Clinical and genetic characteristics in lymphoma patients with a second solid malignancy

Diagnosis and treatment of multiple primary malignancies are becoming a new challenge in clinical practice worldwide. The present study aimed to characterize the clinical and genetic features of multiple primary malignancies in patients with synchronous or metachronous lymphoma and another solid tumor. We retrospectively analyzed 11 cases with lymphoma and another solid tumor. The germline mutations in plasma cell-free DNA samples and somatic mutations in lymphoma and solid tumor tissue samples were identified using targeted next-generation sequencing. In the 11 lymphoma patients, the most common type of concurrent solid tumor was colon adenocarcinoma (case 3, 5, 9 11) followed by papillary thyroid carcinoma (case 1, 7, 10). Metachronous lymphoma and solid tumor in 6 patients were treated with corresponding standard therapy asynchronously. Chemotherapy for colon adenocarcinoma during the interval of lymphoma chemotherapy led to excellent outcome in two patients. Immediate chemotherapy for lymphoma plus elective surgery for synchronous papillary thyroid carcinoma also yielded good prognosis in two patients with synchronous double primaries. Interestingly, we found that 10 of 11 patients with lymphoma and another solid tumor harbored germline mutations in Fanconi anemia complementation group (FANC) genes, including FANCI, FANCA, FANCG, FANCL, FANCD1, FANCF, FANCJ, and FANCS. In summary, comprehensive study of the clinical and genetic features of patients with multiple primary malignancies may improve diagnosis and treatment in the future. Mutations in FANC genes might be a predisposition to tumorigenesis of lymphoma patients with a second solid malignancy

Synaptic Neurotransmission Depression in Ventral Tegmental Dopamine Neurons and Cannabinoid-Associated Addictive Learning

Drug addiction is an association of compulsive drug use with long-term associative learning/memory. Multiple forms of learning/memory are primarily subserved by activity- or experience-dependent synaptic long-term potentiation (LTP) and long-term depression (LTD). Recent studies suggest LTP expression in locally activated glutamate synapses onto dopamine neurons (local Glu-DA synapses) of the midbrain ventral tegmental area (VTA) following a single or chronic exposure to many drugs of abuse, whereas a single exposure to cannabinoid did not significantly affect synaptic plasticity at these synapses. It is unknown whether chronic exposure of cannabis (marijuana or cannabinoids), the most commonly used illicit drug worldwide, induce LTP or LTD at these synapses. More importantly, whether such alterations in VTA synaptic plasticity causatively contribute to drug addictive behavior has not previously been addressed. Here we show in rats that chronic cannabinoid exposure activates VTA cannabinoid CB1 receptors to induce transient neurotransmission depression at VTA local Glu-DA synapses through activation of NMDA receptors and subsequent endocytosis of AMPA receptor GluR2 subunits. A GluR2-derived peptide blocks cannabinoid-induced VTA synaptic depression and conditioned place preference, i.e., learning to associate drug exposure with environmental cues. These data not only provide the first evidence, to our knowledge, that NMDA receptor-dependent synaptic depression at VTA dopamine circuitry requires GluR2 endocytosis, but also suggest an essential contribution of such synaptic depression to cannabinoid-associated addictive learning, in addition to pointing to novel pharmacological strategies for the treatment of cannabis addiction

AIDA directly connects sympathetic innervation to adaptive thermogenesis by UCP1

AIDA最早是由林圣彩教授团队首先鉴定和命名的。2007年林圣彩教授团队与孟安明院士团队合作发现AIDA在斑马鱼体轴发育中的功能(Rui, 2007)。2018年，林圣彩教授团队首次发现了AIDA在哺乳动物中的功能，即AIDA介导的内质网降解途径通过降解脂肪合成途径中的关键酶，而限制膳食脂肪在肠道的吸收这一内在抵御肥胖(Luo, 2018)。而本次成果揭示了AIDA在棕色脂肪组织中特定的功能。这些工作将AIDA引入了脂质应激代谢的重要环节，包括脂质吸收和依赖于脂质的产热过程。该论文的共同第一作者为生命科学学院博士生史猛和硕士生黄晓羽，林圣彩教授和林舒勇教授则为共同通讯作者。【Abstract】The sympathetic nervous system–catecholamine–uncoupling protein 1 (UCP1) axis plays an essential role in non-shivering adaptive thermogenesis. However, whether there exists a direct effector that physically connects catecholamine signalling to UCP1 in response to acute cold is unknown. Here we report that outer mitochondrial membrane-located AIDA is phosphorylated at S161 by the catecholamine-activated protein kinase A (PKA). Phosphorylated AIDA translocates to the intermembrane space, where it binds to and activates the uncoupling activity of UCP1 by promoting cysteine oxidation of UCP1.Adipocyte-specific depletion of AIDA abrogates UCP1-dependent thermogenesis, resulting in hypothermia during acute cold exposure. Re-expression of S161A-AIDA, unlike wild-type AIDA, fails to restore the acute cold response in Aida-knockout mice.The PKA–AIDA–UCP1 axis is highly conserved in mammals, including hibernators. Denervation of the sympathetic postganglionic fibres abolishes cold-induced AIDA-dependent thermogenesis. These findings uncover a direct mechanistic link between sympathetic input and UCP1-mediated adaptive thermogenesis.We thank Y. Li, E. Gnaiger, T. Kuwaki, J. R. B. Lighton, E. T. Chouchani and D. Jiang for technical instruction; X. Li and X.-D. Jiang (Core Facility of Biomedical, Xiamen University) for raising the p-S161-AIDA antibody; the Xiamen University Laboratory Animal Center for the mouse in vitro fertilization service and all the other members of S.C.L. laboratory for their technical assistance. This work was supported by grants from the National Key Research and Development Project of China (grant no. 2016YFA0502001) and the National Natural Science Foundation of China (grant nos 31822027, 31871168, 31690101, 91854208 and 82088102), the Fundamental Research Funds for the Central Universities (grant nos 20720190084 and 20720200069), Project ‘111’ sponsored by the State Bureau of Foreign Experts and Ministry of Education of China (grant no. BP2018017), the Youth Innovation Fund of Xiamen (grant no. 3502Z20206028), the Natural Science Foundation of Fujian Province of China (grant no. 2017J01364) and XMU Training Program of Innovation and Entrepreneurship for Undergraduates (grant no. 2019×0666). 该工作得到了厦门大学实验动物中心和生物医学学部仪器平台的重要协助和国家重点研究和发展项目，国家自然科学基金，厦门大学校长基金等的支持

Remote Sensing Image Denoising Based on Deep and Shallow Feature Fusion and Attention Mechanism

Optical remote sensing images are widely used in the fields of feature recognition, scene semantic segmentation, and others. However, the quality of remote sensing images is degraded due to the influence of various noises, which seriously affects the practical use of remote sensing images. As remote sensing images have more complex texture features than ordinary images, this will lead to the previous denoising algorithm failing to achieve the desired result. Therefore, we propose a novel remote sensing image denoising network (RSIDNet) based on a deep learning approach, which mainly consists of a multi-scale feature extraction module (MFE), multiple local skip-connected enhanced attention blocks (ECA), a global feature fusion block (GFF), and a noisy image reconstruction block (NR). The combination of these modules greatly improves the model’s use of the extracted features and increases the model’s denoising capability. Extensive experiments on synthetic Gaussian noise datasets and real noise datasets have shown that RSIDNet achieves satisfactory results. RSIDNet can improve the loss of detail information in denoised images in traditional denoising methods, retaining more of the higher-frequency components, which can have performance improvements for subsequent image processing

A Hierarchical Prediction Method for Pedestrian Head Injury in Intelligent Vehicle with Combined Active and Passive Safety System

With the development of intelligent vehicle technology, the probability of road traffic accidents occurring has been effectively reduced to a certain extent. However, there is still insufficient research on head injuries in human vehicle collisions, making it impossible to effectively predict pedestrian head injuries in accidents. To study the efficacy of a combined active and passive safety system on pedestrian head protection through the combined effect of the exterior airbag and the braking control systems of an intelligent vehicle, a “vehicle–pedestrian” interaction system is constructed in this study and is verified by real collision cases. On this basis, a combined active and passive system database is developed to analyze the cross-influence of the engine hood airbag and the vehicle braking curve parameters on pedestrian HIC (head injury criterion). Meanwhile, a hierarchy design strategy for a combined active and passive system is proposed, and a rapid prediction of HIC is achieved via the establishment of a fitting equation for each grading. The results show that the exterior airbag can effectively protect the pedestrian’s head, prevent the collision between the pedestrian’s head and the vehicle front structure, and reduce the HIC. The braking parameter H2 is significantly correlated with head injury, and when H2 is less than 1.8, the HIC value is less than 1000 in nearly 90% of cases. The hierarchy design strategy and HIC prediction method of the combined active and passive system proposed in this paper can provide a theoretical basis for rapid selection and parameter design

Conv-Former: A Novel Network Combining Convolution and Self-Attention for Image Quality Assessment

To address the challenge of no-reference image quality assessment (NR-IQA) for authentically and synthetically distorted images, we propose a novel network called the Combining Convolution and Self-Attention for Image Quality Assessment network (Conv-Former). Our model uses a multi-stage transformer architecture similar to that of ResNet-50 to represent appropriate perceptual mechanisms in image quality assessment (IQA) to build an accurate IQA model. We employ adaptive learnable position embedding to handle images with arbitrary resolution. We propose a new transformer block (TB) by taking advantage of transformers to capture long-range dependencies, and of local information perception (LIP) to model local features for enhanced representation learning. The module increases the model’s understanding of the image content. Dual path pooling (DPP) is used to keep more contextual image quality information in feature downsampling. Experimental results verify that Conv-Former not only outperforms the state-of-the-art methods on authentic image databases, but also achieves competing performances on synthetic image databases which demonstrate the strong fitting performance and generalization capability of our proposed model

Surgical Treatment of Adams Type IV Anterolateral Fracture of the Ulna Coronoid Process

Objective Anterolateral coronal fractures are so rare that the mechanism of injury, the type of combined fracture and ligament injury, and the optimal treatment are unknown. To study the outcome of surgical treatments for anterolateral (AL) fracture of the ulna coronoid process (Adams Type IV) and summarize the characteristics of this type of fracture and to guide clinical applications. Methods From February 2015 to April 2021, 32 patients were included in the study. All patients had standard radiography with anteroposterior and lateral views, computed tomography, and intraoperative fluoroscopy. All patients were treated surgically. Surgery‐related information, including surgical approach, operation duration, blood loss, and repairing the lateral collateral ligament and the medial collateral ligament integrity, were recorded. The patient's clinical details, such as the final range of motion (ROM), the Broberg–Morrey scores and the visual analogue scale (VAS) at the last follow‐up, were described. The chi‐square test or Fisher's exact test was used for statistical analysis. Results We divided patients into two groups according to the anterolateral coronoid fracture morphology. In the intact group, 20 patients with an intact anterolateral coronoid fracture fragment. In the comminuted group, 12 patients with comminuted anterolateral coronoid fracture fragments extended the less sigmoid notch of the ulna. There was no difference in age, sex, total incision length, follow‐up duration, and recovery with rehabilitation among the two groups (all Ps >0.05). The other follow‐up outcomes, such as elbow ROM (Flexion, Extension, Posterior rotation, Anterior rotation), VAS score, or Broberg–Morrey scores, were not different between the two groups (all Ps >0.05). Both groups achieved relatively satisfactory clinical outcomes, and the Broberg–Morrey score and index excellence rate reached 84.38%. There is a statistical difference in the history of elbow dislocation (P = 0.017), radial head fracture type (P = 0.041), operation duration (P = 0.014) and blood loss at operation (P = 0.029) between the two groups. Cannulated screws, anchors, and sutures were used as point fixation in the coronoid process of the ulna. There was a statistical difference between the two groups in the choice of internal fixation (P = 0.020). Conclusions For anterolateral ulnar coronoid fractures with different degrees of comminution, effective and reliable surgical treatment can achieve better results and fewer complications

Quantitative evaluation of interfacial transition zone of sustainable concrete with recycled and steel slag as aggregate

Utilizing steel slag and recycled concrete as fine aggregate could save the consumption of natural resource and reduce the environmental pollution. In this work, the effect of steel slag aggregate and recycled aggregate on the compressive strength and chloride migration coefficient of three types of concretes were investigated and compared with natural aggregate. The interfacial transition zone (ITZ) microstructure and the connection between aggregate and bulk cement matrix was determined by using a quantitative backscattered electron (BSE) image analysis, N-2 adsorption-desorption and X-ray diffraction analysis. Results showed that the compressive strength and chloride resistance ability of natural aggregate concrete (NAC) and steel slag aggregate concrete (SAC) was highly dependent on aggregate volume content. The performance of recycled aggregate concrete (RAC) were much poorer than that of SAC and NAC. Pore structure and phase analysis confirmed that the improved properties of SAC can be partially attributed to the densified ITZ. Regarding RAC, a porous ITZ was observed in BSE image and pore structure analysis, which caused a poor compressive strength and a large chloride migration coefficient. It was found that the improvement of chloride resistance ability by using supplementary cementitious materials in NAC was more remarkable than that in SAC

Discovery of Novel 2,4-Dianilinopyrimidine Derivatives Containing 4-(Morpholinomethyl)phenyl and N-Substituted Benzamides as Potential FAK Inhibitors and Anticancer Agents

Focal adhesion kinase (FAK) is responsible for the development and progression of various malignancies. With the aim to explore novel FAK inhibitors as anticancer agents, a series of 2,4-dianilinopyrimidine derivatives 8a–8i and 9a–9g containing 4-(morpholinomethyl)phenyl and N-substituted benzamides have been designed and synthesized. Among them, compound 8a displayed potent anti-FAK activity (IC50 = 0.047 ± 0.006 μM) and selective antiproliferative effects against H1975 (IC50 = 0.044 ± 0.011 μM) and A431 cells (IC50 = 0.119 ± 0.036 μM). Furthermore, compound 8a also induced apoptosis in a dose-dependent manner, arresting the cells in S/G2 phase and inhibiting the migration of H1975 cells, all of which were superior to those of TAE226. The docking analysis of compound 8a was performed to elucidate its possible binding modes with FAK. These results established 8a as our lead compound to be further investigated as a potential FAK inhibitor and anticancer agent

Fuling-Guizhi Herb Pair in Coronary Heart Disease: Integrating Network Pharmacology and In Vivo Pharmacological Evaluation

The Fuling (Poria cocos)-Guizhi (Cinnamomi ramulus) herb pair (FGHP) is a commonly used traditional Chinese herbal formula with coronary heart disease (CHD) treatment potential. However, the mechanism of FGHP in the treatment of CHD was still unclear. In this study, the action targets and underlying mechanism of FGHP against CHD were successfully achieved by combined network pharmacology prediction with experimental verification. 76 common targets were screened out by overlapping the chemical-protein data of FGHP and CHD-related targets. Then, two key targets were further selected for verification by using western blot analysis after analyzing PPI, GO function, and KEGG pathway. Results indicated FGHP could alleviate CHD syndromes and regulate inflammatory responses in acute myocardial ischemia rats, and the reduction of expression of TNF-α and IL-6 in myocardial tissue would be one of its possible underlying mechanisms. Our work demonstrated that network pharmacology combined with experimental verification provides a credible method to elucidate the pharmacological mechanism of FGHP against CHD