Moiré enhanced charge density wave state in twisted 1T-TiTe2/1T-TiSe2 heterostructures.

Nanoscale periodic moiré patterns, for example those formed at the interface of a twisted bilayer of two-dimensional materials, provide opportunities for engineering the electronic properties of van der Waals heterostructures1-11. In this work, we synthesized the epitaxial heterostructure of 1T-TiTe2/1T-TiSe2 with various twist angles using molecular beam epitaxy and investigated the moiré pattern induced/enhanced charge density wave (CDW) states with scanning tunnelling microscopy. When the twist angle is near zero degrees, 2 × 2 CDW domains are formed in 1T-TiTe2, separated by 1 × 1 normal state domains, and trapped in the moiré pattern. The formation of the moiré-trapped CDW state is ascribed to the local strain variation due to atomic reconstruction. Furthermore, this CDW state persists at room temperature, suggesting its potential for future CDW-based applications. Such moiré-trapped CDW patterns were not observed at larger twist angles. Our study paves the way for constructing metallic twist van der Waals bilayers and tuning many-body effects via moiré engineering.

Observation of Electronic Strong Correlation in VTe_{2}-2sqrt[3]×2sqrt[3] Monolayer.

Strong electron correlation under two-dimensional limit is intensely studied in the transition metal dichalcogenides monolayers, mostly within their charge density wave (CDW) states that host a star of David period. Here, by using scanning tunneling microscopy and spectroscopy and density functional theory calculations with on-site Hubbard corrections, we study the VTe_{2} monolayer with a different 2sqrt[3]×2sqrt[3] CDW period. We find that the dimerization of neighboring Te-Te and V-V atoms occurs during the CDW transition, and that the strong correlation effect opens a Mott-like full gap at Fermi energy (E_{F}). We further demonstrate that such a Mott phenomenon is ascribed to the combination of the CDW transition and on-site Coulomb interactions. Our work provides a new platform for exploring Mott physics in 2D materials.

Diterpenoids from Euphorbia helioscopia and their enhancement of NK cell-mediated killing of NSCLC cells.

Fourteen previously undescribed diterpenoids, including an unusual diterpenoid (1) with a 9,10-seco-jatrophane skeleton, ten jatrophane-type diterpenoids (2-11), two lathyrane-type diterpenoids (12, 13), and an abietane-type diterpenoid (14), together with thirty-six known ones (15-50), were isolated from the whole plants of Euphorbia helioscopia L. The structures of the new isolates were characterized by spectroscopic methods, single-crystal X-ray diffraction analysis, and computational prediction of ECD and chemical shifts. Thirty-nine abundant diterpenoids were evaluated for their enhancement of NK cell-mediated killing of NSCLC cells. As a result, compounds 24, 33, and 41 were found to significantly enhance the killing activity of NK cells towards H1299-luci cells and A549-luci cells at the concentration of 2.5 µM.

Protective Effects of 28-O-Caffeoyl Betulin (B-CA) on the Cerebral Cortex of Ischemic Rats Revealed by a NMR-Based Metabolomics Analysis.

28-O-caffeoyl betulin (B-CA) has been demonstrated to reduce the cerebral infarct volume caused by transient middle cerebral artery occlusion (MCAO) injury. B-CA is a novel derivative of naturally occurring caffeoyl triterpene with little information associated with its pharmacological target(s). To date no data is available regarding the effect of B-CA on brain metabolism. In the present study, a 1H-NMR-based metabolomics approach was applied to investigate the therapeutic effects of B-CA on brain metabolism following MCAO in rats. Global metabolic profiles of the cortex in acute period (9 h after focal ischemia onset) after MCAO were compared between the groups (sham; MCAO + vehicle; MCAO + B-CA). MCAO induced several changes in the ipsilateral cortex of ischemic rats, which consequently led to the neuronal damage featured with the downregulation of NAA, including energy metabolism dysfunctions, oxidative stress, and neurotransmitter metabolism. Treatment with B-CA showed statistically significant rescue effects on the ischemic cortex of MCAO rats. Specifically, treatment with B-CA ameliorated the energy metabolism dysfunctions (back-regulating the levels of succinate, lactate, BCAAs, and carnitine), oxidative stress (upregulating the level of glutathione), and neurotransmitter metabolism disturbances (back-regulating the levels of γ-aminobutyric acid and acetylcholine) associated with the progression of ischemic stroke. With the administration of B-CA, the levels of three phospholipid related metabolites (O-phosphocholine, O-phosphoethanolamine, sn-glycero-3-phosphocholine) and NAA improved significantly. Overall, our findings suggest that treatment with B-CA may provide neuroprotection by augmenting the metabolic changes observed in the cortex following MCAO in rats.

Minor immunosuppressive spiroorthoester group-containing pregnane glycosides from the root barks of Periploca sepium.

LC-MS guided chemical investigation of the periploside-rich extract of the root barks of Periploca sepium afforded six new minor pregnane glycosides, named periplosides A1-A6 (1-6). Their structures were characterized on the basis of extensive spectroscopic analysis. Compounds 1-6 were evaluated for their inhibitory activities against the proliferation of T and B lymphocytes in vitro, among them, compound 5 exhibited significant inhibitory activities and the most favorite selective index (SI) values against the proliferation of T lymphocyte (IC50 = 0.30 µM, SI = 176) and B lymphocyte (IC50 = 0.55 µM, SI = 97).

Erratum: Realization of a Metallic State in 1T-TaS_{2} with Persisting Long-Range Order of a Charge Density Wave [Phys. Rev. Lett. 123, 206405 (2019)].

This corrects the article DOI: 10.1103/PhysRevLett.123.206405.

Realization of a Metallic State in 1T-TaS_{2} with Persisting Long-Range Order of a Charge Density Wave.

Metallization of 1T-TaS_{2} is generally initiated at the domain boundary of a charge density wave (CDW), at the expense of its long-range order. However, we demonstrate in this study that the metallization of 1T-TaS_{2} can be also realized without breaking the long-range CDW order upon surface alkali doping. By using scanning tunneling microscopy, we find the long-range CDW order is always persisting, and the metallization is instead associated with additional in-gap excitations. Interestingly, the in-gap excitation is near the top of the lower Hubbard band, in contrast to a conventional electron-doped Mott insulator where it is beneath the upper Hubbard band. In combination with the numerical calculations, we suggest that the appearance of the in-gap excitations near the lower Hubbard band is mainly due to the effectively reduced on-site Coulomb energy by the adsorbed alkali ions.

[Physiology and genetics research progress of teat traits in pigs].

The pig teat traits are important indices of genetic improvement in pig breeding, which belong to reproductive traits and can directly affect the sows lactation rate and piglet survival rate. Understanding the genetic mechanism underlying the variation of teat traits is of immense value for the improvement of pig reproductive performance. However, the genetic mechanism underlying teat traits (including teat number, type, location distribution, and fluctuating asymmetry) remains elusive. In this review, we summarize the studies on physiology and genetics of teat traits in pigs, including the development process of the mammary gland, the QTL mapping, and candidate gene researches. This review aims to provide a new perspective for the identification of causal mutations and major genes affecting the teat traits and revealing the complex genetic mechanism of the differences in teat number, type and location distribution during embryonic development in pigs.

Spiroorthoester group-containing pregnane glycosides from the root barks of Periploca chrysantha and their inhibitory activities against the proliferation of B and T lymphocytes.

Phytochemical investigation of the root barks of Periploca chrysantha D. S. Yao, X. C. Chen et J. W. Ren (Asclepiadaceae) led to the elucidation of four new spiroorthoester group-containing pregnane glycosides (1-4), named periplosides W-Y and 3-O-formyl-periploside F. Their structures were elucidated on the basis of extensive spectroscopic analysis. The four new pregnane glycosides (1-4) were found to exhibit significantly inhibitory activities against the proliferation of B and T lymphocytes and favorable selective index comparable to those of cyclosporin A.

Absolute Configuration of Periplosides C and F and Isolation of Minor Spiro-orthoester Group-Containing Pregnane-type Steroidal Glycosides from Periploca sepium and Their T-Lymphocyte Proliferation Inhibitory Activities.

Further phytochemical investigation of the root bark of Periploca sepium afforded nine new spiro-orthoester group-containing pregnane-type glycosides termed periplosides O-V and 3-O-formyl-periploside A. The structures of these glycosides along with the absolute configuration of the unique seven-membered formyl acetal-bridged spiro-orthoester function and the 4,6-dideoxy-3-O-methyl-Δ3-2-hexosulosyl moiety were elucidated on the basis of spectroscopic data interpretation and chemical transformation. The absolute configurations of the major compounds periplosides C and F were established by single-crystal X-ray diffraction analysis. The isolated compounds were evaluated for their inhibitory activities against the proliferation of T-lymphocytes. As a result, periploside C, the most abundant glycoside containing a spiro-orthoester moiety found in the plant, exhibited the most favorite selective index value (SI = 82.5). The length and constitution of the saccharide chain in the periplosides were found to influence the inhibitory activity and the SI value.

Dual anti-ischemic effects of rosmarinic acid n-butyl ester via alleviation of DAPK-p53-mediated neuronal damage and microglial inflammation.

The discovery of efficacious anti-ischemic drugs remains a challenge. Recently we have found that rosmarinic acid n-butyl ester (RABE), a derivative of rosmarinic acid, significantly protects SH-SY5Y cells against oxygen glucose deprivation (OGD)-induced cell death. In the present study we simultaneously investigated the effects of RABE on the two key players in the pathophysiology of cerebral ischemia, ischemic neuronal damage and microglial inflammation. Pretreatment with RABE (1, 10 µmol/L) dose-dependently attenuated OGD- or H2O2-induced reduction of the viability of SH-SY5Y neuroblastoma cells. RABE pretreatment concurrently reduced the apoptotic cell rate, down-regulated the expression of the pro-apoptotic proteins Bax and p53, and up-regulated the expression of the anti-apoptotic protein phosphorylated death-associated protein kinase (DAPK). Furthermore, pretreatment with RABE (3 µmol/L) markedly inhibited lipopolysaccharide (LPS)-induced increases in the release of TNF-α, IL-1ß, NO and PGE2, and the expression levels of iNOS, and COX-2 in cultured rat microglial cells. In conclusion, these results reveal for the first time the potential anti-ischemic effects of RABE on neuronal and glial cells and elucidate the molecular mechanisms involved in its dual beneficial profiles in vitro. RABE may be a promising drug lead/candidate for the treatment of ischemic stroke.

Aromatic monoterpenoid glycosides from the seeds of Paeonia ostii.

Phytochemical investigation into the seeds of Paeonia ostii T. Hong et J. X. Zhang (Paeoniaceae) led to the identification of three new aromatic monoterpenoid glycosides, named paeostisides A-C (1-3), along with one known compound. Their structures were identified by spectroscopic analysis and chemical method.

Identification and Evaluation of Antiepileptic Activity of C21 Steroidal Glycosides from the Roots of Cynanchum wilfordii.

Nine new C21 steroidal glycosides, named cynawilfosides A-I (1-9), along with 12 known compounds were isolated from the roots of Cynanchum wilfordii. The structures of the new compounds were elucidated by spectroscopic analysis and chemical methods. The five major components, cynawilfoside A (1), cynauricoside A (11), wilfoside C1N (16), wilfoside K1N (17), and cyanoauriculoside G (18), exhibited significant protection activity in a maximal electroshock (MES)-induced mouse seizure model with ED50 values of 48.5, 95.3, 124.1, 72.3, and 88.1 mg/kg, respectively.

Caffeoyl Triterpenoid Esters as Potential Anti-ischemic Stroke Agents from Celastrus orbiculatus.

Three new triterpenoids, celastrusins A-C (1-3), together with 3-O-caffeoyl-α-amyrin (4) were isolated from the root bark of Celastrus orbiculatus. Their structures were identified by spectroscopic analysis, X-ray crystallography using Cu Kα radiation, and the comparison of both observed and reported spectroscopic data. An in vitro bioassay revealed that the caffeoyl triterpenoid esters 1, 3, and 4 possess neuroprotective effects against oxygen-glucose deprivation (OGD) induced SH-SY5Y cell damage. Further animal studies indicated that compound 1 significantly reduced brain infarction after transient middle cerebral artery occlusion (MCAO) in rats using a 10 mg/kg (i.v.) dose.

Chlorogenic acid analogues from Gynura nepalensis protect H9c2 cardiomyoblasts against H2O2-induced apoptosis.

AIM: Chlorogenic acid has shown protective effect on cardiomyocytes against oxidative stress-induced damage. Herein, we evaluated nine caffeoylquinic acid analogues (1-9) isolated from the leaves of Gynura nepalensis for their protective effect against H2O2-induced H9c2 cardiomyoblast damage and explored the underlying mechanisms. METHODS: H9c2 cardiomyoblasts were exposed to H2O2 (0.3 mmol/L) for 3 h, and cell viability was detected with MTT assay. Hoechst 33342 staining was performed to evaluate cell apoptosis. MMPs (mitochondrial membrane potentials) were measured using a JC-1 assay kit, and ROS (reactive oxygen species) generation was measured using CM-H2 DCFDA. The expression levels of relevant proteins were detected using Western blot analysis. RESULTS: Exposure to H2O2 markedly decreased the viability of H9c2 cells and catalase activity, and increased LDH release and intracellular ROS production; accompanied by a loss of MMP and increased apoptotic rate. Among the 9 chlorogenic acid analogues as well as the positive control drug epigallocatechin gallate (EGCG) tested, compound 6 (3,5-dicaffeoylquinic acid ethyl ester) was the most effective in protecting H9c2 cells from H2O2-induced cell death. Pretreatment with compound 6 (1.56-100 µmol/L) dose-dependently alleviated all the H2O2-induced detrimental effects. Moreover, exposure to H2O2 significantly increased the levels of Bax, p53, cleaved caspase-8, and cleaved caspase-9, and decreased the level of Bcl-2, resulting in cell apoptosis. Exposure to H2O2 also significantly increased the phosphorylation of p38, JNK and ERK in the H9c2 cells. Pretreatment with compound 6 (12.5 and 25 µmol/L) dose-dependently inhibited the H2O2-induced increase in the level of cleaved caspase-9 but not of cleaved caspase-8. It also dose-dependently suppressed the H2O2-induced phosphorylation of JNK and ERK but not that of p38. CONCLUSION: Compound 6 isolated from the leaves of Gynura nepalensis potently protects H9c2 cardiomyoblasts against H2O2-induced apoptosis, possibly by inhibiting intrinsic apoptosis and the ERK/JNK pathway.

A novel caffeoyl triterpene attenuates cerebral ischemic injury with potent anti-inflammatory and hypothermic effects.

Despite the intense efforts in searching for stroke therapies, an urgent need still exists to explore novel neuroprotective agents for ischemic stroke that have high efficacy and wide therapeutic time-window. Here, we provide the first demonstration that 28-O-caffeoyl betulin (B-CA), a novel derivative of naturally occurring caffeoyl triterpene, could significantly alleviate brain infarction and neurological deficit when given as late as 6 h after transient middle cerebral artery occlusion in the rat. Moreover, post-ischemia B-CA administration exhibited long-term (14 days post stroke) protective effects on both brain infarction and functional (i.e., motor and sensory) deficits. Protective B-CA effects correlated with decreased inflammatory responses as indicated by inhibition of microglia and astrocyte activation [stained with ionized calcium-binding adapter molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP) antibody, respectively], as well as suppression of tumor necrosis factor-α, interleukin-1ß, and cyclooxygenase-2 overproduction in the ipsilateral cortex of ischemic rat. B-CA administration caused significant hypothermia in the focal cerebral ischemic rat, which may contribute to its ameliorative effects on brain damage and inflammation. In view of its potency in wide therapeutic time-window, robust anti-inflammatory and hypothermic effects, this novel caffeoyl triterpene derivative may lead toward the development of effective therapeutic strategies for the treatment of ischemic stroke.

PTP1B inhibitors from stems of Angelica keiskei (Ashitaba).

Three new chalcones, xanthoangelols K-M (1-3), together with 19 known compounds were isolated from the stems of Angelica keiskei Koidzumi, a well-known rejuvenated and anti-diabetic plant originated from Japan. The structures of compounds 1-3 were elucidated on the basis of spectroscopic data and Mosher's method. All compounds were evaluated for their inhibitory activity against protein tyrosine phosphatase 1B (PTP1B). Among them, six chalcones, xanthoangelol K (1), xanthoangelol (4), xanthoangelol F (5), 4-hydroxyderricin (6), xanthoangelol D (7), xanthoangelol E (8), and a coumarin, methoxsalen (17), showed strong PTP1B inhibitory effect with IC50 values of 0.82, 1.97, 1.67, 2.47, 3.97, 1.43, and 2.53µg/mL, respectively. A kinetic study revealed that compound 1 inhibited PTP1B with characteristics typical of a competitive inhibitor. Molecular docking simulations elucidated that ring B of 1 may anchor in a pocket of PTP1B and the molecule is stabilized by hydrogen bonds with Arg47, Asp48, and π-π interaction with Phe182 of PTP1B.

Bioactive C21 Steroidal Glycosides from the Roots of Cynanchum otophyllum That Suppress the Seizure-like Locomotor Activity of Zebrafish Caused by Pentylenetetrazole.

Six new C21 steroidal glycosides, cynotophyllosides A-F (1-6), together with 16 known compounds, were isolated from the roots of Cynanchum otophyllum. The structures of the new compounds were elucidated by spectroscopic analysis and chemical methods. The three major components, otophylloside F (15), otophylloside B (17), and rostratamine 3-O-ß-D-oleandropyranosyl-(1→4)-ß-D-cymaropyranosyl-(1→4)-ß-D-cymaropyranoside (18), suppressed the seizure-like locomotor activity caused by pentylenetetrazole in zebrafish. Preliminary structure-activity relation studies revealed that a pregnene skeleton with a C-12 ester group (ikemaoyl > cinnamoyl > hydroxy > p-hydroxybenzoyl) and a C-3 sugar chain consisting of three 2,6-dideoxysaccharide units is essential for this suppressive activity.