Early embryonic polarity establishment and implications for lineage differentiation.

Polarity establishment is one of the key factors affecting early embryonic development. Polarity establishment begins with myosin phosphorylation in the 8-cell embryo, and phosphorylation activates actin leading to its initiation of contractility. Subsequently, actin undergoes reorganization to form an apical domain rich in microvilli on the non-contacting surface of each blastomere, and form the actomyosin ring that marks the maturation of the apical domain in conjunction with polar protein complexes and others. From the process of polarity establishment, it can be seen that the formation of the apical domain is influenced by actin-related proteins and polar protein complexes. Some zygote genome activation (ZGA) and lineage-specific genes also regulate polarity establishment. Polarity establishment underlies the first cell lineage differentiation during early embryonic development. It regulates lineage segregation and morphogenesis by affecting asymmetric cell division, asymmetric localization of lineage differentiation factors, and activity of the Hippo signaling pathway. In this review, we systematically summarize the mechanisms of early embryonic polarity establishment and its impact on lineage differentiation in mammals, and discuss the shortcomings of the currently available studies in terms of regulatory mechanisms and species, thereby providing clues and systematic perspectives for elucidating early embryonic polarity establishment.

SIRT1: An Intermediator of Key Pathways Regulating Pulmonary Diseases.

Silent information regulator type-1 (SIRT1), a nicotinamide adenine dinucleotide+-dependent deacetylase, is a member of the sirtuins family and has unique protein deacetylase activity. SIRT1 participates in physiological as well as pathophysiological processes by targeting a wide range of protein substrates and signalings. In this review, we described the latest progress of SIRT1 in pulmonary diseases. We have introduced the basic information and summarized the prominent role of SIRT1 in several lung diseases, such as acute lung injury, acute respiratory distress syndrome, chronic obstructive pulmonary disease, lung cancer, and aging-related diseases.

Resveratrol alleviates inflammatory bowel disease by inhibiting JAK2/STAT3 pathway activity via the reduction of O-GlcNAcylation of STAT3 in intestinal epithelial cells.

The role of O-linked N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) in the pathogenesis of inflammatory bowel disease (IBD) has been increasingly highlighted in recent studies. It's been reported that signal transducer and activator of transcription 3 (STAT3) O-GlcNAcylation can affect the activity of the Janus kinase2 (JAK2)/STAT3 pathway.Our recent study showed that resveratrol repairsIBDin mice.On this basis,the present study aimed to explore whether the mechanism of IBD repair by resveratrol is associated with STAT3 O-GlcNAcylation. Pretreatment of colitis mice and intestinal epithelial cells with an O-GlcNAcylation promoter (Thiamet G, or Glucosamine) and an O-GlcNAcylation inhibitor (OSMI-1) showed that increased O-GlcNAcylation promoted colitis in mice.The pro-inflammatory cytokines interleukin (IL) -6, IL-1ß, and tumor necrosis factor-α (TNF-α) were increased, while the anti-inflammatory cytokine IL-10 was decreased. Moreover, the downstream target proteins of JAK2/STAT3, cyclooxygenase-2 and nitric oxide synthase 2 were up-regulated, Resveratrol treatment mitigated the inflammation by decreasing JAK2/STAT3 activity, as well as STAT3 O-GlcNAcylation. Finally, the correlation between STAT3 glycosylation and phosphorylation in intestinal epithelial cells under the effect of resveratrol was investigated by Immunofluorescence co-localization and immunoprecipitation.The results showed that resveratrol inhibited STAT3 O-GlcNAcylation, thereby inhibiting its phosphorylation, reducing JAK2/STAT3 pathway activity, and alleviating IBD.

Inferior vena cava hemangioma resected using a novel Toumai robotic surgical platform.

This study aims to investigate the significance of using the Toumai robotic platform for the resection of inferior vena cava (IVC) hemangiomas. Our objective is to provide information on the potential benefits of this innovative approach in managing these uncommon vascular tumors and to contribute to the growing body of knowledge in the field of surgical oncology and vascular surgery. A 37-year-old female patient with an incidental finding of a right retroperitoneal mass underwent contrast-enhanced magnetic resonance imaging, which confirmed the diagnosis of an IVC hemangioma. Due to the rarity and complexity of this vascular tumor, the medical team opted for a novel approach using the Toumai robotic surgical platform (Shanghai MicroPort MedBot Group Co, Ltd). Under general anesthesia, the patient was placed in the left lateral decubitus position, and the robotic arms were controlled remotely through the Toumai platform. A transperitoneal approach was adopted, and the surgeon meticulously resected the tumor while preserving the integrity of the IVC. The use of the Toumai robotic platform facilitated precise tumor resection, minimizing the risk of damage to surrounding structures. The minimally invasive nature of the robotic surgery contributed to a reduced incidence of postoperative complications and accelerated patient recovery. Furthermore, the remote fifth-generation mobile network surgical capabilities of the Toumai platform allow for expert care to be provided to patients despite geographic barriers. The robotic-assisted surgical approach using the Toumai platform demonstrates its potential benefits in managing rare and complex vascular tumors such as IVC hemangiomas. Robotic technology has the potential to revolutionize the field of surgical oncology and vascular surgery, leading to improved patient outcomes and healthcare delivery. However, more extensive clinical studies and larger case series are needed to validate the long-term safety and efficacy of this innovative surgical approach. Continued research and collaboration between clinicians and robotic technology experts are essential to fully realize the potential of robotic-assisted surgery for the benefit of patients with rare and challenging medical conditions.

Single-Cell Sequencing Reveals MYOF-Enriched Monocyte/Macrophage Subcluster as a Favorable Prognostic Factor in Sepsis.

This research utilized single-cell RNA sequencing to map the immune cell landscape in sepsis, revealing 28 distinct cell clusters and categorizing them into nine major types. Delving into the monocyte/macrophage subclusters, 12 unique subclusters are identified and pathway enrichment analyses are conducted using KEGG and GO, discovering enriched pathways such as oxidative phosphorylation and antigen processing. Further GSVA and AUCell assessments show varied activation of interferon pathways, especially in subclusters 4 and 11. The clinical correlation analysis reveals genes significantly linked to survival outcomes. Additionally, cellular differentiation in these subclusters is explored. Building on these insights, the differential gene expression within these subclusters is specifically scrutinized, which reveal MYOF as a key gene with elevated expression levels in the survivor group. This finding is further supported by in-depth pathway enrichment analysis and the examination of cellular differentiation trajectories, where MYOF's role became evident in the context of immune response regulation and sepsis progression. Validating the role of the MYOF gene in sepsis, a dose-dependent response to LPS in THP-1 cells and C57 mice is observed. Finally, inter-cellular communications are analyzed, particularly focusing on the MYOF+Mono/Macro subcluster, which indicates a pivotal role in immune regulation and potential therapeutic targeting.

Direct osteosynthesis in the treatment of atlas burst fractures: a systematic review.

PURPOSE: The treatment of unstable atlas fractures remains a controversial topic. The study aims at assessing the prognosis and efficacy of osteosynthesis for unstable atlas fractures through a review of the current literature and additionally aims to compare outcomes between the transoral and posterior approaches. METHODS: A systematic review of databases including PubMed, EMBASE, Cochrane, Web of Science, CNKI, and Wanfang was conducted. Titles and abstracts were screened by two reviewers to identify studies meeting pre-defined inclusion criteria for comprehensive analysis. RESULTS: The systematic review included 28 articles, 19 employing the posterior approach and 9 utilizing the transoral approach. It covered osteosynthesis in 297 patients with unstable atlas fractures, comprising 169 treated via the posterior approach and 128 via the transoral approach. Analysis revealed high healing rates and clinical improvement in both approaches, evidenced by improvements in the visual analog scale, range of motion, atlantodens interval, and lateral displacement distance post-surgery. CONCLUSION: Osteosynthesis offers effective treatment for unstable atlas fractures. Both transoral and posterior approaches can achieve good clinical outcomes for fracture, and biomechanical studies have confirmed that osteosynthesis can maintain the stability of the occipitocervical region, preserve the motor function of the atlantoaxial and occipito-atlantoaxial joints, and greatly improve the quality of life of patients. However, variations exist in the indications and surgical risks associated with each method, necessitating their selection based on a thorough clinical evaluation of the patient's condition.

Design of a novel lateral mass screw-plate system for the treatment of unstable atlas fractures: a finite element analysis.

BACKGROUND: Osteosynthesis of unstable atlas fractures preserves joint motion and therefore has a distinct advantage over a range of treatment procedures. To prevent the potential disadvantages associated with osteosynthesis, a new atlas lateral mass screw-plate (LMSP) system has been designed. However, the biomechanical role of using the LMSP system in atlas internal fixation is not known. The aim of this study was to compare the biomechanical stability of a new LMSP with traditional posterior screw and rod (PSR) fixation techniques on the occipitocervical junction (C0-C2) through finite element analysis. METHODS: A nonlinear C0-C2 finite element model of the intact upper cervical spine was developed and validated. The unstable model using the PSR system was then compared with the model using the LMSP system for fixation. A vertical load of 40 N was applied to the C0 to simulate head weight, while a torque of 1.5 Nm was applied to the C0 to simulate flexion, extension, lateral bending, and axial rotation. RESULTS: The range of motion of both systems was close to the intact model. Compared with the LMSP system model, the PSR system model increased flexion, extension, lateral bending, and axial rotation by 4.9%, 3.0%, 5.0%, and 29.5% in the C0-C1 segments, and 4.9%, 2.7%, 2.4%, and 22.6% in the C1-C2, respectively. In flexion, extension, and lateral bending motion, the LMSP system model exhibited similar stress to the PSR system model, while in axial rotation, the PSR system model exhibited higher stress. CONCLUSIONS: The findings of our study indicate that the two tested system models provide comparable stability. However, better stability was achieved during axial rotation with the LMSP system, and in this system, the maximum von Mises stress was less than that of the PSR one. As the atlantoaxial joint functions primarily as a rotational joint, the use of the LMSP system may provide a more stable environment for the joint that has become unstable due to fracture.

Antigen-induced chimeric antigen receptor multimerization amplifies on-tumor cytotoxicity.

Ligand-induced receptor dimerization or oligomerization is a widespread mechanism for ensuring communication specificity, safeguarding receptor activation, and facilitating amplification of signal transduction across the cellular membrane. However, cell-surface antigen-induced multimerization (dubbed AIM herein) has not yet been consciously leveraged in chimeric antigen receptor (CAR) engineering for enriching T cell-based therapies. We co-developed ciltacabtagene autoleucel (cilta-cel), whose CAR incorporates two B-cell maturation antigen (BCMA)-targeted nanobodies in tandem, for treating multiple myeloma. Here we elucidated a structural and functional model in which BCMA-induced cilta-cel CAR multimerization amplifies myeloma-targeted T cell-mediated cytotoxicity. Crystallographic analysis of BCMA-nanobody complexes revealed atomic details of antigen-antibody hetero-multimerization whilst analytical ultracentrifugation and small-angle X-ray scattering characterized interdependent BCMA apposition and CAR juxtaposition in solution. BCMA-induced nanobody CAR multimerization enhanced cytotoxicity, alongside elevated immune synapse formation and cytotoxicity-mediating cytokine release, towards myeloma-derived cells. Our results provide a framework for contemplating the AIM approach in designing next-generation CARs.

The influence of demographic and lifestyle factors on blood donation delay among student population: a retrospective study.

Objective: This study analysed blood donation deferral trends, reasons and demographic/lifestyle characteristics among students in Huzhou City. The aim was to understand the health status of students and reduce the deferral rate. Methods: Data on blood donation deferral among students in Huzhou City from 2018 to 2022 were collected and analysed. Deferral trends and main reasons were investigated. Using demographic and lifestyle data from 2,619 cases in 2022, a risk prediction model for deferral was constructed. Results: The deferral rate among students in Huzhou City from 2018 to 2022 was 12.60% (p = 0.000, 95%CI: 12.14-13.06%), showing a significant increasing trend. Temporary deferral was the main reason, with alanine aminotransferase (ALT), blood pressure (BP) and haemoglobin (Hb) as the main deferral factors. ALT had a deferral rate of 5.23% (4.92-5.53%), BP 3.30% (3.06-3.55%), and Hb 2.92% (2.68-3.15%). Demographic and lifestyle characteristics in 2022 showed no significant differences between education level, household registration and deferral rate (p > 0.05). However, age, sex, blood donation history, sleep quality, diet and mental state had variable effects on ALT, BP, and Hb deferrals (p < 0.05). Logistic regression showed that sex, blood donation history, sleep quality, diet and mental status were independent risk factors for ALT deferral (p < 0.05), with odds ratios (ORs) of 5.057, 2.735, 1.594, 3.679, and 1.957, respectively. Age, blood donation history, sleep quality and mental state were independent risk factors for BP deferral (p < 0.05), with ORs of 0.256, 3.658, 6.042, and 1.812, respectively. Gender, blood donation history and diet were independent risk factors for Hb deferral (p < 0.05), with ORs of 0.244, 0.542, and 3.103, respectively. Conclusion: Students' health problems require attention. Effective health education should improve self-health management and pre-donation health behaviour to encourage regular blood donation.

Dynamic Nomogram for Predicting the Risk of Perioperative Neurocognitive Disorders in Adults.

BACKGROUND: Simple and rapid tools for screening high-risk patients for perioperative neurocognitive disorders (PNDs) are urgently needed to improve patient outcomes. We developed an online tool with machine-learning algorithms using routine variables based on multicenter data. METHODS: The entire dataset was composed of 49,768 surgical patients from 3 representative academic hospitals in China. Surgical patients older than 45 years, those undergoing general anesthesia, and those without a history of PND were enrolled. When the patient's discharge diagnosis was PND, the patient was in the PND group. Patients in the non-PND group were randomly extracted from the big data platform according to the surgical type, age, and source of data in the PND group with a ratio of 3:1. After data preprocessing and feature selection, general linear model (GLM), artificial neural network (ANN), and naive Bayes (NB) were used for model development and evaluation. Model performance was evaluated by the area under the receiver operating characteristic curve (ROCAUC), the area under the precision-recall curve (PRAUC), the Brier score, the index of prediction accuracy (IPA), sensitivity, specificity, etc. The model was also externally validated on the multiparameter intelligent monitoring in intensive care (MIMIC) Ⅳ database. Afterward, we developed an online visualization tool to preoperatively predict patients' risk of developing PND based on the models with the best performance. RESULTS: A total of 1051 patients (242 PND and 809 non-PND) and 2884 patients (6.2% patients with PND) were analyzed on multicenter data (model development, test [internal validation], external validation-1) and MIMIC Ⅳ dataset (external validation-2). The model performance based on GLM was much better than that based on ANN and NB. The best-performing GLM model on validation-1 dataset achieved ROCAUC (0.874; 95% confidence interval [CI], 0.833-0.915), PRAUC (0.685; 95% CI, 0.584-0.786), sensitivity (72.6%; 95% CI, 61.4%-81.5%), specificity (84.4%; 95% CI, 79.3%-88.4%), Brier score (0.131), and IPA (44.7%), and of which the ROCAUC (0.761, 95% CI, 0.712-0.809), the PRAUC (0.475, 95% CI, 0.370-0.581), Brier score (0.053), and IPA (76.8%) on validation-2 dataset. Afterward, we developed an online tool (https://pnd-predictive-model-dynnom.shinyapps.io/ DynNomapp/) with 10 routine variables for preoperatively screening high-risk patients. CONCLUSIONS: We developed a simple and rapid online tool to preoperatively screen patients' risk of PND using GLM based on multicenter data, which may help medical staff's decision-making regarding perioperative management strategies to improve patient outcomes.

Copper-Catalyzed, Regioselective, Unsymmetrical Homocoupling of Quinoxalin-2(1H)-ones to Form C-N Homodimers.

An environmentally benign and efficient method for the synthesis of unsymmetrical diquinoxalin-2(1H)-ones with potential axial chirality via inexpensive copper-catalyzed, low-toxicity, and stable PIFA oxidation, rarely assisted by PhSeSePh, regioselective homocoupling of quinoxalin-2(1H)-ones under mild conditions is developed. This practical scheme is compatible with a variety of functional groups and allows the preparation of functionalized unsymmetrical dimeric quinoxalin-2(1H)-ones from readily available and safe starting materials, providing new ideas for the sustainable development of methodological studies of quinoxalin-2(1H)-ones.

A new, feasible, and convenient method based on semantic segmentation and deep learning for hemoglobin monitoring.

Objective: Non-invasive methods for hemoglobin (Hb) monitoring can provide additional and relatively precise information between invasive measurements of Hb to help doctors' decision-making. We aimed to develop a new method for Hb monitoring based on mask R-CNN and MobileNetV3 with eye images as input. Methods: Surgical patients from our center were enrolled. After image acquisition and pre-processing, the eye images, the manually selected palpebral conjunctiva, and features extracted, respectively, from the two kinds of images were used as inputs. A combination of feature engineering and regression, solely MobileNetV3, and a combination of mask R-CNN and MobileNetV3 were applied for model development. The model's performance was evaluated using metrics such as R2, explained variance score (EVS), and mean absolute error (MAE). Results: A total of 1,065 original images were analyzed. The model's performance based on the combination of mask R-CNN and MobileNetV3 using the eye images achieved an R2, EVS, and MAE of 0.503 (95% CI, 0.499-0.507), 0.518 (95% CI, 0.515-0.522) and 1.6 g/dL (95% CI, 1.6-1.6 g/dL), which was similar to that based on MobileNetV3 using the manually selected palpebral conjunctiva images (R2: 0.509, EVS:0.516, MAE:1.6 g/dL). Conclusion: We developed a new and automatic method for Hb monitoring to help medical staffs' decision-making with high efficiency, especially in cases of disaster rescue, casualty transport, and so on.

Serum Soluble Vascular Endothelial Growth Factor Receptor 1 as a Potential Biomarker of Hepatopulmonary Syndrome.

Background and Aims: The results of basic research implicate the vascular endothelial growth factor (VEGF) family as a potential target of hepatopulmonary syndrome (HPS). However, the negative results of anti-angiogenetic therapy in clinical studies have highlighted the need for markers for HPS. Therefore, we aimed to determine whether VEGF family members and their receptors can be potential biomarkers for HPS through clinical and experimental studies. Methods: Clinically, patients with chronic liver disease from two medical centers were enrolled and examined for HPS. Patients were divided into HPS, intrapulmonary vascular dilation [positive contrast-enhanced echocardiography (CEE) and normal oxygenation] and CEE-negative groups. Baseline information and perioperative clinical data were compared between HPS and non-HPS patients. Serum levels of VEGF family members and their receptors were measured. In parallel, HPS rats were established by common bile duct ligation. Liver, lung and serum samples were collected for the evaluation of pathophysiologic changes, as well as the expression levels of the above factors. Results: In HPS rats, all VEGF family members and their receptors underwent significant changes; however, only soluble VEGFR1 (sFlt-1) and the sFlt-1/ placental growth factor (PLGF) ratio were changed in almost the same manner as those in HPS patients. Furthermore, through feature selection and internal and external validation, sFlt-1 and the sFlt-1/PLGF ratio were identified as the most important variables to distinguish HPS from non-HPS patients. Conclusions: Our results from animal and human studies indicate that sFlt-1 and the sFlt-1/PLGF ratio in serum are potential markers for HPS.

Sodium alginate/carboxymethyl starch/κ-carrageenan enteric soft capsule: Processing, characterization, and rupture time evaluation.

Although gelatin has good characteristics in preparing soft capsules, its noticeable shortcomings force researchers to further develop substitutes for gelatin soft capsules. In this paper, sodium alginate (SA), carboxymethyl starch (CMS) and κ-carrageenan (κ-C) were used as matrix materials, and the formula of the co-blended solutions was screened through rheological method. In addition, films of the different blends were characterized by thermogravimetry analysis, SEM, FTIR, X-ray, water contact angle and mechanical properties. The results showed that κ-C had strong interaction with CMS and SA, and the mechanical properties of capsule shell were greatly improved by the addition of κ-C. When the ratio of CMS/SA/κ-C was 2:0.5:1.5, the microstructure of the films was more dense and uniform. In addition, this formula had the best mechanical properties and adhesion properties, and was more suitable for the production of soft capsules. Finally, a novel plant soft capsule was successfully prepared by dropping method, and its appearance and rupture properties met the requirements of enteric soft capsules. In simulated intestinal fluid, the soft capsules were almost completely degraded within 15 min, and they were superior to the gelatin soft capsules. Therefore, this study provides an alternative formula for preparing enteric soft capsules.

Treatment of Liver Fibrosis after Hepatitis B with TCM Combined with NAs Evaluated by Noninvasive Diagnostic Methods: A Retrospective Study.

Objective. Chronic hepatitis B liver fibrosis is an important intermediate link in the development of liver cirrhosis. A retrospective cohort study was conducted in Longhua Hospital affiliated to the Shanghai University of Traditional Chinese Medicine in order to prove whether integrated traditional Chinese and Western medicine could improve the incidence of CHB complications and clinical prognosis. There are 130 patients with hepatitis B liver fibrosis (being treated from 2011-2021) included in the study, and the patients were divided into 64 TCM users (NAs combined with TCM) and 66 TCM nonusers (NAs antiviral therapy). The serum noninvasive diagnostic model (APRI, FIB-4) and LSM value were used to classify the stages of fibrosis. The results showed that the LSM value was decreased significantly in TCM users compared with TCM nonusers (40.63% versus 28.79%). Indicators of FIB-4 and APRI of TCM users have improved significantly compared with that of TCM nonusers (32.81% versus 10.61% and 35.94% versus 24.24%). The AST, TBIL, and HBsAg levels in TCM users were lower than those in TCM nonusers, and the HBsAg level was inversely correlated with the CD3+, CD4+, and CD8+ in TCM users. The PLT and spleen thickness of TCM users also were improved considerably. The incidence rate of end-point events (decompensated cirrhosis/liver cancer) in TCM nonusers was higher than that of TCM users (16.67% versus 1.56%). The long course of the disease and a family history of hepatitis B were the risk factors for disease progression, and long-term oral administration of TCM was the protective factor. As a result, the serum noninvasive fibrosis index and imaging parameters in TCM users were lower than those of TCM nonusers. Patients in the treatment of NAs combined with TCM had better prognoses such as a lower HBsAg level, a more stable lymphocyte function, and a lower incidence of end-point events. The present findings suggest the effect of TCM combined with NAs in the treatment of chronic hepatitis B liver fibrosis is better than that of single drug treatment.

Comprehensive Bibliometric Analysis of Stem Cell Research in Alzheimer's Disease from 2004 to 2022.

INTRODUCTION: Stem cell-based regenerative medicine has provided an excellent opportunity to investigate therapeutic strategies and innovative treatments for Alzheimer's disease (AD). However, there is an absence of visual overviews to assess the published literature systematically. METHODS: In this review, the bibliometric approach was used to estimate the searched data on stem cell research in AD from 2004 to 2022, and we also utilized CiteSpace and VOSviewer software to evaluate the contributions and co-occurrence relationships of different countries/regions, institutes, journals, and authors as well as to discover research hot spots and encouraging future trends in this field. RESULTS: From 2004 to 2022, a total of 3,428 publications were retrieved. The number of publications and citations on stem cell research in AD has increased dramatically in the last nearly 20 years, especially since 2016. North America and Asia were the top 2 highest output regions. The leading country in terms of publications and access to collaborative networks was the USA. Centrality analysis revealed that the UCL (0.05) was at the core of the network. The Journal of Alzheimer's Disease (n = 102, 2.98%) was the most productive academic journal. The analyses of keyword burst detection indicated that exosomes, risk factors, and drug delivery only had burst recently. Citations and co-citation achievements clarified that cluster #0 induced pluripotent stem cells, #2 mesenchymal stem cells, #3 microglia, and #6 adult hippocampal neurogenesis persisted to recent time. CONCLUSION: This bibliometric analysis provides a comprehensive guide for clinicians and scholars working in this field. These analysis and results hope to provide useful information and references for future understanding of the challenges behind translating underlying stem cell biology into novel clinical therapeutic potential in AD.

c-Myb Dominates TBK1-Mediated Endotoxin Tolerance in Kupffer Cells by Negatively Regulating DTX4.

As a protective mechanism regulating excessive inflammation, endotoxin tolerance plays a vital role in regulating endotoxin shock. Kupffer cells are players in mediating endotoxin tolerance. Nonetheless, the regulatory mechanism regulating endotoxin tolerance is barely known. A nonclassical IKK kinase called TRAF-associated NF-κB activator (TANK)-binding kinase 1 (TBK1) can regulate inflammation. Here, we found that TBK1 is required for endotoxin tolerance in Kupffer cells. TBK1 plays a dominant role in regulating endotoxin tolerance by negatively regulating the induction of p100 processing. Deltex E3 ubiquitin ligase 4 (DTX4), a negative regulator of TBK1, can promote TBK1 K48-mediated ubiquitination and indirectly regulate endotoxin tolerance in Kupffer cells. We demonstrate that the c-Myb transcription factor could negatively regulate DTX4. Overexpression of c-Myb can be used to reduce the ubiquitination of TBK1 by reducing DTX4 transcription and to boost the anti-inflammatory effect of endotoxin tolerance. Thus, this study reveals a novel theory of TBK1-mediated endotoxin tolerance in Kupffer cells.

Recent Developments in Direct C-H Functionalization of Quinoxalin-2(1H)-Ones via Multi-Component Tandem Reactions.

The direct C-H multifunctionalization of quinoxalin-2(1H)-ones via multicomponent reactions has attracted considerable interest due to their diverse biological activities and chemical profile. This review will focus on recent achievements. It mainly covers reaction methods for the simultaneous introduction of C-C bonds and C-RF/C/O/N/Cl/S/D bonds into quinoxalin-2(1H)-ones and their reaction mechanisms. Meanwhile, future developments of multi-component reactions of quinoxalin-2(1H)-ones are envisaged, such as the simultaneous construction of C-C and C-B/SI/P/F/I/SE bonds through multi-component reactions; the construction of fused ring and macrocyclic compounds; asymmetric synthesis; green chemistry; bionic structures and other fields. The aim is to enrich the methods for the reaction of quinoxalin-2(1H)-ones at the C3 position, which have rich applications in materials chemistry and pharmaceutical pharmacology.

C1 anatomy and dimensions relative to pedicle screw placement.

The recent C1 pedicle screw technique for upper cervical vertebral stabilization allows longer screws to be implanted by setting the screw entry point through the posterior arch of C1, which could provide better biomechanics. However, there is controversy regarding the placement of C1 pedicle screws at different angles. We retrospectively reviewed the computed tomography (CT) scans of 300 patients. The trajectories of medial inclination of 0°, 5°, 10°, and 15° and trajectory of the maximum medial inclination angle were designed for each C1 pedicle on CT images. Screw track length at each angle, the angle of maximum medial inclination, pedicle height, distance from the screw entry point to the midpoint of the C1 posterior tubercle, and screw perforation rate at each angle were measured. The average maximum inclination angle was 17.01°, the maximum inclination angle screw track length was 31.05 mm, and the distance from the screw entry point to the midpoint of the C1 posterior nodule was 21.65 mm. The screw perforation rate was 46.73% at 15° of medial inclination, but only 5.61% at 10°, and no screw perforation at 5°. 26.47% C1 pedicle height < 4 mm. There was no significant difference between the measured data on the left and right sides(P > 0.05), and the measurement of female patients was usually smaller and significantly different from that of male patients(p < 0.05). Our data indicate that a reasonable screw inclination angle of 10° and the safety zone of screw angle can provide safety and avoid screw perforation. However, personalized measurement before surgery is essential.

The clinical application effects of artificial dermis scaffold and autologous split-thickness skin composite grafts combined with vacuum-assisted closure in refractory wounds.

To investigate the clinical application effects of artificial dermis scaffold and autologous split-thickness skin composite grafts combined with vacuum-assisted closure (V.A.C) in refractory wounds. A retrospective analysis was performed on 70 patients with refractory wounds admitted to the First Affiliated Hospital of Soochow University from June 2019 to December 2021 (44 males and 25 females, with an average age of 49.3 ± 21.4 years). There were 26 patients with chronic ulcers; 3 patients with cancerous wounds; 16 patients with hot crush injuries; and 25 patients with traumatic wounds, including 21 cases of hands, 33 cases of feet, 6 cases of upper limbs, and 10 cases of lower limbs. The patients were divided into an artificial dermis scaffold group (35 patients, including 21 males and 14 females, aged 49.5 ± 21.3 years) and a skin graft group (35 patients, including 23 males and 11 females, aged 49.1 ± 21.5 years). In the artificial dermis scaffold group, after debridement, the artificial dermis scaffold was transplanted for approximately 2 weeks until the wound surface was well vascularized, after which the autologous split-thick skin graft was transplanted. Negative pressure wound therapy was performed throughout the treatment. In the skin grafting group, after debridement, the autologous split-thickness skin graft (aSTSG) was transplanted, and negative pressure wound therapy was performed continuously. The wound healing rate; skin graft survival rate; postoperative wound infection; exudative fluid volume; subcutaneous haematoma; hospitalisation time; hospitalisation cost; Vancouver Scar Scale (VSS) score, used to evaluate the scar of the recipient area at 6 months after the operation; and the sensory disorder grading method, used to evaluate the sensory recovery of the recipient area, were compared between the two groups. All 70 refractory wounds healed. In the artificial dermis scaffold group, the skin graft survival rate was 90% (86%-95%), the hospitalisation time was 38 (29-45) days, the hospitalisation cost was 148 102 (118242-192327) yuan, and the VSS score was 1.9 ± 1.3. There were significant differences in skin graft survival rate (70% [60%-80%]), length of hospital stay (21 [14-28] days), hospitalisation cost (76 201 [39228-135 919] yuan) and VSS score [6.1 ± 3.6] between the skin graft group and the artificial dermis scaffold group (P < .05). The skin graft survival rate, scar hyperplasia and sensory recovery of the recipient area in the artificial dermis scaffold group were better than those in the skin graft group, but the hospitalisation time was relatively longer, and the hospitalisation cost was relatively higher. Wound healing rate, postoperative wound infection, exudate volume, and subcutaneous haematoma of patients in the two groups were similar, and there were no significant differences (P > .05). The artificial dermis scaffold and composite transplantation of autologous aSTSG with V.A.C can promote painless wound healing and improve the skin survival rate, skin colour and lustre, and flexible smooth texture and is conducive to less scar hyperplasia and postoperative functional exercise and recovery. This method provides a reasonable and effective scheme for the treatment of clinical refractory wounds.