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Background: The relation between climate change and human health has become one of the major worldwide public health issues. However, the evidence for low-latitude plateau regions is limited, where the climate is unique and diverse with a complex geography and topography. objectives: This study aimed to evaluate the effect of ambient temperature on the mortality burden of nonaccidental deaths in Yunnan Province and to further explore its spatial heterogeneity among different regions. Methods: We collected mortality and meteorological data from all 129 counties in Yunnan Province from 2014 to 2020, and 16 prefecture-level cities were analyzed as units. A distributed lagged nonlinear model was used to estimate the effect of temperature exposure on years of life lost (YLL) for nonaccidental deaths in each prefecture-level city. The attributable fraction of YLL due to ambient temperature was calculated. A multivariate meta-analysis was used to obtain an overall aggregated estimate of effects, and spatial heterogeneity among 16 prefecture-level cities was evaluated by adjusting the city-specific geographical characteristics, demographic characteristics, economic factors, and health resources factors. Results: The temperature-YLL association was nonlinear and followed slide-shaped curves in all regions. The cumulative cold and heat effect estimates along lag 0-21 days on YLL for nonaccidental deaths were 403.16 (95% empirical confidence interval [eCI] 148.14-615.18) and 247.83 (95% eCI 45.73-418.85), respectively. The attributable fraction for nonaccidental mortality due to daily mean temperature was 7.45% (95% eCI 3.73%-10.38%). Cold temperature was responsible for most of the mortality burden (4.61%, 95% eCI 1.70-7.04), whereas the burden due to heat was 2.84% (95% eCI 0.58-4.83). The vulnerable subpopulations include male individuals, people aged <75 years, people with education below junior college level, farmers, nonmarried individuals, and ethnic minorities. In the cause-specific subgroup analysis, the total attributable fraction (%) for mean temperature was 13.97% (95% eCI 6.70-14.02) for heart disease, 11.12% (95% eCI 2.52-16.82) for respiratory disease, 10.85% (95% eCI 6.70-14.02) for cardiovascular disease, and 10.13% (95% eCI 6.03-13.18) for stroke. The attributable risk of cold effect for cardiovascular disease was higher than that for respiratory disease cause of death (9.71% vs 4.54%). Furthermore, we found 48.2% heterogeneity in the effect of mean temperature on YLL after considering the inherent characteristics of the 16 prefecture-level cities, with urbanization rate accounting for the highest proportion of heterogeneity (15.7%) among urban characteristics. Conclusions: This study suggests that the cold effect dominated the total effect of temperature on mortality burden in Yunnan Province, and its effect was heterogeneous among different regions, which provides a basis for spatial planning and health policy formulation for disease prevention.

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This comprehensive review inspects the therapeutic potential of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) across multiple organ systems. Examining their impact on the integumentary, respiratory, cardiovascular, urinary, and skeletal systems, the study highlights the versatility of MSC-EVs in addressing diverse medical conditions. Key pathways, such as Nrf2/HO-1, consistently emerge as central mediators of their antioxidative and anti-inflammatory effects. From expediting diabetic wound healing to mitigating oxidative stress-induced skin injuries, alleviating acute lung injuries, and even offering solutions for conditions like myocardial infarction and renal ischemia-reperfusion injury, MSC-EVs demonstrate promising therapeutic efficacy. Their adaptability to different administration routes and identifying specific factors opens avenues for innovative regenerative strategies. This review positions MSC-EVs as promising candidates for future clinical applications, providing a comprehensive overview of their potential impact on regenerative medicine.

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Background: Research has indicated that VRK1 is essential for the tumor cell cycle. However, its prognostic and immunotherapeutic predictive significance has not been documented in hepatocellular carcinoma (HCC). Methods: The TCGA, ICGC, and GSE14520 datasets were used to investigate VRK1 expression and its predictive significance of survival outcomes. The qRT-PCR and immunohistochemistry (IHC) were used to confirm the findings. The immunotherapeutic response of VRK1 was anticipated by the IMvigor210 cohort. Lastly, the association between immune infiltration, m6A modification, and functional enrichment of differentially expressed genes (DEGs) was investigated in connection to VRK1 expression. Results: VRK1 expression was markedly elevated on both the mRNA and protein levels in HCC. In HCC patients, a high expression of VRK1 was linked to a poor prognosis. Furthermore, there was a substantial positive correlation seen between increased VRK1 expression and the response rate to anti-PD-L1 immunotherapy. Relationships between VRK1 and m6A-related genes as well as different immune cells were shown by correlation studies. Lastly, enrichment analysis revealed a tight relationship between VRK1 and important biological functions, including DNA replication, cell cycle control, and fatty acid metabolism. Conclusion: Our research reveals the potential of VRK1 as a novel biomarker for prognosis and immunotherapy response in HCC patients.

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With the distinct advantages of high resolution, small pixel size, and multi-level pure phase modulation, liquid crystal on silicon (LCoS) devices afford precise and reconfigurable spatial light modulation that enables versatile applications ranging from micro-displays to optical communications. However, LCoS devices suffer from a long-standing problem of polarization-dependent response in that they only perform phase modulation on one linear polarization of light, and polarization-independent phase modulation-essential for most applications-have had to use complicated polarization-diversity optics. We propose and demonstrate, for the first time, an LCoS device that directly achieves high-performance polarization-independent phase modulation at telecommunication wavelengths with 4K resolution and beyond by embedding a polarization-rotating metasurface between the LCoS backplane and the liquid crystal phase-modulating layer. We verify the device with a number of typical polarization-independent application functions including beam steering, holographical display, and in a key optical switching element - wavelength selective switch (WSS), demonstrating the significant benefits in terms of both configuration simplification and performance improvement.

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BACKGROUND: Small molecular natural products, such as betaine, have unique moisturizing advantages. Capparis spinosa L. fruit is rich in quaternary ammonium alkaloids such as betaine and stachydrine. However, few studies investigated its efficacy and mechanism on human skin. OBJECTIVE: Polysaccharides-free C. spinosa fruit extract (CS) was obtained to study its moisturizing effect and mechanisms focusing on filaggrin (FLG) synthesis and degradation. METHODS: The clinical moisturizing test was carried out on human arms, calves, and faces after CS treatment for 0.5-6 h. The change in the level of FLG, caspase 14, loricrin, and transglutaminase 5 (TGM 5) was measured by immunofluorescence after CS treatment for 4 and 24 h in a reconstructed epidermis model. Also, the content of pyrrolidone carboxylic acid (PCA) in the stratum corneum was tested by high-performance liquid chromatography (HPLC) both in the epidermis model and human calves. RESULTS: Compared with glycerin (positive control), 5% CS showed a strong skin hydration effect on arms and calves when applied for 0.5-6 h. Also, the face hydration increased at 0.5 and 4 h. In addition, 3% CS applied to the recombinant epidermis model under low humidity promoted the immunodetected levels of caspase 14 and PCA content but reduced the levels of FLG at 4 h, however, the levels of FLG, loricrin, and TGM 5 were promoted at 24 h. Meanwhile, CS treatment for 4 h in human calves increased the PCA content in the stratum corneum by 29.9%. CONCLUSIONS: Topical application of CS on human skin showed an instant and long-lasting increase in skin hydration by regulating the FLG network. It promoted FLG degradation to form PCA at 4 h both in vivo and in vitro, increasing FLG synthesis after 24 h, potentially reforming the FLG monomer reservoir to alleviate the skin's dry condition.

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BACKGROUND: Sensitive skin (SS) is a clinical syndrome defined by the occurrence of unpleasant sensations (such as stinging, burning, pain, pruritus, and tingling) in response to stimuli that normally should not provoke them. According to growing evidence, transient receptor potential vanilloid subtype 1 (TRPV1) has elevated expression in individuals with SS and is linked with the severity of SS symptoms. However, its pathogenesis is still unknown. OBJECTIVE: Herein, Citrus reticulata (Tangerine) fruit extract (CR) was obtained and examined for its effect on SS with a focus on TRPV1 stimulation and expression. METHODS: A recombinant hTRPV1 over-expression cell line (HaCaT-TRPV1-OE cell) was constructed to screen substances and extracts from several plants. Intracellular calcium mobilization was monitored by Flexstation 3 and a fluorescence microscope using Fluo 8 AM fluorophore. Next, immunofluorescence was used to detect the TRPV1 expression under different stimulants treated for 24 h. To investigate the relief and increased tolerance of CR to lactic acid-induced skin discomfort, clinical tests were carried out on the nasolabial folds or cheek areas. RESULTS: According to the obtained results, compared to HaCaT cells, HaCaT-TRPV1-OE cells showed a higher expression of TRPV1. Neuronal hyperresponsiveness in SS triggered by capsaicin (CAP), lactic acid, phenoxyethanol or nicotinamide may be through activation of TRPV1 and increased TRPV1 expression. CAP activates TRPV1 in HaCaT-TRPV1-OE cells, and more than 100 plants or chemicals were tested for their inhibitory effects before being screened for CR. CR (1%-4%) inhibited TRPV1 activation induced by CAP or phenoxyethanol or nicotinamide. Meanwhile, CR (0.25%) suppressed TRPV1 protein expression induced by phenoxyethanol or lactic acid. In vivo results showed that CR not only instantly relieved lactic acid-induced skin discomfort under 5 min but also enhanced skin tolerance to lactic acid after 7 days of continuous use. CONCLUSIONS: Topical application of CR showed an instant and long-lasting improvement in SS by modulating the activation and expression of TRPV1. Moreover, it has been suggested that CR might act as a TRPV1 inhibitor to reduce skin irritation or sensitivity.

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Driven by the ever-increasing demand for fingerprint-resistant techniques in modern society, numerous researches have proposed to develop innovative antifingerprint coatings based on superhydrophobic/superoleophobic surface design. However, whether superhydrophobic/superoleophobic surfaces have favorable repellency to the microscopic fingerprint is in fact an open question. Here, we establish a reliable method that enables evaluating the antifingerprint capability of various surfaces in a quantitative way. We show that superhydrophobicity is irrelevant with fingerprint repellency. Regarding superoleophobic surfaces, two distinct wetting states of microscopic fingerprint residues, i.e., the "repellent" and the "collapsed" states, are revealed. Only in the "repellent" state, in which the fingerprint residues remain atop surface textures upon being pressed, superoleophobic surfaces can bring about favorable antifingerprint repellency, which correlates positively with their receding contact angles. A finger-deformation-dependent intrusion mechanism is proposed to account for the formation of different fingerprint wetting states. Our findings offer important insights into the mechanism of fingerprint repellency and will help the design of high-performance antifingerprint surfaces for diverse applications.

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Optical modulators were, are, and will continue to be the underpinning devices for optical transceivers at all levels of the optical networks. Recently, heterogeneously integrated silicon and lithium niobate (Si/LN) optical modulators have demonstrated attractive overall performance in terms of optical loss, drive voltage, and modulation bandwidth. However, due to the moderate Pockels coefficient of lithium niobate, the device length of the Si/LN modulator is still relatively long for low-drive-voltage operation. Here, we report a folded Si/LN Mach-Zehnder modulator consisting of meandering optical waveguides and meandering microwave transmission lines, whose device length is approximately two-fifths of the unfolded counterpart while maintaining the overall performance. The present devices feature a low half-wave voltage of 1.24 V, support data rates up to 128 gigabits per second, and show a device length of less than 9 mm.

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Simple systems in which strong coupling of different excitations can be easily realized are highly important, not only for fundamental research but also for practical applications. Here, we proposed a T-shaped gold nanorod (GNR) dimer composed of a long GNR and a short GNR perpendicular to each other and revealed that the dark quadrupole mode of the long GNR can be activated by utilizing the dipole mode excited in the short GNR. It was found that the strong coupling between the dipole and quadrupole modes can be achieved by exciting the T-shaped GNR dimer with a plane wave. Then, we demonstrated the realization of strong dipole-quadrupole-exciton coupling by placing a T-shaped GNR on a tungsten disulfide (WS2) monolayer, which leads to a Rabi splitting as large as ~299 meV. It was confirmed that the simulation results can be well fitted by using a Hamiltonian based on the coupled harmonic oscillator model and the coupling strengths for dipole-quadrupole, dipole-exciton and quadrupole-exciton can be extracted from the fitting results. Our findings open new horizons for realizing strong plasmon-exciton coupling in simple systems and pave the way for constructing novel plasmonic devices for practical applications.

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In this work, we proposed and experimentally demonstrated a compact and low polarization-dependent silicon waveguide crossing based on subwavelength grating multimode interference couplers. The subwavelength grating structure decreases the effective refractive index difference and shrinks the device footprint. Our designed device is fabricated on the 220-nm SOI platform and performs well. The measured crossing is characterized with low insertion loss (< 1 dB), low polarization-dependence loss (< 0.6 dB), and low crosstalk (< -35 dB) for both TE and TM polarizations with a compact footprint of 12.5 µm × 12.5 µm.

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Integral imaging is a promising three-dimensional (3D) imaging technique that captures and reconstructs light field information. Microlens arrays are usually used for the reconstruction process to display 3D scenes to the viewer. However, the inherent chromatic aberration of the microlens array reduces the viewing quality, and thus, broadband achromatic imaging remains a challenge for integral imaging. Here, we realize a silicon nitride metalens array in the visible region that can be used to reconstruct 3D optical scenes in the achromatic integral imaging for white light. The metalens array contains 60 × 60 polarization-insensitive metalenses with nearly diffraction-limited focusing. The nanoposts in each high-efficiency (measured as 47% on average) metalens are delicately designed with zero effective material dispersion and an effective achromatic refractive index distribution from 430 to 780 nm. In addition, such an achromatic metalens array is composed of only a single silicon nitride layer with an ultrathin thickness of 400 nm, making the array suitable for on-chip hybrid-CMOS integration and the parallel manipulation of optoelectronic information. We expect these findings to provide possibilities for full-color and aberration-free integral imaging, and we envision that the proposed approach may be potentially applicable in the fields of high-power microlithography, high-precision wavefront sensors, virtual/augmented reality and 3D imaging.

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We demonstrate highly efficient lithium niobate thin film Michelson interferometer modulators with half-wave voltage length product of 1.4 V∙cm. Amorphous silicon grating couplers have been incorporated to achieve a 3.8-dB/port waveguide-fiber coupling loss. Devices with 1-mm phase shifter arms have a footprint of 2.5 mm × 1.7 mm. The demonstrated modulation data rates is up to 35 Gb/s.

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The fluorescence enhancement in an over-etched gold zero-mode waveguide (ZMW) was investigated through both numerical simulation and experiments. Using Cy3 and Cy5 as the fluorescent probes, the simulation showed that the undercut not only enhances the fluorescence signals of both fluorophores, but also greatly improves the radial uniformity of the excitation fields in the ZMW. Furthermore, using a focused-ion-beam tool, we fabricated Au-ZMW arrays with different radius and undercut. The fluorescence enhancement per molecule and the effective excitation volume of the Au-ZMW were then measured as functions of its radial size and over-etching depth by using fluorescence correlation spectroscopy. It was found that the undercut can significantly enhance the fluorescence signal per molecule in the ZMW, but it also slightly increased the excitation volume. Decreasing the radial size of the ZMW can efficiently reduce the excitation volume and also further enhance the fluorescence per molecule. These results together indicate that combining the undercut and reduction of radius of the ZMW can serve as a simple and effective way to essentially improve the performance of an Au-ZMW for single molecule fluorescence detection.

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Surfaces enabling directional drop self-transport have exceptional applications in digital microfluidics, chemical analysis, bioassay, and microreactor technology. While such properties have been obtained by engineering a surface with anisotropic microstructures, a microscopic liquid residue-though it might be invisible macroscopically-is generally left behind the transported drop, resulting in undesired transport loss and severely limiting practical applications of the surface. Here, the origin of microscopic liquid residue is studied by investigating directional drop self-transport on anisotropic surfaces made of radially arranged omniphobic microstripes. It is revealed that the occurrence of a liquid residue is governed by a transport-velocity-dependent dynamic wetting mechanism involving the formation of entrained thin liquid films at high capillary numbers while the local dynamic receding contact angle vanishes. Rayleigh-like breakup of the liquid films leads to the microscopic liquid residue. It is further shown that a liquid-like coating featuring highly flexible molecular chains can effectively suppress the formation of entrained liquid films at high transport velocities, thereby facilitating lossless and fast drop self-transport on anisotropic omniphobic surfaces.

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We demonstrate hybrid amorphous silicon uniform grating couplers for efficient coupling between the standard single-mode fiber and sub-micron lithium niobate waveguides. The grating couplers exhibit coupling efficiency of -3.06 dB and 1-dB bandwidth of 55 nm. The amorphous silicon grating couplers can also provide a universal building block applicable to other photonic platforms such as silicon nitride waveguides, whose moderate refractive index values prevent high efficiency grating couplers to be fabricated in the native waveguide.

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Subwavelength imaging requires the use of high numerical aperture (NA) lenses together with immersion liquids in order to achieve the highest possible resolution. Following exciting recent developments in metasurfaces that have achieved efficient focusing and novel beam-shaping, the race is on to demonstrate ultrahigh-NA metalenses. The highest NA that has been demonstrated so far is NA = 1.1, achieved with a TiO2 metalens and back-immersion. Here, we introduce and demonstrate a metalens with a high NA and high transmission in the visible range, based on crystalline silicon (c-Si). The higher refractive index of silicon compared to TiO2 allows us to push the NA further. The design uses the geometric phase approach also known as the Pancharatnam-Berry (P-B) phase, and we determine the arrangement of nanobricks using a hybrid optimization algorithm (HOA). We demonstrate a metalens with NA = 0.98 in air, a bandwidth (full width at half-maximum, fwhm) of 274 nm, and a focusing efficiency of 67% at 532 nm wavelength, which is close to the transmission performance of a TiO2 metalens. Moreover, and uniquely so, our metalens can be front-immersed into immersion oil and achieve an ultrahigh NA of 1.48 experimentally and 1.73 theoretically, thereby demonstrating the highest NA of any metalens in the visible regime reported to the best of our knowledge. The fabricating process is fully compatible with microelectronic technology and therefore scalable. We envision the front-immersion design to be beneficial for achieving ultrahigh-NA metalenses as well as immersion metalens doublets, thereby pushing metasurfaces into practical applications such as high resolution, low-cost confocal microscopy and achromatic lenses.

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Photonic integrated devices that emit vortex beam carrying orbital angular momentum are becoming key components for multiple applications. Here we propose and demonstrate a high-efficiency vortex beam emitter based on a silicon micro-ring resonator integrated with a metal mirror. Such a compact emitter is capable of generating vortex beams with a high efficiency and small divergence angle. Vector vortex beams of various topological charges are selectively generated by the emitter at different wavelengths with an emission efficiency of up to 37%.

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The epithelial-mesenchymal transition (EMT) is a multifunctional cell process involved in the pathogenesis of numerous conditions, including fibrosis and cancer. Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease characterized by fibroblast accumulation and collagen deposition in the lungs. The fibroblasts involved in this process partially originate from lung epithelial cells via the EMT. Evidence suggests that the EMT contributes to progression, invasion, and metastasis of various types of cancer. We screened a series of 80 compounds for the ability to interfere with the EMT and potentially be applied as a therapeutic for IPF and/or lung cancer. We identified 2-aminopurine (2-AP), a fluorescent analog of guanosine and adenosine, as a candidate in this screen. Herein, we demonstrate that 2-AP can restore E-cadherin expression and inhibit fibronectin and vimentin expression in TGF-ß1-treated A549 lung cancer cells. Moreover, 2-AP can inhibit TGF-ß1-induced metastasis of A549 cells. This compound significantly attenuated bleomycin (BLM)-induced pulmonary inflammation, the EMT, and fibrosis. In addition, 2-AP treatment significantly decreased mortality in a mouse model of pulmonary fibrosis. Collectively, we determined that 2-AP could inhibit metastasis in vitro by suppressing the TGF-ß1-induced EMT and could attenuate BLM-induced pulmonary fibrosis in vivo. Results of this study suggest that 2-AP may have utility as a treatment for lung cancer and pulmonary fibrosis.

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We design and fabricate a low-loss silicon photonic two-dimensional grating coupler that serves to couple light between standard single-mode fibers and single-mode waveguides in the silicon-on-insulator platform and to split both orthogonal polarization states. The efficiency of the fabricated device is enhanced by a backside metal mirror and reaches a record value of -1.8 dB with a 1 dB bandwidth of 32 nm around 1550 nm. The demonstrated coupling efficiency is 2.2 dB better than the conventional two-dimensional grating coupler without a metal mirror.