Self Pre-training with Topology- and Spatiality-aware Masked Autoencoders for 3D Medical Image Segmentation

Masked Autoencoders (MAEs) have been shown to be effective in pre-training Vision Transformers (ViTs) for natural and medical image analysis problems. By reconstructing missing pixel/voxel information in visible patches, a ViT encoder can aggregate contextual information for downstream tasks. But, existing MAE pre-training methods, which were specifically developed with the ViT architecture, lack the ability to capture geometric shape and spatial information, which is critical for medical image segmentation tasks. In this paper, we propose a novel extension of known MAEs for self pre-training (i.e., models pre-trained on the same target dataset) for 3D medical image segmentation. (1) We propose a new topological loss to preserve geometric shape information by computing topological signatures of both the input and reconstructed volumes, learning geometric shape information. (2) We introduce a pre-text task that predicts the positions of the centers and eight corners of 3D crops, enabling the MAE to aggregate spatial information. (3) We extend the MAE pre-training strategy to a hybrid state-of-the-art (SOTA) medical image segmentation architecture and co-pretrain it alongside the ViT. (4) We develop a fine-tuned model for downstream segmentation tasks by complementing the pre-trained ViT encoder with our pre-trained SOTA model. Extensive experiments on five public 3D segmentation datasets show the effectiveness of our new approach

Inducible and Selective Erasure of Memories in the Mouse Brain via Chemical-Genetic Manipulation

SummaryRapid and selective erasures of certain types of memories in the brain would be desirable under certain clinical circumstances. By employing an inducible and reversible chemical-genetic technique, we find that transient αCaMKII overexpression at the time of recall impairs the retrieval of both newly formed one-hour object recognition memory and fear memories, as well as 1-month-old fear memories. Systematic analyses suggest that excessive αCaMKII activity-induced recall deficits are not caused by disrupting the retrieval access to the stored information but are, rather, due to the active erasure of the stored memories. Further experiments show that the recall-induced erasure of fear memories is highly restricted to the memory being retrieved while leaving other memories intact. Therefore, our study reveals a molecular genetic paradigm through which a given memory, such as new or old fear memory, can be rapidly and specifically erased in a controlled and inducible manner in the brain

Forebrain overexpression of CaMKII abolishes cingulate long term depression and reduces mechanical allodynia and thermal hyperalgesia

Activity-dependent synaptic plasticity is known to be important in learning and memory, persistent pain and drug addiction. Glutamate NMDA receptor activation stimulates several protein kinases, which then trigger biochemical cascades that lead to modifications in synaptic efficacy. Genetic and pharmacological techniques have been used to show a role for Ca(2+)/calmodulin-dependent kinase II (CaMKII) in synaptic plasticity and memory formation. However, it is not known if increasing CaMKII activity in forebrain areas affects behavioral responses to tissue injury. Using genetic and pharmacological techniques, we were able to temporally and spatially restrict the over expression of CaMKII in forebrain areas. Here we show that genetic overexpression of CaMKII in the mouse forebrain selectively inhibits tissue injury-induced behavioral sensitization, including allodynia and hyperalgesia, while behavioral responses to acute noxious stimuli remain intact. CaMKII overexpression also inhibited synaptic depression induced by a prolonged repetitive stimulation in the ACC, suggesting an important role for CaMKII in the regulation of cingulate neurons. Our results suggest that neuronal CaMKII activity in the forebrain plays a role in persistent pain

Progress and applications of (Cu–)Ag–Bi–I semiconductors, and their derivatives, as next-generation lead-free materials for photovoltaics, detectors and memristors

The search for efficient but inexpensive photovoltaics over the past decade has been disrupted by the advent of lead-halide perovskite solar cells. Despite impressive rises in performance, the toxicity and stability concerns of these materials have prompted a broad, interdisciplinary community across the world to search for lead-free and stable alternatives. A set of such materials that have recently gained attention are semiconductors in the CuI–AgI–BiI3 phase space and their derivatives. These materials include ternary silver bismuth iodide compounds (AgaBibIa+3b), ternary copper bismuth iodide Cu–Bi–I compounds and quaternary Cu–Ag–Bi–I materials, as well as analogues with Sb substituted into the Bi site and Br into the I site. These compounds are comprised of a cubic close-packed sub-lattice of I, with Ag and Bi occupying octahedral holes, while Cu occupies tetrahedral holes. The octahedral motifs adopted by these compounds are either spinel, CdCl2-type, or NaVO2-type. NaVO2-type AgaBibIa+3b compounds are also known as rudorffites. Many of these compounds have thus far demonstrated improved stability and reduced toxicity compared to halide perovskites, along with stable bandgaps in the 1.6–1.9 eV range, making them highly promising for energy harvesting and detection applications. This review begins by discussing the progress in the development of these semiconductors over the past few years, focusing on their optoelectronic properties and process–property–structure relationships. Next, we discuss the progress in developing Ag–Bi–I and Cu–Bi–I compounds for solar cells, indoor photovoltaics, photodetectors, radiation detectors and memristors. We conclude with a discussion of the critical fundamental questions that need to be addressed to push this area forward, and how the learnings from the wider metal-halide semiconductor field can inform future directions

The zinc finger transcription factor ZKSCAN3 promotes prostate cancer cell migration

In our previous studies, ZKSCAN3 was demonstrated to be over-expressed in invasive colonic tumor cells and their liver metastases, but minimally expressed in adjacent non-transformed tissues. Further preliminary data showed that ZKSCAN3 was expressed in a majority of prostate cancer patient samples, but not in normal prostate tissues. Moreover, the ZKSCAN3 protein is highly expressed in the PC3 prostate cancer cell line, which has high metastatic potential, but little expression was observed in non-metastatic prostate cancer cell lines. Thus, we hypothesized that ZKSCAN3 could participate in tumor metastasis by regulating tumor cell migration. To test this hypothesis, ZKSCAN3 mRNA was knocked down by ZKSCAN3 specific shRNA in PC3 cells and a significant decrease in cell motility was observed. In contrast, when ZKSCAN3 cDNA was overexpressed in PC3 cells, cell detachment was observed and suspension culture induced apoptosis was greatly decreased, suggesting that ZKSCAN3 is able to enhance PC3 cell survival under anoikis stress. Additional wound healing and invasion assays showed that cell migration was enhanced by ZKSCAN3 expression. Interestingly, the ZKSCAN3 gene was amplified in 26% (5/19) of metastatic prostate cancers and 20% (1/5) of lymph node metastases, but there was no amplification found in primary prostate cancers, further supporting the role of ZKSCAN3 in tumor cell migration. In vivo studies using orthotopic tumor models indicated that overexpression of ZKSCAN3 significantly enhanced tumorigenicity. Taken together, we provide evidence that ZKSCAN3, a zinc finger transcription factor, plays a critical role in promoting prostate cancer cell migration

Air-stable bismuth sulfobromide (BiSBr) visible-light absorbers : optoelectronic properties and potential for energy harvesting

ns2 compounds have recently attracted considerable interest due to their potential to replicate the defect tolerance of lead-halide perovskites and overcome their toxicity and stability limitations. However, only a handful of compounds beyond the perovskite family have been explored thus far. Herein, we investigate bismuth sulfobromide (BiSBr), which is a quasi-one-dimensional semiconductor, but very little is known about its optoelectronic properties or how it can be processed as thin films. We develop a solution processing route to achieve phase-pure, stoichiometric BiSBr films (ca. 240 nm thick), which we show to be stable in ambient air for over two weeks without encapsulation. The bandgap (1.91 ± 0.06 eV) is ideal for harvesting visible light from common indoor light sources, and we calculate the optical limit in efficiency (i.e., spectroscopic limited maximum efficiency, SLME) to be 43.6% under 1000 lux white light emitting diode illumination. The photoluminescence lifetime is also found to exceed the 1 ns threshold for photovoltaic absorber materials worth further development. Through X-ray photoemission spectroscopy and Kelvin probe measurements, we find the BiSBr films grown to be n-type, with an electron affinity of 4.1 ± 0.1 eV and ionization potential of 6.0 ± 0.1 eV, which are compatible with a wide range of established charge transport layer materials. This work shows BiSBr to hold promise for indoor photovoltaics, as well as other visible-light harvesting applications, such as photoelectrochemical cells, or top-cells for tandem photovoltaics

Grain engineering of Sb2S3 thin films to enable efficient planar solar cells with high open-circuit voltage

Sb2S3 is a promising environmentally friendly semiconductor for high performance solar cells. But, like many other polycrystalline materials, Sb2S3 is limited by nonradiative recombination and carrier scattering by grain boundaries (GBs). This work shows how the GB density in Sb2S3 films can be significantly reduced from 1068 ± 40 to 327 ± 23 nm µm−2 by incorporating an appropriate amount of Ce3+ into the precursor solution for Sb2S3 deposition. Through extensive characterization of structural, morphological, and optoelectronic properties, complemented with computations, it is revealed that a critical factor is the formation of an ultrathin Ce2S3 layer at the CdS/Sb2S3 interface, which can reduce the interfacial energy and increase the adhesion work between Sb2S3 and the substrate to encourage heterogeneous nucleation of Sb2S3, as well as promote lateral grain growth. Through reductions in nonradiative recombination at GBs and/or the CdS/Sb2S3 heterointerface, as well as improved charge-carrier transport properties at the heterojunction, this work achieves high performance Sb2S3 solar cells with a power conversion efficiency reaching 7.66%. An impressive open-circuit voltage (VOC) of 796 mV is achieved, which is the highest reported thus far for Sb2S3 solar cells. This work provides a strategy to simultaneously regulate the nucleation and growth of Sb2S3 absorber films for enhanced device performance

Anti-HIV-1 Activity of a New Scorpion Venom Peptide Derivative Kn2-7

For over 30 years, HIV/AIDS has wreaked havoc in the world. In the absence of an effective vaccine for HIV, development of new anti-HIV agents is urgently needed. We previously identified the antiviral activities of the scorpion-venom-peptide-derived mucroporin-M1 for three RNA viruses (measles viruses, SARS-CoV, and H5N1). In this investigation, a panel of scorpion venom peptides and their derivatives were designed and chosen for assessment of their anti-HIV activities. A new scorpion venom peptide derivative Kn2-7 was identified as the most potent anti-HIV-1 peptide by screening assays with an EC50 value of 2.76 µg/ml (1.65 µM) and showed low cytotoxicity to host cells with a selective index (SI) of 13.93. Kn2-7 could inhibit all members of a standard reference panel of HIV-1 subtype B pseudotyped virus (PV) with CCR5-tropic and CXCR4-tropic NL4-3 PV strain. Furthermore, it also inhibited a CXCR4-tropic replication-competent strain of HIV-1 subtype B virus. Binding assay of Kn2-7 to HIV-1 PV by Octet Red system suggested the anti-HIV-1 activity was correlated with a direct interaction between Kn2-7 and HIV-1 envelope. These results demonstrated that peptide Kn2-7 could inhibit HIV-1 by direct interaction with viral particle and may become a promising candidate compound for further development of microbicide against HIV-1

Isofagomine In Vivo Effects in a Neuronopathic Gaucher Disease Mouse

The pharmacological chaperone, isofagomine (IFG), enhances acid β-glucosidase (GCase) function by altering folding, trafficking, and activity in wild-type and Gaucher disease fibroblasts. The in vivo effects of IFG on GCase activity, its substrate levels, and phenotype were evaluated using a neuronopathic Gaucher disease mouse model, 4L;C* (V394L/V394L + saposin C-/-) that has CNS accumulation of glucosylceramide (GC) and glucosylsphingosine (GS) as well as progressive neurological deterioration. IFG administration to 4L;C* mice at 20 or 600 mg/kg/day resulted in life span extensions of 10 or 20 days, respectively, and increases in GCase activity and protein levels in the brain and visceral tissues. Cerebral cortical GC and GS levels showed no significant reductions with IFG treatment. Increases of GC or GS levels were detected in the visceral tissues of IFG treated (600 mg/kg/day) mice. The attenuations of brain proinflammatory responses in the treated mice were evidenced by reductions in astrogliosis and microglial cell activation, and decreased p38 phosphorylation and TNFα levels. Terminally, axonal degeneration was present in the brain and spinal cord from untreated and treated 4L;C* mice. These data demonstrate that IFG exerts in vivo effects by enhancing V394L GCase protein and activity levels, and in mediating suppression of proinflammation, which led to delayed onset of neurological disease and extension of the life span of 4L;C* mice. However, this was not correlated with a reduction in the accumulation of lipid substrates

Long-Term Exposure to Ambient Air Pollution and Mortality Due to Cardiovascular Disease and Cerebrovascular Disease in Shenyang, China

BACKGROUND: The relationship between ambient air pollution exposure and mortality of cardiovascular and cerebrovascular diseases in human is controversial, and there is little information about how exposures to ambient air pollution contribution to the mortality of cardiovascular and cerebrovascular diseases among Chinese. The aim of the present study was to examine whether exposure to ambient-air pollution increases the risk for cardiovascular and cerebrovascular disease. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a retrospective cohort study among humans to examine the association between compound-air pollutants [particulate matter <10 µm in aerodynamic diameter (PM(10)), sulfur dioxide (SO(2)) and nitrogen dioxide (NO(2))] and mortality in Shenyang, China, using 12 years of data (1998-2009). Also, stratified analysis by sex, age, education, and income was conducted for cardiovascular and cerebrovascular mortality. The results showed that an increase of 10 µg/m(3) in a year average concentration of PM(10) corresponds to 55% increase in the risk of a death cardiovascular disease (hazard ratio [HR], 1.55; 95% confidence interval [CI], 1.51 to 1.60) and 49% increase in cerebrovascular disease (HR, 1.49; 95% CI, 1.45 to 1.53), respectively. The corresponding figures of adjusted HR (95%CI) for a 10 µg/m(3) increase in NO(2) was 2.46 (2.31 to 2.63) for cardiovascular mortality and 2.44 (2.27 to 2.62) for cerebrovascular mortality, respectively. The effects of air pollution were more evident in female that in male, and nonsmokers and residents with BMI<18.5 were more vulnerable to outdoor air pollution. CONCLUSION/SIGNIFICANCE: Long-term exposure to ambient air pollution is associated with the death of cardiovascular and cerebrovascular diseases among Chinese populations