Image smoothing method based on global gradient sparsity and local relative gradient constraint optimization.

Removing texture while preserving the main structure of an image is a challenging task. To address this, this paper propose an image smoothing method based on global gradient sparsity and local relative gradient constraints optimization. To reduce the interference of complex texture details, adopting a multi-directional difference constrained global gradient sparsity decomposition method, which provides a guidance image with weaker texture detail gradients. Meanwhile, using the luminance channel as a reference, edge-aware operator is constructed based on local gradient constraints. This operator weakens the gradients of repetitive and similar texture details, enabling it to obtain more accurate structural information for guiding global optimization of the image. By projecting multi-directional differences onto the horizontal and vertical directions, a mapping from multi-directional differences to bi-directional gradients is achieved. Additionally, to ensure the consistency of measurement results, a multi-directional gradient normalization method is designed. Through experiments, we demonstrate that our method exhibits significant advantages in preserving image edges compared to current advanced smoothing methods.

An Integrated Multi-omics prediction model for stroke recurrence based on Lnet transformer layer and dynamic weighting mechanism.

BACKGROUND AND OBJECTIVE: Stroke is a disease with high mortality and disability. Importantly, the fatality rate demonstrates a significant increase among patients afflicted by recurrent strokes compared to those experiencing their initial stroke episode. Currently, the existing research encounters three primary challenges. The first is the lack of a reliable, multi-omics image dataset related to stroke recurrence. The second is how to establish a high-performance feature extraction model and eliminate noise from continuous magnetic resonance imaging (MRI) data. The third is how to integration multi-omics data and dynamically weighted for different omics data. METHODS: We systematically compiled MRI and conventional detection data from a cohort comprising 737 stroke patients and established PSTSZC, a multi-omics dataset for predicting stroke recurrence. We introduced the first-ever Integrated Multi-omics Prediction Model for Stroke Recurrence, MPSR, which is based on ResNet, Lnet-transformer, LSTM and dynamically weighted DNN. The MPSR model comprises two principal modules, the Feature Extraction Module, and the Integrated Multi-Omics Prediction Module. In the Feature Extraction module, we proposed a novel Lnet regularization layer, which effectively addresses noise issues in MRI data. In the Integrated Multi-omics Prediction Module, we propose a dynamic weighted mechanism based on evaluators, which mitigates the noise impact brought about by low-performance omics. RESULTS: We compared seven single-omics models and six state-of-the-art multi-omics stroke recurrence models. The experimental results demonstrate that the MPSR model exhibited superior performance. The accuracy, AUROC, specificity, and sensitivity of the MPSR model can reach 0.96, 0.97, 1, and 0.94, respectively, which is higher than the results of contrast model. CONCLUSION: MPSR is the first available high-performance multi-omics prediction model for stroke recurrence. We assert that the MPSR model holds the potential to function as a valuable tool in assisting clinicians in accurately diagnosing individuals with a predisposition to stroke recurrence.

Traditional and Novel Organophosphate Esters in Plastic Greenhouse: Occurrence, Multimedia Migration, and Exposure Risk via Vegetable Consumption.

The migration and risk of organophosphate esters (OPEs) in agricultural air-soil-plant multimedia systems due to plastic film application remain unclear. This study investigates the multimedia distribution of traditional OPEs (TOPEs), novel OPEs (NOPEs), and their transformation products (POPEs) in plastic and solar greenhouses. The total concentration of OPE-associated contaminants in air and airborne particles ranged from 594 to 1560 pg/m3 and 443 to 15600 ng/g, respectively. Significant correlations between air OPE concentrations and those in polyolefin film (P < 0.01) indicate plastic film as the primary source. Contaminants were also found in soils (96.8-9630 ng/g) and vegetables (197-7540 ng/g). The primary migration pathway for NOPEs was particle dry deposition onto the soil and leaf, followed by plant accumulation. Leaf absorption was the main uptake pathway for TOPEs and POPEs, influenced by vegetable specific leaf surface area. Moreover, total exposure to OPE-associated contaminants via vegetable intake was assessed at 2250 ng/kg bw/day for adults and 2900 ng/kg bw/day for children, with an acceptable hazard index. However, a high ecological risk was identified for NOPE compounds (median risk quotient, 975). This study provides the first evidence of the multimedia distribution and potential threat posed by OPE-associated contaminants in agricultural greenhouses.

An updated meta-analysis of optimal medical therapy with or without invasive therapy in patients with stable coronary artery disease.

BACKGROUND: The efficacy of optimal medical therapy (OMT) with or without revascularization therapy in patients with stable coronary artery disease (SCAD) remains controversial. We performed a meta-analysis of randomized controlled trials (RCTs) that compared OMT with or without revascularization therapy for SCAD patients. METHODS: Studies were searched in PubMed, EMBASE, and the Cochrane Central Register of Clinical Trials from January 1, 2005, to December 30, 2023. The main efficacy outcome was a composite of all-cause death, myocadiac infarction, revascularization, and cerebrovascular accident. Results were pooled using random effects model and fixed effects model and are presented as odd ratios (ORs) with 95% confidence intervals (CI). RESULTS: Ten studies involving 12,790 participants were included. The arm of OMT with revascularization compared with OMT alone was associated with decreased risks for MACCE (OR 0.55 [95% CI 0.38-0.80], I²=93%, P = 0.002), CV death (OR 0.84 [95% CI 0.73-0.97], I²=36%, P = 0.02), revascularization (OR 0.32 [95% CI 0.20-0.50], I²=92%, P < 0.001), and MI (OR 0.85 [95% CI 0.76-0.96], I²=45%, P = 0.007). While there was no significant difference between OMT with revascularization and OMT alone in the odds of all-cause death (OR 0.94 [95% CI 0.84-1.05], I²=0%, P = 0.30). CONCLUSIONS: The current updated meta-analysis of 10 RCTs shows that in patients with SCAD, OMT with revascularization would reduce the risk for MACCE, cardiovascular death, and MI. However, the invasive strategy does not decrease the risks for all-cause mortality when comparing with OMT alone.

Scorch processing of rhubarb (Rheum tanguticum Maxim. ex Balf.) pyrolyzed anthraquinone glucosides into aglycones and improved the therapeutic effects on thromboinflammation via regulating the complement and coagulation cascades pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The pathophysiological mechanism of thromboinflammation involves the intricate interplay between the inflammatory responses and coagulation cascades. Rhubarb is frequently used in traditional Chinese medicine to treat thromboinflammatory diseases. The scorched rhubarb (prepared by stir-baking the dried raw rhubarb till it partly turns to charcoal) is believed to possess enhanced blood-cooling and stasis-removing functions compared to the raw rhubarb, thereby augmenting the therapeutic effects on thromboinflammation. AIM OF THE STUDY: This study aimed to explore the chemical and pharmacological foundations of the scorch processing of rhubarb in order to ensure and enhance the efficacy and safety of the scorched rhubarb for treating thromboinflammatory diseases. MATERIALS AND METHODS: The dried raw rhubarb pieces were subjected to stir-baking at 180 °C for 10∼80 min to obtain the rhubarbs with varying degrees of scorching. Typical ingredients present in rhubarb pieces and extracts were determined by high-performance liquid chromatography. The therapeutic effects of the raw and scorched rhubarb on thromboinflammation were evaluated using a rat model. Proteomics analysis was employed to screen potential biological pathways associated with thromboinflammation treatment by the raw and scorched rhubarb, which were further verified using a cell model. RESULTS: Morphological properties indicated that the rhubarb baked at 180 °C for 50 min in this research showed the optimal degree of scorching. Compared to the raw rhubarb, the properly scorched rhubarb exhibited lower levels of anthraquinone glucosides, higher levels of anthraquinone aglycones, superior anti-thromboinflammatory effects, and no purgative side effects. Proteomics analysis revealed that the complement and coagulation cascades pathway played a significant role in mediating the therapeutic effects of the raw and scorched rhubarb on thromboinflammation. Furthermore, it was found that anthraquinone aglycones were more effective than their glucoside counterparts in restoring the impaired vascular endothelial cells as well as regulating the complement and coagulation cascades pathway. CONCLUSIONS: Proper scorch processing may augment the therapeutic effects of rhubarb on thromboinflammation via relieving inflammation and oxidative stress, repairing vascular endothelial cells, restoring coagulation cascades and blood rheology, and regulating some other biological processes. This may be partly caused by the scorch-induced thermolysis of anthraquinone glucosides into their aglycone counterparts that seemed to perform better in regulating the complement and coagulation cascades pathway.

SERPINB7 Deficiency Increases Legumain Activity and Impairs the Epidermal Barrier in Nagashima-type Palmoplantar Keratoderma.

Nagashima-type palmoplantar keratoderma (NPPK) is an autosomal recessive genodermatosis caused by loss-of-function variants in SERPINB7 and is the most prevalent form of inherited palmoplantar keratodermas among Asians. However, there is currently no effective therapy for NPPK because its pathogenesis remains unclear. In this study, Serpinb7-/- mice were generated and spontaneously developed a disrupted skin barrier, which was further exacerbated by acetone-ether-water treatment. The skin of these Serpinb7-/- mice showed weakened cytoskeletal proteins. Additionally, SERPINB7 deficiency consistently led to decreased epidermal differentiation in a three-dimensional human epidermal model. We also demonstrated that SERPINB7 was an inhibitory serpin that mainly inhibited the protease legumain. SERPINB7 bound directly with legumain and inhibited legumain activity both in vitro and in vivo. Furthermore, we found that SERPINB7 inhibited legumain in a 'protease-substrate' manner and identified the cleavage sites of SERPINB7 as Asn71 and Asn343. Overall, we found that SERPINB7 showed the nature of a cysteine protease inhibitor, and identified legumain as a key target protease of SERPINB7. Loss of SERPINB7 function led to overactivation of legumain, which might disrupt cytoskeletal proteins, contributing to the impaired skin barrier in NPPK. These findings may lead to the development of therapeutic strategies for NPPK.

Design, synthesis and biological activity of oxyevodiamine-based histone deacetylase 6 inhibitors.

Histone deacetylase 6 (HDAC6) was a potential target for Alzheimer's disease (AD). In this study, a series of novel oxyevodiamine-based HDAC6 inhibitors with a variety of linker moieties were designed, synthesized and evaluated. Compound 12 with a benzyl linker was identified as a high potent and selective HDAC6 inhibitor. It inhibited HDAC6 with an IC50 value of 6.2 nM and was more than 200 fold selectivity over HDAC1. It also had lower cytotoxicity and higher anti-H2O2 activity in vitro comparing with other derivatives. Compound 12 might be a good lead as novel HDAC6 inhibitor for the treatment of AD.

Prevalence and Evolutionary Characteristics of Bovine Coronavirus in China.

Bovine coronavirus (BCoV), bovine rotavirus, bovine viral diarrhea virus, and bovine astrovirus are the most common intestinal pathogenic viruses causing diarrhea in cattle. We collected 1646 bovine fecal samples from January 2020 to August 2023. BCoV was the major pathogen detected, with a positive rate of 34.02% (560/1646). Of the 670 diarrheal samples and 976 asymptomatic samples, 209 and 351 were BCoV-positive, respectively. Studying the relevance of diarrhea associated with BCoV has shown that the onset of diarrheal symptoms post-infection is strongly correlated with the cattle's age and may also be related to the breed. We amplified and sequenced the hemagglutinin esterase (HE), spike protein, and whole genomes of the partially positive samples and obtained six complete HE sequences, seven complete spike sequences, and six whole genomes. Molecular characterization revealed that six strains were branched Chinese strains, Japanese strains, and partial American strains from the GⅡb subgroup. Strains HBSJZ2202 and JSYZ2209 had four amino acid insertions on HE. We also analyzed ORF1a and found disparities across various regions within GIIb, which were positioned on separate branches within the phylogenetic tree. This work provides data for further investigating the epidemiology of BCoV and for understanding and analyzing BCoV distribution and dynamics.

Neuro-BERT: Rethinking Masked Autoencoding for Self-Supervised Neurological Pretraining.

Deep learning associated with neurological signals is poised to drive major advancements in diverse fields such as medical diagnostics, neurorehabilitation, and brain-computer interfaces. The challenge in harnessing the full potential of these signals lies in the dependency on extensive, high-quality annotated data, which is often scarce and expensive to acquire, requiring specialized infrastructure and domain expertise. To address the appetite for data in deep learning, we present Neuro-BERT, a self-supervised pre-training framework of neurological signals based on masked autoencoding in the Fourier domain. The intuition behind our approach is simple: frequency and phase distribution of neurological signals can reveal intricate neurological activities. We propose a novel pre-training task dubbed Fourier Inversion Prediction (FIP), which randomly masks out a portion of the input signal and then predicts the missing information using the Fourier inversion theorem. Pre-trained models can be potentially used for various downstream tasks such as sleep stage classification and gesture recognition. Unlike contrastive-based methods, which strongly rely on carefully hand-crafted augmentations and siamese structure, our approach works reasonably well with a simple transformer encoder with no augmentation requirements. By evaluating our method on several benchmark datasets, we show that Neuro-BERT improves downstream neurological-related tasks by a large margin.

A novel virus-like particles vaccine induces broad immune protective against deltacoronavirus in piglets.

Coronaviruses (CoVs) comprise a group of important human and animal pathogens that threaten public health because of their interspecies transmission potential to humans. However, virus-like particles (VLPs) constitute versatile tools in CoVs vaccine development due to their favorable immunological characteristics. Here, we engineered the VLPs composed of the spike (S), membrane (M), and envelope (E) structural proteins of the Porcine deltacoronavirus (PDCoV) and examined their immune responses in mice. Neutralization assays and flow Cytometry demonstrated that PDCoV VLPs induced highly robust neutralizing antibodies (NAbs) and elicited cellular immunity. To assess the protective efficacy of VLPs in newborn piglets, pregnant sows received vaccinations with either a PDCoV-inactivated vaccine or VLPs at 40 and 20 days before delivery. Five days post-farrowing, piglets were orally challenged with the PDCoV strain. Severe diarrhea, high viral RNA copies, and substantial intestinal villus atrophy were detected in piglets born to unimmunized sows. However, piglets from sows immunized with VLPs exhibited high NAbs titers and markedly reduced microscopic damage to the intestinal tissues, with no piglet showing diarrhea. Hence, the results indicate that the VLPs are a potential clinical candidate for PDCoV vaccination, while the strategy may serve as a platform for developing other coronavirus vaccines.

Renal toxicity of Aconitum plants? A study based on a new mass spectrometry scanning strategy and computer virtual screening.

BACKGROUND: Radix Aconiti Lateralis (Fuzi), a mono-herbal preparation of Aconitum herbs in the genus Aconitum, is commonly used in traditional Chinese medicine (TCM) to treat critical illnesses. The curative effect of Fuzi is remarkable. However, the toxic effects of Fuzi are still a key clinical focus, and the substances inducing nephrotoxicity are still unclear. Therefore, this study proposes a research model combining "in vitro and in vivo component mining-virtual multi-target screening-active component prediction-literature verification" to screen potential nephrotoxic substances rapidly. METHOD: The UHPLC-Q-Exactive-Orbitrap MS analysis method was used for the correlation analysis of Fuzi's in vitro-in vivo chemical substance groups. On this basis, the key targets of nephrotoxicity were screened by combining online disease databases and a protein-protein interaction (PPI) network. The computer screening technique was used to verify the binding mode and affinity of Fuzi's components with nephrotoxic targets. Finally, the potential material basis of Fuzi-induced nephrotoxicity was screened. RESULTS: Eighty-one Fuzi components were identified. Among them, 35 components were absorbed into the blood. Based on the network biology method, 21 important chemical components and three potential key targets were screened. Computer virtual screening revealed that mesaconine, benzoylaconine, aconitine, deoxyaconitine, hypaconitine, benzoylhypaconine, benzoylmesaconine, and hypaconitine may be potential nephrotoxic substances of Fuzi. CONCLUSIONS: Fuzi may interact with multiple components and targets in the process of inducing nephrotoxicity. In the future, experiments can be designed to explore further. This study provides a reference for screening Fuzi nephrotoxic components and has certain significance for the safe use of Fuzi.

Efficacy of submental island flap closing advanced mandibular MRONJ lesion in malignancy patients.

OBJECTIVE: This study evaluated the effectiveness of a submental island flap in closing advanced mandibular medication-related osteonecrosis of the jaw (MRONJ) wounds in patients with malignant tumors. SUBJECTS AND METHODS: A total of 85 patients with stage II and III MRONJ of mandible with malignant tumor as their primary disease were retrospectively analyzed. All patients underwent surgical treatment, and the soft tissue wound closure was performed either with a submental island flap (SIF) or mucoperiosteal flap (MF). Univariate and multifactorial models were applied to analyze the factors influencing patients' prognosis. RESULTS: Univariate analysis (p = 0.004, OR 0.075-0.575, 95% CI) and binary logistic regression (p = 0.017, OR 0.032-0.713, 95% CI) suggested that the surgical prognosis of SIF wound closure was significantly better than that of MF. CONCLUSION: Closure of wound after resection of mandibular MRONJ lesions in patients with malignant tumors using SIF had a better clinical prognosis compared with MF.

Increasing expression of dual-specificity phosphatase 12 mitigates oxygen-glucose deprivation/reoxygenation-induced neuronal apoptosis and inflammation through inactivation of the ASK1-JNK/p38 MAPK pathway.

Dual-specificity phosphatase 12 (DUSP12) is abnormally expressed under various pathological conditions and plays a crucial role in the pathological progression of disorders. However, the role of DUSP12 in cerebral ischaemia/reperfusion injury has not yet been investigated. This study explored the possible link between DUSP12 and cerebral ischaemia/reperfusion injury using an oxygen-glucose deprivation/reoxygenation (OGD/R) model. Marked decreases in DUSP12 levels have been observed in cultured neurons exposed to OGD/R. DUSP12-overexpressed neurons were resistant to OGD/R-induced apoptosis and inflammation, whereas DUSP12-deficient neurons were vulnerable to OGD/R-evoked injuries. Further investigation revealed that DUSP12 overexpression or deficiency affects the phosphorylation of apoptosis signal-regulating kinase 1 (ASK1), c-Jun NH2-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) in neurons under OGD/R conditions. Moreover, blockade of ASK1 diminished the regulatory effect of DUSP12 deficiency on JNK and p38 MAPK activation. In addition, DUSP12-deficiency-elicited effects exacerbating neuronal OGD/R injury were reversed by ASK1 blockade. In summary, DUSP12 protects against neuronal OGD/R injury by reducing apoptosis and inflammation through inactivation of the ASK1-JNK/p38 MAPK pathway. These findings imply a neuroprotective function for DUSP12 in cerebral ischaemia/reperfusion injury.

Clinicopathological and molecular genetic analysis of 13 cases of primary retroperitoneal Ewing sarcoma.

Retroperitoneal Ewing sarcomas (RES) are very rare and mostly described in case reports. The purpose of this study was to retrospectively analyze the clinicopathology, molecular characteristics, biological behavior, and therapeutic information of 13 cases of primary RES with immunohistochemical staining, fluorescence in situ hybridization, RT-PCR and NGS sequencing detection techniques. The thirteen patients included eight males and five females with a mean age of 34 years. Morphologically, the tumors were comprised of small round or epithelial-like cells with vacuolated cytoplasm (6/13,46 %) arranged in diffuse, nested (8/13,62 %) and perivascular (7/13,54 %) patterns. Unusual morphologic patterns, such as meningioma-like swirling structures and sieve-like structures were relatively novel findings. Immunohistochemical studies showed CD99 (12/13; 92 %), CD56 (11/13; 85 %), NKX2.2 (9/13; 69 %), PAX7 (10/11;91 %) and CD117(6/9;67 %) to be positive.12 cases (92 %) demonstrated EWSR1 rearrangement and 3 cases displayed EWSR1::FLI1 fusion by FISH. ERCC4 splice-site variant, a novel pathogenic variant, was discovered for the first time via RNA sequencing. With a median follow-up duration of 14 months (6 to 79 months), 8/13 (62 %) patients died, while 5/13(38 %) survived. Three cases recurred, and five patients developed metastasis to the liver (2 cases), lung (2 cases) and bone (1 case). RES is an aggressive, high-grade tumor, prone to multiple recurrences and metastases, with distinctive morphologic, immunohistochemical, and molecular genetic features. ERCC4 splicing mutation, which is a novel pathogenic variant discovered for the first time, with possible significance for understanding the disease, as well as the development of targeted drugs.

Time-to-go based three-dimensional multi-missile spatio-temporal cooperative guidance law: A novel approach for maneuvering target interception.

This research presents a novel approach called 'Time-to-target-based multi-missile spatio-temporal cooperative guidance' This approach enables the simultaneous guidance of multiple missiles, allowing them to intercept a maneuvering target from different terminal intercept angles to maximize damage. The article introduces a finite-time optimal cooperative guidance technique to reduce the load on missile engines in the line-of-sight (LOS) direction. It proposes a time-varying sliding mode guidance scheme, which is parameterized by the remaining flight time, for both longitudinal and lateral LOS directions. The scheme helps prevent excessive initial acceleration in the longitudinal and lateral LOS directions while ensuring intercept angle constraints. The time-varying cooperative guidance law proposed in this study enables the simultaneous interception of a maneuvering target with different terminal intercept angles at the moment of terminal intercept. The numerical simulation results indicate that the multi-missile spatio-temporal cooperative guidance method is effective, superior, and robust. The method enables multiple missiles to achieve the minimum acceptable intercept distance at different terminal intercept angles while optimizing fuel in the LOS direction.

Disrupted mitochondrial transcription factor A expression promotes mitochondrial dysfunction and enhances ocular surface inflammation by activating the absent in melanoma 2 inflammasome.

PURPOSE: Severe dry eye disease causes ocular surface damage, which is highly associated with mitochondrial dysfunction. Mitochondrial transcription factor A (TFAM) is essential for packaging mitochondrial DNA (mtDNA) and is crucial for maintaining mitochondrial function. Herein, we aimed to explore the effect of a decreased TFAM expression on ocular surface damage. METHODS: Female C57BL/6 mice were induced ocular surface injury by topical administrating benzalkonium chloride (BAC). Immortalized human corneal epithelial cells (HCECs) were stimulated by tert-butyl hydroperoxide (t-BHP) to create oxidative stress damage. HCECs with TFAM knockdown were established. RNA sequencing was employed to analyze the whole-genome expression. Mitochondrial changes were measured by transmission electron microscopy, Seahorse metabolic flux analysis, mitochondrial membrane potential, and mtDNA copy number. TFAM expression and inflammatory cytokines were determined using RT-qPCR, immunohistochemistry, immunofluorescence, and immunoblotting. RESULTS: In both the corneas of BAC-treated mice and t-BHP-induced HCECs, we observed impaired TFAM expression, accompanied by mitochondrial structure and function defects. TFAM downregulation in HCECs suppressed mitochondrial respiratory capacity, reduced mtDNA content, induced mtDNA leakage into the cytoplasm, and led to inflammation. RNA sequencing revealed the absent in melanoma 2 (AIM2) inflammasome was activated in the corneas of BAC-treated mice. The AIM2 inflammasome activation was confirmed in TFAM knockdown HCECs. TFAM knockdown in t-BHP-stimulated HCECs aggravated mitochondrial dysfunction and the AIM2 inflammasome activation, thereby further triggering the secretion of inflammatory factors such as interleukin (IL) -1ß and IL-18. CONCLUSIONS: TFAM reduction impaired mitochondrial function, activated AIM2 inflammasome and promoted ocular surface inflammation, revealing an underlying molecular mechanism for ocular surface disorders.

The effects of BDNF rs6265 and FGF21 rs11665896 polymorphisms on alcohol use disorder-related impulsivity in Han Chinese adults.

Introduction: Patients with alcohol use disorder (AUD) often experience repeated withdrawal. Impulsivity is the most relevant factor influencing successful withdrawal. Brain-derived neurotrophic factor (BNDF) and fibroblast growth factor 21 (FGF21) are associated with impulsivity. Previous studies on the differential effects of BDNF or FGF21 on impulsivity have focused on single-gene effects and have inconsistent results. We aim to investigate the effects of BDNF rs6265 and FGF21 rs11665896, individually and together, on impulsivity during alcohol withdrawal in patients with AUD. Methods: We recruited 482 adult Han Chinese males with AUD and assessed their impulsivity using the Barratt Impulsivity Scale. Genomic DNA was extracted and genotyped from peripheral blood samples. Statistical analysis was conducted on the data. Results: The T-test and 2 × 2 analysis of variance were used to investigate the effects of the genes on impulsivity. There was a significant BDNF × FGF21 interaction on no-planning impulsiveness (F = 9.15, p = 0.003, η2p = 0.03). Simple main effects analyses and planned comparisons showed that BDNF rs6265 A allele × FGF21 rs11665896 T allele was associated with higher no-planning impulsiveness. Finally, hierarchical regression analyses revealed that only the interaction of BDNF and FGF21 accounted for a significant portion of the variance in no-planning impulsiveness. Conclusion and significance: The combination of BDNF rs6265 A allele and FGF21 rs11665896 T allele may increase impulsivity and discourage alcohol withdrawal. Our study provides a possible genetic explanation for the effects of associated impulsivity in patients with AUD from the perspective of gene-gene interactions.

Imidazole functionalized photo-crosslinked aliphatic polycarbonate drug-eluting coatings on zinc alloys for osteogenesis, angiogenesis, and bacteriostasis in bone regeneration.

Zinc (Zn) alloys have demonstrated significant potential in healing critical-sized bone defects. However, the clinical application of Zn alloys implants is still hindered by challenges including excessive release of zinc ions (Zn2+), particularly in the early stage of implantation, and absence of bio-functions related to complex bone repair processes. Herein, a biodegradable aliphatic polycarbonate drug-eluting coating was fabricated on zinc-lithium (Zn-Li) alloys to inhibit Zn2+ release and enhance the osteogenesis, angiogenesis, and bacteriostasis of Zn alloys. Specifically, the photo-curable aliphatic polycarbonates were co-assembled with simvastatin and deposited onto Zn alloys to produce a drug-loaded coating, which was crosslinked by subsequent UV light irradiation. During the 60 days long-term immersion test, the coating showed distinguished stable drug release and Zn2+ release inhibition properties. Benefiting from the regulated release of Zn2+ and simvastatin, the coating facilitated the adhesion, proliferation, and differentiation of MC3T3-E1 cells, as well as the migration and tube formation of EA.hy926 cells. Astonishingly, the coating also showed remarkable antibacterial properties against both S. aureus and E. coli. The in vivo rabbit critical-size femur bone defects model demonstrated that the drug-eluting coating could efficiently promote new bone formation and the expression of platelet endothelial cell adhesion molecule-1 (CD31) and osteocalcin (OCN). The enhancement of osteogenesis, angiogenesis, and bacteriostasis is achieved by precisely controlling of the released Zn2+ at an appropriate level, as well as the stable release profile of simvastatin. This tailored aliphatic polycarbonate drug-eluting coating provides significant potential for clinical applications of Zn alloys implants.

Zero-shot reconstruction of ocean sound speed field tensors: A deep plug-and-play approach.

Reconstructing a three-dimensional ocean sound speed field (SSF) from limited and noisy measurements presents an ill-posed and challenging inverse problem. Existing methods used a number of pre-specified priors (e.g., low-rank tensor and tensor neural network structures) to address this issue. However, the SSFs are often too complex to be accurately described by these pre-defined priors. While utilizing neural network-based priors trained on historical SSF data may be a viable workaround, acquiring SSF data remains a nontrivial task. This work starts with a key observation: Although natural images and SSFs admit fairly different characteristics, their denoising processes appear to share similar traits-as both remove random components from more structured signals. This observation allows us to incorporate deep denoisers trained using extensive natural images to realize zero-shot SSF reconstruction, without any extra training or network modifications. To implement this idea, an alternating direction method of multipliers (ADMM) algorithm using such a deep denoiser is proposed, which is reminiscent of the plug-and-play scheme from medical imaging. Our plug-and-play framework is tailored for SSF recovery such that the learned denoiser can be simultaneously used with other handcrafted SSF priors. Extensive numerical studies show that the new framework largely outperforms state-of-the-art baselines, especially under widely recognized challenging scenarios, e.g., when the SSF samples are taken as tensor fibers. The code is available at https://github.com/OceanSTARLab/DeepPnP.