Mitochondria in innate immunity signaling and its therapeutic implications in autoimmune diseases

Autoimmune diseases are characterized by vast alterations in immune responses, but the pathogenesis remains sophisticated and yet to be fully elucidated. Multiple mechanisms regulating cell differentiation, maturation, and death are critical, among which mitochondria-related cellular organelle functions have recently gained accumulating attention. Mitochondria, as a highly preserved organelle in eukaryotes, have crucial roles in the cellular response to both exogenous and endogenous stress beyond their fundamental functions in chemical energy conversion. In this review, we aim to summarize recent findings on the function of mitochondria in the innate immune response and its aberrancy in autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, etc., mainly focusing on its direct impact on cellular metabolism and its machinery on regulating immune response signaling pathways. More importantly, we summarize the status quo of potential therapeutic targets found in the mitochondrial regulation in the setting of autoimmune diseases and wish to shed light on future studies

Bridging the Granularity Gap for Acoustic Modeling

While Transformer has become the de-facto standard for speech, modeling upon the fine-grained frame-level features remains an open challenge of capturing long-distance dependencies and distributing the attention weights. We propose \textit{Progressive Down-Sampling} (PDS) which gradually compresses the acoustic features into coarser-grained units containing more complete semantic information, like text-level representation. In addition, we develop a representation fusion method to alleviate information loss that occurs inevitably during high compression. In this way, we compress the acoustic features into 1/32 of the initial length while achieving better or comparable performances on the speech recognition task. And as a bonus, it yields inference speedups ranging from 1.20$\times$ to 1.47$\times$. By reducing the modeling burden, we also achieve competitive results when training on the more challenging speech translation task.Comment: ACL 2023 Finding

Increasing Area and Decreasing Depth: Climate Change Influence on Snow Variations in the Qilian Mountains

The Qilian Mountains serve as a critical water source for the Yellow River and various inland rivers, playing a pivotal role in regulating the regional climate. Given their significance as one of the foremost water resources in the area, the spatial and temporal dynamics of the snow are crucial for understanding potential impacts on regional hydrology and ecology. This study examines the characteristics of spatial and temporal variations in snow-covered extent (SCE), snow depth (SD), snow-covered days (SCD), snow onset date (SOD), and snow end date (SED) within the Qilian Mountains region. We investigate the hydrological and ecological implications utilizing snow area and phenology data, alongside SD data. The findings indicate that: (1) the distribution of snow across the Qilian Mountains mainly splits between the central and western areas, with the central region showing deeper snow than both the eastern and western parts; (2) the area covered by snow in the Qilian Mountains is growing, but the depth of the snow is on a decline, especially in the central area; (3) in terms of snow phenology, most of the region is witnessing an earlier start of SOD, a longer SCD, and an earlier SED. An overall increase in precipitation is identified as the key factor behind the expanded SCE in the Qilian Mountains, while rising temperatures are pinpointed as the primary cause for the reduction in SD. As global climate change intensifies, the observed alterations in the snow of the Qilian Mountains present emerging challenges for regional water security and ecological equilibrium

Innate Lymphoid Cell Biology: Lessons Learnt from Natural Killer Cells

Group 1 innate lymphoid cells (ILC) comprise the natural killer (NK) cells and ILC1 which reside within peripheral tissues. Several different ILC1 subsets have recently been characterised, however no unique markers to define these subsets have been identified. Whether ILC1 and NK cells are in fact distinct lineages, or alternately exhibit transitional molecular programs, that allow them to adapt to different tissue niches remains an open question. NK cells are the prototypic member of the Group 1 ILC and have been historically assigned the functions of what now appears to be a multi-subset family that are distributed throughout the body. This raises the question of whether each of these populations mediate distinct functions during infection and tumour immunosurveillance. Here, we review the diversity in the Group 1 ILC subsets with regards to their transcriptional regulation, localization, mobility and receptor expression and highlight the challenges in unraveling the individual functions of these different populations of cells

The Roles of Innate Lymphoid Cells in the Gastric Mucosal Immunology and Oncogenesis of Gastric Cancer

Innate lymphoid cells (ILCs) are a group of innate immune cells that have garnered considerable attention due to their critical roles in regulating immunity and tissue homeostasis. They are particularly abundant in the gastrointestinal tract, where they have been shown to interact with commensal bacteria, pathogens, and other components of the local microenvironment to influence host immune responses to infection and oncogenesis. Their tissue-residency properties enable gastric ILCs a localized and rapid response to alert and stress, which indicates their key potential in regulating immunosurveillance. In this review, we discuss the current understanding of the role of ILCs in the gastric mucosa, with a focus on their interactions with the gastric microbiota and Helicobacter pylori and their contributions to tissue homeostasis and inflammation. We also highlight recent findings on the involvement of ILCs in the pathogenesis of gastric cancer and the implications of targeting ILCs as a therapeutic approach. Overall, this review provides an overview of the diverse functions of ILCs in gastric mucosa and highlights their potential as targets for future therapies for gastric cancer

From the Destruction of Two Lumbar Segments to Thoracic‐Lumbar‐Pelvic Fusion: A Case Caused by Congenital Insensitivity to Pain with Anhidrosis and Literature Review

Background Congenital insensitivity to pain with anhidrosis (CIPA) with Charcot arthropathy is a rare combination in orthopaedic clinical practice. The experience dealing with such patients is limited. Here with this case of approximately 10 years follow‐up, we wish to shed light on the choices of strategies of surgeries and alerting clinicians with post‐surgery complications. The possible underlying reasons for the recurrent Charcot arthropathies as well as strategies for peri‐operative management for such surgical cases are also discussed. Case Presentation The patient underwent a surgery to correct her severe kyphosis caused by CIPA‐related Charcot spine. Multiple post‐surgery complications occurred during her follow‐up, including hardware migration, adjacent segment disease (ASD), and loosening pedicle screws. Five revision surgeries were conducted consequently. From the limited experience on the management of CIPA‐related Charcot spine, surgical correction is still the first‐line treatment. Conclusions Of all the 16 cases reviewed (including our case), loosening pedicle screws, hardware migration, and ASDs are the common post‐surgery complications. Large‐scale removal of damaged vertebrae and subsequent reconstruction are not recommended, which might increase the risk of hardware migration. A 360° long‐segment fusion might be of help to reduce the risk of ASDs. In the meantime, comprehensive management including careful nursing, proper rehabilitation exercises, and treatments targeting bone mineral metabolism is also critical

A Case Report of Congenital Insensitivity to Pain with Anhidrosis

Congenital insensitivity to pain with anhidrosis (CIPA) is associated with Charcot arthropathy and is a rare clinical syndrome, with limited treatment options. Through a decade-long follow-up of a single case, we aim to provide new insights for clinicians regarding the choice of surgical strategies and postoperative complications. The diagnosed patient exhibited congenital insensitivity to pain and anhidrosis, accompanied by severe Charcot arthropathy affecting the spine. Multiple postoperative complications, including implant displacement, adjacent segment pathology, and pedicle screw loosening, occurred after surgical intervention, leading to five subsequent revision surgeries. Considering the limited experience in managing CIPA-related Charcot spinal arthropathy in the literature, surgical correction remains the preferred treatment. Among the 16 cases reviewed, common postoperative complications included implant displacement, adjacent segment pathology, and pedicle screw loosening. Based on current experience, we do not recommend extensive resection and reconstruction after removing the affected vertebral body, as this may increase the risk of implant displacement. Instead, a 360° long-segment fusion may help reduce the risk of adjacent segment degeneration. Additionally, we discuss potential reasons for revision surgery after Charcot spinal arthropathy surgery and perioperative management strategies for such cases. Meticulous care, appropriate rehabilitation exercises, and metabolic therapy for bone mineralization are crucial components of the treatment for this condition

Rock Climbing-Inspired Electrohydrodynamic Cryoprinting of Micropatterned Porous Fiber Scaffolds with Improved MSC Therapy for Wound Healing

Abstract Impaired wound healing imposes great health risks to patients. Recently, mesenchymal stem cell (MSC) therapy has shown potential to improve the healing process, but approaches to employ MSCs in the treatment of wounds remain elusive. In this study, we reported a novel electrohydrodynamic (EHD) cyroprinting method to fabricate micropatterned fiber scaffolds with polycaprolactone (PCL) dissolved in glacial acetic acid (GAC). Cyroprinting ensured the formation of a porous structure of PCL fibers by preventing the evaporation of GAC, thus increasing the surface roughness parameter Ra from 11 to 130 nm. Similar to how rough rocks facilitate easy climbing, the rough surface of fibers was able to increase the adhesion of adipose-derived MSCs (AMSCs) by providing more binding sites; therefore, the cell paracrine action of secreting growth factors and chemokines was enhanced, promoting fibroblast migration and vascular endothelial cell tube formation. In rat models with one-centimeter wound defects, enhanced MSC therapy based on porous PCL fiber scaffolds improved wound healing by augmenting scarless collagen deposition and angiogenesis and reducing proinflammatory reactions. Altogether, this study offers a new and feasible strategy to modulate the surface topography of polymeric scaffolds to strengthen MSC therapy for wound healing. Graphic Abstrac

A Pineapple Target Detection Method in a Field Environment Based on Improved YOLOv7

The accurate detection of pineapples of different maturity levels in a complex field environment is the key step to achieving the early yield estimation and mechanized picking of pineapple. This study proposes a target detection model based on the improved YOLOv7 to achieve the accurate detection and maturity classification of pineapples in the field. First, the attention mechanism SimAM is inserted into the structure of the original YOLOv7 network to improve the feature extraction ability of the model. Then, the max-pooling convolution (MPConv) structure is improved to reduce the feature loss in the downsampling process. Finally, the non-maximum suppression (NMS) algorithm is replaced by the soft-NMS algorithm, with a better effect at improving the detection effect when pineapple is in occlusion or overlaps. According to the test, the mean average precision (mAP) and recall of the model proposed in this paper are 95.82% and 89.83%, which are 2.71% and 3.41% higher than those of the original YOLOv7, respectively. The maturity classification accuracy of the model and the detection performance under six different field scenarios were analyzed quantitatively. This method provides an effective scheme for the vision system of the field pineapple picking robot

Single-Cell Profiling of the Immune Atlas of Tumor-Infiltrating Lymphocytes in Endometrial Carcinoma

Endometrial carcinoma (EC) is a gynecological malignancy with a high incidence; however, thorough studies on tumor-infiltrating lymphocyte (TIL) populations in EC are lacking. We aimed to map the immune atlas of TILs in type I EC via single-cell RNA sequencing (scRNA-seq), mass cytometry and flow cytometry analysis. We found that natural killer (NK) cells and CD8+ T lymphocytes were the major components of TILs in EC patients. We first identified three transcriptionally distinct NK cell subsets, which are likely to possess diverse anti-tumor functions. Additionally, CD103+ cells substantially contributed to the CD8+ T cell population. The signature gene expression of CD103+ CD8+ T cells indicated the tissue residency, immunological memory, and exhaustion properties of this cell subset, which were defined as tissue-resident memory T cells (TRM cells). Moreover, based on scRNA-seq and mass cytometry analysis, we first identified the intrinsic heterogeneity of CD103+ CD8+ T cells that were thought to have a distinct cytotoxicity, cell adhesion and exhaustion status functions. Collectively, distinct subsets of NK cells were found and might shed light on future investigations. CD103+ CD8+ T cell population may be an important immunotherapeutic target in EC and targeting this cell population with combined immunosuppressive therapy might improve the efficacy of immunotherapy for EC