VAMP726 and VAMP725 regulate vesicle secretion and pollen tube growth in Arabidopsis.

KEY MESSAGE: VAMP726/VAMP725 and SYP131 can form a part of a SNARE complex to mediate vesicle secretion at the pollen tube apex. Secretory vesicle fusion with the plasma membrane of the pollen tube tip is a key step in pollen tube growth. Membrane fusion was mediated by SNAREs. However, little is known about the composition and function of the SNARE complex during pollen tube tip growth. In this study, we constructed a double mutant vamp725 vamp726 via CRISPR‒Cas9. Fluorescence labeling combined with microscopic observation, luciferase complementation imaging, co-immunoprecipitation and GST pull-down were applied in the study. We show that double mutation of the R-SNAREs VAMP726 and VAMP725 significantly inhibits pollen tube growth in Arabidopsis and slows vesicle exocytosis at the apex of the pollen tube. GFP-VAMP726 and VAMP725-GFP localize mainly to secretory vesicles and the plasma membrane at the apex of the pollen tube. In addition, fluorescence recovery after photobleaching (FRAP) experiments showed that mCherry-VAMP726 colocalizes with Qa-SNARE SYP131 in the central region of the pollen tube apical plasma membrane. Furthermore, we found that VAMP726 and VAMP725 can interact with the SYP131. Based on these results, we suggest that VAMP726/VAMP725 and SYP131 can form a part of a SNARE complex to mediate vesicle secretion at the pollen tube apex, and vesicle secretion may mainly occur at the central region of the pollen tube apical plasma membrane.

Mid-infrared carbon isotope spectrum logging system combined with a thermostat of optical subsystem for high-precision detection of isotope ratio.

In the process of oil and gas exploration and development, carbon isotope ratio can reflect the maturity of oil and gas and predict the recovery factor, and the isotope ratio in the composition of shale gas is particularly important. Thus, a carbon isotope spectrum logging system was designed and exploited based on tunable diode laser absorption spectroscopy (TDLAS) technology under the fundamental frequency absorption band of 12CO2 and 13CO2 molecules, and a quantum cascade laser (QCL) with center wavelength of 4.35 µm was applied. For further detection sensitivity, wavelength modulation spectroscopy (WMS) technology was combined to suppress background noise through the modulation of QCL. A multi-pass gas cell (MPGC) with an optical path length of 41 m was utilized for lower limit of detection (LoD). In order to suppress the temperature dependence of the absorption spectrum, the optical subsystem was placed in a high-precision thermostat to maintain a stable temperature, so as to achieve high-precision and high-stability detection. Meanwhile, sparrow search algorithm-back propagation (SSA-BP) was applied for concentration prediction of 12CO2 and 13CO2. Taking advantage of the excellent optimization ability, fast convergence speed and high stability of SSA, the problem that BP neural network algorithm is highly dependent on initial value can be solved to some extent. Sensor performance was validated through calibration and stability experiments. The LoD of 12CO2 reached a minimum of 0.618 parts-per-billion (ppb) with an 88 s averaging time, and the LoD of 13CO2 reached 0.181 ppb when the averaging time was 96 s. Besides, the standard deviation of carbon isotope ratio obtained by this system was âˆ¼ 0.61 ‰. The results illustrate that this self-developed sensor has a bright prospect in the field of shale gas isotope detection.

Synchronous enhancement of upconversion and NIR-IIb photoluminescence of rare-earth nanoprobes for theranostics.

This study develops a multifunctional molecular optical nanoprobe (SiO2@Gd2O3: Yb3+/Er3+/Li+@Ce6/MC540) with a unique core-satellite form. The rare-earth doped nanodots with good crystallinity are uniformly embedded on the surface of a hydrophilic silica core, and the nanoprobe can emit near-infrared-IIb (NIR-IIb) luminescence for imaging as well as visible light that perfectly matches the absorption bands of two included photosensitizers under 980 nm irradiation. The optimal NIR-IIb emission and upconversion efficiency are attainable via regulating the doping ratios of Yb3+, Er3+ and Li+ ions. The relevant energy transfer mechanism was addressed theoretically that underpins rare-earth photoluminescence where energy back-transfer and cross relaxation processes play pivotal roles. The nanoprobe can achieve an excellent dual-drive photodynamic treatment performance, verified by singlet oxygen detections and live-dead cells imaging assays, with a synergistic effect. And a brightest NIR-IIb imaging was attained in tumoral site of mouse. The nanoprobe has a high potential to serve as a new type of optical theranostic agent for tumor.

Optical Properties of a CsMnBr3 Single Crystal.

Lead-free perovskite materials with good stability are promising for various applications. In order to explore their application in optoelectronic devices, it is essential to investigate their fundamental optical properties. In this work, we have synthesized a CsMnBr3 single crystal (SC) with red emission at ∼621 nm and studied their optical properties. Through the measurement of temperature-dependent photoluminescence (PL) spectra, it is found that a phase transition occurs at approximately 100 K in the SC, which is absent in the CsMnBr3 nanocrystals (NCs). Furthermore, the SC exhibits stronger electron and longitudinal optical phonon coupling strength than that of the NCs at low temperatures. In addition, under the resonant excitation at 600 nm, the SC possesses strong saturable absorption property, with a modulation depth of ∼27%. Interestingly, the SC also exhibits a large two-photon absorption coefficient of ∼0.035 cm GW-1 at 800 nm and an excellent optical limiting behavior. The experimental results indicate that the CsMnBr3 SC is a class of excellent environmentally friendly optoelectronic materials.

Piperlongumine Inhibits Titanium Particles-Induced Osteolysis, Osteoclast Formation, and RANKL-Induced Signaling Pathways.

Wear particle-induced aseptic loosening is the most common complication of total joint arthroplasty (TJA). Excessive osteoclast formation and bone resorptive activation have been considered to be responsible for extensive bone destruction and prosthesis failure. Therefore, identification of anti-osteoclastogenesis agents is a potential therapy strategy for the treatment of aseptic loosening and other osteoclast-related osteolysis diseases. In the present study, we reported, for the first time, that piperlongumine (PL), a key alkaloid compound from Piper longum fruits, could significantly suppress the formation and activation of osteoclasts. Furthermore, PL effectively decreased the mRNA expressions of osteoclastic marker genes such as tartrate-resistant acid phosphatase (TRAP), calcitonin receptor (CTR), and cathepsin K (CTSK). In addition, PL suppressed the receptor activator of nuclear factor-κB ligand (RANKL)-induced activations of MAPKs (ERK, JNK and p38) and NF-κB, which down-regulated the protein expression of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1). Using a titanium (Ti) particle-induced calvarial osteolysis model, we demonstrated that PL could ameliorate Ti particle-induced bone loss in vivo. These data provide strong evidence that PL has the potential to treat osteoclast-related diseases including periprosthetic osteolysis (PPO) and aseptic loosening.

Tomatidine Suppresses the Destructive Behaviors of Fibroblast-Like Synoviocytes and Ameliorates Type II Collagen-Induced Arthritis in Rats.

Fibroblast-like synoviocytes (FLSs) are the prominent non-immune cells in synovium and play a pivotal role in rheumatoid arthritis (RA) pathogenesis. Searching for natural compounds that may suppress the pathological phenotypes of FLSs is important for the development of RA treatment. Tomatidine (Td), a steroidal alkaloid derived from the solanaceae family, has been reported to have anti-inflammatory, anti-tumor and immunomodulatory effects. However, its effect on RA remains unknown. Here, we examined the inhibitory effect of Td on TNFα-induced arthritic FLSs, and subsequently investigated its therapeutic effect on collagen-induced arthritis (CIA) rats. Our results revealed that Td significantly inhibited TNFα-induced proliferation and migration of arthritic FLSs. In addition, we found that Td treatment could efficaciously ameliorate synovial inflammation and joint destruction of rats with CIA. Both in vitro and in vivo studies showed that Td significantly suppressed the production of pro-inflammatory cytokines including IL-1ß, IL-6 and TNFα, and downregulated the expression of MMP-9 and RANKL. Further molecular mechanism studies revealed that the inhibitory effect of Td on RA might attribute to the decreased activations of MAPKs (ERK and JNK) and NF-κB. These findings provide evidence that Td has the potential to be developed into a complementary or alternative agent for RA therapy.

Difference in light use strategy in red alga between Griffithsia pacifica and Porphyridium purpureum.

Phycobilisomes (PBSs) are the largest light-harvesting antenna in red algae, and feature high efficiency and rate of energy transfer even in a dim environment. To understand the influence of light on the energy transfer in PBSs, two red algae Griffithsia pacifica and Porphyridium purpureum living in different light environment were selected for this research. The energy transfer dynamics in PBSs of the two red algae were studied in time-resolved fluorescence spectroscopy in sub-picosecond resolution. The energy transfer pathways and the related transfer rates were uncovered by deconvolution of the fluorescence decay curve. Four time-components, i.e., 8 ps, 94 ps, 970 ps, and 2288 ps were recognized in the energy transfer in PBSs of G. pacifica, and 10 ps, 74 ps, 817 ps and 1292 ps in P. purpureum. In addition, comparison in energy transfer dynamics between the two red algae revealed that the energy transfer was clearly affected by lighting environment. The findings help us to understand the energy transfer mechanisms of red algae for adaptation to a natural low light environment.

Plasmon-induced double-field-enhanced upconversion nanoprobes with near-infrared resonances for high-sensitivity optical bio-imaging.

High-sensitivity optical imaging can be achieved through improving upconversion photoluminescence (UCPL) efficiency of localized surface plasmon resonance (LSPR)-enhanced excitation and emission. Herein, we report a type of UCPL nanoprobe, Au nanospheres assemblage@Gd2O3:Yb3+/Ln3+(Ln = Er, Ho, Tm), which exhibits emission enhancements from 46- to 96-fold as compared with its Au-free counterparts. The aggregation and interaction among Au nanospheres embedded inside the nanoprobe brings about three characteristic LSPR peaks in visible and near-infrared regions according to simulated and experimental absorption spectra, resulting in both excitation and emission fields simultaneously intensified all through the entire nanoprobe. We addressed a characteristic wavelength dependence on emission amplifications, which could be elucidated by a LSPR-enhanced UCPL mechanism and relevant rate equations that we addressed. The nanoprobe was verified to have a superior capability for optical bio-imaging with a negligible toxicityin vitroandin vivo. This study realizes a synchronous double-field-enhanced upconversion of optical nanoprobein situ, and may gain an insight into its mechanism underlying for LSPR-induced UCPL enhancement.

Clinical features and mortality-related factors of extensive burns among young adults: the Kunshan disaster experience.

BACKGROUND: The aim of the study was to identify the clinical features and the factors associated with burn induced mortality among young adults after exposure to indoor explosion and fire. METHODS: This is an observational study which included burn patients who were admitted to eighteen ICUs after a fire disaster. Epidemiologic and clinical characteristics, as well as therapy were recorded. The primary outcome was 90-day mortality. The mortality-related factors were also analyzed. RESULTS: There were 167 burn patients enrolled in the study, the median age was 38 years, 62 (37.1%) patients died within 90 days. Seventy-one percent of patients had a burn size ≥90% TBSA, and 73.7% of patients had a full-thickness burn area above 50% TBSA. The survivors had lower Baux scores, and received earlier escharectomy and autologous skin grafts. The 50% mortality rates (LA50s) for burn size and full-thickness burn area were 95.8% and 88.6% TBSA, respectively. The multivariate analysis showed that full-thickness burn area over 50% TBSA and residual burned surface area (RBSA)/TBSA at 28 days were strong predictors of mortality among burn patients (odds ratio 2.55; 95% CI, 1.01 to 6.44, P=0.047; odds ratio 1.07; 95% CI, 1.04 to 1.09, P<0.001). The ROC curve-based cut-off values of RBSA/TBSA at 28 days for predicting 90-day mortality were 62.5%. CONCLUSIONS: Burn size and full-thickness burn area were the main risk factors for poor outcome in patients with extensive burns. Earlier escharectomy and autologous skin grafts may improve outcomes.

Hedgehog signaling activation required for glypican-6-mediated regulation of invasion, migration, and epithelial-mesenchymal transition of gastric cancer cells.

Gastric cancer (GC) is the fifth most common cancer worldwide and one of the most aggressive cancers in China. Glypican 6 is highly expressed in gastric adenocarcinoma and may act as a diagnostic and prognostic marker; however, the functional importance and molecular mechanism of glypican 6 in GC remains unclear. In the current study, we aimed to reveal the function and mechanism of glypican 6 in two GC cell lines: MKN-45 and SGC-7901. We found higher expression of glypican 6 in MKN-45 and SGC-7901 cells than in cells from the normal gastric mucosa epithelial cell line GES-1. Glypican 6 knockdown suppressed MKN-45 and SGC-7901 cell proliferation. A Transwell assay confirmed that glypican 6 silencing inhibited the migration and invasiveness of MKN-45 and SGC-7901 cells. Epithelial-to-mesenchymal transition (EMT) markers were determined by western blotting, and the results showed reduced Vimentin expression and elevated E-cadherin expression in glypican 6 short interfering RNA (siRNA) transfected MKN-45 and SGC-7901 cells. However, glypican 6 overexpression in GES-1 cells showed no significant promotion on GES-1 cells proliferation and migration. Further studies confirmed that glypican 6 siRNA regulated Hedgehog and Gli1 signaling and participated in the function of glypican 6 on MKN-45 and SGC-7901 cell migration and invasion. Our findings suggest that decreased glypican 6 expression inhibits the migration and invasion ability of GC cells.

Resibufogenin suppresses tumor growth and Warburg effect through regulating miR-143-3p/HK2 axis in breast cancer.

Increasing evidence confirmed that the Warburg effect plays an important role involved in the progression of malignant tumors. Resibufogenin (RES) has been proved to have a therapeutic effect in multiple malignant tumors. However, the mechanism of whether RES exerted an antitumor effect on breast cancer through regulating the Warburg effect is largely unknown. The effect of RES on glycolysis was determined by glucose consumption, lactate production, ATP generation, extracellular acidification rate and oxygen consumption rate in breast cancer cells. The total RNA and protein levels were respectively measured by RT-qPCR and western blot. Cell proliferation and apoptosis were examined using the CCK-8 assay, colony formation assay, and flow cytometry, respectively. The interaction between miR-143-3p and HK2 was verified by dual-luciferase reporter gene assay. We also evaluated the influence of RES on the tumor growth and Warburg effect in vivo. RES treatment significantly decreased glycolysis, cell proliferation and induced apoptosis of both MDA-MB-453 and MCF-7 cells. Simultaneously, the expression of HK2 was decreased in breast cancer cells treated with RES, which was positively associated with tumor size and glycolysis. Moreover, HK2 was a direct target gene of miR-143-3p. Mechanistically, upregulation of miR-143-3p by RES treatment inhibited tumor growth by downregulating HK2-mediated Warburg effect in breast cancer. Our findings suggested that RES exerted anti-tumorigenesis and anti-glycolysis activities in breast cancer through upregulating the inhibitory effect of miR-143-3p on HK2 expression, which provided a new potential strategy for breast cancer clinical treatment.

Phillyrin Attenuates Osteoclast Formation and Function and Prevents LPS-Induced Osteolysis in Mice.

As the sole cell type responsible for bone resorption, osteoclasts play a pivotal role in a variety of lytic bone diseases. Suppression of osteoclast formation and activation has been proposed as an effective protective therapy for new bone. In this study, we reported for the first time that phillyrin (Phil), an active ingredient extracted from forsythia, significantly inhibited RANKL-induced osteoclastogenesis and bone resorption in vitro and protected against lipopolysaccharide-induced osteolysis in vivo. Further molecular investigations demonstrated that Phil effectively blocked RANKL-induced activations of c-Jun N-terminal kinase and extracellular signal-regulated kinase, which suppressed the expression of c-Fos and nuclear factor of activated T-cells cytoplasmic 1. Taken together, these data suggested that Phil might be a potential antiosteoclastogenesis agent for treating osteoclast-related bone lytic diseases.

Self-assembly and self-delivery nanodrug of bortezomib: a simple approach to achieve the trade-off between functionality and druggability.

Bortezomib, dietary tannic acid and an FDA-approved excipient poloxamer were used as building blocks without any chemical syntheses and modifications to construct a dynamic self-delivery nanodrug with high drug loading, outstanding stability, tunable size and pH-controlled release. This strategy with high druggability, reproducibility and productivity might be desirable and useful for pharmaceutical formulations of bortezomib.

Giant two- to five-photon absorption in CsPbBr2.7I0.3 two-dimensional nanoplatelets.

CsPbBr2.7I0.3 two-dimensional (2D) nanoplatelets (NPs) with emission wavelengths of 469 nm and 527 nm were synthesized and characterized. Femtosecond transient absorption spectra revealed hot carrier cooling times of ∼368 fs and ∼438 fs for 469 nm and 527 nm 2D NPs, respectively. Importantly, the 2D NPs exhibit giant two-, three-, four-, and five-photon absorption cross-sections, reaching ∼4.1×106 GM at 830 nm, ∼2.3×10-74 cm6 s2 photon-2 at 1300 nm, 2.06×10-104 cm8 s3 photon-3 at 1600 nm, and 1.50×10-136 cm10 s4 photon-4 at 2200 nm, respectively, which are 3-8 orders of magnitude larger, compared to specially designed organic molecules.

Direct Observation of Corner States in Second-Order Topological Photonic Crystal Slabs.

Recently, higher-order topological phases that do not obey the usual bulk-edge correspondence principle have been introduced in electronic insulators and brought into classical systems, featuring in-gap corner or hinge states. In this Letter, using near-field scanning measurements, we show the direct observation of corner states in second-order topological photonic crystal slabs consisting of periodic dielectric rods on a perfect electric conductor. Based on the generalized two-dimensional Su-Schrieffer-Heeger model, we show that the emergence of corner states roots in the nonzero edge dipolar polarization instead of the nonzero bulk quadrupole polarization. We demonstrate the topological transition of two-dimensional Zak phases of photonic crystal slabs by tuning intracell distances between two neighboring rods. We also directly observe in-gap one-dimensional edge states and zero-dimensional corner states in the microwave regime. Our work presents that the photonic crystal slab is a powerful platform to directly observe topological states and paves the way to study higher-order photonic topological insulators.

An injectable and tumor-specific responsive hydrogel with tissue-adhesive and nanomedicine-releasing abilities for precise locoregional chemotherapy.

Locoregional chemotherapy, especially using implantable hydrogel depots to sustainably deliver chemotherapeutics at tumor site, has shown great potential for improving antitumor efficacy and reducing systemic toxicity. However, the hydrogel applications are limited by some intrinsic constraints, especially the contradiction between increasing drug penetration and accumulation in tumor and decreasing random drug diffusion into surrounding normal tissues. Herein, we report a unique "Jekyll and Hyde" nanoparticle-hydrogel (NP-gel) hybrid platform, which can keep dormant in adjacent normal tissues but be activated by mildly acidic and hyaluronidase-rich microenvironment in malignant tumor tissues to unidirectionally release tumor-targeting and penetrative doxorubicin (DOX)-loaded NPs. Apart from tumor-specific recognition, penetration, internalization and release, NP-gel features: shear-thinning behavior for injection, tissue-adhesiveness for continuous on-site activation, and full biodegradability for safe use. Precise delivery was clearly demonstrated in both tumor-grafted and tumor-resected mice. A single peritumoral injection of DOX-loaded NP-gel exhibited a significantly higher drug accumulation in tumor for 3 weeks than in nontarget organs and thus long-term tumor remission. More importantly, significant inhibition in tumor recurrence without detectable toxicity to healthy organs was demonstrated when applied after tumor resection. The designed system displayed long-acting and precise anticancer efficacy, paving the way toward effective tumor locoregional treatment. STATEMENT OF SIGNIFICANCE: Injectable hydrogels, allowing sustained drug delivery directly at tumor site, has shown great potential for locoregional chemotherapy. However, how to achieve tumor-specific drug accumulation but meanwhile impede the random drug diffusion into surrounding normal tissues remains an insurmountable challenge, especially considering high drug concentration gradient, higher interstitial fluid pressure and denser extracellular matrix in tumor than adjacent normal tissue. Herein, a 'Jekyll and Hyde' nanoparticle-hydrogel hybrid formulation was designed to keep dormant in adjacent normal tissues but be activated by mildly acidic and hyaluronidase-rich microenvironment in malignant tumor tissues to unidirectionally release tumor-targeting and penetrative DOX-loaded nanoparticles, leading to a significant tumor inhibition and antirecurrence efficiency without detectable toxicity to healthy organs, thus presenting great potential for precise locoregional chemotherapy.

A prospective observation on nutrition support in adult patients with severe burns.

Nutrition therapy is considered an important treatment of burn patients. The aim of the study was to delineate the nutritional support in severe burn patients and to investigate association between nutritional practice and clinical outcomes. Severe burn patients were enrolled (n 100). In 90 % of the cases, the burn injury covered above 70 % of the total body surface area. Mean interval from injury to nutrition start was 2·4 (sd 1·1) d. Sixty-seven patients were initiated with enteral nutrition (EN) with a median time of 1 d from injury to first feed. Twenty-two patients began with parenteral nutrition (PN). During the study, thirty-two patients developed EN intolerance. Patients received an average of about 70 % of prescribed energy and protein. Patients with EN providing <30 % energy had significantly higher 28- d and in-hospital mortality than patients with EN providing more than 30 % of energy. Mortality at 28 d was 11 % and in-hospital mortality was 45 %. Multiple regression analysis demonstrated that EN providing <30 % energy and septic shock were independent risk factors for 28- d prognosis. EN could be initiated early in severe burn patients. Majority patients needed PN supplementation for energy requirement and EN feeding intolerance. Post-pyloric feeding is more efficient than gastric feeding in EN tolerance and energy supplement. It is difficult for severe burn patients to obtain enough feeding, especially in the early stage of the disease. More than 2 weeks of underfeeding is harmful to recovery.

A silicon-on-insulator slab for topological valley transport.

Backscattering suppression in silicon-on-insulator (SOI) is one of the central issues to reduce energy loss and signal distortion, enabling for capability improvement of modern information processing systems. Valley physics provides an intriguing way for robust information transfer and unidirectional coupling in topological nanophotonics. Here we realize topological transport in a SOI valley photonic crystal slab. Localized Berry curvature near zone corners guarantees the existence of valley-dependent edge states below light cone, maintaining in-plane robustness and light confinement simultaneously. Topologically robust transport at telecommunication is observed along two sharp-bend interfaces in subwavelength scale, showing flat-top high transmission of ~10% bandwidth. Topological photonic routing is achieved in a bearded-stack interface, due to unidirectional excitation of valley-chirality-locked edge state from the phase vortex of a nanoscale microdisk. These findings show the prototype of robustly integrated devices, and open a new door towards the observation of non-trivial states even in non-Hermitian systems.

Liposomes-Camouflaged Redox-Responsive Nanogels to Resolve the Dilemma between Extracellular Stability and Intracellular Drug Release.

Liposomes have shown great promises for pharmaceutical applications, but still suffer from the poor storage stability, undesirable drug leakage, and uncontrolled drug release. Herein, liposomes-camouflaged redox-responsive nanogels platform (denoted as "R-lipogels") is prepared to integrate the desirable features of sensitive nanogels into liposomes to circumvent their intrinsic issues. The results indicate that drug-loaded R-lipogels with controlled size and high stability not only can achieve a very high doxorubicin (DOX)-loading capacity (12.9%) and encapsulation efficiency (97.3%) by ammonium sulfate gradient method and very low premature leakage at physiological condition, but also can quickly release DOX in the reducing microenvironment of tumor cells, resulting in effective growth inhibition of tumor cells. In summary, the strategy given here provides a facile approach to develop liposomes-nanogels hybrid system with combined beneficial features of stealthy liposomes and responsive nanogels, which potentially resolves the dilemma between systemic stability and intracellular rapid drug release.