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Abstract Recently, the widespread adoption of artificial intelligence (AI) has given rise to a significant trust crisis, stemming from the persistent emergence of issues in practical applications. As a crucial component of AI, data has a profound impact on the trustworthiness of AI. Nevertheless, researchers have struggled with the challenge of rationally assessing data quality, primarily due to the scarcity of versatile and effective evaluation methods. To address this trouble, a multi-dimensional hierarchical evaluation system (MDHES) is proposed to estimate the data quality. Initially, multiple key dimensions are devised to evaluate specific data conditions separately by the calculation of individual scores. Then, the strengths and weaknesses among various dimensions can be provided a clearer understanding. Furthermore, a comprehensive evaluation method, incorporating a fuzzy evaluation model, is developed to synthetically evaluate the data quality. Then, this evaluation method can achieve a dynamic balance, and meanwhile achieve a harmonious integration of subjectivity and objectivity criteria to ensure a more precise assessment result. Finally, rigorous experiment verification and comparison in both benchmark problems and real-world applications demonstrate the effectiveness of the proposed MDHES, which can accurately assess data quality to provide a strong data support for the development of trustworthy AI.

Abstract The resource-assisted processing operation involves the coupling of multi-dimensional sub-problem, which poses a challenge in scheduling system. In this study, a dimension-aware gain-sharing knowledge algorithm (DGSK) is presented to address the distributed hybrid flowshop scheduling problem with resource-dependent processing times (DHFSP-RDPT), where the makespan is to be minimized. Firstly, by analyzing the mathematical model of the DHFSP-RDPT, four problem-specific lemmas and two novel resource reallocation rules are proposed. The DGSK begin with a high-performance initial population, which is generated by three knowledge-driven heuristics in hybrid way. Next, a discrete evolution-based search mechanism assists the DGSK to extend the search in solution space. Furthermore, a dimension-aware two-stage local search combined with meta-Lamarckian learning method is embedded to enhance the local search ability for the multidimensional problems. Finally, the proposed algorithm is measured on a series of instances based on real production data. The results demonstrate that the DGSK improves the performance by in solving DHFSP-RDPT compared to the state-of-the-art methods.

Acute lung injury (ALI) has multiple causes and can easily progress to acute respiratory distress syndrome (ARDS) if not properly treated. Nuclear factor κB (NF-κB) is a key pathway in the treatment of ALI/ARDS. By exploring the relevance of NF-κB and the pathogenesis of this disease, it was found that this disease was mainly associated with inflammation, dysfunction of the endothelial barrier, oxidative stress, impaired clearance of alveolar fluid, and coagulation disorders. Traditional Chinese medicine (TCM) has the characteristics of multitargeting, multipathway effects, and high safety, which can directly or indirectly affect the treatment of ALI/ARDS. This article summarizes the mechanism and treatment strategies of TCM in recent years through intervention in the NF-κB-related signaling pathways for treating ALI/ARDS. It provides an overview from the perspectives of Chinese herbal monomers, TCM couplet medicines, TCM injections, Chinese herbal compounds, and Chinese herbal preparations, offering insights into the prevention and treatment of ALI/ARDS with TCM.

Background: The extensive community of gut microbiota significantly influences various biological functions throughout the body, making its characterization a focal point in biomedicine research. Over the past few decades, studies have revealed a potential link between specific gut bacteria, their associated metabolic pathways, and influenza. Bacterial metabolites can communicate directly or indirectly with organs beyond the gut via the intestinal barrier, thereby impacting the physiological functions of the host. As the microbiota increasingly emerges as a ‘gut signature’ in influenza, gaining a deeper understanding of its role may offer new insights into its pathophysiological relevance and open avenues for novel therapeutic targets. In this Review, we explore the differences in gut microbiota between healthy individuals and those with influenza, the relationship between gut microbiota metabolites and influenza, and potential strategies for preventing and treating influenza through the regulation of gut microbiota and its metabolites, including fecal microbiota transplantation and microecological preparations. Methods: We utilized PubMed and Web of Science as our search databases, employing keywords such as “influenza,” “gut microbiota,” “traditional Chinese medicine,” “metabolites,” “prebiotics,” “probiotics,” and “machine learning” to retrieve studies examining the potential therapeutic connections between the modulation of gut microbiota and its metabolites in the treatment of influenza. The search encompassed literature from the inception of the databases up to December 2023. Results: Fecal microbiota transplantation (FMT), microbial preparations (probiotics and prebiotics), and traditional Chinese medicine have unique advantages in regulating intestinal microbiota and its metabolites to improve influenza outcomes. The primary mechanism involves increasing beneficial intestinal bacteria such as Bacteroidetes and Bifidobacterium while reducing harmful bacteria such as Proteobacteria. These interventions act directly or indirectly on metabolites such as short-chain fatty acids (SCFAs), amino acids (AAs), bile acids, and monoamines to alleviate lung inflammation, reduce viral load, and exert anti-influenza virus effects. Conclusion: The gut microbiota and its metabolites have direct or indirect therapeutic effects on influenza, presenting broad research potential for providing new directions in influenza research and offering references for clinical prevention and treatment. Future research should focus on identifying key strains, specific metabolites, and immune regulation mechanisms within the gut microbiota to accurately target microbiota interventions and prevent respiratory viral infections such as influenza.

Summary: Background: Mesenteric adipose tissue (mAT) hyperplasia, known as creeping fat, is a pathologic characteristic of Crohn’s disease (CD). In our previously reported cohort, we observed that Achromobacter pulmonis was the most abundant and prevalent bacteria cultivated from creeping fat. Methods: A whole genomic sequencing and identification of T3SS orthologs of mAT-derived A. pulmonis were used. A functional type III secretion system (T3SS) mediated the pathogenic potential of A. pulmonis in vitro and in mouse colitis model. Furthermore, a T3SS Finder pipeline was introduced to evaluate gut bacterial T3SS orthologs in the feces of CD patients, ulcerative colitis and colorectal cancer patients. Findings: Here, we reveal that mAT-derived A. pulmonis possesses a functional T3SS, aggravates colitis in mice via T3SS, and exhibits T3SS-dependent cytotoxicity via a caspase-independent mechanism in macrophages and epithelial cells, which demonstrated the pathogenic potential of the T3SS-harboring A. pulmonis. Metagenomic analyses demonstrate an increased abundance of Achromobacter in the fecal of Crohn's disease patients compared to healthy controls. A comprehensive comparison of total microbial vT3SS abundance in various intestine diseases demonstrated that the specific enrichment of vT3SS genes was shown in fecal samples of CD, neither ulcerative colitis nor colorectal cancer patients, and ten T3SS gene-based biomarkers for CD were discovered and validated in a newly recruited CD cohort. Furthermore, treatment with exclusive enteral nutrition (EEN), an intervention that improves CD patient symptomatology, was found associated with a significant reduction in the prevalence of T3SS genes in fecal samples. Interpretation: These findings highlight the pathogenic significance of T3SSs in the context of CD and identify specific T3SS genes that could potentially function as biomarkers for diagnosing and monitoring the clinical status of CD patients. Funding: This work is supported by the National Key Research and Development Program of China (2020YFA0907800), the China Postdoctoral Science Foundation (2023M744089), the National Natural Science Foundation of China (32000096), the Shenzhen Science and Technology Programs (KQTD20200820145822023, RCIC20231211085944057, and ZDSYS20220606100803007), National Key Clinical Discipline, Guangdong Provincial Clinical Research Center for Digestive Diseases (2020B1111170004), Qingfeng Scientific Research Fund of the China Crohn’s & Colitis Foundation (CCCF) (CCCF-QF-2022B71-1), and the Sixth Affiliated Hospital, Sun Yat-sen University Clinical Research 1010 Program 1010CG(2023)-08. These funding provided well support for this research work, which involved data collection, analysis, interpretation, patient recruitment and so on.

Background: Left ventricular thrombus (LVT) is a significant complication in STEMI. Previous studies were conducted prior to modern timely percutaneous reperfusion networks. Current expert opinion suggests incidence in the current era has decreased. We conducted a systematic review and meta-analysis to better understand the incidence and diagnosis of LVT in patients with STEMI treated with timely percutaneous techniques as assessed by multimodality imaging. Methods: Cochrane, EMBASE, LILACS, and MEDLINE were searched over the last 10 years only including studies using contemporary techniques. The primary outcome was detection of LVT in patients via echocardiogram with or without contrast or Cardiac MRI (cMRI) following STEMI (both anterior and any territory) treated with PCI. Data was pooled across studies and statistical analysis was conducted via random effects model. Results: 31 studies were included. 18 studies included data on any territory STEMI, totaling 14,172 patients, and an incidence of 5.6% [95% CI 4.3–7.0]. 18 studies were included in analysis for anterior STEMI, totaling 7382 patients and incidence of 12.7% [95% CI 9.8–15.6]. Relative to cMRI as a gold standard, the sensitivity of non-contrast echocardiography to detect LVT was 58.2% [95% CI 46.6–69.2] with a specificity of 97.8% [95% CI 96.3–98.8]. Conclusions: Incidence of LVT in STEMI patients treated with contemporary timely percutaneous revascularization is in keeping with historical data and remains significant, suggesting this remains an ongoing issue for further investigation. Numerically, both cMRI and contrast echo detected more LVT compared to non-contrast echo in any-territory STEMI patients.

Background & Aims: As the most abundant memory T cells and major source of tumor necrosis factor α in the intestinal mucosa of Crohn’s disease (CD) patients, CD4+ tissue-resident memory T (TRM) cells play a critical role in CD pathogenesis. We investigated the role of metabolic reprogramming in the regulation of proinflammatory and apoptosis-resistant phenotype for CD4+ TRM cells. Methods: CD4+ TRM cells were collected from intestinal resection tissues from control and CD patients. Transcriptomic and metabolomic analysis were performed to identify metabolic characteristics of CD4+ TRM cells. Enzyme-linked immunosorbent assay and quantitative polymerase chain reaction experiments were used to assess cytokines level in CD4+ TRM cells; activation-induced cell apoptosis rate was evaluated by flow cytometry. Transwell assay and wound healing assay were performed to detect the effect of CD4+ TRM cells on the migration of normal intestinal epithelial cells. Results: Transcriptomic data combined with unbiased metabolomic analysis revealed an increased fatty acid oxidation (FAO) phenotype existed in CD4+ TRM cells from CD patients. The lipidomic data and stable isotope tracer experiments demonstrated that CD4+ TRM cells up-regulated their lipid lipolysis and fatty acid uptake to fuel FAO in CD patients. Mechanistically, the activated nuclear factor kappa B signaling increased transcription of genes involved in lipid lipolysis, fatty acid uptake, and oxidation in CD4+ TRM cells from CD patients. Targeting FAO of CD4+ TRM cells reversed their apoptosis-resistant and proinflammatory phenotype in CD patients. Conclusions: CD4+ TRM cells process an accelerated FAO mediated by activated nuclear factor kappa B signaling in CD patients; targeting FAO could reverse their apoptosis-resistant and proinflammatory phenotype. These findings shed a new light on the pathogenic mechanism investigation and novel therapy development in CD patients.

AbstractContext Polygonum cuspidatum Sieb. et Zucc (Polygonaceae), the root of which is included in the Chinese Pharmcopoeia under the name ‘Huzhang', has a long history as a medicinal plant and vegetable. Polygonum cuspidatum has been used in traditional Chinese medicine for the treatment of inflammation, hyperlipemia, etc.Objective This article reviews the pharmacological action and the clinical applications of Polygonum cuspidatum and its extracts, whether in vivo or in vitro. We also summarized the main phytochemical constituents and pharmacokinetics of Polygonum cuspidatum and its extracts.Methods The data were retrieved from major medical databases, such as CNKI, PubMed, and SinoMed, from 2014 to 2022. Polygonum cuspidatum, pharmacology, toxicity, clinical application, and pharmacokinetics were used as keywords.Results The rhizomes, leaves, and flowers of Polygonum cuspidatum have different phytochemical constituents. The plant contains flavonoids, anthraquinones, and stilbenes. Polygonum cuspidatum and the extracts have anti-inflammatory, antioxidation, anticancer, heart protection, and other pharmacological effects. It is used in the clinics to treat dizziness, headaches, traumatic injuries, and water and fire burns.Conclusions Polygonum cuspidatum has the potential to treat many diseases, such as arthritis, ulcerative colitis, asthma, and cardiac hypertrophy. It has a broad range of medicinal applications, but mainly focused on root medication; its aerial parts should receive more attention. Pharmacokinetics also need to be further investigated.

Background: Pulmonary Hypertension (PH) is a condition with several cardiopulmonary etiologies that has the potential of progressing to right heart failure without proper intervention. After a history, physical exam, and investigations, cases of suspected PH typically undergo imaging via a (TTE). This is a resource-intensive procedure that is less accessible in remote communities. However, point of care ultrasound (POCUS), a portable ultrasound administered at the bedside, has potential to aid in the diagnostic process of PH. Methods: The MEDLINE, , and CENTRAL databases were searched to screen the intersection of POCUS and PH. Studies involved adult patients, and only English articles were accepted. Reviews, case reports, unfinished research, and conference abstracts were excluded. Our aim was to identify primary studies that correlated POCUS scan results and additional clinical findings related to PH. Results: Nine studies were included after our search. In these studies, POCUS was effective in identifying dilatation of inferior (IVC); internal jugular vein (IJV); and hepatic, portal, and veins in patients with PH. The presence of pericardial effusion, effusion, or b-lines on POCUS are also associated with PH. Conclusions: This review suggests important potential for the use of POCUS in the initial screening of PH. IVC and basic cardiopulmonary POCUS exams are key for PH screening in patients with . Right-heart dilatation can be visualized, and peripheral veins may be scanned based on clinical suspicion. POCUS offers screening as an extension of a physical exam, with direct visualization of cardiac morphology. However, more studies are required to develop a statistically validated POCUS exam for PH diagnosis. More studies should also be conducted at the primary-care level to evaluate the value of screening using POCUS for PH in less-differentiated patients.

Abstract Objective To explore the impact of inflammatory factors on the incidence of cerebral small vessel disease (CSVD), we performed a mendelian randomization (MR) study to analyze the causal relationship between multiple inflammatory factors and CSVD imaging markers and utilized summary‐data‐based mendelian randomization (SMR) analysis to infer whether the impact of instrumental variables (IVs) on disease is mediated by gene expression or DNA methylation. Methods Using public databases such as UKB and IEU, and original genome‐wide association studies, we obtained IVs related to exposure (inflammatory factors) and outcome (CSVD imaging markers). We performed the inverse variance weighted, weighted median, and MR‐Egger methods to assess causal effects between exposure and outcome in univariate MR analysis. To evaluate their heterogeneity, a series of sensitivity analyses were conducted, including the Cochrane Q test, MR‐Egger intercept test, MR‐Presso, and leave‐one‐out analysis. We also applied mediation and multivariate MR analysis to explore the interactions between positive exposures on the same outcome. Additionally, we conducted the SMR, which utilizes instruments within or near relevant genes in blood or brain tissues, to elucidate the causal associations with CSVD markers. Results ABO Univariate MR of multiple cohorts revealed that the risk of small vessel stroke (SVS) increases with elevated levels of TNF‐related apoptosis‐inducing ligand (TRAIL, OR, 1.23, 95% CI, 1.08–1.39) and interleukin‐1 receptor‐like 2, (IL‐1RL2, OR, 1.29, 95% CI, 1.04–1.61). IL‐18 was a potential risk factor for extensive basal ganglia perivascular space burden (BGPVS, OR, 1.02, 95% CI, 1.00–1.05). Moreover, the risk of extensive white matter perivascular space burden (WMPVS) decreased with rising levels of E‐selectin (OR, .98, 95% CI, .97–1.00), IL‐1RL2 (OR, .97, 95% CI, .95–1.00), IL‐3 receptor subunit alpha (IL‐3Ra, OR, .98, 95% CI, .97–1.00), and IL‐5 receptor subunit alpha (IL‐5Ra, OR, .98, 95% CI, .97–1.00). Mediation and multivariate MR analysis indicated that E‐selectin and IL‐3Ra might interact during the pathogenesis of WMPVS. SMR estimates showed that TRAIL‐related IVs rs5030044 and rs2304456 increased the risk of SVS by increasing the expression of gene Kininogen‐1 (KNG1) in the cerebral cortex, particularly in the frontal cortex (βsmr = .10, Psmr = .003, FDR = .04). Instruments (rs507666 and rs2519093) related to E‐selectin and IL‐3Ra could increase the risk of WMPVS by enhancing DNA methylation of the gene ABO in blood tissue (βsmr = .01–.02, Psmr = .001, FDR = .01–.03). Conclusion According to MR and SMR analysis, higher levels of TRAIL increased the risk of SVS by upregulating gene expression of KNG1 in brain cortex tissues. In addition, protective effects of E‐selectin and IL‐3a levels on WMPVS were regulated by increased DNA methylation of gene ABO in blood tissue.

ObjectivesAstragaloside IV (AS-IV) is a natural triterpenoid saponin compound with a variety of pharmacological effects, and several studies have clarified its anti-inflammatory effects, which may make it an effective alternative treatment against inflammation. In the study, we aimed to investigate whether AS-IV could attenuate the inflammatory response to acute lung injury and its mechanisms.MethodsDifferent doses of AS-IV (20mg·kg-1, 40mg·kg-1, and 80mg·kg-1) were administered to the ALI rat model, followed by collection of serum and broncho alveolar lavage fluid (BALF) for examination of the inflammatory response, and HE staining of the lung and colon tissues, and interpretation of the potential molecular mechanisms by quantitative real-time PCR (qRT-PCR), Western blotting (WB). In addition, fecal samples from ALI rats were collected and analyzed by 16S rRNA sequencing.ResultsAS-IV decreased the levels of TNF-α, IL-6, and IL-1β in serum and BALF of mice with Acute lung injury (ALI). Lung and colon histopathology confirmed that AS-IV alleviated inflammatory infiltration, tissue edema, and structural changes. qRT-PCR and WB showed that AS-IV mainly improved inflammation by inhibiting the expression of PI3K, AKT and mTOR mRNA, and improved the disorder of intestinal microflora by increasing the number of beneficial bacteria and reducing the number of harmful bacteria.ConclusionAS-IV reduces the expression of inflammatory factors by inhibiting the PI3K/AKT/mTOR pathway and optimizes the composition of the gut microflora in AIL rats.

Emerging evidence has demonstrated that ubiquitin conjugating enzyme E2 J1 (UBE2J1) exerts pivotal function in many cancers. UBE2J1 was reported to be dysregulated in endometrial cancer (EC). This study was designed to further investigate the regulatory character and mechanism of UBE2J1 in EC. Bioinformatic tools and databases were used to analyze gene expression pattern and gene expression correlation in EC tissues, and the prognosis of EC patients. Gene expression was evaluated by reverse-transcription quantitative polymerase chain reaction. Western blot was used for protein level detection. In vitro cell apoptosis was detected by flow cytometry analyses and TUNEL assays. In vivo cell apoptosis was evaluated by detecting Bax and Bcl-2 expression in tumor tissues via immunohistochemical and western blot analyses. In this study, UBE2J1 knockdown promoted cell apoptosis in EC cells and in mouse models of EC. PI3K and AKT expression is positively correlated with UBE2J1 level and is related to poor prognosis of EC patients. UBE2J1 knockdown repressed the PI3K/AKT pathway both in vitro and in vivo. UBE2J1 downregulation decreased MDM2 expression, but increased p53 expression. MDM2 overexpression reverses the promotion of UBE2J1 knockdown on cell apoptosis in EC. Overall, UBE2J1 knockdown induces cell apoptosis in EC by inactivating the PI3K/AKT signaling and suppressing the MDM2/p53 signaling.