Robust Point Cloud Registration Network for Complex Conditions.

Point cloud registration is widely used in autonomous driving, SLAM, and 3D reconstruction, and it aims to align point clouds from different viewpoints or poses under the same coordinate system. However, point cloud registration is challenging in complex situations, such as a large initial pose difference, high noise, or incomplete overlap, which will cause point cloud registration failure or mismatching. To address the shortcomings of the existing registration algorithms, this paper designed a new coarse-to-fine registration two-stage point cloud registration network, CCRNet, which utilizes an end-to-end form to perform the registration task for point clouds. The multi-scale feature extraction module, coarse registration prediction module, and fine registration prediction module designed in this paper can robustly and accurately register two point clouds without iterations. CCRNet can link the feature information between two point clouds and solve the problems of high noise and incomplete overlap by using a soft correspondence matrix. In the standard dataset ModelNet40, in cases of large initial pose difference, high noise, and incomplete overlap, the accuracy of our method, compared with the second-best popular registration algorithm, was improved by 7.0%, 7.8%, and 22.7% on the MAE, respectively. Experiments showed that our CCRNet method has advantages in registration results in a variety of complex conditions.

Phase Unwrapping Error Correction Based on Multiple Linear Regression Analysis.

Fringe projection profilometry (FPP) is prone to phase unwrapping error (PUE) due to phase noise and measurement conditions. Most of the existing PUE-correction methods detect and correct PUE on a pixel-by-pixel or partitioned block basis and do not make full use of the correlation of all information in the unwrapped phase map. In this study, a new method for detecting and correcting PUE is proposed. First, according to the low rank of the unwrapped phase map, multiple linear regression analysis is used to obtain the regression plane of the unwrapped phase, and thick PUE positions are marked on the basis of the tolerance set according to the regression plane. Then, an improved median filter is used to mark random PUE positions and finally correct marked PUE. Experimental results show that the proposed method is effective and robust. In addition, this method is progressive in the treatment of highly abrupt or discontinuous regions.

One-Pot Synthesis of Acetylacetonate-Based Isomeric Phosphorescent Cyclometalated Iridium(III) Complexes via Random Cyclometalation: A Strategy for Excited-State Manipulation.

The excited-state manipulation of the phosphorescent iridium(III) complexes plays a vital role in their photofunctional applications. The development of the molecular design strategy promotes the creative findings of novel iridium(III) complexes. The current molecular design strategies for iridium(III) complexes mainly depend on the selective cyclometalation of the ligands with the iridium(III) ion, which is governed by the steric hindrance of the ligand during the cyclometalation. Herein, a new molecular design strategy (i.e., random cyclometalation strategy) is proposed for the effective excited-state manipulation of phosphorescent cyclometalated iridium(III) complexes. Two series of new and separable methoxyl-functionalized isomeric iridium(III) complexes are accessed by a one-pot synthesis via random cyclometalation, resulting in a dramatic tuning of the phosphorescence peak wavelength (∼57 nm) and electrochemical properties attributed to the high sensitivity of their excited states to the position of the methoxyl group. These iridium(III) complexes show intense phosphorescence ranging from the yellow (567 nm) to the deep-red (634 nm) color with high photoluminescence quantum yields of up to 0.99. Two deep-red emissive iridium(III) complexes with short decay lifetimes are further utilized as triplet emitters to afford efficient solution-processed electroluminescence with reduced efficiency roll-offs.

Isomer Engineering of Lepidine-Based Iridophosphors for Far-Red Hypoxia Imaging and Photodynamic Therapy.

The development of highly efficient cyclometalated phosphorescent iridium(III) complexes is greatly promoted by their rational molecular design. Manipulating the excited states of iridophosphors could endow them with appealing photophysical properties, which play vital roles in triplet state-related photofunctional applications (e.g., electroluminescence, photodynamic therapy, etc.). In general, the most effective approach for decreasing the emission energies of iridophosphors is to extend the π-skeleton of ligands. However, the π-extension strategy often results in decreased solubility, lower synthetic yield, decreased photoluminescence quantum yield, and so forth. In this work, a simple yet efficient strategy is proposed for the effective excited-state manipulation of 2-phenyllepidine-based iridophosphors. Surprisingly, dramatic tuning of phosphorescence wavelength (∼70 nm) is achieved by simply controlling the position of a single methoxyl substituent on these iridophosphors. An oxygen-responsive iridophosphor featuring far-red emission (660 nm), long emission lifetime (1.60 µs), and high singlet oxygen quantum yield (0.73) is employed to realize accurate oxygen sensing in vitro and in vivo, and it also shows efficient photodynamic therapy in cancer cells, making it a promising candidate for the efficient image-guided photodynamic therapeutic agent. This molecular design strategy clearly demonstrates the advantages of designing novel long-wavelength emissive iridophosphors without increasing the π-conjugation of the ligand.

Mitochondria targeting fluorescent probe for MAO-A and the application in the development of drug candidate for neuroinflammation.

Monoamine oxidase A (MAO-A), as a vital drug target for various central nervous system diseases, locates in mitochondria and is mainly responsible for the oxidative inactivation of neurotransmitter amines. In the present work, a Mito-targeting fluorescent probe (HCCP) was developed to selectively and sensitively detect MAO-A activity, and successfully applied for the real-time monitoring endogenous MAO-A in living cells and tissues. Additionally, a high-throughput screening platform was established using HCCP and the inhibitory effects of 210 kinds of Herbal medicines toward MAO-A were evaluated. Evocarpine as a novel inhibitor for MAO-A was discovered from Evodia rutaecarpa, which possessed the preferred anti-neuroinflammation activity by suppressing the iNOS expression and NO production in LPS-induced BV2 cells bioactivation. In summary, HCCP was a novel Mito-targeting tool for the real-time imaging of MAO-A, provided an efficient method for real-time exploring of physiological functions of MAO-A and developing potential inhibitors of MAO-A.

Molecular photoacoustic imaging for early diagnosis and treatment monitoring of rheumatoid arthritis in a mouse model.

Rheumatoid arthritis (RA) is a progressive inflammatory joint disease. Early diagnosis is critical for timely therapeutic intervention. However, it lacks effective diagnostic methods capable of detecting disease progression in its early stage and evaluating treatment efficacy in clinics. Photoacoustic (PA) molecular imaging is a novel imaging modality that can detect in the early stage of disease and continuously monitor its progression. In this study, Evans blue (EB) was used as a PA contrast agent to detect the angiogenesis and microcirculation dysfunction in RA joint. In collagen-induced arthritis (CIA) mouse model, a distinct increase of PA signal was detected early at 2 weeks, with significant higher PA signal intensities from the RA joints compared to the normal joints. More importantly, we detected an increasing trend of PA signal intensity week by week post CIA induction, demonstrating the potential of EB-enhanced PA imaging in monitoring the development of RA. However, joint damage was silent in the X-ray at 2 weeks post CIA induction, which suggested the superiority of PA imaging in RA early detection. In addition, striking decrease of PA signal intensities in the RA joints was observed after administration with etanercept compared with the untreated RA joints. The signal changes exhibited by PA imaging were confirmed by clinical observation and histological examinations. This study demonstrated the promising use of EB-enhanced PA imaging for the early diagnosis and its feasibility for RA treatment monitoring.

Real-Time Quantification of Cartilage Degeneration by GAG-Targeted Cationic Nanoparticles for Efficient Therapeutic Monitoring in Living Mice.

One of the characterizations of degenerative cartilage disease is the progressive loss of glycosaminoglycans (GAGs). The real-time imaging method to quantify GAGs is of great significance for the biochemical analysis of cartilage and diagnosis and therapeutic monitoring of cartilage degeneration in vivo. To this end, a cationic photoacoustic (PA) contrast agent, poly-l-lysine melanin nanoparticles (PLL-MNPs), specifically targeting anionic GAGs was developed in this study to investigate whether it can image cartilage degeneration. PLL-MNP assessed GAG depletion by Chondroitinase ABC in vitro rat cartilage and intact ex vivo mouse knee joint. A papain-induced cartilage degenerative mice model was used for in vivo photoacoustic imaging (PAI). Oral cartilage supplement glucosamine sulfate was intragastrically administered for mice cartilage repair and the therapeutic efficacy was monitored by PLL-MNP-enhanced PAI. Histologic findings were used to further confirm PAI results. In vitro results revealed that the PLL-MNPs not only had a high binding ability with GAGs but also sensitively monitored GAG content changes by PAI. The PA signal was gradually weakened along with the depletion of GAGs in cartilage. Particularly, PLL-MNPs depicted the cartilage structure and the distribution of GAGs was demonstrated in PA images in ex vivo joints. Compared with the normal joint, a lower signal intensity was detected from degenerative joint at 3 weeks after papain injection, suggesting an early diagnosis of cartilage lesion by PLL-MNPs. Importantly, this PA-enhanced nanoprobe was suitable for monitoring in vivo efficacy of glucosamine sulfate, which effectively blocked cartilage degradation in a high dose manner. In vivo imaging findings correlated well with histological examinations. PLL-MNPs provided sensitive visualization of cartilage degeneration and promising monitoring of therapeutic response in living subjects.

Tracking Osteoarthritis Progress through Cationic Nanoprobe-Enhanced Photoacoustic Imaging of Cartilage.

A major obstacle in osteoarthritis (OA) theranostics is the lack of a timely and accurate monitoring method. It is hypothesized that the loss of anionic glycosaminoglycans (GAGs) in articular cartilage reflects the progression of OA. Thus, this study investigated the feasibility of photoacoustic imaging (PAI) applied for monitoring the in vivo course of OA progression via GAG-targeted cationic nanoprobes. The nanoprobes were synthesized through electrostatic attraction between poly-l-Lysine and melanin (PLL-MNPs). Cartilage explants with different concentrations of GAGs incubated with PLL-MNPs to test the relationship between GAGs content and PA signal intensity. GAG activity was then evaluated in vivo in destabilization of the medial meniscus (DMM) surgically-induced mouse model. To track OA progression over time, mice were imaged consistently for 10 weeks after OA-inducing surgery. X-ray was used to verify the superiority of PAI in detecting OA. The correlation between PAI data and histologic results was also analyzed. In vitro study demonstrated the ability of PLL-MNPs in sensitively detecting different GAGs concentrations. In vivo PAI exhibited significantly lower signal intensity from OA knees compared to normal knees. More importantly, PA signal intensity showed serial reduction over the course of OA, while X-ray showed visible joint destruction until 6 weeks. A decrease in GAGs content was confirmed by histologic examinations; moreover, histologic findings were well correlated with PAI results. Therefore, using cationic nanoprobe-enhanced PAI to detect the changes in GAG contents provides sensitive and consistent visualization of OA development. This approach will further facilitate OA theranostics and clinical translation. STATEMENT OF SIGNIFICANCE: The study of in vivo monitoring osteoarthritis (OA) is of high significance to tracking the trajectory of OA development and therapeutic monitoring. Here, we developed a cartilage-targeted cationic nanoprobe, poly-l-Lysine-melanin nanoparticles (PLL-MNPs), enhancing photoacoustic imaging (PAI) to monitor the progression of OA. The in vitro study demonstrated the ability of PLL-MNPs to detect different concentrations of GAGs with high sensitivity. We found that the contents of GAGs in vivo steadily decreased from the development of OA initial-stage to the end-point of our investigation via PAI; it reflected the course of OA in living subjects with high sensitivity. These results allow for further development in various aspects of OA research. It has potential for clinical translation and has a great impact on personalized medicine.

Nanomedicine - advantages for their use in rheumatoid arthritis theranostics.

Rheumatoid arthritis (RA) is an autoimmune disease accompanies with synovial inflammation and progressive bone destruction. Currently, anti-rheumatic drugs need high dose and frequent use for a long-term, which lead to serious side effect and low patient compliance. To overcome above problems and improve clinical efficacy, nano-technology with targeting ability, sustained release and so forth, has been proposed on RA treatment and already achieved success in RA animal models. In this review, authors summarize and illustrate representative nanomedicine targeting to RA states, which is achieved either through passive or active targeting with high affinity to the receptors that are over-expressed in macrophages or angiogenesis. In particular, authors highlight the new strategies to promote the efficacy of nanoscale treatments through phototherapy and the addition of contrast elements for theranostic application. The described advances may pave the way to better understanding and designing the novel nanomedicine and multifunctional nano-system on efficient RA treatment.

Enhancing singlet oxygen generation in semiconducting polymer nanoparticles through fluorescence resonance energy transfer for tumor treatment.

Photosensitizers (PSs) are of particular importance for efficient photodynamic therapy (PDT). Challenges for PSs simultaneously possessing strong light-absorbing ability, high 1O2 generation by effective intersystem crossing from the singlet to the triplet state, good water-solubility and excellent photostability still exist. Reported here are a new kind of dual-emissive semiconducting polymer nanoparticles (SPNs) containing fluorescent BODIPY derivatives and near-infrared (NIR) phosphorescent iridium(iii) complexes. In the SPNs, the BODIPY units serve as the energy donors in the fluorescence resonance energy transfer (FRET) process for enhancing the light absorption of the SPNs. The NIR emissive iridium(iii) complexes are chosen as the energy acceptors and efficient photosensitizers. The ionized semiconducting polymers can easily self-assemble to form hydrophilic nanoparticles and homogeneously disperse in aqueous solution. Meanwhile, the conjugated backbone of SPNs provides effective shielding for the two luminophores from photobleaching. Thus, an excellent overall performance of the SPN-based PSs has been realized and the high 1O2 yield (0.97) resulting from the synergistic effect of BODIPY units and iridium(iii) complexes through the FRET process is among the best reported for PSs. In addition, owing to the phosphorescence quenching of iridium(iii) complexes caused by 3O2, the SPNs can also be utilized for O2 mapping in vitro and in vivo, which assists in the evaluation of the PDT process and provides important instructions in early-stage cancer diagnosis.

Phosphorescent Starburst Pt(II) Porphyrins as Bifunctional Therapeutic Agents for Tumor Hypoxia Imaging and Photodynamic Therapy.

It is very meaningful to develop bifunctional therapeutic agents which can monitor the tumor hypoxia in real time as well as maintain good photodynamic therapy (PDT) effect under hypoxia. To achieve it, herein, a series of hydrophilic phosphorescent starburst Pt(II) porphyrins as bifunctional therapeutic agents for simultaneous tumor hypoxia imaging and highly efficient PDT have been rationally designed and synthesized. They have been obtained by using Pt(II) porphyrins as the functional core and cationic oligofluorenes as the arms. Such a three-dimensional structural feature ensures their hydrophilicity, ultrasensitive oxygen-sensing performance, and high 1O2 quantum yields. Furthermore, the O2-sensitive phosphorescence lifetimes of starburst Pt(II) porphyrins are beneficial to eliminate the interference from background fluorescence remarkably and enhance the signal-to-noise ratio of hypoxia imaging by using phosphorescence lifetime imaging microscopy. Their PDT effects were also evaluated both in vitro (under both hypoxia and normoxia) and in vivo. As a result, tumor hypoxia can be significantly differentiated and tumor growth can be inhibited effectively, while the systemic toxicity is not observed. All of these results demonstrate that starburst Pt(II) porphyrins could be used as the promising bifunctional therapeutic agents for early diagnosis and treatment of cancer.

Achieving efficient photodynamic therapy under both normoxia and hypoxia using cyclometalated Ru(ii) photosensitizer through type I photochemical process.

Photodynamic therapy (PDT) through the generation of singlet oxygen utilizing photosensitizers (PSs) is significantly limited under hypoxic conditions in solid tumors. So it is meaningful to develop effective PSs which can maintain excellent therapeutic effects under hypoxia. Here we reported a coumarin-modified cyclometalated Ru(ii) photosensitizer (Ru2), which exhibits lower oxidation potential and stronger absorption in the visible region than the coumarin-free counterpart. The evaluation of the PDT effect was performed under both normoxia and hypoxia. The results showed that Ru2 has a better therapeutic effect than the coumarin-free counterpart in in vitro experiments. Especially under hypoxia, Ru2 still retained an excellent PDT effect, which can be attributed to the direct charge transfer between the excited PS and an adjacent substrate through a type I photochemical process, forming highly-oxidative hydroxyl radicals to damage tumor cells. The anti-tumor activity of Ru2 was further proven to be effective in tumor-bearing mice, and tumor growth was inhibited remarkably under PDT treatment.

Targeting of interleukin (IL)-17A inhibits PDL1 expression in tumor cells and induces anticancer immunity in an estrogen receptor-negative murine model of breast cancer.

The expression of IL-17A and programmed death ligand 1 (PDL1) is increased in estrogen receptor-negative breast cancer. IL-17A promotes tumor cell survival and invasiveness and inhibits the antitumor immune response. The PDL1-PD1 (programmed death protein 1) signaling pathway promotes escape from immune surveillance in tumor cells. The pro-tumor properties of IL-17A and PDL1 in various cancers have been previously examined; however, the relationship and roles of IL-17A and PDL1 in ER-negative breast cancer have not been evaluated. Therefore, we assessed whether IL-17A promotes PDL1 expression in tumor cells and whether targeting of IL-17A could inhibit ER-negative breast cancer progression in a murine model. Our study revealed that IL-17A promoted PDL1 expression in human and mouse cells. In the murine cancer model, targeting of IL-17A inhibited PDL1 expression in the tumor microenvironment, decreased the percentage of Treg cells in tumor-infiltrating lymphocytes, and promoted CD4+ and CD8+ T cells to secrete interferon gamma. More importantly, treatment with combined anti-IL-17A and anti-PDL1 antibodies enhanced antitumor effects in favor of tumor eradication. Thus, our study established a pro-tumor role of IL-17A in promoting tumor immune escape and supports the development of a novel cytokine immunotherapy against breast cancer.

Female specific association between NNMT gene and schizophrenia in a Han Chinese population.

Accumulating evidence has shown that alterations in one carbon metabolism might play an important role in the pathogenesis of schizophrenia (SZ). Nicotinamide-N-methyltransferase (NNMT) is one of the key enzymes of one-carbon metabolism. To examine whether NNMT gene was associated with SZ in Han Chinese population, we selected seven single nucleotide polymorphisms (SNPs) in NNMT gene, and investigated its association with SZ from a cohort of 42 SZ patients and 86 healthy controls by Mass-ARRAY technology. Statistical analyses revealed that one (rs694539) of the SNPs in the female subgroup showed significant difference between SZ patients and controls both in genotypic (p= 0.0170) and allelic frequencies (p = 0.0059). We also found that the frequency of haplotype 'A G G C T C T' in the female patients was significantly higher than in controls (p=0.0015). Our results suggest that NNMT rs694539 may have a role in the etiology of SZ in a Han Chinese female population.

Mitochondrial haplogroups and hypervariable region polymorphisms in schizophrenia: a case-control study.

Previous studies have detected associations between mitochondrial haplogroups and schizophrenia (SZ). However, no study has examined the relationship between major mitochondrial DNA (mtDNA) haplogroups and SZ in the Chinese population. The aim of this study was to assess the association between mtDNA haplogroups and SZ genesis in the Chinese Han population. We used a case-control study and sequenced the mtDNA hypervariable regions (HVR1, HVR2, and HVR3) in the Han population. We analyzed mtDNA haplogroups and HVR polymorphisms in 298 SZ patients and 298 controls. The haplotypes were classified into 10 major haplogroups: A, B, CZ, D, F, G, M, N, N9a, and R. Statistical analysis revealed that only N9a showed a nominally significant association with protection from SZ [1.68% vs. 6.38%, p=0.004, OR=0.251 (0.092-0.680); after adjustment for age and sex: p=0.006, OR=0.246 (0.090-0.669)]. Three HVR polymorphisms were found to be nominally significantly different between subjects with SZ and controls, and all except one (m.204T>C) are linked to the N9a haplogroup. Our results indicate that mtDNA haplogroup N9a might be a protective factor for SZ.