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In recent years, in vivo retinal imaging, which provides non-invasive, real-time, and longitudinal information about biological systems and processes, has been increasingly applied to obtain an objective assessment of neural damage in eye diseases. Ex vivo confocal imaging of the same retina is often necessary to validate the in vivo findings especially in animal research. In this study, we demonstrated a method for aligning an ex vivo confocal image of the mouse retina with its in vivo images. A new clinical-ready imaging technology called visible light optical coherence tomography fibergraphy (vis-OCTF) was applied to acquire in vivo images of the mouse retina. We then performed the confocal imaging of the same retina as the "gold standard" to validate the in vivo vis-OCTF images. This study not only enables further investigation of the molecular and cellular mechanisms but also establishes a foundation for a sensitive and objective evaluation of neural damage in vivo.

Poor stability retards the industrialization of perovskite solar cells (PSCs). One of the effective ways to solve this issue is to modify the perovskite surface to improve the efficiency and stability of the PSCs. Herein, we synthesized CuFeS 2 nanocrystals and applied them to modify the perovskite surface. The efficiency of the PSCs with CuFeS 2 modification is improved to 20.17% from 18.64% for the control devices. Some investigations demonstrate that the CuFeS 2 modification passivates the perovskite surface defects and induces better energy band arrangement. Furthermore, the stability of the PSCs with CuFeS 2 modification is improved compared with the devices without CuFeS 2 modification. The efficiency of the PSCs with CuFeS 2 modification maintains 93% of its initial value, whereas that of the devices without CuFeS 2 modification decreases to 61% of the initial value. This work demonstrates that CuFeS 2 is a novel material used as a modification layer to enhance the efficiency and stability of the PSCs.

Photoacoustic (PA) imaging enables noninvasive volumetric imaging of biological tissues by capturing the endogenous optical absorption contrast. Conventional ultrasound detectors using piezoelectric materials have been widely used for transducing ultrasound signals into the electrical signals for PA imaging reconstruction. However, their inherent limitations in detection bandwidth and sensitivity per unit area have unfortunately constrained the performance of PA imaging. Optical based ultrasound detection methods emerge to offer very promising solutions. In particular, polymer micro-ring resonators (MRRs) in the form of integrated photonic circuits (IPC) enable significant reduction for the sensing area to 80 μm in diameter, while maintaining highly sensitive ultrasound detection with noise equivalent pressure (NEP) of 0.49 Pa and a broad detection frequency range up to 250 MHz. The continued engineering innovation has further transformed MRRs to be transparent to the light and thus, opens up a wide range of applications, including multi-modality optical microscope with isometric resolution, PA endoscope, photoacoustic computed tomography (PACT), and more. This review article summarizes and discusses the evolution of polymer MRR design and the associated nanofabrication process for improving the performance of ultrasound detection. The resulting novel imaging applications will also be reviewed and discussed., (© 2023. The Author(s).)

Perfluorinated compounds, especially Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), are widely detected in water environments in China. Considering the potential health risks of drinking water exposure routes, PFOA and PFOS have been added to the water quality reference index of the newly issued "Standards for Drinking Water Quality (GB5749-2022)", with limit values of 40 and 80 ng/L, respectively. This study analyzed and discussed the relevant technical contents for determining the limits of the hygiene standard, including the environmental existence level and exposure status of PFOA and PFOS, health effects, derivation of safety reference values, and determination of hygiene standard limits. It also proposed prospects for the future direction of formulating drinking water standards.

Background: Increasing evidence indicates that the tumor microenvironment (TME) is a crucial determinant of cancer progression. However, the clinical and pathobiological significance of stromal signatures in the TME, as a complex dynamic entity, is still unclear in esophageal squamous cell carcinoma (ESCC)., Methods: Herein, we used single-cell transcriptome sequencing data, imaging mass cytometry (IMC) and multiplex immunofluorescence staining to characterize the stromal signatures in ESCC and evaluate their prognostic values in this aggressive disease. An automated quantitative pathology imaging system determined the locations of the lamina propria, stroma, and invasive front. Subsequently, IMC spatial analyses further uncovered spatial interaction and distribution. Additionally, bioinformatics analysis was performed to explore the TME remodeling mechanism in ESCC. To define a new molecular prognostic model, we calculated the risk score of each patient based on their TME signatures and pTNM stages., Results: We demonstrate that the presence of fibroblasts at the tumor invasive front was associated with the invasive depth and poor prognosis. Furthermore, the amount of α-smooth muscle actin (α-SMA) + fibroblasts at the tumor invasive front positively correlated with the number of macrophages (MØs), but negatively correlated with that of tumor-infiltrating granzyme B + immune cells, and CD4 + and CD8 + T cells. Spatial analyses uncovered a significant spatial interaction between α-SMA + fibroblasts and CD163 + MØs in the TME, which resulted in spatially exclusive interactions to anti-tumor immune cells. We further validated the laminin and collagen signaling network contributions to TME remodeling. Moreover, compared with pTNM staging, a molecular prognostic model, based on expression of α-SMA + fibroblasts at the invasive front, and CD163 + MØs, showed higher accuracy in predicting survival or recurrence in ESCC patients. Regression analysis confirmed this model is an independent predictor for survival, which also identifies a high-risk group of ESCC patients that can benefit from adjuvant therapy., Conclusions: Our newly defined biomarker signature may serve as a complement for current clinical risk stratification approaches and provide potential therapeutic targets for reversing the fibroblast-mediated immunosuppressive microenvironment., (© 2023. The Author(s).)

An advanced optical terahertz (THz) fingerprint sensor based on coherent perfect absorption (CPA) is proposed. Based on a one-dimensional layered photonic structure, the sensor contains a cavity that is developed for THz fingerprint measurement. Utilizing the magneto-optical effect of magnetized InSb, CPA is excited in the structure of the sensor. Taking α-lactose as exemplar material, this numerical simulation is integrated with a Drude-Lorentz model. The transfer matrix method (TMM) is used to calculate the sensitivity ( S ), linear range (LR), quality ( Q ), the figure of merit (FOM*), and detection limit (DL) theoretically. Employing the amplitude modulation detection method, the qualitative and quantitative analysis of the α-lactose thickness of 0-0.5 μm could be realized. Because of the fragility of CPA, the S is 0.78255 μm -1 , the value of average Q is up to 8019.2, the value of average FOM* is 13 234.4 (THz μm) -1 , and the lower DL is 4.21 × 10 -6 . Moreover, the evolutions of ensemble-averaged absorption in the vicinity of the absorption peaks for different types of disorder effects are considered, which will be considered in the fabrication of sensors.

To date there have been many studies on multi-channel absorbers for conventional photonic crystals (PCs). However, the number of absorption channels is small and uncontrollable, which cannot satisfy applications such as multispectral or quantitative narrowband selective filters. To address these issues, a tunable and controllable multi-channel time-comb absorber (TCA) based on continuous photonic time crystals (PTCs), is theoretically proposed. Compared with conventional PCs with fixed refractive index (RI), this system forms a stronger local electric field enhancement in the TCA by absorbing externally modulated energy, resulting in sharp multi-channel absorption peaks (APs). Tunability can be achieved by adjusting the RI, angle, and time period unit (T) of the PTCs. Diversified tunable methods allow the TCA to have more potential applications. In addition, changing T can adjust the number of multi-channels. More importantly, changing the primary term coefficient of n 1 (t) of PTC 1 can control the number of time-comb absorption peaks (TCAPs) in multi-channels within a certain range, and the mathematical relationship between the coefficients and the number of multiple channels is summarized. This will have potential applications in the design of quantitative narrowband selective filters, thermal radiation detectors, optical detection instruments, etc.

Ultrasound-microwave combined extraction (UMCE), gradient ethanol precipitation, chemical characterization, and antioxidant and hypoglycemic activities of Lycium barbarum leaf polysaccharides (LLP) were systematically studied. The optimal conditions for UMCE of LLP achieved by response surface method (RSM) were as follows: microwave time of 16 min, ultrasonic time of 20 min, particle size of 100 mesh, and ratio of liquid to solid of 55:1. Three novel polysaccharide fractions (LLP 30 , LLP 50 , LLP 70 ) with different molecular weights were obtained by gradient ethanol precipitation. Polysaccharide samples exhibited scavenging capacities against ABTS and DPPH radicals and inhibitory activities against α-glucosidase and α-amylase. Among the three fractions, LLP 30 possessed relatively high antioxidant and hypoglycemic activities in vitro, which showed a potential for becoming a nutraceutical or a phytopharmaceutical for prevention and treatment of hyperglycemia or diabetes.

Previous studies have shown mitochondrial dysfunction in various acute kidney injuries and chronic kidney diseases. Lipoic acid exerts potent effects on oxidant stress and modulation of mitochondrial function in damaged organ. In this study we investigated whether alpha lipoamide (ALM), a derivative of lipoic acid, exerted a renal protective effect in a type 2 diabetes mellitus mouse model. 9-week-old db/db mice were treated with ALM (50 mg·kg -1 ·d -1 , i.g) for 8 weeks. We showed that ALM administration did not affect blood glucose levels in db/db mice, but restored renal function and significantly improved fibrosis of kidneys. We demonstrated that ALM administration significantly ameliorated mitochondrial dysfunction and tubulointerstitial fibrotic lesions, along with increased expression of CDX2 and CFTR and decreased expression of β-catenin and Snail in kidneys of db/db mice. Similar protective effects were observed in rat renal tubular epithelial cell line NRK-52E cultured in high-glucose medium following treatment with ALM (200 μM). The protective mechanisms of ALM in diabetic kidney disease (DKD) were further explored: Autodock Vina software predicted that ALM could activate RXRα protein by forming stable hydrogen bonds. PROMO Database predicted that RXRα could bind the promoter sequences of CDX2 gene. Knockdown of RXRα expression in NRK-52E cells under normal glucose condition suppressed CDX2 expression and promoted phenotypic changes in renal tubular epithelial cells. However, RXRα overexpression increased CDX2 expression which in turn inhibited high glucose-mediated renal tubular epithelial cell injury. Therefore, we reveal the protective effect of ALM on DKD and its possible potential targets: ALM ameliorates mitochondrial dysfunction and regulates the CDX2/CFTR/β-catenin signaling axis through upregulation and activation of RXRα. Schematic figure illustrating that ALM alleviates diabetic kidney disease by improving mitochondrial function and upregulation and activation of RXRα, which in turn upregulated CDX2 to exert an inhibitory effect on β-catenin activation and nuclear translocation. RTEC renal tubular epithelial cell. ROS Reactive oxygen species. RXRα Retinoid X receptor-α. Mfn1 Mitofusin 1. Drp1 dynamic-related protein 1. MDA malondialdehyde. 4-HNE 4-hydroxynonenal. T-SOD Total-superoxide dismutase. CDX2 Caudal-type homeobox transcription factor 2. CFTR Cystic fibrosis transmembrane conductance regulator. EMT epithelial mesenchymal transition. α-SMA Alpha-smooth muscle actin. ECM extracellular matrix. DKD diabetic kidney disease. Schematic figure was drawn by Figdraw ( www.figdraw.com )., (© 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Purpose: We developed a new analytic tool based on visible-light optical coherence tomography fibergraphy (vis-OCTF) to longitudinally track individual axon bundle transformation as a new in vivo biomarker for retinal ganglion cell (RGC) damage., Methods: After acute optic nerve crush injury (ONC) in mice, we analyzed four parameters: lateral bundle width, axial bundle height, cross-sectional area, and the shape of individual bundles. We next correlated the morphological changes in RGC axon bundles with RGC soma loss., Results: We showed that axon bundles became wider and taller at three days post ONC (pONC), which correlated with about 15% RGC soma loss. At six days pONC, axon bundles showed a significant reduction in lateral width and cross-sectional area, followed by a reduction in bundle height at nine days pONC. Bundle shrinking at nine days pONC correlated with about 68% RGC soma loss. Both experimental and simulated results suggested that the cross-sectional area of individual RGC axon bundles is more sensitive than bundle width and height to indicate RGC soma loss., Conclusions: This study is the first to track and quantify individual RGC axon bundles in vivo after ONC injury., Translational Relevance: Recognizing RGC loss at its earliest stage is crucial for disease diagnosis and treatment. However, current clinical methods to detect the functional and structural changes in the inner retina are not sensitive enough to directly assess RGC health. In this study, we developed vis-OCTF-based parameters to track RGC damage, making possible to establishing a quantifiable biomarker for glaucoma.

The anapole mode, in which a distinct radiationless electromagnetic (EM) response in artificial media can be achieved, has attracted significant attention and been regarded as a promising candidate to initiate novel avenues to control the intrinsic radiative losses in nanophotonics and plasmonics, whose current research studies mainly focus on the manipulation of the one-directional incident wave. To exploit the propagation characteristic of incident waves in anapole-excited (AE) media, a set of terahertz (THz) multifunctional Janus metastructures (JMSs) for the opposite linear-polarized (LP) light excitation is presented in this paper. By introducing the directional-selective spoof surface plasmon polariton (SSPP) excited by anapole mode, a metastructure rasorber (MSR) possessing an absorption band of 2-3.08 THz (42.5%) and a co-polarized transmission window of 3.77-5.55 THz (38.2%) for the forward normal-incident LP wave is attained. Furthermore, the integration of the MSR and a polarization-conversation structure (PCS) can be used to fabricate a multifunctional Janus metadevice thus achieving the integration of EM energy harvesting, the co-polarized transmission, and cross-polarized reflection of light with opposite propagation directions, i.e. , an absorption band of 2.14-3.09 THz (36.3%) for the forward normal-incident LP wave, and a cross-polarized reflection band of 2.08-3.03 THz (37.2%) for the backward vertical-incident LP wave, while attaining an identical co-polarized transmission window of 3.95-5.2 THz (27.3%). Moreover, by utilizing the substantial field-localization properties of anapole modes supported by the nested opposite-directional SSPP with different sizes, the Janus metastructure absorber (JMA) can achieve non-overlapped absorption bands of 2.02-2.84 THz (33.7%) and 2.88-4.58 THz (45.6%) for the bidirectional normal-incident LP waves, respectively. A series of passive JMSs based on the anapole modes excited by the opposite-directional incident waves significantly extend the theoretical framework and application field of multipole electrodynamics, especially aimed at directional-selective management.

Background: Retinal oxygen saturation (sO 2 ) provides essential information about the eye's response to pathological changes that can result in vision loss. Visible-light optical coherence tomography (vis-OCT) is a noninvasive tool that has the potential to measure retinal sO 2 in a clinical setting. However, its reliability is currently limited by unwanted signals referred to as spectral contaminants (SCs), and a comprehensive strategy to isolate true oxygen-dependent signals from SCs in vis-OCT is lacking., Methods: We develop an adaptive spectroscopic vis-OCT (ADS-vis-OCT) technique that can adaptively remove SCs and accurately measure sO 2 under the unique conditions of each vessel. We also validate the accuracy of ADS-vis-OCT using ex vivo blood phantoms and assess its repeatability in the retina of healthy volunteers., Results: In ex vivo blood phantoms, ADS-vis-OCT agrees with a blood gas machine with only a 1% bias in samples with sO 2 ranging from 0% to 100%. In the human retina, the root mean squared error between sO 2 values in major arteries measured by ADS-vis-OCT and a pulse oximeter is 2.1% across 18 research participants. Additionally, the standard deviations of repeated ADS-vis-OCT measurements of sO 2 values in smaller arteries and veins are 2.5% and 2.3%, respectively. Non-adaptive methods do not achieve comparable repeatabilities from healthy volunteers., Conclusions: ADS-vis-OCT effectively removes SCs from human images, yielding accurate and repeatable sO 2 measurements in retinal arteries and veins with varying diameters. This work could have important implications for the clinical use of vis-OCT to manage eye diseases., (© 2023. The Author(s).)

Objective: Immunogenic cell death (ICD) of tumor cells is characterized by the induction of adaptive and innate immune responses, which in turn activates the immune surveillance and improves the efficacy of immunotherapy. In this study, we aimed to investigate the effect of ICD on the prognosis and the efficacy of immunotherapy in patients with triple-negative breast cancer (TNBC)., Methods: TNBC samples from The Cancer Genome Atlas-Breast Cancer (TCGA-BRCA) dataset were divided into two subtypes (ICD-high and ICD-low) based on the ICD status by using the consensus clustering method, and their genomic landscape and immune landscape were delineated. Furthermore, we established an ICD-related prognostic model to predict the efficacy of immunotherapy and the survival of TNBC., Results: Our study showed that a poor prognosis of TNBC was associated with ICD-high subtype, while a favorable outcome was associated with ICD-low subtype. The immune landscape profiling results revealed that ICD-high subtype presented an immune-hot phenotype, whereas ICD-low subtype was associated with an immune-cold phenotype. Furthermore, our prognostic model predicted that the high-risk score group had a poor overall survival (OS), which was consistent with the actual data in the Gene Expression Omnibus (GEO) dataset. We also used tumor immune dysfunction and exclusion (TIDE) to determine the predictive significance of our ICD risk signature in immunotherapy efficacy, and found that ICD high-risk group had the highest response rate to immunotherapy in the immunotherapy response group., Conclusion: Our results reveal a correlation between ICD status and alterations in the tumor immune microenvironment in patients with TNBC. This finding might help guide clinicians in immunotherapy application for TNBC patients., Competing Interests: None., (AJTR Copyright © 2023.)

Li-rich Mn-based layered oxides (LLOs) are one of the most promising cathode materials, which have exceptional anionic redox activity and a capacity that surpasses 250 mA h/g. However, the change from a layered structure to a spinel structure and unstable anionic redox are accompanied by voltage attenuation, poor rate performance, and problematic capacity. The technique of stabilizing the crystal structure and reducing the surface oxygen activity is proposed in this paper. A coating layer and highly concentrated oxygen vacancies are developed on the material's surface, according to scanning electron microscopy, transmission electron microscopy, and X-ray photoelectron spectroscopy. In situ EIS shows that structural transformation and oxygen release are inhibited during the first charge and discharge. Optimized 3@LRMA has an average attenuation voltage of 0.55 mV per cycle (vs 1.7 mV) and a capacity retention rate of 93.4% after 200 cycles (vs 52.8%). Postmortem analysis indicates that the successful doping of Al ions into the crystal structure effectively inhibits the structural alteration of the cycling process. The addition of oxygen vacancies reduces the surface lattice's redox activity. Additionally, surface structure deterioration is successfully halted by N- and Cl-doped carbon coating. This finding highlights the significance of lowering the surface lattice oxygen activity and preventing structural alteration, and it offers a workable solution to increase the LLO stability.

Purpose: Genotyping is fundamental in papillary thyroid cancer (PTC) and helps to enhance diagnosis and prognosis and determine appropriate treatments. The phenotype-genotype association in PTC was previously studied, with BRAF V600E characterizing classic PTC and tall-cell PTC and RAS mutations characterizing follicular-variant PTC. In clinic, some non-classical histological subtypes of PTC were also identified, however, their genotype remains unclear. In this study, we collected samples of these non-classical PTC after the exclusion of classic phenotypes and examined their phenotypes, genotype and the relationship between phenotype and genotype., Methods: We screened out non-classical PTC by excluding classical PTC from 1,059 different thyroid samples, and a total of 24 cases was obtained and described from the morphological features, which is rare in differentiated PTC. DNA/RNA sequencing was performed using 18 available samples to describe the genetic features., Results: PTC with the non-classical phenotype were characterized cuboidal to low columnar tumor cells with subtle nuclear features of PTC and without discernible nuclear elongation, concurrently with dense microfollicles, delicate papillae or solid nodules with delicate fibrovascular cores. They were associated with lymphatic vessel invasion (P<0.001) but not with a worse prognosis (P=0.791). Gene fusions were identified in 14 of 18 (77.8%) cases, including eight fusions of NTRK and six fusions of RET . The high percentage of fusions in this papillary thyroid cancer subgroup suggested a correlation of gene fusions with the phenotype that does not belong to the BRAF V600E-mutant or RAS -mutant group., Conclusions: Our study retrospectively screened a large cohort of different thyroid tissue samples, and presented the histopathological and genetic features of a non-classical phenotype of PTC from 24 patients. It may contribute to diagnose in PTC, and patients of these non-classical phenotype may benefit from targeted therapy, compared to a natural patient cohort without selection., Competing Interests: W-RW, J-HZ, Y-SH, JC, T-HM, X-YZ are the employees of Genetron Health Beijing Technology, Co. Ltd., Beijing, China. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2023 Zhou, Wang, Zhang, Gao, Wang, Zhu, Han, Chen, Ma, Zhang and Teng.)

It is critical to accurately align a quantum photon detector such as a superconducting transition-edge sensor (TES) to an optical fiber in order to optimize its detection efficiency. Conventionally, such alignment requires advanced infrared imaging equipment or sophisticated microfabrication. We introduce a novel technique based on the simple idea of reflected wave intensity measurement which allows to determine the boundary of the sensor and align it accurately with the fiber. By routing a light wave through an optical fiber for normal incidence on the surface of the sensor chip, and separating the reflected wave coupled back into the fiber from the input signal with a circulator, we can observe the variation in the reflected wave intensity when the beam spot of the fiber crosses the boundary between the sensor and substrate that have different reflectivity, and adjust the position of the fiber such that its output falls on the sensor. We evaluate quantitatively the precision of our alignment method, as well as the conditions that must be met to avoid photon loss caused by light beam divergence. After demonstrating the working principle of our scheme and verifying the alignment result experimentally, we employ it for efficient input signal coupling to a TES device, which is used for photon-number-resolving measurement to showcase the successful application of our alignment method in practice. Relying on only ordinary and widely used optical elements that are easy to operate and low in cost, our solution is much less demanding than conventional methods. Dramatically easier to implement and not restricted by the detection mechanism of the sensor, it is accessible to a much broader community.

Single-molecule localization microscopy (SMLM) breaks the optical diffraction limit by numerically localizing sparse fluorescence emitters to achieve super-resolution imaging. Spectroscopic SMLM or sSMLM further allows simultaneous spectroscopy and super-resolution imaging of fluorescence molecules. Hence, sSMLM can extract spectral features with single-molecule sensitivity, higher precision, and higher multiplexity than traditional multicolor microscopy modalities. These new capabilities enabled advanced multiplexed and functional cellular imaging applications. While sSMLM suffers from reduced spatial precision compared to conventional SMLM due to splitting photons to form spatial and spectral images, several methods have been reported to mitigate these weaknesses through innovative optical design and image processing techniques. This review summarizes the recent progress in sSMLM, its applications, and our perspective on future work., (© 2023. The Author(s).)

The study was conducted to figure out the function and mechanism of circular RNA circCAMSAP1 in repressing malignant behavior of endometrial carcinoma (EC) by targeting microRNA (miR)-370-3p /MAPK1. Tumor tissues and normal adjacent tissues of EC patients were harvested, and circCAMSAP1 and MAPK1 were elevated but miR-370-3p was reduced in tissues and cells of EC patients. Functional test results clarified transfection of si-circCAMSAP1 or miR-370-3p-mimic refrained cancer cell proliferation, migration and invasion, but motivated cancer cell apoptosis. Meanwhile, the amount of E-cadherin elevated and the amount of N-cadherin elevated or reduced. After co-transfection with si-circCAMSAP1 and miR-370-3p-inhibitor, miR-370-3p-inhibitor blocked si-circCAMSAP1's therapeutic impact. Furthermore, after co-transfection of pcDNA-circCAMSAP1 and si-MAPK1, si-MAPK1 turned around the malignant effect of pcDNA-circCAMSAP1. It was testified that miR-370-3p was circCAMSAP1's target, and inversely controlled via circCAMSAP1. Meanwhile, enhancing miR-370-3p led to repressive MAPK1, which was recognized as miR-370-3p's downstream target. All in all, the results of this study convey silencing circCAMSAP1 refrains the malignant behavior of EC by controlling miR-370-3p /MAPK1 axis.

Parkinson's disease (PD) is a neurodegenerative disease characterized by the pathological loss of nigrostriatal dopaminergic neurons, which causes an insufficient release of dopamine (DA) and then induces motor and nonmotor symptoms. Hyperoside (HYP) is a lignan component with anti-inflammatory, antioxidant, and neuroprotective effects. In this study, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its active neurotoxic metabolite 1-methyl-4-phenylpyridinium ion (MPP + ) were used to induce dopaminergic neurodegeneration. The results showed that HYP (100 µg/mL) reduced MPTP-mediated cytotoxicity of SH-SY5Y cells in vitro, and HYP [25 mg/(kg d)] alleviated MPTP-induced motor symptoms in vivo. HYP treatment reduced the contents of nitric oxide (NO), H 2 O 2 , and malondialdehyde (MDA), as well as the mitochondrial damage of dopaminergic neurons, both in vitro and in vivo. Meanwhile, HYP treatment elevated the levels of neurotrophic factors such as glial cell line-derived neurotrophic factor, brain-derived neurotrophic factor, and recombinant cerebral dopamine neurotrophic factor in vivo, but not in vitro. Finally, Akt signaling was activated after the administration of HYP in MPP + /MPTP-induced dopaminergic neurodegeneration. However, the blockage of the Akt pathway with Akt inhibitor did not abolish the neuroprotective effect of HYP on DA neurons. These results showed that HYP protected the dopaminergic neurons from the MPP + - and MPTP-induced injuries, which did not rely on the Akt pathway., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Spectroscopic single-molecule localization microscopy (sSMLM, or spectroscopic nanoscopy) has been established as a key tool in functional super-resolution imaging by providing spatial and spectral information of single molecules at nanoscale resolution. A recently developed dual-wedge prism (DWP) imaging spectrometer, a monolithic optical component, has broadened the accessibility of sSMLM with an improved imaging resolution of more than 40%. It also improved the system reliability by reducing the number of discrete optical components. However, achieving its optimal performance requires the comprehensive understanding of the underlying constraints of the key system parameters, such as the refractive index of the DWP, spectral dispersion (SD), axial separation for three-dimensional (3D) biplane reconstruction, and the overall dimensional constraints. In this work, we present a generalized design principle for the DWP imaging spectrometer. Specifically, we develop the theoretical framework capturing the influence of the primary design parameters, including the achievable SD and localization performance, for different design cases. It further establishes the workflow to design and optimize the DWP imaging spectrometer for better multi-color functional imaging. This will give practical guidance for users to easily design the DWP imaging spectrometer, allowing for straightforward 3D sSMLM implementation.

This study investigated the knowledge, thoughts, and attitudes of oncology nurses in China regarding fertility preservation for male cancer patients of childbearing age, and for offering counseling or oncofertility services for the men in their care. Data was collected from 18 oncology nurses in Southwest China through voluntary self-report and in-depth interviews. The qualitative interview data were analyzed using a descriptive phenomenology method based on the lived experience of the nurses. The interviewees commonly reported 6 main concerns regarding fertility preservation (FP): their insufficient knowledge and inadequate nursing education; the importance of offering such services to cancer patients; legal vulnerability if FP information is withheld from patients; the role of the nurse in counseling; and barriers to discussing FP in practice. Nurses had a positive attitude toward FP, but most had no practical role in routinely informing male patients of their options, and the nurses believed that discussion of FP was outside their scope of practice. This study offers insight into the perceptions of oncology nurses in a developing country regarding the provision of FP services for adult male cancer patients. These results lead us to recommend that local fertility nurses should be given new training regarding FP. Furthermore, nurse-led clinics are desirable. Future research should focus on the effectiveness of nurse participation in FP counseling and referral, and how to improve the professional confidence of oncology nurses for addressing FP issues., (© 2021. American Association for Cancer Education.)

Objective: The aim of the study is to investigate whether nano-calcium carbonate (nano-CaCO 3 ) occupational exposure could induce adverse health effects in workers., Methods: A cross-sectional study was conducted in a nano-CaCO 3 manufacturing plant in China. Then, we have studied the dynamic distribution of nano-CaCO 3 in nude mice and examined the oxidative damage biomarkers of subchronic administrated nano-CaCO 3 on Sprague-Dawley rats., Results: The forced vital capacity (%) and the ratio of FEV1 to FVC is the rate of one second of workers were significantly decreased than unexposed individuals. Dynamic imaging in mice of fluorescence labeled nano-CaCO 3 showed relatively high uptake and slow washout in lung. Similar to population data, the decline in serum glutathione level and elevation in serum MDA were observed in nano-CaCO 3 -infected Sprague-Dawley rats., Conclusions: We found that nano-CaCO 3 exposure may result in the poor pulmonary function in workers and lead to the changes of oxidative stress indexes., Competing Interests: Conflict of interests: None declared., (Copyright © 2022 American College of Occupational and Environmental Medicine.)

Based on the structures of natural products streptochlorin and pimprinine derived from marine or soil microorganisms, a series of streptochlorin derivatives containing the nitrile group were designed and synthesized through acylation and oxidative annulation. Evaluation for antifungal activity showed that compound 3a could be regarded as the most promising candidate-it demonstrated over 85% growth inhibition against Botrytis cinerea, Gibberella zeae, and Colletotrichum lagenarium , as well as a broad antifungal spectrum in primary screening at the concentration of 50 μg/mL. The SAR study revealed that non-substituent or alkyl substituent at the 2-position of oxazole ring were favorable for antifungal activity, while aryl and monosubstituted aryl were detrimental to activity. Molecular docking models indicated that 3a formed hydrogen bonds and hydrophobic interactions with Leucyl-tRNA Synthetase, offering a perspective for the possible mechanism of action for antifungal activity of the target compounds.

Conventional methods have relied on specialized imaging equipment and advanced fabrication process to solve the problem of accurately aligning a microsensor to an optical fiber which is critical for its detection efficiency. To dramatically lower the barrier to high-precision alignment, we present a technique much easier to implement and much lower in cost. By fabricating replicable alignment and proximity structures on the surface of the sensor chip, we can achieve accurate alignment and position the fiber tip very close to the sensor without damaging it. We introduce an easy setup to examine the alignment result and demonstrate accurate alignment of dummy sensors as small as 5μm×5μm. We use our alignment method to realize efficient input coupling for a superconducting transition-edge sensor as an example of fruitful adoption in many possible applications.

Objective: To investigate the protective effects and its possible mechanism of Wuzi Yanzong Pill (WYP) on Parkinson's disease (PD) model mice., Methods: Thirty-six C57BL/6 male mice were randomly assigned to 3 groups including normal, PD, and PD+WYP groups, 12 mice in each group. One week of intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to establish the classical PD model in mice. Meanwhile, mice in the PD+WYP group were administrated with 16 g/kg WYP, twice daily by gavage. After 14 days of administration, gait test, open field test and pole test were measured to evaluate the movement function. Tyrosine hydroxylase (TH) neurons in substantia nigra of midbrain and binding immunoglobulin heavy chain protein (GRP78) in striatum and cortex were observed by immunohistochemistry. The levels of TH, GRP78, p-PERK, p-eIF2α, ATF4, p-IRE1α, XBP1, ATF6, CHOP, ASK1, p-JNK, Caspase-12, -9 and -3 in brain were detected by Western blot., Results: Compared with the PD group, WYP treatment ameliorated gait balance ability in PD mice (P<0.05). Similarly, WYP increased the total distance and average speed (P<0.05 or P<0.01), reduced rest time and pole time (P<0.05). Moreover, WYP significantly increased TH positive cells (P<0.01). Immunofluorescence showed WYP attenuated the levels of GRP78 in striatum and cortex. Meanwhile, WYP treatment significantly decreased the protein expressions of GRP78, p-PERK, p-eIF2α, ATF4, p-IRE1 α, XBP1, CHOP, Caspase-12 and Caspase-9 (P<0.05 or P<0.01)., Conclusions: WYP ameliorated motor symptoms and pathological lesion of PD mice, which may be related to the regulation of unfolded protein response-mediated signaling pathway and inhibiting the endoplasmic reticulum stress-mediated neuronal apoptosis pathway., (© 2022. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

The lymphatic vascular system is crucial for the regulation of tissue fluid homeostasis, lipid metabolism, and immune function. Cardiac injury quickly leads to myocardial edema, cardiac lymphatic dysfunction, which ultimately results in myocardial fluid imbalance and cardiac dysfunction. Therefore, lymphangiogenesis-targeted therapy may improve the recovery of myocardial function post cardiac ischemia as observed in myocardial infarction (MI). Indeed, a promising strategy for the clinical treatment of MI relies on vascular endothelial growth factor-C (VEGF-C)-targeted therapy, which promotes lymphangiogenesis. However, much effort is needed to identify the mechanisms of lymphatic transport in response to heart disease. This article reviews regulatory factors of lymphangiogenesis, and discusses the effects of lymphangiogenesis on cardiac function after cardiac injury and its regulatory mechanisms. The involvement of stem cells on lymphangiogenesis was also discussed as stem cells could differentiate into lymphatic endothelial cells (LECs) and stimulate phenotype of LECs., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Resent study suggests that c-kit + cells in bone marrow-derived MSCs may differentiate toward cardiamyocytes. However, the properties of c-kit + MSCs remain unclear. This study isolated c-kit + VEGFR-2 + cells from rat bone marrow-derived MSCs, and assessed potential of c-kit + VEGFR-2 + MSCs to differentiate towards cardiovascular cells and their efficiency of repairing the infarcted myocardium after transplantation. Gene expression profile of the cells was analyzed with RNA-sequencing. Potential of differentiation of the cells was determined after induction. Rat models of myocardial infarction were established by ligation of the left anterior descending coronary artery. The cells were treated with hypoxia and serum deprivation for four hours before transplantation. Improvement of cardiac function and repair of the infarcted myocardium were assessed at four weeks after transplantation. Gene expression profile revealed that c-kit + VEGFR-2 + MSCs expressed most smooth muscle-specific and myocardium-specific genes, while expression of endothelium-specific genes was upregulated significantly. After induction with VEGF or TGF-β for two weeks, the cells expressed CD31 and α-SMA respectively. At three weeks, BMP-2-induced cells expressed cTnT. After transplantation of the cells, cardiac function was improved, scar size of the infarcted myocardium was decreased, and angiogenesis and myocardial regeneration were enhanced significantly. Moreover, paracrine in the myocardium was increased after transplantation. These results suggest that c-kit + VEGFR-2 + MSCs have a potential of differentiation towards cardiovascular cells. Transplantation of c-kit + VEGFR-2 + MSCs is effective for repair of the infarcted myocardium. c-kit + VEGFR-2 + MSCs may be a reliable source for cell therapy of ischaemic diseases., (© 2022. The Author(s).)

Objective: To establish the norms and clinical application standards of mass spectrometry method to measure vitamin D in capillary blood. Methods: Following the "Province-City-Hospital" sampling procedure, a cross-sectional sample of 1 655 healthy children under 7 years of age were recruited from 12 provinces, autonomous regions, or municipalities in China from November 2020 to December 2021. Both venous and capillary blood samples from the same individual were collected, for which serum 25(OH)D levels were measured by high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method. Pearson correlation analysis and linear regression analysis were used to detect the correlation and determine a correction algorithm. The agreement was analyzed using Bland-Altman plot and Kappa statistic. The sensitivity and specificity were evaluated using receiver operating characteristic (ROC) curve method. Results: Venous and capillary 25(OH)D levels of 1 655 healthy children under 7 years of age were 74.25 (59.50, 92.00) and 68.75 (54.44, 86.25) nmol/L, respectively, showed a significant difference( Z =22.14, P <0.001) as well as a highly significant correlation between venous and capillary 25(OH)D levels( r =0.95, P <0.001). Linear regression analysis was then performed to determine the correction algorithm: lg(corrected capillary 25(OH)D)=0.13+0.95×lg(capillary 25(OH)D)( R 2 =0.90, P <0.001). The deviation between venous and corrected capillary 25(OH)D levels was (0.50±17.50) nmol/L, a difference value that did not reach statistical significance ( P >0.05). The cut-off values of capillary blood 25(OH)D values 30.00, 50.00, 75.00 nmol/L corresponding to venous blood 25(OH)D values were 26.59, 45.56, and 69.84 nmol/L, respectively. Good consistency was observed between venous and corrected capillary 25(OH)D levels in clinical diagnosis (Kappa value 0.68-0.81). Corrected capillary 25(OH)D showed a high clinically predictive value (area under curve 0.97-0.99,sensitivity 0.72-0.92,specificity 0.89-0.99). Conclusion: The standardized capillary HPLC-MS/MS method can be used to detect 25(OH)D levels in children clinically.

A non-reciprocity sensor based on a layered structure with multitasking is proposed, which realizes biological detection and angle sensing. Through an asymmetrical arrangement of different dielectrics, the sensor obtains non-reciprocity on the forward and backward scales, thus achieving multi-scale sensing in different measurement ranges. The structure sets the analysis layer. Injecting the analyte into the analysis layers by locating the peak value of the photonic spin Hall effect (PSHE) displacement, cancer cells can accurately be distinguished from normal cells via refractive index (RI) detection on the forward scale. The measurement range is 1.569∼1.662, and the sensitivity (S) is 2.97 × 10 -2 m/RIU. On the backward scale, the sensor is able to detect glucose solution with 0∼400 g/L concentrations (RI = 1.3323∼1.38), with S = 1.16 × 10 -3 m/RIU. When the analysis layers are filled with air, high-precision angle sensing can be achieved in the terahertz range by locating the incident angle of the PSHE displacement peak; 30°∼45°, and 50°∼65° are the detection ranges, and the highest S can reach 0.032 THz/°. This sensor contributes to detecting cancer cells and biomedical blood glucose and offers a new way to the angle sensing.

Chrysanthemum morifolium is a well-known edible medicinal plant in Asia and some other regions. Content of selenium in Se-enriched C. morifolium (SeCM) is significantly higher than that in traditional C. morifolium (non-Se-enriched C. morifolium, TCM). In order to understand health effects of SeCM, its chemical composition, lifespan-prolonging activities, and impacts on antioxidant defense-related gene expressions of model organism D. melanogaster were systematically studied. A total of eight phenols, including luteolin-7-O-glucoside, linarin, luteolin, apigenin, diosmetin, acacetin, 3-caffeoylquinic acid and 4,5-dicaffeoylquinic acid, were identified in SeCM extract. Compared with TCM, SeCM exhibited superior antioxidant properties. Intake of SeCM dramatically reduced malondialdehyde level and increased activities of endogenous antioxidant enzymes in fruit flies. SeCM was able to upregulate gene expressions of Cu/Zn-superoxide dismutase, Mn-superoxide dismutase and hydrogen peroxide catalase, and extend lifespans of fruit flies. Comparatively high antioxidant capacities and lifespan-prolonging activities of SeCM might be attributed to its abundant phenols and selenium, which probably ameliorated accumulation of free radicals and susceptibility to oxidative stress. These findings provide clues on further exploitation and utilization of Se-enriched C. morifolium. PRACTICAL APPLICATIONS: Chrysanthemum morifolium has been used for nutraceutical and curative purposes in China for thousands of years. Se-enriched C. morifolium typically contains more selenium than traditional C. morifolium, and is widely consumed in Asia and some other regions. Selenium is an essential micronutrient for humans, and selenium deficiency may result in several diseases such as myocardial infarction. SeCM is one of important selenium supplements. In this study, SeCM was found to upregulate gene expressions of Cu/Zn-superoxide dismutase, Mn-superoxide dismutase, and hydrogen peroxide catalase, and extend lifespans of experimental animals. These results provide supporting information for developing SeCM-based functional foods with distinct health benefits., (© 2022 Wiley Periodicals LLC.)

Objective: The aim of this study was to analyze the epidemiological characteristics of the causes of chronic kidney disease (CKD) stage 5 patients in North China and to investigate the economic burden of those on hemodialysis (HD) or peritoneal dialysis (PD), as well as the associated influencing factors., Methods: General clinical information, etiological categories, and hospitalization costs for HD or PD were collected from 1,515 patients hospitalized with stage 5 CKD at the Affiliated Hospital of Hebei University from 2016 to 2018. Logistic regression analysis was used to analyze the independent influencing factors affecting patients' financial burden., Results: The highest rate of DN was found in patients aged 70 years or older (27.0%) and the highest incidence of primary glomerulopathy was found in patients aged <50 years (24.3%). Age, type of dialysis, and type of health insurance were independent influences on the total financial burden of patients, and the results of multifactorial logistic regression analysis showed that age [OR (95% CI): 1.009 (1.002, 1.020)] and type of dialysis [OR (95% CI): 1.746 (1.149, 2.659)] would increase the total financial burden. The type of health insurance would reduce the total financial burden [OR (95% CI): 0.222 (0.108, 0.418)]., Conclusion: Chronic kidney disease, with its complex etiology and the heavy financial burden required for treatment, remains a more serious public health problem globally, and it is therefore necessary to further improve medical coverage for dialysis patients, increase management efforts, broaden pro-poor policies and increase the accessibility of medical services in low- and middle-income areas., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Guo, Gou, Li, Zhang, Huang, Zheng, Chen and Sui.)

Chemically protected sodium butyrate (CSB) is a new kind of sodium butyrate. Our previous study found that 1,000 mg/kg of CSB had the potential capacity of improving growth performance and promoting early development of small intestine in broilers. This study aimed to investigate the effect of long-term antibiotics or CSB supplementation for intestinal microflora dynamical regulation in broilers. One hundred ninety-two 1-day-old Arbor Acres male broilers were randomly allocated into 3 dietary treatment (8 replicates per treatment) and fed with a basal diet (CON), a diet supplemented with the antibiotics (enramycin, 8 mg/kg and aureomycin, 100 mg/kg) (ANT), or a diet supplemented with 1,000 mg/kg of CSB, respectively. Results showed that dietary supplementation of CSB or ANT treatment elevated the weight gain and feed conversion ratio (FCR; P < 0.05), as compared with control (CON) group. Additionally, CON, CSB, or ANT administration dynamically altered the gut microbiota composition as time goes on. The increased presence of potential pathogens, such as Romboutsia and Shuttleworthia, and decreased beneficial bacteria such as Alistipes, Akkermansia, and Bacteroides were verified in new gut homeostasis reshaped by long-term antibiotics treatment, which has adverse effects on intestinal development and health of broilers. Conversely, CSB supplementation could dynamically enhance the relative abundance of Bacteroides, and decrease Romboutsia and Shuttleworthia in new microflora, which has positive effects on intestinal bacteria of broilers compared with CON group. Meanwhile, CSB supplementation was significantly increased the concentration of propionic acid and total short chain fatty acids (total SCFA; P < 0.05) in comparison with CON and ANT groups. Moreover, CSB treatment significantly increased anti-inflammatory and antioxidative capacities (P < 0.05) of broilers compared with ANT group. Taken together, we revealed characteristic structural changes of gut microbiota throughout long-term CSB or ANT supplementation in broilers, which provided a basic data for evaluating the mechanism of action affecting intestinal health by CSB or ANT administration and CSB as an alternative to antibiotics in the broilers industry., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Retinal ganglion cells (RGCs) are heterogeneous projection neurons that convey distinct visual features from the retina to brain. Here, we present a high-throughput in vivo RGC activity assay in response to light stimulation using noninvasive Ca 2+ imaging of thousands of RGCs simultaneously in living mice. Population and single-cell analyses of longitudinal RGC Ca 2+ imaging reveal distinct functional responses of RGCs and unprecedented individual RGC activity conversions during traumatic and glaucomatous degeneration. This study establishes a foundation for future in vivo RGC function classifications and longitudinal activity evaluations using more advanced imaging techniques and visual stimuli under normal, disease, and neural repair conditions. These analyses can be performed at both the population and single-cell levels using temporal and spatial information, which will be invaluable for understanding RGC pathophysiology and identifying functional biomarkers for diverse optic neuropathies.

Pimprinine and streptochlorin are indole alkaloids derived from marine or soil microorganisms. In our previous study, they were promising lead compounds due to their potent bioactivity in preventing many phytopathogens, but further structural modifications are required to improve their antifungal activity. In this study, pimprinine and streptochlorin were used as parent structures with the combination strategy of their structural features. Three series of target compounds were designed and synthesized. Subsequent evaluation for antifungal activity against six common phytopathogenic fungi showed that some of thee compounds possessed excellent effects, and this is highlighted by compounds 4a and 5a , displaying 99.9% growth inhibition against Gibberella zeae and Alternaria Leaf Spot under 50 μg/mL, respectively. EC 50 values indicated that compounds 4a , 5a , 8c, and 8d were even more active than Azoxystrobin and Boscalid. SAR analysis revealed the relationship between 5-(3'-indolyl)oxazole scaffold and antifungal activity, which provides useful insight into the development of new target molecules. Molecular docking models indicate that compound 4a binds with leucyl-tRNA synthetase in a similar mode as AN2690, offering a perspective on the mode of action for the study of its antifungal activity. These results suggest that compounds 4a and 5a could be regarded as novel and promising antifungal agents against phytopathogens due to their valuable potency., Competing Interests: The authors declare no conflicts of interest.

Background: C1q/TNF-related protein 9 (CTRP9) and adiponectin (APN) have beneficial metabolic regulatory and vasoprotective effects. This study explored alteration of CTRP9 and APN multimers during onset of ischemic stroke and development, to provide novel clinical and experimental basis for recognition and prevention of ischemic stroke., Methods: There were 269 patients with ischemic stroke and 182 control subjects included in this study. Serum levels of CTRP9 and APN multimers in different disease stages were measured., Results: Serum CTRP9, total APN (tAPN), and high-molecular weight (HMW) APN decreased gradually in stage I (acute stage, within 72 h of onset) of ischemic stroke and increased during stage III (11th day to one month) and stage IV (1 month after), compared to control. In the non-hyperlipidemia group, serum CTRP9, tAPN, and HMW were decreased in ischemic stroke patients compared to control (P < 0.05). Serum CTRP9 is closely related to serum tAPN and HMW (r = 0.992, 0.991). Serum CTRP9 are protective against ischemic stroke (OR = 0.400, 95% CI 0.197-0.810, P < 0.05)., Conclusions: Lower serum CTRP9, tAPN, LMW, and HMW are significantly associated with increased ischemic stroke risk in non-hyperlipidemia subjects. CTRP9, tAPN, and HMW isoforms may be valuable clinical indicators for patients with ischemic stroke., (© 2022. The Author(s).)

Objective: Asthma is a chronic airway inflammatory disease caused by high infiltration of multiple inflammatory cells and factors in airway tissues. Statins may inhibit inflammation, hence improve asthma symptoms. This meta-analysis aimed to assess the efficacy of statins in the treatment of asthma patients., Materials and Methods: We searched in PubMed, OVID, Cochrane Library, and Web of Science databases using the following key words: "statin", "atorvastatin", "simvastatin", "pravastatin", "rosuvastatin", "pitavastatin", "fluvastatin", and "asthma". The effects of statins on function, serum biomarkers, sputum mediators, and serum biochemical markers were analyzed from the identified studies., Results: Twelve articles (613 participants) were included in the meta-analysis. Results showed that statins significantly improved asthma symptoms (ACQ score: MD: -0.43, 95% CI: -0.47 - -0.38, p<0.01; ACT score: MD: 1.96, 95% CI: 1.26-2.67, p<0.01). Furthermore, statins significantly reduced serum hsCRP (MD: -0.50, p=0.02) and cholesterol (MD: -32.76, p<0.01) levels and the proportion of sputum eosinophils (MD: -1.25, p<0.01) and IL6 levels (MD: -64.56, p=0.04) in sputum. However, lung function was not significantly different between the statin and placebo treatment groups., Conclusions: Although statins did not change the lung function in patients with asthma, they improved asthma symptoms and reduced the serum hsCRP, sputum eosinophil ratio, and IL6 levels.

The infiltration of polymorphonuclear leukocytes (PMNs) in ischemia-reperfusion injury (I/RI) has been implicated as a critical component of inflammatory damage following ischemic stroke. However, successful blockade of PMN transendothelial migration (TEM) in preclinical studies has not translated to meaningful clinical outcomes. To investigate this further, leukocyte infiltration patterns were quantified, and these patterns were modulated by blocking platelet endothelial cell adhesion molecule-1 (PECAM), a key regulator of TEM. LysM-eGFP mice and microscopy were used to visualize all myeloid leukocyte recruitment following ischemia/reperfusion. Visual examination showed heterogeneous leukocyte distribution across the infarct at both 24 and 72 hours after I/RI. A semiautomated process was designed to precisely map PMN position across brain sections. Treatment with PECAM function-blocking antibodies did not significantly affect total leukocyte recruitment but did alter their distribution, with more observed at the cortex at both early and later time points (24 hours: 89% PECAM blocked vs. 72% control; 72 hours: 69% PECAM blocked vs. 51% control). This correlated with a decrease in infarct volume. These findings suggest that TEM, in the setting of I/RI in the cerebrovasculature, occurs primarily at the cortical surface. The reduction of stroke size with PECAM blockade suggests that infiltrating PMNs may exacerbate I/RI and indicate the potential therapeutic benefit of regulating the timing and pattern of leukocyte infiltration after stroke., (Copyright © 2022 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Objective: BCOR gene, encoding a corepressor of BCL6, plays an important role in fetal development. BCOR mutations were previously associated with oculofaciocardiodental syndrome (OFCD or MCOPS2, OMIM# 300166). The BCOR protein is ubiquitously expressed in multiple areas, including the brain. However, the role of BCOR in neurological disorder remains elusive., Methods: Trios-based whole-exome sequencing was performed in a cohort of 323 cases with partial epilepsy without acquired causes., Results: Seven hemizygous missense BCOR variants, including c 0.103 G>C/p.Asp35His, c.1079 A>G/p.His360Arg, c 0.1097 C>T/p.Thr366Ile, c 0.3301 C>T/p.Pro1101Ser, c 0.3391 C>T/p.Arg1131Trp, c 0.4199 G>A/p.Arg1400Gln, and c 0.5254 G>A/p.Asp1752Asn, were identified in seven cases with partial epilepsy. Two patients presented partial seizures with generalized seizures and/or generalized discharges. One case showed cortical dysplasia in the right temporal-occipital area on MRI. Two cases presented mild developmental delay. However, all patients achieved seizure-free. The frequency of BCOR variants in the present cohort was significantly higher than that in the controls of healthy Chinese volunteers and all populations of Genome Aggregation Database (gnomAD). Computational modeling, including hydrogen bond and prediction of protein stability, implied that the variants lead to structural impairment. Previously, OFCD associated BCOR mutations were mostly destructive mutations in an X-linked dominant (XLD) pattern; in contrast, the BCOR variants identified in this study were all missense variants, which were associated with partial epilepsy in an X-linked recessive (XLR) pattern. The proportion of missense mutations in epilepsy was significantly higher than that in OFCD., Conclusions: BCOR was potentially a candidate pathogenic gene of partial epilepsy with or without developmental delay. The genotype-phenotype correlation helps understanding the mechanism underlying phenotypic variation., Competing Interests: Conflict of interests All authors claim that there are no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Vancomycin remains the mainstay of treatment for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. This study assessed risk factors for vancomycin failure in 63 patients with MRSA pneumonia through detailed clinical, microbiological, pharmacokinetic/pharmacodynamic, and genetic analyses of prospective multicenter studies conducted from February 2012 to July 2018. Therapeutic drug monitoring was performed during vancomycin treatment, and the 24-h area under the curve (AUC 0-24 ) was calculated. All baseline strains were collected for MIC determination, heterogeneous vancomycin-intermediate S. aureus (hVISA) screening, and biofilm determination. Whole-genome sequencing was performed on the isolates to analyze their molecular typing and virulence and adhesion genes. Clinical signs and symptoms improved in 44 patients (44/63, 69.8%), with vancomycin daily dose ( P =  0.045), peak concentration ( P =  0.020), and sdrC ( P =  0.047) being significant factors. Isolates were eradicated in 51 patients (51/63, 81.0%), with vancomycin daily dose ( P =  0.009), cardiovascular disease ( P =  0.043), sequence type 5 (ST5; P = 0.017), tst ( P =  0.050), and sec gene ( P =  0.044) associated with bacteriological failure. Although the AUC 0-24 /MIC was higher in the groups with bacterial eradication, the difference was not statistically significant ( P =  0.108). Multivariate analysis showed that no variables were associated with clinical efficacy; ST5 was a risk factor for bacterial persistence (adjusted odds ratio, 4.449; 95% confidence interval, 1.103 to 17.943; P =  0.036). ST5 strains had higher frequencies of the hVISA phenotype, biofilm expression, and presence of some adhesion and virulence genes such as fnbB , tst , and sec than non-ST5 strains. Our study suggests that ST5 is a possible predictor of bacterial persistence in MRSA pneumonia treated with vancomycin. IMPORTANCE Few studies have simultaneously examined the influence of clinical characteristics of patients with pneumonia, the vancomycin pharmacokinetic/pharmacodynamic (PK/PD) index, and the phenotypic and genetic characteristics of methicillin-resistant Staphylococcus aureus (MRSA) strains. We assessed risk factors for vancomycin failure in patients with MRSA pneumonia by analyzing these influences in a prospective multicenter study. Sequence type 5 (ST5) was a possible predictor of bacterial persistence in adult patients with MRSA pneumonia (adjusted odds ratio, 4.449). We found that this may be related to ST5 strains having higher levels of vancomycin heterogeneous resistance, biofilms, and the presence of adhesion and virulence genes such as fnbB , tst , and sec .

Super-resolution microscopy can capture spatiotemporal organizations of protein interactions with resolution down to 10 nm; however, the analyses of more than two proteins involving low-abundance protein are challenging because spectral crosstalk and heterogeneities of individual fluorescent labels result in molecular misidentification. Here we developed a deep learning-based imaging analysis method for spectroscopic single-molecule localization microscopy to minimize molecular misidentification in three-color super-resolution imaging. We characterized the 3-fold reduction of molecular misidentification in the new imaging method using pure samples of different photoswitchable fluorophores and visualized three distinct subcellular proteins in U2-OS cell lines. We further validated the protein counts and interactions of TOMM20, DRP1, and SUMO1 in a well-studied biological process, Staurosporine-induced apoptosis, by comparing the imaging results with Western-blot analyses of different subcellular portions.

Selenium polysaccharides (Se-polysaccharides) are one of important forms of organic Se, in which selenium (Se) and polysaccharides are joined by covalent bonds. In the present review, recent progress in chemical structure and hypoglycemic activity of Se-polysaccharides is summarized. In particular, the mechanism underlying hypoglycemic capacity of Se-polysaccharides is discussed, and the relationship between hypoglycemic activity and chemical structure is analyzed. Besides, strategies for further research into chemical structure and hypoglycemic activity of Se-polysaccharides are proposed. Hypoglycemic activity of Se-polysaccharides is closely related to their inhibitory effect on α-amylase and α-glucosidase, influence on insulin signal pathway especially IRS-PI3K-Akt signaling pathway, and protection capacity against oxidative stress., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Alsophila spinulosa, as a rare tree fern with potential medicinal value, has attracted extensive attention. Herein, the physicochemical properties, antioxidant and anti-aging activities of polysaccharide from A. spinulosa leaf (ALP) were investigated. ALP was composed of galactose, arabinose, glucose, rhamnose, galacturonic acid, mannose, and fucose. (1→), (1→6), and (1→2) bond types were the primary glycosidic bond in ALP. Surprisingly, ALP displayed the wonderful activity of antioxidant and anti-aging, including excellent scavenging ability against DPPH and ABTS radicals in vitro; prolonging the life span, improving activity of antioxidative enzymes (SOD and CAT), and decreasing the level of ROS, MDA in Caenorhabditis elegans. Meanwhile, ALP promoted DAF-16 to move into the nuclear. Overall, our results illustrated that ALP could be further developed as a functional food ingredient., (© 2022 Wiley-VHCA AG, Zurich, Switzerland.)

Anterior segment optical coherence tomography (AS-OCT) is a rapidly evolving area of OCT imaging, providing high-resolution and non-invasive volumetric imaging of the anterior segment. This review focuses on recent advances in AS-OCT imaging in small animals, which we categorize into ultrahigh-resolution, spectroscopic, magnetomotive, polarization-sensitive, and angiographic AS-OCTs. We summarize their technical foundations, review their applications to small animal imaging, and briefly discuss their current and future clinical applications., Competing Interests: Declaration of competing interest Hao F. Zhang has financial interests in Opticent Health, which did not support this work. Other authors declare no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The equations of state (EOS) of Iridium are, for the first time, obtained by solving the high-dimension integral of partition function based on a recently developed approach of ultrahigh efficiency and precision without any artificial parameter, and the deviation of 0.25% and 1.52% from the experiments was achieved respectively for the isobaric EOS in a temperature range of 300 K-2500 K and the isothermal EOS at 300 K up to 300 GPa. Specific comparisons show that the deviation of EOS based on harmonic approximation even including anharmonic effect, manifests worse than ours by several times or even one order of magnitude, indicating that ensemble theory is the very approach to understand the thermodynamic properties of condensed matter., (© 2022 IOP Publishing Ltd.)