Upconversion-Mediated Optogenetics for the Treatment of Surgery-Induced Postoperative Neurocognitive Dysfunction.

Perioperative neurocognitive disorder (PND) is a common complication in surgical patients. While many interventions to prevent PND have been studied, the availability of treatment methods is limited. Thus, it is crucial to delve into the mechanisms of PND, pinpoint therapeutic targets, and develop effective treatment approaches. In this study, reduced dorsal tenia tecta (DTT) neuronal activity was found to be associated with tibial fracture surgery-induced PND, indicating that a neuronal excitation-inhibition (E-I) imbalance could contribute to PND. Optogenetics in the DTT brain region was conducted using upconversion nanoparticles (UCNPs) with the ability to convert 808 nm near-infrared light to visible wavelengths, which triggered the activation of excitatory neurons with minimal damage in the DTT brain region, thus improving cognitive impairment symptoms in the PND model. Moreover, this noninvasive intervention to modulate E-I imbalance showed a positive influence on mouse behavior in the Morris water maze test, which demonstrates that UCNP-mediated optogenetics is a promising tool for the treatment of neurological imbalance disorders.

Single-cell analysis reveals the stromal dynamics and tumor-specific characteristics in the microenvironment of ovarian cancer.

High-grade serous ovarian carcinoma (HGSOC) is a heterogeneous disease, and a highstromal/desmoplastic tumor microenvironment (TME) is associated with a poor outcome. Stromal cell subtypes, including fibroblasts, myofibroblasts, and cancer-associated mesenchymal stem cells, establish a complex network of paracrine signaling pathways with tumor-infiltrating immune cells that drive effector cell tumor immune exclusion and inhibit the antitumor immune response. In this work, we integrate single-cell transcriptomics of the HGSOC TME from public and in-house datasets (n = 20) and stratify tumors based upon high vs. low stromal cell content. Although our cohort size is small, our analyses suggest a distinct transcriptomic landscape for immune and non-immune cells in high-stromal vs. low-stromal tumors. High-stromal tumors have a lower fraction of certain T cells, natural killer (NK) cells, and macrophages, and increased expression of CXCL12 in epithelial cancer cells and cancer-associated mesenchymal stem cells (CA-MSCs). Analysis of cell-cell communication indicate that epithelial cancer cells and CA-MSCs secrete CXCL12 that interacte with the CXCR4 receptor, which is overexpressed on NK and CD8+ T cells. Dual IHC staining show that tumor infiltrating CD8 T cells localize in proximity of CXCL12+ tumor area. Moreover, CXCL12 and/or CXCR4 antibodies confirm the immunosuppressive role of CXCL12-CXCR4 in high-stromal tumors.

Single-cell analysis reveals the stromal dynamics and tumor-specific characteristics in the microenvironment of ovarian cancer.

High-grade serous ovarian carcinoma (HGSOC) is a heterogeneous disease, and a high stromal/desmoplastic tumor microenvironment (TME) is associated with a poor outcome. Stromal cell subtypes, including fibroblasts, myofibroblasts, and cancer-associated mesenchymal stem cells, establish a complex network of paracrine signaling pathways with tumor-infiltrating immune cells that drive effector cell tumor immune exclusion and inhibit the antitumor immune response. Single-cell transcriptomics of the HGSOC TME from public and in-house datasets revealed a distinct transcriptomic landscape for immune and non-immune cells in high-stromal vs. low-stromal tumors. High-stromal tumors had a lower fraction of certain T cells, natural killer (NK) cells, and macrophages and increased expression of CXCL12 in epithelial cancer cells and cancer-associated mesenchymal stem cells (CA-MSCs). Analysis of cell-cell communication indicated that epithelial cancer cells and CA-MSCs secreted CXCL12 that interacted with the CXCR4 receptor, which was overexpressed on NK and CD8 + T cells. CXCL12 and/or CXCR4 antibodies confirmed the immunosuppressive role of CXCL12-CXCR4 in high-stromal tumors.

Resveratrol improves ovarian state by inhibiting apoptosis of granulosa cells.

AIM: Among the natural polyphenolic compounds, resveratrol (RES) is known for reducing the effects of declining reproductive power through resisting senility, anti-oxidant and anti-inflammatory, while the molecular mechanism of RES in human ovaries is unclear. We aimed to evaluate the most likely mechanisms of RES against apoptosis induced by H2O2 in human ovary granulosa cells. METHODS: Ovarian granulosa cells from infertile women (≤35 years old) were collected. Those patients defined as polycystic ovary syndrome (PCOS), poor ovarian responder (POR) and Endometriosis were excluded. Then they were randomly divided into control group, model group and the treatment group. Cellular apoptosis was analyzed by flow cytometer method. The related protein and mRNA expressions were detected by western blot and RT-PCR. RESULTS: Apoptosis rates of the treatment group containing RES with concentrations of 1 µM and 10 µM were significantly decreased (p < 0.001). Western blot results demonstrated that the proteins levels of transforming growth factor-ß (TGF-ß), Bax and Caspase 9 were decreased, and Bcl-2 was increased under RES treatment, while the protein levels of Caspase 8, Caspase 3, growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) expressed no significant difference. The results by RT-PCR of follicle and ovarian development related mRNA factors were consistent with that of western blot assay. CONCLUSION: In conclusion, the present study provides the evidence that RES may affects apoptotic factors to protect human ovarian state.

Nomogram for Prediction of Postoperative Delirium after Deep Brain Stimulation of Subthalamic Nucleus in Parkinson's Disease under General Anesthesia.

Introduction: Postoperative delirium can increase cognitive impairment and mortality in patients with Parkinson's disease. The purpose of this study was to develop and internally validate a clinical prediction model of delirium after deep brain stimulation of the subthalamic nucleus in Parkinson's disease under general anesthesia. Methods: We conducted a retrospective observational cohort study on the data of 240 patients with Parkinson's disease who underwent deep brain stimulation of the subthalamic nucleus under general anesthesia. Demographic characteristics, clinical evaluation, imaging data, laboratory data, and surgical anesthesia information were collected. Multivariate logistic regression was used to develop the prediction model for postoperative delirium. Results: A total of 159 patients were included in the cohort, of which 38 (23.90%) had postoperative delirium. Smoking (OR 4.51, 95% CI 1.56-13.02, p < 0.01) was the most important risk factor; other independent predictors were orthostatic hypotension (OR 3.42, 95% CI 0.90-13.06, p=0.07), inhibitors of type-B monoamine oxidase (OR 3.07, 95% CI 1.17-8.04, p=0.02), preoperative MRI with silent brain ischemia or infarction (OR 2.36, 95% CI 0.90-6.14, p=0.08), Hamilton anxiety scale score (OR 2.12, 95% CI 1.28-3.50, p < 0.01), and apolipoprotein E level in plasma (OR 1.48, 95% CI 0.95-2.29, p=0.08). The area under the receiver operating characteristic curve (AUC) was 0.76 (95% CI 0.66-0.86). A nomogram was established and showed good calibration and clinical predictive capacity. After bootstrap for internal verification, the AUC was 0.74 (95% CI 0.66-0.83). Conclusion: This study provides evidence for the independent inducing factors of delirium after deep brain stimulation of the subthalamic nucleus in Parkinson's disease under general anesthesia. By predicting the development of delirium, our model may identify high-risk groups that can benefit from early or preventive intervention.

Pre-operative breathing training based on video learning reduces emergence delirium in preschool children: A randomized clinical trial.

STUDY OBJECTIVE: Emergence delirium is a common complication in preschool children after general anesthesia and may result in undesirable complications. This study aimed to determine whether breathing training after watching an informative video during the pre-operative visit could reduce the incidence of emergence delirium in preschool children after otorhinolaryngologic surgery under general anesthesia. DESIGN: A single-center, double-blinded, randomized controlled trial. SETTING: Perioperative care. PATIENTS: A total of 170 children undergoing otorhinolaryngologic surgery, aged 3-7 years, ASA physical status I or II were involved. INTERVENTIONS: Patients were randomized to receive breathing training during the pre-operative visit (Training group) or to receive pre-operative visit only (Control group) the day before surgery. MEASUREMENTS: Emergence delirium was measured by the Pediatric Anesthesia Emergence Delirium score during the anesthesia recovery time. Data regarding extubation time and post-anesthesia care unit stay time were collected. MAIN RESULTS: Children who received breathing training during the pre-operative visit had a significantly lower incidence of emergence delirium than those who only underwent the pre-operative visit (10.4% vs. 35.1%, P < 0.001). The awakening time score and the maximum score in the post-anesthesia care unit were significantly lower in the training group compared with the control group [4.4 ± 3.4 vs. 6.9 ± 4.2, P < 0.001 and 5.0 (5.0) vs 7.0 (7.0), P = 0.001, respectively]. We found no differences in the extubation time and post-anesthesia care unit stay time between groups. CONCLUSIONS: We concluded that breathing training based on video learning during the pre-operative visit in preschool children undergoing otorhinolaryngologic surgery could significantly decrease the incidence of emergence delirium. TRIAL REGISTRATION: Chinese Clinical Trial Registry (Reference number: ChiCTR1900026162); registered on September 24, 2019.

[Efficacy and Safety of Different Dosages of Decitabine in the Treatment of High-Risk Patients with Myelodysplastic Syndrome].

OBJECTIVE: To investigate the efficacy of high-risk myelodysplastic syndrome (MDS) patients treated by different doses of decitabine (DAC) and its safety. METHODS: Thirty patients with high-risk MDS were all treated by demethylation drug DAC. According to the doses of DAC, 30 patients were divided into 10-day regimen [6 mg/(m2·d)×10 d, 15 patients] group and 5-day regimen [15 mg/(m2·d)×5 d, 15 patients] group. The efficacy and adverse events of the patients in the two groups were observed. RESULTS: The patients were followed up to May 2020, in the 10-day regimen group, 10 cases achieved complete remission (CR), 3 cases achieved partial remission (PR), and 2 cases were progressive disease (PD). Four cases died, including 1 case for heart failure, 2 cases for respiratory failure and 1 case for serious infection. In the 5-day regimen group, 11 cases achieved CR, 1 case achieved PR, 3 cases were PD. Five cases died, including 2 cases for heart failure and 3 for serious infection. The CR rate and ORR of the patients in the two groups were 66.67% vs 73.33%, 86.67% vs 80.00%, respectively, which showed no significant differences, and the efficacy also showed no significant difference. After treatment, the levels of WBC, NE, Hb and PLT of the patients in 10-day regimen group were higher than those in 5-day regimen. In the 10-day regimen group, there were 11 cases of pneumonia, 2 cases of bacteremia, 1 case of skin infection and 1 case of urinary tract infection. While in the 5-day regimen group, 13 cases of pneumonia, 5 cases bacteremia, 1 case of skin infection and 3 cases of urinary tract infection. There were 2 cases with mild gastrointestinal response in the 10-day regimen group, and 7 cases with obvious nausea and anorexia in the 5-day regimen group. The symptoms were relieved after the treatment of acid suppression, stomach protection and antiemetic. The liver, kidney and heart function were monitored. One case liver function damage and 2 cases cardiac insufficiency were observed in the 10-day regimen group. Seven cases regimen cardiac insufficiency and 4 cases regimen liver function damage were observed in the 5-day regimen group. CONCLUSION: 10-day regimen and 5-day regimen are equally effective, but 10-day regimen is less myelosuppressive and more safer, which can be applied in clinical.

Cancer-associated MSC drive tumor immune exclusion and resistance to immunotherapy, which can be overcome by Hedgehog inhibition.

We investigated the impact of cancer-associated mesenchymal stem cells (CA-MSCs) on ovarian tumor immunity. In patient samples, CA-MSC presence inversely correlates with the presence of intratumoral CD8+ T cells. Using an immune "hot" mouse ovarian cancer model, we found that CA-MSCs drive CD8+ T cell tumor immune exclusion and reduce response to anti­PD-L1 immune checkpoint inhibitor (ICI) via secretion of numerous chemokines (Ccl2, Cx3cl1, and Tgf-ß1), which recruit immune-suppressive CD14+Ly6C+Cx3cr1+ monocytic cells and polarize macrophages to an immune suppressive Ccr2hiF4/80+Cx3cr1+CD206+ phenotype. Both monocytes and macrophages express high levels of transforming growth factor ß­induced (Tgfbi) protein, which suppresses NK cell activity. Hedgehog inhibitor (HHi) therapy reversed CA-MSC effects, reducing myeloid cell presence and expression of Tgfbi, increasing intratumoral NK cell numbers, and restoring response to ICI therapy. Thus, CA-MSCs regulate antitumor immunity, and CA-MSC hedgehog signaling is an important target for cancer immunotherapy.

Optimized Propofol Anesthesia Increases Power of Subthalamic Neuronal Activity in Patients with Parkinson's Disease Undergoing Deep Brain Stimulation.

INTRODUCTION: Propofol is a general anesthetic option for deep brain stimulation (DBS) of the subthalamic nucleus (STN) of patients with Parkinson's disease (PD). However, its effects on STN activity and neuropsychological outcomes are controversial. The optimal propofol anesthesia for asleep DBS is unknown. This study investigated the safety and effectiveness of an optimized propofol anesthesia regimen in asleep DBS. METHODS: This retrospective study enrolled 68 PD patients undergoing bilateral STN-DBS surgery. All patients received local scalp anesthesia, with (asleep group, n = 35) or without (awake group, n = 33) propofol-remifentanil general anesthesia by target-controlled infusion under electroencephalogram monitoring. The primary outcome was subthalamic neuronal spiking characterization during microelectrode recording. The secondary outcomes were clinical outcomes including motor, cognition, mind, sleep, and quality of life at 6 months. RESULTS: Significantly increased delta and theta power were obtained under propofol anesthesia (awake vs. asleep group, mean ± standard deviation; delta: 31.97 ± 9.87 vs. 39.77 ± 10.56, p < 0.01; theta: 21.09 ± 5.55 vs. 24.82 ± 6.63, p = 0.01). After excluding the influence of confounding factors of age and preoperative motor scores, there was a statistically significant influence on the delta, theta, and alpha power of STN neuronal activity under different anesthesia regimens (delta: ß = 2.64, p < 0.01; theta: ß = 2.11, p < 0.01; alpha: ß = 1.42, p = 0.01). There were no differences in modified burst index, firing rate, tract numbers of microelectrode recording, and other clinical outcomes between the two groups. CONCLUSION: Optimized propofol anesthesia enhanced the delta, theta, and alpha power in STN compared with the awake technique and likely contributed to target recognition under propofol anesthesia. These results demonstrate that propofol is suitable, but needs to be optimized, for asleep STN-DBS. TRIAL REGISTRATION: Chinese Clinical Trial Registry Identification number: ChiCTR2100045942. Registered 29 April 2021-Retrospectively registered.

Na+ , K+ -ATPase participates in the protective mechanism of rat cerebral ischemia-reperfusion through the interaction with glutamate transporter-1.

Glutamate excitotoxicity in cerebral ischemia/reperfusion is an important cause of neurological damage. The aim of this study was to investigate the mechanism of Na+, K+-ATPase (NKA) involved in l ow concentration of ouabain (Oua, activating NKA)-induced protection of rat cerebral ischemia-reperfusion injury. The 2,3,5-triphenyltetrazolium chloride (TTC) staining and neurological deficit scores (NDS) were performed to evaluate rat cerebral injury degree respectively at 2 h, 6 h, 1 d and 3 d after reperfusion of middle cerebral artery occlusion (MCAO) 2 h in rats. NKA α1/α2 subunits and glutamate transporter-1 (GLT-1) protein expression were investigated by Western blotting. The cerebral infarct volume ratio were evidently decreased in Oua group vs MCAO/R group at 1 d and 3 d after reperfusion of 2 h MCAO in rats (*p ＜ 0.05 ). Moreover, NDS were not significantly different (p ＞ 0.05 ). NKA α1 was decreased at 6 h and 1 d after reperfusion of 2 h MCAO in rats, and was improved in Oua group. However, NKA α1 and α2 were increased at 3 d after reperfusion of 2 h MCAO in rats, and was decreased in Oua group. GLT-1 was decreased at 6 h, 1 d and 3 d after reperfusion of 2 h MCAO in rats, and was improved in Oua group. These data indicated that l ow concentration of Oua could improve MCAO/R injury through probably changing NKA α1/α2 and GLT-1 protein expression, then increasing GLT-1 function and promoting Glu transport and absorption, which could be useful to determine potential therapeutic strategies for patients with stroke. Low concentration of Oua improved rat MCAO/R injury via NKA α1/α2 and GLT-1.

Efficacy and safety of triamcinolone acetonide injection combined with laser photocoagulation in the treatment of diabetic macular edema: a systematic review and meta-analysis.

BACKGROUND: Diabetic macular edema (DME) is a type of retinopathy caused by diabetes, and the 2 main clinical treatment modalities are drug therapy intravitreal triamcinolone acetonide injection (IVTA) and laser photocoagulation. This meta-analysis investigated the efficacy of combining both the 2 treatment modalities. METHODS: The Embase, Cochrane library, PubMed, and Ovid databases were searched for English literatures. The literatures were screened and assessed for the risk of bias, after that the Revman 5.4 software was used to conduct the meta-analysis. RESULTS: A total of 8 articles, including 549 patients, were included in this study. Meta-analysis showed that the effect of (IVTA + laser) on early central macular thickness (CMT) was not significantly different with IVTA alone [mean difference (MD) =-5.13, 95% confidence interval (CI): -17.06 to 6.80, P=0.40], however, significantly different with laser alone (MD =-94.31, 95% CI: -135.04 to -53.58, P<0.00001). Similarly, the effect of (IVTA + laser) on early best corrected visual acuity (BCVA) was not significantly different with IVTA alone (MD =0.02, 95% CI: -0.03 to 0.07, Z=0.79, P=0.43). but different with laser alone [MD =-0.20, 95% CI: -0.24 to -0.16, Z=10.16, P<0.00001). The effect of (IVTA + laser) on long-term CMT was not significantly different with IVTA alone (MD =-66.90, 95% CI: -132.66 to -1.15, Z=1.99, P=0.05) nor with laser alone (MD =-15.86, 95% CI: -31.37 to -0.35, Z=2.00, P=0.05). Similarly, the effect of combined intervention (IVTA + laser) on long-term BCVA was not significantly different with IVTA alone (MD =-0.18, 95% CI: -0.39 to 0.03, Z=1.71, P=0.09) nor with laser alone (MD =-0.11, 95% CI: -0.23 to 0.01, Z=1.74, P=0.08). Administration of IVTA before laser was superior to laser alone (MD =-0.19, 95% CI: -0.31 to -0.07, Z=3.09, P=0.002). DISCUSSION: The effect of IVTA + laser therapy is similar to IVTA alone, but superior to laser alone for the early treatment of DME. However, the long-term effect is similar to IVTA alone or laser alone, a better therapeutic effect can be achieved if IVTA is administered before laser treatment.

Recent advances in nanomaterial-based biosensors for the detection of exosomes.

Exosomes are a type of extracellular vesicle actively secreted by almost all eukaryotic cells. They are ideal candidates for reliable next-generation biomarkers in the early diagnosis and therapeutic response evaluation of cancer. Thus, the quantification of exosomes is crucial in facilitating clinical research and application. Compared with traditional materials, nanomaterials have better optical, magnetic, electrical, and catalytic properties due to their small size, high specific surface area, and variable structure. The incorporation of nanomaterials into sensing systems is an attractive approach towards improving sensitivity and can provide improved sensor selectivity and stability. In this paper, we summarize the progress in nanomaterial-based exosome detection methods, including electrochemical biosensors, photoelectrochemical biosensors, colorimetric biosensors, fluorescence biosensors, chemiluminescence biosensors, electrochemiluminescence biosensors, surface plasmon resonance biosensors, and surface-enhanced Raman spectroscopy biosensors. Moreover, future research directions and challenges in exosome detection methods are discussed. We hope that this article will offer an overview of nanomaterial-based exosome detection techniques and open new avenues in disease research.Graphical abstract.

Effects of Fungal Polysaccharide on Oxidative Damage and TLR4 Pathway to the Central Immune Organs in Cadmium Intoxication in Chickens.

Cadmium (Cd) can cause animal organism damage, but there have been few studies on the damage of cadmium to the immune organs of birds. Most fungal polysaccharide has antioxidant and immunomodulatory effects. The experimental study investigated the effects of fungal polysaccharide (Agaricus blazei Murill polysaccharide and Ganoderma luciduccharide) on the oxidative damage of central immune organs (thymus and bursa of Fabricius) and on the Toll-like receptor 4 (TLR4) pathway in cadmium-poisoned chickens. The results showed that Agaricus blazei polysaccharide and Ganoderma lucidum polysaccharide can reduce cadmium content, TLR4 expression, inflammatory factor (IL-1ß, IL-6, TNF-α) content, and lipid peroxidation product MDA content and increase the activity of antioxidant enzymes SOD and GSH-Px in thymus and bursa of cadmium poisoning chickens. Ganoderma lucidum polysaccharide could decrease the expression of TLR4, IL-1ß, and IL-6 in cadmium poisoning peripheral blood lymphocytes of chicken, and TLR4 inhibitor had the same effect. The results demonstrated the protective effects of Agaricus blazei Murill polysaccharide and Ganoderma lucidum polysaccharides on the damage of the central immune organs of chickens caused by cadmium poisoning were closely related to the TLR4 signaling pathway and oxidative stress.

A Novel Fabricating Process of Catalytic Gas Sensor Based on Droplet Generating Technology.

Catalytic gas sensors are widely used for measuring concentrations of combustible gases to prevent explosive accidents in industrial and domestic environments. The typical structure of the sensitive element of the sensor consists of carrier and catalyst materials, which are in and around a platinum coil. However, the size of the platinum coil is micron-grade and typically has a cylindrical shape. It is extremely difficult to control the amount of carrier and catalyst materials and to fulfill the inner cavity of the coil, which adds to the irreproducibility and uncertainty of the sensor performance. To solve this problem, this paper presents a new method which uses a drop-on-demand droplet generator to add the carrier and catalytic materials into the platinum coil and fabricate the micropellistor. The materials in this article include finely dispersed Al2O3 suspension and platinum palladium (Pd-Pt) catalyst. The size of the micropellistor with carrier material can be controlled by the number of the suspension droplets, while the amount of Pd-Pt catalyst can be controlled by the number of catalyst droplets. A bridge circuit is used to obtain the output signal of the gas sensors. The original signals of the micropellistor at 140 mV and 80 mV remain after aging treatment. The sensitivity and power consumption of the pellistor are 32 mV/% CH4 and 120 mW, respectively.

Rhizopus nigricans polysaccharide activated macrophages and suppressed tumor growth in CT26 tumor-bearing mice.

In this study, a homogeneous polysaccharide (RPS-1) was extracted from liquid-cultured mycelia of Rhizopus nigricans. The weight-average molecular weight of RPS-1 was 1.617 × 107 g/mol and structural characterization indicated that RPS-1 was a non-starch glucan which consisted of a backbone structure of (1→4)-linked α-d-glucopyranosyl residues substituted at the O-6 position with α-d-glucopyranosyl branches. RPS-1 stimulated the production of nitric oxide and tumor necrosis factor-α by triggering phosphorylation of mitogen-activated protein kinases and nuclear translocation of nuclear factor kappa B p65 in RAW 264.7 macrophage cells. Moreover, intragastric administration of RPS-1 improved the immune function of CT26 tumor-bearing mice and significantly inhibited the growth of transplanted tumor. In combination with 5-FU, RPS-1 enhanced antitumor activity of 5-FU and alleviated its toxicity on immune system. These findings suggested that RPS-1 has the potential for the development of functional foods and dietary supplements.

Continuous micro-feeding of fine cohesive powders actuated by pulse inertia force and acoustic radiation force in ultrasonic standing wave field.

Stable continuous micro-feeding of fine cohesive powders has recently gained importance in many fields. However, it remains a great challenge in practice because of the powder aggregate caused by interparticle cohesive forces in small capillaries. This paper describes a novel method of feeding fine cohesive powder actuated by a pulse inertia force and acoustic radiation force simultaneously in an ultrasonic standing wave field using a tapered glass nozzle. Nozzles with different outlet diameters are fabricated using glass via a heating process. A pulse inertia force is excited to drive powder movement to the outlet section of the nozzle in a consolidated columnar rod mode. An acoustic radiation force is generated to suspend the particles and make the rod break into large quantities of small agglomerates which impact each other randomly. So the aggregation phenomenon in the fluidization of cohesive powders can be eliminated. The suspended powder is discharged continuously from the nozzle orifice owing to the self-gravities and collisions between the inner particles. The micro-feeding rates can be controlled accurately and the minimum values for RespitoseSV003 and Granulac230 are 0.4 mg/s and 0.5 mg/s respectively. The relative standard deviations of all data points are below 0.12, which is considerably smaller than those of existing vibration feeders with small capillaries.

Horseradish peroxidase-mediated synthesis of an antioxidant gallic acid-g-chitosan derivative and its preservation application in cherry tomatoes.

Owing to their good solubility and film-forming properties, phenolic acid-g-chitosan derivatives can be used for preservation of fruits and vegetables. However, the chemical synthesis used for the preparation of these derivatives poses a great challenge to food safety. In this study, a method involving horseradish peroxidase catalysis was used to prepare a gallic acid-g-chitosan derivative. The grafting mechanism was studied. Then, the derivative's ability to scavenge free radicals and its preserving application in cherry tomatoes were evaluated. The results indicated that the reaction for horseradish peroxidase catalysis occurred between the amino group of chitosan and the carboxyl group of gallic acid. After enzymatic grafting, the gallic acid-g-chitosan derivative possessed excellent antioxidant abilities in scavenging DPPH, hydroxyl, and superoxide anion radicals. When the derivative was used for the preservation of cherry tomatoes, the results showed that it could effectively protect the ascorbate-glutathione cycle and antioxidant enzyme system of cherry tomatoes and inhibit enzymatic browning. In addition, since this derivative delayed the postharvest senescence of cherry tomatoes, the aroma compounds remain relatively constant throughout the storage period.

The regulation of FOXO1 and its role in disease progression.

Cell proliferation, apoptosis, autophagy, oxidative stress and metabolic dysregulation are the basis of many diseases. Forkhead box transcription factor O1 (FOXO1) changes in response to cellular stimulation and maintains tissue homeostasis during the above-mentioned physiological and pathological processes. Substantial evidences indicate that FOXO1's function depends on the modulation of downstream targets such as apoptosis- and autophagy-associated genes, anti-oxidative stress enzymes, cell cycle arrest genes, and metabolic and immune regulators. In addition, oxidative stress, high glucose and other stimulations induce the regulation of FOXO1 activity via PI3k-Akt, JNK, CBP, Sirtuins, ubiquitin E3 ligases, etc., which mediate multiple signalling pathways. Subsequent post-transcriptional modifications, including phosphorylation, ubiquitination, acetylation, deacetylation, arginine methylation and O-GlcNAcylation, activate or inhibit FOXO1. The regulation of FOXO1 and its role might provide a significant avenue for the prevention and treatment of diseases. However, the subtle mechanisms of the post-transcriptional modifications and the effect of FOXO1 remain elusive and even conflicting in the development of many diseases. The determination of these questions potentially has implications for further research regarding FOXO1 signalling and the identification of targeted drugs.

Combined liver-kidney perfusion enhances protective effects of normothermic perfusion on liver grafts from donation after cardiac death.

It has been shown that combined liver-kidney normothermic machine perfusion (NMP) is able to better maintain the circuit's biochemical milieu. Nevertheless, whether the combined perfusion is superior to liver perfusion alone in protecting livers from donation after circulatory death (DCD) is unclear. We aimed to test the hypothesis and explored the mechanisms. Livers from 15 DCD pig donors were subjected to either static cold storage (group A), liver-alone NMP (group B), or combined liver-kidney NMP (group C). Livers were preserved for 6 hours and reperfused ex vivo for 2 hours to simulate transplantation or were transplanted in situ. During perfusion, group C showed an improved acid-base and biochemical environment in the circuit over group B. After reperfusion, the architecture of the liver grafts was best preserved in group C, followed by group B, then group A, as shown by the histology and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling staining of both hepatocytes and biliary epithelium. Ki-67 staining showed substantial hepatocyte proliferation and biliary epithelial regeneration after perfusion in group B and group C. Group C produced more bile in the reperfusion phase than those in group A and group B, with more physiological bile composition and less severe biliary epithelium injury. Von Willebrand factor-positive endothelial cells and E-selectin expression decreased in both group B and group C. Combined liver-kidney NMP not only produced more adenosine triphosphate, protected the nitric oxide signaling pathway, but also diminished oxidative stress (high mobility group box-1 protein and 8-hydroxy-2-deoxy guanosine levels) and inflammatory cytokine (IL6 and IL8) release when compared with liver-alone NMP and CS. In addition, the 7-day survival rate of liver transplant recipients was higher in group C than that in groups A and B. In conclusion, combined liver-kidney NMP can better protect DCD livers from warm ischemia and reperfusion injury probably by maintaining the stability of the internal environment and by abolishing oxidative stress injury. Liver Transplantation 24 67-79 2018 AASLD.

Astragalus Polysaccharide Protect against Cadmium-Induced Cytotoxicity through the MDA5/NF-κB Pathway in Chicken Peripheral Blood Lymphocytes.

Cadmium (Cd) is a known environmental pollutant that is associated with inflammation, oxidative stress, and cell apoptosis. Astragalus polysaccharide (APS) is a major component of Astragalus membranaceus, a vital qi-reinforcing herb medicine with favorable immuneregulation properties. To study the effect of APS on the inhibition of the cadmium-induced injury of peripheral blood lymphocytes (PBLs) in chickens through the MDA5/NF-κB signaling pathway, PLBs acquired from 15-day-old chickens were divided into control group, Cd group, APS + Cd group, anti-MDA5 mAb + Cd group, BAY 11-7082 (a nuclear factor kappa-light chain-enhancer of activated B cells [NF-κB] inhibitor) +Cd group, APS group, anti-MDA5 mAb group, and BAY 11-7082 group. The transcription levels of melanoma differentiation-associated gene 5 (MDA5), interferon promoter-stimulating factor 1 (IPS-1), NF-κB, and inflammatory factors tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 were measured by quantitative real-time PCR. MDA5 protein expression was measured by western blotting. Levels of malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) were measured by corresponding antioxidant kit. The morphological change of PBLs was measured by transmission electron microscopy. The results showed that Cd significantly increased the expression of MDA5, IPS-1, NF-κB, and their downstream cytokines, IL-1ß and TNF-α, IL-6 in PLBs. In addition, a high level of MDA was observed in the Cd treatment group; the activities of GSH-Px and SOD were significantly lower in the Cd treatment group than those in controls (p < 0.05). Ultrastructural changes of PBLs showed that Cd promoted autophagy, apoptosis, and necrosis in PBLs. However, APS can efficiently improve Cd-induced cell damage by decreasing the activation of the MDA5 signaling pathway. The effect is consistent with that of anti-MDA5 mAb or/and BAY. The results indicated that APS inhibited Cd-induced cytotoxicity through the regulation of MDA5/NF-κB signaling.