Efficacy and safety of thalidomide for recurrent aphthous stomatitis: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is considered as the most common oral mucosal lesion affecting up to 25% of people worldwide. Thalidomide has been reported for the treatment of RAS, but the evidence has not been systematically evaluated. We first systematically reviewed the efficacy and safety of thalidomide for the treatment of RAS. METHODS: We searched The Cochrane Library, PubMed, Scopus, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature Database (CBM), Wanfang Data, and VIP information from inception to December 2023. Randomized controlled trials (RCTs) comparing thalidomide with control for RAS were included in the analysis. The primary outcome were complete response and overall response, and the secondary outcome were recurrence interval (RI), ulcer number and size, healing time, visual analogue scale (VAS), immunological data, and adverse events. Meta-analysis was conducted using the Review Manager 5.4 software. RESULTS: Twenty-one trials involving 1668 patients were included in this review. The results of our meta-analysis showed that thalidomide significantly improved the complete response rate and overall response rate, prolonged the recurrence interval, accelerated the healing process, reduced the number and size of ulcers, and lowered TNF-α levels in the treatment of RAS. However, thalidomide significantly increases adverse events. RESULTS: Thalidomide has a significant benefit in the treatment of RAS. However, considering the potential side effects of thalidomide, it may be an optimal treatment option for major RAS patients or cases that do not respond to topical agents. TRIAL REGISTRATION: PROSPERO registration number: CRD42024495038.

Lymphangiogenesis: novel strategies to promote cutaneous wound healing.

The cutaneous lymphatic system regulates tissue inflammation, fluid balance and immunological responses. Lymphangiogenesis or lymphatic dysfunction may lead to lymphedema, immune deficiency, chronic inflammation etc. Tissue regeneration and healing depend on angiogenesis and lymphangiogenesis during wound healing. Tissue oedema and chronic inflammation can slow wound healing due to impaired lymphangiogenesis or lymphatic dysfunction. For example, impaired lymphangiogenesis or lymphatic dysfunction has been detected in nonhealing wounds such as diabetic ulcers, venous ulcers and bedsores. This review summarizes the structure and function of the cutaneous lymphatic vessel system and lymphangiogenesis in wounds. Furthermore, we review wound lymphangiogenesis processes and remodelling, especially the influence of the inflammatory phase. Finally, we outline how to control lymphangiogenesis to promote wound healing, assess the possibility of targeting lymphangiogenesis as a novel treatment strategy for chronic wounds and provide an analysis of the possible problems that need to be addressed.

Exploring the constitutive activation mechanism of the class A orphan GPR20.

GPR20, an orphan G protein-coupled receptor (GPCR), shows significant expression in intestinal tissue and represents a potential therapeutic target to treat gastrointestinal stromal tumors. GPR20 performs high constitutive activity when coupling with Gi. Despite the pharmacological importance of GPCR constitutive activation, determining the mechanism has long remained unclear. In this study, we explored the constitutive activation mechanism of GPR20 through large-scale unbiased molecular dynamics simulations. Our results unveil the allosteric nature of constitutively activated GPCR signal transduction involving extracellular and intracellular domains. Moreover, the constitutively active state of the GPR20 requires both the N-terminal cap and Gi protein. The N-terminal cap of GPR20 functions like an agonist and mediates long-range activated conformational shift. Together with the previous study, this study enhances our knowledge of the self-activation mechanism of the orphan receptor, facilitates the drug discovery efforts that target GPR20.

Single-cell RNA sequencing illuminates the ontogeny, conservation and diversification of cartilaginous and bony fish lymphocytes.

Elucidating cellular architecture and cell-type evolution across species is central to understanding immune system function and susceptibility to disease. Adaptive immunity is a shared trait of the common ancestor of cartilaginous and bony fishes. However, evolutionary features of lymphocytes in these two jawed vertebrates remain unclear. Here, we present a single-cell RNA sequencing atlas of immune cells from cartilaginous (white-spotted bamboo shark) and bony (zebrafish and Chinese tongue sole) fishes. Cross-species comparisons show that the same cell types across different species exhibit similar transcriptional profiles. In the bamboo shark, we identify a phagocytic B cell population expressing several pattern recognition receptors, as well as a T cell sub-cluster co-expressing both T and B cell markers. In contrast to a division by function in the bony fishes, we show close linkage and poor functional specialization among lymphocytes in the cartilaginous fish. Our cross-species single-cell comparison presents a resource for uncovering the origin and evolution of the gnathostome immune system.

Discovery of an unconventional lamprey lymphocyte lineage highlights divergent features in vertebrate adaptive immune system evolution.

Lymphocyte receptors independently evolved in both jawed and jawless vertebrates with similar adaptive immune responses. However, the diversity of functional subtypes and molecular architecture in jawless vertebrate lymphocytes, comparable to jawed species, is not well defined. Here, we profile the gills, intestines, and blood of the lamprey, Lampetra morii, with single-cell RNA sequencing, using a full-length transcriptome as a reference. Our findings reveal higher tissue-specific heterogeneity among T-like cells in contrast to B-like cells. Notably, we identify a unique T-like cell subtype expressing a homolog of the nonlymphoid hematopoietic growth factor receptor, MPL-like (MPL-L). These MPL-L+ T-like cells exhibit features distinct from T cells of jawed vertebrates, particularly in their elevated expression of hematopoietic genes. We further discovered that MPL-L+ VLRA+ T-like cells are widely present in the typhlosole, gill, liver, kidney, and skin of lamprey and they proliferate in response to both a T cell mitogen and recombinant human thrombopoietin. These findings provide new insights into the adaptive immune response in jawless vertebrates, shedding new light on the evolution of adaptive immunity.

Effects of Thermal Exposure Temperature on Room-Temperature Tensile Properties of Ti65 Alloy.

As a critical material for high-temperature components of aero-engines, the mechanical properties of Ti65 alloy, subjected to high-temperature and long-term thermal exposure, directly affect its service safety. The room-temperature tensile properties of the Ti65 alloy after thermal exposure to temperatures ranging from 450 °C to 650 °C for 100 h were investigated. The results indicate that as the thermal exposure temperature increases, the strength of Ti65 alloy initially increases and then decreases, while ductility exhibits a decreasing trend. The strength of the thermally exposed alloy positively correlates with the size and content of the α2 phase. The ductility of the thermally exposed alloy is comprehensively influenced by the surface oxidation behavior, α2 phase, and silicides. After the prolonged thermal exposure, stress concentration at the crack tips within the oxide layer was enhanced with the increased thickness of the surface TiO2 oxide layer, leading to premature fracture due to reduced alloy ductility. Furthermore, the α2 phase in the matrix promotes the planar slip of dislocations, while silicides at the α/ß phase boundaries hinder dislocation motion, causing dislocation pile-ups. Both behaviors facilitate crack nucleation and deteriorate alloy ductility.

[Free vastus lateralis flap combined with skin grafting for repairing small- and medium-sized lacunar defects in non-weight-bearing area of diabetic foot].

Objective: To explore the feasibility and effectiveness of free vastus lateralis flap combined with skin grafting for repairing small- and medium-sized lacunar defects in the non-weight-bearing area of diabetic foot. Methods: Between January 2022 and October 2023, 8 patients (8 feet) with small- and medium-sized lacunar defects in the non-weight-bearing area of diabetic foot were admitted. There were 6 males and 2 females, with an average age of 64.3 years (range, 58-76 years). The duration of the diabetic foot ulcer ranged from 2 to 7 weeks (mean, 4.3 weeks). The wound was located between the metatarsal bones in 4 cases, on the medial side of the foot in 2 cases, on the lateral side of the foot in 1 case, and on the dorsal and lateral sides of the foot in 1 case. The length of wound was 4.0-12.0 cm, the width was 3.0-5.0 cm, and the depth was 1.2-2.0 cm. The free vastus lateralis flaps were designed to repair the wounds, and skin grafting covered the vastus lateralis flaps. The length of the vastus lateralis flap was 5.0-14.0 cm, the width was 3.5-6.0 cm, and the thickness was 1.0-1.5 cm. The donor sites of the muscle flaps were directly sutured. Results: The time for vastus lateralis flaps harvested ranged from 30 to 80 minutes (mean, 55.0 minutes), and the total operation time ranged from 125 to 170 minutes (mean, 147.5 minutes). All muscle flaps and skin grafts survived successfully, and the wounds and the incisions at the donor sites healed by first intention. All patients were followed up 6-24 months, with an average of 12.8 months. The appearances of 3 patients who did not follow the doctor's instructions for pressure treatment of the muscle flaps were a little bloated, and the rest had a good appearance. The texture of the muscle flaps was soft. There were linear scars at the donor sites. There was no recurrence of ulcers during follow-up. All patients could walk independently without limitation of daily activities at last follow-up. Conclusion: The application of free vastus lateralis flap combined with skin grafting to repair small- and medium-sized lacunar defects in the non-weight-bearing area of diabetic foot has the advantages of simple operation and time-saving as well as small damage to the donor site, with good repair effect, especially for the elderly patients who are not suitable for prolonged anesthesia.

[Application of intra-articular graft length measurement in total anterior cruciate ligament reconstruction].

OBJECTIVE: To investigate the clinical efficacy of arthroscopic measurement of intra-articular graft length in the application of total internal reconstruction of the anterior cruciate ligament(ACL). METHODS: The 60 patients with ACL injury treated between January 2020 and January 2022 were retrospectively analyzed. There were 37 males and 23 females, aged from 22 to 44 years. According to the different surgical methods, they were divided into two groups:conventional surgery group (conventional group) and pull-line measurement group (measurement group), with 30 cases in each group. In the conventional group, there were 20 males and 10 females, with an average age of (30.00±3.95) years old;the body mass index (BMI) was (22.58±1.41) kg·m-2;there were 9 cases on the left side and 21 cases on the right side;the time from injury to operation was (3. 00±1.35) days. In the measurement group, there were 17 males and 13 females, with an average of(32.00±4.29) years;BMI was (23.29±1.39) kg·m-2;there were 12 cases on the left side and 18 cases on the right side;the time from injury to operation was (3.00±1.27) days. The clinical data of the patients before surgery, 6 months after surgery and 12 months after surgery were collected and recorded. The clinical efficacy of the two methods was compared in terms of postoperative VAS, KOOS, Lysholm score, IKDC score, knee stability (Lachman test, anterior drawer test and axial shift test), the degree of widening of bone tunnel diameter measured by CT at different stages of the postoperative period and MRI scoring system. RESULTS: At 12 months after surgery, the VAS of the measurement group was lower than that of the conventional group(P<0.001). At 12 months after surgery, KOOS scores in the measurement group were higher than those in the conventional group, and there were statistically significant differences in all scores except symptom scores (P<0.05). Six months after operation, Lysholm total score and IKDC total score in the measurement group were higher than those in the conventional group, and the difference was statistically significant (P<0.05). At 12 months after surgery, knee stability tests were performed, and the differences between the Lachman test, anterior drawer test and axial shift test measurement group and the conventional group were not statistically significant (P>0.05). However, overall knee instability analysis showed that the knee stability of the measurement group was better than that of the control group, and the difference between the groups was statistically significant (P=0.038). The imaging assessment of patients in both groups at 6 months after surgery showed that the widening of tendon tunnel diameter in both femur and tibia was reduced in the measurement group compared with the conventional group after surgery, and the difference was statistically significant(P<0.05);MRI scores were higher in all patients in the measurement group those in the conventional group, at 6 months and 12 months agter surgery(P<0.05). CONCLUSION: Arthroscopic measurement of intra-articular cavity graft length in total internal technique for ACL reconstruction, high tendon utilization, good stability, the knee joint function has recovered satisfactorily within one year, and the therapeutic effect is affirmed.

The geology and evolution of the Near-Earth binary asteroid system (65803) Didymos.

Images collected during NASA's Double Asteroid Redirection Test (DART) mission provide the first resolved views of the Didymos binary asteroid system. These images reveal that the primary asteroid, Didymos, is flattened and has plausible undulations along its equatorial perimeter. At high elevations, its surface is rough and contains large boulders and craters; at low elevations its surface is smooth and possesses fewer large boulders and craters. Didymos' moon, Dimorphos, possesses an intimate mixture of boulders, several asteroid-wide lineaments, and a handful of craters. The surfaces of both asteroids include boulders that are large relative to their host body, suggesting that both asteroids are rubble piles. Based on these observations, our models indicate that Didymos has a surface cohesion ≤ 1 Pa and an interior cohesion of ∼10 Pa, while Dimorphos has a surface cohesion of <0.9 Pa. Crater size-frequency analyzes indicate the surface age of Didymos is 40-130 times older than Dimorphos, with likely absolute ages of ~ 12.5 Myr and <0.3 Myr, respectively. Solar radiation could have increased Didymos' spin rate leading to internal deformation and surface mass shedding, which likely created Dimorphos.

Local Management for Diabetic Foot Ulcers: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: This study evaluated the efficacy of various local management strategies for diabetic foot ulcers (DFUs). BACKGROUND: Several surgical and non-surgical local interventional approaches are available for the treatment of DFUs. The comparative effectiveness of different treatments is unknown, and it remains unclear which approach is the optimal choice for DFUs treatment due to limited direct comparisons. METHODS: We did a systematic review and meta-analysis to select the optimal approach to DFUs local management. We searched Medline, Embase, Web of Science, and ClinicalTrials.gov from inception to September 1, 2023, to identify relevant randomized controlled trials (RCTs). We analysed data by pairwise meta-analyses with a random-effects model. A network meta-analysis using the surface under the cumulative ranking curve (SUCRA) was performed to evaluate the comparative efficacy of different interventional approaches in the early (within 12 wk) and late stages (over 12 wk). RESULTS: 141 RCTs involving 14076 patients and exploring 14 interventional strategies were eligible for inclusion. Most studies (102/141) had at least one risk-of-bias dimension. Good consistency was observed during the analysis. Local pairwise comparisons demonstrated obvious differences in the early-stage healing rate and early- and late-stage healing times, while no significant difference in the late-stage healing rate or adverse events were noted. SUCRAs identified the standard of care (SOC) + decellularized dressing (DD), off-loading (OL), and autogenous graft (AG) as the three most effective interventions within 12 weeks for both healing rate (97%, mean rank: 1.4; 90%, mean rank: 2.3; 80.8%, mean rank: 3.5, respectively) and healing time (96.7%, mean rank: 1.4; 83.0%, mean rank: 3.0; 76.8%, mean rank: 3.8, respectively). After 12 weeks, local drug therapy (LDT) (89.5%, mean rank: 2.4) and OL (82.4%, mean rank: 3.3) ranked the highest for healing rate, and OL (100.0%, mean rank: 1.0) for healing time. With respect to adverse events, moderate and high risks were detected in the SOC + DD (53.7%, mean rank: 7.0) and OL (24.4%, mean rank: 10.8) groups, respectively. CONCLUSION: The findings suggest that OL provided considerable benefits for DFU healing in both the early and late stages, but the high risk of adverse events warrants caution. SOC+DD may be the preferred option in the early stages, with an acceptable risk of adverse events.

A Rat Model of Middle Cerebral Artery Occlusion/Reperfusion without Damaging the Anatomical Structure of Cerebral Vessels.

Ischemic stroke stands as the primary cause of long-term disability and mortality among adults worldwide. Animal models of ischemic stroke have significantly contributed to our understanding of its pathological mechanisms and the development of potential treatments. Presently, there are two common methods involving filament (endovascular suture) techniques to induce animal models of cerebral ischemia. However, these methods have inherent limitations, such as reduced blood perfusion to the brain, damage to the external carotid artery system, impaired food and/or water intake, and sensory dysfunction of the face. This article introduces a new method for inducing a rat ischemic stroke model without compromising the cerebral vascular anatomy. In this study, the common carotid artery (CCA) of Sprague-Dawley rats was exposed, and an incision was made. A filament was then inserted through the incision into the internal carotid artery to occlude the middle cerebral artery. After 1.5 h of induced ischemia, the occluding filament was fully removed from both the internal carotid artery and the CCA. The incision in the CCA was subsequently sutured using 11-0 microsurgical sutures under a microscope (magnification 4x). Through the utilization of microsurgical techniques to repair the CCA, this study successfully developed a unique method to induce an ischemic stroke model in rats while preserving the anatomical integrity of cerebral blood vessels.

Association between monocyte to lymphocyte ratio and diabetic foot ulcer in the population of the US with diabetes based on the 1999-2004 National Health and Nutrition Examination Survey data: a retrospective cross-sectional study.

Background: Diabetic foot ulcer (DFU) is a severe complication that occurs in patients with diabetes and is a primary factor that necessitates amputation. Therefore, the occurrence and progression of DFU must be predicted at an early stage to improve patient prognosis and outcomes. In this regard, emerging evidence suggests that inflammation-related markers play a significant role in DFU. One such potential marker, the monocyte-lymphocyte ratio (MLR), has not been extensively studied in relation to DFU. This study aimed to define a connection between MLR and DFU. Methods: A cross-sectional study was conducted using National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2004. DFU was defined based on survey questionnaires assessing the presence of nonhealing ulcers in the lower extremities for more than 4 weeks in diabetes patients. The MLR was calculated as the ratio of the monocyte count to the lymphocyte count, which was directly obtained from laboratory data files. Logistic regression analysis was performed to assess the relationship between the MLR and DFU. Stratified analysis according to age, sex, body mass index, blood glucose, hemoglobin, and glycated hemoglobin categories was conducted, and multiple imputations were applied to missing data. Results: In total, 1246 participants were included; the prevalence of DFU was 9.4% (117/1246). A multivariable regression model revealed a significant association between DFU and a 0.1 unit increase in MLR after adjusting for all covariates (adjusted odds ratio=1.16, 95% confidence interval: 1.02-1.33). Subgroup analyses revealed consistent findings regarding the impact of MLR on the presence of DFU (p > 0.05). Conclusion: MLR is significantly associated with DFU in diabetes patients, and can be used as one of the indicators for predicting the occurrence of DFU. MLR assessment may be a valuable component in the follow-up of patients with diabetes.

PolyQ-expanded ataxin-2 aggregation impairs cellular processing-body homeostasis via sequestering the RNA helicase DDX6.

Ataxin-2 (Atx2) is a polyglutamine (polyQ) tract-containing RNA-binding protein, while its polyQ expansion may cause protein aggregation that is implicated in the pathogenesis of neurodegenerative diseases such as spinocerebellar ataxia type 2 (SCA2). However, the molecular mechanism underlying how Atx2 aggregation contributes to the proteinopathies remains elusive. Here, we investigated the influence of Atx2 aggregation on the assembly and functionality of cellular processing bodies (P-bodies) by using biochemical and fluorescence imaging approaches. We have revealed that polyQ-expanded (PQE) Atx2 sequesters the DEAD-box RNA helicase (DDX6), an essential component of P-bodies, into aggregates or puncta via some RNA sequences. The N-terminal like-Sm (LSm) domain of Atx2 (residues 82-184) and the C-terminal helicase domain of DDX6 are responsible for the interaction and specific sequestration. Moreover, sequestration of DDX6 may aggravate pre-mRNA mis-splicing, and interfere with the assembly of cellular P-bodies, releasing the endoribonuclease MARF1 that promotes mRNA decay and translational repression. Rescuing the DDX6 protein level can recover the assembly and functionality of P-bodies, preventing targeted mRNA from degradation. This study provides a line of evidence for sequestration of the P-body components and impairment of the P-body homeostasis in dysregulating RNA metabolism, which is implicated in the disease pathologies and a potential therapeutic target.

Combining antibiotic-loaded bone cement-based free vastus lateralis muscle-sparing flap with split-thickness skin grafts: A reliable strategy for reconstructing diabetic foot ulcers at non-weight-bearing areas.

Diabetic foot ulcers (DFUs) present significant challenges due to their associated amputation rates, mortality, treatment complexity and excessive costs. Our earlier work introduced a wound surgical integrated treatment (WSIT) for DFUs, yielding promising outcomes. This study focuses on a specific WSIT protocol employing antibiotic-loaded bone cement (ALBC) in the first Stage, and free vastus lateralis muscle-sparing (VLMS) flaps and split-thickness skin grafts (STSGs) in the second stage to repair non-weight-bearing DFUs. From July 2021 to July 2023, seven DFU patients (aged 47-71 years) underwent this treatment. Demographic data, hospital stay and repair surgery times were collected. Histological and immunohistochemical analyses assessed angiogenesis, collagen deposition and inflammation. SF-36 questionnaire measured pre- and postoperative quality of life. Preoperative ultrasound Doppler showed that the peak blood flow velocity of the recipient area artery was significantly >30 cm/s (38.6 ± 6.8 cm/s) in all patients. Muscle flap sizes varied from 8 × 3.5 × 1 to 18 × 6 × 2 cm. The operation time of the repair surgery was 156.9 ± 15.08 minutes, and the hospital stay was 18.9 ± 3.3 days. Histological analysis proved that covering DFUs with ALBC induced membrane formation and increased collagen, neovascularization and M2 macrophages fraction while reducing M1 macrophages one. All grafts survived without amputation during a 7- to 24-month follow-up, during which SF-36 scores significantly improved. A combination of ALBC with free VLMS flaps and STSGs proved to be safe and effective for reconstructing non-weight-bearing DFUs. It rapidly controlled infection, enhanced life quality and foot function, and reduced hospitalization time. We advocate integrating this strategy into DFU treatment plans.

Opsin mutants alter host plant selection by color vision in the nocturnal invasive pest Tuta absoluta.

In insects, vision is crucial in finding host plants, but its role in nocturnal insects is largely unknown. Vision involves responses to specific spectra of photon wavelengths and opsins plays an important role in this process. Long-wavelength sensitive opsin (LW opsin) and blue-sensitive opsin (BL opsin) are main visual opsin proteins and play important in behavior regulation.We used CRISPR/Cas9 technology to mutate the long-wavelength-sensitive and blue wavelength-sensitive genes and explored the role of vision in the nocturnal invasive pest Tuta absoluta. Light wave experiments revealed that LW2(-/-) and BL(-/-) mutants showed abnormal wavelength tropism. Both LW2 and BL mutations affected the preference of T. absoluta for the green environment. Mutations in LW2 and BL are necessary to inhibit visual attraction. The elimination of LW2 and BL affected the preference of leaf moths for green plants, and mutations in both induced a preference in moths for white plants. Behavioral changes resulting from LW2(-/-) and BL(-/-) mutants were not affected by sense of smell, further supporting the regulatory role of vision in insect behavior. To the best of our knowledge, this is the first study to reveal that vision, not smell, plays an important role in the host-seeking behavior of nocturnal insects at night, of which LW2 and BL opsins are key regulatory factors. These study findings will drive the development of the "vision-ecology" theory.

Ataxin-2 sequesters Raptor into aggregates and impairs cellular mTORC1 signaling.

Ataxin-2 (Atx2) is a polyglutamine (polyQ) protein, in which abnormal expansion of the polyQ tract can trigger protein aggregation and consequently cause spinocerebellar ataxia type 2 (SCA2), but the mechanism underlying how Atx2 aggregation leads to proteinopathy remains elusive. Here, we investigate the molecular mechanism and cellular consequences of Atx2 aggregation by molecular cell biology approaches. We have revealed that either normal or polyQ-expanded Atx2 can sequester Raptor, a component of mammalian target of rapamycin complex 1 (mTORC1), into aggregates based on their specific interaction. Further research indicates that the polyQ tract and the N-terminal region (residues 1-784) of Atx2 are responsible for the specific sequestration. Moreover, this sequestration leads to suppression of the mTORC1 activity as represented by down-regulation of phosphorylated P70S6K, which can be reversed by overexpression of Raptor. As mTORC1 is a key regulator of autophagy, Atx2 aggregation and sequestration also induces autophagy by upregulating LC3-II and reducing phosphorylated ULK1 levels. This study proposes that Atx2 sequesters Raptor into aggregates, thereby impairing cellular mTORC1 signaling and inducing autophagy, and will be beneficial for a better understanding of the pathogenesis of SCA2 and other polyQ diseases.

Single-cell transcriptome landscape of zebrafish liver reveals hepatocytes and immune cell interactions in understanding nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver disease in the world. Immunity is the major contributing factor in NAFLD; however, the interaction of immune cells and hepatocytes in disease progression has not been fully elucidated. As a popular species for studying NAFLD, zebrafish, whose liver is a complex immune system mediated by immune cells and non-immune cells in maintaining immune tolerance and homeostasis. Understanding the cellular composition and immune environment of zebrafish liver is of great significance for its application in NAFLD. Here, we established a liver atlas that consists of 10 cell types using single-cell RNA sequencing (scRNA-seq). By examining the heterogeneity of hepatocytes and analyzing the expression of NAFLD-associated genes in the specific cluster, we provide a potential target cell model to study NAFLD. Additionally, our analysis identified two subtypes of distinct resident macrophages with inflammatory and non-inflammatory functions and characterized the successive stepwise development of T cell subclusters in the liver. Importantly, we uncovered the possible regulation of macrophages and T cells on target cells of fatty liver by analyzing the cellular interaction between hepatocytes and immune cells. Our data provide valuable information for an in-depth study of immune cells targeting hepatocytes to regulate the immune balance in NAFLD.

THUMPD2 catalyzes the N2-methylation of U6 snRNA of the spliceosome catalytic center and regulates pre-mRNA splicing and retinal degeneration.

The mechanisms by which the relatively conserved spliceosome manages the enormously large number of splicing events that occur in humans (∼200 000 versus ∼300 in yeast) are poorly understood. Here, we show deposition of one RNA modification-N2-methylguanosine (m2G) on the G72 of U6 snRNA (the catalytic center of the spliceosome) promotes efficient pre-mRNA splicing activity in human cells. This modification was identified to be conserved among vertebrates. Further, THUMPD2 was demonstrated as the methyltransferase responsible for U6 m2G72 by explicitly recognizing the U6-specific sequences and structural elements. The knock-out of THUMPD2 eliminated U6 m2G72 and impaired the pre-mRNA splicing activity, resulting in thousands of changed alternative splicing events of endogenous pre-mRNAs in human cells. Notably, the aberrantly spliced pre-mRNA population elicited the nonsense-mediated mRNA decay pathway. We further show that THUMPD2 was associated with age-related macular degeneration and retinal function. Our study thus demonstrates how an RNA epigenetic modification of the major spliceosome regulates global pre-mRNA splicing and impacts physiology and disease.

Progress on immune dysfunction in autism spectrum disorder / 国际儿科学杂志

Autism spectrum disorder（ASD）is a serious neurodevelopmental disorder，with deficits in social and language communication，rigid behaviors，limited interests and activities. At present，research on the pathogenesis of ASD involving immunity has been making progress worldwide. In terms of cytokines（such as IL-1β，IL-8，IL-17，etc.）and ASD animal models，it has been found that the onset of ASD is associated with nervous system immune dysfunction，which may lead to synaptic function impairment. The purpose of this review is to describe the recent research on ASD and immune dysfunction to provide ideas for exploring the etiology，pathogenesis and potential therapeutic measures of ASD.

Analysis of the consistency between CTA and DSA in evaluating GLASS staging of chronic limb-threatening ischemia / 介入放射学杂志

Objective To analyze the consistency between computer tomography angiography(CTA)and digital subtraction angiography(DSA)in evaluating the global limb anatomic staging system(GLASS)stage of patients with chronic limb-threatening ischemia(CLTI).Methods The clinical data of patients with CLTI,who were admitted to the First Affiliated Hospital of Xi'an Jiaotong University of China to receive treatment between January 2017 and December 2020,were retrospectively analyzed.Taking the DSA assessment as the gold standard,the consistency of CTA and DSA in evaluating the GLASS stage of patients with CLTI was analyzed.Results In the assessment of GLASS stage of CLTI,CTA showed strong agreement with DSA.The weighted Kappa coefficient of CTA and DSA for the staging of femoropopliteal segment was 0.798(95％CI=0.722-0.873,P＜0.01),and the weighted Kappa coefficient of CTA and DSA for the staging of infrapopliteal artery segment was 0.785(95％ CI=0.725-0.845,P＜0.0l).For the overall staging of GLASS,the weighted Kappa coefficient of CTA and DSA was 0.832(95％ CI=0.752-0.91 1,P＜0.01).All the above results indicated that a very strong consistency existed between CTA and DSA in evaluating the GLASS stage of patients with CLTI.Conclusion CTA examination of lower limb can accurately evaluate GLASS score and stage of CLTI patient's target lesions,which is helpful in diagnosing lower extremity arteriosclerosis occlusion disease as well as in assessing the technical difficulty degree of its revascularization operation.(J Intervent Radiol,2024,33:300-303)