Molecular identification of carboxylesterase genes and their potential roles in the insecticides susceptibility of Grapholita molesta.

Grapholita molesta is one of the most damaging pests worldwide in stone and pome fruits. Application of chemical pesticides is still the main method to control this pest, which results in resistance to several types of insecticides. Carboxylesterase (CarE) is one of the important enzymes involved in the detoxification metabolism and tolerance of xenobiotics and insecticides. However, the roles of CarEs in insecticides susceptibility of G. molesta are still unclear. In the present study, the enzyme activity of CarEs and the mRNA expression of six CarE genes were consistently elevated after treatment with three insecticides (emamectin benzoate, lambda-cyhalothrin, and chlorantraniliprole). According to spatio-temporal expression profiles, six CarE genes expressed differently in different developmental stages, and highly expressed in some detoxification metabolic organs. RNAi-mediated knockdown of these six CarE genes indicated that the susceptibility of G. molesta to all these three insecticides were obviously raised after GmCarE9, GmCarE14, GmCarE16, and GmCarE22 knockdown, respectively. Overall, these results demonstrated that GmCarE9, GmCarE14, GmCarE16, and GmCarE22 play a role in the susceptibility of G. molesta to emamectin benzoate, lambda-cyhalothrin, and chlorantraniliprole treatment. This study expands our understanding of CarEs in insects, that the same CarE gene could participate in the susceptibility to different insecticides.

Therapeutic effects of curcumin liposomes and nanocrystals on inflammatory osteolysis: In vitro and in vivo comparative study.

Curcumin could inhibit periprosthetic osteolysis induced by wear debris and adherent endotoxin, which commonly cause prosthesis loosening and negatively influence the long-term survival of joint arthroplasty. However, its limited water solubility and poor stability pose challenges for its further clinical application. To address these issues, we developed curcumin liposomes for intraarticular injection, as liposomes possess good lubricant capacity and pharmacological synergy with curcumin. Additionally, a nanocrystal dosage form was prepared to enable comparison with the liposomes based on their ability to disperse curcumin effectively. A microfluidic method was used for its controllability, repeatability, and scalability. The Box-Behnken Design was employed to screen the formulations and flow parameters, while computational fluid dynamics was used to simulate the mixing process and predict the formation of liposomes. The optimized curcumin liposomes (Cur-LPs) had a size of 132.9 nm and an encapsulation efficiency of 97.1%, whereas the curcumin nanocrystals (Cur-NCs) had a size of 172.3 nm. Both Cur-LPs and Cur-NCs inhibited LPS-induced pro-inflammatory polarization of macrophages and reduced the expression and secretion of inflammatory factors. The mouse air pouch model further demonstrated that both dosage forms attenuated inflammatory cell infiltration and inflammatory fibrosis in subcutaneous tissues. Interestingly, the anti-inflammatory effect of Cur-LPs was more potent than that of Cur-NCs, both in vitro and in vivo, although the cellular uptake of Cur-NCs was quicker. In conclusion, the results demonstrate that Cur-LPs have great potential for the clinical treatment of inflammatory osteolysis and that the therapeutic effect is closely related to the liposomal dosage form.

Thiolutin attenuates ischemic stroke injury via inhibition of NLRP3 inflammasome: an in vitro and in vivo study.

A recent study confirmed that thiolutin is effective in the treatment of nucleotide-binding domain-like receptor protein 3 (NLRP3)-related inflammatory diseases. Nevertheless, whether thiolutin (THL) is involved in the regulation of NLRP3 inflammasome in ischemic stroke is not known. The murine neuronal cell oxygen-glucose deprivation (OGD) model was first established, and then different concentrations (25 nM and 50 nM) of THL were administered for 48 h incubation, respectively. Subsequently, cell viability and toxicity, and the levels of intracellular inflammatory factors interleukin-1ß (IL-1ß), interleukin-18 (IL-18), oxidative stress factors superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and malondialdehyde (MDA), and NLRP3 inflammasome activation-related proteins pro-caspase, caspase-1, apoptosis-associated speck like-protein (ASC) and NLRP3 were examined, respectively. We further established the mouse middle cerebral artery occlusion (MCAO) model to evaluate the therapeutic effects of THL on cerebral infarction like behaviors in mice and the preventive effects on NLRP3 inflammasome activation in vivo. Cell cytotoxic, and the levels of inflammatory factors and oxidative stress were conspicuously increased, and NLRP3 inflammasome was materially activated in the OGD-induced cell model and MCAO-established mouse model, which were partially countered by THL treatment. Besides, intraperitoneal injection of THL could prominently reduce the cerebral infarct volume and neuromotor deficit scores in MCAO mice. The present study confirmed that THL attenuated neuronal and cerebral inflammatory injury caused by OGD and MCAO models in mice through restraining NLRP3 inflammasome activation in vitro and in vivo.

Digital Pupillometry and Centroid Shift Changes in Dominant and Nondominant Eyes.

PURPOSE: To investigate the differences between dominant and nondominant eyes in a predominantly young patient population by analyzing the angle kappa, pupil size, and center position in dominant and nondominant eyes. METHODS: A total of 126 young college students (252 eyes) with myopia who underwent femtosecond laser-combined LASIK were randomly selected. Ocular dominance was determined using the hole-in-card test. The WaveLight Allegro Topolyzer (WaveLight Laser Technologies AG, Erlangen, Germany) was used to measure the pupil size and center position. The offset between the pupil center and the coaxially sighted corneal light reflex (P-Dist) of the patients was recorded by the x- and y-axis eyeball tracking adjustment program of the WaveLight Eagle Vision EX500 excimer laser system (Wavelight GmbH). The patient's vision (uncorrected distance visual acuity [UDVA], best-corrected visual acuity (BCVA), and refractive power (spherical equivalent, SE) were observed preoperatively, 1 week, 4 weeks, and 12 weeks postoperatively, and a quality of vision (QoV) questionnaire was completed. RESULTS: Ocular dominance occurred predominantly in the right eye [right vs. left: (178) 70.63% vs. (74) 29.37%; p < 0.001]. The P-Dist was 0.202 ± 0.095 mm in the dominant eye and 0.215 ± 0.103 mm in the nondominant eye (p = 0.021). The horizontal pupil shift was - 0.07 ± 0.14 mm in dominant eyes and 0.01 ± 0.13 mm in nondominant eyes (p = 0.001) (the temporal displacement of the dominant eye under mesopic conditions). The SE was negatively correlated with the P-Dist (r = - 0.223, p = 0.012 for the dominant eye and r = - 0.199, p = 0.025 for the nondominant eye). At 12 weeks postoperatively, the safety index (postoperative BDVA/preoperative BDVA) of the dominant and nondominant eyes was 1.20 (1.00, 1.22) and 1.20 (1.00, 1.20), respectively, and the efficacy index (postoperative UDVA/preoperative BDVA) was 1.00 (1.00, 1.20) and 1.00 (1.00, 1.20), respectively; the proportion of residual SE within ± 0.50 D was 98 and 100%, respectively. CONCLUSIONS: This study found that ocular dominance occurred predominantly in the right eye. The pupil size change was larger in the dominant eye. The angle kappa of the dominant eye was smaller than that of the nondominant eye and the pupil center of the dominant eye was slightly shifted to the temporal side under mesopic conditions. The correction of myopia in the dominant and nondominant eyes exhibits good safety, efficacy, and predictability in the short term after surgery, and has good subjective visual quality performance after correction. We suggest adjusting the angle kappa percentage in the dominant eye to be lower than that of the nondominant eye in individualized corneal refractive surgery in order to find the ablation center closest to the visual axis.

KPNA2 promotes angiogenesis by regulating STAT3 phosphorylation.

PURPOSE: Angiogenesis is involved in many pathological and physiological processes and is mainly driven by hypoxia. Karyopherin subunit alpha 2 (KPNA2), a member of the nuclear transport protein family, was recently shown to be induced by hypoxia in various types of tumours, so we aimed to investigate the role and mechanism of KPNA2 in angiogenesis under hypoxia. MATERIALS AND METHODS: After overexpression or knockdown of KPNA2 in human umbilical vein endothelial cells (HUVEC) by adenovirus vector infection, the tube formation, proliferation and migration of HUVEC under hypoxia were detected by tubule formation assay, 5-ethynyl-2'-deoxyuridine (EdU) staining and Transwell assay, respectively. After overexpression or knockdown of KPNA2 in a murine hindlimb ischemia model by local injection of purified adenovirus vector into the gastrocnemius muscle, blood flow changes were examined with a laser Doppler system. Changes in KPNA2-binding proteins under hypoxia were detected by immunoprecipitation-mass spectrometry (IP-MS) and co-immunoprecipitation (Co-IP). The effect of KPNA2 on signal transducer and activator of transcription 3 (STAT3) was detected by Western blotting and quantitative RT‒PCR. RESULTS: KPNA2 was upregulated in the HUVEC hypoxia model and murine hindlimb ischemia model. Overexpression of KPNA2 increased the proliferation, migration and tube formation of HUVEC under hypoxia, while knockdown of KPNA2 reduced the proliferation, migration and tube formation of HUVEC. Overexpression of KPNA2 promoted the restoration of blood flow in the murine hindlimb ischemia model, while knockout of KPNA2 inhibited the restoration of blood flow in the murine hindlimb ischemia model. Mechanistically, hypoxia promoted the binding of STAT3 to KPNA2. Overexpression of KPNA2 promoted STAT3 phosphorylation and then upregulated vascular endothelial growth factor (VEGF) and angiopoietin 2(ANGPT2), whereas knockdown of KPNA2 inhibited STAT3 phosphorylation and then downregulated VEGF and ANGPT2. CONCLUSION: Our study demonstrates that hypoxia promotes the binding of STAT3 to KPNA2 and KPNA2 promotes angiogenesis under hypoxia by promoting the binding of STAT3 and JAK1 and regulating STAT3 phosphorylation.

Quantitative Assessment of the Pupil: An Underrecognized Yet Important Factor Related to Orbital Blowout Fracture Repair.

PURPOSE: To investigate dynamic pupil changes after orbital blowout fracture repair. To compare postoperative changes in under photopic and mesopic pupil size and center position after orbital blowout fracture repair surgery. METHODS: The study evaluated 19 eyes. Pupils were imaged for pupil size and center position before and 3 months after orbital blowout fracture repair surgery. Pupil size changes were measured, and the correlation between preoperative and postoperative pupil centroid shift was evaluated. RESULTS: After repair, operative eyes exhibited a growth of 9.3% ±â€Š8.6% in pupil size, and contralateral eyes showed a growth of 8.6% ±â€Š8.2% (P = 0.011, P = 0.007). Similar findings were noted in mesopic conditions. Under mesopic conditions, the pupil of operative eyes in medial orbital wall fracture deviated 0.030 ±â€Š0.019 mm towards the nasal side along the X-axis (P = 0.031). The postoperative orbital floor fracture group demonstrated statistical significance at a spatial frequency of 5 (P = 0.041). CONCLUSIONS: Orbital blowout fracture repair surgery affects pupil size and center position.

MicroRNA-222-3p associated with Helicobacter pylori targets HIPK2 to promote cell proliferation, invasion, and inhibits apoptosis in gastric cancer.

Gastric cancer ranks as the second leading cause of malignancy-related death worldwide, and always diagnosed at advanced stage. MicroRNA-222-3p (miR-222-3p) is aberrantly upregulated in various malignant tumors including gastric cancer, but its role and underlying molecular mechanisms in gastric cancer remain largely unknown. Helicobacter pylori (H. pylori) infection acts as a trigger in the development of gastric cancer, and increasing evidence suggests that H. pylori affects microRNA expression. In this study, gastric cancer tissue samples were divided into H. pylori positive group (+) and negative group (-). QRT-PCR showed that miR-222-3p was significantly upregulated in H. pylori (+) group compared with H. pylori (-) group, and luciferase reporter assays identified homeodomain-interacting protein kinase 2 (HIPK2) as a novel target of miR-222-3p in gastric cancer. Immunohistochemistry revealed that HIPK2 levels were decreased in H. pylori (+) group compared with H. pylori (-). After that, functional experiments indicated that miR-222-3p overexpression promoted the proliferation and invasion, while inhibiting apoptosis of SGC7901 gastric cancer cells, but miR-222-3p knockdown exhibited the opposite effects. Also, HIPK2 knockdown induced similar effects as miR-222-3p overexpression in SGC7901 cells. Nude mouse experiments further suggested that HIPK2 overexpression signally attenuated the enhancing effect of miR-222-3p overexpression on cell proliferation, indicating that the effect of miR-222-3p on gastric cancer progression depends on HIPK2, at least in part. Overall, our results demonstrated that miR-222-3p/HIPK2 signal pathway regulated gastric cancer cell proliferation, apoptosis, and invasion, provided a novel therapeutic target for the treatment of gastric cancer infected by H. pylori.

Acupuncture for patients with mild to moderate Alzheimer's disease: a randomized controlled trial.

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia. However, none of medical treatment can stop or reverse the underlying neurodegenerative of AD at present. Acupuncture has attracted more and more attention in recent years due to its efficacy and very few side effects. Lately, a systematic review has thought that the evidence on the effectiveness of acupuncture in improving the cognitive function of AD patients was not powerful enough. Therefore, the aim of this study is to explore the efficacy and safety of acupuncture in patients with mild to moderate AD. METHODS: This was a randomized, controlled, parallel-group, exploratory study with 4-week baseline (T0), 12-week treatment phase (T1) and 12-week follow-up period (T2). Patients with mild to moderate AD meeting the included criteria were randomly allocated into either acupuncture or donepezil hydrochloride groups. The acupuncture group(AG) was given acupuncture treatment three times per week and the donepezil hydrochloride group(DG) group was administered donepezil hydrochloride once daily (5 mg/day for the first 4 weeks and 10 mg/day thereafter). Primary efficacy was measured using Alzheimer's disease Assessment Scale-Cognitive (ADAS-cog) and Clinician's Interview-Based Impression of Change-Plus (CIBIC-Plus). The second outcomes were measured with 23-Item Alzheimer's disease Cooperative Study Activities of Daily Living Scales (ADAS-ADL23) and Neuropsychiatric Index (NPI). RESULTS: Of 87 participants enrolled in the study, 79 patients finished their treatment and follow-up processes. The ADAS-cog scores for AG group showed obvious decreases at T2 and ∆(T2-T0)when compared with DG group, and significant between-group differences were detected (all p < 0.05). The mean CIBIC-Plus values for the AG group at T1 and T2 were much lower than that for the DG group, and there were significant differences between the two groups (푃<0.05). There were no significant between-group differences in the scores of ADAS-ADL23 and NPI during the study period. Treatment discontinuations due to adverse events were 0 (0%) and 4 (9.09%) for the AG and DG groups, respectively. CONCLUSIONS: Acupuncture is safe, well tolerated and effective in improving the cognitive function, global clinical status of AD. TRIAL REGISTRATION: ChiCTR-IOR-17010465 (Retroactively registered on 18 JAN 2017).

[Acupuncture Regulated the Expressions of Hsp84 and Hsp86 and Postponed Brain Aging in SAMP8].

Objective To observe the correlations between heat shock protein 84 ( Hsp84)/ Hsp86 and brain aging in senescence accelerated mouse prone 8 (SAMP8) and the regulation effects of acupuncture. Methods Ten senescence accelerated mouse resistant 1 (SAMR1) were recruited as a normal control group. Another 30 SAMP8 mice were divided into the blank control group, the acupuncture group, and the non-acupoint group by random digit table, 10 in each group. Mice in the acupuncture group received treatment with "Sanjiao" acupuncture method. Mice in the non-acupoint group were needled at two fixed non-acupoints located at bilateral hypochondrium of the body. Catching stimulus at equal volume was given to mice in the rest two groups. All intervention was performed once per day for 15 successive days. Neuromuscular coordination of mice was evaluated. Levels of oxidative stress and protein carbonyl were determined. mRNA and protein expression levels of Hsp84 and Hsp86 in the hippocampus of mice and Neuro-2a cells were detected using Real-time PCR and Western blot. Results Compared with the normal control group, the success rate of tight rope experiment was lowered (P <0. 01) , levels of super- oxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the hippocampus were reduced (P < 0. 01) , the levels of superoxide anion and protein carbonyl increased (P <0. 01, P <0. 05), mRNA and protein expression levels of Hsp84 and Hsp86 in the hippocampus decreased (P <0. 01) in the blank con- trol group. Compared with the blank control group and the non-acupoint group, the success rate of tight rope experiment was elevated (P <0. 05) , levels of SOD and GSH-Px were increased (P <0. 05, P < 0. 01) , the levels of superoxide anion and protein carbonyl decreased (P <0. 01 , P <0. 05), and expres- sion levels of Hsp84 and Hsp86 in the hippocampus increased (P <0. 01) in the acupuncture group. mR- NA expression levels of Hsp84 and Hsp86 were decreased in Neuro-2a cells after treated with AP21-35 (P <0. 01). Conclusions Increased oxidative damage of protein and decreased expression levels of Hsp84 and Hsp86 might be partial reasons for resulting in accumulation of denatured protein and brain aging in SAMP8. Acupuncture could delay brain aging by regulating the expressions of Hsp84 and Hsp86.

Cell-free circulating tumor DNA in plasma/serum of non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the common type of lung cancer, which is the leading cause of cancer death throughout the world. Most patients were diagnosed too late for curative treatment. So, it is necessary to develop a minimal invasive method to identify NSCLC at an early stage. In recent years, cell-free circulating tumor DNA (ctDNA) has attracted increasing attention as a potential tumor marker for its minimal invasive, convenient, and easily accepted properties. The amount of ctDNA in plasma or serum was significantly higher in NSCLC patients than that in healthy controls or patients with benign diseases. Furthermore, many studies have proved an association among tumor stage, tumor grade, lymph node involvement, the number of metastatic sites, tumor response, survival outcome, and the ctDNA levels. Many genetic changes, such as gene mutation, loss of heterozygosity, microsatellite instability, and gene methylation were also found in ctDNA in NSCLC patients. These findings demonstrated that the ctDNA could serve as a viable tool to monitor NSCLC and prompted us to find more sensitive and specific biomarkers for clinical practice, especially monitor these cases with at least one known gene abnormality. Here, we reviewed the evidence of ctDNA in NSCLC and consider possible future applications in patient management.

[Effect of acupuncture on transmembrane signal pathway in AD mice: an analysis based on lipid-raft proteomics].

OBJECTIVE: To reveal the transmembrane signal pathway participating in regulating neuron functions of treating Alzheimer's disease (AD) by acupuncture. METHODS: SAMP8 mice was used for AD animal model. The effect of acupuncture method for qi benefiting, blood regulating, health supporting, and root strengthening on the amount and varieties of transmembrane signal proteins from hippocampal lipid rafts in SAMP8 mice was detected using HPLC MS/MS proteomics method. RESULTS: Compared with the control group, acupuncture increased 39 transmembrane signal proteins from hippocampal lipid rafts in SAMP8 mice, of them, 14 belonged to ionophorous protein, 8 to G protein, 8 to transmembrane signal receptor, and 9 to kinase protein. Totally 3 main cell signal pathways were involved, including G-protein-coupled receptors signal, enzyme linked receptor signal, and ion-channel mediated signal. Compared with the sham-acupuncture group, acupuncture resulted in significant increase of kinase signal protein amount. From the aspect of functions, they were dominant in regulating synapse functions relevant to cytoskeleton and secreting neurotransmitters. CONCLUSION: The cell biological mechanism for treating AD by acupuncture might be achieved by improving synapse functions and promoting the secretion of neurotransmitters through transmembrane signal transduction, thus improving cognitive function of AD patients.

A fluorine-based strong and healable elastomer with unprecedented puncture resistance for high performance flexible electronics.

There is usually a trade-off between high mechanical strength and dynamic self-healing because the mechanisms of these properties are mutually exclusive. Herein, we design and fabricate a fluorinated phenolic polyurethane (FPPU) elastomer based on octafluoro-4,4'-biphenol to overcome this challenge. This fluorine-based motif not only tunes interchain interactions through π-π stacking between aromatic rings and free-volume among polymer chains but also improves the reversibility of phenol-carbamate bonds via electron-withdrawing effect of fluorine atoms. The developed FPPU elastomer shows the highest recorded puncture energy (648.0 mJ), high tensile strength (27.0 MPa), as well as excellent self-healing efficiency (92.3%), along with low surface energy (50.9 MJ m-2), notch-insensitivity, and reprocessability compared with non-fluorinated counterpart biphenolic polyurethane (BPPU) elastomer. Taking advantage of the above-mentioned merits of FPPU elastomer, we prepare an anti-fouling triboelectric nanogenerator (TENG) with a self-healable, and reprocessable elastic substrate. Benefiting from stronger electron affinity of fluorine atoms than hydrogen atoms, this electronic device exhibits ultrahigh peak open-circuit voltage of 302.3 V compared to the TENG fabricated from BPPU elastomer. Furthermore, a healable and stretchable conductive composite is prepared. This research provides a distinct and general pathway toward constructing high-performance elastomers and will enable a series of new applications.

Accumulation of the bitter substance quercetin mediated by the overexpression of a novel seed-specific gene FtRDE2 in Tartary buckwheat.

Tartary buckwheat (Fagopyrum tataricum) is frequently employed as a resource to develop health foods, owing to its abundant flavonoids such as rutin. However, the consumption of Tartary buckwheat (TB) is limited in food products due to the strong bitterness induced by the hydrolysis of rutin into quercetin. This transformation is facilitated by the degrading enzyme (RDE). While multiple RDE isoenzymes exist in TB, the superior coding gene of FtRDEs has not been fully explored, which hinders the breeding of TB varieties with minimal bitterness. Here, we found that FtRDE2 is the most abundant enzyme in RDE crude extracts, and its corresponding gene is specifically expressed in TB seeds. Results showed that FtRDE2 has strong rutin hydrolysis activity. Overexpression of FtRDE2 not only significantly promoted rutin hydrolysis and quercetin accumulation but also dramatically upregulated genes involved in the early phase of flavonoid synthesis (FtPAL1、FtC4H1、Ft4CL1, FtCHI1) and anthocyanin metabolism (FtDFR1). These findings elucidate the role of FtRDE2, emphasizing it as an endogenous factor contributing to the bitterness in TB and its involvement in the metabolic regulatory network. Moreover, correlation analysis revealed a positive relationship between the catalytic activity of RDE extracts and the expression level of FtRDE2 during seed germination. In summary, our results suggest that FtRDE2 can serve as a promising candidate for the molecular breeding of a TB variety with minimal bitterness.

Typical emerging contaminants in sewage treatment plant effluent, and related watersheds in the Pearl River Basin: Ecological risks and source identification.

Emerging contaminants pose a potential risk to aquatic ecosystems in the Pearl River Basin, China, owing to the high population density and active industry. This study investigated samples from eight sewage treatment plants, and five surface water bodies of related watersheds. To screen the risk of emerging contaminants (ECs), and clarify their sources, this study calculated the risk quotient of detected chemical and performed source identification/apportionment using the positive matrix factorization method. In total, 149 organic pollutants were identified. Pharmaceuticals showed significant concentrations in sewage treatment plant samples (120.87 ng/L), compared with surface water samples (1.13 ng/L). The ecological risk assessment identified three chemicals with a heightened risk to aquatic organisms: fipronil sulfide, caffeine, and roxithromycin. Four principal sources of contaminants were identified: pharmaceutical wastewater, domestic sewage, medical effluent, and agricultural runoff. Pharmaceutical wastewater was the primary contributor (60.4 %), to the cumulative EC concentration and to ECs in sewage treatment plant effluent. Agricultural drainage was the main source of ECs in surface water. This study provides a strategy to obtain comprehensive information on the aquatic risks and potential sources of EC species in areas affected by artificial activities, which is of substantial importance to pollutant management and control.

Age-related alteration in cerebral blood flow and energy failure is correlated with cognitive impairment in the senescence-accelerated prone mouse strain 8 (SAMP8).

Cerebrovascular dysfunction is an early pathogenic event in Alzheimer's disease (AD) and plays a key role in the disease process. Cerebral hypoperfusion, brain glucose hypometabolism and disrupted blood-brain barrier (BBB) integrity contributed to the onset and progression of AD. However, the relationships between the age-related cognitive impairment and cerebral blood flow (CBF), energy metabolism and BBB have not been clearly explained. In this study, we investigated the cognitive function, CBF, BBB damage and expression level of glucose transporter (GLUT) 1 and 3 of senescence-accelerated mouse prone 8 (SAMP8), and the correlations between each of them were analyzed. When compared with SAMR1 (senescence-accelerated mouse resistant 1), the cognitive abilities of SAMP8 were damaged apparently even at 4 months of age, showing up a slower and more capricious acquisition in Morris water maze tasks. In both SAMP8 and SAMR1, reduced CBF and increased BBB leakage were observed with increasing age, but an earlier and more severe impairment was detected in SAMP8. In addition, alterations of GLUT1 and GLUT3 protein expression in cortex and hippocampus were more prominent in SAMP8. Correlation analysis demonstrated that the increased escape latency was correlated negatively with CBF and expression of glucose transporters; and positively with BBB permeability in the hippocampus. These results suggested that CBF, BBB integrity, the expression of GLUT1 and GLUT3 were significantly affected by age and strain, which were also closely associated with cognitive ability. The alteration in CBF and energy failure induced by aging and vascular insults resulted in cognitive decline in SAMP8.

Mechanisms of Hydride Nucleation, Growth, Reorientation, and Embrittlement in Zirconium: A Review.

Zirconium (Zr) hydrides threaten the reliability of fuel assembly and have repeatedly induced failures in cladding tubes and pressure vessels. Thus, they attract a broad range of research interests. For example, delayed hydride cracking induced a severe fracture and failure in a Zircaloy-2 pressure tube in 1983, causing the emergency shutdown of the Pickering nuclear reactor. Hydride has high hardness and very low toughness, and it tends to aggregate toward cooler or tensile regions, which initiates localized hydride precipitation and results in delayed hydride cracking. Notably, hydride reorientation under tensile stress substantially decreases the fracture toughness and increases the ductile-to-brittle transition temperature of Zr alloys, which reduces the safety of the long-term storage of spent nuclear fuel. Therefore, improving our knowledge of Zr hydrides is useful for effectively controlling hydride embrittlement in fuel assembly. The aim of this review is to reorganize the mechanisms of hydride nucleation and growth behaviors, hydride reorientation under external stress, and hydride-induced embrittlement. We revisit important examples of progress of research in this field and emphasize the key future aspects of research on Zr hydrides.

Neural correlates of intelligence: ERP Components of temporary storage predict fluid intelligence over and above those of executive functions.

Previous research has revealed that individuals with different levels of intelligence exhibit distinct patterns of event-related potentials (ERPs) related to executive functions and temporary storage. However, there is a lack of studies investigating the relative contributions of these ERPs in predicting individual differences in fluid intelligence. This study aims to examine the extent to which ERPs associated with executive functions and temporary storage can predict individual differences in fluid intelligence. Special attention is given to determining whether electrophysiological activities of temporary storage can predict fluid intelligence after accounting for executive functions, and vice versa. Both executive attention and temporary storage were measured by two experimental tasks, while electroencephalographic data were collected simultaneously. Fluid intelligence was assessed by two established tests. To address previous inconsistencies due to small sample sizes, a relatively large sample of young adults (N = 136) was recruited. The results revealed that participants with lower fluid intelligence displayed larger P3 amplitudes in the executive functions and temporary storage tasks compared to those with higher fluid intelligence. Additionally, the amplitudes of frontal and parietal P3s elicited by both executive functions and temporary storage significantly predicted fluid intelligence. Interestingly, the frontal and parietal P3s associated with temporary storage predicted fluid intelligence beyond the contributions of executive functions, supporting the storage account of individual differences in fluid intelligence. This study provides an original and fresh understanding of how executive functions and temporary storage contribute to fluid intelligence, offering new insights into the neurocognitive mechanisms underlying intelligence.

A systematic review and meta-analysis of nursing effect of fast-track recovery surgery on patients undergoing total endoscopic resection of esophageal cancer: fast-track recovery surgery vs. nursing care as usual.

Background: Esophageal cancer (EC) is the 6th leading cause of cancer-related deaths worldwide, and the morbidity and mortality of EC have continued to increase in recent years. The results of the clinical application of the Fast-track recovery surgery (FTS) concept in nursing interventions for EC patients after total endoscopic esophagectomy are unconvincing. This study sought to evaluate the nursing effect of the fast-track recovery surgical nursing model on patients with EC after total cavity endoscopic esophagectomy. Methods: We searched for articles on case-control trials about nursing interventions after total endoscopic esophagectomy. The search time was set from January 2010 to May 2022. The data were independently extracted by 2 researchers. RevMan5.3 statistical software (Cochrane) was used to analyze the extracted data. All the articles included in the review were assessed for risk of bias using the Cochrane Handbook 5.3 (https://training.cochrane.org/). Results: Ultimately, 8 clinical controlled trials, comprising 613 cases, were identified. A meta-analysis was conducted of the extubation times, and the results showed that the study group's extubation times were remarkably shorter. In relation to the exhaust times, the study group had significantly shorter exhaust times than control group (P<0.05). In relation to the time, it took patients to leave bed, patients in the study group left bed in a considerably shorter time compared with controls (P<0.00001). In relation to the hospitalization time, a remarkable reduction in the length of hospital stay was observed in the study group (P<0.00001). The analysis of the funnel plots showed a small number of asymmetries, suggesting that the number of articles included was small due to the heterogeneity of the studies (P<0.00001). Conclusions: FTS care is effective at accelerating patients' postoperative recovery. This model of care needs to be further validated in the future by higher-quality and longer follow-up studies.

Prediction of early neurological deterioration in acute ischemic stroke patients treated with intravenous thrombolysis.

A proportion of acute ischemic stroke (AIS) patients suffer from early neurological deterioration (END) within 24 hours following intravenous thrombolysis (IVT), which greatly increases the risk of poor prognosis of these patients. Therefore, we aimed to explore the predictors of early neurological deterioration of ischemic origin (ENDi) in AIS patients after IVT and develop a nomogram prediction model. This study collected 244 AIS patients with post-thrombolysis ENDi as the derivation cohort and 155 patients as the validation cohort. To establish a nomogram prediction model, risk factors were identified by multivariate logistic regression analysis. The results showed that neutrophil to lymphocyte ratio (NLR) (OR 2.616, 95% CI 1.640-4.175, P < 0.001), mean platelet volume (MPV) (OR 3.334, 95% CI 1.351-8.299, P = 0.009), body mass index (BMI) (OR 1.979, 95% CI 1.285-3.048, P = 0.002) and atrial fibrillation (AF) (OR 8.012, 95% CI 1.341-47.873, P = 0.023) were significantly associated with ENDi. The area under the curve of the prediction model constructed from the above four factors was 0.981 (95% CI 0.961-1.000) and the calibration curve was close to the ideal diagonal line. Therefore, this nomogram prediction model exhibited good discrimination and calibration power and might be a reliable and easy-to-use tool to predict post-thrombolysis ENDi in AIS patients.

AIM2 promotes renal cell carcinoma progression and sunitinib resistance through FOXO3a-ACSL4 axis-regulated ferroptosis.

Renal cell carcinoma (RCC) is a serious threat to people's health due to its rapid progression, and patients easily develop resistance to targeted therapy. The absent in melanoma 2 (AIM2) is a receptor protein that has recently been proposed to play an important role in various diseases. In this study, AIM2 was identified as a new biomarker of RCC and promoted RCC progression and sunitinib resistance in an inflammasome-independent manner. Mechanistically, AIM2 promoted FOXO3a phosphorylation and proteasome degradation, thereby reducing its transcriptional effect on ACSL4 and inhibiting ferroptosis. In summary, AIM2 promoted RCC progression and sunitinib resistance through FOXO3a-ACSL4 axis-regulated ferroptosis, which could provide new ideas and therapeutic targets for RCC diagnosis and treatment.