Corydecusines A-H, new phthalideisoquinoline hemicetal alkaloids from the bulbs of Corydalis decumbens inhibit Tau pathology by activating autophagy mediated by AMPK-ULK1 pathway.

Twelve phthalideisoquinoline hemiacetal alkaloids including eight new ones (1-8) and one natural alkaloid characterized by an aziridine moiety with unassigned NMR data (9), were isolated and identified from the bulbs of Corydalis decumbens. Their structures were established by comprehensive analyses of HRESIMS, NMR, X-ray crystallography, and ECD analyses. The unambiguously established structures of the phthalideisoquinoline hemiacetal alkaloids indicated that the absolute configurations of C-1, C-9, and C-7' were confusable only relied on coupling constants. A summary of their ECD spectra was concluded and provided an insight for C-1, C-9, and C-7' absolute configuration assignment. These new compounds were evaluated to induce autophagy flux through flow cytometry analysis. Moreover, compounds 2 and 6 could significantly induce autophagy and inhibit Tau pathology by AMPK-ULK1 pathway activation, which provided an avenue for anti-AD lead compounds discovery.

Two new jatrophane diterpenoids from Euphorbia helioscopia with activity towards autophagic flux.

Nine jatrophane diterpenoids were isolated from the whole plant Euphorbia helioscopia, including two new ones, helioscopnins A (1) and B (2). Comprehensive spectroscopic data analysis and ECD calculations elucidated their structures, including absolute configurations. All compounds were evaluated for bioactivity towards autophagic flux by flow cytometry using HM mCherry-GFP-LC3 cells. Compounds 1, 3, 4, 5, 8, and 9 significantly increased autophagic flux.

Entanglement generation and steering implementation in a double-cavity-magnon hybrid system.

We demonstrate a scheme for the generation of bipartite and tripartite entanglement, as well as he implementation of stable and controllable long-distance one-way and asymmetric two-way steering in a cavity-magnon hybrid system. This system consists of a magnon mode and two coupled microwave cavities. The first cavity is driven by a flux-driven Josephson parametric amplifier, which generates squeezed vacuum fields, and is coupled to the other cavity through optical tunneling interaction. The second cavity and magnon mode are coupled through magnetic dipole interaction. We find that under weak coupling between the two cavities, and strong coupling between the second cavity and magnon mode, remote controllable one-way steering and tripartite entanglement can be achieved. Our scheme may have potential applications in quantum information.

Entanglement enhancement and EPR steering based on a PT-symmetric-like cavity-opto-magnomechanical hybrid system.

We investigate the enhancement of entanglement and EPR steering in a parity-time(PT-) symmetric-like cavity-opto-magnomechanical system. The system consists of an optical cavity, a magnon mode in a ferromagnetic crystal, a phonon mode, and a microwave cavity. Our findings demonstrate that microwave-cavity gain significantly boosts distant quantum entanglement and greatly improves the robustness of bipartite entanglement against environment temperature. Additionally, we observe an enhancement of tripartite entanglement within the system and uncover the phenomenon of entanglement transfer. Notably, we also achieve one-way steering and two-way asymmetric steering in the system. This study offers insights into the integration of traditional optomechanics and cavity magnomechanics, presenting a novel approach to manipulate asymmetric quantum steering between two distant macroscopic objects. The implications of our research extend to the fields of quantum state preparation and quantum information.

Perforalactones D and E, two new C-20 quassinoids with potential activity to induce lysosomal biogenesis from the twigs of Harrisonia perforata (Blanco) Merr.

Two new quassinoids (1 and 2) were isolated from the twigs of Harrisonia perforata (Blanco) Merr. Perforalactone E (2) possesses an uncommon hexacyclic 1α,12α:5α,13α-dicyclo-9ßH-picrasane skeleton. Its structure was determined based on spectroscopic data and X-ray crystallography. Compounds 1 and 2 could significantly induce lysosomal biogenesis through transcriptional activation of lysosomal genes.

Entanglement enhanced by Kerr nonlinearity in a cavity-optomagnonics system.

We present a method to enhance steady-state bipartite and tripartite entanglement in a cavity-optomagnonics system by utilizing the Kerr nonlinearity originating from the magnetocrystalline anisotropy. The system comprises two microwave cavities and a magnon and represents the collective motion of several spins in a macroscopic ferrimagnet. We prove that Kerr nonlinearity is reliable for the enhancement of entanglement and produces a small frequency shift in the optimal detuning. Our system is more robust against the environment-induced decoherence than traditional optomechanical systems. Finally, we briefly analyze the validity of the system and demonstrate its feasibility for detecting the generated entanglement.

Expression characteristics of long noncoding RNA uc.322 and its effects on pancreatic islet function.

Increasing evidence indicates that long noncoding RNAs (lncRNAs) perform special biological functions by regulating gene expression through multiple pathways and molecular mechanisms. The aim of this study was to explore the expression characteristics of lncRNA uc.322 in pancreatic islet cells and its effects on the secretion function of islet cells. Bioinformatics analysis was used to detect the lncRNA uc.322 sequence, location, and structural features. Expression of lncRNA uc.322 in different tissues was detected by quantitative polymerase chain reaction analyses. Quantitative polymerase chain reaction, Western blot analysis, adenosine triphosphate determination, glucose-stimulated insulin secretion, and enzyme-linked immunosorbent assay were used to evaluate the effects of lncRNA uc.322 on insulin secretion. The results showed that the full-length of lncRNA uc.322 is 224 bp and that it is highly conserved in various species. Bioinformatics analysis revealed that lncRNA uc.322 is located on chr7:122893196-122893419 (GRCH37/hg19) within the SRY-related HMG-box 6 gene exon region. Compared with other tissues, lncRNA uc.322 is highly expressed in pancreatic tissue. Upregulation of lncRNA uc.322 expression increases the insulin transcription factors pancreatic and duodenal homeobox 1 and Forkhead box O1 expression, promotes insulin secretion in the extracellular fluid of Min6 cells, and increases the adenosine triphosphate concentration. On the other hand, knockdown of lncRNA uc.322 has opposite effects on Min6 cells. Overall, this study showed that upregulation of lncRNA uc.322 in islet ß-cells can increase the expression of insulin transcription factors and promote insulin secretion, and it may be a new therapeutic target for diabetes.

GLP-1RA promotes brown adipogenesis of C3H10T1/2 mesenchymal stem cells via the PI3K-AKT-mTOR signaling pathway.

OBJECTIVE: In this study, we investigated whether the GLP-1RA, liraglutide, affected differentiation of C3H10T1/2 mesenchymal stem cells (MSCs) to mature brown adipocytes and involvement of PI3K/AKT/mTOR signaling pathway in this process. METHODS: C3H10T1/2 MSCs were induced to differentiate into brown adipocytes and treated with liraglutide (10 nM and 100 nM) for 0, 2, 4, 6 and 8 days with or without PI3K inhibitor LY294002. Oil red O staining was used for lipid droplet staining and cell proliferation was determined by cell counts. Quantitative realtime PCR was employed to determine the expression of adipogenic and mitochondrial genes, mitochondrial DNA (mtDNA). Western blot analyses were used for quantification of protein levels in PI3K/AKT/mTOR signaling pathway. RESULTS: Liraglutide increased proliferation of C3H10T1/2 MSCs and formation of multilocular lipid droplets during differentiation. Adipogenic and mitochondrial genes, mtDNA were promoted by liraglutide. Moreover, liraglutide treatment increased the levels of phosphorylated AKT and mTOR. LY294002 not only attenuated differentiation of C3H10T1/2 MSCs into brown adipocytes, but also reduced phosphorylated AKT and mTOR levels. However, co-treatment with liraglutide and LY294002 decreased the expression of adipogenic and mitochondrial genes, mtDNA, and phosphorylated AKT and mTOR levels compared to C3H10T1/2 MSCs treated with liraglutide 100 nM. CONCLUSION: GLP-1RA promotes brown adipogenesis of C3H10T1/2 mesenchymal stem cells, and PI3K/AKT/mTOR signaling pathway is involved in GLP-1RA-mediated promotion of differentiation.

Distinct DNA methylomes of human placentas between pre-eclampsia and gestational diabetes mellitus.

BACKGROUND: The placenta acts not only as a conduit of nutrient and waste exchange between mother and developing fetus but also functions as a regulator of the intrauterine environment. Pre-eclampsia (PE) and gestational diabetes mellitus (GDM) are leading causes of complications during pregnancy. Pathophysiologies show that they are associated with one another. Epigenetics provides a link between environmental factors that have previously been linked to poor pregnancy outcomes and fetal programming. METHODS AND RESULTS: The present study investigated genome-wide DNA methylation changes in PE and GDM compared with control subjects through DNA methylation microarray. We found that the methylation patterns of placentas from PE and GDM women were similar; 64.4% of the annotated genes with differential methylation presented concordant changes between PE and GDM patients. Significantly, the same functional processes were affected by PE and GDM, with cell adhesion and cell differentiation being the most populated clusters and including genes related to carbohydrate metabolism and lipid metabolism. CONCLUSION: Our work showed that of DNA methylation patterns in human placentas are reliably and significantly associated with PE and GDM. DNA methylation status in the human placenta can function as a marker for the intrauterine environment and potentially play a functional role in PE and GDM development.

Monoterpenoid indole alkaloid dimers from Kopsia arborea inhibit cyclin-dependent kinase 5 and tau phosphorylation.

Three undescribed monoterpenoid indole alkaloid dimers (kopoffines A-C, which are connected via a methylene unit) and with nine known alkaloids were isolated and identified from the fruits of Kopsia arborea Blume. Their structures, including their absolute configurations, were established by HRESIMS, NMR, single-crystal X-ray diffraction, and ECD analyses. Kopoffines A-C showed significant inhibition against cyclin-dependent kinase 5 (IC50: 0.34-2.18 µM). Western blotting analyses showed that kopoffines A-C significantly decreased the protein levels of CDK5 and phospho-CDK5 (Tyr15) (pCDK5) at concentrations of 2.5 and 10 µM. The levels of phospho-Tau (Thr217) (pTau217, a new biomarker of AD), and phospho-Tau (Ser396) (pTau396), which play major roles in the formation of neurofibrillary tangles , were decreased by the kopoffines A-C treatment. Molecular docking studies indicated that kopoffines A-C could form stable interactions with CDK5.

[Synthesis and characterization of new lanthanide complexes using pipemidic acid (PPA) and dioxane as ligands].

Eu(PPA)3 dioxane and Tb(PPA)3 dioxane were synthesized by firstly adopting dioxane as second ligand and using pipemidic acid (PPA) as first ligand. In contrast with two kinds of binary lanthanide complexes Eu(PPA)3 and Tb(PPA)3, the photoluminescent intensities of Eu (PPA)3 dioxane and Tb (PPA)3 dioxane are much stronger, especially for that of Tb(PPA)3 dioxane. The enhancement of photoluminescent intensities of Eu(PPA)3 dioxane and Tb(PPA)3 dioxane is because of the replacement of dioxane for water bonded to Eu3+ and Tb3+, by which the energy loss through heat oscillation will be inhibited. The as-synthesized lanthanide complexes were characterized by FT-IR, photoluminescence spectra and photoluminescence lifetime. The lifetime of Eu(PPA)3 dioxane and Tb(PPA) dioxane remarkably changed compared with those of Eu(PPA)3 and Tb(PPA)3. However, there is much difference for the lifetime change of as-synthesized lanthanide complexes formed by Eu3+ and Tb3+, which shows that there is different energy transfer process for the lanthanide complexes formed by Eu3+ and Tb3+. The synthesis of lanthanide complexes using dioxane as second ligand will provide a new method to detect the existence of dioxane.

Harpertrioate A, an A,B,D-seco-Limonoid with Promising Biological Activity against Alzheimer's Disease from Twigs of Harrisonia perforata (Blanco) Merr.

Harpertrioate A (1), an A,B,D-seco-limonoid with a rearranged ring B incorporating exocyclic C-30, was isolated from the EtOAc extract of Harrisonia perforata twigs. Its structure, including absolute configurations, was determined on the basis of spectroscopic data and X-ray crystallography. This compound exhibited biological activities against Alzheimer's disease by reducing Aß42 and Aß40 production and shifting APP processing toward nonamyloidogenic pathway. The effect of 1 on the Aß production was comparable to that of gemfibrozil.

The anatomy of the skin of the Chinese tree shrew is very similar to that of human skin.

The Chinese tree shrew (Tupaia belangeri chinensis) is a small mammal closely related to primates. It has a small body size, low maintenance cost, and a relatively short reproductive cycle, all of which has made it the ideal model for the study of a variety of human diseases. In this study, we compared the anatomy of the skin of the Chinese tree shrew with that of the rhesus macaque, mouse and human, with the intention of providing the basic data required for the creation of skin disease models using this animal. Paraffin sections, hematoxylin-eosin (H&E) staining, masson staining and immunohistochemical techniques were used to examine the dorsal skin structure of the Chinese tree shrew. The epidermis was shown to be composed of 1-2 layers of cells. There were hair follicles, sebaceous glands and sweat glands in the dermis and the subcutaneous tissue, with apocrine glands being more common than eccrine glands. Both Keratin5 (KRT5) and Keratin10 (KRT10) were expressed in the skin of the Chinese tree shrew, with a localization in the cytoplasm. Overall, the skin morphology and histology of the Chinese tree shrew was basically the same as that of the human. We propose that the Chinese tree shrew has a strong potential to be used for creating animal models to help elucidate the molecular mechanisms underlying a variety of skin diseases.

Emergence of Zika virus infection in China.

Currently, Zika virus (ZIKV) is spreading across the world and no ZIKV infection cases have ever been reported in China. Here, we aimed to determine whether ZIKV infection exists in China. Blood samples of 273 healthy individuals were collected from Nanning City, Guangxi Province, China in March 2019. We found that 9.5% (26/273) and 1.8% (5/273) of healthy persons were positive to ZIKV total antibody (IgG and/or IgM) IgM antibody, respectively. All ZIKV positive plasma samples were negative to Dengue virus and West Nile virus. Among the ZIKV antibody positive plasma samples, 65.4% (17/26) exhibited neutralizing activity to ZIKV. Followed up studies showed that none had clinical symptoms of ZIKV infection and oversea experience. Together, our study indicates that endemic ZIKV infections emerge in China, which not only suggested that ZIKV posed a potential threat to public health in China, but also expand the ZIKV epidemic areas in East and Southeast Asia.

[Prognostic significance of metastatic lymph node ratio in colorectal cancer].

OBJECTIVE: To investigate the prognostic significance of metastatic lymph node ratio in patients with colorectal cancer. METHODS: The clinicopathological data of 303 surgically treated patients with colorectal cancer were retrospectively analyzed. Spearman correlation analysis was used to determine the correlation coefficient. The survival was analyzed using Kaplan-Meier method, and the survival difference was assessed by Log-rank test. Multivariate analysis was performed using Cox proportional hazard regression model in forward stepwise regression. Receiver working characteristic curve was used to compare the accuracy of the metastatic lymph nodes ratio in predicting the death of patients at 5 years postoperatively with that of the number of metastatic lymph nodes. RESULTS: The MLR was not correlated with the total number of dissected lymph nodes (Spearman correlation coefficient: -0.099, P > 0.05), but the positive rate of metastatic lymph nodes did (correlation coefficient: 0.107, P < 0.05). Kaplan-Meier survival analysis revealed that the MLR significantly influenced the postoperative survival time (Log-rank chi(2) = 42.878, P < 0.01), even in the patients with less than 12 resected lymph nodes. The 5-year survival rates for rN0, rN1, rN2 and rN3 were 90.9%, 68.9%, 54.7% and 39.4%, respectively. There was a significant difference between the different stages (P < 0.01). Cox proportional hazard regression model analysis showed that the metastatic lymph node ratio was an independent prognostic factor. (EXP(B) = 7.809, P < 0.01). There was no significant difference between metastatic lymph node ratio and the number of metastatic lymph nodes in predicting the death of patients at 5 years postoperatively based on the area under the receiver working characteristic curve. CONCLUSION: The metastatic lymph node ratio in colorectal cancer patients is not correlated with the total number of dissected lymph nodes. The metastatic lymph node ratio is a major independent prognostic factor for patients with colorectal cancer. The ability of metastatic lymph node ratio in predicting the death of colorectal cancer patients at 5 years postoperatively is the same as that of the number of metastatic lymph nodes.

Wide Angle of Incidence-Insensitive Polarization-Independent THz Metamaterial Absorber for Both TE and TM Mode Based on Plasmon Hybridizations.

An ultra-wide-angle THz metamaterial absorber (MA) utilizing sixteen-circular-sector (SCR) resonator for both transverse electric (TE) and transverse magnetic (TM) mode is designed and investigated numerically. At normal incidence, the absorptivity of the proposed MA is higher than 93.7% at 9.05 THz for different polarization angles, due to the rotational symmetry structure of the unit cell. Under oblique incidence, the absorptivity can still exceed 90%, even when the incident angle is up to 70° for both TE and TM mode. Especially, the frequency variation in TE mode is less than 0.25% for different incident angles from 0° to 70°. The electric field (Ez) distributions are used to explain the absorption mechanism. Numerical simulation results show that the high absorption with wide-angle independence stems from fundamental dipole resonance and gap surface plasmons. The broadband deep-infrared MA is also obtained by stacking three metal-dielectric layers. The designed MA has great potential in bolometric pixel elements, biomedical sensors, THz imaging, and solar cells.

Adiabatic Generation of N-quNit Singlet States with Cavity QED.

We present a theoretical scheme to generate N-quNit singlet states with N 3 via adiabatic passage. In this protocol, the system may be robust against both experimental parameter fluctuations and dissipations along dark states. In addition, during the whole procedure, quantum information is almost fully transferred between atomic ground states. It reduces the influence of dissipations such as atomic spontaneous emissions and cavity decays. Thus, the presented proposal may be feasible based on current technologies.

Effects of Ganlu Xiaodu Pills and Its Residues on PSGL-1 and Proinflammatory Cytokines in CoxA16 Mouse Model / 中国中医药信息杂志

Objective To investigate the effects of Ganlu Xiaodu Pills and its residues on PSGL-1 and proinflammatory cytokines in Coxsackie virus A16 (CoxA16) mouse model; To discuss its antiviral mechanism of action. Methods Totally 150 ICR mice at age of 7 days were randomly divided into normal group, model group, all-side group, aromatic residual group, clearing residual group and removing residual group, with 25 mice in each group. Except for normal group, other groups were injected intraperitoneally with 20 μL of 107TCID50 CoxA16 standard stock solution to establish models. Except for normal group and model group, other groups were given relevant medicine for intervention. The expressions of PSGL-1, TNF-α, IL-1β and IL-4 and histopathological observation were detected after 10 days of medication. Results Except for the normal group, the existence of a large number of CoxA16 in other groups of mouse muscle tissues proved successful modeling. HE staining showed that Ganlu Xiaodu Pills and residual could reduce damage to the muscle by CoxA16 virus. Compared with the normal group, the expression of PSGL-1 protein in the model group increased (P<0.01); compared with the model group, all-side group, aromatic residue group, clearing residual group, removing residual group inhibited the expression of PSGL-1 protein, reduced the inflammatory factors of TNF-α, IL-1β, and IL-4 (P<0.01). Conclusion Ganlu Xiaodu Pills and its residues have anti-inflammatory effects, and the all-side group shows the best efficacy.

[Annual change of phytoplankton ecological features in Fangchenggang Bay of Guangxi, South China].

In March, June, September, and December 2007, investigations were conducted on the species composition, dominant species, community structure, and abundance distribution of phytoplankton in the Fangchenggang Bay of Guangxi. Based on the investigation data, the phytoplankton abundance, biotic index, and their correlations with environmental factors were analyzed. A total of 138 species of 54 genera were identified, among which, 112 species belonged to 37 genera of diatoms, 21 species belonged to 12 genera of dinoflagellates, 2 species belonged to chrysophyta, 2 species belonged to chlorophyta, and 1 species belonged to cyanophyta. In whole year, the dominant species was Skeletonema costatum. The species number had a trend decreasing from the outer to the inner of the Bay and from spring to winter, while the cell abundance was decreased from the inner to the outer of the Bay. There was an obvious annual change in the cell abundance, being the highest (151.39 x 10(4) cells x dm(-3)) in summer (June) and the lowest (0.35 x 10(4) cells x dm(-3)) in winter (December). In spring, both the diversity and the species number were higher. Correlation analysis demonstrated that the distribution of phytoplankton community had definite correlations with water nutrient content, temperature and salinity. At the observation stations 1 and 2 in west Bay, due to the effects of Fangcheng River runoff and hydrodynamic forces such as tide, water salinity was lower and nutrient content was higher, and accordingly, S. costatum cells in summer could greatly reproduce, even result in high probability of red tide.