Nicotine perturbs the microbiota of brown planthopper (Nilaparvata lugens stål Hemiptera: Delphinidae).

Bacterial symbionts exhibiting co-evolutionary patterns with insect hosts play a vital role in the nutrient synthesis, metabolism, development, reproduction, and immunity of insects. The brown planthopper (BPH) has a strong ability to adapt to various environmental stresses and can develop resistance to broad-spectrum insecticides. We aimed to investigate whether gut symbionts of BPH play a major role in the detoxification of insecticides and host fitness in unfavorable environments. Nicotine-treated rice plants were exposed to BPH (early stage) and the gut microbiome of the emerging female adults were analyzed using high throughput sequencing (HTS). Nicotine administration altered the diversity and community structure of BPH symbionts with significant increases in bacterial members such as Microbacteriaceae, Comamondaceae, Enterobacteriaceae, and these changes may be associated with host survival strategies in adverse environments. Furthermore, the in-vitro study showed that four intestinal bacterial strains of BPH (Enterobacter NLB1, Bacillus cereus NL1, Ralstonia NLG26, and Delftia NLG11) could degrade nicotine when grown in a nicotine-containing medium, with the highest degradation (71%) observed in Delftia NLG11. RT-qPCR and ELISA analysis revealed an increased expression level of CYP6AY1 and P450 enzyme activities in Delftia NLG11, respectively. CYP6AY1 increased by 20% under the action of Delftia and nicotine, while P450 enzyme activity increased by 18.1%. After CYP6AY1 interference, nicotine tolerance decreased, and the mortality rate reached 76.65% on the first day and 100% on the third day. Moreover, Delftia NLG11 helped axenic BPHs to increase their survival rate when fed nicotine in the liquid-diet sac (LDS) feeding system. Compared with axenic BPHs, the survival rate improved by 25.11% on day 2% and 6.67% on day 3. These results revealed an altered gut microbiota and a cooperative relationship between Delftia NLG11 and CYP6AY1 in nicotine-treated BPH, suggesting that insects can adapt to a hostile environment by interacting with their symbionts and providing a new idea for integrated pest management strategies.

Salidroside attenuates HALI via IL-17A-mediated ferroptosis of alveolar epithelial cells by regulating Act1-TRAF6-p38 MAPK pathway.

BACKGROUND AND PURPOSE: Hyperoxia-induced acute lung injury (HALI) is a critical life-threatening disorder characterized by severe infiltration immune cells and death of type II alveolar epithelial cells (AECII). However, little is known about the relations between immune cells and AECII in HALI. IL-17A is a pro-inflammatory cytokine mainly secreted by Th17 cells, contributing to the pathogenesis of various inflammatory diseases. The present study investigated the role of IL-17A in cell-cell communication between immune cells and AECII in HALI, and explored the therapeutic effect of salidroside (Sal, a natural anti-inflammatory agents) on HALI. METHODS: Mice with HALI were induced by exposure to hyperoxia over 90% for 12 h, 24 h, 48 h or 72 h, and the optimal timing was detected by H&E and Masson staining. Ferroptosis was confirmed by detecting the levels of MDA, Fe2+ and GPX4, and the morphological alterations of AECII under transmission electron microscopy. The expression of pro-inflammatory cytokine, including IL-6, TGF-ß1, IL-17A and IL-17A receptor (IL-17RA) were measured by Western blotting and immunohistochemical stanning. The ferroptosis-related Act1/TRAF6/p38 MAPK pathway was detected by Western blotting. The role of pro-inflammatory cytokine IL-17A for AECII ferroptosis, and the effect of Sal on HALI were investigated by administration of Y-320 (IL-17 inhibitor) and Sal respectively 3 days before mice exposed to hyperoxia. RESULTS: Mice exposed to hyperoxia for 24 h suffered sufficient HALI with inflammatory cell infiltration and collagen deposition, and exhibited features of ferroptosis under TME. Meanwhile, compared with sham mice, mice exposed to hyperoxia showed down-regulation of GPX4, and up-regulation of IL-6, TGF-ß1, IL-17A, IL-17RA, Act1, TRAF6, p38 MAPK and p-p38 MAPK. Moreover, inhibition of IL-17A with Y-320 or administration with Sal could reverse the effect caused by hyperoxia respectively. CONCLUSIONS: IL-17A is associated with immune cells infiltration in HALI, and contributes to ferroptosis of AECII that related to Act1/TRAF6/p38 MAPK pathway. Additionally, Sal protects against HALI throughout the whole pathogenic process. Video Abstract.

Oxygen inhalation has been widely used in the treatment of some diseases caused by hypoxia. This often leads people to mistakenly believe that oxygen inhalation is beneficial without harm. However, long-term high concentration oxygen inhalation will cause serious harm to the human body, sometimes even fatal. Hyperoxia causes lung cells to secrete proinflammatory factors, which promote the differentiation of infiltrated immune cells. The differentiated immune cells in turn act on lung cells and lead to their death. In short, this process is a vicious circle. Our research explores this process and is committed to finding a drug to reduce the damage of hyperoxia to the lungs when oxygen must be inhaled.

Repeated Preoperative Intranasal Administration of Insulin Decreases the Incidence of Postoperative Delirium in Elderly Patients Undergoing Laparoscopic Radical Gastrointestinal Surgery: A Randomized, Placebo-Controlled, Double-Blinded Clinical Study.

STUDY OBJECTIVES: This study aimed to investigate the effects of repeated preoperative intranasal administration of insulin on the incidence of postoperative delirium (POD) and the levels of serum pro-inflammatory markers in elderly patients undergoing laparoscopic radical gastrointestinal surgery. DESIGN: Prospective, randomized, double-blinded, placebo-controlled clinical study. SETTING: General Hospital of Western Theater Command from August 2019 to December 2019. PATIENTS: Ninety elderly patients underwent laparoscopic radical gastrointestinal tumor resections under general anesthesia. INTERVENTIONS: Patients were randomly divided into a control group (0.5 mL saline administered intranasally) or an insulin group (20 U/0.5 mL insulin administered intranasally) for 2 days prior to surgery, with 45 patients in each group. MEASUREMENTS: The incidence of delirium was measured at postoperative day 1 (T2), day 3 (T3), and day 5 (T4) using the Confusion Assessment Method for the intensive care unit (CAM-ICU). Plasma levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α were measured at T0 (before insulin or saline administration), T1 (at the end of surgery), T2, T3, and T4 by enzyme-linked immunosorbent assay. MAIN RESULTS: Compared with the control group, the insulin group demonstrated a decreased POD incidence (12.5% vs. 47.5%, p = 0.001) within 5 days after surgery. The incidence of POD was significantly lower in the Ins group than in the Con group at T2 (12.5% vs. 32.5%, p = 0.032) and at T3 (2.5% vs. 20%, p = 0.034). The incidence of POD decreased in both groups over time and was similar at T4 (0% vs 10%, p = 0.116). Compared with the baseline value at T0, serum TNF-α, IL-6 and IL-1ß concentrations increased significantly at T1-4 (p <0.05). Compared with the control group at the same time point, the expression levels of TNF-α, IL-6 and IL-1ß in group I at T2 and T3 were significantly reduced (p <0.05). The incidence rates of adverse events were similar in the two groups. CONCLUSIONS: Repeated preoperative intranasal administration of insulin prevented the occurrence of delirium after laparoscopic radical gastrointestinal surgery in elderly patients and reduced TNF-α, IL-1ß, and IL-6 levels.

Carbon Monoxide-Saturated Hemoglobin-Based Oxygen Carriers Attenuate High-Altitude-Induced Cardiac Injury by Amelioration of the Inflammation Response and Mitochondrial Oxidative Damage.

OBJECTIVE: To investigate the therapeutic effect of carbon monoxide (CO) on high-altitude hypoxia-induced cardiac damage. METHODS: Forty male C57BL/6 mice were randomly divided into 4 groups. The mice were exposed to normoxia or simulated 5,500-meter high-altitude hypoxia in a hypobaric chamber for 7 days. During the first 3 days, the mice were pretreated with CO-saturated hemoglobin (Hb)-based oxygen carrier (CO-HBOC), oxygen-saturated hemoglobin-based oxygen carrier (O2-HBOC) at a dose of 0.3 g Hb/kg/day or an equivalent volume of saline. The in vivo left ventricle function, cardiac enzyme release, histopathological changes, apoptosis and inflammation were also measured. RESULTS: High-altitude hypoxia induced significant cardiac damage, as demonstrated by impaired cardiac function and increased proapoptotic, proinflammatory and pro-oxidant markers. Pretreatment with CO-HBOC significantly improved cardiac performance, reduced cardiac enzyme release and limited myocardial apoptosis. The increased inflammatory response was also suppressed. In addition to the preserved mitochondrial structure, hypobaric hypoxia-induced mitochondrial oxidative damage was remarkably attenuated. Moreover, these antiapoptotic and antioxidative effects were accompanied by an upregulated phosphorylation of Akt, ERK and STAT3. CONCLUSION: This study demonstrated that CO-HBOC provides a promising protective effect on high-altitude hypoxia-induced myocardial injury, which is mediated by the inhibition of inflammation and mitochondrial oxidative damage.

Common variants in SIRT1 and human longevity in a Chinese population.

BACKGROUND: The silent information regulator SIR2/SIRT1gene has been demonstrated as regulating lifespan in many model organisms, including yeast, worms, fruit flies and rodents. SIRT1, the human homolog of SIR2, is considered a candidate gene as a modifier of human life expectancy. METHODS: In the current study we included 616 long-lived individuals and 846 matched younger controls to investigate associations between 8 common single nucleotide polymorphisms (SNPs) (i.e., rs12778366, rs3758391, rs3740051, rs33957861, rs7896005, rs12413112, rs11599176 and rs4746720) in the SIRT1 gene and human longevity. RESULTS: The 8 SNPs had strong linkage disequilibrium (LD) and were in an LD block, which was characterized by 4 common haplotypes that capture 99.3% of the genetic variation present within it. We found no evidence for statistically significant associations between the tested SIRT1 SNPs and longevity at the allele, genotype or haplotype levels. CONCLUSIONS: Current findings show that several common variants in SIRT1 are not associated with human longevity.

Association of common variants in TOMM40/APOE/APOC1 region with human longevity in a Chinese population.

Apolipoprotein E (APOE), translocase of outer mitochondrial membrane 40 homolog (TOMM40) and apolipoprotein C-I (APOC1) may extend lifespan by marked delay or escape from age-related diseases. This study aimed to elucidate the association of human longevity with genetic variations in TOMM40/APOE/APOC1 region in a Chinese population. Ten tag single-nucleotide polymorphisms (SNPs) in the TOMM40/APOE/APOC1 region were successfully genotyped in 616 unrelated long-lived individuals and 846 younger controls. Of the 10 SNPs, rs7254892 in 5' upstream of TOMM40 showed significant association with human longevity (G/A-A/A vs G/G: odds ratio (OR)=1.59, 95% confidence interval (CI)=1.20-2.09, P=0.0011, Bonferroni corrected P (Pc)=0.033). The haplotype analysis suggested that individuals carrying the haplotype A-A-A-A-T-A-T-G-C-A (rs7254892-rs157580-rs2075649-rs2075650-rs157582-rs8106922-rs1160985-rs405697-rs439401-rs445925) tended to have longer lifespan than those carrying the most common haplotype G-G-A-A-C-A-C-A-T-G (OR=1.59, 95% CI=1.19-2.12, P=0.0018, Pc=0.0216). These findings indicated that variants in TOMM40/APOE/APOC1 region might be associated with human longevity. Further studies are needed to identify the causal genetic variants influencing human longevity.

Lack of association between polymorphisms in the SIRT6 gene and longevity in a Chinese population.

Sirtuin 6 (SIRT6) has recently been demonstrated to play an important role in the regulation of longevity in mammals. We therefore aimed to determine whether common variations in the SIRT6 gene are associated with human longevity. Five tag single nucleotide polymorphisms (SNPs) across the SIRT6 gene and its 5 kb up-/downstream region, including rs350852, rs350844, rs352493, rs4807546 and rs3760905, have been successfully determined in 616 unrelated Chinese long-lived individuals (LLIs) (mean age: 102.4 ± 2.3 years) and 846 younger controls (mean age: 48.9 ± 10.6 years) from Hainan Island, China. The allele and genotype frequencies of the five SNPs showed no statistically significant difference between the LLIs and controls (all P > 0.05). The five SNPs were in strong linkage disequilibrium and defined seven common haplotypes. Likewise, no association between these haplotypes and longevity was observed (all P > 0.05). The present study reveals that common genetic variations in the SIRT6 gene are not associated with human longevity.

Development of highly sensitive sensor system for methane utilizing cataluminescence.

A gaseous sensor system was developed for the detection of methane based on its cataluminescence emission. Cataluminescence characteristics and optimal conditions were studied in detail under optimized experimental conditions. Results showed that the methane cataluminescence sensor system could cover a linear detection range from 10 to 5800 ppm (R = 0.9963, n = 7) and the detection limit was about 7 ppm (S/N = 3), which was below the standard permitted concentration. Moreover, a linear discriminant analysis method was used to test the recognizable performance of the methane sensor. It was found that methane, ethane, propane and pentane could be distinguished clearly. Its methane sensing properties, including improved sensitivity, selectivity, stability and recognition demonstrated the TiO2/SnO2 materials to be promising candidates for constructing a cataluminescence-based gas sensor that could be used for detecting explosive gas contaminants.

[The Protective Effect of Tanshinone IIA on Oxygen-glucose Deprivation and Reperfusion Injury of MicrogliaThrough the NLRP3 Inflammatory Signaling Pathway].

OBJECTIVES: To investigate the protective effect of Tanshinone IIA (TSA) on oxygen-glucose deprivation and reperfusion (OGD/R) injury of BV-2 cell and its NLRP3 inflammatory signaling pathway. METHODS: The highest expression level of NLPR3 in BV-2 cells was detected by Western blot after oxygen-glucose deprivation (OGD) for 3 h and reperfusion for different time, to determine the most suitable reperfusion time. Cell viability of TSA (0-2.5 ug/mL) treatment was detected by CCK8 assay to determine the maximum effect concentration of TSA. In TSA 0 (also called OGD group), 0.5, 1.0, 2.0 ug/mL groups, expression levels of NLRP3 and caspase-1 were detected by Western blot, while IL-1ß and IL-18 in culture medium of those groups were detected by ELISA assay. RESULTS: The highest expression level of NLRP3 came to 12 h of reperfusion. The maximum effective concentration of TSA was 2.0 ug/mL. The expression levels of NLRP3, caspase-1, IL-1ß and IL-18 decreased with the increase of TSA concentration. CONCLUSIONS: TSA can inhibit the expression of protein and cytokines of NLRP3 inflammatory signaling pathway in OGD/R BV-2 cells, which may be one of the molecular mechanisms of the protective effect of TSA on OGD/R cells.

Humid heat exposure induced oxidative stress and apoptosis in cardiomyocytes through the angiotensin II signaling pathway.

Exposure to humid heat stress leads to the initiation of serious physiological dysfunction that may result in heat-related diseases, including heat stroke, heat cramp, heat exhaustion, and even death. Increasing evidences have shown that the humid heat stress-induced dysfunction of the cardiovascular system was accompanied with severe cardiomyocyte injury; however, the precise mechanism of heat stress-induced injury of cardiomyocyte remains unknown. In the present study, we hypothesized that humid heat stress promoted oxidative stress through the activation of angiotensin II (Ang II) in cardiomyocytes. To test our hypothesis, we established mouse models of humid heat stress. Using the animal models, we found that Ang II levels in serum were significantly up-regulated and that the Ang II receptor AT1 was increased in cardiomyocytes. The antioxidant ability in plasma and heart tissues which was detected by the ferric reducing/antioxidant power assay was also decreased with the increased ROS production under humid heat stress, as was the expression of antioxidant genes (SOD2, HO-1, GPx). Furthermore, we demonstrated that the Ang II receptor antagonist, valsartan, effectively relieved oxidative stress, blocked Ang II signaling pathway and suppressed cardiomyocyte apoptosis induced by humid heat stress. In addition, overexpression of antioxidant genes reversed cardiomyocyte apoptosis induced by Ang II. Overall, these results implied that humid heat stress increased oxidative stress and caused apoptosis of cardiomyocytes through the Ang II signaling pathway. Thus, targeting the Ang II signaling pathway may provide a promising approach for the prevention and treatment of cardiovascular diseases caused by humid heat stress.

Effects of Intranasal Insulin Pretreatment on Preoperative Sleep Quality and Postoperative Delirium in Patients Undergoing Valve Replacement for Rheumatic Heart Disease.

Background: Postoperative delirium (POD) is a common neurological complication associated with valve replacement. Preoperative sleep disturbance is a risk factor for POD development, and nasal insulin modulates the sleep-wake cycle. This study investigated the beneficial effects of intranasal insulin pretreatment on preoperative sleep quality and reducing POD in patients undergoing valve replacement for rheumatic heart disease. Patients and Methods: This prospective, single-center, randomized controlled trial (RCT) included 76 adult patients aged 18-65 years undergoing valve surgery with cardiopulmonary bypass who were randomly allocated to receive intranasal insulin or normal saline interventions two days before surgery. POD incidence was on postoperative days 1 (T3), 2 (T4), and 3 (T5). Before the first intervention (T0), 1 d before surgery (T1), and before anesthesia on the day of surgery (T2), sleep quality was assessed and serum cortisol concentrations were measured. At T1 and T2, sleep quality related indicators monitored by sleep monitoring watches from the previous night were recorded. Results: Compared with the normal saline group, 3 days after surgery, the insulin group showed a significantly reduced incidence of POD; significantly increased deep sleep, REM sleep, deep sleep continuity, and total sleep quality scores at T1 and T2; and significantly reduced serum cortisol concentration, PSQI scale, light sleep ratio, and wakefulness at T1 and T2. Conclusion: The administration of 20 U of intranasal insulin twice daily, from 2 days preoperatively until 10 minutes preanesthesia on the day of surgery, can improved preoperative sleep quality significantly and reduced POD incidence in patients with rheumatic heart disease undergoing valve replacement. Clinical Trial Registration: This study was registered with the Chinese Clinical Trial Registry (www.chictr.org.cn, with the unique identifier ChiCTR2100048515; July 9, 2021).

Puerarin attenuates remifentanil­induced postoperative hyperalgesia via targeting PAX6 to regulate the transcription of TRPV1.

Remifentanil­induced hyperalgesia (RIH) is characterized by the emergence of stimulation­induced pain, including phenomena such as allodynia and thermal hyperalgesia following remifentanil infusion. As a sequence­specific DNA binding transcription factor, PAX6 positively and negatively regulates transcription and is expressed in multiple cell types in the developing and adult central nervous system. It was hypothesized that puerarin could relieve RIH via targeting PAX6 to regulate transcription of transient receptor potential cation channel subfamily V Member 1 (TRPV1). A total of 32 rats were randomly divided into five groups, namely control group, RI group, RI + 10 mg/kg puerarin group (RI + puerarin10), RI + 20 mg/kg puerarin group (RI + puerarin20), and RI + 40 mg/kg puerarin group (RI + puerarin40). Mechanical and thermal hyperalgesia were tested at ­24, 2, 6, 24 and 48 h after remifentanil infusion. Following the sacrifice of rats after the last behavioral test, western blot was used to detect the expression levels of TRPV1 in the tissues; Immunofluorescence staining and western blotting were used to detect the expression of PAX6 in the spinal cord. PharmMapper and JASPAR were used to predict the binding sites of puerarin/PAX6/TRPV1. Chromatin immunoprecipitation­PCR and dual luciferase reporter assay were used to verify the targeting relationship between PAX6 and TRPV1. Immunofluorescence was used to detect the expression levels of TRPV1 and p­NR2B. The results revealed that puerarin (10, 20, 40 mg/kg) dose­dependently reduced thermal and mechanical hyperalgesia from 2 to 48 h after remifentanil infusion. Remifentanil infusion remarkably stimulated the expression of phosphorylated (p­)NR2B. Nevertheless, the increased amount of p­NR2B by RIH was dose­dependently suppressed by puerarin in rats. In conclusion, puerarin was revealed to attenuate postoperative RIH via targeting PAX6 to regulate the transcription of TRPV1.

Extraction, purification, structural characteristics and biological properties of the polysaccharides from Armillaria mellea (Vahl) P. Kumm.: A review.

Armillaria mellea (Vahl) P. Kumm. is a well-known homoeopathic plant with medicinal and culinary uses. Modern phytochemical researchers have successfully extracted and purified over 40 types of A. mellea polysaccharides (AMPs) from the fruiting bodies, hyphae and fermentation broth of A. mellea, and some of them have been analyzed and identified by their chemical structures. The impressive biological activity of these polysaccharides has been recognized by scientists worldwide. Many studies show that AMPs have remarkable antioxidant, anti-diabetic, anti-tumor, anti-inflammatory, immunoregulatory, hypolipidemic, thrombectomy, anti-aging, pulmonary protective, hepatic protective, anti-Alzheimer's properties, etc. However, the current understanding of the relationships between their chemical structure and biological activity, toxicological effects and pharmacokinetics remains limited. This article provides a systematic review of the research conducted over the past decades on the extraction and purification methods, structural characteristics, biological activity and mechanism of action of AMPs. The aim is to provide a research base that will benefit the future application of AMPs as therapeutic drugs and functional foods, and also provide insights for the further development of AMPs.

Naked cuticle homolog 1 prevents mouse pulmonary arterial hypertension via inhibition of Wnt/ß-catenin and oxidative stress.

Pulmonary arterial hypertension (PAH) is a poorly prognostic cardiopulmonary disease characterized by abnormal contraction and remodeling of pulmonary artery (PA). Excessive proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) are considered as the major etiology of PA remodeling. As a negative regulator of Wnt/ß-catenin pathway, naked cuticle homolog 1 (NKD1) is originally involved in the tumor growth and metastasis via affecting the proliferation and migration of different types of cancer cells. However, the effect of NKD1 on PAH development has not been investigated. In the current study, downregulated NKD1 was identified in hypoxia-challenged PASMCs. NKD1 overexpression by adenovirus carrying vector encoding Nkd1 (Ad-Nkd1) repressed hypoxia-induced proliferation and migration of PASMCs. Mechanistically, upregulating NKD1 inhibited excessive reactive oxygen species (ROS) generation and ß-catenin expression in PASMCs after hypoxia stimulus. Both inducing ROS and recovering ß-catenin expression abolished NKD1-mediated suppression of proliferation and migration in PASMCs. In vivo, we also observed decreased expression of NKD1 in dissected PAs of monocrotaline (MCT)-induced PAH model. Upregulating NKD1 by Ad-Nkd1 transfection attenuated the increase in right ventricular systolic pressure (RVSP), right ventricular hypertrophy index (RVHI), pulmonary vascular wall thickening, and vascular ß-catenin expression after MCT treatment. After recovering ß-catenin expression by SKL2001, the vascular protection of external expression of NKD1 was also abolished. Taken together, our data suggest that NKD1 inhibits the proliferation, migration of PASMC, and PAH via inhibition of ß-catenin and oxidative stress. Thus, targeting NKD1 may provide novel insights into the prevention and treatment of PAH.

Research progress in brain-targeted nasal drug delivery.

The unique anatomical and physiological connections between the nasal cavity and brain provide a pathway for bypassing the blood-brain barrier to allow for direct brain-targeted drug delivery through nasal administration. There are several advantages of nasal administration compared with other routes; for example, the first-pass effect that leads to the metabolism of orally administered drugs can be bypassed, and the poor compliance associated with injections can be minimized. Nasal administration can also help maximize brain-targeted drug delivery, allowing for high pharmacological activity at lower drug dosages, thereby minimizing the likelihood of adverse effects and providing a highly promising drug delivery pathway for the treatment of central nervous system diseases. The aim of this review article was to briefly describe the physiological structures of the nasal cavity and brain, the pathways through which drugs can enter the brain through the nose, the factors affecting brain-targeted nasal drug delivery, methods to improve brain-targeted nasal drug delivery systems through the application of related biomaterials, common experimental methods used in intranasal drug delivery research, and the current limitations of such approaches, providing a solid foundation for further in-depth research on intranasal brain-targeted drug delivery systems (see Graphical Abstract).

USP18 overexpression protects against spinal cord ischemia/reperfusion injury via regulating autophagy.

BACKGROUND: Spinal cord ischemia-reperfusion injury (SCII) is usually caused by spinal surgery, often leading to severe neurological deficits. The ubiquitin-specific protease 18 (USP18) plays a significant role in neurological diseases. OBJECTIVE: The present study was designed to assess the effects and mechanisms of USP18 on SCII. METHODS: By inducing transient aortic occlusion and subsequent reperfusion, a rat model of SCII was successfully established. The Basso-Beattie-Bresnahan scores, the inclined plane test, and hematoxylin and eosin (HE) were used to measure locomotor activity and histological changes in the injured spinal cords. Moreover, the SCII cell model was established using PC12 cells under oxygen-glucose deprivation and reoxygenation (OGD/R). Proinflammatory factors (TNF-α, IL-6, and INF-α) were examined using an ELISA kit. Cell apoptosis was assessed by Annexin V-FITC/PI double-staining and TUNEL assays. Western blot was used to detect the expression levels of proteins related to apoptosis and autophagy. RESULTS: USP18 expression was decreasedin vivo and in vitro SCII models. The upregulation of USP18 ameliorated hind limbs' motor function, inhibiting inflammation and apoptosis after SCII in rats. USP18 overexpression in vitro may protect PC12 cells from OGD/R-induced damage by modulating inflammatory responses and apoptosis. Moreover, Overexpression of USP18 enhanced autophagy to inhibit cell apoptosis induced by SCII in vivo and in vitro. CONCLUSIONS: In summary, USP18 overexpression protects against SCII via regulating autophagy.

Effect of Repeated Intranasal Administration of Different Doses of Insulin on Postoperative Delirium, Serum τ and Aß Protein in Elderly Patients Undergoing Radical Esophageal Cancer Surgery.

Objective: Postoperative delirium is common after general anesthesia in older patients. However, there are currently no effective preventive measures. This study investigated the effect of repeated intranasal administration of different insulin doses before surgery on postoperative delirium in older patients with esophageal cancer, and the possible mechanism for its efficacy. Methods: In this randomized, placebo-controlled, double-blind, parallel-group study, 90 older patients were randomly assigned to either a Control (normal saline), Insulin 1 (20 U/0.5 mL intranasal insulin), or Insulin 2 (30 U/0.75 mL intranasal insulin) group. Delirium was assessed on postoperative days 1 (T2), 2 (T3), and 3 (T4) using the Confusion Assessment Method for the Intensive Care Unit. Serum τ and Aß protein levels were measured at T0 (before insulin/saline administration), T1 (end of surgery), T2, T3 and T4. Results: The Insulin 2 group had a significantly lower prevalence of delirium compared to the Control and Insulin 1 groups three days after surgery. Compared to baseline, τ and Aß protein levels increased significantly at T1-T4. Compared to the Control group, the Insulin 1 and 2 groups had significantly lower τ and Aß protein levels at T1-T4, and the Insulin 2 group had significantly lower levels than the Insulin 1 group at T1-T2. Conclusion: The administration of 30 U of intranasal insulin twice daily, from 2 days preoperatively until 10 minutes preanesthesia on the day of surgery, can significantly reduce postoperative delirium in older patients undergoing radical esophagectomy. It can also decrease postoperative τ and Aß protein expression without causing hypoglycemia. Clinical Trial Registration: This study was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn, with the unique identifier: ChiCTR2100054245; December 11, 2021).

Design and synthesis of ligustrazine derivatives as potential anti-Alzheimer's agents.

A novel series of ligustrazine derivatives was designed, synthesized, and evaluated as acetylcholinesterase (AChE) and butylcholinesterase (BuChE) inhibitors for the treatment of Alzheimer's disease (AD). In vitro studies displayed that some of the synthesized compounds revealed promising AChE and BuChE inhibitory effects. Particularly, compounds E12 and E27, indicated highly AChE inhibitory activity with IC50 values of 1.85 µM and 0.98 µM, respectively and showed noteworthy protective effects against on glutamate-induced SH-SY5Y cells damage at 1 µM and 10 µM concentrations. Furthermore, molecular simulation docking elucidates compounds E12 and E27 interacting with residues in the binding site of AChE (PDB code: 4EY7) and BuChE (PDB code: 1P0I), emphasizing the protein residues that participate in the main interactions with the two targets. Taken together, these results revealed that compounds E12 and E27 might be potential lead compounds for further structure optimization in the drug-discovery process against AD.

Administration of combined spinal epidural anesthesia with ultrasound-assisted positioning in obese patients undergoing open hysterectomy: A randomized controlled trial.

BACKGROUND: Administration of combined spinal epidural anesthesia (CSEA) with traditional landmark-guided positioning can be challenging in patients with high body mass index (BMI). The popularization of ultrasound technology may effectively solve these problems. However, reports on the administration of CSEA ultrasound-assisted positioning in obese populations are relatively limited and have made inconsistent conclusions. We aimed to investigate the ability of ultrasound-assisted positioning to improve the success rate of CSEA in obese patients. METHODS: Overall, 118 adult women with a BMI ≥ 30 kg/m2 who scheduled to undergo open hysterectomy and received CSEA were recruited. Finally, 108 patients were enrolled and randomly assigned to 2 groups: the ultrasound-assisted positioning group (group A) and traditional landmark-guided positioning group (group B). Ultrasound-assisted or landmark-guided positioning was employed to locate the puncture interspace before anesthesia. The primary outcomes were the success rate of first attempt and number of attempts. The secondary outcomes were the patient positioning accuracy, positioning time, CSEA operation time, patient-satisfaction scores, anesthesia characteristics, and complications of CSEA. RESULTS: The success rate of patient first puncture attempt in group A was significantly higher than that in group B (78.4% vs 52.9%, P = .007). The total number of punctures was lower in group A than that in groups B (average rank 44.54 vs 58.46, P = .005). Using ultrasound positioning as the gold standard, the accuracy of landmark-guided location was only 67%. Positioning time in croup A was longer in group A than that in group B (P = .004), while CSEA operation time spent in Group A was less than that in Group B (P < .001). Patient satisfaction score in group A was significantly higher than that in group B (P = .002). The successful puncture interspace in group A were more likely at L3-4 than that in group B (P = .02). CONCLUSION: The success rate of first puncture attempt and positioning accuracy in CSEA with ultrasound-assisted is significantly higher than those based on landmark-guided location in obese patients.

Glycyrrhizin attenuates rat ischemic spinal cord injury by suppressing inflammatory cytokines and HMGB1.

AIM: To investigate the neuroprotective effect of glycyrrhizin (Gly) against the ischemic injury of rat spinal cord and the possible role of the nuclear protein high-mobility group box 1 (HMGB1) in the process. METHODS: Male Sprague-Dawley rats were subjected to 45 min aortic occlusion to induce transient lumbar spinal cord ischemia. The motor functions of the animals were assessed according to the modified Tarlov scale. The animals were sacrificed 72 h after reperfusion and the lumbar spinal cord segment (L2-L4) was taken out for histopathological examination and Western blotting analysis. Serum inflammatory cytokine and HMGB1 levels were analyzed using ELISA. RESULTS: Gly (6 mg/kg) administered intravenously 30 min before inducing the transient lumbar spinal cord ischemia significantly improved the hind-limb motor function scores, and reduced the number of apoptotic neurons, which was accompanied by reduced levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) in the plasma and injured spinal cord. Moreover, the serum HMGB1 level correlated well with the serum TNF-α, IL-1ß and IL-6 levels during the time period of reperfusion. CONCLUSION: The results suggest that Gly can attenuate the transient spinal cord ischemic injury in rats via reducing inflammatory cytokines and inhibiting the release of HMGB1.