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Objectives: Ottelia Pers. is in the Hydrocharitaceae family. Species in the genus are aquatic, and China is their centre of origin in Asia. Ottelia alismoides (L.) Pers., which is distributed worldwide, is a distinguishing element in China, while other species of this genus are endemic to China. However, O. alismoides is also considered endangered due to habitat loss and pollution in some Asian countries. Ottelia alismoides is the only submerged macrophyte that contains three carbon dioxide-concentrating mechanisms, i.e. bicarbonate (HCO3−) use, crassulacean acid metabolism and the C4 pathway. In this study, we present its first genome assembly to help illustrate the various carbon metabolism mechanisms and to enable genetic conservation in the future. Data description: Using DNA and RNA extracted from one O. alismoides leaf, this work produced ∼ 73.4 Gb HiFi reads, ∼ 126.4 Gb whole genome sequencing short reads and ∼ 21.9 Gb RNA-seq reads. The de novo genome assembly was 6,455,939,835 bp in length, with 11,923 scaffolds/contigs and an N50 of 790,733 bp. Genome assembly completeness assessment with Benchmarking Universal Single-Copy Orthologs revealed a score of 94.4%. The repetitive sequence in the assembly was 4,875,817,144 bp (75.5%). A total of 116,176 genes were predicted. The protein sequences were functionally annotated against multiple databases, facilitating comparative genomic analysis. [ABSTRACT FROM AUTHOR]

The Huanglian-Hongqu herb pair (HH) is a carefully crafted traditional Chinese herbal compound designed to address disorders related to glucose and lipid metabolism. Its primary application lies in treating hyperlipidemia and fatty liver conditions. This study explored the potential mechanism of HH in treating non-alcoholic fatty liver disease (NAFLD) through network pharmacology, molecular docking, and in vivo animal experiments. Ultrahigh performanceliquid chromatography-quadrupole/orbitrapmass spectrometry (UPLC-Q-TOF-MS) was employed to identify the chemical composition of HH. Network pharmacology was used to analyze the related signaling pathways affected by HH. Subsequently, the prediction was verified by animal experiment. Finally, we identified 29 components within HH. Network pharmacology unveiled interactions between HH and 153 NAFLD-related targets, highlighting HH's potential to alleviate NAFLD through NF-κB signaling pathway. Molecular docking analyses illuminated the binding interactions between HH components and key regulatory proteins, including NF-κB, NLRP3, ASC, and Caspase-1. In vivo experiments demonstrated that HH alleviated NAFLD by reducing serum and liver lipid levels, improving liver function, and lowering inflammatory cytokine levels in the serum. Moreover, HH administration downregulated mRNA and protein levels of the NF-κB/NLRP3 pathway. In conclusion, our findings demonstrated that HH has potential therapeutic benefits in ameliorating NAFLD by targeting the NF-κB/NLRP3 pathway, facilitating the broader application of HH in the field of NAFLD. [ABSTRACT FROM AUTHOR]

The Huanglian-Hongqu herb pair (HH) is a carefully crafted traditional Chinese herbal compound designed to address disorders related to glucose and lipid metabolism. Its primary application lies in treating hyperlipidemia and fatty liver conditions. This study explored the potential mechanism of HH in treating non-alcoholic fatty liver disease (NAFLD) through network pharmacology, molecular docking, and in vivo animal experiments. Ultrahigh performanceliquid chromatography-quadrupole/orbitrapmass spectrometry (UPLC-Q-TOF-MS) was employed to identify the chemical composition of HH. Network pharmacology was used to analyze the related signaling pathways affected by HH. Subsequently, the prediction was verified by animal experiment. Finally, we identified 29 components within HH. Network pharmacology unveiled interactions between HH and 153 NAFLD-related targets, highlighting HH's potential to alleviate NAFLD through NF-κB signaling pathway. Molecular docking analyses illuminated the binding interactions between HH components and key regulatory proteins, including NF-κB, NLRP3, ASC, and Caspase-1. In vivo experiments demonstrated that HH alleviated NAFLD by reducing serum and liver lipid levels, improving liver function, and lowering inflammatory cytokine levels in the serum. Moreover, HH administration downregulated mRNA and protein levels of the NF-κB/NLRP3 pathway. In conclusion, our findings demonstrated that HH has potential therapeutic benefits in ameliorating NAFLD by targeting the NF-κB/NLRP3 pathway, facilitating the broader application of HH in the field of NAFLD. [ABSTRACT FROM AUTHOR]

Background: The prevalence and distinction between first Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and reinfection with the Omicron variant among healthcare workers (HCWs) remain unclear. Methods: A cross-sectional study was conducted at a hospital in Southern China. The study included 262 HCWs who were infected with SARS-CoV-2 between April and June 2023, with 101 cases of first infection and 161 ones of reinfection. Student’s t-test, Analysis of Variance (ANOVA), and Mann-Whitney U tests were used based on the distribution of quantitative variables. Pearson’s chi-square and Fisher’s exact tests were used based on the expected frequencies of categorical variables. Results: The reinfection rate among HCWs was 11.5% (161/1406). The majority of the infected HCWs were female (212/262, 80.9%, first infection vs. reinfection: 76.2% vs. 83.9%). The nursing staff, had the highest percentage of SARS-CoV-2 infection (42.0%), especially of its reinfection (47.8%). Out of the 262 infected individuals, 257 had received SARS-CoV-2 vaccination, primarily inactivated vaccines (243/257, 91.1%). The first infection group, which received four doses (24, 23.8%), was significantly higher than that in the reinfection group (6, 3.7%) (P < 0.001). The proportion of asymptomatic infections among HCWs in the two groups was 1.0% and 1.2%. The main symptoms during the first infection and reinfection were fever (83.2% and 50.9%) and sore throat (78.2% and 77.0%). There were significant differences in the prevalence of fever (83.2% vs. 50.9%), rhinorrhea (45.5% vs. 60.9%) and myalgia (56.4% vs. 37.9%) between the first infection and reinfection (P < 0.05). The average interval for SARS-CoV-2 reinfection was 149.9 (range: 114–182, SD = 11.9) days. Notably, physicians had the shortest average interval of 142.8 (8.8) days, while management and administrative staff had the longest average interval of 153.8 (13.5) days. Conclusions: Although the symptoms of HCWs during reinfection with SARS-CoV-2 were milder, the high reinfection rate and short interval between infections indicate the need to enhance monitoring and protective measures for HCWs during the epidemic. [ABSTRACT FROM AUTHOR]

Purpose: Poor ovarian response (POR) is a big challenge for in vitro fertilization. The traditional Chinese medicine, Cai's Prescription of Tonifying Kidney and Strengthening Vitals (Cai's Prescription) has yielded satisfactory results for POR treatment clinically, but systematic scientific research of Cai's Prescription is not well reported. This study aimed to investigate the clinical effect of Cai's Prescription on poor ovarian responders and its biological mechanism. Methods: Serum was collected from poor ovarian responders, and IL-1β, INFγ, FSH, E2 and AMH levels were analyzed by ELISA. Ovarian antral follicles were identified and counted using transvaginal ultrasound. The embryo quality grading were done on day 3 after retrieval. We used high-throughput sequencing of granulosa cells to investigate the gene transcription patterns of ovarian granulosa cells in poor ovarian responders after Cai's Prescription pretreatment. The expression level of ARHGAP4 was analyzed by quantitative real-time PCR and western blot. The effects of ARHGAP4 for granulosa cells were analyzed by CCK-8 assay, annexin-V and PI staining, ELISA and western blot. The effects of Cai's Prescription on the expression of PI3K-Akt pathway and apoptosis were analyzed by western blot. Results: In this study, we found that Cai's Prescription pretreatment had the tendency to improve the ovarian reserve function and could increase the number of high quality embryos for poor ovarian responders. Through high-throughput sequencing of mRNA in granulosa cells, we discovered ARHGAP4, which is a member of GTPase-activating proteins (GAPs) may be a candidate target for POR treatment. ARHGAP4 was significantly increased in poor ovarian responders and can be recovered after Cai's Prescription pretreatment. Mechanically, combining the cell line model and clinical tissue samples, we found that ARHGAP4 can accelerate cell apoptosis and inflammation response in granulosa cells via PI3K-Akt signaling pathway. In addition, Cai's Prescription pretreatment for three months significantly reduced the high level of ARHGAP4 in poor ovarian responders. Conclusion: This study shows that the traditional Chinese medicine, Cai's Prescription yielded satisfactory results for poor ovarian responders clinically and ARHGAP4 may be a candidate target for POR treatment. [ABSTRACT FROM AUTHOR]

Large skin wounds are one of the most important health problems in the world. Skin wound repair and tissue regeneration are complex processes involving many physiological signals, and effective wound healing remains an enormous clinical challenge. Therefore, there is an urgent need for a strategy to rapidly kill bacteria, promote cell proliferation and accelerate wound healing. At present, electrical stimulation (ES) is often used in the clinical treatment of skin wounds and can simulate the endogenous biological current of the body and accelerate the repair process of skin wounds. However, a single ES strategy has difficulty covering the entire wound area, which may lead to unsatisfactory therapeutic effects. To overcome this deficiency, it is essential to develop a collaborative treatment strategy that combines ES with other treatments. In this study, gold nanoparticles and antibacterial peptides (Os) were loaded on the surface of poly(lactic-co-glycolic acid) (PLGA) material through the reducibility and adhesion of polydopamine (PDA) and improved the electrical activity, anti-inflammatory, antibacterial and biocompatibility properties of the polymer material. At the same time, this composite membrane material (Os/Au-PDA@PLGA) combined with ES was used in wound therapy to improve the wound healing rate. The results show that the new wound repair material has good biocompatibility and can effectively promote cell proliferation and migration. Through the combined application of gold nanoparticles and antibacterial peptides Os, the polymer materials have more efficient bactericidal and antioxidant effects. The antibacterial experiment results showed that gold nanoparticles could further enhance the antibacterial activity of antibacterial peptides. Furthermore, the Os/Au-PDA@PLGA composite membrane has good hydrophilicity and electrical activity, which can provide a more favorable cell microenvironment for wound healing. In vivo studies using a full-thickness skin defect model in rats showed that the Os/Au-PDA@PLGA composite membrane had a better therapeutic effect than the pure PLGA material. More importantly, the combination of the Os/Au-PDA@PLGA composite with ES significantly accelerated the rate of vascularization and collagen deposition and promoted wound healing compared with non-ES controls. Therefore, the combination of the Au/Os-PDA@PLGA composite membrane with ES may provide a new strategy for the effective treatment of skin wounds. [ABSTRACT FROM AUTHOR]

Objective: Full endoscopic techniques are being gradually introduced from single-segment cervical disc herniation surgery to two-segment cervical disc herniation surgery. However, there is no suitable full endoscopic treatment for mixed-type two-segment cervical disc herniation (MTCDH) in which one segment herniates in front of the spinal cord and the other segment herniates behind the spinal cord. Therefore, we introduce a new full endoscopic technique by combining an anterior transcorporeal approach and a posterior translaminar approach. In addition, we provide a brief description of its safety, efficacy, feasibility, and surgical points. Methods: Thirty patients with MTCDH were given full endoscopic surgical treatment by a combined transcorporeal and transforaminal approach and were followed up for at least 12 months. Results: Clinical assessment scales showed that the patient's symptoms and pain were significantly reduced postoperatively. Imaging results showed bony repair of the surgically induced bone defect and the cervical Cobb angle was increased. No serious complications occurred. Conclusion: This technique enables minimally invasive surgery to relieve the compression of the spinal cord by MTCDH. It avoids the fusion of the vertebral body for internal fixation, preserves the vertebral motion segments, avoids medical destruction of the cervical disc to the greatest extent possible, and expands the scope of adaptation of full endoscopic technology in cervical surgery. [ABSTRACT FROM AUTHOR]

Background: To investigate the clinical application of modified Crain classification in anterior cruciate ligament (ACL) reconstruction (ACLR) with remnant preservation.Methods: The subjects were 70 patients with ACL injury who underwent ACLR from May 2016 to June 2018, and their general data were recorded. They were randomly divided into modified remnant-preserved ACLR group (group M, n = 35) and non remnant-preserved ACLR group (group N, n = 35). ACLR program with remnant preservation was designed based on modified Crain classification in group M, while ACL remnants were completely cleaned during ACLR in group N. Subsequently, the two groups were compared in terms of operation time, complications, as well as Lysholm score, international knee documentation committee (IKDC) score and positive rate of Lachman test of knee joint before operation and at 3, 6 and 12 months after operation.Results: Both the groups showed good postoperative efficacy, and none had complications like limited knee extension or cyclops lesion. The comparison results found that group M (72.49 ± 7.64 min) required longer operation time than group N (66.06 ± 6.37 min) (P < 0.05). Lysholm score and IKDC score at 3, 6 and 12 months after operation in the two groups were significantly higher than those before operation (P < 0.05); group M had higher Lysholm score and IKDC score at 3 months and 6 months after operation compared with group N (P < 0.05). Additionally, the positive rate of Lachman test at 3, 6 and 12 months after operation in both groups was significantly lower than that before operation (P < 0.05), but there was no significant difference between group M and group N.Conclusion: With the modified Crain classification, many remnant-preserved reconstruction techniques can be rationally used to completely preserve the remnant ligament tissue during operation and improve knee joint function and joint stability with few complications. [ABSTRACT FROM AUTHOR]

Background: To investigate the clinical application of modified Crain classification in anterior cruciate ligament (ACL) reconstruction (ACLR) with remnant preservation. Methods: The subjects were 70 patients with ACL injury who underwent ACLR from May 2016 to June 2018, and their general data were recorded. They were randomly divided into modified remnant-preserved ACLR group (group M, n = 35) and non remnant-preserved ACLR group (group N, n = 35). ACLR program with remnant preservation was designed based on modified Crain classification in group M, while ACL remnants were completely cleaned during ACLR in group N. Subsequently, the two groups were compared in terms of operation time, complications, as well as Lysholm score, international knee documentation committee (IKDC) score and positive rate of Lachman test of knee joint before operation and at 3, 6 and 12 months after operation. Results: Both the groups showed good postoperative efficacy, and none had complications like limited knee extension or cyclops lesion. The comparison results found that group M (72.49 ± 7.64 min) required longer operation time than group N (66.06 ± 6.37 min) (P < 0.05). Lysholm score and IKDC score at 3, 6 and 12 months after operation in the two groups were significantly higher than those before operation (P < 0.05); group M had higher Lysholm score and IKDC score at 3 months and 6 months after operation compared with group N (P < 0.05). Additionally, the positive rate of Lachman test at 3, 6 and 12 months after operation in both groups was significantly lower than that before operation (P < 0.05), but there was no significant difference between group M and group N. Conclusion: With the modified Crain classification, many remnant-preserved reconstruction techniques can be rationally used to completely preserve the remnant ligament tissue during operation and improve knee joint function and joint stability with few complications. [ABSTRACT FROM AUTHOR]

Background: Implantable collamer lens implantation (ICL) is a form of 'foldable' posterior chamber phakic intraocular lens refractive surgery that generally does not impair cornea and natural accommodation. The potential advantages of the ICL over keratorefractive laser procedures include less induction of higher-order aberrations (HOAs) and enhanced retinal image magnification. On the other hand, small incision lenticule extraction (SMILE), currently, one of the most popular refractive surgery procedures, also offers excellent visual outcomes, particularly for eyes with low to moderate amounts of myopia. The aim of this study is to evaluate whether ICL/TICL (toric ICL) is comparable to SMILE for low to moderate myopia in terms of refractive outcomes at 3 and 18 months post-operatively.Methods/design: This is a prospective randomized study. A total of 300 participants will be randomized into two groups, the ICL/TICL group and SMILE group. Eligible participants with spherical equivalent (SE) less than - 6.0 diopter (D) will be recruited. Following randomization, participants will be followed at 1, 3, 6, 12, and 18 months. The primary outcome is the refractive predictability at every postoperative point after surgery, which is the proportion of the number of eyes achieving a postoperative SE within ± 0.5 D and ± 1.0 D of the intended target. Secondary outcome parameters include visual acuity, refraction, adverse events, and quality of vision measurements.Discussion: This trial will provide information on whether ICL has comparable, if not superior, refractive outcomes compared to the established SMILE for low to moderate myopia, thus providing evidence for translation into clinical practice.Trial Registration: Chinese clinical trial registry (ChiCTR) 2200055372. Registered on 08 January 2022. [ABSTRACT FROM AUTHOR]

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating condition that can lead to severe impairment of physical, psychological, cognitive, social, and occupational functions. The cause of ME/CFS remains incompletely understood. There is no clinical diagnostic test for ME/CFS. Although many therapies have been used off-label to manage symptoms of ME/CFS, there are limited, if any, specific therapies or cure for ME/CFS. In this study, we investigated the expression of genes specific to key immune functions, and viral infection status in ME/CFS patients with an aim of identifying biomarkers for characterization and/or treatment of the disease.Methods: In 2021, one-hundred and sixty-six (166) patients diagnosed with ME/CFS and 83 healthy controls in the US participated in this study via a social media-based application (app). The patients and heathy volunteers consented to the study and provided self-collected finger-stick blood and first morning void urine samples from home. RNA from the fingerstick blood was tested using DxTerity's 51-gene autoimmune RNA expression panel (AIP). In addition, DNA from the same fingerstick blood sample was extracted to detect viral load of 4 known ME/CFS associated viruses (HHV6, HHV7, CMV and EBV) using a real-time PCR method.Results: Among the 166 ME/CFS participants in the study, approximately half (49%) of the ME/CFS patients reported being house-bound or bedridden due to severe symptoms of the disease. From the AIP testing, ME/CFS patients with severe, bedridden conditions displayed significant increases in gene expression of IKZF2, IKZF3, HSPA8, BACH2, ABCE1 and CD3D, as compared to patients with mild to moderate disease conditions. These six aforementioned genes were further upregulated in the 22 bedridden participants who suffer not only from ME/CFS but also from other autoimmune diseases. These genes are involved in T cell, B cell and autoimmunity functions. Furthermore, IKZF3 (Aiolos) and IKZF2 (Helios), and BACH2 have been implicated in other autoimmune diseases such as systemic lupus erythematosus (SLE) and Rheumatoid Arthritis (RA). Among the 240 participants tested with the viral assays, 9 samples showed positive results (including 1 EBV positive and 8 HHV6 positives).Conclusions: Our study indicates that gene expression biomarkers may be used in identifying or differentiating subsets of ME/CFS patients having different levels of disease severity. These gene targets may also represent opportunities for new therapeutic modalities for the treatment of ME/CFS. The use of social media engaged patient recruitment and at-home sample collection represents a novel approach for conducting clinical research which saves cost, time and eliminates travel for office visits. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the presence and change of nerve fibers and neuropeptide during early development of articular cartilage in neonatal rats. Methods: Articular cartilage in distal-femoral epiphyses was collected from neonatal Sprague Dawley rats, which were 1-day, 5-day, and 10-day postnatal (P1, P5 and P10). Microscopy, immunofluorescence, transmission and scanning electron microscopy (TEM and SEM) were performed for detection of nerve fibers. Quantitative analysis for substance P (SP) and neuropeptide Y (NPY) was conducted using immunofluorescence and enzyme-linked immunosorbent assay (ELISA). Results: TEM showed the existence of myelinated nerve fibers in the extracellular matrix of articular cartilage in both P1, P5 and P10 rats, and they formed synaptic contacts with chondrocytes. During this time, chondrocytes proceeded with their development, and the nerve fibers gradually degraded. The ELISA results showed significant increase of the sensory neuropeptide SP and the sympathetic neuropeptide NPY in the cartilage tissue. Immunofluorescence results showed the distribution of SP and NPY in the perichondrium, the cartilage canals, the plasma of chondrocytes, and extracellular matrix in the cartilage tissue. Conclusions: Nerve fibers exist in the matrix of articular cartilage during early development of knee joints in neonatal rats. Nerve fibers form synaptic contacts with chondrocytes at the early stage and then degrade gradually in the course of chondrocyte development. SP and NPY significantly increase in articular cartilage during this very period. These results indicate that the nerve fibers and the neuropeptide they secrete may exert important effect on the development of articular cartilage. [ABSTRACT FROM AUTHOR]

Early detection can benefit cancer patients with more effective treatments and better prognosis, but existing early screening tests are limited, especially for multi-cancer detection. This study investigated the most prevalent and lethal cancer types, including primary liver cancer (PLC), colorectal adenocarcinoma (CRC), and lung adenocarcinoma (LUAD). Leveraging the emerging cell-free DNA (cfDNA) fragmentomics, we developed a robust machine learning model for multi-cancer early detection. 1,214 participants, including 381 PLC, 298 CRC, 292 LUAD patients, and 243 healthy volunteers, were enrolled. The majority of patients (N = 971) were at early stages (stage 0, N = 34; stage I, N = 799). The participants were randomly divided into a training cohort and a test cohort in a 1:1 ratio while maintaining the ratio for the major histology subtypes. An ensemble stacked machine learning approach was developed using multiple plasma cfDNA fragmentomic features. The model was trained solely in the training cohort and then evaluated in the test cohort. Our model showed an Area Under the Curve (AUC) of 0.983 for differentiating cancer patients from healthy individuals. At 95.0% specificity, the sensitivity of detecting all cancer reached 95.5%, while 100%, 94.6%, and 90.4% for PLC, CRC, and LUAD, individually. The cancer origin model demonstrated an overall 93.1% accuracy for predicting cancer origin in the test cohort (97.4%, 94.3%, and 85.6% for PLC, CRC, and LUAD, respectively). Our model sensitivity is consistently high for early-stage and small-size tumors. Furthermore, its detection and origin classification power remained superior when reducing sequencing depth to 1× (cancer detection: ≥ 91.5% sensitivity at 95.0% specificity; cancer origin: ≥ 91.6% accuracy). In conclusion, we have incorporated plasma cfDNA fragmentomics into the ensemble stacked model and established an ultrasensitive assay for multi-cancer early detection, shedding light on developing cancer early screening in clinical practice. [ABSTRACT FROM AUTHOR]

Background: There are a variety of internal fixation methods for unstable femoral neck fractures (FNFs), but the best method is still unclear. Femoral neck system (FNS) is a dynamic angular stabilization system with cross screws, and is a new internal fixation implant designed for minimally invasive fixation of FNFs. In this study, we conducted a biomechanical comparison of FNS, InterTan nail and three cannulated screws for the treatment of Pauwels III FNFs and investigate the biomechanical properties of FNS.Methods: A total of 18 left artificial femurs were selected and randomly divide into Group A (fixation with FNS), Group B (fixation with InterTan nail) and Group C (fixation with three cannulated screws), with 6 specimens in each group. After creating Pauwels type III FNF models, the specimens in each were tested with non-destructive quasi-static tests, including torsion, A-P bending and axial compression tests. The average slope of the linear load-deformation curve obtained from quasi-static tests defines the initial torsional stiffness, A-P bending stiffness, and axial compression stiffness. After cyclic loading test was applied, the overall deformation of models and local deformation of implant holes in each group were assessed. The overall deformation was estimated as the displacement recorded by the software of the mechanical testing apparatus. Local deformation was defined as interfragmental displacement. Data were analyzed by one-way analysis of variance (ANOVA) followed by Bonferroni post hoc test using the SPSS software (version 24.0, IBM, New York, NY, USA). Correlation analysis was performed using Pearson's correlation analysis.Results: Group B exhibited significantly higher axial stiffness and A-P bending stiffness than the other two groups (P < 0.01), while Group A had significantly higher axial stiffness and A-P bending stiffness than Group C (P < 0.01). Groups A and B exhibited significantly higher torsional stiffness than Group C (P < 0.01), no statistical significance was observed between Groups A and B (P > 0.05). Group B exhibited significantly lower overall and local deformations than the other two groups (P < 0.01), while Group A had significantly lower overall and local deformations than Group C (P < 0.01). Correlation analysis revealed positive correlation between axial stiffness and A-P bending stiffness (r = 0.925, P < 0.01), torsional stiffness (r = 0.727, P < 0.01), between torsional stiffness and A-P bending stiffness; negative correlation between overall, local deformations and axial stiffness (r = - 0.889, - 0.901, respectively, both P < 0.01), and positive correlation between the two deformations (r = - 0.978, P < 0.01).Conclusion: For fixation of unstable FNFs, InterTan nail showed the highest axial stiffness and A-P bending stiffness, followed by FNS, and then three cannulated screws. Torsional stiffness of FNS was comparable to that of the InterTan nail. FNS, as a novel minimally invasive implant, can create good mechanical environment for the healing of unstable FNFs. Clinical studies are needed to confirm the potential advantages of FNS observed in this biomechanical study. [ABSTRACT FROM AUTHOR]

Background: Circular RNAs (circRNAs) are involved in regulatory processes of ubiquitination and deubiquitination in various tumors at post-transcriptional epigenetic modification level. However, the underlying mechanism and its biological functions of circRNAs in the advanced laryngeal squamous cell carcinoma (LSCC) remain obscure. Methods: RNA sequencing and quantitative real-time PCR (qRT-PCR) assays were applied to screen for circRNAs differentially expressed in LSCC tissues and cell lines. The candidate RNA-binding proteins and target signalling pathway were detected by RNA pull-down and mass spectrometry, in situ hybridization (ISH), immunohistochemistry (IHC), qRT-PCR assays, and bioinformatics analysis. The functional roles of these molecules were investigated using in vitro and in vivo experiments including EdU, transwell, wound healing, western blot assays, and the xenograft mice models. The molecular mechanisms were identified using RNA pull-down assays, RNA immunoprecipitation (RIP), Co-IP, ISH, Ubiquitination assay, bioinformatics analysis, and the rescue experiments. Results: Here, we unveil that microtubule cross-linking factor 1 circRNA (circMTCL1, circ0000825) exerts its critical oncogenic functions by promoting complement C1q-binding protein (C1QBP)-dependent ubiquitin degradation and subsequently activating Wnt/β-catenin signalling in laryngeal carcinoma initiation and development. Specifically, circMTCL1 was remarkably up-regulated in the paired tissues of patients with LSCC (n = 67), which predicted a worse clinical outcome. Functionally, circMTCL1 exerted oncogenic biological charactersistics by promoting cell proliferative capability and invasive and migrative abilities. Ectopic circMTCL1 augumented cell proliferation, migration, and invasion of LSCC cells, and this effect could be reversed by C1QBP knocking down in vitro and in vivo. Mechanistically, circMTCL1 directly recruited C1QBP protein by harboring the specific recognized sequence (+ 159 − + 210), thereby accelerating the translation of C1QBP expression by inhibiting its ubiquitin–proteasome-mediated degradation. Importantly, the direct interaction of C1QBP with β-catenin protein was enhanced via suppressing the β-catenin phosphorylation and accelerating its accumulation in cytoplasm and nucleus. Conclusion: Our findings manifested a novel circMTCL1-C1QBP-β-catenin signaling axis involving in LSCC tumorigenesis and progression, which shed new light on circRNAs-ubiquitous acidic glycoprotein mediated ubiquitin degradation and provided strategies and targets in the therapeutic intervention of LSCC. [ABSTRACT FROM AUTHOR]

Background: Mechanical loading has been widely considered to be essential for growth plate to maintain metabolism and development. Cyclic mechanical strain has been demonstrated to induce autophagy, whereas the relationship between cyclic tensile strain (CTS) and autophagy in growth plate chondrocytes (GPCs) is not clear. The objective of this study was to investigate whether CTS can regulate autophagy in GPCs in vitro and explore the potential mechanisms of this regulation. Methods: The 2-week-old Sprague–Dawley rat GPCs were subjected to CTS of varying magnitude and duration at a frequency of 2.0 Hz. The mRNA levels of autophagy-related genes were measured by RT-qPCR. The autophagy in GPCs was verified by transmission electron microscopy (TME), immunofluorescence and Western blotting. The fluorescence-activated cell sorting (FACS) was employed to detect the percentage of apoptotic and necrotic cells. Results: In GPCs, CTS significantly increased the mRNA and protein levels of autophagy-related genes, such as LC3, ULK1, ATG5 and BECN1 in a magnitude- and time-dependent manner. There was no significant difference in the proportion of apoptotic and necrotic cells between control group and CTS group. The autophagy inhibitors, 3-methyladenine (3MA) and chloroquine (CQ) reversed the CTS-induced autophagy via promoting the formation of autophagosomes. Cytochalasin D (cytoD), an inhibitor of G-actin polymerization into F-actin, could effectively block the CTS-induced autophagy in GPCs. Conclusion: Cyclic mechanical strain with high-tensile triggers autophagy in GPCs, which can be suppressed by 3MA and CQ, and cytoskeletal F-actin microfilaments organization plays a key role in chondrocytes' response to mechanical loading. [ABSTRACT FROM AUTHOR]

Background: Left displacement of the third gastric compartment (LDC3) in alpacas is an extremely rare condition and has not been reported thus far. Therefore, we describe the clinical diagnosis and treatment of LDC3 in an alpaca. Case presentation: A 2-year-old brown female alpaca (Vicugna pacos) was presented to evaluate a 3-day history of abdominal distension causing loss of both appetite and thirst, along with oliguria and low to no defecation. Clinical examination, X-ray examination, surgical exploration, and determination of gastric pH (pH ~ 2.35) confirmed that LDC3 resulted in abdominal distension. The gastric wall of the displaced third gastric compartment was incised for the expulsion of pneumatosis, and a medical-grade silicone tube was inserted into the incision to remove the effusion by siphoning. Surgical treatment proved to effectively alleviate the abdominal distension caused by LDC3 without apparent side effects. Conclusions: To our knowledge, this case is the first known report of LDC3 in an alpaca in China. A similar condition, left displaced abomasum, has previously been described in cattle and sheep. [ABSTRACT FROM AUTHOR]

Background: Our research was designed to decide whether the application of C2 pars screws is an alternative choice for patients with OPLL involving the C2 segment.Methods: A total of 40 patients who underwent cervical laminectomy with fusion (LF) from C2 to C6 for OPLL were reviewed. Among them, C2 pedicle screws were placed in 23 patients, who were the pedicle group, and C2 pars screws were placed in 17 patients, who were the pars group. The screw placement and vertebral artery (VA) anatomy presented by standard CT. General clinical characteristics and health-related outcomes were evaluated and compared preoperatively and during the follow-up period.Results: The Pars group tended to have a shorter operation duration and less blood loss than the pedicle group (operation time: 115.29 ± 28.75 vs 133.48 ± 26.22, p = 0.044; blood loss: 383.53 ± 116.19 vs 457.83 ± 145.45, p = 0.039). Operation time and blood loss were both independently related to the pars group (operation time: OR = 0.966, p = 0.021; blood loss: OR = 0.993, p = 0.046). The idealization and acceptability of C2 screws in the pars group exceeded those in the pedicle group (100% vs 91.3%). However, no statistically obvious variation in the included complications or health-related outcomes between the pedicle and pars groups was observed.Conclusion: In the treatment of patients with OPLL involving the C2 segment, the application of C2 pars screws is an alternative choice, which is not only safer but also reduces the amount of blood loss, shortens the operation time and obtains a more ideal screw placement. [ABSTRACT FROM AUTHOR]

Titanium (Ti) implants are widely used in dentistry and orthopedics owing to their excellent corrosion resistance, biocompatibility, and mechanical properties, which have gained increasing attention from the viewpoints of fundamental research and practical applications. Also, numerous studies have been carried out to fine-tune the micro/nanostructures of Ti and/or incorporate chemical elements to improve overall implant performance. Zinc oxide nanoparticles (nano-ZnO) are well-known for their good antibacterial properties and low cytotoxicity along with their ability to synergize with a variety of substances, which have received increasingly widespread attention as biomodification materials for implants. In this review, we summarize recent research progress on nano-ZnO modified Ti-implants. Their preparation methods of nano-ZnO modified Ti-implants are introduced, followed by a further presentation of the antibacterial, osteogenic, and anti-corrosion properties of these implants. Finally, challenges and future opportunities for nano-ZnO modified Ti-implants are proposed. [ABSTRACT FROM AUTHOR]

Background: Human adenovirus (HAdV) had been recognized as one of the most common enteric viruses associated with acute diarrhea in children. The present study was carried out to demonstrate the molecular and epidemiological characterization of HAdV Infections among children in Shandong province in China between July 2017 and June 2018. Methods: Fecal specimens were collected from children under 5 years old with acute diarrhea. DNA was extracted from the stool specimens and adenovirus DNA was detected by PCR amplification with specific primers. The amplification products were subjected to electrophoresis and visualized on a UV transilluminator. All positive RT-PCR amplification products were sequenced and the obtained sequences analyzed by MEGA (version 7.0). Demographic information and clinical manifestation data were also analyzed. Results: In total, 656 fecal specimens were collected and the overall positive rate of HAdV was 7.47%. HAdV infections were detected in all age groups, in which children aged 13–24 months presented the highest positive rate. Seasonal pattern could be observed with a peak in December, January and February. Diarrhea, vomiting, dehydration and fever were the main clinical manifestations, in which vomiting was the most common accompanied symptom. By phylogenetic analysis, four species (A, B, C, and F) were detected and seven different serotypes were identified. HAdV-41 (48.98%, 24/49) was the most common serotype followed by HAdV-3 (18.37%, 9/49), HAdV-31 (14.29%, 7/49), HAdV-7 (8.16%, 4/49), HAdV-40 (4.08%, 2/49), HAdV-1 (4.08%, 2/49) and HAdV-2 (2.04%, 1/49). Conclusion: This study indicated that HAdV infection was an important cause of acute diarrhea among children under 5 years old in Shandong province. The results will contribute to (a) increase understanding of the role of HAdV in diarrheal children and enhance identification of the predominant diarrhea pathogen for diagnosis; (b) avoid abuse of antibiotics; (c) monitor the change of prevalent HAdV serotypes and promote vaccine development and vaccination. [ABSTRACT FROM AUTHOR]

Background: To explore the clinical effect of laminectomy alone and laminectomy with instrumentation in the treatment of TOLF.Methods: A retrospective study was conducted on the clinical data of 142 patients with TOLF and laminectomy who underwent spine surgery at XXX Medical University from January 2003 to January 2018. According to whether the laminectomy was combined with instrumentation, the patients were divided into two groups: group A (laminectomy alone (LA), n = 77) and group B (laminectomy with instrumentation (LI), n = 65). Comparisons of possible influencing factors of demographic variables and operation-related variables were carried out between the two groups. In this study, the clinical effects of LA and LI in the treatment of TOLF were discussed. Thus, we explored the clinical effect of LA and LI in the treatment of TOLF.Results: In terms of demographics, there was a statistically significant difference in BMI between group A and group B (P < 0.05). The differences in age, sex, smoking, drinking, heart disease, hypertension and diabetes were not statistically significant (P > 0.05). In terms of preoperative symptoms, there was a significant difference in gait disturbance, pain in the LE, and urination disorder between group A and group B (P < 0.05), but there was no significant difference in other variables between the two groups (P > 0.05). In terms of operation-related variables, there was a significant difference in the preoperative duration of symptoms, intramedullary signal change on MRI, dural ossification, residual rate of cross-sectional spinal canal area on CT, shape on the sagittal MRI, operation time, pre-mJOA, post-mJOA at 1 year, and leakage of cerebrospinal fluid between group A and group B (P < 0.05), but there was no significant difference in other variables between the two groups (P > 0.05). The preoperative average JOA score of group A was 6.37 and that of group B was 5.19. In group A, the average JOA score at 6 months, 1 year and 2 years after surgery was 7.87, 8.23 and 8.26, respectively, and the average JOA score improvement rate was 32.79 %, 38.32 and 38.53 %, respectively. In group B, the average JOA score at 6 months, 1 year and 2 years after surgery was 7.74, 8.15 and 8.29, respectively, and the average JOA score improvement rate was 39.15 %, 46.86 and 47.12 %, respectively.Conclusions: Currently, there is no consensus on whether instrumentation is needed after laminectomy for TOLF. We found that for patients with a long duration of gait disturbance, urination disorder, preoperative duration of symptoms, intramedullary signal change on MRI, dural ossification, residual rate of cross-sectional spinal canal area on CT less than 60 %, and shape on the sagittal MRI being beak and low, pre-mJOA had better clinical effects after LI as compared to those after LA, and the incidence of perioperative complications was lower. [ABSTRACT FROM AUTHOR]

Background: Recent studies suggest that lncRNAs may play significant roles in the development of hepatitis B virus (HBV) infection. However, as a special stage of HBV infection, the lncRNA expression in occult HBV infection (OBI) remains unclear. Methods: The plasma level of 15 HBV infection-related lncRNAs was initially detected using qRT-PCR in 10 OBI and 10 healthy controls (HCs) in discovery phase. Significantly dysregulated lncRNAs were subsequently validated in another 64 OBI, 20 HCs, 31 chronic hepatitis B (CHB) and 20 asymptomatic HBsAg carriers (ASC). Moreover, the AP000253 expression in liver tissues and its potential biological functions in HBV infection were further investigate with public transcriptomic data and HBV-expressing cell lines. Results: Among candidate lncRNAs, the plasma level of AP000253 decreased significantly in OBI, ASC and CHB patients compared to HCs, while no difference was found among OBI, ASC and CHB patients. In liver tissues, similar AP000253 expression was also observed from the GSE83148 dataset, while that in HBV-expressing hepatoma cells was opposite. ROC curve analysis indicated that plasma AP000253 yielded an AUC of 0.73 with 60% sensitivity and 75% specificity when differentiating OBI from HCs, but it could not specifically separate the stage of chronic HBV infection. Furthermore, functional experiments suggested that AP000253 could promote HBV transcription and replication in hepatoma cell lines. Conclusions: AP000253 might be involved in HBV replication, and be served as a potential biomarker for HBV infection. In the setting of blood donations, plasma AP000253 would be more useful to moderately distinguish OBI in HBsAg-negative donors. However, the AP000253 expression in liver tissues and associated molecular mechanism of HBV infection deserve further study in future. [ABSTRACT FROM AUTHOR]

Background: Presentation with massive systemic embolization as the initial manifestation of occult malignancy is infrequent. The standard management of cancer-related arterial thromboembolism has not yet been established.Case Presentation: We described a case of Trousseau's syndrome resulting in acute ischemic stroke concomitant with multiple embolizations in the spleen and kidney during oral administration of dabigatran for pulmonary embolism preceding the diagnosis of a malignant tumor. A cancer-related hypercoagulable state was suspected because the patient was admitted to the neurology department due to acute ischemic stroke with three territory infarcts on diffusion-weighted imaging (DWI) in the absence of identifiable conventional risk factors and brain vessel narrowing. The patient was subsequently diagnosed with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) (stage IV) with pleural metastasis. Administration of low-molecular-weight heparin followed by long-term dabigatran under effective cancer therapy comprising gefitinib and subsequent chemotherapy did not cause stroke relapse during the 1-year follow-up.Conclusions: This case suggests that cancer-related hypercoagulability should be considered an important etiology for stroke patients who develop unexplained disseminated acute cerebral infarction without conventional stroke risk factors, especially concomitant with multiple organ embolization. Novel oral anticoagulants may be an alternative therapy for the long-term management of cancer-related arterial thromboembolism under effective cancer therapy. [ABSTRACT FROM AUTHOR]

Background: The shift of oral microbiota is a critical factor of radiation caries in head and neck cancer patients after the radiotherapy. However, the direct effects of irradiation on the genome and virulence of cariogenic bacteria are poorly described. Here we investigated the genomic mutations and virulence change of Streptococcus mutans (S. mutans), the major cariogenic bacteria, exposed to the therapeutic doses of X-rays. Results: X-ray reduced the survival fraction of S. mutans and impacted its biofilm formation. We isolated a biofilm formation-deficient mutant #858 whose genome only possessed three synonymous mutations (c.2043 T > C, c.2100C > T, c.2109A > G) in gtfB gene. The "silent mutation" of c.2043 T > C in gtfB gene can cause the down-regulation of all of the gtfs genes' expression and decrease the GtfB enzyme secretion without the effect on the growth due to the codon bias. #858 and synonymous point mutation strain gtfB2043 T>C, similar to the gtfB gene null mutant Δ gtfB, can significantly decrease the extracellular polysaccharide production, biofilm formation and cariogenic capabilities both in vitro and in vivo compared with wild type. Conclusion: The direct exposure of X-ray radiation can affect the genome and virulence of oral bacteria even at therapeutic doses. The synonymous mutations of genome are negligent factors for gene expression and related protein translation due to the codon usage frequency. [ABSTRACT FROM AUTHOR]

Background: A considerable number of muscle development-related genes were differentially expressed in the early stage of avian adipocyte differentiation. However, the functions of them in adipocyte differentiation remain largely known. In this study, the myoblast determination protein 1 (MYOD1) was selected as a representative of muscle development. We investigated its expression, function, and regulation in avian adipocyte differentiation. Results: The expression of MYOD1 decreased significantly in the early stage of avian adipocyte differentiation. CRISPR/Cas9-mediated deletion of MYOD1 induced adipocyte differentiation, whereas over-expression of MYOD1 inhibited adipogenesis. The mRNA-seq data showed that MYOD1 could perturb the lipid biosynthetic process during differentiation. Our results showed that MYOD1 directly up-regulates the miR-206 expression by binding the upstream 1200 bp region of miR-206. Then, over-expression of miR-206 can inhibit the adipogenesis. Furthermore, MYOD1 affected the expression of endogenous miR-206 and its target gene Kruppel-like factor 4 (KLF4), which is an important activator of adipogenesis. Accordingly, the inhibition of miR-206 or over-expression of KLF4 could counteract the inhibitory effect of MYOD1 on adipocyte differentiation. Conclusions: Our results establish that MYOD1 inhibits adipocyte differentiation by up-regulating miR-206 to suppress the KLF4 expression. These findings identify a novel function of MYOD1 in adipocyte differentiation, suggesting a potential role in body-fat distribution regulation. [ABSTRACT FROM AUTHOR]

Background: To analyze the impact of spino cranial angle (SCA) on alteration of cervical alignment after multi-level anterior cervical discectomy fusion (ACDF) and explore the relationship between SCA and health-related quality of life (HRQOL) scores. Material and methods: In total, 49 patients following multi-level ACDF for multi-level cervical spondylotic myelopathy (MCSM) with more than 2 years follow-up period were enrolled. Radiographic data including SCA were measured. Receiver operating characteristics (ROC) curve analysis was applied to confirm the optimal cut-off values of SCA for predicting sagittal balance. Patients were divided into two groups on the basis of the cut-off value of preoperative SCA. Correlation coefficients were analyzed between SCA and HRQOL scores. Results: Optimal cut-off values for predicting sagittal balance was SCA of 88.6°. Patients with higher SCA, no matter preoperatively, postoperatively and at follow-up, got lower T1-Slope (T1s), C2–C7 lordosis angle (CA) and higher △SCA (pre vs post: p = 0.036, pre vs F/U: p = 0.022). Simultaneously, pre-SCA, post-SCA, and F/U-SCA in the high SCA group were positively correlated with the pre-NDI, post-NDI, and F/U-NDI scores respectively (pre: p < 0.001, post: p = 0.015, F/U: p = 0.003). However, no correlation was performed in the low SCA group. Conclusion: An excessive SCA can be considered to cause poorer clinical outcomes at preoperative and better correction after surgery. The SCA could be used as a new reference value to determine sagittal balance parameters of the cervical spine and to assess the quality of life. [ABSTRACT FROM AUTHOR]

Background: To study the impact of changes in spino-cranial angle (SCA) on sagittal alignment and to investigate the relationship between SCA and Neck Disability Index (NDI) scores after laminoplasty (LP) Material and methods: In total, 72 patients with multilevel cervical spondylotic myelopathy (MCSM) after laminoplasty (LP) were retrospectively enrolled. Based on the optimal cut-off values of preoperative SCA, patients were classified into low SCA and high SCA groups. Radiographic data were measured, including spino-cranial angle (SCA), T1-slope (T1s), C2–7 lordosis (CA), T1s minus CA (T1sCA), and C2–7 sagittal vertical axis (cSVA). JOA and NDI scores were both applied to assess postoperative and follow-up clinical efficacy. Pearson correlation coefficient and linear regression analysis were respectively calculated between radiographic data and between SCA and NDI. Results: The preoperative SCA was significantly correlated with T1s (r = − 0.795), CA (r = − 0.857), and cSVA (r = 0.915). A receiver operating characteristic (ROC) curve model predicted a threshold of SCA (value of 85.2°). At the follow-up period, patients with lower SCA had a higher T1s and CA and a lower cSVA, simultaneously accompanied by greater △T1s, △CA, and △cSVA. The linear regression model demonstrated that SCA in the higher group was positively correlated with NDI, and patients with higher SCA had worse NDI scores (pre: p < 0.001; post: p < 0.001; F/U: p = 0.003) and greater changes of NDI (post: p < 0.010; F/U: p = 0.002). Conclusion: SCA may be a good predictor of evaluating sagittal balance and planning surgery. Changes in sagittal alignment in the low SCA group were affected more easily, and a higher SCA was associated with worse quality of life. Laminoplasty could be a good choice for patients with lower SCA. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) possess multipotent properties that make them promising candidates for immunomodulation and regenerative medicine. However, MSC heterogeneity poses challenges to their research reproducibility and clinical application. The emergence of single-cell RNA sequencing (scRNA-seq) technology has enabled a thorough examination of MSC heterogeneity, underscoring the necessity for a specialized platform to systematically analyze the published datasets derived from MSC scRNA-seq experiments. However, large-scale integration and in-depth exploration of MSC scRNA-seq datasets to comprehensively depict their developmental patterns, relationships, and knowledge are still lacking. Here, we present MSCsDB (http://mscsdb.jflab.ac.cn:18088/index/), an interactive database that has been constructed using high-quality scRNA-seq datasets from all published sources on MSCs. MSCsDB provides a one-stop interactive query for regulon activities, gene ontology enrichment, signature gene visualization and transcription factor regulon analysis. Additionally, the dedicated module within MSCsDB was developed to facilitate the evaluation of MSC quality, thereby promoting the standardization of MSC subtype usage. Notably, MSCsDB enables users to analyze their MSCs scRNA-seq data directly, yielding visually appealing outputs of exceptional quality that can be conveniently downloaded via email. Furthermore, MSCsDB integrates the current comprehensive MSC atlas taxonomy, which includes 470,000 cells and 5 tissues from 26 subjects, as publicly available references. These references provide molecular characterization and phenotypic prediction for annotating MSC subsets. In summary, MSCsDB serves as a user-friendly and contemporary data repository for human MSCs, offering a dedicated platform that enables users to effectively conduct comprehensive analyses on their individual MSCs scRNA-seq data. [ABSTRACT FROM AUTHOR]

Background: Protein model quality assessment (QA) is an essential procedure in protein structure prediction. QA methods can predict the qualities of protein models and identify good models from decoys. Clustering-based methods need a certain number of models as input. However, if a pool of models are not available, methods that only need a single model as input are indispensable. Results: We developed MASS, a QA method to predict the global qualities of individual protein models using random forests and various novel energy functions. We designed six novel energy functions or statistical potentials that can capture the structural characteristics of a protein model, which can also be used in other protein-related bioinformatics research. MASS potentials demonstrated higher importance than the energy functions of RWplus, GOAP, DFIRE and Rosetta when the scores they generated are used as machine learning features. MASS outperforms almost all of the four CASP11 top-performing single-model methods for global quality assessment in terms of all of the four evaluation criteria officially used by CASP, which measure the abilities to assign relative and absolute scores, identify the best model from decoys, and distinguish between good and bad models. MASS has also achieved comparable performances with the leading QA methods in CASP12 and CASP13. Conclusions: MASS and the source code for all MASS potentials are publicly available at http://dna.cs.miami.edu/MASS/. [ABSTRACT FROM AUTHOR]

Background: Growing evidence has suggested that immune-related genes play crucial roles in the development and progression of hepatocellular carcinoma (HCC). Nevertheless, the utility of immune-related genes for evaluating the prognosis of HCC patients are still lacking. The study aimed to explore gene signatures and prognostic values of immune-related genes in HCC.Methods: We comprehensively integrated gene expression data acquired from 374 HCC and 50 normal tissues in The Cancer Genome Atlas (TCGA). Differentially expressed genes (DEGs) analysis and univariate Cox regression analysis were performed to identify DEGs that related to overall survival. An immune prognostic model was constructed using the Lasso and multivariate Cox regression analyses. Furthermore, Cox regression analysis was applied to identify independent prognostic factors in HCC. The correlation analysis between immune-related signature and immune cells infiltration were also investigated. Finally, the signature was validated in an external independent dataset.Results: A total of 329 differentially expressed immune-related genes were detected. 64 immune-related genes were identified to be markedly related to overall survival in HCC patients using univariate Cox regression analysis. Then we established a TF-mediated network for exploring the regulatory mechanisms of these genes. Lasso and multivariate Cox regression analyses were applied to construct the immune-based prognostic model, which consisted of nine immune-related genes. Further analysis indicated that this immune-related prognostic model could be an independent prognostic indicator after adjusting to other clinical factors. The relationships between the risk score model and immune cell infiltration suggested that the nine-gene signature could reflect the status of tumor immune microenvironment. The prognostic value of this nine-gene prognostic model was further successfully validated in an independent database.Conclusions: Together, our study screened potential prognostic immune-related genes and established a novel immune-based prognostic model of HCC, which not only provides new potential prognostic biomarkers and therapeutic targets, but also deepens our understanding of tumor immune microenvironment status and lays a theoretical foundation for immunotherapy. [ABSTRACT FROM AUTHOR]

Background: The genome architecture mapping (GAM) technique can capture genome-wide chromatin interactions. However, besides the known systematic biases in the raw GAM data, we have found a new type of systematic bias. It is necessary to develop and evaluate effective normalization methods to remove all systematic biases in the raw GAM data. Results: We have detected a new type of systematic bias, the fragment length bias, in the genome architecture mapping (GAM) data, which is significantly different from the bias of window detection frequency previously mentioned in the paper introducing the GAM method but is similar to the bias of distances between restriction sites existing in raw Hi-C data. We have found that the normalization method (a normalized variant of the linkage disequilibrium) used in the GAM paper is not able to effectively eliminate the new fragment length bias at 1 Mb resolution (slightly better at 30 kb resolution). We have developed an R package named normGAM for eliminating the new fragment length bias together with the other three biases existing in raw GAM data, which are the biases related to window detection frequency, mappability, and GC content. Five normalization methods have been implemented and included in the R package including Knight-Ruiz 2-norm (KR2, newly designed by us), normalized linkage disequilibrium (NLD), vanilla coverage (VC), sequential component normalization (SCN), and iterative correction and eigenvector decomposition (ICE). Conclusions: Based on our evaluations, the five normalization methods can eliminate the four biases existing in raw GAM data, with VC and KR2 performing better than the others. We have observed that the KR2-normalized GAM data have a higher correlation with the KR-normalized Hi-C data on the same cell samples indicating that the KR-related methods are better than the others for keeping the consistency between the GAM and Hi-C experiments. Compared with the raw GAM data, the normalized GAM data are more consistent with the normalized distances from the fluorescence in situ hybridization (FISH) experiments. The source code of normGAM can be freely downloaded from http://dna.cs.miami.edu/normGAM/. [ABSTRACT FROM AUTHOR]

This study aimed to identify new pyroptosis-associated tumor antigens for use in mRNA vaccines and the screening of sensitive LUAD populations suitable for vaccination. The association between tumor immune infiltrating cell abundance and potential tumor antigens was investigated and visualized using the analysis modules of gene expression, clinical outcomes, and somatic copy number variation. In addition, the pyroptosis-related genes (PRGs) were clustered, the relative pyroptosis subtypes (PSs) and gene modules were identified, and the prognostic value of the PSs was examined. The expression of key PRGs in two lung adenocarcinoma cell lines was verified by RT-qPCR. Four tumor pyroptosis-associated antigens, CARD8, NAIP, NLRP1, and NLRP3, were screened as potential candidates for LUAD mRNA vaccine development. In the construction of consensus clusters for PRGs, two PSs, PS1 and PS2, were classified, in which patients with PS1 LUAD had a better prognosis. In contrast, patients with PS2 LUAD may have better responsiveness to mRNA vaccine treatment. The key PRGs can be regarded as biomarkers to predict the LUAD prognosis and identify patients suitable for mRNA vaccines. The RT-qPCR results showed that the expression levels of CSMD3, LRP1B, MUC16 and TTN were significantly increased in the two lung adenocarcinoma cell lines, while the expression levels of CARD8, TP53 and ZFHX4 were significantly reduced. The antigens CARD8, NAIP, NLRP1, and NLRP3, which are associated with tumor pyroptosis, could be candidate molecules for LUAD mRNA vaccine development. Patients with PS2 LUAD may be suitable candidates for mRNA vaccine treatment. [ABSTRACT FROM AUTHOR]

Background: Hi-C data have been widely used to reconstruct chromosomal three-dimensional (3D) structures. One of the key limitations of Hi-C is the unclear relationship between spatial distance and the number of Hi-C contacts. Many methods used a fixed parameter when converting the number of Hi-C contacts to wish distances. However, a single parameter cannot properly explain the relationship between wish distances and genomic distances or the locations of topologically associating domains (TADs). Results: We have addressed one of the key issues of using Hi-C data, that is, the unclear relationship between spatial distances and the number of Hi-C contacts, which is crucial to understand significant biological functions, such as the enhancer-promoter interactions. Specifically, we developed a new method to infer this converting parameter and pairwise Euclidean distances based on the topology of the Hi-C complex network (HiCNet). The inferred distances were modeled by clustering coefficient and multiple other types of constraints. We found that our inferred distances between bead-pairs within the same TAD were apparently smaller than those distances between bead-pairs from different TADs. Our inferred distances had a higher correlation with fluorescence in situ hybridization (FISH) data, fitted the localization patterns of Xist transcripts on DNA, and better matched 156 pairs of protein-enabled long-range chromatin interactions detected by ChIA-PET. Using the inferred distances and another round of optimization, we further reconstructed 40 kb high-resolution 3D chromosomal structures of mouse male ES cells. The high-resolution structures successfully illustrate TADs and DNA loops (peaks in Hi-C contact heatmaps) that usually indicate enhancer-promoter interactions. Conclusions: We developed a novel method to infer the wish distances between DNA bead-pairs from Hi-C contacts. High-resolution 3D structures of chromosomes were built based on the newly-inferred wish distances. This whole process has been implemented as a tool named HiCNet, which is publicly available at http://dna.cs.miami.edu/HiCNet/. [ABSTRACT FROM AUTHOR]

Following publication of the original article [1], the authors reported that Table 1 contained some errors in the GenBank number of BT gene. The correct Table 1 is presented below. [ABSTRACT FROM AUTHOR]

Background: The current treatments for adjacent two-segment cervical spondylotic myelopathy (CSM) include two-segment anterior cervical discectomy and fusion (ACDF) and single-segment anterior cervical corpectomy and fusion (ACCF). Long-term follow-up has demonstrated that both procedures have complications such as reduced cervical mobility, accelerated degeneration of adjacent segments and loosening of internal fixation screws. The purpose of this study is to demonstrate the feasibility, safety, and efficacy of anterior percutaneous full-endoscopic transcorporeal decompression of the spinal cord (APFETDSC) via one vertebra with two bony channels for the treatment of adjacent two-segment CSM and to present our surgical experience. Methods: Anterior percutaneous full-endoscopic transcorporeal decompression of the spinal cord (APFETDSC) via one vertebra with two bony channels was performed for 12 patients with adjacent two-segment CSM with follow-up care for at least 12 months. The Visual analog scale (VAS) and the Japanese Orthopedic Association Score (JOA) were recorded, and modified Macnab criteria were used to evaluate the treatment excellence rate. Radiological examinations, including X-ray, computed tomography (CT) and magnetic resonance imaging (MRI), were used to evaluate spinal cord decompression, intervertebral stability and healing of the bony channel. Results: All 12 patients completed the operation successfully. No postoperative complications, such as dysphagia, Horner's syndrome, or laryngeal recurrent nerve palsy, were found. The postoperative VAS and JOA scores were significantly improved compared with those before surgery(P < 0.001). According to the modified Macnab criteria, the clinical outcome was excellent in 8 cases, good in 3 cases and fine in 1 case at the final follow-up and the excellent and good rate was 91.7%. Postoperative and follow-up imaging showed significant spinal cord decompression, well-healed bony channels and no cervical instability. Conclusions: This study is the first report of anterior percutaneous full-endoscopic transcorporeal decompression of the spinal cord via one vertebra with two bony channels. This procedure has the advantages of less trauma, faster recovery, fewer complications and no need to implant internal fixators. This is a minimally invasive, feasible and safe surgical procedure for patients with adjacent two-segment CSM. [ABSTRACT FROM AUTHOR]

Background: Progressive supranuclear palsy (PSP) with a frontal presentation, characterized by cognitive deficits and behavioral changes, has been recognized as an early clinical picture, distinct from the classical so-called Richardson and parkinsonism presentations. The midcingulate cortex is associated with executive and attention tasks and has consistently been found to be impaired in imaging studies of patients with PSP. The aim of the present study was to determine alterations in neurotransmission underlying the pathophysiology of PSP, as well as their significance for clinically identifiable PSP subgroups. Methods: In vitro receptor autoradiography was used to quantify densities of 20 different receptors in the caudate nucleus and midcingulate area 24' of patients with PSP (n = 16) and age- and sex-matched control subjects (n = 14). Results: Densities of γ-aminobutyric acid type B, peripheral benzodiazepine, serotonin receptor type 2, and N-methyl-d-aspartate receptors were significantly higher in area 24′ of patients with PSP, where tau impairment was stronger than in the caudate nucleus. Kainate and nicotinic cholinergic receptor densities were significantly lower, and adenosine receptor type 1 (A1) receptors significantly higher, in the caudate nucleus of patients with PSP. Receptor fingerprints also segregated PSP subgroups when clinical parameters such as occurrence of frontal presentation and tau pathology severity were taken into consideration. Conclusions: We demonstrate, for the first time to our knowledge, that kainate and A1 receptors are altered in PSP and that clinically identifiable PSP subgroups differ at the neurochemical level. Numerous receptors were altered in the midcingulate cortex, further suggesting that it may prove to be a key region in PSP. Finally, we add to the evidence that nondopaminergic systems play a role in the pathophysiology of PSP, thus highlighting potential novel treatment strategies. [ABSTRACT FROM AUTHOR]

Background: α-synuclein (α-syn) is the main component of intracytoplasmic inclusions deposited in the brains of patients with Parkinson's disease (PD) and certain other neurodegenerative disorders. Recent studies have explored the ability of α-syn to propagate between or across neighboring neurons and supposedly "infect" them with a prion-like mechanism. However, much of this research has used stereotaxic injections of heterologous α-syn fibrils to induce the spreading of inclusions in the rodent brains. Whether α-syn is able to transmit from the host cells to their neighboring cells in vivo is unclear. Methods: Using immunestaining, we examined the potential propagation of α-syn into nigrostriatal dopaminergic (DA) neurons in three lines of transgenic mice that overexpress human wild-type α-syn (hα-syn) in different neuron populations. Results: After testing for three different routes by which hα-syn propagation might occur, we were unable to find any evidence that hα-syn behaved like a prion and could be transmitted overtime into the DA neurons initially lack of hα-syn expression. Conclusions: In transgenic mice hα-syn does not have the ability to propagate at pathologically significant levels between or across neurons. It must be noted that these observations do not disprove the studies that show its prion-like qualities, but rather that propagation is not detectable in transgenic models that do not use any injections of heterologous proteins or viral vectors to induce a spreading state. [ABSTRACT FROM AUTHOR]

Background: This study aimed to develop an integrated model for predicting the occurrence of postoperative seizures in patients with diffuse high-grade gliomas (DHGGs) using clinical and RNA-seq data. Methods: Patients with DHGGs, who received prophylactic anti-epileptic drugs (AEDs) for three months following surgery, were enrolled into the study. The patients were assigned randomly into training (n = 166) and validation (n = 42) cohorts. Differentially expressed genes (DEGs) were identified based on preoperative glioma-related epilepsy (GRE) history. Least absolute shrinkage and selection operator (LASSO) logistic regression analysis was used to construct a predictive gene-signature for the occurrence of postoperative seizures. The final integrated prediction model was generated using the gene-signature and clinical data. Receiver operating characteristic analysis and calibration curve method were used to evaluate the accuracy of the gene-signature and prediction model using the training and validation cohorts. Results: A seven-gene signature for predicting the occurrence of postoperative seizures was developed using LASSO logistic regression analysis of 623 DEGs. The gene-signature showed satisfactory predictive capacity in the training cohort [area under the curve (AUC) = 0.842] and validation cohort (AUC = 0.751). The final integrated prediction model included age, temporal lobe involvement, preoperative GRE history, and gene-signature-derived risk score. The AUCs of the integrated prediction model were 0.878 and 0.845 for the training and validation cohorts, respectively. Conclusion: We developed an integrated prediction model for the occurrence of postoperative seizures in patients with DHGG using clinical and RNA-Seq data. The findings of this study may contribute to the development of personalized management strategies for patients with DHGGs and improve our understanding of the mechanisms underlying GRE in these patients. [ABSTRACT FROM AUTHOR]

Objectives: To identify age-related radiographic risk factors for degenerative lumbar spinal stenosis (DLSS) and analyze correlations among them. Methods: A total of 180 cases were enrolled in this study, and lumbar magnetic resonance was performed. Among them, 93 cases suffered DLSS and lumbar dynamic X-ray was examined. And following parameters were measured and evaluated: intervertebral disk height (IDH), the ratio of IDH(IDHL4-5/L3-4), initial IDH of L4-5(iIDHL4-5) in the DLSS group, disk degeneration (DD), cartilaginous endplate failure (CEF), Modic changes, the thickness of ligamentum flavum (LF), range of intervertebral motion (ROM), facet joint opening (FJO), facet joint angle (FJA), the standard cross-sectional area (SCSA) of the multifidus, erector spinae, and psoas major muscles. The data of two groups were compared, and the possible risk factors of DLSS were analyzed. Results: Compared with the control group, the DLSS group had higher IDH except for L4-5 and larger iIDHL4-5 (P < 0.05). Significant differences were shown in CEF and the thickness of LF at L1-S1 and DD at L4-5 (P < 0.05). The DLSS group had smaller SCSA of multifidus, erector spinae, and psoas major muscles but greater FJA, FJO (P < 0.05). And the risk of DLSS increased when iIDHL4-5 ≥ 10.73 mm, FJA ≥ 52.03° , or FJO ≥ 3.75 mm. IDH positively correlated with SCSA of multifidus and psoas major muscles and ROM at L1-S1 (P < 0.05). DD showed negative linear relations with SCSA of multifidus and psoas muscle and positive linear relation with CEF at L1-2, L2-3, and L5-S1 (P < 0.05). Conclusion: Larger initial disk height and excessive CEF may induce DLSS by increasing intervertebral mobility to promote DD, and atrophied paravertebral muscles by weakening the stability of lumbar spine. [ABSTRACT FROM AUTHOR]

Background: The subjective sign of a serious pandemic in human work and life is mathematical neural tinnitus. fNIRS (functional near-infrared spectroscopy) is a new non-invasive brain imaging technology for studying the neurological activity of the human cerebral cortex. It is based on neural coupling effects. This research uses the fNIRS approach to detect differences in the neurological activity of the cerebral skin in the sound stimulation mission in order to better discriminate between the sensational neurological tinnitus. Methods: In the fNIRS brain imaging method, 14 sensorineural tinnitus sufferers and 14 healthy controls listened to varied noise and quiet for fNIRS data collection. Linear fitting was employed in MATLAB to eliminate slow drifts during preprocessing and event-related design analysis. The false discovery rate (FDR) procedure was applied in IBM SPSS Statistics 26.0 to control the false positive rate in multiple comparison analyses. Results: When the ill group and the healthy control group were stimulated by pink noise, there was a significant difference in blood oxygen concentration (P < 0.05), and the healthy control group exhibited a high activation, according to the fNIRS measurement data. The blood oxygen concentration level in the patient group was dramatically enhanced after one month of acupuncture therapy under the identical stimulation task settings, and it was favorably connected with the levels of THI and TEQ scales. Conclusions: Using sensorineural tinnitus illness as an example, fNIRS technology has the potential to disclose future pathological study on subjective diseases throughout time. Other clinical disorders involving the temporal lobe and adjacent brain areas may also be examined, in addition to tinnitus-related brain alterations. [ABSTRACT FROM AUTHOR]

Background: The subjective sign of a serious pandemic in human work and life is mathematical neural tinnitus. fNIRS (functional near-infrared spectroscopy) is a new non-invasive brain imaging technology for studying the neurological activity of the human cerebral cortex. It is based on neural coupling effects. This research uses the fNIRS approach to detect differences in the neurological activity of the cerebral skin in the sound stimulation mission in order to better discriminate between the sensational neurological tinnitus. Methods: In the fNIRS brain imaging method, 14 sensorineural tinnitus sufferers and 14 healthy controls listened to varied noise and quiet for fNIRS data collection. Linear fitting was employed in MATLAB to eliminate slow drifts during preprocessing and event-related design analysis. The false discovery rate (FDR) procedure was applied in IBM SPSS Statistics 26.0 to control the false positive rate in multiple comparison analyses. Results: When the ill group and the healthy control group were stimulated by pink noise, there was a significant difference in blood oxygen concentration (P < 0.05), and the healthy control group exhibited a high activation, according to the fNIRS measurement data. The blood oxygen concentration level in the patient group was dramatically enhanced after one month of acupuncture therapy under the identical stimulation task settings, and it was favorably connected with the levels of THI and TEQ scales. Conclusions: Using sensorineural tinnitus illness as an example, fNIRS technology has the potential to disclose future pathological study on subjective diseases throughout time. Other clinical disorders involving the temporal lobe and adjacent brain areas may also be examined, in addition to tinnitus-related brain alterations. [ABSTRACT FROM AUTHOR]

Predicting protein function from sequence is useful for biochemical experiment design, mutagenesis analysis, protein engineering, protein design, biological pathway analysis, drug design, disease diagnosis, and genome annotation as a vast number of protein sequences with unknown function are routinely being generated by DNA, RNA and protein sequencing in the genomic era. However, despite significant progresses in the last several years, the accuracy of protein function prediction still needs to be improved in order to be used effectively in practice, particularly when little or no homology exists between a target protein and proteins with annotated function. Here, we developed a method that integrated profile-sequence alignment, profile-profile alignment, and Domain Co-Occurrence Networks (DCN) to predict protein function at different levels of complexity, ranging from obvious homology, to remote homology, to no homology. We tested the method blindingly in the 2011 Critical Assessment of Function Annotation (CAFA). Our experiments demonstrated that our three-level prediction method effectively increased the recall of function prediction while maintaining a reasonable precision. Particularly, our method can predict function terms defined by the Gene Ontology more accurately than three standard baseline methods in most situations, handle multi-domain proteins naturally, and make ab initio function prediction when no homology exists. These results show that our approach can combine complementary strengths of most widely used BLAST-based function prediction methods, rarely used in function prediction but more sensitive profile-profile comparison-based homology detection methods, and non-homology-based domain co-occurrence networks, to effectively extend the power of function prediction from high homology, to low homology, to no homology (ab initio cases). [ABSTRACT FROM AUTHOR]

Background: The Warburg effect is a hallmark characteristic of colorectal cancer (CRC). Despite extensive research, the role of long non-coding RNAs (lncRNAs) in influencing the Warburg effect remains incompletely understood. Our study aims to identify lncRNAs that may modulate the Warburg effect by functioning as competing endogenous RNAs (ceRNAs). Methods: Utilizing bioinformatics approaches, we extracted glycolysis-associated gene data from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and identified 101 glycolysis-related lncRNAs in CRC. We employed Univariable Cox regression, Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, and Multivariable Cox regression to develop a prognostic model comprising four glycolysis-linked lncRNAs. We then constructed a prognostic nomogram integrating this lncRNA model with other relevant clinical parameters. Results: The prognostic efficacy of our four-lncRNA signature and its associated nomogram was validated in both training and validation cohorts. Functional assays demonstrated significant glycolysis and hexokinase II (HK2) inhibition following the silencing of RUNDC3A − AS1, a key lncRNA in our prognostic signature, highlighting its regulatory importance in the Warburg effect. Conclusions: Our research illuminates the critical role of glycolysis-centric lncRNAs in CRC. The developed prognostic model and nomogram underscore the pivotal prognostic and regulatory significance of the lncRNA RUNDC3A − AS1 in the Warburg effect in colorectal cancer. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to compare cervical sagittal parameters and clinical outcomes between patients undergoing cervical laminoplasty(CL) and those undergoing lateral mass screw fixation(LMS). Methods: We retrospectively studied 67 patients with multilevel ossification of the posterior longitudinal ligament (OPLL) of the cervical spine who underwent lateral mass screw fixation (LMS = 36) and cervical laminoplasty (CL = 31). We analyzed cervical sagittal parameters (C2-7 sagittal vertical axis (C2-7 SVA), C0-2 Cobb angle, C2-7 Cobb angle, C7 slope (C7s), T1 slope (T1s), and spino-cranial angle (SCA)) and clinical outcomes (visual analog scale [VAS], neck disability index [NDI], Japanese Orthopaedic Association [JOA] scores, recovery rate (RR), and minimum clinically significant difference [MCID]). The cervical sagittal parameters at the last follow-up were analyzed by binary logistic regression. Finally, we analyzed the correlation between the cervical sagittal parameters and each clinical outcome at the last follow-up after surgery in both groups. Results: At the follow-up after posterior decompression in both groups, the mean values of C2-C7 SVA, C7s, and T1s in the LMS group were more significant than those in the CL group (P ≤ 0.05). Compared with the preoperative period, C2-C7 SVA, T1s, and SCA gradually increased, and the C2-C7 Cobb angle gradually decreased after surgery (P < 0.05). The improvement in the JOA score and the recovery rate was similar between the two groups, while the improvement in the VAS-N score and NDI score was more significant in the CL group (P = 0.001; P = 0.043). More patients reached MCID in the CL group than in the LMS group (P = 0.036). Binary logistic regression analysis showed that SCA was independently associated with whether patients reached MCID at NDI postoperatively. SCA was positively correlated with cervical NDI and negatively correlated with cervical JOA score at postoperative follow-up in both groups (P < 0.05); C2-7 Cobb angle was negatively correlated with cervical JOA score at postoperative follow-up (P < 0.05). Conclusion: CL may be superior to LMS in treating cervical spondylotic myelopathy caused by OPLL. In addition, smaller cervical SCA after posterior decompression may suggest better postoperative outcomes. [ABSTRACT FROM AUTHOR]

Background: Bone marrow mesenchymal stem cells (BMSCs) can undergo inadequate osteogenesis or excessive adipogenesis as they age due to changes in the bone microenvironment, ultimately resulting in decreased bone density and elevated risk of fractures in senile osteoporosis. This study aims to investigate the effects of osteocyte senescence on the bone microenvironment and its influence on BMSCs during aging. Results: Primary osteocytes were isolated from 2-month-old and 16-month-old mice to obtain young osteocyte-derived extracellular vesicles (YO-EVs) and senescent osteocyte-derived EVs (SO-EVs), respectively. YO-EVs were found to significantly increase alkaline phosphatase activity, mineralization deposition, and the expression of osteogenesis-related genes in BMSCs, while SO-EVs promoted BMSC adipogenesis. Neither YO-EVs nor SO-EVs exerted an effect on the osteoclastogenesis of primary macrophages/monocytes. Our constructed transgenic mice, designed to trace osteocyte-derived EV distribution, revealed abundant osteocyte-derived EVs embedded in the bone matrix. Moreover, mature osteoclasts were found to release osteocyte-derived EVs from bone slices, playing a pivotal role in regulating the functions of the surrounding culture medium. Following intravenous injection into young and elderly mouse models, YO-EVs demonstrated a significant enhancement of bone mass and biomechanical strength compared to SO-EVs. Immunostaining of bone sections revealed that YO-EV treatment augmented the number of osteoblasts on the bone surface, while SO-EV treatment promoted adipocyte formation in the bone marrow. Proteomics analysis of YO-EVs and SO-EVs showed that tropomyosin-1 (TPM1) was enriched in YO-EVs, which increased the matrix stiffness of BMSCs, consequently promoting osteogenesis. Specifically, the siRNA-mediated depletion of Tpm1 eliminated pro-osteogenic activity of YO-EVs both in vitro and in vivo. Conclusions: Our findings suggested that YO-EVs played a crucial role in maintaining the balance between bone resorption and formation, and their pro-osteogenic activity declining with aging. Therefore, YO-EVs and the delivered TPM1 hold potential as therapeutic targets for senile osteoporosis. [ABSTRACT FROM AUTHOR]

Background: Gut dysbiosis has been linked with both HIV infection and diabetes, but its interplay with metabolic and inflammatory responses in diabetes, particularly in the context of HIV infection, remains unclear. Methods: We first conducted a cross-sectional association analysis to characterize the gut microbial, circulating metabolite, and immune/inflammatory protein features associated with diabetes in up to 493 women (~ 146 with prevalent diabetes with 69.9% HIV +) of the Women's Interagency HIV Study. Prospective analyses were then conducted to determine associations of identified metabolites with incident diabetes over 12 years of follow-up in 694 participants (391 women from WIHS and 303 men from the Multicenter AIDS Cohort Study; 166 incident cases were recorded) with and without HIV infection. Mediation analyses were conducted to explore whether gut bacteria–diabetes associations are explained by altered metabolites and proteins. Results: Seven gut bacterial genera were identified to be associated with diabetes (FDR-q < 0.1), with positive associations for Shigella, Escherichia, Megasphaera, and Lactobacillus, and inverse associations for Adlercreutzia, Ruminococcus, and Intestinibacter. Importantly, the associations of most species, especially Adlercreutzia and Ruminococcus, were largely independent of antidiabetic medications use. Meanwhile, 18 proteins and 76 metabolites, including 3 microbially derived metabolites (trimethylamine N-oxide, phenylacetylglutamine (PAGln), imidazolepropionic acid (IMP)), 50 lipids (e.g., diradylglycerols (DGs) and triradylglycerols (TGs)) and 23 non-lipid metabolites, were associated with diabetes (FDR-q < 0.1), with the majority showing positive associations and more than half of them (59/76) associated with incident diabetes. In mediation analyses, several proteins, especially interleukin-18 receptor 1 and osteoprotegerin, IMP and PAGln partially mediate the observed bacterial genera–diabetes associations, particularly for those of Adlercreutzia and Escherichia. Many diabetes-associated metabolites and proteins were altered in HIV, but no effect modification on their associations with diabetes was observed by HIV. Conclusion: Among individuals with and without HIV, multiple gut bacterial genera, blood metabolites, and proinflammatory proteins were associated with diabetes. The observed mediated effects by metabolites and proteins in genera–diabetes associations highlighted the potential involvement of inflammatory and metabolic perturbations in the link between gut dysbiosis and diabetes in the context of HIV infection. [ABSTRACT FROM AUTHOR]

Periodontitis is an inflammatory disease induced by the complex interactions between the host immune system and the microbiota of dental plaque. Oxidative stress and the inflammatory microenvironment resulting from periodontitis are among the primary factors contributing to the progression of the disease. Additionally, the presence of dental plaque microbiota plays a significant role in affecting the condition. Consequently, treatment strategies for periodontitis should be multi-faceted. In this study, a reactive oxygen species (ROS)-responsive drug delivery system was developed by structurally modifying hyaluronic acid (HA) with phenylboronic acid pinacol ester (PBAP). Curcumin (CUR) was encapsulated in this drug delivery system to form curcumin-loaded nanoparticles (HA@CUR NPs). The release results indicate that CUR can be rapidly released in a ROS environment to reach the concentration required for treatment. In terms of uptake, HA can effectively enhance cellular uptake of NPs because it specifically recognizes CD44 expressed by normal cells. Moreover, HA@CUR NPs not only retained the antimicrobial efficacy of CUR, but also exhibited more pronounced anti-inflammatory and anti-oxidative stress functions both in vivo and in vitro. This provides a good potential drug delivery system for the treatment of periodontitis, and could offer valuable insights for dental therapeutics targeting periodontal diseases. [ABSTRACT FROM AUTHOR]

The combination of immune checkpoint inhibitors and immunogenic cell death (ICD) inducers has become a promising strategy for the treatment of various cancers. However, its efficacy remains unmet because of the dense stroma and defective vasculatures in the tumor microenvironment (TME) that restricts the intratumoral infiltration of cytotoxic T lymphocytes (CTLs). Herein, cancer-associated fibroblasts (CAFs)-targeted nanoemulsions are tailored to combine the ICD induction and the TME reprogramming to sensitize checkpoint blockade immunotherapy. Melittin, as an ICD inducer and an antifibrotic agent, is efficiently encapsulated into the nanoemulsion accompanied by a nitric oxide donor to improve its bioavailability and tumor targeting. The nanoemulsions exhibited dual functionality by directly inducing direct cancer cell death and enhancing the tumoral immunogenicity, while also synergistically reprogramming the TME through reversing the activated CAFs, decreasing collagen deposition and restoring tumor vessels. Consequently, these nanemulsions successfully facilitated the CTLs infiltration and suppressing the recruitment of immunosuppressive cells. A combination of AE-MGNPs and anti-CTLA-4 antibody greatly elicited a striking level of antitumor T-cell response to suppress tumor growth in CAFs-rich colorectal tumor models. Our work emphasized the integration of the ICD induction with simultaneous modulation of the TME to enhance the sensitivity of patients to checkpoint blockade immunotherapy. Highlights: A synergistic therapy was developed by co-delivery of melittin and GSNO (AE-MGNPs) to amplify immunotherapy via remodeling tumor immunosuppressive microenvironment. AE-MGNPs reprogrammed the activated CAFs, normalized the tumor vessels and induced immunogenic cell death to improve the CTLs infiltration while suppressing the recruitment of immunosuppressive cells. A combination of AE-MGNPs and anti-CTLA-4 antibody greatly elicited a striking level of antitumor T-cell response to suppress tumor growth in CAFs-rich colorectal tumor models. [ABSTRACT FROM AUTHOR]

Objectives: Brasenia is a monotypic genus in the family of Cabombaceae. The only species, B. schreberi, is a macrophyte distributed worldwide. Because it requires good water quality, it is endangered in China and other countries due to the deterioration of aquatic habitats. The young leaves and stems of B. schreberi are covered by thick mucilage, which has high medical value. As an allelopathic aquatic plant, it can also be used in the management of aquatic weeds. Here, we present its assembled and annotated genome to help shed light on medial and allelopathic substrates and facilitate their conservation. Data description: Genomic DNA and RNA extracted from B. schreberi leaf tissues were used for whole genome and RNA sequencing using a Nanopore and/or MGI sequencer. The assembly was 1,055,148,839 bp in length, with 92 contigs and an N50 of 22,379,495 bp. The repetitive elements in the assembly were 555,442,205 bp. A completeness assessment of the assembly with BUSCO and compleasm indicated 88.4 and 90.9% completeness in the Eudicots database and 95.4 and 96.6% completeness in the Embryphyta database. Gene annotation revealed 67,747 genes that coded for 73,344 proteins. [ABSTRACT FROM AUTHOR]

Background: Firmiana danxiaensis is a critically endangered and ecologically important tree currently only found in four locations in Danxia or Karst habitats in northern Guangdong Province, China. The specialized habitat preference makes it an ideal model species for study of adaptive evolution. Meanwhile, the phylogenetic relationships of F. danxiaensis in four locations under two landforms are unclear. Therefore, we sequenced its complete chloroplast (cp.) genomes and conducted comprehensive interspecific and intrageneric plastome studies. Results: The F. danxiaensis plastomes in four locations showed a typical quadripartite and circular structure that ranged from 160,832 to 161,206 bp in size, with 112 unique genes encoded. Comparative genomics showed that the plastomes of F. danxiaensis were relatively conserved with high similarity of genome organization, gene number, GC content and SSRs. While the genomes revealed higher biased codon preferences in Karst habitat than those in Danxia habitats. Eighteen and 11 divergent hotpots were identified at interspecific and intrageneric levels for species identification and further phylogenetic studies. Seven genes (clpP, accD, ccsA, ndhH, rpl20, rpoC2, and rps4) were under positive selection and may be related to adaptation. Phylogenetic analysis revealed that F. danxiaensis is sister to F. major and F. simplex. However, the interspecific relationships are not consistent with the habitat types. Conclusions: The characteristics and interspecific relationship of F. danxiaensis plastomes provide new insights into further integration of geographical factors, environmental factors, and genetic variations on the genomic study of F. danxiaensis. Together, our study will contribute to the study of species identification, population genetics, and conservation biology of F. danxiaensis. [ABSTRACT FROM AUTHOR]