Designing nanocomposite hydrogels with oriented nanosheets has emerged as a promising toolkit to achieve preferential performances that go beyond their disordered counterparts. Although current ...fabrication strategies via electric/magnetic force fields have made remarkable achievements, they necessitate special properties of nanosheets and suffer from an inferior orientation degree of nanosheets. Herein, a facile and universal approach is discovered to elaborate MXene‐based nanocomposite hydrogels with highly oriented, heterogeneous architecture by virtue of supergravity to replace conventional force fields. The key to such architecture is to leverage bidirectional, force‐tunable attributes of supergravity containing coupled orthogonal shear and centrifugal force field for steering high‐efficient movement, pre‐orientation, and stacking of MXene nanosheets in the bottom. Such a synergetic effect allows for yielding heterogeneous nanocomposite hydrogels with a high‐orientation MXene‐rich layer (orientation degree, f = 0.83) and a polymer‐rich layer. The authors demonstrate that MXene‐based nanocomposite hydrogels leverage their high‐orientation, heterogeneous architecture to deliver an extraordinary electromagnetic interference shielding effectiveness of 55.2 dB at 12.4 GHz yet using a super‐low MXene of 0.3 wt%, surpassing most hydrogels‐based electromagnetic shielding materials. This versatile supergravity‐steered strategy can be further extended to arbitrary nanosheets including MoS2, GO, and C3N4, offering a paradigm in the development of oriented nanocomposites.
A novel supergravity‐steered approach is designed to manipulate the assembly of arbitrary nanosheets from MXene to MoS2, GO, and C3N4 for fabricating oriented nanocomposite hydrogels with heterogeneous architecture. The resultant MXene‐based nanocomposite hydrogels showcase an extraordinary electromagnetic interference shielding effectiveness (EMI SE) of 55.2 dB yet using a super‐low MXene of 0.3 wt%, surpassing most hydrogels‐based electromagnetic shielding materials.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The spontaneous emulsification for the formation of water-in-oil (W/O) or oil-in-water (O/W) emulsions needs the help of at least one kind of the third component (surfactant or cosolvent) to ...stabilize the oil-water interface. Herein, with the water/CS
2
-soluble polymer poly(
N
,
N
-diethylacrylamide) (PDEAM) as a surfactant, the spontaneous formation of water-in-PDEAM/CS
2
emulsions is reported for the first time. The strong affinity between PDEAM and water or the increase of PDEAM concentration will accelerate the emulsification process with high dispersed phase content. It is demonstrated that the spontaneous emulsification of condensed water droplets into the PDEAM/CS
2
solution occurs during the breath figure process, resulting in porous films with two levels of pore sizes (
i.e.
, micron and submicron). The emulsification degree and the amounts of submicron-sized pores increase with PDEAM concentration and solidifying time of the solution. This work brings about incremental interest in spontaneous emulsification that may happen during the breath figure process. The combination of these two simultaneous processes provides us with an option to build hierarchically porous structures with condensed and emulsified water droplets as templates. Such porous membranes may have great potential in fields such as separation, cell culture, and biosensing.
The breath figure process based on a spontaneous emulsification system composed of PDEAM/CS
2
and water generates hierarchical pores templated by micron-sized condensed droplets and submicron-sized emulsified droplets.
GABAergic interneurons play an essential role in modulating cortical networks. The progenitor domains of cortical interneurons are localized in developing ventral forebrain, including the medial ...ganglionic eminence (MGE), caudal ganglionic eminence (CGE), preoptic area (POA), and preoptic hypothalamic border domain (POH). Here, we characterized the expression pattern of Zswim5, an MGE‐enriched gene in the mouse forebrain. At E11.5–E13.5, prominent Zswim5 expression was detected in the subventricular zone (SVZ) of MGE, POA, and POH, but not CGE of ventral telencephalon where progenitors of cortical interneurons resided. At E15.5 and E17.5, Zswim5 expression remained in the MGE/pallidum primordium and ventral germinal zone. Zswim5 mRNA was markedly decreased after birth and was absent in the adult forebrain. Interestingly, the Zswim5 expression pattern resembled the tangential migration pathways of cortical interneurons. Zswim5‐positive cells in the MGE appeared to migrate from the MGE through the SVZ of LGE to overlying neocortex. Indeed, Zswim5 was co‐localized with Nkx2.1 and Lhx6, markers of progenitors and migratory cortical interneurons. Double labeling showed that Ascl1/Mash1‐positive cells co‐expressed Zswim5. Zswim5 expressing cells contained none or at most low levels of Ki67 but co‐expressed Tuj1 in the SVZ of MGE. These results suggest that Zswim5 is immediately upregulated as progenitors exiting cell cycle become postmitotic. Given that recent studies have elucidated that the cell fate of cortical interneurons is determined shortly after becoming postmitotic, the timing of Zswim5 expression in early postmitotic interneurons suggests a potential role of Zswim5 in regulation of neurogenesis and tangential migration of cortical interneurons.
We investigated the expression pattern of Zswim5, an MGE‐enriched gene in the mouse forebrain. Zswim5 was expressed in differentiating progenitors of cortical GABAergic interneurons that were undergoing tangential migration, suggesting potential regulation of the development of cortical interneurons by Zswim5.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Polyamines are organic polycations essential for cell growth and differentiation; their aberrant accumulation is often associated with diseases, including many types of cancer. To maintain polyamine ...homeostasis, the catalytic activity and protein abundance of ornithine decarboxylase (ODC), the committed enzyme for polyamine biosynthesis, are reciprocally controlled by the regulatory proteins antizyme isoform 1 (Az₁) and antizyme inhibitor (AzIN). Az₁ suppresses polyamine production by inhibiting the assembly of the functional ODC homodimer and, most uniquely, by targeting ODC for ubiquitin-independent proteolytic destruction by the 26S proteasome. In contrast, AzIN positively regulates polyamine levels by competing with ODC for Az₁ binding. The structural basis of the Az₁-mediated regulation of polyamine homeostasis has remained elusive. Here we report crystal structures of human Az₁ complexed with either ODC or AzIN. Structural analysis revealed that Az₁ sterically blocks ODC homodimerization. Moreover, Az₁ binding triggers ODC degradation by inducing the exposure of a cryptic proteasome-interacting surface of ODC, which illustrates how a substrate protein may be primed upon association with Az₁ for ubiquitin-independent proteasome recognition. Dynamic and functional analyses further indicated that the Az₁-induced binding and degradation of ODC by proteasome can be decoupled, with the intrinsically disordered C-terminal tail fragment of ODC being required only for degradation but not binding. Finally, the AzIN–Az₁ structure suggests how AzIN may effectively compete with ODC for Az₁ to restore polyamine production. Taken together, our findings offer structural insights into the Az-mediated regulation of polyamine homeostasis and proteasomal degradation.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Background
Previously, we used ultrasound (US)‐mediated cisplatin (CDDP)‐loaded microbubbles (CDDP‐MBs) to increase intratumoral CDDP level while decreasing systemic cytotoxicity. Statins have shown ...antitumorigenic properties. Our study investigated the effects of atorvastatin with CDDP‐MBs and US on head neck cancer.
Methods
Cell viability analysis with CDDP‐MBs and atorvastatin combined with US in FaDu cell line were tested. Cell proliferation and glutathione level were also evaluated.
Results
Both CDDP and atorvastatin reduced cell's viability. Coadministration of CDDP and atorvastatin resulted in synergistic inhibitory effect. After US sonication, cell viability with atorvastatin and CDDP was significantly reduced for CDDP combined with MBs (65.98% to 49.13%) and for CDDP‐MBs (86.17% to 50.15%). CDDP‐MBs combined with atorvastatin and US inhibited the proliferation of cells: 19.61% for CDDP‐MBs + atorvastatin + US, 36.28% for CDDP + atorvastatin, and 71.73% for atorvastatin alone. Also, CDDP‐MBs + atorvastatin + US induced apoptosis by decreasing cellular level of glutathione.
Conclusions
Atorvastatin combined with MB‐conjugated CDDP exerts synergistic inhibitory effect on head neck cancer.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
Background
Metformin use in pregnancy is controversial because metformin crosses the placenta and the safety on the fetus has not been well-established. This retrospective study aimed to ...compare pregnancy outcomes in women with preexisting type 2 diabetes receiving metformin or standard insulin treatment.
Methods
The cohort of this population-based study includes women of age 20–44 years with preexisting type 2 diabetes and singleton pregnancies in Taiwan between 2003 and 2014. Subjects were classified into three mutually exclusive groups according to glucose-lowering treatments received before and after becoming pregnant: insulin group, switching group (metformin to insulin), and metformin group. A generalized estimating equation model adjusted for patient age, duration of type 2 diabetes, hypertension, hyperlipidemia, retinopathy, and aspirin use was used to estimate the adjusted odds ratio (aOR) and 95% confidence interval (CI) of adverse pregnancy outcomes.
Results
A total of 1166 pregnancies were identified in the insulin group (
n
= 222), the switching group (
n
= 318) and the metformin group (
n
= 626). The insulin group and the switching group had similar pregnancy outcomes for both the mother and fetus, including risk of primary cesarean section, pregnancy-related hypertension, preeclampsia, preterm birth (< 37 weeks), very preterm birth (< 32 weeks), low birth weight (< 2500 g), high birth weight (> 4000 g), large for gestational age, and congenital malformations. The metformin group had a lower risk of primary cesarean section (aOR = 0.57; 95% CI, 0.40–0.82) and congenital malformations (aOR, 0.51; 95% CI; 0.27–0.94) and similar risk for the other outcomes as compared with the insulin group.
Conclusions
Metformin therapy was not associated with increased adverse pregnancy outcomes in women with type 2 diabetes as compared with standard insulin therapy.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Hyperuricemia has been associated with chronic kidney disease (CKD) progression. The antihyperuricemic febuxostat's potential renoprotective effect has been demonstrated in stage 1–3 CKD. Large‐scale ...studies comparing the renoprotective potential of febuxostat and allopurinol in advanced CKD are lacking. We exclusively selected 6,057 eligible patients with predialysis stage 5 CKD prescribed either febuxostat or allopurinol using the National Health Insurance Research Database in Taiwan during 2012–2015. There were 69.57% of allopurinol users and 42.01% febuxostat users who required long‐term dialysis (P < 0.0001). The adjusted hazard ratio (HR) of 0.65 (95% confidence interval (CI) 0.60–0.70) indicated near 35% lower hazards of long‐term dialysis with febuxostat use. The renal benefit of febuxostat was consistent across most patient subgroups and/or using the propensity score‐matched cohort. The adjusted HR was 0.66 (95% CI, 0.61–0.70) for long‐term dialysis or death. In conclusion, lower risk of progression to dialysis was observed in predialysis stage 5 CKD febuxostat users without compromising survival.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
1-Nitro-pyrene has been considered a compound specific to diesel combustion emission, while 1- and 2-nitro-napthalene are mainly produced through photochemical conversion of naphthalene released to ...the atmosphere. Metabolites of these compounds may serve as biomarkers of exposure to traffic related pollutants. We collected urine samples from 111 healthy and non-smoking subjects within (i.e., during the Beijing Olympics) and outside (i.e., before and after the Olympics) a traffic control regime to improve Beijing's air quality. Urines were analyzed for the sum of 1&2-amino-naphthalene (metabolites of 1- and 2-nitro-naphthalene) and 1-amino-pyrene (a metabolite of 1-nitro-pyrene), using an HPLC-fluorescence method. Within the same time periods, PM2.5 mass and constituents were measured, including elemental carbon, sulfate, nitrate, PAHs, carbon monoxide, nitrogen dioxide, sulfur dioxide, ozone, and particle number concentrations. The associations between the urinary metabolites and air pollutants were analyzed using linear mixed-effects models. From the pre- to during-Olympic period, 1&2-amino-naphthalene and 1-hydroxy-pyrene decreased by 23% (p=0.066) and 16% (p=0.049), respectively, while there was no change in 1-amino-pyrene (2% increase, p=0.892). From during- to post-Olympic period, 1&2-amino-naphthalene, 1-amino-pyrene and 1-hydroxy-pyrene concentrations increased by 26% (p=0.441), 37% (p=0.355), and 3% (p=0.868), respectively. Furthermore, 1&2-amino-naphthalene and 1-hydroxy-pyrene were associated with traffic related pollutants in a similar lag pattern. 1-amino-pyrene was associated more strongly with diesel combustion products (e.g. PN and elemental carbon) and not affected by season. Time-lag analyses indicate strongest/largest associations occurred 24–72h following exposure. 1&2-amino-naphthalene and 1-hydroxy-pyrene can be used as a biomarker of exposure to general vehicle-emitted pollutants. More data are needed to confirm 1-amino-pyrene as a biomarker of exposure to diesel combustion emissions. Controlling creatinine as an independent variable in the models will provide a moderate adjusting effect on the biomarker analysis.
•Urinary polycyclic aromatic hydrocarbon metabolites were analyzed as exposure markers.•Associations were found between polycyclic aromatic hydrocarbon metabolites and general traffic emissions.•More data are needed for associations between 1-amino-pyrene and diesel exhaust particles.•Adjustment for creatinine is essential in urinary biomarker analyses.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Schizophrenia is a devastating neuropsychiatric disease with a globally 1% life-long prevalence. Clinical studies have linked
Zswim6
mutations to developmental and neurological diseases, including ...schizophrenia.
Zswim6
’s function remains largely unknown. Given the involvement of
Zswim6
in schizophrenia and schizophrenia as a neurodevelopmental disease, it is important to understand the spatiotemporal expression pattern of
Zswim6
in the developing brain. Here, we performed a comprehensive analysis of the spatiotemporal expression pattern of
Zswim6
in the mouse forebrain by
in situ
hybridization with radioactive and non-radioactive-labeled riboprobes.
Zswim6
mRNA was detected as early as E11.5 in the ventral forebrain. At E11.5–E13.5,
Zswim6
was highly expressed in the lateral ganglionic eminence (LGE). The LGE consisted of two progenitor populations. Dlx
+
;Er81
+
cells in dorsal LGE comprised progenitors of olfactory bulb interneurons, whereas Dlx
+
;Isl1
+
progenitors in ventral LGE gave rise to striatal projection neurons.
Zswim6
was not colocalized with Er81 in the dorsal LGE. In the ventral LGE,
Zswim6
was colocalized with striatal progenitor marker
Nolz-1
.
Zswim6
was highly expressed in the subventricular zone (SVZ) of LGE in which progenitors undergo the transition from proliferation to differentiation. Double labeling showed that
Zswim6
was not colocalized with proliferation marker Ki67 but was colocalized with differentiation marker Tuj1 in the SVZ, suggesting
Zswim6
expression in early differentiating neurons.
Zswim6
was also expressed in the adjacent structures of medial and caudal ganglionic eminences (MGE, CGE) that contained progenitors of cortical interneurons. At E15.5 and E17.5,
Zswim6
was expressed in several key brain regions that were involved in the pathogenesis of schizophrenia, including the striatum, cerebral cortex, hippocampus, and medial habenular nucleus.
Zswim6
was persistently expressed in the postnatal brain. Cell type analysis indicated that
Zswim6
mRNA was colocalized with
D1R
-expressing striatonigral and
D2R
-expressing striatopallidal neurons of the adult striatum with a higher colocalization in striatopallidal neurons. These findings are of particular interest as striatal dopamine D2 receptors are known to be involved in the pathophysiology of schizophrenia. In summary, the comprehensive analysis provides an anatomical framework for the study of
Zswim6 function and Zswim6-associated neurological disorders
.
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