Gate-Tunable Positive and Negative Photoconductance in Near-Infrared Organic Heterostructures for In-Sensor Computing.

The rapid growth of sensor data in the artificial intelligence often causes significant reductions in processing speed and power efficiency. Addressing this challenge, in-sensor computing is introduced as an advanced sensor architecture that simultaneously senses, memorizes, and processes images at the sensor level. However, this is rarely reported for organic semiconductors that possess inherent flexibility and tunable bandgap. Herein, an organic heterostructure that exhibits a robust photoresponse to near-infrared (NIR) light is introduced, making it ideal for in-sensor computing applications. This heterostructure, consisting of partially overlapping p-type and n-type organic thin films, is compatible with conventional photolithography techniques, allowing for high integration density of up to 520 devices cm-2 with a 5 µm channel length. Importantly, by modulating gate voltage, both positive and negative photoresponses to NIR light (1050 nm) are attained, which establishes a linear correlation between responsivity and gate voltage and consequently enables real-time matrix multiplication within the sensor. As a result, this organic heterostructure facilitates efficient and precise NIR in-sensor computing, including image processing and nondestructive reading and classification, achieving a recognition accuracy of 97.06%. This work serves as a foundation for the development of reconfigurable and multifunctional NIR neuromorphic vision systems.

Mendelian randomization analysis reveals causal associations of serum metabolites with sepsis and 28-day mortality.

Metabolic disorder has been found to be an important factor in the pathogenesis and progression of sepsis. However, the causation of such an association between serum metabolites and sepsis has not been established. We conducted a two-sample Mendelian randomization (MR) study. A genome-wide association study of 486 human serum metabolites was used as the exposure, whereas sepsis and sepsis mortality within 28 days were set as the outcomes. In MR analysis, 6 serum metabolites were identified to be associated with an increased risk of sepsis, and 6 serum metabolites were found to be related to a reduced risk of sepsis. Furthermore, there were 9 metabolites positively associated with sepsis-related mortality, and 8 metabolites were negatively correlated with sepsis mortality. In addition, "glycolysis/gluconeogenesis" (p = 0.001), and "pyruvate metabolism" (p = 0.042) two metabolic pathways were associated with the incidence of sepsis. This MR study suggested that serum metabolites played significant roles in the pathogenesis of sepsis, which may provide helpful biomarkers for early disease diagnosis, therapeutic interventions, and prognostic assessments for sepsis.

Raman lidar at 355 nm using low dead time photon counting for atmospheric aerosol measurements.

Photon counting is an effective way to enhance the dynamic range of the data acquisition system (DAQ) in Raman lidars. However, there exists a deficiency of relatively high dead times among current options, which necessitates an additional calibration procedure for the nonlinearity of the photon counting signal, thus leading to unanticipated errors. A field programmable gate array (FPGA)-based photon counting module has been proposed and implemented in a Raman lidar, offering two operational channels. Through observational experiments, it was determined that this module has an overall dead time of 1.13 ns taking advantage of the high-speed amplifier/discriminator pair and the logic design, a significant improvement compared to the 4.35 ns of a commercially used Licel transient recorder within the same counting rate range. This notably low dead time implies that its output maintains sufficient linearity even at substantially high counting rates. As a result, the need for a dead time calibration procedure prior to signal integration with the analog signal is eliminated, reducing uncertainty in the final integrated signal, and even in the retrieval result. The backscattering result of the comparison between this module and a transient recorder indicates that a more precise performance can be acquired benefiting from this hardware upgrading.

Altered cortical thickness-based structural covariance networks in type 2 diabetes mellitus.

Cognitive impairment is a common complication of type 2 diabetes mellitus (T2DM), and early cognitive dysfunction may be associated with abnormal changes in the cerebral cortex. This retrospective study aimed to investigate the cortical thickness-based structural topological network changes in T2DM patients without mild cognitive impairment (MCI). Fifty-six T2DM patients and 59 healthy controls underwent neuropsychological assessments and sagittal 3-dimensional T1-weighted structural magnetic resonance imaging. Then, we combined cortical thickness-based assessments with graph theoretical analysis to explore the abnormalities in structural covariance networks in T2DM patients. Correlation analyses were performed to investigate the relationship between the altered topological parameters and cognitive/clinical variables. T2DM patients exhibited significantly lower clustering coefficient (C) and local efficiency (Elocal) values and showed nodal property disorders in the occipital cortical, inferior temporal, and inferior frontal regions, the precuneus, and the precentral and insular gyri. Moreover, the structural topological network changes in multiple nodes were correlated with the findings of neuropsychological tests in T2DM patients. Thus, while T2DM patients without MCI showed a relatively normal global network, the local topological organization of the structural network was disordered. Moreover, the impaired ventral visual pathway may be involved in the neural mechanism of visual cognitive impairment in T2DM patients. This study enriched the characteristics of gray matter structure changes in early cognitive dysfunction in T2DM patients.

Toward High-Performance Mg/S Batteries with M4-Assisted Mg(AlCl4 )2 /PYR14TFSI/DME Electrolyte and MoS2 @CMK/S Cathode.

Rechargeable magnesium batteries (RMBs) are considered as one of the most promising candidates for next-generation batteries. However, the popularization of RMBs is seriously plagued due to the lack of suitable non-nucleophilic electrolytes and the passivation of Mg anode. Herein, a novel non-nucleophilic electrolyte is developed by introducing (s)-1-methoxy-2-propylamine (M4) into themagnesium aluminum chloride complex (MACC)-like electrolyte. The as-synthesizes Mg(AlCl4 )2 -IL-DME-M4 electrolyte enables robust reversible cycling of Mg plating/stripping with low overpotential, high anodic stability, and ionic conductivity (8.56 mS cm-1 ). These features should be mainly attributed to the in situ formation of an MgF2 containing Mg2+ -conducting interphase, which dramatically suppresses the passivation and parasitic reaction of Mg anode with electrolyte. Remarkably, the Mg/S batteries assemble with as-synthesize electrolyte and a new type MoS2 @CMK/S cathode deliver unprecedented electrochemical performance. Specifically, the Mg/S battery exhibited the highest reversible capacity up to 1210 mAh g-1 at 0.1 C, excellent rate capability and satisfactory long-term cycling stability with a reversible capacity of 370 mAh g-1 (coulombic efficiency of ≈100%) at 1.0 C for 600 cycles. The study findings provide a novel strategy and inspiration for designing efficient non-nucleophilic Mg electrolyte and suitable sulfur-host materials for practical Mg/S battery applications.

Discriminative patterns of traditional Chinese medicine in the non-interventional treatment of malignant lung tumors based on real-world data analysis / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：基于临床病历信息系统，采用数据挖掘方法从真实世界角度分析中医药非介入治疗肺恶性肿瘤的辨治规律。方法：收集2015年1月1日至2021年12月31日北京中医药大学东直门医院病历系统中诊断为肺恶性肿瘤的患者病史、刻下症和用药信息，在剔除使用介入治疗手段的病例后建立数据库。采用Microsoft Office Excel 2019对高频药物的频数、四气五味、归经及功效进行描述性统计，并对病史和刻下症反映的症状进行数据化统计；对统计得到的高频药物和症状信息借助SPSS Modeler 18.0软件中Apriori算法对核心数据进行关联规则分析，并用Web节点构建关联网状图；借助SPSS Stastistics 23.0进行聚类分析。结果：共纳入119例未进行介入治疗的肺恶性肿瘤患者，中医常见症状为咳嗽、白痰、喘憋、纳差、眠差、痰黏、便秘、乏力、胸闷、气短；药物四气以温药最多；五味以甘味最多；归经以肺经频率最高。关联规则结果显示，二项支持度最高的组合为半夏→柴胡、半夏→瓜蒌、杏仁→麻黄；三项关联支持度最高的组合为半夏→茯苓、柴胡，杏仁→麻黄、半夏，半夏→杏仁、柴胡，半夏→瓜蒌、贝母。聚类结果聚为3类，依次为肺阴虚证、痰热壅肺证和肺气虚证。结论：中医药非介入治疗肺恶性肿瘤的中医药辨治规律为：聚类证型依次为肺阴虚证、痰热壅肺证和肺气虚证。治疗多用和解少阳、行气止咳平喘和清虚热化痰饮为主，药物以半夏、甘草、黄芩、茯苓、柴胡多见。

Regulating Lewis Acidic Sites of 1T-2H MoS2 Catalysts for Solar-Driven Photothermal Catalytic H2 Production from Lignocellulosic Biomass.

Solar-driven photothermal catalytic H2 production from lignocellulosic biomass was achieved by using 1T-2H MoS2 with tunable Lewis acidic sites as catalysts in an alkaline aqueous solution, in which the number of Lewis acidic sites derived from the exposed Mo edges of MoS2 was successfully regulated by both the formation of an edge-terminated 1T-2H phase structure and tunable layer number. Owing to the abundant Lewis acidic sites for the oxygenolysis of lignocellulosic biomass, the 1T-2H MoS2 catalyst shows high photothermal catalytic lignocellulosic biomass-to-H2 transformation performance in polar wood chips, bamboo, rice straw corncobs, and rice hull aqueous solutions, and the highest H2 generation rate and solar-to-H2 (STH) efficiency respectively achieves 3661 µmol·h-1·g-1 and 0.18% in the polar wood chip system under 300 W Xe lamp illumination. This study provides a sustainable and cost-effective method for the direct transformation of renewable lignocellulosic biomass to H2 fuel driven by solar energy.

Carbon price prediction based on multiple decomposition and XGBoost algorithm.

Carbon trading is an effective way to limit global carbon dioxide emissions. The carbon pricing mechanisms play an essential role in the decision of the market participants and policymakers. This study proposes a carbon price prediction model, multi-decomposition-XGBOOST, which is based on sample entropy and a new multiple decomposition algorithm. The main steps of the proposed model are as follows: (1) decompose the price series into multiple intrinsic mode functions (IMFs) by using complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN); (2) decompose the IMF with the highest sample entropy by variational mode decomposition (VMD); (3) select and recombine some IMFs based on their sample entropy, and then perform another round of decomposition via CEEMDAN; (4) predict IMFs by XGBoost model and sum up the prediction results. The model has exhibited reliable predictive performance in both the highly fluctuating Beijing carbon market and the comparatively stable Hubei carbon market. The proposed model in Beijing carbon market achieves improvements of 30.437%, 44.543%, and 42.895% in RMSE, MAE, and MAPE, when compared to the single XGBoost models. Similarly, in Hubei carbon market, the RMSE, MAE, and MAPE based on multi-decomposition-XGBOOST model decreased by 28.504%, 39.356%, and 39.394%. The findings indicate that the proposed model has better predictive performance for both volatile and stable carbon prices.

CRISPR/Cas12a combined with RPA for detection of T. gondii in mouse whole blood.

BACKGROUND: Toxoplasma gondii is an opportunistic protozoan that is ubiquitous in humans and animals. It can invade any human organ and cause severe diseases, including toxoplasma ophthalmopathy, meningoencephalitis, and liver necrosis. Porcine toxoplasmosis is prevalent in China. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and Cas (CRISPR-Associated Protein) systems are widely used for gene editing and pathogen detection. CRISPR-based diagnostics are molecular assays that have been developed to detect parasites with high sensitivity and specificity. METHODS: This study aimed to establish a combined CRISPR/Cas12a and RPA rapid detection method for T. gondii by targeting the B1 gene and 529 bp repeat element (529 RE). The detection results could be visualized by the fluorescence or lateral flow strips (LFS). The sensitivity and specificity of the method were evaluated, and T. gondii-infected mouse blood was used for detection. RESULTS: The results indicated that the established method for T. gondii detection was satisfactory, with a detection limit of 1.5 cp/µl for the two loci. Moreover, the B1 gene could detect 1 tachyzoite per reaction, and the 529 RE could detect 0.1 tachyzoite per reaction, consistently with the highly sensitive nested polymerase chain reaction (PCR) results. The method was suitable for strains, including RH, and did not cross-react with other protozoa DNA with similar habits. The T. gondii-infected mouse blood samples were all positive for T. gondii at 1, 3, and 5 days post infection (dpi). CONCLUSIONS: This study established a rapid, sensitive, and time-saving DNA detection method for T. gondii that has the potential to be an alternative tool for T. gondii detection in the field.

The role of apoptosis in the pathogenesis of osteoarthritis.

PURPOSE: Apoptosis is an important physiological process, making a great difference to development and tissue homeostasis. Osteoarthritis (OA) is a chronic joint disease characterized by degeneration and destruction of articular cartilage and bone hyperplasia. This purpose of this study is to provide an updated review of the role of apoptosis in the pathogenesis of osteoarthritis. METHODS: A comprehensive review of the literature on osteoarthritis and apoptosis was performed, which mainly focused on the regulatory factors and signaling pathways associated with chondrocyte apoptosis in osteoarthritis and other pathogenic mechanisms involved in chondrocyte apoptosis. RESULTS: Inflammatory mediators such as reactive oxygen species (ROS), nitric oxide (NO), IL-1ß, tumor necrosis factor-α (TNF-α), and Fas are closely related to chondrocyte apoptosis. NF-κB signaling pathway, Wnt signaling pathway, and Notch signaling pathway activate proteins and gene targets that promote or inhibit the progression of osteoarthritis disease, including chondrocyte apoptosis and ECM degradation. Long non-coding RNAs (LncRNAs) and microRNAs (microRNAs) have gradually replaced single and localized research methods and become the main research approaches. In addition, the relationship between cellular senescence, autophagy, and apoptosis was also briefly explained. CONCLUSION: This review offers a better molecular delineation of apoptotic processes that may help in designing new therapeutic options for OA treatment.

Chromatic aberration correction based on cross-channel information alignment in microscopy.

A microscope usually consists of dozens of complex lenses and requires careful assembly, alignment, and testing before use. Chromatic aberration correction is a significant step in the design of microscopes. Reducing chromatic aberration by improving optical design will inevitably increase the overall weight and size of the microscope, leading to more cost in manufacturing and maintenance. Nevertheless, the improvement in hardware can only achieve limited correction. In this paper, we propose an algorithm based on cross-channel information alignment to shift some of the correction tasks from optical design to post-processing. Additionally, a quantitative framework is established to evaluate the performance of the chromatic aberration algorithm. Our algorithm outperforms the other state-of-the-art methods in both visual appearance and objective assessments. The results indicate that the proposed algorithm can effectively obtain higher-quality images without changing the hardware or engaging the optical parameters.

Inhibiting virus replication and excessive inflammatory response: Mechanism of combined prescription of Ma-Xing-Shi-Gan decoction and Xiao-Chai-Hu decoction against influenza virus.

ETHNOPHARMACOLOGICAL RELEVANCE: The combined prescription of two classical decoctions (Ma-Xing-Shi-Gan decoction with Xiao-Chai-Hu decoction), named as San-Yang-He-Zhi (SYHZ) decoction, has been widely used for the treatment of influenza virus (IFV) infections for decades. AIM OF THE STUDY: This study aimed to evaluate the anti-influenza effect of SYHZ decoction and explore the underlying mechanism. MATERIALS AND METHODS: The ingredients of SYHZ decoction were analyzed by mass spectrometry. An animal model of IFV infection was established by challenging C57BL/6J mice with PR8 virus. Three groups of mice were infected with lethal or non-lethal doses of IFV, then followed by oral administration of phosphate-buffered saline (PBS), or SYHZ, or oseltamir; blank control mice (without IFV infection) were treated with PBS. Survival rate, Lung index, colon length, body weight loss and IFV viral load were measured 7 days post infection; histology and electron-microscopy examinations of lung tissue were performed; cytokine and chemokine levels in lung and serum were measured; and the intestinal metagenome, the cecum metabolome, and the lung transcriptome were analyzed. RESULTS: SYHZ treatment significantly improved survival rate compared with PBS (40% vs 0%); improved lung index, colon length, and body weight loss; and alleviated lung histological damage and viral load. SYHZ-treated mice had significantly lower levels of IL-1ß, TNF-α, IL-6, CCL2, CXCL10 in lung and serum, and increased levels of multiple bioactive components in cecum. Pro-inflammatory cytokines, Toll- and NOD-like receptors, pro-apoptosis molecules, and lung-injury-related proteins were downregulated in SYHZ mice, whereas surfactant protein and mucin were upregulated. The NOD-like receptor pathway, Toll-like receptor pathway, and NF-κB pathway were downregulated by SYHZ treatment. CONCLUSIONS: SYHZ decoction alleviated IFV infection in a mouse model. Multiple bioactive ingredients of SYHZ may inhibit replication of IFV and suppress excessive immune response.

Baicalin ameliorates multidrug-resistant Pseudomonas aeruginosa induced pulmonary inflammation in rat via arginine biosynthesis.

Multidrug-resistance (MDR) Pseudomonas aeruginosa (P. aeruginosa) is a lethal gram-negative pathogen causing hospital-acquired and ventilator-associated pneumonia, which is difficult to treat. Our previous studies confirmed that baicalin, an essential bioactive component in Scutellaria baicalensis Georgi, exhibited anti-inflammatory effects in an acute pneumonia rat model induced by MDR P. aeruginosa. However, this effect of baicalin in constrast its low bioavailability, and its mechanism of action is still unknown. Thus, this study investigated whether the therapeutic effects of baicalin against MDR P. aeruginosa acute pneumonia are owing to the regulation of gut microbiota and their metabolites using pyrosequencing of the 16S rRNA genes in rat feces and metabolomics. As a result, baicalin attenuated the inflammation by acting directly on neutrophils and regulated the production of the inflammatory cytokines TNF-α, IL-1ß, IL-6, and IL-10. The mechanisms were through down-regulation of TLR4 and inhibition of NF-κB. Furthermore, pyrosequencing of the 16S rRNA genes in rat feces revealed that baicalin regulated the composition of gut microbial communities. At the genus level, baicalin efficiently increased the abundance of Ligilactobacillus, Lactobacillus and Bacteroides, but decreased the abundance of Muribaculaceae and Alistipes. Further, arginine biosynthesis was analyzed as the core pathway regulated by baicalin via combination with predicting gut microbiota function and targeted metabolomics. In conclusion, this study has demonstrated that baicalin relieved inflammatory injury in acute pneumonia rat induced by MDR P. aeruginosa via arginine biosynthesis associated with gut microbiota. Baicalin could be a promising and effective adjunctive therapy for lung inflammation caused by MDR P. aeruginosa infection.

Berberine Ameliorates Abnormal Lipid Metabolism via the Adenosine Monophosphate-Activated Protein Kinase/Sirtuin 1 Pathway in Alcohol-Related Liver Disease.

Alcoholic fatty liver disease (AFLD) is an early stage of alcohol-related liver disease characterized by abnormal lipid metabolism in hepatocytes. To date, to our knowledge, there have been no effective strategies for preventing or treating alcohol-related liver disease besides alcohol abstinence. Berberine (BBR) is the main bioactive ingredient extracted from traditional Chinese medicines, such as Coptis and Scutellaria, which protect liver function and relieve liver steatosis. However, the potential role of BBR in AFLD remains unclear. Therefore, this study investigated the protective effects of BBR against Gao-binge model-induced AFLD in 6- to 8-week-old C57BL/6J male mice in vivo and ethyl alcohol (EtOH)-induced alpha mouse liver 12 (AML-12) cells in vitro. The results showed that BBR (200 mg/kg) attenuated alcoholic liver injury and suppressed lipid accumulation and metabolism disorders in vivo. Consistently, BBR effectively inhibited the expression of sterol regulatory element-binding transcription factor 1C, sterol regulatory element-binding transcription factor 2, fatty acid synthase, and 3-hydroxy-3-methylglutaryl-CoenzymeA reductase in EtOH-stimulated AML-12 cells in vitro and promoted the expression of sirtuin 1 (SIRT1) in EtOH-fed mice and EtOH-treated AML-12 cells. Furthermore, SIRT1 silencing attenuated the hepatic steatosis alleviation potential of BBR treatment. Mechanistically, molecular docking revealed the binding effect of BBR and adenosine monophosphate-activated protein kinase (AMPK). The results of further studies showed that a decrease in AMPK activity was accompanied by a significant inhibition of SIRT1 expression. SIRT1 silencing attenuated the protective effect of BBR, whereas the inhibition of its expression had no apparent effect on AMPK phosphorylation, suggesting that SIRT1 acts downstream of AMPK in AFLD. Collectively, BBR ameliorated abnormal lipid metabolism and alleviated EtOH-induced liver injury via the AMPK/SIRT1 pathway in AFLD mice.

BRD4 promotes hepatic stellate cells activation and hepatic fibrosis via mediating P300/H3K27ac/PLK1 axis.

Hepatic fibrosis (HF) is a reversible wound-healing response characterized by excessive extracellular matrix (ECM) deposition and secondary to persistent chronic injury. Bromodomain protein 4 (BRD4) commonly functions as a "reader" to regulate epigenetic modifications involved in various biological and pathological events, but the mechanism of HF remains unclear. In this study, we established a CCl4-induced HF model and spontaneous recovery model in mice and found aberrant BRD4 expression, which was consistent with the results in human hepatic stellate cells (HSCs)- LX2 cells in vitro. Subsequently, we found that distriction and inhibition of BRD4 restrained TGFß-induced trans-differentiation of LX2 cells into activated, proliferative myofibroblasts and accelerated apoptosis, and BRD4 overexpression blocked MDI-induced LX2 cells inactivation and promoted the proliferation and inhibited apoptosis of inactivated cells. Additionally, adeno-associated virus serotype 8-loaded short hairpin RNA-mediated BRD4 knockdown in mice significantly attenuated CCl4-induced fibrotic responses including HSCs activation and collagen deposition. Mechanistically, BRD4 deficiency inhibited PLK1 expression in activated LX2 cells, and ChIP and Co-IP assays revealed that BRD4 regulation of PLK1 was dependent on P300-mediated acetylation modification for H3K27 on the PLK1 promoter. In conclusion, BRD4 deficiency in the liver alleviates CCl4-induced HF in mice, and BRD4 participates in the activation and reversal of HSCs through positively regulating the P300/H3K27ac/PLK1 axis, providing a potential insight for HF therapy.

Pharmacological Mechanism of Sancao Yuyang Decoction in the Treatment of Oral Mucositis Based on Network Pharmacology and Experimental Validation.

Purpose: The network pharmacology analysis, molecular docking and experimental verification were performed to explore the pharmacological mechanisms of Sancao Yuyang Decoction (SCYYD) in the treatment of oral mucositis (OM). Methods: Active ingredients in SCYYD and their potential targets, as well as OM-related targets were screened from public databases. The core targets and signaling pathways of SCYYD against OM were determined by protein-protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The ingredient-target-disease network and target-pathway network were constructed. Subsequently, molecular docking was carried out to predict the binding activity between active ingredients and key targets. Moreover, in vivo experiment was conducted to further verify the core targets predicted by network pharmacology analysis. Results: A total of 119 bioactive ingredients were screened from the corresponding databases. One hundred and eighty-six putative targets were retrieved and bioinformatics analysis was performed to reveal the top 5 potential candidate agents and 10 core targets. GO and KEGG enrichment analysis showed that SCYYD exerted excellent therapeutic effects on OM through several pathways, such as HIF-1 and Ras signaling pathway. Subsequently, molecular docking showed that main ingredients in SCYYD had optimal binding activities to the key protein targets. Moreover, the result of in vivo experiment indicated that SCYYD not only inhibited inflammation response and promoted wound healing of oral mucosa in OM rats, but also reversed high expressions of SRC, HSP90AA1, STAT3, HIF1α, mTOR, TLR4, MMP9, and low expression of ESR1. Conclusion: This study preliminarily uncovered the multiple compounds and multiple targets of SCYYD against OM using network pharmacology, molecular docking and in vivo verification, which provided a new insight of the pharmacological mechanisms of SCYYD in treatment of OM.

Promotion effect of TGF-β-Zfp423-ApoD pathway on lip sensory recovery after nerve sacrifice caused by nerve collateral compensation / 国际口腔科学杂志·英文版

Resection of oral and maxillofacial tumors is often accompanied by the inferior alveolar nerve neurectomy, resulting in abnormal sensation in lower lip. It is generally believed that spontaneous sensory recovery in this nerve injury is difficult. However, during our follow-up, patients with inferior alveolar nerve sacrifice showed different degrees of lower lip sensory recovery. In this study, a prospective cohort study was conducted to demonstrate this phenomenon and analyze the factors influencing sensory recovery. A mental nerve transection model of Thy1-YFP mice and tissue clearing technique were used to explore possible mechanisms in this process. Gene silencing and overexpression experiments were then conducted to detect the changes in cell morphology and molecular markers. In our follow-up, 75% of patients with unilateral inferior alveolar nerve neurectomy had complete sensory recovery of the lower lip 12 months postoperatively. Patients with younger age, malignant tumors, and preservation of ipsilateral buccal and lingual nerves had a shorter recovery time. The buccal nerve collateral sprouting compensation was observed in the lower lip tissue of Thy1-YFP mice. ApoD was demonstrated to be involved in axon growth and peripheral nerve sensory recovery in the animal model. TGF-β inhibited the expression of STAT3 and the transcription of ApoD in Schwann cells through Zfp423. Overall, after sacrificing the inferior alveolar nerve, the collateral compensation of the ipsilateral buccal nerve could innervate the sensation. And this process was regulated by TGF-β-Zfp423-ApoD pathway.

Circular RNA hsa_circ_0051246 acts as a microRNA-375 sponge to promote the progression of gastric cancer stem cells via YAP1.

Background: Gastric cancer (GC) stem cells play an important role in GC progression. Circular RNAs (circRNAs) act as microRNA (miRNA) sponges and inhibit the biological function of miRNAs in GC cytoplasm. MiRNAs also participate in GC progress. circ_0051246 was shown to be associated with miR-375 after analyzing GC microarray data GSE78091 and GSE83521. The oncoprotein Yes-associated protein 1 (YAP1) is targeted by miR-375 and can be inactivated via the Hippo tumor suppressor pathway. Due to insufficient research on circ_0051246, this study aimed to investigate its relationship with miR-375 and YAP1 in cancer stem cells (CSCs). Methods: SGC-7901 CSCs were used to establish knockdown/overexpression models of circ_0051246, miR-375, and YAP1. Malignant phenotypes of CSCs were assessed using Cell Counting Kit 8, colony/sphere formation, 5-Ethynyl-2'-deoxyuridine assay, flow cytometry, Transwell, and wound healing assays. To detect the interactions between circ_0051246, miR-375, and YAP1 in CSCs, a dual-luciferase reporter assay and fluorescence in situ hybridization were performed. In addition, 24 BALB/c nude mice were used to establish orthotopic xenograft tumor models. Four groups of mice were injected with CSCs (1 × 106 cells/100 µL) with circ_0051246 knockdown, miR-375 overexpression, or their respective control cells, and tumor progression and gene expression were observed by hematoxylin-eosin staining, immunohistochemistry. Western blot and quantitative real-time PCR were utilized to examine protein and gene expression, respectively. Results: Circ_0051246 silencing reduced viability, promoted apoptosis, and inhibited proliferation, migration and invasion of CSCs. The functional effects of miR-375 mimics were comparable to those of circ_0051246 knockdown; however, the opposite was observed after miR-375 inhibitors treatment of CSCs. Furthermore, circ_0051246-overexpression antagonized the miR-375 mimics' effects on CSCs. Additionally, YAP1 overexpression promoted CSC features, such as self-renewal, migration, and invasion, inhibited apoptosis and E-cadherin levels, and upregulated the expression of N-cadherin, vimentin, YAP1, neurogenic locus notch homolog protein 1, and jagged canonical notch ligand 1. Conversely, YAP1-silenced produced the opposite effect. Moreover, miR-375 treatment antagonized the malignant effects of YAP1 overexpression in CSCs. Importantly, circ_0051246 knockdown and miR-375 activation suppressed CSC tumorigenicity in vivo. Conclusion: This study highlights the promotion of circ_0051246-miR-375-YAP1 axis activation in GC progression and provides a scientific basis for research on the molecular mechanism of CSCs.

Altered functional hubs and connectivity in type 2 diabetes mellitus with and without mild cognitive impairment.

Cognitive impairment in type 2 diabetes mellitus (T2DM) is associated with functional and structural abnormalities of brain networks, especially the damage to hub nodes in networks. This study explored the abnormal hub nodes of brain functional networks in patients with T2DM under different cognitive states. Sixty-five patients with T2DM and 34 healthy controls (HCs) underwent neuropsychological assessment. Then, degree centrality (DC) analysis and seed-based functional connectivity (FC) analysis were performed to identify the abnormal hub nodes and the FC patterns of these hubs in T2DM patients with mild cognitive impairment (MCI) (DMCI group, N = 31) and without MCI (DMCN group, N = 34). Correlation analyzes examined the relationship between abnormal DC and FC and clinical/cognitive variables. Compared with HCs, both T2DM groups showed decreased DC values in the visual cortex, and the T2DM patients with MCI (DMCI) showed more extensive alterations in the right parahippocampal gyrus (PHG), bilateral posterior cingulate cortex (PCC), and left superior frontal gyrus (SFG) regions than T2DM patients with normal cognitive function. Seed-based FC analysis of PHG and PCC nodes showed that functional disconnection mainly occurred in visual and memory connectivity in patients with DMCI. Multiple abnormal DC values correlated with neuropsychological tests in patients with T2DM. In conclusion, this study found that the DMCI group displayed more extensive alterations in hub nodes and FC in vision and memory-related brain regions, suggesting that visual-related regions dysfunctions and disconnection may be involved in the neuropathology of visuospatial function impairment in patients with DMCI.