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Phosphatidylinositol 4‐phosphate 5‐kinase (PIP5K) family members generate phosphatidylinositol 4,5‐bisphosphate (PIP2), a critical lipid regulator of diverse physiological processes. The PIP5K‐dependent PIP2 generation can also act upstream of the oncogenic phosphatidylinositol 3‐kinase (PI3K)/Akt pathway. Many studies have demonstrated various mechanisms of spatiotemporal regulation of PIP5K catalytic activity. However, there are few studies on regulation of PIP5K protein stability. Here, we examined potential regulation of PIP5Kα, a PIP5K isoform, via ubiquitin‐proteasome system, and its implication for breast cancer. Our results showed that the ubiquitin ligase NEDD4 (neural precursor cell expressed, developmentally down‐regulated gene 4) mediated ubiquitination and proteasomal degradation of PIP5Kα, consequently reducing plasma membrane PIP2 level. NEDD4 interacted with the C‐terminal region and ubiquitinated the N‐terminal lysine 88 in PIP5Kα. In addition, PIP5Kα gene disruption inhibited epidermal growth factor (EGF)‐induced Akt activation and caused significant proliferation defect in breast cancer cells. Notably, PIP5Kα K88R mutant that was resistant to NEDD4‐mediated ubiquitination and degradation showed more potentiating effects on Akt activation by EGF and cell proliferation than wild‐type PIP5Kα. Collectively, these results suggest that PIP5Kα is a novel degradative substrate of NEDD4 and that the PIP5Kα‐dependent PIP2 pool contributing to breast cancer cell proliferation through PI3K/Akt activation is negatively controlled by NEDD4.

Two lanthanide metal–organic frameworks [Ln-MOFs, Ln = Eu(III), Tb(III)] composed of oxalic acid and Ln building units were hydrothermally synthesized and fully characterized by powder X-ray diffraction, Fourier-transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscope, and energy-dispersive X-ray spectroscopy. Furthermore, their magnetic susceptibility measurements were obtained using SQUID based vibrating sample magnetometer (MPMS 3, Quantum Design). Both Ln-MOFs exhibited highly efficient luminescent property. Solid-state photoluminescence (PL) measurements revealed phosphorescence emission bands of Eu-MOF and Tb-MOF centered at 618 nm (red emission) and 550 nm (green emission) upon excitation at 396 nm and 285 nm, respectively. Eu-MOF and Tb-MOF displayed a phosphorescence quantum yield of 53% and 40%, respectively. Time-resolved PL analyses showed very long lifetime values, at 600 and 1065 ± 1 µs for Eu-MOF and Tb-MOF, respectively. Calculations performed by density functional theory indicated a charge transfer form metal centres to the ligand which was in good agreement with the experimental studies. Therefore, this new mode of highly photoluminescent MOF materials is studied for the first time which paves the way for better understanding of these systems for potential applications.

Phosphatidylinositol 4‐phosphate 5‐kinase ( PIP 5K) family members generate phosphatidylinositol 4,5‐bisphosphate ( PIP 2), a critical lipid regulator of diverse physiological processes. The PIP 5K‐dependent PIP 2 generation can also act upstream of the oncogenic phosphatidylinositol 3‐kinase ( PI 3K)/Akt pathway. Many studies have demonstrated various mechanisms of spatiotemporal regulation of PIP 5K catalytic activity. However, there are few studies on regulation of PIP 5K protein stability. Here, we examined potential regulation of PIP 5Kα, a PIP 5K isoform, via ubiquitin‐proteasome system, and its implication for breast cancer. Our results showed that the ubiquitin ligase NEDD 4 (neural precursor cell expressed, developmentally down‐regulated gene 4) mediated ubiquitination and proteasomal degradation of PIP 5Kα, consequently reducing plasma membrane PIP 2 level. NEDD 4 interacted with the C‐terminal region and ubiquitinated the N‐terminal lysine 88 in PIP 5Kα. In addition, PIP 5Kα gene disruption inhibited epidermal growth factor ( EGF )‐induced Akt activation and caused significant proliferation defect in breast cancer cells. Notably, PIP 5Kα K88R mutant that was resistant to NEDD 4‐mediated ubiquitination and degradation showed more potentiating effects on Akt activation by EGF and cell proliferation than wild‐type PIP 5Kα. Collectively, these results suggest that PIP 5Kα is a novel degradative substrate of NEDD 4 and that the PIP 5Kα‐dependent PIP 2 pool contributing to breast cancer cell proliferation through PI 3K/Akt activation is negatively controlled by NEDD 4.

Effect of Co substitution on Mn\\(_3\\)Ga is investigated using first-principles study for structural and magnetic properties. Without Co, ferrimagnetic Heusler compound Mn3Ga is in tetragonal phase. With Co substitution, depending on Co concentration (x) Mn\\(_3\\)Ga prefers tetragonal (cubic) phase when x \\leq 0.5 (x \\geq 0.5). Ferrimagnetism is robust regardless of x in both phases. While magnetic moments of two Mn do not vary significantly with x, Co magnetic moment in two phases exhibit different behaviors, leading to distinct features in total magnetic moment (M_{tot}). When x \\leq 0.5, in tetragonal phase, Co magnetic moment is vanishingly small, resulting in a decrease of M_{tot} with x. In contrast, when x \\geq 0.5, in cubic phase, Co magnetic moment is roughly 1\\(\\mu_B\\), which is responsible for an increase of Mtot. Electronic structure is analyzed with partial density of states for various x. To elucidate the counterintuitively small Co moment, the magnetic exchange interaction is investigated where exchange coefficient between Co and Mn is much smaller in x \\leq 0.5 case than x \\geq 0.5 one.

Achieving temporally precise, noninvasive control over specific neural cell types in the deep brain would advance the study of nervous system function. Here we use the potent channelrhodopsin ChRmine to achieve transcranial photoactivation of defined neural circuits, including midbrain and brainstem structures, at unprecedented depths of up to 7 mm with millisecond precision. Using systemic viral delivery of ChRmine, we demonstrate behavioral modulation without surgery, enabling implant-free deep brain optogenetics. Optogenetic control of neural activity in the deep brain is achieved without intracranial surgery using ChRmine.

Background Vietnam is undergoing a rapid epidemiological transition with a considerable burden of non-communicable diseases (NCDs), especially hypertension and diabetes (T2DM). Continuity of care (COC) is widely acknowledged as a benchmark for an efficient health system. This study aimed to determine the COC level for hypertension and T2DM within and across care levels and to investigate its associations with health outcomes and disease control. Methods A cross-sectional study was conducted on 602 people with T2DM and/or hypertension managed in primary care settings. We utilized both the Nijmegen continuity of care questionnaire (NCQ) and the Bice - Boxerman continuity of care index (COCI) to comprehensively measure three domains of COC: interpersonal, informational, and management continuity. ANOVA, paired-sample t-test, and bivariate and multivariable logistic regression analysis were performed to examine the predictors of COC. Results Mean values of COC indices were: NCQ: 3.59 and COCI: 0.77. The proportion of people with low NCQ levels was 68.8%, and that with low COCI levels was 47.3%. Primary care offered higher informational continuity than specialists ( p  < 0.01); management continuity was higher within the primary care team than between primary and specialist care ( p  < 0.001). Gender, living areas, hospital admission and emergency department encounters, frequency of health visits, disease duration, blood pressure and blood glucose levels, and disease control were demonstrated to be statistically associated with higher levels of COC. Conclusions Continuity of primary care is not sufficiently achieved for hypertension and diabetes mellitus in Vietnam. Strengthening robust primary care services, improving the collaboration between healthcare providers through multidisciplinary team-based care and integrated care approach, and promoting patient education programs and shared decision-making interventions are priorities to improve COC for chronic care.

This article examines whether mobile money adoption contributes to women’s economic empowerment, and considers the mediating effect of financial management behavior. Cross-sectional data analysis is conducted utilizing a sample of women in seven countries across South Asia and Sub-Saharan Africa. We also investigate whether these effects vary between rural and urban areas. Three measures of mobile money adoption are considered to reflect the process of engaging in mobile money services. We find supportive evidence for the impact of mobile money adoption on women’s economic empowerment and the influencing mechanism of financial management behavior for the whole sample and the rural sub-sample. Moreover, the results are consistent for three alternative measures of mobile money adoption. Our findings suggest that mobile money can be harnessed to promote women’s economic empowerment; however, the impact appears to be greater if women are equipped with proper financial management skills.

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk–outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk–outcome pairs, and new data on risk exposure levels and risk–outcome associations. We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk–outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. In 2017, 34·1 million (95% uncertainty interval [UI] 33·3–35·0) deaths and 1·21 billion (1·14–1·28) DALYs were attributable to GBD risk factors. Globally, 61·0% (59·6–62·4) of deaths and 48·3% (46·3–50·2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10·4 million (9·39–11·5) deaths and 218 million (198–237) DALYs, followed by smoking (7·10 million [6·83–7·37] deaths and 182 million [173–193] DALYs), high fasting plasma glucose (6·53 million [5·23–8·23] deaths and 171 million [144–201] DALYs), high body-mass index (BMI; 4·72 million [2·99–6·70] deaths and 148 million [98·6–202] DALYs), and short gestation for birthweight (1·43 million [1·36–1·51] deaths and 139 million [131–147] DALYs). In total, risk-attributable DALYs declined by 4·9% (3·3–6·5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23·5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18·6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning. Bill & Melinda Gates Foundation and Bloomberg Philanthropies.

In the contemporary landscape of power systems, the escalating integration of renewable energy resources and electric vehicle infrastructures into distribution networks has intensified the imperative to ensure power quality, operational optimization, and system reliability. Distribution network reconfiguration emerges as a pivotal strategy to mitigate power losses, facilitate the seamless assimilation of renewable generation, and regulate the charging and discharging dynamics of EVs, thereby constituting a critical endeavor in modern electrical engineering. While the Particle Swarm Optimization algorithm is renowned for its rapid convergence and effective exploitation of solution spaces, its capacity to thoroughly explore complex search domains remains limited, particularly in multifaceted optimization challenges. Conversely, the Grey Wolf Optimization algorithm excels in global exploration, offering robust mechanisms to circumvent local optima traps. Leveraging the complementary strengths of these approaches, this study proposes a hybrid PSO-GWO framework to address the distribution network reconfiguration problem, explicitly accounting for the integration of renewable energy sources and EV systems. Empirical validation, conducted on the IEEE 33-bus test system across diverse operational scenarios, underscores the efficacy of the proposed methodology, revealing exceptional precision and dependability. Notably, the approach achieves substantial reductions in power losses during peak demand periods with distributed generation incorporation while maintaining voltage profiles within the stringent operational bounds of 0.94 to 1.0 per unit, thus ensuring stability amidst variable load conditions. Comparative analyses further demonstrate that the hybrid method surpasses conventional optimization techniques, as evidenced by enhanced convergence rates and superior objective function outcomes. These findings affirm the proposed strategy as a potent tool for advancing the resilience and efficiency of next-generation distribution networks.

This study reports for the first time on the synthesis of novel resin@P-Ag 2 O material and its application for reducing the chloride effect on COD determination of high salinity water. This engineered core–shell nanomaterial with cationic ion exchange resin core and porous Ag 2 O shell was prepared by facile ion exchange and silver oxidation method at ambient temperature without using toxic chemicals. The material was characterized by FTIR, XRD, SEM, and SEM–EDX mapping. In the chloride removal test, this material gave a high adsorption capacity of ca. 244 mgCl/gAg at the mild condition with high durability after several adsorption–desorption cycles. Moreover, resin@P-Ag 2 O was applied for removing chloride in water to improve the accuracy of the SMEWW 5220C:2012 method for COD determination of high salinity water. The result showed that the COD of a water sample with salt content after being treated by the material had a low error (≤ 10%) as compared to the sample without salt. Meanwhile, the COD of salty water measured by the dilution method had an error of around 15%. These results indicate that resin@P-Ag 2 O material has a very potential application for chloride removal and COD determination of high salinity water.