Decreased Expression of PLD2 Promotes EMT in Colorectal Cancer Invasion and Metastasis.

Background and Objectives: PLD2 has been identified as playing a critical role in cancer cell motility and migration and other pathophysiological processes. We investigated the expression of PLD2 and its biological functions and clinical implications in human colorectal cancer. Materials and Methods: In this study, the expressions of PLD2 were analyzed in CRC cell lines and CRC samples by RT-PCR, western blot and immunohistochemistry. The PLD enzyme activity was studied using an PLD detection kit. We also performed matrigel invasion assay to evaluate the invasive capabilities in CRC cells. The expressions of EMT-related markers were quantified at mRNA and protein level using RT-PCR and western blot. We performed high-throughput RNA sequencing on PLD2 knockdown and overexpression CRC cell lines to explore the changes in gene expression associated with PLD2. Result: Herein, we showed that PLD2 expression was relatively low in CRC cell lines and CRC samples and PLD2 deficiency was significantly correlated with more advanced clinical phenotype regarding lymphatic and distant metastasis and poor patient survival. We also detected that PLD2 knockdown favored epithelial-mesenchymal transition (EMT) and thus promoted CRC invasion and metastasis. Further exploration uncovered that the expressions of several important genes closely related to metabolic pathways in CRC were noticeably altered due to PLD2 deficiency, including ID1, IFIT4, OASL, IFIT2 and CTAG2. Conclusion: Our results revealed that PLD2 deficiency promotes cell invasion and metastasis in CRC via EMT indicating PLD2 might have an important implication in carcinogenesis and progression and would be a new therapeutic target for cancer treatment.

Selective bioaccumulation of polystyrene nanoplastics in fetal rat brain and damage to myelin development.

Micro(nano)plastic, as a new type of environmental pollutant, have become a potential threat to the life and health of various stages of biology. However, it is not yet clear whether they will affect brain development in the fetal stage. Therefore, this study aims to explore the potential effects of nanoplastics on the development of fetal rat brains. To assess the allocation of NPs (25 nm and 50 nm) in various regions of the fetal brain, pregnant rats were exposed to concentrations (50, 10, 2.5, and 0.5 mg/kg) of PS-NPs. Our results provided evidence of the transplacental transfer of PS-NPs to the fetal brain, with a prominent presence observed in several cerebral regions, notably the cerebellum, hippocampus, striatum, and prefrontal cortex. This distribution bias might be linked to the developmental sequence of each brain region. Additionally, we explored the influence of prenatal exposure on the myelin development of the cerebellum, given its the highest PS-NP accumulation in offspring. Compared with control rats, PS-NPs exposure caused a significant reduction in myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) expression, a decrease in myelin thickness, an increase in cell apoptosis, and a decline in the oligodendrocyte population. These effects gave rise to motor deficits. In conclusion, our results identified the specific distribution of NPs in the fetal brain following prenatal exposure and revealed that prenatal exposure to PS-NPs can suppress myelin formation in the cerebellum of the fetus.

Global drivers of the conservation-invasion paradox.

The conservation-invasion paradox (CIP) refers to a long-term phenomenon wherein species threatened in their native range can sustain viable populations when introduced to other regions. Understanding the drivers of CIP is helpful for conserving threatened species and managing invasive species, which is unfortunately still lacking. We compiled a global data set of 1071 introduction events, including 960 CIP events (successful establishment of threatened species outside its native range) and 111 non-CIP events (unsuccessful establishment of threatened species outside its native range after introduction), involving 174 terrestrial vertebrates. We then tested the relative importance of various predictors at the location, event, and species levels with generalized linear mixed models and model averaging. Successful CIP events occurred across taxonomic groups and biogeographic realms, especially for the mammal group in the Palearctic and Australia. Locations of successful CIP events had fewer native threat factors, especially less climate warming in invaded regions. The probability of a successful CIP event was highest when species introduction efforts were great and there were more local congeners and fewer natural enemies. These results can inform threatened species ex situ conservation and non-native invasive species mitigation.

Causantes mundiales de la paradoja conservación­invasión Resumen La paradoja de conservación­invasión (PCI) se refiere al evento a largo plazo en el que las especies amenazadas en su distribución nativa puedan mantener poblaciones viables cuando se les introduce a otras regiones. Es de mucha ayuda para la conservación de especies amenazadas y el manejo de especies invasoras entender las causantes de la PCI, entendimiento que todavía es escaso. Compilamos un conjunto mundial de datos de 174 vertebrados terrestres en 1071 eventos de introducción, incluyendo 960 eventos de PCI (el establecimiento exitoso de especies amenazadas fuera de su distribución nativa) y 111 eventos no PCI (el fracaso en el establecimiento de especies amenazadas fuera de su distribución nativa después de la introducción). Después analizamos con modelos lineales mixtos generalizados y promedio de modelos la importancia relativa de varios pronosticadores en la localidad, en el evento y a nivel de especie. Los eventos exitosos de PCI ocurrieron en todos los grupos taxonómicos y en todos los reinos biogeográficos, especialmente para los mamíferos del Paleártico y Australia. Las localidades de los eventos exitosos de PCI tuvieron menos factores nativos de amenaza, especialmente un menor calentamiento climático en las regiones invadidas. La probabilidad de que un evento de PCI sea exitoso fue mayor cuando los esfuerzos de introducción fueron mayores y hubo más congéneres locales y menos enemigos naturales. Estos resultados pueden orientar la conservación ex situ de especies y la mitigación de especies invasoras no nativas.

Effects of walking speeds on lower extremity kinematic synergy in toe vertical position control: An experimental study.

BACKGROUND: This study aimed to investigate whether lower limb joints mutually compensate for each other, resulting in motor synergy that suppresses toe vertical position fluctuation, and whether walking speeds affect lower limb synergy. METHODS: Seventeen male university students walked at slow (0.85 ±â€…0.04 m/s), medium (1.43 ±â€…0.05 m/s) and fast (1.99 ±â€…0.06 m/s) speeds on a 15-m walkway while lower limb kinematic data were collected. Uncontrolled manifold analysis was used to quantify the strength of synergy. Two-way (speed × phase) repeated-measures analysis of variance was used to analyze all dependent variables. RESULTS: A significant speed-by-phase interaction was observed in the synergy index (SI) (P  < .001). At slow walking speeds, subjects had greater SI during mid-swing (P  < .001), while at fast walking speeds, they had greater SI during early-swing (P  < .001). During the entire swing phase, fast walking exhibited lower SI values than medium (P  = .005) and slow walking (P  = .027). CONCLUSION: Kinematic synergy plays a crucial role in controlling toe vertical position during the swing phase, and fast walking exhibits less synergy than medium and slow walking. These findings contribute to a better understanding of the role of kinematic synergy in gait stability and have implications for the development of interventions aimed at improving gait stability and reducing the risk of falls.

Precise Modulation of Pericyte Dysfunction by a Multifunctional Nanoprodrug to Ameliorate Alzheimer's Disease.

Pericyte dysfunction severely undermines cerebrovascular integrity and exacerbates neurodegeneration in Alzheimer's disease (AD). However, pericyte-targeted therapy is a yet-untapped frontier for AD. Inspired by the elevation of vascular cell adhesion molecule-1 (VCAM-1) and reactive oxygen species (ROS) levels in pericyte lesions, we fabricated a multifunctional nanoprodrug by conjugating the hybrid peptide VLC, a fusion of the VCAM-1 high-affinity peptide VHS and the neuroprotective apolipoprotein mimetic peptide COG1410, to curcumin (Cur) through phenylboronic ester bond (VLC@Cur-NPs) to alleviate complex pericyte-related pathological changes. Importantly, VLC@Cur-NPs effectively homed to pericyte lesions via VLC and released their contents upon ROS stimulation to maximize their regulatory effects. Consequently, VLC@Cur-NPs markedly increased pericyte regeneration to form a positive feedback loop and thus improved neurovascular function and ultimately alleviated memory defects in APP/PS1 transgenic mice. We present a promising therapeutic strategy for AD that can precisely modulate pericytes and has the potential to treat other cerebrovascular diseases.

Metal bond strength regulation enables large-scale synthesis of intermetallic nanocrystals for practical fuel cells.

Structurally ordered L10-PtM (M = Fe, Co, Ni and so on) intermetallic nanocrystals, benefiting from the chemically ordered structure and higher stability, are one of the best electrocatalysts used for fuel cells. However, their practical development is greatly plagued by the challenge that the high-temperature (>600 °C) annealing treatment necessary for realizing the ordered structure usually leads to severe particle sintering, morphology change and low ordering degree, which makes it very difficult for the gram-scale preparation of desirable PtM intermetallic nanocrystals with high Pt content for practical fuel cell applications. Here we report a new concept involving the low-melting-point-metal (M' = Sn, Ga, In)-induced bond strength weakening strategy to reduce Ea and promote the ordering process of PtM (M = Ni, Co, Fe, Cu and Zn) alloy catalysts for a higher ordering degree. We demonstrate that the introduction of M' can reduce the ordering temperature to extremely low temperatures (≤450 °C) and thus enable the preparation of high-Pt-content (≥40 wt%) L10-Pt-M-M' intermetallic nanocrystals as well as ten-gram-scale production. X-ray spectroscopy studies, in situ electron microscopy and theoretical calculations reveal the fundamental mechanism of the Sn-facilitated ordering process at low temperatures, which involves weakened bond strength and consequently reduced Ea via Sn doping, the formation and fast diffusion of low-coordinated surface free atoms, and subsequent L10 nucleation. The developed L10-Ga-PtNi/C catalysts display outstanding performance in H2-air fuel cells under both light- and heavy-duty vehicle conditions. Under the latter condition, the 40% L10-Pt50Ni35Ga15/C catalyst delivers a high current density of 1.67 A cm-2 at 0.7 V and retains 80% of the current density after extended 90,000 cycles, which exceeds the United States Department of Energy performance metrics and represents among the best cathodic electrocatalysts for practical proton-exchange membrane fuel cells.

From virus to immune system: Harnessing membrane-derived vesicles to fight COVID-19 by interacting with biological molecules.

Emerging and re-emerging viral pandemics have emerged as a major public health concern. Highly pathogenic coronaviruses, which cause severe respiratory disease, threaten human health and socioeconomic development. Great efforts are being devoted to the development of safe and efficacious therapeutic agents and preventive vaccines to combat them. Nevertheless, the highly mutated virus poses a challenge to drug development and vaccine efficacy, and the use of common immunomodulatory agents lacks specificity. Benefiting from the burgeoning intersection of biological engineering and biotechnology, membrane-derived vesicles have shown superior potential as therapeutics due to their biocompatibility, design flexibility, remarkable bionics, and inherent interaction with phagocytes. The interactions between membrane-derived vesicles, viruses, and the immune system have emerged as a new and promising topic. This review provides insight into considerations for developing innovative antiviral strategies and vaccines against SARS-CoV-2. First, membrane-derived vesicles may provide potential biomimetic decoys with a high affinity for viruses to block virus-receptor interactions for early interruption of infection. Second, membrane-derived vesicles could help achieve a balanced interplay between the virus and the host's innate immunity. Finally, membrane-derived vesicles have revealed numerous possibilities for their employment as vaccines.

Advances on the Mechanisms and Therapeutic Strategies in Non-coding CGG Repeat Expansion Diseases.

Non-coding CGG repeat expansions within the 5' untranslated region are implicated in a range of neurological disorders, including fragile X-associated tremor/ataxia syndrome, oculopharyngeal myopathy with leukodystrophy, and oculopharyngodistal myopathy. This review outlined the general characteristics of diseases associated with non-coding CGG repeat expansions, detailing their clinical manifestations and neuroimaging patterns, which often overlap and indicate shared pathophysiological traits. We summarized the underlying molecular mechanisms of these disorders, providing new insights into the roles that DNA, RNA, and toxic proteins play. Understanding these mechanisms is crucial for the development of targeted therapeutic strategies. These strategies include a range of approaches, such as antisense oligonucleotides, RNA interference, genomic DNA editing, small molecule interventions, and other treatments aimed at correcting the dysregulated processes inherent in these disorders. A deeper understanding of the shared mechanisms among non-coding CGG repeat expansion disorders may hold the potential to catalyze the development of innovative therapies, ultimately offering relief to individuals grappling with these debilitating neurological conditions.

Novel insights into dimethylsulfoniopropionate cleavage by deep subseafloor fungi.

Dimethylsulfoniopropionate (DMSP), a key organic sulfur compound in marine and subseafloor sediments, is degraded by phytoplankton and bacteria, resulting in the release of the climate-active volatile gas dimethylsulfide (DMS). However, it remains unclear if dominant eukaryotic fungi in subseafloor sediments possess specific abilities and metabolic mechanisms for DMSP degradation and DMS formation. Our study provides the first evidence that fungi from coal-bearing sediments ∼2 km below the seafloor, such as Aspergillus spp., Chaetomium globosum, Cladosporium sphaerospermum, and Penicillium funiculosum, can degrade DMSP and produce DMS. In Aspergillus sydowii 29R-4-F02, which exhibited the highest DMSP-dependent DMS production rate (16.95 pmol/µg protein/min), two DMSP lyase genes, dddP and dddW, were identified. Remarkably, the dddW gene, previously observed only in bacteria, was found to be crucial for fungal DMSP cleavage. These findings not only extend the list of fungi capable of degrading DMSP, but also enhance our understanding of DMSP lyase diversity and the role of fungi in DMSP decomposition in subseafloor sedimentary ecosystems.

Portable Mass Spectrometry for On-site Detection of Hazardous Volatile Organic Compounds via Robotic Extractive Sampling.

Various hazardous volatile organic compounds (VOCs) are frequently released into environments during accidental events that cause many hazards to ecosystems and humans. Therefore, rapid, sensitive, and on-site detection of hazardous VOCs is crucial to understand their compositions, characteristics, and distributions in complex environments. However, manual handling of hazardous VOCs remains a challenging task, because of the inaccessible environments and health risk. In this work, we designed a quadruped robotic sampler to reach different complex environments for capturing trace hazardous VOCs using a needle trap device (NTD) by remote manipulation. The captured samples were rapidly identified by portable mass spectrometry (MS) within minutes. Rapid detection of various hazardous VOCs including toxicants, chemical warfare agents, and burning materials from different environments was successfully achieved using this robot-MS system. On-site detection of 83 typical hazardous VOCs was examined. Acceptable analytical performances including low detection limits (at subng/mL level), good reproducibility (relative standard deviation (RSD) < 20%, n = 6), excellent quantitative ability (R2 > 0.99), and detection speed (within minutes) were also obtained. Our results show that the robot-MS system has excellent performance including safety, controllability, applicability, and robustness under dangerous chemical conditions.

Photodynamic therapy for the treatment of port-wine stains in phakomatosis pigmentovascularis.

BACKGROUND: Phakomatosis pigmentovascularis (PPV) is a rare congenital syndrome. Only a few studies have reported the treatment of PPV, including a case using photodynamic therapy (PDT) to treat PPV-associated port-wine stains (PWS). OBJECTIVE: To investigating the efficacy and adverse effects of hemoporfin-PDT in PPV-associated PWS. METHODS: The efficacy and adverse effects in patients with PPV who underwent two sessions of hemoporfin-PDT from January 2019 to December 2022 were retrospectively analyzed. RESULTS: Twenty patients were included (13 females, 7 males, age range: 2-31 years; mean: 8.20 ± 8.92 years). Two, nine, seven, and two patients had PPV types Ia, IIa, IIb, and IIIa, respectively. After two treatments, the visual evaluation indicated the color of the PWS in 4, 5, 6, and 5 patients showed poor, fair, good, and excellent improvements, respectively. The combined good and excellent improvement rates in patients with PWS and pigmentary nevus overlapping in the same treatment area and in patients with PWS in the treatment areas only were 33.3% versus 87.5%, respectively, and were significantly different (p = 0.02). Minor side effects, such as edema, scabbing, hyperpigmentation, and blistering, were observed in some patients after PDT. CONCLUSION: Hemoporfin-PDT is an effective treatment for PPV-associated PWS. Patients with PWS and pigmentary nevus overlapping in the same treatment area showed poorer efficacy than patients with PWS in the treatment areas only.

Polyvinylidene fluoride/graphene oxide/polyimide composite high-efficiency PM2.5 filtration nanofiber membranes.

Particulate air pollution is a global environmental problem, with PM2.5 being the primary pollutant. One of the most effective ways to remove particles from the air is through filtration. Therefore, high-performance air filters are urgently needed to combat the harm caused by PM2.5. This study uses an electrospinning technique to prepare high-efficiency polyvinylidene fluoride/graphene oxide/polyimide nanofiber membranes. These composite nanofiber membranes demonstrate high filtration efficiency (99.6%), low pressure drop (123 Pa), remarkable thermal stability (450 °C), and excellent mechanical strength (7 MPa). Considering the advantages, these highly efficient nanofiber membranes can find advanced applications in industrial and civil infrastructures.

Study on coal pulverization characteristics and gas desorption mechanism based on impact crushing experiment.

The coal's particle size distribution properties after pulverization and the gas desorption behavior driven by pulverization are of profound meaning to the study of coal and gas outburst mechanism. In this paper, based on the impact crushing experiment, the tectonic coal and primary coal are crushed under different impact energy conditions. After screening the broken coal, the particle size distribution law is analyzed, and the characterization function suitable for the particle size distribution of coal particles after crushing is determined. The relationship between crushing work and new surface area and fractal dimension of coal body is discussed. The consequences indicated that the mass proportion of tectonic coal below 0.074 mm particle size is much huger than that of raw coal. G-S, R-R, and fractal distribution model describe the best particle size distribution of the two coals in the scope of 0.074∼4 mm. The new surface area added increases with the crushing work, and the tectonic coal is 1.34-1.96 times that of the raw coal. The fractal dimension diminishes first and then increases with the crushing work ratio. In addition, the gas desorption amount of coal particles with different particle sizes after coal pulverization was measured, and a dynamic model suitable for coal pulverization-driven gas desorption was established, and the experimental results were verified. The research results of this paper can provide experimental and theoretical basis for the analysis of energy dissipation in coal and gas outburst.

Gut microbiota and serum metabolite signatures along the colorectal adenoma-carcinoma sequence: Implications for early detection and intervention.

AIM: Our study focuses on the microbial and metabolomic profile changes during the adenoma stage, as adenomas can be considered potential precursors to colorectal cancer through the adenoma-carcinoma sequence. Identifying possible intervention targets at this stage may aid in preventing the progression of colorectal adenoma (CRA) to malignant lesions. Furthermore, we evaluate the efficacy of combined microbial and metabolite biomarkers in detecting CRA. METHODS: Fecal metagenomic and serum metabolomic analyses were performed for the discovery of alterations of gut microbiome and metabolites in CRA patients (n = 26), Colorectal cancer (CRC) patients (n = 19), Familial Adenomatous Polyposis (FAP) patients (n = 10), and healthy controls (n = 20). Finally, analyzing the associations between gut microbes and metabolites was performed by a Receiver Operating Characteristic (ROC) curve. RESULTS: Our analysis present that CRA patients differ significantly in gut microflora and serum metabolites compared with healthy controls, especially for Lachnospiraceae and Parasutterella. Its main metabolite, butyric acid, concentrations were raised in CRA patients compared with the healthy controls, indicating its role as a promoter of colorectal tumorigenesis. α-Linolenic acid and lysophosphatidylcholine represented the other healthy metabolite for CRA. Combining five microbial and five metabolite biomarkers, we differentiated CRA from CRC with an Area Under the Curve (AUC) of 0.85 out of this performance vastly superior to the specificity recorded by traditional markers CEA and CA199 in such differentiation of these conditions. CONCLUSIONS: The study underlines significant microbial and metabolic alterations in CRA with a novel insight into screening and early intervention of its tumorigenesis.

Highly Curved Defect Sites: How Curvature Effect Influences Metal-Free Defective Carbon Electrocatalysts.

Topological defects are widely recognized as effective active sites toward a variety of electrochemical reactions. However, the role of defect curvature is still not fully understood. Herein, carbon nanomaterials with rich topological defect sites of tunable curvature is reported. The curved defective surface is realized by controlling the high-temperature pyrolytic shrinkage process of precursors. Theoretical calculations demonstrate bending the defect sites can change the local electronic structure, promote the charge transfer to key intermediates, and lower the energy barrier for oxygen reduction reaction (ORR). Experimental results convince structural superiority of highly-curved defective sites, with a high kinetic current density of 22.5 mA cm-2 at 0.8 V versus RHE for high-curvature defective carbon (HCDC), ≈18 times that of low-curvature defective carbon (LCDC). Further raising the defect densities in HCDC leads to the dual-regulated products (HCHDC), which exhibit exceptionally outstanding ORR activity in both alkaline and acidic media (half-wave potentials: 0.88 and 0.74 V), outperforming most of the reported metal-free carbon catalysts. This work uncovers the curvature-activity relationship in carbon defect for ORR and provides new guidance to design advanced catalysts via curvature-engineering.

Fast high quality computational ghost imaging based on saliency variable sampling detection.

Fast computational ghost imaging with high quality and ultra-high-definition resolution reconstructed images has important application potential in target tracking, biological imaging and other fields. However, as far as we know, the resolution (pixels) of the reconstructed image is related to the number of measurements. And the limited resolution of reconstructed images at low measurement times hinders the application of computational ghost imaging. Therefore, in this work, a new computational ghost imaging method based on saliency variable sampling detection is proposed to achieve high-quality imaging at low measurement times. This method physically variable samples the salient features and realizes compressed detection of computational ghost imaging based on the salient periodic features of the bucket detection signal. Numerical simulation and experimental results show that the reconstructed image quality of our method is similar to the compressed sensing method at low measurement times. Even at 500 (sampling rate 0.76 % ) measurement times, the reconstructed image of the method still has the target features. Moreover, the 2160 × 4096 (4K) pixels ultra-high-definition resolution reconstructed images can be obtained at only a sampling rate of 0.11 % . This method has great potential value in real-time detection and tracking, biological imaging and other fields.

Hidden blood loss and its influencing factors after cement augmentation for vertebral metastasis.

Introduction: Few studies have focused on the risk factors for hidden blood loss (HBL) during cement augmentation surgery for pathologic vertebral compression fraction (PVCFs). Method: From January 2014 to December 2020, the clinical data of 169 PVCF patients (283 levels) who underwent cement augmentation were retrospectively analysed. HBL was calculated according to the linear Gross formula using the patient's average Hct during the perioperative course and PBV. Multivariate linear regression analysis was performed to evaluate the independent factors associated with HBL. Results: The mean HBL was 448.2 ± 267.2 ml, corresponding to 10.8% ± 6.2% of the patient blood volume (PBV). There were significant differences between pre- and postoperative haematocrit (Hct) (P < 0.001) and Hb (P < 0.001), and 132 patients developed anaemia postoperatively, while 79 patients had anaemia preoperatively (P < 0.001). Multivariate linear regression revealed that bone lesion quality (p = 0.028), number of PVCFs (p = 0.002), amount of bone cement (p = 0.027), bone cement leakage (p = 0.001), and percentage of vertebral height loss (VHL) (p = 0.011) were independent risk factors for HBL. Conclusion: In conclusion, patients with lytic vertebral destruction, larger amounts of bone cement, greater amounts of bone cement leakage, more PVCF(s), and greater percentages of VHL may be more prone to HBL.

Comparison of neoadjuvant chemotherapy response and prognosis between HR-low/HER2-negative BC and TNBC: an exploratory real-world multicentre cohort study.

Objective: Hormone receptor (HR)-low/HER2-negative breast cancers (BCs) are more likely to be basal-like BCs, with similar molecular features and gene expression profiles to HR-negative (estrogen receptor <1% or negative and progesterone receptor <1% or negative) BCs. Recently, with the clinical application of adjuvant intensive therapy for triple-negative breast cancer (TNBC), the prognosis of TNBC patients without pathological complete response (pCR) has significantly improved. Therefore, it is necessary to reanalyse the prognostic characteristics of clinically high-risk HR-low/HER2-negative BC. Methods: According to the inclusion and exclusion standards, 288 patients with HR-low/HER2-negative BC and TNBC who received NAC and were followed up between 2015 and 2022 at three breast centres in Hunan Province, China, were enrolled. Inverse probability of treatment weighting (IPTW) was utilized to mitigate imbalances in baseline characteristics between the HR-low/HER2-negative BC group and TNBC group regarding event-free survival (EFS) and overall survival (OS). The primary clinical endpoints were pCR and EFS, while the secondary endpoints included OS, objective response rate (ORR), and clinical benefit rate (CBR). Results: The pCR rate (27.1% vs. 28.0%, P = 1.000), ORR rate (76.9% vs. 78.3%, P = 0.827) and CBR rate (89.7% vs. 96.5%, P = 0.113) after NAC were similar between the HR-low/HER2-negative BC and the TNBC group. EFS in patients with non-pCR from the 2 groups was significantly inferior in comparison to patients with pCR (P = 0.001), and the 3-year EFS was 94.74% (95% CI = 85.21% to 100.00%) and 57.39% (95% CI =43.81% to 75.19%) in patients with pCR and non-pCR from the HR-low/HER2-negative BC group, respectively, and 89.70% (95% CI = 82.20% to 97.90%) and 69.73% (95% CI = 62.51% to 77.77%) in the TNBC patients with pCR and non-pCR, respectively. Conclusions: In the real world, the therapeutic effects of NAC for HR-low/HER2-negative BCs and TNBCs were similar. EFS of patients with non-pCR in the HR-low/HER2-negative BC group was inferior to that of the TNBC group with non-pCR, suggesting that it is necessary to explore new adjuvant intensive therapy strategies for these patients.

Subgraph-Aware Graph Kernel Neural Network for Link Prediction in Biological Networks.

Identifying links within biological networks is important in various biomedical applications. Recent studies have revealed that each node in a network may play a unique role in different links, but most link prediction methods overlook distinctive node roles, hindering the acquisition of effective link representations. Subgraph-based methods have been introduced as solutions but often ignore shared information among subgraphs. To address these limitations, we propose a Subgraph-aware Graph Kernel Neural Network (SubKNet) for link prediction in biological networks. Specifically, SubKNet extracts a subgraph for each node pair and feeds it into a graph kernel neural network, which decomposes each subgraph into a combination of trainable graph filters with diversity regularization for subgraph-aware representation learning. Additionally, node embeddings of the network are extracted as auxiliary information, aiding in distinguishing node pairs that share the same subgraph. Extensive experiments on five biological networks demonstrate that SubKNet outperforms baselines, including methods especially designed for biological networks and methods adapted to various networks. Further investigations confirm that employing graph filters to subgraphs helps to distinguish node roles in different subgraphs, and the inclusion of diversity regularization further enhances its capacity from diverse perspectives, generating effective link representations that contribute to more accurate link prediction.

Bone morphogenetic protein-6 suppresses TGF-ß2-induced epithelial-mesenchymal transition in retinal pigment epithelium.

AIM: To evaluate the effect of bone morphogenetic protein-6 (BMP-6) on transforming growth factor (TGF)-ß2-induced epithelial-mesenchymal transition (EMT) in retinal pigment epithelium (RPE). METHODS: Adult retinal pigment epithelial cell line (ARPE-19) were randomly divided into control, TGF-ß2 (5 µg/L), and BMP-6 small interfering RNA (siRNA) group. The cell morphology was observed by microscopy, and the cell migration ability were detected by Transwell chamber. The EMT-related indexes and BMP-6 protein levels were detected by Western blotting. Furthermore, a BMP-6 overexpression plasmid was constructed and RPE cells were divided into the control group, TGF-ß2+empty plasmid group, BMP-6 overexpression group, and TGF-ß2+BMP-6 overexpression group. The EMT-related indexes and extracellular regulated protein kinases (ERK) protein levels were detected. RESULTS: Compared with the control group, the migration of RPE cells in the TGF-ß2 group was significantly enhanced. TGF-ß2 increased the protein expression levels of α-smooth muscle actin (α-SMA), fibronectin and vimentin but significantly decreased the protein levels of E-cadherin and BMP-6 (P<0.05) in RPE. Similarly, the migration of RPE cells in the BMP-6 siRNA group was also significantly enhanced. BMP-6 siRNA increased the protein expression levels of α-SMA, fibronectin and vimentin but significantly decreased the protein expression levels of E-cadherin (P<0.05). Overexpression of BMP-6 inhibited the migration of RPE cells induced by TGF-ß2 and prevented TGF-ß2 from affecting EMT-related biomarkers (P<0.05). CONCLUSION: BMP-6 prevents the EMT in RPE cells induced by TGF-ß2, which may provide a theoretical basis for the prevention and treatment of proliferative vitreoretinopathy.