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Abstract Background Intestinal metaplasia (IM) is classified into complete intestinal metaplasia (CIM) and incomplete intestinal metaplasia (IIM). Patients diagnosed with IIM face an elevated susceptibility to the development of gastric cancer, underscoring the critical need for early screening measures. In addition to the complexities associated with diagnosis, the exact mechanisms driving the progression of gastric cancer in IIM patients remain poorly understood. OLFM4 is overexpressed in several types of tumors, including colorectal, gastric, pancreatic, and ovarian cancers, and its expression has been associated with tumor progression. Methods In this study, we used pathological sections from two clinical centers, biopsies of IM tissues, precancerous lesions of gastric cancer (PLGC) cell models, animal models, and organoids to explore the role of OLFM4 in IIM. Results Our results show that OLFM4 expression is highly increased in IIM, with superior diagnostic accuracy of IIM when compared to CDX2 and MUC2. OLFM4, along with MYH9, was overexpressed in IM organoids and PLGC animal models. Furthermore, OLFM4, in combination with Myosin heavy chain 9 (MYH9), accelerated the ubiquitination of GSK3β and resulted in increased β-catenin levels through the Wnt signaling pathway, promoting the proliferation and invasion abilities of PLGC cells. Conclusions OLFM4 represents a novel biomarker for IIM and could be utilized as an important auxiliary means to delimit the key population for early gastric cancer screening. Finally, our study identifies cell signaling pathways involved in the progression of IM.

Objective: This study aimed to assess the chemopreventive effect of ursodeoxycholic acid (UDCA) against COVID-19 and to analyze infection risk factors, symptoms, and recovery in outpatients with UDCA exposure.Methods: The study enrolled outpatients prescribed UDCA from the Second Affiliated Hospital of Chongqing Medical University, China, between 01 July 2022, and 31 December 2022. Data on demographics, comorbidities, and drug combinations were collected using electronic medical records. COVID-19 infection, symptoms, severity, prognosis, vaccinations, and UDCA administration were surveyed by telephone interviews. UDCA non-users served as controls and were matched in a 1:2 ratio with UDCA users using propensity score matching with the nearest neighbor algorithm. Infection rates, symptomatology, severity, and prognosis were compared between matched and control cohorts, and risk factors and infection and recovery symptoms were analyzed in UDCA-exposed outpatients.Results: UDCA-exposed outpatients (n = 778, 74.8%) and matched UDCA users (n = 95, 74.2%) showed significantly lower SARS-CoV-2 infection rates than control patients (n = 59, 92.2%) (p < 0.05). The matched UDCA group exhibited substantially lower fever, cough, sore throat, and fatigue rates than controls (p < 0.05). Participants with UDCA exposure generally experienced mild symptoms, while those without UDCA had moderate symptoms. The matched UDCA group also had significantly shorter durations of fever and cough (p < 0.05). Risk factors such as age over 60, less than 1 month of UDCA administration, diabetes mellitus, and coronary artery disease significantly increased SARS-CoV-2 infection rates (p < 0.05), while smoking led to a decrease (p < 0.05). Hypertension was associated with a prolonged COVID-19 recovery (p < 0.05), while smoking, vaccination, and fatty liver disease were associated with shorter recovery periods (p < 0.05). The main symptoms in the full UDCA cohort were fever, cough, and sore throat, with fatigue, cough, and hyposthenia being the most persistent.Conclusion: UDCA demonstrated chemopreventive effect against SARS-CoV-2 in outpatients by significantly reducing infection incidence and mitigating COVID-19 symptoms, severity, and recovery duration. Old age, short UDCA course, and comorbidities such as diabetes mellitus and CAD increased infection rates, while hypertension prolonged recovery. Smoking, vaccination, and fatty liver disease reduced infection rates and shortened recovery. UDCA had minimal impact on symptom types. Larger and longer-term clinical studies are needed further to assess UDCA’s effectiveness in COVID-19 prevention or treatment.

BackgroundChinese youth are at high risk for depression with a significantly higher detection rate of depression risk than other age groups, which brings about a huge challenge to the mental health work of universities. Developing supportive resources that promote resilience against adverse environmental influences in high-risk groups is quite more urgent than medical treatment for firm diagnoses of mental issues that have developed into depression in the current background.MethodsA total of 665 university students in China completed self-reported questionnaires measuring psychological resilience, social support, and coping styles. The structural equation model testing on the goodness of fit of the theoretical framework was first performed. Descriptive statistics and Pearson’s correlation analysis among social support, resilience, and coping styles were then conducted. At last, we tested the mediating role of coping styles.ResultsSocial support has a significant positive effect on the psychological resilience of the youth. Mixed coping and immature coping styles have significant negative impacts on both social support and resilience, while mature coping styles have a significant positive effect on social support and resilience. Mature and immature coping styles mediate the association between social support and resilience in youth.ConclusionBased on stress theory, this study explores mechanisms that facilitate the development of resilience in young people with regard to social support and coping styles. The current research depicts an interventional perspective of building a social support network that guides the youth to adopt mature coping styles to enhance their resilience and facilitate their mental health.

Abstract Background Arteriosclerosis in multiple arteries has long been associated with heightened cardiovascular risk. Acetaldehyde dehydrogenase 2 (ALDH2) and methylenetetrahydrofolate reductase (MTHFR) play an important role in the pathogenesis of arteriosclerosis by participating in the oxidation and reduction reactions in vascular endothelial cells. The purpose was to investigate the relationship of ALDH2 and MTHFR gene polymorphisms with arteriosclerosis in multiple arteries. Methods 410 patients with arteriosclerosis in single artery and 472 patients with arteriosclerosis in multiple arteries were included. The relationship between ALDH2 rs671 and MTHFR rs1801133 polymorphisms and arteriosclerosis in single artery and arteriosclerosis in multiple arteries was analyzed. Results The proportion of ALDH2 rs671 A allele (35.6% vs. 30.9%, P = 0.038) and MTHFR rs1801133 T allele (32.6% vs. 27.1%, P = 0.012) in patients with arteriosclerosis in multiple arteries was significantly higher than that in arteriosclerosis in single artery, respectively. The proportion of history of alcohol consumption in patients with ALDH2 rs671 G/G genotype was higher than those in ALDH2 rs671 G/A genotype and A/A genotype (P

Background and aims: Type 2 diabetes mellitus remains a substantial medical problem with increasing global prevalence. Pharmacological research is becoming increasingly focused on personalized treatment strategies. Drug development based on glucokinase (GK) activation is an important strategy for lowering blood glucose. This study aimed to investigate the effect of GK activation on glucose and lipid metabolism in diet-induced obese mice. Materials and methods: Mice were fed with a high-fat diet (HFD) for 16 weeks to induce obesity, followed by a GK activator (GKA, AZD1656) or vehicle treatment by gavage for 4 weeks. The effect of GKA treatment on glucose metabolism was evaluated using glucose and insulin tolerance tests. Hepatic lipid accumulation was assessed by hematoxylin and eosin staining, Oil Red O staining, and transmission electron microscopy. The underlying mechanism of GK activation in glucose and lipid metabolism in the liver was studied using transcriptomic analysis, with a mechanistic study in mouse livers in vivo and AML12 cells in vitro. Results: GK activation by GKA treatment improved glucose tolerance in HFD-fed mice while increasing hepatic lipid accumulation. Transcriptomic analysis of liver tissues indicated the lipogenesis and protein kinase RNA-like endoplasmic reticulum kinase (PERK)-unfolded protein response (UPR) pathway activations in GKA-treated HFD-fed mice. Inhibition of the ACC activity, which is an important protein in lipogenesis, attenuated GKA treatment-induced lipid accumulation and PERK-UPR activation in vitro. Conclusions: GK activation improved glucose tolerance and insulin sensitivity while inducing hepatic lipid accumulation by increasing the lipogenic gene expression, which subsequently activated the hepatic PERK-UPR signaling pathway.

Abstract Background Genetic factors have a certain proportion in the risk factors of hypertension. The purpose was to investigate the relationship of cytochrome P450 2C19 (CYP2C19) polymorphisms with hypertension in Hakka population. Methods The study included 1,872 hypertensive patients and 1,110 controls. The genotypes of CYP2C19 rs4244285 and rs4986893 of all individuals were detected and analyzed. Results The genotype and allele distributions of CYP2C19 rs4244285 were significantly different between hypertension group and control group. The CYP2C19 *1/*1 genotype was the most predominant among the subjects (40.8%), followed by the CYP2C19 *1/*2 genotype (40.5%). The percentage of CYP2C19*1, *2, and *3 allele was 64.2%, 30.8%, and 5.0%, respectively. The proportion of intermediate metabolizers (IM) (49.3% vs. 42.9%), poor metabolizers (PM) (14.3% vs. 8.9%) (P

Abstract Objective To explore the impact of artificial-intelligence perceptual learning when performing the ultrasound-guided popliteal sciatic block. Methods This simulation-based randomized study enrolled residents who underwent ultrasound-guided sciatic nerve block training at the Department of Anesthesiology of Beijing Jishuitan Hospital between January 2022 and February 2022. Residents were randomly divided into a traditional teaching group and an AI teaching group. All residents attended the same nerve block theory courses, while those in the AI teaching group participated in training course using an AI-assisted nerve identification system based on a convolutional neural network instead of traditional training. Results A total of 40 residents were included. The complication rates of paresthesia during puncture in the first month of clinical sciatic nerve block practice after training were significantly lower in the AI teaching group than in the traditional teaching group [11 (4.12%) vs. 36 (14.06%), P = 0.000093]. The rates of paresthesia/pain during injection were significantly lower in the AI teaching group than in the traditional teaching group [6 (2.25%) vs. 17 (6.64%), P = 0.025]. The Assessment Checklist for Ultrasound-Guided Regional Anesthesia (32 ± 3.8 vs. 29.4 ± 3.9, P = 0.001) and nerve block self-rating scores (7.53 ± 1.62 vs. 6.49 ± 1.85, P

Objective: To investigate the effects of Erector Spinae Plane Block (ESPB) and Retrolaminar Block (RLB) on intra- and postoperative analgesia in patients with Multiple Rib Fractures (MRFs). Methods: A total of 80 MRFs patients were randomly divided into the ESPB (Group E) and RLB (Group R) groups. After general anesthesia, ESPB and RLB were performed under ultrasound guidance, respectively, together with 20 mL of 0.5% ropivacaine and Patient-Controlled Intravenous Analgesia (PCIA). Results: Thirty-four cases in Group E and 33,cases in Group R showed unclear paravertebral spaces. The intraoperative dosage of remifentanil (mean ± SD) (392.8 ± 118.7 vs. 501.7 ± 190.0 μg) and postoperative morphine PCIA dosage, (7.35 ± 1.55 vs. 14.73 ± 2.18 mg) in Group R were significantly less than those in Group E; the Visual Analog Scale (VAS) scores in Group R at 2 (2.7 ± 1.2 vs. 3.4 ± 1.4), 4 (2.2 ± 1.1 vs. 2.8 ± 0.9), 12 (2.5 ± 0.9 vs. 3.0 ± 0.8), and 24 hours (2.6 ± 1.0 vs. 3.1 ± 0.9) after surgery were significantly lower than those in Group E. Finally, the normal respiratory diaphragm activity (2.17 ± 0.22 vs. 2.05 ± 0.19), pH (median [IQR] (7.38 [7.31–7.45] vs. 7.36 [7.30–7.42]), and partial pressure of carbon dioxide (PaCO2) (44 [35–49] vs. 42.5 [30–46]) after the operation in Group R were significantly better than those in Group E (p < 0.05). Conclusions: RLB was a more effective analgesic method than ESPB in the treatment of MRF.

Phytomelatonin is a pleiotropic signaling molecule that regulates plant growth, development, and stress response. In plant cells, phytomelatonin is synthesized from tryptophan via several consecutive steps that are catalyzed by tryptophan decarboxylase (TDC), tryptamine 5-hydroxylase (T5H), serotonin N-acyltransferase (SNAT), and N-acetylserotonin methyltransferase (ASMT) and/or caffeic acid-3-O-methyltransferase (COMT). Recently, the identification of the phytomelatonin receptor PMTR1 in Arabidopsis has been considered a turning point in plant research, with the function and signal of phytomelatonin emerging as a receptor-based regulatory strategy. In addition, PMTR1 homologs have been identified in several plant species and have been found to regulate seed germination and seedling growth, stomatal closure, leaf senescence, and several stress responses. In this article, we review the recent evidence in our understanding of the PMTR1-mediated regulatory pathways in phytomelatonin signaling under environmental stimuli. Based on structural comparison of the melatonin receptor 1 (MT1) in human and PMTR1 homologs, we propose that the similarity in the three-dimensional structure of the melatonin receptors probably represents a convergent evolution of melatonin recognition in different species.

Abstract MALAT1-associated small cytoplasmic RNA (mascRNA) is a cytoplasmic tRNA-like small RNA derived from nucleus-located long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). While MALAT1 was extensively studied and was found to function in multiple cellular processes, including tumorigenesis and tumor progression, the role of mascRNA was largely unknown. Here we show that mascRNA is upregulated in multiple cancer cell lines and hepatocellular carcinoma (HCC) clinical samples. Using HCC cells as model, we found that mascRNA and its parent lncRNA MALAT1 can both promote cell proliferation, migration, and invasion in vitro. Correspondingly, both of them can enhance the tumor growth in mice subcutaneous tumor model and can promote metastasis by tail intravenous injection of HCC cells. Furthermore, we revealed that mascRNA and MALAT1 can both activate ERK/MAPK signaling pathway, which regulates metastasis-related genes and may contribute to the aggressive phenotype of HCC cells. Our results indicate a coordination in function and mechanism of mascRNA and MALAT1 during development and progress of HCC, and provide a paradigm for deciphering tRNA-like structures and their parent transcripts in mammalian cells.

Alzheimer's disease (AD) is a neurodegenerative disorder mainly affecting old population. In this study, two Tau overexpressing cell lines (SH-SY5Y/Tau and HEK293/Tau), N2a/SweAPP cell line, and 3× Transgene (APPswe/PS1M146V/TauP301L) mouse primary nerve cell lines were used as AD models to study the activity and molecular mechanism of macelignan, a natural compound extracted from Myristica fragrans, against AD. Our study showed that macelignan could reduce the phosphorylation of Tau at Thr 231 site, Ser 396 site, and Ser 404 site in two overexpressing Tau cell lines. It also could decrease the phosphorylation of Tau at Ser 404 site in mouse primary neural cells. Further investigation of its mechanism found that macelignan could reduce the phosphorylation of Tau by increasing the level of autophagy and enhancing PP2A activity in Tau overexpressing cells. Additionally, macelignan could activate the PERK/eIF2α signaling pathway to reduce BACE1 translation, which further inhibits the cleavage of APP and ultimately suppresses Aβ deposition in N2a/SweAPP cells. Taken together, our results indicate that macelignan has the potential to be developed as a treatment for AD.

As the preferred material for the first wall of fusion reactors, China’s low-activation martensitic (CLAM) steel has several advantages; however, its high-temperature (>550 ℃) strength is not enough, and the helium produced by fusion can easily form a thick helium bubble and gather at the boundary, which leads to helium embrittlement; thus, the low-activation ferrite/martensite steel cannot effectively function in the fusion reactor working environment. Previous studies have shown that adding nano-sized oxide strengthening phase into CLAM steel can significantly improve the high-temperature strength and irradiation resistance of the steel, and Y2O3, Al2O3, or ThO2 are commonly used as strengthening phases. Moreover, it has been found that adding Ti will result in a better strengthening effect. In this study, CLAM steel with the addition of Y2Ti2O7 nanoparticles was fabricated using a vacuum induction furnace. Afterward, the effect of Y2Ti2O7 nanoparticles on inclusions in CLAM steel was investigated via scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), and a universal testing machine experiment; then, the mechanical properties of CLAM steel were analyzed. The results show that Y2Ti2O7+Fe nanoparticles are successfully added to CLAM steel. The inclusion size of CLAM steel is 0.5−1.5 μm. The inclusion morphology is near-spherical, and the inclusion composition is Y–Ti–O–Mn–C–Ta–W–V–Cr–Fe; thus, the inclusion is characterized as a compound inclusion, mainly because Ta and V are strong carbide-forming elements and some Y2Ti2O7 particles may agglomerate. When the Y2Ti2O7 content is 0.5%, the inclusions in the steel modify into composite inclusions of rare-earth oxides, and the steel strength is 1356 MPa, while the elongation and section shrinkage are 13.44% and 63.15%, respectively. Moreover, second-phase particles also exist in the fracture dimples. The particles are spherical, less than 1 μm and have a complex composition, mainly Y–Ti–O–C–Ta–W phase.

The genotype CR60 is a spontaneous Cherry Red variant (containing granular red dapples on flue-cured leaves) of the Yunyan 87 (Y87) tobacco; it accumulates higher concentration of iron (Fe) in leaves than Y87, but the physiological differences between them remain largely unknown. We investigated the physiological and molecular mechanisms of CR60 in response to Fe deficiency under hydroponic conditions. Our results showed no significant phenotypic difference between Y87 and CR60 at optimal (40 μM) and high Fe (160 and 320 μM) concentrations. By contrast, CR60 exhibited higher tolerance to Fe deficiency (0 μM) than Y87, as shown by higher concentrations of chlorophyll in CR60 leaves after 21-day Fe-deficiency stress. Transcriptome profiling coupled with RT-PCR analyses found that the expression of IRT1 and several genes associated with chlorophyll biosynthesis and photosynthesis (e.g., PRO, GSA, FD1, PsbO, and PC) was higher in CR60 than Y87. These results indicated that CR60 maintains sufficient Fe uptake, chlorophyll biosynthesis and photosynthetic rate when subjected to Fe starvation.

Fracture failure of super 13Cr can occur in complex and harsh environments such as high temperature, high pressure, and corrosive gas wells, which damages the economic benefit of oil and gas development and also poses a great threat to wellbore integrity. Therefore, it is urgent to study the corrosion mechanism of super 13Cr tubing in oil and gas wells, and this study performed an on-site experimental analysis on failed super 13Cr tubing, employing the microarea electrochemical scanning Kelvin probe (SKP) method to investigate the causes of corrosion of super 13Cr material. In addition, the thermodynamics of the mechanism by which pits turn into cracks was examined in light of the experimental findings on the nucleation and development of pitting corrosion. The findings reveal scale and clear pits on the surface of the failed super 13Cr tubing and that CaCO3 as well as FeCO3 are the scale’s primary constituents. According to the SKP scan results, the super 13Cr tubing has a risk of pitting under wells, and the galvanic cell with microcorrosion is the primary cause of pitting corrosion, which also shows that the potential difference between the anode area and the cathode area of the super 13Cr material gradually increases with the increase in immersion time. Under the autocatalytic effect of the occlusive corrosion cell and the applied load, the corrosion pits and cracks of super 13Cr tubing propagate, eventually leading to tubing breaks and failure.

Background: Circadian rhythm disturbance is common postoperatively in older patients with hip fractures, which may contribute to the development of postoperative delirium (POD). As a reliable biomarker of endogenous circadian rhythms, melatonin regulates the sleep-wake cycle and environmental adaptation, and its secretory rhythm may be modified by anaesthesia and surgery. This study compared the impact of subarachnoid anaesthesia (SA) and general anaesthesia (GA), on the peak of melatonin secretion (primary outcome), the circadian rhythm of melatonin, cortisol and sleep, and the POD incidence (secondary outcome). Methods: In this prospective cohort observational study, hip fracture surgery patients were enrolled and assigned to receive either SA or GA. Postoperative plasma melatonin and cortisol levels were dynamically measured every six hours on seven time-points, and the circadian rhythm parameters including mesor, amplitude, and acrophase were calculated. Subjective and objective sleep assessments were performed by sleep diaries and sleep trackers, respectively. The Confusion Assessment Method was used twice daily by a specific geriatrician to screen for POD occurrence. Findings: In a cohort of 138 patients who underwent hip fracture surgery, the circadian rhythm disruption of the patients in the GA group (n=69) was greater than the SA group (n=69). Compared with SA, GA provided the lower peak concentration, mesor, and amplitude of melatonin secretion on postoperative day 1 (p < 0.05). Patients in the GA group experienced higher awakenings, more sleep deprivation, and poor sleep quality on surgery day (p < 0.05). A proportion of 12 patients in the SA group (17.4%) and 24 patients in the GA group (34.8%) experienced POD (p = 0.020). Interpretation: These results suggest that SA may be superior to GA in elderly patients undergoing hip fracture surgery as SA is associated with less impairment of the melatonin rhythm and sleep patterns, and fewer POD occurrences.

This study was performed to determine the antifungal activity of loquat (Eriobotrya japonica Lindl) leaf extract (LLE) against the citrus postharvest pathogen Penicillium digitatum (P. digitatum). The LLE exhibited an antifungal activity against P. digitatum, with a minimum inhibitory concentration (MIC) of 0.625 mg/ml and a minimum fungicidal concentration (MFC) of 1.25 mg/ml. Significant inhibitory effects of LLE on mycelial growth and spore germination of P. digitatum were seen in a dose-dependent manner. Simultaneously, to investigate possible antifungal mechanisms by LLE, we analyzed their influence on morphological changes, cell membrane permeability, cell wall and cell membrane integrity, and adenosine phosphates (ATP, ADP, and AMP) levels. Alterations, such as sunken surface and malformation, occurred in the LLE-treated P. digitatum spores. Furthermore, intracellular inclusion content decreased after LLE treatment, indicating an increase in cell membrane permeability. Besides, the LLE treatment induced a significant decline in the level of adenosine monophosphate (AMP), adenosine diphosphate (ADP), and adenosine triphosphate (ATP) with a noticeable addition of extracellular ATP, ADP, and AMP during the entire treatment period. Overall, the results manifested that the antifungal activity of LLE against P. digitatum can be attributed to the derangement of cell membrane permeability and disordered energy metabolism. This is the first report on the mechanism of antifungal activity of LLE and could be useful in the development of targeted fungicides from natural origin.

Introduction and objectives: Alcoholic hepatitis (AH) is characterized by high morbidity and mortality. MicroRNA-494-3p is possibly involved in the regulation of cancers, but its role in AH has been rarely studied. Materials and methods: AH mice model and primarily cultured mice hepatic stellate cells (HSCs) model were constructed. Levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were analyzed by ELISA. Expressions of miRNAs, HSC activation-related proteins and fibrosis-related protein were analyzed by qRT-PCR and Western blot. Cell counting kit, colony formation and flow cytometry assays were used to detect cell viability, proliferation and apoptosis, respectively. The relationship between TNF receptor-associated factor 3 (TRAF3) and miR-494-3p was predicted and verified by TargetScan and dual-luciferase assay, respectively. Results of the above experiments were verified by rescue experiments using TRAF3. Results: Liver damage and miRNA expression were observed in AH mice, and AST and ALT levels were increased in serum of AH mice. MiR-494-3p was reduced in AH liver tissues, and it decreased the levels of α-SMA and fibrosis-related proteins. HSCs were isolated, and activating HSCs or upregulating miR-494-3p had a regulatory effect on the levels of miR-494-3p, HSC activation-related proteins and fibrosis-related proteins as well as cell viability, proliferation and apoptosis. In addition, miR-494-3p targeted TRAF3 and inhibited TRAF3 expression, while overexpressed TRAF3 promoted TRAF3 expression and rescued the regulatory effect of miR-494-3p on the levels of related proteins as well as cell viability, proliferation and apoptosis. Conclusions: This study provided a novel mechanistic comprehension of the anti-fibrotic effect of miR-494-3p.

Sea cucumbers are valuable marine foods as well as a source of traditional medicines with various bioactivities. Macrophage activation by small-molecule oligopeptides obtained from the sea cucumber Apostichopus japonicus (SCOP) were investigated. After SCOP were proven nontoxic by oral administration and CCK-8 assays, we measured immune-stimulatory mRNA, pro-inflammatory cytokines, and NO production levels and determined the molecular mechanism of macrophage stimulation. Our results demonstrated that SCOP upregulated both the mRNA levels and the secretion of NO, TNF-α, and IL-6 in a dose-dependent manner. More importantly, SCOP contributed to the stimulation of macrophages through the upregulation of the NF-κB and MAPK signaling pathways. Taken together, these results indicated that SCOP exerted macrophage activation effects on RAW264.7 cells and that they could potentially be used as a functional food supplement in treating immune suppression.

Polymannuronate (PM) is an acidic polymer separated from alginate. PM is a linear block polysaccharide in edible brown algae that has been widely used in the food industry. Seleno-polymannuronate (Se-PM) is a seleno-derivative of PM synthesized from PM and Na2SO3 in our laboratory. We investigated the anti-neuroinflammatory activity of Se-PM in lipopolysaccharide (LPS)-activated primary microglia and astrocytes and a mouse model of acute inflammation. Our results show that Se-PM could markedly reduce NO and PGE2 production, iNOS and COX-2 expression, and TNF-α, IL-1β and IL-6 secretion in LPS-treated primary microglia and astrocytes. Moreover, the LPS-triggered overactivation of NF-κB and MAPK signalling was attenuated by Se-PM. In addition, in vivo, LPS-induced microglial and astrocytic activation was remarkably suppressed by Se-PM. These results suggest that Se-PM merits exploration as an alternative medicinal or functional food for alleviating neuroinflammation.

Abstract Background The advent of human-induced pluripotent stem cells holds great promise for producing ample individualized hepatocytes. Although previous efforts have succeeded in generating hepatocytes from human pluripotent stem cells in vitro by viral-based expression of transcription factors and/or addition of growth factors during the differentiation process, the safety issue of viral transduction and high cost of cytokines would hinder the downstream applications. Recently, the use of small molecules has emerged as a powerful tool to induce cell fate transition for their superior stability, safety, cell permeability, and cost-effectiveness. Methods In the present study, we established a novel efficient hepatocyte differentiation strategy of human pluripotent stem cells with pure small-molecule cocktails. This method induced hepatocyte differentiation in a stepwise manner, including definitive endoderm differentiation, hepatic specification, and hepatocyte maturation within only 13 days. Results The differentiated hepatic-like cells were morphologically similar to hepatocytes derived from growth factor-based methods and primary hepatocytes. These cells not only expressed specific hepatic markers at the transcriptional and protein levels, but also possessed main liver functions such as albumin production, glycogen storage, cytochrome P450 activity, and indocyanine green uptake and release. Conclusions Highly efficient and expedited hepatic differentiation from human pluripotent stem cells could be achieved by our present novel, pure, small-molecule cocktails strategy, which provides a cost-effective platform for in vitro studies of the molecular mechanisms of human liver development and holds significant potential for future clinical applications.

Abstract Alginate, a natural acidic polysaccharide extracted from marine brown seaweeds, is composed of different blocks of β-(1, 4)-D-mannuronate (M) and its C-5 epimer α-(1, 4)-L-guluronate (G). Alginate-derived guluronate oligosaccharide (GOS) readily activates macrophages. However, to understand its role in immune responses, further studies are needed to characterize GOS transport and signalling. Our results show that GOS is recognized by and upregulates Toll-like receptor 4 (TLR4) on RAW264.7 macrophages, followed by its endocytosis via TLR4. Increased expression of TLR4 and myeloid differentiation protein 2 (MD2) results in Akt phosphorylation and subsequent activation of both nuclear factor-κB (NF-κB) and mechanistic target of rapamycin (mTOR). Moreover, GOS stimulates mitogen-activated protein kinases (MAPKs); notably, c-Jun N-terminal kinase (JNK) phosphorylation depends on TLR4 initiation. All these events contribute to the production of inflammatory mediators, either together or separately. Our findings also reveal that GOS induces cytoskeleton remodelling in RAW264.7 cells and promotes macrophage proliferation in mice ascites, both of which improve innate immunity. Conclusively, our investigation demonstrates that GOS, which is dependent on TLR4, is taken up by macrophages and stimulates TLR4/Akt/NF-κB, TLR4/Akt/mTOR and MAPK signalling pathways and exerts impressive immuno-stimulatory activity.

α-Mangostin, a xanthone derivative from the pericarp of mangosteen, exerts both anti-proliferative and cytotoxic effects on various cancers. However, the effect of α-mangostin on hepatocellular carcinoma (HCC) cells has not yet been fully determined. Therefore, the present study investigated the anti-proliferative effect of α-mangostin on HCC cells. α-Mangostin inhibited the proliferation of HCC and malignantly transformed hepatic cells. In addition, α-mangostin induced G0/G1 phase cell cycle arrest. Furthermore, α-mangostin also reversed doxorubicin-resistance in the HCC cells induced by IL-6. Moreover, the percentage of CD133, CD44 and EpCAM positive stem-like HCC cells treated with α-mangostin was reduced. The expression of key stemness transcription factors, such as Bmi-1, c-Myc and Nanog, were also suppressed following α-mangostin treatment. In conclusion, α-mangostin has been shown to have anti-proliferative effects in HCC cells and malignantly transformed hepatic cells. This work discovered the potential effect of α-mangostin in HCC prevention and treatment.

Magnetic carbonaceous nanomaterials are needed in water treatment applications because they can offer both carbon surfaces for sorption of organic pollutants and ease of material magnetic retrieval for regeneration and reuse. In this study, we employed a facile one-step method to synthesize a black carbon-magnetite composite (BC-Mag) by high-temperature annealing of black carbon and hematite. The nanocomposite was easily dispersed and stable in water owing to the presence of negatively charged oxygen surface functional groups. Sorption kinetics with dissolved carbamazepine showed a rapid initial uptake with equilibrium achieved within only minutes. The sorption extent can be described with the Freundlich model, and surface area normalized sorption affinity was an order of magnitude greater than conventional granular activated carbon. The sorption extent of neutral carbamazepine remained constant between pH 2−10 while surface zeta potential decreased. BC-Mag can be reused for the sorption of carbamazepine up to six times without significant loss of the sorption extent.

Pinocembroside (PiCB) isolated from Ficus hirta Vahl. fruit was studied herein with the aim to find the potential mechanism for significant inhibition of growth of Penicillium digitatum, a causative pathogen of citrus green mold disease. PiCB substantially inhibited mycelial growth of P. digitatum, with the observed half maximal effective concentration (EC50), minimum inhibitory concentration (MIC), and minimum fungicidal concentration (MFC) of 120.3, 200, and 400 mg/L, respectively. Moreover, PiCB altered hyphal morphology and cellular morphology by breaking and shrinking of mycelia, decomposing cell walls, cytoplasmic inclusions. In addition to, a non-targeted metabolomics analysis by UHPLC-Q-TOF/MS was also performed, which revealed that PiCB treatment notably disrupted the metabolisms of amino acids, lipids, fatty acids, TCA, and ribonucleic acids, thereby contributing to membrane peroxidation. Current findings provide a new perception into the antifungal mechanism of PiCB treatment in inhibiting P. digitatum growth through membrane peroxidation.

Penicillium italicum causes blue mold disease and leads to huge economic losses in citrus production. As a natural antifungal agent, clove essential oil (CEO), which is a generally recognized as safe (GRAS) substance, shows strong in vitro activity against fungal pathogens. However, few studies on CEO for controlling postharvest blue mold disease caused by P. italicum in citrus fruit have been reported. Our aims were to investigate the control efficacy and possible mechanisms involved of CEO against P. italicum. In the present study, CEO treatment inhibited the disease development of blue mold when applied at 0.05% to 0.8% (v/v), and with the effective concentration being obtained as 0.4% (v/v). Besides its direct antifungal activity, CEO treatment also spurred a rapid accumulation of H2O2 compared with untreated fruits, which might contribute to enhancing an increase in the activities of defense-related enzymes, such as β-1,3-glucanase (β-Glu), chitinase (CHI), phenylalanine ammonia-lyase (PAL), peroxidase (POD), polyphenol oxidase (PPO), and lipoxygenase (LOX) in citrus fruit. Results of real time-quantitative polymerase chain reaction (RT-qPCR) showed that the gene expressions of β-Glu, CHI, PAL, POD and PPO were up-regulated in CEO-treated fruits. At the same time, CEO treatment led to down-regulated expression of the LOX gene in citrus fruit. Clove essential oil effectively control the disease incidence of blue mold decay in citrus fruit by motivating the host-defense responses, suppressing the malondialdehyde (MDA) accumulation while enhancing the activities and gene expressions of defense-related enzymes. Our study provides an alternative preservative applying CEO to reduce postharvest fungal decay in citrus fruit.

Abstract Background Our study aims to evaluate the anti-growth effects of recombinant immunotoxin (IT) anti-c-Met/PE38KDEL on gastric cancer cells, and its mechnisms. Methods Gastric cancer cells were treated with increasing doses of IT and c-Met protein was quantified by Western blotting. Cell proliferation was determined by Cell Counting Kit-8 assay (CCK). [3H]-leucine incorporation assay was used to evaluate IT inhibition of protein synthesis. Cell apoptosis was quantified by flow cytometry. Caspase activities were measured using colorimetric protease assays. Results Cell growth and protein synthesis of the gastric cancer cell lines were suppressed by IT in a dose- and time-dependent manner. IT also induced apoptosis in a dose-dependent manner. The apoptosis rates of gastric cancer cell lines MKN-45 and SGC7901 were 19.19% and 27.37%, respectively when treated with 50 ng/ml of IT. There were significant increase ofcaspase-3 activity at 24 hr of IT treatment (100 ng/ml) (P < 0.01) in these gastric cancer cell lines. Conclusions IT anti-c-Met/PE38KDEL has anti-growth effects on the gastric cancer cell lines in vitro, and it provides an experimental basis for c-Met-targeted therapy towards in vivo testing.