High-Throughput Screening for Boride Superconductors.

A high-throughput screening using density functional calculations is performed to search for stable boride superconductors from the existing materials database. The workflow employs the fast frozen-phonon method as the descriptor to evaluate the superconducting properties quickly. Twenty-three stable candidates were identified during the screening. The superconductivity was obtained earlier experimentally or computationally for almost all found binary compounds. Previous studies on ternary borides are very limited. Our extensive search among ternary systems confirmed superconductivity in known systems and found several new compounds. Among these discovered superconducting ternary borides, TaMo2B2 shows the highest superconducting temperature of ∼12 K. Most predicted compounds were synthesized previously; therefore, our predictions can be examined experimentally. Our work also demonstrates that the boride systems can have diverse structural motifs that lead to superconductivity.

Design and Engineering of Hypoxia and Acidic pH Dual-Stimuli-Responsive Intelligent Fluorescent Nanoprobe for Precise Tumor Imaging.

Stimulus-responsive fluorescence imaging modality shows great promise for detection of tumor due to the advantages of high sensitivity, simplicity and noninvasiveness. However, some non-cancer regions including nodules and inflammation may also exhibit a stimulus-related characteristic, which cause the problem of nonspecific responsiveness and then cause "false positive" results for tumor recognition. Herein, hypoxia and acidic pH, two typical features strongly associated with tumor invasion, progression and metastasis in tumor microenvironment (TME), are chosen as dual stimuli to fabricate "dual lock-and-key" fluorescent nanoprobe for highly specific and precise imaging of tumor cells. Mesoporous silica coated gold nanorods (AuNR@mSiO2 ) are employed as nanocarrier and nanoquencher to load the pH-sensitive fluorescent reporter (Rho-TP). Azobenzene (azo) which can be reduced to amines by the highly expressed azoreductase under hypoxic conditions, is elected as the effective gatekeeper for AuNR@mSiO2 by forming complex with ß-cyclodextrin polymer via host-guest interaction (azo/ß-CDP). By elaborately combining the hypoxia-responsive gatekeeper and pH-responsive fluorescent signal reporter into one nanoprobe, sensitive and specific imaging of tumor cells can be realized. The fabricated dual lock-and-key fluorescent nanoprobe successfully further apply in tumor-bearing mice model, which indicate potential of early diagnosis and assessment of cancer treatment.

Triplex-Functionalized DNA Tetrahedral Nanoprobe for Imaging of Intracellular pH and Tumor-Related Messenger RNA.

A new triplex-functionalized DNA tetrahedral nanoprobe is proposed herein for monitoring pH and messenger RNA (mRNA) in living cells. Different from traditional DNA tetrahedron-based nanoprobes, DNA triplex was employed to serve as important conformational conversion elements. Inspired by the low extracellular pH in tumor cells, the mRNA-targeted H1 and H2 were stably assembled on the extended short hairpin probes of DNA tetrahedron via Hoogsteen bonding to form DNA triplex. Due to the high intracellular pH and presence of target mRNA, hybridization chain reaction (HCR) was triggered between H1 and H2 which were released from the dissociation of DNA triplex, and the generated long double-stranded DNA activated a Föster resonance energy transfer (FRET) signal indicating target mRNA expression even at very low contents. By combining the distinguishing feature of DNA triplex structure (pH-responsive) and HCR (signal amplification), sensitive imaging of intracellular pH and tumor-related mRNA can be realized. As a further application, dynamic imaging of intracellular pH and mRNA during "mitochondria-dependent" pathway apoptosis was successfully achieved in human breast cancer cells, which indicated huge potential of our proposed nanoprobe in early diagnosis and treatment of diseases.

The association between body mass index, waist circumference, waist-hip ratio and cognitive disorder in older adults.

PURPOSE: To examine the association between body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR) and cognitive disorder in older adults. METHODS: Cross-sectional data from the mini-mental state examination questionnaire and physical examination of older adults (≥65, n = 1037) were collected and analyzed. Logistic regression examined the odds ratios (ORs) of cognitive performance according to BMI, WC and WHR. RESULTS: The prevalence of cognitive dysfunction in older adults was 13.0%. The BMI-based overweight rate, obesity rate and central obesity rate calculated by either WC or WHR were 39.6, 11.4% and 66.5, 65.6%, respectively. The risk of cognitive impairment was increased in elderly individuals ≥70 years old than in those <70 years old (OR = 1.738). In addition, gender, WHR and smoking habit were also significantly different between the two age groups (P < 0.05). We examined the effects of different BMI values and WC/WHR central obesity on cognition impairment in ≥70-year-old adults and found that BMI obesity and WC/WHR central obesity had a combined effect on the incidence of cognition impairment (OR = 3.076 and OR = 3.584). CONCLUSIONS: BMI obesity and WC/WHR central obesity have a combined effect on cognitive impairment and WHR has a stronger association with cognitive impairment than WC.

Overexpression of LpCPC from Lilium pumilum confers saline-alkali stress (NaHCO3) resistance.

Lilium Pumilum with wide distribution is highly tolerant to salinity. The blue copper protein LpCPC (Lilium pumilum Cucumber Peeling Cupredoxin) gene was cloned from Lilium pumilum, which has the conserved regions of type I copper protein. Moreover, LpCPC has the closest relation to CPC from Actinidia chinensis using DNAMAN software and MEGA7 software. qRT-PCR indicated that LpCPC expression was higher in root and bulb of Lilium pumilum, and the expression of the LpCPC gene increased and reached the highest level at 12 h in bulbs under 20 mM NaHCO3. The transgenic yeast was more tolerant compared with the control under NaHCO3 stress. Compared with the wild type, overexpressing plants indicated a relatively lower degree of wilting. In addition, the chlorophyll content, soluble phenol content, and lignin content of overexpressing lines were higher than that of wild-type, whereas the relative conductivity of overexpressing plants was significantly lower than that of wild-type plants. Expression of essential genes including NHX1 and SOS1 in salt stress response pathways are steadily higher in overexpression tobacco than that in wild-types. Transgenic lines had much higher levels of CCR1 and CAD, which are involved in lignin production, compared with wild-type lines. The yeast two-hybrid technique was applied to screen probable interacting proteins interacting with LpCPC. Eight proteins interacted with LpCPC were screened, and five of which were demonstrated to be associated with plant salinity resistance. Overall, the role of gene LpCPC is mediating molecule responses in increasing saline-alkali stress resistance, indicating that it is an essential gene to enhance salt tolerance in Lilium pumilum.

Progress in Parkinson's disease animal models of genetic defects: Characteristics and application.

Parkinson's disease (PD) is the second major progressive neurodegenerative disease, which critically impacts patients' quality of life. Based on genetics, animal models of genetic defects created by gene editing technology have clear advantages in reflecting PD's pathogenesis and pathological characteristics and exploring potential therapeutic targets for PD. In this review, we summarized animal models of genetic defects in various pathogenesis of PD, including α-synuclein abnormal encoding, autophagy-lysosome system defects, ubiquitin protease system defects, and mitochondria-related dysfunction, and discuss their respective advantages, limitations, and application directions to provide a reference for the application of animal models of PD and research on anti-PD therapy.

Reductase and Light Programmatical Gated DNA Nanodevice for Spatiotemporally Controlled Imaging of Biomolecules in Subcellular Organelles under Hypoxic Conditions.

Monitoring hypoxia-related changes in subcellular organelles would provide deeper insights into hypoxia-related metabolic pathways, further helping us to recognize various diseases on subcellular level. However, there is still a lack of real-time, in situ, and controllable means for biosensing in subcellular organelles under hypoxic conditions. Herein, we report a reductase and light programmatical gated nanodevice via integrating light-responsive DNA probes into a hypoxia-responsive metal-organic framework for spatiotemporally controlled imaging of biomolecules in subcellular organelles under hypoxic conditions. A small-molecule-decorated strategy was applied to endow the nanodevice with the ability to target subcellular organelles. Dynamic changes of mitochondrial adenosine triphosphate under hypoxic conditions were chosen as a model physiological process. The assay was validated in living cells and tumor tissue slices obtained from mice models. Due to the highly integrated, easily accessible, and available for living cells and tissues, we envision that the concept and methodology can be further extended to monitor biomolecules in other subcellular organelles under hypoxic conditions with a spatiotemporal controllable approach.

Visualization of O2/ATP cross-talk in living cells with a smart fluorescent nanoprobe.

Herein, we propose a dual-responsive fluorescent nanoprobe to visualize the cross-talk between O2 and adenosine triphosphate (ATP) in living cells. We hope it will be a helpful tool for the further understanding of cellular metabolism and further facilitating risk warning in the process of adaptation to consistent environmental pressures in premalignant lesions.

Multifunctional Programmable DNA Nanotrain for Activatable Hypoxia Imaging and Mitochondrion-Targeted Enhanced Photodynamic Therapy.

Programmable DNA-based nanostructures (e.g., nanotrains, nanoflowers, and DNA dendrimers) provide new approaches for safe and effective biological imaging and tumor therapy. However, few studies have reported that DNA-based nanostructures respond to the hypoxic microenvironment for activatable imaging and organelle-targeted tumor therapy. Herein, we innovatively report an azoreductase-responsive, mitochondrion-targeted multifunctional programmable DNA nanotrain for activatable hypoxia imaging and enhanced efficacy of photodynamic therapy (PDT). Cyanine structural dye (Cy3) and black hole quencher 2 (BHQ2), which were employed as a fluorescent mitochondrion-targeted molecule and azoreductase-responsive element, respectively, covalently attached to the DNA hairpin monomers. The extended guanine (G)-rich sequence at the end of the DNA hairpin monomer served as a nanocarrier for the photosensitizer 5,10,15,20-tetrakis(4-N-methylpyridiniumyl) porphyrin (TMPyP4). Upon initiation between the DNA hairpin monomer and initiation probe, the fluorescence of Cy3 and the singlet oxygen (1O2) generation of TMPyP4 in the programmable nanotrain were effectively quenched by BHQ2 through the fluorescence resonance energy transfer (FRET) process. Once the programmable nanotrain entered cancer cells, the azo bond in BHQ2 will be reduced to amino groups by the high expression of azoreductase under hypoxia conditions; then, the fluorescence of Cy3 and the 1O2 generation of TMPyP4 will significantly be restored. Furthermore, due to the mitochondrion-targeting characteristic endowed by Cy3, the TMPyP4-loaded nanotrain would accumulate in the mitochondria of cancer cells and then demonstrate enhanced PDT efficacy under light irradiation. We expect that this programmable DNA nanotrain-based multifunctional nanoplatform could be effectively used for activatable imaging and high performance of PDT in hypoxia-related biomedical field.

Clinical Efficacy and Transcriptomic Analysis of Congrong Shujing Granules () in Patients with Parkinson's Disease and Syndrome of Shen (Kidney) Essence Deficiency.

OBJECTIVE: To evaluate the clinical efficacy and safety of Congrong Shujing Granules ( , CSGs) in treating patients with Parkinson's disease (PD) and Chinese medicine (CM) syndrome of Shen (Kidney) essence deficiency, and to investigate the potential mechanism involving efficacy through a transcriptome sequencing approach. METHODS: Eligible PD patients with syndrome of Shen essence defificiency were randomly assigned to a treatment group or a control group by a random number table, and were treated with CSGs combined with Western medicine (WM), or placebo combined with WM, respectively. Both courses of treatment lasted for 12 weeks. The Unifified Parkinson's Disease Rating Scale (UPDRS) score, the PD Question-39 (PDQ-39) score, CM Syndrome Scale score, and drug usage of all patients were evaluated before and after treatment. Safety was evaluated by clinical laboratory tests and electrocardiographs. Blood samples from 6 patients in each group were collected before and after the trial and used for transcriptomic analysis by gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Differentially expressed genes were validated using reverse transcription-polymerase chain reaction. RESULTS: A total of 86 PD patients were selected from the Third Affifiliated People's Hospital of Fujian University of Traditional Chinese Medicine between January 2017 and December 2017. Finally, 72 patients completed the trial, including 35 in the treatment group and 37 in the control group. When compared with the control group after treatment, patients in the treatment group showed signifificant decreases in UPDRS sub-II score, PDQ-39 score, CM syndrome score, and Levodopa equivalent dose (P<0.05). During the treatment course, no signifificant changes were observed in safety indicators between the two groups (P>0.05). A possible mechanism of clinical effificacy was proposed that involved regulating cell metabolism-related processes and ribosome-related pathways. Treatment with CSGs had shown to affect relevant gene loci for PD, including AIDA, ANKRD36BP2, BCL2A1, BCL2L11, FTH1P2, GCH1, HPRT1, NFE2L2, RMRP, RPS7, TGFBR1, WIPF2, and COX7B. CONCLUSIONS: CSGs combined with WM can be used to treat PD patients with CM syndrome of Shen essence defificiency with a good safety. The possible mechanism of action and relevant gene loci were proposed. (Registration No. ChiCTR-IOR-16008394).

The Effect of Traditional Chinese Medicine on Neural Stem Cell Proliferation and Differentiation.

Neural stem cells (NSCs) are special types of cells with the potential for self-renewal and multi-directional differentiation. NSCs are regulated by multiple pathways and pathway related transcription factors during the process of proliferation and differentiation. Numerous studies have shown that the compound medicinal preparations, single herbs, and herb extracts in traditional Chinese medicine (TCM) have specific roles in regulating the proliferation and differentiation of NSCs. In this study, we investigate the markers of NSCs in various stages of differentiation, the related pathways regulating the proliferation and differentiation, and the corresponding transcription factors in the pathways. We also review the influence of TCM on NSC proliferation and differentiation, to facilitate the development of TCM in neural regeneration and neurodegenerative diseases.

Cistanche tubulosa Protects Dopaminergic Neurons through Regulation of Apoptosis and Glial Cell-Derived Neurotrophic Factor: in vivo and in vitro.

Parkinson's disease (PD) is a neurodegenerative disease with the pathological hallmark of reduced nigrostriatal dopamine. In traditional Chinese medicine (TCM) clinical practice, the nanopowder of Cistanche tubulosa has therapeutic effects on PD. To identify the therapeutic mechanism, this study tested the protective effect of different doses of MPP+-induced toxicity in MES23.5 cells using the MTT assay and in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice (vehicles). Immunohistochemistry was used to assess cytomorphology and tyrosine hydroxylase (TH) expression. Behavioral tests in vehicles, high performance liquid chromatography (HPLC) tests in dopamine, immunohistochemistry and western blot analysis were used to detect the expression of TH, glial cell line-derived neurotrophic factor (GDNF) and its receptors. Our results demonstrated that the C. tubulosa nanopowder improved the viability of MPP+-treated cells, increased TH expression and reduced the number of apoptotic cells. It also increased Bcl2 protein expression and suppressed Bax protein expression in MPP+-treated cells in a dose-dependent manner. In addition, C. tubulosa nanopowder improved the behavioral deficits in vehicle mice, reduced the stationary duration of swimming, enhanced the ability for spontaneous activity and increased the expression of GDNF, the GDNF family receptor alpha (GFRα1) and Ret in cells of the substantia nigra (SN). Furthermore, the protein expression of GDNF, GFRα1 and Ret increased after treatment with different doses of C. tubulosa nanopowder, with a significant difference between the high-dose and vehicle groups. The protein expression of Bcl2 and Bax were similar in the in vivo and in vitro, which suggested that C. tubulosa nanopowder has anti-apoptotic effects in neurons.