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Background: The current lack of effective drug therapies for Alzheimer’s disease (AD) has prompted researchers to seek alternative nutritional therapies, such as medium chain triglycerides (MCTs). However, results are inconclusive. Objective: This systematic review and meta-analysis aims to summarize current evidence on the effect of MCT on cognitive function in patients with mild cognitive impairment (MCI) or AD. Methods: A systematic search was conducted up until December 16, 2022, to identify human interventions reporting the effects of MCT on cognitive functioning of MCI or AD patients. 995 non-duplicated publications were identified, of which nine (n = 10 studies) met the inclusion criteria. Results: Meta-analysis showed cognitive improvements in general (SMD = 0.64; 95% CI [0.05, 1.24]), but not in memory, language, and attention domains after oral MCT administration, compared to placebo. The effect of MCT was greater among APOE ɛ4 (−) subjects than APOE ɛ4 (+) subjects (SMD = 1.87; 95% CI [0.35, 3.40]). Conclusion: This review provides some evidence that treatment with MCT could improve general cognitive function in APOE ɛ4 (−) cognitive impaired patients. Better characterized clinical studies are warranted before making a definitive conclusion on the use of MCT for MCI and AD management.

PURPOSE We conducted a phase II trial evaluating the efficacy of VEGFR inhibitor axitinib and PD-L1 inhibitor avelumab in patients with recurrent/metastatic adenoid cystic carcinoma (R/M ACC). PATIENTS AND METHODS Eligible patients had R/M ACC with progression within 6 months before enrollment. Treatment consisted of axitinib and avelumab. The primary end point was objective response rate (ORR) per RECIST 1.1; secondary end points included progression-free survival (PFS), overall survival (OS), and toxicity. Simon's optimal two-stage design tested the null hypothesis of ORR ≤5% versus ORR ≥20% at 6 months; ≥4 responses in 29 patients would reject the null hypothesis. RESULTS Forty patients enrolled from July 2019 to June 2021; 28 were evaluable for efficacy (six screen failures; six evaluable for safety only). The confirmed ORR was 18% (95% CI, 6.1 to 36.9); there was one unconfirmed partial response (PR). Two patients achieved PR after 6 months; thus, the ORR at 6 months was 14%. The median follow-up time for surviving patients was 22 months (95% CI, 16.6 to 39.1 months). The median PFS was 7.3 months (95% CI, 3.7 to 11.2 months), 6-month PFS rate was 57% (95% CI, 41 to 78), and median OS was 16.6 months (95% CI, 12.4 to not reached months). Most common treatment-related adverse events (TRAEs) included fatigue (62%), hypertension (32%), and diarrhea (32%). Ten (29%) patients had serious TRAEs, all grade 3; four patients (12%) discontinued avelumab, and nine patients (26%) underwent axitinib dose reduction. CONCLUSION The study reached its primary end point with ≥4 PRs in 28 evaluable patients (confirmed ORR of 18%). The potential added benefit of avelumab to axitinib in ACC requires further investigation.

As the information technology develops, network attacks have become complex and diverse. To improve the effectiveness and accuracy of data security defense strategies, an optimal defense method based on improving evolutionary game model between heterogeneous groups is proposed. Specifically, based on traditional evolutionary game theory, the player type space is added to divide the heterogeneous groups, and the group type and game strategy are extended to N to solve the problems in heterogeneous groups. Considering the game is interfered by the environment, a set of dynamic environment functions is added to increase the adaptability of the model when dealing with changing complex networks. Taking into account the influence of information communication within the group, the information flow degree is added to increase the accuracy of evolution rate and solve the problem that traditional model cannot reveal the difference in the evolution rate of players. Based on the new model, taking the game between two types of invaders and one type of defender as an example, the calculation method of evolution direction at any time and the judgment method for the stability of equilibrium point are discussed. Finally, the effectiveness of the improved model is verified through the comparison of simulation experiments, and a new scheme is provided for current network data protection. &nbsp

Background: Vascular endothelium and smooth muscle work together to keep the balance of vasomotor tone and jointly maintain vascular homeostasis. Ca 2+ -permeable ion channel TRPV4 (transient receptor potential vanilloid family member 4) in endothelial cells regulates endothelium-dependent vasodilation and contraction in various states. However, how vascular smooth muscle cell TRPV4 (TRPV4 SMC ) contributes to vascular function and blood pressure regulation in physiological and pathologically obese condition has not been fully studied. Methods: We generated smooth muscle TRPV4-deficient mice and developed diet-induced obese mice model and analyzed the role of TRPV4 SMC in intracellular Ca 2+ ([Ca 2+ ] i ) regulation and vasoconstriction. Vasomotor changes of mouse mesenteric artery were measured by wire, and pressure myography. [Ca 2+ ] i were measured by fluo-4 staining. Blood pressure was recorded by telemetric device. Results: Vascular TRPV4 SMC played different roles in regulating vasomotor tone than endothelial TRPV4 due to their different features of [Ca 2+ ] i regulation. Loss of TRPV4 SMC attenuated U46619- and phenylephrine-induced contraction, suggesting its involvement in regulating vascular contractility. Mesenteric arteries from obese mice showed SMC hyperplasia, suggesting an increased level of TRPV4 SMC . Loss of TRPV4 SMC did not influence the development of obesity but protected mice from obesity-induced vasoconstriction and hypertension. In arteries deficient in SMC TRPV4, SMCs F-actin polymerization and RhoA dephosphorylation were attenuated under contractile stimuli. Moreover, SMC-dependent vasoconstriction was inhibited in human resistance arteries with TRPV4 inhibitor application. Conclusions: Our data identify TRPV4 SMC as a regulator of vascular contraction in both physiological states and pathologically obese mice. TRPV4 SMC contributes to the ontogeny of vasoconstriction and hypertension induced by TRPV4 SMC over-expression in obese mice mesenteric artery.

Human bone marrow-derived mesenchymal stem cells (hBMSCs) are promising candidates for stem cell therapy in clinical trials. Applications of hBMSCs in clinical therapy are limited by cellular senescence due to long-term ex vivo expansion. Metformin, an oral hypoglycemic drug for type 2 diabetes, has been shown to have antiaging effects. However, the mechanisms of metformin in antiaging treatment remain controversial. Here, we used D-galactose (D-gal) to establish an appropriate model of senescent hBMSCs to explore the antiaging effects of metformin. Following metformin treatment with a low concentration range, senescence phenotypes induced by D-gal significantly changed, including generation of reactive oxygen species (ROS), loss of mitochondrial membrane potential (MMP), and cell cycle arrest. In contrast, no apparent change was found in unsenescent hBMSCs. Furthermore, the results show that activation of 5 ′ AMP-activated protein kinase (AMPK) by metformin enhances cell autophagy in senescent hBMSCs. These findings suggest that metformin exerts antiaging function within the low concentration range by enhancing autophagy and exhibits potential benefits for clinical stem cell therapy by ameliorating the ex vivo replicative senescence of hBMSCs.

PURPOSE Chemoimmunotherapy for patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) is largely unchanged for decades. Both preclinical models and clinical data suggest the combination of lenalidomide and ibrutinib may have synergy in DLBCL, particularly in the non–germinal center B-cell-like subset. METHODS We enrolled 60 patients with newly diagnosed non–germinal center B-cell-like DLBCL in this investigator-initiated, single-arm phase II trial of rituximab, lenalidomide, and ibrutinib (RLI) with the sequential addition of chemotherapy (ClinicalTrials.gov identifier: NCT02636322 ). Patients were treated with rituximab 375 mg/m2 intravenous once on day 1, lenalidomide 25 mg once per day on days 1-10, and ibrutinib 560 mg once daily continuously of each 21-day cycle (RLI). After two cycles, standard chemotherapy was added to RLI for six additional cycles. The primary end points were overall response rate (ORR) after two cycles of RLI alone and complete response rate after completion of RLI with chemotherapy. In evaluable samples, circulating tumor DNA and DLBCL90 assays were performed. RESULTS The median age was 63.5 years (range, 29-83 years) with 28% age 70 years or older. The revised international prognostic index identified 42% as high risk, and 62% were double expressor of MYC and BCL2 protein. The ORR after two cycles of RLI was 86.2%, and the complete response rate at the end of RLI-chemotherapy was 94.5%. With a median follow-up of 31 months, the progression-free survival and overall survival were at 91.3% and 96.6% at 2 years, respectively. CONCLUSION Smart Start is the first study, to our knowledge, to treat newly diagnosed DLBCL with a targeted therapy combination before chemotherapy. RLI produced a high ORR, and RLI with chemotherapy resulted in durable responses. This establishes the potential for developing biologically driven and noncytotoxic first-line therapies for DLBCL.

A heteroanion self-assembly strategy for regulating the shape and expanding the size of the silver cluster from Ag37 to Ag46 with a macrocyclic (p-phenyl-thiacalix[4]arene) ligand has been presented.

A study designed different parameter schemes for a weather research and forecasting model to simulate hourly winter and summer wind speed and direction at a wind-farm tower in China. The schemes were found to reproduce the local wind conditions accurately and simulate wind direction very well. The results showed that one scheme performed better for the wind speed and wind direction simulation at 10 and 90 m height in the winter, while another performed better for simulation at 10 m height in the summer. The results for these schemes showed that the correlation coefficients of wind speed and wind direction were 0.75 and 0.62 in winter and 0.55 and 0.44 in summer, respectively. Overall, the parameterised model exhibited better simulation of the wind speed than wind direction, and was better in winter than in summer.

To explore the effect of time to remission on residual symptoms, functioning and quality of life (QOL) of the patients with major depressive disorder (MDD).A total of 434 patients were enrolled from 16 sites of China. The Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR) and self-rating scales were assessed at baseline, and months 1, 3 and 6. Baseline remitters were defined as those subjects with a QIDS-SR score ≤ 5 at baseline. Later remitters was defined as those reaching remission one month (Month 1 remitters) or three month (Month 3 remitters) after baseline. Persistent non-remitters were defined as those with QIDS-SR score 5 at all 3 assessments. A follow-up assessment was done at month 6 to examine outcomes. Cross-lagged models indicated QIDS-SR predicted social functioning and QOL.Totally, 179 patients at baseline achieved remission. An additional 141 participants remitted at month 1 (n = 94) or month 3 (n = 47), and 63 patients were persistent non-remitters. There were significant differences between all groups on depression severity at baseline. QOL was similar for both late remitter groups, which was better than non-remitters, but lower than early-remitters. Late remitters and non-remitters showed significant differences on change of functioning and QOL (P 0.001) at each visit. By 6 months, all remitting groups showed lower depression severity and better social functioning and QOL than persistent non-remitters. Cross-lagged models indicated QIDS-SR predicted social functioning and QOL.We confirmed the association of earlier remission with a better quality of remission at early stage; but the time to remission does not affect future functioning and QOL.

The designed WBE breaks the trade-off between water evaporation and salt resistance, achieving ultrahigh water evaporation capacity (3.02 kg m−2 h−1) and long-term salt resistance (continuous 100 h in 20 wt% brine) under 1 sun irradiation.

One-dimensional metal–organic coordination polymers show high proton conductivities and excellent stabilities, mainly attributable to the coordination interactions/abilities of metal ions.

Electrocatalytically active species of crystalline MOFs in a neutral OER process were identified as a mononuclear coordination compound and its isomer via a crystal-to-crystal transformation.

The development of a method for the large-scale and solvent-free preparation of hierarchical pore single-atom catalysts is highly desirable but challenging.

An endoplasmic reticulum targeting NIR fluorescent probe (ERBM) was developed for real-time monitoring of carboxylesterase 1 (CES1) and exhibited excellent ER location in living cell imaging. In addition, ERBM was applied to illustrate the regulation characteristics of CES1 under ER stress and acute liver injury models at the cell and animal level.

A novel near-infrared (NIR) fluorescent probe CHC-CES1 based on a hemi-cyanine skeleton for detecting carboxylesterase 1 (CES1) activity was developed and applied for the evaluation of pesticide toxicity.

An atomic source of 1 μg Sn was prepared by electrodeposition on 3 × 0.7 mm Re filament for LRIMS test. The average detection efficiency was almost 10 times higher than that after dropping the sample with graphene oxide.

Recently, the rs41291957 polymorphism in the promoter region of miR-143/145 has been repeatedly investigated for its contribution to cancer susceptibility. However, the results remain conflicting rather than conclusive, which calls for further investigations. Therefore, we here conducted a case-control study and meta-analysis to explore the association between rs41291957 and cancer risk. In the case-control study, a total of 2277 cancer patients (lung, liver, gastric and colorectal cancers) and 800 normal controls were recruited, the genotyping of rs41291957 was performed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Sanger sequencing. In the meta-analysis, 5 previously published studies and our present study were included, the STATA 14.0 software was applied to conduct all statistical analyses. The results of case-control study showed that rs41291957 was significantly associated with the risk of gastric cancer, colon cancer, rectal cancer, and colorectal cancer in Hubei Han Chinese population. The results of meta-analysis demonstrated that rs41291957 was significantly associated with overall cancer risk, especially colorectal cancer risk and lung cancer risk. Collectively, the rs41291957 polymorphism of miR-143/145 may be a plausible susceptible locus for cancer risk, which should be validated in future studies with larger samples in different ethnic populations.

Background: Few randomized controlled trials (RCTs) investigated the effects of mindfulness intervention on affective and cognitive symptoms in older adults with mild cognitive impairment (MCI). Furthermore, no RCTs on mindfulness followed participants beyond two years. Objective: To examine the longitudinal effects of a mindful awareness practice (MAP) intervention on depressive, anxiety, and cognitive symptoms in MCI. Methods: In this parallel-arm and assessor-blinded RCT, 55 community-dwelling older adults with MCI were randomized into the MAP or active control, i.e., health education program (HEP). Intervention sessions were conducted weekly for three months and monthly for the subsequent six months. Assessments and follow-up were conducted at baseline, 3-month, 9-month, and 5-year time points. Depressive, anxiety, and cognitive symptoms were measured using the Geriatric Depression Scale-15 (GDS-15), Geriatric Anxiety Inventory-20 (GAI-20), and Mini-Mental State Examination (MMSE), respectively. Linear-mixed models, following the intention-to-treat principle, were used for data analyses. Results: A total of 55 participants aged 60 to 86 (Mean age: 71.3±6 years old) was recruited, with n = 28 allocated to the MAP arm and n = 27 allocated to the HEP arm. Compared to HEP, GDS-15, GAI-20, and MMSE scores did not differ significantly in MAP during follow-ups. Conclusion: Compared to HEP, MAP did not improve affective symptoms nor delay deteriorations in general cognition in community-dwelling older adults with MCI. Compared to our previous findings showing domain-specific improvements in MAP over HEP in attention and memory up to 9 months, this study highlights the importance of examining domain-specificity using detailed cognitive measures in non-pharmacological intervention with MCI.

The growing interest to develop modern digital displays and colour printing has driven the advancement of colouration technologies with remarkable speed. In particular, metasurface-based structural colouration shows a remarkable high colour saturation, wide gamut palette, chiaroscuro presentation and polarization tunability. However, previous approaches cannot simultaneously achieve all these features. Here, we design and experimentally demonstrate a surface-relief plasmonic metasurface consisting of shallow nanoapertures that enable the independent manipulation of colour hue, saturation and brightness by individually varying the geometric dimensions and orientation of the nanoapertures. We fabricate microscale artworks using a reusable template-stripping technique that features photorealistic and stereoscopic impressions. In addition, through the meticulous arrangement of differently oriented nanoapertures, kaleidoscopic information states can be decrypted by particular combinations of incident and reflected polarized light.

The DArk Matter Particle Explorer (DAMPE) is well suitable for searching for monochromatic and sharp $\gamma$-ray structures in the GeV$-$TeV range thanks to its unprecedented high energy resolution. In this work, we search for $\gamma$-ray line structures using five years of DAMPE data. To improve the sensitivity, we develop two types of dedicated data sets (including the BgoOnly data which is the first time to be used in the data analysis for the calorimeter-based gamma-ray observatories) and adopt the signal-to-noise ratio optimized regions of interest (ROIs) for different DM density profiles. No line signals or candidates are found between 10 and 300 GeV in the Galaxy. The constraints on the velocity-averaged cross section for $\chi\chi \to \gamma\gamma$ and the decay lifetime for $\chi \to \gamma\nu$, both at 95% confidence level, have been calculated and the systematic uncertainties have been taken into account. Comparing to the previous Fermi-LAT results, though DAMPE has an acceptance smaller by a factor of $\sim 10$, similar constraints on the DM parameters are achieved and below 100 GeV the lower limits on the decay lifetime are even stronger by a factor of a few. Our results demonstrate the potential of high-energy-resolution observations on dark matter detection., Comment: 14 pages, 8 figures. Update the content to keep up with the published version

Based on the shield tunnel construction of the left line of Guowei road station-Qingshan lake west station of Nanchang metro line 3, the study focuses on the adverse effects of tunnel segment convergence and settlement deformation of vault and arch bottom on shield construction in the process of shield tunnel construction in water-rich complex stratum. The time-space curves of segment convergence and settlement value on typical monitoring sections are drawn, their variation laws are analyzed, and the deformation values of monitoring data are analyzed and tested. Based on the analysis results, the qualitative and quantitative evaluation of the overall or local deformation state of each monitoring object of tunnel segment is carried out. The results show that the cumulative deformation of each typical monitoring section is lower than the warning value, and the tunnel segment has a systematic offset in the horizontal and vertical directions of the clearance.