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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.

To assess the role of in-flight transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we investigated a cluster of cases among passengers on a 10-hour commercial flight. Affected persons were passengers, crew, and their close contacts. We traced 217 passengers and crew to their final destinations and interviewed, tested, and quarantined them. Among the 16 persons in whom SARS-CoV-2 infection was detected, 12 (75%) were passengers seated in business class along with the only symptomatic person (attack rate 62%). Seating proximity was strongly associated with increased infection risk (risk ratio 7.3, 95% CI 1.2-46.2). We found no strong evidence supporting alternative transmission scenarios. In-flight transmission that probably originated from 1 symptomatic passenger caused a large cluster of cases during a long flight. Guidelines for preventing SARS-CoV-2 infection among air passengers should consider individual passengers' risk for infection, the number of passengers traveling, and flight duration.

Comprehensive profiling of actionable mutations in non-small cell lung cancer (NSCLC) is vital to guide targeted therapy, thereby improving the survival rate of patients. Despite the high incidence and mortality rate of NSCLC in Vietnam, the actionable mutation profiles of Vietnamese patients have not been thoroughly examined. Here, we employed massively parallel sequencing to identify alterations in major driver genes ( EGFR , KRAS, NRAS, BRAF , ALK and ROS1 ) in 350 Vietnamese NSCLC patients. We showed that the Vietnamese NSCLC patients exhibited mutations most frequently in EGFR (35.4%) and KRAS (22.6%), followed by ALK (6.6%), ROS1 (3.1%), BRAF (2.3%) and NRAS (0.6%). Interestingly, the cohort of Vietnamese patients with advanced adenocarcinoma had higher prevalence of EGFR mutations than the Caucasian MSK-IMPACT cohort. Compared to the East Asian cohort, it had lower EGFR but higher KRAS mutation prevalence. We found that KRAS mutations were more commonly detected in male patients while EGFR mutations was more frequently found in female. Moreover, younger patients (<61 years) had higher genetic rearrangements in ALK or ROS1 . In conclusions, our study revealed mutation profiles of 6 driver genes in the largest cohort of NSCLC patients in Vietnam to date, highlighting significant differences in mutation prevalence to other cohorts.

Evaluating the prognosis of patients with aneurysmal subarachnoid hemorrhage (aSAH) who may be at risk of poor outcomes using grading systems is one way to make a better decision on treatment for these patients. This study aimed to compare the accuracy of the modified World Federation of Neurosurgical Societies (WFNS), WFNS, and Hunt and Hess (H&H) Grading Scales in predicting the outcomes of patients with aSAH. From August 2019 to June 2021, we conducted a multicenter prospective cohort study on adult patients with aSAH in three central hospitals in Hanoi, Vietnam. The primary outcome was the 90-day poor outcome, measured by a score of 4 (moderately severe disability) to 6 (death) on the modified Rankin Scale (mRS). We calculated the areas under the receiver operator characteristic (ROC) curve (AUROCs) to determine how well the grading scales could predict patient prognosis upon admission. We also used ROC curve analysis to find the best cut-off value for each scale. We compared AUROCs using Z-statistics and compared 90-day mean mRS scores among intergrades using the pairwise multiple-comparison test. Finally, we used logistic regression to identify factors associated with the 90-day poor outcome. Of 415 patients, 32% had a 90-day poor outcome. The modified WFNS (AUROC: 0.839 [95% confidence interval, CI: 0.795-0.883]; cut-off value[greater than or equal to]2.50; P.sub.AUROC <0.001), WFNS (AUROC: 0.837 [95% CI: 0.793-0.881]; cut-off value[greater than or equal to]3.5; P.sub.AUROC <0.001), and H&H scales (AUROC: 0.836 [95% CI: 0.791-0.881]; cut-off value[greater than or equal to]3.5; P.sub.AUROC <0.001) were all good at predicting patient prognosis on day 90.sup.th after ictus. However, there were no significant differences between the AUROCs of these scales. Only grades IV and V of the modified WFNS (3.75 [standard deviation, SD: 2.46] vs 5.24 [SD: 1.68], p = 0.026, respectively), WFNS (3.75 [SD: 2.46] vs 5.24 [SD: 1.68], p = 0.026, respectively), and H&H scales (2.96 [SD: 2.60] vs 4.97 [SD: 1.87], p<0.001, respectively) showed a significant difference in the 90-day mean mRS scores. In multivariable models, with the same set of confounding variables, the modified WFNS grade of III to V (adjusted odds ratio, AOR: 9.090; 95% CI: 3.494-23.648; P<0.001) was more strongly associated with the increased risk of the 90-day poor outcome compared to the WFNS grade of IV to V (AOR: 6.383; 95% CI: 2.661-15.310; P<0.001) or the H&H grade of IV to V (AOR: 6.146; 95% CI: 2.584-14.620; P<0.001). In this study, the modified WFNS, WFNS, and H&H scales all had good discriminatory abilities for the prognosis of patients with aSAH. Because of the better effect size in predicting poor outcomes, the modified WFNS scale seems preferable to the WFNS and H&H scales.

The under-representation of several ethnic groups in existing genetic databases and studies have undermined our understanding of the genetic variations and associated traits or diseases in many populations. Cost and technology limitations remain the challenges in performing large-scale genome sequencing projects in many developing countries, including Vietnam. As one of the most rapidly adopted genetic tests, non-invasive prenatal testing (NIPT) data offers an alternative untapped resource for genetic studies. Here we performed a large-scale genomic analysis of 2683 pregnant Vietnamese women using their NIPT data and identified a comprehensive set of 8,054,515 single-nucleotide polymorphisms, among which 8.2% were new to the Vietnamese population. Our study also revealed 24,487 disease-associated genetic variants and their allele frequency distribution, especially 5 pathogenic variants for prevalent genetic disorders in Vietnam. We also observed major discrepancies in the allele frequency distribution of disease-associated genetic variants between the Vietnamese and other populations, thus highlighting a need for genome-wide association studies dedicated to the Vietnamese population. The resulted database of Vietnamese genetic variants, their allele frequency distribution, and their associated diseases presents a valuable resource for future genetic studies.

Targeted therapy with tyrosine kinase inhibitors (TKI) provides survival benefits to a majority of patients with non-small cell lung cancer (NSCLC). However, resistance to TKI almost always develops after treatment. Although genetic and epigenetic alterations have each been shown to drive resistance to TKI in cell line models, clinical evidence for their contribution in the acquisition of resistance remains limited. Here, we employed liquid biopsy for simultaneous analysis of genetic and epigenetic changes in 122 Vietnamese NSCLC patients undergoing TKI therapy and displaying acquired resistance. We detected multiple profiles of resistance mutations in 51 patients (41.8%). Of those, genetic alterations in EGFR , particularly EGFR amplification (n = 6), showed pronounced genome instability and genome-wide hypomethylation. Interestingly, the level of hypomethylation was associated with the duration of response to TKI treatment. We also detected hypermethylation in regulatory regions of Homeobox genes which are known to be involved in tumor differentiation. In contrast, such changes were not observed in cases with MET (n = 4) and HER2 (n = 4) amplification. Thus, our study showed that liquid biopsy could provide important insights into the heterogeneity of TKI resistance mechanisms in NSCLC patients, providing essential information for prediction of resistance and selection of subsequent treatment.

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.