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High-performance automated detection methods for epilepsy play a crucial role in clinical diagnostic support. To address the challenge of effectively extracting features from epileptic EEG signals, characterized by strong spontaneity and complexity, a novel feature extraction approach based on Window Kullback-Leibler Divergence (WKLD) is proposed, coupled with discrete wavelet analysis for EEG signal feature extraction. Then, a Residual Multidimensional Taylor Network (ResMTN) classifier is applied for epilepsy state classification. Experimental results demonstrate an accuracy of 98% in classifying EEG signals during seizure and interictal periods, with both specificity and sensitivity reaching 98.18%, outperforming existing widely-used feature extraction and classification methods.

Users often experience motion sickness symptoms after using Virtual Reality (VR) systems, which can jeopardize their health. If we can rapidly diagnose the vertigo levels of VR users and dynamically take anti-motion sickness measures based on the levels, such as adjusting the movement of objects in VR glasses, adding visual reference points, and changing image brightness, contrast, and refresh rate, we can quickly alleviate motion sickness symptoms. Therefore, rapid assessment of the VR vertigo levels becomes crucial. Deep learning methods can accurately diagnose vertigo levels, but due to the complex structure and high computational requirements of these deep models, they may not fully meet the need for speed. Additionally, these complex models may be challenging to implement in devices like VR glasses. Unlike deep neural networks, BP-MTN represents complex nonlinear functions as polynomial functions using a simple network structure based solely on addition and multiplication operations. This design significantly reduces model complexity. However, traditional MTN models are primarily used for prediction tasks and are not suitable for classification. To address this issue, this paper proposes a Backpropagation Multivariate Taylor Network (BP-MTN) classifier for diagnosing VR vertigo levels. Compared to the traditional MTN, the BP-MTN includes the following modifications: 1) adding fully connected layers to handle inconsistent input and output dimensions of the BP-MTN; 2) introducing a softmax layer after the traditional MTN’s output layer to enable classification; 3) incorporating activation functions after each output node to enhance the model’s ability for fitting nonlinearity. Experimental results demonstrate that the BP-MTN classifier achieves higher classification accuracy and faster speed compared to some deep learning models.

Tacit knowledge is the kind of knowledge that is difficult to transfer to another person by means of writing it down or verbalizing it. In the mineral grinding process, the proficiency of the operators depends on the tacit knowledge gained from their experience and training rather than on knowledge learned from a handbook. This article proposed a method combining the electroencephalogram (EEG) signals and the industrial process to detect the proficiency of the operators in the mineral grinding process to reveal the effect of tacit knowledge on the functional cortical connection. The functional brain networks of operators were established based on partial direct coherence and directed transfer function of EEG, and the multi-classifiers were used with the graph-theoretic indexes of the FBNs as input to distinguish the trained operators (Hps) from the non-trained operators (Lps). The results showed that the brain networks of Hps had a better connectivity than those of Lps (p < 0.01), and the accuracy of classification was up to 94.2%. Our studies confirm that based on the performance of EEG features and the combination of industrial operational operation and cognitive processes, the proficiency of the operators can be detected.

PurposeWe aimed to report the latest and largest pooled analyses and evidence updates to assess the effectiveness of telemedicine interventions for self-management (DSM) in patients with type 2 diabetes mellitus (T2DM).MethodsA systematic literature search was conducted using PubMed, Cochrane, Embase, and Web of Science in December 2023. We included randomized controlled trials (RCTs) of adults (≥18 years of age) diagnosed with T2DM where the intervention was the application of telemedicine. The Cochrane Risk of Bias Assessment was used to evaluate quality. The study’s main outcome indicators were glycosylated hemoglobin (HbA1c) and diabetes self-management (DSM) capacity.ResultsA total of 17 eligible articles, comprising 20 studies and 1,456 patients (734 in the intervention group and 722 in the control group), were included in the evidence synthesis. The baseline characteristics of both groups were similar in all outcomes. Comprehensive analyses showed post-intervention decreases in HbA1c, 2-h postprandial glucose, systolic and diastolic blood pressure, increases in Diabetes Self- Care activities, DSM competencies based on dietary and medication adherence, and improvements in overall DSM scores, all of which were statistically significant. While no statistically significant differences were observed in body mass index, lipids, and other DSM dimensions. Based on subgroup analyses, app-based experimental interventions targeting under 60 years old populations in Asia and North America were found to be more effective and less heterogeneity in the short term (

As the quality of life improves, the incidence of diabetes mellitus and its microvascular complications (DMC) continues to increase, posing a threat to people’s health and wellbeing. Given the limitations of existing treatment, there is an urgent need for novel approaches to prevent and treat DMC. Autophagy, a pivotal mechanism governing metabolic regulation in organisms, facilitates the removal of dysfunctional proteins and organelles, thereby sustaining cellular homeostasis and energy generation. Anomalous states in pancreatic β-cells, podocytes, Müller cells, cardiomyocytes, and Schwann cells in DMC are closely linked to autophagic dysregulation. Natural products have the property of being multi-targeted and can affect autophagy and hence DMC progression in terms of nutrient perception, oxidative stress, endoplasmic reticulum stress, inflammation, and apoptosis. This review consolidates recent advancements in understanding DMC pathogenesis via autophagy and proposes novel perspectives on treating DMC by either stimulating or inhibiting autophagy using natural products.

Background: Type 2 innate lymphoid cells (ILC2s) and NLRP3 inflammasome are related to allergic and inflammatory responses. NLRP3 inflammasome inhibitor MCC950 was demonstrated to ameliorate allergic rhinitis (AR) in animal models.Objective: To elucidate the effect of MCC950 on ILC2 responses in AR.Methods: NLRP3 inflammasome, ILC2s, IL-5+ILC2s, IL-13+ILC2s, and Th2-related factors were examined in 30 AR patients. ILC2s were identified as Lin-CRTH2+CD127+lymphocytes. ILC2s isolated from PBMCs were stimulated with LPS plus ATP. The effect of MCC950, IL-1β, and IL-18 on ILC2 responses was detected by flow cytometry. AR models were established in 60 BALB/c mice. Nasal symptoms and ILC2 responses in the AR models after MCC950 treatment were detected. Human nasal epithelial cells were stimulated with IL-13 (10 ng/mL) and treated with MCC950 (10 μM).Results: AR patients showed activated NLRP3 inflammasome and increased ILC2 responses compared to controls. NLRP3 inflammasome levels in the AR patients were positively related to the proportion of ILC2s, IL-5+ILC2s, and IL-13+ILC2s in total PBMCs. MCC950 treatment or IL-1β/IL-18 suppression inhibited ILC2 proliferation and Th2-related factors (GATA3, RORα, IL-5, and IL-13). MCC950 administration alleviated frequencies of nasal rubbing and sneezes in the AR models. ILC2s, IL-5+ILC2s, and IL-13+ILC2s in mice were reduced by MCC950. MCC950 inhibited NLRP3 inflammasome in the in vitro models of AR.Conclusion: MCC950 inhibited ILC2 responses in AR and mice models, suggesting that blocking NLRP3 inflammasome may be a promising target for AR clinical treatment.

Powder metallurgy is widely used to fabricate high-nitrogen, nickel-free austenitic stainless steel. However, after sintering and nitriding, additional solution treatment is typically required to achieve uniform nitrogen distribution and a homogeneous austenite phase. This work proposes a novel method to eliminate the need for lengthy and high-temperature solution treatment by switching the nitrogen atmosphere to argon during the cooling process. The effects of different N2-Ar atmosphere-switching temperatures (750–1320 °C) on the phase composition, element distribution, microstructure, mechanical properties, and corrosion resistance of the studied steels were systematically investigated. Results show that cooling in the N2 atmosphere initially transforms the matrix to a fully austenitic structure enriched with nitrogen. Excessive nitrogen infiltration leads to Cr2N precipitation, inducing partial austenite decomposition and forming a multiphase structure comprising austenite, α-Fe, and Cr2N. Strategic switching from N2 to Ar reverses this reaction, yielding a high-nitrogen, chemically uniform austenitic structure. Specifically, switching at 1150 °C, the steel exhibits excellent mechanical properties and corrosion resistance, with a yield strength of 749 MPa, an ultimate tensile strength of 1030 MPa, an elongation of 38.7%, and a corrosion current of 0.06 mA/cm2, outperforming the steels cooled solely in N2 and subsequently solution-treated. This novel method offers advantages in cost reduction, energy saving, and operational effectiveness, highlighting its potential for broad industrial application.

Background. Serum uric acid (SUA) and glycosylated hemoglobin (HbA1c) were closely related to the body’s metabolism. This study aimed to investigate the relationship between HbA1c and SUA in adults. Methods. This study selected 7293 participants aged ≥20 from 2011 to 2020 in the National Health and Nutrition Examination Survey (NHANES). The multivariate linear regression model was used to test the association between HbA1c and SUA. Subgroup analysis was performed according to age, gender, race, and body mass index (BMI). This study solved the relationship between HbA1c and SUA by fitting a smooth curve. Finally, the inflection point in the nonlinear relationship was calculated by the recursive algorithm, and the relationship between HbA1c and SUA on both sides of the inflection point was analyzed by the two-segment piecewise linear regression model. Results. All 7293 participants found a negative correlation between HbA1c and SUA by completely adjusting the model (β = −7.93 and 95% CI: −9.49–−6.37). In addition, when this study was stratified by gender, age, race, and BMI status, this negative correlation was still statistically significant. In the subgroup analysis, we found that the relationship between the two had different results due to gender differences. In men, HbA1c had a significant negative correlation with SUA. However, in women, the HbA1c value was positively correlated with SUA before 6.8%, and the HbA1c value was negatively correlated with SUA after 6.8%, which indicates that the relationship between HbA1c and SUA in women has changed in prediabetes and diabetes. Conclusion. This study shows that HbA1c is positively correlated with SUA in American adults before 7%. There is a negative correlation after the HbA1c value of 7%.

Objective: Postmenopausal osteoporosis (PMOP) is a common systemic metabolic bone disorder that is owing to the reduced estrogen secretion and imbalance of bone absorption and bone formation in postmenopausal women. Ferroptosis has been identified as a novel modulatory mechanism of osteoporosis. Nevertheless, the particular modulatory mechanism between ferroptosis and PMOP is still unclear. The objective of the current investigation was to detect potential biomarkers connected to ferroptosis in PMOP and discover its probable mechanism through bioinformatics. Methods: We downloaded PMOP-related microarray datasets from the database of Gene Expression Omnibus (GEO) and obtained the differentially expressed genes (DEGs). Utilizing bioinformatics analysis, the DEGs were intersected with the ferroptosis dataset to obtain ferroptosis-connected mRNAs. Enrichment analysis employing KOBAS 3.0 was conducted to comprehend the biological functions and enrichment pathways of the DEGs. The generation of the protein-protein interaction (PPI) network was conducted with the aim of identifying central genes. Lastly, the coexpression and competitive endogenous RNA (ceRNA) networks were built using Cytoscape. With the help of external datasets GSE56815 to verify the reliability of the hub genes by plotting ROC curves. Results: We identified 178 DE microRNAs (miRNAs), 138 DE circular RNAs (circRNAs), and 86 ferroptosis-related mRNAs. Enrichment analysis exhibited that mRNAs were primarily connected with the signaling pathways of PI3K/Akt, metabolism, mTOR, FoxO, HIF-1, AMPK, MAPK, ferroptosis, VEGF, and NOD-like receptors. Generation of the PPI network detected eight hub genes. The circRNA/miR-23b-3p/PTEN axis may relieve PMOP by inhibiting ferroptosis through targeting the pathway of PI3K/Akt signaling, which is a vital modulatory pathway for PMOP progression. Moreover, the ROC curves ultimately indicates that the four hub genes have greater diagnostic importance in PMOP samples in contrast to the normal group samples, which may be possible markers for PMOP diagnosis. Conclusions: Bioinformatics analysis identified four hub genes, namely, PTEN, SIRT1, VEGFA, and KRAS, as potential biomarkers for PMOP diagnosis and management. Moreover, the circRNA/miR-23b-3p/PTEN axis may relieve PMOP by suppressing ferroptosis through targeting the pathway of PI3K/Akt signaling, providing a new avenue to explore the pathogenesis of PMOP.

Abstract Introduction With the spread of the epidemic worldwide, an increasing number of doctors abroad have observed the following atypical symptoms of coronavirus disease 2019 (COVID‐19): olfactory or taste disorders. Therefore, clarifying the incidence and clinical characteristics of olfactory and taste disorders in Chinese COVID‐19 patients is of great significance and urgency. Materials and Methods A retrospective study was conducted, which included 229 severe acute respiratory syndrome coronavirus 2 confirmed patients, through face‐to‐face interviews and telephone follow‐up. Following the completion of questionnaires, the patients participating in the study, were categorized according to the degree of olfactory and taste disorders experienced, and the proportion of each clinical type of patient with olfactory and taste disorders and the time when symptoms appeared were recorded. Results Among the 229 patients, 31 (13.54%) had olfactory dysfunction, and 44 (19.21%) had gustatory dysfunction. For the patients with olfactory dysfunction, 6 (19.35%) developed severe disease and became critically ill. Olfactory dysfunction appeared before the other symptoms in 21.43% of cases. The proportion of females with olfactory and gustatory dysfunction was higher than that of males (P

Objective We aimed to develop a nomogram to predict risk of resistance to intravenous immunoglobulin (IVIG) in children with Kawasaki disease in eastern China. Methods We retrospectively analysed the data of children with Kawasaki disease who received IVIG during hospitalisation at Soochow University Affiliated Children’s Hospital. IVIG resistance was defined as recrudescent or persistent fever ≥36 h after the end of the IVIG infusion. Baseline variables were analysed using least absolute shrinkage and selection operator (LASSO) to identify the predictors of IVIG resistance, which were then used to construct a predictive nomogram. Calibration curve and area under the receiver operating characteristic curve (AUC) were used to evaluate the performance of the model. The predictive nomogram was validated on test sets of external data and prospective data. Results Between January 2015 and December 2020, 1293 Kawasaki disease patients were hospitalized in Soochow University Affiliated Children’s Hospital. Among them, 72 (5.57%) showed IVIG resistance. LASSO identified haemoglobin, percentage of neutrophils, C-reactive protein level, platelet count, serum albumin, serum sodium, serum alkaline phosphatase, coronary artery damage, and complete Kawasaki disease as risk factors for IVIG resistance. The nomogram constructed using these factors showed satisfactory discriminatory power (AUC, 0.75), and sensitivity (0.74) and specificity (0.64). In the external data and prospective data, the AUC was 0.66 and 0.83, respectively, the sensitivity was 0.86 and 1, respectively, and the specificity was 0.49 and 0.60, respectively. Conclusions The predictive nomogram constructed using nine factors associated with IVIG resistance in children with Kawasaki disease could be a useful tool for identifying patients likely to show IVIG resistance. This nomogram may help reduce the risk of coronary artery lesions.Key Messages None of the IVIG resistance scoring systems has shown consistently good performance in previous studies. Tools to predict the risk of IVIG resistance in eastern China are lacking. In our series, haemoglobin level, percentage of neutrophils, platelet count, coronary artery damage, incomplete Kawasaki disease, and CRP, serum albumin, serum sodium, and serum alkaline phosphatase levels were risk factors of IVIG resistance in hospitalized children in the eastern China cities of Suzhou and Fuzhou. We propose an easy-to-use nomogram to predict the risk factors of IVIG resistance in hospitalized children.

Southwestern North America (SWNA) continuously experienced megadroughts and large wildfires in 2020 and 2021. Here, we quantified their impact on the terrestrial carbon budget using net biome production (NBP) estimates from an ensemble of atmospheric inversions assimilating in-situ CO _2 and Carbon Observatory – 2 (OCO-2) satellite XCO _2 retrievals (OCO-2 v10 MIP Extension), two satellite-based gross primary production (GPP) datasets, and two fire CO _2 emission datasets. We found that the 2020 – 2021 drought and associated wildfires in SWNA led to a large CO _2 loss, an ensemble mean of 95.07 TgC estimated by the satellite inversions using both nadir and glint XCO _2 retrievals (LNLG) within the OCO-2 v10 MIP, greater than 80% of SWNA’s annual total carbon sink. Moreover, the carbon loss in 2020 was mainly contributed by fire emissions while in 2021 mainly contributed by drought impacts on terrestrial carbon uptake. In addition, the satellite inversions indicated the huge carbon loss was mainly contributed by fire emissions from forests and grasslands along with carbon uptake reductions due to drought impacts on grasslands and shrublands. This study provides a process understanding of how some droughts and following wildfires affect the terrestrial carbon budget on a regional scale.

Abstract Trueperella pyogenes (T. pyogenes) is an opportunistic pathogen associated with a variety of diseases in many domestic animals. Therapeutic treatment options for T. pyogenes infections are becoming limited due to antimicrobial resistance, in which efflux pumps play an important role. This study aims to evaluate the inhibitory activity of luteolin, a natural flavonoid, on the MsrA efflux pump and investigate its mechanism. The results of antimicrobial susceptibility testing indicated that the susceptibility of msrA-positive T. pyogenes isolates to six macrolides increased after luteolin treatment, while the susceptibility of msrA-negative isolates showed no change after luteolin treatment. It is suspected that luteolin may increase the susceptibility of T. pyogenes isolates by inhibiting MsrA activity. After 1/2 MIC luteolin treatment for 36 h, the transcription level of the msrA gene and the expression level of the MsrA protein decreased by 55.0–97.7% and 36.5–71.5%, respectively. The results of an affinity test showed that the equilibrium dissociation constant (KD) of luteolin and MsrA was 6.462 × 10–5 M, and hydrogen bonding was predominant in the interaction of luteolin and MsrA. Luteolin may inhibit the ATPase activity of the MsrA protein, resulting in its lack of an energy source. The current study illustrates the effect of luteolin on MsrA in T. pyogenes isolates and provides insight into the development of luteolin as an innovative agent in combating infections caused by antimicrobial-resistant bacteria.

Background. Serum uric acid (SUA) was closely related to body metabolism. This study aimed to investigate the relationship between the adult weight-adjusted waist index (WWI) and SUA. Methods. In the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2020, 6494 eligible participants aged ≥20 were included. The multivariate logistic regression model was used to test the correlation between WWI and SUA. At the same time, subgroup analysis was carried out by using multivariate logistic regression according to age, sex, and race. Then, the fitting smooth curve was applied to solve the association between WWI and SUA. Finally, the recursive algorithm was used to calculate the inflection point in the nonlinear relationship, and the two-stage piecewise linear regression model was used to analyze the relationship between WWI and SUA on both sides of the inflection point. Results. In all the 6494 participants, through the fully adjusted model, this study found that there was a positive correlation between WWI and SUA (β = 5.64; 95% CI: 2.62 and 8.66). In addition, this positive correlation still had certain statistical significance in the subgroup analysis stratified by sex, age, and race. Our research team found a significant positive correlation between the WWI and SUA in females, but the correlation was not significant in males. We also found a small inverted U-shaped curve between the WWI and SUA in men when we stratified the sex subgroups. The small inflection point was determined to be 11.5 cm/√ kg. In racial subgroup analysis, we also found a U-shaped relationship between the WWI and SUA in non-Hispanic White and other race/ethnicity (the inflection point was 11.08 cm/√ kg and 12.14 cm/√ kg, respectively). Conclusion. This study showed that the WWI was a newly developed and new predictor of centripetal obesity independent of body weight and there was a positive correlation between the WWI and SUA.

Neural activity in the cortex is highly variable in response to repeated stimuli. Population recordings across the cortex demonstrate that the variability of neuronal responses is shared among large groups of neurons and concentrates in a low dimensional space. However, the source of the population-wide shared variability is unknown. In this work, we analyzed the dynamical regimes of spatially distributed networks of excitatory and inhibitory neurons. We found chaotic spatiotemporal dynamics in networks with similar excitatory and inhibitory projection widths, an anatomical feature of the cortex. The chaotic solutions contain broadband frequency power in rate variability and have distance-dependent and low-dimensional correlations, in agreement with experimental findings. In addition, rate chaos can be induced by globally correlated noisy inputs. These results suggest that spatiotemporal chaos in cortical networks can explain the shared variability observed in neuronal population responses.

Calcium phosphate cements (CPC) are widely anticipated to be an optimum bone repair substitute due to its satisfied biocompatibility and degradability, suitable to be used in minimally invasive treatment of bone defects. However the clinical application of CPC is still not satisfied by its poor cohesiveness and mechanical properties, in particular its osteoinductivity. Hyaluronic acid reinforced calcium phosphate cements (HA/CPC) showed extroadinary potential not only enhancing the compressive strength of the cements but also significantly increasing its osteoinductivity. In our study, the compressive strength of HA/CPC increased significantly when the cement was added 1% hyaluronic acid (denoted as 1-HA/CPC). In the meantime, hyaluronic acid obviously promoted ALP activity, osteogenic related protein and mRNA expression of hBMSCs (human bone marrow mesenchymal stem cells) in vitro, cement group of HA/CPC with 4% hyaluronic acid adding (denoted as 4-HA/CPC) showed optimal enhancement in hBMSCs differentiation. After being implanted in rat tibial defects, 4-HA/CPC group exhibited better bone repair ability and bone growth promoting factors, comparing to pure CPC and 1-HA/CPC groups. The underlying biological mechanism of this stimulation for HA/CPC may be on account of higher osteogenic promoting factors secretion and osteogenic genes expression with hyaluronic acid incorporation. These results indicate that hyaluronic acid is a highly anticipated additive to improve physicochemical properties and osteoinductivity performance of CPCs for minimally invasive healing of bone defects.

Abstract Objective Evidence linking total testosterone and bone mineral density (BMD) in adults is very limited. According to our review of the literature, only a few reports have focused on the relationship between total testosterone and bone mineral density in adults. Therefore, the purpose of this study was to determine the relationship between total testosterone and total bone mineral density in adults aged 40–60 years. Methods We used a cross-sectional study of a non-institutionalized U.S. population sample from the National Health and Nutrition Examination Survey. A weighted multivariate linear regression model was used to evaluate the relationship between total testosterone and total bone mineral density. Subgroup analyses were further performed. Results In multiple regression models adjusted for potential confounders, total testosterone levels were inversely associated with total bone mineral density. However, in the sex-stratified subgroup analysis, the association between total testosterone levels and total bone mineral density was not significant in female adolescents. There was no negative association between total testosterone and total BMD among men, adults 40 to 60 years of age, and other racial/ethnic groups. There is a negative association between total testosterone and total bone mineral density when total testosterone concentration is greater than 500 ng/dL among Non-Hispanic black. Conclusion Our statistical results show that the association between total testosterone levels and total bone mineral density varies by gender and race. Elevated total testosterone levels below 500 ng/dL have adverse effects on bone health. Total testosterone concentrations below 500 ng/dL may have no effect on bone health.

In this study, we describe the design, fabrication, and characterization of a cross-shaped structure reflective broadband THz polarization converter. The operating bandwidth of the proposed polarization converter was in the range of 0.8–1.6 THz. The polarization conversion rate (PCR) exceeded 85% in the frequency range of 1.07–1.35 THz and was as high as 91% at 1.35 THz. The cross PCR value exceeded 85% in the frequency range of 1.05–1.35 THz and reached a maximum value of 91%. The performance characteristics (bandwidth and PCR) of the proposed polarization converter were compared with those of similar previously reported devices, and the results indicated that the proposed polarization converter exhibits better performance. The proposed THz polarization converter is suitable for a wide range of applications in communication and polarization manipulation devices.

Nociceptors in the dorsal root ganglia (DRG) and trigeminal ganglia (TG) are necessary for transmitting pain and itch signals. However, the molecular mechanism regulating nociceptor development remains largely unknown. This study identifies that the transcription factor Meis1 is generally expressed in two groups of sensory neurons in the developing DRG. During prenatal and neonatal stages, approximately 2/3 of Meis1+ neurons are Runx1+ nociceptors, while 1/3 of Meis1+ neurons are NF200+ myelinated neurons. At postnatal stages, Meis1 expression in nociceptors is gradually reduced. Here, we constructed a Meis1 conditional knockout mouse line to selectively delete Meis1 in Nav1.8 lineage nociceptors. Microarray analyses showed that differentially expressed genes in the Meis1 mutant DRG were enriched in pathways related to sensory perception of pain and nervous system development. In addition, Meis1 regulates the expression of some marker genes of Nppb+ neurons and C-LTMRs. Furthermore, Meis1 mutant mice exhibit behavioral deficits in response to light mechanical pain, static touch and chemical itch. Therefore, this study reveals that Meis1 is required to regulate the development of nociceptors.

Diabetes-associated cognitive decline (DCD), is one of the complications of diabetes, which is characterized by a series of neurophysiological and pathological abnormalities. However, the exact pathogenesis of DCD is still unknown. Single-cell RNA sequencing (scRNA-seq) could discover unusual subpopulations, explore functional heterogeneity and identify signaling pathways and potential markers. The aim of this research was to provide deeper opinion into molecular and cellular changes underlying DCD, identify different cellular types of the diabetic mice hippocampus at single-cell level, and elucidate the factors mediating the pathogenesis of DCD. To elucidate cell specific gene expression changes in the hippocampus of diabetic encephalopathy. Single-cell RNA sequencing of hippocampus from db/m and db/db mice was carried out. Subclustering analysis was performed to further describe microglial cell subpopulations. Interestingly using immunohistochemistry, these findings were confirmed at the protein level. Single cell analysis yielded transcriptome data for 14621 hippocampal cells and defined 11 different cell types. Analysis of differentially expressed genes in the microglia compartments indicated that infection- and immune system process- associated terms, oxidative stress and inflammation play vital roles in the progression of DCD. Compared with db/m mouse, experiments at the protein level supported the activation of microglia, increased expression of inflammatory factors and oxidative stress damage in the hippocampus of db/db mouse. In addition, a major finding of our research was the subpopulation of microglia that express genes related to pro-inflammatory disease-associated microglia (DAM). Our research reveals pathological alterations of inflammation and oxidative stress mediated hippocampal damage in the db/db mice, and may provide potential diagnostic biomarkers and therapeutic interventions for DCD.

Improvements in perception are frequently accompanied by decreases in correlated variability in sensory cortex. This relationship is puzzling because overall changes in correlated variability should minimally affect optimal information coding. We hypothesize that this relationship arises because instead of using optimal strategies for decoding the specific stimuli at hand, observers prioritize generality: a single set of neuronal weights to decode any stimuli. We tested this using a combination of multineuron recordings in the visual cortex of behaving rhesus monkeys and a cortical circuit model. We found that general decoders optimized for broad rather than narrow sets of visual stimuli better matched the animals’ decoding strategy, and that their performance was more related to the magnitude of correlated variability. In conclusion, the inverse relationship between perceptual performance and correlated variability can be explained by observers using a general decoding strategy, capable of decoding neuronal responses to the variety of stimuli encountered in natural vision.

High-nitrogen stainless steel (HNSS) has been widely concerned and studied owing to its excellent mechanical, corrosion resistance, and biocompatibility properties. A series of HNSS was prepared by metal injection molding (MIM) using gas atomized Fe–Cr–Mn–Mo–0.3 N duplex stainless steel powders. Both sintering and solution treatments were carried out in an N2 atmosphere. The effects of nitrogen distribution and phase transformation on the mechanical properties of MIM HNSS during sintering and solution were studied. The results show that as the sintering temperature increased, the sample density increased, but the total nitrogen content decreased. Nitrogen and Cr2N concentration gradients along the cross-section of as-sintered samples were formed after cooling. The high nitrogen content promotes the decomposition of γ: γsaturated translated to γ and Cr2N. Meanwhile, the low Mn content in austenite also decomposes γ: γ translated to α and Cr2N. After solution treatment, a single γ phase was obtained for samples sintered at 1200 to 1320 °C. For solution treatment samples sintered at 1320 and 1350 °C, their tensile strength was 988.76 and 1036.12 MPa; yield strength was 615.61 and 636.14 MPa, and elongation was 42.58 and 40.08%, respectively. These values vastly exceeded the published MIM HNSS values.

There is a need for synthetic grafts to reconstruct large bone defects using minimal invasive surgery. Our previous study showed that incorporation of Sr into bioactive borate glass cement enhanced the osteogenic capacity in vivo. However, the amount of Sr in the cement to provide an optimal combination of physicochemical properties and capacity to stimulate bone regeneration and the underlying molecular mechanism of this stimulation is yet to be determined. In this study, bone cements composed of bioactive borosilicate glass particles substituted with varying amounts of Sr (0 mol% to 12 mol% SrO) were created and evaluated in vitro and in vivo. The setting time of the cement increased with Sr substitution of the glass. Upon immersion in PBS, the cement degraded and converted more slowly to HA (hydroxyapatite) with increasing Sr substitution. The released Sr2+ modulated the proliferation, differentiation, and mineralization of hBMSCs (human bone marrow mesenchymal stem cells) in vitro. Osteogenic characteristics were optimally enhanced with cement (designated BG6Sr) composed of particles substituted with 6mol% SrO. When implanted in rabbit femoral condyle defects, BG6Sr cement supported better peri-implant bone formation and bone-implant contact, comparing to cements substituted with 0mol% or 9mol% SrO. The underlying mechanism is involved in the activation of Wnt/β-catenin signaling pathway in osteogenic differentiation of hBMSCs. These results indicate that BG6Sr cement has a promising combination of physicochemical properties and biological performance for minimally invasive healing of bone defects.

Mutations in the human N-glycanase 1 (NGLY1) cause a rare, multisystem congenital disorder with global developmental delay. However, the mechanisms by which NGLY1 and its homologs regulate embryonic development are not known. Here we show that Drosophila Pngl encodes an N-glycanase and exhibits a high degree of functional conservation with human NGLY1. Loss of Pngl results in developmental midgut defects reminiscent of midgut-specific loss of BMP signaling. Pngl mutant larvae also exhibit a severe midgut clearance defect, which cannot be fully explained by impaired BMP signaling. Genetic experiments indicate that Pngl is primarily required in the mesoderm during Drosophila development. Loss of Pngl results in a severe decrease in the level of Dpp homodimers and abolishes BMP autoregulation in the visceral mesoderm mediated by Dpp and Tkv homodimers. Thus, our studies uncover a novel mechanism for the tissue-specific regulation of an evolutionarily conserved signaling pathway by an N-glycanase enzyme.

Itch, a sensation eliciting a desire to scratch, is distinct from but not completely independent of pain. Inspiring achievements have been made in the characterization of itch-related receptors and neurotransmitters, but the molecular mechanisms controlling the development of pruriceptors remain poorly understood. Here, our RNAseq and in situ hybridization data show that the transcription factor Tlx3 is required for the expression of a majority of itch-related molecules in the dorsal root ganglion (DRG). As a result, Tlx3F/F;Nav1.8-cre mice exhibit significantly attenuated acute and dry skin-induced chronic itch. Furthermore, our study indicates that TRPV1 plays a pivotal role in the chronic itch evoked by dry skin and allergic contact dermatitis (ACD). The mutants also display impaired response to cold and inflammatory pain and elevated response to capsaicin, whereas the responses to acute mechanical, thermal stimuli and neuropathic pain remain normal. In Tlx3F/F;Nav1.8-cre mice, TRPV1 is derepressed and expands predominantly into IB4+ non-peptidergic (NP) neurons. Collectively, our data reveal a molecular mechanism in regulating the development of pruriceptors and controlling itch and pain sensations.

The cytoplasmic peptide:N-glycanase (Ngly1 in mammals) is a de-N-glycosylating enzyme that is highly conserved among eukaryotes. It was recently reported that subjects harboring mutations in the NGLY1 gene exhibited severe systemic symptoms (NGLY1-deficiency). While the enzyme obviously has a critical role in mammals, its precise function remains unclear. In this study, we analyzed Ngly1-deficient mice and found that they are embryonic lethal in C57BL/6 background. Surprisingly, the additional deletion of the gene encoding endo-β-N-acetylglucosaminidase (Engase), which is another de-N-glycosylating enzyme but leaves a single GlcNAc at glycosylated Asn residues, resulted in the partial rescue of the lethality of the Ngly1-deficient mice. Additionally, we also found that a change in the genetic background of C57BL/6 mice, produced by crossing the mice with an outbred mouse strain (ICR) could partially rescue the embryonic lethality of Ngly1-deficient mice. Viable Ngly1-deficient mice in a C57BL/6 and ICR mixed background, however, showed a very severe phenotype reminiscent of the symptoms of NGLY1-deficiency subjects. Again, many of those defects were strongly suppressed by the additional deletion of Engase in the C57BL/6 and ICR mixed background. The defects observed in Ngly1/Engase-deficient mice (C57BL/6 background) and Ngly1-deficient mice (C57BL/6 and ICR mixed background) closely resembled some of the symptoms of patients with an NGLY1-deficiency. These observations strongly suggest that the Ngly1- or Ngly1/Engase-deficient mice could serve as a valuable animal model for studies related to the pathogenesis of the NGLY1-deficiency, and that cytoplasmic ENGase represents one of the potential therapeutic targets for this genetic disorder.

At embryonic stages, Olig3 is initially expressed in the dorsal-most region of the spinal cord, but later in the ventral marginal zone as well. Previous studies indicated that Olig3 controlled the patterning of dorsal spinal cord and loss of Olig3 function led to the re-specification of dI2 and dI3 neurons into dI4 interneurons. However, the role of Olig3 in regulating the development of ventral spinal cord has remained unknown. BrdU labeling demonstrated that ventral Olig3 was expressed in the post-mitotic neurons and Olig3+ cells seen at late embryonic stages were born at the earlier stage but remained in the marginal zone throughout embryogenesis. Loss-of-function and gain-of-function experiment indicated that Nkx2.2 regulated the expression of Olig3 in V3 interneurons. However, Olig3 mutation didn't apparently affect the generation and migration of ventral neurons. These findings suggest that Olig3 plays different roles in regulating the development of dorsal and ventral spinal cord.