Direct generation of a 635 nm red random laser based on praseodymium (Pr)-doped ZBLAN fiber.

Visible random fiber lasers have garnered significant attention due to their unique emission properties and potential applications in various fields. We first, to the best of our knowledge, demonstrated a compact all-fiber structure, red wavelength, and random fiber laser (RFL) based on a double-clad Pr-doped ZBLAN fiber. The simple half-open cavity consists of a high-reflectivity fiber pigtail mirror and the Pr-doped ZBLAN fiber. The Pr-doped ZBLAN fiber not only served as a gain medium but also offered random backward scattering. We investigated the effects of different lengths on output power and slope efficiency of the RFL. For 21 m Pr-doped fiber, the RFL emitted a maximum output power of 208.50 mW with a slope efficiency of 11.09%. For 15 m Pr-doped fiber, the maximum power decreased to 120.18 mW with the slope efficiency of 7.27%. We are also numerically simulating the output power versus the pump power at different fiber lengths based on power steady-state light propagation equations. This novel RFL has the potential for broad applications in fields such as display technology, spectroscopy, biomedical imaging, and optical sensing due to its unique properties and simple all-fiber structure.

DDIT3/CHOP promotes LPS/ATP-induced pyroptosis in osteoblasts via mitophagy inhibition.

Inflammatory environments can trigger endoplasmic reticulum (ER) stress and lead to pyroptosis in various tissues and cells, including liver, brain, and immune cells. As a key factor of ER stress, DNA damage-inducible transcript 3 (DDIT3)/CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) is upregulated in osteoblasts during inflammatory stimulation. DDIT3/CHOP may therefore regulate osteoblast pyroptosis in inflammatory conditions. During this investigation, we found that lipopolysaccharides (LPS)/adenosine 5'-triphosphate (ATP) stimulation in vitro induced osteoblasts to undergo pyroptosis, and the expression of DDIT3/CHOP was increased during this process. The overexpression of DDIT3/CHOP further promoted osteoblast pyroptosis as evidenced by the increased expression of the inflammasome NLR family pyrin domain containing 3 (NLRP3) and ratios of caspase-1 p20/caspase-1 and cleaved gasdermin D (GSDMD)/GSDMD. To explore the specific mechanism of this effect, we found through fluorescence imaging and Western blot analysis that LPS/ATP stimulation promoted PTEN-induced kinase 1 (PINK1)/E3 ubiquitin-protein ligase parkin (Parkin)-mediated mitophagy in osteoblasts, and this alteration was suppressed by the DDIT3/CHOP overexpression, resulting in increased ratio of pyroptosis compared with the control groups. The impact of DDIT3/CHOP on pyroptosis in osteoblasts was reversed by the application of carbonyl cyanide 3-chlorophenylhydrazone (CCCP), a specific mitophagy agonist. Therefore, our data demonstrated that DDIT3/CHOP promotes osteoblast pyroptosis by inhibiting PINK1/Parkin-mediated mitophagy in an inflammatory environment.

DDIT3 deficiency accelerates bone remodeling during bone healing by enhancing osteoblast and osteoclast differentiation through ULK1-mediated autophagy.

The coordination of osteoblasts and osteoclasts is essential for bone remodeling. DNA damage inducible script 3 (DDIT3) is an important regulator of bone and participates in cell differentiation, proliferation, autophagy, and apoptosis. However, its role in bone remodeling remains unexplored. Here, we found that Ddit3 knockout (Ddit3-KO) enhanced both bone formation and resorption. The increased new bone formation and woven bone resorption, i.e., enhanced bone remodeling capacity, was found to accelerate bone defect healing in Ddit3-KO mice. In vitro experiments showed that DDIT3 inhibited both osteoblast differentiation and Raw264.7 cell differentiation by regulating autophagy. Cell coculture assay showed that Ddit3-KO decreased the ratio of receptor activator of nuclear factor-κß ligand (RANKL) to osteoprotegerin (OPG) in osteoblasts, and Ddit3-KO osteoblasts inhibited osteoclast differentiation. Meanwhile, DDIT3 knockdown (DDIT3-sh) increased receptor activator of nuclear factor-κß (RANK) expression in Raw264.7 cells, and DDIT3-sh Raw264.7 cells promoted osteoblast differentiation, whereas, DDIT3 overexpression had the opposite effect. Mechanistically, DDIT3 promoted autophagy partly by increasing ULK1 phosphorylation at serine555 (pULK1-S555) and decreasing ULK1 phosphorylation at serine757 (pULK1-S757) in osteoblasts, thereby inhibiting osteoblast differentiation. DDIT3 inhibited autophagy partly by decreasing pULK1-S555 in Raw264.7 cells, thereby suppressing osteoclastic differentiation. Taken together, our data indicate that DDIT3 is one of the elements regulating bone remodeling and bone healing, which may become a potential target in bone defect treatment.

An optimized denoising method for ICESat-2 photon-counting data considering heterogeneous density and weak connectivity.

The Ice, Cloud, and Land Elevation Satellite-2 (ICESat-2) can obtain underwater elevation due to its strong penetration ability. However, the photons recorded by ICESat-2 include a large amount of noise that needs to be removed. Although density-based clustering methods can finish signal photon extraction, heterogeneous density and weak connectivity in photon data distribution impede their denoising performance, especially for sparse signals in deep water and drastic topographic change areas. In this paper, a novel fused denoising method based on the local outlier factor and inverse distance metric is proposed to overcome the above problems. The local outlier factor and inverse distance metric are calculated based on K-nearest neighbors (KNNs), taking into account not only the difference in density but also the directional uniformity of the data distribution. Using six trajectories under various seabed topographies, the proposed method is compared with state-of-the-art ICESat-2 photon denoising algorithms and official ATL03 results. The results indicate that the overall accuracy of the proposed method can surpass 96%, and the proposed method maintains higher recall but also has a lower false positive rate. Compared with the results of other methods, the proposed method can better adopt areas with abrupt topographic changes and deep water. The extracted signal strips are more unbroken and continuous. This study can contribute to pioneering a new perspective for ICESat-2 photon-counting data denoising research that is limited to using only density-based algorithms.

Potential application of a green fiber laser in laser display systems.

This study explores the application of optical fiber lasers in display systems by integrating a P r3+-doped green all-fiber laser into a laser projection display system. As a control group to compare the results, a 520 nm semiconductor green laser diode module was integrated, similar to the experimental group. The color gamut and speckle performances were studied and compared. The results showed that the experimental group performed slightly better in the color gamut volume. The speckle contrast decreased rapidly in the experimental group when power increased. To our knowledge, this is the first study to apply a fiber laser to a laser display system. The results shed light on developing laser display systems with fewer or no speckle reduction elements.

Point-of-Care and Dual-Response Detection of Hydrazine/Hypochlorite-Based on a Smart Hydrogel Sensor and Applications in Information Security and Bioimaging.

A novel dual-response fluorescence probe (XBT-CN) was developed by using a fluorescence priming strategy for quantitative monitoring and visualization of hydrazine (N2H4) and hypochlorite (ClO-). With the addition of N2H4/ClO-, the cleavage reaction of C=C bond initiated by N2H4/ClO- was transformed into corresponding hydrazone and aldehyde derivatives, inducing the probe XBT-CN appeared a fluorescence "off-on" response, which was verified by DFT calculation. HRMS spectra were also conducted to confirm the sensitive mechanism of XBT-CN to N2H4 and ClO-. The probe XBT-CN had an obvious fluorescence response to N2H4 and ClO-, which caused a significant color change in unprotected eyes. In addition, the detection limits of XBT-CN for N2H4 and ClO- were 27 nM and 34 nM, respectively. Interference tests showed that other competitive analytes could hardly interfere with the detection of N2H4 and ClO- in a complex environment. In order to realize the point-of-care detection of N2H4 and ClO-, an XBT-CN@hydrogel test kit combined with a portable smartphone was developed. Furthermore, the portable test kit has been applied to the detection of N2H4 and ClO- in a real-world environment and food samples, and a series of good results have been achieved. Attractively, we demonstrated that XBT-CN@hydrogel was successfully applied as an encryption ink in the field of information security. Finally, the probe can also be used to monitor and distinguish N2H4 and ClO- in living cells, exhibiting excellent biocompatibility and low cytotoxicity.

Satellite-derived bathymetry integrating spatial and spectral information of multispectral images.

As a significant and cost-effective method of obtaining shallow seabed topography, satellite derived bathymetry (SDB) can acquire a wide range of shallow sea depth by integrating a small quantity of in-situ water depth data. This method is a beneficial addition to traditional bathymetric topography. The seafloor's spatial heterogeneity leads to inaccuracies in bathymetric inversion, which reduces bathymetric accuracy. By utilizing multispectral data with multidimensional features, an SDB approach incorporating spectral and spatial information of multispectral images is proposed in this study. In order to effectively increase the accuracy of bathymetry inversion throughout the entire area, first the random forest with spatial coordinates is established to control bathymetry spatial variation on a large scale. Next, the Kriging algorithm is used to interpolate bathymetry residuals, and the interpolation results are used to adjust bathymetry spatial variation on a small scale. The data from three shallow water sites are experimentally processed to validate the method. Compared with other established bathymetric inversion techniques, the experimental results show that the method effectively reduces the error in bathymetry estimation caused by spatial heterogeneity of the seabed, producing high-precision inversion bathymetry with a root mean square error of 0.78 to 1.36 meters.

Tumor stromal topography promotes chemoresistance in migrating breast cancer cell clusters.

Multicellular clustering provides cancer cells with survival advantages and facilitates metastasis. At the tumor migration front, cancer cell clusters are surrounded by an aligned stromal topography. It remains unknown whether aligned stromal topography regulates the resistance of migrating cancer cell clusters to therapeutics. Using a hybrid nanopatterned model to characterize breast cancer cell clusters at the migration front with aligned stromal topography, we demonstrate that topography-induced migrating cancer cell clusters exhibit upregulated cytochrome P450 family 1 (CYP1) drug metabolism and downregulated glycolysis gene signatures, which correlates with unfavorable prognosis. Screening on approved oncology drugs shows that cancer cell clusters on aligned stromal topography are more resistant to diverse chemotherapeutics. Full-dose drug testings further indicate that topography induces drug resistance of hormone receptor-positive breast cancer cell clusters to doxorubicin and tamoxifen and triple-negative breast cancer cell clusters to doxorubicin by activating the aryl hydrocarbon receptor (AhR)/CYP1 pathways. Inhibiting the AhR/CYP1 pathway restores reactive oxygen species-mediated drug sensitivity to migrating cancer cell clusters, suggesting a plausible therapeutic direction for preventing metastatic recurrence.

A perspective on SARS-CoV-2 virus-like particles vaccines.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) first appeared in Wuhan, China, in December 2019. The 2019 coronavirus disease (COVID-19) pandemic, caused by SARS-CoV-2, has spread to almost all corners of the world at an alarming rate. Vaccination is important for the prevention and control of the COVID-19 pandemic. Efforts are underway worldwide to develop an effective vaccine against COVID-19 using both traditional and innovative vaccine strategies. Compared to other vaccine platforms, SARS-CoV-2 virus-like particles （VLPs ）vaccines, as a new vaccine platform, have unique advantages: they have artificial nanostructures similar to natural SARS-CoV-2, which can stimulate good cellular and humoral immune responses in the organism; they have no viral nucleic acids, have good safety and thermal stability, and can be mass-produced and stored; their surfaces can be processed and modified, such as the adjuvant addition, etc.; they can be considered as an ideal platform for COVID-19 vaccine development. This review aims to shed light on the current knowledge and progress of VLPs vaccines against COVID-19, especially those undergoing clinical trials.

1.3/1.4 µm dual-wave band dissipative soliton resonance in a passively mode-locked Bi-doped phosphosilicate fiber laser.

We report the 1.3/1.4 µm dual-wave band dissipative soliton resonance (DSR) in a passively mode-locked bismuth-doped phosphosilicate fiber (Bi-PSF) laser. The low-water-peak Bi-PSF with two bismuth active centers associated with silicon and phosphorus supports the O+E-band gain. Using a 1239 nm home-made Raman fiber laser as pump source and nonlinear amplifying loop mirror for initiating mode-locking, stable DSR operation at 1343 and 1406 nm is achieved with the spectral bandwidth of 12 and 16 nm. The pulse duration with the pump power increases from 62 to 270 ps with a repetition frequency of 4.069 MHz. The average power is 11.05 mW corresponding to the maximum energy of 2.7 nJ. This is, to the best of our knowledge, the first demonstration of a mode-locked fiber laser in the ∼1.38 µm water absorption band and the O+E dual-wave band operation for applications in all-spectral-band communications, bio-medical imaging, and terahertz difference frequency generation.

Changes of Mutations and Copy-Number and Enhanced Cell Migration during Breast Tumorigenesis.

Although cancer stem cells (CSCs) play a major role in tumorigenesis and metastasis, the role of genetic alterations in invasiveness of CSCs is still unclear. Tumor microenvironment signals, such as extracellular matrix (ECM) composition, significantly influence cell behaviors. Unfortunately, these signals are often lost in in vitro cell culture. This study determines putative CSC populations, examines genetic changes during tumorigenesis of human breast epithelial stem cells, and investigates single-cell migration properties on ECM-mimetic platforms. Whole exome sequencing data indicate that tumorigenic cells have a higher somatic mutation burden than non-tumorigenic cells, and that mutations exclusive to tumorigenic cells exhibit higher predictive deleterious scores. Tumorigenic cells exhibit distinct somatic copy number variations (CNVs) including gain of duplications in chromosomes 5 and 8. ECM-mimetic topography selectively enhances migration speed of tumorigenic cells, but not of non-tumorigenic cells, and results in a wide distribution of tumorigenic single-cell migration speeds, suggesting heterogeneity in cellular sensing of contact guidance cues. This study identifies mutations and CNVs acquired during breast tumorigenesis, which can be associated with enhanced migration of breast tumorigenic cells, and demonstrates that a nanotopographically-defined platform can be applied to recapitulate an ECM structure for investigating cellular migration in the simulated tumor microenvironment.

High-power cylindrical vector beam fiber laser based on an all-polarization-maintaining structure.

We propose and demonstrate an all-polarization-maintaining (PM) high-power cylindrical vector beam (CVB) fiber laser based on the principle of mode superposition. The non-degenerated LPy 11a is generated from the oscillator with the maximum power of 11.9W, whose slope efficiency is 24.4%. Then the stable single TE01 vector beam is achieved by the superposition of LPy 11a and LPx 11b in an all-PM architecture, its output power is 3.1W and mode purity of 91.2%. Due to the all-PM architecture, our configuration is free of adjusting polarization controller (PC) and reliable during long-term operation. This laser could be used as a high-power CVBs source for a wide range of applications towards scientific research and industrial field.

On-chip mid-IR octave-tunable Raman soliton laser.

Photonic chip-based continuously tunable lasers are widely recognized as an indispensable component for photonic integrated circuits (PICs). Specifically, mid-infrared (mid-IR) laser sources are of paramount importance in applications such as photonic sensing and spectroscopy. In this article, we theoretically investigate the propagation dynamics of mid-IR Raman soliton in Ge28Sb12Se60 chalcogenide glass waveguide. By carefully engineer the waveguide dispersion and nonlinear interaction, we propose a suspended chalcogenide glass waveguide device that allows an octave-tuning, from 1.96 µm to 3.98 µm, Raman soliton source. The threshold pump energy is in the low pico-Joule range. Our result provides a solution to continuously tunable on-chip mid-IR ultrafast laser sources.

ICESat-2 laser data denoising algorithm based on a back propagation neural network.

The Ice, Cloud, and Land Elevation Satellite-2 (ICESat-2) photon data is the emerging satellite-based LiDAR data, widely used in surveying and mapping due to its small photometric spot and high density. Since ICESat-2 data collect weak signals, it is difficult to denoise in shallow sea island areas, and the quality of the denoising method will directly affect the precision of bathymetry. This paper proposes a back propagation (BP) neural network-based denoising algorithm for the data characteristics of shallow island reef areas. First, a horizontal elliptical search area is constructed for the photons in the dataset. Suitable feature values are selected in the search area to train the BP neural network. Finally, data with a geographic location far apart, including daily and nightly data, are selected respectively for experiments to test the generality of the network. By comparing the results with the confidence labels provided in the official documents of the ATL03 dataset, the DBSCAN algorithm, and the manual visual interpretation, it is proved that the denoising algorithm proposed in this paper has a better processing effect in shallow island areas.

Optical Enhancement of Diffraction Efficiency of Texas Instruments Phase Light Modulator for Beam Steering in Near Infrared.

Phase light modulator (PLM) by MEMS mirror array operating in a piston-mode motion enables a high-speed diffractive beam steering in a random-access and flexible manner that makes a lidar system more intelligent and adaptive. Diffraction efficiency is determined by the range of the piston motion of the MEMS array; consequently, a larger range of the piston motion is required for beam steering in infrared, such as for lidar. We demonstrated how the range of the piston motion is optically enhanced by a factor of two with a light-recycling optics based on Talbot self-imaging. The proposed optical architecture extends the usable range of the wavelength so that a MEMS-PLM designed for visible wavelength is applicable for a high-efficiency beam steering at an infrared wavelength of 1550 nm with an improved diffraction efficiency of 30%.

An FGFR1-Binding Peptide Modified Liposome for siRNA Delivery in Lung Cancer.

Liposome modification by targeting ligands has been used to mediate specific interactions and drug delivery to target cells. In this study, a new peptide ligand, CP7, was found to be able to effectively bind to FGFR1 through reverse molecular docking and could cooperate with VEGFR3 to achieve targeting of A549 cells. CP7 was modified on the surface of the liposome to construct a targeted and safe nanovehicle for the delivery of a therapeutic gene, Mcl-1 siRNA. Due to the specific binding between CP7 and A549 cells, siRNA-loaded liposome-PEG-CP7 showed increased cellular uptake in vitro, resulting in significant apoptosis of tumor cells through silencing of the Mcl-1 gene, which is associated with apoptosis and angiogenesis. This gene delivery system also showed significantly better antitumor activity in tumor-bearing mice in vivo. All of these suggested that siRNA-loaded liposome-PEG-CP7 could be a promising gene drug delivery system with good bioavailability and minimal side effects for treatment.

Phenylboronic ester-modified polymeric nanoparticles for promoting TRP2 peptide antigen delivery in cancer immunotherapy.

The tremendous development of peptide-based cancer vaccine has attracted incremental interest as a powerful approach in cancer management, prevention and treatment. As successful as tumor vaccine has been, major challenges associated with achieving efficient immune response against cancer are (1) drainage to and retention in lymph nodes; (2) uptake by dendritic cells (DCs); (3) activation of DCs. In order to overcome these barriers, here we construct PBE-modified TRP2 nanovaccine, which comprises TRP2 peptide tumor antigen and diblock copolymer PEG-b-PAsp grafted with phenylboronic ester (PBE). We confirmed that this TRP2 nanovaccine can be effectively trapped into lymph node, uptake by dendritic cells and induce DC maturation, relying on increased negative charge, ROS response and pH response. Consistently, this vehicle loaded with TRP2 peptide could boost the strongest T cell immune response against melanoma in vivo and potentiate antitumor efficacy both in tumor prevention and tumor treatment without any exogenous adjuvant. Furthermore, the TRP2 nanovaccine can suppress the tumor growth and prolong animal survival time, which may result from its synergistic effect of inhibiting tumor immunosuppression and increasing cytotoxic lymphocyte (CTL) response. Hence this type of PBE-modified nanovaccine would be widely used as a simple, safe and robust platform to deliver other antigen in cancer immunotherapy.

[Differences in the ecological resilience of planted and natural Pinus massoniana and Cunninghamia lanceolata forests in response to drought in subtropical China]. / 亚热带人工和天然马尾松、杉木林生长对干旱的生态弹性差异.

We sampled Pinus massoniana and Cunninghamia lanceolata in both plantation and natural forests in central and western Fujian Province, China. Using tree-ring width, tree-ring width index, and basal area increment, we reconstructed the annual growth of 109 conifer individuals from four sites for the 20-year period from 1993 to 2012. We then calculated resistance, recovery, and resilience indices of those trees in response to two consecutive extreme droughts (2003-2004 and 2011) and analyzed the differences in resistance and resilience between plantations and natural fore-sts. The results showed that there were temporal differences in moisture requirements between P. massoniana and C. lanceolata, which accounted for their inconsistent responses to drought in 2003-2004. For both species, drought induced a marked growth reduction, without any clear lag effect. The growth responses during and following the 2003-2004 drought were significantly stronger than that for the 2011 drought. Those results indicated that P. massoniana was more resilient to drought stress than C. lanceolata, and the natural forests were more sensitive than plantations, but with stronger capacity to recover. C. lanceolata plantations were more susceptible to frequent extreme drought events. To mitigate the vulnerability of plantation trees to more frequent droughts in the future, we suggested select trees from genetic provenances with strong drought resistance.

[Ecological resilience of ancient Pinus massoniana trees to climate change and insect infestation in southeastern Fujian, China]. / é—½ä¸œå—åœ°åŒºé©¬å°¾æ¾å¤æ ‘å¯¹æ°”å€™å˜åŒ–å’Œè™«ç¾çš„ç”Ÿæ€å¼¹æ€§.

Pinus massoniana is a typical pioneer afforestation tree species widely distributed in southern China. It is crucial to study the ecological resilience of P. massoniana to disturbances under global warming, drying, and frequent pest infestation, which can shed lights on forest mana-gements. In this study, tree-ring samples collected from old-growth P. massoniana trees in Baisong Village, Xianyou County, Fujian Province, were used to develop the first standard chronology of P. massoniana ring width (1865-2014) in this region. The results showed that the low relative humidity from July to September and the extremely high temperature from May to September were the main limiting factors for tree growth. The extremely narrow years were identified in 1869, 1889, 1986, 1991 and 1993. These extremely narrow years were exacerbated after the persistently low values of the previously two years via the superposed epoch analysis (SEA). The insect infestations were more likely to happen in dry years. Insect outbreak exerted strongest effect on tree growth in 1889. The narrow tree-rings in 1986 and 1991 were affected by both insect infestation and drought. The other extremely narrow years were mainly affected by drought. The resistance of trees to insect infestation was weaker than that to drought event. The relative resilience of trees to insect infestation was higher than that to drought event, except for 1991. The relative resilience was the highest in 1889 and the lowest in 1991 under the influence of successive extreme events. Under the enhanced drying trend since 2000, more trees had died possibly due to the combined effects of insect infestation and drought.

An Integrated Tumor Microenvironment Responsive Polymeric Micelle for Smart Drug Delivery and Effective Drug Release.

Tumor microenvironment (TME) responsive polymeric micelles are promising carriers for drug delivery. In order to meet the needs of various applications, multifarious TME-responsive switches are used to construct smart polymeric micelles, which causes the complexity and corpulence of the polymeric micelle system and increases the difficulty of preparation. In this study, we designed and synthesized an ingenious TME-responsive switch through grafting disulfide bond-modified piperidinepropionic acid (CPA) on copolymer poly(ethylene glycol)-b-poly(aspartate)(PEG-b-PAsp) and built a novel pH/reduction-responsive PEG-b-PAsp-g-CPA polymeric micelle delivery system. The CPA-pendants can reverse the surface charge of the polymeric micelle from negative to positive at pH 6.5 because of the protonation of piperidine groups, thereby enhancing the internalization of cell. Subsequently, more piperidine groups are protonated at pH 5.0 which will increase the hydrophilicity of polymeric micelles and cause the hydrophobic core to swell, thus making the disulfide bonds packed in the core to be more easily broken by GSH. With the synergistic effect of the pH-triggered protonation of piperidine groups and reduction triggered break of disulfide bonds, the polymeric micelles will disintegrate and achieve efficient intracellular drug release. The TME-responsive polymeric micelles exhibited good biological safety, enhanced internalization, and rapid intracellular doxorubicin (DOX) release in vitro. Moreover, the PEG-b-PAsp-g-CPA/DOX polymeric micelles showed excellent antitumor efficacy and low systemic toxicity in lung tumor-bearing BALB/C mice. These results indicated that the novel integrated TME-responsive switch CPA helps the PEG-b-PAsp-g-CPA polymeric micelles to obtain excellent TME-responsiveness and antitumor drug delivery capabilities, while it also makes the preparation of TME-responsive polymeric micelles simpler and more convenient. This work provides a new idea for the architecture of TME-responsive polymeric micelles.