Sensory neuroimmune signaling in the pathogenesis of Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN).

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening cutaneous reactions often triggered by medications. While the involvement of CD8+ T cells causing keratinocyte death is well recognized, the contribution of neural elements to the persistent skin inflammation has been largely overlooked. OBJECTIVE: To investigate the potential neuroimmune regulation in SJS/TEN. METHODS: Unbiased single-cell RNA sequencing and flow cytometry were performed using circulating CD8+ T cells from healthy controls and patients with SJS/TEN. ELISA and LEGENDplex assays were respectively used to detect neuropeptides and inflammatory mediators. Skin tissues were examined by immunofluorescence staining for neuropeptide-associated nerves and cytokine receptors. Calcium imaging, Smart-seq, and a 3D skin model were employed for cultured human CD8+ T cells. RESULTS: The unbiased RNA-sequencing revealed an upregulation of the receptor for neuropeptide calcitonin gene-related peptide (CGRP), known as RAMP1, in effector CD8+ T cells in SJS/TEN. Increased CGRP+ nerve fibers and CGRP levels, along with upregulated IL-15R and IL-18R on CD8+ T cells, were displayed in the affected skin of SJS/TEN. The CGRP-RAMP1 axis was necessary and sufficient to enhance receptors for IL-15 and IL-18 and cytotoxic activities in CD8+ T cells, ultimately resulting in keratinocyte apoptosis. Calcium influx was detected in CGRP-stimulated CD8+ T cells. HCN2, a hyperpolarization-activated cation channel, was required for this process and the subsequent cytotoxic effects. CONCLUSIONS: Our study highlights the role of neural elements in regulating CD8+ T cell-mediated inflammatory responses and provides new potential translational targets to improve the outcomes of severe cutaneous drug reactions.

CRKL but not CRKII contributes to hemin-induced erythroid differentiation of CML.

Destruction of erythropoiesis process leads to various diseases, including thrombocytopenia, anaemia, and leukaemia. miR-429-CT10 regulation of kinase-like (CRKL) axis involved in development, progression and metastasis of cancers. However, the exact role of miR-429-CRKL axis in leukaemic cell differentiation are still unknown. The current work aimed to uncover the effect of miR-429-CRKL axis on erythropoiesis. In the present study, CRKL upregulation was negatively correlated with miR-429 downregulation in both chronic myeloid leukaemia (CML) patient and CR patient samples. Moreover, CRKL expression level was significantly decreased while miR-429 expression level was increased during the erythroid differentiation of K562 cells following hemin treatment. Functional investigations revealed that overexpression and knockdown of CRKL was remarkably effective in suppressing and promoting hemin-induced erythroid differentiation of K562 cells, whereas, miR-429 exhibited opposite effects to CRKL. Mechanistically, miR-429 regulates erythroid differentiation of K562 cells by downregulating CRKL via selectively targeting CRKL-3'-untranslated region (UTR) through Raf/MEK/ERK pathway. Conversely, CRKII had no effect on erythroid differentiation of K562 cells. Taken together, our data demonstrated that CRKL (but not CRKII) and miR-429 contribute to development, progression and erythropoiesis of CML, miR-429-CRKL axis regulates erythropoiesis of K562 cells via Raf/MEK/ERK pathway, providing novel insights into effective diagnosis and therapy for CML patients.

Prostate cancer microenvironment: multidimensional regulation of immune cells, vascular system, stromal cells, and microbiota.

BACKGROUND: Prostate cancer (PCa) is one of the most prevalent malignancies in males worldwide. Increasing research attention has focused on the PCa microenvironment, which plays a crucial role in tumor progression and therapy resistance. This review aims to provide a comprehensive overview of the key components of the PCa microenvironment, including immune cells, vascular systems, stromal cells, and microbiota, and explore their implications for diagnosis and treatment. METHODS: Keywords such as "prostate cancer", "tumor microenvironment", "immune cells", "vascular system", "stromal cells", and "microbiota" were used for literature retrieval through online databases including PubMed and Web of Science. Studies related to the PCa microenvironment were selected, with a particular focus on those discussing the roles of immune cells, vascular systems, stromal cells, and microbiota in the development, progression, and treatment of PCa. The selection criteria prioritized peer-reviewed articles published in the last five years, aiming to summarize and analyze the latest research advancements and clinical relevance regarding the PCa microenvironment. RESULTS: The PCa microenvironment is highly complex and dynamic, with immune cells contributing to immunosuppressive conditions, stromal cells promoting tumor growth, and microbiota potentially affecting androgen metabolism. Vascular systems support angiogenesis, which fosters tumor expansion. Understanding these components offers insight into the mechanisms driving PCa progression and opens avenues for novel therapeutic strategies targeting the tumor microenvironment. CONCLUSIONS: A deeper understanding of the PCa microenvironment is crucial for advancing diagnostic techniques and developing precision therapies. This review highlights the potential of targeting the microenvironment to improve patient outcomes, emphasizing its significance in the broader context of PCa research and treatment innovation.

Construction of vector vortex beams on hybrid-order Poincaré sphere through highly scattering media.

Vector vortex beams (VVBs) have attracted extensive attention due to their unique properties and their wide applications in fields such as optical manipulation and optical imaging. However, the wavefronts of the vector vortex beams are highly scrambled when they encounter highly scattering media (HSM), such as thick biological tissues, which greatly prevents the applications of VVBs behind HSM. To address this issue, we propose a scheme to construct VVBs of freewill position on the surface of hybrid-order Poincaré sphere (HyOPS) through HSM. With the measurement of two orthogonal scalar transmission matrices, the conjugated wavefronts for constructing orbital angular momentum beams with arbitrary topological charge in right and left circularly polarized states through HSM can be calculated, respectively. When an input wavefront superimposed by the two conjugated wavefronts with an appropriate ratio and phase delay, impinges on the HSM, the desired VVB can be created through HSM. To demonstrate the viability of our scheme, a series of VVBs on different locations of various HyOPSs have been reconstructed through a ZnO scattering layer experimentally. Furthermore, to characterize the polarization distribution of the generated beams, the polarization maps of these beams are derived by measuring the four Stokes parameters, which agree well with the theoretical distributions. This work will promote the applications of VVBs in highly scattering environments.

Tm,Ho:YLF waveguide lasers at 2.05†µm.

In this work, we report on the first, to our knowledge, 2.05-µm laser based on femtosecond-laser direct written (FsLDW) Tm,Ho:YLF cladding waveguides. A channel waveguide with a 90-µm diameter "fiber-like" low-index cladding is fabricated in a 6 at. % Tm3+, 0.4 at. % Ho3+:LiYF4 crystal by FsLDW. Pumped by Ti:sapphire laser at 795.1 nm, the fabricated waveguide supports efficient lasing oscillation at 2050 nm with a maximum output power of 47.5 mW, a minimum lasing threshold of 181 mW, and a slope efficiency of 20.1%. The impacts of cavity conditions and polarizations of the pump light on the obtained lasing performance are well studied. The experimental results obtained in this study demonstrate the great potential of utilizing Tm,Ho:YLF and FsLDW for the development of durable mid-infrared lasers featuring compact designs.

Construction of an Injectable Composite Double-Network Hydrogel as a Liquid Embolic Agent.

Conventional embolists disreputably tend to recanalization arising from the low filling ratio due to their rigidity or instability. As a result, intelligent hydrogels with a tunable modulus may meaningfully improve the therapeutic efficacy. Herein, an injectable composite double-network (CDN) hydrogel with high shear responsibility was prepared as a liquid embolic agent by cross-linking poly(vinyl alcohol) (PVA) and carboxymethyl chitosan (CMC) via dynamic covalent bonding of borate ester and benzoic-imine. A two-dimensional nanosheet, i.e., layered double hydroxide (LDH), was incorporated into the network through physical interactions which led to serious reduction of yield stress for the injection of the hydrogel and the capacity for loading therapeutic agents like indocyanine green (ICG) and doxorubicin (DOX) for the functions of photothermal therapy (PTT) and chemotherapy. The CDN hydrogel could thus be transported through a thin catheter and further in situ strengthened under physiological conditions, like in blood, by secondarily cross-linking with phosphate ions for longer degradation duration and better mechanical property. These characteristics met the requirements of arterial interventional embolization, which was demonstrated by renal embolism operation on rabbits, and meanwhile favored the inhibition of subcutaneous tumor growth on an animal model. Therefore, this work makes a breakthrough in the case of largely reducing the embolism risks, thus affording a novel generation for interventional embolization.

FKF1b controls reproductive transition associated with adaptation to geographical distribution in maize.

Maize (Zea mays subspecies mays) is an important commercial crop across the world, and its flowering time is closely related to grain yield, plant cycle and latitude adaptation. FKF1 is an essential clock-regulated blue-light receptor with distinct functions on flowering time in plants, and its function in maize remains unclear. In this study, we identified two FKF1 homologs in the maize genome, named ZmFKF1a and ZmFKF1b, and indicated that ZmFKF1a and ZmFKF1b independently regulate reproductive transition through interacting with ZmCONZ1 and ZmGI1 to increase the transcription levels of ZmCONZ1 and ZCN8. We demonstrated that ZmFKF1b underwent artificial selection during modern breeding in China probably due to its role in geographical adaptation. Furthermore, our data suggested that ZmFKF1bHap_C7 may be an elite allele, which increases the abundance of ZmCONZ1 mRNA more efficiently and adapt to a wider range of temperature zone than that of ZmFKF1bHap_Z58 to promote maize floral transition. It extends our understanding of the genetic diversity of maize flowering. This allele is expected to be introduced into tropical maize germplasm to enrich breeding resources and may improve the adaptability of maize at different climate zones, especially at temperate region.

Polymer-Protein Assemblies with Tunable Vesicular and Hierarchical Nanostructures.

The construction of variable structured multi-protein nano-assemblies is of great interest for the development of protein-based therapeutic systems. This study showcases the synthesis of polymer-protein assemblies with tunable structure like single- and multi-layer polymer-crosslinked protein vesicles, Janus protein vesicles and other hierarchical-structured assemblies by utilizing a dynamic template-assistant intermittent-assembly approach. The generalization of the methodology helps the protein assemblies to gain notable functional complexity. And we demonstrate compelling evidence highlighting the substantial impact of the topological morphology of protein nanoaggregates on their cellular uptake capacity.

Ultrafast laser fabrication of efficient polarization-insensitive demultiplexer circuit in YAG crystal.

Wavelength division multiplexing is a widely used monolithic device with modulating light sources at different wavelengths based on a designed configuration. In this paper, we report an in-chip demultiplexer with a simple design operating at 532/1064 nm in pure YAG crystal. The device is fabricated by femtosecond laser direct writing inside the transparent substrate with just a width of 36 µm. The compact structure is designed based on the principle of self-imaging, and the propagation features have been simulated by utilizing the beam propagation method. The performance of this wavelength demultiplexer has been investigated through an end-face coupling system, which proves the device can separate 532 nm and 1064 nm light into two discrete waveguides polarization-insensitively with an extinction ratio as high as 13 dB. These superior performances manifest this exquisite device can emerge into kinds of photonic applications in the future. Also, this work further proves that femtosecond laser direct writing technology has irreplaceable advantages in processing micro-nano devices in transparent materials for in-chip integration.

Second harmonic generation in plasmonic metasurfaces enhanced by symmetry-protected dual bound states in the continuum.

We numerically investigate linear and nonlinear optical responses in metasurfaces consisting of Au double-gap split ring resonators (DSRRs). Symmetry-protected dual bound states in the continuum (BICs) in such plasmonic metasurfaces are observed at the near-infrared optical regime. Efficient second harmonic generation (SHG) is obtained at the quasi-BIC models due to the symmetry broken. The optimized SHG responses are obtained at the critical couplings between radiation and nonradiation processes at the linearly x- and y-polarized light, respectively. High conversion efficiency of SHG of a value 10-6 is arrived at the fundamental intensity of 10 GW/cm2 at the quasi-BIC wavelength under the y-polarized illumination. Large extrinsic and tunable chirality of linear and nonlinear optical responses empowered by quasi-BICs is acquired in asymmetry metasurfaces at oblique circularly polarized incidence. The results indicate that the plasmonic metasurfaces of symmetry-protected BICs at the near-infrared optical regime have great potential applications in the on-chip efficient frequency conversion, and the linear and nonlinear chiral manipulation.

Nd:YSAG waveguide-grating vortex laser: design and implementation.

In this work, we fabricate a hybrid waveguide-grating vortex laser in Nd:YSAG by using femtosecond laser direct writing (FsLDW). The detailed parameters of the hybrid structure are fixed by optical simulation. In experiments, an efficient vortex beam is produced in the passive operation at 1064 nm. Under optical pumping at 808 nm, a dual-wavelength waveguide laser at 1060/1062 nm as well as a waveguide-grating vortex laser at 1060 nm are obtained. The laser performance and diffraction properties of the generated vortex laser are detailed, studied, and discussed, providing meaningful reference results toward the practical applications of FsLDW and waveguide-grating structures in integrated photonics.

Enantioselective Michael Addition of Malononitrile to Unsaturated Ketones Catalyzed by Rare-Earth Metal Amides RE[N(SiMe3)2]3 with Phenoxy-Functionalized TsDPEN Ligands.

The catalytic enantioselective Michael addition of α,ß-unsaturated ketones with malononitrile was well established using rare-earth metal amides RE[N(SiMe3)2]3 (RE = Y, Eu, Sm, Nd, La) with chiral phenoxy-functionalized TsDPEN ligands. The combination of lanthanum amide La[N(SiMe3)2]3 and chiral TsDPEN ligand H3L1 [H3L1 = N-((1R,2R)-2-((3,5-di-tert-butyl-2-hydroxybenzyl)amino)-1,2-diphenylethyl)-4-methylbenzenesulfonamide] in a 1:1.5 molar ratio was proved to be the optimal partner in THF, which provided the desired ß-carbonyl dinitriles in excellent yields and good to high enantioselectivities after 12 h at -15 °C.

Association Between Smoking Behavior and Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis.

INTRODUCTION: To systematically review the association between smoking behavior and obstructive sleep apnea (OSA). AIMS AND METHODS: PubMed, Medline, the Cochrane Library, EMBASE, and Scopus databases were used to conduct this review. The two researchers independently screened the literatures, conducted the quality assessment, and data extraction according to the inclusion and exclusion criteria. The RevMan 5.3 was used to analysis the apnea hypopnea index (AHI) index, min saturation of oxyhemoglobin (SaO2), Epworth Sleepiness Scale (ESS) score, and oxygen desaturation index (DOI) and publication bias analysis to assess the effect of smoking on OSA patients. Furthermore, we performed subgroup of the severity of OSA, different countries of sample origin (western countries or eastern countries), and pack-years (PYs < 10 or PYs ≥ 20) to analyze the heterogeneity. RESULTS: Thirteen studies were included in this analysis that conformed to inclusion criteria and exclusion criteria. Totally 3654 smokers and 9796 non-smokers have participated. The meta-analysis of 13 studies demonstrated that AHI levels were significantly higher in smoker group compared with non-smoker, ESS scores were also significantly higher in smoker group compared with non-smoker, min SaO2 levels were obviously lower in smoker group compared with non-smoker, however, DOI levels hadn't significantly different between two groups. The subgroup analysis showed that there was an association between severe OSA, eastern countries, pack-years, and smoking. CONCLUSIONS: Smoking behavior is a significant association with OSA. Heavy smokers with histories of more than 20 PYs were at a higher risk of OSA. Moreover, patient with severe OSA exhibited a significantly association with smoking compared with patients with mild or moderate OSA. IMPLICATIONS: The relationship between smoking and OSA was controversial, especially, whether smoking increase or aggravate the risk of OSA. In our review and meta-analysis, we demonstrated that smoking behavior is a significant association with OSA. Heavy smokers with histories of more than 20 PYs were at a higher risk of OSA. Moreover, patient with severe OSA exhibited a significant association with smoking compared with patients with mild or moderate OSA. More prospective long-term follow-up studies about effect of quit smoking on OSA are recommended to establish the further relationship.

Microcirculation No-Reflow Phenomenon after Acute Ischemic Stroke.

BACKGROUND: The no-reflow phenomenon refers to a failure to restore normal cerebral microcirculation despite brain large artery recanalization after acute ischemic stroke, which was observed over 50 years ago. SUMMARY: Different mechanisms contributing to no-reflow extend across the endovascular, vascular wall, and extravascular factors. There are some clinical tools to evaluate cerebral microvascular hemodynamics and represent biomarkers of the no-reflow phenomenon. As substantial experimental and clinical data showed that clinical outcome was better correlated with reperfusion status rather than recanalization in patients with ischemic stroke, how to address the no-reflow phenomenon is critical. But effective treatments for restoring cerebral microcirculation have not been well established until now, so there is an urgent need for novel therapeutic perspectives to improve outcomes after recanalization therapies. CONCLUSION: Here, we review the occurrence of the no-reflow phenomenon after ischemic stroke and discuss its impact, detection method, and therapeutic strategies on the course of ischemic stroke, from basic science to clinical findings.

Robust Interval Prediction of Intermittent Demand for Spare Parts Based on Tensor Optimization.

Demand for spare parts, which is triggered by element failure, project schedule and reliability demand, etc., is a kind of sensing data to the aftermarket service of large manufacturing enterprises. Prediction of the demand for spare parts plays a crucial role in inventory management and lifecycle quality management for the aftermarket service of large-scale manufacturing enterprises. In real-life applications, however, demand for spare parts occurs randomly and fluctuates greatly, and the demand sequence shows obvious intermittent distribution characteristics. Additionally, due to factors such as reporting mistakes made by personnel or environmental changes, the actual data of the demand for spare parts are prone to abnormal variations. It is thus hard to capture the evolutional pattern of the demand for spare parts by traditional time series forecasting methods. The reliability of prediction results is also reduced. To address these concerns, this paper proposes a tensor optimization-based robust interval prediction method of intermittent time series for the aftersales demand for spare parts. First, using the advantages of tensor decomposition to effectively mine intrinsic information from raw data, a sequence-smoothing network based on tensor decomposition and a stacked autoencoder is proposed. Tucker decomposition is applied to the hidden features of the encoder, and the obtained core tensor is reconstructed through the decoder, thus allowing us to smooth outliers in the original demand sequence. An alternating optimization algorithm is further designed to find the optimal sequence feature representation and tensor decomposition factors for the extraction of the evolutionary trend of the intermittent series. Second, an adaptive interval prediction algorithm with a dynamic update mechanism is designed to obtain point prediction values and prediction intervals for the demand sequence, thereby improving the reliability of the forecast. The proposed method is validated using the actual aftersales data from a large engineering manufacturing enterprise in China. The experimental results demonstrate that, compared with typical time series prediction methods, the proposed method can effectively grab the evolutionary trend of various intermittent series and improve the accuracy of predictions made with small-sample intermittent series. Moreover, the proposed method provides a reliable elastic prediction interval when distortion occurs in the prediction results, offering a new solution for intelligent planning decisions related to spare parts in practical maintenance.

Femtosecond laser writing of waveguides in zinc oxide crystals: fabrication and mode modulation.

We report for the first time on optical waveguides in zinc oxide (ZnO) crystals fabricated by femtosecond laser direct writing. The confocal Raman microscopy under 488 nm laser excitation is used to investigate the micro-modifications of the laser irradiation, and guiding properties are studied via the end-face coupling at 632.8 nm. The mode modulation has been achieved by the adjustment of laser writing parameters. A minimum propagation loss of ∼6 dB/cm is obtained for the double-line waveguide structures. A Y-branch waveguide beam splitter is also fabricated, reaching a splitting ratio of nearly 1:1. The original optical properties in the guiding region have been well preserved, according to the confocal Raman investigation, which suggests potential applications of the ZnO waveguides for integrated photonics and nonlinear optics.

Simultaneous spatial and temporal focusing optical vortex pulses for micromachining through optically transparent materials.

We introduce the optical vortex beam into simultaneous spatial and temporal focusing (SSTF) technique, and theoretically and experimentally demonstrate the local control of peak intensity distribution at the focus of a simultaneous spatiotemporally focused optical vortex (SSTF OV) beam. To avoid nonlinear self-focusing in the conventional focusing scheme, a spatiotemporally focused femtosecond laser vortex beam was employed to achieve doughnut-shaped ablation and high aspect ratio (∼28) microchannels on the back surface of 3 mm thick soda-lime glass and fused silica substrates.

Unique beam deflection based on dynamic polarized nano-domains in Cu-doped KTN.

In this report, we successfully implement a unique cross-field beam deflector by exploiting the modulation of a one-dimensional refractive index in a copper-doped potassium tantalite niobite crystal. A theoretical model is established based on an electrostrictive effect regulated by the dynamic polarized nano-domains to explicate the mechanism of the abnormal beam deflection which is perpendicular to the applied electric field. Experimental results agree well with our theoretical deduction while validating the interactions between the dynamic polarized nano-domains and the applied electric field. Our findings will break the limitation of conventional electro-optic deflectors, paving the way to develop promising optical functional devices with a large field-of-view scanning angle and ultra-low driving voltage.

Mode-controllable waveguide fabricated by laser-induced phase transition in KTN.

We report the fabrication of a hexagonal cladding waveguide by femtosecond laser direct writing (FLDW) in a potassium tantalate niobate (KTN) crystal with a large electric-optical effect. Confocal micro-Raman results show the laser-induced phase transition occurs in the filament areas during the waveguide fabrication. The small filaments can strongly confine the polar nanoregions especially in its ferroelectric state to enhance the waveguide birefringence, enabling excellent polarization maintaining features for both TE and TM-polarized light propagations. The temperature-dependent phase transition allows for an active control of waveguide polarization modes as well as a switchable polarization-maintaining feature.

Treatment of refractory bullous pemphigoid with IFN-α-2b: A case report.

We reported a patient with refractory bullous pemphigoid (BP), who had a higher level of eosinophils and serum IgE. The case showed less response to various therapies. Edematous erythema and new blisters appeared constantly. Considering IFN-α-2b treatment could significantly decrease blood eosinophils, we therefore expected that IFN-α-2b could be effective in the treatment of BP. After treated with IFN-α-2b, the patient's good response to the treatment suggested our hypothesis.