Catalase catalyzed tannic acid-Fe3+ network coating: A theranostic strategy for intestinal barrier restoration.

Epithelial barrier impairment of intestinal inflammation leads to the leakage of bacteria, antigens and consequent persistent immune imbalance. Restoring the barrier function holds promise for management of intestinal inflammation, while the theragnostic strategies are limited. In this study, we developed a novel coating by catalase (CAT)-catalyzed polymerization of tannic acid (TA) and combined chelation network with Fe3+. TA-Fe3+ coating was self-polymerized in situ along the small intestinal mucosa, demonstrating persistent adhesion properties and protective function. In enteritis models, sequential administration of TA-Fe3+ complex solution effectively restored the barrier function and alleviated the intestinal inflammation. Overexpressed CAT in inflammatory lesion is more favorable for the in situ targeting growth of TA-Fe3+ coating onto the defective barrier. Based on the high longitudinal relaxivity of Fe3+, the pathologically catalyzed coating facilitated the visualization of intestinal barrier impairment through MRI. In conclusion, the novel TA-Fe3+ delivery coating proposed an alternative approach to promote theranostic intervention for intestinal diseases.

Nurturing gut health: role of m6A RNA methylation in upholding the intestinal barrier.

The intestinal lumen acts as a critical interface connecting the external environment with the body's internal state. It's essential to prevent the passage of harmful antigens and bacteria while facilitating nutrient and water absorption. The intestinal barriers encompass microbial, mechanical, immunological, and chemical elements, working together to maintain intestinal balance. Numerous studies have associated m6A modification with intestinal homeostasis. This review comprehensively outlines potential mechanisms through which m6A modification could initiate, exacerbate, or sustain barrier damage from an intestinal perspective. The pivotal role of m6A modification in preserving intestinal equilibrium provides new insights, guiding the exploration of m6A modification as a target for optimizing preventive and therapeutic strategies for intestinal homeostasis.

p20BAP31 promotes cell apoptosis via interaction with GRP78 and activating the PERK pathway in colorectal cancer.

Colorectal cancer (CRC) is the second most deadly cancer worldwide. Although various treatments for CRC have made progress, they have limitations. Therefore, the search for new effective molecular targets is important for the treatment of CRC. p20BAP31 induces apoptosis through diverse pathways and exhibits greater sensitivity in CRC. Therefore, a comprehensive exploration of the molecular functions of p20BAP31 is important for its application in anti-tumor therapy. In this study, we showed that exogenous p20BAP31 was still located in the ER and significantly activated the unfolded protein response (UPR) through the PERK pathway. The activation of the PERK pathway is prominent in p20BAP31-induced reactive oxygen species (ROS) accumulation and apoptosis. We found, for the first time, that p20BAP31 leads to ER stress and markedly attenuates tumor cell growth in vivo. Importantly, mechanistic investigations indicated that p20BAP31 competitively binds to GRP78 from PERK and causes hyperactivation of the UPR. Furthermore, p20BAP31 upregulates the expression of GRP78 by promoting HSF1 nuclear translocation and enhancing its binding to the GRP78 promoter. These findings reveal p20BAP31 as a regulator of ER stress and a potential target for tumor therapy, and elucidate the underlying mechanism by which p20BAP31 mediates signal transduction between ER and mitochondria.

p20BAP31 Induces Autophagy in Colorectal Cancer Cells by Promoting PERK-Mediated ER Stress.

B-cell receptor-associated protein 31 (BAP31) is an endoplasmic reticulum (ER) membrane protein involved in apoptosis and autophagy by communication with ER and mitochondria. BAP31 is cleaved by caspase-8 and generates a proapoptotic fragment, p20BAP31, which has shown to induce ER stress and apoptosis through multiple pathways. In this study, we found that p20BAP31 significantly increased the agglomeration of LC3 puncta, suggesting the occurrence of autophagy. Therefore, it is meaningful to explore the mechanism of p20BAP31-induced autophagy, and further analyze the relationships among p20BAP31-induced autophagy, ER stress and apoptosis. The data showed that p20BAP31 induced autophagy by inhibition of the PI3K/AKT/mTOR signaling in colorectal cells. ER stress inhibitor 4-PBA and PERK siRNA alleviated p20BAP31-induced autophagy; in turn, autophagy inhibitors 3-MA and CQ did not affect p20BAP31-induced ER stress, suggesting that p20BAP31-induced ER stress is the upstream of autophagy. We also discovered that ROS inhibitor NAC inhibited p20BAP31-induced autophagy. Furthermore, inhibition of autophagy by CQ suppressed p20BAP31-induced apoptosis and ameliorated cell proliferation. Importantly, p20BAP31 markedly reduced the tumor size in vivo, and significantly enhanced the autophagy levels in the tumor tissues. Collectively, p20BAP31 initiates autophagy by inhibiting the PI3K/AKT/mTOR signaling and activating the PERK-mediated ROS accumulation, further promotes p20BAP31-induced apoptosis and ultimately results in cell death. This study comprehensively reveals the potential mechanism of p20BAP31-induced cell death, which may provide new strategies for antitumor therapy.

Effect of Acupuncture on Tear Proteomics in Patients with Video Display Terminal-Related Dry Eye.

Acupuncture is widely used to treat dry eye disease (DED), but its effect has not been reported in treating video display terminal (VDT)-related dry eye, and the mechanism of acupuncture on VDT-related dry eye is also unknown. In our study, the tear proteome was compared with identifying possible mechanisms and biomarkers for predicting acupuncture effectiveness in VDT-related dry eye. The results showed that the ocular surface disease index scores were significantly different between the acupuncture group (AC group) and artificial tears group (AT group) at the end of the study, whereas tear film breakup time (TFBUT) and Schirmer I test (SIT) were not significantly different between the groups. Proteome changes pre- and post-treatment in the AC group were associated with B cell-related immune processes, inflammation, glycolysis, and actin cytoskeleton. Furthermore, the proteins hexosaminidase A and mannose-binding lectin 1 could prospectively predict whether acupuncture treatment was effective. Therefore, we believe that acupuncture can provide greater improvement in the clinical symptoms of VDT-related dry eye than artificial tears. The mechanism of acupuncture in VDT-related dry eye treatment may be associated with glycolysis- and actin cytoskeleton remodeling-mediated inflammatory and immune processes. Additionally, hexosaminidase A and mannose-binding lectin 1 are biomarkers for predicting the efficacy of acupuncture for VDT-related dry eye.

Minimally invasive management of persistent retroperitoneal infections following ERCP duodenal perforations.

Duodenal perforation is the most serious complication of endoscopic retrograde cholangiopancreatography (ERCP), with an incidence of 0.09-1.67% but a high mortality rate of 8-23%. The Stapfer classification categorizes ERCP perforations into four types based on location: I) lateral/medial duodenal wall, II) perivaterian, III) distal bile duct related to instrumentation, IV) retroperitoneal air alone. While surgery is recommended for diagnosed perforations due to the mortality risk, there is no established treatment for resulting long-term retroperitoneal infections. We describe our experience managing such cases.

Genome assembly of autotetraploid Actinidia arguta highlights adaptive evolution and enables dissection of important economic traits.

Actinidia arguta, the most widely distributed Actinidia species and the second cultivated species in the genus, can be distinguished from the currently cultivated Actinidia chinensis on the basis of its small and smooth fruit, rapid softening, and excellent cold tolerance. Adaptive evolution of tetraploid Actinidia species and the genetic basis of their important agronomic traits are still unclear. Here, we generated a chromosome-scale genome assembly of an autotetraploid male A. arguta accession. The genome assembly was 2.77 Gb in length with a contig N50 of 9.97 Mb and was anchored onto 116 pseudo-chromosomes. Resequencing and clustering of 101 geographically representative accessions showed that they could be divided into two geographic groups, Southern and Northern, which first diverged 12.9 million years ago. A. arguta underwent two prominent expansions and one demographic bottleneck from the mid-Pleistocene climate transition to the late Pleistocene. Population genomics studies using paleoclimate data enabled us to discern the evolution of the species' adaptation to different historical environments. Three genes (AaCEL1, AaPME1, and AaDOF1) related to flesh softening were identified by multi-omics analysis, and their ability to accelerate flesh softening was verified through transient expression assays. A set of genes that characteristically regulate sexual dimorphism located on the sex chromosome (Chr3) or autosomal chromosomes showed biased expression during stamen or carpel development. This chromosome-level assembly of the autotetraploid A. arguta genome and the genes related to important agronomic traits will facilitate future functional genomics research and improvement of A. arguta.

Penicillium oxalicum SL2-enhanced nanoscale zero-valent iron effectively reduces Cr(VI) and shifts soil microbiota.

Most current researches focus solely on reducing soil chromium availability. It is difficult to reduce soil Cr(VI) concentration below 5.0 mg kg-1 using single remediation technology. This study introduced a sustainable soil Cr(VI) reduction and stabilization system, Penicillium oxalicum SL2-nanoscale zero-valent iron (nZVI), and investigated its effect on Cr(VI) reduction efficiency and microbial ecology. Results showed that P. oxalicum SL2-nZVI effectively reduced soil total Cr(VI) concentration from 187.1 to 3.4 mg kg-1 within 180 d, and remained relatively stable at 360 d. The growth curve of P. oxalicum SL2 and microbial community results indicated that γ-ray irradiation shortened the adaptation time of P. oxalicum SL2 and facilitated its colonization in soil. P. oxalicum SL2 colonization activated nZVI and its derivatives, and increased soil iron bioavailability. After restoration, the negative effect of Cr(VI) on soil microorganisms was markedly alleviated. Cr(VI), Fe(II), bioavailable Cr/Fe, Eh, EC and urease (SUE) were the key environmental factors of soil microbiota. Notably, Penicillium significantly stimulated the growth of urease-positive bacteria, Arthrobacter, Pseudarthrobacter, and Microvirga, synergistically reducing soil chromium availability. The combination of P. oxalicum SL2 and nZVI is expected to form a green, economical and long-lasting Cr(VI) reduction stabilization strategy.

The colonization of Penicillium oxalicum SL2 on rice root surface increased Pb interception capacity of iron plaque and decreased Pb uptake by roots.

The exploration of microbial resources to reduce Pb accumulation in rice attracted great attention. In this study, we found Penicillium oxalicum SL2, a Pb-tolerant strain with good capability of dissolving phosphorus and stabilizing Pb in soil, was able to colonize on the root surface of rice seedlings without additional carbon sources, and promoted the secretion of metabolites related to amino acid metabolism, organic acid metabolism, signal transduction and other pathways in rhizosphere exudates, in which the secretion of oxalate increased by 47.7 %. However, P. oxalicum SL2 increased Fe(II) proportion and Fe availability on the root surface, resulting in iron plaque content decrease. Moreover, by converting root surface Pb from Pb-Fe state to PbC2O4 and Pb-P compounds, P. oxalicum SL2 increased Pb intercept capacity of iron plaque by 118.0 %. Furthermore, P. oxalicum SL2 regulated element distribution on the root surface, and reduced the relative content of Pb on the maturation zone of root tip, which was conducive to reducing Pb uptake by apoplastic pathway and the risk of Pb accumulation in root system. Our findings further revealed the interaction between P. oxalicum SL2 and rice root, providing a theoretical basis for the development and application of microbial agents in Pb-contaminated farmland.

MOCAT: multi-omics integration with auxiliary classifiers enhanced autoencoder.

BACKGROUND: Integrating multi-omics data is emerging as a critical approach in enhancing our understanding of complex diseases. Innovative computational methods capable of managing high-dimensional and heterogeneous datasets are required to unlock the full potential of such rich and diverse data. METHODS: We propose a Multi-Omics integration framework with auxiliary Classifiers-enhanced AuToencoders (MOCAT) to utilize intra- and inter-omics information comprehensively. Additionally, attention mechanisms with confidence learning are incorporated for enhanced feature representation and trustworthy prediction. RESULTS: Extensive experiments were conducted on four benchmark datasets to evaluate the effectiveness of our proposed model, including BRCA, ROSMAP, LGG, and KIPAN. Our model significantly improved most evaluation measurements and consistently surpassed the state-of-the-art methods. Ablation studies showed that the auxiliary classifiers significantly boosted classification accuracy in the ROSMAP and LGG datasets. Moreover, the attention mechanisms and confidence evaluation block contributed to improvements in the predictive accuracy and generalizability of our model. CONCLUSIONS: The proposed framework exhibits superior performance in disease classification and biomarker discovery, establishing itself as a robust and versatile tool for analyzing multi-layer biological data. This study highlights the significance of elaborated designed deep learning methodologies in dissecting complex disease phenotypes and improving the accuracy of disease predictions.

Effectiveness of dyadic interventions among cancer dyads: An overview of systematic reviews and meta-analyses.

AIMS AND OBJECTIVE: To summarize evidence from systematic reviews (SRs)/meta-analyses (MAs) regarding the impact of dyadic interventions delivered to both members of a cancer dyad, including a cancer patient and caregiver (e.g. family caregiver, intimate partner). DESIGN: This overview of SRs was conducted in accordance with the preferred reporting items for overviews of reviews statement. METHODS: A comprehensive search of multiple databases, including PubMed, Cochrane Library, Embase, CINAHL, Web of Science, China National Knowledge Infrastructure and Wan Fang. The methodological and reporting quality of SRs and MAs was assessed using the Assessing the Methodological Quality of Systematic Reviews 2. The quality of the included SRs/MAs was evaluated using the Grades of Recommendations, Assessment, Development and Evaluation approach. RESULTS: Eighteen SRs/MAs undertook quantitative synthesis to assess the impact of dyadic interventions on cancer dyads. Both the credibility of the SRs/MAs and the evidence quality of the outcome measures were below satisfactory standards. Prior SRs/MAs revealed several limitations such as lack of pre-published protocols or research objectives, failure to report excluded studies and insufficient details on funding sources for individual studies. CONCLUSIONS: Dyadic interventions may prove advantageous for the physical health and dyadic adjustment of cancer dyads. Nevertheless, the reported results of dyadic interventions on the psychological health of patient-caregiver dyads affected by cancer are inconsistent. Thus, rigorous and comprehensive studies are requisite to establish reliable evidence for conclusive determinations. RELEVANCE TO CLINICAL PRACTICE: The findings of this overview can guide healthcare practitioners when considering the use of dyadic interventions for cancer dyads. Moreover, these findings have the potential to enhance the integration of these approaches into clinical practice. PATIENT OR PUBLIC CONTRIBUTION: Our paper presents an overview of systematic reviews, and therefore, such specific details may not be relevant to our study.

Dual Regulatory Role of Penicillium oxalicum SL2 in Soil: Phosphorus Solubilization and Pb Stabilization.

The mechanisms of the P. oxalicum SL2-mediated microbial community on phosphorus solubilization and Pb stabilization were investigated through a 90-day soil experiment. In the treatments inoculated with P. oxalicum SL2, the amount of P. oxalicum SL2-GFP remained at 77.8%-138.6% of the initial inoculation amount after 90 days, and the available phosphorus (AP) content increased 21.7%-40.8% while EDTA-Pb decreased 29.9%-43.2% compared with CK treatment. SEM-EDS results showed that P. oxalicum SL2 changed the agglomeration degree of microaggregates and promoted the combination of Pb with C and O elements. These phenomena were enhanced when applied with Ca3(PO4)2. Microbial community analysis showed that P. oxalicum SL2 improved soil microbial activity, in which the fungi absolute abundance increased about 15 times within 90 days. Correlation analyses and a partial least-squares path model showed that the activation of Penicillium, Ascobolus, Humicola, and Spizellomyces in a fungal community increased the content of oxalate and AP, which directly decreased EDTA-Pb content, while the change of Bacillus, Ramlibacter, Gemmatimonas, and Candidatus Solibacter in the bacterial community regulated Fe/Mn/S/N cycle-related functions, thus promoting the conversion of Pb to oxidizable state. Our findings highlight that P. oxalicum SL2 enhanced the microbial-induced phosphate precipitation process by activating soil microbial communities and regulating their ecological functions.

More effective than direct contact: Nano hydroxyapatite pre-treatment regulates the growth and Cd uptake of rice (Oryza sativa L.) seedlings.

Cd contamination in rice urgently needs to be addressed. Nano hydroxyapatite (n-HAP) is an eco-friendly material with excellent Cd fixation ability. However, due to its own high reactivity, innovative application of n-HAP in the treatment of Cd contamination in rice is needed. In this study, we proposed a new application, namely n-HAP pre-treatment, which can effectively reduce Cd accumulation in rice and alleviate Cd stress. The results showed that 80 mg/L n-HAP pre-treatment significantly reduced Cd content in rice shoot by 35.1%. Biochemical and combined transcriptomic-proteomic analysis revealed the possible molecular mechanisms by which n-HAP pre-treatment promoted rice growth and reduced Cd accumulation. (1) n-HAP pre-treatment regulated gibberellin and jasmonic acid synthesis-related pathways, increased gibberellin content and decreased jasmonic acid content in rice root, which promoted rice growth; (2) n-HAP pre-treatment up-regulated gene CATA1 expression and down-regulated gene OsGpx1 expression, which increased rice CAT activity and GSH content; (3) n-HAP pre-treatment up-regulated gene OsZIP1 expression and down-regulated gene OsNramp1 expression, which reduced Cd uptake, increased Cd efflux from rice root cells.

Corrigendum: Unveiling the key genes, environmental toxins, and drug exposures in modulating the severity of ulcerative colitis: a comprehensive analysis.

[This corrects the article DOI: 10.3389/fimmu.2023.1162458.].

Snare traction-assisted method during endoscopic resection for gastric submucosal tumors: a single center case series.

BACKGROUND: Endoscopic resection (ER) of gastric submucosal tumors (G-SMTs) is challenging due to the difficulty of exposure. Traction-assisted ER has been shown to provide better outcomes than traditional endoscopic operation by exposing the dissection plane. In this study, we investigated the efficacy and safety of the snare traction-assisted method in ER of G-SMTs. METHOD: From May 2021 to March 2023, we used snare traction-assisted method to treat 24 patients with 24 G-SMTs in our department. Clinical characteristics and the outcomes of ER were recorded. RESULT: The mean tumor diameter was 1.8±0.9 cm. Six G-SMTs underwent endoscopic submucosal dissection (ESD), and 18 underwent endoscopic full-thickness resection (EFTR). En bloc resection and R0 resection was achieved in all the 24 lesions. The average procedure time was 45.4 ± 23.4 minutes. The patients were discharged in 5.0 days after procedures, without delayed bleeding or other adverse events. CONCLUSION: Snare traction-assisted method provides an effective traction for endoscopic resection of G-SMTs even if the tumor is difficult to remove. While further studies comparing the snare traction-assisted method with the conventional procedure are necessary.

Breaking boundaries: laparoscopic and endoscopic collaboration in appendectomy.

Background The combination of endoscopy and laparoscopic assistance is gaining attention due to its minimally invasive approach and the potential to improve the safety of surgical treatment for potential malignant tumors at the base of the appendix. Methods Initially, we attempted an endoscopic resection for a patient with a large adenoma in the ileocecal region, with involvement of the appendiceal orifice. However, due to intraabdominal adhesions, a smooth resection was not possible. Therefore, in collaboration with the surgical team, we proceeded with the laparoscopic release of adhesions followed by endoscopic appendectomy. The surgical site was closed using endoscopic purse-string sutures, and intestinal and intraperitoneal dual drainage tubes were placed. Results The patient had a favorable recovery following the appendectomy, with no adverse complications. One year later, the follow-up endoscopy revealed excellent closure of the surgical site. Conclusions The integration of internal medicine and surgery has become an inevitable trend in the advancement of medical disciplines. The laparoscopic and endoscopic combined surgery enhances the cooperation between internal medicine and surgery, ultimately benefiting the patients. This significant attempt holds the promise of further supplementation and support from additional clinical data.

Clinical Efficacy of 2-Needle Joint Lavage for Osteoarthritis-Related Knee Pain and Predictors of Response Based on Knee MRI Osteoarthritis Knee Score: A Medical Records Review Study.

BACKGROUND: Knee osteoarthritis (OA) is notoriously difficult to treat. Pain is the key symptom for patients to seek medical attention. This study aimed to evaluate the therapeutic efficacy of joint lavage (JL) for OA-related knee pain and to explore the knee pathological changes detected by magnetic resonance imaging that may affect the prognosis of patients who received JL. METHODS: Eighty-two hospitalized patients who were diagnosed with knee OA and received JL in our department were finally enrolled in this study. The patients' clinical data including Numeric Rating Scale (NRS), Western Ontario and McMaster Osteoarthritis Index pain subscale, analgesic medication usage, adverse events, and magnetic resonance imaging data of the affected knee joint scored by the MRI Osteoarthritis Knee Score were recorded and analyzed. RESULTS: The NRS scores significantly decreased after JL and remained steady until 6 months ( p < 0.001). The Western Ontario and McMaster Osteoarthritis Index pain scores and the percentage of patients who needed analgesic medication significantly decreased at 6 months compared with baseline ( p < 0.001). At 6 months after JL, 51 of the 82 patients experienced ≥50% improvement in their NRS scores (effective). Multivariate binary logistic regression analysis revealed that duration of pain (odds ratio [OR], 1.022; 95% confidence interval [CI], 1.003-1.042; p = 0.024), bone marrow lesion score (OR, 1.221; 95% CI, 1.028-1.450; p = 0.023), and cartilage loss score (OR, 1.272; 95% CI, 1.021-1.585; p = 0.032) significantly influenced the therapeutic efficacy of JL. CONCLUSIONS: JL treatment can significantly alleviate the OA-related knee pain in at least 6 months. JL tends to provide limited benefit for patients with long duration of pain, serious bone marrow lesions, and severe cartilage loss.

Altered gut microbiota and metabolites in untreated myasthenia gravis patients.

Objective: The homeostasis of the immune system is influenced by the gut microbiota. Previous studies have reported dysbiosis in the gut microbiota of myasthenia gravis (MG) patients. To investigate potential alterations in gut microbiota and metabolites in newly diagnosed and untreated MG patients, we conducted a case-control study. Methods: Fecal samples were collected from 11 newly diagnosed and untreated MG patients as well as 11 age-and sex-matched healthy controls. These samples underwent analysis for gut microbiota using 16S ribosomal RNA (rRNA) gene sequencing, while fecal metabolome was analyzed using liquid chromatography-electrospray tandem mass spectrometry system (LC-ESI-MS/MS). Results: The microbial community richness (observed species) and diversity (Shannon and Simpson indices) were significantly lower in the MG group compared to the control group. Microbiota composition analysis revealed significant differences between the MG and control groups at phylum, family, and genus levels. Linear discriminant analysis effect size (LEfSe) analysis showed a substantial decrease in abundance of the genus Faecalibacterium within the MG group. Fecal metabolome analysis identified three up-regulated metabolites involved in amino acid metabolism (taurine, creatinine, L-carnitine), one up-regulated metabolite involved in lipid metabolism (oleic acid), with correlation analysis indicating a positive association between Faecalibacterium abundance and creatinine levels. Conclusion: Our findings suggest that dysbiosis already exists in newly diagnosed and untreated MG patients, implying that dysbiosis within the gut microbiota may be an initiating factor contributing to MG pathogenesis. Furthermore, F. prausnitzii may hold promise as a probiotic for treating MG.