The mitochondrial UPR induced by ATF5 attenuates intervertebral disc degeneration via cooperating with mitophagy.

Intervertebral disc degeneration (IVDD) is an aging disease that results in a low quality of life and heavy socioeconomic burden. The mitochondrial unfolded protein response (UPRmt) take part in various aging-related diseases. Our research intents to explore the role and underlying mechanism of UPRmt in IVDD. Nucleus pulposus (NP) cells were exposed to IL-1ß and nicotinamide riboside (NR) served as UPRmt inducer to treat NP cells. Detection of ATP, NAD + and NADH were used to determine the function of mitochondria. MRI, Safranin O-fast green and Immunohistochemical examination were used to determine the degree of IVDD in vivo. In this study, we discovered that UPRmt was increased markedly in the NP cells of human IVDD tissues than in healthy controls. In vitro, UPRmt and mitophagy levels were promoted in NP cells treated with IL-1ß. Upregulation of UPRmt by NR and Atf5 overexpression inhibited NP cell apoptosis and further improved mitophagy. Silencing of Pink1 reversed the protective effects of NR and inhibited mitophagy induced by the UPRmt. In vivo, NR might attenuate the degree of IDD by activating the UPRmt in rats. In summary, the UPRmt was involved in IVDD by regulating Pink1-induced mitophagy. Mitophagy induced by the UPRmt might be a latent treated target for IVDD.

Ruptured pial-pial collateral aneurysm associated with left internal carotid artery occlusion: nuances of surgical management. Illustrative case.

BACKGROUND: Carotid occlusion often leads to the formation of a collateral network. On rare occasions, due to hemodynamic influence, aneurysms can occur. Here, the authors describe a 69-year-old male presenting with intracerebral hemorrhage secondary to a ruptured aneurysm within such a network. OBSERVATIONS: The patient presented to the emergency department with an altered level of consciousness. Imaging showed a left temporal lobe hemorrhage extending into the ventricle, subdural hematoma, and evidence of contrast extravasation. Digital subtraction angiography revealed an occluded left internal carotid artery with the left middle cerebral artery territory reconstituted by flow through an external carotid artery-internal carotid artery anastomosis. The latter was formed by the superficial temporal artery-superior orbital artery, as well as pial-pial collaterals from the posterior temporal artery. Notably, a 4-mm aneurysm arising from the pial-pial collateral network was identified. Surgical intervention involved a left temporal craniectomy and aneurysm excision, with special attention paid to preserving the anastomotic flow through the superficial temporal artery. LESSONS: This case underscores the importance of recognizing and preserving collateral vascular pathways in cases of carotid occlusion with an associated aneurysm. It emphasizes the necessary balance between managing aneurysm risk and maintaining cerebral perfusion, highlighting the need for careful preoperative planning and intraoperative caution.

Investigation of New Accelerometer Based on Capacitive Micromachined Ultrasonic Transducer (CMUT) with Ring-Perforation Membrane.

Capacitive micromachined ultrasonic transducer (CMUT) has been widely studied due to its excellent resonance characteristics and array integration. This paper presents the first study of the CMUT electrostatic stiffness resonant accelerometer. To improve the sensitivity of the CMUT accelerometer, this paper innovatively proposes the CMUT ring-perforation membrane structure, which effectively improves the acceleration sensitivity by reducing the mechanical stiffness of the elastic membrane. The acceleration sensitivity is 10.9 (Hz/g) in the acceleration range of 0-20 g, which is 100% higher than that of the conventional CMUT structure. This research contributes to the acceleration measurement field of CMUT and can effectively contribute to the breakthrough of vibration acceleration monitoring technology in aerospace, medical equipment, and automotive electronics.

Interaction between the EPHB2 receptor and EFNB1 ligand drives gastric cancer invasion and metastasis via the Wnt/ß-catenin/FAK pathway.

The survival benefit for patients with gastric cancer (GC) is modest due to its high transfer potential. Targeted therapy for metastasis-related genes in GC may be a viable approach, however, inhibitors specifically targeting GC are limited. In this study, GC patient-derived xenografts (PDX) with metastatic burden were established via orthotopic transplantation. PCR-Array analysis of primary and metastatic tumors revealed EPH receptor B2 (EPHB2) as the most significantly upregulated gene. The interaction between the EPHB2 receptor and its cognate-specific EFNB1 ligands was high in GC and correlated with a poor prognosis. Fc-EFNB1 treatment increased the invasion and migration abilities of GC cells and induced a high EPHB2 expression. EPHB2 knockdown in GC cells completely abolished the ephrin ligand-induced effects on invasion and migration abilities. Signal transduction analysis revealed Wnt/ß-catenin and FAK as downstream signaling mediators potentially inducing the EPHB2 phenotype. In conclusion, the observed deregulation of EPHB2/EFNB1 expression in GC enhances the invasive phenotype, suggesting a potential role of EPHB2/EFNB1 compound in local tumor cell invasion and the formation of metastasis.

The accuracy of multiple regression models for predicting the individual risk of recurrent lateral patellar dislocation.

BACKGROUND: Recurrent lateral patellar dislocation (RLPD) poses a significant threat to patients' quality of life due to knee pain, patellofemoral cartilage damage, and potential traumatic arthritis. Predictive scoring systems have been developed to assess the risk of RLPD; however, their relative accuracy remains uncertain. PURPOSE: To investigate the accuracy of the multiple regression models to predict the individual risk of recurrent LPD. METHODS: The Patellar Instability probability calculator (PIP), Recurrent Instability of the Patella Score (RIP), and Patellar Instability Severity Score (PIS) scoring rules were measured in 171 patients with a history of patellar dislocation and 171 healthy individuals. Three prediction models were calculated based on the data to predict the risk of recurrent lateral patellar dislocation. The inter-observer and intra-observer reliability of each measurement parameter was evaluated. The predictive capacity of the three-prediction model was investigated using the receiver operating characteristic curve. RESULTS: In the case group of 171 patients, PIS accurately predicted recurrent lateral Patella dislocation in 143 patients. RIP was 96, and PIP was 83. The positive predictive values were 92.9%, 64%, and 68% respectively. In the control group of 171 patients, the PIS was validated in 160 patients who would not experience dislocations. RIP was 117, and PIP was 50. The negative predictive values were 85.1%, 60.9%, and 36.2%, respectively. The area under the curve score for the PIS was 0.866, and the RIP was 0.673. the PIP was 0.678. CONCLUSION: RIP and PIP did not work to predict LPD. PIS can accurately predict recurrent lateral patellar dislocation. It can aid doctors in making treatment decisions. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

A single-cell atlas depicting the cellular and molecular features in human anterior cruciate ligamental degeneration: A single cell combined spatial transcriptomics study.

Background: To systematically identify cell types in the human ligament, investigate how ligamental cell identities, functions, and interactions participated in the process of ligamental degeneration, and explore the changes of ligamental microenvironment homeostasis in the disease progression. Methods: Using single-cell RNA sequencing and spatial RNA sequencing of approximately 49,356 cells, we created a comprehensive cell atlas of healthy and degenerated human anterior cruciate ligaments. We explored the variations of the cell subtypes' spatial distributions and the different processes involved in the disease progression, linked them with the ligamental degeneration process using computational analysis, and verified findings with immunohistochemical and immunofluorescent staining. Results: We identified new fibroblast subgroups that contributed to the disease, mapped out their spatial distribution in the tissue and revealed two dynamic trajectories in the process of the degenerative process. We compared the cellular interactions between different tissue states and identified important signaling pathways that may contribute to the disease. Conclusions: This cell atlas provides the molecular foundation for investigating how ligamental cell identities, biochemical functions, and interactions contributed to the ligamental degeneration process. The discoveries revealed the pathogenesis of ligamental degeneration at the single-cell and spatial level, which is characterized by extracellular matrix remodeling. Our results provide new insights into the control of ligamental degeneration and potential clues to developing novel diagnostic and therapeutic strategies. Funding: This study was funded by the National Natural Science Foundation of China (81972123, 82172508, 82372490) and 1.3.5 Project for Disciplines of Excellence of West China Hospital Sichuan University (ZYJC21030, ZY2017301).

Atomic high-spin cobalt(II) center for highly selective electrochemical CO reduction to CH3OH.

In this work, via engineering the conformation of cobalt active center in cobalt phthalocyanine molecular catalyst, the catalytic efficiency of electrochemical carbon monoxide reduction to methanol can be dramatically tuned. Based on a collection of experimental investigations and density functional theory calculations, it reveals that the electron rearrangement of the Co 3d orbitals of cobalt phthalocyanine from the low-spin state (S = 1/2) to the high-spin state (S = 3/2), induced by molecular conformation change, is responsible for the greatly enhanced CO reduction reaction performance. Operando attenuated total reflectance surface-enhanced infrared absorption spectroscopy measurements disclose accelerated hydrogenation of CORR intermediates, and kinetic isotope effect validates expedited proton-feeding rate over cobalt phthalocyanine with high-spin state. Further natural population analysis and density functional theory calculations demonstrate that the high spin Co2+ can enhance the electron backdonation via the dxz/dyz-2π* bond and weaken the C-O bonding in *CO, promoting hydrogenation of CORR intermediates.

A Systematic Review and Meta-analysis of Risk Factors for an Infection After Anterior Cruciate Ligament Reconstruction.

Background: Identifying risk factors for an infection after anterior cruciate ligament reconstruction (ACLR) and following targeted preventive strategies can effectively reduce this potentially serious complication. Purpose: To perform a systematic review and meta-analysis to identify the risk factors for an infection after ACLR. Study Design: Systematic review; Level of evidence, 4. Methods: The PubMed, Embase, and Web of Science databases were searched from inception to September 1, 2022, for prospective and retrospective studies investigating risk factors for any type of infection after ACLR. Odds ratios (ORs) or mean differences were calculated for potential risk factors if ≥2 studies assessed the same risk factor. A qualitative analysis of variables was performed if a meta-analysis could not be conducted. Results: A total of 17 studies with 141,991 patients were included in this review. The overall pooled infection rate was 0.86% (range, 0.24%-5.50%). There were 20 risk factors identified for analysis. Of these, 7 variables independently increased the odds of an infection after ACLR: (1) male sex (OR, 1.90 [95% CI, 1.33-2.73]), (2) diabetes (OR, 2.69 [95% CI, 1.66-4.35]), (3) hamstring tendon autograft (OR, 2.51 [95% CI, 2.03-3.10]), (4) revision ACLR (OR, 2.31 [95% CI, 1.22-4.37]), (5) professional athlete status (OR, 6.21 [95% CI, 1.03-37.38]), (6) lateral tenodesis (OR, 3.45 [95% CI, 1.63-7.28]), and (7) corticosteroid use (OR, 7.83 [95% CI, 3.68-16.63]). No significant associations were found between postoperative infections and age, body mass index, smoking, meniscal repair, or outpatient surgery. Conclusion: This review revealed that an increased risk of infections after ACLR was associated with male sex, diabetes, hamstring tendon autograft, revision surgery, professional athlete status, lateral tenodesis, and steroid use. Knowledge of the risk factors associated with an infection after ACLR may facilitate the identification of high-risk cases and the implementation of preventive measures to mitigate the serious consequences of this complication.

Impact of fear of recurrence in patients with cancer on caregivers' psychological health: A meta-analysis.

Objective: This study aims to quantitatively investigate the relationship between fear of cancer recurrence in patients with cancer and their caregivers' psychological health, examining the extent of the impact of this fear on caregivers. Methods: We conducted a comprehensive search in PubMed, EMBASE, Cochrane Library, Web of Science, CINAHL, and PsycINFO databases from inception until May 2023 for relevant English publications. Pearson correlation coefficients (r) were utilized as effect sizes to assess the overall relationship between fear of recurrence and psychological outcomes among caregivers of patients with cancer. Results: A total of 19 eligible studies were included in the analysis. The findings revealed a moderate positive correlation between fear of recurrence in patients with cancer and caregivers' fear of recurrence and depression. A relatively weaker correlation was observed between patients' fear of recurrence and caregivers' anxiety. Due to considerable heterogeneity (I2 â€‹= â€‹91.99%, Q â€‹= â€‹212.23), the primary outcome of fear of recurrence in patients with cancer influencing caregivers' fear of recurrence was examined through subgroup analyses. Conclusions: Our meta-analysis established a significant positive correlation between fear of recurrence in patients with cancer and negative psychological consequences among caregivers, including recurrence fear, depression, and anxiety. Future research should explore the evolution of adverse psychological outcomes in both patients with cancer and their caregivers over time and delve into the bivariate psychological impact within the patient-caregiver dyads. Systematic review registration: PROSPERO, CRD42022383866.

Crucial Factors Influencing the Involvement of Odontogenic Exosomes in Dental Pulp Regeneration.

Recent progress in exosome based studies has revealed that they possess several advantages over cells, including "cell-free" properties, low immunogenicity and ethical controversy, high biological safety and effective action. These characteristics confer exosomes significant advantages that allow them to overcome the limitations associated with traditional "cell therapy" by circumventing the issues of immune rejection, scarcity of donor cells, heterogeneity, and ethical concerns. Identification of a complete and effective radical treatment for irreversible pulpal disease, a common clinical problem, continues to pose challenges. Although traditional root canal therapy remains the primary clinical treatment, it does not fully restore the physiological functions of pulp. Although stem cell transplantation appears to be a relatively viable treatment strategy for pulp disease, issues such as cell heterogeneity and poor regeneration effects remain problematic. Dental pulp regeneration strategies based on "cell-free" exosome therapies explored by numerous studies appear to have shown significant advantages. In particular, exosomes derived from odontogenic stem cells have demonstrated considerable potential in tooth tissue regeneration engineering, and continue to exhibit superior therapeutic effects compared to non-odontogenic stem cell-derived exosomes. However, only a few studies have comprehensively summarised their research results, particularly regarding the critical factors involved in the process. Therefore, in this study, our purpose was to review the effects exerted by odontogenic exosomes on pulp regeneration and to analyse and discus crucial factors related to this process, thereby providing scholars with a feasible and manageable new concept with respect to regeneration schemes.

A deep domain adaptation framework with correlation alignment for EEG-based motor imagery classification.

It is impractical to collect sufficient and well-labeled EEG data in Brain-computer interface because of the time-consuming data acquisition and costly annotation. Conventional classification methods reusing EEG data from different subjects and time periods (across domains) significantly decrease the classification accuracy of motor imagery. In this paper, we propose a deep domain adaptation framework with correlation alignment (DDAF-CORAL) to solve the problem of distribution divergence for motor imagery classification across domains. Specifically, a two-stage framework is adopted to extract deep features for raw EEG data. The distribution divergence caused by subjected-related and time-related variations is further minimized by aligning the covariance of the source and target EEG feature distributions. Finally, the classification loss and adaptation loss are optimized simultaneously to achieve sufficient discriminative classification performance and low feature distribution divergence. Extensive experiments on three EEG datasets demonstrate that our proposed method can effectively reduce the distribution divergence between the source and target EEG data. The results show that our proposed method delivers outperformance (an average classification accuracy of 92.9% for within-session, an average kappa value of 0.761 for cross-session, and an average classification accuracy of 83.3% for cross-subject) in two-class classification tasks compared to other state-of-the-art methods.

Single-cell and spatial transcriptomics reveal changes in cell heterogeneity during progression of human tendinopathy.

BACKGROUND: Musculoskeletal tissue degeneration impairs the life quality and motor function of many people, especially seniors and athletes. Tendinopathy is one of the most common diseases associated with musculoskeletal tissue degeneration, representing a major global healthcare burden that affects both athletes and the general population, with the clinical presentation of long-term recurring chronic pain and decreased tolerance to activity. The cellular and molecular mechanisms at the basis of the disease process remain elusive. Here, we use a single-cell and spatial RNA sequencing approach to provide a further understanding of cellular heterogeneity and molecular mechanisms underlying tendinopathy progression. RESULTS: To explore the changes in tendon homeostasis during the tendinopathy process, we built a cell atlas of healthy and diseased human tendons using single-cell RNA sequencing of approximately 35,000 cells and explored the variations of cell subtypes' spatial distributions using spatial RNA sequencing. We identified and localized different tenocyte subpopulations in normal and lesioned tendons, found different differentiation trajectories of tendon stem/progenitor cells in normal/diseased tendons, and revealed the spatial location relationship between stromal cells and diseased tenocytes. We deciphered the progression of tendinopathy at a single-cell level, which is characterized by inflammatory infiltration, followed by chondrogenesis and finally endochondral ossification. We found diseased tissue-specific endothelial cell subsets and macrophages as potential therapeutic targets. CONCLUSIONS: This cell atlas provides the molecular foundation for investigating how tendon cell identities, biochemical functions, and interactions contributed to the tendinopathy process. The discoveries revealed the pathogenesis of tendinopathy at single-cell and spatial levels, which is characterized by inflammatory infiltration, followed by chondrogenesis, and finally endochondral ossification. Our results provide new insights into the control of tendinopathy and potential clues to developing novel diagnostic and therapeutic strategies.

Anatomical factors associated with the development of anterior tibial spine fractures based on MRI measurements.

BACKGROUND: Numerous studies have investigated anatomic factors for anterior cruciate ligament (ACL) injuries, such as posterior tibial slope (PTS) and notch width index (NWI). However, anterior tibial spine fracture (ATSF) as a specific pattern of ACL injury, a bony avulsion of the ACL from its insertion on the intercondylar spine of the tibia, has rarely been explored for its anatomical risk factors. Identifying anatomic parameters of the knee associated with ATSF is important for understanding injury mechanisms and prevention. METHODS: Patients who underwent surgery for ATSF between January 2010 and December 2021 were retrospectively reviewed, and 38 patients were included in the study group. Thirty-eight patients who suffered from isolated meniscal tear without other pathologic findings were matched in a 1:1 fashion by age, sex and BMI to the study group. The lateral posterior tibial slope (LPTS), medial posterior tibial slope (MPTS), medial tibial depth, lateral tibial height, lateral femoral condyle ratio (LFCR) and NWI were measured and compared between the ATSF and control groups. Binary logistic regressions identified independent predictors of ATSF. Receiver operator characteristic (ROC) curves were performed to compare the diagnostic performance and determine the cutoff values of associated parameters. RESULTS: The LPTS, LFCR and MPTS were significantly larger in the knees in the ATSF group than in the control group (P = 0.001, P = 0.012 and P = 0.005, respectively). The NWI was significantly smaller in the knees in the ATSF group than in the control group (P = 0.005). According to the results of logistic regression analysis, the LPTS, LFCR and NWI were independently associated with ATSF. The LPTS was the strongest predictor variable, and the ROC analysis revealed 63.2% sensitivity and 76.3% specificity (area under the curve, 0.731; 95% CI 0.619-0.844) for values above 6.9. CONCLUSION: The LPTS, LFCR and NWI were found to be associated with the ATSF; in particular, LPTS could provide the most accurate predictive performance. The findings of this study may aid clinicians in identifying people at risk for ATSF and taking individualized preventive measures. However, further investigation regarding the pattern and biomechanical mechanisms of this injury is required.

Characteristics of shunt failure in 38,095 adult shunt insertion surgeries: a systematic review and meta-analysis.

OBJECTIVE: The management of excess CSF in patients with hydrocephalus typically requires using a shunt to divert CSF. Unfortunately, there is a high rate of shunt failure despite improvements in device components and insertion techniques. Reoperation is frequently necessary, which contributes to patient harm and increased healthcare costs. While factors affecting shunt failure are well defined in the pediatric population, information regarding adults is lacking. The authors undertook a systematic review and meta-analysis to determine how shunt failure in the adult population is reported and investigated the etiologies of shunt failure. METHODS: This review is reported according to PRIMSA and utilized the MEDLINE, Embase, and Google Scholar databases. Abstracts were screened by two independent reviewers, and data were extracted in duplicate by two independent reviewers. Statistical analyses were performed using SPSS and Stata. RESULTS: The pooled rates of shunt failure were 10% (95% CI 5%-15%) in studies with a mean follow-up time of less than 1 year, 12% (95% CI 8%-14%) with a follow-up time between 1 and 2 years, and 32% in studies with a follow-up time of 2 years or greater (95% CI 19%-43%). The pooled rate of failure was 17% across all studies. The most common cause of shunt failure was obstruction at 3.0% (95% CI 2%-4%), accounting for 23.2% of shunt failures. Infection was the second most common at 2.8% (95% CI 2%-3%), accounting for 22.5% of shunt failures. The most common location of shunt failure was the distal catheter, with a failure rate of 4.0% (95% CI 3%-5%), accounting for 33.4% of shunt failures. The definition of shunt failure was heterogeneous and varied depending on institutional practices. The combination of symptoms with either CT or MRI was the most frequently reported method for assessing shunt failure. CONCLUSIONS: Important variation regarding how to define, investigate, and report shunt failure was identified. The overall shunt failure rate in adults is at least 32% after 2 years, which, while lower than that typically reported in the pediatric population, is significant. The most common causes of shunt failure in adults are infection and obstruction. The most common site of failure occurred at the distal catheter, highlighting the need to develop strategies to both report and mitigate distal shunt failure in adult shunt patients.

Sesn2 Serves as a Regulator between Mitochondrial Unfolded Protein Response and Mitophagy in Intervertebral Disc Degeneration.

Mitochondrial unfold protein response (UPRmt) can induce mitophagy to protect cell from unfold protein. However, how UPRmt induces mitophagy to protect cell is not yet clear. Herein, Sesn2 was considered to be a key molecule that communicated UPRmt and mitophagy in the intervertebral disc. Silencing of Sesn2 was able to reverse the protective effects of Nicotinamide riboside (NR) on nucleus pulposus (NP) cells and inhibit mitophagy induced by UPRmt. UPRmt upregulated Sesn2 through Eif2ak4/eIF2α/Atf4, and further induced mitophagy. Sesn2 promoted the translocation of cytosolic Parkin and Sqstm1 to the defective mitochondria respectively, thereby enhancing mitophagy. The translocation of cytosolic Sqstm1 to the defective mitochondria was dependent on Parkin. The two functional domains of Sesn2 were necessary for the interaction of Sesn2 with Parkin and Sqstm1. The cytosolic interaction of Sesn2 between Parkin and Sqstm1 was independent on Pink1 (named as PINK1 in human) but the mitochondrial translocation was dependent on Pink1. Sesn2-/- mice showed a more severe degeneration and NR did not completely alleviate the intervertebral disc degeneration (IVDD) of Sesn2-/- mice. In conclusion, UPRmt could attenuate IVDD by upregulation of Sesn2-induced mitophagy. This study will help to further reveal the mechanism of Sesn2 regulating mitophagy, and open up new ideas for the prevention and treatment of IVDD.

Ultrasound Elastography in Neurosurgery: Current Applications and Future Perspectives.

BACKGROUND: Similar to clinical palpation, Ultrasound elastography (USE) helps distinguish between tissues by providing information on their elasticity. While it has been widely explored and has been applied to many body organs, USE has not been studied as extensively for application in neurosurgery. The current systematic review was performed to identify articles related to the use of interoperative USE in neurosurgery. METHODS: Search included MEDLINE(R) database. Only original peer-reviewed full-text articles were included. No language or publication year restrictions were imposed. Two independent reviewers assessed the search results for relevance. The identified articles were screened by title, abstract, and full-text review. RESULTS: Seventeen articles were included in the qualitative analysis and 13 articles were related to oncology, epilepsy (n = 3), and spine (n = 1). In oncology, USE was found useful in defining tumor stiffness, aiding surgical planning, detecting residual tumors, discriminating between tumor and brain tissue, and differentiating between different tumors. In epilepsy, USE could improve the detection of epileptogenic foci, thereby enhancing the prospect of complete and safe resection. The application in spinal surgery was limited to demonstrating that a compressed spinal cord is stiffer than the decompressed one. CONCLUSIONS: USE was found to be a safe, quick, portable, and economic tool that was a useful intraoperative adjunct to provide information corresponding to a variety of neurosurgical diseases, at different stages of surgery. This review describes the current intraoperative neurosurgical applications of USE, the concept of elasticity, and different USE modalities as well as the technical challenges, limitations, and possible future implications.

Detecting monocyte trafficking in an animal model of glioblastoma using R2* and quantitative susceptibility mapping.

BACKGROUND: The role of tumor-associated macrophages (TAMs) in glioblastoma (GBM) disease progression has received increasing attention. Recent advances have shown that TAMs can be re-programmed to exert a pro-inflammatory, anti-tumor effect to control GBMs. However, imaging methods capable of differentiating tumor progression from immunotherapy treatment effects have been lacking, making timely assessment of treatment response difficult. We showed that tracking monocytes using iron oxide nanoparticle (USPIO) with MRI can be a sensitive imaging method to detect therapy response directed at the innate immune system. METHODS: We implanted syngeneic mouse glioma stem cells into C57/BL6 mice and treated the animals with either niacin (a stimulator of innate immunity) or vehicle. Animals were imaged using an anatomical MRI sequence, R2* mapping, and quantitative susceptibility mapping (QSM) before and after USPIO injection. RESULTS: Compared to vehicles, niacin-treated animals showed significantly higher susceptibility and R2*, representing USPIO and monocyte infiltration into the tumor. We observed a significant reduction in tumor size in the niacin-treated group 7 days later. We validated our MRI results with flow cytometry and immunofluoresence, which showed that niacin decreased pro-inflammatory Ly6C high monocytes in the blood but increased CD16/32 pro-inflammatory macrophages within the tumor, consistent with migration of these pro-inflammatory innate immune cells from the blood to the tumor. CONCLUSION: MRI with USPIO injection can detect therapeutic responses of innate immune stimulating agents before changes in tumor size have occurred, providing a potential complementary imaging technique to monitor cancer immunotherapies. MANUSCRIPT HIGHLIGHT: We show that iron oxide nanoparticles (USPIOs) can be used to label innate immune cells and detect the trafficking of pro-inflammatory monocytes into the glioblastoma. This preceded changes in tumor size, making it a more sensitive imaging technique.

Cellular features of localized microenvironments in human meniscal degeneration: a single-cell transcriptomic study.

Background: Musculoskeletal tissue degeneration impairs the life quality and function of many people. Meniscus degeneration is a major origin of knee osteoarthritis and a common threat to athletic ability, but its cellular mechanism remains elusive. Methods: We built a cell atlas of 12 healthy or degenerated human meniscus samples from the inner and outer meniscal zones of 8 patients using scRNA-seq to investigate meniscal microenvironment homeostasis and its changes in the degeneration process and verified findings with immunofluorescent imaging. Results: We identified and localized cell types in inner and outer meniscus and found new chondrocyte subtypes associated with degeneration. The observations suggested understandings on how cellular compositions, functions, and interactions participated in degeneration, and on the possible loop-like interactions among extracellular matrix disassembly, angiogenesis, and inflammation in driving the degeneration. Conclusions: The study provided a rich resource reflecting variations in the meniscal microenvironment during degeneration and suggested new cell subtypes as potential therapeutic targets. The hypothesized mechanism could also be a general model for other joint degenerations. Funding: The National Natural Science Foundation of China (81972123, 82172508, 62050178, 61721003), the National Key Research and Development Program of China (2021YFF1200901), Fundamental Research Funds for the Central Universities (2015SCU04A40); The Innovative Spark Project of Sichuan University (2018SCUH0034); Sichuan Science and Technology Program (2020YFH0075); Chengdu Science and Technology Bureau Project (2019-YF05-00090-SN); 1.3.5 Project for Disciplines of Excellence of West China Hospital Sichuan University (ZYJC21030, ZY2017301); 1.3.5 Project for Disciplines of Excellence - Clinical Research Incubation Project, West China Hospital, Sichuan University (2019HXFH039).

Long-range high-speed laser imaging based on VCSEL array and MPPC array.

Flash LiDAR is a photoelectric system that can acquire a 3D image by emitting a diffuse pulsed laser beam, and hence is suitable for both autopilot and spacecraft flight control. Achieving long-range and high-speed, especially in outdoor applications with strong solar background illumination, are challenging requirements. In this paper, a set of laser imaging prototype based on 2×6 VCSEL array and 32×32 MPPC array image sensor is developed, the range calibration is completed, and relevant experimental research is carried out. The frame rate of the system can reach 10kHz, the detection probability of 120m range can reach 86.23%, and the maximum walk error is about 0.6m under different reflectivity. The 3D imaging of the vehicle can be realized at about 70m, the horizontal spatial resolution is less than 5cm, and the ranging precision after ten shots average is within 10cm by calculating the centroid of a histogram. The detection probability can be improved by using the time-gating method. After multiple measurements, a 120m "laser imaging through window" can be realized in sunlight. This LiDAR system has the advantages of small volume, light weight and fast detection speed.

Environmental Pollution Liability Insurance and Corporate Performance: Evidence from China in the Perspective of Green Development.

Environmental pollution is an inevitable primary responsibility in the production and management of enterprises, and it is the most severe challenge to achieving green production and sustainable development. Environmental pollution liability insurance (EPLI) can transfer corporate pollution liability to insurance companies, which affects corporate performance to a certain extent. However, the influencing factors of enterprise performance are complex, and EPLI also involves multiple subjects, so the impact of EPLI on enterprise performance is also complex. At first, this paper analyzes the possible relationship between EPLI and corporate performance based on the existing literature; subsequently, based on the list of EPLI-insured companies in 2014 and 2015 published by China's environmental protection department as a sample, this paper uses a fixed-effects model to conduct an empirical analysis, and the mediating role of corporate social responsibility (CSR) was then examined; finally, heterogeneity analysis of the initial conclusions was conducted. The following conclusions are drawn: firstly, there is a significant negative correlation between EPLI and corporate performance. Secondly, CSR played a mediating role in the effect of EPLI on corporate performance; that is, EPLI inhibited the rise of corporate performance by affecting CSR. Thirdly, the impact of EPLI on corporate performance is heterogeneous in terms of equity nature, corporate pollution level and marketization degree. The results of this paper enrich the economic impact theory of EPLI and have specific practical value for enterprise management and policymakers in the background of the green economy.