TRIP6 promotes neural stem cell maintenance through YAP-mediated Sonic Hedgehog activation.

In the adult mammalian brain, new neurons are continuously generated from neural stem cells (NSCs) in the subventricular zone (SVZ)-olfactory bulb (OB) pathway. YAP, a transcriptional co-activator of the Hippo pathway, promotes cell proliferation and inhibits differentiation in embryonic neural progenitors. However, the role of YAP in postnatal NSCs remains unclear. Here, we showed that YAP was present in NSCs of the postnatal mouse SVZ. Forced expression of Yap promoted NSC maintenance and inhibited differentiation, whereas depletion of Yap by RNA interference or conditional knockout led to the decline of NSC maintenance, premature neuronal differentiation, and collapse of neurogenesis. For the molecular mechanism, thyroid hormone receptor-interacting protein 6 (TRIP6) recruited protein phosphatase PP1A to dephosphorylate LATS1/2, therefore inducing YAP nuclear localization and activation. Moreover, TRIP6 promoted NSC maintenance, cell proliferation, and inhibited differentiation through YAP. In addition, YAP regulated the expression of the Sonic Hedgehog (SHH) pathway effector Gli2 and Gli1/2 mediated the effect of YAP on NSC maintenance. Together, our findings demonstrate a novel TRIP6-YAP-SHH axis, which is critical for regulating postnatal neurogenesis in the SVZ-OB pathway.

Design of Pentanary Mixed-Chalcogenides Ag2In2SiS6-xSex (x = 1, 2) Based on the Bucket Effect: Local Structural Difference and High-Performance Nonlinear-Optical Properties Realized by Partial Congener Substitution.

Noncentrosymmetric chalcogenides are promising candidates for infrared nonlinear-optical (NLO) crystals, and exploring high-performance ones is a hot topic and challengeable. Herein, the combination of AgQ4, InQ4, and SiQ4 (Q = S, Se) units with different S/Se ratios resulted in the discovery of the tetrahedral chalcogenides Ag2In2SiS4Se2 (1) and Ag2In2SiS5Se (2). They both crystallize in the monoclinic Cc space group with different local structures. Co-occupied S/Se sites only exist in 2, and the arrangement of [In2SiQ3] six-membered rings builds different helical chains and 3D [(In2SiQ6)2-]n polyanionic frameworks in 1 and 2. They show balanced NLO performances, including phase-matchable moderate NLO responses (0.7 and 0.5 × AGS) and enhanced laser-induced damage thresholds (4.5 and 5.1 × AGS). Theoretical calculations reveal that their NLO responses are predominantly contributed by the AgQ4 and InQ4 units.

KREP2S6 (RE = Sm, Gd, Tb, Dy): A Series of Polar Rare-Earth Thiophosphates with High Laser-Induced Damage Thresholds and Moderate Nonlinear-Optical Responses Synergistically Contributed by Isolated P2S6 Units and {[RE2S15]24-}∞ Layers.

As one of the potential candidates of nonlinear-optical (NLO) materials, rare-earth chalcophosphates have demonstrated promising properties. Here, KREP2S6 (RE = Sm, Gd, Tb, Dy) were synthesized using the facile RE2O3-B-S solid-state method. They crystallize with a monoclinic chiral P21 structure, and their layer structures are built by isolated ethane-like P2S6 dimers and RES8 bicapped trigonal prisms built {[RE2S15]24-}∞ layers. By comparing the structures with related ones, the change of the alkali metal or RE3+ ions can cause structural transformation. Their band gaps are tunable between 2.58 and 3.79 eV, and their powder samples exhibit good NLO properties. Theoretical calculations suggest that the NLO properties are mainly contributed by P2S6 units and {[RE2S15]24-}∞ layers synergistically, in which {[RE2S15]24-}∞ layers and P2S6 units dominate the contribution to the band gap and second-harmonic-generation response, respectively. This work enriches the application of rare-earth chalcophosphates as NLO materials.

High-performance monolayer MoS2nanosheet GAA transistor.

In this article, a 0.7 nm thick monolayer MoS2nanosheet gate-all-around field effect transistors (NS-GAAFETs) with conformal high-κmetal gate deposition are demonstrated. The device with 40 nm channel length exhibits a high on-state current density of ~410µAµm-1with a large on/off ratio of 6 × 108at drain voltage = 1 V. The extracted contact resistance is 0.48 ± 0.1 kΩµm in monolayer MoS2NS-GAAFETs, thereby showing the channel-dominated performance with the channel length scaling from 80 to 40 nm. The successful demonstration of device performance in this work verifies the integration potential of transition metal dichalcogenides for future logic transistor applications.

A nomogram for prediction of ERCP success in patients with bile duct leaks: a multicenter study.

BACKGROUND: Bile duct leaks (BDLs) are serious complications that occurs after hepatobiliary surgery and trauma, leading to rapid clinical deterioration. Endoscopic retrograde cholangiopancreatography (ERCP) is the first-line treatment for BDLs, but it is not clear which patients will respond to this therapy and which patients will require additional surgical intervention. The aim of our study was to explore the predictors of successful ERCP for BDLs. METHODS: A retrospective analysis was conducted using data from six centers' databases. All consecutive patients who were clinically confirmed as BDLs were included in the study. Collected data were demographics, disease severity, and ERCP procedure characteristics. Univariate and multivariate analysis were used to select independent predictive factors that affect the outcome of ERCP for BDLs, and a nomogram was established. Calibration and ROC curves were used to evaluate the models. RESULTS: Four hundred and forty-eight consecutive patients were clinically confirmed as BDLs and 347 were excluded. In the 101 patients included patients, clinical success was achieved in 78 patients (77.2%). In logistic multivariable regression, two independent factors were negatively associated with the success of ERCP: SIRS (OR, 0.183; 95% CI 0.039-0.864; P = 0.032) and high-grade leak (OR 0.073; 95% CI 0.010-0.539; P = 0.010). Two independent factors were positively associated with the success of ERCP: leak-bridging drainage (OR 4.792; 95% CI 1.08-21.21; P = 0.039) and cystic duct leak (OR 6.193; 95% CI 1.03-37.17; P = 0.046). The prediction model with these four factors was evaluated using a receiver-operating characteristic (ROC) curve, which demonstrated an area under the curve of 0.9351. The calibration curve showed that the model had good predictive accuracy. CONCLUSION: Leak-bridging drainage and cystic duct leak are positive predictors for the success of ERCP, while SIRS and high-grade leak are negative predictors. This prediction model with nomogram has good predictive ability and practical clinical value, and may be helpful in clinical decision-making and prognostication.

Large common bile duct stones in high-risk elderly patients: Immediate endoscopic stone removal or elective stone removal? A single-center retrospective study.

BACKGROUND AND OBJECTIVE: For high-risk elderly patients with chronic diseases, endoscopic stone removal for large common bile duct stones is associated with a high risk of adverse events and incomplete stone removal. The aim of this study was to investigate whether the treatment strategy of short-term biliary plastic stent placement followed by elective endoscopic stone removal is more effective and safer than immediate endoscopic stone removal. METHODS: The data of 262 high-risk elderly patients who received endoscopic retrograde cholangiopancreatography (ERCP) for large common bile duct (CBD) stones from 2017 to 2022 were retrospectively analyzed. The patients were divided into group A (immediate stone removal) and group B (stent drainage + elective stone removal). The baseline data of the 2 groups were matched 1:1 by propensity score matching. The stone clearance rate, ERCP procedure time, total hospital stay, and procedure-related adverse events were compared between the matched groups. In group B, stone size before and after stent placement, hospital stay, procedure time and adverse events of two ERCPs were compared. RESULTS: A total of 57 pairs of patients were successfully matched between the 2 groups. The stone clearance rate in group B was higher than that in group A (89.5% vs. 75.3, P = 0.049). The total hospital stay in group B was longer than that in group A (11.86 ± 3.912 d vs. 19.14 ± 3.176 d, P<0.001). The total adverse event rate in group A was higher than that in group B (29.8% vs. 12.3%, P = 0.005). The incidence of cholangitis/cholecystitis after ERCP was significantly higher in group A than in group B (7.0% vs. 0.9% P = 0.029). There was no significant difference in the incidence of post-ERCP pancreatitis, bleeding, pneumonia, and cardio-cerebrovascular events between the 2 groups. There were no perforation cases in either group. After plastic biliary stent placement in group B, the stone size was significantly smaller than before stent placement (1.59 ± 0.544 cm vs. 1.95 ± 0.543 cm, P < 0.001), and there was no significant difference in the total adverse event incidence between the two ERCP procedures (18.8% vs. 10.9%, P = 0.214). CONCLUSION: For high-risk elderly patients with large CBD stones, the treatment strategy involving temporary placement of plastic stent and elective endoscopic stone removal is safer and more effective than immediate stone removal.

Nanoscale Electronic Transparency of Wafer-Scale Hexagonal Boron Nitride.

Monolayer hexagonal boron nitride (hBN) has attracted interest as an ultrathin tunnel barrier or environmental protection layer. Recently, wafer-scale hBN growth on Cu(111) was developed for semiconductor chip applications. For basic research and technology, understanding how hBN perturbs underlying electronically active layers is critical. Encouragingly, hBN/Cu(111) has been shown to preserve the Cu(111) surface state (SS), but it was unknown how tunneling into this SS through hBN varies spatially. Here, we demonstrate that the Cu(111) SS under wafer-scale hBN is homogeneous in energy and spectral weight over nanometer length scales and across atomic terraces. In contrast, a new spectral feature─not seen on bare Cu(111)─varies with atomic registry and shares the spatial periodicity of the hBN/Cu(111) moiré. This work demonstrates that, for some 2D electron systems, an hBN overlayer can act as a protective yet remarkably transparent window on fragile low-energy electronic structure below.

Analysis of risk factors for post-endoscopic papillectomy bleeding.

BACKGROUND: Endoscopic papillectomy (EP) is an effective treatment for ampullary lesions but technically challenging because of anatomical specificities concerning the high rate of adverse events. Bleeding is one of the most feared complications and can be potentially life-threatening. AIM: To study the risk factors for bleeding after EP are presented with the goal of establishing preventive measures. METHODS: A total of 173 consecutive patients with ampullary lesions undergone EP from January 2006 to October 2020 were enrolled in this study. They were divided into a bleeding group and a non-bleeding group depending on whether postoperative bleeding occurred. Related factors were analyzed by univariate and multivariate logistics regression. RESULTS: Postoperative bleeding was experienced in 33 patients (19.07%). Multivariate analysis also identified intraoperative bleeding (OR: 4.38, 95% CI: 1.87-11.15, p = .001) and endoscopic closure (OR: 0.25, 95% CI: 0.10-0.58, p = .001) as independent factors significantly associated with bleeding after EP. Lesion size (≥3 cm) was shown as an independent factor significantly associated with intraoperative bleeding (OR: 4.25, 95% CI: 1.21-16.44, p = .028). CONCLUSIONS: This retrospective evaluation found that endoscopic closure was associated with reduced risk and intraoperative bleeding with increased risk of bleeding after EP. Lesion size may indirectly influence the risk of postoperative bleeding by increasing the risk of intraoperative bleeding.

Differences in susceptibility to chlorantraniliprole between Chilo suppressalis (Lepidoptera: Crambidae) and two dominant parasitic wasps collected from Sichuan Province, China.

Chilo suppressalis Walker (Lepidoptera: Crambidae) is one of the most destructive pests occurring in the rice-growing regions of Asia. Parasitoids, mainly egg parasitoids, have been of interest for several years even with practical used cases. Therefore, the potential impact of insecticides on natural enemies needs great attention. In this study, chlorantraniliprole was evaluated for its impact on C. suppressalis and two dominant parasitic wasps. Bioassays showed that chlorantraniliprole had negligible toxicity to Eriborus terebrans but was significantly toxic to Chelonus munakatae; the mortality exceeded 50% when the concentration reached 46.83 ng/cm2. Enzyme assays suggested that the significantly different carboxylesterase activity may be involved in the high-level detoxification metabolism of E. terebrans. According to the results of enzyme gene correlation analysis, P450s may be the dominant factor in the detoxification metabolism of C. munakatae. In addition, the ryanodine receptor C-terminus of C. suppressalis (CsRyR), C. munakatae (CmRyR) and E. terebrans (EtRyR) were successfully cloned. Different amino acids at resistance mutation I4758 M between susceptible C. suppressalis (I) and parasitic wasps (M) may be related to susceptibility differences. Simulated docking showed that CsRyR and CmRyR can interact with chlorantraniliprole but not EtRyR. More interaction forces were formed between CsRyR and chlorantraniliprole than CmRyR. Furthermore, a Pi-Pi T-shape formed between 73PHE in CsRyR and the benzene ring in chlorantraniliprole. These results indicated that both detoxification metabolism and the target site could mediate the susceptibility difference between C. suppressalis and its parasitic wasps.

Use of Capillary Electrophoresis Migration Position for the Presumptive Identification of Hemoglobin Variants Prevalent in China.

Capillary electrophoresis (CE) is increasingly being used to screen for hemoglobinopathies. We here report the migration position of hemoglobin (Hb) variants prevalent in China determined by CE. The CE migration position showed excellent precision and minor inter-individual variation. We conclude that the CE migration position can be used as a reliable indicator for identifying Hb variants and can also help to establish a well-characterized library of Hb variants for their refined presumptive identification.

Instantly Detecting Catalysts' Hot Spots Temperature In Situ during Photocatalysis by Operando Raman Spectroscopy.

Precisely detecting the catalysts' hot spots temperature in situ instantly during photocatalysis is a great challenge but extremely important for chemical reactions. However, no efficient method has been developed to instantly detect the hot spots temperature in situ during photocatalysis. Herein, we designed a simple and convenient method to measure the instant hot spots temperature in situ on the nanostructure surface during photocatalysis by operando Raman spectroscopy using 4-methoxyphenyl isocyanide (MI) as the probe molecule. The νN≡C frequency of MI varied linearly with temperature, which is caused by the orientation change of the MI induced by temperature, leading to the change in the frequency of the νN≡C bond that directly interacts with the nanostructure surface. Using in situ surface-enhanced Raman spectroscopy (SERS), the surface temperature of the catalysts illuminating for each time can be measured instantly. Interestingly, the catalytic activity of the hydrogen evolution reaction (HER) for the Au-Ag/Ag2S heterojunction nanorods (HJNRs) are higher than that for the Ag-Au-Ag HJNRs, although they have a lower surface temperature during photocatalysis; therefore, hot carriers and electronic structure contributed more to the catalytic activity of the Au-Ag/Ag2S HJNRs than that of the Ag-Au-Ag HJNRs. Such an instant hot spots temperature detecting method of catalysts can greatly facilitate the analysis of the mechanism of catalytic processes.

Ledge-directed epitaxy of continuously self-aligned single-crystalline nanoribbons of transition metal dichalcogenides.

Two-dimensional transition metal dichalcogenide nanoribbons are touted as the future extreme device downscaling for advanced logic and memory devices but remain a formidable synthetic challenge. Here, we demonstrate a ledge-directed epitaxy (LDE) of dense arrays of continuous, self-aligned, monolayer and single-crystalline MoS2 nanoribbons on ß-gallium (III) oxide (ß-Ga2O3) (100) substrates. LDE MoS2 nanoribbons have spatial uniformity over a long range and transport characteristics on par with those seen in exfoliated benchmarks. Prototype MoS2-nanoribbon-based field-effect transistors exhibit high on/off ratios of 108 and an averaged room temperature electron mobility of 65 cm2 V-1 s-1. The MoS2 nanoribbons can be readily transferred to arbitrary substrates while the underlying ß-Ga2O3 can be reused after mechanical exfoliation. We further demonstrate LDE as a versatile epitaxy platform for the growth of p-type WSe2 nanoribbons and lateral heterostructures made of p-WSe2 and n-MoS2 nanoribbons for futuristic electronics applications.

Synthesis, biological evaluation, and correlation of cytotoxicity versus redox potential of 1,4-naphthoquinone derivatives.

A series of 1,4-naphthoquinone derivatives of lawsone (1), 6-hydroxy-1,4-naphthoquinone (2), and juglone (3) were synthesized by alkylation, acylation, and sulfonylation reactions. The yields of lawsone derivatives 1a-1k (type A), 6-hydroxy-1,4-naphthoquinone derivatives 2a-2j (type B), and juglone derivatives 3a-3h (type C) were 52-99%, 53-96%, and 28-95%, respectively. All compounds were tested in vitro for the cytotoxicity against human oral epidermoid carcinoma (KB) and cervix epithelioid carcinoma (HeLa) cells and their structure-activity relationship was studied. Compound 3c was found to be most potent in KB cell line (IC50 = 1.39 µM). Some compounds were evaluated for DNA topoisomerase I inhibition. Compounds 2c, 3, 3a, and 3d showed topoisomerase inhibition activity with IC50 values of 8.3-91 µM. Standard redox potentials (E°) of all naphthoquinones in phosphate buffer at pH 7.2 were examined by means of cyclic voltammetry. A definite correlation has been found between the redox potentials and inhibitory effects of type A compounds.

Revealing the reason for the reversal of properties from fullerene to nonfullerene.

The existence of an inflection point between fullerene and nonfullerene molecules was demonstrated using bowl-nonfullerene models, which were proposed to explore the key points relating to the different properties. This study explains the differences in the stacking configurations of the inflection points and reveals the reason for the inversion of properties, which is caused by small structural differences.

Mechanisms for multiple resistances in field populations of rice stem borer, Chilo suppressalis (Lepidoptera: Crambidae) from Sichuan Province, China.

Chilo suppressalis Walker (Lepidoptera: Crambidae) is a widely destructive pest occurring in rice, particularly in the rice-growing regions of Asia. In recent years, C. suppressalis has developed resistance to several insecticides because of the extensive use of insecticides. The resistance levels to four insecticides were determined among populations from different regions of Sichuan Province, China, using a drop-method bioassay. Based on LC50 values of a laboratory susceptible strain, all field populations showed moderate level of resistance to triazophos (23.9- to 83.5-fold) and were either susceptible or had a low level of resistance to abamectin (2.1- to 5.8-fold). All field-collected populations had a low or moderate level of resistance to chlorpyrifos (1.7- to 47.1-fold) and monosultap (2.7- to 13.5-fold). The synergism experiment indicated that the resistance of the XW19 to triazophos may be associated with cytochrome P450 monooxygenases (P450s), with the highest synergistic ratio (SR) of 3.05-fold and increased ratio (IR) of 2.28-fold for piperonylbutoxide (PBO). The P450 activity of the TJ19 population was the greatest among the six field populations. Moreover, the relative expression levels of four resistance-related P450 genes were detected with qRT-PCR, and the results indicated that CYP324A12, CYP321F3 and CYP9A68 were overexpressed in the resistant population, especially in the XW19 population (by 1.2-, 3.4 -, and 18.0-fold, respectively). In addition, the relative expression levels of CYP9A68 among the CZ19 and TJ19 populations were also enhanced 10.5- and 24.9-fold, respectively. These results suggested that CYP324A12, CYP321F3 and CYP9A68 may be related to the resistance development of C. suppressalis to triazophos.

Nonvolatile molecular memory with the multilevel states based on MoS2 nanochannel field effect transistor through tuning gate voltage to control molecular configurations.

A new flexible memory element is crucial for mobile and wearable electronics. A new concept for memory operation and innovative device structure with new materials is certainly required to address the bottleneck of memory applications now and in the future. We report a new nonvolatile molecular memory with a new operating mechanism based on two-dimensional (2D) material nanochannel field-effect transistors (FETs). The smallest channel length for our 2D material nanochannel FETs was approximately 30 nm. The modified molecular configuration for charge induced in the nanochannel of the MoS2 FET can be tuned by applying an up-gate voltage pulse, which can vary the channel conductance to exhibit memory states. Through controlling the amounts of triggered molecules through either different gate voltage pulses or gate duration time, multilevel states were obtained in the molecular memory. These new molecular memory transistors exhibited an erase/program ratio of more than three orders of current magnitude and high sensitivity, of a few picoamperes, at the current level. Reproducible operation and four-level states with stable retention and endurance were achieved. We believe this prototype device has potential for use in future memory devices.

Sub-nanometre channels embedded in two-dimensional materials.

Two-dimensional (2D) materials are among the most promising candidates for next-generation electronics due to their atomic thinness, allowing for flexible transparent electronics and ultimate length scaling. Thus far, atomically thin p-n junctions, metal-semiconductor contacts, and metal-insulator barriers have been demonstrated. Although 2D materials achieve the thinnest possible devices, precise nanoscale control over the lateral dimensions is also necessary. Here, we report the direct synthesis of sub-nanometre-wide one-dimensional (1D) MoS2 channels embedded within WSe2 monolayers, using a dislocation-catalysed approach. The 1D channels have edges free of misfit dislocations and dangling bonds, forming a coherent interface with the embedding 2D matrix. Periodic dislocation arrays produce 2D superlattices of coherent MoS2 1D channels in WSe2. Using molecular dynamics simulations, we have identified other combinations of 2D materials where 1D channels can also be formed. The electronic band structure of these 1D channels offers the promise of carrier confinement in a direct-gap material and the charge separation needed to access the ultimate length scales necessary for future electronic applications.

Unraveling Spatially Heterogeneous Ultrafast Carrier Dynamics of Single-Layer WSe2 by Femtosecond Time-Resolved Photoemission Electron Microscopy.

Studies of the ultrafast carrier dynamics of transition metal dichalcogenides have employed spatially averaged measurements, which obfuscate the rich variety of dynamics that originate from the structural heterogeneity of these materials. Here, we employ femtosecond time-resolved photoemission electron microscopy (TR-PEEM) with sub-80 nm spatial resolution to image the ultrafast subpicosecond to picosecond carrier dynamics of monolayer tungsten diselenide (WSe2). The dynamics observed following 2.41 eV pump and 3.61 eV probe occurs on two distinct time scales. The 0.1 ps process is assigned to electron cooling via intervalley scattering, whereas the picosecond dynamics is attributed to exciton-exciton annihilation. The 70 fs decay dynamics observed at negative time delay reflects electronic relaxation from the Γ point. Analysis of the TR-PEEM data furnishes the spatial distributions of the various time constants within a single WSe2 flake. The spatial heterogeneity of the lifetime maps is consistent with increased disorder along the edges of the flake and the presence of nanoscale charge puddles in the interior. Our results indicate the need to go beyond spatially averaged time-resolved measurements to understand the influence of structural heterogeneities on the elementary carrier dynamics of two-dimensional materials.

New Hirsutinolide-Type Sesquiterpenoids from Vernonia cinerea Inhibit Nitric Oxide Production in LPS-Stimulated RAW264.7 Cells.

Phytochemical investigation of ethanol extracts from two Taiwanese collections of Vernonia cinerea resulted in the isolation of eighteen hirsutinolide-type sesquiterpenoids, including seven new ones designated as vernolides E - K (1: -7: ). All structures were determined by a combination of detailed spectroscopic analyses (NMR and MS) and comparison with reported data. In an in vitro anti-inflammatory assay, compounds 3, 7, 9, 11: , and 14: exhibited strong inhibitory activities toward NO production by LPS-induced RAW264.7 macrophages, with IC50 values of 1.18, 0.85, 0.66, 0.71 and 0.45 µM, respectively, without affecting cellular viability at 40 µM. Preliminary structure-activity relationships indicate that the ester groups at C-8 and C-13 may enhance inhibition of NO production.