Self-Supervised 3D Scene Flow Estimation and Motion Prediction using Local Rigidity Prior.

In this article, we investigate self-supervised 3D scene flow estimation and class-agnostic motion prediction on point clouds. A realistic scene can be well modeled as a collection of rigidly moving parts, therefore its scene flow can be represented as a combination of rigid motion of these individual parts. Building upon this observation, we propose to generate pseudo scene flow labels for self-supervised learning through piecewise rigid motion estimation, in which the source point cloud is decomposed into local regions and each region is treated as rigid. By rigidly aligning each region with its potential counterpart in the target point cloud, we obtain a region-specific rigid transformation to generate its pseudo flow labels. To mitigate the impact of potential outliers on label generation, when solving the rigid registration for each region, we alternately perform three steps: establishing point correspondences, measuring the confidence for the correspondences, and updating the rigid transformation based on the correspondences and their confidence. As a result, confident correspondences will dominate label generation, and a validity mask will be derived for the generated pseudo labels. By using the pseudo labels together with their validity mask for supervision, models can be trained in a self-supervised manner. Extensive experiments on FlyingThings3D and KITTI datasets demonstrate that our method achieves new state-of-the-art performance in self-supervised scene flow learning, without any ground truth scene flow for supervision, even performing better than some supervised counterparts. Additionally, our method is further extended to class-agnostic motion prediction and significantly outperforms previous state-of-the-art self-supervised methods on nuScenes dataset.

Comparing the pharmacological effects of the prepared folium of Epimedium brevicornu Maxim. and Epimedium sagittatum Maxim. on kidney-Yang deficiency syndrome and liver injury complications.

Yinyanghuo, a famous herb, includes the folium of Epimedium brevicornu Maxim. and Epimedium sagittatum Maxim. It is believed that their processed products, the prepared slices of the folium of Epimedium brevicornu Maxim. (PFEB) and Epimedium sagittatum Maxim. (PFES) have greater efficacy in tonifying kidney Yang to treat kidney-Yang deficiency syndrome (KDS). However, there are few studies comparing the pharmacological effects of PFEB and PFES, and the underlying mechanisms. This study compared their effects on improving hypothalamic-pituitary-adrenal (HPA) axis, immune system and sexual characteristic, as well as repairing liver injury complications in the KDS model mice. Additionally, the mechanisms of the effects relevance to their main components were explored. It was found that PFEB was more effective than PFES in increasing cAMP/cGMP ratio, SOD activity, CRH and ACTH levels, eNOS and testosterone levels, splenic lymphocytes proliferation, while in decreasing MDA content, atrophy of spleen and thymus, splenic lymphocytes apoptosis, and PDE5 level. PFES showed stronger protection than PFEB in decreasing triglyceride and hepatic lipid. The contents of baohuoside I and epimedin A, B were much higher in PFEB, while Epimedin C, Icariin, 2-O″-rhamnosylicaridide II were higher in PFES. Consequently, PFEB exhibits superior efficacy over PFES in tonifying the kidney-Yang by improving the neuroendocrine-immune network, including HPA axis, immune systems, and corpus cavernosum. However, PFES has better recovery effect on mild hepatic lipid caused by KDS. The efficacy difference between PFEB and PFES in kidney-Yang and liver may be attributed to the content variations of baohuoside I.

Nucleoporin 93 Regulates Cancer Cell Growth and Stemness in Bladder Cancer via Wnt/ß-Catenin Signaling.

Bladder cancer (BLCA) is a prevalent cancer type with an unmet need for new therapeutic strategies. Nucleoporin 93 (Nup93) is implicated in the pathophysiology of several cancers, but its relationship with bladder cancer remains unclear. Nup93 expression was analyzed in TCGA datasets and 88 BLCA patient samples. Survival analysis and Cox regression models evaluated the association between Nup93 levels and patient prognosis. BLCA cells were used to investigate the effects of Nup93 overexpression or knockdown on cell growth, invasion, stemness (sphere formation and ALDH2 + cancer stem cell marker), and Wnt/ß-catenin signaling in vitro. The Wnt activator BML-284 was used to confirm the involvement of Wnt/ß-catenin signaling pathway. A xenograft mouse model validated the in vitro findings. Nup93 was highly expressed in BLCA tissues and cell lines, and high Nup93 expression correlated with poor prognosis in BLCA patients. Nup93 silencing inhibited BLCA cell proliferation, Wnt/ß-catenin activation, and cancer cell stemness. Conversely, Nup93 overexpression promoted these effects. BML-284 partially rescued the reduction in cell growth and stemness markers caused by Nup93 knockdown. Nup93 knockdown also suppressed the tumor formation of BLCA cells in vivo. Nup93 regulates BLCA cell growth and stemness via the Wnt/ß-catenin pathway, suggesting its potential as a prognostic marker and therapeutic target in BLCA.

Inflammatory corpuscle AIM2 facilitates macrophage foam cell formation by inhibiting cholesterol efflux protein ABCA1.

The inflammatory corpuscle recombinant absents in melanoma 2 (AIM2) and cholesterol efflux protein ATP binding cassette transporter A1(ABCA1) have been reported to play opposing roles in atherosclerosis (AS) plaques. However, the relationship between AIM2 and ABCA1 remains unclear. In this study, we explored the potential connection between AIM2 and ABCA1 in the modulation of AS by bioinformatic analysis combined with in vitro experiments. The GEO database was used to obtain AS transcriptional profiling data; screen differentially expressed genes (DEGs) and construct a weighted gene co-expression network analysis (WGCNA) to obtain AS-related modules. Phorbol myristate acetate (PMA) was used to induce macrophage modelling in THP-1 cells, and ox-LDL was used to induce macrophage foam cell formation. The experiment was divided into Negative Control (NC) group, Model Control (MC) group, AIM2 overexpression + ox-LDL (OE AIM2 + ox-LDL) group, and AIM2 short hairpin RNA + ox-LDL (sh AIM2 + ox-LDL) group. The intracellular cholesterol efflux rate was detected by scintillation counting; high-performance liquid chromatography (HPLC) was used to detect intracellular cholesterol levels; apoptosis levels were detected by TUNEL kit; levels of inflammatory markers (IL-1ß, IL-18, ROS, and GSH) were detected by ELISA kits; and levels of AIM2 and ABCA1 proteins were detected by Western blot. Bioinformatic analysis revealed that the turquoise module correlated most strongly with AS, and AIM2 and ABCA1 were co-expressed in the turquoise module with a trend towards negative correlation. In vitro experiments demonstrated that AIM2 inhibited macrophage cholesterol efflux, resulting in increased intracellular cholesterol levels and foam cell formation. Moreover, AIM2 had a synergistic effect with ox-LDL, exacerbating macrophage oxidative stress and inflammatory response. Silencing AIM2 ameliorated the above conditions. Furthermore, the protein expression levels of AIM2 and ABCA1 were consistent with the bioinformatic analysis, showing a negative correlation. AIM2 inhibits ABCA1 expression, causing abnormal cholesterol metabolism in macrophages and ultimately leading to foam cell formation. Inhibiting AIM2 may reverse this process. Overall, our study suggests that AIM2 is a reliable anti-inflammatory therapeutic target for AS. Inhibiting AIM2 expression may reduce foam cell formation and, consequently, inhibit the progression of AS plaques.

Distribution patterns, risk assessment and potential sources of heavy metals in sediment in the Qiongzhou Strait, China.

Risk assessment and pollutant source analysis are crucial tools for the management and protection of coastal ecosystems. The distribution patterns, risk assessment, and potential sources of heavy metals (Cd, Cr, Fe, Ni, Cu, Zn, As, Hg, and Pb) in surface sediment were analyzed in the Qiongzhou Strait, China, in summer and autumn of 2022. Heavy metals in autumn showed higher ecological risk than that in summer. Seasonal shifts in ocean currents may result in variations in heavy metal accumulation and dispersion. Cd and Hg were the priority heavy metals found, and according to the Positive Matrix Factorization results, the study area contains five sources of pollution, with natural sources, shipping-related activities, and industrial activities being the primary contributors. This study indicated that pollutants from adjacent areas should be considered for managing the environmental quality of Qiongzhou Strait.

The Single Cell Immunogenomic Landscape after Neoadjuvant Immunotherapy combined Chemotherapy in Esophageal Squamous Cell Carcinoma.

Neoadjuvant immunotherapy represents promising strategy in the treatment of esophageal squamous cell carcinoma (ESCC). However, the mechanisms underlying its impact on treatment sensitivity or resistance remain a subject of controversy. In this study, we conducted single-cell RNA and T/B cell receptor (scTCR/scBCR) sequencing of CD45+ immune cells on samples from 10 patients who received neoadjuvant immunotherapy and chemotherapy. We also validated our findings using multiplexed immunofluorescence and analyzed bulk RNA-seq from other cohorts in public database. By integrating analysis of 87357 CD45+ cells, we found GZMK+ effector memory T cells were relatively enriched and CXCL13+ exhausted T cells and regulator T cells decreased among responders, indicating a persistent anti-tumor memory process. Additionally, the enhanced presence of BCR expansion and somatic hypermutation process within TNFRSF13B+ memory B cells suggested their roles in antigen presentation. This was further corroborated by the evidence of the T-B co-stimulation pattern and CXCL13-CXCR5 axis. The complexity of myeloid cell heterogeneity was also particularly pronounced. The elevated expression of S100A7 in ESCC, as detected by bulk RNA-seq, was associated with an exhausted and immunosuppressive tumor microenvironment. In summary, this study has unveiled a potential regulatory network among immune cells and the clonal dynamics of their functions, and the mechanisms of exhaustion and memory conversion between GZMK+ Tem and TNFRSF13B+ Bmem from antigen presentation and co-stimulation perspectives during neoadjuvant PD-1 blockade treatment in ESCC.

Using Surface Composition and Energy to Control the Formation of Either Tetrahexahedral or Hexoctahedral High-Index Facet Nanostructures.

High-index facet nanoparticles with structurally complex shapes, such as tetrahexahedron (THH) and hexoctahedron (HOH), represent a class of materials that are important for catalysis, and the study of them provides a fundamental understanding of the relationship between surface structures and catalytic properties. However, the high surface energies render them thermodynamically unfavorable compared to low-index facets, thereby making their syntheses challenging. Herein, we report a method to control the shape of high-index facet Cu nanoparticles (either THH with {210} facets or HOH with {421} facets) by tuning the facet surface energy with trace amounts of Te atoms. Density functional theory (DFT) calculations reveal that the density of Te atoms on Cu nanoparticles can change the relative stability of the high-index facets associated with either the THH or HOH structures. By controlling the annealing conditions and the rate of Te dealloying from CuTe nanoparticles, the surface density of Te atoms can be deliberately adjusted, which can be used to force the formation of either THH (higher surface Te density) or HOH (lower surface Te density) nanoparticles.

Immune cells mediated the causal relationship between the gut microbiota and lung cancer: a Mendelian randomization study.

Introduction: The gut microbiota (GM) influences the occurrence and progression of lung cancer (LC), with potential involvement of immune cells (IC). We aimed to investigate the causal impact of GM on LC and identify potential immune cell mediators. Methods: The utilized data for the Genome-Wide Association Studies (GWAS) were summarized as follows: gut microbiota data from the Dutch Microbiome Project (DMP) (N = 7,738), lung cancer data from the Transdisciplinary Research in Cancer of the Lung (TRICL) and International Lung Cancer Consortium (ILCCO) (Ncase = 29,266, Ncontrol = 56,450) included four types of cancer: NSCLC, LUAD, LUSC, and SCLC, and immune cell data from European populations (N = 3,757). We employed bi-directional two-sample univariable Mendelian randomization (UVMR), multivariable Mendelian randomization (MVMR), and mediation analysis to assess the causal relationship between GM and LC and potential immune cell mediators. Results: Bi-directional UVMR analysis revealed that 24 gut microbiota species can affect LC, while LC can affect the abundance of 17 gut microbiota species. Mediation analysis demonstrated that six immune cells mediated the causal relationships of seven gut microbiota species on LC: "CCR7 on naive CD8+ T cell" mediated the causal relationship between s_Alistipes_putredinis and LUAD, with a mediation proportion of 9.5% and P = 0.018; "IgD- CD27- B cell %lymphocyte" mediated the causal relationships between g_Gordonibacter and s_Gordonibacter_pamelaeae with LUSC, with mediation proportions of 11.8% and 11.9%, respectively and P = 0.029; "CD20- CD38- B cell %lymphocyte" mediated the causal relationship between s_Bacteroides_clarus and SCLC, with a mediation proportion of 13.8% and P = 0.005; "CD20 on IgD+ CD38- unswitched memory B cell" mediated the causal relationship between s_Streptococcus_thermophilus and SCLC, with a mediation proportion of 14.1% and P = 0.023; "HLA DR on CD14- CD16+ monocyte" mediated the causal relationship between s_Bifidobacterium_bifidum and SCLC, with a mediation proportion of 8.7% and P = 0.012; "CD45 on Granulocytic Myeloid-Derived Suppressor Cells" mediated the causal relationship between f_Lactobacillaceae and SCLC, with a mediation proportion of 4.0% and P = 0.021. Conclusion: This Mendelian randomization study identified several specific gut microbiotas that exhibit causal relationships with lung cancer and potentially mediate immune cells.

Experimental validation of the accuracy of robotic-assisted radioactive seed implantation for tumor treatment.

An experimental validation of a robotic system for radioactive iodine-125 seed implantation (RISI) in tumor treatment was conducted using customized phantom models and animal models simulating liver and lung lesions. The robotic system, consisting of planning, navigation, and implantation modules, was employed to implant dummy radioactive seeds into the models. Fiducial markers were used for target localization. In phantom experiments across 40 cases, the mean errors between planned and actual seed positions were 0.98 ± 1.05 mm, 1.14 ± 0.62 mm, and 0.90 ± 1.05 mm in the x, y, and z directions, respectively. The x, y, and z directions correspond to the left-right, anterior-posterior, and superior-inferior anatomical planes. Silicone phantoms exhibiting significantly smaller x-axis errors compared to liver and lung phantoms (p < 0.05). Template assistance significantly reduced errors in all axes (p < 0.05). No significant dosimetric deviations were observed in parameters such as D90, V100, and V150 between plans and post-implant doses (p > 0.05). In animal experiments across 23 liver and lung cases, the mean implantation errors were 1.28 ± 0.77 mm, 1.66 ± 0.69 mm, and 1.86 ± 0.93 mm in the x, y, and z directions, slightly higher than in phantoms (p < 0.05), with no significant differences between liver and lung models. The dosimetric results closely matched planned values, confirming the accuracy of the robotic system for RISI, offering new possibilities in clinical tumor treatment.

Introduction of the difluoromethyl group at the meta- or para-position of pyridines through regioselectivity switch.

Difluoromethyl pyridines have gained significant attention in medicinal and agricultural chemistry. The direct C-H-difluoromethylation of pyridines represents a highly efficient economic way to access these azines. However, the direct meta-difluoromethylation of pyridines has remained elusive and methods for site-switchable regioselective meta- and para-difluoromethylation are unknown. Here, we demonstrate the meta-C-H-difluoromethylation of pyridines through a radical process by using oxazino pyridine intermediates, which are easily accessed from pyridines. The selectivity can be readily switched to para by in situ transformation of the oxazino pyridines to pyridinium salts upon acid treatment. The preparation of various meta- and para-difluoromethylated pyridines through this approach is presented. The mild conditions used also allow for the late-stage meta- or para-difluoromethylation of pyridine containing drugs. Sequential double functionalization of pyridines is presented, which further underlines the value of this work.

The Effects of Ketogenic Diet on Brain Gene Expressions in Type 2 Diabetes Background.

Type 2 diabetes mellitus (T2DM) is a major risk factor of a number of neurodegenerative diseases (NDDs). Ketogenic diet (KD) has significant beneficial effects on glycemic control and may act effectively against NDDs, but the mechanism remains unclear. In this study, we aimed to investigate the potential effects of KD on gene expressions in the brains of T2DM model mice. Male db/db mice at the age of 9 weeks were fed with KD or normal diet to the age of 6 months, and the whole brains were subjected to mRNA-seq analysis for differentially expressed genes. KD significantly lowered fasting glucose and body weights in db/db mice (P < 0.05), and the expression of 189 genes in the brain were significantly changed (P < 0.05, |log2| > 1). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that the differentially expressed genes upon KD are involved in inflammatory responses and the functions of biosynthesis. In inflammatory responses, NF-κB signaling pathway, viral protein interaction with cytokine and cytokine receptor, and cytokine-cytokine receptor interaction pathways were enriched, and in biosynthesis pathways, genes functioning in lipid and amino acid metabolism, protein synthesis, and energy metabolism were enriched. Moreover, consistent with the gene set enrichment analysis results, proteasomal activity measured biochemically were enhanced in KD-fed T2DM mice. These data may facilitate the understanding of how KD can be protective to the brain in T2DM background. KD could be a new strategy for the prevention of NDDs in T2DM patients.

Determinants of mosaic chromosomal alteration fitness.

Clonal hematopoiesis (CH) is characterized by the acquisition of a somatic mutation in a hematopoietic stem cell that results in a clonal expansion. These driver mutations can be single nucleotide variants in cancer driver genes or larger structural rearrangements called mosaic chromosomal alterations (mCAs). The factors that influence the variations in mCA fitness and ultimately result in different clonal expansion rates are not well understood. We used the Passenger-Approximated Clonal Expansion Rate (PACER) method to estimate clonal expansion rate as PACER scores for 6,381 individuals in the NHLBI TOPMed cohort with gain, loss, and copy-neutral loss of heterozygosity mCAs. Our mCA fitness estimates, derived by aggregating per-individual PACER scores, were correlated (R2 = 0.49) with an alternative approach that estimated fitness of mCAs in the UK Biobank using population-level distributions of clonal fraction. Among individuals with JAK2 V617F clonal hematopoiesis of indeterminate potential or mCAs affecting the JAK2 gene on chromosome 9, PACER score was strongly correlated with erythrocyte count. In a cross-sectional analysis, genome-wide association study of estimates of mCA expansion rate identified a TCL1A locus variant associated with mCA clonal expansion rate, with suggestive variants in NRIP1 and TERT.

Advancements in Solid-State Hydrogen Storage: A Review on the Glass Microspheres.

Glass microspheres, with their unique internal structure and chemical stability, offer a promising solution for the challenges of hydrogen storage and transmission, potentially advancing the utility of hydrogen as a safe and efficient energy source. In this review, we systematically evaluate various treatment and modification strategies, including fusion, sol-gel, and chemical vapor deposition (CVD), and compare the performance of different types of glass microspheres. Our synthesis of current research findings reveals that specific low-cost and environmentally friendly modification techniques can significantly enhance the hydrogen storage efficiency of glass microspheres, with some methods increasing storage capacity by up to 32% under certain conditions. Through a detailed life-cycle and cost-benefit assessment, our study highlights the economic and sustainability advantages of using modified glass microspheres. For example, selected alternative materials used in lightweight vehicles have been shown to reduce density by approximately 10% while reducing costs. This review not only underscores the contributions of modified glass microspheres to overcoming the limitations of current hydrogen storage technologies but also provides a systematic framework for improving their performance in hydrogen storage applications. Our research suggests that modified glass microspheres could help to make hydrogen energy more commercially viable and environmentally friendly.

Deep Red Light Driven Hydrogen Evolution by Heterojunction Polymer Dots for Diabetic Wound Healing.

We describe small heterojunction polymer dots (Pdots) with deep-red light catalyzed H2 generation for diabetic skin wound healing. The Pdots with donor/acceptor heterojunctions showed remarkably enhanced photocatalytic activity as compared to the donor or acceptor nanoparticles alone. We encapsulate the Pdots and ascorbic acid into liposomes to form Lipo-Pdots nanoreactors, which selectively scavenge •OH radicals in live cells and tissues under 650 nm light illumination. The antioxidant capacity of the heterojunction Pdots is ~10 times higher than that of the single-component Pdots described previously. Under a total light dose of 360 J/cm2, the Lipo-Pdots nanoreactors effectively scavenged •OH radicals and suppressed the expression of pro-inflammatory cytokines in skin tissues, thereby accelerating the healing of skin wounds in diabetic mice. This study provides a feasible solution for safe and effective treatment of diabetic foot ulcers.

GhTKPR1_8 functions to inhibit anther dehiscence and reduce pollen viability in cotton.

Sporopollenin, as the main component of the pollen exine, is a highly resistant polymer that provides structural integrity under unfavourable environmental conditions. Tetraketone α-pyrone reductase 1 (TKPR1) is essential for sporopollenin formation, catalyzing the reduction of tetraketone carbonyl to hydroxylated α-pyrone. The functional role of TKPR1 in male sterility has been reported in flowering plants such as maize, rice, and Arabidopsis. However, the molecular cloning and functional characterization of TKPR1 in cotton remain unaddressed. In this study, we identified 68 TKPR1s from four cotton species, categorized into three clades. Transcriptomics and RT-qPCR demonstrated that GhTKPR1_8 exhibited typical expression patterns in the tetrad stage of the anther. GhTKPR1_8 was localized to the endoplasmic reticulum. Moreover, ABORTED MICROSPORES (GhAMS) transcriptionally activated GhTKPR1_8 as indicated by luciferase complementation tests. GhTKPR1_8-knockdown inhibited anther dehiscence and reduced pollen viability in cotton. Additionally, overexpression of GhTKPR1_8 in the attkpr1 mutant restored its male sterile phenotype. This study offers novel insights into the investigation of TKPR1 in cotton while providing genetic resources for studying male sterility.

Subtype-WGME enables whole-genome-wide multi-omics cancer subtyping.

We present an innovative strategy for integrating whole-genome-wide multi-omics data, which facilitates adaptive amalgamation by leveraging hidden layer features derived from high-dimensional omics data through a multi-task encoder. Empirical evaluations on eight benchmark cancer datasets substantiated that our proposed framework outstripped the comparative algorithms in cancer subtyping, delivering superior subtyping outcomes. Building upon these subtyping results, we establish a robust pipeline for identifying whole-genome-wide biomarkers, unearthing 195 significant biomarkers. Furthermore, we conduct an exhaustive analysis to assess the importance of each omic and non-coding region features at the whole-genome-wide level during cancer subtyping. Our investigation shows that both omics and non-coding region features substantially impact cancer development and survival prognosis. This study emphasizes the potential and practical implications of integrating genome-wide data in cancer research, demonstrating the potency of comprehensive genomic characterization. Additionally, our findings offer insightful perspectives for multi-omics analysis employing deep learning methodologies.

Risk assessment model based on nucleotide metabolism-related genes highlights SLC27A2 as a potential therapeutic target in breast cancer.

PURPOSE: Breast cancer (BC) is the most prevalent malignant tumor worldwide among women, with the highest incidence rate. The mechanisms underlying nucleotide metabolism on biological functions in BC remain incompletely elucidated. MATERIALS AND METHODS: We harnessed differentially expressed nucleotide metabolism-related genes from The Cancer Genome Atlas-BRCA, constructing a prognostic risk model through univariate Cox regression and LASSO regression analyses. A validation set and the GSE7390 dataset were used to validate the risk model. Clinical relevance, survival and prognosis, immune infiltration, functional enrichment, and drug sensitivity analyses were conducted. RESULTS: Our findings identified four signature genes (DCTPP1, IFNG, SLC27A2, and MYH3) as nucleotide metabolism-related prognostic genes. Subsequently, patients were stratified into high- and low-risk groups, revealing the risk model's independence as a prognostic factor. Nomogram calibration underscored superior prediction accuracy. Gene Set Variation Analysis (GSVA) uncovered activated pathways in low-risk cohorts and mobilized pathways in high-risk cohorts. Distinctions in immune cells were noted between risk cohorts. Subsequent experiments validated that reducing SLC27A2 expression in BC cell lines or using the SLC27A2 inhibitor, Lipofermata, effectively inhibited tumor growth. CONCLUSIONS: We pinpointed four nucleotide metabolism-related prognostic genes, demonstrating promising accuracy as a risk prediction tool for patients with BC. SLC27A2 appears to be a potential therapeutic target for BC among these genes.