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As of December 2022, 2603 laboratory-identified Middle East respiratory syndrome coronavirus (MERS-CoV) infections and 935 associated deaths, with a mortality rate of 36%, had been reported to the World Health Organization (WHO). However, there are still no vaccines for MERS-CoV, which makes the prevention and control of MERS-CoV difficult. In this study, we generated two DNA vaccine candidates by integrating MERS-CoV Spike (S) gene into a replicating Vaccinia Tian Tan (VTT) vector. Compared to homologous immunization with either vaccine, mice immunized with DNA vaccine prime and VTT vaccine boost exhibited much stronger and durable humoral and cellular immune responses. The immunized mice produced robust binding antibodies and broad neutralizing antibodies against the EMC2012, England1 and KNIH strains of MERS-CoV. Prime-Boost immunization also induced strong MERS-S specific T cells responses, with high memory and poly-functional (CD107a-IFN-γ-TNF-α) effector CD8+T cells. In conclusion, the research demonstrated that DNA-Prime/VTT-Boost strategy could elicit robust and balanced humoral and cellular immune responses against MERS-CoV-S. This study not only provides a promising set of MERS-CoV vaccine candidates, but also proposes a heterologous sequential immunization strategy worthy of further development.

Video captioning aims to generate natural language descriptions for a given video clip. Existing methods mainly focus on end-to-end representation learning via word-by-word comparison between predicted captions and ground-truth texts. Although significant progress has been made, such supervised approaches neglect semantic alignment between visual and linguistic entities, which may negatively affect the generated captions. In this work, we propose a hierarchical modular network to bridge video representations and linguistic semantics at four granularities before generating captions: entity, verb, predicate, and sentence. Each level is implemented by one module to embed corresponding semantics into video representations. Additionally, we present a reinforcement learning module based on the scene graph of captions to better measure sentence similarity. Extensive experimental results show that the proposed method performs favorably against the state-of-the-art models on three widely-used benchmark datasets, including microsoft research video description corpus (MSVD), MSR-video to text (MSR-VTT), and video-and-TEXt (VATEX).

Three-Dimensional (3D) dense captioning is an emerging vision-language bridging task that aims to generate multiple detailed and accurate descriptions for 3D scenes. It presents significant potential and challenges due to its closer representation of the real world compared to 2D visual captioning, as well as complexities in data collection and processing of 3D point cloud sources. Despite the popularity and success of existing methods, there is a lack of comprehensive surveys summarizing the advancements in this field, which hinders its progress. In this paper, we provide a comprehensive review of 3D dense captioning, covering task definition, architecture classification, dataset analysis, evaluation metrics, and in-depth prosperity discussions. Based on a synthesis of previous literature, we refine a standard pipeline that serves as a common paradigm for existing methods. We also introduce a clear taxonomy of existing models, summarize technologies involved in different modules, and conduct detailed experiment analysis. Instead of a chronological order introduction, we categorize the methods into different classes to facilitate exploration and analysis of the differences and connections among existing techniques. We also provide a reading guideline to assist readers with different backgrounds and purposes in reading efficiently. Furthermore, we propose a series of promising future directions for 3D dense captioning by identifying challenges and aligning them with the development of related tasks, offering valuable insights and inspiring future research in this field. Our aim is to provide a comprehensive understanding of 3D dense captioning, foster further investigations, and contribute to the development of novel applications in multimedia and related domains.

Neural networks often make predictions relying on the spurious correlations from the datasets rather than the intrinsic properties of the task of interest, facing with sharp degradation on out-of-distribution (OOD) test data. Existing de-bias learning frameworks try to capture specific dataset bias by annotations but they fail to handle complicated OOD scenarios. Others implicitly identify the dataset bias by special design low capability biased models or losses, but they degrade when the training and testing data are from the same distribution. In this paper, we propose a General Greedy De-bias learning framework (GGD), which greedily trains the biased models and base model. The base model is encouraged to focus on examples that are hard to solve with biased models, thus remaining robust against spurious correlations in the test stage. GGD largely improves models’ OOD generalization ability on various tasks, but sometimes over-estimates the bias level and degrades on the in-distribution test. We further re-analyze the ensemble process of GGD and introduce the Curriculum Regularization inspired by curriculum learning, which achieves a good trade-off between in-distribution (ID) and out-of-distribution performance. Extensive experiments on image classification, adversarial question answering, and visual question answering demonstrate the effectiveness of our method. GGD can learn a more robust base model under the settings of both task-specific biased models with prior knowledge and self-ensemble biased model without prior knowledge. Codes are available at https://github.com/GeraldHan/GGD.

The target-dependent endonuclease activity (also known as the trans-cleavage activity) of CRISPR-Cas systems has stimulated great interest in the development of nascent sensing strategies for nucleic acid diagnostics. Despite many attempts, the majority of the sensitive CRISPR-Cas diagnostics strategies mainly rely on nucleic acid preamplification, which generally needs complex probes/primers designs, multiple experimental steps, and a longer testing time, as well as introducing the risk of false-positive results. In this work, we propose the CRISPR-Cas-Driven Single Micromotor (Cas-DSM), which can directly detect the nucleic acid targets at a single-molecule level with high specificity. We have demonstrated that the Cas-DSM is a reliable and practical method for the quantitative detection of DNA/RNA in various complex clinical samples as well as in individual cells without any preamplification processes. Due to the excellent features of the CRISPR/Cas system, including constant temperature, simple design, high specificity, and flexible programmability, the Cas-DSM could serve as a simple and universal platform for nucleic acid detection. More importantly, this work will provide a breakthrough for the development of next-generation amplification-free CRISPR/Cas sensing toolboxes.

Future activity anticipation is a challenging problem in egocentric vision. As a standard future activity anticipation paradigm, recursive sequence prediction suffers from the accumulation of errors. To address this problem, we propose a simple and effective Self-Regulated Learning framework, which aims to regulate the intermediate representation consecutively to produce representation that (a) emphasizes the novel information in the frame of the current time-stamp in contrast to previously observed content, and (b) reflects its correlation with previously observed frames. The former is achieved by minimizing a contrastive loss, and the latter can be achieved by a dynamic reweighing mechanism to attend to informative frames in the observed content with a similarity comparison between feature of the current frame and observed frames. The learned final video representation can be further enhanced by multi-task learning which performs joint feature learning on the target activity labels and the automatically detected action and object class tokens. SRL sharply outperforms existing state-of-the-art in most cases on two egocentric video datasets and two third-person video datasets. Its effectiveness is also verified by the experimental fact that the action and object concepts that support the activity semantics can be accurately identified.

In the context of climate change, drought is one of the most limiting factors that influence crop production. Maize, as a major crop, is highly vulnerable to water deficit, which causes significant yield loss. Thus, identification and utilization of drought-resistant germplasm are crucial for the genetic improvement of the trait. Here we report on a high-quality genome assembly of a prominent drought-resistant genotype, CIMBL55. Genomic and genetic variation analyses revealed that 65 favorable alleles of 108 previously identified drought-resistant candidate genes were found in CIMBL55, which may constitute the genetic basis for its excellent drought resistance. Notably, ZmRtn16, encoding a reticulon-like protein, was found to contribute to drought resistance by facilitating the vacuole H+-ATPase activity, which highlights the role of vacuole proton pumps in maize drought resistance. The assembled CIMBL55 genome provided a basis for genetic dissection and improvement of plant drought resistance, in support of global food security.

Weakly supervised Referring Expression Grounding (REG) aims to ground a particular target in an image described by a language expression while lacking the correspondence between target and expression. Two main problems exist in weakly supervised REG. First, the lack of region-level annotations introduces ambiguities between proposals and queries. Second, most previous weakly supervised REG methods ignore the discriminative location and context of the referent, causing difficulties in distinguishing the target from other same-category objects. To address the above challenges, we design an entity-enhanced adaptive reconstruction network (EARN). Specifically, EARN includes three modules: entity enhancement, adaptive grounding, and collaborative reconstruction. In entity enhancement, we calculate semantic similarity as supervision to select the candidate proposals. Adaptive grounding calculates the ranking score of candidate proposals upon subject, location and context with hierarchical attention. Collaborative reconstruction measures the ranking result from three perspectives: adaptive reconstruction, language reconstruction and attribute classification. The adaptive mechanism helps to alleviate the variance of different referring expressions. Experiments on five datasets show EARN outperforms existing state-of-the-art methods. Qualitative results demonstrate that the proposed EARN can better handle the situation where multiple objects of a particular category are situated together.

Single-wall carbon nanotubes in boron nitride (SWCNT@BN) are one-dimensional van der Waals heterostructures that exhibit intriguing physical and chemical properties. As with their carbon nanotube counterparts, these heterostructures can form from different combinations of chiralities, providing rich structures but also posing a significant synthetic challenge to controlling their structure. Enabled by advances in nanotube chirality sorting, clean removal of the surfactant used for solution processing, and a simple method to fabricate free-standing submonolayer films of chirality pure SWCNTs as templates for the BN growth, we show it is possible to directly grow BN on chirality enriched SWCNTs from solution processing to form van der Waals heterostructures. We further report factors affecting the heterostructure formation, including an accelerated growth rate in the presence of H2, and significantly improved crystallization of the grown BN, with the BN thickness controlled down to one single BN layer, through the presence of a Cu foil in the reactor. Transmission electron microscopy and electron energy-loss spectroscopic mapping confirm the synthesis of SWCNT@BN from the solution purified nanotubes. The photoluminescence peaks of both (7,5)- and (8,4)-SWCNT@BN heterostructures are found to redshift (by ∼10 nm) relative to the bare SWCNTs. Raman scattering suggests that the grown BN shells pose a confinement effect on the SWCNT core.

Squalene is a highly sought-after triterpene compound in growing demand, and its production offers a promising avenue for circular economy practices. In this study, we applied metabolic engineering principles to enhance squalene production in the nonconventional yeast Yarrowia lipolytica, using waste cooking oil as a substrate. By overexpressing key enzymes in the mevalonate pathway — specifically ERG9 encoding squalene synthase, ERG20 encoding farnesyl diphosphate synthase, and HMGR encoding hydroxy-methyl-glutaryl-CoA reductase — we achieved a yield of 779.9 mg/L of squalene. Further co-overexpression of DGA1, encoding diacylglycerol acyltransferase, and CAT2, encoding carnitine acetyltransferase, in combination with prior metabolic enhancements, boosted squalene production to 1381.4 mg/L in the engineered strain Po1g17. To enhance the supply of the precursor acetyl-CoA and inhibit downstream squalene conversion, we supplemented with 6 g/L pyruvic acid and 0.7 mg/L terbinafine, resulting in an overall squalene titer of 2594.1 mg/L. These advancements underscore the potential for sustainable, large-scale squalene production using Y. lipolyticacell factories, contributing to circular economy initiatives by valorizing waste materials.

Graphical abstract:

Mn catalysts have been designed based on OMS-2 support to optimize the catalytic activity in the degradation of organic pollutants.

The type V-I CRISPR-Cas system is becoming increasingly more attractive for genome editing. However, natural nucleases of this system often exhibit low efficiency, limiting their application. Here, we used structure-guided rational design and protein engineering to optimize an uncharacterized Cas12i nuclease, Cas12i3. As a result, we developed Cas-SF01, a Cas12i3 variant that exhibits significantly improved gene editing activity in mammalian cells. Cas-SF01 shows comparable or superior editing performance compared to SpCas9 and other Cas12 nucleases. Compared to natural Cas12i3, Cas-SF01 has an expanded PAM range and effectively recognizes NTTN and noncanonical NATN and TTVN PAMs. In addition, we identified an amino acid substitution, D876R, that markedly reduced the off-target effect while maintaining high on-target activity, leading to the development of Cas-SF01HiFi(high-fidelity Cas-SF01). Finally, we show that Cas-SF01 has high gene editing activities in mice and plants. Our results suggest that Cas-SF01 can serve as a robust gene editing platform with high efficiency and specificity for genome editing applications in various organisms.

Multi-sensor signal fusion is commonly used in associate with the artificial intelligence model to monitor tool wears. However, AI models equipped with limited multi-sensor training samples still exist problems: 1) The limitation of training samples may cause the AI model failure due to the intrinsic wear features contaminated by heavy noises. 2) The selection of multi-sensor signals as training samples is a difficult task for the negative impact on the recognition accuracy using inappropriate sensor features. Therefore, this paper proposes a denoise transformer Auto-Encoder (DTAE) as pre-processor for the tool condition monitoring (TCM) classifiers. The reconstruction task of the DTAE allows the model to pay more attention to the intrinsic wear features and the appropriate selection of them from the multi-sensor signals during feature extraction. Moreover, the loss function for DTAE ResNet is formed by summing the reconstruction loss from DTAE with the classification loss from ResNet. Compared DTAE ResNet to stacked sparse auto-encoder network, deep stacked auto-encoder network, ResNet-18, VGG-16, and LSTM, experiments demonstrated that the present method would attain the highest classification accuracies for tool wear suitable for TCM. And a comparative experiment was conducted to verify the effectiveness of the DTAE preprocessor in improving the anti-noise performance of the classifier.

Single-walled carbon nanotube (SWCNT) films exhibit exceptional optical and electrical properties, making them highly promising for scalable integrated devices. Previously, we employed SWCNT films as templates for the chemical vapor deposition (CVD) synthesis of one-dimensional heterostructure films where boron nitride nanotubes (BNNTs) and molybdenum disulfide nanotubes (MoS2NTs) were coaxially nested over the SWCNT networks. In this work, we have further refined the synthesis method to achieve precise control over the BNNT coating in SWCNT@BNNT heterostructure films. The resulting structure of the SWCNT@BNNT films was thoroughly characterized using a combination of electron microscopy, UV–vis–NIR spectroscopy, Fourier-transform infrared (FT-IR) spectroscopy, and Raman spectroscopy. Specifically, we investigated the pressure effect induced by BNNT wrapping on the SWCNTs in the SWCNT@BNNT heterostructure film and demonstrated that the shifts of the SWCNT’s G and 2D (G′) modes in Raman spectra can be used as a probe of the efficiency of BNNT coating. In addition, we studied the impact of vacuum annealing on the removal of the initial doping in SWCNTs, arising from exposure to ambient atmosphere, and examined the effect of MoO3doping in SWCNT films by using UV–vis–NIR spectroscopy and Raman spectroscopy. We show that through correlation analysis of the G and 2D (G′) modes in Raman spectra, it is possible to discern distinct types of doping effects as well as the influence of applied pressure on the SWCNTs within SWCNT@BNNT heterostructure films. This work contributes to a deeper understanding of the strain and doping effect in both SWCNTs and SWCNT@BNNTs, thereby providing valuable insights for future applications of carbon-nanotube-based one-dimensional heterostructures.

Immunoglobulin is an essential component of the body’s defense against pathogens, aiding in the recognition and clearance of foreign antigens. Research concerning immunoglobulin gene and its diversity of expression across different breeds within the same species is relatively scarce. In this study, we employed RACE (Rapid Amplification of cDNA Ends) technology, prepared DNA libraries, performed high-throughput sequencing, and conducted related bioinformatics analysis to analyze the differences in immunoglobulin gene diversity and expression at different periods in Hy-line brown hens, Lueyang black-bone chickens, and Beijing-You chickens. The study found that the composition of chicken immunoglobulin genes is relatively simple, with both the light chain and heavy chain having a functional V gene. Additionally, the mechanisms of immunoglobulin diversity generation tended to be consistent among different breeds and periods of chickens, primarily relying on abundant junctional diversity, somatic hypermutation (SHM), and gene conversion (GCV) to compensate for the limitations of low-level V(D)J recombination. As the age increased, the junctional diversity of IgH and IgL tended to diversify and showed similar expression patterns among different breeds. In the three chicken breeds, the predominant types of mutations observed in IGHV and IGLV SHM were A to G and G to A transitions. Specifically, IGLV exhibited a preference for A to G mutations, whereas IGHV displayed a bias toward G to A mutations. The regions at the junctions between framework regions (FR) and complementarity-determining regions (CDR) and within the CDR regions themselves are typically prone to mutations. The locations of GCV events in IGLV and IGHV do not show significant differences, and replacement segments are concentrated in the central regions of FR1, CDR, and FR2. Importantly, gene conversion events are not random occurrences. Additionally, our investigation revealed that CDRH3 in chickens of diverse breeds and periods the potential for diversification through the incorporation of cysteine. This study demonstrates that the diversity of immunoglobulin expression tends to converge among Hy-line brown hens, Lueyang black-bone chickens, and Beijing-You chickens, indicating that the immunoglobulin gene expression mechanisms in different breeds of chickens do not exhibit significant differences due to selective breeding.This study demonstrates the convergence of immunoglobulin gene expression patterns among Hy-line brown hens, Lueyang black-bone chickens, and Beijing-You chickens, implying that the immunoglobulin gene expression mechanisms in different chicken breeds do not exhibit significant variations resulting from selective breeding.Immunoglobulins play a key role in the organism’s defense against pathogens, and their diverse expression allows the body to generate a wide array of antibodies. This diversity serves as a critical safeguard for the immune system against various pathogens. Natural geographical variances and artificial breeding and selection can potentially lead to different immune responses in distinct populations of the same species when confronted with the same pathogen. In this study, we investigated the diversity of immunoglobulin gene expression in the natural state of different chicken breeds (Hy-line brown hens, Lueyang black-bone chickens, and Beijing-You chickens) and at different periods from the perspective of immunoglobulin gene expression mechanism. We analyzed the diversity of immunoglobulin based on the results of high-throughput sequencing by extracting Fabricius bursa RNA, RACE (Rapid Amplification of cDNA Ends) technique, and constructing DNA libraries. Our study reveals that the junctional diversity, somatic hypermutation, CDR3 diversity, and gene conversion expression of immunoglobulins in Hy-line brown hens, Lueyang black-bone chickens, and Beijing-You chickens converge during the same time period. This indicates that the immunoglobulin gene expression mechanisms in different chicken breeds do not exhibit significant variations as a result of selective breeding.

Viruses are ubiquitous in human life. Some viruses can be used as vectors of genetic engineering and specific pesticides. Other viruses trigger a variety of diseases in humans, animals and plants, resulting in high infection rates and mortality. Therefore, convenient, accurate and rapid detection of viruses is of great significance for the diagnosis and treatment of subsequent diseases. In contrast to traditional methods of detection, which rely on time-consuming and complex techniques such as polymerase chain reaction (PCR), fluorescent probes and imaging methods generate real-time results, with high specificity, and have been widely used in viral detection. In this review, the application of viral fluorescent probes in analyzing the molecular structure, detection and biological imaging is discussed. In particular, we categorized the probes based on their specificity for human and plant viruses, reviewing the latest findings and analyzing their limitations. The potential of fluorescent molecular probes in the treatment of viral disease and environmental analysis, and their possible combinations with protein and immune technology are discussed.

Alzheimer’s disease (AD) is the most common neurodegenerative disease among the elderly. Abnormal aggregates of both β-amyloid peptide (Aβ) subtypes, Aβ42and Aβ40, are the typical neuropathology hallmarks of AD. However, because of the lack of specific recognition elements such as an antibody and aptamer, it is difficult to differentiate and determine the oligomers of Aβ42and Aβ40in clinic. In this paper, we developed a planar bilayer lipid membrane (BLM)-based electrochemical biosensor. According to the dynamic differences on oligomer-induced BLM damage, both low-mass, soluble oligomers of Aβ42and Aβ40(L-Aβ42O and L-Aβ40O) were measured in turn by electrochemical impedance spectroscopy. The BLM was supported by a porous 11-mercaptoundecanoic acid layer on a gold electrode, which amplified the impedance signal corresponding to the membrane damage and improved the detection sensitivity. The weakly charged surface of the BLM ensured the low non-specific adsorption of coexisting proteins in cerebrospinal fluid (CSF). Using the electrochemical biosensor, L-Aβ42O was determined within 20 min, with a linear range from 5 to 500 pM and a detection limit of 3 pM. Meanwhile, L-Aβ40O was determined within 60 min, with a linear range from 60 pM to 6.0 nM and a detection limit of 26 pM. The recoveries in oligomer-spiked artificial CSF and human CSF samples confirmed the accuracy and applicability of this proposed method in clinic. This work provides an antibody-free, highly selective, and sensitive method for simultaneous detections of L-Aβ42O and L-Aβ40O in real CSF samples, which is significant for the early diagnosis and prognosis of AD.

The sandstone layers of the Upper Paleozoic tight clastic gas reservoirs in the Ordos Basin are generally distributed in a pattern of nearly NS strip, and the channel branches and intersects frequently. A single sand body is in a multilayered contact mode resulted from lateral accretion, and the sand bodies at the river intersections present a feature of lying in the nearly EW direction, which brings great difficulties to the geo-steering of horizontal wells. In order to improve the reservoir drilling rate of horizontal wells, this paper systematically analyzed the geo-steering status of horizontal wells and the sedimentary characteristics of reservoirs. Then, the spatial distribution of reservoirs was predicted using 3D geological modeling and 3D seismic. In addition, based on the cognitions on the space distribution of sand bodies from the drilled horizontal wells, the horizontal well geo-steering technology and method were constantly improved and enriched. Thus, an integrated steering technology of “fine sublayer correlation for target entering, geology in small scale, and seismic in large scale” based on in-depth integration of multidisciplinary thinking was newly formed, and it was also applied on site. And the following research results were obtained. First, under the guidance of the sedimentation model, the target entering process is controlled precisely and the success rate of one-trip target entering is improved, so it is one important method for the target steering of deviated hole sections. Second, geological modeling can guide the drilling of horizontal wells, but to some extent, it is deviated from the real underground geologic bodies, so it can be used as an auxiliary horizontal-well steering method. Third, 3D seismic steering can tell the boundary of complex river channel and discriminate the spatial relative location of predominant sand bodies, so it is the primary method for horizontal-well steering to provide excellent judgment and guidance on the steering of horizontal hole sections. Fourth, owing to the application of this new method in 62 horizontal wells drilled in the tight gas demonstration area, the average horizontal section length reaches 1430 m, the average sandstone drilling rate is 86.2%, the average gas layer drilling rate is 70.2%, and the gas layer drilling rate of horizontal wells is increased by more than 10%.

Fucoxanthin (Fx), an allenic carotenoid from brown seaweeds or diatoms, has been demonstrated to prevent obesity. Gut dysbiosis and inflammation are two counted important incidence reasons of obesity and related diseases. In this paper, a mouse model induced by high-fat diet (HFD) was used to reveal the role of Fx in modulating intestinal homeostasis and treating obesity. In addition, 16S rRNA sequencing results inferred that Fx alleviated HFD-induced gut microbiota dysbiosis by significantly inhibiting the growth of obesity-/inflammation-related Lachnospiraceae and Erysipelotrichaceae while promoting the growth of Lactobacillus/Lactococcus, Bifidobacterium, and some butyrate-producing bacteria. The correlation analysis showed that some gut microbiota taxa were strongly correlated with obesity phenotypes and the inflammation level. In conclusion, dietary Fx has the potential to alleviate the development of obesity and related symptoms through mediating the composition of gut microbiota as demonstrated in mice. This study provides scientific evidence for the potential effects of Fx on obesity treatment.

The photoinitiation abilities of three 1,2‐diketones [i.e., acenaphthenequinone (ANPQ), aceanthrenequinone (AATQ), and 9,10‐phenanthrenequinone (PANQ)]‐based photoinitiating systems [PISs, with additives such as iodonium salt, N‐vinylcarbazole (NVK), tertiary amine, and phenacyl bromide (R‐Br)] for cationic photopolymerization and free‐radical photopolymerization under the irradiation of ultraviolet (UV; 392 nm) or blue (455 nm) light‐emitting diode (LED) bulb are investigated. All 1,2‐diketones studied exhibit ground state absorption that match with the emission spectra of UV (392 nm) or blue LED (455 nm) better than that of the well‐known blue‐light‐sensitive photoinitiator camphorquinone (CQ). In particular, AATQ/iodonium salt/NVK can show high photoinitiating ability (with epoxide conversion yield >70%) under the UV light irradiation due to the effect of NVK. In addition, 1,2‐diketone/iodonium salt (and optional NVK) systems are capable of initiating free‐radical photopolymerization of methacrylates, with conversions of 50–58%. Furthermore, some 1,2‐diketone/tertiary amine (and optional R‐Br) combinations are found to demonstrate high efficiency to initiate free‐radical photopolymerization, and 71% of methacrylate conversion can be achieved with PANQ/tertiary amine/R‐Br PIS. Some 1,2‐ketone‐based PISs can even exhibit higher efficiency than the CQ‐based systems. The photochemical mechanism of the radical generation from the 1,2‐diketone‐based PISs is investigated and found to be consistent with the related photopolymerization efficiency. © 2020 Wiley Periodicals, Inc. J. Polym. Sci. 2020, 58, 792–802 Three 1,2‐diketones (i.e., acenaphthenequinone, aceanthrenequinone, and 9,10‐phenanthrenequinone)‐based photoinitiating systems (PISs, with additives such as iodonium salt, N‐vinylcarbazole, tertiary amine, and phenacyl bromide) exhibit the ability to initiate both the free‐radical and the cationic photopolymerization under the ultraviolet or blue light‐emitting diode. Most of the investigated 1,2‐diketones‐based PISs are even more efficient than the well‐known camphorquinone‐based systems.

Type VII secretion systems (T7SSs) are found in many disease related bacteria including Mycobacterium tuberculosis(Mtb). ESX-1 [early secreted antigen 6 kilodaltons (ESAT-6) system 1] is one of the five subtypes (ESX-1~5) of T7SSs in Mtb, where it delivers virulence factors into host macrophages during infection. However, little is known about the molecular details as to how this occurs. Here, we provide high-resolution crystal structures of the C-terminal ATPase3domains of EccC subunits from four different MtbT7SS subtypes. These structures adopt a classic RecA-like ɑ/βfold with a conserved Mg-ATP binding site. The structure of EccCb1 in complex with the C-terminal peptide of EsxB identifies the location of substrate recognition site and shows how the specific signaling module “LxxxMxF” for MtbESX-1 binds to this site resulting in a translation of the bulge loop. A comparison of all the ATPase3structures shows there are significant differences in the shape and composition of the signal recognition pockets across the family, suggesting that distinct signaling sequences of substrates are required to be specifically recognized by different T7SSs. A hexameric model of the EccC-ATPase3is proposed and shows the recognition pocket is located near the central substrate translocation channel. The diameter of the channel is ~25-Å, with a size that would allow helix-bundle shaped substrate proteins to bind and pass through. Thus, our work provides new molecular insights into substrate recognition for MtbT7SS subtypes and also a possible transportation mechanism for substrate and/or virulence factor secretion.

Phosphorylated proteins play important roles in the pathogenesis of Alzheimer’s disease (AD). The most abundant constituent in AD’s brain deposit is the amyloid-β40peptide (Aβ40). Based on it, the degree of phosphorylated Aβ40in body fluids (e.g., cerebrospinal fluid, CSF), which is defined by the ratio of phosphorylated Aβ40to total Aβ40(pAβ40/tAβ40), is anticipated to be an index for early diagnosis of AD. The major challenge in pAβ40/tAβ40detection is the large concentration difference between two Aβ40forms in the real samples, which usually requires multichannel equipment and complicated detection process. In this paper, we revealed the unexpected close affinities of the anti-Aβ40antibody to Aβ40(40.2 nM–1) and to pAβ40(42.3 nM–1). Based on it, a convenient coimmunocapture and electrochemical quantitation of tAβ40and pAβ40was achieved on an anti-Aβ40antibody immobilized Au electrode (anti-Aβ40/Au). Once Aβ40and pAβ40were synchronously captured on the anti-Aβ40/Au electrode, the tAβ40levels in CSF samples were quantified with electrochemical impedance spectroscopy. With the signal amplification from Cd2+/Ti4+-functionalized titanium phosphate nanospheres (Cd2+/Ti4+@TiP) which was selective conjugated to pAβ40, concentrations of low abundant pAβ40as low as 1 fM were readily measured by square wave voltammetry. Our results reveal that despite the concentrations of tAβ40and pAβ40fluctuate in each individual case, the concentration ratios of pAβ40/tAβ40in CSF samples from AD patients are significant larger than those from healthy donors. It demonstrates that the degree of phosphorylated Aβ40is hopeful to be an effective index for evaluating the AD progress and improving the accuracy of clinic AD diagnosis.

All-inorganic perovskite solar cells (pero-SCs) are attracting considerable attention due to their promising thermal stability, but their inferior power-conversion efficiency (PCE) and moisture instability are hindering their application. Here, we used a gradient thermal annealing (GTA) method to control the growth of α-CsPbI2Br crystals and then utilized a green anti-solvent (ATS) isopropanol to further optimize the morphology of α-CsPbI2Br film. Through this GTA-ATS synergetic effect, the growth of α-CsPbI2Br crystals could be precisely controlled, leading to a high-quality perovskite film with one-micron average grain size, low root-mean-square of 25.9 nm, and reduced defect density. Pero-SCs based on this CsPbI2Br film achieved a champion scan PCE of 16.07% (stabilized efficiency of 15.75%), which is the highest efficiency reported in all-inorganic pero-SCs. Moreover, the CsPbI2Br pero-SC demonstrates excellent robustness against moisture and oxygen, and maintains 90% of initial PCE after aging 120 hr under 100 mW/cm2UV irradiation.

Cobalt (Co) with its low resistivity, excellent resistance to electro-migration with co-deposition property and void-free seamless fill ability, pledges to transform the landscape of integrated circuits in many areas, especially in logic contacts and interconnects. Chemical mechanical polishing (CMP), which utilizes the synergistic action of chemical corrosion and mechanical wear, has been recognized as the exclusive manufacturing approach to achieve global and local planarization of wafer surfaces. In this work, we proposed an innovative hydrogen peroxide (HP) polishing slurry, applying phthalic acid as the complexing agent and oleic acid as the corrosion inhibitor at pH 10. From the results of appropriate material removal/static etching rates as well as the smooth surface morphologies, phthalic acid and oleic acid are identified to be qualified in HP-based slurries for heterogeneous materials of Co interconnects. Moreover, the mechanisms of complexation and inhibition have been revealed by electrochemical analysis and X-ray photoelectron spectroscopy tests. It can be concluded that with the addition of complexing agent phthalic acid in HP-based slurries, the transformation of oxidization from low-valence compounds to high-valence was partially replaced by stronger complexing action, making the removal mechanism be attributed to the combined oxidization and complexation. When oleic acid is introduced, it could react with Co oxides to form a polymer protection layer adsorbing on Co films, achieving an inhibition effect to avoid Co excessive corrosion. Meanwhile, the oxidization of HP as well as the complexation of phthalic acid, combined with the protection of oleic acid play critical roles to maintain the appropriate removal rates and selection ratios.

ABSTRACTThe human immunodeficiency virus-1 (HIV-1) regulatory protein Tat plays an important role during HIV-1-associated neurocognitive disorders (HAND) by inducing neuronal autophagy. In this study, we used immunohistochemistry, immunofluorescence, western blot, qRT-PCR, and RNA interference to elucidate the involvement of Bcl-2-associated athanogene 3 (BAG3) in the pathogenesis of HIV-1 Tat-induced autophagy during HAND. We found that BAG3 expression is elevated in astrocytes in frontal cortex of macaques infected with simian immunodeficiency virus-human immunodeficiency chimeric virus (SHIV). In addition, in human primary glioblastoma cells (U87), HIV-1 Tat upregulated BAG3 in an NF-κB-dependent manner to induce autophagy. Importantly, suppression of BAG3 or inhibition of NF-κB activity reversed the HIV-1 Tat-induced autophagy. These results indicate that HIV-1 Tat induces autophagy by upregulating BAG3 via NF-κB signaling, which suggests BAG3 and NF-κB could potentially serve as novel targets for HAND therapies.

Astaxanthin (Ax), a type of carotenoid, has limited use as a result of its poor water solubility, low bioavailability, and decomposition under harsh conditions. This study reports a delivery system for Ax through a simple affinity binding with β-lactoglobulin and then coated with chitosan oligosaccharides. Ax-loaded β-lactoglobulin nanocomplexes and chitosan oligosaccharide-coated nanocomplexes were successfully prepared. The nanocomplexes exhibited a smooth spherical shape with diameters of about 40 and 60 nm measured by transmission electron microscopy. Spectroscopic techniques (ultraviolet–visible, fluorescence, and Fourier transform infrared spectroscopy) combined with molecular docking were used to determine the binding mechanism of Ax and β-lactoglobulin. In comparison to native Ax, the nanocomplexes maintain the hydroxyl radical scavenging activity of Ax under the treatment of acid, high temperature, and ultraviolet radiation. The release experiment of nanocomplexes revealed that the encapsulation could provide prolonged release of Ax in simulated gastrointestinal juices. This study aimed to fabricate and characterize Ax−β-lactoglobulin nanocomplexes, which can improve the Ax stability and slow release.