Asymmetric Divergent Synthesis of ent-Kaurane-, ent-Atisane-, ent-Beyerane-, ent-Trachylobane-, and ent-Gibberellane-type Diterpenoids.

A unified strategy toward asymmetric divergent syntheses of nine C8-ethano-bridged diterpenoids A1-A9 (candol A, powerol, sicanadiol, epi-candol A, atisirene, ent-atisan-16α-ol, 4-decarboxy-4-methyl-GA12, trachinol, and ent-beyerane) has been developed based on late-stage transformations of common synthons having ent-kaurane and ent-trachylobane cores. The expeditious assembly of crucial advanced ent-kaurane- and ent-trachylobane-type building blocks is strategically explored through a regioselective and diastereoselective Fe-mediated hydrogen atom transfer (HAT) 6-exo-trig cyclization of the alkene/enone and 3-exo-trig cyclization of the alkene/ketone, showing the multi-reactivity of densely functionalized polycyclic substrates with πC═C and πC═O systems in HAT-initiated reactions. Following the rapid construction of five major structural skeletons (ent-kaurane-, ent-atisane-, ent-beyerane-, ent-trachylobane-, and ent-gibberellane-type), nine C8-ethano-bridged diterpenoids A1-A9 could be accessed in the longest linear 8 to 11 steps starting from readily available chiral γ-cyclogeraniol 1 and known chiral γ-substituted cyclohexenone 2, in which enantioselective total syntheses of candol A (A1, 8 steps), powerol (A2, 9 steps), sicanadiol (A3, 10 steps), epi-candol A (A4, 8 steps), ent-atisan-16α-ol (A6, 11 steps), and trachinol (A8, 10 steps) are achieved for the first time.

Exosomal Vaccine Loading T Cell Epitope Peptides of SARS-CoV-2 Induces Robust CD8+ T Cell Response in HLA-A Transgenic Mice.

Purpose: Current vaccines for the SARS-CoV-2 virus mainly induce neutralizing antibodies but overlook the T cell responses. This study aims to generate an exosomal vaccine carrying T cell epitope peptides of SARS-CoV-2 for the induction of CD8+ T cell response. Methods: Thirty-one peptides presented by HLA-A0201 molecule were conjugated to the DMPE-PEG-NHS molecules, and mixed with DSPE-PEG to form the peptide-PEG-lipid micelles, then fused with exosomes to generate the exosomal vaccine, followed by purification using size-exclusion chromatography and validation by Western blotting, liquid nuclear magnetic resonance (NMR) test and transmission electron microscopy. Furthermore, the exosomal vaccine was mixed with Poly (I:C) adjuvant and subcutaneously administered for three times into the hybrid mice of HLA-A0201/DR1 transgenic mice with wild-type mice. Then, the epitope-specific T cell responses were detected by ex vivo ELISPOT assay and intracellular cytokine staining. Results: The exosomal vaccine was purified from the Peak 2 fraction of FPLC and injected into the hybrid mice for three times. The IFN-γ spot forming units and the frequencies of IFN-γ+/CD8+ T cells were 10-82-fold and 13-65-fold, respectively, higher in the exosomal vaccine group compared to the Poly (I:C) control group, without visible organ toxicity. In comparison with the peptides cocktail vaccine generated in our recent work, the exosomal vaccine induced significantly stronger T cell response. Conclusion: Exosomal vaccine loading T cell epitope peptides of SARS-CoV-2 virus was initially generated without pre-modification for both peptides and exosomes, and elicited robust CD8+ T cell response in HLA-A transgenic mice.

Iron(III)-catalyzed tandem annulation of indolyl-substituted p-quinone methides with ynamides for the synthesis of cyclopenta[b]indoles.

The unique reactivity of indolyl-substituted p-QMs as a new type of two-carbon synthon has been explored for the first time in a novel iron(III)-catalyzed tandem annulation. This (2+2) annulation/retro-4π electrocyclization/imino-Nazarov cyclization cascade reaction is characterized by an unusual structural reconstruction of indolyl-substituted p-QMs, leading to an expeditious assembly of synthetically important functionalized cyclopenta[b]indoles.

Seasonal variations in group leaf characteristics in species with red young leaves.

The leaves of many plants are red during particular stages of their lives, but the adaptive significance of leaf colouration is not yet clearly understood. In order to reveal whether anthocyanins play a similar role (i.e. antioxidants) in different seasonal contexts, this study investigated species with red young leaves in the subtropical forest of Dinghushan biosphere reserve (South China) during summer and winter and compared group leaf characteristics between the two seasons. Of 62 total species, 33 exhibited red young leaves in summer only, 6 in winter only, and 23 in both seasons. The anthocyanins extracted from most of these species had an absorption peak at ~530 nm. Frequency distribution analysis showed that the species containing anthocyanins at levels ranging from 0.02 to 0.04 µmol cm-2 occurred most frequently in summer or winter. Based on conditional grouping of the species, no significant variation was observed in the average anthocyanin contents and antioxidant abilities between summer and winter; the flavonoid content in summer was 2-fold that in winter, whereas the anthocyanin:flavonoid ratio in summer was only half that in winter. Moreover, a positive correlation between anthocyanins and flavonoids was found in summer. Therefore, it is less likely for anthocyanins to serve as antioxidants in summer than winter, because such a function in summer leaves is readily replaced by other flavonoids.

Low-Dimensional Perovskites with Diammonium and Monoammonium Alternant Cations for High-Performance Photovoltaics.

Low-dimensional Ruddlesden-Popper (LDRP) perovskites are a current theme in solar energy research as researchers attempt to fabricate stable photovoltaic devices from them. However, poor exciton dissociation and insufficiently fast charge transfer slows the charge extraction in these devices, resulting in inferior performance. 1,4-Butanediamine (BEA)-based low-dimensional perovskites are designed to improve the carrier extraction efficiency in such devices. Structural characterization using single-crystal X-ray diffraction reveals that these layered perovskites are formed by the alternating ordering of diammonium (BEA2+ ) and monoammonium (MA+ ) cations in the interlayer space (B-ACI) with the formula (BEA)0.5 MAn PbnI3n+1 . Compared to the typical LDRP counterparts, these B-ACI perovskites deliver a wider light absorption window and lower exciton binding energies with a more stable layered perovskite structure. Additionally, ultrafast transient absorption indicates that B-ACI perovskites exhibit a narrow distribution of quantum well widths, leading to a barrier-free and balanced carrier transport pathway with enhanced carrier diffusion (electron and hole) length over 350 nm. A perovskite solar cell incorporating BEA ligands achieves record efficiencies of 14.86% for (BEA)0.5 MA3 Pb3 I10 and 17.39% for (BEA)0.5 Cs0.15 (FA0.83 MA0.17 )2.85 Pb3 (I0.83 Br0.17 )10 without hysteresis. Furthermore, the triple cations B-ACI devices can retain over 90% of their initial power conversion efficiency when stored under ambient atmospheric conditions for 2400 h and show no significant degradation under constant illumination for over 500 h.

A magic red coat on the surface of young leaves: anthocyanins distributed in trichome layer protect Castanopsis fissa leaves from photoinhibition.

The presence of anthocyanins in young leaves plays an important role in mitigation against photodamage and allows leaves to grow and develop normally. Many studies have reported that foliar anthocyanins are distributed within the vacuoles of mesophyll cells, so we explored the novel defence style of anthocyanin-coated young leaves of Castanopsis fissa, a dominant subtropical forest tree species, via removable trichomes. Anthocyanins were distributed in C. fissa leaf trichomes, which produced a red coating for the young leaves. As young leaves developed and then matured, the thickness and density of the anthocyanin trichomes progressively decreased, the coating finally disappearing, allowing greater utilization of light by mature leaves. In addition to anthocyanins, the trichomes contained a remarkably high amount of phenolics, which enable the red coating to be more efficient in screening ultraviolet light. Compared with mature leaves, the young leaves exhibited lower photosynthetic ability, which was attributable to the reduced chlorophyll and Rubisco contents. Removal of the red coating had little effect on the photosynthetic capacity of young leaves. However, the young leaves without the coating suffered greater light-induced photoinhibition due to greater excess light entering the chloroplast and the production of H2O2 Our results suggest that the anthocyanin coating is photoprotective and this anthocyanin defence style may be a metabolically cost-effective way of adjusting the anthocyanin content in response to demand.

Reconstruction of Digital Skin Defects with the Free Wrist Crease Flap.

BACKGROUND: Soft-tissue digital defects frequently need to be covered by a flap rather than a skin graft. In hand surgery, functional preservation and aesthetic appearance are often as important as procedural efficacy. OBJECTIVE: We present our clinical experience with reconstruction of digital skin defects with the free wrist crease flap. METHODS: From January 2012 to September 2013, 14 digits of 14 patients (10 males, 4 females) were included for evaluation. The procedure was performed with brachial plexus block anesthesia. The superficial palmar branch of the radial artery, a subcutaneous superficial vein, and the palmar cutaneous branch of the median nerve were included in the free wrist crease flap. The flaps were used to reconstruct the skin defect of injured digits through microvascular anastomosis, and donor sites were closed primarily. RESULTS: Postoperative follow-up time ranged from 3 to 25 months. All digital deformities were corrected, all flaps survived completely without ischemia, and none were aesthetically bulky. The area of free wrist crease flaps ranged from 2.5 to 5.0 cm by 2.0 to 3.1 cm. Slight wound infections appeared in two cases. Venous crisis occurred in one case, but it was successfully addressed after vascular exploration and reanastomosis. Sensation determined by static two-point discrimination measured in these flaps 2 months postsurgery was "good" at a mean 9.7 ± 2.1 mm (range, 6-14 mm). The mean motion range of the distal interphalangeal joint and proximal interphalangeal joint was 23.4 ± 6.9 degrees (0-42 degrees) and 75.8 ± 22.1 degrees (0-98 degrees) preoperatively. The mean motion range of the distal interphalangeal joint recovered to 40.3 ± 5.7 degrees (36-42 degrees), and that of the proximal interphalangeal joint was 90.3 ± 15.3 degrees (85-98 degrees) postoperatively. Both joints reached normal motion angle and difference was statistically significant preoperatively and postoperatively (p < 0.05). The mean disabilities of arm and shoulder (DASH) score was 6.8 ± 3.4 (0-15), and there was statistically significant difference when compared with the preoperative score of 13.5 ± 4.3 (3-19) (p < 0.05). CONCLUSION: We found the free wrist crease flap to be an ideal solution for reconstruction of skin defects of digits.

A comparison of skin expansion and contraction between one expander and two expanders: a preliminary study.

BACKGROUND: This study aimed to compare the difference between the skin expansion and contraction rates for an expanded flap with one versus two expanders. METHODS: The study cohort comprised 24 cases of two overlapping expanders and 15 cases of a single implanted expander involving 22 patients. The method of "wet-cloth sampling" was applied to measure the expanded flap area and the initial unexpanded area and to calculate the skin expansion rate. Two points 5 cm apart in the center of the expanded flap were selected before the second surgical stage. After removal of the expander, the distance between the two fixed points was measured and recorded. The contraction rate of the expanded flap then was calculated. RESULTS: During the same period of expansion in the two groups (p = 0.06, >0.01), the skin expansion rate was 3.5 ± 0.9 % in the group with two overlapping expanders and 2.6 ± 0.6 % in the control group. The difference between the two groups was statistically significant (p = 0.002, <0.05). The instantly expanded flap contraction rates were 30.3 ± 0.8 and 32.3 ± 0.9 %, respectively for the two groups, and the difference was not statistically significant (p = 0.47, >0.05). We fitted a linear regression model that was Y = 0.533 − 0.003X, where Y was the contraction rate of the expanded flap and X was the period of expansion. The contraction rate of the expanded flap was negatively correlated with the period of expansion. CONCLUSIONS: Compared with the traditional method of implanting a single expander, the new method of overlapping two expanders in a single cavity increased the skin expansion rate. The instantly expanded flap contraction rate did not differ significantly between the two groups, so the amount of expanded skin area absolutely increased. The clinical application of the new method is worth promoting. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Impact of committed individuals on vaccination behavior.

We study how the presence of committed vaccinators, a small fraction of individuals who consistently hold the vaccinating strategy and are immune to influence, impact the vaccination dynamics in well-mixed and spatially structured populations. For this purpose, we develop an epidemiological game-theoretic model of a flu-like vaccination by integrating an epidemiological process into a simple agent-based model of adaptive learning, where individuals (except for those committed ones) use anecdotal evidence to estimate costs and benefits of vaccination. We show that the committed vaccinators, acting as "steadfast role models" in the populations, can efficiently avoid the clustering of susceptible individuals and stimulate other imitators to take vaccination, hence contributing to the promotion of vaccine uptake. We substantiate our findings by making comparative studies of our model on a full lattice and on a randomly diluted one. Our work is expected to provide valuable information for decision-making and design more effective disease-control strategy.

Generic and rapid determination of veterinary drug residues and other contaminants in raw milk by ultra performance liquid chromatography-tandem mass spectrometry.

A generic, rapid and simple analytical method able to identify 255 veterinary drug residues and other contaminants in raw milk had been developed. The method was based on two-step simple precipitation and ultra performance liquid chromatography coupled with electrospray ionization and tandem mass spectrometry (UPLC-ESI-MS/MS) operating both in positive and negative multiple reaction mode (MRM). For most of the target analytes, the optimized pretreatment processes led to no significant interference on analysis from complicated sample matrix. For quantification, matrix-fortified calibration curves were performed to compensate for the matrix effect and loss in sample preparation. Competent linearity was found for over 90% of target compounds with linear regression coefficients (R) higher than 0.99. Detection limits ranged from 0.05 to 10µg/kg. Average recoveries spiked into raw milk were in the range from 63% to 141% with associated RSD values from 1% to 29% under the selected conditions. The method had been validated for its extraction sensitivity, linearity, recoveries and precision. The results clearly demonstrated the feasibility of the approach proposed. Application of this method, which improved efficiency and coverage of residues, would imply a drastic reduction of both effort and time in routine monitoring programs.

[Epidemiology and related factor analysis of visual fatigue in university students of Haidian District of Beijing].

OBJECTIVE: To analyze and explore the epidemiological characteristicss and related factors for visual fatigue among university students in Haidian District of Beijing. METHODS: The investigation with questionnaires was conducted in 2 246 undergraduates and postgraduates from four universities in Haidian District by multi-level stratified cluster sampling. Factor analysis and multivariate Logistic regression model were conducted to explore the related factors for visual fatigue. RESULTS: Among the university students, the total prevalence rate of visual fatigue was 64.9%, and the prevalence rates of males, females, undergraduates and postgraduates were 65.1%, 64.7%, 58.9% and 75.7%, respectively. The result of multivariate logistic regression analysis showed that bad living environment conditions, improper computer use and bad health status were significantly associated with increased risk of visual fatigue, the ORs (95% CI) were 1.185 (1.078, 1.302), 1.490 (1.355, 1.640) and 1.323 (1.182, 1.481), respectively; good sleep and mental status, good psycho-social state, and good factors of habits and diets might be protective against visual fatigue, the ORs (95% CI) were 0.691 (0.628, 0.760), 0.793 (0.720, 0.873) and 0.649 (0.587, 0.717), respectively. CONCLUSION: The university students showed higher prevalence rate of visual fatigue. Psychological state, environment, health status, diets and habits were related to the development of visual fatigue. Health education should be strengthened among university students to prevent the adverse effects of visual fatigue on their health.

One-pot highly efficient synthesis of substituted pyrroles and N-bridgehead pyrroles by zinc-catalyzed multicomponent reaction.

A convenient zinc(II) chloride-catalyzed regioselective propargylation/amination/cycloisomerization process has been developed for the synthesis of substituted pyrrole derivatives from propargylic acetates, enoxysilanes and primary amines. Various aromatic and aliphatic propargylic acetates participate well in the reaction, providing the propargylation/amination/cycloisomerization products in good yields with complete regioselectivity. The one-pot multicomponent coupling reaction furnishes substituted pyrroles in high yields by circumventing the intermediates' isolation. Zinc(II) chloride acts as a multifunctional catalyst and catalyzes three mechanistically distinct processes in a single-pot. The protocol developed has been extended to the synthesis of N-bridgehead pyrroles containing polycyclic fragments.