The development of kesterite Cu2ZnSn(S,Se)4 thin‐film solar cells is currently hindered by the large deficit of open‐circuit voltage (Voc), which results from the easy formation of CuZn antisite ...acceptor defects. Suppressing the formation of CuZn defects, especially near the absorber/buffer interface, is thus critical for the further improvement of kesterite solar cells. In this paper, it is shown that there is a large disparity between the defects in Cu‐ and Ag‐based kesterite semiconductors, i.e., the CuZn or CuCd acceptor defects have high concentration and are the dominant defects in Cu2ZnSn(S,Se)4 or Cu2CdSnS4, but the AgZn acceptor has only a low concentration and the dominant defects are donors in Ag2ZnSnS4. Therefore, the Cu‐based kesterites always show p‐type conductivity, while the Ag‐based kesterites show either intrinsic or weak n‐type conductivity. Based on this defect disparity and calculated band alignment, it is proposed that the Voc limit of the kesterite solar cells can be overcome by alloying Cu2ZnSn(S,Se)4 with Ag2ZnSn(S,Se)4, and the composition‐graded (Cu,Ag)2ZnSn(S,Se)4 alloys should be ideal light‐absorber materials for achieving higher efficiency kesterite solar cells.
A new strategy is proposed to overcome the Voc bottleneck and increase the efficiency of the kesterite solar cells. This is achieved by forming composition‐graded (Cu1–xAgx)2ZnSn(S,Se)4 alloys as the absorber layer.
The amyloid cascade hypothesis has been dominating drug discovery for Alzheimer's disease (AD) for the last two decades. The failure of the development of effective drugs for slowing down or ...reversing the progression of AD warrants the AD field to consider out-of-the-box thinking and therapeutic approaches. We propose the multifactorial hypothesis of AD, emphasizing that AD is caused by multiple etiological factors, which may result in common brain pathology and functional consequences through several separate but integrated molecular pathways. More than one etiological factor and mechanistic pathway may be involved in a single individual with sporadic AD, and different individuals may have different etiological factors, involving different mechanisms/pathways. We urge the recognition of the multifactorial nature of AD and the paradigm shift of AD drug development from a single target to multiple targets, either with the multitarget-directed ligands approach or the cocktail therapy approach. We believe that patient stratification and the use of the precision medicine model will also benefit AD drug discovery.
The kesterite‐structured semiconductors Cu2ZnSnS4 and Cu2ZnSnSe4 are drawing considerable attention recently as the active layers in earth‐abundant low‐cost thin‐film solar cells. The additional ...number of elements in these quaternary compounds, relative to binary and ternary semiconductors, results in increased flexibility in the material properties. Conversely, a large variety of intrinsic lattice defects can also be formed, which have important influence on their optical and electrical properties, and hence their photovoltaic performance. Experimental identification of these defects is currently limited due to poor sample quality. Here recent theoretical research on defect formation and ionization in kesterite materials is reviewed based on new systematic calculations, and compared with the better studied chalcopyrite materials CuGaSe2 and CuInSe2. Four features are revealed and highlighted: (i) the strong phase‐competition between the kesterites and the coexisting secondary compounds; (ii) the intrinsic p‐type conductivity determined by the high population of acceptor CuZn antisites and Cu vacancies, and their dependence on the Cu/(Zn+Sn) and Zn/Sn ratio; (iii) the role of charge‐compensated defect clusters such as 2CuZn+SnZn, VCu+ZnCu and ZnSn+2ZnCu and their contribution to non‐stoichiometry; (iv) the electron‐trapping effect of the abundant 2CuZn+SnZn clusters, especially in Cu2ZnSnS4. The calculated properties explain the experimental observation that Cu poor and Zn rich conditions (Cu/(Zn+Sn) ≈ 0.8 and Zn/Sn ≈ 1.2) result in the highest solar cell efficiency, as well as suggesting an efficiency limitation in Cu2ZnSn(S,Se)4 cells when the S composition is high.
The physics of lattice defects in kesterite structured Cu2ZnSnS4 and Cu2ZnSnSe4 and chalcopyrite structured CuInSe2 and CuGaSe2 crystals is investigated and compared based on the first‐principles calculations. The influence of shallow acceptor defects, deep donor defects and charge‐compensated defect clusters on the non‐stoichiometry, hole carrier concentration and solar cell efficiency of these materials is revealed.
The Hedgehog (Hh) pathway involved in development and regeneration is activated by the extracellular binding of Hh to the membrane receptor Patched (Ptch). We report the cryo-EM structures of human ...Ptch1 alone and in complex with the N-terminal domain of human Sonic hedgehog (ShhN) at resolutions of 3.9 Å and 3.6 Å, respectively. Ptch1 comprises two interacting extracellular domains ECD1 and ECD2 and twelve transmembrane segments (TMs), with TMs 2-6 constituting the sterol-sensing domain (SSD). Two steroid-shaped densities are resolved in both structures, one enclosed by ECD1/2, and the other on the membrane-facing cavity of SSD. Structure-guided mutational analysis shows that interaction between ShhN and Ptch1 is steroid-dependent. The structure of a steroid binding-deficient Ptch1 mutant displays pronounced conformational rearrangements.
It was believed that the Se‐rich synthesis condition can suppress the formation of deep‐level donor defect VSe (selenium vacancy) in Sb2Se3 and is thus critical for fabricating high‐efficiency Sb2Se3 ...solar cells. However, here it is shown that by first‐principles calculations the density of VSe increases unexpectedly to 1016 cm−3 when the Se chemical potential increases, so Se‐rich condition promotes rather than suppresses the formation of VSe. Therefore, high density of VSe is thermodynamically inevitable, no matter under Se‐poor or Se‐rich conditions. This abnormal behavior can be explained by a physical concept “defect‐correlation”, i.e., when donor and acceptor defects compensate each other, all defects become correlated with each other due to the formation energy dependence on Fermi level which is determined by densities of all ionized defects. In quasi‐1D Sb2Se3, there are many defects and the complicated defect‐correlation can give rise to abnormal behaviors, e.g., lowering Fermi level and thus decreasing the formation energy of ionized donor VSe2+ in Se‐rich Sb2Se3. Such behavior exists also in Sb2S3. It explains the recent experiments that the extremely Se‐rich condition causes the efficiency drop of Sb2Se3 solar cells, and demonstrates that the common chemical intuition and defect engineering strategies may be invalid in compensated semiconductors.
First‐principles calculations show that the Se‐rich synthesis condition promotes rather than suppresses the formation of selenium vacancy defects in Sb2Se3. To explain such an abnormal behavior, a new physical concept, the defect‐correlation effect, which can be general in compound semiconductors with donor‐acceptor compensation and leads to abnormal defect behavior in Sb2Se3, Sb2S3 and other low‐symmetry or multinary semiconductors, is introduced.
ABCA1, an ATP-binding cassette (ABC) subfamily A exporter, mediates the cellular efflux of phospholipids and cholesterol to the extracellular acceptor apolipoprotein A-I (apoA-I) for generation of ...nascent high-density lipoprotein (HDL). Mutations of human ABCA1 are associated with Tangier disease and familial HDL deficiency. Here, we report the cryo-EM structure of human ABCA1 with nominal resolutions of 4.1 Å for the overall structure and 3.9 Å for the massive extracellular domain. The nucleotide-binding domains (NBDs) display a nucleotide-free state, while the two transmembrane domains (TMDs) contact each other through a narrow interface in the intracellular leaflet of the membrane. In addition to TMDs and NBDs, two extracellular domains of ABCA1 enclose an elongated hydrophobic tunnel. Structural mapping of dozens of disease-related mutations allows potential interpretation of their diverse pathogenic mechanisms. Structural-based analysis suggests a plausible “lateral access” mechanism for ABCA1-mediated lipid export that may be distinct from the conventional alternating-access paradigm.
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•Cryo-EM structure of human ABCA1 at 4.1 Å resolution•An “outward-facing” conformation of TMD in the nucleotide-free state•An elongated hydrophobic tunnel within the massive extracellular domains•Structural mapping allows mechanistic interpretation of disease mutations
The human ABCA1 transporter moves lipids from within the membrane through a narrow gate to support HDL biosynthesis.
Abstract O-GlcNAcylation is the posttranslational modification of intracellular proteins by O-linked β-N-acetylglucosamine (O-GlcNAc). The discovery of O-GlcNAc modification of tau and its impact on ...tau phosphorylation has attracted recent research interest in O-GlcNAc studies in the Alzheimer's disease (AD) field. Modification of proteins by O-GlcNAc occurs extensively in the brain. The expressions and activities of the enzymes catalyzing O-GlcNAc cycling are several-fold higher in the brain than in the peripheral tissues. The O-GlcNAcylation levels of brain proteins including tau are decreased in AD brain, probably due to decreased brain glucose metabolism. The reduction of brain O-GlcNAcylation appears to mediate the molecular mechanism by which decreased brain glucose metabolism contributes to neurodegeneration. Studies on mouse models of tauopathies suggest a neuroprotective role of pharmacological elevation of brain O-GlcNAc, which could potentially be a promising approach for treating AD and other neurodegenerative diseases.
Human serine palmitoyltransferase (SPT) complex catalyzes the initial and rate-limiting step in the de novo biosynthesis of all sphingolipids. ORMDLs regulate SPT function, with human ORMDL3 being ...related to asthma. Here we report three high-resolution cryo-EM structures: the human SPT complex, composed of SPTLC1, SPTLC2 and SPTssa; the SPT-ORMDL3 complex; and the SPT-ORMDL3 complex bound to two substrates, PLP-L-serine (PLS) and a non-reactive palmitoyl-CoA analogue. SPTLC1 and SPTLC2 form a dimer of heterodimers as the catalytic core. SPTssa participates in acyl-CoA coordination, thereby stimulating the SPT activity and regulating the substrate selectivity. ORMDL3 is located in the center of the complex, serving to stabilize the SPT assembly. Our structural and biochemical analyses provide a molecular basis for the assembly and substrate selectivity of the SPT and SPT-ORMDL3 complexes, and lay a foundation for mechanistic understanding of sphingolipid homeostasis and for related therapeutic drug development.
Highlights
A facile one‐step hydrothermal method for producing gram‐scale 1T@2H-MoS
2
by imbedding the guest molecules and ions was developed.
The influence of different MoS
2
phase for ...electromagnetic absorbing properties was explored by analyzing electromagnetic parameters of 1T/2H MoS
2
and 2H MoS
2
with 50%, 40%, 30%, 20%, 15%, and 10% filler loading.
Taking the advantage of 1T/2H MoS
2
, the flexible CF@1T/2H MoS
2
was also synthesized to mind the request of flexible portable microwave absorption electronic devices.
Phase engineering is an important strategy to modulate the electronic structure of molybdenum disulfide (MoS
2
). MoS
2
-based composites are usually used for the electromagnetic wave (EMW) absorber, but the effect of different phases on the EMW absorbing performance, such as 1T and 2H phase, is still not studied. In this work, micro-1T/2H MoS
2
is achieved via a facile one-step hydrothermal route, in which the 1T phase is induced by the intercalation of guest molecules and ions. The EMW absorption mechanism of single MoS
2
is revealed by presenting a comparative study between 1T/2H MoS
2
and 2H MoS
2
. As a result, 1T/2H MoS
2
with the matrix loading of 15% exhibits excellent microwave absorption property than 2H MoS
2
. Furthermore, taking the advantage of 1T/2H MoS
2
, a flexible EMW absorbers that ultrathin 1T/2H MoS
2
grown on the carbon fiber also performs outstanding performance only with the matrix loading of 5%. This work offers necessary reference to improve microwave absorption performance by phase engineering and design a new type of flexible electromagnetic wave absorption material to apply for the portable microwave absorption electronic devices.
Moderate dietary restriction can ameliorate age‐related chronic diseases such as Alzheimer's disease (AD) by increasing the expression of neurotrophic factors and promoting neurogenesis in the brain. ...Glycogen synthase kinase‐3β (GSK‐3β) signaling is essential for the coordination of progenitor cell proliferation and differentiation during brain development. The mechanisms by which GSK‐3β is involved in dietary restriction‐induced neurogenesis and cognitive improvement remain unclear. Six‐month‐old male 3xTg‐AD and wild‐type mice were fed on alternate days (intermittent fasting, IF) or ad libitum (AL) for 3 months. GSK‐3β activity was regulated by bilaterally infusing lentiviral vectors carrying siRNA targeting GSK‐3β into the dentate gyrus region of the hippocampus. Intermittent fasting promoted neuronal differentiation and maturation in the dentate gyrus and ameliorated recognized dysfunction in 3xTg‐AD mice. These effects were reversed by siRNA targeting GSK‐3β. After intermittent fasting, the insulin and protein kinase A signaling pathways were inhibited, while the adenosine monophosphate‐activated protein kinase and brain‐derived neurotrophic factor pathways were activated. These findings suggest that intermittent fasting can promote neuronal differentiation and maturation in the hippocampus by activating GSK‐3β, thus improving learning and memory.
Moderate dietary restriction can ameliorate age‐related chronic diseases such as Alzheimer's disease (AD) by increasing the expression of neurotrophic factors and promoting neurogenesis in the brain. In this study, after three months of intermittent fasting ofix‐month‐old male 3xTg‐AD mice, cAMP/PKA was downregulated, and blood glucose and insulin levels were reduced, then insulin/PI3K/Akt pathway were inhibited, which consequently increased the activity of GSK‐3β. Meanwhile, AMPK was activated and BDNF level was increased. Therefore, activated GSK‐3β and increased BDNF promoted the differentiation and survival of newborn neurons, which improved cognitive impairment in Alzheimer's disease.
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