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Chitosan (Ch) is one of the most commonly used natural biomaterials. Osteodifferentiation of mesenchymal stem cells (MSCs) on Ch has drawn extensive interest. Hydroxyapatite (HA) is a component of skeleton and teeth with good biocompatibility. Combination with HA may be a good method to modify Ch to facilitate cellular behaviors and functions on it. In this study, Ch/HA film was prepared and characterized. Its potential to benefit cellular behaviors and osteodifferentiation of MSCs was evaluated. Resultantly, physical properties of composite Ch/HA, including water-in-air contact angle, tensile strength, elastic modulus, and breaking elongation were favorably modified. In cellular culture medium, Ch/HA films absorbed more Ca2+ than Ch films, and more HA crystalline growths on Ch/HA films. 3-(4,5-Dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and morphological features showed better proliferation and adhesion of MSCs on Ch/HA films. Osteodifferentiation of MSCs on Ch/HA was promoted, indicated by modified transcription level of osteocalcin, osteopontin, collagen I, alkaline phosphatase (ALP), and induced ALP activity. These data suggest biocompatibility of Ch is modified after being blended with HA, which promotes osteodifferentiation of MSCs. This can be a promising approach to modify Ch for its applications in bone tissue engineering. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 1202-1209, 2014. [ABSTRACT FROM AUTHOR]

The recombinant adeno-associated virus 8 (rAAV8) vector is a widely used tool in basic research and clinical trials. The cytomegalovirus immediate-early enhancer/chicken β-actin (CAG) promoter is a synthetic promoter used in adenoviral constructs with a wide spectrum and notable efficiency. The thyroxine binding globulin (TBG) promoter is a liver-specific promoter, which directs transgene expression in hepatocytes. However, the transduction efficiency of the rAAV vector is dependent on both the administration routes and the promoter elements. In the present study, the transduction efficiency in the liver following intraperitoneal (IP) and intravenous (IV) injections of rAAV8 with the CAG, TBG669 and TBG410 promoters was compared. Enhanced green fluorescent protein (EGFP) expression was used as the biomarker to indicate efficiency. Among the three different promoters, CAG exhibited the highest efficiency from both IV and IP injections. Following IV administration, EGFP expression, induced by the CAG promoter, was 67-fold higher compared with that in the TBG410 promoter group and 26-fold higher compared with that in the TBG669 promoter group. EGFP protein expression was higher with IV injection compared with that for IP injection for both the CAG and TBG669 promoters (P<0.05). With the CAG promoter, EGFP protein expression was 1.5-fold higher with the use of IV injection than with IP injection. With the TBG410 promoter, no differences were observed between the two administrations. In conclusion, these findings demonstrated that the CAG promoter was much more efficient at driving gene expression in the liver compared with that for the TBG promoters in rAAV8. In addition, IP administration produced comparable efficiency for gene delivery via the rAAV8 vector, particularly with the promoter TBG410. [ABSTRACT FROM AUTHOR]

• To enhance the immersive operating experience by reducing time delays, a control system based on OROCOS and DDS has been presented to rapidly establish the bilateral teleoperation system with real-time performance. • A bilateral control algorithm combining closed-loop pose tracking and force feedback is proposed to improve the pose tracking accuracy of the slave robot and enhance the sense of telepresence. • A lightweight experimental setup has been constructed based on the maintenance scenario in EAST. Relative experiments have been conducted to validate the accuracy and effectiveness of the bilateral teleoperation system. Bilateral teleoperation is a control strategy used in remote handling (RH) to enable an operator to control a robot or system while perceiving the interactive force in the environment. To enhance the immersive operating experience by reducing time delays, a control system based on OROCOS and DDS has been presented to rapidly establish the bilateral teleoperation system with real-time performance. Additionally, a bilateral control algorithm combining closed-loop pose tracking and force feedback is proposed to improve the pose tracking accuracy of the slave robot and enhance the sense of telepresence. As a part of the pre-study on the tile assembly conducted by CMOR in Chinese Fusion Engineering Test Reactor (CFETR), a lightweight experimental setup has been constructed based on the maintenance scenario in EAST. Relative experiments have been conducted to validate the accuracy and effectiveness of the bilateral teleoperation system. The results demonstrate low latency and smooth control during the bilateral teleoperation process. [ABSTRACT FROM AUTHOR]

EAST Optical Diagnostic Beam Orientation Robot (EODBOR) is designed for the calibration of the visible optical diagnostic system before the plasma experiment, which can orientate light beams with high precision. At present, the motion of EODBOR is purely controlled by the operators during the whole calibration process since planning algorithms based on prior knowledge of the environment cannot be adopted due to the intrinsically unstructured property of EAST's vacuum vessel. To automate the calibration, we upgraded our previous system and propose a method for environment-aware motion planning based on Robot Operating System (ROS). In this method, the probabilistic octree is used to represent unknown objects in the environment, which is updated with point clouds from an RGB-D camera mounted at the end of the manipulator. We verify the feasibility and stability of the proposed method through simulations and experiments. • An environment-aware motion planning system based on Robot Operating System (ROS) is developed. • A hand–eye calibration method for RGB-D cameras using a calibration sphere is proposed. • Simulations are carried out in a virtual scene based on the real size of the vacuum vessel of EAST and the installation position of the robotic arm. • Experiments using an eye-in-hand system consisting of a UR5 robotic arm and a RealSense D435 validate the feasibility of the proposed method. [ABSTRACT FROM AUTHOR]

• A modified RepVGG based visual servo method for quick-change tool alignment is investigated. • The robot is controlled by the position-based visual servo control law. • Experiments in real world are conducted to validate the effectiveness of the proposed visual servo method. The remote maintenance process for fusion reactor is complex, which can be very time-consuming and labor-consuming. This paper proposes a modified neural network based visual servo method to align a quick-change device with robot camera system. A classical position-based visual servo control law is used to guide the robot to reach the desired position. The key target for the above visual servo controller is to obtain a robust pose estimator to calculate the quick-change device pose with respect to the camera. This pose estimator is trained using RepVGG model with a self built image samples. An attention mechanism is added to the neural network to enhance the stability of pose prediction for reflective metal objects. The robot joint speed is also smoothed to reduce the image motion blur effect and make the visual servo process stable. The performance of the proposed visual servo controller was verified on an UR5 robot, and the results show that the stable and rough alignment of the quick-change device can be realized. [ABSTRACT FROM AUTHOR]

• This multi-center RCT will provide evidence for the rational application of PPI in ESD. • Low-dose PPIs were sufficient for prevention post-ESD bleeding and its efficacy level was equivalent to high dose PPIs. • Artificial ulcer healing after ESD in low-dose PPIs was similar to high dose PPIs. Although proton pump inhibitors (PPIs) are widely used in the prevention of gastric bleeding caused by endoscopic submucosal dissection (ESD), there is no consensus on the optimal regimen for these patients. Therefore, we aim to investigate whether intermittent use of low-dose PPI is sufficient to prevent post-ESD bleeding. This multicenter, non-inferiority, randomized controlled trial was conducted at 9 hospitals in China. Consecutive eligible patients with a diagnosis of gastric mucosal lesions after ESD treatment were randomly assigned (1:1) to receive either intermittent low-dose or continuous high-dose PPIs treatment. After three days, all patients administered orally esomeprazole 40 mg once a day for 8 weeks. The primary endpoint was post-ESD bleeding within 7 days. Analysis was done according to the intention-to-treat principle with the non-inferiority margin (Δ) of 5%. 526 consecutive patients were assessed for eligibility from 30 September 2017 to 30 July 2019, of whom 414 were randomly assigned to low-dose (n = 209) or high-dose (n = 205) esomeprazole treatment group without dropouts within7 days. The total post-ESD bleeding is occurred in 13 (6.2 %, 95 % CI 3.3–9.6) of 209 within 7 days in the intermittent low-dose group, and 12 (5.9 %, 95 % CI 2.9–9.3) of 205 in the continuous high-dose group. The absolute risk reduction (ARR) was 0.4 % (−4.2, 4.9). One month after ESD, There are 44 patients (21.1 %, 95 % CI 15.8, 26.8) and 39 patients (19.0 % 95 % CI 13.7, 24.4) in scar stage respectively in low-dose group and high-dose group (P = 0.875).The hospital costs in the low-dose PPI group was lower than high -dose group (P = 0.005). The intermittent use of low-dose PPIs is sufficient to prevent post-ESD bleeding. It might be applied in clinical practice to prevent post-ESD bleeding and reduce the costs related to PPIs. [ABSTRACT FROM AUTHOR]

Nitryl chloride (ClNO 2 ) is a key precursor of chlorine radicals, influencing atmospheric oxidation and secondary pollutants formation. Few studies have examined the ClNO 2 chemistry from the perspective of the planetary boundary layer. Here, we conducted a vertically resolved investigation of ClNO 2 at six heights (ranging from 5 to 335 m) on a 356 m tower in the Pearl River Delta, China, during winter 2021. Nocturnal ClNO 2 is notably lower at the surface than the upper layers, with the nocturnal median concentration at 220 m (51 parts per trillion by volume, pptv) being approximately three times higher than that recorded in the surface layer (16 pptv). Observation-constrained box model simulations show that the NO gradients primarily account for the vertical disparities. Compared to the hydroxyl radical (OH) production via the nitrous acid and ozone photolysis, ClNO 2 photolysis contributes to radical formation by 3.8% (1.8%) at 220 m (5 m) in the morning (07:00-08:00), indicates the enhanced significance of ClNO 2 chemistry aloft compared with the ground, and may cause the underestimation of ClNO 2 photolysis impacts if solely relying on surface measurements. We highlight that more field studies are needed to elucidate ClNO 2 chemistry across the boundary layer.

Background/aims: Dexamethasone (DEX) is a widely used exogenous therapeutic glucocorticoid in clinical settings. Its long-term use leads to many side effects. However, its effect on metabolic disorders in individuals on a high-fat diet (HFD) remains poorly understood., Methods: In this study, HFD-fed mice were intraperitoneally injected with DEX 2.5 mg/kg/day for 30 days. Lipid metabolism, adipocyte proliferation, and inflammation were assayed using typical approaches., Results: DEX increased the epididymal fat index and epididymal adipocyte size in HFD-fed mice. The number of epididymal adipocytes with diameters > 70 μm accounted for 0.5% of the cells in the control group, 30% of the cells in the DEX group, 19% of the cells in the HFD group, and 38% of all the cells in the D+H group. Adipocyte proliferation in the D+H group was inhibited by DEX treatment. Adipocyte enlargement in the D+H group was associated with increased the lipid accumulation but not the adipocyte proliferation. In contrast, the liver triglyceride and total cholesterol levels and their metabolism were downregulated by the same treatment, indicating the therapeutic potential of DEX for nonalcoholic fatty liver disease., Conclusion: DEX synergizes with HFD to promote lipid deposition in adipose tissues. A high risk of obesity development in patients receiving HFD and DEX treatment is suggested.

Pancreatic β-cell dysfunction caused by obesity can be associated with alterations in the levels of miRNAs. However, the role of miRNAs in such processes remains elusive. Here, we show that pancreatic islet miR-27a-5p, which is markedly increased in obese mice and impairs insulin secretion, is mainly delivered by visceral adipocyte-derived extracellular vesicles (EVs). Depleting miR-27a-5p significantly improved insulin secretion and glucose intolerance in db/db mice. Supporting the function of EV miR-27a-5p as a key pathogenic factor, intravenous injection of miR-27a-5p-containing EVs showed their distribution in mouse pancreatic islets. Tracing the injected adeno-associated virus (AAV)-miR-27a-5p (AAV-miR-27a) or AAV-FABP4-miR-27a-5p (AAV-FABP4-miR-27a) in visceral fat resulted in upregulating miR-27a-5p in EVs and serum and elicited mouse pancreatic β-cell dysfunction. Mechanistically, miR-27a-5p directly targeted L-type Ca2+ channel subtype CaV1.2 (Cacna1c) and reduced insulin secretion in β-cells. Overexpressing mouse CaV1.2 largely abolished the insulin secretion injury induced by miR-27a-5p. These findings reveal a causative role of EV miR-27a-5p in visceral adipocyte-mediated pancreatic β-cell dysfunction in obesity-associated type 2 diabetes mellitus., (© 2024 by the American Diabetes Association.)

Nitrogen oxides (NO x ) are crucial in tropospheric photochemical ozone (O 3 ) production and oxidation capacity. Currently, the widely used NO x measurement technique is chemiluminescence (CL) (CL-NO x ), which tends to overestimate NO 2 due to atmospheric oxidation products of NO x (i.e., NO z ). We developed and characterized a NO x measurement system using the cavity attenuated phase shift (CAPS) technique (CAPS-NO x ), which is free from interferences with nitrogen-containing species. The NO x measured by the CAPS-NO x and CL-NO x analyzers were compared. Results show that both analyzers showed consistent measurement results for NO, but the NO 2 measured by the CAPS-NO x analyzer (NO 2&#95;CAPS ) was mostly lower than that measured by the CL-NO x analyzer (NO 2&#95;CL ), which led to the deviations in O 3 formation sensitivity regime and O x (= O 3 + NO 2 ) sources (i.e., regional background and photochemically produced O x ) determined by the ozone production efficiencies (OPE) calculated from NO 2&#95;CL and NO 2&#95;CAPS . Overall, OPE &#95;CL exceeded OPE &#95;CAPS by 18.9%, which shifted 3 out of 13 observation days from the VOCs-limited to the transition regime when judging using OPE &#95;CL , as compared to calculations using OPE &#95;CAPS . During the observation period, days dominated by regional background O x accounted for 46% and 62% when determined using NO 2&#95;CL and NO 2&#95;CAPS , respectively. These findings suggest that the use of the CL-NO x analyzer tends to underestimate both the VOCs-limited regime and the regional background Ox dominated days. The newly built CAPS-NO x analyzer here can promote the accurate measurement of NO 2 , which is meaningful for diagnosing O 3 formation regimes and O x sources., 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. Published by Elsevier B.V.)

Casein (CN) is a common allergen that is challenging to avoid in modern foods. The effect of cold argon plasma (CAP) on reducing CN antigenicity was investigated, focusing on alterations in epitope structure and sequence. CAP mainly contains hydroxyl radicals (∙OH). After a 12-min CAP treatment, the result of ELISA demonstrated an 80.46 % reduction in antigenicity. Transmission electron microscopy and electrophoresis revealed that certain CN aggregated, while multispectral analysis indicated that part of CN was fragmented into smaller peptides. The predictive 3D model suggested the disruption of linear epitopes located in the α-helix region might contribute to the reduced allergenicity. The peptide sequences were compared to the linear epitopes predicted by immunoinformatics approaches, revealing some reduction or breakage of key allergic sequences. Meanwhile, amino acids with aromatic side chains and hydrophobic groups were susceptible to CAP-induced modifications. This investigation demonstrated CAP could be beneficial for processing hypoallergenic foods., 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.)

Aim: To assess the expression and function of miR-483-5p in diabetic β cells., Methods: The expression of miR-483-5p was evaluated in the pancreatic islets of obesity mouse models by quantitative reverse transcription polymerase chain reaction. Dual-luciferase activity, and western blotting assays, were utilized for miR-483-5p target gene verification. Mice with β cell-specific miR-483-5p downregulation were studied under metabolic stress (i.e. a high-fat diet) condition. Lineage tracing was used to determine β-cell fate., Results: miR-483-5p increased in the islets of obese mouse models. Expression levels of miR-483-5p were significantly upregulated with the treatment of high glucose and palmitate, in both MIN6 cells and mouse islets. Overexpression of miR-483-5p in β cells results in impaired insulin secretion and β-cell identity. Cell lineage-specific analyses revealed that miR-483-5p overexpression deactivated β-cell identity genes (insulin, Pdx1 and MafA) and derepressed β-cell dedifferentiation (Ngn3) genes. miR-483-5p downregulation in β cells of high-fat diet-fed mice alleviated diabetes and improved glucose intolerance by enhancing insulin secretory capacity. These detrimental effects of miR-483-5p relied on its seed sequence recognition and repressed expression of its target genes Pdx1 and MafA, two crucial markers of β-cell maturation., Conclusions: These findings indicate that the miR-483-5p-mediated reduction of mRNAs specifies β-cell identity as a contributor to β-cell dysfunction via the loss of cellular differentiation., (© 2024 John Wiley & Sons Ltd.)

Background: As the second most risky environmental pollution, noise imposes threats to human health. Exposure to high-intensity noise causes hearing impairment, psychotic disorders, endocrine modifications. The relationship among low-intensity noise, obesity and lipid-regulating nuclear factor PPARα is not yet clear., Methods: In this study, male wild-type (WT) and Pparα-null (KO) mice on a high-fat diet (HFD) were exposed to 75 dB noise for 12 weeks to explore the effect of low-intensity noise on obesity development and the role of PPARα. 3T3-L1 cells were treated with dexamethasone (DEX) and sodium oleate (OA) to verify the down-stream effect of hypothalamic-pituitary-adrenal (HPA) axis activation on the adipose tissues., Results: The average body weight gain (BWG) of WT mice on HFD exposed to noise was inhibited, which was not observed in KO mice. The mass and adipocyte size of adipose tissues accounted for the above difference of BWG tendency. In WT mice on HFD, the adrenocorticotropic hormone level was increased by the noise challenge. The aggravation of fatty liver by noise exposure occurred in both mouse lines, and the transport of hepatic redundant lipid to adipose tissues were similar. The lipid metabolism in adipose tissue driven by HPA axis accorded with the BWG inhibition in vivo, validated in 3T3-L1 adipogenic stem cells., Conclusion: Chronic exposure to low-intensity noise aggravated fatty liver in both WT and KO mice. BWG inhibition was observed only in WT mice, which covered up the aggravation of fatty liver by noise exposure. PPARα mediates the activation of HPA axis by noise exposure in mice on HFD. Elevated adrenocorticotropic hormone (ACTH) promoted lipid metabolism in adipocytes, which contributed to the disassociation of BWG and fatty liver development in male WT mice. Summary of PPARα suppresses noise-induced body weight gain in mice on high-fat-diet. Chronic exposure to low-intensity noise exposure inhibited BWG by PPARα-dependent activation of the HPA axis., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Fulminant hepatitis (FH) is a life-threatening clinical liver syndrome characterized by substantial hepatocyte necrosis and severe liver damage. FH is typically associated with severe oxidative stress, inflammation, and mitochondrial dysfunction. Pyrroloquinoline quinone (PQQ), a naturally occurring redox cofactor, functions as an essential nutrient and antioxidant and reportedly inhibits oxidative stress and exerts potent anti-inflammatory effects. In the present study, we aimed to evaluate the therapeutic efficacy of PQQ in murine hepatitis virus strain 3 (MHV-3)-induced FH and examined the underlying mechanism. An MHV-3-induced FH mouse model was established for in vivo examination . Liver sinusoidal endothelial cells (LSECs) were used for in vitro experiments. Herein, we observed that PQQ supplementation significantly attenuated MHV-3-induced hepatic injury by suppressing inflammatory responses and reducing oxidative stress. Mechanistically, PQQ supplementation ameliorated MHV-3-induced hepatic damage by down-regulating the Keap1/Nrf2 signaling pathway in vivo and in vitro. Furthermore, Nrf2 small interfering RNA targeting LSECs abrogated the PQQ-mediated protective effects against MHV-3-related liver injury. Our results deepen our understanding of the hepatoprotective function of PQQ against MHV-3-induced liver injury and provide evidence that alleviating oxidative stress might afford a novel therapeutic strategy for treating FH., Competing Interests: Conflict of interestAll authors declare no conflict of interests., (© The Author(s) 2024.)

To study the effects of caspase inhibitors on hemodynamics and inflammatory factors in acute respiratory distress syndrome (ARDS) model rats. Sixty healthy male Wistar rats were randomly divided into three groups, namely, the control group, ARDS group and ARDS + Caspase inhibitor group, with 20 rats in each group. The control group was intraperitoneally injected with 2 mL/kg saline, and the ARDS model group was established by intraperitoneally injecting 4 mg/kg Lipopolysaccharide (LPS), ARDS + Caspase inhibitor group was adminstered 20 mg/kg caspase inhibitor after intraperitoneal LPS injection. Changes in pulmonary arterial pressure (PAP) and mean arterial pressure (MAP) at 6 and 12 h before and after administration were recorded. Moreover, arterial blood gas was evaluated with a blood gas analyzer and changes in the partial pressure of O 2 (PaO 2 ), partial pressure of CO 2 (PaCO 2 ), partial pressure of O 2 /fraction of inspired O 2 (PaO 2 /FiO 2 ) were evaluated. In addition, the lung wet/dry weight (W/D) ratio and inflammatory factor levels in lung tissue were determined. Finally, pathological sections were used to determine the pulmonary artery media thickness (MT), MT percentage (MT%), and the degree of muscle vascularization. The pulmonary arterial pressure of rats was determined at several time points. Compared with the control group, the model group had a significantly increased pulmonary arterial pressure at each time point (P < 0.01), and the mean arterial pressure significantly increased at 6 h (P < 0.05). Compared with that of rats in the model group, the pulmonary arterial pressure of rats in drug administration group was significantly reduced at each time point after administration (P < 0.01), and the mean arterial pressure was significantly reduced at 6 h (P < 0.05). The arterial blood gas analysis showed that compared with those in the control group, PaO 2 , PaCO 2 and PaO 2 /FiO 2 in the model group were significantly reduced (P < 0.01), and PaO 2 , PaCO 2 and PaO 2 /FiO 2 were significantly increased after caspase inhibitor treatment (P < 0.05 or 0.01). The levels of the inflammatory mediators tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the model group were significantly higher than those in the control group (P < 0.01), and they were significantly decreased after caspase inhibitor treatment (P < 0.01). In the model group, pulmonary artery MT, MT% and the degree of muscle vascularization were significantly increased (P < 0.05 or 0.01), and pulmonary artery MT and the degree of muscle vascularization were significantly reduced after caspase inhibitor treatment (P < 0.05 or 0.01). Apoptosis Repressor with a Caspase Recuitment Domain (ARC) can alleviate the occurrence and development of pulmonary hypertension (PH) by affecting hemodynamics and reducing inflammation., (© 2024. The Author(s).)

Background/aim: Depression is associated with metabolic disorders, including non-alcoholic fatty liver disease (NAFLD). However, the mechanisms underlying the interaction between them are still poorly known., Materials and Methods: In this study, mice on a choline deficiency, L-amino acid-defined, high-fat diet (CDAHFD) developing steatosis were challenged with chronic restraint stress (CRS), a protocol widely used to induce depression. The development of depression and steatosis was evaluated using histopathology analysis, ELISA, q-PCR and Western Blot., Results: The contribution of the activated HPA axis to hepatic steatosis progress was fully established, which was validated using a hepatocyte model. Histopathological and biochemical analysis indicated that steatosis was exacerbated by CRS challenge, and behavioral tests indicated that the mice developed depression. Among the screened endocrinal pathways, the hypothalamic-pituitary-adrenal (HPA) axis was significantly activated and the synergistic effect of CDAHFD and CRS in activating the HPA axis was observed. In the hypothalamus, expression of corticotropin-releasing hormone (CRH) was increased by 86% and the protein levels of hypothalamic CRH were upregulated by 25% to 33% by CRS treatment. Plasma CRH levels were elevated by 45-56% and plasma adrenocorticotropic hormone (ACTH) levels were elevated by 29-58% by CRS treatment. In the liver, target genes of the HPA axis were activated, accompanied by disruption of the lipid metabolism and progression of steatohepatitis. The lipid metabolism in the Hepa1-6 cell line treated with endogenous corticosterone (CORT) was in accordance with the aforementioned in vivo responses., Conclusion: Depression aggravated hepatic steatosis in CDAHFD-fed mice by activating the HPA axis. The risk of NAFLD development should be fully considered in depressive patients and improvement of psychotic disorders could be an etiological treatment strategy for them., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: To investigate the therapeutic effect and mechanism of sivelestat sodium on acute lung injury (AIL)., Methods: A rat model for ALI/acute respiratory distress syndrome (ALI/ARDS) was established. Pathological examination of lung tissue was conducted to assess lung injury. Blood gas in the arteries was measured using a blood analyzer. Changes in PaO2, PaO2/FiO2, and lung wet/dry (W/D) weight ratio were carefully compared. ELISA assay was conducted to estimate cell adhesion and inflammation response. Finally, real-time reverse transcription polymerase chain reaction and western blotting assay was used to determine the activation of PI3K/AKT/mTOR pathway., Results: ARDS in vivo model was successfully constructed by LPS injection. Compared with the sham group, PaO2 and PaO2/FiO2 were significantly lower in the vehicle group, while the lung W/D ratio, the lung injury score, NE, VCAM-1, IL-8 andTNF-αwere significantly increased. After treatment with different doses of sivelestat sodium, we found PaO2, PaO2/FiO2 were prominently increased, while the lung W/D ratio, the lung injury score, NE, VCAM-1, IL-8, TNF-α levels were decreased in the dose-dependent manner. Meanwhile, compared with the vehicle group, the expression levels of Bax, PI3K, Akt and mTOR were significantly lower, and the expression of Bcl-2 was significantly higher after injection with sivelestat sodium., Conclusion: Sivelestat sodium has an interventional effect on ALI in sepsis by inhibiting the PI3K/AKT/mTOR signalling pathway., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Non-alcoholic steatohepatitis (NASH) is the hepatic manifestation of a cluster of conditions associated with lipid metabolism disorders. Ideal animal models mimicking the human NASH need to be explored to better understand the pathogenesis. A choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) has recently been used to induce the NASH model, but the advantages are not established. NASH models were induced using the well-known traditional methionine- and choline-deficient (MCD) diet for 5 weeks and the recently used CDAHFD for 3 weeks. Liver phenotypes were analyzed to evaluate the differences in markers related to NASH. Lipidomics and metabolism analyses were used to investigate the effects of dietary regimens on the lipidome of the liver. The CDAHFD induced stronger NASH responses than the MCD, including lipid deposition, liver injury, inflammation, bile acid overload and hepatocyte proliferation. A significant difference in the hepatic lipidome was revealed between the CDAHFD and MCD-induced NASH models. In particular, the CDAHFD reduced the hepatic levels of phosphatidylcholines (PCs) and acylcarnitines (ACs), which was supported by the metabolism analysis and in line with the tendency of human NASH. Pathologically, the CDAHFD could effectively induce a more human-like NASH model over the traditional MCD. The hepatic PCs, ACs and their metabolism in CDAHFD-treated mice were down-regulated, similar to those in human NASH.

Background: Tripterygium wilfordii has been widely used for the treatment of rheumatoid arthritis, which is frequently accompanied by severe gastrointestinal damage. The molecular mechanism underlying the gastrointestinal injury of Tripterygium wilfordii are yet to be elucidated., Methods: Transmission electron microscopy, and pathological and biochemical analyses were applied to assess intestinal bleeding. Metabolic changes in the serum and intestine were determined by metabolomics. In vivo (time-dependent effect and dose-response) and in vitro (double luciferase reporter gene system, DRATs, molecular docking, HepG2 cells and small intestinal organoids) studies were used to identify the inhibitory role of celastrol on intestinal farnesoid X receptor (FXR) signaling. Fxr-knockout mice and FXR inhibitors and agonists were used to evaluate the role of FXR in the intestinal bleeding induced by Tripterygium wilfordii., Results: Co-treatment with triptolide + celastrol (from Tripterygium wilfordii) induced intestinal bleeding in mice. Metabolomic analysis indicated that celastrol suppressed intestinal FXR signaling, and further molecular studies revealed that celastrol was a novel intestinal FXR antagonist. In Fxr-knockout mice or the wild-type mice pre-treated with pharmacological inhibitors of FXR, triptolide alone could activate the duodenal JNK pathway and induce intestinal bleeding, which recapitulated the pathogenic features obtained by co-treatment with triptolide and celastrol. Lastly, intestinal bleeding induced by co-treatment with triptolide and celastrol could be effectively attenuated by the FXR or gut-restricted FXR agonist through downregulation of the duodenal JNK pathway., Conclusions: The synergistic effect between triptolide and celastrol contributed to the gastrointestinal injury induced by Tripterygium wilfordii via dysregulation of the FXR-JNK axis, suggesting that celastrol should be included in the quality standards system for evaluation of Tripterygium wilfordii preparations. Determining the mechanism of the FXR-JNK axis in intestinal bleeding could aid in the identification of additional therapeutic targets for the treatment of gastrointestinal hemorrhage diseases. This study also provides a new standard for the quality assessment of Tripterygium wilfordii used in the treatment of gastrointestinal disorders., Competing Interests: Declaration of Competing Interest The authors declared no conflict of interest, (Copyright © 2023. Published by Elsevier GmbH.)

Background: Acute exposures to high levels of air pollutants are thought to be associated with hospitalization of patients with lung infection, while relatively little is known about the association between air pollutants and HOSPITAL ADMISSIONS FOR pulmonary sepsis., Objectives: To assess the correlation between low-level exposure to air pollutants and the hospitalizations for pulmonary sepsis in elderly patients., Methods: A total of 249 elderly patients with pulmonary sepsis from January 2018 to December 2020 in Shenzhen people's hospital were included. The data regarding hospitalizations for pulmonary sepsis, meteorological factors, and daily average levels of air pollutants on single-day lags (Lag0 to Lag7) in Shenzhen were collected. Low-level exposure was defined as the annual means of air pollutants below the levels of the Ambient Air Quality Standard (AAQS) in China (NO. GB3095-2012) and/or Global Air Quality Guidelines (AQG). A time-stratified case-crossover study design approach was used to evaluate the associations between exposure to air pollutants and incidence of the disease, univariate and multivariate logistic regression analysis to analyze the association between levels of air pollutants and hospitalizations for pulmonary sepsis in elderly patients., Results: Exposure to PM 1 (P = 0.007, Lag 2 day; P = 0.038, Lag6 day), PM 2.5 (P = 0.046, Lag2 day), PM 10 (P = 0.048, Lag4 day), and O 3 (P = 0.044, Lag6 day) was positively correlated with elevated risk of hospitalizations for pulmonary sepsis. In addition, logistic regression analysis revealed that exposure to PM 1 (OR = 1.833, 95%CI:1.032 ~ 3.256, Lag6 day) and O 3 (OR = 2.091, 95%CI:1.019 ~ 4.289, Lag6 day) were the independent risk factors of pulmonary sepsis in elderly patients., Conclusion: Our results demonstrate that short-term low-level exposure to PM 1 and O 3 could elevate the risk of hospitalizations for pulmonary sepsis in elderly patients in Shenzhen, providing evidence for developing early warning and screening systems for pulmonary sepsis., (© 2023. The Author(s).)

Objective: To analyze the clinical effect of high-flow nasal cannula (HFNC) oxygen therapy combined with naloxone on severe respiratory failure (SRF) in older adult patients., Methods: We enrolled 96 older adult patients with SRF who were admitted to Hai'an People's Hospital between February 2019 and March 2022. The patients were divided into two groups: the control group (treated with non-invasive positive pressure ventilation combined with naloxone) and the observation group (treated with HFNC oxygen therapy combined with naloxone). The blood gas measurement, respiratory rate (RR), St. George's Respiratory Questionnaire (SGRQ) score, Clara cell secreted protein (CC16) level, tumor necrosis factor-alpha (TNF-α) level, interleukin-1 (IL-1) level, length of intensive care unit (ICU) stay, tracheal intubation rate, and 28-day mortality rate were compared between the groups., Results: Blood gas measurement or RR did not differ significantly between the groups ( P >0.05). The observation group showed improved outcome, including reduced partial pressure of CO 2 , RR, and pH, and increased partial pressure of O 2 (PaO 2 ), PaO 2 /fraction of inspired O 2 ratio, and O 2 saturation after treatment ( P <0.05). Additionally, the observation group exhibited lower TNF-α level, IL-1 level, and SGRQ score, and higher CC16 level ( P <0.05). The length of ICU stay, tracheal intubation rate, and 28-day mortality rate were lower in the observation group ( P <0.05)., Conclusions: HFNC oxygen therapy combined with naloxone in older adult patients with SRF could improve blood gas results, disease duration, tracheal intubation rate, and 28-day mortality rate. This may occur through regulation of TNF-α, IL-1, and CC16 expression., Competing Interests: None., (AJTR Copyright © 2023.)

Objective: To analyze the clinical characteristics and risk factors of early acute liver injury in patients with heat stroke (HS), and to provide basis for early identification of HS-related liver injury and its pathogenesis in clinical practice., Methods: The clinical data of patients with HS admitted to the department of critical care medicine of Haian People's Hospital from June 2015 to August 2022 were retrospectively analyzed. The patients with HS were divided into early liver injury group and early non-liver injury group according to the occurrence of acute liver injury within 24 hours of admission. The differences of basic data, clinical data, laboratory indexes and clinical outcomes of the two groups were analyzed. Logistic regression was used to analyze the risk factors for early HS-related acute liver injury, and receiver operator characteristic (ROC) curves were drawn to evaluate their value in predicting the occurrence of early HS-related acute liver injury., Results: A total of 76 patients with HS were enrolled, and 46 patients with acute liver injury, accounting for 60.53%. In the early liver injury group, 14 patients (30.43%) had elevated aminotransferase alone, 9 patients (19.57%) had elevated total bilirubin (TBil) alone, and 23 patients (50.00%) had elevated both aminotransferase and TBil. Among the patients with elevated aminotransferases, 24 patients (64.87%) had mild elevation, 5 patients (13.51%) had moderate elevation, 8 patients (21.62%) had severe elevation. Compared with the early non-liver injury group, acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), arterial blood lactate (Lac), interleukin-6 (IL-6), procalcitonin (PCT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), TBil, γ-gamma glutamyl transferase (γ-GGT), lactate dehydrogenase (LDH), creatine kinase (CK), MB isoenzyme of creatine kinase (CK-MB), cardiac troponin I (cTnI), myoglobin (MYO), N-terminal B-type pro-brain natriuretic peptide (NT-proBNP), prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer in the early liver injury group were significantly increased, while platelet count (PLT) were significantly decreased within 24 hours after admission, the 28-day mortality was significantly increased [28.26% (13/46) vs. 6.67% (2/30)], and the differences were statistically significant (all P < 0.05). Univariate Logistic regression analysis showed that APACHE II score, SOFA score, PLT, Lac, IL-6, PCT, γ-GGT, LDH, CK, CK-MB, cTnI, MYO, PT, APTT, D-dimer were risk factors of early HS-related acute liver injury (all P < 0.05). Multivariate Logistic regression analysis showed that PLT, IL-6, and LDH were independent risk factors of early HS-related acute liver injury [odds ratio (OR) and 95% confidence interval (95%CI) were 0.986 (0.974-0.998), 1.027 (1.012-1.041), and 1.002 (1.000-1.004), all P < 0.05]. The ROC curve analysis showed that the area under the ROC curve (AUC) of PLT, IL-6 and LDH for predicting the occurrence of early HS-related acute liver injury was 0.672 (95%CI was 0.548-0.797), 0.897 (95%CI was 0.824-0.971) and 0.833 (95%CI was 0.739-0.927), respectively. IL-6 had the highest predictive value for early HS-related liver injury. When the optimal diagnostic threshold of IL-6 was 48.25 ng/L, the sensitivity was 95.7%, the specificity was 73.3%, and the predictive value of PLT was the lowest., Conclusions: The early HS-related liver injury is mainly manifested as the simultaneous elevation of aminotransferase and TBil, and most of cases are mild liver injury. PLT, IL-6 and LDH are independent risk factors of early HS-related acute liver injury.