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Objectives: To evaluate and compare the accuracy of task-autonomous robot-assisted implant surgery (RAIS) and dynamic computer-assisted implant surgery (dCAIS) for zygomatic implant placement., Materials and Methods: Ten atrophic edentulous maxilla models requiring zygomatic implant (ZI) placement were randomly divided into the RAIS and dCAIS groups. Osteotomies and implant placement were performed under the guidance of a task-autonomous robotic system or dynamic navigation system. A total of 20 ZIs were analyzed. The angular, coronal, lateral coronal, coronal depth, apical, lateral apical, and apical depth deviations were measured and analyzed between the two groups. The primary outcome parameters were the angular deviations between the planned and the placed ZIs. Data was subjected to descriptive and comparative statistical analysis. The significance of inter-group differences for continuous variables was assessed with Student's two-sample t-tests, Welch two-sample t-tests, and Mann-Whitney U tests according to the distribution normality and variance homogeneity., Results: ZI placement deviations were compared between the RAIS and dCAIS groups, showing a mean angular deviation of 0.92 ± 0.40° versus 2.03 ± 0.53° (p < 0.001), a mean (±SD) coronal deviation of 0.48 ± 0.25 mm versus 1.29 ± 0.46 mm (p < 0.001), and a mean apical deviation of 0.88 ± 0.28 mm versus 1.96 ± 0.46 mm (p < 0.001)., Conclusions: For computer-guided ZI placement, task-autonomous RAIS was superior to dCAIS in terms of accuracy., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The learning curve effect of dynamic computer-assisted implant surgery (D-CAIS) was observed among inexperienced novice surgeons. The learning curves can provide valuable information for novice surgeons and valid comparisons between new and conventional techniques. Recently, robotic computer-assisted implant surgery (R-CAIS) has shown promise as a novel dental implant surgical technique for both partially and edentulous patients. However, its learning curve remains unknown., Purpose: The aim of this study was to explore the learning curve of dental implant placement surgery with a task-autonomous robotic system among young dentists with different specialties., Methods and Materials: Four young dentists (mean age: 25.3 ± 1.5 years at the beginning of their first attempt) with equal representation of males and females and with different specialties participated in this study. None of the participants had prior experience in R-CAIS. Each operator placed eight implants over eight attempts using a semi-active task-autonomous robotic system. Among the eight implants, four were straight lateral incisor implants, and four were 30°-tilted premolar implants. The implants were placed in each dental quadrant of the maxillary and mandibular jaw modules. The operation time was recorded. Coronal, apical, and angular deviations between the planned and actual sites of implant placement were measured by merging preoperative and postoperative cone-beam computed tomography (CBCT) scans. The data were analyzed with repeated-measures ANOVA (α = 0.05)., Results: The mean time for implant placement was associated with the number of attempts (p < 0.01). The time taken for the second attempt was significantly shorter than that of the first attempt (33.26 vs. 30.47 min; p < 0.001) then it plateaued. Three-dimensional (3D) angular (p = 0.31), coronal deviation (p = 0.26), and apical deviation (p = 0.06) did not differ significantly among attempts. The mean values and standard deviations of 3D coronal deviation, 3D apical deviation, and 3D angular deviation were 0.71 ± 0.31 mm, 0.72 ± 0.30 mm, and 0.94 ± 0.58°, respectively. Neither the position of the jaw (p > 0.59) nor the tilt angle of the implant (straight or 30°-tilted, p > 0.85) was related to implant placement accuracy., Conclusions: Dentists quickly learned the basic workflow of R-CAIS and thus facilitated the clinicians in the mastery of implant placement on edentulous jaw modules, leading to a comparable operating speed and high precision. Moreover, the accuracy of placement of straight and tilted implants in both the maxilla and mandible with R-CAIS was satisfactory., (© 2024 Wiley Periodicals LLC.)

Background: Early detection of nasopharyngeal carcinoma (NPC) patients who are not sensitive to neoadjuvant chemotherapy (NAC) can guard against overtreatment. This study aimed to evaluate the effectiveness of amide proton transfer (APT) imaging and diffusion-weighted imaging (DWI) in predicting the early response to NAC in patients with NPC., Methods: This prospective study enrolled fifty patients with biopsy-confirmed NPC from September 2021 to May 2023. Magnetic resonance imaging (MRI) including APT and DWI, was performed before NAC. After NAC, patients were divided into complete response (CR), partial response (PR), and stable disease (SD) and progressive disease (PD) groups based on the Response Evaluation Criteria in Solid Tumours Version 1.1. The Kruskal-Wallis H test was used for statistical analysis. The differences in APT and apparent diffusion coefficient (ADC) values among the different efficacy groups were compared, the receiver operating characteristic (ROC) curve was drawn for statistically significant parameters, and the area under the curve (AUC) was calculated., Results: Fifty patients (mean age: 47±14 years; 42 males and 8 females) were included in the final analysis (11 were in the CR group, 30 in the PR group, 9 in the SD group, and 0 in the PD group). The ADC values showed no significant differences among the different treatment response groups. The SD group showed significantly lower APT max (P=0.025), APT skewness (P=0.025) and APT 90% (P=0.001) values than the CR and PR groups. Setting APT 90% =3.10% as the cut-off value, optimal diagnostic performance (AUC: 0.831; sensitivity: 0.778; specificity: 0.878) was obtained in predicting the SD group., Conclusions: APT imaging can predict the early tumour response to NAC in patients with NPC. APT imaging may be superior to DWI in predicting tumour response., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-188/coif). Y.G. is from Central Research Institute, United Imaging Healthcare. The other authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Dynamic navigation-guided zygomatic implant (ZI) surgery has been a preferred option for achieving optimal prosthetic-driven implant placement. However, during the actual surgical procedure, surgical execution may still be hindered by environmental factors such as mouth opening. A fully digital planning protocol is described that integrated the patient's maxillofacial soft tissue information and virtual surgical handpiece with the drills on the implant planning path to ensure the precise, time-saving, and smooth implementation of dynamic navigation-guided ZI surgery., (Copyright © 2024 Editorial Council for The Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Morphine has been suggested to affect cancer cell dynamics and decrease survival rates in lung cancer patients at specific doses, but the precise mechanisms poorly understood. In this study, we aimed to investigate the molecular mechanisms by which morphine modulates the malignant characteristics of non-small cell lung cancer. Cell proliferation was assessed via the Cell Counting Kit-8 assay, and cell migration and invasion were examined via wound healing and Transwell assays. We employed immunofluorescence staining to evaluate E-cadherin expression in A549 and Lewis lung cancer (LLC) cell lines and immunohistochemistry to evaluate E-cadherin expression in nude mice tumours. Additionally, the in vivo effects of morphine on lung cancer progression were explored in a xenograft tumour experiments, in which naloxone was used as a morphine antagonist. Western blot analysis was performed to detect E-cadherin, phosphorylated mTOR (p-mTOR), mTOR, phosphorylated AKT (p-AKT), AKT, phosphorylated PI3K (p-PI3K), and PI3K protein levels in A549 and LLC cells as well as in tumour samples. Morphine (10 µM) significantly increased the proliferation of A549 and LLC cells in vitro (p < 0.05). It also enhanced the migratory and invasive capacities of these cell lines (p < 0.01). Mechanistically, morphine treatment (10 µM) led to a reduction in the expression of E-cadherin, and an increase in the phosphorylation of PI3K, AKT, and mTOR in A549 and LLC cells (p < 0.01). Morphine treatment (1.5 mg/kg) also reduced E-cadherin expression in xenograft tumours and promoted tumour growth in vivo (p < 0.05). This effect was reversed by naloxone (0.1 mg/kg). The results demonstrated that morphine stimulates the malignant proliferation of A549 and LLC cell lines and promotes xenograft tumour growth. Perhaps by specifically targeting MOR, morphine triggers a signalling cascade that activates the PI3K/AKT/mTOR pathway while inhibiting the EMT marker E-cadherin, which may consequently promote the progression of lung cancer., (© 2024. The Author(s).)

Background: Chitinase-3 like-protein-1 (CHI3L1) is a member of the mammalian chitinase-like proteins and elevated serum CHI3L1 level has been proved to be associated with poor prognosis in hepatocellular carcinoma (HCC). This study aimed to investigate the relationship between serum CHI3L1 levels and body composition parameters in patients with HCC after liver transplantation (LT)., Methods: This retrospective study enrolled 200 patients after LT for HCC. Blood samples were collected and serum concentrations of CHI3L1 were measured by enzyme-linked immunosorbent assay. Computer tomography (CT) were used to estimate skeletal muscle and adipose tissue mass. Spearman's rank correlation test was performed to assess associations between serum CHI3L1 levels and these body composition parameters. A Cox proportional-hazards regression model was performed to identify independent prognostic factors. Overall survival (OS) and recurrence-free survival (RFS) curves were constructed using the Kaplan-Meier method and compared by the log-rank test., Results: Total 71 patients (35.5%) were diagnosed with myosteatosis according to skeletal muscle radiation attenuation (SMRA). The 5-year OS rates were 66.9% in non-myosteatosis group, significantly higher than 49.5% in myosteatosis group (p = 0.025), while the RFS of myosteatosis group (5-year RFS: 52.6%) or non-myosteatosis group (5-year RFS: 42.0%) shown no significant difference (p = 0.068). The serum CHI3L1 level were significantly negative correlated with SMRA (r = -0.3, p < 0.001). Interestingly, in patients with myosteatosis, Kaplan-Meier analysis revealed that elevated serum CHI3L1 levels were associated with worse OS (p < 0.001) and RFS (p = 0.047). However, in patients without myosteatosis, Kaplan-Meier analysis found elevated serum CHI3L1 levels were not associated with OS (p = 0.070) or RFS (p = 0.104)., Conclusions: Elevated CHI3L1 was negatively correlated with SMRA, and predicted poorer prognosis in Chinese population after LT for HCC, especially in those patients with concomitant myosteatosis. Monitoring serum CHI3L1 can predict prognosis and effectively guide individual nutrition intervention., (© 2024. The Author(s).)

Objectives: The aim of this study was to compare the accuracy of dental implant placement in a single tooth gap, including the postextraction site and healed site, using a task-autonomous robotic system and a dynamic navigation system., Materials and Methods: Forty partially edentulous models requiring both immediate and conventional implant placement were randomly divided into a robotic system group and a navigation system group. The coronal, apical, and angular deviations of the implants were measured and assessed between the groups., Results: The deviations in immediate implant placement were compared between the robotic system and dynamic navigation system groups, showing a mean (±SD) coronal deviation of 0.86 ± 0.36 versus 0.70 ± 0.21 mm (p = .101), a mean apical deviation of 0.77 ± 0.34 versus 0.95 ± 0.38 mm (p = .127), and a mean angular deviation of 1.94 ± 0.66° versus 3.44 ± 1.38° (p < .001). At the healed site, significantly smaller coronal deviation (0.46 ± 0.29 vs. 0.70 ± 0.30 mm, p = .005), apical deviation (0.56 ± 0.30 vs. 0.85 ± 0.25 mm, p < .001), and angular deviation (1.36 ± 0.54 vs. 1.80 ± 0.70 mm, p = .034) were found in the robotic system group than in the dynamic navigation group., Conclusions: The position in both immediate and conventional implant placement was more precise with the task-autonomous robotic system than with the dynamic navigation system. Its performance in actual clinical applications should be confirmed in further trials., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Utilizing spontaneous polarization field to harness charge transfer kinetics is a promising strategy to boost photocatalytic performance. Herein, a novel Cu atom clusters/PtCu alloy nanocubes coloaded on nitrogen-rich triazole-based C 3 N 5 (PtCu-C 3 N 5 ) with dipole field was constructed through facile photo-deposition and impregnation method. The dipole field-drive spontaneous polarization in C 3 N 5 acts as a charge-transfer bridge to promote directional electron migration from C 3 N 5 to Cu atom clusters/PtCu alloy. Through the synergistic effects between Cu atom clusters, PtCu alloy and dipole field in C 3 N 5 , the optimized Pt 2 Cu 3 -C 3 N 5 achieved a record-high performance with H 2 formation rate of 4090.4 μmol g -1  h -1 under visible light, about 154.4-fold increase compared with pristine C 3 N 5 (26.5 μmol g -1  h -1 ). Moreover, the apparent quantum efficiency was up to 25.33 % at 320 nm, which is greatly superior than most previous related-works. The directional charge transfer mechanism was analyzed in detail through various characterizations and DFT calculations. This work offers a novel pathway to construct high-efficiency multi-metal photocatalysts for solar energy conversion., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The purpose of this study is to systematically analyze the development trend, research hotspots, and future development direction on the treatment of neuropathic pain (NP) with spinal cord stimulation through bibliometric method. We extracted the literature related to the treatment of NP with spinal cord stimulation from January 2004 to December 2023 from the Web of Science database. As a result, a total of 264 articles were retrieved. By analyzing the annual published articles, authors, countries, institutions, journals, co-cited literature, and keywords, we found that the count of publication in this field has been experiencing an overall growth, and the publications within the past 5 years accounted for 42% of the total output. Experts from the United States and the UK have made significant contributions in this field and established a stable collaborative team, initially establishing an international cooperation network. Pain is the frequently cited journal in this field. The study on spinal cord stimulation therapy for NP especially the study on spinal cord stimulation therapy for back surgery failure syndrome (FBSS) and its potential mechanisms are the research hotspots in this field, while the study on novel paradigms such as high-frequency spinal cord stimulation and spinal cord burst stimulation represents the future development directions. In short, spinal cord stimulation has been an effective treatment method for NP. The novel paradigms of spinal cord stimulation are the key point of future research in this field., (© 2024. The Author(s).)

Inhibiting the death receptor 3 (DR3) signaling pathway in group 3 innate lymphoid cells (ILC3s) presents a promising approach for promoting mucosal repair in individuals with ulcerative colitis (UC). Paeoniflorin, a prominent component of Paeonia lactiflora Pall., has demonstrated the ability to restore barrier function in UC mice, but the precise mechanism remains unclear. In this study, we aimed to delve into whether paeoniflorin may promote intestinal mucosal repair in chronic colitis by inhibiting DR3 signaling in ILC3s. C57BL/6 mice were subjected to random allocation into 7 distinct groups, namely the control group, the 2 % dextran sodium sulfate (DSS) group, the paeoniflorin groups (25, 50, and 100 mg/kg), the anti-tumor necrosis factor-like ligand 1A (anti-TL1A) antibody group, and the IgG group. We detected the expression of DR3 signaling pathway proteins and the proportion of ILC3s in the mouse colon using Western blot and flow cytometry, respectively. Meanwhile, DR3-overexpressing MNK-3 cells and 2 % DSS-induced Rag1 -/- mice were used for verification. The results showed that paeoniflorin alleviated DSS-induced chronic colitis and repaired the intestinal mucosal barrier. Simultaneously, paeoniflorin inhibited the DR3 signaling pathway in ILC3s and regulated the content of cytokines (Interleukin-17A, Granulocyte-macrophage colony stimulating factor, and Interleukin-22). Alternatively, paeoniflorin directly inhibited the DR3 signaling pathway in ILC3s to repair mucosal damage independently of the adaptive immune system. We additionally confirmed that paeoniflorin-conditioned medium (CM) restored the expression of tight junctions in Caco-2 cells via coculture. In conclusion, paeoniflorin ameliorates chronic colitis by enhancing the intestinal barrier in an ILC3-dependent manner, and its mechanism is associated with the inhibition of the DR3 signaling pathway., Competing Interests: The authors declare that there are no conflicts of interest., (© 2024 The Authors.)

Smad-ubiquitination regulator 2 (SMURF2) functions as a homolog of E6AP carboxyl terminus-type E3 ubiquitin ligase to regulate cell cycle progression and tumor growth factor expression. SMURF2 has been revealed to function as a tumor suppressor in a number of cancers; however, its function in papillary thyroid carcinoma (PTC) remains largely unknown. Therefore, the aim of the present study was to investigate the function of SMURF2 in PTC. Reverse transcription-quantitative PCR and western blotting were used to detect cellular expression of SMURF2 in vitro . After increasing or inhibiting the expression of SMURF2, MTT was used to detect the effect on tumor cell proliferation and Transwell assays were used to detect the effect on tumor cell migration and invasion. Finally, ELISA was used to detect the effects on glucose and glutamine metabolism in tumor cells and the findings revealed that SMURF2 was downregulated in PTC tissues. Moreover, SMURF2 inhibited the proliferation, invasion and migration of PTC cells, and promoted their apoptosis. Finally, SMURF2 inhibited cell glycolysis and glutaminolysis and affected metabolism in the PTC cell line, TPC-1. Thus, the findings of the present study suggest that SMURF2 may be a potential target in the treatment of PTC., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2024, Spandidos Publications.)

Fatty liver hemorrhagic syndrome (FLHS) is a prevalent metabolic disorder observed in egg-laying hens, characterized by fatty deposits and cellular steatosis in the liver. Our preliminary investigations have revealed a marked decrease in the concentration of butyric acid in the FLHS strain of laying hens. It has been established that sodium butyrate (NaB) protects against metabolic disorders. However, the underlying mechanism by which butyrate modulates hepato-lipid metabolism to a great extent remains unexplored. In this study, we constructed an isolated in vitro model of chicken primary hepatocytes to induce hepatic steatosis by free fatty acids (FFA). Our results demonstrate that treatment with NaB effectively mitigated FFA-induced hepatic steatosis in chicken hepatocytes by inhibiting lipid accumulation, downregulating the mRNA expression of lipo-synthesis-related genes (sterol regulatory element binding transcription factor 1 (SREBF1), acetyl-CoA carboxylase 1(ACC1), fatty acid synthase (FASN), stearoyl-CoA desaturase 1 (SCD1), liver X receptor α (LXRα), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR)) (P < 0.05), and upregulating the mRNA and protein expression of AMP-activated protein kinase α1 (AMPKα1), peroxisome proliferator-activated receptor α (PPARα), and carnitine palmitoyl-transferase 1A (CPT1A) (P < 0.05). Moreover, AMPK and PPARα inhibitors (Compound C (Comp C) and GW6471, respectively) reversed the protective effects of NaB against FFA-induced hepatic steatosis by blocking the AMPK/PPARα pathway, leading to lipid droplet accumulation and triglyceride (TG) contents in chicken primary hepatocytes. With these findings, NaB can alleviate hepatocyte lipoatrophy injury by activating the AMPK/PPARα pathway, promoting fatty acid oxidation, and reducing lipid synthesis in chicken hepatocytes, potentially being able to provide new ideas for the treatment of FLHS., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Highly active hepatitis B virus (HBV) is known to be associated with poor outcomes in patients with hepatocellular carcinoma (HCC). This study aims to investigate the relationship between HBV status and HCC recurrence after liver transplantation., Methods: The study retrospectively analyzed HCC patients undergoing liver transplantation in two centres between January 2015 and December 2020. The authors reviewed post-transplant HBV status and its association with outcomes., Results: The prognosis of recipients with hepatitis B surface antigen (HBsAg) reappearance ( n =58) was poorer than those with HBsAg persistent negative ( n =351) and positive ( n =53). In HBsAg persistent positive group, recipients with HBV DNA reappearance or greater than 10-fold increase above baseline had worse outcomes than those without ( P <0.01). HBV reactivation was defined as (a) HBsAg reappearance or (b) HBV DNA reappearance or greater than 10-fold increase above baseline. After propensity score matching, the 5-year overall survival rate and recurrence-free survival rate after liver transplantation in recipients with HBV reactivation were significantly lower than those without (32.0% vs. 62.3%; P <0.01, and 16.4% vs. 63.1%; P <0.01, respectively). Moreover, HBV reactivation was significantly related to post-transplant HCC recurrence, especially lung metastasis. Cox regression analysis revealed that beyond Milan criteria, microvascular invasion and HBsAg-positive graft were independent risk factors for post-transplant HBV reactivation, and a novel nomogram was established accordingly with a good predictive efficacy (area under the time-dependent receiver operating characteristic curve=0.78, C-index =0.73)., Conclusions: Recipients with HBV reactivation had worse outcomes and higher tumour recurrence rates than those without. The nomogram could be used to evaluate the risk of post-transplant HBV reactivation effectively., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Aims/introduction: The coronary physiology and prognosis of patients with different hemoglobin A1c (HbA1c) levels after percutaneous coronary intervention (PCI) are currently unknown. The aim of this study was to assess the effect of different levels of HbA1c control on coronary physiology in patients who underwent PCI for coronary heart disease combined with type 2 diabetes mellitus by quantitative flow ratio (QFR)., Materials and Methods: Patients who successfully underwent PCI and completed 1-year coronary angiographic follow up were enrolled, clinical data were collected, and QFR at immediate and 1-year follow up after PCI was retrospectively analyzed. A total of 257 patients (361 vessels) were finally enrolled and divided into the hemoglobin A1c (HbA1c)-compliance group (103 patients, 138 vessels) and non-HbA1c-compliance group (154 patients, 223 vessels) according to the HbA1c cut-off value of 7%. We compared the results of QFR analysis and clinical outcomes between the two groups., Results: At 1-year follow up after PCI, the QFR was significantly higher (0.94 ± 0.07 vs 0.92 ± 0.10, P = 0.019) and declined less (0.014 ± 0.066 vs 0.033 ± 0.095, P = 0.029) in the HbA1c-compliance group. Meanwhile, the incidence of physiological restenosis was lower in the HbA1c-compliance group (2.9% vs 8.5%, P = 0.034). Additionally, the target vessel revascularization rate was lower in the HbA1c-compliance group (6.8% vs 16.9%, P = 0.018). Furthermore, HbA1c ≥7% (OR 2.113, 95% confidence interval 1.081-4.128, P = 0.029) and QFR decline (OR 2.215, 95% confidence interval 1.147-4.277, P = 0.018) were independent risk factors for target vessel revascularization., Conclusion: Patients with well-controlled HbA1c levels have better coronary physiological benefits and the incidence of adverse clinical outcome events might be reduced., (© 2023 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Di-(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer known for its environmental endocrine-disrupting properties, posing potential risks to various organs. However, the precise impact of DEHP on intestinal health and its contribution to the initiation of intestinal inflammation remains elucidated. This study aims to investigate the underlying mechanisms of DEHP-induced intestinal inflammation in mice, specifically focusing on the complex interplay between the gut microbiota-metabolite axis and associated pathophysiological alterations. Our findings showed that DEHP-induced damage of multiple organs systemically, as indicated by abnormal liver and kidney biochemical markers, along with a disrupted ileum morphology. Additionally, DEHP exposure disrupted gut barrier function, causing intestinal inflammation characterized by bacterial translocation and alterations in defense and inflammation-related gene expressions. Moreover, 16S rRNA analysis suggested that DEHP-induced gut microbial remodeling is characterized by an upregulation of detrimental bacteria (Erysipelotrichaceae) and a downregulation of beneficial bacteria (Muribaculaceae, Ruminococcaceae, and Lachnospiraceae). Metabolomics analysis revealed DEHP perturbed gut metabolic homeostasis, particularly affecting the degradation of aromatic compounds, which generated an aberrant activation of the AhR and NF-κB, subsequently causing intestinal inflammation. Consequently, our results elucidate the mechanistic link between disrupted gut microbiota and metabolome and the initiation of DEHP-induced intestinal inflammation, mediated through the AhR/NF-κB signaling pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Atrazine (ATR), a water-soluble herbicide commonly used to control broad-leaf and monocotyledonous weeds, presents a significant risk to environmental soil and water quality. Exposure to ATR adversely affects human and animal health, frequently resulting in cardiac impairment. Curcumin (Cur), an acidic polyphenol derivative from plants acclaimed for its pronounced anti-inflammatory and antioxidant properties, has garnered interest as a potential therapeutic agent. However, whether it has the potential to ameliorate ATR-induced cardiac toxicity via modulation of endoplasmic reticulum stress (ERS) and apoptosis pathways in mice remains unclear. Our results showed that Cur supplementation attenuates ATR-induced cardiotoxicity, evidenced by decrease in creatine kinase and lactate dehydrogenase, key biochemical markers of myocardial injury, which have a more significant protecting effect in high-dose ATR induced injury. Histopathological and electron microscopy examinations further solidified these findings, demonstrating an amelioration in organellar damage, particularly in endoplasmic reticulum swelling and subsequent mitochondrial impairment. Additionally, ATR exposure augments ERS and triggers apoptotic pathways, as indicated by the upregulation of ERS-related gene expression (ATF6, CHOP, IRE1, GRP78) and pro-apoptotic markers (BAX, BAK1, Caspase3, Caspase. Intriguingly, Cur counteracts this detrimental response, significantly reducing ERS and pro-apoptotic signals at both transcriptional and translational levels. Collectively, our findings illuminate Cur's cardioprotective effect against ATR-induced injury, primarily through its anti-ERS and anti-apoptotic activities, underscoring Cur's potential as a therapeutic for ATR-induced cardiotoxicity., Competing Interests: Declaration of Competing Interest The authors declare no other conflict of interest., (Copyright © 2024. Published by Elsevier Masson SAS.)

Lysosomal dysfunction can drive carcinogenesis. Lysosomal-associated membrane protein 3 (LAMP3), is a member of the Lysosome Associated Membrane Proteins and is involved in the malignant phenotype such as tumour metastasis and drug resistance, while the mechanisms that regulate the malignant progression of tumour remain vague. Our study aims to provide a more systematic and comprehensive understanding of the role of LAMP3 in the progression of various cancers by various databases.We explored the role of LAMP3 in pan-cancer using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database. Multiple online web platforms and software were used for data analysis, including HPA, TIMER, TISIDB, GEPIA, UALCAN, Kaplan-Meier plotter, DAVID and TIGER. The immunohistochemistry was used to quantify the LAMP3 and PD-L1 expression levels in cancer.High LAMP3 expression was found in most cancers and differentially expressed across molecular and immune subtypes. The expression of LAMP3 was involved in the immune-associated processes of Antigen processing and presentation, Th17 cell differentiation, Th1 and Th2 cell differentiation, and the immune-associated pathways of T cell receptor and B cell receptor signalling pathways in most cancers. It also correlated with genetic markers of immunomodulators in various cancers. LAMP3 and PD-L1 expression in BRCA and HNSC tissues was higher than that in corresponding adjacent normal tissues by immunohistochemistry. There is a significant correlation between the expression of LAMP3 and PD-L1.Our study elucidates that LAMP3 has different expression patterns and genetic alteration patterns in different tumours. It is a potential biomarker for immune-related cancer diagnosis, prognosis and efficacy prediction., (© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Fatty liver hemorrhagic syndrome (FLHS) in laying hens is a nutritional metabolic disease commonly observed in high-yielding laying hens. Sodium butyrate (NaB) and ferroptosis were reported to contribute to the pathogenesis of fatty liver-related diseases. However, the underlying mechanism of NaB in FLHS and whether it mediates ferroptosis remains unclear. A chicken primary hepatocyte induced by free fatty acids (FFAs, keeping the ratio of sodium oleate and sodium palmitate concentrations at 2:1) was established, which received treatments with NaB, the ferroptosis inducer RAS-selective lethal 3 (RSL3), and the inhibitor ferrostatin-1 (Fer-1). As a result, NaB increased biochemical and lipid metabolism indices, and the antioxidant level, while inhibiting intracellular ROS accumulation and the activation of the ferroptosis signaling pathway, as evidenced by a reduction in intracellular iron concentration, upregulated GPX4 and xCT expression, and inhibited NCOA4 and ACSL4 expression. Furthermore, treatment with Fer-1 reinforced the protective effects of NaB, while RSL3 reversed it by blocking the ROS/GPX4/ferroptosis pathway, leading to the accumulation of lipid droplets and oxidative stress. Collectively, our findings demonstrated that NaB protects hepatocytes by regulating the ROS/GPX4-mediated ferroptosis pathway, providing a new strategy and target for the treatment of FLHS.

Neuroinflammation plays a key role in early brain injury (EBI) of subarachnoid hemorrhage (SAH), and NLRP3 inflammasome plays an important role in the development of neuroinflammation after SAH, but the mechanism of NLRP3 inflammasome activation after SAH is still unclear. TRPV1 is a non-selective calcium channel that is involved in the pathology of neuroinflammation, but its role in SAH has not been revealed. Our study showed that TRPV1 was significantly upregulated after SAH and was predominantly expressed in microglia/macrophages. Antagonism of TRPV1 was effective in ameliorating neurological impairment, brain edema, neuronal damage, and reducing the inflammatory response (evidenced by reducing the number of CD16/32 positive microglia/macrophages, inhibiting the expression of CD16, CD32, CD86, IL-1b, TNF-a and blocking NLRP3 inflammasome activation). However, this effect can be abolished by NLRP3 inflammasome antagonist MCC950. In vitro experiment confirmed that TRPV1 activated NLRP3 inflammasome by increasing intracellular calcium levels. In conclusion, TRPV1 mediates EBI after SAH via calcium/NLRP3, and TRPV1 is a potential therapeutic target after SAH.

Triclosan (TCS) is an antimicrobial compound incorporated into more than 2000 consumer products. This compound is frequently detected in the human body and causes ubiquitous contamination in the environment, thereby raising concerns about its impact on human health and environmental pollution. Here, we demonstrated that 20 weeks' exposure of TCS drove the development of glucose intolerance by inducing compositional and functional alterations in intestinal microbiota in rats. Fecal-transplantation experiments corroborated the involvement of gut microbiota in TCS-induced glucose-tolerance impairment. 16S rRNA gene-sequencing analysis of cecal contents showed that TCS disrupted the gut microbiota composition in rats and increased the ratio of Firmicutes to Bacteroidetes. Cecal metabolomic analyses detected that TCS altered host metabolic pathways that are linked to host glucose and amino acid metabolism, particularly branched-chain amino acid (BCAA) biosynthesis. BCAA measurement confirmed the increase in serum BCAAs in rats exposed to TCS. Western blot and immunostaining results further confirmed that elevated BCAAs stimulated mTOR, a nutrient-sensing complex, and following IRS-1 serine phosphorylation, resulted in insulin resistance and glucose intolerance. These results suggested that TCS may induce glucose metabolism imbalance by regulating BCAA concentration by remodeling the gut microbiota., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Ulcerative colitis (UC) pathogenesis is largely associated with intestinal epithelial barrier dysfunction. A therapeutic approach to UC involves the repair of damaged intestinal barrier. Our study aimed to investigate whether aryl hydrocarbon receptor (AhR) mediated the intestinal barrier repair effects of quercetin to ameliorate UC. 3% dextran sulfate sodium was used to induce colitic mice, and quercetin (25, 50, and 100 mg/kg) was administered orally for 10 days to assess the therapeutic effects. In vitro, Caco-2 cells were used to explore the effect of quercetin on tight junction protein expression and AhR activation. The results showed that quercetin alleviated colitic mice by restoring tight junctions (TJs) integrity via an AhR-dependent manner (p < 0.05). In vitro, quercetin dose-dependently elevated the expressions of TJs protein ZO-1 and Claudin1, and activated AhR by enhancing the expression of CYP1A1 and facilitating AhR nuclear translocation in Caco-2 cells (p < 0.05). While AhR antagonist CH223191 reversed the therapeutic effects of quercetin (p < 0.05) and blocked quercetin-induced AhR activation and enhancement of TJs protein (p < 0.05). In conclusion, quercetin repaired intestinal barrier dysfunction by activating AhR-mediated enhancement of TJs to alleviate UC. Our research offered new perspectives on how quercetin enhanced intestinal barrier function., (© 2023 John Wiley & Sons Ltd.)

Berberine (BBR) is a natural alkaloid with multiple biotical effects that has potential as a treatment for fatty liver hemorrhagic syndrome (FLHS). However, the mechanism underlying the protective effect of BBR against FLHS remains unclear. The present study aimed to investigate the effect of BBR on FLHS induced by a high-energy, low-protein (HELP) diet and explore the involvement of the gut microbiota and bile acid metabolism in the protective effects. A total of 90 healthy 140-day-old Hy-line laying hens were randomly divided into three groups, including a control group (fed a basic diet), a HELP group (fed a HELP diet), and a HELP+BBR group (high-energy, high-protein diet supplemented with BBR instead of maize). Our results show that BBR supplementation alleviated liver injury and hepatic steatosis in laying hens. Moreover, BBR supplementation could significantly regulate the gut's microbial composition, increasing the abundance of Actinobacteria and Romboutsia. In addition, the BBR supplement altered the profile of bile acid. Furthermore, the gut microbiota participates in bile acid metabolism, especially taurochenodeoxycholic acid and α-muricholic acid. BBR supplementation could regulate the expression of genes and proteins related to glucose metabolism, lipid synthesis (FAS, SREBP-1c), and bile acid synthesis (FXR, CYP27a1). Collectively, our findings demonstrate that BBR might be a potential feed additive for preventing FLHS by regulating the gut microbiota and bile acid metabolism.

Background: In the context of global aging, the characteristics of chronic diseases seriously affect the quality of life of older adults. It is urgent to carry out continuous nursing basis for older adult patients with chronic diseases. In view of the remarkable efficacy of Chinese medicine in the treatment of chronic diseases, this study may help to understand the demand for "Internet + Chinese medicine" home care service and its influencing factors of older adult chronic disease patients, and to provide a reference basis for improving the quality of life of the older adult chronic disease population., Methods: This is a mixed study. The quantitative study adopted the convenience sampling method, and a total of 308 patients in a third-grade hospital in Shaanxi Province were investigated by general data questionnaire, traditional Chinese medicine service demand questionnaire, traditional Chinese medicine knowledge questionnaire, older adult Chinese medicine attitude questionnaire, and home care demand questionnaire from March to April 2022. In the qualitative study, semi-structured interviews were adopted, and patients were interviewed until the content was saturated. Colaizzi analysis method was used to analyze and summarize the topic of the interview data., Results: 308 valid questionnaires were collected, and the patients scored (58.42 ± 17.16) on the demand for TCM nursing services, (59.86 ± 11.54) on the knowledge of TCM, (73.03 ± 9.11) on the attitude toward TCM, and (136.84 ± 46.39) on the demand for home care. The results of multiple linear regression showed that learning about the nursing service pathway, knowledge of general knowledge of Chinese medicine, and attitude toward Chinese medicine among the older adult and home care demand were the influencing factors of the demand for Chinese medicine nursing services for older adult patients with chronic diseases ( p  < 0.05). The results of the in-depth interviews were summarized into three themes: facilitating factor, hindering factor, and the "Internet + Chinese medicine" multiple needs of home care., Conclusion: Older adult patients with chronic diseases have a high intention of home care demand and they are affected by multiple factors. Consequently, the actual demand situation of older adult patients with chronic diseases should be used as a guide to provide directed and diversified Chinese medicine home care services to meet the individualized needs of the older adult., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Chen, Feng, Zhuang, Wang, Zhang, Liu and Chen.)

Background: Postoperative delirium (POD) is a common clinical complication in elderly patients after surgery and predicts poor outcomes., Aim: We researched whether postoperative infusion of dexmedetomidine (DEX) had prophylactic effect on POD in elderly patients., Methods: A total of 236 patients over the age of 60 years undergoing thoracoabdominal tumor surgery were enrolled in Zhejiang Cancer Hospital from November 2016 to October 2020. The patients were randomly assigned into DEX group (group D) and control group (Group C). DEX was provided via PCIA pump 1-3 days after surgery, which consisted of 3 ug/kg sufentanil and 3 ug/kg DEX in group D, and 3 ug/kg sufentanil without DEX in group C. The PCIA parameters were programmed as follows: total amount 150 ml, 2 ml bolus dose with a lock-out of 10 min and background infusion rate 2 ml/h. The primary endpoint was the incidence of POD, assessed twice daily within 7 days after surgery by Richmond Agitation-Sedation Scale (RASS) and the Confusion Assessment Method-Intensive Care Unit (CAM-ICU). The secondary endpoint was postoperative hospitalization days, ICU stay time, adverse events and non-delirium complications., Results: The incidence of POD in all patients was 7%. The incidence of POD in group C was significantly higher than that in group D (10.1% vs 3.4%, P = 0.042). There were no significant differences in length of hospital stay after operation, ICU stay time, the percentage of patients discharged within 7 days after surgery, non-delirium complications, and 30-day all-cause deaths between the two groups. The incidence of hypertension in group D was lower than that in group C (P = 0.003), and there were no differences in other adverse events., Conclusion: Patients aged over 60 years received DEX in addition to intravenous patient-controlled analgesia (PCIA) for major thoracoabdominal surgery experienced less delirium., (© 2023. The Author(s).)

Background The renin-angiotensin system plays a crucial role in the development of heart failure, and Ang II (angiotensin II) acts as the critical effector of the renin-angiotensin system in regulating cardiac fibrosis. However, the mechanisms of cardiac fibrosis are complex and still not fully understood. IGF1R (insulin-like growth factor 1 receptor) has multiple functions in maintaining cardiovascular homeostasis, and low-dose IGF1 treatment is effective in relieving Ang II-induced cardiac fibrosis. Here, we aimed to investigate the molecular mechanism of IGF1R in Ang II-induced cardiac fibrosis. Methods and Results Using primary mouse cardiac microvascular endothelial cells and fibroblasts, in vitro experiments were performed. Using C57BL/6J mice and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9)-mediated IGF1R heterozygous knockout ( Igf1r +/- ) mice, cardiac fibrosis mouse models were induced by Ang II for 2 weeks. The expression of IGF1R was examined by quantitative reverse transcription polymerase chain reaction, immunohistochemistry, and Western blot. Mice heart histologic changes were evaluated using Masson and picro sirius red staining. Fibrotic markers and signal molecules indicating the function of the Akt (protein kinase B)/ERK (extracellular signal-regulated kinase)/nuclear factor-κB pathway were detected using quantitative reverse transcription polymerase chain reaction and Western blot. RNA sequencing was used to explore IGF1R-mediated target genes in the hearts of mice, and the association of IGF1R and G-protein-coupled receptor kinase 5 was identified by coimmunoprecipitation. More important, blocking IGF1R signaling significantly suppressed endothelial-mesenchymal transition in primary mouse cardiac microvascular endothelial cells and mice in response to transforming growth factor-β1 or Ang II, respectively. Deficiency or inhibition of IGF1R signaling remarkably attenuated Ang II-induced cardiac fibrosis in primary mouse cardiac fibroblasts and mice. We further observed that the patients with heart failure exhibited higher blood levels of IGF1 and IGF1R than healthy individuals. Moreover, Ang II treatment significantly increased cardiac IGF1R in wild type mice but led to a slight downregulation in Igf1r +/- mice. Interestingly, IGF1R deficiency significantly alleviated cardiac fibrosis in Ang II-treated mice. Mechanistically, the phosphorylation level of Akt and ERK was upregulated in Ang II-treated mice, whereas blocking IGF1R signaling in mice inhibited these changes of Akt and ERK phosphorylation. Concurrently, phosphorylated p65 of nuclear factor-κB exhibited similar alterations in the corresponding group of mice. Intriguingly, IGF1R directly interacted with G-protein-coupled receptor kinase 5, and this association decreased ≈50% in Igf1r +/- mice. In addition, Grk5 deletion downregulated expression of the Akt/ERK/nuclear factor-κB signaling pathway in primary mouse cardiac fibroblasts. Conclusions IGF1R signaling deficiency alleviates Ang II-induced cardiac fibrosis, at least partially through inhibiting endothelial-mesenchymal transition via the Akt/ERK/nuclear factor-κB pathway. Interestingly, G-protein-coupled receptor kinase 5 associates with IGF1R signaling directly, and it concurrently acts as an IGF1R downstream effector. This study suggests the promising potential of IGF1R as a therapeutic target for cardiac fibrosis.

Hematoma-induced neuroinflammation is the cause of poor prognosis in intracerebral hemorrhage (ICH); therefore, promoting blood clearance and blocking overactivated inflammation are rational approaches for ICH treatment. β-site amyloid precursor protein (APP) lyase-1 (BACE1) is a key molecule regulating the microglial phenotype transition in neurodegenerative diseases. Therefore, the aim of this study was to investigate the role of BACE1 in microglial phagocytosis and inflammatory features in ICH. Here, we demonstrated the unique advantages of targeting BACE1 in microglia using an autologous blood model and primary microglia hemoglobin stimulation. When BACE1 was inhibited early in ICH, fewer residual hematomas remained, consistent with an increase in genetic features that favor phagocytosis and anti-inflammation. In addition, inhibition of BACE1 enhanced the secretion of anti-inflammatory cytokines and substantially reduced the expression of proinflammatory genes, which was regulated by signal transduction and phosphorylation of activator of transcription 3 (STAT3). Further pharmacological inhibition of STAT3 phosphorylation effectively blocked the proinflammatory and weak phagocytic phenotype of microglia due to BACE1 induction. In summary, BACE1 is the critical molecule regulating the inflammatory and phagocytic phenotypes of microglia after ICH, and targeted inhibition of the BACE1/STAT3 pathway is an important strategy for the future treatment of ICH-induced neurological injury.

Aberrant ubiquitination contributes to cancer development, including thyroid carcinoma. The present study assessed the expression of ubiquitin carboxy-terminal hydrolase 47 (USP47) and underlying molecular events in the development of papillary thyroid carcinoma (PTC). The effects of USP47 on PTC cell invasion and migration were analyzed by Transwell assays, while. the effects of USP47 and SATB1on PTC cell gene expression and changes in tumor cell metabolism were assayed by reverse transcription-quantitative PCR, western bolt, or ELISA, respectively. The expression of USP47 mRNA and protein was upregulated in PTC tissue and associated with the PTC tumor size. Knockdown of USP47 expression in PTC cell lines (TPC-1 and K1), decreased the cell proliferation mobility and invasion capacities, whereas USP47 overexpression in these cell lines showed an inverse effect and promoted cell glycolysis and glutamine metabolism. Moreover, expression of special AT-rich sequence-binding protein-1 (SATB1) was high in PTC tissue and was associated with USP47 expression. SATB1 expression promoted tumor cell glycolysis and glutamine metabolism, while USP47 protein bound to and deubiquitinated SATB1 to increase its intracellular levels, thus promoting glycolysis and glutamine metabolism. USP47 promotion of PTC development may be due to its stabilization of SATB1 protein, suggesting that targeting the USP47/SATB1 signaling axis may serve as a therapeutic intervention for PTC., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2023, Spandidos Publications.)

Background: The single port surgical robot causes only one incision and brings many benefits to patients. It is very challenging to design a single port surgical robot that causes a smaller incision than current products., Methods: This paper presents a highly compact single port laparoscopy surgical robot, which makes full use of the space of the port and only needs a 15 mm-diameter port. The robot is composed of a camera manipulator and two operating manipulators. The non-fully cylindrical manipulators enter the port sequentially, and the equivalent diameter of each operating manipulator is 12 mm. An additional 9 mm-diameter channel is left for other surgical tools to pass through after all manipulators entering the port., Results: The kinematics model of the robot is established, including detailed forward kinematics model and inverse kinematics solution based on geometric iteration method. The teleoperation experiment shows that the manipulator can complete the object-grasping, object-transfer and weight-lifting tasks., Conclusions: The proposed single port surgical robot design concept can also be extended to the field of natural orifice transluminal endoscopic surgical robots., (© 2022 John Wiley & Sons Ltd.)

Objectives: To develop a novel analytical approach based on 18 F-fluorodeoxyglucose ([ 18 F]FDG) positron emission tomography (PET) metabolic parameters, serum inflammatory markers, and clinical variables to improve the outcome prediction in NSCLC., Methods: A total of 190 newly diagnosed NSCLC patients who underwent pretreatment [ 18 F]FDG PET/CT were retrospectively enrolled and divided into a training cohort (n = 127) and a test cohort (n = 63). Cox regression analysis was used to investigate the predictive values of PET metabolic parameters, inflammation markers, and clinical variables for progression-free survival (PFS) and overall survival (OS). Based on the results of multivariate analysis, PET-based, clinical, and combined models were constructed. The predictive performance of different models was evaluated using time-dependent ROC curve analysis, Harrell concordance index (C-index), calibration curve, and decision curve analysis., Results: The combined models incorporating SULmax, MTV, NLR, and ECOG PS demonstrated significant prognostic superiority over PET-based models, clinical models, and TNM stage in terms of both PFS (C-index: 0.813 vs. 0.786 vs. 0.776 vs. 0.678, respectively) and OS (C-index: 0.856 vs. 0.792 vs. 0.781 vs. 0.674, respectively) in the training cohort. Similar results were observed in the test cohort for PFS (C-index: 0.808 vs. 0.764 vs. 0.748 vs. 0.679, respectively) and OS (C-index: 0.836 vs. 0.785 vs. 0.726 vs. 0.660, respectively) prediction. The combined model calibrated well in two cohorts. Decision curve analysis supported the clinical utility of the combined model., Conclusions: We reported a novel analytical approach combining PET metabolic information with inflammatory biomarker and clinical characteristics, which could significantly improve outcome prediction in newly diagnosed NSCLC., Key Points: • The nomogram incorporating SULmax, MTV, NLR, and ECOG PS outperformed the TNM stage for outcome prediction in patients with newly diagnosed NSCLC. • The established nomogram could provide refined prognostic stratification., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Ethnopharmacological Relevance: Gegen Qinlian decoction (GQD) is a traditional Chinese medicine derived from Treatise on febrile diseases and is clinically used for the treatment of acute ulcerative colitis (UC). However, the potential mechanism of GQD treatment for UC remains elusive., Aim of Study: In this study, we aimed to explore the involvement of gut microbiota-related tryptophan metabolism in mediating protective effects of GQD against intestinal barrier damage., Materials and Methods: Mice with colitis were treated with 3% dextran sulfate sodium (DSS) for 6 days. The therapeutic effects of GQD in UC mice were examined based on body weight, disease activity index (DAI), organ index, length and pathological changes in the colon. The distribution of fluorescein isothiocyanate dextran (FITC-dextran) in the intestinal tract was observed using small animal imaging, while concentration of FITC-dextran in serum was detected using a fluorescein microplate analyser. Bacterial infiltration in colon tissues was observed by fluorescence in situ hybridisation (FISH), and the bacterial load in mesenteric lymph nodes (MLNs) was further examined through bacterial culture. Subsequently, colonic goblet cells were detected using Alcian blue staining. The tight junctions of the colonic epithelium were observed using transmission electron microscopy, and the expression of tight junction proteins was detected by immunofluorescence (IF) and western blot. In addition, flow cytometry was used to analyse the proportion of interleukin-22-positive (IL-22 + ) ILC3 cells in lamina propria lymphocytes, and the content of IL-22 in colon homogenates was determined using an ELISA kit. In addition, targeted tryptophan metabolomics was used to detect the concentration of indole derivatives produced by tryptophan metabolism in faeces, and 16S rDNA was used to investigate the composition and abundance of gut microbiota-related tryptophan metabolism., Results: Administration of GQD significantly alleviated the pathological symptoms, including weight loss, increased DAI score, changes in organ index, colon shortening, and colon pathological injury in UC mice. In addition, GQD reduced the diffusion of FITC-dextran in the intestinal tract, the content of FITC-dextran in serum, and bacterial infiltration in MLNs and colon tissues. Additionally, GQD significantly increased the number of colonic goblet cells, repaired the structure of epithelial tight junctions and increased the expression of tight junction proteins. Furthermore, GQD significantly increased the proportion of IL-22 + ILC3 in the lamina propria, the expression of CYP1A1 protein in colon tissue, and the level of IL-22 in colon homogenates. However, the above protective effects of GQD were inhibited by co-administration of GQD and aryl hydrocarbon receptor (AhR) antagonist. Additionally, GQD restored the content of indole derivatives generated by tryptophan metabolism, regulated the diversity of the gut microbiota, and significantly increased the abundance of genes related to tryptophan metabolism., Conclusion: Our results confirmed that GQD repaired the damaged intestinal barrier in UC mice by regulating gut microbiota-related tryptophan metabolism and restoring the generation of indole derivatives to activate AhR-mediated IL-22 production., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Remimazolam is a novel ultrashort-acting intravenous benzodiazepine sedative−hypnotic that significantly reduces the times to sedation onset and recovery. This trial was conducted to confirm the recovery time from anesthesia of remimazolam-flumazenil versus propofol in patients undergoing endotracheal surgery under rigid bronchoscopy. Methods: Patients undergoing endotracheal tumor resection or stent implantation were randomly allocated into a remimazolam group (Group R) or a propofol group (Group P). The primary outcome was the recovery time from general anesthesia. The secondary outcomes were the time to loss of consciousness (LoC), hemodynamic fluctuations, and adverse events. Results: A total of 34 patients were screened, and 30 patients were enrolled in the study. The recovery time was significantly shorter for Group R (140 ± 52 s) than for Group P (374 ± 195 s) (p < 0.001). The times to LoC were 76 ± 40 s in Group R and 75 ± 25 s in Group P and were not significantly different. There were also no significant differences in hemodynamic fluctuations or adverse events between the two groups. Conclusions: The recovery time from general anesthesia in rigid bronchoscopy patients was shorter using remimazolam-flumazenil than with propofol, with no dramatic hemodynamic fluctuations and adverse events or differences between the agents. Remimazolam-flumazenil allows for faster recovery from anesthesia than propofol.

Equipment in a long-term marine atmosphere environment is prone to corrosion failure. Natural field exposure tests usually require a long time to obtain corrosion information. This study worked out a laboratory-accelerated corrosion test method that has a strong correlation with the natural environment test in Wanning, Hainan, and can be used as the basis for life assessment and the prediction of two high-strength stainless-steel materials. The mathematical model of corrosion weight loss of two high-strength stainless steels (3Cr13 and 00Cr12Ni10MoTi) was established by a field exposure test and a laboratory-accelerated corrosion test. Then, the correlation between the field exposure test and the laboratory-accelerated corrosion test was evaluated using qualitative and quantitative methods, and the acceleration ratio was calculated using the accelerated switching factor (ASF) method. The results show that: (1) The corrosion morphology of the two stainless steels after 15 days of laboratory-accelerated corrosion testing is similar to that obtained after two years of field exposure. (2) The value of gray correlation between the laboratory-accelerated corrosion test and the field exposure test is not less than 0.75. (3) The acceleration ratio of both stainless steels increases with the corrosion test time in the laboratory. The corrosion prediction models for the two stainless steels are T 3Cr13 = 6.234 t 1.634 and T 00Cr12Ni10MoTi = 55.693 t 1.322 , respectively.

Ethnopharmacological Relevance: Dahuang Mudan decoction (DMD) is a classic prescription for treating intestinal carbuncle from Zhang Zhongjing's "Essentials of the Golden Chamber" in the Han Dynasty. Recent studies also prove that DMD has a therapeutic effect on ulcerative colitis (UC), but its mechanism is still unclear., Aim of Study: In this study, we aim to assess the therapeutic effect of DMD on DSS-induced chronic colitis in mice and deeply expound its underlying regulative mechanism., Materials and Methods: The efficacy of DMD on mice with 2% DSS-induced chronic colitis was examined by changes in mouse body weight, DAI score, colon length changes, peripheral blood white blood cells (WBC) and red blood cells (RBC) counts, and hemoglobin (HGB) content, using mesalazine as a positive control. A small animal imaging system observed the FITC-Dextran fluorescence distribution in mice, and the contents of IL-22 and IL-17A in colon tissue homogenate supernatant and LPS in peripheral blood were detected by ELISA. Fluorescence in situ molecular hybridization and bacterial culture were used to investigate bacterial infiltration in intestinal mucosa and bacterial translocation in mesenteric lymph nodes and spleen. Mice immune function was further evaluated by analyzing the changes in spleen index, thymus index, and the ratio of peripheral blood granulocytes, monocytes, and lymphocytes. Meanwhile, the proportion of NCR + group 3 innate lymphoid cells (ILC3), NCR - ILC3, and IL-22 + ILC3 in colonic lamina propria lymphocytes of mice was detected by flow cytometry. The contents of effectors IL-22, IL-17A, and GM-CSF were detected by RT-PCR. We use cell scratching to determine the effect of DMD conditioned medium on the migration of Caco-2 cells by establishing an in vitro model of MNK-3 conditioned medium (CM) intervening Caco-2 cells. RT-PCR and WB detect the expression of tight junction ZO-1, Occludin, and Claudin-1., Results: DMD restored the body weight, colon length, peripheral blood RBC numbers, and HGB content of chronic colitis mice and reduced peripheral blood WBC and colon inflammatory cell infiltration. Moreover, DMD decreased LPS content in serum, bacterial infiltration of colonic mucosa, and bacterial translocation in spleen and mesenteric lymph nodes. Simultaneously, DMD intensified the expression of ZO-1, Occludin, and Claudin-1, the ratio of NCR + ILC3 and IL-22 + ILC3, and decreased the proportion of NCR - ILC3. In vitro studies also confirmed that the conditioned medium of DMD promoted the migration of Caco-2 cells and the expression of tight junction proteins., Conclusion: Our results confirm that DMD improves inflammation and restores intestinal epithelial function in mice with chronic colitis, and the mechanism may be related to regulating ILC3 function., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Colorectal cancer is associated with ulcerative colitis (UC). The infiltration of neutrophils is the main cause of DNA damage produced by inflammation in the intestinal epithelium. Under the action of peptidyl arginine deaminase 4 (PAD4), neutrophils dissociate chromatin and form neutrophil extracellular traps (NETs), which can aggravate tissue inflammation and encourage tumor development. Although Huang Qin Decoction (HQD) was found to be useful in treating UC and was used to gradually prevent and treat digestive tract cancers, the underlying reasons were unclear., Methods: To demonstrate HQD could inhibits the initiation of colitis associated carcinogenesis by controlling NETs related inflammation, we first performed an AOM/DSS-generated colitis-associated carcinogenesis model to assess the efficacy of HQD in reducing neutrophil infiltration and anti-tumor activity. Then, using network pharmacology research, we investigated the potential mechanisms underlying those medicinal effects, as demonstrated by the detection of NETs aggregation and PAD4 expression changes in the colon., Results: HQD substantially reduced the number of colon cancers and the expression of Ki67, restored the level of intestinal tight junction protein occludin and ZO-1, and relieved the intestinal inflammation caused by TNF-α, IL-1β. At the same time, it inhibited neutrophil infiltration in the colon and improved the immunosurveillance of CD8 + T cells. The potential mechanisms of HQD intervention against UC and UC with neoplasia (UCN) were studied using network pharmacology, and 156 conjunct genes as well as numerous inflammation-related pathways were identified. Protein-protein interaction (PPI) analysis indicated that HQD inhibition of intestinal tumors might be related to the deactivation of PAD4, which was verified by the down-regulation of NETs, MPO-DNA complex levels, and PAD4 expression after HQD treatment., Conclusion: Huang Qin Decoction inhibits the initiation of colitis associated carcinogenesis by controlling PAD4-dependent neutrophil extracellular traps., Competing Interests: Declaration of Competing Interest The authors declared that they had no conflicts of interest to disclose., (Copyright © 2022. Published by Elsevier GmbH.)

Ulcerative colitis (UC) is a multifactorial, refractory chronic inflammatory disease. The primary factor leading to prolonged ulcerative colitis is the imbalance of the group 3 innate lymphoid cells (ILC3) subgroup resulting in the delayed reconstruction of damaged intestinal barrier. Previous studies show that luteolin had efficacy on UC, however, the potency of luteolin on restoring the balance of NCR - ILC3/NCR + ILC3 to repairing impaired intestinal barrier remains unclear. In this study, to investigate the potential mechanism of luteolin on ILC3 subgroup, we first evidenced that luteolin could promote transformation NCR - MNK3 to NCR + MNK3 in vitro. Then, a UC model was established in C57BL/6J mice to assess the efficacy of luteolin in restoring ILC3 subgroup balance and repairing intestinal barrier in chronic UC. Finally, the experiments in vitro validated the potential mechanism of luteolin in regulating ILC3 plasticity. The results showed that luteolin significantly alleviated the symptoms of DSS-induced UC in mice, including preventing body weight loss and decreasing the disease activity index (DAI) and intestinal damages. Additionally, luteolin increased NCR + ILC3 levels, promoted the production of IL-22 and decreased the levels of IL-17a and INF-γ in the intestine, and encourage intestinal barrier function recovery in UC mice by promoting the expression of ZO-1 and Occludin. Experiments in vitro revealed that luteolin facilitated the transformation of NCR - MNK3 to NCR + MNK3 and promoted the secretion of IL-22, which was linked to the Notch pathway. All results revealed that luteolin restored the balance of NCR - ILC3/NCR + ILC3 and contributed to repair of injured intestinal epithelium to alleviate ulcerative colitis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: The prognosis and efficacy of laparoscopic surgery (LPS) and open surgery or robotic surgery (RS) on endometrial carcinoma (EC) patients were compared., Methods: Data as of May 2021 were retrieved from databases like PubMed, Embase, Cochrane Library, and Web of Science. The study involved randomized controlled trials (RCTs), cohort studies, or case-control studies for comparing the effects of LPS and open surgery or robotic surgery (RS) on EC treatment. The primary outcomes included duration of operation, blood loss, length of stay (LOS), postoperative complications, and recurrence rate. Secondary outcomes included 3-year progression-free survival (PFS) rate/disease-free survival (DFS) rate and 3-year overall survival (OS) rate., Results: A total of 24 studies were involved, and all of them were cohort studies except 1 RCT and 1 case-control study. There was no significant difference in duration of operation between LPS and open surgery (MD = -0.06, 95% CI: -0.37 to 0.25) or RS (MD = -0.15, 95% CI: -1.27 to 0.96). In comparison with the open surgery, LPS remarkably reduced blood loss (MD = -0.43, 95% CI: -0.58 to -0.29), LOS (MD = -0.71, 95% CI: -0.92 to -0.50), and the complication occurrence rate (RR = 0.83, 95% CI: 0.73 to 0.95). However, LPS and RS saw no difference in blood loss (MD = 0.01, 95% CI: -0.77 to 0.79). Besides, in comparison with RS, LPS prominently shortened the LOS (MD = 0.26, 95% CI: 0.12 to 0.40) but increased the complication occurrence rate (RR = 1.74, 95% CI: 1.57 to 1.92). In contrast to open surgery or RS, LPS saw no difference in occurrence rate (RR = 0.75, 95% CI: 0.56 to 1.01; RR = 0.97, 95% CI: 0.62 to 1.53), 3-year PFS/DFS (RR = 0.99, 95% CI: 0.90 to 1.09; RR = 1.30, 95% CI: 0.87 to 1.96), and 3-year OS (RR = 0.97, 95% CI: 0.91 to 1.04; RR = 1.21, 95% CI: 0.91 to 1.60)., Conclusion: In sum, LPS was better than open surgery, which manifested in the aspects of less blood loss, shorter LOS, and fewer complications. LPS, therefore, was the most suitable option for EC patients. Nevertheless, LPS had no advantage over RS, and sufficient prospective RCTs are needed to further confirm its strengths., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Jiong Ma et al.)

This study tracked and recorded the weight changes of 13 captive Sunda pangolin cubs from lactation to maturity to explored the appropriate weaning time and reveal the rules of its weight growth. SPSS 25.0 was used to build a cubic equation model to fit the body weight change rules of 4 individuals who nonvoluntarily ingested artificial feed (NIAF) at 127 days after birth and 5 individuals who voluntarily ingested artificial feed (VIAF) at 86-108 days after birth. The body weight of NIAF cubs aged 0-120 days and VIAF cubs aged 0-150 days were estimated according to the fitting model. An independent sample T-test was performed on the mean body weight of the two groups during the late lactation period. The results showed that at 105 days after birth, the body weight of the VIAF group was significantly higher than that of the NIAF group (P = 0.049), and the body weight of the VIAF group was extremely significantly higher than that of the NIAF group at 114 days (P = 0.008); The peak cumulative body weight of the NIAF cubs during lactation appeared around 130 days of age (n = 3); The mortality rate was 66.7% (n = 3) after about 150 days if the feed was continuously consumed nonvoluntarily. It was concluded that the milk secretion period of the mother is about 0-5 months after giving birth; the weaning period of the cubs should be 4-5 months after birth. If the cubs don't follow the mother to eat artificial feed for 3 months after birth, it can start be induced with artificial diet which adds termites, and the time point cannot be later than 130 days, otherwise it is not conducive to the survival of the cubs; When sexually mature, the body length and body weight of female cubs account for about 84% and 60% of the adult, respectively; the body maturity and body weight of female cubs tend to be stable about 15.3 months and 16.4 months, respectively. Finally, a special needle-shaped nipples and nursing patterns of female Sunda pangolins were also recorded in this study. These findings play an important role in guiding the nursing of captive Sunda pangolin cubs and other pangolin cubs. It is expected to improve the survival rate of the cubs by exploring the appropriate weaning time and the rules of weight growth. By scientifically planning the reproductive cycle of the female Sunda pangolins, our goal is to expand the population size and eventually release to the wild, meanwhile improving knowledge of this critically endangered species., Competing Interests: The authors have declared that no competing interests exist.

The first de novo synthesis of 1-hydroxyl allogibberic methyl ester, en route to pharbinilic acid and other bioactive molecules, is accomplished in diastereoselective manner. Key reactions of the synthesis include a Pd-catalyzed Suzuki-Miyaura cross-coupling reaction, a Lewis acid-catalyzed reductive Prins cyclization reaction, and a SmI 2 -mediated transannular pinacol coupling reaction. The synthesis provides a new avenue to access diverse relevant bioactive molecules.

Images taken by an endoscope in single-port-access surgery are the most important information for directing surgeons to operate, so acquiring images taken at better position and a more desired perspective has profound significance for improving the efficiency and safety of surgery. The magnetically anchored laparoscope can help to realize this goal compared with the traditional laparoscope used in single-port-access surgery. In this paper, we propose the concept of applying ultrasonic motors in the magnetically anchored laparoscope. Two types of ultrasonic motors used for driving the laparoscope, namely a miniature traveling wave-rotating ultrasonic motor and a miniature traveling wave-tilt ultrasonic motor, are designed. The prototype of the magnetically anchored laparoscope using these two types of ultrasonic motors is fabricated and evaluated by experiments. The results show that the maximum output torque of the miniature traveling wave-rotating ultrasonic motor is 1.2 mN·m, and that of the miniature traveling wave-tilt ultrasonic motor is 1.4 mN·m, which is enough to actuate the magnetically anchored laparoscope. Additionally, it is proven that the two designed ultrasonic motors can be applied successfully in the laparoscope.

Synthesizing many-body interaction Hamiltonians is a central task in quantum simulation. However, it is challenging to synthesize Hamiltonians that have more than two spins in a single term. Here we synthesize m-body spin-exchange Hamiltonians with m up to 5 in a superconducting quantum circuit by simultaneously exciting multiple independent qubits with time-energy correlated photons generated from a qudit. The dynamic evolution of the m-body interaction is governed by the Rabi oscillation between two m-spin states, in which the states of each spin are different. We demonstrate the scalability of our approach by comparing the influence of noises on the three-, four- and five-body interaction and building a many-body Mach-Zehnder interferometer which potentially has a Heisenberg-limit sensitivity. This study paves a way for quantum simulation involving many-body interaction Hamiltonians such as lattice gauge theories in quantum circuits.

Purpose: Esophageal squamous cell carcinoma (ESCC) is one of the most common and serious malignancies in China. However, the exact mechanisms of tumor progression are still unclear. Thus, identifying biomarkers for early diagnosis, prognostic and recurrence assessment of ESCC is necessary., Experimental Design: iTRAQ was used to identify differentially expressed proteins (DEPs) in tumor tissues. N-alpha-acetyltransferase 10 (NAA10) is confirmed and validated by immunohistochemistry and western blotting. Furthermore, the effects of NAA10 on TE-1 cells were detected by CCK-8, colonies formation, anchorage-independent growth in soft agar, migration and transwell assays. LinkedOmics was used to identify differential gene expression with NAA10 and to analyze Gene Ontology and KEGG pathways. Coexpression gene network was conducted by the STRING database and Cytoscape software (MCODE plug-in)., Results: 516 DEPs were identified. NAA10 was downregulated in cancer tissues and selected for further confirmed. Furthermore, NAA10 can inhibit proliferation and tumorigenesis, and suppress migration and invasion of TE-1. Functional network analysis suggested that NAA10 regulates the ribosome pathways involving eight ribosomal proteins., Conclusion and Clinical Relevance: These findings clearly demonstrated that NAA10 is a tumor suppressor and novel potential biomarker for ESCC, laying a foundation for further study of the role of NAA10 in carcinogenesis., (© 2022 Wiley-VCH GmbH.)

Colorectal cancer is a serious threat to human health. Colonoscopy is the most effective procedure for the inspection of colorectal cancer. However, traditional colonoscopy may cause pain, which can lead to the patient's fear of colonoscopy. The use of active-motion colonoscopy robots is expected to replace traditional colonoscopy procedures for colorectal cancer screening, without causing pain to patients. This paper proposes an inchworm-like soft colonoscopy robot based on a rubber spring. The motion mechanism of the robot consists of two anchoring units and an elongation unit. The elongation unit of the robot is driven by 3 cables during contraction and by its inherent elasticity during extension. The balloon is selected as the anchoring mechanism of the robot. It has soft contact with the colon and will not damage the colon wall, which means no discomfort is caused. The elastic force test of the rubber spring shows that the elongation unit of the robot has sufficient restorative force to drive the robot to move forward and backward. The influence of the balloon's expansion size on the dexterity of the robot head is analyzed, and the functions of the balloons are expounded. The balloon can not only assist the robot in its locomotion but also assist the robot to perform a better inspection. The robot can move successfully in a horizontal, straight, and inclined isolated pig colon, showing great clinical application potential.

Acoustic black holes offer superior capabilities for slowing down and trapping acoustic waves for various applications such as metastructures, energy harvesting, and vibration and noise control. However, no studies have considered the linear and nonlinear effects of acoustic black holes on micro/nanoparticles in fluids. This study presents acoustofluidic black holes (AFBHs) that leverage controlled interactions between AFBH-trapped acoustic wave energy and particles in droplets to enable versatile particle manipulation functionalities, such as translation, concentration, and patterning of particles. We investigated the AFBH-enabled wave energy trapping and wavelength shrinking effects, as well as the trapped wave energy-induced acoustic radiation forces on particles and acoustic streaming in droplets. This study not only fills the gap between the emerging fields of acoustofluidics and acoustic black holes but also leads to a class of AFBH-based in-droplet particle manipulation toolsets with great potential for many applications, such as biosensing, point-of-care testing, and drug screening.

Background: To develop and evaluate the prognostic value of a comprehensive inflammatory biomarker for postoperative colorectal cancer (CRC) patients., Methods: A total of 646 CRC patients were recruited between August 2017 and December 2019 from Fujian Medical University Union Hospital, with follow-up data up to 2021. The least absolute shrinkage and selection operator method (LASSO) was used to select inflammation indicators in order to construct a comprehensive biomarker (named NSAP). The Cox regression model was utilized to analyze the association between the NSAP and the disease-free survival (DFS) of CRC. Predictive performance and clinical utility of prognostic models were evaluated by area under the curve (AUC) and decision curve analyses (DCAs)., Results: During a median follow-up of 23 months, 95 clinical outcomes were observed, with a 1-year survival rate is 89.47%. A comprehensive inflammatory biomarker (NSAP) was established based on four blood indicators (including neutrophil-to-lymphocyte ratio (NLR), neutrophil×monocyte-to-lymphocyte ratio (SIRI), albumin-to-globulin ratio (AGR), and platelet-to-lymphocytes ratio (PLR)). Patients with a lower NSAP had significantly associated with better DFS of CRC (HR=0.53, 95%CI 0.32-0.89). Moreover, compared to a previously established model, the traditional TNM staging system or/and tumor markers, the nomogram based on NSAP displayed more excellent predictive ability (0.752 vs 0.597, 0.711 and 0.735, P < 0.05). DCAs also demonstrated that the established nomogram had better utility for decision making., Conclusions: Our study suggests that NSAP may be a useful comprehensive prognostic biomarker for predicting the DFS of CRC patients. The nomogram based on NSAP can be considered a valuable tool to estimate the prognosis of patients with CRC., (© 2022. The Author(s).)

A direct 1,2-dibromination method of alkenes is realized using 1,3-dibromo-5,5-dimethylhydantoin (DBDMH) as a bromine source. This reaction proceeds under mild reaction conditions without the use of a catalyst and an external oxidant. Various sorts of alkene substrates are transformed into the corresponding 1,2-dibrominated products in good to excellent yields with broad substrate scope and exclusive diastereoselectivity. This method offers a green and practical approach to synthesize vicinal dibromide compounds.

As an irreplaceable element for obtaining airflow information in many engineering scenarios, airflow sensors have gained increasing attention across the fields of aerospace engineering, environmental engineering, sustainable energy exploitation, meteorology research, and so on. As one of the mainstream airflow sensing principles, piezoresistive airflow velocity sensors have experienced rapid growth over the years, while effective vector airflow sensors with the ability of detecting both airflow velocity and direction based on the piezoresistive principle are scarce. Here, on the basis of our developed piezoresistive airflow velocity sensors based on pressure loading mode, we design an array of these sensors and propose a corresponding explicit algorithm for simultaneous detection of airflow velocity and direction. This sensor array configuration enables an automatic recognition function of the quadrant of incoming airflow, which can significantly simplify the reverse calculation of airflow information compared with conventional vector airflow sensors. The experimental results demonstrate the decent performance of this sensor array for identifying both airflow velocity and direction. This study not only fills the gap between our developed airflow velocity sensor and the ability of detecting airflow direction but also presents a simple and universal array-based strategy for vector airflow sensing, which could be widely applied in airflow sensors based on other principles.

Hexavalent chromium (Cr(VI)) is considered to be a potential metal contaminant because of its toxicity and carcinogenicity. In this work, the surface charge density of nickel-iron layered double hydroxide (NiFe LDH) is tuned through iron valence change to improve the performance in adsorption of Cr(VI). The addition of iron divalent in the precursor enhances the surface positivity and reducibility of Fe 2+ -NiFe LDH, resulting in a nearly 150% Cr(VI) maximum adsorption capacity improvement. The increase of hydroxyl groups and charge density on the surface of NiFe LDH is due to the topological chemical transition from Ni 2+ -Fe 2+ LDH to Ni 2+ -Fe 3+ LDH. The adsorption of Cr(VI) onto Fe 2+ -NiFe LDH prepared via topochemical approach is highly pH-dependent. The adsorption dynamics and isotherms results may be clearly elucidated by the pseudo-second-order model and Langmuir isotherm model. Electrostatic attraction, interlayer anion exchange and adsorption-coupled reduction are proven to be the main Cr(VI) removal mechanisms for Fe 2+ -NiFe LDH. This finding demonstrates that Fe 2+ -NiFe LDH adsorbents have potential application for efficient removal of Cr(VI) pollutants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Esophageal squamous cell carcinoma (ESCC) is a predominant subtype of esophageal cancer (EC) and has a poor prognosis due to its aggressive nature. Accordingly, it is necessary to find novel prognostic biomarkers and therapeutic targets for ESCC. Lysine-specific histone demethylase 1 (LSD1) plays a core role in the regulation of ESCC oncogenesis. However, the detailed mechanism of LSD1-regulated ESCC growth has not been elucidated. This study aims to explore molecular mechanism underlying the LSD1-regulated ESCC's oncogenesis. After LSD1 silencing, we detected differentially expressed genes (DEGs) in human ESCC cell line, TE-1, by transcriptome sequencing. Subsequently, we investigated expression pattern of the selected molecules in the ESCC tissues and cell lines by qRT-PCR and Western blotting. Furthermore, we explored the roles of selected molecules in ESCC using gene silencing and overexpression assays. Transcriptome sequencing showed that the expression of dual specificity phosphatase 4 (DUSP4) in TE-1 was significantly attenuated after the LSD1 silencing. In addition, the DUSP4 mRNA expression level was significantly higher in the ESCC tissues, especially in those derived from patients with invasion or metastasis. Moreover, the DUSP4 expression was positively associated with the LSD1 expression in the ESCC tissues. DUSP4 overexpression promoted proliferation, invasion, and migration of the ESCC cells, while DUSP4 silencing had an opposite effect. DUSP4 overexpression also enhanced tumorigenicity of the ESCC cells in vivo, while DUSP4 silencing inhibited tumor growth. Importantly, inhibition of cell proliferation, invasion, and migration by the LSD1 inhibitor (ZY0511) was reversed by DUSP4 overexpression. Conclusively, we found that LSD1 promotes ESCC's oncogenesis by upregulating DUSP4, the potential therapeutic and diagnostic target in ESCC.

The treatment of combination drugs in complex diseases has been spotlighted. Ulcerative colitis (UC) is a chronic inflammatory disease that has made progress in combination therapy. Baicalin, a flavone from Scutellaria baicalensis Georgi. (Lamiaceae), and emodin, an anthraquinone derivative from Rhei Radix et Rhizoma. (Polygonaceae), both have been reported to possess antiinflammatory activities. Our study investigated whether combined treatment with baicalin and emodin had a synergistic effect in inhibiting colitis inflammation. The results showed that baicalin combined with emodin at a lower dose had the same effect as the two drugs alone significantly alleviated the symptoms of dextran sulfate sodium (DSS)-induced colitis mice, involving the prevention of the loss of body weight and colon shortening, the decrease in the disease activity index (DAI), and intestinal damages. The combined treatment decreased the expression of CD14/TLR4/NF-κB pathway proteins and increased the expression of PPAR-γ protein in the colon of colitis mice. Further study in vitro has shown that baicalin decreased the expression of CD14, whereas emodin increased the expression of PPAR-γ, both of which inhibited the activity of NF-κB and exerted antiinflammatory effects. Furthermore, compared to the treatment using the two drugs individually, baicalin combined with emodin had more significant effects on the expression of CD14 and PPAR-γ. Therefore, emodin combined with baicalin had a synergistic effect on DSS-induced colitis., (© 2021 John Wiley & Sons Ltd.)