Two-dimensional hydrophilic imprinted resin-graphene oxide composite for selective extraction and rapid determination of gibberellin traces in licorice samples.

This study presents novel methodologies and materials for selectively and sensitively determining gibberellin traces in licorice to address food safety concerns. A novel hydrophilic imprinted resin-graphene oxide composite (HMIR-GO) was developed with fast mass transfer, high adsorption capacity, and exceptional aqueous recognition performance for gibberellin. Leveraging the advantages of molecular imprinting, hydrophilic resin synthesis, and rapid mass transfer characteristics of GO, HMIR-GO was employed as an adsorbent, showing resistance to matrix interference. Coupled with HPLC, a rapid and selective method for determining gibberellin was established. Under optimal conditions, the method exhibited a wide linear range (0.02-5.00 µg g-1, r = 0.9999), low detection limits (3.3 ng g-1), and satisfactory recoveries (92.0-98.4%), enabling the accurate and rapid detection of gibberellin in licorice. This study introduces a pioneering strategy for the selective extraction and determination of trace gibberellin levels, offering insights for similar applications in functional foods.

Protein phosphatase 2A anchoring disruptor gene therapy for familial dilated cardiomyopathy.

Familial dilated cardiomyopathy is a prevalent cause of heart failure that results from the mutation of genes encoding proteins of diverse function. Despite modern therapy, dilated cardiomyopathy typically has a poor outcome and is the leading cause of cardiac transplantation. The phosphatase PP2A at cardiomyocyte perinuclear mAKAPß signalosomes promotes pathological eccentric cardiac remodeling, as is characteristic of dilated cardiomyopathy. Displacement of PP2A from mAKAPß, inhibiting PP2A function in that intracellular compartment, can be achieved by expression of a mAKAPß-derived PP2A binding domain-derived peptide. To test whether PP2A anchoring disruption would be effective at preventing dilated cardiomyopathy-associated cardiac dysfunction, the adeno-associated virus gene therapy vector AAV9sc.PBD was devised to express the disrupting peptide in cardiomyocytes in vivo. Proof-of-concept is now provided that AAV9sc.PBD improves the cardiac structure and function of a cardiomyopathy mouse model involving transgenic expression of a mutant α-tropomyosin E54K Tpm1 allele, while AAV9sc.PBD has no effect on normal non-transgenic mice. At the cellular level, AAV9sc.PBD restores cardiomyocyte morphology and gene expression in the mutant Tpm1 mouse. As the mechanism of AAV9sc.PBD action suggests potential efficacy in dilated cardiomyopathy regardless of the underlying etiology, these data support the further testing of AAV9sc.PBD as a broad-based treatment for dilated cardiomyopathy.

Unraveling the Mechanism of Xiaochaihu Granules in Alleviating Yeast-Induced Fever Based on Network Analysis and Experimental Validation.

Xiaochaihu granules (XCHG) are extensively used to treat fever. Nevertheless, the underlying mechanism remains elusive. This study aimed to explore the potential of XCHG in mitigating yeast-induced fever and the underlying metabolic pathways. The chemical composition of XCHG was ascertained using ultra-fast liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry (UFLC-Q-TOF-MS/MS), followed by integrated network analysis to predict potential targets. We then conducted experimental validation using pharmacological assays and metabolomics analysis in a yeast-induced mouse fever model. The study identified 133 compounds in XCHG, resulting in the development of a comprehensive network of herb-compound-biological functional modules. Subsequently, molecular dynamic (MD) simulations confirmed the stability of the complexes, including γ-aminobutyric acid B receptor 2 (GABBR2)-saikosaponin C, prostaglandin endoperoxide synthases (PTGS2)-lobetyolin, and NF-κB inhibitor IκBα (NFKBIA)-glycyrrhizic acid. Animal experiments demonstrated that XCHG reduced yeast-induced elevation in NFKBIA's downstream regulators [interleukin (IL)-1ß and IL-8], inhibited PTGS2 activity, and consequently decreased prostaglandin E2 (PGE2) levels. XCHG also downregulated the levels of 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), corticotropin releasing hormone (CRH), and adrenocorticotrophin (ACTH). These corroborated the network analysis results indicating XCHG's effectiveness against fever in targeting NFKBIA, PTGS2, and GABBR2. The hypothalamus metabolomics analysis identified 14 distinct metabolites as potential antipyretic biomarkers of XCHG. In conclusion, our findings suggest that XCHG alleviates yeast-induced fever by regulating inflammation/immune responses, neuromodulation, and metabolism modules, providing a scientific basis for the anti-inflammatory and antipyretic properties of XCHG.

Daphmacrimines A-K, Daphniphyllum alkaloids from Daphniphyllum macropodum Miq.

Daphmacrimines A-K (1-11) were isolated from the leaves and stems of Daphniphyllum macropodum Miq. Their structures and stereochemistries were determined by extensive techniques, including HRESIMS, NMR, ECD, IR, and single-crystal X-ray crystallography. Daphmacrimines A-D (1-4) are unprecedented Daphniphyllum alkaloids with a 2-oxazolidinone ring. Daphmacrimine I (9) contains a nitrile group, which is relatively rare in naturally occurring alkaloids. The abilities of daphmacrimines A-D and daphmacrimines G-K to enhance lysosomal biogenesis were evaluated through LysoTracker Red staining. Daphmacrimine K (11) can induce lysosomal biogenesis and promote autophagic flux.

Development of a nomogram to predict the prognosis of patients with secondary bone tumors in the intensive care unit: a retrospective analysis based on the MIMIC IV database.

PURPOSE: The present study aimed to develop a nomogram to predict the prognosis of patients with secondary bone tumors in the intensive care unit to facilitate risk stratification and treatment planning. METHODS: We used the MIMIC IV 2.0 (the Medical Information Mart for Intensive Care IV) to retrieve patients with secondary bone tumors as a study cohort. To evaluate the predictive ability of each characteristic on patient mortality, stepwise Cox regression was used to screen variables, and the selected variables were included in the final Cox proportional hazard model. Finally, the performance of the model was tested using the decision curve, calibration curve, and receiver operating characteristic (ROC) curve. RESULTS: A total of 1028 patients were enrolled after excluding cases with missing information. In the training cohort, albumin, APSIII (Acute Physiology Score III), chemotherapy, lactate, chloride, hepatic metastases, respiratory failure, SAPSII (Simplified Acute Physiology Score II), and total protein were identified as independent risk factors for patient death and then incorporated into the final model. The model showed good and robust prediction performance. CONCLUSION: We developed a nomogram prognostic model for patients with secondary bone tumors in the intensive care unit, which provides effective survival prediction information.

Downregulation of HMGB1 carried by macrophage-derived extracellular vesicles delays atherosclerotic plaque formation through Caspase-11-dependent macrophage pyroptosis.

BACKGROUND: Macrophage-derived extracellular vesicle (macrophage-EV) is highly studied for its regulatory role in atherosclerosis (AS). Our current study tried to elucidate the possible role of macrophage-EV loaded with small interfering RNA against high-mobility group box 1 (siHMGB1) affecting atherosclerotic plaque formation. METHODS: In silico analysis was performed to find critical factors in mouse atherosclerotic plaque formation. EVs secreted by RAW 264.7 cells were collected by ultracentrifugation and characterized, followed by the preparation of macrophage-EV-loaded siHMGB1 (macrophage-EV/siHMGB1). ApoE-/- mice were used to construct an AS mouse model by a high-fat diet, followed by injection of macrophage-EV/siHMGB1 to assess the in vivo effect of macrophage-EV/siHMGB1 on AS mice. RAW264.7 cells were subjected to ox-LDL, LPS or macrophage-EV/siHMGB1 for analyzing the in vitro effect of macrophage-EV/siHMGB1 on macrophage pyrophosis and inflammation. RESULTS: In silico analysis found that HMGB1 was closely related to the development of AS. Macrophage-EV/siHMGB could inhibit the release of HMGB1 from macrophages to outside cells, and the reduced HMGB1 release could inhibit foam cell formation. Besides, macrophage-EV/siHMGB also inhibited the LPS-induced Caspase-11 activation, thus inhibiting macrophage pyroptosis and preventing atherosclerotic plaque formation. CONCLUSION: Our results proved that macrophage-EV/siHMGB could inhibit foam cell formation and suppress macrophage pyroptosis, finally preventing atherosclerotic plaque formation in AS mice.

HIV-1 Nef acts in synergy with APOL1-G1 to induce nephrocyte cell death in a new Drosophila model of HIV-related kidney diseases.

Background: People carrying two APOL1 risk alleles (RA) G1 or G2 are at greater risk of developing HIV-associated nephropathy (HIVAN). Studies in transgenic mice showed that the expression of HIV-1 genes in podocytes, and nef in particular, led to HIVAN. However, it remains unclear whether APOL1-RA and HIV-1 Nef interact to induce podocyte cell death. Method: We generated transgenic (Tg) flies that express APOL1-G1 (derived from a child with HIVAN) and HIV-1 nef specifically in the nephrocytes, the fly equivalent of mammalian podocytes, and assessed their individual and combined effects on the nephrocyte filtration structure and function. Results: We found that HIV-1 Nef acts in synergy with APOL1-G1 resulting in nephrocyte structural and functional defects. Specifically, HIV-1 Nef itself can induce endoplasmic reticulum (ER) stress without affecting autophagy. Furthermore, Nef exacerbates the organelle acidification defects and autophagy reduction induced by APOL1-G1. The synergy between HIV-1 Nef and APOL1-G1 is built on their joint effects on elevating ER stress, triggering nephrocyte dysfunction and ultimately cell death. Conclusions: Using a new Drosophila model of HIV-1-related kidney diseases, we identified ER stress as the converging point for the synergy between HIV-1 Nef and APOL1-G1 in inducing nephrocyte cell death. Given the high relevance between Drosophila nephrocytes and human podocytes, this finding suggests ER stress as a new therapeutic target for HIV-1 and APOL1-associated nephropathies.

Management of retroperitoneal appendiceal perforation: a case report.

Retroperitoneal appendiceal perforation presents unique challenges in surgical management due to the complex nature of the retroperitoneal space. We present a case of a 57-year-old male with retroperitoneal appendiceal perforation, characterized by the presence of a large amount of gas in the retroperitoneal space. Emergent laparoscopic surgery was performed to address the retroperitoneal involvement. In retroperitoneal appendiceal perforation, surgical intervention and postoperative drainage are of great significance to prevent septic shock. The interconnectedness of the retroperitoneal space with other body regions is highlighted, underscoring the potential for severe complications. This case emphasizes the need for a tailored approach to managing retroperitoneal appendiceal perforation, preventing potential complications associated with this condition.

All-Round Ionic Liquids for Shuttle-Free Zinc-Iodine Battery.

The practical implementation of aqueous zinc-iodine batteries (ZIBs) is hindered by the rampant Zn dendrites growth, parasite corrosion, and polyiodide shuttling. In this work, ionic liquid EMIM[OAc] is employed as an all-round solution to mitigate challenges on both the Zn anode and the iodine cathode side. First, the EMIM+ embedded lean-water inner Helmholtz plane (IHP) and inert solvation sheath modulated by OAc- effectively repels H2 O molecules away from the Zn anode surface. The preferential adsorption of EMIM+ on Zn metal facilitates uniform Zn nucleation via a steric hindrance effect. Second, EMIM+ can reduce the polyiodide shuttling by hindering the iodine dissolution and forming an EMIM+ -I3 - dominated phase. These effects holistically enhance the cycle life, which is manifested by both Zn || Zn symmetric cells and Zn-I2 full cells. ZIBs with EAc deliver a capacity decay rate of merely 0.01 ‰ per cycle after over 18,000 cycles at 4 A g-1 , and lower self-discharge and better calendar life than the ZIBs without ionic liquid EAc additive.

Lightweight, Flexible, and Covalent-Bonding Phenolic Fabric Reinforced Phenolic Ablator for Thermal Insulation and Conformal Infrared Stealth.

Fiber-reinforced phenolic resin aerogel (FRPRA) composite materials are seductive candidates for high-temperature thermal protection owing to their low density, excellent thermostability, and thermal insulation. However, the intrinsic stiffness restricts their further application for high efficiency. We report a homogeneous and chemical bonding strategy for fabricating lightweight and flexible FRPRA with good ablative thermal insulation performance. The compressible (cyclic strain of 60%) and bendable (cyclic strain of 30%) abilities as well as the structural stability during ablation all benefit from the compatibility between the phenolic resin aerogel matrix and the phenolic fiber reinforcement. Additionally, low bulk density and thermal conductivity of 0.20 g cm-3 and 0.043 W m-1 K-1, respectively, endow the composite with efficient thermal insulation capability. With an 8 mm-thick coupon, the temperature of 200 °C can be decreased to 70.6 °C and the temperature around 1200 °C can be camouflaged to 78 °C through combining with the Al panel. The material also enables a conformal stealth of 600 °C based on its bendability. Hence, the composite has potential in applications of both static and dynamic thermal insulation.

Deep neural network for prediction of diet quality among doctors and nurses in North China during the COVID-19 pandemic.

Objective: The COVID-19 pandemic has placed unprecedented pressure on front-line healthcare workers, leading to poor health status, especially diet quality. This study aimed to develop a diet quality prediction model and determine the predictive effects of personality traits, socioeconomic status, lifestyles, and individual and working conditions on diet quality among doctors and nurses during the COVID-19 pandemic. Methods: A total of 5,013 doctors and nurses from thirty-nine COVID-19 designated hospitals provided valid responses in north China in 2022. Participants' data related to social-demographic characteristics, lifestyles, sleep quality, personality traits, burnout, work-related conflicts, and diet quality were collected with questionnaires. Deep Neural Network (DNN) was applied to develop a diet quality prediction model among doctors and nurses during the COVID-19 pandemic. Results: The mean score of diet quality was 46.14 ± 15.08; specifically, the mean scores for variety, adequacy, moderation, and overall balance were 14.33 ± 3.65, 17.99 ± 5.73, 9.41 ± 7.33, and 4.41 ± 2.98, respectively. The current study developed a DNN model with a 21-30-28-1 network framework for diet quality prediction. The DNN model achieved high prediction efficacy, and values of R2, MAE, MSE, and RMSE were 0.928, 0.048, 0.004, and 0.065, respectively. Among doctors and nurses in north China, the top five predictors in the diet quality prediction model were BMI, poor sleep quality, work-family conflict, negative emotional eating, and nutrition knowledge. Conclusion: During the COVID-19 pandemic, poor diet quality is prevalent among doctors and nurses in north China. Machine learning models can provide an automated identification mechanism for the prediction of diet quality. This study suggests that integrated interventions can be a promising approach to improving diet quality among doctors and nurses, particularly weight management, sleep quality improvement, work-family balance, decreased emotional eating, and increased nutrition knowledge.

Quantitative calculation of gases generation during low-temperature oxidation of coal.

The gases evolution during the low-temperature oxidation of coal is an essential parameter used to assess the state of coal oxidation and to estimate the gaseous pollutants. However, the current semi-quantitative method, which employs gas concentration as the measurement standard, is flawed. This paper presents a quantitative calculation method for gas products during coal oxidation. N2 is used as the tracer gas in the experiment, because nitrogen is an inert gas that will not participate in the reaction, and the amount of matter will not change in the reaction. According to the formula [Formula: see text], the corresponding mass flow rates of each gases component were calculated, and the gas yields during the reaction period were determined by comprehensive calculation. To this end, experiments were conducted on the low-temperature oxidation of coal using a flow reactor. After undergoing quantitative calculations, the main gas products' mass flow rates, yields, and energies, including CO, CO2, CH4, C2H4, C2H6, C2H2, and C3H8 between 30 and 180 °C were obtained. The findings showed that CO2 > CO > CH was generated in all the coal samples. The amount of gases produced in the low-temperature oxidation of coal is proportional to the level of oxygen concentration. When the oxygen concentration ranges from 0 to 21%, the gaseous production of MTH coal ranges from 381.44 g/ton to 8562.80 g/ton. The results of gaseous energy calculations showed that the energy loss for low temperature oxidation of the four coal samples ranged from 4334.14~26,772.73 kJ/ton under air atmosphere. Energy loss is also significantly affected by the oxygen concentration, and the energy loss of MTH coal increases significantly from 520.52 kJ/ton at 0% oxygen concentration to 26,772.73 kJ/ton at 21% oxygen concentration, an increase of about 50 times. Significantly, this method not only reflects the real gas evolution during low-temperature oxidation of coal but also computes the gas emission and energy loss, which is crucial for studying the mechanism of coal spontaneous combustion and assessing gases pollutants.

A host potassiophilicity strategy for unprecedentedly stable and safe K metal batteries.

Creating high-performance host materials for potassium (K) metal anodes remains a significant challenge due to the complex preparation process and poor K reversibility. In our work, we developed a potassiophilicity strategy using an oxygen-modified carbon cloth (O-CC) network as a host for K metal anodes. The O-CC network exhibited superior potassiophilic ability, and this improvement was also observed in other carbon hosts using the same process. The oxygen-induced epoxy group in the carbon network regulates interface electrons and enables strong binding of K adatoms through orbital hybridization, resulting in fewer side reactions with the electrolyte and promoting K-ion desolvation and uniform deposition. These factors result in unprecedented stability of the carbon network host, with a long lifespan of over 5500 hours at 0.5 mA cm-2/0.5 mA h cm-2 and 3500 h at 1 mA cm-2/0.5 mA h cm-2 in symmetric cells for K metal anodes, surpassing the cycle life of all previously reported K metal anodes. Furthermore, a high average coulombic efficiency of over 99.3% is demonstrated in O-CC//K cells during 210 cycles. The O-CC also exhibited a stable electrochemical performance, with a capacity retention of 73.3% in full cells coupled with a perylene-3,4,9,10-tetracarboxylic dianhydride cathode. We believe that this new strategy holds great promise for metal anodes in battery applications.

Association Between Benefit Finding and Self-care Management in Heart Failure Patient-Caregiver Dyads: The Mediating Role of Mutuality.

BACKGROUND: Inadequate self-care management has been reported in patients with heart failure (HF) and their family caregivers. However, evidence on the influencing factors and corresponding action paths for self-care management within a dyadic context is limited. OBJECTIVE: The aim of this study was to examine dyadic associations between benefit finding and self-care management in HF patient-caregiver dyads and the mediating role of mutuality in these associations. METHODS: This cross-sectional study was conducted in China, and a convenience sample of 253 HF patient-caregiver dyads was included in the analysis. Dyadic benefit finding and mutuality, patients' self-care management, and caregivers' contributions to self-care management were measured using self-reported questionnaires. The actor-partner interdependence model and actor-partner interdependence mediation model were adopted to analyze the data. RESULTS: Patients' benefit finding had an actor effect on their own self-care management (ß = 0.134, P < .05) and a partner effect on caregivers' contributions to self-care management (ß = 0.130, P < .05). Similarly, caregivers' benefit finding had an actor effect on their contributions to self-care management (ß = 0.316, P < .01) and a partner effect on patients' self-care management (ß = 0.187, P < .01). Moreover, patients' mutuality completely mediated the actor effect of their benefit finding on self-care management (ß = 0.127; 95% confidence interval, 0.032-0.233), and caregivers' mutuality partially mediated the actor effect of their benefit finding on contributions to self-care management (ß = 0.060; 95% confidence interval, 0.012-0.124). In addition, caregivers' mutuality completely mediated the partner effect of patients' benefit finding on caregivers' contributions to self-care management (ß = 0.036; 95% confidence interval, 0.009-0.081). CONCLUSIONS: The findings revealed the importance of benefit finding and mutuality, 2 modifiable factors positively associated with dyadic HF self-care management. Dyadic interventions targeting on enhancing benefit finding and mutuality should be designed and implemented to improve HF self-care management.

De novo CLPTM1 variants with reduced GABAA R current response in patients with epilepsy.

OBJECTIVE: To investigate the clinical features and potential pathogenesis mechanism of de novo CLPTM1 variants associated with epilepsy. METHODS: Identify de novo genetic variants associated with epilepsy by reanalyzing trio-based whole-exome sequencing data. We analyzed the clinical characteristics of patients with these variants and performed functional in vitro studies in cells expressing mutant complementary DNA for these variants using whole-cell voltage-clamp current recordings and outside-out patch-clamp recordings from transiently transfected human embryonic kidney (HEK) cells. RESULTS: Two de novo missense variants related to epilepsy were identified in the CLPTM1 gene. Functional studies indicated that CLPTM1-p.R454H and CLPTM1-p.R568Q variants reduced the γ-aminobutyric acid A receptor (GABAA R) current response amplitude recorded under voltage clamp compared to the wild-type receptors. These variants also reduced the charge transfer and altered the time course of desensitization and deactivation following rapid removal of GABA. The surface expression of the GABAA R γ2 subunit from the CLPTM1-p.R568Q group was significantly reduced compared to CLPTM1-WT. SIGNIFICANCE: This is the first report of functionally relevant variants within the CLPTM1 gene. Patch-clamp recordings showed that these de novo CLPTM1 variants reduce GABAA R currents and charge transfer, which should promote excitation and hypersynchronous activity. This study may provide insights into the molecular mechanisms of the CLPTM1 variants underlying the patients' phenotypes, as well as for exploring potential therapeutic targets for epilepsy.

Electrolyte and Interphase Engineering of Aqueous Batteries Beyond "Water-in-Salt" Strategy.

Aqueous batteries are promising alternatives to non-aqueous lithium-ion batteries due to their safety, environmental impact, and cost-effectiveness. However, their energy density is limited by the narrow electrochemical stability window (ESW) of water. The "Water-in-salts" (WIS) strategy is an effective method to broaden the ESW by reducing the "free water" in the electrolyte, but the drawbacks (high cost, high viscosity, poor low-temperature performance, etc.) also compromise these inherent superiorities. In this review, electrolyte and interphase engineering of aqueous batteries to overcome the drawbacks of the WIS strategy are summarized, including the developments of electrolytes, electrode-electrolyte interphases, and electrodes. First, the main challenges of aqueous batteries and the problems of the WIS strategy are comprehensively introduced. Second, the electrochemical functions of various electrolyte components (e.g., additives and solvents) are summarized and compared. Gel electrolytes are also investigated as a special form of electrolyte. Third, the formation and modification of the electrolyte-induced interphase on the electrode are discussed. Specifically, the modification and contribution of electrode materials toward improving the WIS strategy are also introduced. Finally, the challenges of aqueous batteries and the prospects of electrolyte and interphase engineering beyond the WIS strategy are outlined for the practical applications of aqueous batteries.

NiM (Sb, Sn)/N-doped hollow carbon tube as high-rate and high-capacity anode for lithium-ion batteries.

Alloy-type materials are regarded as prospective anode replacements for lithium-ion batteries (LIBs) owing to their attractive theoretical capacity. However, the drastic volume expansion leads to structural collapse and pulverization, resulting in rapid capacity decay during cycling. Here, a simple and scalable approach to prepare NiM (M: Sb, Sn)/nitrogen-doped hollow carbon tubes (NiMC) via template and substitution reactions is proposed. The nanosized NiM particles are uniformly anchored in the robust hollow N-doped carbon tubes via NiNC coordination bonds, which not only provides a buffer for volume expansion but also avoids agglomerating of the reactive material and ensures the integrity of the conductive network and structural framework during lithiation/delithiation. As a result, NiSbC and NiSnC exhibit high reversible capacities (1259 and 1342 mAh/g after 100 cycles at 0.1 A/g) and fascinating rate performance (627 and 721 mAh/g at 2 A/g), respectively, when employed as anodes of LIBs. The electrochemical kinetic analysis reveals that the dominant lithium storage behavior of NiMC electrodes varies from capacitive contribution to diffusion contribution during the cycling corresponding to the activation of the electrode exposing more NiM sites. Meanwhile, M (Sb, Sn) is gradually transformed into stable NiM during the de-lithium process, making the NiMC structure more stable and reversible in the electrochemical reaction. This work brings a novel thought to construct high-performance alloy-based anode materials.

Glutamine inhibits inflammation, oxidative stress, and apoptosis and ameliorates hyperoxic lung injury

Glutamine (Gln) is the most widely acting and abundant amino acid in the body and has anti-inflammatory properties, regulates body metabolism, and improves immune function. However, the mechanism of Gln’s effect on hyperoxic lung injury in neonatal rats is unclear. Therefore, this work focused on examining Gln’s function in lung injury of newborn rats mediated by hyperoxia and the underlying mechanism. We examined body mass and ratio of wet-to-dry lung tissue weights of neonatal rats. Hematoxylin and eosin (HE) staining was performed to examine histopathological alterations of lung tissues. In addition, enzyme-linked immunoassay (ELISA) was conducted to measure pro-inflammatory cytokine levels within bronchoalveolar lavage fluid (BALF). Apoptosis of lung tissues was observed using TUNEL assay. Western blotting was performed for detecting endoplasmic reticulum stress (ERS)-associated protein levels. The results showed that Gln promoted body weight gain, significantly reduced pathological damage and oxidative stress in lung tissue, and improved lung function in neonatal rats. Gln reduced pro-inflammatory cytokine release as well as inflammatory cell production in BALF and inhibited apoptosis in lung tissue cells. Furthermore, we found that Gln could downregulate ERS-associated protein levels (GRP78, Caspase-12, CHOP) and inhibit c-Jun N-terminal kinase (JNK) and inositol-requiring enzyme 1 alpha (IRE1α) phosphorylation. These results in an animal model of bronchopulmonary dysplasia (BPD) suggest that Gln may have a therapeutic effect on BPD by reducing lung inflammation, oxidative stress, and apoptosis and improving lung function; its mechanism of action may be related to the inhibition of the IRE1α/JNK pathway. (AU)

Glutamine inhibits inflammation, oxidative stress, and apoptosis and ameliorates hyperoxic lung injury.

Glutamine (Gln) is the most widely acting and abundant amino acid in the body and has anti-inflammatory properties, regulates body metabolism, and improves immune function. However, the mechanism of Gln's effect on hyperoxic lung injury in neonatal rats is unclear. Therefore, this work focused on examining Gln's function in lung injury of newborn rats mediated by hyperoxia and the underlying mechanism. We examined body mass and ratio of wet-to-dry lung tissue weights of neonatal rats. Hematoxylin and eosin (HE) staining was performed to examine histopathological alterations of lung tissues. In addition, enzyme-linked immunoassay (ELISA) was conducted to measure pro-inflammatory cytokine levels within bronchoalveolar lavage fluid (BALF). Apoptosis of lung tissues was observed using TUNEL assay. Western blotting was performed for detecting endoplasmic reticulum stress (ERS)-associated protein levels. The results showed that Gln promoted body weight gain, significantly reduced pathological damage and oxidative stress in lung tissue, and improved lung function in neonatal rats. Gln reduced pro-inflammatory cytokine release as well as inflammatory cell production in BALF and inhibited apoptosis in lung tissue cells. Furthermore, we found that Gln could downregulate ERS-associated protein levels (GRP78, Caspase-12, CHOP) and inhibit c-Jun N-terminal kinase (JNK) and inositol-requiring enzyme 1 alpha (IRE1α) phosphorylation. These results in an animal model of bronchopulmonary dysplasia (BPD) suggest that Gln may have a therapeutic effect on BPD by reducing lung inflammation, oxidative stress, and apoptosis and improving lung function; its mechanism of action may be related to the inhibition of the IRE1α/JNK pathway.

Hypericum japonicum extract inhibited porcine epidemic diarrhea virus in vitro and in vivo.

Porcine epidemic diarrhea virus (PEDV) infection causes lethal watery diarrhea and high mortality in neonatal piglets, leading to huge economic losses in the global swine industry. Currently, the existing commercial vaccines cannot fully control PEDV, so it is urgent to develop effective antiviral agents to complement vaccine therapy. In the present study, we investigated the antiviral effect of Hypericum japonicum extract (HJ) against PEDV in vivo and in vitro. In in vitro assays, HJ could directly inactivate PEDV strains; moreover, it inhibited the proliferation of PEDV strains in Vero or IPI-FX cells at its non-cytotoxic concentrations. Time of addition assays revealed that HJ mainly inhibited PEDV at the later stages of the viral life cycle. In in vivo, compared with the model group, HJ could reduce the viral titers in the intestines of infected piglets, and improve their intestinal pathological, indicating that HJ could protect the newborn piglets from highly pathogenic PEDV variant infection. Furthermore, this effect may be related to the fact that HJ can not only directly inhibit viruses, but also regulate the structure of intestinal microbiota. In conclusion, our results indicate that Hypericum japonicum could inhibit PEDV replication in vitro and in vivo and might possess the potential to develop as the anti-PEDV drug.