DeepBAM: a high-accuracy single-molecule CpG methylation detection tool for Oxford nanopore sequencing.

Recent nanopore sequencing system (R10.4) has enhanced base calling accuracy and is being increasingly utilized for detecting CpG methylation state. However, the robustness and universality of the methylation calling model in officially supplied Dorado remains poorly tested. In this study, we obtained heterogeneous datasets from human and plant sources to carry out comprehensive evaluations, which showed that Dorado performed significantly different across datasets. We therefore developed deep neural networks and implemented several optimizations in training a new model called DeepBAM. DeepBAM achieved superior and more stable performances compared with Dorado, including higher area under the ROC curves (98.47% on average and up to 7.36% improvement) and F1 scores (94.97% on average and up to 16.24% improvement) across the datasets. DeepBAM-based whole genome methylation frequencies have achieved >0.95 correlations with BS-seq on four of five datasets, outperforming Dorado in all instances. It enables unraveling allele-specific methylation patterns, including regions of transposable elements. The enhanced performance of DeepBAM paves the way for broader applications of nanopore sequencing in CpG methylation studies.

RUNX1 targeting AKT3 promotes alveolar hypercoagulation and fibrinolytic inhibition in LPS induced ARDS.

BACKGROUND: Alveolar hypercoagulation and fibrinolytic inhibition are mainly responsible for massive alveolar fibrin deposition, which are closely related with refractory hypoxemia in acute respiratory distress syndrome (ARDS). Our previous study testified runt-related transcription factor (RUNX1) participated in the regulation of this pathophysiology in this syndrome, but the mechanism is unknown. We speculate that screening the downstream genes associated with RUNX1 will presumably help uncover the mechanism of RUNX1. METHODS: Genes associated with RUNX1 were screened by CHIP-seq, among which the target gene was verified by Dual Luciferase experiment. Then the efficacy of the target gene on alveolar hypercoagulation and fibrinolytic inhibition in LPS-induced ARDS was explored in vivo as well as in vitro. Finally, whether the regulatory effects of RUNX1 on alveolar hypercoagulation and fibrinolytic in ARDS would be related with the screened target gene was also sufficiently explored. RESULTS: Among these screened genes, AKT3 was verified to be the direct target gene of RUNX1. Results showed that AKT3 was highly expressed either in lung tissues of LPS-induced rat ARDS or in LPS-treated alveolar epithelia cell type II (AECII). Tissue factor (TF) and plasminogen activator inhibitor 1 (PAI-1) were increasingly expressed both in lung tissues of ARDS and in LPS-induced AECII, which were all significantly attenuated by down-regulation of AKT3. Inhibition of AKT3 gene obviously ameliorated the LPS-induced lung injury as well as the collagen I expression in ARDS. RUNX1 overexpression not only promoted the expressions of TF, PAI-1, but also boosted AKT3 expression in vitro. More importantly, the efficacy of RUNX1 on TF, PAI-1 were all effectively reversed by down-regulation of AKT3 gene. CONCLUSION: AKT3 is an important target gene of RUNX1, through which RUNX1 exerted its regulatory role on alveolar hypercoagulation and fibrinolytic inhibition in LPS-induced ARDS. RUNX1/ATK3 signaling axis is expected to be a new target for the exploration of ARDS genesis and treatment.

Photocatalyst Au@Ni-MOFs with Different Plasmonic Coverages for Improved Hydrogen Evolution from Water.

Plasmonic materials are fundamental photosensitizer materials for photocatalytic reactions. Various structures, including core-shell types, satellite types, and distribution types, have been designed and prepared for the optimization of photocatalytic reactions. However, understanding the profound enhancement mechanism of various structures is still challenging. Thus, the plasmonic coverage is considered to be an index for analyzing the influence mechanism. Here, Au@Ni-MOF core-shell flower sphere-like photocatalysts are prepared, and the size of the flower sphere can be precisely regulated by varying the amount of Au. Thus, different plasmonic coverages are realized through the tuning of spheres of different sizes. The high plasmonic coverage of catalysts can enhance visible light absorption, facilitate the generation of photogenerated electron-hole pairs, and shorten the photogenerated carrier transport distance. Moreover, the exponential relationship between the photocatalytic hydrogen production performance and the plasmonic coverage can also be used as a guide for material design. As a result, a photocatalytic hydrogen production rate of 3389 µmol·g-1·h-1 is achieved in the Au@Ni-MOF sample with high plasmonic coverage, which will advance the plasmonic application in photocatalytic reactions.

Digital Surface-Enhanced Raman Spectroscopy-Lateral Flow Test Dipstick: Ultrasensitive, Rapid Virus Quantification in Environmental Dust.

This study introduces a novel surface-enhanced Raman spectroscopy (SERS)-based lateral flow test (LFT) dipstick that integrates digital analysis for highly sensitive and rapid viral quantification. The SERS-LFT dipsticks, incorporating gold-silver core-shell nanoparticle probes, enable pixel-based digital analysis of large-area SERS scans. Such an approach enables ultralow-level detection of viruses that readily distinguishes positive signals from background noise at the pixel level. The developed digital SERS-LFTs demonstrate limits of detection (LODs) of 180 fg for SARS-CoV-2 spike protein, 120 fg for nucleocapsid protein, and 7 plaque forming units for intact virus, all within <30 min. Importantly, digital SERS-LFT methods maintain their robustness and their LODs in the presence of indoor dust, thus underscoring their potential for accurate and reliable virus diagnosis and quantification in real-world environmental settings.

A new tau dephosphorylation-targeting chimera for the treatment of tauopathies.

Abnormal accumulation of hyperphosphorylated tau protein plays a pivotal role in a collection of neurodegenerative diseases named tauopathies, including Alzheimer's disease (AD). We have recently conceptualized the design of hetero-bifunctional chimeras for selectively promoting the proximity between tau and phosphatase, thus specifically facilitating tau dephosphorylation and removal. Here, we sought to optimize the construction of tau dephosphorylating-targeting chimera (DEPTAC) and obtained a new chimera D14, which had high efficiency in reducing tau phosphorylation both in cell and tauopathy mouse models, while showing limited cytotoxicity. Moreover, D14 ameliorated neurodegeneration in primary cultured hippocampal neurons treated with toxic tau-K18 fragments, and improved cognitive functions of tauopathy mice. These results suggested D14 as a cost-effective drug candidate for the treatment of tauopathies.

Percutaneous Nephrolithotomy Versus Open Surgery in the Treatment of Urinary Calculi.

Objective: To evaluate the effectiveness of percutaneous nephrolithotomy (PCNL) compared with open surgery for urinary stone removal. Methods: A total of 95 patients with urinary stones were screened for eligibility between October 2020 and December 2021. After excluding 5 patients who revoked their consent, 90 patients were randomized to receive either traditional open surgery (traditional group) or PCNL (PCNL group), with 45 patients in each group. In addition, the two groups received Shugan Qingre Tonglin decoction twice daily for 2 weeks. Outcome measures included intraoperative indexes, stone removal rate, postoperative healing, and quality of life. Results: PCNL resulted in significantly better intraoperative indexes (95% CI, 0.49-1.11; P < .001), lower creatinine concentration (95% CI, 0.59-1.61; P < .001), and higher glomerular filtration rate (95% CI, 2.43-2.91; P < .001) compared with traditional open surgery. Patients in the PCNL group had a significantly higher stone removal rate (95% CI, 1.09-2.51; P < .001) and a lower incidence of adverse events (95% CI, 0.69-1.87; P < .001) compared with those receiving traditional open surgery. Patients in the PCNL group had significantly higher quality of life (95% CI, 1.39-2.81; P < .001) and significantly higher maximum urinary flow rate (95% CI, 1.36-2.61; P < .001) than those in the traditional group at 1 month and 3 months after treatment. Conclusion: PCNL provides better postoperative renal function improvement, enhances the postoperative recovery of patients with urinary stones, and features manageable safety compared with traditional open surgery. The benefits of PCNL make it a promising technique for the clinical management of urinary stones. Its minimally invasive nature reduces patient discomfort, promotes faster recovery, and improves overall patient satisfaction. The superior outcomes of PCNL in terms of renal function improvement and postoperative recovery suggest that it is a viable alternative to traditional open surgery. Further research and clinical trials are warranted to validate these findings and establish PCNL as a widely adopted approach in the field of urology.

Meta-Analysis of Efficacy of Platelet-Rich Plasma Combined with Minoxidil for Androgenetic Alopecia.

BACKGROUND: Androgenetic alopecia (AGA) is a prevalent type of hair loss that impacts individuals of both genders. Platelet-rich plasma (PRP) and minoxidil have been employed as therapeutic interventions for AGA, yet the efficacy of their concurrent use remains ambiguous. OBJECTIVE: To perform a comprehensive review and meta-analysis aimed at evaluating the effectiveness of platelet-rich plasma (PRP) in combination with minoxidil for the treatment of androgenetic alopecia (AGA). METHODS: We conducted a comprehensive search of the databases PubMed, Embase, Web of Science, and Cochrane Library, encompassing their complete records up until December 2023. Eligible studies were randomized controlled trials that compared the combination of PRP and minoxidil with minoxidil or PRP alone in patients with AGA. The primary outcome measure was the change in hair growth as assessed by the hair density or hair thickness. Secondary outcome measures included patient satisfaction, and global photographic assessment. RESULTS: A total of 6 studies involving 343 participants were included in this meta-analysis. The results showed that PRP combined with minoxidil significantly improved hair growth compared to minoxidil or PRP alone. The pooled analysis demonstrated a significant increase in hair density (weighted mean difference [WMD] = 9.14; 95% confidence interval [CI]: 6.57-11.70) and hair diameter (WMD = 4.72; 95% CI 3.21-6.23) in the PRP combined with minoxidil group. Moreover, patients receiving PRP combined with minoxidil reported higher satisfaction rates compared to those using minoxidil or PRP alone. CONCLUSIONS: This meta-analysis suggests that PRP combined with minoxidil is an effective treatment for AGA, providing significant improvement in hair growth and patient satisfaction. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Magnetic MoS2/Fe3O4 composite as an effective activator of persulfate for the degradation of tetracycline: performance, activation mechanisms and degradation pathways.

The activated persulfate (PS) process could produce sulfate radical (SO4·-) and rapidly degrade organic pollutants. The application of Fe3O4 as a promising PS activator was limited due to the rapid conversion of Fe2+ to Fe3+ on its surface. Mo4+ on MoS2 surface could be used as a reducing site to convert Fe3+ to Fe2+, but the separation and recovery of MoS2 was complex. In this study, MoS2/Fe3O4 was prepared to accelerate the Fe3+/Fe2+ cycle on Fe3O4 surface and achieved efficient separation of MoS2. The results showed that MoS2/Fe3O4 was more effective for PS activation compared to Fe3O4 or MoS2, with a removal efficiency of 91.8% for 20 mg·L-1 tetracycline (TC) solution under the optimal conditions. Fe2+ and Mo4+ on MoS2/Fe3O4 surface acted as active sites for PS activation with the generation of SO4•-, •OH, •O2-, and 1O2. Mo4+ acted as an electron donor to promote the Fe3+/Fe2+ cycling and thus improved the PS activation capability of MoS2/Fe3O4. The degradation pathways of TC were inferred as hydroxylation, ketylation of dimethylamino group and C-N bond breaking. This study provided a promising activated persulfate-based advanced oxidation process for the efficient degradation of TC by employing MoS2/Fe3O4 as an effective activator.

[Oblique Lumbar Interbody Fusion Combined With 4-Screw Fixation for Treating Two-Level Degenerative Lumbar Diseases:A Finite Element Study].

Objective To demonstrate the feasibility of oblique lumbar interbody fusion (OLIF) combined with 4-screw fixation for treating two-level lumbar degenerative diseases.Methods An intact finite element model of L3-S1 (M0) was constructed and validated.Then,we constructed the M1 model by simulating OLIF surgery at L3/4 and L4/5 segments on the M0 model.By attachment of posterior 4-screw or 6-screw fixation to the M1 model,three 4-screw fixation models (M2-M4) and one 6-screw fixation model (M5) were established.The segmental and overall range of motion (ROM) and the peak von Mises stresses of superior endplate,cage,and posterior screw-rod were investigated under each implanted condition.Results Under the motion modes of forward flexion,backward extension,bilateral (left and right) flexion,and left and right rotation,the L3/4 ROM of M2 model and L4/5 ROM of M3 model increased,while the L3/4 and L4/5 ROM of M4 and M5 models significantly decreased compared with those of M1 model.Under all motion modes,the L4 superior endplate in M2 model and the L5 superior endplate in M3 model showed the maximum peak von Mises stress,and the peak von Mises stresses of L4 and L5 superior endplates in M4 and M5 models were close.The L3/4 cage in M2 model and the L4/5 cage in M3 model showcased the largest peak von Mises stress,and the peak von Mises stresses of cages in M4 and M5 models were close.The peak stresses of internal fixation in M2-M5 models were close.Conclusion Four-screw fixation can replace 6-screw fixation in the OLIF surgery for treating two-level degenerative lumbar diseases.

[Correlation of anti-C1q antibodies with active systemic lupus erythematosus and lupus nephritis in children]. / 抗C1qæŠ—ä½“ä¸Žå„¿ç«¥æ´»åŠ¨æ€§ç³»ç»Ÿæ€§çº¢æ–‘ç‹¼ç–®å’Œæ´»åŠ¨æ€§ç‹¼ç–®æ€§è‚¾ç‚Žçš„ç›¸å ³æ€§åˆ†æž.

OBJECTIVES: To study the correlation of anti-C1q antibodies with active systemic lupus erythematosus (SLE) and lupus nephritis (LN) in children, as well as their diagnostic value for active SLE and LN. METHODS: A retrospective selection of 90 hospitalized children with SLE at the Children's Medical Center of Second Xiangya Hospital, Central South University from January 2016 to March 2019 as the SLE group, all of whom were tested for anti-C1q antibodies. A control group was formed by collecting 70 hospitalized children with other autoimmune diseases (OAD) during the same period. The differences in anti-C1q antibody levels were compared between two groups.The correlation of anti-C1q antibodies with various indicators of SLE and LN was analyzed, and the diagnostic value of anti-C1q in SLE and LN was evaluated. RESULTS: The serum levels of anti-C1q antibodies in the SLE group were higher than those in the OAD group (P<0.05). The SLE disease activity index score was positively correlated with anti-C1q antibodies (rs=0.371, P<0.001) and positively correlated with anti-double-stranded DNA antibodies (rs=0.370, P<0.001). The sensitivity and specificity of anti-C1q antibodies for diagnosing active SLE were 89.90% and 53.90%, respectively, with an area under the curve of 0.720 (P<0.05) and a critical value of 5.45 U/mL. The sensitivity and specificity of anti-C1q antibody levels for diagnosing active LN were 58.50% and 85.00%, respectively, with an area under the curve of 0.675 (P<0.05) and a critical value of 22.05 U/mL. CONCLUSIONS: Anti-C1q antibodies can serve as non-invasive biomarkers for evaluating the activity of SLE or predicting the activity of LN in children.

[Clinical characteristics of children with anti-neutrophil cytoplasmic antibody-associated vasculitis]. / å„¿ç«¥æŠ—ä¸­æ€§ç²’ç»†èƒžèƒžè´¨æŠ—ä½“ç›¸å ³æ€§è¡€ç®¡ç‚Žä¸´åºŠç‰¹å¾åˆ†æž.

OBJECTIVES: To study the clinical characteristics of children with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: A retrospective analysis was conducted on the clinical data of 25 children diagnosed with AAV at the Second Xiangya Hospital of Central South University from January 2010 to June 2022. RESULTS: Among the AAV children, there were 5 males and 20 females, with a median age of onset of 11.0 years. Involvement of the urinary system was seen in 18 cases (72%); respiratory system involvement in 10 cases (40%); skin involvement in 6 cases (24%); eye, ear, and nose involvement in 5 cases (20%); joint involvement in 4 cases (16%); digestive system involvement in 2 cases (8%). Eleven cases underwent kidney biopsy, with 5 cases (46%) showing focal type, 2 cases (18%) showing crescentic type, 2 cases (18%) showing mixed type, and 2 cases (18%) showing sclerotic type. Immune complex deposits were present in 5 cases (45%). Seven cases reached chronic kidney disease (CKD) stage V, with 2 cases resulting in death. Two cases underwent kidney transplantation. At the end of the follow-up period, 2 cases were at CKD stage II, and 1 case was at CKD stage III. Of the 16 cases of microscopic polyangiitis (MPA) group, 13 (81%) involved the urinary system. Of the 9 cases of granulomatosis with polyangiitis (GPA), 6 cases (66%) had sinusitis. Serum creatinine and uric acid levels were higher in the MPA group than in the GPA group (P<0.05), while red blood cell count and glomerular filtration rate were lower in the MPA group (P<0.05). CONCLUSIONS: AAV is more common in school-age female children, with MPA being the most common clinical subtype. The onset of AAV in children is mainly characterized by renal involvement, followed by respiratory system involvement. The renal pathology often presents as focal type with possible immune complex deposits. Children with MPA often have renal involvement, while those with GPA commonly have sinusitis. The prognosis of children with AAV is poor, often accompanied by renal insufficiency.

A novel off-line multi-dimensional high-speed countercurrent chromatography strategy for preparative separation of bioactive neolignan isomers from Piper betle. L.

Separation and purification of naturally occurring isomers from herbs are still challenging. High-speed counter-current chromatography (HSCCC) has been applied to isolate natural products. In this study, an off-line multi-dimensional high-speed counter-current chromatography (multi-D HSCCC) strategy was developed utilizing the in situ concentration technique with online storage recycling elution to rapidly separate bioactive isomeric neolignans from chloroform-partitioned samples of the plant Piper betle L. In the procedure, the crude sample (105 mg) was implemented using the online storage recycling technique in a two-phase solvent system composed of petroleum ether-ethyl acetate-methanol-water (7: 5: 12: 3), which first simply afforded a neolignane kadsurenone (1, 5.3 mg) and its epimer (-)-denudatin B (2, 6.4 mg). Then, the remains fr a was subjected to the second-dimensional HSCCC elution using the in situ concentration technique with online storage recycling technique in another solvent system of petroleum ether-ethyl acetate-methanol-water (5: 5: 11, 15). As a result, kadsurenin I (3, 0.6 mg) and its regioisomer pibeneolignan C (4, 5.0 mg), together with the fractional remaining fr b and fr c, were obtained. Thirdly, the fr c was reloaded to allow the HSCCC for recycling elution with the former solvent system employing the in situ concentration strategy and yielded a pair of epimers, (7R,8S,1'S)-1'-allyl-5-methoxy-8-methyl-7-piperonyl-7,8,3,6-tetrahydro-2-oxobenzofuran (5, 10.2 mg), and 3-epi-(-)-burchullin (6, 2.6 mg). Finally, the three pairs of less amount and the structurally similar isomers 1-6 were isolated from the crude fraction of P. betle with a high HPLC purity of over 95.0 % for compound 2, 4-6 and 92.5 % for compound 1, 91.0 % for 3, while the purity of 1 and 3 in 1H NMR were 89.9 % and 91.1 %, respectively. The whole isolation process was quick and efficient. Compounds 1, 2, 4 and 5 showed significantly synergistic activities combining several antibiotics against five drug-resistant Staphylococcus aureus with FICIs from 0.156 to 0.375. This novel off-line multi-dimensional HSCCC strategy could be broadened to application for the rapid separation of complex natural products.

Cadherin-11 targeted cell-specific liposomes enabled skin fibrosis treatment by inducing apoptosis.

Continuous and aberrant activation of myofibroblasts is the hallmark of pathological fibrosis (e.g., abnormal wound healing). The deposition of excessive extracellular matrix (ECM) components alters or increases the stiffness of tissue and primarily accounts for multiple organ dysfunctions. Among various proteins, Cadherin-11 (CDH11) has been reported to be overexpressed on myofibroblasts in fibrotic tissues. Anti-apoptotic proteins such as (B cell lymphoma-2) (BCL-2) are also upregulated on myofibroblasts. Therefore, we hypothesize that CDH11 could be a targeted domain for cell-specific drug delivery and targeted inhibition of BCL-2 to ameliorate the development of fibrosis in the skin. To prove our hypothesis, we have developed liposomes (LPS) conjugated with CDH11 neutralizing antibody (antiCDH11) to target cell surface CDH11 and loaded these LPS with a BCL-2 inhibitor, Navitoclax (NAVI), to induce apoptosis of CDH11 expressing fibroblasts. The developed LPS were evaluated for physicochemical characterization, stability, in vitro therapeutic efficacy using dermal fibroblasts, and in vivo therapeutic efficacy in bleomycin-induced skin fibrosis model in mice. The findings from in vitro and in vivo studies confirmed that selectivity of LPS was improved towards CDH11 expressing myofibroblasts, thereby improving therapeutic efficacy with no indication of adverse effects. Hence, this novel research work represents a versatile LPS strategy that exhibits promising potential for treating skin fibrosis.

Staphylococcus Aureus Membrane Vesicles Kill Tumor Cells Through a Caspase-1-Dependent Pyroptosis Pathway.

Introduction: Nanosized outer membrane vesicles (OMVs) from Gram-negative bacteria have attracted increasing interest because of their antitumor activity. However, the antitumor effects of MVs isolated from Gram-positive bacteria have rarely been investigated. Methods: MVs of Staphylococcus aureus USA300 were prepared and their antitumor efficacy was evaluated using tumor-bearing mouse models. A gene knock-in assay was performed to generate luciferase Antares2-MVs for bioluminescent detection. Cell counting kit-8 and lactic dehydrogenase release assays were used to detect the toxicity of the MVs against tumor cells in vitro. Active caspase-1 and gasdermin D (GSDMD) levels were determined using Western blot, and the tumor inhibition ability of MVs was determined in B16F10 cells treated with a caspase-1 inhibitor. Results: The vesicular particles of S. aureus USA300 MVs were 55.23 ± 8.17 nm in diameter, and 5 µg of MVs remarkably inhibited the growth of B16F10 melanoma in C57BL/6 mice and CT26 colon adenocarcinoma in BALB/c mice. The bioluminescent signals correlated well with the concentrations of the engineered Antares2-MVs (R2 = 0.999), and the sensitivity for bioluminescence imaging was 4 × 10-3 µg. Antares2-MVs can directly target tumor tissues in vivo, and 20 µg/mL Antares2-MVs considerably reduced the growth of B16F10 and CT26 tumor cells, but not non-carcinomatous bEnd.3 cells. MV treatment substantially increased the level of active caspase-1, which processes GSDMD to trigger pyroptosis in tumor cells. Blocking caspase-1 activation with VX-765 significantly protected tumor cells from MV killing in vitro and in vivo. Conclusion: S. aureus MVs can kill tumor cells by activating the pyroptosis pathway, and the induction of pyroptosis in tumor cells is a promising strategy for cancer treatment.

6-Gingerol ameliorates alveolar hypercoagulation and fibrinolytic inhibition in LPS-provoked ARDS via RUNX1/NF-κB signaling pathway.

BACKGROUND: Alveolar hypercoagulation and fibrinolytic inhibition play a central role in refractory hypoxemia in acute respiratory distress syndrome (ARDS), but it lacks effective drugs for prevention and treatment of this pathophysiology. Our previous experiment confirmed that RUNX1 promoted alveolar hypercoagulation and fibrinolytic inhibition through NF-κB pathway. Other studies demonstrated that 6-gingerol regulated inflammation and metabolism by inhibiting the NF-κB signaling pathway. We assume that 6-gingerol would ameliorate alveolar hypercoagulation and fibrinolytic inhibition via RUNX1/ NF-κB pathway in LPS-induced ARDS. METHODS: Rat ARDS model was replicated through LPS inhalation. Before LPS inhalation, the rats were intraperitoneally treated with different doses of 6-gingerol or the same volume of normal saline (NS) for 12 h, and then intratracheal inhalation of LPS for 24 h. In cell experiment, alveolar epithelial cell type II (AECII) was treated with 6-gingerol for 6 h and then with LPS for another 24 h. RUNX1 gene was down-regulated both in pulmonary tissue and in cells. Tissue factor (TF), plasminogen Activator Inhibitor 1(PAI-1) and thrombin were determined by Wester-blot (WB), qPCR or by enzyme-linked immunosorbent (ELISA). Lung injury score, pulmonary edema and pulmonary collagen III in rat were assessed. NF-κB pathway were also observed in vivo and in vitro. The direct binding capability of 6-gingerol to RUNX1 was confirmed by using Drug Affinity Responsive Target Stability test (DARTS). RESULTS: 6-gingerol dose-dependently attenuated LPS-induced lung injury and pulmonary edema. LPS administration caused excessive TF and PAI-1 expression both in pulmonary tissue and in AECII cell and a large amount of TF, PAI-1 and thrombin in bronchial alveolar lavage fluid (BALF), which all were effectively decreased by 6-gingerol treatment in a dose-dependent manner. The high collagen Ⅲ level in lung tissue provoked by LPS was significantly abated by 6-gingerol. 6-gingerol was seen to dramatically inhibit the LPS-stimulated activation of NF-κB pathway, indicated by decreases of p-p65/total p65, p-IKKß/total IKKß, and also to suppress the RUNX1 expression. RUNX1 gene knock down or RUNX1 inhibitor Ro5-3335 significantly enhanced the efficacies of 6-gingerol in vivo and in vitro, but RUNX1 over expression remarkably impaired the effects of 6-gingerol on TF, PAI-1 and on NF-κB pathway. DARTS result showed that 6-gingerol directly bond to RUNX1 molecules. CONCLUSIONS: Our experimental data demonstrated that 6-gingerol ameliorates alveolar hypercoagulation and fibrinolytic inhibition via RUNX1/NF-κB pathway in LPS-induced ARDS. 6-gingerol is expected to be an effective drug in ARDS.

Advanced tetracyclic heat-resistant energetic materials based on bis(4-nitropyrazole) bridged 1,2,4-triazole.

In recent years, with the development of deep coal mines and petroleum resources and the expansion of the aerospace industry, the pursuit of heat-resistant energetic materials with high thermal stability and high energy has been increasing. Bis(4-nitropyrazole) was employed as an energy bridge to link 1,2,4-triazole, thereby constructing a sophisticated tetracyclic framework in this study. A tetracyclic heat-resistant explosive 5,5'-(4,4'-dinitro-2H,2'H-[3,3'-bipyrazole]-5,5'-diyl)bis(4H-1,2,4-triazole-3,4-diamine) (3) and its derivatives 6-8 with excellent comprehensive performance have been successfully prepared. Particularly noteworthy is that compound 3 has a detonation velocity of 8604 m s-1, which exceeds that of the conventional heat-resistant explosive HNS with a velocity of 7164 m s-1. Furthermore, compound 3 has higher thermal stability (Td = 340 °C) than HNS (Td = 318 °C). In addition, the tetracyclic compound 3 also exhibited extraordinarily low sensitivity (IS > 40 J; FS > 360 N). These unique characteristics make it a potential candidate for novel heat-resistant and insensitive energetic materials.

Multi-spectroscopies and molecular docking insights into the interaction mechanism and antioxidant activity of isoquercetin and zein nanoparticles.

The purpose of this study was to compare and characterize the theoretical properties and interaction mechanisms of zein and isoquercetin (ISO) from experimental and theoretical perspectives. Zein nanoparticles with different ISO concentrations (ZINPs) were prepared by the antisolvent precipitation method. The experimental results indicated all particles appeared spherical. When the mass ratio of zein to ISO was 10:1, the encapsulation efficiency of ZINPs reached 88.19 % with an average diameter of 126.67 nm. The multispectral method and molecular docking results confirmed that hydrogen bonding and van der Waals force played a dominant role for the binding of ISO to zein, and the primary fluorescence quenching mechanism for zein by ISO was static quenching. Furthermore, ZINPs had greater solubility and antioxidant activity, as well as inhibited the release of ISO during simulated gastrointestinal digestion processes. This research contributes to the understanding of the non-covalent binding mechanism between zein and ISO, providing a theoretical basis for the construction of ISO active carriers.

Ankylosing spondylitis coexisting with Clonorchis sinensis infection: A case report.

BACKGROUND: Ankylosing spondylitis (AS) is a chronic immune-mediated inflammatory disease. The prevailing theory links AS onset to infections in susceptible individuals. Furthermore, infections may impair the immune responses. Numerous studies have investigated links between AS and various infections-bacterial, viral, fungal, and other microorganism infections. However, limited attention has been given to the association between AS and Clonorchis sinensis (C. sinensis) infection. CASE SUMMARY: A 27-year-old male with a 10-yr history of AS presented to our hospital with inflammatory lower back pain as the primary manifestation. Ten years ago, the patient had achieved a stable condition after treatment with biological agents. However, he experienced a recurrence of lumbosacral pain with an unexplained cause 10 d before hospital admission. A lumbosacral magnetic resonance imaging (MRI) scan revealed bone marrow edema in the left sacroiliac joint, and laboratory indicators were elevated. Moreover, the presence of C. sinensis eggs was detected in the stool. The patient was prescribed praziquantel, resulting in the disappearance of C. sinensis eggs in subsequent routine stool tests and relief from lumbosacral pain. A follow-up MRI scan performed after 4 months revealed a reduction in bone marrow edema around the left sacroiliac joint. CONCLUSION: C. sinensis infections could potentially trigger the exacerbation of AS. Clinicians should pay attention to investigating the presence of infections.

Effect of hydrochloric acid and citric acid with ultrasound processing on characteristics of superfine-ground pectic polysaccharides from okra (Abelmoschus esculentus L.) peel.

The structural properties and biological activities of okra pectic polysaccharides (OPs) were impacted by various extraction methods. Based on commonly grinding (40, 100 meshes) and superfine grinding okra powders, two extraction solvents (hydrochloric acid, HA; citric acid, CA) were used firstly. Next, the extraction yield, physical and chemical properties, molecular structure and functional properties of OPs were analyzed by non-ultrasonic treatment and ultrasound-assisted superfine grinding method. The outcomes demonstrated that the extraction yield of OPs rose as the particle size of the powder decreased. HA-OPs had higher molecular weight (Mw), apparent viscosity and emulsification ability than CA-OPs. CA-OPs had higher esterification degree (DE), solubility and total sugar content, and higher amounts of rhamnogalacturonan-I (RG-I) segments. Compared with OPs without ultrasound-assisted extraction, ultrasound-assisted superfine grinding extraction exhibited higher sugar content, antioxidant capacity, emulsification ability, lower Mw, DE and apparent viscosity. Finally, the correlation between structure and function of OPs was further quantified. The antioxidant capacity was positively correlated with RG-I content, and negatively correlated with DE and Mw. The emulsification ability was mainly positively correlated with the GlcA of OPs. This study provides a theoretical basis for the development of OPs foods with clear structure-function relationship, which would be instructive for the application of OPs in food and cosmetics.

Identification of antidepressant constituents from Xiangfu-chuanxiong herbal medicine pair via spectrum-effect relationship analyses, molecular docking and corticosterone-induced PC12 cells.

Herbal medicine pair, composed of two single herbs, is a relatively fixed minimum prescription unit in the traditional Chinese medicine's formula and has special significance in clinic. The combination of Xiangfu (the rhizoma of Cyperus rotundus L, XF) and Chuanxiong (the rhizoma of Ligusticum chuanxiong Hort, CX) has been recoded as an herbal medicine pair XF-CX in the Yuan Dynasty (1347 CE) of China and widely used in traditional Chinese medicine formula, including Chaihu Shugan San, which has been clinically used for treatment of depression. However, the optimal ratio of the XF-CX herbal medicine pair and its antidepressant constituents are still unclear. Herein, the antidepressive-like effects of XF-CX herbal medicine pairs with different ratios of XF and CX (2:1, 1:1, 1:2) were evaluated using behavioral despair animal models in mice, and then its potential antidepressant constituents were recognized by spectrum-effect relationship analyses. Finally, the potential antidepressant constituents of the XF-CX herbal medicine pair were validated by molecular docking with glucocorticoid receptor and corticosterone (CORT)-induced PC12 cell injury model. The results indicated that different ratios of XF-CX pairs had antidepressive-like effects, and the XF-CX (2:1) exhibited a more significant effect. Thirty-two potential antidepressant constituents in the XF-CX herbal medicine pair were screened out from the spectrum-effect relationship combined molecular docking analyses. Among them, senkyunolide A, cyperotundone, Z-ligustilide, and levistilide A were validated to have protective effects against CORT-induced injury in PC12 cells. Our findings not only obtained the optimal ratio of XF-CX in the herbal medicine pair for the treatment of depression but also its potential antidepressant constituents, which will benefit in elucidating the mechanism of action and promoting the application of the herbal medicine pair in the clinic.