SpecEncoder: deep metric learning for accurate peptide identification in proteomics.

MOTIVATION: Tandem mass spectrometry (MS/MS) is a crucial technology for large-scale proteomic analysis. The protein database search or the spectral library search are commonly used for peptide identification from MS/MS spectra, which, however, may face challenges due to experimental variations between replicated spectra and similar fragmentation patterns among distinct peptides. To address this challenge, we present SpecEncoder, a deep metric learning approach to address these challenges by transforming MS/MS spectra into robust and sensitive embedding vectors in a latent space. The SpecEncoder model can also embed predicted MS/MS spectra of peptides, enabling a hybrid search approach that combines spectral library and protein database searches for peptide identification. RESULTS: We evaluated SpecEncoder on three large human proteomics datasets, and the results showed a consistent improvement in peptide identification. For spectral library search, SpecEncoder identifies 1%-2% more unique peptides (and PSMs) than SpectraST. For protein database search, it identifies 6%-15% more unique peptides than MSGF+ enhanced by Percolator, Furthermore, SpecEncoder identified 6%-12% additional unique peptides when utilizing a combined library of experimental and predicted spectra. SpecEncoder can also identify more peptides when compared to deep-learning enhanced methods (MSFragger boosted by MSBooster). These results demonstrate SpecEncoder's potential to enhance peptide identification for proteomic data analyses. AVAILABILITY AND IMPLEMENTATION: The source code and scripts for SpecEncoder and peptide identification are available on GitHub at https://github.com/lkytal/SpecEncoder. Contact: hatang@iu.edu.

Blocking CXCR4-CARM1-YAP axis overcomes osteosarcoma doxorubicin resistance by suppressing aerobic glycolysis.

Osteosarcoma, recognized for its aggressiveness and resistance to chemotherapy, notably doxorubicin, poses significant treatment challenges. This comprehensive study investigated the CXCR4-CARM1-YAP signaling axis and its pivotal function in controlling aerobic glycolysis, which plays a crucial role in doxorubicin resistance. Detailed analysis of Dox-resistant 143b/MG63-DoxR cells has uncovered the overexpression of CXCR4. Utilizing a combination of molecular biology techniques including gene silencing, aerobic glycolysis assays such as Seahorse experiments, RNA sequencing, and immunofluorescence staining. The study provides insight into the mechanistic pathways involved. Results demonstrated that disrupting CXCR4 expression sensitizes cells to doxorubicin-induced apoptosis and alters glycolytic activity. Further RNA sequencing revealed that CARM1 modulated this effect through its influence on glycolysis, with immunofluorescence of clinical samples confirming the overexpression of CXCR4 and CARM1 in drug-resistant tumors. Chromatin immunoprecipitation studies further highlighted the role of CARM1, showing it to be regulated by methylation at the H3R17 site, which in turn affected YAP expression. Crucially, in vivo experiments illustrated that CARM1 overexpression could counteract the tumor growth suppression that resulted from CXCR4 inhibition. These insights revealed the intricate mechanisms at play in osteosarcoma resistance to doxorubicin and pointed toward potential new therapeutic strategies that could target this metabolic and signaling network to overcome drug resistance and improve patient outcomes.

DNMT3B activates FGFR3-mediated endoplasmic reticulum stress by regulating PTPN2 promoter methylation to promote the development of atherosclerosis.

Endoplasmic reticulum (ER) stress is closely associated with atherosclerosis (AS). Nevertheless, the regulatory mechanism of ER stress in endothelial cells during AS progression is unclear. Here, the role and regulatory mechanism of DNA (cytosine-5-)- methyltransferase 3 beta (DNMT3B) in ER stress during AS progression were investigated. ApoE-/- mice were fed with high fat diet to construct AS model in vivo. HE and Masson staining were performed to analyze histopathological changes and collagen deposition. HUVECs stimulated by ox-LDL were used as AS cellular model. Cell apoptosis was examined using flow cytometry. DCFH-DA staining was performed to examine ROS level. The levels of pro-inflammatory cytokines were assessed using ELISA. In addition, MSP was employed to detect PTPN2 promoter methylation level. Our results revealed that DNMT3B and FGFR3 were significantly upregulated in AS patient tissues, whereas PTPN2 was downregulated. PTPN2 overexpression attenuate ox-LDL-induced ER stress, inflammation and apoptosis in HUVECs and ameliorated AS symptoms in vivo. PTPN2 could suppress FGFR3 expression in ox-LDL-treated HUVECs, and FGFR3 knockdown inhibited ER stress to attenuate ox-LDL-induced endothelial cell apoptosis. DNMT3B could negatively regulate PTPN2 expression and positively FGFR2 expression in ox-LDL-treated HUVECs; DNMT3B activated FGFR2 expression by increasing PTPN2 promoter methylation level. DNMT3B downregulation repressed ox-LDL-induced ER stress, inflammation and cell apoptosis in endothelial cells, which was reversed by PTPN2 silencing. DNMT3B activated FGFR3-mediated ER stress by increasing PTPN2 promoter methylation level and suppressed its expression, thereby boosting ER stress to facilitate AS progression.

Pimpinellin ameliorates macrophage inflammation by promoting RNF146-mediated PARP1 ubiquitination.

Macrophage inflammation plays a central role during the development and progression of sepsis, while the regulation of macrophages by parthanatos has been recently identified as a novel strategy for anti-inflammatory therapies. This study was designed to investigate the therapeutic potential and mechanism of pimpinellin against LPS-induced sepsis. PARP1 and PAR activation were detected by western blot or immunohistochemistry. Cell death was assessed by flow cytometry and western blot. Cell metabolism was measured with a Seahorse XFe24 extracellular flux analyzer. C57, PARP1 knockout, and PARP1 conditional knock-in mice were used in a model of sepsis caused by LPS to assess the effect of pimpinellin. Here, we found that pimpinellin can specifically inhibit LPS-induced macrophage PARP1 and PAR activation. In vitro studies showed that pimpinellin could inhibit the expression of inflammatory cytokines and signal pathway activation in macrophages by inhibiting overexpression of PARP1. In addition, pimpinellin increased the survival rate of LPS-treated mice, thereby preventing LPS-induced sepsis. Further research confirmed that LPS-induced sepsis in PARP1 overexpressing mice was attenuated by pimpinellin, and PARP1 knockdown abolished the protective effect of pimpinellin against LPS-induced sepsis. Further study found that pimpinellin can promote ubiquitin-mediated degradation of PARP1 through RNF146. This is the first study to demonstrate that pimpinellin inhibits excessive inflammatory responses by promoting the ubiquitin-mediated degradation of PARP1.

Myricanol attenuates sepsis-induced inflammatory responses by nuclear factor erythroid 2-related factor 2 signaling and nuclear factor kappa B/mitogen-activated protein kinase pathway via upregulating Sirtuin 1.

Sepsis, a life-threatening condition characterized by dysregulated immune responses, remains a significant clinical challenge. Myricanol, a natural compound, plays a variety of roles in regulating lipid metabolism, anti-cancer, anti-neurodegeneration, and it could act as an Sirtuin 1 (SIRT1) activator. This study aimed to explore the therapeutic potential and underlying mechanism of myricanol in the lipopolysaccharide (LPS)-induced sepsis model. In vivo studies revealed that myricanol administration significantly improved the survival rate of LPS-treated mice, effectively mitigating LPS-induced inflammatory responses in lung tissue. Furthermore, in vitro studies demonstrated that myricanol treatment inhibited the expression of pro-inflammatory cytokines, attenuated signal pathway activation, and reduced oxidative stress in macrophages. In addition, we demonstrated that myricanol selectively enhances SIRT1 activation in LPS-stimulated macrophages, and all of the protective effect of myricanol were reversed through SIRT1 silencing. Remarkably, the beneficial effects of myricanol against LPS-induced sepsis were abolished in SIRT1 myeloid-specific knockout mice, underpinning the critical role of SIRT1 in mediating myricanol's therapeutic efficacy. In summary, this study provides significant evidence that myricanol acts as a potent SIRT1 activator, targeting inflammatory signal pathways and oxidative stress to suppress excessive inflammatory responses. Our findings highlight the potential of myricanol as a novel therapeutic agent for the treatment of LPS-induced sepsis.

State-dependent memory retrieval: insights from neural dynamics and behavioral perspectives.

Memory retrieval is strikingly susceptible to external states (environment) and internal states (mood states and alcohol), yet we know little about the underlying mechanisms. We examined how internally generated states influence successful memory retrieval using the functional magnetic resonance imaging (fMRI) of laboratory mice during memory retrieval. Mice exhibited a strong tendency to perform memory retrieval correctly only in the reinstated mammillary body-inhibited state, in which mice were trained to discriminate auditory stimuli in go/no-go tasks. fMRI revealed that distinct auditory cues engaged differential brain regions, which were primed by internal state. Specifically, a cue associated with a reward activated the lateral amygdala, while a cue signaling no reward predominantly activated the postsubiculum. Modifying these internal states significantly altered the neural activity balance between these regions. Optogenetic inhibition of those regions in the precue period blocked the retrieval of type-specific memories. Our findings suggest that memory retrieval is under the control of two interrelated neural circuits underlying the neural basis of state-dependent memory retrieval.

Chronic remote ischemic conditioning treatment in patients with chronic stable angina (EARLY-MYO-CSA): a randomized, controlled proof-of-concept trial.

BACKGROUND: Chronic remote ischemic conditioning (CRIC) has been shown to improve myocardial ischemia in experimental animal studies; however, its effectiveness in patients with chronic stable angina (CSA) has not been investigated. We conducted a proof-of-concept study to investigate the efficacy and safety of a six-month CRIC treatment in patients with CSA. METHODS: The EARLY-MYO-CSA trial was a prospective, randomized, controlled trial evaluating the CRIC treatment in patients with CSA with persistent angina pectoris despite receiving ≥ 3-month guideline-recommended optimal medical therapy. The CRIC and control groups received CRIC (at 200 mmHg) or sham CRIC (at 60 mmHg) intervention for 6 months, respectively. The primary endpoint was the 6-month change of myocardial flow reserve (MFR) on single-photon emission computed tomography. The secondary endpoints were changes in rest and stress myocardial blood flow (MBF), angina severity according to the Canadian Cardiovascular Society (CCS) classification, the Seattle Angina Questionnaire (SAQ), and a 6-min walk test (6-MWT). RESULTS: Among 220 randomized CSA patients, 208 (105 in the CRIC group, and 103 in the control group) completed the treatment and endpoint assessments. The mean change in MFR was significantly greater in the CRIC group than in the control group (0.27 ± 0.38 vs. - 0.04 ± 0.25; P < 0.001). MFR increased from 1.33 ± 0.48 at baseline to 1.61 ± 0.53 (P < 0.001) in the CRIC group; however, a similar increase was not seen in the control group (1.35 ± 0.45 at baseline and 1.31 ± 0.44 at follow-up, P = 0.757). CRIC treatment, when compared with controls, demonstrated improvements in angina symptoms assessed by CCS classification (60.0% vs. 14.6%, P < 0.001), all SAQ dimensions scores (P < 0.001), and 6-MWT distances (440 [400-523] vs. 420 [330-475] m, P = 0.016). The incidence of major adverse cardiovascular events was similar between the groups. CONCLUSIONS: CSA patients benefit from 6-month CRIC treatment with improvements in MFR, angina symptoms, and exercise performance. This treatment is well-tolerated and can be recommended for symptom relief in this clinical population. TRIAL REGISTRATION: [chictr.org.cn], identifier [ChiCTR2000038649].

Enzyme-catalyzed synthesis of selenium-doped manganese phosphate for synergistic therapy of drug-resistant colorectal cancer.

BACKGROUND: The development of multidrug resistance (MDR) during postoperative chemotherapy for colorectal cancer substantially reduces therapeutic efficacy. Nanostructured drug delivery systems (NDDSs) with modifiable chemical properties are considered promising candidates as therapies for reversing MDR in colorectal cancer cells. Selenium-doped manganese phosphate (Se-MnP) nanoparticles (NPs) that can reverse drug resistance through sustained release of selenium have the potential to improve the chemotherapy effect of colorectal cancer. RESULTS: Se-MnP NPs had an organic-inorganic hybrid composition and were assembled from smaller-scale nanoclusters. Se-MnP NPs induced excessive ROS production via Se-mediated activation of the STAT3/JNK pathway and a Fenton-like reaction due to the presence of manganese ions (Mn2+). Moreover, in vitro and in vivo studies demonstrated Se-MnP NPs were effective drug carriers of oxaliplatin (OX) and reversed multidrug resistance and induced caspase-mediated apoptosis in colorectal cancer cells. OX@Se-MnP NPs reversed MDR in colorectal cancer by down-regulating the expression of MDR-related ABC (ATP binding cassette) transporters proteins (e.g., ABCB1, ABCC1 and ABCG2). Finally, in vivo studies demonstrated that OX-loaded Se-MnP NPs significantly inhibited proliferation of OX-resistant HCT116 (HCT116/DR) tumor cells in nude mice. CONCLUSIONS: OX@Se-MnP NPs with simple preparation and biomimetic chemical properties represent promising candidates for the treatment of colorectal cancer with MDR.

Enhanced mild-temperature photothermal therapy by pyroptosis-boosted ATP deprivation with biodegradable nanoformulation.

BACKGROUND: Mild-temperature photothermal therapy (mild PTT) is a safe and promising tumor therapeutic modality by alleviating the damage of healthy tissues around the tumor due to high temperature. However, its therapeutic efficiency is easily restricted by heat shock proteins (HSPs). Thus, exploitation of innovative approaches of inhibiting HSPs to enhance mild PTT efficiency is crucial for the clinical application of PTT. RESULTS: Herein, an innovative strategy is reported: pyroptosis-boosted mild PTT based on a Mn-gallate nanoformulation. The nanoformulation was constructed via the coordination of gallic acid (GA) and Mn2+. It shows an acid-activated degradation and releases the Mn2+ and GA for up-regulation of reactive oxygen species (ROS), mitochondrial dysfunction and pyroptosis, which can result in cellular ATP deprivation via both the inhibiton of ATP generation and incresed ATP efflux. The reduction of ATP and accumulation of ROS provide a powerful approach for inhibiting the expression of HSPs, which enables the nanoformulation-mediated mild PTT. CONCLUSIONS: Our in-vitro and in-vivo results demonstrate that this strategy of pyroptosis-assited PTT can achieve efficient mild PTT efficiency for osteosarcoma therapy.

High performance OCTA enabled by combining features of shape, intensity, and complex decorrelation.

Motion contrast optical coherence tomography angiography (OCTA) entails a precise identification of dynamic flow signals from the static background, but an intermediate region with voxels exhibiting a mixed distribution of dynamic and static scatterers is almost inevitable in practice, which degrades the vascular contrast and connectivity. In this work, the static-dynamic intermediate region was pre-defined according to the asymptotic relation between inverse signal-to-noise ratio (iSNR) and decorrelation, which was theoretically derived for signals with different flow rates based on a multi-variate time series (MVTS) model. Then the ambiguous voxels in the intermediate region were further differentiated using a shape mask with adaptive threshold. Finally, an improved OCTA classifier was built by combining shape, iSNR, and decorrelation features, termed as SID-OCTA, and the performance of the proposed SID-OCTA was validated experimentally through mouse retinal imaging.

Long-term performance analysis of chemical filters in clean rooms based on a prediction model.

Chemical filters are the most important devices for removing gas-phase pollutants in clean rooms. However, the testing concentration of chemical filters is too high for reflecting their performance in a real clean room environment. This study tested the adsorption performance of chemical filters in the two most commonly used shapes at different concentrations. Then, the Langmuir equation and Wheeler-Jonas kinetic equation were combined to establish an adsorption performance prediction model of chemical filters under actual conditions. The predicted values of the model were in good agreement with the experimental results, which indicated the high accuracy of the prediction model. The model does not need to test the microscopic parameters of the adsorbent and can maintain high accuracy at low concentrations. A fast method for calculating the service life of chemical filters was also presented. Based on this model, the total cost of using a chemical filter with a high carbon content in microelectronic clean rooms could be decreased by 45% due to decreasing the number of filter replacements over 3 months. So a chemical filter with a high carbon content should be preferred over a filter with low resistance in microelectronic clean rooms.

A Fast and Memory-Efficient Spectral Library Search Algorithm Using Locality-Sensitive Hashing.

With the accumulation of MS/MS spectra collected in spectral libraries, the spectral library searching approach emerges as an important approach for peptide identification in proteomics, complementary to the commonly used protein database searching approach, in particular for the proteomic analyses of well-studied model organisms, such as human. Existing spectral library searching algorithms compare a query MS/MS spectrum with each spectrum in the library with matched precursor mass and charge state, which may become computationally intensive with the rapidly growing library size. Here, the software msSLASH, which implements a fast spectral library searching algorithm based on the Locality-Sensitive Hashing (LSH) technique, is presented. The algorithm first converts the library and query spectra into bit-strings using LSH functions, and then computes the similarity between the spectra with highly similar bit-string. Using the spectral library searching of large real-world MS/MS spectra datasets, it is demonstrated that the algorithm significantly reduced the number of spectral comparisons, and as a result, achieved 2-9X speedup in comparison with existing spectral library searching algorithm SpectraST. The spectral searching algorithm is implemented in C/C++, and is ready to be used in proteomic data analyses.

Full-Spectrum Prediction of Peptides Tandem Mass Spectra using Deep Neural Network.

The ability to predict tandem mass (MS/MS) spectra from peptide sequences can significantly enhance our understanding of the peptide fragmentation process and could improve peptide identification in proteomics. However, current approaches for predicting high-energy collisional dissociation (HCD) spectra are limited to predict the intensities of expected ion types, that is, the a/b/c/x/y/z ions and their neutral loss derivatives (referred to as backbone ions). In practice, backbone ions only account for <70% of total ion intensities in HCD spectra, indicating many intense ions are ignored by current predictors. In this paper, we present a deep learning approach that can predict the complete spectra (both backbone and nonbackbone ions) directly from peptide sequences. We made no assumptions or expectations on which kind of ions to predict but instead predicting the intensities for all possible m/z. Training this model needs no annotations of fragment ion nor any prior knowledge of the fragmentation rules. Our analyses show that the predicted 2+ and 3+ HCD spectra are highly similar to the experimental spectra, with average full-spectrum cosine similarities of 0.820 (±0.088) and 0.786 (±0.085), respectively, very close to the similarities between the experimental replicated spectra. In contrast, the best-performed backbone only models can only achieve an average similarity below 0.75 and 0.70 for 2+ and 3+ spectra, respectively. Furthermore, we developed a multitask learning (MTL) approach for predicting spectra of insufficient training samples, which allows our model to make accurate predictions for electron transfer dissociation (ETD) spectra and HCD spectra of less abundant charges (1+ and 4+).

Investigating the biomechanical function of the plate-type external fixator in the treatment of tibial fractures: a biomechanical study.

BACKGROUND: The design of an external fixator with the optimal biomechanical function and the lowest profile has been highly pursued, as fracture healing is dependent on the stability and durability of fixation, and a low profile is more desired by patients. The plate-type external fixator, a novel prototype of an external tibial fixation device, is a low profile construct. However, its biomechanical properties remain unclear. The objective of this study was to investigate the stiffness and strength of the plate-type external fixator and the unilateral external fixator. We hypothesized that the plate-type external fixator could provide higher stiffness while retaining sufficient strength. METHODS: Fifty-four cadaver tibias underwent a standardized midshaft osteotomy to create a fracture gap model to simulate a comminuted diaphyseal fracture. All specimens were randomly divided into three groups of eighteen specimens each and stabilized with either a unilateral external fixator or two configurations of the plate-type external fixator. Six specimens of each configuration were tested to determine fixation stiffness in axial compression, four-point bending, and torsion, respectively. Afterwards, dynamic loading until failure was performed in each loading mode to determine the construct strength and failure mode. RESULTS: The plate-type external fixator provided higher stiffness and strength than the traditional unilateral external fixator. The highest biomechanics were observed for the classical plate-type external fixator, closely followed by the extended plate-type external fixator. CONCLUSIONS: The plate-type external fixator is stiffer and stronger than the traditional unilateral external fixator under axial compression, four-point bending and torsion loading conditions.

Association Between Transforming Growth Factor-ß1 T869C Gene Polymorphism and Diabetic Nephropathy: A Meta-Analysis in the Chinese Population.

BACKGROUND: An updated meta-analysis was performed to clarify the effects of TGF-ß1 T869C polymorphism on the risk of diabetic nephropathy (DN) in the Chinese population. METHODS: The studies were searched using PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Ser-vice Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) up to October 2018. RESULTS: A total of 8 studies including 1,075 DN cases, 610 healthy controls, and 901 diabetes mellitus (DM) con-trols were involved in this meta-analysis. Overall, a significantly decreased risk of DN was associated with all vari-ants of TGF-ß1 T869C when compared with the healthy group (T vs. C, OR = 0.71, 95% CI = 0.61 - 0.83; TT vs. CC, OR = 0.51, 95% CI = 0.37 - 0.69; TT + CT vs. CC, OR = 0.64, 95% CI = 0.51 - 0.82; TT vs. CC + CT, OR = 0.62, 95% CI = 0.48 - 0.82) or DM (T vs. C, OR = 0.65, 95% CI = 0.56 - 0.76; TT vs. CC, OR = 0.31, 95% CI = 0.17 - 0.55; TT + CT vs. CC, OR = 0.67, 95% CI = 0.54 - 0.84; TT vs. CC + CT, OR = 0.27, 95% CI = 0.13 - 0.55), as well as their combinations (T vs. C, OR = 0.67, 95% CI = 0.60 - 0.76; TT vs. CC, OR = 0.34, 95% CI = 0.21 - 0.56; TT + CT vs. CC, OR = 0.67, 95% CI = 0.56 - 0.80; TT vs. CC + CT, OR = 0.32, 95% CI = 0.17 - 0.57). The sub-group analyses stratified by geographic areas revealed significant results in South China. CONCLUSIONS: This meta-analysis showed that the TGF-ß1 T869C variants may influence DN risk in Chinese, and further studies with gene-gene and gene-environment interactions are required to confirm this conclusion.

Reduction Osteotomy versus Extensive Release on Clinical Outcome Measures in Simultaneous Bilateral Total Knee Arthroplasty.

BACKGROUND During total knee arthroplasty (TKA) in varus knee deformities, reduction osteotomy (RO) and medial soft tissue release are alternative techniques to aid in achieving deformity correction. In this study, we investigated the effect of RO compared to extensive medial soft tissue release (ER) on clinical outcome measures in simultaneous bilateral TKA. MATERIAL AND METHODS We prospectively enrolled 24 patients (48 knees) with bilateral varus knee deformity from July 2014 to December 20l5. For each patient, one knee was assigned to the RO group and the contralateral knee was assigned to ER group. One year postoperative, follow-up outcomes were collected and analyzed. RESULTS Time to 90° flexion of the knee was significantly different in the RO group (1.6±0.3 days) compared to the ER group (2.0±0.4 days) (p<0.001). Using a 10-item patient reported outcome questionnaire, total scores were significantly different between the RO group (86.3±3.2) and the ER group (82.4±2.7) (p<0.001). Analysis of variance showed a significant difference on the visual analogue scale (VAS) score (p<0.001) but no significant difference in the range of motion (ROM) of the knee (p>0.05) during the follow-up year. CONCLUSIONS Knees treated with RO were associated with greater improvements in pain and function than knees treated with conventional ER technique. Additionally, RO technique did not confer an increased risk for adverse clinical outcomes. RO may therefore by a safe method to decrease postoperative pain, achieve earlier functional recovery, and increase patients' subjective satisfaction after TKA.

Precise soil coverage in potato planting through plastic film using real-time image recognition with YOLOv4-tiny.

Planting potatoes through plastic film with incomplete or excessive soil coverage over seed holes significantly impairs yield. Existing covering methods rely solely on mechanical transmissions, leading to bulky and inconsistent soil coverage of the seed holes. This paper reports an innovative method using a precise soil covering device based on the YOLOv4-tiny real-time object detection system to accurately identify potato plastic film holes and cover them with soil. The system adopts a lightweight and high-precision detection scheme, balancing increased network depth with reduced computation. It can identify holes in the plastic film in real-time and with high accuracy. To verify the effectiveness of YOLOv4-tiny real-time object detection system, a precise soil covering device based on this detection system has been designed and applied to a double crank multi-rod hill-drop planter. Field tests revealed that the system's average accuracy rate for detecting holes is approximately 98%, with an average processing time of 15.15 ms per frame. This fast and accurate performance, combined with the device's robust real-time operation and anti-interference capabilities during soil covering, effectively reduce the problems of soil cover omission and repeated covering caused by existing mechanical transmission methods. The findings reported in this paper are valuable for the development of autonomous potato plastic film precise soil covering devices for commercial use.

Multidimensional Refinement Graph Convolutional Network With Robust Decouple Loss for Fine-Grained Skeleton-Based Action Recognition.

Graph convolutional networks (GCNs) have been widely used in skeleton-based action recognition. However, existing approaches are limited in fine-grained action recognition due to the similarity of interclass data. Moreover, the noisy data from pose extraction increase the challenge of fine-grained recognition. In this work, we propose a flexible attention block called channel-variable spatial-temporal attention (CVSTA) to enhance the discriminative power of spatial-temporal joints and obtain a more compact intraclass feature distribution. Based on CVSTA, we construct a multidimensional refinement GCN (MDR-GCN) that can improve the discrimination among channel-, joint-, and frame-level features for fine-grained actions. Furthermore, we propose a robust decouple loss (RDL) that significantly boosts the effect of the CVSTA and reduces the impact of noise. The proposed method combining MDR-GCN with RDL outperforms the known state-of-the-art skeleton-based approaches on fine-grained datasets, FineGym99 and FSD-10, and also on the coarse NTU-RGB + D 120 dataset and NTU-RGB + D X-view version. Our code is publicly available at https://github.com/dingyn-Reno/MDR-GCN.

Engineering Bimetallic Polyphenol for Mild Photothermal Osteosarcoma Therapy and Immune Microenvironment Remodeling by Activating Pyroptosis and cGAS-STING Pathway.

The immunosuppressive tumor microenvironment (ITME) of osteosarcoma (OS) poses a significant obstacle to the efficacy of existing immunotherapies. Despite the attempt of novel immune strategies such as immune checkpoint inhibitors and tumor vaccines, their effectiveness remains suboptimal due to the inherent difficulty in mitigating ITME simultaneously from both the tumor and immune system. The promotion of anti-tumor immunity through the induction of immunogenic cell death and activation of the cGAS-STING pathway has emerged as potential strategies to counter the ITME and stimulate systemic antitumor immune responses. Here, a bimetallic polyphenol-based nanoplatform (Mn/Fe-Gallate nanoparticles coated with tumor cell membranes is presented, MFG@TCM) which combines with mild photothermal therapy (PTT) for reversing ITME via simultaneously inducing pyroptosis in OS cells and activating the cGAS-STING pathway in dendritic cells (DCs). The immunostimulatory pathways, through the syngeneic effect, exerted a substantial positive impact on promoting the secretion of damage-associated molecular patterns (DAMPs) and proinflammatory cytokines, which favors remodeling the immune microenvironment. Consequently, effector T cells led to a notable antitumor immune response, effectively inhibiting the growth of both primary and distant tumors. This study proposes a new method for treating OS using mild PTT and immune mudulation, showing promise in overcoming current treatment limitations.