Exploring the impact of high-altitude de-acclimatization on renal function: The roles of oxidative and endoplasmic reticulum stress in rat models.

BACKGROUND: High-altitude de-acclimatization (HADA) significantly impacts physiological functions when individuals acclimatize to high altitudes return to lower altitudes. This study investigates HADA's effects on renal function and structure in rats, focusing on oxidative and endoplasmic reticulum stress as potential mechanisms of renal injury. OBJECTIVE: To elucidate the pathophysiological mechanisms of renal damage in HADA and evaluate the efficacy of antioxidants Vitamin C (Vit C) and tauroursodeoxycholic acid (TUDCA) in mitigating these effects. METHODS: 88 male Sprague-Dawley rats were randomly divided into a control group, a high-altitude (HA) group, a high-altitude de-acclimatization (HADA) group, and a treatment group. The control group was housed in a sea level environment (500 m), while the HA, HADA, and treatment groups were placed in a simulated high-altitude chamber (5000 m) for 90 days. After this period, the HA group completed the modeling phase; the HADA group was further subdivided into four subgroups, each continuing to be housed in a sea level environment for 3, 7, 14, and 30 days, respectively. The treatment group was split into the Vit C group, the TUDCA group, and two placebo groups, receiving medication for 3 consecutive days, once daily upon return to the sea level. The Vit C group received 100 mg/kg Vit C solution via intravenous injection, the TUDCA group received 250 mg/kg TUDCA solution via intraperitoneal injection, and the placebo groups received an equivalent volume of saline similarly. Serum, urine, and kidney tissues were collected immediately after the modeling phase. Renal function and oxidative stress levels were assessed using biochemical and ELISA methods. Renal histopathology was observed with H&E, Masson's trichrome, PAS, and PASM staining. Transmission electron microscopy was used to examine the ultrastructure of glomeruli and filtration barrier. TUNEL staining assessed cortical apoptosis in the kidneys. Metabolomics was employed for differential metabolite screening and pathway enrichment analysis. RESULTS: Compared to the control and HA groups, the HADA 3-day group (HADA-3D) exhibited elevated renal function indicators, significant pathological damage, observable ultrastructural alterations including endoplasmic reticulum expansion and apoptosis. TUNEL-positive cells significantly increased, indicating heightened oxidative stress levels. Various differential metabolites were enriched in pathways related to oxidative and endoplasmic reticulum stress. Early intervention with Vit C and TUDCA markedly alleviated renal injury in HADA rats, significantly reducing the number of apoptotic cells, mitigating endoplasmic reticulum stress, and substantially lowering oxidative stress levels. CONCLUSION: This study elucidates the pivotal roles of oxidative and endoplasmic reticulum stress in the early-stage renal injury in rats undergoing HADA. Early intervention with the Vit C and TUDCA significantly mitigates renal damage caused by HADA. These findings provide insights into the pathophysiological mechanisms of HADA and suggest potential therapeutic strategies for its future management.

131I Induced In Vivo Proteolysis by Photoswitchable azoPROTAC Reinforces Internal Radiotherapy.

Photopharmacology, incorporating photoswitches such as azobenezes into drugs, is an emerging therapeutic method to realize spatiotemporal control of pharmacological activity by light. However, most photoswitchable molecules are triggered by UV light with limited tissue penetration, which greatly restricts the in vivo application. Here, this study proves that 131I can trigger the trans-cis photoisomerization of a reported azobenezen incorporating PROTACs (azoPROTAC). With the presence of 50 µCi mL-1 131I, the azoPROTAC can effectively down-regulate BRD4 and c-Myc levels in 4T1 cells at a similar level as it does under light irradiation (405 nm, 60 mW cm-2). What's more, the degradation of BRD4 can further benefit the 131I-based radiotherapy. The in vivo experiment proves that intratumoral co-adminstration of 131I (300 µCi) and azoPROTC (25 mg kg-1) via hydrogel not only successfully induce protein degradation in 4T1 tumor bearing-mice but also efficiently inhibit tumor growth with enhanced radiotherapeutic effect and anti-tumor immunological effect. This is the first time that a radioisotope is successfully used as a trigger in photopharmacology in a mouse model. It believes that this study will benefit photopharmacology in deep tissue.

Potential roles of the interactions between gut microbiota and metabolites in LPS-induced intrauterine inflammation (IUI) and associated preterm birth (PTB).

BACKGROUND: Prenatal exposure to intrauterine inflammation (IUI) is a crucial event in preterm birth (PTB) pathophysiology, increasing the incidence of neurodevelopmental disorders. Gut microbiota and metabolite profile alterations have been reported to be involved in PTB pathophysiology. METHOD AND RESULTS: In this study, IUI-exposed PTB mouse model was established and verified by PTB rate and other perinatal adverse reactions; LPS-indued IUI significantly increased the rates of PTB, apoptosis and inflammation in placenta tissue samples. LPS-induced IUI caused no significant differences in species richness and evenness but significantly altered the species abundance distribution. Non-targeted metabolomics analysis indicated that the metabolite profile of the preterm mice was altered, and differential metabolites were associated with signaling pathways including pyruvate metabolism. Furthermore, a significant positive correlation between Parasutterella excrementihominis and S4572761 (Nb-p-coumaroyltryptamine) and Mreference-1264 (pyruvic acid), respectively, was observed. Lastly, pyruvic acid treatment partially improved LPS-induced IUI phenotypes and decreased PTB rates and decreased the apoptosis and inflammation in placenta tissue samples. CONCLUSION: This study revealed an association among gut microbiota dysbiosis, metabolite profile alterations, and LPS-induced IUI and PTB in mice models. Our investigation revealed the possible involvement of gut microbiota in the pathophysiology of LPS-induced IUI and PTB, which might be mediated by metabolites such as pyruvic acid. Future studies should be conducted to verify the findings through larger sample-sized animal studies and clinical investigations.

Phytophthora RxLR effector PcSnel4B promotes degradation of resistance protein AtRPS2.

Phytophthora capsici deploys effector proteins to manipulate host immunity and facilitate its colonization. However, the underlying mechanisms remain largely unclear. In this study, we demonstrated that a Sne-like (Snel) RxLR effector gene PcSnel4 is highly expressed at the early stages of P. capsici infection in Nicotiana benthamiana. Knocking out both alleles of PcSnel4 attenuated the virulence of P. capsici, while expression of PcSnel4 promoted its colonization in N. benthamiana. PcSnel4B could suppress the hypersensitive reaction (HR) induced by Avr3a-R3a and RESISTANCE TO PSEUDOMONAS SYRINGAE 2 (AtRPS2), but it did not suppress cell death elicited by Phytophthora infestin 1 (INF1) and Crinkler 4 (CRN4). COP9 signalosome 5 (CSN5) in N. benthamiana was identified as a host target of PcSnel4. Silencing NbCSN5 compromised the cell death induced by AtRPS2. PcSnel4B impaired the interaction and colocalization of Cullin1 (CUL1) and CSN5 in vivo. Expression of AtCUL1 promoted the degradation of AtRPS2 and disrupted HR, while AtCSN5a stabilized AtRPS2 and promoted HR, regardless of the expression of AtCUL1. PcSnel4 counteracted the effect of AtCSN5 and enhanced the degradation of AtRPS2, resulting in HR suppression. This study deciphered the underlying mechanism of PcSnel4-mediated suppression of HR induced by AtRPS2.

Sensitivity analysis and point mutations in BcSDHB confer cyclobutrifluram resistance in Botrytis cinerea from China.

Botrytis cinerea is one of the most destructive pathogens worldwide. It can damage over 200 crops, resulting in significant yield and quality losses. Cyclobutrifluram, a new generation of succinate dehydrogenase inhibitors, exhibits excellent inhibitory activity against B. cinerea. However, the baseline sensitivity and resistance of B. cinerea to cyclobutrifluram remains poorly understood. This study was designed to monitor the sensitivity frequency distribution, assess the resistance risk, and clarify the resistance mechanism of B. cinerea to cyclobutrifluram. The baseline sensitivity of B. cinerea isolates to cyclobutrifluram was 0.89 µg/mL. Cyclobutrifluram-resistant B. cinerea populations are present in the field. Six resistant B. cinerea isolates investigated in this study possessed enhanced compound fitness index compared to the sensitive isolates according to mycelial growth, mycelial dry weight, conidiation, conidial germination rate, and pathogenicity. Cyclobutrifluram exhibited no cross-resistance with tebuconazole, fludioxonil, cyprodinil, or iprodione. Sequence alignment revealed that BcSDHB from cyclobutrifluram-resistant B. cinerea isolates had three single substitutions (P225F, N230I, or H272R). Molecular docking verified that these mutations in BcSDHB conferred cyclobutrifluram resistance in B. cinerea. In conclusion, the resistance risk of B. cinerea to cyclobutrifluram is high, and the point mutations in BcSDHB (P225F, N230I, or H272R) confer cyclobutrifluram resistance in B. cinerea. This study provided important insights into cyclobutrifluram resistance in B. cinerea and offered valuable information for monitoring and managing cyclobutrifluram resistance in the future.

Pseudogene CLEC4GP1 modulates trophoblast cell apoptosis and invasion via IL-15 inhibition.

Preeclampsia (PE) is a pregnancy-associated complication accompanied by gestational hypertension and proteinuria, affecting 2-8% of pregnancies globally. The placental trophoblast cell invasion of decidua and myometrium during early gestation is crucial for healthy placentation. Thus, trophoblast dysfunction might contribute to PE onset. Therefore, further investigations are needed to elucidate the underlying mechanism of trophoblast cell functions. In the present study, we identified a novel pseudogene named C-Type Lectin Domain Family 4 Member G Pseudogene 1 (CLEC4GP1), which was aberrantly expressed in PE placental tissues. In vitro analyses showed that CLEC4GP1 overexpression significantly increased the cell viability and invasiveness and decreased the apoptosis rate of HTR-8/SVneo and JEG-3 cells, while CLEC4GP1 knockdown exerted opposite effects, suggesting the beneficial role of CLEC4GP1 in trophoblast cells. Next, co-expression analysis found that CLEC4GP1 was negatively correlated with Interleukin 15 (IL-15). The expression of IL-15 dramatically increased in PE placental tissues. In HTR-8/SVneo and JEG-3 cells, IL-15 exhibited detrimental effects, opposite to CLEC4GP1, and they were negatively correlated. In addition, CLEC4GP1 attenuates the mRNA stability of IL-16 by inhibiting the binding between human antigen R (HuR) protein and IL-15 RNA. Finally, the obverse effects of CLEC4GP1 and IL-15 were investigated, and results showed that IL-15 reverted CLEC4GP1 induced cellular functions. In brief, these data suggest that CLEC4GP1/IL-15 axis might modulate the occurrence and progression of PE via influencing the trophoblast cell viability, apoptosis, and invasive capability. This study provided cognizance of targeting the CLEC4GP1/IL-15 axis as a novel therapeutic approach to mitigate PE progression.

Containing anti-PLA2R IgG antibody induces podocyte injury in idiopathic membranous nephropathy.

Background: Idiopathic membranous nephropathy is widely recognized as an autoimmune kidney disease that is accompanied by the discovery of several autoantibodies, and the antibody subclass in the circulation of patients with iMN is mainly IgG. However, the direct pathogenic effect of the containing anti-PLA2R IgG antibody on podocytes is not clear.Method: A protein G affinity chromatography column was used to purify serum IgG antibodies. Containing anti-PLA2R IgG antibodies from iMN patients and IgG from healthy controls were also obtained. Based on the established in vitro podocyte culture system, purified IgG antibodies from the two groups were used to stimulate podocytes, and the expression of essential podocyte proteins (podocin), the levels of inflammatory cytokines in the cell supernatant, cytoskeletal disorders, and podocyte apoptosis were analyzed.Results: Compared with that in the normal IgG group, the expression of podocin and podocin mRNA was reduced (p = 0.016 and p = 0.005, respectively), the fluorescence intensity of podocin on the surface of podocytes was reduced, the cytoskeleton of podocytes was disordered and reorganized, and the ratio of podocyte apoptosis was increased in the iMN group (p = 0.008).Conclusion: The containing anti-PLA2R IgG antibody might have a direct damaging effect on podocytes in idiopathic membranous nephropathy.

The effects of music therapy on peripherally inserted central catheter in hospitalized children with leukemia.

To explore the effect of music therapy on children with leukemia who have peripherally inserted central catheters (PICC).In this study, we divided 107 patients undergoing PICC into music group (47 cases) and control group (60 cases). The music group received music therapy during PICC, while the control group was given no complementary treatment. The total length of catheterization, the use of sedatives and the changes of pain level and emotion level before and after PICC placement were compared between two groups.Compared with the control group, the total PICC placement time of the music group was significantly shorter (35(30-40) vs. 60(60-60); Z = -8.307; p < 0.001), and the use of sedative medications was also significantly reduced (4.35% (n = 2) vs. 91.84% (n = 45); p < 0.001). Moreover, the pain of catheterization was significantly alleviated. The median difference of pain scores of the music group was significantly less (2(1-3) vs. 5(5-5); p < 0.001). The mood of patients was also improved. The median difference of emotional scores of the music group was significantly more (5(4.75-6) vs. 3(3-3); p < 0.001) than the control group.Music therapy is effective to use in PICC. It can shorten the treatment time, reduce the use of sedative medications, and improve the children's emotion and pain response significantly, which is worth clinical application.

Prediction of ADMET Properties of Anti-Breast Cancer Compounds Using Three Machine Learning Algorithms.

In recent years, machine learning methods have been applied successfully in many fields. In this paper, three machine learning algorithms, including partial least squares-discriminant analysis (PLS-DA), adaptive boosting (AdaBoost), and light gradient boosting machine (LGBM), were applied to establish models for predicting the Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET for short) properties, namely Caco-2, CYP3A4, hERG, HOB, MN of anti-breast cancer compounds. To the best of our knowledge, the LGBM algorithm was applied to classify the ADMET property of anti-breast cancer compounds for the first time. We evaluated the established models in the prediction set using accuracy, precision, recall, and F1-score. Compared with the performance of the models established using the three algorithms, the LGBM yielded most satisfactory results (accuracy > 0.87, precision > 0.72, recall > 0.73, and F1-score > 0.73). According to the obtained results, it can be inferred that LGBM can establish reliable models to predict the molecular ADMET properties and provide a useful tool for virtual screening and drug design researchers.

The impact of COVID-19 on maritime pilots: Evidence and lessons.

The COVID-19 pandemic led to port congestion and disruption to global logistics and supply chains. While previous research has examined the impact on port performance and economics, social issues, such as the impact on port personnel (including pilots), have been overlooked. In this context, this paper examines the challenges experienced by Chinese pilots during the pandemic through in-depth interviews with 28 pilots. It shows that the draconian pandemic control measures adopted in China, rather than the pandemic itself, impaired pilots' physical and mental health, reduced their availability, and introduced new safety hazards, which curtailed both the port's capacity and ability to provide efficient and safe pilotage and resulted in sub-standard services. The findings suggest that there is a serious issue regarding the absence of effective mechanisms for pilots to raise their health and safety concerns and how these might be addressed by port administrators and/or local authorities. Worker participation and involvement in occupational health and safety management was problematic. These findings have implications for pilot station management at both company and government administrative and legislative levels.

Fatigue during the COVID-19 pandemic: The experiences of Chinese seafarers.

Though the COVID-19 pandemic is drawing to a close, very little is known about the impact of China's zero-COVID policy on Chinese seafarers. This paper examines Chinese seafarers' experiences of fatigue during the pandemic. It adopted a mix-method research design involving two quantitative surveys conducted with seafarers before and during the pandemic and 35 in-depth interviews with both seafarers and managers. All the participants were from two Chinese shipping companies. The comparisons between the two surveys show that Chinese seafarers experienced significantly higher levels of fatigue during the pandemic. The interview data suggest a range of factors underpinning the higher levels of fatigue including fear of being infected, increased workload, wearing of four-piece personal protection equipment (PPE), the deprivation of shore leaves, and the prolonged service time. More importantly, the data indicate that the draconian zero-COVID policy in China and the related policy guidelines for Chinese shipping companies and seafarers reinforce these factors. This research extends previous research by providing an exclusive and comprehensive examination of seafarer fatigue during the pandemic and revealing that the policies adopted by seafarers' home countries can have profound implications for seafarers' experiences of fatigue. Suggestions are provided at the end of the paper.

Fatigue at sea during and after the COVID-19 pandemic: A comparative study of two matched samples of seafarers.

This paper examines seafarers' experience of fatigue during and after the pandemic. A multi-phase mixed methods research design was used, including two quantitative surveys (Nduring-pandemic=501 and Nafter-pandemic=412) and 36 in-depth interviews. Applying propensity score matching the two samples to approximate the conditions of a randomized controlled experiment, the study shows that surprisingly seafarers reported higher levels of fatigue after the pandemic. Qualitative interviews with seafarers and ship managers reveal the underlying reason - the intensified ship inspection regime together with policy and regulatory updates/revisions in the immediate aftermath of the pandemic increased seafarers' workload and made seafarers more fatigued. The results of the two surveys also show that while fatigue risk factors differed between the two periods, fatigue risk can be managed and mitigated in both periods by implementing fatigue risk management policies and practices. Policy and management implications for improving seafarers' occupational health and safety are discussed at the end of the paper.

Pathological Analysis of Vascularization of the Arterialized Veins in Failed Arteriovenous Fistulae.

PURPOSE: To assess venous wall vascularization and its correlation with neointimal hyperplasia (NIH) in failed arteriovenous fistulae (AVFs). MATERIALS AND METHODS: A total of 43 uremic patients who underwent de novo AVF creation and 39 patients who underwent reconstruction of failed fistulae were enrolled in the study. A 5-10-mm vein segment adjacent to the future fistula creation or reconstruction site was surgically removed and assessed using histopathological analyses and stained by immunohistochemistry to quantify vasa vasorum density (VVD). RESULTS: Both the intimal thickness (70.68 [28.81-99.54] vs 4.53 [2.69-7.30] µm, P < .001) and the intimal thickness-to-medial thickness ratio (2.20 [0.77-4.36] vs 0.15 [0.10-0.30], P < .001) were higher in failed AVFs than in preaccess veins. CD31- and factor VIII-marked VVDs in both the intima (6.31 [1.62-12.53] vs 0.0 [0.0-0.0], P < .001; 7.82 [3.33-11.61] vs 0.0 [0.0-0.0], P < .001) and media (10.0 [7.59-12.95] vs 3.71 [2.44-4.87], P < .001; 8.33 [5.55-13.0] vs 3.57 [2.53-4.82], P < .001) as well as the intimal VVD:medial VVD ratio (0.67 [0.19-1.08] vs 0.0 [0.0-0.0], P < .001; 0.71 [0.39-1.14] vs 0.0 [0.0-0.0], P < .001) were significantly higher in failed AVFs than in preaccess veins. Moreover, there was a positive relationship between the intimal VVD:medial VVD ratio and the intimal thickness:medial thickness ratio (P < .001). In addition, the vascular endothelial cell growth factor A expression was higher in failed AVFs than in preaccess veins. CONCLUSIONS: Vascularization of the vessel wall was noticeably more developed in the arterialized veins, especially at the NIH regions in failed AVFs.

Identifying the neural basis for rosacea using positron emission tomography-computed tomography cerebral functional imaging analysis: A cross-sectional study.

BACKGROUND: The neural basis of rosacea is not well understood. This study aimed to determine whether cerebral glucose metabolism (CGM) changes on 18 F-fluorodeoxyglucose (18 F-FDG) positron emission tomography (PET)/computed tomography (CT) scans can detect functional network changes in specific brain areas in patients with rosacea. MATERIALS AND METHODS: Eight adults with rosacea and 10 age/sex-matched healthy adults (controls) were enrolled in the study. 18 F-FDG PET/CT brain images for all eight patients and whole-body images for two of the patients were analyzed qualitatively and semi-quantitatively. Differences between the study groups were examined using Fischer's exact test and a Student's t-test. A voxel-based analysis using statistical parametric mapping was performed to compare the brain metabolism of the patients with that of the controls. RESULTS: Compared with the controls, the patients with rosacea showed extensive changes in the CGM signals in the cerebral cortex and limbic system, with less CGM shown in the right superior parietal lobule, right postcentral gyrus, right parahippocampal gyrus, left superior frontal gyrus, and lateral posterior thalamic nucleus and more CGM in the right precentral gyrus, left inferior frontal gyrus, and cerebellar tonsil. No dysmetabolic lesions were found in the whole-body 18 F-FDG PET/CT images. CONCLUSION: Specific neural functional changes occur in patients with rosacea that may explain its pathogenesis.

The impact of 2008 financial crisis and COVID-19 pandemic on the demand and supply of seafarer officers: Evidence from China.

During the shipping market boom in the 2000s, China adopted initiatives to expand its maritime education and training (MET) capacity, which significantly increased the supply of seafarer officers in the next few years. Drawing on multiple types of statistical information, including MET enrolments, seafarer numbers, seafarer wages, and labour market analyses, this paper examines the outcomes of the initiatives in the aftermath of the 2008 financial crisis and the COVID-19 outbreak. It shows that the financial crisis together with the expanded training capacity led to a serious oversupply problem, characterised by a lack of job opportunities, depressed wages, and slow career progression for junior officers. When the situation improved in 2017, however, a shortage of junior officers ensued, and their number plummeted quickly. The recent COVID-19 pandemic increased the demand for Chinese officers. Nevertheless, the decline in the number of 3rd officers continued. This paper discusses the causes and policy implications of the quick reverse from an oversupply to an acute shortage.

Seafarers' mental health during the COVID-19 pandemic: An examination of current supportive measures and their perceived effectiveness.

As the current COVID-19 pandemic and the resulting crew change crisis exacerbates the mental health problem faced by seafarers, various maritime stakeholders have mobilised their resources and strengths to provide a variety of supportive measures to address the issue. This paper aims to find out what measures have been adopted in the industry and how widely they have been experienced/received by seafarers and evaluate their effectiveness. To achieve this aim, this research employed a mixed methods design involving qualitative interviews with 26 stakeholders and a quantitative questionnaire survey of 817 seafarers. The research identified a total number of 22 mental health support measures, all of which were perceived to have contributed positively to seafarers' mental health. However, not all of them were widely available to or utilised by seafarers. The findings also highlighted the importance of family, colleagues, shipping companies, and government agencies, as they are associated with the most effective support measures, namely communication with family, timely crew changes, being prioritised for vaccination, being vaccinated, and a positive and collegial atmosphere on-board. Based on the findings, recommendations are provided.

Comparisons of different exercise interventions on glycemic control and insulin resistance in prediabetes: a network meta-analysis.

BACKGROUND: In order to recommend the optimal type of exercise for type 2 diabetes prevention, different exercise interventions were compared with respect to their effects on glycemic control and insulin resistance. METHODS: Studies on the curative effect of aerobic exercise training (AET), resistance training (RT), or control training (CT) on prediabetes were retrieved from the PubMed, Embase, SPORTDiscus, and Cochrane Library databases. Body mass index (BMI); homeostasis model assessment of insulin resistance index (HOMA-IR); and fasting blood glucose (FBG), glycated hemoglobin (HbA1c), and insulin levels were used as outcome indicators. The Q statistic was calculated to evaluate heterogeneity within studies. A fixed- or random-effects model was used for pooling data based on nonsignificant or significant heterogeneities. A consistency test was conducted using a node-splitting analysis. RESULTS: A total of 13 eligible studies were included. The results of the direct meta-analysis indicated that AET or RT could significantly reduce the HbA1c level in prediabetic individuals compared to CT [AET vs. CT: standardized mean difference (SMD) = - 0.6739, 95% confidence interval (CI) = - 0.9424 to - 0.4055 to RT vs. CT: SMD = - 1.0014, 95% CI = - 1.3582 to - 0.6446]. The findings from the network meta-analysis showed that there were no statistical differences among the four comparisons for all the indicators except for lower HbA1c level (SMD = - 0.75, 95% CI = - 1.31 to - 0.19) and HOMA-IR (SMD = - 1.03, 95% CI = - 1.96 to - 0.10) in the AET group than in the CT group. In addition, prediabetic individuals in the AET + RT group showed greater control of BMI and insulin and FBG levels than those in the other groups, whereas AET was the most effective in controlling HbA1c and HOMA-IR levels in prediabetic individuals. CONCLUSION: AET, AET + RT, and RT exerted beneficial effects on insulin resistance and glycemic control in prediabetic patients. From the existing data, AET or AET + RT is preferentially recommended for these patients, although further studies may unveil RT as a promising therapy. Benefits from all types of exercise seem to occur in an intensity-dependent manner.

MicroRNAs in acute pancreatitis: From pathogenesis to novel diagnosis and therapy.

Acute pancreatitis (AP) is an inflammatory disorder initiated by activation of pancreatic zymogens, leading to pancreatic injury and systemic inflammatory response. MicroRNAs (miRNAs) have emerged as important regulators of gene expression and key players in human physiological and pathological processes. Discoveries over the past decade have confirmed that altered expression of miRNAs is implicated in the pathogenesis of AP. Indeed, a number of miRNAs have been found to be dysregulated in various cell types involved in AP such as acinar cells, macrophages, and lymphocytes. These aberrant miRNAs can regulate acinar cell necrosis and apoptosis, local and systemic inflammatory response, thereby contributing to the initiation and progression of AP. Moreover, patients with AP possess unique miRNA signatures when compared with healthy individuals or those with other diseases. In view of their stability and easy detection, therefore, miRNAs have the potential to act as biomarkers for the diagnosis and assessment of patients with AP. In this review, we provide an overview of the novel cellular and molecular mechanisms underlying the roles of miRNAs during the disease processes of AP, as well as the potential diagnosis and therapeutic biomarkers of miRNAs in patients with AP.

Abdominal paracentesis drainage attenuates severe acute pancreatitis by enhancing cell apoptosis via PI3K/AKT signaling pathway.

Our previous studies have shown that abdominal paracentesis drainage (APD) is a safe and effective strategy for patients with severe acute pancreatitis (SAP). However, the underlying mechanisms behind APD treatment remain poorly understood. Given that apoptosis is a critical pathological response of SAP, we here aim to investigate the effect of APD on cell apoptosis in pancreatic tissues during SAP and to explore its potential molecular mechanism. SAP was induced by 5% sodium-taurocholate retrograde while APD group was inserted a drainage tube into the right lower abdomen of rats immediately after SAP induction. Histopathological staining, serum amylase, endotoxin and inflammatory mediators were measured. Cell apoptosis, apoptosis-related proteins and signaling pathway were also evaluated. Our results demonstrated that APD treatment significantly attenuated pancreatic damage and decreased the serum levels of amylase, endotoxin, TNF-α, IL-1 and IL-6 in rats with SAP. Notably, APD treatment enhanced cell apoptosis and reduced necrosis in pancreatic tissues, as evidenced by Tunnel staining, the increased pro-apoptosis proteins (Cleaved-caspase-3 and bax) and decreased anti-apoptosis protein (Bcl-2). Moreover, the effect of APD on cell apoptosis was further confirmed by the regulatory pathway of PI3K/AKT and NF-kB signaling pathway. These results suggest that APD attenuates the severity of SAP by enhancing cell apoptosis via suppressing PI3K/AKT signaling pathway. Our findings provide new insights for understanding the effectiveness of APD in patients with SAP.

Determination of the Oxidative Stability of Camellia Oils Using a Chemometrics Tool Based on 1H NMR Spectra and α-Tocopherol Content.

This study, for the first time, predicts oxidative stability in camellia oils by partial least squares (PLS) built with proton nuclear magnetic resonance (1H NMR) and α-tocopherol content. The prediction models were established by the PLS method. Outlier detection, latent variables optimization, data pretreatment, and important variables selection were applied for models optimization. All the developed models exhibited good performance as indicated by R2 > 0.895 and root mean square error of estimation and root mean square error of prediction less than 0.322 and 0.307. For verification of the contribution of 1H NMR spectra and α-tocopherol for prediction performance, a PLS model with fatty acids composition instead of 1H NMR spectra and one with only 1H NMR spectra as input variables were developed, respectively. The results showed that the model based on 1H NMR data was more accurate and precise than that based on fatty acid composition data. And the performance of the models was significantly degraded without α-tocopherol as input variables.