Cyclo[2]pyridine[8]pyrrole: An Expanded Porphyrinoid with Three Closed-Shell Oxidation States.

We report here an expanded porphyrinoid, cyclo[2]pyridine[8]pyrrole, 1, that can exist at three closed-shell oxidation levels. Macrocycle 1 was synthesized via the oxidative coupling of two open chain precursors and fully characterized by means of NMR and UV-vis spectroscopies, MS, and X-ray crystallography. Reduction of the fully oxidized form (1, blue) with NaBH4 produced either the half-oxidized (2, teal) or fully reduced forms (3, pale yellow), depending on the amount of reducing agent used and the presence or absence of air. Reduced products 2 or 3 can be oxidized to 1 by various oxidants (quinones, FeCl3, and AgPF6). Macrocycle 1 also undergoes proton-coupled reductions with I-, Br-, Cl-, SO32-, or S2O32- in the presence of an acid. Certain thiol-containing compounds likewise reduce 1 to 2 or 3. This conversion is accompanied by a readily discernible color change, making cyclo[2]pyridine[8]pyrrole 1 able to differentiate biothiols, such as cysteine (Cys), homocysteine (Hcy), and glutathione (GSH).

Fetal overgrowth and weight trajectories during infancy and adiposity in early childhood.

BACKGROUND: Large-for-gestational age (LGA), a marker of fetal overgrowth, has been linked to obesity in adulthood. Little is known about how infancy growth trajectories affect adiposity in early childhood in LGA. METHODS: In the Shanghai Birth Cohort, we followed up 259 LGA (birth weight >90th percentile) and 1673 appropriate-for-gestational age (AGA, 10th-90th percentiles) children on body composition (by InBody 770) at age 4 years. Adiposity outcomes include body fat mass (BFM), percent body fat (PBF), body mass index (BMI), overweight/obesity, and high adiposity (PBF >85th percentile). RESULTS: Three weight growth trajectories (low, mid, and high) during infancy (0-2 years) were identified in AGA and LGA subjects separately. BFM, PBF and BMI were progressively higher from low- to mid-to high-growth trajectories in both AGA and LGA children. Compared to the mid-growth trajectory, the high-growth trajectory was associated with greater increases in BFM and the odds of overweight/obesity or high adiposity in LGA than in AGA children (tests for interactions, all P < 0.05). CONCLUSIONS: Weight trajectories during infancy affect adiposity in early childhood regardless of LGA or not. The study is the first to demonstrate that high-growth weight trajectory during infancy has a greater impact on adiposity in early childhood in LGA than in AGA subjects. IMPACT: Large-for-gestational age (LGA), a marker of fetal overgrowth, has been linked to obesity in adulthood, but little is known about how weight trajectories during infancy affect adiposity during early childhood in LGA subjects. The study is the first to demonstrate a greater impact of high-growth weight trajectory during infancy (0-2 years) on adiposity in early childhood (at age 4 years) in subjects with fetal overgrowth (LGA) than in those with normal birth size (appropriate-for-gestational age). Weight trajectory monitoring may be a valuable tool in identifying high-risk LGA children for close follow-ups and interventions to decrease the risk of obesity.

Effect and mechanism of Yiqing decoction on hyperuricemia rats.

This study aimed to experimentally compare the uric acid-lowering effect and renal protection of Yiqing Fang in a rat model of hyperuricemia. Additionally, we used network pharmacology to predict the potential active components, targets, and pathways of Yiqing Fang. Male SD rats were randomly divided into control, model, Yiqing Fang, allopurinol, and probenecid groups. Serum creatinine (Scr), blood urea nitrogen (BUN), serum uric acid (UA), alanine transaminase (ALT), complete blood count, and urinary NAG enzyme levels were measured. Standard pathology and electron microscopy samples were prepared from the left kidney to observe renal pathological changes, renal fibrosis, and collagen III expression levels. In addition, we employed network pharmacology to investigate the molecular mechanisms and pathways of Yiqing Fang. The Yiqing Fang group showed significantly lower levels of Scr, BUN, UA, ALT, urinary NAG enzyme, complete blood count, and liver function tests compared to the model group (P < 0.05). Furthermore, both the Yiqing Fang and allopurinol groups exhibited significant reductions in renal pathological changes compared to the model group, along with decreased expression of collagen III. Network pharmacology analysis identified a total of 27 specific sites related to hyperuricemia. The main active components were predicted to include quercetin, berberine, beta-sitosterol, epimedin C, and dioscin. The primary target sites were predicted to include TNF, IL-6, IL-17, IL-1B, and VEGFA. Yiqing Fang may exert its effects through regulation of drug response, urate metabolism, purine compound absorption, inflammation response, lipopolysaccharide response, cytokine activity, and antioxidant activity. These effects may be mediated through signaling pathways such as IL-17, HIF-1, and AGE-RAGE. Yiqing Fang offers potential as a treatment for hyperuricemia due to its multiple active components, targeting of various sites, and engagement of multiple pathways.

Histone crotonylation regulates neural stem cell fate decisions by activating bivalent promoters.

Histone lysine crotonylation (Kcr), an evolutionarily conserved and widespread non-acetyl short-chain lysine acylation, plays important roles in transcriptional regulation and disease processes. However, the genome-wide distribution, dynamic changes, and associations with gene expression of histone Kcr during developmental processes are largely unknown. In this study, we find that histone Kcr is mainly located in active promoter regions, acts as an epigenetic hallmark of highly expressed genes, and regulates genes participating in metabolism and proliferation. Moreover, elevated histone Kcr activates bivalent promoters to stimulate gene expression in neural stem/progenitor cells (NSPCs) by increasing chromatin openness and recruitment of RNA polymerase II (RNAP2). Functionally, these activated genes contribute to transcriptome remodeling and promote neuronal differentiation. Overall, histone Kcr marks active promoters with high gene expression and modifies the local chromatin environment to allow gene activation.

New Suggested Enhancing Safe Apneic Time in Edentulous Elderly: A Comparison of Transnasal Humidified Rapid-Insufflation Ventilatory Exchange and Facemask.

BACKGROUND Edentulous elderly patients often face challenges in airway management and are susceptible to hypoxemia. Transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) provides high-flow nasal oxygenation, potentially extending safe apneic time (SAT). This study compared the efficacy of THRIVE versus facemask ventilation in improving oxygenation and extending SAT in edentulous elderly patients. MATERIAL AND METHODS Patients with more than 10 missing teeth and who were over 65 years old were randomly assigned to the facemask group (Group M, n=25) or the THRIVE group (Group T, n=25). Patients in Group M were pre-oxygenated with a facemask (6 L/min, FiO2 100%), while patients in Group T were pre-oxygenated with their mouths closed via THRIVE (30 L/min, FiO2 100%). After anesthesia induction, patients in Group M were ventilated with pressure-controlled ventilation. In Group T, the patient's mouth was kept closed, and the flow rate was adjusted to 70 L/min. Four min after cisatracurium administration, ventilation was stopped in Group M while Group T continued to receive oxygen (70 L/min, FiO2 100%).The primary outcome was SAT, which was attained at 4 min after injection of cisatracurium and ended when SpO2 decreased to 95% or when apneic time reached 480 s. A secondary outcome was the reoxygenation time, defined as the time from the beginning of mechanical ventilation to the time when SpO2 98% was reached. RESULTS An SAT of 480 s was reached by all patients in Group T, but by only 6 patients in Group M (P<0.05). Compared with Group M, the reoxygenation time in Group T was significantly shorter (P<0.05). CONCLUSIONS As compared to facemask, THRIVE can extend the SAT, improve oxygenation, and reduce reoxygenation time.

Comparing the Effectiveness and Safety of MedAn with the Nishikawa Blade and UE Videolaryngoscopes for Left-Sided Double-Lumen Endobronchial Tube Intubation: A Randomized Controlled Trial.

BACKGROUND The purpose of this study was to compare the effectiveness and safety of the MedAn videolaryngoscope with the Nishikawa blade (MedAn) vs the UE videolaryngoscope (UE) for intubation with a left-sided double-lumen endobronchial tube (LDLT) in patients with normal airways. MATERIAL AND METHODS We randomly categorized 106 patients scheduled to undergo elective thoracic surgery with LDLT for one-lung ventilation into 2 groups: the UE group (Group UE) and the MedAn group (Group MedAn), using the MedAn or UE for LDLT intubation. The primary outcome was time to successful intubation. The Cormack-Lehane classification of laryngeal view was the key secondary outcome. Other secondary outcomes included first-attempt and overall intubation success rates, laryngoscopy time, LDLT placement time, operators' subjective evaluation of videolaryngoscopes, hemodynamic changes during videolaryngoscopic intubation, and adverse outcomes. RESULTS The time to successful intubation and LDLT placement time of Group MedAn were 42.0 (32.35, 47.0) s and 23.0 (18.0, 26.0) s, and it was shorter than in Group UE (median, 42 s vs 49 s, 23 s vs 30 s, P<0.001). Group MedAn had a better laryngeal view (P=0.03) and less subglottic/tracheal mucosal injury (P<0.001) than Group UE. Moreover, the operators' subjective grading of ease of laryngoscopy, quality of view, and ease of LDLT placement were higher in Group MedAn than in Group UE (P<0.05). CONCLUSIONS Compared with the UE, the MedAn could reduce the intubation time and provide a better laryngeal view and sufficient intubation space for safer LDLT intubation in patients with normal airways.

Paracoccus everestensis sp. nov., a novel bacterium with great antioxidant capacity isolated from the north slope of Mount Everest.

A bacterial strain, designated S8-55T, was isolated from moraine samples collected from the north slope of Mount Everest at an altitude of 5 500 m above sea level. The purpose of this study was to describe a novel species and its characteristics, through genome sequencing and analysis of the relationship between the members of the genus Paracoccus, and explore the antioxidant capacity of strain S8-55T. The polyphasic study confirmed the affiliation of strain S8-55T with the genus Paracoccus. Strain S8-55T was aerobic, Gram-negative and oxidase- and catalase positive. Cells were orange-pigmented, ellipsoid and had no spore formation, no flagella and no motility. Strain S8-55T grow at 10-37 °C, pH 7-11 and without NaCl. Ubiquinone 10 was its predominant respiratory menaquinone. The polar lipids of strain S8-55T were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, an unidentified phospholipid, an unidentified aminolipid and three unidentified lipids. Its major fatty acids were summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c). The G+C content was 64.3 mol%. The phylogenetic analysis based on the 16S rRNA sequence showed that strain S8-55T was closely related to Paracoccus angustae E6T (97.9 %), Paracoccus aerius 011410T (97.9 %) and Paracoccus hibisci THG-T2.8T (97.8 %). The average nucleotide identity values among strain S8-55T and P. angustae CCTCC AB 2015056T, P. aerius KCTC 42845T and P. hibisci CCTCC AB 2016181T were 84.1, 84.5 and 76.3 %, respectively. The genome of strain S8-55T contained antioxidant genes such as oxyR, recD, katE, recD and rpoH. Based on its morphological, physiological and chemical taxonomic characteristics, strain S8-55T (=JCM 35 227T=GDMCC 1.3026T) should be classified as a novel species of the genus Paracoccus with the proposed name Paracoccus everestensis sp. nov.

Comparison of the Effectiveness of Transnasal Humidified Rapid Insufflation Ventilator Exchange (THRIVE) with Facemask Pre-Oxygenation in 40 Patients ≥65 Years of Age Undergoing General Anaesthesia During Gastrointestinal Surgery for Intestinal Obstruction.

BACKGROUND In this study, we aimed to compare the effectiveness of transnasal humidified rapid insufflation ventilator exchange (THRIVE) with facemask pre-oxygenation in 40 patients ≥65 years of age undergoing general anesthesia during gastrointestinal surgery for intestinal obstruction. MATERIAL AND METHODS Patients with gastrointestinal obstruction were randomized to either a facemask group (group M, n=20) or THRIVE group (group T, n=20). During pre-oxygenation, the 2 groups used a facemask (100% oxygen, 6 L/min) and THRIVE (100% oxygen, 40 L/min) to supply oxygen, respectively. Induction of anesthesia was performed in both groups using facemasks and without mechanical or assisted ventilation. The intubation occurred after myorelaxant action began. When the peripheral oxygen saturation (SpO2) dropped below 95%, or 480 s after administration of muscle relaxants, mechanical ventilation was initiated immediately. The primary outcome was arterial partial pressure of oxygen (PaO2) at 5 min after pre-oxygenation. A secondary outcome was time to SpO2 of 95% during apnea, with a cut-off time of 480 s. RESULTS PaO2 at 5 min after pre-oxygenation was (261.5±30.9) mmHg for group M and (446.1±84.4) mmHg for group T (P<0.001). Based on survival analysis, the median time-to-event in group T was 480 s (95% CI 415.7 s - upper limit unknown) and 240 s (95% CI 225.9-254.1 s) in group M (P<0.001). CONCLUSIONS In elderly patients undergoing rapid sequence induction, pre-oxygenation with THRIVE could improve oxygenation and extend safe apnea time, compared with facemask pre-oxygenation.

The effect of varying inhaled oxygen concentrations of high-flow nasal cannula oxygen therapy during gastroscopy with propofol sedation in elderly patients: a randomized controlled study.

BACKGROUND: Despite evidence that high-flow nasal cannula oxygen therapy (HFNC) promotes oxygenation, its application in sedated gastroscopy in elderly patients has received little attention. This study investigated the effect of different inhaled oxygen concentrations (FiO2) of HFNC during sedated gastroscopy in elderly patients. METHODS: In a prospective randomized single-blinded study, 369 outpatients undergoing regular gastroscopy with propofol sedation delivered by an anesthesiologist were randomly divided into three groups (n = 123): nasal cannula oxygen group (Group C), 100% FiO2 of HFNC group (Group H100), and 50% FiO2 of HFNC (Group H50). The primary endpoint in this study was the incidence of hypoxia events with pulse oxygen saturation (SpO2) ≤ 92%. The secondary endpoints included the incidence of other varying degrees of hypoxia and adverse events associated with ventilation and hypoxia. RESULTS: The incidence of hypoxia, paradoxical response, choking, jaw lift, and mask ventilation was lower in both Group H100 and Group H50 than in Group C (P < 0.05). Compared with Group H100, Group H50 showed no significant differences in the incidence of hypoxia, jaw lift and mask ventilation, paradoxical response, or choking (P > 0.05). No patients were mechanically ventilated with endotracheal intubation or found to have complications from HFNC. CONCLUSION: HFNC prevented hypoxia during gastroscopy with propofol in elderly patients, and there was no significant difference in the incidence of hypoxia when FiO2 was 50% or 100%. TRIAL REGISTRATION: This single-blind, prospective, randomized controlled trial was approved by the Ethics Committee of Nanjing First Hospital (KY20201102-04) and registered in the China Clinical Trial Center (20/10/2021, ChiCTR2100052144) before patients enrollment. All patients signed an informed consent form.

Design, synthesis and biological evaluation of novel diazaspirodecanone derivatives containing piperidine-4-carboxamide as chitin synthase inhibitors and antifungal agents.

A series of novel 2-oxo-(1-oxo-2,8-diazaspiro[4.5]decane-8-yl)ethylpiperidine carboxamide derivatives were designed, synthesized and characterized by 1H NMR, 13C NMR and HRMS spectroscopy. All eighteen newly prepared compounds were evaluated for their inhibition against chitin synthase (CHS) and antifungal activities in vitro. The enzyme assay revealed that compound 5h showed excellent inhibitory activity against CHS with IC50 value of 0.10 mM, and the compounds 5b, 5d and 5q showed good inhibition against chitin synthase with IC50 values of 0.13 mM, 0.18 mM and 0.15 mM, respectively, while IC50 value of ployoxin B was 0.08 mM. Meanwhile, the others of these compounds exhibited moderate inhibition potency against chitin synthase. The antifungal assay showed compound 5h had excellent antifungal activity compared with the control drugs fluconazole and polyoxin B against these tested strains including C. albicans, A. fumigatus, C. neoformans and A. flavus. Its excellent antifungal activity was consistent with its excellent chitin synthase inhibition. Compound 5k and 5l against C. albicans were comparable with fluconazole, and they showed strong antifungal potency against A. flavus with MIC values of 0.07 mmol/L and 0.13 mmol/L respectively. Compound 5m had similar MIC value against A. fumigatus to fluconazole. The phenomenon that compounds 5b, 5d and 5q that showed good enzymatic inhibition didn't exert good antifungal activity, while compounds 5k, 5l and 5m that showed moderate chitin synthase inhibition exhibited excellent antifungal activity was discussed. Furthermore, the trial of drug combination showed that compounds had synergistic effects or additive effects with fluconazole against tested fungi which also verified that these designed compounds targeted different targets from that of fluconazole. Additionally, the antibacterial trial showed that all synthesized compounds had little potency against tested bacteria strains. These results indicated that the designed compounds were potential chitin synthase inhibitors and had selectively antifungal activities.

Effect of green tea consumption on human brain function in resting-state functional MRI.

BACKGROUND AND OBJECTIVES: Green tea is reported to have wide benefits on psychological states and cognitive functions. Studies that focus on the underlying neural mechanisms of green tea are limited to its single composition while people usually benefit from green tea water that contains various composition. In this study, we examined the human brain activity changes after drinking natural green tea by using regional homogeneity and functional connectivity based on the resting-state functional MRI technique. METHODS AND STUDY DESIGN: Fifteen healthy volunteers participated in two imaging sessions: a control (water) session and a green tea session, each session comprised a predrinking, drinking, and postdrinking section, during the drinking section, the subject consumed 200 mL of green tea infusion or water in 3 to 5 minutes. Then the post-tea and post-water imaging data were selected for regional homogeneity and functional connectivity analysis. RESULTS: Our results revealed that, compared with the control group, the green tea group exhibited an increased regional homogeneity in the frontal, parietal, and occipital areas of the brain, decreased regional homogeneity values in the left cuneus and left lingual gyrus, mainly a decreased functional connectivity in the default mode network, somatosensory, visual cortex, and parieto-frontal areas and enhanced functional connectivity in brain regions associated with memory. CONCLUSIONS: This result indicates that green tea consumption impacts the brain activity during resting state.

Long noncoding RNA LUCAT1 promotes malignancy of ovarian cancer through regulation of miR-612/HOXA13 pathway.

Emerging evidence shows that long noncoding RNA (lncRNA) is implicated in numerous kinds of malignant cancers, including ovarian cancer. In this study, we focused on the expression and function of long noncoding RNA lung cancer associated transcript 1 (LUCAT1) in ovarian cancer progression. We indicated that LUCAT1 expression was significantly upregulated in ovarian cancer tissues. Moreover, LUCAT1 expression was positively associated with tumor metastasis and clinical stage. Elevated expression of LUCAT1 decreased the survival rate of patients with ovarian cancer. In addition, we revealed that repression of LUCAT1 significantly suppressed the proliferation, migration and invasion, whereas promoted apoptotic rate. Through online predictive tools and functional experiments, we demonstrated that LUCAT1 and HOXA13 were targets of miR-612. We showed that LUCAT1 and miR-612 suppressed each other in a reciprocal way. Moreover, LUCAT1 promoted HOXA13 expression through inhibition of miR-612, eventually leading to ovarian cancer development. In conclusion, our findings revealed a novel molecular mechanism that LUCAT1/miR-612/HOXA13 pathway modulates ovarian cancer progression.

Combination of R-R Interval and Crest Time in Assessing Complexity Using Multiscale Cross-Approximate Entropy in Normal and Diabetic Subjects.

The present study aimed at testing the hypothesis that application of multiscale cross-approximate entropy (MCAE) analysis in the study of nonlinear coupling behavior of two synchronized time series of different natures [i.e., R-R interval (RRI) and crest time (CT, the time interval from foot to peakof a pulse wave)] could yield information on complexity related to diabetes-associated vascular changes. Signals of a single waveform parameter (i.e., CT) from photoplethysmography and RRI from electrocardiogram were simultaneously acquired within a period of one thousand cardiac cycles for the computation of different multiscale entropy indices from healthy young adults (n = 22) (Group 1), upper-middle aged non-diabetic subjects (n = 34) (Group 2) and diabetic patients (n = 34) (Group 3). The demographic (i.e., age), anthropometric (i.e., body height, body weight, waist circumference, body-mass index), hemodynamic (i.e., systolic and diastolic blood pressures), and serum biochemical (i.e., high- and low-density lipoprotein cholesterol, total cholesterol, and triglyceride) parameters were compared with different multiscale entropy indices including small- and large-scale multiscale entropy indices for CT and RRI [MEISS(CT), MEILS(CT), MEISS(RRI), MEILS(RRI), respectively] as well as small- and large-scale multiscale cross-approximate entropy indices [MCEISS, MCEILS, respectively]. The results demonstrated that both MEILS(RRI) and MCEILS significantly differentiated between Group 2 and Group 3 (all p < 0.017). Multivariate linear regression analysis showed significant associations of MEILS(RRI) and MCEILS(RRI,CT) with age and glycated hemoglobin level (all p < 0.017). The findings highlight the successful application of a novel multiscale cross-approximate entropy index in non-invasively identifying diabetes-associated subtle changes in vascular functional integrity, which is of clinical importance in preventive medicine.

Regulation of Sirtuin 3-Mediated Deacetylation of Cyclophilin D Attenuated Cognitive Dysfunction Induced by Sepsis-Associated Encephalopathy in Mice.

The present study aimed to investigate cognitive dysfunction in the hippocampus induced by sepsis-associated encephalopathy (SAE) via acetylation of cyclophilin D (CypD) and opening of mitochondrial permeability transition pore. It also explored whether activating sirtuin 3 (SIRT3) can mediate deacetylation of CypD and prevent the development of SAE. Male mice were randomly assigned to six groups: sham group, cecal ligation puncture group, CypD siRNA transfection (CypD-si) group, CypD control siRNA transfection (CypD-c) group, SIRT3 overexpression vector pcDNA3.1 (SIRT3-p) group, and SIRT3 empty vector pcDNA3.1 (SIRT3-v) group (n = 18). The CypD-si and CypD-c groups were transfected with CypD siRNA and CypD control siRNA, respectively. The SIRT3-p and SIRT3-v groups were injected with SIRT3 pcDNA3.1 and vector pcDNA3.1, respectively. The learning and memory function was assessed using the learning version of the Morris water maze test. Then, cell apoptosis and the levels of CypD, acetylated CypD, SIRT-3, interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and caspase-3 in the hippocampus were determined. The levels of CypD and acetylation of CypD increased in the hippocampus induced by SAE. Increasing SIRT3 and decreasing CypD can attenuate cognitive impairment and neuroapoptosis, and protect the integrity of mitochondrial membrane from damage and restore the protein expressions of IL-6, TNF-α, and caspase-3. Activating SIRT3-mediated deacetylation of CypD attenuated learning and memory dysfunction induced by SAE.

[Mechanisms for the regulatory effect of prostaglandin E2/prostaglandin E receptor 4 on high mobility group box-1 protein in lipopolysaccharide-induced sepsis in mouse peritoneal macrophage].

OBJECTIVE: To explore the effect of prostaglandin E2 (PGE2) on the expression of high mobility group box-1 protein (HMGB1) in peritoneal macrophages of septic mice and its possible mechanisms.
 Methods: The mouse peritoneal macrophages were isolated and cultured by conventional methods.The model of inflammation was established by using lipopolysaccharide (LPS) to incubate with mouse peritoneal macrophages. The PGE2, prostaglandin E receptor (EP) 4 agonist, EP4 RNAi, and DN.CREB inhibitory plasmid were used to interfere with the LPS-treated mouse peritoneal macrophage. The levels of HMGB1 was determined by Western blot.
 Results: Compared with LPS alone treatment, the expression of HMGB1 in peritoneal macrophages was increased obviously after 24 h by treatment with PGE2 and LPS, and it was also increased after the combined treatment of EP4 receptor agonist with LPS for 24 h (both P<0.05); compared with the PGE2+LPS treatment, the level of HMGB1 was decreased after knockdown of EP4 receptor expression (P<0.05); compared with EP4 receptor agonist +LPS treatment, there was no difference in HMGB1 levels in mice after the treatment with DN.CREB plasmid to suppress CREB function (P>0.05); compared with LPS alone treatment, the combined treatment of EP4 receptor agonist with LPS for 24 h could up-regulate the phosphorylation of epidermal growth factor receptor (EGFR) and protein kinase B (Akt) thr308 (P<0.05), which were blocked by EGFR inhibitor. Once Akt specific inhibitor was used before EP4 and LPS treatment, the expression of HMGB1 was declined (P<0.05).
 Conclusion: PGE2 can up-regulate the expression of HMGB1 in sepsis of peritoneal macrophages through EP4 receptor, which may be related to the activation of EGFR/PI3K/Akt signaling pathway.

Notch signal regulates corneal endothelial-to-mesenchymal transition.

Endothelial-to-mesenchymal transition (EnMT) is a cell transformation process involved in both morphogenesis and pathogenesis. EnMT of corneal endothelial cells happens after endothelial injury and during ex vivo culture. Previous studies have shown that the transforming growth factor-ß signaling pathway is involved in this transition. In this study, we found that rat corneal endothelial cells could spontaneously undergo EnMT during ex vivo culture. This change in rat corneal endothelial cells was associated with Notch signaling pathway activation after the first passage, which was blocked by the Notch inhibitor N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT). This inhibitor also prevented transforming growth factor ß1-, ß2-, and ß3-induced EnMT and reversed transformed rat corneal endothelial cells to a normal phenotype. Furthermore, DAPT treatment blocked retrocorneal membrane formation in a rat corneal endothelium damage model. Our study indicates that the Notch signaling pathway is involved in the corneal EnMT process, which may be a novel therapeutic target for treating corneal endothelial fibrogenic disorders.

Gastrodin ameliorates postoperative cognitive dysfunction in aged mice by promoting nuclear translocation of Nrf2 through activation of AMPK.

BACKGROUND: Perioperative neurocognitive disorder (PND) remains a prevalent complication following anesthesia and surgery. Recent studies have revealed the therapeutic potential of gastrodin (GAS) in treating cognitive disturbances. This study delves deeper into the mechanisms through which GAS impacts PND. METHODS: Male C57BL/6 mice (18 months old) underwent laparotomies and were administered GAS orally daily for three weeks preceding surgery and one week post-surgery. Thirty minutes before GAS administration, an intraperitoneal injection of Compound C was given. In vitro, H2O2-incubated SH-SY-5Y cells, with or without Nrf2-siRNA transfection, were set up and subjected to GAS or Compound C treatments. Cell viability was assessed via MTT assays, and apoptosis levels were assessed through flow cytometry. Cognitive function was evaluated using the Morris water maze, novel object recognition, and Y-maze tests. Oxidative stress markers, including MDA, SOD, GSH, GSH-px, and intracellular ROS (determined through immunofluorescence), were quantified. The expression of the genes Caspase3, Bax, Bcl-2, GST, and NQO1 was gauged using real-time RT-PCR. Brain, cortex and hippocampal pathologies were examined with hematoxylin-eosin (HE) and NeuN/TUNEL costaining. Finally, Nrf2 and p-AMPK were analyzed using Western blotting (WB) and immunofluorescence assays. RESULTS: GAS improved cognitive dysfunction in PND mice and reduced oxidative stress, neuro-apoptosis, and ROS levels both in vivo and in vitro experiment. In vivo, Immunofluorescence and Western blot outcomes indicated that postoperative p-AMPK and Nrf2 levels in the hippocampus were mitigated but were augmented by GAS. In vitro studies revealed GAS's protective effect against H2O2-induced oxidative stress and apoptosis and its upregulation of p-AMPK and Nrf2 in SH-SY-5Y cells. Notably, this protective effect was negated when Nrf2 siRNA was introduced. ELISA and PCR results highlighted the role of GAS in enhancing GST and NQO1 activity in both the mice hippocampus and SH-SY-5Y cells. Compound C, an AMPK inhibitor, both in vitro and in vivo, reversed the beneficial effects of GAS on Nuc-Nrf2/Cyt-Nrf2 expression and counteracted the positive influence of GAS on cognitive functions in PND mice. CONCLUSION: GAS facilitates the nuclear translocation of Nrf2 via AMPK activation, offering a therapeutic avenue for alleviating postoperative cognitive impairments in mice, with a significant reduction in oxidative stress.

Effects of stumping on fine root architecture, growth, and physiology of Hippophae rhamnoides.

Background: Fine roots are vital to a plant's ability to absorb water and nutrients. Stumping is a practice that may encourage fine root growth and the rapid recovery of decaying Hippophae rhamnoides plants. However, the effect of stumping on the fine roots and physiological indices is still unknown. The differential indices between stumped forests and non-stumped forests must also be defined. Methods: We recorded the changes in the fine roots of structure H. rhamnoides one year after stumping. Using single factor analysis of variance and general linear models we comprehensively analyzed the number of root tips and the plant's growth and physiological indices in response to stumping. Partial least squares discriminant analysis (PLS-DA) was used to compare fine root growth and physiological indices with and without stumping in order to identify the differential indices. Results: The proportion of root tips in the vertical layers at 30-40 cm and 40-50 cm and in the horizontal layers at 60-80 cm and 80-100 cm, increased after stumping by 1.85%, 2.60%, 1.96% and 4.32%, respectively. In the 0-50 cm soil layer, the fine root dry weight rose by 27.6% compared with the control, which was not significant. However, other indices were significantly different from the control. The proportions in the growth indices in the 30-40 cm and 40-50 cm layers increased after stumping. Stumping had a significant, negative effect on proline and malondialdehyde content, which dropped by 40.95% and 55.32%, respectively, indicating that the harms caused by these two chemicals was alleviated. Stumping had a significant positive effect on root activity and soluble sugar contents, which increased by 68.58% and 36.87%, respectively, and improved the growing ability of fine roots. PLS-DA revealed that malondialdehyde, soluble sugars, root density, and the number of root tips ranked from having the least to greatest effect on the classification of stumping and no-stumping. Conclusions: The process of stumping may promote fine roots growth in H. rhamnoides, and is favorable for their longitudinal development. The fine root growing indices of H. rhamnoides responded positively to this process. Stumping promotes root activity and the creation of soluble sugar to maintain the growth and development of fine roots. It also inhibits the negative effects of proline and malondialdehyde on fine roots. Our study showed that the differential physiological indices were more important for classification than the differential growing indices.

Research of integrated shimming Halbach magnet for High strength, compact Benchtop NMR device.

Due to production and assembly errors of magnets resulting in reduced magnetic field homogeneity, passive shimming (PS) is necessary when Halbach magnets are used in high-resolution Benchtop Nuclear Magnetic Resonance (BNMR) spectrometer. The conventional PS technique, which places independent PS devices inside the magnet aperture, is no longer applicable to small-aperture compact high-field-strength Halbach magnet studies. In this paper, based on spherical harmonic function expansion, we improve the magnetic field homogeneity by optimizing the moving step of the magnet moving arrays composed of Halbach magnets to generate the corresponding harmonic terms to compensate for the magnetic field. With this approach, the homogeneity of a 1 T Halbach magnet was improved from the original 3913 ppm to 8 ppm in a L10 mm × R2.5 mm of 0.64% copper sulfate doped water sample. This work explores the PS mechanism based on the movement of magnetic blocks, which can be applied in BNMR and other compact high-field strength high-homogeneity Halbach magnets application circumstances.

Novel spiro[pyrrolidine-2,3'-quinoline]-2'-one derivatives containing piperazine fragment as potential chitin synthase inhibitors and antifungal agents: Design, synthesis and biological evaluation.

A series of spiro[pyrrolidine-2,3'-quinoline]-2'-one derivatives were designed and synthesized for the discovery of novel antifungal drugs. The bioactivities of all derivatives were screened by evaluating their inhibitory effects against chitin synthase (CHS) and antimicrobial activities in vitro. Enzyme inhibition experiments showed that all the synthesized compounds inhibited the chitin synthase. Compounds 4d, 4k, 4n and 4o showed inhibitory effects against CHS with IC50 values which were close to that of the control drug (polyoxin B). The results of enzyme kinetics experiment showed that these compounds were non-competitive inhibitors of chitin synthase (Ki of compound 4o is 0.14 mM). Antimicrobial experiments showed that these compounds exhibited moderate to excellent antifungal activity against pathogenic fungal strains while the compounds showed little potency against bacteria. Among them, compounds 4d, 4f, 4k and 4n showed stronger antifungal activities against C. albicans than those of fluconazole and polyoxin B. Compounds 4f, 4n and 4o showed better antifungal activities against A. flavus than those of fluconazole and polyoxin B. Compound 4d showed similar activity to that of fluconazole and stronger activity than those of polyoxin B against C. neoformans and A. fumigatus. It is also showed that these compounds have the potency against drug-resistant fungal variants. The results of sorbitol protection assay and evaluation of antifungal activity against micafungin-resistant strains experiment further illustrated that these compounds inhibited the synthesis of chitin of fungal cell wall. Drug combination experiments showed that these compounds had synergistic or additive effects when combined with fluconazole or polyoxin B. The synergistic effects with polyoxin B further confirmed the compounds were non-competitive inhibitors of chitin synthase. Additionally, docking studies showed that these compounds had strong affinity with chitin synthase from C. albicans (CaChs2). These results indicate that the target of these synthesized compounds is chitin synthase, and these compounds had excellent antifungal activity while possessed the potency against drug-resistant fungal variants.