Background: Alzheimer’s disease (AD) presents a significant global health concern, characterized by neurodegeneration and cognitive decline. Neuroinflammation is a crucial factor in AD development and progression, yet effective pharmacotherapy remains elusive. Sulforaphane (SFN), derived from cruciferous vegetables and mainly from broccoli, has shown a promising effect via in vitro and in vivo studies as a potential treatment for AD. This study aims to investigate the possible prophylactic mechanisms of SFN against prefrontal cortex (PFC)-related recognition memory impairment induced by lipopolysaccharide (LPS) administration. Methodology: Thirty-six Swiss (SWR/J) mice weighing 18–25 g were divided into three groups (n = 12 per group): a control group (vehicle), an LPS group (0.75 mg/kg of LPS), and an LPS + SFN group (25 mg/kg of SFN). The total duration of the study was 3 weeks, during which mice underwent treatments for the initial 2 weeks, with daily monitoring of body weight and temperature. Behavioral assessments via novel object recognition (NOR) and temporal order recognition (TOR) tasks were conducted in the final week of the study. Inflammatory markers (IL-6 and TNF), antioxidant enzymes (SOD, GSH, and CAT), and pro-oxidant (MDA) level, in addition to acetylcholine esterase (AChE) activity and active (caspase-3) and phosphorylated (AMPK) levels, were evaluated. Further, PFC neuronal degeneration, Aβ content, and microglial activation were also examined using H&E, Congo red staining, and Iba1 immunohistochemistry, respectively. Results: SFN pretreatment significantly improved recognition memory performance during the NOR and TOR tests. Moreover, SFN was protected from neuroinflammation and oxidative stress as well as neurodegeneration, Aβ accumulation, and microglial hyperactivity. Conclusion: The obtained results suggested that SFN has a potential protective property to mitigate the behavioral and biochemical impairments induced by chronic LPS administration and suggested to be via an AMPK/caspase-3-dependent manner. Full article

Medulloblastomas (MBs) represent the most prevalent malignant solid tumors in kids. The conventional treatment regimen for MBs includes surgical removal of the tumor, followed by radiation and chemotherapy. However, this approach is associated with significant morbidity and detrimental side effects. Consequently, there is a critical demand for more precise and less harmful treatments to enhance the quality of life for survivors. CEP-18770, a novel proteasome inhibitor that targets the 20S subunit, has emerged as a promising candidate, due to its anticancer activity in metastatic solid tumors and multiple myeloma, coupled with an acceptable safety profile. In this study, we aimed to assess the anticancer efficacy of CEP-18770 by employing a variety of MB patient-derived cells and cell lines. Our preclinical investigations revealed that CEP-18770 effectively inhibits proteasome activity and induces apoptosis in MBs cells. Furthermore, we discovered that CEP-18770 and cisplatin, a current component of MB therapy, exhibit a synergistic apoptotic effect. This paper shows that CEP-18770 holds potential as an adjunctive treatment for MB tumors, thereby paving the way for more targeted and less toxic therapeutic strategies. Full article

The unprecedented reductions in anthropogenic emissions over the COVID-19 lockdowns were utilised to investigate the response of ozone (O₃) concentrations to changes in its precursors across various UK sites. Ozone, volatile organic compounds (VOCs) and NO_x (NO+NO₂) data were obtained for a 3-year period encompassing the pandemic period (January 2019–December 2021), as well as a pre-pandemic year (2017), to better understand the contribution of precursor emissions to O₃ fluctuations. Compared with pre-lockdown levels, NO and NO₂ declined by up to 63% and 42%, respectively, over the lockdown periods, with the most significant changes in pollutant concentrations recorded across the urban traffic sites. O₃ levels correspondingly increased by up to 30%, consistent with decreases in the [NO]/[NO₂] ratio for O₃ concentration response. Analysis of the response of O₃ concentrations to the NO_x reductions suggested that urban traffic, suburban background and suburban industrial sites operate under VOC-limited regimes, while urban background, urban industrial and rural background sites are NO_x-limited. This was in agreement with the [VOC]/[NO_x] ratios determined for the London Marylebone Road (LMR; urban traffic) site and the Chilbolton Observatory (CO; rural background) site, which produced values below and above 8, respectively. Conversely, [VOC]/[NO_x] ratios for the London Eltham (LE; suburban background) site indicated NO_x-sensitivity, which may suggest the [VOC]/[NO_x] ratio for O₃ concentration response may have had a slight NO_x-sensitive bias. Furthermore, O₃ concentration response with [NO]/[NO₂] and [VOC]/[NO_x] were also investigated to determine their relevance and accuracy in identifying O₃-NO_x-VOC relationships across UK sites. While the results obtained via utilisation of these metrics would suggest a shift in photochemical regime, it is likely that variation in O₃ during this period was primarily driven by shifts in oxidant (OX; NO₂ + O₃) equilibrium as a result of decreasing NO₂, with increased O₃ transported from Europe likely having some influence. Full article

Background: In an era of dramatic technological progress, the consequent economic transformations, and an increasing need for an adaptable workforce, the importance of education has risen to the forefront of the social discourse. The concurrent increase in the awareness of issues pertaining to social justice and the debate over what this justice entails and how it ought to be effected, feed into the education policy more than ever before. From the nexus of the aforementioned considerations, concern about the so-called education gap has emerged, with worldwide efforts to close it. Methods: I analyze the premises behind such efforts and demonstrate that they are founded upon fundamentally flawed ideas. Results: I show that in a society in which education is delivered equitably, education gaps emerge naturally as a consequence of differentiation due to talents, the tendency for matched mate selection, and the heritability of intellectual traits. Conclusion: I issue a call for a redirection of efforts away from the ill-founded idea of closing the education gap to the understanding of the magnitude of its unfair contributions, as well as to those social aspects that can modulate it in accordance with what a society deems fair according to its values. Full article

This paper considers the problem of admissibility and admissibilization of 2D singular continuous systems described by the Roesser model. A necessary and sufficient admissibility condition is first proposed for 2D singular continuous systems in terms of a strict Linear Matrix Inequality (LMI). Then, a necessary and sufficient condition is established for the closed-loop system to be admissible (i.e., stable, regular, and impulse-free). Moreover, the stability condition is completed to give a sufficient condition to ensure a specified H_∞ disturbance attenuation level for the state feedback closed loop. To illustrate the effectiveness of the proposed methodology, a numerical example is given to illustrate an admissibilization of a state feedback closed-loop system. Full article

The development of an advanced dye adsorbent that possesses a range of beneficial characteristics, such as high adsorption capacity, swift adsorption kinetics, selective adsorption capability, and robust reusability, remains a challenge. This study introduces a facile method for fabricating an amine-rich porous adsorbent (ARPA), which is specifically engineered for the adsorptive removal of anionic dyes from aqueous solutions. Through a comprehensive assessment, we have evaluated the adsorption performance of ARPA using two benchmark dyes: amaranth (ART) and tartrazine (TTZ). Our findings indicate that the adsorption process reaches equilibrium in a remarkably short timeframe of just 20 min, and it exhibits an excellent correlation with both the Langmuir isotherm model and the pseudo-second-order kinetic model. Furthermore, ARPA has demonstrated an exceptional maximum adsorption capacity, with values of 675.68 mg g⁻¹ for ART and 534.76 mg g⁻¹ for TTZ. In addition to its high adsorption capacity, ARPA has also shown remarkable selectivity, as evidenced by its ability to selectively adsorb TTZ from a mixed dye solution, a feature that is highly desirable for practical applications. Beyond its impressive adsorption capabilities, ARPA can be efficiently regenerated and recycled. It maintains a high level of original removal efficiency for both ART (76.8%) and TTZ (78.9%) even after five consecutive cycles of adsorption and desorption. Considering the simplicity of its synthesis and its outstanding adsorption performance, ARPA emerges as a highly promising material for use in dye removal applications. Consequently, this paper presents a straightforward and feasible method for the production of an effective dye adsorbent for environmental remediation. Full article

Homosexual (lesbian or gay) and bisexual (i.e., LGB) people tend to suffer from social exclusion and thus distress. To prevent or relieve distress, the people’s assertiveness about justice and rights is an advocated means, but its effectiveness is uncertain, considering possible conflict with social exclusion. To clarify the effectiveness, this study analyzed data collected from 189 Chinese LGB adults in Hong Kong, which is a special administrative region of China generally Westernized and liberal to sexual orientation. Controlling for prior distress reported, the analysis showed that distress was lower when assertiveness was higher or social exclusion experienced was lower. However, distress was higher when both assertiveness and social exclusion experienced were higher. The higher distress implies a conflict between assertiveness and social exclusion to raise distress. It also implies the need to avoid conflict when promoting assertiveness and eliminating social exclusion to prevent distress in LGB people. Full article

A biotope map provides ecological and spatial information that reflects the natural and ecological features and values of a city. In South Korea, efforts have been made to create a map that includes grades based on evaluating the ecological value of a specific surface space. However, plans for applications have not been established, except for development restrictions or regulations for biotopes with high ecological value ratings. The aim of this study was to promote environmentally friendly and sustainable urban management through ecological land use management for all biotope types that are influenced by anthropogenic land use. Strategies for maintenance, protection, recovery, improvement, creation, and reduction based on ecological restoration principles were set as management goals. To achieve these management goals, evaluation items and indicators were suggested for minor-classification types and applied to Dongducheon City. Management strategies were suggested for target sites based on grades and thematic maps of biotope types to be utilized, such as urban ecological axes, river naturality restoration, and wetland and forest preservation. These findings support sustainable and environmentally friendly urban development by providing fundamental data for ecological and environmental management, including the preservation and restoration of natural environments and the creation of urban ecological networks. Full article

Heat transfer affects a motor’s sizing, its performance, and, ultimately, the overall vehicle’s range and endurance. However, the thermal literature does not have early-stage models for outrunner brushless DC (BLDC) motors found in small unmanned aerial systems (UASs). To address this gap, we have developed a non-dimensional heat transfer model (Nusselt correlation). Parametric experiments of four different-sized BLDC motors under load in Reynolds-matched wind tunnel tests generated data for model correlation. The motors’ aspect ratios (diameter/length) ranged from 0.9 to 1.5. The freestream Reynolds number of the axial flow over the motors ranged from 20,000 to 40,000. The rotational Reynolds number ranged from 10,000 to 20,000. The results showed that aspect ratio had the largest influence on heat transfer, followed by rotational and freestream Reynolds numbers. A steady-state model used the correlation to predict the motor’s ambient temperature differential within 10 K of experimental data. A case study applied the correlation to predict a hypothetical motor’s continuous torque in different environments. The correlation enables conceptual designers to capture thermally-driven trade-offs in early design stages and reduce costly revisions in later stages. Full article

This retrospective multicenter study examines therapy-induced orbital and ocular MRI findings in retinoblastoma patients following selective intra-arterial chemotherapy (SIAC) and quantifies the impact of SIAC on ocular and optic nerve growth. Patients were selected based on medical chart review, with inclusion criteria requiring the availability of posttreatment MR imaging encompassing T2-weighted and T1-weighted images (pre- and post-intravenous gadolinium administration). Qualitative features and quantitative measurements were independently scored by experienced radiologists, with deep learning segmentation aiding total eye volume assessment. Eyes were categorized into three groups: eyes receiving SIAC (Rb-SIAC), eyes treated with other eye-saving methods (Rb-control), and healthy eyes. The most prevalent adverse effects post-SIAC were inflammatory and vascular features, with therapy-induced contrast enhancement observed in the intraorbital optic nerve segment in 6% of patients. Quantitative analysis revealed significant growth arrest in Rb-SIAC eyes, particularly when treatment commenced ≤ 12 months of age. Optic nerve atrophy was a significant complication in Rb-SIAC eyes. In conclusion, this study highlights the vascular and inflammatory adverse effects observed post-SIAC in retinoblastoma patients and demonstrates a negative impact on eye and optic nerve growth, particularly in children treated ≤ 12 months of age, providing crucial insights for clinical management and future research. Full article

Background: Due to lower age thresholds for cataract surgery and increased longevity, cases with intraocular lens (IOL) dislocation requiring removal have increased. Traditional methods, such as cutting or folding the IOL within the eye, pose a high risk of complications, including corneal endothelial and iris damage. Methods: We developed a new minimally invasive technique for direct IOL removal using specially designed lens-grabbing forceps. These forceps can grasp and remove the IOL through a small incision in a single motion, significantly reducing intraocular manipulations compared to conventional methods. Results: In our test cases, IOL removal through a 2.2 mm corneal incision was completed in approximately 95 s, with minimal incision enlargement (about 0.16 mm) and a slight decrease in corneal endothelial cells. Conclusions: Our findings suggest that this technique is minimally invasive and safe for IOL removal, offering a promising alternative to existing methods. Full article

The purpose of this mixed-method study was to (1) examine the effect of an adapted physical activity program, Fitness Access McGill (FAM), on leisure-time physical activity (LTPA), autonomous and controlled motivation, and the basic psychological needs of self-determination theory among university students/staff with a physical disability and/or chronic conditions, and (2) explore participants’ experiences after completing FAM. Nineteen participants completed validated questionnaires for all study outcomes pre- and post-FAM. Nine participants partook in a 30–60 min semi-structured interview conducted within three months of completing FAM. Quantitative data were analyzed using repeated measures effect size calculations. Qualitative data were analyzed using directed content analysis. Participants reported an increase in total LTPA (dRMpooled = 0.58), with the greatest positive change on strenuous intensity (dRMpooled = 0.81). Large effects were found for changes in autonomous motivation (dRMpooled = 0.52), autonomy (dRMpooled = 0.79), competence (dRMpooled = 0.79), and relatedness (dRMpooled = 0.89). Participants reported FAM being supportive towards their psychological needs, the development of a LTPA routine, and enhanced overall well-being. Future research can be built upon this study to develop a robust understanding as to how need-supportive, adapted LTPA programs could be implemented within community settings or out-patient rehabilitation to support exercise engagement, physical health and overall well-being among adults with disabilities. Full article

The removal of dental plaque from the gingival margins of the teeth is essential to maintaining periodontal health. Whilst it has been established that electric toothbrushes demonstrate a greater ability to remove plaque, no systematic review has specifically investigated which technology is better for removing plaque from the interdental tooth surfaces, where plaque control may be more difficult. Three databases were searched until October 2023: MEDLINE and DOSSS via EBSCOhost and Embase. Data extraction was carried out on studies which met the inclusion criteria, and a risk of bias assessment was completed. The study findings were combined via a narrative synthesis and a meta-analysis where appropriate. A total of 77 studies were found, out of which 14 were selected and included in the analysis. The mean difference in interproximal plaque reduction, measured using the Rustogi Modified Naval Plaque Index (RMNPI) at 8 weeks, was 0.09 (p < 0.00001) in favor of the oscillating–rotating toothbrush. At 6 and 12 weeks, the mean difference in plaque reduction (RMNPI) was 0.05 (p = 0.0008) and 0.04 (p = 0.0001) in favor of the oscillating–rotating toothbrush, respectively. The studies show a tendency for oscillating–rotating toothbrushes to remove more interproximal plaque than oscillating toothbrushes, especially in a short time (8 weeks). Full article

Atherosclerosis is closely associated with metabolic disorders such as cholesterol accumulation, bile acid metabolism, and gut dysbiosis. Neoagarotetraose supplementation has been shown to inhibit obesity and alleviate type 2 diabetes, but its effects on modulating the development of atherosclerosis remain unexplored. Therefore, the present study was conducted to investigate the protective effects and potential mechanisms of neoagarotetraose on high-fat, high-cholesterol diet (HFHCD)-induced atherosclerosis in ApoE^−/− mice. The results showed that neoagarotetraose supplementation decreased the atherosclerotic lesion area by 50.1% and the aortic arch lesion size by 80.4% compared to the HFHCD group. Furthermore, neoagarotetraose supplementation led to a significant reduction in hepatic lipid content, particularly non-high-density lipoprotein cholesterol. It also resulted in a substantial increase in total bile acid content in both urine and fecal samples by 3.0-fold and 38.7%, respectively. Moreover, neoagarotetraose supplementation effectively downregulated the intestinal farnesoid X receptor by 35.8% and modulated the expressions of its associated genes in both the liver and intestine. In addition, correlation analysis revealed strong associations between gut microbiota composition and fecal bile acid levels. These findings highlight the role of gut microbiota in neoagarotetraose-mitigating atherosclerosis in HFHCD-fed ApoE^−/− mice. This study indicates the potential of neoagarotetraose as a functional dietary supplement for the prevention of atherosclerosis. Full article

Colorectal cancer (CRC) currently ranks as the third most common cancer and the second leading cause of cancer-related deaths worldwide, posing a significant global health burden to the population. Recent studies have reported the emergence of a new clinical picture of the disease, with a notable increase in CRC rates in younger populations of <50 years of age. The American Cancer Society (ACS) now recommends CRC screening starting at age 45 for average-risk individuals. Dr. Aasma Shaukat’s Keynote Conference highlights the critical need for updated screening strategies, with an emphasis on addressing the suboptimal adherence rates and the effective management of the growing burden of CRC. Lowering the adenoma detection screening age can facilitate early identification of adenomas in younger asymptomatic patients, altering the epidemiologic landscape. However, its implications may not be as profound unless a drastic shift in the age distribution of CRC is observed. Currently, various screening options are available in practice, including stool-based tests like multitarget stool DNA (mtDNA) tests, fecal immunochemical testing (FIT), and imaging-based tests. In addition to existing screening methods, blood-based tests are now emerging as promising tools for early CRC detection. These tests leverage innovative techniques along with AI and machine learning algorithms, aiding in tumor detection at a significantly earlier stage, which was not possible before. Medicare mandates specific criteria for national coverage of blood-based tests, including sensitivity ≥ 74%, specificity ≥ 90%, FDA approval, and inclusion in professional society guidelines. Ongoing clinical trials, such as Freenome, Guardant, and CancerSEEK, offer hope for further advancements in blood-based CRC screening. The development of multicancer early detection tests like GRAIL demonstrates a tremendous potential for detecting various solid tumors and hematologic malignancies. Despite these breakthroughs, the question of accessibility and affordability still stands. The ever-evolving landscape of CRC screening reflects the strength of the scientific field in light of an altered disease epidemiology. Lowering screening age along with the integration of blood-based tests with existing screening methods holds great potential in reducing the CRC-related burden. At the same time, it is increasingly important to address the challenges of adaptation of the healthcare system to this change in the epidemiologic paradigm. Full article

Based on the WindPACT-3MW wind turbine tower commonly used in wind power engineering, a finite element model (FEM) of a hybrid wind turbine tower combining an upper steel tube with a lower steel truss is designed and established. On this basis, a static optimization analysis, wind-induced vibration analysis, and fatigue life analysis of the hybrid tower structure are performed. The results show that under the same design parameters, the overall stiffness and static bearing capacity of the tower structure can be significantly improved by using subdivided truss webs, increasing the truss height as much as possible and increasing the width of the truss base appropriately. Under normal operation conditions, the response of the tower structure in the along-wind direction is significantly greater than the response in the crosswind direction, indicating that the aerodynamic thrust generated by the rotation of the blades is the main factor causing the wind-induced vibration of the tower structure. For the tower structure analyzed in this study, when considering the entire range of wind speeds from the cut-in wind speed to the cut-out wind speed, the fatigue life of the structure is 38.5 years. Full article

The hyperspectral image (HSI) distinguishes itself in material identification through its exceptional spectral resolution. However, its spatial resolution is constrained by hardware limitations, prompting the evolution of HSI super-resolution (SR) techniques. Single HSI SR endeavors to reconstruct high-spatial-resolution HSI from low-spatial-resolution inputs, and recent progress in deep learning-based algorithms has significantly advanced the quality of reconstructed images. However, convolutional methods struggle to extract comprehensive spatial and spectral features. Transformer-based models have yet to harness long-range dependencies across both dimensions fully, thus inadequately integrating spatial and spectral data. To solve the above problem, in this paper, we propose a new HSI SR method, SSAformer, which merges the strengths of CNNs and Transformers. It introduces specially designed attention mechanisms for HSI, including spatial and spectral attention modules, and overcomes the previous challenges in extracting and amalgamating spatial and spectral information. Evaluations on benchmark datasets show that SSAformer surpasses contemporary methods in enhancing spatial details and preserving spectral accuracy, underscoring its potential to expand HSI’s utility in various domains, such as environmental monitoring and remote sensing. Full article

In response to the escalating concern over the effect of environmental factors on ocular health, this study aimed to investigate the impact of air pollution-associated particulate matter (PM) on ocular allergy and inflammation. C57BL/6 mice were sensitized with ovalbumin (OVA) topically and aluminum hydroxide via intraperitoneal injection. Two weeks later, the mice were challenged with OVA and exposed to PM. Three groups—naive, OVA, and OVA-sensitized with PM exposure (OVA + PM) groups—were induced to an Allergic Eye disease (AED) model. Parameters including clinical signs, histological changes, inflammatory cell infiltration, serum OVA-specific immunoglobulins E (IgE) levels, mast cells degranulation, cellular apoptosis and T-cell cytokines were studied. The results demonstrate that exposure with PM significantly exacerbates ocular allergy, evidenced by increased eye-lid edema, mast cell degranulation, inflammatory cytokines (IL-4, IL-5 and TNF-α), cell proliferation (Ki67), and serum IgE, polymorphonuclear leukocytes (PMN), and apoptosis and reduced goblet cells. These findings elucidate the detrimental impact of PM exposure on exacerbating the severity of AED. Noticeably, diminished goblet cells highlight disruptions in ocular surface integrity, while increased PMN infiltration with an elevated production of IgE signifies a systemic allergic response with inflammation. In conclusion, this study not only scientifically substantiates the association between air pollution, specifically PM, and ocular health, but also underscores the urgency for further exploration and targeted interventions to mitigate the detrimental effects of environmental pollutants on ocular surfaces. Full article

Anaerobic digestion (AD) is a biological process that occurs in the limited presence of oxygen. This process involves various difficulties during the operation, such as acidification and increased concentration of volatile fatty acids, which can inhibit methane production. Therefore, in this work, the impact of biochar on the co-digestion of untreated sludge and residual biomass under mesophilic conditions was studied. For the production of biochar, the gasification process was used at different temperatures: 759 °C (BL), 798 °C (BM), and 888 °C (BH). This biochar was added in concentrations of 0 g/L, 3.33 g/L, and 6.67 g/L at the beginning of the co-digestion process. The results showed that a concentration of 6.67 g/L with BH biochar increased the PBM by 18% compared to the control sample and reduced the chemical oxygen demand (COD) by 88%. In addition, there was a reduction of volatile fatty acids (VFA) of 42.75%. Furthermore, FTIR analysis demonstrated that biochar has appropriate functional groups for this process. These data suggest a good interaction of biochar with the mixture of sludge and municipal waste, indicating that biochar can improve the anaerobic co-digestion of untreated sludge and municipal waste. Full article

Narrowband afterglow materials display interesting functions in high-quality anti-counterfeiting and multiplexed bioimaging. However, there is still a limited exploration of these afterglow materials, especially for those with a full width at half maxima (FWHM) around 30 nm. Here, we report the fabrication of narrowband organic/inorganic hybrid afterglow materials via energy transfer technology. Coronene (Cor) with a long phosphorescence feature and broad phosphorescence band is selected as the donor for energy transfer, and inorganic quantum dots (QDs) of CdSe/ZnS with a narrowband emission are used as acceptors. Upon doping into the organic matrix, the resultant three-component materials exhibit a narrowband afterglow with an afterglow lifetime of approximately 3.4 s and an FWHM of 31 nm. The afterglow wavelength of the afterglow materials can be controlled by the QDs. This work based on organic/inorganic hybrids provides a facile approach for developing multicolor and narrowband afterglow materials, as well as opens a new way for expanding the features of organic afterglow for multifunctional applications. It is expected to rely on narrowband afterglow emitters to solve the “spectrum congestion” problem of high-density information storage in optical anti-counterfeiting and information encryption. Full article

This study was conducted to compare and analyze whether Pilates exercise and yoga exercise help improve the performance of female fencers and prevent injury, and the dynamic balance test (LQ-YBT) and functional movement screening (FMS) test score of the elite adult female fencers were compared and analyzed as evaluation indicators. Participants were randomly classified into Pilates (n = 10) and yoga groups (n = 10), members of which took part in 50 min of exercise (5 min of warm-up, 40 min of main exercise, and 5 min of cool-down) twice weekly for eight weeks. The results obtained from this study were analyzed via independent t-test and 2-way ANOVA. The results were as follows: LQ-YBT measures (reaching distance) increased significantly for both groups, as did FMS scores (deep squat, hurdle step, inline lunge, shoulder mobility, active straight-leg raise, trunk-stability push-up, and rotary stability). These results suggest that Pilates exercise and yoga exercise might be likely effective in improving the performance of adult female fencers and injury prevention by increasing their dynamic balance ability and functional movement. Full article

In this paper, the notion of a cohesive and self-sufficient grid is proposed. Based on a cohesive and self-sufficient virtual microgrid, an active distribution network is optimally planned, and an optimal configuration of demand-side resources, distributed generations, and energy storage systems are generated. To cope with stochastic uncertainty from forecast error in wind speed and load, flexibility reserves are needed. In this paper, the supply relation between flexibility and uncertainty is quantified and integrated in an innovative index which is defined as cohesion. The optimization objectives are a minimized operational cost and system net-ability cohesion as well as self-sufficiency, which is defined as the abilities both to supply local load and to deal with potential uncertainty. After testing the optimal configuration in the PG&E 69 bus system, it is found that with a more cohesive VM partition, the self-sufficiency of VMs is also increased. Also, a case study on uncertainty-caused system imbalance is carried out to show how flexibility resources are utilized in real-time operational balance. Full article