Framework for Generation and Removal of Multiple Types of Adverse Weather from Driving Scene Images.

Weather variation in the distribution of image data can cause a decline in the performance of existing visual algorithms during evaluation. Adding additional samples of target domain to training data or using pre-trained image restoration methods such as de-hazing, de-raining, and de-snowing, to improve the quality of input images are two promising solutions. In this work, we propose Multiple Weather Translation GAN (MWTG), a CycleGAN-based, dual-purpose framework that simultaneously learns weather generation and its removal from image data. MWTG consists of four GANs constrained using cycle consistency that carry out domain translation tasks between hazy, rainy, snowy, and clear weather, using an asymmetric approach. To increase network capacity, we employ a spatial feature transform (SFT) layer to fuse the features extracted from the weather layer, which contains high-level domain information from the previous generators. Further, we collect an unpaired, real-world driving dataset recorded under various weather conditions called Realistic Driving Scenes under Bad Weather (RDSBW). We qualitatively and quantitatively evaluate MWTG using the RDSBW and the variation of Cityscapes that synthesize weather effects, eg., FoggyCityscape. Our experimental results suggest that MWTG can generate realistic weather in clear images and also accurately remove noise from weather images. Furthermore, the SOTA pedestrian detector ASCP is shown to achieve an impressive gain in detection precision after image restoration using the proposed MWTG method.

Controllable Unsupervised Snow Synthesis by Latent Style Space Manipulation.

In the field of intelligent vehicle technology, there is a high dependence on images captured under challenging conditions to develop robust perception algorithms. However, acquiring these images can be both time-consuming and dangerous. To address this issue, unpaired image-to-image translation models offer a solution by synthesizing samples of the desired domain, thus eliminating the reliance on ground truth supervision. However, the current methods predominantly focus on single projections rather than multiple solutions, not to mention controlling the direction of generation, which creates a scope for enhancement. In this study, we propose a generative adversarial network (GAN)-based model, which incorporates both a style encoder and a content encoder, specifically designed to extract relevant information from an image. Further, we employ a decoder to reconstruct an image using these encoded features, while ensuring that the generated output remains within a permissible range by applying a self-regression module to constrain the style latent space. By modifying the hyperparameters, we can generate controllable outputs with specific style codes. We evaluate the performance of our model by generating snow scenes on the Cityscapes and the EuroCity Persons datasets. The results reveal the effectiveness of our proposed methodology, thereby reinforcing the benefits of our approach in the ongoing evolution of intelligent vehicle technology.

L-DIG: A GAN-Based Method for LiDAR Point Cloud Processing under Snow Driving Conditions.

LiDAR point clouds are significantly impacted by snow in driving scenarios, introducing scattered noise points and phantom objects, thereby compromising the perception capabilities of autonomous driving systems. Current effective methods for removing snow from point clouds largely rely on outlier filters, which mechanically eliminate isolated points. This research proposes a novel translation model for LiDAR point clouds, the 'L-DIG' (LiDAR depth images GAN), built upon refined generative adversarial networks (GANs). This model not only has the capacity to reduce snow noise from point clouds, but it also can artificially synthesize snow points onto clear data. The model is trained using depth image representations of point clouds derived from unpaired datasets, complemented by customized loss functions for depth images to ensure scale and structure consistencies. To amplify the efficacy of snow capture, particularly in the region surrounding the ego vehicle, we have developed a pixel-attention discriminator that operates without downsampling convolutional layers. Concurrently, the other discriminator equipped with two-step downsampling convolutional layers has been engineered to effectively handle snow clusters. This dual-discriminator approach ensures robust and comprehensive performance in tackling diverse snow conditions. The proposed model displays a superior ability to capture snow and object features within LiDAR point clouds. A 3D clustering algorithm is employed to adaptively evaluate different levels of snow conditions, including scattered snowfall and snow swirls. Experimental findings demonstrate an evident de-snowing effect, and the ability to synthesize snow effects.

Pore architecture of TRIC channels and insights into their gating mechanism.

Intracellular Ca2+ signalling processes are fundamental to muscle contraction, neurotransmitter release, cell growth and apoptosis. Release of Ca2+ from the intracellular stores is supported by a series of ion channels in sarcoplasmic or endoplasmic reticulum (SR/ER). Among them, two isoforms of the trimeric intracellular cation (TRIC) channel family, named TRIC-A and TRIC-B, modulate the release of Ca2+ through the ryanodine receptor or inositol triphosphate receptor, and maintain the homeostasis of ions within SR/ER lumen. Genetic ablations or mutations of TRIC channels are associated with hypertension, heart disease, respiratory defects and brittle bone disease. Despite the pivotal function of TRIC channels in Ca2+ signalling, their pore architectures and gating mechanisms remain unknown. Here we present the structures of TRIC-B1 and TRIC-B2 channels from Caenorhabditis elegans in complex with endogenous phosphatidylinositol-4,5-biphosphate (PtdIns(4,5)P2, also known as PIP2) lipid molecules. The TRIC-B1/B2 proteins and PIP2 assemble into a symmetrical homotrimeric complex. Each monomer contains an hourglass-shaped hydrophilic pore contained within a seven-transmembrane-helix domain. Structural and functional analyses unravel the central role of PIP2 in stabilizing the cytoplasmic gate of the ion permeation pathway and reveal a marked Ca2+-induced conformational change in a cytoplasmic loop above the gate. A mechanistic model has been proposed to account for the complex gating mechanism of TRIC channels.

Optimization of extraction process and the antioxidant activity spectrum-effect relationship of Angelica dahurica.

Despite the large number of studies indicating that Angelica dahurica has strong antioxidant capacity, there are no clear details on the specific antioxidant components involved. In this study, the chromatograms and antioxidant activity of A. dahurica were obtained by gas chromatography-mass spectrometry (GC-MS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and ferric ion reducing antioxidant power (FRAP) methods. The factors affecting free radical scavenging were investigated under different extraction conditions, on the basis of the single-factor experiment. The results showed that the optimum conditions for the DPPH method were ultrasonic extraction, using 80% methanol as extract the extraction solvent, a 20:1 (ml/g) ratio of liquid to material and an extraction time of 30 min. Furthermore, the spectrum-effect relationship between the GC-MS chromatograms and the antioxidant effect of A. dahurica was established to evaluate the antioxidant components of A. dahurica using multiple data analysis methods. Isoimperatorin and byakangelicol made the greatest contribution to scavenging DPPH free radicals and ferric-reducing antioxidant power. This result may provide the basis for developing new and effective products based on the antioxidant ingredients of A. dahurica.

Assessment of the expression of the immune checkpoint molecules PD-1, CTLA4, TIM-3 and LAG-3 across different cancers in relation to treatment response, tumor-infiltrating immune cells and survival.

Immune checkpoint molecules have been identified as crucial regulators of the immune response, which motivated the emergence of immune checkpoint-targeting therapeutic strategies. However, the prognostic significance of the immune checkpoint molecules PD-1, CTLA4, TIM-3 and LAG-3 remains controversial. The aim of our study was to conduct a systematic assessment of the expression of these immune checkpoint molecules across different cancers in relation to treatment response, tumor-infiltrating immune cells and survival. Oncomine and PrognoScan database analyses were used to investigate the expression levels and prognostic values of these immune checkpoint molecule genes across various cancers. Then, we used Kaplan-Meier plotter to validate the associations between the checkpoint molecules and cancer survival identified in the PrognoScan analysis. TIMER analysis was used to evaluate immune cell infiltration data from The Cancer Genome Atlas. Finally, we used Gene Expression Profiling Interactive Analysis to investigate the prognostic value of these four checkpoint molecules and assess the correlations between these four checkpoint molecules and genetic markers. These immune checkpoint molecules may potentially serve as prognostic factors and therapeutic targets in breast cancer, ovarian cancer and lung cancer. The prognostic roles of these checkpoint molecules varied greatly across cancers, which implied a noteworthy amount of heterogeneity among tumors, even within the same molecular subtype. In addition, the expression patterns of these checkpoint molecules were closely associated with treatment response and provided some useful direction when choosing chemotherapeutic drugs. These findings enhance our understanding of these checkpoints in cancer treatment and identify strategies to promote synergistic activities in the context of other immunotherapies.

Mid-infrared widely tunable single-mode interband cascade lasers based on V-coupled cavities.

We demonstrate widely tunable single-mode V-coupled-cavity lasers emitting at wavelengths near 3 µm based on a type-II interband cascade (IC) structure. The mode selection is achieved using a half-wave V-coupler designed for the IC structure in the mid-infrared range. The laser waveguides and cavity structure are deeply etched in a single etching step, without any grating. By changing the injection current at a fixed heat-sink temperature, a tuning range over 35 nm can be achieved with a side-mode suppression-ratio up to 28 dB. The tuning range can be extended to 60 nm when combined with the adjustments of the heat-sink temperature.

Ion- and water-binding sites inside an occluded hourglass pore of a trimeric intracellular cation (TRIC) channel.

BACKGROUND: Trimeric intracellular cation (TRIC) channels are crucial for Ca2+ handling in eukaryotes and are involved in K+ uptake in prokaryotes. Recent studies on the representative members of eukaryotic and prokaryotic TRIC channels demonstrated that they form homotrimeric units with the ion-conducting pores contained within each individual monomer. RESULTS: Here we report detailed insights into the ion- and water-binding sites inside the pore of a TRIC channel from Sulfolobus solfataricus (SsTRIC). Like the mammalian TRIC channels, SsTRIC is permeable to both K+ and Na+ with a slight preference for K+, and is nearly impermeable to Ca2+, Mg2+, or Cl-. In the 2.2-Å resolution K+-bound structure of SsTRIC, ion/water densities have been well resolved inside the pore. At the central region, a filter-like structure is shaped by the kinks on the second and fifth transmembrane helices and two nearby phenylalanine residues. Below the filter, the cytoplasmic vestibule is occluded by a plug-like motif attached to an array of pore-lining charged residues. CONCLUSIONS: The asymmetric filter-like structure at the pore center of SsTRIC might serve as the basis for the channel to bind and select monovalent cations. A Velcro-like plug-pore interacting model has been proposed and suggests a unified framework accounting for the gating mechanisms of prokaryotic and eukaryotic TRIC channels.

The ubiquitin codes in cellular stress responses.

Ubiquitination/ubiquitylation, one of the most fundamental post-translational modifications, regulates almost every critical cellular process in eukaryotes. Emerging evidence has shown that essential components of numerous biological processes undergo ubiquitination in mammalian cells upon exposure to diverse stresses, from exogenous factors to cellular reactions, causing a dazzling variety of functional consequences. Various forms of ubiquitin signals generated by ubiquitylation events in specific milieus, known as ubiquitin codes, constitute an intrinsic part of myriad cellular stress responses. These ubiquitination events, leading to proteolytic turnover of the substrates or just switch in functionality, initiate, regulate, or supervise multiple cellular stress-associated responses, supporting adaptation, homeostasis recovery, and survival of the stressed cells. In this review, we attempted to summarize the crucial roles of ubiquitination in response to different environmental and intracellular stresses, while discussing how stresses modulate the ubiquitin system. This review also updates the most recent advances in understanding ubiquitination machinery as well as different stress responses and discusses some important questions that may warrant future investigation.

A haplotype-resolved gap-free genome assembly provides novel insight into monoterpenoid diversification in Mentha suaveolens 'Variegata'.

Mentha is a commonly used spice worldwide, which possesses medicinal properties and fragrance. These characteristics are conferred, at least partially, by essential oils such as menthol. In this study, a gap-free assembly with a genome size of 414.3 Mb and 31,251 coding genes was obtained for Mentha suaveolens 'Variegata'. Based on its high heterozygosity (1.5%), two complete haplotypic assemblies were resolved, with genome sizes of 401.9 and 405.7 Mb, respectively. The telomeres and centromeres of each haplotype were almost fully annotated. In addition, we detected a total of 41,135 structural variations. Enrichment analysis demonstrated that genes involved in terpenoid biosynthesis were affected by these structural variations. Analysis of volatile metabolites showed that M. suaveolens mainly produces piperitenone oxide rather than menthol. We identified three genes in the M. suaveolens genome which encode isopiperitenone reductase (ISPR), a key rate-limiting enzyme in menthol biosynthesis. However, the transcription levels of ISPR were low. Given that other terpenoid biosynthesis genes were expressed, M. suaveolens ISPRs may account for the accumulation of piperitenone oxide in this species. The findings of this study may provide a valuable resource for improving the detection rate and accuracy of genetic variants, thereby enhancing our understanding of their impact on gene function and expression. Moreover, our haplotype-resolved gap-free genome assembly offers novel insights into molecular marker-assisted breeding of Mentha.

Simultaneous Determination of the Content of Isoimperatorin, Imperatorin, Oxypeucedanin, Xanthotoxol and Byakangelicin in Angelica dahurica by HPTLC Scanning.

In this study, we established a new rapid, simple and low cost method for the determination of coumarin components in Angelica dahurica using high-performance thin-layer chromatography (HPTLC) based on the standards of the Chinese Pharmacopoeia for the analysis of isoimperatorin, imperatorin, oxypeucedanin, xanthotoxol and byakangelicin. The coumarins in A. dahurica were extracted with solvent methods, and linear ascending development was carried out in a twin trough glass chamber saturated with petroleum ether-ethyl acetate (3:2, v/v). The plate was dried and analyzed by HPTLC scanner at 254 nm. The five coumarin components have achieved good separation, clear and satisfactory resolution with the Rf values of 0.84, 0.69, 0.64, 0.57 and 0.19 for isoimperatorin, imperatorin, oxypeucedanin, xanthotoxol and byakangelicin, respectively. The content of five coumarins were 0.282, 0.626, 0.393, 0.066 and 0.144, respectively. In addition, the calibration range was constructed in the range 0.8-4.0 µg/spot; the limit of detection and limit of quantification, precision, repeatability and recovery were stably and good. This study indicated that the HPTLC scanning could be used for the determination of multiple components in A. dahurica.

Mitochondrial quality control in the brain: The physiological and pathological roles.

The human brain has high energetic expenses and consumes over 20% of total oxygen metabolism. Abnormal brain energy homeostasis leads to various brain diseases. Among multiple factors that contribute to these diseases, mitochondrial dysfunction is one of the most common causes. Maintenance of mitochondrial integrity and functionality is of pivotal importance to brain energy generation. Mitochondrial quality control (MQC), employing the coordination of multiple mechanisms, is evolved to overcome many mitochondrial defects. Thus, not surprisingly, aberrant mitochondrial quality control results in a wide range of brain disorders. Targeting MQC to preserve and restore mitochondrial function has emerged as a promising therapeutic strategy for the prevention and treatment of brain diseases. Here, we set out to summarize the current understanding of mitochondrial quality control in brain homeostasis. We also evaluate potential pharmaceutically and clinically relevant targets in MQC-associated brain disorders.

Biosynthetic regulatory network of flavonoid metabolites in stems and leaves of Salvia miltiorrhiza.

Flavonoid secondary metabolites can treat and prevent many diseases, but systematic studies on regulation of the biosynthesis of such metabolites in aboveground parts of Salvia miltiorrhiza are lacking. In this study, metabonomic and transcriptomic analyses of different S. miltiorrhiza phenotypes were conducted to explore pathways of synthesis, catalysis, accumulation, and transport of the main flavonoid secondary metabolites regulating pigment accumulation. Tissue localization and quantitative analysis of flavonoid secondary metabolites were conducted by laser scanning confocal microscopy (LSCM). A total 3090 differentially expressed genes were obtained from 114,431 full-length unigenes in purple and green phenotypes, and 108 functional genes were involved in flavonoid biosynthesis. Five key phenylpropane structural genes (PAL, 4CL, ANS, 3AT, HCT) were highly differentially expressed, and four transcription factor genes (MYB, WRKY, bHLH, bZiP) were identified. In addition, six GST genes, nine ABC transporters, 22 MATE genes, and three SNARE genes were detected with key roles in flavonoid transport. According to LSCM, flavonoids were mainly distributed in epidermis, cortex, and collenchyma. Thus, comprehensive and systematic analyses were used to determine biosynthesis, accumulation, and transport of flavonoids in stems and leaves of different S. miltiorrhiza phenotypes. The findings will provide a reference for flavonoid production and cultivar selection.

Determination of Five Coumarins in Angelicae Pubescentis Radix from Different Origins by HPTLC-Scanning.

The HPTLC method is widely used in the field of quality evaluation and component analysis of traditional Chinese medicine (TCM). This work developed an HPTLC method to determine the five effective components of osthole, columbianadin, isoimperatorin, oxypeucedanin, and imperatorin in Angelicae Pubescentis Radix (APR) from twelve different origins, and the quality difference was analyzed by comprehensive factor analysis and cluster analysis. The results showed that the calibration curves of five components exhibited good linearity within the linear ranges (0.8-4.0 µg). The RSD of precision was 1.06%-1.21%, and the repeatability and stability tests were good. The results of cluster analysis showed that the APR from 12 different areas was divided into two categories, and at the same time, it was found that the quality of Dazhou in Sichuan and Huating in Gansu was better than in other areas. In this study, a simple, rapid, and efficient method for quality evaluation of TCM was established by the HPTLC method.

Purification of Mitochondrial Ribosomes with the Translocase Oxa1L from HEK Cells.

Mitochondrial ribosomes (mitoribosomes) perform protein synthesis inside mitochondria, the organelles responsible for energy conversion and adenosine triphosphate (ATP) production in eukaryotic cells. To investigate their functions and structures, large-scale purification of intact mitoribosomes from mitochondria-rich animal tissues or HEK cells have been developed. However, the fast purification of mitoribosomes anchored to the mitochondrial inner membrane in complex with the Oxa1L translocase remains particularly challenging. Herein, we present a protocol recently developed and modified in our lab that provides details for the efficient isolation of intact mitoribosomes with its translocase Oxa1L. We combined the cell culture of PDE12-/- or wild-type HEK293 cell lines with the isolation of mitochondria and the purification steps used for the biochemical and structural studies of mitoribosomes and Oxa1L. Graphic abstract: Schematic procedure for the purification of mitoribosomes from HEK cells. The protocol described herein includes two main sections: 1) isolation of mitochondria from HEK cells; and 2) purification of mitoribosome-Oxa1L from mitochondria. RB: Resuspension Buffer (see Recipes) (Created with BioRender.com).

Visualizing formation of the active site in the mitochondrial ribosome.

Ribosome assembly is an essential and conserved process that is regulated at each step by specific factors. Using cryo-electron microscopy (cryo-EM), we visualize the formation of the conserved peptidyl transferase center (PTC) of the human mitochondrial ribosome. The conserved GTPase GTPBP7 regulates the correct folding of 16S ribosomal RNA (rRNA) helices and ensures 2'-O-methylation of the PTC base U3039. GTPBP7 binds the RNA methyltransferase NSUN4 and MTERF4, which sequester H68-71 of the 16S rRNA and allow biogenesis factors to access the maturing PTC. Mutations that disrupt binding of their Caenorhabditis elegans orthologs to the large subunit potently activate mitochondrial stress and cause viability, development, and sterility defects. Next-generation RNA sequencing reveals widespread gene expression changes in these mutant animals that are indicative of mitochondrial stress response activation. We also answer the long-standing question of why NSUN4, but not its enzymatic activity, is indispensable for mitochondrial protein synthesis.

Elongational stalling activates mitoribosome-associated quality control.

The human mitochondrial ribosome (mitoribosome) and associated proteins regulate the synthesis of 13 essential subunits of the oxidative phosphorylation complexes. We report the discovery of a mitoribosome-associated quality control pathway that responds to interruptions during elongation, and we present structures at 3.1- to 3.3-angstrom resolution of mitoribosomal large subunits trapped during ribosome rescue. Release factor homolog C12orf65 (mtRF-R) and RNA binding protein C6orf203 (MTRES1) eject the nascent chain and peptidyl transfer RNA (tRNA), respectively, from stalled ribosomes. Recruitment of mitoribosome biogenesis factors to these quality control intermediates suggests additional roles for these factors during mitoribosome rescue. We also report related cryo-electron microscopy structures (3.7 to 4.4 angstrom resolution) of elongating mitoribosomes bound to tRNAs, nascent polypeptides, the guanosine triphosphatase elongation factors mtEF-Tu and mtEF-G1, and the Oxa1L translocase.

Thermodynamics of voltage-gated ion channels.

Ion channels are essential for cellular signaling. Voltage-gated ion channels (VGICs) are the largest and most extensively studied superfamily of ion channels. They possess modular structural features such as voltage-sensing domains that encircle and form mechanical connections with the pore-forming domains. Such features are intimately related to their function in sensing and responding to changes in the membrane potential. In the present work, we discuss the thermodynamic mechanisms of the VGIC superfamily, including the two-state gating mechanism, sliding-rocking mechanism of the voltage sensor, subunit cooperation, lipid-infiltration mechanism of inactivation, and the relationship with their structural features.