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A bidirectional relationship between cognitive reserve and cognition among older adults in a rural Chinese community: a cross-lagged design

BackgroundThe concept of cognitive reserve (CR) plays a crucial role in understanding cognitive aging and resilience. Accumulating evidence revealed the influence of CR proxy on cognitive function, but it remains unknown whether a reverse association or reciprocal effect exists.ObjectiveThe aim of this study is to observe the bidirectional relationship between cognitive reserve proxies and cognitive function among older adults in rural Chinese communities, providing a better understanding of the underlying mechanisms and potential moderating factors involved.MethodThis longitudinal study analyzed 792 older adults (70.23 ± 5.87 years; 59.8%female) aged 60 years and older from the health status of rural older adults (HSRO) study over a 3-year period. Cognition was assessed by the Mini-Mental State Examination (MMSE). Cross-lagged panel modeling was utilized to analyze the interrelationship between cognitive reserve proxies and cognitive performance. Additionally, latent profile analysis was employed to identify different subtypes of neuropathic load within the study population.ResultsOur cross-lagged analyses revealed significant associations between CR at T0 and MMSE scores at T1 (β = 0.81), as well as between MMSE scores at T0 and CR at T1 (β = 0.04). However, when conducting stratified analyses, we found no significant lagged relationships among individuals with high neuropathic load or those at an advanced age (p > 0.05). Furthermore, our longitudinal comparisons indicated changes in the contribution of CR proxy factors over time.ConclusionThe findings suggested a bidirectional relationship between cognitive reserve and cognitive performance in older adults. These results emphasized the importance of implementing timely public health measures to enhance cognitive reserve and cognitive performance ultimately promoting healthier aging among older adults

Network Reconnaissance and Vulnerability Excavation of Secure DDS Systems

Data Distribution Service (DDS) is a realtime peer- to-peer protocol that serves as a scalable middleware between distributed networked systems found in many Industrial IoT domains such as automotive, medical, energy, and defense. Since the initial ratification of the standard, specifications have introduced a Security Model and Service Plugin Interface (SPI) architecture, facilitating authenticated encryption and data centric access control while preserving interoperable data exchange. However, as Secure DDS v1.1, the default plugin specifications presently exchanges digitally signed capability lists of both participants in the clear during the crypto handshake for permission attestation; this breaches confidentiality of the context of the connection. In this work, we present an attacker model that makes use of network reconnaissance afforded by this leaked context in conjunction with formal verification and model checking to arbitrarily reason about the underlying topology and reachability of information flow, enabling targeted attacks such as selective denial of service, adversarial partitioning of the data bus, or vulnerability excavation of vendor implementations

Design, synthesis and biological evaluation of a novel colchicine-magnolol hybrid for inhibiting the growth of Lewis lung carcinoma in Vitro and in Vivo

Colchicine is a bioactive alkaloid originally from Colchicum autumnale and possesses excellent antiproliferative activity. However, colchicine-associated severe toxicity, gastrointestinal side effects in particular, limits its further therapeutic use. In the current study, we thus designed and synthesized a novel hybrid (CMH) by splicing colchicine and magnolol, a multifunctional polyphenol showing favorable gastrointestinal protection. The antitumor activity of CMH in Lewis lung carcinoma (LLC) was then evaluated in vitro and in vivo. Biologically, CMH inhibited the growth of LLC cells with an IC50 of 0.26 μM, 100 times more potently than cisplatin (26.05 μM) did. Meanwhile, the cytotoxicity of CMH was 10-fold lower than that of colchicine in normal human lung cells (BEAS-2B). In C57BL/6 mice xenograft model, CMH (0.5 mg/kg) worked as efficacious as colchicine (0.5 mg/kg) to inhibit tumor growth and 2 times more potently than cisplatin (1 mg/kg). In terms of mortality, 7 out of 10 mice died in colchicine group (0.75 mg/kg), while no death was observed in groups receiving CMH or cisplatin at 0.75 mg/kg. Mechanistic studies using Western blot revealed that CMH dose-dependently suppressed the protein expression of phosphorylated ERK. Molecular docking analysis further indicated that CMH was well fitted in the colchicine binding site of tubulin and formed several hydrogen bonds with tubulin protein. These results enable our novel hybrid CMH as a potential antineoplastic agent with lower toxicity, and provide perquisites for further investigation to confirm the therapeutic potentiality of this novel hybrid

Co-delivery of resveratrol and docetaxel via polymeric micelles to improve the treatment of drug-resistant tumors

Co-delivery of anti-cancer drugs is promising to improve the efficacy of cancer treatment. This study was aiming to investigate the potential of concurrent delivery of resveratrol (RES) and docetaxel (DTX) via polymeric nanocarriers to treat breast cancer. To this end, methoxyl poly(ethylene glycol)-poly(d,l-lactide) copolymer (mPEG-PDLA) was prepared and characterized using FTIR and 1H NMR, and their molecular weights were determined by GPC. Isobologram analysis and combination index calculation were performed to find the optimal ratio between RES and DTX to against human breast adenocarcinoma cell line (MCF-7 cells). Subsequently, RES and DTX were loaded in the mPEG-PDLA micelles simultaneously, and the morphology, particle size distribution, in vitro release, pharmacokinetic profiles, as well as cytotoxicity to the MCF-7 cells were characterized. IC50 of RES and DTX in MCF-7 cells were determined to be 23.0 µg/ml and 10.4 µg/ml, respectively, while a lower IC50 of 4.8 µg/ml of the combination of RES and DTX was obtained. The combination of RES and DTX at a ratio of 1:1 (w/w) generated stronger synergistic effect than other ratios in the MCF-7 cells. RES and DTX loaded mPEG-PDLA micelles exhibited prolonged release profiles, and enhanced cytotoxicity in vitro against MCF-7 cells. The AUC(0→t) of DTX and RES in mPEG-PDLA micelles after i.v. administration to rats were 3.0-fold and 1.6-fold higher than that of i.v. injections of the individual drugs. These findings indicated that the co-delivery of RES and DTX using mPEG-PDLA micelles could have better treatment of tumors. Keywords: Resveratrol, Docetaxel, Methoxyl poly(ethylene glycol)-poly(d,l-lactide) copolymer (mPEG-PDLA), Micelles, Drug resistance tumo

The efficacy and safety of Niaoduqing granules in the treatment of diabetic kidney disease: a systematic review and meta-analysis

Background: Diabetic nephropathy (DN) is the main cause of chronic kidney disease (CKD) and end-stage renal failure (ESRF), and the control of disease progression and adverse events during treatment needs to be improved.Objective: This study aimed to systematically evaluate the clinical efficacy and safety of Niaoduqing granules (NDQG) in the treatment of diabetic kidney disease (DKD).Method: Randomized controlled trials (RCTs) of NDQG for DKD from Chinese and English databases up to 31 August 2022 were included. The quality of the literature was assessed using the risk of bias tool of the Cochrane Handbook. At a 95% confidence interval (CI), relative risk (RR) and Cohen’s d were used for the categorical and continuous variables, respectively, and Stata 16.0 software was used for statistical analysis. A funnel plot and Egger’s tests were used to assess publication bias.Result: A total of 4,006 patients were included in 52 RCTs, including 1,987 cases in the control group and 2,019 cases in the treatment group. Compared with conventional treatment (CT), combined NDQG therapy is more effective in improving clinical efficiency [RR = 1.23, 95% confidence interval (1.17, 1.29), p < 0.001, I2 = 53.17%], kidney function (urinary albumin excretion rate [SMD = −0.90, 95% CI (−1.14, −0.66), p < 0.001, I2 = 78.19%], 24hUTP levels [SMD = −0.81, 95% CI (−1.08, −0.55), p < 0.001, I2 = 87.08%], blood urea nitrogen [SMD = −0.54, 95% CI (−0.69, −0.39), p < 0.01, I2 = 77.01%], SCr [SMD = −0.68, 95% CI (−0.90, −0.45), p < 0.001, I2 = 89.97%], CCr [SMD = 0.76, 95% CI (0.10,1.42), p = 0.02, I2 = 95.97%], and Cys-C [SMD = −1.32, 95% CI (−2.25, −0.40), p = 0.01, I2 = 93.44%]), the level of glucose metabolism (fasting blood glucose [SMD = −0.18, 95% CI (−0.38, 0.03), p = 0.10, I2 = 71.18%] and HbA1c [SMD = −0.42, 95% CI (−0.86, −0.02), p = 0.06, I2 = 81.64%]), the level of lipid metabolism (total cholesterol [SMD = −0.70, 95% CI (−1.01, −0.39), p < 0.001, I2 = 86.74%] and triglyceride [SMD = −0.61, 95% CI (−0.87,−0.36), p < 0.001, I2 = 80.64%]), inflammatory factors (Hs-CRP [SMD = −1.00, 95% CI (−1.54, −0.46), p < 0.001, I2 = 86.81%], IL-18 [SMD = −1.25, 95% CI (−1.58, −0.92), p < 0.001, I2 = 0], and TNF-α [SMD = −1.28, 95% CI (−1.64, −0.91), p < 0.001, I2 = 75.73%]), and indicators of oxidative stress (malondialdehyde [SMD = −0.88, 95% CI (−1.22, −0.54), p < 0.001, I2 = 66.01%] and advanced oxidation protein products [SMD = −0.92, 95% CI (−1.85, 0.00), p < 0.001, I2 = 90.68%]). In terms of improving uric acid [SMD = −1.59, 95% CI (−3.45, 0.27), p = 0.09, I2 = 94.67%], 2hPG [SMD = −0.04, 95% CI (−0.61, 0.53), p = 0.89, I2 = 84.33%], HDL-C [SMD = 0.71, 95% CI (0.02, 1.40), p = 0.04, I2 = 87.43%], Hb [SMD = 0.11, 95% CI (−0.10, 0.32), p = 0.32, I2 = 0.00]), and superoxide dismutase [SMD = 1.32, 95% CI (0.44, 2.20), p < 0.001, I2 = 93.48%], the effect is not obvious. Adjuvant treatment with NDQG did not increase the incidence of adverse reactions in the control group [SMD = 0.98, 95% CI (0.71, 1.34), p = 0.89, I2 = 1.59%]. Obvious publication bias was detected by funnel plot and Egger’s test.Conclusion: Our meta-analysis showed that adjuvant treatment with NDQG has more advantages than conventional treatment alone in the DKD treatment, which could improve clinical efficiency, kidney function, the level of glucose metabolism, the level of lipid metabolism, inflammatory factors, and oxidative stress indicators. At the same time, it also showed that NDQG are relatively safe. However, more high-quality studies are needed to provide more reliable evidence for clinical use.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022373726, identifier CRD42022373726

Fusobacterium nucleatum induces colon anastomosis leak by activating epithelial cells to express MMP9

BackgroundDespite advances in anastomotic techniques and perioperative care, the incidence of anastomotic leak (AL) has not substantially decreased over time. Although it is known that AL etiology is multifactorial and the mechanisms involved remain unclear, there is accumulating evidence pointing at AL related to gut microbiota.MethodWe firstly performed a clinical study to analyze the gut microbiota between colorectal cancer patients who developed AL and those who did not (nAL) using 16S-rRNA sequencing and quantitative real-time PCR to identify AL risk bacterial taxa. Then we built a rat anastomosis model and performed a bacteria transplantation to ensure the cause-effect relationship. The anastomotic healing score was used to evaluate the healing of anastomosis. In addition, we assessed the adhesion ability of bacteria by staining with fluorescein isothiocyanate and attachment assay. The expression of matrix metalloproteinase 9 (MMP9) was detected by western blot, and the activity was detected by gelatin zymography.ResultsWe found that the abundance and positive rate of Fusobacterium nucleatum (Fn) were higher in the AL patients. Exposure of the rat’s colon anastomosis to Fn contributes to the loss of submucosa collagen I and III, leading to AL’s pathogenesis. Fn can attach to the gut epithelial cells and stimulate intestinal MMP9 expression in vitro and in vivo. We further confirmed that these effects of Fn depended on the E-cadherin/β-catenin signaling pathway.ConclusionThis work demonstrates that Fn attaches and then stimulates the expression of epithelial cells MMP9 by the E-cadherin/β-catenin signaling pathway. These effects contribute to collagen break down in the intestinal tissue, finally leading to AL

Do leaders matter? : Chinese politics, leadership transition and the 17th Party Congress

The opaque nature of decision making in China has generated considerable interest in the internecine machinations of elite politics. Particularly, but not only, when it comes to issues of leadership transition, considerations of factional formation and conflict come to the fore. This is partly to explain the transition process itself, but also out of concern for how new leaders might change the direction of Chinese policy. This paper suggests that whilst leaders and leadership changes do matter, they matter less than they once did. This is partly a result of the de-ideologicization and increasing diverse nature of elite interests and group formation. But it is also partly a result of the changed nature of China’s political economy; in short, there is less desire and less ability for new leaders to impose a clear paradigm shift

Effects of Dietary Sodium and Chloride on Slaughter Performance, Digestive Tract Development and Tibia Mineralization of Geese

This study evaluated the slaughter performance, digestive tract development and tibia mineralization effects of sodium (Na) and chloride (Cl) on geese. Four hundred and thirty-four male geese at 29 days were randomly assigned into nine groups with six replicates (eight in each). The experiment employed a 3 × 3 factorial design, with two instances each of three Na levels (0.10%, 0.15%, and 0.20%) and three Cl levels (0.15%, 0.20%, and 0.25%). All experimental birds were husbanded for 42 days. Dietary Na and Cl levels and their interactions (Na ×Cl) had no significant effect on the slaughter, breast, thigh, abdominal fat yield, and digestive tract index of geese (p > 0.05). However, dietary Na and Cl level significantly affected the crypt depth of the jejunum and tibial development. Variations in Na and Cl levels had a significant interaction on the crypt depth of jejunal (p p p > 0.05), but its interaction significantly affected the calcium (Ca) content of bone (p < 0.05). When the Na and Cl levels were 0.15% and 0.15%, respectively, the Ca content in bone was the highest. These results suggest that dietary Na and Cl had interactive effects on geese, especially in the development of the tibia. High dietary Na and Cl levels adversely influenced the tibia and intestinal crypt morphology. Therefore, we do not advocate supplementing too much Na or Cl in the diet. Combined with our previous results, for 29–70-day-old geese, it is recommended that dietary Na and Cl levels should be 0.10% and 0.15%, respectively

Effect of Heating Time of Cottonseed Meal on Nutrient and Mineral Element Digestibility in Chicken (Based on Cottonseed Meal Replaced with All Soybean Meal)

A digestibility test was conducted to estimate the effects of the heating time of cottonseed meal on nutrient digestibility and mineral element absorption in chicken. A total of 36, 45-week-old healthy New Yangzhou chickens with similar body weight were randomly divided into 6 groups with 6 replicates per group and one chicken per replicate. The chickens in Group A (control group) were fed the corn-soybean meal diet. The chickens in Groups B, C, D, E, and F (experimental groups) were fed the cottonseed meal to replace all soybean meal. The cottonseed meal in the experimental groups was treated with wet heating. The heating temperature was set at 120 °C, and the humidity was set at 50%. The heating time was set to 10, 15, 20, 25, and 30 min successively. The trial period was 4 day. The digestibility of crude protein, metabolic energy, and dry matter was highest using wet-heat treating for 15 min (p 0.05). The digestibility of Fe increased significantly from 66.78% to 70.39% when the heating time of cottonseed meal was prolonged from 10 min to 30 min (p 0.05). Compared with Group A, the digestibility of Zn was increased in Groups B and C, and then there was a decrease in Group D. Finally, the digestibility was increased again in Group F. The opposite pattern was shown in the digestibility of Cu and Zn. There was no significant effect of wet heat treatment time on the digestibility of calcium, phosphorus, and manganese (p > 0.05). When cottonseed meal is considered as feed for 45-week-old chickens, processing conditions of 120 °C and 50% humidity for 15 min are recommended