Secondary metabolites in host pears defense against two fruit borers and cytochrome-P450-mediated counter-defense.

Herbivorous insects have evolved metabolic strategies to survive the challenges posed by plant secondary metabolites (SMs). This study reports an exploration of SMs present in pears, which serve as a defense against invasive Cydia pomonella and native Grapholita molesta and their counter-defense response. The feeding preferences of fruit borers are influenced by the softening of two pear varieties as they ripen. The content of SMs, such as quercetin and rutin, increases due to feeding by fruit borers. Notably, quercetin levels only increase after C. pomonella feeding. The consumption of SMs affects the growth of fruit borer population differently, potentially due to the activation of P450 genes by SMs. These two fruit borers are equipped with specific P450 enzymes that specialize in metabolizing quercetin and rutin, enabling them to adapt to these SMs in their host fruits. These findings provide valuable insights into the coevolution of plants and herbivorous insects.

Targeting deubiquitinase OTUB1 protects vascular smooth muscle cells in atherosclerosis by modulating PDGFRß.

Atherosclerosis is a chronic artery disease that causes various types of cardiovascular dysfunction. Vascular smooth muscle cells (VSMCs), the main components of atherosclerotic plaque, switch from contractile to synthetic phenotypes during atherogenesis. Ubiquitylation is crucial in regulating VSMC phenotypes in atherosclerosis, and it can be reversely regulated by deubiquitinases. However, the specific effects of deubiquitinases on atherosclerosis have not been thoroughly elucidated. In this study, RNAi screening in human aortic smooth muscle cells was performed to explore the effects of OTU family deubiquitinases, which revealed that silencing OTUB1 inhibited PDGF-BB-stimulated VSMC phenotype switch. Further in vivo studies using Apoe-/- mice revealed that knockdown of OTUB1 in VSMCs alleviated atherosclerosis plaque burden in the advanced stage and led to a stable plaque phenotype. Moreover, VSMC proliferation and migration upon PDGF-BB stimulation could be inhibited by silencing OTUB1 in vitro. Unbiased RNA-sequencing data indicated that knocking down OTUB1 influenced VSMC differentiation, adhesion, and proliferation. Mass spectrometry of ubiquitinated protein confirmed that proteins related to cell growth and migration were differentially ubiquitylated. Mechanistically, we found that OTUB1 recognized the K707 residue ubiquitylation of PDGFRß with its catalytic triad, thereby reducing the K48-linked ubiquitylation of PDGFRß. Inhibiting OTUB1 in VSMCs could promote PDGFRß degradation via the ubiquitin-proteasome pathway, so it was beneficial in preventing VSMCs' phenotype switch. These findings revealed that knocking down OTUB1 ameliorated VSMCs' phenotype switch and atherosclerosis progression, indicating that OTUB1 could be a valuable translational therapeutic target in the future.

Vitamin D status, vitamin D receptor polymorphisms, and risk of type 2 diabetes: A prospective cohort study.

CONTEXT: Vitamin D status has been associated with risk of type 2 diabetes (T2D), but evidence is scarce regarding whether such relation differs by glycemic status. OBJECTIVE: To prospectively investigate the association between serum 25-hydroxyvitamin D [25(OH)D] and risk of incident T2D across the glycemic spectrum and the modification effect of genetic variants in vitamin D receptor (VDR). METHODS: This prospective study included 379,699 participants without T2D at baseline from the UK Biobank. Analyses were performed according to glycemic status and HbA1c levels. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs. RESULTS: During a median of 14.1 years of follow-up, 6,315 participants with normoglycemia and 9,085 prediabetes patients developed T2D. Compared to individuals with 25(OH)D <25 nmol/L, the multivariable-adjusted hazard ratios (95% CIs) of incident T2D for those with 25(OH)D ≥75 nmol/L was 0.62 (0.56, 0.70) among the normoglycemia and 0.64 (0.58, 0.70) among the prediabetes. A significant interaction was observed between 25(OH)D and VDR polymorphisms among participants with prediabetes (Pinteraction=0.017), whereby the reduced HR of T2D associated with higher 25(OH)D was more prominent in those carrying T allele of rs1544410. Triglycerides levels mediated 26% and 34% of the association between serum 25(OH)D and incident T2D among participants with normoglycemia and prediabetes. CONCLUSIONS: Higher serum 25(OH)D concentrations were associated with lower T2D risk across the glycemic spectrum below the threshold for diabetes, and the relations in prediabetes were modified by VDR polymorphisms. Improving lipid profile, mainly triglycerides, accounted for part of the favorable associations.

MH-STRALP: A scoring system for prognostication in patients with upper gastrointestinal bleeding.

BACKGROUND: Upper gastrointestinal bleeding (UGIB) is a common medical emergency and early assessment of its outcomes is vital for treatment decisions. AIM: To develop a new scoring system to predict its prognosis. METHODS: In this retrospective study, 692 patients with UGIB were enrolled from two centers and divided into a training (n = 591) and a validation cohort (n = 101). The clinical data were collected to develop new prognostic prediction models. The endpoint was compound outcome defined as (1) demand for emergency surgery or vascular intervention, (2) being transferred to the intensive care unit, or (3) death during hospitalization. The models' predictive ability was compared with previously established scores by receiver operating characteristic (ROC) curves. RESULTS: Totally 22.2% (131/591) patients in the training cohort and 22.8% (23/101) in the validation cohort presented poor outcomes. Based on the stepwise-forward Logistic regression analysis, eight predictors were integrated to determine a new post-endoscopic prognostic scoring system (MH-STRALP); a nomogram was determined to present the model. Compared with the previous scores (GBS, Rockall, ABC, AIMS65, and PNED score), MH-STRALP showed the best prognostic prediction ability with area under the ROC curves (AUROCs) of 0.899 and 0.826 in the training and validation cohorts, respectively. According to the calibration curve, decision curve analysis, and internal cross-validation, the nomogram showed good calibration ability and net clinical benefit in both cohorts. After removing the endoscopic indicators, the pre-endoscopic model (pre-MH-STRALP score) was conducted. Similarly, the pre-MH-STRALP score showed better predictive value (AUROCs of 0.868 and 0.767 in the training and validation cohorts, respectively) than the other pre-endoscopic scores. CONCLUSION: The MH-STRALP score and pre-MH-STRALP score are simple, convenient, and accurate tools for prognosis prediction of UGIB, and may be applied for early decision on its management strategies.

A review of obstructive sleep apnea and lung cancer: epidemiology, pathogenesis, and therapeutic options.

Despite undeniable advances in modern medicine, lung cancer still has high morbidity and mortality rates. Lung cancer is preventable and treatable, and it is important to identify new risk factors for lung cancer, especially those that can be treated or reversed. Obstructive sleep apnea (OSA) is a very common sleep-breathing disorder that is grossly underestimated in clinical practice. It can cause, exacerbate, and worsen adverse outcomes, including death and various diseases, but its relationship with lung cancer is unclear. A possible causal relationship between OSA and the onset and progression of lung cancer has been established biologically. The pathophysiological processes associated with OSA, such as sleep fragmentation, intermittent hypoxia, and increased sympathetic nervous excitation, may affect normal neuroendocrine regulation, impair immune function (especially innate and cellular immunity), and ultimately contribute to the occurrence of lung cancer, accelerate progression, and induce treatment resistance. OSA may be a contributor to but a preventable cause of the progression of lung cancer. However, whether this effect exists independently of other risk factors is unclear. Therefore, by reviewing the literature on the epidemiology, pathogenesis, and treatment of lung cancer and OSA, we hope to understand the relationships between the two and promote the interdisciplinary exchange of ideas between basic medicine, clinical medicine, respiratory medicine, sleep medicine, and oncology.

Analysis of risk factors related to the progression rate of hemifacial spasm.

Introduction: Although there have been many researches on the etiology and risk factors with the onset of hemifacial spasm, researches on the risk factors related to progression rate are limited. This study aims to analyze the risk factors related to the progression rate of hemifacial spasm. Methods: The study enrolled 142 patients who underwent microvascular decompression for hemifacial spasm. Based on the duration and severity of symptoms, patients were classified into rapid progression group and slow progression group. To analyze risk factors, univariate and multivariate logistic regression analyses were conducted. Of 142 patients with hemifacial spasm, 90(63.3%) were classified as rapid progression group, 52(36.7%) were classified as slow progression group. Results: In the univariate analysis, there were significant statistical differences between the two groups in terms of age of onset (P = 0.021), facial nerve angle (P < 0.01), hypertension (P = 0.01), presence of APOE ε4 expression (P < 0.01) and different degrees of brainstem compression in the Root Entry Zone (P < 0.01). In the multivariable analyses, there were significant statistical differences between the two groups in terms of age of symptom onset (P < 0.01 OR = 6.591), APOE ε4 (P < 0.01 OR = 5.691), brainstem compression (P = 0.006 OR = 5.620), and facial nerve angle (P < 0.01 OR = 5.758). Furthermore, we found no significant correlation between the severity of facial spasms and the progression rate of the disease (t = 2.47, P = 0.12>0.05). Conclusion: According to our study, patients with facial nerve angle ≤ 96.5°, severer compression of the brainstem by offending vessels, an onset age > 45 years and positive expression of APOE ε4, may experience faster progression of hemifacial spasm.

Study on the affinity sites of cadmium's binding to ligands by thermodynamics and nuclear magnetic resonance spectroscopy.

The affinity sites of cadmium (Cd(II)) when binding to cysteine (Cys) and glutathione (GSH) were studied via thermodynamics and nuclear magnetic resonance (NMR) spectroscopy methods. The results showed that the Cd(II) binding sites of Cys and GSH were -SH (exothermic), -NH2 (endothermic) and -COOH (endothermic). The thermodynamic behaviour of Cd(II) binding to Cys/GSH in boric acid and HEPES buffers differed, with the former being mainly endothermic and the latter mainly exothermic. It could be inferred that, in the boric acid system, the main binding site of Cd(II) with Cys and GSH is changed from -SH in HEPES to -COOH and -NH2 in boric acid. This was confirmed by the results of NMR experiments of Cd(II) with Cys/GSH. 1D 1H-NMR experiments showed that, after the combination of Cd(II) and Cys, the changes in the chemical shifts and peak strengths of protons near the -SH group for the reaction in HEPES were greater than when boric acid buffer was used. Changes in the chemical shift and peak strength of the -NH2 protons due to the binding of Cd(II) to GSH were evident in the boric acid buffer but not in HEPES. The screening of functional monomers is very important in the process of preparation of cadmium ion-imprinted materials. This research provides important theoretical and experimental guidance for the screening of functional monomers.

Tumor-associated macrophages affect the treatment of lung cancer.

As one of the most common malignant tumors in the world, lung cancer has limited benefits for patients despite its diverse treatment methods due to factors such as personalized medicine targeting histological type, immune checkpoint expression, and driver gene mutations. The high mortality rate of lung cancer is partly due to the immune-suppressive which limits the effectiveness of anti-cancer drugs and induces tumor cell resistance. The currently widely recognized TAM phenotypes include the anti-tumor M1 and pro-tumor M2 phenotypes. M2 macrophages promote the formation of an immune-suppressive microenvironment and hinder immune cell infiltration, thereby inhibiting activation of the anti-tumor immune system and aiding tumor cells in resisting treatment. Analyzing the relationship between different treatment methods and macrophages in the TME can help us better understand the impact of TAMs on lung cancer and confirm the feasibility of targeted TAM therapy. Targeting TAMs to reduce the M2/M1 ratio and reverse the immune-suppressive microenvironment can improve the clinical efficacy of conventional treatment methods and potentially open up more efficient combination treatment strategies, maximizing the benefit for lung cancer patients.

Whole transcriptome sequencing reveals key genes and ceRNA regulatory networks associated with pimpled eggs in hens.

Eggshell is one of the most important indicators of egg quality, and due to low shell strength, pimple eggs (PE) are more susceptible to breakage, thus causing huge economic losses to the egg industry. At the current time, the molecular mechanisms that regulate the formation of pimple eggs are poorly understood. In this study, uterine tissues of PE-laying hens (n = 8) and normal egg (NE) -laying hens (n = 8) were analyzed by whole transcriptome sequencing, and a total of 619 differentially expressed mRNAs (DE mRNAs), 122 differentially expressed lncRNAs (DE lncRNAs) and 21 differentially expressed miRNAs (DE miRNAs) were obtained. Based on the targeting relationship among DE mRNAs, DE lncRNAs and DE miRNAs, we constructed a competitive endogenous RNA (ceRNA) network including 12 DE miRNAs, 19 DE lncRNAs, and 128 DE mRNAs. Considering the large amount of information contained in the network, we constructed a smaller ceRNA network to better understand the complex mechanisms of pimple egg formation. The smaller ceRNA network network contains 7 DE lncRNAs (LOC107056551, LOC121109367, LOC121108909, LOC121108862, LOC112530033, LOC121113165, LOC107054145), 5 DE miRNAs (gga-miR-6568-3p, gga-miR-31-5p, gga-miR-18b-3p, gga-miR-1759-3p, gga-miR-12240-3p) and 7 DE mRNAs (CABP1, DNAJC5, HCN3, HPCA, IBSP, KCNT1, OTOP3), and these differentially expressed genes may play key regulatory roles in the formation of pimpled eggs in hens. This study provides the overall expression profiles of mRNAs, lncRNAs and miRNAs in the uterine tissues of hens, which provides a theoretical basis for further research on the molecular mechanisms of pimpled egg formation, and has potential applications in improving eggshell quality.

Developing cellulose-based hydrophobic/hydrophilic composites for efficient adsorption of oils and heavy metals from water.

The oily wastewater and heavy metal ions have been increasingly discharged into water environment, posting a serious threat to ecosystems and human health. However, it remains challenging to use single separation technology to effectively remove oil and heavy metal ions in oil-water mixtures simultaneously. Herein, novel hydrophobic/hydrophilic composites (HHC) were successfully prepared by using A4 paper-derived hydrophilic cellulose as the modified matrix, modifying the polydopamine layer and in-situ growth nanoscale zero-valent iron as active adsorption materials, combined with oleic acid-modified hydrophobic magnetic hollow carbon microspheres, which were used to efficiently and rapidly adsorb heavy metals and oil in oil-water mixtures. Under the optimal adsorption conditions, the adsorption amounts of As(III), As(V), Pb(II) and Cu(II) were 289.6 mg/g, 341.9 mg/g, 241.2 mg/g and 277.5 mg/g, respectively, and the mass transfer rate of HHC to the target ions is fast. The HHC have efficient separation performance for layered oil-water mixtures and emulsified oil-water mixtures, with separation efficiency of 97 % and 92 %. At the same time, due to the abundant adsorption sites, the HHC also exhibit splendid regeneration performance for the four ions after multiple adsorption utilization. Our work designed a approach to achieving promising oil and heavy metal adsorbents with higher adsorption capacity and better regenerative properties.

Exploring microbiome and plankton responses and interactions in the mangrove ecosystem through eDNA and network analysis.

The comprehensive analysis of multiple biological communities is essential for assessing diversities within mangrove ecosystems, yet such studies are infrequent. Environmental DNA (eDNA) facilitates the simultaneous exploration of organisms across various levels within a single ecosystem. In this investigation, 16S rRNA, cytochrome C oxidase I (COI), and Mito-fish primers were employed to characterize the microbiome, eukaryotic plankton, and fish communities, along with their intricate interactions, across 24 samples from three Chinese mangrove reservoirs. The resulting dataset encompasses 3779 taxonomic groups (genus level), spanning from the microbiome to vertebrates. Diversity analysis unveiled a higher level of stability in the microbiome community compared to plankton, underscoring the superior site-specificity of plankton. The association analysis revealed that biodiversity was primarily affected by temperature, turbidity, and fluorescent dissolved organic matter (fDOM). Notably, the physicochemical factors, turbidity, and fDOM had a more pronounced impact on the microbiome than on plankton, explaining their distinct sensitivities to site-specific conditions. Network analysis constructed 15 biological interaction subnetworks representing various community connections. The most connected genera in each subnetwork, highly responsive to different environmental factors, could serve as potential indicators of distinct ecosystem states. In summary, our findings represent the first comparison of the response sensitivities of different communities and the construction of their interaction networks in mangrove environments. These results contribute valuable insights into marine ecosystem dynamics and the role of environmental factors in shaping biodiversity.

Amorphous Cobalt Polyselenides with Hyperbranched Polymer Additive as High-Capacity Magnesium Storage Cathode Materials Through Cationic and Anionic Co-Redox Mechanism.

Rechargeable magnesium batteries (RMBs) are a promising energy-storage technology with low cost and high reliability, while the lack of high-performance cathodes is impeding the development. Herein, a series of amorphous cobalt polyselenides (CoSex, x>2) is synthesized with the assistance of organic amino-terminal hyperbranched polymer (AHP) additive and investigated as cathodes for RMBs. The coordination of cobalt cations with the amino groups of AHP leads to the formation of amorphous CoSex rather than crystalline CoSe2. The amorphous structure is favorable for magnesium-storage reaction kinetics, and the polyselenide anions provide extra capacities besides the redox of cobalt cations. Moreover, the organic AHP molecules retained in CoSex-AHP provide an elastic matrix to accommodate the volume change of conversion reaction. With a moderate x value (2.73) and appropriate AHP content (11.58%), CoSe2.7-AHP achieves a balance between capacity and cycling stability. Amorphous CoSe2.7-AHP provides high capacities of 246.6 and 94 mAh g‒1, respectively, at 50 and 2000 A g‒1, as well as a capacity retention rate of 68.5% after 300 cycles. The mechanism study demonstrates CoSex-AHP undergoes reversible redox of Co2+/3+↔Co0 and Sen 2‒↔Se2‒. The present study demonstrates amorphous polyselenides with cationic-anionic redox activities is as a feasible strategy to construct high-capacity cathode materials for RMBs.

Clinical application of indocyanine green fluorescence navigation technique in laparoscopic common bile duct exploration for complex hepatolithiasis.

BACKGROUND: This study investigated the clinical application of the indocyanine green (ICG) fluorescence navigation technique in bile duct identification during laparoscopic common bile duct exploration (LCBDE) for complex hepatolithiasis. METHODS: Eighty patients with complex hepatolithiasis were admitted to our department between January 2022 and June 2023 and randomly divided into control and observation groups. The control group underwent conventional LCBDE, while the observation group underwent LCBDE guided by ICG fluorescence. RESULTS: Intraoperatively, the observation group had shorter operation and search times for the common bile duct (CBD), as well as reduced intraoperative blood loss and fewer complications, such as conversion to laparotomy and various injuries (gastroduodenal, colon, pancreatic, and vascular) than the control group, with statistical significance (P < 0.05). Postoperatively, the observation group had lower rates of postoperative bile leakage, abdominal infection, postoperative hemorrhage, and residual stone than the control group. Additionally, the observation group demonstrated significantly shorter times for resuming flatus, removal of the abdominal drainage tube, and hospitalization than the control group, with statistical significance (P < 0.05). CONCLUSION: ICG fluorescence navigation technology effectively visualizes the bile duct, improves its identification rate, shortens the operation time, prevents biliary tract injury, and reduces the occurrence of complications.

Impact of pelvic anteversion on spinopelvic alignment in an asymptomatic population: a dynamic perspective of standing and sitting.

BACKGROUND CONTEXT: A subgroup of patients with pelvic anteversion can present with an unusually large degree of lumbar lordosis (LL), a highly sloped sacrum, and a relatively small pelvic incidence (PI). Prior to lumbar surgery, it is can be important to consider such unique sagittal alignment. However, until now, there has been a lack of a predictive model considering different pelvic alignments. Furthermore, the dynamic characteristics of an anteverted pelvis (AP) subgroup have also been unclear. PURPOSE: To build linear predictive formulas for LL that take pelvic anteversion into consideration and to explore the dynamic characteristics of an AP subgroup. STUDY DESIGN: Monocentric, cross-sectional study. PATIENT SAMPLE: 565 asymptomatic Chinese men and women between the ages of 18 and 80 years. OUTCOME MEASURES: Sagittal parameters including LL, lumbar lordosis minus thoracic kyphosis (LL-TK), (PI), pelvic tilt (PT), pelvic incidence minus lumbar lordosis (PI-LL), sacral slope (SS), sacral slope divided by pelvic incidence (SS/PI), sagittal vertical axis (SVA), thoracic kyphosis (TK), and T1 (first thoracic vertebra) pelvic angle (TPA) were measured on whole spine radiographs obtained with participants in standing and sitting positions. METHODS: All participants underwent radiography in the standing position; 235 of them underwent additional radiography in the sitting position to allow measurement of sagittal parameters. The participants with pelvic anteversion were placed in an AP (anteverted pelvis) group. Sagittal parameters were compared between the AP group and the non-AP group, and predictive formulas for LL based on PI were created in both groups. In addition, changes in sagittal parameters from standing to sitting were compared in the AP group and a PI-matched control group. RESULTS: Of the 565 participants, 171 (30.3%) had pelvic anteversion. In comparison with the non-AP group, the AP group presented with larger LL, a larger SS, and a smaller PT, with relatively small PI. The predictive formulas for LL were LL = 0.60°â€¯× PI + 21.60° (R2 = 0.268; P < 0.001) in the whole cohort, LL = 0. 83 × PI + 18.75° (R2 = 0.427; P < 0.001) in AP group, and LL = 0.79°â€¯× PI + 9.66° (R2 = 0.451; P < 0.001) in the non-AP group. In moving from standing to sitting, the AP group presented with a larger decrease in SS and LL compared with the control group, indicating different patterns of spinopelvic motion. CONCLUSIONS: In the cohort examined, 30.3% present with pelvic anteversion. Those with AP present with unique characteristics of spinopelvic alignment. In moving from standing to sitting, they exhibit different patterns of spinopelvic motion. We found that identifying the degree of anteversion in each person improves the accuracy of linear models for predicting the degree of LL, which in turn can make plans for spine surgery more accurate.

Does the Dose of Standard Adjuvant Chemotherapy Affect the Triple-negative Breast Cancer Benefit from Extended Capecitabine Metronomic Therapy? An Exploratory Analysis of the SYSUCC-001 Trial.

Purpose: Results from studies of extended capecitabine after the standard adjuvant chemotherapy in early stage triple-negative breast cancer (TNBC) were inconsistent, and only low-dose capecitabine from the SYSUCC-001 trial improved disease-free survival (DFS). Adjustment of the conventional adjuvant chemotherapy doses affect the prognosis and may affect the efficacy of subsequent treatments. This study investigated whether the survival benefit of the SYSUCC-001 trial was affected by dose adjustment of the standard adjuvant chemotherapy or not. Patients and Methods: We reviewed the adjuvant chemotherapy regimens before the extended capecitabine in the SYSUCC-001 trial. Patients were classified into "consistent" (standard acceptable dose) and "inconsistent" (doses lower than acceptable dose) dose based on the minimum acceptable dose range in the landmark clinical trials. Cox proportional hazards model was used to investigate the impact of dose on the survival outcomes. Results: All 434 patients in SYSUCC-001 trial were enrolled in this study. Most of patients administered the anthracycline-taxane regimen accounted for 88.94%. Among patients in the "inconsistent" dose, 60.8% and 47% received lower doses of anthracycline and taxane separately. In the observation group, the "inconsistent" dose of anthracycline and taxane did not affect DFS compared with the "consistent" dose. Moreover, in the capecitabine group, the "inconsistent" anthracycline dose did not affect DFS compared with the "consistent" dose. However, patients with "consistent" taxane doses benefited significantly from extended capecitabine (P=0.014). The sufficient dose of adjuvant taxane had a positive effect of extended capecitabine (hazard ratio [HR] 2.04; 95% confidence interval [CI] 1.02 to 4.06). Conclusion: This study found the dose reduction of adjuvant taxane might negatively impact the efficacy of capecitabine. Therefore, the reduction of anthracycline dose over paclitaxel should be given priority during conventional adjuvant chemotherapy, if patients need dose reduction and plan for extended capecitabine.

PM2.5 exposure upregulates pro-inflammatory protein expression in human microglial cells via oxidant stress and TLR4/NF-κB pathway.

Exposure to ambient PM2.5 is associated with neurodegenerative disorders, in which microglia activation plays a critical role. Thus far, the underlying mechanisms for PM2.5-induced microglia activation have not been well elucidated. In this study, a human microglial cell line (HMC3) was used as the in vitro model to examine the inflammatory effect (hall marker of microglia activation) of PM2.5 and regulatory pathways. The expression of inflammatory mediators including interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2) as well as the brain derived neurotrophic factor (BDNF) were determined by ELISA and/or real-time PCR, respectively. Flow cytometry was used to measure the production of intracellular reactive oxygen species (ROS). Western blot was used to measure protein levels of Toll-like receptor 4 (TLR4), NF-κB inhibitor α (IκBα) and COX-2. It was shown that PM2.5 stimulation increased IL-6 and COX-2 expression but decreased BDNF expression in a dose-dependent manner. Further studies showed that PM2.5 triggered the formation of ROS and pre-treatment with the ROS scavenger acetylcysteine (NAC) significantly suppressed PM2.5-induced IL-6 and COX-2 expression. Moreover, the nuclear factor kappa B (NF-κB) inhibitor BAY11-7085 or the TLR4 neutralizing antibody markedly blocked PM2.5-induced IL-6 and COX-2 expression. However, NAC or BAY11-7085 exhibited minimal effect on PM2.5-induced BDNF down-regulation. In addition, pre-treatment with BAY11-7085 or TLR4 neutralizing antibody reduced ROS production induced by PM2.5, and NAC pre-treatment inhibited TLR4 expression and NF-κB activation induced by PM2.5. Collectively, PM2.5 treatment induced IL-6 and COX-2 but suppressed BDNF expression. PM2.5-induced IL-6 and COX-2 expression was mediated by interactive oxidative stress and TLR4/NF-κB pathway.

The Effects of Perineural Dexamethasone on Rebound Pain After Nerve Block in Patients with Unicompartmental Knee Arthroplasty A Randomized Controlled Trial.

OBJECTIVES: A single nerve block provides excellent analgesia in a short time, but rebound pain after the nerve block disappears has attracted researchers' attention. The aim of this study is to evaluate the effect of perineural dexamethasone on rebound pain after sciatic nerve block and femoral nerve block in patients undergoing unicompartmental knee arthroplasty (UKA). METHODS: In a double-blinded fashion, We recruited 72 patients undergoing UKA, each of whom received sciatic and femoral nerve block. Patients were randomly assigned to two groups (n=36): X (ropivacaine only) and D (ropivacaine combined with dexamethasone). The primary outcome was the incidence of rebound pain. The secondary outcomes were rebound pain score, the duration of rebound pain, the duration of nerve block, pain score, sufentanil consumption and rescue analgesic, patient-controlled intravenous analgesia, distance walked, sleep quality score, C-reactive protein levels, and adverse effects. RESULTS: Compared with group X, the incidence of rebound pain in group D was higher, the rebound pain score was higher and the duration of nerve block was prolonged (P<0.05). At 12, 16, and 20 hours postoperatively, the pain scores at rest in group D was lower. At 32 and 36 hours postoperatively, the pain scores at rest in group D was higher (P<0.05). Moreover, patients in group D had lower levels of C-reactive protein after surgery (P<0.05). DISCUSSION: Addition of dexmedetomidine to ropivacaine for UKA effectively prolonged the duration of nerve block and decreased c-reactive protein levels, but increased the incidence of rebound pain and rebound pain score, and had no beneficial effects on the postoperative analgesia.

Partial CArdiac Denervation to prevent PostOperative Atrial Fibrillation after coronary artery bypass grafting (pCAD-POAF): study protocol for a randomized controlled trial.

Postoperative atrial fibrillation (POAF) is commonly seen in patients undergoing coronary artery bypass grafting (CABG), increasing the risk of morbidity, mortality and hospital expenses. This study is aimed to evaluate the effect of partial cardiac denervation, which is achieved by cutting off the ligament of Marshall and resecting the fat pad along the Waterston groove, on the prevention of POAF after CABG. Patients planned for CABG at our center will be screened for eligibility for this study. A total of 430 patients will be randomized into intervention (partial cardiac denervation) group and control group. Intraoperative high-frequency electrical stimulation and further histologic analysis will be performed among certain number of patients to confirm the existence of ganglia. All of the patients will be continuously monitored for the incidence of POAF through electrophysiologic device until the 6th day postoperatively, and required to complete a 30-day follow-up (twelve lead electrocardiogram and echocardiogram assesment) after discharge. The primary endpoint is the incidence of POAF, while the secondary endpoints are the cost-effectiveness and safety outcomes. In conclusion, this trial will evaluate whether partial cardiac denervation through cutting off the ligament of Marshall and resecting the fat pad along the Waterston groove can reduce the incidence of POAF after CABG. If this procedure is revealed to be effective and safe, it may provide a potential therapeutic approach to prevent POAF in this group of patients.

Lactoferrin mediates epithelial-mesenchymal transformation by regulating the PI3K/AKT/mTOR pathway to inhibit nasopharyngeal carcinoma metastasis.

Nasopharyngeal carcinoma (NPC) is a common malignant tumor of the head and neck. Epithelial-mesenchymal transition (EMT) is a major player in regulating NPC transfer. There is increasing evidence that lactotransferrin (LTF) is an important regulator of EMT conversion. However, the potential role and mechanisms of LTF in regulating NPC cell EMT remain unclear. In this study, quantitative real-time PCR (qRT‒PCR) and Western blotting were applied to measure the expression of LTF in NPC cells. Subsequently, the influences of LTF on the proliferation, migration and invasion of NPC cells were verified by functional acquisition experiments. Finally, Western blotting was used to analyze the effects of EMT-related proteins and phosphoinositol 3-kinase (PI3K)/Akt/mammalian rapamycin target (mTOR) signaling pathways. The data of this study indicate that LTF was underexpressed in human NPC cells, and upregulation of LTF could restrain NPC cell proliferation, invasion, migration and EMT transformation. Moreover, the effects of LTF on NPC cell metastasis and EMT are partly determined by the PI3K/AKT/mTOR pathway. This study suggests that LTF is a potential biomarker of NPC and that LTF-mediated EMT progression plays a tumor-suppressive role in the progression of NPC metastasis.

Exploring the flavor changes in mung bean flour through lactobacillus fermentation: insights from volatile compounds and non-targeted metabolomics analysis.

BACKGROUND: Mung beans are abundant in nutrition, but their leguminous flavor limits their development. Lactic Acid Bacteria (LAB) fermentation can decrease unwanted bean flavors in legumes and enhance their flavor. This study examined the influence of Lactobacillus fermentation on the flavor characteristics of mung bean flour (MBF) using volatile compounds and non-targeted metabolomics. RESULTS: Lactobacillus plantarum LP90, Lactobacillus casei LC89, and Lactobacillus acidophilus LA85 eliminated 61.37%, 48.29%, and 43.73% of the primary bean odor aldehydes from MBF. The results of relative odor activity values (ROAV) showed that fermented mung bean flour (FMBF) included volatile chemicals that contributed to fruity, flowery, and milky aromas. These compounds included ethyl acetate, hexyl formate, 3-hydroxy-2-butanone, and 2,3-butanedione. The levels of amino acids with a fresh sweet flavor increased significantly by 93.89%, 49.40%, and 35.27% in LP90, LC89, and LA85, respectively. A total of 49 up-regulated and 13 down-regulated significantly differential metabolites were annotated, and 10 metabolic pathways were screened for contributing to the flavor. The correlation between important volatile compounds and non-volatile substances relies on two primary metabolic pathways: the citric acid cycle pathway and the amino acid metabolic system. CONCLUSION: The flavor of MBF was greatly enhanced by the process of Lactobacillus fermentation, with LP90 having the most notable impact. These results serve as a reference for identifying the flavor of FMBF. This article is protected by copyright. All rights reserved.