Reactive Force Field Molecular Dynamics Investigation of NH3 Generation Mechanism during Protein Pyrolysis Process.

The mechanism of ammonia formation during the pyrolysis of proteins in biomass is currently unclear. To further investigate this issue, this study employed the AMS 2023.104 software to select proteins (actual proteins) as the model compounds and the amino acids contained within them (assembled amino acids) as the comparative models. ReaxFF molecular dynamics simulations were conducted to explore the nitrogen transformation and NH3 generation mechanisms in three-phase products (char, tar, and gas) during protein pyrolysis. The research results revealed several key findings. Regardless of whether the model compounds are actual proteins or assembled amino acids, NH3 is the primary nitrogen-containing product during pyrolysis. However, as the temperature rises to higher levels, such as 2000 K and 2500 K, the amount of NH3 decreases significantly in the later stages of pyrolysis, indicating that it is being converted into other nitrogen-bearing species, such as HCN and N2. Simultaneously, we also observed significant differences between the pyrolysis processes of actual proteins and assembled amino acids. Notably, at 2000 K, the amount of NH3 generated from the pyrolysis of assembled amino acids was twice that of actual proteins. This discrepancy mainly stems from the inherent structural differences between proteins and amino acids. In proteins, nitrogen is predominantly present in a network-like structure (NH-N), which shields it from direct external exposure, thus requiring more energy for nitrogen to participate in pyrolysis reactions, making it more difficult for NH3 to form. Conversely, assembled amino acids can release NH3 through a simpler deamination process, leading to a significant increase in NH3 production during their pyrolysis.

An Optimized Method for Evaluating the Preparation of High-Quality Fuel from Various Types of Biomass through Torrefaction.

The pretreatment for torrefaction impacts the performance of biomass fuels and operational costs. Given their diversity, it is crucial to determine the optimal torrefaction conditions for different types of biomass. In this study, three typical solid biofuels, corn stover (CS), agaric fungus bran (AFB), and spent coffee grounds (SCGs), were prepared using fluidized bed torrefaction. The thermal stability of different fuels was extensively discussed and a novel comprehensive fuel index, "displacement level", was analyzed. The functional groups, pore structures, and microstructural differences between the three raw materials and the optimally torrefied biochar were thoroughly characterized. Finally, the biomass fuel consumption for household heating and water supply was calculated. The results showed that the optimal torrefaction temperatures for CS, AFB, and SCGs were 240, 280, and 280 °C, respectively, with comprehensive quality rankings of the optimal torrefied biochar of AFB (260) > SCG (252) > CS (248). Additionally, the economic costs of the optimally torrefied biochar were reduced by 7.03-19.32%. The results indicated that the displacement level is an index universally applicable to the preparation of solid fuels through biomass torrefaction. AFB is the most suitable solid fuel to be upgraded through torrefaction and has the potential to replace coal.

A novel surgical strategy of three column osteotomy at non-lesioned area for correcting severe angular kyphosis due to Pott's disease: a retrospectively study.

Severe sharp angular kyphosis resulting from Pott's disease typically necessitates surgical intervention. The deployment of three-column osteotomy within the lesion and apical regions has been validated as an effective modality for the amelioration of angular kyphosis. Nonetheless, a propensity for residual kyphosis persists, accompanied by a significant perioperative risk profile. In pursuit of optimizing correctional outcomes and diminishing complication rates, we proposed an innovative surgical approach, utilizing osteotomy in the non-lesioned zones for the rectification of severe angular kyphosis associated with Pott's disease. This retrospective investigation encompasses 16 subjects who underwent this novel surgical tactic, involving osteotomies in non-lesioned vertebral segments, at our institution from 2016 to 2018. Radiographic measures, encompassing kyphotic angle and sagittal vertical axis (SVA), were documented at baseline and during terminal follow-up. Neurological status was evaluated via the American Spinal Injury Association (ASIA) grading system. Operative duration, volume of hemorrhage, and perioperative complications were systematically recorded. The cohort included 6 males and 10 females with an average age of 30.7 ± 11.41 years. Follow-up intervals spanned 24 to 42 months. Mean operative time and blood loss were 492 ± 127.3 min and 1791 ± 788.8 ml, respectively. The kyphotic angle improved from 97.6 ± 14.6° to 28.8 ± 18.70°. In cases with lumbar afflictions, vertebral restoration was achieved (L1-L5 and L2-S1). Initial mean SVA of 6.7 ± 3.58 cm was reduced to 3.3 ± 1.57 cm at follow-up. Neurological function enhancement was observed in six patients, while ten maintained baseline status. Complication rates, including wound infection and rod fracture at 12 months, were observed in approximately 11.8% of cases. Our findings suggest that the surgical strategy is both effective and safe for addressing severe angular kyphosis due to Pott's disease, contingent upon the expertise of the surgical unit.

Association between the fetal-type posterior cerebral artery and intracranial anterior and posterior circulating atherosclerotic plaques using multi-contrast magnetic resonance vessel wall imaging.

Background: Intracranial atherosclerotic disease (ICAD) is one of the most common causes of ischemic stroke. The fetal-type posterior cerebral artery (FTP) affects intracranial collateral circulation, which is closely related to the occurrence and development of ICAD. Knowledge of the relationship between FTP and ICAD is important for developing treatment strategies for FTP patients diagnosed with atherosclerotic diseases. This study aims to quantitatively analyze the association between the FTP and intracranial atherosclerotic plaques using magnetic resonance vessel wall imaging (VW-MRI). Methods: This retrospective study enrolled patients with recent cerebrovascular symptoms (stroke or transient ischemic attack <2 weeks) who were diagnosed with atherosclerotic plaque(s) by VW-MRI in one hospital from October 2018 to March 2022. They were classified into the FTP group and the non-FTP group. Plaque characteristics and vascular-related parameters in intracranial arteries were compared between the two groups. Univariate and multivariate logistic regressions were performed to determine the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) of the plaque characteristics between the two groups. Results: A total of 104 patients (mean age: 61.8±9.8 years, 57 males) were included for VW-MRI scan analysis. 40 (38.46%) and 64 (61.54%) were classified into the FTP and the non-FTP groups, respectively. The plaques of middle cerebral artery (MCA) in the FTP group were more likely to occur on the dorsal and superior walls of the lumen compared with the non-FTP group (37.50% vs. 17.19%, P=0.001). The remodeling index (RI) of MCA was statistically different between the two groups (1.071±0.267 vs. 0.886±0.235, P=0.007). No significant differences were found in vertebrobasilar artery (VBA) plaque distributions (17.50% vs. 9.38%, 10.00% vs. 12.50%, 20.00% vs. 17.19%, P>0.05) and characteristics between the two groups (RI: 1.095±0.355 vs. 0.978±0.251; eccentricity index: 0.539±1.622 vs. 0.550±0.171, P>0.05). Conclusions: The plaques in the FTP group were more likely to occur on the dorsal and superior walls of the MCA, and the presentence of FTP was found to be significantly correlated with vascular remodeling of MCA atherosclerotic plaques. The relationship between the severity of intracranial atherosclerosis and the presence of FTP can provide valuable information for clinicians to intervene early and prevent the occurrence of stroke.

HKDC1 in Gastric Cancer: A New Diagnostic, Prognostic Biomarker, and Novel Therapeutic Target.

OBJECTIVE: Gastric cancer (GC) has become a significant contributor globally to cancer-related mortalities. Accordingly, there is a critical need to identify a new therapeutic target for GC. Recently, the hexokinase domain containing 1 (HKDC1), an oncogenic factor, has been recognized in various cancers. Nevertheless, the role of HKDC1 in GC still needs to be explored. This study is aimed to investigate the role of HKDC1 in GC. METHODS: Initially, the HKDC1 expression in GC tissue samples and cell lines was analyzed using RT-qPCR, exploring its correlation with overall patient survival. Further, short hairpin RNA (shRNA) technology was employed to establish HKDC1 knockdown in GC cell lines and assess the impact of HKDC1 deficiency on tumor growth in vitro and in vivo. RESULTS: RT-qPCR results revealed overexpression of HKDC1 in GC tissue samples and cell lines, which could be correlated to shorter patient survival. HKDC1 knockdown led to decreased viability and colony formation ability of GC cells. Moreover, the transwell assay demonstrated that downregulating HKDC1 significantly suppressed the migration and invasion abilities of GC cells. Eventually, the xenograft tumor model derived from HKDC1 knockdown GC cells in mice exhibited reduced tumor size and deprived Ki67 expression, indicating inhibited tumor growth. CONCLUSION: The study provided evidence of HKDC1 dysregulation in GC tissues, suggesting its potential as a promising novel target for GC treatment.

Pulmonary and clinical outcomes of patients with severe rigid scoliosis and type I respiratory failure treated with halo-pelvic distraction.

BACKGROUND: The severe rigid scoliosis patients with type I respiratory failure could not tolerate complicated corrective surgery. Preoperative halo-pelvic distraction (HPD) is used to reduce the curve magnitude and improve the pulmonary function before surgery. The present study aimed to retrospectively analyze the pulmonary and clinical outcomes of preoperative HPD in severe rigid spinal deformity with type I respiratory failure. METHODS: Eighteen cases of severe rigid scoliosis and type I respiratory failure treated with preoperative HPD and corrective surgery for spinal deformity between 2016 and 2018 were retrospectively reviewed. Patient demographics, major coronal curve and kyphosis, correction rates, heights, pulmonary function, distraction time, and postoperative neurological complications were recorded for all cases. RESULTS: The averaged duration of distraction was 9.1 ± 2.3 months. The coronal curve was corrected from 168° ± 14° to 58° ± 11° at the end of HPD. The kyphosis curve reduced from 151° ± 29° to 65° ± 10°. Meanwhile, the mean stand body height increased by 23.9 ± 5.3 cm. Significantly increased mean FVC (1.52 ± 0.43 L vs. 0.95 ± 0.44 L) and improved percent-predicted values for FVC (37 ± 10% vs. 23 ± 9%) were observed after HPD. The pressure of oxygen (PaO2) increased from 54.5 ± 2.0 to 84.8 ± 4.7 mmHg. Scoliosis and kyphosis curve, respectively, averaged 48 ± 8°and 30 ± 14° after final fusion and instrumentation, with a mean correction of 71% and 80%, respectively. No severe complication occurred during the distraction. CONCLUSIONS: HPD may be useful for severe rigid scoliosis patients with type I respiratory failure. Pulmonary functions in patients with severe rigid scoliosis can be significantly improved by HPD. They are then better able to tolerate complicated corrective surgery.

Association of culprit plaque enhancement ratio, hypoperfusion and HbA1c with recurrent ischemic stroke in patients with atherosclerotic stenosis of the middle cerebral artery.

PURPOSE: To investigate the differences in intracranial culprit plaque characteristics of the middle cerebral artery (MCA), collateral circulation and hypoperfusion in patients with and without recurrent ischemic stroke and to identify the association with the recurrent ischemic cerebrovascular events. METHOD: Eighty-six patients with acute/subacute ischemic stroke caused by atherosclerotic plaques of the MCA were retrospectively enrolled and grouped into patients with recurrence (n = 36) and without recurrence (n = 50). All patients underwent high-resolution vessel wall imaging and dynamic susceptibility contrast-enhanced perfusion weighted imaging. The differences in culprit plaque characteristics, collateral circulation and hypoperfusion in the territory of the stenotic MCA were assessed between the two groups. The relationship between plaque characteristics and hypoperfusion was evaluated. The independent factors of recurrent ischemic stroke were identified by logistic regression analyses. RESULTS: Higher HbA1c, culprit plaque enhancement grade, culprit plaque enhancement ratio, and lower time to peak map based on the Alberta Stroke Program Early CT score (TTP-ASPECTS) were observed in the recurrence group(all p < 0.050). Both plaque enhancement grade and enhancement ratio were significantly associated with TTP-ASPECTS (p = 0.030 and 0.039, respectively). HbA1c, culprit plaque enhancement ratio and TTP-ASPECTS were independent factors of the recurrence of ischemic stroke (all p < 0.050). The area under the curve of the combination including the above factors (AUC = 0.819) was significantly higher than that of any variable alone after adjustment (all p < 0.050). CONCLUSIONS: Culprit plaque enhancement ratio, TTP-ASPECTS and HbA1c were independent factors of recurrent ischemic stroke. Their combination improved the accuracy in identifying the risk of recurrent ischemic stroke.

Effect and Mechanism of Sodium Butyrate on Neuronal Recovery and Prognosis in Diabetic Stroke.

Ischemic stroke is a cerebrovascular lesion caused by local ischemia and hypoxia. Diabetes mellitus (DM) is a chronic inflammatory disease that disturbs immune homeostasis and predisposes patients to ischemic stroke. The mechanism by which DM exacerbates stroke remains unclear, although it may involve disturbances in immune homeostasis. Regulatory T cells (Tregs) play a regulatory role in many diseases, but the mechanism of Tregs in diabetes complicated by stroke remains unclear. Sodium butyrate is a short-chain fatty acid that increases Treg levels. This study examined the role of sodium butyrate in the prognosis of neurological function in diabetic stroke and the mechanism by which Tregs are amplified in the bilateral cerebral hemispheres. We evaluated the brain infarct volume, observed 48-h neuronal injury and 28-day behavioral changes, and calculated the 28-day survival rate in mice. We also measured Treg levels in peripheral blood and brain tissue, recorded changes in the blood‒brain barrier and water channel proteins and neurotrophic changes in mice, measured cytokine levels and peripheral B-cell distribution in bilateral hemispheres and peripheral blood, and examined the polarization of microglia and the distribution of peripheral T-cell subpopulations in bilateral hemispheres. Diabetes significantly exacerbated the poor prognosis and neurological deficits in mice with stroke, and sodium butyrate significantly improved infarct volume, prognosis, and neurological function and showed different mechanisms in brain tissue and peripheral blood. The potential regulatory mechanism in brain tissue involved modulating Tregs/TGF-ß/microglia to suppress neuroinflammation, while that in peripheral blood involved improving the systemic inflammatory response through Tregs/TGF-ß/T cells.

Structure and anti-inflammatory activity of neo-clerodane diterpenoids from Scutellaria barbata.

Herein, 13 previously undescribed neo-clerodane diterpenoids (1-13) and 27 known analogs (14-40) were isolated from the aerial parts of Scutellaria barbata. Absolute configurations of undescribed compounds were assigned based on single-crystal X-ray diffraction analysis and comparison of experimental and circular dichroism. All isolates were evaluated for the inhibition of nitric oxide generation induced by lipopolysaccharide in RAW 264.7 macrophages. Compound 36 was found to be the most active with an IC50 value of 10.6 µM. Structure-activity relations of these neo-clerodane diterpenoids revealed that the α, ß-unsaturated-γ-lactone moiety with an exocyclic conjugated double bond was necessary for maintaining and increasing its activity. Further mechanistic studies show that compound 36 suppressed nitric oxide synthase enzymes (iNOS) expression without affecting iNOS activity. Additionally, compound 36 suppresses NF-κB signaling by inhibiting IκBα phosphorylation.

Staged osteotomy in lateral position for the treatment of severe kyphotic deformity secondary to ankylosing spondylitis: a retrospective study.

BACKGROUND: Patients with severe kyphotic deformity (Cobb > 100°) secondary to ankylosing spondylitis (AS) occasionally cannot undergo corrective surgery in the prone position. Osteotomy in the lateral position might provide a possible solution. In this study, we aim to evaluate the clinical efficacy and safety of staged osteotomy in the lateral position for the treatment of AS-related severe kyphosis with a minimum of 2-year follow-up. METHODS: In total, 23 patients who underwent staged osteotomy in the lateral position from October 2015 to June 2017 were analyzed. In the first stage of surgery, all but one patient underwent a single-level Ponte osteotomy, which was followed by a pedicle subtraction osteotomy in the second stage. Mean follow-up was 30.8 ± 4.6 months. Global kyphosis (GK), thoracic kyphosis (TK), lumbar lordosis (LL), sagittal vertical axis (SVA), osteotomized vertebra intervertebral angle (OVI), chin-brow vertical angle (CBVA), Oswestry Disability Index (ODI) score and Scoliosis Research Society-22 Patient Questionnaire (SRS-22) were all compared pre- and postoperation. RESULTS: All kyphosis parameters were significantly improved (all P < 0.05). GK was corrected from 115.0 ± 13.4° to 46.5 ± 9.0° postoperatively, with a mean correction of 68.5°. SVA was improved from 21.2 ± 5.1 cm to 5.1 ± 1.8 cm postoperatively. After surgery, CBVA was adjusted from 64.1 ± 23.2° to 5.7 ± 10.6° and OVI was changed from 9.0 ± 2.7° to - 20.1 ± 5.6°. Both the ODI and SRS-22 showed substantial improvements (all P < 0.05). Four patients with mild complications were observed perioperatively. CONCLUSION: In AS patients with severe kyphosis, satisfactory correction can be safely achieved with staged osteotomy in the lateral position, which can not only correct the sagittal imbalance of the spine with acceptable complications but also facilitate the placement of the intraoperative position.

Optimization of Briquette Fuels by Co-Torrefaction of Residual Biomass and Plastic Waste Using Response Surface Methodology.

Combining biomass, a clean and renewable energy source, with waste plastic, which serves as a good auxiliary fuel, can produce high-quality clean fuel. The performance of biomass-derived fuel can be improved by torrefaction. This study optimized the co-torrefaction of fungus bran and polypropylene (PP) waste plastic to obtain clean solid biofuel with high calorific value and low ash content (AC) using response surface methodology. Two sets of mixed biochars were investigated using a multiobjective optimization method: mass yield-higher heating value-ash content (MY-HHV-AC) and energy yield-ash content (EY-AC). PP increased the heat value, decreased AC, and acted as a binder. The optimal operating conditions regarding reaction temperature, reaction time, and PP blending ratio were 230.68 °C, 30 min, and 20%, respectively, for the MY-HHV-AC set and 220 °C, 30 min, 20%, respectively, for the EY-AC set. The MY-HHV-AC set had properties close to those of peat and lignite. Furthermore, compared with that of the pure biochar, the AC of the two sets decreased by 15.71% and 14.88%, respectively, indicating that the prepared mixed biochars served as ideal biofuels. Finally, a circular economy framework for biobriquette fuel was proposed and prospects for preparing pellets provided.

Fuel Characteristics and Removal of AAEMs in Hydrochars Derived from Sewage Sludge and Corn Straw.

Co-hydrothermal carbonization (Co-HTC) of sewage sludge (SS) and corn straw (CS) for fuel preparation is a waste treatment method that reduces the pre-treatment cost of solid waste and biomass fuel. Based on the response surface methodology (RSM), a test was designed to prepare SS and CS hydrochars using a hydrothermal high-pressure reactor. The test examined the higher heating value (HHV) and the concentrations of alkali metals and alkaline earth metals (AAEMs) and Cl. The HHV of SS-hydrochar decreased with an increase in reaction temperature, but that of CS-hydrochar increased. The yield of CS-hydrochar was at 26.74−61.26%, substantially lower than that of SS-hydrochar. Co-hydrochar has the advantages of HHV and an acceptable yield. The HHV of co-hydrochar was 9215.51−12,083.2 kJ/kg, representing an increase of 12.6−47.6% over single component hydrochar, while the yield of co-hydrochar was 41.46−72.81%. In addition, the stabilities of AAEM and Cl in the co-hydrochar were Mg > Ca > K > Na > Cl. SS and CS had a synergistic effect on dechlorination efficiency (DE), which had a negative effect on the removal efficiency (RE) of Ca and Na. The optimal hydrocharization conditions were a temperature of approximately 246.14 °C, a residence time of approximately 90 min, and a mixing ratio of SS−CS of approximately 57.18%. The results offer a way to utilize SS and CS by Co-HTC and convert them into low-chlorine and low-alkali fuel, thus pushing the improvement of this promising waste-to-energy technology.

Association of pre-diabetes and type 2 diabetes mellitus with intracranial plaque characteristics in patients with acute ischemic stroke.

OBJECTIVES: To investigate the association of pre-diabetes(i.e., the early stages of glucometabolic disturbance) and Type 2 diabetes mellitus (T2DM) with intracranial plaque characteristics in patients with acute ischemic stroke using three-dimensional high-resolution MR imaging. METHODS: One hundred and forty-three symptomatic patients with acute ischemic stroke attribute to intracranial atherosclerotic plaque were prospectively enrolled. All participants were further divided into three groups: normal glucose metabolism(non-diabetes) group(n = 41), pre-diabetes group(n = 45), and T2DM group(n = 57) according to glucometabolic status. Culprit plaque characteristics (such as plaque burden, normalized wall index and enhancement ratio), total plaque number, and global plaque enhancement score were analyzed and compared among the three glucometabolic groups. The association between pre-diabetes and T2DM with intracranial plaque characteristics was assessed by logistic regression and multivariate linear regression. RESULTS: Plaque number was higher in patients with pre-diabetes and T2DM compared with those with non-diabetes(3.71 ± 1.83 and 3.75 ± 1.71 vs 2.24 ± 1.46, p = 0.006). Multivariate logistic regression showed a significant association of multiple intracranial plaques with pre-diabetes(OR 3.524, 95% CI 1.082 ~ 11.479, p = 0.037), T2DM(OR 3.760, 95% CI 1.098 ~ 12.872, p = 0.035) and luminal stenotic rate. Both pre-diabetes and T2DM were significantly associated with culprit plaque enhancement ratio(ß = 0.527 and ß = 0.536; respectively; p < 0.001) and global plaque enhancement score(ß = 0.264 and ß = 0.373; respectively; p < 0.05). CONCLUSIONS: Patients with pre-diabetes and T2DM had similar intracranial atherosclerotic plaque vulnerability, as demonstrated by multiple plaques, increased culprit plaque enhancement ratio and global plaque enhancement score. ADVANCES IN KNOWLEDGE: Pre-diabetes might be a risk factor for intracranial plaque vulnerability. It is necessary to monitor a slight increase in blood glucose in non-diabetes patients with acute ischemic stroke.

Impact of Spinal/Epidural Anesthesia Versus General Anesthesia on Perioperative Outcomes in Patients Undergoing Lumbar Spine Surgery: An Updated Systematic Review and Meta-analysis.

STUDY DESIGN: A systematic review and meta-analysis. OBJECTIVE: To compare impact of different anesthesia techniques on perioperative outcomes in patients undergoing lumbar spine surgery. SUMMARY OF BACKGROUND DATA: Both general anesthesia and spinal anesthesia/epidural anesthesia can be used for lumbar spine surgery. There is still much controversy that which anesthesia technique is much more suitable for lumbar spine surgery with less complications, general anesthesia or regional anesthesia. METHODS: A comprehensive search of the literature was conducted using Excerpta Medica database (EMBASE), PubMed, and Cochrane library for randomized controlled trials and independent reviewers assessed eligibility for included studies. Primary outcomes included incidences of intraoperative hypertension, hypotension, tachycardia, and bradycardia. Secondary outcomes included postoperative analgesic requirement, postoperative nausea and vomiting (PONV), headache, urinary retention, blood loss, and length of hospital stay. RESULTS: Ten randomized controlled trials consisting of 733 adult patients undergoing lumbar spine surgery were included. Spinal anesthesia/epidural anesthesia group had significant lower incidences of intraoperative hypertension [odds ratio (OR), 0.18; 95% confidence interval (CI), 0.08-0.38; P <0.00001; I2 =0.0%] and tachycardia (OR, 0.45; 95% CI, 0.26-0.79; P =0.006; I2 =0.0%), analgesic requirement in postanesthesia care unit (OR, 0.13; 95% CI, 0.08-0.22; P <0.00001; I2 =0.0%), PONV within 24 hours after surgery (OR, 0.27; 95% CI, 0.16-0.46; P <0.00001; I2 =6.0%), and shorter length of postoperative hospital stay (mean difference, -0.28; 95% CI, -0.37 to -0.18; P <0.00001; I2 =32.0%). There were no significant differences in incidences of intraoperative hypotension and bradycardia, PONV in postanesthesia care unit, analgesic requirement, urinary retention, and headache within 24 hours after surgery. CONCLUSIONS: Low to moderate quality of evidence revealed that patient undergoing lumbar spine surgery might benefit from spinal or epidural anesthesia.

Synthesis and anticancer activity of novel histone deacetylase inhibitors that inhibit autophagy and induce apoptosis.

The combination of histone deacetylase (HDAC) and autophagy inhibitor has been considered as a novel cancer therapeutic strategy. To find novel HDAC inhibitors that can inhibit autophagy, several new series of oxazole- and thiazole-based HDAC inhibitors were designed and synthesized by replacing the phenyl cap in SAHA with 5-phenyloxazoles and 5-phenylthiazoles. The representative oxazole derivative, compound 21, showed better enzymatic inhibitory activity than SAHA (vorinostat). Compound 21 induced G2/M cell cycle arrest and its antiproliferative activity is 10-fold better than SAHA in multiple tumor cell lines. Western blot analysis showed that compound 21 can markedly increase the acetylation levels of tubulin, histone H3, and histone H4. Contrary to SAHA, compound 21 was found to inhibit autophagy. Additionally, compound 21 induced cell apoptosis via the Bax/Bcl-2 and caspase-3 pathways. Ultimately, compound 21 exhibited higher oral antitumor potency than SAHA in a A549 xenograft model. Our results indicated that compound 21 may be further developed as a promising anticancer agent.

Bioinformatic workflow fragment discovery leveraging the social-aware knowledge graph.

Constructing a novel bioinformatic workflow by reusing and repurposing fragments crossing workflows is regarded as an error-avoiding and effort-saving strategy. Traditional techniques have been proposed to discover scientific workflow fragments leveraging their profiles and historical usages of their activities (or services). However, social relations of workflows, including relations between services and their developers have not been explored extensively. In fact, current techniques describe invoking relations between services, mostly, and they can hardly reveal implicit relations between services. To address this challenge, we propose a social-aware scientific workflow knowledge graph (S 2 KG) to capture common types of entities and various types of relations by analyzing relevant information about bioinformatic workflows and their developers recorded in repositories. Using attributes of entities such as credit and creation time, the union impact of several positive and negative links in S 2 KG is identified, to evaluate the feasibility of workflow fragment construction. To facilitate the discovery of single services, a service invoking network is extracted form S 2 KG, and service communities are constructed accordingly. A bioinformatic workflow fragment discovery mechanism based on Yen's method is developed to discover appropriate fragments with respect to certain user's requirements. Extensive experiments are conducted, where bioinformatic workflows publicly accessible at the myExperiment repository are adopted. Evaluation results show that our technique performs better than the state-of-the-art techniques in terms of the precision, recall, and F1.

Alteration of gut microbiota in high-fat diet-induced obese mice using carnosic acid from rosemary.

Rosmarinus officinalis (rosemary) is widely used as a food ingredient. Rosemary extract (containing 40% carnosic acid) exhibited potent antiobesity activity. However, the relationship between carnosic acid (CA) and changes in the gut microbiota of high-fat diet (HFD)-induced obese mice has not been fully investigated. C57BL/6 mice were fed a normal diet, an HFD, or an HFD containing 0.1% or 0.2% CA for 10 weeks. CA exhibited promising antiobesity effects and caused marked alterations in the gut microbiota of HFD-induced obese mice. CA caused the prevalence of probiotics and functional bacteria, including Akkermansia muciniphila, Muribaculaceae unclassified, and Clostridium innocuum group, and inhibited diabetes-sensitive bacteria, including Proteobacteria and Firmicutes. The ratio of Firmicutes to Bacteroidetes was regulated by CA in a dose-dependent manner, decreasing it from 13.22% to 2.42%. Additionally, CA reduced bile acid-metabolizing bacteria, such as Bilophila, Clostridium, Lactobacillus, and Leuconostoc. The results of the linear discriminant analysis and effect size analysis indicated that CA attenuated the microbial changes caused by HFD. The high CA (HCA) group (HFD containing 0.2% CA) exhibited a greater abundance of Verrucomicrobiae (including Akkermansia muciniphila, genus Akkermansia, family Akkermansiaceae, and order Verrucomicrobiales), Eubacterium, and Erysipelatoclostridium, and the low CA (LCA) group (HFD containing 0.1% CA) exhibited a greater abundance of Eisenbergiella, Intestinimonas, and Ruminococcaceae. Our results demonstrate that the antiobesity effects of CA might be strongly related to its prebiotic effects.

Indole-substituted flavonol-based cysteine fluorescence sensing and subsequent precisely controlled linear CO liberation.

The first water-soluble B-ring-indole-substituted flavonol-based cysteine (Cys) fluorescent probe, MICA (2-(1-methyl-1H-indol-3-yl)-4-oxo-4H-chromen-3-yl-acrylate), was developed, which simultaneously serves as a precursor of photoCORM. In PBS buffer (only 15% DMF), MICA can perform rapid (330 s), highly chemoselective (particularly for homocysteine and glutathione) and sensitive (limit of detection: 92 nM) sensing and visualization of exogenous and endogenous Cys in live HeLa cells and zebrafish over a wide linear concentration range (0-12 µM/2.4 equiv.). The fluorophore HMIC (3-hydroxy-2-(1-methyl-1H-indol-3-yl)-4H-chromen-4-one), actuated and quantitatively generated via the sensing reaction of the precursor MICA with Cys, was designed as a photoCORM. By modulating the light illumination intensity or illumination duration or photoCORM dosage, HMIC can provide precisely controlled quantitative and linear CO gas by visible light illumination in aerobic environments. For live HeLa cells, MICA and all reaction products showed low toxicity (over 85% cell viability versus 10 µM analyst) and efficient cellular uptake. In live HeLa cells and zebrafish, both exogenous and endogenous Cys can be visualized by MICA, and the location and CO liberation process of the generated HMIC can be tracked in real time through its fluorescence. Substitution of the B-ring of 3-hydroxy-flavone (3-FL) by indole results in a 52 nm absorption red-shift vs.3-FL. Our work is the first water-soluble B-ring-indole-substituted flavonol-based fluorescent probe that efficaciously detects and visualizes exogenous and endogenous Cys both in vitro and in vivo, simultaneously serving as a precursor of photoCORM, actuated by Cys and triggered by visible light, releasing linear CO in aerobic environments. This work not only provides promising applications for the detection and visualization of exogenous and endogenous Cys, and spatiotemporally controllable CO liberation in live systems, but will also facilitate the development of handy molecular tools for clinical diagnosis and CO gas therapy.

Vertebral column resection (VCR) at the subapical vertebra for correction of angular kyphosis associated with neurofibromatosis type 1(NF1): a case report.

PURPOSE: To describe the process and outcome of vertebral column resection (VCR) at the subapical vertebra for correction of angular kyphosis associated with neurofibromatosis type 1(NF1). METHODS: A review and summary of the medical history, radiographs, operative procedure, and complications of a 16-year-old male presenting with severe angular kyphosis associated with NF1 with dyspnea. RESULTS: A 16-year-old male presented with severe angular kyphosis associated with NF1 with dyspnea. Preoperative radiographs demonstrated multiple vertebrae were rotated in the vicinity of the apical vertebra, with a wedge-shaped deformity, dysplasia, T10-T12 kyphotic angle of 160°, and T2-L2 kyphotic angle of 95°. VCR at the L1 vertebra (distal end of the apical vertebra) with bone grafting and internal fixation was performed. Postoperative imaging revealed that the T2-L2 Cobb angle was 20°, denoting a correction rate of 79%. The patient's height increased from 130 to 150 cm. The position of internal fixation was not displaced, and the correction angle was maintained at 2-year follow-up. CONCLUSIONS: The novel strategy of performing VCR at the subapical vertebra, with posterior displacement of the distal end, and remodeling of the spinal canal is potentially a safe and efficacious option to correct sharp angular kyphosis.

Bidirectional interaction of nobiletin and gut microbiota in mice fed with a high-fat diet.

Nobiletin is abundant in citrus peels and demonstrates good anti-obesity bioactivity. However, its anti-obesity mechanisms still remain unclear. This study aims to explore the bidirectional interaction between nobiletin and gut microbiota in mice fed with a high-fat diet. For the colonic bioconversion, more demethylated metabolites with higher biological activity were found in feces than nobiletin in the 48 h excretion study and 8 week consecutive dosing study. Moreover, long-term oral intake of nobiletin would modify the gut microbiota with improved demethylation ability and enhanced production of short chain fatty acids. The comparison of metabolite profiles in mouse liver and feces indicated that gut microbiota might have a higher biotransformation activity on nobiletin than the host. Two bacteria at the genus level, Allobaculum and Roseburia, remained enriched by nobiletin after the 4- and 8-week feedings. They might correlate with the enhanced nobiletin biotransformation and actively contribute to the health benefits of nobiletin in vivo. These results suggested that the bidirectional interaction of nobiletin and gut microbiota played an important role on the anti-obesity effect of nobiletin.