Selection strategy for endoscopic necrosectomy approaches of infected walled-off pancreatic necrosis: Analysis of 101 patients from a single center with long-term follow-up.

OBJECTIVES: Endoscopic necrosectomy (EN) is a promising minimally invasive approach for treating infected walled-off pancreatic necrosis (WOPN). Multiple EN approaches are currently available, though criteria for selecting the optimal approaches are lacking. We aimed to propose a rational selection strategy of EN and to retrospectively evaluate its safety and effectiveness. METHODS: Altogether 101 patients who underwent EN for infected WOPN at a tertiary hospital between June 2009 and February 2023 were retrospectively included for analysis. Demographic characteristics, details of the EN procedures, procedure-related adverse events, and clinical outcomes were investigated. RESULTS: Among these 101 patients with WOPN, 56 (55.4%) underwent transluminal EN, 38 (37.6%) underwent percutaneous EN, and seven (6.9%) underwent combined approach, respectively. Clinical success was achieved in 94 (93.1%) patients. Seven (6.9%) experienced procedure-related adverse events, and seven (6.9%) died during the treatment period. During a median follow-up of 50 months, 5 (5.3%) of the 94 patients had disease recurrence, 17.0% (16/94) had new-onset diabetes mellitus, and 6.4% (6/94) needed oral pancreatic enzyme supplementation. The clinical success rate, procedure-related adverse event rate, and long-term follow-up outcomes were not significantly different among the three groups. High APACHE-II scores (≥15) and organ failure were identified as factors related to treatment failure. CONCLUSIONS: A selection strategy for EN approaches, based on the extent of necrosis and its distance from the gastrointestinal lumen (using a threshold of 15 mm), is safe and effective for treating infected WOPN in both short-term and long-term outcomes.

Sortilin-mediated translocation of mitochondrial ACSL1 impairs adipocyte thermogenesis and energy expenditure in male mice.

Beige fat activation involves a fuel switch to fatty acid oxidation following chronic cold adaptation. Mitochondrial acyl-CoA synthetase long-chain family member 1 (ACSL1) localizes in the mitochondria and plays a key role in fatty acid oxidation; however, the regulatory mechanism of the subcellular localization remains poorly understood. Here, we identify an endosomal trafficking component sortilin (encoded by Sort1) in adipose tissues that shows dynamic expression during beige fat activation and facilitates the translocation of ACSL1 from the mitochondria to the endolysosomal pathway for degradation. Depletion of sortilin in adipocytes results in an increase of mitochondrial ACSL1 and the activation of AMPK/PGC1α signaling, thereby activating beige fat and preventing high-fat diet (HFD)-induced obesity and insulin resistance. Collectively, our findings indicate that sortilin controls adipose tissue fatty acid oxidation by substrate fuel selection during beige fat activation and provides a potential targeted approach for the treatment of metabolic diseases.

Enhanced diversity on connector hubs following sleep deprivation: Evidence from diffusion and functional magnetic resonance imaging.

Sleep deprivation has been demonstrated to exert widespread and intricate impacts on the brain network. The human brain network is a modular network composed of interconnected nodes. This network consists of provincial hubs and connector hubs, with provincial hubs having diverse connectivities within their own modules, while connector hubs distribute their connectivities across different modules. The latter is crucial for integrating information from various modules and ensuring the normal functioning of the modular brain. However, there has been a lack of systematic investigation into the impact of sleep deprivation on brain connector hubs. In this study, we utilized functional connectivity from resting-state functional magnetic resonance imaging, as well as structural connectivity from diffusion-weighted imaging, to systematically explore the variation of connector hub properties in the cerebral cortex after one night of sleep deprivation. The normalized participation coefficients (PCnorm) were utilized to identify connector hubs. In both the functional and structural networks, connector hubs exhibited a significant increase in average PCnorm, indicating the diversity enhancement of the connector hub following sleep deprivation. This enhancement is associated with increased network cost, reduced modularity, and decreased small-worldness, but enhanced global efficiency. This may potentially signify a compensatory mechanism within the brain following sleep deprivation. The significantly affected connector hubs were primarily observed in both the Control Network and Salience Network. We believe that the observed results reflect the increasing demand on the brain to invest more effort at preventing performance deterioration after sleep loss, in exchange for increased communication efficiency, especially involving systems responsible for neural resource allocation and cognitive control. These results have been replicated in an independent dataset. In conclusion, this study has enhanced our understanding of the compensatory mechanism in the brain response to sleep deprivation. This compensation is characterized by an enhancement in the connector hubs responsible for inter-modular communication, especially those related to neural resource and cognitive control. As a result, this compensation comes with a higher network cost but leads to an improvement in global communication efficiency, akin to a more random-like network manner.

Geniposide ameliorates bleomycin-induced pulmonary fibrosis in mice by inhibiting TGF-ß/Smad and p38MAPK signaling pathways.

Pulmonary fibrosis (PF) is an interstitial lung disease characterized by inflammation and fibrotic changes, with an unknown cause. In the early stages of PF, severe inflammation leads to the destruction of lung tissue, followed by upregulation of fibrotic factors like Transforming growth factor-ß (TGF-ß) and connective tissue growth factor (CTGF), which disrupt normal tissue repair. Geniposide, a natural iridoid glycoside primarily derived from the fruits of Gardenia jasminoides Ellis, possesses various pharmacological activities, including liver protection, choleretic effects, and anti-inflammatory properties. In this study, we investigated the effects of Geniposide on chronic inflammation and fibrosis induced by bleomycin (BLM) in mice with pulmonary fibrosis (PF). PF was induced by intratracheal instillation of bleomycin, and Geniposide(100/50/25mg•kg-1) was orally administered to the mice once a day until euthanasia(14 day/28 day). The Raw264.7 cell inflammation induced by LPS was used to evaluate the effect of Geniposide on the activation of macrophage. Our results demonstrated that Geniposide reduced lung coefficients, decreased the content of Hydroxyproline, and improved pathological changes in lung tissue. It also reduced the number of inflammatory cells and levels of pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF) of bleomycin-induced PF mice. At the molecular level, Geniposide significantly down-regulated the expression of TGF-ß1, Smad2/3, p38, and CTGF in lung tissues of PF mice induced by bleomycin. Molecular docking results revealed that Geniposide exhibited good binding activity with TGF-ß1, Smad2, Smad3, and p38. In vitro study showed Geniposide directly inhibited the activation of macrophage induced by LPS. In conclusion, our findings suggest that Geniposide can ameliorate bleomycin-induced pulmonary fibrosis in mice by inhibiting the TGF-ß/Smad and p38MAPK signaling pathways.

Toll-like Receptor 9 Inhibition Mitigates Fibroproliferative Responses in Translational Models of Pulmonary Fibrosis.

RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease for which current treatment options only slow clinical progression. Previously, we identified a subset of patients with IPF with an accelerated disease course associated with fibroblast expression of Toll-Like Receptor 9 (TLR9) mediated by interactions with its ligand mitochondrial DNA (mtDNA). OBJECTIVES: We aimed to show that TLR9 activation induces fibroproliferative responses that are abrogated by its antagonism by using two commercially-available indirect inhibitors and a proprietary, selective direct small molecule inhibitor. METHODS: We employed two independent cohorts of patients with IPF, multiple in vitro fibroblast cell culture platforms, an in vivo mouse model, and an ex vivo human precision cut lung slices system to investigate the clinical and biologic significance of TLR9 in this disease. MEASUREMENTS AND MAIN RESULTS: In two independent IPF cohorts, plasma mtDNA activates TLR9 in a manner associated with the expression of MCP-1, IL-6, TNFα, and IP-10 and worsened transplant-free survival. Our cell culture platform showed that TLR9 mediates fibroblast activation via TGFß1 and stiff substrates, and that its antagonism, particularly direct inhibition, ameliorates this process, including production of these TLR9 associated pharmacodynamic endpoints. We further demonstrated that direct TLR9 inhibition mitigates these fibroproliferative responses in our in vivo and ex vivo models of pulmonary fibrosis. CONCLUSIONS: In this novel study, we found that direct TLR9 inhibition mitigates fibroproliferative responses in preclinical models of pulmonary fibrosis. Our work demonstrates the therapeutic potential of direct TLR9 antagonism in IPF and related fibrotic lung diseases.

Design, synthesis and biological evaluation of N-salicyloyl tryptamine derivatives as multifunctional neuroprotectants for the treatment of ischemic stroke.

Ischemic stroke (IS) is a disease of high death and disability worldwide with few medications in clinical treatment. Neuroinflammation and oxidative stress are considered as crucial factors in the progression of IS. In our previous studies, N-salicyloyl tryptamine derivative (NST) L7 exhibited promising anti-inflammatory properties and is considered a potential clinical therapy for IS but had limited antioxidant capacity. Here, we have designed, synthesized, and biologically evaluated 30 novel NSTs for their neuroprotective effects against cerebral ischemia-reperfusion (CI/R) injury. To identify a multifunctional neuroprotectant with enhanced antioxidant and anti-inflammatory capacity, as well as an effective therapeutic agent for CI/R damage. Among them, M11 exhibited synergistic highly anti-oxidant, anti-inflammatory, anti-ferroptosis, and anti-apoptosis effects and surpassed the parent compound L7. Further studies demonstrated that the synergistic and efficient neuroprotective role of M11 was mainly achieved by activating Nrf2 and stimulating its downstream target HO-1/GCLC/NQO1/GPX4. In addition, M11 possessed good blood-brain barrier permeability. Moreover, M11 effectively reduced cerebral infarct volume and improved neurological deficits in MCAO/R mice. Its hydrochloride form, M11·HCl, exhibited better pharmacokinetic properties, high safety, and a significant reduction in infarct volume, which is comparable to Edaravone. In conclusion, our findings suggested that M11 capable of activating Nrf2, could represent a promising candidate agent for IS.

Entrepreneur's social identity, decision logic, and resource bootstrapping behaviors: An empirical study of the fsQCA method.

While resource bootstrapping is widely employed by novice entrepreneurs,and social identities and decision logic are studied as important antecedents of entrepreneurs' adoption of resource bootstrapping behaviors, both scholars and practitioners have but a hazy understanding on the configuration effect of entrepreneur's social identities and decision logic on resource bootstrapping behaviors. In this paper, we combined the necessary condition analysis (NCA) and fuzzy set qualitative comparative analysis (fsQCA) to explore the configuration effects of entrepreneur's social identity and decision logic on resource bootstrapping behaviors. Analysis of 411 questionnaire date acquired from novice entrepreneurs, we found that none of single antecedent condition of both the entrepreneur's social identity and decision logic constitute the necessary condition of novice entrepreneurs' high resource bootstrapping behaviors. We also found a substitutive relationship between Darwinian social identity and communitary social identity that will lead the novice entrepreneurs with high dual effectual-causal decision logic to choose high joint utilization bootstrapping, and a complementary relationship between the three social identities of novice entrepreneurs such that those with high dual effectual-causal decision logic prefer different resource bootstrapping behaviors because of different social identities.Furthermore, we found that the core and edge conditions in the decision logic play different roles in the resource bootstrapping behaviors of novice entrepreneurs, with the core decision logic conditions having a greater impact on the resource bootstrapping behaviors. These findings deepen our understanding of the causal complexity among entrepreneur's social identity, decision logic and resource bootstrapping behaviors. It also provides theoretical guidance for effective resource integration for novice entrepreneurs facing resource constraints.

Fenamates: Forgotten treasure for cancer treatment and prevention: Mechanisms of action, structural modification, and bright future.

Fenamates as classical nonsteroidal anti-inflammatory agents are widely used for relieving pain. Preclinical studies and epidemiological data highlight their chemo-preventive and chemotherapeutic potential for cancer. However, comprehensive reviews of fenamates in cancer are limited. To accelerate the repurposing of fenamates, this review summarizes the results of fenamates alone or in combination with existing chemotherapeutic agents. This paper also explores targets of fenamates in cancer therapy, including COX, AKR family, AR, gap junction, FTO, TEAD, DHODH, TAS2R14, ion channels, and DNA. Besides, this paper discusses other mechanisms, such as regulating Wnt/ß-catenin, TGF-ß, p38 MAPK, and NF-κB pathway, and the regulation of the expressions of Sp, EGR-1, NAG-1, ATF-3, ErbB2, AR, as well as the modulation of the tumor immune microenvironment. Furthermore, this paper outlined the structural modifications of fenamates, highlighting their potential as promising leads for anticancer drugs.

Reference guides for the safe use of drugs during pregnancy: a systematic review and comparative analysis.

PURPOSE: To comprehensively evaluate and compare all the available reference guides for the safe use of drugs during pregnancy, with the goal of determining the scientificity and reliability of these reference guides. METHODS: We searched PubMed, EMbase, CNKI, Wanfang Database, and VIP database to comprehensively identify the available reference guides. Moreover, we selected 103 drugs based on relevant literatures, and compared the recommendations of each drug from different reference guides. RESULTS: A total of 14 available reference guides were identified. However, none of these reference guides assessed the risk of bias of original studies or the quality of current evidence. Seven reference guides adopted expert consensus method to formulate pregnancy recommendations, while the rest reference guides did not report the formation method. Moreover, 77.7% of the selected drugs had inconsistent recommendations among different reference guides. In addition, the referenced human and animal studies for the same drug differed among different reference guides. CONCLUSION: Our results indicate that current reference guides for the safe use of drugs during pregnancy are less scientific and reliable, and there are considerable discrepancies in recommendations from different reference guides concerning drug use during pregnancy. The reasons for the discrepancies in recommendations include ① the literature search in most reference guides was not comprehensive, ② none of the available reference guides assessed the risk of bias of original studies or the quality of current evidence, and ③ the method adopted by current reference guides to formulate recommendations had obvious subjectivity and lacked of scientificity.

cGAS Expression is Enhanced in Systemic Sclerosis Associated Interstitial Lung Disease and Stimulates Inflammatory Myofibroblast Activation.

Objective: The lungs of patients with Systemic Sclerosis Associated Interstitial Lung Disease (SSc-ILD) contain inflammatory myofibroblasts arising in association with fibrotic stimuli and perturbed innate immunity. The innate immune DNA binding receptor Cyclic GMP-AMP synthase (cGAS) is implicated in inflammation and fibrosis, but its involvement in SSc-ILD remains unknown. We examined cGAS expression, activity, and therapeutic potential in SSc-ILD using cultured fibroblasts, precision cut lung slices (PCLS), and a well-accepted animal model. Methods: Expression and localization of cGAS, cytokines, and type 1 interferons were evaluated in SSc-ILD lung tissues, bronchoalveolar lavage (BAL), and isolated lung fibroblasts. CGAS activation was assessed in a publicly available SSc-ILD single cell RNA sequencing dataset. Production of cytokines, type 1 interferons, and αSMA elicited by TGFß1 or local substrate stiffness were measured in normal human lung fibroblasts (NHLFs) via qRT-PCR, ELISA, and immunofluorescence. Small molecule cGAS inhibition was tested in cultured fibroblasts, human PCLS, and the bleomycin pulmonary fibrosis model. Results: SSc-ILD lung tissue and BAL are enriched for cGAS, cytokines, and type 1 interferons. The cGAS pathway shows constitutive activation in SSc-ILD fibroblasts and is inducible in NHLFs by TGFß1 or mechanical stimuli. In these settings, and in human PCLS, cGAS expression is paralleled by the production of cytokines, type 1 interferons, and αSMA that are mitigated by a small molecule cGAS inhibitor. These findings are recapitulated in the bleomycin mouse model. Conclusion: cGAS signaling contributes to pathogenic inflammatory myofibroblast phenotypes in SSc-ILD. Inhibiting cGAS or its downstream effectors represents a novel therapeutic approach.

Distinct prophage gene profiles of Staphylococcus aureus strains from atopic dermatitis patients and healthy individuals.

Staphylococcus aureus strains exhibit varying associations with atopic dermatitis (AD), but the genetic determinants underpinning the pathogenicity are yet to be fully characterized. To reveal the genetic differences between S. aureus strains from AD patients and healthy individuals (HE), we developed and employed a random forest classifier to identify potential marker genes responsible for their phenotypic variations. The classifier was able to effectively distinguish strains from AD and HE. We also uncovered strong links between certain marker genes and phage functionalities, with phage holin emerging as the most pivotal differentiating factor. Further examination of S. aureus gene content highlighted the genetic diversity and functional implications of prophages in driving differentiation between strains from AD and HE. The HE group exhibited greater gene content diversity, largely influenced by their prophages. While strains from both AD and HE universally housed prophages, those in the HE group were distinctively higher at the strain level. Moreover, although prophages in the HE group exhibited variously higher enrichment of differential functions, the AD group displayed a notable enrichment of virulence factors within their prophages, underscoring the important contribution of prophages to the pathogenesis of AD-associated strains. Overall, prophages significantly shape the genetic and functional profiles of S. aureus strains, shedding light on their pathogenic potential and elucidating the mechanisms behind the phenotypic variations in AD and HE environments. IMPORTANCE: Through a nuanced exploration of Staphylococcus aureus strains obtained from atopic dermatitis (AD) patients and healthy controls (HE), our research unveils pivotal genetic determinants influencing their pathogenic associations. Utilizing a random forest classifier, we illuminate distinct marker genes, with phage holin emerging as a critical differential factor, revealing the profound impact of prophages on genetic and pathogenic profiles. HE strains exhibited a diverse gene content, notably shaped by unique, heightened prophages. Conversely, AD strains emphasized a pronounced enrichment of virulence factors within prophages, signifying their key role in AD pathogenesis. This work crucially highlights prophages as central architects of the genetic and functional attributes of S. aureus strains, providing vital insights into pathogenic mechanisms and phenotypic variations, thereby paving the way for targeted AD therapeutic approaches and management strategies by demystifying specific genetic and pathogenic mechanisms.

Inhibition of FBP1 expression by KMT5A through TWIST1 methylation is one of the mechanisms leading to chemoresistance in breast cancer.

Lysine methyltransferase 5A (KMT5A) is the sole mammalian enzyme known to catalyse the mono­methylation of histone H4 lysine 20 and non­histone proteins such as p53, which are involved in the occurrence and progression of numerous cancers. The present study aimed to determine the function of KMT5A in inducing docetaxel (DTX) resistance in patients with breast carcinoma by evaluating glucose metabolism and the underlying mechanism involved. The upregulation or downregulation of KMT5A­related proteins was examined after KMT5A knockdown in breast cancer (BRCA) cells by Tandem Mass Tag proteomics. Through differential protein expression and pathway enrichment analysis, the upregulated key gluconeogenic enzyme fructose­1,6­bisphosphatase 1 (FBP1) was discovered. Loss of FBP1 expression is closely related to the development and prognosis of cancers. A dual­luciferase reporter gene assay confirmed that KMT5A inhibited the expression of FBP1 and that overexpression of FBP1 could enhance the chemotherapeutic sensitivity to DTX through the suppression of KMT5A expression. The KMT5A inhibitor UNC0379 was used to verify that DTX resistance induced by KMT5A through the inhibition of FBP1 depended on the methylase activity of KMT5A. According to previous literature and interaction network structure, it was revealed that KMT5A acts on the transcription factor twist family BHLH transcription factor 1 (TWIST1). Then, it was verified that TWSIT1 promoted the expression of FBP1 by using a dual­luciferase reporter gene experiment. KMT5A induces chemotherapy resistance in BRCA cells by promoting cell proliferation and glycolysis. After the knockdown of the KMT5A gene, the FBP1 related to glucose metabolism in BRCA was upregulated. KMT5A knockdown expression and FBP1 overexpression synergistically inhibit cell proliferation and block cells in the G2/M phase. KMT5A inhibits the expression of FBP1 by methylating TWIST1 and weakening its promotion of FBP1 transcription. In conclusion, KMT5A was shown to affect chemotherapy resistance by regulating the cell cycle and positively regulate glycolysis­mediated chemotherapy resistance by inhibiting the transcription of FBP1 in collaboration with TWIST1. KMT5A may be a potential therapeutic target for chemotherapy resistance in BRCA.

Artificial intelligence in dentistry: A bibliometric analysis from 2000 to 2023.

Background/purpose: Artificial intelligence (AI) is reshaping clinical practice in dentistry. This study aims to provide a comprehensive overview of global trends and research hotspots on the application of AI to dentistry. Materials and methods: Studies on AI in dentistry published between 2000 and 2023 were retrieved from the Web of Science Core Collection. Bibliometric parameters were extracted and bibliometric analysis was conducted using VOSviewer, Pajek, and CiteSpace software. Results: A total of 651 publications were identified, 88.7 % of which were published after 2019. Publications originating from the United States and China accounted for 34.5 % of the total. The Charité Medical University of Berlin was the institution with the highest number of publications, and Schwendicke and Krois were the most active authors in the field. The Journal of Dentistry had the highest citation count. The focus of AI in dentistry primarily centered on the analysis of imaging data and the dental diseases most frequently associated with AI were periodontitis, bone fractures, and dental caries. The dental AI applications most frequently discussed since 2019 included neural networks, medical devices, clinical decision support systems, head and neck cancer, support vector machine, geometric deep learning, and precision medicine. Conclusion: Research on AI in dentistry is experiencing explosive growth. The prevailing research emphasis and anticipated future development involve the establishment of medical devices and clinical decision support systems based on innovative AI algorithms to advance precision dentistry. This study provides dentists with valuable insights into this field.

Blue Laser Triggered Hemostatic Peptide Hydrogel for Gastrointestinal Bleeding Treatment.

In an emergency, nonvariceal upper gastrointestinal bleeding (NVUGIB), endoscopic hemostasis is considered the gold standard intervention. However, current endoscopic hemostasis is very challenging to manage bleeding in large-diameter or deep lesions highly prone to rebleeding risk. Herein, a novel hemostatic peptide hydrogel (HPH) is reported, consisting of a self-assembly peptide sequence CFLIVIGSIIVPGDGVPGDG (PFV) and gelatin methacryloyl (GelMA), which can be triggered by blue laser endoscopy (BLE) for nonvariceal upper gastrointestinal bleeding treatment without recurring bleeding concerns. Upon contact with GelMA solution, PFV immediately fibrillates into ß-sheet nanofiber and solvent-induced self-assembly to form HPH gel. HPH nanofiber networks induced ultrafast coagulation by enveloping blood cells and activating platelets and coagulation factors even to the blood with coagulopathy. Besides its remarkable hemostatic performance in artery and liver injury models, HPH achieves instant bleeding management in porcine NVUGIB models within 60 s by preventing the rebleeding risk. This work demonstrates an extraordinary hemostatic agent for NVUGIB intervention by BLE for the first time, broadening potential application scenarios, including patients with coagulopathy and promising clinical prospects.

Are older adults less generous? Age differences in emotion-related social decision making.

In social interaction, age-related differences in emotional processing may lead to varied social decision making between young and older adults. However, previous studies of social decision making have paid less attention to the interactants' emotions, leaving age differences and underlying neural mechanisms unexplored. To address this gap, the present study combined functional and structural magnetic resonance imaging, employing a modified dictator game task with recipients displaying either neutral or sad facial expressions. Behavioral results indicated that although older adults' overall allocations did not differ significantly from those of young adults, older adults' allocations showing a decrease in emotion-related generosity compared to young adults. Using representational similarity analysis, we found that older adults showed reduced neural representations of recipients' emotions and gray matter volume in the right anterior cingulate gyrus (ACC), right insula, and left dorsomedial prefrontal cortex (DMPFC) compared to young adults. More importantly, mediation analyses indicated that age influenced allocations not only through serial mediation of neural representations of the right insula and left DMPFC, but also through serial mediation of the mean gray matter volume of the right ACC and left DMPFC. This study identifies the potential neural pathways through which age affects emotion-related social decision making, advancing our understanding of older adults' social interaction behavior that they may not be less generous unless confronted with individuals with specific emotions.

Robust Transient Semi-Glue Tape: Ultrastrong Adhesion Empowered by Water Activation and Self-Locking.

In adhesive industry, tapes are renowned for their superior flexibility, repeatability, and ease of storage compared to glues. However, conventional adhesive tapes often suffer from low adhesion strength (<500 kPa). This work introduces an innovative adhesive tape composed of an amphiphilic copolymer and a hydrophobic ionic liquid, achieving an ultrahigh adhesion strength of up to 3.1 MPa on various substrates, making a record-high strength to date for tape-type adhesives. This exceptional adhesion performance is facilitated by water droplets applied at the bonding interface, transforming the adhesive surface into a glue-like property without the need for curing treatments or additional auxiliary equipment. By combining the advantageous features of both glues and tapes, these adhesives are termed as transient semi-glue tapes (TSGT). The mechanism behind such water activation and self-locking process is elucidated, and a general preparation approach is developed. Furthermore, the repeatability and recyclability of TSGT are demonstrated, offering an ingenious solution to this long-standing engineering challenge.

Intergenerational or intragenerational learning? The relationship between interpersonal neural synchrony and older adult's learning acquisition.

OBJECTIVES: Lifelong learning facilitates active ageing, and intragenerational learning-the process by which older adults learn from their peers-is an effective means of achieving this goal. The present research aims to elucidate the mechanisms and differences between intergenerational and intragenerational learning models for older adults as evidenced by brain-to-brain synchrony. METHODS: Fifty-six instructor-learner dyads completed a study comparing intergenerational and intragenerational learning models, as well as task difficulty. The study utilized a block puzzle task and functional near-infrared spectroscopy (fNIRS) for hyperscanning. RESULTS: The instructor-learner dyads showed greater interpersonal neural synchrony (INS) and learning acquisition in the intragenerational learning model in the difficult task condition (t (54) = 3.49, p < 0.01), whereas the two learning models yielded similar results in the easy condition (t (54) = 1.96, p = 0.06). In addition, INS and self-efficacy mediated the association between learning models and learning acquisition in older adults (b = 0.14, SEM = 0.04, 95 % CI [0.01 0.16]). DISCUSSION: This study is the first to provide evidence of interbrain synchrony in an investigation of the intragenerational learning model in older adults. Our findings suggest that intra-learning is as effective as traditional inter-learning and may be more effective in certain contexts, such as difficult tasks. Encouraging intra-learning in community service or educational activities can effectively mitigate the challenge of limited volunteers and enhance learning acquisition among older adults.

A new artificial intelligence system for both stomach and small-bowel capsule endoscopy.

BACKGROUND AND AIMS: Despite the benefits of artificial intelligence in small-bowel (SB) capsule endoscopy (CE) image reading, information on its application in the stomach and SB CE is lacking. METHODS: In this multicenter, retrospective diagnostic study, gastric imaging data were added to the deep learning-based SmartScan (SS), which has been described previously. A total of 1069 magnetically controlled GI CE examinations (comprising 2,672,542 gastric images) were used in the training phase for recognizing gastric pathologies, producing a new artificial intelligence algorithm named SS Plus. A total of 342 fully automated, magnetically controlled CE examinations were included in the validation phase. The performance of both senior and junior endoscopists with both the SS Plus-assisted reading (SSP-AR) and conventional reading (CR) modes was assessed. RESULTS: SS Plus was designed to recognize 5 types of gastric lesions and 17 types of SB lesions. SS Plus reduced the number of CE images required for review to 873.90 (median, 1000; interquartile range [IQR], 814.50-1000) versus 44,322.73 (median, 42,393; IQR, 31,722.75-54,971.25) for CR. Furthermore, with SSP-AR, endoscopists took 9.54 minutes (median, 8.51; IQR, 6.05-13.13) to complete the CE video reading. In the 342 CE videos, SS Plus identified 411 gastric and 422 SB lesions, whereas 400 gastric and 368 intestinal lesions were detected with CR. Moreover, junior endoscopists remarkably improved their CE image reading ability with SSP-AR. CONCLUSIONS: Our study shows that the newly upgraded deep learning-based algorithm SS Plus can detect GI lesions and help improve the diagnostic performance of junior endoscopists in interpreting CE videos.

N-Salicyloyl Tryptamine Derivatives as Potent Neuroinflammation Inhibitors by Constraining Microglia Activation via a STAT3 Pathway.

Neuroinflammation is an important factor that exacerbates neuronal death and abnormal synaptic function in neurodegenerative diseases (NDDs). Due to the complex pathogenesis and the presence of blood-brain barrier (BBB), no effective clinical drugs are currently available. Previous results showed that N-salicyloyl tryptamine derivatives had the potential to constrain the neuroinflammatory process. In this study, 30 new N-salicyloyl tryptamine derivatives were designed and synthesized to investigate a structure-activity relationship (SAR) for the indole ring of tryptamine in order to enhance their antineuroinflammatory effects. Among them, both in vitro and in vivo compound 18 exerted the best antineuroinflammatory effects by suppressing the activation of microglia, which is the culprit of neuroinflammation. The underlying mechanism of its antineuroinflammatory effect may be related to the inhibition of transcription, expression and phosphorylation of signal transducer and activator of transcription 3 (STAT3) that subsequently regulated downstream cyclooxygenase-2 (COX-2) expression and activity. With its excellent BBB permeability and pharmacokinetic properties, compound 18 exhibited significant neuroprotective effects in the hippocampal region of lipopolysaccharides (LPS)-induced mice than former N-salicyloyl tryptamine derivative L7. In conclusion, compound 18 has provided a new approach for the development of highly effective antineuroinflammatory therapeutic drugs targeting microglia activation.

SIRT6 positively regulates antiviral response in a bony fish, the Chinese perch Siniperca chuatsi.

SIRT6, a key member of the sirtuin family, plays a pivotal role in regulating a number of vital biological processes, including energy metabolism, oxidative stress, and immune system modulation. Nevertheless, the function of SIRT6 in bony fish, particularly in the context of antiviral immune response, remains largely unexplored. In this study, a sirt6 was cloned and characterized in a commercial fish, the Chinese perch (Siniperca chuatsi). The SIRT6 possesses conserved SIR2 domain with catalytic core region when compared with other vertebrates. Tissue distribution analysis indicated that sirt6 was expressed in all detected tissues, and the sirt6 was significantly induced following infection of infectious haemorrhagic syndrome virus (IHSV). The overexpression of SIRT6 resulted in significant upregulation of interferon-stimulated genes (ISGs), such as viperin, mx, isg15, irf3 and ifp35, and inhibited viral replication. It was further found that SIRT6 was located in nucleus and could enhance the expression of ISGs induced by type I and II IFNs. These findings may provide new information in relation with the function of SIRT6 in vertebrates, and with viral prevention strategy development in aquaculture.