Since 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002, MERS-CoV in 2012, and the newly emerged SARS-CoV-2 in late 2019. However, little is currently known about the biology of SARS-CoV-2. Here, using SARS-CoV-2 S protein pseudovirus system, we confirm that human angiotensin converting enzyme 2 (hACE2) is the receptor for SARS-CoV-2, find that SARS-CoV-2 enters 293/hACE2 cells mainly through endocytosis, that PIKfyve, TPC2, and cathepsin L are critical for entry, and that SARS-CoV-2 S protein is less stable than SARS-CoV S. Polyclonal anti-SARS S1 antibodies T62 inhibit entry of SARS-CoV S but not SARS-CoV-2 S pseudovirions. Further studies using recovered SARS and COVID-19 patients' sera show limited cross-neutralization, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for SARS-CoV-2. 1 1234567890():,;C oronaviruses (CoVs) infect human and animals and cause varieties of diseases, including respiratory, enteric, renal, and neurological diseases 1 . They are classified into four genera, alpha-CoV, beta-CoV, gamma-CoV, and delta-CoV 2 . Since beginning of this century, there have already been three zoonotic outbreaks of beta-CoVs. In 2002-2003, severe acute respiratory syndrome coronavirus (SARS-CoV) 3,4 , a lineage B beta-CoV, emerged from bat and palm civet 5,6 , and infected over 8000 people and caused about 800 deaths 7 . In 2012, Middle East respiratory syndrome coronavirus (MERS-CoV), a lineage C beta-CoV, was discovered as the causative agent of a severe respiratory syndrome in Saudi Arabia 8 , currently with 2494 confirmed cases and 858 deaths 9 , it remains endemic in Middle East, and dromedary camel is considered as the zoonotic reservoir host of MERS-CoV. At the end of 2019, a novel coronavirus, named SARS-CoV-2, was found in patients with severe pneumonia in Wuhan, China 10-12 . Viruses were isolated from patients and sequenced. Phylogenetical analysis revealed that it is a lineage B beta-CoV and closely related to a SARS-like (SL) CoV, RaTG13, discovered in a cave of Yunnan, China, in 2013 13 . They share about 96% nucleotide sequence identities, suggesting that SARS-CoV-2 might have emerged from a Bat SL-CoV. However, the intermediate host or whether there is an intermediate host remains to be determined.CoV uses its spike glycoprotein (S), a main target for neutralization antibody, to bind its receptor, and mediate membrane fusion and virus entry. Each monomer of trimeric S protein is about 180 kDa, and contains two subunits, S1 and S2, mediating attachment and membrane fusion, respectively. In the structure, N-and C-terminal portions of S1 fold as two independent domains, N-terminal domain (NTD) and C-terminal domain (C-domain) (Fig. 1a). Depending on the virus, either NTD or Cdomain can serve as the receptor-binding domain (RBD). While RBD of mouse hepatitis virus (MHV) is located at the NTD 14 , most of other CoVs, including SARS-CoV and MERS-CoV use C-...

During the past decade, inorganic CQDs, namely the lead chalcogenides (e.g., PbS), have attracted tremendous attention in solution-processed solar cells. Due to the great efforts on CQDs synthesis modification, [7][8][9] surface passivation, [10][11][12] and device fabrication optimization, [13][14][15][16] PbS QD solar cells continue to progress at an extraordinary rate, improving overall efficiencies by ≈1% per year and currently have a certified power conversion efficiency (PCE) exceeding 12%. [17] Meanwhile, the past decade has witnessed unprecedented success of organicinorganic hybrid perovskites in PV applications, with the reported PCE of perovskite solar cells exceeding 23%. [18][19][20][21][22][23][24][25][26][27][28] However, the challenging stability issues of these hybrid perovskites further motivate the research of all-inorganic perovskites (CsPbX 3 , X = Cl − , Br − , I − or mixed halides) without any volatile organic components. [29][30][31][32][33][34][35][36][37][38] Among these all-inorganic perovskite materials, α-CsPbI 3 exhibits an ideal optical bandgap (E g ) of 1.73 eV for PV applications. However, the nonphotoactive orthorhombic phase (E g = 2.82 eV) is more thermodynamically preferred at low temperature. [29] Therefore, the perovskite phase of CsPbI 3 usually requires complex annealing processes at high temperature to achieve satisfactory film quality. As mentioned above, QD technology offers colloidal synthesis of conventional bulk materials, which Surface manipulation of quantum dots (QDs) has been extensively reported to be crucial to their performance when applied into optoelectronic devices, especially for photovoltaic devices. In this work, an efficient surface passivation method for emerging CsPbI 3 perovskite QDs using a variety of inorganic cesium salts (cesium acetate (CsAc), cesium idodide (CsI), cesium carbonate (Cs 2 CO 3 ), and cesium nitrate (CsNO 3 )) is reported. The Cs-salts post-treatment can not only fill the vacancy at the CsPbI 3 perovskite surface but also improve electron coupling between CsPbI 3 QDs. As a result, the free carrier lifetime, diffusion length, and mobility of QD film are simultaneously improved, which are beneficial for fabricating high-quality conductive QD films for efficient solar cell devices. After optimizing the post-treatment process, the short-circuit current density and fill factor are significantly enhanced, delivering an impressive efficiency of 14.10% for CsPbI 3 QD solar cells. In addition, the Cs-salt-treated CsPbI 3 QD devices exhibit improved stability against moisture due to the improved surface environment of these QDs. These findings will provide insight into the design of high-performance and low-trap-states perovskite QD films with desirable optoelectronic properties. Perovskite Quantum DotsThe ORCID identification number(s) for the author(s) of this article can be found under https://doi.Solution-processed colloidal quantum dots (CQDs) are promising candidates for the next generation photovoltaics (PVs) due to the excellent tuna...

Emerging all-inorganic perovskite nanocrystals can retain a desired crystal structure under ambient conditions and offer easy solution processability. In this work, we have demonstrated CsPbI 3 perovskite quantum dot (QD) solar cells with a remarkable efficiency approaching 13% and an extremely low energy loss of 0.45 eV by employing a series of dopant-free polymeric hole-transporting materials (HTMs). The CsPbI 3 QD solar cells use polymer HTMs to achieve efficient charge extraction at QD/polymer interfaces and avoid device instability caused by complex doping and oxidation processes required by conventional Spiro-OMeTAD. Meanwhile, the CsPbI 3 QD photovoltaic devices can be fabricated at room temperature and exhibit more reproducible film quality, showing potential advantages over current all-inorganic thin-film perovskite solar cells. We believe that our findings will catalyze the development of new device structures, specifically for perovskite QDs, and help realize the promising potential of all-inorganic perovskite solar cells.

Many neurological disorders are caused by expanded trinucleotide repeats1, including Machado-Joseph Disease (MJD)2 and Huntington Disease (HD)3. MJD and HD are caused by expanded CAG repeats within the ataxin-3 (ATXN3) and huntingtin (HTT) genes. Inhibiting expression of ATXN3 or HTT are promising therapeutic strategies, but indiscriminant inhibition of wild-type and mutant alleles may lead to toxicity. We hypothesized that expanded triplet repeat mRNA might be preferentially recognized by complementary oligomers. We observe selective inhibition of mutant ataxin-3 and HTT protein expression by peptide nucleic acid (PNA) and locked nucleic acid (LNA) oligomers targeting CAG repeats. Duplex RNAs were less selective, suggesting an advantage for single-stranded oligomers. Inhibiting mutant HTT expression protected cultured striatal neurons from an HD mouse model against glutamate-induced toxicity. Antisense oligomers that discriminate between wild-type and mutant genes on the basis of repeat length offer new options for treating MJD, HD, and other hereditary diseases.

SUMMARY Inhibiting expression of huntingtin (HTT) protein is a promising strategy for treating Huntington’s Disease (HD), but indiscriminant inhibition of both wild-type and mutant alleles may lead to toxicity. An ideal silencing agent would block expression of mutant HTT while leaving expression of wild-type HTT intact. We observe that fully complementary duplex RNAs targeting the expanded CAG repeat within HTT mRNA block expression of both alleles. Switching the RNAi mechanism towards that used by miRNAs by introducing one or more mismatched bases into these duplex RNAs leads to potent (< 10 nM) and highly selective (>30-fold relative to wild-type HTT) inhibition of mutant HTT expression in patient derived cells. Potent, allele selective inhibition of HTT by mismatched RNAs provides a new option for developing HD therapeutics.

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Abstract. We consider a metric measure space (M, d, µ) and a heat kernel pt(x, y) on M satisfying certain upper and lower estimates, which depend on two parameters α and β. We show that under additional mild assumptions, these parameters are determined by the intrinsic properties of the space (M, d, µ). Namely, α is the Hausdorff dimension of this space, whereas β, called the walk dimension, is determined via the properties of the family of Besov spaces W σ,2 on M . Moreover, the parameters α and β are related by the inequalities 2 ≤ β ≤ α + 1.We prove also the embedding theorems for the space W β/2,2 , and use them to obtain the existence results for weak solutions to semilinear elliptic equations on M of the formwhere L is the generator of the semigroup associated with pt. The framework in this paper is applicable for a large class of fractal domains, including the generalized Sierpiński carpet in R n .

Advanced data encryption requires the use of true random number generators (TRNGs) to produce unpredictable sequences of bits. TRNG circuits with high degree of randomness and low power consumption may be fabricated by using the random telegraph noise (RTN) current signals produced by polarized metal/insulator/metal (MIM) devices as entropy source. However, the RTN signals produced by MIM devices made of traditional insulators, i.e., transition metal oxides like HfO2 and Al2O3, are not stable enough due to the formation and lateral expansion of defect clusters, resulting in undesired current fluctuations and the disappearance of the RTN effect. Here, the fabrication of highly stable TRNG circuits with low power consumption, high degree of randomness (even for a long string of 224 − 1 bits), and high throughput of 1 Mbit s−1 by using MIM devices made of multilayer hexagonal boron nitride (h‐BN) is shown. Their application is also demonstrated to produce one‐time passwords, which is ideal for the internet‐of‐everything. The superior stability of the h‐BN‐based TRNG is related to the presence of few‐atoms‐wide defects embedded within the layered and crystalline structure of the h‐BN stack, which produces a confinement effect that avoids their lateral expansion and results in stable operation.