MYC Recruits SPT5 to RNA Polymerase II to Promote Processive Transcription Elongation.

The MYC oncoprotein binds to promoter-proximal regions of virtually all transcribed genes and enhances RNA polymerase II (Pol II) function, but its precise mode of action is poorly understood. Using mass spectrometry of both MYC and Pol II complexes, we show here that MYC controls the assembly of Pol II with a small set of transcription elongation factors that includes SPT5, a subunit of the elongation factor DSIF. MYC directly binds SPT5, recruits SPT5 to promoters, and enables the CDK7-dependent transfer of SPT5 onto Pol II. Consistent with known functions of SPT5, MYC is required for fast and processive transcription elongation. Intriguingly, the high levels of MYC that are expressed in tumors sequester SPT5 into non-functional complexes, thereby decreasing the expression of growth-suppressive genes. Altogether, these results argue that MYC controls the productive assembly of processive Pol II elongation complexes and provide insight into how oncogenic levels of MYC permit uncontrolled cellular growth.

Author Correction: Chimeric peptidomimetic antibiotics against Gram-negative bacteria.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Chimeric peptidomimetic antibiotics against Gram-negative bacteria.

There is an urgent need for new antibiotics against Gram-negative pathogens that are resistant to carbapenem and third-generation cephalosporins, against which antibiotics of last resort have lost most of their efficacy. Here we describe a class of synthetic antibiotics inspired by scaffolds derived from natural products. These chimeric antibiotics contain a ß-hairpin peptide macrocycle linked to the macrocycle found in the polymyxin and colistin family of natural products. They are bactericidal and have a mechanism of action that involves binding to both lipopolysaccharide and the main component (BamA) of the ß-barrel folding complex (BAM) that is required for the folding and insertion of ß-barrel proteins into the outer membrane of Gram-negative bacteria. Extensively optimized derivatives show potent activity against multidrug-resistant pathogens, including all of the Gram-negative members of the ESKAPE pathogens1. These derivatives also show favourable drug properties and overcome colistin resistance, both in vitro and in vivo. The lead candidate is currently in preclinical toxicology studies that-if successful-will allow progress into clinical studies that have the potential to address life-threatening infections by the Gram-negative pathogens, and thus to resolve a considerable unmet medical need.

Study on the Ameliorative Effect of Icariin Mediating NO/cGMP/PKGI Signalling Pathway in Alzheimer's Disease.

Objective: To investigate the effect of icariin (ICA) on cognitive function and NO/cGMP/PKGI signaling pathway in mice with Alzheimer's disease (AD). Methods: Wild-type C57BL/6 mice were used as the Control group, and APP/PS1 double transgenic mice were used to establish the AD model. The mice were randomly divided into AD group, AD+L-icariin group (10 mg/kg), and AD+H-icariin group (40 mg/kg), with 10 mice in each group. Water maze and Y-maze tests were used to evaluate the learning and memory abilities of mice. ELISA was used to measure the levels of serum Aß and cGMP. Tunel staining was used to determine the apoptosis of neurons in the hippocampus. Immunohistochemistry was used to measure the expression of Brdu, Dcx, and NeuN in the hippocampus. The protein expressions of iNOS, sGC, PKGI, Caspase3, Bax, and Bcl-2 in brain tissue were determined by Western blot. Results: Compared with the control group, the learning and memory ability of the AD group was significantly decreased, the serum levels of Aß and cGMP were increased, the neuronal apoptosis was increased, the contents of Brdu, Dcx and NeuN were decreased, the expression of iNOS, sGC, PKGI, Caspase-3 and Bax proteins was increased, and the expression of Bcl-2 protein was decreased (P < .05). Compared with the AD group, the AD mice treated with icariin (40mg/kg) showed improved learning and memory abilities, decreased serum Aß and cGMP contents, decreased neuronal apoptosis, increased Brdu, Dcx, and NeuN contents, and decreased iNOS, sGC, PKGI, Caspase-3, and Bax protein expressions. The expression of Bcl-2 protein was increased (P < .05). Conclusion: Icariin improves AD in mice by activating the NO/cGMP/PKGI signaling pathway.

A cross-sectional study on Chinese oncology nurses' knowledge of bone health among cancer patients.

OBJECTIVE: To understand the knowledge status, obstacle factors, and management confidence of oncology nurses on the bone health of cancer patients, and in addition to provide reference for establishing bone health knowledge training system for oncology nurses and guiding them to manage bone health of cancer patients. METHODS: A total of 602 nurses engaged in oncology nursing in 6 hospitals in Hebei Province were selected by cluster sampling, and an online anonymous survey was conducted by sending questionnaires to oncology nurses from the Hebei Cancer Prevention and Control Association. The questionnaire was developed by the study team. There are 4 parts, namely general information, nurses' role and job responsibilities, knowledge of skeletal-related events (SREs) and cancer treatment-induced bone loss (CTIBL), and understanding and confidence in bone health management, for a total of 33 questions. RESULTS: Thirty-seven percent of oncology nurses received training on bone health and other related contents; 40.48% of oncology nurses used domestic and foreign guidelines when managing patients with bone metastases or CTIBL. Only approximately one-third of oncology nurses had confidence in managing the side effects of bone metastases and bone modification drugs and identifying patients at risk of CTIBL and fracture; only 33.04% of oncology nurses believed that weight-bearing exercise can prevent bone loss; less than 50% of oncology nurses believed that aromatase inhibitor therapy, ovarian suppression therapy, androgen deprivation therapy, and low body weight were risk factors for pathological fractures. The reasons that hindered oncology nurses from optimizing the management of patients with bone metastases and understanding the preventive measures and risk factors for bone loss mainly included lack of relevant knowledge training, lack of understanding of effective intervention measures, and lack of training and professionalism of specialized nurses, including insufficient development time and guidelines for clinical nursing practice. CONCLUSION: Managers must continuously improve the training system of oncology nurses, enrich the content of training pertaining to bone health for cancer patients, formulate clinical nursing practice guidelines, and give oncology nurses more time for professional development.

Molecular cloning, expression analysis of the IgT gene and detection of IgT+ B cells in the half-smooth tongue sole (Cynoglossus semilaevis).

IgT is a specific Ig isotype in teleosts, which plays extremely important roles in the mucosal immunity of fish. In the present study, the membrane-bound and secretory IgT of the half-smooth tongue sole (Cynoglossus semilaevis) were identified for the first time. The V-D-J-C structure of two forms of csIgT are translated by the same Cτ gene, and the secretory tail and transmembrane domain were encoded through alternative splicing at the 3' end of the Cτ4. The CH regions of csIgT had high similarity with that of other flatfish (P. olivaceus and S. maximus). In healthy C. semilaevis, sIgT and mIgT were mainly expressed in mucus related tissues such as skin, intestine and gill. The transcript levels of sIgT and mIgT mRNA showed a significant induction in the immune-related tissues upon Vibrio Harveyi infection. A polyclonal rabbit anti-csIgT was successfully prepared using the csIgT heavy chain recombinant protein. Using this antibody, we detected the native IgT with the molecular mass at 220 kDa in skin total protein under non-reducing SDS-PAGE condition. Immunofluorescence analysis indicated that IgT+ B lymphocytes were intensively located in the skin, gill, intestine, and head kidney of C. semilaevis. These results suggest that IgT may participate in the immune response of C. semilaevis, which will facilitate the investigations of the immunoglobulins of marine fish.

Phenolic compounds from the leaves of Crataegus pinnatifida Bge. var. major N.E.Br. And their lipid-lowering effects.

A phytochemical study on the leaves of Crataegus pinnatifida Bge. var. major N.E.Br. was carried out, which finally led to the isolation of nineteen phenolic compounds (1-19). The structures of all compounds were established mainly by NMR and MS spectroscopic analysis as well as the necessary ECD experimental evidence, of which compounds 1-4 (crataegunins A-D) were identified as new phenylpropanoid-substituted epicatechins. HepG2 cells were induced by oleic acid and palmitic acid to establish the model of lipid metabolism disorder. All isolated compounds were used to intervene in the model, and the contents of triglyceride (TG) and total cholesterol (TC) were detected. Compound 2 could significantly reduce the content of TG, while compounds 2 and 11 both have good activity in reducing TC content.

Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) and Treadmill Training on Recovery of Motor Function in a Rat Model of Partial Spinal Cord Injury.

BACKGROUND This study aimed to investigate the effects of repetitive transcranial magnetic stimulation (rTMS) and treadmill training (TT) on motor function recovery in rats with partial spinal cord injury (SCI). MATERIAL AND METHODS Sixty rats with moderate partial SCI at the 9th thoracic vertebral level induced by a Louisville Injury System Apparatus impactor were randomly allocated to 5 groups: Sham surgery (Intact); Sham rTMS without TT (S-rTMS/Non-TT); Sham rTMS with TT (S-rTMS/TT); rTMS without TT (rTMS/Non-TT); and rTMS with TT (rTMS/TT). Interventions commenced 8 days after SCI and continued for 8 weeks. Outcomes studied were Basso, Beattie, and Bresnahan locomotor scale scores, grid walking test, and biochemical analysis of the brain-derived neurotrophic factor (BDNF), synapsin I (SYN), and postsynaptic density protein-95 (PSD-95) in the motor cortex and spinal cord. RESULTS The rTMS/TT contributed to greater Basso, Beattie, and Bresnahan scores compared with the S-rTMS/Non-TT (P<0.01), S-rTMS/TT (P<0.05), and rTMS/Non-TT (P<0.05), and showed obviously reduced numbers of foot drops compared with the S-rTMS/Non-TT (P<0.05). The rTMS/TT significantly increased the expressions of BDNF, SYN, and PSD-95 compared with the S-rTMS/Non-TT, both in the motor cortex (P<0.01, P<0.01, P<0.001, respectively) and spinal cord (P<0.001, P<0.01, P<0.05, respectively). CONCLUSIONS In a modified rat model of SCI, combined rTMS with TT improved motor function, indicating that this combined approach promoted adaptive neuroplasticity between the motor cortex and the spinal cord. A combined app roach to improving motor function following SCI requires further evaluation to determine the possible clinical applications.

[Terpenoids from leaves of Chinese hawthorn].

Fifteen compounds were isolated from the 70% EtOH extract of leaves of Chinese hawthorn(Crataegus pinnatifida var. major) by various purification steps, and their structures were determined as 2α,3α,12ß,19α,-tetrahydroxyursan-13ß,28-olide(1),euscaphic acid(2), tormentic acid(3), ursolic acid(4), pomolic acid(5), corosolic acid(6), maslinic acid(7), linalyl rutinoside(8),(Z)-3-hexenyl ß-D-glucoside(9),(3S, 6S)-cis-linalool-3,7-oxide-ß-D-glucopyranoside(10), pisumionoside(11), icariside B6(12), byzantionoside B(13),(6R,7E,9R)-9-Hydroxy-4,7-megastigmadien-3-one 9-O-ß-D-glucopyranoside(14) and(6S,7E,9R)-6,9-dihydroxy-4,7-megastigmadien-3-one 9-O-ß-D-glucopyranoside(15) mainly based on the mass spectrum(MS) and nuclear magnetic resonance(NMR) spectroscopic techniques, of which compound 1 was a new pentacyclic triterpene, and compounds 2, 5, 6, 8, 10, 13 and 15 were isolated form this plant for the first time.

Bacillus lacisalsi sp. nov., a moderately haloalkaliphilic bacterium isolated from a saline-alkaline lake.

An alkaliphilic and moderately halophilic strain, designated YSP-3T, characterised by optimal growth at pH 9.0 and at 8.0% (w/v) NaCl, was isolated from Yangshapao Lake, Jilin Province, China. Cells of this strain is Gram-positive, straight rods and form a central or sub-terminal ellipsoidal endospore. Phylogenetic analysis based on 16S rRNA gene sequences indicated that it was grouped in the genus Bacillus with Bacillus aurantiacus K1-5T and Bacillus populi FJAT-45347T as the close relative (97.5 and 97.2% 16S rRNA gene sequence similarity, respectively). Genomic relatedness between strain YSP-3T and its close relative was evaluated using average nucleotide identity, digital DNA-DNA hybridization and average amino acid identity with the values of 70.3-85.1%, 19.7-20.1% and 71.5-71.6%, respectively. Comparative genomics analysis showed that strain YSP-3T has distinct amino acid bias and significantly differences from foreign invasion events during evolution relative to the reference strains. Cell-wall peptidoglycan contains meso-diaminopimelic acid. The predominant polar lipids are phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol. The predominant quinone is menaquinone-7. The major fatty acids of strain YSP-3T are anteiso-C15:0, iso-C15:0, iso-C16:0, anteiso-C17:0 and Iso-C14:0. DNA G + C content of strain YSP-3T is 48.3 mol%. Based on genomics analysis, physiological, biochemical and chemotaxonomic data, strain YSP-3T represent a novel species, for which the name Bacillus lacisalsi sp. nov. is proposed. The type strain is YSP-3T (  = ACCC 60365T = KCTC 33934T).

cDNA cloning, characterization, and expression analysis of the Rac1 and Rac2 genes from Cynoglossus semilaevis.

Rac1 and Rac2, belonging to the small Rho GTPase family, play an important role during the immune responses. In this study, a Rac1 homolog (CsRac1) and a Rac2 homolog (CsRac2) were cloned from the Cynoglossus semilaevis. The full-length of CsRac1 and CsRac2 cDNA was 1219 bp and 1047 bp, respectively. Both CsRac1 and CsRac2 contain a 579 bp open reading frame (ORF) which encoding a 192 amino acids putative protein. The predicted molecular weight of CsRac1 and CsRac2 was 21.41 kDa and 21.35 kDa, and their theoretical pI was 8.50 and 7.91, respectively. Sequence analysis showed that the conserved RHO domain was detected both from amino acid of CsRac1 and CsRac2. Homologous analysis showed that CsRac1 and CsRac2 share high conservation with other counterparts from different species. The CsRac1 and CsRac2 transcript showed wide tissue distribution, in which CsRac1 and CsRac2 exhibit the highest expression level in liver and gill, respectively. The expression level of CsRac1 and CsRac2 fluctuated in the liver and gill tissues at different time points after challenged by Vibrio harveyi. Specifically, CsRac1 and CsRac2 were significantly up-regulated at 48 h and 96 h post injection. Moreover, the knocking down of CsRac1 and CsRac2 in cell line (TSHKC) reduced the expression of CsPAK1, CsIL1-ß and CsTNF-α. The present data suggests that CsRac1 and CsRac2 might play important roles in the innate immunity of half-smooth tongue sole.

Salipaludibacillus keqinensis sp. nov., a moderately halophilic bacterium isolated from a saline-alkaline lake.

A novel Gram-stain positive, short rod, forming sub-terminal endospores of ellipsoidal shape, halophilic, alkaliphilic and aerobic bacterium, designated strain KQ-12T, was isolated from a saline-alkaline lake in China, and characterised by a polyphasic taxonomic approach. The isolate grew at 4-40 °C (optimum, 25 °C), at pH 8.0-10.0 (pH 9.0) and in the presence of 0-16% (w/v) NaCl (8%). 16S rRNA gene sequence similarity of KQ-12T to species in the genera Salipaludibacillus ranged from 96.6 to 98.1%. Phylogenetic trees indicated that the strain should be assigned to the genus Salipaludibacillus. The polar lipids of KQ-12T were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, and an unidentified phospholipid and its major cellular fatty acids were anteiso-C15:0, anteiso-C17:0, iso-C15:0, and C16:0. The isoprenoid quinone was MK-7. These key chemotaxonomic properties also confirmed the affiliation of the strain to the genus Salipaludibacillus. However, some physiological, biochemical properties, low average nucleotide identity and low digital DNA-DNA hybridization relatedness values enabled the strain to be differentiated from closely related species of the genus Salipaludibacillus. Thus, KQ-12T can be classified as a novel species in the genus Salipaludibacillus, for which the name Salipaludibacillus keqinensis sp. nov. is proposed. The type strain is KQ-12T ( =  ACCC 60430T   =  KCTC 33935T).

3'-O-Methylorobol Inhibits the Voltage-Gated Sodium Channel Nav1.7 with Anti-Itch Efficacy in A Histamine-Dependent Itch Mouse Model.

An itch is a clinical complication that affects millions of patients. However, few treatment options are available. The voltage-gated sodium channel Nav1.7 is predominantly expressed in peripheral sensory neurons and is responsible for the rising phase of action potentials, thereby mediating nociceptive conduction. A gain-of-function mutation of Nav1.7 results in the hyperexcitability of sensory neurons and causes the inherited paroxysmal itch. Conversely, a monoclonal antibody that selectively inhibits Nav1.7 is able to effectively suppress the histamine-dependent itch in mice. Therefore, Nav1.7 inhibitors may possess the potential to relieve the itch. In the present study, using whole-cell voltage-clamp recordings, we demonstrated that 3'-O-methylorobol inhibited Na+ currents in Nav1.7-CHO cells and tetrodotoxin-sensitive Na+ currents in mouse dorsal root ganglion (DRG) neurons with IC50 (half-maximal inhibitory concentration) values of 3.46 and 6.60 µM, respectively. 3'-O-methylorobol also suppressed the tetrodotoxin-resistant Na+ currents in DRG neurons, though with reduced potency (~43% inhibition at 30 µM). 3'-O-methylorobol (10 µM) affected the Nav1.7 by shifting the half-maximal voltage (V1/2) of activation to a depolarizing direction by ~6.76 mV, and it shifted the V1/2 of inactivation to a hyperpolarizing direction by ~16.79 mV. An analysis of 3'-O-methylorobol activity toward an array of itch targets revealed that 3'-O-methylorobol was without effect on histamine H1 receptor, TRPV1, TRPV3, TRPV4, TRPC4 and TRPM8. The intrathecal administration of 3'-O-methylorobol significantly attenuated compound 48/80-induced histamine-dependent spontaneous scratching bouts and the expression level of c-fos in the nuclei of spinal dorsal horn neurons with a comparable efficacy to that of cyproheptadine. Our data illustrated the therapeutic potential for 3'-O-methylorobol for histamine-dependent itching, and the small molecule inhibition of Nav1.7 may represent a useful strategy to develop novel therapeutics for itching.

Massilia violaceinigra sp. nov., a novel purple-pigmented bacterium isolated from glacier permafrost.

A Gram-stain-negative, motile and rod-shaped bacterium, designated strain B2T, which can synthesize purple pigments of violacein and dexyoviolacein, was isolated from Tianshan glacier in Xinjiang, China. Phylogenetic analysis based on 16S rRNA gene sequences indicated that it was grouped in the genus Massilia with Massilia glaciei B448-2T, Massilia eurypsychrophila B528-3T and Massilia psychrophila B1555-1T as its closest relatives (98.2, 97.9 and 97.0 % 16S rRNA gene sequence similarity, respectively). Genomic relatedness between strain B2T and its closest relatives was evaluated using average nucleotide identity, digital DNA-DNA hybridization and average amino acid identity, with values of 77.93-85.08 %, 22.4-23.4 % and 71.54-72.99 %, respectively. Q-8 was the major ubiquinone. The major fatty acids (>5 %) of strain B2T were summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), C12 : 0 and summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c). The major polar lipids included phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. The DNA G+C content of strain B2T was 63.51 mol%. Based on genomic relatedness, physiological, biochemical and chemotaxonomic data, strain B2T (=CGMCC 1.6993T=DSM 19531T=KCTC 32446T) is considered to represent a novel species within the genus Massilia, for which the name Massilia violaceinigra sp. nov. is proposed.

A Novel Prediction Model for Postmolar Gestational Trophoblastic Neoplasia and Comparison With Existing Models.

OBJECTIVE: The aim of this study was to comparatively study a novel model and existing models of predicting postmolar gestational trophoblastic neoplasia (GTN). METHODS: Two hundred twenty-two patients with complete hydatidiform moles were enrolled retrospectively. A natural regression was noted in 195 patients (spontaneous regression group), whereas the remaining 27 patients entered postmolar GTN (postmolar GTN group). The upper limits of the 95% confidence interval of human chorionic gonadotropin (hCG) values and hCG regression rates were calculated aggregately from the spontaneous regression group. The 4 prediction models (weekly hCG regression curve and weekly hCG regression rate curve reported by previous studies; daily hCG regression curve and daily hCG regression rate curve pioneered by us) were then plotted. The individual hCG curve of the postmolar GTN group was plotted and compared with the prediction models, respectively. The individual hCG curve superimposing the prediction curve was considered showing an elevated risk of GTN. RESULTS: All patients with postmolar GTN were preidentified by daily hCG regression rate curve. The other 3 prediction models had a considerable rate of failure in identification. Mean diagnosis time of daily hCG regression rate curve was significantly lower (P = 0.008), with an average of 15.3 days gained compared with International Federation of Gynecology and Obstetrics criteria. Cochran Q test showed that daily hCG regression rate curve produced a significantly better performance in predicting postmolar GTN than weekly hCG regression curve (P = 0.01). CONCLUSIONS: Our data showed that daily hCG regression rate curve gives a better prediction of postmolar GTN and might potentially enhance the monitoring of patients with molar pregnancy, especially those who could not adhere to International Federation of Gynecology and Obstetrics protocols. However, this preliminary research should not change current clinical practice until further validation is carried out.

Effect of transcutaneous acupoint electrical stimulation on propofol sedation: an electroencephalogram analysis of patients undergoing pituitary adenomas resection.

BACKGROUND: Transcutaneous acupoint electrical stimulation (TAES) as a needleless acupuncture has the same effect like traditional manual acupuncture. The combination of TAES and anesthesia has been proved valid in enhancing the anesthetic effects but its mechanisms are still not clear. METHODS: In this study, we investigated the effect of TAES on anesthesia with an electroencephalogram (EEG) oscillation analysis on surgery patients anesthetized with propofol, a widely-used anesthetic in clinical practice. EEG was continuously recorded during light and deep propofol sedation (target-controlled infusion set at 1.0 and 3.0 µg/mL) in ten surgery patients with pituitary tumor excision. Each concentration of propofol was maintained for 6 min and TAES was given at 2-4 min. The changes in EEG power spectrum at different frequency bands (delta, theta, alpha, beta, and gamma) and the coherence of different EEG channels were analyzed. RESULTS: Our result showed that, after TAES application, the EEG power increased at alpha and beta bands in light sedation of propofol, but reduced at delta and beta bands in deep propofol sedation (p < 0.001). In addition, the EEG oscillation analysis showed an enhancement of synchronization at low frequencies and a decline in synchronization at high frequencies between different EEG channels in either light or deep propofol sedation. CONCLUSIONS: Our study showed evidence suggested that TAES may have different effects on propofol under light and deep sedation. TAES could enhance the sedative effect of propofol at low concentration but reduce the sedative effect of propofol at high concentration.

PtPLC, a pacifastin-related inhibitor involved in antibacterial defense and prophenoloxidase cascade of the swimming crab Portunus trituberculatus.

Pacifastin-related inhibitor is a new family of serine protease inhibitors that regulate the proteolytic cascade in multiple biological processes. Contrary to the knowledge on the structure and inhibitory mechanism of pacifastin-like members in locust, very little is known about their functions. Here, we report the inhibitory activities in relation to the structural characteristics of pacifastin light chain (PtPLC) gene identified from the swimming crab Portunus trituberculatus. The mature PtPLC and five PLD-related domains with critical residues were expressed in Escherichia coli, and assayed for their activities. The recombinant PtPLC (rPtPLC) displayed inhibitory activities against trypsin and chymotrypsin in a dose dependent manner, with a preference for trypsin. Except for rPtPLC-D4, the other four rPtPLC-related domains could inhibit at least one of serine proteases. The enzyme specificity of PtPLC domains generally corresponded to the nature of the P1 residue at the reactive site. rPtPLC was able to inhibit the growth of Gram-negative bacteria Vibrio alginolyticus and Pseudomonas aeruginosa, but not the Gram-positive bacterium and fungus tested. Further phenoloxidase (PO) assay showed the rPtPLC could depress the crab proPO system activation in vitro, and lead to 72.8% inhibition of PO activity at the concentration of 9.11 µM. It also suppressed proPO activation induced by rPtcSP and rPtSPH1. As the first functional study of the recombinant PLC protein in crustaceans, the present results together indicate that PtPLC functions in the crab immune response possibly via inhibiting bacterial growth and regulating the proPO system.

[Chemical constituents of Eucommia ulmoides].

OBJECTIVE: To study the chemical compositions of Eucommia ulmoides. METHODS: The compounds were isolated and purified from Eucommia ulmoides by silica gel column chromatography, Sephadex LH-20, MPLC packed with MCI gel and semi-preparative HPLC. The structures of these compounds were established on the basis of spectral analyses (1H-NMR, 13C-NMR and MS). RESULTS: Thirteen compounds were obtained,and their structures were identified as betulin (1), syringin (2), pervoside A (3), glucosyringic acid (4), vanillic acid-beta-glucoside (5), geniposide acid (6), aucubin (7), geniposide (8), pinoresinol-4,4'-di-O-beta-D-glucopyranoside (9), syringaresinol di-O-beta-D-glucopyranoside (10), medioresinol di-O-beta-D-glucopyranoside (11), sucrose (12), and ethyl beta-glucopyranoside (13) on the basis of physical characteristics and spectral data. CONCLUSION: Compounds 3 - 5, 12 and 13 are isolated from this plant for the first itme.

Alterations in brain functional connectivity in patients with mild cognitive impairment: A systematic review and meta-analysis of functional near-infrared spectroscopy studies.

Emerging evidences suggest that cognitive deficits in individuals with mild cognitive impairment (MCI) are associated with disruptions in brain functional connectivity (FC). This systematic review and meta-analysis aimed to comprehensively evaluate alterations in FC between MCI individuals and healthy control (HC) using functional near-infrared spectroscopy (fNIRS). Thirteen studies were included in qualitative analysis, with two studies synthesized for quantitative meta-analysis. Overall, MCI patients exhibited reduced resting-state FC, predominantly in the prefrontal, parietal, and occipital cortex. Meta-analysis of two studies revealed a significant reduction in resting-state FC from the right prefrontal to right occipital cortex (standardized mean difference [SMD] = -.56; p < .001), left prefrontal to left occipital cortex (SMD = -.68; p < .001), and right prefrontal to left occipital cortex (SMD = -.53; p < .001) in MCI patients compared to HC. During naming animal-walking task, MCI patients exhibited enhanced FC in the prefrontal, motor, and occipital cortex, whereas a decrease in FC was observed in the right prefrontal to left prefrontal cortex during calculating-walking task. In working memory tasks, MCI predominantly showed increased FC in the medial and left prefrontal cortex. However, a decreased in prefrontal FC and a shifted in distribution from the left to the right prefrontal cortex were noted in MCI patients during a verbal frequency task. In conclusion, fNIRS effectively identified abnormalities in FC between MCI and HC, indicating disrupted FC as potential markers for the early detection of MCI. Future studies should investigate the use of task- and region-specific FC alterations as a sensitive biomarker for MCI.

A convergent fabrication of pH and redox dual-responsive hybrids of mesoporous silica nanoparticles for the treatment of breast cancer.

Mesoporous silica nanoparticle (MSN), sodium hyaluronate (SH), silk fibroin (SS), and oxidized sodium carboxymethyl cellulose (O-CMC) hybrids were used to develop an intelligent drug delivery platform that may be employed for pH and redox-responsive bi-drug administration. The first drug, cytarabine (Cyt), was loaded with amino-functionalized mesoporous silica (MSN-NH2) encased by the hydrogel of cystamine (Cys) and SH cross-linked by amide bonds. Hydrophobic doxorubicin (DOX) was co-loaded with Cyt/MSN-NH2/SA in the hydrogel of SS and O-CMC in the Cyt- loaded hydrogel. Dual-responsive drug delivery may be achieved by encapsulating SS and O-CMC in a hydrogel, including Cyt/MSN-NH2/SA/DOX/SS/O-CMC, which has acyl hydrazone bonds (-HC = N) and disulfide bond (-S-S-) exchange reaction with glutathione (GSH). Compared to hydrogels encapsulating only one drug (Cyt or DOX), cell survival analysis revealed that the newly fabricated hydrogels have significantly greater chemotherapeutic efficacy. The cell proliferation of the fabricated nanoparticles was examined in MCF-7 and MDA-MB-231 cells, which indicates that the nanoparticles effectively kill the cancer cells without affecting non-cancerous cells. Further, we effectively investigated the morphological changes, and various biochemical staining methods examined nuclear fragmentation/condensation. Furthermore, the biosafety of the nanoparticles was investigated by the in vivo animal model, which reveals that they remarkably enhanced the safety profile in various organs. These outcomes demonstrated that this nanoparticle platform was a promising beneficial agent for improving breast cancer treatment.