Explore the vast range of titles available.

X-linked inhibitor of apoptosis-associated factor 1 (XAF1) is a pro-apoptotic tumor suppressor that is frequently inactivated in multiple human cancers. However, its candidacy as a suppressor in the pathogenesis of breast cancer remains undefined. Here, we report that XAF1 acts as a molecular switch in estrogen (E2)-mediated cell-fate decisions favoring apoptosis over cell proliferation. XAF1 promoter hypermethylation is observed predominantly in estrogen receptor α (ERα)-positive versus ERα-negative tumor cells and associated with attenuated apoptotic response to E2. XAF1 is activated by E2 through a G protein-coupled estrogen receptor-mediated non-genomic pathway and induces ERα degradation and apoptosis while it is repressed by ERα for E2 stimulation of cell proliferation. The XAF1-ERα mutual antagonism dictates the outcomes of E2 signaling and its alteration is linked to the development of E2-resistant tumors. Mechanistically, XAF1 destabilizes ERα through the assembly of breast cancer-associated gene 1 (BRCA1)-mediated destruction complex. XAF1 interacts with ERα and BRCA1 via the zinc finger (ZF) domains 5/6 and 4, respectively, and the mutants lacking either of these domains fail to drive ERα ubiquitination and apoptosis. E2-induced regression of XAF1 +/+ tumors is abolished by XAF1 depletion while XAF1 −/− tumors recover E2 response by XAF1 restoration. XAF1 and ERα expression show an inverse correlation in primary breast tumors, and XAF1 expression is associated with the overall survival of patients with ERα-positive but not ERα-negative cancer. Together, this study uncovers an important role for the XAF1-ERα antagonism as a linchpin to govern E2-mediated cell-fate decisions, illuminating the mechanistic consequence of XAF1 alteration in breast tumorigenesis.

Research on semantic segmentation for remote sensing road scenes advanced significantly, driven by autonomous driving technology. However, motion blur from camera or subject movements hampers segmentation performance. To address this issue, we propose a knowledge distillation-based semantic segmentation network (KDS-Net) that is robust to motion blur, eliminating the need for image restoration networks. KDS-Net leverages innovative knowledge distillation techniques and edge-enhanced segmentation loss to refine edge regions and improve segmentation precision across various receptive fields. To enhance the interpretability of segmentation quality under motion blur, we incorporate fractal dimension estimation to quantify the geometric complexity of class-specific regions, allowing for a structural assessment of predictions generated by the proposed knowledge distillation framework for autonomous driving. Experiments on well-known motion-blurred remote sensing road scene datasets (CamVid and KITTI) demonstrate mean IoU scores of 72.42% and 59.29%, respectively, surpassing state-of-the-art methods. Additionally, the lightweight KDS-Net (21.44 M parameters) enables real-time edge computing, mitigating data privacy concerns and communication overheads in internet of vehicles scenarios.

Dysbiosis of the sinus microbiome affects the pathophysiology of chronic rhinosinusitis with nasal polyps (CRSwNPs). We investigated whether the sinus microbiota in CRSwNPs is associated with eosinophilic inflammation, especially in relation to innate lymphoid cells (ILCs), prognosis, and serum extracellular vesicles (EVs). Middle meatal swabs and serum from 31 CRSwNPs patients and six healthy controls were analyzed by 16S ribosomal RNA sequencing. ILC2s and cytokines from sinonasal tissues were measured by flow cytometry and ELISA, respectively. The relative abundances (RAs) of bacteria were compared based on eosinophilic inflammation and surgical outcome. The correlations between sinus bacteria and ILC2s, cytokines, and serum EVs were analyzed. The compositions of sinus bacteria were different between groups at the genus level. In eosinophilic CRSwNPs patients, the RA of Anaerococcus was significantly decreased (P = 0.010), whereas that of Lachnoclostridium was significantly increased (P = 0.038) compared with that in controls. The RA of Lachnoclostridium showed a significant positive correlation with interleukin (IL)-5-producing ILC2 populations (R = 0.340, P = 0.049), whereas the RA of Anaerococcus showed a negative correlation with IL-5-producing ILC2 populations (R = −0.332, P = 0.055). The RAs of Corynebacterium, Anaerococcus, and Tepidimonas were significantly decreased in patients with suboptimal outcomes compared with those in patients with optimal outcomes and control subjects. Some sinus bacteria and serum EVs showed positive correlations. CRSwNPs patients showed distinct microbiota compositions based on eosinophilic inflammation in relation to ILC2s and surgical outcome. These findings support a relationship between the microbiota and the host immune response in CRSwNPs.Sinus disease: nasal bacteria linked to manifestations of chronic diseaseMicrobes living in the sinonasal cavity seem to affect the immune responses and clinical outcomes of patients with an inflammatory disease that can cause lasting pain, pressure, and swelling in the sinuses. Ji Heui Kim from the Asan Medical Center in Seoul, South Korea, and colleagues collected nasal swabs and blood from 31 people suffering from chronic rhinosinusitis with nasal polyps and from six healthy control individuals. They identified several specific bacterial groups whose presence or absence was associated with the abundance of certain white blood cell populations, a sign of inflammation. Some of these groups were linked to patient outcomes after nasal surgery but additional groups were also observed. The findings could help lead to new treatment strategies or diagnostic biomarkers for patients with this sinus disorder.

X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1) is a tumor suppressor that is frequently inactivated in many human cancers. However, the molecular mechanism underlying its growth-inhibitory function remains largely unknown. Here, we report that XAF1 forms a positive feedback loop with p53 and acts as a molecular switch in p53-mediated cell-fate decisions favoring apoptosis over cell-cycle arrest. XAF1 binds directly to the N-terminal proline-rich domain of p53 and thus interferes with E3 ubiquitin ligase MDM2 binding and ubiquitination of p53. XAF1 stimulates homeodomain-interacting protein kinase 2 (HIPK2)-mediated Ser-46 phosphorylation of p53 by blocking E3 ubiquitin ligase Siah2 interaction with and ubiquitination of HIPK2. XAF1 also steps up the termination of p53-mediated cell-cycle arrest by activating zinc finger protein 313 (ZNF313), a p21 ᵂᴬF¹-targeting ubiquitin E3 ligase. XAF1 interacts with p53, Siah2, and ZNF313 through the zinc finger domains 5, 6, and 7, respectively, and truncated XAF1 isoforms preferentially expressed in cancer cells fail to form a feedback loop with p53. Together, this study uncovers a novel role for XAF1 in p53 stress response, adding a new layer of complexity to the mechanisms by which p53 determines cell-fate decisions. Significance Epigenetic inactivation of X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1) is frequently observed in multiple human malignancies. However, the mechanisms underlying its tumor-suppression function remain largely undefined. Here, we identify XAF1 as a positive feedback regulator of p53, which directs the apoptotic switch of p53 signaling. As a unique transcription target of p53 in signaling apoptosis, XAF1 acts as a competitor of E3 ubiquitin ligase MDM2 in binding to p53 and thus disrupts the p53–MDM2 regulatory loop. Moreover, XAF1 appears to promote homeodomain-interacting protein kinase 2 (HIPK2)-mediated p53 phosphorylation by interrupting HIPK2-targeting function of E3 ubiquitin ligase Siah2 and promotes zinc finger protein 313 (ZNF313)-induced p21 ᵂᴬF¹ ubiquitination. XAF1 thus represents one critical regulator of p53’s cell-fate decision function, suggesting that restoring the p53–XAF1 feedback loop could be an attractive avenue for the therapeutic intervention of malignant tumor progression.

NORE1A (RASSF5) is a tumor suppressor of the Ras-association domain family (RASSF) that is commonly inactivated in multiple human cancers. However, the molecular mechanism underlying its growth inhibition function remains largely undefined. Here we report that NORE1A antagonizes tumor necrosis factor receptor I (TNFRI) through the assembly of ITCH-mediated destruction complex to suppress TNF-NF-κB signaling and tumorigenesis. Moreover, NORE1A is identified as a transcription target of NF-κB, which directs an apoptotic switch of TNF effect by blocking ITCH interaction with and ubiquitination of BAX. Mechanistically, NORE1A binds directly to TNFRI and ITCH via the C1 and PPXY domains, respectively to facilitate the formation of ITCH-mediated destruction complex followed by ubiquitination-mediated lysosomal degradation of TNFRI. Through this function, NORE1A suppresses TNF-induced NF-κB-mediated transcription of pro-inflammatory and tumor-promoting genes, epithelial-to-mesenchymal transition, invasion and migration of tumor cells, and also debilitates tumor cell activation of macrophage and fibroblast. While NORE1A suppresses TNF receptor-mediated apoptosis, it activates TNF-induced apoptosis through BAX activation by protecting BAX from ITCH binding and ubiquitination. Cytotoxic response to TNF is substantially attenuated in NORE1A-depleted cells and tumors, and NORE1A-induced tumor regression is highly impeded in BAX-depleted tumors. An inverse correlation is shown between NORE1A and TNFRI expression in both cancer cell lines and primary tumors, and NORE1A effect on survival of cancer patients is strongly associated with expression status of ITCH. Collectively, this study uncovers that NORE1A directs a substrate switch of ITCH favoring TNFRI over BAX to terminate TNF signaling and accelerate apoptosis, illuminating the mechanistic consequence of NORE1A inactivation in tumorigenesis.

Person re-identification (Re-ID) using infrared surveillance cameras has attracted increasing attention due to its robustness under low-light conditions. However, infrared images generally suffer from a low spatial resolution, which degrades Re-ID performance. To address this issue, this study proposes a part attention and contrastive loss-based super-resolution reconstruction network (PCSR-Net) and a unified infrared-only Re-ID framework. The proposed PCSR-Net consists of a correlation-based super-resolution reconstruction network (CoSR-Net), a feature extractor for Re-ID, and a part attention mechanism that estimates the importance of different body regions. In addition, contrastive loss and part-aware reconstruction loss are incorporated to guide the super-resolution process toward identity-discriminative representations. Experimental results on DBPerson-Recog-DB1 and SYSU-MM01 demonstrate that the proposed method outperforms state-of-the-art approaches in terms of the equal error rate (EER), mean average precision (mAP), and rank-1 accuracy, validating its effectiveness for infrared-based person Re-ID.

The accurate classification of plant diseases is vital for global food security, as diseases can cause major yield losses and threaten sustainable and precision agriculture. The classification of plant diseases in low-light noisy environments is crucial because crops can be continuously monitored even at night. Important visual cues of disease symptoms can be lost due to the degraded quality of images captured under low-illumination, resulting in poor performance of conventional plant disease classifiers. However, researchers have proposed various techniques for classifying plant diseases in daylight, and no studies have been conducted for low-light noisy environments. Therefore, we propose a novel model for classifying plant diseases from low-light noisy images called dilated pixel attention network (DPA-Net). DPA-Net uses a pixel attention mechanism and multi-layer dilated convolution with a high receptive field, which obtains essential features while highlighting the most relevant information under this challenging condition, allowing more accurate classification results. Additionally, we performed fractal dimension estimation on diseased and healthy leaves to analyze the structural irregularities and complexities. For the performance evaluation, experiments were conducted on two public datasets: the PlantVillage and Potato Leaf Disease datasets. In both datasets, the image resolution is 256 × 256 pixels in joint photographic experts group (JPG) format. For the first dataset, DPA-Net achieved an average accuracy of 92.11% and harmonic mean of precision and recall (F1-score) of 89.11%. For the second dataset, it achieved an average accuracy of 88.92% and an F1-score of 88.60%. These results revealed that the proposed method outperforms state-of-the-art methods. On the first dataset, our method achieved an improvement of 2.27% in average accuracy and 2.86% in F1-score compared to the baseline. Similarly, on the second dataset, it attained an improvement of 6.32% in average accuracy and 6.37% in F1-score over the baseline. In addition, we confirm that our method is effective with the real low-illumination dataset self-constructed by capturing images at 0 lux using a smartphone at night. This approach provides farmers with an affordable practical tool for early disease detection, which can support crop protection worldwide.

The objective of this study was to evaluate the clinical outcome of ventral slot decompression and rehabilitation therapy in dogs with cervical intervertebral disc herniation (IVDH). Surgical decompression was performed in dogs with IVDH using the ventral slot procedure. After surgery, physiotherapeutic rehabilitation consisted of a combination of electrotherapy, infrared therapy and mechanical massage; treadmill exercise was started when the animal could stand up. A total of 58 dogs were selected from the hospital and included in two groups: rehabilitated group (RG, n = 34) and non-rehabilitated group (NRG, n = 24). Dogs of each group were subdivided into five groups based on a pre-operative clinical grading system. Grade 1 designated spinal pain only, grade 2 designated ambulatory paraparesis, grade 3 designated non-ambulatory paraparesis, grade 4 designated paraplegia with deep-pain perception intact and grade 5 designated paraplegia without deep-pain perception. Post-operative changes of both groups were evaluated and compared, including time until unassisted standing and walking after surgery and the success rate. Overall, 79.41% (27/34) of dogs had a successful neurologic outcome in the RG group, which was significantly (P < 0.05) higher than the NRG group 62.50% (15/24). Interestingly, the success rate differed when the preoperative grading system was considered. The success rates of grades 1, 2, 3, 4 and 5 were 100% (9/9), 100% (7/7), 75% (3/4), 53.85% (7/13) and 100% (1/1), respectively, in the rehabilitated groups, whereas in the non-rehabilitated groups success rates were 100% (5/5), 83.33% (5/6), 60.00% (3/5), 28.57% (2/7) and 0% (0/1), respectively. The differences in success rates between the two groups according to grading were 0, 16.67, 15, 25.57 and 100%, respectively. The proposed rehabilitation therapy after surgical decompression of cervical IVDH can improve the success rate when the preoperative pathological condition is severe.

Nocardiosis, a rare infectious disease in dogs and cats, is caused by Gram-positive aerobic actinomycetes of the genus Nocardia. A one-year-old castrated male Great Dane was presented with clinical signs of an ulcerated nodule on the right ear, which was observed after two weeks of treatment with cyclosporine and prednisolone due to idiopathic hepatitis. Cytological examination revealed pyogranulomatous inflammatory cells and blanched filamentous rods. To detect infectious agents, serosanguinous discharge of the nodule was subjected to bacterial and fungal cultures. For phenotyping of the infectious agents, colonies on blood agar culture plates were further analyzed by matrix-assisted laser desorption ionization (MALDI)-time-of-flight (TOF) mass spectrometry (VITEK MS). The MALDI-TOF spectra were identified as N. africana. Thus, the present case was diagnosed as cutaneous nocardiosis. The skin lesions of ulcerated nodules with fistulous tracts were gradually resolved by the administration of meropenem (8 mg/kg TID, IV) and doxycycline (5 mg/kg BID, PO). Although complete resolution of the skin lesions was observed on day 91 after the initial presentation, single administration of doxycycline was continued until day 198 after the initial presentation to prevent recurrence. To the best of our knowledge, this is the first report of Nocardia africana infection in a dog. In addition, our results show that MALDI-TOF mass spectrometry analysis could be a useful tool for the detection of Nocardia. spps.

Fog, freezing rain, and snow (melt) quickly condense on road surfaces, forming black ice that is difficult to identify and causes major accidents on highways. As a countermeasure to prevent icing car accidents, it is necessary to predict the amount and location of black ice. This study advanced previous models through machine learning and multi-sensor-verified results. Using spatial (hill shade, river system, bridge, and highway) and meteorological (air temperature, cloudiness, vapour pressure, wind speed, precipitation, snow cover, specific heat, latent heat, and solar radiation energy) data from the study area (Suncheon–Wanju Highway in Gurye-gun, Jeollanam-do, South Korea), the amount and location of black ice were modelled based on system dynamics to predict black ice and then simulated with a geographic information system in units of square metres. The intermediate factors calculated as input factors were road temperature and road moisture, modelled using a deep neural network (DNN) and numerical methods. Considering the results of the DNN, the root mean square error was improved by 148.6 % and reliability by 11.43 % compared to a previous study (linear regression). Based on the model results, multiple sensors were buried at four selected points in the study area. The model was compared with sensor data and verified with the upper-tailed test (with a significance level of 0.05) and fast Fourier transform (freezing does not occur when frequency = 0.00001 Hz). Results of the verified simulation can provide valuable data for government agencies like road traffic authorities to prevent traffic accidents caused by black ice.