Anterior cruciate ligament femoral side retained stump technique reduces enlargement of the femoral bone tunnel after anterior cruciate ligament reconstruction.

BACKGROUND: Enlargement of the bone tunnel has become an unavoidable early complication after anterior cruciate ligament (ACL) reconstruction, whether it is a single or double-bundle ACL reconstruction. Preservation of the ACL stump in ACL reconstruction reduces enlargement of the bone tunnel. The purpose of this study was to investigate the question of whether single-bundle ACL reconstruction using the ACL femoral side retained stump technique reduces enlargement of the femoral tunnel. METHODS: Forty patients who underwent single-bundle reconstruction of the ACL were included in this study. The patients were categorized into a Remnant preservation group (Group R) and the Non-remnant preservation group (Group N). In the Remnant preservation group, a high-flexion femoral side retained stump technique was used intraoperatively for the establishment of the femoral side bone tunnel, and in the Non-remnant preservation group, the conventional femoral positioning method was used (we used a femoral positioning drill for localization and drilling of the femoral bone tunnel), and MRI of the operated knee joints was performed at 6 months postoperatively. We measured the internal diameter of the femoral bone tunnel at 5 mm from the intra-articular outlet of the femoral bone tunnel on an MRI scan image perpendicular to the femoral bone tunnel. The size of the tunnel was compared between the intraoperative drilling of the bone tunnel and the size of the bone tunnel at 6 months postoperatively. Postoperative clinical assessment was Lysholm score. RESULTS: After a 6-month follow-up of 40 patients, the diameter of the femoral tunnel at a distance of 5 mm from the inner opening of the femoral tunnel was 10.96 ± 0.67 mm and 10.11 ± 0.62 mm in patients of group N and group R, respectively, and the difference was statistically significant (P < 0.05).The diameter of the femoral tunnel at 6 months postoperatively in group N and group R compared to the intraoperative bone tunnel increased by 2.58 ± 0.24 mm and 1.94 ± 0.31 mm, and the difference was statistically significant (P < 0.05).The femoral tunnel enlargement rates of group N and group R were 30.94 ± 3.00% and 24.02 ± 5.10%, respectively, and the differences were significant (P < 0.05). CONCLUSION: ACL femoral side retained stump technique does not sacrifice the ideal location of the femoral tunnel and is able to preserve the possible benefits of the ACL stump: reduced femoral tunnel enlargement.

Effects of Geo-Stress and Natural Fracture Strength on Hydraulic Fracture Propagation in a Deep Fractured Tight Sandstone Reservoir.

Hydraulic fracturing technology has been widely used in the tight reservoir reconstruction. Unfortunately, with the deepening of mining depth and the increase of geo-stress, the propagation mechanism of medium-pressure fractures in the reservoir is significantly different from that of conventional shallow reservoirs. Based on the combined finite discrete element method, this paper conducts numerical simulation research on deep tight sandstone reservoirs in the west. The discrete fracture network modeling method is used to establish a tight sandstone reservoir model with natural bedding, and the influence of geo-stress difference and natural fracture strength on hydraulic fracture propagation law in a high geo-stress environment is discussed in detail. The results show that the difference between geo-stress and the strength of natural fractures has a significant effect on the shape and expansion of hydraulic fractures under the high geo-stress conditions. The greater the difference in ground stress, the more obvious the tendency of the main fractures of the reservoir, and the shorter the branch fractures. With the increase of natural fracture strength, the changes in propagation pressure, fracture length, area, and width, which can be fitted with a linear function with a goodness of fit as high as 0.99. In addition, the morphological results of hydraulic fractures in the simulation are not only affected by the constitutive parameters of the model but also may be affected by the randomness of the natural fracture network, thus, showing a certain degree of dispersion. Therefore, it is extremely necessary to build a reservoir fracturing model in a specific area based on more detailed geological monitoring data to guide actual construction. The above achievements have certain reference significance for the field operation of deep tight sandstone reservoirs.

[Research progress of femoral bone tunnel positioning in anterior cruciate ligament reconstruction].

Objective: To review the concept and methods of femoral bone tunnel positioning in anterior cruciate ligament (ACL) reconstruction, in order to provide a reference for clinical treatment. Methods: The relevant literature on the concept and methods of femoral bone tunnel positioning in ACL reconstruction in domestic and international research was extensively reviewed. Results: The position of the femoral bone tunnel is a key factor in determining the prognosis of ACL reconstruction. The concept of femoral bone tunnel positioning in ACL reconstruction has experienced isometric reconstruction, anatomical reconstruction, Ribbon-like theory, I.D.E.A.L. theory, and nearly isometric reconstruction theory. The femoral bone tunnel positioning technique is also changing with the in-depth study of the anatomy and biomechanics of the ACL, and each bone tunnel positioning technique has its own advantages and disadvantages. Over-The-Top technique is now mainly used for ACL revision; the clock-face positioning method is basically no longer applicable due to the large error, poor stability, and low retrievability; the bone landmarks positioning method (the lateral condyle of the femur's Resident's ridge and bifurcation ridge, and the the apex of the deep cartilage), which is now mostly used clinically due to the more constant anatomical landmarks. The quadrant method under X-ray fluoroscopy is more cumbersome to implement intraoperatively, so it is mainly used for academic research; computer navigation-assisted positioning has gradually become popular in recent years, which is highly accurate, avoids the influence of human factors on the positioning of the bone tunnel, and has a very good prospect of application; three-dimensional printing-assisted positioning technology, which is accurate in positioning, with a high degree of reproducibility and a short learning curve. Conclusion: The concept of femoral bone tunnel positioning for ACL reconstruction has undergone several evolutions, reflecting the deepening of the understanding of ACL and the improvement of the clinical results of reconstruction. The precision, personalization, and intelligence of positioning techniques are the focus of current and future development.

Coronavirus disease-2019 and orthopedics: A bibliometric analysis of the literature.

BACKGROUND: The coronavirus disease-2019 (COVID-19) pandemic has had a dramatic impact on global health, with orthopedics among the most affected specialties. An increasing number of COVID-19-related orthopedic studies have been published. The purpose of this study was to analyze the orthopedic literature published during the COVID-19 pandemic to guide future research. METHODS: The Scopus database was searched for relevant literature published between 2020 and 2022. The keywords used in the retrieval process were ("COVID-19" OR "Coronavirus" OR "2019-nCoV" OR "SARS-CoV-2" OR "Betacoronavirus" OR "novel coronavirus 2019" OR "novel coronavirus" OR "coronavirus-19" OR "COVID 19" OR "nCOV" OR "COVID-2019" OR "COVID 2019") and ("orthopedic" OR "orthopedics" OR "orthopedic" OR "orthopedical" OR "orthopedical" OR "orthopedics"). Spreadsheet software (Excel, Microsoft Corp., Redmond, WA) was used to analyze the top 10 cited authors, countries, journals, and articles. The top 5 publication types were also analyzed. VOSviewer (Center for Science and Technology Studies, Leiden, Netherlands) was used to network and visualize the literature. RESULTS: A total of 1619 publications relevant to COVID-19 and orthopedics were reviewed. Among these publications, the most active country, author, and publication type included the United States, Vaishya R, and original articles, respectively. The most frequently used keywords were human, coronavirus disease-2019, pandemic, and orthopedics. The Journal of Bone and Joint Surgery American Volume was the most cited journal, whereas the greatest number of articles was published in the Journal of Clinical Orthopedics and Trauma. CONCLUSIONS: This study provides a perspective on the development of orthopedic publications during the COVID-19 pandemic and evidence for researchers worldwide to strengthen global cooperation in fighting the epidemic.

Bone morphogenetic protein signaling inhibitor improves differentiation and function of 3D muscle construct fabricated using C2C12.

Functional tissue-engineered artificial skeletal muscle tissue has great potential for pharmacological and academic applications. This study demonstrates an in vitro tissue engineering system to construct functional artificial skeletal muscle tissues using self-organization and signal inhibitors. To induce efficient self-organization, we optimized the substrate stiffness and extracellular matrix (ECM) coatings. We modified the tissue morphology to be ring-shaped under optimized self-organization conditions. A bone morphogenetic protein (BMP) inhibitor was added to improve overall myogenic differentiation. This supplementation enhanced the myogenic differentiation ratio and myotube hypertrophy in two-dimensional cell cultures. Finally, we found that myotube hypertrophy was enhanced by a combination of self-organization with ring-shaped tissue and a BMP inhibitor. BMP inhibitor treatment significantly improved myogenic marker expression and contractile force generation in the self-organized tissue. These observations indicated that this procedure may provide a novel and functional artificial skeletal muscle for pharmacological studies.

Osteomyelitis of the femur caused by Metamycoplasma orale in an immunocompromised patient using metagenomic next-generation sequencing: A case report.

Background: Metamycoplasma orale (M.orale), a symbiotic bacterium observed in the human oral cavity, is generally regarded as non-pathogenic to humans. Although infrequent, symptomatic infections caused by M.orale may occur in individuals with compromised humoral immunity. Accurate identification and early diagnosis of M.orale still present significant challenges due the limitations associated with conventional detection methods. Although metagenomic next-generation sequencing (mNGS) is currently widely utilized in clinical practices and exhibits a remarkable specificity and sensitivity for detecting various pathogens, its application in the diagnosis of M.orale-induced osteomyelitis remains largely unexplored. Case description: In this report, we present a case study of osteonecrosis caused by M.orale in a 20-year-old female patient with nephrotic syndrome and other comorbidities. She was administered long-term hormone therapy and immunosuppressants, leading to her admission to the hospital due to recurrent fever, hip abscess and left thigh pain. Imaging examination revealed bilateral mid-femoral lesions, with the extensive nature of the left femoral lesion suggesting a potential secondary infection. Although no pathogen was detected in pus culture, mNGS analysis identified M.orale in the sample. Following treatment with doxycycline and levofloxacin, the patient's symotoms improved and she was discharged with favorable outcomes. Conclusion: mNGS enables rapid identification of etiology in patients with osteomyelitis caused by the rare pathogen M.orale. This case accentuate the strength of mNGS for early detection and targeted clinical treatment of infectious diseases caused by uncommon pathogens.

Euchromatin histone-lysine N-methyltransferase 2 regulates the expression of potassium-sodium-activated channel subfamily T member 1 in primary sensory neurons and contributes to remifentanil-induced pain sensitivity.

Intraoperative remifentanil administration has been linked to increased postoperative pain sensitivity. Recent studies have identified the involvement of euchromatic histone-lysine N-methyltransferase 2 (Ehmt2/G9a) in neuropathic pain associated with the transcriptional silencing of many potassium ion channel genes. This study investigates whether G9a regulates the potassium sodium-activated channel subfamily T member 1 (Slo2.2) in remifentanil-induced post-incisional hyperalgesia (RIH) in rodents. We performed remifentanil infusion (1 µg·kg-1·min-1 for 60 min) followed by plantar incision to induce RIH in rodents. Our results showed that RIH was accompanied by increased G9a and H3K9me2 production and decreased Slo2.2 expression 48 h postoperatively. Deletion of G9a rescued Slo2.2 expression in DRG and reduced RIH intensity. Slo2.2 overexpression also reversed this hyperalgesia phenotype. G9a overexpression decreased Slo2.2-mediated leak current and increased excitability in the small-diameter DRG neurons and laminal II small-diameter neurons in the spinal dorsal horn, which was implicated in peripheral and central sensitization. These results suggest that G9a contributes to the development of RIH by epigenetically silencing Slo2.2 in DRG neurons, leading to decreased central sensitization in the spinal cord. The findings may have implications for the development of novel therapeutic targets for the treatment of postoperative pain.

High flexion femoral side remnant preservation positioning technique: a new method for positioning the femoral tunnel in anterior cruciate ligament reconstruction.

PURPOSE: The aim of this study is to find a new method for femoral side preservation positioning in anterior cruciate ligament (ACL) reconstruction and test the accuracy and precision of this method. METHOD: Fifty patients with isolated ACL rupture (42 males and 8 females) who underwent single-bundle ACL reconstruction in our hospital between July 2022 and July 2023 were included. The lowest point of the cartilage margin of the lateral wall of the intercontinental fossa and the tibial plateau plumb line at 120° of knee flexion were used as the anatomical landmarks for positioning of the femoral tunnel for ACL reconstruction surgery. Femoral side remnant preservation was performed in all cases. Three-dimensional CT was performed 3 days postoperatively to collect the data, which were analyzed using Mimics 21.0 software. We measured the posterior cortical distance of the femoral condyle at 90° of knee flexion and the vertical distance from the center of the bone tunnel to the cortical extension line behind the femur. All femoral tunnel positions were marked on a 4 × 4 grid and visualized using the quadrant method. RESULTS: Using the new positioning method in 50 knees, the average distance of x was 25.26 ± 2.76% of t and the average distance of y was 23.69 ± 6.19% of h. This is close to the results of previous studies, where x was 24.2 ± 4.0% of t and the average distance of y was 21.6 ± 5.2% of h. Most femoral tunnel positions were located in the same area. The D values were distributed as follows: 60% in the range of 0 to 2 mm, 24% in the range of 2 to 4 mm, and 16% more than 4 mm. The E values were distributed as follows: 80% in the range of 0 to 4 mm and 20% more than 4 mm. CONCLUSION: In arthroscopic ACL reconstruction, the knee was flexed at 120° and the lowest point of the cartilage edge of the lateral wall of the intercondylar fossa and the tibial plateau plumb line were used as anatomical landmarks for the positioning of the femoral bone tunnel, which resulted in more accurate femoral bone tunnel positioning, better reproducibility, and better preservation of the femoral stump compared to traditional positioning methods.

The first pineoblastoma case report of a patient with Sotos syndrome harboring NSD1 germline mutation.

Germline mutations of NSD1 are associated with Sotos syndrome, characterized by distinctive facial features, overgrowth, and developmental delay. Approximately 3% of individuals with Sotos syndrome develop tumors. In this study, we describe an infant in pineoblastoma with facial anomalies, learning disability and mild autism at 1 years diagnosed as Sotos syndrome owing to carrying a novel mutation de novo germline NSD1 likely pathogenic variant. This patient expands both the mutation and phenotype spectrum of the Sotos Syndrome and provides new clinical insights into the potential mechanism of underlying pinealoblastoma pathology.

Nanopore targeted sequencing-based diagnosis of central nervous system infections in HIV-infected patients.

BACKGROUND: Early and accurate etiological diagnosis is very important for improving the prognosis of central nervous system (CNS) infections in human immunodeficiency virus (HIV)-infected patients. The goal is not easily achieved by conventional microbiological tests. We developed a nanopore targeted sequencing (NTS) platform and evaluated the diagnostic performance for CNS infections in HIV-infected patients, with special focus on cryptococcal meningitis (CM). We compared the CM diagnostic performance of NTS with conventional methods and cryptococcal polymerase chain reaction (PCR). METHODS: This study included 57 hospitalized HIV-infected patients with suspected CNS infections from September 2018 to March 2022. The diagnosis established during hospitalization includes 27 cases of CM, 13 CNS tuberculosis, 5 toxoplasma encephalitis, 2 cytomegalovirus (CMV) encephalitis and 1 Varicella-zoster virus (VZV) encephalitis. The 2 cases of CMV encephalitis also have co-existing CM. Target-specific PCR amplification was used to enrich pathogen sequences before nanopore sequencing. NTS was performed on stored cerebrospinal fluid (CSF) samples and the results were compared with the diagnosis during hospitalization. RESULTS: 53 (93.0%) of the patients were male. The median CD4 cell count was 25.0 (IQR: 14.0-63.0) cells/uL. The sensitivities of CSF culture, India ink staining, cryptococcal PCR and NTS for CM were 70.4% (95%CI: 51.5 - 84.1%), 76.0% (95%CI: 56.6 - 88.5%), 77.8% (59.2 - 89.4%) and 85.2% (95%CI: 67.5 - 94.1%), respectively. All those methods had 100% specificity for CM. Our NTS platform could identify Cryptococcus at species level. Moreover, NTS was also able to identify all the 5 cases of toxoplasma encephalitis, 2 cases of CMV encephalitis and 1 VZV encephalitis. However, only 1 of 13 CNS tuberculosis cases was diagnosed by NTS, and so did Xpert MTB/RIF assay. CONCLUSIONS: NTS has a good diagnostic performance for CM in HIV-infected patients and may have the ability of simultaneously detecting other pathogens, including mixed infections. With continuing improving of the NTS platform, it may be a promising alterative microbiological test for assisting with the diagnosis of CNS infections.

Subtype recognition and identification of a prognosis model characterized by antibody-dependent cell phagocytosis-related genes in breast cancer.

BACKGROUND: Breast cancer (BC) is a heterogeneous tumor with a variety of etiology and clinical features. Antibody-dependent cell phagocytosis (ADCP) is the last step of immune checkpoint inhibition (ICI), and macrophages detect and recognize tumor cells, then destroy and engulf tumor cells. Despite the large number, negative regulators that inhibit phagocytic activity are still a key obstacle to the full efficacy of ICI. PATIENTS AND METHODS: An ADCP-related risk score prognostic model for risk stratification as well as prognosis prediction was established in the Cancer Genome Atlas (TCGA) cohort. The predictive value of ADCP risk score in prognosis and immunotherapy was also further validated in the TCGA along with International Cancer Genome Consortium cohorts. To promote the clinical application of the risk score, a nomogram was established, with its effectiveness verified by different methods. RESULTS: In this study, the genes collected from previous studies were defined as ADCP-related genes. In BC patients, two ADCP-related subtypes were identified. The immune characteristics and prognostic stratification were significant different between them. CONCLUSIONS: We identified two subtypes associated with ADCP gene expression in breast cancer. They have significant differences in immune cells, molecular functions, HLA family genes, immune scores, stromal scores, and inflammatory gene expression, which have important guiding significance for the selection of clinical treatment methods. At the same time, we constructed a risk model based on ADCP, and the risk score can be used as a good indicator of prognosis, providing potential therapeutic advantages for chemotherapy and immunotherapy, thus helping the clinical decision-making of BC patients.

A peptide from the Japanese encephalitis virus failed to induce the production of anti-N-methyl-d-aspartate receptor antibodies via molecular mimicry in mice.

Background: The development of anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis following viral encephalitis, such as Japanese encephalitis, has received increasing attention in recent years. However, the mechanism of anti-NMDAR antibody production following Japanese encephalitis has not been explored. Methods: A peptide from the Japanese encephalitis virus (JEV), which shares a similar amino acid sequence with GluN1, was identified by sequence comparison. We then explored whether active subcutaneous immunization with the JEV peptide could induce the production of anti-NMDAR antibodies and related pathophysiological and behavioral changes in mice. In addition, a published active immune model of anti-NMDAR encephalitis using a GluN1 peptide was used as the positive control. Results: A 6-amino-acid sequence with 83 % similarity between the envelope protein of the JEV (HGTVVI) and GluN1 (NGTHVI) was identified, and the sequence included the N368/G369 region. Active immunization with the JEV peptide induced a substantial and specific immune response in mice. However, anti-NMDAR antibodies were not detected in the serum of mice immunized with the JEV peptide by ELISA, CBA, and TBA. Moreover, mice immunized with the JEV peptide presented no abnormities related to anti-NMDAR antibodies according to western blotting, patch clamp, and a series of behavioral tests. In addition, active immunization with a recently reported GluN1 peptide failed to induce anti-NMDAR antibody production in mice. Conclusions: In this study, the attempt of active immunization with the JEV peptide to induce the production of anti-NMDAR antibodies via molecular mimicry failed. The pathogenesis of anti-NMDAR encephalitis following Japanese encephalitis remains to be elucidated.

Autophagy alleviates hippocampal neuroinflammation by inhibiting the NLRP3 inflammasome in a juvenile rat model exposed particulate matter.

Ambient fine particulate matter (PM) is a global public and environmental problem. PM is closely associated with several neurological diseases, which typically involve neuroinflammation. We investigated the impact of PM exposure on neuroinflammation using both in vivo (in a juvenile rat model with PM exposure concentrations of 1, 2, and 10 mg/kg for 28 days) and in vitro (in BV-2 and HT-22 cell models with PM concentrations of 50-200 µg/ml for 24 h). We observed that PM exposure induced the activation of the NLRP3 inflammasome, leading to the production of IL-1ß and IL-18 in the rat hippocampus and BV-2 cells. Furthermore, inhibition of the NLRP3 inflammasome with MCC950 effectively reduced neuroinflammation and ameliorated hippocampal damage. In addition, autophagy activation was observed in the hippocampus of PM-exposed rats, and the promotion of autophagy by rapamycin (Rapa) effectively attenuated the NLRP3-mediated neuroinflammation induced by PM exposure. However, autophagic flow was blocked in BV-2 cells exposed to PM, and Rapa failed to ameliorate NLRP3 inflammasome activation. We found that autophagy was activated in HT-22 cells exposed to PM and that treatment with Rapa reduced the release of reactive oxygen species (ROS) and malondialdehyde (MDA), as well as cell apoptosis. In a subsequent coculture model of BV-2 and HT-22 cells, we observed the activation of the NLRP3 inflammasome in BV-2 cells when the HT-22 cells were exposed to PM, and this activation was alleviated when PM-exposed HT-22 cells were pretreated with Rapa. Overall, our study revealed that PM exposure triggered hippocampal neuroinflammation by activating the NLRP3 inflammasome. Notably, autophagy mitigated NLRP3 inflammasome activation, potentially by reducing neuronal ROS and apoptosis. This research emphasized the importance of reducing PM exposure and provided valuable insight into its neurotoxicity.

DIA-based quantitative proteomics analysis of plasma exosomes in rat model of allergic rhinitis.

Allergic rhinitis (AR) is a common chronic inflammatory disease characterized by symptoms such as itching, rhinorrhea, sneezing, and nasal obstruction. Despite being classified as an IgE-mediated typeⅠ allergy for many years, the complex pathophysiological mechanism of AR continues to present a challenge in clinical management. The objective of this study was to quantify the proteomics of plasma exosomes using data independent acquisition (DIA) in combination with liquid chromatography-mass spectrometry (LC-MS/MS) to identify the key proteins involved in the development and progression of AR. In the AR rat model, a total of 41 proteins demonstrated significant up-regulation, while 51 proteins were found to be significantly down-regulated. Gene ontology (GO) analysis results indicated that the altered proteins were highly enriched in cellular regulatory processes and enzymatic activity in AR rats. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein-protein interaction (PPI) network results revealed that the pivotal proteins C4b, C1qa, C1qc, and Mbl1 might be involved in the metabolic pathways of the immune system in AR through the activation of the complement and coagulation cascades pathway. These proteins could serve as diagnostic markers and therapeutic targets for AR, which is of great significance in understanding the role of exosome proteins in AR.

Ambient particulate matter exposure induces ferroptosis in hippocampal cells through the GSK3B/Nrf2/GPX4 pathway.

Epidemiological studies have established a robust correlation between exposure to ambient particulate matter (PM) and various neurological disorders, with dysregulation of intracellular redox processes and cell death being key mechanisms involved. Ferroptosis, a cell death form characterized by iron-dependent lipid peroxidation and disruption of antioxidant defenses, may be involved in the neurotoxic effects of PM exposure. However, the relationship between PM-induced neurotoxicity and ferroptosis in nerve cells remains to be elucidated. In this study, we utilized a rat model (exposed to PM at a dose of 10 mg/kg body weight per day for 4 weeks) and an HT-22 cell model (exposed to PM at concentrations of 50, 100, and 200 µg/mL for 24 h) to investigate the potential induction of ferroptosis by PM exposure. Furthermore, RNA sequencing analysis was employed to identify hub genes that potentially contribute to the process of ferroptosis, which was subsequently validated through in vivo and in vitro experiments. The results revealed that PM exposure increased MDA content and Fe2+ levels, and decreased SOD activity and GSH/GSSG ratio in rat hippocampal and HT-22 cells. Through RNA sequencing analysis, bioinformatics analysis, and RT-qPCR experiments, we identified GSK3B as a possible hub gene involved in ferroptosis. Subsequent investigations demonstrated that PM exposure increased GSK3B levels and decreased Nrf2, and GPX4 levels in vivo and in vitro. Furthermore, treatment with LY2090314, a specific inhibitor of GSK3B, was found to mitigate the PM-induced elevation of MDA and ROS and restore SOD activity and GSH/GSSG ratio. The LY2090314 treatment promoted the upregulation of Nrf2 and GPX4 and facilitated the nuclear translocation of Nrf2 in HT-22 cells. Moreover, treatment with LY2090314 resulted in the upregulation of Nrf2 and GPX4, along with the facilitation of nuclear translocation of Nrf2. This study suggested that PM-induced ferroptosis in hippocampal cells may be via the GSK3B/Nrf2/GPX4 pathway.

Melanin-Inspired Composite Materials: From Nanoarchitectonics to Applications.

Synthetic melanin is a mimic of natural melanin analogue with intriguing properties such as metal-ion chelation, redox activity, adhesion, and broadband absorption. Melanin-inspired composite materials are formulated by assembly of melanin with other types of inorganic and organic components to target, combine, and build up the functionality, far beyond their natural capabilities. Developing efficient and universal methodologies to prepare melanin-based composite materials with unique functionality is vital for their further applications. In this review, we summarize three types of synthetic approaches, predoping, surface engineering, and physical blending, to access various melanin-inspired composite materials with distinctive structure and properties. The applications of melanin-inspired composite materials in free radical scavenging, bioimaging, antifouling, and catalytic applications are also reviewed. This review also concludes current challenges that must be addressed and research opportunities in future studies.

Copper Catalyst-Promoted Regioselective Multicomponent Cascade Cyclization of 3-Aza-1,5-enynes with Sulfur Dioxide and Cycloketone Oxime Esters to Access Cyanoalkylsulfonylated 1,2-Dihydropyridines.

Radical cascade cyclization via the cracking of alkenyl C-H has emerged as an attractive and remarkable tool for the rapid construction of ring frameworks with endocyclic double bonds. We developed a cascade reaction of 3-aza-1,5-enynes with sulfur dioxide and cycloketone oxime esters to access cyanoalkylsulfonylated 1,2-dihydropyridines, which can be easily converted to pyridine derivatives. This protocol involves radical addition to the C≡C bond and 6-endo cyclization and features high regioselectivity and a broad substrate scope.

The locus coeruleus-dorsal hippocampal CA1 pathway is involved in depression-induced perioperative neurocognitive disorders in adult mice.

BACKGROUND: Patients undergoing surgical anesthesia increasingly suffer from preoperative depression. Clinical studies have shown that depression is a risk factor for perioperative neurocognitive disorders (PNDs) in elder patients. However, the underlying mechanism, especially at the neural circuit level, remains poorly understood. METHODS: Right carotid artery separation under sevoflurane and chronic social defeat stress (CSDS) in adult mice were used to establish surgical anesthesia and chronic depression models. Cognitive function was assessed by the Y maze and novel object recognition tests. A chemogenetic approach was used to modulate the locus coeruleus-dorsal hippocampal CA1 (LC-dCA1) circuit. Hippocampal synaptic alterations were evaluated by Golgi staining and whole-cell patch clamp recording. RESULTS: We found that CSDS induced synaptic impairments in dorsal hippocampal CA1 pyramidal neurons and cognitive deficits in adult mice after surgery under sevoflurane. Chemogenetic activation of the LC-dCA1 pathway significantly alleviated the CSDS-induced synaptic impairments and cognitive dysfunction. On the contrary, inhibition of this pathway could mimic CSDS-induced deficits. Furthermore, we showed that dopamine played an important role in CSDS-induced PNDs in adult mice after surgery/sevoflurane. CONCLUSION: Overall, our results have demonstrated a vital role for the LC-dCA1 pathway in CSDS-induced PNDs in adult mice undergoing surgery with sevoflurane anesthesia.

Autoimmune encephalitis antibody profiles and clinical characteristics of children with suspected autoimmune encephalitis.

AIM: To identify the spectrum of autoimmune encephalitis antibody biomarkers (AE-Abs) in children with suspected autoimmune encephalitis and explore the clinical features indicating AE-Abs presence. METHOD: We included children with suspected autoimmune encephalitis who underwent AE-Abs tests at the Children's Hospital of Chongqing Medical University between June 2020 and June 2022. Clinical features suggestive of AE-Abs were analysed based on AE-Abs test results. RESULTS: A total of 392 children were tested for AE-Abs with suspected autoimmune encephalitis. Of these, 49.5% were male, with a median age of 7 years 11 months (6 months-17 years 11 months); 93.6% (367/392) of all patients had both serum and cerebrospinal fluid (CSF) tests performed. The antibody-positive rate in the cohort was 23.7% (93/392), the serum antibody-positive rate was 21.9% (84/384), and the CSF antibody-positive rate was 20.8% (78/375). Eleven different AE-Abs were detected. Serum analysis revealed that N-methyl-D-aspartate receptor immunoglobulin-G (NMDAR-IgG) (15.1%) was greater than myelin oligodendrocyte glycoprotein (MOG)-IgG (14.6%) and glial fibrillary acidic protein (GFAP)-IgG (3.3%). CSF analysis revealed that NMDAR-IgG (16.3%) was greater than MOG-IgG (13.8%) and GFAP-IgG (3.3%). Compared with antibody-negative patients, antibody-positive patients were more often female (odds ratio [OR] 1.86, p = 0.03), with memory impairment (OR 2.91, p = 0.01) and sleep disorders (OR 2.08, p = 0.02). INTERPRETATION: In children, the most frequent AE-Abs detected were NMDAR-IgG and MOG-IgG. Female sex, memory impairment, and sleep disorders predict a higher likelihood of AE-Abs.

Identification of novel proteins for sleep apnea by integrating genome-wide association data and human brain proteomes.

BACKGROUND: Sleep apnea is regarded as a significant global public health issue. The relationship between sleep apnea and nervous system diseases is intricate, yet the precise mechanism remains unclear. METHODS: In this study, we conducted a comprehensive analysis integrating the human brain proteome and transcriptome with sleep apnea genome-wide association study (GWAS), employing genome-wide association study (PWAS), transcriptome-wide association study (TWAS), Mendelian randomization (MR), and colocalization analysis to identify brain proteins associated with sleep apnea. RESULTS: The discovery PWAS identified six genes (CNNM2, XRCC6, C3orf18, CSDC2, SQRDL, and DGUOK) whose altered protein abundances in the brain were found to be associated with sleep apnea. The independent confirmatory PWAS successfully replicated four out of these six genes (CNNM2, C3orf18, CSDC2, and SQRDL). The transcriptome level TWAS analysis further confirmed two out of the four genes (C3orf18 and CSDC2). The subsequent two-sample Mendelian randomization provided compelling causal evidence supporting the association of C3orf18, CSDC2, CNNM2, and SQRDL with sleep apnea. The co-localization analysis further supported the association between CSDC2 and sleep apnea (posterior probability of hypothesis 4 = 0.75). CONCLUSIONS: In summary, the integration of brain proteomic and transcriptomic data provided multifaceted evidence supporting causal relationships between four specific brain proteins (CSDC2, C3orf18, CNNM2, and SQRDL) and sleep apnea. Our findings provide new insights into the molecular basis of sleep apnea in the brain, promising to advance understanding of its pathogenesis in future research.