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Arterial stiffness has been proved to be an important parameter in the evaluation of cardiovascular diseases, and Pulse Wave Velocity (PWV) is a strong indicator of arterial stiffness. Compared to regional PWV (PWV among different arteries), local PWV (PWV within a single artery) outstands in providing higher precision in indicating arterial properties, as regional PWVs are highly affected by multiple parameters, e.g., variations in blood vessel lengths due to individual differences, and multiple reflection effects on the pulse waveform. However, local PWV is less-developed due to its high dependency on the temporal resolution in synchronized signals with usually low signal-to-noise ratios. This paper presents a method for the noninvasive simultaneous measurement of two local PWVs in both left and right radial arteries based on the Fiber Bragg Grating (FBG) technique via correlation analysis of the pulse pairs at the fossa cubitalis and at the wrist. Based on the measurements of five male volunteers at the ages of 19 to 21 years old, the average left radial PWV ranged from 9.44 m/s to 12.35 m/s and the average right radial PWV ranged from 11.50 m/s to 14.83 m/s. What is worth mentioning is that a stable difference between the left and right radial PWVs was observed for each volunteer, ranging from 2.27 m/s to 3.04 m/s. This method enables the dynamic analysis of local PWVs and analysis of their features among different arteries, which will benefit the diagnosis of early-stage arterial stiffening and may bring more insights into the diagnosis of cardiovascular diseases.

IntroductionUndernutrition spontaneously occurs in ewes during late gestation and the pituitary is an important hinge in the neurohumoral regulatory system. However, little is known about the effect of undernutrition on pituitary metabolism.MethodsHere, 10 multiparous ewes were restricted to a 30% feeding level during late gestation to establish an undernutrition model while another 10 ewes were fed normally as controls. All the ewes were sacrificed, and pituitary samples were collected to perform transcriptome, metabolome, and quantitative real-time PCR analysis and investigate the metabolic changes.ResultsPCA and PLS-DA of total genes showed that undernutrition changed the total transcriptome profile of the pituitary gland, and 581 differentially expressed genes (DEGs) were identified between the two groups. Clusters of orthologous groups for eukaryotic complete genomes demonstrated that substance transport and metabolism, including lipids, carbohydrates, and amino acids, energy production and conversion, ribosomal structure and biogenesis, and the cytoskeleton were enriched by DEGs. Kyoto encyclopedia of genes and genomes pathway enrichment analysis displayed that the phagosome, intestinal immune network, and oxidative phosphorylation were enriched by DEGs. Further analysis found that undernutrition enhanced the lipid degradation and amino acid transport, repressing lipid synthesis and transport and amino acid degradation of the pituitary gland. Moreover, the general metabolic profiles and metabolic pathways were affected by undernutrition, repressing the 60S, 40S, 28S, and 39S subunits of the ribosomal structure for translation and myosin and actin synthesis for cytoskeleton. Undernutrition was found also to be implicated in the suppression of oxidative phosphorylation for energy production and conversion into a downregulation of genes related to T cell function and the immune response and an upregulation of genes involved in inflammatory reactions enriching phagosomes.DiscussionThis study comprehensively analyses the effect of undernutrition on the pituitary gland in a pregnant sheep model, which provides a foundation for further research into the mechanisms of undernutrition-caused hormone secretion and metabolic disorders.

Potassium niobate (KNbO3, KNO) has been intensively investigated for photovoltaic performance because of its non-toxicity and excellent nonlinear optical properties. The corresponding photovoltaic current density, however, remains very low due to a wide bandgap. Chemical doping and strain engineering strategies have been employed to tailor the band structure to enhance photovoltaic current density. Nevertheless, the original current density is still at a level of several tens of nA/cm2, significantly limiting device applications. In this work, we report a lattice-gradient KNO film on (100) single-crystal 0.7 wt. % Nb doped SrTiO3 (NSTO) substrate processed by annealing, generating a polarization-gradient that allows us to generate a large current density via a built-in field. The film exhibits a remarkable short-circuit current density (Jsc) of 58.63 µA/cm2 under the 375 nm irradiation of 500 mW/cm2 light intensity, where the corresponding responsivity (117.26 µA/W) is ∼3.82 times higher than those of reported KNO-based materials. It was revealed that the annealing process driven interfacial structure evolution from disorder to atomic-scale smoothness, accompanied by the transformation of the polarization shielding mechanism. After this process, an intriguing lattice-gradient throughout the film was established to have a uniform polarization direction, possibly accounting for the improved photovoltaic current density of KNO film. These findings may trigger interest in developing KNO as a potential key material for lead-free optoelectronic or photodetector devices.

Objectives: To analyze the epidemiologic features, culture positivity, the fungal spectrum of different sites of ocular infection in North China over 20 years from 2001 to 2020. Methods: 11, 635 patients suspected of ocular fungal infection were reviewed. The demographic profile, fungal positive culture rate among different sites, the distribution, and trends of main pathogens among cornea and intraocular fluid were analyzed. Results: Among 11, 635 samples, the positive culture rate of ocular fungal infection was 23.6%. Most of samples (83.1%) were from cornea, and their culture positivity was 26.9%. Fungal keratitis occurred more often during the harvesting season (October to December; 34.0%) than in other seasons (average: 22.0%). Fusarium sp. (53.2%), Aspergillus sp. (15.9%) and Alternaria sp. (12.5%) were the most common fungal species of ocular mycotic infections in the past two decades in north China. 2562 organisms were identified from cornea, of which 1443 (56.3%) were Fusarium sp., 403 (15.7%) and 329 (12.8%) were Aspergillus sp., and Alternaria sp., respectively. Of the 120 fungi isolated from the intraocular fluid, the most common was Aspergillus sp. (33.3%), followed by Fusarium sp. (24.2%) and Candida sp. (15.0%). Conclusions: Fusarium sp., Aspergillus sp. and Alternaria sp. were the most common organisms in cases of fungal keratitis, while Aspergillus sp., Fusarium sp. and Candida sp. were the most frequent isolates for fungal endophthalmitis.

Small Tail Han (STH) sheep, a unique Chinese breed, is recognized for its early maturity, year-round estrus, and prolificacy. However, the molecular mechanism of its high prolificacy has not been fully elucidated. The Proteomics approach is feasible and effective to reveal the proteins involved in the complex physiological processes of any organism. Given this, we performed the protein expression profiling of ovarian tissues during the luteal phase using polytocous STH sheep (litter size ≥2, three consecutive lambings) and monotocous STH sheep (litter size =1, three consecutive lambings) (PL vs. ML), and the follicular phase using polytocous STH sheep (litter size ≥2, three consecutive lambings) and monotocous STH sheep (litter size =1, three consecutive lambings) (PF vs. MF), respectively. Parallel Reaction Monitoring (PRM) was conducted to validate the differentially abundant proteins (DAPs). The tandem mass tag (TMT) quantitative proteomic results showed that a total of 5,237 proteins were identified, of which 49 and 44 showed differential abundance in the PL vs. ML and PF vs. MF groups, respectively. Enrichments analyses indicated that the DAPs including TIA1 cytotoxic granule-associated RNA-binding protein-like 1 (TIAL1), nicotinamide phosphoribosyltransferase (NAMPT), and cellular retinoic acid-binding protein 1 (CRABP1) were enriched at the luteal phase, while TIAL1, inhibin beta-a-subunit (A2ICA4), and W5PG55 were enriched at the follicular phase, potentially mediating reproductive processes in polytocous ewes. Furthermore, six DAPs were verified using PRM, confirming the accuracy of the TMT data acquired in this study. Together, our work expanded the database of indigenous sheep breeds and provided new ovarian candidate molecular targets, which will help in the study of the genetic mechanisms of ovine prolificacy.

Defects of solar panels can easily cause electrical accidents. The YOLO v5 algorithm is improved to make up for the low detection efficiency of the traditional defect detection methods. Firstly, it is improved on the basis of coordinate attention to obtain a LCA attention mechanism with a larger target range, which can enhance the sensing range of target features in addition to fully capturing feature information; secondly, the weighted bidirectional feature pyramid is used to balance the feature information with excessive pixel differences by assigning different weights, which is more conducive to multi-scale Fast fusion of features; finally, the usual coupled head of YOLO series is replaced with decoupled head, so that the task branch can be performed more accurately and the detection accuracy can be improved. The results of comparative experiments on the solar panel defect detection data set show that after the improvement of the algorithm, the overall precision is increased by 1.5%, the recall rate is increased by 2.4%, and the mAP is up to 95.5%, which is 2.5% higher than that before the improvement. It can more accurately determine whether there are defects, standardize the quality of solar panels, and ensure electrical safety.

Telomerase determines cell lifespan by controlling chromosome stability and cell viability, m6A epigenetic modification plays an important role in the regulation of telomerase activity. Using CRISPR epigenome editing to analyze specific m6A modification sites in telomerase will provide an important tool for analyzing the molecular mechanism of m6A modification regulating telomerase activity. In this review, we clarified the relevant applications of CRISPR system, paid special attention to the regulation of m6A modification in stem cells and cancer cells based on CRISPR system, emphasized the regulation of m6A modification on telomerase activity, pointed out that m6A modification sites regulate telomerase activity, and discussed strategies based on telomerase activity and disease treatment, which are helpful to promote the research of anti-aging and tumor related diseases.

IntroductionManganese (Mn) is an essential trace element for livestock, but little is known about the optimal Mn source and level for yak.MethodsTo improve yak’s feeding standards, a 48-h in vitro study was designed to examine the effect of supplementary Mn sources including Mn sulfate (MnSO4), Mn chloride (MnCl2), and Mn methionine (Met-Mn) at five Mn levels, namely 35 mg/kg, 40 mg/kg, 50 mg/kg, 60 mg/kg, and 70 mg/kg dry matter (includes Mn in substrates), on yak’s rumen fermentation.ResultsResults showed that Met-Mn groups showed higher acetate (p < 0.05), propionate, total volatile fatty acids (p < 0.05) levels, ammonia nitrogen concentration (p < 0.05), dry matter digestibility (DMD), and amylase activities (p < 0.05) compared to MnSO4 and MnCl2 groups. DMD (p < 0.05), amylase activities, and trypsin activities (p < 0.05) all increased firstly and then decreased with the increase of Mn level and reached high values at 40–50 mg/kg Mn levels. Cellulase activities showed high values (p < 0.05) at 50–70 mg/kg Mn levels. Microbial protein contents (p < 0.05) and lipase activities of Mn-Met groups were higher than those of MnSO4 and MnCl2 groups at 40–50 mg/kg Mn levels.DiscussionTherefore, Mn-met was the best Mn source, and 40 to 50 mg/kg was the best Mn level for rumen fermentation of yaks.

Mycoplasma ovipneumoniae (M. ovipneumoniae) causes a fatal infection in goats, leading to significant economic losses in the small-ruminant industry worldwide. The present study aimed to characterize the strains of M. ovipneumoniae infecting goats with pneumonia in Anhui Province, China. From November 2021 to January 2023, among 20 flocks, a total of 1320 samples (600 samples of unvaccinated blood, 400 nasal swabs, 200 samples of pleural fluid, and 120 samples of lung tissue) were obtained from goats with typical signs of pneumonia, such as a low growth rate, appetite suppression, increased temperature, discharge from the nose, and a cough. Necropsied goats showed increased pleural fluid, fibrinous pleuropneumonia, and attached localized pleural adhesions. M. ovipneumoniae isolated from the samples were subjected to an indirect hemagglutination test (IHA), PCR amplicon sequencing, phylogenetic analysis, and biochemical identification tests. The overall positivity rate of M. ovipneumoniae was 27.50%. Mycoplasmas were obtained from 80 (20.0%) nasal swabs, 21 (10.5%) pleural fluid samples, and 15 (12.5%) lung samples. PCR amplicon (288 bp) sequencing identified eight strains of M. ovipneumoniae. In a phylogenetic tree, the isolated strains were homologous to the standard strain M. ovipneumoniae Y-98 and most similar to M. ovipneumoniae FJ-SM. Local strains of M. ovipneumoniae were isolated from goats in Anhui province. The identified genomic features and population structure will promote further study of M. ovipneumoniae pathogenesis and could form the basis for vaccine and therapy development.

The aim of this study was to investigate the effects of sodium salicylate (SS) on the preservation and metabolic regulation of sheep sperm. Under 4 °C low-temperature conditions, SS (at 10 µM, 20 µM, 30 µM, and 50 µM) was added to the semen diluent to detect sperm motility, plasma membrane, and acrosome integrity. Based on the selected optimal concentration of SS (20 µM), the effects of 20 µM of SS on sperms’ antioxidant capacity and mitochondrial membrane potential (MMP) were evaluated, and metabolomics analysis was conducted. The results showed that on the 20th day of low-temperature storage, the sperm motility of the 20 µM SS group was 62.80%, and the activities of catalase (CAT) and superoxide dismutase (SOD) were significantly higher than those of the control group (p < 0.01). The content of Ca2+, reactive oxygen species (ROS), and malondialdehyde (MDA) were significantly lower than those of the control group (p < 0.01), and the total antioxidant capacity (T-AOC) was significantly higher than that of the control group (p < 0.05); mitochondrial activity and the total cholesterol (TC) content were significantly higher than those in the control group (p < 0.01). An ultrastructural examination showed that in the SS group, the sperm plasma membrane and acrosome were intact, the fibrous sheath and axoneme morphology of the outer dense fibers were normal, and the mitochondria were arranged neatly. In the control group, there was significant swelling of the sperm plasma membrane, rupture of the acrosome, and vacuolization of mitochondria. Using metabolomics analysis, 20 of the most significant differential metabolic markers were screened, mainly involving 6 metabolic pathways, with the amino acid biosynthesis pathway being the most abundant. In summary, 20 µM of SS significantly improved the preservation quality of sheep sperm under low-temperature conditions of 4 °C.

The study investigated the modification mechanism of modified ground calcium carbonate (GCC) mineral powder using in asphalt concrete. Two types of Titanate coupling agents, namely, K38S (TCA-K38S) and 201 (TCA-201), as well as sodium stearate coupling agent, were adopted to prepare modified GCC. The optimized preparation process was obtained through the orthogonal test. Two kinds of modified GCC were preferably selected to prepare asphalt concrete according to modification mechanism characterization, their performance was analyzed and evaluated at macro and micro levels. The study results show that, the optimal scheme of sodium stearate modified GCC is modification temperature of 80°C, modification time of 50 min, modifying agent dosage of 2.0%. The crystal structure of GCC remains unchanged after modification, with the original lattice structure being maintained. TCA-201 and sodium stearate exhibit better coating properties than that of TCA-K38S. The contact angles of TCA-201 and sodium stearate modified GCC are larger than that of TCA-K38S modified GCC. The in-service performance of AC-13C asphalt concrete modified with sodium stearate is found to be superior to that of TCA-201 modified AC-13C asphalt concrete. Compared with the unmodified AC-13C asphalt concrete, the Marshall modulus, residual stability, freeze-thaw splitting strength ratio, and maximum flexural tensile strain of sodium stearate modified AC-13C asphalt concrete are increased by 54.55%, 2.73%, 10.47%, and 26.41% respectively. This paper provides theoretical guidance for the application of GCC mineral powder in asphalt concrete.

Abstract Obesity induced by antipsychotics have plagued more than 20 million people worldwide. However, no drug is available to eliminate the obesity induced by antipsychotics. Here we examined the effect and potential mechanisms of a gold nanoclusters (AuNCs) modified by N-isobutyryl-L-cysteine on the obesity induced by olanzapine, the most prescribed but obesogenic antipsychotics, in a rat model. Our results showed that AuNCs completely prevented and reversed the obesity induced by olanzapine and improved glucose metabolism profile in rats. Further mechanism investigations revealed that AuNCs exert its anti-obesity function through inhibition of olanzapine-induced dysfunction of histamine H1 receptor and proopiomelanocortin signaling therefore reducing hyperphagia, and reversing olanzapine-induced inhibition of uncoupling-protein-1 signaling which increases thermogenesis. Together with AuNCs’ good biocompatibility, these findings not only provide AuNCs as a promising nanodrug candidate for treating obesity induced by antipsychotics, but also open an avenue for the potential application of AuNCs-based nanodrugs in treating general obesity.

Mentha haplocalyx Briq (MHB) and its components have been proven to improve the growth performance of livestock and poultry. The aim of this experiment was to investigate the effects of MHB addition on growth performance, rumen and fecal microbiota, rumen fluid, serum and urine metabolism, and transcriptomics of rumen epithelial cells in meat sheep. Twelve Hu sheep were selected for the experiment and fed with basic diet (CON) and a basal diet supplemented with 80 g/kg DM of Mentha haplocalyx Briq (MHB). The experimental period was 10 weeks with the first 2 weeks as the pre-trial period. The results showed that compared with the CON group, the average daily weight gain of meat sheep in the MHB group increased by 20.1%; the total volatile fatty acid (VFA) concentration significantly increased (p < 0.05); The thickness of the cecal mucosal layer was significantly reduced (p < 0.01), while the thickness of the colonic mucosal layer was significantly increased (p < 0.05), the length of ileal villi significantly increased (p < 0.01), the thickness of colonic mucosal layer and rectal mucosal muscle layer significantly increased (p < 0.05), and the thickness of cecal mucosal layer significantly decreased (p < 0.05); The serum antioxidant capacity has increased. At the genus level, the addition of MHB changed the composition of rumen and fecal microbiota, increased the relative abundance of Paraprevotella, Alloprevotella, Marinilabilia, Saccharibacteria_genera_incertae_sedis, Subdivision5_genera_incertae_sedis and Ornatilinea in rumen microbiota, and decreased the relative abundance of Blautia (p < 0.05). The relative abundance of Prevotella, Clostridium XlVb and Parasutterella increased in fecal microbiota, while the relative abundance of Blautia and Coprococcus decreased (p < 0.05). There were significant differences in the concentrations of 105, 163, and 54 metabolites in the rumen, serum, and urine between the MHB group and the CON group (p < 0.05). The main metabolic pathways of the differences were pyrimidine metabolism, taurine and taurine metabolism, glyceride metabolism, and pentose phosphate pathway (p < 0.05), which had a significant impact on protein synthesis and energy metabolism. The transcriptome sequencing results showed that differentially expressed genes were mainly enriched in immune regulation, energy metabolism, and protein modification. Therefore, adding MHB improved the growth performance of lambs by altering rumen and intestinal microbiota, rumen, serum and urine metabolomics, and transcriptome.

To improve the global optimization ability and convergence speed of the swarm intelligence algorithm, we proposed a new swarm intelligence optimization algorithm, namely the Oryctolagus cuniculus algorithm. This includes five mechanisms: the determination of safety zones, the cave escape, the agglomeration of Oryctolagus cuniculi, the maintenance of the Oryctolagus cuniculus king, and the zone competition. Each solution is represented by each Oryctolagus cuniculus’s position (including zone number and specific location number). The grass density and safety index at the location of the Oryctolagus cuniculus represents its fitness value. The determination of safety zones implies that predators such as eagles hunt Oryctolagus cuniculi in dangerous zones, and the zone without predators is considered a safety zone. The cave escape refers to the act of Oryctolagus cuniculi using a connected cave system to flee from a dangerous zone and reach a secure zone, thereby evading potential predators. We select the Oryctolagus cuniculus with higher fitness values as the king of each zone, and the Oryctolagus cuniculi gather towards the Oryctolagus cuniculus king. This mechanism ensures that Oryctolagus cuniculus mainly searches in zones with abundant grass and quickly finds the optimal solution. In the maintenance of the Oryctolagus cuniculus king, we choose the one with higher fitness values as the Oryctolagus cuniculus king. Zone competition is induced by an increase in the number of Oryctolagus cuniculi in zones with abundant grass by ordering the fitness values of each zone, and vice versa. We apply the Oryctolagus cuniculus algorithm to the inversion method of the asteroid spectra reflectance template. The experimental results show that compared with artificial rabbit optimization, this algorithm has a faster rate of convergence and better solution, effectively screens the reflectance template, and improves the Doppler difference velocimetry accuracy. In addition, the application of the Oryctolagus cuniculus algorithm to the knapsack problem also performs effectively.

To solve the problem of the non-linear Fourier phase shift caused by the wavelength shift in the celestial spectrum velocimetry, a celestial spectrum velocimetry method based on non-uniform discrete Fourier transform and compressed sensing is proposed. First, according to the properties of the non-uniform discrete Fourier transform with non-periodic celestial spectra, the non-linear relationship between the spectral wavelength shift and the Fourier phase shift is deduced theoretically. And then, the discrete cosine transform is used to decompose and reconstruct the spectrum to construct the phase dictionary of the non-periodic spectrum. In this dictionary, the spectral wavelength shift has a non-linear relationship with the Fourier phase shift. Finally, the non-uniform Fourier transform matrix is used as the measurement matrix. And the Doppler wavelength shift is estimated by using a non-linear and super-resolution matching algorithm to estimate the velocimetry. Experimental results show that when the spacecraft’s velocity is high, the celestial spectrum velocimetry method with non-linear Fourier phase shift (CSV-NFPS) can effectively measure the velocity from the spectrum, and its accuracy approaches the theoretical Cramer-Rao lower bounds (CRLB). Compared with the traditional Taylor method, the CSV-NFPS has an average accuracy improvement of 16.18% and a computational complexity reduction of 25.07%. In short, our method eliminate the non-linear bias in the celestial spectrum velocimetry and reduce a certain computational complexity.

Summary: Assays detecting blood transcriptome changes are studied for infectious disease diagnosis. Blood-based RNA alternative splicing (AS) events, which have not been well characterized in pathogen infection, have potential normalization and assay platform stability advantages over gene expression for diagnosis. Here, we present a computational framework for developing AS diagnostic biomarkers. Leveraging a large prospective cohort of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and whole-blood RNA sequencing (RNA-seq) data, we identify a major functional AS program switch upon viral infection. Using an independent cohort, we demonstrate the improved accuracy of AS biomarkers for SARS-CoV-2 diagnosis compared with six reported transcriptome signatures. We then optimize a subset of AS-based biomarkers to develop microfluidic PCR diagnostic assays. This assay achieves nearly perfect test accuracy (61/62 = 98.4%) using a naive principal component classifier, significantly more accurate than a gene expression PCR assay in the same cohort. Therefore, our RNA splicing computational framework enables a promising avenue for host-response diagnosis of infection. Motivation: Host-based response assays (HRAs) can often diagnose infectious disease earlier and more precisely than pathogen-based tests. However, the role of RNA alternative splicing (AS) in HRAs remains unexplored, as existing HRAs are restricted to gene expression signatures. We report a computational framework for the identification, optimization, and evaluation of blood AS-based diagnostic assay development for infectious disease. Using SARS-CoV-2 infection as a case study, we demonstrate the improved accuracy of AS biomarkers for COVID-19 diagnosis when compared against six reported transcriptome signatures and when implemented as a microfluidic PCR diagnostic assay.

Summary: Background: Fungal keratitis (FK) is a leading cause of corneal blindness in developing countries due to poor clinical recognition and laboratory identification. Here, we aimed to identify the distinct clinical signature of FK and develop a diagnostic model to differentiate FK from other types of infectious keratitis. Methods: We reviewed the electronic health records (EHRs) of all patients with suspected infectious keratitis in Beijing Tongren Hospital from January 2011 to December 2021. Twelve clinical signs of slit-lamp images were assessed by Lasso regression analysis and collinear variables were excluded. Three models based on binary logistic regression, random forest classification, and decision tree classification were trained for FK diagnosis and employed for internal validation. Independent external validation of the models was performed in a cohort of 420 patients from seven different ophthalmic centers to evaluate the accuracy, specificity, and sensitivity in real world. Findings: Three diagnostic models of FK based on binary logistic regression, random forest classification, and decision tree classification were established and internal validation were achieved with the mean AUC of 0.916, 0.920, and 0.859, respectively. The models were well-calibrated by external validation using a prospective cohort including 210 FK and 210 non-FK patients from seven eye centers across China. The diagnostic model with the binary logistic regression algorithm classified the external validation dataset with a sensitivity of 0.907 (0.774, 1.000), specificity 0.899 (0.750, 1.000), accuracy 0.905 (0.805, 1.000), and AUC 0.903 (0.808, 0.998). Interpretation: Our model enables rapid identification of FK, which will help ophthalmologists to establish a preliminary diagnosis and to improve the diagnostic accuracy in clinic. Funding: The Open Research Fund from the National Key Research and Development Program of China (2021YFC2301000) and the Open Research Fund from Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beijing Tongren Hospital, Beihang University & Capital Medical University (BHTR-KFJJ-202001) supported this study.

Abstract This paper studies the power production optimization problem of multiple offshore wind farms (OWFs) considering different maintenance demands and requirements under the wind power uncertainty. A decentralized robust operation optimization model is developed, in which OWFs and a maintenance service provider (MSP) are treated as individual stakeholders with different interests but coupled by maintenance resources. Based on the analytical target cascading (ATC) algorithm, the model is decoupled into independent models for MSP and each OWF. The operation and objectives of individual entities can be autonomously optimized only considering their own conditions. For each OWF, the power production planning coupled with maintenance scheduling is formulated as a two‐stage robust optimization model and solved by a column‐and‐constraint generation (C&CG) algorithm to tackle the wind power uncertainty. Numerical experiments demonstrate the effectiveness of the proposed model and the applicability of the integrated solution method to the studied problem. Results illustrate that the developed model shows a better guarantee for individual interests of OWFs, lower communication burden, and better information privacy than the centralized optimization model, especially in large‐scale systems. The integrated solution framework can guarantee a quick convergence and optimality. Moreover, it reduces impacts of uncertain factors on power productions and maintenance schemes.

Abstract Background There is an obvious correlation between ulcerative colitis and colorectal cancer, and the risk of colorectal cancer in patients with ulcerative colitis is increasing. Therefore, the combination therapy of anti-inflammatory and anti-tumor drugs may show promising to inhibit colon cancer. 5-aminosalicylic acid (5-ASA) with anti-inflammatory function is effective for maintaining remission in patients with ulcerative colitis and may also reduce colorectal cancer risk. Histone deacetylase (HDAC) plays an essential role in the progression of colon cancer. Butyric acid (BA) is a kind of HDAC inhibitor and thus shows tumor suppression to colon cancer. However, the volatile and corrosive nature of BA presents challenges in practical application. In addition, its clinical application is limited due to its non-targeting ability and low bioavailability. We aimed to synthesize a novel dual-prodrug of 5-ASA and BA, referred as BBA, to synergistically inhibit colon cancer. Further, based on the fact that folate receptor (FR) is over-expressed in most solid tumors and it has been identified to be a cancer stem cell surface marker in colon cancer, we took folate as the targeting ligand and used carboxymethyl-β-cyclodextrin (CM-β-CD) to carry BBA and thus prepared a novel inclusion complex of BBA/FA-PEG-CM-β-CD. Results It was found that BBA/FA-PEG-CM-β-CD showed significant inhibition in cell proliferation against colon cancer cells SW620. It showed a pro-longed in vivo circulation and mainly accumulated in tumor tissue. More importantly, BBA/FA-PEG-CM-β-CD gave great tumor suppression effect against nude mice bearing SW620 xenografts. Conclusions Therefore, BBA/FA-PEG-CM-β-CD may have clinical potential in colon cancer therapy. Graphical Abstract

Category: Ankle; Other Introduction/Purpose: Periprosthetic joint infection (PJI) is a devastating complication of arthroplasty. The well known PJI risk factors are useful for identifying high-risk patients but would be even more helpful for clinical decision-making if they are converted to a risk assessment scores. The Mayo Prosthetic Joint Infection Risk Score was based on the data of total hip and knee arthroplasty and has not been validated for application for total ankle arthroplasty. Methods: A series of 398 consecutive cases of total ankle arthroplasty, with minimal follow-up of 6 months, was reviewed for Mayo Periprosthetic Joint Infection Risk Score (Mayo score) and PJI. The patients' Mayo scores and PJI was examined by logistic regression. T-test was performed to compare the Mayo score between the non-infected TAA cases and infected cases. Receiver Operating Characteristic (ROC) was used to identify the critical value of Mayo score for total ankle arthroplasty. Results: There were 12 cases of PJI or 3.0% in the series. Of the 398 patients, the Mayo scores were in the range from -4 to 13 (median 2; interquartile range (IQR) 0-4). Preliminary analysis showed that, by logistic regression, the probability of PJI was increased as increases of the Mayo scores (Fig A). The mean Mayo score of the PJI patients (8.6+-1.8) was significantly greater than the rest of the patients (mean Mayo score 1.9+-3.4; p < .0001). ROC analysis showed that, when a Mayo score was greater than 5, the patient has a high probability of PJI (sensitivity = 100%; specificity = 86.9%; Fig B). Conclusion: This study showed a high correlation between the Mayo score and PJI in total ankle arthroplasty, which is the same trend as in total knee and hip arthroplasty. The preliminary results suggest that strategically focusing on the patients, who have a Mayo score > 5, could be a more efficient approach to prevent PJI after total ankle arthroplasty.

Background: Infectious keratitis (IK) is an ocular emergency caused by a variety of microorganisms, including bacteria, fungi, viruses, and parasites. Culture-based methods were the gold standard for diagnosing IK, but difficult biopsy, delaying report, and low positive rate limited their clinical application. Objectives: This study aims to construct a deep-learning-based auxiliary diagnostic model for early IK diagnosis. Design: A retrospective study. Methods: IK patients with pathological diagnosis were enrolled and their slit-lamp photos were collected. Image augmentation, normalization, and histogram equalization were applied, and five image classification networks were implemented and compared. Model blending technique was used to combine the advantages of single model. The performance of combined model was validated by 10-fold cross-validation, receiver operating characteristic curves (ROC), confusion matrix, Gradient-wright class activation mapping (Grad-CAM) visualization, and t-distributed Stochastic Neighbor Embedding (t-SNE). Three experienced cornea specialists were invited and competed with the combined model on making clinical decisions. Results: Overall, 4830 slit-lamp images were collected from patients diagnosed with IK between June 2010 and May 2021, including 1490 (30.8%) bacterial keratitis (BK), 1670 (34.6%) fungal keratitis (FK), 600 (12.4%) herpes simplex keratitis (HSK), and 1070 (22.2%) Acanthamoeba keratitis (AK). KeratitisNet, the combination of ResNext101_32x16d and DenseNet169, reached the highest accuracy 77.08%. The accuracy of KeratitisNet for diagnosing BK, FK, AK, and HSK was 70.27%, 77.71%, 83.81%, and 79.31%, and AUC was 0.86, 0.91, 0.96, and 0.98, respectively. KeratitisNet was mainly confused in distinguishing BK and FK. There were 20% of BK cases mispredicted into FK and 16% of FK cases mispredicted into BK. In diagnosing each type of IK, the accuracy of model was significantly higher than that of human ophthalmologists ( p

With the rise of global urbanization, the rural built environment has undergone tremendous changes. As such, the rural built environment impacts on residents’ daily travel behavior is getting more researchers’ attention. To date, most of the research focuses on urban areas in developed countries. To understand the state-of-the-art of interplay between the rural built environment and travel behaviors and to identify future research directions, this study adopts a science mapping approach to identify the relevant topics, authors, journals, and countries of the research done. This study proceeds through bibliometric retrieval of articles from 2005, followed by scientometric analysis and qualitative discussion. 37 documents are found to compare urban and rural domains, with 28 on the rural built environment. Research gaps and the research trends are discussed, of which the main themes are multi-dimensional correlation comparison of rural transportation service systems and emerging transportation modes, the influence of rural social and cultural factors on travel behavior, and low-carbon sustainable transportation. This review provides empirical foundation for current state-of-the-art and identifies the future research directions, specifically for rural built environment impact on travel behavior.

Summary: We present a protocol which implements deep learning-based identification of the lung adenocarcinoma category with high accuracy and generalizability, and labeling of the high-risk area on Computed Tomography (CT) images. The protocol details the execution of the python project based on the dataset used in the original publication or a custom dataset. Detailed steps include data standardization, data preprocessing, model implementation, results display through heatmaps, and statistical analysis process with Origin software or python codes.For complete details on the use and execution of this protocol, please refer to Chen et al. (2022). : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Cardiovascular disease is currently one of the most important diseases causing death in China and the world, and acute myocardial infarction is a major cause of cardiovascular disease. This study provides an analytical technique for predicting the prognosis of patients with severe acute myocardial infarction using a support vector machine (SVM) technique based on information gleaned from electronic medical records in the Medical Information Marketplace for Intensive Care (MIMIC)-III database. The MIMIC-III database provided 4785 electronic medical records data for inclusion in the model development after screening 7070 electronic medical records of patients admitted to the intensive care unit for treatment of acute myocardial infarction. Adopting the APS-III score as the criterion for identifying anticipated risk, the dimensions of data information incorporated into the mathematical model design were found using correlation coefficient matrix heatmaps and ordered logistic analysis. An automated prognostic risk-prediction model was developed using SVM, and the fit was evaluated by 5× cross-validation. We used a grid search method to further optimize the parameters and improve the model fit. The excellent generalization ability of SVM was fully verified by calculating the 95% confidence interval of the area under the receiver operating characteristic curve (AUC) for six algorithms (linear discriminant, tree, Kernel Naive Bayes, RUSBoost, KNN, and SVM). Compared to the remaining five models, its confidence interval was the narrowest with higher fitting accuracy and better performance. The patient prognostic risk prediction model constructed using SVM had a relatively impressive accuracy (92.2%) and AUC value (0.98). In this study, a model was designed for fitting that can maximize the potential information to be gleaned in the electronic medical records data. It was demonstrated that SVM models based on electronic medical records data can offer an effective solution for clinical disease prognostic risk assessment and improved clinical outcomes and have great potential for clinical application in the clinical treatment of myocardial infarction.

Muscarinic acetylcholine receptors (mAChRs) are widely expressed in various effector cells and have been proved to play vital roles in smooth muscle contraction and digestive secretion. However, there are relatively few literatures revealing the roles of mAChRs in inflammatory processes, and its underlying regulatory mechanisms have not been elucidated. Taking the advantages of live imaging of zebrafish, we found that inhibition of mAChRs resulted in increased neutrophils recruitment and proinflammatory cytokines expression, whereas activation of mAChRs led to opposite outcome. Subsequently, we found that mAChRs regulated the expression of arginases (args), and pharmacological intervention of args level could reverse the effects of mAChRs on neutrophils migration and cytokines expression, suggesting that args are important downstream proteins of mAChRs that mediate the regulation of inflammatory response. In this study, we identified args as novel downstream proteins of mAChRs in inflammatory responses, providing additional evidence for system immune regulation of cholinergic receptors.

The mammalian oviduct is functionally highly diverse during the estrus cycle. It provides a suitable milieu for oocyte maturation, sperm capacitation, fertilization, early embryo development and transportation. While there have been many studies of molecular mechanisms on the kidding number of goats, a systematic analysis by which the underlying circular RNAs (circRNAs) changes in the oviduct related to prolificacy traits is lacking. Herein, we present a comprehensive circRNA atlas of the oviduct among high- and low-fecundity goats in the follicular phase (FH vs. FL), luteal phase (LH vs. LL), and estrus cycle (FH vs. LH; FL vs. LL) to unravel their potential regulatory mechanisms in improving kidding number. We generated RNA sequencing data, and identified 4,078 circRNAs from twenty sampled Yunshang black goats. Many of these circRNAs are exon-derived and differentially expressed between each comparison group. Subsequently, eight differentially expressed (DE) circRNAs were validated by RT‒qPCR, which was consistent with the RNA-seq data. GO and KEGG enrichment analyses suggested that numerous host genes of DE circRNAs were involved in the hormone secretion, gamete production, fertilization, and embryo development processes. The competing endogenous RNA (ceRNA) interaction network analysis revealed that 2,673 circRNA–miRNA–mRNA axes (including 15 DE circRNAs, 14 miRNAs, and 1,699 mRNAs) were formed, and several target genes derived from the ceRNA network were associated with oviduct functions and reproduction, including SMAD1, BMPR1B, IGF1, REV1, and BMP2K. Furthermore, miR-15a-5p, miR-181b-5p, miR-23b-5p, miR-204-3p, and miR-145-5p might play important roles in reproduction. Finally, a novel circRNA, circIQCG, was identified as potentially involved in embryo development. Overall, our study provides a resource of circRNAs to understand the oviductal function and its connection to prolificacy trait of goats in the differentiation estrus cycle.

Residents’ satisfaction with post-disaster reconstruction in earthquake-stricken areas directly affects their quality of life, which cannot be ignored in post-disaster reconstruction. More than 10 years after the Wenchuan earthquake, we took ten randomly selected villages in the five areas hardest-hit by the Wenchuan earthquake as research objects and obtained 483 valid completed questionnaires. The villagers were randomly sampled and descriptive statistical analysis, factor analysis, and ordered logistic regression were used to explore the factors and relationships influencing villagers’ satisfaction with post-disaster reconstruction in Wenchuan earthquake-stricken areas. The results show that: 1) the more rural residents know about the post-disaster reconstruction, the greater their level of satisfaction; 2) the more the annual income of families increases after resettlement, the greater the satisfaction of rural residents with the post-disaster reconstruction; 3) six public factors, namely the village committee acts as, housing construction quality, public service, policy of benefiting farmers, cultural environment, and hardware environment, all significantly positively affect residents’ overall satisfaction with post-earthquake reconstruction. This study thus enriches the theory of residents’ satisfaction studies and the practice of post-earthquake reconstruction.

PIWI-interacting RNAs (piRNAs), as a novel class of small non-coding RNAs that have been shown to be indispensable in germline integrity and stem cell development. However, the expressed characteristics and regulatory roles of piRNAs during different reproductive phases of animals remain unknown. In this study, we investigated the piRNAs expression profiles in ovaries of sheep during the luteal phase (LP) and follicular phase (FP) using the Solexa sequencing technique. A total of 85,219 and 1,27,156 piRNAs tags were identified in ovine ovaries across the two phases. Most expressed piRNAs start with uracil. piRNAs with a length of 24 nt or 27–29 nts accounted for the largest proportion. The obvious ping-pong signature appeared in the FP ovary. The piRNA clusters in the sheep ovary were unevenly distributed on the chromosomes, with high density on Chr 3 and 1. For genome distribution, piRNAs in sheep ovary were mainly derived from intron, CDS, and repeat sequence regions. Compared to the LP ovary, a greater number of expressed piRNA clusters were detected in the FP ovary. Simultaneously, we identified 271 differentially expressed (DE) piRNAs between LP and FP ovaries, with 96 piRNAs upregulated and 175 piRNAs downregulated, respectively. Functional enrichment analysis (GO and KEGG) indicated that their target genes were enriched in reproduction-related pathways including oocyte meiosis, PI3K-Akt, Wnt, and TGF-β signaling pathways. Together, our results highlighted the sequence and expression characteristics of the piRNAs in the sheep ovary, which will help us understand the roles of piRNAs in the ovine estrus cycle.

Redox-induced magnetic transformation in organic diradicals is an appealing phenomenon. In this study, we theoretically designed twelve couples of diradicals in which two nitroxide (NO) radical groups are connected to the redox-active couplers including p-benzoquinonyl, 1,4-naphthoquinyl, 9,10-anthraquinonyl, naphthacene-5,12-dione, pentacene-6,13-dione, hexacene-6,15-dione, pyrazinyl, quinoxalinyl, phenazinyl, 5,12-diazanaphthacene, 6,13-diazapentacene, and 6,15-diazahexacene. As evidenced at both the B3LYP and M06-2X levels of theory, the calculations reveal that the magnetic reversal can take place from ferromagnetism to antiferromagnetism, or vice versa, by means of redox method in these designed organic magnetic molecules. It was observed that p-benzoquinonyl, 1,4-naphthoquinyl, 9,10-anthraquinonyl, naphthacene-5,12-dione, pentacene-6,13-dione, and hexacene-6,15-dione-bridged NO diradicals produce antiferromagnetism while their dihydrogenated counterparts exhibit ferromagnetism. Similarly, pyrazinyl, quinoxalinyl, phenazinyl, 5,12-diazanaphthacene, 6,13-diazapentacene, and 6,15-diazahexacene-bridged NO diradicals present ferromagnetism while their dihydrogenated counterparts show antiferromagnetism. The differences in the magnetic behaviors and magnetic magnitudes of each of the twelve couples of diradicals could be attributed to their distinctly different spin-interacting pathways. It was found that the nature of the coupler and the length of the coupling path are important factors in controlling the magnitude of the magnetic exchange coupling constant J. Specifically, smaller HOMO-LUMO (HOMO: highest occupied molecular orbital, LUMO: lowest unoccupied molecular orbital) gaps of the couplers and shorter coupler lengths, as well as shorter linking bond lengths, can attain stronger magnetic interactions. In addition, a diradical with an extensively π-conjugated structure is beneficial to spin transport and can effectively promote magnetic coupling, yielding a large |J| accordingly. That is, a larger spin polarization can give rise to a stronger magnetic interaction. The sign of J for these studied diradicals can be predicted from the spin alternation rule, the shape of the singly occupied molecular orbitals (SOMOs), and the SOMO-SOMO energy gaps of the triplet state. This study paves the way for the rational design of magnetic molecular switches.

This study investigated the effects of three feeding systems, indoor feeding (CONT), indoor feeding with time-restricted grazing artificial pasture (4 h/day, G4H), and indoor feeding with an eight-hour daily grazing artificial pasture (G8H), on the growth performance, serum metabolites, ruminal fermentation, and fecal microbiota composition of lambs. Average daily gain showed a tendency (p = 0.081) to be higher for the G4H group compared with the CONT group. Moreover, feeding systems did not have a significant effect on most of the serum biochemical indicators in lambs. Concentrations of serum glutathione peroxidase and immunoglobulins (IgA, gG, and IgM) were significantly lower (p < 0.01) in the CONT group. Additionally, a tendency towards higher levels of volatile fatty acids, acetate, and butyrate was found in animals of the G4H group compared to the CONT group. Furthermore, fecal microbiota composition was altered in G4H and G8H groups, resulting in the increased relative abundance of Firmicutes and Ruminococcaceae UCG-005, as well as the decreased relative abundance of Ruminobacter compared with the CONT group. Overall, these results suggest that indoor feeding with restricted grazing time does not significantly affect fattening performance or rumen fermentation but enhances antioxidation and immune function activity and also alters fecal microbiota composition.

Sperm proteins play vital roles in improving sperm freezing resilience in domestic animals. However, it remains poorly defined which proteins regulate the freezing resilience of spermatozoa in rams (Ovis aries). Here, we compared the proteome of ram sperm with a high cryopreservation recovery ratio (HCR) with that of ram sperm with a low cryopreservation recovery ratio (LCR) using a tandem mass tag-based quantitative proteomics approach. Bioinformatic analysis was performed to evaluate differentially expressed proteins (DEPs). A total of 2464 proteins were identified, and 184 DEPs were screened. Seventy-two proteins were higher in the LCR group. One hundred and twelve proteins were more abundant in the HCR group, and they were mainly involved in the regulation of oxidative phosphorylation and thermogenesis pathways. Proteins in high abundance in the HCR group included the S100A family, such as S100A8, S100A9, S100A14, and S100A16, effectively controlling for CA2+ and maintaining flagella structure; HYOU1 and PRDX1, which participate in antioxidant protection and anti-apoptosis to prevent cell death; and HSP90B1, which maintains cell activity and immune response. Our results could help illuminate the molecular mechanisms underlying cryopreservation of ram semen and expand the potential direction of cryopreservation of high-quality semen.

Growth rate, carcass attributes, and meat quality traits of small ruminants (i.e., sheep and goats) depend on various factors, among which the feeding system is one of the most important factors. However, how feeding systems affect these parameters differ between sheep and goats. Therefore, this review aimed to evaluate the differences in how different feeding systems affect the growth performance, carcass characteristics, and meat quality of sheep and goats. It also explored the effects of a new finishing strategy—time-limited grazing with supplements on these traits. Compared with stalled feeding, finishing lambs/kids on pasture-only feed reduced the average daily gain (ADG) and carcass yield, while supplemented-grazing lambs/kids had near-equivalent or higher ADG and carcass attributes. Pasture-grazing increased the meat flavor intensity and healthy fatty acid content (HFAC) of lamb/kid meat. Supplemental grazing lambs had comparable or superior meat sensory attributes and increased meat protein and HFAC compared to stall-fed ones. In contrast, supplemental grazing only improved the meat color of kids but had little effect on other meat qualities. Moreover, time-limited grazing with supplemental concentrates increased the carcass yield and meat quality in lamb meat. Overall, the effects of different feeding systems on growth performance and carcass traits were comparable between sheep and goats but differed in terms of the meat quality.

Pesticides are essential for the development of agriculture. It is urgent to develop green, safe and efficient pesticides. Bisindole alkaloids have unique and concise structures and broad biological activities, which make them an important leading skeleton in the creation of new pesticides. In this work, we synthesized bisindole alkaloid barakacin in a simple seven-step process, and simultaneously designed and synthesized a series of its derivatives. Biological activity research indicated that most of these compounds displayed good antiviral activities against tobacco mosaic virus (TMV). Among them, compound 14b exerted a superior inhibitory effect in comparison to commercially available antiviral agent ribavirin, and could be expected to become a novel antiviral candidate. Molecular biology experiments and molecular docking research found that the potential target of compound 14b was TMV coat protein (CP). These compounds also showed broad-spectrum anti-fungal activities against seven kinds of plant fungi.

A close association exists among testicular function, gut microbiota regulation, and organismal metabolism. In this study, serum and seminal plasma metabolomes, and the rumen microbiome of sheep with significant differences in sperm viability, were explored. Serum and seminal plasma metabolomes differed significantly between high-motility (HM) and low-motility (LM) groups of sheep, and 39 differential metabolites closely related to sperm motility in sheep were found in seminal plasma metabolomes, while 35 were found in serum samples. A 16S rRNA sequence analysis showed that the relative abundance of HM and LM rumen microorganisms, such as Ruminococcus and Quinella, was significantly higher in the HM group, whereas genera such as Rikenellaceae_RC9_gut_group and Lactobacillus were enriched in the mid-LM group. Serum hormone assays revealed that serum follicle-stimulating hormone (FSH) and MT levels were significantly lower in the LM group than in the HM group, whereas serum glucocorticoid (GC) levels were higher in the LM group than in the HM group, and they all affected sperm motility in sheep. Ruminococcus and other rumen microorganisms were positively correlated with sperm motility, whereas Lactobacillus was negatively correlated with FSH and GCs levels. Our findings suggest that rumen microbial activity can influence the host metabolism and hormone levels associated with fertility in sheep.

Emerging evidence shows that m6A is the most abundant modification in eukaryotic RNA molecules. It has only recently been found that this epigenetic modification plays an important role in many physiological and pathological processes, such as cell fate commitment, immune response, obesity, tumorigenesis, and relevant for the present review, gametogenesis. Notably the RNA metabolism process mediated by m6A is controlled and regulated by a series of proteins termed writers, readers and erasers that are highly expressed in germ cells and somatic cells of gonads. Here, we review and discuss the expression and the functional emerging roles of m6A in gametogenesis and early embryogenesis of mammals. Besides updated references about such new topics, readers might find in the present work inspiration and clues to elucidate epigenetic molecular mechanisms of reproductive dysfunction and perspectives for future research.

ObjectiveTo evaluate the clinical features and inflammatory cytokines of dry eye disease (DED) in patients with schizophrenia.MethodsThis is a case-control study. The modified self-rating depression scale (M-SDS) and the ocular surface disease index (OSDI) were used to evaluate the symptoms of depression and DED, respectively. Lipid layer thickness (LLT), partial blink rate (PBR), meibomian gland loss (MGL), tear break-up time (TBUT), corneal fluorescein staining, Schirmer I-test, and eyelid margin abnormalities were also measured. A multiplex ELISA Quantibody array was used to detect the inflammatory cytokines in the tears of all participants.ResultsForty schizophrenic patients and 20 control subjects were included. The mean age was 45.0 ± 9.5 years (range, 22–63 years) in schizophrenic patients and 45.4 ± 16.2 years (range, 23–76 years) in controls (P = 0.914). The ratio of male to female was 1.1 in schizophrenic patients and 1.0 in controls (P = 0.914). Ten women (52.6%) with schizophrenia and 2 (20%) in the control group (P = 0.096) were menopausal or post-menopausal. The OSDI [0.0 (0.0–4.2) vs. 7.3 (2.1–14.6)] and TBUT [4.5 (3.0–6.0) vs. 10.0 (3.5–11.0)] were significantly lower in patients with schizophrenia than in controls (P = 0.003 and P = 0.009, respectively). The rate of MGL [36.5 (17.5–47.5) vs. 8.5 (0.0–17.5)] increased in schizophrenic patients (P < 0.001). Among pro-inflammatory cytokines, the levels of interleukin (IL)-1α, IL-6, IL-11, IL-12A, IL-15, IL-17A, and granulocyte colony-stimulating factor (G-CSF) in tears were elevated in the schizophrenia group (all P < 0.01). Most of the chemokines examined were at increased levels in the tears of schizophrenics (all P < 0.05). The levels of matrix metalloproteinases-9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1) were also higher in the schizophrenic patients (all P < 0.001). The concentrations of IL-1Ra, tissue-inhibitor of metalloproteinase-1 (TIMP-1), and TIMP-2 in the schizophrenia group were decreased (all P < 0.001). In schizophrenic patients, the level of CCL2 in tears was positively correlated with OSDI (R = 0.34, P = 0.03). The increasing TIMP-1 and decreasing IL-5 were correlated with increasing LLT (R = 0.33, P = 0.035; R = −0.35, P = 0.027, respectively). The level of ICAM-1 was then positively correlated with partial blink rate (PBR) (R = 0.33, P = 0.035). There was a negative correlation between IL-8 and the Schirmer I-test (R = −0.41, P = 0.009).ConclusionsPatients with schizophrenia were more likely to experience asymptomatic DED, with mild symptoms and obvious signs. The inflammatory cytokines in the tears of schizophrenic patients differed greatly from that of non-schizophrenic patients.

Targeted muscle reinnervation (TMR) is a microsurgical repair technique to reconstruct the anatomical structure between the distal nerve and the muscle stump to provide more myoelectric information to the artificially intelligent prosthesis. Postoperative functional electrical stimulation treatment of the patient’s denervated muscle or proximal nerve stump as well as nerve growth factor injection is effective in promoting nerve regeneration and muscle function recovery. In this experiment, we successfully established a TMR rat model and divided Sprague-Dawley (SD) adult male rats into TMR group, TMR + FES group, and TMR + NGF group according to TMR and whether they received FES treatment or NGF injection after surgery, and the recovery effect of rat neuromuscular function was assessed by analyzing EMG signals. Through the experiments, we confirmed that growth factor supplementation and low-frequency electrical stimulation can effectively promote the regeneration of the transplanted nerve as well as significantly enhance the motor function of the target muscle and have a positive effect on the regeneration of the transplanted nerve.

TRPM2 (transient receptor potential melastatin-2), a Ca2+ permeable, non-selective cation channel, is highly expressed in cancers and regulates tumor cell migration, invasion, and proliferation. However, no study has yet demonstrated the association of TRPM2 with the prognosis of cancer patients or tumor immune infiltration, and the possibility and the clinical basis of TRPM2 as a prognostic marker in cancers are yet unknown. In the current study, we first explored the correlation between the mRNA level of TRPM2 and the prognosis of patients with different cancers across public databases. Subsequently, the Tumor Immune Estimation Resource (TIMER) platform and the TISIDB website were used to assess the correlation between TRPM2 and tumor immune cell infiltration level. We found that 1) the level of TRPM2 was significantly elevated in most tumor tissues relative to normal tissues; 2) TRPM2 upregulation was significantly associated with adverse clinical characteristics and poor survival of kidney renal clear cell carcinoma (KIRC) patients; 3) the level of TRPM2 was positively related to immune cell infiltration. Moreover, TRPM2 was closely correlated to the gene markers of diverse immune cells; 4) a high TRPM2 expression predicted worse prognosis in KIRC based on different enriched immune cell cohorts; and 5) TRPM2 was mainly implemented in the T-cell activation process indicated by Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. In conclusion, TRPM2 can serve as a marker to predict the prognosis and immune infiltration in KIRC through the regulation of T-cell activation. The current data may provide additional information for further studies surrounding the function of TRPM2 in KIRC.

Category: Basic Sciences/Biologics; Diabetes Introduction/Purpose: Charcot neuroarthropathy (CNA) is a destructive joint condition secondary to neuropathic deficiency. For more than a century, the pathogenesis of CNA has been interpreted as unprotected injury and/or uncontrollable inflammation in a neuropathic joint, with little understanding its cellular and molecular pathology. Histologically, a hallmark of CNA is bone and cartilage fragments engulfed by hyperplastic synovium. Synovium is richly innervated. Neuropeptides, such as calcitonin gene- related peptide (CGRP), are secreted by neuronal and non-neuronal cells of the nervous, endocrine, and immune systems, and regulate inflammation. This study investigated the expression of CGRP in the synovial samples collected from CNA and non-CNA joint conditions, and the effects of CGRP on the proliferation and collagenolysis of fibroblast-like synoviocytes (FLS) isolated from CNA synovium in vitro. Methods: For this study, six CNA and 14 non-CNA synovial samples were collected during foot and ankle surgery. The donors included 10 male and 10 female, age from 14 to 79 years (mean 48). The non-CNA conditions consisted of osteoarthritis, ankle instability, Os Trigonum and osteochondritis dissecans. Western blot and immunohistochemistry of CGRP were performed to detect and localize CGRP expression in the CNA and non- CNA synovium. FLS was isolated from CNA synovium and cultured with, or without, human CGRP (10nM) in the culture media, for comparison of cell proliferation. Additionally, FLS were seeded on the collagen-coated 24-well plate and simulated with CGRP (10nM) and recombinant human tumor necrosis factor-alpha (TNF-α). After 7 days, the residual collagen on the bottom of the culture plate were stained and imaged for area measurements. Data were analyzed with t test or one-way Analysis of Variance, followed with post hoc Tukey's test. Results: By western blot, there was significant CGRP expression in the CNA synovium (5/6; Fig1). Except of an intense CGRP band in one of the osteoarthritis samples, only recognizable CGRP bands were shown in the samples of other non-CNA conditions. The average density of CGRP (in greyscale) in the CNA group was about 2-fold of that in the non-CNA group (10126 +- 5346 vs. 5377+-3734; p < 0.05). Immunohistochemistry demonstrated intense CGRP staining in the intimal layer of the CNA synovium (arrows) but not in the non-CNA synovium (Fig1). Treated with CGRP, the number of FLS in tissue culture increased. Cell number doubling time was 1.0 day (+-0.4) for the CGRP treated FLS and 2.2 days (+-0.5) for the control (p < 0.05). When the culture media were supplemented with CGRP and TNF-α, FLS eroded a larger area of collagen coating comparing with TNF-α alone in the media (p < 0.05). Conclusion: A knowledge gap in understanding the molecular and cellular pathology of CNA hampers the development of disease-modifying therapies. This study showed an increased CGRP, with a concentration in the intimal layer, in the CNA synovium as compared with the synovium in the non-CNA foot conditions. The increased CGRP expression in CNA synovium may be part of the unbalanced neuropeptide signaling in the neuropathic pathology. Functionally, CGRP stimulated FLS proliferation and degrading collagen in vitro. These effects suggest that CGRP may play a role in bone and joint destruction in the Charcot foot.

Category: Ankle; Ankle Arthritis; Other Introduction/Purpose: Periprosthetic infection is a devastating complication in total ankle arthroplasty (TAA). Measures that can reduce or eliminate infection occurrence are warranted for further investigation, particularly if they also minimize added costs, operative time or potential adverse effects. There remains insufficient evidence to show definitive benefits or risks associated with use of local antibiotics such as vancomycin for infection prevention. The purpose of this study was to determine the effects of topical vancomycin powder application in TAA and whether it may decrease infection rate in the subacute postoperative period. To our knowledge, this is the first comparative study in a general population undergoing TAA. Methods: A retrospective study was conducted based on a consecutive series of patients who underwent TAA performed by a single senior surgeon. The control group without vancomycin powder was matched to the study group that received application over the implants prior to closure, which was based on when the surgeon transitioned to usage in all patients. Various demographic data for the patients was collected. Only patients with a minimal follow up of 80 days were included in order to capture the perioperative period of infection. Infection rate was based on a definition of deep infection necessitating inpatient hospitalization for IV antibiotics and/or surgical intervention. The associations of various demographic factors and vancomycin application with infection rate were calculated with chi square and odds ratio. Significance level was set to 0.05. Results: A total of 252 patients (n=103 without, and 149 with vancomycin powder) were included in the study. The overall infection rate was 3.2%, which was not correlated with a history of diabetes, BMI, additional concurrent surgery, or age, but was associated with current positive smoking status (p=0.03). The infection rates between the groups that received or did not receive vancomycin powder were not statistically significantly different (2.7% vs 3.9%, respectively, p=0.59). The odds ratio (OR) of infection with vancomycin powder was not statistically significant either, at OR=0.68 (95% CI 0.17-2.81). However, the vancomycin group did have a significantly higher number of patients with previous wound issues (12 vs. 2; p=0.04) and infection (7 vs. 0; p=0.04) as well as concomitant surgeries (81 vs. 41; p=.02). Conclusion: The consequences of periprosthetic TAA infection are substantial, and the risks should be mitigated. Although this study did not detect a statistically significant difference in infection rates between patients who received or did not receive vancomycin powder, there was a trend towards risk reduction by about 30%. In addition, current smoking was found to be significantly associated with higher rates of infection and smoking cessation can serve as another point of intervention. As the complexity of patient factors and indications for performing total ankle arthroplasty expand, vancomycin powder offers a relatively cost-effective, safe, and convenient option to potentially reduce infection.

Category: Other; Ankle; Arthroscopy; Bunion; Hindfoot; Lesser Toes; Midfoot/Forefoot; Trauma Introduction/Purpose: The COVID-19 pandemic has brought a major increase in telemedicine utilization to conserve resources and maintain social distancing. The rapid transition over a short period of time has exposed challenges and limitations of virtual visits, especially with regards to performing an effective and efficient physical examination. Within months, orthopedic telemedicine guides were published for patient education and facilitating the musculoskeletal examination. These publications, however, included only a short video clip to explain to the patient how to participate in the examination during a telemedicine visit. In the foot and ankle subspecialty, the closely adjacent complex anatomy compared to other areas of the body presents unique challenges for physical exam. Methods: To optimize the efficiency and efficacy of the examination portion of the visit for both patients and providers, we designed and recorded an instructional video that is sent to all patients by email a minimum of 1 week prior to their appointment. This video consists of a step-by-step guide on how to take suitable photos and videos of their feet and ankles for the physical examination portion of their visit. These media files are then directly uploaded by the patients into their EMR or emailed to the physician's office to be uploaded for access by the provider before and during the virtual visit. Along with the video, patients are given a link to test their microphone and camera in advance of the visit to ensure adequate functionality and positioning. Results: Our pre-appointment instructional video has been effective to methodically replicate the most important aspects of an in-person foot and ankle evaluation. Both physicians and patients appear to benefit from the tutorial video by having more time during the telemedicine visit to focus on history, assessment, and plan. Patients are more actively involved in the clinical data collection process because they are educated on what to expect and how to best prepare and participate in telemedicine visits. Moreover, having a set of systematic and detailed photos and recordings of the patient's foot and ankle beforehand better focuses interaction and discussion with the patient during the telemedicine encounter. Additionally, these are saved into the patient's electronic medical record, available for reference and later review. Conclusion: Physical examination plays a critical role in diagnosis and treatment in the orthopedic foot and ankle subspecialty. More research is needed to discern how best to utilize virtual modalities as they become more commonplace, not just from the imposition from the COVID pandemic but also from the standpoint of patient convenience and time efficiency. Here we have described our creation of a pre-visit educational video to guide and engage patients on acquiring invaluable physical examination information for the orthopedic foot and ankle telemedicine encounter.

Silica is widely applied in industrial fields due to its good properties, while preparation of high-quality SiO2 by carbonization is an important way to utilize CO2. The experiment was carried out in a microbubble/bubbling experimental device, with its mass transfer kinetics of carbonization analyzed according to the pH-t curves. Under microbubble conditions, with the increasing temperature of 20∼60°C, the specific surface area, oil absorption value and particle size of silica varies at 336.80∼231.29 m2/g, 1.12∼1.81 ml/g and 16.49∼14.60 μm, respectively, which is similar as that with bubble. Aging at 20∼90 °C, they involve in the range of 35.82∼128.76 m2/g, 1.59∼2.44 ml/g and 23.15∼14.46 μm. With total concentration of solution >0.5 M, the concentration increases, the specific surface area and particle size of microbubbles are larger than those of the bubbling silica, and oil absorption value increases at 1.81∼2.44 ml/g. The kinetic analysis shows that it is more consistent with theoretical value, which can be judged as the secondary-reaction process. The microbubbles increase the CO2 utilization rate and volumetric mass transfer coefficient of carbonization by 2-4 times, while the liquid-phase mass transfer coefficient decreases. It indicates that microbubble mass transfer is achieved by significantly increasing the specific surface area.

The oviduct is a dynamic reproductive organ for mammalian reproduction and is required for gamete storage, maturation, fertilization, and early embryonic development, and it directly affects fecundity. However, the molecular regulation of prolificacy occurring in estrous periods remain poorly understood. This study aims to gain a better understanding of the genes involved in regulating goat fecundity in the proteome and transcriptome levels of the oviducts. Twenty female Yunshang black goats (between 2 and 3 years old, weight 52.22 ± 0.43 kg) were divided into high- and low-fecundity groups in the follicular (FH and FL, five individuals per group) and luteal (LH and LL, five individuals per group) phases, respectively. The DIA-based high-resolution mass spectrometry (MS) method was used to quantify proteins in twenty oviducts. A total of 5409 proteins were quantified, and Weighted gene co-expression network analysis (WGCNA) determined that the tan module was highly associated with the high-fecundity trait in the luteal phase, and identified NUP107, ANXA11, COX2, AKP13, and ITF140 as hub proteins. Subsequently, 98 and 167 differentially abundant proteins (DAPs) were identified in the FH vs. FL and LH vs. LL comparison groups, respectively. Parallel reaction monitoring (PRM) was used to validate the results of the proteomics data, and the hub proteins were analyzed with Western blot (WB). In addition, biological adhesion and transporter activity processes were associated with oviductal function, and several proteins that play roles in oviductal communication with gametes or embryos were identified, including CAMSAP3, ITGAM, SYVN1, EMG1, ND5, RING1, CBS, PES1, ELP3, SEC24C, SPP1, and HSPA8. Correlation analysis of proteomics and transcriptomic revealed that the DAPs and differentially expressed genes (DEGs) are commonly involved in the metabolic processes at the follicular phase; they may prepare the oviductal microenvironment for gamete reception; and the MAP kinase activity, estrogen receptor binding, and angiotensin receptor binding terms were enriched in the luteal phase, which may be actively involved in reproductive processes. By generating the proteome data of the oviduct at two critical phases and integrating transcriptome analysis, we uncovered novel aspects of oviductal gene regulation of fecundity and provided a reference for other mammals.

The oviduct is associated with embryo development and transportation and regulates the pregnancy success of mammals. Previous studies have indicated a molecular mechanism of lncRNAs in gene regulation and reproduction. However, little is known about the function of lncRNAs in the oviduct in modulating goat kidding numbers. Therefore, we combined RNA sequencing (RNA-seq) to map the expression profiles of the oviduct at the luteal phase from high- and low-fecundity goats. The results showed that 2023 differentially expressed mRNAs (DEGs) and 377 differentially expressed lncRNAs (DELs) transcripts were screened, and 2109 regulated lncRNA-mRNA pairs were identified. Subsequently, the genes related to reproduction (IGF1, FGFRL1, and CREB1) and those associated with embryonic development and maturation (DHX34, LHX6) were identified. KEGG analysis of the DEGs revealed that the GnRH- and prolactin-signaling pathways, progesterone-mediated oocyte maturation, and oocyte meiosis were related to reproduction. GSEA and KEGG analyses of the target genes of DELs demonstrated that several biological processes and pathways might interact with oviduct functions and the prolificacy of goats. Furthermore, the co-expression network analysis showed that XLOC_029185, XLOC_040647, and XLOC_090025 were the cis-regulatory elements of the DEGs MUC1, PPP1R9A, and ALDOB, respectively; these factors might be associated with the success of pregnancy and glucolipid metabolism. In addition, the GATA4, LAMA2, SLC39A5, and S100G were trans-regulated by lncRNAs, predominantly mediating oviductal transport to the embryo and energy metabolism. Our findings could pave the way for a better understanding of the roles of mRNAs and lncRNAs in fecundity-related oviduct function in goats.