Search

Abstract Background Intercropping increases land use efficiency and farmland ecological diversity. However, little is understood about whether and how soil biota, metabolites, and nutrients change under interspecific competition among plants. Thus, this study aimed to explore the changes in the physicochemical properties, microbial communities, and metabolites of rhizosphere and bulk soils of pepper monocropping and pepper–maize intercropping systems. Results Intercropping significantly increased the contents of available phosphorus (AP) and available potassium (AK), and decreased the pH value, whereas it had little effect on the total nitrogen (TN) and organic matter (OM) in the rhizosphere and bulk soils, compared with those in monocropping pepper. Moreover, the OM content was higher in rhizosphere soil than in bulk soil. The microbial community structures and metabolite profiles also differed between the two systems. The diversity of bacteria and fungi increased in intercropped pepper. The relative abundances of Actinobacteria, Chloroflexi, Cyanobacteria, and Ascomycota were higher while those of Proteobacteria, Planctomycetes, Mucoromycota, and Basidiomycota were significantly lower in the rhizosphere and bulk soils from the intercropping system than in those from the monocropping system. Linear discriminant analysis revealed that the predominant bacteria and fungi in the rhizosphere soil from the intercropping system belonged to the order Sphingomonadales and genera Nitrospira, Phycicoccus and Auricularia, whereas those in the bulk soil from the intercropping system belonged to the phylum Acidobacteria and genera Calocera, Pseudogymnoascus, and Trichosporon. Intercropping promoted the secretion of flavonoids, alkaloids, and nucleotides and their derivatives in the rhizosphere soil and significantly increased the contents of organoheterocyclic compounds in the bulk soil. Furthermore, the AP and AK contents, and pH value had strong positive correlations with bacteria. In addition, co-occurrence network analysis also showed that asebogenin, trachelanthamidine, 5-methyldeoxycytidine, and soil pH were the key factors mediating root-soil-microbe interactions. Conclusion Intercropping can alter microbial community structures and soil metabolite composition in rhizosphere and bulk soils, enhancing soil nutrient contents, enriching soil beneficial microbes and secondary metabolites (flavonoids and alkaloids) of intercropped pepper, and provided a scientific basis for sustainable development in the pepper-maize intercropping system.

Abstract Background Complex perianal fistulas, challenging to treat and prone to recurrence, often require surgical intervention that may cause fecal incontinence and lower quality of life due to large surgical wounds and potential sphincter damage. Human umbilical cord-derived MSCs (hUC-MSCs) and their exosomes (hUCMSCs-Exo) may promote wound healing. Methods This study assessed the efficacy, mechanisms, and safety of these exosomes in treating complex perianal fistulas in SD rats. We established a rat model, divided rats with fistulas into the control and the exosome groups. We assessed treatment efficacy through ultrasound, clinical observations, and histopathological analysis. We also evaluated the activation of the HIF-1α/TGF-β/Smad signaling pathway via PCR and Western blot and assessed serological markers for HIF-1α and inflammatory indices through ELISA. We analyzed gut microbiota and the systemic metabolic environment via untargeted metabolomics. Results The hUCMSCs-Exo effectively promoted healing of wound, regulated the immune balance enhanced collagen synthesis and angiogenesis in the perianal fistulas model of rats, and regulated the gut microbiota and metabolomic profiles. Results of PCR and Western blot analyses indicated that the exosomes activated HIF-1α/TGF-β/Smad signaling pathways. To the dosages tested, the 10ug/100ul concentration (medium dose) was found to be the most effective to the treatment of complex perianal fistulas. Conclusions The hUCMSCs-Exo significantly promoted the healing of wound in perianal fistulas of rats and demonstrated higher safety. The underlying mechanism facilitating the healing process was likely associated with the activation of the HIF-1α/TGF-β/Smad signaling pathway. Graphical abstract

Abstract Background Solutions to global health challenges depend on nations’ capacity for cross-disciplinary research in global health. Despite longstanding demands for practical guidelines, published guidance and frameworks for evaluating cross-disciplinary research are scarce and scattered among disciplines. We aimed to bring together information on how cross-disciplinary research has been evaluated and collate the frameworks and tools that have been used to advance knowledge and practice about the design and evaluation of cross-disciplinary research in global health. Methods We conducted a systematic scoping review by searching five databases (MEDLINE, CINAHL COMPLETE, Global Health, PubMed, Web of Science) for publications relevant for our objectives. These were to understand the characteristics of frameworks used to evaluate cross-disciplinary research, to describe how they had been used in practice, and to identify underlying common underpinning criteria. Our inclusion criteria were that the publications (a) focus on frameworks for cross-disciplinary research and (b) include aspects of evaluation or monitoring. The last search was conducted in July 2023. Results Thirty-one of 2718 screened publications met our inclusion criteria. The intended users of the frameworks were cross-disciplinary researchers (31; 97%), funders (15; 48%), evaluators/reviewers (15; 48%) and practitioners/stakeholders (10; 32%). Eight frameworks (26%) were bespoke for a particular project and used a ‘context-process-outcome’ approach to incorporate the whole research pathway. Four frameworks (13%) focused on evaluating outcome/impact. Nineteen (61%) focused on other specific aspects of cross-disciplinary research. Seventeen frameworks (55%) provided evaluation tools and 14 (45%) included guidance about their use in practice. Twenty-four (77%) provided examples of how their frameworks were used in practice, and 21 (68%) stated that their frameworks were generalizable in different contexts. The criteria used for the evaluations across the publications fell into four categories: appropriate cross-disciplinary research approaches for the project goal; shared learning and integration; meeting disciplinary standards; and effective synthesis. Conclusions Our collation and description of the heterogenous published guidance and frameworks for evaluating cross-disciplinary research, and our practical lessons for how to improve the robustness of such evaluations, will help funders, researchers and evaluators to make evidence-informed choices when they commission, design and evaluate cross-disciplinary research programmes in global health.

Abstract Background The increasing incidence of childhood obesity annually has led to a surge in physical and mental health risks, making it a significant global public health concern. This study aimed to discover novel biomarkers of childhood simple obesity through integrative multi-omics analysis, uncovering their potential connections and providing fresh research directions for the complex pathogenesis and treatment strategies. Methods Transcriptome, untargeted metabolome, and 16 S rDNA sequencing were conducted on subjects to examine transcripts, metabolites in blood, and gut microflora in stool. Results Transcriptomic analysis identified 599 differentially expressed genes (DEGs), of which 25 were immune-related genes, and participated in immune pathways such as antimicrobial peptides, neutrophil degranulation, and interferons. The optimal random forest model based on these genes exhibited an AUC of 0.844. The metabolomic analysis examined 71 differentially expressed metabolites (DEMs), including 12 immune-related metabolites. Notably, lauric acid showed an extremely strong positive correlation with BMI and showed a good discriminative power for obesity (AUC = 0.82). DEMs were found to be significantly enriched in four metabolic pathways, namely “Aminoacyl-tRNA biosynthesis”, “Valine leucine and isoleucine biosynthesis, and Glycine”, “Serine and threonine metabolism”, and “Biosynthesis of unsaturated fatty acids”. Microbiome analysis revealed 12 differential gut microbiotas (DGMs) at the phylum and genus levels, with p_Firmicutes dominating in the obese group and g_Escherichia-Shigella in the normal group. Subsequently, a Random Forest model was developed based on the DEMs, immune-related DEGs, and metabolites with an AUC value of 0.912. The 14 indicators identified by this model could potentially serve as a set of biomarkers for obesity. The analysis of the inter-omics correlation network found 233 pairs of significant correlations. DEGs BPIFA1, BPI, and SAA1, DEMs Dimethy(tetradecyl)amine, Deoxycholic acid, Pathalic anhydride, and DL-Alanine, and DGMs g_Intestinimonas and g_Turicibacter showed strong connectivity within the network, constituting a large proportion of interactions. Conclusion This study presents the first comprehensive description of the multi-omics characteristics of childhood simple obesity, recognizing promising biomarkers. Immune-related markers offer a new perspective for researching the immunological mechanisms underlying obesity and its associated complications. The revealed interactions among these biomarkers contribute to a deeper understanding the intricate biological regulatory networks associated with obesity.

Abstract Objectives To investigate the feasibility and effectiveness of a deep learning (DL) super-resolution (SR) ultrasound image reconstruction model for predicting cervical lymph node status in patients with papillary thyroid carcinoma(PTC). Methods In this retrospective study, researchers recruited 544 patients with PTC and randomly assigned them to training and test sets. SR ultrasound images were acquired using SR technology to improve image resolution, and artificial features and DL features were extracted from the original (OR) and SR images, respectively, to construct a ML, DL model. The best model was selected and aggregated with clinical parameters to construct the nomogram. The performance of the model is evaluated by ROC curves, calibration curves and decision curves. Results In distinguishing the presence or absence of metastatic lymph nodes, the predictive performance of the SR_ResNet 101 and SR_SVM models based on SR outperformed those based on OR. In the test set, SR_SVM AUC was 0.878 (95% CI 0.8203–0.9358), accuracy 0.854, while OR_SVM AUC was 0.822 (95% CI 0.7500–0.8937), accuracy 0.665. SR_ResNet 101 AUC was 0.799 (95% CI 0.7175–0.8806), accuracy 0.793, and OR_ResNet101 AUC was 0.751 (95% CI 0.6620–0.8401), accuracy 0.713. Subsequently, Nomogram_A and Nomogram_B were constructed by integrating the SR_SVM model and SR_ResNet 101 model, respectively, with clinical parameters, while Nomogram_C was constructed solely based on clinical indicators. In the test set, Nomogram_A demonstrated the best performance with an AUC of 0.930 (95% CI 0.8913–0.9682) and accuracy was 0.829. Nomogram_B AUC 0.868 (95% CI 0.8102–0.9261) and accuracy was 0.829, while Nomogram_C AUC 0.880 (95% CI 0.8257–0.9349) and accuracy was 0.787. The DeLong test revealed that the diagnostic performance of Nomogram_A based on SR_SVM was significantly higher than that of Nomogram_B, Nomogram_C, and the level of Radiologist (P

Abstract Background Studies have emphasised the adverse effects of poor sleep on human health, however, the correlation between sleep abnormalities and hypothyroidism remains unclear. This study evaluated whether sleep abnormalities may be related to increased prevalence of hypothyroidism in general US adults. Methods: In total, 9016 adults who participated in the National Health and Nutrition Examination Survey from 2007 to 2012 were analysed. A standardised questionnaire was used to collect data regarding sleep duration, self-reported trouble sleeping and sleep disorders. Values were assigned to the three aforementioned sleep factors, resulting in an overall sleep score of 0–3. The sleep patterns were divided into healthy sleep pattern (overall sleep score = 3), intermediate sleep pattern (overall sleep score = 2) and poor sleep pattern (overall sleep score = 0 or 1) according to a former study. Hypothyroidism was defined as thyroid-stimulating hormone (TSH) levels > 5.6 mIU/mL or the need to take thyroid hormones. Multivariable logistic regression analysis was performed to assess the relationship between sleep abnormalities and hypothyroidism. Results: The overall prevalence of hypothyroidism was 8.0% among the 9016 participants. Self-reported trouble sleeping (odds ratio [OR] = 1.38, 95% CI: 1.14–1.68, p = 0.001) and sleep disorders (OR = 1.40, 95% CI: 1.06–1.86, p = 0.0196) were associated with increased prevalence of hypothyroidism. Neither short sleep duration (OR = 0.99, 95% CI: 0.82–1.19) nor long sleep duration (OR = 0.98, 95% CI: 0.61–1.58) was significantly associated with hypothyroidism. Moreover, poor sleep pattern was significantly associated with increased prevalence of hypothyroidism (OR = 1.30, 95% CI: 1.03–1.66, p = 0.0301). Conclusions: Both trouble sleeping and sleep disorders were associated with increased prevalence of hypothyroidism.

Abstract Essential thrombocythemia (ET) is a myeloproliferative malignancy caused by the excessive proliferation of megakaryocytes in the bone marrow, resulting in the overproduction of peripheral platelets. ET can lead to thrombotic events, such as ischemic stroke (IS), though it is a rare cause of IS. Bilateral medial medullary infarction (BMMI), also known as “Y appearance” infarction due to its distinctive imaging morphology, is a rare clinical subtype of IS which typically has a poor prognosis and a high mortality rate. Herein, we report the case of a 43-year-old male with a history of ET. The patient’s platelet count was poorly controlled, and he did not receive regular treatment. After developing symptoms such as dizziness, dysphagia, choking on water, slurred speech, blurred vision, and bilateral limb numbness. Head magnetic resonance imaging revealed a “Y appearance” infarction in the bilateral medial medulla. After admission, the patient was administered intravenous antiplatelet therapy with tirofiban. However, when he was switched to oral aspirin after three days, he experienced decreased muscle strength and worsening symptoms. Therefore, tirofiban was continued for 14 days. Upon discharge, the patient experienced residual limb numbness. His National Institutes of Health Stroke Scale score was 1, Modified Rankin Scale score was 0, and platelet count had decreased to the normal range. During the 9-month follow-up period after discharge, the patient still had only mild limb numbness. Our report presents a special case of “Y appearance” infarction due to ET. Owing to fluctuations in the patient’s condition, he received long-term high-dose tirofiban, which ultimately led to a significant improvement in his symptoms.

Abstract Focused ultrasound ablation surgery (FUAS) is a minimally invasive treatment option that has been utilized in various tumors. However, its clinical advancement has been hindered by issues such as low safety and efficiency, single image guidance mode, and postoperative tumor residue. To address these limitations, this study aimed to develop a novel multi-functional gas-producing engineering bacteria biological targeting cooperative system. Pulse-focused ultrasound (PFUS) could adjust the ratio of thermal effect to non-thermal effect by adjusting the duty cycle, and improve the safety and effectiveness of treatment.The genetic modification of Escherichia coli (E.coli) involved the insertion of an acoustic reporter gene to encode gas vesicles (GVs), resulting in gas-producing E.coli (GVs-E.coli) capable of targeting tumor anoxia. GVs-E.coli colonized and proliferated within the tumor while the GVs facilitated ultrasound imaging and cooperative PFUS. Additionally, multifunctional cationic polyethyleneimine (PEI)-poly (lactic-co-glycolic acid) (PLGA) nanoparticles (PEI-PLGA/EPI/PFH@Fe3O4) containing superparamagnetic iron oxide (SPIO, Fe3O4), perfluorohexane (PFH), and epirubicin (EPI) were developed. These nanoparticles offered synergistic PFUS, supplementary chemotherapy, and multimodal imaging capabilities.GVs-E.coli effectively directed the PEI-PLGA/EPI/PFH@Fe3O4 to accumulate within the tumor target area by means of electrostatic adsorption, resulting in a synergistic therapeutic impact on tumor eradication.In conclusion, GVs-E.coli-mediated multi-functional nanoparticles can synergize with PFUS and chemotherapy to effectively treat tumors, overcoming the limitations of current FUAS therapy and improving safety and efficacy. This approach presents a promising new strategy for tumor therapy. Graphical Abstract

Abstract Immunodeficiency 11B with atopic dermatitis (IMD11B, OMIM:617638) is rare primary immunodeficiency disease caused by germline dominant negative (DN) mutations in the CARD11 gene. Affected patients present with immune dysfunction, recurrent infections and atopic dermatitis. In this study, we sought to identify and characterize the genetic variant in one patient with periodic fever, recurrent infections, and eczema. Trio whole-exome sequencing (WES) was employed in this patient and her parents, and Sanger sequencing validated the potential pathogenic variant. In vitro functional study was performed to evaluate the pathogenicity of genetic variant identified. A very rare missense mutation (c.2324C > T, p.S775L) in CARD11 gene (NM_032415) was identified by WES in the patient but not her parents. Luciferase reporter assays and co-immunoprecipitation demonstrated mutation exerts a dominant-interfering effect on wild-type CARD11, inhibiting the activity of NF-κB. RNA sequencing analysis also confirmed that mutant CARD11 inhibited down-stream transcriptional activity of NF-κB. A review of literature doesn’t found significant genotype–phenotype correlation. We identified a vary rare DN CARD11 mutation, expanding the genetic and phenotypic spectrum of CARD11.

Abstract Background Marchiafava-Bignami disease (MBD) is an exceptionally rare condition, a fact that should pique the professional curiosity of medical practitioners. In recent years, case reports of this disease have been infrequent, and no comprehensive analysis or summary of the characteristics of the published cases has been conducted. Methods We collected the medical records of three patients treated at our hospital from March 2022 to March 2023. Furthermore, we searched PubMed for “case reports” from January 2017 to March 2023 and included 30 cases. By retrospectively analyzing these 33 cases, we summarized the characteristics of the disease. Results Based on our analysis, we found that MBD primarily affects middle-aged men and typically has an acute or subacute onset, with the primary clinical manifestations being disturbances of consciousness, speech disorders, cognitive impairment, and psychiatric or behavioral abnormalities, often leading to misdiagnosis of psychiatric disorders. Most patients have a history of alcohol consumption or malnutrition. Head CT or MRI revealed symmetric lesions in the corpus callosum, with the splenium being the most commonly affected area. Lesions might also involve white matter outside the corpus callosum, and a wider range of lesions suggested a poor prognosis. However, the prognosis is generally favorable with timely and adequate administration of B vitamins, providing reassurance to medical professionals and patients alike. Conclusion The early recognition and treatment of Marchiafava-Bignami disease are paramount, as they can significantly improve the prognosis. This underscores the critical need for prompt clinical intervention in the early stages of the disease, instilling a sense of urgency and significance in the work of medical professionals.

BackgroundAlthough the immune response of host T cells to human immunodeficiency virus (HIV) significantly influences the progression of the infection, the development of T-cell-based vaccines and therapies, as well as the clinical evaluation of specific T-cell functions, is currently markedly hindered by the absence of broad-spectrum, functionally validated HIV T-cell epitopes that account for the polymorphisms of the human leukocyte antigen (HLA) within an indicated geographic population. This study aimed to identify T-cell epitopes derived from the GP160, GAG, and POL proteins of the HIV-1 strain, specifically linked to 12 prevalent HLA-A allotypes, that collectively represent approximately 91% of the total gene frequency in Northeast Asian populations.MethodsA total of 134 epitopes were predicted in silico and selected as potential candidates for further validation. Subsequently, peripheral blood mononuclear cells (PBMCs) were collected from 96 individuals with HIV-1 and cocultured ex vivo with each epitope candidate peptide, followed by the detection of activated CD8+ T cells. Peripheral blood mononuclear cells (PBMCs) were collected from 96 individuals with HIV-1 and cocultured ex vivo with each candidate peptide epitope, followed by the detection of activated CD8+ T cells. A total of 69 epitopes were validated as real-world HIV T-cell epitopes presented by 12 dominant HLA-A allotypes. Furthermore, the HLA-A cross-restriction for each epitope candidate was identified through peptide competitive binding assays using 12 transfected HMy2.CIR cell lines.ResultsA total of 45 epitopes demonstrated high affinity, while 31 epitopes displayed intermediate affinity. A broad-spectrum CD8+ T-cell epitope library containing 141 validated epitope peptides was used to universally detect HIV-1-specific CD8+ T cells via peptide-PBMC ex vivo coculture and intracellular IFN-γ staining. In 52 people with HIV-1, the number of reactive HIV-1 specific CD8+ T cells was significantly higher in the CD4+ T-cell-high patient group compared to the CD4+ T-cell-low patient group, and it correlated with the CD4+ T-cell-low patient group (

The application of face recognition technology in Library Access Control System (LACS) has an important impact on improving the security and management efficiency of the library. However, the traditional face recognition methods have some limitations in the face of complex environmental conditions such as illumination and posture change. To solve this problem, an improved method combining the Aggregating Spatial Embeddings for Face Recognition (ASEF) algorithm and Principal Component Analysis (PCA) is proposed. The PCA algorithm is optimized by introducing beta prior and full probability Bayesian model. In addition, the research also integrates K-means Clustering Algorithm (KA) to further improve the accuracy and efficiency of face recognition. The experiment showed that the improved PCA method had an average recognition rate of 92.6%, an average recognition speed of 0.40s, and higher accuracy compared to other related methods, reaching 96%. In practical applications, the system quickly and accurately completes the identification of personnel entry and exit, and improves the efficiency and security of library access management.

BackgroundKawasaki disease (KD), an acute self-limiting vasculitis, is the main cause of acquired heart disease. Timely diagnosis and treatment can mitigate the occurrence of complications and improve patient prognosis. Facial nerve paralysis (FNP) and ptosis are rare complications of KD and are rarely reported, but FNP is considered a high risk factor for coronary aneurysms. If giant coronary artery aneurysms are formed, clinicians should be vigilant when diagnosing the formation of systemic artery aneurysms (SAAs).Patient presentationA 10-month-old girl with fever, diffuse rash, and conjunctival congestion was hospitalized locally, diagnosed with KD, and treated with intravenous infusion of gamma globulin (IVIG). She had fever again after 1 week of temperature stability, accompanied by conjunctival congestion, and was treated with a second dose of IVIG, but she still experienced recurrent fever. The day prior to admission, she developed facial asymmetry, left FNP, diffuse erythema and membranous peeling of the fingers of both hands. The patient's body temperature normalized after treatment with 20 mg/kg methylprednisolone, but cardiac ultrasound revealed progressive enlargement of the coronary artery aneurysms. On day 37of the illness, transient eyelid ptosis developed; fortunately, the left FNP and eyelid ptosis finally resolved, leaving no sequelae. Two years and eight months after onset, the patient developed bilateral humeral aneurysm.ConclusionThis is the first KD patient involving two neurological complications combined with giant coronary artery aneurysms and SAAs. KD needs to be considered in infants with unexplained recurrent fever who present with FNP or ptosis. FNP secondary to KD is a high risk factor for coronary artery aneurysms, so it is necessary to perform cardiac ultrasound for accurate diagnosis. KDs combined with giant coronary aneurysms require careful physical examination and noninvasive angiography during follow-up to detect SAA formation.

Methylation modifications play pertinent roles in regulating gene expression and various biological processes. The silencing of the demethylase enzyme TET1 can affect the expressions of key oncogenes or tumour suppressor genes, thus contributing to tumour formation. Nonetheless, how TET1 affects the progression of cervical cancer is yet to be elucidated. In this study, we found that the expression of TET1 was significantly downregulated in cervical cancer tissues. Functionally, TET1 knockdown in cervical cancer cells can promote cell proliferation, migration, invasion, cervical xenograft tumour formation and EMT. On the contrary, its overexpression can reverse the aforementioned processes. Moreover, the autophagy level of cervical cancer cells can be enhanced after TET1 knockdown. Mechanistically, methylated DNA immunoprecipitation (MeDIP)-sequencing and MeDIP quantitative real-time PCR revealed that TET1 mediates the methylation of autophagy promoter regions. These findings suggest that TET1 affects the autophagy of cervical cancer cells by altering the methylation levels of NKRF or HIST1H2AK, but the specific mechanism needs to be investigated further.

Abstract Low-dose X-CT scanning method effectively reduces radiation hazards, however, reducing the radiation dose will introduce noise and artifacts during the projection process, resulting in a decrease in the quality of the reconstructed image. To address this problem, we combined 2D variational modal decomposition and dictionary learning. We proposed a low-dose CT (LDCT) image denoising algorithm based on an improved K-SVD algorithm with image decomposition. The dictionary obtained by K-SVD training lacks consideration of image structure information. To address this problem, we employ the two-dimensional variational mode decomposition (2D-VMD) method to decompose the image into distinct modal components. Through the adaptive learning of dictionaries based on the characteristics of each modal component, independent denoising processing is applied to each component, avoiding the loss of structural and detailed information in the image. In addition, we introduce the regularized orthogonal matching pursuit algorithm (ROMP) and dictionary atom optimization method to improve the sparse representation ability of the dictionary and reduce the impact of noise atoms on denoising performance. The experiments show that the proposed method outperforms other denoising methods regarding peak signal-to-noise ratio and structural similarity. The proposed method maintains the denoised image details and structural information while removing LDCT image noise and artifacts. The image quality after denoising is significantly improved and facilitates more accurate detection and analysis of lesion areas.

High-Temperature Aquifer Thermal Energy Storage (HT-ATES) system holds significant potential for addressing the challenges of energy supply and demand management. However, the complexity of natural fracture networks within reservoirs poses a challenge for accurate simulations. In this work, a coupled thermal-hydraulic-mechanical (THM) model was developed to investigate the performance of HT-ATES system in naturally fractured reservoirs. The developed THM model was validated against analytical solutions, achieving mean errors of less than 4 %. The effects of varying parameters on heat recovery efficiency of HT-ATES system were examined. The results demonstrated that fracture number was the most influential factor on system performance, causing a variation in heat recovery efficiency of 38.58 %. More importantly, XGBoost algorithm was integrated with THM model to develop a surrogate model, which enabled the accurate regression prediction of the bottom-hole temperature/pressure evolutions as well as heat recovery efficiency, with five selected evaluation metrics demonstrating good performance, such as R2 >0.99 and MAPE

The fat mass and obesity-associated protein (FTO) is identified as regulating mammalian development and diseases by removing methyl groups from RNAs. However, the roles of FTO in the context of oral lichen planus (OLP) remain unknown. Here, we demonstrated that the protein levels of FTO in the keratinocytes from OLP patients were down-regulated compared to those from healthy participants. At the molecular level, we explained that GSK-3β-induced phosphorylation promoted FTO protein degradation in diseased oral keratinocytes. Using a cell co-culture model, we further confirmed that FTO deficiency facilitated NF-κB activation and apoptosis in oral keratinocytes under inflammatory conditions. Vitamin D receptor (VDR), which plays a protective role in OLP, was mediated by FTO in an RNA N6-methyladenosine (m6A) methylation-dependent way. FTO overexpression failed to suppress NF-κB and caspase-3 activities upon VDR ablation in oral keratinocytes, suggesting that FTO insufficiency damages oral epithelial by targeting VDR. Collectively, these data reveal that FTO deficiency facilitates epithelial dysfunction in OLP by decreasing VDR expression.

With the rapid development of the artificial intelligence (AI) technology, its application in optimizing heating, ventilation and air-conditioning (HVAC) systems operation is becoming increasingly widespread. This study reviews the latest advances in AI optimization for HVAC systems operation, systematically outlining the characteristics of the AI technology and its various application methods in air conditioning systems. The main features of the AI technology are first introduced. The main algorithms of supervised learning, reinforcement learning, and deep learning are then analyzed in the fields of air conditioning operation optimization, energy consumption prediction and control, indoor environmental protection, and fault detection and diagnosis. The combination of the AI and digital twin technologies is also explored. This review study focuses on the intelligent control technology, multi-objective optimization of system operation, system optimization based on occupant behavior and thermal comfort, and system fault detection and diagnosis. Although the AI technology has led to satisfactory results in air conditioning system optimization, its practical applications still face challenges, such as the model accuracy and generalization ability, applicability, and integration with existing systems. The analysis conducted in this paper provides a foundation for the optimization of HVAC system operation.

In the study, quercus infectoria gall (QIG) was used to develop a pH/thermosensitive gel in situ delivery system for enema administration of to treat acute ulcerative colitis (UC). The QIG ethanol extract pH/temperature-sensitive gel (QIG-pH-TSG) was characterized by using DSC, SEM, rheological and drug release analyses. The therapeutic effect in UC mice of the obtained gel were studied. The gel was maintained in a flowing liquid state under nonphysiological conditions (25 °C) to facilitate drug administration, and was transformed into a pseudoplastic liquid state under physiological conditions (37 °C), which prolonged its retention time in the colon. The gel drug was completely released within 24 h, and the temperature and viscosity of the gel were within the required range. In the in vitro anti-inflammatory test, QIG-pH-TSG decreased the level of TNF-α and IL-6, and increased IL-10 in RAW 264.7 actived by LPS. Moreover, the administration of QIG-pH-TSG resulted in a decrease in the colon histopathological score and an increase in colonic length, and also could reduce the IL-6, TNF-α, and C-reactive protein (CRP) levels in UC mice along with significant increases in IL-10 level in the colon. The QIG-pH-TSG could increase the concentration of QIG at the local inflammatory site and lead to an effective repair of the colonic mucosa. Therefore, the pH/thermosensitive in situ gel may serve as a drug delivery system for QIG to treat UC and overcome the limitations of some existing formulations. These results indicated that this composite gel was effectively in UC mice and the study provided a practical reference for the application of QIG-pH-TSG in the treatment of UC.

The Ordos Basin is a large cratonic basin with stable deposition in Northwest China. Given its mostly stable subsidence background and the urgent need for saline water disposal and carbon dioxide storage in the coal mining and coal chemical industries, the Ordos Basin has been chosen as a pilot demonstration site for carbon dioxide and saline water storage in China. However, few studies have been made to evaluate the sedimentary and sequence stratigraphy characteristics of this region, as well as their influence on carbon dioxide and saline water storage potential. To address this research gap, we conducted a sedimentary study of the Lower Triassic Liujiagou Formation in the northeastern Ordos Basin utilizing the stratigraphy theory, laboratory test analysis, and pilot project demonstration, to evaluate the area's viability for the deep geological storage of gas and liquid waste. We studied the tectonic setting, petrological features, and sedimentary characteristics of the favorable strata and predicted favorable areas based on sequence stratigraphy theory. The lithology predominantly consists of feldspathic graywacke, with a fine grain size and mostly fine-to-medium-grained sandstone. The distribution of thick-grained sandstone and fine-grained sediment was identified by dividing the sequence, and a favorable reservoir-cap assemblage configuration was formed. It's concluded that the Lower Triassic Liujiagou Formation exhibits suitable characteristics for the deep geological storage of carbon dioxide and saline water. This study demonstrates the importance of basic theory in guiding practical applications and provides a reference for the scientific selection of favorable areas for deep basin storage.

Abstract Geothermal energy is a sustainable energy source that meets the needs of the climate crisis and global warming caused by fossil fuel burning. Geothermal resources are found in complex geological settings, with faults and interconnected networks of fractures acting as pathways for fluid circulation. Identifying faults and fractures is an essential component of exploiting geothermal resources. However, accurately predicting fractures without high-resolution geophysical logs (e.g., image logs) and well-core samples is challenging. Soft computing techniques, such as machine learning, make it possible to map fracture networks at a finer resolution. This study employed four supervised machine learning techniques (multilayer perceptron (MLP), random forests (RF), extreme gradient boosting (XGBoost), and support vector regression (SVR)) to identify fractures in geothermal carbonate reservoirs in the sub-basins of East China. The models were trained and tested on a diverse well-logging dataset collected at the field scale. A comparison of the predicted results revealed that XGBoost with optimized hyperparameters and data division achieved the best performance than RF, MLP, and SVR with RMSE = 0.02 and R2 = 0.92. The Q-learning algorithm outperformed grid search, Bayesian, and ant colony optimizations. The blind well test demonstrates that it is possible to accurately identify fractures by applying machine learning algorithms to standard well logs. In addition, the comparative analysis indicates that XGBoost was able to handle the complex relationship between input parameters (e.g., DTP > RD > DEN > GR > CAL > RS > U > CNL) and fracture in geologically complex geothermal carbonate reservoirs. Furthermore, comparing the XGBoost model with previous studies proved superior in training and testing. This study suggests that XGBoost with Q-learning-based optimized hyperparameters and data division is a suitable algorithm for identifying fractures using well-log data to explore complex geothermal systems in carbonate rocks. Graphical abstract

Abstract Background Gestational diabetes mellitus (GDM) is one of the most common metabolic disorders during pregnancy and is associated with adverse outcomes in both mothers and their children. After delivery, women who experience GDM are also at higher risk of both subsequent GDM and type 2 diabetes mellitus (T2DM) than those who do not. Therefore, healthcare providers and public health practitioners need to develop targeted and effective interventions for GDM. In this study, we aimed to explore the perceptions regarding health behaviors and related factors during the inter-pregnancy period among Chinese women with a history of GDM through the lens of the theory of planned behavior (TPB). Methods Between December 2021 and September 2022, 16 pregnant Chinese women with a history of GDM were purposively recruited from a tertiary maternity hospital in Shanghai for face-to-face semi-structured interviews. They were asked questions regarding their health behaviors and related factors. The transcribed data were analyzed using a directed qualitative content analysis method based on the theory of TPB. Results The health-related behaviors of the women varied substantially. We identified five domains that influenced women’s behaviors according to TPB constructs and based on the data collected: behavioral attitude (perceived benefits of healthy behaviors and the relationship between experience and attitude towards the oral glucose tolerance testing); subjective norms (influences of significant others and traditional cultural beliefs); perceived behavior control (knowledge of the disease, multiple-role conflict, the impact of COVID-19, an unfriendly external environment and difficulty adhering to healthy diets), incentive mechanisms (self-reward and external incentives); preferences of professional and institutional support (making full use of social media platform and providing continuous health management). Conclusions The health-related behaviors of women with a history of GDM were found to be affected by multiple factors. Healthcare professionals are recommended to provide women with sufficient information regarding the disease and to take advantage of the power of the family and other social support networks to improve women’s subjective norms and to promote the adoption of a healthy lifestyle.

Abstract Background Acute myocardial infarction (AMI) and diabetic nephropathy (DN) are common clinical co-morbidities, but they are challenging to manage and have poor prognoses. There is no research on the bioinformatics mechanisms of comorbidity, and this study aims to investigate such mechanisms. Methods We downloaded the AMI data (GSE66360) and DN datasets (GSE30528 and GSE30529) from the Gene Expression Omnibus (GEO) platform. The GSE66360 dataset was divided into two parts: the training set and the validation set, and GSE30529 was used as the training set and GSE30528 as the validation set. After identifying the common differentially expressed genes (DEGs) in AMI and DN in the training set, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses and protein–protein interaction (PPI) network construction were performed. A sub-network graph was constructed by MCODE, and 15 hub genes were screened by the Cytohubba plugin. The screened hub genes were validated, and the 15 screened hub genes were subjected to GO, KEGG, Gene MANIA analysis, and transcription factor (TF) prediction. Finally, we performed TF differential analysis, enrichment analysis, and TF and gene regulatory network construction. Results A total of 46 genes (43 up-regulated and 3 down-regulated) were identified for subsequent analysis. GO functional analysis emphasized the presence of genes mainly in the vesicle membrane and secretory granule membrane involved in antigen processing and presentation, lipopeptide binding, NAD + nucleosidase activity, and Toll-like receptor binding. The KEGG pathways analyzed were mainly in the phagosome, neutrophil extracellular trap formation, natural killer cell-mediated cytotoxicity, apoptosis, Fc gamma R-mediated phagocytosis, and Toll-like receptor signaling pathways. Eight co-expressed hub genes were identified and validated, namely TLR2, FCER1G, CD163, CTSS, CLEC4A, IGSF6, NCF2, and MS4A6A. Three transcription factors were identified and validated in AMI, namely NFKB1, HIF1A, and SPI1. Conclusions Our study reveals the common pathogenesis of AMI and DN. These common pathways and hub genes may provide new ideas for further mechanistic studies.

Abstract The aging process of the kidneys is accompanied with several structural diseases. Abnormal fiber formation disrupts the balance of kidney structure and function, causing to end-stage renal disease and subsequent renal failure. Despite this, the precise mechanism underlying renal damage in aging remains elusive. In this study, ABI3BP gene knockout mice were used to investigate the role of ABI3BP in renal aging induced by irradiation. The results revealed a significant increase in ABI3BP expression in HK2 cells and kidney tissue of aging mice, with ABI3BP gene knockout demonstrating a mitigating effect on radiation-induced cell aging. Furthermore, the study observed a marked decrease in Klotho levels and an increase in ferroptosis in renal tissue and HK2 cells following irradiation. Notably, ABI3BP gene knockout not only elevated Klotho expression but also reduced ferroptosis levels. A significant negative correlation between ABI3BP and Klotho was established. Further experiments demonstrated that Klotho knockdown alleviated the aging inhibition caused by ABI3BP downregulation. This study identifies the upregulation of ABI3BP in aged renal tubular epithelial cells, indicating a role in promoting ferroptosis and inducing renal aging by inhibiting Klotho expression.

Magnesium (Mg) is abundant in humans. Studies have shown that Mg2+ significantly affects physiological processes such as osteogenesis, osteoblast adhesion and motility, immunomodulation, and angiogenesis. Mg-based alloy porous scaffolds have attracted increasing attention because of their degradability and mechanical properties. Hence, wire-cut EDM was used to fabricate porous scaffolds. In addition, fluoride treatment afforded an MgF2 coating, and racemic polylactic acid PDLLA was used as the carrier of rhBMP-2, which was evenly coated on the surface of the passivated porous alloy scaffold to slowly release growth factors and slow down the degradation rate. The rat femoral condyle defect model experiment was performed to study the in vivo bone regeneration capacity of porous scaffolds and compare the differences in the healing effect with or without rhBMP-2. The enhanced corrosion resistance of the porous scaffold was confirmed through in vitro immersion experiments. Micro-CT implied that porous scaffold with rhBMP-2 induced new bone formation and the new bone formation along the pores, as well as the histological examination in vivo. In summary, the porous scaffold promotes bone formation and has great potential for clinical translation.

Abstract Background Doxorubicin (Dox) is associated with various liver injuries, limiting its clinical utility. This study investigates whether NSUN2 participates in Dox-induced liver injury and the associated molecular mechanism. Methods In vivo and in vitro liver cell injury models were constructed based on Dox therapy. The protein levels of NSUN2 and oxidative stress indicators Nrf2, HO-1, and NQO1 were evaluated by Western blot. The RNA binding potential was detected by RNA methylation immunoprecipitation (RIP). Additionally, the effect of NSUN2 on Nrf2 mRNA synthesis and localization was evaluated using an RNA fluorescence probe. Results NSUN2 was downregulated, and liver tissue suffered significant pathological damage in the Dox group. The levels of ALT and AST significantly increased. NSUN2 interference exacerbated Dox-induced liver cell damage, which was reversed by NSUN2 overexpression. RIP demonstrated that NSUN2 recognized and bound to Nrf2 mRNA. Western blot analysis showed the protein level of Nrf2 in the NSUN2-WT group was significantly higher than that of the control group, whereas there was no significant change in Nrf2 level in the mutant NSUN2 group. Luciferase analysis demonstrated that NSUN2 could recognize and activate the Nrf2 5′UTR region of LO2 cells. In addition, RIP analysis revealed that ALYREF could recognize and bind to Nrf2 mRNA and that ALYREF controls the regulatory effect of NSUN2 on Nrf2. Conclusion NSUN2 regulates Dox-induced liver cell damage by increasing Nrf2 mRNA m5C methylation to inhibit inhibiting antioxidant stress. The regulatory effect of NSUN2 on Nrf2 depends on ALYREF.

Abstract Background The clinical routine test of HBV-specific T cell reactivity is still limited due to the high polymorphisms of human leukocyte antigens (HLA) in patient cohort and the lack of universal detection kit, thus the clinical implication remains disputed. Methods A broad-spectrum peptide library, which consists of 103 functionally validated CD8+ T-cell epitopes spanning overall HBsAg, HBeAg, HBx and HBpol proteins and fits to the HLA polymorphisms of Chinese and Northeast Asian populations, was grouped into eight peptide pools and was used to establish an ELISpot assay for enumerating the reactive HBV-specific T cells in PBMCs. Totally 294 HBV-infected patients including 203 ones with chronic hepatitis B (CHB), 13 ones in acute resolved stage (R), 52 ones with liver cirrhosis (LC) and 26 ones with hepatocellular carcinoma (HCC) were detected, and 33 CHB patients were longitudinally monitored for 3 times with an interval of 3–5 months. Results The numbers of reactive HBV-specific T cells were significantly correlated with ALT level, HBsAg level, and disease stage (R, CHB, LC and HCC), and R patients displayed the strongest HBV-specific T cell reactivity while CHB patients showed the weakest one. For 203 CHB patients, the numbers of reactive HBV-specific T cells presented a significantly declined trend when the serum viral DNA load, HBsAg, HBeAg or ALT level gradually increased, but only a very low negative correlation coefficient was defined (r = − 0.21, − 0.21, − 0.27, − 0.079, respectively). Different Nucleotide Analogs (NUCs) did not bring difference on HBV-specific T cell reactivity in the same duration of treatment. NUCs/pegIFN-α combination led to much more reactive HBV-specific T cells than NUCs monotherapy. The dynamic numbers of reactive HBV-specific T cells were obviously increasing in most CHB patients undergoing routine treatment, and the longitudinal trend possess a high predictive power for the hepatitis progression 6 or 12 months later. Conclusion The presented method could be developed into an efficient reference method for the clinical evaluation of cellular immunity. The CHB patients presenting low reactivity of HBV-specific T cells have a worse prognosis for hepatitis progression and should be treated using pegIFN-α to improve host T-cell immunity.

Abstract Although intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) presents with persistent inflammatory stimulation of the blood vessels and an increased risk of coronary artery dilatation. However, the pathogenesis of this disease is unclear, with no established biomarkers to predict its occurrence. This study intends to explore the utility of S100A12/TLR2-related signaling molecules and clinical indicators in the predictive modeling of IVIG-resistant KD. The subjects were classified according to IVIG treatment response: 206 patients in an IVIG-sensitive KD group and 49 in an IVIG-resistant KD group. Real-time PCR was used to measure the expression of S100A12, TLR2, MYD88, and NF-κB in peripheral blood mononuclear cells of patients, while collecting demographic characteristics, clinical manifestations, and laboratory test results of KD children. Multi-factor binary logistic regression analysis identified procalcitonin (PCT) level (≥ 0.845 ng/mL), Na level (≤ 136.55 mmol/L), and the relative expression level of S100A12 (≥ 10.224) as independent risk factors for IVIG-resistant KD and developed a new scoring model with good predictive ability to predict the occurrence of IVIG-resistant KD.

Objective To study the role of 1,25(OH)2D3 in cutaneous wound healing and the underlying mechanisms in mice. Methods Forty 5-week-old male C57BL/6 mice were randomly divided into 5 groups, i.e., wound, wound + vitamin D receptor (VDR) inhibitor, wound+vitamin D receptor (VDR) agonist, wound +vitamin D (VD) powder and normal controls. The wound healing rates were calculated according the photographs of wound size taken at different time points. At the 9th day of wound, ELISA was used to measure serum levels of 1,25(OH)2D3. In addition, wound edge tissue was taken for HE staining and immunohistochemical staining of VDR and CD31. Finally, expression levels of both mRNA and proteins for VDR, Notch1, TNF-α, IL-17A, IL-17F and IL-22 were assessed using real-time quantitative PCR and Western Blot, respectively. Results At the 9th day of wound, the levels of serum 1,25(OH)2D3 and cutaneous VDR and CD31 expression were decreased, while expression levels of TNF-α, IL-17A, IL-17F and IL-22 were increased in the wounded skin compared to the normal controls (P0.05). Compared with the untreated wounded skin, treatments with either VDR agonist or VD powder significantly increased wound healing rate, serum 1,25(OH)2D3 levels and expression levels of cutaneous VDR, CD31 and Notch1, while decreasing cutaneous TNF-α, IL-17A, IL-17F and IL-22 expression (P

The skin wound healing is a complex physiological process involving coagulation, inflammation, proliferation, and remodeling. Innate immune cells play a crucial role in regulating signaling factors during skin wound healing. Due to their unique tissue distribution and origin, innate lymphoid cells 3 (ILC3), a member of innate immune cells, have the potential to regulate the wound healing process. They can secrete multiple cytokines, such as IL-17, IL-22, and GM-CSF, to maintain skin homeostasis, promote keratinocyte proliferation and epithelial cell migration, and participate in wound tissue reconstruction. The function of ILC3 is regulated by various signaling pathways, including RA-RAR, FFAR2, vitamin D receptor, DR3, and AhR, making them potential integrators of microenvironment around the wound. Numerous studies suggest the importance of ILC3 in skin wound healing, making them a potential therapeutic target in wound healing. This article comprehensively reviews the origin, tissue distribution, function, and signaling receptors of ILC3 and summarizes recent advances in the study of ILC3 in skin wound healing.

Summary: Systemic sclerosis (SSc) is an autoimmune disease affecting multiple tissues. The underlying causes and mechanisms of subcutaneous adipose tissue (SAT) loss in SSc remain unclear. Recent studies have highlighted the role of microRNAs in adipogenesis. Our study found that miR-4769-3p was upregulated in SSc patients and its silencing promoted SAT recovery in bleomycin-induced SSc mice, suggesting that miR-4769-3p might affect adipogenesis in SSc. Manipulating miR-4769-3p expression in 3T3-L1 cells revealed that its inhibition enhanced adipogenesis, while its overexpression weakened it. Further investigations showed that miR-4769-3p bound to 3′UTR of ubiquitin-specific protease-18 (USP18), inhibiting its expression, while USP18 interacted with voltage-dependent anion channel-2 (VDAC2), both of which were reduced in SSc. Silencing either USP18 or VDAC2 attenuated adipogenesis. Notably, USP18 inhibited VDAC2 ubiquitination and degradation, whereas miR-4769-3p reversed the VDAC2-induced elevation of adipogenesis, suggesting that miR-4769-3p inhibited adipogenesis by negatively regulating the USP18/VDAC2 pathway, providing a potential therapeutic target for SSc.

Vehicle exhaust is one of the major organic sources in urban areas. Old taxis equipped with failed three-way catalysts (TWCs) have been regarded as “super emitters”. Compressed natural gas (CNG) is a regular substitution fuel for gasoline in taxis. The relative effect of fuel substitution and TWC failure has not been thoroughly investigated. In this work, vehicle exhausts from gasoline and CNG taxis with optimally functioning and malfunctioning TWCs are sampled by Tenax TA tubes and then analyzed by a comprehensive two-dimensional gas chromatography-mass spectrometer (GC×GC–MS). A total of 216 organics are quantified, including 80 volatile organic compounds (VOCs) and 132 intermediate volatility organic compounds (IVOCs). Failure of TWC introduces super emitters with 30 – 70 times emission factors (EFs), 60 – 112 times ozone formation potentials (OFPs), and 34 – 92 times secondary organic aerosols (SOAs) more than normal vehicles. Specifically, for the taxi with failed TWC, the total organic EF of CNG is 16 times that of gasoline, indicating that the failure of TWC exceeds the emission reduction achieved by CNG-gasoline substitution. A significant but unbalanced reduction of ozone and SOA is observed after TWC, whereas a notable “enrichment” in IVOCs was observed. Naphthalene is a typical IVOC component strongly associated with CNG-gasoline substitution and TWC failure, which is lacking in current VOC measurement. We especially emphasize that there is an urgent need to scrap vehicles with failed TWCs in order to significantly reduce air pollution.

Gonadal and gonosomal mosaicism describe phenomena in which a seemingly healthy individual carries a genetic variant in a subset of their gonadal tissue or gonadal and somatic tissue(s), respectively, with risk of transmitting the variant to their offspring. In families with one or more affected offspring, occurrence of the same apparently de novo variants can be an indicator of mosaicism in either parent. Panel-based deep sequencing has the capacity to detect low-level mosaic variants with coverage exceeding the typical limit of detection provided by current, readily available sequencing techniques. In this study, we report three families with more than one affected offspring with either confirmed or apparent parental gonosomal or gonadal mosaicism for PIK3CD pathogenic variants. Data from targeted deep sequencing was suggestive of low-level maternal gonosomal mosaicism in Family 1. Through this approach we did not detect pathogenic variants in PIK3CD from parental samples in Family 2 and Family 3. We conclude that mosaicism was likely confined to the maternal gonads in Family 2. Subsequent long-read genome sequencing in Family 3 showed that the paternal chromosome harbored the pathogenic variant in PIK3CD in both affected children, consistent with paternal gonadal mosaicism. Detection of parental mosaic variants enables accurate risk assessment, informs reproductive decision-making, and provides helpful context to inform clinical management in families with PIK3CD pathogenic variants.

Background: An increasing number of research have applied neuroimaging techniques to explore the potential neurobiological mechanism of Cancer-related cognitive impairment (CRCI). Purpose: To explore the correlation between resting brain glucose metabolism and CRCI using 18F-FDG PET/CT in ovarian cancer (OC) patients. Methods: From December 2021 to March 2022, 38 patients with OC were selected as the study group, and 38 healthy women of the same age (±1 year) who underwent routine physical examination using PET/CT were selected as the control group. Patients received further assessment with the Montreal Cognitive Assessment Scale (MoCA) and Perceived Deficit Questionnaire (PDQ). Independent sample t-test and Spearman correlation were conducted for data analysis. Results: The resting brain glucose metabolism in the OC group was significantly lower than in the healthy controls. 60.52 % patients had neuropsychological impairment and retrospective memory were the most serious perceived cognitive impairments. The resting brain glucose metabolism in OC patients did not significantly correlate with neuropsychological performance but had significant positive correlation with subjective cognitive evaluation. Discussion: Resting glucose metabolism was low in OC patients and associated with subjective cognitive impairment but not objective neuropsychological test results. 18F-FDG PET/CT can be used to evaluate brain function in OC patients and provide reliable imaging indicators for early recognition of and intervention for changes in cognitive function.

Abstract The construction of bioartificial livers, such as liver organoids, offers significant promise for disease modeling, drug development, and regenerative medicine. However, existing methods for generating liver organoids have limitations, including lengthy and complex processes (taking 6–8 weeks or longer), safety concerns associated with pluripotency, limited functionality of pluripotent stem cell‐derived hepatocytes, and small, highly variable sizes (typically ≈50–500 µm in diameter). Prolonged culture also leads to the formation of necrotic cores, further restricting size and function. In this study, a straightforward and time‐efficient approach is developed for creating rapid self‐assembly mini‐livers (RSALs) within 12 h. Additionally, primary hepatocytes are significantly expanded in vitro for use as seeding cells. RSALs exhibit consistent larger sizes (5.5 mm in diameter), improved cell viability (99%), and enhanced liver functionality. Notably, RSALs are functionally vascularized within 2 weeks post‐transplantation into the mesentery of mice. These authentic hepatocyte‐based RSALs effectively protect mice from 90%‐hepatectomy‐induced liver failure, demonstrating the potential of bioartificial liver‐based therapy.

Background: Cardiovascular disease (CVD) is the leading cause of death worldwide, and statin therapy is the cornerstone of atherosclerotic cardiovascular disease. However, clinical practice is unsatisfactory, and there is significant interest in the risk of residual cardiovascular events. Traditional study methods make it difficult to exclude the crosstalk of confounding factors, and we investigated the impact of the ApoB/ApoA1 ratio on CVD using two-sample Mendelian randomization (MR) and multivariate Mendelian randomization (MVMR) methods. Methods: Two-sample MR and MVMR analyses were performed using pooled statistics from genome-wide association studies (GWAS) of ApoB/ApoA1 ratio (BAR), lipoprotein (a) (Lp(a)), and triglyceride (TG) in Europeans to assess the causal relationship between BAR, Lp(a), and TG with coronary artery disease (CAD). Results: The genetic prediction of BAR was significantly correlated with CAD (Inverse variance weighted (IVW) beta = 0.255; OR = 1.291; 95 % CI = 1.061–1.571; P = 0.011) in a two-sample MR analysis. MVMR studies showed that BAR (beta = 0.373; OR = 1.452; 95 % CI = 1.305–1.615; P = 7.217e-12), Lp (a) (beta = 0.238; OR = 1.269; 95 % CI = 1.216–1.323; P = 2.990e–28), and TG (beta = 0.155; OR = 1.168; 95 % CI = 1.074–1.270; P = 2.829e-04) were significantly associated with CAD. After further colinearity analyses of LASSO regressions, the results of multivariate analyses were similar for IVW, MR-Egger, MR-Lasso, and median methods. Conclusion: BAR is causally related to coronary artery disease. BAR is an independent predictor of CAD risk, independent of routine lipid measurements and other risk factors. TG and Lp(a) may be causally related to CAD, subject to verification in clinical practice.

Abstract Mitochondria are highly dynamic organelles capable of altering their sizes and shapes to maintain metabolic balance through coordinated fission and fusion processes. In various cancer types, mitochondrial hyperfragmentation has been frequently observed, contributing to the progression of cancer toward metastasis. Inverted formin 2 (INF2), which resides in the endoplasmic reticulum (ER), has been found to accelerate actin polymerization and drive mitochondrial fission. In this study, we demonstrate that INF2 expression is significantly upregulated in endometrial cancer (EC) and is associated with a poor prognosis in EC patients. INF2 promotes anchorage-dependent and independent EC cell growth in part by facilitating mitochondrial fission. Furthermore, in conditions of energy stress, AMP-activated protein kinase (AMPK) phosphorylates INF2 at Ser1077, leading to increased localization of INF2 to the ER and enhanced recruitment of the dynamin-related protein 1 (DRP1) to mitochondria. This AMPK-mediated phosphorylation of INF2 at Ser1077 facilitates mitochondrial division and promotes EC cell growth. Pathological examination using immunohistochemical analyses revealed a positive correlation between AMPK activity and phosphorylated INF2 (Ser1077) in EC specimens. Collectively, our findings uncover novel molecular mechanisms involving the AMPK-INF2 axis, which regulates mitochondrial dynamics and malignant cell growth in EC.

Abstract Background Germline heterozygous gain-of-function (GOF) mutations in the PIK3CD gene lead to a rare primary immunodeficiency disease known as activated phosphoinositide 3-kinase (PI3K) δ syndrome type 1(APDS1). Affected patients present a spectrum of clinical manifestations, particularly recurrent respiratory infections and lymphoproliferation, increased levels of serum immunoglobulin (Ig) M, Epstein-Barr virus (EBV) and cytomegalovirus (CMV) viremia. Due to highly heterogeneous phenotypes of APDS1, it is very likely that suspected cases may be misdiagnosed. Methods Herein we reported three patients with different clinical presentations but harboring pathogenic variants in PIK3CD gene detected by trio whole-exome sequencing (trio-WES) and confirmed by subsequent Sanger sequencing. Results Two heterozygous mutations (c.3061G > A, p.E1021K and c.1574 A > G, p.E525G) in PIK3CD (NM_005026.3) were identified by whole exome sequencing (WES) in the three patients. One of two patients with the mutation (c.3061G > A) presented with abdominal pain and diarrhea as the first symptoms, which was due to intussusception caused by multiple polyps of colon. The patient with mutation (c.1574 A > G) had an anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV)-like clinical manifestations, including multisystemic inflammation, acute nephritic syndrome, and positive perinuclear ANCA (p-ANCA), thus the diagnosis of ANCA-AAV was considered. Conclusions Our study expands the spectrums of clinical phenotype and genotype of APDS, and demonstrates that WES has a high molecular diagnostic yield for patients with immunodeficiency related symptoms, such as respiratory infections, multiple ecchymosis, ANCA-associated vasculitis, multiple ileocecal polyps, hepatosplenomegaly, and lymphoid hyperplasia. Trial registration Retrospectively registered.

Background: While radiation-induced lung injury decreases quality of life and suppresses efficacy of radiotherapy, to date, the relationship between radiation-induced lung injury and repair remains unclear. Our previous studies revealed that TNFRSF10B-RIPK1/RIPK3-MLKL signaling induces necroptosis of alveolar epithelial cells and potentiates radiation-induced lung injury. We also found that microRNA-541-3p is differentially expressed in radiation-damaged lungs. The connection between microRNA-541-3p, TNFRSF10B signaling, and TGFβ1 signaling is also unclear. Objective: This study was performed to explore the regulatory effects of microRNA-541-3p on TNFRSF10B and TGFβ1 signaling. Methods: Mouse alveolar epithelial cells were transfected with a vector expressing microRNA-541-3p to regulate expression of target genes. Flow cytometry, polymerase chain reaction, and western blotting were used to analyze cell necroptosis, target gene expression, and target protein expression, respectively. Results: Overexpression of microRNA-541-3p positively regulated TNFRSF10B-RIPK1/RIPK3-MLKL signaling through Rac2 to induce cell necroptosis. MicroRNA-541-3p negatively regulates Rac2. MicroRNA-541-3p and Rac2 regulate the expression of Tgf-beta1 and its encoded proteins. Conclusions: The Rac2 gene synchronously regulates TNFRSF10B-RIPK1/RIPK3-MLKL and TGFβ1 signaling. MicroRNA-541-3P/Rac2 act as mediators of radiation damage and repair signaling.

Abstract Background The aim of this study was to find early predictors of Intravenous Immunoglobulin (IVIG)-Resistant Kawasaki Disease. Methods Patients diagnosed with Kawasaki disease were enrolled in this study. Univariate analysis and multiple logistic regression were used to analyze the clinical characteristics and laboratory findings of patients in both groups before IVIG treatment. Independent predictors of Intravenous Immunoglobulin-Resistant Kawasaki Disease were analyzed, and a prediction model for children with Intravenous Immunoglobulin-Resistant Kawasaki Disease was constructed. Results A total of 108 children (67 males and 41 females) with IVIG-sensitive Kawasaki disease and 31 children (20 males and 11 females) with IVIG-resistant Kawasaki disease participated in this study. Compared with the IVIG-sensitive group, the duration of hospitalization, ALT, AST, GLB, r-GT, IgG, PCT, and ESR was elevated in the IVIG-resistant KD group, and ATG16L1, LC3II, BECN1, RBC, HGB, ALB, A/G, and CK were significantly lower (P

The topography of mountainous areas is characterized by large undulations, which lead to a very complex wind field at bridge sites in mountain valleys. The influence of oncoming wind speed on long-span bridges built in mountain valleys is quite pronounced. To investigate the wind characteristics at a bridge site in a mountain valley under different oncoming wind speeds, a wind tunnel test of a terrain model with a scaling ratio of 1:1000, where a long-span bridge would be built in the V-shaped canyon, was conducted. Uniform and atmospheric boundary layer (ABL) inflows were both applied, and the effect of different oncoming wind speeds (basic wind speeds of 6 m/s, 8 m/s, 10 m/s, 12 m/s, and 14 m/s) under three wind directions (0°, 30°, and 180°) on the wind characteristics at the main beam and two bridge towers were studied. The results indicate that increasing oncoming wind speed leads to decreased wind profiles and wind speed amplification factors and increased wind attack angles, while wind yaw angles remain largely unchanged. In addition, compared to ABL inflow, the variation of fluctuating wind characteristics is more pronounced with the oncoming wind speed under uniform inflow. Under uniform inflow conditions, increasing the oncoming wind speed causes decreased turbulence intensity, reduces the peak frequency of the power spectrum, and slows down the high-frequency decay rate. Under ABL inflow conditions, turbulence intensity and the power spectrum remain unchanged with different oncoming wind speeds. Additionally, the turbulent integral scale derived from fitting with the von Kármán wind spectrum is sufficiently accurate, and the variation in the turbulent integral scale is greatly influenced by the terrain. Furthermore, higher wind speeds result in stronger coherence between two points. When two points are at different locations but with the same spacing, the coherence function remains roughly the same. Locations with higher kurtosis and skewness values exhibit steeper probability density functions, with larger kurtosis and skewness coefficients typically found on the leeward side. High wind speeds are more detrimental to bridge safety, and appropriate preventive measures should be implemented in advance to address extreme conditions that may arise at high wind speeds.

Remote sensing image (RSI) scene classification aims to identify semantic categories in RSI using neural networks. However, high-performance deep neural networks typically demand substantial storage and computational resources, making practical deployment challenging. Knowledge distillation has emerged as an effective technique for developing compact models that maintain high classification accuracy in RSI tasks. Existing knowledge distillation methods often overlook the high inter-class similarity in RSI scenes, leading to low-confidence soft labels from the teacher model, which can mislead the student model. Conversely, overly confident soft labels may discard valuable non-target information. Additionally, the significant intra-class variability in RSI contributes to instability in the model’s decision boundaries. To address these challenges, we propose an efficient method called instance-level scaling and dynamic margin-alignment knowledge distillation (ISDM) for RSI scene classification. To balance the target and non-target class influence, we apply an entropy regularization loss to scale the teacher model’s target class at the instance level. Moreover, we introduce dynamic margin alignment between the student and teacher models to improve the student’s discriminative capability. By optimizing soft labels and enhancing the student’s ability to distinguish between classes, our method reduces the effects of inter-class similarity and intra-class variability. Experimental results on three public RSI scene classification datasets (AID, UCMerced, and NWPU-RESISC) demonstrate that our method achieves state-of-the-art performance across all teacher–student pairs with lower computational costs. Additionally, we validate the generalization of our approach on general datasets, including CIFAR-100 and ImageNet-1k.

The Tian Shan is a typical active intracontinental orogenic belt that is driven by the ongoing indentation of India into Eurasia. However, the geological features of Quaternary deformation, especially in the easternmost sector near Harlik Mountain, remain elusive. Field observations, topographic analysis, and Electron Spin Resonance (ESR) dating were employed to comprehensively assess the deformation features and evaluate the deformation pattern for this region during the Quaternary period. The results disclose evidence of deformation in the northern and southern foreland basins of Harlik Mountain. In the Barkol Basin to the north, crustal shortening results in the formation of surface scarps and folds, indicating north-directed thrusting, with a shortening rate of ~0.15 mm/yr. In the Hami Basin, the north-directed thrust elevates the granites, which offset the alluvial fans, with a shortening rate of ~0.18 mm/yr. Together with the shortening along the boundary fault, the aggregated north–south shortening rate is approximately 0.69 mm/yr in the easternmost Tian Shan, corresponding with the differential motion rate between the north and south Harlik Mountain revealed by the GPS velocity. These findings imply that, distal to the collision zone, tectonic strain in the eastern Tian Shan is primarily accommodated through the reactivation of pre-existing strike–slip faults, with crustal shortening concentrated at the overlapping position of parallel northeast-trending left-lateral strike–slip faults.

Multi-object tracking tasks aim to assign unique trajectory codes to targets in video frames. Most detection-based tracking methods use Kalman filtering algorithms for trajectory prediction, directly utilizing associated target features for trajectory updates. However, this approach often fails, with camera jitter and transient target loss in real-world scenarios. This paper rethinks state prediction and fusion based on target temporal features to address these issues and proposes the SimpleTrackV2 algorithm, building on the previously designed SimpleTrack. Firstly, to address the poor prediction performance of linear motion models in complex scenes, we designed a target state prediction algorithm called LSTM-MP, based on long short-term memory (LSTM). This algorithm encodes the target’s historical motion information using LSTM and decodes it with a multilayer perceptron (MLP) to achieve target state prediction. Secondly, to mitigate the effect of occlusion on target state saliency, we designed a spatiotemporal attention-based target appearance feature fusion (TSA-FF) target state fusion algorithm based on the attention mechanism. TSA-FF calculates adaptive fusion coefficients to enhance target state fusion, thereby improving the accuracy of subsequent data association. To demonstrate the effectiveness of the proposed method, we compared SimpleTrackV2 with the baseline model SimpleTrack on the MOT17 dataset. We also conducted ablation experiments on TSA-FF and LSTM-MP for SimpleTrackV2, exploring the optimal number of fusion frames and the impact of different loss functions on model performance. The experimental results show that SimpleTrackV2 handles camera jitter and target occlusion better, achieving improvements of 1.6%, 3.2%, and 6.1% in MOTA, IDF1, and HOTA, respectively, compared to the SimpleTrack algorithm.

Myocardial infarction (MI), a severe outcome of cardiovascular disease, poses a serious threat to human health. Uncontrolled inflammation and excessive cardiomyocyte death, following an infarction event, significantly contribute to both the mortality rate and complications associated with MI. The protein IL-4-induced gene 1 (IL4I1 or FIG1) serves as a natural inhibitor of innate and adaptive immunity, playing a crucial role in CD4+ T cell differentiation, macrophage polarization, and ferroptosis inhibition. Previous studies have linked IL4I1 to acute MI. This review summarizes evidence from both basic and clinical research, highlighting IL4I1 as a critical immunoregulatory enzyme that not only regulates inflammatory responses, but also potentially mitigates MI-induced damage.

Abstract Background Germinal matrix hemorrhage (GMH) is a devastating neonatal stroke, in which neuroinflammation is a critical pathological contributor. Slit2, a secreted extracellular matrix protein, plays a repulsive role in axon guidance and leukocyte chemotaxis via the roundabout1 (Robo1) receptor. This study aimed to explore effects of recombinant Slit2 on neuroinflammation and the underlying mechanism in a rat model of GMH. Methods GMH was induced by stereotactically infusing 0.3 U of bacterial collagenase into the germinal matrix of 7-day-old Sprague Dawley rats. Recombinant Slit2 or its vehicle was administered intranasally at 1 h after GMH and daily for 3 consecutive days. A decoy receptor recombinant Robo1 was co-administered with recombinant Slit2 after GMH. Slit2 siRNA, srGAP1 siRNA or the scrambled sequences were administered intracerebroventricularly 24 h before GMH. Neurobehavior, brain water content, Western blotting, immunofluorescence staining and Cdc42 activity assays were performed. Results The endogenous brain Slit2 and Robo1 expressions were increased after GMH. Robo1 was expressed on neuron, astrocytes and infiltrated peripheral immune cells in the brain. Endogenous Slit2 knockdown by Slit2 siRNA exacerbated brain edema and neurological deficits following GMH. Recombinant Slit2 (rSlit2) reduced neurological deficits, proinflammatory cytokines, intercellular adhesion molecules, peripheral immune cell markers, neuronal apoptosis and Cdc42 activity in the brain tissue after GMH. The anti-neuroinflammation effects were reversed by recombinant Robo1 co-administration or srGAP1 siRNA. Conclusions Recombinant Slit2 reduced neuroinflammation and neuron apoptosis after GMH. Its anti-neuroinflammation effects by suppressing onCdc42-mediated brain peripheral immune cells infiltration was at least in part via Robo1–srGAP1 pathway. These results imply that recombinant Slit2 may have potentials as a therapeutic option for neonatal brain injuries.

ObjectiveTo explore the association of work-family conflict with suicidal ideation among medical staff for developing relevant interventions to prevent suicidal ideation and behavior in the population. MethodsA face-to-face questionnaire survey was conducted among 3 426 medical staff recruited at 12 general hospitals in 12 districts/counties of Shandong province from November 2018 through January 2019. The participants were asked to answer questions on lifetime and past one year suicidal ideation and scales including Center for Epidemiological Studies Depression (CES-D), Perceived Social Support Scale (PSSS)，Simplified Coping Style Questionnaire (SCSQ)，and the Work-Family Conflict Scale developed by domestic researchers. Results Of all the participants, 9.1% and 7.0% reported lifetime and one-year suicidal ideation. Multivariate logistic regression analysis revealed following risk factors for lifetime and one-year suicidal ideation: higher education (doctor vs. below undergraduate: odds ratio [OR] = 4.32, P < 0.001 and OR = 4.21, P < 0.01), suffering physical illness (OR = 1.58, P < 0.01 and OR = 1.51, P < 0.05), with work-family conflict (OR = 1.03, P < 0.01 and OR = 1.02, P < 0.05), and having depressive symptoms (OR = 1.09 and OR = 1.10, both P < 0.001); while, male gender was a protective factors against lifetime and one-year suicidal ideation (OR = 0.54 and OR = 0.46, both P < 0.001). Mediation effect analysis demonstrated that depressive symptoms has a mediating effect on the correlation between work-family conflict and lifetime and one-year suicidal ideation, with the effect values of 0.0237 and 0.0265, accounting for 45.84% and 53.64% of the total effect, respectively. Conclusion Among medical stuff, work-family conflict exerts a direct impact on suicidal ideation and depressive symptoms mediate the promotion effect of work-family conflict on suicidal ideation.

Abstract Background Neuro-Behçet's disease (NBD), characterized by isolated intracranial hypertension, is a rarely encountered condition, especially in children. In this study, we describe the treatment of a pediatric patient with NBD, who exhibited isolated intracranial pressure elevation as indicated by the initial manifestation of diplopia and physical examination finding of papilledema. Case presentation An 8-year-old boy was admitted to the hospital with a confirmed diagnosis of Behçet's disease (BD) over eight months. The patient also presented with the symptom of diplopia for three days. The evaluation of the patient’s nervous system did not reveal any apparent abnormalities. The measurement of cerebrospinal fluid pressure yielded a reading of 470 mm H2O. The examination of the fundus indicated papilledema, and imaging scans revealed evidence of focal demyelination. The symptoms of the child showed alleviation after the administration of mannitol, methylprednisolone, and azathioprine. Furthermore, this study involved a comprehensive analysis of 18 cases of NBD with isolated intracranial hypertension, comprising one case reported herein and 17 cases from the literature review. Three cases were children, and an equal distribution of males and females 9:9 was noted. The average age at the onset of symptoms was 24.7 years (8-38 years). Headache (90%) was the most commonly reported clinical manifestation, followed by blurred vision or diplopia (80%). The ocular manifestations included papilledema (100%), abducent nerve paralysis (20%) and local eye hemorrhages in the retina (30%). Notably, 88.9% of these ocular manifestations were relieved or cured after treatment. Conclusion This study presents the first reported case of NBD with isolated intracranial hypertension in the pediatric population of China. In a child with Bechet's disease presenting with features of raised intracranial pressure, it is important to be aware of neuro Bechet's presenting with intracranial hypertension without other neurological abnormalities. This will help make early diagnosis, institute treatment and prevent sequelae resulting from untreated raised intracranial pressure.

Abstract Cellular senescence serves as a fundamental and underlying activity that drives the aging process, and it is intricately associated with numerous age-related diseases, including Alzheimer's disease (AD), a neurodegenerative aging-related disorder characterized by progressive cognitive impairment. Although increasing evidence suggests that senescent microglia play a role in the pathogenesis of AD, their exact role remains unclear. In this study, we quantified the levels of lactic acid in senescent microglia, and hippocampus tissues of naturally aged mice and AD mice models (FAD4T and APP/PS1). We found lactic acid levels were significantly elevated in these cells and tissues compared to their corresponding counterparts, which increased the level of pan histone lysine lactylation (Kla). We aslo identified all histone Kla sites in senescent microglia, and found that both the H3K18 lactylation (H3K18la) and Pan-Kla were significantly up-regulated in senescent microglia and hippocampus tissues of naturally aged mice and AD modeling mice. We demonstrated that enhanced H3K18la directly stimulates the NFκB signaling pathway by increasing binding to the promoter of Rela (p65) and NFκB1(p50), thereby upregulating senescence-associated secretory phenotype (SASP) components IL-6 and IL-8. Our study provides novel insights into the physiological function of Kla and the epigenetic regulatory mechanism that regulates brain aging and AD. Specifically, we have identified the H3K18la/NFκB axis as a critical player in this process by modulating IL-6 and IL-8. Targeting this axis may be a potential therapeutic strategy for delaying aging and AD by blunting SASP.