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Five new iridoid glucosides, cannabifolisides A–E (1 – 5), together with nine analogues (6 – 14), were isolated from the leaves of Vitex negundo var. cannabifolia. Their structures were elucidated by spectroscopic data (NMR, UV, IR, and MS) analyses and comparison of their spectroscopic and physical data with the literature values. The protective effect of isolated compounds on human gastric epithelial cells were evaluated by measuring the enhanced cell viability of GES-1 cell insulted by TCA. Among these, compounds 4, 6, 8, 10, 12, and 14 remarkably increased the cell viability in a concentration-depend manner.

Photodynamic therapy (PDT) has emerged as a potential clinical strategy for tumor therapy. It can generate reactive oxygen species (ROS) to cause the chemical damage of tumor cells and promote the immune killing effects of T cells on tumor cells in the presence of enough oxygen and PDT drugs. However, most solid tumors are in a state of oxygen deficiency, which seriously limit the efficacy of PDT in generation enough ROS. Besides, few safe PDT drugs with ideal pharmacokinetic behavior are available in the clinic, which severely limits the clinical transformation and application of PDT. Herein, we utilized manganese chloride to mineralize the hydrophilic indocyanine green/albumin polyplexes (ICG@BSA@MnO2) by using bio-mineralized method to solve these problems of PDT. These ICG@BSA@MnO2 nanoparticles could circulate in the blood for a long period other than quickly removed from body after 30 min like free ICG. When accumulated at the tumor site, ICG was responsively released in the presence of hydrogen peroxide. Apart this, the tumor hypoxia microenvironment was also reversed owing to enhanced O2 generation by the reaction of MnO2 with hydrogen peroxide. Benefits from the rich accumulation of ICG and ameliorated tumor hypoxia in the tumor sites, the enhanced generation of ROS could successfully promote the distribution of CD3+ and CD8+ T cells inside the tumors, which then lead to the amplified efficacy of PDT in both CT26 and B16F10 tumor models without causing any side effects.

Seventeen quinolizidine alkaloids, including two new ones, 5-hydoxy-7,11-dehydromatrine (1) and 11-hydroxylupanine (2), were isolated from the aerial parts of Sophora tonkinensis. The structures of the isolates were elucidated using 1D and 2D NMR analyses, as well as HR-ESI-MS spectroscopic data. The anti-inflammatory activities of all the isolates on NO production in RAW 264.7 cells stimulated by lipopolysaccharide (LPS) were evaluated. Compounds 3, 4, 13, and 14 were shown to have moderate anti-inflammatory effects.

Thirteen undescribed dihydroagarofuran sesquiterpenes, hypogricins A-M, were isolated from the twigs of Tripterygium hypoglaucum. Extensive spectroscopic techniques were used for the structural elucidation of these compounds. All the compounds showed no significant cytotoxicity against adriamycin-sensitive HepG-2 and adriamycin-resistant HepG-2/Adr cell lines. When HepG-2/Adr cell line was co-treated with those compounds plus adriamycin, hypogricins A and B showed potent activity to reverse multidrug resistance (MDR) of HepG2/Adr cells to adriamycin (reversal fold: RF = 102 and 200, respectively). In addition, hypogricins E, H, and L showed moderate activity to inhibit NO production in LPS-stimulated RAW264.7 cells with the IC50 of 22.3, 17.8, and 19.8 μM, respectively.

Purpose MRI-assisted radiosurgery (MARS) is a modern technique for prostate brachytherapy that provides superior soft tissue contrast. The purpose of this analysis was to evaluate treatment planning factors associated with urinary toxicity, particularly damage to the membranous urethra (MUL) and external urethral sphincter (EUS), after MARS. Material and Methods We retrospectively reviewed 227 patients treated with MARS. Comparisons were made between several factors including preimplantation length of the MUL and EUS dosimetric characteristics after implantation with longitudinal changes in American Urological Association (AUA) urinary symptom score. Results Rates of grade 3 urinary incontinence and obstructive urinary symptoms were 4% and 2%. A piecewise mixed univariate model revealed that MUL and V200, V150, V125, and D5 to the EUS were all associated with increased rates of urinary toxicity over time. On univariate logistic regression, MUL >14.2 mm (odds ratio [OR] 2.03 per cm3, 95% confidence interval [CI] 1.10–3.77, p = 0.025), V125 to the EUS (OR 3.21 cm3, 95% CI 1.18–8.71, p = 0.022), and use of the I-125 isotope (OR 3.45, 95% CI 1.55–7.70, p = 0.001) were associated with subacute urinary toxicity (i.e., that occurring at 4–8 months). Optimal dose-constraint limits to the EUS were determined to be V200 Conclusions MARS brachytherapy provides detailed anatomic information for treatment planning, implantation, and quality assurance. Overall rates of urinary toxicity are low; however, several dosimetric variables associated with the EUS were found to correlate with urinary toxicity.

Background and purpose With an enlarging population of long-term oropharyngeal cancer survivors, dysphagia is an increasingly important toxicity following oropharynx cancer treatment. While lower doses to normal surrounding structures may be achieved with intensity modulated proton therapy (IMPT) compared to photon-based radiation, the clinical benefit is uncertain. Methods and materials Seventy-one patients with stage III/IV oropharyngeal cancer (AJCC 7th edition) undergoing definitive IMPT on a longitudinal prospective cohort study who had completed the MD Anderson Dysphagia Inventory (MDADI) at pre-specified time points were included. Results The majority of patients had HPV-positive tumors (85.9%) and received bilateral neck radiation (81.4%) with concurrent systemic therapy (61.8%). Mean composite MDADI scores decreased from 88.2 at baseline to 59.6 at treatment week 6, and then increased to 74.4 by follow up week 10, 77.0 by 6 months follow up, 80.5 by 12 months follow up, and 80.1 by 24 months follow up. At baseline, only 5.6% of patients recording a poor composite score (lower than 60), compared to 61.2% at treatment week 6, 19.1% at follow up week 10, 13.0% at 6 months follow up, 13.5% at 1 year follow up, and 11.1% at 2 years follow up. Conclusions Patient reported outcomes following IMPT for oropharyngeal cancer demonstrates decreased swallowing function at completion of treatment with relatively rapid recovery by 10 weeks follow up and steady improvement through 2 years. The results are comparable to similar longitudinal studies of photon-based radiotherapy for oropharynx cancer, and suggest that IMPT confers no additional excess toxicity related to swallowing.

Robust Parameter Design (RPD) has been widely applied for improving quality and reliability of products. One of the key drawbacks of applying RPD using Taguchi method is that the stable factors may not be independent of the adjustment factors, resulting in unsatisfactory design. Moreover, the Taguchi method cannot guarantee global optimality since the levels set in the experiment are usually discrete to ensure orthogonal design. In this paper, robust solutions of the stable factors are obtained via a nonlinear model based on polynomial fitting; while the adjustment factors are obtained via interactions analysis so that they are independent of the stable factors. In particular, the values of the adjustment factors are determined by output offset compensation so as to achieve robustness of the design scheme. An example on the design of an aeronautical electrical apparatus is presented to illustrate the procedure. The results show that the proposed method can take full advantage of the nonlinearity in the response and achieve the desired outcome. Keywords: Aeronautical electrical apparatus, Global optimization, Interactions analysis, Polynomial fitting, Robust parameter design

Seven undescribed sesquiterpenoid dimers, commiphomyrones A - G, together with three known analogs, were isolated from the resin of Commiphora myrrha Engl.. The structures of the undescribed compounds were elucidated based on a comprehensive analysis of spectroscopic data (NMR, UV, IR, and MS), and the absolute configurations were defined by comparing the experimental and calculated ECD spectra as well as by performing X-ray crystallographic analysis. All the isolated dimeric sesquiterpenoids feature a 7-oxabicyclo [2.2.1] hept-2-ene moiety formed by the [4 + 2] cycloaddition of two sesquiterpenoids. Commiphomyrones C and G and commiphoratone D showed cytotoxic activity against the HGC-27 cell line with IC

PURPOSE: We report longitudinal patient-reported quality-of-life (QoL) outcomes related to xerostomia in patients with oropharyngeal cancer treated with intensity-modulated proton therapy (IMPT). MATERIALS AND METHODS: Patients treated from May 2012 through December 2016 at a single institution for AJCC7 stage III-IV, M0 oropharyngeal cancer were given the 15-item Xerostomia-Related QoL Scale (XeQoLS) before, during, and for up to 2 years after treatment. We evaluated the evolution of xerostomia-related QoL over that time, and examined potential associations between those measures with clinical characteristics. RESULTS: Sixty-nine patients had XeQoLS scores at baseline and at least once either during or after treatment. The mean (±SD) XeQoLS score (0–4) was 0.24 ± 0.57 at baseline. Subsequent scores were 2.00 ± 1.01 at 6 weeks on treatment, and 1.03 ± 0.76, 0.97 ± 0.78, 0.82 ± 0.69, and 0.70 ± 0.75 at 10 weeks, 6 months, 1 year, and 2 years after treatment, respectively. All were statistically different from baseline (p < 0.001). Univariate analyses demonstrated associations between XeQoLS score and time (p < 0.0001 for each interval), baseline XeQoLS score (p < 0.0001), stage (p = 0.008), N status (p = 0.006), and mean oral cavity dose (p = 0.038), but not for age, sex, T status, receipt of chemotherapy, smoking history, disease site, laterality of neck irradiation, mean parotid dose, or mean submandibular dose. Multivariate analysis suggested that baseline XeQoLS scores, phase of treatment, and N status were associated with XeQoLS scores measured during treatment and recovery. CONCLUSIONS: Patients receiving IMPT reported the greatest xerostomia-related QoL impairment at 6 weeks on treatment, with a 49% improvement by 10 weeks after treatment; however, XeQoLS scores remained above baseline after 2 years. As we aim to establish the value of IMPT in oropharyngeal tumors to de-intensify treatment over conventional therapy, these data help inform discussions about xerostomia-related quality of life for patients with oropharyngeal cancer treated with IMPT.

A two-phase kitchen waste (KW) fermentation was proposed in the current study to enhance medium-chain fatty acids (MCFAs) production from kitchen waste. In particular, effect of acetate to butyrate ratio (ABR) on MCFAs production was investigated which can be regulated by different pH and organic loading during the acidification phase. Medium ABR (1.00) was obtained when pH is 5.5 and organic loading is 20 g VS/L in FW acidification fermentation. Subsequent chain elongation fermentation demonstrated that the highest yield of caproate 9.67 g/L with selectivity of 79 %, and highest ethanol conversion efficiency of 1.11 was achieved in medium ABR system. Microbial community study showed that medium ABR significantly enrich the functional bacteria especially Clostridium kluyveri. The study provides a new method for chain elongation enhancement without addition of other additives in kitchen waste fermentation system and gives a guide for the regulation of the short-chain fatty acids distribution in its acidification phase.

Eight new iridoids, jatavaleridoids A-H (1-8), were isolated from the roots and rhizomes of Valeriana jatamansi. Their structures and absolute configurations were elucidated based on NMR and HRESIMS spectroscopic data, as well as quantum chemical calculation. Structurally, compounds 1-5 and 8 were rare iridoids with long-chain fatty acid esters at C-10. In addition, compound 7 showed cytotoxicity, while compounds 1 and 2 exhibited inhibition on NO production.

The loess areas cover about 6% of China's land and they are thought to have a high likelihood of hosting valuable mineral resources. General geochemical exploration methods are restricted in this region due to the thick loess overburden. Here, we used geogas prospecting, which has been uniquely developed in China, to test its ability to delineate buried deposits at Shenjiayao gold deposit. Two different media: 5% ultrapure aqua regia and polyurethane foam, were used to sample the geogas in the soil. Based on concentrations and precision in our experiment, the polyfoam seemed to out-perform the aqua regia. To investigate how the anomalies formed, a special carrier was used to sample original substances in the geogas. Nanoscale gold-bearing particles were found both in the geogas, supporting the hypothesis that metallic nanoparticles released from orebodies and altered rocks during weathering process can be transported towards the surface. Besides the evidence of nanoparticles, correlations of elements in ores and geogas indicated the close connection between them. Therefore, our field experiment showed geogas prospecting can be effective in exploration for buried mineral resources.

This study aimed to develop a noodle with slow digestibility by adding pullulanase-treated wheat flour (PF). PF was prepared from normal wheat flour (NF) by pullulanase treatment, then its characteristics were compared with NF. Varying proportions (0%, 3%, 6%, 9%, 12% and 15%) of PF were substituted for NF to produce white salted noodles (WSN). The rheological, digestive, cooking, color and textural properties of WSN were evaluated. This showed that the amylose content of PF (83 wt%, total starch) was 62% higher than that of NF. After pullulanase treatment, the pasting temperature increased from 62.7 to 75.0 °C and the crystal structure of the starch changed from a mixture of A- and V-types to one of B- and V-types. Microstructure graphs showed that the structure of PF was more compact than that of NF. PF substitution produced noodles of acceptable quality with increased water absorption, cooking loss, L* value, hardness, and resilience and decreased cooking yield compared with the control (100% NF). In vitro digestibility tests showed that k (the kinetic constant) for cooked WSN decreased from 0.405 to 0.168 as substitution levels of PF increased from 0% to 15%, indicating that PF still exhibited slow digestibility after cooking.

Purpose To compare ototoxicity rates between medulloblastoma patients treated with protons vs. photons. Materials and methods The study included 84 children diagnosed with medulloblastoma treated with either passively scattered protons (n = 38) or photons (n = 46). Patients underwent maximal safe resection followed by craniospinal irradiation, posterior fossa and/or tumor bed boost and chemotherapy according to one of 3 multi-institutional trials. Median audiogram follow-up was 56 months for protons and 66 months for photons. Results Mean cochlear dose (Dmc) was lower in patients treated with protons for both standard (p Conclusions While cochlear doses were lower in the proton group, patients treated with either protons or photons had similar Grade 3 and 4 ototoxicity rates.

Background We previously reported a novel tumor-associated antigen with a molecular weight of approximately 48 kDa that was a fragment derived from human DNA-topoisomerase I. The aim of this study is to further investigate the clinical significance of the autoantibody in patients with non-small cell lung cancer (NSCLC). Methods We determined serum levels of the autoantibody in 127 NSCLC patients, 127 age-, sex-, and smoking history–matched healthy control subjects, and 38 patients with pulmonary benign tumors by using a specific enzyme linked immunosorbent assay for the autoantibody. We then statistically evaluated its clinical application value. Results Serum levels of the autoantibody in NSCLC patients were significantly higher than in healthy control subjects and patients with benign tumors ( p = 0.001). The percentage of sera with a positive level of the autoantibody was 71.8%, 65.6%, 41.9%, and 48.0% in stages I, II, III, and IV of the cancer, respectively ( p = 0.049). The area under the receiver-operating characteristics curve was 0.971 (95% confidence interval: 0.953 to 0988) for healthy controls and patients with benign tumors versus early stage NSCLC patients. Moreover, the overall survival rate of the patients in stages I, II, and IV with negative levels of the autoantibody was significantly lower than that of patients with positive levels of the autoantibody ( p = 0.013, 0.023, and 0.047 for stages I, II, and IV, respectively). Conclusions Our results indicate that the autoantibody can be used as a novel biomarker for the early diagnosis and prognosis of NSCLC.

Heterogeneous catalysts have been widely used for chemical transformations and offer easy product separation in addition to their high activity. Iron is an earth-abundant metal, but it has not been studied thoroughly as heterogeneous catalysts for organic reactions. In this work, supported iron catalysts were synthesized via loading FeCl3 onto a mesoporous silica SBA-15. These catalysts were highly active for Michael addition reactions, a synthetic pathway for forming C C bonds that is typically achieved by homogeneous catalysts. Our studies show that for the supported iron catalysts, larger pore sizes of the silica resulting from the loading of iron and the oxidation state of iron being Fe(III) are essential for the high reaction rates. Notably, the catalysts show stability against leaching, regardless the presence or absence of a dendrimer as an additional stabilizing agent. The catalysts could be used for at least three runs without the loss of activity. The successful Michael addition reactions of indole or 2-methylindole and different α,β-unsaturated ketones corroborate the synthetic scope of the catalysts. These results show promises of using supported iron catalysts as inexpensive and effective alternatives for the formation of C C bonds.

A novel approach for laser pulse reshaping with spectral scanning filtering based on Optical Kerr effect is proposed. The physical reshaping schematic is revealed and analyzed theoretically for the F-P interference filter in combination with an optical Kerr medium. The effects of the relative time-delays between pump and signal, the pump deviations and chirp errors on the reshaping performance have been investigated and discussed. Numerical simulations show that precise controlling parameters is required to better reshaping properties end. A flat top pulse with the central wavelength of 800 nm, pulse duration 0.1 ns is reshaped from a first order Gaussian chirped signal pulse. Furthermore, a flat top pulse is reshaped to parabolic shape, which demonstrated the flexibility of this reshaping approach.

The Casparian strip, a barrier to the apoplastic movement of solutes from the cortex to the stele, is essential for the exclusion of salts, selective nutrient uptake, and many other processes. To date, extensive studies have focused on the physiological functions of endodermal Casparian strips. However, the chemical deposition nature of Casparian strips, as well as its relevance with respect to diffusion barrier functions, remains to be further elucidated. Here, we revealed three developmental stages of Casparian strips in maize primary roots using a traditional fluorescent staining method. Apoplastic permeability tests demonstrated that the barrier function of Casparian strips is largely related to their developmental stage and the pattern of lignin and suberin deposits. Fourier transform infrared (FTIR) analysis showed that the Casparian strips from the roots exhibited significant absorption bands characteristic of lignin and suberin, implying that the Casparian strips in maize primary roots consist largely of lignin and suberin. Furthermore, we developed a new method for label-free, in vivo structural, and biochemical analysis of Casparian strips based on stimulated Raman scattering (SRS) microscopy. Using SRS microscopy, we found that lignin and suberin accumulate simultaneously during the Casparian strip formation process. Based on these results, we propose a potential application of SRS for the chemical composition analysis of plant Casparian strips in situ.

Convulsive status epilepticus (CSE) is a neurological disease with contraction and extension of limbs, leading to damage of hippocampus and cognition. This study aimed to explore the effects of dexmedetomidine (DEX) on the cognitive function and neuroinflammation in CSE rats. All rats were divided into control group, CSE group and DEX group. Morris water maze test was used to measure cognitive function. Acute hippocampal slices were made to detect long-term potentiation (LTP). Immunohistochemistry was used to determine the expression of α7-nicotinic acetylcholine receptor (α7-nAChR) and interleukin-1β (IL-1β). Enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of IL-1β, tumor necrosis factor-α (TNF-α), S-100β and brain-derived neurotrophic factor (BDNF). Our results showed that DEX improved the memory damage caused by CSE. DEX reduced seizure severity and increased the amplitudes and sustainable time of LTP, and also inhibited the hippocampal expression of α7-nAChR and IL-1β in CSE rats. DEX treatment decreased serum IL-1β, TNF-α and S-100β levels and increased BDNF levels. The effects of DEX on seizure severity and LTP could be simulated by nicotine or attenuated by concurrent α-bungarotoxin (α-BGT) treatment. In conclusions, DEX significantly improved spatial cognitive dysfunction, reduced seizure severity and increased LTP in CSE rats. Improvements by DEX were closely related to enhancement of cholinergic anti-inflammatory pathway.

Cell death is essential for cancer, which can be induced through multiple mechanisms. Ferroptosis, a newly emerging form of non-apoptotic cell death, involves the generation of iron-dependent reactive oxygen species (ROS). In this study, we designed and synthesized two artesunate (ART) conjugated phosphorescent rhenium(I) complexes (Re(I)-ART conjugates), [Re(N^N)(CO)3(PyCH2OART)](PF6) (Re-ART-1 and Re-ART-2) (Py = pyridine, N^N = 1,10-phenanthroline (phen, in Re-ART-1) and 4,7-diphenyl-1,10-phenanthroline (DIP, in Re-ART-2)) that can specifically locate in the mitochondria of human cervical carcinoma (HeLa). Mechanism studies show that Re-ART-1 and Re-ART-2 exhibit high cytotoxicity against cancer cells lines and can induce both apoptosis and ferroptosis in HeLa cells through mitochondrial damage, caspase cascade, glutathione (GSH) depletion, glutathione peroxidase 4 (GPX4) inactivation and lipid peroxidation accumulation. As a result, this work presents the rational design of Re(I)-ART conjugates as a promising strategy to induce both apoptosis and ferroptosis and improve therapeutic efficiency of cancer treatment.

Sedimentary basins in the arid areas of northern China have great potential to aid the discovery of new sandstone-type uranium deposits. A fine-grained (

The conversion of agricultural biomass into hydrochar has enormous potential to improve soil quality. In particular, hydrochar particles introduced into the natural environment readily bind environmental pollutants. The interaction of hydrochar and pollutants will, however, be impacted by long term natural ageing in the earth surface. The adsorption performance and the associated mechanisms that could be affected by physical or chemical ageing are not yet fully understood. To elucidate the influence of different types ageing on the physicochemical properties and sorption capacity of hydrochar, we systematically characterized the elemental composition, specific surface area, total organic carbon, and functional groups of fresh and aged hydrochar. Norfloxacin (NOR), a typical antibiotic as a model in this study, was used for the sorption performance of different aged hydrochars in the presence or absence of Cu2+. The various artificial accelerated ageing methods have been employed such as H2O2 oxidation, HNO3/H2SO4 acidification, high temperature, and freeze-thaw cycles. The results showed that ageing could increase hydrochar polarity and surface functional groups, which both increased NOR hydrophobic partition and H-bonding interaction on hydrochars. The chemical ageing largely increased the abundance of CO than physical ageing. H-bonding dominated NOR sorption on hydrochars after acidification, high temperature, and freeze-thaw cycles. The hydrophobic partition was the main sorption mechanism of NOR on oxidative aged hydrochars. The coexisting Cu2+ inhibited NOR sorption on most aged hydrochars (acidification, high temperature, and freeze-thaw cycles), whereas specially for oxidative ageing, Cu2+ increased hydrophobic sorption sites on hydrochars surface and enhanced the sorption capacity for NOR. The results from this study are likely to reveal the mechanisms of pollutant adsorption on hydrochars and their different susceptibilities under various ageing environment, suggesting us to comprehensively consider the reciprocal effects of natural ageing and coexisting pollutants on a long-term use of hydrochar in the field.

Summary Background Evidence from retrospective studies suggests that disease progression after first-line chemotherapy for metastatic non-small-cell lung cancer (NSCLC) occurs most often at sites of disease known to exist at baseline. However, the potential effect of aggressive local consolidative therapy for patients with oligometastatic NSCLC is unknown. We aimed to assess the effect of local consolidative therapy on progression-free survival. Methods In this multicentre, randomised, controlled, phase 2 study, eligible patients from three hospitals had histological confirmation of stage IV NSCLC, three or fewer metastatic disease lesions after first-line systemic therapy, an Eastern Cooperative Oncology Group performance status score of 2 or less, had received standard first-line systemic therapy, and had no disease progression before randomisation. First-line therapy was four or more cycles of platinum doublet therapy or 3 or more months of EGFR or ALK inhibitors for patients with EGFR mutations or ALK rearrangements, respectively. Patients were randomly assigned (1:1) to either local consolidative therapy ([chemo]radiotherapy or resection of all lesions) with or without subsequent maintenance treatment or to maintenance treatment alone, which could be observation only. Maintenance treatment was recommended based on a list of approved regimens, and observation was defined as close surveillance without cytotoxic treatment. Randomisation was not masked and was balanced dynamically on five factors: number of metastases, response to initial therapy, CNS metastases, intrathoracic nodal status, and EGFR and ALK status. The primary endpoint was progression-free survival analysed in all patients who were treated and had at least one post-baseline imaging assessment. The study is ongoing but not recruiting participants. This study is registered with ClinicalTrials.gov, number NCT01725165. Findings Between Nov 28, 2012, and Jan 19, 2016, 74 patients were enrolled either during or at the completion of first-line systemic therapy. The study was terminated early after randomisation of 49 patients (25 in the local consolidative therapy group and 24 in the maintenance treatment group) as part of the annual analyses done by the Data Safety Monitoring Committee of all randomised trials at MD Anderson Cancer Center, and before a planned interim analysis of 44 events. At a median follow-up time for all randomised patients of 12·39 months (IQR 5·52–20·30), the median progression-free survival in the local consolidative therapy group was 11·9 months (90% CI 5·7–20·9) versus 3·9 months (2·3–6·6) in the maintenance treatment group (hazard ratio 0·35 [90% CI 0·18–0·66], log-rank p=0·0054). Adverse events were similar between groups, with no grade 4 adverse events or deaths due to treatment. Grade 3 adverse events in the maintenance therapy group were fatigue (n=1) and anaemia (n=1) and in the local consolidative therapy group were oesophagitis (n=2), anaemia (n=1), pneumothorax (n=1), and abdominal pain (n=1, unlikely related). Interpretation Local consolidative therapy with or without maintenance therapy for patients with three or fewer metastases from NSCLC that did not progress after initial systemic therapy improved progression-free survival compared with maintenance therapy alone. These findings suggest that aggressive local therapy should be further explored in phase 3 trials as a standard treatment option in this clinical scenario. Funding MD Anderson Lung Cancer Priority Fund, MD Anderson Cancer Center Moon Shot Initiative, and Cancer Center Support (Core), National Cancer Institute, National Institutes of Health.

Two non-chiral copper(II) complexes equipped with bis(β-cyclodextrin)s (bisCDs) were explored as hydrolase models for the enantioselective hydrolysis of two pairs of alkyl chain-possessing amino acid ester enantiomers. The two bisCD complexes are pyridine-linked with different CD cavity orientations, denoted as CuL1 (L1 = 2,6-bis(6-mono-amino-β-cyclodextrin-methyl)-pyridine) and CuL2 (L2 = 2,6-bis(3-mono-amino-β-cyclodextrin-methyl)-pyridine). Kinetic studies indicated that the “back-to-back” bisCD complex CuL1 showed higher catalytic efficiency and more pronounced enantioselectivity for all substrates than the “face-to-face” bisCD complex CuL2. Overall preference of l -isomers was observed for both complexes. In the presence of CuL1, the formation of catalyst-substrate Michaelis complexes during the hydrolysis was demonstrated by saturation kinetic study and Electrospray ionization mass spectrometry (ESI–MS) analysis. Enantiomer selectivity (vmaxL/vmaxD) value for N-Boc-N'-Boc-Lysine 4-nitrophenyl esters (Boc-Lys(Boc)-ONp), the longer alkyl-chain analogs, is twice of that for N-Boc-Alanine 4-nitrophenyl esters (Boc-Ala-ONp). The enantioselective hydrolysis of Boc-Lys(Boc)-ONp promoted by CuL1 was confirmed by chiral high-performance liquid chromatography (HPLC) analysis. The participation of CD cavities during enantioselective hydrolysis was investigated through inhibition assay. The enantioselectivity in hydrolyzing different amino acid esters promoted by CuL1 was compared. The mechanism involved in the cooperation of two adjacent CD cavities of bisCD was proposed.

Introduction Clinical cohort studies suggest that mild cognitive impairment (MCI) is common in early Parkinson's disease (PD). The objectives of this paper were to describe cognitive function in a large clinical trial of early treated PD patients at baseline and over time using two brief cognitive screening tests. Methods In total 1741 participants were enrolled in the NINDS Exploratory Trials in Parkinson's disease (NET-PD) Long-term Study-1 (LS-1). The Symbol Digit Modalities Test (SDMT) was collected annually. The SCales for Outcomes in PArkinson's disease-COGnition (SCOPA-COG) was collected at baseline and at year 5. The trial was stopped early based on a planned interim analysis after half the cohort completed 5 years of follow-up. The median length of follow-up was 4 years (range 3–6 years). Predictors of cognitive change were examined using cross sectional (baseline) and longitudinal multivariable linear regression. Results The mean (SD) change from baseline to 5 years was −1.9 (5.1) for the SCOPA-COG and −2.1 (11.1) for the SDMT. Age and baseline UPDRS motor scores were associated with a more rapid decline in SDMT scores and 5 year SCOPA-COG scores. Male gender was associated with more rapid decline in SDMT. Self-reported income was a novel predictor of baseline cognitive function, even adjusted for educational status, although not significantly associated with change over time. Conclusion This large prospective cohort study demonstrated mild cognitive decline in early treated Parkinson's disease. The study identified income level as a novel predictor of cognitive function.

Background:Bipolar disorder (BD) is difficult to diagnose in the early stages of the illness, with the most frequent misdiagnosis being major depressive disorder (MDD). We aimed to use a regional homogeneity (ReHo) approach with resting-state functional magnetic resonance imaging (rs-fMRI) to investigate the features of spontaneous brain activity in MDD patients screening positive on the 32-item Hypomania Checklist (HCL-32).Methods:Nineteen MDD patients screening positive (HCL-32(+); 9 males; 24.9 ± 5.7 years) and 18 patients screening negative (HCL-32(-); 9 males; 27.1 ± 6.7 years), together with 24 healthy controls (HC; 11 males; 26.4 ± 3.9 years) were studied. ReHo maps were compared and an receiver operating characteristic (ROC) analysis was conducted to confirm the utility of the identified ReHo differences in classifying the patients. Results The MDD versus HC showed different ReHo in many brain areas, especially in the frontal and parietal cortex. The HCL-32(+) versus HCL-32(-) showed significant increase of ReHo in the right medial superior frontal cortex, left inferior parietal cortex and middle/inferior temporal cortex, and decrease of ReHo in the left postcentral cortex and cerebellum. ROC analysis showed good sensitivity and specificity for distinguishing these two subgroups of MDD. Limitations Recruited patients were all on antidepressants and standard mania rating scales were not used to assess their hypomanic symptoms. Conclusions:The rs-fMRI measurement of ReHo in distributed brain regions may be putative biomarkers which could differentiate subthreshold BD from MDD.

At present, increasingly more proton medical facilities have been established globally for better curative effect and less side effect in tumor treatment. Compared with electron and photon, proton delivers more energy and dose at its end of range (Bragg peak), and has less lateral scattering for its much larger mass. However, proton is much easier to produce neutron and induced radioactivity, which makes radiation protection for proton accelerators more difficult than for electron accelerators. This study focuses on the problem of patient-induced radioactivity during proton treatment, which has been ignored for years. However, we confirmed it is a vital factor for radiation protection to both patient escort and positioning technician, by FLUKA’s simulation and activation formula calculation of Hengjian Proton Medical Facility (HJPMF), whose energy ranges from 130 to 230 MeV. Furthermore, new formulas for calculating the activity buildup process of periodic irradiation were derived and used to study the relationship between saturation degree and half-life of nuclides. Finally, suggestions are put forward to lessen the radiation hazard from patient-induced radioactivity.

Polyamide composite membranes are still required to promote their structure uniformity and desalination performance. Herein, a vacuum-assisted strategy was used to deal with this challenge by improving the distribution homogeneity of diamine monomer in porous substrates for typical interfacial polymerization. Laser scanning confocal microscope analyses demonstrate that the piperazine solution can be adsorbed in the microporous substrates with a very homogeneous and stable way. This uniform diamine distribution shows great advantages for synthesizing the selective layers of polyamide on the substrate surfaces via the interfacial polymerization of piperazine and trimesoyl chloride. The as-prepared polyamide layers with a circular size of 30 cm exhibit uniform structures including thickness less than 20 nm, cross-linking degree up to 100%, surface roughness lower than 20 nm and pore diameter about 0.41 nm. Therefore, the polyamide composite membranes present nanofiltration performances of ultrahigh rejection above 99.6% to Na2SO4 and high water permeability of 20 L/m2 h bar. These membranes also show a promising selectivity for NaCl/Na2SO4 up to 196, which is higher than most of the commercial and the reported nanofiltration membranes in recent years.

Background Ginseng has therapeutic potential for treating obesity and the associated gut microbiota dysbiosis. However, whether white ginseng and red ginseng, the two kinds of commonly used processed ginseng, possess different anti-obesity effects remains unknown. Purpose Anti-obesity effects of water extracts of white ginseng and red ginseng (WEWG and WERG) were compared, and the potential mechanisms were discussed. Methods Chemical profiles of WEWG and WERG were characterized by ultra-high performance liquid chromatography-tandem triple quadrupole mass spectrometry (UHPLC-QqQ-MS/MS) and high performance liquid chromatography coupled with evaporative light scattering detector (HPLC-ELSD). Anti-obesity effects of WEWG/WERG were examined by determining fat accumulation, systemic inflammation, enteric metabolic disorders and gut microbiota dysbiosis in high-fat diet (HFD)-fed obese mice. Results Both WEWG and WERG exerted anti-obesity effects, with WEWG stronger than WERG. Compared to WERG, WEWG contained less contents of carbohydrates (polysaccharides, oligosaccharides, free monosaccharides) and ginsenosides, but chemical structures or compositions of these components in WEWG were characteristic, i.e. narrower molecular weight distribution and higher molar ratios of glucose residues of polysaccharides; higher content ratios of oligosaccharides DP2–3 (di-/tri-saccharides)-to-oligosaccharides DP4–7 (tetra-/penta-/hexa-/hepta-saccharides), sucrose-to-melibiose, maltose-to-trehalose and high-polar-to-low-polar ginsenosides. WEWG better ameliorated fat accumulation, enteric metabolic disorders and gut microbiota dysbiosis in HFD-fed obese mice than WERG. Conclusion The stronger anti-obesity effect of white ginseng appears to correlate with differences in its chemical profile as compared to red ginseng. The carbohydrates and ginsenosides in WEWG potentially present more structural and compositional specificity to the obesity-associated gut bacteria, allowing more beneficial effects of WEWG on the gut microbiota dysbiosis. This consequently better alleviates the enteric metabolic disorders and systemic inflammation, thereby contributing to the stronger anti-obesity effect of WEWG as compared to WERG.

The phytohormone auxin plays a central role in coordinating plant growth and development. GH3 is one of the three gene families that respond rapidly during auxin stimulation. Here, we report the identification and characterization of the GH3 gene family in maize. A total of 12 GH3 genes were identified, which are not evenly distributed over the 10 maize chromosomes. Maize GH3 protein sequences share a conserved domain which occupies nearly the entire protein. Diversified cis-elements were found in promoters of maize GH3 genes. In this study, the 12 maize GH3 proteins were primarily classified into two phylogenetic groups, similar to the 13 rice GH3 proteins, while 9 of the 19 Arabidopsis GH3 proteins were observed in the third phylogenetic group. Microarray analysis showed that expression of maize GH3 genes is temporally and spatially modulated. Additionally, maize GH3 genes displayed variable changes at transcript level upon pathogen infection. Results presented here provide insight into the diversification and evolution of GH3 proteins, and lay a foundation for the functional characterization of these GH3 genes in future, especially for elucidating the mechanisms of GH3-mediated pathogenesis.