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Yi Zhang,1– 3 Bo Zhou,1,2,4 Min Wen,1 Mi Hu,1 Jin-Gang Peng,1– 3 Ying Wang,3 Lin-Lin Fan,1– 3 Lei Tang1– 3 1College of Basic Medical Sciences, Guizhou Medical University, Guizhou, 550004, People’s Republic of China; 2Engineering Technology Research Center for Chemical Drug R&D, Guizhou 550004, People’s Republic of China; 3College of Pharmacy, Guizhou Medical University, Guizhou 550004, People’s Republic of China; 4State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guizhou 550004, People’s Republic of ChinaCorrespondence: Lei Tang Tel +86 13308500332Email tlei1974@gmc.edu.cnPurpose: The aim of the present study was to investigate the hypoglycemic activity and potential mechanism of tetrahydrocarbazole derivatives ZG02 in high-fat diet/streptozotocin-induced type 2 diabetes model.Methods: C57BL/6 mice (n=30) were randomly assigned to three groups: control group (n=10) was fed with normal diet, the diabetes group (n=10) was fed with high-fat diet for eight weeks followed by intraperitoneal injection of streptozotocin (25 mg/kg) and the ZG02 group (n=10) injected intraperitoneally with ZG02 (30 mg/kg/day) for two weeks after successful modeling. The changes of weight, fasting blood glucose, oral glucose tolerance and fasting blood insulin levels in each group were evaluated. In addition, we also assessed the expression level of total AMPK, phosphorylation AMPK, SIRT1, PGC-1 and the activity of G6PC in liver.Results: The results demonstrated that ZG02 could significantly antagonize the high-fat diet/streptozotocin-induced fasting hyperglycemia, restore fasting blood insulin levels and also improve activity of G6PC in liver. The results from Western blot indicated that ZG02 significantly restored the expression level of phosphorylation AMPK, Sirt1 and PGC-1.Conclusion: ZG02 improve hepatic glucose metabolism and insulin sensitivity via activation AMPK/Sirt1 signaling pathways in type 2 diabetes mice model.Keywords: type 2 diabetes, glucose metabolism, ZG02, AMPK, high fat

Main Conclusion: The post-transcriptional gene regulatory pathway and small RNA pathway play important roles in regulating the rapid and long-term response of Rhododendron moulmainense to high-temperature stress. The Rhododendron plays an important role in maintaining ecological balance. However, it is difficult to domesticate for use in urban ecosystems due to their strict optimum growth temperature condition, and its evolution and adaptation are little known. Here, we combined transcriptome and small RNAome to reveal the rapid response and long-term adaptability regulation strategies in Rhododendron moulmainense under high-temperature stress. The post-transcriptional gene regulatory pathway plays important roles in stress response, in which the protein folding pathway is rapidly induced at 4 h after heat stress, and alternative splicing plays an important role in regulating gene expression at 7 days after heat stress. The chloroplasts oxidative damage is the main factor inhibiting photosynthesis efficiency. Through WGCNA analysis, we identified gene association patterns and potential key regulatory genes responsible for maintaining the ROS steady-state under heat stress. Finally, we found that the sRNA synthesis pathway is induced under heat stress. Combined with small RNAome, we found that more miRNAs are significantly changed under long-term heat stress. Furthermore, MYBs might play a central role in target gene interaction network of differentially expressed miRNAs in R. moulmainense under heat stress. MYBs are closely related to ABA, consistently, ABA synthesis and signaling pathways are significantly inhibited, and the change in stomatal aperture is not obvious under heat stress. Taken together, we gained valuable insights into the transplantation and long-term conservation domestication of Rhododendron, and provide genetic resources for genetic modification and molecular breeding to improve heat resistance in Rhododendron., (© 2024. The Author(s).)

Background: The diagnostic criteria for Parkinson's disease (PD) remain complex, which is especially problematic for nonmovement disorder experts. A test is required to establish a diagnosis of PD with improved accuracy and reproducibility., Objective: The study aimed to investigate the sensitivity and specificity of tests using sniffer dogs to diagnose PD., Methods: A prospective, diagnostic case-control study was conducted in four tertiary medical centers in China to evaluate the accuracy of sniffer dogs to distinguish between 109 clinically established medicated patients with PD, 654 subjects without PD, 37 drug-naïve patients with PD, and 185 non-PD controls. The primary outcomes were sensitivity and specificity of sniffer dog's identification., Results: In the study with patients who were medicated, when two or all three sniffer dogs yielded positive detection results in a sample tested, the index test sensitivity, specificity, and positive and negative likelihood ratios were 91% (95% CI: 84%-96%), 95% (95% CI: 93%-97%), and 19.16 (95% CI: 13.52-27.16) and 0.10 (95% CI: 0.05-0.17), respectively. The corresponding sensitivity, specificity, and positive and negative likelihood ratios in patients who were drug-naïve were 89% (95% CI: 75%-96%), 86% (95% CI: 81%-91%), and 6.6 (95% CI: 4.51-9.66) and 0.13 (95% CI: 0.05-0.32), respectively., Conclusions: Tests using sniffer dogs may be a useful, noninvasive, fast, and cost-effective method to identify patients with PD in community screening and health prevention checkups as well as in neurological practice. © 2022 International Parkinson and Movement Disorder Society., (© 2022 International Parkinson and Movement Disorder Society.)

Four series of cajanonic acid A (CAA) derivatives have been designed and synthesized. The newly prepared compounds have been screened for glucose consumption activity in HepG2 cell lines and PPARγ antagonistic activity in HEK293 cell lines. Compound 26g bearing a tetrahydroisoquinolinone scaffold showed the most potent PPARγ antagonistic and hypoglycemic activities. An oral glucose tolerance test (OGTT) was performed and the results further confirmed that 26g was a potent hypoglycemic agent. In addition, the possible binding modes for compound 26g in the PPARγ protein have been investigated in this study., (Copyright © 2021. Published by Elsevier Ltd.)

We demonstrate the rapid photodarkening (PD) phenomenon in Tm-doped fiber (TDF) core pumped by a laser at 1080 nm and the bleaching effect of deuterium (${{\rm D}_2}$D 2 ) on PD TDF. By ${{\rm D}_2}$D 2 loading for seven days, the PD-induced excess loss (PIEL) in the visible (VIS) and near-infrared (NIR) region have been largely eliminated, and no degradation was observed within 30 days. PD resistance of the ${{\rm D}_2}$D 2 pretreated TDF has been investigated as well. The formation of color centers based on defects and precursors in the silica matrix and the mechanism of ${{\rm D}_2}$D 2 bleaching are discussed.

Four series of berberine derivatives were designed and synthesized. All the synthetic compounds were screened for in vitro glucose consumption activity in HepG2 cell lines. The results showed that most of the tested compounds exhibited potent hypoglycemic activity, and the most potent compound 20b exhibited its potency by 3.23-fold of berberine, 1.39-fold of metformin and 1.20-fold of rosiglitazone, respectively. Western blot assay indicated these novel berberine-based derivatives executed their glucose-decreasing activity via the activation of AMPK pathway., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The laser performance of a high-power ytterbium-doped fiber amplifier is mainly hindered by the onset of mode instability. In this work, the slope efficiency and mode instability threshold of the ytterbium-doped fiber under various gamma-ray radiation doses have been measured. Experimental results reveal that gamma-ray radiation-induced photodarkening degrades mode instability severely, and gamma-ray radiation-induced mode instability degradation can be partly bleached by hours of pump-light injection. It is shown that gamma-ray radiation-induced photodarkening results in a steep reduction of slope efficiency and mode instability threshold; moreover, the entire irradiated fiber can be partly bleached by hours of pump-light injection and exhibits both time and gamma-ray radiation-dose saturation properties. The experimental results indicate that mode instability mitigation can be partly realized by pump-light injection and implies photodarkening suppression is beneficial for TMI mitigation, which is very promising for the advancement of high-power fiber lasers.

We demonstrate the almost complete 2 µm laser power recovery of the gamma-ray-irradiated thulium (Tm)-doped silica fiber under deuterium loading. The optical-optical slope efficiency and the cladding absorption spectra of the Tm-doped fiber with gamma-ray irradiation and deuterium treatment have been measured for comparison. It was found that the slope efficiency of the irradiated Tm-doped fiber could be recovered to 96.1% of the pristine after deuterium bleaching, which significantly degraded from 60.7% to 25.3% after irradiation. Meanwhile, the additional absorption attenuation of the irradiated Tm-doped with D 2 treatment completely vanished. Based on the comprehensive comparison of cladding absorption spectra, the probable mechanism of the deuterium bleaching effect on irradiated Tm-doped fiber has also been discussed.

According to Ming's classification, gastric cancer (GC) can be divided into two types: expanding and infiltrative. The two types are readily recognizable by histology: expanding carcinomas grow en masse and by expansion, resulting in the formation of discrete tumour nodules, whereas in infiltrative carcinoma, tumour cells invade individually. Both types show varying degrees of cell maturation. The two types of carcinomas have vastly different pathological and clinical features. However, little is known concerning the mechanisms underlying these differences since no GC cell line models are available. For comprehensive and insightful analyses of mechanisms and treatment methods, new cell lines derived from expanding- and infiltrative-type gastric tumours are urgently needed. In the present study, we established an expanding-type GC cell line from a 72-year-old male patient. Different in vitro and in vivo methods were used to characterize the phenotypes of this cell line. This GC cell line was named XGC-2 and had an ~60 h doubling time. The cell line displayed strong colony formation and tumourigenicity in nude mice and had complicated chromosomal abnormalities. XGC-2 cells showed some markers of epithelial-to-mesenchymal transition (EMT), with decreased E-cadherin expression levels and increased vimentin expression levels. The XGC-2 cell line may be useful for future studies of GC development, progression, metastasis and therapy.

We report on the strong photo-bleaching of the photo-darkening (PD) induced loss under the cladding pump of a 793 nm laser diode (LD) in double clad Yb-doped fibers. Up to 68% PD loss at 810 nm was bleached. The bleaching rates under different powers show that the higher pump power corresponds to the more bleached loss within the same time. Moreover, repeatable processes of PD and photo-bleaching were observed when alternately pumped with 915 and 793 nm LDs. Furthermore, it was found that simultaneously pumping the fiber with 915 and 793 nm LDs can suppress about 80% PD loss, compared with pumping the fiber only with 915 nm LD. The mechanism of photo-bleaching under 793 nm pump was also discussed.

Tm-doped fiber laser or amplifier can be applied in varied adverse environments. In this work, we demonstrate the pump bleaching of Tm-doped silica fiber with 793nm pump source under gamma-ray irradiation in the range 50Gy-675Gy. The recovery time, the fiber slope efficiency and the fiber cladding absorption spectra after irradiation and bleaching have been measured. It is found that the recovery time and radiation induce absorption are positively associated with doses, however, the fiber slope efficiency of irradiated TDF and bleached TDF are both negatively correlated with doses. Based on the simulation of the fiber core temperature, the probable mechanism of pump bleaching is also discussed.

Unlabelled: Interaction between E and prM proteins in flavivirus-infected cells is a major factor for virus-like particle (VLP) production. The prM helical (prM-H) domain is topologically close to and may interact with domain II of the E protein (EDII). In this study, we investigated prM-H domain amino acid residues facing Japanese encephalitis virus EDII using site-directed mutagenesis to determine their roles in prM-E interaction and VLP production. Our results indicate that negatively charged prM-E125 residue at the prM-H domain affected VLP production via one or more interactions with positively charged E-K93 and E-H246 residues at EDII. Exchanges of oppositely charged residue side chains at prM-E125/E-K93 and prM-E125/E-H246 are recoverable for VLP production. The prM-E125 and E-H246 residues are conserved and that the positive charge of the E-K93 residue is preserved in different flavivirus groups. These findings suggest that the electrostatic attractions of prM-E125, E-K93, and E-H246 residues are important to flavivirus VLP production and that inhibiting these interactions is a potential strategy for blocking flavivirus infections., Importance: Molecular interaction between E and prM proteins of Japanese encephalitis virus is a major driving force for virus-like particle (VLP) production. The current high-resolution structures available for prM-E complexes do not include the membrane proximal stem region of prM. The prM stem region contains an N-terminal loop and a helix domain (prM-H). Since the prM-H domain is topologically close to domain II of the E protein (EDII), this study was to determine molecular interactions between the prM-H domain and EDII. We found that the molecular interactions between prM-E125 residue and positively charged E-K93 and E-H246 residues at EDII are critical for VLP production. More importantly, the prM-E125 and E-H246 residues are conserved and the positive charge of the E-K93 residue is preserved in different flavivirus groups. Our findings help refine the structure and molecular interactions on the flavivirus surface and reveal a potential strategy for blocking flavivirus infections by inhibiting these electrostatic interactions., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

Knowledge of virulence and immunogenicity is important for development of live-attenuated dengue vaccines. We previously reported that an infectious clone-derived dengue type 4 virus (DENV-4) passaged in MRC-5 cells acquired a Glu345Lys (E-E345K) substitution in the E protein domain III (E-DIII). The same cloned DENV-4 was found to yield a single E-Glu327Gly (E-E327G) mutation after passage in FRhL cells and cause the loss of immunogenicity in rhesus monkeys. Here, we used site-directed mutagenesis to generate the E-E345K and E-E327G mutants from DENV-4 and DENV-4Δ30 infectious clones and propagated in Vero or MRC-5 cells. The E-E345K mutations were consistently presented in viruses recovered from MRC-5 cells, but not Vero cells. Recombinant E-DIII proteins of E345K and E327G increased heparin binding correlated with the reduced infectivity by heparin treatment in cell cultures. Different from the E-E327G mutant viruses to lose the immunogencity in rhesus monkeys, the E-E345K mutant viruses were able to induce neutralizing antibodies in rhesus monkeys with an almost a 10-fold lower level of viremia as compared to the wild type virus. Monkeys immunized with the E-E345K mutant virus were completely protected with no detectable viremia after live virus challenges with the wild type DENV-4. These results suggest that the E-E345K mutant virus propagated in MRC-5 cells may have potential for the use in live-attenuated DENV vaccine development.

Coat color in dog breeds is an excellent character for revealing the power of artificial selection, as it is extremely diverse and likely the result of recent domestication. Coat color is generated by melanocytes, which synthesize pheomelanin (a red or yellow pigment) or eumelanin (a black or brown pigment) through the pigment type-switching pathway, and is regulated by three genes in dogs: MC1R (melanocortin receptor 1), CBD103 (β-defensin 103), and ASIP (agouti-signaling protein precursor). The genotypes of these three gene loci in dog breeds are associated with coat color pattern. Here, we resequenced these three gene loci in two Kunming dog populations and analyzed these sequences using population genetic approaches to identify evolutionary patterns that have occurred at these loci during the recent domestication and breeding of the Kunming dog. The analysis showed that MC1R undergoes balancing selection in both Kunming dog populations, and that the Fst value for MC1R indicates significant genetic differentiation across the two populations. In contrast, similar results were not observed for CBD103 or ASIP. These results suggest that high heterozygosity and allelic differences at the MC1R locus may explain both the mixed color coat, of yellow and black, and the difference in coat colors in both Kunming dog populations.

A GeO2 doped triangular-core photonic-crystal fiber (PCF) is designed and fabricated to allow the generation of a hollow beam through a nonlinear-optical transformation by femtosecond pulses at 1040 nm from a high power Yb-doped PCF laser oscillator. The hollow beam supercontinuum is obtained at far field by adjusting incident light polarization to excite the high order supermode, behaving as a mode convertor. The supercontinuum ranging from 540 to 1540 nm is achieved with an average power of 1.04 W.

The interaction between prM and E proteins in flavivirus-infected cells is a major driving force for the assembly of flavivirus particles. We used site-directed mutagenesis to study the potential role of the transmembrane domains of the prM proteins of Japanese encephalitis virus (JEV) in prM-E heterodimerization as well as subviral particle formation. Alanine insertion scanning mutagenesis within the GXXXG motif in the first transmembrane segment of JEV prM protein affected the prM-E heterodimerization; its specificity was confirmed by replacing the two glycines of the GXXXG motif with alanine, leucine and valine. The GXXXG motif was found to be conserved in the JEV serocomplex viruses but not other flavivirus groups. These mutants with alanine inserted in the two prM transmembrane segments all impaired subviral particle formation in cell cultures. The prM transmembrane domains of JEV may play importation roles in prM-E heterodimerization and viral particle assembly.

We studied a method of heat-assisted magnetic recording (HAMR). The recording medium is a strongly coupled Co/Pt multilayered thin film, suitable for perpendicular recording. Field emission current from a scanning tunneling microscope (STM) tip is used as the heating source. Pulse voltages of 5 V were applied to the film. Experimental results show that an average mark size of 100-120 nm was achieved, with the minimum being 45 nm. Models of domain stability and dynamic domain formation are built to quantitatively explain the experimental results. They agree well with experiments. The models give us future directions for achieving small marks for ultra-high recording density.