Alginate oligosaccharide assimilation by gut microorganisms and the potential role in gut inflammation alleviation.

Dietary fiber metabolism by gut microorganisms plays important roles in host physiology and health. Alginate, the major dietary fiber of daily diet seaweeds, is drawing more attention because of multiple biological activities. To advance the understanding of alginate assimilation mechanism in the gut, we show the presence of unsaturated alginate oligosaccharides (uAOS)-specific alginate utilization loci (AUL) in human gut microbiome. As a representative example, a working model of the AUL from the gut microorganism Bacteroides clarus was reconstructed from biochemistry and transcriptome data. The fermentation of resulting monosaccharides through Entner-Doudoroff pathway tunes the metabolism of short-chain fatty acids and amino acids. Furthermore, we show that uAOS feeding protects the mice against dextran sulfate sodium-induced acute colitis probably by remodeling gut microbiota and metabolome. IMPORTANCE: Alginate has been included in traditional Chinese medicine and daily diet for centuries. Recently discovered biological activities suggested that alginate-derived alginate oligosaccharides (AOS) might be an active ingredient in traditional Chinese medicine, but how these AOS are metabolized in the gut and how it affects health need more information. The study on the working mechanism of alginate utilization loci (AUL) by the gut microorganism uncovers the role of unsaturated alginate oligosaccharides (uAOS) assimilation in tuning short-chain fatty acids and amino acids metabolism and demonstrates that uAOS metabolism by gut microorganisms results in a variation of cell metabolites, which potentially contributes to the physiology and health of gut.

Treatment for Resistant Hypertension Under the Guidance of Pharmacogenomics: A Randomised Controlled Open-Label Trial.

OBJECTIVE: To evaluate the efficacy and safety of pharmacogenomics (PGx)-guided treatment in individuals with resistant hypertension (RH). STUDY DESIGN: Randomised controlled open-label study. Place and Duration of the Study: Department of Cardiology, The First Hospital of China Medical University, Shenyang, Liaoning Province, China, from June 2019 to November 2021. METHODOLOGY: The study assigned RH patients to two groups. The intervention group (IG) received 12 weeks of PGx-guided treatment, while the control group (CG) followed a consensus-based approach. Examining 10 genes and their alleles with 31 antihypertensive drugs in the IG, the study provided specific medication advice. The primary outcome measured the difference in office systolic blood pressure (SBP) change from baseline at 12 weeks. Secondary outcomes included changes in diastolic blood pressure (DBP), hepatic and renal function, and major adverse cardiovascular events. RESULTS: Fifty-nine patients from the First Hospital of China Medical University participated, with 29 in the IG and 30 in the CG. Significant differences were noted in SBP reduction (IG: 31.26 ± 18.64 mmHg; CG: 14.61 ± 17.74 mmHg; p=0.001) and DBP reduction (IG: 19.61 ± 17.32 mmHg; CG: 7.81 ± 11.23 mmHg; p = 0.003) after 12 weeks. One IG patient had a heart attack, and one CG subject developed heart failure. At week 12, hepatic insufficiency was observed in one IG patient and six CG patients, while renal insufficiency occurred in five patients of both groups. CONCLUSION: Treatment guided by PGx demonstrated significant reductions in both SBP and DBP compared to consensus-based treatment. KEY WORDS: Resistant hypertension, Treatment, Pharmacogenomics, Clinical study.

Learning to Restore Compressed Point Cloud Attribute: A Fully Data-Driven Approach and A Rules-Unrolling-Based Optimization.

The emergence of holographic media drives the standardization of Geometry-based Point Cloud Compression (G-PCC) to sustain networked service provisioning. However, G-PCC inevitably introduces visually annoying artifacts, degrading the quality of experience (QoE). This work focuses on restoring G-PCC compressed point cloud attributes, e.g., RGB colors, to which fully data-driven and rules-unrolling-based post-processing filters are studied. At first, as compressed attributes exhibit nested blockiness, we develop a learning-based sample adaptive offset (NeuralSAO), which leverages a neural model using multiscale feature aggregation and embedding to characterize local correlations for quantization error compensation. Later, given statistically Gaussian distributed quantization noise, we suggest the utilization of a bilateral filter with Gaussian kernels to weigh neighbors by jointly considering their geometric and photometric contributions for restoration. Since local signals often present varying distributions, we propose estimating the smoothing parameters of the bilateral filter using an ultra-lightweight neural model. Such a bilateral filter with learnable parameters is called NeuralBF. The proposed NeuralSAO demonstrates the state-of-art restoration quality improvement, e.g., >20% BD-BR (Bjøntegaard delta rate) reduction over G-PCC on solid points clouds. However, NeuralSAO is computationally intensive and may suffer from poor generalization. On the other hand, although NeuralBF only achieves half of the gains of NeuralSAO, it is lightweight and exhibits impressive generalization across various samples. This comparative study between the data-driven large-scale NeuralSAO and the rules-unrolling-based small-scale NeuralBF helps to understand the capacity (i.e., performance, complexity, generalization) of underlying filters in terms of the quality restoration for compressed point cloud attribute.

13-oxyingenol dodecanoate derivatives induce mitophagy and ferroptosis through targeting TMBIM6 as potential anti-NSCLC agents.

Ingenol diterpenoids continue to attract the attention for their extensive biological activity and novel structural features. To further explore this type of compound as anti-tumor agent, 13-oxyingenol dodecanoate (13-OD) was prepared by a standard chemical transformation from an Euphorbia kansui extract, and 29 derivatives were synthesized through parent 13-OD. Their inhibition activities against different types of cancer were screened and some derivatives showed superior anti-non-small cell lung cancer (NSCLC) cells cytotoxic potencies than oxaliplatin. In addition, TMBIM6 was identified as a crucial cellular target of 13-OD using ABPP target angling technique, and subsequently was verified by pull down, siRNA interference, BLI and CETSA assays. With modulating the function of TMBIM6 protein by 13-OD and its derivatives, Ca2+ release function was affected, causing mitochondrial Ca2+ overload, depolarisation of membrane potential. Remarkably, 13-OD, B6, A2, and A10-2 induced mitophagy and ferroptosis. In summary, our results reveal that 13-OD, B6, A2, and A10-2 holds great potential in developing anti-tumor agents for targeting TMBIM6.

Polystyrene microplastics induce anxiety via HRAS derived PERK-NF-κB pathway.

Exposure to environmentally hazardous substances is recognized as a significant risk factor for neurological associated disorders. Among these substances, polystyrene microplastics (PS-MPs), widely utilized in various consumer products, have been reported to exhibit neurotoxicity. However, the potential association of PS-MPs with abnormal anxiety behaviors, along with the underlying molecular mechanisms and key proteins involved, remains insufficiently explored. Here, we delineated the potential mechanisms of PS-MPs-induced anxiety through proteomics and molecular investigations. We characterized the PS-MPs, observed their accumulation in the brain, leading to anxiety-like behavior in mice, which is correlated with microglia activation and pro-inflammatory response. Consistent with these findings, our studies on BV2 microglia cells showed that PS-MPs activated NF-κB-mediated inflammation resulting in the upregulation of pro-inflammatory cytokines such as TNFα and IL-1ß. Of particular significance, HRAS was identified as a key factor in the PS-MPs induced pro-inflammatory response through whole proteomics analysis, and knockdown of H-ras effectively inhibited PS-MPs induced PERK-NF-κB activation and associated pro-inflammatory response in microglia cells. Collectively, our findings highlight that PS-MPs induce anxiety of mice via the activation of the HRAS-derived PERK-NF-κB pathway in microlglia. Our results contribute valuable insights into the molecular mechanisms of PS-MPs-induced anxiety, and may offer implications for addressing neurotoxicity and prevention the adverse effects of environmentally hazardous substances, including microplastics.

Insights into the time-course cellular effects triggered by iron oxide nanoparticles by combining proteomics with the traditional pharmacology strategy.

In recent years, a number of initially approved magnetic iron oxide nanoparticle (IONP)-based nano-medicines have been withdrawn due to the obscure nano-bio effects. Therefore, there is an urgent need to study the cellular effects triggered by IONPs on cells. In this study, we investigate the time-course cellular effects on the response of RAW 264.7 cells caused by Si-IONPs via pharmacological and mass spectrometry-based proteomics techniques. Our results revealed that Si-IONPs were internalized by clathrin-mediated endocytosis within 1 hour, and gradually degraded in endolysosomes over time, which might influence autophagy, oxidative stress, innate immune response, and inflammatory response after 12 hours. Our research provides a necessary assessment of Si-IONPs for further clinical treatment.

Chemoproteomics-based profiling reveals potential antimalarial mechanism of Celastrol by disrupting spermidine and protein synthesis.

BACKGROUND: Malaria remains a global health burden, and the emergence and increasing spread of drug resistance to current antimalarials poses a major challenge to malaria control. There is an urgent need to find new drugs or strategies to alleviate this predicament. Celastrol (Cel) is an extensively studied natural bioactive compound that has shown potentially promising antimalarial activity, but its antimalarial mechanism remains largely elusive. METHODS: We first established the Plasmodium berghei ANKA-infected C57BL/6 mouse model and systematically evaluated the antimalarial effects of Cel in conjunction with in vitro culture of Plasmodium falciparum. The potential antimalarial targets of Cel were then identified using a Cel activity probe based on the activity-based protein profiling (ABPP) technology. Subsequently, the antimalarial mechanism was analyzed by integrating with proteomics and transcriptomics. The binding of Cel to the identified key target proteins was verified by a series of biochemical experiments and functional assays. RESULTS: The results of the pharmacodynamic assay showed that Cel has favorable antimalarial activity both in vivo and in vitro. The ABPP-based target profiling showed that Cel can bind to a number of proteins in the parasite. Among the 31 identified potential target proteins of Cel, PfSpdsyn and PfEGF1-α were verified to be two critical target proteins, suggesting the role of Cel in interfering with the de novo synthesis of spermidine and proteins of the parasite, thus exerting its antimalarial effects. CONCLUSIONS: In conclusion, this study reports for the first time the potential antimalarial targets and mechanism of action of Cel using the ABPP strategy. Our work not only support the expansion of Cel as a potential antimalarial agent or adjuvant, but also establishes the necessary theoretical basis for the development of potential antimalarial drugs with pentacyclic triterpenoid structures, as represented by Cel. Video Abstract.

Transcriptome and proteomic analysis of mpox virus F3L-expressing cells.

Background: Monkeypox or mpox virus (mpox) is a double-stranded DNA virus that poses a significant threat to global public health security. The F3 protein, encoded by mpox, is an apoenzyme believed to possess a double-stranded RNA-binding domain (dsRBD). However, limited research has been conducted on its function. In this study, we present data on the transcriptomics and proteomics of F3L-transfected HEK293T cells, aiming to enhance our comprehension of F3L. Methods: The gene expression profiles of pCAGGS-HA-F3L transfected HEK293T cells were analyzed using RNA-seq. Proteomics was used to identify and study proteins that interact with F3L. Real-time PCR was used to detect mRNA levels of several differentially expressed genes (DEGs) in HEK293T cells (or Vero cells) after the expression of F3 protein. Results: A total of 14,822 genes were obtained in cells by RNA-Seq and 1,672 DEGs were identified, including 1,156 up-regulated genes and 516 down-regulated genes. A total of 27 cellular proteins interacting with F3 proteins were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and 19 cellular proteins with large differences in abundance ratios were considered to be candidate cellular proteins. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that the DEGs were significantly enriched in immune-related pathways, including type I interferon signaling pathway, response to virus, RIG-I-like receptor signaling pathway, NOD-like receptor signaling pathway, etc. Moreover, some selected DEGs were further confirmed by real-time PCR and the results were consistent with the transcriptome data. Proteomics data show that cellular proteins interacting with F3 proteins are mainly related to RNA splicing and protein translation. Conclusions: Our analysis of transcriptomic and proteomic data showed that (1) F3L up-regulates the transcript levels of key genes in the innate immune signaling pathway, such as RIGI, MDA5, IRF5, IRF7, IRF9, ISG15, IFNA14, and elicits a broad spectrum of antiviral immune responses in the host. F3L also increases the expression of the FOS and JNK genes while decreasing the expression of TNFR2, these factors may ultimately induce apoptosis. (2) F3 protein interacts with host proteins involved in RNA splicing and protein translation, such as SNRNP70, POLR2H, HNRNPA1, DDX17, etc. The findings of this study shed light on the function of the F3 protein.

Single-cell transcriptome analysis uncovers underlying mechanisms of acute liver injury induced by tripterygium glycosides tablet in mice.

Tripterygium glycosides tablet (TGT), the classical commercial drug of Tripterygium wilfordii Hook. F. has been effectively used in the treatment of rheumatoid arthritis, nephrotic syndrome, leprosy, Behcet's syndrome, leprosy reaction and autoimmune hepatitis. However, due to its narrow and limited treatment window, TGT-induced organ toxicity (among which liver injury accounts for about 40% of clinical reports) has gained increasing attention. The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing (scRNA-seq) technology. The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and total bilirubin. Using the mouse model, we identified 15 specific subtypes of cells in the liver tissue, including endothelial cells, hepatocytes, cholangiocytes, and hepatic stellate cells. Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations; led to marked inflammatory response, apoptosis and fatty acid metabolism dysfunction in hepatocytes; activated hepatic stellate cells; brought about the activation, inflammation, and phagocytosis of liver capsular macrophages cells; resulted in immune dysfunction of liver lymphocytes; disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways. Thus, these findings elaborate the mechanism underlying TGT-induced acute liver injury, provide new insights into the safe and rational applications in the clinic, and complement the identification of new biomarkers and therapeutic targets for liver protection.

Systematic thermal analysis of the Arabidopsis proteome: Thermal tolerance, organization, and evolution.

Understanding the thermal stability of the plant proteome in the context of the native cellular environment would aid the design of crops with high thermal tolerance, but only limited such data are available. Here, we applied quantitative mass spectrometry to profile the thermal stability of the Arabidopsis proteome and identify thermo-sensitive and thermo-resilient protein networks in Arabidopsis, providing a basis for understanding heat-induced damage. We also show that the similarities of the protein-melting curves can be used as a proxy to evaluate system-wide protein-protein interactions in non-engineered plants and enable the identification of transient interactions exhibited by metabolons in the context of the cellular environment. Finally, we report a systematic comparison of the thermal stability of paralogs in Arabidopsis to aid the investigation and understanding of gene duplication and protein evolution. Taken together, our results could have broad implications for the fields of plant thermal tolerance, plant protein assemblies, and evolution.

Three-dimensional visualization and evaluation of hilar cholangiocarcinoma resectability and proposal of a new classification.

BACKGROUND: As digital medicine has exerted profound influences upon diagnosis and treatment of hepatobiliary diseases, our study aims to investigate the accuracy of three-dimensional visualization and evaluation (3DVE) system in assessing the resectability of hilar cholangiocarcinoma (hCCA), and explores its potential clinical value. MATERIALS AND METHODS: The discovery cohort, containing 111 patients from April 2013 to December 2019, was retrospectively included to determine resectability according to revised criteria for unresectability of hCCA. 3D visualization models were reconstructed to evaluate resectability parameters including biliary infiltration, vascular involvement, hepatic atrophy and metastasis. Evaluation accuracy were compared between contrast-enhanced CT and 3DVE. Logistic analysis was performed to identify independent risk factors of R0 resection. A new comprehensive 3DVE classification of hCCA based on factors influencing resectability was proposed to investigate its role in predicting R0 resection and prognosis. The main outcomes were also analyzed in cohort validation, including 34 patients from January 2020 to August 2022. RESULTS: 3DVE showed an accuracy rate of 91% (95%CI 83.6-95.4%) in preoperatively evaluating hCCA resectability, significantly higher than 81% (95%CI 72.8-87.7%) of that of CT (p = 0.03). By multivariable analysis, hepatic artery involvement in 3DVE was identified an independent risk factor for R1 or R2 resection (OR = 3.5, 95%CI 1.4,8.8, P < 0.01). New 3DVE hCCA classification was valuable in predicting patients' R0 resection rate (p < 0.001) and prognosis (p < 0.0001). The main outcomes were internally validated. CONCLUSIONS: 3DVE exhibited a better efficacy in evaluating hCCA resectability, compared with contrast-enhanced CT. Preoperative 3DVE demonstrated hepatic artery involvement was an independent risk factor for the absence of R0 margin. 3DVE classification of hCCA was valuable in clinical practice.

Cholesterol modulates the physiological response to nanoparticles by changing the composition of protein corona.

Nanoparticles (NPs) in biological fluids form a layer of biomolecules known as the protein corona. The protein corona has been shown to determine the biological identity and in vivo fate of NPs, but whether and how metabolites, especially disease-related small molecules, regulate the protein corona and subsequently impact NP fate in vivo is relatively poorly understood. Here we report on the effects of cholesterol on the generation of protein corona and subsequent effects. We find that high levels of cholesterol, as in hypercholesterolemia, result in a protein corona with enriched apolipoproteins and reduced complement proteins by altering the binding affinity of the proteins to the NPs. The cholesterol-mediated protein corona can induce stronger inflammatory responses to NPs in macrophages and promote the cellular uptake of NPs in hepatocytes by enhancing the recognition of lipoprotein receptors when compared with normal protein corona. The result of in vivo biodistribution assays shows that, compared with healthy mice, NPs in hypercholesterolemic mice were more likely to be delivered to the liver, spleen and brain, and less likely to be delivered to the lungs. Our findings reveal that the metabolome profile is an unexploited factor impacting the target efficacy and safety of nanomedicines, providing a way to develop personalized nanomedicines by harnessing disease-related metabolites.

Chemoproteomics reveals Sofalcone inhibits the inflammatory response of Caco-2 cells by covalently targeting HMGB1.

Sofalcone (Sof), a synthetic analog of sophoradin, is a type of natural phenol derived from the traditional medicinal herb Sophora subprostrata, with potent anti-inflammatory activity. However, the mechanisms of action of Sof for treating intestinal-associated inflammation are not well known. In this work, we identified high mobility group box 1 (HMGB1) as the key covalent target of Sof for the anti-inflammatory activity in the human colonic epithelial cells through quantitative chemoproteomics profiling.

SETD7 promotes metastasis of triple-negative breast cancer by YY1 lysine methylation.

Breast cancer has gradually become the predominant cause for cancer-associated death in women. The metastatic dissemination and underlying mechanisms of triple-negative breast cancer (TNBC) are not sufficiently understood. (Su(var)3-9, enhancer of zeste, Trithorax) domain-containing protein 7 (SETD7) is vital for promoting the metastasis of TNBC, as demonstrated in this study. Clinical outcomes were significantly worse in primary metastatic TNBC with upregulated SETD7. Overexpression of SETD7 in vitro and in vivo promotes migration of TNBC cells. Two highly conserved lysine (K) residues K173 and K411 of Yin Yang 1 (YY1) are methylated by SETD7. Further, we found that SETD7-mediated K173 residue methylation protects YY1 from the ubiquitin-proteasome degradation. Mechanistically, it was found that the SETD7/YY1 axis regulates epithelial-mesenchymal transition (EMT) and tumor cell migration via the ERK/MAPK pathway in TNBC. The findings indicated that TNBC metastasis is driven by a novel pathway, which may be a promising target for advanced TNBC treatment.

How eluents define proteomic fingerprinting of protein corona on nanoparticles.

Nanoparticles (NPs) have broad application prospects in the field of biomedicine due to their excellent physicochemical properties. When entering biological fluids, NPs inevitably encountered proteins and were subsequently surrounded by them, forming the termed protein corona (PC). As PC has been evidenced to have critical roles in deciding the biological fates of NPs, how to precisely characterize PC is vital to promote the clinical translation of nanomedicine by understanding and harnessing NPs' behaviors. During the centrifugation-based separation techniques for the PC preparation, direct elution has been most widely used to strip proteins from NPs due to its simpleness and robustness, but the roles of multifarious eluents have never been systematically declared. Herein, seven eluents composed of three denaturants, sodium dodecyl sulfate (SDS), dithiothreitol (DTT), and urea (Urea), were applied to detach PC from gold nanoparticles (AuNPs) and silica nanoparticles (SiNPs), and eluted proteins in PC have been carefully characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and chromatography coupled tandem mass spectrometry (LC-MS/MS). Our results showed that SDS and DTT were the main contributors to the efficient desorption of PC on SiNPs and AuNPs, respectively. The molecular reactions between NPs and proteins were explored and verified by SDS-PAGE analysis of PC formed in the serums pretreated with protein denaturing or alkylating agents. The proteomic fingerprinting analysis indicated the difference of the eluted proteins brought by the seven eluents was the abundance rather than the species. The enrichment of some opsonins and dysopsonins in a special elution reminds us that the possibility of biased judgments on predicting NPs' biological behaviors under different elution conditions. The synergistic effects or antagonistic effects among denaturants for eluting PC were manifested in a nanoparticle-type dependent way by integrating the properties of the eluted proteins. Collectively, this study not only underlines the urgent need of choosing the appropriate eluents for identifying PC robustly and unbiasedly, but also provides an insight into the understanding of molecular interactions during PC formation.

miR-124 mediates the expression of ccBax to regulate Cyprinid herpesvirus 2 (CyHV-2)-induced apoptosis and viral replication.

Cyprinid herpesvirus 2 (CyHV-2), the etiological agent of herpesvirus haematopoietic necrosis (HVHN) in carp and goldfish, has caused significant economic losses in the aquaculture industry. During viral infection, the host initiates a series of active or passive defences to regulate the process of virus infection. Apoptosis is a key component of active cellular defence, and members of the Bcl-2 family have been shown to play a critical role in the apoptotic process. However, the mechanism of action of the Bcl-2 family in inducing apoptosis during CyHV-2 infection remains unclear. In this study, we revealed the molecular mechanism of miRNA-mediated silver crucian carp BAX (ccBax) in CyHV-2-induced apoptosis for the first time and demonstrated that the overexpression of miR-124 suppressed ccBax expression and significantly down-regulated apoptosis in caudal fin cells of Carassius auratus gibelio (GiCF), while miR-124 inhibitors were the opposite. These studies indicated that miR-124 inhibits CyHV-2-induced apoptosis by reducing the expression of ccBax. Furthermore, the fact that transfection of miR-124 mimics promoted CyHV-2 replication, whereas miR-124 inhibitors inhibited CyHV-2 replication, indicated that miR-124 inhibited CyHV-2-induced apoptosis and contributed to viral replication. All these results suggested that miR-124 suppresses virus-induced apoptosis and promotes viral replication by targeting and regulating ccBax expression.

Advanced Strategies for Overcoming Endosomal/Lysosomal Barrier in Nanodrug Delivery.

Nanocarriers have therapeutic potential to facilitate drug delivery, including biological agents, small-molecule drugs, and nucleic acids. However, their efficiency is limited by several factors; among which, endosomal/lysosomal degradation after endocytosis is the most important. This review summarizes advanced strategies for overcoming endosomal/lysosomal barriers to efficient nanodrug delivery based on the perspective of cellular uptake and intracellular transport mechanisms. These strategies include promoting endosomal/lysosomal escape, using non-endocytic methods of delivery to directly cross the cell membrane to evade endosomes/lysosomes and making a detour pathway to evade endosomes/lysosomes. On the basis of the findings of this review, we proposed several promising strategies for overcoming endosomal/lysosomal barriers through the smarter and more efficient design of nanodrug delivery systems for future clinical applications.

Particulate Standard Establishment for Absolute Quantification of Nanoparticles by LA-ICP-MS.

The development of nanotechnology has transformed many cutting-edge studies related to single-molecule analysis into nanoparticle (NP) detection with a single-NP sensitivity and ultrahigh resolution. While laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been successful in quantifying and tracking NPs, its quantitative calibration remains a major challenge due to the lack of suitable standards and the uncertain matrix effects. Herein, we frame a new approach to prepare quantitative standards via precise synthesis of NPs, nanoscale characterization, on-demand NP distribution, and deep learning-assisted NP counting. Gold NP standards were prepared to cover the mass range from sub-femtogram to picogram levels with sufficient accuracy and precision, thus establishing an unambiguous relationship between the sampled NP number in each ablation and the corresponding mass spectral signal. Our strategy facilitated for the first time the study of the factors affecting particulate sample capture and signal transductions in LA-ICP-MS analysis and culminated in the development of an LA-ICP-MS-based method for absolute NP quantification with single-NP sensitivity and single-cell quantification capability. The achievements would herald the emergence of new frontiers cut across a spectrum of toxicological and diagnostic issues related to NP quantification.

Variational Relational Point Completion Network for Robust 3D Classification.

Real-scanned point clouds are often incomplete due to viewpoint, occlusion, and noise, which hampers 3D geometric modeling and perception. Existing point cloud completion methods tend to generate global shape skeletons and hence lack fine local details. Furthermore, they mostly learn a deterministic partial-to-complete mapping, but overlook structural relations in man-made objects. To tackle these challenges, this paper proposes a variational framework, Variational Relational point Completion network (VRCNet) with two appealing properties: 1) Probabilistic Modeling. In particular, we propose a dual-path architecture to enable principled probabilistic modeling across partial and complete clouds. One path consumes complete point clouds for reconstruction by learning a point VAE. The other path generates complete shapes for partial point clouds, whose embedded distribution is guided by distribution obtained from the reconstruction path during training. 2) Relational Enhancement. Specifically, we carefully design point self-attention kernel and point selective kernel module to exploit relational point features, which refines local shape details conditioned on the coarse completion. In addition, we contribute multi-view partial point cloud datasets (MVP and MVP-40 dataset) containing over 200,000 high-quality scans, which render partial 3D shapes from 26 uniformly distributed camera poses for each 3D CAD model. Extensive experiments demonstrate that VRCNet outperforms state-of-the-art methods on all standard point cloud completion benchmarks. Notably, VRCNet shows great generalizability and robustness on real-world point cloud scans. Moreover, we can achieve robust 3D classification for partial point clouds with the help of VRCNet, which can highly increase classification accuracy.

Advanced strategies for nucleic acids and small-molecular drugs in combined anticancer therapy.

Cancer has been considered as complex malignant consequence of genetic mutations that control the cellular proliferation, differentiation and homeostasis, thus making tumor treatment extremely challenging. To date, a variety of cargo molecules, including nucleic acids drugs (pDNA, miRNA and siRNA), therapeutic drugs (doxorubicin, paclitaxel, daunomycin and gefitinib) and imaging agents (radioisotopes, fluorescence dyes, and MRI contrast agents) have been regarded as the potential medicines in clinical application. However, non-single therapeutic drug could induce the satisfied clinical results because of tumor heterogeneity and multiple drug resistance and the nanotechnology-based combined therapy is becoming an advanced important mode for enhanced anticancer effects. The review gathers the current advanced development to co-deliver small-molecular drugs and nucleic acids for the anticancer therapy with nanomedicine-based combination. Furthermore, the superiority is definitely presented and the barriers are detail discussed to surmount the clinical challenges. In final, future perspectives in rational direction for combined tumor therapy of drugs and nucleic acids are exhibited.