already established, however, requires high concentrations of antibiotics that can only be found in the urine of treated animals (e.g., >2,000 µg/mL for ampicillin, based on literature). This ex vivo selection pressure may be important for the emergence of new and more efficient antibiotic resistance genes and likely for persistence of antibiotic-resistant bacteria in food animal populations. IMPORTANCE We studied the relative fitness benefits of a cephalosporin resistance enzyme (CTX-M-15) that is displacing a similar enzyme (CMY-2), which is extant in E. coli from dairy cattle in Washington State. In vitro experiments demonstrated that CTX-M-15 provides a significant fitness advantage, but only in the presence of very high concentrations of antibiotic that are only found when the antibiotic ampicillin, and to a lesser extent ceftiofur, is excreted in urine from treated animals. As such, the increasing prevalence of bacteria with blaCTX-M-15 is likely occurring ex vivo. Interventions should focus on controlling waste from treated animals and, when possible, selecting antibiotics that are less likely to impact the proximal environment of treated animals.

Vibronic and Environmental Effects in Simulations of Optical Spectroscopy.

Including both environmental and vibronic effects is important for accurate simulation of optical spectra, but combining these effects remains computationally challenging. We outline two approaches that consider both the explicit atomistic environment and the vibronic transitions. Both phenomena are responsible for spectral shapes in linear spectroscopy and the electronic evolution measured in nonlinear spectroscopy. The first approach utilizes snapshots of chromophore-environment configurations for which chromophore normal modes are determined. We outline various approximations for this static approach that assumes harmonic potentials and ignores dynamic system-environment coupling. The second approach obtains excitation energies for a series of time-correlated snapshots. This dynamic approach relies on the accurate truncation of the cumulant expansion but treats the dynamics of the chromophore and the environment on equal footing. Both approaches show significant potential for making strides toward more accurate optical spectroscopy simulations of complex condensed phase systems.

Pan-KRAS inhibitors suppress proliferation through feedback regulation in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is currently one of the most lethal cancers worldwide. Several basic studies have confirmed that Kirsten rat sarcoma virus (KRAS) is a key driver gene for the occurrence of PDAC, and KRAS mutations have also been found in most patients in clinical studies. In this study, two pan-KRAS inhibitors, BI-2852 and BAY-293, were chosen as chemical probes to investigate their antitumor potency in PDAC. Their inhibitory effects on KRAS activation were validated in vitro and their antiproliferative potency in PDAC cell lines were profiled, with half-maximal inhibitory concentration (IC50) values of approximately 1 µM, demonstrating the therapeutic potential of pan-KRAS inhibitors in the treatment of PDAC. However, feedback regulation in the KRAS pathway weakened inhibitor activity, which was observed by a 50 times difference in BAY-293 from in vitro activity. Furthermore, pan-KRAS inhibitors effectively inhibited cell proliferation in 3D organoids cultured from PDAC patient samples; however, there were some variations between individuals. These results provide a sufficient theoretical foundation for KRAS as a clinical therapeutic target and for the application of pan-KRAS inhibitors in the treatment of PDAC, with important scientific significance in translational medicine.

In Vivo Functional Assay in Fish Gills: Exploring Branchial Acid-Excreting Mechanisms in Zebrafish.

Molecular and physiological analyses in ionoregulatory organs (e.g., adult gills and embryonic skin) are essential for studying fish ion regulation. Recent progress in the molecular physiology of fish ion regulation was mostly obtained in embryonic skin; however, studies of ion regulation in adult gills are still elusive and limited because there are no direct methods for in vivo functional assays in the gills. The present study applied the scanning ion-selective electrode technique (SIET) in adult gills to investigate branchial H+-excreting functions in vivo. We removed the opercula from zebrafish and then performed long-term acid acclimation experiments. The results of Western blot and immunofluorescence showed that the protein expression of H+-ATPase (HA) and the number of H+-ATPase-rich ionocytes were increased under acidic situations. The SIET results proved that the H+ excretion capacity is indeed enhanced in the gills acclimated to acidic water. In addition, both HA and Na+/H+ exchanger (Nhe) inhibitors suppressed the branchial H+ excretion capacity, suggesting that H+ is excreted in association with HA and Nhe in zebrafish gills. These results demonstrate that SIET is effective for in vivo detection in fish gills, representing a breakthrough approach for studying the molecular physiology of fish ion regulation.

The intracranial tumor segmentation challenge: Contour tumors on brain MRI for radiosurgery.

We report the set-up of the Intracranial Tumor Segmentation (ICTS) dataset. This dataset was retrieved from clinical work of radiosurgery, contoured by qualified neurosurgeons and radiation oncologists. It contains contrast-enhanced T1-weighted images of 1500 patients, together with the labels of tumors to be treated. The ICTS image data and manual annotations continue to be publicly available through an online evaluation system as an ongoing benchmarking resource.

Peri-radiosurgical administration of bevacizumab improves radiographic response to single and fractionated stereotactic radiosurgery for large brain metastasis.

INTRODUCTION: Stereotactic radiosurgery (SRS) is a standard of care for brain metastases (BM) patients, yet large BM are at a greater risk for radionecrosis and local progression (LP). Concomitant bevacizumab and radiotherapy has been shown to improve outcomes in primary and metastatic brain tumors. This retrospective study investigated the efficacy and safety of concurrent bevacizumab and SRS for large BM. METHODS: From 2015 to 2019, patients with a BM diameter ≥ 2 cm who received either combination therapy (n = 49, SRS + BVZ group), or SRS alone (n = 73, SRS group) were enrolled. Bevacizumab was given peri-radiosurgically with a 2-week interval. Radiographic response was assessed using the RECIST version 1.1. Competing risk and logistic regression analysis were performed to evaluate prognostic factors. RESULTS: Radiographic response was achieved in 41 patients (84%) in the SRS + BVZ group and 37 patients (51%) in the SRS group (p = 0.001). In the multivariate regression analysis, concurrent bevacizumab was independently associated with a better radiographic response (p = 0.003). The cumulative incidences of LP and ≥ grade 2 radionecrosis at 12 months between the SRS + BVZ group and SRS group were 2% versus 6.8%, and 14.3% versus 14.6%, respectively. For patients with BM size ≥ 3 cm, the cumulative incidence of LP was significantly lower in the SRS + BVZ group (p = 0.03). No ≥ grade 4 toxicity was observed in either group. CONCLUSIONS: Concurrent bevacizumab and SRS for large BM is highly effective, with a better radiographic response and minimal excessive treatment-related toxicities. Peri-radiosurgical bevacizumab preferentially reduced the risk of LP, especially for BM size ≥ 3 cm.

Non-linear dose-response relation between urinary levels of nicotine and its metabolites and cognitive impairment among an elderly population in China.

BACKGROUND: Active smoking and exposure to environmental tobacco smoke may be related to cognitive function decline. We assessed the associations of urinary levels of nicotine and its metabolites with cognitive function. METHODS: A total of 553 elder adults at high risk of cognitive impairment and 2212 gender- and age-matched individuals at low risk of cognitive impairment were selected at a ratio of 1: 4 from the remained individuals (n = 6771) who completed the baseline survey of the Shenzhen Ageing-Related Disorder Cohort, after excluding those with either Alzheimer's disease, Parkinson's syndrome or stroke as well as those with missing data on variables (including active and passive smoking status, Mini-Cog score). Urinary levels of nicotine and its metabolites and cognitive function for all individuals were measured by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) and assessed using the Mini-Cog test, respectively. Associations of urinary levels of nicotine and its metabolites with cognitive function were analyzed by conditional logistic regression models. RESULTS: Individuals in the highest tertile of urinary OHCotGluc (OR: 1.52, 95%CI: 1.19-1.93) or NNO (OR: 1.50, 95%CI: 1.16-1.93) levels as well as in the second tertile of urinary ∑Nic level (OR: 1.43, 95%CI: 1.13-1.82) were at higher risk of cognitive impairment compared with those in the corresponding lowest tertile. Restricted cubic spline models revealed the non-linear dose-response relationships between urinary levels of OHCotGluc, NNO or ∑Nic and the risk of cognitive impairment. CONCLUSIONS: Urinary levels of OHCotGluc, NNO or ∑Nic exhibited a non-linear dose-response relationship with cognitive function in the urban elderly.

Analysis of bioactive components and pharmacokinetics of Caulophyllum robustum in rat plasma after oral administration by UPLC-ESI-MS/MS.

A UPLC-MS/MS method was developed and validated the determination and pharmacokinetic study of magnoflorine, cauloside C, hederagenin, and oleanolic acid from Caulophyllum robustum. Digoxin was used as the internal standard. The pretreated plasma samples were carried out on a Waters ACQUITYUPLC HSS T3 column at 35 °C with a mobile phase of acetonitrile-water (90:10, v/v) at a flow rate of 0.2 mL/min. This article describes the most simple, sensitive, and validated UPLC-MS/MS method to date for the simultaneous successful determination of four compounds in rat plasma after oral administration of the extract of C. robustum and their pharmacokinetic studies.